PMID- 8250521
TI  - [Differentiation of human colon cancer cells: a new approach to cancer of the
      colon].
AB  - Our purpose is to demonstrate that some human colon cancer cells are able to
      express the same differentiation features as normal intestinal epithelial cells
      and to report experimental data which suggest that these particular cells are
      spontaneously resistant and adaptable to anticancer drugs. The concept of normal
      differentiation of colon cancer cells is supported by observations made with two
      cultured cell lines, Caco-2 and HT-29. The cell line Caco-2 expresses
      spontaneously and homogeneously an enterocytic differentiation. The cell line HT
      29 is heterogeneous as it contains a small proportion (< 5%) of differentiated
      cells of either enterocytic or mucus-secreting type. Homogeneous populations of
      differentiated HT-29 cells of either type have been isolated by pressure
      selection. In order to investigate whether the pressure associated with anti
      cancer drugs would result in the selection of differentiated populations, HT-29
      cells were cultured in the presence of increasing concentrations of methotrexate
      and 5-fluorouracil. The resulting resistant populations were found to be totally
      differentiated. This supports the view that the small proportion of parental
      cells which are able to differentiate are also able to spontaneously resist to
      drug pressure. These results imply that the concept of cellular differentiation
      should be considered by pathologists. They also imply that basic research should
      be developed in order to unravel which mechanisms of drug resistance are
      specifically associated with the ability of the cells to differentiate.

PMID- 8250522
TI  - [30 years' work on congenital glucose and galactose malabsorption: from phenotype
      to genotype].
AB  - Intestinal absorption of glucose plays a key role in water economy as attested by
      the congenital and selective glucose and galactose malabsorption which is
      expressed as severe watery diarrhea just after birth, leading to life-threatening
      dehydration. This syndrome, transmitted on an autosomal recessive mode, is the
      consequence of a functional defect of the glucose-sodium cotransporter at the
      luminal membrane of the enterocyte of the small intestine. In one family, this
      defect was associated with a misense mutation at position 92 of the SGLT1 gene
      coding for the cotransporter. The mutant RNA reproduced the transport defect
      after injection in xenopus oocytes. These results confirm the genetic origin of
      the congenital defect; in addition they indicate that the study of the
      relationship between phenotype and genotype of congenital defects of intestinal
      transport may help in the understanding of basic intestinal functions in relation
      with human nutrition.

PMID- 8250523
TI  - Expanded clinical trials of treatments for multiple sclerosis. The Advisory
      Committee on Clinical Trials of New Agents in Multiple Sclerosis of The National
      Multiple Sclerosis Society.

PMID- 8250524
TI  - Molecular genetics in neurology.
AB  - There has been remarkable progress in the identification of mutations in genes
      that cause inherited neurological disorders. Abnormalities in the genes for
      Huntington disease, neurofibromatosis types 1 and 2, one form of familial
      amyotrophic lateral sclerosis, fragile X syndrome, myotonic dystrophy, Kennedy
      syndrome, Menkes disease, and several forms of retinitis pigmentosa have been
      elucidated. Rare disorders of neuronal migration such as Kallmann syndrome,
      Miller-Dieker syndrome, and Norrie disease have been shown to be due to specific
      gene defects. Several muscle disorders characterized by abnormal membrane
      excitability have been defined as mutations of the muscle sodium or chloride
      channels. These advances provide opportunity for accurate molecular diagnosis of
      at-risk individuals and are the harbinger of new approaches to therapy of these
      diseases.

PMID- 8250525
TI  - Characteristics of medial temporal lobe epilepsy: I. Results of history and
      physical examination.
AB  - In order to more precisely define a syndrome of medial temporal lobe epilepsy,
      histories and physical findings were evaluated in 67 patients studied with
      intracranial electrodes who had medial temporal seizure onset and became seizure
      free following temporal lobectomy. Patients with circumscribed, potentially
      epileptogenic mass lesions were excluded. Fifty-four patients (81%) had histories
      of convulsions during early childhood or infancy, 52 of which were associated
      with fever. Complicated febrile seizures occurred in 33 (94%) of the 35 patients
      in whom detailed descriptions of the febrile seizures were available. Bacterial
      (5) or viral (2) central central nervous system infections were present in 7
      patients with seizures and fevers. Other less common, but probably significant,
      risk factors included head trauma (10%) and birth trauma (3%). Only 5 patients
      had no apparent risk factors. The mean age at habitual seizure onset was 9 years.
      All patients had complex partial seizures, with half having only complex partial
      seizures. The other half also had secondarily generalized tonic-clonic seizures,
      but these were never the predominant seizure type. Only 3 patients had histories
      of convulsive status epilepticus and no patient had a history of nonconvulsive
      status epilepticus. All but 3 patients reported auras before some or all of their
      seizures, with an abdominal visceral sensation being by far the most common type
      of aura (61%). Of the 60 patients with identified risk factors, all but 2 had an
      interval between the presumed cerebral insult and the development of habitual
      seizures, with a mean seizure-free interval of 7.5 years.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8250526
TI  - Characteristics of medial temporal lobe epilepsy: II. Interictal and ictal scalp
      electroencephalography, neuropsychological testing, neuroimaging, surgical
      results, and pathology.
AB  - Sixty-seven patients with temporal lobe epilepsy without circumscribed,
      potentially epileptogenic lesions, who were studied with intracranial electrodes
      and who became seizure free following temporal lobectomy were retrospectively
      evaluated with regard to preoperative scalp electroencephalographic (EEG)
      findings, neuropsychological test results, neuroimaging findings, results of
      surgery, and pathology of resected tissue. Interictal scalp EEG showed paroxysmal
      abnormalities during prolonged monitoring in 64 patients (96%). These were
      localized in the anterior temporal region in 60 (94%) of these 64 patients.
      Bilateral independent paroxysmal activity occurred in 42% of the patients and was
      preponderant over the side of seizure origin in half. Ictal EEG changes were
      rarely detected at the time of clinical seizure onset, but lateralized buildup of
      rhythmic seizure activity during the seizure occurred in 80% of patients. In 13%,
      the scalp EEG seizure buildup was, however, contralateral to the side of seizure
      origin as subsequently determined by depth EEG and curative surgery. Lateralized
      postictal slowing, when present, was a very reliable lateralizing finding.
      Neuropsychological testing provided lateralizing findings concordant with the
      side of seizure origin in 73% of patients. When neuropsychological testing
      produced discordant results or nonlateralizing findings, those patients were
      usually found to have right temporal seizure origin. Intracarotid amobarbital
      (Amytal) testing demonstrated absent or marginal memory functions on the side of
      seizure onset in 63% of patients, but 26 patients (37%) had bilaterally intact
      memory. In those patients who had magnetic resonance imaging, it was very
      sensitive in detecting subtle medial temporal abnormalities. These abnormalities
      were present in 23 of 28 magnetic resonance images, and corresponded with mesial
      temporal sclerosis on pathological examination in all but 2 patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8250527
TI  - Neuron loss localizes human temporal lobe epilepsy by in vivo proton magnetic
      resonance spectroscopic imaging.
AB  - Temporal lobe epileptogenic foci were blindly localized in 8 patients with
      medically refractory unilateral complex partial seizures using noninvasive in
      vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) with 4-ml
      effective voxel size. The brain proton metabolite signals in 8 matched normal
      controls were bilaterally symmetrical within +/- 10%. The hippocampal seizure
      foci had 21 +/- 5% less N-acetyl aspartate signal than the contralateral
      hippocampal formations (p < 0.01). The focal N-acetyl aspartate reductions were
      consistent with pathology findings of mesial temporal sclerosis with selective
      neuron loss and gliosis in the surgically resected epileptogenic foci. Proton
      MRSI correctly localized the seizure focus in all 8 cases. By comparison, MR
      imaging correctly localized 7 of 8 cases and single photon emission computed
      tomography correctly localized 2 of 5 cases. No lactate was detected in these
      interictal studies. No significant changes in choline or creatine were observed.
      In conclusion, 1H-MRSI is a useful tool for the noninvasive clinical assessment
      of intractable focal epilepsy. These preliminary results suggest that 1H-MRSI can
      accurately localize temporal lobe epileptogenic foci.

PMID- 8250528
TI  - Atrophy of mesial structures in patients with temporal lobe epilepsy: cause or
      consequence of repeated seizures?
AB  - We studied 70 epileptic patients by using magnetic resonance imaging volumetric
      measurements of amygdala (AM) and hippocampal formation (HF). Fifty patients
      presented with intractable temporal lobe epilepsy (TLE), 10 patients had focal
      extratemporal lobe epilepsy, and 10 had generalized epilepsy. In 91% of the 45
      TLE patients without foreign tissue lesions, there was significant smallness of
      the AM and/or HF coinciding with the side of electroencephalographic seizure
      onset. No significant smallness or asymmetry was demonstrated in patients with
      focal extratemporal or generalized epilepsy. We performed a linear regression
      analysis, plotting the number of years of recurrent seizures and the estimated
      seizure frequency against the volumes of the AM and HF. There was no correlation
      between either of these two parameters and AM or HF volume (p > 0.9). There was
      also no correlation between the patient's age and volumetric measurements of AM
      or HF, nor did these measurements correlate with the occurrence of generalized
      seizures. On the other hand, patients with antecedent prolonged febrile
      convulsions in early childhood had significantly smaller AM and HF, compared with
      those without such a history (p < 0.001). The findings indicate that repeated
      seizures or longer duration of epilepsy do not cause increased atrophy of AM or
      HF that is measurable by volumetric magnetic resonance imaging.

PMID- 8250529
TI  - A new inherited prion disease (PrP-P105L mutation) showing spastic paraparesis.
AB  - We report the clinicopathological findings of 5 patients with an inherited prion
      disease with a codon 105 (Pro to Leu) mutation. All of the patients had a spastic
      gait disturbance and progressive dementia without either cerebellar signs,
      myoclonus, or periodic synchronous discharges. Autopsy of 3 patients revealed
      numerous amyloid plaques in the cerebral cortex, especially in the motor cortex
      and the frontal lobe where neuronal loss and severe gliosis were observed in the
      absence of spongiform changes. The cerebellum was preserved histologically except
      for only a few amyloid plaques. The pyramidal tracts in the brainstem and spinal
      cord showed vacuolated changes and a loss of myelin, but no prion protein
      accumulations. Thus, the prion protein codon 105 mutation is considered to
      correspond to a new variant of the Gerstmann-Straussler syndrome with spastic
      paraparesis.

PMID- 8250530
TI  - Site of autonomic deficit in harlequin syndrome: local autonomic failure
      affecting the arm and the face.
AB  - The site of autonomic deficit was investigated in 4 patients with loss of
      thermoregulatory flushing and sweating on one side of the face but no associated
      miosis (harlequin syndrome). In 2 patients the sudomotor deficit included the
      hand. Signs of postganglionic sympathetic deficit included pathological lacrimal
      sweating (2 patients) and supersensitivity to 1% phenylephrine eyedrops (3
      patients). One or both pupils constricted excessively to 0.0625% pilocarpine
      eyedrops (3 patients), consistent with ocular parasympathetic deficit. These
      findings suggest that pre- or postganglionic cervical sympathetic fibers, and
      parasympathetic neurons in the ciliary ganglia, are compromised in harlequin
      syndrome. The finding of cholinergic supersensitivity in the iris muscles of
      patients with harlequin syndrome indicates a relationship with Holmes-Adie
      syndrome, Ross's syndrome, and the persistent autonomic deficit occasionally
      associated with Guillain-Barre syndrome.

PMID- 8250531
TI  - A 10-year experience with postpump chorea.
AB  - Postpump chorea (PPC) is the development of choreoathetoid movements within 2
      weeks following cardiopulmonary bypass. Over a 10-year period, 668 children
      underwent open cardiac surgery, of whom 8 (1.2%) developed PPC. Age at surgery
      ranged from 8 to 34 months. The onset of chorea was 3 to 12 days following
      surgery. Computed tomography and magnetic resonance imaging showed atrophy but no
      focal lesions. Cerebral positron emission tomography using
      [18F]fluorodeoxyglucose in a patient following 12 months of chorea showed patchy
      areas of decreased glucose metabolism. None of the patients were developmentally
      normal 22 to 130 months following surgery. Three patients have had transient and
      5 have persistent chorea. Neurological deficits ranged from a mild learning
      disability to progressive hypotonia and obtundation ending in death. One of 4
      patients who received haloperidol had a decrease in the severity of chorea. We
      compared PPC patients with 39 randomly selected controls. During surgery,
      affected patients spent significantly more time on pump and at temperatures under
      36 degrees C, were cooled to lower temperatures than controls, and were more
      likely to have had a circulatory arrest. One patient developed chorea without a
      history of circulatory arrest. We conclude that (1) there is a strong association
      between PPC, deep hypothermia, and circulatory arrest, (2) absence of
      characteristic macroscopic changes suggests a biochemical or microembolic
      etiology in some cases, (3) chorea is frequently associated with developmental
      delay, and (4) the prognosis for complete resolution of chorea is guarded.

PMID- 8250532
TI  - The mutation at nt 8993 of mitochondrial DNA is a common cause of Leigh's
      syndrome.
AB  - Twelve patients with Leigh's syndrome from 10 families harbored a T > G point
      mutation at nt 8993 of mtDNA. This mutation, initially associated with neurogenic
      weakness, ataxia, and retinitis pigmentosa, was later found to result in the
      Leigh phenotype when present in a high percentage. In our patients, the mutation
      was heteroplasmic, maternally inherited, and appeared to segregate rapidly within
      the pedigrees. Quantitative analysis revealed a good correlation between
      percentage of mutant mitochondrial genomes and severity of the clinical
      phenotype. The mutation was not found in > 200 patients with other mitochondrial
      encephalomyopathies or in controls. Mitochondrial enzyme activities were normal
      in all but 1 patient, and there were no ragged-red fibers in the muscle biopsy.
      Lactic acidosis was present in 92% of patients. Our findings suggest that the
      mtDNA nt 8993 mutation is a relatively common cause of Leigh's syndrome.

PMID- 8250533
TI  - Electroclinical signs of benign neonatal familial convulsions.
AB  - Benign neonatal familial convulsions comprise a distinct epileptic syndrome with
      an autosomal mode of transmission. The electroclinical signs of seizures in this
      syndrome are not yet well defined. In 3 children from two families presenting
      with benign neonatal familial convulsions, 14 seizures were recorded during
      electroencephalographic (EEG)-video sessions. All seizures occurred during sleep,
      after a short arousal reaction. Seizures started with bilateral, symmetrical
      flattening of the EEG for 5 to 19 seconds; simultaneously there was apnea and
      tonic motor activity. The EEG flattening was followed by a long (1-2-minute)
      bilateral discharge of spikes and sharp waves; simultaneously, there were
      vocalizations, chewing, and focal or generalized clonic activity. The prominence
      of EEG and motor abnormalities varied between the left and the right from one
      seizure to the next in any given child. The seizures stopped without EEG or
      clinical postictal depression. These electroclinical observations suggest that
      the convulsions of benign neonatal familial convulsions are a form of generalized
      tonic-clonic seizure whose expression may be asymmetrical, probably because of
      the immaturity of the corpus callosum or other structures ensuring seizure
      synchronization.

PMID- 8250534
TI  - Familial parkinsonism with depression: a clinicopathological study.
AB  - A family with autosomal dominant inheritance of an early-onset and rapidly
      progressive parkinsonian syndrome and associated severe depression is reported.
      Three members had parkinsonism with depression, 3 had parkinsonism alone, and 2
      suffered depression only. Pathological brain examination in 2 members with
      parkinsonism and depression revealed distinctive changes, with devastation of the
      substantia nigra, scarce Lewy bodies, and gliosis of the caudate nucleus and
      globus pallidus. The clinical and pathological findings were similar to those in
      four previously described families with autosomal dominant parkinsonism,
      depression, and alveolar hypoventilation.

PMID- 8250535
TI  - Serum antibodies to Purkinje cells and dorsal root ganglia neurons in sensory
      neuronopathy without malignancy.
AB  - Anti-Purkinje cell antibodies (APCA), believed to be markers of paraneoplastic
      cerebellar degeneration in females, have been identified in the serum of 3 men
      with subacute sensory neuronopathies and no evidence of tumors 5 years after the
      onset of the neurological signs. By indirect immunohistochemistry on sections of
      rat cerebellum and dorsal root ganglia, the patients' IgG bound to the cytoplasms
      of both Purkinje cells and dorsal root ganglia neurons. By western blot analysis
      on whole human cerebellum and whole human dorsal root ganglia homogenates, the
      IgG from 2 patients bound to a 62-kd protein in both homogenates and the IgG from
      1 patient bound to a 110-kd protein in the cerebellum homogenate only. Yo
      autoantibody test was negative in all patients. Our study provides evidence that
      non-anti-Yo APCA may be associated with subacute sensory neuronopathies and are
      not necessarily markers of an underlying tumor. The previously described anti-Yo
      APCA has only occurred in females with cancer.

PMID- 8250536
TI  - The gp120 glycoprotein of human immunodeficiency virus type 1 binds to sensory
      ganglion neurons.
AB  - Using immunofluorescence microscopy we found that gp120 binds to the surface of
      rat dorsal root ganglia neurons and human neuroblastoma cells but not to rat
      fibroblasts or glial cells. The binding of gp120 to neurons was eliminated by
      pretreatment with trypsin, which removes cell-surface proteins, but not with
      chloroform: methanol, which removes glycolipids. As control, neuronal staining by
      antisulfatide antibodies was eliminated by pretreatment with chloroform: methanol
      but not with trypsin. The gp120 binding to neurons was also inhibited by the
      mouse monoclonal antibody 01, which binds to galactocerebroside and cross
      reactive glycoproteins. These studies suggest that the receptor for gp120 on the
      surface of the dorsal root ganglia neurons is a glycoprotein. This interaction
      may mediate the effects of human immunodeficiency virus type 1 in sensory
      neuropathy.

PMID- 8250537
TI  - Parvalbumin-immunoreactive cortical neurons in Creutzfeldt-Jakob disease.
AB  - Massive abnormalities of parvalbumin-immunoreactive cortical neurons were
      observed in the cerebral biopsy samples of 3 patients with Creutzfeldt-Jakob
      disease. Immunoreactive cells had reduced and short, often fragmented, dendrites,
      and large numbers of dendritic varicosities were observed. Since parvalbumin
      immunoreactive neurons are the most important inhibitory cells in the cerebral
      cortex, the damage to these neurons may account, in part, for the impaired
      cortical function, and may play a role in the appearance of myoclonus and
      electroencephalographic patterns in patients with Creutzfeldt-Jakob disease.

PMID- 8250538
TI  - Demonstration of human T-cell lymphotropic virus type I (HTLV-I) from an HTLV-I
      seronegative south Indian patient with chronic, progressive spastic paraparesis.
AB  - Here we describe a human T-cell lymphotropic virus type I (HTLV-I) seronegative
      patient from South India with a chronic, progressive spastic paraparesis from
      which HTLV-I has been isolated from peripheral blood lymphocytes. HTLV-I pol and
      tax viral sequences were detected in DNA from fresh peripheral blood lymphocytes
      (PBL) by polymerase chain reaction (PCR) and liquid hybridization techniques.
      Southern blot analysis of the PCR products demonstrated a low copy number of HTLV
      I at the level of one viral copy per 10,000 fresh PBL. A long-term CD4+ T-cell
      line was established from PBL of this patient using recombinant interleukin-2,
      OKT3, and feeder cells. DNA from these cultured lines was amplified and portions
      of the HTLV-I long terminal repeat (U3), pol, env, and tax regions were sequenced
      (a total of 1,115 bp). The sequence data showed that the HTLV-I associated with
      this patient was 98.8% homologous to prototype HTLV-I. Southern blot analysis
      also confirmed the presence of full-length HTLV-I. These results indicate that
      HTLV-I can be demonstrated in an HTLV-I seronegative patient from South India
      with a chronic progressive neurological disorder.

PMID- 8250539
TI  - Large focal tumor-like demyelinating lesions of the brain.

PMID- 8250540
TI  - Transient inhibition of foot-and-mouth disease virus infection of BHK-21 cells by
      antisense oligonucleotides directed against the second functional initiator AUG.
AB  - The antiviral activity of antisense oligonucleotides corresponding to different
      regions of foot-and-mouth disease virus (FMDV) genome has been assessed in BHK-21
      cells. The locations of the oligonucleotides used were: (i) two regions within
      the internal ribosome entry site (IRES), involved in the regulation of the
      translation initiation of the viral polyprotein; (ii) each of the two functional
      initiator AUGs; (iii) an internal sequence of P2A gene; and (iv) a region at the
      3' end non-coding region. Cytoplasmic microinjection of oligodeoxyribonucleotides
      and oligoribonucleotides complementary to the second AUG resulted in a transient
      inhibition of viral VP1 expression in infected cells. Significant inhibitions,
      ranging from 35 to 52%, were obtained at 5 h post-infection using oligonucleotide
      concentrations of 125 microM and higher. The extent and duration of this
      inhibition seemed to be mediated by both a rapid transport to the nucleus and the
      short half-life of the oligonucleotide. This inhibition of FMDV protein synthesis
      was correlated with a reduction of virus yield of about 50%, as observed after
      the addition to the cell culture of an oligodeoxyribonucleotide phosphorothioate
      complementary to the second AUG.

PMID- 8250541
TI  - Synergistic anti-HSV effect of tumor necrosis factor alpha and interferon gamma
      in human corneal fibroblasts is associated with interferon beta induction.
AB  - HSV-1 (17) replicated to high titer in human corneal fibroblasts (> 10(8)
      PFU/10(5) cells) following infection at one PFU per 100 cells. Pretreatment of
      the cells for 24 h with 50 U/ml recombinant human tumor necrosis factor alpha
      (TNF-alpha) or 5 IU/ml of human interferon gamma (IFN-gamma) resulted in only
      modest reduction (2- to 19-fold) in virus yield. However, when the two cytokines
      were combined the antiviral effect was dramatically increased. There was > 1000
      fold reduction in virus titer in 8 of 8 trials. In contrast, the combinations of
      50 U/ml TNF-alpha with 5 IU/ml IFN-alpha or IFN-beta did not produce a
      synergistic effect. The pronounced synergistic antiviral activity of TNF
      alpha+IFN-gamma could be demonstrated in fibroblast cultures from different
      donors, and HSV-2 as well as HSV-1 strains were inhibited. There was no evidence
      that dual cytokine treatment was toxic for uninfected or HSV-infected cells.
      Insight into the mechanism responsible for the synergistic effect was provided by
      the observation that TNF-alpha+IFN-gamma induced IFN-beta. In addition, anti-IFN
      beta but not anti-IFN-alpha antibodies could reverse the antiviral effect, and
      reconstitution with IFN-beta could duplicate the phenomenon. We conclude that the
      combination of TNF-alpha and IFN-gamma at low concentrations can exert a powerful
      anti-herpes effect in human corneal fibroblasts which can be chiefly attributed
      to the induction of IFN-beta.

PMID- 8250542
TI  - Modulatory effect of N-acetyl-L-cysteine on the HIV-1 multiplication in
      chronically and acutely infected cell lines.
AB  - N-acetyl-L-cysteine (NAC) is known to antagonize the PMA- or cytokine-stimulated
      HIV-1 replication in latently and acutely infected monocytic and lymphocytic cell
      lines, and to reduce the virus multiplication in acutely infected, PHA-stimulated
      PBMC. We here report on the modulatory effects of NAC on the HIV-1 multiplication
      in both chronically and acutely infected lymphocytes that produce high virus
      levels independently from cytokine activation. In both cases, NAC doses of 0.12
      and 0.25 mM decreased, whereas doses of 0.5-2 mM increased the infectious HIV-1
      yield. At these concentrations, the modulatory effect of NAC on the HIV-1
      multiplication paralleled that on cell proliferation, suggesting a close
      correlation between the two phenomena; in fact, under conditions where NAC could
      not modulate the cell growth, the drug also failed to modulate the HIV-1
      multiplication. High NAC concentrations (4-16 mM), which were able to increase
      the proliferative rate of both chronically infected H9/IIIB and normal T
      lymphocytes, increased up to 6-fold the virus multiplication in H9/IIIB cells but
      were inhibitory to HIV-1 in acutely infected cells. This inhibition was due to
      the fact that, like dextran sulfate, NAC interfered with an early event in the
      virus growth cycle. The finding that high NAC doses were also capable of
      preventing syncytium formation in H9/IIIB and C8166 (or MT-4) cocultures further
      indicated an interference of the drug with receptor-binding-related events.

PMID- 8250543
TI  - Molecular approaches for the treatment of hemorrhagic fever virus infections.
AB  - Viruses causing hemorrhagic fevers in man belong to the following virus groups:
      togavirus (Chikungunya), flavivirus (dengue, yellow fever, Kyasanur Forest
      disease, Omsk hemorrhagic fever), arenavirus (Argentinian hemorrhagic fever,
      Bolivian hemorrhagic fever, Lassa fever), filovirus (Ebola, Marburg), phlebovirus
      (Rift Valley fever), nairovirus (Crimian-Congo hemorrhagic fever) and hantavirus
      (hemorrhagic fever with renal syndrome, nephropathic epidemia). Hemorrhagic fever
      virus infections can be approached by different therapeutic strategies: (i)
      vaccination; (ii) administration of high-titered antibodies; and (iii) treatment
      with antiviral drugs. Depending on the molecular target of their interaction,
      antiviral agents could be classified as follows: IMP dehydrogenase inhibitors
      (i.e., ribavirin and its derivatives); OMP decarboxylase inhibitors (i.e.,
      pyrazofurin); CTP synthetase inhibitors (i.e., cyclopentylcytosine and
      cyclopentenylcytosine); SAH hydrolase inhibitors (i.e., neplanocin A);
      polyanionic substances (i.e., sulfated polymers); interferon and
      immunomodulators.

PMID- 8250544
TI  - Selective inhibition of cytomegaloviruses by 9-(3'-ethylphosphono-1'
      hydroxymethyl-1'-propyloxy-methyl)g uanine.
AB  - 9-(3'-ethylphosphono-1'-hydroxymethyl-1'-propyloxy-methyl)gu anine (SR 3727A) was
      significantly inhibitory to strain AD169 of human cytomegalovirus (HCMV)
      utilizing plaque reduction and inhibition of intra- and extracellular virus yield
      in MRC-5 cells. The 50% effective concentrations (EC50) ranged from 6-17 microM
      for three laboratory strains of HCMV, whereas the 50% cytotoxic doses were > 4200
      microM as determined by viable cell assay and inhibition of radiolabeled
      precursors into DNA, RNA and protein. EC50 values against ganciclovir-sensitive
      clinical isolates ranged from 8-47 microM. Against two ganciclovir-resistant
      strains of HCMV, EC50 values of SR 3727A were 84 and 320 microM; against murine
      CMV (MCMV); 17 microM and against guinea pig CMV, 56 microM. SR 3727A was most
      effective when infected cells were treated 24 h or less after virus adsorption.
      BALB/c mice infected intraperitoneally (i.p.) with a lethal dose of MCMV were
      treated i.p. with 31.3, 62.5, 125, or 250 mg/kg/day of SR 3727 twice daily for 5
      days beginning 4 h pre-virus inoculation. All doses were well tolerated; the 125
      and 250 mg/kg/day doses significantly prevented death. In a second experiment, SR
      3727 at 125 mg/kg/day markedly reduced titers of recoverable virus from spleens,
      kidneys, and salivary glands harvested at varying times after virus inoculation.

PMID- 8250546
TI  - Detection of hepatitis A virus in sewage sludge by antigen capture polymerase
      chain reaction.
AB  - Antigen capture polymerase chain reaction (PCR) was tested as a sensitive and
      rapid method for detecting hepatitis A virus (HAV) in raw sewage sludge. The
      antigen capture PCR was performed both with and without solid-phase virus
      catching monoclonal antibodies. Similar results proved that both methods were
      equally sensitive. Sewage sludge samples from different regions in Germany were
      examined for evidence of HAV contamination by antigen capture PCR. This method of
      detection was compared with that used in a previous study of these sewage sludge
      samples, in which the HAV was detected through indirect immunofluorescence after
      cell culture inoculation. The results obtained by antigen capture PCR matched
      those obtained in the earlier cell culture investigations, when HAV was detected
      in raw as well as digested sewage sludge samples. The advantage of the PCR
      method, however, lies in the fact that it needs only two days while the cell
      culture propagation of HAV takes about 8 to 10 weeks.

PMID- 8250545
TI  - The use of baculoviruses as expression vectors.
AB  - The use of recombinant baculoviruses as high level expression systems is becoming
      more and more popular. This review aims to provide a summary of the impact of
      this expression system in biochemistry and biotechnology, highlighting important
      advances that have been made utilizing the system. The potential of newly
      developed multiple baculovirus expression systems to enable the reconstruction of
      complex biological molecules and processes is also reviewed.

PMID- 8250547
TI  - Bacterial aerosol emission rates from municipal wastewater aeration tanks.
AB  - In this report we describe the results of a study conducted to determine the
      rates of bacterial aerosol emission from the surfaces of the aeration tanks of
      the Metropolitan Water Reclamation District of Greater Chicago John E. Egan Water
      Reclamation Plant. This study was accomplished by conducting test runs in which
      Andersen six-stage viable samplers were used to collect bacterial aerosol samples
      inside a walled tower positioned above an aeration tank liquid surface at the
      John E. Egan Water Reclamation Plant. The samples were analyzed for standard
      plate counts (SPC), total coliforms (TC), fecal coliforms, and fecal
      streptococci. Two methods of calculation were used to estimate the bacterial
      emission rate. The first method was a conventional stack emission rate
      calculation method in which the measured air concentration of bacteria was
      multiplied by the air flow rate emanating from the aeration tanks. The second
      method was a more empirical method in which an attempt was made to measure all of
      the bacteria emanating from an isolated area (0.37 m2) of the aeration tank
      surface over time. The data from six test runs were used to determine bacterial
      emission rates by both calculation methods. As determined by the conventional
      calculation method, the average SPC emission rate was 1.61 SPC/m2/s (range, 0.66
      to 2.65 SPC/m2/s). As determined by the empirical calculation method, the average
      SPC emission rate was 2.18 SPC/m2/s (range, 1.25 to 2.66 SPC/m2/s). For TC, the
      average emission rate was 0.20 TC/m2/s (range, 0.02 to 0.40 TC/m2/s) when the
      conventional calculation method was used and 0.27 TC/m2/s (range, 0.04 to 0.53
      TC/m2/s) when the empirical calculation method was used.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8250548
TI  - Purification and characterization of a new xylanase (APX-II) from the fungus
      Aureobasidium pullulans Y-2311-1.
AB  - Aureobasidium pullulans Y-2311-1 produced four major xylanases (EC 3.2.1.8) with
      pI values of 4.0, 7.3, 7.9, and 9.4 as revealed by isoelectric focusing and
      zymogram analysis when grown for 4 days on 1.0% oat spelt xylan. The enzyme with
      a pI of 9.4 was purified by ammonium sulfate precipitation, chromatography on a
      DEAE-Sephadex A-50 column, and gel filtration with a Sephadex G-75 column. The
      enzyme had a mass of about 25 kDa as determined by both sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and gel filtration chromatography. The
      purified enzyme had a Km of 7.6 mg . ml(-1) and Vmax of 2,650 micromol . min(-1)
      . mg(-1) for birchwood xylan at 28 degrees C and pH 4.5. It lacked activity
      towards carboxymethylcellulose, cellobiose, starch, mannan, p-nitrophenyl (pNP)
      beta-D-xylopyranoside, pNP-beta-D-glucopyranoside, pNP-alpha-D-glucopyranoside,
      pNP-beta-D-cellobioside, pNP-beta-D-fucopyranoside, or pNP-alpha-D
      galactopyranoside. The predominant end products of birchwood xylan or xylohexaose
      hydrolysis were xylobiose and xylose. The enzyme had the highest activity of pH
      4.8 and 54 degrees C. Sixty percent of the activity remained after the enzyme had
      been incubated at 55 degrees C and pH 4.5 for 30 min. The sequence of the first
      68 amino acid residues at the amino terminus showed homology to those of several
      other xylonases. Immunoblot analysis with antiserum raised against the purified
      xylanase revealed that two immunologically related polypeptides of 25 and 22 kDa
      were produced in A. pullulans cultures containing oat spelt xylan or xylose as
      carbon sources but not in cultures containing glycerol or glucose.

PMID- 8250549
TI  - Molecular breeding of a biotin-hyperproducing Serratia marcescens strain.
AB  - We previously reported that an acidomycin-resistant mutant of Serratia marcescens
      Sr41, SB304, and a mutant that was derived from SB304 and was resistant to a
      higher concentration of acidomycin, SB412, produced 5 and 20 mg of D-biotin,
      respectively, per liter of a medium containing sucrose and urea (N. Sakurai, Y.
      Imai, M. Masuda, S. Komatsubara, and T. Tosa, Appl. Environ. Microbiol. 59:2857
      2863, 1993). In order to increase the productivity of D-biotin, the biotin (bio)
      operons were cloned from strains SB412, SB304, and 8000 (wild-type strain), and
      pLGM412, pLGM304, and pLGW101, respectively, were obtained through subcloning.
      These plasmids harbored 7.2-kb DNA fragments coding for the bioABFCD genes on a
      low-copy-number vector and were introduced into SB304, SB412, and 8000. Among the
      resulting recombinant strains, SB412(pLGM304) exhibited the highest D-biotin
      production (200 mg/liter) in the production medium. The plasmid was stably
      maintained in cells. Unexpectedly, SB412(pLGM412) grew very slowly, and the D
      biotin productivity of this recombinant strain was not evaluated because pLGM412
      was unstable.

PMID- 8250550
TI  - Microbial degradation of poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) in soils.
AB  - The microbial degradation of tensile test pieces made of poly(3-hydroxybutyrate)
      [P(3HB)] or a copolymer of 90% 3-hydroxybutyric acid and 10% 3-hydroxyvaleric
      acid was studied in soils incubated at a constant temperature of 15, 28, or 40
      degrees C for up to 200 days. In addition, hydrolytic degradation in sterile
      buffer at temperatures ranging from 4 to 55 degrees C was monitored for 98 days.
      Degradation was measured through loss of weight (surface erosion), molecular
      weight, and mechanical strength. While no weight loss was recorded in sterile
      buffer, samples incubated in soils were degraded at an erosion rate of 0.03 to
      0.64% weight loss per day, depending on the polymer, the soil, and the incubation
      temperature. The erosion rate was enhanced by incubation at higher temperatures,
      and in most cases the copolymer lost weight at a higher rate than the
      homopolymer. The molecular weights of samples incubated at 40 degrees C in soils
      and those incubated at 40 degrees C in sterile buffer decreased at similar rates,
      while the molecular weights of samples incubated at lower temperatures remained
      almost unaffected, indicating that molecular weight decrease is due to simple
      hydrolysis and not to the action of biodegrading microorganisms. The degradation
      resulted in loss of mechanical properties. From the samples used in the
      biodegradation studies, 295 dominant microbial strains capable of degrading P
      (3HB) and the poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer in vitro
      were isolated and identified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250551
TI  - Stimulatory effect of cooling tower biocides on amoebae.
AB  - Two species of amoebae were isolated from the cooling tower of an air
      conditioning system and examined for effects of exposure to four cooling tower
      biocides, a thiocarbamate compound, tributyltin neodecanoate mixed with
      quaternary ammonium compounds, another quaternary ammonium compound alone, and an
      isothiazolin derivative. The amoebae isolated were Acanthamoeba hatchetti and a
      Cochliopodium species. Two other amoeba cultures, an A. hatchetti culture and
      Cochliopodium bilimbosum, were obtained from the American Type Culture Collection
      (ATCC) and were also tested. The cooling tower isolates were more resistant to
      most of the biocides than the ATCC isolates were. The isothiazolin derivative was
      the least inhibitory to all four amoeba isolates, and tributyltin neodecanoate
      mixed with quaternary ammonium compounds was the most inhibitory to three of the
      four isolates. After exposure to lower concentrations of the biocides, including
      for one strain the manufacturer's recommended concentration of one biocide, the
      cooling tower amoeba populations increased significantly compared with unexposed
      controls, whereas the ATCC isolates were not stimulated at any of the
      concentrations tested. In some cases, concentrations which stimulated cooling
      tower amoebae inhibited the growth of the ATCC isolates. These results suggest
      that cooling tower amoebae may adapt to biocides, underscoring the need to use
      freshly isolated cooling tower organisms rather than organisms from culture
      collections for testing the efficacy of such biocides. The stimulatory effect of
      biocides on amoeba populations is an alarming observation, since these organisms
      may be reservoirs for legionellae. Biocides used to control microbial growth may
      actually enhance populations of host organisms for pathogenic bacteria.

PMID- 8250552
TI  - Effect of monensin on the specific activity of ammonia production by ruminal
      bacteria and disappearance of amino nitrogen from the rumen.
AB  - When unadapted mixed ruminal bacteria (312 mg of protein per liter) were treated
      with monensin (5 mM) in vitro, the rates of ammonia production from enzymatic
      digests of casein, gelatin, and soy protein (0.5 g of N per liter) were decreased
      from 46 +/- 2 to 24 +/- 1, 20 +/- 1 to 7 +/- 1, and 40 +/- 2 to 18 +/- 2 nmol/mg
      of protein per min, respectively. Monensin also caused a decrease in ammonia
      production in vivo. Nonlactating dairy cows which were fed 0.56 kg of timothy hay
      12 times per day had a steady-state ruminal ammonia concentration of 2.7 +/- 0.1
      mM, and the ammonia concentration decreased to 1.2 +/- 0.2 mM when monensin (350
      mg/day) was added to the diet. The decrease in ammonia production was associated
      with a 10-fold reduction (4.1 x 10(6) versus 4.2 x 10(5)/ml) in the most probable
      number of ammonia-producing ruminal bacteria that could use protein hydrolysate
      as an energy source. Monensin had little effect on the most probable number of
      carbohydrate-utilizing ruminal bacteria (6.5 versus 7.0 x 10(8)/ml). The addition
      of protein hydrolysates (560 g) to the rumen caused a rapid increase in the
      ammonia concentration, but this increase was at least 30% lower when the animals
      were fed monensin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250553
TI  - Reductive dehalogenation of chlorinated benzenes and toluenes under methanogenic
      conditions.
AB  - The anaerobic metabolism of chlorinated benzenes and toluenes was evaluated in
      soil slurry microcosms under methanogenic conditions. A mixture of
      hexachlorobenzene, pentachlorobenzene, and 1,2,4-trichlorobenzene (TCB) in soil
      slurries was biotransformed through sequential reductive dechlorination to
      chlorobenzene (CB). The metabolic pathway for hexachlorobenzene and
      pentachlorobenzene decay proceeded via 1,2,3,4-tetrachlorobenzene (TTCB)-->1,2,3
      TCB + 1,2,4-TCB-->1,2-dichlorobenzene (DCB) + 1,4-DCB-->CB. In a mineral salts
      medium, the CB-adapted soil microorganisms dehalogenated individual 1,2,4,5-TTCB,
      1,2,3,4-TTCB, 1,2,3-TCB, and 1,2,4-TCB but not 1,2,3,5-TTCB or 1,3,5-TCB.
      Similarly, a mixture of 2,3,6-trichlorotoluene (TCT), 2,5-dichlorotoluene (DCT),
      and 3,4-DCT was reductively dechlorinated in soil slurries to predominantly
      toluene and small amounts of 2-, 3-, and 4-chlorotoluene (CT). Toluene was
      further degraded. When tested individually in a mineral salts medium, the CT
      adapted soil microorganisms dechlorinated several TCT and DCT isomers. Key
      metabolic routes for TCTs followed: 2,3,6-TCT-->2,5-DCT-->2-CT-->toluene; 2,4,5
      TCT-->2,5-DCT + 3,4-DCT-->3-CT + 4-CT-->toluene. Among DCTs tested, 2,4-DCT and
      3,4-DCT were dechlorinated via the removal of o- and m-chlorine, respectively, to
      4-CT and subsequently to toluene via p-chlorine removal. Likewise, 2,5-DCT was
      dechlorinated via 2-CT to toluene. Evidently, microorganisms capable of removing
      o-, m-, and p-chlorines are present in the soil system, as reflected by the
      dechlorination of different isomers of CBs and CTs to CB and toluene,
      respectively. These findings help clarify the metabolic fate of chlorinated
      benzenes and toluenes in anaerobic environments.

PMID- 8250555
TI  - Mobile bacteria and transport of polynuclear aromatic hydrocarbons in porous
      media.
AB  - Sorption of hydrophobic pollutants such as polynuclear aromatic hydrocarbons
      (PAHs) to soil and aquifer materials can severely retard their mobility and the
      time course of their removal. Because mobile colloids may enhance the mobility of
      hydrophobic pollutants in porous media and indigenous bacteria are generally
      colloidal in size, bacterial isolates from soil and subsurface environments were
      tested for their ability to enhance the transport of phenanthrene, a model PAH,
      in aquifer sand. Batch isotherm experiments were performed to measure the ability
      of selected bacteria, including 14 isolates from a manufactured gas plant waste
      site, to sorb 14C-phenanthrene and to determine whether the presence of the
      suspended cells would reduce the distribution coefficient (Kd) for phenanthrene
      with the sand. Column experiments were then used to test the mobility of isolates
      that reduced the Kd for phenanthrene and to test the most mobile isolate for its
      ability to enhance the transport of phenanthrene. All of the isolates tested
      passively sorbed phenanthrene, and most but not all of the isolates reduced the
      Kd for phenanthrene. Some, but not all, of those isolates were mobile in column
      experiments. The most mobile isolate significantly enhanced the transport of
      phenanthrene in aquifer sand, reducing its retardation coefficient by 25% at a
      cell concentration of approximately 5 x 10(7) ml-1. The experimental results
      demonstrated that mobile bacteria may enhance the transport of PAHs in the
      subsurface.

PMID- 8250554
TI  - Cloning of the Aspergillus parasiticus apa-2 gene associated with the regulation
      of aflatoxin biosynthesis.
AB  - An Aspergillus parasiticus gene, designated apa-2, was identified as a regulatory
      gene associated with aflatoxin biosynthesis. The apa-2 gene was cloned on the
      basis of overproduction of pathway intermediates following transformation of
      fungal strains with cosmid DNA containing the aflatoxin biosynthetic genes nor-1
      and ver-1. Transformation of an O-methylsterigmatocystin-accumulating strain, A.
      parasiticus SRRC 2043, with a 5.5-kb HindIII-XbaI DNA fragment containing apa-2
      resulted in overproduction of all aflatoxin pathway intermediates analyzed.
      Specific enzyme activities associated with the conversion of norsolorinic acid
      and sterigmatocystin were increased approximately twofold. The apa-2 gene was
      found to complement an A. flavus afl-2 mutant strain for aflatoxin production,
      suggesting that apa-2 is functionally homologous to afl-2. Comparison of the A.
      parasiticus apa-2 gene DNA sequence with that of the A. flavus afl-2 gene (G. A.
      Payne, G. J. Nystorm, D. Bhatnagar, T. E. Cleveland, and C. P. Woloshuk, Appl.
      Environ. Microbiol. 59:156-162, 1993) showed that they shared > 95% DNA homology.
      Physical mapping of cosmid subclones placed apa-2 approximately 8 kb from ver-1.

PMID- 8250557
TI  - Rapid, automated separation of specific bacteria from lake water and sewage by
      flow cytometry and cell sorting.
AB  - The use of fluorescence-activated flow cytometric cell sorting to obtain highly
      enriched populations of viable target bacteria was investigated. Preliminary
      studies employed mixtures of Staphylococcus aureus and Escherichia coli. Cells of
      S. aureus, when mixed in different proportions with E. coli, could be selectively
      recovered at a purity in excess of 90%. This was possible even when S. aureus
      composed only approximately 0.4% of the total cells. Cell sorting was also tested
      for the ability to recover E. coli from natural lake water populations and
      sewage. The environmental samples were challenged with fluorescently labelled
      antibodies specific for E. coli prior to cell sorting. Final sample purities of
      greater than 70% were routinely achieved, as determined by CFU. Populations of E.
      coli released into environmental samples were recovered at greater than 90%
      purity. The use of flow cytometry and cell sorting to detect and recover viable
      target bacteria present at levels of less than 1% within an indigenous microflora
      was also demonstrated.

PMID- 8250556
TI  - Nutritional requirements for synthesis of heat-stable enterotoxin by Yersinia
      enterocolitica.
AB  - A defined medium that supported the growth of and synthesis of heat-stable
      enterotoxin (YST) by clinical isolates of Yersinia enterocolitica at levels
      equivalent to those observed in a complex Trypticase soy broth-0.6% yeast extract
      medium was developed. The defined medium contained four amino acids (L
      methionine, L-glutamic acid, glycine, and L-histidine), inorganic salts, N-2
      hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer, and potassium
      gluconate as the carbon source. Methionine was required for growth by most
      strains of Y. enterocolitica used in this study; thus, it was not possible to
      determine whether it was also required for the synthesis of YST. The other 17
      amino acids commonly found in proteins did not stimulate the synthesis of YST
      when added to the defined medium. The yield of YST observed with other carbon
      sources fermented by Y. enterocolitica ranged from 4- to 26-fold lower than that
      obtained with potassium gluconate. The divalent cations Ca2+ and Mn2+ had no
      effect on the synthesis of YST; however, concentrations of Fe2+ above 10 microM
      inhibited the synthesis of the enterotoxin. The addition of a mixture of
      pyrimidines containing thymine, cytosine, and uracil, each at a concentration of
      2.0 mM, stimulated the synthesis of YST by 10 to 15%, whereas a mixture of
      adenine and guanine, each at a similar concentration, inhibited the synthesis of
      YST. Vitamins had no effect on the amounts of YST produced by Y. enterocolitica
      strains grown in the defined medium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250558
TI  - Anaerobic degradation of nitrilotriacetate (NTA) in a denitrifying bacterium:
      purification and characterization of the NTA dehydrogenase-nitrate reductase
      enzyme complex.
AB  - The initial step in the anoxic metabolism of nitrilotriacetate (NTA) was
      investigated in a denitrifying member of the gamma subgroup of the
      Proteobacteria. In membrane-free cell extracts, the first step of NTA oxidation
      was catalyzed by a protein complex consisting of two enzymes, NTA dehydrogenase
      (NTADH) and nitrate reductase (NtR). The products formed were iminodiacetate and
      glyoxylate. Electrons derived from the oxidation of NTA were transferred to
      nitrate only via the artificial dye phenazine methosulfate, and nitrate was
      stoichiometrically reduced to nitrite. NTADH activity could be measured only in
      the presence of NtrR and vice versa. The NTADH-NtrR enzyme complex was purified
      and characterized. NTADH and NtrR were both alpha 2 dimers and had molecular
      weights of 170,000 and 105,000, respectively. NTADH contained covalently bound
      flavin cofactor, and NtrR contained a type b cytochrome. Optimum NTA-oxidizing
      activity was achieved at a molar ratio of NTADH to NtrR of approximately 1:1. So
      far, NTA is the only known substrate for NTADH. This is the first report of a
      redox enzyme complex catalyzing the oxidation of a substrate and concomitantly
      reducing nitrate.

PMID- 8250559
TI  - Variations in the uptake and metabolism of peptides and amino acids by mixed
      ruminal bacteria in vitro.
AB  - Mixed ruminal bacteria, isolated from sheep (Q and W) fed a concentrate and hay
      diet, were anaerobically incubated with either 14C-peptides or 14C-amino acids.
      Experiment 1 showed that uptake of both 14C-labeled substrates was rapid, but the
      rate for amino acids was twofold greater than for peptides (molecular weight,
      1,000 to 200) initially but was similar after 10 min. Experiment 2 demonstrated
      that metabolism was also rapid; at least 90% of either 14C-labeled substrate was
      metabolized by 3 min. Of the radioactivity remaining in bacteria, approximately
      30% was in the form of 14C-amino acids, but only in leucine, tyrosine, and
      phenylalanine. Supernatant radioactivity was contained only in tyrosine,
      phenylalanine, and mostly proline for incubations with 14C-amino acids but in up
      to 10 amino acids when 14C-peptides were the substrates. Short-term incubations
      (< 5 min; experiment 3) confirmed previous uptake patterns and showed that the
      experimental system was responsive to substrate competition. Experiment 4
      demonstrated that bacteria from sheep Q possessed initial and maximum rates of
      14C-amino acid uptake approximately fourfold greater (P < 0.01) than those of 14C
      peptides, but with no significant differences (P > 0.1) between four 14C-peptide
      substrate groups with molecular weights of 2,000 to < 200. By contrast, bacteria
      from sheep W showed no such distinctions (P > 0.1) between rates for 14C-peptides
      and 14C-amino acids. Calculations suggested that peptides could supply from 11 to
      35% and amino acids could supply from 36 to 68% of the N requirements of mixed
      ruminal bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250560
TI  - Growth and enrichment of pentachlorophenol-degrading microorganisms in the
      nutristat, a substrate concentration-controlled continuous culture.
AB  - The nutristat, a substrate concentration-controlled continuous culture, was used
      to grow pentachlorophenol (PCP)-degrading microorganisms. The PCP concentration
      control system consisted of on-line measurement of the PCP concentration in the
      culture vessel with a tangential filter and a flowthrough spectrophotometer. With
      PCP concentrations between 45 and 77 microM, a stable situation was established
      in the nutristat, with an average dilution rate of 0.035 +/- 0.003 h-1. Compared
      with those of fed-batch cultures and chemostat cultures, the growth rates of
      microorganisms in the PCP nutristat were significantly higher, leading to
      considerable time savings in the enrichment procedure. In addition, PCP
      accumulation to severe inhibitory levels in the culture is prevented because the
      set point determines the (maximum) PCP concentration in the culture. The use of
      the nutristat as a tool for the growth of bacteria that degrade toxic compounds
      is discussed.

PMID- 8250561
TI  - Influence of organic nutrients and cocultures on the competitive behavior of 1,2
      dichloroethane-degrading bacteria.
AB  - The effects of organic nutrients and cocultures on substrate removal by and
      competitive behavior of 1,2-dichloroethane-degrading bacteria were investigated.
      Xanthobacter autotrophicus GJ10 needed biotin for optimal growth on 1,2
      dichloroethane. In continuous culture, dilution of biotin to a concentration
      below 0.2 nM resulted in washout. Growth could be restored by inoculation with
      the 2-chloroethanol utilizer Pseudomonas sp. strain GJ1, leading to a new steady
      state in which about 1% of the mixed culture consisted of cells of strain GJ1.
      This indicates that strain GJ1 excreted biotin or a precursor for its synthesis.
      Inoculation of the mixed culture with Ancylobacter aquaticus AD25 did not result
      in washout of strain GJ10, although strain AD25 has a 10-fold-lower Ks for growth
      on 1,2-dichloroethane. Strain AD25 did not become dominant because of the lack of
      vitamins, which are necessary for its optimal growth. The results indicate that
      medium composition and the presence of other species strongly influence the
      effect of substrate limitation on the composition of a bacterial population that
      degrades a xenobiotic compound in a continuous culture.

PMID- 8250562
TI  - Modeling the growth of Enterococcus faecium in bologna sausage.
AB  - A study to set up mathematical models which allow the prediction of Enterococcus
      faecium growth in bologna sausage (mortadella) was carried out. Growth curves
      were obtained at different temperatures (5, 6, 12, 15, 25, 32, 35, 37, 42, 46,
      50, 52, and 55 degrees C). The Gompertz and logistic models, modified by
      Zwietering, were found to fit with the representation of experimental curves. The
      variations of the parameters A (i.e., the asymptotic value reached by the
      relative population during the stationary growth phase), mu m (i.e., the maximum
      specific growth rate during the exponential growth phase), and lambda (i.e., the
      lag time) with temperature were then modeled. The variation of A with temperature
      can be described by an empirical polynomial model, whereas the variation of mu m
      and lambda can be described by the Ratkowsky model modified by Zwietering and the
      Adair model, respectively. Data processing of these models has shown that the
      minimum growth temperature for E. faecium is 0.1 degrees C, the maximum growth
      temperature is 53.4 degrees C, and the optimal growth temperature is 42 to 45
      degrees C.

PMID- 8250563
TI  - Binding of small, acid-soluble spore proteins to DNA plays a significant role in
      the resistance of Bacillus subtilis spores to hydrogen peroxide.
AB  - Dormant spores of Bacillus subtilis which lack the majority of the alpha/beta
      type small, acid-soluble proteins (SASP) (termed alpha- beta- spores) that coat
      the DNA in wild-type spores are significantly more sensitive to hydrogen peroxide
      than are wild-type spores. Hydrogen peroxide treatment of alpha- beta- spores
      causes DNA strand breaks more readily than does comparable treatment of wild-type
      spores, and alpha- beta- spores, but not wild-type spores, which survive hydrogen
      peroxide treatment have acquired a significant number of mutations. The hydrogen
      peroxide resistance of wild-type spores appears to be acquired in at least two
      incremental steps during sporulation. The first increment is acquired at about
      the time of alpha/beta-type SASP synthesis, and the second increment is acquired
      approximately 2 h later, at about the time of dipicolinic acid accumulation.
      During sporulation of the alpha- beta- strain, only the second increment of
      hydrogen peroxide resistance is acquired. In contrast, sporulation mutants which
      accumulate alpha/beta-type SASP but progress no further in sporulation acquire
      only the first increment of hydrogen peroxide resistance. These findings strongly
      suggest that binding of alpha/beta-type SASP to DNA provides one increment of
      spore hydrogen peroxide resistance. Indeed, binding of alpha/beta-type SASP to
      DNA in vitro provides strong protection against cleavage of DNA by hydrogen
      peroxide.

PMID- 8250564
TI  - Metabolism of chlorinated guaiacols by a guaiacol-degrading Acinetobacter junii
      strain.
AB  - The metabolism of chlorinated guaiacols by a pure bacterial strain identified by
      its ability to use guaiacol as the sole carbon and energy source was studied.
      This strain, identified as Acinetobacter junii 5ga, was unable to grow on several
      chlorinated guaiacols and catechols. However, strain 5ga grown on guaiacol
      degraded 4- and 5-chloroguaiacol and 4,5-dichloroguaiacol. Under the same
      conditions, these cells did not degrade 6-chloroguaiacol, 4,6-dichloroguaiacol,
      4,5,6-trichloroguaiacol, or tetrachloroguaiacol, suggesting that the substitution
      at the 6 position in the ring prevents metabolism of the compound. Degradation of
      4-chloroguaiacol was dependent on the initial ratio between the chlorinated
      compound and viable cells. Transient formation of chlorocatechols resulting from
      incubation of cells with 4-chloroguaiacol or 4,5-dichloroguaiacol was suggested
      by UV spectroscopy. Gas chromatography analyses of samples from cultures of
      strain 5ga grown on guaiacol and incubated with 4- and 4,5-dichloroguaiacol
      confirmed the presence of 4-chlorocatechol and 4,5-dichlorocatechol,
      respectively. The formation of the latter was corroborated by gas chromatography
      mass spectrometry. Thus, this strain is able to initiate metabolism of specific
      chlorinated guaiacols by O-demethylation. The starting chlorinated guaiacols and
      their O-demethylated metabolites inhibited the growth of A. junii 5ga on
      guaiacol.

PMID- 8250565
TI  - The specific growth rate of Pseudomonas putida PAW1 influences the conjugal
      transfer rate of the TOL plasmid.
AB  - The kinetics of the conjugal transfer of a TOL plasmid were investigated by using
      Pseudomonas putida PAW1 as the donor strain and P. aeruginosa PAO 1162 as the
      recipient strain. Short-term batch mating experiments were performed in a
      nonselective medium, while the evolution of the different cell types was
      determined by selective plating techniques. The experimental data were analyzed
      by using a mass action model that describes plasmid transfer kinetics. This
      method allowed analysis of the mating experiments by a single intrinsic kinetic
      parameter for conjugal plasmid transfer. Further results indicated that the
      specific growth rate of the donor strain antecedent to the mating experiment had
      a strong impact on the measured intrinsic plasmid transfer rate coefficient,
      which ranged from 1 x 10(-14) to 5 x 10(-13) ml per cell per min. Preliminary
      analysis suggested that the transfer rates of the TOL plasmid are large enough to
      maintain the TOL plasmid in a dense microbial community without selective
      pressures.

PMID- 8250566
TI  - Use of polymerase chain reaction and electroporation of Escherichia coli to
      monitor the persistence of extracellular plasmid DNA introduced into natural
      soils.
AB  - A modified protocol for DNA amplification by polymerase chain reaction (PCR)
      coupled with laser densitometric determination of the amount of PCR products,
      which allowed quantitation of target sequence numbers in soil extracts, was
      developed. The method was applied to monitor target loss during incubation of
      purified plasmid DNA in natural nonsterile soils. It revealed soil-specific
      kinetics of target loss. After 60 days, 0.2, 0.05, and 0.01% of the initially
      added nahA genes on plasmids were detectable by PCR in a loamy sand soil, a clay
      soil, and a silty clay soil, respectively. Electroporation of Escherichia coli
      was used in parallel to quantitate plasmid molecules in soil extracts by their
      transforming activity. It was found that transformation by electroporation was
      about 20 times more efficient and much less inhibited by constituents of soil
      extracts than transformation of Ca(2+)-treated cells (G. Romanowski, M.G. Lorenz,
      G. Sayler, and W. Wackernagel, Appl. Environ. Microbiol. 58:3012-3019, 1992). By
      electroporation, greater than 10,000-fold plasmid loss was monitored in
      nonsterile soils. Transforming activity was found up to 60 days after inoculation
      of the soils. The studies indicate that PCR and electroporation are sensitive
      methods for monitoring the persistence of extracellular plasmid DNA in soil. It
      is proposed that plasmid transformation by electroporation can be used for the
      monitoring in soil and other environments of genetically engineered organisms
      with recombinant plasmids. The data suggest that genetic material may persist in
      soil for weeks and even for months after its release from cells.

PMID- 8250567
TI  - Comparative in vivo efficiencies of hand-washing agents against hepatitis A virus
      (HM-175) and poliovirus type 1 (Sabin).
AB  - The abilities of 10 hygienic hand-washing agents and tap water (containing
      approximately 0.5 ppm of free chlorine) to eliminate strain HM-175 of hepatitis A
      virus (HAV) and poliovirus (PV) type 1 (Sabin) were compared by using finger pad
      and whole-hand protocols with three adult volunteers. A mixture of the two
      viruses was prepared in a 10% suspension of feces, and 10 microliters of the
      mixture was placed on each finger pad. The inoculum was allowed to dry for 20
      min, and the contaminated area was exposed to a hand-washing agent for 10 s,
      rinsed in tap water, and dried with a paper towel. In the whole-hand protocol,
      the hands were contaminated with 0.5 ml of the virus mixture, exposed for 10 s to
      a hand-washing agent, washed, and dried as described above. Tryptose phosphate
      broth was used to elute any virus remaining on the finger pads or hands. One part
      of the eluate was assayed directly for PV with FRhK-4 cells, while the other part
      was first treated with a PV-neutralizing serum and then assayed for HAV with the
      same cell line. The results are reported as mean percentages of reduction in PFU
      compared with the amount of infectious virus detectable after initial
      drying.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250568
TI  - Possible initial steps in the catabolism of 1,2-diphenylethanone (deoxybenzoin)
      by Pseudomonas fluorescens DB-5.
AB  - A natural bacterial strain, identified as Pseudomonas fluorescens DB-5, was
      isolated in enrichment cultures containing 1,2-diphenylethanone as the only
      source of carbon and energy. On the basis of characteristic features observed in
      the mass spectra of degradation intermediates, it is proposed that metabolism of
      1,2-diphenylethanone is initiated by two hydroxylations on the benzyl ring.
      Phenol, presumably arising from the benzoyl ring, was transiently detected as a
      catabolic intermediate.

PMID- 8250569
TI  - Fine regulation of cI857-controlled gene expression in continuous culture of
      recombinant Escherichia coli by temperature.
AB  - The expression at different temperatures of the lacZ gene, which is controlled by
      the lambda pL and pR tandem promoters and the cI857 temperature-sensitive
      repressor, was studied in Escherichia coli continuous cultures. At temperatures
      between 30 and 42 degrees C, beta-galactosidase activity behaved according to an
      exponential equation. By inducing a culture at a temperature within this range,
      predefined, nearly constant submaximal levels of gene expression and recombinant
      product yield can be obtained.

PMID- 8250570
TI  - Identification of the gene encoding the major cellobiohydrolase of the white rot
      fungus Phanerochaete chrysosporium.
AB  - Previous studies have shown that the cellobiohydrolases of the white rot
      basidiomycete Phanerochaete chrysosporium are encoded by a family of structurally
      related genes. In this investigation, we identified and sequenced the most highly
      transcribed gene, cbh1-4. Evidence suggests that in this fungus the dominant
      isozyme, CBH1, is encoded by chb1-4.

PMID- 8250571
TI  - Effects of glucose, growth temperature, and pH on listeriolysin O production in
      Listeria monocytogenes.
AB  - Expression of listeriolysin O of Listeria monocytogenes as a function of
      different growth conditions was studied by performing a direct hemolysin assay,
      immunoblotting experiments, and an enzyme-linked immunosorbent assay. Expression
      of listeriolysin O was reduced at a lower growth temperatures (26 degrees C) and
      at higher glucose concentrations (> or = 0.3%) in the growth media. The effect of
      glucose appeared to be due to a change in the pH of the growth media.

PMID- 8250572
TI  - Adaptation of Pseudomonas putida S12 to high concentrations of styrene and other
      organic solvents.
AB  - Pseudomonas putida S12 could adapt to grow on styrene in a two-phase styrene
      water system. Acetate was toxic for P. putida S12, but cells were similarly able
      to adapt to higher acetate concentrations. Only by using these acetate-adapted
      cells was growth observed in the presence of supersaturating concentrations of
      toxic nonmetabolizable solvents such as toluene.

PMID- 8250573
TI  - Degradation and induction specificity in actinomycetes that degrade p
      nitrophenol.
AB  - We have isolated two soil bacteria (identified as Arthrobacter aurescens TW17 and
      Nocardia sp. strain TW2) capable of degrading p-nitrophenol (PNP) and numerous
      other phenolic compounds. A. aurescens TW17 contains a large plasmid which
      correlated with the PNP degradation phenotype. Degradation of PNP by A. aurescens
      TW17 was induced by preexposure to PNP, 4-nitrocatechol, 3-methyl-4-nitrophenol,
      or m-nitrophenol, whereas PNP degradation by Nocardia sp. strain TW2 was induced
      by PNP, 4-nitrocatechol, phenol, p-cresol, or m-nitrophenol. A. aurescens TW17
      initially degraded PNP to hydroquinone and nitrite. Nocardia sp. strain TW2
      initially converted PNP to hydroquinone or 4-nitrocatechol, depending upon the
      inducing compound.

PMID- 8250574
TI  - Comparison of methods for specific depletion of ATP in Salmonella typhimurium.
AB  - Three methods of ATP depletion in Salmonella typhimurium were compared. ATP
      concentrations were lowest after arsenate treatment. Arsenate or alpha
      methylglucoside-plus-azide treatment nonspecifically lowered all nucleotide
      triphosphate levels. Histidine starvation in a hisF mutant was relatively
      specific for ATP depletion and therefore has potential in distinguishing ATP
      dependent processes from processes dependent on other nucleotides.

PMID- 8250575
TI  - Polymerase chain reaction detection of nonviable bacterial pathogens.
AB  - Polymerase chain reaction (PCR) methodologies for detection of pathogens in
      environmental samples are currently available. However, positive amplification
      products for any set of primers only signal that the appropriate target nucleic
      acid sequences were present in the sample. The presence of the amplification
      products does not imply that the target organisms were viable. Here we show that
      PCR will detect nonviable cells, as long as intact target nucleic acid sequences
      are available. In an environmental water sample, nucleic acids degraded quickly
      and were not detectable by PCR after 3 weeks even when stored at 4 degrees C.
      However, these data show that there is a window of opportunity for PCR analyses
      to result in false positives with respect to viable cells. We further show that
      care must be taken in the way samples are stored for future PCR amplifications
      and that filter sterilization of media is not acceptable for long-term
      preservation of samples for PCR.

PMID- 8250576
TI  - Chronic cutaneous lupus erythematosus treated with thalidomide.

PMID- 8250577
TI  - The molecular genetics of basement membrane diseases.
AB  - BACKGROUND: Keratin filaments, hemidesmosomes, anchoring filaments, the lamina
      densa, and anchoring fibrils each function to maintain different levels of
      basement membrane cohesion. OBSERVATIONS: Keratin 5 or 14 mutations are present
      in epidemiolysis bullosa simplex. Herlitz junctional epidermolysis bullosa is
      characterized by defects of the anchoring filament protein kalinin (alternatively
      known as nicein). Mutations of the type VII collagen gene appear to be the
      primary cause of dominant and recessive dystrophic epidermolysis bullosa. Two
      hemidesmosomal components are the bullous pemphigoid (BP) antigens: BP230 shows
      homology to desmoplakin, a desmosomal component; BP180 contains extracellular
      collagen domains. The autoantigens in cicatricial pemphigiod and IgA-mediated
      autoimmune diseases are less well understood. Type IV collagen chains are
      affected in Alport's and Goodpasture's syndromes. CONCLUSIONS: New diagnostic and
      therapeutic techniques based on these genetic/biochemical advances are currently
      being developed.

PMID- 8250578
TI  - The molecular genetics of dystrophic epidermolysis bullosa.

PMID- 8250579
TI  - Absence of human papillomavirus in squamous cell carcinomas of nongenital skin
      from immunocompromised renal transplant patients.
AB  - BACKGROUND AND DESIGN: Human papillomavirus (HPV) is accepted as a factor in the
      pathogenesis of genital squamous cell carcinomas. The incidences of both HPV
      infection and squamous cell carcinoma are increased in immunocompromised renal
      transplantation patients. The purpose of this study was to determine if HPV DNA
      is present in squamous cell carcinomas of nongenital skin in immunosuppressed
      patients. Amplification of HPV DNA was performed using the polymerase chain
      reaction. The sensitivity and specificity of the polymerase chain reaction was
      assessed on 19 positive and six negative control specimens. Twenty genital
      squamous cell carcinomas from nonimmunocompromised patients and 28 nongenital
      squamous cell carcinomas from renal transplantation patients were then analyzed.
      RESULTS: Human papillomavirus DNA was identified in 18 of 19 positive control
      specimens and zero of six negative control specimens. Human papillomavirus DNA
      was identified in four of 20 genital squamous cell carcinoma specimens. In
      comparison, no HPV DNA was identified in 28 nongenital squamous cell carcinomas
      from immunosuppressed hosts (Fisher's Exact Test, P < .025). CONCLUSIONS: These
      findings support a role for HPV in genital skin cancers and suggest that HPV does
      not play a role in the increased incidence of squamous cell carcinoma in renal
      transplantation patients.

PMID- 8250580
TI  - Rapid diagnosis of coccidioidomycosis with a DNA probe to ribosomal RNA.
AB  - BACKGROUND: Although nucleic acid probe hybridization assays were previously
      exclusively used as a tool in the research setting, such assays have recently
      become commercially available for the detection of a variety of infectious
      microorganisms. OBSERVATIONS: We used a commercially available DNA hybridization
      probe test that targets organism-specific ribosomal RNA sequences to rapidly
      diagnose a patient with disseminated coccidioidomycosis. The natural
      amplification inherent to such DNA:RNA probe systems obviates the need for
      electrophoretic separation and amplification steps, which are often required in
      more traditional DNA:DNA probe assays. With this probe, culture confirmation was
      obtained within 48 hours after the clinical specimens were received. CONCLUSION:
      Rapid DNA hybridization probe techniques have wide application in infectious
      diseases, especially those characterized by slow culture growth of pathogens such
      as deep fungi and atypical mycobacteria.

PMID- 8250581
TI  - Identification of Mycobacterium tuberculosis DNA in five different types of
      cutaneous lesions by the polymerase chain reaction.
AB  - BACKGROUND AND DESIGN: A spectrum of skin lesions are believed to be secondary to
      the presence of Mycobacterium tuberculosis. Demonstration of M tuberculosis
      directly or in culture in some of these eruptions can be difficult. We used the
      polymerase chain reaction and a primer/probe set specifically for M tuberculosis
      complex DNA to evaluate five types of skin lesions clinically considered to
      represent infection by, or reaction to, M tuberculosis. OBSERVATIONS:
      Mycobacterium tuberculosis DNA was demonstrated in paraffin-embedded sections of
      these five cases, representing a variety of clinical and histologic patterns. In
      two cases, M tuberculosis could not be demonstrated by routine cultural methods.
      CONCLUSION: DNA diagnostic methods such as the polymerase chain reaction can be
      used to rapidly identify cutaneous lesions produced by M tuberculosis.

PMID- 8250582
TI  - Multiple cutaneous ulcerations. Cutaneous ulcerations in Crohn's disease
      (metastatic Crohn's disease).

PMID- 8250583
TI  - Long-standing eczematous anogenital plaque. Langerhans' cell histiocytosis LCH
      (histiocytosis X).

PMID- 8250584
TI  - A progressive asymptomatic hyperpigmented papular eruption. Confluent and
      reticulated papillomatosis (CRP) of Gougerot and Carteaud.

PMID- 8250585
TI  - Multiple erythematous papules in both axillae. Syringomas.

PMID- 8250586
TI  - Scrofuloderma: the DNA analysis of mycobacteria by the polymerase chain reaction.

PMID- 8250587
TI  - Successful treatment of erythema induratum of bazin following rapid detection of
      mycobacterial DNA by polymerase chain reaction.

PMID- 8250588
TI  - Detection of human immunodeficiency virus type 1 and human papillomavirus type 16
      in acquired immunodeficiency syndrome-related and classic Kaposi's sarcoma.

PMID- 8250589
TI  - Effects of air pollution on children's pulmonary function in urban and suburban
      areas of Wuhan, People's Republic of China.
AB  - In May and June of 1988, the spirometric lung function of 604 children, who were
      aged 7-13 y and who were free of chronic respiratory conditions, was measured in
      the urban core and a suburb of Wuhan, China. During 1981-1988, ambient total
      suspended particulate (TSP) levels averaged 481 micrograms/m3 in the urban core
      and 167 micrograms/m3 in the suburb. In 1988, TSP levels, measured within 500 m
      of the children's homes, averaged 251 micrograms/m3 in the urban core and 110
      micrograms/m3 in the suburb. Levels of sulfur dioxide and nitrogen oxides were
      also higher in the urban core. Proportions of families who burned coal and gas
      domestically were similar in both areas. In linear and logarithmic regression
      models, height was a stronger determinant of forced vital capacity and forced
      expiratory volume in 1 s than was age or weight. In linear models, the proportion
      of variance explained by height (R-squared) ranged from 0.54 for urban females'
      forced expiratory volume in 1 s to 0.77 for suburban males and females. Both
      forced vital capacity and forced expiratory volume in 1 s were consistently lower
      in urban than suburban children. The average forced vital capacity and forced
      expiratory volume in 1 s in children 132-144 cm tall were 6.7% and 3.8% lower,
      respectively, in the urban core than the suburb; suburban-urban differences
      increased with height. Suburban-urban differences in slopes of lung function
      growth curves were statistically significant for forced vital capacity but not
      for forced expiratory volume in 1 s. Rates of clinical upper respiratory
      irritation were also generally elevated in urban children. These results strongly
      suggest that urban ambient air pollution exposure in China contributes to
      retardation in the growth of children's lung function. Confirmatory longitudinal
      studies are in progress in Wuhan and three other Chinese cities.

PMID- 8250590
TI  - Relative exposure of children to lead from dust and drinking water.
AB  - The Blackpool, Wyre and Fylde Health Authority, in the North West of England,
      could be described as a "low-level lead exposure area." Primary sources of lead
      exposure are atmospheric fallout (both indoors and outdoors) and potable water
      consumption. Deciduous teeth were collected from children living in this area as
      were water samples and outdoor dust samples. Both total lead concentrations and
      206Pb:207Pb ratios were determined for a defined subset of teeth. Significant
      differences in the total lead concentrations were found for teeth collected from
      children resident in different targeted areas (i.e., Blackpool, Fleetwood, and
      Garstang). No significant differences were found between the total lead
      concentrations or the 206Pb:207Pb ratios from dust and water samples in these
      areas. Examination of the 206Pb:207Pb ratios for dust, water, and teeth obtained
      from each area separately revealed differing patterns of exposure to lead.
      Determination of 206Pb:207Pb ratios, in addition to total lead concentrations,
      enabled the differences in sources of exposure to be identified in these
      communities. The authors conclude that isotopic analyses are an important aspect
      of community survey work, and these analyses can be helpful in accurately
      targeting intervention strategies aimed at reducing exposure to lead.

PMID- 8250591
TI  - Traffic noise and cardiovascular risk: the Speedwell study, first phase. Outdoor
      noise levels and risk factors.
AB  - As part of the Speedwell study, traffic noise exposure and risk factors for
      ischemic heart disease were studied in a sample of 2,348 men whose ages ranged
      from 45 to 63 y. The road traffic noise emission level, Leq, ranged between 51
      and 70 dB(A) (6-22 h, 10-m distance). Significant associations were found between
      noise and potential ischemic heart disease risk factors, including total
      triglycerides, platelet count, plasma viscosity, glucose (increases), and
      systolic and diastolic blood pressure (decreases). Not all results support the
      hypothesis that traffic noise increases ischemic heart disease risk. The results
      were controlled for a number of potential confounding factors.

PMID- 8250592
TI  - Traffic noise and cardiovascular risk: the Caerphilly and Speedwell studies,
      second phase. Risk estimation, prevalence, and incidence of ischemic heart
      disease.
AB  - As part of the Caerphilly and the Speedwell collaborative heart disease studies,
      associations between outdoor traffic noise level, risk factors for ischemic heart
      disease, and prevalence and incidence of ischemic heart disease were studied in
      two samples of 2,512 and 2,348 men, respectively, who were 45-63 y of age.
      Compared with the lowest noise category [Leq,6-22 h = 51-55 dB(A)], the subjects
      in the highest noise category [Leq,6-22 = 66-70 dB(A)] showed a slightly worse
      risk factor profile with respect to 9 identified endogenous risk factors.
      Logistic regression analysis suggested a marginal increase in risk (relative risk
      = 1.1) for ischemic heart disease incidence for these men based on risk factors.
      The prevalence of ischemic heart disease was slightly higher (relative risk =
      1.2) in this noise group. The observed incidence of major ischemic heart disease
      within an observation period of approximately 4 y was slightly lower (relative
      risk = 0.8) for men in the highest noise group.

PMID- 8250593
TI  - Acute leukemia and residential proximity to potential sources of environmental
      pollutants.
AB  - Possible associations between location of residence and acute leukemia risk were
      investigated in a study of 610 newly diagnosed patients, aged 18-79 y, and 618
      population controls. There was an association between ever living within 5 miles
      (8 km) of an industrial plant and leukemia risk, with adjusted odds ratios (ORs)
      of 1.4 (95% confidence interval [95% CI] = 1.0-1.9) for all acute leukemias
      combined, 1.4 (95% CI = 1.0-2.0) for acute myeloid leukemia, and 1.7 (95% CI =
      1.0-2.7) for acute lymphocytic leukemia. Odds ratios increased with decreasing
      distance from industrial sites, but a gradient with duration of residence was
      seen only among those less than age 60 who had lived within a mile of any
      industry. Suggestive associations were also observed for residence near specific
      industries, but the number of individuals living near any one industry was small.

PMID- 8250594
TI  - Umbilical cord blood lead levels in the Quebec City area.
AB  - The purposes of this study were to determine the umbilical cord blood lead levels
      in a nonindustrialized city and the effect of place of residence on the blood
      lead levels of newborns. During spring 1990, we conducted a survey of umbilical
      cord blood lead levels from 823 live newborns in two hospitals from the Quebec
      City area. The geometric mean of cord blood lead levels was 0.094 mumol/l (95%
      confidence interval [95% CI] = 0.088-0.099). Less than 1% (95% CI = 0.2-1.7) of
      the babies had cord blood lead levels at 0.48 mumol/l or greater. We estimate
      that each year in the Quebec City area between 150 and 200 newborns are at risk
      for developing psychoneurological problems during their first years of life.
      Frequency distribution of cord blood lead level did not differ significantly
      among urban, suburban, and rural areas; however, a higher proportion of cord
      blood lead levels greater than 0.25 mumol/l was observed in the urban area
      (9.4%), compared with suburban (2.6%) and rural (3.1%) areas. The proximity of
      potential environmental lead sources (highway, industry, city center) located
      within 1/2 mile (.8 km) of the mother's residence was associated with a high cord
      blood lead level. Cord blood lead levels were also elevated for newborns whose
      mothers lived in newer (< or = 5 y) and older buildings (> or = 50 y). We
      concluded that the environmental characteristics of the mother's residence are a
      better indicator of environmental lead exposure than the place of
      residence.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250595
TI  - Urinary beta 2-microglobulin concentration and mortality in a cadmium-polluted
      area.
AB  - A 9-y follow-up study of 3,178 persons who lived in a cadmium-polluted area was
      conducted to assess the influence of environmental cadmium exposure on long-term
      outcome. The standardized mortality ratios of the urinary beta 2-microglobulin
      positive subjects (> 1,000 micrograms/g creatinine) of both sexes were higher
      than those of the general Japanese population, whereas the cumulative survival
      curves were lower than those of the urinary beta 2-microglobulin-negative group.
      A significant association was also found between urinary beta 2-microglobulin and
      mortality, using a Cox's proportional hazards model. Moreover, mortality rates
      increased in proportion to increases in the amount of urinary beta 2
      microglobulin excreted. These results suggest that the prognosis for cadmium
      exposed subjects with proximal tubular dysfunction is unfavorable. The mortality
      rate tended to become higher as the severity of renal dysfunction progressed.

PMID- 8250596
TI  - The Bhopal gas disaster: it's not too late for sound epidemiology.

PMID- 8250597
TI  - The risk of malignancy with an apparently simple adnexal cyst on ultrasound.
AB  - We received data of 144 patients, who had been operated upon in the 2nd
      Department of Obstetrics and Gynecology in Vienna because of persisting
      sonographically detected "simple" adnexal cysts. Only 3 cysts were malignant (one
      of them borderline). All three patients were postmenopausal. The mean diameter of
      the malignant cysts were 7, 11 and 18 cm, respectively. 82 sonographically simple
      cysts were histologically benign. We found 27 cysts associated with chronic
      pelvic sepsis (hydrosalpinx and pseudocysts), 22 were benign cystadenomas and 10
      were endometriotic.

PMID- 8250598
TI  - Studies on transmission of hepatitis C virus from mother-to-child in the
      perinatal period.
AB  - To elucidate whether breast milk, vaginal discharge and contamination with
      maternal blood at birth are possible routes of mother-to-child transmission of
      hepatitis C virus (HCV), we examined HCV RNA in the cord and peripheral blood of
      infants, and in the blood, vaginal discharge, and breast milk of anti-HCV
      seropositive mothers. From July 1991 to July 1992, we studied 20 healthy pregnant
      women, who were seropositive with the Ortho anti-HCV EIA, and their infants.
      Using a sensitive nested polymerase chain reaction (nested PCR), we investigated
      the presence or absence of hepatitis C virus in the above-mentioned specimens.
      Moderate elevation of aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT) was observed in only one woman in the first and third
      trimesters. The nested PCR and subsequent Southern hybridization detected 0.5-5.5
      copies of HCV c-DNA. HCV RNA was detected in 17/20 blood samples (85%), 7/14
      vaginal discharge samples (50%) and 4/10 cord blood samples (40%). However, no
      HCV RNA was identified in the peripheral blood of infants or breast milk. The
      mother-to-child transmission of HCV at delivery or via breast milk does not
      appear to contribute much to maintaining the global HCV reservoir.

PMID- 8250599
TI  - Experience with the immediate treatment of iatrogenic bladder injuries and the
      repair of complex vesico-vaginal fistulae by the transvesical approach.
AB  - We describe our experience in treating 16 established cases of vesicovaginal
      fistulae in non-irradiated bladders which followed obstetric and gynecological
      procedures. The fistulae, most of which were large and complex, were successfully
      repaired surgically after two to three months intervals, using the O'Connor
      transvesical technique. The advantages of late correction using the transvesical
      approach in such cases are discussed. Thirteen additional cases of accidental
      bladder injuries during obstetric and gynecological procedures are presented.
      These injuries were successfully treated by immediate primary sutures. Our
      experience shows that bladder injuries mainly occur in women who had previously
      had a Cesarean section.

PMID- 8250600
TI  - Effects of tamoxifen on human breast cancer cells in vitro.
AB  - Long-term treatment of the estrogen sensitive human breast cancer cell line EFM
      19 with the antiestrogenic compound Tamoxifen resulted in a variant line EFM-19
      T, which was stimulated by Tamoxifen. Estrogen receptor analysis by radioligand
      assay (charcoal method), revealed a 2.5 fold higher receptor concentration in EF
      19 T cells than in the parental EFM-19 cell-line. As demonstrated with the
      immunocytochemical assay (ER-ICA) only 60% of the parental EFM-19 cells were
      estrogen receptor positive, whereas 98% of the EFM-19 T cells expressed estrogen
      receptor protein. In addition, receptor content per cell was higher in the
      Tamoxifen treated subline than in the parental cell line. Analogous with the
      growth promoting effect of Tamoxifen on EFM-19 T cells, Tamoxifen acted like
      estrogen leading to a down regulation of cellular estrogen receptor
      concentration. The partial growth dependency of the EFM-19 T cells on the
      presence of Tamoxifen demonstrates estrogenic effects of Tamoxifen and explains
      the withdrawal response obtained in the treatment of breast cancer patients when
      remission occurs after termination of ineffective treatment with Tamoxifen.

PMID- 8250601
TI  - The "forgotten" intrauterine device: a cause of infertility.
AB  - We present a case of infertility due to a "forgotten" IUD. Users of intrauterine
      devices are reported to have an increased risk of frank or subclinical genital
      infections which later may be the cause of infertility. Other mechanisms of
      causing infertility are possible. During the last two years we have seen three
      infertile patients with an IUD in situ. Two had ovulation, and one got pregnant
      immediately after the IUD was removed.

PMID- 8250602
TI  - Polymyositis and vaginal carcinoma.
AB  - The strange association of Dermatomyositis-Polymyositis (DM-PM) and cancer has
      been known for many years. We present the case of a 57-year-old woman with
      polymyositis refractory to steroid therapy, in whom extensive investigation
      finally revealed a squamous cell carcinoma of the vagina. The clinical course of
      myositis paralleled the course of vaginal cancer, with complete resolution of
      symptoms after radiotherapy for the malignancy.

PMID- 8250603
TI  - Vaginosonographically guided paracentesis in a woman with severe
      thrombocytopenia.
AB  - Coagulation disorders and obesity might complicate transabdominal paracentesis.
      In a woman with severe thrombocytopenia we used the vaginal approach guided by
      vaginosonography to obtain ascitic fluid for analysis.

PMID- 8250604
TI  - Concurrent ovarian serous carcinoma and osteogenesis imperfecta.
AB  - Because epithelial malignancies in patients with osteogenesis imperfecta are
      rare, it has been postulated that these patients may have "cancer-protection". A
      case of stage III b ovarian serous carcinoma in a woman with congenital
      osteogenesis imperfecta is now presented and discussed.

PMID- 8250605
TI  - Late miscarriage and intraamniotic candidiasis in a woman with a retained
      intrauterine contraceptive device.

PMID- 8250606
TI  - Blocking cartilage destruction with metalloproteinase inhibitors: a valid
      therapeutic target?

PMID- 8250607
TI  - Extra-articular manifestations of rheumatoid arthritis: risk factors for serious
      gastrointestinal events.
AB  - OBJECTIVES: Serious upper gastrointestinal events are an important threat to
      patients with arthritis who are treated with non-steroidal anti-inflammatory
      drugs (NSAIDs). In this study risk factors for serious upper gastrointestinal
      events are identified in patients with possible or definite rheumatoid arthritis
      (RA). METHODS: A retrospective analysis of factors that might contribute to the
      risk of serious upper gastrointestinal events was performed in a cohort of 2315
      consecutive patients with possible or definite RA. The relative influences of
      disease severity, drug treatment, particularly with corticosteroids, and history
      of peptic ulceration were analysed with a conditional logistic regression model
      for the 106 patients with serious upper gastrointestinal intestinal events and
      for an equal number of control patients who were matched for age, gender, number
      of criteria for RA, and disease duration. RESULTS: The incidence rate for serious
      upper gastrointestinal events was 4.0/1000 patients in each year. The study
      reconfirmed that age over 60 years, history of peptic ulceration, and use of
      corticosteroids are risk factors. The presence of extra-articular manifestations
      of RA was associated with a two to 11-fold increase in the risk for serious upper
      gastrointestinal events. This risk was independent of the use of corticosteroids.
      CONCLUSION: Disease severity, in particular the presence of extra-articular
      features, may be an important factor in the pathogenesis of upper
      gastrointestinal ulceration in patients with RA who are treated with NSAIDs.

PMID- 8250608
TI  - Bronchiectasis and rheumatoid arthritis: a clinical study.
AB  - OBJECTIVES: To examine the relation between rheumatoid arthritis (RA) and
      bronchiectasis (BR). METHODS: Disease activity, outcome, extra-articular
      manifestations, and laboratory features were compared in 32 patients with BR and
      RA (RA-BR group), 32 matched patients with RA without BR (RA group), and 31
      patients with BR but without arthritis (BR group). RESULTS: In 30 of the 32 (94%)
      patients with RA-BR, BR preceded RA. There was no functional or radiological
      difference between the RA-BR and RA groups, and except for xerophthalmia, which
      was more common in patients with RA-BR than patients with RA, there was no
      difference in extra-articular or laboratory features. CONCLUSIONS: Bronchiectasis
      does not lead to a more aggressive disease course in RA and, despite the
      recognised association, BR is not an extra-articular manifestation of rheumatoid
      disease.

PMID- 8250609
TI  - Identification of a subset of patients with scleroderma with severe pulmonary and
      vascular disease by the presence of autoantibodies to centromere and histone.
AB  - OBJECTIVES: The role of autoantibodies in the investigation and management of
      rheumatic diseases is well recognised. The objective of this study was to
      determine the clinical significance of the co-occurrence of antibodies to
      centromere and histone in serum samples from patients investigated for systemic
      rheumatic diseases. METHODS: Serum samples from 1316 consecutive patients were
      screened for antinuclear antibodies and the clinical findings in patients with
      antibodies to centromere alone were compared with those with antibodies to both
      centromere and histone. RESULTS: Twenty six patients had antibodies to
      centromere. Fourteen patients had antibodies to centromere alone and 12 patients
      had antibodies to centromere and histone. Four of the 12 patients with antibodies
      to centromere and histone had diffuse scleroderma with severe pulmonary or
      vascular disease. CONCLUSIONS: A subset of patients with scleroderma with
      antibodies to centromere and histone has been identified retrospectively, who
      have severe pulmonary or vascular disease. It will be of interest to follow up
      the clinical course of other patients with scleroderma who have both antibodies
      for the development of pulmonary or vascular disease.

PMID- 8250610
TI  - Definition of osteoarthritis of the knee for epidemiological studies.
AB  - OBJECTIVES: There are no agreed criteria for osteoarthritis (OA) of the knee in
      population studies. The radiographic scoring system of Kellgren and Lawrence has
      been the system most used in the past and although other methods have been
      developed, comparisons have not been performed. Therefore these grading systems
      were compared in radiographs from a general population sample. METHODS:
      Anteroposterior weightbearing radiographs of 1954 knees from 977 women aged 45-64
      years from the Chingford population study were read by a variety of methods,
      including quantitative measures of minimum joint space, qualitative measures of
      osteophytes and of joint space, and a qualitative Kellgren and Lawrence global
      score. All qualitative methods used standardised atlases. Intra-observer and
      interobserver reproducibility was tested on a subgroup of 100 films using three
      observers and two readings. Variables were dichotomised at the tenth and second
      centiles to define OA. Odds ratios were calculated for each method for the
      association of OA with knee pain, obesity, and with each of the other methods.
      RESULTS: Most methods had high intraobserver and interobserver reproducibility,
      except for measurements of lateral joint space. The best predictors of knee pain
      were the presence of osteophytes and the Kellgren and Lawrence grade. Methods
      measuring narrowing performed less well, with measurements of lateral joint space
      being particularly poor. Similar results were achieved in the comparison with
      obesity and in the comparisons between methods. CONCLUSIONS: These data suggest
      that the presence or absence of a definite osteophyte read by a single observer
      with an atlas is the best method of defining OA of the knee for epidemiological
      studies in women. Assessment of narrowing may be better used in evaluating
      severity.

PMID- 8250611
TI  - Complement activating properties of monoreactive and polyreactive IgM rheumatoid
      factors.
AB  - OBJECTIVES: To estimate the complement activating properties of monoclonal,
      monoreactive, and polyreactive IgM rheumatoid factors derived from Epstein-Barr
      virus transformed B cells isolated from peripheral blood and synovial tissue of
      patients with rheumatoid arthritis (RA). METHODS: An enzyme linked immunosorbent
      assay (ELISA) was used to measure the activation of the classical pathway of
      complement by monoclonal IgM rheumatoid factor. Monoclonal IgM rheumatoid factor
      was bound to IgG Fc adsorbed onto microtitre plates and then reacted with diluted
      normal human serum as a source of complement. The activation and binding of C4
      were measured with F(ab')2 antibody to human C4. The complement activating
      property of IgM rheumatoid factor bound to IgG Fc was tentatively expressed as
      the ratio of the amount of bound C4 to the amount of bound IgM rheumatoid factor.
      RESULTS: The complement activating property of monoreactive IgM rheumatoid factor
      was shown to be about three times higher than that of polyreactive IgM rheumatoid
      factor. CONCLUSIONS: Monoreactive IgM rheumatoid factor with the higher
      complement activating property would result in a greater degree of complement
      dependent inflammation and might have a more important pathogenic role in RA than
      polyreactive IgM rheumatoid factor.

PMID- 8250612
TI  - Correlation of the size of type II transforming growth factor beta (TGF-beta)
      receptor with TGF-beta responses of isolated bovine articular chondrocytes.
AB  - OBJECTIVES: Transforming growth factor beta (TGF-beta) is a multipotent regulator
      of cell proliferation and extracellular matrix production. The effect of TGF-beta
      on chondrocyte matrix production was studied in relation to the expression of TGF
      beta binding proteins. The effect of TGF-beta on proteoglycan synthesis of
      isolated articular chondrocytes depended on the culture period. Proteoglycan
      synthesis of chondrocytes which were cultured for one day was inhibited by TGF
      beta whereas proteoglycan synthesis of chondrocytes cultured in monolayer for
      seven days or longer was stimulated by TGF-beta. To investigate if this
      differential response is related to a distinct expression of TGF-beta receptors,
      this parameter was studied by affinity labelling. METHODS: Chondrocytes were
      incubated with 100 pM TGF-beta labelled with iodine-125. Crosslinking was
      performed using 0.25 mM disuccinimidyl suberate. Membrane proteins were extracted
      and analysed by denaturating sodium dodecylsulphate polyacrylamide gel
      electrophoresis (SDS-PAGE) and autoradiography. RESULTS: Freshly isolated and
      cultured chondrocytes expressed types I, II, and III TGF-beta receptors. The type
      II TGF-beta receptor of cultured chondrocytes appeared to be about 15 kilodaltons
      smaller than the type II TGF-beta receptor expressed on freshly isolated
      chondrocytes, however. CONCLUSIONS: As the type II TGF-beta receptors appears to
      be involved in signal transduction, this change in size of the type II TGF-beta
      receptor might be related to the differential effect of TGF-beta on proteoglycan
      synthesis of freshly isolated and cultured bovine articular chondrocytes.

PMID- 8250613
TI  - Effects of the molecular weight of hyaluronic acid and its action mechanisms on
      experimental joint pain in rats.
AB  - OBJECTIVES: It has been shown previously that hyaluronic acid (HA) has an
      analgesic action on bradykinin induced pain in the knee joints of rats. This
      study further clarifies the effects of the molecular weight of HA and its
      mechanism of action in the same model using HA of molecular weight 800 to 2.3 x
      10(6) daltons and a bradykinin antagonist. METHODS: Bradykinin and the test HA
      preparations were given to rats by intra-articular injection, and the severity of
      pain was evaluated by a change in the walking behaviour. RESULTS: HA with a
      molecular weight greater than 40 kilodaltons produces analgesic effects with a
      simultaneous or earlier injection. The ID50 values of HA with molecular weight
      40, 310, 860, and 2300 kilodaltons were greater than 2.5, 0.6, 0.07, and 0.06
      mg/joint respectively. The duration of the analgesic effect of 860 and 2300
      kilodalton HA was 72 hours at 10 mg/ml, whereas that of 310 kilodalton HA was
      short, being undetectable after 24 hours. The analgesic action of HA of 860
      kilodaltons was not changed by pretreatment with four saccharide HA and inhibited
      by pretreatment with HA larger than six to eight saccharides, capable of binding
      to HA receptors. Further, HA did not interfere with the analgesic action of the
      bradykinin antagonist, indicating that HA does not directly bind with bradykinin
      receptors. CONCLUSIONS: HA with a molecular weight of greater than 40 kilodaltons
      produced an analgesic effect, and HA of 860 and 2300 kilodaltons produced high
      and long-lasting analgesia. These effects of HA appear to be caused by the
      interaction between HA and HA receptors.

PMID- 8250614
TI  - Comparative study of the skin pathergy test with blunt and sharp needles in
      Behcet's disease: confirmed specificity but decreased sensitivity with sharp
      needles.
AB  - OBJECTIVE: To compare the specificity and sensitivity of the skin pathergy test
      performed with blunt and sharp needles in patients with Behcet's disease.
      METHODS: The skin pathergy test was performed using the simultaneous four needle
      prick method with blunt and sharp, thick and thin needles in 92 patients with
      Behcet's disease, 64 healthy controls, and 128 patients without Behcet's disease.
      The test was evaluated at 48 hours. RESULTS: No positive skin pathergy test was
      found in healthy controls and patients without Behcet's disease. The frequency
      and intensity of the positive skin pathergy test with blunt needles were
      significantly higher than those with sharp needles. CONCLUSION: This study
      reconfirmed the specificity of a positive skin pathergy test for Behcet's disease
      using blunt and sharp needles and showed a decreased sensitivity and intensity of
      the reaction with sharp needles.

PMID- 8250615
TI  - Therapeutic value of colchicine in the treatment of patients with psoriatic
      arthritis.
AB  - OBJECTIVE: To test the hypothesis that colchicine is an effective treatment of
      psoriatic arthritis. METHODS: Twenty five patients with psoriatic arthritis were
      entered into a two centre, double blind, crossover study of 23 weeks' duration
      comparing the therapeutic effect of colchicine (0.6-1.8 mg/day) with placebo.
      RESULTS: No significant difference was noted between colchicine or placebo
      treatment for the primary outcome measure (Lansbury joint count) or any of the
      seven secondary outcome measures. No change in the psoriasis was noted during
      active or placebo treatment. Adverse clinical effects were reported more often
      during treatment with colchicine (14 patients) than with the placebo (four
      patients), resulting in the early withdrawal of three patients receiving
      colchicine from the trial. Increased creatine kinase values, without weakness,
      occurred during treatment with colchicine (five patients) and placebo (four
      patients). CONCLUSIONS: In conclusion, our study did not provide evidence that
      colchicine is of therapeutic value in the treatment of psoriatic arthritis.

PMID- 8250616
TI  - Current issues in arthrogenous inhibition.
AB  - Joint disease commonly results in severe weakness of associated muscles. Efforts
      to restore strength are often unsuccessful, even in the absence of pain. This is
      because of the underlying inhibition of motoneurones by afferent signals from in
      and around the affected joint, 'arthrogenous inhibition'. This phenomenon has
      received scant scientific attention, but several experimental techniques are now
      available with which it can be studied in man. Animal studies suggest possible
      neurophysiological mechanisms. Selective atrophy of different muscle fibre types,
      perhaps implying selective inhibition of different types of motor unit, remains
      unexplained, however. The severity of arthrogenous inhibition can be temporarily
      reduced by silencing afferent traffic but none of the techniques is yet generally
      applicable in practice. An alternative therapeutic approach is to produce
      involuntary muscle contractions by electrical stimulation. The effectiveness of
      therapeutic electrical stimulation may depend on the frequency and other
      characteristics of the stimulus.

PMID- 8250617
TI  - Acquired Brown's syndrome.

PMID- 8250618
TI  - Effect of hormone replacement therapy on markers of bone metabolism in RA.

PMID- 8250619
TI  - Fibromyalgia in the workplace.

PMID- 8250620
TI  - Large vessel disease in CREST.

PMID- 8250621
TI  - Simultaneous onset of giant cell arteritis and subacute thyroiditis.

PMID- 8250622
TI  - Compartment syndrome, stiff joints, and diabetic cheiroarthropathy.

PMID- 8250623
TI  - An historical review of malaria, kala-azar and filariasis in Bangladesh in
      relation to the Flood Action Plan.
AB  - This paper reviews the evidence of a link between flood control and vector-borne
      disease in Bengal/Bangladesh. Malaria is historically associated with reduced
      flooding and embankment construction in the flood plains of Bengal. The land west
      and south of the Jamuna river was highly malarious in 1916 but is not so today.
      The lands east of the Jamuna now have a higher, though still small, risk. The
      reduction in health risk can be attributed to the intensification of land use and
      human population density. Although there are many mosquito species, the abundance
      of the former malaria vector appears to have declined as environmental change
      removed its breeding sites. Visceral leishmaniasis (kala-azar) is a serious
      disease which is fatal if left untreated. It occurs in irregular, periodic
      epidemics and is currently increasing in Bangladesh. In the past, malaria and
      kala-azar were confused and the prevalence of both may have been increased by
      embankment programmes. Both diseases are unstable and there is insufficient
      historical information to predict, with certainty, the consequences of
      environmental change. Reduced flooding accompanied by increased pollution will
      probably control the malaria vector. More information is needed about the
      response of the kala-azar vector to flooding. Bancroftian filariasis is non-fatal
      but causes chronic morbidity. It has had a widespread but usually low prevalence
      in Bangladesh, with both rural and urban foci. There are few recent data.
      Increasing organic pollution and drainage obstruction are expected to favour the
      vector and increase transmission.

PMID- 8250624
TI  - Molecular karyotype variation in Leishmania (Viannia) peruviana: indication of
      geographical populations in Peru distributed along a north-south cline.
AB  - Forty-one Leishmania peruviana isolates were selected along a north-south
      transect which crossed areas endemic for uta in three different biogeographical
      regions in the Peruvian Andes. The isolates were analysed by molecular
      karyotyping and hybridization with three chromosome-derived DNA probes. All the
      isolates could be distinguished from L. braziliensis by their pLb-134
      hybridization patterns. However, the patterns with the other probes (pLb-168 and 
      22) could be used to cluster the Peruvian isolates in discrete groups
      (karyodemes) which varied in their level of similarity with L. braziliensis. The
      geographical distribution of these karyodemes supports the hypothesis that eco
      graphical isolation has contributed to the heterogeneity of L. peruviana.

PMID- 8250625
TI  - Cutaneous leishmaniasis due to Leishmania aethiopica, on Mount Elgon, Kenya.
AB  - A survey of cutaneous leishmaniasis was carried out on the slopes of Mount Elgon,
      Kenya, including a detailed study of two villages in which cases were known to
      occur. The disease appeared to be restricted to altitudes between 1750 and 1900
      metres, which coincides with an escarpment region. Vector sandflies were not
      found in houses and transmission appeared to be predominantly associated with
      caves found in the escarpment region. The parasites which were isolated were
      identified as Leishmania aethiopica.

PMID- 8250626
TI  - Ultrastructural observations on caecal epithelial cells invaded by first
      generation merozoites of Eimeria tenella in vivo.
AB  - Transmission electron microscopy was used to study the effects of invasion of
      caecal epithelial cells by first-generation merozoites of Eimeria tenella. At 53
      h post-infection, merozoites were found within mature meronts and in enterocytes
      of the crypt epithelium. Following merozoite invasion, the terminal web of
      microfilaments of the invaded cell was disrupted and cell extensions were present
      on the enterocyte surface. There was a marked morphological alteration of the
      host cell resulting in loss of microvilli and extensive bulging of cytoplasm into
      the crypt lumen. Multiple invasion of enterocytes and invasion of goblet cells
      were observed. Large numbers of mast cells infiltrated the mucosa, identified by
      the metachromatic staining of their granules, and were found within the lamina
      propria, epithelium and lumen. Merozoites were found within mast cells and
      lymphocytes within the lumen.

PMID- 8250627
TI  - Schistosomiasis around Siavonga, on the shores of Lake Kariba, Zambia.
AB  - A schistosomiasis prevalence survey was carried out at Lake Kariba, Zambia--only
      the second since the creation of the lake more than 30 years ago. In the 20 or so
      years since the first study the prevalence of Schistosoma mansoni has increased
      from 16% to 56% while that of S. haematobium has dropped from 69% to 17%. There
      was variability in the infectivity of contact sites (P < 0.001) and this had an
      impact on prevalence. In contrast, sex, age (within the range 5-19 years),
      residential area (distance from the lakeshore) and activity at the contact site
      had no significant effect on prevalence (P > 0.05). The population at Matinangala
      was more at risk of infection by both S. haematobium (P < 0.001) and S. mansoni
      (P < 0.05) than the Siavonga population. Both Biomphalaria pfeifferi and Bulinus
      globosus were present in the area and factors which may be influencing their
      distribution are discussed.

PMID- 8250628
TI  - Plasmid encoded multi-drug resistance in Salmonella typhi from Pakistan.
AB  - Twenty-five isolates of Salmonella typhi made from cases of typhoid fever during
      1990-1991 in Rawalpindi and Islamabad, were examined. All isolates were resistant
      to chloramphenicol, ampicillin, tetracycline, streptomycin, sulphamethoxazole and
      trimethoprim, but were sensitive to nalidixic acid, ofloxacin, ciprofloxacin,
      cefuroxime and cefotaxime. A single large 98 MDa plasmid was identified in all
      the isolates. The plasmid was self-transferable and encoded resistance to
      chloramphenicol, ampicillin, tetracycline, streptomycin, sulphamethoxazole and
      trimethoprim. Restriction endonuclease analysis patterns after EcoRI and HindIII
      digestion of the 98 MDa multi-drug resistance plasmids from each of the S. typhi
      isolates and transconjugants were the same.

PMID- 8250629
TI  - Plasmodium falciparum sporozoite and entomological inoculation rates at the Ahero
      rice irrigation scheme and the Miwani sugar-belt in western Kenya.
AB  - Anopheles arabiensis and An. funestus were collected by pyrethrum spray sheet
      collections in houses and by human-bait catches at a village in western Kenya
      adjacent to the Ahero rice irrigation scheme; and using the same methods, An.
      gambiae s.l. and An. funestus were collected at Miwani, a village in the sugar
      cane belt. Plasmodium falciparum sporozoite rates were determined by ELISA. At
      Ahero the mean sporozoite rates were 1.1% and 4.3% in An. arabiensis and An.
      funestus, respectively, while at Miwani the rates were 6.0% in An. gambiae s.l.
      and 4.3% in An. funestus. Entomolgoical inoculation rates (EIR) were derived from
      both human-bait collections (IR-HBC) and by the proportion of human blood-fed
      females caught resting indoors (IR-HBF). The IR-HBF appeared to be a more
      realistic index of EIR. At Ahero and Miwani people were exposed to an average of
      416 and 91 infective bites/person/year, respectively. The main vectors were An.
      funestus at Ahero and An. gambiae s.l. at Miwani. In view of the intense and
      perennial malaria transmission at Ahero, vector control by insecticides should be
      considered, while at Miwani, where transmission is seasonal, permethrin
      impregnated bed nets could be an alternative to indoor spraying. These measures
      must be augmented with availability of effective antimalarials.

PMID- 8250630
TI  - Correlation between the preferred biting site of Culex quinquefasciatus and the
      region of the body affected by clinical filariasis.
AB  - Entomological and filariasis surveys were conducted simultaneously in a rural and
      an urban environment in West Bengal from September 1986 to August 1987. The aim
      of the surveys was to see if any correlation existed between the preferred biting
      site of Culex quinquefasciatus, the filarial vector, and the region of the body
      affected by clinical filariasis. Significantly more mosquitoes (> 55%) attacked
      the thighs, legs and feet of human volunteers than other sites on their bodies,
      whether the volunteers were indoors or outdoors, in rural or urban environments.
      Significantly more patients had clinical filariasis of these lower body parts
      than of the upper parts. The vector's preferred biting sites and the anatomical
      sites most affected by clinical filariasis were therefore the same.

PMID- 8250631
TI  - Comparison of three strategies for mass distribution of ivermectin in Achi,
      Nigeria.
AB  - The Nigerian Ministry of Health has estimated that there are 40 million people in
      Nigeria at risk of onchocerciasis, and has asked for supplies of free ivermectin
      (Mectizan) to be donated by Merck, Sharpe and Dohme. In anticipation, three
      methods of distribution--door-to-door, clinic-based and centralized--were
      compared for cost-effectiveness. Costs were based on market values, and included
      salaries of and per diem payments to staff, cost of transportation, and
      subsistence during field activities. Effectiveness was measured by the total
      number of subjects successfully dosed. The local cost of dosing was N3.7 per
      person for the centralized system, N5.8 for the clinic-based system, and N9.2 for
      the door-to-door system (N10 = U.S. $1).

PMID- 8250632
TI  - Acanthamoeba infection of peptic ulcer.

PMID- 8250633
TI  - Toxoplasmosis in goats: a sero-epidemiological study in Peninsular Malaysia.

PMID- 8250634
TI  - Infectivity of the newly-isolated Han-pao strain of Schistosoma japonicum from
      Taiwan to some oncomelanid snails.

PMID- 8250635
TI  - Echinostomiasis in the highlands of Irian Jaya, Indonesia.

PMID- 8250636
TI  - High prevalence and intensity of hookworm infection in the Dhofar Governorate,
      Oman.

PMID- 8250637
TI  - Haemoglobin and blood group (ABO and rhesus) phenotypes in tuberculosis patients
      of the Sudan savanna of Nigeria.

PMID- 8250638
TI  - Coral snake bite and severe local pain.

PMID- 8250639
TI  - Novel, delta-opioid receptor-selective peptide antagonists: demonstration of a
      possible opioid interaction in the absence of a protonated nitrogen and attempts
      to locate the protonated nitrogen site.
AB  - We have recently (Ronai et al., 1992) introduced a family of novel delta-opioid
      receptor-selective peptide antagonists, based on the Tyr-Pro-Gly-Phe-Leu-Thr
      structure, where the nitrogen accepts substituents that make protonation possible
      (e.g. diallyl) as well as substituents (e.g. t-Boc) where protonation cannot
      occur. In this paper, we present the details of a design strategy where the
      structurally closely related biologically active and inactive compounds are
      suggestive of conformational requirements of action. Furthermore, since even
      those derivatives of the antagonist peptides where the N-terminus was free were
      either devoid of opioid agonist activity or were extremely weak agonists, it is
      suggested that these antagonists do not interact with the conventional "opioid
      nitrogen site". To find this "conventional" site, a number of N-substituted
      (phenylglycyl-, alpha-Boc-lysyl-, alpha-Phe-beta-alanyl-) derivatives of Tyr-Pro
      Gly-Phe-Leu-Thr hexapeptide were synthesized and their biological activities were
      determined in the mouse vas deferens bioassay.

PMID- 8250640
TI  - No development of tolerance to the hypotensive effect of KRN2391, a novel
      vasodilator containing a nitrate moiety.
AB  - The present studies were performed to examine whether tolerance develops to the
      hypotensive effects of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3
      pyridinecarboximidamide monomethanesulfonate. Rats were administered KRN2391 (0.3
      or 1 mg/kg, s.c.) or nitroglycerin (10 mg/kg, s.c.) three times a day for 1 to 8
      days and blood pressure was then measured under anesthesia. Chronic pretreatment
      with nitroglycerin attenuated the decrease in blood pressure induced by i.v.
      nitroglycerin but not that by i.v. KRN2391. Chronic pretreatment with KRN2391
      (0.3 or 1 mg/kg, s.c.) had no effect on the decreases in blood pressure induced
      by i.v. nitroglycerin or i.v. KRN2391. It can be concluded that, in this rat
      model, no tolerance develops to the hypotensive effects of KRN2391.

PMID- 8250641
TI  - Protective action of methyldopa against ouabain-induced cardiac arrhythmias and
      lethality.
AB  - Methyldopa (25, 50 and 100 mg/kg, i.p.) was studied for its effect on cardiac
      arrhythmias and lethality induced by slow intravenous infusion of ouabain in
      guinea-pigs. Methyldopa increased the dose of ouabain required to elicit the
      arrhythmic stages and lethality. However, it did not provide any protection in
      reserpinized guinea-pigs. Methyldopa also inhibited the rate of the ouabain
      induced rise in blood pressure and the peak pressor response. Yohimbine
      significantly antagonized the protective action of methyldopa. It is concluded
      that the protective action of methyldopa against the arrhythmogenic and lethal
      effects of ouabain may be due to its action on the indirect neural components of
      ouabain toxicity, mediated through stimulation of alpha 2-adrenoceptors.

PMID- 8250642
TI  - The novel thromboxane A2 receptor antagonist KW-3635 reduces infarct size in a
      canine model of coronary occlusion and reperfusion.
AB  - The effect of KW-3635, a novel thromboxane A2 receptor antagonist, on infarct
      size was examined in anesthetized dogs subjected to 1.5 hr of occlusion of the
      left anterior descending coronary artery followed by 4.5 hr of reperfusion. KW
      3635 (1 mg/kg, i.v.) was administered 1 hr before reperfusion and continuously
      infused (1 mg/kg/hr, i.v.) throughout the experiment. KW-3635 significantly (p <
      0.001) reduced the infarct size (30.5% in the KW-3635-treated group as compared
      with 58.7% in the vehicle-treated group). KW-3635 almost completely inhibited
      platelet aggregation (ex vivo) induced by epinephrine (10 microM) + U-46619 (1
      microM). KW-3635 attenuated the loss of creatine phosphokinase activity from the
      ischemic myocardium. Histopathological examination revealed that KW-3635
      prevented neutrophil accumulation into the ischemic myocardium, ameliorated
      eosinophilic changes and inhibited contraction band formation in the ischemic
      myocardium. These results indicate that KW-3635 has a cardioprotective activity
      and suggest that the inhibition of activation or accumulation of neutrophils is
      involved in the cardioprotection following thromboxane A2 receptor blockade.

PMID- 8250643
TI  - Effects of catecholamine uptake inhibitors on the positive inotropic responses to
      isoprenaline, dobutamine and dopexamine in human, rat and guinea-pig atrial heart
      muscle.
AB  - The inotropic effects of isoprenaline, dobutamine and dopexamine were studied in
      human right atrial myocardium and in rat and guinea-pig left atria electrically
      stimulated at 1 Hz. To investigate the contribution of endogenously released
      catecholamines to the positive inotropic effects of beta-adrenoceptor agonists,
      experiments were performed both in the absence and in the presence of the uptake
      inhibitors desipramine and corticosterone. In all three species, the maximum
      positive inotropic responses to isoprenaline and dobutamine were not influenced
      by the pretreatment, whereas the responses to dopexamine were modified, i.e. the
      maximum force increase was reduced and the concentration-response curves were
      shifted to the right. After uptake inhibition, the decrease in positive inotropic
      action of dopexamine was largest in rat atria followed by guinea-pig and human
      atria. It is concluded that, in the untreated atrial muscle from all three
      species, endogenous catecholamines contribute only to the inotropic responses of
      dopexamine but not to those of isoprenaline or dobutamine.

PMID- 8250644
TI  - Guanidino succinic acid is not the endogenous source of endothelium-derived
      relaxing factor in the porcine isolated splenic artery.
AB  - The possibility that guanidino succinic acid is the major endogenous source of
      endothelium-derived relaxing factor has been examined using the porcine isolated
      splenic artery. Administration of 100 microM NG-nitro-L-arginine methyl ester (L
      NAME) caused a substantial, endothelium-dependent contraction of the splenic
      artery that was inhibited by L-arginine (1 mM) but was unaffected by D-arginine
      (1 mM). L-NAME enhanced the responsiveness of the splenic artery to 5
      hydroxytryptamine in endothelium-intact segments only, and the potentiating
      action of L-NAME was inhibited by L-arginine but not by D-arginine.
      Administration of 100 microM guanidino succinic acid did not relax the splenic
      artery and it did not inhibit or reverse contractions of the splenic artery
      induced by L-NAME. Administration of guanidino succinic acid, either before or
      after L-NAME, did not affect the potentiating action of L-NAME on the 5
      hydroxytryptamine-induced contraction of the splenic artery in endothelium-intact
      segments. Although substance P caused an endothelium-dependent relaxation of
      preconstricted segments of the splenic artery, guanidino succinic acid did not
      relax preconstricted, endothelium-intact or endothelium-denuded segments of the
      artery. L-NAME inhibited the relaxation induced by substance P in endothelium
      intact preparations. The findings for the effects of arginine are consistent with
      L-arginine being a source of endothelium-derived relaxing factor in the porcine
      splenic artery, while observations with guanidino succinic acid indicate that it
      is not a substrate for the synthesis of endothelium-derived relaxing factor in
      this blood vessel.

PMID- 8250645
TI  - Effects of the acetylcholinesterase inhibitor ENA-713 on ischemia-induced changes
      in acetylcholine and aromatic amine levels in the gerbil brain.
AB  - The effects of a new acetylcholinesterase inhibitor, ENA-713, on ischemia-induced
      changes in acetylcholine, monoamines, and their metabolites, were studied in the
      gerbil. ENA-713 (0.2 mg/kg) or saline was administered intraperitoneally to
      gerbils 30 min before induction of cerebral ischemia by bilateral carotid
      occlusion. Pretreatment with ENA-713 mitigated the ischemia-induced abnormalities
      of the cholinergic, dopaminergic and serotoninergic systems in the gerbil brain,
      although it had virtually no effect on acetylcholine, monoamines, or their
      metabolites in any region of the normal gerbil brain. These findings suggest that
      ENA-713 has beneficial effects against ischemia-induced cerebral disorders. Thus,
      ENA-713 seems to be promising as a preventive or therapeutic agent for
      cerebrovascular dementia due to cerebral ischemia and might be useful for the
      treatment of Alzheimer-type dementia which is associated with multiple
      neurotransmitter abnormalities in the brain.

PMID- 8250646
TI  - Effect of (+-)-propranolol and clonidine on stress- and chemically induced
      gastric ulcers in rats.
AB  - The influence of (+-)-propranolol and clonidine on stress- and various chemically
      induced gastric ulcers in rats, together with their influence on various
      biochemical parameters which affect the development of the induced ulcers, was
      examined. Pretreatment of rats with (+-)-propranolol (10-100 mg/kg) and with
      clonidine (0.03-0.3 mg/kg) given orally, significantly reduced indomethacin- (30
      mg/kg, orally) and reserpine- (5 mg/kg, i.p.) induced ulcers. In addition,
      propranolol pretreatment significantly reduced ethanol- and cold-stress-induced
      ulcers, whereas pretreatment with orally given clonidine significantly enhanced
      these ulcers. Pretreatment with propranolol significantly increased gastric mucus
      synthesis and the nonprotein sulfhydryl content and reduced gastric lipid
      peroxidation without affecting gastric acid secretion. Pretreatment of the
      animals with clonidine significantly increased gastric mucus secretion and
      decreased total gastric acidity. It did not affect the gastric nonprotein
      sulfhydryl content and lipid peroxidation. The drug-induced effects on the
      experimentally induced ulcers may be related to their induced biochemical
      alteration in the gastric parameters measured.

PMID- 8250647
TI  - Adherence to treatment and health outcomes.
AB  - Adherence (or compliance) is the extent to which a person's behavior coincides
      with medical or health advice. Recent evidence indicates that patients who adhere
      to treatment, even when that treatment is a placebo, have better health outcomes
      than poorly adherent patients. Based on this evidence, we now believe that the
      outcomes of treatment are not solely attributable to the specific action of a
      drug, but may also depend on other nonspecific therapeutic effects. We consider
      the implications of these findings for the design and interpretation of clinical
      research as well as for the care of patients.

PMID- 8250648
TI  - Recall of recommendations and adherence to advice among patients with chronic
      medical conditions.
AB  - BACKGROUND: Patient adherence to treatment regimens may be a critical mediator
      between physician recommendations and patient outcomes, but levels of adherence
      have not been compared across disease groups, and patient self-reports have not
      been well validated. METHODS: To determine recall of and adherence to physicians'
      recommendations among patients with chronic medical conditions and to measure the
      correspondence between self-reported adherence and disease activity, we analyzed
      data from the Medical Outcomes Study. A total of 1751 patients with diabetes
      mellitus, hypertension, and heart disease were identified among 20,223 patients
      visiting family physicians, general internists, cardiologists, and
      endocrinologists in 1986. Main outcome measures included recall of 15 disease
      specific recommendations, self-reported general and specific adherence, and
      correlations between adherence and clinical measures of disease activity and
      control. RESULTS: Among patients in all three disease groups, the proportion
      recalling recommendations to take prescribed medications (> or = 90%) exceeded
      the fraction recalling recommendations to follow a restricted diet, exercise
      regularly, and perform various self-care activities (22% to 84%). Adherence to
      recalled recommendations was similar across conditions but varied markedly
      according to the nature of the recommendations; for example, 91% of diabetics
      took prescribed medications but 69% followed a diabetics diet and 19% engaged in
      regular exercise. Adherence to recommendations was correlated with reduced serum
      glucose (r = -.33) and glycohemoglobin (r = -.25) levels among insulin-dependent
      diabetics and with reduced diastolic blood pressure among patients with
      hypertension (r = -.15). CONCLUSIONS: The majority of chronically ill patients
      failed to recall elements of potentially important medical advice and did not
      always adhere to advice that was recalled. Self-reported adherence was correlated
      with clinical measures of disease activity and control. Additional research is
      needed not only to improve adherence to medical advice in patients with chronic
      illnesses but also to determine which life-style changes are truly beneficial for
      these patients.

PMID- 8250649
TI  - Do the medical history and physical examination predict low lung function?
AB  - BACKGROUND: We sought to determine whether an abnormal respiratory history or
      chest physical examination could be used to identify men with low lung function.
      METHODS: We analyzed pulmonary function, physical examination, and questionnaire
      data from 4461 middle-aged male Vietnam-era army veterans. MAIN RESULTS: The
      study sample consisted of 1161 never smokers, 1292 former smokers, and 2008
      current smokers. Clinical indicators of respiratory disease (respiratory
      symptoms, respiratory signs, or a history of respiratory disease), were present
      in 26.1% of the never smokers, 31.7% of the former smokers, and 47.2% of the
      current smokers. We defined low forced expiratory volume in 1 second as a value
      less than 81.2% of the predicted value. Seven percent of the never smokers, 8% of
      the former smokers, and 17.3% of the current smokers demonstrated low forced
      expiratory volume in 1 second. Among those with a clinical indicator for
      spirometry only 11% of the never smokers, 13% of the former smokers, and 21% of
      the current smokers actually had a low forced expiratory volume in 1 second.
      Among those without a clinical indicator 6% of the never smokers, 6% of the
      former smokers, and 14% of the current smokers actually had a low forced
      expiratory volume in 1 second. CONCLUSIONS: The use of clinical indicators as a
      basis for obtaining pulmonary function tests in middle-aged men misses many with
      low lung function, especially current smokers.

PMID- 8250650
TI  - Staphylococcus aureus meningitis. A review of 104 nationwide, consecutive cases.
AB  - METHODS: Based on a nationwide registration, the clinical and bacteriologic data
      from 61 postoperative and 43 hematogenous cases of Staphylococcus aureus
      meningitis in Denmark from 1986 through 1989 were reviewed. RESULTS:
      Postoperative meningitis was a foreign body infection in 89% of the cases and had
      a lower mortality (18% [11/61]) compared with hematogenous meningitis (56%
      [24/43]). Hematogenous S aureus meningitis seems to be part of an overwhelming,
      disseminated infection as indicated by the following: 81% of the patients had
      bacteremia, 21% had endocarditis, and 12% had osteomyelitis. Most patients were
      older, often with underlying diseases, community-acquired infections, and a
      clinical picture of severe meningitis. The major findings were mental status
      changes and a high rate (34%) of focal neurological changes. The initial
      leukocyte count in the cerebrospinal fluid sample was low, and the bacteria were
      seen in Gram's stain smears in 40% of cases only. The prognosis was related to
      the age of the patients and the initial antibiotic treatment. Patients treated
      with penicillinase-stable penicillins in combination with fusidic acid may have a
      better prognosis. Three (12%) of 25 surviving patients had severe sequelae.
      CONCLUSIONS: Hematogenous S aureus meningitis is a severe disease with a high
      mortality related to age, presence of shock, and infection with strains of phage
      type 95.

PMID- 8250651
TI  - Fever among outpatients with advanced human immunodeficiency virus infection.
AB  - BACKGROUND: Fever is common among persons with human immunodeficiency virus (HIV)
      infection. However, the clinical implications of fever in this population have
      not been evaluated. We therefore undertook a prospective study of fever in
      persons with advanced HIV infection to determine the incidence and etiology of
      fever in this patient group. METHODS: Prospective natural history study of 176
      patients with advanced HIV infection followed up at Memorial Sloan-Kettering
      Cancer Center, New York, NY, from April 1, 1990, through December 31, 1990.
      RESULTS: Fever occurred in 46% of patients. A diagnosis was made in 83% of
      episodes, with acquired immunodeficiency virus-defining illnesses accounting for
      half of the diagnosed cases. Patients whose conditions required more than 2 weeks
      to diagnose most often had lymphoma, Mycobacterium avium-intracellulare
      bacteremia, or Pneumocystis carinii pneumonia. Four patients had persistent
      unexplained fever without a clear source. Only one patient had fever that clearly
      responded to antiretroviral therapy. CONCLUSIONS: Fever is common among
      outpatients with advanced HIV infection. Human immunodeficiency virus itself is
      rarely the cause of fever in such patients; the cause of the fever should be
      thoroughly evaluated.

PMID- 8250652
TI  - Medical students' exposure and immunity to vaccine-preventable diseases.
AB  - BACKGROUND: This study was conducted to assess medical students' immunity to
      vaccine-preventable diseases, their exposure to these diseases, and their
      attitudes toward immunity to vaccine-preventable diseases. METHODS: A cross
      sectional, mailed survey was conducted of all 249 senior medical students in the
      1991 graduating class at the University of Minnesota, Minneapolis. Two mailings
      were sent during the autumn of their senior year. RESULTS: The response rate was
      77.5%. More than 90% of the students reported that they were immune to measles,
      mumps, rubella, and hepatitis B but only 23% were immune to influenza. Fewer than
      half of the students had ever been queried about their immune status prior to
      clinical clerkships. One third of the students had had a needlestick exposure
      during their clinical training (including 8% to a known hepatitis B carrier) and
      only 52% of these were reported by the student. Ten percent to 20% of the
      students felt that immunity to measles, mumps, and rubella was only somewhat or
      not very important. Less than one third of the students felt that immunity to
      influenza was important for themselves as health care providers. CONCLUSION: This
      study documented inadequate levels of immunity among medical students to certain
      vaccine-preventable diseases, that exposure to vaccine-preventable diseases was
      fairly common during clinical training, and that medical students often had
      inadequate attitudes about immunity to vaccine-preventable diseases. These
      findings have implications for medical school immunization policies and
      curriculum content.

PMID- 8250653
TI  - The nicotine patch in smoking cessation. A randomized trial with telephone
      counseling.
AB  - BACKGROUND: This study was conducted to determine the efficacy of the nicotine
      patch in smoking cessation when combined with self-help materials, three brief
      visits, and telephone counseling. METHODS: One hundred fifty-nine healthy
      volunteers who smoked at least one pack of cigarettes per day and desired to quit
      smoking were enrolled in a double-blind trial with 6-week treatment and 6-month
      follow-up periods. After review of self-help materials, subjects were randomly
      assigned to regimens of nicotine or placebo patches. Subjects wore two patches
      per day for 4 weeks (25 mg of nicotine per 24 hours), then one patch per day for
      2 weeks. Return visits were at the ends of weeks 4 and 6. Telephone counseling
      was given during weeks 1, 2, 3, and 5. Abstinence at 6 weeks was defined as zero
      cigarettes smoked for the previous 28 days, verified by exhaled carbon monoxide
      less than 8 ppm at 4 weeks and 6 weeks. Abstinence at 3 and 6 months was defined
      as self-report of zero cigarettes since the previous contact, verified by carbon
      monoxide value at 6 months. RESULTS: Abstinence rates at 6 weeks, 3 months, and 6
      months were 29.5%, 21.8%, and 20.5% in the active group, and 8.8%, 3.8%, and 2.5%
      in the placebo group (P < or = .001 for each comparison), respectively. Skin
      irritation was the main side effect, causing 1.3% to drop out. CONCLUSION: The
      nicotine patch is efficacious in smoking cessation over a 6-month period, when
      combined with only self-help materials, three brief visits, and telephone
      counseling.

PMID- 8250654
TI  - Case management and plasma half-life in a case of brodifacoum poisoning.
AB  - Brodifacoum is a readily available, second-generation anticoagulant rodenticide
      (superwarfarin) that causes extended depletion of vitamin K1-dependent clotting
      factors. Brodifacoum ingestions are being reported with increasing frequency. For
      the first time, we compare plasma brodifacoum concentration to prothrombin levels
      over time in a case of brodifacoum poisoning. Brodifacoum was eliminated
      according to a two-compartment model, with an initial half-life of 0.75 days and
      a terminal half-life of 24.2 days. On admission, the brodifacoum level was 731
      micrograms/L and the patient suffered severe urinary tract hemorrhage, requiring
      transfusion of blood products. Persistently increased prothrombin times
      necessitated treatment with phytonadione up to 80 mg/d for 4 months, until the
      brodifacoum level reached 10 micrograms/L. These data may help project the
      duration of phytonadione treatment required in future cases of brodifacoum
      poisoning. Superwarfarin exposure must be suspected in an otherwise unexplained
      vitamin K1-deficient coagulopathy.

PMID- 8250655
TI  - Oral anticoagulant therapy.

PMID- 8250656
TI  - The utility of the rheumatoid factor.

PMID- 8250657
TI  - The low-probability lung scan. A potentially lethal reading.

PMID- 8250658
TI  - The Orphan Drug Act. Should it be changed?

PMID- 8250659
TI  - Coronary artery disease in women. Risk factors, evaluation, treatment, and
      prevention.
AB  - Cardiovascular disease is the leading cause of death in women. Unfortunately, the
      problem of cardiovascular disease in women has been largely ignored as women have
      been enrolled in limited numbers or excluded entirely from many of the major
      trials on which treatment of cardiovascular disease have been based. Furthermore,
      recent evidence suggests that a gender bias against aggressive intervention and
      treatment of cardiovascular disease in women may exist. This article reviews the
      risk factors, methods of identification, and treatment of coronary artery disease
      in women, as well as the potential benefits of postmenopausal estrogen.

PMID- 8250660
TI  - Silicone breast implants. History, safety, and potential complications.
AB  - The purpose of this study is to review the background, safety, and potential
      complications of silicone breast implants. Relevant studies were identified using
      a MEDLINE search of the English-language literature, followed by a manual search
      of the references of all identified articles and a review of abstracts from the
      1992 American College of Rheumatology meeting. Review of the literature suggests
      that silicone does not appear to fulfill the characteristics of an ideal
      synthetic soft-tissue substitute, although it may be the best substitute
      available. Silicone breast implants are associated with local inflammation and
      tissue fibrosis with breast fibrous capsule contracture developing in 10% to 40%
      of the patients. There are no epidemiologic data that establish a direct link
      between silicone and cancer or rheumatic disease. However, scleroderma appears to
      be overrepresented among the published articles on patients with silicone breast
      implants and rheumatic disease. Autoantibodies of unclear significance may be
      found in 5% to 30% of women with silicone breast implants. Large, longitudinal,
      population-based studies that include patients who have had implants for 5 to 15
      years may be necessary to fully understand the relationship of silicone implants
      and immune dysfunction.

PMID- 8250661
TI  - Practice guidelines: a new reality in medicine. III. Impact on patient care.
AB  - Practice guidelines are being introduced throughout medicine, but expectations
      about their impact on patient care depend on whether one is a clinician, patient,
      payer, administrator, or politician. Proponents hope that guidelines will enhance
      the knowledge, attitudes, and behavior of practitioners and will optimize health
      outcomes, costs, and malpractice decisions, but scientific evidence of these
      effects is limited. There are also concerns that guidelines could harm patient
      care. Clinicians worry that guidelines will promote "cookbook medicine," decrease
      their autonomy and income, and increase medicolegal liability. A particular
      concern relates to the expansion of enforcement programs that require clinicians
      to follow guidelines or face financial or other penalties. Guidelines can rarely
      define optimal care with certainty, due to poor science, imperfect analytic
      processes, and differences in patients. Recommendations are often worded in
      highly specific language that achieves clarity at the expense of scientific
      validity. Rigid enforcement of such guidelines could harm patients, interfere
      with the individualization of care, increase costs, and promote unfair judgments
      against clinicians who deviate from them for good reasons. A model that links the
      intensity of enforcement to the scientific and clinical quality of guidelines is
      proposed.

PMID- 8250662
TI  - Recombinant human erythropoietin treatment: investigational new drug protocol for
      the anemia of the acquired immunodeficiency syndrome. Overall results.
AB  - BACKGROUND: Anemia associated with human immunodeficiency virus infection may be
      due to reduced erythropoiesis related to the disease itself or to concomitant
      medications (eg, zidovudine). Clinical studies have shown recombinant human
      erythropoietin (r-HuEPO) to be effective in correcting the anemia of zidovudine
      treated patients infected with human immunodeficiency virus with baseline serum
      erythropoietin levels of 500 U/L or less. A treatment investigational new drug
      protocol that provided r-HuEPO to 1943 anemic patients with the acquired
      immunodeficiency syndrome was studied. METHODS: Enrollment criteria included a
      clinical diagnosis of acquired immunodeficiency syndrome, serum erythropoietin
      level of 500 U/L or less, hematocrit less than 0.300, and age of 12 years or
      more. The initial r-HuEPO dosage was 4000 U subcutaneously for 6 days each week.
      On the basis of response, the r-HuEPO dosage could be increased sequentially to
      8000 U subcutaneously for 6 days per week. This was an open-label multicenter
      treatment protocol. A total of 1943 patients were treated by 510 investigators.
      Efficacy evaluations were based on the effect of r-HuEPO on hematocrit levels and
      transfusion requirements relative to baseline. Adverse experiences that were
      considered by the investigator to be possibly related to r-HuEPO therapy were
      collected to assess safety. RESULTS: Therapy with r-HuEPO resulted in an increase
      in mean hematocrit from a baseline of 0.280 to 0.331 at week 12 and 0.338 at week
      24. This increase was sustained throughout the course of the study to week 54.
      Overall, 40% of patients (769/1943) required at least one transfusion in the 6
      week interval immediately preceding study entry (baseline). After 12 and 24 weeks
      of r-HuEPO treatment, corresponding percentages were 22% (311/1387) and 18%
      (119/650), respectively. Response to therapy, defined as an increase of 0.060
      from baseline in hematocrit, with no transfusions within 28 days before achieving
      that hematocrit, was observed in 44% of patients. Adverse experiences not clearly
      related to acquired immunodeficiency syndrome were reported by 11% of patients.
      CONCLUSION: In a study population of 1943 anemic patients with acquired
      immunodeficiency syndrome treated with r-HuEPO, the hematocrit increased and
      blood transfusion requirements decreased. Therapy with r-HuEPO was well
      tolerated.

PMID- 8250663
TI  - A comparison of Streptococcus pyogenes (group A streptococcal) bacteremia at an
      urban and a suburban hospital. The importance of intravenous drug use.
AB  - BACKGROUND: There has been a recent resurgence of severe infections with
      Streptococcus pyogenes, including bacteremias and a toxic shock-like syndrome.
      The purpose of this study was to examine the influence of intravenous drug use on
      the incidence, clinical epidemiology, and severity of S pyogenes bacteremia.
      METHODS: We conducted a retrospective survey of medical records at a 500-bed
      tertiary care urban hospital and at a nearby 500-bed suburban university
      affiliated hospital. All patients from each hospital with documented S pyogenes
      bacteremia from January 1, 1979, to December 31, 1989, were included. We examined
      demographic and clinical data from cases at the two institutions, serologic
      findings from a subset of isolates from the urban hospital, and factors
      associated with mortality from S pyogenes bacteremia by stepwise logistic
      regression analysis. RESULTS: Ninety-five cases of S pyogenes bacteremia were
      identified, with 65% (62 cases) occurring at the urban center. Intravenous drug
      use occurred more frequently at the urban center (P < .005); the injecting drug
      users were significantly younger than the non-drug-using population (P = .001).
      Infection with the human immunodeficiency virus occurred in a subset of the
      injecting drug users at the urban center. Cellulitis and cutaneous abscesses were
      the most common sources of bacteremia at both centers. During the study period,
      the numbers of S pyogenes bacteremias increased at the urban center (P = .007),
      accompanied by a significant increase in the proportion of infections associated
      with parenteral drug use (P = .003). There was no change in the prevalence of any
      T type throughout the study period and no clustering of T types among injecting
      drug users. The overall mortality was 23% (20/89). By logistic regression
      analysis, age older than 65 years (relative risk [RR], 14; 95% confidence
      interval [CI], 3.2 to 68) and the presence of the toxic shock-like syndrome (RR,
      36; 95% CI, 2.2 to 600) were significantly associated with mortality due to S
      pyogenes bacteremia. CONCLUSIONS: Intravenous drug use accounted for an increase
      in cases of S pyogenes bacteremia at an inner-city hospital. However, advanced
      age and the toxic shock-like syndrome were the most important predictors of
      mortality.

PMID- 8250664
TI  - Lack of association of human immunodeficiency virus seroconversion with visits to
      foreign ports in US Navy personnel.
AB  - BACKGROUND: The US Navy visits ports on all continents and many islands of the
      world, many of which are reported to have a high endemicity of human
      immunodeficiency virus (HIV) infection. The objective of this study was to
      determine whether visits to foreign ports by active-duty navy personnel were
      associated with increased risk of HIV infection. METHODS: The Naval Health
      Research Center in San Diego, Calif, maintains records of all HIV enzyme-linked
      immunosorbent assay and Western blot tests given in the navy. This information,
      along with career histories and ship movement data, was used in a nested case
      control design to examine the relationship between visits to the 100 foreign
      ports most frequently visited by the navy and risk of HIV seroconversion. All
      visits to a port and total time in each port during the study period were
      examined. A total of 813 seroconverters were matched to 6993 seronegative active
      duty controls by age, race, sex, occupational group, home port, and year of test.
      RESULTS: Estimated relative risks of seroconversion associated with visits to
      foreign ports showed no statistically significant excess risk of HIV infection
      for navy personnel after visits to any foreign port. CONCLUSIONS: These results
      do not imply that an individual's risk of acquisition of HIV would be less in a
      foreign port if the individual engaged in high-risk activity there. Rather, they
      imply that despite the mobility of the US Navy and the large variation in HIV
      seroprevalence rates throughout the world, navy personnel generally do not appear
      to be acquiring HIV infections abroad.

PMID- 8250665
TI  - Tuberculosis in a correctional facility.
AB  - BACKGROUND: After the identification of five suspected cases of tuberculosis (TB)
      in a Nassau County (New York) jail during a 3-week period, an epidemiologic
      investigation was begun to document the number of cases of TB infection and
      disease associated with the jail, the characteristics of current or former
      inmates with TB disease, and the factors contributing to TB transmission in the
      jail. METHODS: The county TB register was matched against the inmate files of the
      jail. Medical records from hospitals, the health department, and the jail were
      then reviewed. All inmates in the jail were skin tested during a mass screening.
      RESULTS: From January 1, 1988, through March 16, 1990, of 205 TB cases in the
      county, 49 (24%) were associated with the jail. Forty of the cases occurred among
      current or former inmates, one in a corrections officer, and eight among
      community contacts of inmates. The 40 inmates with TB were predominantly nonwhite
      (75%), unmarried (80%) men (90%), with a median age of 32 years. Twenty-three
      (58%) had a history of injecting drug use, and 14 (35%) were known to be
      seropositive for the human immunodeficiency virus. Thirty (75%) of the inmates
      had culture-confirmed pulmonary TB. Five (29%) of 17 Mycobacterium tuberculosis
      isolates had the same phage type and DNA fingerprint, which was consistent with
      transmission of infection within the jail. The mass screening revealed that 374
      (20%) of 1855 inmates were tuberculin positive. CONCLUSIONS: Without an effective
      program of TB control, jails can act as reservoirs of disease for inmates and
      staff, and for the community into which the inmates are released.

PMID- 8250666
TI  - Indium 111-monoclonal antimyosin antibody and magnetic resonance imaging in the
      diagnosis of acute Lyme myopericarditis.
AB  - BACKGROUND: Lyme borreliosis is a tick-borne multisystem disorder that may
      present as self-limiting early or persistent chronic diseases of the skin,
      nervous system, joints, heart, and other organs. Cardiac involvement has mainly
      been reported as acute atrioventricular conduction disturbances or transient
      ventricular dysfunction. METHODS AND RESULTS: We treated a patient with clinical
      signs of acute myopericarditis and serologic evidence of Lyme borreliosis
      confirmed by silver staining of endomyocardial biopsy specimens and indium 111
      monoclonal antimyosin antibody scan, which we believe has not been reported
      previously. Additionally, magnetic resonance imaging revealed epicardial and
      myocardial areas of increased intensity. CONCLUSION: Indium 111-monoclonal
      antimyosin antibody scanning and magnetic resonance imaging might play an
      additional important role in assessing and confirming the diagnosis of Lyme
      carditis in the presence of clinical symptoms and positive serologic findings.

PMID- 8250667
TI  - Ventricular fibrillation following adenosine administration. A case report.
AB  - An 86-year-old woman was treated for atrial fibrillation. A total of 1.00 mg of
      digoxin and 12.5 mg of verapamil hydrochloride were administered intravenously
      during an 8-hour period with no slowing of her heart rate, but the rhythm became
      regular. Subsequently, 15 mg of verapamil hydrochloride was administered
      intravenously during a 40-minute period with no reduction in heart rate.
      Adenosine (6 mg) was then administered intravenously. Approximately 20 seconds
      after adenosine infusion into a vein in the patient's right arm, a 2.2-second
      pause developed, followed by ventricular flutter and then fibrillation. The
      patient required resuscitation and defibrillation.

PMID- 8250668
TI  - Torsades de pointes associated with astemizole (Hismanal) therapy.

PMID- 8250669
TI  - Ciprofloxacin nephrotoxicity.

PMID- 8250670
TI  - Immunohistochemical localization of nerve growth factor (NGF) and NGF-receptor in
      the hypothalamus of adult rats.
AB  - In the adult mammalian central nervous system (CNS) the nerve growth factor (NGF)
      has thus far been associated mainly with the metabolic support and
      pathophysiology of cholinergic basal forebrain (CBF) neurons. Recently, however,
      the presence of NGF and NGF mRNA has been demonstrated in the hypothalamus of
      adult mice. In addition there have been reports on the stimulation of the
      pituitary-adrenocortical axis by NGF. These and other findings suggest the
      involvement of NGF in hypothalamic functioning. The aim of the present study was
      to improve immunohistochemical methodologies for the investigation of NGF and NGF
      receptor (NGF-r) in the hypothalamus of adult rats. Our results show NGF and NGF
      r expression in various regions of the hypothalamus. Moreover, in some areas,
      distribution and morphology of immunoreactive neurons suggest neuronal
      colocalization of the two markers. To study the function of NGF in the
      hypothalamus, anti-NGF antibody was injected in the area of the paraventricular
      nucleus. We did not, however, find an effect of treatment on NGF-r immunoreactive
      neurons in this area.

PMID- 8250671
TI  - Physical and optical shelter characteristics influence rat's preferences in a
      multiple Y-maze.
AB  - Rat's preference for covered or uncovered sections of a multiple Y-maze, measured
      as time spent under cover, was investigated. Surface area of covered and
      uncovered sections was the same. There were no light-intensity differences
      between uncovered and covered sections. Coverings were of two types: transparent
      or sanded plexiglas, affording respectively only physical or physical and optical
      protection. Both types of covering were placed either over discontinuous sections
      of the maze or continuously over one entire half of it. Male adult Wistar rats
      were employed. Rats exhibited maximal preference for the continuous sanded
      covering. They also exhibited a very similar significant preference for the
      continuous transparent covering and the discontinuous sanded one. Equal
      permanence time was measured in uncovered sections and under discontinuous
      transparent coverings. The results show that rats can recognize and choose
      shelter even when there is no light diminution under it. In fact they can very
      well discriminate between the several types of shelter, as shown by their
      significant longer permanence under the most protective and most continuous one.
      Finally, results are taken as basis for discussing whether the accepted "dark
      preference" of rats may be due solely to photophobia or also to the fact that
      normally darkness indicates a shelter.

PMID- 8250672
TI  - Functional properties of neurons in area V1 of awake macaque monkeys: peripheral
      versus central visual field representation.
AB  - The region of the striate cortex where the visual field is represented up to 52
      degrees from the fovea was explored in awake, behaving monkeys. Extracellular
      recordings were made from 241 neurons. On the basis of their receptive field
      position in the visual field, they were subdivided into a central (within 10
      degrees from the fovea) and a peripheral (beyond 10 degrees) group. Sensitivity
      to orientation, length, direction and velocity of movement of conventional light
      stimuli was tested and compared in the two samples. Besides the well-known
      increase of receptive field size with eccentricity, gross differences were found
      only for the sensitivity to the velocity of stimulus movement. The great majority
      of neurons in the central sample preferred slow velocities and showed no
      sensitivity to velocities above 100 degrees/sec. In contrast, many peripheral
      neurons were poorly sensitive to slow speeds of movement and well responsive to
      high velocities, above 100 degrees/sec. Cells that showed a better response to an
      actual stimulus movement in the visual field than to a retinal image movement
      self-induced by an eye-movement ("real-motion" cells) were also searched for in
      the two samples. They were found in the 13% of the central neurons and in the 25%
      of the peripheral neurons. Present data extend to the awake, behaving animal what
      already known from paralysed animal, indicating that in physiological conditions
      central and peripheral vision have a different functional role in the analysis of
      motion within the visual field.

PMID- 8250673
TI  - Neuropeptide Y in the carp torus semicircularis: an immunocytochemical study.
AB  - The presence of neuropeptide Y-like immunoreactivity in the torus semicircularis
      of the teleost fish Cyprinus carpio was studied using an indirect
      immunoperoxidase technique. In general, both the nuclei lateralis and centralis
      of the torus semicircularis showed a high density of immunoreactive fibers from
      rostral to caudal levels. In particular, in the nucleus lateralis a low density
      of immunoreactive fibers was only found in the subependymal layer, whereas this
      was high in the small cell, fibrillar and disperse cells layers. Similarly, the
      nucleus centralis showed a low density of immunoreactive fibers in the fibrillar
      cortex, and a high density in the cellular region. Moreover, a moderate density
      of fusiform or round-ovoid cell bodies containing neuropeptide Y-like
      immunoreactivity was found in the cellular region of the nucleus centralis. These
      neurons were located dorsally or near to the lateral lemniscus, and situated
      perpendicular, parallel or oblique to the surface, showing one or two long and
      relatively unbranching dendritic trunks. The localization of neuropeptide Y-like
      immunoreactivity in both nuclei--lateralis and centralis--of the carp torus
      semicircularis suggests that this peptide is involved in the control of visual,
      auditive, and lateral line mechanisms, as well as in the control of feeding.

PMID- 8250674
TI  - Fos-like immunoreactivity in the rat brain in spontaneous wakefulness and sleep.

PMID- 8250675
TI  - Risk of tryptophan depletion following amino acid supplementation.

PMID- 8250676
TI  - Euphorogenic properties of the serotonergic partial agonist m
      chlorophenylpiperazine in cocaine addicts.

PMID- 8250677
TI  - Transference interpretations, patients' gender, and dropout rates.

PMID- 8250678
TI  - Light therapy in seasonal affective disorder is independent of time of day or
      circadian phase.
AB  - OBJECTIVE: We tested the hypothesis that phase-delayed circadian rhythms underlie
      seasonal affective disorder (SAD) by measuring phase position of 6
      sulfatoxymelatonin excretion and comparing antidepressant response to morning or
      evening light given as a first treatment. DESIGN: Randomized controlled trial.
      SETTING: Ambulatory. PATIENTS: Thirty-two women and seven men with SAD.
      INTERVENTION: Light therapy (2500 lux for 1 hour for 1 week) was administered
      either at 7 AM or 10 PM, preceded by a baseline week and followed by a withdrawal
      week. RESULTS: Our SAD patient sample was moderately depressed (Hamilton
      Depression Scale [HAM-D] score 18); a HAM-D reduction of 50% or more was found in
      12 of 18 patients given morning and in 15 of 21 patients given evening light (70%
      response rate). Response was not dependent on age, gender, stage of the menstrual
      cycle, time of year, or on the timing or duration of sleep. Urinary 6
      sulfatoxymelatonin was measured in 30 patients; 22 had phase-delayed circadian
      rhythms. However, phase position was correlated neither with depth of depression
      nor with a preferential response to morning or evening light. COMMENT: Both
      morning and evening light therapy improved depressive symptoms in patients with
      SAD independent of their circadian phase or sleep timing. These findings argue
      against a circadian phase-delay hypothesis of the pathophysiology of SAD, or the
      necessity of a phase-advance by morning light for clinical efficacy. They
      additionally suggest more practicable and flexible schedules for light therapy in
      SAD, since time of day is not crucial.

PMID- 8250679
TI  - Prevalence of seasonal affective disorder in Iceland.
AB  - OBJECTIVE: To investigate seasonal patterns in mood and behavior and estimate the
      prevalence of seasonal affective disorder (SAD) and subsyndromal seasonal
      affective disorder (S-SAD) in the Icelandic population. PARTICIPANTS AND SETTING:
      A random sample generated from the Icelandic National Register, consisting of
      1000 men and women aged 17 to 67 years from all parts of Iceland. It represents
      6.4 per million of the Icelandic population in this age group. DESIGN: The
      Seasonal Pattern Assessment Questionnaire, an instrument for investigating mood
      and behavioral changes with the seasons, was mailed to a random sample of the
      Icelandic population. The data were compared with results obtained with similar
      methods in populations in the United States. MAIN OUTCOME MEASURES: Seasonality
      score and prevalence rates of seasonal affective disorder and subsyndromal
      seasonal affective disorder. RESULTS: The prevalence of SAD and S-SAD were
      estimated at 3.8% and 7.5%, respectively, which is significantly lower than
      prevalence rates obtained with the same method on the east coast of the United
      States (chi 2 = 9.29 and 7.3; P < .01). The standardized rate ratios for Iceland
      compared with the United States were 0.49 and 0.63 for SAD and S-SAD,
      respectively. No case of summer SAD was found. CONCLUSIONS: Seasonal affective
      disorder and S-SAD are more common in younger individuals and among women. The
      weight gained by patients during the winter does not seem to result in chronic
      obesity. The prevalence of SAD and S-SAD was lower in Iceland than on the East
      Coast of the United States, in spite of Iceland's more northern latitude. These
      results are unexpected since the prevalence of these disorders has been found to
      increase in more northern latitudes. The Icelandic population has remained
      remarkably isolated during the past 1000 years. It is conceivable that persons
      with a predisposition to SAD have been at a disadvantage and that there may have
      been a population selection toward increased tolerance of winter darkness.

PMID- 8250680
TI  - The prevalence of seasonal affective disorder is low among descendants of
      Icelandic emigrants in Canada.
AB  - OBJECTIVE: To examine whether a genetic selection within the Icelandic population
      helps it to adapt to the long arctic winter. PARTICIPANTS AND SETTING: The target
      population was a group of adults in the Interlake district of Manitoba, Canada,
      wholly descended from Icelandic emigrants. The ancestry of every individual in
      this group can be traced back to 1840. DESIGN: The Seasonal Pattern Assessment
      Questionnaire was mailed to a random sample of the study population. The data
      were compared with results obtained with similar methods in populations in
      Iceland and on the eastern seaboard of the United States. MAIN OUTCOME MEASURES:
      Prevalence rates of seasonal affective disorder and subsyndromal seasonal
      affective disorder. RESULTS: The prevalence rates of seasonal affective disorder
      and subsyndromal seasonal affective disorder were found to be 1.2% and 3.3%,
      respectively, in this group of Canadians of wholly Icelandic descent. These are
      significantly lower than those measured with similar methods among people living
      along the east coast of the United States (chi 2 = 12.6 and 14.4, respectively, P
      < .001). Standardized rate ratio for this group compared with the American group
      was 0.18 for seasonal affective disorder and 0.38 for subsyndromal seasonal
      affective disorder. CONCLUSIONS: This is the second study to find the prevalence
      of seasonal affective disorder and subsyndromal seasonal affective disorder to be
      lower among Icelanders or their descendants than among populations along the east
      coast of the United States. The results indicate that the relationship between
      prevalence of these disorders and geographic latitude is more complex than has
      previously been suggested; genetic adaptation in Icelandic populations may play
      an important role.

PMID- 8250681
TI  - The Roscommon Family Study. IV. Affective illness, anxiety disorders, and
      alcoholism in relatives.
AB  - OBJECTIVES: This report seeks to evaluate the specificity of the familial
      liability to schizophrenia by examining in the relatives of the various proband
      groups the risk for affective illness (AI), anxiety disorders, and alcoholism.
      DESIGN: A case-controlled epidemiologic family study using DSM-III-R criteria.
      PARTICIPANTS: Three hundred eighty-four index probands from a psychiatric case
      register, 150 unselected control probands from an electoral register and 2043 of
      their living and traceable relatives, of whom 1753 were personally interviewed.
      RESULTS: In personally interviewed relatives of schizophrenic probands, the
      lifetime risk for all AI (24.9% +/- 3.8%) or just bipolar AI (1.2% +/- 0.7%) was
      very similar to that found in interviewed relatives of controls (22.8% +/- 4.0%
      and 1.4% +/- 0.7%, respectively). However, the risk for all AI (49.7% +/- 12.9%)
      or bipolar AI (4.8% +/- 3.2%) was substantially increased in relatives of
      schizoaffective probands. A substantially higher proportion of relatives of
      schizophrenic vs control probands who had AI demonstrated psychotic--and
      specially mood-incongruent psychotic--symptoms when affectively ill. Neither the
      risk for anxiety disorders nor that for alcoholism was increased in relatives of
      schizophrenic vs control probands. CONCLUSIONS: The familial liability to
      schizophrenia possesses some specificity and does not substantially increase the
      risk to AI, anxiety disorders, or alcoholism. Even when narrowly defined,
      schizoaffective disorder has a substantial familial link to classic AI. The
      familial liability to schizophrenia predisposes to psychosis, and especially mood
      incongruent psychosis, when affectively ill. Finally, these results do not
      support the hypothesis that, from a familial perspective, schizophrenia and AI
      are on a single etiologic continuum.

PMID- 8250682
TI  - The validity of DSM-III-R hypochondriasis.
AB  - BACKGROUND: Because of the uncertainty about the status of hypochondriasis, the
      disorder is rarely diagnosed. To address this problem we examined the validity of
      DSM-III-R hypochondriasis as identified by structured interview. METHODS:
      Patients in a general medicine clinic were screened for hypochondriacal attitudes
      and symptoms. Those patients who scored above an established cutoff had a
      structured diagnostic interview, and 50 patients who met DSM-III-R criteria for
      hypochondriasis and 50 age- and sex-matched controls were thus identified.
      Information was obtained from both groups on health perceptions, health care
      utilization, and level of functioning using self-report and physician-rated
      measures. Additional information on diagnoses and treatment recommendations was
      obtained from record audits. RESULTS: Clinic physicians rated hypochondriacal
      subjects as having more unrealistic fear of illness (hypochondriasis) and
      diagnosed psychiatric and functional somatic syndromes more frequently in
      hypochondriacal than in control subjects. Hypochondriacal subjects viewed their
      health as worse, had more health worries, and had more severe psychiatric
      symptoms than control subjects. They also reported poorer physical functioning
      and work performance, greater health care utilization, poorer response to medical
      treatment, and less satisfaction with the care received than controls.
      CONCLUSIONS: Results show that, although the diagnosis of hypochondriasis is
      rarely made, physician recognition is high. They also show that several
      indicators of internal and external validity of this diagnostic category exist.
      Findings suggest that if physicians are to reduce the functional impairment and
      nonproductive health care utilization of these patients, they will need to make
      the diagnosis of hypochondriasis and intervene appropriately. However, for this
      to occur, research demonstrating predictive validity and treatment responsiveness
      of the disorder will be required.

PMID- 8250683
TI  - Naturalistic follow-up of a behavioral treatment for chronically parasuicidal
      borderline patients.
AB  - BACKGROUND: A randomized clinical trial was conducted to evaluate whether the
      superior performance of dialectical behavior therapy (DBT), a psychosocial
      treatment for borderline personality disorder, compared with treatment-as-usual
      in the community, is maintained during a 1-year posttreatment follow-up. METHODS:
      We analyzed 39 women who met criteria for borderline personality disorder,
      defined by Gunderson's Diagnostic Interview for Borderline Personality Disorder
      and DSM-III-R criteria, and who had a history of parasuicidal behavior. Subjects
      were randomly assigned either to 1 year of DBT, a cognitive behavioral therapy
      that combines individual psychotherapy with group behavioral skills training, or
      to treatment-as-usual, which may or may not have included individual
      psychotherapy. Efficacy was measured on parasuicidal behavior (Parasuicide
      History Interview), psychiatric inpatient days (Treatment History Interview),
      anger (State-Trait Anger Scale), global functioning (Global Assessment Scale),
      and social adjustment (Social Adjustment Scale--Interview and Social Adjustment
      Scale--Self-Report). Subjects were assessed at 6 and 12 months into the follow-up
      year. RESULTS: Comparison of the two conditions revealed that throughout the
      follow-up year, DBT subjects had significantly higher Global Assessment Scale
      scores. During the initial 6 months of the follow-up, DBT subjects had
      significantly less parasuicidal behavior, less anger, and better self-reported
      social adjustment. During the final 6 months, DBT subjects had significantly
      fewer psychiatric inpatient days and better interviewer-rated social adjustment.
      CONCLUSION: In general, the superiority of DBT over treatment-as-usual, found in
      previous studies at the completion of 1 year of treatment, was retained during a
      1-year follow-up.

PMID- 8250684
TI  - A psychobiological model of temperament and character.
AB  - In this study, we describe a psychobiological model of the structure and
      development of personality that accounts for dimensions of both temperament and
      character. Previous research has confirmed four dimensions of temperament:
      novelty seeking, harm avoidance, reward dependence, and persistence, which are
      independently heritable, manifest early in life, and involve preconceptual biases
      in perceptual memory and habit formation. For the first time, we describe three
      dimensions of character that mature in adulthood and influence personal and
      social effectiveness by insight learning about self-concepts. Self-concepts vary
      according to the extent to which a person identifies the self as (1) an
      autonomous individual, (2) an integral part of humanity, and (3) an integral part
      of the universe as a whole. Each aspect of self-concept corresponds to one of
      three character dimensions called self-directedness, cooperativeness, and self
      transcendence, respectively. We also describe the conceptual background and
      development of a self-report measure of these dimensions, the Temperament and
      Character Inventory. Data on 300 individuals from the general population support
      the reliability and structure of these seven personality dimensions. We discuss
      the implications for studies of information processing, inheritance, development,
      diagnosis, and treatment.

PMID- 8250685
TI  - Differential diagnosis of personality disorders by the seven-factor model of
      temperament and character.
AB  - We used multiaxial structured interviews and questionnaires to evaluate the
      ability of self-reports on seven personality dimensions to predict independent
      interview diagnoses of DSM-III-R personality disorders. We studied 136
      consecutive adult psychiatric inpatients, excluding those with psychosis, organic
      mental disorders, and severe agitation. Sixty-six patients had interview
      diagnoses of DSM-III-R personality disorders. Most also had mood disorders. We
      confirmed the hypotheses that self-reports of low self-directedness and
      cooperativeness strongly predicted the number of personality symptoms in all
      interview categories, whereas the other factors distinguished among subtypes as
      predicted. Self-directedness and cooperativeness also predicted the presence of
      any personality disorder by differentiating patients varying in risk from 11% to
      94%. Patients in clusters A, B, and C were differentiated by low reward
      dependence, high novelty seeking, and high harm avoidance, respectively. We
      conclude that low self-directedness and cooperativeness are core features of all
      personality disorders and are validly measured by the seven-factor Temperament
      and Character Inventory, but not the five-factor Neuroticism-Extraversion
      Openness inventory. Each DSM-III-R personality disorder category is associated
      with a unique profile of scores in the seven-factor model, providing an efficient
      guide to differential diagnosis and treatment.

PMID- 8250686
TI  - Improving accuracy in gynecologic cytology. Results of the College of American
      Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.
AB  - The College of American Pathologists Interlaboratory Comparison Program in
      Cervicovaginal Cytology (PAP) is a quarterly mailed glass-slide quality
      improvement program. This growing program started as a pilot in 1989 with 207
      laboratories. In 1991, 605 laboratories participated. The diagnostic menu is
      modified from the Bethesda System and divides referenced slides into a negative
      series (normal, infectious, and reactive) and a positive series of epithelial
      lesions. A facsimile option facilitates immediate educational feedback. The 1989
      through 1991 major discrepancy rate averaged 5%. The consensus laboratory
      response had higher concordance than either pathologist or cytotechnologist
      responses. Low-grade squamous intraepithelial lesion was the leading cause of
      false-negative participant response, while reactive/reparative change was the
      leading cause of false-positive response. Pathologist false-negative and false
      positive responses from group or large case-volume practices were significantly
      lower than those from solo or small case-volume practices. Cytotechnologists in
      multiple-technologist or large-volume laboratories had significantly lower false
      negative responses than solo technologists or those in low case-volume
      laboratories, but false-positive rates did not differ. Experienced participants
      had fewer major discrepancies. The Interlaboratory Comparison Program in
      Cervicovaginal Cytology illustrates the feasibility of a large, mailed glass
      slide program, and offers laboratories a continuous method for monitoring and
      improving performance in gynecologic cytology.

PMID- 8250687
TI  - Accidental fires in clinical laboratories.
AB  - The National Fire Protection Association, Quincy, Mass, estimates that 169 fires
      have occurred annually in health care, medical, and chemical laboratories. On the
      average, there are 13 civilian injuries and $1.5 million per year in direct
      property damage. Most fires in which the cause or ignition source can be
      identified originate in malfunctioning electrical equipment (41.6%) or in the
      facility's electrical distribution system (14.7%). The prevalence of fire safety
      deficiencies was measured in the College of American Pathologists Laboratory
      Accreditation Program. Of the 1732 inspected laboratories, 5.5% lacked records of
      electrical receptacle polarity and ground checks in the preceding year. Of these
      inspected laboratories, 4.7% had no or incomplete documentation of electrical
      safety checks on laboratory instruments. There was no evidence of quarterly fire
      exit drills in 9% of the laboratories. Deficiencies were also found in
      precautionary labeling (6.8%), in periodic review of safe work practices (4.2%),
      in the use of safety cans (3.7%), and in venting of flammable liquid storage
      areas (2.8%). Fire preparedness would be improved if all clinical laboratories
      had smoke detectors and automatic fire-extinguishing systems. In-service training
      courses in fire safety should be targeted to the needs of specific service areas.

PMID- 8250688
TI  - A festschrift honoring the retirement of Vernie A. Stembridge, MD.

PMID- 8250689
TI  - Vernie A. Stembridge, MD.

PMID- 8250690
TI  - Apoptosis and necrosis. Basic types and mechanisms of cell death.
AB  - Apoptosis and necrosis are two fundamental types of cell death. Current knowledge
      indicates that the key mechanism of apoptosis is endonuclease activation leading
      to internucleosomal double-stranded chromatin (DNA) breaks, whereas the key
      mechanism of necrosis is cell membrane damage. The initial alterations of
      cellular metabolism and electrolyte homeostasis induced by an injurious agent may
      activate at least four major pathways leading to loss of membrane integrity:
      membrane phospholipid degradation, production of amphipathic lipids, damage to
      the cytoskeleton, and generation of toxic oxygen species and free radicals. These
      insights point the way for further research to establish definitive causes of
      specific types of cell injury and cell death, and they provide important clues
      for the design of improved diagnostic approaches and therapeutic interventions.

PMID- 8250691
TI  - Comparative pathology of microsporidiosis.
AB  - The obligate intracellular protozoan parasites belonging to the phylum Microspora
      are ubiquitous. They parasitize insects and all five classes of vertebrates. Only
      one genus infects mammals and birds but at least four genera affect humans. Two
      genera have been isolated from human specimens and both infect experimental
      animals. Some genera (eg, Enterocytozoon and Pleistophora) seem to be limited to
      a very few tissues but others (Encephalitozoon and the Encephalitozoon-like genus
      Septata) can infect multiple organs. Lesions range from classic microgranulomas
      to foci of infected cells unaccompanied by any inflammatory response. The most
      commonly occurring microsporidia infection of man (Enterocytozoon bieneusi) is
      characterized by infection of enterocytes of the villus tips of the small
      intestine, accompanied by villus blunting, crypt hyperplasia, sloughing of
      infected villus tip cells, and increased numbers of intraepithelial lymphocytes.

PMID- 8250692
TI  - Cytogenetic evaluation of childhood neoplasms.
AB  - The cytogenetics of childhood neoplasms are reviewed. Chromosome abnormalities
      specific for various pediatric neoplasms can provide diagnostic, prognostic, and
      scientific information of value to the pathologist, clinician, and molecular
      biologist. Karyotypes of acute leukemia have independent prognostic significance.
      Chromosome aberrations associated with several of the small round blue-cell
      tumors of childhood can clarify the diagnosis. Recurring abnormalities in several
      tumors, such as hepatoblastomas, primitive neuroectodermal tumors, fibrosarcomas,
      and other tumor types, suggest interesting questions about pathogenesis and
      histogenetic relationships. Several tumor-specific chromosome aberrations, mostly
      in the acute leukemias, have been characterized at a molecular level.

PMID- 8250693
TI  - The role of T lymphocytes in pulmonary microbial defense mechanisms.
AB  - Understanding how lung immunity develops against pulmonary pathogens should lead
      to more rational approaches in vaccine design and to the use of recombinant
      cytokines in lung disease. T lymphocytes are central to the development of
      effective immune responses; therefore, understanding how lung immunity develops
      will require a study of how and where T cells respond to respiratory antigens.
      Our laboratory has helped define the phenotype and function of lung dendritic
      cells, which likely play an essential role in stimulating naive T cells to
      respond to antigens. We found that both interstitial and alveolar macrophages can
      regulate the function of these cells, the former to enhance activity, the latter
      to suppress. In addition, we developed a murine pulmonary infection model using
      the fungus, Cryptococcus neoformans, in which T-cell-mediated immunity is
      essential for effective host clearance of the organism. The role of T cells in
      this model is to recruit and activate effector cells to resolve the lung
      infection; both CD4 and CD8 T-cell subsets are required for optimal effector cell
      recruitment. These studies are summarized as examples of current approaches to
      understanding pulmonary immunity.

PMID- 8250694
TI  - Immunohistochemical and lectin dissection of the human nephron in health and
      disease.
AB  - Many renal diseases involving the tubular epithelium appear to preferentially
      affect certain nephron segments. While major portions of the nephron, such as
      proximal and distal convoluted tubules and collecting ducts, can be identified in
      the normal kidney, the distinction of diseased nephron segments can be difficult
      in tissue sections. Thus, to identify which nephron segments are involved in
      pathologic changes is usually impossible by routine histologic examination alone.
      Recently antibody and lectin probes that react with specific nephron segment
      specific epitopes and carbohydrates, respectively, have become available. Some of
      these antibodies and lectins can be used on formalin-fixed, paraffin-embedded,
      archival tissues. Because renal tubules appear to retain their nephron segment
      specific epitopes and glycoprotein moieties under most pathologic conditions,
      these nephron segment-specific tubular epithelial markers provide a method to
      study renal diseases involving the tubular system also in archival material. Such
      nephron segment-specific tubular epithelial markers are: the lectins,
      Tetragonolobus purpuras and Phaseolus vulgaris erythroagglutinin (proximal
      tubular markers); antibodies to low-molecular-weight cytokeratin (AE1/AE3);
      epithelial membrane antigen and the lectin Arachis hypogaea (distal nephron
      [distal convoluted tubule and collecting duct] markers); and antibodies to Tamm
      Horsfall protein (labeling the thick ascending limb of Henle). We review the
      application of these and other renal tubular epithelial markers in the normal
      kidney and in various renal diseases including cystic disease of the kidney,
      interstitial nephritis, tubular atrophy, acute tubular necrosis, myeloma cast
      nephropathy, and renal tumors.

PMID- 8250695
TI  - Diagnostic accuracy in cervicovaginal cytology.

PMID- 8250696
TI  - Microsporidia. Emerging pathogens in immunodeficient persons.

PMID- 8250697
TI  - Sudden infant death syndrome. Is it a cause of death?

PMID- 8250698
TI  - Multiple hamartoma syndrome with osteosarcoma.
AB  - Multiple hamartoma syndrome, also known as Cowden's disease, is a rare
      genodermatosis with characteristic mucocutaneous lesions associated with multiple
      internal abnormalities. We describe a patient having classic dermatologic
      manifestations of Cowden's disease and multiple neoplasia including follicular
      adenocarcinoma of the thyroid gland with lung metastasis, intraductal breast
      carcinoma within a fibroadenoma, and an osteosarcoma. To our knowledge, this is
      the first reported case of an osteosarcoma in Cowden's disease.

PMID- 8250699
TI  - Multiple plexiform tumorlets of the uterus.
AB  - Plexiform tumorlet is a rare lesion usually found in the myometrium and is
      believed to be a variant of epithelioid leiomyoma. Multiple plexiform tumorlets
      may have an infiltrative pattern and mimic endometrial stromal sarcoma. Only five
      cases of multiple plexiform tumorlets of the uterus have been reported, to the
      best of our knowledge. We now present the sixth case.

PMID- 8250700
TI  - Intravascular calcium deposits in a critically ill patient. Light- and electron
      microscopic findings.
AB  - We describe a case of a 2-year-old girl with an unusual finding of amorphous
      hematoxyphilic substance in the pulmonary and myocardial vascular lumina. The
      patient had a prolonged history of intestinal obstruction necessitating extended
      periods of total parenteral nutrition. The patient terminally had hypercalcemia
      with levels reaching 4.63 mmol/L. The intravascular substance stains strongly
      positive for calcium, and weakly positive for fibrin. Electron microscopy shows
      that the substance has a distinctive configuration suggestive of calcium
      hydroxyapatite crystals.

PMID- 8250701
TI  - Polymorphous low-grade adenocarcinoma of the parotid salivary gland.
AB  - Polymorphous low-grade adenocarcinoma is an unusual tumor that has been described
      as occurring in the minor salivary glands, particularly of the palate. To our
      knowledge, there is only one previous report that has documented the occurrence
      of this type of lesion in the major salivary glands. We describe an elderly
      patient with polymorphous low-grade adenocarcinoma arising in the parotid gland
      that was originally diagnosed as carcinoma ex pleomorphic adenoma.

PMID- 8250702
TI  - Reflections of a former editor.

PMID- 8250703
TI  - Breast conservation therapy without axillary dissection. A rational treatment
      strategy in selected patients.
AB  - PURPOSE: Patients with early stage breast cancer are being treated with adjuvant
      systemic therapy with increasing frequency regardless of the pathological status
      of the axillary lymph nodes. The purpose of this study was to determine the
      outcome for local regional control in patients treated with radiation therapy to
      the intact breast and regional lymph nodes without axillary dissection. PATIENTS
      AND METHODS: The patient population for this study consists of 327 patients with
      clinical stage I or II invasive breast cancer who were treated by lumpectomy
      alone without axillary dissection followed by radiation therapy to the intact
      breast and regional lymph nodes. Outcome for local regional control and survival
      is reported. RESULTS: As of December 1990, with a median follow-up of more than
      10 years, the overall 10-year survival rate was 71%. There were a total of eight
      regional nodal failures resulting in a 5-year actuarial nodal control rate of
      97%. Minimal morbidity was associated with this treatment policy. CONCLUSIONS:
      For selected patients undergoing breast preservation therapy, lumpectomy alone
      without axillary dissection followed by radiation therapy to the intact breast
      and regional lymph nodes results in a high rate of local regional control.
      Selected patients in whom the results of the axillary lymph node dissection will
      not influence decisions regarding systemic therapy are candidates for this
      approach.

PMID- 8250704
TI  - Effect of organ donor race on health team procurement efforts.
AB  - OBJECTIVE: To determine whether referral of potential organ donors is affected by
      race of the patient. DESIGN: Retrospective chart audit. SETTING: Regional trauma
      center serving a 50% African-American population. PATIENTS: Records of patients
      meeting organ procurement organization criteria were reviewed for evidence that
      (1) they had been identified as a potential organ donor, (2) the family had been
      approached about organ donation, and (3) the family had agreed to or refused
      organ donation. RESULTS: There were 620 deaths, 152 (24%) met all donor criteria,
      114 (75%) were identified as potential donors, 90 (59%) were approached for
      donation, and 35 (23%) were organ donors. Of the white patients, 84% (71/85) vs
      64% of the African-Americans (43/67) were identified as donors (P < .01); 69%
      (59) of the whites vs 46% (31) of the African-Americans were approached for
      donation (P < .01); and 28% (24) of the whites vs 16% (11) of the African
      Americans were organ donors (P < .086). CONCLUSIONS: Before and after controlling
      for cause of death, the risk that African-American donors would not be identified
      was more than 2.4 times greater than for whites (P < .01). No significant racial
      differences were noted in requests for suicide and homicide victims; for accident
      victims, significantly fewer requests were made of African-Americans. Efforts
      must be made to determine the dynamics of interaction between staff and donor
      families and to enhance health-care team members' abilities to identify donors
      and request donations from both races in stress-provoking situations.

PMID- 8250705
TI  - Long-term outcome in 87 patients with low-grade soft-tissue sarcoma.
AB  - OBJECTIVE: To describe the long-term clinical outcome of patients with low-grade
      soft-tissue sarcoma and identify factors that may predict or determine their
      prognosis. DESIGN: Retrospective chart review with multivariate analysis.
      SETTING: Large research hospital and referral center. PATIENTS: All patients
      treated between 1975 and 1990 at the National Cancer Institute (Bethesda, Md) who
      had a confirmed diagnosis of low-grade soft-tissue sarcoma. INTERVENTIONS:
      Surgery and radiation therapy. MAIN OUTCOME MEASURES: Local recurrence and
      overall survival. RESULTS: For patients with nonretroperitoneal lesions, overall
      survival was excellent, with a history of recurrence, a positive surgical margin,
      and an absence of adjuvant radiation therapy significantly associated with
      increased risks of local recurrence. Patients with retroperitoneal lesions not
      only had an increased risk of local recurrence, but significantly poorer overall
      survival. CONCLUSIONS: Low-grade soft-tissue sarcomas are associated with
      excellent overall survival, especially those confined to nonretroperitoneal
      sites. The risk of local recurrence after resection with negative margins and/or
      adjuvant radiation therapy is very low and most recurrences can be controlled
      with further therapy.

PMID- 8250706
TI  - Endocrine organ metastases in subjects with lobular carcinoma of the breast.
AB  - OBJECTIVE: To define the frequency and pattern of endocrine organ metastases in
      patients dying of invasive lobular carcinoma. DESIGN: Postmortem microscopic
      evaluation of the ovaries and adrenal, pituitary, thyroid, and parathyroid glands
      for breast cancer metastases. SETTING: Roswell Park Cancer Institute, Buffalo,
      NY, between 1971 and 1990. SUBJECTS: One hundred eighteen subjects who died of
      their cancer: 86 had infiltrating ductal carcinoma; 32, invasive lobular
      carcinoma. MEAN OUTCOME MEASURE: Quantitative measurements to allow frequency
      determinations and statistical comparisons. RESULTS: Endocrine organ metastases
      were found in 91% of the subjects with invasive lobular carcinoma vs 58% of
      subjects with infiltrating ductal carcinoma. The adrenal gland was most
      frequently involved. Multiple endocrine metastases were most common in the group
      with invasive lobular carcinoma. CONCLUSIONS: A relationship exists between
      invasive lobular carcinoma and endocrine metastases. This indicates that
      antemortem endocrine evaluation may subsequently improve quality-of-life
      treatment.

PMID- 8250707
TI  - Airway pressure release ventilation.
AB  - BACKGROUND: Elevated airway pressures during mechanical ventilation are
      associated with hemodynamic compromise and pulmonary barotrauma. We studied the
      cardiopulmonary effects of a pressure-limited mode of ventilation (airway
      pressure release ventilation) in patients with the adult respiratory distress
      syndrome. METHODS: Fifteen patients requiring intermittent mandatory ventilation
      (IMV) and positive end-expiratory pressure (PEEP) were studied. Following
      measurement of hemodynamic and ventilatory data, all patients were placed on
      airway pressure release ventilation (APRV). Cardiorespiratory measurements were
      repeated after a 2-hour stabilization period. RESULTS: During ventilatory support
      with APRV, peak inspiratory pressure (62 +/- 10 vs 30 +/- 4 cm H2O) and PEEP (11
      +/- 4 vs 7 +/- 2 cm H2O) were reduced compared with IMV. Mean airway pressure was
      higher with APRV (18 +/- 5 vs 24 +/- 4 cm H2O). There were no statistically
      significant differences in gas exchange or hemodynamic variables. Both cardiac
      output (8.7 +/- 1.8 vs 8.4 +/- 2.0 L/min) and partial pressure of oxygen in
      arterial blood (79 +/- 9 vs 86 +/- 11 mm Hg) were essentially unchanged.
      CONCLUSIONS: Our results suggest that while airway pressure release ventilation
      can provide similar oxygenation and ventilation at lower peak and end-expiratory
      pressures, this offers no hemodynamic advantages.

PMID- 8250708
TI  - Nosocomial pneumonia during stress ulcer prophylaxis with cimetidine and
      sucralfate.
AB  - BACKGROUND: Recent studies have questioned the use of histamine (H2) receptor
      antagonist in stress ulcer prophylaxis because of an increased incidence of
      nosocomial pneumonia and subsequent death. DESIGN: This prospective randomized
      study compared prophylaxis with cimetidine vs sucralfate. SETTING:
      Medical/surgical intensive care unit in Springfield, Mass. PATIENTS: One hundred
      fourteen patients were enrolled. INTERVENTIONS: Cimetidine, administered as a
      primed continuous infusion using a 300-mg bolus followed by 37.5 mg/h, was
      compared with sucralfate, administered via nasogastric tube, at a dosage of 1 g
      every 6 hours suspended in 20 mL of sterile water. MAIN OUTCOME MEASURES: End
      points of the study included nosocomial pneumonia, gastrointestinal hemorrhage,
      and death. RESULTS: Fifty-six patients were randomized to receive cimetidine and
      their rate of pneumonia was 12.5%; upper gastrointestinal hemorrhage, 3.6%; and
      mortality, 33.9%. Fifty-eight patients were given sucralfate, and their rate of
      pneumonia was 13.8%; upper gastrointestinal hemorrhage, 3.4%; and mortality,
      37.9%. There were no significant differences between these study end points. In
      patients who had pneumonia, 80% of isolates were aerobic gram-negative bacilli.
      CONCLUSIONS: These observations suggest that the rate of nosocomial pneumonia is
      not increased in patients in the intensive care unit who receive prophylaxis with
      cimetidine to prevent stress ulcer bleeding.

PMID- 8250709
TI  - Hepatic abscess in cancer patients. Characterization and management.
AB  - OBJECTIVE: To identify factors that may aid in the diagnosis and treatment of
      patients with malignant neoplasms in whom hepatic abscesses develop. DESIGN:
      Retrospective review of medical records. PATIENTS: Thirty-seven oncology patients
      in whom hepatic abscesses developed at the National Cancer Institute, Bethesda,
      Md, between June 1954 and October 1989. RESULTS: Among 37 cancer patients,
      bacterial abscesses developed in 17 and fungal abscesses developed in 20. Among
      the patients with bacterial abscesses, 12 (71%) had a solid-tissue malignant
      neoplasm, 10 (59%) had a prior invasive procedure, and six (35%) had prior
      chemotherapy. In comparison, among the patients with fungal abscesses, 15 (75%)
      had a hematologic malignant neoplasm and five (25%) had a solid-tissue malignant
      neoplasm (P2 = .014). Two patients with fungal abscesses (10%) had a prior
      invasive procedure (P2 = .004) and 19 (95%) had prior chemotherapy (P2 < .0001).
      As compared with fungal abscesses, bacterial abscesses were larger (P2 < .00001)
      and fewer (P2 = .004). Antibiotics and percutaneous or surgical drainage
      effectively treated bacterial abscesses. Amphotericin B usually eradicated
      hepatic fungal infections. CONCLUSIONS: The results of this study reveal the
      importance of the clinical setting in the diagnosis of hepatic abscesses in
      cancer patients. Aggressive treatment of these abscesses is indicated and is
      frequently effective.

PMID- 8250710
TI  - Comparison of different techniques of stapled bowel anastomoses in a canine
      model.
AB  - OBJECTIVE: To evaluate different methods of creating a stapled enteroanastomosis
      and to determine which method would create a larger anastomosis. DESIGN:
      Prospective comparison of three groups with a total of 17 mongrel dogs. SETTING:
      Clinical investigation facility. MAIN OUTCOME MEASURES: Stapled side-to-side
      enteroanastomoses were created with the stapled edges touching or separated.
      Anastomoses were created in both functional bowel and in a defunctionalized limb.
      The anastomotic circumference was measured in a blinded fashion after 28 days.
      The third group had anastomoses created and measured the same day. Groups were
      compared using the t test. RESULTS: There was significant narrowing after healing
      with both types of anastomoses. Anastomoses created by separating the stapled
      lines were larger than those fashioned with the cut edges touching, both
      immediately and after healing. CONCLUSIONS: While clinically significant
      narrowing of a stapled anastomosis is uncommon, separating the staple lines of a
      functional end-to-end anastomosis may be the preferable method.

PMID- 8250711
TI  - The success of duplex ultrasonographic scanning in diagnosis of extremity
      vascular proximity trauma.
AB  - OBJECTIVE: To determine if duplex ultrasonographic scanning is diagnostically
      equivalent to arteriography and/or operative exploration in the diagnosis of
      extremity vascular proximity trauma. DESIGN: A prospective evaluation comparing
      duplex scanning with arteriography or operative exploration in 50 patients.
      Subsequently, duplex scanning was used alone for 175 extremity vascular proximity
      injuries, with other diagnostic methods used when injury was indicated on the
      duplex scan. SETTING: A busy urban trauma center. PATIENTS: Consecutive sample of
      200 patients with 225 extremity injuries. SELECTION CRITERIA: Vascular proximity
      injury or diminished strength of the extremity pulse. MAIN OUTCOME MEASURES: The
      presence or absence of vascular proximity injury confirmed on angiography and/or
      operative exploration. RESULTS: Duplex scanning had 100% sensitivity and 100%
      specificity compared with arteriography and/or operative exploration in the first
      50 cases. In the remaining 175 cases of extremity trauma, vascular injuries were
      diagnosed with duplex scanning alone. Duplex scanning detected 18 injuries, 17 of
      which were confirmed by correlation with arteriograms and/or operative
      exploration. One false-positive result--spasm of the superficial femoral artery-
      was found on arteriography. Seven unsuspected venous injuries were also
      diagnosed. CONCLUSIONS: Duplex scanning is a noninvasive, safe, effective method
      for the initial evaluation of potential extremity vascular proximity injury. It
      has replaced arteriography in the initial diagnosis of extremity vascular
      proximity trauma by our trauma service.

PMID- 8250712
TI  - Images of estrogen-receptor-positive breast tumors produced by estradiol labeled
      with iodine I 123 at 16 alpha.
AB  - OBJECTIVE: To examine the suitability of estradiol labeled with iodine I 123 at
      16 alpha for imaging estrogen-receptor-positive breast carcinoma using imaging
      instrumentation that is widely available. DESIGN: Single-photon emission computed
      tomographic imaging survey of 29 women with suspected primary or expected
      recurrent breast carcinoma. SETTING: University-based referral center.
      PARTICIPANTS: Twenty-nine women undergoing diagnosis for primary or recurrent
      breast carcinoma. Selection was voluntary. MAIN OUTCOME MEASURE: Qualitative
      imaging study designed to provide tomographic data of radioligand retention and
      descriptive data of imaging results. RESULTS: Single-photon emission computed
      tomographic imaging using 123I-estradiol at 16 alpha was performed for patients
      with breast carcinoma. Independent readers, without knowledge of receptor status
      or proven disease, interpreted the films. Scintigraphic detection was most
      noteworthy in patients with chest wall tumors and inflammatory breast cancer.
      Agreement between readers was 98% for true-negative readings and 94% for true
      positive readings, but only 60% for false-positive and false-negative film
      readings. CONCLUSIONS: Our results indicated that areas shown on imaging were
      also found to have estrogen-receptor activity and that radioligand accumulation
      can occur with low frequency in some surgically explored tissue. Radioligand
      imaging with 16 alpha-123I-estradiol can locate estrogen-receptor-positive breast
      tumors, including some that may be difficult to detect using conventional
      diagnostic imaging.

PMID- 8250713
TI  - Prognostic significance of the proliferation index in surgically resected non
      small-cell lung cancer.
AB  - OBJECTIVE: To determine the utility of measuring the tumor proliferation index as
      a prognostic marker in patients with non-small-cell lung cancer. DESIGN:
      Immunostaining for the proliferation-associated antigen Ki-67, quantitated using
      computer-assisted image cytometry, was used to derive the tumor proliferation
      index for 61 fresh-frozen, banked specimens of non-small-cell lung cancer. DNA
      ploidy was measured concomitantly for all specimens. A median follow-up of 38
      months was achieved for survival analyses. SETTING: A large southeastern United
      States private referral institution and affiliated hospital provided the study
      environment. PARTICIPANTS: A consecutive, convenience sample of 61 patients was
      enrolled based on resected tissue preservation and viability over a five-year
      accruement. MAIN OUTCOME MEASURES: Significant associations between DNA content,
      proliferation index, established clinicopathological parameters, and outcome were
      examined. RESULTS: A significant inverse association between patient survival and
      tumor proliferation index was found that was independent of other established
      clinicopathological predictors of outcome. Patients whose tumors harbored a
      proliferation index of less than 3.5 survived significantly longer than patients
      with tumors demonstrating higher values. No association between DNA content and
      proliferation index was uncovered. CONCLUSION: Measurement of the proliferation
      index, as derived from quantitative Ki-67 immunostaining and analyzed by image
      cytometry, may provide significant complementary, if not independent, prognostic
      information for patients with non-small-cell lung cancer.

PMID- 8250714
TI  - Neurologic degeneration associated with nitrous oxide anesthesia in patients with
      vitamin B12 deficiency.
AB  - Vitamin B12 (cyanocobalamin) is an integral component of two biochemical
      reactions in man: the conversion of L-methylmalonyl coenzyme A into succinyl
      coenzyme A and the formation of methionine by methylation of homocysteine. The
      transmethylation reaction is essential to DNA synthesis and to the maintenance of
      the myelin sheath by the methylation of myelin basic protein. Active vitamin B12
      contains cobalt in its reduced form (Co+). Nitrous oxide produces irreversible
      oxidation to the Co++ and Co forms that renders vitamin B12 inactive. Five cases
      (four from the literature and one new case) are presented in which patients
      unsuspected of having vitamin B12 deficiency developed subacute combined
      degeneration of the spinal cord following nitrous oxide anesthesia. Patients with
      vitamin B12 deficiency are exceedingly sensitive to neurologic deterioration
      following nitrous oxide anesthesia. If unrecognized, the neurologic deterioration
      becomes irreversible and may result in death.

PMID- 8250715
TI  - Resection of primary schwannoma of the liver not associated with
      neurofibromatosis.
AB  - A 38-year-old woman developed right upper quadrant pain due to a mass in the left
      lobe of the liver. The tumor was resected along with segment 3 of the left lobe.
      Histologic examination and immunochemistry supported a diagnosis of benign
      schwannoma. No metastatic disease was present, and the patient has been well for
      more than 18 months after surgery without recurrence. This is the first reported
      case of successful resection of a schwannoma of the liver in a patient without
      von Recklinghausen's disease.

PMID- 8250716
TI  - Management of small soft-tissue sarcoma of the extremity in adults.

PMID- 8250717
TI  - Comments on lessons learned.

PMID- 8250718
TI  - [Immunity and cell adhesion molecules].

PMID- 8250719
TI  - [Pharmacokinetics and pharmacodynamics of hydrocortisone in asthmatic children].
AB  - Corticosteroids are very efficacious in the treatment of asthma. In the present
      study, the conversion rate of hydrocortisone succinate (HCS) to hydrocortisone in
      plasma was examined and pharmacokinetic study was carried out for the two
      compounds after a single intravenous injection of hydrocortisone sodium succinate
      (HCSS). Moreover, it was examined whether hydrocortisone improved acute asthmatic
      attacks. In a randomised cross-over trial at 5 to 7 days intervals, 10 asthmatic
      children aged 9-14 years were treated with a single intravenous injection of HCSS
      in a dose of 5 mg hydrocortisone/kg body weight or without HCSS. After 4-hour
      pulmonary function studies, they were received a subcutaneous injection of
      epinephrine (0.004 mg/kg). The plasma concentrations of HCS and hydrocortisone
      were measured by the HPLC and/or radioimmunoassay. The mean of maximum
      concentration of HCS was 26.38 mg/L. The concentration of HCS decreased rapidly
      with a half-life of 0.09 hr (5.38 min). The concentration of hydrocortisone
      reached to a peak value of 4.96 mg/L after 10 min, and then decreased with a half
      life of 1.24 hour. It is predicted that an intravenous injection of HCSS every 6
      hours in a dose of 5 mg hydrocortisone/kg would maintain hydrocortisone level at
      100 to 150 micrograms/dl. HCSS did not show a rapid improvement of the pulmonary
      functions, but showed a tendency to improve the functions over 4 hours.
      Subcutaneous injection of epinephrine after HCSS resulted in a significant
      improvement of pulmonary functions compared to those by epinephrine alone. We
      concluded that hydrocortisone showed a slowly evolving improvement of pulmonary
      function and increased the responsiveness to beta-agonists.

PMID- 8250720
TI  - [Relation of platelet activating factor induced airway hyperresponsiveness to
      thromboxane A2 and neutrophil in dogs].
AB  - We studied the relation of the airway hyperresponsiveness induced by platelet
      activating factor (PAF) inhalation to thromboxane (Tx)A2 and neutrophil in ten
      dogs. Airway responsiveness to inhaled methacholine was determined by Astograph
      (7 Hz oscillation method), PAF (1000 micrograms/ml) was delivered as an aerosol
      generated from a Devilbiss 646 nebulizer for ten minutes. After determination of
      airway responsiveness, we carried out bronchoalveolar lavage and measured the
      TxB2 levels and the number of neutrophils in bronchoalveolar lavage fluid (BALF).
      Airway responsiveness developed significantly (p < 0.01), and the levels of TxB2
      and the number of neutrophils in BALF were increased (p < 0.01) 3 hr after PAF
      inhalation. The change in airway responsiveness correlated significantly with the
      percent change of TxB2 levels (r = 0.746, p < 0.05). However no significant
      correlation was recognized between the increase in TxB2 levels and the increase
      in the number of neutrophils, nor between the change in airway responsiveness and
      the increase in the number of neutrophils. These results suggest that the
      increase in airway responsiveness induced by PAF inhalation is involved in the
      hyperproduction of TxA2 but that TxA2 is not released from neutrophils
      infiltrating into the airway; furthermore neutrophils may not induce airway
      hyperresponsiveness in dogs.

PMID- 8250721
TI  - [Airway inflammatory cell dynamics during late asthmatic reactions induced by
      toluene diisocyanate in guinea pigs. I. Bronchoalveolar lavage study].
AB  - We developed a guinea pig model of late asthmatic reactions (LAR) induced by
      toluene diisocyanate (TDI), and investigated airway inflammatory cell dynamics
      during LAR by bronchoalveolar lavage (BAL) in this model. The guinea pigs were
      sensitized by nasal application of 10% TDI solution once daily for 7 consecutive
      days. Thereafter, the animals were challenged with 5% TDI solution, in the same
      manner, on every 7th day for 4 to 11 times. Each guinea pig was pretreated with
      metyrapone before challenge. BAL was performed at each time point after the final
      challenge. The immediate asthmatic reaction and the LAR induced in the challenges
      were found to be 66% and 55%, respectively. A significant BAL fluid eosinophilia
      was observed in the guinea pigs during and after LAR (i.e., 3, 6, 24 and 168
      hours after challenge), in comparison to the animals without LAR and to the
      control animals only exposed to ethyl acetate, a solvent for TDI. The number of
      eosinophils peaked at 6 hours after challenge. However, no significant changes
      were observed in the numbers of macrophages, lymphocytes or neutrophils in BAL
      fluid during LAR. We conclude that eosinophils play an important role in LAR in
      this model. This model seems to be useful in investigating the pathophysiology of
      TDI-induced asthma.

PMID- 8250722
TI  - [Inhibition of eosinophil peroxidase release by chymotrypsin type protease
      inhibitors from activated human eosinophils].
AB  - Eosinophils contain many cytotoxic mediators including eosinophil peroxidase
      (EPO) in their granules and these mediators are released by various
      pathophysiological stimuli, resulting in severe damage to various epithelia.
      However, little is known about the intracellular mechanism of the degranulation.
      Here we report that eosinophils isolated from patients with bronchial asthma who
      were not taking corticosteroid hormone had significant amidolytic activities on
      Suc-Ala-Ala-Pro-Phe-MCA, and also that the activity was completely inhibited by
      chymostatin (1 x 10(-4) M), eglin C (1 x 10(-4) M), and peptide boronic acid (1 x
      10(-4) M), indicating that eosinophils contain a chymotrypsin-like serine
      protease in the fraction eluted in 50 mM potassium phosphate buffer, pH 8.0
      containing 2 M NaCl. Among the various types of protease inhibitors examined, one
      of the chymotrypsin-type proteases chymostatin (1 x 10(-4) M), but none of the
      other types of proteases such as leupeptin and E-64, markedly inhibited the EPO
      release (c.a. 60%) from eosinophils stimulated by immunoglobulin-G (2.5 mg
      protein/ml beads) in the presence of rhIL-5 (10 ng/ml) or platelet-activating
      factor (1 x 10(-7) M), although it had no effect on the release by calcium
      ionophore A23187 (1 x 10(-7) M).

PMID- 8250723
TI  - [Cross-allergenicity between rice and buckwheat antigens and immediate
      hypersensitive reactions induced by buckwheat ingestion].
AB  - Immediate hypersensitive reactions (IHR) induced by buckwheat ingestion are
      considered to be IgE-mediated. However we found 28 subjects without IHR to
      buckwheat ingestion out of 46 subjects who had positive RAST values for both
      buckwheat and rice antigens. The IHR-positive group showed significantly higher
      RAST values for buckwheat antigens (p < 0.01) but lower RAST values for rice
      antigens (p < 0.01) than did the IHR-negative group. RAST values for buckwheat
      and rice were significantly correlated with each other (p < 0.01) in the IHR
      negative group, but not in the IHR-positive group. An effective dose-dependent
      inhibition was obtained in a RAST inhibition assay between homologous
      combinations of inhibitor and disc antigens such as rice and rice or buckwheat
      and buckwheat. The IHR-positive group showed no significant RAST inhibition
      between heterogeneous combinations of rice and buckwheat antigens. In contrast,
      the IHR-negative group showed a significant decrease in IgE binding even in the
      RAST inhibition assay between heterogenous combinations. These results led to the
      conclusion that there is cross-reactivity with IgE antibodies between buckwheat
      and rice and that IgE antibodies from IHR-negative subjects might recognize the
      epitopes on buckwheat antigens which cross react with rice antigens, whereas IgE
      antibodies from IHR-positive subjects might bind to buckwheat-specific epitopes.

PMID- 8250724
TI  - [Experimental acute lung injury in guinea pigs after aerosol challenge with
      sonicated Pseudomonas aeruginosa whole cells].
AB  - Acute hemorrhagic alveolitis was elicited in the lungs of guinea pigs by aerosol
      challenge with sonicated P. aeruginosa whole cells. Histological findings showed
      the severe inflammatory changes, which were characterized by the inflammatory
      infiltration of alveolar macrophages (AM), polymorphonuclear leukocytes (PMN) and
      eosinophils in the peribronchial and the alveolar space at 8 hours after the
      challenge. A marked increase of PMN as well as AM was noted in the bronchial
      alveolar lavage fluid (BALF) at 8 hours after the challenge and the increase of
      the numbers of AM and PMN in the BALF remained until 24 hours after challenge.
      The complement titer (CH50) and C3 component in the serum decreased at the early
      stage, and CH50 maintained low level and C3 component increased gradually.
      Polyethyleneglycol precipitation-complement consumption test (PEG-CC) of the BALF
      showed the existence of immune complexes formed in the airway after aerosol
      inhalation. These data suggest that the immune complexes of P. aeruginosa
      activate the complement system in the lungs, which is followed by the
      infiltration of inflammatory cells. Guinea pigs which were pretreated with cobra
      venom factor significantly reduced the extent of the inflammatory changes in the
      lungs. The results suggests that the complement system might act as an important
      factor of the acute lung injury in this model.

PMID- 8250725
TI  - [Effect of intracerebral injections of tumor necrosis factor and interleukin-1].
AB  - In order to examine the effect of cytokines on the central nervous system, we
      injected tumor necrosis factor (TNF) alpha or interleukin-1 (IL-1) alpha into the
      brains of mice. Although mice injected with saline alone exhibited no
      inflammatory responses, histopathological studies of mice injected with TNF alpha
      or IL-1 alpha revealed mild mononuclear cell infiltration around the blood
      vessels, edema and mild hemorrhage several millimeters distant from the needle
      track. These findings are similar in pattern to those observed in the early stage
      of experimental allergic encephalomyelitis (EAE). Increased vascular permeability
      induced by injections of TNF or IL-1 may play a role in the pathogenesis of these
      inflammatory responses. The direct cytokine injection model offers a new way of
      examining the mechanisms of early inflammation in the central nervous system.

PMID- 8250726
TI  - [The allergic reaction to acid protease released by Candida albicans].
AB  - The species of Candida albicans (C. albicans) are known to colonize mucocutaneous
      regions as part of the endogenous flora. C. albicans is also known as an
      important allergen in human allergic diseases. However, the major allergen of C.
      albicans has not been identified yet. Acid protease released from C. albicans
      (CAAP) cleaves IgA or the secretory component to enable C. albicans to colonize
      on the mucous membrane. In this study, using CAAP and crude Candida antigen as
      challenging antigens, we carried out conjunctival provocation tests (CPT) on 68
      adult bronchial asthmatic patients who showed immediate positive skin reactions
      to crude Candida antigen. In several patients we performed serum IgE antibody
      (RAST), histamine release from peripheral leukocytes (HRT) and bronchial
      provocation tests (BPT) to CAAP. Six of the 8 patients who showed positive CPT to
      crude Candida antigen (75%) showed positive CPT responses to CAAP. On the other
      hand, only 1 of the 59 patients who showed negative CPT to crude Candida antigen
      (1.7%) showed positive CPT reactions to CAAP. Two female patients showed positive
      RAST and HRT to both crude Candida and CAAP. They also showed positive CPT and
      BPT. One patient had positive RAST results but negative HRT, CPT and BPT results.
      These results show that CAAP is an important allergen for atopic patients
      allergic to C. albicans.

PMID- 8250727
TI  - [Effect of nitroprusside on gap junctions of single tracheal smooth muscle cells
      excised from rats].
AB  - To investigate the effect of nitroprusside on gap junctions of tracheal smooth
      muscle cells, we ionophoretically injected sodium nitroprusside into single
      tracheal smooth muscle cells excised from rats. The input resistance of the
      tracheal smooth muscle cells increased after the injection of nitroprusside. This
      results suggests that nitroprusside blocks gap junctions of tracheal smooth
      muscle cells.

PMID- 8250728
TI  - [Immune mechanism of allergy].

PMID- 8250729
TI  - [Distribution of MCT and MCTC in nasal mucosae--relationship with formalin
      sensitive mast cells and formalin-resistant mast cells].
AB  - The distributions of tryptase-positive, chymase-negative mast cells (MCT) and
      tryptase-positive, chymase-positive mast cells (MCTC) were examined in allergic
      and non-allergic nasal mucosae. Sequential double immunohistochemical staining
      with anti-chymase and anti-tryptase antibodies was carried out. Additionally,
      metachromatic cells were examined in formalin or Carnoy-fixed tissues. The main
      types of mast cells in the epithelium were MCT and formalin-sensitive mast cells
      (FSMC) and those in the lamina propria were MCTC and formalin-resistant mast
      cells (FRMC) in both allergic and non-allergic nasal mucosae. The densities of
      MCT and FSMC in the nasal epithelium were observed to be significantly higher in
      the allergic group than in the non-allergic group. The distributions of MCT and
      FSMC, MCTC and FRMC tended to be similar in the nasal mucosa. The
      immunohistochemical method offered some advantages such as a higher sensitivity
      and the possibility to make observations in one section. Recently, human mast
      cells have been classified as either MCT or MCTC. It seems that information of
      the distribution of MCT and MCTC and of FSMC and FRMC is useful in studying the
      organ specificity and functional heterogeneity of mast cells in allergic tissues
      such as those found in nasal allergy.

PMID- 8250730
TI  - [Assessment of the amount of drug deposited in the lungs of asthmatic children
      using disodium cromoglycate as the marker].
AB  - Disodium cromoglycate (DSCG) is easily absorbed from the airways and lungs, and
      is excreted unchanged in the urine and bile. Therefore it is possible to estimate
      the dose of DSCG deposited in the airways and lungs based upon urinary excretion.
      The urinary concentration of DSCG was measured by the HPLC method in 78 asthmatic
      children aged 0 to 16 years after they had inhaled 20 mg nebulizer solutions with
      facemasks. Jet-type nebulizers were used. The mean urinary excretion of DSCG in
      the patients aged 0, 1, 2 and 3 years from 4-hour urinary collection represented
      0.204%, 0.231%, 0.593%, 0.790%, respectively, of the dose administered. In the
      patients aged 3, 4, 5-6, 7-9 and 10-16 years, from 24-hour urinary collection,
      the figures were 0.625%, 0.895, 0.855, 1.176%, 1.070%, respectively. The mean
      dose deposited in the airways and lungs of the age groups 0-1, 2, 3, 4-6, 7-9,
      and 10-16 years represented approximately 0.5%, 1.4%, 1.4-1.8%, 2.0%, 2.7%, 2.4%,
      respectively, of the dose administered. Although there was a wide range in the
      total amount of DSCG deposited in the airways and lungs of asthmatic children,
      these data seem to provide a useful guide to standardizing the dosing in
      inhalation therapy.

PMID- 8250731
TI  - [Serum levels of soluble CD25 (soluble interleukin 2 receptor) in asthmatic
      patients].
AB  - Serum sCD25 levels were measured in 64 asthmatic patients and 22 healthy subjects
      by enzyme-liked immunosorbent assay. Serum sCD25 levels in the asthmatic patients
      were significantly higher than those in the healthy subjects (p < 0.02). Serum
      sCD25 levels in the asthmatic patients during attack were slightly higher than in
      those in remission, but there was no significant difference between the two
      groups. We studied changes of serum sCD25 level in 13 asthmatic patients in
      remission and during attack and found that serum sCD25 levels were significantly
      higher during attack than in remission (p < 0.02). Serum sCD25 levels in the
      asthmatic patients undergoing steroid therapy were significantly lower than in
      those who were not (p < 0.05). The significance of serum sCD25 in bronchial
      asthma still remains unclear, but these results suggest that T cells play an
      important role in bronchial asthma.

PMID- 8250732
TI  - [Effects of a cyclic nucleotide phosphodiesterase isoenzyme type III inhibitor,
      SDZ MKS 492 on airway responsiveness in beagles].
AB  - To elucidate the effects of cyclic nucleotide phosphodiesterase (PDE) isoenzyme
      inhibition on airway responsiveness, we studied the effects of a selective PDE
      isoenzyme type III inhibitor, SDZ MKS 492, on airway responsiveness to inhaled
      methacholine (Mch) in 6 beagles. Base-line respiratory resistance and airway
      responsiveness to Mch were determined by modified Astograph (7 Hz oscillation
      method). SDZ MKS 492 (1.0 mg/kg, 0.3 mg/kg or 0.1 mg/kg) was orally administered
      1 hr prior to the determination of airway responsiveness at intervals of one
      week. Base-line respiratory resistance was decreased in a dose-dependent manner
      by SDZ MKS 492. SDZ MKS 492 significantly decreased airway responsiveness to Mch
      (log D min) in a dose-dependent manner, and the airway responsiveness (log PD2.0
      Mch) was significantly decreased by 1.0 mg/kg of SDZ MKS 492. These results
      indicate that selective inhibition of PDE isoenzyme type III results in a
      decrease in respiratory resistance and airway responsiveness.

PMID- 8250733
TI  - [Detection of interleukin-6 in serum and cerebrospinal fluid of patients with
      neuroimmunological diseases].
AB  - We quantitatively measured interleukin-6 (IL-6) levels in sera and cerebrospinal
      fluids (CSF) of patients with neuroimmunological diseases. Measurements were
      carried out by enzyme linked immunosorbent assay (ELISA) with anti-human IL-6
      monoclonal antibody. The upper limit of IL-6 levels in the sera of normal
      controls was 15 pg/ml. Significant elevations of IL-6 levels were observed in the
      sera of patients with multiple sclerosis (MS) (212 +/- 320 pg/ml), Guillain-Barre
      syndrome (GBS) (90 +/- 62 pg/ml), myasthenia gravis (41 +/- 22 pg/ml), and
      polymyositis (119 +/- 72 pg/ml), when compared to those of controls (p < 0.05).
      The upper limit of IL-6 levels in the CSF of normal controls was 6.5 pg/ml. A
      significant elevation of IL-6 levels was observed in the CSF of patients with MS
      (131 +/- 307 pg/ml) (p < 0.05). However, no significant elevation of IL-6 levels
      was observed in the CSF of patients with GBS. The correlation indexes between CSF
      IL-6 and cell count, total protein levels, IgG levels in the CSF of MS patients
      were 0.776 (p < 0.001), 0.769 (p < 0.001) and 0.759 (p < 0.001), respectively.
      Serum IL-6 was not correlated with CSF IL-6 in MS patients. The elevated levels
      of IL-6 in the patients with these neuroimmunological diseases suggest that B
      cells may be polyclonally activated in the sera of patients with these
      disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250734
TI  - [Clinicopathological significance of immune complex (IC) along the tubular
      basement membrane (TBM) in lupus nephritis].
AB  - This paper reports on the clinicopathological significance of IC along the TBM in
      lupus nephritis. Renal biopsies were performed on 60 patients with SLE. All of
      the patients demonstrated immunoglobulin deposits in the glomeruli, and 16 of
      them also showed immune deposits along the TBM. The IgG in the glomeruli or along
      the TBM completely disappeared after incubation with human IgG, IgG Fc fragments,
      but not with human F(ab')2, rabbit or rat IgG. These results suggest that IgG
      along the TBM are similar in nature to IC in the glomeruli and that the IC are
      composed of IgG rheumatoid factor. The square of tubulointerstitial lesions was
      more severe in the group with IgG along the TBM than in the group with no IgG
      along the TBM (5.85 +/- 9.88% vs 1.29 +/- 3.72%). In addition of this, the group
      with IgG deposits along the TBM frequently demonstrated type IV lupus nephritis.
      Although the renal function was not significantly different in the both groups,
      the serum complement level was lower in the cases with IC deposits in the TBM.
      From these results, it is suggested that IC deposits along the TBM as one of the
      important inflammatory agents lead to the severe forms of tubulointerstitial
      injury and show the active stage of the disease in SLE patients.

PMID- 8250735
TI  - [Possible presence of protein kinase in human peripheral blood eosinophils].
AB  - Peripheral blood eosinophils from normal subjects and patients with atopic
      dermatitis were isolated on a Percoll gradient and incubated with [gamma 32P] ATP
      in the presence of Mg2+. After the reaction was stopped, SDS/PAGE was performed
      and autoradiography was used to determine the incorporation of 32P into the
      proteins in the eosinophils. Both normodense and hypodense eosinophils showed 32P
      incorporation into the proteins at the molecular weights of 65 kDa & 66.2 kDa.
      These reactions were dependent upon Mg2+ concentration, and maximal response was
      observed at concentrations of 2-6 mM MgCl2. 32P incorporation into the bands was
      dependent upon the reaction time and temperature, and maximal response was
      observed at 20 degrees C. 32P incorporation into the proteins was inhibited by
      Ca2+ in a dose-dependent manner. Cyclic GMP at concentrations of 5 x 10(-8) to 5
      x 10(-6) M enhanced the 32P incorporation. These data suggest the possible
      presence of protein kinase in human peripheral blood eosinophils.

PMID- 8250736
TI  - [Adhesion ultrastructures of mononuclear cells in experimentally-induced
      silicotic granuloma].
AB  - Experimental silicosis was induced by intratracheal infusions of 1 ml saline
      containing 50 mg standard silica (less than 5 microns diameter) in Sprague-Dawley
      rats. The lung tissues were observed histologically and ultrastructurally from
      half an hour up to 4 months. Macrophages, neutrophils, desquamated cells and
      their debris piled up around the alveolar ducts where the central cores of
      silicotic granuloma appeared. The granuloma became apparent by day 4 after the
      infusion and were covered by type II alveolar epithelial cells and bronchiolar
      cuboidal epithelial cells. Macrophages, fibroblasts and epithelial cells began to
      react to the antibody against proliferating cell nuclear antigen (PCNA)
      indicating self-replication on day 1. Macrophages in the granuloma made a close
      interdigitation with adjacent macrophages, and they gradually formed
      subplasmalemmal linear densities (SPLD) as paired forms between adjacent plasma
      membranes, and unpaired forms facing the interstitial matrix. SPLD were composed
      of linear densities with actin-like microfilaments along the leaflets of plasma
      membrane and were associated with extracellular dense bands which resembled a
      limited length of basement membrane. Interdigitation and SPLD structures were
      quite rare on day 1, but the number of macrophages with both structures
      increasingly appeared. The frequency of SPLD in macrophages also increased on a
      time course of granuloma maturation up to 4 months. Thus SPLD, which were
      originally found in the mononuclear phagocytes including macrophages, epithelioid
      cells and multi-nucleated giant cells, particularly in immune granuloma of man,
      also played a basic role in immobilizing macrophages in lesions of silica-induced
      granulomas.

PMID- 8250737
TI  - Cardiovascular effects of low and high doses of clonidine in rats.
AB  - Clonidine was a partial agonist of adrenoceptors and the effects of a range of
      clonidine doses on the mean arterial pressure and heart rate of rats were
      evaluated. It was found that low doses of clonidine, 30-300 micrograms/kg,
      induced a significant hypotension whereas high doses of clonidine, 3-18 mg/kg,
      were unable to decrease the blood pressure significantly. The reversal by high
      doses of clonidine of the hypotension induced by low dose of clonidine was
      possibly due to the blood vessel contraction induced by a high dose of clonidine.
      On the other hand, both low and high doses of clonidine induced bradycardia in
      the in vivo as well as in vitro studies.

PMID- 8250738
TI  - Lipid peroxide levels in type II hyperlipoproteinemic subjects.
AB  - The purpose of this study was to evaluate, under the most rigorous precautionary
      measures against in vitro oxidation, whether the baseline lipid peroxide levels
      in hypercholesterolemic subjects were higher than those in normolipidemic
      subjects. Two methods were employed: thiobarbituric acid (TBA), and hemoglobin
      methylene blue (HbMB). Blood was collected into EDTA tube and centrifuged at 4
      degrees C for 30 min to collect plasma, then protected from in vitro oxidation
      with preservatives and N2. Serum was from blood samples allowed to clot at 20
      degrees C for 1 h, then protected from oxidation. Determination of lipid peroxide
      was carried out within 2 h of blood collection. Results from 35
      hypercholesterolemic and 34 control subjects showed that lipid peroxide levels
      obtained from both methods were significantly higher in serum than in plasma for
      both groups, suggesting a greater rate of lipid peroxidation occurred in serum
      during clot formation. However, no significant difference in lipid peroxide
      levels was found between patients and controls in either serum or plasma by
      either assay method. No correlation existed between lipid peroxide values and
      plasma cholesterol or LDL-cholesterol levels. These results suggest that the
      mechanism for a higher tendency towards atherosclerosis in hypercholesterolemic
      subjects is not related to baseline levels of plasma lipid peroxide.

PMID- 8250740
TI  - Transcranial Doppler evaluation of cerebrovascular reactivity to acetazolamide in
      normal subjects.
AB  - Acetazolamide (AZ), the selective inhibitor of carbonic anhydrase, was proved by
      intravenous Xenon 133 technique to increase cerebral blood flow (CBF). In this
      study cerebrovascular reactivity to AZ was evaluated in 10 normal subjects by
      transcranial Doppler (TCD) within the middle cerebral artery (MCA), since several
      reports have demonstrated that velocity of cerebral blood flow is well correlated
      to CBF. After 1 gr AZ injection blood flow velocity markedly increased in all
      subjects, with a peak in both systolic and diastolic velocity 20 min after drug
      administration. At that time systolic velocity increased by 35% and diastolic
      velocity by 50% in comparison to basal values. In contrast with Xenon 133
      technique which gives one measurement only for each investigation, TCD allows a
      continuous monitoring of haemodynamic change following AZ infusion. MCA diastolic
      velocity at rest was inversely related to age (r = -.804, p < 0.01); baseline
      diastolic velocity was inversely related to the maximum percentage increment (r =
      -.745 p < .05). No change in blood pressure and heart rate was observed under
      experimental conditions. These results, confirm the usefulness of the AZ test in
      the evaluation of cerebrovascular reactivity and strongly support the use of TCD
      technique applied to AZ in order to investigate cerebrovascular haemodynamics in
      normal healthy subjects and in patients at risk of cerebrovascular insufficiency.

PMID- 8250739
TI  - Differences in LDL receptor-mediated metabolism of three low density lipoprotein
      subfractions by human monocyte-derived macrophages: impact on the risk for
      atherosclerosis.
AB  - The metabolism of three low density lipoprotein (LDL) subfractions by human
      monocyte-derived macrophages (HMDM) through the LDL receptor pathway was studied.
      The three LDL subfractions, very light LDL1, light LDL2 and heavy LDL3, were
      isolated from serum pools of normolipidemic subjects by density gradient
      ultracentrifugation. The LDL subfractions were shown to differ in molecular size
      and chemical composition but not in electrophoretic mobility on agarose gel. Cell
      specific association, cell specific degradation and stimulation of cholesteryl
      esterification were determined in parallel after incubation of HMDM with
      increasing amounts of LDL-protein of the three LDL subfractions. The experiments
      were repeated four times with freshly prepared LDL subfractions. Both the cell
      specific association and degradation increased more with increasing LDL-protein
      concentration for LDL1 than for LDL3 (p < 0.001). The results for LDL2 were
      intermediate between those for LDL1 and LDL3 and differed significantly from both
      (p < 0.05). For the stimulation of cholesteryl ester formation, the curves for
      LDL1 and LDL2 increased more with increasing LDL-protein concentration than that
      for LDL3 (p < 0.001); the results for LDL1 and LDL2 did not differ significantly
      from each other. These differences between LDL subfractions in cholesteryl
      esterification were independent of the cholesterol content of the LDL
      subfractions. The results show that LDL subfractions have different rates of LDL
      receptor-mediated catabolism by HMDM. As HMDM play an important role in the
      formation of atherosclerotic plaques, the differences between the LDL
      subfractions in catabolism by HMDM, may result in differences in atherogenicity
      between LDL subfractions isolated from normolipidemic subjects.

PMID- 8250741
TI  - [The enigma of ischemia without pain].

PMID- 8250742
TI  - [Biplane transesophageal echocardiography. Experience with 130 outpatients].
AB  - PURPOSE: To analyse the utility of transesophageal echocardiography (TEE) as a
      complementary technique to transthoracic echocardiographic (TTE) comparing
      results and additional informations. METHODS: One hundred and thirty consecutive
      outpatients (66 male) submitted to TEE, with age ranging from 12 to 84 years were
      studied. Patients were grouped according to the main indication: evaluation of
      prosthetic valves, 21 patients; cardiac source of emboli, 43; diseases of the
      aorta, 17; infective endocarditis, 14; congenital heart diseases, 14 and other
      abnormalities in 21 patients. RESULTS: TEE provided additional and important
      information in all groups. Perivalvular leakage was observed in 42.1% of patients
      with prosthetic valves. Vegetations were detected in 45.5% of the suspected cases
      of endocarditis (missed by TTE). Dissection of aorta was diagnosed in 35.2% of
      patients with suspected disease and atrial septal defect was successfully
      recognized in 80% of the cases. No complications were observed. CONCLUSION: TEE
      is a safe and usefull complementary non-invasive diagnostic tool in the
      assessment of structures such as left atrium, left atrial appendage, thoracic
      aorta, prosthetic valves and in the investigation of infective endocarditis.

PMID- 8250743
TI  - [Segmental changes in contractility of the left heart ventricle in Chagas
      cardiomyopathy with and without ventricular dilatation].
AB  - PURPOSE: To evaluate left ventricular (LV) segmental wall motion abnormalities in
      dilated and nondilated chronic chagasic myocarditis (CCM), to better understand
      the myocardial dysfunction progression in this pathology. METHODS: Sixty nine
      patients with the CCM, 39 had normal end-diastolic left ventricular dimension
      (LVEDD) and normal cardio-thoracic ratio (CTR) (group A), and 30 had increased
      LVEDD and CTR (group B), all of them with abnormal EKG, had the LV global and
      segmental contractility analysed by two-dimensional echocardiogram (Echo). A
      point score system to the LV contractility was applied. RESULTS: Segmental wall
      motion abnormalities were seen in 68% of the patients: apical 64%, postero
      inferior 30%, septal 17%, anterior 6% and lateral 0. Apical aneurysm was observed
      in 42% of the patients, postero-inferior in 6% and basal septal in 3%. There was
      a statistically significant correlation between the LVDD and the LV score of
      contractility (r = 0.66; p = 0.0000). The LV contractility was normal in 28% of
      the patients, 47% in group A and 3% in group B. While in group A the abnormal
      pattern of contractility was segmental in all, but one patient, in group B it was
      diffuse in the large majority (93%). CONCLUSION: Initially LV abnormality in CCM
      is segmental. Beyond the apex, other regions of the LV are involved, the postero
      inferior wall and basal septum for instance, even with aneurysm morphology. The
      CCM seems to evolve from an stage with essentially segmental wall motion
      abnormalities and normal LVDD to LV dilatation and diffuse hypocontractility.

PMID- 8250744
TI  - [Diagnosis and therapeutic follow-up of patients with massive pulmonary emboli by
      two-dimensional echocardiography].
AB  - PURPOSE: The aim of the study was to analyse the role of 2D echocardiogram (ECHO)
      in the diagnosis of massive pulmonary embolism (PE), and in the follow-up after
      fibrinolytic or surgical treatment. METHODS: Echocardiographic studies were
      retrospectively analysed in seven patients, 5 male, mean age 37 +/- 19 years,
      with massive pulmonary embolism (PE) confirmed by pulmonary angiography. Six of
      them were submitted to fibrinolytic therapy with IV streptokinase (SK), and one
      underwent surgery. The diagnosis of PE by ECHO was made by the detection of
      thrombi in the pulmonary vascular bed. ECHO measurements included the right
      ventricular diastolic diameter (RVDD), interventricular septal motion (IVS),
      acceleration time (AcT), and peak pulmonary artery pressure (PAP). RESULTS: The
      ECHO study diagnosed thrombi in five out of seven patients (71%), mainly if they
      were present in the right main pulmonary artery (four cases -80%). It was also
      able to locate one out of five patients with thrombus in the right lobar artery
      and one out of two patients in the left main pulmonary artery; it was unable to
      identify six patients with involvement of the left lobar arteries. Four out of
      five patients with PE, diagnosed by ECHO, were submitted to fibrinolytic therapy,
      and one underwent surgery. The follow-up study showed dissolution of the thrombus
      in three of those with SK and in the one with surgical treatment. The initial
      ECHO study showed five out of 7 patients with increased RVDD, 5/7 patients with
      abnormal IVS motion, and all of them with decreased AcT (64 +/- 16 ms). The PSP
      was 64.4 +/- 22.8 mmHg by ECHO, versus 75.4 +/- 24.03 mmHg by angiography (r =
      0.78; p = 0.11). There was a reduction of the RVDD (30 +/- 5.02 to 23 +/- 2.2)
      and an increased of the AcT (50 +/- 10.8 to 106.67 +/- 16) at the serial
      examination. CONCLUSION: The ECHO study is an important tool for the diagnosis of
      PE, informing about pulmonary pressure, presence and position of thrombus, and
      treatment results.

PMID- 8250745
TI  - [Preoperative cardiological evaluation. Report of 255 cases].
AB  - PURPOSE: To study preoperative cardiological consultations in a cardiology
      referral center in a general hospital. METHODS: Two hundred and fifty five
      patients were studied between June and December 1989; the ages ranged between 16
      and 82 (mean 55) years, 120 (47%) were male and 135 (53%) female. A questionnaire
      was applied by the physicians during consultation. RESULTS: Main symptoms were
      thoracic pain in 30 (11.8%) cases, dyspnea in 57 (22.4%), palpitations in 13
      (5.1%). Symptoms of cardiac disease were absent in 141 (55.3%) patients. On
      physical examination arterial hypertension was detected in 75 (29.4%) cases and a
      cardiac murmur in 21 (8.2%). Diagnosis of coronary artery disease was made in 30
      (11.8%) cases--13 (5.1%) with history of previous myocardial infarction, aortic
      valve stenosis in 5 (1.9%), other valvular heart diseases in 14 (5.5%), cardiac
      arrhythmias in 11 (4.3%). Heart disease was absent in 90 (35.4%) patients. Sixty
      five (25.5%) patients were on drug therapy for heart diseases. Consultations were
      obtained for patients that had been already admitted to the hospital in 171 (67%)
      cases. Cardiological follow up was recommended to 150 (58.8%) patients. Seven
      patients died; the cause of the death was related to the primary disease.
      Contraindication for surgery imposed by cardiological evaluation did not occur.
      CONCLUSION: In this study, patients with heart disease tolerated the surgical
      procedures. Preoperative cardiological evaluation added useful data for
      postoperative care and also for long term follow-up of the patients.

PMID- 8250746
TI  - [Percutaneous retrieval of intravascular foreign bodies].
AB  - PURPOSE: To report our experience on percutaneous vascular foreign body retrieval
      and to analyse current techniques employed. METHODS: From 1985 to 1991, 15
      (0.18%) of 7,963 procedures performed in the Cardiac Catheterization Laboratory
      Hospital Sao Paulo were intravascular foreign body retrieval: 9 (60%) intracath,
      4 (26.8%) diagnostic catheters, one Swan Ganz catheter entrapped at superior cava
      vein and one fragment of angioplasty guide-wire in the circumflex branch of the
      left coronary artery. The snare technique was used in 11 cases, a endomyocardial
      bioptome device in 1 case and modified snare technique for the intracoronary wire
      fragment retrieval was used in 1 case. In two cases of embolized fragment in
      peripheral arteries, no attempt was done for retrieval. RESULTS: All (100%) of
      the 13 attempted procedures were successful. The two foreign bodies not removed
      had an uneventful follow-up. CONCLUSION: The snare technique for percutaneous
      retrieval of intravascular foreign bodies is safe and has excellent results. The
      management peripheral fragments is not well defined yet.

PMID- 8250747
TI  - [Reinfarction after thrombolytic therapy. Results obtained with readministration
      of thrombolytic agent in 3 patients].
AB  - From 1985 to 1990, 120 patients within 6h after the onset of acute myocardial
      infarction were submitted to thrombolytic treatment. In 4 patients, there were
      clinical and electrocardiographic (ECG) changes of reinfarction. Three of them
      were undergone to a second thrombolytic therapy with streptokinase (SK). Two had
      infarction of the inferior wall, and one on the anterior wall. The patients were
      managed with the same SK dosage as in the first episode and the same protocol of
      infusion. All 3 patients, after new SK infusion showed evidence of myocardial
      reperfusion with relief of pain and improvement of the ECG. One patient, 24h
      after retreatment, had another reinfarction treated with emergency angioplasty of
      the right coronary artery, which was totally occluded. One patient (case n. 2),
      presented haematoma of right arm after punction of the subclavian vein and the
      other two patients did not show any serious intecorrence related to the new
      thrombolytic treatment. All of them were found alive over one year of follow-up.

PMID- 8250748
TI  - [High-resolution electrocardiogram in the study of early rejection of heart
      transplant by spectral temporal mapping].
AB  - At the present time there is great interest in seeking non invasive methods for
      reduction and precise orientation of the endomyocardial biopsy after heart
      transplant. Two cases of orthotopic heart transplant followed by spectro temporal
      mapping of signal averaging electrocardiography and integral calculation are
      reported. The results that identified the rejection process are presented and
      several aspects of this method are discussed.

PMID- 8250749
TI  - [An unusual indication of deep hypothermia with total circulatory arrest for
      myocardial revascularization surgery].
AB  - The authors relate a case of 69 years old patient with unstable angina and left
      main coronary artery disease, who underwent aggressive mediastinal radiotherapy
      for lymphoproliferative syndrome 20 years ago and who needed urgent myocardial
      revascularization. Due to great calcification and heavily heart adherences it was
      performed 20 degrees C deep hypothermic circulatory arrest to avoid aortic
      clamping and to make the anastomosis with better exposition of the aorta and
      coronary arteries.

PMID- 8250750
TI  - [Nonsurgical treatment of coronary pulmonary arteriovenous fistula].
AB  - Fifty eight year old man, with dyspnea, fatigue and progressive angina underwent
      cinecoronarography, which showed an arterio-venous coronary-pulmonary fistula
      originating from the circumflex artery to the pulmonary circulation. We decided
      to occlude it percutaneously, using a detachable balloon technic. The occlusion
      was accomplished successfully. Clinical evolution was excellent and the follow-up
      cinecoronarography 6 months later showed the maintainance of the initial results.

PMID- 8250751
TI  - [Aortic coarctation associated with a large aneurysm].
AB  - The case of a symptomatic 16-year-old girl, referred with the diagnosis of
      coarctation of the aorta is presented. Aortography showed a severe coarctation
      and a huge aneurysm distal to the coarctation. Successful operation was performed
      with resection of the coarctation and aneurysm and interposition of a tube of
      bovine pericardium for the anastomosis. Two months after the operation the blood
      pressure was normal and a 10 mm/Hg gradient was detected by doppler
      echocardiography.

PMID- 8250752
TI  - [Postpericardiotomy syndrome. 4 decades of etiological doubt].

PMID- 8250753
TI  - [Fosinopril in a daily single dose in mild and moderate hypertension. Brazilian
      multicenter study].
AB  - PURPOSE: To evaluate during 12 weeks the effectiveness and safety of once-a-day
      fosinopril (10 or 20 mg/day comparative to placebo) in mild to moderate
      hypertensives according to an open design comparative to placebo. METHODS: One
      hundred and nineteen patients were studied; 52 +/- 11 years (mean +/- sd) range
      18 a 76 years, 86 women and 33 men, 57% whites, 26% blacks and 17% mulattos, 71
      mild hypertensives (95 < or = diastolic pressure < or = 104mmHg) e 48 moderate
      hypertensives (101 < diastolic pressure < or = 115mmHg). RESULTS: There was a
      significant reduction in systolic/diastolic pressure on the 6th week of treatment
      (from 161 +/- 16/103 +/- 7 before to 148 +/- 16/94 +/- 9mmHg on the 6th week). On
      the 12th week of treatment there was an additional significant reduction in
      systolic/diastolic pressure (from 148 +/- 16/94 +/- 9 on the 6th week to 145 +/-
      17/89 +/- 8mmHg on the 12th week). There was a "favorable" response in 71% of the
      patients on the 12th week; 62% showed diastolic pressure < or = 90mmHg and 9%
      presented diastolic reduction > or = 10mmHg. There was no difference in the
      normalization rates between whites and non-whites, mild and moderate
      hypertensive, obese and non-obese patients, under or above 50 years of age and
      those patients from no drug-treatment to those on 3 drug before the study. There
      was no clinically relevant changes in laboratory evaluations before and at the
      end of the study. The number of adverse reactions was reduced in comparison with
      previous treatment. CONCLUSION: Fosinopril, according to our and others data, is
      effective and safe for the treatment of mild to moderate hypertensives, in whites
      or non-whites, obese or non-obese, younger or older than 50 years and receiving 0
      or 3 drugs before the study.

PMID- 8250754
TI  - Endometriosis and social class: an Asian experience.
AB  - The social class distribution in 147 patients confirmed to have endometriosis at
      laparoscopy was done to see if the disease was associated with affluence. Two
      hundred and eighty-one patients confirmed not to have endometriosis was used as
      controls. The patients were derived from a background population for which the
      social class characteristics was known. Endometriosis was significantly (p <
      0.001) associated with social class 1 and 2. However there was no association
      between social class distribution and the severity of the disease developed.

PMID- 8250755
TI  - Evaluation of sperm fertilizing capacity using the determination of acrosome
      reaction.
AB  - To evaluate the usefulness of the determination of acrosome reaction (AR) at 2
      and 4 hours of incubation for predicting sperm fertilizing capacity in vitro,
      semen samples obtained from 45 partners of couples participating in the IVF (in
      vitro fertilization) program were examined. The population was divided into 2
      groups, depending on the fertilization rate in the IVF program: Group A, with a
      good fertilizing capacity (> or = 50% fertilized oocytes); and Group B, with a
      poor fertilizing capacity (< 50% fertilized oocytes). The rate of acrosome
      reaction (%AR) was examined using the fluorescein isothiocyanate-conjugated
      Concanavalin A lectin method. The efficacy of this procedure was compared with
      that of the zona-free hamster oocyte human sperm penetration assay (SPA) and
      sperm characteristics (SC) that appear in routine semen analysis. The
      sensitivities in the test of AR, SPA and SC were 91%, 86% and 82%, respectively.
      However, their specificities were 83%, 48% and 43%, respectively. Therefore, the
      screening procedure using the determination of acrosome reaction might be a
      useful tool in predicting IVF results.

PMID- 8250756
TI  - Contraceptive practice before female sterilization.
AB  - The reproductive profile and contraceptive practice of 402 women undergoing
      female sterilization at the Central Women's Hospital are presented. Most (89%) of
      the interviewees were urban-dwellers and housewives with primary school
      education. Fifty-two percent were between 30 and 34 years with a mean of 4.2
      living children. Sixty-nine percent were past contraceptive users, of them; 29.9%
      had used more than one method. A considerable gap between knowledge and practice
      of different methods was found. Education level and employment had a significant
      effect on contraceptive practice (p < 0.01 and p < 0.5). The majority knew and
      used combined oral contraceptive pills and injectable progestogens, whereas
      rhythm, withdrawal and barrier contraception were lesser known methods.
      Contraceptive use was primarily for child-spacing whereas the main reasons for
      female sterilization were socioeconomic and achievement of desired family size.

PMID- 8250757
TI  - Postpartum hemorrhage producing acute ischemic optic neuropathy.
AB  - A rare case of bilateral peripartum blindness due to acute ischemic optic
      neuropathy (AION) occurring after an episode of postpartum hemorrhage is
      described. Massive blood loss and the resultant hypotension was instrumental in
      reducing the perfusion pressure at the optic nerve head and producing ischemic
      damage to it.

PMID- 8250758
TI  - Case report: spontaneous pregnancy following thymectomy for myasthenia gravis
      associated with premature ovarian failure.
AB  - We report the case of a 29-year-old woman who was diagnosed to have premature
      ovarian failure (POF) and myasthenia gravis at the age of 27 years. She was
      treated by thymectomy and pyridostigmine. Hormone replacement was started after
      the operation and she subsequently conceived spontaneously. We believe this is
      the first report of a spontaneous pregnancy after the diagnosis of POF associated
      with myasthenia gravis.

PMID- 8250759
TI  - Diagnostic problems relating to uterine cervical polyps with malignancy.
AB  - In order to clarify the diagnostic problems relating to, and the proper treatment
      of, uterine cervical polyps, 951 polyps were analyzed clinicopathologically. All
      polyps were examined histopathologically and divided into 2 groups: benign polyps
      (Group-1), and polyps with neoplastic or malignant lesions (Group-2). Polyp size
      and cervical cytology are not always reliable for predicting the correct
      diagnosis of neoplastic or malignant lesions. Colposcopic diagnostic accuracy was
      56.3%, but increased to 75.0% when combined with cytology. Neoplastic or
      malignant lesions were found at both the cervical polyp and the cervix in 21 out
      of 24 Group-2 patients (87.5%). These results suggest that in order not to miss
      rare neoplastic or malignant lesions in polyps and/or cervices, histopathological
      examinations of all polyps, aided by cervical cytology and colposcopic
      observation, are necessary.

PMID- 8250760
TI  - Neoadjuvant chemotherapy using a platinum, vincristine and peplomycin (CVP)
      combination in patients with carcinoma of the uterine cervix.
AB  - Neoadjuvant chemotherapy consisting of a cis-platinum, vincristine and peplomycin
      (CVP) combination has been used to treat patients with carcinoma of the uterine
      cervix at our departments since 1983. Twenty-one patients are reviewed in this
      study. A high response rate (71.4%) was obtained with 19.0% complete and 52.4%
      partial responses prior to radical therapy. Survival times and the progression
      free interval for stage I and III disease treated with CVP show improvement
      compared to patients not treated with CVP. No life-threatening toxicity related
      to chemotherapy was noted. This combination chemotherapy used in neoadjuvant
      setting warrants further study.

PMID- 8250761
TI  - Color and pulsed Doppler ultrasonography of reversed umbilical blood flow in an
      acardiac twin.
AB  - Prenatal diagnosis of an acardiac twin pregnancy was performed. At 30 gestational
      weeks, pulsed color Doppler ultrasound revealed polyhydramnios, reversed
      pulsatile blood flow in the umbilical artery and vein of the acardiac twin, and
      artery-artery anastomosis on the placental surface. The total cardiac dimension,
      maximum blood flow velocity of the ascending aorta and the pulmonary artery in
      the alive twin were in the normal range.

PMID- 8250762
TI  - Treatment failure in malignant gestational trophoblastic disease.
AB  - One hundred and thirty-three patients with malignant gestational trophoblastic
      disease (GTD) were admitted. All patients (86/86) of the nonmetastatic and
      metastatic low-risk groups and 89.4% (42/47) of the metastatic high-risk group
      showed remission. The overall remission rate was 96.2%. Among 5 patients with
      brain metastases, however, only one (20%) survived. We arrived at two main
      conclusions. First, brain metastatic lesions did not successfully respond to
      therapy utilizing conventional chemotherapeutic regimens. Second, the key factors
      for successful outcome in brain metastases were early diagnosis and aggressive
      initial therapy. Therefore, early detection of brain metastases should be made
      with: (1) fine computerized tomography (CT) or magnetic resonance imaging (MRI),
      (2) measurement of the ratio of serum to cerebrospinal fluid hCG concentration,
      and (3) early recognition of their clinical features.

PMID- 8250763
TI  - Tubo-ovarian abscess containing tapeworm proglottids and ova: a case report.
AB  - We report a case of pelvic inflammatory disease complicated by a tubo-ovarian
      abscess containing Taenia spp. proglottids and ova which migrated through a
      fistula with the sigmoid colon.

PMID- 8250764
TI  - Shared antenatal care between family health services and hospital (consultant)
      services for low risk women.
AB  - Four thousand four hundred and seventy-two patients were recruited into a project
      to test the efficacy of a Shared Care System in the management of low risk
      antenatal patients. The patients were scored according to a simple point scoring
      system. Three thousand three hundred and fourty-seven (74.8%) were scored as low
      risk. Fifty point two percent (1,682) of these low risk patients received the
      conventional system of care and acted as controls; while 49.8% (1,665) received
      shared care, where they were seen jointly by midwives, general doctors and
      hospital specialists. It was found that with the use of shared care, there was a
      significant decrease in workload to the hospital specialty clinics. Not only was
      the antenatal diagnostic rate of intrauterine growth retardation (IUGR)
      significantly improved, but the mean gestations at which IUGR, malpresentations,
      and pregnancy induced hypertension were diagnosed were also significantly
      earlier. The number of antenatal cardiotocographs performed, as well as the
      number of hospital admissions and mean duration of stay were decreased in the
      study group. The overall cost savings to the hospital was calculated if the
      shared care system was generally adopted.

PMID- 8250765
TI  - Hormone treatment related bone mineral content changes in Japanese women with
      endometriosis.
AB  - The effects of a GnRH agonist and danazol on bone mineral content (BMC) in
      Japanese women with endometriosis were investigated. Nineteen women with
      laparoscopically confirmed endometriosis were treated with buserelin (900
      micrograms/d administered intranasally, 10 cases) or with danazol (400 mg/d p.o.,
      9 cases) for 6 months. Trabecular BMC of the 3rd lumbar vertebra was measured
      using quantitative computerized tomography before treatment, at the end of
      treatment and 6 months after treatment by the same radiologist who was not
      informed about the drug used. Serum estradiol and the biochemical parameters of
      bone metabolism were also measured. A significant decrease in BMC (10% on
      average; maximum 25.4%) was observed at the end of treatment with buserelin (p <
      0.01) and this loss was only partially recovered 6 months after treatment. In the
      danazol group, however, a slight gain in BMC was observed. Buserelin suppressed
      serum estrogen levels much more than danazol did. Parameters of bone resorption
      tended to increase in the buserelin group. Because treatment with buserelin, but
      not with danazol, was always associated with a significant decrease in BMC at L3,
      repeated usage of buserelin may lead to cumulative bone loss in patients with
      endometriosis.

PMID- 8250766
TI  - Analysis of immunosuppressive mechanism to cytotoxic T lymphocyte generation in
      patients with advanced cancer.
AB  - In vitro activation of cytotoxic T lymphocytes (CTLs) in peripheral blood
      mononuclear cells (PBMCs) of patients with advanced cancer is extremely
      difficult. The proportion of monocytes among PBMCs is high in this type of
      patient. We investigated monocytosis and the mechanism of suppression of CTL
      generation and obtained the following findings. 1. The cell fraction ratios of
      PBMCs were divided into two groups: those with a higher proportion of T cells
      (Group I), and those with a rapid increase in monocytes and a decrease in T cells
      (Group II). 2. CTL generation occurred in Group I, but was either extremely low
      or not observed in Group II. 3. Supernatant from the culture of monocytes
      obtained from Group II remarkably suppressed CTL generation. 4. Statistical
      analysis revealed that the cancer recurrence rate over a 2-year period was
      significantly higher in Group II than in Group I. These findings show that
      monocytes are associated with the recurrence and worsening of cancer.
      Furthermore, the monocytes exert this effect by releasing a humoral factor that
      suppresses CTL activation.

PMID- 8250767
TI  - The development of an enzyme immunoassay for placental tissue protein 17 (PP17)
      and its clinical significance.
AB  - We developed an enzyme immunoassay (EIA) for placental protein 17 (PP17) using
      avidin biotin binding, and measured the serum-PP17 levels of 37 healthy men, 103
      nonpregnant women, 48 pregnant women, and 86 patients with gynecologic
      malignancies. The mean level was 12.8 ng/ml in healthy men and 44.2 ng/ml in
      nonpregnant women (p < 0.05). The calculated upper limit of normal was 97.8 ng/ml
      (mean + 2 sigma). The serum PP17 concentration was remarkedly reduced
      postmenopausally. Pregnant women showed a mean serum level of 19.2 ng/ml, which
      was significantly lower than that of nonpregnant women. Immunoserological results
      strongly suggest that PP17 is produced far more in the normal endometrium than in
      the placentae and decidua. Patients with gynecologic malignancies had obviously
      lower mean serum PP17 levels (8.3-19.9 ng/ml) than those found in healthy
      nonpregnant women. Measurement of the serum PP17 concentration might be useful in
      distinguishing gynecologic malignancies from various normal conditions.

PMID- 8250768
TI  - Immunohistochemical and immunoelectron microscopic study of cytochrome P-450 of
      human fetal livers (P-450HFLa): implications for an onco-feto-placental enzyme.
AB  - Cytochrome P-450 of human fetal livers (P-450HFLa) was demonstrated by the avidin
      biotin immunoperoxidase technique in tissue samples as follows: human fetal
      organs, adult livers, human and cynomolgus placenta, and gynecologic organs which
      were obtained from 40 patients with gynecologic malignancies and 32 patients with
      benign diseases. P-450HFLa was clearly localized in the cytoplasm and membranes
      of the hepatocytes, and the fact was confirmed by an immunoelectron microscopic
      examination. In addition, a semiquantitative assay of staining intensity
      demonstrated that this enzyme tended to decrease with advancing age. These
      findings suggest that hepatic P-450HFLa synthesis is inversely proportional to
      age, and that this enzyme is one of the differentiation antigens. P-450HFLa was
      also detected immunohistochemically in other fetal organs. The present study thus
      confirms that P-450HFLa is not specific to the liver and is ubiquitous even in
      the fetus. Marked positive staining for P-450HFLa was demonstrated in villous
      syncytiotrophoblasts. In contrast, no positive staining was found in the
      cynomolgus-monkey placenta, unlike the case for many other placental antigens.
      These findings lead to the tentative conclusion that P-450HFLa is a feto
      placental enzyme peculiar to humans. P-450HFLa was demonstrated to occur very
      frequently in gynecologic malignancies. The mean positivity rate for all
      gynecologic malignancies was 85%, while the rate was below 25% for benign
      gynecologic diseases, indicating that P-450HFLa is one of the onco-feto-placental
      enzymes. The present study thus suggests that this enzyme could be a promising
      new tumor marker for gynecologic malignancies.

PMID- 8250769
TI  - The sources and biochemical characteristics of cobalamin-binders in human
      amniotic fluid.
AB  - The sources and biochemical characteristics of cobalamin-binders in amniotic
      fluid were investigated. Using gel-permeation chromatography, cobalamin-binder,
      extracted from amniotic fluid at term, was recovered in a single peak with the
      molecular size of haptocorrin. Neonatal saliva also contained only haptocorrin.
      However, neonatal gastric juice contained two types of cobalamin-binders:
      haptocorrin and intrinsic factor. Amniotic fluid in midtrimester contained three
      types of cobalamin-binders: haptocorrin, intrinsic factor, and transcobalamin II.
      The cultured amnion cells secreted mainly apo-transcobalamin II. Concentrations
      of both apo-haptocorrin and salivary amylase in amniotic fluid increased as
      gestation advanced. These results suggest that cobalamin-binder in amniotic fluid
      in midtrimester originates from the fetal salivary gland, fetal gastric mucosa,
      and amnion cells, and that the contribution by the fetal salivary gland increases
      at term, when almost all cobalamin-binders in amniotic fluid are haptocorrin.

PMID- 8250770
TI  - The effect of anxiety state during the Gulf War on the course of labor.

PMID- 8250771
TI  - As it was in the beginning.
AB  - A brief account of the obstacles faced during the introduction of hospital
      accreditation in Australia is provided, with some insight into the politics of
      change in health care. Some observations are made concerning critical elements of
      the accreditation program and the implications for the future of the Australian
      Council on Healthcare Standards.

PMID- 8250772
TI  - Transition to a unit-based quality assurance approach: a description of one
      successful implementation strategy.
AB  - In 1987 the decision was taken by the Nursing Executive at Princess Margaret
      Hospital for Children to substitute the centralized approach to quality assurance
      (QA) with a unit-based system. The strategies used to ensure the successful
      implementation of the new system are discussed--together with the pitfalls
      encountered during the transition phase.

PMID- 8250773
TI  - Quality assurance: measures of maternal knowledge and satisfaction.
AB  - This paper reviews the introduction and results of an Outcome Assessment system
      developed to determine if all women delivering at the Royal Women's Hospital,
      Brisbane were receiving an acceptable level of care. The system involves
      measurement of four outcome variables: nosocomial infection rate; medication
      error rate; accident rate; and a comprehensive patient questionnaire. Scores are
      combined and a monthly Quality of Care Score, and other information including the
      Caesarean delivery rate, bed occupancy rate, number of primiparas in the ward and
      percentage of women who failed to achieve a minimum acceptable score, is prepared
      for each ward. On another level, the system allows midwives to objectively
      evaluate the care provided in their ward by involving each patient's primary
      midwife, clinical nurse consultant and unit manager in the collection and review
      of data. The monthly feedback to wards, the Director of Nursing, Chief Executive
      Officer, Dietitian and Senior Domestic Supervisor has resulted in changes which
      had previously been difficult to achieve.

PMID- 8250774
TI  - Diagnosis related groups: the effect of input error.
AB  - American studies on Diagnosis Related Groups (DRG) coding errors have suggested
      large error rates. However, we are aware of no Australian data on the extent and
      significance of errors in completion and encoding of front sheet
      diagnosis/procedure information on DRG grouping of hospital separations. With the
      imminence of casemix funding in Australia, this topic takes on a greater
      significance. We therefore undertook a pilot research study to assess this. At
      each of three hospitals in the Hunter Area Health Service, NSW (one teaching, one
      acute general district hospital and one rural general practitioner hospital), we
      attempted to sample 150 records. A committee reviewed the charts and assessed
      coding, DRG and Major Diagnostic Category (MDC) error rates. These were 8.1-9.6%
      for DRG allocation and 3.4-5.2% in MDC allocation. Using current casemix funding
      data, one of the hospitals would have suffered a funding shortfall for inpatient
      services of nearly $2 million or 2.6% of total budget at that time. If these
      data, extracted after an exercise to reduce errors in DRG and front sheet coding,
      are representative, then there are major implications for hospital inpatient
      funding if casemix funding is introduced. Major educational exercises are called
      for the further in-depth research may prove useful.

PMID- 8250775
TI  - Introducing total quality management in an area health board.
AB  - It is essential for the health care industry to demonstrate a quality service.
      The Canterbury Area Health Board (CAHB), New Zealand is in the process of
      establishing the principles of Total Quality Management (TQM) and this paper
      addresses the key issues of committing to TQM. Highlighted are the Board's
      implemented programmes, business plan and role of the health care industry.

PMID- 8250776
TI  - An analysis of patient accidents in hospital.
AB  - An analysis of patient accidents occurring at St Vincent's Hospital, Sydney in
      1990 was undertaken using data obtained from the hospital's computerized accident
      database. Ward, age and sex specific fall rates were calculated from a total of
      800 patient-related accidents and incidents reported. Ninety per cent of all
      accidents were falls, the majority occurring in patients over the age of 60
      years. Female patients experienced a significantly greater rate of accidents than
      male patients (P < 0.05). No significant difference in the overall fall rates for
      males and females was found. However males 50 years of age and under were almost
      twice as likely to fall as females in this age group. More than 50% of patients
      who fell sustained an injury; 4% of these were serious injuries. The geriatric,
      neurosciences and HIV wards had the highest rates of patient falls. Nearly 40% of
      falls involved only 77 patients who fell on multiple occasions. Preventative
      strategies are discussed. Patient accident data from other Australian hospitals
      is required for adequate assessment of the incidence of patient accidents.

PMID- 8250777
TI  - It is not widely appreciated that Australia and New Zealand owe their Anglo
      Celtic heritage and language to an early clinical Quality Assurance project.

PMID- 8250778
TI  - Chlorpromazine turns forty.
AB  - It is difficult for the contemporary psychiatrist to comprehend the impact that
      the introduction of chlorpromazine had on psychiatric practice in the early
      1950s. With potent psychotropic medications largely taken for granted, our
      awareness of the limitations of these agents blinds us to the therapeutic
      revolution which they introduced.

PMID- 8250779
TI  - Early intervention in schizophrenia.
AB  - The management of schizophrenia may be characterised by two paradigms. The first
      approaches the schizophrenias as episodic relapsing disorders, where treatment is
      provided through both acute (crisis) care and to achieve prophylaxis. The second
      paradigm, sometimes arising from a failure of the first, is of "rehabilitation",
      involving amelioration of disabilities, occasionally within a framework of
      relative asylum. We would propose a third paradigm of "early intervention",
      involving a combination of medical and psychosocial interventions targeted at
      young, vulnerable people with the aim of preventing or limiting likely social,
      psychological and mental deterioration. Vigorous intervention early in the course
      of illness, early recognition and treatment of relapse and the promotion of
      psychological adjustment to psychotic illness are proposed as key elements of
      this third paradigm.

PMID- 8250780
TI  - Depressive disorders among elderly people in long-term institutional care.
AB  - Depressive disorders are common among old people in residential and nursing
      homes. Outside Australia the prevalence rate for depressive symptoms in homes
      ranges from 30-75% while that for depressive disorders defined by psychiatric
      diagnostic criteria is well over 20% in many nursing home studies. These rates
      are between two and twenty times higher than those found among the elderly living
      at home. Evidence from Australia indicates that a problem of similar magnitude
      exists here. While physical disability is strongly associated with depression in
      these populations, it is not the only factor likely to be responsible for the
      initiation and maintenance of depression among those in long-term care. There is
      an urgent need for studies which will better define likely aetiological and
      maintaining factors for depression in institutional populations, as well as
      controlled trials of both pharmacological treatments and environmental
      improvements. In addition, research is needed to establish whether depression is
      an independent risk factor for mortality among institutional residents.

PMID- 8250781
TI  - Suicide among psychiatric in-patients in the Wellington region.
AB  - To identify risk factors for in-patient suicide, a case-control study of in
      patient suicide was conducted in the Wellington Area Health Board region between
      1984 and 1989 on 27 cases and 86 controls. The risk of in-patient suicide was
      increased among individuals who had been compulsorily admitted, suffered from
      schizophrenia, had a past history of deliberate self harm, had been in hospital
      for more than a month, or were unmarried. Notably, there was no relationship with
      physical health, a history of substance abuse, number of psychiatric admissions
      and time since the last known episode of deliberate self harm. These
      characteristics can assist clinical assessment of individual suicidal risk.
      Further evaluation of the relation of compulsory admission to suicide is
      required.

PMID- 8250782
TI  - Cigarette smoking and psychiatric morbidity in women.
AB  - A random community survey of psychiatric morbidity in adult New Zealand women,
      the Otago Women's Health Survey, investigated the association of cigarette
      smoking with mental health. Of the women interviewed, just over one quarter
      (26.1%) smoked, with one third of these smokers consuming more than 20 cigarettes
      per day. Demographic factors associated with smoking were younger age, lower
      socio-economic status, poor education, caring for preschool children,
      dissatisfaction with female caring roles and financial strife. Psychiatric
      morbidity as measured by the short PSE was statistically associated with smoking.
      The unexpected finding reported here is a higher rate of recovery from their
      psychiatric morbidity amongst women who smoked. This result fits with previously
      reported data indicating that women use cigarette smoking to regulate mood and
      cope with the pressures of relentless child care in the context of strained
      financial resources. The profile of the woman who smokes differed substantially
      from that of the woman who drinks alcohol in a hazardous manner. Different
      preventive strategies are therefore required for these two risky behaviours.

PMID- 8250783
TI  - Prevalence of schizophrenia among women in refuges for the homeless.
AB  - There are considerably more homeless mentally ill men than women. However the
      rate of mental illness among homeless women appears to be relatively greater than
      for men. We found the lifetime prevalence of schizophrenia among a cohort of 54
      women residing in refuges for the homeless in inner Sydney to be approximately
      30%. Only three of the women had a history of prolonged stay in a psychiatric
      institution. Schizophrenic women had resided at the refuges for longer than non
      schizophrenic women.

PMID- 8250784
TI  - Has social psychiatry met its Waterloo? Methodological and ethical issues in a
      community study.
AB  - The first wave of a longitudinal and prospective community study of minor
      psychiatric disorder among a cohort of socially disadvantaged women has been
      completed. The study hopes to extend the social model of depression, as initially
      proposed by Brown and Harris [1], by examining the mediating effects of
      personality factors and social support. Findings from previous studies have been
      largely restricted to associations between variables which may be at least partly
      attributable to methodological limitations in design and measurement techniques:
      specifically, the use of inherently biased sampling methods, single interview,
      retrospective data collection and less standardized diagnostic criteria to
      determine caseness. This paper discusses design strategies which were adopted to
      reduce the confounding between variables resulting from these limitations. The
      effectiveness of these strategies is evaluated in light of some methodological
      and ethical issues which have arisen during the recruitment of participants and
      the first wave of data collection.

PMID- 8250785
TI  - Somatisation as a presentation in depression and post-traumatic stress disorder
      among Cambodian refugees.
AB  - Three Cambodian patients with Depression and Post-traumatic Stress Disorder
      (PTSD) presenting with somatic complaints are described. Their case histories
      support previous observations that somatisation is the most common presentation
      of Cambodian patients with Depression and PTSD. The probable reasons why
      depressed, traumatised Cambodian patients somatise their psychiatric problems are
      discussed. These cases illustrate the difficulties involved in engaging such
      patients in Western style psychotherapy, but show the effectiveness of small
      doses of antidepressants in treating the depressive and post-traumatic stress
      symptoms.

PMID- 8250786
TI  - Variations in therapeutic interventions for Cambodian and Chilean refugee
      survivors of torture and trauma: a pilot study.
AB  - The treatment of refugee survivors of torture and trauma has attracted increasing
      clinical attention. The present study surveyed therapists concerning the emphasis
      that was placed on disclosure of previous traumatic experiences in therapy with
      refugees from Chile and Cambodia. Significant differences were found between the
      two groups with trauma story discussion being judged by therapists to be more
      important to treatment outcome in Chilean patients. The problem of potential
      therapist bias limits definitive conclusions, however we suggest that differences
      in cultural preparedness for psychotherapy aimed at uncovering previous traumatic
      experiences may be the main reason for variations in styles of therapy offered to
      these distinctive ethnic groups. Other possible explanations are differences in
      diagnostic profiles and types of previous traumatic experiences.

PMID- 8250787
TI  - Hostility and anger measures in coronary heart disease.
AB  - Recent research addressing the link between psychological factors and risk of
      coronary heart disease (CHD) has focused on the areas of hostility and anger and
      produced sometimes contradictory results. This study makes use of four
      questionnaire measures of hostility and anger, which were administered to matched
      groups with and without CHD. Quicker experiences of anger with greater verbal
      expression best predicted CHD. The difficulties in teasing out the relative
      contributions of emotional expression, experience and personality using available
      questionnaires are discussed.

PMID- 8250788
TI  - Depression, introversion and mortality following stroke.
AB  - In this study, we examined the influence of clinical depression and personality
      introversion on 15-month mortality following stroke. Ninety-four stroke
      inpatients were examined two months post-stroke for clinical depression and pre
      stroke personality characteristics of neuroticism and introversion. Fifteen
      months later, the vital status of 84 of these patients was able to be determined.
      Seven (8%) of the 84 patients died. Mortality rate increased from non-depressed
      to minor depressed and to major depressed patients (1/48 [2%], 2/21 [10%] and
      3/13 [23%], respectively) (chi 2[trend] = 6.6, df = 1, p = 0.01). Patients who
      died had higher depression symptom scores (mean +/- SD) than survivors (17.7 +/-
      6.0 versus 9.9 +/- 7.1) (p = 0.006). Non-survivors were more introverted (i.e.
      had lower extroversion scores) than survivors (1.7 +/- 1.4 versus 4.2 +2- 2.1) (p
      = 0.004). In multivariate analyses, introversion and depression were
      independently associated with mortality. We conclude that personality
      introversion and depression are associated with increased mortality following
      stroke.

PMID- 8250789
TI  - The influence of spinal cord injury on coping styles and self-perceptions: a
      controlled study.
AB  - Well-controlled research investigating psychological responses following Spinal
      Cord Injury (SCI) is lacking. In addition, much of the literature is based on
      depression following SCI and is dominated by data from the USA. The effects of
      SCI on perceptions of control, self-esteem and coping styles over the first year
      of SCI were investigated. Forty-one acute spinal injured patients and 41 able
      bodied controls matched for age, sex and education completed a variety of
      standardised questionnaires on three occasions over one year. The instruments
      included the Locus of Control of Behaviour Scale, Rosenberg's Self-Esteem Scale,
      and an adapted Mental Adjustment to Cancer (MAC) Scale which measures coping
      styles, including fighting spirit, helplessness/hopelessness and fatalism. The
      SCI group were found to be more external in their perceptions of control, lower
      in self-esteem, and more helpless/hopeless and fatalistic in attitude than the
      controls. The majority of the SCI group had scores reflecting adaptive coping
      styles and intact levels of self-esteem but there were still a substantial
      proportion who displayed maladaptive coping styles (e.g. external locus of
      control, fatalism, helplessness). No differences in scores across time were found
      for either group. Implications for psychological rehabilitation are discussed.

PMID- 8250790
TI  - An international perspective on bereavement related concepts.
AB  - This paper reports on part of a study which was aimed at assessing the views of
      leading researchers, theorists or clinicians working in the field of bereavement
      on key issues including, as reported here, concepts of different forms of grief
      as well as favoured theoretical orientations. Of a range of conceptual models the
      most favoured, by a large margin, were attachment theory and the psychodynamic
      model. The views of the "experts" were canvassed with respect to the use of seven
      selected terms used to denote some variant of the grieving process. There was, on
      the part of the respondents, reasonable support for the syndromes of "delayed",
      "chronic", "anticipatory" and "absent" grief. "Inhibited" and "unresolved" grief
      tended to be described using one of the four terms already supported, while the
      use of the term "distorted grief" attracted little support.

PMID- 8250791
TI  - The psychiatrist in an obstetric/gynaecology hospital: establishing a
      consultation-liaison service.
AB  - The establishment and first six months of a psychiatric consultation-liaison
      service to an Australian obstetric and gynaecology hospital is described.
      Referrals, diagnoses and follow-up of patients are discussed, with case reports
      used to illustrate the types of patients seen. Evaluation of the findings and
      possible future directions for the service are discussed.

PMID- 8250792
TI  - The Edinburgh Postnatal Depression Scale: validation for an Australian sample.
AB  - One hundred and three post-partum women completed the Edinburgh Postnatal
      Depression Scale (EPDS) and were interviewed using the Diagnostic Interview
      Schedule. A cut-off score of 12.5 on the Edinburgh Postnatal Depression Scale
      identified all nine women who reached criteria for major depression. At this
      threshold the sensitivity (the percentage of true "cases" identified) of the EPDS
      was 100%, its specificity (the percentage of true "non-cases" identified as such)
      95.7% and its positive predictive value (the percentage of all those tested as
      positive who were correctly identified as such) 69.2%. Although this study
      supported the validity of the EPDS, a replication of this study on a larger
      sample is suggested.

PMID- 8250793
TI  - The development of the Separation Anxiety Symptom Inventory (SASI).
AB  - Separation anxiety continues to be implicated as an early risk factor to adult
      emotional disorder but recent research findings are somewhat contradictory.
      Inconsistencies in approaches to measuring memories of early separation anxiety
      may have contributed to this lack of clarity. We report the development of a
      brief self-report instrument, the Separation Anxiety Symptom Inventory (SASI),
      which was designed to overcome some of these deficiencies in measurement. The
      SASI was shown to have a coherent factorial structure, high internal consistency
      (Cronbach's Alpha > .80) and test-retest reliability over an average of 24 months
      (Intraclass Correlation Coefficient = .89), with serial scores not being affected
      by changes in contemporaneous anxiety levels. Some index of the validity of the
      measure was achieved by (a) comparing SASI scores of index twins with descriptors
      of their "insecure" behaviours in early life provided by corresponding co-twins;
      (b) comparing SASI scores with retrospective DSM III-R diagnoses of early anxiety
      disorders obtained by structured interviews; and (c) examining SASI scores in
      subjects with histories of school refusal. The SASI provides a useful
      standardised measure which will aid in the further testing of the separation
      anxiety hypothesis of adult emotional disorder.

PMID- 8250794
TI  - Reported early separation anxiety symptoms in patients with panic and generalised
      anxiety disorders.
AB  - Attachment theory has proposed that early separation anxiety is a risk factor for
      adult anxiety disorder, with the recent focus being particularly on panic
      disorder. The results of empirical studies examining this link are, however,
      contradictory, possibly because of inconsistencies across studies in measuring
      memories of early separation anxiety. In the present study, a psychometrically
      sound measure, the Separation Anxiety Symptom Inventory (SASI) was used to
      compare memories of such early symptoms in panic disorder (including those with
      mild phobic-avoidance), generalised anxiety disorder and control subjects.
      Anxiety patients as a group returned higher SASI scores (p < 0.001) with a non
      significant trend for panic disorder patients to score higher than those with
      generalised anxiety. These results suggest that early separation anxiety may be a
      harbinger of adult anxiety and that risk of panic disorder may be higher in the
      most severely affected youngsters. As a risk factor, early separation anxiety
      does not however appear to be uniquely related to adult panic disorder.

PMID- 8250795
TI  - Urinary neopterin quantification indicates altered cell-mediated immunity in
      healthy subjects under psychological stress.
AB  - In an effort to quantify changes in cell-mediated immunity (CMI) in healthy
      subjects under stress, we measured levels of neopterin, a well-validated marker
      of CMI activation, in the urine of medical students undergoing academic
      examinations. Neopterin/creatinine ratios measured on the first day of
      examinations (mean 46 mumol/mol) were significantly lower than those measured two
      weeks before (mean 78 mumol/mol, p = .004). Minimum neopterin production
      coincided with maximum subjective stress, as measured by a visual analogue scale.
      After examinations, neopterin/creatinine ratios rose (means 62 mumol/mol
      immediately after, and 65 mumol/mol two weeks after examinations), and these
      levels were not statistically different from those two weeks before examinations.
      Over this post-examination period, subjective distress was significantly lower
      than at either time point before examinations. We conclude that urinary
      neopterin/creatinine ratios may change significantly during periods of
      psychological stress, indicating concomitant alterations in CMI activation.

PMID- 8250796
TI  - Physiological principles in the treatment of difficulty waking from sleep.
AB  - The case report of a young man with profound difficulty waking from sleep is
      presented. Successful management was predicted and instituted from an
      understanding of the physiological principles of circadian rhythmicity.

PMID- 8250797
TI  - Measuring the specific psychopathology of eating disorder patients.
AB  - Cooper and Fairburn's Eating Disorder Examination (EDE) is a semi-structured
      interview designed to assess the specific psychopathology of eating disorder
      subjects. It was employed in a study of 116 Sydney patients for 2 purposes:
      first, to determine its usefulness in an Australian context; and second, to
      compare patients with anorexia nervosa, bulimia and atypical eating disorder. The
      instrument appears to be quite appropriate for studies in Australia. With respect
      to the second aim, the results emphasize the essential similarity in
      psychopathology between the three diagnostic groups. The relevance of this latter
      finding to the categorisation of eating disorders in the DSM-IV proposals is
      discussed.

PMID- 8250798
TI  - Anorexia nervosa in males: a report of 12 cases.
AB  - The demographic and clinical features of 12 male patients with anorexia nervosa
      were investigated by means of a retrospective analysis of their medical records.
      The clinical characteristics of the male patients were found to be remarkably
      similar to those reported for female patients and our findings concur with
      previously published literature. There appears however to be a greater tendency
      to exercise excessively. The importance of recognising anorexia nervosa in males
      is emphasized.

PMID- 8250799
TI  - The rise and fall of phrenology in Australia.
AB  - In the first half of the nineteenth century phrenology, which was claimed to be
      the first science of the mind, experienced enormous popularity in the western
      world. It gave rise to a widespread movement attracting the attention of the
      professional and lay members of society. In Australia, as elsewhere, it had
      influence in penology and criminology, psychiatry, notions of racial inferiority,
      education, anthropology and popular application. By the second half of the
      nineteenth century, following advances in the knowledge of neuro-anatomy, it
      became relegated to the status of a pseudo-science. As such, it remained popular
      with charlatans and the public well into the twentieth century.

PMID- 8250800
TI  - Psychiatrists' views on abortion.

PMID- 8250801
TI  - Statistics and psychotherapy.

PMID- 8250802
TI  - Ethical standards and clinical practice.

PMID- 8250803
TI  - Clozapine overdose with pronounced neutrophilia: a case report.

PMID- 8250804
TI  - Inquisitorial hearings the answer?

PMID- 8250805
TI  - Ethical principles.

PMID- 8250806
TI  - Leukocyte extravasation: mechanisms and consequences.

PMID- 8250807
TI  - Complex regulation of granulocyte adhesion to cytokine-activated endothelium.
AB  - The adhesion of leukocytes to the endothelium is a hallmark in the development of
      an inflammation. Adhesion is caused by a number of mechanisms that depend upon
      the activation of the endothelium. The adhesion has to be specific for the
      different leukocyte types. I review here recent data with respect to
      polymorphonuclear granulocytes (PMN) adhesion to the endothelium of an
      inflammatory site. I especially focus on the pivotal role of Interferon gamma in
      the regulation of PMN adhesion to the endothelium. It modulates the adhesion of
      PMN caused by activation by other cytokines like IL-1, but does not affect the
      cell surface expression of the known adhesion molecules. I postulate the
      existence of a new class of cell surface modulators of adhesion which participate
      in the multiple step process of cell-cell adhesion.

PMID- 8250808
TI  - Juxtacrine interactions of endothelial cells with leukocytes: tethering and
      signaling molecules.
AB  - The interaction of blood leukocytes with the endothelium of post-capillary
      venules and other vessels involves regulated expression of molecules on both the
      endothelial cell (EC) and the leukocyte. This is true for each of the major
      classes of leukocytes, including lymphocytes, monocytes, and granulocytes.
      Interaction of polymorphonuclear leukocytes (PMNs), a particular subset of
      granulocytes, with cultured human endothelium illustrates this concept and also
      illustrates the diversity of structure, mechanisms of expression, and mechanisms
      of action of the molecules involved. One group of molecules binds, or "tethers",
      the PMN to the EC without requiring PMN activation; P-selectin and E-selectin,
      which are glycoproteins that are expressed by translocation from subcellular
      granules or synthesis under transcriptional regulation, respectively, are
      examples. A second group of molecules activates the PMN by binding to signal
      transducing receptors. Platelet-activating Factor (PAF), a biologically-active
      phospholipid, is an example of this class. Its production is controlled by
      regulation of synthetic enzymes and is induced rapidly (minutes) when EC are
      appropriately stimulated. PAF is translocated to the EC surface, where it
      mediates juxtacrine activation of PMNs by binding to a "7 membrane-spanning"
      receptor. One consequence of juxtacrine activation of PMNs by PAF is functional
      upregulation of CD11/CD18 integrins on the PMN. These integrins bind to
      counterreceptors on the EC, enhancing the avidity of adhesion over that provided
      by P-selectin alone. Thus, combinations of tethering and signaling molecules
      regulate PMN adhesive interactions with EC. Combinations of such molecules also
      regulate other functional responses of the PMNs that are important in
      inflammation. The time-dependent expression of different patterns of tethering
      and signaling molecules by EC provides a general mechanism for differential
      adhesion and activation of different classes leukocytes in acute and subacute
      inflammation.

PMID- 8250809
TI  - Characteristics and possible function of endoglin, a TGF-beta binding protein.
AB  - Endoglin was recently described as a major TGF-beta binding protein on
      endothelial cells. In this review we summarize the experimental data on this
      molecule, discuss some of our own findings, and speculate on its function.

PMID- 8250810
TI  - Eosinophil adhesion receptors.
AB  - Eosinophilic inflammation is often characterized by a paucity of tissue
      neutrophils. A possible explanation of this selective accumulation is utilization
      of different adhesion pathways by the two cell types. Eosinophil adhesion in
      vitro to unstimulated HUVEC is selectively enhanced by IL-5 and IL-3. This
      pathway appears to be Mac-1 dependent. At sites of chronic inflammation an array
      of adhesion molecules are likely to be induced on venular endothelium.
      Eosinophils, like other leukocytes, can potentially utilize all three selectin
      adhesion receptors as well as the immunoglobulin family member ICAM-1. In
      addition, unlike neutrophils, eosinophils express VLA-4 and can use the VLA
      4/VCAM-1 pathway. In vitro IL-4 selectively upregulates VCAM-1 on HUVEC and
      promotes eosinophil transmigration via VCAM-1. However, bronchial biopsies of
      both asthmatics and controls revealed strong expression of E-selectin and ICAM-1
      with very weak expression of VCAM-1. This would suggest that, despite the in
      vitro findings, VCAM-1 is not involved in eosinophil migration into the airways
      in chronic asthma.

PMID- 8250811
TI  - Tumor necrosis factor and interleukin 1 induce expression of the glycolipid
      verotoxin receptor in human endothelial cells. Implications for the pathogenesis
      of the haemolytic uraemic syndrome.
AB  - Activation of the endothelium by TNF or IL-1 results in altered haemostatic
      properties of and leukocyte binding to the endothelium. In haemolytic uraemic
      syndrome, the endothelium of the kidney and sometimes other tissues is severely
      damaged, presumably by a bacterial toxin, verotoxin (VT). In vitro studies have
      demonstrated that endothelial cells become sensitive to this toxin when they are
      exposed to TNF alpha or IL-1, inflammatory mediators which are produced by
      monocytes and mesangial cells and which may play a role in the kidney. In this
      report we demonstrate the influence of inflammatory mediators on the binding of
      VT to endothelial cells. Preincubation of human endothelial cells with TNF alpha
      for 24 h resulted in a ten- to hundred-fold increase of specific binding sites
      for 125I-VT-1. IL-1 and lymphotoxin (TNF beta) also markedly increased VT-1
      binding. An exposure of only 6 h to TNF alpha was already enough to enhance the
      number of VT-1 binding sites on endothelial cells for at least 2 days. In order
      to demonstrate that the increases in VT binding was due to an increase in the
      functional VT receptor, glycolipid extracts of TNF alpha-treated cells were
      analyzed by thin layer chromatography. An increase of globotriaosylceramide (Gb3)
      was observed, suggesting that that preincubation of endothelial cells with TNF
      alpha leads to an increase in Gb3 synthesis in these cells. Inhibition of protein
      synthesis by cycloheximide prevented the increase in VT receptors induced by TNF
      alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8250812
TI  - Endothelial and leukocyte activation in experimental polytrauma and sepsis.
AB  - Vascular endothelial-PMN interactions are critical reactions in the development
      of organ failure. Both cell types are activated by LPS and proinflammatory
      cytokines in sepsis. Reactions that are collectively referred to as endothelial
      activation include expression of procoagulant activity and increased adhesiveness
      of the endothelium for leukocytes. Some parameters, which are related to
      endothelial activation are significantly changed during sepsis and altered by
      anti-TNF therapy (e.g. PAI-1, thrombomodulin), while others (e.g. sELAM) are
      increased by sepsis but not influenced by anti-TNF therapy. Leukocyte activation
      (accompanied by elastase release) leads to rearrangement of the CD11/CD18
      structures and thereby increased adherence.

PMID- 8250813
TI  - Monoclonal antibodies to leukocyte and endothelial adhesion molecules attenuate
      ischemia-reperfusion injury.
AB  - Neutrophils have been implicated as the cause of vascular injury that can lead to
      organ dysfunction and organ failure following a variety of initiating events. In
      particular, neutrophils have been shown to be necessary for vascular or tissue
      damage to occur in ischemia-reperfusion injuries of some organs and in the
      generalized ischemia-reperfusion injury resulting from hemorrhagic shock.
      Adherence of neurotrophils to endothelium or homotypic aggregation of neutrophils
      is thought to be necessary for injuries of this type to occur and these cell-cell
      interactions are mediated by adhesion molecules on both endothelial cells and
      leukocytes. In our completed studies, monoclonal antibodies that recognize
      functional epitopes of the leukocyte CD11/CD18 provided protection from ischemia
      reperfusion injury. In addition, preliminary studies investigating leukocyte L
      selectin and endothelial P-selectin appear to provide protection from ischemia
      reperfusion injury.

PMID- 8250814
TI  - Cytokine regulation of endothelial cell function.

PMID- 8250815
TI  - A novel endothelial cell molecule mediating lymphocyte binding in humans.
AB  - Leukocyte extravasation is critically dependent on proper interactions between
      leukocytes and vascular endothelial cells. Although several molecules mediating
      these interactions have been identified, all the homing phenomena observed in
      vivo cannot be explained on the basis of the known adhesion molecules. To
      discover novel molecules involved in leukocyte migration we have made monoclonal
      antibodies against human endothelial cells. With the help of one such monoclonal
      antibody a novel endothelial cell molecule called vascular adhesion protein-1
      (VAP-1) was found. Uniqueness of VAP-1 is evident on the basis of its expression
      pattern, molecular mass, functional properties and N-terminal amino acid
      sequence. VAP-1 mediates lymphocyte binding to endothelium in peripheral lymph
      nodes, tonsil and inflamed synovium. Therefore, VAP-1 is relevant to
      understanding of the physiologic and pathologic lymphocyte migration in man, and
      may be valuable for dissecting the molecular events of tissue-selective
      lymphocyte homing.

PMID- 8250816
TI  - The adhesion and transendothelial migration of human T lymphocyte subsets.

PMID- 8250817
TI  - Monocyte adherence to human vascular endothelium.
AB  - An acute inflammatory response requires that circulating monocytes bind to and
      migrate across the endothelium of the vessel wall to gain access to inflamed
      sites. Various mediators of inflammation, i.e. cytokines and chemoattractants,
      have been shown to initiate and regulate the margination and extravasation of
      monocytes. This review summarizes evidence that the mechanism underlying the
      initial adhesion of monocytes to normal and cytokine-stimulated endothelial cells
      and their subsequent transendothelial migration are successive events in monocyte
      endothelial cell interaction. Special emphasis is given to the current knowledge
      of the contribution of adhesion molecules belonging to the family of beta 1- and
      beta 2-integrins, the immunoglobulin supergene family and the selectins to such
      cellular interaction. The sequence of events that allow monocytes to attach to,
      migrate over and finally pass the endothelium is discussed in detail.

PMID- 8250818
TI  - High endothelial venules: regulation of activity and specificity.

PMID- 8250819
TI  - Regulation of monocyte and neutrophil entry into the vessel wall.

PMID- 8250820
TI  - Endothelial-monocyte activating polypeptides (EMAPs): tumor derived mediators
      which activate the host inflammatory response.

PMID- 8250821
TI  - Musical self-image and cultural change: Lithuanian minority in Poland case study.
AB  - The paper deals with living systems at the social and individual levels of
      analysis. We examine the individual's perception of membership in an ethnically
      defined social group, in particular the hypotheses regarding the implicit
      definitions of one's own social group elicited from the negatives of perceived
      differences from members of other groups. The specific hypotheses concern the
      relationship between the perceived differences and the geographical distance to
      the group. These hypotheses were tested on the material collected from
      evaluations of Lithuanian folk songs from various regions by Lithuanian minority
      in Poland. In addition to the results being generalizable to other ethnic groups,
      and to perception not restricted to songs but also concerning other aspects of
      culture (allowing mostly categorical judgments), the results are of interest
      because of the statistical methodology used, which involves resampling techniques
      for categorical data.

PMID- 8250822
TI  - [Feline immunodeficiency syndrome--a review].
AB  - A review is given on Feline Immunodeficiency Syndrome with reference being made
      to aetiology, epidemiology, pathogenesis and pathology, clinical symptoms,
      differential diagnosis, immunity, therapy and prophylaxis.

PMID- 8250823
TI  - [The detection of Pasteurella multocida toxin using a commercially available
      ELISA].
AB  - 126 Pasteurella (P.) multocida strains isolated from nasal swabs of pigs were
      investigated for producing toxin, comparing tissue culture (EBL cells) and DAKO
      ELISA-PMT-Kit. With help of ELISA 13 toxigenic P. multocida strains were
      identified, with help of tissue culture 12 strains producing toxin. In 14 of 219
      examined nasal swab bacteria cultures of pigs toxin of P. multocida was detected
      by the commercially available ELISA. Because of an abundant mixed bacteria
      culture in 7 of these 14 swabs suspected colonies of P. multocida could not be
      isolated.

PMID- 8250824
TI  - [Pneumonia diagnosis in living swine using lung lavage].
AB  - In pigs coming from fattening units with tenacious pneumonitis problems the
      attempt was made to find an etiological diagnosis in living pigs by
      bronchoalveolar lavage (BAL) and serological examinations on antibodies against
      Mycoplasma hyopneumonia, Actinobacillus pleuropneumoniae and Influenza-A-virus
      (serotypes H1N1 and H3N2). In some cases the results of the bacteriological
      examinations of the BAL were compared with the post mortem findings. Both methods
      yield similar results. Mycoplasma hyopneumonia could neither be cultured from the
      BAL nor indicated the results of the serological examinations infections with M.
      hyopneumoniae. Pasteurella multocida was isolated from 73% of the BAL-samples.
      Actinobacillus pleuropneumoniae was found in 4 from 90 samples. Positive antibody
      titers against Influenza-virus in most of the sera indicate that the clinical
      course of Influenza is changing from an acute epidemic to an enzootic disease in
      fattening units.

PMID- 8250825
TI  - [In vitro adherence of Pasteurella haemolytica to tracheal mucins and a tracheal
      epithelial cell preparation from cattle].
AB  - Outer membrane protein preparations (OMP) of 11 Pasteurella haemolytica field
      isolates of the serovars A1, A2, A11 and non-typable strains from cattle were
      extracted by N-lauryl-sarcosine sodium salt. Capsular extracts were prepared by
      heat treatment. Both preparations and whole cell suspensions bound to a
      preparation of an epithelial cell wall fraction of trachea and to tracheal mucus
      of cattle. Binding was demonstrated by enzyme linked immunosorbent assay (ELISA).
      Distinct high binding values were shown by the OMP and the capsular extracts of
      the serovar A1-strains.

PMID- 8250826
TI  - [The epidemiological analysis of salmonella infections in cattle--results for the
      east Thuringian region from 1974 to 1992].
AB  - Salmonella which are not Salmonella (S.) typhimurium and not S. dublin were found
      in 192 cases of investigated materials from cattle in the region of Eastern
      Thuringia from 1974 to 1992. There were 29 different S.-Serovars. 135 cases
      belonged to samples of the bacteriological investigation after slaughtering of
      ill animals, 45 cases to fecal samples, 9 cases to dissection of calves and 3
      cases to fetuses after abortion. Only S. enteritidis was isolated from all the
      different materials.

PMID- 8250827
TI  - [The content of ascorbic acid in plasma and in 14 tissues of lambs of different
      ages during normal feeding and feeding restricted from time to time during the
      suckling period].
AB  - In normally fed lambs (group 1) the content of ascorbic acid (AA) in the plasma
      on day 8, 18, 28, 38, 48, 60 and 100 after birth was the same as in lambs, that
      were fed on days 8 to 17 (group 2), 8 to 26 (group 3) and 8 to 35 (group 4) on
      the maintenance level. The restrictive feeding induced for a certain time a
      decrease in the glucose content of the plasma. In the lambs of group 2 and 3
      there was no differences in the content of AA in 14 tissues compared to group 1.
      In the lambs of group 4 the body weight on the 35th day was only 54 and the mass
      of the hypophysis 60, of the lung 55.9, of the liver 51, of the heart 47.2, of
      the spleen 44.7 and of the kidney 38% of that of group 1; there was a tendency to
      a lower content of AA in most tissues. With increasing age the content of AA in
      the cerebrum, in the cerebellum, in the brain stem and in the testicles
      decreased; the highest content in the hypophysis was determined on day 180. The
      regulation of the synthesis of AA in the liver under normal and pathological
      conditions is discussed.

PMID- 8250829
TI  - The developmental profile of lactoferrin in mouse epididymis.
AB  - A sandwich e.l.i.s.a. method was developed to examine the distribution of
      lactoferrin in mouse reproductive tract. The lactoferrin concentration was found
      to be much higher in oviduct, uterus, vagina, vas deferens or epididymis than in
      serum, but the concentration in ovary, testis, seminal vesicle, prostate or
      coagulating gland was comparable with that in serum. The existence of lactoferrin
      in male sexual organs was confirmed by Western-blot analyses for tissue proteins.
      Lactoferrin in male sexual organs was shown to have a molecular mass similar to
      that of the deglycosylated form of lactoferrin purified from mouse uterine
      luminal fluid. Northern-blot analyses for total RNA prepared from male sexual
      organs indicated that only epididymis contained the lactoferrin mRNA. The
      lactoferrin mRNA was found in the prepubertal period and increased with the
      growth of epididymis. The mRNA level in prepubertal epididymis could be
      stimulated by 17 beta-oestradiol, but was not influenced by testosterone.

PMID- 8250830
TI  - Insulin secretion, insulin content and glucose phosphorylation in RINm5F
      insulinoma cells after transfection with human GLUT2 glucose-transporter cDNA.
AB  - The insulin-secretory response to glucose is defective in the RINm5F insulin
      producing tumour cell line. Stable transfection with human low-affinity GLUT2
      glucose-transporter cDNA revealed a significant improvement in stimulus-secretion
      coupling in these insulinoma cells. 3-O-Methylglucose uptake increased 10-fold in
      the concentration range 10-20 mM, whereas non-transfected control cells were
      unresponsive. Northern-blot analysis revealed a 7-fold increase in expression of
      the insulin gene in the GLUT2-transfected RINm5F cell clone T1. In contrast,
      glucokinase and GLUT1 glucose-transporter mRNA gene expression were not affected
      by transfection with GLUT2 glucose-transporter cDNA. The insulin content of
      transfected RINm5F cells was 7-fold higher after tissue culture at high glucose
      concentrations than in non-transfected controls. GLUT2-transfected RINm5F cells
      also regained insulin-secretory responsiveness toward high glucose
      concentrations. Tissue culture for 72 h in 20 mM glucose induced glucokinase
      activity in the GLUT2-transfected RINm5F clone T1, raising the
      glucokinase/hexokinase phosphorylation ratio from 0.2 to 0.6. The experiments
      demonstrate that an increased glucose uptake via a low-affinity glucose
      transporter and an increased metabolic flux rate are important factors in the
      induction of insulin-gene expression and glucokinase activity and thus improved
      glucose-induced biosynthesis and secretion of insulin in RINm5F insulinoma cells.

PMID- 8250828
TI  - Calcium: its modulation in liver by cross-talk between the actions of glucagon
      and calcium-mobilizing agonists.

PMID- 8250831
TI  - Sulphation of proteochondroitin and 4-methylumbelliferyl beta-D-xyloside
      chondroitin formed by mouse mastocytoma cells cultured in sulphate-deficient
      medium.
AB  - Mouse mastocytoma cells were cultured in medium containing [3H]GlcN and
      concentrations of [35S]sulphate varying from 0.01 to 0.5 mM. Intracellular
      [35S]sulphate incorporation increased severalfold from the lowest concentrations,
      reaching a maximum at 0.1-0.2 mM, whereas incorporation of [3H]hexosamine
      remained constant at all sulphate concentrations. Proteo[3H]-chondroitin
      [35S]sulphate was isolated and incubated with chondroitin ABC lyase, yielding 35S
      labelled and/or 3H-labelled delta Di-0S and delta Di-4S disaccharide products.
      The increasing percentage of delta Di-4S was consistent with the increasing
      sulphate incorporation at each higher [35S]sulphate concentration. Examination of
      proteochondroitin [35S]sulphate size by Sepharose CL-6B chromatography indicated
      a range consistent with various numbers of glycosaminoglycan chains on the
      protease-resistant serglycin core protein. Alkali-cleaved chondroitin
      [35S]sulphate products indicated similar size distributions at all sulphate
      concentrations with no indication of preferential sulphation being related to
      smaller or larger size. DEAE-cellulose chromatography of [3H]chondroitin
      [35S]sulphate glycosaminoglycans indicated a random undersulphation as
      [35S]sulphate concentration was lowered. Addition of 4-methylumbelliferyl beta-D
      xyloside to the cultures resulted in a 2-2.5-fold stimulation of [3H]chondroitin
      [35S]sulphate synthesis with formation of beta-xyloside-[3H]chondroitin
      [35S]sulphate which was much smaller, as estimated by Sepharose CL-6B
      chromatography, than the decreased amount of [3H]chondroitin [35S]sulphate
      derived from proteo[3H]chondroitin [35S]sulphate. Much higher concentrations of
      sulphate were necessary to produce sulphation of the beta-xyloside
      [3H]chondroitin comparable with that of proteo[3H]-chondroitin, as indicated by
      chondroitin ABC lyase products and DEAE-cellulose chromatography. The specific
      radioactivities of the [3H]GalN in the proteo[3H]chondroitin [35S]sulphate and
      beta-xyloside-[3H]chondroitin [35S]sulphate were calculated from the 3H and 35S
      c.p.m. of isolated dual-labelled delta Di-4S from each, and indicated that the
      presence of the beta-xyloside resulted in a dilution of the [3H]GlcN by
      endogenous GlcN that was 4 times higher than that of cultures lacking the beta
      xyloside. The higher sulphate concentrations needed for sulphation of beta
      xyloside-chondroitin suggests that the membrane-bound nature of the
      proteochondroitin acceptor in juxtaposition to a chondroitin sulphate
      synthesizing enzyme complex effectively reduces the apparent Km for adenosine 3'
      phosphate 5'-phosphosulphate.

PMID- 8250832
TI  - Lipoxin synthase activity of human platelet 12-lipoxygenase.
AB  - Human platelets and megacaryocytes generate lipoxins from exogenous leukotriene
      A4 (LTA4). We examined the role of human 12-lipoxygenase (12-LO) in lipoxin
      generation with recombinant histidine-tagged human platelet enzyme (6His-12-LO),
      partially purified 12-LO from human platelets (HPL 12-LO) and, for the purposes
      of direct comparison, permeabilized platelets. Recombinant and HPL 12-LO
      catalysed the conversion of intact LTA4 into both lipoxin A4 (LXA4) and lipoxin
      B4 (LXB4). In contrast, only negligible quantities of LXA4 were generated when
      recombinant 12-LO was incubated with the non-enzymic hydrolysis products of
      LTA4.6His-12-LO also converted a non-allylic epoxide, 5(6)-epoxy-(8Z,11Z,14Z)
      eicosatrienoic acid. The apparent Km and Vmax. for lipoxin synthase activity of
      6His-12-LO were estimated to be 7.9 +/- 0.8 microM and 24.5 +/- 2.5 nmol/min per
      mg respectively, and the LXB4 synthase activity of this enzyme was selectively
      regulated by suicide inactivation. Aspirin gave a 2-fold increase in lipoxin
      formation by platelets but did not enhance the conversion of LTA4 by the
      recombinant 12-LO. These results provide direct evidence for LXA4 and LXB4
      synthase activity of human platelet 12-LO. Moreover, they suggest that 12-LO is a
      dual-function enzyme that carries both oxygenase and lipoxin synthase activity.

PMID- 8250833
TI  - Studies of the active site of m-calpain and the interaction with calpastatin.
AB  - Calpain autolyses in the presence of Ca2+. In the case of m-calpain (80 + 30 kDa)
      the first product is an 80 + 18 kDa species which has an intact large subunit and
      the C-terminal Ca(2+)-binding domain of the small subunit. It was possible to
      bind E64 into the active site of calpain in the presence of Ca2+ before cleavage
      of either calpain subunit. This suggests that the active site is functional
      before any autolysis has occurred and that calpain is not a proenzyme. Prolonged
      autolysis generates several fragments including a 42 kDa active-site domain
      fragment that showed no proteolytic activity and Ca(2+)-binding domain fragments.
      Some of the Ca(2+)-binding domain fragments were found to exist as heterodimers
      (23 + 18 kDa and 22 + 18 kDa), with the Ca(2+)-binding domain of the large
      subunit interacting with the Ca(2+)-binding domain of the small subunit. These
      species were true heterodimers, as they showed co-elution of the two Ca(2+)
      binding domains on ion-exchange and gel-filtration chromatography, and
      immunoprecipitation of both polypeptides with an antiserum specific for the small
      subunit Ca(2+)-binding domain. The generation of the dimer species after only 15
      min autolysis suggests that the interaction between the Ca(2+)-binding domains is
      present in the native calpain structure. The interaction of calpain with
      calpastatin was investigated using an assay based on binding to calpastatin
      Sepharose and a competitive binding assay. Calpain, active-site-blocked calpain
      and calpain fragments generated by autolysis were studied. Calpain bound to
      calpastatin in the presence of Ca2+; however, the isolated active-site-containing
      80 kDa large subunit (proteolytically inactive), a 42 kDa active-site-containing
      fragment (proteolytically inactive) and Ca(2+)-binding domain fragments of
      calpain did not. Active-site-blocked calpain bound to calpastatin, but with an
      affinity reduced by approximately two orders of magnitude when compared with
      native calpain.

PMID- 8250834
TI  - Construction of a cDNA encoding the multifunctional animal fatty acid synthase
      and expression in Spodoptera frugiperda cells using baculoviral vectors.
AB  - A cDNA encoding the 2505-residue multifunctional rat fatty acid synthase has been
      constructed and expressed as a catalytically active protein in Spodoptera
      frugiperda (Sf9) cells using Autographa californica nuclear polyhedrosis virus
      (baculovirus). The 7.5 kb cDNA was engineered by the amplification and sequential
      splicing together of seven fragments contained in overlapping cDNAs that
      collectively spanned the entire rat fatty acid synthase coding sequence. The full
      length cDNA was cloned into a baculoviral transfer vector and used together with
      linearized baculoviral DNA to co-transfect Sf9 cells. Recombinant viral clones
      were purified and identified by Western blotting. The recombinant fatty acid
      synthase was expressed maximally 2 days after infection of the Sf9 cells,
      constituting up to 20% of the soluble cytoplasm, and could be conveniently
      separated from the insect host fatty acid synthase by high-performance anion
      exchange chromatography. The catalytic properties of the purified recombinant
      fatty acid synthase are indistinguishable from those of the best preparations of
      the natural protein obtained from rat liver. These results indicate that, in the
      insect cell host, all seven catalytic components of the 2505-residue recombinant
      fatty acid synthase fold correctly, the acyl-carrier-protein domain is
      appropriately phosphopantetheinylated post-translationally, and the
      multifunctional polypeptide forms catalytically competent dimers. Thus the
      baculoviral system appears to be well suited for the expression of specific fatty
      acid synthase mutants that can be used to explore the mechanism by which the
      seven domains of this multifunctional homodimer co-operate in the biosynthesis of
      fatty acids.

PMID- 8250835
TI  - Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new kinase
      connections in insulin and growth-factor signalling.
AB  - The beta-isoform of glycogen synthase kinase-3 (GSK3 beta) isolated from rabbit
      skeletal muscle was inactivated 90-95% following incubation with MgATP and either
      MAP kinase-activated protein kinase-1 (MAPKAP kinase-1, also termed RSK-2) or p70
      S6 kinase (p70S6K), and re-activated with protein phosphatase 2A. MAPKAP kinase-1
      and p70S6K phosphorylated the same tryptic peptide on GSK3 beta, and the site of
      phosphorylation was identified as the serine located nine residues from the N
      terminus of the protein. The inhibitory effect of Ser-9 phosphorylation on GSK3
      beta activity was observed with three substrates, (inhibitor-2, c-jun and a
      synthetic peptide), and also with glycogen synthase provided that 0.15 M KCl was
      added to the assays. The results suggest that Ser-9 phosphorylation underlies the
      reported inhibition of GSK3 beta by insulin and that GSK3 may represent a point
      of convergence of two major growth-factor-stimulated protein kinase cascades.

PMID- 8250836
TI  - Inhibition of glutathione synthesis increases the toxicity of oxidized low
      density lipoprotein to human monocytes and macrophages.
AB  - Macrophages are thought to play an important role in the pathogenesis of
      atherosclerosis by mediating the oxidation of low-density lipoprotein (LDL).
      However, it is known that these cells show elevated glutathione levels after
      exposure to oxidized LDL. Here we demonstrate that this increase in the level of
      intracellular glutathione is due to synthesis de novo stimulated by oxidized LDL.
      Furthermore, inhibition of glutathione synthesis renders oxidized LDL cytotoxic
      to both monocytes and macrophages at a concentration well tolerated by untreated
      cells. The stimulation of cholesterol esterification in macrophages by low, non
      toxic, concentrations of oxidized LDL is enhanced under conditions where
      glutathione synthesis is inhibited. These results suggest that the glutathione
      status of macrophages in the artery wall could be important in both controlling
      foam-cell formation and the detoxification of oxidized LDL.

PMID- 8250837
TI  - 2',5'-Oligoadenylate-dependent RNAse located in nuclei: biochemical
      characterization and subcellular distribution of the nuclease in human and murine
      cells.
AB  - A cellular fractionation procedure allowed the rapid preparation of membraneless
      nuclei which contained a 2',5'-oligoadenylate (2-5A)-binding activity which was
      not due to cytoplasmic contaminants. Purified nuclei prepared from human
      lymphocytic leukaemia cells and mouse fibroblasts were found to contain 20-22% of
      the total cellular enzyme. In contrast with the cytoplasmic enzyme which was only
      present in a 2-5A-free form, 75% of the 2-5A-binding activity was found in the
      nuclei after a denaturing-renaturing procedure as the 2-5A-binding site was
      masked. Although the purification of nuclei from mouse fibroblasts was less
      effective, it appeared that, in confluent and growing cells, 50% and 75%
      respectively of the 2-5A-binding site was masked. Additional findings obtained by
      partial proteolysis and two-dimensional gel analysis provided definitive data on
      the nuclear location of this enzyme. Study of the nuclear 2-5A-dependent RNAase
      with a 2-5A-masked site could lead to an understanding of the molecular pathway
      involved in single-stranded RNA stability.

PMID- 8250838
TI  - In vitro translation of androgen receptor cRNA results in an activated androgen
      receptor protein.
AB  - Translation of androgen receptor (AR) cRNA in a reticulocyte lysate and
      subsequent analysis of the translation products by SDS/PAGE showed a protein with
      an apparent molecular mass of 108 kDa. Scatchard-plot analysis revealed a single
      binding component with high affinity for R1881 (Kd = 0.3 nM). All AR molecules
      synthesized specifically bound steroid. No evidence for AR phosphorylation during
      in vitro synthesis was found. When AR was labelled with [3H]R1881 and analysed on
      sucrose-density gradients, a complex of approx. 6 S was observed. The complex was
      shifted to a higher sedimentation coefficient after incubation with a monoclonal
      AR antibody directed against an epitope in the DNA-binding domain. In the
      presence as well as the absence of hormone, AR molecules were able to bind to DNA
      cellulose without an activation step. Gel retardation assays revealed that the AR
      forms complexes with a DNA element containing glucocorticoid-responsive
      element/androgen-responsive element sequences. Receptor-DNA interactions were
      stabilized by different polyclonal antibodies directed against either the N- or C
      terminal part of the AR and were abolished by an antibody directed against the
      DNA-binding domain of the receptor. In conclusion, translation of AR cRNA in
      vitro yields an activated AR protein which binds steroid with high affinity. It
      is proposed that AR antibodies enhance AR-DNA binding by stabilizing AR dimers
      when bound to DNA.

PMID- 8250839
TI  - Stimulation of secretion in permeabilized PC12 cells by adenosine 5'-[gamma
      thio]triphosphate: possible involvement of nucleoside diphosphate kinase.
AB  - The addition of Ca2+, adenosine 5'-[gamma-thio]triphosphate (ATP[S]) or guanosine
      5'-[gamma-thio]triphosphate (GTP[S]) to digitonin-permeabilized PC12 cells
      stimulates noradrenaline secretion. Both ATP[S] and GTP[S] stimulate release in
      the absence of Ca2+. Whereas ADP and adenosine 5'-[beta gamma-imido]triphosphate
      inhibited ATP[S]-stimulated release, they did not inhibit Ca(2+)-stimulated
      release even in the absence of added ATP. This suggests that the kinase which
      uses ATP[S] to induce secretion may not play an essential role in Ca(2+)
      stimulated release. As GTP[S]-stimulated and ATP[S]-stimulated secretions were
      not additive, it seemed possible that stimulation by ATP[S] might in part result
      from the thiophosphorylation of GDP by nucleoside-diphosphate (NDP) kinase to
      form GTP[S]. The following results are consistent with this possibility. (1) A
      low concentration of GDP increased ATP[S]-stimulated secretion, but not GTP[S]
      stimulated or Ca(2+)-stimulated secretion. (2) A variety of ribo- and deoxyribo
      nucleoside di- and tri-phosphates inhibited ATP[S]-stimulated secretion, but not
      GTP[S]-stimulated or Ca(2+)-stimulated secretion. Thus, like NDP kinase, the
      kinase which uses ATP[S] to cause noradrenaline release appears to have a very
      low specificity for ATP. (3) Incubation of permeabilized cells in a sucrose
      containing buffer resulted in the preferential loss of ATP[S]-stimulated
      secretion and a decrease in the level of NDP kinase. The addition of rat liver
      NDP kinase to those depleted cells partially restored ATP[S]-stimulated
      secretion.

PMID- 8250840
TI  - Modulation of iron metabolism in monocyte cell line U937 by inflammatory
      cytokines: changes in transferrin uptake, iron handling and ferritin mRNA.
AB  - We have investigated the effects of the pro-inflammatory cytokines interleukin 1
      beta (IL-1 beta), tumour necrosis factor alpha (TNF alpha) and interferon gamma
      (IFN gamma) on the iron metabolism of the human monocytic cell line U937. Cells
      were treated with each cytokine for up to 24 h, and then iron uptake from
      diferric transferrin was determined. The intracellular distribution of this iron,
      the expression of the transferrin receptor and levels of mRNA for the two
      ferritin subunits were also studied. IL-1 beta, TNF alpha and IFN gamma all
      decreased transferrin-iron uptake into cells, and all three cytokines had effects
      on the proportion of iron associated with ferritin. With TNF alpha there was a
      marked enhancement of the fraction incorporated into ferritin. Transferrin
      receptor expression was diminished by TNF alpha and IL-1 beta, but not IFN gamma,
      suggesting different effector mechanisms. Both TNF alpha and IFN gamma increased
      the amount of cellular mRNA for ferritin H-chain, but not the L-chain; IL-1 beta
      affected mRNA for neither ferritin. These data demonstrate that cytokines, which
      can be present at high concentrations in inflammation, have the capacity to
      affect macrophage iron uptake, transferrin receptor expression, intracellular
      iron handling and the relative abundance of ferritin-subunit mRNA, and may
      therefore be important mediators in the observed perturbations of iron metabolism
      in inflammatory diseases.

PMID- 8250841
TI  - Rapid induction of microsomal delta 12(omega 6)-desaturase activity in chilled
      Acanthamoeba castellanii.
AB  - The activity of microsomal delta 12-desaturase in Acanthamoeba castellanii was
      increased after growing cultures were chilled from the optimal growth temperature
      (30 degrees C) to 15 degrees C. This increase was detectable in microsomes
      isolated from organisms subjected to only 10 min chilling. The mechanism of
      induction was investigated. The increase in activity on chilling was greatly
      reduced when protein synthesis was blocked before the temperature shift. Thus the
      major mechanism for the induction of delta 12-desaturase is increased protein
      synthesis. delta 12-Desaturase activity was higher when assayed at 20 degrees C
      than when assayed at 30 degrees C, but these changes were not due to the
      increased solubility of O2 at 20 degrees C. The major substrate of delta 12
      desaturase was found to be 1-acyl-2-oleoyl phosphatidylcholine.

PMID- 8250842
TI  - Reversible modification of rat liver glutathione S-transferase 3-3 with 1-chloro
      2,4-dinitrobenzene: specific labelling of Tyr-115.
AB  - Rat liver glutathione S-transferase 3-3 (GST, EC 2.5.1.18), a triple mutant with
      all three cysteine residues replaced with serine (CallS) and a quadruple mutant
      with a Tyr-115 to phenylalanine substitution on CallS (CallSY115F) were
      overexpressed in Escherichia coli under the control of a phoA promoter. Using
      this system, we obtained over 35 mg of fully active pure protein/litre of cell
      medium. GST 3-3 and CallS mutant were modified with 1-chloro-2,4-dinitrobenzene
      (CDNB), a model substrate for the enzyme, in the absence of GSH. Dinitrophenol,
      but not S-methylglutathione, inhibits this process. The dinitrophenyl groups are
      readily removed from the enzyme with GSH, but much more slowly with
      dithiothreitol. Results from peptide mapping and amino acid sequence analyses
      indicate that CDNB modifies the cysteine residues and Tyr-115 on wild-type GST 3
      3, but only Tyr-115 on CallS. In addition, CDNB cannot modify the CallSY115F
      mutant. We propose that Tyr-115 is located at or near the H-site of GST 3-3.

PMID- 8250843
TI  - Effects of glucose starvation on the oxidation of fatty acids by maize root tip
      mitochondria and peroxisomes: evidence for mitochondrial fatty acid beta
      oxidation and acyl-CoA dehydrogenase activity in a higher plant.
AB  - Fatty acid beta-oxidation was studied in organellar fractions from maize root
      tips by h.p.l.c. and radiometric analysis of the products of incubations with [1
      14C]octanoate and [1-14C]palmitate. In crude organellar fractions containing both
      mitochondria and peroxisomes, octanoate and palmitate beta-oxidation, as
      determined by the production of acetyl-CoA, was functional and, for palmitate,
      was activated 4-12-fold after subjecting the root tips to 48 h of glucose
      starvation. The sensitivity to a 'cocktail' of respiratory-chain inhibitors
      containing cyanide, azide and salicylhydroxamate depended on the conditions of
      incubation, with no inhibition in a medium facilitating peroxisomal beta
      oxidation and a significant inhibition in a medium potentially facilitating
      mitochondrial beta-oxidation. Indeed, preparations of highly purified
      mitochondria from glucose-starved root tips were able to oxidize octanoate and
      palmitate to give organic acids of the tricarboxylic acid cycle. This activity
      was inhibited 5-10-fold by the above cocktail of respiratory-chain inhibitors,
      with no parallel accumulation of acetyl-CoA, thus showing that the inhibition
      affected beta-oxidation rather than the pathway from acetyl-CoA to the organic
      acids. This provides the first evidence that the complete beta-oxidation pathway
      from fatty acids to citrate was functional in mitochondria from a higher plant.
      Moreover, an acyl-CoA dehydrogenase activity was shown to be present in the
      purified mitochondria. In contrast with the peroxisomal activity, mitochondrial
      beta-oxidation showed the same efficiency with octanoate and palmitate and was
      strictly dependent on glucose starvation.

PMID- 8250844
TI  - Expression of functional human retinol-binding protein in Escherichia coli using
      a secretion vector.
AB  - In order to express human serum retinol-binding protein (sRBP) in Escherichia
      coli in a form that is structurally indistinguishable from the native protein, we
      placed the coding sequence of the RBP cDNA next to that of the outer membrane
      protein A (OmpA) signal sequence in the secretion vector, pIN-III-OmpA1. However,
      this construct did not generate detectable expression of RBP in E. coli. When the
      DNA fragment consisting of the ribosome-binding site and the OmpA-RBP fusion
      sequence was subcloned downstream to the T7 promoter of pKS-Bluescript, however,
      the resultant construct (pOmp-RBP2) gave low but detectable secretion of RBP into
      the periplasm. Deletion of the 3' untranslated region of the RBP cDNA (pOmp-RBP3)
      further improved the expression (by approx. 20-fold). After charging with
      retinol, the secreted RBP was purified from the periplasm on a transthyretin
      affinity resin. The purified protein exhibited all the three molecular
      recognition properties characteristic of sRBP, i.e. it interacted with retinol,
      transthyretin and its cell-surface receptor. Comparison of the receptor binding
      properties of the recombinant RBP (rRBP) with those of the serum protein revealed
      that while the affinity of rRBP is similar to sRBP (50 +/- 20 nM), the Bmax of
      the rRBP is about 6-8-fold higher. This indicates that a major proportion of RBP,
      isolated from serum, is incapable of interacting with the receptor.

PMID- 8250845
TI  - Synthetic RGD peptides derived from the adhesive domains of snake-venom proteins:
      evaluation as inhibitors of platelet aggregation.
AB  - Synthetic peptides based on the RGD domains of the potent platelet aggregation
      inhibitors kistrin and dendroaspin were generated. The 13-amino-acid peptides
      were synthesized as dicysteinyl linear and disulphide cyclic forms. In platelet
      aggregation studies, the cyclic peptides showed 3-fold better inhibition than
      their linear equivalents and approx. 100-fold greater potency than synthetic
      linear RGDS peptides derived from fibronectin. An amino acid substitution, Asp10-
      >Ala, in the kistrin-based peptide gave a 4-fold decrease in potency in the
      linear peptide, but produced a 2-fold elevation in the inhibitory activity of the
      cyclic form, generating a peptide of potency comparable with that of the parent
      protein.

PMID- 8250846
TI  - The regulation of hepatic carbon flux by pyruvate dehydrogenase and pyruvate
      dehydrogenase kinase during long-term food restriction.
AB  - The present study investigated the effects of chronic food restriction (achieved
      by limiting access to food to 2 h daily for up to 8 weeks) on the activity of the
      active form of pyruvate dehydrogenase (PDHa) in liver. Accelerated and
      exaggerated activation of hepatic PDH in response to a meal, previously
      demonstrated to occur within 10 days of food restriction, was demonstrated to
      persist for 4 and 8 weeks of food restriction, despite a food intake of only 50
      60% of controls. Activation of hepatic PDH during feeding in rats subjected to
      food restriction for 4 weeks was dependent on continued food intake. As a
      consequence, hepatic PDHa activities in food-restricted rats were suppressed
      relative to controls for 19 h of the 24 h daily cycle. Curve-fitting by second
      order polynomial regression analysis demonstrated a significant positive
      correlation between hepatic PDHa activity and lipogenic rate over the range of
      PDHa activities observed during the 2 h feeding period. Increased lipogenesis
      during feeding in food-restricted rats was not at the expense of hepatic glycogen
      synthesis or deposition; measurement of concurrent rates of glycogenesis and
      lipogenesis revealed simultaneous flux through both pathways, but specific
      activation of lipogenesis. The accelerated re-activation of hepatic PDH observed
      within 1 h of feeding in rats subjected to 4 weeks of food restriction was
      facilitated by a failure of the 22 h interprandial fasting period to induce a
      stable increase in hepatic PDH kinase activity. The present study indicates
      differential regulation of hepatic PDH kinase activity during periods of food
      withdrawal between food-restricted rats and starved/re-fed control rats. Such
      regulation occupies a critical role in determining the rate of activation of
      hepatic PDH during feeding. In turn, increased activity of hepatic PDHa during
      feeding in food-restricted rats bears a close positive relationship with hepatic
      lipogenic rate.

PMID- 8250847
TI  - Cloning, characterization and import studies on protochlorophyllide reductase
      from wheat (Triticum aestivum).
AB  - A full-length protochlorophyllide reductase clone (pWR5) has been isolated from a
      dark-grown wheat (Triticum aestivum) cDNA library generated in the phage vector
      lambda gt10. Comparison of the sequence of pWR5 with published sequences
      indicates a high degree of conservation of the structure of the mature protein
      amongst species but with the structure of the transit peptide less highly
      conserved. Within the cereals, the structure of the complete preprotein shows a
      remarkable degree of sequence homology (98% between barley and wheat). In vitro
      expression of pWR5 generates a preprotein of the expected molecular mass, approx.
      41 kDa. Isolated pea chloroplasts can import, process and locate the mature
      reductase to the thylakoid membranes. From analysis of the CNBr-cleavage
      fragments of the N-[3H]phenylmaleimide-treated enzyme, the substrate-protected
      cysteine group in the enzyme is tentatively identified as Cys-296.

PMID- 8250848
TI  - Effects of cold environment on mitochondrial genome expression in the rat:
      evidence for a tissue-specific increase in the liver, independent of changes in
      mitochondrial gene abundance.
AB  - The abundance of the mitochondrially encoded mRNA for subunit II of cytochrome c
      oxidase (COII mRNA) increases in the liver of rats exposed to environmental cold
      stress (4 degrees C ambient temperature). Only transient increases or no changes
      in COII mRNA levels were observed in brown fat and soleus muscle respectively.
      The time course of the liver COII mRNA increase was compared with the effects of
      cold stress on mitochondrial 16S ribosomal RNA expression and indicated that cold
      induces a rapid (few hours) increase in the liver mitochondrial mRNA levels and
      high levels of both messenger and ribosomal RNA mitochondrial transcripts are
      present after a few days of cold exposure. No changes in mitochondrial DNA
      abundance relative to total cellular DNA were observed in the liver of rats at
      any time during cold stress. It is concluded that mitochondrial genome expression
      is specifically increased in the liver of cold-exposed rats through different
      mechanisms, independent of changes in mitochondrial genome abundance.

PMID- 8250849
TI  - Mode of action, kinetic properties and physicochemical characterization of two
      different domains of a bifunctional (1-->4)-beta-D-xylanase from Ruminococcus
      flavefaciens expressed separately in Escherichia coli.
AB  - Two catalytic domains, A and C, of xylanase A (XYLA) from Ruminococcus
      flavefaciens were expressed separately as truncated gene products from lacZ
      fusions in Escherichia coli. The fusion products, referred to respectively as
      XYLA-A1 and XYLA-C2, were purified to homogeneity by anion-exchange
      chromatography and chromatofocusing. XYLA-A1 was isoelectric at pH 5.0 and had a
      molecular mass of 30 kDa, whereas XYLA-C2 had a pI of 5.4 and a molecular mass of
      44 kDa. The catalytic activity shown by both domains was optimal at 50 degrees C,
      but XYLA-A1 was more sensitive than XYLA-C2 to temperatures higher than the
      optimum. XYLA-A1 showed a higher sensitivity to pH than XYLA-C2. The enzyme
      activity of both domains was completely inactivated in the presence of copper or
      silver ions and partially inactivated by iron or zinc ions. Neither domain was
      active on xylo-oligosaccharides shorter than xylopentaose: the rate of
      degradation of longer xylo-oligosaccharides (degree of polymerization 5-10)
      increased as the chain length increased. Analysis of the products of hydrolysis
      of xylo-oligosaccharides and xylan (arabinoxylan) polysaccharide showed that the
      two domains differed in their modes of action: xylobiose was the shortest product
      of the hydrolysis. With oat spelt xylan as substrate, XYLA-A1 activity was
      apparently restricted to regions where xylopyranosyl residues did not carry
      arabinofuranosyl substituents, whereas XYLA-C2 was able to release hetero
      oligosaccharides carrying arabinofuranosyl residues. Neither domain was able to
      release arabinose from oat spelt xylan.

PMID- 8250850
TI  - Lipopeptides activate Gi-proteins in dibutyryl cyclic AMP-differentiated HL-60
      cells.
AB  - Synthetic lipopeptides activate superoxide-anion (O2-) formation in human
      neutrophils in a pertussis-toxin (PTX)-sensitive manner, suggesting the
      involvement of G-proteins of the Gi family in the signal-transduction pathway. We
      compared G-protein activation by lipopeptides and the chemotactic peptide N
      formylmethionyl-leucyl-phenylalanine (fMLP) in dibutyryl-cyclic-AMP
      differentiated HL-60 cells. The lipopeptide (2S)-2-palmitoylamino-6
      palmitoyloxymethyl-7-palmitoyloxy heptanoyl-SK4 (Pam3AhhSK4) and fMLP activated
      high-affinity GTPase, i.e. the enzymic activity of G-protein alpha-subunits, in
      HL-60 membranes in a time- and protein-dependent manner, but they had no effect
      on Mg(2+)-ATPase and Na+/K(+)-ATPase. Pam3AhhSK4 and fMLP increased Vmax. of GTP
      hydrolysis. Pam3AhhSK4 activated GTP hydrolysis with half-maximal and maximal
      effects at about 2 microM and 10 microM respectively. Other lipopeptides
      activated GTP hydrolysis as well. Lipopeptides were less effective than fMLP to
      activate GTPase. In membranes from PTX-treated cells, the stimulatory effects of
      lipopeptides and fMLP on GTPase were abolished. In N-ethylmaleimide-treated
      membranes, the relative stimulatory effect of Pam3AhhSK4 on GTP hydrolysis was
      enhanced, whereas that of fMLP was diminished. fMLP and Pam3AhhSK4 activated
      GTPase in an over-additive manner in N-ethylmaleimide-treated membranes. Unlike
      fMLP, Pam3AhhSK4 did not enhance incorporation of GTP azidoanilide into, and
      cholera-toxin-catalysed ADP-ribosylation of Gi-protein alpha-subunits in, HL-60
      membranes and did not induce rises in cytosolic Ca2+ concentration. Pam3AhhSK4
      and fMLP stimulated phosphatidic acid formation in a PTX-sensitive manner.
      Pam3AhhSK4 itself did not activate O2- formation, but potentiated the stimulatory
      effects of fMLP. Our data suggest that (i) lipopeptides activate the GTPase of Gi
      proteins, (ii) lipopeptides and fMLP activate Gi-proteins differently, (iii)
      lipopeptides stimulate phospholipase D via Gi-proteins, and (iv) phosphatidic
      acid formation is not sufficient for activation of O2- formation.

PMID- 8250851
TI  - Lamp-1 does not acquire the large polylactosaminoglycans characteristic of F9
      cells.
AB  - Although F9 cells labelled with [3H]glucosamine synthesize many glycoproteins
      that bind to Datura stramonium agglutinin-agarose, only a small proportion of
      these were immunoprecipitated with monoclonal antibodies to lamp-1 and lamp-2
      (lamp = lysosomal membrane protein). Differentiation of F9 cells by retinoic acid
      increased labelling of all Datura stramonium-bound glycoproteins, including lamp
      1 and lamp-2. Although the large polylactosaminoglycans excluded from Bio-Gel P-6
      that are characteristic of F9 cells were obtained from total glycoproteins,
      little of these large polylactosaminoglycans was found on lamp-1 and lamp-2.
      There was no increase in large polylactosaminoglycans of lamp-1 and lamp-2 after
      retinoic acid treatment, but an increase in the size of small
      polylactosaminoglycans (included on Bio-Gel P-6) and tri- and tetra-antennary
      complex oligosaccharides. Therefore, other factors besides the expression of
      specific glycosyltransferases determine the extent of elongation of
      polylactosaminoglycans on lysosomal membrane proteins.

PMID- 8250852
TI  - A novel ganglioside with a free amino group in bovine brain.
AB  - A novel ganglioside which binds cholera-toxin B-subunit was purified from bovine
      brain by an h.p.l.c. system using an Aquasil column subsequent to Q-Sepharose
      column chromatography. T.l.c./immunostaining showed that the isolated ganglioside
      had about 60% of the binding reactivity of the authentic ganglioside GM1 for
      cholera-toxin B-subunit. On h.p.l.c., this ganglioside migrated between
      ganglioside GD1a and GD1b, and was found to give positive reactions with
      ninhydrin and fluorescamine reagents which specifically react with amino groups.
      The presence of a free amino group was further confirmed by chemical re-N
      acetylation. The N-acetylated product had an identical RF value on h.p.l.c. and
      similar reactivity with cholera-toxin B-subunit as the authentic GM1. H.p.t.l.c.,
      t.l.c./immunostaining, negative-ion fast-atom-bombardment (f.a.b.)-m.s., and 1H
      n.m.r. spectroscopy of the novel ganglioside unequivocally demonstrated that it
      has the basal structure of GM1 with de-N-acetylated neuraminic acid instead of N
      acetylneuraminic acid. In the present study we report for the first time that a
      ganglioside derivative containing de-N-acetylated neuraminic acid, de-N
      acetylated GM1, exists in natural brain tissues.

PMID- 8250854
TI  - Clarification of the nucleotide sequence at the 5'-end of the cDNA for rat liver
      carnitine palmitoyltransferase II.

PMID- 8250853
TI  - Activation of a peroxisome-proliferating catabolite of cholic acid to its CoA
      ester.
AB  - We have shown that a microbial cholic acid catabolite (4R)-4-(2,3,4,6,6a
      beta,7,8,9,9a alpha,9b beta-decahydro-6a beta-methyl-3-oxo- 1H
      cyclopenta[f]quinolin-7 beta-yl)valeric acid (DCQVA), is a potent peroxisome
      proliferator. In this paper a possible key stage in DCQVA metabolism, the
      activation of DCQVA to its CoA ester, has been investigated in rat liver
      microsomes and particulate fractions. The microsomal reaction was dependent on
      CoA, ATP, DCQVA (0.2-1 mM) and protein content. The reaction was decreased by
      storage at 4 degrees C, preincubation of microsomes at 37 degrees C for 5 min, or
      inclusion of Triton X-100 in the reaction mixture. Such treatments also enhanced
      generation of long-chain fatty acyl-CoAs, as determined by h.p.l.c. analysis. The
      same effect was caused by exposing the microsomes to phospholipase A2, suggesting
      that endogenous fatty acids may compete with DCQVA for esterification with CoA.
      Subcellular fractionation of rat liver demonstrated that the activity of DCQVA
      CoA synthesis was localized predominantly in the microsomal fraction, in contrast
      to long-chain fatty acyl-CoA synthetase, which was distributed among all
      particulate fractions. Administration of clofibrate of rats did not affect the
      distribution of DCQVA-CoA synthesis activity. In contrast to a 2-fold induction
      of long-chain fatty acyl-CoA synthetase by clofibrate treatment, the activity of
      DCQVA-CoA synthesis in the microsomal fraction decreased by 80%. These results
      suggest that DCQVA is activated by an enzyme distinct from long-chain fatty acyl
      CoA synthetase. The resulting perturbation of fatty acid metabolism may be
      involved in the mechanism whereby DCQVA causes peroxisome proliferation.

PMID- 8250855
TI  - Ionomycin activates electrogenic Ca2+ influx in rat thymic lymphocytes.
AB  - Increases in intracellular Ca2+ concentration ([Ca2+]i) after addition of the
      carboxylic Ca(2+)-transporting ionophore ionomycin have been reported to be
      inhibited by depolarization in mouse T- and B-lymphocytes, a result attributed to
      effects on the plasma-membrane Ca2+ pump. The present experiments were undertaken
      to test the hypothesis that activation of electrogenic Ca2+ uptake, due to
      release of Ca2+i from intracellular pools, underlies the membrane-potential (Em)
      sensitivity of ionomycin-mediated Ca2+ uptake in T-lymphocytes. To address this
      proposal we have compared the characteristics of Ca2+ influx induced by ionomycin
      with those of Ca2+ influx activated by release of Ca2+ from intracellular stores
      (store-regulated Ca2+ uptake, SRCU). The endosomal Ca(2+)-ATPase inhibitor
      thapsigargin was used to bring about loss of Ca2+ from intracellular pools. In
      support of this hypothesis, we report that: (1) ionomycin releases Ca2+ from a
      thapsigargin-sensitive endosomal pool, a pool previously demonstrated to regulate
      electrogenic SRCU in rat thymic lymphocytes, (2) Ca2+ and Mn2+ uptake mediated by
      low doses of ionomycin are inhibited by compounds previously reported to inhibit
      SRCU, and (3) in the absence of SRCU, ionomycin-mediated Ca2+ uptake displays no
      sensitivity to Em. We conclude that activation of electrogenic SRCU can
      adequately account for the Em-sensitivity of Ca2+ flux previously attributed to
      alterations in Ca(2+)-pump activity. Such a mechanism of action may underlie
      previous reports of electrogenic Ca2+ transport mediated by ionomycin in other
      tissues.

PMID- 8250856
TI  - Isolation and characterization of phosphorylated bovine prolactin.
AB  - Quantitative isolation of bovine prolactin was accomplished by immunoaffinity
      chromatography using clonal antibody as the stationary ligand. The phosphorylated
      and non-phosphorylated (native) prolactins contained in the immunopurified
      preparations were separated by chromatofocusing. Isolates from individual
      pituitaries revealed that phosphorylated prolactin represented between 20 and 80%
      of the total prolactin. The stoichiometry of phosphate in phosphorylated
      prolactin was 1.4:1 when determined by amino acid analysis after preparation of
      the S-ethylcysteine derivative. One major phosphorylation site, serine-90, and
      two minor sites, serine-26 and -34, were determined by mapping and sequencing
      studies. Serine-90 was conserved in prolactins, growth hormones and placental
      lactogens. Serine-26 and -34 were conserved in prolactins, but were not found in
      growth hormones or placental lactogens. Absorption spectroscopy of the aromatic
      amino acid residues indicated that phosphorylation of prolactin was associated
      with a unique structural conformation.

PMID- 8250857
TI  - Affinity labelling of smooth-muscle myosin light-chain kinase with 5'-[p
      (fluorosulphonyl)benzoyl]adenosine.
AB  - 5'-(p-(Fluorosulphonyl)[14C]benzoyl)adenosine (FSBA) was synthesized and used as
      a probe to study the ATP-binding site of smooth-muscle myosin light-chain kinase
      (MLCK). FSBA modified both free MLCK and calmodulin/MLCK complex, resulting in
      inactivation of the kinase activity. Nearly complete protection of the
      calmodulin/MLCK complex against FSBA modification was obtained by addition of
      excess ATP whereas MLCK activity alone was lost in a dose-dependent manner even
      in the presence of excess ATP. These results suggest that FSBA modified ATP
      binding sites and ATP-independent sites, and the latter sites are protected by
      calmodulin binding. The results also suggest that the ATP-binding site is
      accessible to the nucleotide substrate regardless of calmodulin binding. The FSBA
      labelled MLCK was completely proteolysed by alpha-chymotrypsin, and the 14C
      labelled peptides were isolated and sequenced. The sequence of the labelled
      peptide was Ala-Gly-X-Phe, where X is the labelled residue. The sequence was
      compared with the known MLCK sequence, and the labelled residue was identified as
      lysine-548, which is located downstream of the GXGXXG motif conserved among ATP
      utilizing enzymes.

PMID- 8250859
TI  - Mechanism-based inactivation of gastric peroxidase by mercaptomethylimidazole.
AB  - The mechanism of inhibition of gastric peroxidase (GPO) activity by
      mercaptomethylimidazole (MMI), an inducer of gastric acid secretion, has been
      investigated. Incubation of purified GPO with MMI in the presence of H2O2 results
      in irreversible inactivation of the enzyme. No significant inactivation occurs in
      the absence of H2O2 or MMI, suggesting the involvement of peroxidase-catalysed
      oxidized MMI (MMIOX.) in the inactivation process. The inactivation follows
      pseudo-first-order kinetics consistent with a mechanism-based (suicide) mode. The
      pseudo-first-order kinetic constants at pH 8 are ki = 111 microM, k(inact.) =
      0.55 min-1 and t1/2 = 1.25 min, and the second-order rate constant is 0.53 x
      10(4) M-1 x min-1. Propylthiouracil also inactivates GPO activity in the same
      manner but its efficiency (k(inact./ki = 0.46 mM-1 x min-1) is about 10 times
      lower than that of MMI (k(inact./ki = 5 mM-1 x min-1). The rate of inactivation
      with MMI shows pH-dependence with an inflection point at 7.3, indicating the
      involvement in the inactivation process of an ionizable group on the enzyme with
      a pKa of 7.3. The enzyme is remarkably protected against inactivation by
      micromolar concentrations of electron donors such as iodide and bromide but not
      by chloride. Although GPO oxidizes MMI slowly, iodide stimulates it through
      enzymic generation of I+ which is reduced back to I- by MMI. Although MMIOX. is
      formed at a much higher rate in the presence of I-, a constant concentration of I
      maintained via the reduction of I+ by MMI, protects the active site of the
      enzyme against inactivation. We suggest that MMI inactivates catalytically active
      GPO by acting as a suicidal substrate.

PMID- 8250858
TI  - Retinoic acid and cyclic AMP synergistically induce the expression of
      liver/bone/kidney-type alkaline phosphatase gene in L929 fibroblastic cells.
AB  - In L929 mouse fibroblastic cells, liver/bone/kidney type alkaline phosphatase
      (L/B/K-ALP) enzymic activity is induced by all-trans-retinoic acid at
      concentrations between 10(-6) and 10(-5) M. At lower concentrations, retinoic
      acid is incapable of inducing this enzymic activity per se, but increases cyclic
      AMP (cAMP)-mediated induction. This effect is observed after incubation of the
      retinoid with dibutyryl cAMP, 8-bromo cAMP or forskolin. The synergism is
      dependent on the order of addition of retinoic acid and the activator of the cAMP
      pathway. Contemporaneous addition of the two agents, or addition of cAMP prior to
      retinoic acid (but not addition of retinoic acid before cAMP), is necessary to
      produce this synergistic interaction. The synergism results in increased steady
      state levels of L/B/K-ALP mRNA and it is the consequence of increased
      transcriptional activity of the gene. The expression of the mouse L/B/K-ALP gene
      is regulated by the presence of two leader exons, 1A and 1B, resulting in the
      synthesis of two alternatively spliced mRNAs that are different only in part of
      their 5' untranslated region [Studer, Terao, Gianni and Garattini (1991) Biochem.
      Biophys. Res. Commun. 179, 1352-1360]. PCR amplification and nuclear run-on
      experiments performed using probes specific for each leader exon demonstrate that
      treatment of these cells with retinoic acid, forskolin or dibutyryl cAMP, and
      with the combination of the retinoid and one of the cAMP-elevating agents, leads
      to the accumulation of nascent and mature L/B/K-ALP mRNA containing exon 1B. The
      synergistic induction of the transcription of the L/B/K-ALP gene is well
      correlated with quantitative and qualitative changes of retinoic-acid-receptor
      mRNAs mediated by cAMP.

PMID- 8250860
TI  - Kinetic mechanism of activation by cardiolipin (diphosphatidylglycerol) of the
      rat liver multicatalytic proteinase.
AB  - The effect of phospholipids on the trypsin-like, chymotrypsin-like and
      peptidylglutamyl-peptide-hydrolysing activities of the so-called latent form of
      the rat liver multicatalytic proteinase was studied, assaying them with the
      following substrates: N-Cbz-ARR-4MNA (N-Cbz, N-benzyloxycarbonyl; 4MNA, 4-methoxy
      beta-naphthylamide), N-Suc-LLVY-MCA (N-Suc, N-succinyl; MCA, methylcoumarin) and
      N-Cbz-LLE-beta-NA (beta-NA, beta-naphthylamide) respectively (amino acids are
      shown as their one-letter symbol). For the most part neither lysophospholipids
      nor phospholipids at 20 micrograms/ml have any effect on the activity of the
      enzyme (assayed at 50 microM peptide), except for phosphatidylserine, which
      activates 2-fold the hydrolysis of N-Suc-LLVY-MCA, and phosphatidylinositol,
      which inhibits by 20% the hydrolysis of N-Cbz-LLE-beta-NA. By contrast,
      cardiolipin (diphosphatidylglycerol) is a strong activator of the hydrolysis of N
      Suc-LLVY-MCA (60-fold) and N-Cbz-LLE-beta-NA (30-fold), with half-maximal
      activation at concentrations of 0.15 micrograms/ml and 1.5 micrograms/ml
      respectively. The activation of N-Suc-LLVY-MCA hydrolysis is due to an increase
      of the affinity of the enzyme for the peptide and to an increase in the Vmax. (30
      fold). The activation of N-Cbz-LLE-beta-NA hydrolysis is explained by suppressing
      the co-operativity for this substrate, producing hyperbolic kinetics with a Km of
      60 microM and a 15-fold increase in the Vmax. of the enzyme. This activation by
      cardiolipin was completely suppressed by micromolar concentrations of
      fluophenazine, a drug known to inhibit other phospholipid-regulated process.
      Cardiolipin activation and the known activation by SDS are additive, either at
      suboptimal or optimal concentrations of both activators. Cardiolipin also
      activates the in vitro degradation of some proteins from metabolically labelled
      total cellular extracts by the latent multicatalytic proteinase. These results
      clearly show that cardiolipin is a natural positive modulator of the peptidase
      and proteolytic activities of the multicatalytic proteinase, probably acting
      through a binding site different from that of SDS.

PMID- 8250861
TI  - Natural autoantibodies cross-react with a peptide derived from the second
      conserved region of HIV-1 envelope glycoprotein gp120.
AB  - It was recently shown that peptide NTM (RSANFTDNAKTIIVQLNESV), corresponding to
      residues 280-299 in the second conserved domain of HIV-1 envelope glycoprotein
      gp120, has spectral and sequence similarity with human vasoactive intestinal
      peptide, VIP (Veljkovic et al., Biochem. Biophys. Res. Commun., 189, 705-710,
      1992). We found that natural autoantibodies cross-reactive with this peptide can
      be detected in sera from HIV-negative asthma patients and healthy blood donors.
      The level of these antibodies is significantly higher in asthma patients than in
      healthy individuals, suggesting that these antibodies can in fact be at least
      partly identical to natural anti-VIP antibodies previously described (Paul et
      al., Biochem. Biophys. Res. Commun., 130, 479-483, 1985; Paul et al., Science,
      244, 158-1162, 1989). Possible origin and role of these antibodies in AIDS
      pathogenesis and therapy are discussed.

PMID- 8250862
TI  - Efficient gene transfer with less cytotoxicity by means of cationic multilamellar
      liposomes.
AB  - A simple procedure for the preparation of cationic multilamellar vesicles (MLV)
      consisting of N-(alpha-trimethylammonioacetyl)-didodecyl-D-glutamate chloride,
      dilauroyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine in a molar
      ratio of 1:2:2 was devised. When bacteriophage lambda DNA was encapsulated into
      these liposomes, entrapment efficiency was found to be nearly 100%, and
      digestibility of the DNA was less than 10%. Upon encapsulation of the plasmid
      pCH110 into cationic MLV, efficient expression was comparable to that obtained
      with cationic vesicles prepared by reverse-phase evaporation method (REV).
      Cytotoxicity of the present liposomes was less than that of cationic REV and far
      less than that of Lipofectin.

PMID- 8250863
TI  - A cDNA derived from pig bone marrow cells predicts a sequence identical to the
      intestinal antibacterial peptide PR-39.
AB  - We have recently shown that a group of antimicrobial peptides of bovine
      neutrophils share highly identical pro-sequences. In this paper we report the
      cDNA sequence of a 172 amino acid residue pig myeloid protein showing a similar
      pro-sequence of 101 residues. The carboxyl-moiety of the predicted protein is
      identical to the mature form of the proline- and arginine-rich antibacterial
      peptide named PR-39, isolated from pig intestine.

PMID- 8250864
TI  - Localization of protein kinase C in skeletal muscle T-tubule membranes.
AB  - Membrane fractions enriched in transverse tubules, either predominantly free or
      junctional, sarcoplasmic reticulum subfractions and purified sarcolemmal
      preparations have been isolated from rabbit skeletal muscle and examined for
      their contents of protein kinase C. Using activity measurements and
      immunoblotting methods, we have been able to detect substantial amounts of
      endogenous protein kinase C in T-tubules membranes and to a lesser extent, in
      muscle sarcolemma. Protein kinase C was found to be highest in junctional T
      tubules and to be virtually absent from sarcoplasmic reticulum-derived membrane
      fractions. Immunofluorescence staining of muscle fibers is consistent with a T
      tubule localization of the kinase. The T-tubule-associated protein kinase C
      enzyme phosphorylates several potentially important membrane proteins.

PMID- 8250865
TI  - Survival of syngeneic and allogeneic grafted bone in transgenic mice.
AB  - The viability of syngeneic, allogeneic and xenogeneic bone grafts was
      investigated in mice and rats by the polymerase chain reaction method using
      carcinoembryonic antigen transgenic mice as donors. DNA of syngeneic grafts was
      detected more than 24 weeks after bone grafting. In contrast, the DNA of
      allogeneic thymic grafts and xenogeneic bone grafts disappeared by 3 weeks after
      transplantation. However, DNA of allogeneic bone grafts was detected until 20
      weeks after transplantation. Histological examination at 12 weeks after surgery
      detected some donor nuclei in both syngeneic and allogeneic bone grafts.

PMID- 8250866
TI  - Regenerating liver-specific transacting factors of H2B histone gene are newly
      synthesized during liver regeneration.
AB  - We have investigated DNA synthesis and levels of H2B histone mRNA, and the
      binding pattern of nuclear proteins to various elements in the rat H2B histone
      gene upstream region with DNase I footprinting assay. Both DNA synthesis and H2B
      histone mRNA level were increased with maximal stimulation reached at 24 hrs and
      36 hrs after partial hepatectomy, respectively. In DNase I footprinting analysis,
      the nuclear factors interacting with the three elements, TATA at -19 bp (site
      AR), site B at -29 bp, and CAAT at -69 bp (site C) were required during maximal
      increase of H2B histone mRNA level after partial hepatectomy. The DNase I
      protection pattern by nuclear extract of the cycloheximide-treated regenerating
      liver showed the same results with normal liver. These results suggest that
      transcriptional regulation of H2B histone gene during liver regeneration may be
      mediated by nuclear factors that are newly induced by partial hepatectomy.

PMID- 8250867
TI  - Cardiac recovery during post-ischemic reperfusion is improved by combination of
      vitamin E with dihydrolipoic acid.
AB  - Effects of dietary vitamin E supplementation in rats were studied to determine
      whether or not they have a higher tolerance against cardiac ischemia-reperfusion
      injury using the working or Langendorff heart systems. Also, dihydrolipoic acid,
      recently reported to have potent antioxidant properties and accelerate vitamin E
      recycling of membrane in vitro, was perfused into the heart model systems to
      investigate its in vivo relationship with vitamin E. Tissue vitamin E content was
      increased by vitamin E feeding, but heart preparations did not show any improved
      functional recovery. Control hearts perfused with dihydrolipoic acid also did not
      show any improvement. However, a synergistic response is observed with the
      combination of dihydrolipoic acid perfusion and high dietary vitamin E using both
      perfusion systems in improvement of cardiac recovery. These results indicate that
      a high concentration of myocardial vitamin E does not increase tolerance to
      ischemia-reperfusion injury by itself, but, the combination of exogenous
      dihydrolipoic acid and high endogenous vitamin E can produce synergistic
      protective effects on recovery from ischemia during reperfusion.

PMID- 8250868
TI  - Identification of a low molecular mass (14.2 kDa) alpha-tocopherol-binding
      protein in the cytosol of rat liver and heart.
AB  - An alpha-tocopherol-binding protein (TBP) with a molecular mass of 14.2 kDa has
      been identified from the cytosol of rat heart and liver and purified to
      electrophoretic homogeneity by precipitation with 70% ammonium sulphate, followed
      by gel filtration and ion-exchange chromatography. In addition to the 14.2 kDa
      TBP, liver also contains the previously described 30 kDa TBP. The concentrations
      of the 14.2 kDa TBP in heart and liver were 12.3 micrograms and 17.5 micrograms
      per g of tissue, respectively. The purified protein specifically binds d alpha
      tocopherol in preference to the delta- and gamma-homologues but does not bind
      oleate. The TBP stimulated the transfer of d alpha-tocopherol from liposomes to
      mitochondria in vitro by 8-10 fold. These results suggest that low molecular mass
      TBPs may play a role in intracellular vitamin E transport.

PMID- 8250869
TI  - Enhanced expression of the mouse L-histidine decarboxylase gene with a
      combination of dexamethasone and 12-O-tetradecanoylphorbol-13-acetate.
AB  - We previously reported that the induction of L-histidine decarboxylase (HDC) in
      mouse mastocytoma cells was synergistically potentiated with a combination of
      dexamethasone and 12-O-tetradecanoylphorbol-13-acetate (TPA) [Biochim. Biophys.
      Acta, 1133, 172-178 (1992)]. To clarify the molecular mechanism of this
      synergistic action on HDC expression, we have isolated genomic DNA clone (MGH5),
      including 5'-flanking region of the mouse HDC gene. The transcription start site
      and the nucleotide sequences of the promoter regions were determined. We found
      that this clone contains a TATA-like box and a GC-box in the promoter region, and
      several putative binding sites for regulatory proteins in the 5'-flanking region.
      With mastocytoma cells transiently transfected with 5' deletion constructs of HDC
      CAT fusion gene, it was found that the sequence from -267 to -43 is essential for
      the regulatory elements(s) involved in the increased transcription of the HDC
      gene with dexamethasone and TPA.

PMID- 8250870
TI  - Trypsin-resistant regions of thyroglobulin: possible relationship with
      intermonomeric contact site(s).
AB  - Upon incubation of bovine thyroglobulin with trypsin at high enzyme/substrate
      ratio, some fragments with apparent masses between 18 and 31 kDa resisted
      prolonged digestion. Their NH2-terminal sequences were determined. All fragments
      overlapped with some of the Cys-rich repeats that compose a large part of
      thyroglobulin and are predicted to have a rigid structure. Among the inserts that
      interrupt the cysteine-rich repeats, for which several data indicate a location
      at the surface of thyroglobulin, the insert of repeat 1.7 was unique because of
      its resistance to proteolysis. This insert, although exposed at the surface of
      the protein, may be hidden in a region of contact between thyroglobulin monomers.

PMID- 8250871
TI  - Glycogen phosphorolysis can form a metabolic shuttle to support Ca2+ uptake by
      sarcoplasmic reticulum membranes in skeletal muscle.
AB  - In the presence of glycogen, ADP, phosphoglucomutase and hexokinase, the glycogen
      phosphorylase b activity associated to sarcoplasmic reticulum (SR) membranes
      stimulates Ca2+ uptake by SR membrane fragments in the absence of added ATP.
      Phosphoglucomutase and hexokinase lead to the formation of glucose 6-phosphate
      which in turn is used as an ATP regenerating system by the Ca2+ pump. It is
      proposed that a raise of cytosolic AMP and ADP concentrations after muscle
      contraction can activate an alternative metabolic route which would be used to
      ensure the maintenance of a low cytosolic Ca2+ concentration and avoid
      unnecessary metabolic energy depletion in muscle cells.

PMID- 8250872
TI  - Regulation of transient outward K+ current in human atria involves G proteins.
AB  - The role of G protein in regulating the transient outward K+ current (I(to)) was
      examined by using isolated human atrial myocytes. When a nonhydrolyzable analogue
      of guanosine 5'-triphosphate (GTP gamma s) was introduced intracellularly, I(to)
      was irreversibly decreased and reached a new steady-state within 3 minutes. These
      results suggest that regulation of I(to) is similar to that of other K+ current
      in the heart and involves guanine nucleotide-binding proteins. This has important
      implications with respect to autonomic control of action potential duration in
      the human heart.

PMID- 8250873
TI  - Effect of glucose and deoxyglucose on cytoplasmic [Ca2+] in Ehrlich ascites tumor
      cells.
AB  - Concentration of free cytoplasmic Ca2+ ([Ca2+]i) in Ehrlich ascites tumor cells,
      measured using fura-2, amounted to 170-300 nM and was increased by 50-160 nM
      after addition of 10 mM D-glucose or D-2-deoxyglucose but not 3-O-methylglucose
      at pH 7.4. In the range of external pH between 6.8 and 7.8 the increase was
      higher at higher pH. This increase occurred within 30-60 s after addition of
      hexose and lasted for at least 10 min. This [Ca2+]i rise was observed both in
      presence and virtual absence of Ca2+ in the external medium. Pretreatment of the
      cells with thapsigargin resulted in a much smaller [Ca2+]i increase after
      addition of glucose or deoxyglucose. The mechanism of [Ca2+] in the external
      medium. Pretreatment of the cells with thapsigargin resulted in a much smaller
      [Ca2+]i increase after addition of glucose or deoxyglucose. The mechanism of
      [Ca2+]i rise evoked by glucose and deoxyglucose and its importance in switching
      cell metabolism from oxidative to glycolytic are discussed.

PMID- 8250874
TI  - Cytoplasmic-nuclear translocation of the Hsp70 protein during environmental
      stress in Trypanosoma cruzi.
AB  - The present study provides immunological evidence of the constitutive presence of
      the Hsp70 protein in the cytoplasm of logarithmically growing T. cruzi parasites
      cultured at the normal temperature of 28 degrees C and of the translocation of
      the protein to the nucleus upon a heat shock treatment (2 hours at 37 degrees C).
      The nuclear translocation of the protein must depend on other factors beside the
      temperature per se since at 28 degrees C, in stationary phase growing parasites,
      the Hsp70 protein was present in both the cytoplasm and the nucleus. During
      recovery at 28 degrees C the protein leaves the nuclei but the nuclear
      cytoplasmic translocation of the protein is a much more gradual process than its
      initial transport to the nucleus. Since the isoform of the nuclear Hsp70 is
      different from that found in the cytoplasm it is likely that before translocation
      to the nucleus the cytoplasmic Hsp70 nuclear precursor must undergo a specific
      modification.

PMID- 8250875
TI  - Single-channel analysis of a cloned human heart L-type Ca2+ channel alpha 1
      subunit and the effects of a cardiac beta subunit.
AB  - Macroscopic and single-channel properties of a cloned human heart L-type Ca2+
      channel alpha 1 subunit expressed in Xenopus oocytes were studied and the effects
      of a cardiac beta subunit were evaluated. The alpha 1 subunit expressed current
      with much slower activation and inactivation kinetics than native cells. The beta
      subunit increased the current amplitude and accelerated both activation and
      inactivation rates. Single-channel analysis revealed that the beta subunit
      increased the probability of channel opening and shifted the voltage-dependence
      to more negative potentials without affecting conductance or open time. The data
      suggest that the beta subunit modulates macroscopic current by increasing the
      probability of channel opening and shifting the voltage-dependence of the
      channel.

PMID- 8250876
TI  - A novel P-type Cl(-)-stimulated ATPase: phosphorylation and specificity.
AB  - Utilizing a proteoliposomal preparation containing Cl(-)-ATPase, it was
      demonstrated that [gamma-32P]ATP-induced phosphorylation of this pump is by way
      of a relatively low binding affinity while protein dephosphorylation was
      accelerated by increasing concentrations of unlabeled ATP. Ca2+ and Mn2+ were
      also shown to stimulate phosphorylation of the enzyme, but to a much lesser
      extent than Mg2+. Orthovanadate inhibition of enzyme phosphorylation was directly
      related to its concentration. These results suggested that the Cl(-)-pump was a P
      type ATPase similar to that found in plants and fungi based upon its low-affinity
      phosphorylation kinetics.

PMID- 8250877
TI  - Purification and characterization of a Z-Leu-Leu-Leu-MCA degrading protease
      expected to regulate neurite formation: a novel catalytic activity in proteasome.
AB  - A tripeptide aldehyde protease inhibitor, benzyloxycarbonyl(Z)-Leu-Leu-leucinal
      (ZLLLa1), initiates neurite outgrowth in PC12 cells at an optimal concentration
      of 30nM. This result suggests the existence of a protease which regulates neurite
      formation in PC12 cells. We report here an attempt to identify this target
      protease in bovine brain using Z-Leu-Leu-Leu-4-methylcoumaryl-7-amide (ZLLL-MCA),
      in which the aldehyde moiety of ZLLLa1 was changed to 4-methylcoumaryl-7-amide to
      serve as a substrate for the protease. As a result, we have purified a proteasome
      with a molecular weight of about 660 kDa as a ZLLL-MCA degrading protease. The
      activity of the proteasome was inhibited efficiently by ZLLLa1, and was different
      from known catalytic activities of proteasome in some aspects, suggesting it to
      be a novel one. Thus, the proteasome may be involved in the regulation of neurite
      formation in PC12 cells.

PMID- 8250878
TI  - Annexins V and VI in rat tissues during post-natal development: immunochemical
      measurements.
AB  - Annexins V and VI, two Ca(2+)-dependent phospholipid- and membrane-binding
      proteins, were immunochemically measured in a number of rat organs and tissues
      during post-natal development. Annexin V proved much more abundant than annexin
      VI irrespective of the organ and the post-natal period considered. In the brain,
      annexin V accumulated at a high rate from the end of the first post-natal week
      onward, whereas annexin VI was expressed in extremely low amounts irrespective of
      the period investigated. In contrast, the levels of both annexins in the heart
      were nearly constant, in the post-natal period investigated. In skeletal muscles,
      annexin V and VI levels were high around post-natal day 1 and decreased
      thereafter. A similar pattern was observed for annexin V in liver, whereas the
      amounts of annexin VI in this organ were at the limits of detectability. In the
      lung, annexin V accumulated almost linearly from birth to adulthood, whereas
      annexin VI was relatively high at birth, decreased to low levels by the end of
      the first post-natal week, and re-accumulated thereafter. Among the organs
      examined, the lung and heart proved the richest sources of annexins V and VI.
      Annexin V appears to be a useful marker of and to be implicated in brain, lung
      and skeletal muscle maturation.

PMID- 8250879
TI  - A novel mouse gene highly conserved throughout evolution: regulation in adipocyte
      differentiation and in tumorigenic cell lines.
AB  - A cDNA clone referred to as 168 was previously isolated from mouse 1246
      adipocytes by differential hybridization on the basis of its down regulation in
      adipocytes when compared to preadipocytes. 5' RACE was used to obtain a full
      length clone of 761 bp encoding for a highly basic 25 kD polypeptide that is
      extremely conserved in several diverse species of eukaryotes. There is a single
      amino acid substitution at position 202 compared to the human homolog, QM, a
      putative tumor suppressor. Clone 168 mRNA decreases 80% in rat primary culture of
      adipocytes compared to preadipocytes and does not decrease when differentiation
      is blocked by PGF2 alpha or EGF, indicating that the decrease is correlated with
      expression of the differentiation phenotype. Finally, two 1246 cell line variants
      that exhibit altered growth and increased tumorigenicity have a similar level of
      168 mRNA when compared to the non tumorigenic adipogenic parent cell line.

PMID- 8250880
TI  - Formation of inositol (1,4,5) trisphosphate and increase of cytosolic Ca2+
      mediated by Fc receptors in human neutrophils.
AB  - The correlation between the increase of [Ca2+]i and the activation of hydrolysis
      of phosphoinositide-4,5-bisphosphate and formation of
      inositol(1,4,5)trisphosphate in neutrophils treated with Fc receptor-binding
      agonists is still under discussion. In this communication evidence is presented
      supporting the conclusion that, as it is widely accepted for the activation of
      other receptors, also upon the activation of Fc receptors the stimulation of the
      production of inositol(1,4,5) trisphosphate is involved in the increase in
      [Ca2+]i. In fact: i) treatment of neutrophils with immune complexes induced a
      very rapid phosphoinositide hydrolysis measured as [3H]inositol phosphates
      production from [3H]phosphoinositides and as inositol(1,4,5) trisphosphate
      formation measured with radioreceptor assay, ii) immune complexes caused a dose
      dependent increase of [Ca2+]i; iii) the increase of [Ca2+]i correlated with the
      production of inositol(1,4,5) trisphosphate with respect to time course, dose
      dependence and pertussis toxin insensitivity.

PMID- 8250881
TI  - Molecular cloning and structural analysis of canine gastric H+,K(+)-ATPase.
AB  - Gastric hydrogen-potassium ATPase (H+,K(+)-ATPase) is a heterodimeric protein
      which participates in the formation of hydrochloric acid. We cloned canine
      H+,K(+)-ATPase alpha and beta subunit cDNAs from canine gastric cDNA libraries
      and the alpha subunit gene from a canine genomic library. The alpha subunit gene
      is 13 kb in length and contains 21 introns ranging from 77 to 1,076 bp. Its 5'
      flanking region contains putative regulatory motifs for transcription that are
      similar to those found in H+,K(+)-ATPase genes from other species. The open
      reading frames of alpha and beta subunit cDNAs are 3,500 and 870 bp in length and
      encode proteins of 1,034 and 290 amino acids, respectively. They are 80-90%
      homologous to corresponding cDNAs previously identified in porcine and rodent
      gastric tissues.

PMID- 8250882
TI  - Expression of the fungal cytochrome P-450nor cDNA in Escherichia coli.
AB  - We succeeded in expressing the unique cytochrome P-450 (P-450), nitric oxide
      reductase (P-450nor), in Escherichia coli by utilizing P-450nor cDNA and the
      expression vector pKK233-2 or pUC19. The expression was confirmed by Western blot
      analysis and by detecting the unique nitric oxide reductase activity. The
      expressed protein was recovered in the soluble fraction of transformed cells,
      supporting that P-450nor is the first soluble P-450 of eukaryote. The results
      also provided conclusive evidence that the enzymatic reaction depends solely on P
      450nor without support of any other electron transferring components.

PMID- 8250883
TI  - A biochemical marker for differentiation is present in an in vitro aging cell
      system.
AB  - In this study it is shown that in an in vitro aging cell system of human diploid
      fibroblasts the ratio of the histone variants H2A.1/H2A.2 decreases in a linear
      manner as a function of cumulative population doublings This ratio is known to
      decrease during differentiation. This finding reinforces the theory that cellular
      aging is a result of differentiation and programmed cell death rather than
      degeneration.

PMID- 8250884
TI  - Selective effects of mastoparan analogs: separation of G-protein-directed and
      membrane-perturbing activities.
AB  - Mastoparan (MP), a wasp venom peptide, is known both to interact with G-proteins
      and to alter membrane structure and function. To determine the structural
      requirements for these two aspects of MP action, we constructed several analogs
      of the peptide and characterized them using Swiss 3T3 cell membranes. The effects
      of these peptides were measured on: i) G-protein-mediated stimulation of
      phospholipase-C activity by GTP gamma S and bombesin and ii) the membrane enzyme
      activities, calcium-activated phospholipase-C and Na,K-ATPase. MP strongly
      inhibited all the above activities and caused membrane permeabilization.
      Substitution of one Lys residue by Gly at either the N- or C-terminal of the MP
      molecule resulted in peptides which selectively inhibited G-protein stimulated
      phospholipase-C with no or very slight membrane-perturbing effects. Introduction
      of additional Lys residues to MP led to the opposite effect. Thus, G-protein
      modulating and membrane disrupting actions of MP appear to be not necessarily
      linked, and may be separated.

PMID- 8250885
TI  - Formation and release of dinitrosyl iron complexes by endothelial cells.
AB  - The release of dinitrosyl non-heme iron complexes from cytotoxic macrophages
      accounts for NO-mediated iron loss. We have now investigated whether or not a
      similar mechanism operates in endothelial cells. Following stimulation with
      bradykinin or calcium ionophore A23187 NO and intracellular dinitrosyl iron
      complexes were detected by ESR spectroscopic analysis of frozen cells. In
      addition, endothelial cells released dinitrosyl iron complexes which bound to
      extracellular albumin. In transferrin and iron-free medium stimulation of
      endothelial cells by bradykinin or thimerosal resulted in a loss of non-heme
      iron. These effects were prevented by inhibition of NO synthase. Thus NO
      generated by the constitutive NO synthase appears to be incorporated into
      dinitrosyl iron complexes, which potentially account for endothelium-dependent
      relaxation.

PMID- 8250886
TI  - Developmental regulation of aortic elastin gene expression involves disruption of
      an IGF-I sensitive repressor complex.
AB  - Nuclear proteins were isolated from different aged chick embryonic aorta and
      examined by gel mobility shift and footprint analyses using the -195 to +2 bp
      region of the human elastin gene. A major developmental change in DNA/protein
      complexes involved the loss of binding complexes present initially in the 8- to
      11-day nuclear extracts. Both chemical and enzymatic footprinting demonstrated
      that the deprotected binding complexes corresponded to positions -167 to -137 bp
      within the elastin promoter fragment. Gel shift competition assays confirmed the
      identity of the specific DNA sequences affected. These results demonstrate that
      increased elastogenesis during aortic embryogenesis involves the derepression of
      a negative element functionality previously shown to be affected by IGF-I in
      vitro.

PMID- 8250887
TI  - Identification, purification, and characterization of a D-arabinitol-specific
      dehydrogenase from Candida tropicalis.
AB  - A novel D-arabinitol (DA) dehydrogenase was identified and purified more than 300
      fold from Candida tropicalis. The enzyme is specific for DA and catalyzes the
      NAD(+)-dependent oxidation at carbon 4 to yield D-ribulose. Purification was
      accomplished by a combination of protamine sulfate and ammonium sulfate
      precipitation and dye ligand chromatography on a reactive yellow 86 column. The
      apparent Km of the enzyme for DA ([NAD+] = 2.2 mM) is 39.8 mM. The apparent Km
      for NAD+ ([DA] = 384 mM) is 0.12 mM. The pH-optimum for the enzymatic oxidation
      of DA is approximately 10. Cofactor stereospecificity studies demonstrate that
      the enzyme catalyzes transfer of the 4(S) hydrogen of NADH with D-ribulose as
      substrate. The polyol substrate specificity of the present DA dehydrogenase makes
      the enzyme potentially useful for the development of a simple and specific method
      for the measurement of DA, a metabolite of pathogenic Candida spp. which has been
      described as a marker for disseminated candidiasis.

PMID- 8250888
TI  - Glycoprotein of human immunodeficiency virus type 1 synthesized in chronically
      infected Molt3 cells acquires heterogeneous oligosaccharide structures.
AB  - Diversity of oligosaccharide structures on the glycoprotein of HIV-1 was studied
      in individual clones of Molt3 cells chronically infected with HIV-1IIIB. A
      glycoprotein of molecular weight 140 kD (gp140) was found to be shed into the
      medium from one of these clones, which unlike normally processed gp120, contained
      significant proportions of endo H resistant oligosaccharides. Treatment of
      infected cells with the inhibitors of oligosaccharide trimming enzymes affected
      the glycosylation pattern as well as the secretion of the glycoprotein into the
      medium. The exposure of the principal neutralizing domain (PND) on the surface of
      gp140, as measured by its accessibility to thrombin cleavage, was comparable to
      that observed with gp120. Sera obtained from mice inoculated with purified gp140
      contained high titered anti-V3 antibodies and blocked HIV-1IIIB-induced syncytium
      formation. These results demonstrate that although glycosylation of viral
      glycoproteins is governed by the host cell glycosyl transferases, glycoprotein
      secreted from biological clones of the same host cells acquires different
      oligosaccharide structures. Exposure and immunogenicity of the PND in one such
      glycosylation variant are comparable to the normally processed gp120 molecule.

PMID- 8250889
TI  - Modulation of human endothelial cell tetrahydrobiopterin synthesis by activating
      and deactivating cytokines: new perspectives on endothelium-derived relaxing
      factor.
AB  - Endothelial cells, through soluble mediators, play an important role in the
      regulation of the vascular tone. In the present paper we investigated whether
      endothelial tetrahydrobiopterin (BH4), an obligatory cofactor of nitric oxide
      (NO) synthase, could serve as such a regulatory mediator. By studying the human
      vascular endothelial hybrid cells EA hy 926, we found that 1) BH4 biosynthesis is
      highly regulated (70-fold) by activating and deactivating cytokines; that 2) up
      to 90% of the induced BH4 is released by activated endothelium, and 3) while
      intracellular BH4 could be related to cyclic GMP concentrations within the
      endothelial cells, the bulk of BH4 (up to 90 pmol/10(6) cells) appears not to
      serve endothelial cell requirements. Activation and deactivation of BH4 synthesis
      by cytokines was paralleled by other endothelial cell responses reflecting their
      activity. We propose that BH4 serves as an endothelial mediator augmenting the
      activity of cytokine-inducible NO synthase in vascular smooth muscle cells. BH4
      could thereby account for endothelium-derived relaxing factor activity.

PMID- 8250890
TI  - Evidence for alpha-proton abstraction and carbanion formation involving a
      functional histidine residue in lentil seedling amine oxidase.
AB  - Lentil seedling amine oxidase catalyzes the oxidation of putrescine and in the
      presence of tetranitromethane gives rise to the formation of nitroform anion. The
      initial rate of substrate and enzyme-dependent nitroform production is linearly
      related to the functional active site content and is proportional to the
      tetranitromethane concentration. Diethylpyrocarbonate modifies two histidyl
      residues on the lentil amine oxidase. Incubation of the enzyme with
      diethylpyrocarbonate at 25 degrees C and pH 7.0 irreversibly inhibits enzyme
      activity by a pseudo first-order kinetics process. The data obtained are
      consistent with the enzyme-dependent abstraction of an alpha-proton from the
      substrate to form an intermediate enzyme bound carbanion and indicate a
      functional role for histidine in lentil amine oxidase catalysis consistent with
      that of a general base in proton abstraction.

PMID- 8250891
TI  - Internucleosomal DNA cleavage involved in ischemia-induced neuronal death.
AB  - Pyramidal neurons of the hippocampal CA1 are known to be particularly vulnerable
      to transient ischemia resulting in "delayed neuronal death". Recent studies using
      aurintricarboxylic acid suggested that ischemia- or excitotoxin-induced neuronal
      death should share intracellular mechanisms in common with apoptosis. It is,
      however, unclear about involvement of endonucleases. Here using a transient (5
      min) forebrain ischemia model in gerbils, we found that internucleosomal DNA
      fragmentation developed between 48 and 54 hr recirculations, accompanied with
      simultaneous or slightly preceding destruction of microtubule-associated protein
      2. These results suggest that endonucleases, maybe activated by elevated
      intracellular Ca2+, play an important role in delayed neuronal death as well as
      in apoptosis.

PMID- 8250892
TI  - A novel cDNA sequence encoding a pig leukocyte antimicrobial peptide with a
      cathelin-like pro-sequence.
AB  - It has recently been shown that the precursors of various structurally unrelated
      leukocyte antimicrobial peptides share similar pro-regions. These, in turn, are
      highly identical to a cysteine proteinase inhibitor named cathelin, or PLCPI. In
      this paper we report a novel cDNA sequence of porcine bone marrow origin,
      encoding a protein characterized by a cathelin-like domain. The putative protein
      is 147 amino acid residue long, with a calculated mass of 16479 Da and appears to
      be the precursor of a recently isolated antimicrobial peptide named protegrin PG
      2. The unique sequence of the mature PG-2 is located at the C-terminus of the
      precursor. Similar to the previously reported precursors, both the signal peptide
      and the pro-sequence of pre-proPG-2 appear highly conserved.

PMID- 8250893
TI  - Binding site of annexin XI on the calcyclin molecule.
AB  - We purified rabbit calcyclin of S100 family protein and a calcyclin associated
      protein which has proved to be a novel annexin, annexin XI. Using a co
      precipitation assay of annexin XI with phospholipid, the binding site of annexin
      XI on calcyclin was examined. The peptide fragment of calcyclin, CNBr-3 (residues
      1-57), digested with cyanogen bromide completely inhibited the interaction of
      native calcyclin with annexin XI, while CNBr-1 (residues 83-90) and CNBr-2
      (residues 58-82) did not affect the binding. We then constructed and expressed
      recombinant cDNAs for wild type and four different deletion mutants lacking N
      terminal portions. The wild type (wt) and mt1 mutant lacking three amino acids
      from N-terminal bound to annexin XI with phosphatidylserine and Ca2+, whereas
      mt2, mt3 and mt4 with seven, twelve and eighteen amino acids deleted,
      respectively, did not bind to annexin XI. Moreover, the truncated mutant from
      residues 4 to 7 (mt5) decreased the binding capacity. These observations suggest
      that four amino acids (residues 4-7) at the N-terminal portion of calcyclin play
      an important role in the interaction of calcyclin with annexin XI.

PMID- 8250894
TI  - Induction of mononuclear precursor cells with osteoclastic phenotypes in a rat
      bone marrow culture system depleted of stromal cells.
AB  - The importance of bone stromal cell involvement in osteoclast differentiation has
      been suggested. However, the detailed mechanism of its regulation is unclear. We
      investigated whether the soluble factors from osteoblastic cells influence
      osteoclast lineage cells in a population of rat bone marrow cells depleted of
      stromal cells. We show here that hematopoietic progenitor cells differentiate
      into mononuclear precursor cells, the preosteoclasts, that strongly express
      certain osteoclastic phenotypes in the absence of stromal cells. The
      multinucleation of the preosteoclasts occurred only in the presence of 1,25
      dihydroxyvitamin D3 and stromal cells. The preosteoclasts themselves did not have
      dentine-resorbing activity, but they could differentiate into multinucleate
      osteoclast-like cells having such activity in the presence of rat primary
      osteoblasts. This culture system is a unique differentiation system for
      preosteoclast induction.

PMID- 8250895
TI  - Differential regulation of protein kinase C isoenzymes during sphinganine
      potentiation of retinoic acid-induced granulocytic differentiation in human
      leukemia HL-60 cells.
AB  - Differential changes in the expression of PKC isoenzymes in the RA-induced
      differentiation were noted. As measured by Western blot analysis, our results
      indicated the expressions of PKC-alpha, and -beta isoenzymes decreased in the
      cell membrane but increased in the cytosol during the RA-induced granulocytic
      differentiation. The amounts of PKC-gamma, on the other hand, decreased in the
      cell membrane while there was no significant changes in the cytosol. Similarly,
      the expression of PKC-delta was not altered in the cytosol, but was slightly
      reduced during the SP enhancement of RA-induced differentiation. In contrast,
      there were virtually little changes in the expression of PKC-epsilon and -zeta in
      the cell membrane or in the cytosol during the RA-induced differentiation in the
      absence or presence of SP. Concomitant with the decreased total PKC activity,
      there was a decline in the generation of sn-1,2-diacylglycerol (DAG) during the
      RA-induced differentiation. SP, enhancing the RA-induced differentiation, also
      potentiated the decrease of DAG content.

PMID- 8250896
TI  - Formation of farnesal and 3-hydroxy-2,3-dihydrofarnesal from farnesol by
      protoplasts of Botryococcus braunii.
AB  - Farnesal and 3-hydroxy-2,3-dihydrofarnesal (3-hydroxy-3,7,11-trimethyl-6,10
      dodecadiene-1-al) were formed from farnesol when the alcohol was incubated with
      the protoplast of Botryococcus braunii B race strain. This fact suggests the
      existence of farnesal hydratase in the alga. Feeding experiments showed that both
      farnesal and 3-hydroxy-2,3-dihydrofarnesal were efficiently incorporated into
      botryococcenes, triterpenoid hydrocarbons of the alga.

PMID- 8250897
TI  - Cholesterol oxidase: a potent insecticidal protein active against boll weevil
      larvae.
AB  - The discovery of proteins that control insects is critical for the continued
      growth of the agricultural biotechnology industry. A highly efficacious protein
      that killed boll weevil (Anthonomus grandis grandis Boheman) larvae was
      discovered in Streptomyces culture filtrates. The protein was identified as
      cholesterol oxidase (E.C. 1.1.3.6). Purified cholesterol oxidase was active
      against boll weevil larvae at a concentration (LC50 = 20.9 micrograms/ml)
      comparable to the bioactivity of Bacillus thuringiensis proteins against other
      insect pests. Histological studies demonstrated that cholesterol oxidase lysed
      the boll weevil midgut epithelium, suggesting that this is the primary mechanism
      of lethality.

PMID- 8250898
TI  - Expression of the genes encoding the early carotenoid biosynthetic enzymes in
      Capsicum annuum.
AB  - We have shown that both geranylgeranyl pyrophosphate synthase and phytoene
      synthase from pepper and tomato chromoplasts are very similar in terms of enzymic
      activity and immunological properties. This enabled us to clone cDNAs specific
      for phytoene synthase from ripening tomato and pepper fruits and to compare their
      amino acid sequences with those of bacterial phytoene synthase and yeast squalene
      synthase. Comparison of the nucleotide sequence of the 3'-untranslated region of
      the pepper phytoene synthase cDNA suggests that this region was subjected to
      complex recombination events. RNA gel blot hybridizations revealed that induction
      of phytoene synthase gene expression is much stronger in tomato than in pepper
      fruits. In contrast with tomato, 2 phytoene synthase transcripts of different
      size are present in pepper leaves and fruits. Comparison of the expression
      pattern of the genes encoding geranylgeranyl pyrophosphate synthase, phytoene
      synthase and phytoene desaturase revealed that these genes are not co-regulated
      during pepper fruit ripening.

PMID- 8250899
TI  - Bond and molecular polarizabilities in the reactivity studies of uracil and its
      substituents.
AB  - Bond and molecular polarizabilities of uracil and its substituents are determined
      by molecular vibration and quantum mechanical delta-function potential model. The
      longitudinal bond polarizability coefficients of C4-C5, C5-CH3 and C5-NO2 bonds
      confirm that position 5 is partially aromatic while position 4 is aliphatic with
      reference to the reactivity nature of carbon atoms in uracil. The results are
      discussed in relation to experimental and theoretical results.

PMID- 8250900
TI  - The carbohydrate structures of Trypanosoma brucei brucei MITat 1.6 variant
      surface glycoprotein. A re-investigation of the C-terminal glycan.
AB  - We have studied the oligosaccharide chains of the variant surface glycoprotein
      (VSG) of Trypanosoma brucei brucei MITat 1.6. Glycopeptides were generated by
      Pronase digestion, purified by gel permeation and ion-exchange chromatography,
      and structurally characterized by 1H and 31P NMR spectroscopy in combination with
      chemical composition analyses. The two glycopeptide fractions obtained each
      proved to be homogeneous in their peptide and heterogeneous in their carbohydrate
      structures. The fraction representing the "internal" N-glycosylation site of the
      VSG was found to contain high-mannose type oligosaccharides with structures Man7
      9GlcNAc2 linked to Asn-Ala-Thr. The other glycopeptide fraction contained the
      membrane-anchoring C-terminal glycan of the VSG attached to Asp. Its
      oligosaccharide structures are of the glycosylphosphatidylinositol (GPI) type:
      [structure: see text] This structure includes revisions of multiple structural
      features published for the GPI anchor of T. b. brucei MITat 1.6 VSG by Schmitz et
      al. (1987) Biochem. Biophys. Res. Commun. 146: 1055-1063.

PMID- 8250901
TI  - Evidence for singlet oxygen-induced cross-links and aggregation of collagen.
AB  - Singlet oxygen, generated by a hematoporphyrin-photosensitized reaction, was
      shown to cause insolubilization and an increase in molecular weight of acid
      soluble type I collagen and vitreous collagen as manifested in sodium dodecyl
      sulfate polyacrylamide gel electrophoresis. No such changes in the molecular
      properties of collagen could be observed when the irradiation was carried out in
      the presence of sodium azide, a singlet oxygen quencher. The increase in
      molecular weight and insolubilization of the collagen solution was attributed to
      extensive cross-links in the protein molecules.

PMID- 8250902
TI  - Synthesis of omega-agatoxin IVA and its related peptides.
AB  - A potent and selective P type calcium channel blocker isolated from the venom of
      the funnel web spider Agelenopsis aperta, omega-agatoxin IVA, and its related
      peptides were synthesized by the solution procedure. Synthetic omega-agatoxin IVA
      was found to block high-threshold P-type calcium current in rat Purkinje neuron
      with the same potency as that reported for the natural product. Its disulfide
      structure was determined by amino acid analysis, gas-phase sequencing and mass
      spectrometry of the proteolytic fragments. The N-terminus biotinylated and
      truncated peptides showed the same disulfide-bond-forming profile and the same
      activities as those of omega-agatoxin IVA, indicating that the N-terminal basic
      tripeptide, Lys-Lys-Lys, is not important for both the folding and the expression
      of the biological activity. However, the Trp residue in the molecule might be
      essential for the toxin to bind tightly with the channel pores.

PMID- 8250903
TI  - A single protein immunologically identified as CD38 displays NAD+ glycohydrolase,
      ADP-ribosyl cyclase and cyclic ADP-ribose hydrolase activities at the outer
      surface of human erythrocytes.
AB  - The three ectoenzyme activities, NAD+ glycohydrolase, ADP-ribosyl cyclase and
      cyclic ADP-ribose hydrolase were purified to homogeneity from solubilized human
      erythrocyte membranes. The purification procedure involved three sequential
      chromatography steps on hydroxylapatite, immobilized Cu++ and immobilized anti
      CD38 monoclonal antibody resins. The final step yielded a single 46 kDa protein
      displaying all three enzymatic activities. Since the protein bound specifically
      to the anti-CD38 resin, it was immunologically identified as CD38, a 46 kDa
      surface antigen involved in activation and proliferation of lymphocyte
      populations.

PMID- 8250904
TI  - Cloning, sequencing and expression of the gene for alpha antigen from
      Mycobacterium intracellulare and use of PCR for the rapid identification of
      Mycobacterium intracellulare.
AB  - The complete nucleotide sequence of alpha antigen secreted from Mycobacterium
      intracellulare (ATCC13950) was determined. The gene encoded 330 amino acids
      including 40 amino acids for signal peptide, followed by 290 amino acids for a
      mature protein with molecular mass 30,645 Da. The cloned gene was expressed in
      Escherichia coli by using an E. coli expression vector. Based on these results,
      the feasibility of rapid identification of M. intracellulare by two step
      polymerase chain reaction (PCR) was demonstrated.

PMID- 8250905
TI  - Establishment of monoclonal antibodies against human nerve growth factor.
AB  - We have generated and characterized a monoclonal antibody to human nerve growth
      factor (hNGF). The monoclonal antibody NGFA-133 neutralizes hNGF activity, as
      assayed by neurite-outgrowth of nerve cells from chick embryonal dorsal root
      ganglion. Using this antibody, we have developed a sensitive and specific two
      site enzyme immunoassay (EIA) system for hNGF. The assay is based on a
      sandwiching of the antigen between NGFA-133 coated on a microtiter plate and the
      same monoclonal antibody (NGFA-133) conjugated with horseradish peroxidase (HRP).
      The two-site EIA was sensitive enough to detect 920 fg/well of hNGF and did not
      cross-react either human neurotrophin-3 (hNT-3) or sodium dodecyl sulfate (SDS)
      denatured hNGF.

PMID- 8250906
TI  - Stabilization of alpha-helix in C-terminal fragments of neuropeptide Y.
AB  - To elucidate the alpha-helix-stabilizing effect of amino acids at the helical
      ends, we prepared analogs of C-terminal fragments of neuropeptide Y (NPY)
      containing an alpha-helical part. The helix-stabilizing tendency of N-terminal
      amino acid in NPY (12-36) was found to be as follows: Thr > Ser > Gly > Gln > Cys
      > Asn > Asp > Val > Phe > Glu > Lys > Tyr > Ala = Trp > His > Arg, suggesting the
      importance of end capping. The capping effect was not evident when N-termini in
      NPY (11-36) and NPY (13-36) were replaced. Under the same conditions as those for
      the receptor binding, [Thr12]NPY (12-36) had about 4-fold higher alpha-helix
      content than [Arg12]NPY (12-36). However, there was no apparent relationship
      between the helix content and binding affinity to the Y2 receptor.

PMID- 8250907
TI  - Force-generating domain of myosin motor.
AB  - To understand the underlying mechanism of force generation by myosin motor, it is
      crucial to know which part of the molecule is essential for the process. Recent
      structure determination of myosin motor domain at atomic resolution has revealed
      that the domain comprises two smaller domains, the "ATPase domain" consisting of
      only an N-terminal segment of the heavy chain and the "neck domain" consisting of
      a long alpha-helix of the heavy chain and two light chains. This atomic structure
      begs the question of whether both domains are required for force generation. To
      answer it, we genetically truncated the head to generate a recombinant fragment
      composed of the "ATPase domain" alone. The truncated head drove sliding movement
      of actin filaments and generated force in a novel in vitro assay system, which
      allows us to hold a specific site of the head on a glass surface. These results
      indicate that the compact ATPase domain functions as a force-generating machinery
      of the myosin motor.

PMID- 8250908
TI  - Characterization of a monoclonal antibody specific for the Ras-related GTP
      binding protein Rho A.
AB  - The Rho family of small GTP-binding proteins is one of the three subgroups which,
      together with the Ras and Rab families, constitute the Ras-related superfamily.
      The Rho subgroup contains at least seven highly homologous members including 4
      Rho proteins (RhoA, RhoC, RhoB, and RhoG), the Rac1 and Rac2 proteins, and
      CDC42Hs, which are involved in various aspects of cytoskeleton organisation and
      cell polarity. We have raised antibodies to individual members of the Rho family,
      and we report here the characterization of a monoclonal antibody (26C4) specific
      for RhoA. When used in western blot experiments, the 26C4 antibody recognizes the
      recombinant RhoA protein but not the almost identical RhoC or the RhoG, Rac and
      CDC42Hs proteins. Furthermore the 26C4 antibody identifies the natural RhoA
      protein in human lymphocyte cell extracts and was used to study the level of RhoA
      expression in several lymphoblastoid cell lines, and its association with the
      cell membrane.

PMID- 8250909
TI  - Amplification and overexpression of EXP1 and EXP2/Cyclin D1 genes in human
      esophageal carcinomas.
AB  - We previously identified two genes, EXP1 and EXP2/Cyclin D1, about 120 kb apart
      from HST1 and INT2 on human chromosome 11q13. Here we report the frequent
      amplification and overexpression of these genes in surgically resected esophageal
      carcinomas. Amplification was observed in 8 out of 22 cases. In the tumors with
      the amplification, these genes were overexpressed, while in the tumors without
      the amplification, expression levels of these genes were almost the same as those
      with normal mucosa. These results suggest that EXP1 and/or EXP2/Cyclin D1 may
      play an important role in the progression of human esophageal carcinomas.

PMID- 8250910
TI  - Identification of 8-hydroxyguanine glycosylase activity in mammalian tissues
      using 8-hydroxyguanine specific monoclonal antibody.
AB  - Here we report the finding of glycosylase activity in mammalian tissues to remove
      8-hydroxyguanine residues from DNA. To detect this activity, a synthetic duplex
      DNA containing an 8-hydroxyguanine residue was used as the substrate, and before
      the product was analyzed by HPLC-electrochemical detection (ECD), 8
      hydroxyguanine released by the enzymatic action was specifically collected from
      reactions using immunoaffinity columns of 8-hydroxyguanine specific monoclonal
      antibody. With the application of immunoaffinity column chromatography, a single
      peak of 8-hydroxyguanine free from many interfering peaks of unknown origin was
      clearly demonstrated in HPLC-ECD even with crude tissue extracts used as assay
      materials. All the tissues of the rats examined showed the activity, suggesting
      its presence is ubiquitous. The present coupled technique of immunoaffinity
      column chromatography and HPLC-ECD will be very useful to many future studies of
      8-hydroxyguanine glycosylase such as its activity detection, characterization and
      purification, etc.

PMID- 8250911
TI  - Sensitive detection of low levels of ribonuclease H activity by an improved
      renaturation gel assay.
AB  - Renaturation gel assays are good tools to assign enzymatic activities to protein
      bands. First, proteins are separated by denaturating electrophoresis on substrate
      containing gels. Then, following the elimination of the denaturing agent,
      polypeptides are allowed to renature, thus leading to the degradation of the
      embedded substrate at positions at which the corresponding activity has moved.
      Nevertheless, this in situ technique does not only reflect a certain amount of
      enzyme activity, it also depends upon the ability of an enzyme to renature. Here
      we present a renaturation gel assay procedure with an improved sensitivity and
      discuss the detection of E. coli and human ribonuclease H activities as an
      example.

PMID- 8250912
TI  - Two-dimensional gel electrophoretograms of human chromosome specific restriction
      DNA fragments.
AB  - Human genomic DNA can be scanned by a two-dimensional gel electrophoresis of NotI
      cleaved, end-labelled DNA. This method, called Restriction Landmark Genome
      Scanning (RLGS) method yields about 2000 landmark spots in such a two-dimensional
      gel electrophoresis. To assign these spots to chromosomes, DNA from flow-sorted
      chromosome 3 (7.7 x 10(5) copies) and chromosome 4 (6.7 x 10(5) copies) were
      subjected to the same analysis. Ninety seven and 122 spots, respectively, were
      obtained in the electrophoretograms among which 16 spots were common to other
      chromosomes, and the others were unique to each chromosome. A method has been
      devised to assign these spots to the whole genomic profile. The ability to assign
      each spot to a chromosome will render this new mapping technology extremely
      useful, in which one can detect physical aberrations occurring in chromosomes, or
      it can be used as an auxiliary method in physical mapping of the human genome.

PMID- 8250913
TI  - A glial-specific voltage-sensitive Na channel gene maps close to clustered genes
      for neuronal isoforms on mouse chromosome 2.
AB  - A variety of glial cell types express saxitoxin (STX)-binding voltage-sensitive
      Na channels (1,2), although the possible role of impulse conduction in these
      cells is not understood. Gautron et al. (1992) recently identified a 7.5 kb
      species of mRNA in type 1 astrocytes cultured from rat brain cerebrum that
      hybridized with a "common" Na channel probe but not with brain isoform-specific
      cDNA probes. Sequence data from cloned cDNAs demonstrate that it encodes a
      structurally atypical Na channel isoform. We have prepared a cDNA probe specific
      for a portion of subunit domain IV of the glial channel and mapped the location
      of the corresponding gene (Scn7a) to mouse chromosome 2. The Scn7a gene mapped
      0.9 (+/- 0.9) cM distal to the Gcg locus; the location of the corresponding human
      gene (SCN7A) is predicted to be in the q36-q37 region of chromosome 2. This site
      lies just outside a cluster of genes for the brain-specific Na channel isoforms
      RI, RII and RIII which map proximal to Gcg (17). The presence of at least four
      genes from two distinct Na channel subfamilies suggests that multiple genetic
      defects for central and peripheral nervous system disorders ultimately may be
      linked to this area.

PMID- 8250914
TI  - A conserved 8 bp motif (GCYATCAY) in the 3'UTR of transition protein 2 as a
      putative target for a transcript stabilizing protein factor.
AB  - The 3'UTR of the transition protein 2 gene of several mammalian species was
      sequenced and the transcript level of this gene was determined by Northern blots.
      In all species tested so far, a Northern blot detectable transcript level was
      associated with the presence of a conserved 8 bp motif (GCYATCAY) 50 bp
      downstream of the stop codon. RNA-bandshift experiments indicate that this region
      is capable of binding a cytosolic protein factor from rat testis. These findings
      support our hypothesis that the low transcript level of the transition protein 2
      gene in human is due to insufficient storage of the mRNA as ribonucleic/protein
      particle.

PMID- 8250915
TI  - Atrial natriuretic peptide attracts human spermatozoa in vitro.
AB  - Here we report that atrial natriuretic peptide (ANP), a known activator of
      particulate guanylate cyclase, induces attraction and swimming speed enhancement
      of human spermatozoa in vitro. Using capillary assays under a variety of
      experimental conditions (ascending or descending gradients of ANP, or no gradient
      at all) and microscopic assays in which individual spermatozoa could be followed,
      we found that spermatozoa followed the gradient of ANP and accumulated in it.
      Speed enhancement was detected in the presence of ANP without a gradient. These
      observations suggest either that an ANP-like substance is the physiological
      attractant for human spermatozoa, or, more likely, that ANP directly affects
      guanylate cyclase in a manner similar to that caused by the physiological
      attractant.

PMID- 8250916
TI  - Cerebellar astrocytes specifically support the survival of Purkinje cells in
      culture.
AB  - As a first step toward identifying the factor(s) that is/are produced by
      astrocytes and support(s) the survival of cerebellar Purkinje cells in
      dissociated culture, we compared the effect of astrocytes of cerebellar,
      hippocampal, and cerebral origin. A feeder coverslip of cerebellar astrocytes,
      which did not have cell-to-cell contact to neuronal culture, increased the
      percentage of Purkinje cells to about 8-9 fold with no change in the percentage
      of astrocytes. On the other hand, astrocytes of hippocampal or cerebral origin
      did not increase the percentage of Purkinje cells at low plating density, whereas
      they increased the number of astrocytes in neuronal culture. These results
      indicate that the factor(s), tentatively named as Purkinje-cell survival factor
      was/were specifically produced by cerebellar astrocytes and affected directly on
      Purkinje cells.

PMID- 8250917
TI  - Neutrophil proteases associated with amyloid fibrils.
AB  - We found significant amounts of enzymatic activity characteristic of the human
      neutrophil proteases, elastase and cathepsin G, associated with isolated amyloid
      fibrils from patients with five different types of systemic amyloidosis. Amyloid
      deposits in tissue sections from the patients with amyloid A, amyloid
      transthyretin and amyloid beta 2-microglobulin amyloidosis also stained positive
      with antiserum to elastase and cathepsin G. Elastase and cathepsin G, found in
      the azurophilic granules of the neutrophil and, to a lesser extent, the monocyte,
      may become associated with amyloid precursor proteins before or during the
      formation of amyloid fibrils. This may occur in an extracellular inflammatory
      microenvironment or in a phagolysosome and play a role in the formation of the
      fibrils.

PMID- 8250918
TI  - Splicing of an anti-sense Alu sequence generates a coding sequence variant for
      the alpha-3 subunit of a neuronal acetylcholine receptor.
AB  - In this report we demonstrate that an alpha-3 acetylcholine receptor subunit
      transcriptional variant originates through alternative splicing of a
      complementary sequence of the right arm of an Alu element. This element is
      located within the 5.1 Kb intron found between exons 5 and 6 of the alpha-3
      acetylcholine receptor subunit gene. The transcriptional variant originates from
      the normal splicing process and carries an in-frame stop codon. If translated, it
      should encode for a peptide lacking the 4th transmembrane domain of the normal
      subunit.

PMID- 8250919
TI  - Common structural and expressional properties of vertebrate caldesmon genes.
AB  - We have determined the genomic structure of chicken caldesmon (CaD) gene. The
      gene, 100-150 kilobases long, is composed of 17 exons. Exons 1a-1, 1a-2, and 1a-3
      encode the 5'-terminal sequence specific to the mRNAs for CaDs expressed in
      gizzard. Exon 1b encodes the 5'-terminal sequence of the brain l-CaD and locates
      downstream of exons 1a-1, 1a-2, and 1a-3. The genomic construction of the chicken
      CaD resembles with that of the human CaD. Exon 3 of chicken CaD gene possesses
      the unique structure similar to that of human CaD gene; the common domain in both
      h- and l-CaDs (amino acid residues 74-199 for h-CaD and residues 66-191 for l
      CaD) and the central repeating domain specific to h-CaD (amino acid residues 200
      419) are encoded in exons 3a and 3b, respectively. Of particular interest is that
      the two consensus 5'-splice sites are found in the borders between exons 3a and
      3b, and exon 3b and intron. Therefore, the expressional regulation between h- and
      l-CaDs can be explained by selection of these 5'-splice sites. Alternative 3'
      splice sites also exist at intron/exon junction of exon 14 and the difference in
      selection of the sites would induce the specific Ala-508 insertion in the brain l
      CaD.

PMID- 8250920
TI  - Cloning and tissue distribution of subunits C, D, and E of the human vacuolar
      H(+)-ATPase.
AB  - The vacuolar proton ATPase (V-ATPase) translocates protons into intracellular
      organelles or across the plasma membrane of specialised cells such as osteoclast
      and renal intercalated cells. The catalytic site of the V-ATPase consists of a
      hexamer of three A subunits and three B subunits which bind and hydrolyse ATP and
      are regulated by accessory subunits C, D and E. cDNAs encoding subunits C, D, and
      E were cloned from human osteoclastoma, a tissue highly enriched in osteoclasts,
      as a first step in the characterisation of the V-ATPase used by the osteoclast.
      By Northern blot analysis only one mRNA species were detected for each of these
      subunits, which is consistent the constant transcription level in all tissues
      irrespective of the presence of specialised cells highly enriched in V-ATPases.

PMID- 8250922
TI  - Functional characterization of the cloned human ACTH receptor: impaired
      responsiveness of a mutant receptor in familial glucocorticoid deficiency.
AB  - The putative ACTH receptor gene has been identified on the basis of its tissue
      specific expression, structure, and limited expression data. We have expressed
      this gene in COS-7 cells and measured cAMP production in response to ACTH. An
      EC50 of 5.5 x 10(-9) M for ACTH (1-24) was determined. The S74I mutant ACTH
      receptor gene that associates with the syndrome of familial glucocorticoid
      deficiency had an EC50 of 67 x 10(-9) M. This discrepancy is consistent with the
      clinical data, and supports the hypothesis that this point mutation could account
      for the syndrome.

PMID- 8250921
TI  - Human elongation factor EF-1 beta: cloning and characterization of the EF1 beta
      5a gene and assignment of EF-1 beta isoforms to chromosomes 2,5,15 and X.
AB  - We report here the isolation and characterization of a novel human elongation
      factor-1 beta (EF-1 beta) gene by cDNA selection from YAC mapping on chromosome
      5q12-q14. This gene is specifically transcribed in fetal brain and in skeletal
      muscle and is characterized by a complete sequence homology with previously
      described EF-1 beta cDNAs. We also assigned the loci for three other EF-1 beta
      isoforms, to human chromosomes 2, 15 and X. The multiple chromosomal assignments
      of EF-1 beta loci demonstrates the genetic heterogeneity of human EF-1 beta
      peptides.

PMID- 8250923
TI  - The first demonstration of a procaryotic glycosylasparaginase.
AB  - Glycosylasparaginase was purified to near homogeneity from intracellular lysates
      of Flavobacterium meningosepticum. The enzyme is a heterodimer with an estimated
      molecular weight of 38 kDa and consists of one alpha-subunit (18 kDa) and one
      beta-subunit (16 kDa). The beta-subunit of the Flavobacterium enzyme has a direct
      evolutionary relationship to the beta-subunit of mammalian glycosylasparaginases
      as evidenced by: (1) strong cross-reactivity with antibodies made to the
      denatured rat beta-subunit, (2) a high degree of homology with the amino-terminus
      of the corresponding eukaryotic enzymes, and (3) irreversible inactivation with 5
      diazo-4-oxo-L-norvaline, a reagent known to react with the catalytic amino
      terminal threonine residue on the beta-subunit of a mammalian
      glycosylasparaginase.

PMID- 8250924
TI  - Effect of base-mismatch in the cohesive ends of oligonucleotide in gene cloning.
AB  - The tolerance of mismatched nucleotides between the cohesive ends of insert and
      target DNAs in gene cloning has been investigated. An oligonucleotide duplex with
      a cohesive end GGCC-5' or variation was ligated to the 5'-CCGG end of a
      linearized plasmid. The ligation mixture was used in the transformation of E.
      coli. A single-base mismatch, such as 5'-CCGG/AGCC-, GACC-, GGAC- or GGCA-5'
      (mismatch underlined), was well tolerated in the cloning of the oligonucleotide
      duplex, with efficiency lower than the fully complementary ends. Double-base
      mismatch 5'-CCGG/AACC- or GGAA-5' resulted in further decrease of cloning
      efficiency. Via a similar approach, a tetracycline resistance gene was
      successfully inserted into a pUC-type plasmid.

PMID- 8250925
TI  - Nitrite production by stimulated human polymorphonuclear leukocytes supplemented
      with azide and catalase.
AB  - The formation of nitric oxide by human phagocytes as measured by nitrite
      production is controversial. We report here that nitrite production by phorbol
      myristate acetate (PMA)-stimulated human polymorphonuclear leukocytes (PMN) is
      considerably increased by the addition of azide and a further increase occurs
      when catalase also is added. Nitrite production by the PMN-PMA-azide-catalase
      system is unaffected by superoxide dismutase or monomethylarginine but is
      markedly reduced by the substitution of chronic granulomatous disease for normal
      neutrophils. The stimulated neutrophils could be replaced by the H2O2-generating
      enzyme system glucose-glucose oxidase. These findings suggest that nitrite
      production does not, in this instance, reflect nitric oxide synthase activity by
      human neutrophils but rather the catalase-catalyzed conversion of azide to
      nitrite in the presence of H2O2 generated by the stimulated PMN.

PMID- 8250926
TI  - Spontaneous immortalization of mouse fibroblasts involves structural changes in
      senescence inducing protein, mortalin.
AB  - Mortalin, a novel member of mouse heat shock protein 70 (hsp70) family, is seen
      to distinguish the cellular mortal and immortal phenotypes by virtue of its
      cytosolic and perinuclear distribution, respectively. We report here that the
      cytosolic and perinuclear forms of mortalin from CD1-ICR mouse embryonic
      fibroblasts and NIH 3T3 cells, respectively, differ by two amino acids, can be
      distinguished on two-dimensional SDS-polyacrylamide gel. The perinuclear
      mortalins from RS-4 and Balb/c 3T3 cells harbor the same two amino acids as that
      of NIH 3T3 cells. However, these when analyzed with C-MEF mortalin did not
      exhibit the mobility shift equivalent to C-MEF and NIH 3T3 mortalins. The data
      indicate that the perinuclear mortalin from different immortal fibroblasts are
      not identical and implicate the possibility of additional structural changes in
      mortalin during immortalization. Such differences may also contribute to the
      differential in vitro growth characteristics of these immortal cells.

PMID- 8250927
TI  - Dynamics of exocytosis, endocytosis and recycling in single pituitary
      gonadotropes.
AB  - The dynamic changes in exocytosis, endocytosis and recycling in single
      gonadotropes induced by gonadotropin-releasing hormone (GnRH) were visualized and
      estimated with an impermeable fluorescent membrane probe, 1-(4
      trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatrien (TMA-DPH), using a digital
      imaging and confocal laser scanning microscope. 10(-7) M GnRH induced exocytosis
      and endocytosis within 10 sec and 60 sec, respectively. Recycling of the plasma
      membrane started at 180-300 sec. Exocytosis and endocytosis in purified
      gonadotropes changed dose-dependently with 10(-10)-10(-7) M GnRH. These results
      show that GnRH-induced exocytosis, endocytosis and recycling in gonadotropes
      maintain dynamic equivalence. The procedure we established will be very useful in
      studies of the function of secretory cells.

PMID- 8250928
TI  - Purification and characterization of two membrane bound serine proteinases from
      rat liver microsomes active in degradation of cytochrome P450.
AB  - Two serine proteinases capable of digesting cytochrome P4502E1 (CYP2E1) have been
      purified from sodium cholate solubilized rat liver microsomal membranes. After
      chromatography on hydroxyapatite, DEAE-Sepharose chromatography resolved the
      CYP2E1-degrading activity into two peaks, and the two proteinases were finally
      purified on benzamidine-Sepharose. Both have a M(r) of 32,000 on SDS-PAGE, are
      optimally active at pH 8, and show a susceptibility to inhibitors typical of
      serine proteinases. CYP2E1 degradation patterns exhibited by the proteinases are
      identical to each other and similar to that observed during the proteolysis of
      endogenous CYP2E1 in the microsomal membranes, which indicates that the
      proteinases can degrade CYP2E1 in its native environment. We suggest a role of
      these proteinases in the rapid phase of cytochrome P450 degradation in the
      endoplasmic reticulum.

PMID- 8250929
TI  - Inhibition of adenosine mediated responses in isolated hepatocytes by
      depolarizing concentrations of K+.
AB  - Isolated rat hepatocytes, incubated in a high K+ medium which depolarizes their
      plasma membrane, were used to investigate the response to adenosine. High K+
      concentration blocked both the adenosine mediated increase of calcium influx and
      the increase in the rate of urea synthesis. It is concluded that a) adenosine
      stimulates calcium influx in hepatocytes probably through receptor-operated Ca2+
      channels which are closed by depolarization of the plasma membrane, b) the higher
      cytosolic calcium concentration triggers a regulatory step that fully stimulates
      the rate in urea synthesis.

PMID- 8250930
TI  - Cloning of a cDNA for heat-shock protein hsp40, a human homologue of bacterial
      DnaJ.
AB  - We here isolated and characterized a cDNA clone encoding 40-kDa heat-shock
      protein hsp40 from cDNA expression library of human placenta by immunoscreening
      with anti-hsp40 antibody. N-terminal amino acid sequence (48 residues) deduced
      from the base sequence was completely identical to that of hsp40 purified from
      HeLa cells. Deduced amino acid sequence of the cDNA is homologous to bacterial
      DnaJ heat-shock protein and its homologues in yeast such as SCJ1, YDJ1(MAS5),
      SIS1, SEC63 and Zuotin. Nucleotide sequence identity between hsp40 and HDJ1
      (another human DnaJ homologue) is more than 98%, suggesting that these two
      proteins are the same gene product.

PMID- 8250931
TI  - Amelogenin post-translational modifications: carboxy-terminal processing and the
      phosphorylation of bovine and porcine "TRAP" and "LRAP" amelogenins.
AB  - TRAP and LRAP amelogenin components were isolated by size-exclusion and reversed
      phase HPLC from developing dental enamel. Porcine developing enamel contains TRAP
      and LRAP components analogous to those of bovine. Amino acid composition and mass
      spectrographic analyses established that, in both species, the carboxy-terminal
      sequences of the LRAP components are two residues longer than previously reported
      for bovine LRAP, and that both the TRAPs and LRAPs contained a single
      phosphorylated residue. These amelogenin polypeptides were the principal
      components of the enamel protein lower molecular weight fraction. The LRAP
      sequence data for both species suggests that the mechanism of amelogenin carboxy
      terminal processing may differ significantly from that previously suggested.

PMID- 8250932
TI  - Shear stress increases heparin-binding epidermal growth factor-like growth factor
      mRNA levels in human vascular endothelial cells.
AB  - Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently
      identified potent vascular smooth muscle cell (SMC) mitogen. We investigated the
      effect of shear stress on human HB-EGF mRNA levels in cultured human umbilical
      vein endothelial cells (HUVEC). In response to shear stress (8 dyne/cm2), HB-EGF
      mRNA levels in HUVEC increased rapidly, peaked at 3 h, and returned to near base
      line at 7 h. The shear stress-induced HB-EGF gene expression in HUVEC is
      completely blocked by 12-O-tetra-decanoylphorbol-13-acetate pre-treatment,
      suggesting the induction of HB-EGF is mediated by protein kinase C.

PMID- 8250933
TI  - Cloning and expression of the EP2 subtype of human receptors for prostaglandin
      E2.
AB  - Prostaglandin E2 (PGE2) is a potent mediator in many human tissues, that is
      recognized by three distinct subtypes of receptors, designated EP1, EP2 and EP3.
      A cDNA from a human lung library encodes a 53 kDa protein of 88% homology with
      the mouse EP2 receptor. Human EP2 receptors in COS-7 cell transfectants bound
      [3H]-PGE2 with a mean Kd of 2.2 nM and native specificity, and transduced
      increases in the intra-cellular concentration of cyclic AMP, but not of Ca++.
      That most EP2 receptor mRNA is in lung, kidney, intestinal, glandular and immune
      tissues, is consistent with functional responses.

PMID- 8250934
TI  - Isolation and characterization of a human liver cDNA as a candidate gene for
      Wilson disease.
AB  - The putative copper and ATP-binding domains of the human Menkes disease gene were
      used as probes to screen a human liver cDNA library at reduced stringency. Sixty
      five clones which remained positive after tertiary screening were subcloned and
      sequenced. One of these cDNA clones contains an open reading frame with 65% amino
      acid homology to the Menkes protein. Southern blot analysis localizes this cDNA
      to the region of the Wilson disease locus on chromosome 13. This cDNA detects a
      7.5 kB transcript which is present in human liver and cell lines devoid of the
      Menkes transcript and which is absent in liver from a patient with Wilson
      disease. These data suggest that this cDNA is a candidate gene for Wilson disease
      and that the protein encoded at this locus is a member of the P-type ATPase
      family.

PMID- 8250935
TI  - Regulation of c-MYC protein expression in the developing rat cerebellum by
      phosphoinositide turnover.
AB  - Using developing rat cerebellum, we examined the correlation between the turnover
      of phosphoinositide (PI) and c-myc expression. The 32P incorporation into
      polyphosphoinositides changed remarkably with advancing age. It reached a maximum
      value on PND 7, and then decreased gradually until PND 14. Immunostaining by anti
      PIP2 antibody changed in parallel. The expression of c-myc mRNA was also changed
      developmentally, showing a peak on PND 7; whereas c-MYC protein expression showed
      a peak on PND 10. Together, these results suggest that c-myc expression is
      regulated by PI turnover during the early developing stage of rat cerebellum.

PMID- 8250936
TI  - Study of energy transfer in the antenna system isolated from Mastigocladus
      laminosus Cohn.
AB  - Phycobilisomes oriented in stretched polymer films exhibit anisotropy of
      absorption and fluorescence. Up to now it was not clear in which way, by the
      deformation of their shape or by orientation of undeformed phycobilisome disk,
      this anisotropy of chromophore absorption and emission is reached. The
      photographs of two different kind of phycobilisomes obtained from cyanobacteria
      Tolypothrix tenuis and Mastigocladus laminosus were taken using a fluorescence
      microscope. From these photographs follows that phycobilisomes form in polymer
      big clusters and that these clusters are deformed as a result of stretching. It
      shows that predominantly the interaction between phycobilisomes is responsible
      for their orientation. Probably in clusters most phycobilisomes are oriented with
      disk diameter along the direction of film stretching. The fluorescence decay
      curves were recorded for Mastigocladus laminosus phycobilisomes embedded in PVA
      films. At least biexponential decay law has to be assumed. Calculated lifetimes
      are discussed in terms of energy transfer from primarily excited to fluorescent
      chromophores.

PMID- 8250937
TI  - Reduction of immunoreactivity of bovine serum albumin conjugated with comb-shaped
      polyethylene glycol derivatives.
AB  - Bovine serum albumin (BSA) was chemically modified with two types of comb-shaped
      copolymers of polyethylene glycol derivative and maleic anhydride, one with the
      molecular weight of 13,000 (activated PM13) and the other with 100,000 (activated
      PM100), to form PM13- and PM100-BSA. The immunoreactivity of BSA was markedly
      reduced by coupling with each modifier and was completely lost when 30% or 20% of
      amino groups in BSA were modified with activated PM13 or PM100, respectively. The
      esterase activity of PM13- and PM100-BSA without immunoreactivity were retained
      63% and 93% of non-modified one, respectively. These results were discussed with
      those of modified-asparaginases(1).

PMID- 8250938
TI  - Phospholipase A2 activation influences the processing and secretion of the
      amyloid precursor protein.
AB  - The phospholipase A2 (PLA2) inhibitors quinacrine, manoalide and scalaradial
      inhibit the carbachol-stimulated secretion of the amyloid precursor protein (APP)
      from cells transfected with the human m1 muscarinic receptor. Conversely,
      activation of PLA2 by melittin increases secretion of an apparently immature
      species of APP from these cells. These results implicate PLA2 in regulating APP
      processing and secretion, which may have important implications for understanding
      the pathogenesis of Alzheimer's Disease.

PMID- 8250939
TI  - Five palmitoylated polypeptides in the 50 KDa range are not recognized by an
      antibody against ribulose-biphosphate-carboxylase-oxygenase in Chlamydomonas
      reinhardtii.
AB  - After incubation of Chlamydomonas reinhardtii cells with radioactive palmitic
      acid several labelled bands appeared after gel electrophoresis of delipidated
      protein extract. Among them, two bands (a major and a minor one) were detected in
      the 50 KDa range, which is the region where the LSU of the Rubisco (large sub
      unit of the ribulose-biphosphate-carboxylase-oxygenase) was also found. Careful
      analyses by two-dimensional gel electrophoresis have shown that the five
      palmitate-labelled polypeptides detected in this region do not match with
      polypeptides immunoreacting with antibody against Rubisco. In addition,
      polypeptides labelled by palmitate cannot be immunoprecipitated with the same
      antibody further demonstrating that, in C. reinhardtii, the large sub-unit of
      Rubisco is not palmitoylated but unindentified proteins.

PMID- 8250940
TI  - Effects of omeprazole on gastric mucosal growth and differentiation in developing
      rat.
AB  - The effects of omeprazole on developing rat stomach mucosa were investigated.
      Infant rats were given subcutaneous injections of either omeprazole (25 mg/kg
      body weight/day) or vehicle once a day from the day after birth. As a result,
      omeprazole caused an elevation of mucosal pH and suppressed an increase in
      mucosal pepsinogen and its mRNA levels during stomach development.
      Histologically, these changes were associated with a reduction in mature
      pepsinogen-producing cells throughout stomach mucosa. Omeprazole also caused a
      delay in the expression of cathepsin E in surface mucous cells and an increase in
      labeled cells with bromodeoxyuridine. Thus, the present results indicate that
      omeprazole induces an increase in mucosal cell proliferation and delays the
      differentiation of developing rat stomach mucosa. Since the observed changes were
      remarkable especially from days 15 to 21 after birth when significant development
      of acid secretion occurs, the effects of omeprazole appear to be related with the
      potent acid inhibitory effect of the reagent.

PMID- 8250941
TI  - Increased release of KC/gro protein, intercrine cytokine family, from hepatocytes
      of the chronically ethanol fed rats.
AB  - In an attempt to clarify the mechanisms of neutrophil-accumulation in the liver
      of alcoholics, release of KC/gro protein (intercrine cytokine family) from
      hepatocytes in the chronically ethanol fed rats was examined. Chemotactic
      activity for rat neutrophils was demonstrated in the culture supernatant of
      hepatocytes isolated from the ethanol fed rats, which was then inhibited in the
      presence of antibody against rat KC/gro protein. Immunoblot analysis revealed
      that the peptide reacted with antiserum against KC/gro protein was demonstrated
      at a molecular weight of 20-23kDa, and an amount of KC/gro protein released from
      the hepatocytes of the chronically ethanol fed rats was increased, as compared
      with that of the control rats.

PMID- 8250942
TI  - Distribution of C-type natriuretic peptide and its messenger RNA in rat central
      nervous system and peripheral tissue.
AB  - In rat, the highest concentration of immunoreactive (ir-) C-type natriuretic
      peptide (CNP) was found in the central nervous system, as is the case in pig and
      human. Although its concentration in peripheral tissue was much lower than that
      in brain, CNP was present mainly as CNP-53 in ileum-jejunum, colon-cecum,
      stomach, kidney, lung, testis and submaxillary gland, but not in heart. By
      Northern blot analysis, CNP mRNA was detected in ileum-jejunum, testis, thymus,
      adrenal gland and submaxillary gland as well as in brain and spinal cord. CNP
      mRNA was further verified by reverse transcription-polymerase chain reaction to
      be present in most peripheral tissue, including aorta and bone marrow. These
      results indicate that CNP is synthesized in peripheral tissue and possibly
      functions as a local regulator in addition to acting as a neuropeptide in the
      central nervous system.

PMID- 8250943
TI  - Properties of a DNA-binding protein from rat nuclear scaffold fraction.
AB  - Our previous work [Hibino et al. (1992) Biochem. Biophys. Res. Commun. 184, 853
      858] has shown that a highly repetitive component in rat nuclear DNA forms a
      sequence-directed bend to have the binding affinity for the nuclear scaffold
      protein, P130. In the present experiment, the mobility shift DNA-binding assay
      suggested that the formation of the repetitive component-P130 complex is based on
      some cooperative mode of interaction. The DNase I footprint analysis revealed
      that the major binding region of this protein in the DNA is located near the
      center of the 370-bp XmnI repeat which has a strongly bent overall structure.
      These results imply that a nuclear scaffold protein such as P130 binds to
      sequence-directed bend(s) in a highly repetitive DNA to play an important role in
      construction of a higher-order chromatin structure.

PMID- 8250944
TI  - Enhancing factor, a Paneth cell specific protein from mouse small intestines:
      predicted amino acid sequence from RT-PCR amplified cDNA and its expression.

PMID- 8250945
TI  - A new method for the cytofluorimetric analysis of mitochondrial membrane
      potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro
      1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1).
AB  - A new method for the cytofluorimetric analysis of mitochondrial membrane
      potential in intact cells has been developed by using the lipophilic cationic
      probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide
      (JC-1), whose monomer emits at 527 nm after excitation at 490 nm. Depending on
      the membrane potential, JC-1 is able of forming J-aggregates that are associated
      with a large shift in emission (590 nm). The color of the dye changes reversibly
      from green to greenish orange as the mitochondrial membrane becomes more
      polarized. In two human cell lines (K562 and U937), we have studied by flow
      cytometry the changes in membrane potential provoked by the K+ ionophor
      valinomycin, a drug known to affect mitochondrial membrane potential, while the
      K+/H+ ionophor nigericin, known to affect intracellular pH but not mitochondrial
      membrane potential, was used as control. The incubation with valinomycin for 10
      min. at 37 degrees C in a low K+ medium provoked a marked and dose-dependent
      reduction in JC-1 greenish orange fluorescence, while nigericin had no effect.

PMID- 8250946
TI  - Rice membranes contain a calcium-dependent protein kinase activity with
      biochemical features of animal protein kinase C.
AB  - The presence of calcium-dependent protein kinase activities in rice was
      investigated. Membrane preparations could phosphorylate the MARCKS peptide, a
      highly specific substrate for animal protein kinase C (PKC). Phosphorylation,
      strictly dependent on calcium, was specifically antagonized by a peptide whose
      amino acid sequence corresponds to the inhibitory, pseudosubstrate domain of
      mammalian PKC. Similar results have been obtained with rice soluble fractions.
      Addition of inhibitors of mammalian PKC (staurosporine and calphostin C) also
      inhibited phosphorylation of specific peptide substrates. Western blot analysis
      with anti-PKC antibodies identified three major bands (90, 87 and 54 kD) in rice
      membrane-associated proteins.

PMID- 8250947
TI  - Protein-tyrosine kinase p72syk is activated by thromboxane A2 mimetic U44069 in
      platelets.
AB  - We show that p72syk is rapidly activated following the stimulation of thromboxane
      A2 mimetics, U44069 and STA2 in porcine platelets. The activity of p72syk reached
      a maximum at 10 s and decreased to a basal level within 60 s after 1 microM
      U44069 stimulation. This activation was enhanced in a dose-dependent manner and
      completely canceled by the pretreatment of platelet suspension with ONO3708, a
      specific antagonist of thromboxane A2. Pretreatment of platelets with aspirin as
      well as apyrase did not affect the activation of p72syk. When both extra- and
      intra-cellular Ca2+ were depleted, the activation of p72syk was still persistent;
      in contrast, the deactivation process was completely abrogated even at 120 s
      after U44069 stimulation. These results suggest that p72syk is a responsible
      enzyme to the protein-tyrosine phosphorylation events, and that p72syk functions
      mainly before Ca2+ recruitment in thromboxane A2-stimulated platelets.

PMID- 8250948
TI  - Human hexokinase II: sequence and homology to other hexokinases.
AB  - The amino acid sequence of human hexokinase II was deduced from the sequence of
      cDNA clones isolated from a skeletal muscle library. An open reading frame of
      2751 bases encodes a protein of 917 amino acids. The deduced amino acid sequence
      has 94% identity with rat hexokinase II but only 72% identity with human
      hexokinase type I. In addition to hexokinase II clones, the human skeletal muscle
      cDNA library contained at least an equal number of clones of hexokinase I, the
      isoform reported to be typically found in kidney and brain. Genetic variation in
      hexokinase II could underlie insulin resistance in peripheral tissues and cause
      non-insulin-dependent diabetes mellitus. The availability of this sequence would
      facilitate investigating the role of mutations in the HKII gene in the etiology
      of this disease.

PMID- 8250949
TI  - Detection of phosphodiester resonances in the perfused heart from vertebrate
      ectotherms with nuclear magnetic resonance.
AB  - In vivo 31P NMR has been used to characterize the phosphorylated compounds
      present in the heart from vertebrate ectotherms. The perfused hearts from all
      animals experimented showed prominent resonances between the inorganic phosphate
      and phosphocreatine peaks. The pattern of these compounds was found to be
      different in the heart of the different species. As shown by 31P and proton NMR
      of perchloric extracts, the chemical shift of some of the compounds was
      characteristic of glycerophosphorylcholine, glycerophosphorylinositol,
      phosphorylcholine, phosphorylserine, phosphorylethanolamine and
      phosphoenolpyruvate. The non-identified resonances were found to be
      phosphodiesters, as demonstrated by alkaline phosphatase hydrolysis. The
      physiological significance of these high levels of phosphodiesters in the heart
      from vertebrate ectotherms is discussed.

PMID- 8250950
TI  - Salmon calcitonin binding and stimulation of cyclic AMP generation in rat
      skeletal muscle.
AB  - Salmon calcitonin potently competes for amylin binding sites in rat brain and has
      amylin-like actions upon glucose metabolism in rat muscle. We report here that
      [125I]-salmon calcitonin binds to rat hindlimb muscle membranes with high
      affinity (Kd = 0.47 pM). Binding was inhibited by rat amylin (Ki = 2 nM), rat
      alpha CGRP (Ki = 8 nM), rat beta CGRP (Ki = 11 nM), and rat calcitonin (Ki = 64
      nM). Binding was maximal when measured in a hypotonic NaHepes buffer, and was
      significantly reduced in affinity when salts of Mg++, Ca++, Na+ or K+ were
      present. Incubation of rat hindlimb muscle membranes with salmon calcitonin at
      concentrations of 10 pM and above stimulated cyclic AMP generation. These results
      describe a skeletal muscle binding site which may mediate some of the actions of
      exogenous salmon calcitonin and of endogenous amylin and related peptides upon
      skeletal muscle fuel metabolism.

PMID- 8250951
TI  - High magnesium concentration inhibits ligand-stimulated calcium influx and
      hormone secretion in rat pituitary lactotropes with involvement of intracellular
      free magnesium.
AB  - The effects of extracellular magnesium concentration ([Mg2+]ex) on thyrotropin
      releasing hormone (TRH)-stimulated intracellular free calcium mobilization and
      prolactin secretion were investigated concomitantly with measurement of the
      intracellular free magnesium concentration ([Mg2+]i). TRH-stimulated
      intracellular free calcium mobilization was significantly inhibited when the
      medium was replaced by high Mg2+ medium ([Mg2+]ex = 10 mM) in normal Ca2+ medium.
      The inhibitory effects of high Mg2+ became apparent concomitantly with an
      increase in [Mg2+]i from 0.7 to 1.3 mM. High Mg2+ significantly inhibited TRH
      induced PRL secretion in a dose-dependent manner in normal Ca2+ medium. TRH
      stimulated inositol triphosphate (IP3) production was rather augmented by the
      replacement with high Mg2+ medium. In summary, high Mg2+ inhibits Ca2+ influx
      stimulated by TRH in the rat pituitary lactotropes, possibly with the involvement
      of [Mg2+]i increase. These results have general importance in relation to high
      Mg(2+)-induced suppression of the biological functions of cells.

PMID- 8250952
TI  - Structural basis for the presumptive atherothrombogenic action of lipoprotein(a).
      Facts and speculations.

PMID- 8250953
TI  - Comparison of hamster and mouse reveals interspecies differences in the
      regulation of hepatic CYP2A isozymes.
AB  - Three CYP2A-related activities [coumarin 7-hydroxylase (COH), testosterone 7
      alpha- (test7 alpha) and 15 alpha-hydroxylases (test15 alpha)], identified in
      hamster liver and analysed by immunoinhibition, and western and northern
      blotting, were found to be similar to mouse and human CYP2As. In the microsomal
      fractions, anti-mouse CYP2A5 antibody recognised three bands of about 48, 49 and
      52 kDa, suggesting the presence of at least three proteins immunologically
      similar to mouse CYP2A5. The 49 kDa band migrated close to mouse CYP2A5 and
      changes in its expression followed COH and test15 alpha activities. Test7 alpha
      activity did not associate with any of the individual bands detected on western
      blots despite its strong inhibition by the antibody. Despite the immunological
      and catalytic similarities between mouse and hamster CYP2A enzymes, their
      regulation is different. In mice, the enzyme activities are higher in females
      than males, are induced by pyrazole (PY) and phenobarbital (Pb), and are not
      affected by 3-methylcholanthrene (MC). In hamsters, activities are not higher in
      females, induced by MC and reduced by PY. MC and PY appear to regulate expression
      at the mRNA level, while Pb seems to act post-transcriptionally by increasing
      either the synthesis or the stability of the protein. Our data indicate that the
      modes of expression and regulation of CYP2A-related enzymes make the hamster
      different from mice and humans with respect to the mechanism of metabolism of
      certain drugs and carcinogens.

PMID- 8250954
TI  - Dehydroepiandrosterone pretreatment protects rats against the pro-oxidant and
      necrogenic effects of carbon tetrachloride.
AB  - A single intraperitoneal injection of dehydroepiandrosterone (3 beta-hydroxy-5
      androsten-17-one, DHEA) 17 hr before carbon tetrachloride (CCl4) poisoning
      protects rats against liver injury induced by the haloalkane. In liver
      homogenates, both the increase in malondialdehyde production and the formation of
      fluorescent lipid peroxidation products are significantly reduced. Also, liver
      microsomes obtained from DHEA-pretreated rats incubated in vitro with CCl4 are
      less susceptible to lipid peroxidation than microsomes from normal animals. The
      release of liver enzymes into the blood is much reduced in DHEA-pretreated rats,
      confirming a cause-effect relationship between lipid peroxidation and hepatocyte
      death. Treatment with DHEA inhibits neither glucose-6-phosphate dehydrogenase
      activity in the cytosol, nor the microsomal mixed function oxidase system
      (cytochrome P450 content, aminopyrine demethylase and ethoxycoumarin de-ethylase
      activities). In animals treated with DHEA, the liver content of total glutathione
      and vitamin E is not modified. These results support the hypothesis that DHEA
      protects against CCl4-induced liver injury through its own antioxidant activity,
      rather than by interfering with the metabolism of the toxin or with the tissue
      level of primary antioxidants.

PMID- 8250955
TI  - Hydroxyl radical damage to DNA sugar and model membranes induced by anthralin
      (dithranol).
AB  - The antipsoriatic anthrones anthralin and butantrone caused degradation of the
      DNA sugar deoxyribose in the presence of ferric salt. The degradation was
      substantially inhibited by iron-binding hydroxyl radical scavengers, iron
      chelators, superoxide dismutase (SOD) and catalase, suggesting a mechanism in
      which antipsoriatic anthrones generate hydroxyl radicals via the Fenton reaction
      or an iron-catalysed Haber-Weiss reaction. Butantrone was markedly less efficient
      at generating hydroxyl radicals than anthralin. Using bovine brain phospholipid
      liposomes as model membranes to study the effects of antipsoriatic anthrones on
      lipid peroxidation, the peroxidation of liposomal membranes in the presence of
      ferric salt was maximally enhanced by anthralin and butantrone at 12.5 and 5
      microM, respectively. Higher concentrations of the drugs resulted in less
      peroxidation. Chain-breaking antioxidants and iron chelators strongly decreased
      anthralin-enhanced lipid peroxidation, suggesting the involvement of hydroxyl,
      peroxyl or alkoxyl radicals. In contrast to their stimulatory effects on
      liposomal membrane peroxidation, both anthralin and butantrone diminished
      Fe3+/ascorbate-induced lipid peroxidation in liposomes. Butantrone was more
      effective as an inhibitor of lipid peroxidation than was anthralin. The
      antioxidant properties of antipsoriatic anthrones were determined in terms of
      their reactivities with the stable free radical 2,2-diphenyl-1-picrylhydrazyl
      (DPPH). Antioxidant activity of antipsoriatic anthrones requires the presence of
      free hydroxyl groups at C-1 and C-8 and at least one hydrogen atom at C-10 of the
      anthrone nucleus. The role of active oxygen species produced by antipsoriatic
      anthrones and the biological effects on cellular targets are discussed with
      respect to the mode of action and manifestation of side effects of these drugs.

PMID- 8250956
TI  - Effect of alpha 1-acidglycoprotein on myocardial uptake and pharmacodynamics of
      quinidine in perfused rat heart.
AB  - The myocardial uptake and pharmacodynamics of quinidine were examined in the
      isolated perfused rat heart preparation under conditions of varying
      concentrations of bovine alpha 1-acidglycoprotein (AAG) in the perfusate. Three
      hearts were perfused for five consecutive 35 min phases with buffer containing
      quinidine and AAG in concentrations of 0, 0.1, 0.5, 1.5 and 0 g/L, in that order,
      with a 55 min washout period between each phase. The equilibration rate constant
      for the quinidine output concentration increased with increasing AAG
      concentration, but not as much as predicted by the conventional pharmacokinetic
      uptake model, which assumes constant capillary permeability among the phases.
      Estimates of the permeability surface product for the two zero AAG phases (17.7
      +/- 1.91 and 19.1 +/- 0.82 mL/min/g) were significantly greater than those for
      the three AAG phases (8.94 +/- 0.99, 8.70 +/- 0.26, 9.01 +/- 0.26 mL/min/g; P <
      0.05). This effect of AAG is the same as that observed previously by us with
      bovine serum albumin in this same experimental preparation. This suggests that
      the mechanism of reduced capillary permeability is the same for both proteins,
      i.e., the formation of a steric barrier to paracellular transport rather than an
      electrostatic barrier. There was a direct, linear relationship between
      lengthening of the QT interval of the electrocardiogram and total and unbound
      quinidine concentrations, but the relationship for unbound concentration was
      independent of quinidine unbound fraction. Therefore, the electrocardiogram
      effect of quinidine was directly related to the circulating unbound rather than
      total drug concentration.

PMID- 8250957
TI  - Common food additives are potent inhibitors of human liver 17 alpha
      ethinyloestradiol and dopamine sulphotransferases.
AB  - Interactions between dietary xenobiotics, drugs and biologically active
      endogenous compounds are a potential source of idiosyncratic adverse pathology.
      We have examined the inhibition of the sulphation of a number of xenobiotics and
      endobiotics in human liver cytosol by 15 food additives and constituents.
      Sulphation of dehydroepiandrosterone was resistant to inhibition by all compounds
      tested; however, dopamine sulphotransferase (ST) activity was inhibited strongly
      by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine and vanillin.
      Sulphation of the xenobiotic steroid 17 alpha-ethinyloestradiol (EE2) was
      inhibited by vanillin, erythrosin B and octyl gallate. Of these compounds, only
      vanillin was found to be sulphated to a significant extent by both human liver
      and platelets, and vanillin was determined to be a substrate for the monoamine
      sulphating isoenzyme of phenolsulphotransferase. Vanillin was found to inhibit
      50% of liver EE2 ST activity (IC50) at a concentration of approximately 1.3
      microM and the mode of inhibition was non-competitive. The implications of these
      results for the adverse side effects associated with food additives and oral
      contraceptives are discussed.

PMID- 8250958
TI  - Study of interaction of carprofen and its enantiomers with human serum albumin-
      II. Stereoselective site-to-site displacement of carprofen by ibuprofen.
AB  - The site-to-site displacement of carprofen, a site II-specific drug, bound to
      human serum albumin (HSA) by ibuprofen, another site II-specific drug, was
      qualitatively and quantitatively studied by circular dichroism (CD) and
      equilibrium dialysis (ED). Carprofen gives rise to different CD spectra at lower
      (1:1) and higher (3:1) molar ratios to HSA, indicating different mechanisms for
      the binding of this drug to its high and low affinity sites on HSA. Ibuprofen at
      a 5:1 molar ratio to HSA displaces carprofen at a molar ratio of 1:1 to HSA from
      its high affinity binding site (site II) to its low affinity site (site I), as
      shown by production of the CD spectrum similar to that obtained in the case of
      the carprofen-HSA complex at a molar ratio 3:1. As revealed by the ED
      experiments, the free fraction of carprofen at a molar ratio of 1:2 to HSA (2 x
      10(-5) M) was not initially increased by the addition of ibuprofen at a lower
      concentration, but at a higher concentration (6 x 10(-5) M), the free fraction
      was increased by only 90%. When site I was sufficiently blocked by a site I
      specific drug like warfarin or phenylbutazone (6 x 10(-5) M), there was about a 4
      fold increase in the free fraction of carprofen caused by ibuprofen. This site-to
      site displacement demonstrated by carprofen was found to be stereospecific as
      indicated by the highest interaction between the S(+)-enantiomers of carprofen
      and ibuprofen. Moreover, the displacement of carprofen occurred at the
      azapropazone region rather than the warfarin region of site I on HSA.

PMID- 8250959
TI  - Increase in liver microsomal glutathione S-transferase activity by phenobarbital
      treatment of rats. Possible involvement of oxidative activation via cytochrome
      P450.
AB  - The possible involvement of oxidative activation of liver microsomal glutathione
      (GSH) S-transferase by the cytochrome P450 system was investigated. When rats
      were given phenobarbital (PB) intraperitoneally for 3 days, liver microsomal GSH
      S-transferase activity was stimulated 1.3-1.4-fold and the effect of PB on the
      transferase was potentiated by combination with a catalase inhibitor, 3-amino
      1,2,4-triazole. Immunoblotting of microsomal proteins from PB-treated rats with
      anti-microsomal GSH S-transferase antibody after SDS-PAGE showed the presence of
      a dimer of the transferase. When microsomal suspensions prepared from PB-treated
      rats were placed on ice without GSH, the microsomal GSH S-transferase activity
      gradually increased with time and reached 200% of the initial level at 3 hr when
      activation of the transferase by N-ethylmaleimide was lost. The time-dependent
      increase in GSH S-transferase activity in PB-treated microsomes was prevented by
      addition of 0.1 mM GSH. The increase in microsomal GSH S-transferase activity by
      NADPH was depressed by cytochrome P450 inhibitors such as SKF 525-A (2
      diethylaminoethyl-2,2-diphenylvalerate), metyrapone or isoniazid in agreement
      with the concomitant decrease in generation of hydrogen peroxide in microsomes.
      These results indicate that the increase in GSH S-transferase activity in liver
      microsomes by PB treatment of rats is due to the oxidative modification of the
      enzyme by reactive oxygen species which are concomitantly increased following
      induction of cytochrome P450.

PMID- 8250960
TI  - Effects of anti-free radical interventions on phosphatidylcholine hydroperoxide
      in plasma after ischemia-reperfusion in the liver of rats.
AB  - The present study set out to investigate whether plasma phosphatidylcholine
      hydroperoxide (PCOOH) levels could accurately reflect lipid peroxidation linking
      to liver damage due to ischemia--reperfusion. PCOOH is a primary peroxidative
      product of phosphatidylcholine (PC), which is the most important functional lipid
      in the hepatocellular membrane, and may mediate oxidative stress. We quantified
      PCOOH and PC in the plasma and liver of rats subjected to hepatic ischemia
      reperfusion by chemiluminescence detecting HPLC (CL-HPLC) method. Plasma PCOOH
      levels showed no significant rise in either the ischemia only group or in the
      sham-operation group, compared to controls (0.7 nmol/mL plasma). At 60 min
      subsequent to reperfusion, the PCOOH levels in plasma and liver, as well as the
      levels of several serum markers of liver injury [lactic dehydrogenase (LDH),
      glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)]
      increased in proportion to the duration of ischemia (up to 60 min). During
      periods of reperfusion following 30 min of ischemia, plasma PCOOH increased
      biphasically (2 nmol/mL; 12-24 hr duration of reperfusion), and generally ran
      parallel to that in the liver after more than 60 min of reperfusion. Dose
      dependent protective effects against warm ischemia (30 min)-reperfusion (12 hr)
      injury were clearly demonstrated in the groups treated with allopurinol,
      diclofenac Na, ascorbic acid (V.C), alpha-tocopherol and coenzyme Q10, but not in
      those treated with r-h-superoxide dismutase or betamethasone. The rises in plasma
      PCOOH and serum GOT, GPT and LDH of the ischemia-reperfused rats were ameliorated
      most in the group pretreated with diclofenac Na, and next most in the group
      pretreated with V.C. These results indicate that the plasma PCOOH levels are a
      useful index both for liver cell damage induced by oxygen free radicals generated
      during ischemia-reperfusion, and to investigate the efficacy of drugs against
      oxidative stress.

PMID- 8250961
TI  - Substrate stereoselectivity and enantiomer/enantiomer interaction in propranolol
      metabolism in rat liver microsomes.
AB  - The substrate stereoselectivity and enantiomer/enantiomer interaction of (S)- and
      (R)- propranolol for the formation of their metabolites were investigated in rat
      liver microsomal fractions. The enantiomers of primary metabolites of
      propranolol, 4-, 5-, 7-hydroxy- and N-desisopropyl-propranolol were separated and
      assayed by an HPLC method employing a chiral ovomucoid column. Regioselective
      substrate stereoselectivity (R < S for 4- and 5-hydroxylations; R > S for 7
      hydroxylation; R = S for N-desisopropylation) was observed in the formation of
      propranolol metabolites when the individual enantiomers or a racemic mixture of
      propranolol were used as substrates. Concentration-dependent metabolic inhibition
      of propranolol enantiomers by their optical isomers was also observed. In
      addition, the inhibition of propranolol 4-, 5- and 7-hydroxylations between the
      enantiomers showed a typical competitive nature. These findings suggested that
      the propranolol enantiomers competed for the same enzyme, probably a cytochrome
      P450 isozyme in the CYP2D subfamily.

PMID- 8250962
TI  - Combination of reduced folates with methotrexate or 5-fluorouracil. Comparison
      between 5-formyltetrahydrofolate (folinic acid) and 5-methyltetrahydrofolate in
      vitro activities.
AB  - Folinic acid (dlFA) is increasingly used in clinical oncology. The active isomer
      lFA is intensively metabolized into l5-methyltetrahydrofolate (l5MTHF), the
      relative proportions of lFA, dFA and l5MTHF in blood varying considerably between
      oral and i.v. FA administration. The purpose of the study was to compare the in
      vitro activities of pure lFA and pure l5MTHF at equivalent drug exposure [area
      under curve (AUC)], taking into account their respective chemical stability in
      the culture medium. The in vitro growth inhibition [3-(4,5-dimethylthiazol-2-yl)
      2,5 diphenyltetrazolium bromide (MTT) test] was evaluated on five human tumor
      cell lines after methotrexate (MTX)-folate or 5-fluorouracil (5FU)-folate
      exposures. Not only were the activities of lFA and l5MTHF compared, but also
      clinically relevant mixtures of lFA + dFA + l5MTHF corresponding to the
      proportions found at steady state during oral (PO mixture, 4, 39 and 57%,
      respectively) and i.v. administrations (i.v. mixture, 7, 81 and 12%,
      respectively). Measurement of folates demonstrated the marked lability of l5MTHF
      (65.8% loss over 5 days in the culture medium) as compared to lFA (2.6% loss).
      Whatever the pharmacological model tested (MTX-folate or 5FU-folate), comparison
      of the folate effects at equivalent drug exposure taking into account their
      relative stability showed that l5MTHF was never more potent than lFA. Moreover, a
      higher efficiency of lFA was demonstrated for the cell line most sensitive to
      5FU; in this case, as expected, the i.v. mixture was more potent than the PO
      mixture. This study shows that depending on the tumor, lFA can be more potent
      than its main circulating metabolite l5MTHF. Along with the limited capacity of
      oral absorption, the choice between oral and i.v. route for FA administration in
      patients should take into consideration the different pharmacological activities
      between lFA and l5MTHF which suggest that the oral route is potentially
      detrimental to the optimal activity of the 5FU-FA combination as compared to i.v.
      administration.

PMID- 8250963
TI  - Stereoselectivity of human liver and intestinal cytosolic fractions as well as
      purified human glutathione S-transferase isoenzymes towards 2-bromoisovalerylurea
      enantiomers.
AB  - Glutathione (GSH) conjugation of 2-bromoisovalerylurea (BIU) enantiomers is
      stereoselective in humans in vivo. Administration of racemic BIU results in a
      higher plasma elimination and urinary excretion of R-BIU and its mercapturate,
      respectively, than of S-BIU and its mercapturate. In order to relate the in vivo
      BIU pharmacokinetics to the activity of glutathione S-transferase (GST)
      isoenzymes, the GSH conjugation of BIU enantiomers was studied with human liver
      and intestinal cytosolic fractions as well as purified human class alpha (GSTA1
      1, GSTA2-2), mu (GSTM1a-1a) and pi (GSTP1-1) GST isoenzymes. Stereoselective GSH
      conjugation of BIU enantiomers was observed for most human liver and intestinal
      cytosolic fraction. In general, the cytosolic fractions preferentially conjugated
      S-BIU. Stereoselective preference for GSH conjugation of S-BIU was also observed
      for GSTA2-2 and GSTM1a-1a, whereas GSTA1-1 was not selective for either of the
      BIU enantiomers. GSTP1-1 did not catalyse conjugation of R- and S-BIU.
      Quantification of the GST isoenzymes in the liver cytosolic fractions showed that
      the stereoselectivity towards S-BIU was related to the profile and amount of GST
      subunits in the cytosolic fractions. The discrepancy in stereoselectivity between
      the BIU pharmacokinetics in vivo and the GSH conjugation of BIU enantiomers in
      vitro is discussed. In addition, since in contrast to human GSTM1a-1a, rat class
      Mu isoenzymes prefer R-BIU, the present results indicate that related isoenzymes
      in different species may have a different stereoselectivity.

PMID- 8250964
TI  - Cytochrome P450 induction and metabolism of alkoxyresorufins, ethylmorphine and
      testosterone in cultured hepatocytes from goats, sheep and cattle.
AB  - Very little is known of cytochrome P450 (P450) patterns and enzyme
      characteristics in food-producing animal species. Oxidative metabolism of
      alkoxyresorufins, ethylmorphine (EtM) and testosterone (TST) was used to monitor
      the effects of the P450 inducers phenobarbital (PB), beta-naphthoflavone (BNF),
      dexamethasone (DEX) and triacetyloleandomycin (TAO) in primary cultured
      hepatocytes from goats, sheep and cattle. BNF effectively and specifically
      induced ethoxyresorufin deethylase (> 20-fold), indicating the presence of an
      inducible P450 1A form, and down-regulated EtM demethylation and most selected
      TST hydroxylations. In non-induced hepatocyte cultures, TST was metabolized to 6
      beta-, 2 beta-, 12 beta-, and 11 alpha-hydroxy-TST (OHT). PB and, to a lesser
      extent, DEX non-specifically induced all OHT formations, and EtM demethylation.
      TAO almost completely inhibited OHT formation and EtM demethylation. These
      results indicate the involvement of principally one P450 form, or a restricted
      number of related P450 forms, presumably belonging to the P450 3A subfamily. In
      western blot analysis, cross reactivity was found with rat anti-P450 3A1 and anti
      sheep P450 3A. A more specific PB effect was observed for 16 alpha-OHT, which may
      be formed though a ruminant P450 2B form. None of the inducers influenced
      pentoxyresorufin depentylase (PROD) or EtM O-deethylation. Metabolite patterns
      and inducibility of selected activities in ruminant hepatocytes are in accordance
      with previous findings in goats in vivo. Cytochrome P450 characteristics in
      ruminants appear to differ from those in rats whereas similarities to the
      situation in humans appear to exist.

PMID- 8250966
TI  - Theoretical considerations for the application of competitive polymerase chain
      reaction to the quantitation of a low abundance mRNA: estrogen receptor.
AB  - The necessary theoretical considerations for the development of a correct
      quantitative analysis of a low abundance messenger RNA (mRNA), estrogen receptor
      mRNA, by competitive polymerase chain reaction (PCR) are presented together with
      a series of experimental data. When compared to other methodologies currently
      utilized for RNA quantitation, this PCR application proved to be a very reliable,
      rapid and sensitive method. Furthermore, the PCR-based quantitative method
      described is of particular interest since it does not require the use of
      radiolabeled compounds.

PMID- 8250965
TI  - Fibrates modify rat hepatic fatty acid chain elongation and desaturation in
      vitro.
AB  - Three fibric acid derivatives, clofibric acid (CFB), bezafibrate (BFB), and
      gemfibrozil (GFB), mainly used in the treatment of hypertriglyceridaemic or mixed
      hyperlipidaemic states, have been tested for their ability to modify fatty acid
      chain elongation and desaturation in vitro. Both endogenous and exogenous
      (saturated, monounsaturated and polyunsaturated) fatty acid elongations were
      inhibited by fibrates at concentrations well within the physiological range (IC50
      values for GFB were between 0.1 and 0.3 mM). The potency order was GFB > BFB >
      CFB. Inhibition was not due to an impairment of the activation step from free
      fatty acids to acyl-CoAs, as palmitoyl-CoA synthetase was only slightly inhibited
      (IC50 value for GFB = 2.8 mM). Fibrates (GFB) appeared to behave as mixed non
      competitive inhibitors with respect to malonyl-CoA when the rate limiting step of
      elongation, the condensing enzyme, is assayed. Further, delta 6 and delta 5
      desaturates were inhibited by the three drugs (GFB > BFB > CFB), although not to
      the same extent as the elongation system. In contrast, delta 9 desaturase
      activity was not affected by fibrates.

PMID- 8250967
TI  - Further studies on the involvement of selenium in peroxisome proliferation in rat
      liver. Comparison of effects with clofibric acid and perfluorooctanoic acid and
      the pharmacokinetics of [14C]clofibrate.
AB  - Most effects of the peroxisome proliferator clofibrate on rat liver are marginal
      or absent in selenium (Se) deficiency. The purpose of the present study was to
      determine whether the uptake or distribution of clofibrate is altered by Se
      deficiency. Rats were fed a Se-adequate or -deficient diet for 10-11 weeks and
      then these same diets with 0.5% (w/w) clofibric acid (the direct acting
      hydrolysis product of clofibrate) or 0.02% (w/w) perfluorooctanoic acid (PFOA)
      for 10 days. Other groups of rats received radiolabeled clofibrate by intubation.
      Clofibric acid was an ineffective as clofibrate in producing effects (i.e.
      decreased body weight gain, increases in liver somatic index and protein content
      of the mitochondrial fraction, and increased activities of catalase and
      peroxisomal fatty acid beta-oxidation) in the liver of Se-deficient rats.
      Microsomal omega-hydroxylation was, however, equally induced in both dietary
      groups. In contrast to clofibric acid, the biological effects of PFOA were not
      affected by Se status. Furthermore, neither the tissue distribution (plasma,
      liver and kidney) nor the urinary excretion of 14C was affected by Se deficiency.
      These results demonstrate that the hydrolysis of clofibrate to clofibric acid is
      not impaired in the Se-deficient rat. In addition, the involvement of Se in the
      effects of peroxisome proliferators differs for different members of this
      structurally heterogeneous group of compounds. It is concluded that the Se
      deficient rat may provide valuable information concerning the biochemical
      mechanism(s) underlying peroxisome proliferation.

PMID- 8250968
TI  - Roles for oxidative stress and poly(ADP-ribosyl)ation in the killing of cultured
      hepatocytes by methyl methanesulfonate.
AB  - The mechanisms by which the methylating agent methyl methanesulfonate (MMS) kills
      cultured hepatocytes were studied. In an amino-acid-free Krebs-Ringer buffer
      (KRB), 1 mM MMS depleted the cells of glutathione (GSH) within 1-2 hr. Lipid
      peroxidation, as measured by the accumulation of malondialdehyde (MDA), followed,
      and over 70% of the cells died within 3-4 hr. The iron chelator deferoxamine and
      the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) prevented lipid
      peroxidation and death of the hepatocytes without any effect on the loss of GSH.
      3-Aminobenzamide (ABA), a poly(ADP-ribose) polymerase inhibitor, also prevented
      the cell killing by attenuating the loss of GSH. In a culture medium containing
      amino acids and antioxidants (Williams' E medium, WEM), 1 mM MMS killed the
      hepatocytes more slowly, with 70% of the cells dying 8-12 hr after treatment.
      Lipid peroxidation accompanied the loss of viability. Deferoxamine and DPPD
      inhibited lipid peroxidation, while only partially protecting against the cell
      killing. ABA offered more protection and reduced the decline of GSH and decreased
      lipid peroxidation. ABA also reduced the extent of the depletion of both NAD and
      ATP that accompanied the cell killing by MMS in WEM. These data indicate that MMS
      killed the hepatocytes by different mechanisms depending on the culture
      conditions. In KRB, the toxicity of MMS was a consequence of oxidative cell
      injury that follows the depletion of GSH. In WEM, both oxidative injury and the
      action of poly(ADP-ribose) polymerase in response to DNA single-strand breaks
      contributed to the loss of viability.

PMID- 8250969
TI  - Stimulation of calcium release by caffeine analogs in pheochromocytoma cells.
AB  - Caffeine (EC50 approximately 20 mM) causes a maximal 400% increase in
      intracellular calcium ion concentration ([Ca2+]i) in pheochromocytoma PC12 cells.
      A range of caffeine analogs in which methyl groups at the 1, 3, and 7 positions
      were replaced with relatively nonpolar (ethyl, allyl, propyl, propargyl) or polar
      (CH2COOH, CH2CH2OH, CH2CN, CH2OCH3) substituents were tested at a 10 mM
      concentration. Many analogs were as efficacious or only somewhat less efficacious
      than 10 mM caffeine. Certain analogs with polar substituents had no effect.
      Disubstituted xanthines were less efficacious (theophylline, paraxanthine) than
      caffeine or were ineffective (theobromine). 1-Propyl-3,7-dimethylxanthine (EC50 4
      mM) and 1-propargyl-3,7-dimethylxanthine (EC50 5 mM) were several-fold more
      potent than caffeine in causing elevation of [Ca2+]i and the latter was at least
      as efficacious.

PMID- 8250970
TI  - Alteration of the phosphorylation state of p34cdc2 kinase by the flavone L86-8275
      in breast carcinoma cells. Correlation with decreased H1 kinase activity.
AB  - The flavone L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3-hydroxy-1
      methyl)- piperidinyl]-4H-1-benzopyran-4-one] delayed the progression of
      aphidicolin-synchronized MDA-468 breast carcinoma cells through S phase and
      prevented progression through G2. L86-8275 prevented the G2-related increase in
      histone H1 kinase activity mediated by cyclin-dependent kinase-1 (p34cdc2
      kinase). L86-8275 inhibited [32P]orthophosphate labeling of p34cdc2 threonine and
      tyrosine residues and decreased the phosphotyrosine content of p34cdc2.
      Diminution of p34cdc2 phosphotyrosine appeared selective, as a general depletion
      of cellular phosphotyrosine was not observed. The mass of p34cdc2 in L86-8275
      exposed cells was not decreased during the period over which these effects
      occurred. [35S]Methionine labeling of p34cdc2 or other cellular proteins was not
      inhibited at concentrations that were effective for complete cellular growth
      inhibition. We hypothesize that L86-8275 interferes with the normal cell cycle
      dependent phosphorylation of p34cdc2, resulting in decreased kinase activity and
      cell cycle arrest.

PMID- 8250971
TI  - Structure-activity relationship of nucleobase ligands of uridine phosphorylase
      from Toxoplasma gondii.
AB  - Seventy-nine nucleobase analogs were evaluated as potential inhibitors of
      Toxoplasma gondii uridine phosphorylase (UrdPase), and the apparent Ki (appKi)
      values for these compounds were determined. Based on the inhibition data, a
      structure-activity relationship for the binding of nucleobase analogs to the
      enzyme was formulated, using uracil as a reference compound. Two compounds were
      identified as very potent inhibitors of T. gondii UrdPase, 5
      benzyloxybenzylbarbituric acid and 5-benzyloxybenzyluracil, which had appKi
      values of 0.32 and 2.5 microM, respectively. A comparison of the results from the
      present study, with similar studies on mammalian UrdPase and thymidine
      phosphorylase (dThdPase) (Niedzwicki et al., Biochem Pharmacol 32: 399-415, 1993)
      revealed that there are both similarities and differences between the catalytic
      site of T. gondii UrdPase and the catalytic sites of the mammalian enzymes with
      respect to binding of uracil analogs. One compound, 6-benzyl-2-thiouracil, was
      identified as a potent, specific inhibitor (appKi = 14 microM) of T. gondii
      UrdPase, relative to mammalian UrdPase and dThdPase.

PMID- 8250972
TI  - Effect of the antimalarial agents primaquine and (N'-3-acetyl-4-5-dihydro-2
      furanyl)-N4-(6-methoxy-8-quinolinyl)1,4-pent ane-diamine on oxidative stress and
      antioxidant defences in mice.
AB  - The effects of the newly developed antimalarial compound, CDRI 80/53 [(N'-3
      acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl)1,4- pentane-diamine],
      and primaquine (PQ) on the antioxidant system of mice were determined at equi
      effective antimalarial doses on enzyme systems responsible for protection against
      oxygen, i.e. hepatic superoxide dismutase and catalase. While PQ significantly
      inhibited these enzyme activities CDRI 80/53 did not. However, both compound
      80/53 and PQ increased the level of superoxide anion and lipid peroxidation. It
      is concluded that compound 80/53 has less effect on antioxidant defence enzymes
      than PQ.

PMID- 8250973
TI  - Suppression of lipopolysaccharide-induced fulminant hepatitis and tumor necrosis
      factor production by bisbenzylisoquinoline alkaloids in bacillus Calmette-Guerin
      treated mice.
AB  - The bisbenzylisoquinoline (BBI) alkaloids chondocurine, cycleanine, tetrandrine
      and berbamine were tested for their capacity to suppress hepatic injury and
      production of tumor necrosis factor (TNF) induced by lipopolysaccharide (LPS) in
      mice primed with bacillus Calmette-Guerin (BCG). When administered for three
      consecutive days before LPS injection, chondocurine, cycleanine and tetrandrine
      (10 mg/kg/day) strongly suppressed serum alanine aminotransferase (EC 2.6.1.1.)
      and aspartate aminotransferase (EC 2.6.1.2.); however, berbamine gave only slight
      protection. Chondocurine, cycleanine and tetrandrine but not berbamine
      significantly reduced the level of TNF which peaked 2 hr after LPS injection.
      This study shows that BBI alkaloids prevent BCG/LPS-induced hepatitis at least in
      part by suppressing TNF production.

PMID- 8250974
TI  - Absorption of N4-D-glucopyranosylsulphamethazine by rat everted intestinal sacs.
AB  - Absorption of the N4-D-glucose conjugate of sulphamethazine (glucose-SMZ, 0.5 mM)
      by isolated everted sacs of the rat small intestine was studied at 37 degrees and
      pH 6.6. Phlorizin (0.5-2.0 mM) significantly reduced (P < 0.05) both mucosal and
      serosal transfer of glucose-SMZ and inhibition of mucosal transfer appeared to be
      concentration-dependent. Phloretin (0.5 mM) and removal of Na+ from the
      incubation medium also diminished absorption of glucose-SMZ. Furthermore, D
      glucose (0.5 and 5.0 mM) inhibited mucosal and serosal transfer of the glycoside.
      The results suggest the D-glucose/Na+ cotransporter mediates absorption of
      glucose-SMZ from the small intestine of the rat. Thus, glucose-SMZ might be
      bioavailable from ingested tissues in which it is present.

PMID- 8250975
TI  - Participation of the CYP2D subfamily in lidocaine 3-hydroxylation and formation
      of a reactive metabolite covalently bound to liver microsomal protein in rats.
AB  - Lidocaine metabolism was investigated in rat liver microsomes and in a
      reconstituted system containing P450BTL, a cytochrome (P450) isozyme belonging to
      the CYP2D subfamily (Suzuki et al., Drug Metab Dispos 20: 367-373, 1992). P450BTL
      biotransformed lidocaine into 3-hydroxylidocaine (3-OH-LID) but not
      monoethylglycinexylidide and 2-methylhydroxylidocaine, in the reconstituted
      system including NADPH-P450 reductase and dilauroylphosphatidylcholine. An
      antibody against P450BTL inhibited microsomal lidocaine 3-hydroxylase activity by
      97%. Thus, P450BTL and/or its immunorelated P450 isozyme(s) belonging to the
      CYP2D subfamily appear to be involved in lidocaine 3-hydroxylation. Furthermore,
      the antibody also suppressed the amounts of a lidocaine metabolite(s) bound to
      microsomal protein. These results suggest that the CYP2D subfamily biotransformed
      lidocaine into 3-OH-LID via an epoxy intermediate, which binds to microsomal
      macromolecules.

PMID- 8250976
TI  - Species specificity of triphenylethylene derivatives and of compounds with a
      steroidal backbone for human and rat liver antioestrogen binding site (AEBS).
AB  - The binding affinity of derivatives of the triphenylethylene (TPE) antioestrogen
      tamoxifen and of steroidal compounds for human liver antioestrogen binding sites
      (AEBS) was compared with their binding affinity for rat liver AEBS. Despite the
      observation of some quantitative differences overall a highly significant
      correlation between the relative binding affinity (RBA) for human and rat liver
      AEBS was found for all compounds tested (r = 0.93, N = 19, P < 0.001). This was
      more pronounced for TPE derivatives (r = 0.83, N = 12, P < 0.01) than for
      cholesterol derived compounds (r = 0.64, N = 7, not significant). We conclude
      that AEBS from rat liver can be used instead of human livers as a model to study
      the interactions of antioestrogens with AEBS.

PMID- 8250977
TI  - Increase in catalase activity in developing rat brain cell reaggregation cultures
      in the presence of ethanol.
AB  - The aim of this investigation was to study the effects of ethanol on antioxidant
      enzymes in the developing brain, using reaggregation cultures of fetal rat brain
      cells as a model. The cultures were grown in the presence of 20 and 40 mM ethanol
      from day 2 until day 44 of the culture period, corresponding to a period in vivo
      from gestational day 17 to postnatal day 37. The catalase (EC 1.11.1.6) activity
      was consistently increased at all observation periods, from culture day 11 to day
      44, by both doses of ethanol, and an immunoblot showed that the amount of
      catalase protein was markedly increased. The activities of manganese and copper
      zinc superoxide dismutase (EC 1.15.1.1) and glutathione peroxidase (EC 1.11.1.9)
      were largely unaffected.

PMID- 8250978
TI  - [Complete primary structure of Bacillus thuringiensis extracellular
      ribonuclease].
AB  - Complete primary structure of an extracellular low molecular mass ribonuclease of
      Bacillus thuringiensis was determined using Edman degradation and mass
      spectrometry analysis of individual peptides obtained after hydrolysis of the
      protein by cyanogen bromide and staphylococcal protease. The peptides were
      isolated and purified by HPLC and denaturing PAGE. The enzyme consists of 109
      amino acid residues (Asp 8, Asn 6, Thr 6, Ser 10, Glu 3, Gln 1, Pro 3, Gly 9, Ala
      12, Val 7, Ile 7, Leu 7, Tyr 7, Phe 4, His 1, Arg 10, Trp 3 and Lys 5) and has a
      molecular weight of 12182 Da. A single difference was detected between primary
      structures of the enzyme and an extracellular ribonuclease of B. intermedius.

PMID- 8250979
TI  - [Neuroactive complexed zinc compounds from bovine brain].
AB  - The fraction obtained from acidic extract of bovine brain homogenate after
      several steps of chromatographic purification provokes spontaneous aggressive
      encounters in rats upon intracerebroventricular injection. The simultaneous long
      term raising of electric shock-induced aggression with the suppressing of
      muricidal and intraspecies aggressive behaviour has been observed. Intravenous
      and intraperitoneal injections of this fraction induce no behavioural changes in
      rats. It has been determined that the fraction consists of complex compounds of
      zinc with various aliphatic amines. A similar or higher behavioural activity has
      been discovered in series of synthetic complexes of zinc with different ligands,
      that are suggested for use in modelling any nervous and psychiatric disorders
      connected with an increased aggression level.

PMID- 8250980
TI  - [Interaction of photoactive oligothymidylate derivatives with HeLa cell
      chromatin].
AB  - Photoactive derivatives of d(pT)16, bearing arylazide, nitroarylazide and
      perfluoroarylazide residues, were used for the complementary addressed
      modification of DNA and proteins in chromatin. As compared with alkylating
      derivatives, the photoactive compounds possess higher efficiency and specificity,
      and shorter incubation times which prevents nucleus from degradation. These
      reagents can therefore be used for identification of proteins located near to
      particular DNA regions in chromatin.

PMID- 8250981
TI  - [Design of a universal biotin-containing oligonucleotide diagnostic kit for
      detecting viroid plant diseases].
AB  - A non-radioactive diagnosticum for plant viroid diseases has been designed, based
      on hybridization of a biotin-labeled 26-member oligonucleotide probe with the
      viroid RNA site identical for potato spindle tuber viroid and chrysanthemum stunt
      viroid. The biotin label has been introduced into the synthetic oligonucleotide
      probe by the high-yield acylation of the oligonucleotide aminoalkylamide with the
      biotin imidazolide or N-hydroxysuccinimide ester. Hybridization techniques have
      been elaborated for nucleic acids isolated from plant sap. The hybrids obtained
      have been detected with streptavidin and biotinylated alkaline phosphatase or
      with the covalent conjugate of streptavidin and alkaline phosphatase, the
      sensitivity being as low as 1 ng. The methodology used can be applied for
      revealing viroids and for large scale and quick investigation of plant cell
      cultures.

PMID- 8250982
TI  - [Intensification of genomic dactyloscopy by means of hybridization with modified
      oligonucleotides, forming duplexes with increased stability].
AB  - The modified oligodeoxyribonucleotide (m5C-n2A-m5C)5 containing 5-methylcytosine
      and 2-aminoadenine instead of cytosine and adenine residues, respectively has
      been used as a hybridisation probe in DNA fingerprinting. The oligonucleotide,
      due to the substitutions forms more stable duplexes with complementary sequence
      in DNA than the corresponding nonmodified pentadecanucleotide. The comparison
      with its natural counterpart displays considerably increased intensity of bands
      in patterns obtained with modified analog. The use of such analogues can increase
      sensitivity and shorten time of DNA fingerprinting.

PMID- 8250983
TI  - The national health insurance reform debate. Will the country get what it wants?

PMID- 8250984
TI  - Current methods and recent advances in the diagnosis of osteoporosis.

PMID- 8250985
TI  - Management of work disability. Resources for vocational rehabilitation.
AB  - OBJECTIVE: To review the state-federal vocational rehabilitation (SF-VR) system
      and its utilization by persons with rheumatic conditions. METHODS: SF-VR system
      instruction manuals, and literature on rheumatology rehabilitation, work
      disability, and rehabilitation counseling were reviewed. National and
      Massachusetts state SF-VR system data on persons with "arthritis and rheumatism"
      were analyzed. RESULTS: The SF-VR system is used by a small proportion of persons
      with rheumatic diseases. Fifty-two percent of clients with arthritis are employed
      after receiving services. CONCLUSION: Although evidence indicates that VR
      services for persons with rheumatic conditions improves their chances for
      reemployment, the SF-VR system is underutilized.

PMID- 8250986
TI  - Bone mineral density and knee osteoarthritis in elderly men and women. The
      Framingham Study.
AB  - OBJECTIVE: To examine the possible inverse relationship between osteoporosis and
      osteoarthritis (OA) by evaluating the association between bone mineral density
      (BMD) and knee OA in the Framingham Study cohort. METHODS: Of the 1,154
      Framingham Study cohort subjects in whom BMD measurements were obtained at
      biennial examination 20, 932 (81%) had had knee OA assessed during the Framingham
      Knee OA Study 4 years earlier. BMD of the proximal femur and radius was measured
      by densitometry. Knee OA was assessed from a weight-bearing anteroposterior
      radiography and graded on a scale of 0 (no OA) to 4 (severe OA). Osteophytes and
      joint space narrowing were also evaluated separately. Linear regression was used
      to test the association of BMD with knee OA, with osteophytes, and with joint
      space narrowing, after adjustment for age, body mass index, and mean number of
      cigarettes smoked per day. RESULTS: The subjects included 572 women and 360 men
      with an age range of 63-91 years (mean 71 years). Of these, 351 had no OA, 269
      had grade 1 OA, 170 had grade 2 OA, 93 had grade 3 OA, and 49 had grade 4 OA.
      Mean femoral BMD at the 3 proximal femur sites was 5-9% higher in men and women
      with either grade 1, grade 2, or grade 3 knee OA, compared with those with no
      knee OA (P < 0.0001). Mean femoral BMD in those with grade 4 OA was not higher
      than in those with no OA. Radius BMD was not associated with knee OA in subjects
      of either sex. Women with osteophytes had higher BMD compared with women with no
      osteophytes. Mean BMD did not differ across levels of joint space narrowing.
      CONCLUSION: We conclude that, among women, femoral BMD is higher in those with
      osteophytosis of the knee, and BMD is not necessarily associated with joint space
      narrowing.

PMID- 8250987
TI  - Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor
      necrosis factor alpha.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a chimeric monoclonal antibody
      to tumor necrosis factor alpha (TNF alpha) in the treatment of patients with
      rheumatoid arthritis (RA). METHODS: Twenty patients with active RA were treated
      with 20 mg/kg of anti-TNF alpha in an open phase I/II trial lasting 8 weeks.
      RESULTS: The treatment was well tolerated, with no serious adverse events.
      Significant improvements were seen in the Ritchie Articular Index, which fell
      from a median of 28 at study entry to a median of 6 by week 6 (P < 0.001), the
      swollen joint count, which fell from 18 to 5 (P < 0.001) over the same period,
      and in the other major clinical assessments. Serum C-reactive protein levels fell
      from a median of 39.5 mg/liter at study entry to 8 mg/liter at week 6 (P <
      0.001), and significant decreases were also seen in serum amyloid A and
      interleukin-6 levels. CONCLUSION: Treatment with anti-TNF alpha was safe and well
      tolerated and resulted in significant clinical and laboratory improvements. These
      preliminary results support the hypothesis that TNF alpha is an important
      regulator in RA, and suggest that it may be a useful new therapeutic target in
      this disease.

PMID- 8250988
TI  - Incidence of rheumatoid arthritis in central Massachusetts.
AB  - OBJECTIVE: To determine whether there is a secular decline in the incidence of
      rheumatoid arthritis (RA), as has been suggested by previous studies. METHODS: In
      the absence of comprehensive data in the United States population, we estimated
      RA incidence in a health maintenance organization population from 1987 through
      1990 and compared the rates with those in an earlier, similarly performed study
      from Rochester, Minnesota, which covered the years 1950 through 1974. RA
      estimates were based on our review of medical records of patients who had been
      diagnosed as having RA or related diseases during the period of January 1, 1987
      through December 31, 1990. RESULTS: Annual age-standardized incidence of classic
      or definite RA (according to the American College of Rheumatology [formerly, the
      American Rheumatism Association] 1958 criteria) in patients aged 18 or older was
      22 per 100,000 in men and 60 per 100,000 in women. The incidence of RA increased
      with age, with a marked increase in women older than 50. CONCLUSION: We found no
      secular change in RA incidence compared with the similarly ascertained historical
      data.

PMID- 8250989
TI  - The effect of long-term methotrexate therapy on hepatic fibrosis in rheumatoid
      arthritis.
AB  - OBJECTIVE: To evaluate the progression of hepatic fibrosis in patients with
      rheumatoid arthritis (RA) treated with methotrexate (MTX). METHODS: Fifteen
      patients receiving MTX for RA were prospectively studied by electron microscopic
      analysis of biopsy specimens. RESULTS: Five of the 15 patients had evidence of
      increased hepatic collagen after 2 years of MTX therapy. CONCLUSION: Hepatic
      fibrosis may progress in a subgroup of RA patients treated with MTX.

PMID- 8250990
TI  - Generalized osteoarthritis associated with increased insulin-like growth factor
      types I and II and transforming growth factor beta in cortical bone from the
      iliac crest. Possible mechanism of increased bone density and protection against
      osteoporosis.
AB  - OBJECTIVE: To investigate whether growth factors stored in bone might explain the
      increased bone density and resistance to osteoporosis in generalized
      osteoarthritis. METHODS: Levels of insulin-like growth factor (IGF) types I and
      II and transforming growth factor beta (TGF beta) were measured in extracts of
      cortical bone from the iliac crest obtained at necropsy from subjects with or
      without osteoarthritis of the hands. RESULTS: Concentrations of IGF-I, IGF-II,
      and TGF beta were significantly higher in extracts of bone powder from subjects
      in the osteoarthritis group than in extracts from subjects in the control group.
      CONCLUSION: The results suggest that the increased bone density and resistance to
      osteoporosis in patients with osteoarthritis may be associated with increased
      skeletal concentrations of IGF-I, IGF-II, and TGF beta and may reflect a
      generally increased biosynthetic activity of osteoblasts in these patients.

PMID- 8250991
TI  - Inhibition of cartilage proteoglycan release by a specific inactivator of
      cathepsin B and an inhibitor of matrix metalloproteinases. Evidence for two
      converging pathways of chondrocyte-mediated proteoglycan degradation.
AB  - OBJECTIVE: To investigate mechanisms of cartilage matrix destruction by a study
      of the effects of a specific inactivator of cathepsin B and an inhibitor of
      several matrix metalloproteinases (MMP) on cartilage proteoglycan release.
      METHODS: Cartilage explants were treated with either recombinant human
      interleukin-1 alpha (rHuIL-1 alpha) or retinoic acid in the presence or absence
      of the inhibitors, and proteoglycan release was quantitated. Tests for
      nonspecific effects of the inhibitors included reversibility, rates of protein
      synthesis and glycolysis, and effects on other rHuIL-1 alpha-mediated events.
      RESULTS: The cathepsin B inactivator inhibited rHuIL-1 alpha-stimulated
      proteoglycan release at nanomolar concentrations, but failed to significantly
      inhibit retinoic acid-stimulated proteoglycan release. An inhibitor of MMP was
      inhibitory to both rHuIL-1 alpha-stimulated release and retinoic acid-stimulated
      release. CONCLUSION: Cathepsin B is implicated in rHuIL-1 alpha-stimulated loss
      of cartilage proteoglycan. Its lack of involvement in retinoic acid-stimulated
      proteoglycan release suggests the existence of at least 2 pathways of cartilage
      proteoglycan breakdown, which may converge at the activation of a matrix
      prometalloproteinase.

PMID- 8250992
TI  - Loss of trabecular bone mineral density in systemic lupus erythematosus.
AB  - OBJECTIVE: To evaluate trabecular bone mineral density (BMD) in young ambulatory
      female patients with systemic lupus erythematosus (SLE). METHODS: Bone mineral
      density (gm/cm2) at the lumbar vertebrae (L1-L4) and at the left femur (neck,
      trochanter, intertrochanter, and Ward's triangle) was measured by dual x-ray
      absorptiometry in 46 SLE patients (mean age 31 years, mean disease duration 76
      months) and in 108 healthy female controls (mean age 32 years). Twenty-two of the
      SLE patients were receiving corticosteroids (CS) at the time of the study.
      RESULTS: Lumbar BMD in the SLE patients was less severely reduced than was BMD at
      the femoral sites, but the SLE group was closer to the lumbar fracture threshold
      of 0.812 gm/cm2 than was the control group (P = 0.0009). There were no
      significant differences between the SLE patients currently being treated with
      corticosteroids and those who were not (P > 0.3). BMD at Ward's triangle and at
      the femoral neck was not significantly reduced in the SLE patients. Total femoral
      BMD had a sensitivity of 76% and specificity of 62% in differentiating the SLE
      group from the controls. The positive predictive value was 61% and the negative
      predictive value was 89%. The prevalence of osteopenia in the SLE patients was
      25%. CONCLUSION: SLE causes significant trabecular bone loss, which is not due to
      corticosteroid therapy.

PMID- 8250993
TI  - Sjogren's syndrome presenting as hypokalemic periodic paralysis.
AB  - We describe a 21-year-old Hispanic woman who presented with hypokalemic paralysis
      as the initial manifestation of Sjogren's syndrome (SS). Our review of the
      English literature revealed 12 previously reported cases of SS and renal tubular
      acidosis (RTA). Paralysis often preceded the sicca complex in those patients.
      Renal function in the patients with hypokalemic paralysis was reduced compared
      with that in patients who had primary SS and RTA but no history of hypokalemic
      paralysis (P < 0.002). Hypokalemic periodic paralysis is a rare manifestation of
      SS. It is seen more often in patients with primary SS, may precede the classic
      sicca complex, and may serve as a clinical marker for more severe renal disease
      in patients who have primary SS and RTA.

PMID- 8250994
TI  - Systemic lupus erythematosus in a rhesus macaque.
AB  - We describe the clinical course and histopathologic findings in a rhesus macaque
      (Macaca mulatta) which developed a systemic inflammatory disorder resembling
      systemic lupus erythematosus (SLE). The manifestations of the SLE included
      antinuclear antibody, hemolytic anemia, membranoproliferative glomerulonephritis,
      and arthritis. To our knowledge, spontaneously occurring SLE has not previously
      been described in nonhuman primates.

PMID- 8250995
TI  - Idiopathic inflammatory myopathy of the antisynthetase (Jo-1) type associated
      with noncaseating granulomas.
AB  - The idiopathic inflammatory myopathies are a heterogeneous group of syndromes
      that share the finding of chronic muscle inflammation. Recently, serologic
      subtyping of autoantibodies found in patients with these syndromes has been used
      to identify distinct clinical entities. We describe a 36-year-old woman who,
      based on the findings of polymyositis documented by both electromyography and
      muscle biopsy, features of Raynaud's phenomenon, symmetric polyarthritis,
      "mechanic's hands," and Jo-1 antibody positivity, was considered to have the
      antisynthetase subset of idiopathic inflammatory myopathy. In addition, the
      patient had granulomatous synovitis, and noncaseating granulomas were found in a
      breast nodule. This is the first published report of granuloma formation in the
      antisynthetase syndrome.

PMID- 8250996
TI  - Resolution of severe lupus nephritis associated with Tripterygium wilfordii hook
      F ingestion.

PMID- 8250998
TI  - My mother, the patient.

PMID- 8250997
TI  - Odor identification ability among patients with Sjogren's syndrome.

PMID- 8250999
TI  - American Speech-Language-Hearing Association 1993 annual convention. Anaheim,
      California, November 19-22, 1993. Program and abstracts.

PMID- 8251000
TI  - Relationship between apolipoprotein E and low density lipoprotein particle size.
AB  - The relationships between the particle size of low density lipoproteins (LDL) and
      various lipid parameters, including apolipoprotein (apo) E concentration and apo
      E phenotype, were analyzed in plasma samples obtained from 196 apparently healthy
      35-year-old males. The LDL particle size was determined by gradient gel
      electrophoresis. Using stepwise multiple regression analysis it was found that
      LDL particle size correlated negatively to the plasma concentrations of
      triglyceride (r = -0.497, P < 0.001), apo E (r = -0.415, P < 0.001), apo B (r =
      0.395, P < 0.001) and cholesterol (r = -0.235, P < 0.001) and correlated
      positively to the plasma concentrations of apo A-I (r = 0.297, P < 0.001) and apo
      A-II (r = 0.145, P < 0.05). However, the LDL particle size did not differ
      significantly among the different apo E phenotypes. Indeed, when entered as a
      variable in the multiple regression analysis, the apo E phenotype was not
      correlated to the LDL particle size. It is concluded that the LDL particle size
      is related to the plasma concentrations of triglyceride, apo E, apo B, apo A-I,
      apo A-II and cholesterol and is not affected by the apo E phenotype in healthy 35
      year-old males.

PMID- 8251001
TI  - Smoking, haemostatic factors and lipid peroxides in a population case control
      study of peripheral arterial disease.
AB  - The aim of this study was to determine differences between cases of peripheral
      arterial disease and healthy controls in levels of haemostatic factors and lipid
      peroxides and the influence of cigarette smoking. The study groups were selected
      from the Edinburgh Artery Study which is a random sample survey of men and women
      aged 55-74 years. Mean levels of plasma fibrinogen, von Willebrand factor, beta
      thromboglobulin, plasminogen activator inhibitor (type I), cross-linked fibrin
      degradation products and lipid peroxides were markedly elevated in 121 study
      cases compared with 126 age- and sex-matched controls. For example, cross-linked
      fibrin degradation products had a geometric mean of 106.8 ng/ml (95% confidence
      interval (CI) 95.3, 119.8) in study cases and 74.7 ng/ml (95% CI 67.0, 83.4) in
      controls (P < 0.001). Inclusion of smoking in logistic regressions of each factor
      on peripheral arterial disease significantly reduced the odds of disease for von
      Willebrand factor and for cross-linked fibrin degradation products, but had
      little effect on the increased odds associated with fibrinogen, beta
      thromboglobulin, plasminogen activator inhibitor and lipid peroxides. We conclude
      that, in men and women in Edinburgh, peripheral atherosclerosis is associated
      with lipid peroxidation, endothelial disturbance, platelet activation, elevated
      fibrinogen, fibrin formation and increased inhibition of fibrinolysis. The most
      important effects of cigarette smoking in promoting atherosclerosis may be
      endothelial disturbance and fibrin formation.

PMID- 8251002
TI  - B-mode ultrasound images of the carotid artery wall: correlation of ultrasound
      with histological measurements.
AB  - B-mode ultrasound is being used to assess carotid atherosclerosis in
      epidemiological studies and clinical trials. Recently the interpretation of
      measurements made from ultrasound images has been questioned. This study examines
      the anatomical correlates of B-mode ultrasound of carotid arteries in vitro and
      in situ in cadavers. Twenty-seven segments of human carotid artery were collected
      at autopsy, pressure perfusion fixed in buffered 2.5% glutaraldehyde and 4%
      paraformaldehyde and imaged using an ATL UM-8 (10 MHz single crystal mechanical
      probe). Each artery was then frozen, sectioned and stained with van Gieson or
      elastin van Gieson. The thickness of the intima, media and adventitia were
      measured to an accuracy of 0.01 mm from histological sections using a calibrated
      eye graticule on a light microscope. Shrinkage artifact induced by histological
      preparation was determined to be 7.8%. Digitised ultrasound images of the artery
      wall were analysed off-line. The distance from the leading edge of the first
      interface (LE1) to the leading edge of the second interface (LE2) was measured
      using a dedicated programme. LE1-LE2 measurements were correlated against
      histological measurements corrected for shrinkage. Mean values for the far wall
      were: ultrasound LE1-LE2 (0.97 mm, S.D. 0.26), total wall thickness (1.05 mm,
      S.D. 0.37), adventitia (0.35 mm, S.D. 0.16), media (0.61 mm, S.D. 0.18), intima
      (0.09 mm, S.D. 0.13). Ultrasound measurements corresponded best with total wall
      thickness, rather than elastin or the intima-media complex. Excision of part of
      the intima plus media or removal of the adventitia resulted in a corresponding
      decrease in the LE1-LE2 distance of the B-mode image. Furthermore, increased wall
      thickness due to intimal atherosclerotic thickening correlated well with LE1-LE2
      distance of the B-mode images. B-mode images obtained from the carotid arteries
      in situ in four cadavers also corresponded best with total wall thickness
      measured from histological sections and not with the thickness of the intima plus
      media. In conclusion, the LE1-LE2 distance measured on B-mode images of the
      carotid artery best represents total wall thickness of intima plus media plus
      adventitia and not intima plus media alone.

PMID- 8251004
TI  - Inverse relationship between physical activity and plasma fibrinogen in
      postmenopausal women.
AB  - The relationship between habitual physical activity and plasma level of
      fibrinogen was investigated in a cohort of 180 postmenopausal women, aged 60-69
      years. Plasma fibrinogen was determined from prediluted plasma by adding an
      appropriate amount of thrombin to the sample. The time until fibrin formation
      occurred was measured. Physical activity during the month and year preceding the
      examination was assessed using self-administered questionnaires. There was a
      statistically significant inverse relationship between physical activity and
      fibrinogen (beta = -0.20; P = 0.005). For further analyses of the association
      between physical activity and fibrinogen the subjects were classified into three
      categories according to their weekly physical activity frequency: 0 to 1, 2 to 3,
      and 4 or more during the preceding month. The mean (S.D. [95% CI]) levels of
      fibrinogen from lowest to highest categories were: 3.49 (1.10 [2.99, 3.99]), 3.31
      (1.52 [2.82, 3.81]), and 3.20 (2.26 [2.73, 3.67]) g/l, respectively, when age,
      body mass index (BMI), smoking, alcohol intake, LDL-cholesterol and estrogen use
      were allowed for (P = 0.021). BMI was directly associated with fibrinogen (beta =
      0.30; P < 0.001), especially in the physically least active women. Smoking was
      directly (beta = 0.19; P = 0.006) and estrogen use inversely (beta = -0.15; P =
      0.037) related to plasma fibrinogen level. The present data suggest that in
      postmenopausal women a low level of physical activity is associated with a high
      level of plasma fibrinogen.

PMID- 8251003
TI  - Distribution of lipid variables in subjects in Belfast, Northern Ireland and
      Taiyuan, P R China.
AB  - To compare the plasma lipid, lipoprotein and apolipoprotein profiles of people of
      Chinese and European origin, a sample of 151 male Chinese subjects was selected
      from Taiyuan, Shanxi Province, P R China to 202 broadly age-matched subjects in
      Belfast who were selected as controls in a case-control study of myocardial
      infarction. Mean total cholesterol (TC) was 6.15 mmol/l in Belfast and 4.28
      mmol/l in Taiyuan. Low density lipoprotein cholesterol (LDL) was much higher in
      Belfast. High density lipoprotein cholesterol (LDL) was also higher in Belfast
      than in Taiyuan but the ratio of HDL to TC was lower in Belfast than Taiyuan.
      Triglyceride (TG) levels were similar and this was reflected in the relatively
      high level of apolipoprotein E (apo E) in the Chinese sample.

PMID- 8251005
TI  - Endothelialized myointimal thickening in the rat aorta as a result of extensive
      freeze injury.
AB  - The regeneration of rat aorta intima and medial layer was examined after
      extensive freeze injury that caused the death of both endothelial and smooth
      muscle cells. After 1 month complete re-endothelialization of the denuded area
      was observed. In parallel, myointimal thickening was formed by the smooth muscle
      cells (SMC) from the uninjured edges and its thickness increased with time. The
      SMC of myointimal thickening were stellate in the upper part and elongated near
      the internal elastic lamina. No regenerative response was seen in the medial
      layer, consisting only of elastic and collagen fibers, and its thickness was
      reduced during regeneration. These results show that the regenerative response of
      medial SMC to extensive freeze injury proceeds in the form of intimal thickening.

PMID- 8251006
TI  - Gender and employment grade differences in blood cholesterol, apolipoproteins and
      haemostatic factors in the Whitehall II study.
AB  - In the first Whitehall study, plasma cholesterol was a strong predictor of
      coronary heart disease (CHD) but it showed a positive association with grade of
      employment: the higher the grade the higher the level. Because it could not
      explain the higher rate of CHD in lower employment grades, further investigation
      of biochemical CHD risk factors has been conducted with data from the baseline
      examination of the Whitehall II cohort in 1985-88. These data also allow
      investigation of gender differences and the effect of menopause. Serum
      cholesterol (6860 men and 3374 women) and apolipoproteins A-I and B (apo AI and
      apo B) were measured in those aged 35-55 working in the London offices of twenty
      Civil Service departments. Plasma fibrinogen and factor VII were determined in 45
      55 year olds. The apo B/apo AI ratio (95% confidence interval) after age
      adjustment is lowest in premenopausal women: 0.557 (0.549-0.565), intermediate in
      postmenopausal women: 0.601 (0.589-0.613) and highest in men: 0.703 (0.698
      0.709). After age adjustment fibrinogen is higher in postmenopausal (2.90 (2.85
      2.95) g/l) than in premenopausal women (2.78 (2.71-2.84) g/l), who have higher
      levels than men (2.64 (2.62-2.67) g/l). A positive association with employment
      grade is seen for apo AI and a negative association is seen for fibrinogen, apo B
      (women only) and the apo B/apo AI ratio, after age adjustment. These patterns are
      consistent with the higher rates of CHD in lower grades. Cholesterol and factor
      VII show no gradient with our sensitive measure of social position. After
      adjusting for the effects of smoking rates, alcohol consumption, exercise and
      dietary pattern, as well as age, ethnicity, body mass index and report of
      symptoms, the regression coefficient for apo AI on employment grade is reduced by
      43% in men and 70% in women. Corresponding reductions for fibrinogen are 53% and
      65%. These attenuations suggest that a considerable part of the social gradients
      in apo AI and fibrinogen are explained by variations in health related
      behaviours. The remaining gradients may represent effects independent of these
      behaviours.

PMID- 8251007
TI  - Oxidation of low density lipoprotein by bovine and porcine aortic endothelial
      cells and porcine endocardial cells in culture.
AB  - Oxidation of low density lipoprotein (LDL) in atherosclerotic lesions may be
      involved in converting macrophages into cholesterol-laden foam cells, a major
      characteristic of atherosclerotic lesions. It has been reported, and is widely
      believed, that endothelial cells derived from rabbit, pig and human aortas, but
      not those derived from bovine aortas, are capable of oxidising LDL in vitro. We
      have re-investigated this subject and found that during a 48-h incubation period
      bovine aortic endothelial cells (both in primary culture and in subcultures) were
      capable of consistently modifying LDL, increasing its uptake and degradation by
      macrophages by more than 4-fold. Incubation of LDL with bovine aortic endothelial
      cells for only 24 h, however, produced inconsistent modification of the LDL,
      whereas mouse peritoneal macrophages consistently modified LDL in 24 h. The
      modification of LDL by bovine aortic endothelial cells was an oxidative process,
      as the chain-breaking antioxidants, alpha-tocopherol and probucol, completely or
      greatly inhibited it. Thus, bovine aortic endothelial cells are capable of
      oxidising LDL but they are slower at doing so than are certain other types of
      cells. Nitric oxide generated by activated macrophages has very recently been
      shown to inhibit their oxidation of LDL. We have therefore investigated whether
      or not the inhibition of the constitutive nitric oxide synthase of bovine or
      porcine aortic endothelial cells would increase their rate of oxidation of
      LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251008
TI  - Etofibrate increases binding of low and high density lipoprotein to human
      platelets of patients with type II hyperlipoproteinemia.
AB  - Previous work suggested an influence of etofibrate, a diester of nicotinic acid
      and clofibric acid, on lipoprotein receptors. Besides its beneficial effects on
      plasma lipoprotein levels of decrease in total cholesterol, LDL-cholesterol and
      triglycerides and increase in HDL-cholesterol, etofibrate was shown to inhibit
      platelet function. In order to further evaluate platelet-lipoprotein
      interactions, the effects of etofibrate on plasma lipids and lipoproteins on the
      specific binding of normal [111In]LDL and [111In]HDL onto platelets as well as
      its effect on platelet function were evaluated in 8 patients affected by Type II
      hyperlipoproteinemia (HLP). In all patients binding was saturable and indicated
      high affinity binding sites capable of binding 927 +/- 233 ng protein of
      [111In]LDL/10(9) platelets (Kd 12 +/- 3 micrograms protein/ml) and 1496 +/- 435
      ng protein of [111In]HDL/10(9) platelets (Kd 14 +/- 3 micrograms protein/ml). The
      capacity of native LDL (HDL) to displace bound [111In]LDL ([111In]HDL) by half
      (IC50) amounted to 22 +/- 9 micrograms protein/ml (26 +/- 8 micrograms
      protein/ml). Following a 6-week treatment period with etofibrate (500 mg twice
      daily), decrease in plasma total cholesterol, LDL-cholesterol and apolipoprotein
      (apo) B and increase in HDL-cholesterol and apo AI was correlated to a
      significant (P < 0.01) increase in LDL- as well as HDL-receptor binding. The
      platelet binding capacity increased to 1085 +/- 212 ng protein/10(9) platelets
      (Kd 8 +/- 3 micrograms protein/ml) for [111In]LDL and to 1867 +/- 266 ng
      protein/10(9) platelets for [111In]HDL (Kd 11 +/- 3 micrograms protein/ml).
      Platelet function studies demonstrated significantly (P < 0.01) reduced platelet
      aggregation in response to ADP and thromboxane formation after 6 weeks of
      etofibrate therapy. These findings in patients with HPL Type II indicate in vivo
      upregulation of specific [111In]LDL as well as [111In]HDL binding sites on human
      platelets associated with reduced platelet activation following etofibrate
      therapy.

PMID- 8251009
TI  - Endothelin-converting enzyme activity in serum lipoprotein and total cholesterol
      level.

PMID- 8251010
TI  - Reduction of plasma lipoprotein(a) by allylestrenol.

PMID- 8251011
TI  - Cytosolic Ca2+ gradients, Ca2+ binding proteins and synaptic plasticity.
AB  - Trains of spikes encoded by presynaptic neurons are decoded into rises in
      cytosolic Ca2+ concentration both in presynaptic terminals and in postsynaptic
      dendrites. Intracellular [Ca2+] rises trigger neurotransmitter release and also
      induce short- and long-term modifications of synaptic efficacy. These
      modifications can be potentiation or depression depending on the intensity of
      stimuli. A dynamic mechanism, "dynamic decoding", is proposed to understand the
      multiplicity of the functions of Ca2+, based on recent knowledge of Ca2+ binding
      proteins and of the dynamics of Ca2+ signaling. The dynamic model is in many ways
      superior to static models, and may be applied to various neuronal functions
      including the induction of long-term plasticity in cerebral cortex.

PMID- 8251012
TI  - Cardiorespiratory response to exercise after the Fontan operation: a serial
      study.
AB  - OBJECTIVES: The purpose of this study was to assess whether there is
      deterioration of aerobic capacity over time after the Fontan operation in
      individual patients. BACKGROUND: We previously observed that maximal aerobic
      capacity after the Fontan operation was lower in older patients than in younger
      patients. It was unclear whether this represented a decrease in aerobic capacity
      with time after operation or was a function of studying patients of different
      ages at different times postoperatively. METHODS: All patients who had more than
      one postoperative exercise study were included. There were 25 patients (19 male,
      6 female), aged 3.8 to 39 years at the time of the operation. The first exercise
      test was performed, on average, 2.2 years after the Fontan operation, and the
      last exercise test was performed, on average, 5.9 years (range 1.8 to 13) after
      the operation. In 11 patients, coronary sinus drainage was left on the pulmonary
      venous side. Five patients had had a previous Glenn operation. Exercise was
      performed to exhaustion with use of a 3-min incremental cycle protocol. RESULTS:
      Exercise duration, oxygen uptake, blood pressure, respiratory rate, minute
      ventilation, pulmonary blood flow index, exercise factor, ST-T wave changes and
      the prevalence of arrhythmias were similar during the first and last tests.
      Exercise systemic arterial blood oxygen saturation decreased from the first to
      the last postoperative test (p < 0.006) regardless of age. The percent of
      predicted heart rate, at rest and during maximal exercise, decreased more in
      older patients from the first to the last test (p < 0.05 for rest and exercise).
      CONCLUSIONS: In this select group of patients, exercise tolerance remained
      relatively unchanged over the range of 13 years after the Fontan operation. Heart
      rate at rest and during maximal exercise decreased more than predicted for age in
      older patients. A small but significant progressive decrease in systemic arterial
      blood oxygen saturation was found. The former might represent abnormal sinus node
      function in patients with functional single ventricle, and the latter might
      represent a tendency toward development of abnormal ventilation/perfusion
      patterns resulting from the development of small pulmonary arteriovenous fistulas
      or an effect of position of the coronary sinus postoperatively.

PMID- 8251013
TI  - Cerebral cortical pathology of sporadic olivopontocerebellar atrophy.
AB  - We examined the cerebral cortices of six brains from patients with sporadic
      olivopontocerebellar atrophy (s-OPCA), five control brains including four from
      patients who had died without neurological disease, and one from a patient with
      Holmes-type cerebellar cortical atrophy. Distinct laminar astrocytosis of the
      motor cortices in the fifth layer were demonstrated in 4 of 6 s-OPCA cases and in
      none of the control cases by immunohistochemistry for glial fibrillary acidic
      protein. The astrocytosis localized in the primary motor cortex and its
      distribution pattern were clearly different from those of so-called glial
      cytoplasmic inclusion. This cortical astrocytosis appears to be characteristic of
      s-OPCA and may reflect the pathology of the primary motor cortex.

PMID- 8251014
TI  - A 2 base pair deletion in the RDS gene associated with butterfly-shaped pigment
      dystrophy of the fovea.

PMID- 8251015
TI  - Bipolar disorder: are repeated episodes associated with neuroanatomic and
      cognitive changes?

PMID- 8251016
TI  - Cellular mechanisms governing synaptic development in Drosophila melanogaster.
AB  - The neuromuscular connections of Drosophila are ideally suited for studying
      synaptic function and development. Hypotheses about cell recognition can be
      tested in a simple array of pre- and postsynaptic elements. Drosophila muscle
      fibers are multiply innervated by individually identifiable motoneurons. The
      neurons express several synaptic cotransmitters, including glutamate, proctolin,
      and octopamine, and are specialized by their synaptic morphology,
      neurotransmitters, and connectivity. During larval development the initial
      motoneuron endings grow extensively over the surface of the muscle fibers, and
      differentiate synaptic boutons of characteristic morphology. While considerable
      growth occurs postembryonically, the initial wiring of motoneurons to muscle
      fibers is accomplished during mid-to-late embryogenesis (stages 15-17). Efferent
      growth cones sample multiple muscle fibers with rapidly moving filopodia. Upon
      reaching their target muscle fibers, the growth cones rapidly differentiate into
      synaptic contacts whose morphology prefigures that of the larval junction.
      Mismatch experiments show that growth cones recognize specific muscle fibers, and
      can do so when the surrounding musculature is radically altered. However, when
      denied their normal targets, motoneurons can establish functional synapses on
      alternate muscle fibers. Blocking synaptic activity with either injected toxins
      or ion channel mutants does not derange synaptogenesis, but may influence the
      number of motor ending processes. The molecular mechanisms governing cellular
      recognition during synaptogenesis remain to be identified. However, several cell
      surface glycoproteins known to mediate cellular adhesion events in vitro are
      expressed by the developing synapses. Furthermore, enhancer detector lines have
      identified genes with expression restricted to small subsets of muscle fibers
      and/or motoneurons during the period of synaptogenesis. These observations
      suggest that in Drosophila a mechanism of target chemoaffinity may be involved in
      the genesis of stereotypic synaptic wiring.

PMID- 8251017
TI  - [The effectiveness of a program of smoking prevention among Mexican
      schoolchildren].
AB  - The main objective of this study was to determine if a program emphasizing
      training for coping with the social pressures to smoke cigarettes is effective in
      preventing initial experimentation in the same population. Six elementary schools
      in Tijuana, Mexico, were included in this prospective study with the
      participation of 168 sixth-graders. After a baseline survey students were
      randomly assigned to an intervention and a control group. A program that
      emphasizes peer-pressure resistance skills to avoid smoking was applied to the
      intervention group. The control group received no intervention. After 10 months a
      second survey was carried out in both groups. A significantly smaller proportion
      of subjects in the intervention group experimented with tobacco during the follow
      up period when compared with controls (8.1% vs 20%; p < 0.05). Although designed
      as a prevention tool, the program also had a therapeutic effect. The proportion
      of subjects in the intervention group that quit smoking was significantly higher
      than that of the control group (72% vs 34.78%; p < 0.01). We conclude that this
      peer pressure resistance skill program was effective in preventing
      experimentation with tobacco among sixth graders in Tijuana, Mexico.

PMID- 8251018
TI  - Infection in inguinal hernia repair considering biomaterials and antibiotics.
AB  - Synthetic biomaterials have been incriminated for promoting wound infection.
      Perioperative antibiotics have received praise for reducing the rate of infection
      after certain operations. These claims were tested in a cooperative multicenter
      prospective study of 2,493 inguinal hernia repairs. This study was done to
      examine the effect of prophylactic antibiotics in primary and recurrent inguinal
      hernia repaired with synthetic biomaterials. Clinical signs and symptoms of wound
      infection and the results of each infected repair are reported. The rate of
      infection was about 1 percent, whether or not biomaterials or antibiotics were
      used. More than 70 percent of wound infections occurred in patients 60 years of
      age or older. Removal of biomaterials from the infected wounds was not necessary
      and generally is not recommended. Recurrence has not occurred in any of the
      infected repairs. With or without prosthetic repair, the treatment of infected
      inguinal hernia wounds was relatively simple, of reasonable cost and concluded
      with a good result. The expense incurred for routine prophylactic antibiotic
      treatment in inguinal hernia operation could not be reconciled by any benefits
      obtained.

PMID- 8251019
TI  - Prevention of intraoperative hypothermia by preoperative skin-surface warming.
AB  - BACKGROUND: Intraoperative hypothermia initially results from internal
      redistribution of heat facilitated by anesthesia-induced vasodilation.
      Preinduction skin-surface warming minimizes postinduction hypothermia in
      anesthetized volunteers. However, its efficacy might be reduced in surgical
      situations, because of multiple sources of heat loss. METHODS: Intraoperative
      core and mean skin temperatures were measured during total hip arthroplasty in 16
      patients, randomly assigned to be covered preoperatively with a warming blanket
      for > or = 90 min (prewarmed group) or not covered (unwarmed group). RESULTS:
      During the first hour of anesthesia, core temperature decreased more than twice
      as much in the unwarmed group (-0.7 +/- 0.1 degree C; mean +/- SE) than in the
      prewarmed patients (-0.3 +/- 0.1 degree C). At the end of surgery, core
      temperature was 36.3 +/- 0.1 degree C in the prewarmed group and 35.2 +/- 0.2
      degree C in the unwarmed group. During recovery, seven patients obviously
      shivered in the unwarmed group and none in the prewarmed group. CONCLUSIONS:
      Preanesthetic skin-surface warming reduces the initial postinduction hypothermia
      in surgical patients, preventing intraoperative hypothermia and postoperative
      shivering even for procedures lasting 3 h or longer.

PMID- 8251020
TI  - Managing postoperative pain.

PMID- 8251021
TI  - Metabolic effects of omega-3 fatty acids in type 2 (non-insulin-dependent)
      diabetic patients.
AB  - The metabolic effects of a 3-week dietary supplement of a fish oil concentrate
      was examined in mildly obese, normotriglyceridemic men with non-insulin-dependent
      diabetes mellitus (NIDDM) treated with hypoglycemic agents (n = 20). Patients
      were randomized into two groups, receiving 15 ml per day of fish oil (Martens
      Oil, Norway) containing 3.1 g of omega-3 fatty acids (FA) (n = 10) or placebo (n
      = 10). Whereas fish oil led to the expected increase in the ratio of omega-3 to
      omega-6 FA in serum phospholipids, reflecting the increase in omega-3 FA intake,
      it did not alter fasting or mixed meal stimulated blood glucose, plasma insulin,
      and C-peptide concentrations. No changes in insulin action were noted, estimated
      by the metabolic clearance rates of glucose at plasma insulin levels of
      approximately 100 microU/ml and 1,400 microU/ml during a hyperinsulinemic,
      isoglycemic clamp; no changes were seen in insulin binding to erythrocytes. We
      conclude that during short-term administration, no adverse effects of low dose
      fish oil on glucose homeostasis were found in mildly obese NIDDM patients treated
      with oral hypoglycemic agents.

PMID- 8251022
TI  - An open door policy in ICU.

PMID- 8251023
TI  - Markers of osteoarthritis and cartilage research in animal models.
AB  - Research in the past year on evaluating serum and synovial fluid markers in
      osteoarthritis has helped to define more precisely how the components of
      cartilage extracellular matrix correlate with disease progression. Novel,
      cartilage-specific markers, such as the cartilage oligomeric matrix protein, have
      been detected in serum and synovial fluid, and their relevance in the
      pathogenesis of osteoarthritis must now be determined. Precisely defined
      cartilage matrix protein changes in surgically induced and spontaneously
      occurring animal models of osteoarthritis have contributed to a better
      understanding of the dynamics of cartilage and bone reparative and degradative
      pathways.

PMID- 8251024
TI  - Lithium lengthens the period of circadian rhythms in lesioned hamsters bearing
      SCN grafts.
AB  - Lithium lengthens the free-running period of circadian rhythms in a wide variety
      of organisms. The object of the present study was to examine the effects of
      lithium treatment on free-running activity rhythms in suprachiasmatic nuclei
      lesioned (SCN-X) hamsters that had recovered circadian rhythmicity following
      transplantation of fetal anterior hypothalamic grafts containing the
      suprachiasmatic nuclei (SCN). The animals were housed individually in cages
      equipped with running wheels, and locomotor activity was monitored using a
      computer-based data acquisition system. At the end of the behavioral tests,
      animals were anesthetized and perfused. Brain sections were immunostained for
      vasoactive intestinal peptide (VIP) and vasopressin-associated neurophysin (NP)
      to evaluate the extent of the lesion and the presence of a functional graft. In
      both intact and in SCN-X grafted animals, lithium lengthened the period of free
      running activity without affecting the amount of activity or the precision of the
      rhythm.

PMID- 8251025
TI  - Prevention of melanoma in Torbay.

PMID- 8251026
TI  - Role of a telencephalic nucleus in the delayed song learning of socially isolated
      zebra finches.
AB  - Male zebra finches normally learn their song from adult models during a
      restricted period of juvenile development. If song models are not available then,
      juveniles develop an isolate song which can be modified in adulthood. In this
      report we investigate the features of juvenile experience that underly the timing
      of song learning. Juvenile males raised in soundproof chambers or in visual
      isolation from conspecifics developed stable isolate song. However, whereas
      visual isolate song notes were similar to those of colony-reared males,
      soundproof chamber isolates included many phonologically abnormal notes in their
      songs. Despite having stable isolate songs, both groups copied new notes from
      tutors presented to them in adulthood (2.7 notes per bird for soundproof chamber
      isolates, 4.4 notes per bird for visual isolates). Old notes were often modified
      or eliminated. We infer that social interactions with live tutors are normally
      important for closing the sensitive period for song learning. Lesions of a
      forebrain nucleus (IMAN) had previously been shown to disrupt juvenile song
      learning, but not maintenance of adult song for up to 5 weeks after surgery. In
      this study, colony-reared adult males given bilateral lesions of IMAN retained
      all their song notes for up to 4-7.5 months after lesioning. However, similar
      lesions blocked all song note acquisition in adulthood by both visual and
      soundproof chamber isolates. Other work has shown that intact hearing is
      necessary for the maintenance of adult zebra finch song. We infer that auditory
      pathways used for song maintenance and acquisition differ: IMAN is necessary for
      auditorily guided song acquisition--whether by juveniles or adults--but not for
      adult auditorily guided song maintenance.

PMID- 8251027
TI  - [A comparative study of rifapentine treatment and three years follow-up on
      initial pulmonary tuberculous].
AB  - A clinical study about the efficacy of rifapentine in the treatment and 3 years'
      follow up on initial pulmonary tuberculous patient. Altogether 267 patients of
      initial pulmonary tuberculosis with positive smears were randomly divided into 3
      groups; Group I with DL473 twice-weekly (2HE+L2/7H2L2), Group IIARFp twice-weekly
      (2HE+R2/7H2R2) and Group IIBRFP daily (2HRE/7HR) for controls. Results are: the
      conversion rate to smear negative are 96.0%, 96.4% and 97.1% respectively (P >
      0.05); the sputum conversion rate by cultures are 98.0%, 95.7% and 96.4%
      respectively (P > 0.05). From X-Ray pictures, the treatment effect of Group I are
      similar to that of Group IIB. But in Group I with less side action were observed.
      The relapse rate of the three groups are 2.6%, 3.8% and 3.1% respectively (P >
      0.05). From this investigation, we can draw a conclusion that the twice-weekly of
      rifapentine has at least an effect similar to rifampicin given daily. Further
      investigation of DL473 once weekly will soon be followed.

PMID- 8251028
TI  - Effects of ranitidine alone and in combination with chlorpheniramine on histamine
      induced wheal and flare and psychomotor performance.
AB  - Some reports suggest that addition of an H2 antagonist increases the efficacy of
      H1 antagonist but the influence on the side effect profile of antihistamines are
      largely unknown. The effects of ranitidine, chlorpheniramine, their combination
      and placebo on histamine induced wheal and flare, psychomotor performance and
      subjective symptoms were studied in 6 healthy male volunteers in a double blind
      randomized and cross-over (Latin square) study. Ranitidine significantly reduced
      the histamine induced wheal at 4 hrs (P < 0.05). Chlorpheniramine and the
      combination significantly reduced both histamine induced wheal and flare at 2 hrs
      and at 4 hrs (P < 0.05). Addition of ranitidine reduced the feeling of sleepiness
      produced by chlorpheniramine, though other subjective symptoms were not affected.
      None of the treatment schedules produced any consistent change in the psychomotor
      performance of the volunteers.

PMID- 8251029
TI  - Treatment of the post-mastectomy pain syndrome with topical capsaicin.
AB  - Twenty-one patients with post-mastectomy pain syndrome (PMPS) were entered in an
      open-label trial of topical 0.025% capsaicin treatment (3 daily applications for
      2 months). Out of 19 evaluable patients, 2 (10.5%) reported complete
      disappearance of all symptoms, and 11 (57.9%) had a reduction of pain which was
      never worse than mild at the end of treatment. Three months after cessation of
      treatment, 11 of 13 of the responding patients continued to have good pain
      relief, with only 1 continuing to use capsaicin. Treatment was well tolerated
      with no drop-out due to side effects. This is the first independent confirmation
      of the usefulness of capsaicin in the PMPS, following the recent publication of a
      randomized, placebo-controlled clinical study showing significant pain relief
      with 0.075% capsaicin but not with vehicle cream. Further experimental and
      clinical research on the properties of capsaicin in other painful peripheral
      neuropathies is desirable.

PMID- 8251030
TI  - [Antiemetic efficacy of granisetron in the treatment of pediatric cancer--(1).
      Clinical evaluation of granisetron at a dose of 40 micrograms/kg].
AB  - Seventeen children with various types of cancer were studied on the effectiveness
      of antiemetic drug, granisetron, by a crossover randomized trial; receiving
      granisetron (40 micrograms/kg; n = 53) or conventional antiemetics, during
      intensive chemotherapy. In the patients given granisetron nausea and vomiting
      were well controlled (83.0%), compared with 33.3% of conventional (non
      granisetron) group. The mean number of vomiting episodes for each 6h-period over
      24h after chemotherapy was reduced markedly in the patients given granisetron,
      compared with conventional therapy. One patient developed paraesthesia of the
      hand after injection of granisetron as the adverse effect, which recovered to
      normal spontaneously after 3 hrs. Our data indicated that antiemetic effect of
      granisetron was superior to conventional antiemetic drugs, both in terms of
      clinical effectiveness and usefulness.

PMID- 8251031
TI  - ECGF and heparin determine differentiation of cloned cerebral endothelial cells
      in vitro.
AB  - Protein expression patterns of morphologically different cloned capillary
      endothelial cells from porcine and murine brain cortices were examined. Type I
      cells, grown in medium containing heparin and endothelial cell growth factor
      (ECGF), exhibited a polygonal, cobblestone appearance and appeared to replicate
      the cells of the blood-brain barrier endothelium. Type II cells, grown in medium
      without heparin and ECGF, were elongated and appeared to replicate capillaries in
      central nervous system tissue. Cells of both phenotypes stained positive by the
      specific endothelial cell marker Bandeiraea simplicifolia lectin. The expression
      of alpha smooth-muscle actin (mRNA and protein) was taken as a marker for type II
      cells. By use of 2-D gel images and the GELLAB II system, a data base was created
      revealing that two proteins (90 kDa, pI 5.1, and 35 kDa, pI 5.7) were exclusively
      expressed in type I cells. Furthermore, the synergistic action of ECGF and
      heparin in respect to the phenotypic determination of cerebral endothelial cells
      was demonstrated.

PMID- 8251032
TI  - Motor abnormalities and changes in the noradrenaline content and the
      cytoarchitecture of developing cerebellum following X-irradiation at birth.
AB  - We have studied the developmental time-course of changes in the noradrenaline
      (NA) content of cerebellum (CE), cytoarchitecture of the cerebellar cortex, and
      motor abnormalities induced by the exposure of the cephalic end of rats to a
      single dose (5 Gy) of X-irradiation immediately after birth. At all ages
      examined, i.e., from postnatal (PN) d 5 to 90, CE from exposed animals show a
      marked atrophy, with an agranular cortex that has lost its layered structure.
      Purkinje cells are scattered at all depths in the cortex, and their primary
      dendrite is randomly oriented. The motor syndrome includes dystonia-like
      movements, a fine tremor, and an ataxic gait. Being progressive, the abnormal
      movements are evident from PN d 10, and fully developed by d 30. On the other
      hand, no differences in cerebellar NA content between X-irradiated rats and age
      matched nonirradiated controls were detected from PN d 5 to 60. However, at PN d
      90 a significant increase in NA content of CE from exposed animals is found when
      compared to either age-matched controls (+36%, p < 0.01), or data from irradiated
      rats obtained at PN d 5 to 60 (p < 0.01). These results indicate a temporal
      dissociation between the motor and cytoarchitectural abnormalities and the
      increase in cerebellar NA content produced by a single dose of X-rays at birth.
      The late increase in cerebellar NA content might represent a compensatory
      response of noradrenergic terminals to an altered information flow out of the
      cerebellar cortex induced by the ionizing noxa.

PMID- 8251033
TI  - Expression of viral T-antigen in pathological tissues from transgenic mice
      carrying JC-SV40 chimeric DNAs.
AB  - Immunostaining methods were used to detect viral T-antigen and the cellular
      protein p53 in pathological tissues obtained from transgenic mice carrying JC
      SV40 hybrid viral DNAs. A transgenic mouse carrying the SV40 regulatory region
      and JC virus (JCV) T-antigen-coding sequences exhibited an SV40-characteristic
      choroid plexus papilloma that expressed JCV T-antigen and p53. JCV-associated
      pathology was observed in two other mice in which the JCV regulatory signals
      directed SV40 T-antigen-induced adrenal neuroblastomas and brain neoplastic
      cells. However, these mice also exhibited an SV40-characteristic osteosarcoma and
      abdominal lymphoma that contained SV40 T-antigen and p53-positive cells.
      Contrasting thymic pathology was observed in the two types of mice where the SV40
      regulatory region directed a JCV T-antigen-induced thymoma in one mouse, and the
      JCV regulatory region directed SV40 T-antigen-induced thymic hypoplasia in two
      other mice.

PMID- 8251034
TI  - Reduction in striatal D2 dopamine receptor mRNA and binding following AF64A
      lesions.
AB  - Unilateral lesions by a cholinotoxin, receptor autoradiography, and in situ
      hybridization techniques were employed to determine if dopaminergic receptors are
      located on cholinergic interneurons in the caudate-putamen (CPu). Lesion of the
      CPu with small amounts of the cholinotoxin AF64A resulted in a significant
      decrease in D2 receptor mRNA and D2 receptor binding. The loss was more
      pronounced in lateral and central portions of the CPu. Results obtained using
      [3H] SCH23390 binding to D1 receptors indicated that there was no change in this
      dopamine receptor subtype in the AF64A-lesioned CPu. A decrease in D2 receptor
      mRNA and receptor binding in AF64A-lesioned animals indicates that a population
      of postsynaptic D2 receptors is associated with the cholinergic interneurons.
      Lack of any change in [3H]SCH23390 binding in the AF64A-lesioned animals suggests
      that D1 receptors are not located on cholinergic neurons. These results provide
      evidence to support the selectivity of the lesion when used as indicated.

PMID- 8251035
TI  - 3 alpha-Hydroxysteroid-5 beta-oxidoreductase in tissue cultures of Digitalis
      lanata.
AB  - Putative intermediates of cardenolide biosynthesis, namely progesterone,
      pregnenolone, 5 beta-pregnane-3,20-dione or 5 beta-pregnan-3 beta-ol-20-one, were
      administered to light- or dark-grown shoot cultures of Digitalis lanata. The
      unsaturated compounds were reduced to their respective 5 alpha-pregnanes, 5 beta
      pregnane-3,20-dione was reduced to 5 beta-pregnan-3 alpha-ol-20-one and 5 beta
      pregnan-3 beta-ol-20-one was isomerized to the respective 3 alpha-pregnane.
      Suspension cultures of Digitalis lanata, on the other hand, accumulated both the
      3 alpha- and the 3 beta-isomer of 5 beta-pregnan-3-ol-20-one when incubated in
      the presence of 5 beta-pregnane-3,20-dione. When 5 beta-pregnan-3 alpha-ol-20-one
      was administered the cultured cells accumulated large amounts of the 3 beta
      isomer together with small amounts of 5 beta-pregnane-3,20-dione, which may be
      regarded as an intermediate during the isomerization reaction. Cell-free,
      buffered extracts from light-grown shoots were shown to reduce 5 beta-pregnane
      3,20-dione almost exclusively to 5 beta-pregnan-3 alpha-ol-20-one when 0.05 M
      MgCl2 were present in the incubation mixture. Under these conditions the
      formation of 5 beta-pregnan-3 beta-ol-20-one was inhibited. The enzyme activity
      could be recovered from membrane-free supernatants. Optimum enzyme activity
      occurred at pH 7.0 and 42 degrees C. The energy of activation was 56.2 kJ/mol and
      the enzyme reaction was found to be NADPH-dependent. SH reagents were essential
      for enzyme activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251036
TI  - Translocation of adenine nucleotides in the mitochondria of male sterile and male
      fertile sorghum.
AB  - The translocation of ATP from the inside to the outside of the mitochondrial
      membrane has been studied in a male sterile (2219 A) and a male fertile (2219 B)
      line of sorghum. The translocation of ATP was found to be substantially lower in
      case of mitochondria from the male sterile line. The affinity of adenine
      nucleotides to the translocator proteins of the mitochondrial membrane was found
      to be almost one half in case of 2219 A as compared to 2219 B when the Km for ATP
      ADP was determined by two different assays. It is proposed that the inadequate
      supply of ATP in the cytosol resulting from its inefficient translocation may
      contribute to the male sterility in this line.

PMID- 8251037
TI  - Complete sequence of one copy of the psbA gene from the thermophilic
      cyanobacterium Synechococcus elongatus.
AB  - One copy of the psbA gene which codes for the photosystem II reaction center D-1
      protein from the thermophilic cyanobacterium Synechococcus elongatus has been
      sequenced. It is feasible that a disulfide bridge between D-1 Cys212 and D-2
      Cys212 is responsible for the thermostability of the photosystem II reaction
      center from Synechococcus elongatus.

PMID- 8251038
TI  - Linear free energy relationships for N(7)-substituted guanosines as substrates of
      calf spleen purine nucleoside phosphorylase. Possible role of N(7)-protonation as
      an intermediary in phosphorolysis.
AB  - Quantitative structure-activity relationships (QSAR) for a series of N(7)
      substituted guanosines as substrates for calf spleen purine nucleoside
      phosphorylase (PNP) were developed, and compared with those for acid hydrolysis
      of these analogues. There is no correlation between the rates for enzymatic
      phosphorolysis and acid hydrolysis, indicating that for the enzymatic reaction
      labilization of the glycosidic bond is not the only, nor the predominant, effect
      of N(7)-substitution. Multiple regression analysis of the enzymatic process
      revealed that optimal substrate properties (minimal Michaelis constant) are
      associated with the Taft electronic constant equal zero and a substituent size,
      parametrized by the Taft steric constant, smaller than that for a methyl group.
      These results support the hypothesis of protonation of the N(7)-position of the
      base by the enzyme as a catalytic mechanism for calf spleen PNP. Attention is
      drawn to the postulated similar mechanism of action of other purine N
      glycosidases, including plant antiviral proteins which function as RNA N
      glycosidases, and possibly some DNA N-glycosidases which function as repair
      enzymes.

PMID- 8251039
TI  - Inhibition of dihydrofolate reductase by mofebutazon.
AB  - Mofebutazon, in contrast to phenylbutazon, inhibits dihydrofolate reductase in a
      concentration-dependent manner. An apparent Ki for mofebutazon and dihydrofolate
      reductase in the presence of NADPH as electron donor and dihydrofolate as
      electron acceptor of approximately 0.2 mM was calculated.

PMID- 8251040
TI  - Structural and conformational studies on bio-active flavonoids. Crystal and
      molecular structure of a complex formed between 2',6'-dimethoxyflavone and
      orthophosphoric acid: a model for flavone-nucleotide interactions.
AB  - In order to investigate mechanisms of action of flavones at the molecular level,
      we have prepared a complex between a flavone and orthophosphoric acid which can
      be considered as a simplest model of interaction between a flavone and a more
      complex biological phosphate such as nucleotide, coenzyme or DNA. With
      orthophosphoric acid, the title flavone forms crystals which have 1:2
      stoichiometry (C17H14O4.2H3PO4). This compound was found to be the 1:1 salt co
      crystallized with the unionized molecular acid C17H15O4+.H2PO4-.H3PO4. The
      symmetry is monoclinic, space group P2(1)/n and unit cell dimensions a =
      15.571(2), b = 7.369(1), c = 17.837(2) A, beta = 100.84(1) degrees. One molecule
      of phosphoric acid is present as a solvate molecule of crystallization, but the
      other is ionized and protonates the carbonyl oxygen, introducing conformational
      and bond distance changes in the flavone. The dihedral angle between the
      benzopyrone and phenyl rings is 47 degrees. Complexes with phosphate groups
      involve strong hydrogen bonds and are expected to play important roles in
      biomolecular structures.

PMID- 8251041
TI  - Makaluvamines, marine natural products, are active anti-cancer agents and DNA
      topo II inhibitors.
AB  - The makaluvamines were isolated from a sponge of the genus Zyzzya by following
      bioactivity against the human colon carcinoma cell line, HCT 116. These compounds
      have considerable cytotoxic activity. The makaluvamines appear to be acting
      through inhibition of DNA topoisomerase II. The compounds show enhanced toxicity
      toward a topoisomerase II-cleavable complex-sensitive cell line, they inhibit
      topoisomerase II decatenation of kinetoplast DNA in vitro. Makaluvamine C was
      shown to produce protein-linked DNA double-strand breaks, and makaluvamine A
      produced DNA double-strand breaks by neutral filter elution in a dose-dependent
      fashion similar to 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA). The
      makaluvamines also increased the life span of nude mice bearing solid tumors of
      human ovarian cancer cells.

PMID- 8251042
TI  - Benzo-gamma-pyrone analogues of geiparvarin: synthesis and biological evaluation
      against B16 melanoma cells.
AB  - Chromone, flavone and xanthone analogues of geiparvarin (1) are described.
      Compounds 2a and 2b are more active in inhibiting the proliferation of F10
      metastatic murine melanoma cells. In particular, 2a is 13 times more active at
      microM concentration after 48 h exposure.

PMID- 8251043
TI  - The linking chain length in bridged aldehyde-substituted pyridinium dimers
      modulates a slow reversible binding that affects supercoiling of plasmid DNA.
AB  - Bridged aldehyde substituted pyridinium dimers bind to DNA. Binding induces
      retardation of the electrophoretic migration of circular plasmid due to
      relaxation of supercoiling. Binding to DNA is slow and reversible and depends on
      the length of linking chain, pH, ionic strength and temperature. It is postulated
      that release of topological stress results from the disruption of hydrogen
      bonding between complementary bases, a hypothesis consistent with facilitated
      attack of DNA by formaldehyde promoted by the bridged compounds.

PMID- 8251044
TI  - DNA sequence-selective binding of head-to-tail linked bis-lexitropsins: relation
      of phasing to cytotoxic potency.
AB  - A series of polymethylene, -(CH2)n-tether-linked head-to-tail bislexitropsins (n
      = 1-7) have been synthesized in order to assess the effect on DNA binding of
      phasing, that arises because of lack of dimensional correspondence between
      oligopeptides and oligonucleotides. Binding constants to poly(dA-dT), estimated
      from ethidium displacement, are from 0.55 to 16.66 x 10(8) M-1. Comparable Ka
      values for calf thymus DNA and for poly(dG-dC) are approximately 10(6) and
      approximately 10(5) M-1, respectively reflecting the anticipated AT preference.
      Sequence-selective binding was examined by reflecting the anticipated AT
      preference. Sequence-selective binding was examined by methylethidium propyl
      ethylenediamine tetraacetic acid (MPE) complementary strand footprinting on an
      EcoRI/HindIII restriction fragment of pBR322 DNA with r = 0.08 and 0.32. Ligands
      bearing N-methylpyrrole dipeptide moieties linked by -(CH2)n, where n = 2, 4 or
      6, give evidence of bidentate binding in (AT)n-rich sequences from footprinting
      at r = 0.32. By contrast, those ligands linked by (CH2)n, where n = 1, 3, 5 or 7,
      bind in a predominantly monodentate fashion. Cystostatic activity against KB
      human nasopharyngeal cancer cells has shown enhanced potency, compared with
      distamycin, for those linked bis-lexitropsins with n = 2, 4 and 6. That the
      increased potency may be attributed to more effective DNA binding in the latter
      cases is indicated by the fact that the n = 1, 3, 5 and 7 ligand homologues do
      not exhibit comparable enhanced cytotoxic potency.

PMID- 8251045
TI  - African American issues in geriatric psychiatry: a perspective on research
      opportunities.
AB  - Racial, ethnic, and cultural factors influencing mental health in later life are
      important to study in their own right. However, they also offer an opportunity to
      expand our understanding of mental health and mental illness in older adults
      independent of race, ethnicity, or culture. Any time an opportunity arises to
      examine a problem from a different perspective, chances increase that new light
      will be shed on the problem. For example, while suicide is greatest in older
      Americans compared with any other US population group, it is less frequent in
      older blacks than older whites. Why? Among the different theories that have been
      advanced, one holds that older African Americans in reaching later life have
      surmounted more threats to self-esteem (compared with whites) and are thereby
      better adapted to new challenges associated with aging. Still, the discrepancy in
      suicide rates between older blacks and whites remains an important research
      question. In studying suicide with attention to racial and ethnic variables, the
      opportunity presents itself to gain a more fundamental understanding of suicide
      itself--to the benefit of all older adults, indeed to the benefit of all age
      groups. This paper focuses on some African American issues pertinent to geriatric
      psychiatry and identifies areas for further research. In addition to a selected
      literature review, the author draws on his own research from a 20-year
      longitudinal study, initiated in 1971, of a senior citizens' apartment building
      in Washington, DC, with a predominantly African American population.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8251046
TI  - Age and cerebral infarction: a postmortem study of 77 cases of cerebral infarcts
      in the middle cerebral artery territory.
AB  - Adverse effect of age on ischemic stroke short-term mortality was reported in
      some studies and attributed either to more frequent extracerebral causes of death
      or to an increased severity of ischemia in the aged brain. Relationship between
      age, size of infarcts, and causes of death were studied in 77 consecutive
      patients who died from infarction in the middle cerebral artery territory. Area
      of infarcts was assessed by planimetry, and results were expressed as an index of
      infarcted area. No significant relationship was found between age and the size of
      infarcts, the cause of death, or the interval from stroke to death. These results
      do not support the hypothesis of an increased severity of ischemia in the aged
      brain.

PMID- 8251047
TI  - Sodium valproate in the treatment of behavioral disturbance in dementia.
AB  - Management of the behavioral complications of dementia, including agitation and
      aggression, presents a tremendous challenge to families and caregivers of
      afflicted patients. Most previous pharmacotherapies have shown minimal efficacy
      and significant side effects. We report our initial, open-label experience using
      the anticonvulsant sodium valproate in four dementia patients with severe
      behavioral disturbance. The drug was well tolerated by all patients, with no side
      effects or laboratory abnormalities, during 1- to 3-month trials. Two patients
      showed significant improvement in behavior, and a third had a transient response.
      Valproate may be a useful agent in the treatment of behavioral disturbance in
      dementia; controlled trials are needed to document its efficacy.

PMID- 8251048
TI  - Assessment of cognitive impairment: relationship of the Dementia Rating Scale to
      the Mini-Mental State Examination.
AB  - The relationship between the Dementia Rating Scale (DRS) and the Mini-Mental
      State Examination (MMSE) was examined in 50 patients referred for
      neuropsychological assessment. The correlation between these two tests was
      moderately high (rho = .72; Pearson r = .78), supporting previous findings.
      Linear regression analysis yielded equations that allow prediction of scores from
      one test to the other. Neither age nor education correlated significantly with
      these two tests. Examination of the five DRS subscales and the eleven MMSE items
      revealed some unexpected relationships. These results suggest that these two
      cognitive screening instruments evaluate some overlapping mental abilities;
      however, the validity of the individual items and subscales is not well
      supported.

PMID- 8251049
TI  - Prevalence of advance directives and guardianship in nursing home patients.
AB  - The Patient Self-Determination Act (PSDA) now requires federally funded nursing
      homes to inform newly admitted patients of their right to determine their future
      medical care. Many nursing home patients may not be able to understand these
      rights, given the high prevalence of mental disorders, particularly dementia, in
      this population, and well need family members for assistance. Prior to the onset
      of the PSDA we surveyed the families of all residents of a large, proprietary
      nursing home to determine whether family members understood the concept of
      advance directives and guardianship. We also ascertained the rate of use of these
      instruments in the population studied. We found that the majority of family
      member respondents understood these concepts, but that substantial proportions of
      both competent and incompetent patients lacked surrogate decision-making
      authority, either in the form of a court-appointed guardian or a written advance
      directive instrument. Informing newly admitted patients and their families about
      advance directives is warranted because many lack these plans. However, the high
      proportion of incompetent patients among nursing home patients indicates the need
      to encourage currently competent patients to formulate advance directives prior
      to nursing home placement.

PMID- 8251050
TI  - Convex third ventricle: a possible sign for dementia using MRI.
AB  - The shape and thickness of the third ventricles were studied with magnetic
      resonance imaging in 46 patients under evaluation for memory impairment. We
      compared this population with 23 subjects imaged for other reasons. The study
      group consisted of patients with diagnoses of probable dementia of the
      Alzheimer's type (DAT; 35.6%), multi-infarct dementia (MID; 22.2%), depression
      (8.9%), alcoholic dementia (6.7%), other dementias (OD; 13.2%) and no dementia
      (6.7%). Within the study group, there were no significant differences across
      diagnostic categories for duration of symptoms or level of education. Patients
      with DAT were, however, more impaired than others (Mini-Mental State Examination
      scores: DAT 14.6 [+/- 8.2] versus MID 17.4 [+/- 6.2] versus OD 21.2 [+/- 6.4]).
      Demented subjects were more likely than nondemented individuals to have a convex
      third ventricle and greater wall separation. The results suggest that the shape
      of the third ventricle may correlate with dementia. Possibly, the dorsal medial
      nucleus of the thalamus is involved in the dementia.

PMID- 8251051
TI  - Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
AB  - Thiamine is important not only in the metabolism of acetylcholine but also in its
      release from the presynaptic neuron. Pathologic, clinical, and biochemical data
      suggest that thiamine deficiency is detrimental to the cholinergic system and
      that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two
      previous studies reported contradictory results in patients with dementia of
      Alzheimer's type treated with 3 g/day of thiamine. In the present study, we
      examined the effects of 3 to 8 g/day thiamine administered orally. Our results
      suggest that thiamine at these pharmacologic dosages may have a mild beneficial
      effect in dementia of Alzheimer's type. The mechanism of the observed effect is
      unknown, but the findings warrant further investigation, not only for their
      therapeutic implications but for their possible etiologic clues. In addition, the
      results suggest long-term carry-over effects that should be considered in the
      design of future studies.

PMID- 8251052
TI  - Alzheimer's disease: the problem of incorrect clinical diagnosis.
AB  - We reviewed the medical records of eight patients clinically diagnosed with
      Alzheimer's disease who were found on autopsy to have neuropathologic findings
      inconsistent with Alzheimer's disease. The clinical criteria for the diagnosis of
      probable Alzheimer's disease from the National Institute of Neurological and
      Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders
      Association (NINCDS/ADRDA) were retrospectively applied to these patients. The
      patients presented with clinical features atypical for Alzheimer's disease early
      in the course of the disease, including focal neurologic findings, gait
      abnormalities, motor speech abnormalities, and extrapyramidal features. Attention
      to these clinical red flags may decrease the likelihood of misdiagnosis of
      Alzheimer's disease in a patient with a non-Alzheimer's disease cause of
      dementia.

PMID- 8251053
TI  - Selected psychiatric symptoms associated with rate of cognitive decline in
      patients with Alzheimer's disease.
AB  - We examined the relation between selected psychiatric symptoms and the average
      rate of decline in different areas of cognition in patients with Alzheimer's
      disease. Measures of decline were computed by determining patients' average rates
      of decline on the underlying factors of the Mini-Mental State Examination (MMSE).
      Patients with agitation or wandering declined more rapidly on the total MMSE
      score than did patients without either symptom. The Following Commands factor
      accounted for almost all of this decline. The findings suggest a relation between
      the presence of certain behavioral problems in Alzheimer's disease and decline in
      particular cognitive areas.

PMID- 8251054
TI  - Aluminum induces neurite elongation and sprouting in cultured hippocampal
      neurons.
AB  - It has been reported that the aluminum content in the human brain increases with
      age, and it is particularly high in those with Alzheimer's disease. In this
      study, we found that a low aluminum concentration (100 mumol/L) in the culture
      media of opossum hippocampal neurons can induce extensive neurite outgrowth (ie,
      elongation and branching of neurites) and sprouting (ie, outgrowth of filiform
      processes from neurite varicosities) within 48 hours. Such changes in neurite
      morphology were remarkably similar to those described in the aged or Alzheimer's
      disease brain. Neurites that responded to aluminum varied greatly in length,
      thickness, and branching pattern. Many neurites appeared to have no clear
      directional growth pattern because they frequently changed their course and
      formed a meshwork of neurites with others originating from the same cell body.
      Sprouting neurites varied in length, thickness, and branching pattern, but they
      always originated from a globular enlargement of neurites along the neurite shaft
      or at the terminal end. Such growth pattern and extensive sprouting of neurites
      did not fit the growth pattern displayed by the control neurons. Our findings
      suggest that aluminum may be involved in the neuronal remodeling characteristic
      of aging and Alzheimer's disease.

PMID- 8251056
TI  - WHO in a new Europe.

PMID- 8251055
TI  - Failure of CT scan to detect ischemic lesions in patients with dementia.
AB  - Although clinical series have described relatively high accuracy in the ability
      of computed tomographic (CT) scan to detect significant cerebrovascular damage in
      patients with dementia, a recent neuropathologically controlled study failed to
      document that relationship. We now present clinical, neuroradiologic (CT), and
      neuropathologic information on four patients in whom CT scans did not contribute
      to the diagnosis of multi-infarct dementia or mixed dementia, despite clinical
      and neuropathologic evidence of infarcts. In one patient, the failure of CT scan
      to detect ischemic lesions may be attributable to less sensitive neuroradiologic
      criteria in use at the time of the examination. In the other three, even
      neuroradiologic review after the pathology was known failed to reveal the
      infarcts. These observations suggest the advisability of caution in using CT scan
      as a criterion for the presence or absence of cerebrovascular damage in patients
      with dementia.

PMID- 8251057
TI  - The amino acid sequence of a protein from wheat kernel closely related to
      proteins involved in the mechanisms of plant defence.
AB  - The amino acid sequence of wheatwin1, a monomeric protein of 125 residues
      isolated from wheat kernel (variety S. Pastore), is reported. Wheatwin1 is highly
      homologous (95%) to barwin, a protein from barley seed, which was shown to be
      related to the C-terminal domain of two proteins encoded by the wound-induced
      genes win1 and win2 in potato and to a protein encoded by the same domain of the
      hevein gene (hev1) in rubber tree. Similarly to barwin, wheatwin1 contains six
      cysteine residues all linked in disulfide bridges and the N-terminal residue is
      pyroglutamate. Moreover, structural studies performed on wheatwin1 and win1
      protein by predictive methods demonstrated that these proteins and barwin are
      closely related in the secondary structure also. The high level of homology found
      with the product of win1, win2, and hev1 genes strongly suggests that barwin and
      wheatwin1 play a common role in the mechanism of plant defence.

PMID- 8251058
TI  - Conformation of the abortifacient protein pinellin: a circular dichroic study.
AB  - The conformation of pinellin was studied by circular dichroism, which showed a
      minimum at 223 nm and a double maximum at 198-200 nm. The protein was rich in
      beta-sheet (about 40%) with little alpha-helix, based on current CD analyses. It
      was stable between pH4 and 10 beyond which it unfolded reversibly, but in
      alkaline solution, prolongly stored at, say, pH 12, it became irreversibly
      denatured. Thermal denaturation indicated a transition between 55 degrees and 68
      degrees C; the solution at 80 degrees C was partially renatured upon air-cooling
      back to room temperature. Addition of sodium dodecyl sulfate caused a sharp
      increase in alpha-helix, which leveled off at 0.25 mM surfactant.

PMID- 8251059
TI  - Cyclic modulation of cross-linking interactions of microtubule-associated protein
      2 with actin and microtubules by protein kinase FA.
AB  - The ATP.Mg-dependent type-1 protein phosphatase activating factor (factor FA) was
      identified as a brain protein kinase that could phosphorylate microtubule
      associated protein-2 (MAP-2) and thereby inhibit cross-linking interactions of
      MAP-2 with actin filaments and microtubules isolated from porcine brain. The
      phosphorylation sites were found to be equally located on both projection and
      microtubule-binding domains of MAP-2. Phosphoamino acid analysis revealed that
      the phosphorylation sites were on both serine and threonine residues, indicating
      that factor FA is a serine/threonine-specific MAP-2 kinase. Conversely, factor FA
      was further identified as a MAP-2 phosphatase activator that could promote the
      dephosphorylation of 32P-MAP-2 phosphorylated by factor FA itself and thereby
      potentiate cross-linking interactions of MAP-2 with actin and microtubules.
      Furthermore, the two opposing functions of factor FA can be selectively modulated
      in a reciprocal manner by pH change. For instance, alkaline pH could stimulate
      factor FA to work as a MAP-2 kinase but simultaneously block it to work as a MAP
      2 phosphatase activator to potentiate the inhibition on the cross-linking
      interactions of MAP-2 with actin and microtubules. Taken together, the results
      provide initial evidence that a cyclic modulation of cross-linking interactions
      of MAP-2 with actin filaments and microtubules can be controlled by factor FA,
      representing an efficient cyclic cascade control mechanism for rapid structural
      and functional regulation of neuronal cytoskeletal system.

PMID- 8251060
TI  - Amino acid substitutions outside a preselected antigenic region in hemoglobin
      affect the binding to monoclonal antibodies obtained by immunization with the
      synthetic region.
AB  - It is often assumed that amino acid substitutions outside a protein antigenic
      site have no effect on the reactivity of a protein variant with antibodies,
      especially monoclonal antibodies (mAbs). Substitutions that exert an effect on
      the reactivity of a protein variant with mAbs are frequently considered to be
      within the antigenic site of the mAb. To test this assumption, two mAbs [IgG1(k)
      and IgG2a(k)] were prepared by immunization with a synthetic peptide
      corresponding to region 63-78 of the alpha chain of human hemoglobin (Hb). The
      peptide was used as an immunogen in its free form (i.e., without conjugation to a
      carrier), so that the results will not be made ambiguous by peptide modification
      nor by an immune response to sites spanning peptide and protein carrier. In
      addition to their reaction with human Hb, the mAbs were also studied with four
      primate Hbs which had no substitutions within region alpha 63-78 and only a
      limited number of substitutions which occurred outside of, and at considerable
      distances in three-dimensional (3D) structure from, this region. Inhibition
      studies revealed substantial differences in the binding affinities of some of the
      primate Hbs, relative to human Hb. Some of the substitutions caused major
      decreases in binding, although they were at considerable distances in the 3D
      structure from the indicated site residues. It is concluded that substitutions in
      a protein, even when distant from an antigenic site, can exert major influences
      on the protein's reactivity with anti-site mAbs.

PMID- 8251061
TI  - Limited proteolysis of Saccharomyces cerevisiae phosphoenolpyruvate
      carboxykinase.
AB  - Incubation of Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase with
      trypsin under native conditions cases a time-dependent loss of activity and the
      production of protein fragments. Cleavage sites determined by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis and sequence analyses identified
      protease-sensitive peptide bonds between amino acid residues at positions 9-10
      and 76-77. Additional fragmentation sites were also detected in a region
      approximately 70-80 amino acids before the carboxyl end of the protein. These
      results suggest that the enzyme is formed by a central compact domain comprising
      more than two thirds of the whole protein structure. From proteolysis experiments
      carried out in the presence of substrates, it could be inferred that CO2 binding
      specifically protects position 76-77 from trypsin action. Intrinsic fluorescence
      measurements demonstrated that CO2 binding induces a protein conformational
      change, and a dissociation constant for the enzyme CO2 complex of 8.2 +/- 0.6 mM
      was determined.

PMID- 8251062
TI  - Amino acid sequences of ovomucoid third domains from 27 additional species of
      birds.
AB  - Ovomucoids consist of a single polypeptide chain which is composed of three
      tandem Kazal domains. Each Kazal domain is an actual or putative protein
      inhibitor of serine proteinases. Ovomucoid third domains were already isolated
      and sequenced from 126 species of birds (Laskowski et al., 1987, 1990). This
      paper adds 27 new species. A number of generalizations are made on the basis of
      sequences from 153 species. The residues that are in contact with the enzyme in
      enzyme-inhibitor complexes are strikingly hypervariable. While the primary
      specificity residue, P1, is the most variable; substitutions occur predominantly
      among aliphatic, hydrophobic residues. Consensus sequences for an avian ovomucoid
      third domain, for a b-type Kazal domain (i.e., a COOH terminal domain of
      multidomain inhibitors) and for a general Kazal domain are given. Finally, the
      individual new sequences are briefly discussed.

PMID- 8251063
TI  - Limited tryptic digestion of recombinant human interleukin-2: structure-binding
      relationships with the alpha chain of the interleukin-2 receptor.
AB  - The surface topography and structural features of interleukin-2 (IL-2) in
      relation to its interaction with the alpha subunit of its receptor (IL-2R alpha)
      have been probed by limited tryptic digestion followed by detailed structural
      analyses. Four sensitive cleavage sites in IL-2 (Lys8, Lys9, Lys35, and Arg38)
      were identified as surface amino acids, suggesting that they are potential
      binding sites for IL-2R alpha. To examine the involvement of these residues in IL
      2R alpha binding, a truncated IL-2 molecule lacking the amino-terminal residues
      through Arg38 was generated and it was found to be incapable of binding IL-2R
      alpha in a solid-phase receptor binding sequencing assay. These studies have led
      to the conclusion that the IL-2R alpha contact region of IL-2 includes residues
      Lys35 and Arg38. This finding is supported by the refined three-dimensional
      structure of IL-2 in which these residues are located outside of the compact
      bundle of four helices and thus are readily available for interaction with IL-2R
      alpha.

PMID- 8251064
TI  - Probing the fatty acid binding site of beta-lactoglobulins.
AB  - The interactions of fatty acids with porcine and bovine beta-lactoglobulins were
      measured using tryptophan fluorescence enhancement. In the case of bovine beta
      lactoglobulin, the apparent binding constants for most of the saturated and
      unsaturated fatty acids were in the range of 10(-7) M at neutral pH. Bovine beta
      lactoglobulin displays only one high affinity binding site for palmitate with an
      apparent dissociation constant of 1 x 10(-7) M. The strength of the binding was
      decreasing in the following way: palmitate > stearate > myristate > arachidonate
      > laurate. Caprylic and capric acids are not bound at all. The affinity of beta
      lactoglobulin for palmitate decreased as the pH of the incubation medium was
      lowered and BLG/palmitate complex was not observed at pH's lower than 4.5.
      Surprisingly, chemically modified bovine beta-lactoglobulin and porcine beta
      lactoglobulin did not bind fatty acids in the applied conditions.

PMID- 8251065
TI  - Modification of maize phosphoenolpyruvate carboxylase by Woodward's reagent K.
AB  - Maize leaf phosphoenolpyruvate carboxylase was completely and irreversibly
      inactivated by treatment with micromolar concentrations of Woodward's reagent K
      (WRK) for about 1 min. The inactivation followed pseudo-first-order reaction
      kinetics. The order of reaction with respect to WRK showed that the reagent
      causes formation of reversible enzyme inhibitor complex before resulting in
      irreversible inactivation. The loss of activity was correlated to the
      modification of a single carboxyl group per subunit, even though the reagent
      reacted with 2 carboxyl groups per protomer. Substrate PEP and PEP+Mg2+ offered
      substantial protection against inactivation by WRK. The modified enzyme showed a
      characteristic absorbance at 346 nm due to carboxyl group modification. The
      modified enzyme exhibited altered surface charge as seen from the elution profile
      on FPLC Mono Q anion exchange column. The modified enzyme was desensitized to
      positive and negative effectors like glucose-6-phosphate and malate. Pretreatment
      of PEP carboxylase with diethylpyrocarbonate prevented WRK incorporation into the
      enzyme, suggesting that both histidine and carboxyl groups may be closely
      physically related. The carboxyl groups might be involved in metal binding during
      catalysis by the enzyme.

PMID- 8251066
TI  - The disulfide bridges of the immunoglobulin-like domains of Fc gamma RIIIB are
      essential for efficient expression and biological activity.
AB  - The immunoglobulin G receptor Fc gamma RIIIB belongs to the immunoglobulin
      superfamily as two extracellular domains show homology to the immunoglobulin
      domains. Since some residues in these domains, such as the two cysteines, are
      supposed to form an intrachain disulfide bridge are so commonly conserved, they
      may be of importance for correct folding. Site-directed mutagenesis and
      expression in BHK21 confirmed this supposition for the Fc gamma RIIIB. Replacing
      both cysteines in the first and/or second domain by serines reduced the surface
      expression level by 50%, whereas the ligand binding capability was 20-30% of that
      seen in cells expressing the wild-type receptor. Replacing one of the four
      cysteines resulted in the loss of surface expression. Exchanging the conserved
      tryptophan in the first domain by phenylalanine only slightly affected the ligand
      binding (25%), whereas the surface expression remained unchanged.

PMID- 8251067
TI  - Separation and characterization of the A chain and B chain in beta 1-bungarotoxin
      from Bungarus multicinctus (Taiwan banded krait) venom.
AB  - The interchain disulfide bond between A chain and B chain of beta 1-bungarotoxin
      (beta 1-Bgt) was selectively cleaved by dithiothreitol, and the A and B chains
      were separated by HPLC. The separated A and B chains did not show detectable
      enzymatic activity and lethal toxicity, but exhibited an immunoreactivity with
      anti-beta 1-Bgt antibody. Analytical isoelectrofocusing revealed that the A chain
      is a neutral subunit with pI = 7.4, and the B chain is a basic one with pI = 9.6.
      The A chain exhibited a Ca(2+)-binding ability as revealed by fluorescence
      measurement. Moreover, fluorescence studies showed that the intact interchain
      disulfide bond is essential for maintaining the hydrophobic character of
      substrate binding site in beta 1-Bgt and stabilizing the architectural
      environment of Trp-19 in the A chain. However, combination of the A chain and B
      chain failed to restore the biological activities and physiochemical properties
      which the intact beta 1-Bgt possessed. These, together with our previous result
      that the Trp-19 of the A chain is involved in substrate binding, suggest that the
      integrity of the interchain disulfide bond favors the maintenance of the active
      conformation of beta 1-Bgt.

PMID- 8251068
TI  - Conformational changes of alpha-lactalbumin and its fragment, Phe31-Ile59,
      induced by sodium dodecyl sulfate.
AB  - Conformational changes of bovine alpha-lactalbumin in sodium dodecyl sulfate
      (SDS) solution were studied with the circular dichroism (CD) method using a
      dilute phosphate buffer of pH 7.0 and ionic strength 0.014. The proportions of
      alpha-helix and beta-structure in alpha-lactalbumin were 34% and 12%,
      respectively, in the absence of SDS. In the SDS solution, the helicity increased
      to 44%, while the beta-structure disappeared. In order to verify the structural
      change from beta-structure to alpha-helix, the moiety, assuming the beta
      structure in the alpha-lactalbumin, was isolated by a chymotryptic digestion. The
      structure of this alpha-lactalbumin fragment, Phe31-Ile59, was almost disordered.
      However, the fragment adopted a considerable amount of alpha-helical structure in
      the SDS solution. On the other hand, the tertiary structure of alpha-lactalbumin,
      detected by changes of CD in the near-ultraviolet region, began to be disrupted
      before the secondary structural change in the surfactant solution. Dodecyl
      sulfate ions of 80 mol were cooperatively bound to alpha-lactalbumin. Although
      the removal of the bound dodecyl sulfate ions was tried by the dialysis against
      the phosphate buffer for 5 days, 4 mol dodecyl sulfates remained per mole of the
      protein. The remaining amount agreed with the number of stoichiometric binding
      site, determined by the Scatchard plot, indicating that the stoichiometric
      binding was so tight.

PMID- 8251069
TI  - Comparison of secondary structures of insulin and proinsulin by FTIR.
AB  - Although the structure of insulin is known in great detail, that of proinsulin
      has been little investigated, except for a few CD and NMR studies. The secondary
      structures of human proinsulin are now compared with those of insulin by Fourier
      Transformed Infrared (FTIR) studies. The deconvolved and second derivative
      spectra of proinsulin and insulin in the amide I' band region are closely similar
      with peaks corresponding to alpha-helix, irregular helix, and 3(10) helix at
      nearly identical positions. For both proteins, the relative contents of the above
      structures as calculated from the peak areas are in good agreement with the
      values obtained from the known structure of crystalline porcine insulin. However,
      compared with insulin, proinsulin has markedly more unordered structures as
      indicated by the area under the peak at 1643.4 cm-1. In addition, both peak
      positions and relative areas for turn structure of the prohormone are different
      from those for insulin. It appears from the above that the A-and B-chain segments
      of proinsulin and insulin are similar in their secondary structures, especially
      in helices. The C-chain segment is largely unordered except in a few beta-turns.

PMID- 8251070
TI  - Recombinant human IL-6 expressed in E. coli undergoes selective N-terminal
      degradation: evidence that the protein consists of a stable core and a
      nonessential flexible N-terminal.
AB  - A synthetic gene for human interleukin-6 has been expressed in E. coli. The
      protein has been purified and renatured and has the same activity as natural
      human IL-6 using the 7TD1 cell proliferation assay. The protein undergoes
      specific cleavage by a thiol protease, yielding two new N-termini at Arg-9 and
      His-15. The truncated proteins retain full biological activity. The degradation
      results in the loss of sharp amide resonances in the 1H-NMR spectrum, and little
      change to the ultraviolet CD spectrum. Several amino acid type assignments could
      be made for these sharp amides using a DQF-COSY 2D-NMR experiment. The N-terminal
      15 amino acids exist as a flexible, random coil, attached to a central structure.

PMID- 8251071
TI  - The effect of placement of tryptophan residues in selected A-chain positions on
      the biological profile of insulin.
AB  - In continuation of our efforts to study the solution structure and conformational
      dynamics of insulin by time-resolved fluorescence spectroscopy, we have
      synthesized and examined the biological activity of five insulin analogues in
      which selected naturally occurring residues in the A-chain have been replaced
      with the strongly fluorescent tryptophan residue. The potency of these analogues
      was evaluated in lipogenesis assays in isolated rat adipocytes, in receptor
      binding assays using rat liver plasma membranes, and in two cases, in receptor
      binding assays using adipocytes. [A3 Trp]insulin displays a potency of 3% in
      receptor binding assays in both liver membranes and in adipocytes, but only 0.06%
      in lipogenesis assays as compared to porcine insulin. [A10 Trp]insulin displays a
      potency of ca. 40% and ca. 25% in rat liver receptor binding and lipogenesis
      assays, respectively. [A13 Trp]insulin displays a potency of ca. 39% in rat liver
      receptor binding assays, but only ca. 9% in receptor binding in adipocytes; in
      lipogenesis assays, [A13 Trp]insulin displays a potency of ca. 12%, comparable to
      its potency in adipocyte receptor binding assays. [A15 Trp]insulin exhibits a
      potency of 18% and 9% in rat liver receptor binding and lipogenesis assays,
      respectively. The doubly substituted analogue, [A14 Trp, A19 Trp] insulin,
      displays a potency of ca. 0.7% in both rat liver receptor binding assays and
      lipogenesis assays.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251072
TI  - Summary of institutional actions affecting breastfeeding.
AB  - It seems appropriate for the lactation consultant to be the advocate for infants
      and children. We must act ourselves if we want change to occur. When individuals
      cause even small changes to be made, the cumulative effect can be profound.

PMID- 8251073
TI  - Breastfeeding support for hospital employees.

PMID- 8251074
TI  - Drug information centers in the United States.

PMID- 8251075
TI  - Human milk for premature infants: an important health issue.

PMID- 8251076
TI  - Unmarried wet-nurses. 1859.

PMID- 8251077
TI  - Breastfeeding promotion in an urban New Jersey WIC office.

PMID- 8251078
TI  - Last resort help-seeking and breastfeeding failure.

PMID- 8251079
TI  - The Baby Friendly Hospital Initiative: US activities.

PMID- 8251080
TI  - ILCA's position paper statement on HIV.

PMID- 8251081
TI  - HMBANA guidelines on breast pumps and human milk storage and handling.

PMID- 8251082
TI  - NMAA policy on formula company production/sponsorship of breastfeeding
      information.

PMID- 8251083
TI  - Breastfeeding during pregnancy.
AB  - Questionnaire data were gathered on the experiences of 57 women who were
      concurrently pregnant and breastfeeding. Respondents provided information on
      nursing and weaning patterns, informational and emotional support, and pregnancy
      history. The main reasons given for continued breastfeeding after conception were
      the emotional needs of the child or child-led weaning. Forty-three percent of the
      children continued to breastfeed throughout the pregnancy and tandem nurse after
      the birth. Mothers who initiated weaning cited breast and/or nipple pain as the
      principal reason. Most weanings initiated by the children occurred during the
      second trimester, corresponding with the diminution of breastmilk. The infants
      born to these mothers were healthy and appropriate for gestational age.

PMID- 8251084
TI  - Assisting the breastfeeding mother: a problem-solving process.
AB  - At the Vancouver Breastfeeding Centre (VBC), breastfeeding is facilitated through
      a process of assessment, analysis, diagnosis, care and counsel, and evaluation.
      This process is described and related to phases of breastfeeding kinetics by
      considering two presenting problems: sore nipples, and inadequate production of
      milk.

PMID- 8251085
TI  - A fresh look at the risks of artificial infant feeding.
AB  - Declining breastfeeding rates and the aggressive marketing of breastmilk
      substitutes has blurred the distinction between breastmilk and formula. Claims
      that infant formula is safe, economical, easy to use, and nutritionally complete
      are challenged in this article, the intent of which is to raise the awareness of
      health workers to the non-publicized side of infant formula. Non-proprietary,
      referenced data is provided to illustrate that formula and breastmilk are not the
      same thing, and that health outcomes of infants who consume each may be
      different. Guilt is often cited by health workers as a reason to avoid informing
      parents about the risks of artificial feeding. Suggestions are offered for
      addressing this reasoning.

PMID- 8251086
TI  - Protocol design.

PMID- 8251087
TI  - External influences on protocol design.

PMID- 8251088
TI  - Study population selection.

PMID- 8251089
TI  - Ethical considerations.

PMID- 8251090
TI  - European investigational antiepilepsy drug trials.

PMID- 8251091
TI  - Sources of variability in clinical trials of new drugs for epilepsy.

PMID- 8251092
TI  - Alternative analyses for antiepileptic drug trials.

PMID- 8251093
TI  - Handling seizure data: special problems.

PMID- 8251094
TI  - Evaluating a new protocol from the investigator's perspective.

PMID- 8251095
TI  - Study agreements and budgets.

PMID- 8251096
TI  - Preclinical testing.

PMID- 8251097
TI  - Role of the Institutional Review Board in clinical trials.

PMID- 8251098
TI  - The role of the pharmacist in investigational AED trials.

PMID- 8251099
TI  - Patient recruitment and compliance issues in clinical trials.

PMID- 8251100
TI  - Visit management: reducing unnecessary paperwork.

PMID- 8251101
TI  - Fostering the relationship between the clinical research associate and the drug
      study coordinator.

PMID- 8251102
TI  - NIH epilepsy branch trials: budgetary and practical issues.

PMID- 8251103
TI  - Preparing for an FDA audit.

PMID- 8251104
TI  - The pipeline for antiepileptic drugs.

PMID- 8251105
TI  - Clinical trials performed for the new drug approval process in the United States:
      standard methods and alternative methods.

PMID- 8251106
TI  - Antiepileptic drugs in clinical development.

PMID- 8251107
TI  - Obstacles encountered in designing antiepileptic drug trials.

PMID- 8251108
TI  - Old and new mechanisms of antiepileptic drug actions.
AB  - At the present time, between 30% and 50% of individuals with epilepsy continue to
      have seizures and among those who are considered "controlled", a good many
      unpleasant side effects are endured. It is clear that we need more and better
      antiepileptic drugs. The virtual explosion in knowledge about the cellular and
      molecular mechanisms underlying both normal and pathological reactions of the
      brain provides encouragement that we are on the right path towards developing
      new, effective and safe agents. Whether we continue to use "model-based"
      screening or "mechanism-based screening", or both, we must not go another 14
      years without the introduction of a new antiepileptic drug. The problem is too
      large, our patients are too impatient and our responsibilities are clear.

PMID- 8251109
TI  - The domestic drug regulatory process: why time is of the essence.

PMID- 8251110
TI  - Distinguishing transmembrane helices from peripheral helices by circular
      dichrosim.
AB  - The interpretation of the circular dichroism (c.d.) spectra of proteins to date
      requires additional secondary structural information of the proteins to be
      analysed (e.g., X-ray or n.m.r. data). Therefore these methods are inappropriate
      for a c.d. database whose secondary structures are unknown, as in the case of the
      membrane proteins. The Convex Constraint Analysis algorithm [Perczel, Hollosi,
      Tusnady, and Fasman (1991) Convex constraint analysis: a natural deconvolution of
      circular dichroism curves of proteins. Protein Eng. 4, 669-679] operates on a
      collection of c.d. spectral data to extract the common spectral components with
      their spectral weights. The linear combinations of these derived 'pure' c.d.
      curves can reconstruct the original data set with great accuracy. For a membrane
      protein data set, the five-component spectra so obtained from the deconvolution
      consisted of two different types of alpha-helices (the alpha-helix in the soluble
      domain and the alpha1-helix, for the transmembrane alpha-helix), a beta-pleated
      sheet, a class-C-like spectrum related to beta-turns and a spectrum correlated
      with the unordered conformation. The deconvoluted c.d. spectrum for the alpha1
      helix was characterized by a positive red-shifted band in the range 195-200 nm
      (+95,000 degrees.cm2-dmol-1), with the intensity of the negative band at 208 nm
      being slightly less negative than that of the 222 nm band (-50,000 and -60,000
      degrees.cm2.dmol-1 respectively) in comparison with the regular alpha-helix, with
      a positive band at 190 nm and two negative bands at 208 and 222 nm with
      magnitudes of +70,000, -30,000 and -30,000 degrees.cm2.dmol-1 respectively.

PMID- 8251111
TI  - Isolation and cloning of the gene from Escherichia coli encoding glutamate
      decarboxylase.
AB  - We have isolated and cloned a 4.5-kb fragment containing the structural gene of
      glutamate decarboxylase from an overproducing strain of Escherichia coli.
      Sequencing of this fragment is in progress. The time course of glutamate
      decarboxylase expression has been also investigated.

PMID- 8251112
TI  - Sequence studies on pyridoxal phosphate-dependent enzymes.
AB  - The amino acid sequences of two pyridoxal phosphate-dependent enzymes, namely
      glutamate decarboxylase and 4-aminobutyrate aminotransferase, were solved by a
      combination of direct protein sequencing and cDNA sequencing. In the case of
      glutamate decarboxylase from Escherichia coli, correct ordering of three internal
      peptides was achieved by sequencing a fragment of DNA generated by PCR. In the
      case of 4-aminobutyrate aminotransferase from pig liver, chemical studies on the
      reaction of the enzyme with a suicide inhibitor allowed a detailed description of
      the mechanism of inactivation and collection of partial sequence information on
      the protein. The sequence of the protein was completely reconstructed after
      analysis of further peptide fragments derived by proteolytic and chemical
      cleavages, with the help of the information from the cDNA-deduced sequence of pig
      brain 4-aminobutyrate aminotransferase performed by another group (Kwon, Park and
      Churchich [1992] J. Biol. Chem. 267, 7215-7216).

PMID- 8251113
TI  - mRNA-ribosome interactions.
AB  - Synthetic mRNA analogues were constructed with sequences related to the Cro
      protein mRNA from lambda-phage and prepared by T7 transcription. Each mRNA
      contained several thiouridine (thio-U) residues. The regions upstream from the
      AUG initiator codon of the mRNA were the same in all the messages, whereas in the
      downstream part the thio-U residues were placed in selected positions. These
      positions covered the region from +4 to +16 (A in the initiator AUG codon being
      defined as +1). After binding to the ribosome in the presence of initiator tRNA
      the thio-U residues were activated by u.v. irradiation and the resulting sites of
      cross-linking to 16 S rRNA and ribosomal proteins were analysed. Cross-links to
      several ribosomal proteins were identified in different types of complex. Changes
      in the conformation of the small ribosomal subunit in different initiation and
      elongation complexes are discussed.

PMID- 8251114
TI  - D-glyceraldehyde-3-phosphate dehydrogenase: pre-existent asymmetry of the
      tetramer and its functional implications.
AB  - Modification of a single arginine residue per subunit of rabbit muscle D
      glyceraldehyde-3-phosphate dehydrogenase stabilizes the tetramer in a
      conformation wherein only two active sites are capable of performing catalysis
      (oxidation of D-glyceraldehyde 3-phosphate or hydrolysis of p-nitrophenyl
      acetate). The modified enzyme exhibits half-of-the sites reactivity towards
      iodoacetate and iodoacetamide, known to be 'all-of-the-sites reagents' with the
      native enzyme. Evidence is presented supporting the model of a built-in asymmetry
      of the tetramer. The results obtained suggest that the arginine residue (probably
      Arg-231) controls the conformational transition between the asymmetric and
      symmetric states of the tetramer.

PMID- 8251115
TI  - Role of DNA topoisomerase II in chromosome dynamics in mammalian cells.
AB  - ICRF-193, a bis-(2,6-dioxopiperazine) derivative and a non-cleavable-complex
      forming-type topoisomerase II inhibitor, inhibited cell division but allowed
      cells to traverse the cell cycle, leading to the accumulation of polyploid cells
      with 8C complements or more of DNA. Analysis of the mechanism of how cell
      division is inhibited by ICRF-193 revealed that: (1) replication of DNA was
      inhibited only at terminal stages; (2) CDC2 kinase was activated and cells enter
      absence-of-chromosome-segregation ('ACS') M-phase, where chromosomes are not
      fully condensed and are not separated, but other mitotic events, such as nuclear
      envelope breakdown and cytoskeletal reorganization forming the spindle apparatus,
      take place, i.e. chromosome dynamics could be uncoupled from the other mitotic
      events which are normally co-ordinated with the former in mitosis; (3) cells
      successfully exit from mitosis to the next G1-phase to continue the cell cycle;
      (4) progression through 'ACS' M-phase appears to be lethal to the cells. All of
      these observations could be accounted for by inactivation of topoisomerase II
      activity of the cells caused by the drug. ICRF-193 was thus shown to be a
      valuable agent in elucidation of the role of topoisomerase II in genetic
      processes in vivo.

PMID- 8251116
TI  - Protein kinases and phosphatases: regulation by autoinhibitory domains.
AB  - Numerous enzymes which can be activated by allosteric ligands appear to contain
      autoinhibitory domains which, through interaction with the catalytic domains,
      maintain the enzymes in their inactive states. Binding of activator ligands
      alters the conformation of the autoinhibitory domain and neutralizes its
      inhibitory potency, thereby producing enzyme activation. Such autoinhibitory
      domains have been intensively studied in several protein kinase and phosphatases.
      This review summarizes our current understanding of these autoinhibitory domains
      in selected protein kinases and phosphatases.

PMID- 8251117
TI  - Formate dehydrogenase from methylotrophic bacterium Pseudomonas sp. 101: gene
      cloning and expression in Escherichia coli.
AB  - Using two degenerate 20- and 23-mer oligonucleotide probes, the gene encoding
      NAD(+)-dependent formate dehydrogenase (FDH) (EC 1.2.1.2) was shown to lie within
      a 3.5 kb PstI fragment of the chromosomal DNA of methylotrophic bacterium
      Pseudomonas sp. 101. A phasmid library was prepared in the lambda pSL5 vector
      with partial EcoRI-digested DNA from Pseudomonas sp. 101. The 12 clones selected
      contained three types of phasmid: lambda pFDH1, lambda pFDH2 and lambda pFDH3
      (with inserts of 15, 17.6 and 18.5 kb respectively). The inserts contained the
      same 15 kb EcoRI and 3.5 kb PstI fragments and included the complete FDH gene.
      Further subcloning of the insert resulted in plasmid pFDH2 and a 2.32 kb HindIII
      BgIII fragment. Active enzyme was expressed in Escherichia coli TG1 (pFDH2)
      strain under control of a lac promoter.

PMID- 8251118
TI  - Exploring the active site in UDP-glucose pyrophosphorylase by affinity labelling
      and site-directed mutagenesis.
AB  - UDP-glucose pyrophosphorylase catalyses the reversible uridylyl transfer from UDP
      glucose to MgPPi, forming glucose 1-phosphate and MgUTP. We have identified, by
      using uridine di- and tri-phosphopyridoxals, five lysyl residues located at or
      near the UDP-glucose-binding site. Another reactive analogue, pyridoxal
      diphosphoglucose, also modified the same set of lysyl residues. Based on the
      amounts of labels incorporated into each lysyl residue, we have provided a
      hypothetical model for possible locations of the five lysyl residues around the
      substrates bound to the enzyme. This model was consistent with the results of the
      mutagenesis studies. Lys367 is essential for the catalysis, whereas Lys263 may
      participate in the binding of PPi and/or glucose 1-phosphate in the binary
      complex. On the other hand, the results of affinity labelling with pyridoxal 5'
      diphosphate suggest the role of Lys329 in the direct interaction with PPi in the
      enzyme-UDP-glucose complex.

PMID- 8251119
TI  - A Delphi study of pediatric oncology nurses' facilitative behaviors.
AB  - Using a classic Delphi methodology, this study identified the nursing behaviors
      and interventions that oncology nurses rated as most important in facilitating
      the patient's, parents', and siblings' coping efforts with the effects of disease
      and treatment. Random selection of 300 pediatric oncology nurses resulted in a
      final sample of 69 nurses who completed all 3 rounds of the Delphi. The majority
      of the nurses were younger than 35 years of age, had less than 10 years of
      experience, were educated with at least a bachelor's degree, and practiced in an
      all-oncology setting. Twenty-eight facilitative behaviors were identified for the
      child with cancer, 25 for the parents, and 25 for the siblings. Results of this
      study support previous research on patient, parent, and sibling coping.

PMID- 8251120
TI  - A trajectory approach for education of the child/adolescent with cancer.
AB  - Survival in childhood cancer has improved, but the child's learning capability
      and psychosocial adjustment are affected by intense therapy, the side effects,
      and psychosocial issues. The resulting problems of school attendance and
      performance need to be addressed by pediatric oncology nurses. This article
      describes an education intervention program that is based on a treatment
      trajectory with interventions that occur from diagnosis through long-term
      survival and are directed toward the patient/parent, school personnel, and
      classmates. Both anecdotal and empirical evaluations of the program are being
      completed. This program provides pediatric oncology nurses with a model for
      program development and resource materials.

PMID- 8251121
TI  - Parents' perceptions of their quality of life.
AB  - The purpose of this study was to assess parents' perceptions of their quality of
      life after the diagnosis and treatment of cancer in their child. The following
      questions were addressed: (1) How do parents of children with cancer perceive
      their quality of life; (2) How do parents of children with cancer perceive their
      quality of life compared with before their child was diagnosed; and (3) Is there
      a statistically significant difference in parents' quality of life perceptions
      now as compared with before their child had cancer? Using Roy's Adaptation Model
      as a theoretical framework, a descriptive study research design was used with a
      convenience sample of 30 parents. Data collection involved parental completion of
      the Varricchio-Wright Impact of Cancer Questionnaire-Parents, a 17-item
      instrument measuring parental quality of life in each of Roy's domains, and a
      Demographic Information Form. Measures of central tendency were used to describe
      the sample and to answer the first two research questions; student's t-test was
      used to answer the third. Results indicated that this sample of parents perceived
      their quality of life now as good, but not as good as before their child was
      diagnosed with cancer. There was a statistically significant difference in
      parents' perceptions of their quality of life now and before their child was
      diagnosed with cancer. The significance of this study related to nursing practice
      and research is discussed and recommendations for future research are given.

PMID- 8251122
TI  - Waiting and not knowing: the diagnosis of cancer in a child.
AB  - A subset of data from a longitudinal grounded theory study was analyzed to
      describe the experience families have during the period immediately surrounding
      the time of diagnosis of cancer in a child. A convenience sample consisted of 40
      members of seven families with a child who was recently diagnosed with cancer
      with a favorable prognosis. All family members 5 years of age and older
      participated. Data collection consisted of three tape-recorded, semistructured
      interviews with family members in the home. It was found that the "waiting and
      not knowing" of this period was most distressing for family members. This period
      is further described and implications for nursing practice are discussed. Factors
      limiting generalizability of the findings include the small sample size, single
      site, and the short length of time families were followed.

PMID- 8251123
TI  - Research design: descriptive research.

PMID- 8251124
TI  - Methotrexate.

PMID- 8251125
TI  - C-H...O packing motifs in some cyclopenta[a]phenanthrenes.
AB  - An analysis has been made of the C-H...O interactions in
      cyclopenta[a]phenanthrenes, for which structural data on fifteen 15,16
      dihydrocyclopenta[a]-phenanthren-17-ones are available. These compounds mostly
      contain only one O atom, a carbonyl group at the 17-position, and therefore the
      only groups available for interactions are C-H groups. In addition, the crystal
      structure of a second polymorph of the 11-ethyl derivative is described. M(r) =
      260.33, Pbca, a = 17.012 (2), b = 21.042 (2), c = 7.6465 (6) A, V = 2737.2 (4) A,
      Z = 8, Dx = 1.264 Mg m-3, Cu K alpha, lambda = 1.5418 A, mu = 0.56 mm-1, F(000) =
      1104, T = 295 K, final R = 0.090 for 1669 reflections above 2 sigma (F). The
      conformation of the ethyl group is gauche [C(12)-C(11)-C(18)-C(19) = 75.8 (7)
      degrees], differing from the cis value of -1.3 (5) degrees for the Pnaa form. The
      molecular distortion in the Pbca polymorph is also larger than that in the Pnaa
      polymorph; this distortion is evidenced by torsion angles (13-20 degrees) in the
      bay region and by an out-of-plane displacement (0.8 A) of the C atom of the
      methylene portion of the ethyl group [the C atom attached to C(11)]. Packing
      diagrams and intermolecular distances were analyzed for all the
      dihydrocyclopenta[a]phenanthrenes for which structural data are available. There
      appear to be three types of packing. The first type consists of a dimer
      herringbone formed by the interactions of two molecules by way of the ketone
      group and the C-H of C(12) of the adjacent ring. The second type of packing also
      involves a dimer but involves C-H and O-C groups at either ends of the molecule.
      The third type is a layer structure and involves compounds that crystallize with
      a unit-cell length of 7.5-7.6 A (or, in a very planar structure, 13.8 A). The
      translational stacking (approximately 4 A apart) found in polycyclic aromatic
      hydrocarbons is not observed in the crystal structures of these
      dihydrocyclopenta[a]-phenanthrenes because of the bulk of methyl or methylene
      groups and the dipole moment of the carbonyl group.

PMID- 8251126
TI  - Improved heart equipment contract.

PMID- 8251127
TI  - Artificial pancreas on trial in USA.

PMID- 8251128
TI  - Japan--artificial heart powered externally.

PMID- 8251129
TI  - FDA approval for polyester catheter cuff.

PMID- 8251130
TI  - Immunosensor for extra-lab measurements based on liposome amplification and
      capillary migration.
AB  - A novel prototype immunosensing device has been developed which incorporates the
      simplicity of competitive immunochromatography with the rapid signal
      amplification capabilities of marker-loaded liposomes. An avidin capture zone
      provides direct readout of the analyte concentration.

PMID- 8251131
TI  - Enzyme activation for activator and enzyme activity measurement.
AB  - A new sensing principle of enzyme activation is demonstrated for the
      determination of glycogen phosphorylase b and its allosteric effector AMP. As the
      indicator of the phosphorylase catalysed glycogen phosphorolysis, glucose-1
      phosphate formation has been detected with an enzyme sequence comprising
      coentrapped alkaline phosphatase, mutarotase and glucose oxidase on a hydrogen
      peroxide indicating electrode. The optimized three-enzyme sensor was useful for
      the determination of 0.005-0.2 U.ml-1 glycogen phosphorylase a and b. A biosensor
      for AMP and inorganic phosphate has been developed by coupling glycogen entrapped
      phosphorylases to the three-enzyme indicator membrane. The measurement of AMP is
      based on the modulation of the phosphorylase b catalysed glycogen phosphorylating
      activity. The proposed sensor responds to AMP between 5 and 150 microM. The
      calibration graph of the reagentless phosphate sensor is linear between 0.05 and
      1 mM.

PMID- 8251132
TI  - In vivo experiment with the electrocatalytic glucose sensor in sheep.
AB  - In order to control the insulin dosage in diabetes therapy, an electrocatalytic
      glucose sensor for long-term implantation has been developed. To test the sensor
      function over a longer period, it was implanted as a flow-through cell in a
      sheep. The sensor was inserted into the carotid artery and driven by a portable
      electronic unit worn by the animal. The blood flow characteristics were nearly
      constant over the whole period of measurement. We were able to verify the sensor
      performance in one experiment lasting over 71 days. Stable calibrations of the
      sensor were achieved over longer periods of time, so that only a few calibrations
      are necessary in monitoring the blood glucose level during the whole period of
      implantation. It was thus possible to set up a calibration which was valid over
      33 days (mean error 2.5 mM). These calibrations were not adversely affected by
      host reactions. The cross-sensitivity of the sensor was also verified, and it was
      found that the tested molecules did not significantly affect the sensor function.
      Only high concentrations of lactate and ethanol require a special adaptation of
      the calibration to suppress their influence. The sensor will be further improved
      to obtain a still longer calibration stability, and adapted for animal
      implantation, thus making it useful for clinical application.

PMID- 8251133
TI  - Biosensor for direct determination of glucose and lactate in undiluted biological
      fluids.
AB  - This paper describes the implementation of a bienzyme sensor for the direct
      determination of glucose and lactate in undiluted biological samples. The
      biosensor exploits the competitive action versus the substrate itself by two
      different enzymes immobilized into a sandwich of two different membranes. In this
      way the quantity of substrate reaching the indicating electrode is reduced and
      this determines an extension of the linearity range.

PMID- 8251134
TI  - Novel approaches for the use of mediators in enzyme electrodes.
AB  - This work describes the preparation of glucose electrodes consisting of an enzyme
      (glucose oxidase) and a mediator embedded in a colloidal graphite emulsion
      matrix. These components are homogeneously mixed in an organic medium that
      evaporates rapidly while the enzyme activity remains intact. The appropriate
      conditions for preparation and measurement, as well as electrochemical
      characterization of these electrodes, are discussed. The problem of mediator
      leaching in electrodes using vinyl ferrocene was overcome by the use of a special
      membrane that prevented leaching of positive ferricinium ions by electrostatic
      repulsion under the appropriate measurement conditions, including minimal
      exposure of the electrode to anodic potentials, thus increasing the long-term
      stability. The resulting electrodes are easily prepared, have fast and high
      response independent of oxygen tension and can be stored in dry form. The linear
      range can be extended by the introduction of a dialysis membrane and can thus be
      adjusted to the measurement of glucose concentration in the range of medical
      interest.

PMID- 8251135
TI  - An optical hydroxyl radical sensor.
AB  - A hydroxyl radical (.OH) fibre-optic sensor has been developed. An .OH radical
      sensitive reagent phase (nitrophenol) was immobilized onto XAD-7 methacrylate
      beads. Subsequently the beads were attached to the distal end of a
      polymethylmethacrylate fibre optic. Nitrocatechol, generated from the attack of
      .OH radical on nitrophenol, exhibits a strong absorption band in the visible
      region of the electromagnetic spectrum (lambda max = 510 nm). Here, reflectance
      spectroscopy was employed to monitor the concomitant intensity decrease in the
      reflectance spectrum upon .OH radical attack. The sensor exhibited excellent
      stability and linearity of response to .OH generated by a Fenton reaction system
      (EDTA, Fe(II) and H2O2) with H2O2 over the concentration range of 3.6 x 10(-6)
      8.0 x 10(-2) M.

PMID- 8251136
TI  - A carrageenan hydrogel stabilized colloidal gold multi-enzyme biosensor electrode
      utilizing immobilized horseradish peroxidase and cholesterol oxidase/cholesterol
      esterase to detect cholesterol in serum and whole blood.
AB  - The preparation of two immobilized enzyme electrodes is described. One electrode
      contains horseradish peroxidase absorbed to colloidal gold and deposited on a
      glassy carbon electrode along with cholesterol oxidase entrapped in a carrageenan
      hydrogel. The second electrode also includes cholesterol esterase entrapped in
      the carrageenan. The incorporation of ferrocene or ferrocenecarboxylic acid
      mediator is brought about by either evaporation on the glassy carbon electrode
      or, in the latter case, entrapment in the carrageenan hydrogel. Amperometric
      signal generation results from the HRP catalyzed turnover of H2O2, a secondary
      product of the cholesterol oxidase catalyzed oxidation of cholesterol. Use of
      these enzyme electrodes makes cholesterol detection possible in human serum, low
      density lipoprotein, and whole blood.

PMID- 8251137
TI  - Studying the bienzyme reaction with amperometric detection for measuring maltose.
AB  - If a fermentation process is followed by a change in the concentration of
      maltose, information on the level of the maltose is important. A new type of
      sensor was developed for measuring the content of maltose in fermentation broth.
      The base of the sensor is a thin-layer reactor, in which a protein membrane was
      chosen for the immobilization of enzymes. To measure maltose, we investigated the
      influence of enzymes such as alpha-glucosidase (EC 3.2.1.20) and amyloglucosidase
      (EC 3.2.1.3) on the effectiveness of conversion to glucose. Because
      amyloglucosidase proved to be more effective, a mixture of amyloglucosidase and
      glucose oxidase was applied for the determination of maltose. To develop the best
      measuring technique, the consequences of changes in different parameters, such as
      the optimal ratio of enzymes, role of pH value and that of the flow rate, were
      studied. An amperometric measuring cell with Pt-Ag/AgCl-Pt electrodes was used at
      +600 mV operating potential. The results indicate that the maltose content in
      different types of fermentation broth can be determined by the new measuring cell
      in the range of 0.2-4 mM maltose. The cell was successfully tested in the
      fermentation of brewer's yeast.

PMID- 8251138
TI  - Bioactive peptides in food.

PMID- 8251139
TI  - Nuclear weapons testing and childhood leukaemia.

PMID- 8251140
TI  - Triglyceride-rich lipoproteins and atherosclerosis, from fast to feast.
AB  - There is increasing evidence that fasting hypertriglyceridaemia identifies
      individuals who are at increased risk for coronary artery disease. It is probable
      that this reflects the effects of the smaller triglyceride-bearing lipoproteins.
      It may also reflect increased levels of postprandial lipoproteins. There is
      considerable theoretical and experimental evidence to support an atherogenic role
      for the smaller, triglyceride-rich postprandial lipoproteins. Cross-sectional
      studies in humans also indicate that those with coronary disease have increased
      levels of postprandial lipids, probably in the remnants of chylomicrons. Recently
      we have completed a study examining the progression of coronary atherosclerosis
      angiographically. The study showed that the progression was linearly related to
      the numbers of chylomicron remnant particles, as reflected by the quantity of
      apoB48 in Sf20-60 lipoproteins, in the postprandial circulation. This paper
      reviews these studies, the physiology of postprandial lipoprotein metabolism and
      the therapeutic implications of this information.

PMID- 8251141
TI  - Heterogeneity in Alzheimer's disease.
AB  - The genetic data implicating mutations framing the beta-amyloid segment of the
      amyloid precursor protein as causes of Alzheimer's disease are reviewed and
      integrated with information on the normal processing of the amyloid precursor
      protein. The data indicating that there is a second and quantitatively major
      locus for early-onset Alzheimer's disease on the long arm of chromosome 14 are
      reviewed. The prediction that this second genetic locus will produce a protein
      intimately involved in the metabolism of the amyloid precursor protein is
      reiterated, together with the prediction that all causes of Alzheimer's disease
      will directly involve this process.

PMID- 8251142
TI  - Mechanisms of herpes virus resistance.
AB  - The introduction of virus-specific anti-herpes virus agents such as acyclovir,
      ganciclovir and Foscarnet has had a significant impact on the management of
      herpes virus infections. The use of specifically acting antimicrobial agents,
      however, raises the question of drug resistance. Exposure in cell culture of
      herpes virus to these agents results in the selection of drug-resistant variants,
      with resistance being due to alterations in the genes encoding the target enzymes
      involved in the mechanism of action of the drugs concerned, e.g. in the case of
      acyclovir resistance occurs as a result of deletions or alterations in the
      thymidine kinase (TK) or alterations in DNA polymerase genes. Pathogenicity
      studies reveal that drug-resistant variants are disadvantaged, in particular the
      TK deletion variants which are less pathogenic and unable to reactivate from
      latent infections. Extensive studies in cell culture and animal models with
      herpes viruses have provided an understanding of the mechanisms of resistance and
      more recently these findings have been correlated with the clinical experience.
      The incidence of virus resistance in immunocompetent patients is extremely rare,
      whereas resistance has infrequently been reported in immunocompromised
      individuals where exposure to drug is prolonged. However, the understanding of
      the mechanisms and consequences of virus resistance gained in cell culture and in
      animal models has led to the successful management of resistant episodes in the
      clinic, either by temporary removal of the selection pressure or by providing
      alternative therapies.

PMID- 8251143
TI  - Deep vein thrombosis and occult cancer.
AB  - In contrast to the established relation between known cancer and subsequent
      venous thromboembolism, the question of whether an association exists between
      venous thrombosis and the risk of subsequent overt cancer has remained without a
      convincing answer until 1992. A recent publication has provided a firm
      demonstration of this connection. Although this study has demonstrated a highly
      significant association between idiopathic vein thrombosis and subsequent overt
      malignant disease, firm recommendations for an extensive screening of cancer in
      all such patients cannot be made on the basis of these results.

PMID- 8251145
TI  - Low-molecular-weight heparins for the treatment of venous thromboembolism.
AB  - Recent studies have indicated that certain low-molecular-weight heparins given
      subcutaneously may replace continuous intravenous unfractionated heparin for the
      treatment of venous thromboembolism. Low-molecular-weight heparins have a
      predictably high absorption rate when given subcutaneously and they do not
      require laboratory monitoring. These characteristics of low-molecular-weight
      heparin therapy raise the possibility of treating uncomplicated patients with
      deep venous thrombosis or pulmonary embolism in the outpatient setting. The
      advantages to the patient of avoiding in-hospital care and its associated hazards
      are obvious. Outpatient low-molecular-weight heparin will likely prove to be
      highly cost-effective. At the present time, the finding associated with an
      individual low-molecular-weight heparin preparation cannot be extrapolated to
      different low-molecular-weight heparins and each must be evaluated in separate
      clinical trials. Recent randomized clinical trials indicate that low-molecular
      weight heparin may be safer and more effective than continuous intravenous
      unfractionated heparin in the treatment of proximal venous thrombosis. A
      decreased mortality rate, which was particularly striking in patients with
      metastatic carcinoma, was unexpected and requires confirmation in further
      prospective randomized trials.

PMID- 8251144
TI  - Therapy of penicillin- and cephalosporin-resistant pneumococcal infections.
AB  - Streptococcus pneumoniae has recently developed resistance to almost every agent
      that has been used for therapy, including the extended-spectrum cephalosporins.
      The empiric therapy of penicillin-resistant pneumococcal meningitis should
      include cefotaximine or ceftriaxone plus vancomycin pending cephalosporin
      susceptibility results. Intermediate penicillin-resistant pneumococcal infections
      outside the central nervous system will usually respond to high dose intravenous
      beta-lactam antibiotic therapy. Highly penicillin-resistant pneumococcal
      infections may not respond to penicillin therapy, in which case therapy with
      vancomycin, imipenem or a macrolide (if susceptible) can be considered.
      Pneumococcal resistance to commonly used oral agents varies geographically and
      the efficacy of a particular agent can only be assured once the infecting strain
      is known to be susceptible. It is imperative to determine the susceptibility of
      every pneumococcal isolate to the agent(s) being used for therapy, particularly
      in cases of meningitis and to document rapid sterilization of infected body sites
      or fluids.

PMID- 8251146
TI  - Preimplantation diagnosis of genetic disease.
AB  - If a couple is known to be at risk of transmitting a severe genetic disease to
      their offspring, the fetus may be tested by chorionic villus sampling or
      amniocentesis during pregnancy. If the fetus proves to be affected, the couple
      has the option of terminating the pregnancy. Recently, an alternative approach
      has been developed, i.e. to screen embryos produced by in vitro fertilization
      before implantation. Diagnostic analysis is carried out on a single cell removed
      by micromanipulation from the 8-cell embryo or on the polar body from the
      unfertilized egg. Preimplantation diagnosis is now a feasible alternative to
      screening during pregnancy and may be the preferred route for some couples.

PMID- 8251147
TI  - Antibiotics in pregnancy--a prospective cohort study on the policy of antibiotic
      prescription.
AB  - Pregnancy is associated with special problems with respect to antibiotic
      selection and dosage due to potential teratogenic or toxic effects on the fetus
      by the drug itself, and the great physiological adjustments in the mother. This
      survey was designed to record the use of antibiotics and the policy of
      prescription of antimicrobial drugs during the course of pregnancy. In total,
      4055 pregnant women residing in a county in south-western Finland during the
      period June 15, 1987-June 14, 1988 were studied. Penicillin, erythromycin and
      pivmecillinam were the most often used antibiotics during pregnancy comprising
      together 65.4% of all antibiotic use; 94.1% of all antimicrobial medication was
      administered orally. The highest incidence for antibiotic use (45.4% of all) as
      well as for treated infections (45% of all) was at the second trimester. The
      duration of medication was commonly 10 days (44.4%, SD 14.6) or 7 days (27.9%, SD
      7.7). Penicillin was in a few cases prescribed at increased dosage (25.6%), while
      erythromycin and amoxicillin were occasionally administered at reduced dosages
      (30.2% and 42.5%, respectively). The dosages should probably be individualized
      more often, according to the information available on the pharmacokinetics of
      specific antibiotics during pregnancy. It may also be possible to reduce the
      length of antibiotic treatment for UTI.

PMID- 8251148
TI  - Basics in psychoneuroimmunology.
AB  - Central nervous, endocrine and immune systems (IS) are all considered to be
      important regulators of psychological and physical wellbeing. Research into
      psychoneuroimmunology became relatively widespread in the 1970s. More and more
      studies considered these systems to be interactive units. Disciplines ranging
      from anatomy to psychology revealed the IS as the target of brain and endocrine
      signals. Findings also suggest that the IS is active even in a bidirectional
      feedback loop. Today the IS is no longer regarded as autonomous and scientists
      begin to see the emergence of a new psychosomatic paradigm. So far, evidence for
      the mind-body interaction paradigm has been collected with regard to the role of
      nerve fibres in lymphatic tissues, the effects of brain lesions on the IS, the
      interplay of neurotransmitters, hormones and immunotransmitters in a network of
      bidirectional feedback loops between the brain and the IS, the effects of
      ontogeny, learning and conditioning on the development of the IS, the impact of
      experimental and naturally occurring stressors on the IS, the possible immune
      modulating effects of personality characteristics, life style and psychodynamic
      processes and the role of the IS in disease. Research findings in most of the
      mentioned topics are presented.

PMID- 8251149
TI  - Depression, adrenal steroids, and the immune system.
AB  - During the past decade, over 30 studies have examined the immune system in
      depression. While a number of investigators have reported depression-related
      alterations in peripheral blood immune cell number and function, many researchers
      have been unable to replicate these findings. The relationship between depression
      and the immune system has turned out to be much more complex than was initially
      anticipated. Factors which have complicated the interpretation of the research
      include the heterogeneity of depressed patients, the variability of immune
      assays, and the clinical relevance of these assays. In this review we conclude
      that alterations in the immune system do not appear to be a specific or
      reproducible biological correlate of depression but may occur in association with
      other variables which characterize depressed patients including age, sex and
      severity of depression. Conceptual frameworks for future research on the immune
      system and depression are discussed and include: (i) depression as a cofactor in
      the development, course and outcome of diseases involving the immune system; (ii)
      depression as a neuroimmunological disease; and (iii) depression as a model for
      studying neuroendocrine-immune interactions in humans. In terms of this third
      line of research, patients with depression consistently have been shown to
      display abnormalities in the secretion of adrenal steroids, and new data is
      presented which indicates that adrenal steroids may play a much more complex role
      in the modulation of the immune response than has been previously appreciated.

PMID- 8251150
TI  - Autoimmunity in schizophrenia: a review of recent findings.
AB  - The pathophysiology of psychotic and other symptoms in schizophrenia remains a
      mystery despite decades of research. Even though it has been suspected for many
      years that autoimmune mechanisms may play a role in the pathophysiology of
      schizophrenia, firm evidence for this hypothesis has been lacking. Our studies,
      over the last 10 years, have revealed that a subgroup of schizophrenics have
      several significant immunological abnormalities, including increased prevalence
      of autoimmune diseases and of antinuclear antibodies (ANA) and anticytoplasmic
      antibodies (ACA), decreased lymphocyte interleukin-2 (IL-2) production, increased
      serum IL-2 receptor concentration, increased serum IL-6 concentration, and an
      association with HLA antigens. These findings are characteristic of autoimmune
      diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis and
      insulin-dependent diabetes mellitus. We also found that some schizophrenics have
      antibodies to hippocampal antigens (AHA) in their serum, together with lowered IL
      2 production. None of the above findings can be interpreted as definitely
      confirming the role of autoimmunity in schizophrenia. Nevertheless, taken
      together, the recent evidence points towards the existence of a subgroup of
      schizophrenics who have immunological findings consistent with that hypothesis.
      Further studies directed at finding the brain antigens targeted by the immune
      system in these patients, and longitudinal studies correlating clinical and
      immune changes over time, are needed.

PMID- 8251151
TI  - Schizophrenia: prenatal influenza and autoimmunity.
AB  - The schizophrenic syndrome may represent a stereotyped response by the developing
      brain to various insults, including micro-organisms. We review studies that have
      examined the association between schizophrenia and infectious agents, and examine
      the current evidence for the hypothesis that exposure to influenza during fetal
      life increases the risk of later schizophrenia. A prenatal autoimmune basis for
      some cases of schizophrenia is proposed.

PMID- 8251152
TI  - A reliable protocol for dsDNA and PCR product sequencing.

PMID- 8251153
TI  - An alternate universal forward primer for improved automated DNA sequencing of
      M13.

PMID- 8251154
TI  - Simplifying detection of microsatellite length polymorphisms.

PMID- 8251155
TI  - An improved method for rapid screening of DNA mutations by nonradioactive single
      strand conformation polymorphism procedure.

PMID- 8251156
TI  - Direct selection of positive recombinant clones by PCR.

PMID- 8251157
TI  - Soft agar cloning with antibody overlay to identify Chinese hamster ovary clones
      secreting recombinant products.

PMID- 8251158
TI  - Rapid transformation of cryopreserved competent Schizosaccharomyces pombe cells.

PMID- 8251159
TI  - A rapid screening method for bacteria containing firefly luciferase plasmids.

PMID- 8251160
TI  - Rapid purification of bacteriophage lambda DNA.

PMID- 8251161
TI  - Purification of cloning quality lambda gt11 DNA.

PMID- 8251162
TI  - Double-reporter vectors for studying bidirectional gene transcription.

PMID- 8251163
TI  - Improved proteinase K digestion for the rapid isolation of mRNA from mammalian
      tissues.

PMID- 8251164
TI  - Optimization of the resolution of phosphoamino acids by one-dimensional thin
      layer electrophoresis.

PMID- 8251165
TI  - Excess of PCR primers inhibit DNA cleavage by some restriction endonucleases.

PMID- 8251166
TI  - A rapid and quantitative DNA sex test: fluorescence-based PCR analysis of X-Y
      homologous gene amelogenin.
AB  - A rapid, simple and reliable sex test that entails PCR amplification of a segment
      of the X-Y homologous gene amelogenin has been developed. We used a single pair
      of primers spanning part of the first intron which generated 106-bp and 112-bp
      PCR products from the X and Y homologues, respectively, that can be analyzed
      simply by agarose gel electrophoresis. Less than 1 ng of template DNA is required
      for gender assignment, and the test has been automated by the fluorescent tagging
      of the PCR products that are then quantitated during electrophoresis by automated
      fluorescence-detection technology. Quantitation enables sex chromosome aneuploidy
      to be determined, and the amelogenin intron sequence can also be co-amplified
      with several highly polymorphic microsatellite loci, thereby providing a combined
      gender/identity DNA test.

PMID- 8251167
TI  - Nonradioactive gel mobility shift assay using chemiluminescent detection.
AB  - A nonradioactive gel mobility shift assay using chemiluminescent detection
      following semidry transfer to nylon membranes is described. The procedure
      utilizes digoxigenin-labeled oligonucleotides in conjunction with anti
      digoxigenin antibody Fab fragments coupled to alkaline phosphatase. Detection of
      alkaline phosphatase is by autoradiography of the chemiluminescence produced
      during enzymatic dephosphorylation of a dioxetane substrate. This method offers
      similar sensitivity to radioactive methods while having the advantages of
      multiple exposures, faster processing, stability of labeled oligonucleotides and
      safety associated with nonradioactive methods of detection.

PMID- 8251168
TI  - One-step insertion of oligonucleotide linkers or adapters to DNA using
      unphosphorylated oligonucleotides.
AB  - A simple and efficient method was developed for insertion of oligonucleotide
      sequences into plasmids. In this method, an unphosphorylated oligonucleotide was
      ligated to the restriction-digested phagemid DNA. Only the single strand of the
      oligonucleotide was ligated at the 5' end of the phagemid, and this resulted in
      the creation of a long self-complementary single-strand overhang. These single
      strand overhang-possessing phagemids were used to transform XL-1 cells. This
      simple ligation and transformation reaction rendered approximately 7.5 x 10(4) to
      5 x 10(5) of white colonies per microgram DNA from the isopropyl-beta-D
      thiogalactopyranoside and 5-bromo-4-chloro-3-indolyl-beta-D-galacto-pyranoside
      plate. This number is almost the same or even higher than the number of blue
      colonies from the control reaction in which ligase was used without the
      oligonucleotide. By this method we could mutate one enzyme site to another or
      create ribozyme and substrate phagemid very easily. Fidelity of this method was
      checked by restriction digestion, DNA sequencing and ribozyme reaction. By DNA
      sequencing, we observed that 100% of the white colonies contained a single
      oligonucleotide sequence.

PMID- 8251169
TI  - Funnel-well SDS-PAGE: a rapid technique for obtaining sufficient quantities of
      low-abundance proteins for internal sequence analysis.
AB  - We report a modified sodium dodecyl sulfate polyacrylamide gel electrophoresis
      method that permits up to a 60-fold concentration factor, without significant
      loss of protein. This method leads to very efficient concentration of low
      abundance proteins from partially purified fractions or very dilute protein
      solution. Furthermore, it permits in situ enzymatic digestion and consequently
      increases the probability of obtaining a suitable internal sequence.

PMID- 8251170
TI  - Pilot-scale production of murine monoclonal antibodies in agitated, ceramic
      matrix or hollow-fiber cell culture systems.
AB  - The purpose of this research was to compare three bioreactor systems for the
      pilot-scale production of monoclonal antibodies (MAbs). We needed to produce gram
      quantities of murine MAbs against human prostatic acid phosphatase for use in
      fragmentation, radiolabeling and in vivo radio-imaging studies. The stable
      hybridoma cell line secreting IgG1 antibodies was chosen for production. Of the
      available bioreactor systems, we chose to test an agitating 30-liter bioreactor
      in repeated batch mode, a ceramic-matrix bioreactor in both repeated batch and
      continuous perfusion modes and a hollow-fiber bioreactor in continuous perfusion
      mode. The highest cultured MAb yield, 151 +/- 126 mg/day (mean +/- SD, n = 22),
      was achieved in the 30-liter bioreactor in repeated batch mode with the MAb being
      harvested in a large volume of medium, giving a reactor productivity of 4.3 +/
      3.4 mg/liter/day (mean +/- SD, n = 22). The most concentrated MAb was harvested
      from the continuously perfused hollow-fiber bioreactor, which had the highest
      reactor productivity, 307 +/ 142 mg/liter/day (mean +/- SD, n = 47) and an
      average rate of MAb production of 55.3 +/- 25.7 mg/day (mean +/- SD, n = 47).
      Taking the use of serum into consideration, the cost of MAb production was lowest
      in the continuously fed and harvested ceramic-matrix and hollow-fiber cell
      culture systems. A compact blood glucose meter proved to be a novel and suitable
      device for the rapid monitoring of glucose concentrations in hybridoma cultures.

PMID- 8251171
TI  - Efficacy of fluorescence-based PCR-SSCP for detection of point mutations.
AB  - We assessed the efficiency of fluorescence-based PCR single-strand conformation
      polymorphism analysis (PCR-SSCP) using an automated DNA sequencer and analysis
      software. We evaluated 48 point mutations in a 191-bp stretch of mouse beta
      globin. The mutations included 10 transversions and 38 transitions; and both
      types of mutation were compared at six different locations in the PCR fragment.
      Mobilities of the red dye-labeled internal standard fragments were non
      proportional to size but highly reproducible and were used to normalize or
      correct minor differences in apparent electrophoretic mobility between lanes.
      Forty-six of forty-eight mutants (96%) were distinguished from wild type when run
      in separate lanes using one set of conditions. Co-electrophoresis of wild type
      and mutant in the same lane resolved 100% of 45 mutants from wild type. Under
      conditions of this study, the magnitude of mobility shifts resulting from the
      globin mutations were largely determined by position of the mutation, rather than
      by the nature of the substitution (transition vs. transversion). However,
      examination of paired mutations at the same position revealed that some
      substitutions cause greater mobility shifts than others.

PMID- 8251172
TI  - A rapid method for site-specific mutagenesis using larger plasmids as templates.
AB  - To facilitate the introduction of specific point mutations in plasmids that are
      too large to be amplified efficiently by a single PCR, we have developed a method
      for site-directed mutagenesis by generating partial plasmid fragments, which
      introduces changes as simply as conventional techniques. Plasmids containing a
      fragment of the human immunodeficiency virus type-1 (HIV-1) envelope gene were
      subjected to PCR with four pairs of PCR primers for each desired point mutation.
      One primer in each of two of these four pairs contained the desired mutation. The
      four pairs of primers were designed so that four overlapping fragments were
      amplified from the plasmid template, two of which contained the mutation. These
      fragments were then reannealed and electroporated directly into Escherichia coli.
      The desired mutation was typically found in 66% to 83% of the resulting colonies.
      The technique is almost as simple as previous techniques, shows similar
      efficiency and is applicable to plasmids that would normally be too large for
      efficient site-specific mutagenesis. The entire procedure, from PCR amplification
      to transfection into E. coli, can be completed in one day.

PMID- 8251173
TI  - The vitamin D-binding protein gene: quantitation of amplified nucleic acids by
      ELISA.
AB  - We have utilized enzyme-linked immunosorbent assay (ELISA) to quantitate PCR
      amplified DNA. This method was used to measure mRNA for the vitamin D-binding
      protein (Gc), beta-actin and the transferrin receptor (TR) gene in the Hep3B cell
      line. Total RNA from Hep3B cells was reverse transcribed to obtain cDNA, which
      was amplified in the presence of digoxigenin-dUTP by PCR. The PCR products were
      then hybridized in liquid phase to a biotinylated, nested capture probe for the
      respective sequences. The hybridized products were bound to a streptavidin-coated
      ELISA plate and were detected by an alkaline-phosphatase-conjugated antibody to
      digoxigenin. ELISA standard curves for Gc and control genes, beta-actin and TR,
      were obtained after PCR amplification of serial dilutions of Hep3B total RNA. As
      an external standard, an ELISA standard curve for Gc was obtained after PCR
      amplification of serial dilutions of a full-length Gc cDNA insert obtained from a
      recombinant plasmid. Thus, we were able to develop a non-isotopic quantitation
      assay for PCR-amplified DNA that is highly sensitive and has the specificity of
      hybridization-based methods.

PMID- 8251174
TI  - Automated low-redundancy large-scale DNA sequencing by primer walking.
AB  - Low-redundancy automated DNA sequencing by primer walking is described. T7 DNA
      polymerase is used together with computer-selected walking primers and
      fluorescein-dATP as internal label to sequence large plasmids or cosmids directly
      on a standard DNA sequencer with an error rate below 1% up to 500 bases (in the
      unedited raw data). The low error rate allows efficient sequencing with low (2-3
      times) redundancy. Plasmid subclones covering 20 kb of a cosmid insert were
      sequenced with an overall redundancy of 2.7 in the course of the European
      community Saccharomyces cerevisiae genome sequencing project. Neighboring plasmid
      subclones were linked by direct cosmid sequencing. Sets of ten walking primers
      are synthesized on the EMBL multiple segmental DNA synthesizer at low costs and
      used for sequencing with greater than 95% efficiency. The accuracy of the
      directed approach is improved by simultaneous walking on both strands by
      designing two primers in opposite directions in the same starting region. One
      primer is used to confirm sequence data on the opposite strand, and the other
      primer to obtain new sequence data.

PMID- 8251175
TI  - Quantitation of genomic methylation using ligation-mediated PCR.
AB  - We have developed a new technique for the quantitation of CpG methylation of
      genomic DNA. This method measures the conversion of a larger amplified DNA
      fragment to a shorter DNA product correlating with demethylation. The procedure
      uses pairs of non-isoschizomeric enzymes, one of which is methylation-sensitive,
      to cleave genomic DNA at closely spaced sites. The extent of cleavage by the
      methylation-sensitive restriction enzyme is quantitated by amplification of these
      digestion products with ligation-mediated PCR and radioactive labeling of the
      product. The ratio of the two amplified fragments correlates with the degree of
      methylation at the restriction site. The analysis is rapid, quantitative,
      internally controlled and requires small quantities of genomic DNA.

PMID- 8251176
TI  - A versatile ELISA-PCR assay for mRNA quantitation from a few cells.
AB  - Gene expression studies require a sensitive and quantitative assay of mRNA
      amounts present in small samples. We describe a general method of quantifying
      specific mRNA quickly and easily from purified RNA or directly from a few cells
      by PCR and enzyme-linked immunosorbent assay (ELISA) revelation of the resulting
      products (sensitivity of the last step: < 0.1 fmol). Cells are digested and the
      total cellular RNA is reverse-transcribed and then amplified with 5' and 3'
      primers; the former being 5' biotinylated. The amplification product is captured
      on avidin-coated microplates and quantified by hybridization with a digoxigenin
      labeled internal oligonucleotide probe. After revelation with an anti-digoxigenin
      alkaline phosphatase coupled antibody (anti-DIG-AP1), the amount of hybridized
      probe is determined by optical reading. The results can be easily converted to
      absolute values by comparison with an external DNA standard curve. An internal
      DNA or RNA standard can also be used. The method we describe can be adapted to
      any cellular or viral gene of known sequence in a matter of days. Since it uses
      nonradioactive probes, commercially available reagents and standard microplate
      readers, it is inexpensive and could be automated easily. In this study,
      interleukin-2 mRNA expression could be studied in as few as 40 Jurkat cells. It
      was also possible to quantify human immunodeficiency virus (HIV) DNA from 1500 to
      1.5 copies out of 1.5 x 10(5) human genomic DNA copies.

PMID- 8251177
TI  - Quantification of specific mRNA by flatbed scintillation counting of dual-labeled
      dot blots.
AB  - A dual-labeling technique was developed for direct quantification of specific
      mRNA using a flatbed liquid scintillation counter. This method simultaneously
      measures cpm of 32P- and 35S-labeled probes bound to RNA dot blots and subtracts
      counts due to nonspecific background radioactivity bound to the filter. Probes
      for T-cell receptor and beta-actin (as the internal standard) were hybridized
      both separately and simultaneously to RNA isolated from five different sources.
      There was concordance between the radioactivity measured from single- and dual
      hybridizations for each combination of 35S- and 32P-labeled probes. This
      methodology directly quantifies specific mRNA sequences bound to membranes and
      has potential for measuring gene dosage, without the need for re-probing or
      densitometric analysis.

PMID- 8251178
TI  - 51Cr-release assay adapted to a 96-well format sample reading.
AB  - The application of the Matrix 96, a direct beta counter, to monitor cell-mediated
      lympholysis assays (CML) was investigated. Until now, the gamma rays emitted from
      51Cr, released in the supernatant of the sample following lysis of targets by
      effector cells, were read in gamma counters using individual tubes for each
      sample. The Matrix 96 has been designed to count 96 wells simultaneously for
      assays performed in 96-well microplates. Aliquots of supernatants were spotted on
      a 96-well disposable metal spotting plate and dried prior to reading in the
      Matrix 96. A tight correlation was observed between the counts obtained in the
      Matrix 96 and a gamma counter, which indicates that the detection of electron
      capture beta particles emitted from 51Cr was as accurate as reading gamma rays
      from the same isotope. Both methods confirmed the minimal level of cytotoxicity
      mediated by unstimulated lymphocytes and the high levels of nonspecific cytolytic
      activity mediated by lymphokine-activated killer (LAK) cells against several
      tumor cell lines.

PMID- 8251179
TI  - The maternal-fetal interaction: some controversies and solutions.
AB  - Recent studies have identified some of the mechanisms responsible for protecting
      the mammalian embryo against the potentially hostile immunological maternal
      environment. It is also apparent that these mechanisms vary at different stages
      of reproduction, from fertilisation to implantation and to full development of
      the fetus. They are also unique since they vary from species to species and
      result from exceptional genetic and immunological processes. In this review, a
      few controversial topics have been selected for discussion. They include the role
      of suppressive factors and cells, the transfer of immunocompetent cells across
      the placenta, and claims that habitual recurrent abortion may result from the
      absence of a maternal immune response.

PMID- 8251180
TI  - Immunobiology of the human placental trophoblast.
AB  - Trophoblastic cells use several biological strategies to protect the embryo from
      potential immunological attack by the mother. The most important are the absence
      of major histocompatibility antigens, the presence of unique non-polymorphic HLA
      molecules (HLA-G), and the expression of complement regulatory proteins. The role
      of these factors is analysed in the light of recent studies.

PMID- 8251181
TI  - Immunological infertility in humans.
AB  - This review deals with some of the most controversial problems in the field of
      immunologic infertility and antisperm antibodies (ASA) in humans: (a) sperm
      antigens and their identification; (b) the aetiopathogenesis of the immune
      reaction and the biological effects of ASA; (c) laboratory tests set up for ASA
      detection, and (d) the therapy for immunologic infertility both in vivo and in
      vitro.

PMID- 8251182
TI  - Species diversity in the immunogenetic relationship between mother and fetus: is
      trophoblast insusceptibility to immunological destruction the only essential
      common feature for the maintenance of allogeneic pregnancy?
AB  - Maternal-fetal immune interactions in pregnancy have been examined in a number of
      different species using a wide range of experimental procedures, many of which
      have been incapable of providing information on the specificity of the
      immunological parameters measured. As a result, data have often been
      unconvincing, unsubstantiated or conflicting. It is clear that considerable
      species diversity exists in the precise nature of the maternal immune responses
      elicited against the genetically dissimilar fetus. These may, however, be an
      irrelevant consequence of fetomaternal genetic incompatibilities. A feature
      common to all eutherian mammalian species, that could alone be responsible for
      the maintenance of allogeneic pregnancy, is the apparent insusceptibility of the
      fetal trophoblast to immune destruction. This is effected in some species by an
      absence of appropriate target molecules, particularly classical class I MHC
      antigens, on the trophoblast cell surface, and in others possessing these (and
      possibly other) target structures, by the local trophoblastic secretion of
      soluble factors, not yet fully characterised, that appear to be capable of
      inhibiting binding and interaction with cells of the maternal immune system. As
      there is no convincing evidence for transplacental transfer of significant
      numbers of maternal lymphocytes, the survival of the allogeneic fetus is likely
      to be ensured by the impenetrability of the trophoblastic tissue barrier and its
      resistance to maternal immunologically mediated attack. Should this be firmly
      established, it would not be necessary to invoke any of the immunoregulatory
      mechanisms that have been claimed to be essential for successful implantation and
      development of the mammalian embryo. This would in turn negate the concept of an
      alloimmune aetiology for pregnancy failure and hence also the rationale for those
      therapeutic procedures intended to restore the assumed inadequate maternal
      alloimmune protective responses.

PMID- 8251183
TI  - Maternal and fetal immune responses during pregnancy.
AB  - Pregnancy in the human presents a paradox for the mother's immune system as the
      mechanisms which are essential to protect her from infection have the potential
      to destroy her antigenically foreign fetus. The maternal decidua is comprised
      principally of immune cells and it is into this tissue that the fetal trophoblast
      must invade to establish the placenta. The major factor which appears to prevent
      the rejection of the trophoblast is its expression of HLA-G, a nonpolymorphic
      transplantation antigen. Both local and systemic nonspecific suppressor
      mechanisms have been described which may down-regulate maternal immune responses
      without significantly impairing the ability to fight infections, but there is
      little evidence to suggest that specific blocking factors (antibodies and
      suppressor cells) play an essential role. The placental barrier restricts the
      traffic of cytotoxic cells to the fetus, and cytotoxic antibodies are removed by
      the placenta before they reach the fetal circulation. Thus a combination of
      immune adaptations ensures the success of the pregnancy.

PMID- 8251184
TI  - Mapping of the mouse Rar loci encoding retinoic acid receptors RAR alpha, RAR
      beta and RAR gamma.
AB  - Nuclear retinoic acid receptors RAR alpha, RAR beta and RAR gamma are
      transcription factors that bind all-trans retinoic acid as their ligand and
      mediate its action by activating particular set of genes that contain retinoic
      acid responsive elements in their promoter-enhancers. We have mapped genetic loci
      for these genes using restriction fragment length variants (RFLVs) in
      interspecific backcross mice. None of the Rar loci cosegregated with each other
      or with the new subclass of retinoid receptors, Rxr loci. Rara mapped to mChr 11,
      Rarb mapped to mChr 14, and Rarg mapped to mChr 15. The results are consistent
      with the previous reports and the human data in terms of syntenic homology
      between mouse and human chromosomes.

PMID- 8251185
TI  - Mitosis of rotenone-induced endoreduplication in Chinese hamster cells.
AB  - Endoreduplication was induced by rotenone with an extremely high frequency
      (approximately 90% of all the metaphases) in cultured Chinese hamster cells.
      Endoreduplicated cells were fixed without colchicine or hypotonic treatment, and
      chromosomal configurations were examined in various mitotic stages. The two
      sister chromosomes of each diplochromosome at late prophase were widely separated
      except the centromeric region, but they became gradually paired along the total
      length as the cell cycle progressed to metaphase. The anaphase cells underwent
      multipolar division, resulting in three or four aneuploid daughter cells.
      Indirect immunofluorescence staining using anti-beta tubulin antibody revealed
      tripolar or tetrapolar spindles and unusual equatorial plates.

PMID- 8251186
TI  - Classification and relationships of rice strains with AA genome by identification
      of transposable elements at nine loci.
AB  - We analyzed the presence of p-SINE1 members at five loci in the rice strains
      belonging to seven species with AA genome in the Oryza genus by the methods
      including polymerase chain reaction (PCR). Four p-SINE1 members (p-SINE1-r3, r4,
      r5 and r7) were present at the corresponding loci in all the strains examined.
      One member (p-SINE1-r6) was, however, not present at the corresponding locus in
      most of the African strains of O. glaberrima and O. barthii, but was in the other
      strains. The PCR-amplified fragments containing p-SINE1-r4 in many strains were
      found to be larger due to insertion of either one of two transposable elements,
      named Tnr2 and Ret1, within or near p-SINE1-r4, respectively: Tnr2 is 157 bp in
      length with terminal inverted repeat sequences of about 56 bp; Ret1 is only 13 bp
      in length with a T stretch at its end. Tnr2 was not present in the corresponding
      locus in all the strains belonging to O. sativa Japonica and in some strains of
      O. rufipogon and O. longistaminata, while Ret1 was present only in the two
      strains of O. longistaminata. These results and previous ones obtained from the
      analysis of the other two p-SINE1 members (p-SINE1-r1 and r2) in the Wx gene
      indicate that the elements, such as p-SINE1-r6, Tnr2, Ret1 and p-SINE1-r2, have
      been inserted into the respective loci during divergence of the rice species with
      AA genome. The patterns for the presence and absence of the transposable elements
      at the respective loci enabled us to classify the rice strains with AA genome
      into ten groups and to infer their relationships.

PMID- 8251187
TI  - Genetic polymorphism of prophenoloxidase A1 in Drosophila melanogaster.
AB  - Electrophoretic variations of prophenoloxidase were obtained from natural
      populations of Drosophila melanogaster. A1, one of the 2 isoforms of the
      prophenoloxidases, is polymorphic: 10 fast-migrating and 2 slow-migrating types
      were found in polyacrylamide gel electrophoresis among 271 wild strains. The
      majority were the intermediate-migrating type. By use of these variants, A1 gene
      was mapped at 79.6 on the right arm of the second chromosome. By deletion
      mapping, its cytological position was located at 55A-B. In the electropherograms,
      hybrids between the types differing in mobility exhibited 3 bands, indicating
      that A1 is a dimeric protein. The gene for A1 is expressed through larval, pupal
      and adult stages.

PMID- 8251188
TI  - cDNAs encoding for storage proteins in the tubers of taro (Colocasia esculenta
      Schott).
AB  - Two major protein groups of taro (Colocasia esculenta) tuber were purified, and
      their antisera were used for the screening of the cDNA library constructed from
      poly(A)+ RNA of taro tuber. A cDNA clone obtained by screening with an anti-12 kD
      protein antiserum had an insert 1058 bp-long, and an open reading frame for a
      peptide of 268 amino acids. The analyses of the N-terminal amino acid sequence
      and in vitro translation product suggested that the protein was synthesized as a
      peptide with a molecular weight of 27 kD, and then processed into two mature
      peptides with a molecular weight of 12.5 and 13.9 kD and an extra peptide with a
      molecular weight of 0.6 kD. The cDNA clones obtained using the anti-25 kD protein
      antiserum were highly homologous with each other. One of them had an insert 958
      bp-long and an open reading frame for a peptide with 209 amino acids. The amino
      acid sequence deduced from the nucleotide sequence of this clone indicated that
      the 25 kD proteins were homologous to the trypsin inhibitors of soybean and
      winged bean as well as sporamins, the storage proteins of sweet potato.

PMID- 8251189
TI  - Chiral separation using molecularly imprinted heteroaromatic polymers.
AB  - Novel molecularly imprinted polymer systems utilizing 4-vinylpyridine and 1
      vinylimidazole as functional monomers have been developed for enantioselective
      recognition of carboxylic and N-protected amino acids. Non-covalent interactions
      between the functional monomers and the template molecules were the source of the
      subsequent recognition sites in the resultant polymers. The capacity of the
      polymers for molecular recognition was investigated by using them as stationary
      phases in the HPLC mode. Polymers prepared with 4-vinylpyridine were found to be
      more efficient in racemic resolution than those prepared with 1-vinylimidazole.
      When applying a racemic mixture of the template molecule, the polymers showed
      highest affinity for the enantiomer used as template. Imprints of a racemic
      template molecule, as expected, did not exhibit enantioselectivity. The optimal
      molar ratio of 4-vinylpyridine to the template Cbz-L-Asp-OH in the polymerization
      mixture was determined to be 12:1. In addition to enantioselectivity, the
      investigated polymers demonstrated 'ligand selectivity', e.g., a Cbz-L-Asp-OH
      imprinted polymer was able to separate Cbz-D,L-Asp-OH, but was unable to separate
      Cbz-D,L-Glu-OH.

PMID- 8251190
TI  - Design of novel cationic ligands for the purification of trypsin-like proteases
      by affinity chromatography.
AB  - A number of new cationic ligands have been designed and synthesized for the
      selective resolution and purification of the trypszin-like proteases. A series of
      ligands based on 4-[2'-methyl-4'-(2'',4''-dichloro-1'',3'',5''-triazin-6-ylamino
      ) phenylazo]benzamidine were able to bind to trypsin and the trypsin-like
      proteases, thrombin and urokinase, but bound pancreatic kallikrein only weakly.
      Ligands possessing a second cationic group (either 4-aminophenyltrimethylammonium
      or 4-aminobenzamidine) substituted onto the triazine ring displayed higher
      affinities than the parent compound for trypsin in solution but bound the enzyme
      weakly or not at all after immobilization. In contrast, these bis-cationic
      ligands bound pancreatic kallikrein in solution and following immobilization. The
      presence of the second cationic group was crucial, since its replacement by
      neutral or anionic groups led to loss of affinity for pancreatic kallikrein. One
      of the bis-cationic ligands was used to purify pancreatic kallikrein 9.5-fold
      from a crude pancreatic extract in 79% yield, to generate a product 99.9% free of
      contaminating trypsin activity.

PMID- 8251191
TI  - Using a neural network to identify potential HLA-DR1 binding sites within
      proteins.
AB  - The presentation by antigen-presenting cells of immunodominant peptide segments
      in association with major histocompatibility complex (MHC) encoded proteins is
      fundamental to the efficacy of a specific immune response. One approach used to
      identify immunodominant segments within proteins has involved the development of
      predictive algorithms which utilize amino acid sequence data to identify
      structural characteristics or motifs associated with in vivo antigenicity. The
      parallel-computing technique termed 'neural networking' has recently been shown
      to be remarkably efficient at addressing the problem of pattern recognition and
      can be applied to predict protein secondary structure attributes directly from
      amino acid sequence data. In order to examine the potential of a neural network
      to generalize peptide structural features related to binding within class II MHC
      encoded proteins, we have trained a neural network to determine whether or not
      any given amino acid of a protein is part of a peptide segment capable of binding
      to HLA-DR1. We report that a neural network trained on a data base consisting of
      peptide segments known to bind to HLA-DR1 is able to generalize features relating
      to HLA-DR1-binding capacity (r = 0.17 and p = 0.0001).

PMID- 8251192
TI  - [The construction of human genome YAC library and screening by hybridization of
      membrane high density spotted in array].
AB  - The human genomic YAC (Yeast Artificial Chromosome) library was constructed with
      human white blood cell and the cell line GM1 414 containing 4 X chromosome DNA
      using pYAC 4 as vector. Twenty thousand YAC clones were obtained with insert size
      of 400-1000kb. A set of YACs containing entire DMD geneDNA sequence were
      selected.

PMID- 8251193
TI  - [Comparative observation on several indices of nuclear damage induced by MMC in
      rat peripheral lymphocytes at G0 phase].
AB  - In this study the rat peripheral lymphocytes were treated with various doses of
      MMC, lymphocytes blood smear was prepared after 18h and was observed. The results
      showed that the nuclear damage of lymphocytes at Go phase was induced by MMC, and
      dose-dependent relationship was revealed for FMN (frequency of micronucleus), FIN
      (frequency of irregular nucleus) and FKN (frequency of karyorrhetic nucleus).
      Compared with the traditional micronucleus test, rat peripheral lymphocytes
      nuclear anomaly test seemed to be more sensitive and reasonable. It could
      therefore be considered as a short-term mutagentic test for preliminary screening
      and it was worthy of more study.

PMID- 8251194
TI  - [Unequal genetic contributions of parents to offsprings and their optimal
      control].
AB  - Due to the joint effects of natural and artificial selection, the proportions of
      genetic materials originating from different parents may vary in the gene pool of
      offsprings, and this creates a problem of unequal genetic contributions of
      parents to offsprings. It is shown that unequal genetic contribution
      substantially affects the genetic gain via realized selection differential and
      effective population size, and brings error to the empirical prediction formulae
      of selection response: R = i.sigma P.h2. The aim of breeding should be to select
      the genetically superior individuals and then to make more genetic contributions
      of better parents to offspring gene pool. However, the latter aspect has been
      ignored in theoretical study as well as in certain breeding practice. To deal
      with the problem, a method which takes maximizing genetic advance as general
      objective and considers some breeding restrictions, is suggested to control the
      percentage of genetic contributions. A numerical example from egg-type chicken
      breeding is used to demonstrate the effects of optimal control of unequal genetic
      contributions. The result indicates that at the same level of effective
      population size, the realized selection response for different traits under the
      optimal pattern of unequal genetic contributions could be 34.27-216.57% higher
      than that under the actual unequal pattern.

PMID- 8251195
TI  - [Cloning and sequencing of attacus ricini nuclear polyhedrosis virus polyhedrin
      gene].
AB  - Attacus ricini is a species of insect which only grows in China. It is expected
      to construct a new expression system for genetic engineering by using ArNPV as a
      vector. We have established an ArNPV gene library. The 1.1 kb DNA fragment
      containing ArNPV Ph gene was subcloned. Sequencing analysis shows that the 735 bp
      Ph structural gene has the homology of 76% and 81% with those of AcNPV and BmNPV
      respectively. The Rohrmann box in the ArNPV 5'-end regulation region is very
      similar to those of various other NPVs, but the 3'-end downstream sequence has
      almost no homology with those of AcNPV and BmNPV, demonstrating the
      characteristic property of the structure of ArNPV Ph gene. Other structural
      features of the Ph gene promoter are also discussed in this paper.

PMID- 8251196
TI  - [Effect of ribosomal protein mutation on the expression of alkaline protease gene
      in Bacillus subtilis].
AB  - Altogether 19 strains belong to 13 species of ribosomal protein mutants of
      Bacillus subtilis were tested in vitro transcription--translation system for
      their influence on the translation of alkaline protease gene (apr). It was found
      that 10 species (13 strains) of ribosomal protein mutants did affect the
      translation of apr mRNA. Streptomycin-dependent (Str-D) ribosomes almost did not
      translate the apr mRNA. Str-D inhibited the expression of apr gene at the
      translational level, but had no influence on neutral protease gene. There is a
      secondary structure complex at the translation initiation region of apr mRNA.
      When one of the secondary structure was destroyed by site directed mutagenesis,
      the translation efficiency was enhanced by 7.3 to 9.1 folds. The higher order
      structure of Str-D and Str-R ribosome were different and so were the affinity of
      Str-D and Str-R 30S subunits to the 5' end of apr mRNA. These results suggest
      that Str-D ribosomes could not translate apr mRNA because of the secondary
      structure complex, low initiation strength of apr mRNA, and alteration of the
      higher order structure of the Str-D ribosomes.

PMID- 8251197
TI  - [Cloning of beta-amylase gene from B. substitute and its expression in E. coli].
AB  - The gene coding for beta-amylase with raw starch-digestion ability was isolated
      from B. substitute R2 which was selected in this lab. The procedure used in this
      screening was developed in this work by the method named nutrition-restriction.
      The DNA fragment containing the beta-amylase gene was 5.25 kb in length. There
      was no difference in enzymological properties between the beta-amylase produced
      by the gene-donor strain and the expression product of E. coli. The yield of the
      cloned beta-amylase was over 500 IU/ml in our laboratory culture condition, the
      RDA value was 57%, and all of this enzyme were found to be secreted into medium.

PMID- 8251198
TI  - [Cloning and sequence analysis of salmon growth hormone cDNA].

PMID- 8251199
TI  - The reverse experiment in two-stage skin carcinogenesis. It cannot be genuinely
      performed, but when approximated, it is not innocuous.
AB  - One of the main assumptions of the two-stage theory of skin carcinogenesis is
      that the reverse experiment (promotion before initiation) is innocuous and that
      this in itself proves that there is a qualitative difference between the
      biological effects of initiators and promoters. However, almost all previous
      experiments in two-stage carcinogenesis have been arranged to justify the theory.
      Therefore, in order to test the theory scientifically, a series of experiments
      was set up comparing the tumor crop in classical two-stage and in reverse
      experiments. In most, a small, single dose of DMBA (200 or 100 nmol) was applied
      topically before or after a long-term course of 17 or 10 nmol TPA, but in one
      series, DMBA in larger doses (4,000 or 8,000 nmol) was given intraperitoneally.
      In another experiment two topical applications of 17 nmol TPA were given before
      or after a long-term course of very small doses (10 nmol) of DMBA applied twice a
      week. DMBA and TPA were generally applied in acetone. The results were
      statistically analyzed either from the start of the experiment, or from the time
      of DMBA application. A total of 736 mice were used, and they were studied once a
      week for papilloma and carcinoma development. No difference between classical and
      reverse experiments could be found as regards the carcinoma crops. For
      tumorigenesis (mostly papillomas) it was generally found that the reverse
      experiment was not innocuous, but produced a larger tumor crop than that produced
      by either DMBA or TPA alone. The two substances showed a reciprocal enhancing
      effect, which was sometimes weak, sometimes additive, and sometimes even
      synergistic, and was statistically most significant when the results were
      assessed from the time of DMBA application. Although the reverse experiment was
      not in any way innocuous it always resulted in a lower tumor crop than the
      classical sequence of DMBA followed by a course of TPA treatment. However, the
      lower tumor crop in the reverse experiment cannot be used to prove a qualitative
      difference between initiators and promoters. A course of TPA treatment alters the
      skin considerably, producing epidermal hyperplasia, an increased rate of cell
      proliferation, chronic inflammation and many other changes. A topical application
      of DMBA to such an altered skin is likely to have a considerably reduced
      tumorigenic effect. A 20-week resting period after TPA treatment seems to
      increase the effect of a final DMBA application, probably because part of the
      induced resistance is removed again.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8251200
TI  - Studies of the immunological effects of interleukin-2 in patients with bladder
      cancer and renal cell carcinoma.

PMID- 8251201
TI  - Public health and paradigms.

PMID- 8251202
TI  - Child accident data: accessible and available?
AB  - The accessibility, availability and content of health service data on accidental
      injuries occurring in childhood was investigated. Death data, admission data and
      Accident and Emergency (A&E) data were examined. Considerable problems were
      experienced with the availability of routine data, and the available information
      was found to be limited by the nature and content of the data collected by
      computerized systems. Data were limited both in terms of providing information to
      the local Accident Prevention Working Group and for the monitoring of preventive
      activity. It was also determined that none of the data were being audited. It was
      concluded that there is a need for national agreement concerning both cause of
      injury coding and severity coding.

PMID- 8251203
TI  - The provision and use of medical services during the 1991 World Student Games in
      Sheffield.
AB  - This paper describes the provision and use of medical services organized by
      Sheffield during the World Student Games in 1991. A descriptive study of medical
      and physio-therapy records, together with minor incident logs and hospital
      referrals, was carried out. It was found that 571 medical records and 357
      physiotherapy records were completed, of which 83 per cent were generated at the
      Games Village. The majority of patients were competitors, although team officials
      accounted for a disproportionate number. Most physiotherapy requests were for
      sports injuries, whereas this was not so for medical cases. Twenty-five per cent
      of medical records and 40 per cent of physiotherapy records were for recurrent
      conditions which had started before arrival. Athletics and football accounted for
      the greatest number of records per competitor. During the Games, 82 patients were
      referred to hospital, of whom only 12 were admitted. The largest group of
      hospital referrals was for dental treatment, and the next largest was for minor
      trauma. A total of 1089 minor incidents were recorded, mainly at the competition
      venues and in the Physiotherapy Room at the Games Village. In addition, the Red
      Cross and the St John Ambulance Association attended to 330 people during the
      Games. The smallest national teams tended to make most demands on services,
      probably because the larger teams were accompanied by their own medical and
      physiotherapy staff. It is concluded that the main demands for medical services
      at the World Student Games were for general practice and physiotherapy at the
      Games Village, and for first aid at competition venues.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8251204
TI  - The patient profile approach to assessing the cost of AIDS and HIV infection.
AB  - Despite interest in the costs associated with HIV infection, little useful
      information exists to aid those planning patient care. The results of costing
      studies, which are mainly North American, are difficult to apply to the National
      Health Service. Moreover, they have generally ignored HIV infection before formal
      diagnosis of AIDS. A patient profile approach was devised to supply data on the
      type, amount and cost of services supplied to patients in the Northern region.
      This method produces longitudinal treatment and cost profiles, and provides a
      temporal perspective, which is essential given the speed at which care has
      changed to date. This method also allows identification of a wide array of
      services, costs and social factors. This paper describes a pilot study to develop
      and test these methods. The sample of 24 randomly selected patients constituted a
      heterogeneous group; the individuals affected, the type and number of services
      supplied and costs all varied widely. A typical patient could not be described.
      Our results illustrate the powerful analyses which this approach permits. Further
      application will allow improved evaluation of the overall costs and the effects
      of different patterns of care.

PMID- 8251205
TI  - Today or in the past? The origins of ischaemic heart disease.
AB  - Recent studies have suggested that regional differences in death rates from
      ischaemic heart disease (IHD) may result from exposure to poverty in foetal and
      early infant life. The suggestion is that such influences 'permanently set
      structures and metabolic processes, so-called programming'. On this theory,
      current falls in IHD death rates reflect much earlier reductions in poverty. If
      the theory were correct, the fall in rates would begin with younger age groups
      and be reinforced only at the pace at which each new birth cohort reached adult
      life. There is no evidence of such a cohort effect. Rates fell simultaneously
      over a very brief period in each country and region examined. The results are
      more compatible with theories involving contemporary lifestyle changes.

PMID- 8251206
TI  - Multiple hospital admissions in a calendar year.
AB  - Hospital in-patient workload is routinely measured as episodes of care. We report
      on the extent to which counts of episodes of care differ from counts of patients
      treated in different specialties and in different age groups. Linked records of
      hospital care in a population of 1.9 million people, collected over an 11-year
      period (1976-1986), were analysed. The all-ages multiple admission ratio (the
      number of admissions per 100 people admitted in the same specialty and year)
      varied between specialties from 102 to 171. Medical specialties tended to have
      higher ratios than surgical ones. The influence of age on multiple admission
      ratios varied between specialties, although in general the ratios increased with
      increasing age. There were progressive but small increases in multiple admission
      ratios over the period studied in a number of specialties but, by and large,
      stability over time was more striking than any change. The information presented
      could be used to estimate person-based admission rates from available episode
      based data where the former are not available. This should be helpful both in
      managing hospital resources and in purchasing care on behalf of resident
      populations. Purchasers in particular should be aware of numbers of people being
      treated as well as the numbers of episodes of care provided.

PMID- 8251207
TI  - Audit of public health medicine: the northern region's approach.
AB  - Public health doctors are required to audit their work, a principle endorsed by
      the Faculty of Public Health Medicine. Although general concepts of audit in
      clinical medicine are likely to apply to public health medicine, the practical
      problems are likely to be different. Public health medicine, therefore, needs to
      experiment with approaches to audit until general principles are established. The
      implementation of public health medicine audit in the Northern Region is reviewed
      here, highlighting the establishment of structures (e.g. a public health medicine
      audit promotion group and audit link-persons), processes (e.g. study days,
      exchange of information) and outcomes (e.g. audits undertaken and standards
      devised). The foundations for audit of public health medicine have been built
      upon wide debate and consultation, locally written documents detailing the
      arguments and making practical suggestions for change, ownership of policy-making
      decisions by a regional forum of public health doctors, day-to-day responsibility
      resting in an audit group, a heavy emphasis on communication including the
      gauging of opinions, attitudes and behaviour by survey, a perception that public
      health medicine has the same rights and obligations towards audit as other
      medical specialties, and the view that audit in our specialty will require time
      and patience to implement. The challenge remains of ensuring the implementation
      of cost-effective audit in the routine practice of public health medicine.

PMID- 8251208
TI  - More and better services for people with learning disabilities.
AB  - A prevalence study of disability, use of and need for services was undertaken to
      estimate the need for NHS and other forms of residential, day and respite care
      for people with severe learning disabilities. Subjects aged 20 or more were drawn
      from the Leicestershire Learning Disabilities Register (n = 1887). Information
      was collected by interview with a professional career. The age-specific
      prevalence was 2.9 per 1000 and the response rate was 88 per cent. A disability
      rating predicted consultant opinion on need for NHS residential care with a
      sensitivity and specificity of 82 per cent. Predictive disability factors
      included problems with behaviour, toileting, speech, epilepsy, postural deformity
      and use of a wheelchair. Planning targets per 100,000 population aged 20 or more
      were estimated as follows: NHS residential care--47 places; other residential
      care--103 places; respite care--36 people; day care--224 places. The need for
      residential care and medical support remains eminently predictable within the new
      philosophical framework of provision. Since 1971 the need for NHS residential
      places has decreased but remains important for people with high dependence. Day
      care targets have increased and diversified.

PMID- 8251209
TI  - Use of Coroner's reports for surveillance of accidental death.
AB  - The objective of this study was to investigate the possibility of using Coroner's
      reports on accidental deaths as the basis of a surveillance system. The Coroner's
      reports of childhood accidental deaths in Northern Ireland over a five-year
      period (224 deaths) were reviewed. Outcome measures included the delay between
      time of death and registration of death and the usefulness of the report in
      assessing the preventability of the accident. The timing of Coroner's reports
      could facilitate monitoring of trends for particular categories of accident and
      allow information in the reports to be used as a basis for preventive programmes.
      At present, however, the reports which the Coroner uses to inform the Registrar
      General of his or her findings are not of a standard format, and in many cases do
      not report enough detail to allow an analysis of the circumstances of the
      accidents which could be used to establish opportunities for prevention.

PMID- 8251210
TI  - Which maternity unit? Who makes the choice?
AB  - To investigate the factors determining the choice of maternity unit in an outer
      London district where half of all births occur outside the district, a self
      administered questionnaire was distributed by community midwives at postnatal
      home visits. The main outcome measures were: (1) proportion of mothers able to
      deliver in unit of first choice; (2) proportion of mothers making a personal
      choice rather than taking advice from their GP; (3) reasons for not choosing
      district unit, by parity. It was found that 28/166 (17 per cent) of mothers were
      unable to deliver in their first choice of unit, and 3/166 (2 per cent) were
      unable to obtain their second choice. Of the women who did obtain their first
      choice, 84/136 (62 per cent) had made a personal decision rather than being
      advised or told by their GP; 58 of these 84 personal deciders went outside the
      district, but for 36/58 (62 per cent) this was either because the other unit was
      nearer their home or because they had delivered there before. It is concluded
      that, although GPs are theoretically free to refer to any maternity unit, a
      sizeable minority of women are unable to realize their own choices. GPs seem to
      regulate flows by advising women without strong personal views to attend the
      local unit. Differences in the quality of care as perceived either by women or
      their GPs do not seem particularly important in determining choices. The
      introduction of an internal market in maternity care seems unlikely to result in
      improved quality of care.

PMID- 8251211
TI  - Quarterly Communicable Disease Review January to March 1993. From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 8251213
TI  - Doctors' understanding of public health medicine.

PMID- 8251212
TI  - Cost-benefit analysis of the introduction of mass vaccination against hepatitis B
      in Italy.

PMID- 8251214
TI  - Mining communities and health risks.

PMID- 8251215
TI  - Estimated date of delivery from last menstrual period and ultrasound scan: which
      is more accurate?
AB  - The aim of this study was to determine which is the more accurate predictor of
      the date of delivery for pregnant women in a community-based population: a
      calculation based on the last menstrual period or a prediction based on the
      measurement by ultrasound scanning of well-recognized fetal characteristics. A
      prospective study was conducted of 225 consecutive women reporting their
      pregnancy in a semi-rural general practice; 106 women were included in the
      analysis. The results showed that in over 50% of cases the estimated date of
      delivery derived from the ultrasound scan was more accurate than that derived
      from the last menstrual period, whatever the discrepancy between the two
      predictions. It can be concluded that all professionals involved with antenatal
      care should ignore the estimated date of delivery derived from the last menstrual
      period once a satisfactory scan has been obtained.

PMID- 8251216
TI  - Why do general practitioners recognize major depression in one woman patient yet
      miss it in another?
AB  - The aim of this study was to establish whether psychiatric patient
      characteristics and the presence of physical illness affected general
      practitioners' recognition of major depressive illness in women patients. The 30
      item general health questionnaire was used as a first stage screening instrument
      for psychiatric morbidity and each patient selected was interviewed, usually
      within three days of consulting their general practitioner, using the combined
      clinical interview. A sample of 72 women with major depressive disorder was
      obtained from patients consulting 36 general practitioners mainly from the south
      west Thames region of England, each general practitioner providing one patient he
      or she had correctly recognized as being depressed and one patient whose
      depression had not been recognized. Few differences were found between the groups
      with recognized and unrecognized depression in their psychiatric or physical
      features. More patients with unrecognized depression experienced physical illness
      and were tired. Patients with serious physical disease were five times more
      likely not to be recognized as depressed than those without physical disease.
      Patients with recognized depression described a more distinct quality to their
      depressed mood. Women with unrecognized major depression are similar to those
      women whose major depression is recognized by their general practitioner. These
      findings require further elaboration by process and content analysis of the
      women's consultations.

PMID- 8251217
TI  - Access to general practice and general practitioners by telephone: the patient's
      view.
AB  - Postal surveys were conducted among samples of patients in four practices to
      determine accessibility of surgeries and general practitioners by telephone. Over
      half of the respondents reported being unable to get through to the surgery on
      their first attempt. Significant differences between practices were related to
      the number of patients served by each incoming line. Although all of the general
      practitioners involved were accessible to patients by telephone, only half of the
      respondents knew this. Significant differences in awareness levels between
      practices were related to policies and methods of disseminating this information.
      Satisfaction with the help received from doctors by telephone was uniformly high,
      but patients were less satisfied with the process of contacting a doctor,
      particularly where receptionists questioned callers about their problem. It is
      suggested that practices review the adequacy of their telephone systems against a
      recommended standard of one incoming line per 2500 patients and consider how
      information about their telephone policies and services can be effectively
      communicated to patients. Reception staff may need additional guidance on
      managing telephone contacts with patients.

PMID- 8251218
TI  - Why do patients change their general practitioner? A postal questionnaire study
      of patients in Avon.
AB  - The aim of this confidential postal questionnaire study was to determine why
      patients change their general practitioner. Among 1423 patients who changed their
      general practitioner without changing their address the reason most commonly
      given for leaving a general practitioner was distance (41%)--three quarters of
      these patients mentioned only distance. Just over one third of respondents (35%)
      mentioned dissatisfaction with the personal care given by the general
      practitioner and 36% mentioned dissatisfaction with practice organization.
      Specific patient requirements, such as a woman doctor, were not commonly
      mentioned. Convenience was the commonest reason given for choosing a new doctor
      (53%), with recommendation or reputation mentioned by 36% of respondents and
      positive expectations of service by 37%. The proportion of patients that changed
      from any one practice was small. This type of survey may prove a useful method
      for family health services authorities to identify practices with a higher than
      normal level of patient dissatisfaction.

PMID- 8251219
TI  - Tendency to being bitten by insects among patients with eczema and with other
      dermatoses.
AB  - In order to ascertain whether patients with eczema are more prone to being bitten
      by insects than those with other dermatoses, data were collected by interview and
      questionnaire from 496 patients attending the outpatient department of a hospital
      in Sydney and a general dermatological practice in Geelong, Australia. Of the 93
      patients with eczema 65% claimed they were prone to insect bite and that they
      were bitten in preference to other people when in a group, compared with 17% of
      the 403 patients with other chronic dermatoses. Similar proportions of both
      groups (approximately 50%) had used insect repellents. Excluding those with
      eczema 30% of the 149 patients with a family history of atopy claimed they were
      prone to being bitten by insects compared with 8% of the 254 patients without a
      family history of atopy. There was no difference in the prevalence of eczema or
      family history of atopy between men and women, but more women felt themselves to
      be susceptible to insect bites than men. There is evidence that patients with
      eczema and those with a family history of atopy are prone to being bitten by
      insects. Further confirmatory work, perhaps using volunteers and mosquitoes, is
      indicated. However, patients with severe eczema or a family history of atopy
      should take care when travelling to areas where disease-carrying insects are
      prevalent.

PMID- 8251220
TI  - Partners or partisans? Patient participation at Marylebone Health Centre.
AB  - This paper outlines some of the issues which arose for patients and professionals
      involved in patient participation projects at the Marylebone health centre in
      London. It describes the projects undertaken and focuses on the practical
      implications of working with rather than for patients. Dilemmas surrounding
      patient participation are discussed, including the ways volunteers are rewarded,
      how doctors and patients can share knowledge, how participation is affected by
      professional boundaries, and why a regular group meeting may not necessarily be
      the best way to involve patients in decision making. The successes of patient
      participation are also highlighted.

PMID- 8251221
TI  - Salaried general practice in Czechoslovakia: personal observations and
      impressions.
AB  - In 1991, a visit was undertaken, to the former Czechoslovakia, during which
      discussions were held with general practitioners. Some personal observations and
      impressions from the visit are presented. For four decades, salaried general
      practice was a feature of the Czechoslovakian health care system. Primary health
      care comprised three strands: paediatric services, an occupational health service
      and community general practitioner care. The main point of service delivery was
      the polyclinic which, although being large and impersonal, provided easy access
      to other primary and secondary services. General practitioners, over half of whom
      were women, had regular leave entitlement and predictable hours of work, out of
      hours work being provided through separate contracts based on primary care
      emergency centres. However, doctors were poorly paid compared with industrial
      workers. Following the 'velvet revolution' in 1989, all aspects of the health
      service have been subject to major review, and salaried general practice is
      likely to give way to a more entrepreneurial system.

PMID- 8251222
TI  - Study of teenage care in one general practice.

PMID- 8251223
TI  - Hospital anxiety depression scale.

PMID- 8251224
TI  - Role of neuromuscular excitability in metabolic problems.

PMID- 8251225
TI  - Cholesterol level testing.

PMID- 8251226
TI  - Recording ethnic origin.

PMID- 8251227
TI  - Automated external defibrillation.

PMID- 8251228
TI  - Family planning services.

PMID- 8251229
TI  - Potential pitfalls of minor surgery in general practice.

PMID- 8251230
TI  - Making changes? Audit and research in general practice.

PMID- 8251231
TI  - Incidence of episodes of acute asthma and acute bronchitis in general practice
      1976-87.
AB  - The incidence of episodes of acute asthma and acute bronchitis was analysed for
      an 11-year period and studied in relation to epidemiological data on viral
      illness and virus isolation data. Between 1976 and 1987, the weekly returns
      service estimates of the incidence of acute asthmatic episodes in England and
      Wales increased from 10.2 to 27.1 per 100,000 patients per week (all ages). The
      increase was most marked in children up to the age of 14 years. Acute bronchitis
      attack rates (all ages) increased from 78.7 to 111.9 per 100,000 patients over
      the same period. Because of this rise in rates of acute bronchitis, it is
      unlikely that labelling shifts contributed to the increase in reported episodes
      of asthma. These data support the belief that the rise in the prevalence of
      asthma is real, and also that in the United Kingdom this rise may even be
      underestimated by partial concealment in the rates of acute bronchitis. In 1987,
      if 10% of attacks of acute bronchitis were attacks of asthma, this would
      represent a 41% underestimation of asthma attack rates. Rates for other
      respiratory illnesses showed a fall over the same period, apart from the common
      cold which showed an increase. The winter increase in acute bronchitis coincided
      with viruses with strong seasonal patterns (respiratory syncytial virus,
      parainfluenza viruses 1 and 2 and influenza A and B), but there was no evidence
      that these viruses were related to the overall increase in acute asthma attacks
      over this 11 year period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251232
TI  - Hormone replacement therapy: a study of women's knowledge and attitudes.
AB  - Hormone replacement therapy can successfully treat menopausal symptoms. A postal
      questionnaire was used to investigate the knowledge of and attitudes to hormone
      replacement therapy of an age-stratified, computer-generated, representative
      sample of 1500 women living in the Grampian region of Scotland. A response rate
      of 78% was achieved. Comparisons were made between women of differing age,
      educational background and their current or past experience of hormone
      replacement therapy. The questionnaire also assessed their knowledge of
      osteoporosis, including the possible beneficial role of hormone replacement
      therapy. The results showed that women had a poor knowledge of the potential
      risks and benefits of oestrogen, lack of knowledge being greatest in the less
      educated and older women. The majority of women agreed with the view that because
      the menopause is brought on by diminished hormone levels, it should be viewed as
      a medical condition and treated as such, and also that a woman who experiences
      distressing menopausal symptoms should take hormone replacement therapy. Despite
      this, relatively few postmenopausal women were currently taking hormone
      replacement therapy (9%) or had taken the treatment in the past (7%), although
      many had experienced menopausal symptoms for over six months. The most common
      reason for postmenopausal women never having taken hormone replacement therapy
      was that they had never considered the treatment (70%) and had not discussed it
      with a doctor (79%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251233
TI  - Assessment of elderly people in general practice. 4. Depression, functional
      ability and contact with services.
AB  - The aim of this study was to look at the interrelationship between depression,
      physical disability and contact with services. In a random sample of 239 people
      aged 75 years and over from nine general practices in north London, depression
      (as measured by a shortened version of the comprehensive assessment and referral
      evaluation schedule) was found to be significantly associated with being a woman,
      and inability to perform a number of activities of daily living. Consumption of
      three or more prescribed medicines, a home visit by the general practitioner in
      the previous three months and contact with health visitors and home helps were
      all significantly more likely among depressed patients. There were also
      significant associations between loss of functional abilities, measured using
      items from an activities of daily living scale, and use of certain services:
      general practitioner home visits and reduced mobility indoors and both home help
      and district nurse visits to those with difficulty in bathing. Multiple logistic
      regression analysis suggested that contact with services was principally
      associated with loss of mobility, although contact with home helps was
      independently associated with depression, when adjustment was made for functional
      impairment.

PMID- 8251234
TI  - Comparison of risk factors for coronary heart disease among attenders and non
      attenders at a screening programme.
AB  - Few objective comparative data are available from primary care on the prevalence
      of risk factors for coronary heart disease among those who do and do not attend
      screening programmes. This study set out to examine differences in risk factors
      between attenders and non-attenders at such a coronary heart disease screening
      programme. The 2402 patients in the age range 25-55 years who attended the
      original health check were examined by a practice nurse, and a questionnaire
      about health issues was completed. A one in 10 systematic sample of the 1398
      patients who did not attend the original screening programme were approached and
      after considerable effort 98 were persuaded to attend for the same examination
      and questionnaire analysis. The 98 non-attenders were found to be older and to
      have a higher mean body mass index, mean cholesterol level, mean systolic blood
      pressure and mean diastolic blood pressure than the 2402 attenders. The non
      attenders were more likely to be in the lower social classes, to have a personal
      or family history of coronary heart disease and to smoke than attenders. They
      were less likely to be highly educated and to have an unacceptably high level of
      alcohol consumption. The results of this study suggest that clinics that invite
      patients to attend are likely to attract those with lower risk factor profiles.
      For coronary heart disease prevention to be effective there is a need to cater
      for patients opportunistically.

PMID- 8251235
TI  - Comparison of the health and lifestyle of general practitioners and teachers.
AB  - A total of 704 general practitioners and 588 teachers responded to a
      questionnaire about their health and lifestyle in 1991 (response rates 82% and
      87%, respectively). The results for lifestyle measures were compared with those
      of a similar questionnaire completed by about half of each group two years before
      -there were no changes in the answers of either occupational group in the
      intervening two years. In 1991, 9% of general practitioners and 15% of teachers
      drank 22 units of alcohol per week or more; 13% of general practitioners and 23%
      of teachers reported troublesome depression and 31% of doctors and 37% of
      teachers excessive anxiety in the preceding 12 months. Teachers had more sickness
      absence, and significantly more experienced a need for daily alcohol and binge
      eating, and reported sleep difficulties, depression and anxiety than general
      practitioners. Self-medication among general practitioners was common and overall
      accounted for 83% of the medication taken by doctors. A follow-up survey of non
      respondents found that only 11% of general practitioners and 11% of teachers
      indicated they had a health problem they wished to conceal or that they felt the
      questions were too intimate. General practitioners' lifestyle habits are better
      than those of teachers and published figures for the general population. The
      frequency of reported mental health problems in both professions gives cause for
      concern.

PMID- 8251236
TI  - Audit of a system for dealing with a practice's laboratory test results.
AB  - In order to improve efficiency in a non-computerized practice of 4700 patients
      the system for dealing with laboratory test results and communicating them to
      patients was audited over a two-week period. The audit involved a questionnaire
      for the practice team, a postal questionnaire to 36 patients, and an analysis of
      doctors' and receptionists' workload when dealing with laboratory test results. A
      new system was introduced, with two receptionists logging investigation details
      into a newly designed results book, and with date/process stamping of results.
      The new system was re-audited using another practice questionnaire and analysis
      of doctors' and receptionists' workload and found to be as effective as the old
      system but less time consuming, largely owing to the layout of the new results
      book. All members of the practice team were more satisfied with the new system.
      The function of a results book and its role in doctor-patient communication is
      discussed.

PMID- 8251237
TI  - Effectiveness of general practice interventions for patients with harmful alcohol
      consumption.
AB  - Harmful alcohol consumption can have severe consequences for both the individual
      and society. A review of the six published studies on the effectiveness of
      general practitioner interventions for individuals with harmful alcohol
      consumption suggests that between five and 10 minutes of advice leads to
      reductions of alcohol consumption of around 25-35% at follow up six months or one
      year later. Two of the three studies which failed to demonstrate an intervention
      effect had inadequate sample sizes and in two of the studies the control group
      was a comparison group which received minimal advice to reduce alcohol
      consumption. There was greater evidence for an intervention effect among men than
      women. The methodological problems of the studies are discussed.

PMID- 8251238
TI  - Monitoring the standard of deputizing services.
AB  - The standard of medical care provided by deputizing services is important for
      patients receiving care and for doctors using the service. The monitoring of
      these standards is discussed here in terms of what should be measured, how this
      should be done, and who should carry out this monitoring. The features to be
      taken into account include professional values, accessibility, clinical
      competence, and ability to communicate. Various bodies, such as the deputizing
      services, family health services authorities, and individual doctors and patients
      will usefully be involved in assessing standards. The future might hold radical
      solutions to the management of out-of-hours calls. These solutions could involve
      patients, general practitioners and the deputizing services. The result must be
      that patients receive the best possible care.

PMID- 8251239
TI  - Anticoagulant therapy.

PMID- 8251240
TI  - Anticoagulant therapy.

PMID- 8251241
TI  - Anticoagulant therapy.

PMID- 8251242
TI  - Accidents among children.

PMID- 8251243
TI  - Advance directives.

PMID- 8251244
TI  - Assessing elderly people.

PMID- 8251245
TI  - An open-access dental practice.
AB  - The DoH funded a drop-in dental practice in inner-city Salford for 12 months. Its
      aim was to increase accessibility and availability of dental services to people
      not registered with a dentist. It operated on a no-appointment basis and priority
      was given to those in pain and/or on their initial visit.

PMID- 8251246
TI  - 'The use of a caries detector dye during cavity preparation'.

PMID- 8251247
TI  - 'Dental amalgam: a review'.

PMID- 8251248
TI  - A longitudinal study of the clinical performance of porcelain veneers.
AB  - A total of 315 porcelain labial veneers were fitted in 96 patients in two
      teaching hospitals, between July 1986 and October 1991, and were evaluated after
      a period of up to 63 months. During the evaluation period 53 (17%) restorations
      in 31 (32%) patients presented with a problem at review. Of these, 25 (8%) were
      of a minor nature and the veneer remained in use while 34 (11%) debonded or were
      removed. Increased problem and failure rates were associated with veneers placed
      on existing restorations, where tooth surface loss had occurred prior to
      treatment, and where inappropriate luting agents were employed. Age, gender,
      fabrication technique (platinum foil or refractory die), use of rubber dam and
      year of bonding were not significant factors.

PMID- 8251249
TI  - A six-month clinical study of the effect of a pre-brush rinse on plaque removal
      and gingivitis.
AB  - The effect of a pre-brush rinse (Colgate Plax, Colgate UK) containing 0.03%
      triclosan (Irgacare MP, Ciba-Geigy Corp.) and 0.125% of a copolymer of
      methoxyethylene and maleic acid (Gantrez, ISP Corp.) on existing plaque and
      gingivitis over a 6-month period was compared to a matching placebo pre-brush
      rinse. The study was a double-blind, parallel design utilising 125 subjects, 117
      of whom completed the 6-month period. Subjects rinsed twice daily for 60 seconds
      with 15 ml of their assigned pre-brush rinse. Immediately after rinsing, subjects
      brushed their teeth for 30 seconds with a fluoride dentifrice and a soft-bristled
      toothbrush. After 3 and 6 months, the levels of plaque and gingivitis were
      significantly lower in the triclosan/copolymer rinse group when compared with the
      placebo rinse group. The beneficial effects of the active rinse were particularly
      evident on the surfaces of teeth which are poorly cleaned by mechanical
      procedures. No side effects, such as staining, were observed or reported. The
      results indicate that the twice daily use of a pre-brush rinse containing
      triclosan and copolymer can provide significant adjunctive benefits to mechanical
      oral hygiene procedures.

PMID- 8251250
TI  - 'Strawberry gums'--a case of Wegener's granulomatosis.
AB  - We report a case of Wegener's granulomatosis (WG), localised to the upper
      aerodigestive tract, which presented as an unusual form of hyperplastic
      gingivitis in a 36-year-old female. The clinical, serological and
      histopathological findings are described. The resemblance of the affected gums to
      over-ripe strawberries is emphasised, in order to draw attention to this
      characteristic oral manifestation of a rare and potentially life-threatening
      condition. The response to co-trimoxazole as sole therapy is noted.

PMID- 8251251
TI  - Mandibular infected buccal cyst or a paradental cyst?: Report of a case.
AB  - The mandibular infected buccal cyst occurs on the buccal and distal aspects of
      the roots of the partially or newly erupted first permanent molar. It typically
      affects children between the ages of 6 to 10 years and the associated first
      permanent molar is vital. The cyst is lined with a non-keratinised squamous
      epithelium with inflammatory cell infiltrate in the connective tissue. Most
      clinical and histological features are similar to those reported for paradental
      cysts.

PMID- 8251252
TI  - Orthodontics in The Netherlands.
AB  - In October 1992 I visited the Netherlands and spent time at both university
      training centres and a number of selected specialist orthodontic practices.
      Holland has a population of nearly 15 million and the highest population density
      of any European country. There are about 6,000 GDPs in Holland and about 300
      dentists who have undergone specialty training in orthodontics.

PMID- 8251253
TI  - The professions in the 1990s.
AB  - As they did when they were formed 150 years ago, the professions must again
      convince the public and a cost-conscious and competition-orientated Government
      that they should be entrusted with the provision of services their training has
      made them fit to offer. This article explains why.

PMID- 8251254
TI  - [Post-traumatic psychological disorders].
AB  - Mental disorders after closed-head injury are reviewed. Post-concussive syndrome
      and post-contusional disability are described with particular emphasis on
      consciousness disorders, amnesia, frontal disturbance and long-term outcome.

PMID- 8251256
TI  - [Fractures of the proximal femur: rehabilitation and socioeconomic
      repercussions].
AB  - Only insufficient statistical data for epidemiologic analysis and calculations of
      socioeconomic costs are available in Switzerland. The total number of fractures
      of the proximal femur per year has nearly doubled in the 10 years from 1980 to
      1990, climbing from 5500 to 9800 cases. A number of 15,000 cases is foreseen for
      the year 2020. In 85% of the cases the patients are older than 65 years. The
      global annual incidence is estimated to be 145/100,000, the partial incidence for
      the population of more than 65 years being 825/100,000. The mean hospitalization
      is 30 days. The total number of hospital days per year climbed from 200,000 to
      300,000 in ten years, thus increasing the number of required beds by 50%. The
      mean costs for primary hospitalization is estimated to 15,000.-Swiss francs per
      case in 1990 and 146 Million francs globally per annum, i.e. the double of the
      amount in 1980. In the statistics of the National Accident Insurance Company the
      mean global economic costs for a fracture of the proximal femur in the active
      population is 57,000.-Swiss francs approximately and 72,000.-francs for patients
      of more than 45 years of age. Only roughly 20% of the costs are caused by medical
      treatment, whereas pensions, per diems and other compensations produce 80% of the
      costs. The mortality for patients over 65 varies from 2-7% during the primary
      hospitalization and rises up to 30% after 1 to 2 years after the accident. The
      relationship between the duration of acute hospitalization and rehabilitation is
      essential for planning. The evaluation of the chances for a successful
      rehabilitation is very important, the general medical conditions of the patients
      before the accident being the main determinant factor. A mean hospitalization of
      3 weeks in a surgical unit and 6 to 7 weeks in a rehabilitation hospital seems to
      be realistic. Appropriate criteria for the selection of patients amenable to
      successful rehabilitation are essential. The question of the social outcome of
      these patients should be analyzed on a large scale nationwide study.

PMID- 8251255
TI  - [Management of patient data in an intensive care unit with Macintosh and
      Filemaker Pro--extra effort or facilitation of routine care with improved
      information flow?].
AB  - A documentation system for patients in ICU is presented. The programming is based
      on Filemaker Pro from Claris. Two files have been created: the first "1 Eintritt"
      contains all the patients data like name, address, the patients history,
      diagnosis, therapies as the planned procedures. All these data can be imported
      into the second file "2 KG Unfallchirurgie" with a personal identification
      number. Complications, new results or further procedures can be added. Different
      layouts allow the user to print summaries or duty reports. The experience with
      300 patients showed, that this system is easy to learn and to use, that it has a
      good compliance with the medical staff and that is gains a lot of time writing
      summaries or reports used for transferring patients to other units.

PMID- 8251257
TI  - [Gonarthrosis after injury of the anterior cruciate ligament: a multicenter, long
      term study].
AB  - In order to estimate incidence, severity and associated factors in the
      development of the degenerative arthritis of the knee following a cruciate
      ligament injury, a multicenter, longterm follow-up study was undertaken. The time
      interval between injury and follow-up exam was a minimum of 15 years (range 15-52
      years). Extensive physical examination and radiographic analyses from four "Knee
      Centers" (Hospital for Special Surgery, New York; Orthopadische Klinik,
      Bruderholz; Orthopaedic and Arthritic Hospital, Toronto; Orthopaedic Department
      Wichita, Kansas) on 328 patients revealed that the best correlation to the degree
      of osteoarthritis could be found to the time of meniscectomy. All other
      operations (suture of cruciate ligament, intraarticular or extraarticular
      reconstruction) showed much less correlation to the severity of the degenerative
      arthritis found at the follow-up exam. IN CONCLUSION: Preservation of as much
      meniscus tissue as possible at the time of injury seems to be the best warranty
      for slowing down degenerative arthritis after cruciate ligament injury.

PMID- 8251258
TI  - [Self-injury with liquid nitrogen].
AB  - During an insurance claim case, the question arose as to whether it is possible
      for the lower leg and foot to completely freeze and subsequently suffer necrosis
      if liquid nitrogen is accidentally spilled on them on one single occasion.
      Thermometric and thermographic experiments on corpses revealed that if liquid
      nitrogen is simply poured over a limb, "hoar frost" is formed on the skin but the
      temperature within the limb does not drop. Immersing a limb in liquid nitrogen
      for 40 seconds resulted in the skin becoming frozen, while the temperature within
      the limb only dropped a few degrees. After the limb was removed from the liquid
      nitrogen, it thawed out within 5-8 minutes. CONCLUSION: In this particular case
      we must assume self-affliction by means of direct contact with liquid nitrogen
      over a long period of time. Based on this case the manifestation of acts of self
      infliction and the possibility of proving them is dealt with in more detail.

PMID- 8251259
TI  - [Neuropsychological and psychosocial findings in follow-up of cervical vertebrae
      dislocations: a prospective clinical study].
AB  - A non-selected sample of 117 common whiplash patients was examined shortly after
      experiencing trauma (mean = 7.4 days, SD = 4.2) and six months later with regard
      to neuropsychological performance and psychosocial stress. Neuropsychological
      examination comprised an assessment of various levels of complexity of
      attentional processes. Further, subjective complaints, subjective headache and
      neck pain intensity, utilized medication and self-ratings of well-being and
      cognitive impairment were recorded. In addition, patients were assessed with
      regard to personal history of psychosocial stress and personality traits (e.g.
      neuroticism, depression). At six-month examination, 81 patients subjectively were
      fully recovered, whereas 36 patients reported persisting symptoms. Symptomatic
      patients were older, showed more symptoms at baseline and a higher intensity of
      headache and neck pain, and had a higher subjective cognitive impairment. At
      both, baseline and six-month examination, no significant statistical differences
      between the asymptomatic and symptomatic patients were found with regard to
      cognitive performance. However, performance of symptomatic group in a test of
      divided attention was pathological at baseline. Additionally, symptomatic group
      showed a delayed recovery of cognitive functioning, which could be explained--at
      least in part--by utilized medication and the higher age. This change of
      cognitive equilibrium could account for these patients' cognitive problems in
      daily life.

PMID- 8251260
TI  - Mapping the lateral distribution of photosystem II and the cytochrome b6/f
      complex by direct immune labeling of the thylakoid membrane.
AB  - By direct immunolabeling we have mapped the distribution of photosystem II (PS
      II) and cytochrome b6/f on the surfaces of photosynthetic membranes isolated from
      spinach. Photosynthetic membranes were attached to a support and gently disrupted
      to expose the occluded outer stacked surface, prior to labeling. Polyclonal
      antibodies against PS II intensely labeled the outer stacked surfaces while the
      outer nonstacked surface had minimal labeling. This confirms previous
      fractionation and immunolocalization studies which demonstrated that PS II is
      largely restricted to the stacked regions of the membrane. Inside-out membranes
      were also heavily labeled with PS II antibodies. Antibodies against cytochrome f
      were evenly distributed between the stacked and nonstacked outer surfaces and
      were found clumped together on the membrane outer surface. Previous fractionation
      and immunolocalization studies have indicated that cytochrome b6/f is located in
      both the stacked and nonstacked regions, but this is the first report to provide
      direct evidence that the complex may be clustered in the membrane. The clustering
      of antibodies to cytochrome b6/f supports the idea that this electron transport
      component exists as a multimeric complex within the membranes and that such
      complexes are found in both stacked and nonstacked regions of the photosynthetic
      membrane. No evidence was seen of any special differentiation of the marginal
      regions of the membrane, which link stacked and nonstacked regions.

PMID- 8251261
TI  - Direct visualization of myosin filament symmetry in tarantula striated muscle by
      electron microscopy.
AB  - Chemically demembranated bundles of fibers from tarantula leg muscle were rapidly
      frozen in the relaxed state and freeze-substituted in the presence of tannic
      acid. Electron micrographs of thin transverse sections of freeze-substituted
      specimens frequently showed four clear, regularly organized projections
      (crossbridges) protruding from the backbones of the myosin filaments and
      partially wrapping around the filament surface. The rotational power spectra of
      individual filaments showed a peak at N = 4. Alignment and averaging of the
      images using correlation methods confirmed the fourfold symmetry and the slewed
      configuration of the crossbridges on the filament surface. These observations
      directly reveal essential features of the low-resolution three-dimensional
      helical reconstruction of negatively stained tarantula filaments calculated
      previously (R. A. Crowther, R. Padron, and R. Craig, 1985, J. Mol. Biol. 184, 429
      439).

PMID- 8251262
TI  - Electron microscopy of human erythrocyte catalase: new two-dimensional crystal
      forms.
AB  - Using the mica-spreading "negative staining-carbon film" procedure, human
      erythrocyte catalase has been shown to create a number of different periodic or
      crystalline two-dimensional (2-D) arrays which differ in the arrangement of
      molecules in the repeating units and the lattice type. Digital image processing
      has been performed with a 2-D array which contains regularly arranged
      "undulating" rows of molecules and also with a 2-D crystal form, exhibiting pgg
      (p22(1)2(1)) symmetry and lattice parameters of a = 12.7 nm, b = 44 nm, and gamma
      = 92 degrees. The data are compared with our previous analysis of a different
      human erythrocyte catalase 2-D crystal, and the effect of partial-depth negative
      staining occurring in all the various 2-D forms is discussed.

PMID- 8251263
TI  - Cytoskeleton architecture of C6 rat glioma cell subclones differing in
      intermediate filament protein expression.
AB  - Whole-mount electron microscopy was used in conjunction with immunogold labeling
      to characterize the cytoskeleton architecture of C6 rat glioma cell subclones.
      These subclones differ in intermediate filament (IF) protein composition and
      either contain vimentin (subclone C6D8) or do not express any of the known
      cytoplasmic IF proteins (subclone C6D10) (Roser et al., 1991). In C6D8 cells
      short thin (3 nm) connecting filaments frequently linked vimentin to actin
      filaments and, in addition, connected vimentin filaments to each other.
      Occasionally, direct contacts were noticed between actin and vimentin filaments.
      Thin connecting filaments were present at a significantly higher number in IF
      deficient C6D10 cells, forming a dense cytoplasmic network in conjunction with
      actin filament bundles as the dominating structure. The data indicate that thin
      connecting filaments are present in C6 cells independent of the expression of
      cytoplasmic IF proteins. They suggest that structural linkages between vimentin
      and actin filaments mediated by thin connecting filaments could play a major role
      in determining the cytoskeleton architecture of these cells.

PMID- 8251264
TI  - A dual role for involucrin in the epidermis-ultrastructural localization in
      epidermis and hair follicle in humans and transgenic mice.
AB  - Transgenic mice expressing human involucrin (hINV) have an abnormal hair coat
      appearance. To understand this phenotype, we used immunoelectron microscopy to
      examine hINV distribution in the hair follicle and epidermis. In human epidermis,
      hINV is first observed in the cytoplasm of spinous and granular layer cells. In
      transition cells, it is equally distributed between the cytoplasm and the nascent
      cornified envelope, while in the corneocytes it is largely cornified envelope
      associated. In transgenic mice, the pattern of expression is similar except that
      much more antigen appears to be present. An important finding is the presence of
      hINV in hair follicle structures--low levels in the hair and high levels in the
      inner root sheath (IRS). The distribution of hINV is comparable in human and
      transgenic mouse follicles; however, much higher levels are observed in the mice.
      In contrast, hINV is not detected in cells of the outer root sheath (ORS). Thus,
      hINV is differentially expressed in two related and contiguous tissues, the
      epidermis and the ORS. Based on these results we conclude that hINV is a specific
      product of differentiated IRS cells that is localized at the cell envelope,
      suggesting a function as a cross-linked constituent of IRS cell envelope. These
      results suggest that hINV may have a dual role in epidermis, as a cross-linked
      structural protein in the epidermal corneocyte and the hair follicle IRS.

PMID- 8251265
TI  - Acrosome reaction in ascidians induced by a calcium ionophore.
AB  - Ca ionophore A23187 induces an acrosome reaction in Ciona intestinalis and
      Halocynthia roretzi spermatozoa. This process occurs by the fusion of the
      acrosomal outer membrane along its peripheral margin with the plasma membrane
      overlying the acrosome. The fusion process leads to the exocytosis of the
      acrosomal contents and results in the formation of a vesicle bounded by membrane
      made up of the acrosomal outer membrane and the overlying plasma membrane that is
      eventually shed. The acrosomal inner membrane is exposed and becomes a part of
      the plasma membrane enclosing the anterior region of the sperm head. The chemical
      nature and the precise role of the acrosomal contents at fertilization must await
      further studies.

PMID- 8251266
TI  - 4-A projection map of bacteriophage T4 DNA helix-destabilizing protein (gp32*I)
      crystal by 400-kV electron cryomicroscopy.
AB  - Ice-embedded crystals of bacteriophage T4 DNA helix-destabilizing protein gp32*I
      were imaged by computer-controlled spot-scanning on a 400-kV electron
      cryomicroscope. gp32*I crystals generally have different steps of thickness
      within a crystal; each step can have different symmetry. Multivariate statistical
      analysis enabled us to unambiguously select spot-scan images that consist
      entirely of one motif which were processed subsequently by crystallographic
      Fourier-averaging techniques. The computed phases of the resulting reflections
      were evaluated for symmetry in projection, and some of those images were
      correlated with independent thickness measurements of freeze-dried samples of the
      same crystals. The structure factors with pgg symmetry from nine spot-scan images
      were merged, and the mean figure of merit of merged phases was better than 0.9
      for data at resolution up to 4 A. A projection map was generated and showed
      multiple density peaks that corresponded to the high-resolution features of
      gp32*I.

PMID- 8251267
TI  - Aspirin-induced asthma.

PMID- 8251268
TI  - Effects of increasing doses of alfentanil, fentanyl and morphine on mid-latency
      auditory evoked potentials.
AB  - We have studied dose-dependent effects of alfentanil, fentanyl and morphine on
      mid-latency auditory evoked potentials (MLAEP). Anaesthesia was induced with
      alfentanil 100 micrograms kg-1 every 5 min to a total dose of 500 micrograms kg-1
      (group I, n = 10), fentanyl 10 micrograms kg-1 every 7 min to a total dose of 50
      micrograms kg-1 (group II, n = 10) or morphine 1 mg kg-1 for induction and 0.5 mg
      kg-1 every 15 min to a total dose of 3 mg kg-1 (group III, n = 10). MLAEP were
      recorded before and 3-15 min after every opioid dose on vertex (positive) and
      mastoids on both sides (negative). Latencies of the peaks V, Na, Pa, Nb, P1 (ms)
      and amplitudes Na/Pa, Pa/Nb and Nb/P1 (microV) were measured. Fast-Fourier
      transformation was used to calculate power spectra of the AEP. In the awake
      state, MLAEP had high peak-to-peak amplitudes and a periodic waveform. Power
      spectra indicated high energy in the 30-40 Hz frequency range. During general
      anaesthesia with increasing doses of alfentanil, fentanyl and morphine, the
      brainstem response V was stable. There was a marked increase only in latency and
      decrease in amplitude of P1. In contrast, for the early cortical potentials Na
      and Pa, only small increases in latencies and decreases in amplitudes were
      observed. After the largest doses of alfentanil (500 micrograms kg-1), fentanyl
      (50 micrograms kg-1) and morphine (3 mg kg-1), Na, Pa and Nb showed a similar
      pattern as in awake patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251269
TI  - Mid-latency auditory evoked potentials during ketamine anaesthesia in humans.
AB  - We studied mid-latency auditory evoked potentials (MLAEP) during induction of
      general anaesthesia with ketamine 2 mg kg-1. MLAEP were recorded before, during
      and after induction of general anaesthesia on the vertex (positive) and mastoid
      (negative) positions. Latencies of the peak V, Na, Pa, Nb, P1 and amplitudes
      Na/Pa, Pa/Nb and Nb/P1 were measured. Fast-Fourier transformation was used to
      calculate power spectra of the MLAEP. In the awake state, MLAEP had large peak-to
      peak amplitudes and a periodic waveform. Peak latencies remained within the
      normal range. Power spectra indicated high energy in the 30-40 Hz frequency
      range. After induction of general anaesthesia with ketamine, there was no change
      in latency of peaks V, Na, Pa, Nb, P1 and no apparent reduction in amplitudes
      Na/Pa, Pa/Nb and Nb/P1. In the power spectra, frequencies in the range of 30-40
      Hz retained high energy. Amplitudes and latencies of MLAEP did not change during
      induction of general anaesthesia with ketamine. Primary processing of auditory
      stimuli in the primary auditory cortex seemed to be preserved under ketamine.
      Suppression of sensory (auditory) information processing must take place at a
      higher cortical level in a dissociative manner.

PMID- 8251270
TI  - A measure of consciousness and memory during isoflurane administration: the
      coherent frequency.
AB  - The coherent frequency (CF) of the auditory evoked response (AER) is derived
      using auditory clicks presented at frequencies in the range 5-47 Hz. CF and
      psychological performance were measured while seven subjects breathed isoflurane
      in doses increasing from 0% to 0.2%, 0.4% and 0.8% end-tidal concentration and
      then decreasing to 0%. With increasing doses of isoflurane, CF decreased and
      there was a decrease in within-list recognition (WLR) and category recognition
      (CR) scores. There was a correlation between changes in CF and WLR (P < 0.05) and
      between CF and category recognition (CR) (P < 0.05). A painful stimulus given in
      conjunction with 0.4% isoflurane caused an increase in CF, WLR and CR in some
      subjects. This did not reach statistical significance for the group as a whole,
      apart from the short word interval scores in the WLR which indicated an increase
      in attention (P < 0.01). Subjects did not respond with 0.8% isoflurane, either
      before or after painful stimulation. Reduction of end-tidal isoflurane from 0.8%
      to 0% caused an increase in the CF and improved performance on the psychological
      tests. A category generation task on recovery showed no evidence of implicit
      learning of words presented in conjunction with 0.8% isoflurane.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8251271
TI  - Effect of a sub-anaesthetic concentration of halothane on the ventilatory
      response to sustained hypoxia in healthy humans.
AB  - We selected nine normal subjects (8M, 1F; aged 25-43 yr) with brisk hypoxic
      ventilatory responses, and studied their ventilatory response to sustained
      isocapnic hypoxia (SaO2 82 (SEM 0.1) % for 25 min) in the presence and absence of
      0.1% inspired halothane. Halothane had no significant effect on baseline
      ventilation or gas exchange. In the absence of halothane, ventilation increased
      initially from mean 7.57 (0.35) litre min-1 to 14.54 (0.91) litre min-1, and
      decreased subsequently to 10.74 (0.32) litre min-1 during hypoxia (both P <
      0.05). In the presence of 0.1% inspired halothane, ventilation increased
      initially from 7.19 (0.47) litre min-1 to 12.08 (0.99) litre min-1 (P < 0.05),
      then decreased to 10.12 (0.28) litre min-1 during sustained hypoxia (ns compared
      with baseline normoxic ventilation). Halothane reduced significantly the initial
      increase in ventilation (P < 0.05), but did not enhance the subsequent decrease.
      These results confirm that a sub-anaesthetic concentration of halothane depresses
      the initial hypoxic ventilatory response; the response during prolonged periods
      of hypoxia is, however, less than the initial response and is reduced in the
      presence or absence of a sub-anaesthetic concentration of halothane.

PMID- 8251272
TI  - Comparison of the effects of the laryngeal mask airway and endotracheal
      intubation on vocal function.
AB  - We have compared changes in vocal function produced after insertion of a
      laryngeal mask airway (LMA) with those produced by tracheal intubation in 20
      patients. Using acoustic waveform analysis, we computed amplitude variability
      (AV), pitch variability (PV), harmonics-to-noise ratio (HNR) and additive noise
      level (ANL) before anaesthesia and at 1, 4, and 24 h after tracheal extubation.
      There were no significant changes in vocal function after extubation except for
      HNR ratio (P = 0.046) at 4 h in the LMA group. There were differences in all four
      variables at 1 h, 4 h, or both, after tracheal extubation compared with baseline
      in the tracheal tube group. In both groups, all variables were the same as
      baseline values 24 h after extubation. We observed significant differences in AV
      (4 h), PV and ANL (1, 4 h) values between the two groups. These observations
      suggest that the LMA causes less vocal change than tracheal intubation.

PMID- 8251273
TI  - Comparison of 0.125% bupivacaine with 0.125% bupivacaine and clonidine as
      extradural analgesia in the first stage of labour.
AB  - We have studied 42 healthy parturients with singleton vertex pregnancies, who
      were in the first stage of labour and requesting extradural analgesia. They were
      allocated randomly in a double-blind fashion to receive either 0.125% bupivacaine
      plain or 0.125% bupivacaine with clonidine 120 micrograms. Efficacy of analgesia
      was evaluated using linear visual analogue scoring (VAS), sensory block was
      assessed using bilateral pinprick in the mid-clavicular line and sedation scored
      on a five-point scale. Maternal and fetal cardiovascular variables were measured
      every 2 min for 20 min, at 30 min and subsequently at 15-min intervals. The
      reduction in VAS was greater at all times in the bupivacaine-clonidine group (P <
      0.01). The median (range) duration of analgesia was greater in the bupivacaine
      clonidine group (114.5 (30-243) min) compared with the bupivacaine group (53 (30
      100) min) (P < 0.001). Analgesia was associated with a reduction in arterial
      pressure in both groups, but there were no between-group differences. Maternal
      heart rate was less than baseline values at 30-90 min in the bupivacaine
      clonidine group only. Sedation was greater in the bupivacaine-clonidine group,
      especially from 15 to 45 min (P < 0.01). There were no differences in fetal heart
      rate, mode of delivery or Apgar scores between the two groups.

PMID- 8251274
TI  - Clonidine combined with sufentanil and bupivacaine with adrenaline for obstetric
      analgesia.
AB  - Clonidine produces analgesia via a non-opioid mechanism and it may be used as an
      interesting adjuvant to local anaesthetics and opioids in obstetric analgesia. To
      examine the effects of the addition of clonidine to bolus injections of
      bupivacaine, adrenaline and sufentanil, we enrolled 50 women receiving extradural
      analgesia for vaginal delivery into a double-blind study. They were allocated
      randomly to two groups: group A received a 10-ml extradural solution of
      bupivacaine 12.5 mg combined with adrenaline 25 micrograms and sufentanil 10
      micrograms; group B received the same solution with clonidine 30 micrograms. Each
      patient was allowed two subsequent injections of the chosen solution.
      Subsequently, if still in the first stage of labour, analgesia was augmented with
      additional 10-ml injections of bupivacaine 12.5 mg with adrenaline 25 micrograms,
      without sufentanil or clonidine. The latter solution was used for perineal
      analgesia in group A; clonidine 30 micrograms was added in group B. During the
      first and second stages of labour, there was no difference between the two groups
      in duration of analgesia after the first injection (142 min in group A; 127 min
      in group B), number of injections (1.8 in group A; 1.9 in group B) and the total
      bupivacaine requirements (33.9 mg in group A; 34 mg in group B). The quality of
      analgesia was evaluated as very good in both groups (23/25 in group A; 24/25 in
      group B). The degree of motor block or the frequency of other side effects were
      not enhanced by clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251275
TI  - Comparison of the analgesic effects of intrathecal clonidine and intrathecal
      morphine after spinal anaesthesia in patients undergoing total hip replacement.
AB  - We have studied the anaesthetic and analgesic properties of intrathecal clonidine
      and intrathecal morphine in patients undergoing total hip replacement under
      spinal anaesthesia. After routine spinal anaesthesia with 0.5% plain bupivacaine
      2.75 ml, patients were allocated randomly to receive intrathecal clonidine,
      morphine or saline (control) as adjuvant to the bupivacaine. Postoperative
      analgesic effects were measured by consumption of morphine via patient-controlled
      analgesia and visual analogue pain scores. Both intrathecal clonidine and
      intrathecal morphine prolonged the time to first analgesia compared with saline
      (mean 278 (SD 93.2) min, 498 (282.4) min and 54 (61.9) min, respectively) (P <
      0.001). Total morphine consumption on the first night after operation was
      significantly less in the intrathecal morphine group. There were no differences
      between the clonidine and the control group. Intrathecal clonidine prolonged the
      duration of spinal analgesia, but was markedly inferior to the intrathecal
      morphine in providing subsequent postoperative analgesia.

PMID- 8251276
TI  - Single-dose, randomized, double-blind, double-dummy cross-over comparison of
      extradural and i.v. clonidine in chronic pain.
AB  - We studied 10 patients with chronic back pain who had claimed benefit with a
      previous extradural dose of clonidine 150 micrograms combined with local
      anaesthetic. We compared a single dose of clonidine 150 micrograms given by
      either the extradural or i.v. route in a double-blind, randomized, double-dummy
      and cross-over fashion, with 80% power to detect a difference in the analgesic
      effect of the two routes. Pain intensity, pain relief, adverse effects, mood,
      sedation and vital signs were assessed by a nurse observer. I.v. clonidine
      produced significantly (P < 0.04) greater analgesia than extradural clonidine in
      one of the five analgesic outcome measures. Clonidine given by either route
      produced statistically significant sedation and significant decreases in arterial
      pressure and heart rate. In this study, extradural clonidine had no significant
      clinical advantages compared with i.v. clonidine; clonidine 150 micrograms by
      either route produced a high incidence of adverse effects.

PMID- 8251277
TI  - Comparison of patient-controlled analgesia with and without a background infusion
      after lower abdominal surgery in children.
AB  - Forty children aged 6-12 yr undergoing appendicectomy were allocated randomly to
      receive postoperative i.v. morphine by a patient-controlled analgesia (PCA)
      system (bolus dose 20 micrograms kg-1 with a lockout interval of 5 min) or the
      same PCA with a background infusion of morphine 20 micrograms kg-1 h-1. Patients
      breathed air and oxygen saturation was monitored by continuous pulse oximetry.
      Scores for pain, sedation and nausea were recorded hourly. Patients with PCA +
      background infusion received significantly more morphine than those with PCA
      only. Both groups self-administered similar amounts of morphine using the PCA
      machine. There were no significant differences in the pain scores of the two
      groups. Patients with PCA+background infusion suffered more nausea (P < 0.01),
      more sedation (P < 0.05) and hypoxaemia (P < 0.001) than those with PCA only.
      They also had a better sleep pattern than those with PCA only.

PMID- 8251278
TI  - Effect of alcohol on gastric emptying in volunteers.
AB  - We have examined the effect of alcohol on the gastric emptying rate of a liquid
      meal in 10 volunteers. Each volunteer was allocated randomly to receive, on three
      occasions, no alcohol, 3 units or 6 units of alcohol. Gastric emptying was
      measured using applied potential tomography. The rate of gastric emptying as
      measured by the time to 50% emptying (T50) was delayed significantly (P < 0.01)
      after alcohol 6 units (median 45.0 min (range 19-90 min)) compared with control
      (23.0 min (13-36 min)) and there was little change after alcohol 3 units (25.5
      min (10-65 min)) [corrected].

PMID- 8251279
TI  - Tropisetron for postoperative nausea and vomiting in patients after
      gynaecological surgery.
AB  - In a double-blind study, we have compared the prophylactic antiemetic effect of
      tropisetron 5 mg (Navoban, a 5-HT3 receptor antagonist) with that of placebo,
      both given as a short i.v. infusion approximately 15 min before wound closure in
      patients undergoing gynaecological surgery. Perioperative anaesthetic care was
      standardized and patients were observed for at least 24 h after operation. The 35
      patients given tropisetron and 34 given placebo treatment were well matched for
      characteristics. Vomiting occurred in 26% of tropisetron-treated patients,
      compared with 59% of placebo-treated patients (P = 0.006); 69% of tropisetron
      treated patients suffered nausea, compared with 88% of placebo-treated patients
      (P = 0.05). In addition, patients judged the antiemetic treatment with
      tropisetron as more effective than the placebo treatment (visual analogue score
      71 vs 51 mm (P = 0.003)).

PMID- 8251280
TI  - Effect of tropisetron, a 5-HT3 receptor antagonist, on analgesia and nausea after
      intrathecal morphine.
AB  - We have studied the effect of tropisetron, a 5-HT3-receptor antagonist, on
      postoperative nausea, vomiting and pain in 54 patients, aged 50-83 yr, after
      major hip or knee surgery. The patients were given subarachnoid injection of
      plain 0.5% bupivacaine, mixed with preservative-free morphine 0.3 mg, for
      surgical and postoperative analgesia. In a double-blind fashion, either
      tropisetron 5 mg (1 mg ml-1) or saline 5 ml was injected i.v. 30 min after spinal
      administration of bupivacaine and morphine. The number of patients needing i.m.
      oxycodone for pain relief, the total number of oxycodone doses or the mean time
      to the first i.m. oxycodone administration did not differ significantly between
      the two groups. The number of patients who became nauseated or vomited during the
      observation period did not differ significantly between groups. Seventeen
      patients had nausea and 11 vomited in the tropisetron group, compared with 20 and
      13, respectively, in the control group during the first 24 h.

PMID- 8251281
TI  - Double-blind comparison between doxapram and pethidine in the treatment of
      postanaesthetic shivering.
AB  - Sixty patients who shivered after routine surgery under general anaesthesia were
      allocated randomly to receive normal saline (n = 20), doxapram 1.5 mg kg-1 (n =
      20) or pethidine 0.33 mg kg-1 (n = 20). Both doxapram and pethidine were
      effective in treating postoperative shivering 2-3 min after i.v. administration.
      In the group who received normal saline, 15 patients were still shivering 10 min
      after treatment, whilst in the doxapram group only three patients were shivering
      at that time. In the pethidine group, all patients had stopped shivering by 7 min
      after treatment. We conclude that both doxapram and pethidine were effective in
      the treatment of postoperative shivering.

PMID- 8251282
TI  - Spectral characteristics of embolic heart sounds detected by precordial Doppler
      ultrasound during venous air embolism in dogs.
AB  - We have studied the frequency spectrum of embolic heart sounds as detected by
      precordial Doppler ultrasound after injecting air 0.01-0.1 ml into the external
      jugular vein of anaesthetized dogs (n = 7). At volumes of 0.05 ml and greater,
      there was a significant increase in both the maximum frequency of the spectrum
      and the power of those high frequency components to greater than control values.
      Both changes correlated significantly with the volume of air injected (P < 0.05).
      With repeated injections of air at 5-min intervals, there was a small increase in
      the high frequency components in the control signal between injections (P <
      0.05). We conclude that such spectral changes could be used to quantify the
      volume of air in transit through the heart, and to reflect the short-term history
      of venous air embolism.

PMID- 8251283
TI  - Cardiovascular effects of isoflurane and halothane in young and elderly adult
      patients.
AB  - We have studied the cardiovascular effects of 1 MAC end-tidal concentrations of
      halothane and isoflurane in young (n = 40) and elderly (n = 40) adult patients
      using non-invasive techniques. Cardiac output was measured by Doppler
      ultrasonography. Halothane reduced heart rate, systolic, mean and diastolic
      arterial pressures and cardiac index in both age groups (P < 0.05). Isoflurane
      reduced systolic, mean and diastolic arterial pressures also, but reduced cardiac
      index and heart rate only in the older patients (P < 0.05). Halothane depressed
      cardiovascular state significantly more than isoflurane in the younger adults (P
      < 0.05), but cardiovascular depression was similar for the two agents in the
      older age group. The decreases in systolic and diastolic pressures in the older
      patients were significantly greater with isoflurane compared with halothane (P <
      0.05).

PMID- 8251284
TI  - Dose-response relationship for inhaled nitric oxide in experimental pulmonary
      hypertension in sheep.
AB  - We have examined the effect of inhaled nitric oxide 4-512 p.p.m. in six sheep
      with pulmonary hypertension induced first with hypoxia and then with 6 micrograms
      kg-1 of E. coli endotoxin. A similar dose-dependent reduction in pulmonary artery
      pressure occurred in pulmonary hypertension induced by hypoxia or endotoxin, with
      a maximum effect of 25-30% decrease with nitric oxide 64 p.p.m. Increasing the
      dose to 512 p.p.m. had no further effect. The ED50 for inhaled nitric oxide was
      39 p.p.m. for pulmonary hypertension induced by hypoxia and 48 p.p.m. for
      endotoxin-induced pulmonary hypertension. A dose-dependent increase in arterial
      oxygenation, which reached a maximum with nitric oxide 64 p.p.m., was seen with
      inhaled nitric oxide after endotoxin infusion. If the toxicity of inhaled nitric
      oxide can be determined, it may prove useful in the treatment of pulmonary
      hypertension secondary to the adult respiratory distress syndrome.

PMID- 8251285
TI  - Dose-response relationships for edrophonium and neostigmine antagonism of
      mivacurium-induced neuromuscular block.
AB  - We have studied the dose-response relationships for neostigmine and edrophonium
      during antagonism of neuromuscular block induced by mivacurium chloride. Sixty
      four ASA group I or II adults were given mivacurium 0.15 mg kg-1 during fentanyl
      thiopentone-nitrous oxide-isoflurane anaesthesia. Train-of-four stimulation (TOF)
      was applied to the ulnar nerve every 10 s, and the force of contraction of the
      adductor pollicis muscle was recorded. When spontaneous recovery of first twitch
      height reached 10% of its initial control value, edrophonium 0.1, 0.2, 0.4, or 1
      mg kg-1 or neostigmine 0.005, 0.01, 0.02, or 0.05 mg kg-1 was administered by
      random allocation. Neuromuscular function in another 16 subjects was allowed to
      recover spontaneously. Spontaneous recovery from 90% mivacurium block to 95%
      twitch height and TOF ratio 0.75 occurred within 15 min. This study demonstrated
      that the dose-response curves for these two drugs for antagonism of neuromuscular
      block (first twitch and train-of-four ratio) were parallel. The doses of
      neostigmine required to achieve 50% (ED50) and 70% (ED70) recovery of the first
      twitch after 10 min were 2 (1.5-2.5) micrograms kg-1 and 4.7 (4.1-5.4) micrograms
      kg-1 (mean (95% confidence intervals)), respectively. Corresponding ED50 and ED70
      values for edrophonium were 2.8 (0.75-10.2) micrograms kg-1 and 9.2 (3.6-23.6)
      micrograms kg-1, respectively. These values corresponded to
      neostigmine:edrophonium potency ratios of 1.4 (0.4-2.4) and 1.95 (0.9-2.9) for
      first twitch ED50 and ED70 height, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251286
TI  - Comparison of propofol with thiopentone for treatment of bupivacaine-induced
      seizures in rats.
AB  - Thirty Sprague-Dawley rats were paralysed with pancuronium and their lungs
      ventilated mechanically with 70% nitrous oxide and 0.5% halothane in oxygen.
      Bupivacaine 2 mg kg-1 min-1 was infused continuously i.v. until the animals died.
      At the onset of seizures, animals were given an i.v. bolus of propofol 1 mg kg-1
      (n = 10), thiopentone 2 mg kg-1 (n = 10) or lipid vehicle (n = 10).
      Administration of propofol or thiopentone was repeated each time seizures
      restarted and lipid vehicle administrations were repeated at 2-min intervals
      until the electroencephalogram became isoelectric. All animals developed
      seizures, arrhythmias, isoelectric EEG and asystole. Administration of lipid
      vehicle induced no obvious changes in ongoing epileptiform activity. The initial
      doses of thiopentone and of propofol stopped epileptiform activity in all
      animals, usually within 6 s after administration. The seizure-free period after
      the initial administration of thiopentone and of propofol lasted, on average,
      0.98 min and 1.72 min, respectively. We conclude that propofol may have value in
      treating seizures induced by bupivacaine.

PMID- 8251287
TI  - Pulmonary vascular effects of trinitroglycerin and isosorbide dinitrate after
      cardiopulmonary bypass.
AB  - We have compared the systemic and right ventricular haemodynamic effects of
      trinitroglycerin (TNG) and isosorbide dinitrate (ISDN) in patients recovering
      from coronary artery bypass grafting. Each of the 16 patients was given
      increasing i.v. doses of the two nitrates in a random order and double blind
      fashion until the target of a 25% decrease in mean pulmonary artery pressure
      (MPAP) was achieved. Total doses of TNG 9 (6-12) micrograms kg-1 (mean, 95%
      confidence interval) and ISDN 148 (76-220) micrograms kg-1 were given during
      infusions of 22 (18-25) min and 34 (28-41) min duration, respectively. The target
      decrease in MPAP was produced with infusion rates of TNG 0.5 (0.4-0.7) micrograms
      kg-1 min-1 and ISDN 5.8 (4.1-7.5) micrograms kg-1 min-1. These doses produced
      similar acute decreases in MPAP and similar effects on pulmonary and systemic
      vascular resistances and systemic and right ventricular haemodynamic variables.
      We conclude that TNG is more than 10 times as potent as ISDN in its acute
      haemodynamic effects in cardiac surgical patients in the immediate postoperative
      period. Both nitrates have relatively greater effects on the pulmonary than the
      systemic vasculature.

PMID- 8251288
TI  - Acute effects of obstructive sleep apnoea.

PMID- 8251289
TI  - Comparison of end-tidal and arterial carbon dioxide measurements during
      anaesthesia with the laryngeal mask airway.
AB  - We have confirmed the value of measurement of end-tidal carbon dioxide
      concentration as an indicator of arterial carbon dioxide tension during the use
      of the laryngeal mask airway in healthy patients breathing spontaneously. The
      mean difference between arterial and end-tidal carbon dioxide tension was 0.52
      kPa (range 0-1.5 kPa), which is similar to the difference which has been reported
      when a tracheal tube has been used.

PMID- 8251290
TI  - Effect of atropine on the QT interval and T-wave amplitude in healthy volunteers.
AB  - Prolongation of the QT interval of the ECG represents an imbalance in cardiac
      autonomic function and may predict cardiac arrhythmia. Vagal activity protects
      against prolongation of the QT interval which may be associated with flattening
      of the T-wave of the ECG. The changes in QT interval, T-wave amplitude and
      respiratory sinus arrhythmia (RSA) were studied after i.v. administration of
      atropine 20 micrograms kg-1 or placebo to 10 healthy volunteers in a cross-over
      study. After atropine, a decrease in RSA occurred in all volunteers, but remained
      at baseline values after placebo. Corrected QT interval (QTc) increased from 410
      (20) ms to 454 (11) ms (P < 0.001) 5 min after atropine and remained prolonged
      for the entire study period (60 min). The T-wave flattened significantly
      (measured as R:T ratio) up to 30 min, without any changes in the R-wave. No
      changes in the ECG occurred with placebo.

PMID- 8251291
TI  - Norpethidine toxicity and patient controlled analgesia.
AB  - Patient-controlled analgesia (PCA) with i.v. opioids is prescribed increasingly.
      We report three cases of norpethidine toxicity in patients receiving pethidine by
      PCA.

PMID- 8251292
TI  - Efficiency of breathing systems A and D in the Carden Ventmasta ventilator.
AB  - We have compared the efficiency of the enclosed Magill attachment (System A) and
      the co-axial System D (Bain) in the Carden Ventmasta ventilator using both
      systems, each under five different ventilatory conditions, in each of five
      anaesthetized patients. Efficiency was assessed in terms of the effective
      alveolar ventilation as a fraction of the fresh gas flow. For System A,
      efficiency increased from a mean of 0.37 when the total ventilation was only 50%
      of the fresh gas flow, to a mean of 0.74 when ventilation was 2.3 times the fresh
      gas flow. The efficiency was substantially and significantly less with System D:
      75% of that for System A at the smaller total ventilation (95% CI 65-85%) and 65%
      at the larger (95% CI 59-71%). A critical examination is made of conflicting
      definitions and terminology of the efficiency of breathing systems.

PMID- 8251293
TI  - Continuous spirometry: an aid to monitoring ventilation during operation.
AB  - We present six case-reports of patients who experienced inadequate ventilation as
      a result of endobronchial or oesophageal intubation, or obstruction to the
      tracheal tube or airway and were monitored with on-line spirometry. The
      continuously displayed pressure-volume or flow-volume loops may be compared with
      previously recorded baseline loops. The changing configuration of the curves
      offers additional and instantaneous information about the cause of increased
      inspiratory airway pressure, decreased compliance or increased airway resistance.
      Monitoring flow-volume and pressure-volume loops in conjunction with currently
      available techniques provides a comprehensive method of monitoring ventilation.

PMID- 8251294
TI  - Postoperative analgesia in children using continuous s.c. morphine.
AB  - Sixty children (7 months-20 yr; mean 6.5 yr, median 7-8 yr, mode 1-2 yr)
      undergoing major surgery received a balanced technique of general anaesthesia
      combined with bupivacaine as a single injection extradural or peripheral nerve
      block. Postoperative analgesia consisted of a subcutaneous infusion of morphine 1
      mg kg-1 body weight in 20 ml of normal saline [corrected] at a rate of 0.3-0.5 ml
      h-1, controlled by the nursing staff in the surgical ward. Monitoring included
      SpO2, pain, sedation and nausea/vomiting scores. Infusions were used for a mean
      of 38.8 h (range 17-80 h). Ninety-seven percent of recordings of SpO2 were
      greater than 94% and only one recording in 2361 was less than 90%. Ninety-four
      percent of pain scores indicated either no pain or slight pain; 1% indicated
      severe pain. On the order of the medical staff, seven children had the rate of
      infusion of morphine increased to 0.6 ml h-1 [corrected] because of high pain
      scores. Sedation scores compatible with children being either awake or asleep but
      rousable by speech alone were recorded on 99.7% of occasions. No child at any
      time was unrousable. Of 1248 nausea/vomiting scores, only 2.8% indicated the
      presence of these side effects; in only two children were they thought to be
      troublesome. As a result of this audit, nursing staff have been permitted to
      increase the rate of infusion of morphine to 0.6 ml h-1 [corrected] if required.

PMID- 8251295
TI  - The laryngeal mask for intraocular surgery.

PMID- 8251296
TI  - The laryngeal mask for intraocular surgery.

PMID- 8251297
TI  - Tracheal tube cuff inflation as an aid to blind nasotracheal intubation in a
      patient with cervical spine injury.

PMID- 8251298
TI  - Spinal needle: an unusual complication.

PMID- 8251299
TI  - Analgesia induced by metoclopramide.

PMID- 8251300
TI  - Sore throat after suxamethonium.

PMID- 8251301
TI  - Postdural puncture headache and extradural blood patch.

PMID- 8251302
TI  - Growth of Listeria monocytogenes, Aeromonas hydrophila and Yersinia
      enterocolitica in pate and a comparison with predictive models.
AB  - A reference or type strain and a food derived-strain of the cold-tolerant
      pathogens Listeria monocytogenes, Aeromonas hydrophila and Yersinia
      enterocolitica were individually inoculated into samples of commercial pate and
      incubated at 4 and 10 degrees C. The organisms were periodically estimated by
      presumptive counts, then values for the lag and generation times were calculated.
      Both strains of L. monocytogenes grew at both temperatures. The food strain of A.
      hydrophila grew only at 10 degrees C, and the type strain did not grow at either
      temperature. Similarly, the type strain of Y. enterocolitica did not grow at
      either temperature, whereas the food strain grew at both 4 and 10 degrees C. In
      some cases growth of non-test organisms may have inhibited the growth of these
      latter two species. The measured values of lag and generation times did not, in
      general, correlate well with those predicted by response surface models, taken
      from the literature and produced in this laboratory. It may be that the pate
      contained an inhibitor that affected the growth of the organisms. The two strains
      of A. hydrophila and Y. enterocolitica showed significantly different growth
      characteristics, reinforcing the value of using a 'cocktail' of strains in growth
      experiments. Differences in predicted kinetic values from the models indicate
      that a model for any particular strain may not reflect the growth of naturally
      occurring contaminants of the same species.

PMID- 8251303
TI  - Properties of Bacillus cereus spores in reference materials prepared from
      artificially contaminated spray dried milk.
AB  - A reference material for Bacillus cereus was developed based on spray drying of
      milk artificially contaminated with B. cereus spores. Various properties of the
      B. cereus spores in the milk powder were determined. The stability of the
      materials was good with no detectable decrease in the contamination level during
      1 1/2 years storage at -20 degrees C or 4 weeks at 22, 30 or 37 degrees C. The
      homogeneity of the material was found acceptable for use as a reference material.
      Heat treatments (10 min at 70 or 80 degrees C) and addition of lysozyme to the
      enumeration medium did not influence the number of spores counted. The
      germination of the spores depended on the type of medium in which the milk powder
      was reconstituted, and on the storage period of the material. The suitability of
      the material was confirmed in a collaborative study. From the results obtained it
      was concluded that the material developed meets the general requirements set for
      reference materials and can therefore be used for, among others, testing
      laboratory performance.

PMID- 8251304
TI  - Evaluation of bacterial contamination at separate processing stages in emulsion
      sausage production.
AB  - The contamination with spoilage bacteria at separate production steps during the
      production of emulsion sausages was evaluated using a special sampling and
      evaluation method. Heat processed and chilled sausages were aseptically
      transferred directly to cold storage, cutting down or packing. Upon completion of
      the particular production step the sausages were vacuum-packed and stored at 8
      degrees C. During storage, the microbial growth of the sausages was followed and
      the area under the plot of aerobic count versus storage time was calculated. No
      correlation was found between the total aerobic count of unstored samples and
      bacterial growth during storage, defined as area under growth curves.
      Furthermore, the count of lactic acid bacteria on unstored sausages was often
      below the detection limit. However, the area reflected the extent of
      contamination during processing with bacteria able to grow on cold-stored vacuum
      packed sausages. Storage in a cold storage room was identified as a critical
      point with respect to bacterial recontamination and shelf-life.

PMID- 8251305
TI  - Growth of Staphylococcus aureus in pasta in relation to its water activity.
AB  - Water activity (aw) of pasta decreased linearly with time during drying. A strain
      of Staphylococcus aureus isolated from commercial pasta began multiplying
      immediately after inoculation but decreased in number when aw was reduced to
      below 0.93. Another strain of S. aureus appeared to multiply until the aw was
      below 0.86. The results are discussed in relation to practices for pasta
      production.

PMID- 8251306
TI  - Nurses address the sexual concerns of cancer patients.

PMID- 8251307
TI  - Clinical trials referral resource. Small-cell lung cancer.

PMID- 8251308
TI  - Conformal high-dose radiation plus intraarterial floxuridine for hepatic cancer.
AB  - The role of traditional whole liver irradiation in the treatment of unresectable
      intrahepatic cancers has been limited by low liver tolerance. The development of
      three-dimensional (3D) conformal radiation treatment planning offers the
      potential to treat tumor-bearing portions of the liver to a far higher dose than
      the entire liver could tolerate, while sparing uninvolved liver. This concept
      resembles that used by the surgeon, who determines resectability based on the
      function of the liver anticipated to remain after resection. We have treated
      patients with unresectable intrahepatic cancers by combining 3D conformal
      irradiation with intraarterial hepatic floxuridine, which our laboratory studies
      show is a radiation sensitizer. We have delivered more than 70 Gy to parts of the
      liver without producing significant radiation hepatitis. Furthermore, the median
      survivals of patients with primary hepatobiliary cancer (19 months) and
      colorectal cancer metastatic to the liver (22 months) approach those achieved by
      surgical excision in a more favorable group of patients.

PMID- 8251309
TI  - A review of idarubicin in acute leukemia.
AB  - Since the introduction of the anthracycline idarubicin for the treatment of acute
      myelogenous leukemia, clinicians have questioned whether it offers significant
      benefit over the standard anthracycline, daunorubicin. While the three
      prospectively randomized US trials that compared these two agents in adults with
      newly diagnosed disease differed somewhat, all reported an improved remission
      incidence in patients on the idarubicin arm, and two reported improved survival.
      Overall survival curves, however--albeit better on the idarubicin arm--are still
      depressingly low. Nonetheless, even if the compound represents only an
      incremental improvement, it gives more patients the opportunity for more
      intensive postinduction therapy, such as bone marrow transplantation, or
      innovative approaches to eradicating minimal residual disease, such as the use of
      recombinant interleukin-2. This article describes the mechanism of action and
      pharmacology of idarubicin and reviews the results of clinical studies to date in
      both acute myelogenous leukemia and acute lymphoblastic leukemia.

PMID- 8251310
TI  - Pathogenesis of urinary tract infection--experimental studies of vaginal
      resistance to colonization.
AB  - The review summarizes studies of vaginal colonization resistance against
      Escherichia coli in a primate model. The genital flora surrounding the urethral
      orifice exerts a strong colonization resistance. Amoxicillin profoundly disturbs
      the normal vaginal microflora, reduces its adherence to vaginal epithelial cells
      in vivo and promotes a persistent vaginal E. coli colonization. Certain
      cephalosporins may have a similar effect. The induced ecological changes mimic
      those seen in patients with recurrent urinary tract infections (UTI). Amoxicillin
      also promotes the spread of E. coli from rectum to vagina, which may be of
      clinical significance. Trimethoprim and nitrofurantoin do not have these effects.
      The natural colonization resistance could not clearly be correlated with the
      presence of lactobacilli, which were only transiently reduced by amoxicillin. The
      colonization resistance against E. coli could only partly be restored by vaginal
      instillation of lactobacilli, but was fully restored by flushing of the whole
      vaginal flora from a healthy monkey. Clinical observations suggest that
      accumulation of E. coli around the urethral orifice increases the risk of UTI. We
      conclude that antibiotics and other compounds that interfere with the normal
      genital flora may increase the risk of UTI. This should influence the choice of
      antibiotics in the treatment of UTI.

PMID- 8251311
TI  - In what order should one introduce cyclophosphamide or chlorambucil, cyclosporine
      or levamisole in a child with steroid-dependent frequently relapsing nephrotic
      syndrome?

PMID- 8251312
TI  - Prostacyclin in diarrhoea-associated haemolytic uraemic syndrome.
AB  - The role of prostacyclin (PGI2) in the pathogenesis of haemolytic uraemic
      syndrome (HUS) is controversial. In part, confusion has been caused by failure to
      distinguish between two main sub-types of the syndrome: extrinsic, diarrhoea
      associated HUS (D+ HUS), usually caused by infection with verocytotoxin-producing
      Escherichia coli or Shigella dysenteriae, and the heterogeneous group of non
      prodromal forms where intrinsic factors predominate (D- HUS). This paper
      critically reviews data confined to D+ HUS. Two methods have been used to assess
      PGI2 synthesis; the generation of PGI2 from endothelium in the presence of HUS
      plasma in vitro and the measurement of stable metabolites in body fluids. No
      concensus could be reached with regard to the former. The reported increase of
      PGI2 stable metabolites in plasma may represent reduced clearance or increased
      carriage by plasma lipids. Apparent differences between studies of urinary
      excretion of PGI2 metabolites may reflect the way excretion was expressed. If the
      metabolite concentration is factored for urinary creatinine, it appears that
      renal excretion and thus renal synthesis of PGI2 is reduced. However, these are
      insufficient data on which to attribute the pathogenesis of D+ HUS to disordered
      PGI2 metabolism.

PMID- 8251313
TI  - A syndrome of acute interstitial nephritis and anterior uveitis.
AB  - A syndrome of acute interstitial nephritis (AIN) and anterior uveitis is
      described in two children and the literature is reviewed. These disorders appear
      to improve, in uncontrolled studies, with systemic and topical ophthalmic
      corticosteroid treatment. Although the renal and ocular prognoses appear good, it
      is important to recognize that patients with AIN are at risk for uveitis and if
      present, consultation with an ophthalmologist is recommended.

PMID- 8251315
TI  - Treatment of IgA nephropathy in children: efficacy of alternate-day oral
      prednisone.
AB  - We have previously reported our experience with the use of alternate-day
      prednisone in the treatment of 6 patients with IgA nephropathy who have clinical
      or pathological risk factors for disease progression. We have now treated a total
      of 13 patients and followed them from 4 to 10 years. Patients received an
      alternate-morning dose of prednisone for 2-4 years. Dosage began at 60 mg/m2 for
      3 month, was reduced to 30 mg/m2 by 1 year and 15 mg/m2 by 2 years. At last
      observation, urinary protein excretion was normal in 12 patients and no patient
      had hematuria. Twelve patients had normal estimated glomerular filtration rate
      (GFR) and one had renal insufficiency (GFR = 38 ml/min per 1.73 m2). A renal
      biopsy was performed in 11 patients after 2 years of treatment. Activity score
      decreased from 5.2 to 4.3 (P = 0.03) and chronicity score increased from 2.2 to
      2.8 (P = 0.12). There were no complications of treatment. When compared with a
      historical group, the treated patients had a significant improvement in
      urinalysis (P < 0.00001) and preservation of normal GFR (P = 0.03). We conclude
      that alternate-day prednisone therapy may benefit patients with IgA nephropathy.
      A large prospective controlled trial is needed.

PMID- 8251314
TI  - Serum and urine soluble interleukin-2 receptor in idiopathic nephrotic syndrome.
AB  - Although a cellular immune pathogenesis is suspected in idiopathic nephrotic
      syndrome of childhood (INS), there is scant direct evidence of in vivo immune
      activation. In order to investigate cytokine cascade activation in INS, soluble
      interleukin-2 receptor (sIL-2R) in plasma and urine was characterized and its
      levels measured in INS patients during relapse. Immunochemically detectable sIL
      2R had a molecular mass of 35-46 kDa in both serum and urine and the molecule
      appears to be excreted intact; the pI was 5.05. INS patients had elevated serum
      sIL-2R levels compared with adult normal controls (845 +/- 97 vs. 373 +/- 47
      U/ml, P = 0.001) and were significantly higher than previously published age
      matched controls. Urinary excretion of sIL-2R was 47.2 +/- 13 U/mg creatinine in
      patients. Both the sIL-2R excretion rate and the fractional excretion of sIL-2R
      were positively correlated with the excretion of albumin (P = 0.02 and 0.002,
      respectively). These increased serum and urine levels occurred whether relapse
      was or was not associated with an intercurrent illness. We conclude that: (1)
      despite increased sIL-2R excretion during INS relapse, serum levels are
      significantly elevated; (2) while the elevated urinary levels could result from
      enhanced intrarenal production, they more likely reflect the increased serum
      levels; (3) the elevated sIL-2R levels support an immune pathogenesis in INS.

PMID- 8251316
TI  - Ultrasonographic evaluation of bladder volume in children.
AB  - Although ultrasound has been recently used to estimate bladder volume, several
      different formulae are used. We analysed the accuracy of ultrasound evaluation of
      bladder volume with an ultrasound scanner equipped with a videocassette recorder.
      We determined three dimensions of the bladder, i.e. depth (D), height (H) and
      width (W) by reviewing videotapes in 53 children. D x H x W (DHW) showed a good
      linear relationship with actual bladder volume (r = 0.96). Estimation of bladder
      volume by the regression equation gave errors of 12.5 +/- 8.6% (mean +/- SD) with
      errors above 25% in only 6% of children. Estimation of the volume by simply
      multiplying DHW by a correction factor of 0.80 gave a greater error of 18.9 +/-
      14.0% (P < 0.001) with errors above 25% in 24% of children. Thus, the use of the
      formula volume (ml) = DHW (cm3) x 0.68+4 was sufficiently accurate in the
      ultrasound estimation of bladder volume in children.

PMID- 8251317
TI  - Effects of age at the time of unilateral nephrectomy and dietary protein on long
      term renal function in rats.
AB  - Glomerular filtration rate (GFR) and urinary protein excretion (UpV) were studied
      in male rats with a uninephrectomy at 3 (UNX-3) or 15 weeks of age (UNX-15) and
      fed a low (12%, LP), normal (24%, NP) or high (36%, HP) protein diet.
      Measurements were made every 12 weeks throughout the entire life-span. The UNX
      rats were compared with sham-operated (2K) rats of the same age and on the same
      diets. At 12 weeks after surgery, the GFR of UNX rats, corrected for differences
      in body weight, age and protein intake (GFRcor), ranged between 73% and 77% of
      that of 2K rats. On the HP and NP diet, UpV was higher in UNX-3 than in UNX-15
      rats. On the LP diet, UpV was equally low in both groups. Long-term follow-up
      indicated that the GFR of UNX rats on the HP diet started to decline first,
      followed by those on an NP diet, while those on an LP diet had the longest period
      of stable GFR. For UNX rats, the time to reach a GFRcor of 50% was used as an
      indicator of the length of renal survival. Analysis of variance of the renal
      survival times indicated a highly significant interaction between the protein
      diet and age at the time of UNX. On the HP diet, UNX-3 rats have a shorter renal
      survival time than UNX-15, while on the LP diet UNX-3 rats have a longer renal
      survival time. This indicates that the long-term outcome of UNX at young age
      depends on the protein intake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251318
TI  - Risks of peritoneal membrane failure in children undergoing long-term peritoneal
      dialysis.
AB  - Children undergoing long-term peritoneal dialysis are at risk for membrane
      injury, necessitating conversion to hemodialysis. We analyzed the incidence and
      risk factors for membrane failure (inadequate ultrafiltration with or without
      peritoneal adhesions and decreased peritoneal surface area) in 68 children
      maintained with peritoneal dialysis for more than 3 months at our institution.
      The overall incidence of membrane failure was 16.2% (11/68). Kaplan-Meier
      estimates of peritoneal membrane survival were 88% at 24 months, 72% at 36
      months, 65% at 48 months, and 52% at 60 months. Logistic regression analysis
      demonstrated that the risk of membrane failure increased with the number of
      episodes of peritonitis (odds ratio 1.61). The rate of peritonitis was 1 per 7.02
      patient months in children who developed membrane failure compared with 1 per
      9.18 patient months in children without membrane failures but the rate of
      peritonitis was not predictive of membrane failure (P = 0.09). Multiple logistic
      regression analysis demonstrated that peritonitis caused by Pseudomonas
      aeruginosa or alpha streptococcal organisms were independent predictors of
      membrane failure. We conclude that peritoneal membrane survival declines
      substantially with time on peritoneal dialysis and that membrane failure is
      associated with peritonitis, particularly peritonitis caused by Pseudomonas
      aeruginosa and alpha streptococcal organisms. The mechanism(s) of membrane injury
      are unknown but may be related to the inflammatory response initiated during
      peritonitis.

PMID- 8251319
TI  - Defective antibody response to Hemophilus influenzae type b immunization in
      children receiving peritoneal dialysis.
AB  - Pediatric end-stage renal disease patients, maintained on chronic peritoneal
      dialysis (CPD), may have a variety of immunological abnormalities, including
      hypogammaglobulinemia and poor responses to vaccines. We measured antibody levels
      to Hemophilus influenzae type b (Hib) in 24 CPD patients. Eight children received
      primary Hib immunization while undergoing CPD. Of these, 1 of 8 (12%) lacked
      protective levels of antibody. In another child, who had an initial protective
      response, antibody levels were undetectable 12 months after immunization. Sixteen
      of the patients had not been immunized with Hib vaccine because they were more
      than 5 years old when the vaccine was licensed. In this group, 5 of 16 (31%)
      lacked protective levels of anti-Hib antibody. Of those available for follow-up,
      3 responded normally to Hib vaccine. It is not sufficient to provide childhood
      immunizations to CPD patients with the assumption that those immunizations will
      lead to long-lived immunity. Antibody levels should be measured within a month of
      immunization and at regular intervals thereafter to document immunity.

PMID- 8251320
TI  - Evaluation of delayed puberty in the female adolescent with chronic renal
      failure.
AB  - The purpose of this report is to discuss the differential diagnosis of delayed
      puberty in the adolescent female with chronic renal failure. The appropriate
      therapy varies depending on the etiology of the delay. Frasier syndrome--chronic
      renal failure with true gonadal dysgenesis--should be considered in the diagnosis
      of a normal phenotypic female with end-stage renal disease and delayed puberty.

PMID- 8251321
TI  - Successful treatment with hydrochlorothiazide and amiloride in an infant with
      congenital nephrogenic diabetes insipidus.
AB  - We report a 9-month-old male Latino infant with congenital nephrogenic diabetes
      insipidus (NDI) who presented with hypernatremic dehydration aggravated by severe
      gastroenteritis. Initially, the infant was managed with intravenous fluids
      followed by standard 20 cal/ounce formula and pharmacological therapy, resulting
      in normalization of his serum sodium level. While hydrochlorothiazide therapy
      alone or in combination with prostaglandin inhibitors or amiloride has been
      successful in children and adolescents, this is the first report of the
      successful use of hydrochlorothiazide and amiloride in an infant with congenital
      NDI.

PMID- 8251322
TI  - Swan neck presternal catheter for continuous ambulatory peritoneal dialysis in
      children.
AB  - Since 15 December 1991 four swan neck presternal catheters (SNPC) have been
      implanted in four children aged 2-11 years. The observation period ranged from 4
      to 10 months. The aim of this study was to evaluate the usefulness of a new
      peritoneal dialysis catheter implantation method in paediatric patients. The
      indications for insertion of the SNPC were: young age, use of nappies, obesity
      and recurrent exit site infection (ESI). The surgical technique of the SNPC
      implantation was similar to that used for adults. The chest location of the
      catheter exist site is advantageous for the following reasons: (1) easier care of
      a small child because of greater distance from nappies, (2) better healing and
      decreased risk of ESI in the area with less fat thickness and (3) less trauma. A
      larger number of children with a longer follow-up is necessary for better
      evaluation of the SNPC, as well as for estimation of frequency of ESI and
      peritonitis.

PMID- 8251323
TI  - Hyperlipidemia in childhood nephrotic syndrome.
AB  - Hyperlipidemia is an important characteristic of nephrotic syndrome (NS).
      Elevation of plasma total cholesterol, or more specifically low-density
      lipoprotein cholesterol, is the major lipid abnormality in NS, although
      hypertriglyceridemia may develop as the disorder progresses. The pathophysiology
      of nephrotic hyperlipidemia is complex. The prevailing view is that both hepatic
      synthesis of lipids and of apolipoproteins is increased, and that the clearance
      of chylomicrons and very low-density lipoproteins is reduced. The precise
      contribution of increased lipogenesis and decreased lipid catabolism to
      hyperlipidemia, and their relationship to urinary protein loss, hypoalbuminemia
      and reduced serum oncotic pressure remain controversial. There are two potential
      risks of elevated plasma lipids: atherosclerosis and progression of glomerular
      injury. Although neither of these complications has been proved with certainty,
      there is growing evidence that both may be long-term consequences of NS.
      Therefore, the diagnosis and treatment of lipid abnormalities, important aspects
      of the management of nephrotic children, is summarized here to provide pediatric
      nephrologists with an informed choice.

PMID- 8251324
TI  - New immunosuppressive agents for pediatric transplantation.
AB  - Pediatric transplantation has always been challenging for transplant surgeons.
      Although the higher immunoreactivity and the faster metabolism showed by this
      unique population when compared with adults requires a heavy immunosuppressive
      regimen, the possibility of disrupting the delicate balance of correct
      psychophysical development calls for a regimen of more selective and less toxic
      immunosuppressive drugs. In the past decade several new drugs have been
      investigated and some of them appear to be very promising, although pleiotropic
      toxicities have not yet been eliminated. An appropriate pharmacokinetic approach
      and the evaluation of synergistic multi-drug combinations by rigorous
      mathematical models would lead to highly selective immunosuppressive regimens
      which may result in virtually no toxicity.

PMID- 8251326
TI  - A transplant of real life.
AB  - A case of steroid-resistant nephrotic syndrome with focal segmental
      glomerulosclerosis leading to renal failure in a 4-year-old girl is described by
      her mother, with special emphasis on the problems resulting from recurrence of
      this disease, with graft loss in three successive kidney transplants. This report
      chronicles the gradual evolution from a family's initial heavy dependence upon
      medical solutions to their ultimate primary emphasis upon spiritual values, with
      medicine seen as the support toward achieving the child's psychological well
      being and spiritual growth. The physician's role in balancing medical decision
      making, non-medical alternatives, and demands on limited and precious resources
      in such difficult cases is discussed.

PMID- 8251325
TI  - Renal amino acid transport: cellular and molecular events from clearance studies
      to frog eggs.
AB  - This article reviews recent advances in the mechanisms of renal amino acid
      transport. Renal amino acid transport is necessary to efficiently reclaim
      approximately 450 mmol amino acids from the glomerular ultrafiltrate each day in
      man. In general, individual amino acids are transported across the epithelial
      membrane of the proximal tubule by a sodium (Na+) dependent mechanism. This
      cotransport process utilizes the energy of the Na+ gradient to enter the cell.
      The amino acid then exits the basolateral surface and Na+ is pumped out by the
      Na(+)-K(+)-ATPase located in the basolateral membrane. In addition to the
      cellular accumulation of amino acids across the luminal membrane, these compounds
      may be taken up by the cell from the basolateral surface. Most amino acids are
      transported both individually and in a series of seven group specific processes.
      Human disorders of amino acid transport have been described for six of the seven
      transport systems. The process of ontogeny of amino acid accumulation by the
      proximal tubule is a complex one and will be further discussed in this review. A
      number of factors including pH, ion dependency, electrogenicity of transport
      process, as well as a variety of hormonal factors, may contribute to the
      regulation of amino acid transport. Gene expression of several amino acid
      transporters has been successfully performed using the oocyte of the frog Xenopus
      laevis. Using this system, a number of transporters have been cloned. Such a
      strategy will permit the cloning of virtually all transporter molecules, and thus
      we can anticipate the elucidation of the structure of the transporters. However,
      for a comprehensive understanding of cytoskeletal interactions protein
      phosphorylation and phospholipid domains and their linkage to the primary
      structure of the transporter need to be studied. The future for research in this
      area is indeed a bright one.

PMID- 8251327
TI  - Clinical quiz. Congenital coarctation of the aorta.

PMID- 8251328
TI  - Extent of urinary tract involvement and imaging in childhood urinary tract
      infections.

PMID- 8251329
TI  - Acute poststreptococcal glomerulonephritis followed by acute rheumatic carditis:
      an unusual case.

PMID- 8251330
TI  - Kawasaki disease and acute renal failure.

PMID- 8251331
TI  - Regulation of cell surface polarity in renal epithelia.
AB  - In the kidney, polarized epithelial cells play critical roles in ion, fluid and
      solute reabsorption from the ultrafiltrate to the blood supply. Detailed analysis
      of protein distributions has revealed that ion channels, transporters and pumps
      are restricted to distinct domains of the plasma membrane that face either the
      ultrafiltrate (apical membrane) or the blood supply (basal-lateral membrane). The
      importance of the development and maintenance of the polarized distributions of
      these proteins in renal epithelia for normal cell function is demonstrated by the
      fact that several disease states are characterized by abnormal distributions of
      proteins; for example in polycystic kidney disease, Na+/K(+)-ATPase has been
      detected in the apical and lateral membranes, compared with normal cells where
      Na+/K(+)-ATPase is localized in the basal-lateral membrane domain. Recent studies
      indicate that the development of restricted distributions of proteins at the cell
      surface of Madin Darby canine kidney epithelial cells is determined by direct
      sorting of proteins in the trans Golgi network into vesicles that are delivered
      vectorially to either the apical or basal-lateral membrane. Upon arrival at the
      plasma membrane, some proteins, such as Na+/K(+)-ATPase, may be selectively
      retained by binding to the membrane cytoskeleton.

PMID- 8251332
TI  - Genetically engineered kidneys.
AB  - We review the available methods of creating genetically engineered kidneys. These
      include transgenic technology to introduce novel genes or delete existing genes
      and methods of gene transfer into the post-natal or adult kidney. The use of such
      technology has provided insights into renal development and growth and created
      new animal models of human diseases. Although some of these techniques are of
      potential use for introducing therapeutically useful gene products into the
      diseased kidney, many problems remain to be solved before this aim is attained.

PMID- 8251333
TI  - Cell death programmed in uninduced metanephric mesenchymal cells.
AB  - Metanephric mesenchyme may be converted to epithelia by the uteric bud (in vivo)
      and the spinal cord (in vitro). In their absence, the uniduced cells die or
      disappear. Morphological data, both in vitro and vivo, suggest that the demise of
      these cells is brought about by apoptosis, programmed cell death. By measuring
      DNA fragmentation in induced and uniduced cells, this study confirms not only
      that apoptosis occurs in the absence of an inducer, but also suggests that rescue
      from this process may be an important step in kidney development.

PMID- 8251334
TI  - Expression of the epidermal growth factor receptor in fetal kidney.
AB  - Formation of the human kidney begins at the 6th week of fetal life when the first
      generations of nephrons are generated from foci of metanephric mesenchyme through
      contact with the branches of the ureteric bud. This process requires a
      proliferative burst which must be tightly regulated by local signals. In this
      report, we review the evidence that the epidermal growth factor receptor molecule
      is an important arbiter of these events.

PMID- 8251335
TI  - Growth factors and kidney development.
AB  - The formation of the metanephric kidney is dependent upon the timed and
      sequential expression of a number of polypeptide growth factors. To shed light on
      the participation of members of the insulin-like growth factor (IGF) and
      epidermal growth factor/transforming growth factor-alpha (EGF/TF-alpha) families,
      we measured the synthesis of IGF-I, IGF-II, EGF and TGF-alpha by developing rat
      metanephroi in organ culture and determined the effect of anti-growth factor
      antibodies on growth and development. IGF-I, IGF-II and TGF-alpha were produced
      by metanephroi and released into culture media. We could detect no EGF. Inclusion
      of anti-IGF-I, anti-IGF-II, anti-IGF-II receptor or anti-TGF-alpha antibodies in
      organ cultures inhibited growth and development of metanephroi. Our findings
      suggest that both members of the IGF family and TGF-alpha are produced within the
      developing metanephros and promote renal organogenesis.

PMID- 8251336
TI  - The role of protein phosphorylation in renal amino acid transport.
AB  - Changes in tubular reabsorption of amino acids and other solutes are
      characteristic of the immature renal tubule and of various hereditary
      nephropathies. The cellular mechanisms governing these aberrations in renal amino
      acid transport have not been established. Calcium (Ca2+)-dependent protein
      kinases are known to phosphorylate membrane-bound carrier proteins, thereby
      modulating transport of various solutes by the proximal tubule. The role of these
      enzymes in regulating renal tubular amino acid transport, particularly during
      kidney development, is unknown. We investigated: (1) the effect of Ca(2+)- and
      phospholipid-dependent protein kinase [protein kinase C (PKC)] and
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) on sodium chloride (NaCl)
      linked proline transport by renal brush border membrane vesicles (BBMV) from
      adult rats using the "hypoosmotic shock" technique (lysis of vesicles); (2) the
      activity, expression and subcellular distribution (cytosol, particulate, BBM) of
      Ca(2+)-dependent protein kinases in kidneys from 7-day-old and adult rats using
      MBP 4-14 and autocamtide II phosphorylation assays for PKC and CaMKII,
      respectively, endogenous protein phosphorylation (using gel electrophoresis and
      autoradiography) and Western immunoblot analysis to detect PKC and CaMKII. The
      studies showed: (1) endogenous (membrane-bound) CaMKII and PKC as well as
      exogenous, highly purified PKC inhibit proline uptake by phosphorylated,
      lyzed/resealed BBMV when compared with control vesicles; the voltage-clamped,
      nonelectrogenic component of proline transport was inhibited by PKC- but not
      CaMKII-mediated phosphorylation; (2) a Ca(2+)-dependent activity of both kinases
      was evident in all subcellular fractions tested in immature and adult
      kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251337
TI  - Regulation of Na+,K(+)-ATPase gene expression: a model to study terminal
      differentiation.
AB  - This review focuses on the ontogeny of factors involved in the transcriptional
      regulation of Na+,K(+)-ATPase expression. The Na+,K(+)-ATPase enzyme is of vital
      importance for cell function. It is likely that the limited availability of
      Na+,K(+)-ATPase in infant tissue is the major limiting factor for adaptation to
      extra-uterine life in several organs. The factors regulating Na+,K(+)-ATPase gene
      transcription in infancy are discussed. Special emphasis is given to the role of
      circulating hormones such as glucocorticoids and thyroxine.

PMID- 8251338
TI  - Ontogeny of renin and AT1 receptor in the rat.
AB  - The enzyme renin and the angiotensin II (Ang II), subtype I receptor (ATI) are
      developmentally regulated in a tissue-specific manner. In early life, renin is
      expressed widely along the renal vasculature. As maturation progresses, there is
      a decrease in renin mRNA levels and a shift in the localization of renin close to
      the glomerulus. In addition, in the newborn rat, the number of renin-secreting
      cells is higher than in the adult rat. Exposure of neonatal and adult cells to
      Ang II results in a decrease of similar magnitude in the number of renin
      secreting cells. These findings suggest that the high levels of renin observed in
      immature animals are due to increased renin synthesis and release rather than to
      a blunted response to Ang II. Expression of the ATI gene is also developmentally
      regulated in a tissue-specific manner. With maturation, ATI mRNA levels decrease
      in the kidney while they increase in the liver. The localization of ATI
      transcripts in precursor cells of the nephrogenic cortex suggests a role for this
      receptor in nephron growth and development. Inhibition of ATI with DUP753 results
      in delayed kidney and somatic growth and in increased renin mRNA levels and
      recruitment of renin-containing cells. These observations suggest that Ang II
      exerts a tonic negative feedback on renin gene expression via the ATI receptor
      subtype. Further studies are necessary to delineate the molecular and cellular
      signals mediating these developmental changes.

PMID- 8251339
TI  - Expression of the human renin gene in transgenic mice throughout ontogeny.
AB  - Expression of a human renin genomic DNA clone extending 900 base pairs upstream
      and 400 base pairs downstream of the gene has been previously examined in adult
      transgenic mice. In adults, expression of human renin was evident in kidney,
      reproductive tissues, adrenal gland and lung. Previous studies of mouse and rat
      renin have demonstrated that kidney renin becomes evident at approximately 15
      days of gestation and that expression is localized first to smooth muscle cells
      of the developing renal arterial tree and becomes progressively restricted to
      juxtaglomerular cells. As a prelude to performing cell specificity studies to
      elucidate the pattern of human renin gene expression in the developing kidney,
      15.5 and 17.5 days of gestation fetuses and newborns were obtained for expression
      analysis. Tissues were pooled and expression was examined in kidney, liver,
      gastrointestinal (GI) tract, lung, heart and brain. The number of transgenic
      fetuses in each pool was determined by human renin-specific polymerase chain
      reaction of DNA purified from placenta or tail biopsies. Renal human renin
      expression was abundant at all three time points. Expression was also evident in
      the GI tract at 15.5 and 17.5 days of gestation. Interestingly, although no human
      renin mRNA was evident in lung at 15.5 or 17.5 days of gestation, extremely high
      levels of human renin mRNA were detected in the newborn lung. Expression of the
      human renin gene in these tissues was further confirmed by differential primer
      extension analysis which is capable of differentiating the closely related human
      and mouse renin messages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251341
TI  - Atrial natriuretic peptide in renal development.
AB  - Although discovered little more than a decade ago, atrial natriuretic peptide
      (ANP) has been shown to play a significant role in the maintenance of sodium
      homeostasis. Immediately after birth, plasma ANP concentration is very high
      concurrent with right atrial dilatation and a high urinary excretion of cyclic
      GMP (cGMP), the second messenger for ANP. Following postnatal diuresis and
      natriuresis, atrial volume, plasma ANP concentration, and urinary cGMP excretion
      decrease to baseline levels. In the ensuing suckling period, the diuretic and
      natriuretic response to acute saline volume expansion are attenuated, an effect
      which is offset by the lower hematocrit at this age. Increase in hematocrit by
      isovolemic exchange transfusion results in a greater rise of plasma ANP
      concentration following volume expansion, but a reduced excretion of cGMP.
      Intravenous infusion of ANP results in greater plasma ANP concentration, and
      greater urinary excretion of cGMP and sodium, in adult than in young rats. This
      increased metabolic clearance of ANP during early development is due at least in
      part to increased activity of clearance receptors. In addition, neutral
      endopeptidase contributes to removal of circulating ANP in maturing as well as
      adult rats. Infusion of ANP in neonatal or adult rats results in accumulation of
      cGMP in glomerular podocytes, with a higher threshold for activation in immature
      animals. Despite the similar response of intracellular generation of cGMP
      following exposure to ANP in neonatal and adult rats, egression of ANP out of
      glomeruli is low in neonates, an effect that is due to immaturity of an organic
      acid transporter.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251340
TI  - Molecular aspects of kallikrein and kininogen in the maturing kidney.
AB  - Kinins are vasoactive paracrine peptides which participate in a wide range of
      functions, including the regulation of local organ blood flow, systemic blood
      pressure, transepithelial water and electrolyte transport, cellular growth,
      capillary permeability and inflammatory response, and pain. The recent
      introduction of specific bradykinin receptor subtype antagonists has greatly
      advanced our understanding of the role of the kallikrein-kinin system (KKS) in
      various physiological and disease states. However, a major gap remains in our
      knowledge of the role of kinins in early development. In this review, evidence is
      presented that the developing nephron expresses both tissue kallikrein and
      kininogen, and that the genes encoding the components of the KKS are subject to
      considerable developmental regulation. The activity of the intrarenal kinin
      generating system is lowest in the developing kidney and increases with age.
      Completion of nephrogenesis is characterized by a marked surge in intrarenal
      kallikrein synthesis and gene transcription. Maturation is associated with
      redistribution of intrarenal kallikrein and its messenger RNA from the inner to
      outer cortical nephrons following the centrifugal pattern of nephron development.
      Challenges for the future include delineation of the direct role of kinins in the
      maturation of renal functions and elucidation of the molecular mechanisms
      underlying the developmental expression of the KKS.

PMID- 8251342
TI  - Influence of renal nerves on renal function during development.
AB  - The present review summarizes recent studies describing the role of renal
      sympathetic innervation in the regulation of renal function during development.
      The afferent renal innervation appears early during fetal life and probably
      precedes the development of efferent renal nerves. There is suggestive evidence
      that renal nerves are required for the proper development of the kidney and that
      neurotrophic growth factors play an important role in renal embryogenesis and in
      renal tubular differentiation. Renal sympathetic innervation modulates renal
      hemodynamics early during development. Renal nerve stimulation during alpha
      adrenoceptor blockade produces renal vasodilation in fetal and newborn animals
      but not in adults. Unlike the effect of renal nerves on fetal renal hemodynamics
      which is observed in the young fetus, the role of renal sympathetic nerves in
      modulating fluid and electrolyte homeostasis seems to develop during late
      gestation. Recent studies have also shown that renal nerves play an important
      role in regulating renin secretion during the transition from fetal to newborn
      life. For example, renal denervation during fetal life suppressed the
      physiological rise in plasma renin activity associated with delivery and
      decreased renal renin mRNA levels after birth. Taken together, these studies
      suggest that renal nerves influence fetal renal development and that the
      influence of renal sympathetic innervation on renal hemodynamics and function
      changes with maturation.

PMID- 8251343
TI  - The effect of vasopressin on the cytoskeleton of the epithelial cell.
AB  - Vasopressin (AVP) promotes the fusion of vesicles containing water channels with
      the apical membrane of receptor cells in the amphibian bladder and mammalian
      kidney. Fusion is accompanied by depolymerization of the actin cytoskeleton. In
      this review, we present the evidence for actin depolymerization by AVP in the
      whole cell, and the application of confocal microscopy and immunogold electron
      microscopy in localizing depolymerization to the apical region of the receptor
      cell.

PMID- 8251344
TI  - Nephrogenic diabetes insipidus: identification of the genetic defect.
AB  - Congenital nephrogenic diabetes insipidus (NDI) is an X-linked inherited disorder
      characterized by renal resistance to the antidiuretic hormonal action of arginine
      vasopressin. The disease gene has been assigned to the subtelomeric region of the
      X chromosome long arm by demonstrating close linkage between NDI and several X
      chromosomal DNA markers. The finding of closely linked genetic markers is useful
      in the diagnosis of NDI. Receptor studies in patients have indicated that NDI
      might be due to the absence or an abnormality of the adenylate cyclase-bound
      vasopressin type 2 receptor. This assumption was supported by the discovery of
      functional vasopressin V2 receptor activity in somatic cell hybrid cell lines
      that carried at least the distal part of the human X chromosome long arm.
      Definite evidence for a V2 receptor defect being the cause of NDI was found in a
      recent study demonstrating point mutations in the V2 receptor gene from affected
      individuals. Direct mutation analysis is now applicable for accurate carrier
      detection and early (prenatal) diagnosis.

PMID- 8251346
TI  - Dapsone: modes of action, toxicity and possible strategies for increasing patient
      tolerance.
AB  - Dapsone is useful in the treatment of a number of inflammatory conditions which
      are characterized by neutrophil infiltration. It is the drug of choice for
      suppression of the symptoms of dermatitis herpetiformis, as it inhibits the
      process by which neutrophils leave the circulation and migrate to lesional sites.
      It also prevents the tissue destruction normally caused by the neutrophils'
      respiratory burst. Although dapsone can cause a number of serious idiosyncratic
      reactions, such as agranulocytosis, tolerance of the drug at higher doses is more
      usually determined by its haematological side-effects of methaemoglobinaemia and
      haemolysis. These effects are due entirely to the hepatic N-hydroxylation of
      dapsone to a hydroxylamine metabolite, some of which escapes from the liver and
      rapidly enters red cells. Attempts have been made to counteract the haemotoxic
      effects of the metabolite by the use of antioxidants such as vitamins E and C.
      Recently, the co-administration of a metabolic inhibitor such as cimetidine has
      been shown to reduce significantly dapsone-dependent methaemoglobinaemia, without
      any change in drug efficacy. It remains to be seen if this approach will be
      adopted clinically, to improve patient tolerance of high dapsone dosage.

PMID- 8251345
TI  - Maintenance of cell volume in the central nervous system.
AB  - Maintenance of the ionic and osmotic composition and volume of intra- and
      extracellular fluids in the brain is crucial for normal functioning of the
      central nervous system (CNS). Osmoregulation in the CNS is mediated by solute and
      water transport across the blood-brain barrier, choroid plexus and 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 CNS osmotic and ionic balance is maintained. In
      this review, I will discuss our current understanding of cell volume regulation
      in the CNS and how it relates to various disease processes, such as hyponatremia,
      renal failure and hypernatremia. 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- 8251347
TI  - Restricted T-cell receptor V beta gene usage in the skin of patients with guttate
      and chronic plaque psoriasis.
AB  - A strong association between acute guttate psoriasis and group A, beta-haemolytic
      streptococcal infections is well established. Furthermore, streptococcal M
      proteins and toxins have been shown to act as superantigens, stimulating
      subpopulations of T lymphocytes expressing particular V beta families. We have
      therefore studied the possible role of streptococcal superantigens in psoriasis
      by staining peripheral T lymphocytes and skin sections from patients with guttate
      or chronic plaque psoriasis for the expression of nine TCR V beta families, using
      a range of monoclonal antibodies. A marked over-representation of V beta 2+ T
      lymphocytes was observed in the dermis and epidermis of patients in both groups,
      when compared with T lymphocytes in their peripheral blood. A less marked dermal
      increase in V beta 5.1+ T lymphocytes was also observed in these patients. These
      findings are consistent with the involvement of a superantigen, possibly
      streptococcal, in the pathogenesis of psoriasis.

PMID- 8251348
TI  - The carriage of Malassezia furfur serovars A, B and C in patients with pityriasis
      versicolor, seborrhoeic dermatitis and controls.
AB  - The aetiological role of Malassezia furfur in various dermatoses is
      controversial. The role of the three serovars of M. furfur in Malassezia
      associated diseases has not been investigated. This study measured population
      densities of M. furfur serovars A, B and C, propionibacteria and Micrococcaceae
      on the chest, back, forehead, left and right cheeks of 10 patients with
      pityriasis versicolor, and 10 age- and sex-matched controls; and 10 patients with
      seborrhoeic dermatitis, and 10 age- and sex-matched controls. The population
      densities of M. furfur, propionibacteria and Micrococcaceae did not vary at a
      given site between patients and the corresponding control subjects. Malassezia
      furfur serovar A was found to be the predominant isolate on the chest and back of
      all four groups, but there was no difference in the distribution of serovars on
      the forehead and cheeks. No serovar was specifically associated with lesional
      skin in either disease. Thus, this data indicated that there was no difference in
      either the total population density of M. furfur or the distribution of serovars
      on lesional skin compared with control skin in either pityriasis versicolor or
      seborrhoeic dermatitis.

PMID- 8251349
TI  - Merkel cells in human fetal eccrine glands.
AB  - The presence of human Merkel cells in the eccrine ridges and eccrine germs was
      studied, using antibodies to simple epithelial keratins, in separated epidermal
      sheets with attached eccrine ducts. The localization of Merkel cells could be
      analysed three-dimensionally in the wet, whole-mount of the stained sheets. In
      the plantar skin of a 12-week-old human fetus, immunoreactive (ir-) Merkel cells
      were randomly located in the flattened epidermis. In the plantar skin of a 15
      week-old human fetus, there was early development of eccrine germs, and Merkel
      cells were concentrated in eccrine gland ridges. In the plantar skin of a 20-week
      old human fetus, eccrine germs were well formed and ir-Merkel cells were located
      within the developing eccrine ridges and ducts. In the plantar skin of adults,
      the eccrine concentration of Merkel cells was markedly reduced. Concentration of
      Merkel cells on the eccrine structures was also observed in the scalp skin of
      human fetuses. This tendency continued into adult life, although there was a
      marked reduction in the total number of Merkel cells. These findings suggest that
      epidermal Merkel cells move down into the eccrine ducts as eccrine germs extend
      into the mesenchyme. Alternatively, they may develop de novo from the
      keratinocytes of the eccrine duct. In view of the expression of nerve growth
      factor receptor in fetal Merkel cells, it is postulated that these eccrine gland
      Merkel cells play a role in the formation of the periglandular nerve plexus.

PMID- 8251350
TI  - Barrier function parameters in various keratinization disorders: transepidermal
      water loss and vascular response to hexyl nicotinate.
AB  - In this study, we characterized the stratum corneum barrier function in 39
      patients with various keratinization disorders (autosomal dominant ichthyosis
      vulgaris [ADI] [n = 7], X-linked recessive ichthyosis [XRI] [n = 6], autosomal
      recessive congenital ichthyosis [CI] [n = 10], dyskeratosis follicularis
      [Darier's disease; DD] [n = 8], erythrokeratoderma variabilis [EKV] [n = 8]), and
      21 healthy volunteers, using two non-invasive methods: transepidermal water loss
      (TEWL) measuring outward transport of water through the skin by evaporimetry, and
      the vascular response to hexyl nicotinate (HN) penetration into the skin as
      determined by laser-Doppler flowmetry. Significantly increased TEWL values were
      found on the volar forearm in all three forms of ichthyosis, compared with the
      healthy control group, with the highest TEWL values in the CI group. The
      penetration of HN on the volar forearm was accelerated in patients with ADI, XRI
      and CI, as indicated by a shorter lag time (t0) between HN application and
      initial vascular response. However, differentiation between CI and the other
      ichthyoses was not possible by this method. When using both methods in DD and
      EKV, no differences compared with the healthy controls could be detected on the
      volar forearm, where the skin was principally unaffected; only the measurements
      from the affected skin on alternative sites demonstrated significantly increased
      TEWL values. In ADI and CI, however, normal-appearing skin also showed impaired
      values. We conclude that both TEWL and the vascular response to penetration of HN
      are suitable methods to monitor the skin barrier function in keratinization
      disorders, and are helpful in discriminating between these disorders.

PMID- 8251352
TI  - A model of measured percussive mechanical trauma and its effects on skin.
AB  - In this study, the role of mechanical trauma to skin in industrial dermatitis is
      considered. The percussive component of mechanical trauma to skin is investigated
      by modelling it, using an oscillating device which can supply a range of
      percussive trauma doses. The instrument is electronically controlled, and
      contains sensors which monitor the force and displacement throughout each impact.
      From this information, a value proportional to the dose delivered to the skin is
      calculated and used, rather than the driving power of the percussor. The rate of
      dose is also controlled. In this study, doses were delivered at a frequency of 7
      Hz. Eight volunteers were given regimens of percussive trauma at regular
      intervals over a 5-day period. Half the group received a dose of 4 mJ/cm2 per
      impact, the other half received double this dose. The skin response was evaluated
      using non-invasive measurements of transepidermal water loss, skin thickness, and
      erythema. The results demonstrate that erythema, skin thickness and
      transepidermal water loss are all increased after mechanical challenge--erythema
      and water loss by amounts dependent upon the trauma dose applied. The
      transepidermal water loss results indicate that for the subjects used in our
      study, there was a trauma threshold reached after a cumulative dose of greater
      than 250 J/cm2.

PMID- 8251351
TI  - Skin barrier function and dermal inflammation. An experimental study of
      transepidermal water loss after dermal tuberculin injection compared with SLS
      patch testing.
AB  - The reaction of the skin water barrier to dermal inflammation was studied in 15
      healthy volunteers. Dermal inflammation was induced either by injection of
      tuberculin (Mantoux test) or by a 24-h sodium lauryl sulphate (SLS) patch test on
      the volar forearm. Measurement of transepidermal water loss (TEWL) was used for
      evaluation of the skin barrier function. Inflammation was quantified by
      assessment of blood flow by laser-Doppler flowmetry. Measurement from uninvolved
      skin in the test region > 7 cm distant from the test sites served as control.
      Measurements were performed twice, separated by an interval of 6 days. Throughout
      the study, TEWL values were higher in the SLS test sites than in the Mantoux
      reactions, although the blood flow was significantly increased in Mantoux
      reactions compared with SLS test sites. This indicates that the impaired skin
      barrier function caused by SLS is due to a direct cytotoxic effect, and cannot be
      explained by the inflammatory response alone. At control sites, blood flow and
      TEWL were significantly higher on the arm with the Mantoux test than the arm with
      the SLS patch test. The significant inflammation caused by the Mantoux reaction
      may cause functional alterations in the clinically normal skin > 7 cm distant
      from the test area.

PMID- 8251353
TI  - The effect of zinc in the form of erythromycin-zinc complex (Zineryt lotion) and
      zinc acetate on metallothionein expression and distribution in hamster skin.
AB  - The occurrence of zinc-induced synthesis of metallothionein in skin after topical
      application of the anti-acne drug Zineryt lotion was investigated in hamster
      ears. The dinitrophenyl hapten-sandwich immunohistochemical method involving a
      monoclonal anti-metallothionein (MT) antibody (E9) was used to detect and
      localize zinc-binding MT in the 'treated' and untreated hamster skin. Atomic
      absorption spectrophotometry and dithizone histochemistry indicated that zinc
      penetrated the skin more readily, and accumulated more efficiently within the
      sebaceous glands, when applied to the skin surface as the organo-zinc complex,
      rather than as the inorganic zinc salt. MT and zinc had similar distributions in
      hamster skin exposed to the metal. Thus, MT immunoreactivity was especially
      intense in the sebaceous glands of Zineryt lotion-treated skin, with evidence of
      nuclear distribution in some cells. Zinc delivered to the sebaceous glands, and
      released from the organo-complex under the prevailing aqueous conditions,
      certainly induced MT synthesis; the cysteine-rich protein may protect the
      pilosebaceous units during the inflammatory phase of acne by scavenging generated
      oxyradical species.

PMID- 8251354
TI  - In dermographic urticaria H2 receptor antagonists have a small but
      therapeutically irrelevant additional effect compared with H1 antagonists alone.
AB  - Two studies of the additional effect of an H2 receptor antagonist when given in
      combination with an H1 antagonist were undertaken in dermographic urticaria.
      Using a randomized, double-blind, crossover design in 19 patients, a combination
      of cetirizine (10 mg at night) and ranitidine (150 mg twice daily) was compared
      with a combination of cetirizine (10 mg at night) and placebo. The addition of
      ranitidine did not produce any significant difference in linear analogue scores
      for weal, itch or sleep disturbance. There was a significant depression of the
      frictional force/wealing response curve with an increase in wealing threshold (P
      < 0.0001) following the addition of H2 blockade. The wealing threshold was 54.7
      +/- 4.4 (mean +/- SEM) g/mm2 for the H1 antagonist alone, and 73.2 +/- 5.7 for
      the combination of H1 and H2 antagonists. In a second similar study involving
      nine different patients, comparing terfenadine (120 mg twice daily) with a
      combination of terfenadine and ranitidine (150 mg twice daily), the weal
      threshold was 59.8 +/- 6.6 for the H1 antagonist alone, and 73.0 +/- 6.4 for the
      combination of H1 and H2 antagonists. Thus, in dermographic urticaria, adding an
      H2 antagonist to treatment with a potent H1 antagonist gives a small, significant
      reduction in wealing response, but no symptomatic benefit. We conclude that
      involvement of the H2 receptor in this urticarial disease is minimal, and does
      not justify the use of H2 receptor antagonists.

PMID- 8251355
TI  - The effect of cetirizine on symptoms and wealing in dermographic urticaria.
AB  - The effect of cetirizine, 10 mg at night, on dermographic urticaria, was studied
      in 19 patients. The study design was a randomized, double-blind, crossover
      comparison with placebo, each treatment being given for 7 days. Patients kept a
      daily diary of itch and weal severity (100-mm linear analogue scale), and
      recorded sleep disturbance. The dermographic weal response was measured
      objectively with a spring-loaded stylus, and the weal threshold calculated from
      the force/response curve. There was a small, insignificant subjective response to
      placebo, but no objective response. On cetirizine, the subjective assessment of
      wealing was reduced from 34.3 +/- 6.7 (mean +/- SEM, 0-100 scale) to 16.8 +/- 4.1
      (P = 0.02), itch was reduced from 43.2 +/- 6.6 to 19.4 +/- 4.1 (P = 0.001), and
      nights disturbed from 46.2 to 8.8% (P = 0.03). There was a shift to the right in
      the position of the force/response curve, and the wealing threshold increased
      from 24.6 +/- 3.2 to 54.7 +/- 4.4 g/mm2 (P = 0.00001), but there was no
      correlation between change in itch scores and wealing threshold. Cetirizine 10 mg
      daily is an effective treatment in dermographic urticaria, and its usefulness
      will depend on the prevalence of unwanted effects.

PMID- 8251356
TI  - A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim
      in severe psoriasis.
AB  - An open, 12-week, multicentre study was conducted to assess the efficacy of
      piritrexim isethionate in the treatment of severe psoriasis. Piritrexim
      isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot
      form polyglutamates, and may be as effective as methotrexate in the treatment of
      psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates
      are responsible for the hepatotoxicity of methotrexate, piritrexim should be less
      hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five
      patients were enrolled, of whom 41 completed the study. Patients were allocated
      to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses
      over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg
      groups). Twenty-four of the 41 patients who completed the study had a greater
      than 50% improvement in the severity of their psoriasis, as demonstrated by a
      reduction in the Psoriasis Severity Score, a measure analogous to the PASI
      scoring system. Adverse events were common, but mild, and were controlled by dose
      reduction. Piritrexim appears to be an effective therapy for severe psoriasis at
      doses of 300 and 450 mg weekly, in three divided doses over 36 h.

PMID- 8251357
TI  - The therapeutic effect of intralesional interferon in classical Kaposi's sarcoma.
AB  - Interferon alpha-2a, which has antineoplastic, antiviral, immunomodulatory, and
      antiangiogenic effects, was evaluated in a prospective study, treating 10 lesions
      of patients with classical Kaposi's sarcoma. Ten patients received injections of
      interferon alpha-2a intralesionally in a dose of 3 million units three times
      weekly for 4 weeks, and in a variable dose for 4 more weeks. Two of the patients
      had a complete response, and in one of these, distant lesions also responded.
      Seven had a partial response, and one did not respond. The treatment was
      generally well tolerated. The results of our study support the use of interferon
      in the therapy of classical Kaposi's sarcoma, although it would appear that to
      achieve maximum efficacy, a longer period of treatment is needed.

PMID- 8251358
TI  - An historical note on pyoderma faciale.
AB  - Pyoderma faciale is a rare disorder, recently interpreted as a maximal variant of
      rosacea in women, with a sudden onset. A survey of the history of pyoderma
      faciale is presented.

PMID- 8251359
TI  - Paroxysmal pruritus and multiple sclerosis.
AB  - We report a patient who presented with paroxysmal pruritus in association with
      multiple sclerosis. Magnetic resonance imaging of the cervical spinal cord showed
      a lesion at a level corresponding to the dermatomal location of the pruritus.

PMID- 8251360
TI  - Annular vasculitis associated with pregnancy.
AB  - A 29-year-old woman presented in the 31st week of pregnancy with an unusual
      bilateral, erythematous eruption on the posterior calves, which clinically
      resembled erythema annulare centrifugum. A biopsy showed features of a mild
      leucocytoclastic vasculitis. Within 2 days of delivery the rash had almost
      resolved, suggesting that its activity was related to the pregnancy. The
      diagnosis is consistent with 'annular vasculitis', which we suggest represents a
      distinct variant of leucocytoclastic vasculitis, and a distinct
      clinicopathological entity. We are not aware of any previous reports of an
      association between annular vasculitis and pregnancy.

PMID- 8251361
TI  - A scleroderma-like variant of recessive dystrophic epidermolysis bullosa?
AB  - We report a 17-year-old Japanese girl with typical clinical features of recessive
      dystrophic epidermolysis bullosa (RDEB). She had initially been diagnosed as
      suffering from systemic sclerosis because her skin became sclerotic at the age of
      21 months, and there was no apparent blister formation. She subsequently
      developed severe dystrophic skin changes. However, there was histological
      evidence of subepidermal cleavage, diminished basement membrane zone
      immunohistochemical reactivity to anti-type VII collagen monoclonal antibody, and
      markedly decreased numbers of anchoring fibrils on electron microscopy. Although
      both the clinical and laboratory findings support a diagnosis of RDEB, we cannot
      exclude the possibility that our patient might represent a new clinical entity.

PMID- 8251362
TI  - Folded skin with an underlying cutaneous smooth muscle hamartoma.
AB  - We report a 3-month-old male infant with marked folding of the skin, who
      manifested mental retardation and delayed growth at the age of 31 months.
      Histological examination of the folded skin disclosed smooth muscle hamartomatous
      changes. To our knowledge, this represents the third reported case of folded skin
      with an underlying smooth muscle hamartoma.

PMID- 8251363
TI  - Amelanotic malignant melanoma presenting as malignant schwannoma.
AB  - A 78-year-old woman presented with a 14-month history of a nodule on the sole of
      her left foot. It had been increasing in size, and had become ulcerated.
      Histological, immunochemical and ultrastructural studies of the primary tumour
      revealed melanocytic and Schwannian characteristics, and posed diagnostic
      difficulties. The final diagnosis of a malignant melanoma with Schwannian
      differentiation was established on the basis of the clinical course, with the
      development of metastases in the subcutis, lymph nodes, liver and brain, as well
      as a shift in differentiation of the metastases towards cells containing giant
      melanosomes, typical of melanoma.

PMID- 8251364
TI  - Fanconi's anaemia associated with multicentric Bowen's disease and decreased NK
      cytotoxicity.
AB  - We report a patient with Fanconi's anaemia and multiple lesions of vulvo-anal
      Bowen's disease. She was thrombocytopenic and lymphopenic, and NK-mediated
      cytotoxicity was undetectable. The vulvar lesions did not contain papillomavirus
      DNA. In vitro studies showed a possible benefit from acitretin treatment on bone
      marrow stem cells. However, low-dose acitretin given for 14 months did not
      prevent the development of an anal squamous carcinoma. Acitretin therapy was,
      however, associated with a sustained rise in the platelet count.

PMID- 8251365
TI  - The clinical spectrum of lipoatrophic panniculitis encompasses connective tissue
      panniculitis.
AB  - Two patients with widespread, chronic, relapsing panniculitis resulting in
      disfiguring lipoatrophy are reported. Histology in both cases showed a mixed
      septal and lobular panniculitis, with lipophagia. The clinical appearance and
      histology suggested a diagnosis of lipoatrophic panniculitis. Both cases had
      features of connective tissue panniculitis, which is likely to be a subtype of
      this condition. Treatment of lipoatrophic panniculitis can be difficult. Our
      first patient initially responded well to antimalarial therapy, allowing plastic
      surgical repair of the defects to be carried out.

PMID- 8251366
TI  - Cowpox can mimic anthrax.
AB  - We report a patient suffering from cowpox infection, in whom the clinical
      features mimicked those of anthrax. The infection may have been acquired as a
      result of contact with a rodent.

PMID- 8251367
TI  - Cowpox infection causing a generalized eruption in a patient with atopic
      dermatitis.
AB  - We report a patient with a history of atopic dermatitis who developed a
      generalized eruption due to cowpox infection. The infection was probably acquired
      from the patient's cat. This is the first report from Britain of cowpox causing
      Kaposi's varicelliform eruption in a patient with atopic dermatitis.

PMID- 8251368
TI  - Photodistributed nifedipine-induced facial telangiectasia.
AB  - Five months after starting nifedipine (Adalat), two patients developed
      photodistributed facial telangiectasia, which became more noticeable with time.
      Neither patient complained of photosensitivity or flushing. Both patients
      reported a significant cosmetic improvement after discontinuing the drug. One
      commenced the closely related drug amlodipine 3 years later, with recurrence of
      telangiectasia. The photodistribution of the telangiectasia suggests a
      significant drug/light interaction.

PMID- 8251369
TI  - Delayed hypersensitivity reaction to heparin.
AB  - We report a patient who developed a delayed hypersensitivity reaction to heparin.
      The literature relating to this type of adverse reaction to heparins is reviewed.

PMID- 8251370
TI  - Detection of human T-cell lymphotropic virus type-1 proviral DNA in the saliva of
      an adult T-cell leukaemia/lymphoma patient using the polymerase chain reaction.
AB  - We report a case of adult T-cell leukaemia/lymphoma (ATLL), in whom the
      polymerase chain reaction (PCR) on genomic DNA from saliva demonstrated the
      monoclonal integration of human T-cell lymphotropic virus type-1 (HTLV-1)
      proviral DNA in lymphocytes in the saliva. These results provided evidence of the
      possibility of saliva-borne transmission of HTLV-1.

PMID- 8251371
TI  - Mechanism of drug-induced inhibition of keratinocyte proliferation: antagonism of
      calmodulin or inhibition of protein kinase C?

PMID- 8251372
TI  - A case of ulerythema ophryogenes responding to isotretinoin.

PMID- 8251373
TI  - Erythema annulare centrifugum induced by molluscum contagiosum.

PMID- 8251374
TI  - Severe exacerbation of rosacea by oral acetazolamide.

PMID- 8251375
TI  - Perianal bowenoid papulosis presenting with pruritus ani.

PMID- 8251376
TI  - Superficial sebaceous hyperplasia of the areolae.

PMID- 8251377
TI  - Genotyping provides a reliable tool for the determination of the platelet antigen
      system HPA-1 in Glanzmann's thrombasthenia.
AB  - Glanzmann's thrombasthenia (GT) is an inherited disorder of platelet function,
      characterized by quantitative or qualitative defects of the platelet glycoprotein
      (GP) IIb/IIIa complex. Patients with GT may require repeated transfusions and
      therefore alloimmunization against platelet antigens could become of particular
      interest. As GPIIIa contains the most important platelet alloantigen system, HPA
      1, its diminished expression in GT patients may impede serological determination
      of the HPA-1 allotype. By immunofluorescence consistent results were obtained in
      only two out of seven patients. The monoclonal antibody-specific immobilization
      of platelet antigen test allowed typing of six patients. DNA analysis was
      feasible in all cases. All seven patients were identified to be homozygous HPA
      1a. Thus, provided a normal HPA-1 DNA region, its analysis can serve as a
      reliable tool for HPA-1 typing in GT even if serological methods fail.

PMID- 8251378
TI  - Reversibility of thrombin-induced decrease in platelet glycoprotein Ib function.
AB  - Thrombin induces a redistribution of glycoprotein (GP) Ib/GP IX complex from the
      platelet surface into the surface connected canalicular system (SCCS). This
      redistribution results in a reduced interaction of platelet GP Ib with von
      Willebrand factor (vWF) bound to subendothelium leading to impaired platelet
      adhesion. In this study we show that the platelet aggregation and degranulation
      require concentrations of thrombin above 0.05 U/ml, while the decrease in GP Ib
      function (about 50% of control value), as determined by ristocetin induced
      platelet agglutination, can be induced by lower concentrations (0.01-0.04 U/ml).
      Moreover, we show that when adding thrombin inhibitors to the platelets
      preincubated with < 0.04 U/ml thrombin for 5 min, their agglutinability by
      ristocetin was gradually recovered within 30 min, indicating that in these
      conditions the decrease in platelet adhesiveness is reversible. Immuno
      electromicroscopic study showed that this restoration of platelet GP Ib function
      was associated with a reversed translocation of GP Ib from the SCCS to the plasma
      membrane. The data obtained from counting gold particles showed that the ratio of
      GP Ib immunolabelling on the external membrane versus that on the SCCS was 3.31
      +/- 0.90 for resting platelets, down-regulated to 0.84 +/- 0.13 (P < 0.05 versus
      resting platelets) for the platelets treated with 0.04 U/ml thrombin and returned
      to 2.63 +/- 2.21 (P > 0.05 versus resting platelets) after incubation for 30 min
      with hirudin. However, the translocation of GP Ib was poorly reversed by thrombin
      inhibitors when higher concentrations of thrombin were used which induced
      platelet aggregation and large extent of degranulation. We conclude that thrombin
      affects platelets in a dose dependent manner, and that at low concentrations the
      decrease in platelet GP Ib related function is a reversible phenomenon.

PMID- 8251379
TI  - Are immunoglobulins with lupus anticoagulant activity specific for phospholipids?
AB  - Recent studies have suggested that the lupus anticoagulant (LA) may be specific
      for prothrombin, prothrombin-phospholipid complexes, or beta 2 glycoprotein 1
      (beta 2GP1) rather than phospholipids. We performed a series of experiments to
      determine whether LA is indeed phospholipid specific. IgG was purified from sera
      of six patients with the antiphospholipid syndrome (APS) and 10 healthy controls.
      The six IgG-APS preparations had both LA and anticardiolipin (aCL) activity.
      Incubation of the six IgG-APS preparations with cardiolipin (CL),
      phosphatidylserine (PS), phosphatidylcholine (PC), or PS/PC (20:80) liposomes in
      Tris-buffered saline, resulted in loss of LA activity from the supernatant. We
      postulated that loss of activity might have resulted from absorption of IgG LA
      antibodies by phospholipids, a dilutional effect, or the presence of
      phospholipids in the supernatant causing 'by-pass' of IgG LA inhibitory activity.
      To distinguish between these possibilities, we re-isolated IgG from the
      supernatants and re-tested them for LA activity. IgG re-isolated from the PS. CL
      and PS/PC supernatants had no LA activity, but LA activity remained in the PC
      supernatant. This suggested that IgG with LA activity was absorbed by negatively
      charged but not by zwitterionic phospholipids. In like manner, PS, CL and PS/PC,
      but not PC liposomes, absorbed IgG with aCL activity. Mixtures of the
      phospholipid liposomes with beta 2GP1 did not modify the absorption of IgG with
      LA or aCL activity. Finally, we demonstrated that IgG eluted from immunoglobulin
      cardiolipin liposome complexes had LA activity. Based on these findings, we
      conclude that at least one population of antibodies with LA activity is
      phospholipid specific.

PMID- 8251381
TI  - A beta zero-thalassaemia due to a 1605 bp deletion of the 5' beta-globin gene
      region.
AB  - We studied a heterozygous beta zero-thalassaemia patient from Croatia with an
      unusually high Hb A2 level of 7.6% and an elevated Hb F level of 5.8%. The same
      condition was found in his father (Hb A2 8.2%; Hb F 8.5%). Gene mapping and
      direct sequencing analyses revealed a new deletion of 1605 bp in the 5' beta
      globin gene region between positions -984/5 and +620/1. This deletion has not
      been observed among more than 500 beta-thalassaemia chromosomes from the Balkan
      countries studied in our laboratory.

PMID- 8251380
TI  - Biological activity of recombinant factor VIII variants lacking the central B
      domain and the heavy-chain sequence Lys713-Arg740: discordant in vitro and in
      vivo activity.
AB  - Recombinant factor VIII variants with overlapping deletions spanning the region
      Lys713-Ile1668 have been expressed in mammalian cells, and analysed for
      biological activity both in vitro and in vivo. Two distinct assay systems were
      used to measure the activity in vitro. The one-stage coagulation assay served to
      assess factor VIII procoagulant activity while a spectrophotometric assay was
      used for the quantification of factor VIII cofactor activity in factor IXa
      dependent factor X activation. Deletion of the entire B-domain (Ser741-Arg1648)
      resulted in a protein with similar procoagulant and cofactor activity. In
      contrast, factor VIII-del(713-1637), which has a deletion that also comprises the
      heavy-chain sequence Lys713-Arg740, had lost factor VIII procoagulant activity
      while factor VIII cofactor activity was retained. This functional inconsistency
      was further addressed by comparing purified factor VIII-del(713-1637) with factor
      VIII-del(868-1562), a mutant with normal in vitro activity. Kinetic studies of
      factor Xa formation revealed that higher concentrations of thrombin were required
      to develop the cofactor activity from factor VIII-del(713-1637) than needed for
      factor VIII-del(868-1562) or plasma factor VIII. The physiological significance
      of this finding was assessed in dogs with haemophilia A. Both deletion mutants
      were similar to plasma factor VIII with regard to binding to von Willebrand
      factor and half-life and recovery. Employing the cuticle bleeding time model,
      factor VIII-del(868-1562) was found to be indistinguishable from plasma factor
      VIII, whereas factor VIII-del(713-1637) was less effective. The increased
      thrombin-resistance of factor VIII-del(713-1637) thus limits both procoagulant
      activity and haemostatic efficacy in cuticle bleeding. These observations suggest
      that the heavy-chain sequence Lys713-Arg740, although dispensable for factor VIII
      cofactor function per se, is involved in the proteolytic activation of factor
      VIII both in vitro and in vivo.

PMID- 8251382
TI  - An IVS-I-117 (G-->A) acceptor splice site mutation in the alpha 1-globin gene is
      a nondeletional alpha-thalassaemia-2 determinant in an Indian population.
AB  - In 1991 we reported the identification of two deletional alpha-thalassaemia-2
      determinants (-3.7 kb and -4.2 kb) and one nondeletional alpha-thalassaemia-2
      determinant (Hb Koya Dora alpha 2 codon 142, TAA-->TCA) in a tribal population in
      Central India (Gupta et al, 1991). Evidence was obtained at that time for the
      possible presence of an additional nondeletional alpha-thalassaemia-2 because of
      low levels of Hb S (< 28%) in some Hb S heterozygotes with a simple alpha
      thalassaemia-2 heterozygosity (-alpha/alpha alpha). This abnormality has now been
      identified as a G-->A mutation at IVS-I-117 of the alpha 1-globin gene (acceptor
      splice site) which makes this gene nonfunctional. Its frequency was established
      at approximately 6% which raises the total frequency of alpha-thalassaemia
      determinants in this population to approximately 60%. Subjects with a deletional
      alpha-thalassaemia-2 and the newly discovered alpha 1 acceptor splice junction
      mutation in trans appear to have an alpha chain deficiency similar to that of an
      alpha-thalassaemia-2 homozygote (-alpha/-alpha). An additional change (C-->G) at
      the Cap -4 site was observed in six alpha 1- and one alpha 2-globin genes; this
      polymorphism is not associated with a decrease in alpha chain synthesis and is
      not linked to the IVS-I-117 (G-->A) mutation.

PMID- 8251383
TI  - Microenvironmentally dependent effects on murine haemopoiesis by a prolonged
      interleukin-1 treatment.
AB  - We administered recombinant human IL-1 beta (400 ng/d, s.c.) for 10 d to normal
      C57B1 mice and determined daily granuloid and erythroid parameters in marrow,
      spleen and blood. In the marrow CFU-GM numbers were not affected but later
      granuloid cell stages were moderately enhanced (170%). In the spleen, however,
      CFU-GM numbers were sharply increased (1600%), whereas the granuloid precursors
      only doubled. Blood granulocytes increased transiently to 275% on day 5. In the
      marrow all erythroid parameters were severely reduced. This reduction was
      partially compensated by the spleen where initially only BFU-E and with some
      delay also more mature erythroid cells accumulated. At the end of the treatment
      mice were slightly anaemic. When mice were treated with IL-1 and erythropoietin
      (10 U/d) simultaneously, the inhibitory effects on erythropoiesis were less
      severe. In agreement with in vivo results, IL-1 inhibited in vitro colony growth
      of CFU-E from normal bone marrow and spleen but spleen CFU-E from 5 d IL-1
      treated mice were insensitive. We conclude that IL-1 can induce stimulation or
      inhibition of haemopoietic progenitor cells depending on their microenvironment.

PMID- 8251384
TI  - Impaired neutrophil chemotaxis in patients with thalassaemia major.
AB  - Random and directed migration, O2- production, degranulation and adhesion were
      studied in neutrophils obtained from patients with homozygous beta-thalassaemia
      and iron overload, in the presence or absence of thalassaemic serum. The only
      significant defect found was an impairment in directed chemotaxis, further
      depressed after addition of thalassaemic serum. The chemotactic defect was
      encountered in all the patients that have suffered from pyogenic infections
      except one, and was not correlated with the severity of the iron overload. It is
      suggested that the described neutrophil migration impairment may contribute to
      the tendency towards infection in certain patients with homozygous beta
      thalassaemia.

PMID- 8251385
TI  - Contrasting interspecies efficacy and toxicology of 1,2-diethyl-3-hydroxypyridin
      4-one, CP94, relates to differing metabolism of the iron chelating site.
AB  - In order to define a predictive animal model for the effects of hydroxypyridinone
      (HPO) iron chelators in humans, we have compared the 28 d oral efficacy and
      toxicology of the HPO, 1,2-diethyl-3-hydroxypyridin-4-one (CP94) in rats and
      guinea-pigs and related the results to the contrasting metabolism of this
      compound in the two species. CP94 was highly effective at mobilizing liver iron
      in rats but showed toxicity at higher doses, whereas in the guinea-pig the
      compound lacked toxicity but was ineffective at mobilizing liver iron. These
      differences can be explained by the contrasting metabolism of the drug between
      the two species. In rats, at the top dose of 300 mg/kg intragastrically, all
      animals died before the end of the study, with no deaths or weight loss at lower
      doses. At 100 mg/kg, rat liver non-haem iron concentrations were reduced by 53%
      and 44% in females and males respectively (P < 0.001). At this dose, adrenal
      medullary cell vacuolation, increased mammary secretory activity, vacuolation of
      corpora luteal cells and single cell hepatocyte necrosis were seen. There were no
      reductions in the white cell count. At 50 mg/kg rat liver non-haem iron
      concentrations were decreased by 50% and 34% in females and males respectively (P
      < 0.02). In female rats this was associated with increased mammary secretory
      activity. In iron-overloaded rats given 100 mg/kg by gavage for 28 d, liver non
      haem iron concentration was reduced by 39% (P < 0.01) and serum ferritin by 71%
      (P < 0.001). Ovarian and mammary changes were not influenced by iron loading. In
      guinea-pigs, CP94 was evaluated at 50 mg/kg, 100 mg/kg or 200 mg/kg by oral
      insufflation for 28 d. No reduction in liver iron was seen and no systematic dose
      related histological, biochemical or haematological effects were observed.
      Whereas in guinea-pigs 99% of urinary recovery following an oral dose of CP94
      (100 mg/kg) was as the inactive glucuronide metabolite, in the rat only 23% of
      the dose was excreted in the urine as the glucuronide with remainder as the free
      drug or an iron binding metabolite. The lack of both efficacy and toxicity in the
      guinea-pig may therefore be explained by the rapid inactivation of CP94 by
      glucuronidation. This metabolism of CP94 in the guinea-pig is closer to humans
      than the rat, suggesting that both the efficacy and toxicity of this compound in
      humans may also be limited by glucuronidation.

PMID- 8251386
TI  - Very early analysis of graft establishment after allogeneic bone marrow
      transplantation using the polymerase chain reaction.
AB  - We have used minisatellite polymorphisms flanking the apolipoprotein B locus and
      PCR to demonstrate the emergence of donor specific alleles in peripheral blood at
      3-7 d post allogeneic bone marrow transplantation (BMT). This technique affords a
      very early indication of the establishment of stable engraftment, and may
      identify patients at risk of graft failure or leukaemic relapse. Patterns of T
      cell chimaerism in the first 7-14 d following transplantation may be closely
      associated with the development of graft-versus-host disease (GVHD), the graft
      versus leukaemia (GVL) effect and graft rejection and future application of this
      technique to the investigation of early T-cell chimaerism may give further
      insights into these immunologically mediated events.

PMID- 8251387
TI  - Treatment of acute monoblastic leukaemia by combination of recombinant human
      macrophage colony-stimulating factor and low dose of ara-C.
AB  - We present a patient with acute monoblastic leukaemia (AMoL) who achieved a
      complete remission on combination therapy with macrophage colony-stimulating
      factor (M-CSF) and low dose of cytosine arabinoside (ara-C). This 26-year-old man
      was admitted with a relapse of AMoL which proved refractory to several
      chemotherapeutic regimens. To kill dormant leukaemic cells, we administered 20
      mg/m2 ara-C by continuous intravenous infusion and 800 x 10(4) unit M-CSF by 30
      min drip intravenous infusion together for 14 d. The blasts disappeared, followed
      by a recovery of normal blood cells. The patient continued the complete remission
      for 5 months. This observation suggests that a combination M-CSF and a low dose
      of ara-C may be useful in treating some patients with AMoL.

PMID- 8251388
TI  - A polymerase chain reaction-based method for the detection of trisomy 12 in B
      chronic lymphocytic leukaemia.
AB  - We report a polymerase chain reaction (PCR)-based method for detection of clonal
      trisomy 12 cell populations in B cell chronic lymphocytic leukaemia which is
      particularly applicable to retrospective analysis or archival material. The
      method utilizes three restriction enzyme site polymorphisms linked to the KRAS2
      locus on chromosome 12 to monitor allele imbalance resulting from duplication of
      this chromosome. 21/24 unselected chronic lymphocytic leukaemia cases (88%) were
      informative for at least one polymorphism and of these, eight (33% of total
      cases) displayed allelic imbalance consistent with trisomy 12.

PMID- 8251389
TI  - Recombinant granulocyte-macrophage colony stimulating factor followed by
      immunosuppressive therapy for aplastic anaemia.
AB  - Seventeen patients with aplastic anaemia were treated with recombinant human
      granulocyte-macrophage colony stimulating factor (rhGM-CSF) for 14 d.
      Nonresponding patients were then treated with anti-human thymocyte globulin
      (ATG), methylprednisolone and oxymetholone. Side-effects of rhGM-CSF included
      fever, nausea and vomiting, diarrhoea, bone pain, headache and chills. Two
      patients had sustained trilineage haemopoietic recovery after receiving only rhGM
      CSF. Of 11 patients who received immunosuppressive therapy, there was one
      complete response, two partial responses, one minimal response, and seven
      nonresponses. Actuarial survival at 2 years is 64%. Early administration of rhGM
      CSF had no apparent effect on subsequent response to immunosuppressive therapy.

PMID- 8251390
TI  - Haemophilia B Liverpool: a new British family with mild haemophilia B associated
      with a -6 G to A mutation in the factor IX promoter.
AB  - We report a Lancashire family with mild haemophilia B associated with a -6 G to A
      mutation in the factor IX promoter. This mutation has been reported previously in
      Britain in one other affected family. The factor IX haplotype of these two
      unrelated patients was determined by PCR analysis of seven polymorphic sites
      within or close to the factor IX gene. This analysis involved the intragenic Msp
      I polymorphism which we have now located precisely to allow the design of
      suitable PCR primers. The haplotype of both of these patients was identical
      suggesting but not proving a possible common origin for the mutation.

PMID- 8251391
TI  - An interstitial deletion in the rearranged T-cell receptor gamma chain locus in a
      case of T-cell acute lymphoblastic leukaemia.
AB  - This report describes the cloning and sequencing of the breakpoint of a deletion
      of approximately 166 bp in the 5' region of a rearranged T-cell receptor gamma
      (TCRG) V gamma 2 gene from the disease cells of a patient with T-cell ALL. This
      abnormal rearrangement was not detected in a biopsy taken during clinical
      remission. Sequence analysis indicated that the deletion breakpoint occurred at a
      position immediately upstream of sequences found in the germline V gamma 2 gene
      that are closely related to known heptamer and nonamer recombination signal
      sequences. Furthermore, the rearrangement was found to have non-germline
      nucleotides (N-region) in between otherwise intact V and J segments. These data
      indicate that this structure may be the result of an aberrant rearrangement event
      in common with the frequently occurring chromosomal abnormalities found in T-cell
      ALL. This event could either be one directly associated with the leukaemic
      transformation or one occurring during normal lymphocyte development but which is
      coincidental with leukaemic transformation. This represents the first molecular
      genetic evidence for an abnormality specifically involving the TCRG locus in ALL.

PMID- 8251392
TI  - Hereditary ovalocytosis with compensated haemolysis.
AB  - The clinical and laboratory phenotype of compensated haemolysis in a patient with
      hereditary ovalocytosis is reported. Clinical presentation was intermittent
      jaundice and abdominal pain due to pigment gall stones. Haematological analysis
      revealed an absolute reticulocytosis with an otherwise normal full blood count
      and biochemical evidence of haemolysis. Variable results were observed with blood
      grouping reagents. The patient's red cells were stomatocytic ovalocytic, rigid,
      resistant to malarial parasite invasion, defective in anion transport, and had
      the characteristic two linked mutations in the red cell band 3 gene.

PMID- 8251393
TI  - Clonal analysis using X-linked DNA polymorphisms.

PMID- 8251394
TI  - Hydroxyurea treatment for chronic myeloid leukaemia during pregnancy.
AB  - A patient being treated for chronic myeloid leukaemia with hydroxyurea became
      pregnant. Despite an increase in the dose of hydroxyurea (to 3 g per day) during
      the pregnancy, her white blood cell count could only be controlled at about 150 x
      10(9)/l. A healthy baby girl was born at 37 weeks with normal blood counts and no
      evidence of congenital abnormality. There are now five reports of the use of
      hydroxyurea in pregnancy, and where leukapheresis is not available it may be the
      treatment of choice.

PMID- 8251395
TI  - Aberrant CD8 antigen expression in a patient with B chronic lymphocytic leukaemia
      showing unusual disease progression.
AB  - Co-expression of T cell antigens in B-CLL has been well recognized. The commonest
      T cell antigen known to be expressed in B-CLL is CD5, and recent reports suggest
      that CD5 expression is associated with good prognosis. Expression of CD8 antigen,
      however, is much less common with uncertain prognostic significance. We report a
      case of B-CLL with aberrant CD8 expression, who had unusual disease progression
      with a fatal outcome.

PMID- 8251397
TI  - Life-threatening thrombotic and haemorrhagic problems associated with silent
      myeloproliferative disorders.
AB  - Myeloproliferative disorders are well recognized as being associated with
      haemorrhage and thrombosis. We describe two cases, one of life-threatening
      haemorrhage and the other of thrombosis, in patients with normal peripheral blood
      counts and films, both of whom went on to develop overt manifestations of
      myeloproliferative disorders (CGL and essential thrombocythaemia) more than a
      year after their first presentation.

PMID- 8251396
TI  - Prognostic value of a novel circulating serum 90K antigen in HIV-infected
      haemophilia patients.
AB  - We evaluated the prognostic role of a novel tumour-associated antigen, termed
      90K, in a cohort of HIV+ asymptomatic haemophilia patients with known duration of
      seropositivity and median follow-up of about 7 years. The circulating levels of
      90K are higher in HIV+ asymptomatic patients than HIV- controls. The antigen
      levels remain quite stable over time in non-progressing patients, while they
      steadily rise in patients evolving to ARC/AIDS. Baseline high 90K levels are
      predictive of faster progression to ARC/AIDS and shorter survival. We conclude
      that an elevated 90K serum level is a predictor of poor prognosis in HIV+
      asymptomatic haemophiliacs.

PMID- 8251398
TI  - Three cases of the myelodysplastic syndrome with pericentric inversion of
      chromosome 16.
AB  - Inversion of chromosome 16, inv(16)(p13q22), is characteristic of acute myeloid
      leukaemia (AML) with eosinophilia and is rarely found in the myelodysplastic
      syndrome (MDS). We report three cases of MDS in which inv(16) was observed. They
      were classified to FAB subtypes RA, RARS and RAEBT; eosinophilia or abnormal
      eosinophils were not observed. The disease appeared to be stable in all three
      patients. MDS with inv(16) without eosinophilia may be a rare subgroup associated
      with a good prognosis.

PMID- 8251399
TI  - Detection of chimaerism after bone marrow transplantation using the double
      amplification refractory mutation system.
AB  - We have developed a highly sensitive double amplification refractory mutation
      system (double ARMS) for the detection of extremely low levels of mixed
      chimaerism after bone marrow transplantation. The system we chose for double ARMS
      analysis is a highly polymorphic region 5' to the human delta-globin gene. Double
      ARMS analysis was found to correlate well with an established minisatellite
      system and was shown to demonstrate a very low level of mixed chimaerism in cases
      undetectable by the latter method.

PMID- 8251400
TI  - HPA-1 typing by PCR amplification with sequence-specific primers (PCR-SSP): a
      rapid and simple technique.
AB  - A DNA-based method was developed to genotype donors for the human platelet
      antigens HPA-1a and -1b. Sequence-specific primers (SSP) were used in the
      polymerase chain reaction (PCR) which allowed the HPA-1a/1a, -1b/1b and -1a/1b
      genotypes to be determined by PCR alone, no second analytical stage was required.
      10 donors were tested by PCR-SSP and the results were concordant with serological
      phenotyping and independent DNA analysis.

PMID- 8251401
TI  - Danazol for myelodysplastic syndromes.

PMID- 8251402
TI  - The deoxyuridine suppression test and cobalamin-folate interrelations.

PMID- 8251403
TI  - Removal of cytomegalovirus (CMV) infected leucocytes from CMV seropositive blood
      units by bedside blood filtration.

PMID- 8251404
TI  - The activity of serum acid phosphatase in bone marrow aspirates predicts response
      to steroids/splenectomy in acute/chronic immune thrombocytopenic purpura.

PMID- 8251405
TI  - Refractory anaemia (RA) type I FAB treated with oxymetholone (OXY): long-term
      results.

PMID- 8251406
TI  - Diagnostic value of immunophenotyping in low-grade B-cell lymphoma.

PMID- 8251407
TI  - Differential sensitivity of human myeloma cell lines and normal bone marrow
      colony forming cells to a recombinant diphtheria toxin-interleukin 6 fusion
      protein.
AB  - The cytotoxicity of a recombinant interleukin 6 (IL-6)-diphtheria toxin (DT)
      fusion protein towards human myeloma cell lines was investigated. DAB389-IL-6
      inhibited protein synthesis and methylcellulose colony formation by U266 myeloma
      cells. In the clonogenic assay, the fusion protein approached the level of
      cytotoxicity achieved by native DT. The specificity of killing by DAB389-IL-6 was
      demonstrated by inhibition of cytotoxicity by a molar excess of free rhIL-6. The
      effect of DAB389-IL-6 on colony formation by six OCI-My cell lines was assessed.
      Similar to U266 cells, colony growth by the OCI-My 5 and -My 2 cell lines was
      inhibited in a simple dose dependent manner. However, a biphasic effect was
      observed for the IL-6 dependent OCI-My 4 cells; DAB389-IL-6 stimulated colony
      formation at low (< or = 10(-11) M) concentrations, yet was inhibitory at higher
      doses. Three other cell lines whose growth was not altered by IL-6 were
      relatively unaffected by DAB389-IL-6, despite their sensitivity to native DT.
      Flow cytometric analysis for IL-6 receptor expression using phycoerythrin
      conjugated IL-6 demonstrated specific binding sites on both DAB389-IL-6 sensitive
      and certain insensitive cell lines, suggesting that other factors in addition to
      the expression of IL-6 receptors are involved in killing by the fusion toxin.
      Despite evidence for a role of IL-6 in myeloid cell development, normal bone
      marrow was insensitive to the IL-6 fusion toxin. In cultures containing both
      normal bone marrow and U266 cells DAB389-IL-6 effectively inhibited the growth of
      U266 myeloma colonies but had little effect on normal bone marrow erythroid,
      granulocyte and mixed erythroid/granulocyte colony growth. From these experiments
      we conclude that DAB389-IL-6 is specifically cytotoxic towards a subset of IL-6
      responsive human myeloma cell lines and may be useful, in some cases, in the
      selective elimination of tumour cells from mixed populations of normal and
      malignant cells.

PMID- 8251408
TI  - Partial engraftment of donor bone marrow cells associated with long-term
      remission of haemophagocytic lymphohistiocytosis.
AB  - We used polymerase chain reaction amplification of minisatellite sequences or of
      a Y chromosome-specific sequence and Southern blotting to analyse long-term
      engraftment (12-82 months) after bone marrow transplantation (BMT) for familial
      haemophagocytic lymphohistiocytosis (FHL). Six children aged from 1 to 18 months
      were transplanted with bone marrow from an HLA-identical sibling in five cases
      and from an HLA-nonidentical related donor (one mismatched HLA antigen) in one.
      The conditioning regiment included VP 16-213 (900 mg/m2), busulfan (16 mg/kg),
      cyclophosphamide (200 mg/kg) and, in one case, aracytine (2 g/m2). Four patients
      are alive without therapy more than 3 years after BMT; the other two relapsed 1
      year after BMT. DNA was extracted from separated polymorphonuclear cells and
      mononuclear cells, as well as from separated E+ and E- cells in one case and
      CD16+ (natural killer) and CD16- cells in two cases. Engraftment was partial in
      the four long-term survivors. Recipient cells were largely predominant in three
      of them as well as in one of the patients who relapsed (the donor also developed
      FHL 18 months after BMT). E+, E-, CD16+ and CD16- cells presented the same
      pattern of chimaerism. Engraftment failed to occur in the patient who received an
      HLA-nonidentical bone marrow. These results indicate that partial engraftment is
      compatible with long-term remission of FHL and that the presence of a small
      proportion of cells of donor origin can prevent FHL-related lymphocyte and
      macrophage activation.

PMID- 8251409
TI  - Dynamic modulation of the cell surface expression of the granulocyte-macrophage
      colony-stimulating factor receptor.
AB  - The GM-CSF receptor (GM-CSFR) is composed of alpha and beta subunits. Surface
      expression of the alpha chain alone leads to low affinity GM-CSF binding and of
      both subunits to high affinity binding; the beta chain is required for
      transducing a proliferative signal. Studies of GM-CSFR expression have
      concentrated largely on static events occurring under conditions of binding
      equilibrium. We have examined the dynamic regulation of high and low affinity GM
      CSFR expression in neutrophils (1100 +/- 200 R/cell, KD 50 +/- 15 pM) and a GM
      CSF dependent human leukaemic cell line, TF-1 (2000 +/- 450 R/cell KD 15 +/- 5
      pM) and 8600 +/- 1150 R/cell KD 1.8 +/- 0.3 nM). The addition of GM-CSF to TF-1
      cells (350 pM, 4 h at 37 degrees C) caused a reduction in subsequent binding of
      125I-GM-CSF at low ligand concentration (100 pM) (following a low pH wash to
      remove surface bound ligand) to 16 +/- 4% and a reduction in binding at high
      ligand concentration (2 nM 125I-GM-CSF) to 36 +/- 9% of control. Scatchard
      analysis showed complete down-regulation of high affinity GM-CSFR and a
      significant reduction in low affinity GM-CSFR. In neutrophils, concentration
      response curves of ligand induced receptor down-regulation at 37 degrees C showed
      that observed down-modulation was more than 10-fold greater than predicted by
      static equilibrium binding data and correlated closely with GM-CSF priming of the
      neutrophil respiratory burst. The addition of IL-3 to TF-1 cells at 37 degrees C
      reduced 100 pM 125I-GM-CSF binding to 18 +/- 4% and 2 nM 125I-GM-CSF binding to
      46 +/- 5% of control. TF-1 cells, but not neutrophils, were able to re-express GM
      CSFR following removal of GM-CSF from medium. TF-1 proliferation assays showed
      that pulsed GM-CSF (0.35-3.5 nM) for up to 4 h did not cause a significant
      increase in 3H-thymidine incorporation which required the continued presence of
      GM-CSF (control 2875 +/- 208 cpm, pulsed GM-CSF 5 ng/ml 4972 +/- 1344, continuous
      GM-CSF 5 ng/ml 17249 +/- 2982). Therefore, proliferation of TF-1 cells required
      the continued presence of GM-CSF at a time when there was no detectable surface
      high affinity GM-CSFR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8251410
TI  - Chronic neutropenia of childhood: frequent association with parvovirus infection
      and correlations with bone marrow culture studies.
AB  - Children with neutropenia of more than 3 months duration often have evidence of
      immune-mediated destruction of mature neutrophils and variable abnormalities of
      myeloid precursors in their bone marrow. These patients often have anti
      neutrophil antibodies which persist for several months. To further investigate
      the aetiology of neutropenia in such patients, bone marrow cells were evaluated
      for the presence of common viruses. Fifteen of 19 patients tested had evidence
      for parvovirus infection by PCR amplification of bone marrow DNA with parvovirus
      specific primers. Of these 15, six also had serologic evidence of parvovirus
      infection. Anti-neutrophil antibodies were identified in nine of 12 patients with
      parvovirus infection. Bone marrow culture studies done on six patients revealed
      varying degrees of myeloid and erythroid inhibition by patient plasma. These
      studies indicate that parvovirus may be a common cause of immune-mediated
      neutropenia in children.

PMID- 8251411
TI  - The prognostic significance of auer rods in myelodysplasia.
AB  - The category of refractory anaemia with excess blasts in transformation (RAEBt)
      of the French-American-British (FAB) classification system comprises a
      heterogeneous group of patients: those with any combination of 5% or more blood
      blast cells, more than 20% but no more than 30% marrow blast cells, or the
      presence of auer rods and 30% or less marrow blast cells. To determine the
      prognostic significance of auer rods in RAEBt, we classified the 208 patients
      with RAEBt seen between 1973 and 1992 as (1) those having RAEBt solely on the
      basis of auer rods (RAEBta, n = 29), (2) those meeting blood or marrow blast
      criteria for RAEBt and also having auer rods (RAEBtpos, n = 40) or (3) those
      meeting blood or marrow blast criteria for RAEBt without having auer rods
      (RAEBtneg, n = 139). The RAEBta group had a higher survival probability than
      either of the other two groups. Within RAEBta, those patients who, without auer
      rods, would be considered RAEB by the FAB system (n = 19) had a higher
      probability of survival than patients with RAEB as conventionally defined.
      Furthermore, patients with RAEBtpos were more likely to live longer than those
      with RAEBtneg. The RAEBta, RAEBtpos and RAEBtneg groups were similar with regard
      to the usual haematologic parameters. However, patients with auer rods were more
      likely to have a normal karyotype and less likely to have prognostically
      unfavourable cytogenetic abnormalities. When analysis was performed within
      cytogenetic groups, the favourable prognostic impact of auer rods was still
      evident. Similarly, the favourable prognostic significance of auer rods was
      discernible both among patients who did not receive intensive therapy and those
      who received induction chemotherapy. The complete remission rate in auer rod
      positive patients was 77%, compared to 27% in those without auer rods. There were
      no differences in remission duration. Our results suggest that: (1) patients with
      auer rods without blood or bone marrow blast criteria for RAEBt should not be
      grouped with those patients with such criteria, and (2) patients with auer rods
      and other criteria for RAEBt have a higher complete remission rate following
      induction therapy of the type frequently reserved for patients with acute myeloid
      leukaemia.

PMID- 8251412
TI  - Recombinant interferon alfa 2a in the treatment of patients with early stage B
      chronic lymphocytic leukaemia.
AB  - 18 patients with early stage, previously untreated B-CLL were given interferon
      alfa (IFN alpha) 2a. 3 MU thrice weekly, subcutaneously. The peripheral
      lymphocyte count decreased in all patients. Response was delayed in three
      patients until they had received a median of 5 months therapy, one of whom had an
      initial transient increase in lymphocytes. Two patients normalized their blood
      lymphocyte counts, but neither achieved complete remission (CR). Responses were
      transient in eight patients lasting a median of 5 months (3-21). Binding anti-IFN
      alpha antibodies were present in 9/17 patients tested (53%). Low titre binding
      antibodies (< 533 IBU/ml) were not associated with LHR, but high titre antibodies
      (> 4401 IBU/ml) were. Two of 12 patients assessed had a > 3 g/l increase in
      baseline serum IgG levels during IFN alpha therapy, one of whom reverted to
      pretreatment levels in association with LHR. Haematological toxicity was
      moderate, other than in two patients, one of whom developed autoimmune haemolytic
      anaemia and the other thrombocytopenia. We conclude that IFN alpha lowers the
      lymphocyte count in early stage CLL, that the response may be delayed and that
      anti-IFN alpha antibodies may play a role in a proportion of those in whom the
      response is transient.

PMID- 8251413
TI  - Results of Medical Research Council trial UKALL IX in acute lymphoblastic
      leukaemia in adults: report from the Medical Research Council Working Party on
      Adult Leukaemia.
AB  - The MRC UKALL IX trial for patients with untreated ALL aged 14 years and over was
      open to new patients from July 1980 to April 1985. 266 patients were randomized
      between two induction schedules. M (involving intermediate dose methotrexate with
      folinic acid rescue) and D (involving daunorubicin). Schedule M resembled that
      used in the previous MRC adult ALL trial (UKALL VI), while schedule D was
      somewhat more intensive. No difference in disease-free survival was found between
      the treatment arms, but patients on the daunorubicin arm went into remission
      earlier. The overall remission rate was 87%, which is at least as good as in
      contemporary studies elsewhere; factors predictive of a lower remission rate were
      older age and higher WBC. For those who entered remission. WBC, age and sex were
      the most important prognostic factors. Time to achieve remission was not a
      significant factor after allowance was made for these. An historical comparison
      does not show any improvement over the preceding MRC adult trial, although the
      subsequent trial does show a modest improvement at present. Because the improved
      outlook seen in children is not apparent in adults, and no other randomized trial
      has demonstrated substantial benefit for any particular regimen, the next trial,
      UKALL XII, will be investigating the benefit or otherwise of bone marrow
      transplantation.

PMID- 8251414
TI  - Fanconi's anaemia and its variability.

PMID- 8251415
TI  - High incidence of lymphoid infiltration on labial salivary gland biopsy in non
      Hodgkin's lymphomas: clinical implications.
AB  - Sjogren's syndrome (SS) is characterized by an increased risk of developing a non
      Hodgkin's lymphoma (NHL). We performed labial salivary gland biopsy (LSGB) in 103
      patients with untreated NHL, negative for human immunodeficiency virus. Median
      age was 58 years (range 21-79) and M/F 1.3. Using the Working Formulation, 37
      patients had low-grade NHL and 66 had intermediate- or high-grade NHL. Dense
      lymphocytic infiltration (positive focus score 3 or 4) was found in 28 patients.
      10 (35%) of these 28 patients fulfilled criteria for possible SS. 15/28 patients
      had an identical monotypic infiltrate on LSGB and NHL tissue (including two of
      the 10 patients with criteria for SS). The significance of the lymphoid
      infiltrate of LSGB was unknown in the five remaining patients with positive focus
      score. Significant correlations were found between positive focus score and
      presence of two or more extranodal sites of disease (P = 0.02), impaired
      performance status (P = 0.004), splenomegaly (P = 0.05), increased gammaglobulin
      level (P = 0.03), and beta 2 microglobulin (P = 0.004). Considering intermediate-
      or high-grade NHL, we found significant correlation between positive focus score
      and unfavourable prognosis according to the two Dana Farber Cancer Institute
      indexes (P < 0.04), to the LNH-84 index (P = 0.05), and to the international
      index (P = 0.003). In conclusion, systematic evaluation of LSGB in 103 patients
      with NHL found lymphoid infiltration in 28% of them, but possible SS could be
      considered in only 10%. This lymphoid infiltration, though not correlated with
      any particular histological subtypes, was associated with unfavourable clinical
      prognostic factors, especially in intermediate- or high-grade NHL.

PMID- 8251417
TI  - The origin and significance of our supplements--a response to the New England
      Journal of Medicine.

PMID- 8251416
TI  - B-cell lymphoma of recipient origin 9 years after allogeneic bone marrow
      transplantation for T-cell acute lymphoblastic leukaemia.
AB  - A 25-year-old woman developed an immunoblastic lymphoma 9 years after HLA
      identical allogeneic bone marrow transplantation for T-cell acute lymphoblastic
      leukaemia in second remission. The B-cell origin of the second malignancy was
      confirmed by gene rearrangement studies. Despite continued donor engraftment, two
      separate genotypic analyses identified the lymphoma to be of recipient origin.
      This is the longest latency of a post-transplant recipient lymphoma yet reported
      and illustrates that recipient B-cells may survive the transplant conditioning
      regimen and undergo malignant transformation in the presence of donor
      haemopoiesis.

PMID- 8251418
TI  - Effects of glibenclamide upon ATP-sensitive K channels during metabolic
      inhibition of isolated rat cardiac myocytes.

PMID- 8251419
TI  - Metabolic regulation of cardiac ATP-sensitive K+ channels.
AB  - Activation of ATP-sensitive K+ (KATP) channels has been implicated as a cause of
      increased cellular K+ efflux and action potential duration (APD) shortening
      during myocardial ischemia, hypoxia, and selective glycolytic inhibition, since
      selective KATP channel antagonists partially or completely block increased
      cellular K+ efflux and APD shortening under these conditions. During substrate
      free hypoxia or myocardial ischemia in intact rabbit ventricle, unidirectional K+
      efflux rate during systole approximately doubled and APD decreased by
      approximately 40% after 10 minutes. In patch-clamped guinea pig ventricular
      myocytes, similar changes could be produced by activation of < 0.5% of the
      maximal KATP channel conductance. Furthermore, from studying the desensitizing
      effects of ADPi on the ATP sensitivity of KATP channels in excised inside-out
      patches, it was estimated that the rapid changes in the cytosolic ATP/ADP ratio
      during ischemia and hypoxia were of sufficient magnitude to activate KATP
      channels to this degree. During selective glycolytic inhibition, however, the
      global cytosolic ATP/ADP ratio in intact heart remained normal despite an
      increase in cellular K+ efflux comparable to ischemia and hypoxia. In patch
      clamped saponin-permeabilized ventricular myocytes, KATP channels were
      preferentially suppressed by glycolytic ATP production compared to ATP generated
      by mitochondria or by the creatinine kinase reaction, and functional glycolytic
      enzymes were found to be associated with KATP channels in excised membrane
      patches. We hypothesize that sarcolemma-associated glycolytic enzymes may be
      important in maintaining a high local cytosolic ATP/ADP ratio in the vicinity of
      KATP channels, where sarcolemmal ATPases are tending to depress the local ATP/ADP
      ratio.

PMID- 8251420
TI  - Modulation of ischemia by regulation of the ATP-sensitive potassium channel.
AB  - During acute myocardial ischemia, passage of potassium ions across the sarcolemma
      to the extracellular space is a well-established phenomenon. A recent hypothesis
      is that the ATP-dependent potassium channel plays a role in contributing to the
      potassium loss. As the potassium loss starts while the overall level of ATP is
      still relatively high, and as the channel is inhibited by rather low
      concentrations of ATP, the question arises as to how the channel is opened. Among
      the proposals are that, in addition to the total concentration of ATP, there is
      modulation of the regulation by its breakdown products, such as ADP and
      adenosine. Alternatively, or in addition, breakdown products of anaerobic
      glycolysis, such as lactate and protons, may also play a role. Extracellular
      acidosis may help to activate the channel, and internal lactate accumulation may
      have a similar effect. In certain circumstances there is evidence that ATP
      produced by glycolysis plays a significant role in the control of potassium
      channel activity. The concept of subsarcolemmal ATP is another explanation for
      the activation of the channel at relatively high ATP concentrations. Potassium
      channel closing drugs, such as glibenclamide, may prolong the action potential
      duration (shortened by ischemia) and thereby decrease the incidence of early
      ventricular arrhythmias. This same category of drugs may reduce early potassium
      loss from the ischemic tissue, thereby lessening the potentially protective
      effect of the external accumulation of potassium on the ischemic zone, the so
      called local cardioplegic effect. Conversely, drugs of the potassium channel
      activating group are likely to have opposite effects on these arrhythmias and on
      myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251421
TI  - Gating properties of ATP-sensitive K+ channels in the heart.
AB  - Using a concentration jump technique (oil-gate method), the rate of closure or
      opening of the ATP-sensitive K+ channel was measured in response to varying the
      ATP concentration. The inside-out patch was prepared from dissociated ventricular
      cells of guinea-pig heart. The opening of the channel on jump to ATP-free
      solutions from various ATP concentrations showed a variable latent period before
      the almost exponential rise of the mean channel current. The mechanism of latency
      is not clear. On reapplying ATP, the channel closed without any obvious delay,
      and the time course was well fitted with a single exponential curve. The
      reciprocal time constant was proportional to the ATP concentration. The closing
      rate was explained by assuming a 1:1 binding stoichiometry and a rate constant of
      51.7 or 5.6 mM-1s-1.

PMID- 8251422
TI  - Role of ATP-sensitive K+ channel current in ischemic arrhythmias.
AB  - In acute myocardial ischemia slow conduction and short refractoriness both
      predispose to cardiac arrhythmias. Moreover, spatial dispersion in these
      parameters, in part determined by inhomogeneity in extracellular potassium
      concentration ([K+]0), which develops within minutes, is considered highly
      arrhythmogenic. The incidence and time distribution of ventricular arrhythmias is
      determined by these electrophysiological changes and by factors pertinent to the
      experimental model. In the initial phase of ischemia, glibenclamide, a potent
      blocker of ATP-sensitive K+ channels (K+ATP channels), reduces the rate of
      increase in [K+]0 and therefore, presumably, also the inhomogeneity in [K+]0.
      During this phase of ischemia glibenclamide has an antiarrhythmic effect, which
      may be based on a reduction in inhomogeneity in [K+]0. In addition, glibenclamide
      prolongs the action potential of ischemic myocardium. Although under ischemic
      conditions action potential duration is no longer a reliable parameter or
      refractoriness, glibenclamide-induced prolongation or refractoriness may play a
      role in the prevention of arrhythmias. In contrast, openers of K+ATP channels
      increase the incidence of ventricular arrhythmias or, in other models, the time
      course of onset is accelerated. They shorten the duration of the action potential
      in ischemic tissue. In the globally ischemic rabbit heart, initial changes in
      [K+]0 are not influenced by cromakalim. It is concluded that activation of the
      K+ATP channel current during early myocardial ischemia potentially contributes to
      the development of ventricular arrhythmias. Particularly, the direct
      electrophysiological effect of increased K+ current is considered arrhythmogenic.

PMID- 8251423
TI  - ATP-sensitive K+ channels in cardiac ischemia: an endogenous mechanism for
      protection of the heart.
AB  - The Role of ATP-sensitive K+ channels (KATP) in action potential shortening and
      protection of myocardium in ischemia were explored using isolated ventricular
      myocytes and arterially perfused right ventricular walls of guinea pigs.
      Conditions "simulating" some aspects of ischemia--(10.8 mM K+o, 6.9 pHo, 20 mM
      lactate, no glucose; 10 mM 2-deoxy-D-glucose; and either 1 mM cyanide or no O2
      (bubbled with 95/5% N2/CO2)--caused a decline in action potential duration (APD)
      and the elaboration of time- and voltage-independent, steady-state outward
      conductance due to KATP, which could be inhibited with glibenclamide (50 microM)
      in myocytes studied via the perforated patch (nystatin) whole-cell technique.
      Right ventricular walls subjected to no-flow ischemia +/- glibenclamide (10
      microM) to block, or +/- pinacidil (1 and 10 microM) to activate, KATP,
      respectively, exhibited varied ischemic injury. Glibenclamide caused a greater
      fall in resting membrane potential, inhibited the decline in APD, caused an early
      rise in resting tension, and inhibited recovery of contractile function upon
      reflow. Pinacidil caused a greater decline in APD, inhibited changes in resting
      tension, and improved recovery during reperfusion. These results indicate that
      KATP contributes to action potential shortening in isolated myocytes in simulated
      ischemia and intact myocardium in no-flow ischemia. Activation of this membrane
      current may be an important adaptive mechanism for protecting the myocardium when
      blood flow to the tissue is compromised.

PMID- 8251424
TI  - K channel openers activate different K channels in vascular smooth muscle cells.
AB  - The properties of K channels activated by K channel openers (nicorandil,
      cromakalim, pinacidil, etc.) were investigated using conventional microelectrode
      and patch-clamp methods. In single smooth muscle cells of the rat and rabbit
      portal veins, K channel openers produced an outward current sensitive to
      glibenclamide, 4-AP, and TEA (1 mM), but insensitive to apamin and charybdotoxin.
      Glibenclamide-sensitive K channels in both tissues had a small unitary
      conductance (10 pS and 15 pS) and were inhibited by intracellular ATP. The
      activity of the 15 pS channel in the rabbit portal vein was not changed by an
      increase in the intracellular free Ca concentration, but the activity of the 10
      pS channel in the rat portal vein was markedly modified by Ca concentration.
      These results coincided with previous observations using a conventional
      microelectrode and whole-cell voltage-clamp experiments. In the inside-out
      membrane patch, the 10 pS channel in the rat portal vein was activated by the
      application of K channel openers, while the 15 pS channel in the rabbit portal
      vein was rapidly inactivated, even in the presence of K channel openers. GDP, but
      neither GTP gamma S nor GDP beta S, reopened the 15 pS channel in the presence of
      K channel openers. These results suggested that the 15 pS channel had two channel
      states, that is, both operative and inoperative states, while the 10 pS channel
      did not have an inoperative state. The K channel openers open the ATP-sensitive K
      channel only at the operative state.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251425
TI  - Therapeutic potential of potassium channel openers in peripheral vascular disease
      and asthma.
AB  - Potassium channel opener's (KCOs) were originally thought of as nonselective
      smooth muscle relaxants. However, recent investigations in animal models of both
      peripheral vascular disease (PVD) and asthma have revealed interesting effects of
      these drugs as unexpectedly low doses. Hemodynamically, KCOs are interesting in
      PVD since they have little effect on blood supply to normally perfused skeletal
      muscle, but enhance perfusion to chronically ligated ischemic tissue. In animal
      PVD models, SDZ PCO-400 and cromakalim have been shown to improve recovery of
      muscle energy stores from ischemia or to preserve performance under conditions of
      ischemic contracture. Beneficial effects in rat PVD models were manifest at doses
      below those affecting systemic blood pressure and may be attributable to a
      selective dilatation of collateral vessels. With regard to the airways, the
      apparent efficacy of KCOs as antiasthmatic drugs seems not to be attributable
      solely to their bronchodilator activity. Although KCOs elicit no antiinflammatory
      effect in animal models, studies with SDZ PCO-400 in guinea pigs sensitized to
      antigen or treated with immune complexes have revealed that expression of airway
      hyperreactivity is significantly inhibited at drug doses exhibiting only modest
      bronchodilator activity. At least part of this action can be attributed to
      inhibition at the level of neural innervation of the airways, possibly through
      attenuation of nonadrenergic noncholinergic (NANC) transmission.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8251426
TI  - Hyperpolarization induced by K+ channel openers inhibits Ca2+ influx and Ca2+
      release in coronary artery.
AB  - The vasodilating mechanisms of the K+ channel openers--cromakalim, pinacidil,
      nicorandil, KRN2391, and Ki4032--were examined by measurement of the cytoplasmic
      Ca2+ concentration ([Ca2+]i) using the fura-2 method in canine or porcine
      coronary arterial smooth muscle. The five K+ channel openers all produced a
      reduction of [Ca2+]i in 5 and 30 mM KCl physiological salt solution (PSS), the
      effects of which were antagonized by tetrabutylammonium (TBA) or glibenclamide,
      but failed to affect [Ca2+]i in 45 and 90 mM MCl-PSS. Cromakalim and Ki4032 only
      partially inhibited the 30 mM KCl-induced contractures, whereas pinacidil,
      nicorandil, and KRN2391 nearly abolished contractions produced by high KCl-PSS.
      The increased [Ca2+]i and force produced by a thromboxane A2 analogue, U46619,
      were inhibited by K+ channel openers and verapamil. In the absence of
      extracellular Ca2+, U46619 induced a transient increase in [Ca2+]i with a
      contraction, which is effectively inhibited by cromakalim and Ki4032. Their
      inhibitory effects were blocked by TBA and counteracted by 20 mM KCl-induced
      depolarization. Cromakalim and Ki4032 did not affect caffeine-induced Ca2+
      release. Cromakalim reduced U46619-induced IP3 production and TBA blocked this
      inhibitory effect. Thus, cromakalim and Ki4032 are more specific K+ channel
      openers than pinacidil, nicorandil, and KRN2391. The vasodilation related with a
      reduction of [Ca2+]i produced by K+ channel openers is due to the
      hyperpolarization of the plasma membrane resulting in not only the closure of
      voltage-dependent Ca2+ channels but also inhibition of the production of IP3 and
      Ca2+ release from intracellular stores related to stimulation of the thromboxane
      A2 receptor.

PMID- 8251427
TI  - Differential mechanism of block of palmitoyl lysophosphatidylcholine and of
      palmitoylcarnitine on inward rectifier K+ channels of guinea-pig ventricular
      myocytes.
AB  - We investigated the effect of lysophosphatidylcholine (lysoPtdCho) and
      palmitoylcarnitine (PamCar), ischemia-induced amphipathic lipid metabolites, on
      the inward rectifier K+ channel in guinea-pig ventricular cells, under whole-cell
      and cell-attached configurations with patch-clamp techniques. (a) Both lysoPtdCho
      (10-50 microM) and PamCar (10-50 microM) depolarized the resting membrane
      potential (RP), retarded the repolarization of action potential, provoked
      spontaneous action potential discharges from oscillatory afterpotentials, and
      eventually caused a sudden rise of the RP to plateau levels. (b) These lysoPtdCho
      or PamCar-induced depolarizations of RP were due to a decrease in the inward
      rectifier K+ current (IK1), and the sudden rise of the RP could be accounted for
      by a crossover of N-shaped current-voltage relationship on the voltage axis (zero
      current line) more than once. (c) Single-channel studies in the cell-attached
      mode revealed that lysoPtdCho (5-100 microM) decreased the conductance of the
      single IK1 channel with little change in its open probability, whereas PamCar (10
      50 microM) did so by decreasing the open probability, with the channel
      conductance unaltered. (d) A short-chain acylcarnitine, l-propionylcarnitine
      (PpCar, 100 microM), prevented the depressant effect of lysoPtdCho (50 microM),
      but not of PamCar (50 microM), on the IK1. (e) Both lysoPtdCho and PamCar
      produced identical electrophysiological alterations on the membrane potential and
      IK1 in whole-cell recordings. However, molecular mechanisms involved in the
      effects of these toxic metabolites on single IK1 channels differ.

PMID- 8251428
TI  - Activation and reactivation of the ATP-sensitive K+ channel of the heart can be
      modified by drugs.
AB  - Activation and reactivation of the ATP-sensitive K+ channel (IK.ATP) were studied
      with the patch-clamp technique in guinea-pig ventricular myocytes. The K+ channel
      openers, nicorandil and pinacidil, activated IK.ATP in an internal ATP-dependent
      manner. Both drugs increased the open probability of IK.ATP without changing the
      channel conductance. They prolonged lifetimes of bursts and shortened interburst
      intervals without influencing the fast gating within bursts. These effects were
      the opposite of those of internal ATP. However, the interaction between ATP and
      either nicorandil or pinacidil appeared not to be simple competition. We found
      that three carbonyl compounds--3,4-dihydroxybenzaldehyde, 2,3
      dihydroxybenzaldehyde, and 2,4-dihydroxyacetophenone--could activate IK.ATP
      through an intracellular mechanism that was dependent upon the presence of ADP
      and Mg2+. It has been suggested that these three carbonyl compounds bind
      covalently to proteins to form a Schiff base, which may be responsible for their
      effects upon IK.ATP. Internal application of the proteolytic enzyme trypsin
      prevented both the spontaneous and Ca(2+)-induced rundown of the KK.ATP channel.
      Tryptic digestion did not change either the channel's sensitivity to inhibition
      by ATP nor the fast gating kinetics of IK.ATP. Internal application of an
      exopeptidase, carboxypeptidase A, but not leu-aminopeptidase, prevented the
      spontaneous and Ca(2+)-induced rundown of the IK/ATP channel, effects similar to
      those of trypsin treatment. These results suggest that the target site of trypsin
      digestion may be located on the carboxy (C)-terminal of the channel proteins or
      associated regulatory units.

PMID- 8251429
TI  - Use-dependent block of the delayed K+ current in rabbit ventricular myocytes.
AB  - Block of the delayed K+ current, iK, and the concomitant increase in
      refractoriness is considered an alternative to a decrease of conduction in the
      treatment of reentry arrhythmias. Ideally an agent should selectively prolong the
      action potential at high frequencies. A minimum requirement is use-dependent
      block. A number of drugs were tested for the existence of use dependence by
      applying a train of depolarizing clamps to single cardiac myocytes of the rabbit
      ventricle. Development of block during a long depolarizing clamp and recovery
      from block were also measured. Five of the nine drugs tested, i.e., disopyramide,
      encainide, quinidine, sotalol, and tedisamil, did not show use dependence. When a
      train of depolarizing clamps was applied, block was already present for the first
      depolarization and did not increase with repetition of the pulse. This result
      suggests block of the channel in the rested state or a very fast block of the
      open channel. Almokalant and amiodarone, and to a lesser extent dofetilide and
      E4031, showed use-dependent block, i.e., block increased during the train of
      depolarizing clamps. The time constant for the open channel block was 1.07
      seconds for almokalant and 0.67 seconds for amiodarone. Recovery from block for
      almokalant and amiodarone was very slow: time constants measured at -50 mV were
      13.9 and 12.7 seconds, respectively. For dofetilide it was in the order of
      minutes. The existence of this slow recovery explains why frequency-dependent
      changes in block were negligible or absent for frequencies above 0.5 Hz. Future
      research should be aimed to select drugs with a slower onset of active state
      block and faster recovery from block.

PMID- 8251430
TI  - Regulation of arterial tone by calcium-dependent K+ channels and ATP-sensitive K+
      channels.
AB  - Resistance arteries depolarize and constrict to elevations in intravascular
      pressure. However, many of the molecular aspects of this phenomenon are not
      known. We present evidence that large conductance calcium-dependent potassium
      (KCa) channels, which are activated by intracellular calcium and membrane
      depolarization, play a fundamental role in regulating the degree of intravascular
      pressure-induced, myogenic tone. We found that blockers of KCa channels,
      charybdotoxin (CTX, < 100 nM) and TEA+ (< 0.5 mM), further depolarized
      pressurized arteries by as much as 12 mV and decreased diameter by up to 40%. CTX
      blocked KCa channels in outside-out patches from arterial smooth muscles with
      half-block constant of 10 nM and external TEA+ caused a flickery block, with a
      half-block constant of 200 microM. We propose that KCa channels serve as a
      negative feedback pathway to limit the degree of membrane depolarization and
      hence vasoconstriction to pressure. In contrast, CTX and TEA+ (< 1 mM) were
      without effect on membrane hyperpolarization and dilation to a wide variety of
      synthetic (cromakalim, pinacidil, diazoxide, minoxidil sulfate) and endogenous
      agents [calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide, an
      endothelial-derived hyperpolarizing factor]. Glibenclamide and low concentrations
      of external barium that inhibit ATP-sensitive potassium (KATP) channels, however,
      blocked the hyperpolarizations and dilations to these substances. We have
      identified KATP channels as well as high-affinity glibenclamide binding sites in
      arterial smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251431
TI  - Enhanced functional expression of transient outward current in hypertrophied
      feline myocytes.
AB  - Cardiac hypertrophy can decrease myocardial contractility and alter the
      electrophysiological activity of the heart. It is well documented that action
      potentials recorded from hypertrophied feline ventricular cells can exhibit
      depressed plateau voltages and prolonged durations. Similar findings have been
      made by others in rabbit, rat, guinea pig, and human heart. Whole-cell patch
      voltage-clamp studies designed to explain these changes in the action potential
      suggest that the only component of the membrane current recorded from feline
      right ventricular (RV) myocytes found to be substantially different from normal
      is the 4-amino-pyridine-sensitive transient outward current (I(to)). However, it
      was not clear if the change in I(to) could explain the changes in the action
      potential of hypertrophied cardiocytes, nor was it clear if these changes reflect
      an alteration in the electrophysiological character of the channels underlying
      I(to). A kinetic comparison of I(to) elicited by hypertrophied RV myocytes with
      that elicited by comparable normal RV myocytes previously revealed no
      differences, suggesting that the increased magnitude of the peak I(to) recorded
      from hypertrophied myocytes arises because the current density increases and not
      because of any alteration in the kinetic parameters governing the current. This
      finding suggests that in hypertrophy additional normal channels are expressed
      rather than a kinetically different channel subtype emerging. Investigations
      designed to determine if enhancement of I(to) could explain the hypertrophy
      induced changes in plateau voltage and action potential duration suggest that a
      change in I(to) density can indeed explain the entire effect of hypertrophy on RV
      action potentials. If this notion is correct, the likelihood of "sudden death" in
      patients with myocardial hypertrophy might be decreased by a blocker selective
      for cardiac I(to).

PMID- 8251432
TI  - Effect of E-4031, a new class III antiarrhythmic drug, on reentrant ventricular
      arrhythmias: comparison with conventional class I drugs.
AB  - We evaluated the antiarrhythmic efficacy of E-4031, a new class III drug, and
      compared it with that of conventional class I and II antiarrhythmic agents in
      terms of electrophysiological actions on refractoriness and conduction in a 7-day
      old canine model of myocardial infarction. Sustained monomorphic VT was
      reproducibly induced in 26 dogs by a premature stimulation method from the right
      ventricle. Class I drugs (disopyramide, aprindine, flecainide) prevented VT
      induction in 5 of 13 dogs, and propranolol and E-4031 prevented it in 6 of 6 and
      6 of 7 dogs, respectively. The effective refractory period (ERP) was determined
      at 47 epicardial sites overlying the infarct in each experiment by a S1S2 method.
      The standard deviation (SD) of the mean ERP of these sites was used as an index
      of ERP dispersion. The extent of ERP prolongation produced by class I drugs and E
      4031 was significantly more marked than that produced by propranolol. However,
      the SD was increased by class I drugs and E-4031, but not by propranolol. Class I
      drugs increased the ERP dispersion mainly by an effect on the transmural infarct
      zone in which the control ERP was more prolonged than in the normal zone. E-4031
      tended to prolong the ERP in both the normal and infarct zones, and had a minimal
      tendency to increase ERP dispersion. In contrast, propranolol decreased the ERP
      dispersion between zones. Conduction velocity calculated by epicardial mapping
      was significantly decreased by flecainide, but not by E-4031. We conclude that
      the antiarrhythmic effect of E-4031 depends largely on its ability to prolong
      refractoriness without suppressing conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251434
TI  - Ambiguous plaids: switching between coherence and transparency.
AB  - A plaid pattern consisting of two differently oriented moving gratings can be
      seen as two alternative percepts: transparency, in which the two gratings are
      seen to slide over each other in their respective directions, or coherence, in
      which one integrated pattern (the plaid) is seen to move in a new direction. With
      prolonged inspection, an observer switches between these two alternatives. It was
      found here that adaptation to unambiguous coherence reduces the time that
      coherence is seen with an ambiguous test stimulus. Similarly, adaptation to
      transparency reduces the time transparency is seen. Analysis of the duration of
      consecutive episodes revealed that the underlying processes are adapted
      independently. Control experiments confirmed that adaptation occurred to the
      coherent plaid and not to the intersections, and that this adaptation was not
      simply a directional motion aftereffect. It is concluded that switching occurs
      between motion processes at different cortical levels that can be adapted
      independently.

PMID- 8251433
TI  - Delayed rectifier potassium channels in ventricle and sinoatrial node of the
      guinea pig: molecular and regulatory properties.
AB  - We focus on the regulatory properties of delayed rectifier K+ (IK) channels in
      guinea-pig sinoatrial node (SAN) and compare SAN IK to the better characterized
      ventricular IK. Despite demonstrated similarities in the properties of IK in
      guinea-pig ventricle and SAN, the possibility remains that expression of IK
      channels can vary regionally within the same heart. Like ventricular IK, SAN IK
      can be enhanced by beta-adrenergic stimulation and exposure to phorbol ester.
      However, in contrast to ventricular IK, regulation of SAN IK by protein kinases A
      and C is not temperature dependent. Basal SAN IK can be diminished by muscarinic
      agonists, while beta-adrenergic stimulation is a precondition for reduction of
      ventricular IK by cholinergic agonists. Nonstationary state fluctuation analysis
      predicts a small single-channel current (1 pA) and a large number of functional
      channels (308) associated with whole-cell SAN IK. The corresponding single
      channel conductance of 6 pS is somewhat larger than that estimated for
      ventricular IK. Overall comparisons of guinea-pig ventricular and SAN IK to the
      current associated with the minK channel clone suggest that the native guinea-pig
      cardiac IK channels may be related not only to each other but lso to the minK
      channel protein.

PMID- 8251435
TI  - Bright lines and edges facilitate the detection of small light targets.
AB  - Thresholds for the detection of a small light target (increment thresholds),
      measured at the ends of white lines and small luminance edges, are lower than
      when the target is presented on a plain field. This facilitation effect
      disappears when: (1) the line-end is 'stopped' by another line with perpendicular
      orientation; (2) the inducing line is black instead of white; and (3) when the
      inducer does not carry information about orientation (e.g., a small dot). These
      observations suggest that polarity specific and orientation selective neural
      activation, extending collinearly from the inducing lines and edges, produces a
      local increase in visual sensitivity. The possible role of such a mechanism in
      contour completion and the formation of illusory contours is discussed.

PMID- 8251436
TI  - The effect of disparity on motion coherence.
AB  - Many moving plaid stimuli are ambiguous, and perception switches between a
      coherent plaid pattern and two transparent gratings. Here, experiments are
      reported that examined the effect of stereodepth between the two gratings of the
      moving plaid stimulus on the perception of coherence or motion transparency.
      Increasing disparity increased the percentage of time that two independently
      drifting transparent gratings were perceived. This was studied for plaids with
      various levels of intersection luminance. Using intersection luminances beyond
      conditions of physical transparency increased the percentage of time that one
      coherent plaid was seen. These two opposing influences could be pitted against
      each other to achieve constant levels of coherence. An adaptation paradigm was
      also used in which observers adapted to a stationary stimulus with either zero,
      crossed or uncrossed disparity between the gratings, and then indicated the
      occurrence of coherence and motion transparency in test stimuli of drifting
      plaids with zero, crossed or uncrossed disparity. Adaptation to crossed and
      uncrossed stereo-depth increased relative perceived coherence equally, especially
      for zero test disparity. An analysis of the length of the episodes of coherence
      and motion transparency indicated that the effect of adaptation was to decrease
      the length of motion transparency episodes, while the length of coherence
      episodes did not change. It is concluded that mechanisms involved in the
      processing of stereo-depth must have an input to the integration stage of the
      motion channel and that pattern and component motion mechanisms can operate quite
      independently.

PMID- 8251437
TI  - A neural model of discrete and continuous modes of visual discrimination.
AB  - A simple neural model of visual pattern discrimination is presented, based on the
      assumption that visual discrimination is determined by the differences in
      activity of a certain set of filters. These filters are the input units of a
      three-layer network. The units of the second layer have probabilities of
      activation that depend on the differences in activity of the input units and in
      turn they determine the probabilities of activation of a layer of output units
      from which probabilities of correct discrimination can be predicted. This model
      has been used to simulate discrete and continuous modes of curved-line
      discrimination and the results show good agreement with experimental data found
      in the literature.

PMID- 8251438
TI  - Why is the retina capable of resolving finer detail than the eye's optical and
      neural systems?
AB  - It is established that the resolving power of the eye accords with that predicted
      by diffraction theory. Campbell and Green (J. Physiol. 181, 576-593, 1965) and
      Campbell and Gubisch (J. Physiol. 186, 558-578, 1966) demonstrated that the eye
      exhibits nearly diffraction-limited performance at 2 mm pupil diameter, resolving
      up to approximately 60 cyc deg-1. However, Williams (Vision Res. 25, 195-205,
      1985) has demonstrated that foveal receptors can respond at up to 200 cyc deg-1,
      in agreement with measured receptor separation (Hirsch and Curcio, Vision Res.
      29, 1095-1101, 1989). The obvious question is: why is there such an apparent
      mismatch between the eye's optics and receptors? It is shown that the change in
      optical energy distribution corresponding to 1 just noticeable difference of
      defocus has the form of a difference of Gaussians, for which the contrast
      sensitivity function peaks at 16 cyc deg-1, with a bandwidth from 0 to
      approximately 70 cyc deg-1. The reason for the even higher-density packing of
      receptors, in the fovea, appears to be the need to allow the different colour
      response cones to be spatially inhomogeneous without excessive aliasing. Prompted
      by this analysis, some data of Williams (1985) are re-examined, leading to a
      mapping of the averaged aperture-sensitivity of foveal cones, and demonstrating
      the reason for the diffuse cutoff of the postulated defocus channel.

PMID- 8251439
TI  - Nuclease properties of two putative zinc finger peptides.
AB  - We studied the interaction of wheat germ 5S rRNA with synthetic polypeptides
      whose amino acid sequences were similar to that of the second zinc finger of
      Xenopus laevis transcriptional factor IIIA (TFIIIA). The results clearly show
      that in addition to weak 5S rRNA binding activity (data not shown), these two 30
      amino acid long polypeptides hydrolyse some phosphodiester bonds of wheat germ 5S
      rRNA. The cleavage pattern of plant 5S rRNA is very specific and the cuts occur
      only after the pyrimidine residues. The same properties of these peptides were
      furthermore observed for E. coli tRNA(Phe). We found that the digestion
      specificity of both the zinc finger peptides is very similar to that of a
      pancreatic ribonuclease (RNase A).

PMID- 8251440
TI  - Kinetics of collagen denaturation in mammalian lens capsules studied by
      differential scanning calorimetry.
AB  - Calorimetry was used to measure the rates of irreversible denaturation of
      collagen in intact mammalian lens capsules, isothermally stored in water at
      different temperatures, and the kinetic characteristics of the process
      determined. At 47.4 degrees C, the number of native collagen molecules declined
      by a factor of 10 in 21.4 +/- 2.9 min (this is called the D-value) and increasing
      the storage temperature by 2.32 +/- 0.12 degrees C reduced the D-value by a
      factor of 10. The activation energy of the process was 860 +/- 44 kJ mol-1, and
      the activation enthalpy and entropy were respectively 858 +/- 45 kJ mol-1 and
      2.38 +/- 0.14 kJ mol-1 K-1. Using equations derived in the paper, these kinetic
      characteristics were used to predict the position and shape of the denaturation
      endotherms over a range of scanning rates. Comparison of the predicted and actual
      positions of peak maxima showed a close correspondence, demonstrating that the
      principal phenomenon determining the position of the peak maxima was an
      irreversible rate process. While there was fairly good agreement between the
      predicted and actual shape of the endotherm at low scanning rates, measurements
      at high rates were distorted by the finite response time of the calorimeter, and
      the agreement was poor.

PMID- 8251441
TI  - Heat denaturation of metHb and HbNO: e.p.r. evidence for the existence of a new
      hemichrome.
AB  - Electron paramagnetic resonance was used to follow the time dependence of heat
      denaturation of met- and nitrosyl-haemoglobin (metHb and HbNO) at 60 degrees C,
      70 degrees C and 80 degrees C. The spectral changes of both complexes indicate
      that conformational changes in the protein manifest themselves in changes of the
      equilibrium of hemichromes in metHb and of six- and five-coordinated iron in
      HbNO. The formation of a hemichrome which has not been described before, with g =
      2.45, 2.27 and 1.85, is observed. A His-Fe-Cys complex is proposed for its
      structure.

PMID- 8251442
TI  - Characterization of chitosan. Influence of ionic strength and degree of
      acetylation on chain expansion.
AB  - This paper concerns a new method of characterizing chitosans with different
      degrees of acetylation (DA = 2, 11.5 and 21%); it consists of steric exclusion
      chromatography using a multidetection instrument allowing determination of M,
      [eta] and RG for each point of the chromatograms. From these data, the Mark
      Houwink parameters for intrinsic viscosity and the exponent relating RG and M are
      determined. In the same way, the role of the solvent is discussed and the solvent
      AcOH 0.3 M/AcONa 0.2 M is proposed to reduce the presence of aggregates which
      perturbs static molecular weight determination by light scattering. The role of
      the ionic concentration and of the degree of acetylation on the stiffness of
      chitosan is then discussed and a theoretical treatment is proposed allowing the
      determination of the intrinsic persistence length (Lp = 50 A) and the prediction
      of the dimensions in solution (RG and [eta]). Lp is found to be independent of DA
      in the range tested.

PMID- 8251443
TI  - Biosynthesis of poly(3-hydroxy-alkanoates) in Pseudomonas aeruginosa AO-232 from
      13C-labelled acetate and propionate.
AB  - Pseudomonas aeruginosa AO-232 produced poly(3-hydroxyalkanoates) (P(3HA))
      containing monomer units of even carbon numbers C6, C8, C10 and C12, when sodium
      acetate was fed as the sole carbon source. In contrast, the P(3HA) produced from
      sodium propionate was composed of seven different 3HA units ranging from C6 to
      C12. The pathways of P(3HA) synthesis were investigated by using 13C-labelled
      acetate and propionate as the carbon sources. The 13C-labelled carbonyl carbon of
      [1-13C] acetate was selectively incorporated into the odd-numbered carbon atoms
      of 3HA units, while the methyl carbon of [2-13C] acetate was introduced into the
      even-numbered carbon atoms of 3HA units. The 13C-labelled carbonyl carbon of [1
      13C] propionate was selectively incorporated into the third carbon atoms from
      methyl carbons in the 3HA units of C7, C9 and C11. The synthesis of P(3HA) from
      acetate or propionate was related to de novo fatty acid biosynthesis.

PMID- 8251444
TI  - Temperature-induced folding changes of beta-lactoglobulin in hydro-methanolic
      solutions.
AB  - It has been demonstrated using circular dichroism that methanol induces important
      structural changes of beta-lactoglobulin (BLG). The secondary structure of BLG
      dissolved in 45% methanol (v/v) at 30 degrees C (dielectric constant epsilon
      approximately 50) is predominantly alpha-helical and unable to complex retinol
      any more. However, when the dielectric constant of such a medium is raised back
      to epsilon approximately 70 by decreasing the temperature, both the refolding of
      BLG into a beta-structure and the formation of the retinol/BLG complex are
      observed. On the other hand, in the case of BLG solution in 30% methanol, the
      decrease of the dielectric constant from epsilon approximately 69 to epsilon
      approximately 53 by heating from 20 degrees C to 60 degrees C leads to the
      transition from a predominantly beta-structure into a predominantly random one
      and the dissociation of the retinol/BLG complex. The reversibility of the
      conformation changes by cooling was demonstrated by circular dichroism curves and
      tryptophan fluorescence. The retinol fluorescence intensity could not be
      completely recovered.

PMID- 8251445
TI  - In vitro formation and aggregation of heterotypic collagen I and III fibrils.
AB  - In vitro fibrillogenesis of solutions containing pepsin digested and acid soluble
      collagens I and III from human and bovine skin were investigated by turbidity
      time measurements, dark-field and electron microscopy. The maximum turbidity of
      these solutions exhibited inversely proportional dependence on the collagen III
      content. Self-assembly was accelerated by collagen III. As a measure of mass per
      unit length, the maximum turbidity shows a mean decrease of 88% when comparing
      the absorbance at 313 nm for 0% and 50% collagen III in a composite solution of
      acid extracted collagen. In contrast to these findings, the diameter of fibrils
      from acid extracted fetal calf skin with 50% collagen III, determined from
      electron micrographs, was only 23% smaller than for pure collagen I.
      Correspondence with investigations on in vitro fibrillogenesis with dark-field
      microscopy and electron microscopy, this phenomenon apparently derives from the
      bundling of fibrils. This may be interpreted to mean that bundling of fibrils is
      already suppressed at low collagen III concentrations. A comparison of acid and
      pepsin extracted fetal calf skin yielded similar behaviour of collagen I and III
      mixtures, even though the pepsin extract displayed a turbidity reduction that was
      about 25% less than the acid extract. For pepsin digested collagen from human and
      bovine skin, differences were found for maximum turbidity and the ability to form
      bundles decreasing with the biological age of the donor.

PMID- 8251446
TI  - Solid-state studies on synthetic fragments and analogues of elastin.
AB  - A series of synthetic fragments and analogues of elastin have been investigated,
      in the solid state, by means of differential scanning calorimetry and thermally
      stimulated current. Most of the polypeptides were shown to possess both amorphous
      regions and segments of long-range order. Water, which interacts preferentially
      with the amorphous zones, behaves as plasticizer, i.e. facilitates the localized
      motions of polypeptide chains. The results obtained have been correlated with
      elastin elasticity, in particular as far as the fundamental destructuring role of
      water is concerned.

PMID- 8251447
TI  - Improved visualization of folded collagen alpha-chains by ultra-rapid freezing.
AB  - Transmission electron microscopy techniques are commonly employed to examine the
      folded polymer structure of collagen polypeptides. These techniques include
      deposition of a sample by spraying, slow freeze-fixation, air drying and vacuum
      drying the specimen at room temperature, and using additives such as glycerol in
      the collagen preparation. Here we report preliminary observations of type I
      collagen alpha-chains, folded in water, at a concentration of 35 micrograms ml-1
      and 10 micrograms ml-1, visualized by an ultra-rapid, freeze-fixation technique
      designed to minimize structural deformation caused by spraying, additives and
      poor freeze-fixation. The technique also allows the use of submicrolitre sample
      volumes of known concentrations with negligible loss and shearing, while at the
      same time providing excellent contrast to the collagen polymer for electron
      microscopy. This technique can be employed to study the structure of a wide range
      of macromolecules (proteins and carbohydrates).

PMID- 8251448
TI  - Does the increased hydrophobicity of the interior and hydrophilicity of the
      exterior of an enzyme structure reflect its increased thermostability?
AB  - The values of hydrophobicity of internal and external elements of the secondary
      structure of three Bacillus alpha-amylase (beta alpha)8 barrel domains have been
      calculated in order to investigate whether there is some correlation between the
      values and the enzyme stability. All the values have been referred to the number
      of amino acids in the given beta-sheet or alpha-helix to eliminate the
      differences caused by non-equal length of the sheet or helix. Hydrophobicity
      units obtained have been averaged according to the number of internal (all beta
      strands and helix alpha 7) and external (helices alpha 1-alpha 6 and alpha 8)
      elements of secondary structure of the alpha-amylase (beta alpha)8 barrel. The
      averaged hydrophobicity units have been found to correlate with the thermal
      stability of the three Bacillus alpha-amylases in terms of the increased
      hydrophobicity of the interior as well as the increased hydrophilicity of the
      exterior of the (beta alpha)8 barrel domain for the alpha-amylase with increased
      thermostability.

PMID- 8251449
TI  - Fetal immunodeficiency: a consequence of placental insufficiency.
AB  - OBJECTIVE: To study the effect of placental insufficiency on fetal lymphocyte
      subpopulations. STUDY DESIGN: Cross sectional study of 19 growth retarded fetuses
      undergoing cordocentesis at 24 to 37 weeks gestation. Flow cytometry was used to
      enumerate fetal blood lymphocyte subpopulations. RESULTS: The mean T (CD3+), B
      (CD19+), T-helper (CD4+), T-suppressor/cytotoxic (CD8+) cell counts and the CD4
      to CD8 ratio in the growth retarded fetuses were significantly lower than
      respective normal mean for gestation (CD3+: z = 3.66, P < 0.001; CD19+: z = 2.18,
      P < 0.05; CD4+: z = 3.76, P < 0.001; CD8+: z = 2.26, P < 0.05; and CD4/CD8: z =
      2.27, P < 0.05). There were significant associations between the decrease in the
      T lymphocyte subpopulations and the degree of fetal acidaemia. CONCLUSIONS:
      Growth retarded fetuses demonstrate immune abnormalities that could be attributed
      to intrauterine starvation.

PMID- 8251450
TI  - Infertility treatment: from cookery to science. The epidemiology of randomised
      controlled trials.
AB  - OBJECTIVES: To review the epidemiology of published randomised controlled trials
      in infertility treatment over the last 25 years, with special emphasis on the
      number and quality of trials. DESIGN: Computer literature review by MEDLINE
      backed up by a manual search of 41 journals. Each trial was classified according
      to the methodology described and quality criteria. The results were recorded in a
      computer database. Odds ratios (OR) and confidence intervals (CI) were calculated
      where the data were sufficient. SUBJECTS: Couples suffering from primary or
      secondary infertility. The trials studied 33,761 patients overall. SETTING:
      Institute of Epidemiology and Health Services Research, Leeds. RESULTS: Five
      hundred and one randomised trials in male and female infertility treatment were
      identified between 1966 and 1990. Pregnancy was an outcome in 291 (58%) and these
      were the subject of detailed analysis. Two hundred and twenty-four (77%) and 67
      (23%) 'pregnancy trials' were concerned, respectively, with female and male
      infertility. Four per cent of the trials were preceded by a sample size
      calculation, and the average sample size was 96 patients (range 5-933); 700
      patients per group would be required to demonstrate plausible success rates for
      most treatments. The method of randomisation was unstated or pseudo-randomised in
      206 (71%) of trials where pregnancy was an outcome. Only 29 (5.8%) of studies
      were multicentre. The method of confirmation of pregnancy was omitted for 70% of
      papers. Cross-over design was used in 103 (21%) of cases. Meta-analysis is
      possible for selected topics such as the use of anti-oestrogens in idiopathic
      oligospermia and unexplained female infertility. Eight cases of double reporting
      were identified. CONCLUSIONS: Trials using randomised methodology were relatively
      few in comparison with other branches of medicine, although their use is
      important in the evaluation of treatment for infertility as treatment-independent
      pregnancy is common. It was encouraging to note that an exponential increase in
      the use of this methodology occurred during the last three years, especially in
      association with assisted conception techniques, and meta-analysis has become
      possible for selected topics. However, many trials suffer from an unrealistically
      small sample size, inappropriate use of cross-over design or pseudo
      randomisation. The trend towards properly controlled studies should be encouraged
      but these studies should be of improved quality and organised on a multicentre or
      even international basis.

PMID- 8251451
TI  - Heterotopic ectopic and intrauterine pregnancy after embryo replacement.

PMID- 8251453
TI  - Dyspareunia due to exostosis formation after pelvic fracture.

PMID- 8251452
TI  - Amniotic fluid embolism.

PMID- 8251455
TI  - Delayed haemorrhage of a persistent ectopic pregnancy following expression of
      ampullar ectopic pregnancy.

PMID- 8251454
TI  - Intra-abdominal miliary tuberculosis presenting as disseminated ovarian carcinoma
      with ascites and raised CA125.

PMID- 8251456
TI  - Symptomatic ascites complicating GnRH analogue use for myoma shrinkage.

PMID- 8251457
TI  - Amyloidosis of the uterine vessels: an unusual cause of menorrhagia.

PMID- 8251458
TI  - The use of fax machines improves out of hours labour ward management.

PMID- 8251459
TI  - Pregnancy following large loop excision of the transformation zone.

PMID- 8251460
TI  - Time to reinvent the wheel.

PMID- 8251461
TI  - Obstetric intervention and the economic imperative.

PMID- 8251462
TI  - Neural-tube defect and folic acid status in Hong Kong Chinese.

PMID- 8251463
TI  - Vaginal delivery after previous caesarean section: is X-ray pelvimetry necessary?

PMID- 8251464
TI  - The effect of pH on release of PGE2 from vaginal and endocervical preparations
      for induction of labour.

PMID- 8251465
TI  - A comparison of antenatal outcome, antenatal and intrapartum care between England
      and Wales and France.

PMID- 8251466
TI  - Routine prenatal determination of chorionicity in multiple gestation: a plea to
      the obstetrician.

PMID- 8251467
TI  - The regulation of fibroid growth: time for a re-think?

PMID- 8251468
TI  - Pain relief in labour.

PMID- 8251469
TI  - Electroencephalogram and computerised cerebral tomography findings in eclampsia.
AB  - OBJECTIVE: To define more clearly the neuropathophysiology of eclampsia. DESIGN:
      A prospective study relating to computerised cerebral tomography (CAT) scan and
      electroencephalogram (EEG) findings in eclampsia. SETTING: A large referral
      centre in a developing society. SUBJECTS: Thirty-two women with eclampsia. MAIN
      OUTCOME MEASURES: Abnormalities in EEG and CAT scan findings. RESULTS:
      Approximately 45% of the women studied had CAT scan abnormalities, while 90% had
      EEG abnormalities. A burst suppression pattern on EEG examination was found in
      four women suggesting a temporary dissolution of cerebral function to the
      midbrain level as the cause of seizures. CONCLUSIONS: EEGs are probably more
      sensitive than CAT scans in detecting the extent of the pathology in the brain in
      women with eclampsia.

PMID- 8251470
TI  - Doppler ultrasound screening as part of routine antenatal scanning: prediction of
      pre-eclampsia and intrauterine growth retardation.
AB  - OBJECTIVE: To assess the value of incorporating continuous wave Doppler
      ultrasound of the uterine arteries into the routine scan as a screening test in
      an unselected population. DESIGN: A cross sectional study by multiple operators
      using continuous wave Doppler ultrasound to obtain flow velocity waveforms (FVW)
      from both uterine arteries of all women attending for routine anomaly scan at 18
      to 22 weeks over a period of 12 months. An abnormal FVW in either uterine artery
      was used to predict intrauterine death, antepartum haemorrhage and three
      different degrees of severity of pre-eclampsia and growth retardation, singly and
      in combination. SETTING: King's College Hospital, London. SUBJECTS: Two thousand,
      four hundred and thirty women attending for routine anomaly ultrasound scan.
      RESULTS: A total of 2430 women were scanned with a 90% follow up rate. The
      results demonstrate higher sensitivities than previous studies, but with a high
      proportion of false positive tests. By including an early diastolic notch in the
      definition of an abnormal FVW the prediction of pre-eclampsia is markedly
      improved; the relative risk to a woman with an abnormal waveform of developing
      moderate or severe pre-eclampsia is increased 24-fold. Although the positive
      predictive value for babies less than the 5th centile for gestation is only 15%,
      those at risk of neonatal complications may be identified. CONCLUSION: This
      simple test can be performed at a routine visit and a group of women can be
      identified for further assessment and possible therapeutic intervention.

PMID- 8251471
TI  - Fetal intracranial haemorrhage: clinical significance of in utero
      ultrasonographic diagnosis.
AB  - OBJECTIVE: To review in utero detection of fetal intracranial haemorrhage.
      DESIGN: Retrospective survey of pregnant women presenting to the ultrasonographic
      unit in whom the diagnosis of fetal intracranial haemorrhage was reached.
      SETTING: The Chaim Sheba Medical Center in Ramat Gan, and Shaare Zedek Medical
      Center in Jerusalem; two large district general hospitals, each with 6000
      maternity patients per year. SUBJECTS: Five fetuses with gestational ages ranging
      from 26 to 36 weeks. MAIN OUTCOME MEASURES: Maternal complications, fetal
      monitoring, prenatal Doppler ultrasound studies, postnatal imaging studies,
      neonatal morbidity and mortality. RESULTS: Transabdominal sonography showed
      hyperechoic lesions in the brain parenchyma, and the lateral ventricle in three
      of five fetuses. In the remaining two fetuses, transvaginal sonography enhanced
      the visualisation of ventriculomegaly with intraventricular haemorrhage in one
      and periventricular leukomalacia was identified in the second. Three fetuses were
      appropriate for gestational age, and two were severely growth retarded. In one
      woman severe pre-eclamptic toxaemia may explain intracranial haemorrhage.
      Abnormal nonstress test and abnormal flow velocity waveforms in the umbilical and
      cerebral arteries were present in the two growth retarded fetuses, and in one who
      was appropriate for gestational age. The two growth retarded fetuses died shortly
      after birth. Of the three surviving infants, two had normal long term
      development, and one developed hydrocephalus with subsequent severe
      neurodevelopmental retardation, dying at the age of seven months. CONCLUSIONS:
      This small series shows that intracranial haemorrhage has a broad spectrum of
      manifestations with diverse prognosis. Following an antenatal diagnosis of
      intracranial haemorrhage, the obstetrician must give special consideration to
      electronic fetal heart monitoring and Doppler velocity waveforms. The prenatal
      diagnosis of intracranial haemorrhage has medico-legal implications suggesting
      that neurological outcome may not necessarily be due solely to intrapartum events
      and management.

PMID- 8251472
TI  - Monoselenophosphate: synthesis, characterization, and identity with the
      prokaryotic biological selenium donor, compound SePX.
AB  - A labile, selenium donor compound required for synthesis of selenium-dependent
      enzymes and seleno-tRNAs is formed from ATP and selenide by the SELD enzyme. This
      compound, tentatively identified as a selenophosphate [Veres, Z., Tsai, L.,
      Scholz, T. D., Politino, M., Balaban, R. S., & Stadtman, T. C. (1992) Proc. Natl.
      Acad. Sci. U.S.A. 89, 2975-2979], is indistinguishable from chemically prepared
      monoselenophosphate by 31P NMR spectroscopy and ion pairing HPLC. Furthermore,
      addition of chemically prepared monoselenophosphate caused a dose-dependent
      decrease in the amount of 75Se incorporated into tRNAs from 75SePX generated in
      situ by SELD enzyme. A procedure is described for the chemical synthesis of
      monoselenophosphate in which the readily prepared (MeO)3PSe is converted in
      quantitative yield to (TMSO)3PSe followed by complete cleavage of the latter to
      monoselenophosphate in oxygen-free aqueous buffer. The chemical properties of
      chemically synthesized monoselenophosphate are described.

PMID- 8251473
TI  - NMR structural studies of the tight complex between a trifluoromethyl ketone
      inhibitor and the 85-kDa human phospholipase A2.
AB  - Arachidonyl trifluoromethyl ketone (AACOCF3) is a slow- and tight-binding
      inhibitor of the human cytosolic phospholipase A2 (cPLA2) [Street et al. (1993)
      Biochemistry 32, 5935]. 19F and 13C NMR experiments have been carried out to
      elucidate the structure of the cPLA2.AACOCF3 complex. One mole of AACOCF3 per
      mole of enzyme is tightly bound in the active site while excess molar equivalents
      of the inhibitor associate loosely and nonspecifically with hydrophobic regions
      of the protein. Incubation of the cPLA2.AACOCF3 complex with a 10-fold molar
      excess of a structurally related inhibitor allows the slow dissociation of the
      enzyme-inhibitor complex to be followed with 19F NMR. These results establish
      that the bound inhibitor is in slow exchange with the free ligand and that
      inhibition of the cPLA2 by AACOCF3 is not due to irreversible modification of the
      protein. AACOCF3 labeled with 13C at the carbonyl position was used to determine
      the nature of the bound inhibitor species. A comparison of the 13C NMR chemical
      shift value obtained from labeled enzyme-inhibitor complex (delta c 101.0 ppm)
      with the chemical shift values obtained from model compounds suggests that the
      enzyme-bound inhibitor species is a charged hemiketal. These results are very
      similar to those obtained previously with alpha-chymotrypsin and a peptidyl
      trifluoromethyl ketone inhibitor [Liang, T.-C., & Abeles, R. H. (1987)
      Biochemistry 26, 7603] and, by analogy with the serine proteases, a structural
      model for the cPLA2.AACOCF3 complex is proposed.

PMID- 8251474
TI  - Toxityping rat brain calcium channels with omega-toxins from spider and cone
      snail venoms.
AB  - Different types of voltage-sensitive Ca2+ channels in the brain can be defined by
      specific ligands: L-type Ca2+ channels are uniquely sensitive to
      dihydropyridines, and N-type Ca2+ channels are selectively blocked by the Conus
      peptide omega-CTX-GVIA. Cloning data have revealed additional calcium channel
      types in mammalian brain for which selective ligands would be desirable. We
      describe binding experiments involving three newer ligands that block
      dihydropyridine- and omega-CTX-GVIA-resistant Ca channels: omega-Aga-IIIA and
      omega-Aga-IVA from venom of the spider Agelenopsis aperta and omega-CTX-MVIIC
      from Conus magus. [125I]omega-Aga-IVA binds with high affinity (IC50 =
      approximately 50 nM) to receptors in rat brain which may correspond to P-like
      calcium channels. A second high-affinity site (IC50 = approximately 1 nM) is
      defined by [125I]omega-CTX-MVIIC, proposed here to be on an "O"-type calcium
      channel. [125I]omega-Aga-IIIA targets homologous binding sites present on
      multiple Ca channel types. The IIIA sites overlap with the binding sites for
      [125I]omega-CTX-GVIA and [125I]omega-CTX-MVIIC. The IIIA sites do not overlap
      with the site defined by omega-Aga-IVA. Thus toxin ligands may be highly specific
      for a particular Ca channel (i.e., GVIA for the N-type channel) or exhibit
      broader specificity (i.e., omega-Aga-IIIA, which appears to bind L-, N-, P-, and
      O-type Ca2+ channels).

PMID- 8251475
TI  - Interstrand cross-linking by bizelesin produces a Watson-Crick to Hoogsteen base
      pairing transition region in d(CGTAATTACG)2.
AB  - 1H NMR analysis of the bizelesin adduct of d(CGTAATTACG)2 indicates that adenines
      six base pairs apart on opposite DNA strands are cross-linked, yielding two major
      adduct conformations differing in the central duplex region (5'AATT-3'): one
      (major product) contains an AT step wherein both adenines are syn-oriented and
      Hoogsteen base paired to thymines (5HG model); the other contains anti-oriented
      AT-step adenines that show no evidence of hydrogen bonding with pairing thymines
      (5OP model). The 5OP model consists of three conformers undergoing exchange and
      differing in the orientation of the AT-step thymines. Bizelesin's size, rigidity,
      and cross-linking properties restrict the DNA adduct's range of motion and freeze
      out DNA conformation(s) adopted during the cross-linking process. This most
      reactive DNA sequence, 5'-TAATTA-3', yields an adduct conformation (5HG)
      containing a stable region of Watson-Crick (WC) to Hoogsteen (HG) to Watson-Crick
      base-pairing transitions. While bizelesin exercises a selective effect on DNA
      conformation, it intrudes into regions of base stacking less than other Hoogsteen
      pairing-inducing drugs (e.g., echinomycin). Because of this capacity to induce
      stable Hoogsteen base pairing with only minimal distortion of base-base stacking,
      bizelesin affords an opportunity to explore this unusual DNA conformation.

PMID- 8251476
TI  - Conformation of a heptapeptide substrate bound to protein farnesyltransferase.
AB  - Protein farnesyltransferase catalyzes isoprenylation of the cysteine four
      residues from the C-terminus of several proteins including p21ras. Farnesylation
      is required for the transforming activity of Ras, and many efforts are underway
      to develop inhibitors of farnesyltransferase. We have used nuclear magnetic
      resonance spectroscopy to determine the farnesyltransferase-bound conformation of
      a heptapeptide substrate, KTKCVFM, which competes for the modification of p21Ha
      ras in an in vitro assay. Analysis of transferred nuclear Overhauser effects
      reveals that the CVFM sequence of the peptide substrate is directly involved in
      binding to the enzyme and adopts a type I beta-turn conformation in the bound
      state. The present structural information should aid in the design of more
      effective inhibitors of the enzyme and in understanding the nature of the peptide
      binding site.

PMID- 8251477
TI  - Distributions of proteins and lipids in the erythrocyte membrane.
AB  - Fluorescence digital imaging microscopy was used to characterize erythrocyte
      membrane domains. To investigate the role of specific proteins in forming lipid
      domains, erythrocyte ghosts were double-labeled with fluorescent phospholipids
      and a fluorescent label specific for band 3, the major integral membrane protein.
      Areas of enrichment, or domains, were observed for both the protein and lipid
      components. The size and enrichment of the protein and lipid domains in the
      membrane depended upon the ionic strength but not the temperature. Also, there
      was a higher correlation between the areas of band 3 and phosphatidylcholine
      enrichment than between band 3 and phosphatidylserine enrichment. This is
      consistent with band 3 playing a role in the formation of the phosphatidylcholine
      domains. Furthermore, areas of spectrin enrichment also were observed in
      immunofluorescently labeled ghosts, and the band 3 domains were found to coincide
      with the spectrin domains. Thus, the distribution of band 3 in ghosts is
      influenced by interactions with the cytoskeleton. Together, these experiments
      illustrate the type of membrane heterogeneity present in erythrocyte ghosts and
      the type of lipid and protein interactions that can affect the domains.

PMID- 8251478
TI  - Molecular dynamics simulations of asialoglycoprotein receptor ligands.
AB  - Several recent studies have implicated carbohydrates in cell adhesion,
      inflammation, clearance of glycoproteins from blood circulation, embryonic
      development, and metastasis among others. Understanding the conformation of these
      carbohydrate recognition elements and their interaction at the molecular level is
      essential for the design of oligosaccharide inhibitors/drugs. Given the
      difficulty in solving carbohydrate structures by X-ray crystallography and since
      NMR experiments give only time-averaged conformation, molecular dynamics
      simulations are well suited to determine all the accessible conformations of
      oligosaccharides. Present communication reports the simulation of some of the
      oligosaccharide ligands of asialoglycoprotein receptor for 1 ns using Biosym's
      Insight II molecular modeling package on NCI-FCRDC's Y-MP 8D/8128 supercomputer.
      Results obtained from these simulations, in addition to explaining the observed
      differences in the binding affinities of these ligands to the asialoglycoprotein
      receptor, have led to a modified model for the recognition of the
      oligosaccharides by the receptor. Accordingly, only the two terminal galactose
      residues on the 1,3-arm of the triantennary oligosaccharide (GlcNAc2Man3 core of
      the N-linked oligosaccharides with N-acetyllactosamine in beta 1,2- and beta 1,4
      linkages on the 1,3-linked core mannose) are primarily required for recognition,
      and the terminal galactose on the 1,6-arm (N-acetyllactosamine in beta 1,2
      linkage on the 1,6-linked core mannose) provides additional binding energy. It
      has been shown that the oligosaccharides studied here have significant
      flexibility and the flexibility is more around the 1,3-linkage than the 1,6
      linkage. The need for simulation for longer periods and with multiple initial
      conformations is also discussed in the present report.

PMID- 8251479
TI  - Structure of (rGGCGAGCC)2 in solution from NMR and restrained molecular dynamics.
AB  - The duplex (rGGCGAGCC)2 contains tandem G x A mismatches--a common motif in the
      secondary structures of biological RNAs. The three-dimensional structure of
      (rGGCGAGCC)2 was derived using molecular dynamics and energy minimization with
      NMR-derived restraints for 78 interproton distances (per strand), 18 hydrogen
      bonds for the six Watson-Crick G x C pairs, and 26 dihedral angles (per strand).
      The G x A mismatch structures are similar to those observed in a DNA duplex [Li,
      Y., Zon, G., & Wilson, W. D. (1991) Proc. Natl. Acad. Sci. U.S.A. 80, 26-30] and
      an RNA hairpin [Heus, H. A., & Pardi, A. (1991) Science 253, 191-193], with
      hydrogen bonds from guanine 2-amino and N3 to adenine N7 and 6-amino,
      respectively. The other G 2-amino and A 6-amino protons are within hydrogen
      bonding distance of a phosphate oxygen and 2'-oxygen, respectively. Strong
      interstrand A-A and G-G stacking is observed between the G x A mismatches. This
      contrasts with the poor stacking observed between the G x A mismatches and
      closing G x C base pairs. The stems are basically A-form with all bases in the
      anti conformation and all nonterminal sugars in the C3'-endo conformation. The
      structure rationalizes previous thermodynamic, circular dichroism, and imino
      proton NMR results and suggests tandem G x A mismatches in RNA may provide a
      contact site for tertiary interactions.

PMID- 8251480
TI  - Solute diffusion in lipid bilayer membranes: an atomic level study by molecular
      dynamics simulation.
AB  - To elucidate the mechanism of solute diffusion through lipid bilayer membranes,
      nearly 4 ns of molecular dynamics simulations of solutes in phospholipid bilayers
      was conducted. The study, the first atomic level study of solute diffusion in a
      lipid bilayer, involved four simulations of an all-atom representation of a fully
      solvated dimyristoylphosphatidylcholine (DMPC) bilayer in the L alpha phase with
      benzene molecules as solutes, totaling over 7100 atoms. These simulations agree
      with experimental evidence that the presence of small solutes does not affect
      bilayer thickness but does result in slight perturbations in the ordering of the
      hydrocarbon chains. At room temperature, the benzene molecules have essentially
      isotropic motion and rotate freely. The rate of translational diffusion varies
      with position within the bilayer and is faster in the center than near the
      zwitterionic headgroups and is in excellent agreement with experimental values
      for the diffusion of small solutes in a bilayer. These simulations have
      elucidated the mechanism of diffusion in a bilayer to be similar to the "hopping"
      mechanism found for the diffusion of gases through soft polymers. Jumps of up to
      8 A can occur in as little as 5 ps whereas average motions for that time period
      are only approximately 1.5 A. In many cases, the jumps are moderated by torsional
      changes in the hydrocarbon chains which serve as "gates" between voids through
      which the benzene molecules move. Comparison of these simulations with another
      1000-ps simulation of benzene in a pure alkane provides evidence that lipid
      bilayers should not be treated as a homogeneous bulk hydrocarbon phase.

PMID- 8251481
TI  - Alpha-helix stability and the native state of myoglobin.
AB  - Native proteins fold to form structures that contain secondary-structure regular
      patterns in the peptide backbone, such as alpha-helix, beta-structure, and turns
      with high frequency. The role of this secondary structure in stabilizing the
      native folded state is presently unclear. Alanine substitutions at helical sites
      in myoglobin show no correlation with the helical propensity of the side chains
      involved. In an effort to demonstrate a relationship between the effect of a side
      chain on stabilizing secondary structure and the native structure, we have
      carried out site-directed changes in the sequence of the helical protein sperm
      whale myoglobin. Fully buried hydrophobic side chains were exchanged for similar
      side chains at sites corresponding to midhelical positions in the native state.
      The results show a positive correlation between the alpha-helix-forming ability
      of the substituted side chain and the stability of the mutant proteins, when
      differences between the size of the side chains are taken into account. If, in
      addition, each type of amino acid substitution is averaged over different sites,
      the helix propensities of the amino acids account for much of the residual
      variation. This implies that the stability of the native state of a protein is
      coupled to that of secondary structural elements in the structure. In magnitude,
      the net contribution of propensity differences is smaller than hydrophobic
      effects, but not negligible in terms of the net free energy of unfolding.

PMID- 8251482
TI  - Cysteine scanning mutagenesis of putative helix XI in the lactose permease of
      Escherichia coli.
AB  - Using a functional lactose permease mutant devoid of Cys residues (C-less
      permease), each amino acid in putative transmembrane helix XI was individually
      replaced with Cys (from Ala347 to Ser366). Fifteen of the 20 mutants are highly
      functional and accumulate lactose to > 60% of the level achieved by C-less
      permease, and an additional three mutants, all located at the cytoplasmic end of
      the helix, exhibit lower but significant lactose accumulation. Cys replacements
      for Thr348 or Lys358 result in virtually inactive permease. Lys358, however, is
      not essential for active lactose transport but plays a role in permease folding
      or membrane insertion by interacting with Asp237. Immunoblots reveal that all
      mutant proteins are present in the membrane in amounts comparable to C-less with
      the exception of Lys358-->Cys which is hardly detectable, as expected. The
      results highlight Thr348 as a potentially important residue for further analysis.
      Finally, all active mutants were assayed after treatment with the sulfhydryl
      reagent N-ethyl-maleimide, and results range from nearly complete inhibition to
      almost 2-fold stimulation. Remarkably, all of the strongly inhibited positions
      lie on one face of helix XI. The implications of the findings for packing of
      transmembrane helices in the C-terminal half of the permease are discussed.

PMID- 8251483
TI  - 11B NMR spectroscopy of peptide boronic acid inhibitor complexes of alpha-lytic
      protease. Direct evidence for tetrahedral boron in both boron-histidine and boron
      serine adduct complexes.
AB  - We have previously shown, using 15N and 1H NMR spectroscopy, that MeOSuc-Ala-Ala
      Pro-boroPhe and certain other boronic acid inhibitors form boron-histidine
      adducts with alpha-lytic protease instead of transition-state-like tetrahedral
      boron-serine adducts as is generally supposed [Bachovchin, W. W., Wong, W. Y. L.,
      Farr-Jones, S., Shenvi, A. B., & Kettner, C. (1988) Biochemistry 27, 7689-7697].
      An X-ray crystallographic study of the MeOSuc-Ala-Ala-Pro-boroPhe complex with
      alpha-lytic protease [Bone, R., Frank, D., Kettner, C. A., & Agard, D. A. (1989)
      Biochemistry 28, 7600-7609] has confirmed the existence of the boron-histidine
      bond but has concluded that the boron atom is trigonal rather than tetrahedral.
      Here we report a 11B NMR study at 160.46 MHz of this histidine adduct complex and
      of two other complexes known to be serine adducts: alpha-lytic protease with
      MeOSuc-Ala-Ala-Pro-boroVal and chymotrypsin with MeOSucAla-Ala-Pro-boroPhe. The
      11B NMR chemical shifts demonstrate that the boron atom is tetrahedral in both
      the histidine and serine adduct complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251484
TI  - A novel exosite in the light chain of human activated protein C essential for
      interaction with blood coagulation factor Va.
AB  - Activated protein C (APC) exerts its physiologic anticoagulant role by
      proteolytic inactivation of the blood coagulation cofactors Va and VIIIa. To
      identify regions on the surface of the light chain of APC that mediate
      anticoagulant activity, 10 synthetic peptides were prepared and tested for their
      ability to inhibit APC anticoagulant activity. The synthetic peptide-(142-155)
      inhibited APC anticoagulant activity in Xa-1-stage coagulation assays in normal
      and protein S-depleted plasma with 50% inhibition at 5-25 microM peptide. In a
      system using purified clotting factors, peptide-(142-155) inhibited APC catalyzed
      inactivation of factor Va in the presence or absence of phospholipids with 50%
      inhibition at 50 microM peptide. However, peptide-(142-155) had no effect on APC
      amidolytic activity or on the reaction of APC with the serpin, recombinant
      [Arg358]-alpha 1-antitrypsin. Moreover, peptide-(142-155) inhibited factor Xa
      clotting activity in normal plasma as well as in a prothrombinase assay in the
      presence of factor Va with 50% inhibition at 5 microM and 50 microM peptide,
      respectively, under the assay conditions. The peptide had no significant effect
      on factor Xa or thrombin amidolytic activity and no effect on the clotting of
      purified fibrinogen by thrombin, suggesting that it does not directly inhibit
      these enzymes' active sites. Peptide-(142-155) was shown to bind directly to
      immobilized factor Va.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251485
TI  - Controlled formation of model homo- and heterodimer coiled coil polypeptides.
AB  - Sequence-simplified coiled coil polypeptides were synthesized and their folding
      properties characterized in order to define the role of charged border residues
      at the coiled coil interface for the controlled formation of homodimer and
      heterodimer structures. Three peptides were designed to form parallel coiled
      coils with valine and leucine occupying the hydrophobic interface positions a and
      d, respectively, of the heptad repeat abcdefg. The polypeptide designated E/K42,
      with the heptad repeat sequence VSSLESK, contained glutamate and lysine in the
      interface border positions e and g, respectively, and was designed to form a
      coiled coil homodimer at neutral pH. Two other polypeptides, designated E/E35 and
      K/K35, have the heptad repeats VSSLESE and VSSLKSK, respectively. E/E35 contains
      only glutamic acid at both e and g positions; K/K35, only lysine, E/E35 and K/K35
      were designed to form a stable coiled coil heterodimer when combined at neutral
      pH. All three polypeptides were prepared by solid-phase synthesis and purified by
      reverse-phase high-performance liquid chromatography followed by size-exclusion
      chromatography. E/K42 formed a stable dimeric coiled coil structure as determined
      by circular dichroism and size-exclusion chromatography. The alpha-helical
      content of E/K42 was highest at neutral pH and decreased at extremes of pH. The
      alpha-helical structure of E/K42 at micromolar concentrations had a Tm of 62-65
      degrees C and exhibited a concentration dependence of thermal denaturation
      consistent with dimer formation. In contrast to results with E/K42, a mixture of
      E/E35 and K/K35, but neither alone, forms alpha-helix at neutral pH.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8251486
TI  - Reconstitution of normal and hyperactivated forms of casein kinase-2 by variably
      mutated beta-subunits.
AB  - Twenty-one mutants of the noncatalytic beta-subunit of human casein kinase-2 have
      been created, expressed in Escherichia coli, and purified to homogeneity. They
      are either modified at the autophosphorylation site (mutants beta delta 1-4 and
      beta A 5,6) or bear variable deletions in their C-terminal part (mutants beta
      delta 209-215, beta delta 194-215, beta delta 181-215, beta delta 171-215, beta
      delta 150-215) or have undergone Ala substitutions for the acidic and basic
      residues which are concentrated in the sequences 55-70 and 171-180, respectively.
      All these mutants have been examined for their ability to functionally replace
      the wild type beta-subunit. All substitutions and the deletions delta 1-4, delta
      194-215, and delta 209-215 are compatible with effective binding of the catalytic
      alpha-subunit, as judged by sucrose density gradient analysis, stimulation of
      catalytic activity, and protection against thermal denaturation. Deletions delta
      171-215 and delta 150-215, however, give rise to truncated molecules which are
      unable to associate with the alpha-subunit. The intermediate deletion delta 181
      215 is still compatible with association, albeit the reconstituted holoenzyme
      exhibits an altered sedimentation coefficient. The holoenzymes reconstituted with
      substituted mutants beta A 55,57, beta A55-57, and, to a lesser extent, beta A 59
      61, beta A63,64, and beta A5,6 display a basal activity which is higher (up to 4
      fold) than that of the wild type holoenzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251487
TI  - Kinetic analysis of phospholipid exchange between
      phosphatidylcholine/taurocholate mixed micelles: effect of the acyl chain moiety
      of the micellar phosphatidylcholine.
AB  - A fluorescent assay based on concentration-dependent self-quenching of the
      fluorescent phospholipid N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)phosphatidylethanolamine was used to measure the rate of phospholipid exchange
      between taurocholate/phosphatidylcholine mixed micelles. Two NBD-labeled
      phosphatidylethanolamine probes (dilauryl and dimyristoyl) were tested in
      taurocholate/phosphatidylcholine mixed micelles prepared from phosphatidylcholine
      molecules varying in saturated chain length from 12 to 18. All combinations of
      probes and micellar phosphatidylcholines gave kinetic results that were best
      described by a transfer model in which phospholipids exchange predominantly
      through the water phase at low micellar concentrations and through transient
      micelle fusions at higher concentrations. Increasing the chain length of the
      micellar-saturated diacylphosphatidylcholine from 12 to 18 carbons resulted in a
      decrease in the overall rate of exchange by a factor of 127 for NBD-labeled
      dilaurylphosphatidylethanolamine and a factor of 2490 for NBD-labeled
      dipalmitoylphosphatidylethanolamine. The reduction in the overall rate resulted
      from decreases in both mechanisms of transfer. These results argue that the
      hydrophobicity of the lipophilic core of bile salt/phospholipid mixed micelles is
      the predominant determinant of the rate of formation of transfer-competent,
      transient micelle fusions and a major determinant of the rate of micelle to water
      phospholipid dissociation.

PMID- 8251488
TI  - Structural characterization of gangliosides from resting and endotoxin-stimulated
      murine B lymphocytes.
AB  - B lymphocytes from CBA/J mice were stimulated in splenocyte cultures for 72 h
      with various endotoxins. Bisphosphoryl lipid A from Escherichia coli had the
      highest stimulatory effect followed by LPS of Citrobacter freundii and Salmonella
      minnesota as measured by [3H]thymidine uptake. Gangliosides of stimulated B cells
      (metabolically labeled with D-[1-14C]galactose and D-[1-14C]glucosamine) and
      unlabeled gangliosides from resting B cells (prepared from spleens without
      stimulus) were analyzed by high-performance TLC, DEAE anion-exchange HPLC, and
      immunostaining procedures. Contents of ganglioside-derived sialic acids,
      quantified by HPLC as their fluorescent derivatives, decreased from stimulated to
      resident B lymphocytes in the following order: LPS S. minnesota > LPS C. freundii
      > bisphosphoryl lipid A E. coli > resting B cells. Gangliosides of resting B
      cells contained more N-glycolyl- than N-acetylneuraminic acid, whereas inverse
      ratios were found in activated cells, indicating a shift from N-glycolyl- to N
      acetylneuraminic acid due to stimulation. Furthermore, a higher
      disialoganglioside content was characteristic for activated B cells. Fast atom
      bombardment mass spectrometry was performed with permethylated mono- and
      disialoganglioside fractions of LPS S. minnesota and LPS C. freundii stimulated B
      cells. Major gangliosides were GM1a and GD1a beside minute amounts of GD1b. The
      structural heterogeneity in the gangliosides was caused by (a) N-substitution of
      the sialic acids with either acetyl or glycolyl groups, (b) variation in the long
      chain base (sphingosine, sphinganine), and (c) substitution of the ceramide
      moiety by fatty acids of different chain length and degree of unsaturation
      (C16:0, C24:0,24:1).2+ p6

PMID- 8251489
TI  - Structural study of the sugar chains of human leukocyte common antigen CD45.
AB  - The leukocyte cell surface glycoprotein CD45 is a protein tyrosine phosphatase
      and is involved in signal transduction mediated by the T cell antigen receptor.
      The asparagine-linked sugar chains were released as oligosaccharides from
      purified CD45 by hydrazinolysis. Approximately 6 mol of sugar chains was released
      from 1 mol of CD45. These sugar chains were converted to radioactive
      oligosaccharides by reduction with NaB3H4 and separated into neutral and acidic
      fractions by paper electrophoresis. All of the acidic oligosaccharides were
      converted to neutral ones by digestion with sialidase, indicating that they are
      sialyl derivatives. Binding of the sialylated oligosaccharides to an SNA-agarose
      column as well as methylation analysis revealed that the oligosaccharides have
      only alpha-2,6-linked sialic acid residues. The neutral and sialidase-treated
      acidic oligosaccharides were fractionated by serial lectin column chromatography
      followed by Bio-Gel P-4 column chromatography. Structural studies of each
      oligosaccharide by sequential exo- and endoglycosidase digestion and by
      methylation analysis revealed that CD45 contains mainly bi-, tri-, and
      tetraantennary complex-type sugar chains. About 46% of the tetraantennary complex
      type sugar chains had the poly(N-acetyllactosamine) groups and 18% of the 2,4
      branched triantennary complex-type sugar chains had the fucosyl N
      acetyllactosamine group. A portion of the bi- and 2,4-branched triantennary
      complex-type sugar chains were bisected. In addition to these sugar chains, a
      small amount of high mannose-type and hybrid-type sugar chains were detected.

PMID- 8251490
TI  - Trehalose-containing lipooligosaccharides of Mycobacterium gordonae: presence of
      a mono-O-methyltetra-O-acyltrehalose "core" and branching in the oligosaccharide
      backbone.
AB  - Past evidence has indicated that Mycobacterium gordonae, as isolated from soil
      and as an occasional opportunistic pathogen, exists as a serocomplex. We now
      demonstrate that the basis of seroreactivity and diversity is a novel series of
      alkali-labile, trehalose-containing lipooligosaccharides (LOS). The structures
      from two strains were established by per-O-methylation, partial acid hydrolysis,
      infrared and high-field NMR spectroscopy, electron-impact MS, and fast atom
      bombardment/mass spectrometry of the native lipooligosaccharides and hydrolysis
      products. The structure of the major lipooligosaccharide, LOS-I, of M. gordonae
      strain 989 was defined as 2-O-CH3-4-O-CH3CO-alpha-L-Fucp-(1-->3)- beta-D-Glcp-(1-
      >3)-2-O-CH3-alpha-L-Rhap-(1-->3)-[beta-D-Xylp++ +-(1-->2)-]- alpha-L-Rhap-(1-->3)
      beta-D-Glcp-(1-->3)-alpha-L-Rhap-(1-->3 )-6-O- CH3-alpha-D-Glcp-(1<-->1)-2,3,4,6
      tetra-O-acyl-alpha-D-Glcp, which was further glycosylated at C-3 of the terminal
      2-O-CH3-4-O-CH3CO-alpha-L-Fucp by an incompletely defined N-acyl derivative of 4
      amino-4,6-dideoxy-2,3-di-O-CH3-Galp. The structure of the major
      lipooligosaccharide, LOS-I, of a second strain of M. gordonae (strain 990) was
      defined as alpha-L-Rhap-(1-->2)-3-O-CH3-alpha-L-Rhap- (1-->3)-[beta-D-Xylp-(1-
      >2)-]-alpha-L-Rhap-(1-->3)-beta-D-G lcp- (1-->3)[beta-D-Xylp-(1-->2)-]-alpha-L
      Rhap- (1-->3)-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->3)-alpha-L-Rhap-(1--> 3)-6-O
      CH3- alpha-D-Glcp-(1<-->1)-2,3,4,6-tetra-O-acyl-alpha-D-Glcp. The other minor
      LOSs from both strains were also defined. Both families of LOSs from the two
      strains contain a novel mono-6'-O-CH3-2,3,4,6-tetra-O-acyltrehalose unit,
      representing the first example of such a unit among the LOSs isolated to date
      from mycobacteria. Also, the more polar antigenic products, LOS-I, -II', -II",
      and -III from M. gordonae 989 and LOS-I, -II, and -II' from M. gordonae 990, are
      characterized by branching of the oligosaccharide backbone, the first instance of
      sugar branching in these products. In the case of LOS-I and -III from M. gordonae
      989, the branch consists of a terminal (t)-beta-D-Xylp unit, whereas in LOS-II'
      and -II", they are (t)-3-O-CH3-beta-D-Xylp and (t)-alpha-D-Araf,
      respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8251491
TI  - Characterization of the extent of internal motions in oligosaccharides.
AB  - A detailed investigation has been undertaken on the extent and nature of
      torsional fluctuations about the glycosidic linkage of the model disaccharide Man
      alpha 1-3Man alpha 1-OMe. In particular, we sought to determine whether the three
      nuclear Overhauser effects and the two long-range heteronuclear 3JCH spin
      coupling constants measurable across the glycosidic linkage were consistent with
      a single conformation or multiple conformations about that linkage. Within
      experimental error, we have found that these five parameters can be interpreted
      in terms of a single, rigid geometry. Alternatively, the data are also consistent
      with a model in which the glycosidic torsional angles exhibit significant but
      restricted fluctuations about the global minimum energy conformation. Evidence
      from restrained molecular dynamics simulations both in vacuo and with explicit
      inclusion of solvent water and from 13C relaxation measurements upon an
      oligomannose glycan in covalent association with protein suggests that the latter
      model is the most accurate representation of the conformational behavior of
      oligosaccharides in solution.

PMID- 8251492
TI  - Evidence for orientation-conserved transfer in the TCA cycle in Saccharomyces
      cerevisiae: 13C NMR studies.
AB  - When [4-13C]glutamate is incubated with yeast cells, the [13C]aspartate formed
      shows a [2-13C]/[3-13C] ratio that is greater than 1. If the conversion occurs
      through the Krebs TCA cycle with the symmetrical intermediates succinate and
      fumarate, the ratio is expected to be 1. The addition of fluoroacetate to the
      incubation increases the ratio further. When the mutants Aco1- or CS1- are used,
      little or no aspartate is formed. When [2-13C]acetate is incubated with yeast,
      the C2-/C3-aspartate ratio is 1.5 at 2 min and decrease to 1.0 after 10 min of
      incubation. These results indicate that orientation-conserved transfer occurs at
      the succinate thiokinase and succinate dehydrogenase steps of the Krebs TCA
      cycle.

PMID- 8251493
TI  - Threonine 246 at the active site of the L-lactate dehydrogenase of Bacillus
      stearothermophilus is important for catalysis but not for substrate binding.
AB  - Threonine 246 is an active site residue that is conserved in all known L-lactate
      dehydrogenase (LDH; EC 1.1.1.27) sequences. In order to investigate the role of
      Thr246 in Bacillus stearothermophilus LDH, this residue was altered by site
      directed mutagenesis to valine, alanine, leucine, and serine, respectively. The
      effects of these mutations, as observed in both steady-state and single-turnover
      kinetic measurements with different substrates, demonstrated the importance for
      catalysis of a hydroxyl group in the 246 amino acid residue. In contrast, no
      significant contribution of the OH group of Thr246 to productive pyruvate binding
      was observed. Instead, it is proposed that the role of Thr246 may be to
      facilitate hydride transfer from the nicotinamide ring of the NADH cofactor to
      the pyruvate carbonyl group.

PMID- 8251494
TI  - Locus of action of acetyl CoA in the biotin-carboxylation reaction of pyruvate
      carboxylase.
AB  - The [14C]carboxyphospho-enzyme complex formed by incubation of the enzyme with
      H14CO3-, MgATP, and Mg2+ was prepared and isolated by gel filtration as described
      by Phillips et al. [(1992) Biochemistry 31, 9445-9450]. When time courses of
      transfer of the [14C]carboxyl group from the complex to pyruvate were studied, it
      was found that at the first time point (15 s) the formation of [14C]oxalacetate
      was the same in the presence or absence of acetyl CoA. However, in the absence of
      acetyl CoA, the radioactivity fixed in [14C]oxalacetate declined rapidly over the
      subsequent 15 min, whereas in the presence of acetyl CoA the formation of
      [14C]oxalacetate continued up to about 10 min. The decline in [14C]oxalacetate in
      the absence of acetyl CoA was found to be due to enzyme-dependent decarboxylation
      of the oxalacetate by the enzyme. Incubation of the isolated [14C]carboxyphospho
      enzyme complex with MgADP and Mg2+ resulted in no significant reduction in the
      formation of [14C]oxalacetate on addition of acetyl CoA and pyruvate. Incubation
      of the isolated [32P]carboxyphospho-enzyme complex with pyruvate resulted in no
      significant reduction in the formation of [gamma-32P]ATP on the addition of MgADP
      and Mg2+. This new evidence casts doubt on the suggested locus of activation of
      the enzyme by acetyl CoA being the facilitation of the transfer of the carboxyl
      group from carboxyphosphate to biotin and indeed on the identity of the isolated
      enzyme intermediate [Phillips et al. (1992) Biochemistry 31, 9445-9450].

PMID- 8251495
TI  - Cooperativity in the mechanism of malate dehydrogenase.
AB  - Cooperativity in the catalytic mechanism of porcine cytoplasmic malate
      dehydrogenase (sMDH) has been a point of ongoing discussion. Though previous
      investigations revealed little evidence of cooperativity, chemical modification
      studies reported by this laboratory demonstrate that binding of cofactor or
      cofactor plus substrate causes the enzyme's subunits to become chemically
      nonidentical. Therefore, we have reexamined the enzyme's steady-state kinetic and
      ligand-binding properties. To aide in characterizing sMDH kinetics, activities of
      the native enzyme and of sMDH, which was partially inactivated by an active-site
      specific reagent, were examined. As expected for a negatively cooperative enzyme,
      steady-state kinetics (at pH 8.0, the pH optimum of the enzyme) are characterized
      by concave Eadie-Hofstee plots. Further, qualitative as well as quantitative
      results from partially inactivated sMDH strongly support negative cooperativity
      and eliminate many alternative mechanisms. Finally, results from equilibrium
      binding experiments are consistent with cytoplasmic malate dehydrogenase binding
      NADH in a negatively cooperative manner. Together, these results indicate that
      cytoplasmic malate dehydrogenase acts as a negatively cooperative enzyme.

PMID- 8251496
TI  - Alternative model for mechanism-based inhibition of Escherichia coli
      ribonucleotide reductase by 2'-azido-2'-deoxyuridine 5'-diphosphate.
AB  - Ribonucleotide reductase (RDPR) from Escherichia coli is composed of two
      subunits, R1 and R2, and catalyzes the conversion of nucleotides to
      deoxynucleotides. The mechanism of inactivation of RDPR by 2'-azido-2'
      deoxynucleoside 5'-diphosphate (N3UDP) has been examined using a variety of
      isotopically labeled derivatives: (1'-, 2'-, 3'-, or 4'-[2H])-N3UDPs and 2'
      [15N3, 13C]-N3UDP. Electron paramagnetic resonance (EPR) and electron spin echo
      envelope modulation (ESEEM) spectroscopy studies using these compounds indicate
      that the 2' carbon-nitrogen bond to the azide moiety is cleaved prior to or upon
      formation of the nitrogen-centered radical derived from the azide moiety of
      N3UDP. EPR studies reveal no hyperfine interactions of the nitrogen-centered
      radical with the 1', 2', 3', or 4' hydrogens of N3UDP. ESEEM studies however,
      reveal that the 1' and 4' deuterons are 3.3 +/- 0.2 and 2.6 +/- 0.3 A,
      respectively, from the nitrogen-centered radical. Further support for carbon
      nitrogen bond cleavage is derived from studies of the interaction of oxidized R1,
      C225SR1, and C462SR1 with R2 and N3UDP. In all three cases, in contrast to the
      results with the wild type R1, azide is detected. Nitrogen-centered radical is
      not observed with either oxidized R1 or C225SR1 but is observed with C462SR1.
      These results suggest that C225 is required for the conversion of azide into N2
      and a nitrogen-centered radical. The dynamics of the inactivation of RDPR by
      N3UDP have also been examined. Use of [3'-2H]N3UDP reveals an isotope effect of
      approximately 2 on the loss of the tyrosyl radical and the rate of inactivation
      of RDPR. In both cases the kinetics are complex, suggesting multiple modes of
      inactivation. In addition, several modes of inactivation are required to explain
      the observation that loss of the tyrosyl radical is slower than the rate of
      inactivation. Studies using [5'-3H]N3UDP reveal that the rapid inactivation is
      the result of the formation of a tight noncovalent complex between modified
      nucleotide, nitrogen-centered radical and RDPR. Destruction of the nitrogen
      centered radical is a slow process which appears to be accompanied by
      decomposition of the modified nucleotide into PPi, uracil, and 2-methylene-3(2H)
      furanone. The latter covalently modifies R1 and ultimately leads to loss of
      approximately 50% of the activity of R1.

PMID- 8251497
TI  - Oxidative polypeptide cleavage mediated by EDTA-Fe covalently linked to cysteine
      residues.
AB  - Chemical cleavage with reactive oxygen species generated by EPD-Fe, a protein
      tethered EDTA-Fe reagent, has been proposed as a method to map the structure of
      nonnative equilibrium protein folding intermediates [Ermacora, M. R., Delfino, J.
      M., Cuenoud, B., Schepartz, A., & Fox, R. O. (1992) Proc. Natl. Acad. Sci. U.S.A.
      89, 6383-6387]. The chemical structure of protein cleavage products and the
      mechanism of backbone scission for this class of reagents have been unclear.
      Here, we report the nature of EPD-Fe-mediated backbone cleavage of a small model
      peptide. The EPD-Fe reagent was attached to a partially alpha-helical peptide,
      alpha 1BA1a (Ac-AEAEEAAKKAKEACKA-NH2), through a mixed disulfide. Backbone
      cleavage was initiated by addition of the iron reductant ascorbate. Chemical
      analysis of the novel cleavage products revealed an oxidative cleavage mechanism,
      probably initiated by diffusible hydroxyl radicals. The EPD-Fe-mediated cleavage
      technique appears to be suitable for the analysis of nonnative protein states
      such as the molten globule.

PMID- 8251498
TI  - Alcohol dehydrogenase-dependent reduction of 2-nitrosoflurene and rearrangement
      of N-hydroxy-2-aminofluorene.
AB  - Various C-nitroso compounds are intermediates of arylamine oxidation or
      nitroarene reduction. Reductive metabolism of C-nitroso compounds to their
      corresponding hydroxylamines is a necessary step in the activation of these
      compounds to mutagenic end points. In this study, 2-nitrosofluorene (2-NOF) has
      been investigated as an aldehyde substrate analogue for horse liver alcohol
      dehydrogenase (HLADH). The reaction products are assigned on the basis of their
      UV/visible spectra and coelution with authentic standards in reversed-phase HPLC.
      The direct product of 2-NOF reduction is N-hydroxy-2-aminofluorene (N-OH-2-AF),
      which undergoes further reduction to 2-aminofluorene (2-AF) and rearrangement to
      1- and 3-hydroxy-2-aminofluorene (1- and 3-OH-2-AF). The formation of these
      products is potently inhibited by pyrazole indicating the involvement of active
      site zinc ion in the role of a Lewis acid catalyst. It is suggested that the
      rearrangement reaction occurs via an inner-sphere N-OH 2AF-Zn2+...E-coenzyme
      complex following the elimination of the hydroxyl group from the N-OH-2-AF
      intermediate and the hydrolysis of the fluorenyl nitrenium-derived carbocations
      to yield the hydroxy 2-AF products. Herein ADH is identified as a C-nitroso
      reducing enzyme which must be considered in the mutagenic sequelae of nitro and
      nitrosoarenes.

PMID- 8251499
TI  - Characterization of a novel form of thymidylate synthase: a heterodimer isolated
      after specific chemical modification of the immobilized native enzyme.
AB  - A novel approach, utilizing covalent chromatography and selective chemical
      modification, is described for application in studying subunit interactions
      involved in the catalytic and regulatory mechanisms of certain oligomeric
      proteins. The specific objective was to prepare and characterize heterodimeric
      form of thymidylate synthase which would serve as a model for an intermediate
      stage of the catalytic mechanism in which the active-site cysteine of one subunit
      would be engaged in covalent catalysis while that of the other subunit would
      exist in the free sulfhydryl or thiolate anion form. Dimeric Lactobacillus casei
      thymidylate synthase was subjected to covalent chromatography on thiopropyl
      Sepharose 6B resin under conditions in which a mixed disulfide linkage was formed
      with the catalytic sulfhydryl group of just one of the two subunits. Specific
      chemical modification of the remaining essential sulfhydryl group of the
      immobilized group enzyme with N-ethylmalemide, followed by cleavage and elution
      with buffer containing 2-mercaptoethanol, yielded the desired soluble
      heterodimeric form of the enzyme. The specific activity of this unique form of
      the enzyme (1.55 units/mg) was approximately 60% that of native protein (2.61
      units/mg). Gel electrophoretic analysis of the heterodimeric enzyme, incubated in
      the presence of FdUMP and 5,10-methylenetetrahydrofolate (CH2H4folate), resulted
      in the appearance of a single protein band corresponding to the 1:1:1 enzyme
      FdUMP-CH2H4folate complex, confirming the new species as dimeric thymidylate
      synthase containing a single functional active site.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8251500
TI  - Mutagenic and genotoxic effects of three vinyl chloride-induced DNA lesions: 1,N6
      ethenoadenine, 3,N4-ethenocytosine, and 4-amino-5-(imidazol-2-yl)imidazole.
AB  - The mutagenic and genotoxic properties of 1,N6-ethenoadenine (epsilon Ade), 3,N4
      ethenocytosine (epsilon Cyt), and 4-amino-5-(imidazol-2-yl)imidazole (beta) were
      investigated in vivo. The former two modified bases are known DNA adducts formed
      by the human carcinogen vinyl chloride; beta is formed by pyrimidine ring-opening
      of epsilon Ade. Chemically synthesized deoxyhexanucleotides containing epsilon
      Ade and beta, d[GCT-(epsilon A)GC], and d[GCT(beta)GC], respectively, were
      described previously [Biochemistry (1987) 26, 5626-5635]. epsilon Cyt was
      inserted into an oligonucleotide, d[GCTAG(epsilon C)], by a mild enzymatic
      synthetic procedure, which avoided exposure of the base to alkaline conditions.
      3,N4-Etheno-2'-deoxycytidine 3',5'-bisphosphate coupled with reasonable
      efficiency (30-40%) to the 3'-nucleoside of an acceptor pentamer, d(GCTAG), in a
      reaction catalyzed by T4 RNA ligase in the presence of ATP. Each of the three
      modified hexanucleotides and an unmodified control were inserted into a six-base
      gap positioned at a known site in the genome of bacteriophage M13-NheI. A nick
      was placed in the DNA strand opposite that containing the single DNA lesions,
      enabling the formation of singly adducted single-stranded genomes by
      denaturation. After transfection of the adducted phage DNAs into Escherichia
      coli, each of the adducts was found to be genotoxic. The most toxic lesion was
      beta, which reduced survival of the genome by 97%. epsilon Cyt and epsilon Ade
      reduced survival by 90% and 65%, respectively. An examination of the surviving
      phage populations revealed that each of the three adducts was mutagenic. The
      least mutagenic lesion was epsilon Ade (0.1% of the survivors were mutant), which
      showed primarily A-->G transitions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251501
TI  - Mapping the central fold of tRNA2(fMet) in the P site of the Escherichia coli
      ribosome.
AB  - 4-Thiouridine (s4U), a photoreactive analog of uridine, was randomly incorporated
      into tRNA2(fMet) precursor molecules by transcription with T7 RNA polymerase. The
      s4U-containing transcripts were trimmed at their 5'-ends with RNase P RNA to
      yield mature tRNA2(fMet). The photoreactive tRNA2(fMet) derivatives were
      aminoacylated and bound to the P site of 70S ribosomes from Escherichia coli in
      the presence of a poly(A,G,U) template. Irradiation of the complexes at 300 nm
      resulted in the covalent cross-linking of tRNA2(fMet) to ribosomal proteins and
      rRNAs within both the 50S and 30S subunits. The labeled proteins were identified
      as L1, L27, and S19. 50S-subunit proteins L1 and L27 were attached to nucleotide
      U17 or U17.1 within the D loop of tRNA2(fMet), whereas 30S-subunit protein S19
      was cross-linked to nucleotide U47 in the variable loop. Both of these sites
      occur in or near the central fold of the tRNA. These results permit us to map the
      D loop of P site-bound tRNA to the region between the central protuberance and
      the L1 ridge on the 50S ribosomal subunit, while the variable loop can be placed
      above the cleft on the head of the 30S subunit.

PMID- 8251502
TI  - Ribosomal protein S17: characterization of the three-dimensional structure by 1H
      and 15N NMR.
AB  - The structure of ribosomal protein S17 from Bacillus stearothermophilus was
      investigated by two-dimensional homonuclear and heteronuclear magnetic resonance
      spectroscopy. The 1H and 15N chemical shift assignments are largely complete, and
      a preliminary structural characterization is presented. The protein consists of
      five beta-strands that form a single antiparallel beta-sheet with Greek-key
      topology. The beta-strands are connected by several extended loops, and two of
      these contain residue types that are frequently seen in the RNA-binding sites of
      proteins. Additionally, two point mutations that affect antibiotic resistance,
      translational fidelity, and ribosome assembly are located in these two regions of
      the protein. Since these potential RNA-binding sites are distributed over a large
      surface of the protein, it appears that the molecule may interact with several
      regions of 16S rRNA.

PMID- 8251503
TI  - Characterization of the two tryptophan residues of the lactose repressor from
      Escherichia coli by phosphorescence and optical detection of magnetic resonance.
AB  - The native lactose repressor from Escherichia coli (Lac Rep) and two single-point
      mutants, W220Y and W201Y, were investigated using low-temperature phosphorescence
      and optical detection of magnetic resonance (ODMR) spectroscopy. Emission from
      two tryptophan residues was evident in the phosphorescence spectrum of native Lac
      Rep at 77 K. Using the single-point mutants, the triplet-state properties of
      tryptophans 201 and 220 were obtained independently. Trp 220 was characterized as
      a partially solvent-exposed residue (0,0 band centered at 409.5 nm), while
      tryptophan 201 exhibited the properties of a buried residue (0,0 band centered at
      413.5 nm). Both single-point mutant proteins experienced changes in tryptophan
      triplet-state properties as a result of binding either of two inducer sugars:
      isopropyl beta-D-thiogalactoside, a monosaccharide, or melibiose, a disaccharide.
      Putative singlet-singlet energy transfer from tryptophan 220 to tryptophan 201
      was also investigated, but the quantitative results must be viewed with some
      caution.

PMID- 8251504
TI  - X-ray diffraction of a cysteine-containing bacteriorhodopsin mutant and its
      mercury derivative. Localization of an amino acid residue in the loop of an
      integral membrane protein.
AB  - We have used heavy-atom labeling and X-ray diffraction to localize a single amino
      acid in the integral membrane protein bacteriorhodopsin (bR). To provide a
      labeling site, we used the bR mutant, A103C, which contains a unique cysteine
      residue in the short loop between transmembrane alpha-helices C and D. The mutant
      protein was expressed in and purified from Halobacterium halobium, where it forms
      a two-dimensional crystalline lattice. In the lattice form, the protein reacted
      with the sulfhydryl-specific reagent p-chloromercuribenzoate (p-CMB) in a 1:0.9
      stoichiometry to yield the p-mercuribenzoate derivative (A103C-MB). The
      functional properties of A103C and A103C-MB, including the visible absorption
      spectrum, light-dark adaptation, photocycle, and proton release kinetics, were
      similar to those of wild-type bR. X-ray diffraction experiments demonstrated that
      A103C and A103C-MB membranes have the same hexagonal protein lattice as wild-type
      purple membrane. Thus, neither the cysteine substitution nor mercury labeling
      detectably affected bR structure or function. By using Fourier difference
      methods, the in-plane position of the mercuribenzoate label was calculated from
      intensity differences in the X-ray diffraction patterns of A103C and A103C-MB.
      This analysis revealed a well-defined mercury peak located between alpha-helices
      C and D. The approach reported here offers promise for refining the bR structural
      model, for monitoring conformational changes in bR photointermediates, and for
      studying the structure of other proteins in two-dimensional crystals.

PMID- 8251505
TI  - Phosphorylation of ribonucleotide reductase R2 protein: in vivo and in vitro
      evidence of a role for p34cdc2 and CDK2 protein kinases.
AB  - Ribonucleotide reductase is responsible for supplying the deoxyribonucleotides
      required for DNA synthesis and repair. The active enzyme consists of two
      dissimilar protein components called R1 and R2. Immunoprecipitation of R1 and R2
      proteins from [32P]orthophosphate-labeled exponentially growing mouse L cells
      showed that the R2 protein but not the R1 protein of ribonucleotide reductase
      could be phosphorylated in vivo. Two-dimensional phosphopeptide mapping
      experiments of trypsin-digested R2 protein showed a major spot containing more
      than 90% of the total radioactivity and a minor spot with the remaining
      radioactivity. Phosphoamino acid analysis of R2 phosphorylated protein indicated
      that phosphorylation occurred exclusively on serine. Protein kinase C, cAMP
      dependent protein kinase, p34cdc2, and CDK2 were capable of phosphorylating the
      R2 protein in vitro, whereas casein kinase II was not. To determine whether any
      of these enzymes could phosphorylate peptides observed to be phosphorylated in
      actively growing cells, tryptic phosphopeptide maps of R2 that had been
      phosphorylated in vitro were compared with maps of R2 that had been isolated from
      [32P]-labeled cells. Only the phosphopeptide maps obtained with p34cdc2 and CDK2
      matched the pattern found in [32P]-labeled cells. Experiments in which tryptic
      digests from different samples were mixed prior to two-dimensional separation
      demonstrated comigration of phosphopeptides obtained by in vivo phosphorylation
      with phosphopeptides derived from p34cdc2 or CDK2 obtained by in vitro
      phosphorylations. These studies indicate that protein R2 phosphorylation may play
      an important role in the regulation of ribonucleotide reduction, DNA synthesis,
      and cell cycle progression, and suggest a potentially important p34cdc2 and/or
      CDK2 regulation point in DNA replication.

PMID- 8251506
TI  - Binding of transformed Ah receptor complex to a dioxin responsive transcriptional
      enhancer: evidence for two distinct heteromeric DNA-binding forms.
AB  - Guinea pig hepatic Ah receptor (AhR) complex was transformed in vitro to its DNA
      binding form by incubation with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD,
      dioxin). Transformed TCDD-AhR was covalently cross-linked by UV-irradiation to a
      bromodeoxyuridine-substituted oligonucleotide containing its specific DNA
      recognition site, the dioxin responsive element (DRE). Denaturing gel
      electrophoresis and autoradiography identified four TCDD-inducible protein-DNA
      complexes, with molecular masses of approximately 97, 105, and 115 kDa and a
      somewhat broader complex at 247 kDa. The 247-kDa complex appears to contain two
      distinct protein-DNA complexes of approximately 232 and 256 kDa and represents
      two proteins covalently cross-linked to a single DRE oligonucleotide, while the
      97, 105, and 115-kDa complexes represent single protein-DRE cross-links. UV cross
      linking to DRE oligonucleotides containing variable numbers of BrdU residues
      revealed that the 105-kDa protein, identified as the AhR ligand-binding subunit
      by photoaffinity labeling with a radioiodinated AhR agonist, cross-links to the
      DRE core consensus (5'-GCGTG-3'); the 97- and 115-kDa non-ligand-binding proteins
      differentially cross-link immediately 5'-ward of the core. Overall, our results
      not only demonstrate that the critical protein-DNA contacts which occur between
      the AhR complex and the DRE are made primarily by the ligand-binding subunit but
      also indicate that the AhR complex exists as two distinct heteromeric DNA-binding
      forms, containing one 105-kDa ligand-binding subunit and either one 115- or one
      97-kDa non-ligand-binding subunit.

PMID- 8251507
TI  - Cytosine methylation enhances mitomycin C cross-linking.
AB  - Mitomycin C (MC) is a powerful antitumor agent that targets the DNA sequence CpG.
      Because it is likely that this dinucleotide will contain 5-methylcytosine in
      vivo, we have compared the cross-linking efficiency of MC for DNA containing
      either 5-methylcytosine or normal cytosine embedded in random-sequence DNA
      oligomers. We have found that mitomycin C displays a small but significant
      preference for methylated DNA. Recognition of an abnormal methylation pattern in
      the DNA of transformed cells may therefore be one mechanism by which MC exerts
      its chemotherapeutic effects.

PMID- 8251508
TI  - Molecular dynamics simulations provide a structural basis for the experimentally
      observed nucleotide preferences for DNA interstrand cross-links induced by
      aziridinylbenzoquinones.
AB  - Two-electron reduction of the structurally related aziridinylbenzoquinones DZQ
      and MeDZQ to their hydroquinone forms, DZHQ and MeDZHQ, respectively, generates
      species which interact and cross-link DNA at distinct nucleotide sequences.
      Within single target site duplex oligonucleotides, DZHQ was found to cross-link
      DNA at 5'-GC-3' and 5'-GNNC-3' sequences, whereas MeDZHQ was found to cross-link
      predominantly at 5'-GNC-3' within a 5'-GTCA-3' sequence. In a multitarget site
      duplex oligonucleotide, which contains either the target sequence 5'-TGCAC-3' or
      5'-TGCTC-3', DZHQ was found to cross-link at both a 5'-GC-3' (a 1,2 cross-link)
      and a 5'-GNNC-3' (a 1,4 cross-link) site with approximately equal efficiency.
      Molecular dynamics simulations were able to accurately reproduce the experimental
      results and provide a structural basis for the alkylation preferences.
      Calculations were performed to determine the mobility of the hydroquinone species
      following guanine N7 (G) alkylation at 5'-TGCAC-3' and 5'-TGTCA-3' sequences.
      Conformations consistent with the formation of both 1,2 and 1,4 cross-links were
      observed when DZHQ was placed within a 5-TGCAC-3' sequence. The 1,2 cross-link
      orientation was more stable and thermodynamically favored. For MeDZHQ at the same
      site the ligand was unable to form stable 1,2 or 1,4 cross-linking conformations,
      primarily due to clashes with thymine methyl groups. In contrast, the MeDZHQ
      monoadduct with a 5'-TGTCA-3' sequence adopted a very stable conformation
      consistent with formation of a 1,3 cross-link.

PMID- 8251509
TI  - Mechanism for the rotamase activity of FK506 binding protein from molecular
      dynamics simulations.
AB  - Molecular dynamics (MD) and free energy perturbation (FEP) methods are used to
      study the binding and mechanism of isomerization of a tetrapeptide (AcAAPFNMe) by
      FK506 binding protein (FKBP). Detailed structures are predicted for the complexes
      of FKBP with the peptide in both ground-state and transition-state forms. The
      results support a mechanism of catalysis by distortion, where a large number of
      nonbonded interactions act together to stabilize preferentially the twisted
      transition state. The two most important groups for the catalysis are suggested
      to be Trp59 and Asp37, but several other groups are identified as directly or
      indirectly involved in the binding and catalysis. However, the structural results
      do not support the notion that the keto oxygen of the immunosuppressive agents
      FK506 and rapamycin mimics the oxygen for the twisted peptide bond in the FKBP
      transition-state complex.

PMID- 8251510
TI  - Structure, spectroscopic, and redox properties of Rhodobacter sphaeroides
      reaction centers bearing point mutations near the primary electron donor.
AB  - Single mutations of three amino acid residues in the vicinity of the primary
      electron donor, P, in the reaction center (RC) from Rhodobacter (Rb.) sphaeroides
      were constructed and characterized in order to study the effects of hydrogen
      bonding on the physical properties of P. The mutations, Phe M197-->Tyr, Met L248-
      >Thr, and Ser L244-->Gly, represent single amino acid changes near P designed to
      introduce residues found in Rhodopseudomonas (Rps.) viridis and to, thus, probe
      the effects of nonconserved residues. The mutations were designed to change the
      nonconserved H-bonding interactions of P in Rb. sphaeroides, at the level of a C2
      acetyl, a C9 keto, and a C10 ester carbonyl of P, respectively, to those present
      in Rps. viridis. The Fourier transform (pre)resonance Raman (FTRR) spectra of P,
      in its reduced and oxidized states, from reaction centers of these mutants were
      studied to determine modifications of H-bond interactions of the pi-conjugated C2
      acetyl and C9 keto carbonyl groups and the C10 carbomethoxy ester carbonyl groups
      of P. The vibrational spectra of reduced P in the Met L248-->Thr and Ser L244-
      >Gly mutants reveal no evidence for changes in the H-bonding pattern of P; this
      suggests that for Rb. sphaeroides wild type, Ser L244 is not H-bonded to the C10
      ester carbonyl of PL. The vibrational spectrum of reduced P from the Phe M197-
      >Tyr mutant compared to that of wild type can unambiguously be interpreted in
      terms of the formation of a new H-bond with an acetyl carbonyl of P, specifically
      PM. Correlating with the new H-bond, the Phe M197-->Tyr mutant exhibits an
      electronic absorption spectrum where the P absorption band is significantly
      perturbed. Intact cell and chromatophore photobleaching spectra of the same
      mutant indicate that the P absorption band has red-shifted by ca. 10 nm; no such
      behavior is observed for the other mutants. As well, the P-->BPheL electron
      transfer rate does not seem to strongly depend on the H-bonding of the C2 acetyl
      carbonyl of PM to a tyrosine residue. The EPR zero-field splitting parameters, E
      and D, of the primary donor triplet are only slightly modified in the mutant
      reaction centers, on the order of 1%.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8251511
TI  - Electron self-exchange in high-potential iron-sulfur proteins. Characterization
      of protein I from Ectothiorhodospira vacuolata.
AB  - During previous research on oxidized and reduced high-potential iron-sulfur
      proteins (HiPIP hereafter), qualitative different electron self-exchange rates
      were noticed. We have now investigated this phenomenon in detail for HiPIP I and
      II from Ectothiorhodospira vacuolata, which differ significantly in total charge
      and in which the sequence homology is the largest among all known HiPIPs. We have
      also characterized the electronic structure of HiPIP I through 1H NMR and EPR
      spectroscopies to parallel the existing characterization of HiPIP II and other
      HiPIPs. This investigation has allowed us to propose a model, according to which
      the productive collisions for electron transfer occur through a hydrophobic patch
      near the cluster. The effects of total charge and redox potential are considered.
      The possible formation of dimers through the hydrophobic patch at liquid helium
      temperature is discussed in light of the EPR spectra.

PMID- 8251512
TI  - Halocyanin, an archaebacterial blue copper protein (type I) from Natronobacterium
      pharaonis.
AB  - A small blue copper protein with a molecular mass of about 15.5 kDa has been
      isolated from the haloalkaliphilic Natronobacterium pharaonis. This protein,
      which was named halocyanin, contains one Cu2+. The circular dichroism spectrum in
      the region of the absorption of the peptide bond reveals mainly beta-structural
      elements. The absorption spectrum in the visible range has three maxima with the
      main band at 600 nm. The circular dichroism spectrum in this region is
      characterized by four extrema with maxima at 413 and 590 nm and minima at 477 nm
      as well as 721 nm. The electron paramagnetic resonance spectrum displays a
      hyperfine structure which shows a close resemblance to those of plastocyanin. The
      cumulative spectral data agree well with those of other small blue copper
      proteins with axial symmetry of the Cu ligands. In analogy, one can deduce that
      halocyanin may adopt a type I copper binding site with two His, one Met, and one
      Cys as probable ligands. This conclusion is confirmed by the C-terminal sequence
      which contains, homologous to other known sequences of type I copper proteins,
      three of the four copper ligands. Halocyanin can only be removed from the
      membrane by mild treatment with detergents. This observation indicates that
      halocyanin is a peripheral membrane protein which serves as a mobile electron
      carrier. The presence of type I blue copper proteins is archaebacteria might lead
      to further insights into their phylogenetic origin.

PMID- 8251513
TI  - Modulation of the helical stability of a model peptide by ionic residues.
AB  - The mean residue ellipticity of the helical host peptide, acetyl
      YEAAAKEAXAKEAAAKA-amide containing guest residues at position X, was measured as
      a function of pH and ionic strength at 0 degree C. Changes in ellipticity at 222
      nm were interpreted in terms of a two-state helix/coil transition of a monomeric
      peptide. Variable pH measurements in low concentrations of KCl defined changes in
      helix stability resulting from the ionization of each guest residue. Variable
      [KCl] measurements at fixed pH generated ellipticity values for the neutral and
      ionic forms of each guest residue free of electrostatic and lyotropic
      contributions. These ellipticity values were used to calculate a helix
      propagation parameter for each form of a guest residue using the Lifson-Roig
      algorithm and assuming a universal nucleation parameter. In all cases, the
      propagation parameter of a residue is either unaffected or decreased by
      ionization of its side chain.

PMID- 8251514
TI  - Thermodynamic analysis of the chemotactic protein from Escherichia coli, CheY.
AB  - CheY, the 129 amino acid chemotactic protein from Escherichia coli, is a good
      model for studies of folding of parallel alpha/beta proteins. We report here the
      thermodynamic characterization of the wild-type CheY at different pH values and
      in different buffers and denaturation conditions. The denaturation of CheY by
      urea monitored by circular dichroism and fluorescence fits the two-state
      unfolding model. The stability of the protein is ionic strength dependent,
      probably due to the presence of three Asp residues in very close proximity in its
      active site. The presence of a Mg2+ ion, which seems to interact with Asp 13 in
      the active site, stabilizes the native structure by up to 6.9 kJ mol-1. The CheY
      maximum stability (31.7 +/- 2.1 kJ mol-1), without magnesium, is reached at pH
      5.1. Analysis of scanning calorimetry data has shown that temperature-induced
      unfolding of CheY is not a two-state process and proceeds through a highly
      populated intermediate state, corresponding to protein dimers, as was
      subsequently confirmed by direct cross-linking experiments. According to circular
      dichroism, fluorescence, nuclear magnetic resonance, and ANS binding experiments,
      this "intermediate dimer" at pH 2.5 exhibits all known characteristics of the
      "molten globule" state. The reversible dimerization of "molten globules" might
      explain such peculiarities as the increased stability or the cooperative
      unfolding found for the molten globule state of some proteins.

PMID- 8251515
TI  - Partitioning the effects of changes in a protein to the folded or unfolded forms
      by using a thermodynamic cycle: a change in Escherichia coli thioredoxin does not
      affect the unfolded state.
AB  - Previously, we have introduced a method whereby novel disulfide side chains can
      be produced in the interior of a protein by modifying a cysteine residue after
      denaturant-induced unfolding [Wynn, R., & Richards, F. M. (1993) Proteins:
      Struct., Funct., Genet. 2, 395-403]. Here the disulfide exchange equilibrium
      constant, Kred, between the protein C32S,C35S-L78C thioredoxin and 2-hydroxyethyl
      disulfide is studied as a function of urea concentration. Since the disulfide
      exchange reaction and the stability of the proteins are thermodynamically linked,
      independent knowledge of the stabilities of the modified and unmodified proteins
      along with measurements of Kred allows us to assign Kred values for the folded
      and urea-unfolded forms of the protein. We find that the disulfide exchange
      reaction is more favorable for the folded protein, in agreement with the
      increased stability of the modified protein, and that the Kred values for both
      states are independent of the urea concentration. Finally, Kred values for the
      unfolded protein are the same, within experimental error, as that for N
      acetylcysteine methylamide, an analog of cysteine in a peptide chain without the
      possibility of intramolecular interactions. Thus, we conclude that modification
      of position 78 of thioredoxin does not affect the unfolded state. The relevance
      of these results toward protein stability studies is discussed.

PMID- 8251516
TI  - Quinoline oxidoreductase from Pseudomonas putida 86: an improved purification
      procedure and electron paramagnetic resonance spectroscopy.
AB  - Quinoline oxidoreductase, an iron-sulfur molybdenum flavoprotein containing
      flavin adenine dinucleotide and molybdopterin cytosine dinucleotide, was purified
      from Pseudomonas putida 86 to homogeneity. The various electron-transfer centers
      of the purified enzyme were examined by electron paramagnetic resonance
      spectroscopy. Quinoline deuterated at position 2 was prepared by
      deuterodecarboxylation of 2-quinolinecarboxylic acid. Quinoline added to the
      enzyme elicited the Mo(V) "rapid" type Q signal arising from the complex of
      enzyme and substrate, whereas in oxidized quinoline oxidoreductase a Mo(V)
      "resting" signal was observed. EPR spectroscopy at helium temperatures below 70 K
      revealed the existence of two types of iron-sulfur centers, Fe-S I and Fe-S II.
      An organic free radical appeared upon reduction with sodium dithionite.
      Inactivation of the enzyme by cyanide led to the inactive desulfo quinoline
      oxidoreductase, which yielded another Mo(V) signal designated "slow" type Q upon
      reduction with dithionite. Desulfo quinoline oxidoreductase was partially
      reactivated by incubation with sulfide.

PMID- 8251517
TI  - Membrane topology of bovine adrenocortical cytochrome P-450C21: structural
      studies by trypsin digestion in vesicle membranes.
AB  - Purified adrenocortical microsomal P-450C21 was incorporated into vesicle
      membranes composed of phosphatidylcholine, phosphatidylethanolamine, and
      phosphatidylserine at a molar ratio of 5:3:1. Trypsinolysis of the incorporated P
      450C21 resulted in the formation of 30-, 25-, and 20-kDa fragments. Similar
      fragment formation was observed by trypsinolysis of bovine adrenocortical
      microsomes with Western blotting using anti-P-450C21 IgG. In the detergent
      solubilized state, trypsin cleaved P-450C21 into very small peptides. Washing of
      the trypsin-treated vesicles with 500 mM Na2CO3 failed to cause these fragments
      to separate from membranes. N-Terminal amino acid sequencing of these fragments
      showed that trypsin cleaved the 267 Arg-268Val and 332Arg-333Val bonds of P
      450C21. The time course of fragment formation indicated that trypsin cleaved the
      267Arg-268Val bond first to produce 30- and 25-kDa fragments and subsequently the
      332Arg-333Val bond in the 25-kDa fragment to produce the 20-kDa fragment. Neither
      21-hydroxylase activity, the reduced CO difference spectrum, nor the EPR spectrum
      of digested P-450C21 differed from those of undigested P-450C21. Heat treatment
      at 50 degrees C for 20 min did not cause any decrease in activity of digested P
      450C21, when the substrate progesterone was present. This high stability toward
      heat treatment was not observed in the solubilized state. Rotational diffusion
      experiments on P-450C21 showed that the size of the molecule holding the heme was
      not changed significantly after digestion. On the basis of these results, P
      450C21 is concluded to be deeply embedded in the vesicle membranes.

PMID- 8251518
TI  - Two-dimensional transferred nuclear Overhauser effect spectroscopy (TRNOESY)
      studies of nucleotide conformations in creatine kinase complexes: effects due to
      weak nonspecific binding.
AB  - The conformations of the adenosine moiety of MgADP and MgATP bound to rabbit
      muscle creatine kinase were investigated by two-dimensional transferred nuclear
      Overhauser effect spectroscopy (TRNOESY). The effects arising from adventitious
      binding of the ligands to the enzyme on the measurements were delineated. It was
      shown that, with sample protocols typically used thus far with the TRNOE method
      (enzyme, approximately 1 mM; ligand, approximately 10 mM), the TRNOESY pattern
      for the nucleotides with creatine kinase is similar to that with gamma-globulin
      and bovine serum albumin, which do not have specific nucleotide binding site(s).
      Measurements of NOE between the H1'-H2' proton pair as a function of ligand
      concentrations with the enzyme-ligand ratio kept constant at 1:10 showed that,
      for ligand concentrations over about 3-4 mM, weak nonspecific binding makes a
      significant contribution to the observed NOE. Thus the NOE values relevant for
      the determination of the nucleotide conformation at the active site were measured
      at nucleotide concentrations of about 1.5 mM. The TRNOE buildup curves for all
      the ligand-proton pairs were analyzed using a complete relaxation matrix
      approach. The interproton distances derived from the NOE's were then used as
      constraints in elucidating the ligand structure by using the program CHARMm. The
      NOE-determined structures of both MgADP and MgATP bound to creatine kinase
      correspond to an anti conformation with the glycosidic angle (O'4-C'1-N9-C8) chi
      = 51 +/- 5 degrees. The ribose pucker nominally representative of these data is a
      O4'T with a phase angle of pseudorotation (p) of 70.5 degrees.

PMID- 8251519
TI  - Conformation of a cyclic opioid peptide analog by NMR and molecular dynamics
      simulation.
AB  - The conformation of a new Ty-c[Lys-Phe-Asp]-NH2 cyclic opioid peptide synthesized
      by solid phase method, has been determined from two-dimensional NMR and distance
      geometry followed by restrained molecular dynamics simulation. The conformation
      of the ring is well-defined, but the exocylic Tyr-1 and Phe-3 side-chain moiety
      possesses significant orientational freedom.

PMID- 8251520
TI  - Structural characterization of the N-linked carbohydrate chains from mouse zona
      pellucida glycoproteins ZP2 and ZP3.
AB  - N-linked oligosaccharides of mouse zona pellucida glycoproteins ZP2 and ZP3 were
      prepared as pyridylaminated derivatives. Anion-exchange HPLC revealed that 95% or
      more of them are acidic. About 80% of these acidic chains were neutralized by
      digestion with Arthrobacter ureafaciens sialidase and a small amount of sulfate
      was found in the residual acidic chains. The neutralized fractions (SN fractions)
      from ZP2 and ZP3 were similarly fractionated by size-fractionation HPLC into many
      peaks having different numbers of LacNAc in the non-reducing regions. The SN
      fractions from ZP2 were cleaved by endo-beta-galactosidase into the core and non
      reducing regions. The tri- and tetra-antennary complex-type chains with a Fuc
      residue were predominant in the core region. On the other hand, four kinds of
      fragment containing the LacNAc sequence were obtained from the non-reducing
      region. Sialic acids were shown to be linked to the core fragments, as well as
      the non-reducing fragments. The N-linked oligosaccharides of ZP3 were suggested
      to have essentially the same structures as those of ZP2.

PMID- 8251521
TI  - Characterization of two P-450 isozymes placed in the rat CYP2D subfamily.
AB  - Two P-450s with debrisoquine 4-hydroxylation activity, designated P-450 UT-7 and
      UT-7b, were purified and partially purified, respectively, from hepatic
      microsomes of untreated male rats. Both purified P-450s with an apparent
      molecular weight of 49,000, were associated with another protein with an apparent
      molecular weight of 29,000 which was designated 29 k-protein. The CO-reduced
      spectra of both P-450 UT-7 and UT-7b showed a peak at 448 nm. The NH2-terminal
      amino acid sequences of P-450 UT-7 and UT-7b were the same as the amino acid
      sequences of CYP2D1 and CYP2D2 deduced from the cDNA, respectively, except for
      the lack of a terminal methionine for P-450 UT-7b. In a reconstituted systems, P
      450 UT-7 and UT-7b catalyzed lidocaine 3-hydroxylation and N-deethylation in the
      presence of the 29 k-protein. The Km and Vmax values for lidocaine 3
      hydroxylation were 3.6 microM and 0.50 nmol/min/nmol of P-450 for P-450 UT-7, and
      3.6 microM and 0.93 nmol/min/nmol of P-450 for P-450 UT-7b, respectively.
      Antibody against P-450 UT-7, which also cross-reacted with P-450 UT-7b, inhibited
      lidocaine 3-hydroxylation in liver microsomes from untreated male rats, but had
      little effect on lidocaine N-deethylation. These findings suggested that
      lidocaine 3-hydroxylation in hepatic microsomes from untreated male rats was
      catalyzed by P-450 UT-7 and/or UT-7b.P-450 UT-7 not containing 29 k-protein was
      obtained as the non-absorbed fraction from hydroxylapatite HPLC. The activities
      of debrisoquine 4-hydroxylation as well as lidocaine 3-hydroxylation and N
      deethylation in a reconstituted system with P-450 UT-7 without 29 k-protein were
      one-fifth of those of P-450 UT-7 containing 29 k-protein at the same substrate
      concentration. These findings suggested that the 29 k-protein was essential to
      express the maximal metabolic activities. However, the lidocaine metabolic
      activity in a reconstituted system with P-450 UT-7 containing 29 k-protein and in
      hepatic microsomes were not inhibited by 29 k-protein antibody.

PMID- 8251522
TI  - Purification and properties of a 'cytochrome a1'-like hemoprotein from a
      magnetotactic bacterium, Aquaspirillum magnetotacticum.
AB  - A novel hemoprotein was purified from a magnetotactic bacterium, Aquaspirillum
      magnetotacticum MS-1. The protein showed absorption peaks at 437 nm in the
      oxidized form, and 592, 550 and 450 nm in the reduced form. Although the spectral
      properties of the hemoprotein were very similar to those of 'cytochrome a1', the
      hemoprotein contained no molecules of heme a. The protein contained two kinds of
      hemes; one was extracted with HCl-acetone and the other was covalently bound to
      the protein. The pyridine ferrohemochrome of the former heme showed absorption
      peaks at 440, 545 and 585 nm. The chromatographic behavior of the heme on reverse
      phase HPLC was different from that of heme a. The pyridine ferrohemochrome of the
      covalently bound heme showed an alpha peak at 565 nm. On the basis of the iron
      analysis, the hemoprotein contained one molecule of each of the two kinds of heme
      in the holoprotein. The protein was composed of two kinds of subunit with
      molecular weights of 41,000 and 17,000 and showed very little cytochrome c
      oxidase activity. The amounts of the hemoprotein in the magnetic cells of A.
      magnetotacticum were larger than those in non-magnetic cells. These results
      suggest that the 'cytochrome a1'-like hemoprotein is not the terminal oxidase of
      the bacterium and may be related to the formation of magnetosome in the magnetic
      cells of A. magnetotacticum.

PMID- 8251523
TI  - Biodistribution of calcitonin encapsulated in liposomes in mice with particular
      reference to the central nervous system.
AB  - The biodistribution of [125I]porcine calcitonin (pCT) encapsulated in reverse
      phase evaporation vesicles (REVs) in mice upon the intravenous administration was
      examined. It was found that sulfatide significantly improved the stability of
      REVs in vivo, and altered the relative distribution of [125I]pCT encapsulated in
      liposomes in mice. These sulfatide-containing REVs were able to target [125I]pCT
      into the liver and central nervous system (CNS) reasonably well, with the maximal
      effect of about 40% and 2% of the injected doses occurring at 30 min and 90 min,
      respectively, after injection. Neither free [125I]pCT, nor sulfatide-free
      liposome-encapsulated [125I]pCT, nor a mixture of free [125I]pCT and empty
      sulfatide liposomes was effective. [125I]pCT was widely distributed in the CNS,
      with predominance in hypothalamus, brainstem, striatum and spinal cord. The
      results indicate that pCT encapsulated in sulfatide-containing liposomes is able
      to pass through the blood-brain barrier (BBB), and calcitonin, thus encapsulated,
      may be applicable to studies on its functions in the CNS.

PMID- 8251524
TI  - Novel inhibitors of poly(ADP-ribose) glycohydrolase.
AB  - The inhibitory effects on poly(ADP-ribose) glycohydrolase purified from human
      placenta of three classes of chemically defined tannins; gallotannins,
      ellagitannins and condensed tannins, were examined in vitro. Oligomeric
      ellagitannins were found to be most potent inhibitors of poly(ADP-ribose)
      glycohydrolase, their potencies increasing with increasing number of monomeric
      residues (dimer < trimer < tetramer). Monomeric ellagitannins and gallotannins
      were less inhibitory. Condensed tannins, which consist of an epicatechin gallate
      oligomer without a glucose core, were not appreciably inhibitory. A structure
      activity study showed that higher-order conformations of the conjugates with
      glucose of hexahydroxydiphenoyl and valoneoyl groups, which are unique components
      of ellagitannins, cooperatively potentiated the inhibitory activity.

PMID- 8251525
TI  - 31P-NMR study of transient ischemia in rat hippocampal slices in vitro.
AB  - Intracellular high energy phosphates (HEP) were monitored in rat hippocampal
      slices in vitro by 31P-NMR during continuous superfusion, no flow and reperfusion
      in order to model the changes which occur during cerebral ischemia and
      reperfusion in vivo. With continuous superfusion, stable intracellular HEP
      resonance signals were observed for over 4 h. When superfusion was stopped, there
      were rapid decreases in pH and phosphocreatine levels followed by slower loss of
      ATP. These changes are similar to those observed during cerebral ischemia in vivo
      by 31P-NMR. Upon reperfusion, the pH returned to normal, but the extent of HEP
      recovery depended on the length of time superfusion was halted. Following a 10
      min ischemic period HEP levels returned to greater than 90% of preischemic
      values, while following a 16 min ischemic period there was only 60% recovery.
      Superfusion with low calcium, high magnesium medium significantly improved the
      recovery of HEP following 16 min of ischemia to 80% of preischemic levels. These
      data support the hypothesis that calcium influx during and following ischemia can
      disrupt energy metabolism in the hippocampus, and that magnesium can have a
      protective action on cellular energy status, perhaps by further blocking calcium
      influx.

PMID- 8251526
TI  - The contribution of intermolecular hydrogen bonding to the kinetic specificity of
      papain.
AB  - The binding of substrates to the active site of papain is thought to involve,
      among other things, intermolecular P1NH-OC(Asp158) and P2NH-OC(Gly66) hydrogen
      bonding. In this study the contribution of these two putative hydrogen bonds to
      the interaction specificity of papain was measured for pairs of ligands in which
      the amide NH in question was either intact or replaced by an ester O linkage. The
      probe ligands investigated comprised substrates (peptidyl p-nitroanilides),
      substrate-like transition state analog inhibitors (peptidyl nitriles) and
      substrate-like affinity labeling agents (peptidyl Michael acceptors). Observed
      differences in interaction energies (delta delta G(obs) or delta delta G(obs) not
      equal to) for amide/ester ligand pairs indicated an apparent specificity energy
      of 2.1-2.6 kcal/mol for the P2NH-OC(Gly66) bond. For the P1NH-OC(Asp158) bond
      delta delta G(obs) was approx. 1.0 kcal/mol for dipeptidyl ligands but close to
      zero for ligands lacking a P2NH donor. These specificity energies are comparable
      to values reported for other enzyme-ligand systems. However, the dependence of
      delta delta G(obs) for the P1NH-OC(Asp158) bond on the presence of a P2NH donor
      suggests that these two hydrogen bonds may interact cooperatively in ligand
      binding. A thermodynamic cycle approach was used to relate delta delta G(obs) to
      actual hydrogen bond strengths and other aspects of enzyme-ligand and solvent
      ligand interactions.

PMID- 8251527
TI  - Thermal stability of protein secondary structure in Langmuir-Blodgett films.
AB  - The temperature dependence of the secondary structure of photosynthetic reaction
      centres from Rhodobacter sphaeroides in solution and in Langmuir-Blodgett film
      was studied by circular dichroism. It was shown that the secondary structure of
      the protein was not affected in Langmuir-Blodgett films by heating up to 200
      degrees C, while in solution it was completely lost at 55 degrees C. Molecular
      order rather than decreased hydration degree was held responsible.

PMID- 8251528
TI  - 1 alpha, 25-Dihydroxyvitamin D3 and 19-nor-1 alpha, 25-dihydroxyvitamin D2
      suppress immunoglobulin production and thymic lymphocyte proliferation in vivo.
AB  - BALB/CANNHSD female mice were intraperitoneally (i.p.) injected with 1,25
      dihydroxyvitamin D-3 (1,25-(OH)2D3) (20 ng/day) or 19-nor-1,25-(OH)2D2 (100
      ng/day) for 7 days and then given the same dose every other day thereafter until
      day 17 for measuring cell-mediated immunity and on day 33 for observing
      immunoglobulin production. To observe Ig production, the mice were immunized with
      an injection of hemocyanin (150 microgram/0.1 ml, i.p.) on day 8. On the day 7,
      15 and 20 after immunization, the IgG1, and on day 17 and 20, the IgG3 levels in
      1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 groups were significantly lower than in the
      control group. To measure cell-mediated immunity, mice were sensitized with
      dinitrofluorobenzene (DNFB) on the shaved abdominal skin. The number of thymic
      lymphocytes and their stimulation index were significantly reduced by 1,25
      (OH)2D3 and 19-nor-1,25-(OH)2D2. These results demonstrate that 1,25-(OH)2D3 and
      19-nor-1,25-(OH)2D2 can suppress immunoglobulin production and thymic lymphocyte
      proliferation in vivo. 19-Nor-1,25-(OH)2D2 at doses of 100 ng/day was less
      effective than 1,25-(OH)2D3 at doses of 20 ng/day.

PMID- 8251529
TI  - The induction of lipid peroxidation by E. coli lipopolysaccharide on rat
      hepatocytes as an important factor in the etiology of endotoxic liver damage.
AB  - Oxygen-derived radicals have been suggested to produce tissue injury during
      endotoxic shock by initiating lipid peroxidation. In order to investigate the
      induction of lipid peroxidation by Escherichia coli 0111:B4 lipopolysaccharide
      (LPS) on hepatocytes, malondialdehyde (MDA) and superoxide dismutase (SOD)
      activity have been evaluated in vivo and in vitro using two experimental models:
      rat liver after the establishment of endotoxic reversible shock, and cultured
      hepatocytes after treatment with LPS. Liver MDA levels were increased in vivo
      during the acute-phase of endotoxic shock, decreasing below control values in the
      recovery phase. An inverse pattern was obtained when SOD activity was measured,
      consistent with an active system of cellular protection. Similar results were
      obtained in vitro after treatment of cultured hepatocytes with LPS (50
      micrograms/ml), thus indicating that a direct LPS cytotoxic effect on hepatocytes
      exits during the endotoxic process. The direct LPS interaction induced
      alterations in Ca2+ permeability of hepatocyte plasma membrane as detected by
      flow cytometry using the fluorescent probe Indo-1.

PMID- 8251530
TI  - Antiplatelet protease, kistomin, selectively cleaves human platelet glycoprotein
      Ib.
AB  - Kistomin, a metalloprotease purified from venom of Calloselasma rhodostoma, dose-
      and time-dependently prolonged the latent period of aggregation and inhibited ATP
      secretion of human washed platelets stimulated by thrombin. It inhibited
      aggregation induced by low concentrations of thrombin (< or = 0.2 U/ml) whereas
      it had only slight effect on aggregation induced by high concentrations of
      thrombin (> or = 0.5 U/ml). Meanwhile it also inhibited ristocetin-induced
      platelet aggregation in a dose- and time-dependent manner. It significantly
      inhibited cytosolic calcium rise of Quin 2--loaded platelets, completely blocked
      thromboxane B2 formation, and blocked [3H]inositol phosphates formation of
      [3H]myoinositol loaded platelets stimulated by 0.1 U/ml of thrombin. Kistomin
      inhibited significantly thromboxane but not [3H]inositol phosphates formation of
      platelets stimulated by a high concentration of thrombin (1 U/ml). Incubation of
      platelets with kistomin resulted in a selective cleavage of platelet membrane
      glycoprotein Ib as revealed by SDS/PAGE stained by periodic acid/Schiff reagent.
      These results suggested that thrombin activates platelets at least through two
      receptors/or effectors-mediated events. In addition to glycoprotein Ib, other
      surface membrane component(s) (e.g., the seven transmembrane domain thrombin
      receptor) may also be important in regulating the biochemical events of human
      platelets in response to thrombin. However, the extent and rate of platelet
      aggregation stimulated by low concentrations of thrombin ( < or = 0.2 U/ml) are
      closely related with the intactness of glycoprotein Ib.

PMID- 8251531
TI  - Photochemical treatment with the lysosomally localized dye tetra(4
      sulfonatophenyl)porphine results in lysosomal release of the dye but not of beta
      N-acetyl-D-glucosaminidase activity.
AB  - Tetra(4-sulfonatophenyl)porphine (TPPS4) sensitizes cells to photoinactivation
      mainly through formation of singlet oxygen. In human cervix carcinoma cells of
      the line NHIK 3025 TPPS4 localizes to a large extent in lysosomes as previously
      shown by fluorescence microscopical and spectroscopical techniques. In the
      present study photodamage to lysosomes was investigated. This was accomplished by
      measuring the activity of the lysosomal marker enzyme beta-N-acetyl-D
      glucosaminidase (beta-AGA) after photochemical treatment (PCT). beta-AGA activity
      was highly sensitive to light exposure in the presence of TPPS4. The enzymatic
      activity was reduced by approximately 70% by non-lethal doses of photochemical
      treatment, indicating that inactivation of lysosomal hydrolases is not likely to
      contribute significantly to the cytotoxic effects of PCT. Centrifugation studies
      showed that TPPS4, but not beta-AGA activity, was released from lysosomes after
      light exposure. 20-30% of the total beta-AGA activity was resistant to the
      photochemical treatment. This was due to beta-AGA activity in Golgi-derived
      vesicles (4-5%) and in vesicles with similar density as lysosomes but not
      containing TPPS4. The present results indicate that lysosomal hydrolases are
      inactivated by photochemical treatment before they eventually escape the
      lysosomal compartment.

PMID- 8251532
TI  - Iron-thiolate induced oxidation of methionine to methionine sulfoxide in small
      model peptides. Intramolecular catalysis by histidine.
AB  - Peptides containing either glycine and methionine, or glycine, methionine and
      histidine at various locations were oxidized by the dithiothreitol/ferric
      chloride system in phosphate buffer. The yields of peptide degradation and
      sulfoxide formation were measured as a function of peptide sequence and pH. In
      general little change of the final yields of peptide degradation is observed
      whereas the final yields of sulfoxide formation progressively decrease on going
      from pH 6.0 to 8.0. The pH profiles vary with the structure of the respective
      peptide. Efficient sulfoxide formation occurred when histidine and methionine
      were present within the same peptides sequence, and particularly when methionine
      was located at the C-terminus of the peptide. Added superoxide dismutase,
      catalase, and methanol did neither promote nor inhibit both the degradation of
      peptide and the formation of sulfoxide excluding free superoxide, hydrogen
      peroxide, and hydroxyl radicals as responsible reactive oxygen species. The
      observations are rationalized by invoking a pH-dependent conversion of an
      efficiently sulfoxide yielding oxidant into another oxidant which still degrades
      peptides but does not form methionine sulfoxide. The first might be a metal-bound
      peroxide or peroxyl species which converts into a metal-bound or 'complexed'
      hydroxyl radical.

PMID- 8251533
TI  - Stabilization of microtubules by dynein-binding in vitro. Stability of
      microtubule-dynein complex.
AB  - We have studied the effects of dynein binding on the stability of microtubules in
      vitro, using Tetrahymena ciliary dynein and microtubules (three-cycled purified
      microtubules: 3 X-Mts and phosphocellulose-column purified microtubules: PC-Mts).
      To determine the relative stability of the microtubules, we first prepared the
      microtubules bound with dynein (Mts--dynein complex) and subjected the Mts-dynein
      complex to treatments that depolymerize the microtubules, such as dilution to
      below critical concentration of tubulin, calcium ions and lower temperature. Dark
      field microscopy revealed that the microtubules in the Mts--dynein complex
      appeared intact under conditions which otherwise result in microtubule
      depolymerization. However, when dynein was dissociated from the Mts--dynein
      complex with addition of ATP, no microtubule was found in the specimens under the
      same conditions. That is, the microtubules in the Mts--dynein complex did not
      depolymerize upon dilution with the buffer solution to below critical
      concentration of tubulin. However, addition of ATP to the diluted specimen caused
      dynein to become separated from the Mts, resulting in complete depolymerization
      of the microtubules. Stability of the microtubules was also studied by the
      turbidity changes and was confirmed by the patterns of stained gel bands in
      electrophoresis. With the addition of calcium ion, the Mts--dynein complex
      decomposed into separate molecules dynein and tubulin. At the lower temperature
      of 0 degrees C, the 3 X-Mts--dynein complex was decomposed into dynein and
      tubulin, while the microtubules in the PC-Mts--dynein complex did not
      depolymerize. Although we have not yet studied the effects of cytoplasmic dynein
      binding on the microtubules, the results suggest that the stabilizing effect of
      dynein binding to the microtubules is one of the important functions of dynein in
      vivo.

PMID- 8251534
TI  - Solubilization and characterization of the acceptor for Clostridium botulinum
      type B neurotoxin from rat brain synaptic membranes.
AB  - The acceptor for Clostridium botulinum type B neurotoxin was solubilized from rat
      brain synaptic membrane with nonionic detergent, nonanoyl-N-methylglucamide (MEGA
      9). The solubilized acceptor was assayed for the binding activity by
      precipitating the acceptor with acetone in the presence of phosphatidylcholine.
      125Ilabeled neurotoxin specifically bound to the lipid vesicles having
      incorporated the acceptor together with gangliosides. The lipid vesicles having
      incorporated either the acceptor or gangliosides alone showed extremely low
      binding activity. The treatment of the solubilized acceptor with lysyl
      endopeptidase and glycopeptidase F but not with sialidase resulted in decreased
      toxin binding, indicating that the putative acceptor is a glycoprotein
      accompanying an N-linked carbohydrate moiety. The observations suggest also that
      a protein acceptor/ganglioside complex may be required to form the functional
      toxin receptor.

PMID- 8251535
TI  - Identification of protein disulfide isomerase and calreticulin as autoimmune
      antigens in LEC strain of rats.
AB  - Long Evans Cinnamon (LEC) rats, showing spontaneous hereditary hepatitis and
      hepatic carcinoma, were found to possess autoimmune antibodies to liver
      microsomal proteins, particularly to proteins with the molecular weight of 56kD
      and 55kD. The antibodies occurred in association with acute lethal hepatitis in
      the LEC rats in our previous study. Two-dimensional immunoblot analysis of the
      antigenic proteins revealed that the 56kDa and 55kDa proteins showed 4.2 and 4.0
      pI values and were estimated to be protein disulfide isomerase (PDI) and
      calreticulin, respectively, from NH2-terminal amino acid sequence analysis. These
      proteins were further identified by immunoblot analyses using purified proteins
      and specific antibodies. PDI was a major autoimmune antigenic protein.

PMID- 8251536
TI  - Purification and reconstitution of the methyl-accepting chemotaxis proteins from
      Bacillus subtilis.
AB  - The methyl-accepting chemotaxis proteins (MCPs) from Bacillus subtilis,
      designated as H1, H2, and H3, have been purified to near homogeneity. These
      purified MCPs were reconstituted into proteoliposome vesicles using a detergent
      dilution procedure. The ability of the reconstituted MCPs to be methylated in
      vitro strongly suggests that they are in a functionally active conformation. The
      MCPs of B. subtilis are considerably larger than those of Escherichia coli, with
      molecular weights of the purified proteins being 76, 86, and 97 kDa for H3, H2,
      and H1, respectively. Two-dimensional electrophoresis demonstrates that the
      isoelectric point of H1 and H2 is 5.1, while H3 is slightly more basic, having an
      isoelectric point of 5.3. Immunoblot analysis using the cross reacting E. coli
      anti-Trg antibody reveals that maximal MCP expression occurs approx. 4 h after
      the onset of stationary phase, and remains relatively stable thereafter. However,
      the ability of the MCPs to be methylated in vivo is significantly reduced.

PMID- 8251537
TI  - A tale of two diagnoses: revisited.

PMID- 8251538
TI  - The dually diagnosed patient with psychotic symptoms.
AB  - The dual diagnoses of substance use disorder with other psychiatric disorder is
      especially problematic in psychotic or other chronically mentally ill patients.
      Such patients have a more fragile mental status which can be adversely affected
      by psychoactive substances of abuse. In addition, most such patients need to take
      potent psychiatric medications which themselves may interact with substances.
      This article reviews substance induced versus true comorbid major psychiatric
      disorders and discusses the major classes of psychiatric medications in terms of
      abuse potential and their abilities to either help or hinder substance disorder
      recovery.

PMID- 8251539
TI  - Outpatient vs. inpatient treatment for the chronically mentally ill with
      substance use disorders.
AB  - Treatment decisions about complex patients with both substance use disorders and
      chronic mental illness cannot be reduced to an inpatient vs. outpatient
      dichotomy. Treatment progresses through a series of stages, in each of which we
      must make decisions about treatment settings and approaches. I discuss treatment
      decisions within the framework of a staged treatment model, reviewing decisions
      to be made during stabilization, engagement, persuasion, active (or primary)
      treatment, and relapse prevention (or aftercare).

PMID- 8251540
TI  - An integrated psychology for the addictions: beyond the Self-Medication
      Hypothesis.
AB  - The Self-Medication Hypothesis (SMH) is a popular explanation for chemical
      dependencies. The SMH ignores or leaves out important biological research which
      has explored the mechanisms of reward, motivation to use alcohol/drugs, as well
      as the impact on mood of chronic, excessive alcohol/drug use. A new psychology is
      needed which includes this biological research as well as the psychological
      observations contained in the SMH. Self Psychology is used to create an
      integrated psychology for the addictions.

PMID- 8251541
TI  - Pharmacotherapy of psychiatric syndromes with comorbid chemical dependence.
AB  - Because of the paucity of research on the pharmacotherapy of psychiatric
      syndromes with comorbid psychoactive substance use disorders, treatment
      guidelines are primarily drawn from general principles of clinical
      psychopharmacology and the addictive disease model. Effective treatment requires
      the determination of a discrete psychiatric diagnosis or working differential,
      consideration of the range of drug effects as they vary over time, and awareness
      of potential pharmacologic interactions between medication and alcohol or drug
      use. Either nonspecific prescribing or failure to treat may result in protracted
      dysfunction, relapse, or medical morbidity and mortality. Pharmacotherapy may
      also determine whether treatment results in mere abstinence vs. recovery from
      addictive disease. Primary emphasis on non-pharmacologic strategies and the use
      of a formal treatment contract increase the likelihood of successful
      pharmacotherapy outcome.

PMID- 8251542
TI  - Genetic and family studies in psychiatric illness and alcohol and drug
      dependence.
AB  - The high prevalence of comorbid psychiatric disorders among patients with
      substance dependence both confuses diagnosis and complicates treatment. One way
      of separating substance dependence and comorbid conditions is to use the family,
      rather than the individual, as the unit of study. Results from family, twin, and
      adoption studies indicate the existence of a heritable and specific liability to
      alcohol dependence independent of other psychiatric disease, and perhaps to other
      substance dependence, as well. However, substance dependence, like many other
      psychiatric disorders, is a clinically and etiologically heterogeneous entity,
      which both complicates patterns of familial transmission and underlines the need
      for more precise description of subforms of illness.

PMID- 8251543
TI  - Comorbidity of addictive and psychiatric disorders.

PMID- 8251544
TI  - The epidemiology of the comorbidity of psychiatric and addictive disorders: a
      critical review.
AB  - Assessing the prevalence of the comorbidity of psychiatric and addictive disease
      using epidemiologic methods results in artifactually high rates. Use of a
      clinical sample will yield falsely high rates, because substance use is
      associated with exacerbation of mental illness. Cross sectional design will
      inflate rates of psychiatric comorbidity in addicts, who attribute substance use
      to psychological symptoms until well into recovery. Application of exclusionary
      criteria for independent diagnosis is subject to investigator bias, particularly
      about the unproven yet popular "self-medication" hypothesis. The psychiatric
      symptoms which are common in active addiction generally clear within weeks to
      months of treatment for addiction but do not respond to standard
      psychopharmacologic treatment for primary mental illness. When lengthy follow up
      periods are employed, substance induced psychiatric syndromes typically resolve.
      We conclude that while patients treated in psychiatric settings often have
      comorbid and independent addictive illness, patients treated in addiction
      settings uncommonly have comorbid psychiatric illness despite common psychiatric
      symptoms.

PMID- 8251545
TI  - Comorbidity of psychiatric and alcohol/drug disorders: interactions and
      independent status.
AB  - Dual diagnosis as interpreted in clinical psychiatric practice is often not what
      the term means-two independent disorders. Commonly, addiction disorders are
      attributed to self medicating of "underlying" psychiatric disorders, there by, a
      contingency status. However, studies and clinical addiction practice show that
      drug and alcohol addiction must be afforded an independent status before accurate
      assessment and assignment of interactions in dual diagnosis can be made in
      clinical conditions. Studies also show rates for psychiatric comorbidity are low
      in addiction populations and rates for addictive disorders are high in
      psychiatric populations. If the common denominator is taken as addiction, then
      the perspective of the setting and examiner become crucial in determining
      prevalence rates for both disorders. Most importantly, effective treatment of
      either disorder will not occur unless an agreement on an independent status is
      accepted for both addictive and psychiatric disorders in any patient population
      setting.

PMID- 8251546
TI  - Evaluation and acute management of psychotic symptomatology in alcohol and drug
      addictions.
AB  - The practical clinical evaluation of patients manifesting psychotic
      symptomatology and addictive illness is approached in diverse and contradictory
      ways. While addiction specialists may not recognize the existence of Axis I
      disorders that prevent the utilization of treatment in the system, trained mental
      health professionals are traditionally prone to deny or minimize the addictive
      process and its capacity to produce psychiatric symptoms. This may result in
      premature diagnosis, and in a poor response to psychiatric treatment. The purpose
      of this paper is to describe a pragmatic model, based on clinically observable
      conditions, for the evaluation and acute management of major psychiatric
      symptomatology associated with diagnosed drug and alcohol addiction. Before
      describing the model, psychotic illness and symptoms in the general population
      versus the drug and alcohol addicted will be examined. The model will be applied
      to a few discrete syndromes based on common clinical presentations.

PMID- 8251547
TI  - Affective and anxiety disorders and alcohol and drug dependence: diagnosis and
      treatment.
AB  - Depression and anxiety frequently coexist in patients with substance use
      disorders. This clinically-oriented article examines the relationship between
      these conditions and emphasizes data showing that substances of abuse can cause
      signs and symptoms of both depression and anxiety. These substance-related
      syndromes appear to have a different course and prognosis than uncomplicated,
      independent anxiety and major depressive disorders, and clinicians should
      consider the role of alcohol and other drugs in all patients presenting with
      these complaints. The authors also outline an approach for diagnosing and
      managing patients with the combination of a substance use and depressive or
      anxiety disorder.

PMID- 8251548
TI  - Pathological gambling, eating disorders, and the psychoactive substance use
      disorders.
AB  - Both pathological gambling and the eating disorders have been conceptualized as
      addictive diseases, comparable to alcoholism and other drug dependencies. This
      paper briefly reviews both pathological gambling and the eating disorders,
      stressing their epidemiology and their overlap with psychoactive substance use
      and other psychiatric disorders. Common factors in the natural history and
      treatment of these disorders are also discussed.

PMID- 8251549
TI  - On-line post-column Diels-Alder derivatization for the determination of vitamin
      D3 and its metabolites by liquid chromatography/thermospray mass spectrometry.
AB  - Liquid chromatography/thermospray mass spectrometry (LC/TSP MS) has been used for
      the determination of vitamin D3 and some of its metabolites, i.e. 1 alpha(OH)
      vitamin D3, 25(OH) vitamin D3, 1 alpha,25(OH)2 vitamin D3 and 24,25(OH)2 vitamin
      D3, using positive and negative ion detection. Using these two modes positional
      isomers can be identified. Detection in the negative ion mode was preferred
      because of the slightly higher sensitivity. The limits of detection, using
      multiple ion detection, are 50-100 nM (6-12 pmol injected). On-line post-column
      derivatization based on [4 + 2] cyclo-addition (Diels-Alder reaction) proceeds
      within 1 min at room temperature. If this step is included in LC/TSP MS, the
      detection limits of the analytes can be improved 7-70-fold depending on the
      analyte tested. The best results (detection limits down to 1 nM, i.e. 0.12 pmol
      injected) are obtained with discharge ionization in the negative ion mode.

PMID- 8251551
TI  - Determination of serum creatinine by isotope dilution method using discharge
      assisted thermospray liquid chromatography/mass spectrometry.
AB  - A discharge-assisted thermospray (plasmaspray) liquid chromatography/mass
      spectrometric method for the determination of serum creatinine is described. The
      method incorporates stable isotope dilution using (D3)creatinine as an internal
      standard. Separation is performed in reversed-phase high-performance liquid
      chromatography using 0.01 M aqueous ammonium acetate as a flow solvent. Effluents
      are directly introduced to the mass spectrometer and [MH]+ ions are monitored
      during LC/MS using the selected ion monitoring method. Satisfactory agreement
      between the analytical result and the certified value of the serum sample of
      standard reference material and relative standard deviation ranging from 0.6% to
      1.2% was obtained.

PMID- 8251550
TI  - Simultaneous analysis of diphenhydramine and a stable isotope analog
      (2H10)diphenhydramine using capillary gas chromatography with mass selective
      detection in biological fluids from chronically instrumented pregnant ewes.
AB  - This report describes both the synthesis of a stable isotope analog of the H1
      receptor antagonist diphenhydramine (DPHM), and the simultaneous quantitation of
      DPHM and a deuterated stable isotope analog of DPHM, viz. (2H10)DPHM in
      biological fluids from the chronically instrumented pregnant ewe. (2H10)DPHM was
      synthesized and purified, and both its structure and purity were verified.
      Biological samples were prepared for analysis using liquid-liquid extraction
      prior to capillary gas chromatography/mass spectrometry. The method employed
      electron impact ionization with selective ion monitoring of ions with m/z 165 for
      DPHM and m/z 173 for (2H10)DPHM. The minimal quantifiable concentration of DPHM
      and (2H10)DPHM from a 1.0 ml sample was 2.0 ng ml-1 in fetal and maternal plasma,
      fetal tracheal fluid and amniotic fluid. The method was validated from 2.0 ng ml
      1 to 200.0 ng ml-1 for both DPHM and (2H10)DPHM in plasma, fetal tracheal fluid
      and amniotic fluid. Differences in the disposition between DPHM and (2H10)DPHM
      were not apparent during a control experiment in which both labeled and unlabeled
      DPHM were administered to a chronically instrumented fetal lamb. This method
      provides the required sensitivity and selectivity for the simultaneous
      quantitation of unlabeled and labeled DPHM during pharmacokinetic experiments
      conducted in near-term pregnant sheep.

PMID- 8251552
TI  - The characterization of two biliary glutathione conjugates of amsacrine using
      liquid secondary ion mass spectrometry.
AB  - An additional biliary glutathione (GSH) conjugate of the anilinoacridine anti
      tumour agent amsacrine (4'-(9-acridinylamino)methanesulphon-m-anisidide, NSC
      249992) has been identified in bile collected from male Wistar rats by
      cannulation of the common bile duct and from male BDF1 mice by removal of the
      gall bladder after treatment with amsacrine. The presence of this conjugate, at
      the 6'-position of the anilino ring, has been confirmed by liquid secondary ion
      (LSI) mass spectrometric analysis of selected biliary metabolites separated by
      high-performance liquid chromatography. The two major metabolites each gave a
      daughter ion spectrum which was diagnostic for either 5'- or 6'-GSH conjugation.
      This pattern was confirmed by comparison with LSI mass spectral data obtained
      from authentic chemical standards formed on reaction of the quinone diimine
      derivative of amsacrine with methanethiol or mercaptoethanol.

PMID- 8251553
TI  - Medallion, with MSV support, goes statewide.

PMID- 8251554
TI  - Prior authorization made simple.

PMID- 8251555
TI  - Primary care in Virginia--in decline.

PMID- 8251556
TI  - Rural Virginia. As country doctors retire, who waits in the wings? Conference
      studies problems of rural health care.

PMID- 8251557
TI  - Kidney disease in the child.

PMID- 8251558
TI  - Angioedema secondary to ACE inhibitors.

PMID- 8251559
TI  - Double whammy.

PMID- 8251560
TI  - The future of teaching hospitals in Virginia.

PMID- 8251561
TI  - Leveling the playing field in a competitive market: the UVa Health Sciences
      Center and state regulation.

PMID- 8251562
TI  - The health care crisis--how we got there.
AB  - There are upward pressures on the medical economy that we can do little to
      control. Among these are general inflationary factors, high technology costs, and
      care for a population ever increasing in age. Nothing in the way of reform is
      likely to come out of Washington other than another bureaucratic scheme which
      will add further confusion and put in place another multilayered system. Many of
      the wrongs I have cited can and should be corrected. By changing those wrongs
      into rights we can preserve the best of our present system, including two
      American icons: fee-for-service and freedom-of-choice of physician. Let us not
      swap the devil for the witch.

PMID- 8251563
TI  - Macrophage-pathogen interactions. Introduction.

PMID- 8251564
TI  - Antigen processing and presentation.

PMID- 8251565
TI  - Macrophages as producers of chemotactic proinflammatory cytokines.

PMID- 8251566
TI  - Production of active oxygen species by phagocytic leukocytes.

PMID- 8251567
TI  - Antiparasitic effects of nitric oxide in an in vitro murine model of Chlamydia
      trachomatis infection and an in vivo murine model of Leishmania major infection.

PMID- 8251568
TI  - Antimicrobial mechanisms: antimicrobial polypeptides of mononuclear phagocytes.

PMID- 8251569
TI  - Suppressor macrophages.

PMID- 8251570
TI  - Macrophage-natural killer cell interactions in resistance to mycobacteria.

PMID- 8251571
TI  - Macrophage resistance genes: Bcg/Ity/Lsh.

PMID- 8251572
TI  - Macrophages and Mycobacterium tuberculosis: the key to pathogenesis.

PMID- 8251573
TI  - Monocyte-Mycobacterium avium complex interactions: studies of potential virulence
      factors for humans.

PMID- 8251574
TI  - The role of the macrophage in resistance to the leprosy bacillus.

PMID- 8251575
TI  - Macrophage activation: a riddle of immunological resistance.
AB  - Various lines of defense against infection are present in all living creatures.
      The balance between symbiosis and parasitism is determined by the mechanisms
      through which the host resists infection and by the extent of injury induced by
      the parasite: both factors contribute to disease. Lines of host defense can be
      arbitrarily divided into three components: 1) barrier functions of skin and
      mucous membranes and their innate physical and secretory antimicrobial
      components; 2) elements of host defense that do not necessarily require prior
      exposure to an infectious agent or immunologic memory (mast cells, granulocytes,
      macrophages, NK cells, gamma/delta T cells); and 3) immune responses directed
      against specific epitopes on the infectious agent induced by prior exposure and
      immunologic memory (alpha/beta T cells, B cells). Analysis of such host defense
      mechanisms repeatedly documents tremendous redundancy and overlap between these
      lines of defense. Further, there is open communication, so that a change at any
      one level ripples throughout the system. Acquired nonspecific resistance to
      infection is an example of such a ripple. Host response to one infection alerts
      the immune system, so that the general level of resistance to other infectious
      agents is increased. This response is initiated by an immune response (third line
      of defense) but effected by nonspecific elements (second line of defense). The
      survival value of such responses is obvious. There are numerous examples in both
      mouse and man of the operation of these systems in response to infection.
      Further, the menus of antimicrobial components available to both mouse and man
      for resistance to infection are very similar, but not identical. Indeed, it is
      said that the genetic basis for differences between mice and man revolve around a
      difference of less than 10% in DNA sequences. But there are differences! Mouse
      macrophages produce IFN-beta in response to infection, human cells produce IFN
      alpha. Mouse macrophages effect antimicrobial activity principally through
      induction of NO synthase and the generation of toxic nitrogen oxides. This
      pathway has yet to be described with human macrophages. In both man and mouse, F.
      tularensis is an obligate intracellular parasite of macrophages that requires an
      essential component provided by the cell for its replication. That mouse and man
      are not so different is well illustrated by the effector mechanisms induced by
      IFN-gamma for antimicrobial activity against F. tularensis.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8251576
TI  - Introduction: the proliferation and differentiation of macrophages.

PMID- 8251577
TI  - The intracellular nature of Salmonella infection during the early stages of mouse
      typhoid.
AB  - In mouse enteric fever (typhoid) infection with S. typhimurium, the bacteria
      appear to grow intracellularly, and at least during the early phase of infection
      they are in splenic PMNs rather than macrophages. Inflammation caused by
      salmonella infection and other infections, such as MHV, results in inflammatory
      responses that enhance resistance to salmonella infection. At least in the case
      of MHV, this effect is most pronounced on the rate of salmonella growth. Since
      the effects of the Ity locus on salmonella growth rate are readily seen during
      the first few days of infection, when salmonella are primarily within PMNs, the
      Ity locus is able to mediate its effect on salmonella pathogenesis in PMNs in
      vivo. Whether or not macrophages play a predominant role in salmonella
      pathogenesis later in infection is not yet known.

PMID- 8251578
TI  - Macrophage-Listeria interactions.
AB  - It is clear that the interaction between macrophages and the facultative
      intracellular bacterium Listeria monocytogenes is complex and dictated by the
      needs of both organisms. On the one hand, the invading pathogen has devised
      strategies to locate itself intracellularly in a site where host defense
      mechanisms are minimal; thus it escapes the phagosome and enters the cytoplasm,
      from which it travels to the next cell without exposing itself to the
      extracellular environment. On the other hand, the infected cell, potentially a
      highly efficient killer of microbes, is influenced by cytokines and other
      mediators, autocrine and exocrine, that enhance its ability to thwart the
      invader. Thus a macrophage, under the influence of at least IFN-gamma and TNF
      alpha, can progress from being a nonlistericidal cell to one that can kill the
      intracellular organism. It probably does this by preventing escape of Listeria
      from the phagosome into the cytoplasm. The bacterium, retained in the phagosome,
      is killed by unknown mechanisms, which appear to be regulated by iron and may
      involve reactive nitrogen intermediates.

PMID- 8251579
TI  - Legionella and macrophages.

PMID- 8251580
TI  - Life and death of an intracellular pathogen: Francisella tularensis and the
      macrophage.

PMID- 8251581
TI  - Macrophages and Brucella.
AB  - The studies reviewed here indicate that during the course of infection with B.
      abortus protective immune responses occur and that macrophages are activated for
      antimicrobial activity in both susceptible and resistant animals. Yet in
      susceptible animals chronic infections with B. abortus become established. There
      is circumstantial evidence from experiments in vitro that the outcome of
      infection is related to macrophage/Brucella interactions. This includes the
      following: 1) the virulence of strains of B. abortus is proportional to their
      ability to inhibit host phagocyte functions and to survive in murine, bovine, and
      guinea pig macrophages; and 2) the ability of guinea pig and bovine macrophages
      to inhibit intracellular growth of brucellae is directly proportional to the
      innate resistance of the host from which the macrophages were derived. In the
      murine model, the relative resistance of C57Bl/10 mice to infection with virulent
      B. abortus strain 2308 correlated with more efficient clearance during the first
      week following infection, compared with the susceptible BALB/c strain. It is not
      known whether this was due to innate differences in the recruitment or
      bactericidal activities of macrophage populations in the two mouse strains, as
      demonstrated with L. monocytogenes, or to other nonimmune factors such as natural
      killer cells secreting IFN-gamma and lysing infected macrophages following direct
      interaction with the brucellae, as shown with other intracellular bacteria. It is
      also of interest that clearance of strain 2308 following the plateau phase was
      slower in BALB/c than in C57Bl/10 mice. Since at this time protective T cells are
      known to be present in the spleens of BALB/c mice, this difference may have been
      due either to more efficient clearance of brucellae by C57Bl/10 macrophages
      following activation with T cell cytokines, or to the inability of immune T cells
      to interact with Brucella-infected macrophages in the susceptible BALB/c strain.
      CD8 T cells have been shown to have an important role in clearance of brucellae
      following the peak of infection and may act by lysing chronically infected
      macrophages. Although protective T cells have been demonstrated in susceptible
      strains of mice, chronically infected macrophages in these animals may fail to
      act as targets or may down-regulate T cell functions. As a result, infected
      macrophages could persist in the presence of Brucella-specific T cells.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8251582
TI  - Interactions between macrophages and chlamydiae.

PMID- 8251583
TI  - Rickettsiae and macrophages.

PMID- 8251584
TI  - Alveolar macrophage interaction with Pneumocystis carinii.

PMID- 8251585
TI  - Interactions between Leishmania major and macrophages.

PMID- 8251586
TI  - Immune effector role of macrophages in experimental schistosomiasis mansoni.

PMID- 8251587
TI  - The molecular biology of macrophage activation.

PMID- 8251588
TI  - Toxoplasma-macrophage interactions.

PMID- 8251589
TI  - Macrophages in experimental Chagas' disease.
AB  - The foregoing provides a basis for considering that macrophages are important in
      basically every aspect of the host-parasite relationship in experimental Chagas'
      disease. The myriad of activities of macrophages and the diverse responses of
      these cells to T. cruzi and various stimulatory and inhibitory cytokines as
      measured both in vitro and in vivo are suggestive of the complexity of the cell
      cell interactions of the host during the course of infection and the evasive
      activities of the parasite.

PMID- 8251590
TI  - Macrophage interactions with Candida.
AB  - The monocyte/macrophage, in comparison to the neutrophil, would appear to have a
      limited role in protection against C. albicans. This statement is based on the
      observations of several investigators who report that these cells have very
      little killing capacity unless they are activated by cytokines such as IFN-gamma
      and GM-CSF. The mechanisms of killing by these cells appear to include both
      oxidative and nonoxidative mechanisms, the latter perhaps being more important.
      The mechanisms of killing may be different for monocytes and macrophages.
      Granulocyte-macrophage colony-stimulating factor and its effect on monocytes has
      been studied using Candida as a target organism. Two explanations for the
      enhancement of monocyte killing by this cytokine have been proposed: GM-CSF
      augments both superoxide anion and the level of mannose receptors on treated
      monocytes. Both of these changes could be significant in the increased killing
      capacity of these cells.

PMID- 8251591
TI  - Interaction of Histoplasma capsulatum yeasts and conidia with human and animal
      macrophages.

PMID- 8251592
TI  - Macrophage-Cryptococcus interactions.
AB  - Macrophages are a heterogeneous population that vary depending on their species
      of origin, anatomic location, state of activation, and conditions of culture.
      Moreover, macrophages normally interact with other cells both within and without
      the immune system. It is clear from the data reviewed in this chapter that all of
      these aforementioned variables greatly influence macrophage-C. neoformans
      interactions. While circumstantial evidence strongly supports a major role for
      the macrophage in host defenses against cryptococcosis, the nature and extent of
      the contribution macrophages make remain to be defined. One major challenge for
      researchers in this field will be to design experiments that closely mimic what
      occurs in human physiological and pathological states.

PMID- 8251593
TI  - Macrophage-Aspergillus interactions.

PMID- 8251594
TI  - Macrophages and Blastomyces dermatitidis.

PMID- 8251595
TI  - The macrophage and HIV-1.
AB  - As described above, monocytes/macrophages from such diverse areas as the CNS,
      lungs, peripheral blood, cord blood, and liver are susceptible to infection by
      HIV-1 and may serve as reservoirs for transmitting the virus throughout the body.
      In contrast to lymphocytes, the chronic and low-level mode of infection that HIV
      1 takes on within monocytes/macrophages allows these cells to contribute to
      persistent viral infection. Infection of these cells by HIV-1 can alter a variety
      of their immunological functions such as cytokine production, chemotaxis,
      accessory cell function, and microbicidal activity. Furthermore, macrophages and
      macrophage-related microglial cells in the brain and CSF are thought to play a
      critical role in the pathogenesis of CNS disease. Infection with HIV-1 in
      monocytes/macrophages is regulated in an autocrine manner by a panel of cytokines
      and other soluble factors. Most HIV-1 isolates exhibit specific tropism for
      monocytes/macrophages, lymphocytes, or, in some cases, both cell types; this
      phenomenon of tropism may be linked to structural variabilities between different
      isolates. While in vitro studies clearly demonstrate that the replicating cycle
      of HIV-1 in monocytes/macrophages differs from its replicating cycle in
      lymphocytes, elucidation of the role of monocyte/macrophages in mediating the
      severe immunosuppression characteristic of AIDS is far more from complete, and
      further investigation into the role of monocytes/macrophages in the
      immunopathogenesis of HIV-1 infection is necessary to design therapeutic
      approaches to control viral infection and disease progression.

PMID- 8251596
TI  - Lentivirus infection of macrophages.
AB  - The ovine and caprine lentiviruses infect monocytes, and the viral DNA is
      integrated into the cellular DNA. The provirus remains silent until the monocyte
      matures into a macrophage. Intrinsic to this maturation is the induction of a
      class of immediate early genes in the monocyte that includes the transcription
      factors JUN and FOS. These transcription factors are thought to couple short-term
      signals in the cell to long-term cellular differentiation by regulation of
      specific cellular genes. Thus, JUN and FOS bind to the AP-1 site in the promoters
      of cellular genes and activate their transcription, resulting in maturation of
      the monocyte into a macrophage. In addition, these cellular factors activate the
      same AP-1 sequence in the visna virus LTR, leading to transcriptional activation,
      full viral gene expression, and production of progeny virus. The expression of
      viral antigens in the context of MHC class II on the macrophage leads to the
      production of cytokines and a lymphoproliferative response that causes the
      lesions in specific target organs in an infected animal. We still understand only
      the framework of these events. The specific mechanisms by which viral genes alter
      macrophage gene expression and the molecular basis of different viral tropism for
      specific tissue macrophages, i.e. microglia, remain to be determined.

PMID- 8251597
TI  - Transmembrane and intracellular signaling events in lipopolysaccharide-stimulated
      macrophages.

PMID- 8251598
TI  - [The anesthesia recovery room--new demands on an established form of
      organization].

PMID- 8251599
TI  - [The present status of blood filtration--fundamentals and the clinical
      significance of leukocyte depletion and microaggregate filters in blood
      transfusion].
AB  - In this review the role of the latest generation of leukodepletion blood filters
      and the adverse reaction of leukocytes i.e. alloimmunisation, immunosuppression,
      nonhaemolytic febrile transfusion reaction, platelet refractoriness, transmission
      of infectious agents are described and discussed. Leukocyte-poor blood component
      is indicated for patients with a history of nonhaemolytic febrile transfusion
      reaction, in avoiding alloimmunisation in patients waiting for transplantation or
      platelet refractoriness and in preventing CMV-infection. In the review the role
      of microaggregate filters in transfusion complications, namely, nonhaemolytic
      febrile transfusion reaction, thrombocytopenia, adult respiratory distress
      syndrome (ARDS), fibronectin depletion and histamine release is evaluated. The
      need of microfiltration of autologous blood is discussed. It appears that the use
      of 40 microns microfilters is warranted in a broad array of intensive care
      settings.

PMID- 8251600
TI  - [Patient-controlled administration of alfentanil during interventional measures-
      an alternative to general anesthesia].
AB  - OBJECTIVE: In 360 patients undergoing extracorporal shock wave lithotripsy (ESWL)
      the effects of an opioid analgesia with alfentanil (Rapifen) were investigated.
      METHODS: Starting with an intravenous bolus injection of 30 micrograms/kg
      repetitive injections of 15 micrograms/kg were administered when pain recurred.
      In 12 patients arterial blood samples were taken to determine alfentanil serum
      concentrations and blood gases. The pharmacokinetics of alfentanil were described
      by an open two-compartment model. RESULTS: In spite of multiple applications of
      the opioid no relevant cumulation could be seen. Although the patients received 3
      l/min of oxygen via nasal tube, a significant decrease in paO2 was observed. pH
      was decreased and there was a significantly increased paCO2. No significant
      changes in arterial blood pressure were observed. Two patients developed rigidity
      of the chest wall. CONCLUSION: For short operations with only mild noxious
      stimuli opioid analgesia with alfentanil is a suitable procedure if applied by an
      experienced anaesthesiologist.

PMID- 8251601
TI  - [First aid and prognosis following drowning accidents. Results of a retrospective
      study of 115 cases].
AB  - OBJECTIVE AND STUDY DESIGN: In 115 cases of submersion the initial findings of
      the rescue team, the patients status in the emergency room and the course of
      clinical treatment were analyzed retrospectively. RESULTS: Submersion accidents
      happened preferably in February, March and in the summertime from May to August.
      Most of the accidents took place in public waters or public baths (85.2%).
      Children below 10 years of age were involved in 34.8% of the submersion
      accidents. 57 patients were near drowned and 58 patients were drowned. The
      prognosis of patients with detectable heartbeat at the site of the accident
      depends on the primary pulmonary lesion. If respiratory insufficiency is
      recognized early and treated aggressively by intubation and mechanical
      ventilation with PEEP, these patients have an excellent prognosis. Only one
      patient with detectable heartbeat died, typically, after delayed treatment of
      respiratory failure. 55 patients recovered completely; one patient was suffering
      from a lesion of the n. medianus. Contrariwise, the prognosis of patients without
      detectable heartbeat is mainly determined by the consequences of hypoxaemia and
      is, overall, poor. Though resuscitation succeeds in 50% of submersion victims,
      only one out of four successfully resuscitated patients survived with little or
      no neurologic damage. Severe hypothermia may improve the prognosis of submersion
      victims. CONCLUSION: Thus, there are no useful parameters that would accurately
      predict the individual course of a submersion victim.

PMID- 8251602
TI  - [Anesthesia standards: fact or fiction? Part I].

PMID- 8251603
TI  - [A preoperative fast of not less than 6 hours increases the risk of aspiration-
      fact or fiction?].

PMID- 8251604
TI  - [Hypokalemia (< 3.5 mmol/l) must be treated preoperatively--fact or fiction?].

PMID- 8251605
TI  - [Succinylcholine is contraindicated in kidney insufficiency--fact or fiction?].

PMID- 8251606
TI  - [Before catheterizing the radial artery should an Allen test be carried out?].

PMID- 8251607
TI  - [Perioperative respiratory therapy lowers the risk of respiratory complications-
      fact or fiction?].

PMID- 8251608
TI  - [Arthur Guedel].

PMID- 8251609
TI  - [Ambulatory epidural morphine analgesia via a transcutaneous implanted spinal
      catheter].
AB  - This report deals with a patient suffering from recurring rectum carcinoma
      infiltrating the lumbosacral plexus who received ambulant treatment with spinal
      opiate supply by a pump device, using a transcutaneous spinal catheter over a
      period of 12 weeks. The catheter turned out to be simple to implant. During the
      whole period no malfunctions occurred. This form of spinal analgesic treatment
      allowed the patient a relatively pain-free life outside the hospital.

PMID- 8251610
TI  - Intravenous verapamil kinetics in rats: marked arteriovenous concentration
      difference and comparison with humans.
AB  - The pharmacokinetics of verapamil, a calcium channel blocker, were studied in
      male Sprague-Dawley rats following i.v. administration at a dose of 1 mg kg-1.
      Both arterial and venous blood were collected and the plasma drug concentrations
      were determined by reversed-phase high-performance liquid chromatography.
      Verapamil was distributed to the extravascular tissues very rapidly as indicated
      by the large Vdss (2.99 +/- 0.57 l kg-1) and Vd beta (5.08 +/- 0.54 l kg-1). The
      apparent terminal plasma T1/2, MRTiv, and CLp were 1.59 +/- 0.46, 1.26 +/- 0.12
      h, and 40.4 +/- 9.73 ml min-1 kg-1, respectively. Marked arterial/venous
      differences were found with a considerable influence on the MRT and Vdss, and the
      terminal phase venous levels were higher than arterial levels by 103, 69, and
      90%, respectively, for the three rats studied. The distribution of verapamil
      between plasma and erythrocytes occurred very rapidly and was identical in vitro
      and in vivo. The average blood to plasma and plasma to blood cell concentration
      ratios were 0.85 and 1.47, respectively. In contrast to propranolol, blood data
      rather than plasma data should be used to predict the hepatic extraction ratio of
      verapamil (0.87). The plasma protein binding of verapamil in humans (90%) and
      rats (95%) were quite similar and constant over the wide concentration range
      studied. A comparison of some pharmacokinetic parameters between rats and humans
      is presented and the potential shortcomings of using T1/2 or CLp and the
      advantage of using CLu (unbound plasma clearance) in interspecies scaling is also
      discussed.

PMID- 8251611
TI  - Relationship between content of hepatic glutathione S-transferases and the
      kinetics of indocyanine green elimination in various liver diseases.
AB  - The glutathione (GSH) S-transferases are believed to have dual functions as
      hepatic detoxifying enzymes and intrahepatic binding proteins. Little is known
      about their alterations in human liver diseases. Therefore, we have studied the
      relationship between the enzyme activity and rose bengal (RB) binding in hepatic
      cytosol and plasma indocyanine green (ICG) kinetics in patients with various
      liver diseases. The enzyme activity was measured in samples of hepatic cytosol
      obtained from 52 patients. In addition, the content of cationic and neutral
      transferases was estimated in 17 biopsy samples by densitometry of Coomassie blue
      stained sodium dodecyl sulphate polyacrylamide gel electrophoretograms. RB
      binding studies also were performed on cytosol samples. ICG kinetic parameters
      were determined using the two-compartment open model in 17 patients who were
      given the dye (0.5 mg kg-1) intravenously. Correlations between the enzyme
      activity and liver function tests, content of the enzyme, RB binding and ICG
      kinetic parameters were evaluated. The following results were obtained. (1) The
      enzyme activities were high in alcoholic liver disease, fatty liver and Gilbert's
      syndrome, and low in cirrhosis. (2) The enzyme activities were positively
      correlated with serum cholinesterase activity, serum albumin level and
      hepaplastin test, and negatively correlated with ICG retention rate at 15 min.
      (3) The enzyme activity, its content and RB binding affinity of the cytosol were
      positively correlated with each other. (4) The enzyme activity was positively
      correlated with hepatic ICG distribution volume. These results are consistent
      with the role of the GSH S-transferases as ligandins in intracellular storage of
      dyes.

PMID- 8251612
TI  - Pharmacokinetics of intravenous and epidural ropivacaine in the rhesus monkey.
AB  - Ropivacaine is a new long-acting amide local anesthetic which is possibly less
      cardiotoxic than bupivacaine. The absorption and disposition of ropivacaine were
      characterized in six rhesus monkeys in an open two-way crossover study following
      intravenous and epidural administration. For these studies, animals were
      anesthetized for placement of intravenous and intraarterial catheters. For the
      epidural studies, a PE-10 catheter was also inserted 3 cm into the lumbar
      epidural space. After recovery from anesthesia, animals received ropivacaine 1 mg
      kg-1 intravenously over 1 min or 10 mg of ropivacaine epidurally (two 1 ml doses
      of 0.5%, 5 min apart), and arterial blood samples were obtained over 5 h. Serum
      ropivacaine concentrations were determined by gas chromatography with NP
      detection. Concentration-time data following i.v. and epidural administration
      were fitted simultaneously. Initial parameter estimates were obtained by
      analyzing each route separately. Input rates and their corresponding extent of
      absorption were estimated using deconvolution. Mean (+/- SD) disposition
      parameters included: Vss = 1.11 +/- 0.198 l kg-1; CL = 0.711 +/- 0.158 l h-1 kg
      1; t1/2,z = 2.07 +/- 0.438 h. Mean (+/- SD) absorption parameters included: F1 =
      0.506 +/- 0.221; t1/2,kal = 0.060 +/- 0.078 h; F2 = 0.444 +/- 0.182; t1/2,ka2 =
      6.45 +/- 11.09 h. Ropivacaine's biphasic absorption and bioavailability are
      similar to those of other amide local anesthetics. The biphasic absorption may be
      related to partitioning into fat or regional changes in blood flow induced by the
      drug.

PMID- 8251613
TI  - Pharmacokinetics of oral L-isoidide mononitrate in rats.
AB  - L-isoidide mononitrate (L-IIMN) is the most potent mononitrate vasodilator
      described so far in the literature. Since other mononitrates, such as isosorbide
      5-mononitrate and isosorbide-2-mononitrate, have been shown not to be subject to
      first-pass metabolism, we examined the pharmacokinetics of L-IIMN after oral
      administration to determine whether this compound also exhibited this behavior.
      An oral dose of 2 mg kg-1 L-IIMN dissolved in normal saline was given to seven
      rats. Absorption of L-IIMN after dosing was rapid with an apparent absorption
      half-life of 9.5 +/- 3.6 min (mean +/- SD). Plasma L-IIMN concentrations peaked
      between 5 and 20 min after dosing and declined thereafter in an apparently
      monoexponential manner. The average elimination half-life was 11.9 +/- 1.7 min
      (mean +/- SD). Oral bioavailability was estimated to be about 50%. Thus, unlike
      the other mononitrates so far examined in the literature, L-IIMN exhibits
      incomplete bioavailability. This pharmacokinetic behavior, however, is consistent
      with its faster systemic clearance compared to other organic mononitrates.

PMID- 8251614
TI  - Kinetic analysis of tissue distribution of doxorubicin incorporated in liposomes
      in rats (II).
AB  - The objective of this study is to perform kinetic modelling of the tissue
      distribution of doxorubicin encapsulated into liposomes (L-DXR), especially to
      the heart and liver. The release process of doxorubicin (DXR) from liposomes in
      blood was quantified by a release clearance. This parameter defines a release
      rate of DXR based on the concentration of L-DXR in blood and was estimated from
      kinetic modelling of DXR distribution to the heart after L-DXR administration.
      The distribution of free DXR to the heart was modelled separately. The
      experimental data for this modelling were reported previously (Harashima et al.,
      Biopharm. Drug. Disposit., 13, 155-170 (1992)). This analysis provided a free DXR
      concentration profile as well as a release clearance of DXR after L-DXR
      administration. There was a remarkable difference in the free DXR concentration
      in blood between free and liposomal administration. The area under the DXR curve
      in the heart was reduced by approximately one third from that for the first two
      hours after DXR administration by liposomal encapsulation, which could be the
      reason for reduced cardiac toxicity. In our previous report, the distribution of
      L-DXR to the liver was shown to be explained by a sequentially linked two
      compartment model with efflux process. The validity of this efflux model was
      examined in this study by a repeated dose study. The apparent uptake clearance
      decreased with time and showed a second peak after the repeated dose, which
      justified the efflux model. These kinetic analyses give quantitative
      understanding of the effect of liposomal encapsulation on the tissue distribution
      of DXR.

PMID- 8251615
TI  - Pharmacokinetic profiles of glycyrrhizin in patients with chronic hepatitis.
AB  - The pharmacokinetics of glycyrrhizin (G) in eight patients with chronic hepatitis
      receiving chronically i.v. administration of 120 mg dose of G was investigated.
      The plasma concentration of G in the patients after dosing declined in a
      monophasic manner. However, the pharmacokinetic profiles varied among patients.
      The mean elimination half-life (t1/2) and the total body clearance (CLtot) were
      6.0 h (range 4.3-10.7 h) and 7.9 ml h-1 kg-1 (4.5-12.7 ml h-1 kg-1),
      respectively. The variation of the CLtot for G was closely related to that of
      aspartate aminotransferase (r = -0.739, p < 0.05) and alanine aminotransferase (r
      = -0.783, p < 0.05) activities in the plasma.

PMID- 8251616
TI  - Cyclosporin A and erythromycin: a study of a drug interaction in the in situ
      perfused rat liver model.
AB  - Using the in situ perfused rat liver model, the effect of erythromycin (Ery) on
      the disposition of cyclosporin A (CyA) and the major human metabolite, AM1, was
      investigated. Prior to perfusion experiments, oral dosing was carried out for
      three days on three groups of male Sprague-Dawley rats (300-350 g), involving
      pretreatment with water (control and H2O/Ery groups) or erythromycin (Ery oral
      group). On the fourth day, perfusion experiments took place using standard
      techniques, with the addition of 20 mg Ery to the H2O/Ery and Ery oral groups,
      and 2.5 mg CyA to all groups. Perfusate and bile samples were collected and
      assayed for CyA and AM1 by HPLC. Results indicated that inhibition of CyA
      metabolism had occurred as the CyA concentration in perfusate was significantly
      higher in both Ery groups at all times compared to the control group, and the
      levels of AM1 in both perfusate and bile were significantly lower than in the
      control group. There was also a marked reduction in the apparent metabolic
      clearance of CyA in the Ery groups. It was concluded that AM1 production had been
      inhibited by Ery, the most likely mechanism being inhibition of the isoenzyme
      CYP3A with which Ery forms a stable complex.

PMID- 8251617
TI  - Influence of albumin on isoprenaline and propranolol effects on isolated rat
      uterus.
AB  - We investigated the effect of albumin (6%) on the (+/-)-isoprenaline-induced
      relaxation of strips of isolated rat uterus and its antagonism by (-)
      propranolol. The mean isoprenaline EC50 in the presence of albumin was
      significantly less than that in the absence of albumin (geometric mean 1.94 +/-
      3.33 versus 3.21 +/- 3.50 nM, respectively; n = 14; p = 0.006, paired t test).
      This indicates enhancement of isoprenaline activity by albumin which could not be
      explained by protein binding, as this would have reduced activity. Geometric mean
      control KB values for inhibition of isoprenaline by propranolol at 26.8 and 500
      nM were 0.835 +/- 1.68 (n = 10) and 0.889 +/- 1.60 nM (n = 34), respectively. In
      the presence of 6% albumin, KB for propranolol was increased significantly to
      13.3 +/- 1.8 nM (n = 27, p < 0.001). Calculation of KB in terms of the measured
      propranolol unbound concentration of 26.8 nM, after taking into account the lower
      isoprenaline EC50 in the presence of albumin, yielded a mean value of 0.725 +/-
      1.86 nM, which was not significantly different from either control (p > 0.05).
      Therefore, propranolol activity was as predicted by the unbound drug
      concentration in contrast to isoprenaline activity. We conclude that albumin can
      alter in vitro drug activity by mechanisms in addition to the reduction of
      unbound drug concentration.

PMID- 8251618
TI  - A method for calculating the mean transit times and distribution rate parameters
      of interconversion metabolites.

PMID- 8251619
TI  - Proof of the independence of the AUC and the absorption rate.

PMID- 8251620
TI  - SequAlign: a computer program that displays DNA sequence alignments as a compact
      'bar-code' graph.

PMID- 8251621
TI  - Transient and stable expression of gusA fusions with rice genes in rice, barley
      and perennial ryegrass.
AB  - Transcriptional and translational fusions were made between the reading frame
      coding for beta-D-glucuronidase and sequences of either a constitutively
      expressed rice gene (GOS2) involved in initiation of translation or a light
      inducible rice gene (GOS5). The transient expression of the fusions was studied
      via particle bombardment of seedling tissues of rice, perennial ryegrass and
      barley. Furthermore, the results of transient and stable expression were compared
      for cell suspensions of four rice varieties, one barley variety and one perennial
      ryegrass variety. The GOS2-gusA fusions were active in all three monocots
      studied. Best results were obtained for a construct having both a transcriptional
      and a translational fusion as well as intron and exon sequences (PORCEHyg). The
      level of GUS activity was in the range of activities as obtained by the 35S CaMV
      promoter transcriptionally fused to gusA. The gusA fusion with the light
      inducible gene (GOS5) was active in green seedling tissues of all monocots
      studied. Also a weak expression compared to the GOS2 constructs was found in
      stably transformed rice callus. The gusA fusions with the mannopine synthase
      promoters 1' and 2' of the TR-DNA were transiently expressed at lower levels in
      cell suspensions than PORCEHyg. For stably transformed rice callus the expression
      of the GOS2-gusA fusion often decreased during prolonged subculture. This
      decrease in GUS activity and the various GUS-staining phenotypes of transgenic
      calli are explained by the presence of different cell types in the suspensions
      used and in the calli. It is presumed that the nature of the cells and their
      relative contribution in the calli change drastically upon further subculture.

PMID- 8251622
TI  - Deletion analysis of a 2S seed storage protein promoter of Brassica napus in
      transgenic tobacco.
AB  - The promoter and upstream region of the Brassica napus 2S storage protein napA
      gene were studied to identify cis-acting sequences involved in developmental seed
      specific expression. Fragments generated by successive deletions of the 5'
      control region of the napA gene were fused to the reporter gene beta
      glucuronidase (GUS). These constructs were used to transform tobacco leaf discs.
      Analyses of GUS activities in mature seeds from the transformed plants indicated
      that there were both negatively and positively acting sequences in the napin gene
      promoter. Deletion of sequences between -1101 and -309 resulted in increased GUS
      activity. In contrast, deletion of sequences between -309 and -211 decreased the
      expression. The minimum sequence required for seed-specific expression was a 196
      bp fragment between -152 and +44. Further 5' deletion of the fragment to -126
      abolished this activity. Sequence comparison showed that a G box-like sequence
      and two sequence motifs conserved between 2S storage protein genes are located
      between -148 to -120. Histochemical and fluorometric analysis of tobacco seeds
      showed that the spatial and developmental expression pattern was retained in the
      deletion fragments down to -152. However, the expression in tobacco seeds
      differed from the spatial and temporal expression in B. napus. In tobacco, the
      napA promoter directed GUS activity early in the endosperm before any visible
      activity could be seen in the heart-shaped embryo. Later, during the transition
      from heart to torpedo stages, the main expression of GUS was localized to the
      embryo. No significant GUS activity was found in either root or leaf.

PMID- 8251623
TI  - Molecular characterization of maize extensin expression.
AB  - This study concerned the developmental regulation of wall-localized,
      hydroxyproline-containing proteins in maize tissues and organs. Silk and pericarp
      cell walls contained more peptidyl hydroxyproline than did walls of any
      vegetative tissue, although all tissues and organs accumulated these proteins as
      they matured. In many tissues, hydroxyproline-rich proteins are first associated
      with the wall in a soluble form before being insolubilized through covalent
      attachment to the matrix. Because hydroxyproline was more soluble earlier than
      later in development, it appears that insolubilization was occurring in maize
      tissues and organs as well. Tissue prints reacted with an anti-extensin antibody
      gave positive results, indicating the presence of a soluble form of this common
      hydroxyproline-rich glycoprotein (HRGP). Silk and pericarp cells actively
      synthesized this extensin from abundant transcripts. In vegetative tissues,
      extensin transcripts were somewhat more abundant in seedlings than in pre
      anthesis or mature plants, but levels were much lower than in silk and pericarp.
      Southern blots of maize genomic DNA indicated that these extensin transcripts are
      encoded by a small multigene family. Potential roles for extensin in
      reproductive/protective tissues versus the embryo or vegetative tissues are
      suggested.

PMID- 8251625
TI  - Precursors of one integral and five lumenal thylakoid proteins are imported by
      isolated pea and barley thylakoids: optimisation of in vitro assays.
AB  - In vitro assays for the import of proteins by isolated pea thylakoids have been
      refined and optimised with respect to (a) the method of thylakoid preparation,
      (b) the concentration of thylakoids in the import assay, and (c) the pH and
      temperature of the import assay. As a result, the 23 kDa and 16 kDa proteins of
      the photosynthetic oxygen-evolving complex are imported with efficiencies
      approaching 100%; import of the third oxygen-evolving complex protein is also
      observed, albeit with lower efficiencies. We have also demonstrated import of
      three further thylakoid proteins: plastocyanin, the CFoII subunit of the ATP
      synthase, and the photosystem I subunit, PSI-N, using this import assay. Import
      of plastocyanin, PSI-N and the 33 kDa oxygen-evolving complex protein subunit
      requires the presence of stromal extract whereas the other three proteins are
      efficiently imported in the absence of added soluble proteins. Import into
      isolated barley thylakoids was achieved under identical assay conditions,
      although with somewhat lower efficiency than into pea thylakoids.

PMID- 8251624
TI  - Differential expression of tomato (Lycopersicon esculentum L.) genes encoding
      shikimate pathway isoenzymes. II. Chorismate synthase.
AB  - In tomato (Lycopersicon esculentum L. cv. UC82b) two distinct genes (designated
      LeCS1 and LeCS2) code for chorismate synthase. The corresponding cDNAs have been
      isolated and characterized. The deduced amino acid sequences are 88% identical.
      Both genes encode chorismate synthases with putative plastid-specific N-terminal
      transit peptides. The two genes are predominantly expressed in flowers and roots
      and, to a lesser extent, in stems, leaves, and cotyledons, but the steady-state
      levels of LeCS1-specific transcripts are consistently higher than those of the
      LeCS2-specific transcripts.

PMID- 8251626
TI  - A tRNA(Val) (GAC) gene of chloroplast origin in sunflower mitochondria is not
      transcribed.
AB  - A tRNA(Val) (GAC) gene is located in opposite orientation 552 nucleotides (nt)
      down-stream of the cytochrome oxidase subunit III (coxIII) gene in sunflower
      mitochondria. The comparison with the homologous chloroplast DNA revealed that
      the tRNA(Val) gene is part of a 417 nucleotides DNA insertion of chloroplast
      origin in the mitochondrial genome. No tRNA(Val) is encoded in monocot
      mitochondrial DNA (mtDNA), whereas two tRNA(Val) species are coded for by potato
      mtDNA. The mitochondrial genomes of different plant species thus seem to encode
      unique sets of tRNAs and must thus be competent in importing the missing
      differing sets of tRNAs.

PMID- 8251627
TI  - Metabolic regulation of alpha-amylase gene expression in transgenic cell cultures
      of rice (Oryza sativa L.).
AB  - Expression of two genes in the alpha-amylase gene family is controlled by
      metabolic regulation in rice cultured cells. The levels of RAmy3D and RAmy3E
      mRNAs in rice cultured cells are inversely related to the concentration of sugar
      in the culture medium. Other genes in the rice alpha-amylase gene family have
      little or no expression in cultured cells; these expression levels are not
      controlled by metabolic regulation. A RAmy3D promoter/GUS gene fusion was
      metabolically regulated in the transgenic rice cell line 3DG, just as the
      endogenous RAmy3D gene is regulated. An assay of GUS enzyme activity in 3DG cells
      demonstrated that RAmy3D/GUS expression is repressed when sugar is present in the
      culture medium and induced when sugar is removed from the medium. The 942 bp
      fragment of the RAmy3D promoter that was linked to the coding region of the GUS
      reporter gene thus contains all of the regulatory sequences necessary for
      metabolic regulation of the gene.

PMID- 8251628
TI  - Constitutive or light-regulated expression of the rolC gene in transgenic potato
      plants has different effects on yield attributes and tuber carbohydrate
      composition.
AB  - Tetraploid potato clones, transgenic for the rolC gene of Agrobacterium
      rhizogenes under control of the light-inducible ribulose bisphosphate carboxylase
      small subunit promoter (rbcS-rolC), were compared, with respect to yield
      attributes and tuber carbohydrates, with transformed and untransformed controls
      and with 35S-rolC transgenic potato plants. In rbcS-rolC plants, the expression
      of the rolC gene was located mainly in leaves, while in 35S-rolC plant
      transcripts were detected as well in shoots and roots. Phenotypically, rbcS-rolC
      transgenic plants were found to be slightly reduced in plant size with a few more
      tillers than control plants. Photosynthetic rate and chlorophyll content were
      significantly lower in all rolC transgenic plants irrespective of the type of
      construct used. Tuber yield was not significantly different between controls and
      rbcS-rolC transgenic plants, but was reduced in the 35S-rolC transformants.
      Sucrose level was unchanged in all rolC clones investigated, whereas fructose
      content was significantly enhanced in 35S-rolC transformants, but not in the
      plants expressing the rolC gene in aerial plant parts only. In both types of rolC
      transgenic plants, glucose content was lower than in controls, resulting in a
      significant reduction of reducing sugar in tubers. The results suggest a hormonal
      influence on the carbohydrate composition of potato tubers.

PMID- 8251629
TI  - Concerted regulation of lysine and threonine synthesis in tobacco plants
      expressing bacterial feedback-insensitive aspartate kinase and
      dihydrodipicolinate synthase.
AB  - The essential amino acids lysine and threonine are synthesized in higher plants
      by two separate branches of a common pathway. This pathway is primarily regulated
      by three key enzymes, namely aspartate kinase (AK), dihydrodipicolinate synthase
      (DHPS) and homoserine dehydrogenase (HSD), but how these enzymes operate in
      concert is as yet unknown. Addressing this issue, we have expressed in transgenic
      tobacco plants high levels of bacterial AK and DHPS, which are much less
      sensitive to feedback inhibition by lysine and threonine than their plant
      counterparts. Such expression of the bacterial DHPS by itself resulted in a
      substantial overproduction of lysine, whereas plants expressing only the
      bacterial AK overproduced threonine. When both bacterial enzymes were expressed
      in the same plant, the level of free lysine exceeded by far the level obtained by
      the bacterial DHPS alone. This increase, however, was accompanied by a
      significant reduction in threonine accumulation compared to plants expressing the
      bacterial AK alone. Our results suggested that in tobacco plants the synthesis of
      both lysine and threonine is under a concerted regulation exerted by AK, DHPS,
      and possibly also by HSD. We propose that the balance between lysine and
      threonine synthesis is determined by competition between DHPS and HSD on limiting
      amounts of their common substrate 3-aspartic semialdehyde, whose level, in turn,
      is determined primarily by the activity of AK. The potential of this molecular
      approach to increase the nutritional quality of plants is discussed.

PMID- 8251630
TI  - Isolation and characterization of two Brassica napus embryo acyl-ACP thioesterase
      cDNA clones.
AB  - Acyl-ACP thioesterases are involved in regulating chain termination of fatty acid
      biosynthesis in plant systems. Previously, acyl-ACP thioesterase purified from
      Brassica napus seed tissue has been shown to have a high preference for
      hydrolysing oleoyl-ACP. Here, oligonucleotides derived from B. napus oleoyl-ACP
      thioesterase protein sequence data have been used to isolate two acyl-ACP
      thioesterase clones from a B. napus embryo cDNA library. The two clones, pNL2 and
      pNL3, contain 1642 bp and 1523 bp respectively and differ in the length of their
      3' non-coding regions. Both cDNAs contain open reading frames of 366 amino acids
      which encode for 42 kDa polypeptides. Mature rape thioesterase has an apparent
      molecular weight of 38 kDa on SDS-PAGE and these cDNAs therefore encode for
      precursor forms of the enzyme. This latter finding is consistent with the
      expected plastidial location of fatty acid synthase enzymes. Northern blot
      analysis shows thioesterase mRNA size to be ca. 1.6 kb and for the thioesterase
      genes to be highly expressed in seed tissue coincident with the most active phase
      of storage lipid synthesis. There is some sequence heterogeneity between the two
      cDNA clones, but overall they are highly homologous sharing 95.7% identity at the
      DNA level and 98.4% identity at the amino acid level. Some sequence heterogeneity
      was also observed between the deduced and directly determined thioesterase
      protein sequences. Consistent with the observed sequence heterogeneity was
      Southern blot data showing B. napus thioesterase to be encoded by a small multi
      gene family.

PMID- 8251631
TI  - Analysis of soybean chloroplast DNA replication by two-dimensional gel
      electrophoresis.
AB  - Chloroplast DNA replication was studied in the green, autotrophic suspension
      culture line SB-1 of Glycine max. Three regions (restriction fragments Sac I
      14.5, Pvu II 4.1 and Pvu II 14.8) on the plastome were identified that displayed
      significantly higher template activity in in vitro DNA replication assays than
      all other cloned restriction fragments of the organelle genome, suggesting that
      these clones contain sequences that are able to direct initiation of DNA
      replication in vitro. In order to confirm that the potential in vitro origin
      sites are functional in vivo as well, replication intermediates were analyzed by
      two-dimensional gel electrophoresis using cloned restriction fragments as probes.
      The two Pvu II fragments that supported deoxynucleotide incorporation in vitro
      apparently do not contain a functional in vivo replication origin since
      replication intermediates from these areas of the plastome represent only fork
      structures. The Sac I 14.5 chloroplast DNA fragment, on the other hand, showed
      intermediates consistent with a replication bubble originating within its
      borders, which is indicative of an active in vivo origin. Closer examination of
      cloned Sac I 14.5 sub-fragments confirmed high template activity in vitro for
      two, S/B 5 and S/B 3, which also seem to contain origin sites utilized in vivo as
      determined by two-dimensional gel electrophoresis. The types of replication
      intermediate patterns obtained for these sub-fragments are consistent with the
      double D-loop model for chloroplast DNA replication with both origins being
      located in the large unique region of the plastome [17, 18]. This is the first
      report of a chloroplast DNA replication origin in higher plants that has been
      directly tested for in vivo function.

PMID- 8251632
TI  - Cytosine deaminase as a negative selective marker for Arabidopsis.
AB  - Cytosine deaminase (CD), produced by prokaryotes but not by higher eukaryotes
      including plants, deaminates cytosine to uracil. The enzyme likewise converts 5
      fluorocytosine (5FC), which by itself is not toxic, to 5-fluorouracil (5FU),
      which is toxic. The Escherichia coli codA-coding sequence encoding CD, together
      with appropriate regulatory elements, was introduced into Arabidopsis. Neither
      untransformed controls, nor transgenic plants expressing no CD mRNA, were
      sensitive to 5FC. Conversely, for most transgenic plants expressing CD mRNA, in
      the presence of 5FC calli and seedlings failed to proliferate, and seeds failed
      to germinate. A few transgenic plants with many codA copies expressed less CD
      mRNA and remained insensitive to 5FC, which likely reflected epigenetic repeat
      induced gene silencing. Thus 5FC, presumably through conversion by the enzyme to
      5FU, can be used to select against plants that express CD.

PMID- 8251633
TI  - Characterization of a genomic sequence coding for potato multicystatin, an eight
      domain cysteine proteinase inhibitor.
AB  - A gene coding for potato multicystatin (PMC), the crystalline inhibitor of
      cysteine proteases which is found in tubers, was isolated and characterized. The
      deduced polypeptide product of this genomic sequence is 757 amino acids long and
      has a molecular mass of 86,778 Da. It consists exclusively of eight closely
      related domains, with 53-89% identity of residues. Each repeated unit is
      homologous to the cystatin superfamily of cysteine protease inhibitors. To date,
      no other member of this family has been found to contain so many inhibitor
      domains in one polypeptide. Eight introns are proposed in the 3.5 kb of genomic
      DNA coding for PMC, one in each cystatin unit. There is a family of 4 to 6 such
      large genes in potato, while in pea and maize the homologues are much smaller,
      and probably code for single-domain cystatins. PMC transcripts are abundant in
      tubers, but scarce in undamaged leaves or stems of field-grown potatoes. The
      tuber messages are derived from at least four genes (including the cloned
      example). The pattern of gene expression, as well as the properties of the
      protein, suggest that PMC has a role in the plant's defense system.

PMID- 8251634
TI  - Abundance of an mRNA encoding a high mobility group DNA-binding protein is
      regulated by light and an endogenous rhythm.
AB  - A cDNA clone encoding an HMG1 protein from Pharbitis nil was characterized with
      regard to its sequence, genomic organization and regulation in response to
      photoperiodic treatments that control floral induction. The HMG1 cDNA contains an
      open reading frame of 432 nucleotides encoding a 144 amino acid protein of
      approximately 16 kDa. The predicted polypeptide has the characteristic conserved
      motifs of the HMG1 and HMG2 class of proteins including an N-terminal basic
      region, one of two HMG-box domains, and a polyacidic carboxy terminus. Within the
      HMG-box region, Pharbitis HMG1 deduced amino acid sequence shares 47%, 67% and
      69% identity with its animal, maize, and soybean counterparts, respectively.
      Southern blot hybridization analysis suggests that HMG1 is a member of a
      multigene family. Analysis of mRNA abundance indicates that the HMG1 gene is
      expressed to higher levels in dark-grown tissue, such as roots, and at lower
      levels in light-grown tissue, such as cotyledons and stems. Following the
      transition to darkness, the levels of HMG1 mRNA in cotyledons were initially
      stable, however, after a lag time of 8 h or more, HMG1 mRNA increased in
      abundance to a peak level at 20 h. A second peak in mRNA levels was observed
      about 24 h later, indicating that the expression of the HMG1 gene is regulated by
      an endogenous circadian rhythm. Abundance of the HMG1 mRNA during a dark period
      was dramatically affected by brief light exposure (night break), a treatment
      which inhibits floral induction. These data indicate that the expression of HMG1
      is regulated by both an endogenous rhythm and the light/dark cycle and are
      consistent with a role for HMG1 in maintaining patterns of circadian-regulated
      gene expression activated upon the transition from light to darkness.

PMID- 8251635
TI  - The origin of lysine-containing proteins in opaque-2 maize endosperm.
AB  - The reduction of zein synthesis in the maize (Zea mays L.) opaque-2 mutant is
      associated with an increased percentage of lysine in the endosperm protein. When
      expressed on an endosperm basis, we found that W64A opaque-2 contains 490
      micrograms of lysine compared with 350 micrograms in W64A normal. SDS-PAGE
      analysis of endosperm proteins indicated that several non-zein proteins are more
      abundant in the mutant than in normal genotype. To determine the subcellular
      origin of these proteins, we separated an endosperm homogenate from developing
      kernels by sucrose density gradient centrifugation and used marker enzyme assays
      and immunoblot analyses to identify cellular components. Amino acid analysis of
      proteins in the gradient fractions showed that the majority of the lysine occurs
      in soluble proteins at the top of the gradient. To identify these proteins, we
      prepared a complex antiserum against the entire soluble protein fraction and used
      it to immunoscreen an endosperm cDNA expression library. Sequence analysis of
      clones identified mRNAs involved in carbohydrate metabolism, amino acid
      biosynthesis, and protein synthesis. RNA dot blot hybridization analysis with
      these clones revealed significant variation in the levels of transcripts between
      normal and opaque-2 endosperm, but we identified several mRNAs that are elevated
      in opaque-2 and that may encode proteins responsible for the enhanced lysine
      content.

PMID- 8251636
TI  - Isolation, sequencing and analysis of the expression of Bryonia calmodulin after
      mechanical perturbation.
AB  - A cDNA clone (Bc329) encoding calmodulin was isolated from a Bryonia cDNA library
      by screening with cloned Arabidopsis calmodulin cDNA. The cDNA Bc329 was 899 bp
      full-length clone. The predicted amino acid sequence consists of 149 residues and
      reveals a high homology with other known plant calmodulins (91 to 99% identity).
      Genomic southern blot suggests that Bryonia calmodulin is encoded by a single
      copy gene. The Bc329 clone was used as a probe to study the expression of
      calmodulin mRNA after a mechanical stimulus applied on young Bryonia internodes.
      The steady-state of calmodulin mRNA reached a maximum 30 min after the treatment
      before it progressively decreased. The role of calcium and calmodulin as second
      messengers is discussed with regard to environmental changes.

PMID- 8251637
TI  - Single-copy T-DNA insertions in Arabidopsis are the predominant form of
      integration in root-derived transgenics, whereas multiple insertions are found in
      leaf discs.
AB  - Different patterns of T-DNA integration in Arabidopsis were obtained that
      depended on whether a root or a leaf-disc transformation method was used. An
      examination of 82 individual transgenic Arabidopsis plants, derived from 15
      independent Agrobacterium-mediated transformations in which different cointegrate
      and binary constructs were used, indicated that the transformation method had a
      significant influence on the type and copy number of T-DNA integration events.
      Southern hybridizations showed that most of the transgenic plants produced by a
      leaf-disc method contained multiple T-DNA insertions (89%), the majority of which
      were organized as right-border inverted repeat structures (58%). In contrast, a
      root transformation method mostly resulted in single T-DNA insertions (64%), with
      fewer right-border inverted repeats (38%). The transformation vectors, including
      cointegrate and binary types, and the plant selectable markers, hygromycin
      phosphotransferase and dihydrofolate reductase, did not appear to influence the T
      DNA integration patterns.

PMID- 8251638
TI  - Secretion of a functional single-chain Fv protein in transgenic tobacco plants
      and cell suspension cultures.
AB  - A synthetic gene encoding an anti-phytochrome single-chain Fv (scFv) antibody
      bearing an N-terminal signal peptide has been used to transform tobacco plants.
      Immunoblot analysis showed that transformed plants accumulate high levels of scFv
      protein, accounting for up to 0.5% of the total soluble protein fraction, which
      could be extracted by simple infiltration and centrifugation of leaf tissue. A
      substantial proportion of the scFv protein extracted in this way was found to
      possess antigen-binding activity. Callus cell suspension cultures derived from
      transformed plants secrete functional scFv protein into the surrounding medium.
      Compared with the levels of scFv protein observed in plants expressing the native
      scFv gene, the incorporation of an N-terminal signal peptide, to target the scFv
      to the apoplast, results in elevated accumulation of the protein.

PMID- 8251639
TI  - Molecular analysis and spatial expression pattern of a low-temperature-specific
      barley gene, blt101.
AB  - A cDNA clone of the previously unreported low-temperature-induced gene blt101 was
      isolated after a differential screen of a cDNA library prepared from low
      temperature (6 degrees C day/2 degrees C night) grown barley shoot meristems.
      Southern blot analysis of barley ditelosomic addition lines was used to assign
      this single-copy gene to the long arm of chromosome 4. Analysis of steady-state
      levels of blt101 mRNA showed the induction of this transcript in shoot meristems
      upon transfer of barley (cv. Igri) plants from control (20 degrees C/15 degrees
      C) to low (6 degrees C/2 degrees C) temperature treatment. Further, the high
      level of this transcript is maintained at low temperatures but is reduced on
      transfer from low to control temperatures. The gene is not induced by drought or
      by foliar application of ABA. Analysis of segregating doubled haploid lines shows
      that there is no specific association of this gene with either spring/winter
      growth habit or frost hardiness. Examination of the spatial expression pattern
      revealed ubiquitous expression of blt101 in low-temperature (6 degrees C/2
      degrees C) grown barley shoot meristems, mature leaves and roots.

PMID- 8251640
TI  - Cloning, sequence analysis and expression of a cDNA encoding active
      phosphoenolpyruvate carboxylase of the C3 plant Solanum tuberosum.
AB  - A cDNA coding for phosphoenolpyruvate carboxylase (PEPC) was isolated from a cDNA
      library from Solanum tuberosum and the sequence of the cDNA was determined. It
      was inserted into a bacterial expression vector and a PEPC- Escherichia coli
      mutant could be complemented by the cDNA construct. A functional fusion protein
      could be synthesized in E. coli. The properties of this PEPC protein clearly
      resembled those of typical C3 plant enzymes.

PMID- 8251641
TI  - Cell-type specific expression of three rice genes GOS2, GOS5 and GOS9.
AB  - The cell-type-specific expression of three rice genes, GOS2, GOS5 and GOS9, was
      studied by mRNA in situ hybridization. Previous northern blot analysis revealed
      that these genes were constitutive, green tissue-specific and root-specific,
      respectively. In this study, GOS2 transcripts were observed in all leaf cell
      types. In roots, a temporal and spatial expression pattern was noticed. Higher
      mRNA levels were observed in lateral roots, especially in parenchymal cells of
      the vascular cylinder. Expression of GOS5 was mainly found in chloroplast
      containing cells. For GOS9, significant levels of signal were observed in root
      and leaf sections.

PMID- 8251642
TI  - Stable assembly of PsaE into cyanobacterial photosynthetic membranes is dependent
      on the presence of other accessory subunits of photosystem I.
AB  - We studied assembly of the PsaE subunit of photosystem I into photosynthetic
      membranes of cyanobacterial mutant strains that lack specific photosystem I
      subunits. Radiolabeled PsaE was incubated with photosynthetic membranes, and
      their binding and assembly were assayed by resistance to removal by chaotropic
      agents and proteolytic digestion. PsaE incorporated into the wild-type membranes
      was resistant to these treatments. In the absence of PsaD, it was resistant to
      proteolytic digestion, but was removed by NaBr. When the membranes were isolated
      from a mutant strain in which the psaF and psaJ genes have been inactivated, PsaE
      assembled in vitro could not be removed. PsaE could associate with the membranes
      of the strain DF in which the psaD, psaJ and psaF genes have been mutated.
      However, the radiolabeled PsaE associated with these membranes was removed both
      by the proteolytic as well as by the chaotropic agents. Characterization of PsaE
      present in vivo revealed similar results. These observations suggest that PsaD
      and PsaF/J may interact with PsaE and stabilize it in the photosystem I complex.

PMID- 8251643
TI  - Nucleotide sequence of a flower-specific MADS box cDNA clone from orchid.
AB  - An orchid (Aranda deborah) mature flower cDNA library was screened with an
      agamous cDNA probe from Arabidopsis. One positive clone for agamous gene was
      isolated, cloned and sequenced. This cDNA clone (om1) has a full length open
      reading frame of 750 bp corresponding to 250 amino acid residues. Comparison of
      om1 MADS box with that of its counterparts in tomato and Arabidopisis reveals
      significantly high homology (> 95%). Northern analysis indicated this gene is
      expressed in mature flowers and not in young developing inflorescences or young
      floral buds. In the mature flowers, it is only expressed in petals and weakly in
      sepals but not in the column (gynostemium).

PMID- 8251644
TI  - A conjugative plasmid vector for promoter analysis in several cyanobacteria of
      the genera Synechococcus and Synechocystis.
AB  - A promoter-probe vector, pSB2A, based on the plasmid RSF1010 and the promoterless
      chloramphenicol acetyl transferase (cat) reporter gene, has been constructed.
      pSB2A appeared to be most efficiently transferred by conjugation to the widely
      used cyanobacteria Synechocystis strains PCC6803 (S.6803) and PCC6714 (S.6714)
      and Synechococcus strains PCC7942 (S.7942) and PCC6301 (S.6301), where it
      replicates stably even though it contains no cyanobacterial DNA. Using pSB2A we
      found that (1) a light-regulated promoter from S.6803 remains controlled by light
      intensity in S.7942 while it is silent in Escherichia coli, and (2) the E. coli
      tac promoter behaves as a strong and light-independent promoter in the four
      cyanobacterial hosts tested.

PMID- 8251645
TI  - Cloning and characterization of a cDNA encoding the cytosolic copper/zinc
      superoxide dismutase from sweet potato tuberous root.
AB  - A full-length cDNA clone encoding a putative copper/zinc-superoxide dismutase
      (SOD) of sweet potato, Ipomoea batatas (L.) Lam. cv Tainong 57, was isolated from
      a cDNA library constructed in lambda gt10 from tuber root mRNA. Nucleotide
      sequence analysis of this cDNA clone revealed that it comprises a complete open
      reading frame coding for 152 amino acid residues. The deduced amino acid sequence
      showed higher homology (78-86%) with the sequence of the cytosolic SOD than that
      of the chloroplast SOD from other plant species. The residues required for
      coordinating copper and zinc are conserved as they are among all reported Cu/Zn
      SOD sequences. In addition, it lacks recognizable plastic or mitochondrial
      targeting sequences. These data suggest that the isolated sweet potato clone
      encodes a cytosolic Cu/Zn-SOD.

PMID- 8251646
TI  - Dietary habits and mammographic patterns in patients with breast cancer.
AB  - Between 1983 and 1986, dietary history interviews were conducted with 238 women
      aged 50-65 years who had surgery for stage I-II breast cancer. Diagnostic
      mammograms were coded in line with Wolfe's criteria in N1, P1, P2, and Dy
      patterns. Women with Dy pattern reported significantly higher intake of total
      fat, monounsaturated fatty acids (FA), polyunsaturated FA, n-3 FA, n-6 FA in per
      cent of energy (E%), and alpha-tocopherol in mg/10 MJ. Fat intake was lowest in
      women with N1 pattern and highest in those having Dy pattern. Patients having ER
      rich cancers and Dy pattern reported significantly higher intake of total fat,
      monounsaturated FA, polyunsaturated FA, n-6 FA (E%), and alpha-tocopherol (mg/10
      MJ), as well as significantly lower intake of carbohydrate (E%) and calcium (g/10
      MJ). In the stepwise multivariate analysis, the multivariate-odds ratio (OR) for
      having P2 + Dy patterns was 1.06 (95% confidence interval (CI), 1.02-1.12) for
      each increment in E% of total fat. In women with ER-rich tumors this OR was 1.09
      (95% CI, 1.02-1.16). The highest self-reported body mass index (BMI) was observed
      in women with N1 + P1 patterns. OR for having P2 + Dy patterns was 0.91 (95% CI,
      0.83-0.98) for each increment in 1 kg/m2 of BMI. The results suggest that dietary
      habits affect the mammographic parenchymal pattern in women with breast cancer
      and that a high fat intake is associated with a higher proportion of mammograms
      with Dy pattern in such patients.

PMID- 8251647
TI  - Prognostic significance of p53 gene alterations in node-negative breast cancer.
AB  - Mutations in the p53 gene can play a role in the transformation of normal to
      malignant cells. Because these mutations are more frequently reported later in
      the course of transformation, their presence could reflect a greater malignant
      potential of the tumor and, thus, an increased probability of metastasis and
      recurrence after local therapy. In a pilot study using single-stranded
      conformation polymorphism analysis (SSCP), 200 node-negative breast tumors were
      examined for mutations in the region encompassing exons 5 through 9 of the p53
      gene. Exons 5 through 9 were tested because they contain 80-90% of known p53 gene
      mutations. The tumors ranged in size from 1 to 3 cm. 28 tumors were found to have
      an abnormal band pattern on both initial and repeat analysis. 4 of these tumors
      were sequenced; 3 contained a p53 mutation and the 4th had a rare neutral
      polymorphism. Disease-free survival (DFS) at 5 years for women with tumors having
      an abnormal SSCP analysis was 57% (+/- 10%), compared to a 79% (+/- 3%) DFS for
      the group with a normal pattern. By the log rank test, this difference was highly
      significant, p < or = 0.01. The relative risk of recurrence for the group with an
      abnormal SSCP pattern was 2.2. In a multivariate analysis including ER, PgR,
      ploidy, S-phase, age, and tumor size, an abnormal p53 by SSCP analysis and
      patient age were the only factors that independently predicted DFS at 5 years.
      CONCLUSION: Women with node-negative breast cancer who have tumors with
      alterations in the p53 gene, as indicated by SSCP analysis, have a significantly
      poorer prognosis and a higher rate of relapse at 5 years. The prognostic
      significance is maintained in a multivariate analysis including many established
      prognostic factors.

PMID- 8251648
TI  - Measurement of steroid hormone receptors in breast cancer patients on tamoxifen.
AB  - Estrogen (ER) and progesterone receptor (PgR) positive breast tumors often
      respond to tamoxifen, but ultimately progress as they become tamoxifen resistant.
      An accurate assessment of receptor status in specimens from tamoxifen-resistant
      patients could help to understand potential mechanisms of resistance and to
      predict response to second line hormonal therapies. However, since tamoxifen
      itself can affect ER and PgR determinations, assay results can be misleading. We
      measured ER and PgR by both ligand binding (LBA) and immunohistochemical (IHC)
      assays in 34 tumors from patients on tamoxifen, 30 of whom were displaying
      resistance to the drug. These tumors were classified into several receptor
      phenotypes. Eleven patients, 8 of whom were clearly progressing, expressed both
      receptors while on tamoxifen. ER was significantly less often negative when
      measured by IHC, suggesting that ER status by LBA was falsely negative in this
      group due to receptor occupancy by tamoxifen. Six patients had no detectable ER
      by LBA or IHC but still expressed PgR. The presence of PgR suggests that ER could
      still be functional, though undetectable, in these tumors, or that PgR is
      constitutively expressed by them. Finally, 12 patients were ER and PgR-negative
      by both assays, suggesting hormonal independence as the mechanism for resistance
      in this group. In a subset of patients with receptor assays both prior to
      tamoxifen and at the time of progression while taking the drug, we found that
      most ER-positive tumors converted to an apparent ER-negative status when assayed
      by LBA, while PgR status frequently remained unchanged. The continued expression
      of ER and/or PgR in many patients with tumor progression on tamoxifen indicates
      that mechanisms for resistance other than receptor loss are common in breast
      cancer.

PMID- 8251649
TI  - Tissue platelet derived-growth factor (PDGF) predicts for shortened survival and
      treatment failure in advanced breast cancer.
AB  - In a study of plasma and tissue platelet derived growth factor (PDGF)
      concentration in patients with breast cancer, elevated levels of plasma PDGF were
      found in a significant proportion, 11/37 (30%), of patients. Sixteen patients
      (43%) had tumors which expressed PDGF-AA and 6 patients had tumors which in
      addition expressed the BB isoform of PDGF. All patients with elevated plasma
      levels of platelet derived growth factor had tumors which expressed the growth
      factor on immunohistochemical staining of tumor cells. Furthermore there was a
      significant correlation between plasma levels of platelet derived growth factor
      and the intensity of tissue staining. Patients with stage four breast cancer with
      tumors which were positive for platelet derived growth factor had a significantly
      lower response rate to chemotherapy as well as significantly shorter duration of
      survival. In addition, patients with stage four breast cancer who had elevated
      plasma PDGF levels had a significantly shorter survival. These results indicate
      that elevated plasma levels of platelet derived growth factor in patients with
      breast cancer are derived from the tumor cells and suggest that platelet derived
      growth factor may play a significant role in control tumor cell growth.

PMID- 8251650
TI  - Controlled release low dose medroxyprogesterone acetate (MPA) inhibits the
      development of mammary tumors induced by dimethyl-benz(a) anthracene in the rat.
AB  - Medroxyprogesterone acetate (MPA) is well recognized to have beneficial effects
      for the treatment of advanced breast cancer which are comparable to those
      achieved with other forms of endocrine therapy. Using mammary tumors induced in
      the rat by dimethylbenz(a)anthracene (DMBA) as a model, we have studied the
      possibility that low dose MPA could prevent the development of these tumors.
      Single subcutaneous injection of Depo-Provera (crystalline suspension of MPA) or
      MPA encapsulated in biodegradable microspheres of 50:50 poly[DL-lactide-co
      glycolide] was given 7 days before oral DMBA. While 63% of intact animals
      developed palpable mammary tumors within 85 days after DMBA administration, tumor
      incidence decreased to 28% and 23% in animals who had received 30 mg and 100 mg
      of Depo-Provera, respectively. The same amounts of MPA delivered in microspheres
      caused a further decrease in tumor incidence to respective values of 7% and 6%.
      Average tumor area, on the other hand, decreased from 4.89 cm2 in intact rats to
      about 0.75 (0.57-0.88) cm2 and approximately 0.20 (0.14-0.22) cm2 in the Depo
      Provera and microsphere-treated groups, respectively. Using the 50:50 formulation
      of poly[DL-lactide-co-glycolide] designed to release MPA at a constant rate for a
      4-month period, the serum MPA concentration at 3 months was measured at 4.99 +/-
      0.43 ng/ml. Such data suggest that administration of a low dose controlled
      release formulation of MPA in 50:50 poly[DL-lactide-co-glycolide] microspheres
      could well be an efficient and well tolerated approach for the prevention of
      breast cancer in women.

PMID- 8251651
TI  - Expression of mdr1 gene in human breast primary tumors and metastases.
AB  - Expression of mdr1 gene has been evaluated in 34 tumor samples obtained from
      breast cancer patients who were classified according to their treatment, and
      clinical follow-up. No gene amplification was found. mdr1-RNA was never detected
      in 29 primary breast tumors including 5 samples from patients previously treated
      by 6 courses of 5-fluorouracil, epirubicin, cyclophosphamide (FEC). On the other
      hand, mdr1-RNA expression was detected in 1 local recurrence and 2 out of 3
      metastases, all of them being treated and exhibiting a poor evolution. A second,
      untreated local recurrence remained negative. Clinical follow-up for 7 to 48
      months in patients receiving chemotherapy showed that absence of mdr1-RNA could
      not be an accurate factor of satisfactory response to chemotherapy. But, all the
      patients with detectable mdr1-RNA exhibited a poor evolution and response to
      treatment. In conclusion, evaluation of mdr1-RNA seemed to be of little interest
      in primary breast tumors. However, the concomitant presence of an mdr1-RNA and a
      metastatic phenotype could give a new insight into the relationship between
      invasive and resistance properties of cancer cells. Such situations would need to
      be analyzed very carefully for a better utilization of chemotherapy.

PMID- 8251652
TI  - Paracrine interaction in co-culture of hormone-dependent and independent breast
      cancer cells.
AB  - A permeable solid support (Transwell Coll.) was used to develop serum-free co
      cultures allowing paracrine interactions between hormone-dependent (MCF-7,
      ZR75.1) and hormone-independent (MDAMB-231, BT20) breast cancer cell lines. Both
      hormone-independent cell lines were able to stimulate the growth of the hormone
      dependent lines, whereas the opposite was observed only in the case of BT20 co
      culture with ZR75.1 cells. The cell growth stimulation observed in co-cultures
      could be abolished by the addition to the culture medium of an excess of
      transforming growth factor alpha (TGF alpha) or insulin-like growth factor I (IGF
      I). Similarly, treatment with a neutralizing anti TGF alpha antibody impaired the
      growth stimulation exerted by hormone-independent cells on hormone-dependent
      cells. These results confirm the important role of paracrine interactions in
      control of the growth of human heterogeneous breast tumors and suggest that the
      main growth factors involved in such interactions are TGF alpha and probably some
      growth factors from the insulin-like growth factor family rather than IGF-I
      itself.

PMID- 8251653
TI  - Protein tyrosine kinase activity as a prognostic parameter in breast cancer, a
      pilot study.
AB  - Protein tyrosine kinase (PTK) activity was assayed in cytosolic extracts from
      normal breast tissue, benign tumors, and 84 T1-T2, N0-N1 M0, breast carcinomas.
      Normal breast tissue extracts yielded an average value of 1.9 +/- 1.1 pmol 32P
      incorporated/min/mg protein, whereas a mean of 12.5 +/- 6.1 was obtained for
      cancer samples. With a median follow-up of 34 months, in the series of 40
      patients classified N-, PTK positive patients presented a significantly smaller 3
      year disease free survival than the PTK negative ones. Multivariate analysis
      shows that PTK activity emerges as a potential prognostic factor in breast cancer
      (p = 0.02). These preliminary results will be updated on a bigger cohort of
      patients.

PMID- 8251654
TI  - Epidermal growth factor receptor levels increase but epidermal growth factor
      receptor ligand levels decrease in mouse mammary tumors during progression from
      hormone dependence to hormone independence.
AB  - Twenty-six serially transplanted Grunder (GR) strain mouse mammary tumors were
      analyzed for epidermal growth factor receptor (EGFR) and EGFR-ligand levels, in
      addition to steroid hormone receptors (estrogen receptor, ER, progesterone
      receptor, PgR). In concordance with earlier studies, hormone dependent (HD) and
      hormone responsive (HR) tumors were found to be positive for both ER and PgR,
      whereas hormone independent (HI) tumors contained only 30% of the ER
      concentration that was found in the HD tumors. PgR was undetectable in HI tumors.
      HI tumors contained 2.5 to 3-fold higher EGFR levels than HD/HR tumors, an
      observation which shows remarkable concordance with studies on EGFR in human
      breast cancer. On the other hand, the level of EGFR-ligand(s) was positively
      associated with ER levels and was three-fold higher in HD/HR tumors than in HI
      tumors. The low EGFR in HD/HR tumors relative to HI tumors may be the result of
      downregulation by EGFR ligands produced under ER control. During progression to
      hormone independence this downregulation of EGFR is then abolished in absence of
      ER. The increase in EGFR may therefore be a secondary effect rather than a key
      event in the progression to hormone independence in this mouse mammary tumor
      model.

PMID- 8251655
TI  - Malassezia furfur fungemia: a case report.
AB  - A laboratory-confirmed case of Malassezia furfur fungemia in a 71-year-old
      chronic total parenteral nutrition patient is described. The patient had
      extensive bowel necrosis secondary to vascular necrosis, and the infection
      appeared to be related to the use of Hickman catheter. A brief review of the
      literature about catheter-related malassezia sepsis, as well as salient aspects
      of laboratory diagnosis and identification of the fungus, are presented.

PMID- 8251656
TI  - Could you please comment regarding the use of iodine alcohol, 70% isopropyl
      alcohol and tincture of chlorohexidine in cleaning of silicone central venous
      catheter insertion sites and hubs.

PMID- 8251657
TI  - Laparoscopic Nissen fundoplication.
AB  - A technique for laparoscopic Nissen fundoplication is described and a series of
      11 cases is presented. The technique secures the patient to the operating table
      with three safety straps and the patient is then placed in a reverse
      Trendelenburg position with the hips flexed. The surgeon operates from the
      patient's right side using two midline trocar sites as the main operating ports.
      Other ports provide retraction and laparoscope access. The liver retractor is
      held by a mechanical arm. Once the esophageal peritoneum has been opened, the
      esophagus and diaphragmatic crura are dissected out and elevated by a Penrose
      drain sling. The short gastrics are divided and the fundus is brought posterior
      to the esophagus passing from left to right. A large Maloney dilator is placed in
      the esophagus and the fundal wrap is sutured to the anterior aspect of the
      stomach by three sutures; the inferior--most of which incorporates the anterior
      wall of the esophagus. Once the fundoplication is completed, the dilator is
      replaced by a nasogastric tube. Postoperatively, patients are given clear liquids
      and when these are tolerated the nasogastric tube is removed. Most patients are
      discharged on the second or third postoperative day. Operating time averaged 147
      min, and all patients returned to unrestricted activity within 2 to 3 weeks. All
      patients reported complete relief of gastroesophageal reflux. Average follow up
      was 120 days with a median of 148 days. Long-term follow up is in progress.

PMID- 8251658
TI  - Laparoscopically assisted subtotal colectomy.
AB  - A technique for laparoscopic total resection of the colon performed in six
      patients is reported. The diseased colon was separated from the mesocolon and the
      greater omentum by electrocoagulation and sharp dissection. The mesenteric
      vessels were divided using an Endo GIA stapling device (AutoSuture, France). The
      whole colon was removed after transection of the rectum and extraction through a
      right minilaparotomy. A primary stapled end-to-side ileorectal anastomosis was
      performed through the anus under laparoscopic guidance. This technique can be
      applied to cases involving a variety of benign lesions of the entire bowel or
      multifocal small malignant colonic neoplasms with a decrease in patient morbidity
      and shorter inpatient period.

PMID- 8251659
TI  - Laparoscopic adrenalectomy for primary aldosteronism: a new operative method.
AB  - From January 17, 1992 to January 16, 1993, laparoscopic adrenalectomy was
      performed in 7 patients (3 men, 4 women) with primary aldosteronism ranging in
      age from 35 to 65 years (mean 48.7 years). Five of the adrenal lesions were on
      the left side and two were on the right. Five to six trocar-sheath units were
      used, and adrenal tumors were successfully removed with adjacent normal adrenal
      glands in all patients. The operative time ranged from 165 to 572 min (mean 302
      min), operative blood loss was between 50 and 450 ml (mean 217.2 ml), and there
      was no major complication. In conclusion, laparoscopic adrenalectomy is a safe
      alternative operative method for primary aldosteronism, although application of
      this technique to other types of adrenal lesions remains to be examined.

PMID- 8251660
TI  - Myoelectric motility patterns following open versus laparoscopic cholecystectomy.
AB  - Laparoscopic surgery is associated with a lack of postoperative ileus. To
      determine if differences exist in postoperative motility patterns, 8 dogs were
      instrumented with bipolar electrodes 10-14 days prior to open (n = 4) or
      laparoscopic (n = 4) cholecystectomy. In both groups, Phase II activity
      disappeared in the first 24 h after operation. The appearance of the migrating
      myoelectric complex in the small intestine and the migrating colonic complex were
      used as criteria for recovery from postoperative ileus. Postoperative migrating
      myoelectric complex cycle length, migrating myoelectric complex, migration
      velocity, and colonic spike bursts/hour were also measured. No statistically
      significant differences were observed between groups in study parameters
      examined. Postoperative myoelectric motility patterns in dogs undergoing open
      versus laparoscopic cholecystectomy are not different. Other factors may be
      responsible for the rapid return to oral intake following laparoscopic
      cholecystectomy.

PMID- 8251661
TI  - Advantages of laparoscopic cholecystectomy in the elderly and in patients with
      high ASA classifications.
AB  - Two hundred and thirty-three patients underwent cholecystectomy at Mercy Hospital
      of Pittsburgh during the popularization of laparoscopic cholecystectomy.
      Laparoscopic cholecystectomy was performed in 167 of these patients while the
      remaining 66 patients had an open cholecystectomy. A statistically significant
      increase in the incidence of morbidity was observed with advancing age (p <
      0.001, odds ratio 2.33) as well as in patients with higher ASA classes (p <
      0.001, odds ratio 2.31). Overall, laparoscopic cholecystectomy was associated
      with a markedly lower incidence of morbidity than the open procedure (7% versus
      47%, p < 0.001). A multiple logistic regression model was applied to the study
      population due to the fact that those patients who underwent open cholecystectomy
      tended to be older individuals with more clinically significant associated
      medical conditions than those individuals who underwent the laparoscopic
      procedure. When the logistic regression model was applied to control for the
      differences in age, associated illnesses, and ASA class between the two groups; a
      seven fold increase in the risk of morbidity was found in the open group as
      compared to the laparoscopic group (p < 0.001, odds ratio 7.31). These findings
      favor the use of laparoscopic cholecystectomy over open cholecystectomy in all
      eligible patients, especially elderly patients and those patients in higher ASA
      classes.

PMID- 8251662
TI  - Digitally assisted laparoscopic drainage of multiple intraabdominal abscesses.
AB  - Laparoscopic drainage of multiple walled off intraabdominal abscesses may be
      difficult to perform safely due to a lack of tactile sensation. A single finger
      introduced through a small abdominal incision can be used to aid in the
      dissection and may obviate the need for open laparotomy in some cases. Digitally
      assisted laparoscopic exploration and dissection utilizes the superior
      visualization of laparoscopy without completely sacrificing the benefits of
      tactile sensation. A case is reported in which this technique was successfully
      employed to drain multiple intraabdominal abscesses in a young boy.

PMID- 8251663
TI  - A simplified method of retrieving gallstones from the abdominal cavity following
      laparoscopic transcystic common duct stone extraction.
AB  - Laparoscopic techniques for common bile duct stone extraction are becoming
      increasingly more refined. Current options for removal of gallstones from the
      common bile duct include: (1) transcystic choledochoscopic stone extraction, (2)
      combined laparoscopic/fluoroscopic stone extraction using a helical stone basket,
      and (3) laparoscopic choledochotomy with T-tube insertion. The tactics for
      subsequent removal of the stones from the abdominal cavity to the outside have
      not yet received as much attention. A technique is reported for stone recovery
      which has been found to be useful following transcystic choledochoscopy.

PMID- 8251664
TI  - A safe simple method for removal of the gallbladder through the umbilical trocar
      site during laparoscopic cholecystectomy.
AB  - After laparoscopic resection, the gallbladder must be removed, usually through
      the umbilical trocar site. Occasionally, there is difficulty in removing the
      gallbladder from the abdominal cavity due to its large dimensions or its
      contents. There are two main options to extract the gallbladder in such cases.
      One is evacuation of its content through the gallbladder neck protruding from the
      abdominal wall. The second is extension of the periumbilical fascial opening. In
      the first method, gallbladder content might sometimes spill into the peritoneal
      cavity or contaminate the incision site. In the second, there might not be enough
      control concerning the extent of injury caused to the periumbilical abdominal
      wall during enlargement of the fascial opening. A simple precise and safe method
      is suggested to enlarge the fascial incision by direct vision using
      transillumination.

PMID- 8251665
TI  - A new endoscopic drainage technique for pancreatic abscesses.
AB  - Acute pancreatitis sometimes leads to pancreatic abscess with a high mortality
      rate when appropriate drainage is not applied. Pancreatic pseudocysts are also
      major complications of pancreatitis, which usually need to be treated only when
      they are symptomatic; they sometimes lead to disseminated intravascular
      coagulopathy or intraabdominal bleeding if they maturate. Conventional pancreatic
      drainage operations have sometimes been so invasive that they cannot be applied
      for severe cases with renal failure and disseminated intravascular coagulopathy.
      To avoid the risks of conventional drainage operations for pancreatic abscesses,
      a low invasive and effective percutaneous drainage technique guided by a
      laparoscope was developed and employed to a high-risk patient with post
      pancreatitic pancreatic abscess. After the operation, leukocytosis and high fever
      improved dramatically. One year after discharge from the hospital, no recurrence
      of abscesses or leukocytosis have been found. Thus, this technique should be
      considered as a first option for the pancreatic drainage operation.

PMID- 8251666
TI  - Laparoscopic staging of Hodgkin's lymphoma.
AB  - A 57-year-old female with Hodgkin's lymphoma, diagnosed by a cervical lymph node
      biopsy and surgically staged laparoscopically, is presented. Staging included a
      pelvic and para-aortic lymphadenectomy as well as splenectomy. Laparoscopic
      staging of Hodgkin's lymphoma has not been previously reported. The procedure,
      its limitations, and potential modifications are discussed.

PMID- 8251667
TI  - Pancreatic cystogastrostomy by combined upper endoscopy and percutaneous
      transgastric instrumentation.
AB  - Minimally invasive endoscopic and radiologic techniques have been reported for
      internal gastric drainage of pancreatic pseudocysts but these have significant
      technical limitations. A purely endoscopic approach to cystogastrostomy provides
      limited access for instrumentation and hemostasis. Radiologically-guided
      percutaneous techniques cannot regularly provide an adequately wide
      cystogastrostomy opening. Reported is a patient who had a pancreatic
      cystogastrostomy performed using a minimally invasive surgical approach combining
      upper endoscopy and percutaneous transgastric surgical instrumentation. The upper
      endoscope essentially served as a camera. A percutaneous endoscopic gastrostomy
      tube served as a port for inserting laparoscopic instruments into the stomach.
      The laparoscopic instruments were used to create a 1.5 cm cystogastrostomy
      opening similar in size to what could be created by an open abdominal approach.
      The laparoscopy instruments provided good tactile feedback and excellent
      hemostatic control. Avoiding an open abdominal procedure shortened postoperative
      recovery and reduced patient discomfort. Although the pseudocyst recurred once,
      the same procedure was performed again and there has not been a recurrence for 10
      months. The authors conclude that this minimally invasive surgical procedure
      provides an excellent alternative approach for internal drainage of selected
      pancreatic pseudocysts.

PMID- 8251668
TI  - Extraperitoneal endoscopic vesicourethral suspension.
AB  - A new operative technique of vesicourethral suspension utilizing an entirely
      extraperitoneal endoscopic approach is described. This method offers a minimally
      invasive alternative to other operative procedures, including the transperitoneal
      laparoscopic approach, for the treatment of stress urinary incontinence.

PMID- 8251669
TI  - Abdominal wall sinus tract secondary to gallstones: a complication of
      laparoscopic cholecystectomy.
AB  - A persistent sinus tract of the abdominal wall caused by retained fragments of
      gallstones following laparoscopic cholecystectomy is reported. Review of the
      literature and suggested technique and methods to avoid this complication are
      described.

PMID- 8251670
TI  - An unusual case of a retained stone following laparoscopic cholecystectomy.
AB  - A patient with gallstone pancreatitis was managed by endoscopic sphincterotomy
      followed by a laparoscopic cholecystectomy. At the time of surgery, an
      intraoperative cholangiogram disclosed the presence of a residual calculus, which
      was erroneously thought to be in the common bile duct. A repeat ERCP showed that
      the stone was, in fact, in a long cystic duct stump which was fortunately
      accessible to endoscopic extraction.

PMID- 8251671
TI  - Laparoscopic cholecystectomy in childhood.

PMID- 8251672
TI  - Physicians make a difference.

PMID- 8251673
TI  - A loathsome custom.

PMID- 8251674
TI  - Working in harmony with how people quit smoking naturally.

PMID- 8251675
TI  - Identifying and assisting smokers who have difficulty quitting on their own.

PMID- 8251676
TI  - Tobacco use control in Rhode Island: the project ASSIST blueprint for the 1990s.

PMID- 8251677
TI  - Smoking control at the workplace: current status and emerging issues.

PMID- 8251678
TI  - The role of primary care physicians in smoking cessation.

PMID- 8251679
TI  - Cigarette smoking-attributable mortality, Rhode Island, 1989.

PMID- 8251680
TI  - Images and patterns in medicine: sigmoid volvulus.

PMID- 8251681
TI  - Patient counseling in community pharmacy and its relationship with prescription
      payment methods and practice settings.
AB  - OBJECTIVE: To determine whether patient counseling activities in community
      pharmacies are related to payment method and practice setting. DESIGN: Randomly
      selected pharmacists voluntarily performed self-data collection (39 percent
      participation rate) of counseling activities for 40 hours. Observational data
      were also collected by trained observers. SETTING: Community pharmacies. RESULTS:
      Forty-seven pharmacists in national chain pharmacies and 26 in independent
      pharmacies collected data on 3766 counseling events. Patient counseling rates,
      defined as percentage of patients counseled per prescription per pharmacist, were
      significantly higher (p < 0.05) for self-pay (median 12.9 percent) and Medicaid
      (median 13.0 percent) than for capitation patients (median 7.9 percent). Rates
      were somewhat higher (p = 0.06) for chain (median 17.7 percent) than for
      independent pharmacists (10.7 percent). Although there was no difference in terms
      of pharmacist-initiated counseling, chain pharmacists had higher rates of patient
      initiated counseling per prescription (median 4.3 percent) than independent
      pharmacists (median 2.7 percent) (p < 0.01). Counseling information was related
      to payment method and practice setting. A significantly higher percentage (p <
      0.01) of counseling events for capitation patients pertained to chronic therapies
      (33.6 percent) compared with counseling events involving patients using other
      payment methods (21.8-24.8 percent). A strong correlation between observational
      data and self-reported data was found (Pearson r = 0.696, p < 0.001).
      CONCLUSIONS: The finding that pharmacists counsel capitation patients less
      frequently may be attributable to financial incentives or to pharmacists'
      perception that these patients do not need to be counseled. Independent
      pharmacists' higher number of capitation patients and increased workloads may
      have affected their counseling activities. These findings have implications for
      pharmacy service reimbursement programs, practice conditions, and continuing
      education programs.

PMID- 8251682
TI  - Potential interaction between carbamazepine and loxapine: case report and
      retrospective review.
AB  - OBJECTIVE: To report a potential interaction between carbamazepine (CBZ), an
      anticonvulsant medication, and loxapine, an antipsychotic. CBZ is being
      increasingly used to treat a variety of psychiatric disorders. Because of this,
      the potential for multiple-drug therapy and subsequent drug interactions is
      increased. METHODS: We prospectively monitored plasma CBZ and carbamazepine
      epoxide (CBZE) concentrations in a single patient during and after withdrawal of
      loxapine comedication. Additionally, we retrospectively evaluated four patients
      who had received concomitant therapy with CBZ and loxapine. RESULTS: Plasma
      CBZE/CBZ ratios decreased from 0.76 to 0.18 following discontinuation of
      loxapine. Absolute CBZE plasma concentrations also decreased from 1.7 to 0.6
      micrograms/mL after loxapine therapy was stopped. Retrospectively screened
      patients who were receiving concomitant loxapine-CBZ therapy all had unusually
      elevated CBZE/CBZ plasma concentration ratios (0.75-1.91). CONCLUSIONS: These
      cases suggest that an interaction occurs between loxapine and CBZ. Possible
      mechanisms include either induction of CBZ metabolism to its epoxide metabolite,
      or inhibition of the enzymatic metabolism of CBZE (epoxide hydrolase).

PMID- 8251683
TI  - Phenformin-induced lactic acidosis: a forgotten adverse drug reaction.
AB  - OBJECTIVE: To document a case of severe metabolic and lactic acidosis secondary
      to phenformin. This adverse effect has almost been forgotten as 15 years have
      passed since its withdrawal from the US market. CASE SUMMARY: A 64-year-old man
      presented with a four-day history of left upper abdominal pain and a one-week
      history of constipation and diarrhea. His arterial blood gases were pH 6.7, pCO2
      2.80 kPa, and pO2 12.00 kPa with 90% oxygen saturation on room air. Serum
      chemistries indicated an unmeasurable serum bicarbonate concentration, anion gap
      52 mmol/L, lactate concentration 29.5 mmol/L, blood urea nitrogen 6.63 mmol/L,
      creatinine 229.84 mumol/L, and blood glucose 4.35 mmol/L. There were low levels
      of urine and serum ketones. In the emergency department, he required
      resuscitation for hypotension and bradycardia. His diagnosis was lactic and
      ketoacidosis secondary to phenformin. The patient was treated with NaCl 0.9%,
      sodium bicarbonate, insulin, and hemodialysis. Although he survived the initial
      insult of lactic and ketoacidosis, his hospital course was complicated and he
      died on hospital day 105. CONCLUSIONS: Treatment of lactic acidosis is difficult
      and challenging. The continued availability of phenformin in neighboring
      countries, and the renewed interest in biguanide therapy for treating diabetes
      mellitus make it an important diagnosis of exclusion in diabetic patients who
      present with severe acidosis. Metformin, another biguanide under investigation
      for the treatment of diabetes mellitus, is associated with a much lower incidence
      of lactic acidosis than is phenformin.

PMID- 8251684
TI  - Inadvertent intravenous administration of an elemental enteral nutrition formula.
AB  - OBJECTIVE: To report a case of intravenous infusion of an elemental enteral
      nutrition formula. CASE SUMMARY: A 65-year-old woman with a high-output
      jejunostomy required fluid and electrolyte replacement via a central line and
      enteral nutrition support via a gastrostomy tube. She inadvertently received 160
      mL of half-strength elemental enteral nutrition formula (Vivonex TEN) via her
      central venous catheter. After four hours of the infusion, the patient felt ill
      and was found to by hypotensive and pyrexic. Over the next 24 hours she developed
      severe back pain and diffuse muscle tenderness. Her creatine kinase concentration
      was mildly elevated and there were no electrocardiographic changes. There was no
      rise in serum amylase concentration. Her renal function deteriorated markedly
      over the following three hours but responded to hydration and diuretic therapy.
      Liver enzymes, slightly elevated prior to this event, remained unchanged. Blood
      cultures were negative, but prophylactic therapy with vancomycin and ceftazidime
      was instituted. The patient recovered and was discharged eight days later.
      DISCUSSION: Previous reports of inadvertent intravenous administration of enteral
      feedings have described such complications as osmolarity, microembolism,
      hypersensitivity, and septicemia. This patient's nonfatal outcome may have been
      related to the infusion of the enteral formula via the central rather than the
      peripheral route, the infusion of an elemental rather than a whole protein
      formula, and the use of sterile water to reconstitute the formula. CONCLUSIONS:
      Particular care should be taken when a patient has more than one catheter
      implanted on the chest or abdomen (e.g., central venous or peritoneal dialysis
      catheter). It is important that inservice training is provided and written
      protocols are available for the safe infusion of enteral formulas.

PMID- 8251685
TI  - Endstage liver disease associated with nitrofurantoin requiring liver
      transplantation.
AB  - OBJECTIVE: To report the apparent development of endstage liver disease secondary
      to nitrofurantoin administration. PATIENT: A 40-year-old woman developed hepatic
      failure after receiving nitrofurantoin 200 mg po bid for one month for
      prophylaxis against urinary-tract infections. Symptoms first occurred after two
      weeks of nitrofurantoin therapy. Other causes of hepatic failure (e.g., viral
      infection, autoimmune disorder, concomitant medications, cancer, Wilson's
      disease, ethanol abuse, pregnancy) were ruled out. CONCLUSIONS: Acute and chronic
      hepatic injury has previously been reported with the use of nitrofurantoin. The
      proposed mechanism may be immunoallergic or metabolic in origin. On evaluating
      concomitant diseases and medications in our patient as well as the temporal
      sequence of her signs and symptoms, it appears that she developed hepatic failure
      secondary to the use of nitrofurantoin, ultimately necessitating orthotopic liver
      transplantation. The potential for the development of such a severe adverse
      reaction warrants careful evaluation of symptoms that may potentially be caused
      by hepatic damage as well as immediate discontinuation of nitrofurantoin in
      patients presenting with jaundice.

PMID- 8251686
TI  - Pharmacodynamic interpretation of adrenocorticotropin stimulation tests.
AB  - OBJECTIVE: To report a pharmacodynamic model that describes increases in cortisol
      concentrations during administration of an adrenocorticotropin (ACTH) infusion,
      taking into account both steroid secretion and elimination. DATA SOURCES:
      Previously published data. DATA SYNTHESIS: Using a population estimate of the
      elimination rate constant for cortisol and equations describing changes in
      cortisol concentration versus time, a value for the rate of cortisol secretion
      (Rcort) was derived. The Rcort value more directly represents the capacity for
      adrenal secretion of cortisol. CONCLUSIONS: Pharmacodynamic modeling techniques
      were used to successfully describe the rate of cortisol secretion during an ACTH
      infusion. This model can be applied to assess the extent of adrenal suppression
      after long-term corticosteroid therapy or in the presence of disease states.

PMID- 8251687
TI  - Stability of spironolactone in an extemporaneously prepared suspension at two
      temperatures.
AB  - OBJECTIVE: To determine the stability of spironolactone in an extemporaneously
      prepared suspension at 22 and 4 degrees C over a three-month storage period.
      DESIGN: Spironolactone suspension (1 mg/mL) was prepared in syrup NF,
      carboxymethylcellulose, and purified water USP. The suspension was stored in ten
      amber glass prescription bottles; five were stored at 22 degrees C and five at 4
      degrees C. Samples were drawn from each bottle and analyzed in duplicate (n = 10)
      on days 0, 7, 14, 28, 42, 56, 70, and 91. Spironolactone concentrations were
      measured by a reproducible and stability-indicating HPLC method. Inspection of
      visual and pH changes also was performed on each study day. RESULTS: The mean
      concentration of spironolactone was always higher than 98 percent of its initial
      concentration. The pH and appearance of the suspension did not change
      substantially. CONCLUSIONS: Spironolactone was stable in a suspension containing
      syrup, carboxymethylcellulose, and purified water for three months during storage
      in amber glass bottles at both 22 and 4 degrees C.

PMID- 8251688
TI  - Treatment of postmenopausal osteoporosis with etidronate.

PMID- 8251689
TI  - Treatment of wounds with procuren.

PMID- 8251690
TI  - Topical nitrate treatment of impotence.

PMID- 8251691
TI  - Treatment of aspergillosis with itraconazole.
AB  - OBJECTIVE: To review the role of itraconazole as oral therapy for the major
      infections caused by Aspergillus spp.: allergic bronchopulmonary aspergillosis,
      aspergilloma, and invasive aspergillosis. DATA SOURCES: A MEDLINE search of
      articles published in the English language between 1986 and 1993 was used to
      identify relevant citations, including review articles. In addition, a search of
      the published abstracts of the past two Interscience Conferences on Antimicrobial
      Agents and Chemotherapy (ICAAC) was performed. STUDY SELECTION: Clinical trials
      that evaluated itraconazole therapy in either allergic bronchopulmonary
      aspergillosis, aspergilloma, or invasive aspergillosis were critically reviewed.
      Trials were evaluated based upon entry criteria for the diagnosis of each type of
      aspergillosis, risk factors for the development of aspergillosis (neutropenia,
      transplant recipient, hematologic malignancy), prior antifungal chemotherapy, and
      dose and duration of itraconazole therapy. DATA SYNTHESIS: Overall, the clinical
      trials of itraconazole therapy for aspergillosis are limited and of variable
      quality. In the treatment of allergic bronchopulmonary aspergillosis,
      itraconazole has been reported to prompt a reduction in corticosteroid dosage in
      selected patients. There have been no controlled trials of itraconazole as
      treatment for aspergilloma, but data from several open-label trials suggest that
      this agent may be of clinical benefit in aspergilloma, primarily as an
      alternative to surgery. The use of itraconazole for invasive aspergillosis has
      been evaluated in several trials, most often in patients who were intolerant to
      amphotericin B treatment. Response to oral itraconazole has generally been
      promising. CONCLUSIONS: Although itraconazole offers promise for oral therapy
      against infections caused by Aspergillus spp., it should not presently be
      regarded as primary therapy for any of these diseases. Amphotericin B, in doses
      ranging from 1 to 1.5 mg/kg to a total dose of 1.5-4.0 g, should remain the
      treatment of choice in both aspergilloma and invasive aspergillosis. Itraconazole
      use should be restricted to patients who experience severe toxicity with
      amphotericin B therapy. Corticosteroids continue to be first-line therapy for
      allergic bronchopulmonary aspergillosis, with the use of itraconazole reserved
      for those patients who would benefit from a reduction in corticosteroid dose.

PMID- 8251692
TI  - Paroxetine: a selective serotonin reuptake inhibiting antidepressant.
AB  - OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical investigations,
      adverse effects, and dosing strategies of paroxetine as a treatment of major
      depression. DATA SOURCES: Specific paroxetine information was selected from a
      MEDLINE search using paroxetine as the search term. Other sources included manual
      searches of pertinent journal article references, meeting abstracts, and the
      manufacturer. STUDY SELECTION: Clinical investigations with a blind, controlled
      (placebo and/or active), randomized design were selected. With the exception of
      treatment-resistant depression, no short-term, open investigations were selected.
      DATA EXTRACTION: Clinical investigations were evaluated for design, sample size,
      diagnosis, duration, definition of response, and outcome. Data from all
      investigations were selected by one author and reviewed by both authors. DATA
      SYNTHESIS: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) recently
      approved for the treatment of major depression. It is a potent and selective
      inhibitor of serotonin reuptake and has weak or no activity on the other
      monoamines; it is also weakly anticholinergic. Although pharmacokinetic
      parameters are variable, paroxetine is generally well absorbed, highly protein
      bound, hepatically cleared, and has no active metabolites. Clinical
      investigations support paroxetine's effectiveness as an antidepressant in an
      outpatient population with moderately severe depression. Its effectiveness is
      superior to that of placebo and is comparable to that of active controls. The
      majority of investigations have been six weeks in duration. Additional data are
      required to support paroxetine's promise for longer treatment periods (i.e., > or
      = 1 y), in the elderly, and for treatment-resistant depression. Adverse effects
      appear to be similar to those caused by the other SSRIs; some of the most common
      are nausea, diarrhea, insomnia, dry mouth, and nervousness. Significant drug
      interactions may occur with the monoamine oxidase inhibitors, phenobarbital, and
      phenytoin. CONCLUSIONS: Paroxetine is safe and effective for treatment of
      outpatients with moderately severe depression. Further clinical data and
      experience are necessary to determine this agent's place in the long-term
      treatment of major depression.

PMID- 8251693
TI  - Enoxaparin: the low-molecular-weight heparin for prevention of postoperative
      thromboembolic complications.
AB  - OBJECTIVE: To introduce readers to a new low-molecular-weight heparin (LMWH)
      product, enoxaparin. The chemistry, pharmacology, pharmacodynamics, clinical
      efficacy in thromboembolic prophylaxis following surgery, and adverse effects are
      reviewed. DATA SOURCES: A MEDLINE search of the English-language literature was
      used to identify relevant literature. STUDY SELECTION: A focus was placed on
      human clinical studies with well-accepted measures of antithrombotic efficacy
      endpoints, i.e., venography and ultrasonography. Emphasis was on pharmacologic
      and pharmacokinetic studies conducted in humans. DATA EXTRACTION: Most data were
      extracted from double-blind, controlled clinical studies. Other study designs
      were accepted if the results were believed to be significant. Pharmacology and
      pharmacokinetic data were selected from studies with exceptional design conducted
      in humans. DATA SYNTHESIS: Enoxaparin is a polysaccharide chain produced by the
      depolymerization of heparin. In comparison with heparin, which has an average
      molecular weight of 12,000-15,000 daltons, the average molecular weight of
      enoxaparin is approximately 4500 daltons. Enoxaparin does not form a complex with
      antithrombin III and thrombin as extensively as does heparin; however, the anti
      Xa activity of enoxaparin is similar. The significance of this fact is an
      enhancement of antithrombotic activity and clinical efficacy. Trials comparing
      enoxaparin with other thromboembolic prophylaxis techniques are ongoing.
      CONCLUSIONS: Thromboembolism remains one of the major complications of all
      surgical procedures. Attempts have been made throughout the last century to
      develop the most effective means to prevent this complication. Clinical studies
      performed throughout the world have shown that enoxaparin is superior or
      equivalent to other antithrombotic agents, including heparin, in preventing the
      formation of venous thromboembolism. In addition, enoxaparin appears to possess
      an equivalent or lower incidence of bleeding complications when compared with
      heparin prophylaxis. Enoxaparin is expected to be joined by other LMWH products
      in the future. As a result, the methods of providing effective prophylaxis
      against thromboembolic complications is expected to change in the coming years.

PMID- 8251694
TI  - Enterococcus, an emerging pathogen.
AB  - OBJECTIVE: To review the bacterial genus Enterococcus with respect to its
      epidemiology, specific infections in humans, mechanisms of resistance and
      tolerance, and antimicrobial treatment. DATA SOURCES: A MEDLINE search of English
      language journal articles published from 1977 to 1992 was completed. Articles
      published prior to 1977 were identified through Index Medicus and from references
      appearing in the bibliographies of other journal articles. Information also was
      acquired from abstracts, personal communication with infectious disease
      specialists with active research in the area of enterococcal infection, and
      conference proceedings. STUDY SELECTION: In vitro data; animal models of
      enterococcal infection; case reports; and case-controlled, cohort, and randomized
      controlled trials in humans were evaluated for relevant information. DATA
      EXTRACTION: Studies were evaluated by their methodologic strength (e.g.,
      randomized controlled trial), reporting of clinically relevant outcomes (e.g.,
      clinical response to antimicrobial therapy), statistical analyses, and
      accountability of all patients who entered the study. DATA SYNTHESIS: The
      incidence of enterococcal infections has increased in recent years and
      enterococci are now the second most frequently reported nosocomial pathogens.
      Enterococcus faecalis is the pathogen responsible for most enterococcal
      infections seen today; it has been implicated as an important cause of
      endocarditis, bacteremia, urinary tract infections, and intraabdominal
      infections. CONCLUSIONS: Enterococcal infection is of particular concern
      clinically because of its resistance to several antibiotics. Controlled
      comparative clinical trials of antimicrobial therapy in humans are lacking for
      several enterococcal infections. Therefore, the recommendations for antimicrobial
      therapy presented in this review are guidelines that reflect our current
      understanding of antibiotics used for enterococcal infection.

PMID- 8251695
TI  - Prophylaxis of HIV infection following occupational exposure.
AB  - OBJECTIVE: To review the risk of HIV infection following occupational exposure,
      the theoretical basis for chemoprophylaxis, investigative experience with
      chemoprophylaxis in animals and humans, and the economic aspects of postexposure
      chemoprophylaxis. DATA SOURCES: English-language articles and conference
      proceedings pertaining to the risk of occupational HIV infection and to
      postexposure chemoprophylaxis. STUDY SELECTION: Studies evaluating
      chemoprophylaxis of HIV infection following occupational exposure were selected
      for review. Abstracts reporting ongoing clinical trials were also included. DATA
      EXTRACTION: In vitro studies are discussed to provide the immunologic rationale
      for chemoprophylaxis. Animal studies examining the efficacy of chemoprophylaxis
      in preventing non-HIV retroviral infection are reviewed, and their applicability
      to human HIV infection is critically evaluated. Human studies and case reports
      describing attempts at chemoprophylaxis of HIV infection following occupational
      exposure are discussed. DATA SYNTHESIS: Chemoprophylaxis of HIV infection
      following occupational exposure has focused on the use of zidovudine (ZDV)
      because it was previously the only antiretroviral agent approved for treating HIV
      infection. Animal models of retroviral infection provide conflicting data
      regarding the efficacy of ZDV chemoprophylaxis, and there are important questions
      about the applicability of animal data to human HIV infection because of
      differences in natural histories of non-HIV retroviral infections, inoculum size,
      dosing of ZDV, and routes of infection. Human surveillance studies are thus far
      inadequate to determine the efficacy of ZDV prophylaxis because of the very low
      HIV seroconversion rates following occupational exposure. ZDV is well tolerated
      during short-term administration in people without HIV infection, but long-term
      safety is unknown. In addition, the true cost-benefit ratio of ZDV
      chemoprophylaxis is uncertain. CONCLUSIONS: Current data from in vitro, animal,
      and human studies are inadequate to define the appropriate role of ZDV in
      preventing HIV infection following occupational exposure. Limited toxicity data
      and the high cost of treatment must be weighed against the theoretical benefits
      of ZDV use in this setting. The decision to employ ZDV for postexposure
      prophylaxis must ultimately be based on existing institutional policies, the
      attitude of the responsible physician regarding such practice, and/or the desires
      of the exposed healthcare worker after being properly informed of potential risks
      and benefits.

PMID- 8251696
TI  - Pharmacoepidemiology of clozapine in 202 inpatients with schizophrenia.
AB  - OBJECTIVE: To evaluate clozapine in a field trial for hospitalized patients with
      treatment-resistant schizophrenia. METHOD: The setting consisted of a large,
      state-operated, public psychiatric system. The protocol called for the treating
      psychiatrist to provide symptom- and adverse-effect ratings at four times
      following the start of drug therapy. The outcome criteria included the Sandoz
      study outcome measure of symptom improvement as well as discharge status for one
      year of follow-up. To assess the validity of the ratings, several measures of
      internal consistency were determined. Clozapine therapy was started in 227
      patients, and symptom data are available for 202. RESULTS: Overall, 33 percent (n
      = 66) of the patients were improved at the end of one year of treatment; 12
      percent (n = 24) maintained symptom improvement at all three evaluation times.
      Modest, statistically significant improvement after 12 weeks compared with
      baseline Brief Psychiatric Rating Scale (BPRS) total scores was observed for the
      patients continuing medication (n = 152); the emergence of a previously
      unimproved group (n = 26) explains this modest improvement. However, in the
      analysis of all patients (n = 202), (including dropouts), there was no
      significant symptom improvement after 12 weeks. Lower baseline BPRS scores
      predicted significant symptom improvement after 12 weeks of treatment. Among
      those medicated for one year, the pattern of symptom improvement showed that the
      probability of late improvement was 0.26 for those previously unimproved, and the
      probability of a 12-week responder losing improvement was 0.23, resulting in a
      net group gain of 3 cases in 100. By the end of one year, 8 percent (n = 17) of
      the cohort was discharged, and 3 percent (n = 7) was transferred to another
      facility while continuing to receive clozapine. Of the 227 original patients
      started on clozapine therapy, medication was discontinued for adverse effects in
      11 percent (n = 25): white blood cell count (WBC) decrease (but no
      agranulocytosis) in 5 percent (n = 12), seizures in 1 percent (n = 3), one
      patient with seizures and decreased WBC count, and other events (e.g.,
      cardiovascular changes, fever, or possible neuroleptic malignant syndrome) in 4
      percent (n = 9). Patient refusal was reported for 6 percent (n = 13) of those
      starting treatment. CONCLUSIONS: Although only 19 percent of the patients
      exhibited improvement at 6 weeks, the response rate at 12 weeks (29 percent) for
      this naturalistic study cohort was similar to that in the major, double-blind,
      six-week, controlled, clinical trial of clozapine. The impersistence of response
      as symptoms were followed for up to one year is a finding that deserves rigorous
      evaluation.

PMID- 8251697
TI  - Low-molecular-weight heparins: do good things really come in small packages?

PMID- 8251698
TI  - Meaningful interpretation of risk reduction from clinical drug trials.
AB  - OBJECTIVE: To illustrate the concepts of relative and absolute risk reduction,
      and by example, present and discuss the results of prevention trials that have
      evaluated the impact of drug therapy on cardiovascular disease. Additional
      approaches to evaluating the results of prevention trials are also presented.
      DATA SOURCES: Data were gathered from eight frequently quoted major
      cardiovascular intervention trials. CONCLUSIONS: Reference to large reductions in
      relative risk in review papers, newspapers, and at professional meetings can lead
      to false expectations among clinicians and patients regarding the potential
      impact of the treatment in individual patients. When making decisions about
      preventive drug therapy, clinicians are encouraged to examine measures other than
      relative risk reduction and to include the patient in the decision process.
      Educators should emphasize these other measures of outcome and not rely solely on
      relative risk reduction in discussing particular areas of therapeutics.

PMID- 8251699
TI  - Pharmacy practice and education in the People's Republic of China.
AB  - OBJECTIVE: To describe the pharmacy profession and the education programs
      available to train pharmacists in the People's Republic of China (PRC). The
      practice of pharmacy in the hospital setting and the current development of
      clinical services are also described. BACKGROUND: There are two streams of
      medical practices in the PRC: traditional Chinese medicine and Western medicine.
      Hospital and community pharmacies are responsible for the dispensing of
      medicinals used for both streams of medical practices. Forty-two colleges of
      pharmacy offer pharmacy education, half of which provide a Western medicine
      approach and the other half traditional Chinese medicine. Both types of colleges
      offer a four-year curriculum with options for specialization. Opportunities for
      graduate study are also available. Most of the graduates work in hospital
      pharmacies. Hospital pharmacies participate in the bulk manufacture of drugs and
      parenteral fluids. A bulk dispensing system is used by some hospitals; individual
      patient doses are dispensed in others. Recently, the need to develop clinical
      pharmacy services in PRC was recognized and training courses were begun.
      Curricula with specialization in clinical pharmacy are being considered by
      colleges of pharmacy. CONCLUSIONS: It is anticipated that through increased
      awareness of the potential contribution of pharmacists in the PRC healthcare
      system, more opportunities for educating pharmacists will be made available to
      satisfy the vast need of the country. Development of clinical pharmacy services
      also will be expected to improve the quality of care provided.

PMID- 8251700
TI  - Possible phenytoin-ciprofloxacin interaction.

PMID- 8251701
TI  - Potential interaction between niacin and transdermal nicotine.

PMID- 8251702
TI  - Effect of hemodialysis on serum concentration of isepamicin in a patient with
      endstage renal failure.

PMID- 8251703
TI  - Bacterial resistance to antimicrobial agents--the time for concern.

PMID- 8251705
TI  - Health care reform: how informed is it?

PMID- 8251704
TI  - Comment: current treatment recommendations for leishmaniasis.

PMID- 8251706
TI  - Effective strategies and programs to increase minority participation in the
      health professions for the 21st century.
AB  - Efforts in the 1960s and early 1970s aggressively met the national health care
      challenge to increase minority enrollment in health professions schools. These
      efforts resulted from an academic and community-based collaboration supported by
      public and private funding. This review was undertaken to inventory the
      strategies and programs of that period and to highlight effective strategies. A
      literature review of minority program studies was conducted to catalog specific
      strategies and programmatic activities. Criteria used to evaluate effectiveness
      were also assessed. Publication of any studies and evaluations of these programs
      are limited; longitudinal studies are scarce. Evaluative criteria of that time
      combined quantitative and qualitative measures that were not applied uniformly
      and consistently. The inventory of programmatic activity ranged from career
      awareness days to establishment of health career "magnet" schools. The review
      found that three strategies--awareness development, enrichment/reinforcement, and
      prematriculation--were effectively applied in programs across all areas of the
      health professions studied, that is, MODVOPP (medicine, optometry, dentistry,
      veterinary science, osteopathy, podiatry, and pharmacy), nursing, and allied
      health. Today these strategies continue to be effectively applied, but the
      hostile social climate and dwindling funding threaten the progress made.
      Revitalization of past efforts is imperative.

PMID- 8251707
TI  - Enrichment programs to create a pipeline to biomedical science careers.
AB  - The Student Educational Enrichment Programs at the Medical College of Georgia in
      the School of Medicine were created to increase underrepresented minorities in
      the pipeline to biomedical science careers. Eight-week summer programs are
      conducted for high school, research apprentice, and intermediate and advanced
      college students. There is a prematriculation program for accepted medical,
      dental, and graduate students. Between 1979 and 1990, 245 high school students
      attended 12 summer programs. Of these, 240 (98%) entered college 1 year later. In
      1986, after eight programs, 162 (68%) high school participants graduated from
      college with a baccalaureate degree, and 127 responded to a follow-up survey.
      Sixty-two (49%) of the college graduates attended health science schools, and 23
      (18%) of these matriculated to medical school. Of college students, 504
      participated in 13 summer programs. Four hundred (79%) of these students
      responded to a questionnaire, which indicated that 348 (87%) of the 400 entered
      health science occupations and/or professional schools; 179 (45%) of these
      students matriculated to medical school. Minority students participating in
      enrichment programs have greater success in gaining acceptance to college and
      professional school. These data suggest that early enrichment initiatives
      increase the number of underrepresented minorities in the biomedical science
      pipeline.

PMID- 8251708
TI  - Spinal cord sarcoidosis: a case report and review of the literature.
AB  - Sarcoidosis is a multisystem syndrome characterized by the development of
      noncaseating granulomata. These lesions disrupt the architecture and function of
      the tissue in which they reside. Sarcoidosis in and around the spinal cord is
      relatively rare. This article discusses a patient with sarcoidosis who presented
      with progressive spinal cord compression. Neurosarcoidosis can occur with
      manifestations involving the cranial nerves, parenchymal brain tissue,
      neurohormonal axis of the base of the brain, spinal cord, or peripheral nerves.
      When the spinal cord is involved, it is most important to determine the location
      and confirm the diagnosis. Intramedullary lesions respond to medical therapy
      alone, if at all. Extramedullary lesions may be amenable to surgical resection
      with postoperative steroid therapy. If treated in time, patients with the latter
      form generally achieve a nearly full recovery.

PMID- 8251709
TI  - Enteroenteric fistula of the duodenum in a patient with AIDS and Mycobacterium
      avium-intracellulare infection.
AB  - Upper gastrointestinal endoscopy revealed a double lumen in the second portion of
      the duodenum in a 39-year-old man with advanced acquired immunodeficiency
      syndrome (AIDS). The lesion was not lined with an epithelium and improved with
      antituberculous therapy. These findings, as well as both an extensive transmural
      inflammation with foamy macrophages laden with acid-fast microorganisms and the
      destruction of the bowel wall, were consistent with Mycobacterium avium
      intracellulare infection, but not with congenital duplication. An upper
      gastrointestinal series was falsely negative. Deep, penetrating lesions and
      double-barreled lumen are not infrequent in AIDS-related esophageal disease. We
      propose that similar lesions related to M avium-intracellulare occur in the
      bowel, especially when immune impairment and mycobacterial infection are severe.
      Awareness of mycobacterial infections of the gut is important in the era of AIDS.

PMID- 8251710
TI  - Saying NO to cerebral ischemia.

PMID- 8251711
TI  - The effects of midazolam and sufentanil sedation on middle cerebral artery blood
      flow velocity in awake patients.
AB  - Midazolam and sufentanil are commonly used for sedation. Cerebrovascular effects
      of low-dose midazolam have not been studied previously, and cerebrovascular
      effects of sufentanil remain controversial. Forty ASA I and II patients were
      studied preoperatively. These patients were given midazolam (20 or 40
      micrograms/kg) or sufentanil (0.1 or 0.2 micrograms/kg) i.v. Transcranial Doppler
      recordings of middle cerebral artery mean blood flow velocity (Vm) were recorded
      before administration of the study drug and for the 5-min investigation period.
      Mean arterial pressure, heart rate, and end-tidal CO2 remained constant during
      the investigation and did not vary between treatment groups. Vm decreased 17 to
      21% with both midazolam doses (p < 0.05), returning to baseline within 5 min. Vm
      did not change with either sufentanil dose. These results suggest that midazolam
      decreases cerebral blood flow (CBF) by increasing cerebral vascular resistance
      (CVR). The low sedative doses of sufentanil used in this study did not affect Vm
      over 5 min in unanesthetized patients.

PMID- 8251712
TI  - Rectal nifedipine for the management of intraoperative hypertension.
AB  - The effect of rectal administration of nifedipine for the management of
      intraoperative hypertension was studied in 12 adult neurosurgical patients,
      physical status II and III. A rise in mean arterial pressure (MAP) of > 20 mm Hg
      over the preoperative value was taken as the point at which rectal nifedipine
      (150 micrograms kg-1) was administered. Onset of action of nifedipine was
      observed in 4.5 +/- 1.5 min (mean +/- SD) with a peak effect at 30.8 +/- 10.7
      min. MAP decreased from 124 +/- 4.5 mm Hg to 97 +/- 2.4 mm Hg. Heart rate and
      central venous pressure were unchanged. Endoscopic examination of the rectal
      mucosa 48 h after administration of nifedipine did not show any abnormality.
      Rectal nifedipine was found to be effective and safe for the management of
      intraoperative increases in arterial blood pressure as well as being convenient
      to administer to patients undergoing neurosurgical procedures.

PMID- 8251713
TI  - Low dose L-NAME reduces infarct volume in the rat MCAO/reperfusion model.
AB  - In a variety of recent studies, inhibitors of nitric oxide (NO) synthesis have
      ameliorated neuronal injury during permanent focal cerebral ischemia, suggesting
      that NO may contribute to ischemic damage. In other studies, however, these
      inhibitors increased infarct volume during permanent middle cerebral artery
      occlusion (MCAO). One complication in these studies was that high-dose NO
      synthase inhibitors increased mean arterial blood pressure (MAP) by 20-30 mm Hg.
      Thus, it is possible that variations in the effects of NO synthesis inhibitors on
      infarct volume could be related to effects of these inhibitors on MAP and
      cerebral perfusion during or after ischemia. The present study compared the
      effects of control (Ringer's lactate solution) versus low-dose NO inhibition (0.1
      mg/kg bolus followed by 0.01 mg/kg/min) on cerebral infarct volume using L-NAME
      (NG-nitro-L-arginine methyl ester) administered during a 1-h baseline period, 3-h
      of MCAO, and 2 h of reperfusion in the spontaneously hypertensive rat. Infarct
      volume was determined using the TTC (2,3,5-triphenyltetrazolium chloride) method
      performed 5 h after onset of occlusion. L-NAME reduced infarct volume by 55%. In
      the control group (n = 7), infarct volume measured 116 +/- 4 (SEM) mm3 which was
      29 +/- 1% of the left hemispheric volume (400.5 +/- 0.3 mm3). In the L-NAME group
      (n = 7), infarct volume measured 53 +/- 8 mm3 which was only 13 +/- 2% of the
      left hemispheric volume (400.4 +/- 0.5 mm3).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251714
TI  - Propofol combined with halothane or with fentanyl/halothane does not alter the
      rate of CSF formation or resistance to reabsorption of CSF in rabbits.
AB  - A previous study of the cerebral effects of propofol reported that the propofol
      caused an initial decrease of cerebrospinal fluid (CSF) pressure and cerebral
      blood flow, followed by a return of CSF pressure to control values despite
      continued administration of propofol and continued decrease of cerebral blood
      flow. One explanation for the return of CSF pressure to control values is that
      propofol may cause an increase of the rate of CSF formation or of resistance to
      reabsorption of CSF. The present study was designed to examine the effects of
      low, moderate, and high doses of propofol, given with either fentanyl or
      halothane, on the rate of CSF formation and resistance to reabsorption of CSF.
      The rate of CSF formation and resistance to reabsorption of CSF were determined
      in 12 rabbits using the technique of ventriculocisternal perfusion. In the
      propofol-fentanyl group (n = 6), the fentanyl dose was 100 micrograms/kg followed
      by 20 micrograms x kg-1 x h-1 i.v., and in the propofol-halothane group (n = 6),
      the concentration of halothane was 0.8 to 1.0%. For both groups, the three doses
      of propofol were 6 mg/kg followed by 12 mg x kg-1 x h-1, 24 mg x kg-1 x h-1, and
      48 mg x kg-1 x h-1 i.v., respectively. In both groups, propofol caused no
      significant change of the rate of CSF formation or resistance to reabsorption of
      CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251715
TI  - Cerebral blood flow autoregulation after experimental subarachnoid hemorrhage
      during hyperventilation in rats.
AB  - The purpose of the current study was to investigate whether impaired cerebral
      blood flow (CBF) autoregulation after experimental subarachnoid hemorrhage (SAH)
      could be restored by hyperventilation. SAH was induced in rats by injection of
      autologous blood into the cisterna magna. CBF was measured using intracarotid
      injection of 133Xe. Autoregulation was studied in four groups of animals:
      normoventilated controls, hyperventilated controls, normoventilated animals with
      SAH, and hyperventilated SAH animals. PaCO2 in the normocapnic groups was 38-42
      mm Hg and 25-30 mm Hg in the hypocapnic groups. CO2 reactivity after SAH was
      intact as hyperventilation decreased CBF by 38% in controls and by 46% in animals
      with SAH. Mean arterial pressure (MAP) was unaffected in both groups. In the
      controls, hypocapnia caused a shift of the autoregulation curve toward lower CBF
      levels without changing the lower limit of autoregulation. In the SAH group in
      the normocapnic state, autoregulation was absent as the obtained curve was a
      straight line, such that CBF increased with increasing MAP. However, during
      hypocapnia CBF was constant in the MAP interval between 60-150 mm Hg showing
      reestablishment of autoregulation by hyperventilation.

PMID- 8251716
TI  - Endotracheal tube obstruction during stereotactic craniotomy.
AB  - The authors present a case of endotracheal tube (ETT) obstruction during
      stereotactic computer-assisted volumetric resection of an enlarging left thalamic
      mass in a prone patient. The head was fixed in a stereotactic COMPASS head frame
      and the patient positioned on transverse hip and shoulder rolls. The prone
      position was achieved with attention given to ensure an adequate distance between
      the sternum and mentum. At the time of dural incision, the patient's peak airway
      pressure and end-tidal CO2 tension increased markedly whereas the O2 saturation
      remained stable at 99%. It immediately became clear that the patient's torso had
      moved cephalad resulting in ETT obstruction, despite the continued integrity of
      head fixation. We emphasize the need for proper and safe patient positioning, the
      placement of a bite block between the molar teeth, and particularly in obese
      patients, the need to tape the patient's torso securely to the operating room
      table. In addition, it may be necessary to place the operating room table in
      reverse Trendelenberg position to prevent cephalad movement of the torso. This
      case represents an unusual mechanism of ETT obstruction, as normally the latter
      is caused by flexion of the head rather than by cephalad movement of the torso.

PMID- 8251717
TI  - Audiorespiratory modes of communication in the critical care unit.

PMID- 8251718
TI  - [Pathophysiological basis of 3 subtypes in ganfeng neidong syndrome].
AB  - The multiple parameters of 3 Subtypes: Ganyang Huafeng Syndrome (GYHFS), Xuexu
      Shengfeng Syndrome and Yinxu Fengdong Syndrome of Ganfeng Neidong Syndrome were
      determined for the 1st time. It was found that there were several characteristics
      in GYHFS. (1) Disturbance of the cerebral blood flow and the damage of brain
      tissue was manifested by the abnormality of the bulbar conjunctival
      microcirculation, carotid Doppler ultrasonic determination and brainstem auditory
      and visual pathway, high blood viscosity, dysmnesia, free radical and lipid
      peroxidation injury and the changes of Zn, Cu, K and Mg after brain damage. (2)
      Stress status were expressed by the high plasma levels of cortisol,
      norepinephrine and epinephrine, decreased serum triiodothyronine level and
      hyperfunction of sympathetic nerve. (3) The marked changes of the regulating
      substance of the vessel smooth muscle function including the increased plasma
      levels of TXB2, TXB2/6-k-PGF1 alpha, and calmodulin, as well as decreased SP,
      ANP, CGRP. Other 2 subtypes had about the same changes of these parameters, but
      of milder disorders.

PMID- 8251719
TI  - [Xuefu zhuyu decoction in treating blood stasis syndrome of schizophrenia].
AB  - The clinical and experimental study of 66 schizophrenics were conducted. Based on
      mental symptoms, four-diagnostic method of TCM and hemorheology, it presented
      preliminarily the clinical and experimental criteria for schizophrenia. The
      combined therapy of Xuefu Zhuyu Decoction and low dosage of antipsychotic drug
      could relieve the mental symptoms and the abnormal hemorheologic index
      normalized. Its therapeutic index was higher than that of control group.

PMID- 8251720
TI  - [Effect of photosensitized oxidation auto-hemotherapy with buyang huanwu tang on
      sequela of apoplexy].
AB  - An effective therapy in treating sequela of apoplexy (SA) was reported, 115
      patients were divided semi-randomly into three groups: group T for treatment,
      both group A and B for control. Patients in group T received Photosensitized
      Oxidation Auto-Hemotherapy (POAH) with Buyang Huanwu Tang therapy, group A
      received POAH only, while in group B, conventional treatment were conducted.
      Clinical data were collected based on pre- and post-treatment qualified
      procedures according to "The Advice For Clinical Study on Apoplexy", complemented
      by hemorheologic findings and examination of nail fold microcirculation. The
      results showed that there was significant difference between group T and group A
      or B (P < 0.05), among them, the effective rate in group T was 78.5%. Differences
      in hemorheology findings and examination of nail fold microcirculation were
      similar (P < 0.01).

PMID- 8251721
TI  - [Controlled observation on naoxuenin in treating 22 hypertensive encephalorrhagia
      patients].
AB  - 42 cases of hypertensive encephalorrhagia (HER) were randomly divided into two
      groups. All cases received treatment within three days after the attack, group I
      received current conventional treatment as control, group II took 100ml Naoxuenin
      (NXN) oral liquid with conventional treatment. Effects were evaluated after 14
      day treatment. Results indicated that NXN had direct therapeutic effect or/and
      synergistic effect on HER in acute phase, the mortality was significantly lowered
      (P < 0.05) and the recovery of nerve function speeded up in group II. And NXN
      displayed similar effect on different Syndromes and Types of the acute phase of
      HER (P > 0.05). Analysis of results of hemorheological examination of pre- and
      post-treatment suggested that NXN could improve the microcirculation and prevent
      the high hemo-viscosity syndrome caused by dehydration therapy.

PMID- 8251722
TI  - [Comparison between electro-acupuncture with chlorpromazine and chlorpromazine
      alone in 60 schizophrenic patients].
AB  - 60 schizophrenia patients were treated with electro-acupuncture and
      chlorpromazine therapy in comparison with chlorpromazine therapy alone, 30
      patients for each group, and their curative effects evaluated according to the
      brief psychiatric rating scale (BPRS). The result showed the total curative
      effects of the two groups were similar. However, the marked effects appeared
      earlier in combined therapy than that of using chlorpromazine alone, less
      chlorpromazine was needed, hence displayed fewer side-effects.

PMID- 8251723
TI  - [Treatment of myelodysplastic syndrome by combined traditional Chinese medicine
      and Western medicine therapy].
AB  - 50 cases were treated with Myelodysplastic Syndrome (MDS) by combined TCM-WM
      therapy. They were classified into RA 17 cases, RAS 6, RAEB 19, CMML 1 and RAEBT
      7. The patients were divided into two groups, one with RA and RAS receiving
      treatment of hemopoietic and immune drugs plus Chinese medicinal herbs, the other
      with RAEB, CMML and RAEBT receiving treatment of LD Ara-c and LD Hom chemotherapy
      plus medicinal herbs. The effective rates were 47.83% and 62.96% respectively,
      the total effective rate being 56%. 6 cases (RAEB 4, RA 1, RAS 1) were treated
      with all-trans retinoic acid used as an inducer of differentiation, 2 of them
      were effective. 11 patients with MDS who had transformed into acute leukemia were
      treated by LD Ara-c and combined TCM-WM chemotherapy, the remission rate was
      54.55% and the survival period was 9-27 months after remission. In some cases low
      dose chemotherapy resulted in hemocytopenia, bone marrow inhibition, infection,
      mild nausea and anorexia.

PMID- 8251724
TI  - [Effect of qigong on blood pressure and life quality of essential hypertension
      patients].
AB  - 56 essential hypertension patients (stages I, II) received Qigong from Mar, 1989
      to Sept, 1991, pre- and post-treatment comparison of BP and life quality (LQ)
      indices revealed that (1) It could efficiently lower BP(P < 0.001). Stroke,
      congestive heart failure and acute myocardial infarction did not occur. No side
      effects were observed as well. (2) It could markedly improve LQ of hypertensive
      patients. LQ examinations showed that significant difference (P < 0.001) existed
      among LQ indices except dysfunction, which might be due to the selection of non
      dysfunctional patients. LQ should be widely used in clinical practice and medical
      research.

PMID- 8251725
TI  - [Effect of qigong on plasma coagulation fibrinolysis indices of hypertensive
      patients with blood stasis].
AB  - The levels of plasma tissue-type plasminogen activator (tPA), plasminogen
      activator inhibitor (PAI), VIII factor related antigen (VIIIR:Ag) and anti
      thrombin (AT-III) were determined in 40 hypertensive patients with Blood Stasis.
      The results indicated that the function of coagulation-fibrinolytic system was
      disturbed. After one year of practising Qigong, plasma PAI and VIII R:Ag levels
      were decreased, while plasma tPA and AT-III levels increased. It suggested that
      Qigong could improve the function of coagulation-fibrinolytic system.

PMID- 8251726
TI  - [Experimental study of Ligusticum wallichii on cerebrovascular hemodynamic
      parameters].
AB  - The model of experimental atherosclerosis was established by means of dietary
      hyperlipidemia and repeated intravenous injection of heterologous serum to make
      the immunologic injuries of arterial endothelium, in which the effect of
      Ligusticum wallichii (LW) on the cerebrovascular hemodynamic parameters (CVHP)
      was observed. All CVHP indexes in LW group were near that of normal group, and
      there was no significant difference between these two groups. The carotid
      arteries' mean flow (Qmean), mean velocity (Vmean), maximal velocity (Vmax),
      cerebrovascular peripheral compliance for zero pressure and cerebrovascular
      peripheral resistance (R) in LW group were significantly better than that of
      atherosclerotic control group (P < 0.05-0.01). The results showed that LW had
      protective effects on cerebral vessels.

PMID- 8251727
TI  - [Effect of xiao chaihu decoction on experimental alkaline reflux gastritis in
      rats].
AB  - The effects of Xiao Chaihu Decoction (XCHD) on alkaline reflux gastritis and
      gastric secretion in rats was observed. RESULTS: (1) 5g/kg, 20 g/kg of XCHD might
      markedly inhibit the gastric lesion induced by gastric feeding of sodium
      taurocholate; (2) 5g/kg, 20g/kg of XCHD might significantly prevent the gastric
      lesion induced by gastric feeding of intestinal juice; (3) On chronic reflux
      gastritis model induced by spring-expanded pylorus after 4 or 8 weeks, 4g/kg
      20g/kg of XCHD might lower the incidence of gastritis, and reduce the
      intragastric bile acid; (4) 5g/kg and 20g/kg of XCHD might significantly inhibit
      the secretion of gastric juice and acid as well as the activity of pepsin. The
      results suggested that XCHD had anti-reflux gastritis effect.

PMID- 8251728
TI  - [Prophylactic and therapeutic effect of jiawei zhigancao tang injection on
      experimental arrhythmia in rats].
AB  - The antiarrhythmic effect of Jiawei Zhigancao Tang injection (JZTI) was studied
      in experimental arrhythmia induced by aconitine or by CaCl2 in anesthetized rats.
      The prophylactic dose of JZTI (5g/kg, i.v.) reduced the incidence rate of
      premature ventricular complexes, ventricular tachycardia (P < 0.01), delayed the
      onset time of arrhythmia induced by CaCl2 (P < 0.01), and the recovery time of
      sinus rhythm occurred earlier than that of control group (P < 0.01). The
      therapeutic dose of JZTI (10g/kg, i.v.) raised the rate of aconitine-induced
      arrhythmia to sinus rhythm conversion (P < 0.05). The results showed that JZTI
      could significantly antagonize arrhythmia induced by aconitine or by Cacl2 in
      rats.

PMID- 8251729
TI  - [Experimental study on effect of jiawei yupingfeng san on microcirculation and
      plasma superoxide dismutase activity in old mice].
AB  - The effects of Jiawei Yupingfeng San on microcirculation and plasma SOD of old
      mice were observed. The results showed that the prescription could markedly
      improve old mice's blood flow of microcirculation, increase their speed of blood
      flow and raise their plasma TSOD and Cu, Zn-SOD activity, and there was very
      significant difference compared with control (P < 0.001). The results suggested
      that this prescription had the effects of improving the quality of life and
      delaying the aging of organism.

PMID- 8251730
TI  - [Effect of youjiangzhi capsule on senile hyperlipidemia].
AB  - 61 aged with hyperlipidemia were randomly divided into treatment and control
      group according to the ratio of 2:1, which were treated with Youjiangzhi capsule
      and Mai-an Powder respectively. After 8 weeks of administration, all of the four
      indexes of blood lipid (TC, TG, HDL-C, TC-HDL-C/HDL-C) were significantly
      improved in both groups, but the effective rate of TC-HDL-C/HDL-C was much better
      in treatment group than that in control. The result showed that there was a good
      effect of Youjiangzhi Capsule on the senile hyperlipidemia.

PMID- 8251731
TI  - [Absorptive capacity of upper gastrointestinal tract with Chinese herbal
      medicine].
AB  - 285 reports on the intoxication of Chinese herbal medicine per os were reviewed.
      The toxic symptoms occurred after oral administration for less than 10 min in
      about 110 reports. Some components of these herbal medicines might be absorbed
      and then reach effective level more rapidly. By segmental ligation of GI tract,
      experiments in rabbits, cats, rats or mice were conducted, in which principal
      ingredients of Rheum palmatum, Coptis chinensis, Veratrum nigrum, and aconitine
      were absorbed in esophagus or stomach within short period of time was observed.
      It suggested that the absorptive capacity of upper GI tract might have universal
      significance. The treatment of acute diseases by oral administration of Chinese
      herbal medicines is feasible.

PMID- 8251732
TI  - [Effect of Astragalus membranaceus on cardiovascular system].

PMID- 8251733
TI  - [The layers of the gallbladder wall: an ultrasound-anatomic comparative study].
AB  - In a sonographic-histological comparative test, operatively withdrawn
      gallbladders in native and formol-fixed states were examined. The thickness of
      the gallbladder wall and of its layers was measured sonographically. Afterwards
      the gallbladders were reexamined microscopically in the sonographic sectional
      plane and the measurement was repeated. By removal of the single layers of the
      wall and by repeated sonographic measuring, sonographic and microscopic
      measurements of the parietal layers could be correlated. Both gallbladder wall
      thickness and thickness of the single anatomic layers can be evaluated
      sonographically. The correlation between sonographic and histological
      measurements is fairly to highly significant. The sonographically measurable
      layers can be related to the following anatomical layers (when measuring from
      outwards to inwards): 1. echogenic layer = initial echo and subserosa; 2. echo
      poor layer = muscularis; 3. echogenic layer = lamina propria; 4. echo-poor layer
      = mucosal epithelium; 5. echogenic layer = exit echo.

PMID- 8251734
TI  - [Quantitative determination of echogenicity of diffuse inflammatory thyroid gland
      diseases].
AB  - Grey level was measured in 93 ultrasonic scans of the thyroid gland in order to
      quantify hypoechogenicity in diffuse inflammatory thyroid disease. Using a modern
      ultrasound device (256 grey-scale steps and 7.5-MHz parallel scan), grey levels
      were measured in normal thyroid glands and euthyreotic goiters as well as in
      thyroiditis or Graves' disease using a programmed setting of the device. Highly
      significant differences were found between normal thyroid glands and thyroiditis
      or Graves' disease. Sensitivity of the method was 65% in discriminating Graves'
      disease and 91% in discriminating thyroiditis; specificity was 95%. The clinical
      value of the method for follow-up studies in inflammatory diseases of the thyroid
      gland still has to be established.

PMID- 8251735
TI  - [Pseudoaneurysms of the femoral artery--noninvasive diagnosis and compression
      therapy].
AB  - In 8 patients with pseudoaneurysms of the femoral artery, diagnosis and possible
      nonsurgical treatment is presented: After primary clinical diagnosis and color
      Doppler or angiographic confirmation, aneurysms of less than 5 cm in diameter are
      treated by manual or color Doppler-supported compression. Within 9 to 36 min the
      lumen is occluded, remaining closed even in controls up to 12 months.

PMID- 8251737
TI  - [Ultrasound of incidental tumors of the adrenal gland and endocrine
      hypertension].
AB  - We report on a retrospective analysis of 1,500 hypertensive patients who
      underwent a sonographic examination of the abdomen. 8 'incidentalomas' of the
      adrenal gland (0.6%) were thereby found. Endocrinological analysis showed that
      only 1 of the incidentalomas was active (pheochromocytoma). The other tumors had
      no endocrine activity. On the other side, 7 patients without any sonographic
      abnormality had hyperaldosteronism, 1 patient suffered from an adrenomedullary
      hyperplasia. Those patients had been thought to have endocrine hypertension from
      clinical suspicion. We conclude that a thorough sonographic examination of the
      adrenal area is an important part of the diagnostic workup in hypertensive
      patients, although most of the incidentally discovered tumors are
      endocrinologically inactive. Adrenocortical and adrenomedullary hyperplasias and
      adrenocortical adenomas are detected clinically while they are still not visible
      by ultrasound.

PMID- 8251736
TI  - Diagnostic value of color Doppler sonography in primary liver tumors--a trend
      study.
AB  - In order to investigate the diagnostic value in differential diagnosis of primary
      liver tumors, color Doppler sonography was used preoperatively in 30 patients.
      Without difference, tumor hypervascularization was found in patients with
      hepatocellular carcinoma (2 of 4), cholangiocellular carcinoma (4 of 4),
      hemangioma (3 of 8), focal nodular hyperplasia (8 of 8), adenoma (3 of 4), and
      neuroendocrine tumor (n = 1). No vascular signal could be detected in 1 case of
      adenomatous hyperplasia and 2 cases of hepatocellular carcinoma, one after
      previous chemoembolization. Hemangioma appeared hypo- or even avascular in 5 of 8
      patients. Therefore, according to our experience, the yield of color Doppler
      sonography is rather low for differential diagnosis and prediction of the tumor
      dignity. With regard to the surgical procedure, valuable information about tumor
      extension can be obtained particularly in central lesions close to hilar
      structures or liver vein confluence. Further indications result from follow-up of
      tumor vascularization after chemoembolization and chemotherapy.

PMID- 8251738
TI  - Extracardiac 'hot' and 'cold' areas on thallium-201 myocardial SPECT imaging.
AB  - A 72-year-old man underwent Persantine 201Tl myocardial SPECT imaging that showed
      a transient area of extracardiac radiotracer accumulation inferior to the
      inferior wall of the left cardiac ventricle, and a persistent, rounded, cold area
      in the liver. CT of the abdomen confirmed a cystic lesion in the liver
      corresponding to the cold area, and the transient extracardiac tracer
      accumulation area corresponded to a large aneurysm of the distal descending
      thoracic aorta. An extracardiac abnormal area of 201Tl localization, 'hot' or
      'cold', should be included for scan interpretation to depict thoracic and/or
      upper abdominal lesions(s).

PMID- 8251739
TI  - [Recent aspects in diagnosis and therapy of esophageal varices].
AB  - Esophageal varices are of ominous significance in patients with cirrhosis.
      Diagnostic procedures are undertaken for evaluation of the bleeding risk. Whereas
      after a recent bleeding event the risk of rebleeding is high (up to 70%) and
      rebleeding prophylaxis is obligatory, the risk of first bleeding in patients who
      never bled depends on the presence of bleeding risk indicators. Endoscopy is the
      most powerful tool for assessment of the bleeding risk. Variceal size, the
      presence of the red color sign and the presence of concomitant fundic varices
      indicate a high risk of first bleeding. Currently used endoscopic or medical
      prophylaxis has a high rate of failure. On the other hand, operative measures
      prevent bleeding in most patients. However, the perioperative morbidity and
      mortality is high. Controlled studies will show whether the patients will benefit
      from new experimental treatment approaches (endoscopic obliteration of varices,
      endoscopic ligation of varices, TIPS and liver transplantation.

PMID- 8251740
TI  - [Transjugular liver puncture].
AB  - The transjugular liver biopsy is a method which allows assessment of hepatic
      tissue from patients with contraindications against classical percutaneous
      biopsy. A catheter with a long biopsy needle within is inserted into the jugular
      vein and then pushed forward through the Vena cava into a hepatic vein in order
      to carry out the biopsy of the liver. Indications for this examination are
      biopsies in patients with considerably impaired coagulation or tense ascites. It
      is possible, if necessary, to measure free and wedged pressure within the liver
      veins during this examination. On average, in 93% of all examinations enough
      tissue is yielded to allow for satisfactory judgement of histological changes;
      the rate of success is little less than that with percutaneous biopsies. However,
      considering all aspects, this technique gives good results. Lethal complications
      are rare (0.17%); the total complication rate is about 12%, 0.5-2.7% are severe.
      Although this method needs more time and technical equipment than percutaneous
      biopsy, the procedure has to be considered as an important technique for the
      evaluation of terminal liver disease.

PMID- 8251741
TI  - [Endosonography of the gastrointestinal tract--an assessment of current status].
AB  - Endoscopic ultrasound (EUS) combines endoscopy and ultrasonography. A small
      ultrasonic transducer incorporated into the rigid tip of endoscopes is
      transported into certain regions of the upper and lower gastrointestinal (GI)
      tract under visual control. The method allows for a high-resolution imaging of
      the gastrointestinal wall and organs and structures in its immediate vicinity.
      This is especially valuable in the preoperative local staging of gastrointestinal
      malignancies (esophagus, stomach, pancreas, biliary tract, colon and rectum)
      according to the new TNM system. In patients without distant metastases EUS helps
      guiding treatment decisions. EUS is also used with clinical benefit in the
      diagnosis of submucosal tumors and in the preoperative localization of pancreatic
      endocrine tumors. Its role in the diagnosis and management of benign
      gastroenterological disorders has still to be established.

PMID- 8251742
TI  - [Percutaneous endoscopic gastrostomy].
AB  - Probes for the percutaneous endoscopic gastrostomy (PEG) are placed by pull
      through methods or by direct puncture of the stomach. Depending on the length of
      the interior branch of the probe, gastral or (duodeno-) jejunal feeding is
      possible; the latter may also be achieved by direct percutaneous endoscopic
      jejunostomy (PEJ). Small calibre endoscopes can be introduced via large-bore PEG
      probes; after the extraction of such a probe the resulting fistulous tract itself
      may also be used fur percutaneous endoscopy by using pediatric endoscopes. The
      usual external fixation of the probes with compresses fixed by sticking plaster
      creates a humid chamber favouring the growth of bacteria. This can be avoided by
      an open well-aired fixation using a ring. Indications for the probes are
      prolonged enteral feeding in patients enable to swallow or to consume adequate
      nutrition orally, decompression in gastrointestinal obstruction, instillation of
      percutaneously drained bile and percutaneous endoscopy, e.g. for repeated
      retrograde laser application as a palliative treatment in patients with tumour
      obstruction of the oesophagus. Complications due to PEG/PEJ probes are relatively
      rare; severe are aspiration in cases of gastro-oesophageal reflux and
      peritonitis.

PMID- 8251743
TI  - [Shockwave therapy of gallstones].
AB  - Extracorporeal shock-wave lithotripsy (ESWL) is a helpful adjunct for those bile
      duct stones which cannot be extracted by routine endoscopic measures including
      mechanical lithotripsy. For very large or impacted stones in the bile duct or
      stones in the intrahepatic biliary tree, and also for stones located in proximity
      to a bile duct stenosis, shock-wave therapy has proven to be safe and successful.
      More than 85% of the patients become free of stones after this therapy; they
      otherwise would have had to undergo high-risk open bile duct surgery. For
      gallbladder calculi, the pivotal factor for complete fragment disappearance after
      shock-wave therapy is sufficient stone disintegration. Only if fragments not
      larger than 3 mm are achieved, complete expulsion and/or dissolution of these
      fragments may be expected in a high percentage of the patients. Optimal
      candidates include patients with a single, radiolucent stone in a well
      contracting gallbladder. For this group, ESWL is a safe and effective noninvasive
      therapeutic alternative.

PMID- 8251744
TI  - [Peroral and percutaneous transhepatic cholangioscopy].
AB  - Cholangioscopy, in conjunction with histological examinations, yields diagnostic
      information in unclear biliary diseases in addition to conventional indirect
      imaging methods. Unclear stenoses and protruded lesions can be differentiated,
      and the preoperative staging can probably be improved due to an exact mapping of
      the intraductal extension of bile duct lesions. Cholangioscopic electrohydraulic
      lithotripsy or laser treatment of stones not amenable to routine endoscopy are
      highly effective and safe alternatives to surgery. The peroral technique promises
      a rapid visualization of the biliary tree, provided that the papilla can be
      approached adequately. The retrograde access to lesions above the bifurcation or
      upstream from strictures is limited. In contrast, the more time-consuming
      percutaneous transhepatic cholangioscopy can be performed even in patients with a
      difficult anatomy, retrogradely inaccessible bile duct stenoses or intrahepatic
      calculi. However, this approach should be limited to cases not amenable to
      peroral techniques, because the creation of the cutaneo-biliary fistula is not
      without risks.

PMID- 8251745
TI  - Enhanced expression, secretion, and large-scale purification of recombinant HIV-1
      gp120 in insect cell using the baculovirus egt and p67 signal peptides.
AB  - The expression of glycosylated and secreted recombinant mammalian proteins in
      baculovirus-infected insect cells is often much less efficient than that of other
      foreign proteins in this system. In an effort to improve the expression and
      secretion of such proteins we have constructed baculovirus vectors which contain
      the signal peptide coding regions from two baculovirus proteins, an ecdysteroid
      UDPglucosyltransferase (egt) and the envelope glycoprotein gp67. We used these
      vectors to express HIV-1 gp120, inserting the baculovirus signal peptides in
      place of the HIV-1 envelope signal peptide. When Sf9 cells infected with
      recombinant baculoviruses made from these vectors (vegt120 and vp67120) were
      compared with cells infected with the normal gp120 baculovirus a 6- to 20-fold
      increase in expression and secretion of gp120 was observed. When the HIV-1 signal
      peptide was used only 40% or less of the total gp120 produced in Sf9 cells was
      secreted. However, using the egt or p67 signal peptides, up to 70% of the total
      gp120 produced was secreted. Therefore, not only was more gp120 produced from
      these modified viruses but secretion of gp120 was more efficient. Large-scale
      expression and purification of egt-gp120 from a 5-liter airlift fermenter or a 6
      liter spinner flask resulted in a yield of 10 to 15 mg of purified protein per
      liter. Using these baculovirus-derived signal peptides in baculovirus expression
      vectors is thus likely to aid in increasing expression and yield of heterologous
      secreted proteins in insect cells.

PMID- 8251746
TI  - High-level expression and purification of human leukotriene A4 hydrolase from
      insect cells infected with a baculovirus vector.
AB  - Leukotrienes constitute a group of bioactive compounds derived from arachidonic
      acid which play important roles in immediate hypersensitivity and inflammation.
      Leukotriene A4 hydrolase (LTA4H) is an epoxide hydrolase, catalyzing the
      hydration of LTA4 to LTB4, and also acts an aminopeptidase, with the ability to
      cleave amides of p-nitroaniline. The cDNA for LTA4H was cloned using
      oligonucleotide-directed amplification of the cDNA sequence by polymerase chain
      reaction and by oligonucleotide-based screening of a bacteriophage lambda gt11
      cDNA library derived from human placental tissue. High levels of biologically
      active LTA4H were expressed in cultured Spodoptera frugiperda insect cells
      infected with a baculovirus expression vector containing the LTA4H cDNA.
      Expression levels were approximately 100 mg per liter of cell-free culture media.
      LTA4H was recovered from the medium and purified to > 95% purity by ion-exchange
      and gel-filtration chromatography, with an overall yield of 76%. LTA4H produced
      by insect cells exhibits both hydrolase and aminopeptidase activities and has
      kinetic properties similar to those reported for enzyme isolated from human lung.
      Two major isoforms, with pI's of 5.3 and 5.1, were isolated by preparative
      chromatofocusing chromatography. NH2-terminal sequence analysis revealed that the
      two different by an NH2-terminal blocking group. Electrospray ionization mass
      spectrometry indicates that the two isoforms differ by a molecular mass of 42,
      indicating that the blocking group is an acetyl group.

PMID- 8251747
TI  - Overexpression of HIV-1 proteins in Escherichia coli by a modified expression
      vector and their one-step purification.
AB  - A synthetic expression system, pMH, was constructed for high-level expression and
      rapid purification of HIV-1 proteins in Escherichia coli, by introducing two
      synthetic sequences. The first sequence permitted a high-level expression via a
      second ribosome-binding site plus an A/T-rich region. This minicistron between
      the 5' untranslated region of the mRNA and the protein-coding region minimized
      the formation of local secondary structures and favored ribosome binding. The
      second region coded for six histidines, which allowed for easy purification of
      the proteins. Purification was based on interaction of the protein with metal
      ions: immobilized metal affinity chromatography. The p17 and p24 structural genes
      of HIV-1 were cloned into this modified expression vector. Expression of the
      structural proteins represented up to 30% of the total protein in E. coli, i.e.,
      40 mg of highly purified protein could be obtained per liter of culture.

PMID- 8251748
TI  - Expression of human milk beta-casein in Escherichia coli: comparison of
      recombinant protein with native isoforms.
AB  - Studies on physiological function and on structure-function relationships of
      human milk beta-casein have been limited. In this study, we have introduced the
      human beta-casein cDNA into vectors designed for expression in Escherichia coli.
      The inducible T7-based expression system resulted in high-level expression of
      recombinant beta-casein. The recombinant beta-casein, localized intracellularly
      in E. coli, was purified to homogeneity and compared with purified native beta
      casein, in particular with respect to phosphorylation. The E. coli-produced beta
      casein was found to comigrate with the full-length, nonphosphorylated native
      human beta-casein isoform on SDS-PAGE. An N-terminal peptide containing all
      tentative phosphorylation sites was isolated from the recombinant protein and
      analyzed by mass spectrometry. The molecular mass as well as the migration of
      this peptide on reversed-phase chromatography confirmed that it was
      unphosphorylated.

PMID- 8251749
TI  - Identification and purification of a human liver cytosolic tocopherol binding
      protein.
AB  - We recently purified rat tocopherol binding protein (TBP), a 32-kDa cytosol
      protein which specifically binds alpha-tocopherol, exists as two charge isoforms,
      and is expressed exclusively in liver and only in hepatocytes. For the present
      work, we sought to identify the human hepatic tocopherol binding protein from
      normal human livers harvested from organ donors. Gel filtration of hepatic
      cytosol identified a peak of [alpha-3H]-tocopherol binding in the 30- to 40-kDa
      fractions displaceable by excess unlabeled alpha-tocopherol. The fractions
      exhibiting this binding were pooled and run on Affi-Gel Blue affinity
      chromatography eluted with a salt gradient. A single major peak of tocopherol
      binding activity eluted at 22 mS/cm. This peak was further purified by FPLC
      chromatofocusing. A single protein peak of specific alpha-tocopherol binding
      eluted at pH 5.9. Finally, the peak from chromatofocusing was purified to
      apparent homogeneity by reversed-phase microbore HPLC chromatography. Two closely
      eluting protein peaks were separated and each was homogeneous, had identical
      migration on a SDS-PAGE (36 kDa), and had the same amino acid composition. The
      purified human TBP exhibited displaceable, specific alpha-tocopherol binding in
      the gel filtration assay of tocopherol binding. Laser desorption time-of-flight
      mass spectroscopy revealed a molecular weight of 36.6 kDa. Both forms of human
      TBP reacted in Western blot with polyclonal rabbit anti-rat TBP. Identification
      of the human tocopherol binding protein will allow future studies on its
      physiological function in human alpha-tocopherol metabolism.

PMID- 8251750
TI  - Analysis of the tyrosine protein kinase p56lck expressed as a glutathione S
      transferase fusion protein in Spodoptera frugiperda cells.
AB  - A baculovirus vector system that expresses cloned DNA sequences as glutathione S
      transferase fusion proteins was developed. This system was used to express and
      purify the lymphocyte-specific tyrosine kinase p56lck. This recombinant p56lck
      was purified to homogeneity in a single chromatography step using glutathione
      resin. By SDS gel analysis recombinant p56lck was found to migrate as two species
      with molecular masses of approximately 56,000 Da. p56lck purified in this manner
      retained a high level of activity, phosphorylated an exogenous substrate on
      tyrosine residues, and underwent autophosphorylation on tyrosine residues. The Km
      (approximately 0.33 mmol) and Vmax (approximately 83 pmol min-1 mg-1) values were
      also determined by using enolase as a substrate.

PMID- 8251751
TI  - Rapid purification of cationic granule proteases: application to human granzymes.
AB  - This report describes a simple scheme for the simultaneous purification of
      cationic human granzymes A, B, and 3 from human interleukin 2 (IL-2)-activated
      lymphocytes. The process, which requires approximately 8 h, includes: (1) cell
      cavitation, (2) two centrifugation steps, (3) four granule solubilization steps,
      and (4) cation-exchange chromatography. Granule solubilization consists of three
      extractions with a hypotonic buffer (25 mM NaCl) that contained Triton X-100
      followed by a final extraction in hypertonic detergent-free buffer (390 mM NaCl).
      We recovered approximately 35% of the trypsin-like (tryptase) activities mediated
      by granzymes A and 3, respectively, and approximately 25% of the asp-ase activity
      of granzyme B. The granzymes were identified after elution from the Mono S column
      by Western blot with a polyclonal antibody that reacts with a conserved amino
      acid sequence (9-16) of lymphoid/myeloid serine proteases. By amino-terminal
      sequencing, eluted granzyme A and B were indeed homogeneous. Granzyme 3, although
      highly enriched, appears to be contaminated with an uncharacterized granzyme.
      Although we have developed this scheme to rapidly isolate the granzymes, the
      procedure should assist the purification of secretory granule-associated cationic
      proteins that reside in neutrophils and mast cells as well as other cells that
      possess secretory function.

PMID- 8251752
TI  - Immunoaffinity chromatographic purification of Russell's viper venom factor X
      activator using elution in high concentrations of magnesium chloride.
AB  - RVV-X, the factor X activator from Russell's viper venom, has been isolated using
      affinity chromatography on agarose columns of a monoclonal antibody specific for
      this enzyme. Upon testing acid, alkaline, and high concentrations of MgCl2 for
      elution, it was found that use of high concentrations of MgCl2 was most effective
      in elution of RVV-X. It was nondenaturing and yielded 90% recovery of homogeneous
      enzyme without measurable contamination by other proteins of the venom.

PMID- 8251753
TI  - A tightly regulated system for overproduction of bacteriophage T4 lysozyme in
      Escherichia coli.
AB  - Bacteriophage T4 lysozyme has been purified using the Ni-chelate affinity
      chromatography technique from overexpressing Escherichia coli cells by fusion to
      an N-terminal 6x His tail. Regulation of the lysozyme gene expression has been
      found to be critical during growth phase of the bacteria by comparing different
      plasmid constructions. Whereas a tac-promoter fusion construct alone did not lead
      to efficient production of T4 lysozyme because of early cell lysis, an improved
      repressor sequence and co-overproduction of the tac repressor resulted in high
      level synthesis of the foreign protein after IPTG induction. Purification of the
      fusion protein from autolyzed crude cell extracts is possible in a simple one
      step procedure.

PMID- 8251754
TI  - Concomitant preparative isolation of calmodulin and heat shock protein (hsp90)
      from bovine testes.
AB  - We have described a convenient procedure for isolating large amounts of both
      calmodulin and the 90-kDa heat shock protein (hsp90) from bovine testes. These
      two proteins coeluted from phenyl-Sepharose during calcium-dependent hydrophobic
      interaction chromatography. The hsp90 was separated from calmodulin by gel
      filtration, purified by reverse-phase HPLC or lectin affinity chromatography, and
      identified by N-terminal amino acid sequence and immunoblotting with hsp90
      specific monoclonal antibody. The N-terminus of bovine hsp90 shared 93% amino
      acid identity with the murine alpha-isoform of hsp90. A third major testes
      protein of 97 kDa was also isolated with this protocol and was found to be
      homologous to the 94-kDa glucose-regulated protein.

PMID- 8251755
TI  - Overproduction and purification of sigma 32, the Escherichia coli heat shock
      transcription factor.
AB  - This paper reports the overproduction and the details of a rapid method to purify
      active sigma 32 that is free of core RNA polymerase enzyme. Maximal
      overproduction of sigma 32 in a T7 RNA polymerase-based expression system is
      achieved only in the presence of rifampicin. This 2-day procedure involves
      solubilizing inclusion bodies in Sarkosyl, removal of Sarkosyl by dialysis, and a
      single S-Sepharose column chromatography step. The final yield of sigma 32 is
      about 4.1 mg of approximately 95% purity from 1 g of wet weight cells.

PMID- 8251756
TI  - A procedure for the purification of thioredoxin-m from leaves of the C4 plant Zea
      mays.
AB  - A simple four-step procedure for the purification of thioredoxin-m from Zea mays
      leaves is described. The procedure provides pure protein with recoveries of 20
      25%. This thioredoxin mediates in the regulation of NADP-malate dehydrogenase
      involved in photosynthesis in C4 plants.

PMID- 8251757
TI  - Cofactor identification of threonine-serine dehydratase from sheep liver.
AB  - L-Threonine-serine dehydratase catalyzes the conversion of L-threonine and L
      serine to alpha-ketobutyric acid and pyruvate, respectively. The enzyme has been
      purified to homogeneity from extracts of sheep liver. In the past, various
      cofactors have been suggested for threonine dehydratase from both prokaryotic and
      eukaryotic tissue. While some direct evidence for the presence of pyriodoxal 5'
      phosphate in impure preparations is present in the literature no direct evidence
      for the cofactor in homogeneous dehydrogenase from mammalian tissue has been
      reported. The threonine dehydratase of sheep liver has been obtained in a
      homogeneous form and a spectral study provides clear evidence for the presence of
      pyridoxal 5'-phosphate. Both the physical properties of homogeneous threonine
      dehydratase and a study of spectral properties of its cofactor are reported in
      this communication.

PMID- 8251758
TI  - Purification and characterization of the recombinant 5 S subunit of
      transcarboxylase from Escherichia coli.
AB  - Transcarboxylase from Propionibacterium shermanii is a biotin-containing enzyme
      which catalyzes the reversible transfer of a carboxyl group from methylmalonyl
      CoA to pyruvate. It is composed of a central, hexameric 12 S subunit, 6 outer
      dimeric 5 S subunits which are held in a complex by 12 1.3 S biotinyl subunits.
      The transcarboxylase reaction requires two partial reactions, one of which is
      specific to 5 S. The cloning and expression of each of these subunits in
      Escherichia coli have been reported. We have designed a method for the
      purification of the 5 S subunit from an E. coli expression system. Protein
      purified to homogeneity by this method was shown to be active in the 5 S partial
      reaction, but unable to catalyze the overall transcarboxylase reaction. This
      protein was characterized as to its ability to form stable dimers, associate with
      the 1.3 S subunit in stable complexes referred to as 6 S, and assemble whole TC.
      The latter activity was shown to be lacking. The purified protein has a native
      molecular weight of 120 kDa and a subunit molecular weight of 60 kDa, consistent
      with the 5 S dimer. Plasma emission analysis of the metal content of the
      recombinant protein demonstrated the presence of both Co and Zn, comparable to
      the authentic protein. Fluorescence analysis verified the ability of the purified
      protein to bind substrates and 1.3 S subunits appropriately. Sequencing of the
      amino terminus and determination of the amino acid composition of the recombinant
      protein relative to that of the authentic subunit further verified the identity
      of the purified protein.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251759
TI  - Purification and characterization of Pseudomonas putida histidine ammonia-lyase
      expressed in Escherichia coli.
AB  - Histidine ammonia-lyase (HAL) from Pseudomonas putida PRS1 contains a
      catalytically important electrophilic center reported to be dehydroalanine.
      Little is known about the origin of this group or its linkage to the protein. To
      initiate structural studies on this enzyme, P. putida HAL was purified from an
      Escherichia coli high-expression clone in which the HAL gene (hutH) was under the
      control of the lambda PL promoter on a plasmid vector. In this clone from 6 to
      10% of the soluble cell protein after heat induction was HAL and approximately
      200 mg of 95% pure HAL could be obtained from 120 g wet weight of cells in a 40
      to 60% yield. The overexpressed protein was identical to P. putida HAL in native
      molecular weight (220 kDa), subunit composition (four identical subunits of 53
      kDa each), affinity for substrate (L-histidine Km of 5.3 mM at pH 9.0), and its
      sensitivity to inactivation by cyanide and bisulfite. The N-terminal amino acid
      sequence was in agreement with the DNA-predicted sequence, indicating proper
      translational initiation. These features make this enzyme an appropriate
      candidate for protein structure investigations regarding the nature of the
      electrophilic center and its association with the protein.

PMID- 8251760
TI  - Construction of an expression and site-directed mutagenesis system of haloalkane
      dehalogenase in Escherichia coli.
AB  - Haloalkane dehalogenase from Xanthobacter autotrophicus was efficiently expressed
      in Escherichia coli BL21 (DE3) and E. coli JM101. After introduction of
      restriction sites by PCR the haloalkane dehalogenase gene (dhlA) was
      translationally fused behind the T7 (phi 10), trc, and tac promoters. This
      resulted in expression at 30 degrees C up to 38 and 18% of the total soluble
      cellular protein with the T7 and trc promoters, respectively. Dehalogenase
      expression under control of the tac promoter was below 1% of the soluble cell
      protein, however. Aggregation of haloalkane dehalogenase into inclusion bodies
      was found during growth at 37 degrees C but not at 30 degrees C. Aggregates were
      also formed from intact enzyme upon incubation at 37 degrees C of cells or crude
      extracts containing active mature dehalogenase. The high level of expression
      resulted in a short purification procedure in which 30-35 mg highly enriched
      haloalkane dehalogenase was obtained from an 0.51 culture. For the production of
      single-stranded DNA an f1(+) origin was introduced in the T7 expression system.

PMID- 8251761
TI  - Human group II phospholipase A2 expressed in Trichoplusia ni larvae--isolation
      and kinetic properties of the enzyme.
AB  - Human secreted synovial fluid/platelet-type group II phospholipase A2 (sPLA2) was
      expressed in Trichoplusia ni (cabbage looper) larvae and cultured Sf9 insect
      cells by infection with a recombinant baculovirus. Active sPLA2, with correct N
      terminal proteolytic processing, was not secreted by Sf9 cells in culture. The
      enzyme was isolated from their homogenate without any need for refolding or
      renaturation of the protein. The enzyme was extracted from the 5000g pellet with
      1 M KBr and isolated by chromatography on a cation exchange column followed by
      reverse-phase chromatography on a Butyl Aquapore column. The yield of active
      enzyme (25 micrograms/g insect) was comparable to yields obtained in CHO cells or
      Escherichia coli by other investigators. The recombinant enzyme had the correct N
      terminal sequence, expected molecular weight, and reacted with antisera raised
      against peptides inferred from the cDNA sequence of the natural enzyme.
      Monoclonal antibodies were raised against the recombinant sPLA2 and they
      permitted the isolation of the natural enzyme from human serum by immunoaffinity.
      The recombinant sPLA2 showed a preference for substrate vesicles with a net
      negative charge. The baculovirus expression system provided active sPLA2 that can
      be produced economically in insects, purified simply, had well-defined kinetic
      properties, and should be useful in studies of inflammatory disorders.

PMID- 8251762
TI  - Escherichia coli: derived murine interleukin-1 beta with N-terminus partially N
      alpha-acetylated.
AB  - Two forms of murine recombinant interleukin-1 beta (mrIL-1 beta) from Escherichia
      coli were purified by ion exchange column chromatography; each exhibited
      equivalent biological activity in the murine thymocyte proliferation assay. It
      was determined by mass spectrometry of tryptic peptides that both retained the
      initiating methionine but one form was N alpha-acetylated at the N-terminus.

PMID- 8251763
TI  - Mitogenic action of insulin-like growth factor-I on human osteosarcoma MG-63
      cells and rat osteoblasts maintained in situ: the role of glucose-6-phosphate
      dehydrogenase.
AB  - The mechanisms involved in the mitogenic actions of insulin-like growth factor-I
      (IGF-I) on skeletal cells are at present unclear. We have investigated the role
      of glucose-6-phosphate dehydrogenase (G6PD) in this mechanism and provide strong
      evidence that stimulation of G6PD activity is required for the growth promoting
      activities of IGF-I. IGF-I (10 ng/ml) significantly elevated G6PD activity in MG
      63 human osteosarcoma cells within 30 min which preceded the IGF-I induced DNA
      synthesis in these cells. Inhibition of G6PD activity by epiandrosterone
      decreased DNA synthesis in IGF-I stimulated MG-63 cells but this was partly
      overcome by the addition of a combination of the four deoxyribonucleosides. IGF-I
      did not cause a general increase in cell metabolism as succinate dehydrogenase
      and iso-citrate dehydrogenase activity were not altered. Although IGF-I caused a
      significant increase in lactate dehydrogenase activity this was not inhibited by
      epiandrosterone. The culture of metatarsals of 4-week-old rats with IGF-I (10
      ng/ml) also stimulated G6PD activity in osteoblasts lining the metaphyseal
      trabeculae.

PMID- 8251764
TI  - Wolff's law: an 'MGS' derivation of Gamma in the Three-Way Rule for mechanically
      controlled lamellar bone modeling drifts.
AB  - The Gamma function in a model called the Three-Way Rule can predict qualitatively
      some responses of lamellar bone modeling drifts to defined longitudinal bone
      strain patterns. The derivation of Gamma in this article suggests a way to define
      it from in vivo longitudinal bond strain measurements. It depends on three
      operators called M, G and S. Let M equal +1 on any part of a bone surface (the
      'study surface') where the local Magnitude of the longitudinal mechanical strains
      exceeds a threshold that can turn adaptive modeling drifts ON; otherwise let it
      equal zero. For the cross section of a bone or trabecula that intersects the
      study surface, let G equal +1 when the Greatest strain over the whole cross
      section is in tension, but -1 if it is in compression. On a study surface where M
      = +1, let S equal G in uniaxial loading, but +1 if the Subsurface strain gradient
      emerging from inside the bone to this study surface is positive, and -1 if this
      gradient is negative. Then the product of M x G x S yields gamma as +1, 0 or -1,
      and those are its only permitted values. The values would mean a mechanically
      induced formation drift, or no drift, or a resorption drift, respectively should
      begin on that study surface. Gamma can predict the drift patterns in five basic
      or 'principal' structural adaptations of trabeculae, cortex and whole bones to
      defined mechanical challenges and bone strain patterns.

PMID- 8251765
TI  - Osteopontin mRNA expression during bone resorption: an in situ hybridization
      study of induced ectopic bone in the rat.
AB  - To study the relationship between the expression of osteopontin mRNA and ectopic
      bone formation and resorption, in situ hybridization using 35S-labeled RNA probes
      was performed on ectopic bone that was induced in an experimental rat model. The
      expression of type I collagen and osteocalcin in this ectopic bone was also
      examined. After 6-week-old male Wistar rats were injected intravenously with
      colchicine at a dose of 1 mg/kg, trabecular bone-like ectopic calcified tissue
      had formed in the medial bone marrow cavity of the tibia on day 4, and then
      continued to increase progressing forward to the distal cavity. On day 8 peak
      growth was attained, after which it was resorbed within 4 days as a result of
      osteoclast recruitment. Subsequent in situ hybridization of sections of the
      ectopic bone at 4, 6, 8, and 10 days after this colchicine treatment revealed
      that high levels of the type I collagen mRNA were expressed in the osteoblasts of
      the mineralized ectopic bone surface, not only during the formation period but
      also during bone resorption. Although osteocalcin showed no specific signals
      throughout the experiments, osteopontin mRNA was expressed temporarily at day 10
      during the initial phases of ectopic bone resorption, primarily in both
      osteoblasts and osteocytes and further in some osteoclasts. These results suggest
      that de novo synthesis of osteopontin is closely associated with bone resorption
      and could possibly be required to initiate and mediate this biological process.

PMID- 8251766
TI  - Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite
      formation and growth in a gelatin-gel.
AB  - Osteopontin is a phosphorylated bone matrix sialoprotein, postulated to play a
      regulatory role in biomineralization. The effects of a crude preparation of rat
      bone osteopontin and a more highly purified bovine bone osteopontin were
      evaluated using a gel diffusion system to measure effects of 0.1-100
      micrograms/ml of this matrix protein on hydroxyapatite formation and crystal
      proliferation. Bovine osteopontin at concentrations greater than 25 micrograms/ml
      inhibited both hydroxyapatite formation and growth in a dose-dependent manner.
      Osteopontin at concentrations lower than 25 micrograms/ml had no detectable
      effect on the amount of mineral accumulated in experiments with and without pre
      formed hydroxyapatite seed crystals either when initial mineral deposition was
      assessed at 3.5 days, or when mineral formation and growth were assessed at 5
      days. There was a statistically significant dose-dependent decrease in crystal
      length at all concentrations tested. The rat osteopontin preparation had similar
      inhibitory abilities. Partial dephosphorylation of bovine osteopontin with
      alkaline phosphatase removed its inhibitory ability, and reduced its ability to
      bind calcium. The affinity of bovine osteopontin for hydroxyapatite was
      determined based on a Langmuir adsorption isotherm, with values of K (binding
      affinity) and N (number of binding sites) being 0.026 ml/microgram and 1084
      micrograms/m2, respectively. The data suggest that, in this system, osteopontin
      is an effective inhibitor of hydroxyapatite formation and growth due to its
      affinity for the hydroxyapatite crystals. In this system, osteopontin, distinct
      from other phosphoproteins which both promote and inhibit hydroxyapatite
      deposition, did not enhance mineral formation at any concentration tested.

PMID- 8251767
TI  - Methylpentylaminopropylidenebisphosphonate (BM 21.0955): a new potent and safe
      bisphosphonate for the treatment of cancer-associated hypercalcemia.
AB  - Bisphosphonates have been shown to be effective in lowering serum calcium levels
      in patients with cancer-associated hypercalcemia. 1-Hydroxy-3
      (methylpentylamino)propylidenebisphosphonate (BM 21.0955) was developed as a
      third generation bisphosphonate and has been recently proven effective in animals
      and in patients with Paget's disease or tumor osteolysis. Thirty-six patients
      with cancer-associated hypercalcemia were treated with increasing doses (0.2-2.0
      mg) of BM 21.0955 by single i.v. infusion over 4 h in a phase I trial. Six
      patients were rejected from analysis due to concomitant treatment with other
      bisphosphonates or chemotherapy. After rehydration and infusion of BM 21.0955 the
      mean serum calcium levels fell significantly (P < 0.001), from 3.29 +/- 0.49
      mmol/l to 3.04 +/- 0.44 mmol/l until day 2 and normalized on day 6 (2.66 +/- 0.33
      mmol/l). Serum calcium was reduced in all patients and normalized in 16. No
      symptomatic hypocalcemia occurred. Mean serum creatinine decreased significantly
      (P < 0.01), from 1.25 +/- 0.58 mg/dl (day 0) to 1.05 +/- 0.37 mg/dl (day 6). The
      mean urinary calcium/creatinine concentration fell significantly (P < 0.001),
      from 1.90 +/- 1.16 mM/mM (day 0) to 0.37 +/- 0.34 mM/mM/l (day 6). There were no
      subjective drug-related side effects during or after the infusion. Thirteen
      patients had elevations of morning body temperature above 38 degrees C. This was
      due to confirmed infections in five patients and possibly drug- or tumor-related
      in the other eight. We conclude from these preliminary results that a single
      infusion of BM 21.0955 is an effective and safe way to treat cancer-associated
      hypercalcemia.

PMID- 8251768
TI  - Tamoxifen reduces bone turnover and prevents lumbar spine and proximal femoral
      bone loss in early postmenopausal women.
AB  - Although widely used for its anti-estrogen properties tamoxifen has estrogen like
      effects on a number of tissues including bone and liver. Previous studies suggest
      a preservation of lumbar spine density in postmenopausal women but the effect on
      the hip had not been addressed. To determine whether tamoxifen prevents bone loss
      in the early postmenopausal period bone mineral density at the lumbar spine and
      femoral neck was measured using dual energy X-ray absorptiometry at presentation
      and 6 monthly thereafter for 1 year in a prospective controlled study. Also
      indices of bone turnover, serum osteocalcin and urinary hydroxyproline excretion,
      were assessed. Fifteen early postmenopausal women with Stage I or II breast
      cancer treated with tamoxifen and 21 normal postmenopausal women were studied.
      Sex hormone binding globulin and antithrombin III levels in serum were also
      measured as indices of the hepatic estrogenic activity. Tamoxifen (20 mg daily)
      prevented bone loss at the femoral neck and lumbar spine. Median rates of change
      in bone mineral density (%/year) for the tamoxifen group were +0.09%/year in the
      lumbar spine and 1.4%/year in the femoral neck compared with -2.3%/year and 
      1.8%/year for the control group (P = 0.04 and 0.03, respectively). Tamoxifen
      resulted in a significant decrease in both serum osteocalcin and urinary
      hydroxyproline by 6 months of treatment and this effect persisted for the 12
      months of observation. An increase in sex hormone binding globulin and a decline
      in antithrombin III levels was also observed. These data indicate that, in
      recently, postmenopausal women tamoxifen prevented bone loss at both the lumbar
      spine and femur and reduced bone turnover.

PMID- 8251769
TI  - In vitro evaluation of dose-effects of ethanol on human osteoblastic cells.
AB  - Chronic alcoholism represents a high risk for fractures and osteopenia. Previous
      histomorphometric studies reported a decreased bone formation, but it has never
      been established whether ethanol has a direct toxic effect on osteoblasts. This
      present in vitro study was performed on human osteoblast cells derived from bone
      explants after collagenase digestion. The direct effect of ethanol was determined
      after 4 days of exposure to various doses, ranging from 0.01 to 5 g/l on the
      alkaline phosphatase (AP) activity, osteocalcin secretion and [3H]thymidine
      incorporation. The influence of the duration of exposure to 0.8 g/l ethanol was
      also determined. A significant and dose-dependent decrease in the cell
      proliferation was observed. AP activity was significantly decreased by high doses
      of ethanol (2-5 g/l). A biphasic effect of ethanol was noted on osteocalcin
      secretion according to the dose: it decreased at doses lower than 0.8 g/l and
      increased at the highest concentrations. At the dose of 0.8 g/l, whatever the
      duration of exposure, the decrease of the proliferation was of the same magnitude
      and no significant change in AP activity was observed. Significant ethanol
      induced effects on osteocalcin secretion were observed only after 4 and 8 days of
      exposure. These data demonstrate that ethanol may have a direct toxic effect on
      osteoblast activity and proliferation. This could be one of the mechanisms of
      alcohol-induced osteopenia which has a multifactorial pathophysiology.

PMID- 8251770
TI  - Can we afford the welfare state?

PMID- 8251771
TI  - Atopy and its inheritance.

PMID- 8251772
TI  - Deaths from stroke in younger people.

PMID- 8251773
TI  - A model for British medical education.

PMID- 8251774
TI  - Is an eye pad needed in cases of corneal abrasion?

PMID- 8251775
TI  - AIDS row closes German health office.

PMID- 8251776
TI  - Local confidential inquiry into avoidable factors in deaths from stroke and
      hypertensive disease.
AB  - OBJECTIVE: To audit avoidable deaths from stroke and hypertensive disease.
      DESIGN: Details of care before death were obtained from general practitioners and
      other doctors, anonymised, and assessed by two experts against agreed minimum
      standards of good practice for detecting and managing hypertension. SETTING:
      Health authority with population of 250,000. SUBJECTS: All patients under 75
      years who died of stroke, hypertensive disease, or hypertension related causes
      during November 1990 to October 1991. MAIN OUTCOME MEASURES: Presence of
      important avoidable factors and departures from minimum standards of good
      practice. RESULTS: Adequate information was obtained for 88% (123/139) of
      eligible cases. Agreement between the assessors was mostly satisfactory. 29%
      (36/123, 95% confidence interval 21% to 37%) of all cases and 44% (36/81, 34% to
      55%) of those with definite hypertension had avoidable factors that may have
      contributed to death. These were most commonly failures of follow up and
      continuing smoking. Assessment against standards of minimum good practice showed
      that care was inadequate but not necessarily deemed to have contributed to death,
      in a large proportion of patients with definite hypertension. Common shortcomings
      were inadequate follow up, clinical investigation, and recording of smoking and
      other relevant risk behaviours. CONCLUSIONS: This method of audit can identify
      shortcomings in care of patients dying of hypertension related disease.

PMID- 8251777
TI  - Second malignant neoplasms after cancer in childhood or adolescence. Nordic
      Society of Paediatric Haematology and Oncology Association of the Nordic Cancer
      Registries.
AB  - OBJECTIVE: To assess the relative risk of developing a second malignant neoplasm
      in people with a diagnosis of cancer in childhood and adolescence. DESIGN:
      Register based follow up study. SETTING: Populations of Nordic countries.
      SUBJECTS: 30,880 people under the age of 20 with a first malignant neoplasm
      diagnosed during the period 1943-87. MAIN OUTCOME MEASURES: Relative and
      attributable risks of second malignant neoplasms by type of first cancer, age at
      first diagnosis, calendar period, sex, and country. Expected figures were based
      on the appropriate national incidence rates for cancer. RESULTS: 247 cases of
      second malignant neoplasms were observed in 238 patients, yielding a relative
      risk for cancer of 3.6 (95% confidence interval 3.1 to 4.1). The risk changed
      significantly from 2.6 in people first diagnosed during the 1940s and 1950s to
      6.9 among cohort members included in the late 1970s and 1980s. Increases were
      observed for most types of cancer. Highest levels of the relative risk were seen
      during the 10 years immediately after first malignant diagnosis. The incidence of
      second malignant neoplasms attributable to the first cancer and associated
      treatments, however, showed a consistent rise throughout the 45 years of follow
      up. CONCLUSION: The estimated risks for a second malignant neoplasm were
      significantly lower than those found in most large hospital based studies but
      compatible with the results from a similar population based study in the United
      Kingdom. Extent of risk and cancer pattern were similar among the Nordic
      countries and are believed to be representative for a large part of the European
      population.

PMID- 8251778
TI  - Treatment of filarial lymphoedema and elephantiasis with 5,6-benzo-alpha-pyrone
      (coumarin).
AB  - OBJECTIVE: To study efficacy of treatment of filarial lymphoedema and
      elephantiasis with 5,6-benzo-alpha-pyrone. DESIGN: Randomised, double blind,
      placebo controlled study with matching for grade and duration of disease, age,
      and sex. Treatment was given for 367 days, and subjects were followed up for
      another year. SETTING: A town in Shandong Province, China. SUBJECTS: 104 men and
      women with chronic unilateral filarial lymphoedema or elephantiasis of the leg:
      64 were randomised to benzopyrone and 40 to placebo. By the end of the study 19
      patients had dropped out of the treatment group and two out of the placebo group.
      INTERVENTIONS: Two 200 mg tablets of 5,6-benzo-alpha-pyrone or two placebo
      tablets given daily. MAIN OUTCOME MEASURES: Volumes of the affected and normal
      legs estimated every three months, and daily listing of any side effects.
      RESULTS: Benzopyrone reduced oedema for all grades of lymphoedema during the year
      of treatment (pW0.001) and the follow up year (p = 0.026). During treatment the
      mean monthly reductions in leg volume were 0.62% (95% confidence intervals 0.4%
      to 0.85%), 1.1% (0.71% to 1.6%), and 1.6% (0.89% to 2.3%) of the volume of the
      normal leg for grades 1, 2, and 3-5 (elephantiasis) of lymphoedema respectively.
      During follow up the mean monthly reductions were 0.18% (0.01% to 0.35%), 0.54%
      (0.27% to 0.82%), and 0.87% (0.51% to 1.2%). At the end of the trial the total
      reduction in oedema was 100%, 95%, and 45% for grades 1, 2, and 3-5. Symptoms and
      complications were considerably reduced, including attacks of secondary acute
      inflammation, while side effects were minor and disappeared after one month. In
      the placebo group there were no changes in the severity of lymphoedema.
      CONCLUSIONS: 5,6-benzo-alpha-pyrone reduces the oedema and many symptoms of
      filarial lymphoedema and elephantiasis. It has few side effects, and its
      relatively slow action makes it ideal for use without compression garments.

PMID- 8251779
TI  - Use of structured letters to improve communication between hospital doctors and
      general practitioners.

PMID- 8251780
TI  - Diabetes registers: a grassroots approach.
AB  - OBJECTIVES: To compile a register of diabetic patients within the catchment area
      of a district general hospital and evaluate the characteristics of the population
      using aggregated data from a general practice audit. DESIGN: Cross sectional
      study. Practices identified all known diabetics and completed a questionnaire
      from information in each patient's medical record. SETTING: Practices affiliated
      to a district audit group in south east England. MAIN OUTCOME MEASURES: Number of
      participating practices; prevalence of diabetes and its complications; and sex
      distribution of patients, age at diagnosis and review, treatment, and metabolic
      control. Comparisons with similar data from other studies. RESULTS: 41 out of 43
      practices participated, and 2574 diabetic patients were identified (prevalence
      1.18%). 52.4% of patients were male. The mean age was 61.6 years. 32% of patients
      were treated with insulin, 51.5% with oral hypoglycaemic agents, 16.5% with diet
      alone. The mean random blood glucose concentration was 10.4 mmol/l and
      glycosylated haemoglobin 10.1%. 8% had proteinuria, 7% a history of myocardial
      infarction, 5% a history of stroke, and 2% a diabetes related amputation. These
      proportions were not significantly different from those found in studies
      performed by different methods in Poole, Islington, Powys, Trowbridge, and
      Southall. CONCLUSION: It is feasible to compile a register of diabetic patients
      in a district and evaluate their characteristics by using only general practice
      sources.

PMID- 8251781
TI  - Diagnosis and management of methicillin resistant Staphylococcus aureus
      infection.

PMID- 8251782
TI  - Tuberculous pericarditis with rapid progression to constriction. Prompt diagnosis
      and treatment are needed.

PMID- 8251783
TI  - Science or flat earthers? The clinical ecologist replies.

PMID- 8251784
TI  - Severe lactic acidosis in patient receiving continuous ambulatory peritoneal
      dialysis.

PMID- 8251785
TI  - "Postretirement polydipsia" mimicking prostatism.

PMID- 8251786
TI  - ABC of emergency radiology. The elbow.

PMID- 8251787
TI  - Rituals in antenatal care. Consider women's psychosocial needs.

PMID- 8251788
TI  - Rituals in antenatal care. Women should understand the need for change.

PMID- 8251789
TI  - Routine ultrasound scanning in pregnancy.

PMID- 8251790
TI  - Routine postnatal examination. Pelvimetry is unnecessary ...

PMID- 8251791
TI  - Assessment of elderly people in hospital. Use clinically relevant assessment
      tool.

PMID- 8251792
TI  - Assessing people's ability to drive after stroke.

PMID- 8251793
TI  - Iron and coronary heart disease. Iron makes myocardium vulnerable to ischemia.

PMID- 8251794
TI  - Iron and coronary heart disease. Control for haematological variables.

PMID- 8251795
TI  - Iron and coronary heart disease. Iron linked to immune activation.

PMID- 8251796
TI  - Psychotherapy. Is wanted, needed, and valued in the NHS.

PMID- 8251797
TI  - Treatment at Broadmoor Hospital.

PMID- 8251798
TI  - Psychotherapy. Short term therapies not always adequate.

PMID- 8251799
TI  - New weightings for analysing prescribing in general practice.

PMID- 8251800
TI  - Socioeconomic differentials in wealth and health.

PMID- 8251801
TI  - Childhood drownings: who is responsible?

PMID- 8251802
TI  - Maternal "near miss" reports?

PMID- 8251803
TI  - Giftedness. Parents and schools should provide for gifted children.

PMID- 8251804
TI  - The latest reorganisation of the NHS.

PMID- 8251805
TI  - Effect of concurrent acute infection with hepatitis C virus on acute hepatitis B
      virus infection.
AB  - OBJECTIVE: To investigate the possible interference with acute hepatitis B virus
      infection by co-infection with hepatitis C virus. DESIGN: Analysis of stored sera
      collected for transfusion transmitted viruses study in 1970s. SETTING: Four major
      medical centres in the United States. PATIENTS: 12 recipients of blood infected
      with hepatitis B virus. MAIN OUTCOME MEASURES: In 1970s, presence of antibodies
      in hepatitis B virus and raised serum alanine aminotransferase concentration;
      detection of antibodies to hepatitis C virus with new enzyme linked immunoassays.
      RESULTS: Five of the 12 patients were coinfected with hepatitis C virus.
      Hepatitis B surface antigen was first detected at day 59 in patients infected
      with hepatitis B virus alone and at day 97 in those coinfected with hepatitis C
      virus (p = 0.01); median durations of antigenaemia were 83 and 21 days
      respectively (p = 0.05), and the antigen concentration was lower in the
      coinfected patients. Alanine aminotransferase patterns were uniphasic when
      hepatitis B virus infection occurred alone (range 479-2465 IU/l) and biphasic in
      patients with combined acute infection (no value > 380 IU/l; p = 0.0025). Four
      coinfected recipients developed chronic hepatitis C virus infection. The fifth
      patient was followed for only four months. CONCLUSIONS: Acute coinfection with
      hepatitis C virus and hepatitis B virus inhibits hepatitis B virus infection in
      humans, and onset of hepatitis B may reduce the severity of hepatitis C virus
      infection but not frequency of chronicity. Alanine aminotransferase concentration
      showed a biphasic pattern in dual infection.

PMID- 8251806
TI  - Social deprivation and premature mortality: regional comparison across England.
AB  - OBJECTIVE: To investigate the pattern and size of the relationship between social
      deprivation in electoral wards and premature mortality for each health region in
      England. DESIGN: Ecological study using 1981 census variables and data on
      mortality for 1981-5. SETTING: 14 regional health authorities in England. MAIN
      OUTCOME MEASURE: Mortality under the age of 65 years from all causes, coronary
      heart disease, and smoking related diseases in men and women. RESULTS: Increasing
      deprivation was significantly associated with mortality from all causes, coronary
      heart disease, and smoking related diseases. The relationship was linear with no
      apparent threshold. Correlation coefficients were generally greater for deaths
      from all causes and smoking related diseases and for men compared with women. The
      slope of the relationship between deprivation and mortality varied among regions.
      Variations in mortality still existed between regions for equal levels of
      deprivation. CONCLUSION: Deprivation of an area and premature mortality are
      strongly linked. The effects of deprivation can be seen throughout the range of
      affluence and are not limited to the poorest areas. Current targets for reducing
      coronary heart disease mortality may be achievable if the mortality in poor areas
      can be reduced to the rates in affluent areas.

PMID- 8251807
TI  - Stressful life events, social support, and mortality in men born in 1933.
AB  - OBJECTIVE: To examine relations between stressful life events and mortality in
      middle aged men. DESIGN: Prospective population study. Data on stressful life
      events, social network, occupation, and other psychosocial factors derived from
      self administered questionnaires. Mortality data obtained from official
      registers. SETTING: City of Gothenburg, Sweden. SUBJECTS: 752 men from a random
      population sample of 1016 men aged 50. MAIN OUTCOME MEASURE: Mortality from all
      causes during seven years' follow up. RESULTS: Life events which had occurred in
      the year before the baseline examination were significantly associated with
      mortality from all causes during seven years' follow up. Of the men who had
      experienced three or more events during the past year 10.9% had died compared
      with 3.3% among those with no life events (odds ratio 3.6; 95% confidence
      interval 1.5 to 8.5). The association between recent life events and mortality
      remained true after smoking, self perceived health, occupational class, and
      indices of social support were controlled for. Many of the deaths were alcohol
      related, but the number of deaths was too small to allow for analyses of specific
      causes of death. The association between life events and mortality was evident
      only in men with low emotional support. CONCLUSION: Stressful life events are
      associated with high mortality in middle aged men. Men with adequate emotional
      support seem to be protected.

PMID- 8251808
TI  - A randomised controlled trial to test equivalence between retinyl palmitate and
      beta carotene for vitamin A deficiency.
AB  - OBJECTIVES: To determine whether beta carotene is therapeutically equivalent to
      retinyl palmitate in the formulation currently recommended by the World Health
      Organisation. DESIGN: Randomised blind equivalence trial. SETTING: Rural area in
      Senegal. SUBJECTS: Children aged 2-15 years suffering from vitamin A deficiency
      as defined by abnormal results on eye cytology were randomly allocated treatment
      with retinyl palmitate (n = 256) and beta carotene (n = 254). MAIN OUTCOME
      MEASURE: Reversion to normal results on eye cytology as defined by the
      reappearance of goblet cells and normalisation of the epithelial cells. RESULTS:
      Seven weeks after the supplement was given the percentages were 51.2% (124/242)
      children taking retinyl palmitate and 50.0% (123/246) of those taking beta
      carotene, who had reverted to normal eye cytology, a difference of 1.2% (95%
      confidence interval 6.2% to 8.6%) [corrected]. According to an equivalence
      testing procedure, the two treatments were statistically equivalent; the null
      hypothesis of non-equivalence was rejected (one tailed p value = 0.03).
      CONCLUSIONS: beta Carotene supplementation seems to be a promising candidate for
      the alleviation of vitamin A deficiency. It could be given either as high dose
      capsule or through increased dietary intake. The challenge now is to improve
      dietary intake of vitamin A in programmes that are effective and sustainable at
      the community level.

PMID- 8251810
TI  - Influence of social deprivation on illness in diabetic patients.

PMID- 8251809
TI  - Prediction of osteoporotic fractures by postural instability and bone density.
AB  - OBJECTIVE: To investigate the utility of risk factors such as bone mineral
      density, lifestyle, and postural stability in the prediction of osteoporotic
      fractures. DESIGN: Longitudinal, epidemiological, and population based survey.
      SETTING: City of Dubbo, New South Wales. SUBJECTS: All residents of Dubbo aged >
      or = 60 on 1 January 1989. MAIN OUTCOME MEASURE: Incidence of fracture for
      individual subjects. RESULTS: The overall incidence of atraumatic fractures in
      men and women was 1.9% and 3.1% per annum respectively. The predominant sites of
      fracture were hip (18.9%), distal radius (18.5%), ribs and humerus (11.9% in each
      case), and ankle and foot (9.1% and 6.6% respectively). Major predictors of
      fractures in men and women were femoral neck bone mineral density, body sway, and
      quadriceps strength. Age, years since menopause, height, weight, and lifestyle
      factors were also correlated with bone mineral density and body sway and hence
      were indirect risk factors for fracture. Discriminant function analysis correctly
      identified 96% and 93% (sensitivities 88% and 81%) of men and women,
      respectively, who subsequently developed atraumatic fractures. Predictions based
      on this model indicated that a woman with a bone mineral density in the lowest
      quartile in the hip together with high body sway had a 8.4% probability of
      fracture per annum. This represented an almost 14-fold increase in risk of
      fracture compared with a woman in the highest bone mineral density quartile with
      low postural sway. An individual with all three predictors in the "highest risk"
      quartile had a 13.1% risk of fracture per annum. CONCLUSIONS: Bone mineral
      density, body sway, and muscle strength are independent and powerful synergistic
      predictors of fracture incidence.

PMID- 8251811
TI  - Childless women revisited. South Bedfordshire Practitioners' Group.

PMID- 8251812
TI  - Value of radiological follow up of childhood pneumonia.

PMID- 8251813
TI  - Capitation funding: population, age, and mortality adjustments for regional and
      district health authorities in England.
AB  - OBJECTIVE: To assess the effect of each of the components of the national
      capitation funding formula--population projections and age and mortality
      weighting--at regional and district level. DESIGN: Application of age-cost and
      mortality weights to the projected 1997 populations of regions and districts,
      based on the Department of Health public health common dataset. SETTING: Regional
      and district health authorities in England. RESULTS: The application of the age
      cost and mortality weights to projected populations resulted in greater changes
      in the shares of weighted populations relative to the estimated 1991 population
      at district level (mean 0, range -17% to 28%) than at regional level (mean 0,
      range -9% to 6%). At district level mortality weights had less scope for
      influence (mean 0, range -9% to 14%) than population projections (mean 0, range 
      16% to 31%) or age weights (mean 0, range -20% to 30%). CONCLUSIONS: The
      adjustments to the 1991 population shares due to the application of the national
      capitation funding formula depend on the interaction of three elements: the
      projected population by age group, the age-cost weight, and the mortality weight.
      Since each is open to uncertainty, either in terms of measurement (projected
      population, particularly for births and the over 85s) or method (derivation of
      the age-cost and mortality weights), the formula should be implemented cautiously
      at district level. Ways should be considered of incorporating elements of
      uncertainty into the model. Further research is required on the elements and
      degree of uncertainty in each of these components, as well as on the relative
      health needs of different populations.

PMID- 8251814
TI  - Diabetes and rhabdomyolysis. A rare complication of a common disease.

PMID- 8251815
TI  - ABC of emergency radiology. The shoulder.

PMID- 8251816
TI  - Collapsing health care in Serbia and Montenegro.
AB  - Serbia and Montenegro together form the Federal Republic of Yugoslavia. As well
      as the Serb majority this includes the mixed province of Vojvodina, the mainly
      Albanian population in Kosovo, and the large Muslim minority in Sandzak. Since
      the start of war in 1991 the attention and sympathies of the world have focused
      on Bosnia and Croatia. The United Nations imposed economic sanctions on the
      federal republic in 1992, although in theory medical supplies and aid are exempt.
      The economy has now collapsed under the triple burden of war, loss of trade
      between the republics, and UN sanctions. A major public health catastrophe is
      unfolding in the federal republic.

PMID- 8251817
TI  - Vitamin K and childhood cancer.

PMID- 8251818
TI  - Caution over journal supplements.

PMID- 8251819
TI  - Surgical castration for sex offenders. An unlikely option.

PMID- 8251820
TI  - Surgical castration for sex offenders. Boundaries between surgery and mutilation
      are blurred.

PMID- 8251821
TI  - Urinary tract infection in childhood. Referral inconsistent.

PMID- 8251822
TI  - Giving intravenous drugs. Students should be trained and tested.

PMID- 8251823
TI  - Urinary tract infection in childhood. Dipstick testing a useful screening tool.

PMID- 8251824
TI  - Giving intravenous drugs. Prepared drugs save time.

PMID- 8251825
TI  - Deregulating emergency contraception. Counseling and education may suffer.

PMID- 8251826
TI  - Deregulating emergency contraception. Service should reflect greater demand after
      the weekend.

PMID- 8251827
TI  - Deregulating emergency contraception. Genitourinary clinics offer out of hours
      service.

PMID- 8251828
TI  - Primary care and public health. Differing roles create tension.

PMID- 8251829
TI  - Guidelines on sensible drinking are invaluable.

PMID- 8251830
TI  - Recommended dose of anti-D immunoglobulin.

PMID- 8251831
TI  - Deciding who should have thrombolysis.

PMID- 8251832
TI  - Smoking and benign breast cancer. Smoking linked to duct ectasia ...

PMID- 8251833
TI  - Smoking and benign breast cancer ... or is it?

PMID- 8251834
TI  - Failure of the new deal on juniors' hours.

PMID- 8251835
TI  - GPs' role and recognition. GPs taken for granted ...

PMID- 8251836
TI  - The Gardner hypothesis.

PMID- 8251837
TI  - General practitioners and incentives.

PMID- 8251838
TI  - Confidentiality, contraception, and young people.

PMID- 8251839
TI  - Junior doctors and the EC draft directive on working hours.

PMID- 8251840
TI  - Salt and asthma.

PMID- 8251841
TI  - New powers of supervised discharge of mentally ill people.

PMID- 8251842
TI  - Randomised controlled trial of oxytocin alone versus oxytocin and ergometrine in
      active management of third stage of labour.
AB  - OBJECTIVE: To compare intramuscular oxytocin alone and intramuscular oxytocin
      with ergometrine (Syntometrine) for their effect in reducing the risk of
      postpartum haemorrhage when both are used as part of the active management of the
      third stage of labour. DESIGN: Double blind, randomised controlled trial.
      SETTING: Two metropolitan teaching hospitals in Perth, Western Australia.
      SUBJECTS: All women who expected a vaginal birth during the period of the trial.
      Informed consent was obtained. MAIN OUTCOME MEASURES: Postpartum haemorrhage,
      nausea, vomiting, and increased blood pressure. RESULTS: 3497 women were randomly
      allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753).
      Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in
      both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to
      1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was
      associated with nausea, vomiting, and increased blood pressure. CONCLUSIONS:
      There are few advantages but several disadvantages for the routine use of
      oxytoxinergometrine when prophylactic active management of the third stage of
      labour is practised. Further investigation of dose-response for oxytocin may be
      warranted.

PMID- 8251843
TI  - Preregistration house officers in the Thames regions: changes in quality of
      training after four years.
AB  - OBJECTIVE: To measure changes in the training and workload of preregistration
      house officers over four years. DESIGN: Postal questionnaire. SETTING: The Thames
      health regions. PARTICIPANTS: 1049 preregistration house officers. RESULTS:
      Response rate was 69% (725 replies). The proportion of house officers officially
      on duty > 83 hours a week fell from at least 42% to 21%, and the proportion
      officially on duty < or = 72 hours rose from no more than 9% to 40%. Adequate
      guidance in breaking bad news increased from 25% to 46% (p < 0.0001; 95%
      confidence interval for difference, 16.2% to 25.8%) and guidance in pain control
      increased from 36% to 46% (p < 0.01; 5.0% to 15.0%). The number of house officers
      attending an induction course increased from 61% to 94% (p < 0.001; 28.9% to
      37.1%). There was no change in the proportion unable to attend formal educational
      sessions because of clinical commitments or in levels of satisfaction with
      consultants' educational supervision. The median number of inpatients under house
      officers' care fell from 20 to 17, but the numbers of patients clerked in an
      average week showed little change. House officers were less satisfied with the
      clinical experience their post provided (proportion dissatisfied rose from 30% to
      39%; p < 0.01; 4.2% to 13.8%) and less enthusiastic about recommending their post
      to a friend (proportion neutral or not recommending rose from 30% to 42%, p <
      0.0001; 7.9% to 16.9%). CONCLUSION: Despite progress in reducing hours of duty
      and providing induction courses, the training that hospitals and consultants
      provide for house officers is still unsatisfactory and inconsistent with the
      General Medical Council's recommendations.

PMID- 8251844
TI  - Preregistration house officers in eight English regions: survey of quality of
      training.
AB  - OBJECTIVE: To assess the quality of preregistration house officer training in
      eight English regions. DESIGN: Postal questionnaire. SETTING: Thames, East
      Anglian, Mersey, Northern, and Wessex regions. PARTICIPANTS: 1670 preregistration
      house officers. MAIN OUTCOME MEASURES: Education, hours of work, workload,
      conditions of work, and attitudes to job and medicine as a career. RESULTS:
      Response rate was 69% (1146 replies). Most house officers had attended induction
      courses (1036/1129 (92%)); 74% (757/1024) found them satisfactory. The
      proportions who had never received adequate guidance on how to break bad news and
      how to control pain were 59% (670/1135) and 56% (634/1136) respectively. There
      was much variation between regions. Overall, 65% (736/1138) reported confidence
      in performing cardiopulmonary resuscitation. Most respondents (95% (1089/1142))
      worked an on call rota, 3% (36) a partial shift, and 0.6% (seven) a full shift;
      19% (202) were on duty for average weekly hours that exceeded the targets for 1
      April 1993. House officers had a median of 20 patients under their care and
      clerked a median of 10 emergency cases, six routine cases, and two day cases a
      week. Over half (690/1128 (61%)) could not obtain hot food after 8 pm, 20%
      (223/1095) did not always have clean sheets available in their on call room, and
      45% (462/1036) did not consider the protection of staff against violence to be
      adequate at their hospital. The most important problems with the preregistration
      year were inappropriate or non-medical tasks (ranked first by 360 respondents),
      hours of work (359), and pay for out of hours work (167). Overall 57% (646/1125)
      would encourage a friend to apply for their post, but only 24% (266/1112) would
      encourage a friend to take up medicine and 44% (494/1112) would discourage the
      idea. CONCLUSIONS: House officers' training is deficient in important respects,
      with inappropriate tasks and heavy clinical workloads impeding the provision of
      proper education.

PMID- 8251845
TI  - Heterosexual transmission of HIV in injecting drug users.

PMID- 8251846
TI  - Postmarketing study of cardiovascular adverse reactions associated with
      sumatriptan.

PMID- 8251847
TI  - Effect of fundholding and indicative prescribing schemes on general
      practitioners' prescribing costs.
AB  - OBJECTIVE: To compare general practitioners' prescribing costs in fundholding and
      non-fundholding practices before and after implementation of the NHS reforms in
      April 1991. DESIGN: Analysis of prescribing and cost information (PACT data;
      levels 2 and 3) over two six month periods in 1991 and 1992. SETTING: Oxford
      region. PARTICIPANTS: Three dispensing fundholding practices; five non-dispensing
      fundholding practices; and seven non-dispensing, non-fundholding practices. MAIN
      OUTCOME MEASURES: Percentage change in net cost of ingredients, number of items
      prescribed, average cost per item, and proportion of generic drugs prescribed
      after NHS reforms. RESULTS: Prescribing costs increased in all practices in the
      six months after the reforms. The net costs of ingredients increased among
      dispensing fundholders by 10.2%, among non-dispensing fundholders by 13.2%, and
      among non-fundholders by 18.7%. The number of items prescribed also increased in
      all three groups (by 5.2%, 7.5%, and 6.1% respectively). The increase in average
      cost per item was 4.8% for dispensing fundholders, 5.3% for non-dispensing
      fundholders, and 11.9% for non-fundholders. Dispensing fundholders increased the
      proportion of generic drugs prescribed from 26.9% to 34.5% and non-dispensing
      fundholders from 44.5% to 48.7%; non-fundholders showed no change (47%). Five of
      the eight fundholding practices made savings in their drugs budgets at the end of
      the first year of fundholding (range 2.9-10.7%; the three other practices
      overspent by up to 3.6%). All non-fundholding practices exceeded their indicative
      prescribing amounts (range 3.2-20.0%). CONCLUSIONS: Fundholding has helped to
      curb increases in prescribing costs, even among dispensing general practitioners,
      for whom the incentives are different. Indicative prescribing amounts for non
      fundholding practices do not seem to have had the same effect.

PMID- 8251849
TI  - Patients' perception of their asthma. Accuracy of perception still unclear.

PMID- 8251848
TI  - Diabetic retinopathy.

PMID- 8251850
TI  - Patient's perception of their asthma. Children also misinterpret the signs.

PMID- 8251851
TI  - Surgical training. Training is inconsistent.

PMID- 8251852
TI  - Antibiotic prophylaxis in dental practice.

PMID- 8251853
TI  - Major incident planning.

PMID- 8251854
TI  - Prenatal screening for Down's Syndrome.

PMID- 8251855
TI  - Locum doctors. All systems for regulation are fallible.

PMID- 8251856
TI  - Locum doctors. Are undervalued.

PMID- 8251857
TI  - Transmission of infectious diseases in prison.

PMID- 8251858
TI  - Death from occupational disease.

PMID- 8251859
TI  - Adult moyamoya disease.

PMID- 8251860
TI  - Community supervision orders.

PMID- 8251861
TI  - Influenza immunization in elderly people.

PMID- 8251862
TI  - Deregulating emergency contraception.

PMID- 8251863
TI  - Paternal exposure to chemicals before conception.

PMID- 8251864
TI  - Value of measuring blood pressure in pregnancy.

PMID- 8251865
TI  - Unifying academic general practice. Preserve the practical approach.

PMID- 8251866
TI  - Unifying academic general practice. Trainers and tutors should get together.

PMID- 8251867
TI  - Time for community change: what has outreach to offer?

PMID- 8251868
TI  - The effect of implementation of non-smoking policies in the workplace: an update
      on the law.

PMID- 8251869
TI  - Adverse consequences of lysergic acid diethylamide.
AB  - The continued endemic use of hallucinogenic drugs, and of LSD in particular,
      raises concern regarding their short and long term adverse consequences. The
      epidemiology of LSD abuse is reviewed suggesting an increase in LSD use among the
      young as the prevalence rates for other substances continues to fall. Evidence
      supports the association of LSD use with panic reactions, prolonged
      schizoaffective psychoses and post-hallucinogen perceptual disorder, the latter
      being present continually for as long as 5 years. Evidence does not support
      claims of genetic disorders arising from hallucinogens. In light of the
      foregoing, current data confirm earlier findings of long lasting psychopathology
      arising in vulnerable individuals from the use of LSD. A hypothetical long term
      molecular mechanism of adverse effects is proposed.

PMID- 8251870
TI  - Measurement of the severity of amphetamine dependence.
AB  - A Severity of Amphetamine Dependence Questionnaire (SAmDQ) was administered to
      101 subjects attending an Australian drug dependency treatment centre. The SAmDQ
      was adapted from the Severity of Opiate and Alcohol Dependence Questionnaires
      (SODQ & SADQ). The structural characteristics of the SAmDQ were examined and
      compared with previous findings reported on samples of opiate addicts with the
      SODQ. A high degree of consistency was found between the results obtained with
      the SAmDQ and previous findings with the SODQ. The relationship between the SAmDQ
      and the Severity of Dependence Scale (SDS) was also examined. The findings
      suggest that further development of amphetamine dependence measurement is
      required.

PMID- 8251871
TI  - Consumption of buprenorphine and other drugs among heroin addicts under
      ambulatory treatment: results from cross-sectional studies in 1988 and 1990.
AB  - We assessed the prevalence of consumption of buprenorphine and other drugs among
      heroin addicts under ambulatory treatment in two cross-sectional studies
      conducted in 1988 (188 subjects) and in 1990 (197 subjects). Patients were
      enrolled in one of three different programmes: methadone maintenance programme
      (MMP), antagonist maintenance programme (AMP) and drug-free programme (DFP).
      Information given by participants was compared with results of urine screening
      for drugs. Urine samples were tested using enzyme immunoassay for the detection
      of heroin, cocaine, dextropropoxyphene, cannabis and benzodiazepines, and
      radioimmunoassay for buprenorphine. Sixty-six percent of patients in 1988 and 71%
      of patients in 1990 reported having consumed buprenorphine at some time during
      their history of drug dependence (period prevalence) and 5.9% and 6.1%,
      respectively, tested positive to the drug (point prevalence). In over 70% of
      these patients consumption was by the intravenous route. Consumption of cannabis,
      cocaine and benzodiazepines was also very high in the study population. Overall,
      patients in the DFP group consumed the largest number of the drugs tested, while
      those in the AMP group consumed the smallest number. Abuse of buprenorphine could
      be more widespread than previously reported.

PMID- 8251872
TI  - HIV risk among women injecting drug users who are in jail.
AB  - Female offender populations and females in jail include large proportions of
      injecting drug users (IDUs), who are at high risk of contracting or transmitting
      HIV. Women IDUs (n = 165) were recruited and interviewed at New York City's
      central jail facility for women. The study examined these women's patterns of HIV
      risk behaviors related to drugs and sex and identified behavioral and attitudinal
      correlates of HIV serostatus. The women typically used both injectable and non
      injectable drugs prior to arrest, primarily heroin, cocaine powder, crack, and
      illicit methadone. Self-reported HIV seropositivity was 43%. Variables correlated
      with HIV serostatus in the bivariate analysis were: cocaine injection frequency;
      lifetime injection risk behavior; providing oral sex during male crack use;
      Hispanic ethnicity; sharing of needles/syringes; sharing of cookers; sharing
      injection equipment with friends; heroin smoking (negative); injection risk
      acceptance; peer norms and behavior; lifetime sexual risk behavior; frequency of
      sex with men; provision of sex for money or drugs; and knowing people with AIDS.
      The first four variables listed retained statistical significance in a multiple
      logistic regression analysis. The paper considers the need to tailor AIDS
      prevention interventions for woman IDUs in jail, including taking into account
      risk behaviors that occur within frequently reported same-sex partnerships.

PMID- 8251873
TI  - Subjective predictions of outcome among alcoholics.
AB  - This study examines the importance of Subjective Staff Ratings as predictors of
      the 3- and 12- month outcomes in 375 male primary alcoholic inpatients. For short
      term outcome, while combinations of more usual predictors including two aspects
      of the pretreatment drinking history, evidence of a stable personal relationship,
      prior alcoholic hospitalizations, employment status, and posttreatment recovery
      home placement explained up to 5% of the variance on three measures of short-term
      outcome, Subjective Ratings alone explained up to 6%. The combination of
      Subjective Ratings and objective historical data explained up to 9% of the
      variance. The data indicate that it is difficult to accurately predict short term
      outcome among primary alcoholics, that the Subjective Ratings of prognosis by the
      treatment staff are important predictors of short-term outcome which do not
      overlap greatly with more traditional predictors, but that these ratings appear
      to add little to the longer term outcome prediction.

PMID- 8251874
TI  - Age group differences in response to treatment for problematic alcohol use.
AB  - That structural characteristics act as markers of modified treatment outcome is a
      long standing idea in the alcohol treatment field. In order to test whether
      patient age is a factor to be considered in making treatment assignments, we
      examined data collected under a clinical trial. Two hundred and twenty-nine
      patients were randomly assigned to one of three treatment conditions: extended
      cognitive behavioral treatment (CB), relationship enhancement (RE), or
      relationship and vocational enhancement (VE). This paper reports on outcome
      (alcohol use) 3-6 months after treatment assignment. Our question was, would
      different age groups assigned to the treatment conditions exhibit different
      outcomes? There were no significant main effects by either treatment condition or
      age group. There was a significant treatment condition by age group interaction.
      With increasing age, the differences in treatment seemed to increase. For the
      younger aged group (18-29 years old) no statistically significant treatment
      differences were detected. Middle aged patients (30-49 years old) did best in the
      RE condition. Older aged patients (50 + years old) did best when assigned to the
      CB condition. These findings lead us to conclude that patient age is a variable
      which should be considered when testing patient-treatment matching hypotheses.

PMID- 8251875
TI  - Heavy drinking in hospital patients.
AB  - The study examines the prevalence of high consumption of alcohol among the
      patients of a large university hospital, and the ability of physicians to detect
      heavy drinking. According to self-report, the results of CAGE questionnaire or
      the physicians' opinion, 25% of the male and 11% of the female patients were
      heavy drinkers. The physicians identified 43% and 26% of the men and women who
      screened positively either according to CAGE or self-report. On the other hand,
      17% of the men and 14% of the women who were identified by the physicians as
      heavy drinkers had a negative screening result. Heavy drinking was most often
      connected with psychiatric disorders, but it was present in all specialties. A
      wide range of diagnoses were found among abusers. It is concluded that all
      patients in all clinics should be asked about their drinking habits instead of
      relying solely on the physician's instinct or on the patient's self-report or
      CAGE. More individual interviews should be done to make possible early
      intervention in heavy drinking.

PMID- 8251876
TI  - The effect of parents' alcohol problems on children's behaviour as reported by
      parents and by teachers.
AB  - Associations between parents' alcohol problems when children were aged 9 and
      children's behaviour at ages 9 and 13 as reported by parents and teachers were
      investigated. The sample consisted of participants in a multidisciplinary
      longitudinal study, data were collected by face-to-face interview. When compared
      to children with no or mild parental alcohol problems, children classified as
      having severe parental alcohol problems were more likely to display high levels
      of problem behaviour at age 9 as reported by teachers and at age 13 as reported
      by parents. Poorer family relationships, lower verbal and reading proficiency and
      being male were also associated with high levels of behaviour problems.

PMID- 8251877
TI  - Alcohol consumption in the European community: uniformity and diversity in
      drinking patterns.
AB  - Within the European Community (EC) drinking patterns in the southern countries
      can be characterised by daily consumption of wine at meals, and in the northern
      countries by less frequent consumption of beer outside meals. Yet, as in past
      decades in the southern countries beer consumption and in the northern countries
      wine consumption strongly increased, the question is whether the distinction in
      drinking patterns still applies. This paper (1) describes for each country of the
      EC total alcohol consumption, (2) examines the frequency and the context of
      consumption of the new beverage type and (3) analyses whether subpopulations,
      defined by sex, age and educational level, differ in the adoption of the new
      beverage type. In all countries wine is consumed more often at meals compared to
      beer. Older people consume wine in greater numbers and more frequently than
      younger people, who consume beer in greater numbers. People of higher educational
      level consume the new beverage type more often compared to people of lower
      educational level, who consume the traditional beverage type more frequently.
      Finally, males and females differ less in the frequency of consumption of the new
      beverage type than in the frequency of the traditional beverage type.

PMID- 8251878
TI  - Attachment among adult children of alcoholics.
AB  - Disturbed or impoverished relationships have been identified as a predominant
      feature of adult children of alcoholics (ACOAs). Recently, the concept of co
      dependency has been advanced to depict the interpersonal difficulties of these
      individuals, but lacks definitional rigor. The notion that childhood experiences
      with parents are 'carried forward' to affect attitudes and behaviors relevant to
      later intimate relationships is also consistent with attachment theory. This
      study examined the patterns of attachment of ACOAs as compared to adult children
      of non alcoholics (ACONAs). A cross-sectional sample of 203 individuals attending
      either a short term hospital based outpatient psychiatric program or a community
      based alcoholism treatment program was included in this study. Results supported
      the hypothesis that female ACOAs had a distinctive dysfunctional attachment
      profile. There were no significant differences in the attachment styles of male
      ACOAs as compared to ACONAs, or male substance abusers as compared to non
      abusers.

PMID- 8251879
TI  - Women with alcohol problems: do they relapse for reasons different to their male
      counterparts?
AB  - A sample of 44 women and 50 men attending an alcohol treatment facility were
      assessed on a range of demographic, social and psychological measures in order to
      determine whether women and men relapse for different reasons. Clients were
      monitored for a 3 month period after the initial intake interview whereupon
      follow-up interviews were conducted. The data were analysed by the use of
      survival analysis techniques. The results indicated that there were different
      predictors of relapse across the three levels of post treatment alcohol use
      investigated. Gender differences were present at two of these levels. The
      implications of these differences are discussed.

PMID- 8251880
TI  - Characteristics associated with smoking cessation during pregnancy among working
      class women.
AB  - Although smoking prevalence among pregnant women is highest among those of lower
      socio-economic status, the factors associated with cessation in this high risk
      group are poorly documented. This paper reports on data from a survey of working
      class women in Nottingham and Coventry, who were interviewed 6 months after
      having delivered a baby. It compares the characteristics of the 32 women who quit
      smoking during their pregnancy and were still ex-smokers at the 6 month post
      natal point, with 472 women who had continued to smoke during their pregnancy or
      had returned to smoking in the post-partum period. A logistic regression analysis
      revealed three variables that were independently associated with long term
      cessation-having previously quit for more than 1 week, having a non-smoking
      partner, and believing that the children of smokers are more likely to get
      infections. Among the most disadvantaged, an understanding of how close social
      ties and economic circumstances influence smoking behaviour is crucial, if we are
      to develop more effective smoking cessation intervention strategies for working
      class women.

PMID- 8251882
TI  - Prisoners and HIV/AIDS.

PMID- 8251881
TI  - Depressive symptoms and DSM-III-R alcohol dependence: general population results.
AB  - The DSM-III-R diagnostic criteria for alcohol dependence differ considerably from
      older criteria. We examined the association of depressive mood and symptoms with
      alcohol dependence as defined by DSM-III-R in a national sample of 2627 current
      drinkers. Depressive mood and symptoms were measured with the Center for
      Epidemiologic Studies Depression scale (CESD). A significant univariate
      association between CESD scores and DSM-III-R alcohol dependence was confirmed in
      a multivariate analysis that controlled for demographic characteristics, regular
      use of drugs, alcohol consumption and recent serious interpersonal loss. Issues
      in the study of depression and alcohol dependence are considered, and potential
      future research directions suggested.

PMID- 8251883
TI  - Cytokinetic considerations relevant to development of a successful therapeutic
      strategy in chronic myelogenous leukemia (CML).
AB  - Despite recent important advances in our understanding of the molecular and
      biological abnormalities in chronic myelogenous leukemia (CML) this new knowledge
      has not yet led to significant improvements in treatment. We have reviewed what
      is known and still unknown about some of the important properties of normal and
      leukemic stem cells and later progenitor cells that may be relevant to developing
      improved treatment strategies in the future. Clinical observations and
      experimental evidence strongly suggest that the major expansion of the CML
      population takes place in the intermediate and later maturation compartments
      rather than in the stem cell or early progenitor cell compartments. The expansion
      occurs slowly, probably taking several years to reach a trillion or more cells,
      at which time clinical symptoms begin to develop. The maturing leukemic
      progenitors do not have an increased proliferative rate, but they undergo one or
      more additional divisions and also live longer than comparable normal
      progenitors. Although no quantitative assay system is available to study the
      ultimate proliferative potential of human stem cells, indirect evidence suggests
      that the behavior of leukemic stem cells is not greatly different from that of
      normal stem cells. One important difference is that the leukemic stem cells (or
      early progenitor cells) do not curtail cell production until marrow cell
      densities are reached that are substantially higher than those at which normal
      stem cells cease production. Based on these and other considerations a possible
      future therapeutic strategy is suggested. Any successful treatment program for
      CML will probably depend on the inclusion of some type of specific drug(s) that
      will selectively affect leukemic progenitors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251884
TI  - Fractionation of chronic myelogenous leukemia marrow cells by stroma adherence:
      implications for marrow purging.
AB  - Chronic myelogenous leukemia (CML) progenitor cells have been shown to be
      defective in their ability to adhere to marrow stroma. It was the aim of the
      present study to investigate at the cytogenetic level marrow-derived CML
      clonogenic cells fractionated on the basis of their ability to adhere to
      preformed, allogeneic, normal marrow-derived stromal layers. Mononuclear marrow
      cells from CML patients (n = 15) were incubated with mafosfamide (100
      micrograms/ml) or control medium, seeded onto marrow stromal layers and allowed
      to adhere (3 hrs, 37 degrees C). Following a short-term liquid culture, the
      different cell fractions were harvested and incorporated in methylcellulose
      cultures. CFU-GM grown from these cultures were analyzed by single colony
      karyotyping. On direct cytogenetic analysis, the overall mean (+/- SD) percentage
      of Ph-negative metaphases was 7 +/- 20%. Following stroma adherence and shortterm
      suspension culture, the mean (+/- SD) percentages of Ph-negative clones were as
      follows: 33 +/- 25% for adherent CFU-GM, 59 +/- 40% for adherent, mafosfamide
      treated CFU-GM, 12 +/- 16% for non-adherent CFU-GM, and 32 +/- 26% for non
      adherent-mafosfamide-treated CFU-GM. If only the patients showing a percentage of
      Ph-negative clones > or = 20% were included in this analysis, the mean (+/- SD)
      percentages of Ph-negative clones were 47 +/- 19% for adherent CFU-GM, and 81 +/-
      21% for adherent-Mafosfamide-treated CFU-GM. In contrast, the majority of pH
      positive CFU-GM were detected within the stroma non-adherent cell
      fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251885
TI  - The cytogenetic scenario of chronic myeloid leukemia.
AB  - The Philadelphia chromosome (Ph), i.e., the reciprocal translocation
      t(9;22)(q34;q11), is found with great specificity in bone marrow cells from
      patients with chronic myeloid leukemia (CML). Variant Ph-producing
      translocations, seen in 5-10% of all patients, are all complex and involve the
      same molecular rearrangement as the regular t(9;22). Patients with classic and
      variant Ph-producing translocations are clinically and hematologically identical,
      and as a group differ from Ph-negative CML patients. In all patient groups, the
      occurrence of additional chromosome changes is an ominous sign indicating that
      disease progression is imminent. The chromosome changes occurring in excess of
      the Ph in CML are clearly nonrandom and two pathways of cytogenetic evolution may
      be distinguished. Major route changes comprise trisomy 8, i(17q), trisomy 19, and
      an extra Ph; totally, 71% of Ph-positive CML patients have at least one of these
      four major route changes. Six minor route changes, including five numerical
      abnormalities (-7, -17, +17, +21, and -Y) but also one structural aberration,
      t(3;21) (q26;q22), have been identified. At least one of these changes is found
      in 15% of all Ph-positive CML cases. Altogether, the four major route aberrations
      and the six minor route changes are present as part of the clonal evolution in
      86% of CML with cytogenetic abnormalities in addition to the Ph chromosome.

PMID- 8251886
TI  - Interferon-alpha effects on stromal compartment of normal and chronic myeloid
      leukemia hematopoiesis.

PMID- 8251887
TI  - Inhibition of P210 expression in chronic myeloid leukaemia: oligonucleotides
      and/or transduced antisense sequences.
AB  - There is now strong evidence that the BCR-ABL gene product (P210) of the
      Philadelphia chromosome plays a crucial role in the pathogenesis of chronic
      myeloid leukaemia (CML). That is why antisense strategies aiming at inhibiting
      P210 expression for research or therapeutic purposes are increasingly
      investigated. Two main tools are currently available in this respect:
      oligonucleotides and retrovirally transduced antisense sequences. In this paper,
      we discuss the potential advantages and drawbacks of each approaches and report
      experimental evidences showing the feasibility of the second one in a murine
      lymphoid cell line (BaF3) expressing P210 upon retroviral transduction of the
      complete BCR-ABL cDNA. A retroviral vector was used to introduce selected
      antisense and sense sequences into this cell line, that P210 expression had
      rendered Interleukin-3 (IL3) independent. The antisense transcripts generated
      under the control of MoMLV promoter specifically killed BaF3 cells in the absence
      of IL3 and stably inhibited P210 expression. Retrovirally transduced antisense
      sequences can thus successfully achieve stable suppression of P210 and may be
      used to study further the mechanisms by which P210 is transforming cells. The
      effect on CML cell lines and fresh CML cells, in bone marrow cultures, remains to
      be investigated before considering this technique for in vitro selective
      suppression of Philadelphia-positive haematopoiesis.

PMID- 8251888
TI  - An overview of some studies of chronic myelogenous leukemia: biological-clinical
      observations and viewing the disease as a chaotic system.
AB  - While much is known about CML at both the clinical and molecular biological
      levels, the precise relationship between the disease at these two levels is
      unclear. The appearance of the fusion gene bcr-abl and disorders in the
      regulation of the myc gene, and perhaps other oncogenes which code for
      nucleoproteins, appear to play integral roles in the genesis of the chronic and
      blastic phases of the disease. The resistance of this disease to cytotoxic
      therapy appears to reflect both "classical" drug resistance and the ability of
      those cells which survive cytotoxic therapy to rapidly replace the killed cells
      thereby offsetting the effects of chemotherapy ("regrowth resistance"). The
      clinical evolution of the disease is compatible with two fundamentally different
      processes: one compatible with a deterministic chaotic model and the other
      involves two basically independent linear phenomena which overlap and intersect
      as the blastic phase appears and replaces the chronic phase.

PMID- 8251889
TI  - Treatment of Ph-positive chronic myeloid leukemia with alpha-interferon (ROFERON
      A). The Italian Cooperative Study Group experience. The Italian Cooperative Study
      Group on Chronic Myeloid Leukemia.
AB  - This is an interim report of two National studies of human recombinant interferon
      alpha 2a (ROFERON-A) in Ph+ chronic myeloid leukemia (CML). The first study (1986
      1988) enrolled 322 patients who were randomized to treatment by IFN or by
      hydroxyurea. Karyotypic responses were more frequent and better with IFN and as
      of June 1992 chronic phase duration and survival of IFN treated pts are projected
      to be significantly longer. The second study (1989-1991) recruited 275 pts less
      than 56 years old, who were given ROFERON-A for 1 year with the aim of obtaining
      a karyotypic response, to collect and cryopreserve the responsive marrows, and
      intensify treatment by high dose busulfan and melphalan followed by autologous
      marrow infusion.

PMID- 8251890
TI  - The German CML study, comparison of busulfan vs. hydroxyurea vs. interferon alpha
      and establishment of prognostic score 1.
AB  - From July 1983 to January 1991 a total of 622 patients were randomized (585
      eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and
      busulfan on the duration of chronic phase, and survival. Further goals included
      the determination of prognostic parameters. 598 CML patients were documented and
      575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients
      were Ph-positive (+). 11% had additional chromosome aberrations. The median
      survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph
      negative patients are older, tend to have lower cell counts and, as a group are
      more ill at diagnosis. A survival difference of about one year is expected
      between busulfan and hydroxyurea treated patients. Prospectively evaluated age,
      organomegaly related symptoms, Karnofsky index, extramedullary manifestations,
      number of erythroblasts and percent of circulating blasts proved to be of
      prognostic significance. A prognostic score (score 1) was determined which was
      superior to Sokal's score in the study population. 164 patients were randomized
      to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse
      effects, therapy resistance or other reasons. Clinically relevant neutralizing
      antibodies were detected in 9 cases. Most frequent adverse events were flu-like
      symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric
      symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13%
      of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions
      were observed, in three of these ongoing. Cytogenetic responders have a survival
      advantage. Interferon treated Philadelphia-negative CML patients have no survival
      disadvantage. The study is expected to allow statements as to the advantages or
      disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML
      as well as to the reliability of prognostic markers.

PMID- 8251891
TI  - Long-term follow-up results of alpha interferon therapy in chronic myelogenous
      leukemia at M. D. Anderson Cancer Center.

PMID- 8251892
TI  - Interferon alpha 2A in the treatment of chronic myelogenous leukemia in chronic
      phase. Results of the Spanish Group.
AB  - Fifty-one patients with CML in chronic phase, less than two years after
      diagnosis, were included in one multicentric study aiming to assess the
      therapeutic value of interferon alpha 2a (IFN alpha 2a) in this setting. The
      therapeutic scheme was biphasic: The patients were first treated with
      hydroxyurea, and afterwards only received IFN alpha 2a, at a planned dose of
      5MU/m2/day, s.c. Thirty-eight patients (81%) achieved an hematologic response,
      which was complete in 57% of the total group. The median time to response was of
      42 days. In the last evaluation, a complete hematologic response was sustained in
      21 patients (47%). Philadelphia suppression was obtained in 44% of the patients
      who achieved hematologic responses; major cytogenetic responses were obtained in
      16% of the patients. The patients who obtained genetic responses were
      significantly younger and had a shorter interval from diagnosis to IFN than the
      patients who did not respond. At the moment of evaluation, 90% of the patients
      are alive, but the median follow-up of the series (217 days, range 21-1150) is
      too short to analyze any impact of IFN over survival. Six patients (12%)
      discontinued IFN because of toxicity, three of them because of severe flu-like
      syndrome. Leukopenia and thrombocytopenia were frequent, but rarely severe.
      Hypertriglyceridemia has been a very frequent finding.

PMID- 8251893
TI  - A multicentric randomised study of alpha 2b interferon (IFN) and hydroxyurea (HU)
      with or without cytosine-arabinoside (Ara-c) in previously untreated patients
      with Ph+ chronic myelocytic leukemia (CML): preliminary cytogenetic results.
AB  - The CML 88 study was designed to evaluate the efficacy of maintenance therapy in
      a multicentric randomised protocol using IFN combined with low-dose Ara-C versus
      IFN alone, following an induction with IFN + HU. Between April 1988 and February
      1991, 237 patients from 36 French Hematology Centres were entered in the study.
      Preliminary cytogenetic results show a slightly higher, although not
      statistically significant, proportion of major chromosomal responses, including
      complete cytogenetic remissions, in the IFN + Ara C arm.

PMID- 8251894
TI  - Ph-positive leukemia: a transgenic mouse model.
AB  - The presence of the BCR/ABL chimeric gene is the hallmark of defined types of
      human leukemia. To increase our knowledge of the oncogenic processes and to
      develop a model for this type of leukemia we generated a BCR/ABL (P190)
      transgenic mouse line. Over 95% of mice of this line die of leukemia or
      leukemia/lymphoma within 35-200 days of age. Karyotypically visible genetic
      alterations were absent from the early stages of BCR/ABL generated leukemia. A
      high frequency of aneuploidy was found in advanced leukemia indicating a primary
      and pivotal role for BCR/ABL in leukemogenesis. Moreover, the data suggest that
      BCR/ABL has a destabilizing effect on the regulation of the cell cycle. BCR/ABL
      expression was also found in tissues other than hematopoietic cells. However,
      this did not result in the development of solid tumors, strongly suggesting that
      the oncogenicity of BCR/ABL is limited to the hematopoietic lineage.

PMID- 8251895
TI  - Treatment of chronic myeloid leukemia with interferon alpha (Roferon): results of
      the Israeli Study Group on CML.
AB  - Thirty patients with chronic myeloid leukemia from 11 Israeli medical centers
      entered this study. Their ages ranged from 16-65 (median 41) and time from
      diagnosis to treatment was 1-16 months (median 4 months). After cytoreductive
      therapy with hydroxyurea (22 patients) or busulphan (8 patients), patients
      received 9 million units/day of recombinant interferon alpha-2 alpha (Roferon A)
      subcutaneously. Side effects included arthralgia or low back pain in 7 patients,
      thrombocytopenia in 9, weight loss in four, neurologic disturbances in 4 and
      leukopenia in 3 cases. Seventeen patients achieved complete hematologic remission
      (CHR) and 6 partial hematologic remission (PHR). Six patients achieved major
      cytogenetic response, 4 of them lost all Ph1 chromosome positive cells and 4 had
      minimal cytogenetic response. Frequency of relapse was high: 8 patients with CHR
      and 6 with PHR relapsed, but patients with major cytogenetic response did not
      relapse. Patients who had received prior therapy with busulphan had a higher
      remission rate but a lower quality of cytogenetic response. Escalation of Roferon
      to 12 million units per day in relapsing or nonresponding patients induced PHR in
      2/7. Neutralizing anti-interferon antibodies occurred in 7 relapsing or
      nonresponding patients. The cytoreductive induction with hydroxyurea enhanced the
      hematologic remissions to a median of 6 weeks. Further studies should define the
      role of combination therapy in order to improve response and prevent relapses.

PMID- 8251897
TI  - Is there any future for T-cell depleted bone marrow transplantation in chronic
      myeloid leukaemia?
AB  - There is no doubt that the poor reputation of T-cell depleted bone marrow
      transplant arises from its use in CML patients, where an increase in graft
      rejection and, above all, in leukaemia relapse has been reported by almost all
      centres. Evidence suggests that the standard conditioning regimen (once thought
      to be sufficiently immunosuppressive and myeloablative in unmanipulated
      transplants) should no longer be considered adequate when the immunological
      balance has shifted in favour of unopposed host-versus-graft reactivity and the
      GvL effect is lacking. Since GvHD remains the major problem in BMT, we suggest T
      cell depletion should be considered the most effective method for GvHD
      prophylaxis but the cytoreductive effect of the conditioning regimens and the
      anti-leukaemia immune reactivity should be enhanced.

PMID- 8251896
TI  - Busulfan and cyclophosphamide versus cyclophosphamide and total body irradiation
      for marrow transplantation in chronic myelogenous leukemia--a review.
AB  - Allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia
      (CML) offers the only significant chance of cure for this disease. About 50% of
      patients transplanted in the 1980s appear to be cured and with subsequent
      advances, it is suggested that more patients transplanted in the 1990s will be
      cured. Cyclophosphamide (Cy) (120 mg/kg) followed by fractionated total body
      irradiation (TBI) (Cy2/TBI) has been usually employed in preparation for BMT.
      Alternative regimens of Busulfan (Bu) (16 mg/kg) and Cy (120 mg/kg) (Bu/Cy2) or
      Bu (16 mg/kg) and Cy (200 mg/kg) (Bu/Cy4) have more recently been employed. At
      least three studies of Bu/Cy2 or Bu/Cy4 have given encouraging results. Two
      ongoing randomized studies of Bu/Cy2 versus Cy2/TBI have shown no difference in
      the event free survival (EFS). In addition, two ongoing randomized studies of
      Bu/Cy4 versus Cy (200 mg/kg) plus TBI (Cy4/TBI) show no significant differences
      in EFS. It appears that Bu/Cy regimens are as effective as Cy/TBI regimens. The
      choice of one regimen over the other depends on matters other than therapeutic
      efficacy.

PMID- 8251898
TI  - Treatment of CML with unrelated donor marrow transplant.
AB  - Chronic myelogenous leukemia (CML) is a uniformly lethal malignant disorder of
      the hematopoietic stem cell. Although CML cannot be cured with conventional
      therapy, recent results suggest that therapy with marrow transplantation may
      prolong survival and, in some cases, provide curative therapy. Approximately 30%
      of otherwise eligible marrow transplant candidates have an HLA matched or one
      antigen mismatched related donor. Related donor marrow transplantation therapy
      for patients in the chronic phase of CML results in 45-70% long-term, disease
      free survival. Younger recipient age, transplant in chronic rather than advanced
      phase and transplant within one year of diagnosis provide a better outcome. Graft
      versus host disease (GVHD), pneumonia and systemic infections are commonly
      encountered complications. T-lymphocyte depletion of donor marrow reduces the
      incidences of acute and chronic graft versus host disease but is associated with
      a higher relapse rate and lower overall incidence of disease-free survival than
      use of non-T-depleted marrow. The use of HLA matched or one antigen mismatched
      unrelated donors allow successful marrow transplantation in approximately 30% of
      CML cases where a suitably matched related donor is not available. Unrelated
      donor marrow transplantation can provide stable engraftment in the majority of
      recipients and lead to leukemia-free survival in many cases. The beneficial
      effects of unrelated donor marrow transplantation are particularly apparent in
      young, chronic phase recipients and when performed using donor/recipient pairs
      identical at the HLA A, B and DR loci. A higher incidence of graft failure and
      GVHD than observed in sibling marrow transplant as well as prolonged
      convalescence in some cases can be anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251899
TI  - What does one do for the CML patient in relapse after allogeneic bone marrow
      transplantation?
AB  - The management of CML patients with some evidence of disease after BMT depends on
      the molecular, cytogenetic and hematological findings of relapse. Presently, a
      number of technical and biological problems do not allow to draw any definitive
      conclusion on the prognostic significance of Minimal Residual Disease detected by
      PCR. A positive PCR, particularly if observed late after BMT, leads to increase
      the frequency of cytogenetic examinations, but a therapeutic intervention is not
      justified. The criteria to define the cytogenetic relapse are not still
      established. Therefore it is difficult to interpret the reappearance of Ph-1
      chromosome after BMT as disease recurrence invariably progressing towards the
      hematological phase. However, alpha-Interferon, donor buffy-coat infusion or
      their association should be considered in the treatment of patients for whom the
      cytogenetic relapse has been confirmed. The therapeutic approach to patients with
      hematological relapse is mainly depending on the phase of disease. The single,
      sequential or combined use of chemotherapy, alpha-IFN, donor buffy-coat infusion
      and second transplant has been shown to be effective in restoring donor
      hematopoiesis in several patients who relapsed either in chronic or advanced
      phase. Prospective, randomized, multicentre trials on CML relapse after BMT
      should be planned.

PMID- 8251900
TI  - The graft versus leukemia (GVL) effect after allogeneic bone marrow
      transplantation for chronic myelogenous leukemia (CML).
AB  - Immune mechanisms superimposed to the myeloablative conditioning regimens exert
      an additional powerful effect in eradicating leukemia and in achieving
      immunological control of minimal residual disease. The impact of GVHD-independent
      GVL has been evaluated to be absent, or near absent, in ALL, about 30% in AML and
      about 40% in CML. While until little time ago most of the evidence in favor of an
      immune antileukemia mechanism exerted by allo BMT in CML was indirect, based on
      the lack of GVL, there is now solid evidence of a positive type, based on the
      antileukemia effect of donor lymphocyte infusions in patients having relapsed
      after transplant. There are three lines of indirect clinical evidence for GVL in
      CML: they include the classical linkage between GVHD and reduced relapse rate,
      increased relapse rate after identical twin allografts, and increased relapse
      risk after effective GVHD prophylaxis, with T lymphocyte depletion in the
      foreground. The eradicating effects of donor lymphocyte infusions in relapsed
      patients are the ultimate demonstration that allogeneic immune competent cells
      are capable of recognizing and destroying the Ph-positive clone. However the
      frequency of irreversible aplasia indicates that donor lymphocytes act in the
      same way on residual host hematopoiesis, so that a second graft, without repeat
      conditioning, should be programmed for such cases.

PMID- 8251901
TI  - Splenic irradiation before bone marrow transplantation for chronic myeloid
      leukemia: update of a prospective randomized study.
AB  - Two hundred and twenty-nine patients with chronic myeloid leukaemia in chronic
      phase awaiting bone marrow transplantation from an HLA-identical sibling donor
      were randomized as part of their conditioning, to receive splenic irradiation
      (SI+, 115 patients), or not (SI-, 114 patients). Both groups were identical in
      regard to age, sex, donor/recipient sex combination and disease activity.
      Survival, leukaemia-free survival, incidence of transplant-related mortality,
      acute and chronic graft versus host disease, incidence of rejection and
      probability of relapse were not different in either groups at a median follow-up
      time of 4.5 years (minimum follow-up 2 years). Recovery of peripheral white blood
      cell counts to 1 x 10(9)/l but not of platelet counts to 50 x 10(9)/l was
      significantly faster in patients with SI+ (21 vs 24 days). This small benefit
      does not justify routine splenic irradiation prior to BMT, in CML.

PMID- 8251902
TI  - Differences between blastic chronic myeloid leukemia and Ph-positive acute
      leukemia.
AB  - Cytogenetic and molecular characteristics of chronic myeloid leukemia in blast
      crisis and Ph-positive acute leukemia are compared. The main differences relate
      to the presence of Ph-negative metaphases at diagnosis and the disappearance of
      Ph in complete remission in acute leukemia, and the localization of the
      chromosome breakpoints in the BCR gene, in the bcr segment in chronic leukemia
      and in the first intron of the BCR gene in 50% of acute leukemias. The profiles
      of these abnormalities, as well as the types of additional chromosome changes,
      are not sufficient to distinguish between the two disorders in every patient. The
      distinction between these two entities, which is possible in the majority of
      patients, will be improved by results of experimental work currently in progress
      in many laboratories.

PMID- 8251903
TI  - Disease progression in a murine model of bcr/abl leukemogenesis.
AB  - We have developed a system for expressing bcr/abl genes in the mouse
      hematopoietic system utilizing retroviral gene transfer and bone marrow
      transplantation. Expression of the P210bcr/abl gene in mice gives rise to a
      spectrum of hematological malignancies, most prominently a myeloproliferative
      syndrome which closely resembles human chronic myelogenous leukemia (CML).
      Studies of this system and related systems in other laboratories have begun to
      yield insights into the pathophysiology of the human bcr/abl leukemias. The CML
      like syndrome appears to be a consequence of infection of a multipotential
      hematopoietic progenitor target cell. The leukemic clone is difficult to
      transplant to secondary recipients, but undergoes evolution to acute leukemia.
      The P190 form of bcr/abl appears to be more potent in leukemogenesis than P210,
      but may also be associated with a CML-like picture upon infection of a
      multipotential target cell. There may be a spectrum of different chronic phase
      duration associated with different Bcr/Abl proteins, with bcr sequences
      influencing the rate of disease progression. In mice, duplication or alterations
      of the bcr/abl gene itself may constitute a major mechanism of disease
      progression.

PMID- 8251904
TI  - The biology of normal and neoplastic stem cells in CML.
AB  - Chronic myeloid leukemia (CML) has long served as a prototype malignancy for
      basic as well as clinical studies aimed at developing curative cancer treatment
      protocols. Well established features of chronic phase CML are its origin in a
      pluripotent stem cell, a now well defined molecular genetic basis involving the
      creation of a BCR-ABL fusion gene and evidence of resultant abnormalities in the
      mechanisms that normally control primitive hemopoietic cell proliferation. We
      have recently shown how the long-term marrow culture system can be adapted to
      quantitate and characterize a very primitive cell type in normal blood and marrow
      samples, as well as their normal and leukemic counterparts in patients with CML.
      This system has also been used to dissect mechanisms of normal progenitor
      regulation and to identify specific anomalies affecting leukemic (CML)
      progenitors. Our studies show that cells detected by their ability to initiate
      long-term cultures (LTC) of leukemic cells (i.e., CML LTC-initiating cells or LTC
      IC) are differently distributed between marrow and blood by comparison to LTC-IC
      in normal individuals and, although functionally similar in terms of the number
      and differentiation types of clonogenic cells they produce, CML LTC-IC exhibit
      defective self-maintenance. Phenotypically these primitive leukemic cells are
      heterogeneous; the majority display features of activated/proliferating cells but
      a significant proportion do not. We have also documented heterogeneity in
      primitive CML cell responses to two factors that specifically and reversibly
      arrest the cycling of primitive normal hemopoietic cells; i.e., TGF-beta and MIP
      1 alpha, to which CML cells are normally responsive and abnormally unresponsive,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251905
TI  - Molecular defects associated with the acute phase CML.
AB  - Parts of the Bcr/Abl hybrid transcript supposed to be important for its
      transforming ability were sequenced in a series of CML blast crises, in order to
      evaluate the possible presence of alterations responsible for the disease
      transition from the chronic to the acute phase. In addition, the N- and Ki-ras as
      well as the p53 involvement was investigated by exploring their structure and
      expression in the same patients. We used traditional types of molecular analysis
      including Southern and Northern blot, together with methods that allow a rapid
      detection of point mutations and microdeletions, such as SSCP, single strand
      conformation polymorphism and direct sequencing. The results obtained may be
      summarized as follows: no alterations were found in the parts of the Bcr/Abl
      transcripts investigated in the present study (SH2, SH3 and the region
      surrounding codon 832); p53 alterations were observed in 5% and N- and Ki-RAS
      mutations in 5% of the cases examined. These molecular defects are therefore
      responsible for the clinical progression of the Ph1-positive CML only in a
      minority of cases.

PMID- 8251906
TI  - Clinical models of autotransplants in chronic myelogenous leukemia.
AB  - We analysed relapse risk after syngeneic and allogeneic T cell depleted
      transplants to predict the outcome after autotransplants in chronic myelogenous
      leukemia (CML). These data suggest that high dose pre-transplant conditioning may
      cure about 50% of the persons in chronic phase and about 10% of those in more
      advanced phases. The expected relapse rate would be about 50-90%. However,
      additional relapses might occur from infusing leukemia cells with the graft.
      Different approaches are being attempted to eliminate leukemia cells from the
      graft. It is however unlikely that their effect could be demonstrated in clinical
      trials. Recent analyses in persons relapsing after allogeneic T depleted
      transplants suggest that reducing the CML cell mass by high dose chemotherapy may
      prolong duration of survival.

PMID- 8251907
TI  - Culture purging in leukemia: past, present, and future.
AB  - Over the past 5 years we have been evaluating the feasibility of using cultured
      marrow autografts to allow patients with chronic myeloid leukemia (CML) to
      receive intensive, potentially curative therapy. The rationale for this approach
      is based on two important findings. The first is that leukemic stem cells
      (operationally defined as Ph-positive long-term culture-initiating cells, or LTC
      IC) are present in the marrow of many CML patients at relatively low levels by
      comparison to co-existing normal stem cells (i.e., Ph-negative LTC-IC). The
      second finding is that leukemic LTC-IC are selectively "purged" following their
      incubation in vitro for 10 days under LTC conditions. As a result, cultured CML
      marrow preparations show, on average, a 300-fold selection in favour of normal
      LTC-IC. However, there is considerable variation in the initial normal and
      leukemic LTC-IC content of marrow samples from different CML patients. Thus in
      only approximately one third of cases does the number of leukemic LTC-IC in the
      marrow decrease to undetectable levels within the first 10 days of culture with
      the number of co-existing normal LTC-IC remaining at or above 1/50th of the
      average value for normal marrow. We have now transplanted 22 such CML patients
      with 10 day cultured marrow autografts following their treatment with
      myeloablative therapy. Fifteen of these patients were in first chronic phase and
      7 had more advanced disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251908
TI  - Photodynamic elimination of clonogenic Ph+ chronic myeloid leukemia cells.
AB  - Benzoporphyrin derivative (BPD) and light is a potent photosensitizer. We
      investigated this modality as a means to selectively eliminate clonogenic Ph(+)
      chronic myeloid leukemia (CML) cells. BPD at 10 ng/ml and 10.8 J/cm2 broad
      spectrum light eliminates from 5 to 6 logs of Ph(+) EM-2 cells. Long-term marrow
      culture studies of treated mixtures of normal and CML cells indicate that
      multipotent progenitor cell viability is retained while cells transcribing BCR
      ABL are not detected. We conclude that BPD and light may offer a means of
      providing CML autografts potentially free of Ph(+) clonogenic cells.

PMID- 8251909
TI  - Karyotypic conversion by interferon as preparative treatment for autologous BMT
      in Ph positive CML. Italian Cooperative Study Group (ICSG) on Chronic Myeloid
      Leukemia.
AB  - This is an interim report of the Roferon A/ABMT protocol by ICSG on CML aimed at
      investigating the feasibility and potential of combining treatment with alpha-IFN
      with ABMT in Ph+ CML. Of 675 Ph+ CML patients recruited between January 1989 and
      January 1991 by 44 Italian institutions, 398 were 55 or less years old and
      eligible for the protocol. Of 132 patients who completed IFN treatment 118 had
      evaluable karyotype; of these only 48 showed > 25% Ph--metaphases and were
      eligible for BM harvest. In 24 patients BM was collected and 13 were submitted to
      ABMT. The major causes of drop out from the protocol were shift to allogeneic
      BMT, accelerated blastic phase, patient refusal and logistic problems. Data on
      hematologic reconstitution are presently available in 11 patients: Neutrophils
      were > 0.5 x 10(9)/l in 23 days (median), (range 16-40 days); platelets reached
      50 x 10(9)/l in 28 days (median), (range 25-100 days). One patient had a very
      delayed BM take and was rescued with autologous peripheral blood stem cells
      collected at diagnosis.

PMID- 8251910
TI  - Newer approaches in treating chronic myelogenous leukemia.
AB  - We evaluated the recovery of human hematopoietic progenitors in long-term bone
      marrow culture (LTBMC) initiated in tissue culture (TC) flasks to that in
      "Lifecell" bags, which are gas-permeable plastic bags in which feeder-layer cells
      cannot adhere. Cells were incubated in presence of IL-1 and IL-3. Our experiments
      reveal sustained hematopoietic stem cell growth in the absence of a feeder layer
      in plastic gas-permeable bags. Evaluations of marrow from patients with chronic
      myelogenous leukemia suggests enrichment of normal hematopoietic precursors.
      Combining effective drugs to decrease Ph(+) clone prior to bone marrow harvest
      and use of cultured bone marrow may provide a useful method for treating patients
      with chronic myelogenous leukemia.

PMID- 8251911
TI  - Autologous blood stem cell transplantation followed by recombinant alpha
      interferon as treatment for patients with high-risk chronic myelogenous leukemia.
      A report of 32 cases.
AB  - Autologous blood stem cell transplantation (ASCT) was performed in 32 patients
      with high risk chronic myelogenous leukemia (CML). Prior to ASCT, the patients
      were given Busulfan and high-dose Melphalan. Peripheral blood stem cells
      collected at diagnosis were used to rescue hematopoiesis. Recombinant Interferon
      was administered after ASCT. In 24 patients transplanted in transformation, 23
      achieved a complete hematological response and nine are still alive 9 to 73
      months after ASCT. Eight other patients were transplanted in chronic phase for
      either the presence of bad prognostic factors (Sokal's classification) or no
      response to IFN. Seven are alive without transformation 16 to 48 months after
      ASCT. Although few patients presented a cytogenetical response (10/28), the
      survival observed in this series of patients compares favorably with that of
      patients treated conventionally. Thus, the place of ASCT in CML could now be
      tested prospectively.

PMID- 8251912
TI  - Recent progress in understanding chronic myelogenous leukemia.
AB  - Several important issues in CML research are not covered in this brief review
      such as the structural or molecular basis of the translocation between ABL and
      BCR, the relationship between CML and ALL with an identical or related BCR/ABL
      abnormality, the biology of CML stem and progenitor cells and immunologic aspects
      of CML. These are discussed elsewhere in this volume. The data reviewed indicate
      considerable progress in understanding the molecular and cell biology of CML.
      More is known about what causes CML than any human cancer. However, many
      important unresolved issues are likely to provide a productive direction for
      future studies.

PMID- 8251913
TI  - The detection of post-therapy residual minimal disease in leukemias characterized
      by specific chromosomal anomalies.
AB  - Chromosomal and Southern Blot analyses have been used to diagnose Leukemias
      characterized by non-random chromosomal rearrangements. They have also been used
      to monitor disease progression during and after chemotherapy. These methodologies
      are often not adequate to detect RMD after ablative therapy and Bone Marrow
      Transplantation (BMT). Molecular quantitative Polymerase Chain Reaction (PCR)
      techniques have been developed to detect low levels of leukemic cells in patients
      with diseases characterised by fusion transcripts. 95% of Chronic Myelocytic
      (CML) and 15-25% of Acute Lymphoblastic Leukemia (ALL) patients are Ph1 producing
      a fusion transcript between the abl proto-oncogene and the bcr gene. Acute
      Promyelocytic Leukemia (APL) with break points in the (RAR) gene and the zyl gene
      also produces a fusion transcript. The significance of PCR for 1) detecting RMD
      after therapy, 2) correlating low levels of leukemic cells over time with
      therapeutic response and long term remission and 3) assessing the effect of RMD
      during remission by sequential analyses is discussed.

PMID- 8251914
TI  - Minimal residual disease after bone marrow transplant for chronic myeloid
      leukaemia detected by the polymerase chain reaction.
AB  - We describe the methodology and application of the polymerase chain reaction to
      detect BCR-ABL mRNA as a marker for CML cells. The technique is highly sensitive
      enabling the routine detection of 1 leukaemic cell in 10(5) or 10(6) normal cells
      and is therefore the most sensitive method available for detecting minimal
      residual disease. Analysis of marrow or blood from 80 patients after bone marrow
      transplantation for CML shows that residual leukemia is often detectable for
      several months but that most subsequently become PCR negative. Patients who
      relapsed were all PCR positive before the detection of Philadelphia positive
      metaphases in bone marrow aspirates.

PMID- 8251915
TI  - The role of myc in transformation by BCR-ABL.
AB  - The BCR-ABL gene plays a central role in the pathogenesis of chronic myelogenous
      leukemia. Despite a detailed understanding of the regions of BCR and ABL required
      for transformation by BCR-ABL, little is known about the signalling pathway by
      which BCR-ABL causes transformation. The nuclear oncogene c-myc plays a critical
      role in BCR-ABL transformation. Levels of c-myc RNA are high in cells transformed
      by BCR-ABL, and overexpression of dominant negative forms of myc blocks
      transformation by BCR-ABL. These findings suggest that myc may be a useful
      therapeutic target in BCR-ABL-related leukemias.

PMID- 8251916
TI  - CML: mechanisms of disease initiation and progression.
AB  - Chronic myelogenous leukemia (CML) is a hematological stem cell disorder
      characterized by excessive proliferation of the myeloid lineage. It has a
      progressive course typified by the transition from the chronic phase to the
      accelerated phase and on to blast crisis. The hallmark of CML is the
      translocation between chromosomes 9 and 22 that results in the chimeric BCR-ABL
      gene encoding p210BCR-ABL. The oncogenic potential of this protein has been
      validated, and it is believed that it contributes in a critical way to the
      initiation of CML. However, the secondary genetic forces responsible for the
      transition from the chronic state to the fully blastic stage are not clear.
      Evidence for chromosomal instability includes the clonal evolution which
      characterizes advanced CML. In regard to specific genetic aberrations, sporadic
      reports have shown alterations in H-RAS, c-MYC, retinoblastoma, and P53 genes, as
      well as production of p190BCR-ABL during the progression of CML. In addition, we
      have recently found evidence for excessive interleukin-1 beta production, acting
      in an autocrine and/or paracrine manner, in the more advanced stages of the
      disease. Taken together, current data suggest that multiple molecular pathways
      lead to disease progression, and that distinct subsets of genetic alterations
      exist in blast crisis patients.

PMID- 8251917
TI  - Structural organization of BCR-ABL gene in chronic phase and blast transformation
      in chronic myeloid leukemia patients.
AB  - We studied 36 DNA samples of 18 patients affected with chronic myeloid leukemia
      (CML) for the presence of mutations in the first exon of the BCR gene was divided
      into four regions amplified by polymerase chain reaction (PCR). By single strand
      conformation polymorphism analysis (SSCP) and direct sequencing of amplified
      fragments, we found different banding profiles in 9 out of 18 patients in the PCR
      fragment spanning nucleotide 506-826. In one patient, sequence analysis revealed
      the presence of a point mutation at nucleotide 669 (A-T; Gln-Leu). No difference
      was found between DNA samples collected during the chronic phase and the blastic
      transformation. No different mobility shifts of single stranded PCR products were
      found in the other amplified fragments. The activation of BCR-ABL involves direct
      interaction between BCR first exon sequences and the tyrosine kinase regulatory
      domains of ABL. In the first BCR exon, and around the mutated sequences two SH-2
      binding sites, are retained. These domains are essential for BCR-ABL-mediated
      transformation. Our results demonstrate the presence of point mutation in this
      regulatory region, which may suggest a role for the altered BCR sequence in
      activation of the BCR-ABL oncogene.

PMID- 8251918
TI  - Animal models of BCR/ABL-induced leukemias.
AB  - Chronic myelogenous leukemia (CML) serves as a valuable paradigm for
      understanding the molecular genetic origins of cancer. The cytogenetic standard
      of diagnosis, the Philadelphia chromosome, has been superseded by a molecular
      definition for the disease, that of BCR/ABL gene rearrangement. The use of
      BCR/ABL to recreate CML in mice fulfills Koch's postulates for molecular
      pathogenesis. The present murine systems facilitate research into the biology of
      BCR/ABL-induced leukemias, but fall short in their promise to provide models for
      testing new therapies for CML. A transgenic strain of mice with an inheritable
      predisposition to CML would be an invaluable tool.

PMID- 8251919
TI  - Prognosis of chronic myeloid leukemia: studies from the Barcelona Group.
AB  - Individual and multicenter efforts have facilitated the recognition of different
      parameters with prognostic value at presentation of chronic myeloid leukemia
      (CML). Interest is currently focused on the prognostic evaluation of features
      obtained from molecular analysis, and isolation of data with evolutive predictive
      value. The site of breakpoint within the M-BCR has been suggested as a prognostic
      factor in some studies. A recent analysis from our group failed to demonstrate
      differences in either duration of chronic phase or survival between patients with
      5' and 3' breakpoints. We have confirmed in a sequential study that a decrease in
      the expression of some myeloid differentiation antigens of the blood granulocytes
      can be a prognostic indicator along CML evolution. Our more recent study,
      separating blast crises on immunological and molecular grounds, confirms lymphoid
      cases as a distinct subgroup and shows a trend for an association between
      megakaryoblastic blast crisis and 3' location of the breakpoint.

PMID- 8251920
TI  - Prognostic factors in chronic myeloid leukemia. Relationship with interferon and
      bone marrow transplantation. The Italian Cooperative Study Group on Chronic
      Myeloid Leukemia.
AB  - To evaluate the prognostic features of Ph+ CML patients treated by allogeneic BMT
      or by IFN, we reviewed the data of 50 consecutive pts who were transplanted
      between 1984 and 1988 and of 180 consecutive patients who were assigned to
      continuous IFN treatment between 1986 and 1988. In the BMT group, Sokal's system
      predicted survival (transplant-associated mortality). In the IFN group, Sokal's
      system, platelet count, and peripheral blood blast cell percentage predicted
      karyotypic response. In this group, survival was related more significantly with
      blast cell than with Sokal's score. The strongest predictor of survival was
      karyotypic response to IFN, with a 4-year survival of 94% for responders vs. 56%
      for non-responders.

PMID- 8251921
TI  - Chronic myeloid leukaemia--the XXI century.
AB  - CML has served as a model for study of pathogenesis, evolution and treatment of
      malignancy for nearly 150 years and will continue to do so. The increasing
      interest worldwide in biology and medicine and the explosion of activity in
      molecular biology make it probable that many forms of leukaemia, lymphoma and
      solid tumours that are lethal today will be readily prevented or cured within the
      next 20 or 30 years.

PMID- 8251922
TI  - The relationship between the location of the breakpoint within the M-bcr and
      clinical parameters.
AB  - The Philadelphia chromosome (t9;22)(q34;q11) is a characteristic abnormality in
      chronic myeloid leukemia. In greater than 95% of the cases, the breakpoint occurs
      with the M-bcr region of the BCR gene on chromosome 22. Several studies have
      attempted to correlate the location of the breakpoint within the M-bcr with a
      clinical parameter. The majority of studies have examined the relationship
      between the site of breakpoint and the median chronic phase duration (CPD). Some
      studies have reported a correlation, with 5' breakpoint patients who have a
      longer median CPD than patients with a 3' breakpoint. However, other groups have
      reported that no correlation exists. Furthermore, data from some of the latter
      groups have suggested that a correlation may exist with the lineage of blast
      crisis which developed and 3' breakpoint patients had a higher than expected
      number of lymphoid blast crisis. A correlation between high platelet counts at
      diagnosis and patients with a 3' breakpoint or those who expressed a b3-a2 BCR
      ABL mRNA has also been described. No consistent conclusion from any of these
      studies can be drawn. This may due, in part, to some degree of patient and sample
      selection, although environmental, genetic or life-style factors may also
      contribute.

PMID- 8251923
TI  - Will molecular biology contribute to refine prognosis and to select treatment?
      The Molecular Biology Committee. Italian Cooperative Study Group on Chronic
      Myeloid Leukemia.
AB  - The possible prognostic value of the position of the breakpoint within the M-BCR
      in patients with Ph1+ CML is still being debated. We analyzed the DNA
      rearrangements and the transcript types of 244 patients and tried to correlate
      the data obtained with prognostic features, defined according to Sokal's risk
      index, and with chronic phase and/or survival duration. The exact location of the
      breakpoint, either 5' or 3' to the Hind III restriction site within the M-BCR was
      identified. Moreover, the exact M-BCR subregion was also identified. As a whole,
      150 pts were rearranged in the 5' part and 94 in the 3' part of the M-BCR. No
      correlation was observed between the site of rearrangement on the one hand and
      the Sokal's prognostic index and survival, on the other. Transcript analysis was
      performed in 130 patients; 59 carried an a2b2 and 69 an a2b3 pattern. Two
      patients carried both transcripts. Of the patients rearranged in the 5' area,
      according to Southern blotting, 29.2% showed an a2b3 transcript. Therefore, RT
      PCR analysis allowed a better definition of the breakpoint. However, also the
      type of transcript did not show any correlation either with risk categories or
      survival. No difference in response to therapy, either chemotherapy or alpha
      interferon, was observed between 5' and 3' rearranged patients.

PMID- 8251924
TI  - Cell biology of CML--a model linking the chronic and terminal phases.
AB  - A model for the pathogenesis of chronic myeloid leukaemia (CML) is proposed. It
      relies on a comparison between normal steady-state and regenerating haemopoiesis
      and suggests that chronic phase CML stem cells have a finite capacity for self
      renewal. According to the model, metamorphosis of the disease occurs once the
      potential for chronic phase cell production has been exhausted. The model
      considers also the generation of leukocytosis in the chronic phase and the origin
      of the terminal phase. Comparison with normal regenerating haemopoiesis allows
      discrimination between features of CML that are fundamentally abnormal and those
      which are normally associated with regeneration.

PMID- 8251925
TI  - Effect of vinconate, an indolonaphthyridine derivative, on metabolism and
      function of cerebral cholinergic neurons in rat.
AB  - Effects of (+/-)-methyl 3-ethyl-2,3,3a,4-tetrahydro-1H-indolo [3,2,1,-de] [1,5]
      naphthyridine-6-carboxylate hydrochloride (vinconate), an indolonaphthyridine
      derivative, on the metabolism and function of cerebral cholinergic neurons were
      investigated using male Wistar rats. Single administration of vinconate (5, 50
      and 200 mg/kg) decreased acetylcholine content in the striatum but not those in
      the cerebral cortex and hippocampus. The same treatment with vinconate (5, 50 and
      200 mg/kg, p.o.) had no effect on the activities of choline acetyltransferase and
      acetylcholinesterase in these brain areas. Although the addition of vinconate
      (10(-7) - 10(-4) M) had no effect on the high affinity uptake of [3H]choline into
      striatal slices, it induced a concentration-dependent increase of a KCl(2 x 10(
      2) M)-evoked endogenous acetylcholine release. The addition of (-)-sulpiride (10(
      8) - 10(-6) M), a dopamine D2 receptor antagonist, also accentuated the KCl(2 x
      10(-2) M)-evoked endogenous acetylcholine release form striatal slices.
      Furthermore, it was found that this (-)-sulpiride (10(-7) M)-induced increase of
      endogenous acetylcholine release was further augmented by the addition of
      vinconate (10(-5) M). These results suggest that vinconate may enhance the
      release of endogenous acetylcholine via the modulation of presynaptic dopamine
      heteroreceptor in the striatum.

PMID- 8251926
TI  - Characterization of muscarinic binding sites in the adult and developing rat
      cochlea.
AB  - The maturation of the cholinergic innervation of the rat cochlea is associated
      with a transient increase in the muscarinic-receptor activated inositol phosphate
      synthesis. In order to investigate the mechanisms involved in this transient
      enhancement of the inositol phosphate response, the binding properties of the
      cochlear muscarinic receptors were studied during rat cochlear development.
      Incubating the membranes from 4-day-old, 12-day-old and adult cochleas with
      [3H]quinuclidinyl benzylate indicates that their respective, mean concentrations
      of cholinoceptors are 454 +/- 51 (+/- SEM), 39 +/- 2 and 42 +/- 3 fmol/mg of
      protein. The dissociation constants at equilibrium are 207 +/- 80, 42 +/- 7 and
      28 +/- 3 pM for the binding sites of the 4-day-old, 12-day-old and adult
      cochleas, respectively. Pharmacological characterization of the binding, using
      selective antagonists, shows that M3 cholinoceptors are expressed in developing
      and adult cochleas. The data demonstrate that changes in muscarinic receptor
      affinity and number do not correlate with the previously observed peak of the
      inositol phosphate metabolism. The transient enhanced inositol phosphate response
      is therefore not due to changes in cholinoceptors, but probably due to
      alterations involving the intrinsic activity of the phospholipase C and/or the
      efficacy of coupling of the transduction system.

PMID- 8251927
TI  - Influence of ethanol on cadmium accumulation and its impact on lipid peroxidation
      and membrane bound functional enzymes (Na+, K(+)-ATPase and acetylcholinesterase)
      in various regions of adult rat brain.
AB  - Influence of ethanol on cadmium accumulation and its effect on metallothionein
      induction, binding of cadmium to metallothionein, lipid peroxidation and membrane
      bound functional enzymes such as (Na(+)-K+)-ATPase and acetylcholinesterase in
      various regions of adult rat brain was investigated. Ethanol (2 g/kg body wt) and
      cadmium (1 mg/kg body wt) were administered alone as well as in combination to
      different groups of rats, i.p., for a period of 1 week. It was observed that
      cadmium when co-administered with ethanol led to pronounced increase in cadmium
      accumulation in various regions of the brain. This ethanol induced accumulation
      of cadmium did not induce the synthesis of metallothionein and also did not bind
      to this protein in brain and mainly was present as non-metallothionein bound
      cadmium. It lead to a significant increase in lipid peroxidation and inhibition
      of membrane bound functional enzymes; (Na(+)-K+)-ATPase and acetylcholinesterase
      in various regions of the brain indicating functional impairment. The results of
      the present study imply that ethanol renders the adult brain more susceptible to
      cadmium neurotoxicity. Corpus striatum and cerebral cortex are more vulnerable
      regions than other areas of the brain.

PMID- 8251928
TI  - Effect of 4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydropyridine
      , an analog of MPTP, on mouse heart norepinephrine and brain catecholamines.
AB  - An analog of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) with a
      thiadiazole substituent in place of the phenyl ring was compared to MPTP in mice
      for its ability to deplete striatal dopamine and its metabolites and
      norepinephrine in the frontal cortex and heart. One week after the last of 4
      daily s.c. injections, MPTP at 20 mg/kg depleted mouse striatal dopamine, DOPAC
      and HVA as well as norepinephrine in the frontal cortex. One week after 4 daily
      s.c. doses of 4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydro pyr
      idine (MZTP) at doses as high as 80 mg/kg, there was no effect on brain
      catecholamines. A single dose of MPTP (10 mg/kg s.c.) depleted heart
      norepinephrine concentration 24 h after injection. MZTP had no effect on heart
      norepinephrine at 10 mg/kg s.c., but did significantly deplete mouse heart
      norepinephrine 24 h after a dose of 20 mg/kg s.c.

PMID- 8251929
TI  - Postnatal development of ATPase-ADPase activities in synaptosomal fraction from
      cerebral cortex of rats.
AB  - ATPase-ADPase activities in synaptosomes from cerebral cortex was measured in
      rats of various ages (0-, 7-, 10-, 14- and 21- and 60-90-days). The activities
      (nmol Pi/min/mg) increased steadily from birth, reaching maximum values at 21
      days of age. The increase was primarily due to increases in Vmax; the Km values
      are the same from birth until adult age. The developmental profile was similar
      for ATPase-ADPase activities and acetylcholinesterase from the same fraction.
      Several specific ATPase inhibitors and Ap5A (P1P5-di(adenosine-5)-pentaphosphate)
      did not interfere with the hydrolysis of ATP and ADP at all ages studied,
      suggesting that classical ATPases and adenylate kinase were not involved in the
      degradation of both nucleotides by synaptosomal fraction in the assay conditions.
      Other phosphatases were also ruled out. It is conceivable that ATPase-ADPase
      activities play an important role in neurotransmitter metabolism.

PMID- 8251930
TI  - Iron/ascorbate-induced lipid peroxidation changes membrane fluidity and
      muscarinic cholinergic receptor binding in rat frontal cortex.
AB  - Lipid peroxidation (LP) is a complex process which involves the formation of
      lipid free radicals and leads to oxidative damage. LP has also been implicated in
      several neurodegenerative diseases as well as aging. In the present study, we
      evaluated the effects of the induction of LP in vitro on muscarinic cholinergic
      (Mch) receptor binding and membrane fluidity in rat brain. Membranes from the rat
      frontal cortex were peroxidized by adding ferrous sulphate (84 microM) and
      ascorbic acid (400 microM). Peroxidation was measured as the amount of
      thiobarbituric acid reactive products formed (nmol malondialdehyde/mg protein).
      Mch receptor binding was measured 10, 20 and 30 min after peroxidation. Membrane
      fluidity was evaluated by fluorescence polarization studies using two probes; 1,6
      diphenyl-1,3,5-hexatriene (DPH) and 1-[4(trimethylamino)phenyl]-1,3,5-hexatriene
      (TMA-DPH). Significant alterations in Mch receptor binding (decreased Bmax and
      increased Kd) were found after peroxidation. Membrane fluidity was also
      significantly decreased after peroxidation as observed with both probes. The
      decrease in membrane fluidity was due to an increased cholesterol to phospholipid
      molar ratio after peroxidation. These data suggest that lipid peroxidation
      induces changes in membrane dynamics as detected by the fluorescent probes and
      such changes in membrane microviscosity may be the cause for alterations in Mch
      receptor kinetics.

PMID- 8251931
TI  - Disulfide bonds and the stability of globular proteins.
AB  - An understanding of the forces that contribute to stability is pivotal in solving
      the protein-folding problem. Classical theory suggests that disulfide bonds
      stabilize proteins by reducing the entropy of the denatured state. More recent
      theories have attempted to expand this idea, suggesting that in addition to
      configurational entropic effects, enthalpic and native-state effects occur and
      cannot be neglected. Experimental thermodynamic evidence is examined from two
      sources: (1) the disruption of naturally occurring disulfides, and (2) the
      insertion of novel disulfides. The data confirm that enthalpic and native-state
      effects are often significant. The experimental changes in free energy are
      compared to those predicted by different theories. The differences between theory
      and experiment are large near 300 K and do not lend support to any of the current
      theories regarding the stabilization of proteins by disulfide bonds. This
      observation is a result of not only deficiencies in the theoretical models but
      also from difficulties in determining the effects of disulfide bonds on protein
      stability against the backdrop of numerous subtle stabilizing factors (in both
      the native and denatured states), which they may also affect.

PMID- 8251932
TI  - Crystal structures of the myristylated catalytic subunit of cAMP-dependent
      protein kinase reveal open and closed conformations.
AB  - Three crystal structures, representing two distinct conformational states, of the
      mammalian catalytic subunit of cAMP-dependent protein kinase were solved using
      molecular replacement methods starting from the refined structure of the
      recombinant catalytic subunit ternary complex (Zheng, J., et al., 1993a,
      Biochemistry 32, 2154-2161). These structures correspond to the free apoenzyme, a
      binary complex with an iodinated inhibitor peptide, and a ternary complex with
      both ATP and the unmodified inhibitor peptide. The apoenzyme and the binary
      complex crystallized in an open conformation, whereas the ternary complex
      crystallized in a closed conformation similar to the ternary complex of the
      recombinant enzyme. The model of the binary complex, refined at 2.9 A resolution,
      shows the conformational changes associated with the open conformation. These can
      be described by a rotation of the small lobe and a displacement of the C-terminal
      30 residues. This rotation of the small lobe alters the cleft interface in the
      active-site region surrounding the glycine-rich loop and Thr 197, a critical
      phosphorylation site. In addition to the conformational changes, the
      myristylation site, absent in the recombinant enzyme, was clearly defined in the
      binary complex. The myristic acid binds in a deep hydrophobic pocket formed by
      four segments of the protein that are widely dispersed in the linear sequence.
      The N-terminal 40 residues that lie outside the conserved catalytic core are
      anchored by the N-terminal myristylate plus an amphipathic helix that spans both
      lobes and is capped by Trp 30. Both posttranslational modifications,
      phosphorylation and myristylation, contribute directly to the stable structure of
      this enzyme.

PMID- 8251933
TI  - Identification, classification, and analysis of beta-bulges in proteins.
AB  - A beta-bulge is a region of irregularity in a beta-sheet involving two beta
      strands. It usually involves two or more residues in the bulged strand opposite
      to a single residue on the adjacent strand. These irregularities in beta-sheets
      were identified and classified automatically, extending the definition of beta
      bulges given by Richardson et al. (Richardson, J.S., Getzoff, E.D., & Richardson,
      D.C., 1978, Proc. Natl. Acad. Sci. USA 75, 2574-2578). A set of 182 protein
      chains (170 proteins) was used, and a total of 362 bulges were extracted. Five
      types of beta-bulges were found: classic, G1, wide, bent, and special. Their
      characteristic amino acid preferences were found for most classes of bulges.
      Basically, bulges occur frequently in proteins; on average there are more than
      two bulges per protein. In general, beta-bulges produce two main changes in the
      structure of a beta-sheet: (1) disrupt the normal alternation of side-chain
      direction; (2) accentuate the twist of the sheet, altering the direction of the
      surrounding strands.

PMID- 8251934
TI  - Solution structure of the calcium channel antagonist omega-conotoxin GVIA.
AB  - The three-dimensional solution structure is reported for omega-conotoxin GVIA,
      which is a potent inhibitor of presynaptic calcium channels in vertebrate
      neuromuscular junctions. Structures were generated by a hybrid distance geometry
      and restrained molecular dynamics approach using interproton distance, torsion
      angle, and hydrogen-bonding constraints derived from 1H NMR data. Conformations
      of GVIA with low constraint violations converged to a common peptide fold. The
      secondary structure in the peptide is an antiparallel triple-stranded beta-sheet
      containing a beta-hairpin and three tight turns. The NMR data are consistent with
      the region of the peptide from residues S9 to C16 being more dynamic than the
      rest of the peptide. The peptide has an amphiphilic structure with a positively
      charged hydrophilic side and an opposite side that contains a small hydrophobic
      region. Residues that are thought to be important in binding and function are
      located on the hydrophilic face of the peptide.

PMID- 8251936
TI  - Stabilization of creatinase from Pseudomonas putida by random mutagenesis.
AB  - Creatinase (creatine amidinohydrolase, EC 3.5.3.3) from Pseudomonas putida is a
      homodimer of 45 kDa subunit molecular mass, the three-dimensional structure of
      which is known at 1.9 A resolution. Three point mutants, A109V, V355M, and V182I,
      as well as one double mutant combining A109V and V355M, and the triple mutant
      with all three replacements, were compared with wild-type creatinase regarding
      their physical and enzymological properties. High-resolution crystal data for
      wild-type creatinase and the first two mutants suggest isomorphism at least for
      these three proteins (R. Huber, pers. comm.). Physicochemical measurements
      confirm this prediction, showing that the mutations have no effect either on the
      quaternary structure and gross conformation or the catalytic properties as
      compared to wild-type creatinase. The replacement of V182 (at the solvent-exposed
      end of the first helix of the C-terminal domain) does not cause significant
      differences in comparison with the wild-type enzyme. The other point mutations
      stabilize the first step in the biphasic denaturation transition without
      affecting the second one. In sum, the enhanced stability seems to reflect slight
      improvements in the local packing without creating new well-defined bonds. The
      increase in hydrophobicity generated by the introduction of additional methyl
      groups (A109V, V182I) must be compensated by minor readjustments of the global
      structure. Secondary or quaternary interactions are not affected. In going from
      single to double and triple mutants, to a first approximation, the increments of
      stabilization are additive.

PMID- 8251935
TI  - Effect of a single aspartate on helix stability at different positions in a
      neutral alanine-based peptide.
AB  - A single aspartate residue has been placed at various positions in individual
      peptides for which the alanine-based reference peptide is electrically neutral,
      and the helix contents of the peptides have been measured by circular dichroism.
      The dependence of peptide helix content on aspartate position has been used to
      determine the helix propensity (s-value). Both the charged (Asp-) and uncharged
      (Asp0) forms of the aspartate residue are strong helix breakers and have
      identical s-values of 0.29 at 0 degree C. The interaction of Asp- with the helix
      dipole affects helix stability at positions throughout the helix, not only near
      the N-terminus, where the interaction is helix stabilizing, and the C-terminus,
      where it is destabilizing. Comparison of the helix contents at acidic pH (Asp0)
      and at neutral pH (Asp-) shows that the charge-helix dipole interaction is
      screened slowly with increasing NaCl concentration, and screening is not complete
      even at 4.8 M NaCl. Lastly, a helix-stabilizing hydrogen-bond interaction between
      glutamine and aspartate (spacing i, i + 4) has been found. This side-chain
      interaction is specific for both the orientation and spacing of the glutamine and
      aspartate residues and is resistant to screening by NaCl.

PMID- 8251937
TI  - Engineered plant phosphorylase showing extraordinarily high affinity for various
      alpha-glucan molecules.
AB  - alpha-Glucan phosphorylases are characterized by considerable difference in
      substrate specificities, even though the primary structures are well conserved
      among the enzymes from microorganisms, plants, and animals. The higher plant
      phosphorylase isozyme designated as type L exhibits low affinity for a large,
      highly branched glucan (glycogen), presumably due to steric hindrance caused by a
      unique 78-residue insertion located beside the mouth of the active-site cleft,
      whereas another isozyme without the insertion (designated as type H) shows very
      high affinity for both linear and branched glucans. Using the recombinant type L
      isozyme from potato tuber as a starting framework and aiming at altering its
      substrate specificity, we have genetically engineered the 78-residue insertion
      and its flanking regions. Firstly, removal of the insertion and connection of the
      newly formed C- and N-terminals yielded a totally inactive enzyme, although the
      protein was produced in Escherichia coli cells in a soluble form. Secondly, a
      chimeric phosphorylase, in which the 78-residue insertion and its flanking
      regions are replaced by the corresponding region of the type H isozyme, has been
      shown to exhibit high affinity for branched glucans (Mori, H., Tanizawa, K., &
      Fukui, T., 1993, J. Biol. Chem. 268, 5574-5581), but when two and four
      unconserved residues in the N-terminal flanking region of the chimeric
      phosphorylase were mutated back to those of the type L isozyme, the resulting
      mutants showed significantly lowered affinity for substrates.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8251938
TI  - Changes in interactions in complexes of hirudin derivatives and human alpha
      thrombin due to different crystal forms.
AB  - The three-dimensional structures of D-Phe-Pro-Arg-chloromethyl ketone-inhibited
      thrombin in complex with Tyr-63-sulfated hirudin (ternary complex) and of
      thrombin in complex with the bifunctional inhibitor D-Phe-Pro-Arg-Pro-(Gly)4
      hirudin (CGP 50,856, binary complex) have been determined by X-ray
      crystallography in crystal forms different from those described by Skrzypczak
      Jankun et al. (Skrzypczak-Jankun, E., Carperos, V.E., Ravichandran, K.G., &
      Tulinsky, A., 1991, J. Mol. Biol. 221, 1379-1393). In both complexes, the
      interactions of the C-terminal hirudin segments of the inhibitors binding to the
      fibrinogen-binding exosite of thrombin are clearly established, including
      residues 60-64, which are disordered in the earlier crystal form. The
      interactions of the sulfate group of Tyr-63 in the ternary complex structure
      explain why natural sulfated hirudin binds with a 10-fold lower K(i) than the
      desulfated recombinant material. In this new crystal form, the autolysis loop of
      thrombin (residues 146-150), which is disordered in the earlier crystal form, is
      ordered due to crystal contacts. Interactions between the C-terminal fragment of
      hirudin and thrombin are not influenced by crystal contacts in this new crystal
      form, in contrast to the earlier form. In the bifunctional inhibitor-thrombin
      complex, the peptide bond between Arg-Pro (P1-P1') seems to be cleaved.

PMID- 8251939
TI  - Dominant role of local dipoles in stabilizing uncompensated charges on a sulfate
      sequestered in a periplasmic active transport protein.
AB  - Electrostatic interactions are among the key factors determining the structure
      and function of proteins. Here we report experimental results that illuminate the
      functional importance of local dipoles to these interactions. The refined 1.7-A X
      ray structure of the liganded form of the sulfate-binding protein, a primary
      sulfate active transport receptor of Salmonella typhimurium, shows that the
      sulfate dianion is completely buried and bound by hydrogen bonds (mostly main
      chain peptide NH groups) and van der Waals forces. The sulfate is also closely
      linked, via one of these peptide units, to a His residue. It is also adjacent to
      the N-termini of three alpha-helices, of which the two shortest have their C
      termini "capped" by Arg residues. Site-directed mutagenesis of the recombinant
      Escherichia coli sulfate receptor had no effect on sulfate-binding activity when
      an Asn residue was substituted for the positively charged His and the two Arg
      (changed singly and together) residues. These results, combined with other
      observations, further solidify the idea that stabilization of uncompensated
      charges in a protein is a highly localized process that involves a collection of
      local dipoles, including those of peptide units confined to the first turns of
      helices. The contribution of helix macrodipoles appears insignificant.

PMID- 8251940
TI  - In vitro aging of calmodulin generates isoaspartate at multiple Asn-Gly and Asp
      Gly sites in calcium-binding domains II, III, and IV.
AB  - We have determined the major sites responsible for isoaspartate formation during
      in vitro aging of bovine brain calmodulin under mild conditions. Protein L
      isoaspartyl methyltransferase (EC 2.1.1.77) was used to quantify isoaspartate by
      the transfer of methyl-3H from S-adenosyl-L-[methyl-3H]methionine to the
      isoaspartyl (alpha-carboxyl) side chain. More than 1.2 mol of methyl-acceptor
      sites per mol of calmodulin accumulated during a 2-week incubation without
      calcium at pH 7.4, 37 degrees C. Analysis of proteolytic peptides of aged
      calmodulin revealed that > 95% of the methylation capacity is restricted to
      residues in the four calcium-binding domains, which are predicted to be highly
      flexible in the absence of calcium. We estimate that domains III, IV, and II
      accumulated 0.72, 0.60, and 0.13 mol of isoaspartate per mol of calmodulin,
      respectively. The Asn-97-Gly-98 sequence (domain III) is the greatest contributor
      to isoaspartate formation. Other major sites of isoaspartate formation are Asp
      131-Gly-132 and Asp-133-Gly-134 in domain IV, and Asn-60-Gly-61 in domain II.
      Significant isoaspartate formation was also localized to Asp-20, Asp-22, and/or
      Asp-24 in domain I, to Asp-56 and/or Asp-58 in domain II, and to Asp-93 and/or
      Asp-95 in domain III. All of these residues are calcium ligands in the highly
      conserved EF-hand calcium-binding motif. Thus, other EF-hand proteins may also be
      subject to isoaspartate formation at these ligands. The results support the idea
      that isoaspartate formation in structured proteins is strongly influenced by both
      the C-flanking residue and by local flexibility.

PMID- 8251941
TI  - Sites of iodination in recombinant human brain-derived neurotrophic factor and
      its effect on neurotrophic activity.
AB  - Recombinant human brain-derived neurotrophic factor (BDNF) is now under extensive
      investigation because of its potential clinical applications. Radioactively
      labeled proteins are usually required to study receptor binding and
      pharmacokinetic properties of proteins. This study was undertaken to see if
      iodination affects the biological and conformational properties of a recombinant
      BDNF. BDNF was iodinated using a stoichiometric amount of nonradioactive cold NaI
      to minimize multiple iodinations. Of the four tyrosines present in BDNF--Tyr-52,
      Tyr-54, Tyr-63, and Tyr-86--only Tyr-63 and Tyr-86 were iodinated under the
      experimental conditions used. Iodination of Tyr-63 resulted in modification
      without alteration of the biological activity, whereas iodination of Tyr-86
      resulted in a molecule with highly compromised biological activity. Similar
      inactivation was observed if both Tyr-63 and Tyr-86 were iodinated. These
      modified proteins exhibited conformation and dimerization apparently identical to
      those of the native protein, as demonstrated by analytical ultracentrifugation,
      gel filtration, light scattering, and circular dichroism. From these results, we
      concluded that Tyr-52 and Tyr-54 are not accessible to the reagent and are
      probably buried in the hydrophobic core, whereas Tyr-63 and Tyr-86 are exposed on
      the surface of the molecule; of the two exposed residues, only Tyr-86 contributes
      to the biological activity.

PMID- 8251942
TI  - A structural model for the nucleotide binding domains of the flavocytochrome b
      245 beta-chain.
AB  - NADPH is a system in phagocytic cells that generates O2- and hydrogen peroxide in
      the endocytic vacuole, both of which are important for killing of the engulfed
      microbe. Dysfunction of this oxidase results in the syndrome of chronic
      granulomatous disease, characterized by a profound predisposition to bacterial
      and fungal infections. A flavocytochrome b is the site of most of the mutations
      causing this syndrome. The FAD and NADPH binding sites have been located on the
      beta subunit of this molecule, the C-terminal half of which showed weak sequence
      similarity to other reductases, including the ferredoxin-NADP reductase (FNR) of
      known structure. This enabled us to build a model of the nucleotide binding
      domains of the flavocytochrome using this structure as a template. The model was
      built initially using a novel automatic modeling method based on distance-matrix
      projection and then refined using energy minimization with appropriate side-chain
      torsional constraints. The resulting model rationalized much of the observed
      sequence conservation and identified a large insertion as a potential regulatory
      domain. It confirms the inclusion of the neutrophil flavocytochrome b-245 (Cb
      245) as a member of the FNR family of reductases and strongly supports its
      function as the proximal electron transporting component of the NADPH oxidase.

PMID- 8251943
TI  - Confidence limits on the branching order of phylogenetic trees.
AB  - We describe a confidence test for branching order that can aid protein phylogeny
      reconstruction as well as the evaluation of the optimal tree. It is proposed that
      the process resulting in the observed amino acid residue differences, which is
      the basis for the identification of the order and relative times of divergence
      events, is appropriately described by a modification of the negative binomial
      distribution. The relative total numbers of mutations (accepted and nonaccepted),
      which result in a given number of amino acid differences, may be obtained as the
      expectation of this distribution. The associated variances enable significant
      differences in tree branching order to be established. If the total rates of
      mutation of the genes encoding the compared proteins are equal, the expected
      total mutations and their associated variances map identically to their relative
      times of divergence. In addition, significantly different rates of change (due to
      differences in total mutation rate and/or acceptance rate) may be identified
      without the requirement of outlying reference group. The method is equally
      applicable to phylogenies derived from DNA or RNA sequence information.

PMID- 8251944
TI  - Prediction of protein conformation on the basis of a search for compact
      structures: test on avian pancreatic polypeptide.
AB  - Based on the concept that hydrophobic interactions cause a polypeptide chain to
      adopt a compact structure, a method is proposed to predict the structure of a
      protein. The procedure is carried out in four stages: (1) use of a virtual-bond
      united-residue approximation with the side chains represented by spheres to
      search conformational space extensively using specially designed interactions to
      lead to a collapsed structure, (2) conversion of the lowest-energy virtual-bond
      united-residue chain to one with a real polypeptide backbone, with optimization
      of the hydrogen-bond network among the backbone groups, (3) perturbation of the
      latter structure by the electrostatically driven Monte Carlo (EDMC) procedure,
      and (4) conversion of the spherical representation of the side chains to real
      groups and perturbation of the whole molecule by the EDMC procedure using the
      empirical conformational energy program for peptides (ECEPP/2) energy function
      plus hydration. Application of this procedure to the 36-residue avian pancreatic
      polypeptide led to a structure that resembled the one determined by X-ray
      crystallography; it had an alpha-helix starting at residue 13, with the N
      terminal portion of the chain in an extended conformation packed against the
      alpha-helix. Similar structures with slightly higher energies, but looser
      packing, were also obtained.

PMID- 8251945
TI  - Disulfide structures of highly bridged peptides: a new strategy for analysis.
AB  - A new approach is described for analyzing disulfide linkage patterns in peptides
      containing tightly clustered cystines. Such peptides are very difficult to
      analyze with traditional strategies, which require that the peptide chain be
      split between close or adjacent Cys residues. The water-soluble tris-(2
      carboxyethyl)-phosphine (TCEP) reduced disulfides at pH 3, and partially reduced
      peptides were purified by high performance liquid chromatography with minimal
      thiol-disulfide exchange. Alkylation of free thiols, followed by sequencer
      analysis, provided explicit assignment of disulfides that had been reduced. Thiol
      disulfide exchange occurred during alkylation of some peptides, but correct
      deductions were still possible. Alkylation competed best with exchange when
      peptide solution was added with rapid mixing to 2.2 M iodoacetamide. Variants
      were developed in which up to three alkylating agents were used to label
      different pairs of thiols, allowing a full assignment in one sequencer analysis.
      Model peptides used included insulin (three bridges, intra- and interchain
      disulfides; -Cys.Cys- pair), endothelin and apamin (two disulfides; -Cys.x.Cys-
      pair), conotoxin GI and isomers (two disulfides; -Cys.Cys- pair), and bacterial
      enterotoxin (three bridges within 13 residues; two -Cys.Cys- pairs). With
      insulin, all intermediates in the reduction pathway were identified; with
      conotoxin GI, analysis was carried out successfully for all three disulfide
      isomers. In addition to these known structures, the method has been applied
      successfully to the analysis of several previously unsolved structures of similar
      complexity. Rates of reduction of disulfide bonds varied widely, but most
      peptides did not show a strongly preferred route for reduction.

PMID- 8251946
TI  - Echistatin disulfide bridges: selective reduction and linkage assignment.
AB  - Echistatin is the smallest member of the disintegrin family of snake venom
      proteins, containing four disulfides in a peptide chain of 49 residues. Partial
      assignment of disulfides has been made previously by NMR and chemical approaches.
      A full assignment was made by a newly developed chemical approach, using partial
      reduction with tris-(2-carboxyethyl)-phosphine at acid pH. Reduction proceeded in
      a stepwise manner at pH 3, and the intermediates were isolated by high
      performance liquid chromatography. Alkylation of free thiols, followed by
      sequencer analysis, enabled all four bridges to be identified: (1) at 20 degrees
      C a single bridge linking Cys 2-Cys 11 was broken, giving a relatively stable
      intermediate; (2) with further treatment at 41 degrees C the bridges Cys 7-Cys 32
      and Cys 8-Cys 37 became accessible to the reagent and were reduced at approx.
      equal rates; (3) the two bicyclic peptides produced in this manner were less
      stable and could be reduced at 20 degrees C to a peptide that retains a single
      bridge linking Cys 20-Cys 39; and (4) the monocyclic peptide can be reduced to
      the linear molecule at 20 degrees C. Some disulfide exchange occurred during
      alkylation of the bicyclic intermediates, but results unambiguously show the
      pattern to be [2-11; 7-32; 8-37; 20-39]. A comparison is made with kistrin, a
      longer disintegrin whose disulfide structure has been proposed from NMR analysis.

PMID- 8251947
TI  - Identification of cysteine ligands in metalloproteins using optical and NMR
      spectroscopy: cadmium-substituted rubredoxin as a model [Cd(CysS)4]2- center.
AB  - Optical and NMR methods are presented for the identification of cysteine ligands
      in Cd-substituted metalloproteins, in particular those containing zinc-fingerlike
      motifs, using Cd-substituted Desulfovibrio gigas rubredoxin (Cd-Rd) as a model
      [Cd(CysS)4]2- complex. The 113Cd NMR spectrum of Cd-Rd contains a single 113Cd
      resonance with a chemical shift position (723.6 ppm) consistent with
      tetrathiolate metal coordination. The proton chemical shifts of the four cysteine
      ligands were obtained from one-dimensional heteronuclear (1H-113Cd) multiple
      quantum coherence (HMQC) and total coherence spectroscopy (TOCSY)-relayed HMQC
      experiments. In addition, sequential assignments were made for two short cysteine
      containing stretches of the polypeptide chain using a combination of homonuclear
      proton correlated spectroscopy, TOCSY, and nuclear Overhauser effect spectroscopy
      experiments, enabling sequence-specific heteronuclear 3J(1H beta-113Cd) coupling
      constants for each cysteine to be determined. The magnitude of these couplings (0
      38 Hz) follows a Karplus-like dependence with respect to the H beta-C beta-S
      gamma-Cd dihedral angles, inferred from the crystal structure of the native
      protein. The difference absorption envelope (Cd-Rd vs. apo-Rd) reveals three
      distinct transitions with Gaussian-resolved maxima located at 213, 229, and 245
      nm, which are paralleled by dichroic features in the corresponding difference CD
      and magnetic CD spectra. Based on the optical electronegativity theory of
      Jorgensen, the lowest energy transition has been attributed to a CysS-Cd(II)
      charge-transfer excitation (epsilon 245, 26,000 M-1 cm-1) with a molar extinction
      coefficient per cysteine of 6,500 M-1 cm-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8251948
TI  - Identification of a common protease-sensitive region in D-alanyl-D-alanine and D
      alanyl-D-lactate ligases and photoaffinity labeling with 8-azido ATP.

PMID- 8251949
TI  - Crystallization and preliminary crystallographic study of an Fab fragment of a
      pathogenic rat monoclonal antibody against the nicotinic acetylcholine receptor.

PMID- 8251950
TI  - 1994 Stein and Moore Award.

PMID- 8251951
TI  - ATP-stimulated translocation promoter that enhances the nuclear binding of
      activated glucocorticoid receptor complex. Biochemical properties and its
      function (mini-review).
AB  - Association of nonhormone binding proteins with steroid receptor protein as well
      as modifications of the receptor by ATP, PPi, pyridoxal 5'-phosphate, molybdate,
      and the large number of less-well-characterized factors are important for the
      modulation and control of signal transduction in the steroid-receptor systems.
      Each of the steps in the steroid-receptor system, that is, the steroid binding,
      nuclear binding, DNA binding, and transcriptional regulations of specific genes
      (glucocorticoid response elements; GREs), may be controlled by the receptor
      interactions with other proteins and modulators. During the study on the
      regulatory mechanism of glucocorticoid-receptor system, we found a new endogenous
      factor in rat liver cytosol that increases the binding of activated
      glucocorticoid-receptor complex (GRC) to nuclei in the presence of ATP, and we
      named this factor ATP-stimulated translocation promoter (ASTP). Recently, we have
      purified ASTP protein to homogeneity and characterized it. ASTP has an M(r) of
      93,000, and is composed of two apparently identical subunits with M(r) of 48,000.
      The sedimentation coefficient of ASTP is 6.5S, and its isoelectric point is 4.5.
      ASTP increases the binding of activated GRC to nuclei and chromatin, but not to
      DNA. ASTP activity is dependent on the physiological concentration of ATP,
      although ASTP does not bind to ATP-agarose. Interestingly, ASTP can bind to the
      arginine-rich histones H3 and H4, to which activated GRC also binds. In this
      article, we will summarize the biochemical properties of this interesting protein
      (ASTP) and will discuss our thinking about the mode of action.

PMID- 8251952
TI  - Estrogen receptor-dependent formation of two distinct multiprotein complexes on
      the human pS2 gene regulatory segment. Participation of a c-fos related protein.
AB  - DNA-protein interactions around the regulatory region of the pS2 gene were
      studied to gain insight into the mechanisms that operate in the estrogen receptor
      regulated expression of this gene in the MCF-7 human breast cancer cell. Using a
      revised photocrosslinking technology in combination with gel retardation assays,
      two distinct multiprotein DNA complexes were shown to assemble in an estrogen
      receptor-dependent process. Immunological analysis demonstrated the participation
      of both the estrogen receptor and a c-fos related protein in the formation of
      these complexes. The results support a model of estrogen receptor function in
      which the receptor facilitates the formation of multiprotein complexes at DNA
      sites that can regulate the transcription of a hormone responsive gene by RNA
      polymerase II and any additional general transcription machinery. These receptor
      containing complexes are referred to as "receptorsomes."

PMID- 8251953
TI  - Characterization of defective phorbol ester responses in a low secreting rat
      basophilic leukemia (RBL-2H3) cell variant.
AB  - The role of protein kinase C (PKC) in the signaling mechanism that stimulates the
      release of mediators from rat mast cells, for which the RBL-2H3 cell line is a
      model, is at present unresolved. Current evidence suggests that PKC activation
      alone is an insufficient stimulus, although it can modulate mast cell exocytosis
      induced by other agents. In this article we characterize a variant of the RBL-2H3
      cell line that has a reduced capacity for mediator secretion in response to an
      IgE-mediated antigen-induced stimulation. The outcome of our study suggests that
      at least two PKC isotypes are active in RBL-2H3 cells, and affect the positive
      and negative modulation of the secretory response.

PMID- 8251954
TI  - Use of radioreceptor assay and cell superfusion system for in vitro screening of
      analogs of growth hormone-releasing hormone.
AB  - In the search for more active agonists and antagonists of human growth hormone
      releasing hormone (hGH-RH), various analogs are being synthesized. In order to
      follow the binding affinity of these analogs, we have developed a sensitive in
      vitro radioreceptor assay for GH-RH based on binding of labeled [His1,Nle27]hGH
      RH(1-32)NH2 to rat anterior pituitary membrane homogenates by adapting and
      modifying earlier methods. Scatchard analysis of saturation binding data
      demonstrated the presence of a single class of specific binding sites for GH-RH
      in membranes of rat anterior pituitaries with a Bmax of 33.3 +/- 5.2 fmol/mg
      protein and an apparent Kd of 0.19 +/- 0.02 nM. In displacement analyses, we
      compared the binding affinity of [His1,Nle27]hGH-RH(1-32)NH2 with its iodinated
      derivative. No significant differences were detected in IC50 concentrations
      ranging from 0.97 to 3.4 nM between labeled and nonlabeled hGH-RH analogs. These
      findings demonstrate the validity of the radioreceptor assay. To evaluate the
      biological activities of hGH-RH derivatives, we applied a sensitive, dispersed
      rat pituitary cell superfusion system. This dynamic in vitro system eliminates
      the drawbacks of the static pituitary cell culture. No differences were observed
      in biological activities of the iodinated and noniodinated hGH-RH analogs. GH
      releasing activity obtained from the superfusion assay correlated well with GH-RH
      receptor binding affinity for all nonlabeled and labeled hGH-RH analogs examined.
      These two methods are fast, simple, and relatively inexpensive, and provide
      quantitative data on receptor affinities, biological activities, and hence
      structure-affinity and structure-activity relationships. Joint use of these two
      in vitro systems appears to be suitable for screening newly synthesized GH-RH
      analogs.

PMID- 8251955
TI  - Characterization of the human oxysterol receptor overexpressed in the baculovirus
      system.
AB  - Oxysterols are potent regulators of enzymes of the de novo cholesterol
      biosynthetic pathway and do not require the LDL (low density lipoprotein):LDL
      receptor system for their regulatory actions. The search for an alternate
      transduction system led to the identification of an oxysterol binding protein.
      This cytosolic protein has been extensively characterized, purified, and cloned.
      Although it fulfills the pharmacologic criteria for an oxysterol receptor by
      binding to oxysterols with affinities corresponding to their regulatory
      potencies, its function in maintaining cholesterol homeostasis has not been
      determined. We have overexpressed the human oxysterol receptor in Spodoptera
      frugiperda cells using the Baculovirus system. The overexpressed protein binds
      oxysterols, but not cholesterol. The affinity for 25-hydroxycholesterol
      determined by competitive binding assay was 7.3 +/- 4.4 nM (mean +/- SD), and the
      relative affinities of several other oxysterols approximately corresponded to
      their potencies in cell systems. The expressed protein migrated as a single
      immunoreactive band on denaturing polyacrylamide gels with a molecular mass of 94
      kDa. The molecular mass calculated from sucrose gradient centrifugation and gel
      filtration was 273 kDa for the 9.8S form, 217 kDa for the 7.8S form, and 184 kDa
      for the 6.6S form. However, velocity gradient centrifugation and heparin
      sepharose chromatography each indicated that there were at least two fractions
      containing specific oxysterol binding. We conclude that we have successfully
      overexpressed the human oxysterol receptor and that biochemical analysis of the
      overexpressed protein provides evidence of interactions with other proteins.
      Further analysis of the overexpressed protein should provide clues regarding its
      role in maintaining cholesterol homeostasis.

PMID- 8251956
TI  - Primary hypothyroidism: a case for vigilance in the psychological treatment of
      depression.
AB  - Primary hypothyroidism is a relatively common endocrine disorder that develops
      insidiously and can mimic depression. Between 8 and 14 per cent of patients
      diagnosed as depressed may have some degree of hypothyroidism. It is recommended
      that clinical psychologists equip themselves with sufficient knowledge to
      recognize the disorder. Primary hypothyroidism is described with respect to its
      causes, course, investigation and treatment. Suggestions are made to help
      psychologists determine whether a medical referral is appropriate.

PMID- 8251957
TI  - Psychosocial aspects of sickle cell disease (SCD) in childhood and adolescence: a
      review.
AB  - This paper reviews the literature on the psychological and social aspects of
      Sickle Cell Disease (SCD) and discusses the clinical implications of its impact
      on children and their families. Sickle Cell Disease is a family of blood diseases
      including sickle cell anaemia (SS), SC disease (SC), and sickle B thalassaemia
      (SBThal). Research on the psychological and social aspects of SCD, particularly
      in the UK, has been limited and of varying methodological quality. The
      psychosocial adaptation of children and adolescents with SCD and their families
      has been associated with the personality and developmental stage of the child,
      family attitudes and behaviour, socioeconomic status, and social and
      environmental support. Concerns about the quality of interpersonal relationships
      within families have also led to investigations of family characteristics and
      social networks, and some research studies have pointed to different ways of
      coping associated with specific network and family structures.

PMID- 8251958
TI  - You in Mind: a preventive mental health television series.
AB  - This study of BBC Television's 'You in Mind' series provides preliminary evidence
      for the benefits of a mass media approach to preventive mental health. The series
      was seen by a large national audience who appraised it positively. It had a
      greater impact in the area of understanding problems as opposed to seeing what to
      do about them, and a greater impact on the viewer's perceptions of the problems
      of people the viewers knew, as opposed to the problems of the viewers themselves.
      Measures of intentions to change behaviour, even when corrected for over
      reporting, suggest that a significant minority of the audience had changed or
      intended to change their behaviour as a result of the series. However, no
      specific pre-post changes in coping or help-seeking were found. These findings
      are discussed in terms of the potential and limitations of the mass media for
      mental health promotion.

PMID- 8251959
TI  - Interrogative suggestibility, confabulation, and acquiescence in people with mild
      learning disabilities (mental handicap): implications for reliability during
      police interrogations.
AB  - In order to assess a criminal suspect's ability to make a reliable statement,
      performance on three measures--interrogative suggestibility, confabulation and
      acquiescence--may be used. This paper presents preliminary data on these measures
      for people with mild learning disabilities (Full Scale IQ [FSIQ]: 57-75). It was
      found that they were more suggestible than their average ability counterparts
      (FSIQ: 83-111) because they were much more susceptible to 'leading questions'.
      They also confabulated more and were more acquiescent. Overall, the data
      emphasized their potential vulnerability to giving erroneous testimony during
      interrogations.

PMID- 8251960
TI  - Preliminary evaluation of a Low-Cost VideoConferencing (LCVC) system for remote
      cognitive testing of adult psychiatric patients.
AB  - Mini-Mental State Examination scores were compared in an adult psychiatric
      population when the test was performed face to face and over a Low-Cost
      VideoConferencing System (LCVC). The minor changes to the instrument that are
      required to make it compatible with the LCVC are described. The high correlations
      achieved between the test scores in the two conditions suggests that this
      cognitive screening test may be reliably performed in this group of patients over
      the LCVC.

PMID- 8251961
TI  - First impressions count: a controlled investigation of social skill following
      closed head injury.
AB  - This study examined social skills in 14 closed head injured (CHI) patients who
      were assessed at four months post-injury and compared with 19 orthopaedic control
      (OC) patients. Social skills deficits were found to be more common in the CHI
      patients, of whom over half were classified as socially unskilled. CHI patients
      displayed poorer social skills in the earlier (but not later) part of an extended
      social interaction, indicating that they make a poor first impression. It is
      suggested that poor initial impression formation skills may be one reason why CHI
      patients fail to establish and maintain friendships. Implications of these
      findings for patient management are discussed. Close others of CHI patients
      reported higher levels of mood disturbance. Higher levels of close other
      hostility were associated with social skills deficits in CHI patients.

PMID- 8251962
TI  - Effect of rational and irrational statements on intensity and 'inappropriateness'
      of emotional distress and irrational beliefs in psychotherapy patients.
AB  - Ellis's rational-emotive theory postulates that since irrational statements
      augment emotional distress, replacing irrational with rational statements should
      lessen distress. This hypothesis was tested in the initial stages of
      psychotherapy by having 13 and 14 clinical out-patients respectively repeat for
      one minute either rational or irrational statements about their major presenting
      psychological problem. The distinction by Ellis & Harper (1975) that
      'inappropriate' emotions differ qualitatively from 'appropriate' emotions was
      also examined. Although the experimental intervention had no effect on a post
      test measure of irrational beliefs, patients repeating rational statements had
      significantly lower appropriate and inappropriate negative emotions at post-test,
      suggesting that inappropriate emotions do not differ qualitatively from
      appropriate emotions and that making rational statements may lower emotional
      distress in patients. Patients reiterating irrational statements showed no change
      in emotions, implying that these kinds of irrational cognitions may have already
      been present.

PMID- 8251963
TI  - The Herald of Free Enterprise disaster: measuring post-traumatic symptoms 30
      months on.
AB  - The aim of the present study was to explore the psychometric properties of the
      Impact of Events Scale. Evidence is presented that the scale is composed of two
      major factors tapping intrusion and avoidance which are associated with greater
      psychological distress.

PMID- 8251964
TI  - Utility of the Modified Wisconsin Card Sorting Test in neuropsychological
      assessment.
AB  - Nelson's (1976) Modified Wisconsin Card Sorting Test (MCST) was evaluated and the
      utility of the conventional criterion and new threshold scores for identifying
      patients with frontal lobe disorder assessed. Measures of perseveration and other
      indices of performance on the MCST were not found to discriminate between
      patients with frontal and non-frontal lobe lesions, using either the conventional
      criterion or new threshold scores. In addition there were no significant
      differences between left- and right-sided lesioned patients. However, the task
      was found to have high specificity (98.7 per cent) and good sensitivity (45.6 per
      cent) to lesions irrespective of site indicating that it may be a useful
      screening test. The present findings are consistent with recent research with the
      original Wisconsin Test, that suggests that card-sorting performance may not be
      as differentially sensitive to frontal lobe disorder as has been thought
      hitherto.

PMID- 8251965
TI  - Sequential Cotard and Capgras delusions.
AB  - We report sequential Cotard and Capgras delusions in the same patient, KH, and
      offer a simple hypothesis to account for this link. The Cotard delusion occurred
      when KH was depressed and the Capgras delusion arose in the context of
      persecutory delusions. We suggest that the Cotard and Capgras delusions reflect
      different interpretations of similar anomalous experiences, and that the
      persecutory delusions and suspiciousness that are often noted in Capgras cases
      contribute to the patients' mistaking a change in themselves for a change in
      others ('they are impostors'), whereas people who are depressed exaggerate the
      negative effects of the same change whilst correctly attributing it to themselves
      ('I am dead'). This explains why there might be an underlying similarity between
      delusions which are phenomenally distinct.

PMID- 8251966
TI  - Sexual abuse and body-image distortion in the eating disorders.
AB  - It has been suggested that there is a link between sexual abuse and bodily self
      deprecation in women with eating disorders. In order to test that model, this
      study considers whether reported sexual abuse is associated with body-image
      distortion in anorexia and bulimia nervosa. There was no association with the
      reported presence of a history of abuse. However, the nature of any abuse was
      important. In particular, women who reported more recent abuse had a
      substantially greater level of bodysize overestimation. The clinical implications
      of this finding are discussed.

PMID- 8251967
TI  - Proactive interference and the neuropsychology of schizophrenia.
AB  - Gray, Felden, Rawlins, Hemsley & Smith (1991) have proposed a theoretical model
      of the neuropsychology of schizophrenia. A major feature of this model is that it
      is a weakening of the influences of memories of previous input on current
      perception/learning which is basic to the phenomenon of acute schizophrenia. In
      the present study, proactive interference (PI) was used as a paradigm to test
      this hypothesis. PI occurs when new learning is diminished as a consequence of
      previously learned material. According to our reading of the Gray et al. (1991)
      model, acutely ill unmedicated patients with schizophrenia should demonstrate
      reduced PI relative to controls. Ten acutely ill unmedicated patients with
      schizophrenia, 20 patients suffering from major depressive disorder, and 20
      healthy controls were assessed using a PI paradigm. No significant differences in
      PI emerged between the groups. The results do not support this specific feature
      of the neuropsychological model of acute schizophrenia proposed by Gray et al.
      (1991).

PMID- 8251968
TI  - Quality of attention in chronic fatigue syndrome: subjective reports of everyday
      attention and cognitive difficulty, and performance on tasks of focused
      attention.
AB  - Patients with chronic fatigue syndrome (also known as post-viral fatigue syndrome
      or myalgic encephalomyelitis) commonly report cognitive difficulties concerning
      attention, concentration and memory. In this study, patients were compared with
      matched controls on two questionnaires which assess subjective difficulties with
      attention and general cognitive functioning, and on two tasks requiring focused
      attention. Patients reported significantly greater difficulty with attention on
      the Everyday Attention Questionnaire and more cognitive symptoms on the Profile
      of Fatigue-Related Symptoms. The objective tests did not clearly indicate a
      deficit in patients' focused attention; patients tended to perform less well on
      the Embedded Figures Test and the Stroop Colour-Word Interference Test, but these
      differences were not significant. There was, however, evidence of psychomotor
      retardation, with patients having longer response times for word reading and
      colour naming in the Stroop test. Difficulties in interpreting findings for both
      subjective and objective cognitive measures are discussed.

PMID- 8251969
TI  - Self-referential selective memory in pain patients.
AB  - The effect of self-reference on recall bias for pain stimuli was compared in
      chronic pain patients and controls. It was hypothesized that self-referential
      encoding would result in better recall of pain stimuli in chronic pain patients.
      In contrast, it was predicted that a non-pain control group would display no
      recall bias for pain-associated stimuli, regardless of the encoding reference.
      Subjects were tested in two conditions. The first condition (self-referential)
      involved encoding a list of words constructed from sensory pain, affective and
      neutral words. Elaboration at the encoding stage was achieved by asking subjects
      to imagine themselves in situations involving these words. Subjects were also
      asked to rate the likelihood of these situations occurring on a scale of 1 to 5
      (from 1 = 'will not happen' to 5 = 'certain to happen'). The second condition
      (other-person reference) repeated this task in reference to another person with a
      matched list of words. A 2 x 2 x 3 factorial analysis of variance based on group
      x reference (self and other) x word type (sensory, affective and neutral) was
      carried out on recall scores, with the likelihood ratings as a covariate. Results
      reveal a significant three-way interaction. The analysis indicated that, while
      pain patients show an increase in recall of sensory words and a decrease in
      recall of neutral words when these are encoded in reference to themselves,
      control subjects show no difference in recall of these word types regardless of
      the encoding condition. The results support the notion that pain patients
      selectively recall more pain-associated words in comparison with other word
      types. However, this effect is only true for stimuli encoded in reference to
      themselves. It is proposed that this processing bias may contribute to the
      maintenance of a sense of helplessness and exacerbate the emotional impact of the
      pain experience.

PMID- 8251970
TI  - Recent health sciences library building projects.
AB  - The Medical Library Association's third annual survey of recent health sciences
      library building projects identified fourteen libraries planning, expanding, or
      constructing new library facilities. Three of five new library buildings are
      freestanding structures where the library occupies all or a major portion of the
      space. The two other new facilities are for separately administered units where
      the library is a major tenant. Nine projects involve additions to or renovations
      of existing space. Six projects are in projected, predesign, or design stages or
      are awaiting funding approval. This paper describes four projects that illustrate
      technology's growing effect on librarians and libraries. They are designed to
      accommodate change, a plethora of electronic gear, and easy use of technology.
      Outwardly, they do not look much different than many other modern buildings. But,
      inside, the changes have been dramatic although they have evolved slowly as the
      building structure has been adapted to new conditions.

PMID- 8251971
TI  - Accuracy of indexing coverage information as reported by serials sources.
AB  - This article reports on the accuracy of indexing service coverage information
      listed in three serials sources: Ulrich's International Periodicals Directory,
      SERLINE, and The Serials Directory. The titles studied were randomly selected
      journals that began publication in either 1981 or 1986. Aggregate results reveal
      that these serials sources perform at 92%, 97%, and 95% levels of accuracy
      respectively. When the results are analyzed by specific indexing services by
      year, the performance scores ranged from 80% to 100%. All three serials sources
      tend to underreport index coverage. The author advances five recommendations for
      improving index coverage accuracy and four specific proposals for future
      research. The results suggest that, for the immediate future, librarians should
      treat index coverage information reported in these three serials sources with
      some skepticism.

PMID- 8251972
TI  - The Houston Academy of Medicine--Texas Medical Center Library management
      information system.
AB  - A management information system (MIS) provides a means for collecting, reporting,
      and analyzing data from all segments of an organization. Such systems are common
      in business but rare in libraries. The Houston Academy of Medicine-Texas Medical
      Center Library developed an MIS that operates on a system of networked IBM PCs
      and Paradox, a commercial database software package. The data collected in the
      system include monthly reports, client profile information, and data collected at
      the time of service requests. The MIS assists with enforcement of library
      policies, ensures that correct information is recorded, and provides reports for
      library managers. It also can be used to help answer a variety of ad hoc
      questions. Future plans call for the development of an MIS that could be adapted
      to other libraries' needs, and a decision-support interface that would facilitate
      access to the data contained in the MIS databases.

PMID- 8251974
TI  - Information-seeking behavior: a survey of health sciences faculty use of indexes
      and databases.
AB  - This study investigated information-seeking behavior, including use of major
      bibliographic tools by medical, pharmacy, nursing, and science faculty at the
      University of Illinois at Chicago. The study assessed the impact of availability
      of locally mounted databases, determined needs for modification of instructional
      programs, identified the need for promotional material, and established a
      baseline for subsequent studies. Results reflected a wide variation in the number
      and format of secondary services used by faculty. Over 70% of all faculty from
      the colleges of medicine, pharmacy, and nursing used Index Medicus or MEDLINE.
      There were statistically significant differences between colleges in their use of
      mediated and end-user searching of MEDLINE. Colleges exhibited significant
      differences in use of Current Contents, PsycLIT, ERIC, Cumulative Index to
      Nursing and Allied Health Literature (CINAHL), Chemical Abstracts, and Science
      Citation Index. Statistically significant differences also were found among
      several clinical departments. The study concluded that, as new formats to
      bibliographic tools become available, traditional formats continue to be used;
      training sessions must be tailored to the audience; and the availability of local
      resources and their use by faculty needs to be understood.

PMID- 8251973
TI  - Rural GRATEFUL MED outreach: project results, impact, and future needs.
AB  - The Library of the Health Sciences-Peoria (LHS-Peoria), located at a regional
      site of the University of Illinois College of Medicine, conducted an eighteen
      month GRATEFUL MED outreach project funded by the National Library of Medicine.
      The project was designed to enhance information services for health professionals
      at eight underserved rural hospitals in west central Illinois. One hundred rural
      health professionals, mainly nonphysicians, received GRATEFUL MED training at
      these hospitals; LHS delivered more than 350 documents to the trainees. In this
      paper, investigators describe the project and its goals and discuss results and
      their evaluation, from both individual and institutional perspectives. Outcome is
      examined in the context of future outreach plans, both at LHS and elsewhere.

PMID- 8251975
TI  - Surveying knowledge and skills in the health sciences: results and implications.
AB  - The MLA Knowledge and Skills Task Force was appointed in May 1989. The task force
      decided to survey a sample of the membership to define the knowledge and skills
      required for competent professional performance and to enable MLA to establish
      educational policies which would ensure acquisition and maintenance of the
      necessary knowledge and skills throughout a professional career. This report
      presents the initial findings of the survey, upon which MLA's educational policy
      statement, Platform for Change, is based.

PMID- 8251976
TI  - Impact of information technology on the role of health sciences librarians.
AB  - Information technology is transforming the nature of health sciences information
      and its management, thereby altering the traditional responsibilities of health
      sciences librarians. As a result, the traditional educational preparation for
      librarianship is no longer entirely relevant, and there is a real possibility
      that information management will be taken over by individuals with different
      educational backgrounds and skills. This paper explores four topics relevant to
      this issue: the emergence of new forms of health sciences information, the impact
      of technology on the practice of health sciences librarianship, the interaction
      of technology and the practice of health sciences librarianship, and the
      relationship among these three topics and the educational preparation of health
      sciences librarians.

PMID- 8251977
TI  - The health information environment: a view of organizational and professional
      needs and priorities.
AB  - Inspired by Platform for Change: The Educational Policy Statement of the Medical
      Library Association, this paper discusses the institutional changes, new delivery
      modes and services, learning and development, leadership, and strategies needed
      for health sciences librarians to prosper in the changing medical information
      environment. To fulfill their potential, librarians must articulate and act upon
      a vision that involves them more fully in the work of faculty, researchers, and
      medical practitioners.

PMID- 8251978
TI  - Charting a path for health sciences librarians in an integrated information
      environment.
AB  - Changes in the health information environment present a major challenge to health
      sciences librarians. To successfully meet this challenge, librarians must apply
      the concepts of informal, self-directed, lifelong learning to their own carers.
      The Joint Commission on Accreditation of Healthcare Organizations is creating an
      integrated information environment in health care organizations. The health
      sciences librarian brings unique knowledge and skills to this environment. The
      reference technique, a methodology that closely parallels other problem-solving
      approaches such as the physician's diagnostic technique, equips librarians with
      the conceptual skills to develop creative solutions to information management
      problems. Each health sciences librarian must assume responsibility for extending
      professional skills and abilities and demonstrating them in the workplace.

PMID- 8251979
TI  - Beyond the classroom: self-direction in professional learning.
AB  - Against the backdrop of a rapidly changing profession, the context for
      professional thinking among medical librarians is changing. Competent performance
      increasingly is linked with the educational efforts of self-directed adult
      learners. This paper examines strategies that facilitate self-direction,
      including skills development, organizational learning, learner-based decision
      making, and alternative teaching models. The analysis provides the basis for a
      recommended agenda for redesign and development of educational programs.

PMID- 8251980
TI  - Assessing nurses' information needs in the work environment.

PMID- 8251981
TI  - Funding a patient education collection.

PMID- 8251982
TI  - Continuous quality improvement in the hospital library.

PMID- 8251983
TI  - End-user errors: a content analysis of PaperChase transaction logs.

PMID- 8251984
TI  - A decade of AIDS literature: author response.

PMID- 8251985
TI  - MLA headquarters and copyright.

PMID- 8251986
TI  - Thomas P. Fleming, 1907-1992.

PMID- 8251987
TI  - Elliott How Morse, 1916-1992.

PMID- 8251989
TI  - Expanded programme on immunization. Global review of missed opportunities for
      immunization.

PMID- 8251988
TI  - National Advisory Committee on Immunization (NACI). Statement on Japanese
      encephalitis vaccine.

PMID- 8251990
TI  - Operative intervention for plantar calcaneal pain represents a controversial
      subject among surgeons.

PMID- 8251992
TI  - Totally implanted direct current stimulator as treatment for a nonunion in the
      foot.
AB  - Nonunions and delayed unions are postoperative complications with which the
      podiatric surgeon must be concerned. Although the incidence is infrequent, their
      treatment methods vary, and can range from bone grafting to internal and external
      fixation of fragments, arthrodesis, and/or the use of indirect and direct bone
      stimulation. This manuscript details a case of a nonunion of the first metatarsal
      cuneiform joint 8 months after attempted Lisfranc's joint fusion for Charcot
      arthropathy of the midfoot. The nonunion was treated with bone grafting, internal
      fixation, and the use of an implanted direct current bone stimulator. Although
      implanted bone stimulators are commonly used for the treatment of failed unions
      of the posterior spine, tibia, and humerus, to date, the authors submit this is
      the first reported case of implementing a totally implanted direct current
      stimulator for treatment of a nonunion in the foot.

PMID- 8251991
TI  - Trans-chondral fractures of the talus: a review of 64 surgical cases.
AB  - The authors present a retrospective study of 67 transchondral fractures of the
      talus in 64 patients that were treated surgically. A thorough literature review,
      physiology of articular cartilage and subchondral bone repair, and a
      comprehensive treatment of transchondral lesions are presented. Consideration is
      given to surgical approaches that require fibular and medial malleolar osteotomy,
      and to open reduction with internal fixation of the transchondral fractures. A
      new, practical, radiographic classification with appropriate terminology is
      proposed which acknowledges recent fractures from subsequent avascular necrosis
      of the lesions.

PMID- 8251993
TI  - Chevron closing base wedge bunionectomy.
AB  - The Chevron-base wedge Association for Osteosynthesis fixated bunionectomy
      provides a stable, aggressive correction of the severe hallux abducto valgus
      deformity. It is intended for the bunion requiring a double osteotomy in order to
      adequately reduce both intermetatarsal and proximal articular facet angle with
      minimal shortening and elevation. This article presents the rationale for the
      procedure, technique, and a 4-year follow-up of six patients with eight Chevron
      base wedge bunionectomies.

PMID- 8251994
TI  - Plantar fibromatosis: staging by magnetic resonance imaging.
AB  - Plantar fibromatosis is a slow growing nodular thickening that occurs most often
      within the central band of the plantar aponeurosis. Since the lesion is not
      encapsulated, clinical margins are often difficult to define. Inadequate excision
      is the primary cause of recurrence. MRI is a nonionizing radiation technique that
      demonstrates excellent definition between pathological entities and normal
      anatomy. This may aid in the preoperative planning.

PMID- 8251995
TI  - A new radiographic classification for hallux limitus.
AB  - A new classification system for hallux limitus that is based on objective
      radiographic changes around the first metatarsophalangeal joint is introduced.
      The new system is demonstrated in a 3-year, 110-patient retrospective study. From
      the information gathered, a surgical algorithm has been developed. Statistical
      analysis demonstrates an 87% satisfaction rate with the recommended surgical
      algorithm.

PMID- 8251996
TI  - Giant cell tumor of the first metatarsal bone en bloc resection with autogenous
      middle fibular strut graft.
AB  - Giant cell tumors of bone are tumors of somewhat obscure origin. Clinically, they
      often do not present until late in their development. Radiographically, they can
      appear quite aggressive. However, most are intermediate-type lesions. Curettage
      has shown a tendency toward recurrence with en bloc resection becoming more
      popular when located in a long bone. The following is a brief review and a case
      report of an aggressive giant cell tumor of the first metatarsal. An en bloc
      resection of the proximal two-thirds of the metatarsal with an autogenous middle
      fibular strut graft is presented.

PMID- 8251997
TI  - Long-term follow-up of clubfoot surgery: analysis of 44 patients.
AB  - The purpose of this study was to evaluate the long term results of clubfoot
      surgery. Forty-four patients were evaluated for periods from one to 41 years. The
      evaluation was based upon clinical, radiological and functional criteria. Results
      revealed that in spite of anatomically and radiologically imperfect feet, most
      patients demonstrated excellent levels of function. The results of other follow
      up clubfoot studies were analyzed and compared to the present study.

PMID- 8251998
TI  - Anterior process fracture of the calcaneus.
AB  - Fracture of the anterior process of the calcaneus is a common injury that is
      often misdiagnosed. The key to management of this injury is an accurate diagnosis
      and proper treatment. Two case studies are presented to demonstrate how improper
      diagnosis can lead to surgical treatment of the condition.

PMID- 8251999
TI  - Silicone implant arthroplasty: a retrospective analysis.
AB  - Fifteen patients totalling 19 first metatarsophalangeal implants were evaluated
      both subjectively and objectively. The average time of follow-up was 5.9 years.
      Sixteen implants were evaluated radiographically and the incidence of
      complications including implant deformation, bony erosions, and bony encroachment
      is reported. Postoperative clinical evaluation revealed several of the patients
      complained of pain and stiffness. Postoperative motion was restricted in most
      patients and toe purchase was present in only 6 of 16 patients. Despite the
      clinical objective findings, patient satisfaction was very favorable. Although
      the apparent complication rate appeared high, the authors recommend an effort be
      made to develop a multicentered retrospective analysis to find the true incidence
      of first metatarsophalangeal implant complications.

PMID- 8252000
TI  - Intraosseous ganglion of the cuboid bone.
AB  - Intraosseous ganglia are benign cystic lesions usually located in the end of long
      bones, especially the distal tibia. Patients typically present with mild,
      localized, aching discomfort in a joint that is aggravated by weightbearing.
      Pathogenesis is currently unknown with the literature suggesting many valid
      theories. Surgical excision and curettage is the treatment of choice. A case of a
      ganglion cyst within a cuboid bone is presented along with a review of the
      literature and discussion of operative technique.

PMID- 8252001
TI  - Angiofibroma of tendon sheath (tenosynovial fibroma) of the foot.
AB  - The author describes a rare lesion along the lateral aspect of the foot that was
      diagnosed as angiofibroma. The lesion is benign, and affects males twice as often
      as females. Its clinical and histologic appearances are illustrated.

PMID- 8252002
TI  - The Smith STA-Peg: a seven-year retrospective study.

PMID- 8252003
TI  - Technical complications of the tibiofibular syndesmotic screw.
AB  - Three patients with ankle fractures are presented to demonstrate poor results due
      to improper application of a syndesmotic screw. In these cases failure of
      surgical treatment caused accelerated disruption of the ankle mortise with
      cartilage wear, or instability and joint distraction. Simple internal fixation
      with a single screw requires strict awareness of the potential harm that can be
      inflicted on the joint. The syndesmotic screw has to be inserted with a proper
      understanding of the biomechanics of ankle joint structures.

PMID- 8252004
TI  - Digital "V" arthrodesis.
AB  - Numerous procedures have been proposed through the years for the treatment of
      digital hammertoes and other related structural deformities. Experience has
      determined that many of these procedures are structurally incorrect and result in
      secondary deformity, which are often worse than the pathology initially
      addressed. Phalangeal base resections were found to destroy the structural
      stability provided by the intrinsic musculature. Phalangeal head resections make
      the toe impressionable to the extrinsic forces of the adjacent toes often leading
      to structural mal-alignment, or additional contracture. Similarly, indiscriminate
      tendon lengthenings have led to flail toes and a lack of purchase and propulsion.
      The advent of proximal interphalangeal joint arthrodesis demonstrated that
      structural stability and propulsion could be maintained while enhancing
      alignment. The "V" arthrodesis, as introduced by the authors, provides an
      alternative surgical approach to digital fusions. This approach is technically
      less difficult compared with a peg-in-hole fusion and provides enhanced stability
      when compared with an end-to-end arthrodesis. The preliminary results of this
      procedure appear to be most promising and are provided to the readership for
      review and examination.

PMID- 8252005
TI  - Pachydermoperiostosis: a case report.
AB  - Pachydermoperiostosis in three males of seven siblings from a village of mid
      Anatolia is presented. Although X-linkage could not have been ruled out, the
      autosomal recessive inheritance was considered most likely. It differs from the
      autosomal dominant form by growth retardation, early ulcers, and acrolysis of the
      distal parts of the extremities with secondary contractures.

PMID- 8252006
TI  - Rheumatoid-like nodules presenting as Haglund's deformity in an adult,
      nonarthritic patient.
AB  - The authors present the case of an adult female patient with bilateral posterior
      heel masses. These were removed and histologically found to be rheumatoid-like
      nodules. There was no clinical or laboratory evidence of rheumatoid disease. A
      review of the literature is presented.

PMID- 8252007
TI  - A review of pyrolytic carbon: application in bone and joint surgery.
AB  - The authors review pyrolytic carbon as a biomaterial. Its potential applications
      in bone and joint surgery are discussed. This manuscript includes work performed
      in the early 1980s through present day research.

PMID- 8252008
TI  - Brachymetatarsia with the use of digital arthroplastic bone.
AB  - A review of autogenous bone graft alternatives for the correction of
      brachymetatarsia is presented with an introduction of a unique autogenous choice.
      This involves the harvesting of bone from the second and third digits of the
      ipsilateral foot and transplanting it to the hypoplastic fourth metatarsal. A
      case study is discussed with its indications, techniques, and results. Provided
      in the case study are photographs of preoperative and postoperative x-rays with a
      follow-up of 14 months.

PMID- 8252009
TI  - Complications secondary to the use of standard bone wax in seven patients.
AB  - Ordinary bone wax, manufactured from beeswax, was used to stop bleeding from
      cancellous bone in elective surgery among seven women. Five of them had a
      resection of a calcaneal exostosis and bursa at the insertion of the calcaneous
      tendon, one underwent a resection of a medial exostosis of the first metatarsal
      head, and one had an acromial resection. Postoperatively, all patients had
      disabling local pain and tenderness. Three of them developed firm visible
      swellings where bone wax had been used, which was easily palpable under the
      intact skin. At reoperation, 4 to 52 months later, masses of brown, soft
      granulation tissue were excised in all patients. Five of seven were relieved from
      pain. Microscopically, a bone wax granuloma with marked foreign body reaction was
      seen in all patients.

PMID- 8252010
TI  - Syndactylism with keloid scar formation.
AB  - A 19-year-old Arab woman who was previously operated on to desyndactylize her
      right second and third digits is presented in this case report. The patient's
      toes resyndactylized postoperatively and a keloid scar developed on the dorsum of
      her incision site. Syndactylism of digits is often discussed when involving the
      hand. However, it is much less frequently presented when it involves the foot,
      because surgical intervention is seldom necessary unless foot function is
      affected. Keloid scars are commonly encountered and pose a challenge to the
      podiatric physician because of their recalcitrant and recurrent tendency. This
      paper, detailing complete podiatric surgical treatment, is presented with a
      review of literature aiming to consolidate the presently known facts about
      syndactylism and keloids, and their treatment in the foot.

PMID- 8252011
TI  - The values of talonavicular angles in patients with pes planus.
AB  - Talonavicular angles of 42 patients with flatfeet were measured using their
      weightbearing and nonweight-bearing anteroposterior and lateral radiographs.
      These patients were divided into two subgroups depending on the presence of pain.
      The normal feet of 22 people were included in this study to establish the control
      group. It was observed that, at the weightbearing position, the talonavicular
      angle increases. The talonavicular angle decreases in pes planus on the lateral
      radiographs. In patients presenting painful flatfeet, the talonavicular angle
      significantly reduces in the nonweightbearing anteroposterior x ray. The reason
      for pain may be enlargement of the medial border of the navicular bone or the
      presence of an accessory navicular bone. Relief of pain was observed in four
      patients following removal of the accessory navicular bone.

PMID- 8252012
TI  - First metatarsophalangeal joint arthrodesis utilizing a mini-Hoffman External
      Fixator.
AB  - Arthrodesis was initially indicated for severe hallux valgus and hallux rigidus.
      Today, it is primarily a salvage procedure, which provides a painless first
      metatarsophalangeal joint. This manuscript reviews the various procedures for
      arthrodesis of the first metatarsophalangeal joint. A case report is presented
      utilizing arthrodesis as a salvage procedure for a painful first
      metatarsophalangeal joint, after previously failed procedures.

PMID- 8252013
TI  - Foot alterations in the hemodialyzed patient.
AB  - On the basis of their experience, the authors refer to complications observable
      at the foot level in chronic uremic patients in long-term hemodialytic treatment.
      These complications, termed renal osteodystrophy, are attributed to alterations
      in the phosphocalcium metabolism and to hyperparathyroidism. From an
      anatomopathologic viewpoint, they are characterized by alteration in bone tissue
      (osteomalacia and/or fibrous osteitis) and by soft tissue alterations.
      Alterations in the foot are the same as those observed in other osteoarticular
      regions. They consist of bone subperiosteal reabsorption of the phalanges,
      vascular calcifications, articular and para-articular calcifications, spontaneous
      disinsertion of the Achilles tendon and peripheral canalicular neuropathies
      specifically represented by the tarsal tunnel syndrome. Another complication of
      this pathology is represented by "Calciphylaxis," characterized by calcifications
      of the middle tunica of arteries and small arteries, by ulcerations and tissue
      necrosis at the foot level.

PMID- 8252014
TI  - Avascular necrosis of the first metatarsal head following Austin osteotomy: a
      follow-up study.
AB  - A prospective study is described of 12 consecutive patients with hallux abducto
      valgus deformity in whom an Austin osteotomy without lateral release was
      performed. All patients had similar postoperative care and magnetic resonance
      images (MRI) studies of their first metatarsals. The MRI was performed in T1- and
      T2-weighted images with algorithms programmed to image changes in the bone
      consistent with avascular necrosis of the first metatarsal head. One of the 12
      patients following Austin osteotomy without lateral release had changes on MRI
      consistent with avascular necrosis of the first metatarsal head. These results
      were then compared with the prior study of 20 patients that had the Austin
      osteotomy with lateral release using the Fisher's exact test for small
      populations, and a value of 0.023 was found (0.05 > 95% confidence level). The
      Austin osteotomy with lateral release significantly increases the risk of
      developing avascular necrosis of the first metatarsal head and should only be
      performed in instances where the soft tissue contracture is largely contributing
      to the hallux abducto valgus deformity.

PMID- 8252015
TI  - The use of skin stapling in podiatric surgery: a review and update.
AB  - The ideal method for wound closure remains an enigma. This paper presents a
      review and the authors' experience of the use of skin staples in podiatric
      surgery. Little has been written on this topic in the podiatric literature. Skin
      staples have been shown to provide desirable cosmetic results, a decreased
      incidence of infection, and a decrease in overall cost as compared with suture.

PMID- 8252016
TI  - Leiomyosarcoma: a rare pedal finding.

PMID- 8252017
TI  - Are obstructing ureteral stones more difficult to treat with extracorporeal
      electromagnetic shock wave lithotripsy?
AB  - In situ extracorporeal shock wave lithotripsy (ESL) has increasingly become
      accepted for the treatment of ureteral stones. However, treatment success is
      negatively affected by stone impaction or associated urinary obstruction. In
      order to assess the impact of obstruction on the outcome of in situ ESL, we
      reviewed the results in 503 patients treated in this way. The presence and
      severity of urinary obstruction was defined prior to ESL, being classified as no
      or mild obstruction (Group I) and moderate or severe obstruction (Group II). The
      stone-free rate in the nonobstructed group was 90%, whereas it was 85% in the
      obstructed group (P > 0.005). While all of our patients were treated on an
      outpatient basis, two patients in Group I and four patients in Group II required
      hospitalization with the diagnosis of pyelonephritis. All six patients were
      treated successfully with appropriate measures. No other serious complication
      occurred that required hospitalization. We conclude that urinary obstruction does
      not affect stone disintegration or passage and suggest that in situ ESL should be
      the treatment of choice in ureteral stones.

PMID- 8252018
TI  - Extracorporeal shock wave lithotripsy monotherapy of staghorn calculi with
      Dornier MFL 5000.
AB  - A retrospective study was conducted of the efficacy of extracorporeal shock wave
      lithotripsy (SWL) monotherapy for the management of 31 patients with staghorn
      calculi (mean size 5.2 cm2). Five patients were lost to follow-up, 10 were stone
      free in the end, and 11 had effective disintegration with small residual
      fragments. The remaining five patients required open surgery because of
      insufficient stone fragmentation. According to our data, SWL monotherapy is not
      sufficient for achieving stone-free status in patients with staghorn calculi, but
      it relieves obstruction and decreases the stone bulk in the majority of them.

PMID- 8252019
TI  - Anesthesia-free extracorporeal shock wave lithotripsy of distal ureteral stones
      without a ureteral catheter.
AB  - The therapeutic results of extracorporeal shock wave lithotripsy (SWL) for distal
      ureteral stones were compared between 70 patients treated without a ureteral
      catheter (Group 0) and 142 patients treated during a period when attempts always
      were made to pass the stone with a catheter before the treatment (Group UC). All
      SWL procedures were carried out with an unmodified Dornier HM3 lithotripter and
      with only analgosedation with pethidine (meperidine) and diazepam. One shock wave
      session was sufficient in 76% of the patients in Group 0 and in 77% of those in
      Group UC. There were no differences between the groups in terms of need for
      retreatment and the mean numbers of sessions were 1.37 +/- 0.79 (SD) in Group 0
      and 1.28 +/- 0.61 in Group UC (P > 0.05). The stone-free rate after 4 weeks was
      96% and 97%, respectively. This result was achieved without ureteral
      manipulations after SWL in 89% of the patients in Group 0 and in 95% of the
      patients in Group UC (P > 0.05). The number of shock waves and the energy index
      were lower in Group 0 than in Group UC (P < 0.001). Patients with distal ureteral
      stones apparently can be treated with SWL without a ureteral catheter with
      approximately the same success rate as with a catheter. The use of a catheter
      might, however, be of value for easy localization of scarcely radiopaque stones
      and possibly in some cases of seriously impacted stones, as well as for treatment
      of children, who regularly require general anesthesia.

PMID- 8252020
TI  - Cost-efficacy comparison of extracorporeal shock wave lithotripsy and endoscopic
      laser lithotripsy in distal ureteral stones.
AB  - Distal ureteral stones are usually treated today by extracorporeal shock wave
      lithotripsy or extraction by retrograde ureteroscopy with or without previous
      fragmentation. We performed a cost-efficacy study of three methods to treat them:
      extracorporeal lithotripsy using either a spark gap lithotripter, the unmodified
      Dornier HM3 (SWL), or the piezoelectric Wolf Piezolith 2300 (EPL) and endoscopic
      lasertripsy (LISL) using an alexandrite pulsed laser, the HMT Alexantriptor. The
      records of 520 patients with distal ureteral stones treated by extracorporeal
      lithotripsy were reviewed to establish the mean cost of the procedure. Concerning
      LISL, the first 30 stone patients treated in our institution were evaluated. Four
      measures were examined: (1) number of sessions; (2) success rate; (3) auxiliary
      maneuvers; and (4) complications. The economics evaluation considered the direct
      costs related to personnel, consumables, depreciation, and maintenance. The EPL
      procedure was the cheapest: $873 US, and SWL the most expensive: $3,572 US. The
      best cost-efficacy rate was seen with LISL because of its 93% success rate and
      its cost of $1,390 US.

PMID- 8252021
TI  - Percutaneous nephrolithotomy for large and staghorn calculi.
AB  - The treatment of choice for a stone load of up to 3 cm is indubitably
      extracorporeal shock wave lithotripsy (SWL). However, for larger stones, and
      particularly staghorn calculi, the choice is not that clearcut. Our experience
      with percutaneous nephrolithotomy (PCNL) for a stone load larger than 3 cm in 878
      renal units over 9 years has left us convinced that a well-planned and determined
      effort at percutaneous clearance is the best option for these difficult cases.
      Our overall complete clearance rate in this group is 93% and ranges from 98.5%
      for solitary calculi to 71% for complete staghorn calculi. These results are
      comparable to those reported by other workers with percutaneous monotherapy and
      are superior to those achieved by SWL monotherapy. The complication rate was
      acceptably low at 4%. We conclude that the expeditiousness and the better stone
      free rates of PCNL justify the slightly higher morbidity that it entails when
      compared with SWL monotherapy. We also prefer to aim for total clearance
      percutaneously, leaving for SWL only those stones that defy our best efforts.

PMID- 8252022
TI  - Long-term results of endourologic treatment of urinary calculi: investigation of
      risk factors for recurrence or regrowth.
AB  - To evaluate the risk factors related to the long-term outcome of endourologic
      treatment of urinary calculi, we examined rates of recurrence and regrowth in 167
      renal units. The following risk factors were examined: age; previous stone;
      location, number, size, and composition of stone; and procedures. In our study
      sample, the overall recurrence and regrowth rates were 17% and 10%, respectively.
      The earliest recurrence and regrowth appeared at 3 months after treatment, and
      71% occurred within 2 years. In 22% of renal units that were estimated to be
      stone-free, stones appeared later, and 45% of inadequately fragmented stones
      enlarged. Stones located in a renal calix and pelvis, multiple stones, large
      stones (more than 20 mm), stones composed of calcium oxalate or calcium phosphate
      or both, and struvite stones were likely to be risk factors, but there were no
      significant differences statistically. Although the possibility of several risk
      factors was suggested in our study, thorough fragmentation of stones and complete
      removal of fragments, combined with extracorporeal shock wave lithotripsy or
      chemolysis if needed, is ultimately responsible for successful treatment of
      urinary calculi.

PMID- 8252023
TI  - Laparoscopically controlled and assisted percutaneous transperitoneal
      nephrolithotomy in a pelvic dystopic kidney.
AB  - Two renal pelvic stones were removed percutaneously from a pelvic dystopic kidney
      using a transabdominal, transperitoneal approach. The puncture was made antegrade
      and controlled partly fluoroscopically and partly laparoscopically. Where the
      kidney was covered by bowels, these were displaced with forceps inserted through
      another laparoscopic trocar. The dilation and stone removal were performed
      traditionally. As the kidney was just behind the uterus, the authors considered
      extracorporeal lithotripsy contraindicated in this case, so the only minimally
      invasive resolution was percutaneous nephrolithotomy, which could be performed
      only with the aid of laparoscopy.

PMID- 8252024
TI  - Prone split leg and flank roll positioning: simultaneous antegrade and retrograde
      access to the upper urinary tract.
AB  - The simultaneous endoscopic approach to upper urinary tract pathology in both an
      antegrade and retrograde fashion can be cumbersome. The prone split leg and flank
      roll positions allow such simultaneous access. Of 111 patients in whom the prone
      split leg position was employed, 41% were treated with simultaneous antegrade and
      retrograde endoscopy in a two-team approach. Treating large staghorn calculi in
      this manner, one team debulked the stone burden accessible through the flank
      nephroscopically, while another team approached the remainder of the stone burden
      using the pulsed-dye laser ureteroscopically in a retrograde manner. The flank
      roll position was employed in 15 patients who presented with percutaneous
      nephrostomies and were deemed treatable preoperatively in a retrograde manner.
      They were positioned in this manner to allow intraoperative access to the
      percutaneous nephrostomy tract. Nine of these patients required antegrade
      treatment. The application of these two positions and the concept of the two-team
      approach added to the efficiency of treating not only staghorn calculi, but other
      upper tract pathology. Simultaneous procedures require at least two skilled
      endoscopists as well as dual light sources, various lithotrites, and several
      rigid and flexible endoscopes.

PMID- 8252025
TI  - Ureteroscopic cytologic diagnosis of upper tract lesions.
AB  - The definitive diagnosis of upper urinary tract lesions often relies on providing
      adequate tissue samples for cytopathologic review. Uretreopyeloscopy allows
      direct examination of these lesions and enables tissue sampling under visual
      control. A retrospective analysis of 11 patients with 13 abnormal upper tracts
      was performed, comparing sampling techniques performed under endoscopic vision
      (brush biopsy, fine-needle aspiration [FNA], and forceps biopsy) with standard
      retrograde catheter lavage. Forceps biopsy was the most accurate of the direct
      vision sampling methods (100%), although it provided adequate tissue only 56% of
      the time. Direct vision brush biopsy and FNA were better than forceps biopsy at
      providing adequate tissue but were less accurate, at 83% and 89%, respectively.
      Surprisingly, retrograde catheter lavage was superior to direct vision sampling
      methods. These results may be attributable to patient selection bias in that five
      of seven upper tracts found to have malignancy had multifocal disease. One
      patient developed a distal ureteral stricture from instrumentation that was
      managed successfully with an endoureterotomy.

PMID- 8252026
TI  - Laparoscopic pyelocaliceal diverticula ablation.
AB  - Pyelocaliceal diverticula are cystic urine collections within the renal
      parenchyma communicating with the collecting system. They occur in 0.2% to 0.5%
      of the population and often contain calculi. Flank pain is the most common
      complaint, and most lesions are diagnosed by intravenous urography. In the past,
      treatment has required open renal surgery, with potential loss of renal function,
      or prolonged percutaneous procedures. We propose surgical treatment of caliceal
      diverticula by laparoscopic unroofing and fulguration. The benefits include renal
      preservation as well as decreased morbidity and an earlier return to work for the
      patient.

PMID- 8252027
TI  - Laparoscopic needle colposuspension for genuine stress incontinence.
AB  - Laparoscopic needle colposuspension offers a minimally invasive endosurgical
      treatment of genuine stress incontinence. With the patient in the low lithotomy
      position, three lower abdominal ports are inserted. Bilateral incisions are made
      in the peritoneum, and the retropubic space is dissected, leaving the urachus
      intact. A suprapubic incision is made down to rectus fascia only and a Stamey
      needle inserted into the retropubic space and passed into the vagina under
      vision. Using No. 1 Ethibond, a double bite of the vaginal wall is taken and the
      suture pulled into the suprapubic incision. The suture is tied over a silicone
      button with no slack and no tension. Seven women have been treated by this
      method, with all having control of their stress incontinence in the short term.
      The mean operative time was 112 minutes. The catheter was removed on the first
      postoperative day in six women and on the second day in one woman, with no
      voiding difficulties. The mean time to discharge was 3.3 days for all except one
      woman, who had a perforation of the bladder and remained for 12 days. The
      advantages of the laparoscopic approach are that it allows dissection of the
      retropubic space, direct examination of the bladder, and observation of the
      bladder neck during tying of the sutures, allowing them to be tied with no slack
      and no tension. As a consequence, there is a minimization of the duration of
      catheterization, voiding difficulties, hospital stay, and postoperative
      discomfort, with avoidance of scarring of the vaginal wall and urethra.

PMID- 8252028
TI  - Percutaneous extra-anatomic nephrovesical diversion: preliminary report.
AB  - We propose a new approach to total ureteric replacement based on the use of a new
      spiraled composite tube. This tube is inserted percutaneously into the renal
      pelvis, then tracked subcutaneously and introduced into the bladder via a short
      incision. The tube is maintained in place by anchoring its spirals along the
      subcutaneous tract, and only the two silicone extremities are in continuous
      contact with the urine. We have used this technique for total replacement of the
      ureter in one renal transplant patient with a follow-up of 8 months and no
      complication. A longer follow-up is obviously necessary, but this new, minimally
      invasive approach, using a newly designed tube, would appear to give a new lease
      of life to an old, abandoned principle.

PMID- 8252029
TI  - Use of multiple Wallstents in treatment of bladder outlet obstruction.
AB  - Of 23 patients being treated with the Urolume Wallstent for bladder outlet
      obstruction, 4--3 with anterior urethral strictures and 1 with benign prostatic
      hyperplasia--required two to four stents. When placing multiple stents, there
      should be enough overlap to prevent the opening of a gap as the stents expand and
      shorten over the ensuing weeks. Use of more than 1 stent is indicated when the
      stricture or the prostatic urethra is longer than 3 cm or when stricture recurs
      beyond the end of a previously placed stent.

PMID- 8252030
TI  - Treatment of persistent lymphatic drainage after laparoscopic pelvic lymph node
      dissection and radical retropubic prostatectomy.
AB  - A patient with a lymphocele after laparoscopic pelvic lymphadenectomy and radical
      retropubic prostatectomy was treated successfully with a single instillation of
      diatrizoate meglumine through a Jackson-Pratt drain. The authors review the
      origin of lymphoceles and various methods for treating them.

PMID- 8252031
TI  - Breast cancer on the brink.

PMID- 8252032
TI  - All in the (cancer) family.

PMID- 8252033
TI  - Homozygosity mapping: familiarity breeds debility.

PMID- 8252034
TI  - Male breast cancer and the androgen receptor gene.

PMID- 8252035
TI  - The rapid detection of unknown mutations in nucleic acids.
AB  - The task of identifying mutations in nucleic acid sequences is a vital component
      of research in mammalian genetics. With the advent of the polymerase chain
      reaction, several useful mutation detection techniques have evolved in recent
      years. The different methods have complementing strengths and a suitable
      procedure for virtually any experimental situation is now available.

PMID- 8252036
TI  - Cloning of the human aspartoacylase cDNA and a common missense mutation in
      Canavan disease.
AB  - Canavan disease, an autosomal recessive leukodystrophy, is caused by deficiency
      of aspartoacylase and accumulation of N-acetylaspartic acid in brain. We have
      cloned the human aspartoacylase (ASP) cDNA spanning 1,435 basepairs, and show
      that the isolated cDNA expresses aspartoacylase activity in bacteria.
      Furthermore, an A to C base change, at nucleotide 854, has been found in 85% of
      the 34 Canavan alleles tested so far. This base change results in a missense
      Glu285Ala mutation that is predicted to be part of the catalytic domain of
      aspartoacylase. The data suggest that the catalytic centre of aspartoacylase
      involves a triad of Ser, His and Glu residues. Our findings have implications for
      diagnosis and screening of Canavan disease.

PMID- 8252037
TI  - Screening patients for heterozygous p53 mutations using a functional assay in
      yeast.
AB  - Inherited mutations of the p53 gene significantly increase the risk of developing
      diverse malignancies, and germline p53 mutations can be detected by assaying the
      transcriptional activity of the p53 protein in mammalian cells. Here we describe
      a method starting with lymphocytes that allows detection of germline p53
      mutations by 'functional' analysis of p53 protein expressed in Saccharomyces
      cerevisiae. The p53 PCR products are directly cloned into yeast expression
      vectors in vivo and subsequently tested for transcriptional activity in a simple
      growth assay. This technique, functional analysis of separated alleles in yeast
      (FASAY), requires only a few steps, can be automated readily and should permit
      screening for germline or somatic heterozygous mutations in any gene whose
      function can be monitored in yeast.

PMID- 8252038
TI  - Long-term correction of mouse dystrophic degeneration by adenovirus-mediated
      transfer of a minidystrophin gene.
AB  - Duchene muscular dystrophy (DMD) is a fatal progressive X-linked muscle disorder,
      caused by mutations in the dystrophin gene. We have investigated adenovirus
      mediated transfer of a dystrophin minigene in a mutant mouse lacking dystrophin,
      the mdx mouse. We report here that six months after a single intramuscular
      injection of a recombinant adenovirus containing a human dystrophin minigene, a
      large number of dystrophin-positive fibres are still detected in the injected
      muscles. Moreover, although the minigene encodes a truncated protein, its
      expression is able to protect the fibres efficiently against the degeneration
      process that affects the dystrophin-deficient mdx myofibres.

PMID- 8252039
TI  - Disruption of insulin-like growth factor 2 imprinting in Beckwith-Wiedemann
      syndrome.
AB  - To study insulin-like growth factor 2 (IGF2) imprinting in BWS (Beckwith
      Wiedemann syndrome, an overgrowth syndrome associated with Wilms and other
      embryonal tumours), we examined allele-specific expression using an Apal
      polymorphism in the 3' untranslated region of IGF2. Four of six BWS fibroblast
      strains demonstrated biallelic expression, as did the tongue tissue from one of
      these patients. Paternal heterodisomy was excluded for all BWS patients with
      biallelic expression, suggesting strongly that the BWS phenotype in some patients
      involves disruption of IGF2 imprinting. Constitutional loss of IGF2 imprinting in
      a subgroup of our BWS patients, and recent reports of loss of imprinting in
      sporadic Wilms tumour, further strengthens the view that IGF2 overexpression
      plays an important role in somatic overgrowth and the development of embryonal
      tumours.

PMID- 8252040
TI  - A novel metalloprotease/disintegrin-like gene at 17q21.3 is somatically
      rearranged in two primary breast cancers.
AB  - From chromosomal region 17q21.3, where a tumour suppressor gene(s) for breast and
      ovarian cancers is thought to be present, we have isolated a novel gene from a
      cosmid clone that revealed somatic rearrangements in two breast cancers. The gene
      (MDC) encodes a 524-amino acid metalloprotease-like, disintegrin-like and
      cysteine-rich protein with sequence similarity to members of the snake-venom
      metalloprotease/disintegrin family and guinea-pig sperm-surface protein PH-30.
      These proteins have been implicated in cell-cell or cell-extracellular matrix
      interactions. Rearrangements in both tumours involve multiple exons and disrupt
      the coding region of the new MDC.

PMID- 8252041
TI  - Autosomal dominant familial spastic paraplegia is genetically heterogeneous and
      one locus maps to chromosome 14q.
AB  - Autosomal dominant familial spastic paraplegia (FSP) is a degenerative disorder
      of unknown aetiology characterized by a progressive spasticity of the legs. Three
      families with autosomal dominant FSP of early onset were analysed in linkage
      studies using highly polymorphic microsatellite markers. Close linkage to a group
      of markers on chromosome 14q (maximum multipoint lodscore z = 10) was observed in
      one family. This chromosome 14q candidate region was entirely excluded in the two
      other families, providing evidence of genetic heterogeneity within a homogeneous
      clinical form of FSP.

PMID- 8252042
TI  - De novo expansion of a (CAG)n repeat in sporadic Huntington's disease.
AB  - Huntington's disease (HD) chromosomes contain an expanded unstable (CAG)n repeat
      in chromosome 4p16.3. We have examined nine families with potential de novo
      expression of the disease. With one exception, all of the affected individuals
      had 42 or more repeat units, well above the normal range. In four families,
      elderly unaffected relatives inherited the same chromosome as that containing the
      expanded repeat in the proband, but had repeat lengths of 34-38 units, spanning
      the gap between the normal and HD distributions. Thus, mutation to HD is usually
      associated with an expansion from an already large repeat.

PMID- 8252043
TI  - Molecular analysis of new mutations for Huntington's disease: intermediate
      alleles and sex of origin effects.
AB  - Huntington's disease (HD) is associated with expansion of a CAG repeat in a novel
      gene. We have assessed 21 sporadic cases of HD to investigate sequential events
      underlying HD. We show the existence of an intermediate allele (IA) in parental
      alleles of 30-38 CAG repeats in the HD gene which is greater than usually seen in
      the general population but below the range seen in patients with HD. These IAs
      are meiotically unstable and in the sporadic cases, expand to the full mutation
      associated with the phenotype of HD. This expansion has been shown to occur only
      during transmission through the male germline and is associated with advanced
      paternal age. These findings suggest that new mutations for HD are more frequent
      than prior estimates and indicate a previously unrecognized risk of inheriting HD
      to siblings of sporadic cases of HD and their children.

PMID- 8252044
TI  - A mutation in the Norrie disease gene (NDP) associated with X-linked familial
      exudative vitreoretinopathy.
AB  - Familial exudative vitreoretinopathy (FEVR) is a hereditary disorder
      characterized by an abnormality of the peripheral retina. Both autosomal dominant
      (adFEVR) and X-linked (XLFEVR) forms have been described, but the biochemical
      defect(s) underlying the symptoms are unknown. Molecular analysis of the Norrie
      gene locus (NDP) in a four generation FEVR family (shown previously to exhibit
      linkage to the X-chromosome markers DXS228 and MAOA (Xp11.4-p11.3)) reveals a
      missense mutation in the highly conserved region of the NDP gene, which caused a
      neutral amino acid substitution (Leu124Phe), was detected in all of the affected
      males, but not in the unaffected family members, nor in normal controls. The
      observations suggest that phenotypes of both XLFEVR and Norrie disease can result
      from mutations in the same gene.

PMID- 8252045
TI  - Reduced transcriptional regulatory competence of the androgen receptor in X
      linked spinal and bulbar muscular atrophy.
AB  - Expansion of the long (CAG; glutamine)n repeat in the first exon of the X-linked
      human androgen receptor gene (hAR) causes spinal and bulbar muscular atrophy,
      frequently in association with mild androgen insensitivity. The relevant normal
      motor neurons are preferentially stimulated by androgen, however no motor neuron
      disorder occurs with any other known AR mutation, including those that cause
      complete androgen insensitivity. We have found that a polyglutamine (Gln)
      expanded AR transactivates an androgen-responsive reporter gene subnormally.
      Other groups have reported that a poly Gln-deleted AR transactivates normally. A
      parsimonious interpretation of all these facts is that poly Gln expansion causes
      the AR to lose a function that is necessary for full androgen sensitivity and to
      gain a function that is selectively motor neuronotoxic.

PMID- 8252046
TI  - Evidence for a recessive PMP22 point mutation in Charcot-Marie-Tooth disease type
      1A.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant neuropathy
      that can be caused by dominant point mutations in PMP22 which encodes a
      peripheral nerve myelin protein. Usually, CMT1A is caused by the duplication of a
      1.5-megabase (Mb) region on chromosome 17p11.2-p12 containing PMP22. Deletion of
      a similar 1.5-Mb region is associated with hereditary neuropathy with liability
      to pressure palsies (HNPP), a clinically distinct neuropathy. We have identified
      a severely affected CMT1 patient who is a compound heterozygote for a recessive
      PMP22 point mutation, and a 1.5 Mb deletion in 17p11.2-p12. A son heterozygous
      for the PMP22 point mutation had no signs of neuropathy, while two others
      heterozygous for the deletion had HNPP, suggesting that point mutations in PMP22
      can result in dominant and recessive alleles contributing to CMT1A.

PMID- 8252047
TI  - Localization of Friedreich ataxia phenotype with selective vitamin E deficiency
      to chromosome 8q by homozygosity mapping.
AB  - Friedreich ataxia and ataxia with selective vitamin E deficiency (AVED) share
      very similar clinical phenotypes. We have mapped the AVED locus to proximal 8q
      with only three large consanguinous Tunisian families, representing to our
      knowledge the first use of homozygosity mapping for primary linkage analysis.
      Subsequently, three additional families showed linkage with the same markers. A
      maximum lod score of 17.9 was obtained at theta = 0 for the haplotype D8S260
      D8S510, consisting of the two closest markers. With only 6 families, the AVED
      locus is therefore mapped precisely as illustrated by the lod-1 confidence
      interval of 2.4 cM on either side of D8S260-D8S510. Isolation of a yeast
      artificial chromosome contig > 800 kilobases (kb) showed that D8S260 and D8S510
      are less than 400 kb apart.

PMID- 8252049
TI  - Neurophysiological evaluation in detrusor instability.
AB  - Different and complex neuronal systems are involved in the control of continence.
      Detrusor overactivity has been divided by the International Continence Society
      into two functional subgroups: a) detrusor instability and b) detrusor
      hypereflexia. Only in the latter group has neurological damage been shown, but
      pathophysiological mechanisms are still unknown. In order to complete a full
      investigation of sensory and motor pathways 12 female patients affected by
      idiopathic detrusor instability (mean age 60.2 years; range 49-73) and 13 age
      matched healthy women were studied. All patients were submitted to a subtracted
      cistometrogram (CMG), anal sphincter electromyography (EMG) with a bipolar
      coaxial needle, sacral reflex analysis after stimulation of the dorsal nerve of
      the clitoris, tibial and pudendal somatosensory evoked potentials, motor evoked
      potentials after magnetic cortical coil stimulation, and recording from anal
      sphincter and abductor brevis hallucis muscles. All patients had normal
      neurophysiological tests, and no significant differences between patients and
      controls could be seen. Our data confirms the absence of both clinical and
      subclinical damage of central sensory or motor pathways in detrusor instability;
      an alteration of suprasegmental mechanisms cannot be excluded.

PMID- 8252048
TI  - Homozygosity mapping of the gene for alkaptonuria to chromosome 3q2.
AB  - Alkaptonuria, the first human disorder recognized by Garrod as an inborn error of
      metabolism, is a rare recessive condition that darkens urine and causes a
      debilitating arthritis termed ochronosis. We have studied two families with
      consanguineous parents and four affected children in order to map the gene
      responsible for alkaptonuria. Coinheritance of either neonatal severe
      hyperparathyroidism or sucrase-isomaltase deficiency and alkaptonuria provided a
      candidate location for the mutated genes on chromosome 3. Homozygosity mapping
      with polymorphic loci identified a 16 centiMorgan region on chromosome 3q2 that
      contains the alkaptonuria gene. Analysis of two additional nonconsanguineous
      families supports linkage of alkaptonuria to this single locus (combined lod
      score = 4.3, theta = 0).

PMID- 8252050
TI  - New concepts in relation to urge and detrusor activity.
AB  - Investigations of micromotion characteristics of bladder wall strips and pressure
      wave phenomena in total bladders in vitro and in vivo indicate that micromotion
      phenomena occur in the bladder wall. Local contractions can occur without an
      increase in tension or pressure, because other parts are in antiphase. Local
      contractions stretch surrounding tissues, which can stimulate fast stretch
      receptors. Synchronisation of these micromotion phenomena appears to be possible.
      Hence, above threshold levels urge can theoretically occur, even in the absence
      of a pressure increase. This hypothesis could explain the weak relation between
      urge and pressure. The distinction between motor and sensory urge could be
      artifactual based on a misunderstanding of fundamental bladder wall processes.

PMID- 8252051
TI  - Effect of partial urinary outlet obstruction in the rabbit on the incorporation
      of adenine into adenine nucleotides in bladder smooth muscle.
AB  - Bladder outlet obstruction induces marked morphological, functional, and
      metabolic changes within the urinary bladder. Recent studies indicate that there
      is a close correlation between the contractile dysfunction induced by partial
      outlet obstruction and a marked decrease in mitochondrial oxidative activity of
      the hypertrophied bladder tissue. The current study investigates the effect of
      partial outlet obstruction on adenine metabolism within the bladder tissue. After
      transport into the cell, adenine becomes available as a substrate for adenine
      phosphoribosyl transferase (APRT), the enzyme that catalyses the non
      mitochondrial conversion of adenine into AMP. Subsequently, AMP is phosphorylated
      to ADP, the phosphate acceptor in mitochondrial oxidative phosphorylation. The
      results of these studies demonstrate that partial outlet obstruction induces a
      significant increase in 14C-adenine uptake into the urinary bladder smooth muscle
      which in turn provides substrate for APRT and results in an increase in 14C-AMP
      synthesis. In contrast, the rate of incorporation of adenine into ATP+ADP was
      similar for both control and obstructed tissue. The activity of APRT was not
      significantly different in control and obstructed tissue.

PMID- 8252052
TI  - History of the sacral anterior root stimulator, 1969-1982.

PMID- 8252053
TI  - Physiological considerations in the use of sacral anterior root stimulators.

PMID- 8252054
TI  - Concepts of neuromodulation.

PMID- 8252055
TI  - Sacral anterior root stimulation: prerequisites and indications.
AB  - An intact sacral reflex arc, or at least an intact second motor-neuron and a
      detrusor being able to contract, are the two prerequisites for implanting an
      anterior sacral root stimulator. Transrectal electrostimulation or direct needle
      stimulation of the sacral roots may reveal if patients despite absent or only
      weak detrusor contractions on routine investigation are suitable. Patients with a
      complete midthoracic paraplegia are the ideal candidates, but tetraplegics also
      benefit. Patients with incomplete lesions and preserved pain sensations are
      suitable provided that they can undergo posterior sacral root rhizotomy. Non
      traumatic spinal cord lesions follow the same rules, provided that the type of
      lesion does not allow recovery and is not progressive. Myelomeningocele patients
      may be suitable provided that the pathoanatomy of the sacral roots permits the
      operation (may be possible only in thoracolumbar myelomeningocele). Vesico
      uretero-renal reflux is no contraindication; it may even be a strong indication,
      if a low compliance bladder or high detrusor contractions are the main reasons
      for it. In most patients the procedure should or must be combined with posterior
      sacral root rhizotomy in order to normalize a low compliance, to abolish
      spontaneous reflex contractions, and to achieve continence. The benefit of
      following these rules is reflected in our own series of 30 patients. In all of
      them the operation has improved considerably the quality of life and no patient
      so far has regretted the operation.

PMID- 8252056
TI  - The "Barcelona" technique.

PMID- 8252057
TI  - Worldwide experience with the Finetech-Brindley sacral anterior root stimulator.

PMID- 8252058
TI  - Sacral root stimulation.

PMID- 8252059
TI  - Why does continence fail after sacral anterior root stimulator?

PMID- 8252060
TI  - Evolution of bladder contraction in course of time after implantation of a sacral
      anterior root stimulator.
AB  - We reviewed bladder contraction evolution after sacral anterior root stimulator
      implantation in thirty patients operated on from 1984 to 1991. Two patients
      underwent a complete denervation with a reinnervation within a maximal time of
      seventeen months. One patient underwent a lesion, like a neuropraxia with a
      complete recovery at four months. Five patients have undergone a partial
      denervation with a recovery of miction by neurostimulation within the time of
      eighteen months. In three patients, bladder contraction disappeared for various
      reasons.

PMID- 8252061
TI  - Adjuvant drug therapy: a review of 30 cases of sacral anterior root stimulator.
AB  - Implantation of a sacral anterior root stimulator in spinal cord injured patients
      must achieve two main goals to maintain a vesicosphincteral balance: complete
      bladder voiding and correct continence. During the postoperative period,
      difficulties may arise or persist with either an incontinence due to an
      insufficient deafferentation with bladder hyperreflexia or an incomplete voiding
      because of an insufficient contraction of detrusor and/or too high urethral
      resistances (vesicosphincteral dyssynergia). A third of our patients required
      specific therapies after implantation to promote interstimulation continence and
      complete bladder voiding. Regarding continence, adjuvant therapies are effective
      for bladder hyperreflexia in connection with a too-partial deafferentation. On
      the other hand, these therapies have little effect on low bladder compliance. In
      regard to bladder voiding, nonsurgical treatments are equally effective. These
      treatments (parasphincteral infiltrations, alpha-blockers) must not be permanent,
      but allow a reharmonizing between expulsive strengths and urethral resistances.
      Eighty percent of our patients who required adjuvant therapies have been improved
      significantly. This confirms the efficiency of adjuvant therapy and speaks for
      patience.

PMID- 8252062
TI  - Future directions.

PMID- 8252063
TI  - Interconversion of the salicylic acid signal and its glucoside in tobacco.
AB  - Salicylic acid (SA) has been proposed to play a role in the induction of
      pathogenesis-related (PR) proteins and systemic acquired resistance (SAR) in
      tobacco. Since SA is rapidly converted to salicylic acid beta-glucoside (SAG) in
      tobacco, we have attempted to assess the role of SAG in pathogenesis by
      application of chemically synthesized SAG to tobacco leaves. SAG was as active as
      SA in induction of PR-1 gene expression. This induction was preceded by a
      transient release of SA, which occurred in the extracellular spaces. The
      existence of a mechanism that releases SA from SAG suggests a possible role for
      SAG in SAR.

PMID- 8252065
TI  - Constitutive, light-responsive and circadian clock-responsive factors compete for
      the different l box elements in plant light-regulated promoters.
AB  - The l box is a conserved regulatory motif which is found upstream of plant genes
      (rbcS, cab and nia) whose transcription is regulated by light and the circadian
      clock. Gel retardation and UV cross-linking assays were used to resolve two
      different groups of I box binding factors (IBFs) in tomato nuclear extracts.
      Active components of the first group (IBF-1) recognize the l box of the light
      responsive rbcS promoter; one factor within this group, IBF-1a, also recognizes
      the adjacent G box, which has been shown previously to bind a different class of
      plant transcription factors, the G box binding factors (GBFs). To the limit of
      experimental resolution, IBF-1a and GBF compete for the same nucleotides on the G
      box. Nevertheless, these two activities are biochemically and immunologically
      distinct. The relative abundance of IBF-1a shows a vast decrease in dark-adapted
      plants. Factors in the second group (IBF-2), recognize the l box of the nia
      promoter, which is regulated both by light and the circadian clock; one factor
      within this group, IBF-2a, also binds the l box of a second promoter showing
      similar regulation, the cab promoter. The IBF-2a binding sites on the cab and nia
      promoters show extensive homology to a circadian clock-responsive promoter
      element from wheat. The abundance of IBF-2a is diurnally regulated and shows a
      dramatic induction around the onset of the light period. Transfer of the plants
      in continuous darkness demonstrates that this induction is under the control of a
      circadian clock.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252064
TI  - A sink-specific H+/monosaccharide co-transporter from Nicotiana tabacum: cloning
      and heterologous expression in baker's yeast.
AB  - A cDNA clone for a monosaccharide transporter (MST1) was isolated from tobacco,
      which is most strongly expressed in the various sink tissues of mature tobacco
      plants: roots, flowers, and young leaves. An open reading frame of 1569 bp codes
      for a protein with 523 amino acids and a calculated molecular weight of 57,717
      Da. The protein is homologous to a group of other plant monosaccharide transport
      proteins from Arabidopsis thaliana and Chlorella kessleri, to human glucose
      transporters and to Saccharomyces cerevisiae and several bacterial sugar
      transport proteins. As with these other transporters, the MST1 protein is
      extremely lipophilic and has 12-putative membrane-spanning domains. Heterologous
      expression of the MST1 cDNA clone in Saccharomyces cerevisiae allowed its
      characterization as a putative H+/monosaccharide co-transporter, catalyzing the
      uptake of hexoses (e.g. D-glucose and D-galactose) or pentoses (e.g. D-xylose)
      and the energy dependent and uncoupler sensitive accumulation of non
      metabolizable substrates (e.g. D-xylose or 3-O-methyl-glucose). Polyclonal
      antibodies were raised against a fusion protein of beta-galactosidase and the
      last 27 amino acids of the C-terminus of the MST1 protein. In SDS extracts of
      transformed yeast cells these antibodies recognize a polypeptide with an apparent
      molecular weight of 42 kDa, which is absent in extracts from untransformed
      control cells.

PMID- 8252066
TI  - RNA editing in maize chloroplasts is a processing step independent of splicing
      and cleavage to monocistronic mRNAs.
AB  - The psbB operon contained in the plastomes of higher plants consists of the genes
      psbB, psbH, petB and petD. The primary transcript of this operon is subject to a
      series of processing steps which include cleavages resulting in four
      monocistronic mRNAs and splicing of the petB and petD transcripts. A search for
      editing sites within the two latter transcripts from maize led us to the
      detection of one editing site within the petB coding region which is conserved at
      the DNA level in other graminean species and in tobacco. This shows that editing
      must be considered as an additional processing step of the psbB operon encoded
      primary transcript. As is evident from cDNA sequences derived from the
      dicistronic and/or unspliced petB/D transcripts which are completely edited,
      editing is an early step of mRNA processing which precedes both splicing and
      cleavage to the monocistronic mRNAs and which must, therefore, be independent of
      the latter two steps. This conclusion is confirmed by a similar observation with
      the editing site of the rpl2 transcript which is contained in the polycistronic
      transcript of the rpoA operon, although here only partial editing is observed for
      the unspliced dicistronic rpl23/rpl2 transcript.

PMID- 8252067
TI  - The profilin multigene family of maize: differential expression of three
      isoforms.
AB  - Profilin is a small (12-15 kDa) actin- and phospholipid-binding protein
      previously known only from studies on animals and lower eukaryotes but recently
      identified as a birch pollen allergen. Here we have identified and characterized
      three members of the profilin multigene family from the plant Zea mays. Two cDNAs
      isolated from a maize pollen library (ZmPRO 1 and ZmPRO 3) each have a single,
      large open reading frame encoding a putative polypeptide 131 amino acids long
      with a predicted molecular weight of approximately 14 kDa. A third maize pollen
      cDNA (ZmPRO 2) has two in-frame translation initiation codons. Use of the first
      ATG would result in a polypeptide 137 amino acids long with a molecular weight of
      14.8 kDa. The three maize profilins are highly homologous to each other (> 90%
      nucleotide and amino acid sequence identity) as well as other plant profilins but
      show far less similarity (30-40% amino acid sequence identity) to animal and
      lower eukaryote profilins. Multiple sequence alignments indicate that only nine
      residues are shared by all eukaryotic profilins examined. However, limited
      comparisons reveal domains in the NH2 and COOH termini that have a high degree of
      similarity suggesting functional conservation. The maize gene family size is
      estimated to contain three to six members based on Southern blot experiments with
      gene-specific and coding region probes. Northern blot analysis demonstrates that
      the three maize profilin cDNAs characterized here are utilized in a tissue
      specific manner and are anther or pollen specific.

PMID- 8252068
TI  - Instability of the L6 gene for rust resistance in flax is correlated with the
      presence of a linked Ac element.
AB  - In a programme aimed at tagging rust-resistance genes in flax with the maize
      transposable element Ac, a primary transformant of a line called 'Forge' that is
      homozygous for four rust-resistance genes, L6, M, N and P2, was identified that
      possessed 10 copies of the Ac element, one of which was linked (29 map units) to
      L6. Descendants of this plant, which had from 8 to 15 copies of Ac, were crossed
      to a rust-susceptible line and the progeny screened for rust-susceptible mutants.
      When the Ac linked to L6 was present in the parent, a high frequency of L6
      mutants was observed (29 mutants in 30,575). By contrast, when this Ac was
      absent, no such mutants were observed in 9258 progeny. The background frequency
      of L6 mutants was low (five in 124,088). A detailed analysis was made of the
      first 11 L6 mutants recovered from parents carrying the L6-linked Ac element.
      While none of the mutants possessed a tagged resistance gene, all lacked an RFLP
      marker closely linked to L6, suggesting that deletions were responsible for loss
      of the L6 specificity. In many of the mutants, one or more RFLP markers in the
      vicinity of the linked Ac were also absent. These findings suggest that the
      linked Ac may be inducing chromosome breakage.

PMID- 8252069
TI  - Limited proteolysis of (1,3)-beta-glucan (callose) synthase from Beta vulgaris L:
      topology of protease-sensitive sites and polypeptide identification using Pronase
      E.
AB  - Plasma membrane (PM) vesicles of defined sidedness were obtained from Beta
      vulgaris L. and subjected to limited proteolysis to investigate the topology and
      subunit composition of UDP-glucose: (1,3)-beta-glucan (callose) synthase (CalS).
      Latency experiments demonstrated that protease-sensitive sites on the CalS
      complex are located primarily at the cytoplasmic face of the PM, with little or
      no CalS inactivation occurring as the result of proteolysis at the apoplastic
      face. In the PM-bound form, CalS activity was resistant to inactivation by
      Pronase E, however at least four polypeptides previously implicated as possible
      CalS components (92, 83, 57 and 43 kDa) were extensively hydrolyzed. Polypeptides
      of 31, 29 and 27 kDa resisted Pronase E hydrolysis and were also enriched in CalS
      fractions purified by glycerol gradient centrifugation and product entrapment. In
      contrast to PM-bound CalS, purified CalS was rapidly hydrolyzed by Pronase E,
      indicating that most Pronase E-sensitive sites are deeply embedded within the PM.
      This study provides direct biochemical evidence that hydrophobic integral
      membrane proteins oriented primarily towards the cytoplasmic face of the PM are
      important for callose biosynthesis in Beta. Furthermore, these results form the
      basis of a biochemically derived working model largely consistent with
      morphologically derived models proposed for intramembrane PM-bound, microfibril
      synthesizing complexes in higher plants.

PMID- 8252070
TI  - Molecular characterization of two cDNAs from Sinapis alba L. expressed
      specifically at an early stage of tapetum development.
AB  - Flower formation in the long-day plant Sinapis alba is strictly dependent on an
      inductive light treatment. Differential screening of an apex cDNA library
      prepared 10 days after flower induction against cDNAs from vegetative apices has
      identified two cDNA clones, pSFD10.35 and pSFD10.44, which represent transcripts
      expressed transiently between day 10 and day 20 after induction and which
      disappear before flowers reach maturity. The corresponding full-length cDNAs
      which were isolated, Satap35 and Satap44, display 86% overall sequence identity.
      These cDNAs encode polypeptides with predicted molecular weights of 12.7 and 12.4
      kDa, and isoelectric points of 10.4 and 7.5, respectively. The N-terminal
      portions of the open reading frames have characteristics of signal sequences. In
      situ hybridization reveals that both transcripts are localized exclusively in the
      tapetal cell layer of the anthers. Maximal expression is observed in flower buds
      of approximately 1.5 mm length (tetrad stage). Southern blot analysis
      demonstrates the presence of additional, closely related genes in the Sinapis
      genome, as well as the occurrence of homologous genes in Arabidopsis thaliana,
      Brassica napus and Nicotiana tabacum.

PMID- 8252071
TI  - A plant gene for photolyase: an enzyme catalyzing the repair of UV-light-induced
      DNA damage.
AB  - Photolyases are thought to be critical components of the defense of plants
      against damage to DNA by solar ultraviolet light, but nothing is known about
      their molecular or enzymatic nature. The molecular cloning of a photolyase from
      mustard (Sinapis alba) described here is intended to increase the knowledge about
      this important repair mechanism in plant species at a molecular level. The gene
      encodes a polypeptide of 501 amino acids with a predicted molecular mass of 57
      kDa. There is a strong sequence similarity to bacterial and yeast photolyases,
      with a close relationship to enzymes with a deazaflavin chromophor. The plant
      photolyase is shown to be functional in Escherichia coli which also indicates
      conservation of photolyases during evolution. It is demonstrated that photolyase
      expression in plants is light induced, thus providing good evidence for the
      adaptation of plants to their environment in order to diminish the harmful
      effects of sunlight.

PMID- 8252072
TI  - Isolation and characterization of two related Arabidopsis ocs-element bZIP
      binding proteins.
AB  - Ocs-elements are a group of related, bipartite promoter elements which have been
      exploited by two distinct groups of plant pathogens, Agrobacterium and certain
      viruses to express genes in plants. The genes for two Arabidopsis bZIP (basic
      region-leucine zipper) proteins that bind to ocs-elements have been isolated and
      characterized. The genes, called OBF4 and OBF5, were isolated by screening an
      Arabidopsis genomic library with degenerate oligonucleotides complementary to the
      DNA-binding domains of other plant ocs-element-binding proteins. The OBF4 and
      OBF5 proteins show 53% amino acid identity but low DNA homology. Southern blot
      analysis demonstrated that each of the OBF genes is a member of a small family.
      OBF4 is more similar to the tobacco TGA1a and Arabidopsis TGA1 proteins, while
      OBF5 is more similar to the maize OBF3.1, wheat HBP1b and Arabidopsis aHBP1b
      proteins. The DNA-binding properties of OBF4 and OBF5 were similar although OBF5
      was able to bind simultaneously to both halves of the ocs-element more
      efficiently than OBF4. This difference in binding to the ocs-element between two
      closely related proteins from the same species is potentially significant since
      binding to both halves of the ocs-element is a pre-requisite for in vivo
      transcriptional activity.

PMID- 8252073
TI  - Lipo-oligosaccharides of Rhizobium induce infection-related early nodulin gene
      expression in pea root hairs.
AB  - This paper shows that lipo-oligosaccharides (Nod factors) synthesized by
      Rhizobium bacteria elicit the induction of infection-related early nodulin genes
      (PsENOD5 and PsENOD12) in pea root hairs. R. leguminosarum bv. viciae secretes a
      mixture of Nod factors containing a C18 fatty acid chain with 4 (C18:4) or 1
      double bond (C18:1). Purified Nod factors harbouring either a C18:4 or a C18:1
      acyl moiety induce the expression of the pea early nodulin genes, PsENOD5 and
      PsENOD12, but the kinetics of induction are different. The expression of both
      early nodulin genes is induced in a transient manner by the purified Nod factors
      while a mixture of the Nod factors extends the period during which these genes
      are expressed. In spite of the host-specific nature of the infection process,
      heterologous Nod factors of R. meliloti also induce the expression of PsENOD5 and
      PsENOD12 genes, though with a marked delay compared with the homologous
      compounds.

PMID- 8252074
TI  - [Anatomo-functional changes in the cavernous body in the elderly].
AB  - The main histological alteration that happens to the structure of the corpora
      cavernosa as years go by, is the progressive increase of collagen fibers compared
      to the decrease of both smooth muscle and elastic fibers. This phenomenon is held
      responsible of consequences on the hemodynamic events occurring during the
      erection.

PMID- 8252075
TI  - [Libido-related changes in the elderly].
AB  - Sexual desire can be influenced in elderly men by a number of factors such as
      hormonal abnormalities, socio-cultural conditions, chronic diseases, drugs.
      Testosterone decrease per se is not sufficient to impair sexual function in the
      elderly; social and psychological factors are probably of relevance as it can be
      observed in people living in nursing homes. Diabetes may have a major impact on
      sexual desire. Drugs usually associated with impairment of libido (psychotropic
      drugs, anti-hypertensives) are frequently used by elderly people; alcohol is a
      leading cause of sexual dysfunction, particularly in unfavourable social
      conditions.

PMID- 8252076
TI  - [The "aging" of the male genital system: erection].
AB  - Between 1/2/89 and 31/1/92 we have studied 300 old patients (the average patient
      age was 72 years). We used scores of sexual functionality to study the
      accordances between voluntary and spontaneous erection, the characteristics of
      the erection per age, the frequency of intercourse per age, the sexual
      preferences in males and females. Also the partner's extrangement has been
      valued. These factors together with the socio-economic conditions, in the same
      body causes represent an important obstacle in the sexuality of the old man.

PMID- 8252077
TI  - [Changes in sexuality and fertility in the elderly: ejaculation].
AB  - After the remark of the own results on an epidemiological research about
      andropausal sexual problems, the Authors analyze the alterations of ejaculatory
      mechanism with elderly, focusing frequency and etiopathogenesis. They underline
      the need of prevention of ejaculatory disturbances deriving from chronic disease
      or of iatrogenic origin.

PMID- 8252078
TI  - [Male fertility in the elderly].
AB  - Fertility in the elderly is still a less known argument. We report some news
      about seminal parameters (SP) and testicular hystological parameters (THP) in
      this age. About SP: the volume of the ejaculate, the number and the motility of
      spermatozoa are reduced. The morphology is typical: spermatozoa with coiled tails
      are common. About THP: some testes show a normal hystological architecture;
      others show a reduced volume and some aspects of hypospermatogenesis or
      maturative arrest; others show a very reduced volume, thickness of the tubular
      basal membrane and other signs of cellular regression. These signs are dependent
      upon the vascular insufficiency and the hormonal alterations which may occur in
      the elderly.

PMID- 8252079
TI  - [Andrologic problems and internal pathology in the elderly].
AB  - Population aging is continuously increasing in Italy and in the World.
      Individuals aged 60 years or more are currently 10,500,000 and will be 13,000,000
      in 2015. Life quality in geriatric ages includes the maintenance of sexual power:
      according to recent data (Carrol et al., 1992), 80% of impotence cases are due to
      organic causes. In addition, the use of drugs can cause impotence. Among them
      tiazidic diuretics may cause an increase of sexual disturbances. Other drugs with
      this potential are digitalis, antihypertensive drugs (particularly beta
      blockers), major and minor tranquillizers, antidepressant, H2 receptor
      antagonists, antiparkinsonian cholinergic drugs and estrogens employed in the
      treatment of prostate tumors. Diseases of geriatric age that can alter sexual
      power are diabetes mellitus, ischemic heart disease for the accompanying
      depression and for the use of antidepressants; severe hypertension is complicated
      by impotence in 15% of cases. Among neurological diseases Parkinson's disease and
      multiple sclerosis can be causes of sexual dysfunctions. Patients on hemodialysis
      can be impotent, with recent data (Soloh et al 1992) showing that erythropoietin
      treatment of anemia also improve sexual dysfunctions. Prevention from a geriatric
      standpoint should be base on action on known risk factor as smoking, alcohol
      abuse and dislipidemias and with the activation of a close drug vigilance.

PMID- 8252080
TI  - [Andrologic problems in prostatic carcinoma].
AB  - In our opinion, the attempt to save the sexuality and the erectile ability in a
      patient with a prostate cancer, in the respect of an absolute oncological
      radicality, should be recommended since potency represents for the patient a
      primary aspect in the quality of residual life. At the Institute of Urology of
      the University of Milan a study to identify pathogenetic mechanisms leading to
      erectile failure in the various phases of a prostate cancer was performed. From
      January 1988 to December 1993, 36 patients (range 50-60 years old) suffering from
      prostate cancer B1 stage (14 pts), B2 (20 pts) and C (2 pts) underwent to radical
      prostatectomy. Out of 24 pts reporting erectile ability before surgery, 10 was in
      B1 stage and underwent monolateral nerve-sparing technique. Out of these, 6 pts
      (60%) maintained the erection after the operation. The treatment with LHRH
      analogues weighted on loss of libido and erectile and erectile potent due to
      central androgenic delete. At our Institute 87 pts in treatment with LHRH
      analogues reported loss of erection in 80% of cases. In this group 22 underwent
      to an andrological examination. The exams (Dynamic penile Doppler, Dynamic
      Cavernosometry and stimulating test with intracavernous vasoactive drugs) confirm
      the absence of peripherical damages in the pathogenesis of the erectile
      dysfunction. Patient underwent radiotherapy develop a secondary impotence due to
      an obliterant progressive angioitis in a percentage ranging from 30 to
      80%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252081
TI  - [Intervention models in andrology in adult-elderly patients with psychogenic
      erectile dysfunction].
AB  - The Authors deals of the principal models of management in andrologic ambit on
      patients adult-elder affected by psychogenic impotence. Yet they made a critic
      remark of these models and show a different management model named "within
      treatment". The authors presents the results achieved using this model in the S.
      Luigi Gonzaga Hospital surgery for male sexual diseases.

PMID- 8252082
TI  - [Andrologic therapy in the elderly--therapy seeking, acceptance, risks,
      satisfaction].
AB  - The paper discusses over questions and hidden requests of andrological and
      sexological help in the general medical consultation of the elderly; the most
      frequent specific andrological symptoms and the pertinent sexological
      implication; the conscious and unconscious ambivalence present in the acceptance
      of therapy; ongoing risks, in case of inappropriate or inadequate evaluation of
      the therapeutic request.

PMID- 8252083
TI  - [Sexual behavior in the elderly].
AB  - With the improvement of quality life in the elderly of technologically developed
      countries, sexuality has become an important aspect of aging. In the elderly
      there is a progressive decline of organic functions; the decrease of sexual and
      procreating activity is linked with the impaired male hormonal production. The
      four stages of sexual function are modified: 1. delayed erection; 2. plateau
      prolongation; 3. orgasm modifications; 4. fast penis detumescence. In addition to
      organic impairment, aesthetic, social, environmental and psychological factors
      can restrict sexual activity, as well as past sexual experiences and co
      morbidity. There are specific aspects concerning sexuality in the elderly, such
      as the increased chances of public relations and emotional involvement, the more
      intense psychic activity and the stronger process of removal and sublimation of
      impulses. In conclusion the best way to deal with sexuality in the elderly is the
      multidimensional assessment.

PMID- 8252084
TI  - [Familial multiple bilateral carcinoma of the kidney: clinical strategy and
      surgical approach].
AB  - A case of familiar bilateral multicentric RCC in a young woman is an ideal model
      to evaluate preoperative and intraoperative diagnostic and surgical tools in
      order to achieve two distinct goals: the oncologic radicalness and the renal
      function preserved. Radical bilateral nephrectomy, the renal hypothermia by
      perfusion of both kidneys, the bench high resolution sonography of parenchyma,
      the choose of one kidney suitable for conservative surgery, the resection of
      suspect lesions with intraoperative pathology, the reconstructive bench surgery,
      the autotransplantation, are the steps accurately performed with particular
      concern to eradication of all the tumoral lesions present in the kidneys. The
      results confirm that renal function has been preserved with this method.
      Radicalness should be appointed by a longlasting follow up. However, as it is
      discussed, conservative surgery, when accurately performed can give results not
      different from radical demolitive surgery. In this paper tools to improve
      diagnostic and therapeutic methods are described in order to increase the
      diagnostic accuracy and the therapeutic efficacy. The possibility that this
      multiple RCC can be a part of the abnormalities occurring in the Von Hippel
      Lindau syndrome does not change the surgical approach, being the RCC the worst
      prognostic factor of the syndrome.

PMID- 8252085
TI  - [Treatment of prostatitis with a new laser probe with optic fiber].
AB  - The present treatment of the subacute abatteric prostatitis, prostatodinia,
      prostatosis (the most common prostatic flogistic diseases) is represented by the
      transrectal applications of infrared Laser. The concrete opportunity of applying
      such an energy directly to the prostate in cases of flogistic diseases--a very
      frequent pathology treated in many different and controversial ways--is a
      stimulating therapeutical method which we tested and that we presently use in our
      clinics. The thanks to the realization of an high technology equipment, easy to
      handle, cheap, safe, perfectly suitable, formed by a new infrared Laser probe,
      transrectal, atermical, made by a optical fibre, which we present. Micturition,
      ejaculation, fertility may draw a relevant improvement, provided that the same
      treatment is performed after a specific medical diagnosis and following a strict
      protocol.

PMID- 8252086
TI  - Perineal biofeedback versus pelvic floor training in the treatment of urinary
      incontinence.
AB  - Perineal floor training and perineal biofeedback allow to reach a good
      improvement of clinical discomfort in the treatment of stress and urge urinary
      incontinence. The aim of this study is the real evaluation of the benefit due to
      a 6 week perineal biofeedback and pelvic floor training (PFT) versus PFT alone. 8
      female patients have been treated with a 6 week trial with perineal biofeedback
      plus PFT trial and 22 with a 3 month PFT alone one. PFT alone, permits a good
      improvement but 10% less than if associated to perineal biofeedback.

PMID- 8252087
TI  - Treatment of adult primary uncomplicated nocturnal enuresis by pelvic floor
      training and behaviour modification therapy.
AB  - A therapeutical trial based on pelvic floor training, reduced evening fluid
      intake and a 3 hour nocturnal awakening has been performed by 12 adult primary
      enuretics. The aim of this study is to verify if diurnal pelvic floor training is
      useful to gain a nocturnal micturition control.

PMID- 8252088
TI  - [Vesico-urethral and entero-urethral anastomosis: anatomo-surgical considerations
      and technical note].
AB  - Following radical prostatectomy or radical cystectomy with orthotopic ileal
      bladder (in male patients), the cervico-urethral or entero-urethral anastomosis
      are at high risk for urinary stress incontinence, due to the shortening of the
      urethral functional length as well as "unavoidable downward fall" of the perineum
      after sectioning of the anterior portion of the sacro-pubic ligaments. That
      descensus of the perineum, if uncorrected, might cause a functional
      extraabdominal positioning of the residual functional urethra; this feature is
      close similar to one of the most important pathogenetic factors of genuine stress
      incontinence in the female. In order to correct that perineal fall is advisable
      to perform the so-called "secondary sphincter" (after Rocca Rossetti, 1982) by
      suturing with the same stitches not only the anastomotic edges but the medial
      part of the levator ani (i.d. pubo-rectal muscles) and the retro-urethral
      striated musculature as well; this technique ensure a good intraabdominal
      position of the residual functional urethra and prevents dangerous tensions on
      the anastomosis. The Authors stress the importance of a delicate dissection of
      the prostatic apex with no or minimal manipulation of the membranous urethra
      avoiding to evaginate it from the surrounding pelvic floor, that could damage its
      vascular supply. Following the before mentioned criteria the Authors performed 17
      radical prostatectomies and 7 ileal bladder after radical cystectomy with
      satisfactory results (4.1% of postoperative urinary incontinence).

PMID- 8252089
TI  - [Melatonin secretion in Klinefelter's syndrome].
AB  - It has been observed that the pineal gland seems to modulate diencephalic
      neuroendocrine activity through its principal hormone, melatonin. In animals,
      melatonin inhibits the secretion and release of hypophyseal gonadotropins,
      probably by inhibiting hypothalamic releasing factors; in man, on the contrary,
      the administration of LHRH seems to have a stimulating effect on melatonin serum
      levels. In the light of this, in pathologies characterised by an imbalance in the
      hypothalamus-hypophyseal-gonad axis, it is possible to hypothesise variations in
      the secretion of melatonin and/or in its circadian fluctuations. In order to
      clarify further the relationship between the epiphysis and the hypothalamus
      hypophyseal axis, the present study evaluated the pattern of melatonin secretion
      in a group of 16 patients with Klinefelter's syndrome. The circadian rhythm of
      melatonin secretion was determined from venous blood samples taken at 9 am, 1 pm,
      5 pm, 9 pm, 1 am and 5 am; the same protocol was also followed in two control
      groups of respectively prepuberal and puberal healthy subjects. During the night
      samples were taken as rapidly as possible, using a red light source in order to
      not interfere with melatonin secretion. All of the examinations were performed
      during the winter period. Serum levels of melatonin were determined, after
      extractions with diethylether, by means of a double antibody RIA using
      commercially available kits (Bioscience Product--The Netherlands). Intra- and
      inter-assay coefficients of variation were respectively 3% and 8%. The data are
      reported as mean values +/- SD; the results were analysed by means of Student's
      test for unpaired data and analysis of variance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252090
TI  - [Negative feedbacks in the pathogenesis of primary arterial hypertension: the
      mechanical sensitivity of the endothelium].

PMID- 8252091
TI  - [The mechanisms of the development of arterial hypertension with a calcium
      deficiency in the diet].
AB  - The arterial pressure was significantly higher in the calcium-deficient group of
      rats as compared with the normal rats: 150 +/- 7 and 116 +/- 2 mm Hg, resp. The
      first group of animals had a hypertensive factor in the blood. The hypertensive
      activity of the calcium-deficient animals was associated with no known pressor
      agents and was rather similar to Pang's hypertensive factor. The latter was also
      found in some patients with essential hypertension.

PMID- 8252092
TI  - [The hypertensive reactions during endothelin exposure on the structures of the
      ventrolateral medulla oblongata].
AB  - Administration of endothelin induced a hypertensive response in anesthetised
      cats. The mechanism of this response seems to involve an augmentation of the
      resistance of peripheral vessels due to enhanced descending sympatho-activating
      influences.

PMID- 8252093
TI  - [A comparative evaluation of the hemodynamic parameters and of the vascular
      adrenergic reactions in the skeletal muscles of normo- and hypertensive rats].
AB  - In normotensive and hypertonic rats of the WKY and SHR lines, resp., a
      significant difference between values of the resistance against blood flow was
      found: it was 1.34 and 1.5-fold greater in the latters for the regimens of
      constant perfusion pressure and stabilised blood flow, resp. The capillary
      hydrostatic pressure and the capillary filtration coefficient did not differ
      significantly in both groups. The increase of the vascular resistance in skeletal
      muscles in response to noradrenaline administration was significantly lesser in
      the hypertensive rats. The data obtained suggest that the extent of
      distensibility of the vascular bed by the blood pressure can be a determining
      factor of the adrenergic shift of vascular resistance in both groups of animals.

PMID- 8252094
TI  - [The role of the endothelium-derived relaxing factor in regulating the
      distensibility of the vessels of the arterial bed].
AB  - The inhibiting agent N-nitro-L-arginine was shown to constrict the hindlimb
      arterial vessels and to decrease their distensibility in the cats with the
      synthesis of the endothelial relaxing factor. Acetylcholine exerted an opposite
      effect. The EDRF system seems to have a tonic activity whereas some unrelated
      factors are involved in the acetylcholine effect.

PMID- 8252095
TI  - [An automated system for measuring and processing physiological information].

PMID- 8252096
TI  - [An improved method for measuring the blood pressure of rats].

PMID- 8252097
TI  - [A bibliographic index of the Soviet literature for 1970-1990 on the problem of
      the mechanisms of the formation of arterial hypertension].

PMID- 8252098
TI  - [Arterial hypertension in emotional stress: the neural and humoral mechanisms of
      its prolongation].

PMID- 8252099
TI  - [The significance of rhythmic contractile activity of the arteries for the
      regulation of the rate of blood flow].
AB  - The effect of rhythmic contractile activity of the rat mesenteric arteries upon
      the blood flow velocity, was studied. The vasomotion was induced both by a direct
      stimulation of vascular motor nerves and a nociceptive stimulation. The wave of
      the vasomotion was shown to spread towards the periphery of the arterial bed
      irrespective of the way of influencing. The mathematical model of the vessel as a
      peristaltic pump working against the background of a constant shifting of the
      pressure with the contraction wave's parameters measured during the experiments,
      revealed that the blood flow velocity equally depended on the amplitude and the
      velocity of spreading of the rhythmic contractions. The experiments suggest
      involvement of the sympathetic nervous system in the control of the vasomotion's
      parameters and, consequently, of the blood flow velocity in the vessels during
      latters' rhythmic contractile activity.

PMID- 8252100
TI  - [The effect of captopril on the arterial pressure, structural resistance and
      vascular reactivity of the kidney in rats with nephrogenic hypertension].
AB  - The angiotensin-converting enzyme inhibiting agent captopryl suppressed a
      moderate hypertension in rats with pyelonephritis and with ureteral obstruction,
      but not in rats with ureteral obstruction combined with the renal artery
      constriction. The suppression of the hypertension was accompanied by a reversion
      of structural alterations in the blood vessels.

PMID- 8252101
TI  - [The effect of arterial pressure pulsations on the resistive function of the
      vessels in different organs and species and with differing initial tonus].
AB  - In normotensive rabbits, normo- and hypertensive rats, an increase of the pulse
      amplitudes from 0-10 to 70-80 mm Hg at a constant value of the mean pressure in
      magistral arteries in the skeletal muscles and skin, induced a decrease of the
      resistance against blood flow due to occurring vasodilation. The response in the
      SHR was considerably lesser than in normotensive animals. The vasodilation
      occurring in some organs and tissues to dynamic deformation of the blood vessels
      by the pulse pressure seems to play a significant role in the adaptive responses
      of the circulation system to ambient stimuli activating the heart output. This
      response seems to be weakened under conditions of developed arterial
      hypertension.

PMID- 8252102
TI  - [The effect of a psychoemotional load on the activity of the sympathetic-adrenal
      system in subjects with different levels of arterial pressure].
AB  - Subjects with initially increased level of arterial pressure were shown to have a
      higher contents of vasopressin in the blood plasma and of cortisol in the saliva.
      All the subjects revealed an increased systolic and diastolic blood pressure in
      response to a psycho-emotional load. The levels of cortisol and vasopressin did
      not increase at that. Neither the adrenaline level changed whereas the
      noradrenaline level increased. The latter increased more in the subjects with a
      milder form of arterial hypertension. The data obtained suggest that the
      reactivity of the sympatho-adrenal system is higher in the subjects with an
      increased arterial pressure.

PMID- 8252103
TI  - [Na, K-ATPase activity in the erythrocyte membrane preparations and kidneys of
      spontaneously hypertensive rats].
AB  - The enzyme activity in the cortex and medulla of the SHR was 1.5-2.0-fold lower
      than that of the WKY and Wistar rats. The Na, K-ATPase and Ca-ATPase activities
      were by 25 and 15% lower in the erythrocyte ghosts of the SHR than in
      normotensive rats. Removal of protein of the membrane skeleton from the
      erythrocyte membranes abolished the difference in the enzyme activity of normo-
      and hypertensive rats. The lower Na, K-ATPase activity in the SHR kidney seems to
      be an etiological factor in development of primary hypertension.

PMID- 8252104
TI  - [The hypothalamic mechanisms of the development of arterial hypertension in old
      age].
AB  - The electrical activity of hypothalamic nuclei was found to change in accordance
      with changes in arterial blood pressure in old rabbits with reflexogenic
      hypertension. Stimulation of the hypothalamus induced an obvious increase in the
      blood pressure, considerable changes in cardiac activity, coronary insufficiency
      occurrence and alteration of the myocardium structure. An increase in
      excitability of the pressor structures of the anterior and posterior hypothalamic
      areas occurred with ageing. The age-induced changes in the hypothalamus could be
      either the primary mechanisms of development of hypertension, or they can be
      involved at later stages of the hypertension pathogenesis.

PMID- 8252105
TI  - [The Ca2(+)-binding capacity of the thrombocytes in rats with hydrocortisone
      induced steroid hypertension].
AB  - The Ca(2+)-binding ability of the thrombocytes' membranes did not change within
      30 min after administration of hydrocortisone when no significant changes of
      arterial pressure occur. In stable increase of arterial pressure evoked by thrice
      repeated administration of hydrocortisone, a redistribution of the intracellular
      Ca2+ occurs: its contents decreases at the external plasmatic membrane and
      increases in intracellular membranes. The hypertensive response seems to coincide
      with the redistribution. The same mechanisms of Ca2+ metabolism disorders seem to
      underlie both essential and steroid hypertension. The cell's adrenoreceptor
      mechanisms are probably involved in the process.

PMID- 8252106
TI  - [The reactivity of the skin vessels in arterial hypertension].

PMID- 8252107
TI  - [The chronotropic reaction and the dynamics of the blood supply to the forearm
      during modulation of the baroreceptor reflex activity in patients with arterial
      hypertension].
AB  - Original method of baroreflex activation and deactivation was described.
      Bradycardia and vasodilatation of the forearm vessels were observed at baroreflex
      activation. Tachycardia and forearm blood flow reduction were observed at
      baroreflex deactivation. The sensitivity of baroreflex heart component vas shown
      to depend upon the arterial pressure and a baseline cardiac cycle duration in
      both normo- and hypertensive subjects.

PMID- 8252108
TI  - Bone mass measurement: how, where, when and why?
AB  - Low bone mass, by far the major causal factor in osteoporotic fractures, cannot
      be predicted from the clinical evaluation of risk factors for osteoporosis.
      Measurement of bone mass is commonly achieved by using dual-energy X-ray
      absorptiometry (DXA), which has replaced dual-photon absorptiometry (DPA); single
      energy X-ray absorptiometry (SXA), which is likely to replace I-125 single-photon
      absorptiometry; and by using quantitative computed tomography (QCT). Measurement
      of ultrasound speed and attenuation across the calcaneum is another promising
      method still under investigation. Each method may have some advantage or
      disadvantage relating to practical aspects (cost, scanning time, availability)
      and technical aspects (radiation dose, accuracy, precision). Several clinical
      situations have been identified in which measurement of bone mass will be useful,
      including women after the menopause to select those who should receive bone
      sparing agents, and patients with x-ray vertebral deformity to confirm the
      diagnosis of osteoporosis. DXA allows measurement of bone mass at different
      skeletal sites, including the lumbar spine (by anteroposterior and lateral view),
      the hip, the forearm, and the total skeleton. The choice of the site to be
      screened will often be dictated by clinical considerations such as age and
      associated osteoarthritis, but, in theory, should be oriented by the ability of
      bone mass measurement at each site to predict osteoporotic fractures. Several
      prospective studies have shown that a decrease of 1 standard deviation of bone
      mass is associated with a 1.5- to 3-fold increase of the relative risk of
      fracture. Measuring any site is probably equally predictive of the risk of all
      osteoporotic fractures, while measurement of the hip appears to be a better
      predictor of the risk of hip fracture.

PMID- 8252109
TI  - Peak bone mass, a growing problem?
AB  - The focus of attention in osteoporosis research has been on factors influencing
      bone fragility and the propensity for trauma (falls) during adulthood and old
      age. The purpose of this review is to change the focus of this attention toward
      consideration of skeletal growth in the first 20 years of life and to demonstrate
      the importance of mineral accrual (and the factors influencing this accrual) in
      determining bone density in adulthood and old age. We suggest that the
      epidemiology of fractures may be unified by a central role of reduced peak bone
      density in the pathogenesis of the low bone density found in patients with
      fractures. The reduced peak bone density establishes the relevance of age-related
      and sex hormone-dependent bone loss. Risk and protective factors in the first 20
      years of life may have quantitatively larger, and qualitatively different effects
      on the axial and appendicular skeleton than exposure during adulthood. Public
      health measures focussed on optimising mineral accrual in the first 20 years of
      life may be more important than health care measures more proximate to the age at
      which fractures occur.

PMID- 8252110
TI  - Bone mass among premenopausal women.
AB  - Bone mass in early adult life, or peak bone mass, is primarily under genetic
      control, although recent data suggest that alterations in nutrition and life
      style during growth may modify the genetic potential. Cross-sectional data
      indicated that upon completion of growth, there was a period of skeletal
      consolidation that resulted primarily from increased width of cortical bones.
      Data on cancellous bone are conflicting. Cross-sectional data suggest that
      cancellous bone mass reaches a maximum at about age 18 years. Bone mass in the
      spine appears stable until the beginning of menopause, unless there are other
      disturbances of ovarian function. On the basis of cross-sectional data,
      significant bone loss in the femoral neck in premenopausal women appears to occur
      prior to changes in ovarian function. This decline in hip density is also
      independent of body size, nutritional influences, or other variables thought to
      influence bone mass. Longitudinal data are not available to confirm the reduction
      in femoral neck bone mass. Preliminary data indicate that modest disruptions of
      ovarian function, insufficient to result in frank amenorrhea, might impact
      negatively on bone mass. A detailed longitudinal study of menstrual and other
      factors controlling bone mass in premenopausal women is needed. If bone mass can
      be modified, ensuring a maximal skeletal mass becomes a viable possibility for
      prevention of osteoporosis.

PMID- 8252111
TI  - Postmenopausal bone loss: does HRT always work?
AB  - In a 3-year study comparing oral and transdermal HRT, we measured bone density in
      the spine and proximal femur by dual-photon absorptiometry. Sixty-six women were
      randomly allocated to receive either oral conjugated equine oestrogens, 0.625 mg
      daily, together with cyclical oral dl-norgestrel, 0.15 mg daily, or transdermal
      17 beta-oestradiol, 0.05 mg daily, together with cyclical transdermal
      norethisterone acetate, 0.25 mg daily. We found that only 2% showed significant
      vertebral bone loss on either treatment, whilst approximately 12% lost from the
      proximal femur. Compliance was demonstrated by monitoring all used patches and
      pill packets, recording all side effects and bleeding patterns, and by the
      demonstration of appropriate changes in levels of gonadal steroids and
      lipoproteins. Comparing the bone losers with the ten highest gainers, lowers were
      closer to their menopause but were not different in body mass or life style.
      Serum oestradiol levels were similar, and both groups showed a similar response
      in terms of changes in bone biochemical markers and lipoproteins in response to
      HRT. In thus seems that a small proportion of women do not conserve bone density
      in the proximal femur with standard doses of HRT. It remains to be determined
      whether they could be identified by more specific biochemical markers of bone
      turnover, and whether they would maintain with a higher dose of oestrogen.

PMID- 8252112
TI  - Bone mass and bone loss in the elderly: a special case?
AB  - Elderly women and men lose bone at a rate of < or = 1% per year. This results in
      an increasing risk of most fractures, of which hip fractures account for the
      greatest proportion of death, disability, and medical costs. Falls are the
      immediate precipitating factor for about 90% of hip fractures and 80% of other
      types of fractures in women. Since the rate of bone remodeling increases with
      age, antiresorptive therapies are likely to be at least as effective in the
      elderly as in younger adults. Calcium supplementation, for example, slows bone
      loss more effectively in older women than in those within 5 years of menopause,
      although the effectiveness of calcium for prevention of fractures remains
      uncertain. Vitamin D deficiency is more common in the elderly, and
      supplementation of deficient women appears to slow bone loss, at least during
      winter. Calcium plus vitamin D may substantially reduce the risk of hip fracture
      in the frail elderly. A randomized trial showed that estrogen remains effective
      in preventing vertebral fractures in older women. There is no reason to believe
      that the effectiveness of other agents would diminish with age. Preventive
      therapy offers greatest and most immediate benefit to those who have the highest
      risk of fracture: the elderly, those with previous fractures, those at increased
      risk of falling, and those with lowest bone mass. Since the relationship between
      bone mass and risk of fracture remains strong in elderly women, bone mass
      measurements may also be as useful in the elderly as in younger adults.

PMID- 8252113
TI  - How feuding hospitals joined hands to serve their community. Interview by Kathryn
      Taylor.

PMID- 8252114
TI  - Gaining ground where it counts.

PMID- 8252115
TI  - Leaders analyze Clinton plan, piece by piece. HMOs & reform.

PMID- 8252116
TI  - Facilities planning: 10 steps for changing times.

PMID- 8252117
TI  - Patience & partnership. Health systems cultivate two ingredients to create
      healthier communities.
AB  - With most health care reform proposals calling for a reconfigured delivery system
      aimed at making health status improvements, the ability to form
      provider/community partnerships may become a core capability for providers in
      communities of all types. But a number of barriers must continually be faced,
      including lack of trust, crumbling infrastructures, scarcity of funding, cultural
      issues, and others. A look at the "hows" and "whys" behind this crucial area for
      provider initiatives.

PMID- 8252118
TI  - Clinical contracting moves into managed care.

PMID- 8252119
TI  - Survey on PHOs reveals surprises. Good news, bad news.

PMID- 8252120
TI  - The quality march. Part two of a national survey of quality improvement
      activities.
AB  - Overall, the findings suggest that CQI/TQM hospitals report a greater level of
      satisfaction with their quality improvement efforts; take more board actions to
      improve quality; perceive a more positive impact on human resource development
      issues and on financial outcomes; are generally more likely to report
      statistically significant improvements in selected patient outcomes; and are more
      likely to report cost savings than hospitals not involved in CQI/TQM activities.
      The final article in the series will discuss CQI/TQM areas of assistance in
      furthering quality improvement efforts, particularly in regard to clinical
      applications and physician involvement.

PMID- 8252121
TI  - Cincinnati. Major employers call the shots on health care delivery.

PMID- 8252122
TI  - Paul Ellwood. Managed competition visionary. Interview by Mark Hagland.

PMID- 8252123
TI  - Public hospitals and reform: manageable competition.

PMID- 8252124
TI  - Health care reform and hospital downsizing: facing new realities.

PMID- 8252125
TI  - A framework for the continual improvement of health care: building and applying
      professional and improvement knowledge to test changes in daily work.
AB  - We seem to lack a well-defined, comprehensive, and shared understanding of what
      is required for the continual improvement of health care--at the organizational
      and the industry levels. This article presents a framework that defines the new
      body of knowledge which, when joined with the professional knowledge of health
      care workers, can make continual improvement possible; and gives requirements for
      building and applying this knowledge to bring about improvement in health care
      organizations.

PMID- 8252126
TI  - Asking effective questions: an important leadership role to support quality
      improvement.
AB  - Effective questions stimulate, guide, and empower employees to think critically
      about the improvement processes that they are involved in as team leaders or team
      members in their daily activities. Learn how questions must be carefully phrased
      in order to provide guidance and maintain the integrity of the team's ability to
      choose options and implement change.

PMID- 8252127
TI  - Information technology applications in quality assurance and quality improvement,
      Part II.
AB  - Many information technologies have been or could be applied to efforts to measure
      and improve health care quality. This article reviews the recent literature in
      medical informatics, quality assurance, and quality improvement to identify these
      and current, emerging, and potential technologies.

PMID- 8252128
TI  - Developing a patient measurement system for the future: an interview with Eugene
      C. Nelson.
AB  - In this interview, Eugene C. Nelson, provides organizations with a systematic
      strategy for tying feedback on patient needs and expectations to ongoing
      performance improvement efforts. He also takes a look at the future and provides
      organizations with a glimpse of what to expect in the next five years.

PMID- 8252129
TI  - Performance-based hospital contracting for quality improvement.
AB  - A carefully negotiated process that ties improvements in performance to
      additional compensation can align incentives and support efforts to improve care.
      Such a process needs to be objective, data-driven, and focused on issues that are
      important both to the purchaser and to the provider.

PMID- 8252130
TI  - Information technology applications in quality assurance and quality improvement,
      Part I.
AB  - Many information technologies have been or could be applied to efforts to measure
      and improve health care quality. This article reviews the recent literature in
      medical informatics, quality assurance, and quality improvement to identify these
      and current, emerging, and potential technologies.

PMID- 8252131
TI  - Slang 'on board'. A moral analysis of medical jargon.
AB  - Medical jargon is commonly used by health-care professionals. The use of such
      jargon is sometimes criticized as insensitive or callous. Rather than generalize,
      we identify four basic types of medical jargon and discuss their relevant moral
      distinctions. Our characterizations of jargon include medical acronyms,
      euphemisms, and initiatory and derogatory language. Physicians should be aware of
      the ways in which they use medical slang. Jargon can serve useful purposes but
      its moral status is often dependent on the function it serves and the context in
      which it is used. Jargon that is clearly derogatory can reflect negatively on the
      moral character of the medical profession and should be avoided when possible.

PMID- 8252132
TI  - American Medical Association Diagnostic and Treatment Guidelines on Child Sexual
      Abuse.
AB  - Intrafamilial child sexual abuse is a manifestation of a dysfunctional family.
      The physician should focus on assessment of the immediate safety and long-term
      best interests of the child as well as on protection of the child from further
      harm.

PMID- 8252133
TI  - Men sexually abused in childhood. Sequelae and implications for the family
      physician.
AB  - Although the majority of childhood sexual abuse victims are women, male children
      are also at risk for sexual assault and consequent long-term effects including
      major psychiatric disorders, substance abuse, sexual dysfunction, and
      somatization syndromes. Male patients sexually abused in childhood or adolescence
      may present to the primary-care physician with specific interpersonal or
      developmental crises or with persistent depression, anxiety, or somatic
      complaints. The physician can serve a therapeutic role by validating the
      patient's experience and can provide the patient with information on the
      prevalence and consequences of male sexual abuse. Assessment of the impact of
      sexual abuse will rely on the sensitive and systematic evaluation of critical
      variables related to the abuse. More severely traumatized patients will require
      assessment for suicide potential and referral for mental health services.

PMID- 8252134
TI  - Responses of health care professionals to proposed mandatory HIV testing.
AB  - OBJECTIVE: to survey active health professionals to assess the response to and
      impact of a mandatory human immunodeficiency virus (HIV) testing policy on health
      care providers and the communities in which they practice. DESIGN AND SETTING:
      Anonymous four-page survey of active health professionals at 13 hospitals in
      northern and central New Jersey. PARTICIPANTS: 1557 physicians and nurses
      responded to the survey. Response rate was approximately 41%. INTERVENTION:
      Hypothetical intervention. MAIN OUTCOME MEASURES: Responses to a series of
      questions relating to a hypothetical mandatory HIV testing policy for health
      professionals. RESULTS: Approximately three fourths of all surveyed health
      professionals stated that a mandatory testing policy would persuade individuals
      in their profession not to work in high-prevalence areas. Among those who
      currently work in high-prevalence HIV/acquired immunodeficiency syndrome (AIDS)
      areas, only 51% said that they would definitely or probably remain in that area
      should such a policy be instituted. Among those practicing surgery or performing
      invasive procedures, 7% currently avoid HIV-positive patients, and an additional
      34% said that they would do so under the proposed testing policy. Finally, 4% of
      these professionals currently advice others to stop working in high-prevalence
      areas, and an additional 22% state that they would definitely do so if the
      proposed policy were instituted. CONCLUSIONS: If physicians and nurses behaved in
      accordance with their survey responses, institution of a mandatory HIV testing
      policy would create a shortage of physicians and nurses in high-prevalence
      HIV/AIDS areas.

PMID- 8252135
TI  - Is anybody talking to physicians about acquired immunodeficiency syndrome and
      sex? A national survey of patients.
AB  - OBJECTIVE: We wanted to know what proportion of the US population had spoken with
      a physician about sex and the acquired immunodeficiency syndrome (AIDS). In
      particular, we wanted to know whether patients who were at risk for sexually
      transmitted diseases, including human immunodeficiency virus (HIV), had had such
      discussions. DESIGN: A telephone survey of a US nationwide random probability
      sample of adults was conducted in the summer of 1991. PATIENTS: The survey was
      completed by 1350 adults; of these, 1312 were patients, defined as those who
      reported that they had been to a physician within the last 5 years. MAIN OUTCOME
      MEASURE: We assessed whether patients reported having had discussions about sex
      and AIDS with physicians. RESULTS: Only 259 (20%) of patients in our survey
      reported that they had talked with a physician about AIDS. Fifty-five (21%) of
      those who had talked with a physician about AIDS reported that the physician
      started the discussion. Few patients reported that they had spoken with a
      physician even when it appeared vital that they do so: 46 (26%) of those who
      reported that their chances of getting the AIDS virus were "high" or "medium" and
      25 (23%) of those who reported being at behavioral risk for AIDS had spoken to a
      physician about AIDS. CONCLUSIONS: Few patients reported having discussed sex and
      AIDS with a physician, even if the patients considered themselves to be at risk
      for contracting HIV or another sexually transmitted disease. More of these
      discussions must take place to prevent the spread of sexually transmitted
      diseases and AIDS and to facilitate testing and early treatment of HIV-infected
      individuals.

PMID- 8252136
TI  - Reflections after 9 years of working with patients with acquired immunodeficiency
      syndrome. What I have learned.

PMID- 8252137
TI  - Mifepristone (RU 486).

PMID- 8252138
TI  - RU 486. The progesterone antagonist.
AB  - The objective of this report is to review the current and potential therapeutic
      uses of the progesterone antagonist drug RU 486 (mifepristone). Publications
      cited in peer-reviewed journals were identified through a search of the Index
      Medicus from 1987 through 1992. A wide range of research reports was reviewed,
      including human, animal, and tissue culture experiments. Data from published
      reports were included in this report if they addressed the mechanism of action,
      clinical indications, and potential uses for RU 486. The review disclosed that as
      a progesterone antagonist, RU 486 is clinically effective for inducing first
      trimester abortions, for ripening and dilating the cervix to facilitate
      intrauterine surgical procedures, and as a postcoital contragestational agent. As
      a glucocorticoid antagonist, RU 486 is useful for treating inoperable cases of
      nonpituitary Cushing's syndrome. RU 486 is under investigation for use as an
      antineoplastic agent; it has shown promise as a treatment of meningioma, breast
      cancer, prostate cancer, and hepatoma. RU 486 may also have a role in the
      treatment of endocrinologic conditions such as endometriosis and premenstrual
      syndrome. I conclude that RU 486 is effective and in current clinical use for a
      number of reproductive indications and for treatment of Cushing's syndrome. The
      drug also has potential as therapy for certain neoplasms and endocrinologic
      conditions.

PMID- 8252139
TI  - The etiologic features of depression in adults. Council on Scientific Affairs,
      American Medical Association.
AB  - Over the past 30 years, considerable advances have been made in understanding the
      origin of depression. The explosion of knowledge includes studies on genetics,
      animal models of depression, neurotransmitter and neuroendocrine studies, and
      psychological and sociological risk factors. Depression, like other medical
      illnesses, presents with a wide spectrum of syndromes and severity. Most
      clinicians support a risk factor model that reflects the varying contributions of
      biological (including genetic), psychological, and environmental factors. This
      article reviews the research on the etiologic factors in depression.

PMID- 8252140
TI  - A review of Iliad and Quick Medical Reference for primary care providers. Two
      diagnostic computer programs.
AB  - Two diagnostic computer programs, Iliad (Applied Informatics Inc, Salt Lake City,
      Utah) and Quick Medical Reference (Camdat Corp, Pittsburgh, Pa), are commercially
      available. Both describe a large subset of internal medicine diseases. These
      programs, also called knowledge bases, have different structures and diagnostic
      methods and emphasize somewhat different experimental observations regarding
      problem solving and expert diagnostic behavior. Quick Medical Reference has more
      diverse reference features and emphasizes diagnostic competitors (diseases that
      explain similar features in a case). Iliad has better developed teaching features
      and emphasizes a probabilistic approach. The histories and methods of these
      programs place various constraints on their diagnostic capabilities, especially
      from a primary care perspective. Although neither program is currently likely to
      fill the role of an expert diagnostic consultant for a family practitioner, both
      have potential as unique reference and teaching tools in primary care.

PMID- 8252141
TI  - Revolution in practice management: a new kind of drudgery.

PMID- 8252142
TI  - Welcome to the family, more than 'referralists'.

PMID- 8252143
TI  - Science advocacy. A role for the family practitioner.

PMID- 8252145
TI  - Cervical cancer screening. Issues of collection tools and reporting.

PMID- 8252144
TI  - Does the system of Papanicolaou test nomenclature affect the rate of referral for
      colposcopy? A survey of family physicians.
AB  - OBJECTIVE: To determine whether a new system of Papanicolaou test nomenclature
      (the Bethesda system) or other physician variables influence recommendations for
      colposcopy and biopsy for women with borderline to moderately abnormal
      Papanicolaou test results. We hypothesized that physician demographic and
      practice variables, in addition to Papanicolaou test nomenclature, would
      influence recommendations for colposcopy. DESIGN: A survey was mailed to a random
      sample of 510 active members of the American Academy of Family Physicians.
      PARTICIPANTS: Three hundred thirty-five (66%) of the eligible physicians
      responded, representing all 50 states. Of those in active practice, 78% were in
      private practice, with a mean age of 44 years and a mean time in practice of 10
      years. Ninety-three percent of respondents in active practice performed
      Papanicolaou tests. MAIN OUTCOME MEASURE: Rates of recommendation for colposcopy
      and biopsy in response to abnormal Papanicolaou test reports framed by a single
      clinical scenario. RESULTS: Physicians recommended colposcopy more often when the
      Bethesda nomenclature system was used to describe the results of the Papanicolaou
      test. These differences were significant for four specific Papanicolaou smear
      pairs. Inclusion of recommendations for further evaluation strongly influenced
      physicians to recommend colposcopy. In multivariable analyses, demographic and
      practice variables were not associated with recommendations for colposcopy.
      CONCLUSIONS: The Bethesda system of nomenclature, when compared with a
      traditional descriptive nomenclature system, influenced family physicians to
      recommend colposcopy and biopsy more often for abnormal Papanicolaou test results
      presented in a clinical scenario. Greater utilization of technology and higher
      medical care costs may result from use of the Bethesda system. Guidelines for
      evaluation of abnormal Papanicolaou test results are needed for use in
      conjunction with the Bethesda system guidelines for Papanicolaou test reports.

PMID- 8252146
TI  - Cryotherapy precision. Clinician's estimate of cryosurgical iceball lateral
      spread of freeze.
AB  - OBJECTIVE: To examine physicians' ability to estimate the lateral spread of
      freeze (LSF) of a cryosurgical iceball using three techniques. DESIGN: A
      nonrandomized control trial of in vitro nitrous oxide cryosurgical procedures.
      SETTING: Primary care residency training programs. PARTICIPANTS: A convenience
      sample of 80 resident and faculty physicians from four family practice residency
      programs and one obstetrics and gynecology residency program. INTERVENTIONS:
      After performing cryosurgery with standard naked-eye and colposcopic-assisted
      techniques, subjects used a new experimental cryosurgical iceball gauge (CIG) to
      estimate the LSF during cryotherapy. MAIN OUTCOME MEASURES: LSF estimations
      reported physicians were compared simultaneously with those measured by an
      observer. RESULTS: The mean (+/- SD) LSF estimation errors at the termination of
      freeze were as follows: 2.62 +/- 2.42 mm for the colposcopy technique, 2.00 +/-
      2.16 mm for the naked-eye method, and 1.28 +/- 0.87 mm for the CIG technique. The
      range of maximum error was 6.5 to 11 mm for the colposcopic technique, 5.5 to
      12.5 mm for the naked-eye method, and 3.0 to 4.0 mm for the CIG technique.
      CONCLUSIONS: Overestimation of the LSF, which increases the risk of
      undertreatment and residual disease, was more common than underestimation. The
      CIG minimized perceptual error and provided the best cryosurgical precision.

PMID- 8252147
TI  - Progesterone.

PMID- 8252148
TI  - Changes in women's physical health during the first postpartum year.
AB  - OBJECTIVE: To examine changes in women's physical health during the first
      postpartum year. DESIGN: Participants completed surveys at 1, 3, 6, 9, and 12
      months post partum. PARTICIPANTS AND SETTING: Four hundred thirty-six first-time
      mothers who gave birth at one of two St Paul, Minn, hospitals during a 12-month
      period and who met the criteria for the study. MAIN OUTCOME MEASURES: Physical
      symptoms and number of illness days experienced within the previous 2 weeks.
      RESULTS: Physical problems seen at a higher prevalence at 1 month post partum
      included breast symptoms, vaginal discomfort, fatigue, hemorrhoids, poor
      appetite, constipation, increased sweating, acne, hand numbness or tingling,
      dizziness, hot flashes, and illness days. Several of these disorders-
      hemorrhoids, dizziness, fatigue, and constipation--persisted beyond 1 month and
      were joined by other "late" problems, including respiratory symptoms, sexual
      concerns, and hair loss. Women who returned to the work force noted more symptoms
      of respiratory infections, and women with vaginal deliveries had a higher
      prevalence of hemorrhoids, vaginal discomfort, pain with intercourse, difficulty
      reaching orgasm, sinus problems, and acne. CONCLUSIONS: Recovery from childbirth
      often requires more than the 6 weeks traditionally allotted, and postpartum
      health appears to be affected by delivery type and work status.

PMID- 8252149
TI  - The clinical significance of ABO blood group incompatibility.
AB  - OBJECTIVE: To compare incidence, severity, and treatment of jaundice in ABO
      compatible and -incompatible infants. DESIGN: Retrospective chart review.
      SETTING: A 340-bed acute-care public and teaching hospital. PATIENTS OR OTHER
      PARTICIPANTS: All infants with blood groups A or B delivered in 1990 by Rh
      positive mothers with blood group O. On direct antiglobulin testing 65 infants
      had positive and 78 had negative results. The control group comprised 78 infants
      with blood group O born to mothers of blood group O. INTERVENTION: None. RESULTS:
      Infants who were ABO-incompatible and showed positive results to the direct
      antiglobulin test had the highest incidence of jaundice and underwent more tests
      and phototherapy. Infants who showed negative results to the direct antiglobulin
      test had jaundice incidence rates between those seen for control infants and
      infants who tested positive. Mean peak bilirubin levels did not differ
      significantly among the groups. CONCLUSION: Incompatibility of ABO blood group is
      associated with an increased incidence of jaundice and higher phototherapy rates.
      Clinicians should continue to be concerned about possible ABO incompatibility in
      infants with jaundice born to mothers with blood group O.

PMID- 8252150
TI  - The effectiveness of lumbar puncture in the evaluation of delirium and fever in
      the hospitalized elderly.
AB  - OBJECTIVE: To determine the value of the cerebrospinal fluid examination in the
      evaluation of hospitalized; elderly patients with delirium and fever. DESIGN: A
      retrospective case series of consecutive events during a 15-month period.
      SETTING: Tertiary care center. PARTICIPANTS: Elderly patients admitted to the
      University of Cincinnati (Ohio) Hospital between July 1, 1988, and October 1,
      1989, who had a lumbar puncture and cerebrospinal fluid evaluation to evaluate
      fever and mental status changes. MAIN OUTCOME MEASURES: Primary intracranial
      causes and the clinical characteristics of delirium and fever. RESULTS: Eighty
      one hospital admissions were reviewed. Fifty-seven (70%) of the lumbar punctures
      were performed as part of the admitting workup, and the remaining 24 (30%) were
      performed during the hospitalization. Eighty of the 81 cerebrospinal fluid
      cultures were negative for bacterial growth. The primary origins for fever and
      delirium included urinary tract infections (25%), pneumonia (22%), viral causes
      (17%), and metabolic causes/dehydration (14%). One case of bacterial meningitis
      was diagnosed in an alcoholic, 73-year-old man who was unresponsive in the
      emergency department. One case of presumed aseptic meningitis was diagnosed in a
      65-year-old man who presented with fever and headaches and a blood pressure of
      230/100 mm Hg. CONCLUSIONS: Most hospitalized, older patients with fever and
      delirium have primary causes of the confusion outside the central nervous system
      and may not require a routine evaluation of their cerebrospinal fluid.

PMID- 8252151
TI  - The impact of physician attitudes on patient satisfaction with care for low back
      pain.
AB  - We wished to determine whether patient satisfaction was related to physicians'
      confidence in their abilities to effectively manage low back pain, and to examine
      their attitudes about patients with back pain. The confidence and attitudes of
      primary care providers were determined using self-administered questionnaires.
      Patient satisfaction with care was assessed during telephone interviews conducted
      3 weeks after a clinic visit for low back pain. The study was conducted in a
      primary care clinic of a large health maintenance organization. Completed surveys
      were obtained from 21 primary care providers (18 physicians and three physician
      assistants) and 270 of their patients with low back pain. Three satisfaction
      scales specific to low back pain were used to measure patient satisfaction with
      regard to information received from provider, caring, and effectiveness of
      treatment. The results showed that the providers' attitudes about patients with
      low back pain were not associated with any of the patient satisfaction measures.
      However, patients of more confident providers were significantly more satisfied
      with the information they received than were patients of less confident
      providers. These differences could not be explained by years in practice, length
      of visit, patient demographics, or the severity and duration of low back pain.
      These findings suggest that providers who have more confidence in their abilities
      to effectively manage low back pain may in fact be more effective patient
      educators.

PMID- 8252152
TI  - A practical approach to treatment of the obese patient.
AB  - Obesity is one of the most common conditions encountered by primary care
      physicians, yet both physicians and patients are often frustrated by current
      approaches to its management. Recent advances in our understanding of obesity
      enable the physician to evaluate the contributions of biologic and environmental
      factors to the patient's obesity, to determine the degree of medical risk posed
      by the obesity, and to establish realistic goals for treatment. The chronic and
      relapsing nature of obesity requires ongoing support and vigilance. An
      individualized approach to obesity management, based on careful evaluation of
      biologic, psychologic, and social factors, can be successfully developed and
      implemented by the office-based primary care physician.

PMID- 8252153
TI  - Coffee. Facts and controversies.
AB  - In this article, we review current literature on coffee, both regular and
      decaffeinated, and its potential effects in humans. Moderate coffee consumption
      is believed to have no persistent effect on blood pressure. Large intake of
      coffee may increase total cholesterol levels; boiled coffee increases cholesterol
      levels more than filtered coffee. Consuming more than four cups per day may be
      associated with increased risk of acute myocardial infarction. There appears to
      be an association between urinary bladder cancer and coffee consumption. No
      association was found between ingestion of coffee and incidence of duodenal ulcer
      and ulcerative colitis. Increased coffee consumption by pregnant women appears to
      decrease fetal birth weight. Fetal heart rate, respiration, and both maternal and
      fetal anemia are increased with coffee consumption but coffee has not been shown
      to be teratogenic. Coffee consumption appears to pose no particular threat in
      most people if consumed in moderation. Naturally decaffeinated, filter-brewed
      coffee further diminishes its potential harmful effects.

PMID- 8252154
TI  - The health care of children and youths with disabilities. Council on Scientific
      Affairs, American Medical Association.
AB  - Nearly 2 million adolescents between ages 10 and 18 years have a chronic
      condition associated with limited activity. Reflecting the interaction between
      functional ability and socioeconomic influences, an adolescent living in poverty
      and those with parents with less than a ninth-grade education are almost twice as
      likely to be disabled as other adolescents. Most children with disabilities have
      a regular source of health care. These young people and their families, however,
      may face major financial problems and are often in need of protection from
      excessive out-of-pocket expenses. This issue becomes more prominent during late
      adolescence as youths leave the home setting, become financially independent,
      marry, or transfer from a pediatric to an adult health care system. Treating
      children and youths with disabilities necessitates cooperation among physicians,
      schools, community agencies, and families. Although not necessarily a problem for
      family physicians, an additional challenge for pediatricians is helping
      adolescents make the transition from the pediatric to the adult health care
      system. As the survival rate of children with disabilities increases,
      pediatricians are faced more frequently with having to prepare their adolescent
      patients and their families for transfer to adult care providers.

PMID- 8252155
TI  - Differential diagnosis in Cushing's syndrome: the role of inferior petrosal sinus
      sampling.

PMID- 8252156
TI  - On the relationship between regional circulation and systemic blood pressure.
AB  - OBJECTIVES: The relationship between regional circulation (blood flow or
      calculated resistance) and systemic blood pressure (BP) is only poorly documented
      in the range of intermediate to low BP. METHODS: In 75 subjects covering the BP
      range from low, over intermediate, to high BP, venous occlusion plethysmographic
      recordings were performed at the calf and finger vessels. Correlations were
      calculated between regional blood flow or vascular resistance and BP defined from
      office and from 24 h ambulatory BP registrations, at rest and during reactive
      hyperaemia. RESULTS: At any BP level, finger blood flow at rest and during
      reactive hyperemia was higher than calf blood flow, and resistance was lower. The
      interval of 90-100 mmHg office diastolic BP was characterized by significantly (p
      < 0.001) higher resting finger blood flow; the increase in resting muscle blood
      flow was less pronounced. At rest and during reactive hyperaemia there was a
      stepwise increase in calf regional vascular resistance in parallel with
      increasing BP. For the finger circulation, increased vascular resistance was only
      observed for the higher BP values. Correlations between calf and finger vascular
      resistances and BP were positive and highly significant over the whole BP range,
      both for office (0.650 < r < 0.776) and for ambulatory BP (0.531 < r < 0.781).
      These correlations remained significant after adjustment for the age dependency.
      Increases in calf and finger blood flow induced by arterial occlusion were
      highest for the lowest BP quintiles. CONCLUSIONS: Our data further indicated that
      the capacity to dilate decreased progressively with increasing BP level (from
      asymptomatic low to high BP) for both calf and finger circulation.

PMID- 8252157
TI  - Should vancomycin be used empirically in febrile patients with prolonged and
      profound neutropenia? Results of a randomized trial.
AB  - OBJECTIVES: We conducted a randomized trial with ceftazidine alone or associated
      with amikacin or vancomycin to investigate the efficacy of the daily 3 g dosage
      of ceftazidime and the efficacy of monotherapy with ceftazidime and to determine
      if vancomycin should be added empirically. METHODS: Patient inclusion criteria
      were: age over 10 years, therapeutically-induced neutropenia and fever for at
      least three hours above 38.5 degrees C in absence of a clear non-infectious
      aetiology. Patients were randomized into three groups: group C, ceftazidime alone
      3 g/day; group CA, ceftazidime 3 g/day plus amikacin 15 mg/kg/day; or group C,
      ceftazidime 3 g/day plus vancomycin 1.5 g/day. RESULTS: Results from one hundred
      and two episodes of fever were analyzed. The underlying diseases were
      haematological malignancies (89 patients) and solid tumours (13 patients). The
      median duration of neutropenia (< 0.5 x 10(9) PMN/L) was 18 days and the minimum
      duration of 7 days. The main criterion for the analysis of efficacy was the onset
      of a major infectious event, i.e. death related to documented or suspected
      infection and any infectious event considered life-threatening or hindering
      future treatment of the underlying disease. Eight (22%) patients in group C
      developed major infectious events compared with four (13%) in group CA and none
      in group CV (p < 0.01). Major infectious events were mainly due to Gram-positive
      organisms, particularly Streptococcus species. CONCLUSION: We conclude that: 1)
      ceftazidime alone and in association with amikacin is effective in preventing
      Gram-negative major infectious events; and 2) vancomycin should not be added only
      when a Gram-positive infection is documented, but used empirically.

PMID- 8252158
TI  - Acetylator polymorphism in Alzheimer's disease.
AB  - OBJECTIVES: To elucidate whether any relationship exists between genetic
      acetylator polymorphism and the risk of developing Alzheimer's disease. METHODS:
      Acetylator polymorphism has been determined, using sulphamethazine, in 54
      patients with Alzheimer's disease or senile dementia of Alzheimer type and in 93
      age-matched controls. RESULTS: Thirty-one patients (57.4%) and 54 controls (58%)
      were classified as slow acetylators (non-significant difference). No relation was
      found between acetylator polymorphism and age at onset of disease and scores of
      Minimental examination and Blessed, Tomlinson & Roth scale in the group of
      patients with Alzheimer's disease/senile dementia of Alzheimer type. CONCLUSIONS:
      Our results do not support the existence of any relationship between acetylator
      polymorphism and the risk of developing Alzheimer type dementia.

PMID- 8252159
TI  - Predictive value of synovial fluid analysis in rheumatoid arthritis. A 7.5-year
      follow-up study.
AB  - OBJECTIVES: To evaluate the prognostic value of some synovial fluid variables in
      patients with rheumatoid arthritis. METHODS: Twenty-nine patients with erosive
      rheumatoid arthritis and hydropsy in a knee joint were followed for 7.5 years in
      a prospective study. At the start of the study the knee joints were aspirated and
      15 synovial fluid variables were analyzed. The patients were divided into two
      groups according to whether or not there had been progress of radiologically
      detected destruction in the knee joints during the follow-up. RESULTS: Of the
      synovial fluid variables at the start, only C3 (p = 0.030) and acid phosphatase
      (p = 0.047) differed significantly between the groups, the former being lower and
      the latter higher in patients with deterioration of knee joints. CONCLUSIONS:
      These preliminary results may indicate that low synovial fluid C3 and high acid
      phosphatase predict poor prognosis in a joint affected by rheumatoid arthritis.

PMID- 8252160
TI  - Acquired von Willebrand's syndrome associated with decrease of plasminogen
      activator and its inhibitor during hypothyroidism.
AB  - OBJECTIVES: In a prospective study we searched for von Willebrand's syndrome
      during hypothyroidism and investigated the effects of treatment with thyroid
      hormones on plasma concentrations or activities of the factors involved in von
      Willebrand's disease in addition to tissue plasminogen activator and plasminogen
      activator inhibitor 1. METHODS: Eleven patients with hypothyroidism were tested.
      Factor VIII coagulant activity (VIIIc), von Willebrand factor (vWf:Ag), von
      Willebrand factor activity (vWf:RCo), tissue plasminogen activator antigen (tPA)
      and plasminogen activator inhibitor activity (PAI) was monitored before and after
      correction of hypothyroidism by hormone supplementation. RESULTS: Five patients
      had laboratory evidence of type I von Willebrand's disease. The other six
      patients had concentrations or activities of the factors involved in von
      Willebrand's disease within the normal range. In all cases except one, during
      thyroxin treatment, von Willebrand factors returned to normal if initially low,
      or increased clearly if initially normal. With the correction of hypothyroidism,
      an increase of tPA was noted in the eleven patients, associated with a
      significant increase of PAI. CONCLUSION: Laboratory evidence of von Willebrand's
      disease is common during hypothyroidism. Study of plasminogen activator and its
      inhibitor suggest a decrease of von Willebrand factor synthesis during
      hypothyroidism.

PMID- 8252161
TI  - The paradox of treating thyrotoxicosis with amiodarone.

PMID- 8252162
TI  - Immune-inflammatory response in the totally replaced hip: a review of
      biocompatibility aspects.

PMID- 8252163
TI  - Ethical aspects of the doctor-patient relationship.
AB  - Recently, the doctor-patient relationship has undergone major structural change
      by growing pressure from an ethic of personal autonomy, that gives patients
      greater control over their own lives, on a paternalistic "helpful healer's"
      ethic, whereby the doctor determines what should be done. It is a change in which
      informed consent by the patient has come to the fore in the traditional
      relationship with his doctor-as-friend-and-counsellor. The change is not without
      drawbacks as regards the quality of medical practice. The main characteristics of
      the two kinds of ethics are contrasted and some inferences drawn for the future
      course of medical practice.

PMID- 8252164
TI  - Recurrent abdominal pain due to hereditary angio-oedema.

PMID- 8252165
TI  - Bouveret's syndrome due to four large gall stones.

PMID- 8252166
TI  - Anticardiolipin antibodies associated with hypernephroma.

PMID- 8252167
TI  - Henoch-Schonlein purpura occurring in association with carcinoma of the breast.

PMID- 8252168
TI  - Pheochromocytoma-like catecholamine levels induced by clonidine cessation.

PMID- 8252169
TI  - Carpian tunnel syndrome: a most unusual presentation of leishmaniasis.

PMID- 8252170
TI  - Efficacy and safety of flexible fibreoptic bronchoscopy in the elderly.

PMID- 8252171
TI  - Hepatitis C virus transmission.

PMID- 8252172
TI  - Triple-blindness.

PMID- 8252173
TI  - Renal adenocarcinoma and exposure to asbestos.

PMID- 8252174
TI  - The use of ELISA with antigen 60 in a serological study of human tuberculosis.

PMID- 8252175
TI  - Treatment of membranous nephropathy.

PMID- 8252176
TI  - Synovial fluid analysis. The forgotten investigation.

PMID- 8252177
TI  - Amyotrophic lateral sclerosis an enigmatic disease with B-cellular and anti
      retroviral immune responses.
AB  - OBJECTIVES: The most frequent sporadic adult motor neuron disease, amyotrophic
      lateral sclerosis, affects more men, follows no epidemiologic pattern, and was
      long considered a pure spinal cord disorder. It now becomes evident that the
      disease is characterized by spinal, cerebral and extra-neuromuscular changes
      including B-cellular responses and ultrastructural skin alterations. Do these
      parameters identify subgroups or correlate with the male preponderance of the
      disease? METHODS: We analyzed age at and site of onset, sex, duration of clinical
      disease, and human foamy retroviral seroreactivity in 47 consecutive patients
      with a definite diagnosis of amyotrophic lateral sclerosis. The results were
      compared with antivisna seroreactivity, immunoglobulin isotypes, circulating
      immune complexes, neopterin and beta 2-microglobulin as well as skin biopsies in
      respective subsets of the same 47 patients. RESULTS: Seroreactivity to
      recombinant human spuma retrovirus (HSRV) envelope and/or capsid protein was
      positive in 20/47 amyotrophic lateral sclerosis patients, and 28/30 competed with
      specific retroviral antibodies on maedi-visna antigen. Anti HSRV-seronegative
      patients had lower immunoglobulin IgG3 isotype concentrations, while HSRV-gag
      plus HSRV-env antibody positives demonstrated highest circulating IgG immune
      complexes. All 11 amyotrophic lateral sclerosis patients partially reacting to
      recombinant HSRV-env or HSRV-gag antigen were men, and male amyotrophic lateral
      sclerosis patients tended to have higher total cerebrospinal fluid protein
      levels. Neopterin and beta 2-microglobulin as markers of a cellular immune
      activation remained basically normal in serum and cerebrospinal fluid.
      CONCLUSION: We suggest a particular B-lymphocytic and retroviral involvement in
      this enigmatic, relentlessly progressing, at present untreatable and most
      frequent neurological system degeneration. To our opinion this situation
      justifies the search for novel anti-retroviral therapeutic strategies.

PMID- 8252178
TI  - Increased plasma angiotensinogen in cardiac transplantation patients.
AB  - OBJECTIVES: Interleukin 6 (IL-6) stimulates the production of angiotensinogen
      (renin substrate, RS), an acute phase reactant and the precursor of the potent
      vasoconstrictor angiotensin II. This study assesses the effect of cardiac
      transplantation on plasma levels of angiotensinogen and interleukin 6. METHODS:
      Effects of cardiac transplantation on plasma levels of renin substrate and IL-6
      were studied in twelve patients with NYHA IV end-stage heart failure. Renin
      substrate, IL-6, plasma renin activity, C-reactive protein and serum amyloid A
      were determined 1 day before cardiac transplantation, and 1 day, 1 week, 4 weeks
      and 12 weeks postoperatively. Renin substrate was measured by both direct and
      indirect radioimmunoassay. An indirect assay measures intact renin substrate
      only, capable of releasing angiotensin I, while a direct assay measures both
      intact renin substrate and des-angiotensin I-renin substrate, the residue of
      renin substrate after cleavage of angiotensin I. RESULTS: Plasma renin substrate
      and IL-6 increased significantly on day 1 as compared with preoperative levels.
      Plasma renin substrate increased (measured by direct and indirect assay) by 64
      and 50%, respectively, IL-6 levels by 43%. Plasma IL-6 returned to preoperative
      (normal) levels by 4-12 weeks. Plasma renin substrate levels remained elevated
      for the follow-up period of 12 weeks. The direct assay always gave higher values
      than the indirect assay, presumably due to consumption of renin substrate by
      renin. Consequently, a negative correlation between plasma renin activity and
      renin substrate measured with indirect assay was observed. CONCLUSIONS: Our
      findings suggest that cardiac transplantation brings about an acute phase
      reaction, mediated partly by IL-6, with increased synthesis of acute phase
      proteins like renin substrate. This may result in increased angiotensin II
      levels. Considering the trophic effects of angiotensin II on vascular tissue,
      increased production of renin substrate may contribute to the development of
      proliferative cardiovascular changes in heart transplant recipients.

PMID- 8252179
TI  - Kaposi's sarcoma in organ transplant recipients. The Collaborative
      Transplantation Research Group of Ile de France.
AB  - OBJECTIVES: Kaposi's Sarcoma (KS) is a tumour of multicentric origin with
      increased frequency after organ transplantation. To date, only North American
      data from the Cincinnati Transplant Tumor Registry have given some information
      about this disease in organ transplant recipients, but its true prevalence still
      has to be determined. In order to analyze Kaposi's sarcoma after kidney, liver
      and heart transplantation, we performed a retrospective study using the oldest
      registry of organ transplant recipients in Europe. METHODS: Among all 7923 organ
      transplant recipients recorded in the Groupe Collaboratif de Recherche en
      Transplantation de l'Ile de France (GCIF) registry from 1968 to 1990, we analyzed
      the prevalence and the clinical characteristics of Kaposi's sarcoma in 6229
      kidney, 727 liver and 967 heart transplant recipients. In the subgroup of kidney
      transplant recipients, we assessed the role of cyclosporine on disease evolution.
      RESULTS: Overall prevalence of Kaposi's sarcoma after organ transplantation was
      0.52%, but it was significantly higher among liver (1.24%) than among kidney
      (0.45%) and heart (0.41%) transplant recipients. Chronic hepatitis B surface
      antigen carriers were more frequent in liver than in kidney transplant recipients
      who developed Kaposi's sarcoma (66% vs 21%, p < 0.03). Following kidney
      transplantation, Kaposi's sarcoma was more severe in patients receiving
      cyclosporine (n = 16) when compared with those under conventional
      immunosuppression (n = 12). CONCLUSION: True prevalence of Kaposi's sarcoma among
      European transplant recipients is high (0.52%) and appeared significantly higher
      in liver compared with other organ transplant recipients. Cyclosporine seems to
      increase severity of the disease among kidney transplant recipient.

PMID- 8252180
TI  - Therapy of active chronic hepatitis with recombinant alpha 2b-interferon: an 18
      month follow-up.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of interferon
      therapy in patients with "active" chronic hepatitis. METHODS: A total of 115
      patients with histological diagnosis of active chronic hepatitis were enrolled in
      the study and treated with recombinant alpha 2b-interferon at a dosage of 3 MU, 3
      times a week, for a 6 month period. Patients who showed a complete normalization
      of serum aminotransferase levels were followed for further 12 months, in which no
      treatment was performed. RESULTS: After 6 months of treatment, 50 (43.4%)
      patients showed normalized serum aminotransferase levels and among these
      "responders", 18 (36%) showed a persistent normalization 12 months after stopping
      interferon therapy. Only 7 patients at the end of the study agreed to a second
      liver biopsy which showed a decrease in Knodell's index and a clear-cut reduction
      of inflammation and lobular necrosis. CONCLUSION: Interferon is useful for the
      treatment of chronic active anti-HCV positive hepatitis but the beneficial
      responses are often transient. Future therapeutic strategies and the development
      of direct assay for HCV in serum and liver are necessary to understand the real
      role of interferon in chronic anti-HCV positive hepatitis.

PMID- 8252181
TI  - Oesophageal versus angina chest pain: a diagnostic challenge.

PMID- 8252182
TI  - Database consultation for phase I studies in Europe.

PMID- 8252183
TI  - The hungry bone syndrome: clinical problems and therapeutic approaches following
      parathyroidectomy.

PMID- 8252184
TI  - Gemella haemolysans endocarditis with colonic carcinoma.

PMID- 8252185
TI  - Leiomyosarcoma of Meckel's diverticulum in the proximal jejunum.

PMID- 8252186
TI  - Jaccoud's arthropathy in primary Sjogren's syndrome with benign
      hypergammaglobulinaemic purpura.

PMID- 8252187
TI  - Diet and blood lipids in vegetarians in Israel.

PMID- 8252188
TI  - Lymphangioleiomyomatosis: unsuccessful treatment with luteinizing-hormone
      releasing hormone analogues.

PMID- 8252189
TI  - Wegener's granulomatosis presenting as pseudo tumoural disease.

PMID- 8252190
TI  - Retroviral gene transduction of circulating progenitor cells in patients with
      metastatic breast cancer.
AB  - The use of somatic gene therapy for the treatment of breast cancer has many
      potential applications. Because chemotherapeutic protocols for breast cancer are
      commonly limited by bone marrow toxicity, transduction of genes into pleuripotent
      stem cells may allow the generation and maintenance of immune responses in the
      presence of lymphocytotoxic agents. The practical utility of stem cell isolation
      and transduction would be enhanced if stem cells circulating in the peripheral
      blood could be isolated in patients, however this approach has been limited by
      the small numbers of such cells in the circulation. In these studies, recombinant
      granulocyte colony stimulating factor (G-CSF) was administered to patients with
      metastatic breast cancer to increase the number of circulating stem cells. Stem
      cells in the peripheral blood were then isolated and a retroviral vector (LXSN)
      was used to transduce the neomycin phosphotransferase gene into these cells. Gene
      transduction was demonstrated by resistance to the toxic effects of a neomycin
      analog (G418) and the detection of retroviral DNA from transduced cells. A
      practical method of transfer of exogenous genes into the circulating pleuripotent
      stem cells of patients with metastatic breast cancer is documented by these
      experiments. Application of these findings may allow the generation of cells
      resistant to anti-neoplastic agents or unique lymphoid effector cells with potent
      immune functions for the treatment of patients with metastatic breast cancer.

PMID- 8252191
TI  - Targetted phototherapy with sensitizer-monoclonal antibody conjugate and light.
AB  - Photodynamic therapy (PDT) was performed in vitro and in vivo using monoclonal
      antibody conjugated to hematoporphyrin (HP). The antibody (45-2D9) recognized a
      cell surface glycoprotein on cells derived from NIH 3T3 cells which were
      transformed with the ras oncogene (45-342). Radionuclide imaging with either
      In111 or I125 chelated to 45-2D9 or the isotype identical (IgG1) antibody MOPPC
      21 revealed selectivity of 45-2D9 for 45-342 flank tumours in nude mice, and
      minimal targetting for a 45-342 clone which did not express the cell surface
      glycoprotein. The 45-2D9-HP conjugate resulted in selective killing of the 45-342
      line compared with the parent line in vitro. At HP concentrations of 76
      micrograms ml-1, the 45-2D9-HP conjugate resulted in significantly more long-term
      cures of PDT treated flank tumours compared with free HP at the same
      concentration. 45-2D9 alone had no effect on tumour growth. The antibody-HP
      conjugate resulted in significantly less local toxicity compared with standard
      Photofrin II PDT, and also achieved a greater number of long-term cures. This
      'photoimmunotherapy' demonstrates the ability to treat established tumours with
      greater efficacy and decreased morbidity, probably due to specific sensitizer
      targetting which allows normal surrounding tissue to be spared upon illumination.

PMID- 8252192
TI  - Hepatopancreatic uptake and elimination of 5-fluorouracil after intravenous
      injection.
AB  - The efficacy of 5-fluorouracil (5FU) chemotherapy depends, in part, upon
      maintaining adequate intracellular levels of active metabolites. The uptake,
      distribution and elimination of 5FU and 5FU-anabolites were determined after an
      intravenous bolus infusion of 5FU, 15 mg kg-1, and the relationship between serum
      and tissue levels were evaluated. In six dogs samples of liver, pancreas, rectus
      abdominus muscle, blood, bile and pancreatic juice were collected at 0, 15, 45,
      90 and 120 min. Bile and pancreatic juice levels of 5FU followed the same pattern
      as the serum, rising rapidly and falling exponentially, suggesting elimination by
      simple diffusion. Elimination of anabolites was more complex. Tissue levels of
      anabolites were highest in the liver and peaked later than in the pancreas and
      muscle. They were unrelated to serum levels of 5FU. The higher and more sustained
      levels of 5FU-anabolites in the liver may be responsible for some of the
      beneficial effects of 5FU chemotherapy on hepatic tumours.

PMID- 8252193
TI  - Clinical and biological prediction of axillary and internal mammary lymph node
      metastases in breast cancer.
AB  - We assessed the relationships among histological axillary (AX) or internal
      mammary (IM) metastases and clinical and biological variables, and then attempted
      to evaluate their predictive values for AX and IM metastases in 128 patients with
      invasive breast cancer. As the results, these clinical and biological variables
      were significantly correlated with AX and IM metastases. However, a metastatic
      index calculated from clinical and biological variables was not much better in
      prediction of the AX metastases than axillary nodal status, whereas it was useful
      to predict the IM metastases. Thus, the predictive ability was still limited.
      Since accurate prediction of AX and IM metastases is critical to therapeutic
      choice, however, further study would be required.

PMID- 8252194
TI  - The anatomy of missed breast cancers.
AB  - Missed breast cancer continues to account for the highest percentage of medical
      malpractice cases in the United States. A retrospective, computer-aided study was
      performed to investigate the mechanisms of missed breast carcinomas, missed
      either by mammography or by clinical exam. In a consecutive series of 509 breast
      cancers found in patients registered at a University Comprehensive Breast Cancer
      Clinic, no tumour that was 5 mm or less in maximal diameter was clinically
      palpable. This subgroup consisted of seven in situ and 32 invasive carcinomas.
      The incidence of palpable tumours in 5 mm increments increased so that when a
      tumour was between 11 and 15 mm in size, 48% of the lesions were palpable, and
      with tumours greater than 20 mm in size, 84% were palpable. There was a good
      correlation between size of the tumour as judged by mammography and the eventual
      size determined by histologic examination. Smaller breast cancers were detected
      by mammography than by physical examination. In a separate analysis of 553
      consecutive cases of breast cancer examined by mammography, there were 50 (9%)
      cases in which the cancer was not read from the mammogram. In retrospect, 10 of
      these mammograms were abnormal for a misinterpretation rate of 1.8%. Cancers
      associated with false negative mammograms occurred more often in younger women
      and in dense breast parenchyma than cancers detected by mammography. Cancers
      missed by mammography were smaller than palpable cancers detected by mammography,
      more often had negative nodes and presented with a lower stage of disease. Breast
      augmentation implants were associated more frequently with missed breast cancers,
      with 5/8 clinically detected breast carcinomas being undetected by mammography.
      An asymmetric mass was more often associated with cancers missed by mammography,
      accounting for the sole sign of malignancy in 3% of all cancers, but was the
      source of 14% of false negative exams. Architectural distortion, ill-defined or
      well circumscribed masses or calcifications as mammographic signs of malignancy
      were not associated with an increased frequency of missed cancers. Three
      'interval' breast cancers occurred in this series and are included in the false
      negative mammograms. It is concluded that the threshold of clinically detected
      breast cancers is 6 mm and experienced clinicians do not detect the majority of
      breast cancers until the lesions are greater than 16 mm. Mammography has a
      defined misinterpretation and false negative rate. Likewise, asymmetric
      mammographic densities that are greater than 16 mm and are not palpable may be
      followed, since most breast cancers are palpable in this range.

PMID- 8252195
TI  - 13C- and 31P-NMR studies of human colon cancer in-vitro and in-vivo.
AB  - We report comparative 31P-NMR studies in-vivo and in-vitro of the human
      adenocarcinoma cell line HCT-116 in a high-density, perfused microcarrier culture
      and as a tumour from the same cell line grown in three different immune
      suppressed animal models (NIH triple deficient, Nude, SCID). The phosphate
      metabolite ratios, pHNMR and intracellular free magnesium, derived from the 31P
      NMR spectra, were compared for the in-vivo and in-vitro systems. Results obtained
      with HCT-116 cells on microcarrier beads are quantitatively similar to that of
      small (122 mm3), tumours in-vivo derived from the same cell line in any of the
      immune-suppressed animal systems studied. This suggests that in-vitro
      microcarrier cell culture serves as a useful model system for deriving
      information about metabolism of small, tumours in-vivo. It offers the additional
      advantages of allowing for precise control of substrate milieu, perfusion and
      oxygenation. The microcarrier system was also used to measure flux through
      glycolysis and the pentose cycle. In particular, we measured glucose utilization
      and the production of lactate, alanine, glutamine and glycogen in proton
      decoupled 13C-NMR experiments following administration of [1-13C]glucose. We
      found that (63% +/- 6%) of the glucose utilized was released as [3-13C] lactate
      in the presence of oxygen, indicating that the HCT-116 cells have a high level of
      aerobic glycolysis. Serial labelling experiments with [1-13C] glucose and [6-13C]
      glucose reveal that at least (11.6% +/- 1.3%) of the glucose utilized enters the
      pentose cycle. We determined that (6.9% +/- 1.2%) of the glucose utilized is
      recycled to glucose via the pentose cycle while (4.7% +/- 1.4%) of the glucose
      utilized enters the pentose cycle to form lactate. The high rate of recycling via
      the pentose cycle suggests that a significant fraction of cellular NADPH is
      generated by the pentose cycle as opposed to generation by the malate-pyruvate
      shuttle.

PMID- 8252196
TI  - Testicular cytotoxicity of intravenous procarbazine in rats.
AB  - Although the testicular cytotoxicity of procarbazine has been evaluated in the
      rat, previous models have utilized routes other than the intravenous one, and
      have generally employed multiple-dose regimens. In this report, we describe
      testicular toxicity in the Sprague-Dawley rat following a single intravenous
      bolus of procarbazine (0-700 mg kg body weight), with necropsy 59 +/- 2 days
      later. Testicular toxicity was evaluated qualitatively by histology and
      quantitatively by testicular weight, sperm head count, repopulation index and
      epididymal index. Effects of procarbazine on heart, lung, liver and kidney
      histology were evaluated qualitatively. Progressive dose-dependent testicular
      atrophy and oligospermia occurred at low and intermediate dosages of
      procarbazine. Marked testicular atrophy, oligospermia and germinal hypoplasia
      were observed at high dosages (500 and 700 mg kg-1 body weight). LD50 at day 59
      for procarbazine appears to be approximately 600 mg kg-1 body weight using this
      regimen. This model will facilitate the study of techniques to avoid drug-induced
      testicular damage.

PMID- 8252197
TI  - Localization of insulinoma by laparoscopic infragastric inspection of the
      pancreas and contact ultrasonography.
AB  - A new technique for localizing pancreatic insulinoma is described. This consists
      of a laparoscopic examination of the body and tail of the pancreas through an
      infragastric approach combined with contact ultrasonography of the gland.
      Accurate localization of an occult insulinoma in the body of the pancreas was
      achieved in one patient with the technique described. Laparoscopic contact
      ultrasonography of the pancreas by the infragastric approach should be as
      reliable as open intraoperative ultrasonography and constitutes the first step in
      the laparoscopic treatment of insulinoma.

PMID- 8252198
TI  - Regional lymphatic drug exposure following intraperitoneal administration of 5
      fluorouracil, carboplatin, and etoposide.
AB  - Intraperitoneal (i.p.) administration of chemoterapeutic agents results in
      greater total drug exposures in the peritoneal cavity than in plasma. A study on
      the drug exposure for i.p. lymphatics of pigs, receiving 5-fluorouracil (5-FU),
      etoposide (VP-16) and carboplatin (CBDCA) by the i.p. route was conducted. Drug
      concentrations in peritoneal fluid, plasma, and thoracic duct lymph were
      monitored over the ensuing 3 h. 5-FU appeared rapidly in thoracic duct, lymph and
      plasma. The lymph concentration declined after 20 min while the plasma
      concentration remained stable. CBDCA reached a stable concentration in lymph and
      plasma after 60 min. VP-16 peaked in the lymph after 20 min, whereas the plasma
      concentration continued to rise for 150 min; the peritoneal half-life for VP-16
      was too long for clearance to be defined. Total drug exposure (AUC) was for 5-FU
      5.7-fold greater for lymph than for plasma and for CBDCA equal in both
      compartments. VP-16 had a 2.1-fold higher AUC for lymph than for plasma. The
      results indicate that the i.p. route of administration results in a greater
      exposure of the lower thoracic duct lymph than the plasma to 5-FU, produces only
      a marginally increased exposure to VP-16, and results in no difference for CBDCA.
      The efficacy of 5-FU is a function of total drug exposure. The results reported
      provide a strong rationale for evaluating the adjuvant use of i.p. 5-FU in
      colorectal and gastric carcinoma.

PMID- 8252199
TI  - Hepatic intra-arterial lipiodol ultrasound guided biopsy in the management of
      hepatocellular carcinoma.
AB  - One hundred and fifty-one consecutive new patients with suspected hepatocellular
      carcinoma (HCC) were investigated from 1989 to 1990. Ultrasound showed the
      tumours to be inoperable in 111 patients. Selective hepatic angiography revealed
      17 more patients with inoperable HCC. Hepatic intra-arterial lipiodol (HIAL) was
      injected in the remaining 23 patients. In 16 of them, a clinical decision could
      be reached basing on the radiological findings. Hepatic intra-arterial lipiodol
      ultrasound (HIAL/USG) guided biopsy was done in seven patients with suspicious
      lesions. Histology obtained with this method revealed hyperplastic cirrhotic
      nodules in four patients (two with suspected HCC and two with suspected
      secondaries). In another two patients, the suspected lesions were confirmed to be
      malignant. In the last patient who had received chemotherapy for extensive HCC,
      HIAL/USG guided biopsy revealed necrotic tissue only. At laparotomy, diffuse
      infiltrative abnormality was found and repeated biopsy confirmed residual
      malignancy in the necrotic tumour. We conclude that when there is radiological
      uncertainty as to the nature and extent of the HCC, HIAL/USG guided biopsy can
      help the clinician to make important decisions.

PMID- 8252200
TI  - Co-stimulation with IL-2, but not via CD28, overcomes immunosuppression by breast
      tumour-derived factors on the in vitro stimulation of human T-cells.
AB  - In order to investigate the mode of action of tumour-derived immunosuppressive
      factor from breast cancer (TDS) we examined its function on human T-cells
      stimulated via CD3 and co-stimulated via CD28 or the IL-2 receptor. When added at
      the initiation of culture, TDS inhibited anti-CD3 stimulation and co-stimulation
      by anti-CD28. In contrast, co-stimulation with IL-2 greatly diminished the TDS
      inhibition of anti-CD3 stimulated cells. Activation by IL-2 alone was also
      inhibited at the initiation of culture. When PBMC were activated with IL-2 or
      anti-CD3 for three days and then exposed to TDS for a further 3 days, only the
      proliferation of the cells pre-activated with IL-2 was inhibited; the cells pre
      activated via CD3 were refractory to TDS inhibition. Pre-activation with anti-CD3
      for 48 h was required for this to develop. The cytotoxicity of cells pre
      activated with anti-CD3 was lower than that of cells exposed to IL-2, but killing
      obtained from cultures pre-activated with anti-CD3 plus IL-2 was equivalent to
      that obtained with IL-2 alone and additionally, these pre-activated cells were
      not subject to inhibition upon subsequent exposure to TDS.

PMID- 8252201
TI  - Tumours of heterotopic salivary tissue in the upper cervical region in children.
AB  - Heterotopic salivary tumours in the upper neck are rare. Three children, one with
      mucoepidermoid carcinoma and two with pleomorphic adenoma in ectopic cervical
      sites are presented. Local complete excision was successful in the patients with
      pleomorphic adenoma. More extensive surgery was undertaken for the mucoepidermoid
      carcinoma. All three patients remain disease free at 3-6 years follow-up.
      Oncogenesis of heterotopic salivary tissue entrapped in an upper cervical lymph
      node during embryogenesis is a possible etiological mechanism. In a patient with
      a cervical malignant salivary tumour, a careful search should be made to find a
      primary tumour. In the event of a negative search, this should be considered the
      primary tumour and treated appropriately.

PMID- 8252202
TI  - Superselective intra-arterial chemotherapy with mitomycin C for hepatocellular
      carcinoma.
AB  - Thirty-six patients with primary hepatocellular carcinoma were treated by
      superselective intra-arterial chemotherapy with mitomycin C (SIAC) between 1981
      and 1990, either as primary chemotherapy without operation (28) or as additional
      therapy after resective surgery (8). During the same period 10 patients were
      resected radically and 26 patients treated conservatively. The overall response
      rate to SIAC was 25% (9/36), comprising two complete and seven partial responses.
      The cumulative 5-year survival rate was significantly related to the percentage
      of hepatic replacement (PHR) (P < 0.01) and to resective surgery (P < 0.01).
      Overall 5-year survival was only 4% and all the patients with PHR over 75% died
      within 2 or 3 years. Cessation of chemotherapy was necessary in 72% of cases
      (26/36), because of tumour progression in 20 cases, chemotherapy toxicity in four
      and one technical error in one and patient refusal in one. The results of the use
      of SIAC as a chemotherapeutic agent for hepatocellular cancer may be regarded as
      disappointing, as the response rate remained low and the medication was unable to
      prevent tumour progression in most cases. We intend to use SIAC only for stage I
      II tumours and as additional therapy after surgery when the radicality remains
      uncertain.

PMID- 8252203
TI  - Gamma-probe guided localization of lymph nodes.
AB  - The initial draining lymph node (Sentinel node) of a tumour may reflect the
      status of the tumours spread to the remaining lymphatic bed. The sentinel node,
      which has been reported to predict metastatic melanoma, has recently been
      localized by a new invasive technique [1]. The goal of our pre-clinical trial was
      to test a non-invasive technique to localize the sentinel node. Gamma-probe
      guided localization was used to identify and then surgically remove the first
      draining lymph node(s) in 16 inguinal lymphatic basins of eight cats. This method
      was found to be comparable to an invasive method using a blue dye. Gamma-probe
      localization has several potential advantages in that it can: (a) precisely
      locate on the surface of the skin the position of an underlying lymph node, (b)
      intraoperatively guide the surgeon to the lymph node during dissection, (c)
      verify that the correct node has been biopsied, (d) determine the possible
      presence of residual lymph nodes, (e) allow lymph nodes to be harvested through a
      small incision as opposed to raising a skin flap, and (f) be rapidly and easily
      performed.

PMID- 8252204
TI  - Fine needle aspiration biopsy of palpable breast lesions. Review and statistical
      analysis of 1875 cases.
AB  - Fine needle aspiration biopsy (FNAB) is an increasingly accepted method for
      investigating palpable breast nodules. We reviewed our experience with a
      consecutive series of 1875 FNABs performed using 21 or 23 gauge butterfly
      needles. Correlation was made with histology (524 cases) or clinical follow-up (2
      70 months). Cytological diagnoses utilized histopathological terminology and were
      categorized as: unsatisfactory (93 or 4.96%); no evidence of malignancy (1295 or
      69.07%); atypical (183 or 9.76%); suspicious (42 or 2.24%); malignant (262 or
      13.97%). Of the 1571 benign aspirates, 220 or 14% were followed by excisional
      biopsy because of clinical suspicion, atypia or hypocellularity. Of these
      aspirates, 198 were benign while 22 proved to be malignant (one in situ ductal,
      one intracystic papillary, two tubular, one cribriform, seven ductal nos, three
      in situ and five infiltrating lobular carcinomas, two large cell lymphomas).
      Malignancy was detected histologically in 12.9% of unsatisfactory, 3.06% of
      benign but often hypocellular, 8.16% of atypical, 97.62% of suspicious and 100%
      of malignant aspirates. Considering only histologically verified breast aspirates
      and including suspicious cytodiagnoses, FNAB had a sensitivity of 93.23%, a
      specificity of 99.50%, positive and negative predictive values of 99.62% and 90%,
      and an overall diagnostic accuracy of 95.61%. This series clearly shows that FNAB
      effectively evaluates palpable breast lesions when careful consideration is given
      to clinical judgement, specimen procurement, diagnostic criteria and a clinically
      relevant reporting style.

PMID- 8252205
TI  - Epidermal growth factor receptor expression in squamous cell carcinoma of the
      hypopharynx.
AB  - Expression of the epidermal growth factor receptor (EGFR) has been demonstrated
      in normal and malignant squamous epithelia. Its presence has been suggested to be
      important in the pathophysiology and prognosis of epithelial cancers. Archival
      tumour specimens from 57 patients with squamous cell carcinoma of the hypopharynx
      were studied using OM-11-951, a new murine anti-EGFR monoclonal antibody which
      recognizes the receptor on deparaffinized tissue. By visual inspection, 28 (49%)
      tumours were EGFR negative; 29 (51%) tumours were EGFR positive. While patients
      whose tumours were EGFR positive were younger, there was no significant
      correlation with other clinical or pathological variables (including grade and
      stage). Patients whose tumours were EGFR negative had a median survival of 21
      (95% CI 4.3-37.7) months compared with a median survival of 17 (95% CI 11.4-22)
      months for patients whose tumours were EGFR positive. The difference was not
      statistically significant. A multiple regression analysis did not demonstrate
      EGFR status to be important in predicting survival. These data cast doubt on the
      prognostic significance of EGFR expression in this neoplasm.

PMID- 8252206
TI  - Bombesin stimulates growth of colon cancer in mice and decreases their survival.
AB  - Bombesin (BBS) stimulates cellular proliferation of both normal and transformed
      cells. The mouse colon cancer cells (MC-26) possess specific binding sites for
      BBS. The purpose of this study, therefore, was to examine the effect of chronic
      administration of BBS on in vivo growth of MC-26 tumours in Balb/c mice and on
      survival of tumour-bearing mice. Three groups of mice (n = 10 each) inoculated
      with MC-26 cells received either saline containing 0.1% bovine serum albumin
      (BSA), or BBS (5 micrograms kg-1 or 20 micrograms kg-1) dissolved with 0.1% BSA
      saline by intraperitoneal route three times a day for 15 days. BBS increased
      weight, DNA and RNA contents of MC-26 tumours. To examine the effect of BBS on
      survival rates of mice with MC-26 tumours, three groups of mice (n = 20 each)
      were treated for 31 days, as above. One group of mice inoculated with MC-26 cells
      received 0.1% BSA saline; the other group of MC-26-inoculated mice and the
      control group without tumour received BBS (5 micrograms kg-1) dissolved with 0.1%
      BSA saline. BBS significantly decreased the survival rate of mice bearing MC-26
      tumours (median survival; saline group: 42.5 days, BBS group: 32.0 days, P =
      0.037). None of the mice in the control group died during the experiment. BBS may
      stimulate in vivo growth of MC-26 cells through specific receptors.

PMID- 8252207
TI  - Patterns of occurrence of second primary non-mammary malignancies in breast
      cancer patients: results from 1382 consecutive autopsies.
AB  - An autopsy series on the patterns of occurrence of second primary non-mammary
      malignancies (SPNM) in breast cancer patients is presented. SPNM occurred in
      11.4% of breast cancer patients at a mean interval of 83.9 months. Seventy-five
      per cent of them occurred by the first decade following breast cancer. The most
      common system of SPNM occurrence was the female genital system, followed by the
      gastrointestinal system. The single organs most commonly involved were the colon
      and rectum, ovary and uterine cervix. There was no evident association between
      administration of radiotherapy or chemotherapy for the breast cancer and the risk
      for SPNM development except in the case of post-radiation sarcomas at or near the
      site of post-mastectomy radiotherapy. Death was caused by the breast cancer in
      28.7% of patients and by the SPNM in 53.5%. In 10.6% of the cases the SPNM was
      clinically interpreted as metastatic breast cancer until autopsy.

PMID- 8252208
TI  - Photodynamic therapy of squamous cell carcinoma. An evaluation of a new
      photosensitizing agent, benzoporphyrin derivative and new photoimmunoconjugate.
AB  - Photodynamic therapy for cancer depends on the relatively selective distribution
      of photosensitizing agents to malignant as compared with normal tissues,
      rendering the malignant cells more susceptible to light-mediated damage.
      Photodynamic therapy has been used with only moderate success to date. The
      purpose of this study was to compare a new photosensitizing agent, benzoporphyrin
      derivative (BPD), to the standard agent presently in use, photofrin II, in a
      hamster cheek pouch model of squamous cell carcinoma. As well we have
      investigated the potential of using a tumour-specific monoclonal antibody-BPD
      conjugate to improve the tumour localizing properties of BPD. Treatment consisted
      of photodynamic therapy with either photofrin II, BPD, or a tumour-specific anti
      epidermal growth factor receptor-BPD conjugate. Control groups of light alone,
      anti-EGFr, tumour non-specific MoAb, and tumour non-specific MoAb-BPD conjugate
      were included with the contralateral cheek pouch of each animal acting as a dark
      control. An assessment of differential delivery of BPD to tumour and to normal
      mucosa was undertaken using a spectrophotometric assay. Parametric statistical
      analysis included Student's t-tests and linear regression while non-parametric
      analysis was undertaken using Fisher's exact test. Animals receiving BPD alone
      demonstrated tumour-to-tissue levels of approximately 2:1 while animals receiving
      the tumour-specific anti-EGFr-BPD conjugate had significantly better
      tumour:tissue ratios of 26:1 (P < 0.005). Animals treated with photofrin II had a
      1 month cancer-free survival of 27% while animals treated with BPD had an
      improved survival of 67% (P = 0.03). The group treated with the tumour-specific
      anti-EGFr-BPD conjugate at a twentieth the total dose of BPD had an 80% 1 month
      cancer-free survival which was not statistically different from the group treated
      with BPD alone. Benzoporphyrin appears to be a more effective photosensitizing
      agent than Photofrin II and its tumour selectivity can be improved using a tumour
      specific monoclonal antibody conjugate.

PMID- 8252209
TI  - High-energy shock waves pyrotherapy. A new concept in extracorporeal tumour
      therapy.
AB  - High-intensity shock waves (HISW) waves can produce rapid and intense tissue
      heating. We have studied a novel device capable of simultaneous shock wave
      generation, focusing and extracorporeal delivery along with imaging of the
      proposed target. Shock waves are generated by piezo-electric crystals and target
      a focal point of 10 x 2 mm. In a preliminary study, three groups of land race
      pigs received HISW to discrete points on the liver parenchyma. There was no
      mortality in any group. Cardiovascular monitoring revealed that HISW did not
      induce any haemodynamic changes during treatment and that core temperatures and
      liver function tests were unaffected by this therapy. Ultrasound monitoring
      during treatment demonstrated discreet hyperechoic areas with acoustic shadowing
      suggesting cavitation. Animals killed immediately after 48 h of HISW therapy had
      discrete necrotic cylinders within the liver with a mean diameter of 2 cm (+0.21
      SD). Histological examination revealed a pattern of necrosis and vascular changes
      suggestive of ischaemia. In addition, there were areas of coagulative necrosis
      consistent with thermal injury. Animals killed at 2 months had necrotic cavities
      which had become surrounded by mature fibrosis. These early results indicate that
      high energy shock waves delivered extracorporeally can cause specific destruction
      of liver tissue by focused hyperthermia and cavitation. Clinical studies of this
      device are required to assess the possible virtue of HISW in the treatment of
      liver and other tumours.

PMID- 8252210
TI  - Na(+)-dependent glutamine transport in the liver of tumour-bearing rats.
AB  - In rats with advanced malignant disease, the liver extracted circulating
      glutamine at a ratio three times faster than the liver of control non-tumour
      bearing animals. This augmented uptake occurred in spite of a fall in circulating
      glutamine levels, implying an increase in hepatocyte plasma membrane transport.
      Na(+)-dependent glutamine transport activity (System N) was increased nearly two
      fold in hepatocyte plasma membrane vesicles from tumour-bearing rats; this
      increase in System N activity was proportional to tumour size and was due to an
      increase in carrier Vmax with no change in carrier affinity. Measurement of
      System N activity in isolated hepatocytes incubated with serum from tumour
      bearing rats demonstrated a significant increase in glutamine transport compared
      with cells incubated with serum from control rats. These data indicate that the
      liver of rats with advanced malignant disease displays accelerated glutamine
      consumption. This increased uptake is due, in part, to enhanced carrier-mediated
      transport activity, and is mediated by a circulating factor(s) that is not
      present (or inactive) in non-tumour-bearing controls.

PMID- 8252211
TI  - Laparoscopic staging of Hodgkin's disease.
AB  - The role of operative staging of patients with Hodgkin's disease continues to
      evolve. First described in 1969, the indications for this procedure continue to
      be redefined. Recent advances in surgical instrumentation have allowed procedures
      such as cholecystectomy, colon resection, nephrectomy, and splenectomy to be
      performed laparoscopically. We report a case of a complete staging procedure for
      Hodgkin's disease including splenectomy, performed laparoscopically. The patient
      had an uneventful recovery and returned to work 11 days postoperatively. While
      performing this operation laparoscopically does not alter the indications for the
      procedure, laparoscopic staging of Hodgkin's disease may result in shorter
      hospitalization and recovery time while providing complete pathologic staging of
      subdiaphragmatic disease.

PMID- 8252212
TI  - Effect of 5-HT3 receptor antagonist (ondansetron) on functioning human pancreatic
      carcinoid cells.
AB  - 5-Hydroxytryptamine (5-HT) is a mitogen for selected cell types. We have reported
      that 5-HT is an autocrine growth factor for functioning human pancreatic
      carcinoid (BON) cells; autocrine growth effect is transmitted by 5-HT1A but not 5
      HT1C/2 receptors, activation of which decreases cyclic AMP production through a
      pertussis toxin-sensitive inhibitory GTP-binding protein. In this study, the
      effect of 5-HT3 receptor antagonist, ondansetron, on BON was examined.
      Ondansetron did not affect growth of BON cells and also affected neither
      stimulation of phosphatidylinositol hydrolysis or inhibition of cyclic AMP
      production evoked by 5-HT in BON cells. Ondansetron, however, inhibited
      mobilization of intracellular calcium evoked by 5-HT. Present findings suggest
      that BON cells possess 5-HT3 receptors, but their roles in pancreatic carcinoid
      cells are still unknown.

PMID- 8252213
TI  - Inhibition of interleukin-2 dependent immune responses by serum from patients
      with advanced gastrointestinal cancer.
AB  - Immunotherapy with high-dose interleukin-2 (IL-2) fails to induce clinical
      responses in patients with advanced gastrointestinal cancer, but may be effective
      in patients with malignant melanoma or renal adenocarcinoma. The hypothesis that
      this failure may be related to immunosuppressive moieties present in patients
      with advanced gastrointestinal cancer was investigated. Serum samples from 93
      patients (32 advanced gastrointestinal cancer, 22 localized gastrointestinal
      cancer, 13 melanoma/renal adenocarcinoma and 26 age-matched controls) were
      incubated with peripheral blood lymphocytes from healthy volunteers. The
      generation of cytolytic lymphokine-activated killer (LAK) cells and the
      allogeneic mixed lymphocyte response (MLR) were measured in-vitro. LAK effector
      cytotoxicity (mean % +/- SEM) was significantly (P < 0.05) decreased by serum
      from advanced gastrointestinal cancer patients (30 +/- 3) compared with that from
      controls (47 +/- 3), serum from patients with localized gastrointestinal cancer
      (49 +/- 2) or that from patients with melanoma or renal adenocarcinoma (51 +/-
      2). MLR responses were also significantly (P < 0.05) decreased using advanced
      gastrointestinal cancer patients serum compared to controls. A dose-response
      phenomenon for suppression of MLR was observed. Serum from patients with melanoma
      or renal adenocarcinoma was not significantly different to control samples. The
      immunosuppressive properties of serum from patients with advanced
      gastrointestinal carcinoma may abrogate therapeutic attempts using IL-2.

PMID- 8252214
TI  - Differential expression of platelet derived growth factor-beta in malignant
      mesothelioma: a clue to future therapies?
AB  - Malignant mesothelioma (MM) is resistant to most standard forms of treatment.
      Accordingly, novel therapies based on the genetic and autocrine growth
      characteristics are being investigated. Platelet-derived growth factor (PDGF), a
      potent mitogen for mesenchymal cells, is produced by several human malignant cell
      lines including MM and therefore may promote tumourigenesis by an autocrine
      mechanism. We investigated the expression of PDGF-beta mRNA in tumour specimens
      excised from 18 patients with MM. Total cellular RNA was successfully extracted
      from 16/18 frozen tumour specimens with guanidine isothiocyanate and purified by
      centrifugation through a caesium chloride gradient. Northern blots were prepared
      and probed sequentially with 32P-labelled PDGF-beta and beta-actin cDNA. Gene
      expression was quantitated by optical densitometry. Freshly elutriated human
      peripheral blood monocytes were stimulated to induce PDGF-mRNA expression with
      transforming growth factor-beta-1. This positive control was assigned an
      expression index (EI) of 1, with the EI for the tumour sample calculated as:
      PDGFpatient/Actinpatient/EI positive control. In the 16 tumour specimens with
      useable RNA, transcripts for PDGF-beta MRNA were detected. Northern blot analyses
      revealed elevation of PDGF-beta expression above control in 10/16 (63%) of MM
      patients. A 230% increase in PDGF-beta expression (EI = 1.62 vs. EI = 0.49) was
      found between the lowest and highest expression samples. The specimens from which
      the PDGF transcripts were derived were found histologically to contain 87% tumour
      and 13% contaminating normal cells, predominantly lymphocytes. The elucidation of
      the transcriptional regulation of growth factors which are implicated in the
      pathogenesis of MM may guide the development of more effective biologic
      therapies.

PMID- 8252215
TI  - Production of immunosuppressive factors by a cultured tumour cell line and their
      effect on lymphocyte proliferation and cell cycle response.
AB  - Immunosuppression observed in patients with malignancy may be due to factors
      released by tumour cells. Medium conditioned by COLO 205 cells was found to
      inhibit mitogen-stimulated lymphocyte proliferation. Examination of CD25 and
      Class II MHC induction on PBMC incubated in complete, or COLO 205 conditioned,
      medium was not significant. The prevalence of lymphocytes in the S-phase of the
      cell cycle was enhanced after mitogenic stimulation and addition of COLO 205
      conditioned medium. This was balanced by a concomitant fall in proportion of
      cells in the G0/G1 phases of the cell cycle. The immunosuppressive properties of
      COLO 205 conditioned medium was abrogated by heating to 60 degrees C for 30 min
      and by digestion with trypsin. Fractionation of the medium by gel filtration
      yielded two immunosuppressive fractions with relative molecular weights of 60,000
      and below 20,000. It was concluded that cultured COLO 205 cells produce
      immunosuppressive protein/peptide factors which block cell proliferation during
      DNA synthesis. These factors fail to prevent upregulation of membrane-associated
      markers of cell activation.

PMID- 8252216
TI  - Multiple primary carcinoma of the oesophagus.
AB  - A retrospective evaluation of 239 patients with primary oesophageal carcinoma who
      underwent oesophagectomy without preoperative treatment revealed 45 cases (18.8%)
      of multiple primary oesophageal carcinoma (MPEC). The average age of the patients
      with MPEC was significantly lower than that of patients with single primary
      oesophageal carcinoma (SPEC) (P = 0.005). The incidence of association with
      pharyngeal malignancy was higher in patients with MPEC than in those with SPEC (P
      = 0.080). The number of patients in the category representing a combination of
      heaviest alcohol and cigarette use was significantly higher in the MPEC patients
      (P = 0.035). The high incidence of MPEC points to a need for careful checking of
      the oesophagus at the time of surgical treatment for oesophageal carcinoma. Low
      age at onset, a combination of heavy smoking and drinking, and association with
      pharyngeal malignancy are considered to be high-risk factors for MPEC.

PMID- 8252217
TI  - Laparoscopic Billroth II gastrectomy: a review.
AB  - The operation of Billroth II gastrectomy has not changed substantially in concept
      or technique since it was first performed in 1885 by Theodor Billroth. The advent
      of stapling has made the procedure faster for the surgeon but the operation has
      remained as painful and as traumatic for the patient. The totally intra-abdominal
      laparoscopic Billroth II gastrectomy offers a minimally invasive option that is
      remarkably less traumatic and more 'patient friendly'. Initial experience in this
      operation around the world has largely concentrated on resection for benign
      gastric ulcer but the possibility of resection for cancer is not inconceivable.
      Experience with a small experimental series of eight cases showed that this
      operation has many advantages over open surgery in terms of postoperative pain,
      quicker mobilization, fewer wound problems, better cosmesis and quicker
      discharge. No anastomotic leak, chest or wound complications were encountered.
      The main problem remains the cost of disposable stapling devices.

PMID- 8252218
TI  - Laparoscopy for staging in pancreatic carcinoma.
AB  - Pancreatic cancer is the gastrointestinal malignancy with the worst prognosis. At
      the time of diagnosis, only 15% of patients are resectable (and potentially
      curable), 40% have localized but unresectable tumours, and 45% distant
      metastases. Computerized tomography, angiography, and laparoscopy allow for
      adequate staging in this neoplasm. The latter is useful for identifying the small
      (1-2 mm) peritoneal and liver implants which, in our experience, are present in
      27% of patients with tumours of the pancreatic head and in 65% of those with
      cancers of the body and tail of the pancreas. Peritoneal cytology may also be
      performed at the time of laparoscopy, and will be positive for malignant cells in
      20-30% of cases indicating a bad prognosis.

PMID- 8252219
TI  - Endoscopic subtotal oesophagectomy for cancer using the right thoracoscopic
      approach.
AB  - The technique of right thoracoscopic oesophagectomy and our experience with this
      approach are reviewed. The procedure enables resection of middle and lower third
      tumours with lymphadenectomy which is equivalent to that achieved by the standard
      McKeown operation. Thoracoscopic inspection with biopsy detects small pleural
      deposits which are missed by the standard preoperative tests including CT
      scanning. The initial experience with endoscopic oesophagectomy has been
      favourable in terms of recovery and time spent in the intensive care unit,
      although the procedure takes significantly longer than the equivalent open
      dissection of the thoracic oesophagus.

PMID- 8252220
TI  - Laparoscopic hepatic sonography.
AB  - Laparoscopic hepatic sonography is becoming a standard procedure with the arrival
      of specifically designed probes. The technique of liver exploration used in open
      surgery has to be adapted. The technique we propose is initiated by a sagittal
      sonography associated with rotation movements. The basic exploration follows
      firstly the hepatic veins and then the portal branches. During the period of
      vascular exploration, the corresponding liver parenchyma is examined. As the
      quality of the laparoscopic sonography is becoming equivalent to that observed in
      open surgery, in the near future the results of laparoscopic and open surgery
      sonography will probably be identical.

PMID- 8252221
TI  - Laparoscopic colorectal resection for cancer: the Cleveland Clinic Florida
      experience.
AB  - Since the first successful laparoscopic cholecystectomy was performed in 1987,
      surgeons have begun to focus their attention on more diverse procedures. The last
      few years have brought a tremendous amount of enthusiasm toward laparoscopic
      surgery, which has finally reached the colorectal surgical communities.
      Currently, laparoscopic bowel surgery is undergoing critical appraisal. Through
      meaningful prospective data retrieval, answers are being obtained to questions
      dealing with the efficacy and utility of this technique for colorectal diseases.
      Specifically, although laparoscopic colorectal surgery is feasible, one cannot
      definitively attest to its superiority or even equivalence to standard open
      laparotomy. Furthermore, it will take 5 years before we begin to collect data
      regarding survival rates and local recurrence for the patient with colorectal
      carcinoma. This article discusses the technique utilized, and our own experience
      with laparoscopic colorectal surgery for malignancy.

PMID- 8252222
TI  - Experience with laparoscopic colorectal surgery for malignant disease.
AB  - Laparoscopic or laparoscopic-assisted surgery for colorectal cancer was attempted
      in 59 patients suffering from malignant disease of the anus, rectum and colon
      over a 20-month period. Conversion to open surgery was necessary in 5 patients
      (8.4%). The peroperative (30-day) mortality was 5.8%, and in two of the three
      patients who died this was attributable to thrombo-embolic complications. The
      cancer-related mortality was 8%. There were 5 Dukes' A, 21 Dukes' B and 25 Dukes'
      C lesions resected, and thus far all recurrences were in patients who had Dukes'
      C lesions. The resection margins and lymph node yield in these specimens were
      similar to those achieved with conventional open surgery. Six patients also had
      hepatic metastases recognized at the time of primary surgery. These preliminary
      data indicate the feasibility of performing laparoscopic-assisted resection of
      colorectal cancer without compromising the accepted principles of excisional
      surgery for malignant disease. However, a number of important issues such as
      thrombo-embolic prophylaxis, specimen retrieval and the long-term recurrence
      rates require further study before these procedures are widely adopted for
      colorectal cancer.

PMID- 8252223
TI  - Laparoscopic lymphadenectomy in genitourinary malignancies.
AB  - Laparoscopic pelvic lymphadenectomy has been applied to stage prostate cancer
      since 1989. These same laparoscopic techniques are being used to stage other
      urological malignancies. This report will detail the role of laparoscopic
      lymphadenectomy in staging genitourinary malignancies.

PMID- 8252224
TI  - Laparoscopic hysterectomy and cancer.
AB  - Laparoscopic hysterectomy with or without oophorectomy is a procedure which is
      now gaining popularity in the UK. It has been clearly demonstrated that this
      technique is superior to abdominal hysterectomy and oophorectomy via laparotomy,
      and often replaces this procedure. In cases where vaginal hysterectomy is likely
      to prove difficult or impossible in the hands of most surgeons, the laparoscopic
      route is of value. In those cases where dense pelvic adhesions or poor vaginal
      access exist, or where oophorectomy is co-indicated, laparoscopic surgery
      converts operation via laparotomy to a less invasive procedure, with consequent
      benefits in terms of both patient care and bed occupancy. In the case of
      malignant disease, laparoscopic hysterectomy and oophorectomy is a viable
      alternative to open abdominal hysterectomy, but great care must be taken that
      patients with malignant disease are not under-treated.

PMID- 8252225
TI  - Buerger's disease: a review and update.

PMID- 8252226
TI  - Nonatherosclerotic claudication.
AB  - Lower extremity claudication typically reflects the presence of significant
      atherosclerotic arterial obstructive disease. However, a group of
      nonatherosclerotic conditions may cause similar symptoms and a keen appreciation
      of these unusual conditions is essential for the fully trained vascular surgeon.
      Typical atherosclerotic risk factors may or may not be present among patients
      with nonatherosclerotic claudication. However, the astute vascular surgeon can
      diagnose these nonatherosclerotic conditions with a carefully focused history and
      physical examination followed by optimally selected noninvasive testing and
      imaging studies. Once accurately diagnosed, effective and durable treatments are
      generally available for this heterogeneous group of patients.

PMID- 8252227
TI  - Elevated plasma homocysteine as a risk factor for atherosclerosis.

PMID- 8252228
TI  - Heritable arteriopathy.

PMID- 8252229
TI  - Raynaud's syndrome and small vessel arteriopathy.

PMID- 8252230
TI  - The hypercoagulable states: diagnosis and management.

PMID- 8252231
TI  - Postoperative graft surveillance using color-flow duplex.

PMID- 8252232
TI  - The hemodynamics of vein graft stenosis.

PMID- 8252233
TI  - Revision of the failing vein graft: outcome of secondary operations.
AB  - Infrainguinal vein bypass continues to be widely accepted as providing effective
      palliation for disabling claudication and limb salvage in patients with arterial
      insufficiency of the lower extremity. The development of lesions that may
      threaten vein graft patency are presently an inevitable consequence of arterial
      reconstruction in the atherosclerotic patient. However, long-term patency has
      been sustained by detection and intervention for inflow, outflow, or intrinsic
      graft lesions. The excellent secondary (assisted primary) patency rates achieved
      for both reversed and in situ vein grafts affirm the importance of a noninvasive
      surveillance protocol and a low threshold for reintervention before actual graft
      failure.

PMID- 8252234
TI  - Is there a role for percutaneous transluminal angioplasty for graft stenosis?

PMID- 8252235
TI  - Recognition and management of the failing polytetrafluoroethylene (PTFE) graft.

PMID- 8252236
TI  - Infrainguinal graft surveillance: a biased overview.

PMID- 8252237
TI  - The failing graft: an evolving concept.

PMID- 8252238
TI  - Mechanisms of vein graft failure: the location, distribution, and characteristics
      of lesions that predispose to graft failure.

PMID- 8252239
TI  - Essentials of graft surveillance.

PMID- 8252240
TI  - In situ bypass: technical considerations. Overview: history and evolution of
      techniques.

PMID- 8252241
TI  - In situ bypass: technical considerations. Preoperative evaluation of veins.

PMID- 8252242
TI  - In situ bypass: technical considerations. The current Albany approach.

PMID- 8252243
TI  - In situ saphenous vein bypass open technique.

PMID- 8252244
TI  - In situ vein bypass using the intraluminal K.V. Hall valve disruption technique.

PMID- 8252245
TI  - Angioscopic control of in situ bypass: technical considerations.

PMID- 8252246
TI  - Nonreversed translocated vein bypass.

PMID- 8252247
TI  - Lesser saphenous vein used in situ for distal arterial bypasses.

PMID- 8252248
TI  - Additional techniques for the application of the in situ bypass.

PMID- 8252249
TI  - Current follow-up protocol for in situ bypass.

PMID- 8252250
TI  - Perspectives in reparative surgery for acquired valvular disease.

PMID- 8252251
TI  - Double-outlet right ventricle: a surgical synthesis.

PMID- 8252252
TI  - Cardiopulmonary bypass in the neonate.

PMID- 8252253
TI  - Coronary sinus retroperfusion for myocardial protection: pragmatic observations
      and caveats based on a large experience.

PMID- 8252254
TI  - Noninvasive imaging for the diagnosis and management of myocardial ischemia.
AB  - The past 10 years has seen a revolution in noninvasive cardiac imaging. UFCT and
      MRI can demonstrate cardiac anatomy in exquisite detail and have become our most
      accurate methods of measuring ventricular function. PET and MRS are giving
      insights into myocardial metabolism that were previously impossible in vivo. UFCT
      and MRI have also made progress in imaging the coronary arteries and bypass
      grafts. Although neither technique is in a position to rival coronary
      arteriography, the first steps have been made. Accurate quantification of
      coronary calcium is possible with UFCT and promises to be our most valuable
      noninvasive tool in the diagnosis and management of patients with asymptomatic
      disease. Myocardial perfusion has been assessed with 201TL imaging for years, but
      new radiopharmaceutical agents and advances in UFCT and contrast-enhanced MRI are
      likely to bring great improvements. Table 2 lists the current modalities and
      outlines their main advantages and disadvantages. Despite all this progress,
      there has been little change in clinical practice. Invasive procedures, i.e.,
      cardiac catheterization or transesophageal echocardiography, are still being
      performed even when equivalent information can be obtained noninvasively. While
      limited availability may explain the scant use of PET and UFCT for cardiac
      imaging, in those centers where it is available, interest is still muted. The
      need to foster multidisciplinary interaction is real. If the benefits of this
      revolution are to be passed on to patients, there needs to be a greater
      willingness among physicians from different specialties to collaborate and to be
      more tolerant than has occurred in many centers to date. This will not only
      improve patient care but it will also provide an appropriate evaluation of new
      technologies. All are critical if we are to solve the continuing problems of
      ischemic heart disease.

PMID- 8252255
TI  - Dynamic cardiomyoplasty.
AB  - In end-stage heart failure marked by progressive impairment of myocardial
      function, enlarged chamber size, and excessive workload, dynamic cardiomyoplasty
      may have a direct role in improving the mechanical conditions of the left
      ventricle and increasing its contractility on a long-term basis. The chronic use
      of positive inotropic drugs; e.g., amrinone and milrinone, in end-stage
      cardiomyopathy has not been beneficial because of the severely limited
      contractile reserve of the heart and progressive myocardial cell damage related
      to extreme workloads and disadvantaged myocardial energetics. In contrast,
      dynamic cardiomyoplasty enhances left ventricular contractility with an extrinsic
      energy source (the muscle wrap), and in theory, at decreased levels of myocardial
      oxygen requirement because of associated workload reduction. These conceptual
      advantages are supported by the functional and mechanical data from the
      laboratory. Although clinical experience with the procedure is still largely
      experimental, dynamic cardiomyoplasty may have an important future role in the
      treatment of end-stage congestive heart failure.

PMID- 8252256
TI  - HIV and other viruses in surgery: a continued occupational risk.
AB  - Hepatitis viruses and HIV represent known and suspected occupational risks to
      surgeons. A better understanding of these diseases will allow surgeons to provide
      better and more compassionate care for their patients. It is essential that
      surgeons view blood as a toxic substance in the operating room. Reducing
      potential risks can be achieved best by improvement of operating room barriers,
      modification of techniques used in operations, and a prompt response when blood
      contact or exposure occurs. Mandatory or socially imposed voluntary testing for
      HIV testing for patients and physicians (1) is unnecessary; (2) is expensive; and
      (3) continues the socio-political debate about this disease. It is time for HIV
      to be treated like a disease and not a social pariah. To do otherwise will result
      in denial of care for patients and will result in yet another adversarial issue
      to be interposed between surgeons and patients.

PMID- 8252257
TI  - Chronic pulmonary embolism.

PMID- 8252258
TI  - Surgical treatment of thoracic aortic aneurysms.

PMID- 8252259
TI  - Issues surrounding spinal cord protection.
AB  - In summary, paraplegia following procedures on the thoracic and thoraco-abdominal
      aorta is an unpredictable and dreadful complication of multifactorial origin.
      However, it appears that the major causes of immediate post-operative paraplegia
      are the depth and duration of ischemia during the period of aortic cross-clamping
      and failure to identify and reimplant critical vessels that supply blood to the
      spinal cord. Delayed paraplegia, which has been reported to occur from 1 to 21
      days after surgery, is most commonly caused by postoperative hypotension. We
      believe that the final approach to the prevention of paraplegia following
      procedures on the thoracic aorta will be one that involves the use of a technique
      to assure oxygenation of the spinal cord during aortic cross-clamping, through an
      alternate vascular tree, along with a method that can uniformly depict critical
      vessels that must be reimplanted at the time of surgery.

PMID- 8252260
TI  - The role of the contractile fibroblast in the capsules around tissue expanders
      and implants.
AB  - The occurrence, structure and contractility of myofibroblasts in the capsules
      around tissue expanders and static implants has been studied in the rat, pig and
      humans. The capsules showed a characteristic layered structure with
      myofibroblasts being the predominant cell type. Capsular strips contract in vitro
      in a manner characteristic of fibroblast contraction. The contractile ability
      decreased with the time since expander insertion; and increased with expander
      exposure, peri-expander infection and clinical evidence of adverse capsular
      contracture. An hypothesis is proposed that capsular contracture is analogous to
      wound contraction, and that intraimplant pressure usually inhibits capsular
      contraction. Evidence is shown from intraexpander pressure measurements to
      support this hypothesis. The clinical implications for tissue expansion and
      breast augmentation are discussed.

PMID- 8252261
TI  - Repair of mixed peripheral nerves using muscle autografts: a preliminary
      communication.
AB  - Twelve patients were reviewed following the reconstruction of mixed motor/sensory
      nerves using freeze-thawed skeletal muscle autografts. A total of 13 nerves were
      reconstructed-6 median and 7 ulnar. All the repairs were secondary procedures,
      with a mean time from injury to grafting of 17 months. Sensory and motor
      evaluation was carried out and the patients asked to complete a pain
      questionnaire. Five patients achieved an S3+ level of sensory recovery. Two
      underwent revision of their muscle grafts to nerve grafts. Motor recovery was
      universally poor.

PMID- 8252262
TI  - Mechanical properties of skin graft wounds.
AB  - In female Wistar rats the mechanical strength development of the wound between a
      skin graft and the neighbouring intact skin (graft wound) was compared with that
      of ordinary incisional wounds after 4, 7, 14 and 21 days of healing. In one group
      of rats a 35 x 20 mm skin graft including the subcutaneous muscle was raised and
      replaced in situ on the left side of the back and a 35 mm incisional wound was
      made on the right side. In another group a 35 mm incisional wound was made on the
      right side of the back only. After 4 days the maximum load, maximum stiffness and
      relative failure energy of the graft wounds were 49, 43 and 40% less respectively
      than those of the incisional wounds from the same animals and after 7 days the
      maximum load and maximum stiffness of the graft wounds were reduced by 26 and
      29%. However, after 14 and 21 days no differences in mechanical properties were
      found between these two types of wounds. Compared with the incisional wound from
      rats without graft the maximum load, maximum stiffness and relative failure
      energy of the graft wound were reduced by 57, 58 and 44% after 4 days, 59, 62 and
      54% after 7 days, 37, 38 and 29% after 14 days and for maximum load and maximum
      stiffness a reduction of 33 and 31% was found after 21 days of healing.

PMID- 8252263
TI  - The functional and structural effects of hypothermic storage on ischaemic
      arterial grafts.
AB  - The effects of hypothermic ischaemia on blood vessels are unknown. This study
      aimed to determine the 3 week patency rate and the pathology of 9 experimental
      groups of hypothermically stored ischaemic arteries and one control group in a
      rabbit femoral artery model. Ischaemia times were 0 h, 24 h, 1, 2, 4, 6, 8 and 10
      weeks (Groups 1-8). Patency was over 80% in all groups after 3 weeks reinsertion.
      Following reinsertion control grafts maintained normal arterial structure, but
      cellular degeneration had occurred in all ischaemic grafts and appeared complete
      after 4 weeks ischaemia. The graft connective tissue framework frequently
      remained intact. Repair was evident in central graft regions after 2 weeks
      ischaemia and 3 weeks reinsertion, but occurred only adjacent to the anastomosis
      in 4-10 week ischaemic arteries. Four week ischaemic arteries (Groups 9 and 10)
      reinserted for 6 and 12 weeks respectively exhibited near complete repair but
      patency dropped to 60% in the 12 week group.

PMID- 8252264
TI  - Release of Ofloxacin from silicone gel sheet.
AB  - From a drug delivery system using silicone gel, the amount of Ofloxacin (OFLX)
      released or transferred to a wound and blood was measured over 2 weeks. From
      three types of silicone gel containing 2, 0.2 and 0.02% OFLX respectively, levels
      from that with 2% OFLX were highest, approximately two to five times higher than
      that with 0.02% OFLX. Statistically significant differences were found between
      the three types (P < 0.01, Student's t-test). When used in partial thickness skin
      wounds on rats, only an extremely small amount of OFLX was detected in the serum,
      being higher under gel containing 2% OFLX. In a clinical study, however, no drug
      was detected either in the blood or the wound after 1 week.

PMID- 8252265
TI  - The relationship between time of application of prostaglandin E1 and improved
      flap survival.
AB  - Using 60 Hirosaki hairless rats, the relationship between the time of starting
      topical administration of Prostaglandin E1 using silicone gel and flap survival
      rate is described. Compared to control groups, beginning the administration of
      PGE1 at 0 (P < 0.01) and 3 h (P < 0.05) after flap elevation resulted in an
      increased flap survival area (Student's t-test). However, in groups in which PGE1
      administration was begun at 6, 9 and 12 h after flap elevation, no statistically
      significant differences could be detected.

PMID- 8252266
TI  - The use of cerium nitrate-silver sulphadiazine as a topical burns dressing.
AB  - Infection remains the major cause of morbidity and mortality following the shock
      phase in the burn patient. Measures to reduce the risk of wound infection and
      subsequent sepsis include early excision where possible, and the use of topical
      antimicrobial creams such as silver sulphadiazine. Studies from the USA and
      Europe suggest the addition of cerium nitrate to this commonly used agent may
      improve its efficacy. We present the findings of a pilot study which investigated
      the action of a commercial preparation of cerium nitrate/silver sulphadiazine
      mixture (Flammacerium, Duphar B. V. Holland) on 20 patients considered unsuitable
      for surgery. There were no episodes of cellulitis or septicaemia. Flammacerium
      was noted to produce an adherent eschar that was easy to shave and which received
      split skin grafts well.

PMID- 8252267
TI  - A comparative burn wound model in the New Yorkshire pig for the histopathological
      evaluation of local therapeutic regimens: silver sulfadiazine cream as a
      standard.
AB  - A standard burn wound model was developed in the pig to enable evaluation of
      histopathological parameters of wound healing under different circumstances.
      Wounds on one flank were treated with silver sulfadiazine 1% cream (SSD,
      Flammazine-Duphar), which is a standard treatment. On identical places of the
      contralateral side different topical agents were applied. From the SSD treated
      burns a typical histopathologic picture of wound healing under SSD could be
      derived: SSD has the potential to preserve viable dermal tissue, epidermal
      regeneration is rather slow and irritated, while the formation of granulation
      tissue is pronounced, with an abundance of myofibroblasts.

PMID- 8252268
TI  - Omentum as gliding material after extensive forearm tenolysis.
AB  - Tendon adhesion occurring after major replantation can be severe and extensive
      due to the nature of the trauma, ischaemia, prolonged oedema and/or infection.
      Therefore there is a high possibility of re-adhesion after tenolysis. In two
      cases of tenolysis after forearm replantation omentum was used as gliding
      material and good results were obtained.

PMID- 8252269
TI  - Pretibial injuries in the elderly: a prospective trial of early mobilisation
      versus bed rest following surgical treatment.
AB  - Pretibial lacerations are a common form of injury of the elderly population. With
      respect to graft healing, controversy exists regarding rehabilitation by early
      ambulation, following debridement and split skin grafting. In a prospective,
      randomised trial comparing early mobilisation (n = 21) with the traditional
      method of a period of in-patient bed rest after surgical treatment (n = 40), no
      statistically significant difference has been found in the percentage area of
      skin graft take at either 1 or 3 weeks postoperatively. The method of anaesthesia
      (local or general) has no significant effect on the outcome of healing. Prolonged
      bed rest has a detrimental effect on return to independent mobility in one third
      of cases. Complications related to the wound site are similar in both groups.
      Hospital stay averaged 12 days in those confined to bed, compared to an average
      of 2 days in those who were allowed to walk immediately.

PMID- 8252270
TI  - Mohs surgery of basal cell carcinoma--a critical review.
AB  - Mohs surgery for basal cell carcinoma (BCC) of the skin attempts to ensure
      complete tumour removal by histological examination of the entire excision margin
      and further excision of involved sites. Advocates recommend its use in recurrent
      or incompletely excised tumours, poorly defined, histologically aggressive or
      large primary tumours and BCCs situated at high risk or cosmetically important
      sites. The claimed advantages over other surgical therapies are that it provides
      a better chance of cure and since less normal tissue is removed the simpler
      surgical repair ensures a superior cosmetic result. This review examines the
      published evidence that supports the enthusiasm for the use of Mohs surgery in
      the treatment of BCC, contrasting cure rates and cosmetic outcome with results
      achieved by attempted single complete excision and examines the 2 principles upon
      which Mohs surgery is based, namely that BCCs spread by contiguous growth and
      that all tumour cells have to be destroyed to achieve a cure.

PMID- 8252271
TI  - A study of thin (< 1.5 mm) malignant melanomas with poor prognosis.
AB  - 555 cases of malignant melanoma less than 1.5 mm in depth were studied. 30
      recurred locally or metastasised during follow-up. The width and depth of
      excision was similar in those with and without recurrence. There were no local
      recurrences in tumours < 1.0 mm which had been completely excised, irrespective
      of the width of excision. Other variables, the size of the primary tumour (p <
      0.03), the depth of uninvolved dermis deep to the lesion (p < 0.01), the Clark
      level (p < 0.03) and the presence of lesional regression (p < 0.001), identify a
      sub-group of thin melanomas which have a poor prognosis irrespective of local
      treatment.

PMID- 8252272
TI  - A preliminary report on a strategy for treatment of male pattern baldness:
      bilateral vertical flaps plus tissue expansion.
AB  - A strategy of surgical treatment for male pattern baldness has been conceived
      using a combination of flaps and tissue expansion. This strategy has been tested
      on ten cases and the results presented herein. Based on the early experience
      guidelines have been formulated which allow reliability and predictability of
      results, as well as selection of appropriate patients.

PMID- 8252273
TI  - Early repair of unilateral cleft lip employing a small triangular flap method and
      primary nasal correction.
AB  - We describe a technique for early unilateral cleft lip and nose repair in the
      neonatal period which we have used successfully in 84 cases. Some other children
      have had the same method used at a later time. The method has some advantages
      which we believe are particularly useful in neonatal repair.

PMID- 8252274
TI  - A new technique to anastomose vessels with great discrepancy in diameter.
AB  - Free flap transfer often involves anastomosing vessels with different diameters.
      A new technique to anastomose vessels with considerable discrepancy in diameter,
      which has been used reliably for thirteen years in clinical practice, is
      described. Scanning electron microscopy shows that the anastomotic area is very
      smooth and heals well.

PMID- 8252275
TI  - The use of a styrofoam cup in leeching replanted digits.

PMID- 8252276
TI  - Compressive plastic splint for postoperative management of the ear.
AB  - A new splint for use after ear reconstruction is described. This splint adjusts
      suitably to the complicated contours of the ear without requiring any impressions
      before fabrication. The splint controls expansion and contractile forces and
      consequently prevents some of the complications following ear surgery.

PMID- 8252277
TI  - Xanthogranulomatous sialadenitis, a benign mimic of malignancy.

PMID- 8252278
TI  - The use of a toothbrush to debride facial wounds.

PMID- 8252279
TI  - Thromboembolic prophylaxis.

PMID- 8252280
TI  - Psychiatric injury after Hillsborough.

PMID- 8252281
TI  - Attachment theory: a biological basis for psychotherapy?
AB  - John Bowlby bemoaned the separation between the biological and psychological
      approaches in psychiatry, and hoped that attachment theory, which brings together
      psychoanalysis and the science of ethology, would help bridge the rift between
      them. Recent findings in developmental psychology have delineated features of
      parent-infant interaction, especially responsiveness, attunement, and modulation
      of affect, which lead to either secure or insecure attachment. Similar principles
      can be applied to the relationship between psychotherapist and patient--the
      provision of a secure base, the emergence of a shared narrative
      ('autobiographical competence'), the processing of affect, coping with loss-
      these are common to most effective psychotherapies and provide the basis for a
      new interpersonal paradigm within psychotherapy. Attachment theory suggests they
      rest on a sound ethological and hence biological foundation.

PMID- 8252282
TI  - Epilepsy and schizophrenia.
AB  - Slater's work on the schizophrenia-like psychoses of epilepsy is re-examined in
      the light of subsequent developments in psychiatry and neurology. Simple causal
      links of the sort he postulated between epilepsies and psychoses appear
      increasingly tenuous, despite indications that some psychotic symptoms and some
      localised structural changes are linked. A resumption of the study of
      electrophysiological similarities between schizophrenia and limbic epilepsy may
      offer a useful alternative programme for research.

PMID- 8252284
TI  - "A special defence": a psychiatric approach to formalizing euthanasia.
AB  - Domestic and world opinion is gradually changing towards the idea of tolerating
      or even legalizing active euthanasia. The implications of this are examined using
      Foulke's concept of the 'levels' in group discussions. Psychiatrists have a
      unique experience in using the statutory mental health legislation, in addition
      to the ordinary law, to regulate medical care. A new 'special defence' is
      suggested, to be enacted by Parliament, intended to justify, but also designed to
      control, deliberate acts of medical euthanasia.

PMID- 8252283
TI  - Epilepsy and psychiatric disturbance. A cross-sectional study.
AB  - One hundred patients with cryptogenic epilepsy and normal intelligence and 100
      age- and sex-matched controls were submitted to psychiatric interview using the
      Clinical Interview Schedule. Nineteen patients and 15 controls were identified as
      having psychiatric disorders. Anxiety and depression were the predominating
      diagnoses in both groups. Personality disorders were occasionally present in
      subjects with epilepsy. The study shows that patients with cryptogenic epilepsy
      and normal neuropsychological abilities should not be considered at any higher
      risk of psychiatric disturbance than a non-neurological patient population.

PMID- 8252285
TI  - Incidence of dementia in a representative British sample.
AB  - In a four-year follow-up study of 1042 elderly people (aged 65 years or older),
      randomly sampled from the community, levels of dementia were assessed using a two
      phase case-finding procedure (screening followed by clinical interview) among
      survivors. Clinical information on those not reinterviewed was provided by death
      certificates, hospital case notes, or postal questionnaires. The weighted four
      year cumulative incidence of dementia was 3.7% (95% confidence intervals: 2.4%
      5.0%), with age-specific rates of 0.9%, 2.8%, 5.2%, 9.0%, and 8.7% for the age
      groups 65-69, 70-74, 75-79, 80-84, and 85-89 years respectively. While consistent
      with data from other British regions, it remains likely that these rates
      underestimate true incidence.

PMID- 8252286
TI  - Psychiatric morbidity in older people with moderate and severe learning
      disability. I: Development and reliability of the patient interview (PAS-ADD).
AB  - This paper describes the development of the PAS-ADD, a semistructured clinical
      interview for use specifically with patients with learning disabilities, based on
      items drawn from the PSE. The PAS-ADD includes a number of novel features
      including: parallel interviewing of patient and informant; a three-tier structure
      to provide a flexible interview appropriate to the patient's intellectual level;
      use of a memorable 'anchor event' in the patient's life to improve time focus;
      and simplified wording, improved organisation and lay out. Inter-rater
      reliability was investigated using an experimental design in which two raters
      viewed and re-rated videotaped PAS-ADD interviews which had been conducted by an
      experienced clinician. Reliability results compared favourably with those
      obtained in a major study of PSE reliability with a sample drawn from non
      learning disabled individuals. Mean kappa for all items was 0.72. Other indexes
      of reliability were also good. In the current phase of development, the PAS-ADD
      is to be expanded to include further diagnostic categories, including
      schizophrenia and autism. The new version will be updated for use with ICD-10
      criteria.

PMID- 8252287
TI  - Psychiatric morbidity in older people with moderate and severe learning
      disability. II: The prevalence study.
AB  - We present a prevalence study of psychiatric morbidity in people over 50 years of
      age with learning disability (LD), using a new semistructured clinical interview
      specifically for use with people who have LD (the 'PAS-ADD'). Assessment involved
      parallel interviewing of subject and informant, these two sets of information
      being combined to reach a final diagnosis using ICD-9 and DSM-III-R criteria.
      Detection of dementia involved interviews with informants, plus investigation of
      loss of cognitive function over a three-year period. The experimental sample was
      a mixed community and institutional group (n = 105), including, as far as
      possible, all people in a single administrative district (Oldham) matching the
      age and ability criteria. Prevalence of psychiatric disorder excluding dementia
      was 11.4% (n = 12), most of which were depression and anxiety. Seventy-five per
      cent of these cases were unknown to mental health services. However, immediate
      care staff were usually aware of the symptoms, although often unaware of their
      clinical significance. Prevalence of dementia was also 11.4% (n = 12), with a
      combined case prevalence of 21.0% (n = 22). The PAS-ADD proved a flexible
      interview, effective in use with people of varying linguistic level and
      intellectual ability: 61.9% (n = 65) of the sample were able to be interviewed,
      fully adequate clinical interviews being obtained with a group of 38 people whose
      mean IQ was only 39. In the remaining 38.1% (n = 40), diagnosis relied
      exclusively on informant data. Overall, the combination of subject and informant
      data was essential for sensitive case detection.

PMID- 8252288
TI  - Familial psychiatric illness and obstetric complications in early-onset affective
      disorder. A case-control study.
AB  - Early-onset affective disorder is associated with obstetric complications and a
      high familial risk of psychiatric illness, in particular psychosis. In a matched
      case-control study, we investigated 47 adult in-patients with major depressive
      disorder or bipolar 1 disorder, who had earlier in life presented to a child
      psychiatry department. Cases were matched on sex, social class and ethnic group
      with 47 controls, who were admitted to hospital for affective disorders in adult
      life but had no psychiatric contact before the age of 21. We found that both
      psychiatric disorder in first-degree relatives and a history of obstetric
      complications were associated with early onset. Childhood symptoms did not
      predict the type of adult affective disorder.

PMID- 8252289
TI  - Childhood sexual experiences with adults. A comparison of reports by women
      psychiatric patients and general-practice attenders.
AB  - Reports of childhood sexual experiences with adults were collected from 120 women
      attending general-practice surgeries and 115 women psychiatric patients. The
      method of study, research team and county of residence were the same for the two
      groups. The psychiatric patients tended to report rates of events higher than the
      general-practice attenders by a factor of 2-3. The results suggest an association
      between such experiences and later psychiatric patienthood and are compatible
      with a causal role for them in some cases.

PMID- 8252290
TI  - Psychopathology and quality of life among mentally ill patients in the community.
      British and US samples compared.
AB  - Sixty-nine mentally ill patients in treatment in an intensive community support
      system in Boulder, Colorado, were evaluated using the same measures of quality of
      life and psychopathology as were used in assessing mentally ill patients in
      hospital and community facilities in Manchester. Psychopathology was greater in
      the Boulder samples, but quality-of-life scores were no worse for the American
      patients. The relationship of these findings to systems of care and availability
      of psychiatric hospital beds is discussed.

PMID- 8252291
TI  - Psychosocial dysfunction in somatising patients.
AB  - Somatising patients present with a variety of psychosocial dysfunctions. Using
      the Dysfunctional Analysis Questionnaire and the Global Assessment of Functioning
      scale, we studied the nature and severity of psychosocial dysfunction in a group
      of somatising patients. Dysfunction was less marked in the cognitive area than in
      social, vocational, personal and familial areas. Patients with depressive
      disorders showed more dysfunction than those with somatoform disorders in all
      psychosocial areas except cognitive.

PMID- 8252292
TI  - Is there a lithium withdrawal syndrome? An examination of the evidence.
AB  - The evidence for abstinence phenomena after discontinuation of lithium is weak
      and ambiguous. Early manic and depressive recurrences after lithium
      discontinuation may suggest rebound, but studies carried out with appropriate
      methodology have failed to confirm its reality. Discontinuation of prophylactic
      lithium treatment of recurrent manic-depressive illness, whether abrupt or
      gradual, involves risk of relapse, but the existence of a special lithium
      withdrawal syndrome remains unproven.

PMID- 8252293
TI  - Epidemiological evidence that maternal influenza contributes to the aetiology of
      schizophrenia. An analysis of Scottish, English, and Danish data.
AB  - The epidemiological evidence that the offspring of women exposed to influenza in
      pregnancy are at increased risk of schizophrenia is conflicting. In an attempt to
      clarify the issue we explored the relationship between the monthly incidence of
      influenza (and measles) in the general population and the distribution of birth
      dates of three large series of schizophrenia patients--16,960 Scottish patients
      born in 1932-60; 22,021 English patients born in 1921-60; and 18,723 Danish
      patients born in 1911-65. Exposure to the 1957 epidemic of A2 influenza in
      midpregnancy was associated with an increased incidence of schizophrenia, at
      least in females, in all three data sets. We also confirmed the previous report
      of a statistically significant long-term relationship between patients' birth
      dates and outbreaks of influenza in the English series, with time lags of -2 and 
      3 months (the sixth and seventh months of pregnancy). Despite several other
      negative studies by ourselves and others we conclude that these relationships are
      probably both genuine and causal; and that maternal influenza during the middle
      third of intrauterine development, or something closely associated with it, is
      implicated in the aetiology of some cases of schizophrenia.

PMID- 8252294
TI  - McHugh's "A structure for psychiatry at the century's turn--the view from Johns
      Hopkins".

PMID- 8252295
TI  - Dangerous behaviour preceding first admissions for schizophrenia.

PMID- 8252296
TI  - d-fenfluramine and cognitive therapy in bulimia nervosa.

PMID- 8252297
TI  - Diagnostic agreement in psychiatry.

PMID- 8252298
TI  - Diagnostic agreement in psychiatry.

PMID- 8252299
TI  - Importance of stratification by age.

PMID- 8252300
TI  - Sporadic Pick's disease.

PMID- 8252301
TI  - Patient's perception of family emotional climate.

PMID- 8252302
TI  - Down's syndrome, dementia, and superoxide dismutase.

PMID- 8252303
TI  - Home-based acute psychiatric services.

PMID- 8252304
TI  - Small babies and schizophrenia.

PMID- 8252305
TI  - Depression of old age.

PMID- 8252306
TI  - Ageing as a risk factor for lithium neurotoxicity at therapeutic serum levels.

PMID- 8252307
TI  - Double firing of ECT machine.

PMID- 8252308
TI  - Higher risk groups and paracetamol overdose.

PMID- 8252309
TI  - The International League of Associations for Rheumatology and the information
      deficit.

PMID- 8252310
TI  - Insulin-like growth factor stimulation of articular chondrocyte proteoglycan
      synthesis. Availability and responses at different ages.
AB  - It was found that recovery of articular chondrocyte proteoglycan (PG) synthesis
      was retarded in old mice after in vivo exposure to both IL-1 or hydrogen
      peroxide. We examined whether this could be related to diminished serum levels of
      insulin-like growth factor 1 (IGF-1), the main anabolic factor, or to changes in
      cartilage IGF responsiveness with age. A small decline of IGF-1 concentration was
      observed in serum of old mice, but the level still appeared to be supra-optimal
      to maintain normal cartilage PG synthesis over a culture period of 1 to 3 days.
      Moreover, PG synthesis was at least equally stimulated in patellar cartilage from
      18-month-old mice compared to 3-month-old mice over a wide range of IGF-1
      concentrations, and similar findings were obtained after stimulation with serum.
      In addition, we studied the capacity of IGF-1 or serum to induce recovery of PG
      synthesis in vitro after IL-1 exposure in vivo. In a 3-day culture period normal
      cartilage PG synthesis was stimulated to the same extent with serum or IGF-1, but
      recovery from IL-1 mediated suppression of PG synthesis was more pronounced with
      serum. This latter capacity was similar for serum of mice aged 3 or 18 months and
      was noted for both young and old cartilage. Our data show that retarded recovery
      of chondrocyte PG synthesis in old mice cannot be explained by age-related
      changes in IGF-1 availability and cartilage responses to IGF. They also indicate
      that serum factors other than IGF-1 are important for recovery, either alone or
      in combination with IGF-1.

PMID- 8252311
TI  - Virus-like particles in synovial fluids from patients with rheumatoid arthritis.
AB  - Based on the elevated expression of oncogenes in proliferating transformed
      appearing synoviocytes we searched for the possible involvement of a viral agent
      in the pathogenesis of RA. We report the detection of virus-like particles with
      retroviral C type morphology in SF, which lack the typical morphologic as well as
      immunohistochemical features of the human T-lymphotropic and immunodeficiency
      viruses.

PMID- 8252312
TI  - Effect of dietary fish powder on intestinal flora and development of arthritis in
      the pig.
AB  - In 1971 Mansson et al. reported that a 20% dry fish powder diet fed to young pigs
      induced arthritis and increases in faecal Clostridium perfringens counts. To
      confirm this interesting finding we have repeated their experiment by following
      their regimen as closely as possible. Twelve piglets of Finnish landrace were
      divided at 8 weeks of age into two groups according to litter, sex and initial
      weight. The control group received a cereal-based diet. In the experimental group
      20% of cereal in the diet was replaced by fish meal. Stool samples were cultured
      for Cl. perfringens and subjected to direct gas-liquid chromatography (GLC) to
      provide bacterial cellular fatty acid profiles. Development of arthritis was
      monitored macroscopically, and synovial samples were taken at autopsy for
      microscopical examination. Faecal Cl. perfringens counts increased 10-40 times
      more in the fish diet group than in the control group. GLC revealed a significant
      difference in bacterial florae between the groups. No arthritis was observed and
      only slight synovial inflammation in four experimental pigs and in one control
      pig. We conclude that fish diet changed faecal flora significantly, but did not
      induce arthritis.

PMID- 8252313
TI  - Cytokine and prostaglandin production by monocytes of volunteers and rheumatoid
      arthritis patients treated with dietary supplements of blackcurrant seed oil.
AB  - In this study, dietary supplements of blackcurrant seed oil (BCO) rich in the n-6
      polyunsaturated fatty acid (PUFA) gamma-linolenic acid were fed to both RA
      patients and healthy volunteers with sunflower seed oil being fed to control
      subjects. A significant improvement in morning stiffness was noted in the RA
      patients receiving BCO. Monocytes were isolated from all subjects and cultured in
      the presence of lipopolysaccharide. It was observed that the production from the
      cultured monocytes of the cytokines IL-1 beta, TNF alpha and IL-6 as well as the
      prostaglandin PGE2 was markedly altered in those subjects given BCO. The results
      suggest that the numerous beneficial effects of PUFAs in inflammatory diseases
      such as RA may be due to a reduction in the secretion of the inflammatory
      cytokines IL-1 beta and TNF-alpha via redirection of eicosanoid metabolism
      although the possibility cannot be excluded that the PUFAs may be altering
      cytokine release directly through an effect on monocyte membranes.

PMID- 8252314
TI  - Primary generalized osteoarthritis and bone mass.
AB  - The association of OA with increased bone mass is controversial. This study
      measured BMD at the hip and spine and total body bone mineral (TBBM) by dual
      energy X-ray absorptiometry, and BMD at the distal forearm by single photon
      absorptiometry in 20 post-menopausal women with primary generalized OA. The data
      were compared with those from 89 normal controls. Osteoarthritic women had
      significantly increased BMD at the spine (P < 0.001), distal forearm (P < 0.05)
      and increased TBBM (P < 0.01), but no difference was seen at the femoral neck.
      These differences were not explained by obesity. The influence of mobility is
      discussed.

PMID- 8252315
TI  - Nailfold capillary circulation in osteoarthritis.
AB  - Nailfold capillaries in 28 patients with OA affecting the distal interphalangeal
      joints were compared to 23 age- and sex-matched controls without OA. Patients
      with OA showed a significantly lower density of capillaries in their nailfolds
      and significantly more capillary morphological abnormalities including
      haemorrhage, 'drop out', dilatation and irregularity. There was a trend for OA
      patients to have warmer fingers with reduced finger to brachial blood pressure
      ratios. There were significant correlations between nailfold capillary numbers
      and average joint tenderness and between capillary morphological changes and
      joint swelling. These results reveal a relationship between interphalangeal joint
      OA and nailfold capillary abnormalities and density. As changes in
      microcirculation may be pertinent to the pathogenesis of OA, further studies
      which could explore possible causal relationships are warranted.

PMID- 8252316
TI  - Zygapophyseal and costovertebral/costotransverse joints: an anatomic assessment
      of arthritis impact.
AB  - Zygapophyseal articular surface cortical disruption noted radiologically in RA is
      at variance with the perception that it is an axial joint-sparing (cervical
      vertebrae excepted) disorder. However, the reliability of such radiologic
      assessment has been questioned. Direct visual examination of the zygapophyseal
      and costovertebral joints (of individuals with documented RA,
      spondyloarthropathy, diffuse idiopathic skeletal hyperostosis and normal
      controls) allowed these radiologic perceptions to be tested and placed in
      perspective. Articular surface cortical disruption/discontinuity was actually
      found to take two forms, indistinguishable by standard X-ray technique: 1. fronts
      of resorption, with reactive new bone formation; 2. exposed bare trabeculae,
      secondary to a 'wearing away' abrasion process. Zygapophyseal and costovertebral
      erosions were only found in skeletons of individuals with spondyloarthropathy,
      whereas the abrasion-related phenomenon was especially prevalent in RA and in
      normal controls. Inability to radiologically distinguish abraded or 'worn away'
      lesions from erosions explains past radiologic confusion. Radiologic evidence of
      zygapophyseal and costovertebral joint surface disruption/discontinuity does not
      appear specific for erosive disease.

PMID- 8252317
TI  - Sleep disturbances in patients with primary Sjogren's syndrome.
AB  - A standardized sleep questionnaire was used to investigate the sleeping habits of
      outpatients with primary Sjogren's syndrome (pSS) (n = 40) and RA (n = 42). Sleep
      deficit (difference between need of sleep and actual sleeping time) was
      significantly higher in patients with pSS when compared with healthy matched
      controls (P < 0.0001), and with patients suffering from RA (P < 0.001). When
      trying to fall asleep, patients with pSS were significantly more often disturbed
      by muscular tension (45%) and restless legs (24%), than patients with RA (12%, P
      < 0.01 and 2%, P < 0.01), and they were also significantly more troubled by
      nocturnal pain than patients with RA (P < 0.01). The pSS group reported
      significantly more disturbing by awakening during the night and was awake for
      longer periods than the RA group. Fatigue was a significantly more frequent
      complaint in patients with pSS. Polysomnography showed that all recorded patients
      (n = 10) had some sleep disturbances; reduced sleep efficiency (n = 8), increased
      number of awakenings (n = 5) and increased wakefulness surrounded by sleep (n =
      9). Five patients had alpha intrusion in their sleep EEGs. The sleep disturbances
      seen in patients with primary Sjogren's syndrome may contribute to the fatigue
      associated with this disease.

PMID- 8252318
TI  - Additive effect of combined naproxen and paracetamol in rheumatoid arthritis.
AB  - The clinical effect and plasma naproxen levels were studied in 20 patients with
      RA receiving three doses of naproxen and two naproxen doses combined with
      paracetamol (acetaminophen) in a randomized, double-blind, comparison in five 2
      wk treatment periods. A significant dose-concentration effect relationship was
      found for the three naproxen doses (500, 1000 and 1500 mg daily). The following
      variables were measured: global clinical effect, joint index, morning stiffness,
      activity of daily living (ADL), pain during movement and at rest. The naproxen
      dose-concentration effect relationship curve was moved to the left by the
      addition of 4 g paracetamol daily. No major side effects were observed, but
      complaints concerning the gastrointestinal tract were fewer on lower naproxen
      doses and these were not increased by concomitant paracetamol treatment. The
      results show that the clinical effect of naproxen in RA may be significantly
      increased by concomitant paracetamol administration.

PMID- 8252319
TI  - The mobility outcome for amputees with rheumatoid arthritis is poor.
AB  - This study examines the reasons for amputation of the lower limb in 11 patients
      with RA. The reasons for amputation were ischaemia due to peripheral vascular
      disease; rheumatoid vasculitis; or complications of knee arthroplasty. Delayed
      healing was common in patients on steroid therapy. The patients had difficulty
      donning and doffing their prostheses due to poor hand function and impaired
      agility. Walking training and rehabilitation were slow and tended to precipitate
      a generalized flare-up of disease activity. Rheumatoid nodules developed on
      pressure points between stump and socket. Despite these problems the majority of
      patients preferred to wear a prosthesis for help in transferring in and out of
      the wheelchair, to complete their appearance and for limited mobility. Most found
      using an electric powered indoor wheelchair helped maintain their independence.

PMID- 8252320
TI  - Synovectomy of the hand.

PMID- 8252321
TI  - Reiter's syndrome after intravesical Bacillus Calmette-Guerin treatment for
      superficial bladder carcinoma.
AB  - A 64-year-old woman developed acute Reiter's syndrome 4 weeks after the start of
      intravesical Bacillus Calmette-Guerin immunotherapy for a recurrent superficial
      bladder carcinoma. The absence of any other cause suggests that the bacillus
      played an etiopathogenic role in this HLA-B27-positive patient.

PMID- 8252322
TI  - Monoarthritis caused by Mycobacterium avium complex in a liver transplant
      recipient.
AB  - A 38-yr-old liver transplant recipient presented with a monoarthritis caused by
      Mycobacterium avium complex (MAC). Diagnosis was not obtained with repeated
      microscopy and culture of SF aspirate, and required synovial biopsy.

PMID- 8252323
TI  - Idiopathic recurrent non-suppurative focal myositis: a report of two cases.
AB  - We describe two patients with acute recurrent focal myositis affecting discrete
      muscle groups. Sepsis was initially suspected in both cases and excluded only
      after surgical intervention. Spontaneous remissions occurred and extensive
      investigations have not demonstrated a precipitating cause.

PMID- 8252324
TI  - Transverse myelitis as the presentation of Jo-1 antibody syndrome (myositis and
      fibrosing alveolitis) in long-standing ulcerative colitis.
AB  - A 32-yr-old woman with long-standing ulcerative colitis developed paraesthesiae,
      sensory loss and muscle weakness shown by magnetic resonance scan to be due to
      transverse myelitis in the cervical spinal cord. More than 12 months later, she
      developed dermatomyositis and fibrosing alveolitis and was found to have the Jo-1
      antibody. Her condition worsened despite high dose oral prednisolone but improved
      following intravenous methylprednisolone, immunosuppressive therapy and plasma
      exchange. This is the first reported case of a neurological presentation of the
      Jo-1 antibody syndrome. We speculate that the association with ulcerative colitis
      may have been causal rather than coincidental and suggest that plasma exchange
      should be considered together with aggressive immunosuppression in seriously ill
      patients with this disease.

PMID- 8252325
TI  - D-penicillamine and polymyositis: the significance of the anti-Jo-1 antibody.
AB  - A 57-yr-old lady developed polymyositis whilst taking D-penicillamine for RA. D
      Penicillamine-induced polymyositis occurs in RA with a greater frequency than
      idiopathic polymyositis. Anti-acetyl choline receptor antibodies and ANA were
      positive, consistent with drug-induced disease. Anti-Jo-1 antibodies are
      considered specific for idiopathic myositis, and their presence was unexpected.
      Following withdrawal of the drug, the disappearance of the anti-Jo-1 and other
      antibodies coincident with clinical improvement, suggested that D-penicillamine
      was responsible for inducing antibody production.

PMID- 8252326
TI  - Cogan's syndrome and Peyronie's disease: a non-fortuitous association.

PMID- 8252327
TI  - Chlamydia pneumoniae as a cause of reactive arthritis.

PMID- 8252328
TI  - Urate crystal test in Behcet's syndrome.

PMID- 8252329
TI  - Clinical spectrum of synovitis-acne-pustulosis-hyperostosis-osteomyelitis
      syndrome.

PMID- 8252330
TI  - Efficacy and safety of radiation synovectomy with Yttrium-90: a retrospective
      long-term analysis of 164 applications in 82 patients.

PMID- 8252331
TI  - Childhood arthritis--the name game.

PMID- 8252332
TI  - Chronic lupus peritonitis responsive to treatment with cyclophosphamide.

PMID- 8252333
TI  - Silicone breast prostheses and rheumatic disorders.

PMID- 8252334
TI  - Frequency of alleles of type II collagen in collagen antibody-positive rheumatoid
      arthritis patients.

PMID- 8252335
TI  - A comparative study of serum deaminases in systemic rheumatic diseases.

PMID- 8252336
TI  - Screening for abdominal aortic aneurysm.

PMID- 8252337
TI  - Surgical options for primary hepatocellular carcinoma.

PMID- 8252338
TI  - Hepatocyte growth factor/scatter factor, liver regeneration and cancer
      metastasis.
AB  - Hepatocyte growth factor (HGF) is the most potent stimulator of hepatocyte growth
      and DNA synthesis identified; it is now known to be the same molecule as scatter
      factor, which increases the motility of a variety of cell types. HGF is becoming
      recognized as one of the most important factors in the regulation of liver
      regeneration after surgical resection or chemical damage. HGF is produced by
      several tissues, including neoplasms; it can therefore provide a stimulus for
      increased motility of malignant cells by both a paracrine and autocrine
      mechanism. The receptor for HGF has been identified as the product of the
      oncogene c-met, raising the possibility that this gene plays a key role in
      facilitating cellular invasion. HGF may therefore be important not only for liver
      cell growth but also in metastasis. This article summarizes the current position
      of research on HGF, and presents both clinical and scientific evidence that
      strongly implicates this factor in liver regeneration and cancer invasion and
      metastasis.

PMID- 8252339
TI  - 'Bile' in the oesophagus.
AB  - Acid gastro-oesophageal reflux occurs when the lower oesophageal sphincter is
      incompetent, but oesophagitis caused by reflux of duodenal content implies
      incompetence of both the pyloric and gastro-oesophageal sphincters. The term
      'alkaline' reflux oesophagitis was coined long before objective analysis was made
      of bile in the stomach and oesophagus, and well before pH monitoring was
      introduced. Surgical procedures to divert bile from the stomach and oesophagus
      were developed on a clinical basis and gave encouraging results in the management
      of peptic oesophageal stricture. Alkaline oesophagitis is well recognized after
      gastric surgery and the entity 'primary pathological duodenogastric reflux',
      although contested by some, attracts growing support. Recent evidence suggests
      that the complications of Barrett's oesophagus may be related to duodenogastro
      oesophageal reflux. Probes designed to measure gastric and oesophageal bile salts
      have recently been developed and may give more information in the future.

PMID- 8252340
TI  - Organization of general surgical services in Britain: strategic planning of
      workload and manpower. Working Party, Council of the Association of Surgeons of
      Great Britain and Ireland.

PMID- 8252341
TI  - Eye protection for the vascular surgeon.
AB  - Contamination occurring during vascular surgery was studied prospectively using a
      surgical mask incorporating a Splashguard visor. Over a 16-week period 78
      vascular procedures were included; 44 were of < 2 h duration and 34 were of > or
      = 2 h. Contamination on both mask and visor from blood spots was recorded at the
      end of each procedure. Overall, 51 per cent of principal surgeons' visors were
      contaminated, with contamination of the mask itself in 32 per cent. When two
      surgeons were operating the contamination rate for the second was also high: 36
      per cent for the visor and 42 per cent for the mask. Assistants had a
      contamination rate of 36 per cent for the visor and 13 per cent for the mask. The
      lowest rate of contamination occurred for the visor and mask of the scrub nurse,
      10 and 4 per cent respectively. For emergency procedures the duration of
      operation had no influence on the frequency of contamination. However, for the
      principal surgeon elective operations of < 2 h duration were less likely to
      involve contamination than those of > or = 2 h (P < 0.035). Blood contamination
      of visors and masks is common in vascular surgery but rarely appreciated by the
      surgeon. Routine eye protection should be considered in vascular surgery, in
      particular for emergency and prolonged elective procedures.

PMID- 8252342
TI  - Genetic linkage analysis applied to unaffected women from families with breast
      cancer can discriminate high- from low-risk individuals.
AB  - Up to 20 per cent of cases of breast cancer diagnosed in women under the age of
      45 years may be caused by an autosomal dominant gene. A present difficulty is
      differentiation of mutation carriers from non-mutation carriers in high-risk
      families. Genetic linkage analysis has been used to localize a susceptibility
      gene (BRCA1) on chromosome 17q12-21 between markers 42D6 and MFD188, a region 5
      10 million base pairs in length. Odds in favour of linkage to this region were
      greater than 100,000:1 in 15 families with breast cancer. In eight families in
      which the probability of linkage was above 75 (range 79.2-99.9) per cent, 19
      women were identified who were at high lifetime risk of breast cancer (range 80.6
      87.2 per cent) and 37 whose risk was similar to that for the general population
      (range 9.8-16.4 per cent). Genetic risk prediction of this kind may enable high
      risk screening clinic resources to be concentrated on those most likely to
      benefit.

PMID- 8252343
TI  - Significance of circumferential resection margin involvement after oesophagectomy
      for cancer.
AB  - This study examined the influence of tumour involvement of the circumferential
      resection margin on subsequent local recurrence after oesophagectomy. Fifty
      patients were studied: 36 men and 14 women of median age 62 (range 44-83) years.
      Each patient had undergone oesophagectomy at which all macroscopic disease had
      been removed. Pathological specimens were sectioned tangentially at 0.5-1.0-cm
      intervals to permit microscopic examination of the circumferential resection
      margin. Patients were followed and investigated by endoscopy with biopsy and
      imaging techniques only if symptomatic. Twenty of the 50 specimens demonstrated
      involvement of the circumferential resection margin. At median follow-up of 36
      (range 24-52) months, eleven of these 20 patients had developed histologically
      proven local recurrence compared with only four of the remaining 30 in whom the
      resection margin was clear of tumour (P < 0.01). Circumferential spread of
      oesophageal cancer appears to be a significant cause of local tumour recurrence.

PMID- 8252344
TI  - CD4 and CD8 monoclonal antibody therapy: strategies to prolong renal allograft
      survival in the dog.
AB  - The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has
      been demonstrated in rodent transplant models. In this paper the
      immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal
      allografts was evaluated as a preliminary to tolerogenic studies in this large
      animal model. Monoclonal antibodies were given for a maximum of 10 days after
      transplantation. Therapy was stopped prematurely following adverse reactions
      associated with the recipient developing an antibody response against the foreign
      (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8
      antibodies indicated that saturating doses were achieved. Although neither CD4
      nor CD8 alone prolonged allograft survival (rejection by day 7), combination of
      CD4 and CD8 antibodies resulted in good graft function for a median of 14 days.
      The effect of removing circulating T lymphocytes was also assessed using a lytic
      Thy-1 monoclonal antibody. Alone Thy-1 had little effect but, when combined with
      CD4, the median allograft survival time was increased to 15.5 days. Reduction of
      the number of circulating T lymphocytes appears complementary to blockade of CD4
      for immunosuppression, while blockade of CD4 combined with removal of CD8 also
      favours allograft survival.

PMID- 8252345
TI  - Patient selection and timing of dynamic computed tomography in acute
      pancreatitis.
AB  - Dynamic computed tomography (CT) is the most accurate method for determining the
      extent of necrosis in acute pancreatitis. Debate exists, however, regarding
      patient selection and the optimal timing of CT. This study examined selection
      based on biochemical and/or clinical criteria and the influence of delayed
      dynamic CT performed 5-10 days after the onset of an attack. A total of 120
      patients with acute pancreatitis were studied. Dynamic CT was performed if any of
      the following criteria were identified: a biochemically severe attack (according
      to Glasgow criteria) in the first 24 h, C-reactive protein (CRP) level above 120
      mg/l in the first 3 days or failure of clinical resolution within 7 days. Of 42
      patients selected for CT, five died from multisystem organ failure before day 5.
      There were no deaths or delayed complications in the 78 patients not selected for
      scanning. Positive Glasgow criteria alone in the scanned group had a sensitivity
      for predicting necrosis (as recognized by CT) of 22 per cent and a specificity of
      20 per cent. Measurement of CRP level alone had a sensitivity of 26 per cent and
      specificity of 80 per cent. Failure of clinical resolution had a sensitivity of
      only 7 per cent but a specificity of 100 per cent. The combination of Glasgow
      criteria and CRP level had a sensitivity of 44 per cent and specificity of 100
      per cent. Delayed complications (pseudocyst, five; infection, six) occurred only
      in patients with necrosis, and there were two deaths. An 'at-risk' group can be
      identified for CT on the basis of biochemical and clinical observations. Neither
      routine nor emergency dynamic CT in acute pancreatitis seems justified.

PMID- 8252346
TI  - Prospective comparison of laparoscopic and conventional anterior resection.
AB  - A prospective comparison of laparoscopically assisted (n = 11) and conventional
      (n = 14) anterior resection in patients with sigmoid colon or upper rectal cancer
      was carried out. Patients were not randomized; age and the presence of metastases
      determined the type of surgery. Laparoscopic assistance was used to mobilize the
      tumour and minimize the abdominal incision. This was achieved in all patients and
      six of the 11 required only a muscle-splitting incision. The mean(s.d.) operating
      time was longer for laparoscopic than conventional surgery (205(31) versus
      123(26) min, P = 0.01). The mean(s.d.) time to reintroduction of normal diet
      (2.5(0.2) versus 3.6(0.3) days, P = 0.01), postoperative analgesia requirement
      (2.6(0.4) versus 7.4(2.1) doses of pethidine, P = 0.01) and length of hospital
      stay (12.3(3) versus 14.3(6) days, P = 0.08) were less in the laparoscopic group.
      Histopathological examination of the resection specimens showed similar results
      for the two procedures. Major complications were few and occurred in a similar
      proportion of patients treated laparoscopically or conventionally.
      Laparoscopically assisted anterior resection is technically feasible, adequate
      tumour excision can be achieved and recovery after operation is enhanced.

PMID- 8252347
TI  - Faecal occult blood screening for colorectal neoplasia in a targeted high-risk
      population.
AB  - A general practice-based programme was initiated in 1987 to identify individuals
      at high risk of developing large bowel cancer and offer them screening of faecal
      occult blood. In all, 5298 people from 21 general practices in the Guildford area
      were offered 7510 screening tests. In total, 5934 tests were completed
      (compliance rate 79.0 per cent) with 287 positive results (4.8 per cent). Of the
      patients with positive results, 44 had cancer and 38 polyps. The sensitivity of
      the test for cancer was 63 per cent, the specificity 96 per cent and the positive
      predictive value for all neoplasia 29 per cent. The detection rate of 44 cancers
      per 5934 people screened compares favourably with data from the Nottingham-based
      screening of an unselected population (0.74 versus 0.23 per cent).

PMID- 8252348
TI  - Long-term survival after endoscopic transanal resection of rectal tumours.
AB  - The outcome and survival of 120 consecutive patients of median age 78 years with
      rectal tumours who underwent endoscopic transanal resection were assessed. Thirty
      eight patients (32 per cent) were treated for large villous adenoma. These
      patients underwent a median of 2 (range 1-5) resections and the overall 5-year
      survival rate was 78.2 per cent. Of 82 patients with rectal cancer, 33 (28 per
      cent of the 120) had tumours amenable to conventional surgery but for the
      patient's age or infirmity. The 5-year survival rate of these patients was 29.7
      per cent. Endoscopic transanal resection was used to palliate the symptoms of 49
      patients (41 per cent) with rectal cancer; the 5-year survival rate was 13.7 per
      cent. Excellent long-term outcome may be achieved with endoscopic transanal
      resection for patients with benign rectal tumours. This approach also gives
      acceptable results for selected patients with rectal cancer in whom age, extent
      of disease or concurrent illness preclude conventional surgical resection.

PMID- 8252349
TI  - D-dimer: a useful marker of disease stage in surgery for colorectal cancer.

PMID- 8252350
TI  - Ultrasonographic screening for abdominal aortic aneurysm in an urban community.
AB  - As part of the Birmingham Community Aneurysm Screening Project, 3500 men aged 65
      75 years from 20 urban general practices were invited for aortic ultrasonographic
      screening at their own general practitioner's surgery; 2669 (76.3 per cent)
      attended. Compliance rates varied between catchment areas, from 52.1 per cent for
      inner-city areas to 89.6 per cent for suburbs. Successful aortic imaging was
      achieved in 97.3 per cent of scans. Aortic diameter > 29 mm occurred in 219
      patients (8.4 per cent) and 79 (3.0 per cent) with a diameter > 40 mm were
      referred for vascular surgical assessment; 140 patients with an aortic diameter
      of 29-40 mm are currently undergoing follow-up by serial ultrasonographic
      examinations at intervals of 3 months at their doctor's surgery. Risk factor
      analysis revealed ischaemic heart disease in 21.9 per cent of men with aneurysm,
      compared with 11.6 per cent in those without (P < 0.001); 18.3 per cent of men
      with aneurysm had had a previous myocardial infarction and 13.2 per cent had
      peripheral vascular disease, compared with 7.4 per cent (P < 0.001) and 8.0 per
      cent (P < 0.01) respectively of those without. No association was found between
      aneurysm and hypertension or diabetes. Community-based aortic screening is an
      inexpensive, effective method of diagnosis of aneurysm, with high compliance from
      the at-risk cohort of an urban population. Such screening programmes may help to
      reduce the mortality rate from aortic aneurysm rupture.

PMID- 8252351
TI  - Correlation between p53 mutations and antibody staining in breast carcinoma.
AB  - Abnormalities of the p53 gene and protein were examined in 81 primary breast
      carcinoma samples. Using a polymerase chain reaction-single-strand conformational
      polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in
      13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining
      for p53 protein was detected in ten of 77 (13 per cent) of these tumours using
      polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP
      analysis were more common in grade III tumours (P = 0.015), but no correlation
      was found with tumour size, node status or level of epidermal growth factor
      receptor expression. A p53 mutation was associated with positive antibody
      staining in only two patients. Positive immunohistochemical staining using a p53
      antibody may detect p53 protein expression, but this may not correlate directly
      with an underlying mutation in the hot spot region examined.

PMID- 8252352
TI  - Resting energy expenditure in patients undergoing transhiatal or transthoracic
      oesophagectomy for carcinoma of the thoracic oesophagus.
AB  - Resting energy expenditure (REE) was studied in five patients undergoing
      transhiatal and in 14 undergoing transthoracic oesophagectomy for carcinoma. All
      resections were performed with an intention to cure. REE was measured by indirect
      calorimetry before operation and on days 1, 3, 5 and 7 after surgery. Following
      transthoracic oesophagectomy, REE increased significantly on days 1, 3, 5 and 7
      after operation, and on day 7 the value was significantly higher (P < 0.05) than
      that obtained after transhiatal surgery. Energy expenditure following transhiatal
      oesophagectomy is lower than that after transthoracic oesophagectomy; this may be
      a result of reduced surgical stress.

PMID- 8252353
TI  - Resection-line involvement in gastric cancer: a continuing problem.
AB  - Surgeons are aware of the adverse effect that resection-line disease has on
      anastomotic leakage, perioperative mortality and long-term survival. In an
      attempt to assess the effect of this knowledge on surgical practice, patients
      entered into the second British Stomach Cancer Group adjuvant therapy trial were
      studied. The presence of resection-line disease was compared with the operative
      stage. Of 555 patients for whom complete data were available, resection-line
      disease was present in 105 (19 per cent). Of 424 patients undergoing what the
      surgeon considered to be a potentially curative operation, 55 (13 per cent) had
      involvement of one or both resection lines, rendering the surgery palliative.
      Only 9 per cent of patients with stage I-III disease and resection-line
      involvement survived beyond 5 years, compared with 27 per cent of those with
      clear lines. Despite knowledge of the adverse effects of resection-line disease,
      surgeons continue to perform inadequate resections. This demonstrates the need
      for a more aggressive approach to assessment of resection margins at operation.

PMID- 8252354
TI  - Vertical banded gastroplasty for the treatment of morbid obesity.
AB  - Prospective evaluation of 114 obese patients (96 women, 18 men) undergoing
      vertical banded gastroplasty over a 5-year period was undertaken. The age range
      was 17-58 (median 37) years, median weight 119.3 (range 79-216) kg, mean(s.d.)
      proportion of excess body-weight 104.1 (34.9) per cent and median body mass index
      (BMI) 44.8 (range 33.2-77.7) kg/m2. Three gastric outlet stoma circumferences
      were used: 5.5 cm (31 patients), 5.0 cm (28) and 4.75 cm (55). A total of 109
      patients (95.6 per cent) were available for follow-up. At 1 year after operation,
      54 patients (59 per cent) had lost greater than 50 per cent of excess body
      weight. No patient lost less than 25 per cent of excess body-weight, and the
      median BMI was 32.5 (range 21.3-47.8) kg/m2. The operative mortality rate was
      zero, but three patients (2.6 per cent) with gastric leakage required surgical
      revision. Vertical banded gastroplasty is a relatively safe and simple procedure
      that produces significant and sustained weight reduction in the majority of
      morbidly obese patients.

PMID- 8252355
TI  - Comparative audit: fact versus fantasy.

PMID- 8252356
TI  - Reoperation for biliary tract complications following orthotopic liver
      transplantation.
AB  - Biliary tract complications were analysed after 54 orthotopic liver
      transplantations performed in 49 patients over a 2-year period. Reconstruction of
      the bile duct consisted of end-to-end choledochocholedochostomy over a T tube in
      47 cases and Roux-en-Y choledochojejunostomy in seven (two for sclerosing
      cholangitis, one for secondary biliary cirrhosis, four retransplants). The T tube
      was withdrawn 12-16 weeks after operation in all but two patients (2-3 weeks).
      There was no intraoperative mortality. Eight patients (16 per cent) died during
      the first month and the 1-year actuarial survival rate was 75 per cent. Early
      biliary complications (up to 3 months after operation) consisted of five bilomas,
      for which ultrasonographically guided drainage was effective in three and
      surgical drainage necessary in two. Late biliary complications (3 months onwards)
      consisted of biliary peritonitis following T tube removal (four patients;
      reoperation was required in all four) and necrosis of the bile duct secondary to
      a late arterial thrombosis (one). The incidence of reoperation as a result of
      early biliary complications was low (two patients), but higher for biliary
      peritonitis following T tube removal.

PMID- 8252357
TI  - Liver resection for recurrent hilar cholangiocarcinoma.

PMID- 8252358
TI  - Percutaneous transhepatic cholecystostomy for acute acalculous cholecystitis.
AB  - The effectiveness and long-term results of percutaneous cholecystostomy for acute
      acalculous cholecystitis are evaluated. Fifteen patients with acute acalculous
      cholecystitis were treated prospectively by this procedure, using a pigtail
      catheter successfully placed under ultrasonographic and fluoroscopic guidance.
      Prompt relief of the signs and symptoms of cholecystitis was achieved in 14
      patients. One required emergency cholecystectomy for uncontrolled bleeding after
      drainage. Another patient underwent prophylactic cholecystectomy before further
      chemotherapy for leukaemia. The remaining 13 patients required no further
      surgery. Morbidity and mortality rates were 13 per cent and nil respectively.
      Long-term follow-up showed no recurrence of cholecystitis after removal of the
      catheter. Percutaneous cholecystostomy is a safe, effective and usually
      definitive procedure for the treatment of acute acalculous cholecystitis.

PMID- 8252359
TI  - Temporary use of a biliary endoprosthesis for unsuspected bile duct stones found
      at laparoscopic cholecystectomy.

PMID- 8252360
TI  - Laparoscopic ligation of large pedicles.

PMID- 8252361
TI  - Mucosal morphology, cell proliferation and faecal bacteriology in acute
      pouchitis.
AB  - A study was performed to investigate whether acute reservoir ileitis (pouchitis)
      is associated with specific changes in mucosal morphology, crypt cell kinetics
      and faecal bacteriology in the ileal pouch. Forty-six patients were studied
      (ileal reservoir, 36; end ileostomy, ten) using clinical grading, sigmoidoscopy
      and biopsy; 24 patients with a reservoir were restudied after therapy for 1 month
      with metronidazole 400 mg three times daily. An index of villus atrophy and crypt
      cell production rate (CCPR) were determined in all biopsy material. Faecal
      bacteriology was assessed in 12 patients with a pouch before and after
      metronidazole therapy. The mucosa of patients with pouchitis was associated with
      a lower villus atrophy index (P = 0.052), a higher CCPR (P = 0.03) and a higher
      grade of acute inflammation than that in those without pouchitis. There was no
      difference in faecal bacterial counts between patients with and without
      pouchitis. A low atrophy index correlated with a high CCPR (P < 0.001), worse
      functional score (P < 0.001) and more severe pouch mucosal acute inflammation (P
      < 0.001), but not with faecal bacteriology. Following metronidazole therapy there
      was resolution of acute pouch inflammation, increased villus atrophy index (P =
      0.049), decreased CCPR (P = 0.049) but no differences in faecal bacterial counts
      apart from Bacteroides species. These data show that metronidazole therapy does
      not specifically alter the growth of common faecal bacteria in patients with
      pouchitis, apart from Bacteroides species. However, metronidazole causes
      resolution of the typical changes in pouch mucosal morphology and crypt cell
      kinetics associated with pouchitis.

PMID- 8252362
TI  - One-layer continuously sutured colonic anastomosis.

PMID- 8252363
TI  - Conservative treatment for low rectal carcinoma by local excision with or without
      radiotherapy.
AB  - Thirty-seven patients with low rectal carcinoma were treated by transanal
      resection between January 1979 and December 1988. Adjuvant radiotherapy was used
      in eight patients before operation, in 13 after operation and six patients had
      both preoperative and postoperative radiotherapy. The selection criteria for
      transanal resection were low, superficial tumours treated conservatively with
      curative intent (group 1, 18 patients) or patients medically unfit for (12) or
      refusing (seven) abdominoperineal resection (APR) (group 2, 19 patients). In
      group 1, the local recurrence rate was 11 per cent with an overall 5-year
      survival rate of 100 per cent. In group 2, the local recurrence rate was 53 per
      cent with an overall 5-year survival rate of 35 per cent. There was no
      postoperative mortality and minimal morbidity. Salvage of local failure was by
      APR in six patients. The survival rate after local recurrence was 70 per cent at
      1 year and 30 per cent at 5 years. Transanal resection can be proposed as a
      curative procedure for selected low, small, minimally infiltrating and well
      differentiated adenocarcinomas. Local control might be improved by postoperative
      radiotherapy for Astler-Coller stage B1 tumours or those above 3 cm in diameter.
      Further trials should examine the results of high-dose (60 Gy) preoperative
      radiotherapy so that transanal resection might be employed for favourable post
      irradiation stage (0 or A) lesions. This new strategy will benefit from a better
      evaluation of tumour response after primary radiotherapy and an improved
      assessment of histological excision margins.

PMID- 8252364
TI  - Lymph node metastases in early rectal cancer.
AB  - Local excision of early rectal tumours is an attractive proposition, avoiding the
      morbidity and mortality of major resection and possible permanent stoma. This
      study was designed to investigate the incidence of lymph node metastases
      associated with tumours that are locally confined to the bowel wall. A total of
      454 rectal excision specimens were reviewed. Twenty-two (20 per cent) of 109
      patients with tumours locally confined to the bowel wall had metastases in local
      lymph nodes, although 14 of these had only one or two involved nodes. Three of 27
      patients with tumours that did not penetrate through the submucosa had lymph node
      metastases. Less well differentiated tumours were more likely to have
      metastasized but there was no significant difference in the height or size of
      tumours or in the depth of invasion between patients with or without lymph node
      metastases.

PMID- 8252365
TI  - Herniation at the site of cannula insertion after laparoscopic cholecystectomy.

PMID- 8252366
TI  - Herniation at the site of cannula insertion after laparoscopic cholecystectomy.

PMID- 8252367
TI  - Herniation at the site of cannula insertion after laparoscopic cholecystectomy.

PMID- 8252368
TI  - Laparoscopic cholecystectomy.

PMID- 8252369
TI  - New adjustable knot for securing subcuticular running sutures.

PMID- 8252370
TI  - Return to work after inguinal hernia repair.

PMID- 8252371
TI  - Detection and enumeration of circulating tumour cells in colorectal cancer.

PMID- 8252372
TI  - Vein-patch rupture after carotid endarterectomy: an avoidable catastrophe.

PMID- 8252373
TI  - The organizational concept and vertebrates without sex chromosomes.
AB  - The diversity in vertebrate reproductive patterns provides natural experiments
      that yield new insights into behavioral endocrinology. Discussed here is the
      generality of the concept of an organizing sex during sexual differentiation. In
      its present form the Organizational Concept emphasizes hormonally induced
      organization of the male phenotype, with the female phenotype being the neutral
      or default condition. Does this concept extend to vertebrates lacking genotypic
      sex determining mechanisms? The answer appears to be No. In species with
      temperature-dependent sex determination, each embryo has an equal probability of
      developing into either a male or a female; there is no heritable genetic
      predisposition for sex determination. In species with behavior-dependent sex
      determination, sex-change occurs during adulthood as a result of perceived
      alterations in the social environment. In parthenogenetic species, only female
      individuals exist, yet they display both male-like and female-like "sexual"
      behaviors. In contrast to the contemporary view of the Organizational Concept,
      let us assume that the male pattern is derived and imposed upon the ancestral
      female pattern. If this perspective is taken, several avenues of study are
      identified: (i) the importance of sexual similarities; (ii) extending the
      principle of complementarity of sexual behaviors to the brain; (iii) temperature
      modulation of sexual differentiation, and (iv) the role of the brain in sex
      determination.

PMID- 8252374
TI  - Evolution of gonadotropin-releasing hormone (GnRH) neuronal systems.
AB  - The neuropeptide gonadotropin-releasing hormone (GnRH, LHRH) serves as both a
      hormone and a neurotransmitter, and it has multiple actions on reproductive
      physiology and behavior. At least seven different molecular forms of GnRH have
      evolved, and nearly all vertebrates studied express at least two different forms
      of GnRH: chicken GnRH II, and a second form that varies across classes. The GnRH
      cell bodies span a broad region of the forebrain and midbrain, and processes
      project to virtually every region of the CNS, to the vasculature, and to the
      cerebrospinal fluid. Comparative evidence supports the model that gnathostomic
      vertebrates possess two principle GnRH systems, with different embryonic and,
      probably, evolutionary origins, expressing different molecular forms of GnRH and
      projecting to different targets. The terminal nerve-septo-preoptic system serves
      as the principle regulator of gonadotropin release in most vertebrates. Neurons
      originate in the embryonic olfactory placode and migrate centrally during
      development, and it is proposed that ontogeny of the TN-septo-preoptic system
      reflects its evolutionary origins as a peripheral endocrine organ associated with
      the olfactory system. The second GnRH system, which arises from non-placodal
      precursors, comprises cell bodies in periventricular regions of the posterior
      diencephalon and/or midbrain. Although much less is known about the posterior
      GnRH system, evidence suggests that these cells served as the ancestral brain
      GnRH system and are the cellular locus of the chicken GnRH peptide. The GnRH
      system of lampreys does not appear to be homologous to either the TN-septo
      preoptic or posterior GnRH system, and it is suggested that GnRH in agnathans
      represents a third evolutionary event.

PMID- 8252375
TI  - Sexual differentiation of brain and behavior: the zebra finch is not just a
      flying rat.
AB  - In rats and other mammals, sex differences in the brain and behavior result from
      differential secretions of gonadal steroid hormones during early critical periods
      of neural development. We review the experimental results that support current
      ideas about the mechanisms of sexual differentiation in mammals, and then apply
      the same experimental analysis to the study of sexual differentiation of the
      neural song circuit in the zebra finch (Poephila guttata), a passerine song bird.
      Administration of estrogen to young female zebra finches causes the female to
      develop a more masculine song system and to sing as an adult. This estrogenic
      masculinization is similar to that found for copulatory behavior in mammals.
      However, striking differences emerge in other aspects of the sexual
      differentiation process. Experiments that use endocrine agents to block the
      masculine development in genetic males have so far failed. Moreover, the brain of
      zebra finches has an unusually high expression of aromatase (estrogen synthetase)
      in the telencephalon, and estrogen synthesized in the brain from androgen is
      released into the general circulation. These results suggest that the brain is
      the primary source of estrogen in the body. If so, then a further understanding
      of sexual differentiation requires more information on the factors that regulate
      the cerebral synthesis of estrogen.

PMID- 8252376
TI  - Weakly electric fish as model systems for studying long-term steroid action on
      neural circuits.
AB  - Weakly electric fish generate electric organ discharges (EODs) that are species
      specific and often sexually-dimorphic. The waveform or frequency of an EOD can be
      altered by treating a fish with sex steroid hormones. The EOD is controlled by a
      few discrete nuclei in the brainstem and spinal cord and a muscle-derived
      electric organ. The organizational simplicity and steroid-sensitivity of the
      electromotor system make it a premier system for investigating how sex steroids
      modulate behavior, neural circuitry, and ion channels. In addition, the diversity
      of EOD patterns in the many species of electric fish provide a wealth of material
      in which to examine the evolution of sexual dimorphisms in the nervous system.

PMID- 8252377
TI  - Sensory pathways linking social and environmental cues to endocrine control
      regions of amphibian forebrains.
AB  - The secretion of gonadotropin releasing hormone (GnRH), and hence sex steroids,
      is influenced by social signals produced by conspecifics and by environmental
      cues such as day length. The sensory systems processing these varied signals must
      therefore connect with the GnRH control centers in the preoptic area and
      hypothalamus. Forebrain pathways in frogs provide a model for how vertebrates
      accomplish this. Auditory information, which can transmit the features of the
      vocal communication signals used by frogs during reproductive social behavior,
      reaches both the preoptic area and ventral hypothalamus via thalamic and midbrain
      nuclei. An examination of these auditory pathways suggests that there are subtle
      differences in their anatomical, physiological, and histochemical
      characteristics. The suprachiasmatic nucleus, which is important for controlling
      circadian rhythms in vertebrates, also projects to both the preoptic area and
      ventral hypothalamus, providing information about environmental characteristics
      in parallel with the information about social signals. This pattern of
      connections suggests that the two major GnRH control centers in amphibian brains
      receive independent, parallel information about the social and environmental cues
      influencing reproduction.

PMID- 8252378
TI  - Sex pheromone systems in goldfish: comparisons to vomeronasal systems in
      tetrapods.
AB  - Most amphibians, reptiles and mammals possess a well defined dual olfactory
      system comprised of separate neural pathways that regulate different olfactory
      functions. One pathway originates in the nasal cavity and gives rise to what is
      commonly referred to as the main olfactory system. The other pathway originates
      in the vomeronasal organ (VNO) and gives rise to the accessory olfactory system.
      Functionally, the main olfactory system is thought to subserve, olfactory
      mediated tasks such as feeding and grooming, while the accessory olfactory system
      is believed to be primarily involved in mediating behavioral and physiological
      responses to sex pheromones. Traditionally, it has been difficult to address
      whether teleosts possess any components of the vomeronasal system, since they
      generally do not meet the criteria used to identify vomeronasal systems in other
      vertebrates. Previous conclusions that the nasal epithelia of fish is olfactory
      and not vomeronasal in nature are based on observations that teleosts lack a
      separate VNO-like chemosensory structure and an anatomically distinct accessory
      olfactory bulb. However, because sex pheromones have been identified in the
      goldfish, it is now possible to compare the neural substrates that regulate
      pheromone-induced responses in teleosts to those that mediate similar responses
      in other vertebrates. The olfactory system in goldfish is particularly well
      suited for such comparisons, because it comprises anatomical and functional
      subdivisions that resemble those associated with the main and accessory olfactory
      systems in tetrapods. The olfactory pathways that mediate endocrine and
      behavioral responses to sex pheromones in goldfish are described and then
      compared to the main and accessory olfactory systems of tetrapods. In making
      these comparisons, a number of similarities become apparent. First, the olfactory
      pathways that regulate responses to sex pheromones in goldfish are different from
      those that serve a more general olfactory function. Second, these functional
      differences appear to be subserved by separate and anatomically distinct
      olfactory tract projections to the brain. Third, the lateral olfactory tracts and
      their central projections in goldfish appear to serve a function analogous to
      that of the main olfactory system, while the medial olfactory tracts and their
      central projections comprise a pathway remarkably similar to the vomeronasal
      accessory olfactory system. These findings suggest that teleosts may possess
      functional correlates of tetrapod vomeronasal systems, but in a form that has yet
      to be recognized. If so, medial olfactory tract projections in goldfish may be
      evolutionarily conserved and expressed in tetrapods as the vomeronasal system, or
      the medial olfactory tract projections may be new pathways that have evolved to
      serve the same function.

PMID- 8252379
TI  - Where does damage lead to enhanced food aversion: the ventral pallidum/substantia
      innominata or lateral hypothalamus?
AB  - It is well known that lesions of the lateral hypothalamus (LH) produce aphagia.
      Several previous studies have reported that lateral hypothalamus damage produces
      food aversion in addition to aphagia. However, damage to other regions near the
      LH also produce aphagia and enhanced aversion. The purpose of this study was to
      resolve where the site or sites for aversion-inducing lesions is/are located.
      Small, bilateral excitotoxin lesions (QUIN, 10 micrograms in 1 microliter or IBO,
      15 micrograms in 1 microliter) or bilateral sham injections of vehicle were made
      into the globus pallidus (GP), the ventral pallidum/substantia innominata (VP/SI)
      or the lateral hypothalamus (LH). Affective reactions to taste were elicited by
      infusing sucrose solutions (1 M) into the mouth via chronic oral cannulae. The
      number of aversive responses (gapes, chin-rubbing, head-shaking and forelimb
      flails) emitted was tallied. Individual lesions were mapped and a single
      'necessary and sufficient' site for damage-induced aversion was identified (the
      area of overlapping damage common to all rats that showed enhanced aversive
      reactions). To identify the lesions, two lesion-mapping techniques were used: (1)
      a conventional neuron-counting procedure in which an attempt is made to count all
      neurons within a brain region, and (2) a new modified 'fractionator' procedure
      consisting of exhaustive 400 x magnification counts at point locations within a
      brain region. Results indicated that aversive reactions to food are enhanced only
      following bilateral neuron loss (> 70%) from the caudal ventromedial VP/SI alone.
      This shared site has a lateral diameter of 1.0 mm, a dorsoventral diameter of 0.5
      mm and a rostrocaudal diameter of 1.0 mm. Damage restricted to the LH never
      produced enhanced aversion even when it produced aphagia. The crucial region for
      aversion is located ventral and medial to the globus pallidus and dorsal and
      lateral to the lateral hypothalamus.

PMID- 8252380
TI  - Intracellular calcium changes associated with cholinergic nicotinic receptor
      activation in cultured myenteric plexus neurones.
AB  - Intracellular free calcium concentration ([Ca2+]i) was measured in cultured
      explants of myenteric plexus neurones by using the fluorescent calcium indicator
      Indol in combination with patch-clamp techniques. The basal [Ca2+]i was 94 nM and
      spontaneous oscillations in the internal free calcium concentration were
      recorded. These oscillations were associated with bursts of action potentials
      triggered by spontaneous nicotinic excitatory synaptic potentials. Under voltage
      clamp conditions, application of the selective nicotinic agonist m
      hydroxyphenylpropyl-trimethylammonium iodide (10 microM) induced an inward
      current and increased the intracellular free calcium concentration. We conclude
      that cholinergic synaptic excitatory activity provide a regular calcium entry in
      myenteric neurone and suggest that the nicotinic channel might be significantly
      permeable to calcium.

PMID- 8252381
TI  - Increased spontaneous unit discharge rates following electrical kindling in the
      rat.
AB  - Changes in neuronal excitability that persist after seizures may play a key role
      in epilepsy. In this study, extracellular single unit recording techniques were
      used to investigate the changes in cell discharge patterns that result from
      kindling in vivo. The spontaneous activity of piriform and perirhinal cortical
      units in chronically implanted adult rats was recorded before, during and after
      kindling the amygdala. We observed that kindling-induced seizures resulted in a
      prolonged and dramatic increase in the rate of spontaneous background neuronal
      discharge in both the piriform and perirhinal regions.

PMID- 8252382
TI  - Circadian rhythms of vasopressin release in primary cultures of rat
      suprachiasmatic nucleus.
AB  - We have developed a suprachiasmatic nucleus (SCN) cell culture system to study
      the cellular and molecular bases of the mammalian circadian pacemaker. The SCN
      regions were dissected from 4- to 6-day-old rat pups and dissociated cells were
      cultured in a defined medium. In all the cultures, the release of vasopressin
      showed clear circadian oscillation, which appeared within a few days in culture
      and lasted for more than a month. The peak of vasopressin release was observed at
      subjective day. These findings suggest that this culture system provides a
      valuable model for elucidating the mechanism of the circadian pacemakers.

PMID- 8252383
TI  - beta-Amyloid peptides induce degeneration of cultured rat microglia.
AB  - Microglia are often associated with senile plaques, a primary pathological
      hallmark of Alzheimer's disease (AD) that consists largely of insoluble deposits
      of beta-amyloid (A beta) protein. Synthetic A beta peptides have been shown to
      induce neurite dystrophy and neuronal death in vitro when the peptides are
      assembled into aggregates. We now report that assembled A beta peptides induce
      morphological evidence of degeneration in process-bearing microglia in vitro, as
      well as metabolic dysfunction in microglial cultures, but a non-assembling
      scrambled sequence A beta peptide does not.

PMID- 8252384
TI  - Effects of systemic administration of 6-hydroxydopamine, 6-hydroxydopa and 1
      methyl-4-phenyl-1,2,3,6-tetrahydroxypyridine (MPTP) on tuberoinfundibular
      dopaminergic neurons in the rat.
AB  - Using systemic route of administration, the effects of several neurotoxins on
      hypothalamic tuberoinfundibular dopaminergic neurons were focused in this study.
      6-Hydroxydopamine (6-OHDA, 10 or 100 mg/kg b.wt., i.v. or ip) produced a dose (37
      vs. 50%)- and time (41 to 29% from day 4 to day 9)-dependent depletion of
      hypothalamic median eminence dopamine concentrations, and increases of serum
      prolactin levels in ovariectomized rats. Other central dopaminergic neurons,
      however, were not significantly affected. Similar treatments with 6-hydroxydopa
      (6-OHDOPA) were less effective. On the other hand, treatments of 1-methyl-4
      phenyl-1,2,3,6-tetrahydroxypyridine (MPTP, 10 mg/kg b.wt./day, ip) for 7 or 14
      days produced significant decreases of dihydroxyphenylacetic acid (DOPAC) levels
      in the median eminence and periventricular regions, and increases in serum
      prolactin levels. Other central dopaminergic neurons were not significantly
      affected, though. These results suggest that systemic administration of 6-OHDA, 6
      OHDOPA, or MPTP, can produce specific destructive effects on the
      tuberoinfundibular dopaminergic neurons.

PMID- 8252385
TI  - Human brain methionine- and leucine-enkephalins and their receptors during
      ageing.
AB  - Brain Met- and Leu-enk levels were investigated with radioimmunoassay and their
      binding to enkephalin receptors was studied with [3H]Met- and [3H]Leu-enkephalin
      in 56 human subjects (4-93 yr). Of the brain areas investigated, the head of the
      caudate nucleus and pallidum showed an age-associated decline for both Met- and
      Leu-enk content. In the substantia nigra and in putamen, no significant age
      effect was seen. Binding of the enkephalins, which was studied in the head of the
      caudate nucleus and hippocampus, did not show significant age dependency. In
      conclusion, ageing affects human brain enkephalin levels but not their receptor
      binding, at least in brain areas investigated in the present study.

PMID- 8252386
TI  - [Leu5]enkephalin-like immunoreactive amacrine cells are under nicotinic
      excitatory control during darkness in chicken retina.
AB  - Based on the principle that retinal levels of [Leu5]enkephalin-like
      immunoreactivity (LELI) are set by the rate of release and thus reflect neural
      activity, we partially defined the dark-associated increase in excitatory control
      of LELI amacrine cells in chicken. Retinal levels of LELI were measured by
      radioimmunoassay (RIA). Intravitreal injection of cholinergic antagonists
      decreased the rate of depletion of LELI during the dark phase, suggesting the
      presence of cholinergic excitatory control of the LELI neurons. This cholinergic
      control involves nicotinic rather than muscarinic receptors, as tubocurarine
      appeared over 100 times more effective than atropine in inhibiting the decrease
      in retinal levels of LELI in the dark. (The ED50s were estimated at 3.2 and 450
      nmol, respectively.) The lack of effect of the antagonists when applied during
      the light phase, suggest that there is little cholinergic input to the LELI
      amacrine cells in the light. Superfusing isolated retinas with buffer containing
      tubocurarine (10 microM) decreased the efflux of LELI by 35%, compared to the
      spontaneous release during the dark. Atropine (10 microM) had no effect on the
      release of LELI, and pilocarpine (100 microM) increased the release of LELI from
      retinas superfused in the light by 20%. We conclude that, in addition to
      previously reported glycinergic and dopaminergic inhibition, the LELI amacrine
      cells receive cholinergic excitatory input. A shift in balance between
      glycinergic and dopaminergic inhibitory, and cholinergic excitatory control may
      underly the light-driven variation in activity of the LELI neurons in chicken
      retina.

PMID- 8252387
TI  - Medullary mu and delta opioid receptors modulate mesencephalic morphine analgesia
      in rats.
AB  - Supraspinal opioid analgesia is mediated in part by connections between the
      midbrain periaqueductal gray (PAG) and rostral ventral medulla (RVM) which
      includes the nuclei raphe magnus and reticularis gigantocellularis. Serotonergic
      5HT2 and 5HT3 receptor subtypes appear to participate in this pathway since
      general and selective serotonergic antagonists microinjected into the RVM
      significantly reduced morphine analgesia elicited from the PAG. Since both an
      enkephalinergic pathway between the PAG and RVM and intrinsic enkephalinergic
      cells in the RVM exist, the present study evaluated the abilities of general
      (naltrexone), mu-selective (beta-funaltrexamine: B-FNA) and delta 2-selective
      (naltrindole) opioid receptor subtype antagonists microinjected into the RVM to
      alter morphine (2.5 micrograms) analgesia elicited from the PAG as measured by
      the tail-flick and jump tests. Mesencephalic morphine analgesia was significantly
      reduced after pretreatment in the RVM with naltrexone (1-10 micrograms), B-FNA
      (0.5-5 micrograms) or naltrindole (0.5-5 micrograms). Naltrexone in the RVM
      failed to alter basal nociceptive thresholds and none of the opioid antagonists
      were effective in reducing mesencephalic morphine analgesia when they were
      microinjected into placements lateral or dorsal to the RVM. These data indicate
      that mu and delta 2 opioid receptors in the RVM modulate the transmission of
      opioid pain-inhibitory signals from the PAG.

PMID- 8252388
TI  - Chelation of zinc by diethyldithiocarbamate facilitates bursting induced by mixed
      antidromic plus orthodromic activation of mossy fibers in hippocampal slices.
AB  - The effect of chelation of zinc by diethyldithiocarbamate (DEDTC) on bursting of
      CA3 pyramidal cells induced by mixed antidromic plus orthodromic activation of
      mossy fibers (MP) in hippocampal slices was studied. Slices perfused in
      artificial cerebrospinal fluid (ACSF) with high (2.5 mM) Ca2+ rarely exhibited
      triggered bursting following a series of stimulus trains similar to those used in
      kindling. In contrast, slices perfused with DEDTC (0.1 mM) in ACSF and
      subsequently perfused with ACSF alone prior to initiating the stimulus trains
      exhibited robust triggered bursting following the stimulus trains. However, if
      slices perfused with ACSF containing DEDTC were then perfused with ACSF
      containing zinc chloride (0.5 microM) followed by ACSF alone, triggered bursting
      was not induced subsequent to delivering stimulus trains. It is concluded that
      release of zinc from the mossy fibers induced by tetanic stimulation serves to
      obtund bursting in CA3 pyramidal cells.

PMID- 8252389
TI  - Synergistic brainstem interactions for morphine analgesia.
AB  - Morphine is a potent analgesic when microinjected into the periaqueductal gray
      (PAG), the rostral ventral medulla (RVM) which contains the nuclei raphe magnus
      and reticularis gigantocellularis and the dorsolateral pons (DLP) which includes
      the locus coeruleus. Coadministration of low morphine doses which are inactive
      alone into combinations of these three regions elicits dramatic analgesic
      responses, implying the existence of synergy. The most effective combination is
      the PAG/RVM, whereas the PAG/DLP and RVM/DLP combinations are much less
      efficacious. In addition to fixed combinations, inclusion of a low morphine dose
      in one region shifts the analgesic dose-response curves in the others. The marked
      synergy between the PAG and the RVM is sensitive to naloxonazine, implying a role
      for mu 1 receptors. Thus, these studies indicate the presence of intrinsic
      brainstem mu 1 receptor systems with synergistic interactions which can be
      pharmacologically distinguished from the brainstem mu 2 receptors mediating
      supraspinal/spinal synergy.

PMID- 8252390
TI  - Development of chloride transport by the rat choroid plexus, in vitro.
AB  - The uptake and efflux of 36Cl in the lateral ventricle choroid plexus of 1-7-week
      old rats were measured to determine if Cl transport changed with age and if such
      transport responded to inhibitors of CSF secretion and ion transport. The steady
      state (30 min) Cl uptakes were 148 +/- 9.4 nmol.mg-1 dry weight at 1 week and 139
      +/- 7.0 nmol.mg-1 dry weight at 7 weeks, (P > 0.05). The 36Cl efflux was
      significantly slower in 1 and 2 week plexuses compared to more mature tissues (P
      < 0.01) with k (rate coefficient) = 0.029 +/- 0.004 s-1, t1/2 = 24.1 +/- 3.3 s at
      1 week and k = 0.041 +/- 0.003 s-1, t1/2 = 17.4 +/- 1.3 s at 7 weeks. 36Cl efflux
      at 1 week was unaffected by acetazolamide, bumetanide and DIDS (4,4
      diisothiocyanato-stilbene-2,2 disulphonic acid), however, all these drugs
      substantially reduced efflux from 2, 3 and 7 week choroid plexuses. In contrast,
      the Cl conductance blocker, DPC (diphenylamine carboxylate) at 10(-4) M reduced
      36Cl efflux from both 1 and 7 week tissues by 43% and 39%, respectively. These
      findings suggest that some transport systems responsible for movement of Cl out
      of the epithelium are either absent or less functional in the immature rat
      choroid plexus and may account for the relatively low level of CSF secretion in
      younger animals. The unidirectional efflux of 36Cl, J, was calculated for 1 week
      and adult rats, as a function of the choroid plexus volume to surface area ratio
      (V/A).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252391
TI  - Topography of serotonin neurons in the dorsal raphe nucleus that send axon
      collaterals to the rat prefrontal cortex and nucleus accumbens.
AB  - Diverse physiological actions have been reported for 5-hydroxytryptamine (5-HT,
      serotonin) in the medial prefrontal cortex (MPFC) and the nucleus accumbens (Acb)
      suggesting that the 5-HT innervation of these forebrain areas may be derived from
      different populations of neurons. We examined this possibility by mapping the
      distribution of 5-HT-immunoreactive (ir) and non-5-HT-ir neurons containing
      retrograde labeling following injections of different tracers into both these
      target regions. The analysis was focused in the dorsal raphe nucleus (DRN) of the
      midbrain, since 5-HT pathways to the MPFC and Acb primarily originate from this
      area. Volume microinjections of the fluorescent retrograde tracer, Fluoro-Gold
      (FG), were placed into the MPFC and microinjections of cholera toxin B subunit
      coupled to 15 nm gold particles (CT-Au) were placed into the Acb of the same
      animal. Sections through the DRN containing retrogradely labeled neurons were
      further processed for immunofluorescent localization of 5-HT using a rhodamine
      marker. Neurons retrogradely labeled from the Acb were greater in number overall
      than those projecting to the MPFC. In addition, Acb-projecting neurons extended
      into the lateral wings of the DRN, whereas MPFC-projecting neurons were more
      restricted to the midline. Both groups of retrogradely labeled neurons, however,
      were more numerous in the caudal aspect of the dorsal raphe nucleus and were
      scattered amongst 5-HT immunoreactive perikarya. Of 783 +/- 69 CT-Au labeled
      cells, 15% also contained the FG label and 11% contained FG and 5-HT
      immunoreactivity. Of 613 +/- 48 FG labeled cells, 24% also contained the CT-Au
      label and 21% were also immunoreactive to 5-HT. The results suggest a more
      prominent input to the Acb from both 5-HT-ir and non-5-HT-ir neurons in the
      caudal aspect of the DRN and further indicate that while most 5-HT-ir and non-5
      HT-ir neurons project differentially to both forebrain regions, a few cells also
      show collateralization to the MPFC and Acb. Such collateralization of single
      serotonergic neurons to divergent targets may integrate cognitive and motor
      activities in response to pharmacological manipulations of ascending serotonergic
      pathways.

PMID- 8252393
TI  - Progeny of mothers drinking corticosterone during lactation has lower stress
      induced corticosterone secretion and better cognitive performance.
AB  - In order to test the hypothesis that maternal corticosterone influences
      hypothalamus-pituitary-adrenal (HPA) system activity in the adult rat and
      behaviors related to it, we induced a moderate increase in maternal plasma level
      of corticosterone by adding the hormone to the drinking water of the dams (200
      micrograms/ml) from the day after delivery to weaning. Our previous experiments
      have shown that this procedure produces plasma levels of the hormone in the range
      of those following a mild psychic stress (from 4.3 +/- 0.5 to 9.5 +/- 1.8
      micrograms/100 ml in the dams, and from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100
      ml in the pups at 10 days of lactation). Adrenal weights were slightly and
      temporarily decreased by treatment in both mothers and offspring. Only the male
      progeny was investigated in this study. Corticosterone-nursed rats had
      significantly less corticosterone and ACTH in basal conditions and after a 2 min
      restraint stress at 3 months of age, and showed better performances at weaning
      and at 1, 2 and 3 months of life in the Morris water maze. Our results
      demonstrate that a moderate increase in maternal corticosterone during lactation
      influences the activity of HPA axis and improves spatial learning ability of the
      adult offspring.

PMID- 8252392
TI  - The nootropic compound BMY-21502 improves spatial learning ability in brain
      injured rats.
AB  - Although long-lasting cognitive dysfunction often follows clinical traumatic
      brain injury (TBI), few pharmacologic regimens have been developed to treat post
      traumatic cognitive deficits. We have previously shown that, in the rat,
      experimental lateral fluid-percussion (FP) brain injury induces a profound
      impairment in retrograde memory. In the present study, we characterized
      alterations in the ability of rats to learn a novel task following lateral FP
      brain injury and examined the potential modulatory effects of the nootropic
      cognitive enhancer BMY-21502 on post-injury learning. Male Sprague-Dawley rats
      were subjected to lateral (parasagittal) FP brain injury of moderate severity
      (2.4 atm) or sham surgery (no injury). On days 7 and 8 post-injury, animals were
      tested in a Morris water maze for their ability to learn to navigate to a
      submerged, invisible platform using external visual cues. BMY-21502 (10 mg/kg) or
      vehicle was administered 30 min prior to the first trial on both days. A highly
      significant (P < 0.001) impairment in post-injury learning was observed in
      vehicle-treated brain-injured animals compared with vehicle-treated sham animals.
      Injured animals treated with BMY-21502 at one week post-injury showed
      significantly (P < 0.05) improvement in post-injury learning ability compared to
      injured animals treated with vehicle. Paradoxically, in uninjured control animals
      BMY-21502 treatment appeared to worsen learning scores. The results of this study
      indicate that BMY-21502 may be useful for attenuating the dysfunction in learning
      ability that occurs following TBI.

PMID- 8252394
TI  - The effects of in utero ethanol administration on the electrophysiological
      activity of rat nigrostriatal dopaminergic neurons.
AB  - Iontophoresis and single-unit extracellular recording techniques were utilized to
      study the effects of in utero ethanol administration on nigrostriatal
      dopaminergic (NSDA) neurons in adult rats. Pregnant Sprague-Dawley rats consumed
      an ethanol-containing liquid diet providing 0%, 17.5%, or 35% ethanol-derived
      calories (EDC) from gestation day 8 until parturition. A separate group was fed
      standard rat chow as an ad lib, diet control. The dose-response curves of
      intravenously administered apomorphine on the spontaneous activity of NSDA
      neurons were shifted to the right in animals exposed to a liquid diet containing
      17.5% or 35% EDC compared to 0% EDC or ad lib. control groups. The responsiveness
      of NSDA neurons to microiontophoretic application of the D-2 DA receptor agonist,
      quinpirole, was not altered following in utero ethanol exposure. These results
      suggest that in utero ethanol exposure may produce a down-regulation in the
      function of DA receptors distinct from the somatodendritic impulse-regulating D-2
      autoreceptors. The firing pattern of NSDA neurons was also found to be altered
      after in utero ethanol exposure. There was a dissociation between the firing rate
      and burst activity in neurons that displayed burst-firing patterns in animals
      with in utero ethanol exposure. These observations agree with biochemical and
      behavioral studies that in utero ethanol exposure produces a long-lasting effect
      on the development of electrophysiological and pharmacological characteristics of
      midbrain DA systems in adulthood.

PMID- 8252395
TI  - Kainic acid-induced lipid peroxidation: protection with butylated hydroxytoluene
      and U78517F in primary cultures of cerebellar granule cells.
AB  - The generation of free radicals in the progression of kainic acid (KA)-mediated
      neuronal death has been implicated in both in vitro and in vivo studies. In the
      present study, the association between KA-induced neurodegeneration and the
      appearance of lipid peroxidation products was investigated and compared to three
      well characterized free radical generating (FRG) systems: 200 microM ferrous
      ammonium sulfate (FAS), 20 microM copper (Cu2+), and 0.01 U/ml xanthine
      oxidase/2.3 mM purine/2.4 microM transferrin (XO). KA caused a dose-dependent
      increase in conjugated diene and lipid hydroperoxide formation as did the FRG
      systems. The antioxidant, butylated hydroxytoluene (BHT), decreased both FRG
      system- and KA-induced lipid peroxidation by approximately 60-70%. Unlike BHT,
      the potency of the lipid peroxidation inhibitor, U78517F, depended upon the
      system utilized to induce free radical generation. U78517F was most potent in
      attenuating FAS-induced lipid peroxidation (100 nM), followed by KA (1.5 microM),
      and then Cu2+ and XO (> 2 microM). Results were confirmed by measurement of
      cytolysis through the release of lactic dehydrogenase (LDH). These data provide
      further evidence that the generation of free radicals, subsequently leading to
      membrane disruption, is central to the mechanism of KA-elicited neuronal death in
      cultures of cerebellar granule cells.

PMID- 8252396
TI  - Aminooxyacetic acid produces excitotoxic brain injury in neonatal rats.
AB  - Impairment of cellular energy metabolism plays an important role in the
      expression of brain injury resulting from a variety of acute neurologic
      disorders. The role of mitochondrial energy metabolism in excitotoxic perinatal
      brain injury was assessed by studying the toxicity of aminooxyacetic acid (AOAA),
      an inhibitor of mitochondrial malate-aspartate shunt, in postnatal (PND) 7 rats.
      Intrastriatal injection of AOAA produced seizures and dose-dependent excitotoxic
      injury. The neuronal damage was attenuated by pyridoxine suggesting involvement
      of pyridoxal dependent mechanisms. The lesion was selectively blocked by the NMDA
      antagonist MK-801 but not the AMPA antagonist GYKI-52466. Furthermore, AOAA
      potentiated NMDA, but not AMPA or 1S,3R-ACPD, induced brain injury. The data
      suggest that regional impairment of cellular energy metabolism is an important
      determinant of selective vulnerability to excitotoxic injury in perinatal rats.
      Furthermore, the role of impaired energy metabolism is particularly relevant to
      NMDA receptor mediated brain injury.

PMID- 8252397
TI  - Dopaminergic antagonism within the nucleus accumbens or the amygdala produces
      differential effects on intravenous cocaine self-administration under fixed and
      progressive ratio schedules of reinforcement.
AB  - Bilateral intracerebral injections of the D1 receptor antagonist, SCH 23390, were
      administered into the nucleus accumbens (NACC) or amygdala (AMY) immediately
      prior to an i.v. cocaine self-administration session. Injection into both sites
      produced a dose-dependent (0.1-2.0 micrograms/injection) increase in the rate of
      cocaine self-administration under a fixed ratio (FR) schedule of reinforcement
      (1.5 mg/kg/injection). However, injection into the AMY produced a significantly
      greater increase in rate of drug intake than within the NACC. In contrast, under
      a progressive ratio (PR) schedule of cocaine reinforcement the D1 antagonist had
      very little effect within the AMY on break point (BP) but greatly reduced the BP
      following injection into the NACC. A locomotor activity study revealed that
      following systemic injection of cocaine (10 mg/kg i.p.), SCH 23390 (1.0
      microgram/injection site) significantly reduced activity to comparable levels
      following injection into either brain site. This indicates that the dissociation
      of effects between the two neural sites within the cocaine self-administration
      paradigm does not appear to be due to greater locomotor reducing actions of the
      antagonist within the NACC. These results demonstrate that a significant
      contribution is made by AMY dopamine to cocaine reinforcement mechanisms, which
      appears to be different to that of the NACC. Moreover, they suggest that FR and
      PR schedules may measure different aspects of cocaine's CNS action which support
      self-administration behaviour.

PMID- 8252399
TI  - Long-lasting changes in the origin of spontaneous discharges from amygdala
      kindled rats: piriform vs. perirhinal cortex in vitro.
AB  - The origin of spontaneous field potentials in coronal slices of the amygdala
      piriform-perirhinal area (A-P area) from amygdala-kindled and control rats was
      assessed. In Expt. 1, the field potentials initially originated in the perirhinal
      (PRh) cortex of control tissue while they originated in the piriform (Pir) cortex
      of amygdala-kindled tissue. In Expt. 2, this kindling-based change was observed
      in the A-P area ipsilateral but not contralateral to the kindled amygdala. In
      both experiments, subsequent exposure to perfusion medium containing 0 Mg2+
      resulted in the genesis of strong discharges in both control and kindled tissues.
      After 2-3 h of such treatment, the origin of spontaneous discharges in control
      tissue changed from the PRh to the Pir area and persisted in a reduced form
      during reperfusion with medium containing Mg2+. This change in origin of the
      discharges in control tissue appeared similar to that seen in previously kindled
      tissue. In Expt. 3, during exposure to 0 Mg2+, the response of the basolateral
      amygdala (BLA) was compared with the Pir and PRh areas. Independent of the PRh
      discharge, the BLA discharge closely followed the Pir discharge both in time and
      morphology. These lasting changes in the ipsilateral A-P area in vitro must be
      related in vivo to the change which allows the kindled A-P area to participate in
      the triggering of generalized limbic-kindled convulsions.

PMID- 8252398
TI  - Sexual stimulation activates c-fos within estrogen-concentrating regions of the
      female rat forebrain.
AB  - Regions of the brain that concentrate estrogen and progesterone are thought to
      regulate female sexual behavior by altering gene expression and neural
      sensitivity to afferent stimulation. We used immunocytochemistry and in situ
      hybridization to examine c-fos gene expression within estrogen-concentrating
      regions of the forebrain following various types of sexual stimulation with or
      without hormone treatment. Ovariectomized rats received injections of estradiol
      benzoate 48 h and progesterone 4 h before testing. Control rats that had been
      ovariectomized at least 5 months before testing did not receive hormone
      treatment. Rats were then either placed into bilevel testing chambers with
      sexually vigorous males, received manual stimulation of the flanks, received
      vaginocervical stimulation with a glass rod, or were left in their home cages.
      Copulation with intromission and ejaculation in hormone-treated rats, or
      stimulation of the vaginal cervix in both hormone-treated and control rats,
      produced a dramatic induction of c-fos mRNA and Fos-like immunoreactivity in
      estrogen-concentrating regions, such as the lateral septum, medial preoptic area,
      bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus,
      ventromedial hypothalamus, lateral habenula, and medial amygdala, in addition to
      regions that do not readily concentrate estrogen, such as the neocortex,
      thalamus, and striatum. Mechanical stimulation of the flanks produced a smaller
      induction of Fos in these rats, whereas hormone treatment alone had no effect.
      These data demonstrate that afferent sensory stimulation, but not estrogen or
      progesterone, regulates c-fos gene expression within different estrogen
      concentrating and non-concentrating regions of the female rat forebrain.

PMID- 8252400
TI  - Facilitatory modulation of mesolimbic dopamine neuronal activity by a mu-opioid
      agonist and nicotine as examined with in vivo microdialysis.
AB  - Administration of either Tyr-D-Ala-Gly-MePhe-Gly(ol) (DAGO), a mu-opioid agonist,
      or nicotine into the VTA (A10) caused an increase in both dopamine (DA) and its
      metabolite levels in both the A10 region and DA nerve terminals in the nucleus
      accumbens of rats when assessed with dual probe brain dialysis. These findings
      show that DAGO and nicotine increase both axonal- and somatodendritic-DA release,
      as well as metabolic activity in mesolimbic DA neurons, possibly by inducing an
      increase in neuronal impulse flow.

PMID- 8252401
TI  - The amygdaloid complex, corticotropin releasing factor and stress-induced gastric
      ulcerogenesis in rats.
AB  - The amygdaloid complex and corticotropin releasing factor (CRF) are both
      important in stress reactions and we thus evaluated the effects of intra
      amygdalar CRF on stress ulceration in rats. Bilateral micro-applications of CRF
      (0.05, 0.5 or 5.0 micrograms) into the central amygdala (CEA) attenuated cold
      restraint-induced gastric mucosal lesions in a dose-related manner. Similar
      gastric cytoprotective effects were seen with intra-CEA noradrenaline (NA; 3.0
      micrograms), whereas the NA neurotoxin, DSP-4 (25 micrograms), or the beta
      adrenoceptor antagonist, propranolol (1 microgram), aggravated stress ulcer
      pathology. Intra-CEA pretreatment with DSP-4 or propranolol clearly reversed the
      ulceroprotective effects of CRF during stress. These results indicate that the
      CEA is a neural substrate for CRF effects, and CRF-NA interactions in this limbic
      area are crucial for the regulation of stress ulcerogenesis.

PMID- 8252402
TI  - Norepinephrine turnover in the goldfish brain is modulated by sex steroids and
      GABA.
AB  - It is known that norepinephrine (NE) is important in the neuroendocrine control
      of pituitary gonadotropin II (GTH-II) and growth hormone (GH) release but very
      little is known about the factors regulating NE neurons in the goldfish brain.
      Female gonad-intact goldfish were implanted intraperitoneally (100 micrograms/g)
      with testosterone (T) or estradiol (E2) to elevate serum steroid levels. High
      performance liquid chromatography measurements showed that steroid implantation
      had no effect on NE content in the telencephalon, including preoptic area (TEL
      POA), or the hypothalamus (HYP). The turnover rate of NE was estimated from the
      rate of depletion of NE content from tissues following inhibition of tyrosine
      hydroxylase by alpha-methyl-p-tyrosine (240 micrograms/g). The present study
      demonstrates that E2 can decrease NE turnover rates in TEL-POA and HYP of
      sexually regressed goldfish (August). The results in recrudescent fish
      (November), however, indicate a more complex interaction of E2 with NE neurons
      since E2 increased NE turnover in TEL-POA and HYP in these animals. Testosterone
      (T) has less prominent effects on NE turnover rates in TEL-POA and HYP; the only
      significant effect of T-implantation was a small reduction of NE turnover in the
      TEL-POA of sexually recrudescent fish. Elevation of endogenous brain GABA
      concentrations by injection of the GABA transaminase inhibitor, gamma-vinyl-GABA
      (300 micrograms/g), significantly reduced NE turnover in TEL-POA. These data
      demonstrate that goldfish NE neurons in the TEL-POA are sensitive to regulation
      by changes in circulating sex steroids and by increases in brain GABA.

PMID- 8252403
TI  - Induction of tumor necrosis factor-alpha mRNA in the brain after peripheral
      endotoxin treatment: comparison with interleukin-1 family and interleukin-6.
AB  - The constitutive expression of tumor necrosis factor-alpha (TNF alpha) mRNA and
      its induction (60 min later) by peripheral injection of Escherichia coli
      lipopolysaccharide (2 mg/kg i.p.) was demonstrated by polymerase chain reaction
      (PCR), in the pituitary and hypothalamus but not in the striatum or hippocampus
      of the rat. The pattern of TNF alpha mRNA induction is different from that
      observed for mRNAs of IL-1 alpha and IL-1 beta, IL-1ra and IL-6 respectively.
      This demonstration of the induction of TNF alpha in the brain may contribute to
      our understanding of the central effects of TNF alpha in fever and anorexia.

PMID- 8252404
TI  - Effects of chronic nicotine and pilocarpine administration on neocortical
      neuronal density and [3H]GABA uptake in nucleus basalis lesioned rats.
AB  - We investigated the possible long-term neuroprotective roles of (-)nicotine and
      muscarinic agonist, pilocarpine, in the neocortices of rats receiving bilateral
      nucleus basalis lesions. Ibotenic acid-lesioned animals eventually displayed a 15
      20% reduction in the density of neocortical Nissl staining neurons in layers II,
      III and VI, as well as a 27% loss in high-affinity GABA uptake 8 months post
      lesioning. Deficits were not observed at earlier intervals. (-)Nicotine (0.2
      mg/kg, i.p.) or (-)nicotine plus pilocarpine (1 mg/kg, i.p.) attenuated these
      losses when administered once daily to rats from 5-8 months post-lesioning.
      Pilocarpine alone had no protective effect on neuronal density or GABA uptake.
      These results suggest that nicotine receptor activation may counteract
      neocortical neuronal loss/atrophy following loss of ascending basal forebrain
      neurons.

PMID- 8252405
TI  - Fetal hippocampal transplants reduce aberrant mossy fiber sprouting after CA3
      pyramidal cell damage.
AB  - The CA3 pyramidal cells receive mossy fibers from the dentate granule cells, and
      the damage to CA3 pyramidal cells induces aberrant mossy fiber sprouting near the
      site of normal targets. Fetal CA1 and CA3 subregions were separately transplanted
      into the host CA3 subfield, where CA3 pyramidal neurons were previously damaged
      with kainic acid. In vitro [3H]inositol 1,4,5-trisphosphate (IP3) receptor
      autoradiography was used to analyze the purity of CA1 neurons. CA1 transplants
      had high IP3 receptor density compatible with adult CA1 subfield, while CA3
      transplants had trace IP3 receptors. Animals with successful graft-host
      connections exhibited no aberrant mossy fiber sprouting, and mossy fibers invaded
      into the fetal CA3 grafts. However, animals without direct host mossy fibers
      grafts connection showed aberrant mossy fiber sprouting in the CA3 subfield.
      These observations demonstrate that aberrant mossy fiber sprouting was suppressed
      by molecular cues presented on the grafted neurons and that [3H]IP3 receptor
      autoradiography provides an excellent marker for the identification of the CA1
      pyramidal cells in grafts.

PMID- 8252406
TI  - Glutaminase-like immunoreactivity in rat spinomesencephalic tract cells.
AB  - Retrograde transport of the fluorescent tracer Fluorogold was used in combination
      with immunohistochemical staining for the enzyme glutaminase to identify putative
      glutamatergic neurons belonging to the rat spinomesencephalic tract. Glutaminase
      like staining in spinal projection neurons suggests that the relay of nociceptive
      information from the spinal cord to midbrain may involve the excitatory amino
      acid glutamate.

PMID- 8252407
TI  - Absence of androgen receptors in LHRH immunoreactive neurons.
AB  - Androgen has a negative feedback effect upon reproductive functions. Studies have
      suggested that this effect is mediated partially at the hypothalamic level.
      However, it is not clear whether the action is direct or indirect on LHRH
      neurons. In the present study, double immunocytochemistry was used to localize
      LHRH and androgen receptors. Out of 5892 LHRH immunoreactive neurons, no double
      labelled neurons were observed. We conclude that the feedback effect of androgen
      on the central nervous system is mediated by indirect pathway(s).

PMID- 8252408
TI  - Distribution of calretinin mRNA in rat spinal cord and dorsal root ganglia: a
      study using non-radioactive in situ hybridization histochemistry.
AB  - Using non-radioactive in situ hybridization calretinin mRNA was detected in
      numerous small neurons within lamina II and IV of the dorsal horn. Many labelled
      cells are distributed over the whole ventral horn; however, no motoneurons
      contained the mRNA. In dorsal root ganglia 4.9 +/- 1.7% (mean +/- S.D., n = 5
      animals) of the primary afferent neurons contained calretinin mRNA. Labelled
      cells were of intermediate and large size with diameters ranging from 36 to 68
      microns indicating that calretinin is synthesized in neurons with myelinated
      afferent fibers and presumably a corpuscular ending.

PMID- 8252409
TI  - Co-occurrence of gamma-aminobutyric acid, parvalbumin and the neurotensin-related
      neuropeptide LANT6 in pallidal, nigral and striatal neurons in pigeons and
      monkeys.
AB  - Immunohistochemical double-labeling techniques were used to examine the co
      localization of the neurotransmitter gamma-aminobutyric acid (GABA), the calcium
      binding protein parvalbumin and the neurotensin-related hexapeptide LANT6 in
      neurons of the striatum and its target areas in pigeons and monkeys. The studies
      revealed the existence of a population of striatal interneurons apparently
      containing all three of these substances in both monkeys and pigeons. The results
      also revealed that GABA and LANT6 were co-localized in numerous pallidal and
      nigral reticulata neurons that also contained parvalbumin in both species.
      Examination of diverse other cell groups in avian forebrain and midbrain revealed
      that parvalbumin and LANT6 were typically co-localized to GABAergic neurons. In
      light of the presence of pallidal, reticulata and striatal neurons containing
      these three substances in two widely divergent amniote groups such as pigeons and
      monkeys, it seems likely that: (1) comparable neuronal populations are present in
      other avian and mammalian species; and (2) these neuronal populations play a
      fundamental role in basal ganglia functions that requires these three substances.

PMID- 8252410
TI  - Modulation by divalent cations of the current generated by vasopressin in facial
      motoneurons.
AB  - Vasopressin generates a voltage-gated, sodium-dependent current in facial
      motoneurons in brainstem slices. Reducing the extracellular calcium concentration
      from 2 to 0.01 mM caused a 30 to 120% increase in the amplitude of this current.
      Lowering extracellular magnesium also enhanced it, but less efficiently. In the
      physiological solution, the response of facial neurons to vasopressin is thus
      partially blocked. Increasing extracellular calcium was without effect. Current
      voltage curves indicate that the vasopressin current reversed at around 0 mV and
      suggest that the low-calcium-induced potentiation was due to an attenuation of
      the region of negative slope conductance.

PMID- 8252411
TI  - Vasoactive intestinal peptide: a growth promoter in neuroblastoma cells.
AB  - Vasoactive intestinal peptide (VIP) is a neuromodulator, growth regulator and
      secretagogue for neuronal survival factors. Moreover, VIP has been suggested to
      be a mitogenic factor for embryonic neurons in the sympathetic nervous system. We
      now show that VIP had mitogenic activity in a human neuroblastoma cell line
      (NMB), as measured by cell number and thymidine incorporation. This mitogenic
      activity was dose dependent and was decreased with culture maturation. Northern
      blot analysis revealed VIP mRNA transcripts in this cell line suggesting an
      autocrine role for VIP in neurogenesis.

PMID- 8252412
TI  - Lesions of the suprachiasmatic nucleus do not disturb sexual orientation of the
      adult male rat.
AB  - An enlarged suprachiasmatic nucleus (SCN) has been found earlier in a group of
      homosexual men, as compared to heterosexual controls. In order to assess a
      possible relationship between the SCN and sexual orientation, the present study
      was undertaken to investigate whether the rat SCN might play a role with respect
      to the expression of sexual orientation. Sexual orientation was measured in
      partner preference tests as the percentage of time spent in the vicinity of
      sexually active male and female incentives, that were separated from the
      experimental animal by a wire mesh. The results show that established patterns of
      sexual orientation towards female incentives by the adult male rat are not
      influenced by SCN-lesions. Disturbances in circadian rhythmicity of activity in
      SCN-lesioned animals did not affect this conclusion.

PMID- 8252413
TI  - Organization and quantitative analysis of kainate receptor subunit GluR5-7
      immunoreactivity in monkey hippocampus.
AB  - A monoclonal antibody specific for GluR5-7 (mAb-4F5) has been used to
      characterize the distribution of kainate class glutamate receptor subunits in
      monkey hippocampus. Immunolabeled neurons were present in all subfields of the
      hippocampus as well as the dentate gyrus and subiculum. Quantitative
      immunofluorescence analysis by confocal microscopy demonstrated differential
      levels of immunoreactivity such that the highest intensities were in neurons
      within CA1 and subiculum as compared with those within CA3 or dentate gyrus. The
      regional differences in levels of subunit immunoreactivity correlate with the
      relative vulnerability of hippocampal neurons in several neurodegenerative
      disorders.

PMID- 8252414
TI  - Loss of serotonin uptake sites and immunoreactivity in rat cortex after
      dexfenfluramine occur without parallel glial cell reactions.
AB  - The frontal cortices of rats which received either D,L- or D-fenfluramine (DFEN)
      for 4 days were examined 18 h to 2 weeks following treatment for changes in
      synaptosomal uptake of serotonin (5HT), paroxetine binding, 5HT-immunoreactivity
      (5HT-IR), and both astrocytic (GFAP) and microglial markers. Additional rats
      received intracerebroventricular injections of the neurotoxin 5,7
      dihydroxytryptamine (DHT). Consistent with previous reports, D,L- and DFEN
      produced dose-dependent losses of both 5HT uptake and paroxetine binding, and
      loss of 5HT-IR which coincided with an abnormal or 'swollen' appearance of
      immunoreactive axon processes. Recovery of these serotonergic indices was
      greatest following the lowest doses of DFEN, but was absent after 5,7-DHT
      treatment. No evidence for an increase in GFAP synthesis or microglial activation
      was observed in frontal cortices of rats treated with either DFEN or 5,7-DHT. We
      conclude that the presence of swollen 5HT-IR axons in the cortices of both the
      5,7-DHT and DFEN groups is insufficient to trigger the glial responses often
      associated with neuronal degeneration. Thus, it remains to be determined if
      swollen 5HT-IR axons are a prelude to neurodegeneration, or whether they
      represent reversible changes in axonal immunochemistry associated with decreases
      in 5HT levels. The implications of the data for the clinical safety of DFEN are
      briefly discussed.

PMID- 8252415
TI  - Antagonism of estrogenic effects on feeding behavior by central implants of
      anisomycin.
AB  - The following experiment determined whether the estrogenic suppression of food
      intake is dependent upon changes in protein synthesis within neurons of the
      paraventricular nucleus of the hypothalamus (PVN). Ovariectomized rats were
      treated centrally with anisomycin-filled or empty (control) cannulae in the PVN.
      Females were injected with either 2.0 micrograms of estradiol benzoate (EB) or
      the oil vehicle and the inner cannulae were removed 2 h later. EB injections
      significantly lowered food and water intake in the central control group but not
      in animals given PVN implants of anisomycin. Body weight gain decreased for all
      females. EB induced comparable levels of female sexual behavior in both groups,
      demonstrating that anisomycin implants did not affect the ability of estradiol to
      stimulate lordosis. These findings indicate that the effects of estradiol on food
      intake require the activation of protein synthesis in estrogen-sensitive PVN
      neurons.

PMID- 8252416
TI  - Role of IL-1 alpha in central nervous system immunomodulation of glucoregulation.
AB  - Hyperglycemia is a hallmark of the stress response, and has been largely
      attributed to elevated plasma levels of catabolic hormones. Recently, various
      cytokines have been shown to be endogenously produced within the brain and may
      represent an important component of the central regulation of this metabolic
      response. Therefore, the aim of the present study was to determine whether the
      intracerebroventricular (i.c.v.) injection of one such peptide, interleukin (IL)
      1, can produce hormonal and metabolic alterations comparable to those observed
      under stress conditions. An i.c.v. cannula and vascular catheters were placed in
      rats prior to the experiment. Whole body glucose flux was assessed in overnight
      fasted conscious unrestrained rats using [3-3H]glucose. A mild hyperglycemia was
      elicited 20 min after the i.c.v. injection of IL-1 alpha (human recombinant, 100
      ng) that was not detected in control rats. Glucose levels gradually increased and
      were 26% higher than control values during the last hour of the 3 h experimental
      period. The hyperglycemia resulted from a 44% increase in the rate of hepatic
      glucose output (HGO), which preceded a proportional rise in peripheral glucose
      utilization. No increase in metabolic clearance rate was observed, suggesting
      that the increased glucose uptake was the result of mass action. The increased
      glucose flux was associated with a transient hyperinsulinemia (+95%), and
      sustained elevations in the arterial concentrations of glucagon (56%) and
      corticosterone (175%). In contrast, glucose flux was not altered by intravenous
      administration of the same dose of IL-1 alpha, or i.c.v. injection of IL-1 beta,
      or heat-inactivated IL-1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252417
TI  - Intracerebroventricular injection of interleukin-1 beta induces hyperalgesia in
      rats.
AB  - To determine whether interleukin-1 beta (IL-1 beta) in the brain may modulate
      nociception, recombinant human IL-1 beta (rhIL-1 beta) (1 pg/kg to 1
      microgram/kg) was microinjected into the lateral cerebral ventricle of rats and
      the latency before initiating the licking of their hindpaws after being placed on
      a hot plate (50.0 +/- 0.1 degrees C) was measured. A significant reduction of the
      paw-lick latency was observed after injections of nonpyrogenic doses (10 pg/kg to
      1 ng/kg) of rhIL-1 beta, showing a maximal response at a dose of 100 pg/kg which
      began to appear 5 min after injection, reached a peak within 30 min and then
      gradually subsided. An increase in the amount of rhIL-1 beta to > 1 ng/kg (up to
      1 microgram/kg) had no effect on the nociceptive threshold. The rhIL-1 beta
      induced hyperalgesia was completely abolished by pretreatment with an IL-1
      receptor antagonist (IL-1ra) or Na salicylate. Similar pretreatment with alpha
      melanocyte-stimulating hormone (alpha-MSH) also inhibited the rhIL-1 beta-induced
      hyperalgesia. However, pretreatment with alpha-helical corticotropin-releasing
      factor (CRF)9-41 failed to affect it. The results suggest that IL-1 beta in the
      brain produces hyperalgesia by its receptor-mediated and prostaglandin-dependent
      action which is sensitive to alpha-MSH. The hyperalgesic action of central IL-1
      does not appear to depend on the CRF system.

PMID- 8252418
TI  - Protein kinase C isozymes that mediate enhancement of neurite outgrowth by
      ethanol and phorbol esters in PC12 cells.
AB  - Using PC12 cells to study ethanol's effects on growth of neural processes, we
      found that ethanol enhances NGF- and basic FGF-induced neurite outgrowth. Chronic
      ethanol exposure selectively up-regulates delta and epsilon protein kinase C
      (PKC) and increases PKC-mediated phosphorylation in PC12 cells. Since PKC
      regulates differentiation, we investigated the role of PKC in enhancement of
      neurite outgrowth by ethanol. Like ethanol, 0.3-10 nM phorbol 12-myristate, 13
      acetate (PMA) increased NGF-induced neurite outgrowth. However, higher
      concentrations did not, and immunoblot analysis demonstrated that 100 nM PMA
      markedly depleted cells of beta, delta and epsilon PKC. PMA (100 nM) also down
      regulated beta, delta and epsilon PKC in ethanol-treated cells and completely
      prevented enhancement of neurite outgrowth by ethanol. In contrast, the cAMP
      analogue 8-bromoadenosine cAMP did not completely mimic the effects of ethanol on
      neurite outgrowth, and ethanol was able to enhance neurite formation in mutant
      PC12 cells deficient in protein kinase A (PKA). These findings implicate beta,
      delta or epsilon PKC, but not PKA, in the neurite-promoting effects of ethanol
      and PMA. Since chronic ethanol exposure up-regulates delta and epsilon, but not
      beta PKC, these findings suggest that delta or epsilon PKC regulate neurite
      outgrowth.

PMID- 8252420
TI  - The Canadian Radiological Foundation.

PMID- 8252419
TI  - Concussive brain injury is associated with a prolonged accumulation of calcium: a
      45Ca autoradiographic study.
AB  - In order to determine the extent and duration of calcium (Ca2+) flux following a
      lateral fluid percussion brain injury in the rat, 45Ca autoradiography was used
      to study animals immediately, 6, 24 and 96 h after the insult. In addition, cell
      suspension studies were conducted to determine the extent of cellular flux of
      45Ca. Optical density and/or scintillation counting was utilized to provide a
      relative measure of 45Ca accumulation within 20 different structures. The results
      indicated that in animals who exhibited no gross morphological damage, 45Ca
      accumulation following injury was exhibited primarily within the ipsilateral
      cerebral cortex, dorsal hippocampus and striatum. This accumulation continued for
      several days returning to control levels by the 4th day after injury. In animals
      who sustained morphological damage, the contusion site exhibited a marked
      accumulation of 45Ca which did not resolve spontaneously over the course of 4
      days. We conclude from this work that Ca2+ flux is a major component of this
      experimental model of traumatic injury. Furthermore, that depending on the extent
      of cell damage, the accumulation of Ca2+ is regionally different. Finally, that
      even in an injury which by itself does not produce gross morphological tissue
      damage, accumulation of Ca2+ can continue for at least 48 h.

PMID- 8252421
TI  - Acute abdomen: plain film utilization and analysis.
AB  - Abdominal radiographs are commonly requested indiscriminately for patients with
      abdominal pain, but the results of many such examinations are negative or non
      specific. In today's era of high-technology studies, such as ultrasonography,
      computed tomography and magnetic resonance imaging, plain abdominal radiography
      is still appropriate in some situations, and the interpretation of abdominal
      plain films remains an essential and challenging component of most radiology
      practices. This article reviews a number of issues regarding the use of plain
      radiography: the common causes of abdominal pain in patients presenting to a
      typical emergency department; the appropriate indications for this type of
      examination so that the number of unnecessary examinations is minimized and the
      diagnostic yield thereby maximized; and the appropriate views to be obtained, the
      rationale for their use and a proposed format for standardized viewing of
      abdominal plain films. The article concludes with a practical review of some
      commonly misunderstood points regarding the bowel gas pattern and ascites.

PMID- 8252422
TI  - Transrectal drainage of deep pelvic collections under fluoroscopic guidance.
AB  - Although transrectal drainage of pelvic fluid collections, guided by fluoroscopy,
      computed tomography (CT) and ultrasonography (US), has been reported, the
      cumulative experience is small. The authors describe a technique for
      fluoroscopically guided transrectal drainage and present the results obtained for
      13 patients. Each patient underwent diagnostic CT and then fluoroscopically
      guided drainage. A barium enema tube assembly, consisting of an enema tube, a
      Lunderquist PTC (percutaneous transhepatic cholangiogram) needle and a small
      portion of a red rubber catheter, was used to facilitate insertion of the
      drainage catheter. The procedure was defined as successful if complete clearance
      occurred after drainage, as temporizing if partial drainage was achieved and
      clinical improvement occurred, and as failed if the collection showed no response
      to drainage. Twelve of the patients had abscesses, 9 of which were successfully
      treated by drainage alone; one drainage was temporizing and two failed. The
      collection in the last patient represented a hematoma, which did not respond to
      drainage. The authors conclude that the technique they describe is suitable for
      draining moderate to large pelvic abscesses. The procedure is safe and can easily
      be performed in both male and female patients.

PMID- 8252423
TI  - Doppler ultrasonography after renal transplantation: value of reversed diastolic
      flow in diagnosing renal vein obstruction.
AB  - The observation of reversed diastolic flow during Doppler ultrasonography (US) of
      renal transplants has been described as sensitive but not specific in the
      diagnosis of renal vein thrombosis. To determine the diagnostic accuracy of
      reversed diastolic flow for renal vein obstruction in patients who underwent
      renal transplantation at a tertiary-care teaching hospital over a 3-year period,
      the authors identified all patients in whom reversed diastolic flow was observed
      during Doppler US (17 patients) and those in whom complete renal vein obstruction
      occurred, necessitating nephrectomy (16 patients). Three types of reversed
      diastolic flow were found; the wave-forms of two of these had a large reversed
      component. One of these two types was present in nine of the patients in whom
      complete venous obstruction occurred. The sensitivity, specificity and positive
      predictive value of reversed diastolic flow were 82%, 99% and 75% respectively.
      The authors conclude that a US finding of reversed diastolic flow with a large
      reversed component is a sensitive and specific sign of renal vein obstruction,
      usually renal vein thrombosis.

PMID- 8252424
TI  - Antenatal diagnosis of congenital diaphragmatic hernia.
AB  - The mortality rate in cases of antenatally diagnosed congenital diaphragmatic
      hernia (CDH) remains high: 80% to 100% mortality was reported in early series and
      73% in a more recent series. In addition, the early reports described 100%
      mortality for cases diagnosed before 24 weeks gestational age. To determine the
      mortality rate in patients at their institution (a specialized tertiary-care
      hospital), the authors reviewed 11 cases of CDH diagnosed from 1987 to 1990, for
      all of which antenatal ultrasonography (US) had been performed at the hospital.
      Overall, 7 of the 11 patients survived. In seven of the cases the condition had
      been diagnosed antenatally. Of these patients, four survived, including two of
      the three in whom the diagnosis had been made before 21 weeks gestational age.
      All four false-negative cases involved a right-side hernia, and in three of these
      the prenatal US examinations had been performed before 16 weeks gestational age.
      Three of these four patients survived. This study suggests that the prognosis in
      antenatally diagnosed CDH is improving and confirms that this condition is not
      uniformly fatal in cases diagnosed before 24 weeks gestational age.

PMID- 8252425
TI  - Workload and sources of remuneration for radiologists at a tertiary-care teaching
      hospital in Ontario.
AB  - Detailed information about workload and sources of remuneration for radiologists
      at a large tertiary-care teaching hospital was reviewed for the calendar year
      1991 as part of an assessment of medical professional resources. Radiologists at
      this facility worked an average of about 50 hours per week. When the intensity of
      the cases was taken into consideration, there was only a small variation among
      individual radiologists in terms of workload and income earned for the group.
      Ninety-three percent of the radiologists' remuneration came as payment for
      clinical patient care. The radiologists were poorly remunerated for the time they
      spent teaching, conducting research and performing administrative duties, but
      this low level of remuneration was partially compensated by the activity of
      senior residents, who did some work without supervision.

PMID- 8252426
TI  - Occult severe hyperflexion sprain of the lower cervical spine.
AB  - Three patients with occult severe hyperflexion sprain of the lower cervical spine
      are described. Because the spine radiographs obtained at the time of trauma were
      physiologically normal, the complete instability was initially overlooked. The
      authors recommend an algorithm for adequate diagnosis of this condition.
      Posterior cervical fusion is the treatment of choice.

PMID- 8252427
TI  - Transient global amnesia after cerebral angiography with iohexol.
AB  - Transient global amnesia is an unusual neurologic phenomenon that occasionally
      occurs after angiography, usually of the cerebral vessels. It represents a benign
      event, and normal function is ultimately restored, but the amnesia may be
      frightening for both the patient and the physician until its nature is
      recognized. The authors describe two cases of transient global amnesia occurring
      after cerebral angiography with iohexol, outline the criteria for the diagnosis
      and discuss the proposed mechanism of the phenomenon.

PMID- 8252428
TI  - Cystic intracranial schwannoma.
AB  - The development of cystic components in intracranial schwannoma is not rare but
      has not been emphasized in any previous series or reviews. Cystic areas usually
      develop from coalescence of mucinous or microcystic areas in Antoni B tissue of
      the schwannoma. Hemorrhagic degeneration or necrosis due to the characteristic
      vascular abnormalities of these lesions may cause the formation of tiny cysts but
      not large ones. The formation of an associated arachnoid cyst and, rarely, the
      formation of cysts in glandular or pseudoglandular elements have also been
      reported. Awareness of the potential for partially or largely cystic schwannoma
      of the acoustic or trigeminal nerve is important for both the differential
      diagnosis and surgical planning. Surgically proven large cysts (occupying more
      than 50% of tumour volume) were detected preoperatively by computed tomography
      (CT) in 7 of the 35 cases of acoustic nerve schwannoma and both cases of
      trigeminal nerve schwannoma managed surgically at the authors' institution
      between 1980 and 1990. In a review of the literature the authors found
      descriptions of low-attenuation regions in CT scans for an average of 13% of
      acoustic and 29% of trigeminal nerve sheath tumours. Magnetic resonance imaging,
      ideally performed after intravenous administration of contrast material, also
      plays an important role in the detection and delineation of these tumour cysts.

PMID- 8252429
TI  - Extension of a cerebellar cystic astrocytoma into the cervical canal,
      demonstrated by magnetic resonance imaging.
AB  - One characteristic feature of ependymomas of the fourth ventricle is a tendency
      to extend through the foramina, specifically the foramina of Luschka and
      Magendie, the foramen magnum and the aqueduct of Sylvius. The authors report a
      case of pilocytic astrocytoma of the cerebellum that mimicked such extension into
      the upper cervical canal. This finding was revealed by magnetic resonance imaging
      and confirmed at surgery.

PMID- 8252430
TI  - Ultrasonographic appearance of uterine lipoleiomyoma.
AB  - A uterine lipoleiomyoma in a 43-year-old woman is described and pathological
      correlation of the diagnosis provided. The lesion appeared in transabdominal
      ultrasonography (US) scans as highly echogenic areas producing the marked
      attenuation typical of a lipomatous tumour of the uterus. In this case US alone
      was specific enough to allow tissue characterization and establish an accurate
      preoperative diagnosis.

PMID- 8252431
TI  - Magnetic resonance imaging of a giant nonfunctioning retroperitoneal
      paraganglioma.
AB  - The authors describe the magnetic resonance imaging (MRI), computed tomographic,
      ultrasonographic and angiographic appearance of a giant nonfunctioning
      retroperitoneal paraganglioma. To their knowledge, the MRI appearance of a
      nonfunctioning paraganglioma has not been previously described. The MRI
      characteristics of the nonfunctioning tumour were similar to those of a
      functioning paraganglioma and included hyperintensity in T2-weighted images and
      intense enhancement after intravenous administration of contrast agent.

PMID- 8252432
TI  - Hepatic pseudomass observed with computed tomography after direct injection of
      contrast agent into the portal vein.
AB  - Hepatic pseudomasses have been described on both non-contrast and contrast
      enhanced computed tomography (CT) scans, as well as on scans obtained by CT
      arteriography and CT-portography. The authors describe a hepatic pseudomass that
      appeared in CT scans after direct injection of contrast material into the portal
      vein through an indwelling catheter.

PMID- 8252433
TI  - Hepatic mass with intra-abdominal hemorrhage.

PMID- 8252434
TI  - More early references to air reduction of intussusception.

PMID- 8252435
TI  - Residents' corner. Answer to case of the month #22. Diagnosis. Celiac disease
      complicated by adenocarcinoma.

PMID- 8252436
TI  - Overview and outcomes.
AB  - A great deal of progress has been made regarding improved prehospital transport,
      the quality of trauma care, and injury prevention research. The analysis of the
      four determinants of outcome in the trauma victim allowed for the discovery of
      subgroups who may benefit from a change in triage, resuscitation, or management.
      Our recent investigation into the effect of host factors on mortality resulted in
      the discovery that pre-existing illness predicts outcome independent of other
      determinants, including age and ISS. This article serves as an introduction to
      the effect of PED on trauma victims, including prevalence of specific PED, as
      well as disease-specific treatment considerations. The bottom line in care of any
      trauma victim is that all deviations from normal must be noted, but they should
      be evaluated properly with respect to the acute injuries. It is the authors' hope
      that this overview will guide the intensivist in focusing on the treatment of
      acute injuries without losing sight of the importance of both recognizing and
      managing chronic illnesses so their detrimental effect on patient outcome can be
      minimalized. A large multicenter investigation is needed to see whether these
      recommendations will, in fact, positively impact on trauma victim outcome.

PMID- 8252437
TI  - Resuscitation and initial management.
AB  - This article deals with the initial evaluation and management of the trauma
      victim, from hospital admission to stabilization. The emphasis is on the multiple
      injury patient who requires lifesaving intervention within the first hour of
      admission, with special emphasis on trauma patients with pre-existing disease.

PMID- 8252438
TI  - Anesthetic considerations.
AB  - Proper anesthetic care begins with a thorough preoperative assessment. This can
      rarely be performed in the acute trauma victim. Specific disease states in the
      cardiovascular, endocrine, hematologic, and respiratory systems are considered
      here. Substance abuse is also discussed. A better understanding of the
      interactions between pre-existing disease and traumatic injury should result.

PMID- 8252439
TI  - Pharmacology, monitoring, and nutritional support.
AB  - Three areas of particular importance in dealing with critical complications of
      trauma are pharmacology, monitoring, and nutritional support. This article deals
      with each of these from the perspective of the doctor or nurse at the bedside.
      This survey stands as a sampler and guidebook to these subjects as they pertain
      to the critically ill multiple trauma patient.

PMID- 8252440
TI  - Hemodynamic resuscitation.
AB  - Hemodynamic resuscitation for hemorrhagic shock should be directed toward
      optimizing oxygen delivery to the tissues. A combination of volume restoration
      and inotropic support usually is needed. This article identifies the basis and
      strategies necessary for accomplishing these goals.

PMID- 8252441
TI  - Neurologic trauma concerns.
AB  - Patients with underlying medical illnesses or conditions will comprise a
      progressively larger proportion of head-injury patients given the aging of the
      general population and improved survival in serious illnesses. Age and underlying
      illness can influence the presentation, management, and outcome of head injuries
      by increasing the frequency, severity, and complications from head injury. This
      article examines the conditions that are most often associated with head injury.

PMID- 8252442
TI  - Human immunodeficiency virus and infectious considerations.
AB  - In summary, HIV is a retrovirus with devastating consequences for those infected.
      Primary modes of transmission are through sexual contact and parenteral exposure
      to infected blood and body fluids. Prevalence of the virus among trauma patients,
      risk of exposure, and infection of health care workers are variable and to a
      large extent not known. Existing HIV infection and AIDS have both direct and
      indirect effects on care and outcome of trauma patients. Caring for these
      patients presents many challenges. Manifestations and complications of each
      condition may mask, mimic, or compound the other. Optimal care and outcome depend
      on knowledge of both diseases, and the specific nuances of their management. As
      with all trauma patients, a team approach coordinated by an identified team
      leader is indicated. Finally, to protect both the patient and the care giver,
      policies that effectively reduce exposure must be formulated, promulgated, and
      practiced.

PMID- 8252443
TI  - Economic considerations.
AB  - The costs to society of trauma care are huge. Multiple-injury patients in
      critical care units consume a vast percentage of the direct medical costs. This
      article examines the role that pre-existing diseases have on the length of stay
      in the critical care unit and the costs associated with this care.

PMID- 8252444
TI  - Ethical considerations.
AB  - The doctor's oath to serve the good of the patient requires the recognition that
      the patient's good consists of more than simply his or her biomedical health
      status. This article proposes a scheme for identifying the primary decision maker
      in clinical settings, particularly when the patient's own decision-making
      capacity is in question. A few of the many ethical controversies encountered in
      the practice of trauma medicine are examined and discussed.

PMID- 8252445
TI  - Another dental miracle.

PMID- 8252446
TI  - Achieving success: moving beyond the comfort level.
AB  - Understanding the stages of growth, saturation and transition is the first step
      to setting meaningful career goals. While this concept is fairly new in
      dentistry, it is not new in other commercial enterprises. Business managers and
      owners have known for decades that growth stagnates after a period of time. At
      that point, a new infusion of energy and a reformation of the business's
      objectives and methods are needed to launch forward into the next phase of
      growth. Transition management in dentistry represents periods of growth that are
      followed by saturation and a comparatively rapid changeover to a new practice
      form. Saturation occurs when the clinical capacity of a practice is exceeded by
      the needs of a growing patient base. The key transitions in the career of a
      dentist are those from school to practising, and practising to retirement. A
      great number of dentists (due to low motivation, the comfort level or poor
      management skills) never reach the saturation point during their practising
      career. For these dentists, starting out and retirement are the only transitions
      that will ever apply to them. Dentists evaluating transition options must first
      identify which career stage they belong to since their objectives will be
      different at each stage. Dentists in the growth phase should focus on practice
      management and achieving saturation before attempting a transition. Since
      transitions like start-up, retirement, partnerships, associateships and buy-ins
      have pivotal roles in the life cycle of a practice, transitions must be managed
      carefully to achieve successful results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252447
TI  - Decades in dentistry and the CDA RIF: introducing a new initiative and a new
      product.

PMID- 8252448
TI  - Child abuse: implications for the dental health professional.

PMID- 8252449
TI  - Elder abuse and neglect: a concern for the dental profession.
AB  - Although elder abuse and neglect are not new problems, the dental profession is
      just now beginning to turn its attention to their research, detection, and
      prevention. Dentists are in an ideal position to diagnose and treat older
      patients who present with injuries to the head and neck area. This article
      provides information on the risk factors and indicators for elder abuse and
      neglect. Intervention strategies are suggested and community resources are
      listed. It is strongly recommended that mandatory family violence courses should
      be incorporated into the dental curriculum, and that dentists recognize the need
      for multi-disciplinary cooperation when dealing with mistreated older adults.

PMID- 8252450
TI  - Elder abuse and the dentists' awareness and knowledge of the problem--a national
      survey.
AB  - A national sample of 1,775 Canadian dentists, representing 13.2 per cent of all
      Canadian dentists, were evaluated via a mailed questionnaire about their
      knowledge, awareness of, and experiences with victims of elder abuse and/or
      neglect. In all, 83.3 per cent of respondents were aware, to varying extents, of
      elder abuse or neglect. Of the dentists observing a patient suspected to have
      been a victim of neglect or abuse, 40.6 per cent reported incidents of neglect,
      while physical abuse was seen 59.4 per cent of the time. The types of neglect
      most frequently observed included: neglect of personal hygiene (31.8 per cent),
      failure to provide adequate medical/dental care (30.2 per cent), and failure to
      provide adequate supervision (20.1 per cent). The most frequently reported signs
      of physical abuse were bruises and welts (21.8 per cent), broken denture
      prostheses (12.1 per cent), fractured and avulsed teeth (11.5 per cent), and
      abrasions and lacerations (10.3 per cent). Where abuse was observed, dentists
      provided dental treatment in 53.2 per cent of the cases and made emergency
      medical referrals in 20.3 per cent of the cases. This study demonstrates that
      dentists have identified cases of abuse and/or neglect, and therefore should be
      consulted in the abuse/neglect identification and assessment process.

PMID- 8252451
TI  - The glandular odontogenic cyst, a rare lesion that tends to recur.
AB  - This article reports an example of a rare, recently reported odontogenic cyst,
      the glandular odontogenic cyst. It is important because it can become quite large
      and tends to recur if treated by curettage or enucleation.

PMID- 8252452
TI  - Osteosarcoma and fibrous dysplasia: radiographic features in the differential
      diagnosis: a case report.
AB  - A case of osteosarcoma misdiagnosed as fibrous dysplasia is presented to
      demonstrate the importance of an integrated diagnostic approach to oral lesions.
      The clinical and radiographic differences between fibrous dysplasia and
      osteosarcoma are reviewed.

PMID- 8252453
TI  - Errors in the diagnosis of oral malignancies.

PMID- 8252454
TI  - Two to five year follow-up of Harris-Galante cementless total hip arthroplasty.
AB  - One hundred and forty-nine hips (125 patients) underwent cementless Harris
      Galante primary total hip arthroplasty from September 1987 to June 1990 at the
      Taichung Veterans General Hospital. Seventy hips (61 patients) have been followed
      up for at least 2 years (range, 26-55 months, mean 36 months). The primary
      diagnoses included osteoarthritis (42.9%) and avascular necrosis (57.1%). All the
      hips were evaluated using Harris hip score and Mayo Clinic hip score. The average
      Harris hip score was 36.5 points (23-73) preoperatively, and 95 points (80-100)
      postoperatively. When evaluated by the Harris hip score, 94.3% were excellent,
      and 5.7% had good results; and 90% were excellent, 10% had good results when
      evaluated by Mayo Clinic hip score. No fair or poor results were noted by either
      evaluating system. Fifty-seven femoral components (81.4%) appeared to have stable
      bone ingrowth fixation, ten components (14.3%) had stable fibrous ingrowth, and
      three (4.3%) were unstable. Fifty-five hips (78.6%) showed radiolucent lines
      around the femoral component in follow-up roentgenogram; most were at the non
      porous, fiber-mesh part. It seemed that there was no correlation between these
      radiolucent lines and clinical outcome, according to this short-term study.

PMID- 8252455
TI  - The reversal effect of low dose aminophylline on thiopental-induced sedation.
AB  - Fifty-two ASA (American Society of Anesthesiologists) class I-II female patients,
      from 22 to 66 years of age, undergoing D & C (dilatation and curettage)
      procedure, were randomly divided into 2 groups in a double-blind and placebo
      controlled design to investigate whether aminophylline could reverse the sedative
      effect of thiopental. Patients of both groups were anesthetized with fentanyl (2
      micrograms/kg, i.v.) and thiopental (4 mg/kg, i.v. and 1 mg/kg, i.v. repeated if
      necessary). Postoperatively, they were intravenously given aminophylline (2
      mg/kg) or normal saline in an equal volume solution over 5 minutes. The results
      showed that patients in the aminophylline group were more sedated (p < 0.05) than
      in the saline group 5 minutes after reversal, but were less sedated (p < 0.05) at
      minute 20. No significant differences between groups were found at other times.
      The total time spent in the postanesthetic unit was shorter in the aminophylline
      group (92 +/- 27 min.) than in the normal saline group (109 +/- 30 min.) (p <
      0.05). The serum theophylline levels in some cases in the aminophylline group
      ranged between 3.2 and 4.9 micrograms/ml (4.3 +/- 0.7 micrograms/ml, n = 10). No
      apparent side effects, including tachyarrhythmias, were noted. We conclude that
      low dose aminophylline (2 mg/kg, i.v.) can partially reverse thiopental-induced
      sedation with safety in the early phase of recovery and it can reduce the total
      time spent in the postanesthetic unit.

PMID- 8252456
TI  - Sclerosing hemangioma of the lung: a clinicopathologic study.
AB  - The clinical and pathological features of 11 cases with sclerosing hemangiomas of
      the lung seen between 1982, and 1992 were reviewed. There were 1 male and 10
      female patients aged 15 to 74 years (mean age, 53 years) at operation. Among the
      11, 4 were asymptomatic, with the tumor discovered only on routine chest
      roentgenograms. All 11 patients had a solitary tumor showing as a well-defined
      homogeneous round or oval shadow on chest x-rays. Microscopically, 8 of the 11
      tumors consisted of a mixture of the four major patterns: hemorrhagic, sclerotic,
      papillary and solid. Five patients received enucleation; four, wedge resection;
      one, segmentectomy and one, lobectomy. Since this tumor is usually clinically
      benign and surgically curative, thoracotomy and complete removal of the tumor by
      limited resection is recommended.

PMID- 8252457
TI  - Community-based study on the relationship between serum cholesterol/triglyceride
      and dietary habits/life styles in Pu-Li, Taiwan.
AB  - This is a community-based study on the relationship between serum cholesterol
      (CHO)/triglyceride (TG) and dietary habits/life styles of persons living in a
      central Taiwan Town. Door-to-door interviews were carried out by the Yang-Ming
      Crusade, and fasting blood for CHO and TG tests was drawn by public health nurses
      from Pu-Li Health Station. Univariate analysis found that significant variables
      correlated with CHO were age (+), locality, non-fish seafood (+) and pungent food
      (+). Significant variables correlated with TG were age (+), sex, locality,
      smoking (+), alcohol (+) and physical activity (-). Stratified by age (> or = 50
      and < 50) and by sex respectively, only one significant interaction item--age x
      organ meat consumption--was found; those who consumed organ meat more frequently
      had higher TG, if they were less than 50 years of age. This was not true for
      those aged 50 and over. Multivariate analysis using logistic regression revealed
      that after controlling for all of the other covariates, significant variables
      correlated with CHO were age (OR = 1.92, 95% C.I. = 1.37-2.69), pungent food (OR
      = 1.91, 95% C.I. = 1.26-2.89); locality (OR = 0.53, 95% C.I. = 0.35-0.80 for sub
      urban area; and OR = 0.74, 95% C.I. = 0.50-1.08 for rural area); sea food
      consumption (OR = 1.50, 95% C.I. = 0.94-2.40); and smoking (OR = 0.69, 95% C.I. =
      0.48-0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252458
TI  - [Comparison of food specific IgE antibody test (RAST) and skin tests in children
      with atopic dermatitis].
AB  - Thirty children with atopic dermatitis were enrolled in our study to evaluate the
      food specific IgE antibody assay (RAST) and skin tests as a screening test for
      food hypersensitivity. Our results showed that eight food antigens (fish, shrimp,
      crab, soybean, milk, egg-white, peanut, wheat) frequently elicited positive
      hypersensitivity reactions. Twenty-four patients had at least a positive skin
      reaction to one of the foods tested. Of the 240 skin tests, 30% (72/240) yield
      positive reactions. Eighteen patients had at least a positive RAST reaction to
      one of the foods tested, 20.9% (50/240) yield positive reaction. The agreement
      between skin test and RAST was 79.6%. Crab and shrimp accounted for most frequent
      positive reaction in both tests. The skin tests produced more positive results in
      skin testing than RAST, but gave a higher frequency of false positive results.
      The diagnosis of food allergy may be suspected from the medical history or by
      food specific IgE antibodies together with skin test as a screening test.
      Furthermore, the double blind placebo controlled food challenge should be
      considered as standard for clinical investigations.

PMID- 8252459
TI  - [The chemical shift imaging of liver].
AB  - Tissue characterization of different pathologies of the liver can be achieved by
      differences of relaxation time on changing of pulse sequences in magnetic
      resonance imaging (MRI). The usefulness of MRI for detection of liver disease is
      limited when the pathological change is subtle. Chemical shift is a fundamental
      characteristics in nuclear magnetic resonance (NMR). Chemical shift imaging (CSI)
      in MRI is based on the different Larmor frequency of proton in water and fat; and
      therefore it was able to enhance the effectiveness of pathology. For this study,
      Dixon's method was used to detect liver pathologies and compare its detectability
      with conventional pulse sequences. Forty cases were enrolled for study; they
      included 5 health volunteers, 15 hepatomas, 1 cholangiocarcinoma, 5 metastatic
      hepatic tumors and 14 fatty livers. In hepatic tumors, the lesion number, tumor
      margination and lesion-to-liver contrast in images were read and analyzed. Signal
      intensities, signal-to-noise ratio and contrast-to-noise ratio were compared,
      after measurement, from stored data. In fatty livers, the relative change of
      signal intensities in different areas of the liver in in-phase and out-phase
      images were compared with the back muscle and spleen to find where the fatty
      metamorphosis happened. CSI in spin echo or gradient echo pulse sequences was
      found to be adequate and valuable for detecting fatty liver, when compared with
      conventional MRI. CSI not only identified the extension of disease itself but
      also characterized the fatty change in liver parenchyma. Though CSI affords no
      further advantages than conventional pulse sequences for detection of hepatic
      tumors, occasionally, when the image quality of the conventional pulse sequences
      is not satisfactory or equivocal in lesion detection, the use of CSI might be
      attempted.

PMID- 8252460
TI  - [Surgical management of blunt renal trauma].
AB  - From 1986 to 1990, 26 patients with blunt renal trauma were hospitalized and
      received surgery in this Hospital. Included were 23 males and 3 females with a
      mean age of 28.6 years (range: 5 to 82). The mean duration of follow-up was 37
      months. The severity of renal injury was classified by using the renal injury
      scale which was published by the Organ Injury Scaling (O.I.S.) Committee of the
      American Association for the Surgery of Trauma (A.A.S.T.) in 1989. According to
      operative findings, the renal injuries of the 26 cases were classified as
      follows: Grade I, 3 cases; Grade II, 4 cases; Grade III, 2 cases; Grade IV, 6
      cases; and Grade V, 12 cases. One case had bilateral renal injuries. Among the
      patients, four were treated with drainage. Three cases underwent repair and
      drainage. One case was treated with partial nephrectomy. Nineteen cases underwent
      nephrectomy. The mortality rate was 7.6% and the morbidity rate, 15.2%. The most
      frequent postoperative complications related to renal injury in the patients who
      survived initial operation were intra-abdominal abscesses (3.8%), small bowel
      obstruction (3.8%), pulmonary infection (3.8%) and pancreatitis (3.8%).

PMID- 8252461
TI  - Factor VII deficiency with intracranial hemorrhage: a case report.
AB  - Factor VII deficiency is an autosomal recessive hereditary disorder characterized
      by a normal partial thromboplastin time and a prolonged prothrombin time.
      Definite diagnosis of this condition requires a specific Factor VII assay. Its
      quite uncommon occurrence in the newborn was first described by Alexander and
      associates in 1951. A one-day-old male, full-term newborn was presented here with
      skin pallor, respiratory distress and bitemporal bulging masses noted immediately
      after birth. Computed tomography scan of the brain revealed a subgaleal hematoma
      and subarachnoid hemorrhage. Laboratory studies revealed prolonged prothrombin
      time and a Factor VII level less than 1%. Literature on the clinical
      manifestation and management of Factor VII deficiency is reviewed briefly.

PMID- 8252462
TI  - Bilateral traumatic chylothorax: a complication of fracture-dislocation of the T
      spine.
AB  - Traumatic chylothorax is a rare complication of fracture-dislocation of the
      thoracic spine. Not treated adequately, it will be associated with high mortality
      and morbidity. A review of the English literature shows that bilateral traumatic
      chylothorax is rarely discussed. A case is presented of fracture-dislocation of
      the third thoracic vertebra combined with bilateral traumatic chylothorax
      following a motor vehicle accident. The mechanism of injury is described. The
      management strategies are, initially, conservative treatment including chest tube
      drainage, NPO with total parenteral nutrition (TPN), followed by medium-chain
      triglyceride diet. Without improvement, surgical measures such as mediastinal
      ligation of the thoracic duct should be considered.

PMID- 8252463
TI  - Epiphyseal fracture-retrosternal dislocation of the medial end of the clavicle: a
      case report.
AB  - Epiphyseal fracture-retrosternal dislocation of the medeial end of the clavicle
      is an unusual injury. It may occur as a result of a blow either indirectly on the
      posterolateral aspect of the shoulder girdle or directly over the sternal end of
      the clavicle. It is clinically impossible to differentiate from the true
      posterior dislocation even with the computed tomography, but the treatment for
      either lesion is the same. Recently we uneventually treated a 15-year-old boy
      with conservative treatment and got a satisfactory result. The purpose of this
      paper is to draw the attention of the readers to the rarity and serious nature of
      such injury and the potential difficulties in establishing diagnosis and
      achieving reduction.

PMID- 8252464
TI  - Primary nasal melanoma with exclusive liver metastasis: a case report.
AB  - A 50-year-old male presented with a nasal mass causing obstruction and bleeding.
      The initial biopsy indicated a malignant lymphoma but the subsequent biopsy
      diagnosed an undifferentiated carcinoma. However, histopathological study and
      immunohistochemical study, made a final diagnosis of nasal melanoma. Six months
      after the diagnosis, the patient developed exclusive liver metastasis. He
      responded to 1 course of intensive chemotherapy with 200 mg/m2 cisplatin and 5000
      mg/m2 dacarbazine for 6 months. For patients with nasal cavity malignancy, the
      possibility of primary melanoma should be considered. Combination chemotherapy
      with intensive dose of cisplatin and dacarbazine may be a viable treatment
      regimen for nasal melanoma with liver metastasis.

PMID- 8252465
TI  - Malignant duodenocolic fistula: a case report.
AB  - A 65 year-old female presented with diarrhea, body weight loss, malnutrition,
      elevated serum carcinoembryonic antigen (CEA) and electrolyte disturbances. A
      series of examinations showed colon cancer with a malignant duodenocolic fistula.
      Patient received extended right hemicolectomy with wide local excision of the
      duodenum (en bloc resection of the tumor). Recovery was smooth without local
      recurrence or metastasis after a six-month follow-up. Wide en bloc resection
      provides the only hope of cure in such cases. Treatment with extended right
      hemicolectomy with Whipple's procedure, or extended right hemicolectomy with
      extended local wide excision of duodenum, should be chosen, depending upon the
      extent of tumor invasion.

PMID- 8252466
TI  - [Pulmonary edema in transcervical endometrial ablation: a case report].
AB  - The use of the transcervical resectoscope for endometrial ablation and/or
      resection of myomas is a relatively new technique in gynecologic surgery.
      Although complications are uncommon with this procedure, they can occasionally
      appear and lead to potential hazard. Here a patient presenting for endometrial
      ablation is described; 1.5% glycine was used as the irrigation solution to
      enhance visibility and to wash away blood and tissue particles. Unfortunately, a
      large amount of glycine was absorbed by the open vessels in the myometrium during
      operation, leading to pulmonary edema and dilutional hyponatremia. After
      administration of diuretics, sodium supplement and 100% oxygen, complications
      improved progressively. The patient was discharged on postoperative day 5 without
      any sequelae.

PMID- 8252467
TI  - Peripheral nerve sheath tumors. Histogenesis, classification, and prognosis.

PMID- 8252468
TI  - Clinical trials of agents that reverse multidrug resistance. A literature review.
AB  - BACKGROUND: The discovery of the P-170 glycoprotein as a mediator of multidrug
      resistance (MDR) represents one of the most important research accomplishments in
      antineoplastic pharmacology during the last decade. Demonstration of P-170 in
      epithelial tissues, untreated and chemotherapeutically pretreated human
      malignancies, and identification of various agents capable of reversing
      resistance in vitro generated enthusiasm for clinical studies throughout the
      world. The authors provide an overview of the current status of clinical
      investigations of MDR1 reversing agents in hematologic and solid malignancies.
      METHODS: The authors performed an extensive literature search and selected more
      than 70 articles concerning the potential clinical relevance of P
      glycoprotein/MDR1 modulating agents. Information abstracted included type of
      reverting agent and chemotherapeutic regimen, number of patients, tumor type,
      histologic proof of P-glycoprotein expression, and objective response rates.
      RESULTS: Proof of the involvement of MDR1 in clinical drug resistance has been
      slow to accumulate, primarily because of difficulties in adapting assays of MDR1
      expression and in planning appropriate trials. Pilot studies have shown that
      verapamil, cyclosporine, and other chemosensitizers may reverse resistance in a
      subset of patients, but significant (cardiovascular) side effects are common. For
      leukemias, lymphomas, and multiple myeloma, response rates of 60-80% may be
      achieved with the potential for cure, whereas in solid tumors, only a few
      patients appear to benefit. CONCLUSIONS: Because of predominantly negative
      results and unanswered fundamental questions regarding the biology of P
      glycoprotein, additional clinical trials with less toxic modulators or their
      combination are appropriate to delineate optimal strategies for MDR1 reversal and
      to define the spectrum of responsive tumors. Additional attention also must be
      given to the coexistence of other resistance mechanisms that may offer separate
      opportunities for modulation.

PMID- 8252469
TI  - DNA stem line heterogeneity in esophageal cancer accurately identified by flow
      cytometric analysis.
AB  - BACKGROUND: This study was designed to evaluate the importance of DNA stem line
      heterogeneity in determining the malignant potential of esophageal cancer.
      METHODS: Flow cytometric analysis of intratumor heterogeneity of DNA contents was
      performed on step-sectioned slices of 57 resected esophageal carcinomas. RESULTS:
      DNA stem line heterogeneity, as assessed by DNA content measurements, was present
      in 25 (44%) tumors; 6 (11%) were a combination of diploid and aneuploid DNA
      pattern, and 19 (33%) had two or more aneuploid peaks with different DNA contents
      (multiploid). Of the remaining 32 homogeneous tumors, 4 showed only a diploid DNA
      pattern in all samples examined, whereas 28 tumors had only the aneuploid
      pattern. Tumors with the heterogeneous DNA pattern had a significantly higher
      frequency of lymph node metastasis than did those with the homogeneous DNA
      pattern (P < 0.05). CONCLUSIONS: For evaluation of the highly malignant potential
      of esophageal carcinoma by nuclear DNA contents, it is important to identify
      accurately intratumoral heterogeneity. Because different DNA stem lines were
      evident in different areas of the lesion, evaluation of multiple specimens from a
      wide area of each lesion is needed to determine with accuracy the degree of
      intratumor DNA stem line heterogeneity.

PMID- 8252470
TI  - An immunohistochemical analysis for cancer of the esophagus using monoclonal
      antibodies specific for modified nucleosides.
AB  - BACKGROUND: Modified nucleosides such as 1-methyl-adenosine and pseudouridine
      exist as minute components of transfer ribonucleic acid (tRNA) and are excreted
      in the urine in large amounts in the presence of malignancy. Although use of
      these modified nucleosides as tumor markers has long been studied and many
      reports have detailed their relationship with malignant tumors and the urinary
      excretion of various modified nucleosides, there have been no reports on modified
      nucleosides in esophageal carcinoma. METHODS: Monoclonal antibody patterns
      against 1-methyladenosine and pseudouridine were studied in esophageal carcinoma,
      freshly resected esophageal carcinoma tissue specimens fixed in 10% neutral
      formaldehyde solution, embedded in paraffin, and sectioned for
      immunohistochemical study. Inhibition enzyme-linked immunosorbent assay (ELISA)
      was used to examine urinary excretion of these modified nucleosides in patients
      with esophageal carcinoma. RESULTS: Although rare in normal esophageal
      epithelium, these modified nucleosides were strongly stained in esophageal
      carcinoma cells. Most carcinoma cells exhibited a cytoplasmic pattern, although
      some cells at the infiltrating edge displayed a nuclear pattern. These modified
      nucleosides were intensely imaged in 11 of 12 cultured esophageal cell lines, the
      exception being one line that had a much longer doubling time. Using ELISA,
      urinary excretion of these modified nucleosides was found to be significantly
      higher in patients with esophageal carcinoma than in healthy subjects; such
      excretion correlated with carcinoma size and stage and tended to decrease after
      treatment. CONCLUSIONS: These findings indicate that the modified nucleosides 1
      methyladenosine and pseudouridine may be useful as tumor markers for esophageal
      carcinoma.

PMID- 8252471
TI  - Prognostic value of DNA analysis in colorectal carcinoma.
AB  - BACKGROUND: Reported experiences regarding the prognostic significance of DNA
      content in colorectal carcinoma have been a matter of controversy. METHODS: DNA
      analysis with image cytometry was performed in 137 patients with colorectal
      cancer. Only patients who had resection without tumor residual and who did not
      die postoperatively as a consequence of the operation were entered in the study.
      At the time of DNA analysis, neither the histomorphologic data nor the relapse
      free survival time of the patients were known. RESULTS: In this investigation the
      DNA content of tumor cells had no univariate or multivariate influence on the
      relapse-free survival time. The prognosis was dependent on the tumor
      localization, depth of tumor infiltration, lymph node metastasis, and grade.
      CONCLUSIONS: DNA content provides no additional prognostic information in
      colorectal carcinoma.

PMID- 8252472
TI  - The value of the preoperative mucosal biopsy in the diagnosis of colorectal
      mucinous adenocarcinoma.
AB  - BACKGROUND: As a rule, mucinous colorectal adenocarcinomas tend to be at a more
      advanced stage at the time of discovery than their nonmucinous counterparts. This
      study assesses the potential value of the preoperative biopsy in the diagnosis of
      such mucinous adenocarcinomas. METHODS: The preoperative biopsy specimens and the
      corresponding resection specimens of 189 patients with colorectal carcinomas were
      examined and compared by conventional light microscopic study. The stage of the
      tumor, using the modified Dukes classification of Astler and Coller, was
      correlated with the percentage of mucinous component (MC) in the resection
      specimens. The MC in the preoperative biopsy was assessed by the presence of: (1)
      malignant-appearing glands disrupted by the presence of abundant extruded
      intraluminal mucin; (2) pools of mucin in the connective stroma of the
      adenocarcinoma; and (3) superficial pools of mucin containing ribbons or clusters
      of neoplastic epithelial cells. RESULTS: The presence of a significant (more than
      25%) MC in the resection specimen correlated well with an advanced stage of the
      tumor; 82% of tumors with more than 25% MC were at the B2 or higher stage,
      compared with 64% of tumors with less than 25% MC (P < 0.05). Finding MC in the
      preoperative biopsy correlated well with a similar finding in the resection
      specimen and with a B2 or higher stage of the tumor in such specimens; 83% of MC
      positive biopsy specimens exhibited more than 25% MC in the corresponding
      resection specimen, whereas only 10% of MC-negative biopsy specimens were
      associated with a surgical specimen containing more than 25% MC (P < 0.001).
      Similarly, 83% of such MC-positive biopsy specimens revealed a carcinoma at the
      B2 or higher stage upon resection, compared with 63% of the MC-negative biopsy
      specimens (P < 0.02). CONCLUSIONS: Colorectal adenocarcinomas showing MC in the
      preoperative biopsy are significantly more likely to reveal a high mucin content
      and to be at an advanced stage at resection. Thus, such preoperative findings
      should be recorded and made available on a prospective basis to the treating
      physicians.

PMID- 8252473
TI  - Effects of preoperative transcatheter hepatic arterial chemoembolization for
      hepatocellular carcinoma. The relationship between postoperative course and tumor
      necrosis.
AB  - BACKGROUND: The effects of preoperative transcatheter arterial chemoembolization
      (TAE) for hepatocellular carcinoma (HCC) remain a matter of controversy. METHODS:
      Seventy-two patients with HCC were entered in the study; the patients did not
      have the risk factors for disease recurrence of tumor larger than 5 cm in
      diameter, the presence of venous invasion, or intrahepatic metastasis. Only
      patients with 3 years of follow-up after curative resection were selected. Forty
      six underwent TAE (Group I) and 26 did not undergo TAE (Group II). Group I was
      divided into three subgroups according to the degree of tumor necrosis: IA,
      complete necrosis; IB, partial necrosis; and IC, no necrosis. Group II was
      divided into two subgroups: IIB, partial necrosis; and IIC, no necrosis. RESULTS:
      Preoperative TAE did not improve the average disease-free survival rates of the
      group as a whole. For patients undergoing TAE, the survival rate of Group IB was
      significantly worse than that of Groups IA or IC. The survival rate of Group IB
      was worse than that of Group II, but the difference was not significant. In Group
      II, the survival of Group IIB was worse than that of Group IIC. Histologically,
      residual tumor cells lacking mutual contact were detected in some patients in
      Group IB. CONCLUSION: These results indicate that partial tumor necrosis caused
      by preoperative TAE or spontaneous tumor necrosis per se might facilitate
      postoperative disease recurrence. This may occur because in patients with partial
      necrosis, the remaining tumor cells are less firmly attached and more likely to
      be dislodged into the bloodstream during hepatic resection.

PMID- 8252474
TI  - Loxiglumide (CR1505), a cholecystokinin antagonist, specifically inhibits the
      growth of human pancreatic cancer lines xenografted into nude mice.
AB  - BACKGROUND: Cholecystokinin is thought to be an important factor regulating the
      growth of human pancreatic cancers. The study was designed to evaluate the
      effects of the cholecystokinin antagonist loxiglumide (CR1505) on the growth of
      human pancreatic cancer. METHODS: Human gastrointestinal cancer xenografted
      tumors (one esophageal, one gastric, two colorectal, two biliary tract, and two
      pancreatic cancers) were transplanted into nude mice. The mice were given CR1505
      at 250 mg/kg daily for 14 days, either subcutaneously or intragastrically, and
      the tumor volumes before and after treatment were compared. In vitro effects of
      CR1505 were assessed by measuring the DNA synthesis (3H-thymidine incorporation).
      RESULTS: CR1505 inhibited the growth of the two pancreatic cancer lines but did
      not inhibit the growth of the other lines. CR1505 also inhibited in vitro DNA
      synthesis in the two pancreatic cancer lines at lower concentrations than in the
      other lines. This pancreatic cancer-specific inhibitory effect of CR1505 was
      retarded by exogenously administered cholecystokinin in one pancreatic cancer
      line but was augmented in the other line. The effect of CR1505 was inhibited by
      oral administration of the trypsin-inhibitor camostate (FOY-305) in both
      pancreatic cancer lines. CONCLUSIONS: These results suggest that CR1505 may
      specifically inhibit the growth of human pancreatic cancers and may be suitable
      for clinical study. However, its antiproliferative effect may not necessarily be
      dependent on its cholecystokinin-antagonism but may be mediated through the
      proteolytic enzymes found in the lysosomes of the pancreatic cancer cells.

PMID- 8252475
TI  - A different profile of epitopic dominance in the immunoglobulin G response to
      bovine betalactoglobulin in lung cancer.
AB  - BACKGROUND: The authors previously documented a quantitative defect in the
      immunoglobulin G (IgG) response toward bovine betalactoglobulin (BLG), the major
      cow's milk antigen, and antigen p1 of the house dust mite, Dermatophagoides
      pteronyssinus (Der p1), in patients with lung cancer. In the Der p1 model, the
      authors documented at the IgG level an epitope specificity that differed between
      patients with lung cancer (preferential specificity for cryptic epitopes) and
      healthy control subjects and patients with mite allergy. The current study
      investigated whether this varying specificity might be extended to the IgG
      response toward BLG. METHODS: The authors compared the IgG binding to native BLG
      (nBLG) and its products of pepsin hydrolysis (dBLG) in a solid-phase enzyme
      linked immunosorbent assay (ELISA) using peroxidase-conjugated protein A in 120
      patients with lung cancer, 52 patients with chronic obstructive pulmonary disease
      (COPD) who were closely matched for age, sex, and smoking habits with the
      patients with cancer, and 120 healthy control subjects (blood donors). RESULTS:
      Expressing the ratio between optical densities observed for dBLG and nBLG,
      respectively, the authors documented two groups: patient with lung cancer with
      higher levels of binding on dBLG (mean ratio +/- SD, 1.66 +/- 0.26) and healthy
      control subjects and patients with COPD with similar levels of retention for dBLG
      and nBLG (mean ratios +/- SD, 1.00 +/- 0.10 and 1.01 +/- 0.07, respectively).
      Influence of population characteristics could be excluded. The histologic type of
      cancer and its extent had no influence on the defined ratio. CONCLUSION: These
      results suggest a preferential recognition of epitopes unmasked by pepsin
      hydrolysis (cryptic epitopes?) by lung cancer IgG, contrasting with the
      preferential specificity of IgG from healthy control subjects and patients with
      COPD for structural epitopes unaffected by the proteolysis. These findings are
      similar to those observed previously with Der p1 and indicate a varying, and
      possibly specific, profile of epitopic dominance in the IgG response to antigens
      naturally presented at the mucosal level in patients with lung carcinoma, a model
      of mucosal cancer.

PMID- 8252476
TI  - Successful treatment of a patient with adult T-cell leukemia by daily oral
      administration of low-dose etoposide. Decrease in the amount of HTLV-I proviral
      DNA revealed by the polymerase chain reaction method.
AB  - BACKGROUND: Oral administration of low-dose etoposide is known to be effective
      against various malignancies, including malignant lymphoma. However, the
      effectiveness of low-dose etoposide as a treatment for adult T-cell leukemia
      (ATL) has not been established. METHODS: A 74-year-old woman with ATL in acute
      phase was treated by daily oral administration of low-dose etoposide (25 mg/m2).
      The authors assayed changes in the surface markers and the amount of human T-cell
      lymphotropic virus type I (HTLV-I) proviral DNA in peripheral blood mononuclear
      cells (PBMC) by using flow cytometry and the polymerase chain reaction (PCR)
      method, respectively. RESULTS: Before treatment, generalized lymphadenopathy and
      hepatomegaly were observed. In laboratory examination, the leukocyte count was
      13.7 x 10(3)/microliters, with 65% abnormal lymphocytes. The percentages of CD3-,
      CD4-, and CD25-positive cells in PBMC were 84.4%, 84.4%, and 76.5%, respectively.
      The serum lactic dehydrogenase (LDH) level was 1376 IU/l (normal range, less than
      520 IU/l). After the initiation of treatment, lymph-adenopathy and hepatomegaly
      disappeared, and the serum LDH level was reduced to the normal level before the
      20th day of the treatment. On the 55th day of the treatment, CD25-positive cells
      had virtually disappeared. In addition, the amount of the proviral DNA in PBMC
      was reduced to approximately one-tenth by this treatment. Subsequently, the
      patient was in remission for more than 16 months. No side effects were observed.
      CONCLUSIONS: Daily oral administration of low-dose etoposide can be a safe and
      effective treatment for patients with ATL. The authors believe this to be the
      first report of a patient with ATL in whom complete remission (CR) was achieved
      by this treatment.

PMID- 8252477
TI  - Glandular peripheral nerve sheath tumors.
AB  - BACKGROUND: Peripheral nerve tumors (PNT) containing glands are uncommon. Which
      types of PNT contain glands is a matter of controversy, a factor bearing on the
      prognosis of these tumors. METHODS: The authors reviewed the files of 11 patients
      with glandular PNT seen in their laboratory and 27 patients reported in the
      literature. RESULTS: The 11 instances of glandular PNT seen in their laboratory
      affected male and female patients equally; patients ages ranged from 8 to 68
      years (mean, 28 years). Six patients had neurofibromatosis-1 (NF-1). Eleven of
      the tumors were histologically malignant PNT, and one was a benign neurofibroma.
      There were no schwannomas (neurilemomas). The glands were discrete, usually
      localized to a few areas and in every patient were lined by a keratin-positive
      epithelium, which in two patients was malignant. One tumor also contained areas
      of rhabdomyosarcoma, chondrosarcoma, and osteosarcoma (a pluridirectional
      malignant PNT). Treatment in all patients was some form of surgical resection,
      followed by radiation in three and chemotherapy in two. Follow-up data were
      available for nine patients; six of eight patients died with disease. Review of
      the literature revealed two purported glandular schwannomas (neurilemomas). The
      authors think these patients had schwannomas containing trapped skin adnexa.
      Overall, 74% of the patients had NF-1. Ninety-two percent of the tumors were
      histologically malignant, and 23% of the malignant tumors were pluridirectional
      malignant PNT. Of the 21 patients for whom follow-up was available, 71% died with
      tumor. CONCLUSION: Most glandular PNT are histologically malignant and often are
      fatal.

PMID- 8252478
TI  - Clinical epidemiology of bilateral breast cancer.
AB  - BACKGROUND: The clinical epidemiology of bilateral breast cancer was assessed in
      a population-based study from Saarland, Germany. METHODS: Clinical aspects of
      breast cancer, including age and tumor spread at diagnosis and survival, were
      compared between 251 patients with bilateral breast cancer and all 9585 patients
      with a first diagnosis of breast cancer registered with the population-based
      cancer registry of Saarland, Germany, between 1968 to 1987. RESULTS: The patients
      with bilateral breast cancer were on average considerably younger at the time of
      diagnosis of the first breast cancer than the total group of patients with breast
      cancer (mean age, 55.7 years versus 60.5 years). Overall, the distribution of
      tumor spread at diagnosis of the second breast cancers was similar to the
      corresponding distribution of first breast cancers, but a much less favorable
      distribution was observed among second breast cancers that developed in women
      younger than 50 years of age. The survival rates after diagnosis of a second
      breast cancer were much worse than the survival rates after a first breast cancer
      diagnosis. These differences persisted after control for important covariates
      such as age and tumor spread and were more pronounced if the first tumor was
      diagnosed in an advanced stage and if the time interval between diagnosis of the
      first and second cancers was short. Nevertheless, tumor spread at diagnosis of
      the second cancer was by far the most important predictor of survival among
      patients with bilateral breast cancer. CONCLUSIONS: The differences in clinical
      aspects of first and second breast cancers should be considered in clinical
      management of patients with breast cancer. Further research is required to
      explain these differences.

PMID- 8252479
TI  - Breast cancer screening in an urban public hospital. Five-year results.
AB  - BACKGROUND: This report describes the first 5 years of the Breast Cancer
      Screening Program (BCSP) at Cook County Hospital (CCH), a hospital that serves a
      predominantly African-American and low-income population. METHODS: A
      retrospective review of hospital cancer registry staging for breast cancers
      diagnosed between 1984 and 1988 was performed. RESULTS: Between 1984 and 1988,
      499 new breast cancers were diagnosed at CCH, of which 33% were diagnosed after
      referral from the BCSP. The percentage of early breast cancers, defined as Stages
      0 or 1, was 25% in women referred from the BCSP, compared with 6% for women
      referred from other clinical areas (P < 0.001). During this same period of time,
      the proportion of women at CCH with localized breast cancer increased from 30% in
      1980-1983 to 40% from 1984-1988 (P < 0.05), an increase that can be attributed to
      the BCSP. Only 21% of the breast cancers detected by the BCSP were found by
      mammography alone. Of these, 91% were localized. CONCLUSIONS: The BCSP has had an
      impact on the proportion of early breast cancer diagnosed at CCH. Despite these
      efforts, the proportion of early breast cancer diagnosed at CCH (12%) is
      significantly less than that seen for all African-American women with breast
      cancer in Illinois (32%; P < 0.001).

PMID- 8252480
TI  - Overexpression of p53 and prognosis in breast cancer.
AB  - BACKGROUND: Assessment of prognostic markers in breast cancer independent of the
      axillary lymph node status is of major concern for the application of adjuvant
      treatment regimens. The current treatment decision is based mainly on the
      axillary lymph node status. Because of improved screening methods, the number and
      proportion of patients with node-negative disease are increasing, which warrants
      a search for reliable prognostic parameters. The application of tumor suppressor
      gene expression appears to be especially suited as a marker of the progress in
      malignant cellular dedifferentiation. METHODS: Tumor tissues of 156 patients with
      primary invasive breast cancer were analyzed immunohistochemically for the
      presence of p53 protein in paraffin-embedded material. The reaction to monoclonal
      antibody PAb1801 yielded better results than did reactions to monoclonal antibody
      DO1 and polyclonal antibody CM-1. The significance of the immunohistochemical
      data was compared with a panel of established risk factors. RESULTS: Nuclear
      accumulation of p53 protein proved to be an independent marker of
      dedifferentiation, regardless of the lymph node status. Tumors showing p53
      immunoreactivity were significantly more often related with histological Grade 3
      and the absence of steroid hormone receptors. Kaplan-Meier estimation and
      multivariate analysis of disease-free and overall survival rate corroborated the
      importance of p53 as a prognostic parameter. CONCLUSION: Overexpression of p53
      protein emerged as a reliable and independent predictor for disease recurrence
      and reduced survival rates in patients with breast cancer.

PMID- 8252481
TI  - Relationship between variant forms of estrogen receptor RNA and an apoptosis
      related RNA, TRPM-2, with survival in patients with breast cancer.
AB  - BACKGROUND: Although smaller variant forms of estrogen receptor (ER) messenger
      RNA (mRNA) have been detected in breast tumors, neither their prevalence nor
      their prognostic significance have been evaluated. Similarly, TRPM-2 mRNA, the
      product of a gene induced principally during the onset of apoptosis, is present
      in mouse and human breast cancer cell lines, but whether it also occurs in
      primary breast tumors and is related to disease outcome is unknown. METHODS: The
      relative expression and transcript size of ER mRNA and TRPM-2 mRNA in 126 primary
      breast tumors were measured by Northern analysis and compared with tumor grade,
      hormone receptor status, extent of tumor necrosis, and survival. RESULTS: In ER
      positive tumors, 64% of the tumors had only the normal 6.5 kb ER mRNA, an
      additional 9% had the normal plus smaller ER mRNA, and 2% had variant forms. Only
      8% of ER-negative tumors had ER mRNA transcripts. There were significant
      relationships between the occurrence of ER mRNA and low tumor grade, ER-positive
      receptor status, and better survival. In contrast, TRPM-2 mRNA was found in only
      17% of breast tumors, none of which could be grouped with respect to grade,
      hormone receptor status, or survival. CONCLUSIONS: The presence of smaller
      variant forms of ER mRNA either alone or in association with the normal ER
      transcript is not indicative of an unfavorable prognosis, whereas TRPM-2 mRNA
      occurs in many primary breast tumors, but has no apparent relationship to
      survival.

PMID- 8252482
TI  - The uses and limitations of DNA flow cytometry in stage IB or II cervical
      carcinoma.
AB  - BACKGROUND: The role of flow cytometry in predicting prognosis for cervical
      carcinoma remains unclear. METHODS: Flow cytometric analysis was performed on
      tissues, fixed in formaldehyde solution and embedded in paraffin, from 411
      patients with Stage IB or II cervical carcinoma who had been treated with radical
      abdominal hysterectomy and bilateral pelvic lymphadenectomy. RESULTS: DNA
      aneuploid-multiploid tumors were found in 37.5%, tetraploid in 4.6%, and diploid
      peridiploid in 57.9%. Five-year recurrence-free survival rates of the three
      groups were 74.3%, 77.8%, and 76.4%, respectively (P > 0.05). DNA aneuploidy and
      DNA index (DI) of greater than 1.3 were highly correlated to parametria
      extension. In univariate analysis, pelvic lymph node metastases, stage,
      parametrial extension, depth of cervical stromal invasion, tumor size, and DI
      (1.3, 1.4, 1.5 as breakpoint) were significant prognostic factors. DNA ploidy, S
      phase fraction, and S-G2M fraction were not significant. In multivariate
      analysis, DI of greater than 1.3, pelvic node metastases, clinical Stage II, and
      depth of stromal invasion greater than two-thirds of full cervical thickness were
      independent and significant variables. The prognostic index (PI), defined by the
      model, was able to categorize the patients into three distinct risk groups. The 5
      year recurrence free survival rates of the low-, intermediate-, and high-risk
      groups were 89.5%, 73.0%, and 58.9%, respectively (P < 0.0001). CONCLUSIONS: The
      prognostic value of the DI as a single variable is promising and warrants
      additional investigation to establish its appropriate use.

PMID- 8252483
TI  - National survey of ovarian carcinoma. Part V. The impact of physician's specialty
      on patients' survival.
AB  - BACKGROUND: Data analysis of the recent National Survey of Ovarian Carcinoma
      revealed significant differences in patterns of care among various physician
      specialists. The goal of this study was to determine if different care patterns
      led to differences in patient survival. METHODS: Data were collected from 25
      consecutive patients with ovarian cancer diagnosed in 1983 and 1988 from 1230
      hospitals with cancer programs across the United States. RESULTS: A total of
      12,316 patients from 904 hospitals were registered, of whom 20.8% were cared for
      by gynecologic oncologists (GYO), 45.0% by obstetrician-gynecologists (OBG), and
      21.1% by general surgeons (GS). GYO preferred the upper-lower midline incision in
      44.1% of patients, whereas both OBG and GS chose the low midline approach in 44
      45%. GYO performed more hysterectomies, oophorectomies, omentectomies, and lymph
      node and peritoneal biopsies than did other specialists. Although the rates of
      surgery of the small intestine were comparable between GYO and GS, the latter
      performed significantly more colostomies and resections of the large intestine.
      The optimal debulking rates were: GYO, 42-45%; OBG, 40-44%; and GS 25%. There was
      no significant survival difference between patients cared for by GYO and those
      cared for by OBG for all stage divisions. However, with the exception of patients
      with Stage I disease, patients cared for by GS had significantly reduced survival
      than did those cared for by GYO and OBG (P < 0.004). CONCLUSION: Efforts must be
      made to ensure that more patients with ovarian cancer are cared for by physicians
      in the appropriate specialties.

PMID- 8252484
TI  - Therapy of human ovarian carcinoma xenografts using doxorubicin encapsulated in
      sterically stabilized liposomes.
AB  - BACKGROUND: This study compared the therapeutic effects of doxorubicin
      hydrochloride in saline and in sterically stabilized, long-circulating liposomes
      composed of hydrogenated soy phosphatidylcholine/cholesterol/polyethylene glycol
      distearoyl-phosphatidyl-ethanolamine (Doxil). METHODS: The drug formulations were
      injected intravenously or intraperitoneally to treat the human ovarian carcinoma
      HEY, which was implanted subcutaneously or intraperitoneally into mature female
      Swiss nude mice. RESULTS: The long-circulating liposome formulation was
      significantly more effective than was the free drug in inhibiting tumor growth
      and in producing cure. The liposome formulation was significantly less toxic than
      was the free drug. This is the first demonstration of the therapeutic
      effectiveness of doxorubicin in sterically stabilized liposomes against human
      tumor xenografts. CONCLUSIONS: The encapsulation of doxorubicin in long
      circulating liposomes significantly enhanced the therapeutic efficacy of the drug
      against a human ovarian carcinoma.

PMID- 8252485
TI  - Microsurgical neck dissection for occultly metastasizing medullary thyroid
      carcinoma. Three-year results.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) metastasizes early into the
      regional lymph nodes, but distant metastases occur late. Modified radical neck
      dissection might improve the treatment results for occultly metastasizing MTC.
      METHODS: The authors report 23 patients after a minimal follow-up of 2 years
      (median, 36 months). There were 11 female and 12 male patients. The mean age was
      43 years (+/- 13 years). The surgical technique included the meticulous
      dissection of all compartments of the neck, resulting in a unilateral or
      bilateral modified radical neck dissection with the complete removal of the
      lymphatic and fatty tissue between important anatomical structures. The surgical
      boundaries extended cranially to the mastoid, caudally to the brachiocephalic
      vein involving a transcervical mediastinal dissection, and laterally to the edge
      of the trapezoid muscle. Ten patients were treated bilaterally and 13 patients
      unilaterally. RESULTS: The basal calcitonin values of 18 of the 23 patients were
      postoperatively normalized with 4 patients having normal basal and pentagastrin
      stimulated calcitonin levels. Five patients with persistently elevated basal
      serum calcitonin values had a marked reduction of the postoperative calcitonin
      levels compared with their preoperative concentrations. However, in these five
      patients histologic abnormalities precluded a surgical cure. The permanent
      complication rates were tolerable (4 of 33 neck dissections). CONCLUSIONS: The
      microsurgically extended neck dissection can reduce basal and pentagastrin
      stimulated serum calcitonin values to normal levels even after long intervals
      following primary thyroidectomy.

PMID- 8252486
TI  - Rearrangement of bcl-2 genes in malignant lymphomas in Chinese patients.
AB  - BACKGROUND: Only a small percentage of Asian patients with non-Hodgkin lymphoma
      may have follicular type disease. According to molecular analysis done recently,
      the incidence of rearrangement of bcl-2 gene in patients with follicular lymphoma
      was lower in Japan than in the United States, suggesting possible geographic or
      racial differences between Asian and Western populations. The current study was
      undertaken to obtain data from Taiwan to compare with data from Japan, Hong Kong,
      and Western countries. METHODS: Using probes of genomic 5' bcl-2, major
      breakpoint region (mbr) and minor breakpoint cluster region (mcr) for the
      breakpoint cluster region of the bcl-2 gene, genomic DNA samples from 55 patients
      with B-cell lymphoma (17 with follicular type and 38 with diffuse type) were
      analyzed by Southern blot analysis. RESULTS: Eleven patients had bcl-2 gene
      rearrangement, including 9 of 17 (52.9%) patients with follicular lymphoma and 2
      of 38 (5.3%) patients with diffuse B-cell lymphoma. Nine patients had the
      breakpoint located within the mbr, one at both the mbr and the 5' bcl-2 regions,
      and the other had bcl-2 translocation with involvement of the mcr. DNA fragment
      of bcl-2 was found to comigrate with JH genes in all patients with follicular
      lymphoma and diffuse lymphoma who had bcl-2 rearrangement at mbr. The remaining
      patient who had bcl-2 translocation at mcr had no comigration with JH, Jk, or C
      lambda genes. CONCLUSIONS: Despite the low incidence of follicular lymphoma in
      Chinese patients, the incidence of bcl-2 gene involvement was higher in patients
      from Taiwan than in those from Japan and Hong Kong, but similar to the incidence
      of those from Western countries.

PMID- 8252487
TI  - Massive cisplatin overdose by accidental substitution for carboplatin. Toxicity
      and management.
AB  - BACKGROUND: Unlike the related drug carboplatin, cisplatin is highly nephrotoxic
      and must be given with vigorous intravenous hydration at a much lower dose. As
      the result of an accidental substitution of cisplatin for carboplatin, a 68-year
      old woman received a massive overdose of cisplatin without intravenous hydration.
      METHODS: Laboratory documentation included measurements of platinum
      concentrations by atomic absorption spectroscopy and of xeroderma pigmentosum
      group E (XPE) binding factor, a protein that is involved in the recognition step
      of DNA repair. RESULTS: Toxicities included severe emesis, myelosuppression,
      renal failure, and deafness, which are well known. Other toxicities were
      seizures, hallucinations, loss of vision, and hepatic toxicity, which were
      unusual and may have been caused by the magnitude of the overdose. As late as day
      19, there was a continued cellular response from cisplatin, as evidenced by
      decreased levels of XPE binding factor in extracts from the patient's peripheral
      blood lymphocytes. Plasmapheresis was effective in lowering the platinum
      concentration from greater than 2900 ng/ml to 200 ng/ml and appeared to be of
      clinical benefit. Even after the onset of renal failure, hydration to increase
      urine volume resulted in increased urinary excretion of platinum. Granulocyte
      macrophage colony-stimulating factor (GM-CSF) was used to ameliorate
      myelosuppression. The patient received a transplanted kidney from her monozygotic
      twin sister and survived with no clinically significant deficit except for
      deafness. CONCLUSION: No previous reports exist of survival after such a high
      dose of cisplatin without intravenous hydration. In the future, patients may
      benefit from similar management and heightened awareness of the possibility of
      accidental substitution.

PMID- 8252488
TI  - The effect of dietary protein depletion on hepatic 5-fluorouracil metabolism.
AB  - BACKGROUND: Protein calorie malnutrition, which is highly prevalent in tumor
      bearing hosts, increases toxicity to 5-fluorouracil (5-FU), but the mechanisms
      are unclear. This study investigated the effects of protein depletion on 5-FU in
      vivo hepatic metabolism using F19-nuclear magnetic resonance spectroscopy (19F
      NMRS). METHODS: Rats received normal (21.5%) or low (2.5%) protein diet for 25
      days. 5-FU was injected intraperitoneally, and hepatic fluorine spectra were
      obtained. Parallel experiments were conducted to determine serum 5-FU
      pharmacokinetics using high-performance liquid chromatography (HPLC) and to
      measure hepatic dihydropyrimidine dehydrogenase (DPD) activity. RESULTS: The mean
      time of initial detection of fluoro-beta-alanine and the mean duration of the 5
      FU signal in the liver were significantly prolonged in the low-protein group. 5
      FU clearance and hepatic DPD activity were significantly lower in the low-protein
      group. Low-protein animals demonstrated increased toxicity, with diarrhea, weight
      loss, leukopenia (P < 0.001), and an 85% mortality, compared with regular diet
      animals, who had mild diarrhea and weight loss but no leukopenia and a 12%
      mortality. CONCLUSION: Protein depletion results in increased toxicity to 5-FU,
      which is associated with a significantly decreased rate of hepatic metabolism and
      clearance of 5-FU and a significant decrease in hepatic DPD activity. 19F-NMRS
      can noninvasively identify these alterations of 5-FU metabolism in vivo and may
      serve as a useful guide to determining chemotherapy dosage adjustments to reduce
      toxicity.

PMID- 8252489
TI  - Acute promyelocytic leukemia with t(15;17) abnormality after chemotherapy
      containing etoposide for Langerhans cell histiocytosis.
AB  - BACKGROUND: Epipodophyllotoxins, etoposide and teniposide, have been shown to be
      implicated in the development, of acute myelogenous leukemia in patients treated
      for solid tumors or acute lymphoblastic leukemia. Etoposide has been shown to be
      an effective agent against Langerhans cell histiocytosis (LCH) and has gained
      wider use recently for first-line and salvage chemotherapy in cases of systemic
      LCH. METHODS: The authors report two patients with secondary acute promyelocytic
      leukemia (APL) with a t(15;17) abnormality after chemotherapy that included
      etoposide for the treatment of LCH. RESULTS: Patient 1, a 6-year-old girl, had
      APL develop 11 months after cessation of therapy that included vinblastine,
      prednisolone, and etoposide (9600 mg/m2 in total dose) for LCH. Patient 2, a 3
      year-old girl, had APL develop 9 months after cessation of therapy that included
      vincristine, methotrexate, prednisolone, cyclophosphamide (10,800 mg/m2), and
      etoposide (4800 mg/m2) for LCH. CONCLUSIONS: The authors have experience with
      four patients treated with etoposide for LCH and suggest that there is a
      predisposition to secondary APL with t(15;17) for patients with LCH treated with
      etoposide. The authors warn against the imprudent use of etoposide as a first
      line therapy for LCH.

PMID- 8252490
TI  - Neonatal benign sacrococcygeal teratoma may recur in adulthood and give rise to
      malignancy.
AB  - BACKGROUND: The capacity of neonatal sacrococcygeal teratomas (SCT) to recur is a
      well-recognized phenomenon. However, only a few studies have reported recurrence
      of the tumors beyond childhood. METHODS: A follow-up of patients for the
      detection of late recurrent SCT was performed in 45 patients, ages 4-43 years
      (mean, 21.5 years). All of the patients had been operated on in infancy for a
      benign SCT. RESULTS: Three adults with persistent or recurrent SCT were found.
      The recurrent tumors were diagnosed 21-43 years after the initial diagnosis and
      operative treatment. Two recurrences were histologically benign, and one was
      malignant. In the patient with the malignant recurrence, the coccyx was not
      removed primarily. The malignant recurrence was a mucinous adenocarcinoma and
      probably originated from a preexisting benign epithelial component of the
      teratoma. CONCLUSIONS: The capacity of a benign SCT to recur may be retained into
      adulthood. Follow-up of patients after operation for a SCT, even when the tumor
      is benign, should extend far beyond infancy. Abdominal radiographs may help
      detect late recurrent tumors with intrapelvic calcifications. When any recurrence
      is found, malignancy should be suspected.

PMID- 8252491
TI  - Infrequency of ras, p53, WT1, or RB gene alterations in Wilms tumors.
AB  - BACKGROUND: Alteration of the ras family of oncogenes and of the tumor suppressor
      genes p53 and RB are the most common genetic events in human tumors. Although
      there have been no reports of the prevalence of these alterations in Wilms
      tumors, overexpression of the N-myc and insulin-like growth factor-II (IGF-II)
      genes have been observed, and alteration of another tumor suppressor gene (WT1)
      has been demonstrated. METHODS: Forty-four Wilms tumor specimens were tested for
      the presence of N-, K-, and H-ras mutations in codons 12, 13, and 61 by single
      strand conformation polymorphism (SSCP) analysis and direct DNA sequence
      analysis. Sixteen tumors were tested for abnormalities of WT1 by Southern and
      northern blot analysis and reverse transcriptase polymerase chain reaction (RT
      PCR). N-myc, c-myc, WT1, and IGF-II mRNA expression was measured in 16 tumors by
      Northern blot analysis. Thirty-eight tumors were screened for p53 mutations by
      SSCP analysis and direct DNA sequence analysis. Nine tumors were analyzed for
      loss of heterozygosity (LOH) of RB. RESULTS: Although the authors confirmed that
      N-myc and IGF-II are overexpressed in Wilms tumors, no mutations of ras family,
      p53, or RB genes were identified, and no gross alterations of WT1 were detected
      by Southern or Northern blot analysis. CONCLUSIONS: These findings suggest that H
      ras, K-ras, N-ras, p53, and RB are not involved in the pathogenesis of Wilms
      tumor.

PMID- 8252492
TI  - Orchiectomy versus goserelin and flutamide in the treatment of newly diagnosed
      metastatic prostate cancer. Analysis of the criteria of evaluation used in the
      European Organization for Research and Treatment of Cancer--Genitourinary Group
      Study 30853.
AB  - This European Organization for Research and Treatment of Cancer (EORTC) trial
      30853 is the fifth EORTC--Genitourinary Group randomized phase III trial of
      endocrine treatment for patients with newly diagnosed metastatic prostate cancer.
      Special attention was given to the assessment of response and/or progression.
      Each of the following factors was assessed separately as nonspecific and
      subjective criteria of response or progression: performance status, pain,
      alkaline and acid phosphatase, hemoglobin, urinary symptoms, and prostate
      specific antigen (PSA). Objective progression was based on measurable disease.
      The observed sequence of progression was: (1) protein-specific antigen; (2) bone;
      (3) pain; and (4) performance status. Protein-specific antigen, an optional
      parameter, was the first sign of progression in more than 50% of patients whose
      disease had progressed.

PMID- 8252493
TI  - Is disease flare a problem?
AB  - When given for the first time to previously untreated patients with advanced
      prostate cancer, luteinizing hormone-releasing hormone (LHRH) analogs induce a
      transient rise in pituitary luteinizing hormone levels. As a consequence of this
      increase of LH, there is, within the first 2 to 3 days, a surge of testosterone,
      which can cause an exacerbation of the symptoms. First reports concerning this
      flare have been anecdotal, and in most studies, flare is reported with an
      incidence of 4-33%. This variance is due mainly to the confusion about the
      definition of the flare phenomenon. No distinctions have been made between
      clinical flare, with its manifestations of subjective or objective aggravation of
      cancer related symptoms, and the biochemical flare that results of the LHRH
      analog administration and that occurs in a majority of patients and is
      characterized by increases in testosterone, prostatic acid phosphatase, and
      prostate specific antigen. As the possible interference of the flare phenomenon
      on the ultimate aftermath of the patient's response to therapy is not yet known,
      it seems mandatory that flare prevention should be carried out whenever LHRH
      analogs are prescribed in monotherapy.

PMID- 8252494
TI  - Quality of life in prostatic cancer patients.
AB  - As a first effort to introduce quality-of-life assessment in prostatic cancer
      clinical trials, the European Organization for Research and Treatment of Cancer
      Genitourinary Group, in cooperation with European Organization for Research and
      Treatment Quality of Life Group, initiated protocol 30853, coordinated by Louis
      Denis. This protocol compared the efficacy of treatment with orchiectomy alone to
      that with Zoladex (Zeneca Pharmaceuticals, Alderley Macclesfield, Cheshire, UK)
      plus flutamide in previously untreated patients with metastatic cancer. The use
      of patient-administered quality-of-life questionnaires was optional, and of 327
      patients, only 22% had pretreatment assessments. This trial revealed many
      clinician's considerable reluctance to perform quality of life research, partly
      because of feasibility problems and partly because of doctors' doubts about the
      value of such efforts. Psychologic distress, fatigue, issues of social and family
      life, and pain were found to be the most important concerns on a subjective
      basis, and this finding was confirmed by objective parameters. There was a
      discrepancy between doctors' evaluations and patients' opinions about subjective
      morbidity, namely sexual status and pain. Quality of life assessment should
      become a mandatory part of clinical trials in prostate cancer.

PMID- 8252495
TI  - Is there a best castration?
AB  - Androgen ablation by bilateral orchidectomy has long been considered the gold
      standard against which other forms of treatment for the management of advanced
      prostate cancer can be evaluated. It now is recognized that the use of
      luteinizing hormone-releasing hormone analogs provides a form of primary
      endocrine therapy that is as effective as surgical castration for the treatment
      of disseminated disease.

PMID- 8252496
TI  - Cyproterone acetate--mechanism of action and clinical effectiveness in prostate
      cancer treatment.

PMID- 8252497
TI  - Mechanism of action and pure antiandrogenic properties of flutamide.
AB  - Although treatment of intact adult male rats with the pure antiandrogen flutamide
      or a luteinizing hormone-releasing hormone (LHRH) agonist alone leads to partial
      inhibition of ventral prostate weight, maximal inhibition is achieved by
      combination of the two drugs. Potentializing effects of the two compounds were
      observed even on prostatic ornithine decarboxylase activity. Because LHRH
      agonists are widely used to achieve medical castration in men treated for
      prostate cancer, it is of interest to observe that in the dog, known for being
      the best model for studies of the action of LHRH agonists, flutamide does not
      interfere with the potent desensitizing action of the LHRH agonist on pituitary
      LH secretion, thus supporting the combined use of flutamide with an LHRH agonist
      for maximal androgen blockade without loss of efficiency of the LHRH agonist.
      Because prostate cancer is known to show a high degree of heterogeneity of its
      sensitivity to androgens, we analyzed the effect of combined antiandrogen therapy
      on parameters more sensitive to androgens than ventral prostatic weight itself.
      In agreement with its pure antiandrogenic characteristics, flutamide alone has no
      stimulatory effect on the intraprostatic level of mRNA encoding the C1 or C3
      component of prostatic binding protein (PBP), whereas cyproterone acetate (CPA),
      megestrol acetate (MEG), and, especially, medroxyprogesterone acetate (MPA)
      markedly stimulate PBP-C1 and PBP-C3 mRNA levels, an effect reversed by
      flutamide, thus further supporting the intrinsic androgenic activity of all these
      steroidal derivatives. Similar androgenic effects of the steroidal derivatives
      were observed on prostatic ornithine decarboxylase activity. Androgen-sensitive
      Shionogi tumor cells were then used to assess the antiandrogenic/androgenic
      properties of flutamide and the above-indicated steroidal derivatives. MPA, MEG,
      CPA as well as spironolactone-stimulated cell proliferation under both in vivo
      and in vitro conditions, thus illustrating the intrinsic androgenic activity of
      all these compounds. Flutamide was inactive by itself and reversed the
      stimulatory effect of all other compounds, thus indicating its pure
      antiandrogenic activity. Although castration reduces intraprostatic
      dihydrotestosterone (DHT) to undetectable levels in the rat and guinea pig, the
      concentration remains at about 50% of the value found in intact men after
      castration, thus indicating an important contribution of the adrenals to DHT in
      the human prostate, a finding that requires the addition of an antiandrogen to
      block the action of this important amount of DHT remaining after castration.

PMID- 8252498
TI  - Pharmacology of nilutamide.

PMID- 8252499
TI  - Some statistical considerations for the interpretation of trials of combined
      androgen therapy.
AB  - Since 1989, there have been strongly conflicting opinions regarding the validity
      of the proposition that an antiandrogen added to standard hormonal therapy could
      improve the outcome in patients with newly diagnosed metastatic prostate cancer.
      To some degree, these conflicting opinions arose from misinterpretations of a
      number of "negative" clinical trials. The misinterpretations happened because
      these "negative" trials had insufficient statistical power to refute the reported
      "positive trial", and information illustrating their statistical power was absent
      from their reports. Thus, readers were not given the necessary information to
      distinguish between negative and inconclusive results. In addition, many of the
      negative reports were early analyses of ongoing clinical trials, a practice that
      always should be avoided. This article reviews and illustrates the statistical
      principles that are applicable to the interpretation of low-powered negative
      clinical trials and discusses the design and conduct of clinical trials.

PMID- 8252500
TI  - Comparability of prostate trials.
AB  - The present overview of advanced prostate cancer required the identification of
      randomized clinical trials studying the question of maximal androgen blockade
      versus the classic castration therapy. The heterogeneity of the trials concerned
      the type of castration (surgical or chemical) and the type of antiandrogen
      (flutamide, Anandron, or cyproterone acetate) added to castration. This paper
      reviews the different types of heterogeneity that might exist among trials that
      are involved in the overview: study design, randomization procedure, treatment
      evaluation, statistical evaluation, and data maturity. In order to overcome these
      various types of heterogeneity and to compare like with like, the treatment
      comparison should be stratified a posteriori by question (i.e., type of
      castration or type of anti-androgen studied) and by study. In this way, one may
      draw valid conclusions. Of course, those trials with a larger number of patients
      and a longer follow-up will contribute more to the overview's results.

PMID- 8252501
TI  - Systematic overview (metaanalysis) of all randomized trials of treatment of
      prostate cancer.

PMID- 8252502
TI  - Long-term results of Danish Prostatic Cancer Group trial 86. Goserelin acetate
      plus flutamide versus orchiectomy in advanced prostate cancer.
AB  - In a multicenter trial conducted by the Danish Prostatic Cancer Group, 264
      patients with advanced prostate cancer were randomized either to undergo
      bilateral orchiectomy or to receive combination treatment with goserelin acetate
      and flutamide. This report is an update of that study, covering a median follow
      up for survival of 57 months. Of 262 patients who were evaluated, 208 have died.
      As noted in earlier analyses of this study, no differences in time to progression
      and cause-specific and overall survival could be identified between the two
      treatment groups. In conclusion, the combination of goserelin and flutamide was
      not clinically superior to bilateral orchiectomy in the treatment of advanced
      prostate cancer.

PMID- 8252503
TI  - A further analysis of European Organization for Research and Treatment of Cancer
      protocol 30805. Orchidectomy versus orchidectomy plus cyproterone acetate versus
      low-dose diethylstilbestrol.

PMID- 8252504
TI  - Short-term versus long-term addition of cyproterone acetate to buserelin therapy
      in comparison with orchidectomy in the treatment of metastatic prostate cancer.
      European Organization for Research and Treatment of Cancer--Genitourinary Group.
AB  - In an open, multicenter, three-armed, randomized study, we compared the effects
      of short-term (2 weeks) and continuous addition of the antiandrogen cyproterone
      acetate to the luteinizing hormone-releasing hormone agonist buserelin to those
      of orchidectomy in patients with advanced prostate cancer. No significant
      differences among the three treatment arms with respect to response rate,
      subjective response, time-to-progression, overall survival, and cancer deaths
      were observed. It was concluded that the short-term or continuous addition of
      cyproterone acetate to buserelin administered intranasally did not improve
      treatment results compared to orchidectomy only.

PMID- 8252505
TI  - Orchidectomy versus goserelin plus flutamide in patients with metastatic prostate
      cancer (EORTC 30853). European Organization for Research and Treatment of Cancer-
      Genitourinary Group.
AB  - A total of 327 patients with metastatic prostate cancer were randomized to
      receive bilateral orchiectomy or treatment with Zoladex and flutamide. The trial
      aimed to evaluate subjective and objective time to progression, survival, and
      incidence and duration of response. Strict quality control and evaluation by
      independent ad hoc committees were organized. Progression was assessed for each
      of 13 parameters. The time to subjective and objective progression was in favor
      of the combination treatment, with statistical significances of P = 0.009 and P =
      0.008, respectively. This delay in objective progression resulted in increased
      survival in favor of the combination treatment for death by cancer (P = 0.02) or
      overall survival (P = 0.05). Survival differences were more marked in the
      patients with better prognostic factors. The clinical significance of these
      differences for the individual patient requires detailed assessment.

PMID- 8252506
TI  - The use of flutamide in hormone-refractory metastatic prostate cancer.
AB  - In a recent intergroup study under the auspices of the National Cancer Institute,
      603 eligible patients with newly diagnosed disseminated adenocarcinoma of the
      prostate were prospectively randomized in a double-blinded clinical trial to
      receive either a gonadotropin-releasing hormone analogue (leuprolide) and a
      nonsteroidal antiandrogen (flutamide) or leuprolide and placebo. Of the 603
      eligible patients, 300 were in the leuprolide and placebo arm and 303 were in the
      leuprolide and flutamide arm. At the time of disease progression, the code was
      broken: Those patients in the placebo arm were given the opportunity to receive
      flutamide, and the patients in the flutamide arm were treated at their
      physician's discretion. There was no survival time distribution difference, based
      on survival measured from the progression data, between the patients who were
      received flutamide after progression and those who were treated at their
      physician's discretion after progression. Furthermore, the addition of flutamide
      to leuprolide at the time of disease progression resulted in a survival-time
      distribution that is similar to other treatments of hormone-refractory prostate
      cancer.

PMID- 8252507
TI  - Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or
      placebo as treatment of metastatic prostate cancer. Anandron International Study
      Group.
AB  - The efficacy of total androgen blockade using orchiectomy and nilutamide was
      compared with orchiectomy with placebo in a large double-blind clinical trial
      with 457 patients. The median interval to objective progression was 20.8 months
      for total androgen blockade and 14.7 months for orchiectomy alone (P = 0.0041).
      The median interval to death for all patients was 37.1 months versus 29.8 months
      (P = 0.041). Decrease in pain was seen at months 1, 3, and 6 in a significant
      percentage for the total androgen blockade group. A significant difference in
      prostate specific antigen levels was seen at months 3 and 6, with normalization
      of 75% and 28%, respectively, in both groups at both times. The tolerance of the
      nonsteroidal antiandrogen nilutamide showed visual disturbances as a side-effect,
      resulting in the withdrawal of five patients from treatment. Liver and lung
      disturbances were transient. Total androgen blockade is a more effective
      treatment for metastatic prostate cancer than orchiectomy alone in this study
      population.

PMID- 8252508
TI  - Multicenter randomized trial comparing Zoladex with Zoladex plus flutamide in the
      treatment of advanced prostate cancer. Survival update. International Prostate
      Cancer Study Group.

PMID- 8252509
TI  - Combination treatment in M1 prostate cancer.
AB  - The treatment of advanced prostate cancer is based on hormone manipulation to
      eliminate the trophic effect of testosterone on sensitive androgen tissue of the
      tumor. In this study, we evaluated the efficacy of the partial androgen blockage
      versus the complete androgen blockage. One hundred, twenty-two patients were
      entered in this study and randomly were treated with buserelin alone or with
      buserelin and flutamide. The group that received buserelin was given cyproterone
      acetate (200 mg/day) during first 3 weeks of treatment to avoid "flare-up".
      During the follow-up (range 0-244 +/- 1 weeks), we evaluated 59 patients (61.4%)
      that had positive response and 37 patients (38.6%) that showed progressive
      disease: There were no statistically significant differences between the two
      treatment groups, not even in the evaluation of median time to response and of
      median time to treatment failure. In conclusion, the results emphasize that total
      androgenic blockage is as effective as a luteinizing hormone-releasing hormone
      analog used alone.

PMID- 8252510
TI  - Anandron (nilutamide) combined with orchiectomy in stage D prostate cancer
      patients. Overview of seven randomized placebo controlled studies.

PMID- 8252511
TI  - Overview of phase III trials on combined androgen treatment in patients with
      metastatic prostate cancer.

PMID- 8252512
TI  - Long-term results after ventriculoatrial shunting in children.
AB  - A consecutive series of 120 patients with infantile hydrocephalus who were
      subjected to ventriculoatrial shunting was studied. The average length of follow
      up was 11 years. Operative mortality was zero. Seven patients died during the
      follow-up period; in all cases but one of these the cause of death was not a
      consequence of a shunt-related procedure. The incidences of infection and slit
      ventricle syndrome were 4.2% and 1.8% respectively. Two hundred and fifty-three
      shunt revisions were performed, yielding a revision rate of 2.2 per patient. Of
      these 253 revisions 167 (66%) were elective lengthening of the atrial catheter.
      The number of reoperations for adjusting the length of the atrial catheter of for
      revision of the distal end of the shunting system is a major disadvantage of
      ventriculoatrial shunting which actually speaks in favor of ventriculoperitoneal
      shunting as the primary procedure for the treatment of pediatric hydrocephalus.

PMID- 8252513
TI  - Pontine gliomas causing locked-in syndrome.
AB  - The terminal phase of pontine glioma is reportedly characterized by disturbance
      of consciousness. The authors retrospectively reviewed 8 children who died of
      pontine gliomas in their hospitals. The hospital records were analyzed
      specifically in regard to neurological status and terminal case. All children
      became mute and quadriplegic with cranial nerve palsies. The oldest child, 17
      years in age, unquestionably showed the classical locked-in syndrome for the last
      4 months. Six of the remaining 7 (average 5 years of age), while labeled as
      semicomatose, responded to calling by blinking and/or vertical eyeball movement.
      The authors consider that they were indeed awake in the locked-in state until
      very near death. This would raise a serious ethical problem of whether or not
      they should be intubated and kept ventilator-dependent at the time of respiratory
      failure, which often occurs.

PMID- 8252514
TI  - Central nervous system tumors in Mexican children.
AB  - Five hundred and seventy primary central nervous system (CNS) tumors from the
      Department of Pathology at the National Institute of Pediatrics in Mexico City,
      collected from 1970 to 1989, were histologically reclassified in order to find
      out their relative incidence as well as their outstanding features. With this, we
      could establish a frame of reference for our local population, contributing to
      the epidemiological analysis of these entities. All the tumors were examined
      independently by two pathologists (C.R. and M.R.), using the classification of
      Rorke et al. Histological type, patient age and sex, and tumor location were
      analyzed. CNS tumors were the secondmost frequently encountered solid tumors,
      after lymphomas, and were increasing in incidence at a rate of 2.2 annually.
      Children in the age group 0-9 years were most often affected, and there was a
      predominance of male patients. Astrocytoma and medulloblastoma were the most
      common tumor types. The infratentorial region was the most frequent tumor
      location in the 2- to 9-year age group. By contrast, in the under 2-year-olds a
      supratentorial location was more frequent, and the incidence of germ cell tumors
      was proportionally high. In general, some histological types seemed to be
      associated with particular age groups. Although we found primitive
      neuroectodermal tumors to be the fifth most common at all ages (except for
      medulloblastoma), many other authors do not report a similar finding.

PMID- 8252515
TI  - Histochemistry with Helix pomatia agglutinin in human germ cell tumors: detection
      of nongerminomatous components and correlation between HPA reactivity and
      radiosensitivity in germinomas.
AB  - Binding sites of Helix pomatia agglutinin (HPA) were examined in 32 patients with
      intracranial human germ cell tumors. HPA reactivity was found in vascular
      endothelial cells and erythrocytes of patients with blood type A or AB. HPA
      positive neoplastic cells were seen in one yolk sac carcinoma in a patient with
      blood group A, and in embryonal carcinomas and teratomas irrespective of blood
      group type. Although in 10 out of 18 germinomas neoplastic cells were totally
      negative for HPA, another 8 germinomas showed HPA-positive neoplastic cells which
      were distributed sporadically or in an area and independent of blood group types.
      HPA-negative germinoma patients showed a very good response to radiotherapy,
      whereas 4 out of 8 HPA-positive tumors showed poor radiosensitivity, with a
      residual lesion seen on computed tomography even after the total radiation dose
      of 40-50 Gy. These findings suggest that HPA-positive neoplastic cells in
      germinomas indicate components of differentiation of non-germinomatous germ
      cells. HPA-positive germinomas might be less radiosensitive than HPA-negative
      germinomas.

PMID- 8252516
TI  - Anti-epileptic therapy and behaviour disturbances in children.
AB  - In order to evaluate the effects on behaviour of some anti-epileptic drugs, we
      studied 300 children treated with phenobarbital and other drugs; their age ranged
      from 3.1 months to 15.9 years. The children were divided into two groups: group
      A: 197 (116 male and 81 female) children, mean age +/- SD 5.3 +/- 2.8 years,
      treated with phenobarbital; group B: 103 (66 male and 37 female) children, mean
      age 6.4 +/- 3.1 years, treated with anti-epileptic drugs other than
      phenobarbital. In all patients hyperactivity, irritability, disturbances of
      sleep, and drowsiness were investigated. The parents of patients completed a
      questionnaire with seven items. In group A, 150 (76.1%) children showed one or
      more behaviour disturbances, while in Group B a smaller number of patients 32
      (31%) had such disorders. There was a significant difference between the two
      groups (P < 0.0001). The most frequent disorder was hyperactivity. The results of
      this study suggest that anti-epileptic drugs, in particular phenobarbital, can
      cause behaviour disturbances.

PMID- 8252517
TI  - Indicators of hypoxia in cerebrospinal fluid of hydrocephalic children with
      suspected shunt malfunction.
AB  - We used high performance liquid chromatography to determine the concentration of
      purine metabolites in the cerebrospinal fluid of three hydrocephalic children
      with a history of shunt malfunction. Hypoxanthine and xanthine levels were high
      in comparison with controls. We consider these purines to be valuable indicators
      of disturbance of neuronal metabolism following the sustained rise in
      intracranial pressure caused by shunt valve malfunction.

PMID- 8252518
TI  - Meningomyelocele associated with cranium bifidum: rare coexistence of two major
      malformations.
AB  - Three cases of lumbosacral meningomyelocele associated with cranium bifidum are
      reported. The meningomyeloceles were of the neural placode type and the cranium
      bifidum was an interfrontal encephalomeningocele in all cases. Two of the
      patients received ventriculoperitoneal shunts and had evidence of type II Chiari
      malformation on magnetic resonance imaging. No evidence of a Chiari malformation
      was revealed in the third patient. We discuss the etiology of the rare
      coexistence of these two major malformations.

PMID- 8252519
TI  - Subarachnoid fluid collection in infants complicated by subdural hematoma.
AB  - In the natural history of infantile extracerebral fluid collections, subarachnoid
      fluid collection itself is regarded as a benign lesion, and surgical treatment is
      not indicated. As this condition is age-related and self-limiting, spontaneous
      resolution can be expected in most cases by 2-3 years of age. However, out of 20
      cases of infantile subarachnoid fluid collection in an 8-year period, 3 infants
      developed subdural hematoma. Infantile subarachnoid fluid collection seems to be
      prone to complicate subdural hematoma. Surgical treatment should be considered
      when subarachnoid fluid collection is complicated by subdural hematoma due to
      arachnoid ruptures or tearing of the bridging veins. Therefore, all patients
      should be observed closely and measures should be taken to prevent head trauma
      since it may precipitate subdural hematoma.

PMID- 8252520
TI  - Spondylolysis and spondylolisthesis after five-level lumbosacral laminectomy for
      selective posterior rhizotomy in cerebral palsy.
AB  - Of 163 children who have undergone five-level lumbosacral laminectomies for
      selective posterior rhizotomy, 20% of those re-X-rayed post-operatively (19/99)
      have developed incidental isthmic spondylolysis or grade I spondylolisthesis. The
      majority of patients were ambulatory, active, spastic diplegics. There were five
      children with isthmic defects at L3-4, three at L4-5 and 11 at L5-S1. Six of the
      19 children had grade I spondylolisthesis, but none were symptomatic nor has
      there been any evidence of further slipping to date. It is postulated that the
      laminectomy, associated lordosis and increased mobility after rhizotomy may be
      factors in the causation.

PMID- 8252521
TI  - Apert's syndrome.
AB  - This paper discusses 33 cases of Apert's syndrome which were treated in the
      Australian Craniofacial unit at the adelaide Children's Hospital. The main
      features were discussed. We found that mild ventricular dilatation is common in
      Apert's syndrome but without associated raised intracranial pressure. Severe
      ventricular dilatation was seen in only one case. No shunt procedures were
      performed. We also studied the changes in the ventricular size after transcranial
      corrective procedures. There was no significant change in the ventricular size,
      the increase in the skull volume was compensated by expansion of the brain tissue
      and to some extent by increase in the subarachnoid space. Two cases with unusual
      features are also described.

PMID- 8252522
TI  - Giant craniopharyngioma with blindness reversed by surgery.
AB  - A 3-year-old boy presented with a 3-day history of total blindness. There were no
      features of raised intracranial pressure or endocrine disturbance. Magnetic
      resonance imaging of the brain showed a giant craniopharyngioma measuring 5 x 3
      cm. It was located in the suprasellar region and produced a mass effect with
      compression of the III and both lateral ventricles. The tumour extended downwards
      into the pituitary fossa. Urgent surgical decompression and subtotal excision of
      the tumour resulted in complete visual recovery in the right eye. The left eye
      remained blind. The blindness might have been caused by direct pressure on the
      optic nerves and chiasma by the tumour. The lack of visual recovery in the left
      eye may be the consequence of additional ischaemic insult to the left optic
      nerve. It is concluded that surgical decompression should be carried out in a
      patient with a giant craniopharyngioma presenting with total blindness before the
      condition is considered hopeless.

PMID- 8252523
TI  - Intracranial mesenchymal chondrosarcoma: a case report and literature review.
AB  - Intracranial mesenchymal chondrosarcoma is a rare entity. The case of a 13-year
      old girl with mesenchymal chondrosarcoma which seemed to arise from the dura
      mater is presented here together with a review of the literature. In the present
      case, the tumor involved the superior sagittal sinus. It recurred 21 months after
      gross total removal of the mass and coagulation of the involved wall of the
      superior sagittal sinus. Reoperation was performed followed by radiation therapy.

PMID- 8252524
TI  - Delayed brain hemorrhage associated with prophylactic whole brain irradiation for
      pediatric malignant brain tumor: a case report.
AB  - Intraparenchymal hemorrhage in the left frontal lobe suddenly occurred in a 7
      year-old girl who had undergone partial removal of an undifferentiated brain stem
      glioma and received craniospinal (30 Gy) and posterior fossa booster (20 Gy)
      irradiation at the age of 20 months. The brain hemorrhage was thought to be
      delayed irradiation effect. Follow-up neuro-imaging at age 9 years showed two
      more small occult chronic and subacute hemorrhages in the brain. The possibility
      of repeated hemorrhage as a delayed reaction to brain irradiation is emphasized.

PMID- 8252525
TI  - A probably familial saccular aneurysm of the anterior communicating artery in a
      neonate.
AB  - A 32-day-old boy died of recurring cerebral hemorrhages starting on the 4th day
      of life. Autopsy disclosed a remittingly ruptured saccular aneurysm of the
      anterior communicating artery. A 7-day-old brother of his had previously died of
      recurring subarachnoid hemorrhages as well. The young age of the patient, the
      site of the aneurysm, and its probably familial occurrence make this case a
      unique one. Nonaneurysmatic basal cerebral arteries showed remarkable
      histological changes partly resembling those seen in fibromuscular dysplasia,
      some of them probably representing preaneurysmatic alterations. A known
      underlying systemic disease could not be found, and immunohistochemical detection
      of type III collagen revealed no identifiable deficiency.

PMID- 8252526
TI  - Giant meningioma of the III ventricle in a child: case report and review of the
      literature.
AB  - We report the case of an 11-year-old girl with a giant meningioma of the III
      ventricle who presented with signs and symptoms of raised intracranial pressure.
      The tumor was removed through a transcallosal approach. A review of current
      literature yielded 16 previous cases of meningiomas of the III ventricle in the
      pediatric age group. The usual form of presentation is that of a midline syndrome
      with no localizing signs. In the cases that were operated on, surgical
      intervention was rewarding and mortality was low. A very unusual finding in the
      meningioma that we report was its origin in the floor of the III ventricle, a
      circumstance that has only once been described previously.

PMID- 8252527
TI  - Synthesis of a terminal A-B-C disaccharide fragment of flambamycin, curamycin,
      and avilamycin.
AB  - Methyl 2,6-dideoxy-4-O-[2,6-dideoxy-4-O-(3,5-dichloro-4-hydroxy-2-methoxy-6-
      methylbenzoyl)-beta-D-arabino-hexopyranosyl]-alpha-D-arabino-he xopyranoside (25)
      corresponds to an A-B-C disaccharide subunit of the title antibiotics. It was
      synthesized from suitably protected monosaccharide and aromatic precursors. The
      readily available 4,6-O-benzylidene-1,2-O-(R)-propylidene-alpha-D-glucopyranose
      was converted in six steps into 2-O-acetyl-4-O-benzoyl-3-O-benzyl-6-deoxy-alpha-D
      glucopyranosyl bromide, which was condensed with methyl 3-O-benzyl-2,6-dideoxy
      alpha-D-arabino-hexopyranoside in the presence of mercury(II) cyanide. Methyl 4-O
      (2-O-acetyl-4-O-benzoyl-3-O-benzyl-6-deoxy-beta- D-glucopyranosyl)-3-O-benzyl-2,6
      dideoxy-alpha-D-arabino-hexopyranosi de was converted either into methyl 2,6
      dideoxy-4-O-(6-deoxy-beta-D- glucopyranosyl)-alpha-D-arabino-hexopyranoside by
      removal of the protective groups or into methyl 3-O-benzyl-4-O-(3-O-benzyl-2,6
      dideoxy-beta-D-arabino-hexopyranosyl)-2,6 - dideoxy-alpha-D-arabino
      hexopyranoside (22) by selective deacetylation, Barton deoxygenation, and Zemplen
      debenzoylation. Disaccharide 22 was deprotonated with butyllithium and treated
      with 4-benzyloxy-3,5-dichloro-2-methoxy-6-methylbenzoyl chloride to give the
      title compound 25 after hydrogenolysis.

PMID- 8252528
TI  - Regioselective synthesis and characterization of naphthylethylcarbamoyl-beta
      cyclodextrins.
AB  - Regioselective reactions of 1-(1-naphthyl)ethyl isocyanate (NEIC) with beta
      cyclodextrin (beta-CD) were studied with and without NaH activation of beta-CD in
      N,N-dimethylformamide (DMF) and pyridine. All six possible monosubstituted CD
      products were separated and characterized by proton NMR. Primary substitution
      product predominates when the reaction was carried out under reflux condition in
      pyridine without NaH activation. The C-2 substitution product predominates when
      the reaction was carried out in DMF. Conversion of 2-O-(1-(1
      naphthyl)ethylcarbamoyl)-beta-CD to 6-O-(1-(1-naphthyl)ethylcarbamoyl)-beta-CD
      was observed when NaH was used to activate hydroxyl groups of CD.

PMID- 8252529
TI  - Synthesis and utilization of saccharide intermediates.
AB  - A new method has been developed for preparation of partially pivaloylated
      saccharides in one step from readily available starting materials. These
      intermediates were used in the synthesis of disaccharides and a glucosteroid.

PMID- 8252530
TI  - Synthesis and antineoplastic properties of 3'-deoxy-3'-fluoroketonucleoside
      derivatives. Correlations between structure and biological activity.
AB  - Three fluoroketonucleosides (6, 8, and 11) have been synthesized by direct
      oxidation of the fluoro precursors. The presence of the highly electronegative
      fluorine atom in the alpha position to the carbonyl group favours hydration
      leading to the gem-diol form so that the beta-elimination process to afford 6 and
      8 was made difficult and failed in the case of the difluoro compound 11. The
      biological activity of compounds 6, 8, and 11 was tested on human peripherical
      blood lymphocytes stimulated by PHA, and on RAJI and DAUDI cells. The IC50 values
      showed that, surprisingly, the 3'-enopyranosyl-2'-uloses 6 and 8 have much better
      antineoplastic activities than their 2'-enopyranosyl-4'-ulose analogues 14 and 15
      obtained previously. Moreover, compound 11, which is difluorinated at C-3' and C
      6' but does not have a C = C-C = O group in its structure, is also very active.
      These results emphasize the important biological role played by the fluorine atom
      in this family of compounds and suggest a peculiar mechanism of action which is
      until now unspecified.

PMID- 8252531
TI  - The conformation of the monomethyl ethers of methyl beta-lactoside in D2O and
      Me2SO-d6 solutions.
AB  - The solution conformations of all the possible monomethyl ethers of methyl beta
      lactoside have been analysed using molecular mechanics and dynamics calculations
      and nuclear magnetic resonance data (variable temperature and NOE experiments).
      The overall shape of all the compounds studied is fairly similar and may be
      described by conformers included in a low-energy region with phi = -100 +/- 40
      degrees and psi = -135 +/- 35 degrees, which is ca. 5% of the total potential
      energy surface for the glycosidic linkages of the disaccharides.

PMID- 8252532
TI  - Structural analysis of sialic acid-containing carbohydrates by the reductive
      cleavage method.
AB  - The applicability of the reductive-cleavage method to the structural analysis of
      sialic acid-containing carbohydrates was investigated using fully methylated
      methyl alpha- and beta-N-acetylneuraminic acid (1 and 2, respectively). Both
      compounds were fully stable to reductive cleavage in the presence of borane
      dimethylsulfide and boron trifluoride etherate but were slowly degraded in the
      presence of triethylsilane and promoters such as trimethylsilyl
      trifluoromethanesulfonate, boron trifluoride etherate, or a mixture of
      trimethylsilyl methanesulfonate and boron trifluoride etherate. However, after
      selective reduction of the ester groups of 1 and 2 with sodium borohydride, the
      products (3 and 4, respectively) underwent rapid reductive cleavage to yield the
      expected anhydroalditols, which were characterized as their acetates (8 and 11)
      by GLC-MS. The major product was also characterized as its benzoate (9) by 1H NMR
      spectroscopy. The usefulness of this analytical method was demonstrated using 3'
      sialyllactose, i.e., alpha-Neu5Ac-(2-->3)-beta-D-Galp-(1-->4)-D-Glc. The
      methylated and ester-reduced trisaccharide (13) was reductively cleaved with
      Me2S.BH3-BF3.ET2O and the products were acetylated. Analysis by GLC-MS revealed
      the products expected from terminal (nonreducing) Neu5Ac (8 and 11), 3-linked
      Galp (16), and 4-linked Glcp (15) residues in relative molar ratios of
      1.2:1.0:1.0, respectively. However, direct reductive cleavage of the fully
      methylated trisaccharide (12) yielded the fully methylated disaccharide
      anhydroalditol derivative alpha-Neu5Ac-(2-->3)-1,5An-D-Gal (14) and the product
      (15) derived from 4-linked Glcp residues. These experiments therefore established
      both the composition and the sequence of the trisaccharide.

PMID- 8252533
TI  - Structural characterization of feruloyl oligosaccharides from spinach-leaf cell
      walls.
AB  - Hydrolysis of spinach-leaf cell walls with Driselase (a fungal enzyme
      preparation) released two arabino-oligosaccharides and one galactobiose, each
      carrying a ferulic acid moiety. The oligosaccharides were characterized by NMR
      spectroscopy, methylation analysis, and FABMS. They were O-(2-O-trans-feruloyl
      alpha-L-arabinofuranosyl)-(1-->5)-L-arabinof uranose, O-(6-O-trans-feruloyl-beta
      D-galactopyranosyl)-(1-->4)-D-galactopy ranose, and O-alpha-L-arabinofuranosyl-(1
      ->3)-O-(2-O-trans-feruloyl-alpha-L-a rabino- furanosyl)-(1-->5)-L
      arabinofuranose.

PMID- 8252534
TI  - Escherichia coli serotype K45 capsular antigen: a glycan containing 3-acetamido
      3,6-dideoxygalactopyranose.
AB  - The primary structure of the acidic capsular antigen of Escherichia coli
      O8:K45:H9 was shown by glycose analysis, methylation analysis, and one- and two
      dimensional 1H and 13C NMR spectroscopy to be composed of repeating branched
      tetrasaccharide units having the structure: [formula: see text] The
      polysaccharide contains the uncommon amino sugar 3-acetamido-3,6-dideoxy-D-
      galactopyranose, which has not been previously identified in a capsular antigen.

PMID- 8252535
TI  - Klebsiella K43 capsular polysaccharide: primary structure and depolymerisation by
      a viral-borne endoglycanase.
AB  - The capsular polysaccharide of Klebsiella K43 has been studied by glycose
      analysis, methylation analysis, and NMR spectroscopy, and by bacteriophage
      depolymerisation of the native polysaccharide. Additional evidence for the
      structure of the repeating unit came from base-catalysed degradation of the
      methylated polysaccharide, and from NMR spectroscopic analysis of the lithium
      degraded polysaccharide and of the oligosaccharide-alditol derived from the
      repeating unit oligosaccharide obtained from a bacteriophage degradation. The
      polysaccharide was shown to have the repeating unit: [formula: see text]

PMID- 8252536
TI  - Ultrastructural evidence for intramolecular double stranding in iota-carrageenan.
AB  - Kinetic studies of primary processes of conformational ordering in gel-forming
      biopolymers have suggested that a change in mechanism from intermolecular to
      intramolecular multistrand formation occurs on lowering the concentration of
      biopolymer. We report here ultrastructural observations consistent with
      intramolecular double stranding in a carbohydrate polymer, iota-carrageenan, by
      arresting this process of primary conformational ordering by an ultra-rapid
      freeze fixation technique. High-resolution transmission electron microscopy (TEM)
      revealed isolated iota-carrageenan chains showing a range of morphologies
      (linear, circular, and hairpin) consistent with intramolecular stranding. Control
      experiments in which iota-carrageenan was frozen in the disordered form revealed
      longer and thinner strands.

PMID- 8252537
TI  - Preparation and characterization of four new variously deacetylated
      lysogangliosides, breakdown products of GM1.
AB  - Four new deacylated lysogangliosides were obtained through alkaline hydrolysis of
      either C18 or C20 sphingosine homologues of GM1. By this procedure, both the
      fatty acids residue and the N-acetyl group of sialic acid were removed to give
      mono-N-acetyl-lysoGM1 (C18 and C20); the additional loss of the N-acetyl group of
      the acetylgalactosamine moiety gave de-N-acetyl-lysoGM1 (C18 and C20) with three
      free amino groups. The structures of four deacetylated lysogangliosides were
      unambiguously characterized by chemical analysis and 1H and 13C NMR spectroscopy
      as well as by negative ion FABMS. The aim of this study was to isolate pure
      breakdown products of gangliosides, enabling the evaluation of the mechanism of
      action of glycosphingolipids through their cleavage and identification of
      structures of potential pharmacological activity. These new substances were
      prepared as candidates to influence eicosanoid production and the mechanisms
      dependent on protein kinase C and phospholipase A2.

PMID- 8252538
TI  - The analysis of agarose by the reductive cleavage method.
AB  - Agarose was structurally characterised by permethylation and subsequent reductive
      cleavage. Treatment of the fully methylated polysaccharide with triethylsilane
      and a mixture of trimethylsilyl methanesulfonate and boron trifluoride etherate
      followed by a newly developed, acid-catalysed, in situ acetylation yielded two
      main products: the expected 4-O-acetyl-1,5:3,6-dianhydro-2-O-methyl-L-galactitol
      and 3-O-acetyl-1,5-anhydro-2,4,6-tri-O-methyl-D-galactitol in the molar ratio
      1:1, and traces of 1,5-anhydro-2,3,4,6-tetra-O-methyl-D-galactitol. Reductive
      cleavage using triethylsilane and trimethylsilyl trifluoromethanesulfonate as the
      catalyst yielded the same anhydroalditols as well as a smaller amount of 1,4,5
      tri-O-acetyl-3,6-anhydro-2-O-methyl-L-galactitol due to ring-opening of 3,6
      anhydrogalactopyranosyl residues during reductive cleavage. In this paper,
      results from reductive cleavage are compared with results using standard
      methylation analysis.

PMID- 8252539
TI  - Structural analysis of tamarind seed xyloglucan oligosaccharides using beta
      galactosidase digestion and spectroscopic methods.
AB  - The borohydride-reduced forms (oligoglycosyl alditols) of two isomeric
      octasaccharides (Glc4Xyl3Gal) that are released from xyloglucans of various plant
      species upon treatment with a fungal endo-(1-->4)-beta-glucanase were isolated
      and structurally characterized. A mixture of oligosaccharides that is released
      from tamarind seed xyloglucan by the endo-(1-->4)-beta- glucanase was digested
      with a commercially available beta-galactosidase (Aspergillus niger). The beta
      galactosidase selectively hydrolyzed the galactosyl residue of one of the two
      isomeric octasaccharides present in the mixture. A homogeneous preparation of the
      beta-galactosidase-resistant octasaccharide was prepared by high-resolution gel
      permeation chromatography of the enzyme-digestion products. Spectroscopic
      characterization of the oligoglycosyl alditol prepared by reduction of this
      octasaccharide confirmed the previously proposed structure that had been based on
      analysis of the mixture of isomeric octasaccharides. The availability of large
      amounts of the pure, reduced octasaccharide and of a pure, reduced
      pentasaccharide (Glc3Xyl2) made it possible to completely assign their 1H and 13C
      NMR spectra. In addition, the borohydride-reduced form of the beta-D
      galactosidase-susceptible octasaccharide isomer was purified by high pH anion
      exchange chromatography of the endo-(1-->4)-beta-glucanase-released
      octasaccharides from rape-seed xyloglucan (no beta-galactosidase treatment), and
      its 1H and 13C NMR spectra were assigned. Additional correlations between
      specific structural features of xyloglucan oligoglycosyl alditols and the
      positions of specific resonances in their NMR spectra were deduced and added to
      the extensive list that we have compiled. The effects of recording the NMR
      spectra of the xyloglucan oligoglycosyl alditols in the presence of borate salts,
      which could lead to incorrect structural assignments, are also described.

PMID- 8252540
TI  - Progressive dissociation of pectin.
AB  - The structural organization of alkaline soluble peach pectin was investigated
      over size ranges extending from micrometers to tenths of nanometers. Analysis was
      by electron microscopy and high-performance anion-exchange chromatography
      (HPAEC). Superimposed and individual circular microgels in the micrometer size
      range were isolated from mesocarp tissue of cell walls and visualized by rotary
      shadowing. Dilute NaCl and 50% aqueous glycerol disaggregated these microgels
      into rods, segmented rods, and kinked rods, which collectively comprised the
      internal gel network of the microgels. Image analysis of the shadowed specimens
      before and after disaggregation followed by curve fitting of the smoothed
      distributions revealed a multimodal distribution of lengths. HPAEC revealed that
      the multimodal aggregates were stable for the most part to further dissociation
      by increasing ionic strength.

PMID- 8252541
TI  - Enzymatic synthesis of some O-beta-D-digalactosyl glycopeptides, using beta-D
      galactosidase.
AB  - Disaccharide-peptide conjugates were obtained in yields of 30-50% from o
      nitrophenyl beta-D-galactopyranoside by employing beta-D-galactosidase from E.
      coli as catalyst. Two series of beta-D-galactosyldipeptides were examined as
      galactosyl acceptors. They both contain an L-serine residue beta-linked to the
      anomeric carbon of galactose. In the first series, serine is in the N-terminal
      position of the dipeptide; in the second series, serine is in the C-terminal
      position. The second amino acid is L-alanine or glycine. Some of our substrates
      gave a high yield of beta-(1-->3)-digalactosyldipeptide derivatives and all gave
      very little of the beta-(1-->6) regioisomer. The conditions and the limitations
      of the transgalactosylation reaction are discussed.

PMID- 8252542
TI  - Accumulation of pentamannose oligosaccharides in human mononuclear leukocytes by
      action of swainsonine, an inhibitor of glycoprotein processing.
AB  - Swainsonine, a known inhibitor of the alpha-mannosidase II involved in processing
      of asparagine-linked glycoproteins, causes accumulation of hybrid-type
      oligosaccharide-containing glycoproteins in mammalian cells. Swainsonine augments
      lymphokine-activated, killer-cell induction at suboptimal doses of interleukin-2;
      the amount needed to increase LAK activity is 100-1000 fold higher than required
      to completely inhibit mannosidase II. Human mononuclear lymphocytes, when treated
      with these relatively high (58 microM) concentrations of swainsonine showed a 3-4
      fold increase in D-[3H]mannose incorporation into the glycan as compared to
      glycans of untreated cells. Analysis indicated accumulation of high-mannose type,
      free oligosaccharides in the soluble fractions of the cell. Chromatographic
      analysis of glycan obtained by D-[2-3H]mannose labeling of human mononuclear
      lymphocytes showed synthesis of a new oligosaccharide, at 58 microM of
      swainsonine, that contained 36% of the total radioactivity incorporated into the
      glycan (oligosaccharide pool). This oligosaccharide fraction was resistant to
      hydrolysis by endoglycosidase H, endoglycosidase F, O and N-glycanase, but was
      susceptible to cleavage by Jack bean alpha-mannosidase and was bound > 90% to
      concanavalin A-Sepharose. A similar chromatographic elution profile was obtained
      from glycans labeled with D-[2-3H]mannose from mouse B16F10 melanoma and baby
      hamster kidney cells subsequent to swainsonine treatment. Methylation analysis of
      free oligosaccharides obtained from MNL revealed the presence of a pentamannose.
      These results indicate the accumulation of a free high-mannose oligosaccharide
      rather than expected hybrid-type structure on treatment of cells with relatively
      high concentrations of swainsonine.

PMID- 8252543
TI  - The regioselective tert-butyldimethylsilylation of the 6'-hydroxyl group of
      lactose derivatives via their dibutylstannylene acetals.

PMID- 8252544
TI  - Crystal and molecular structures of beta-cellobiosylnitromethane and of beta
      maltosylnitromethane heptaacetate.
AB  - The structures of the title compounds have been determined by X-ray
      crystallography, using direct methods, and have been refined to conventional
      final residual factors of R = 0.063 and R = 0.046, respectively.

PMID- 8252545
TI  - Synthesis of 3-O-(iodoethyl)-D-glucose, a stable iodo derivative of D-glucose for
      medical imaging.

PMID- 8252546
TI  - Synthesis of benzylated cycloisomaltotetraose.

PMID- 8252547
TI  - The conformations of cyclic (1-->2)-beta-D-glucans: application of
      multidimensional clustering analysis to conformational data sets obtained by
      Metropolis Monte Carlo calculations.
AB  - Sets containing up to 1.3 x 10(6) energetically accessible conformations of
      linear (1-->2)-beta-D-glucan oligosaccharides were obtained by Metropolis Monte
      Carlo (MMC) calculations performed with the GEGOP (GEometry of GlycOProteins)
      program. Quantitative analyses of the data sets (which were expressed in terms of
      the glycosidic dihedral angle coordinates) were obtained by two different
      clustering methods: (i) the three-distance hierarchical clustering method (3-DM),
      published by Jure Zupan, and (ii) a nonhierarchical clustering method (Population
      Density Projection, PDP) which, through a segmentation analysis of two
      dimensional projections of the population-density surface, establishes a
      partitioning of conformational space into a set of "cluster regions", followed by
      a clustering step where each conformation of the data set is assigned to one of
      these regions. Computer programs (MCLUST and PDPCLUST) were developed to perform
      the 3-DM and PDP analyses, respectively. The two types of analysis provided very
      similar sets of conformational families (clusters), which could be expressed as
      combinations of distinct conformations of the glycosidic torsional angles (phi,
      psi) centered at (50 degrees, 10 degrees) for conformation A, (40 degrees, 160
      degrees) for conformation B, (55 degrees, -160 degrees) for conformation B', and
      (170 degrees, 10 degrees) for conformation C. The analysis provided the
      populations of the families, along with relative rates for transitions between
      families. Examination of the frequencies of the A, B, and C glycosidic bond
      conformations with respect to their relative positions in the sequence revealed
      the tendency of the (1-->2)-beta-D-glucan to adopt conformational repeating
      structures of the general form [AnB], where n = 3 or 6. These repeating
      structures combine in an energetically cooperative fashion to give low-energy
      cyclic conformations having, for example C5 symmetry [AAAB]5 for the eicosamer,
      and C3 symmetry [AAAAAAB]3 for the heneicosamer.

PMID- 8252548
TI  - 1,2-Di-O-acetyl-5-O-benzoyl-3-deoxy-3-fluoro-D-xylofuranose. A versatile
      precursor for the synthesis of 3-deoxy-3-fluoro-beta-D-xylofuranosyl nucleosides
      as potential antiviral agents.

PMID- 8252549
TI  - Synthesis of brain-targeted 1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-(E)-5-(2
      iodovinyl)uracil coupled to a dihydropyridine <---> pyridinium salt redox
      chemical-delivery system.
AB  - 1-(2-Deoxy-2-fluoro-beta-D-ribofuranosyl-(E)-5-(2-iodovinyl)uracil (IVFRU) was
      coupled to a dihydropyridine <---> pyridinium salt redox chemical-delivery system
      (CDS) via a cleavable sugar-ester linkage as a site-directed approach to increase
      diffusion of the parent nucleoside into the central nervous system. Treatment of
      1-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)uracil with Bu(t)Me(2)SiCl in the
      presence of imidazole in DMF yielded the protected 5-O-tert-butyldimethylsilyl
      derivative. Subsequent reaction with nicotinoyl chloride hydrochloride in
      pyridine afforded 1-[5-O-tert-butyldimethylsilyl-2-deoxy-2-fluoro-3-O-(3
      pyridylcarbony  l )-beta-D-ribofuranosyl]uracil. Reaction with iodine
      monochloride in methanol simultaneously cleaved the silyl ether moiety and
      iodinated the uracil ring at the 5-position. Coupling with (E)-Bu(3)Sn-CH = CH
      SiMe(3) in the presence of (Ph3P)2Pd2(II)Cl2 in THF gave 1-[2-deoxy-2-fluoro-3-O
      (3-pyridylcarbonyl)-beta-D-ribofuranosyl]- (E)-5-(2-trimethylsilylvinyl)uracil.
      Quaternization with iodomethane in acetone yielded the N-methylpyridinium iodide
      salt. Ionation of the reactive (E)-trimethylsilylvinyl moiety with iodine
      monochloride in acetonitrile and reduction of the quaternary pyridinium iodide
      salt with sodium dithionite in the presence of sodium hydrogen carbonate was
      carried out as a one-pot procedure to afford 1-[2-deoxy-2-fluoro-3-O-(1-methyl
      1,4-dihydropyridyl-3-carbonyl)-b eta-D-ribofuranosyl]-(E)-5-(2-iodovinyl)uracil
      (IVFRU-CDS). This synthetic strategy is readily amenable to the high specific
      activity radioiodination of IVFRU.

PMID- 8252550
TI  - Synthesis of 3'- and 4'-deoxyfluorolactose and its Me3SiCH2CH2 and ceramide
      derivatives.
AB  - (2-Trimethylsilyl)ethyl (Me3SiCH2CH2)3'- and 4'-deoxyfluorolactosides (1 and 3)
      were synthesized by glycosylation of Me3SiCH2CH2 2,3,6-tri-O-benzyl-beta-D
      glucopyranoside with 2,4,6-tri-O-acetyl-3-deoxy-3-fluoro-beta-D-galactopyranosyl
      bromide and 2,3,6-tri-O-benzyl-4-deoxy-4-fluoro-beta-D-galactopyranosyl bromide.
      Anomeric deblocking of the fully acetyled Me3SiCH2CH2 glycosides (12 and 13) gave
      the corresponding hemiacetals 14 and 15. Removal of the acetyl groups gave 3'-
      and 4'-deoxyfluorolactose (2 and 4). The deoxyfluorolactosylceramides 5 and 6
      were synthesized via boron trifluoride etherate- or silver triflate-activation of
      the trichloroacetimidates prepared from 14 and 15. Silver triflate-mediated
      glycosylations showed lower reaction rates, and fewer byproducts were formed.

PMID- 8252551
TI  - A facile enzymatic synthesis of cellooligosaccharide derivatives using beta
      lactosyl fluoride.
AB  - A convenient method for the preparation of cellooligosaccharide derivatives has
      been developed that uses beta-lactosyl fluoride as the glycosyl donor. The
      reaction consists of the following enzymatic processes; (1) a cellulase-catalyzed
      regio- and stereo-selective lactosylation of a beta-cellobioside as the glycosyl
      acceptor, utilizing the transglycosylating ability of an enzyme-substrate complex
      formed from beta-lactosyl fluoride and cellulase; (2) beta-D-galactosidase
      catalyzed regioselective cleavage of the terminal D-galactose unit from the
      lactosylated product, giving rise to a beta-cellotrioside derivative. A
      cellotetraoside derivative has successfully been prepared in a stereo- and regio
      selective manner by repeating these enzymatic reactions and using the resulting
      beta-cellotrioside as starting material.

PMID- 8252552
TI  - The synthesis of 2,3-dideoxy-2-fluoro-3-C-methylpentose-containing nucleosides
      via [3,3]-sigmatropic rearrangements.
AB  - [3,3]-Sigmatropic rearrangement of in situ-formed [O,O]-silyl ketene acetals of
      butenyl fluoroacetates was used as the key step in the synthesis of racemic 2,3
      dideoxy-2-fluoro-3-C-methylpentofuranoses. The product pentofuranoses were
      transformed further into pyrimidine and purine nucleosides. The conformations of
      the synthetic carbohydrates were confirmed by single-crystal X-ray diffraction
      studies and indicated that previous structural assignments made by NMR were in
      error.

PMID- 8252553
TI  - Recognition of synthetic deoxy and deoxyfluoro analogs of the acceptor alpha-L
      Fuc p-(1-->2)-beta-D-Gal p-OR by the blood-group A and B gene-specified
      glycosyltransferases.
AB  - The disaccharide alpha-L-Fuc p-(1-->2)-beta-D-Gal p-O-(CH2)7CH3 (6), is an
      acceptor for both glycosyltransferases responsible for the biosynthesis of the A
      and B blood-group antigens. These enzymes transfer GalNAc and Gal, respectively,
      with an alpha-linkage to OH-3 of the Gal residue in 6. All six possible deoxy and
      deoxyfluoro analogs of 6, with modifications on the target Gal residue, were
      chemically synthesized and kinetically evaluated as both substrates and
      inhibitors for the A and B glycosyltransferases. Both enzymes will tolerate
      replacement of the hydroxyl groups at the 3 and 6 positions of the Gal residue.
      Substitution of OH-4 of the Gal residue, however, abolishes recognition by these
      glycosyltransferases. The 6-deoxy and 6-fluoro compounds are substrates for both
      enzymes while the 3-deoxy and 3-fluoro compounds are competitive inhibitors, with
      Ki values in the range 14-110 microM. Kinetic constants have been determined for
      the 6-deoxy and 6-fluoro derivatives.

PMID- 8252555
TI  - Study on fluorination-toxicity relationships. Syntheses of 1-N-[(2R,3R)- and
      (2R,3S)-4-amino-3-fluoro-2-hydroxybutanoyl] derivatives of kanamycins.
AB  - (2R,3R)- And (2R,3S)-4-azido-3-fluoro-2-hydroxybutanoic acids (11 and 22) have
      been prepared from 3-deoxy-3-fluoro-1,2-O-isopropylidene-alpha-D-glucofuranose
      (1) and 3,5-di-O-benzyl-1,2-O-isopropylidene-alpha-D-xylofuranose (12),
      respectively. They were then coupled to the N2N-1 group of suitably protected
      kanamycin A or kanamycin B analogs to give, 1-N-[(2R,3R)- and (2R,3S)-4-amino-3
      fluoro-2-hydroxybutanoyl]kanamycins (32-35). This group of compounds (32-34)
      exhibited similar antibacterial activity and toxicity level as those of the
      corresponding 1-N-[(S)-4-amino-2-hydroxybutanoyl] (AHB) derivatives of
      kanamycins. The base strength of the H2N-4"' group of 32 and 34, as determined by
      13C NMR spectroscopy (in D2O) at varying pD values, was found to be lower when
      compared to the basicity for the corresponding AHB analogs. The relationship
      between observed toxicity and base strength of the H2N-4"' group is discussed.

PMID- 8252554
TI  - A new method of anomeric protection and activation based on the conversion of
      glycosyl azides into glycosyl fluorides.
AB  - Glycosyl azides provide reliable anomeric protection stable to conditions for
      hydrolytic removal of ester groups, for reductive opening or release of acetalic
      diol protection, for the introduction of ether-type protection, and for
      glycosylation processes. The utility of this anomeric protection is further
      enhanced as glycosyl azides may be converted into glycosyl fluorides, which can
      be activated for glycosylation reactions. To this end, glycosyl azides have been
      subjected to 1,3-dipolar cycloaddition with di-tert-butyl acetylenedicarboxylate.
      On treatment with hydrogen fluoride-pyridine complex the N-glycosyl triazole
      derivatives directly give glycosyl fluorides.

PMID- 8252556
TI  - Syntheses of 2-deoxy-2-fluoro mono- and oligo-saccharide glycosides from glycals
      and evaluation as glycosidase inhibitors.
AB  - Several fluorinated oligosaccharides, including 2-deoxy-2-fluoro derivatives of
      cellobiose, maltose, and maltotriose were synthesized by the action of fluorine
      or acetyl hypofluorite on the corresponding glycal peracetates. Temperature
      effects on the stereoselectivities of these reactions were examined. Addition of
      acetyl hypofluorite to several 2-substituted glycals in the gluco or galacto
      series gave 2,2-disubstituted arabino- or lyxo-hexose derivatives; 3,4,6-tri-O
      acetyl-2-fluoro-D-glucal or the analogous galactal yielded 2-deoxy-2,2-difluoro
      arabino- or lyxo-hexose peracetates, whereas 2-acetoxy-3,4,6-tri-O-acetyl-D
      glucal or the analogous galactal gave 2(R)-2-acetoxy-2-fluoro-arabino- or lyxo
      hexose peracetates, respectively. 2-Acetamido-3,4,6-tri-O-acetyl-D-glucal gave
      2(R)-2-acetamido-2-acetoxy-3,4,6-tri-O-acetyl-alpha-D-arabino-hexopyrano syl
      fluoride. 2,4-Dinitrophenyl 2-deoxy-2-fluoro-beta-cellobioside was an inactivator
      of the exoglucanase from Cellulomonas fimi while 2-deoxy-2-fluoro-alpha-maltosyl
      and alpha-maltotriosyl fluorides were slow substrates of human pancreatic alpha
      amylase and rabbit muscle glycogen debranching enzyme, respectively.

PMID- 8252557
TI  - Synthesis of thiazole-4-carboxamide-adenine difluoromethylenediphosphonates
      substituted with fluorine at C-2' of the adenosine.
AB  - Synthesis of an analogue 3 of thiazole-4-carboxamide adenine-dinucleotide (TAD)
      in which the beta-oxygen atom of the pyrophosphate bridge is replaced by a
      difluoromethylene group has been achieved. Likewise, 2'-deoxy-2'-fluoroadenosine
      containing analogues of TAD (4) and its difluoromethylenediphosphonate congener
      (5) have been synthesized. Adenosine 5'-difluoromethylenediphosphonate (8) was
      prepared from 5'-O-tosyladenosine (6) and tris(tetra-n
      butylammonium)difluoromethylenediphosphonate (7) by a modified procedure of
      Poulter's. Compound 8 was converted into the 2',3'-cyclic carbonate 9 by
      treatment with triethyl orthoformate. Treatment of 9 with 2',3'-O
      isopropylidenetiazofurin (10) in pyridine in the presence of DCC gave a mixture
      of dinucleotide 11 and the isopropylidene-protected diadenosine tetraphosphonate
      12. After deprotection of 11, the desired beta-difluoromethylene TAD (3) was
      separated by HPLC as the minor product. The diadenosine tetraphosphonate 12, an
      analogue of Ap4A, was obtained as the major component. Alternatively, 2',3'-O
      isopropylidenetiazofurin (10) was tosylated, and the product 13 was further
      converted into the corresponding difluoromethylenediphosphonate 14 by coupling
      with 7. DCC-catalyzed coupling of 14 with 2'-deoxy-2'-fluoroadenosine (15)
      followed by deisopropylidenation afforded the analogue 5. Again the corresponding
      tetraphosphonate analogue of tiazofurin 17 was the predominant product.
      Dinucleotide 4 was obtained by coupling of the carbonyldiimidazole-activated
      tiazofurin 5'-monophosphate with 2'-deoxy-2'-fluoroadenosine 5'-monophosphate. 2'
      Deoxy-2'-fluoroadenosine (15) was prepared efficiently from the known N6-benzoyl
      3'-O-tetrahydropyranyladenosine (18), which was converted into 3'-O
      tetrahydropyranyl-2'-O-triflyl-5'-O-trityladenosine (20) by tritylation and
      triflation. Treatment of 20 with sodium acetate in hexamethylphosphoric triamide,
      followed by deacetylation afforded 9-(3-O-tetrahydropyranyl-5-O-trityl-beta-D-
      arabinofuranosyl)-N6-benzoyladenine (22), which was then treated with DAST. After
      deprotection of the product, 15 was obtained in good yield.

PMID- 8252558
TI  - Congenital heart disease in adolescents and adults. Natural and postoperative
      history across age groups.
AB  - Advances in the diagnosis and treatment of heart disease have significantly
      affected survival patterns. Many adults with these anomalies have never had
      cardiac surgery because they have not required operation, their lesions are
      treatable in adulthood, or they are inoperable. A large number have reached adult
      life after undergoing cardiovascular surgery in infancy and childhood. Generally,
      results in these patients are gratifying, but cure is seldom achieved, and many
      have important sequelae and residua.

PMID- 8252559
TI  - Congenital heart disease in adolescents and adults. Teratology, genetics, and
      recurrence risks.
AB  - This brief review has described historic highlights of etiologic knowledge,
      current concepts in the categorization of cardiovascular anomalies based upon
      ongoing advances in teratology, and epidemiologic evaluations of biologic and
      xenobiotic risk factors with emphasis on the teratogenic roles of maternal
      diabetes, hyperphenylalaninemia, and parental exposures to alcohol, drugs,
      solvents, pesticides, lead, and other toxic substances. Evidence is presented for
      a strong genetic basis of cardiovascular maldevelopment requiring further studies
      to define at-risk families. Counseling and personal and societal preventive
      interventions may reduce the occurrence of some forms of CHD.

PMID- 8252560
TI  - Interventional catheter procedures used in congenital heart disease.
AB  - Many of the transcatheter devices described in this article remain
      investigational in the United States. Currently, we consider the applications of
      these techniques as either (1) procedures of choice (for closures of patent
      ductus arteriosus, balloon dilation or stent implantation for peripheral
      pulmonary stenoses, balloon dilation of recurrent or persistent aortic
      coarctation, balloon pulmonary valvotomy, closure of congenital muscular or
      postoperative residual ventricular septal defects, closure of patent foramen
      ovale in the setting of cyanosis, balloon aortic valvotomy, fenestration
      closures, coil embolization of thoracic collateral vessels); (2) effective
      alternatives to surgical therapy (closures of atrial septal defects of the
      secundum type, balloon dilation of native aortic coarctation, stent implantation
      for conduit or baffle obstruction, device emobolization of paravalvular leaks or
      coronary artery fistulas); or (3) treatments with unproven effect (closure of
      acute postmyocardial infarction ventricular septal defects, closure of patent
      foramen ovale for idiopathic stroke, stent implantation for pulmonary venous
      stenosis) (Table 1). Patients with congenital heart disease often undergo
      multiple catheterizations and surgical therapies, each with its own complications
      and sequelae. Clinical trials of catheter-based technologies for patients with
      congenital heart disease have consisted of uncontrolled case series with a lack
      of standardized follow-up. Additional prospective large-scale clinical trials of
      these therapies seem necessary before their widespread acceptance.

PMID- 8252561
TI  - Infective endocarditis in the adult with congenital heart disease.
AB  - Advances in the diagnosis and therapy of congenital heart disease in the past few
      decades have allowed the survival of young adults who are a fertile substrate for
      developing bacterial endocarditis. In addition to valvular involvement, young
      adults with congenital disease may develop infection on the ventricular septum,
      or in a vascular shunt, a patent ductus arteriosus, or coarctation of the aorta.
      The incidence of endocarditis in children and adults with congenital heart
      disease is higher than with rheumatic heart disease or mitral valve prolapse.
      Infecting organisms, diagnosis, and therapy are similar to acquired heart
      disease, but the physiologic variations and patient population often add a unique
      flavor to the management of this group.

PMID- 8252562
TI  - Acyanotic congenital heart disease. Atrial and ventricular septal defects,
      atrioventricular canal, patent ductus arteriosus, pulmonic stenosis.
AB  - This article discusses the four common congenital heart lesions associated with
      communications between the systemic circulation and the pulmonary circulation, as
      well as valvular pulmonic stenosis with intact ventricular septum. The incidence
      and description of each specific anatomical malformation is presented. The
      clinical findings on physical examination, electrocardiography, chest radiograph,
      and echocardiography are delineated for each defect. Emphasis is placed on the
      medical and surgical management and the long-term outcome of such management.

PMID- 8252563
TI  - Aortic/mitral obstruction and coarctation of the aorta.
AB  - The prevalence, anatomy and physiology, clinical manifestations, laboratory
      findings, and management of patients with aortic/mitral obstruction and
      coarctation of the aorta are assessed. Subaortic stenosis reviewed includes
      discreet membranous and tunnel subaortic stenosis as well as hypertrophic
      obstructive cardiomyopathy. The discussion of valvular aortic stenosis includes
      both congenital and acquired forms of the disease. Supravalvular aortic stenosis
      is described along with coarctation of the aorta. Mitral valvular stenosis
      includes the congenital as well as acquired variety with focus on the congenital
      lesion. Current opinion regarding the medical, the cardiac catheterization,
      interventional, and the surgical approaches to therapy is presented.

PMID- 8252564
TI  - Tetralogy of Fallot and pulmonary atresia/ventricular septal defect.
AB  - Surgical repair of tetralogy of Fallot is associated with excellent results. Long
      term complications include arrhythmias, sudden death, and right ventricular
      aneurysm formation. Reoperation is necessary in approximately 5% of patients for
      residual ventricular septal defect, pulmonary regurgitation, or pulmonary
      stenosis. Pulmonary atresia/ventricular septal defect is a more complex
      situation, and the anatomy needs careful delineation by cardiac catheterization
      prior to any surgical intervention. Palliation with a shunt or first-stage repair
      may be effective, or radical repair may be considered in those with adequate
      pulmonary distribution.

PMID- 8252565
TI  - Transposition complexes.
AB  - Transposition complex refers to the reversal of the normal connection of the
      ventricles to the great arteries, and includes both complete transposition of the
      great arteries (TGA) and congenitally corrected TGA. Adults with complete TGA
      usually have had an atrial switch (Mustard or Senning), procedures now abandoned
      in many pediatric centers in favor of the arterial switch (Jatene). The course
      and treatment of patients with congenitally corrected TGA is much more variable,
      depending on which associated lesions are present. Such patients share the
      tendency to complete heart block, systemic tricuspid AV valve regurgitation, and
      systemic RV dysfunction. Information about these conditions in adults is urgently
      needed to reduce our reliance on extrapolation from the pediatric experience.

PMID- 8252566
TI  - Tricuspid atresia and univentricular heart after the Fontan procedure.
AB  - Patients undergoing the Fontan operation must be selected carefully. The best
      results are obtained in those who fulfill the criteria of Choussat et al. Other
      treatment options are now available. Patients known to be at high risk for the
      Fontan procedure should be considered for cavopulmonary anastomoses or cardiac
      transplantation. It is unknown whether performing the Fontan operation at an
      earlier age will help prevent the long-term problems with ventricular
      dysfunction. Long-term follow-up of all patients following the Fontan procedure
      is mandatory with noninvasive assessment of ventricular function and the
      anastomotic site. Arrhythmias should be managed aggressively with prompt
      restoration of sinus rhythm, when possible, ideally with antiarrhythmic agents
      with little or no negative inotropic action. Periodic assessment of serum
      proteins should be performed. Although the operative risk of the Fontan operation
      has continued to improve over the last few years, and in one series has been as
      low as 8%, long-term complications continue and reinforce the concept of the
      Fontan operation being a palliative rather than a curative procedure.

PMID- 8252567
TI  - Pulmonary vascular obstructive disease.
AB  - The history, clinical course, pathophysiology, pathology, diagnosis, and therapy
      of pulmonary vascular obstructive disease are presented. An explanation is
      provided for the terms Eisenmenger syndrome, Eisenmenger complex, and pulmonary
      vascular disease. The complications frequently seen in the natural history of the
      condition are presented, as are the therapeutic options. Despite intensive
      investigation of new therapeutic products, the most promising treatment for
      established pulmonary vascular obstructive disease remains heart-lung operation
      or single-lung transplant with repair of cardiac defects. Even with this option,
      the long-term outlook for this progressive condition remains dismal.

PMID- 8252568
TI  - Systemic complications of cyanosis in adults with congenital heart disease.
      Hematologic derangements, renal function, and urate metabolism.
AB  - The regulation of red cell mass, the hemostatic derangements, the structure and
      function of the kidneys and the determinants of plasma urate levels are important
      concerns in the clinical management of adults with cyanotic congenital heart
      disease. Because these topics are interrelated, they are discussed together in
      terms of pathogenesis, clinical expression, and management.

PMID- 8252569
TI  - Congenital heart disease in adolescents and adults. Pregnancy and contraception.
AB  - As the detection and treatment of congenital heart disease improves, more women
      are reaching childbearing age. The type of congenital heart disease, whether
      there has been corrective surgery, and the patient's functional status determines
      the maternal as well as fetal outcome. The patient may present to her physician
      for preconceptual counseling or late in her pregnancy with little care and in
      severe distress. These possible situations necessitate that the physician becomes
      familiar with congenital heart disease and its implications in the pregnant
      patient.

PMID- 8252570
TI  - Psychosocial concerns of adults with congenital heart disease. Employability and
      insurability.
AB  - Addressing the psychosocial concerns of the growing population of adults with
      congenital heart disease presents a unique challenge to health care providers.
      These patients frequently need information about their disease with emphasis on
      how it may affect their sexuality, childbearing, and risk of having children with
      congenital heart disease. These patients also face problems in securing
      employment that will provide health insurance coverage for their cardiac
      conditions.

PMID- 8252571
TI  - Training in the care of adult patients with congenital heart disease.
AB  - The growing population of patients with congenital heart lesions surviving to
      adulthood necessitates a fresh look at the clinical training required to care for
      these patients. Physicians in pediatric and medical cardiology, general
      pediatrics, general medicine, family practice, obstetrics and gynecology and
      other specialities will all have a role in the care of these patients. Most
      likely, training will need to be incorporated into existing pathways with a clear
      delineation of a body of knowledge necessary to assimilate to complete the
      training program. The authors favor a certificate of added qualification for the
      treatment and management of adults with congenital heart disease to encourage
      excellence in preparation of physicians to care for this complex patient
      population.

PMID- 8252572
TI  - Growth and hypertrophy of the heart: towards an understanding of cardiac specific
      and inducible gene expression.

PMID- 8252573
TI  - Fibroblast and transforming growth factor expression in the cardiac myocyte.

PMID- 8252574
TI  - Growth factors in endothelial regeneration.

PMID- 8252575
TI  - Proposed roles for growth factors in mediating smooth muscle proliferation in
      vascular pathologies.

PMID- 8252576
TI  - Cytokines and smooth muscle cells in atherosclerosis.
AB  - For several years it has been recognised that the common denominator for many of
      the well known risk factors for cardiovascular disease is that they all may give
      rise to chronic inflammatory reactions in vascular tissues. New tools made
      available through rapid progress in the fields of immunology and molecular
      biology have made it possible to reach a better understanding of the molecular
      events leading to the development of atherosclerosis. These developments have
      resulted in a renewed interest in the role of inflammatory and immune reactions
      in atherogenesis. During recent years it has also become increasingly clear that
      the release and ability to respond to cytokines is not restricted to the cells
      classically included in the immune system. At least in vitro, smooth muscle cells
      and endothelial cells produce and respond to cytokines in a manner suggesting
      that they play active roles in inflammatory reactions. Several cytokines have
      been found to influence the growth of smooth muscle cells, suggesting a possible
      link between two of the major characteristics of atherosclerotic lesions: the
      inflammatory reaction, and the intimal proliferation of smooth muscle cells. Of
      particular interest is the ability of interleukin-1 and TGF beta to induce
      autocrine PDGF loops in smooth muscle cells. By this mechanism a transient
      secretion of cytokines from activated leucocytes may give rise to prolonged
      activation of smooth muscle cell proliferation. However, the effects of cytokines
      on vascular cells are very complex and it cannot be taken for granted that the
      inflammatory reaction generally encountered in atherosclerotic lesions only
      serves to promote the progress of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252577
TI  - Approaches to the development of selective inhibitors of vascular smooth muscle
      cell proliferation.
AB  - Abnormal proliferation of VSMC is a feature of atheromatous plaques and is
      responsible for obstructive neointimal lesions at the sites of mechanical or
      immunological intimal damage. We have discussed approaches to the development of
      specific inhibitors of VSMC proliferation based firstly on studies of the
      mechanism of action of known inhibitors and secondly on the identification of
      genes which are unique to and necessary for VSMC proliferation. The effects of
      angiotensin converting enzyme inhibitors, heparin and hexamethylene bisacetamide
      on VSMC proliferation have been discussed. Each of these types of agent has been
      shown to inhibit VSMC proliferation in vitro and/or in vivo. Examination of the
      mechanisms by which these agents inhibit VSMC proliferation reveals that
      transforming growth factor beta is an important mediator of their action and that
      the processes of de-differentiation and proliferation are independently
      regulated. Studies aimed at identifying genes involved in VSMC proliferation are
      at an early stage but have already provided strong evidence to support the
      hypothesis that VSMC in the vessel wall are heterogeneous and contain a
      subpopulation of cells with an enhanced proliferative capacity. Identification of
      the genes expressed by these cells may allow specific inhibitors of VSMC
      proliferation to be developed and may shed light on the pathogenesis of
      neointimal lesions.

PMID- 8252578
TI  - Overview of the fibroblast growth factor and receptor families: complexity,
      functional diversity, and implications for future cardiovascular research.

PMID- 8252579
TI  - Parathyroid hormone related peptide gene expression in human fetal and adult
      heart.
AB  - OBJECTIVE: The aim was to investigate the expression of parathyroid hormone
      related peptide (PTHrP) gene in the human fetal and adult heart. METHODS:
      Molecular biological techniques were employed as well as immunocytochemistry and
      western blot analysis using rabbit polyclonal anti-PTHrP(1-34) and anti-PTHrP (56
      86) on normal human fetal and adult heart tissues. Northern blot analysis of both
      normal human fetal and adult heart total RNA, using a human full length cDNA
      probe, and polymerase chain reaction analysis of normal human fetal and adult
      heart cDNAs with exon specific oligonucleotides were carried out. RESULTS:
      Positive staining was detected with both anti-PTHrP(1-34) and anti-PTHrP(56-86)
      in fetal heart at 12 weeks of gestation. In both fetal and adult hearts, multiple
      putative PTHrP proteins were observed with apparent molecular mass of 14-125 kDa.
      Multiple hybridising PTHrP mRNA isoforms (1.4, 2.1, 3.2, and 4.5 kb) were
      detected in both fetal and adult heart total RNAs. The fetal and adult heart
      cDNAs amplified from the cDNA libraries showed the presence of the 5' non-coding
      exon II and coding exons III-IV but not the 5' non-coding exon Ic. CONCLUSIONS:
      PTHrP is expressed in normal human fetal and adult hearts suggesting that it has
      a function as an endogenous modulator of the cardiovascular system.

PMID- 8252580
TI  - Heparin does not inhibit oncogene induction in rabbit aorta following balloon
      denudation.
AB  - OBJECTIVE: Smooth muscle cell proliferation and migration are the predominant
      responses to intimal and medial injury after percutaneous transluminal coronary
      angioplasty. The in vivo inhibitory effect of heparin on these responses is well
      documented. To test the hypothesis that the antiproliferative effect of heparin
      in vivo may be related to an inhibition of proto-oncogene expression, the effects
      of pretreatment with heparin on the expression of the c-myc, c-fos and c-jun
      proto-oncogenes were examined in a rabbit model of balloon denudation. METHODS:
      Animals were randomised 5 h before balloon denudation to receive a subcutaneous
      injection of unfractionated heparin (7500 IU.kg-1, n = 7) or saline (n = 6).
      Total RNA extracted from the aorta 1 h after balloon denudation was analysed by
      northern blot technique. A histological study was also performed in saline
      treated (n = 4) and heparin treated (n = 4) animals 28 d after balloon
      denudation. RESULTS: The histological study showed that the degree of neointimal
      thickening was significantly less in heparin treated animals. However, the level
      of expression of the proto-oncogenes we studied was similar in both groups.
      CONCLUSIONS: Heparin inhibits neointimal thickening after balloon denudation.
      This inhibition is not associated with an overall decrease in the level of
      expression of the c-myc, c-fos, or c-jun proto-oncogenes in the arterial wall,
      suggesting that the antiproliferative effect of heparin may be due to an effect
      on other events in the cell cycle.

PMID- 8252581
TI  - Alterations of rabbit aortic smooth muscle cell proliferation in diabetes
      mellitus.
AB  - OBJECTIVE: Diabetes mellitus is a known risk factor for atherosclerosis. Because
      initiation and/or progression of the atherosclerotic process is associated with
      alterations in vascular smooth muscle cell growth and differentiation, the
      present studies were conducted to evaluate the effect of diabetes mellitus on the
      proliferative behaviour of cultured aortic smooth muscle cells. METHODS: Male New
      Zealand White rabbits were made diabetic with a single intravenous injection of
      alloxan monohydrate (100 mg.kg-1) in saline. Primary cultures of smooth muscle
      cells were established from thoracic aortic segments of control and diabetic
      rabbits and used to develop multiple cell strains. The proliferative capability
      of secondary cultures was determined by measurements of [3H]-thymidine
      incorporation into DNA, cell counts, and protein content in control and diabetic
      cultures. The serum dependence of cellular growth was evaluated by incubation of
      cultured cells in growth medium supplemented with various fetal calf serum
      concentrations. RESULTS: Cultures of diabetic origin incorporated thymidine to a
      greater extent than control cultures. Although the efficiency of cell attachment
      was not different between control and diabetic cells, diabetic cells had a
      shorter population doubling time than control cells [41.08(SEM 4.15) h v
      58.08(6.79) h] and achieved higher final densities than control cultures. The
      serum dependence of smooth muscle cell cultures for viability and growth was
      different between the two groups. CONCLUSIONS: These findings support the
      hypothesis that diabetes induces changes in vascular smooth muscle cell
      proliferation which may be associated with the onset or progression of the
      atherogenic process observed in diabetes.

PMID- 8252582
TI  - Erythropoietin increases cytosolic free calcium concentration in vascular smooth
      muscle cells.
AB  - OBJECTIVES: The underlying pathophysiological mechanism leading to raised blood
      pressure after treatment with erythropoietin is a point of much discussion.
      Direct vasopressor effects of erythropoietin have been shown recently. The aim
      was to determine whether erythropoietin effects cytosolic free calcium
      concentration ([Ca2+]i in vascular smooth muscle cells. METHODS: The effect of
      erythropoietin on ([Ca2+]i was measured with the fluorescent dye fura2 in
      cultured vascular smooth muscle cells from Wistar Kyoto rats. RESULTS: Mean
      resting [Ca2+]i was 90.8(SEM 5.6) nM (n = 32). Addition of erythropoietin at
      concentrations of 100 U.ml-1 and 250 U.ml-1 increased [Ca2+]i to 112.3(5.0) nM (n
      = 23, p < 0.05) and 128.4(4.0) nM (n = 10, p < 0.01), respectively. Preincubation
      with erythropoietin caused a dose dependent increase in angiotensin II induced
      changes of [Ca2+]i in vascular smooth muscle cells. CONCLUSIONS: One mechanism of
      erythropoietin induced hypertension may be an increase in [Ca2+]i in vascular
      smooth muscle cells.

PMID- 8252583
TI  - Subcellular distribution of endogenous long chain acylcarnitines during hypoxia
      in adult canine myocytes.
AB  - OBJECTIVE: Previous studies from our laboratory showed a pronounced increase in
      the sarcolemmal accumulation of long chain acylcarnitines in isolated neonatal
      rat myocytes after a prolonged (60 minute) hypoxic interval. Because much shorter
      intervals of hypoxia are associated with electrophysiological alterations in
      adult cells, the present study was performed to assess the extent of sarcolemmal
      accumulation of long chain acylcarnitines during hypoxia in adult canine
      myocytes. METHODS: Cells were incubated (for 24 hours) with 3H-carnitine and the
      uniformity of incorporation into carnitine fractions was verified biochemically.
      Cells were exposed to hypoxia (PO2 < 15 mm Hg) for 10 or 20 minutes in the
      presence or absence of sodium 2-[5-(4-chlorphenyl)-pentyl]-oxirane-2-carboxylate
      (POCA; 10 microM), an inhibitor of carnitine acyltransferase I. Cells were
      processed for electron microscopical autoradiography with a technique to
      spatially fix endogenous long chain acylcarnitines with selective and complete
      removal of short chain and free carnitine. Grain distributions were analysed by
      the maximum likelihood method from digitised micrographs. RESULTS: Total mass of
      long chain acylcarnitines increased ninefold [42.3(3.3) to 374(42) pmol.mg-1
      protein] by 10 minutes of hypoxia and 15-fold [to 632(36) nmol.mg-1 protein] by
      20 minutes of hypoxia. Normoxic cells exhibited little long chain acylcarnitines
      in the sarcolemma, and modest amounts in mitochondria and cytoplasm. In hypoxic
      cells, content of long chain acylcarnitines in mitochondria and cytoplasm
      increased by a maximum of twofold. By contrast, long chain acylcarnitines
      increased 100-fold in the sarcolemma to 4.18 x 10(6) molecules.microns-3 after 10
      minutes of hypoxia. The increase in long chain acylcarnitines with hypoxia was
      completely prevented by pretreatment with POCA. CONCLUSION: Hypoxia in adult
      ventricular myocytes induces a rapid and preferential increase in endogenous long
      chain acylcarnitines within the sarcolemma.

PMID- 8252584
TI  - Systolic mechanical performance of heterotopically transplanted hearts in rats
      treated with cyclosporin.
AB  - OBJECTIVES: The aim was to compare left ventricular mechanical performance of the
      heterotopic cardiac transplant undergoing atrophy and the in situ recipient
      hearts of immunosuppressed rats. METHODS: The hearts of outbred male Wistar rats
      were transplanted, with a part of the lungs, into the abdomen of recipients of
      the same strain by attaching the stump of the aorta end to side to the abdominal
      aorta of the recipient. The animals were treated with cyclosporin A at a daily
      dose of 15 mg.kg-1 for seven consecutive days after the operation. Ventricular
      function was assessed in the isolated perfused "non-working" heart under
      isovolumetric conditions. RESULTS: Within three, 14, and 28 days after
      transplantation the mass of the left ventricle of the transplant decreased to 84,
      54, and 43% compared with corresponding recipients. The developed pressure,
      maximum rate of pressure development, and the slope of the systolic stress-strain
      relation were unaffected in the atrophic ventricles of the transplants; the rate
      of relaxation, however, significantly decreased. Similar results were obtained
      with inbred Lewis rats receiving no immunosuppression. CONCLUSIONS: The data
      indicate that systolic mechanical performance of the heterotopically transplanted
      hearts was maintained during the development of atrophy; the cardiotoxic effect
      of cyclosporin did not manifest itself under these conditions.

PMID- 8252586
TI  - A proischaemic action of nisoldipine: relationship to a decrease in perfusion
      pressure and comparison to dipyridamole.
AB  - OBJECTIVE: The calcium antagonist nisoldipine has recently been reported to
      induce rather than to attenuate ischaemia in some patients with stable angina.
      The aim of the study was to investigate the mechanisms underlying this
      proischaemic effect. METHODS: In 20 anaesthetised dogs systemic haemodynamic
      variables, regional myocardial blood flow (coloured microspheres), and systolic
      wall thickening (sonomicrometry) were measured during control conditions and
      following severe stenosis on the left circumflex coronary artery, before and
      after intravenous administration of equihypotensive doses of either nisoldipine
      (group I, n = 10) or dipyridamole (group II, n = 10). Finally, measurements were
      performed while the drug induced decreases in mean aortic pressure--18 (SD 6)
      mmHg in group I and 14(6) mm Hg in group II--were reversed by inflation of an
      intra-aortic balloon. RESULTS: The stenosis decreased posterior wall thickening
      to 50% of control, and posterior subendocardial blood flow from 1.48(0.27) to
      0.61(0.19) ml.min-1.g-1 in group I and from 1.49(0.23) to 0.62(0.18) ml.min-1.g-1
      in group II. Subendocardial blood flow was further decreased after administration
      of either nisoldipine [0.37(0.20) ml.min-1.g-1, p < 0.05 v stenosis] or
      dipyridamole [0.22(0.11) ml.min-1.g-1, p < 0.05 v stenosis]. Regional myocardial
      blood flow in the anterior region was increased. The drug induced reduction of
      subendocardial blood flow decreased posterior wall thickening further from
      9.3(2.1) to 6.2(3.9)% (p < 0.05 v stenosis, group I) and from 9.1(1.7) to
      4.3(2.4)% (p < 0.05 v stenosis, group II). When the drug induced decrease in
      aortic pressure was reversed, subendocardial blood flow again increased in group
      I [0.63(0.19) ml.min-1.g-1, p < 0.05 v stenosis and nisoldipine] whereas in group
      II it remained decreased [0.40(0.29) ml.min-1.g-1, NS v stenosis and
      dipyridamole]. There was restoration of posterior wall thickening in group I
      [10.4(3.8)%, p < 0.05 v stenosis and nisoldipine], but not in group II
      [5.2(3.5)%, NS v stenosis and dipyridamole]. CONCLUSIONS: Nisoldipine and
      dipyridamole decrease subendocardial blood flow and contractile function distal
      to a severe stenosis when aortic pressure is decreased. No aggravation of
      ischaemia by nisoldipine is seen when hypotension is prevented. In contrast,
      dipyridamole in the absence of hypotension still induces a redistribution of flow
      at the expense of the ischaemic region.

PMID- 8252585
TI  - Cardiac cell toxicity induced by 4-hydroperoxycyclophosphamide is modulated by
      glutathione.
AB  - OBJECTIVE: Cardiac myocytes were exposed to 4-hydroperoxycyclophosphamide (4-HC,
      an activated derivative of cyclophosphamide) to assess whether early ionic events
      are associated with the dose limiting toxicity of this chemotherapeutic agent.
      METHODS: Primary cultures of embryonic chick cardiac myocytes were grown to
      confluency and then exposed to a medium containing 4-HC. Cellular sodium,
      potassium, and calcium contents were measured by atomic absorption
      spectrophotometry and related to protein and ATP content. Pretreatment of the
      cultured heart cells with glutathione depleting or enhancing agents provided the
      basis for evaluating the involvement of glutathione in the 4-HC-induced
      cytotoxicity. RESULTS: Administration of 150 microM 4-HC to cardiac myocytes
      resulted in increases in cellular sodium and calcium contents and decreases in
      potassium, ATP, and protein contents. Pretreatment of cardiac myocytes with L
      buthionine-SR-sulphoximine, a specific inhibitor of gamma-glutamylcysteine
      synthetase, depleted cellular glutathione to 12% of control and significantly
      reduced the minimum concentration of 4-HC causing cytotoxic changes. Conversely,
      elevation of cellular thiol content by the pretreatment of cardiac myocytes with
      glutathione monoethyl ester (but not glutathione) provided protection against 4
      HC induced cytotoxicity. CONCLUSIONS: Cellular glutahione concentration can
      markedly influence the 4-HC induced changes in cellular ion content and ATP,
      which are early indicators of 4-HC induced cytotoxicity.

PMID- 8252587
TI  - Effect of hypoxia and reoxygenation on the isolated rabbit heart determined by
      monoclonal antimyosin antibody uptake.
AB  - OBJECTIVE: The aim was to examine the effect of hypoxia and reoxygenation upon
      the isolated rabbit heart, and to determine whether or not irreversible tissue
      injury develops in association with the reintroduction of molecular oxygen to the
      previously hypoxic heart. METHODS: Isolated rabbit hearts suspended on a
      Langendorff apparatus and perfused with a modified Krebs-Henseleit buffer were
      subjected to either 5 or 30 min hypoxia and, when applicable, followed by 45 min
      reoxygenation. The effect of hypoxia and reoxygenation upon the isolated heart
      was determined with a 125labelled monoclonal antibody to the intracellular
      protein myosin. Determination of tissue creatine kinase release and morphological
      analysis, using lanthanum chloride as a marker of vessel damage, were also
      performed to document the uptake of antimyosin with myocardial tissue injury.
      RESULTS: Hearts subjected to 30 min hypoxia followed by 45 min reoxygenation
      showed a significant increase in antimyosin uptake when compared to hearts
      exposed to 30 min hypoxia. Creatine kinase release and morphological analysis
      showed an increase in intracellular damage in hearts receiving 30 min hypoxia and
      45 min reoxygenation when compared to hearts receiving 30 min hypoxia without
      subsequent reoxygenation. Hearts subjected to 5 min hypoxia followed by
      reoxygenation did not show a significant increase in antimyosin uptake as
      compared to continuously oxygenated control hearts or hearts made hypoxic for 5
      min without subsequent reoxygenation. CONCLUSIONS: Antimyosin antibody binding
      increased in hearts subjected to hypoxia and reoxygenation compared to hearts
      subjected to hypoxia without reoxygenation. The data provide compelling evidence
      that reoxygenation of hypoxic tissue exacerbates the extension of cellular
      damage. The ability of superoxide dismutase and catalase to decrease antimyosin
      uptake suggests that reactive oxygen species play a role in reoxygenation induced
      myocardial damage. This study also provides evidence that the labelled antimyosin
      antibody provides a convenient approach to quantitate the extent of damage
      induced by hypoxia with and without subsequent reoxygenation.

PMID- 8252588
TI  - Investigation of the mechanisms underlying the increased contraction of
      hypertrophied ventricular myocytes isolated from the spontaneously hypertensive
      rat.
AB  - OBJECTIVE: The aim was to investigate the cellular mechanisms responsible for the
      increased contraction of left ventricular myocytes isolated from the
      spontaneously hypertensive rat (SHR). METHODS: Single myocytes were isolated
      enzymatically from the left ventricles of SHR, Wistar-Kyoto (WKY), and Wistar
      rats. WKY and Wistar myocytes were used as normotensive controls. Cytoplasmic
      calcium was measured with Fura-2 and contraction was measured optically. Membrane
      potential was measured with microelectrodes and cells were voltage clamped to
      measure the amplitude of L-type calcium current (iCa). RESULTS: Under action
      potential conditions, SHR myocytes had a larger calcium transient and an
      increased sarcoplasmic reticular calcium content compared to normotensive
      myocytes. There was no detectable difference in the resting cytoplasmic calcium
      concentration between SHR and control myocytes. SHR myocytes also had a prolonged
      action potential compared to normotensive cells. However, when cells were voltage
      clamped and short pulses of 120 ms duration were applied (a similar duration of
      depolarisation to the action potential), the difference in the calcium transient
      or contraction between SHR and normotensive myocytes was abolished. SHR myocytes
      had an unchanged amplitude of ICa in comparison to control myocytes, and there
      was no detectable difference in the myofilament response to calcium between SHR
      and control myocytes. CONCLUSIONS: (1) Hypertrophied SHR myocytes stimulated with
      action potentials had an increased calcium transient compared to normotensive
      cells. The greater calcium transient in the SHR cells is likely to be a major
      factor responsible for their increased contraction. (2) SHR myocytes had a
      prolonged action potential in comparison to normotensive cells. (3) The amplitude
      of ICa and myofilament response to calcium were unchanged in SHR myocytes,
      suggesting that these factors do not play a role in the increased contraction of
      these cells. (4) Since the difference between SHR and control cells was abolished
      by voltage clamping the cells to prevent the difference of action potential, it
      is unlikely that an alteration of intrinsic mechanisms in SHR myocytes is
      responsible for their increased contraction. Rather, it suggests that the
      prolonged action potential of SHR myocytes plays a important role in causing
      their increased calcium transient and contraction. Our results indicate that the
      prolonged action potential in SHR cells results in an increased calcium content
      of the sarcoplasmic reticulum, which leads to a greater sarcoplasmic reticular
      calcium release upon stimulation and an increased contraction.

PMID- 8252589
TI  - Membrane current changes in left ventricular myocytes isolated from guinea pigs
      after abdominal aortic coarctation.
AB  - OBJECTIVE: The aim was to look for membrane current changes as a basis for the
      prolongation of action potential duration in left ventricular myocytes following
      abdominal aortic coarctation. METHODS: Immature female guinea pigs underwent
      laparotomy and an aortic coarctation was fashioned immediately distal to the
      renal arteries. After 20 weeks the hearts were removed and single myocytes were
      isolated from the left ventricles by standard enzymatic techniques. The switch
      clamp technique was used. RESULTS: Heart weight:body weight ratio was increased
      by 7% in the coarctation group (p < 0.01). Systolic left ventricular pressure was
      59(SEM 4) mm Hg in control and 76(7) mm Hg in coarctation animals (p < 0.05).
      Cell capacity was increased by 21% in the coarctation group (p < 0.05), and mean
      resting potential was 4.6 mV more negative in this group (p < 0.001). Action
      potential duration at 90% repolarisation was 310(17) ms in the control group (n =
      22) and 358(13) ms in the coarctation group (n = 34, p < 0.05). Peak density of L
      type calcium current was -8.6(0.4) pA.pF-1 in control and -11.1(0.7) pA.pF-1 in
      coarctation cells (p < 0.01). The regression line for calcium current versus cell
      capacity was shifted to higher calcium currents in the coarctation group. The
      half inactivation potential for this current was shifted by 11.5 mV (p < 0.01).
      Calcium-activated tail currents were larger and the envelope of tail currents was
      prolonged in the coarctation cells. No significant differences were found in the
      amplitude of IK or of IKl. CONCLUSIONS: After infrarenal aortic coarctation,
      action potential duration of left ventricular myocytes is prolonged. This
      prolongation may be attributed to an increase in calcium current density and a
      shift of its inactivation variable, together with an increased magnitude and
      prolonged time course of sodium-calcium exchange current. These current changes
      are potentially arrhythmogenic.

PMID- 8252590
TI  - Leucocyte depletion attenuates the early increase in myocardial capillary
      permeability to small hydrophilic solutes following ischaemia and reperfusion.
AB  - OBJECTIVE: The aim was to assess the significance of polymorphonuclear leucocytes
      on the myocardial capillary permeability to a small hydrophilic indicator, on the
      vascular tone of the resistance vessels, and on contractile function following
      ischaemia and reperfusion. METHODS: Open chest, anaesthetised dogs were
      randomised to treatment with polyclonal antibody against polymorphonuclear
      leucocytes (anti-PMN group) or non-specific antibody (control group), and
      subjected to 40 min of coronary occlusion followed by 3 h of reperfusion. The
      capillary extraction fraction and the myocardial plasma flow rate were
      quantitated in vivo by intracoronary indicator bolus injection and external
      registration of the washout, and the capillary permeability-surface area product
      was calculated. Postischaemic vasodilator tone in the myocardial resistance
      vessels was measured by the local 133xenon washout method. RESULTS: 20 dogs were
      included (10 in each group), and 13 dogs completed the ischaemia-reperfusion
      protocol (anti-PMN group, n = 7; control group, n = 6). In the anti-PMN group,
      blood polymorphonuclear leucocyte counts were reduced to a minimum of 15% of
      pretreatment values. After ischaemia and 5 min reperfusion, the capillary
      extraction increased by 17% in the control group but decreased by 22% in the anti
      PMN group (p < 0.05). The corresponding capillary permeability-surface area
      product increased by 22% in the control group, but decreased by 16% in the anti
      PMN group (p < 0.05). Neither maximum myocardial plasma flow during reactive
      hyperaemia nor contractile function were influenced by anti-PMN treatment.
      CONCLUSIONS: Polymorphonuclear leucocytes appear to participate in the increase
      in myocardial capillary permeability observed early after reperfusion following a
      40 min period of ischaemia, but do not influence postischaemic vascular tone or
      postischaemic contractile function. During normal physiological conditions
      reduction of the circulating polymorphonuclear leucocyte counts did not induce
      significant changes in myocardial capillary permeability.

PMID- 8252591
TI  - Ventricular adenine nucleotide translocator mRNA is upregulated in dilated
      cardiomyopathy.
AB  - OBJECTIVE: A disturbed energy transfer involving the adenine nucleotide
      translocator across the inner mitochondrial membrane has been suggested to be one
      specific pathogenetic mechanism in dilated cardiomyopathy. Pretranslational
      steady state expression of this protein in dilated cardiomyopathy was
      investigated. METHODS: Concentrations of adenine nucleotide translocator were
      quantified by solution hybridisation. The enzyme or protein expressions of
      citrate synthase, lactate dehydrogenase, and creatine kinase with isozymes were
      determined. Analysis was performed on specimens from the left and right
      ventricles from six organ donor hearts, six explanted hearts with dilated
      cardiomyopathy, two explanted hearts with ischaemic cardiomyopathy, and from
      papillary muscles from seven patients operated on for mitral regurgitation.
      RESULTS: The ejection fraction in patients with mitral regurgitation was 50(10)%,
      significantly higher (p < 0.001) than in patients with dilated cardiomyopathy
      (23(5))%. In mitral regurgitation and in ischaemic cardiomyopathy left
      ventricular adenine nucleotide translocator mRNA concentrations did not differ
      from those in donor hearts. In dilated cardiomyopathy, adenine nucleotide
      translocator mRNA concentrations were significantly increased (p < 0.001).
      Upregulation was more pronounced in right ventricular than in left ventricular
      myocardium (p < 0.01). The lactate dehydrogenase M subunit fraction was increased
      to a similar degree in dilated cardiomyopathy and in mitral regurgitation (p <
      0.05). Citrate synthase activity was significantly decreased only in dilated
      cardiomyopathy (p < 0.005). On the other hand, the creatine kinase B subunit
      content was significantly higher in mitral regurgitation than in dilated
      cardiomyopathy (p < 0.001). CONCLUSIONS: Despite signs of increased anaerobic and
      depressed oxidative capacities, dilated cardiomyopathy was specifically
      characterised by pretranslational upregulation of adenine nucleotide
      translocator.

PMID- 8252592
TI  - Increased expression of the lactate dehydrogenase M subunit in myocardial regions
      with decreased thallium uptake.
AB  - OBJECTIVE: In ischaemic heart disease, the heart muscle is subjected to repeated
      episodes of regional ischaemia or to a constant underperfusion. The purpose of
      the present investigation was to study the myocardial metabolic adaptation to
      this stress. METHODS: Eighteen male patients with ischaemic heart disease were
      studied by biopsies taken from the left ventricular septum during bypass surgery.
      Citrate synthase, total lactate dehydrogenase and its H and M subunits, coenzyme
      Q10, and myoglobin were determined in all biopsies. Concentrations of ATP, ADP,
      and AMP were determined and energy charge calculated in the biopsies from the
      patients with ischaemic heart disease. Biopsies from the septal region of hearts
      obtained from brain dead kidney and liver donors were used as reference and
      preoperative myocardial thallium scintigraphy was performed in the patients with
      ischaemic heart disease to relate the myocardial biochemical markers to thallium
      uptake at the biopsy site. RESULTS: Myocardial activities of citrate synthase as
      well as contents of coenzyme Q10 and myoglobin in patients with ischaemic heart
      disease were not different from those of the reference group, and no linear
      relation was found between these three markers on the one hand and thallium
      uptake on the other. The energy charge was directly related and the M subunit of
      lactate dehydrogenase inversely related to the thallium uptake. CONCLUSION: The
      results suggest an absence of adaptation to ischaemia in terms of increased
      myocardial oxidative capacity and O2 transport and storage capacity. Furthermore,
      it is indicated that a stressed energy metabolism with increasing severity of
      ischaemic heart disease enhances anaerobic metabolism and induces a shift in
      myocardial lactate dehydrogenase subunit fractions.

PMID- 8252593
TI  - Post-ejection wall thickening as a marker of successful short term hibernation.
AB  - OBJECTIVE: Short term hibernating myocardium is characterised by a decrease in
      contractile function in proportion to the reduced blood flow, the recovery of
      creatine phosphate despite ongoing ischaemia, a recruitable inotropic reserve,
      and the absence of necrosis. During acute myocardial ischaemia systolic wall
      thickening decreases and post-ejection wall thickening develops. The extent of
      post-ejection thickening during severe ischaemia correlates with the recovery of
      contractile function during reperfusion. Whether the extent of post-ejection wall
      thickening can also distinguish short term hibernating myocardium from more
      severely ischaemic, infarcting myocardium and thus predict the amount of viable
      tissue was tested in 13 anaesthetised pigs. METHODS: The left anterior descending
      coronary artery (LAD) was cannulated and perfused at constant flow. After control
      measurements of regional myocardial blood flow (with radiolabelled microspheres)
      and wall thickening (sonomicrometry), coronary inflow was reduced to produce a
      reduction in regional contractile function by 60-100%. After 85 minutes of
      ischaemia, dobutamine was infused into the LAD for five minutes to determine the
      extent of inotropic reserve. Transmural biopsies were taken to measure regional
      myocardial creatine phosphate content and infarct size was determined after two
      hours of reperfusion by staining with triphenyl tetrazolium chloride. RESULTS:
      The extent of post-ejection wall thickening after 85-90 minutes of ischaemia
      correlated with the myocardial creatine phosphate content (r = 0.812, n = 11, p <
      0.01) and the extent of the dobutamine recruitable inotropic reserve (r = 0.783,
      n = 7, p < 0.05). A negative correlation existed between the extent of post
      ejection wall thickening and % infarct size (r = -0.699, n = 10, p < 0.05 for the
      transmural piece of tissue containing the ultrasonic crystals; r = -0.743, n =
      10, p < 0.05 for the area of the left ventricle at risk). Finally, post-ejection
      wall thickening after 85-90 minutes of ischaemia correlated with the recovery of
      contractile function at 30 minutes reperfusion (r = 0.657, n = 10, p < 0.05).
      CONCLUSION: The extent of post-ejection wall thickening may indicate the amount
      of viable tissue after 85-90 minutes of low flow ischaemia. The greater the post
      ejection wall thickening, the more myocardium is successfully hibernating.

PMID- 8252594
TI  - Alterations in circulating and cardiac tissue concentrations of brain natriuretic
      peptide in spontaneously hypertensive rats.
AB  - OBJECTIVE: This study was designed to investigate the modification of plasma and
      cardiac tissue brain natriuretic peptide concentrations in spontaneously
      hypertensive rats and Wistar-Kyoto rats in relation to those of atrial
      natriuretic peptide during the development of hypertension. METHODS: Blood
      pressure, tissue weight, and plasma and cardiac tissue atrial natriuretic peptide
      and brain natriuretic peptide concentrations were measured in conscious 5, 10,
      and 18 week old, spontaneously hypertensive, and in corresponding normotensive
      rats. Pharmacokinetics of atrial natriuretic peptide and brain natriuretic
      peptide were also examined. RESULTS: Plasma concentrations of both atrial
      natriuretic peptide and brain natriuretic peptide in hypertensive rats increased
      significantly with development of hypertension. The pattern was not in parallel,
      so that the brain natriuretic peptide/atrial natriuretic peptide ratio was high
      in spontaneously hypertensive rats. Concentrations of brain natriuretic peptide
      in the cardiac ventricle were already higher in hypertensive rats than in
      controls as early as 5 weeks of age, whereas atrial natriuretic peptide
      concentrations in the ventricle, predominantly in the left ventricles, and the
      highest brain natriuretic peptide/atrial natriuretic peptide ratio was in the
      left ventricles from 18 week old spontaneously hypertensive rats.
      Pharmacokinetics showed that the plasma half lives of atrial natriuretic peptide
      and brain natriuretic peptide were not different between the two strains.
      CONCLUSIONS: Although raised blood pressure stimulates both atrial natriuretic
      peptide and brain natriuretic peptide, production of brain natriuretic peptide in
      the ventricles is already increased in the prehypertensive stage, and in older
      hypertensive rats, it is more responsive to progression of hypertension than
      atrial natriuretic peptide. It is suggested that regulation of production and
      secretion of the two natriuretic peptides is not temporally coordinated during
      development of hypertension in this model.

PMID- 8252595
TI  - Effects of genetic hypertension and nutritional anaemia on ventricular
      remodelling and myocardial damage in rats.
AB  - OBJECTIVE: In order to determine whether alterations in cardiac function and
      structure occur early in life in spontaneously hypertensive rats (SHR) and
      whether the addition of a volume load would affect myocardial growth and
      haemodynamic performance, SHR were exposed to an iron and copper deficient diet
      for 12 weeks (SHR-A) and compared with untreated SHR and Wistar Kyoto controls
      (WKY). RESULTS: Systolic arterial blood pressure increased in SHR, whereas
      nutritional anaemia prevented the rise of blood pressure in SHR-A. The diet
      employed provoked a severe hypochromic microcytic anaemia with a marked reduction
      in blood viscosity and increased volume load on the heart in SHR-A. Genetically
      determined hypertension alone induced a 16% increase in left ventricular weight
      and an increase in left ventricular peak systolic pressure (LVPSP) and +dP/dt.
      The superimposition of anaemia resulted in a 43% expansion in left ventricular
      weight with a decrease in LVPSP and +dP/dt, and an increase in left ventricular
      end diastolic pressure. Wall thickening and a preservation of chamber volume
      occurred in SHR, while SHR-A had a degree of ventricular dilatation which
      exceeded the extent of wall thickening. However, genetic hypertension was
      accompanied by myocardial tissue injury which was fully prevented by the addition
      of nutritional anaemia. Moreover, the capillary volume was decreased in SHR and
      increased in SHR-A. CONCLUSIONS: Genetically determined hypertension in
      combination with anaemia results in eccentric ventricular hypertrophy and cardiac
      dysfunction in spite of an increase in capillary luminal volume and limited
      structural damage.

PMID- 8252596
TI  - Electrophysiological effects of a new class III antiarrhythmic agent (E-4031) on
      the conduction and refractoriness of the in vivo human atrium.
AB  - OBJECTIVE: The aim was to test the efficacy of a new class III drug, E-4031, on
      human atrial muscle in vivo. METHODS: Electrophysiological measurements were
      performed in 10 patients, age 54(SD 11) years, before and during the continuous
      infusion of E-4031 (0.15 microgram.kg-1.min-1) which followed an initial dose of
      9 micrograms.kg-1 x 5 min-1. Extrastimuli at 500 ms were delivered from the right
      atrial appendage, high lateral right atrium, and low lateral right atrium. The
      effective refractory period, repetitive atrial firing zone, and fragmented atrial
      activity zone were assessed at three sites in the right atrium. The conduction
      delay zone from the stimulus artefact to the distal electrode pair at the
      coronary sinus was also measured. RESULTS: E-4031 caused a significant increase
      in overall right atrial effective refractory period from 210(SD 29) to 232(26) ms
      (p < 0.001, n = 30 sites). There were significant decreases in the incidence of
      repetitive atrial firing (67% to 37%: p < 0.005), in the repetitive atrial firing
      zone [23(20) to 11(22) ms: p < 0.01], and in the fragmented atrial activity zone
      [15(22) to 3(8) ms: p < 0.005], but no significant change in the conduction delay
      zone. However, E-4031 significantly prolonged the longest coupling interval that
      elicited conduction delay, from 249(31) ms to 267(28) ms (p < 0.01). E-4031 had
      no effect on the conduction time except at coupling intervals close to the atrial
      effective refractory period. CONCLUSION: These results suggest that E-4031 has a
      potential effect in the treatment of human paroxysmal atrial fibrillation.

PMID- 8252597
TI  - Lack of myocardial lipid peroxidation during acute reperfusion injury in perfused
      guinea pig hearts.
AB  - OBJECTIVE: The aim was to test the hypothesis that free radical induced lipid
      peroxidation contributes to the arrhythmias and contractile changes associated
      with reperfusion. Evidence of oxidative stress in the membrane lipids was sought
      using four different approaches: (1) determination of lipid peroxidation
      metabolites; (2) direct detection of free radical formation using a lipophilic
      spin trap; (3) assessment of lipid peroxidation substrate; and (4) evaluation of
      antioxidant levels in the heart. METHODS: Electrical and contractile functions
      were monitored in isolated perfused guinea pig hearts subjected to ischaemia for
      20 or 60 min followed by reperfusion for 1 or 20 min. The reperfused hearts were
      flushed with cold phosphate buffer with EDTA and the ventricles weighed and
      homogenised. Malonaldehyde content was determined using both a thiobarbituric
      acid spectrophotometric assay and a p-aminobenzoate spectrofluorescence assay. A
      lipophilic spin trap, PBN, was injected into guinea pigs 2 h before they were
      killed. Hearts containing spin traps were perfused for 5 min, then subjected to
      ischaemia followed by 1 min reperfusion. Lipid extracts containing PBN were
      examined using electron paramagnetic resonance spectroscopy. The content of
      polyunsaturated fatty acids and alpha tocopherol were determined by GLC and HPLC,
      respectively. RESULTS: Malonaldehyde content of the heart tissues did not
      increase during any combination of ischaemic and reperfusion episodes. The assays
      were effective at detecting raised malonaldehyde in hearts perfused with either
      0.5 mM malonaldehyde standard or 0.5 mM cumene hydroperoxide. No spin adducts
      were found in either the extracted membrane lipids or the aqueous layer. Spin
      adducts were detected in myocardial lipids from animals exposed to non-lethal
      doses of gamma irradiation, confirming the presence of the spin trap in the heart
      tissue and the ability to detect spin adducts when formed. There were no
      differences in the percentage of total fatty acids that were polyunsaturated
      between reperfused hearts and continously perfused controls. Furthermore, alpha
      tocopherol content of the hearts exposed to ischaemia and reperfusion was not
      decreased relative to hearts perfused without an ischaemic episode. CONCLUSIONS:
      The results suggest that the early functional disturbances during reperfusion are
      not related to peroxidation of membrane lipids.

PMID- 8252598
TI  - Exercise capacity of rats remains unaffected by a chronic pressure overload.
AB  - OBJECTIVE: The aim was to determine if the adaptive responses of the myocardium
      to a chronic pressure overload affected cardiovascular performance when evaluated
      under conditions of increased functional demand. METHODS: Selected female rats
      were made hypertensive by abdominal aortic constriction. After eight weeks of
      aortic constriction, cardiovascular responses and work performance were measured
      during a maximal treadmill exercise bout. RESULTS: Aortic constriction increased
      mean arterial pressure and the relative quantity of the slow ATPase myosin
      isoform, V3, relative to untreated controls (p < 0.05). Both groups had similar
      oxygen consumptions (VO2), heart rates (HR), and oxygen pulses (VO2/HR) at rest
      and throughout the exercise test. Both groups reached their VO2 max at the same
      exercise duration and exercise intensity (40.4 m.min-1). Soleus citrate synthase
      activity was not different between the groups. CONCLUSIONS: These similarities in
      work capacity, VO2, oxygen pulse, and muscle oxidative capacity suggest (1) that
      cardiovascular and exercise capacity can both be maintained in spite of the
      presence of a chronic pressure overload; (2) that after two months of aortic
      constriction the heart appears to be in a compensated stage of adaptation; and
      (3) that the cardiac myosin isoenzyme profile may have little direct effect on
      cardiovascular functional capacity.

PMID- 8252599
TI  - Cardiac structural remodelling after treatment of spontaneously hypertensive rats
      with nifedipine or nisoldipine.
AB  - OBJECTIVE: The aim was to determine if long term treatment with nifedipine or
      nisoldipine affects structural remodelling of cardiac myocytes and is effective
      in attenuating or preventing reparative and reactive myocardial fibrosis in
      essential hypertension. METHODS: Five and a half month old male spontaneously
      hypertensive rats and Wistar Kyoto (WKY) rats received either 1000 ppm nifedipine
      or nisoldipine or no treatment (controls) for 22 weeks. Haemodynamic variables
      were measured and hearts recovered from animals of each group. Cardiac myocytes
      were isolated by retrograde coronary perfusion with collagenase. Cell volume was
      determined by Coulter analysis, cell length by direct measurement, and cross
      sectional area by volume/length. Cardiac myocyte number was calculated for both
      ventricles. Tissue sections from perfusion fixed hearts were stained with
      picrosirius red and myocardial collagen was analysed. Reparative fibrosis was
      assessed by the presence of microscopic scarring and reactive (interstitial and
      perivascular) fibrosis was quantified. RESULTS: Nifedipine and nisoldipine
      significantly decreased systolic and diastolic blood pressure in spontaneously
      hypertensive rats, although normotensive pressures did not result. Left
      ventricular weight relative to body weight was significantly decreased in
      nifedipine and nisoldipine treated compared with untreated spontaneously
      hypertensive rats, although values remained significantly greater than WKY
      controls. Cardiac myocyte volume was slightly decreased with attenuation of blood
      pressure in spontaneously hypertensive rats, but no significant differences were
      found. Cardiac myocyte number for each ventricle was similar between groups.
      Microscopic scarring was significantly decreased in nifedipine and nisoldipine
      treated compared with untreated spontaneously hypertensive rats and interstitial
      and perivascular fibrosis were substantially reduced. CONCLUSIONS: Nifedipine and
      nisoldipine: (a) attenuate hypertension and decrease left ventricular mass in
      spontaneously hypertensive rats, but the associated decrease in myocyte size was
      not significant; (b) are cardioprotective as indicated by a significant decrease
      in the incidence of microscopic scarring; and (c) decrease the extent of
      reactive, both interstitial and perivascular, fibrosis normally found in
      untreated spontaneously hypertensive rats. Nifedipine and nisoldipine have the
      potential to positively alter myocardial pathology in essential hypertension.

PMID- 8252600
TI  - Identification and immunolocalisation of annexins V and VI, the major cardiac
      annexins, in rat heart.
AB  - OBJECTIVE: The heart contains proteins of the annexin family, a unique group of
      calcium binding proteins. This study was aimed at identifying the major cardiac
      annexins and determining their distribution in the rat heart. METHODS: Annexins
      were isolated by affinity chromatography and purified by ion exchange high
      pressure liquid chromatography. Identification of isolated proteins by
      immunoblotting was confirmed by partial amino acid sequence determination.
      Antisera raised against the isolated proteins were used for immunohistochemistry
      by the avidin-biotin-peroxidase technique. RESULTS: Two annexins were isolated
      and purified. Amino acid sequencing confirmed their identities as annexin V and
      VI. Immunohistochemistry showed that both annexins were present in cardiac
      myocytes and non-myocytes, but a distinct pattern of distribution was seen for
      each annexin. Annexin V immunoreactivity was enhanced in the atria compared with
      the ventricles, whereas annexin VI was more uniformly distributed. In individual
      cardiac myocytes annexin V was distributed throughout the cell by contrast with
      annexin VI, which localised to the sarcolemma. Intercalated discs displayed
      immunoreactivity for both annexins, most prominently for annexin VI. The most
      striking immunoreactivity for annexin V occurred in vascular endothelial cells,
      both in the microcirculation and in the major coronary vessels. Immunoreactivity
      for annexin VI in vascular structures was localised to the nuclei of endothelial
      and smooth muscle cells. CONCLUSIONS: Annexins V and VI are the major cardiac
      annexins. The localisation of these annexins to different components of cardiac
      myocytes will serve to direct the search for their functions in the heart. The
      striking immunoreactivity for annexins, particularly annexin V, in the coronary
      vessels indicates that the functions of cardiac annexins include a role in the
      coronary circulatory system.

PMID- 8252601
TI  - Improvement of doxorubicin induced cardiomyopathy in rats treated with insulin
      like growth factor I.
AB  - OBJECTIVES: This study was designed to assess the effects of treatment with
      insulin-like growth factor-I (IGF-I) on cardiac function and structure in rats
      with an established cardiomyopathy. METHODS: Adult male Wistar rats were injected
      with doxorubicin (2 mg.kg-1 subcutaneously) weekly for 12 weeks and either rhIGF
      I (0.8 mg.kg-1.day-1; n = 16, D-I group) or saline (n = 25, D-S group)
      subcutaneously via an osmotic pump from weeks 9 to 12. A non-doxorubicin injected
      control group was also studied. After 12 weeks survivors were anaesthetised and
      cardiac output determined with radiolabelled microspheres. At postmortem pleural
      effusion and ascitic volumes were measured and the heart was removed for
      histological examination by light and transmission electron microscopy. RESULTS:
      Doxorubicin treated animals showed less mean weight gain from week 2 than the
      untreated control group. Animals treated with IGF-I from week 9 showed a
      significant (p < 0.05) but non-sustained increase in weight. Survival to 12 weeks
      was 56% in the D-I group and 44% in the D-S group (p = 0.2). Evidence of cardiac
      failure was seen in the D-I and the D-S groups, but there was a tendency (p =
      0.06) for less ascites in the D-I group (21 (SEM 8) ml) than in the D-S group (46
      (10) ml). Cardiac output was significantly higher in the D-I than in the D-S
      group (132 (7.2) v 91.4 (6.4) ml.min-1, p < 0.01), as was stroke volume (0.323
      (0.03) v 0.226 (0.02) ml, p < 0.01). There was focal cardiac damage in both D-I
      and D-S animals. Scattered groups of myocytes showed prominent vacuolation of the
      nuclear envelope, sarcoplasmic reticulum, and t tubular system, mild to severe
      mitochondrial swelling, and loss of orientation and definition of myofibrils. No
      clear morphological differences were evident between the two groups. CONCLUSIONS:
      Administration of IGF-I may improve the function of damaged myocardium, although
      the mechanisms are unclear. Further studies with earlier coadministration of IGF
      I, quantitative histological analysis, and with other models of cardiac injury
      are indicated.

PMID- 8252602
TI  - Combined effect of the 5-HT2 receptor antagonist DV-7028 and aspirin or heparin
      on coronary cyclic flow reductions in dogs.
AB  - OBJECTIVE: The aim was to study the combined effect of DV-7028, a selective 5
      hydroxytryptamine2 receptor antagonist, and aspirin or heparin on cyclic flow
      reductions in the canine coronary artery. METHODS: Anaesthetised open chest
      beagle dogs under artificial respiration were used. Cyclic flow reductions were
      induced by partial occlusion of the left anterior descending coronary artery at
      the site of endothelial injury. After induction of cyclic flow reductions, test
      drugs were given to the animals intravenously. RESULTS: DV-7028 (0.1 mg.kg-1)
      reduced the frequency of cyclic flow reductions by 77% and improved the nadir of
      coronary blood flow velocity that indicated the severity of cyclic flow
      reductions. Also, aspirin (1 or 3 mg.kg-1) or heparin (200 U.kg-1) attenuated the
      cyclic flow reductions. In experiments with drug combinations, DV-7028 was given
      to animals that had already received aspirin (1 mg.kg-1) or heparin (200 U.kg-1).
      DV-7028 (0.1 mg.kg-1) completely abolished the cyclic flow reductions remaining
      after aspirin treatment in three of four animals. Heparin inhibited the cyclic
      flow reductions in one of five animals and the addition of DV-7028 abolished the
      remaining cyclic flow reductions in the other four animals. After combined
      injection of DV-7028 with aspirin or heparin, the coronary blood flow with
      cyclical reductions returned to the baseline. CONCLUSIONS: The 5-HT2 receptor
      antagonist DV-7028 can inhibit the cyclic flow reductions that are resistant to
      aspirin or heparin. The combined regimen of DV-7028 and aspirin or heparin in
      treatment of acute coronary stenosis is more effective than that of aspirin or
      heparin alone.

PMID- 8252603
TI  - Hypoxia and reoxygenation in the isolated rabbit heart.

PMID- 8252604
TI  - Effects of athletic training on neural control of heart rate.

PMID- 8252605
TI  - Ontogeny of corticosteroid receptors in the brain.
AB  - 1. In the brain, glucocorticoids bind to both the glucocorticoid receptor (GR)
      and the mineralocorticoid receptor (MR). These receptors show clearly distinct
      developmental patterns in the infant rat. 2. Low levels of GRs are present around
      the time of birth throughout the brain. Concentrations rise slowly, and do not
      achieve adult levels until the third week of life, approximately. GR affinity for
      corticosterone is higher perinatally than at later ages. Receptor
      microdistribution changes dramatically during ontogeny. In particular, certain
      regions, such as the suprachiasmatic nucleus of the hypothalamus, express high
      levels of receptor only during the first week of life. GRs may show impaired
      capacity to undergo transformation and/or nuclear translocation during the second
      postnatal week. Environmental manipulations during early ontogeny (e.g., early
      handling) may have permanent effects on GR capacity. 3. MRs are present at very
      low concentrations in the first days of life. Binding capacity rises rapidly
      thereafter and resembles that found in the adult by the end of 1 week. Neither
      binding affinity in vitro nor overall distribution changes with age. As in the
      adult, low doses of corticosterone, in vivo, bind mainly to the MRs. Levels of
      corticosterone are low and relatively unperturbable in the intact infant rat. It
      is likely, therefore, that most of the physiological actions of this hormone
      during this period are mediated by the MR.

PMID- 8252606
TI  - Molecular basis for the development of individual differences in the hypothalamic
      pituitary-adrenal stress response.
AB  - 1. Several years ago, investigators described the effects of infantile handling
      on the development of hypothalamic-pituitary-adrenal (HPA) responses to stress in
      the rat. Rat pups exposed to brief periods of innocuous handling early in life
      showed reduced HPA responses to a wide variety of stressors, and the effect
      persists throughout the life of the animal. These effects are robust and provide
      an excellent model for understanding how early environmental stimuli, which are
      external to the organism, alter neural differentiation and, thus, neuroendocrine
      responsivity to stress. 2. This paper reviews the endocrine mechanisms affected
      by early handling and our current understanding of the neural transduction of
      environmental events and their effects at the level of the target neurons (in the
      hippocampus and frontal cortex). 3. In brief, handling serves to increase
      glucocorticoid receptor gene transcription, increasing sensitivity to
      glucocorticoid negative feedback regulation and, thus, altering the activity
      within hypothalamic corticotropin-releasing factor/vasopressin neurons. Together
      these changes serve to determine neuroendocrine responsivity to stress.

PMID- 8252607
TI  - Regulation of adrenocorticosteroid receptor mRNA expression in the central
      nervous system.
AB  - 1. The adrenocorticosteroid receptors are hormone-activated transcription factors
      that have the potential to influence gene expression in a wide variety of CNS
      neurons. This review summarizes the present state of knowledge regarding the
      localization and regulation of glucocorticoid (or type II corticosteroid)
      receptor and mineralocorticoid (or type I corticosteroid) receptor mRNAs in
      brain, from the perspective of their potential influence on a wide variety of
      hormone-responsive genes. 2. Corticosteroid receptors are widely but not
      uniformly localized in the CNS and exhibit very complex regulation by
      glucocorticoids, gonadal steroids, neurotransmitter systems, and endogenous
      circadian drive. Both receptor species are present during development, implying
      an ability for these transcription factors to interact with neuronal
      differentiation, growth, and viability, and both receptors appear to regulate
      with age, suggesting relationships between adrenocorticosteroid receptor
      populations and brain aging. Regulation of adrenocorticosteroid receptor mRNA
      expression at the level of polyadenylation and splicing indicates that GR and MR
      biosynthesis is a dynamic process susceptible to numerous classes of information.
      3. Further study of GR and MR biosynthesis at the gene, mRNA, and protein level
      is required to determine the true meaning of the regulatory complexities seen in
      defined neuronal circuits.

PMID- 8252608
TI  - Dexamethasone target sites in the central nervous system and their potential
      relevance to mental illness.
AB  - 1. The topical distribution of tritiated dexamethasone (DEX), a potent synthetic
      glucocorticoid of widespread use in the diagnosis and assessment of mental
      illness, was studied in rat CNS by autoradiography to obtain information on
      potential target sites for feedback and other centrally mediated effects of
      glucocorticoids. 2. The cells of the arcuate nucleus of the hypothalamus and the
      lateral thalamic nuclei displayed the most concentrated nuclear accumulation of
      silver grains. 3. Significant accumulation, exceeding that found in the
      hippocampal formation, also occurred in the cells of the ventromedial,
      periventricular, and paraventricular nuclei of the hypothalamus, the locus
      ceruleus, the nucleus tractus solitarii, and the area postrema, none of which are
      targeted by corticosterone, the native glucocorticoid of the rat. 4. Nuclear
      accumulation of silver grains was prominent in neural and glial cells of the
      cerebral cortex, the olfactory nucleus, the dorsolateral septum, the amygdala,
      the subfornical organ, the lateral parabrachial, medial trapezoid, and dorsal
      reticular nuclei, the nucleus centralis of the raphe, the cerebellum, and
      vascular tissues. 5. The localization of DEX in hypothalamic and brain-stem
      nuclei coincided with that of the glucocorticoid receptor, possibly implicating
      these sites in direct or modulating effects of glucocorticoids in various forms
      of mental disturbance, including depression, anxiety, panic disorders, and
      alcohol withdrawal. 6. The extent to which various CNS regions targeted by DEX
      feature in negative feedback control of adrenocortical secretion remains to be
      defined, as does the site of impaired feedback disclosed by the dexamethasone
      suppression test in psychiatric patients.

PMID- 8252609
TI  - Immunocytochemical localization of glucocorticoid receptors in the spinal cord:
      effects of adrenalectomy, glucocorticoid treatment, and spinal cord transection.
AB  - 1. Studies were performed to determine the changes in immunoreactive (IR) type II
      glucocorticoid receptors of the ventral horn of the spinal cord produced by
      adrenalectomy (ADX), dexamethasone (DEX) treatment, and spinal cord transection
      in rats. 2. These treatments did not significantly affect the number of IR
      neurons of the ventral horn; however, staining intensity was enhanced after ADX
      and decreased following 4 days of DEX. A similar response pattern was observed
      for glial-type cells. 3. In control rats, about half of the ventral horn
      motoneurons were surrounded by immunoreactive glial perineuronal cells. These
      perineuronal cells increased after ADX (77% of counted neurons) and decreased
      following DEX treatment (32%; P < 0.05). 4. Two days after transection, staining
      was intensified in ventral horn motoneurons and glial cells located in the spinal
      cord below the lesion. Immunoreactive perineuronal cells increased to 85% of
      counted neurons, from a value of 66% in sham-operated rats (P < 0.05). 5. These
      findings suggest considerable plasticity of the spinal cord GCR in response to
      changes in hormonal levels and experimental lesions. It is possible that factors
      involved in cell to cell communication with transfer of hypothetical regulatory
      molecules may play roles in GCR regulation and the increased immunoreaction of
      glia associated with neurons following transection and ADX.

PMID- 8252610
TI  - Effects of adrenocortical steroids on long-term potentiation in the limbic
      system: basic mechanisms and behavioral consequences.
AB  - Hippocampal structures are a major target for adrenal steroid hormones, and hence
      these neural regions are some of the most likely mediators of the effects of
      adrenocortical steroids on behavior. Memory disturbance, in particular biasing
      toward negative contents, are part of the symptomatology presented by depressive
      patients. In turn, a sizeable subset of depression also presents with
      hypercortisolemia. Adrenocortical hormones are also known to affect memory
      processes. Hippocampal formation is essential for declarative memory. We thought
      it appropriate then to study the effects of adrenal steroids on long-term
      potentiation, a putative memory mechanism in the hippocampus. Two clearly
      distinguished components of the evoked response to perforant path stimulation can
      be studied in the hippocampus: the excitatory postsynaptic potential (EPSP) which
      denotes the graded depolarization of the somatodendritic region of the neuron and
      the population spike (PS), a manifestation of the all-or-none-discharge of the
      cell action potential. Corticosterone had a significant depressant effect on the
      EPSP component of the evoked response immediately and 15 min after injection.
      Thereafter EPSP amplitudes were within normal values. Corticosterone
      significantly decreased the PS immediately after the train, the component
      remaining low 30 min after the train. 5 alpha-Dihydrocorticosterone (a ring A
      reduced metabolite of corticosterone) significantly reduced the PS component of
      the response at all times after injection. 18-Hydroxydeoxycorticosterone and
      deoxycorticosterone significantly decreased both EPSP and PS components of the
      evoked response from the time of infusion. Contrary to expectation,
      tetrahydrodeoxycorticosterone was ineffective in decreasing and if anything,
      enhanced the development of long-term potentiation. 18-Hydroxydeoxycorticosterone
      21-acetate behaved like vehicle, except for the first 30 min after injection when
      the EPSP was decreased. Allotetrahydroprogesterone decreased all EPSP's values
      and had no effect in the PS development in comparison with vehicle. The
      suggestion is made that the study of steroidal effects on hippocampal LTP can
      serve as a preclinical model of some aspects of depression in a specific subset
      of the disease.

PMID- 8252611
TI  - Neuroprotective actions of glucocorticoid and nonglucocorticoid steroids in acute
      neuronal injury.
AB  - 1. The glucocorticoid steroid methylprednisolone (MP) has been shown to enhance
      chronic recovery after human spinal cord injury when administered in a 24-hr high
      dose regimen beginning within 8 hr. The doses of MP that affect this improved
      recovery have been demonstrated to inhibit posttraumatic spinal cord lipid
      peroxidation (LP), which has been postulated to be a key event in the secondary
      injury-induced degenerative cascade. 2. The molecular mechanism of action of the
      steroid appears to involve intercalation into the cell membrane and blockade of
      the propagation of peroxidative reactions. At a physiological level, the
      inhibition of injury-induced LP has been found to result in an attenuation of
      progressive posttraumatic ischemia and energy failure together with an augmented
      reversal of intracellular calcium accumulation. However, MP also acts directly to
      retard secondary neuronal degeneration as observed in studies showing the
      steroid's ability to slow the anterograde degeneration of experimentally injured
      cat soleus motor nerves. 3. The duplication of this effect by the nonsteroidal
      lipid antioxidant alpha-tocopherol supports the notion that is indeed a
      manifestation of the inhibition of posttraumatic LP. Moreover, the efficacy of MP
      in limiting lipid peroxidation and secondary spinal cord or motor nerve
      degeneration has also been duplicated by a nonglucocorticoid 21-aminosteroid
      tirilazad mesylate (U-74006F), which suggests the independence of the antioxidant
      and glucocorticoid effects of MP.

PMID- 8252612
TI  - Functional implications of brain corticosteroid receptor diversity.
AB  - 1. Corticosteroids readily enter the brain and control gene expression in nerve
      cells via binding to intracellular receptors, which act as gene transcription
      factors. In the rat brain corticosterone binds to mineralocorticoid receptors
      (MRs) with a 10-fold higher affinity than to glucocorticoid receptors (GRs). As a
      consequence, these MRs are extensively occupied under basal resting conditions,
      while substantial GR occupation occurs at the circadian peak and following
      stress. Both receptors are colocalized in most, but not all, hippocampal neurons.
      In addition, some neurons contain aldosterone-selective MRs, if corticosterone is
      enzymatically inactivated. These aldosterone target neurons are presumably
      localized in the anterior hypothalamus, where they underlie central control of
      salt appetite and cardiovascular regulation. 2. The data show that MR- and GR
      mediated effects proceed in a coordinate and often antagonistic mode of action:
      (i) in hippocampus MR activation maintains excitability, while GR occupancy
      suppresses excitability, which is transiently raised by excitatory stimuli; (ii)
      central MRs participate in control of the sensitivity of the neuroendocrine
      stress response system, while GRs are involved in termination of the stress
      response; (iii) MRs in the hippocampus have a role in regulation of behavioral
      reactivity and response selection. GR-mediated effects facilitate storage of
      information. 3. On the basis of these data, we propose that a relative deficiency
      or excess of MR- over GR-mediated neuronal effects may lead to a condition of
      enhanced or reduced responsiveness to environmental influences, alter behavioral
      adaptation, and promote susceptibility to stress. The findings may serve
      development of novel therapeutic strategies for treatment of stress-related brain
      diseases.

PMID- 8252614
TI  - How profilin promotes actin filament assembly in the presence of thymosin beta 4.
AB  - The role of profilin in the regulation of actin assembly has been reexamined. The
      affinity of profilin for ATP-actin appears 10-fold higher than previously
      thought. In the presence of ATP, the participation of the profilin-actin complex
      to filament elongation at the barbed end is linked to a decrease in the steady
      state concentration of globular actin. This surprising effect is made possible by
      the involvement of the irreversible ATP hydrolysis accompanying actin
      polymerization. As a consequence, in the presence of thymosin beta 4 (T beta 4),
      low amounts of profilin promote extensive actin assembly off of the pool of actin
      T beta 4 complex. When barbed ends are capped, profilin simply sequesters
      globular actin. A model is proposed for the function of profilin in actin-based
      motility.

PMID- 8252613
TI  - Adrenal steroids and plasticity of hippocampal neurons: toward an understanding
      of underlying cellular and molecular mechanisms.

PMID- 8252615
TI  - Stepwise assembly of functionally active transport vesicles.
AB  - Budding of COP-coated vesicles (the likely carriers of newly synthesized proteins
      from the endoplasmic reticulum through the Golgi stack) from Golgi cisternae
      requires ADP-ribosylation factor (ARF), coatomer proteins from the cytosol, GTP,
      and fatty acyl-coenzyme A (CoA). The assembly of coated buds on the membranes
      requires coatomer, ARF, and GTP. When palmitoyl-CoA is added, membrane fission
      occurs at the coated bud, releasing coated vesicles. We show that COP-coated
      vesicles can be generated stepwise in vitro and isolated in a functionally active
      form, demonstrating that the minimal set of cytosolic components required for
      their formation as well as principal steps in their assembly have been
      identified.

PMID- 8252616
TI  - The human mutator gene homolog MSH2 and its association with hereditary
      nonpolyposis colon cancer.
AB  - We have identified a human homolog of the bacterial MutS and S. cerevisiae MSH
      proteins, called hMSH2. Expression of hMSH2 in E. coli causes a dominant mutator
      phenotype, suggesting that hMSH2, like other divergent MutS homologs, interferes
      with the normal bacterial mismatch repair pathway. hMSH2 maps to human chromosome
      2p22-21 near a locus implicated in hereditary nonpolyposis colon cancer (HNPCC).
      A T to C transition mutation has been detected in the -6 position of a splice
      acceptor site in sporadic colon tumors and in affected individuals of two small
      HNPCC kindreds. These data and reports indicating that S. cerevisiae msh2
      mutations cause an instability of dinucleotide repeats like those associated with
      HNPCC suggest that hMSH2 is the HNPCC gene.

PMID- 8252617
TI  - HLH proteins, fly neurogenesis, and vertebrate myogenesis.

PMID- 8252618
TI  - Community effects and related phenomena in development.

PMID- 8252619
TI  - The three faces of profilin.

PMID- 8252620
TI  - Braking the cycle.

PMID- 8252621
TI  - The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense
      complementarity to lin-14.
AB  - lin-4 is essential for the normal temporal control of diverse postembryonic
      developmental events in C. elegans. lin-4 acts by negatively regulating the level
      of LIN-14 protein, creating a temporal decrease in LIN-14 protein starting in the
      first larval stage (L1). We have cloned the C. elegans lin-4 locus by chromosomal
      walking and transformation rescue. We used the C. elegans clone to isolate the
      gene from three other Caenorhabditis species; all four Caenorhabditis clones
      functionally rescue the lin-4 null allele of C. elegans. Comparison of the lin-4
      genomic sequence from these four species and site-directed mutagenesis of
      potential open reading frames indicated that lin-4 does not encode a protein. Two
      small lin-4 transcripts of approximately 22 and 61 nt were identified in C.
      elegans and found to contain sequences complementary to a repeated sequence
      element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin-4
      regulates lin-14 translation via an antisense RNA-RNA interaction.

PMID- 8252622
TI  - Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates
      temporal pattern formation in C. elegans.
AB  - During C. elegans development, the temporal pattern of many cell lineages is
      specified by graded activity of the heterochronic gene Lin-14. Here we
      demonstrate that a temporal gradient in Lin-14 protein is generated
      posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated
      by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and
      sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The
      function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae.
      Among the conserved sequences are seven elements that are each complementary to
      the lin-4 RNAs. A reporter gene bearing three of these elements shows partial
      temporal gradient activity. These data suggest a molecular mechanism for Lin-14p
      temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14
      3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.

PMID- 8252623
TI  - Disruption of base pairing between the 5' splice site and the 5' end of U1 snRNA
      is required for spliceosome assembly.
AB  - A short RNA oligonucleotide comprising the 5' splice site consensus sequence
      (5'SS RNA) is sufficient to bind U1 small nuclear ribonucleoprotein particle
      (snRNP) or to induce the association of U2 snRNP and U4-U5-U6 triple snRNP.
      Analysis of the requirements of these interactions demonstrates that the 5'SS RNA
      is recognized independently by at least two different elements during spliceosome
      assembly: the 5' end of U1 snRNA and a component(s) of the U2-U4-U5-U6 snRNP
      complex. Since stable 5'SS RNA-U1 snRNA base pairing prevents interaction of the
      5'SS RNA with U2-U4-U5-U6 snRNP complex, we conclude that disruption of the
      initial base pairing between the 5'SS RNA and the 5' end of U1 snRNA is required
      for subsequent spliceosome assembly.

PMID- 8252624
TI  - Inducibility and negative autoregulation of CREM: an alternative promoter directs
      the expression of ICER, an early response repressor.
AB  - cAMP-responsive element modulator (CREM) expression is tissue specific and
      developmentally regulated. Here we report that CREM is unique within the family
      of cAMP-responsive promoter element (CRE)-binding factors since it is inducible
      by activation of the cAMP signaling pathway. The kinetic of expression is
      characteristic of an early response gene. The induction is transient and cell
      specific, does not involve increased transcript stability, and does not require
      protein synthesis. Significantly, the subsequent decline in CREM expression
      requires de novo protein synthesis. The induced transcript encodes a novel
      repressor, inducible cAMP early repressor (ICER), and is generated from an
      alternative intronic promoter. A cluster of four CREs in this promoter directs
      cAMP inducibility. ICER binds to these elements and thereby represses the
      activity of its own promoter, thus constituting a negative autoregulatory loop.

PMID- 8252625
TI  - The interaction of SV40 small tumor antigen with protein phosphatase 2A
      stimulates the map kinase pathway and induces cell proliferation.
AB  - Interaction with SV40 small tumor antigen (small t) compromised the ability of
      multimeric protein phosphatase 2A to inactivate the mitogen-activated protein
      kinase ERK1 and the mitogen-activated protein kinase kinase MEK1. Transient
      expression of small t in CV-1 cells activated MEK and ERK but did not affect Raf
      activity. Small t stimulated the growth of quiescent CV-1 cells almost as
      effectively as did serum. Coexpression of kinase-deficient ERK2 blocked most, but
      not all, of the proliferation caused by small t. Activation of the mitogen
      activated protein kinase pathway and stimulation of cell growth were dependent on
      the interaction of small t with protein phosphatase 2A. These findings indicate
      that SV40 small t is capable of inducing cell growth through blockade of protein
      phosphatase and deregulation of the mitogen-activated protein kinase cascade.

PMID- 8252626
TI  - High levels of c-rel expression are associated with programmed cell death in the
      developing avian embryo and in bone marrow cells in vitro.
AB  - To determine the physiological processes in which the transcription factor c-Rel
      may act, we have examined its pattern of expression in the avian embryo by in
      situ hybridization. These studies showed that c-rel is expressed ubiquitously at
      low levels and at high levels in isolated cells undergoing programmed cell death
      by apoptosis or autophagocytosis. To further establish a functional link between
      expression of c-rel and cell death, we examined the biological consequences of c
      rel overexpression in vitro. In primary avian fibroblasts, overexpression of c
      rel leads to transformation and dramatic life span extension. In contrast, bone
      marrow cells expressing high levels of c-rel undergo a process of programmed cell
      death displaying features of both apoptosis and autophagocytic cell death. Thus,
      these experiments suggest a critical role for c-rel not only in the control of
      cell proliferation, but also in the induction of cell death.

PMID- 8252627
TI  - The TGF beta homolog dpp and the segment polarity gene hedgehog are required for
      propagation of a morphogenetic wave in the Drosophila retina.
AB  - Development of the Drosophila retina occurs asynchronously; differentiation, its
      front marked by the morphogenetic furrow, progresses across the eye disc
      epithelium over a 2 day period. We have investigated the mechanism by which this
      front advances, and our results suggest that developing retinal cells drive the
      progression of morphogenesis utilizing the products of the hedgehog (hh) and
      decapentaplegic (dpp) genes. Analysis of hh and dpp genetic mosaics indicates
      that the products of these genes act as diffusible signals in this process.
      Expression of dpp in the morphogenetic furrow is closely correlated with the
      progression of the furrow under a variety of conditions. We show that hh,
      synthesized by differentiating cells, induces the expression of dpp, which
      appears to be a primary mediator of furrow movement.

PMID- 8252628
TI  - The segment polarity gene hedgehog is required for progression of the
      morphogenetic furrow in the developing Drosophila eye.
AB  - Cell-type specification in the Drosophila compound eye begins at the
      morphogenetic furrow. The furrow sweeps across the developing eye epithelium and
      is coincident with four classes of cellular events: coordinated changes in cell
      shape, changes in gene expression, synchronization of the cell cycle, and the
      specification of a regular array of ommatidial founder cells. The molecular
      mechanisms that induce these events in the developing eye have hitherto been
      unknown. We identify here a gene specifically required for furrow progression,
      hedgehog (hh). We show that hh expression posterior to the morphogenetic furrow
      is continuously required for its progression. We propose that forward diffusion
      of hh protein induces anterior cells to enter the furrow.

PMID- 8252629
TI  - The Tousled gene in A. thaliana encodes a protein kinase homolog that is required
      for leaf and flower development.
AB  - Mutation at the TOUSLED locus of A. thaliana results in a complex phenotype, the
      most dramatic aspect of which being the abnormal flowers produced in mutant
      plants. tsl flowers show a random loss of floral organs, and organ development is
      impaired. The TSL gene appears to be required in the floral meristem for correct
      initiation of floral organ primordia and for proper development of organ
      primordia. Loss of TSL function also affects flowering time and leaf morphology.
      Using a mutation derived by T-DNA insertion mutagenesis, we have cloned the TSL
      gene and found that it encodes a protein kinase homolog with a novel N-terminal
      domain. This protein kinase gene identifies a novel signaling/regulatory pathway
      used during development in Arabidopsis.

PMID- 8252630
TI  - Alleles of the APC gene: an attenuated form of familial polyposis.
AB  - An attenuated form of familial adenomatous polyposis coli, AAPC, causes
      relatively few colonic polyps, but still carries a significant risk of colon
      cancer. The mutant alleles responsible for this attenuated phenotype have been
      mapped in several families to the adenomatous polyposis coli (APC) locus on human
      chromosome 5q. Four distinct mutations in the APC gene have now been identified
      in seven AAPC families. These mutations that predict truncation products, either
      by single base pair changes or frameshifts, are similar to mutations identified
      in families with classical APC. However, they differ in that the four mutated
      sites are located very close to one another and nearer the 5' end of the APC gene
      than any base substitutions or small deletions yet discovered in patients with
      classical APC.

PMID- 8252631
TI  - Restriction of ocular fundus lesions to a specific subgroup of APC mutations in
      adenomatous polyposis coli patients.
AB  - In humans, alteration of the tumor suppressor gene, APC, causes adenomatous
      polyposis coli, a condition causing predisposition to colorectal cancer. The
      syndrome inconsistently associates characteristic patches of congenital
      hypertrophy of the retinal pigment epithelium (CHRPE). Ocular examination
      revealed that patients expressing CHRPE tend to cluster within specific families.
      The exact APC mutation was identified in 42 unrelated patients. In all cases
      these mutations were predicted to lead to the synthesis of a truncated protein.
      The extent of CHRPE was found to be dependent on the position of the mutation
      along the coding sequence. CHRPE lesions are almost always absent if the mutation
      occurs before exon 9, but are systematically present if it occurs after this
      exon. Thus, the range of phenotypic expression observed among affected patients
      may result in part from different allelic manifestations of APC mutations.

PMID- 8252632
TI  - Abolition of anaphylaxis by targeted disruption of the high affinity
      immunoglobulin E receptor alpha chain gene.
AB  - Mast cells and basophils, which are activated by immunoglobulin E (IgE) and
      allergen, play a prominent role in anaphylaxis. However, they express at least
      three types of IgE receptor, including the high affinity IgE receptor (Fc epsilon
      RI). The relative contribution of these IgE receptors, and possibly other
      receptors such as Fc epsilon RII/CD23 and Mac-2, to the genesis of in vivo
      anaphylaxis is still unclear. To address this question, we have generated Fc
      epsilon RI-deficient mice. These mice appear normal and express a normal number
      of mast cells, but they are resistant to cutaneous and systemic anaphylaxis.
      These data demonstrate that Fc epsilon RI is necessary for the initiation of IgE
      dependent anaphylactic reactions. Therefore, interfering with its function should
      be an effective means of treating allergy, regardless of the allergen
      specificity.

PMID- 8252633
TI  - Autocrine release of angiotensin II mediates stretch-induced hypertrophy of
      cardiac myocytes in vitro.
AB  - Hypertrophy is a fundamental adaptive process employed by postmitotic cardiac and
      skeletal muscle in response to mechanical load. How muscle cells convert
      mechanical stimuli into growth signals has been a long-standing question. Using
      an in vitro model of load (stretch)-induced cardiac hypertrophy, we demonstrate
      that mechanical stretch causes release of angiotensin II (Ang II) from cardiac
      myocytes and that Ang II acts as an initial mediator of the stretch-induced
      hypertrophic response. The results not only provide direct evidence for the
      autocrine mechanism in load-induced growth of cardiac muscle cells, but also
      define the pathophysiological role of the local (cardiac) renin-angiotensin
      system.

PMID- 8252634
TI  - [Biological effects of substances similar to salicylanilides. 3-aryl-2H, 4H
      benz(e)(1,3)oxazine-2, 4-diones and thiosalicylanilides].
AB  - The review paper is the first collected communication about the biological
      activity of 3-aryl-2H,4H-benz(e)(1,3)oxazine-2,4-diones and thiosalicylanilides.
      The substances of the above mentioned structures show a number of biological
      activities (antibacterial, antituberculous, antimycotic, anthelmintic,
      molluscocidal, neuroleptic, analgesic and anti-inflammatory) which can be
      modelled by structural changes. Only very few of them have been hitherto
      introduced into practice as anthelmintic agents, or agents with a special purpose
      (destroying the sea lamprey in Canadian lakes). In the group of 3-aryl-2H,3H
      benz(e)(1,3)-oxazine-2,4-diones, i.e. substances developed from salicylanilides
      by the action of alkyl-chloroformiates, antibacterial activity is reported in
      refs. 3-12, antituberculous activity in refs. 13, 14, antimycotic activity in
      refs. 5, 6, 9, 12, 15, 16, anthelmintic activity in refs. 6,917-20, molluscocidal
      activity in refs. 6, 21, analgesic and anti-inflammatory activity in refs. 22-24,
      herbicidal activity in refs. 25, 26, allergenic activity in ref. 27. In the group
      of salicylanilides, antibacterial activity is reported in refs. 28-37,
      antimycotic activity in refs. 28-36, antiprotozoal activity in ref. 35,
      anthelmintic activity in refs. 28-40, 49, molluscocidal activity in refs. 7, 28
      36. The present paper furthermore sums up the papers concerned with the
      toxicities of the above-mentioned agents. Though the peak of research of the
      groups of the above-mentioned structure was in the 1960s and 1970s, papers
      investigating their biological activity can be encountered also at present.

PMID- 8252635
TI  - [Testing for immunomodulating effects of ethanol-water extracts of the above
      ground parts of the plants Echinaceae (Moench) and Rudbeckia L].
AB  - Ethanolic extracts of aerial parts of the plants Echinacea angustifolia DC,
      Echinacea purpurea L. (Moench), Rudbeckia fulgida var. sullivantii, Boyton et
      Beadle, and Rudbeckia speciosa Wenderoth show immunomodulating activity. The mice
      were treated in vivo for 5 days and the activity was tested for and observed on
      day 7. An immunostimulatory effect was observed on the phagocytic, metabolic and
      bactericidal activities of peritoneal macrophages. The ethanolic extracts of both
      Echinacea plants also increased the total weight of the spleens as compared to
      the effect of the Rudbeckia plants and the control group which received saline.

PMID- 8252636
TI  - Reaching for the ring: the study of mitochondrial genome structure.
AB  - The linear molecules that comprise most of the mitochondrial DNA (mtDNA) isolated
      from most organisms result from the artifactual degradation of circular genomes
      that exist within mitochondria. This view has been adopted by most investigators
      and is based on DNA fragment mapping data as well as analogy to the genome-sized
      circular mtDNA molecules obtained in high yield from animals. The alternative
      view that linear molecules actually represent the major form of DNA within
      mitochondria is supported by two observations; (1) over a 1000-fold range of
      genome size among fungi and plants we find the same size distribution of linear
      mtDNA molecules, and (2) linear mtDNA molecules much larger than genome size can
      be found for some fungi and plants. The circles that represent only a small
      fraction of the mtDNA obtained from most eukaryotes could be optional sequence
      forms unimportant for mitochondrial function; they may also participate in mtDNA
      replication. The circles might result from incidental recombination events
      between directly repeated sequences within or between tandemly arrayed genome
      units on linear mtDNA molecules.

PMID- 8252637
TI  - Evidence for a gene cluster involving trichothecene-pathway biosynthetic genes in
      Fusarium sporotrichioides.
AB  - Two overlapping cosmid clones (Cos1-1 and Cos9-1) carrying the Tox5 gene were
      isolated from a library of F. sporotrichioides strain NRRL 3299 genomic DNA.
      These cosmids were used to transform three T-2 toxin-deficient mutants that are
      blocked at different steps in the trichothecene pathway. Both cosmids restored T
      2 toxin production to Tox3-1- or Tox4-1- mutants but neither restored T-2 toxin
      production to a Tox1-2- mutant. The production of T-2 toxin by the complemented
      Tox3-1- and Tox4-1- mutants, as well as the production of diacetoxycirpenol by
      the cosmid-transformed Tox1-2- mutant, were 2- to 10-fold higher than in strain
      NRRL 3299. In addition, those transformants carrying Cos9-1 produced
      significantly higher levels of trichothecenes than transformants carrying Cos1-1.
      Two different DNA fragments (FSC13-9 and FSC14-5), representing the region of
      overlap between the cosmid clones, were isolated. These fragments specifically
      complemented either the Tox3-1- mutant (FSC14-5) or the Tox4-1- mutant (FSC13-9).
      The trichothecene-production phenotype of these transformants was similar to NRRL
      3299. These results suggest that two or more genes involved in the biosynthesis
      of trichothecenes are closely linked to Tox5.

PMID- 8252638
TI  - Isolation and characterization of novel genes which are expressed during the very
      early stage of zygote formation in Chlamydomonas reinhardtii.
AB  - We have obtained five cDNA clones which are complementary to transcripts that
      accumulate specifically during the early stage of zygote formation in
      Chlamydomonas reinhardtii. Based on the time-course of transcript accumulation of
      their corresponding genes, these clones were classified into two groups: an early
      expression group (three clones; pZS102-1, pZS102-69, pZS1802) and a late
      expression group (two clones; pZS1860 and pZS1886). The levels of transcripts in
      the former group reached a maximum 30 min after the onset of mating, whereas
      those in the latter group peaked at 3 h. The addition of 10 micrograms/ml of
      cycloheximide reduced the decline in the levels of transcripts, except in the
      transcript corresponding to pZS102-69. Two clones, pZS102-1 and pZS102-69,
      contained highly-homologous predicted open-reading frames, and were judged to be
      cDNAs for two members of a novel gene family. These genes were referred to as
      zys1A and zys1B, respectively.

PMID- 8252639
TI  - A multitude of suppressors of group II intron-splicing defects in yeast.
AB  - Disruption of the nuclear MRS2 gene (mrs2-1 mutation) causes a strong pet-
      phenotype in strains with mitochondrial group II introns, and a leaky pet-
      phenotype in strains without group II introns. MRS3 and MRS4, the genes for two
      mitochondrial-solute carrier proteins, can suppress both phenotypes when present
      in high-copy-number plasmids. In order to search for further multicopy
      suppressors of the mrs2-1 mutant phenotype, an yeast genomic DNA library, MW90,
      was constructed in YEp351 from a strain deleted for the MRS2, MRS3 and MRS4
      genes. Ten different Sau3A DNA fragments that act as multicopy suppressors of the
      mrs2-1 respiratory-deficient phenotype were isolated from this library. Some of
      the newly isolated genes suppress the pet- phenotypes of mrs2-1 cells in strains
      with and without mitochondrial group II introns. Other genes, however, are
      suppressors only for the mitochondrial intron-less strains. This supports the
      notion that the MRS2 gene product is bifunctional i.e., it is essential for the
      splicing of group II introns and is also involved in processes of mitochondrial
      biogenesis other than RNA splicing.

PMID- 8252640
TI  - Molecular cloning of the PEL1 gene of Saccharomyces cerevisiae that is essential
      for the viability of petite mutants.
AB  - The PEL1 gene of Saccharomyces cerevisiae is essential for the cell viability of
      mitochondrial petite mutants, for the ability to utilize glycerol and ethanol on
      synthetic medium, and for cell growth at higher temperatures. By tetrad analysis
      the gene was assigned to chromosome III, centromere proximal of LEU2. The PEL1
      gene has been isolated and cloned by the complementation of a pel1 mutation. The
      molecular analysis of the chromosomal insert carrying PEL1 revealed that this
      gene corresponds to the YCL4W open reading frame on the complete DNA sequence of
      chromosome III. The putative Pel1 protein is characterized by a low molecular
      weight of approximately 17 kDa, a low codon adaptation index, and a high leucine
      content.

PMID- 8252641
TI  - A tRNA(Ser)(UCN) gene in Artemia salina mitochondrial DNA: a case of mistaken
      identity.
AB  - We have sequenced a segment of mitochondrial DNA (mtDNA) of a crustacean, the
      brine shrimp, Artemia salina, that includes 3' end-proximal regions of the genes
      for subunit 1 of the NADH dehydrogenase complex (ND1) and cytochrome b (Cyt b).
      From our data we conclude that in this mtDNA, as in the mtDNAs of Drosophila
      species, a tRNA(Ser)(UCN) gene separates the ND1 and Cyt b genes. This is
      contrary to an earlier report that the A. salina ND1 and Cyt b genes are
      immediately adjacent to each other.

PMID- 8252642
TI  - Characterization of expression of a mitochondrial gene region associated with the
      Brassica "Polima" CMS: developmental influences.
AB  - The mitochondrial genome of the Polima (pol) male-sterile cytoplasm of Brassica
      napus contains a chimeric 224-codon open reading frame (orf224) that is located
      upstream of, and co-transcribed with, the atp6 gene. The N-terminal coding region
      of orf224 is derived from a conventional mitochondrial gene, orfB, while the
      origin of the remainder of the sequence is unknown. We show that an apparently
      functional copy of orfB is present in the pol mitochondrial genome, indicating
      that the pol CMS is not caused by the absence of an intact, expressed orfB gene.
      The 5' termini of orf224/atp6 transcripts present in both sterile and fertility
      restored (Rf) pol cytoplasm plants are shown to map to sequences resembling
      mitochondrial transcription-initiation sites, whereas the 5' termini of two
      transcripts specific to restored lines map to sequences which resemble neither
      one another nor mitochondrial promoter motifs. It is suggested that the complex
      orf224/atp6 transcript pattern of Rf plants is generated by a combination of
      multiple transcription initiation and processing events and that the nuclear
      restorer gene acts to specifically alter orf224/atp6 transcripts by affecting RNA
      processing. Northern analyses demonstrate that the effect of the restorer gene on
      orf224/atp6 transcripts is not tissue or developmental-stage specific. However,
      the expression of the atp6 region is developmentally regulated in pol plants,
      resulting in decreased levels of monocistronic atp6 transcripts in floral tissue
      relative to seedlings. It is suggested that this developmental regulation may be
      related to the absence of overt phenotypic effects of the CMS mutation in
      vegetative tissues.

PMID- 8252643
TI  - Genes for ribosomal proteins S3, L16, L5 and S14 are clustered in the
      mitochondrial genome of Brassica napus L.
AB  - We have cloned and sequenced an 8.9-kb mitochondrial-DNA fragment from rapeseed
      (Brassica napus L.). The nucleotide sequence indicates a gene cluster that
      encodes four ribosomal proteins (S3, L16, L5, S14), two tRNA genes (trnD, trnK),
      and the 5' region of the cob gene. The arrangement of these seven genes is trnD
      trnK-rps3-rpl16-rpl5-rps14-cob. The rps3 and rpl16 frames overlap by 131 bp. The
      rpl5 and rps14 genes are separated by a 4-bp spacer. A 1474-basepair intron is
      located in the rps3 gene. The tRNA(Asp) gene (trnD) is very similar to the
      corresponding gene from chloroplasts (cp-like-tRNA(Asp)). Gene-specific probes
      for each ribosomal protein gene, and for the cp-like-trnD, trnK and cob genes,
      hybridized to a common pre-mRNA of an estimated size of 10 kilobases, indicating
      that these seven genes may be expressed as a single transcription unit. The rps3
      rpl16-rpl5-rps14 region of B. napus mtDNA may function as a ribosomal operon,
      similar to the S10 and SPC operons of Escherichia coli and to the ribosomal
      protein operon of the chloroplast genome from Euglena gracilis.

PMID- 8252644
TI  - Mitochondrial genome of the dimorphic zygomycete Mucor racemosus.
AB  - Mitochondria were isolated from the dimorphic zygomycete Mucor racemosus by
      differential centrifugation. DNA from the organelles was purified by cesium
      chloride-ethidium bromide isopycnic centrifugation. Examination of the
      mitochondrial DNA by electron microscopy revealed a circular chromosome
      approximately 63.8 kbp in circumference. The chromosome was digested with
      restriction endonucleases and the resulting DNA fragments were separated by
      agarose-gel electrophoresis. Electophoretic mobilities and stoichiometry of the
      fragments indicated a mixed population of mtDNA molecules each with a size of
      about 63.4 kbp. Physical maps were constructed from analyses of fragments
      generated in single and double restriction digests and from the hybridization of
      fragments to probes for the large and small mitochondrial rRNA genes from
      Saccharomyces cerevisiae. The Mucor mitochondrial chromosome was found to exist
      in the form of two flip-flop isomers with inverted repeat sequences encoding both
      rRNA genes.

PMID- 8252646
TI  - A chloroplast DNA mutational hotspot and gene conversion in a noncoding region
      near rbcL in the grass family (Poaceae).
AB  - The noncoding DNA region of the chloroplast genome, flanked by the genes rbcL and
      psaI (ORF36), has been sequenced for seven species of the grass family (Poaceae).
      This region had previously been observed as a hotspot area for length mutations.
      Sequence comparison reveals that short duplications, probably resulting from
      slipped-strand mispairing, account for many small length differences between
      sequences but that major mutational hotspots are localized in three small areas,
      two of which show potential secondary structure. Mutation in one of these
      hotspots appears to be a result of more complex recombination events. All seven
      species contain a pseudogene for rpl23 and evidence is presented that this
      pseudogene is being maintained by gene conversion with the functional gene.
      Different transition/transversion biases and AT contents between the pseudogene
      and the surrounding noncoding sequences are noted. In the subfamily Panicoideae
      there is a deletion in which almost 1 kb of ancestral sequence, including the 3'
      end of the rpl23 pseudogene, has been replaced by a non-homologous 60-base
      sequence of unknown origin. Two other deletions of almost the same region have
      occurred in the grass family. The deleted noncoding region has mutational and
      compositional properties similar to the rbcL coding sequence and the rpl23
      pseudogene. The three independent deletions, as well as the pattern of mutation
      in the localized hotspots, indicate that such noncoding DNA may be misleading for
      studies of phylogenetic inference.

PMID- 8252645
TI  - Biolistic transformation of Trichoderma harzianum and Gliocladium virens using
      plasmid and genomic DNA.
AB  - Biolistic (biological ballistic) and protoplast-mediated procedures were compared
      as methods for transforming strains of Gliocladium virens and Trichoderma
      harzianum. For biolistic transformation, conidia were bombarded using a helium
      driven biolistic device to accelerate M5 tungsten particles coated with plasmid
      or genomic DNA. DNA from either source contained a bacterial hygromycin B
      resistance gene (hygB) as a dominant selectable marker. The same sources of DNA
      were also used to transform protoplasts using a standard polyethylene glycol
      CaCl2 protoplast fusion protocol. Hygromycin B-resistant (HygBR) transformants
      were recovered from all strains, methods, and DNA sources except for genomic DNA
      used with the protoplast method. The biolistic procedure was technically simpler,
      and increased transformation frequency and genetic stability in the progeny as
      compared with the protoplast-mediated transformation. Southern analysis of
      homokaryotic HygBR progenies showed that the transforming sequences were
      integrated into the genome of the recipient strains, and apparently were
      methylated. This is the first study presenting detailed results on biolistic
      transformation of a filamentous fungus.

PMID- 8252647
TI  - Sequence analysis of a Papaver somniferum L. mitochondrial DNA fragment promoting
      autonomous plasmid replication in Saccharomyces cerevisiae and Kluyveromyces
      lactis.
AB  - The minimal fragment of mitochondrial DNA from Papaver somniferum L. (poppy) able
      to promote autonomous plasmid replication in the yeast Saccharomyces cerevisiae
      was sequenced. Sequence analysis of the 917-bp MK4/8 DNA fragment revealed a high
      AT content, and the presence of two 12-bp sequences differing from the ARS core
      consensus of S. cerevisiae only by a T and C insertion, respectively. The
      mitochondrial insert contains a further six 11-bp sequences with one mismatch to
      the S. cerevisiae core consensus, more then 20 related sequences with two base
      pair exchanges, numerous direct and inverted repeats, and many copies of a
      sequence motif called the ARS box. The original 4.2-kb mitochondrial DNA
      fragment, as well as the minimal 917-bp subfragment in vector pFL1-E (a variant
      of YIP5, lacking an origin of replication in yeast), were then tested for their
      ability to replicate autonomously in another fungus, Kluyveromyces lactis.

PMID- 8252648
TI  - [Diagnostic imaging methods in neonates with diseases of the urinary tract].
AB  - The actually used examination algorithm of imaging methods was checked in 35
      neonates examined in the course of two years (1991 and 1992) on account of
      suspected diseases of the urinary pathways. It involved sonographic examination
      of 28 children, voiding cystourethrography (34x) and intravenous urography (18x).
      Ascendent pyelography and irrigography were performed three times, one neonate
      was examined by computed tomography. The procedure used as a basic sonographic
      prenatal screening in 11 children, in 20 clinical suspicion of disease of the
      urinary pathways, and four neonates were examined on account of an anorectal
      malformation or abnormality of the external genitalis. The most frequent finding-
      in 18 children--was hydronephrosis. It was associated with signs of subrenal
      obstruction (8x), with ren duplex (5x) and with a megaureter (6x). The
      association of the sonographic finding of dilatation of the intrarenal urinary
      pathways with absent contrast filling during excretory urography was observed in
      a child with hydronephrosis and subrenal obstruction and in four children with a
      multicystic dysplastic kidney. In individual cases the authors detected a valve
      of the posterior urethra, a sigmoid-vesical fistula, agenesis of the penis and
      stenosis of the urethra. Eleven neonates had a normal findings of the urinary
      tract.

PMID- 8252649
TI  - [Long-term follow-up of the quality of life in children after surgery for
      vascular compression of the respiratory tract].
AB  - The aim of this study is the analysis of long-term results of surgery for
      vascular airway compression. Out of those operated within last 14 years at our
      institution, thirty two have a longer than five years follow up, being now 9.1 +/
      3.0 years following surgery. All are in excellent clinical condition. One
      quarter of patients show occasional stridor and one third frequent respiratory
      infections. Eighty percent have some lung function abnormality, 72% features of
      central airways obstruction. Pulmonary perfusion scintigraphy demonstrated in 19%
      asymmetric pulmonary blood flow. Magnetic resonance imaging showed relationship
      between vessels and airways. Although long-term outcome of surgery for vascular
      airway compression is excellent, high percentage of pathologic lung functions is
      of concern and substantiates the need for close long-term follow-up.

PMID- 8252650
TI  - [Extracorporeal membrane oxygenation. Initial experience at an ECMO center. 1].
AB  - The authors describe their initial experience, organization, and problems
      associated with the development of an EMCO centre. Its main activities are those
      of a neonatal ECMO centre (to a smaller extent paediatric ECMO and ECCO2R-LF PPV
      of adults) during the first 4 months of its existence. During the period the ECMO
      centre was contacted in 10 instances. The referring department indicated the ECMO
      centre correctly in six instances. However, at least in two instances too late
      and the patients died (during priming of the ECMO circuit or transport could not
      be implemented because of the critical condition). In two instances, however, the
      ECMO staff failed as it was unable to ensure a minimum of seven days of safe
      operation of ECMO and therefore ECMO was not provided. Based on this experience
      the authors present an organizational model of the ECMO unit which is formed ad
      hoc when needed and comprises specialists of various professions from the sphere
      of emergency medicine. The main purpose of the present paper is to inform
      referring departments on the indications, selection criteria, contraindications
      of ECMO in neonates and children and to ensure thus not only smooth communication
      between the ECMO centre and the referring department but in the first place early
      referral to the ECMO centre at a time when transport is not yet a problem.

PMID- 8252651
TI  - [Relation between retinopathy and glucose compensation in diabetic children and
      adolescents].
AB  - The fundus of the eye was examined in 302 children and adolescents with insulin
      dependent diabetes (mean age 14.2 years, SD 3.60, mean duration of diabetes 6.4
      years, SD 3.83) by prolonged chromato-ophthalmoscopy and the finding was
      classified according to the authors' own extended classification of diabetic
      retinopathy. In 295 patients the authors assessed the mean value of glycosylated
      protein during the period of 3-6 months before assessment of the retina. When
      these values were compared with the retinal findings, a statistically highly
      significant relationship of retinopathy and the glucose compensation of diabetes
      was found (p < 0.001). The increase of the mean glycoprotein value during
      adolescence, as compared with the prepubertal period, was also statistically
      significant, while adolescents without retinopathy had lower mean glycoprotein
      values as compared with the group as a whole.

PMID- 8252652
TI  - [Evaluation of the functional status of the CNS using evoked potentials and EEG].
AB  - The authors present an account on hitherto little used electrophysiological
      methods for the evaluation of the functional state of the brain and on the
      possibility to use the results of these examinations for prognostic purposes in
      therapeutic care of patients with impaired consciousness. They recommend the use
      of a mobile technique capable to ensure EEG monitoring, examination of the basic
      modalities of evoked potentials (visual, auditory and somatosensory) at the
      bedside. The practical results of these examinations are demonstrated on case
      histories of patients treated at intensive care units for neonates. The asset is
      the relatively reliable evaluation of the actual condition of the brain and the
      possibility to assess the most probable development of the patient's clinical
      condition.

PMID- 8252653
TI  - [SIDS--a retrospective study in Slovakia].
AB  - This is an analysis of 102 cases of SIDS from retrospective studies in the Zilina
      and Senica districts. The incidence of SIDS in the Zilina district was 2.04/1000
      (period 1969-1978) and 1.04/1000 (period 1980-1984). The incidence of SIDS in the
      Senica district was 0.82/1000 (period 1979-1990). According to preliminary
      results of the epidemiological study of SIDS in Slovakia (1991) the incidence is
      only 0.89/1000 which amounts, however, to 23.1% of the post-neonatal mortality.
      In the investigation nine indicators were evaluated: age at the time of death,
      morbidity before death, place of death, education of mother, position of infant
      at time of death, birth weight succession of child in family. The assembled
      results were compared with data in the literature. Because of similar results it
      is assumed that the following risk factors participate in the incidence of SIDS:
      age (2-4 months), time between midnight and 6 a.m., low socio-economic status of
      family, lower education of mother, incidence of SIDS in the family, short
      interval between childbirths, prone position during sleep, succession of child in
      family (third or subsequent), effect of smoking. The investigation did not
      confirm as risk factors a lower birth weight and inadequate postnatal adaptation.
      In the conclusions some possible ways of prevention are outlined.

PMID- 8252654
TI  - [Anomalies in the development of the sinus venosus as a probable cause of heart
      rhythm disorders and fetal hydrops].
AB  - Prenatal ultrasonic examination during the 28th week of gestation revealed a
      transient disorder of the cardiac rhythm in the foetus. Subsequently repeated
      echocardiographic examinations confirmed foetal hydrops which together with signs
      of EP gestosis of the mother was an indication to terminate pregnancy during the
      29th week by Caesarean section. In the severely hydropic male foetus in the
      enlarged anterior wall of the right atrium an atypical vascular canal was found
      which was in the close vicinity of the sinoatrial node. The latter most probably
      caused intermittent intrauterine supraventricular tachycardia in a heart with a
      normal configuration in other respects.

PMID- 8252655
TI  - [Low-output lasers in pediatrics].

PMID- 8252656
TI  - [The Castillo-Morales method in children with orofacial hypotonia].
AB  - Recently great attention is paid to hypotonia of the orofacial region because
      this disorder is a great handicap for mentally normal children. In the submitted
      paper the authors demonstrate treatment of a girl who suffered from hypotonia of
      the orofacial region with hypersalivation to the age of four years. After
      intensive therapy complete normalization of this developmental defect was
      achieved.

PMID- 8252657
TI  - [Acute pain in childhood. 1. Underestimation of pain in children].

PMID- 8252658
TI  - [Acute pain in childhood. 2. Pharmacologic management of pain in children].

PMID- 8252659
TI  - [Catastrophic conditions in children].

PMID- 8252660
TI  - Molecular genetics of heart, lung, and blood diseases. The shape of things to
      come.

PMID- 8252661
TI  - Saving lives through tax policy.

PMID- 8252662
TI  - Benefit of adding low molecular weight heparin to the conventional treatment of
      stable angina pectoris. A double-blind, randomized, placebo-controlled trial.
AB  - BACKGROUND: Patients with chronic coronary artery disease exhibit a
      dysfunctioning endothelium, which may be responsible for exercise-induced
      platelet activation and expression of a procoagulant moiety. In this study, we
      evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin)
      in patients with stable angina pectoris. METHODS AND RESULTS: According to a
      double-blind, randomized, placebo-controlled trial, 29 patients with stable
      exercise-induced angina pectoris and angiographically proven coronary artery
      disease received a single daily subcutaneous injection of Parnaparin or placebo
      on top of aspirin and conventional antianginal medication over 3 months. Patients
      randomized to Parnaparin showed a significant decrease in the fibrinogen level (P
      = .035) and an improvement in both the time to 1-mm ST segment depression (P =
      .008) and the peak ST segment depression (P = .015). The Canadian Cardiovascular
      Society class for angina pectoris was also improved by Parnaparin (P = .016).
      Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas
      thrombin-induced aggregation was reduced (P = .0001). The bleeding time was
      slightly prolonged, but this was not associated with any significant bleeding.
      CONCLUSIONS: Patients with stable angina pectoris may be treated with Parnaparin
      in addition to aspirin and conventional antianginal medication. Side effects are
      negligible, and compliance is excellent.

PMID- 8252663
TI  - Coronary heart disease case fatality in four countries. A community study. The
      Acute Myocardial Infarction Register Teams of Auckland, Augsburg, Bremen,
      FINMONICA, Newcastle, and Perth.
AB  - BACKGROUND: Community-based registers participating in the MONICA Project of the
      World Health Organization show markedly different attack and death rates of
      coronary heart disease. This variation is a function of both the incidence and
      case fatality occurring within countries. The contribution of case fatality to
      the international variation in coronary heart disease mortality rates is not well
      understood. METHODS AND RESULTS: The register data from eight study populations-
      Augsburg and Bremen in Germany, Auckland in New Zealand, Perth and Newcastle in
      Australia, and North Karelia, Kuopio, and Turku/Loimaa in Finland--were compared.
      All patients with definite myocardial infarction or coronary death aged 35 to 64
      years occurring in the study populations in 1985 through 1989 are the basis for
      the case fatality calculations by different definitions: 28-day case fatality for
      all cases, for hospitalized cases, and for hospitalized 24-hour survivors; out-of
      hospital case fatality; and 24-hour case fatality for hospitalized cases.
      Differences in case fatality were much smaller than differences in attack and
      mortality rates in these populations. About two thirds of deaths occurred before
      the patients reached a hospital. The 28-day case fatality ranged from 37% for men
      in Perth to 58% for women in Augsburg. Among those who reached the hospital
      alive, 28-day case fatality was 13% to 27% for men and 20% to 35% for women. In
      those who survived 24 hours from the onset of symptoms, 28-day case fatality was
      8% to 17% for men and 12% to 26% for women. CONCLUSIONS: Differences in case
      fatality were not associated with differences in coronary mortality rates between
      these populations. As most deaths occurred before reaching a hospital,
      opportunities for reducing case fatality through improved hospital care are
      limited. This emphasizes the primary role of prevention in reducing coronary
      death rates.

PMID- 8252664
TI  - The role of transesophageal echocardiography in identifying anomalous coronary
      arteries.
AB  - BACKGROUND: The study objective was to evaluate the role of transesophageal
      echocardiography in identifying the origin of anomalous coronary arteries and
      confirming their course in relation to the great vessels. The diagnosis of
      coronary anomalies is made by angiography. The anomalous left main artery with a
      course between the pulmonary artery and the aorta has been associated with
      myocardial infarction and sudden death. The course of these anomalous coronary
      arteries is difficult to demonstrate by angiography alone. METHODS AND RESULTS:
      Nine patients with angiographically confirmed anomalous coronary arteries were
      studied by transesophageal echocardiography with color flow Doppler. The abnormal
      origin of the anomalous coronary arteries was confirmed by transesophageal
      echocardiography in all nine patients. In four patients, the left main coronary
      artery originated from the right sinus of Valsalva. In all of these patients,
      transesophageal echocardiography demonstrated the course of the anomalous left
      main coronary artery between the aorta and pulmonary artery better than
      angiography. Other anomalies that were visualized included two patients with
      origin of the right coronary arteries from the left aortic sinus, one patient
      with origin of the left anterior descending from the right sinus, one patient
      with origin of circumflex from the right sinus, and one patient with origin of
      the left main coronary artery from the pulmonary artery. CONCLUSIONS:
      Transesophageal echocardiography is a useful noninvasive test for diagnosing
      anomalous origin of the coronary arteries. Furthermore, it is a valuable adjunct
      to angiography in demonstrating the abnormal course of the left main coronary
      artery interposed between the aorta and the pulmonary artery, a potentially life
      threatening entity.

PMID- 8252665
TI  - The role of nitric oxide in endothelium-dependent vasodilation of
      hypercholesterolemic patients.
AB  - BACKGROUND: Patients with hypercholesterolemia have a reduced response to
      endothelium-dependent vasodilators. However, the regulatory function of the
      endothelium on vascular tone is mediated through the release of several
      vasoactive substances; therefore, a reduced response to endothelium-dependent
      agents does not identify which of the factors released by the endothelium is
      involved in this abnormality. METHODS AND RESULTS: To investigate the role of
      nitric oxide in the endothelium-dependent vasodilation in hypercholesterolemia,
      we studied the effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of
      endothelial nitric oxide synthesis, on basal vascular tone and on the responses
      to acetylcholine, an endothelium-dependent vasodilator, and to sodium
      nitroprusside, a direct smooth muscle dilator. The study included 33
      hypercholesterolemic patients (17 men; 51 +/- 8 years; plasma cholesterol, > or =
      240 mg/dL) and 23 normal controls (12 men; 48 +/- 7 years; plasma cholesterol, <
      210 mg/dL). Drugs were infused into the brachial artery, and the response of the
      forearm vasculature was measured by strain-gauge plethysmography. Basal blood
      flow and vascular resistance were similar in hypercholesterolemic patients and
      normal controls (3.1 +/- 1 versus 2.6 +/- 0.8 mL/min per 100 mL and 32.1 +/- 13
      versus 36.1 +/- 12 mm Hg/mL-1.min-1.100 mL-1, respectively). The reduction in
      basal blood flow and increase in vascular resistance produced by L-NMMA were not
      significantly different between the two groups. L-NMMA markedly blunted the
      response to acetylcholine in normals (maximum flow decreased from 16.4 +/- 8 to
      7.0 +/- 3; P < .005); however, the arginine analogue did not significantly modify
      the response to acetylcholine in the hypercholesterolemic patients (maximum flow,
      11.1 +/- 8 versus 10.0 +/- 8). L-NMMA did not modify the vasodilator response to
      sodium nitroprusside in either controls or patients. CONCLUSIONS: These findings
      indicate that hypercholesterolemic patients have a defect in the bioactivity of
      nitric oxide that may explain their impaired endothelium-dependent vascular
      relaxation.

PMID- 8252666
TI  - Prognosis after the onset of coronary heart disease. An investigation of
      differences in outcome between the sexes according to initial coronary disease
      presentation.
AB  - BACKGROUND: Differences exist between men and women in prognosis after the onset
      of coronary heart disease (CHD). METHODS AND RESULTS: All Framingham Heart Study
      subjects with the onset of clinically apparent coronary disease from 1951 through
      1986 were studied to compare prognosis in men and women according to CHD
      presentation. Coronary disease presentations included angina, coronary
      insufficiency (unstable angina), recognized myocardial infarction, unrecognized
      myocardial infarction, and coronary death. Less than 1% of subjects were lost to
      follow-up for overall mortality. Cox modeling was used to examine the sex
      differences in outcome for each coronary presentation. New nonfatal coronary
      disease developed in 750 men (mean age, 63 years) and 583 women (mean age, 67
      years). After onset of angina, men were at greater risk than women for myocardial
      infarction (hazards ratio [HR], 2.20; 95% confidence interval [CI], 1.45 to 3.34)
      and coronary death (HR, 2.11; 95% CI, 1.32 to 3.36) after adjustment for age and
      coronary disease risk factors. After a recognized myocardial infarction, there
      was a trend toward greater risk for overall mortality in women than men after
      adjustment for age and risk factors (HR, 0.75; 95% CI, 0.53 to 1.08). In
      contrast, after an unrecognized myocardial infarction, men were at increased risk
      for death compared with women (HR, 2.01; 95% CI, 1.28 to 3.15). CONCLUSIONS:
      Women fare at least as poorly as men after recognized myocardial infarction,
      whereas women have a more favorable outlook than men after the onset of angina or
      unrecognized myocardial infarction. The favorable outcome in women after angina
      and unrecognized myocardial infarction is due, in part, to greater
      misclassification of these coronary events in women than in men.

PMID- 8252667
TI  - Tailored thrombolytic therapy. A perspective.
AB  - BACKGROUND: In contrast with current standard regimens, it seems more appropriate
      to tailor thrombolytic therapy to individual patient characteristics. A proposed
      model for such tailored therapy is based on individual assessment of benefits and
      risks of thrombolytic therapy, taking into account the response of individual
      patients to the therapy given. METHODS AND RESULTS: Potential benefits of
      thrombolysis in individual patients can be predicted by use of demographic
      patient characteristics (age, sex, history of previous infarction) together with
      indicators of the ischemic area at risk (total ST segment deviation) and
      treatment delay. Using these parameters, the number of "lives saved" by
      thrombolytic therapy for specific patient characteristics can be estimated.
      Similarly, the risk of intracranial hemorrhage during thrombolytic therapy can be
      estimated from the patient's age, blood pressure at admission, and body weight.
      Depending on benefit/risk estimates, a choice can be made between regimens with
      high, medium, or modest thrombolytic efficacy. Continuous multilead ECG ischemia
      monitoring and rapid assays of myocardial proteins in serum can be used to assess
      the occurrence or absence of reperfusion and to detect signs of reocclusion. Such
      data help to decide whether thrombolytic therapy should be continued or
      intensified or might be discontinued in individual patients before the total
      standard dose has been administered. Such tailored reduction of the total
      thrombolytic dose will reduce the risk for bleeding complications in some of the
      patients. CONCLUSIONS: The concept of tailoring thrombolytic therapy and the
      models presented for benefit/risk assessment should be tested in clinical studies
      and may subsequently help the physician to select the optimal approach in
      individual patients.

PMID- 8252668
TI  - Ventricular arrhythmias in trials of thrombolytic therapy for acute myocardial
      infarction. A meta-analysis.
AB  - BACKGROUND: Although thrombolytic therapy reduces long-term mortality in acute
      myocardial infarction, many clinicians remain concerned about an increased risk
      of ventricular arrhythmias associated with the use of these agents. METHODS AND
      RESULTS: To determine whether thrombolytic therapy increases the risk of
      ventricular tachyarrhythmias and whether an increase in arrhythmias could be
      responsible for the increased mortality seen in the first 24 hours after lytic
      therapy, we performed a meta-analysis of 15 randomized trials of thrombolysis in
      acute myocardial infarction in which the odds of developing in-hospital
      ventricular fibrillation (VF) and ventricular tachycardia (VT) in patients
      receiving thrombolysis was compared with that of patients receiving placebo. For
      trials that reported the incidence of VF during the first 6 hours after
      thrombolysis, the summary odds ratio for developing VF in the thrombolytic group
      was 0.98 (95% confidence interval [CI], 0.6 to 1.6; P = .94). For trials that
      reported the incidence of VF during the first hospital day, the summary odds
      ratio for developing VF was 1.00 (95% CI, 0.85 to 1.2; P = .95). The summary odds
      ratio for the development of VF at any time during hospitalization in the
      thrombolytic group was 0.83 (95% CI, 0.76 to 0.90; P < .0001). In trials that
      reported the incidence of VT any time during hospitalization, the summary odds
      ratio for the development of VT in the thrombolytic group was 1.34 (95% CI, 1.15
      to 1.55; P < .0001). CONCLUSIONS: The likelihood of developing VF in the early
      hours after thrombolysis for acute myocardial infarction is similar in patients
      receiving thrombolytics or placebo. However, throughout the hospital course, the
      risk of VF is greater in patients receiving placebo, whereas the risk of VT is
      higher in patients receiving thrombolysis.

PMID- 8252669
TI  - Determinants of the prognosis after a first myocardial infarction in a migrant
      Japanese population. The Honolulu Heart Program.
AB  - BACKGROUND: Although numerous studies have been published on the prognostic
      assessment of myocardial infarction, little is known about determinants of the
      prognosis after a first myocardial infarction, especially regarding the role of
      standard risk factors for coronary heart disease (CHD) measured before the
      development of myocardial infarction. METHODS AND RESULTS: In a prospective study
      of CHD among men of Japanese ancestry living in Hawaii, 457 patients with a first
      myocardial infarction (age range, 46 to 84 years) were identified during 20 years
      of follow-up. The relations of clinical variables and CHD risk factors to
      mortality in early (< 30 days) and two stages of late (30 days to 5 years and 5
      to 10 years) periods after myocardial infarction in these patients were
      investigated. In multivariate analyses using logistic regression models (for
      early mortality) and Cox regression models (for late mortality), age at
      myocardial infarction and severe complications (Killip classes 3 and 4) were
      independent predictors of both early and late mortality (up to 5 years after
      myocardial infarction). In addition, ventricular arrhythmias predicted only early
      mortality, whereas anterior myocardial infarction, radiological evidence of
      cardiomegaly and/or pulmonary congestion, and intraventricular block predicted
      only late mortality (up to 5 years after myocardial infarction). Only age was an
      independent predictor of all-cause mortality more than 5 years after myocardial
      infarction. After adjusting for age at myocardial infarction and these clinical
      variables, preinfarction-measured risk factors such as 1-hour postload serum
      glucose (positively) and 1-second forced expiratory volume (inversely) were
      significantly associated with late mortality up to 5 years, whereas systolic
      blood pressure was the only independent predictor of late mortality after 5
      years. CONCLUSIONS: This study has confirmed the importance of age at myocardial
      infarction and clinical indicators of complications such as Killip class 3 or 4,
      radiological evidence of pulmonary congestion, and ventricular arrhythmias or
      intraventricular block as the prognostic determinants of myocardial infarction.
      In addition, some of the preinfarction-measured standard risk factors for CHD
      were found to predict long-term prognosis independent of age and clinical
      factors.

PMID- 8252670
TI  - Characterization of spatial patterns of flow within the reperfused myocardium by
      myocardial contrast echocardiography. Implications in determining extent of
      myocardial salvage.
AB  - BACKGROUND: Since myocardial blood flow changes dynamically after reperfusion and
      since both hyperemia and impairment in microvascular function exist within the
      acutely reperfused bed, we sought to investigate the role of myocardial contrast
      echocardiography (MCE) in (1) defining the temporal variability in perfusion
      patterns after reflow and relating these to microsphere-derived blood flow; (2)
      differentiating viable from infarcted tissue during different periods of reflow;
      and (3) defining spatial perfusion patterns within the infarct bed in response to
      exogenously induced maximal vasodilation and relating these to infarct size and
      extent of myocardial salvage. METHODS AND RESULTS: Twenty-one dogs with 3 hours
      of left anterior descending coronary artery occlusion and 2 to 3 hours of reflow
      were studied. MCE was performed at 15 and 45 minutes and 2 and 3 hours after
      reflow. It was also performed at either 2 or 3 hours after reflow in the presence
      of 0.56 mg/kg of dipyridamole. Radiolabeled microsphere-derived blood flow was
      measured at 15 minutes and 2 and 3 hours after reflow and during dipyridamole
      effect. Infarct size was measured at the end of the experiment by use of
      triphenyl tetrazolium chloride. MCE data were processed with color-coding schemes
      that highlighted differences in myocardial videointensities in proportion to the
      concentration of microbubbles within the microvasculature. There was significant
      variability in MCE-defined perfusion patterns after reflow, with contrast defects
      noted mainly within the endocardium. There were fair and significant (P < .05)
      correlation (r = -.73 to r = -.55) between MCE defect size and normalized
      endocardial blood flow. Except at 15 minutes after reflow, there was poor
      correlation (r = .31 to r = .51) between MCE defect and infarct sizes. Even at 15
      minutes after reflow, MCE defect size underestimated infarct size by 50%. In
      comparison, in the presence of dipyridamole, MCE defect size correlated strongly
      (r = .87, P < .001) with infarct size and reasonably well with normalized
      transmural blood flow (r = -.62, P = .04). Moreover, the topography of the MCE
      perfusion defect reflected the topography of the infarct. CONCLUSIONS: MCE
      revealed striking temporal heterogeneity in the spatial distribution of
      myocardial perfusion during postischemia reflow and either significantly
      underestimated or did not correlate with infarct size during reperfusion. Because
      of abnormalities in coronary vascular reserve specific to infarcted tissue, MCE
      in conjunction with intravenous dipyridamole depicted, in vivo, the actual
      topography of the infarct with remarkable accuracy.

PMID- 8252671
TI  - Radiofrequency catheter ablation of idiopathic left ventricular tachycardia
      guided by a Purkinje potential.
AB  - BACKGROUND: Verapamil-sensitive, idiopathic left ventricular tachycardia (ILVT)
      with right bundle branch block configuration and left-axis deviation has been
      suggested to originate from the left posterior fascicle. The purpose of this
      study was to determine how frequently potentials generated by the Purkinje fiber
      network (P potential) can be recorded preceding ventricular activation, and the
      role of the P potential in guiding radiofrequency catheter ablation. METHODS AND
      RESULTS: Eight patients (mean age, 26 +/- 10 years) with ILVT (cycle length, 346
      +/- 59 milliseconds) were studied. Right and left ventricular endocardial mapping
      during tachycardia identified earliest ventricular activation at the
      posteroapical left ventricular septum. In all patients, earliest ventricular
      activation during tachycardia was preceded by a distinct potential. This
      potential also preceded ventricular activation during sinus rhythm, consistent
      with activation of a segment of the left posterior fascicle (P potential). The
      earliest recorded P potential preceded the QRS during tachycardia by 15 to 42
      milliseconds (mean, 27 +/- 9 milliseconds). The application of radiofrequency
      current at 1 to 4 sites (median, 1) eliminated ILVT in all eight patients. In the
      seven patients with P potentials recorded at multiple sites within the
      posteroapical septum, ablation was successful at the site of the earliest P
      potential and unrelated to the timing of ventricular activation. In the remaining
      patient, ablation was successful at a site recording a late P potential fusing
      with earliest ventricular activation. During follow-up (1 to 67 months; median,
      10.5) ILVT recurred only in the latter patient. Pace mapping during tachycardia
      at the successful ablation site in four patients produced a similar QRS with
      stimulus-QRS interval equal to P-QRS interval during tachycardia. However, a
      similar QRS was obtained by pacing at nearby sites that recorded a later P
      potential. CONCLUSIONS: These findings support the hypothesis that ILVT
      originates from the Purkinje network of the left posterior fascicle. A P
      potential can be recorded at the posteroapical left ventricular septum during
      ILVT, and ablation is successful at the site recording the earliest P potential.
      Pace mapping with similar QRS is not specific due to capture of the Purkinje
      fiber network at a site remote from the origin of the tachycardia.

PMID- 8252672
TI  - Value of the P-wave signal-averaged ECG for predicting atrial fibrillation after
      cardiac surgery.
AB  - BACKGROUND: Atrial fibrillation (AF) is a commonly encountered arrhythmia in
      clinical practice, and it occurs frequently after cardiac surgery. The P-wave
      signal-averaged (SA) ECG noninvasively detects atrial conduction delay. Prior
      studies have described greater P-wave prolongation in patients with a history of
      AF, but prospective studies have not been performed. METHODS AND RESULTS:
      Consecutive patients undergoing cardiac surgery were enrolled. The P-wave SAECG
      was recorded before surgery from three orthogonal leads using a sinus P-wave
      template and a cross-correlation function. The averaged P wave was filtered with
      a least-squares-fit filter and combined into a vector magnitude, and total P-wave
      duration was measured. Patients were observed after cardiac surgery for the
      development of AF. One hundred thirty patients were enrolled, and 33 (25%)
      developed AF 2.6 +/- 2.0 days after surgery. Patients with AF more often had left
      ventricular hypertrophy on ECG (P < .05) and had a lower ejection fraction (P <
      .05). The P-wave duration on the SAECG was significantly longer in the AF
      patients than in those without AF: 152 +/- 18 versus 139 +/- 17 milliseconds (P <
      .001). An SAECG P-wave duration > 140 milliseconds predicted AF with sensitivity
      of 77%, specificity of 55%, positive predictive accuracy of 37%, and negative
      predictive accuracy of 87%. The likelihood of experiencing AF was increased 3.9
      fold if the SAECG P-wave duration was prolonged. P-wave SAECG results were
      independent of other clinical variables by multivariate analysis. CONCLUSIONS:
      The P-wave duration recorded with the SAECG is a potent, accurate, and
      independent predictor of AF after cardiac surgery.

PMID- 8252673
TI  - Ventricular fusion during resetting and entrainment of orthodromic
      supraventricular tachycardia involving septal accessory pathways. Implications
      for the differential diagnosis with atrioventricular nodal reentry.
AB  - BACKGROUND: Ventricular fusion during transient entrainment of orthodromic
      atrioventricular reciprocating tachycardias (OAVRT) was originally found to be
      absent and recently observed only with left ventricular stimulation. However,
      previous studies were restricted to cases with a left free wall accessory
      pathway. The hypothesis of the present study was that fusion is likely during
      resetting and entrainment of OAVRT with right ventricular stimulation if the
      accessory pathway is septally located, since its insertion is relatively close to
      the stimulation site. This phenomenon can help in the differential diagnosis with
      atrioventricular nodal reentry (AVNR). METHODS AND RESULTS: We performed
      programmed right ventricular stimulation during regular inducible
      supraventricular tachycardia with concentric atrial activation in 44 patients--20
      with OAVRT and 24 with AVNR. Fusion in the ECG morphology of extrastimuli
      producing resetting was observed in 19 of 19 OAVRT but in 0 of 11 AVNR reset (P <
      .001). Transient entrainment was demonstrated in all 31 cases undergoing rapid
      ventricular pacing (14 OAVRT and 17 AVNR). Entrainment with fusion occurred in 13
      of 14 OAVRT and in 0 of 17 AVNR (P < .001). Fusion was critically dependent on
      the coupling intervals or pacing rates, sometimes having a narrow window for its
      observation. CONCLUSIONS: The relative proximity (conduction time) among pacing
      site, site of entrance to a reentrant circuit, and site of exit from the circuit
      to the paced chamber are critical for the occurrence of fusion during resetting
      and/or entrainment. The presence or absence of fusion during these phenomena can
      help in the differential diagnosis of certain supraventricular tachycardias.

PMID- 8252674
TI  - Effects of adenosine on rate-dependent atrioventricular nodal function. Potential
      roles in tachycardia termination and physiological regulation.
AB  - BACKGROUND: Adenosine is well known to depress atrioventricular (AV) nodal
      conduction, but the potential interactions between adenosine and functional AV
      nodal properties have not been explored. The purpose of the present study was to
      determine (1) whether exogenous adenosine modifies the rate-dependent properties
      of the AV node, (2) to what extent such changes underlie the actions of adenosine
      in an in vitro model of AV reentrant tachycardia (AVRT), and (3) the potential
      role of endogenous adenosine in rate-induced AV nodal responses. METHODS AND
      RESULTS: The functional properties of AV nodal recovery (defining the conduction
      delay of a single premature activation), facilitation (effect of short cycles on
      subsequent nodal recovery), and fatigue (slowly developing AV nodal delay at a
      rapid rate) were studied selectively in isolated, superfused rabbit and guinea
      pig cardiac preparations. Exogenous adenosine increased AV nodal fatigue and
      attenuated facilitation, resulting in tachycardia-dependent increases in AH
      interval and AV nodal effective refractory period (AVERP). In experimental AVRT,
      adenosine caused greater increases in tachycardia cycle length (T) and AVERP as
      tachycardia rate increased. AVRT was sustained when AVERP/T was < 1, and
      adenosine suppressed AVRT by increasing the slope of the AVERP/T versus
      tachycardia rate relation, causing the critical ratio of 1 to be attained at
      slower rates. A mathematical model incorporating quantitative descriptors of
      recovery, facilitation, and fatigue accounted for changes in AH interval, AVERP,
      tachycardia cycle length, and AVERP/T under control conditions and in the
      presence of adenosine. In the absence of exogenous adenosine, 8
      phenyltheophylline (10 mumol/L), an adenosine receptor antagonist, did not alter
      recovery or facilitation but significantly reduced rate-related fatigue (by 31 +/
      8%, mean +/- SEM, P < .05, in rabbit hearts; 46 +/- 5%, P < .01, in guinea pig
      hearts). Combined inhibition of adenosine deaminase (with erythro-9-[2-hydroxy-3
      nonyl]-adenine hydrochloride, 5 mumol/L) and adenosine uptake (with dipyridamole,
      1 mumol/L) increased fatigue in the absence of exogenous adenosine by 57 +/- 20%
      (P < .05). CONCLUSIONS: We conclude that (1) exogenously administered adenosine
      increases AV nodal fatigue and reduces facilitation, without altering AV nodal
      recovery; (2) these changes cause rate-dependent AV nodal depression, which plays
      a role in adenosine's actions on experimental AVRT; and (3) endogenous adenosine
      receptor activation plays a role in physiological AV nodal fatigue. Adenosine's
      ability to terminate reentrant supraventricular tachycardia may be due, at least
      in part, to its ability to enhance the physiological conduction slowing that
      results from sustained increases in AV nodal activation rate.

PMID- 8252675
TI  - Optimization of biphasic waveforms for human nonthoracotomy defibrillation.
AB  - BACKGROUND: Biphasic waveforms reduce defibrillation threshold (DFT) in a wide
      variety of models. Although there are several human studies of long-duration,
      high-tilt biphasic waveform defibrillation, the specific biphasic waveform shape
      required to achieve optimal DFT reduction is unknown. METHODS AND RESULTS: This
      study tested the effect of single capacitor biphasic waveform tilt modification
      on DFT using a paired study design in 18 patients undergoing nonthoracotomy
      defibrillator implantation. Baseline DFT was obtained using a 65% tilt,
      simultaneous pulse, bidirectional monophasic shock from a right ventricular
      cathode to a coronary sinus or superior vena cava lead and a subscapular patch.
      The single-capacitor biphasic waveform shocks, delivered over the same pathways,
      consisted of either both phases at 65% tilt (65/65 biphasic waveform) to produce
      an overall tilt of 88% and a delivered energy 11% greater than monophasic shock
      or both phases at 42% tilt (42/42 biphasic waveform) to produce an overall tilt
      of 66% and delivered energy equal to monophasic shock. The 65/65 biphasic
      waveform reduced stored energy DFT 25%, from 16.2 +/- 4.4 J with monophasic shock
      to 12.1 +/- 5.3 J (P < .02); however, it did not significantly reduce the
      delivered energy DFT. In contrast, the 42/42 biphasic waveform required 49% less
      stored energy (16.2 +/- 4.4 J, monophasic shock, vs 8.3 +/- 3.3 J, biphasic
      waveform; P < .001) and 49% less delivered energy (14.2 +/- 3.8 J, monophasic
      shock, vs 7.3 +/- 2.9 J, biphasic waveform; P < .001) than monophasic shock for
      successful defibrillation. The 42/42 biphasic waveform delivered energy DFT was
      4.6 +/- 5.2 J (39%) less than 65/65 biphasic waveform DFT (P < .002).
      CONCLUSIONS: DFT reduction is an inherent electrophysiological property of
      biphasic waveforms that is independent of delivered energy. Overall biphasic
      waveform tilt and the relative amplitudes of the waveform phases are important
      factors in defibrillation efficacy. Defibrillation with a 42/42 biphasic waveform
      is more efficacious than 65/65 biphasic waveform defibrillation; however, the
      optimal biphasic waveform remains unknown.

PMID- 8252676
TI  - Low-energy endocardial defibrillation using an axillary or a pectoral thoracic
      electrode location.
AB  - BACKGROUND: A significant proportion of patients receiving endocardial
      defibrillation lead systems must accept either high defibrillation thresholds
      (DFTs) with lower safety margins or lead implantation by thoracotomy. We examined
      the feasibility of achieving universal application of endocardial leads and lower
      defibrillation energy requirements by optimizing the lead system location in
      conjunction with biphasic shocks. METHODS AND RESULTS: Two defibrillation
      catheter electrodes were positioned in the right ventricle and superior vena
      cava. Thoracic patch electrodes were placed at three sites (apical, pectoral, and
      axillary). Fifteen-joule, 10-J, and 5-J bidirectional simultaneous biphasic
      shocks were delivered across three different triple electrode configurations
      (right ventricle, superior vena cava, and patch) after inducing ventricular
      fibrillation (VF), and DFT was determined. All patients in whom VF was
      reproducibly inducible (14 patients) could be reproducibly defibrillated at 15 J
      at one or more patch electrode locations. Fifteen-joule shocks were effective at
      three thoracic electrode locations in 12 patients and at two electrode locations
      in 6 patients. The lowest mean single-shock DFT was 8.1 +/- 3.8 J. In 4 patients,
      ventricular flutter was reproducibly induced and reverted at 15 J in all
      patients. Mean DFT for the axillary location was 8.3 +/- 3.5 J and was
      significantly lower than apical (12.8 +/- 5.6 J, P = .008) and pectoral (11.6 +/-
      4.1 J, P < .04) patch locations. The probability of success was significantly
      higher at 10 J with axillary location (78% of patients, P < .03 compared with
      both other sites) and at 15 J (P < .05 compared with the apical location). Low
      energy endocardial defibrillation (< or = 10 J) was feasible in 10 of 14 tested
      patients at more than 1 thoracic electrode location at 10 J, whereas only 1 of 7
      successful patients could be reverted at more than 1 electrode location at 5 J (P
      < .02). CONCLUSIONS: The use of axillary or pectoral patch lead location can
      allow endocardial defibrillation with biphasic shocks at energies < or = 15 J in
      this lead configuration. Virtually universal application of endocardial
      defibrillation lead systems can be predicted from these data. Reduction in
      maximum pulse generator output to < or = 25 J using these two thoracic electrode
      locations with bidirectional shocks can be feasible and maintain an adequate
      safety margin and permit thoracic pulse generator implantation. Lowering
      endocardial defibrillation energy < 10 J requires increasing specificity of
      thoracic electrode location.

PMID- 8252677
TI  - Defibrillating shocks delivered to the heart impair efferent sympathetic
      responsiveness.
AB  - BACKGROUND: Functional studies indicate that sympathetic efferents are located in
      the superficial subepicardium and vagal efferents are located in the
      subendocardium. It is possible that electrical shocks applied directly to the
      heart might affect the function of these autonomic nerves. METHODS AND RESULTS:
      Low- (< or = 1 J), medium- (6 to 16 J), or high- (30 to 35 J) energy truncated
      monophasic exponential shocks, synchronized to the R wave during sinus rhythm,
      were delivered over implantable patches sutured inside the pericardium in
      anesthetized open-chest dogs. Shortening of ventricular effective refractory
      period (ERP), produced by bilateral ansae subclaviae stimulation (SS), was
      measured before and after shock delivery. High-energy shocks shifted the SS
      frequency-ERP response curves downward and to the right (P < .001) for sites
      beneath and apical to the patches; ERP shortening at basal sites remained
      unchanged. Such sympathetic attenuation occurred with shocks > 10 J but not with
      shocks < or = 10 J, was noted 15 minutes after the shock, and showed incomplete
      return to control values at 3 hours. Neither low- nor high-energy shocks affected
      norepinephrine dose-ERP response curves, indicating normal myocardial
      responsiveness. Low- and high-energy shocks did not attenuate bilateral cervical
      vagal stimulation-induced ERP prolongation. High-energy shocks delivered over
      patches sutured to the outside of the pericardium showed no effects on
      sympathetic response, suggesting a protective effect of the pericardium against
      shock-induced sympathetic attenuation. CONCLUSIONS: DC shocks > 10 J delivered
      directly to the epicardium attenuated efferent sympathetic neural function. Such
      changes may affect electrophysiological, as well as hemodynamic, responses to
      sympathetic neural stimulation after cardioversion-defibrillation.

PMID- 8252678
TI  - Body surface distribution of abnormally low QRST areas in patients with Wolff
      Parkinson-White syndrome. Evidence for continuation of repolarization
      abnormalities before and after catheter ablation.
AB  - BACKGROUND: Whether the Wolff-Parkinson-White syndrome (WPW) is associated with
      repolarization abnormalities is controversial. The QRST isointegral map (I-map)
      is theoretically independent of the activation sequence and dependent on
      repolarization properties. There have been no reports concerning the effects of
      radiofrequency (RF) catheter ablation of accessory pathway (AP) on repolarization
      properties analyzed by I-mapping. METHODS AND RESULTS: I-maps were constructed
      from data recorded in 38 patients with WPW to investigate repolarization
      properties and their body surface distribution in a physiological state, without
      pharmacological influences, and in 13 ablated patients to elucidate the effects
      of RF ablation on repolarization properties. Patients were divided into three
      groups: group A, 15 patients with type A WPW (left-sided AP); group B, 10
      patients with type B (right-sided AP); and group C, 13 patients who were
      successfully ablated. Group C consisted of three subgroups: subgroup CA, 7
      patients with type A WPW; subgroup CB, 3 patients with type B WPW; and subgroup
      CC, 3 patients with concealed WPW. Controls consisted of 608 normals. Although I
      maps of WPW were highly (r = .87) correlated with the mean normal I-map, the
      location of the minimum in groups A and B differed significantly from that in
      normals. The minimum was located over the upper right anterior chest in normal
      subjects, over the back in 82% of 22 patients with type A WPW including ablated
      patients (groups A+CA), and over the mid to lower right anterior chest in 62% of
      13 patients with type B WPW including ablated patients (groups B+CB). Groups A+CA
      and B+CB had an abnormally low QRST area ("-2SD area") over the back and right
      anterior chest, respectively. The abnormally located minimum and the "-2SD area"
      were present in 7 of 10 ablated patients with manifest WPW (groups CA+CB). After
      RF ablation, the distribution of the minimum, initially abnormal, became normal
      over a period of days or weeks, and the "-2SD area" disappeared over 1 week in
      all 7 patients. Correlation coefficients between I-maps and the mean normal I-map
      increased after RF ablation. CONCLUSIONS: (1) WPW is often associated with
      abnormalities in repolarization properties. (2) Repolarization abnormalities were
      located over the back in type A WPW and over the right mid to lower chest in type
      B WPW: (3) The abnormalities remain immediately after RF ablation and gradually
      normalize. These findings support the concept that ST-T abnormalities in 12-lead
      ECGs following RF ablation are attributable to "cardiac memory."

PMID- 8252679
TI  - Electrocardiographic abnormalities and 30-year mortality among white and black
      men of the Charleston Heart Study.
AB  - BACKGROUND: The long-term predictive significance of a single ECG tracing for
      mortality was explored among the white and black men of the Charleston Heart
      Study. METHODS AND RESULTS: The 1960 baseline tracings of men ages 35 to 74 in
      the Charleston Heart Study cohort were coded according to the Minnesota
      classification. Tracings were categorized as being normal or having minor or
      major abnormalities. The 30-year vital status was ascertained for the cohort, and
      the association between ECG findings and coronary and all-cause mortality was
      evaluated. The proportion of black men with major abnormalities at the 1960
      baseline examination was almost twice that of white men. Rates of all-cause
      mortality increased with severity of abnormalities for white and black men. The
      absolute excess risk for black men with major abnormalities was 23.3 per 1000
      person-years and 12.8 for white men. The excess risk for coronary mortality was
      7.3 for white men and 6.5 for black men. CONCLUSIONS: Many of the findings in
      this study confirm earlier associations derived from studies of white populations
      and extend the observations to black men. However, the magnitude of the relative
      risk for mortality was different for white and black men. After controlling for
      traditional coronary disease risk factors and minor abnormalities, white men with
      major abnormalities were 2.72 (95% confidence interval, 1.47, 5.04) times more
      likely to die of coronary disease compared with black men, who were 1.95 (95%
      confidence interval, 0.93, 4.11) times more likely to die of coronary disease.

PMID- 8252680
TI  - A new noninvasive method for the estimation of peak dP/dt.
AB  - BACKGROUND: Peak dP/dt is a good index of ventricular performance that is not
      influenced by afterload, wall motion abnormalities, or the variations in
      ventricular anatomy and morphology commonly encountered among patients with
      congenital heart disease. Unfortunately, the clinical utility of peak dP/dt has
      been limited by the fact that its measurement generally requires an
      intraventricular catheter. However, peak dP/dt occurs during isovolumetric
      contraction, and the pressure rise during isovolumetric contraction is almost
      linear. Therefore, the mean dP/dt during isovolumetric contraction (mean
      dP/dtic), ie, the ratio of the rise in pressure during isovolumetric contraction
      (aortic diastolic pressure minus the systemic ventricular end-diastolic pressure
      [VEDP]) over the isovolumetric contraction time, should provide a good estimate
      of peak dP/dt that could be generated noninvasively. METHODS AND RESULTS:
      Echo/phonocardiography was used to measure the isovolumetric contraction time and
      a blood pressure cuff to estimate aortic diastolic pressure of 27 patients (age,
      1 day to 77 years) with congenital or acquired heart disease. VEDP was determined
      by three methods: (1) intraventricular catheter, (2) assumed VEDP of 10 mm Hg,
      and (3) assignment of a normal or elevated value on the basis of clinical
      history. The three estimates of mean dP/dtic thus generated were compared with
      simultaneous measurements of peak dP/dt obtained during cardiac catheterization.
      Invasively measured peak dP/dt correlated well with the indirect determinations
      (r = .95, .89, and .92 for methods 1, 2, and 3, respectively; P < .0001).
      CONCLUSIONS: Echo/phonocardiography can be used in conjunction with a blood
      pressure cuff and indirect estimates of VEDP to generate mean dP/dtic, an index
      of ventricular function that approximates and closely correlates with peak dP/dt.
      This noninvasive measurement can be obtained in almost any patient and may be
      useful in the assessment of ventricular performance in a variety of
      cardiovascular disorders.

PMID- 8252681
TI  - Myocardial force-frequency defect in mitral regurgitation heart failure is
      reversed by forskolin.
AB  - BACKGROUND: Postoperative ejection phase parameters and patient survival rates
      for mitral valve replacement surgery are considerably lower than for similar
      aortic valve surgery. While chordal transection probably is the major contributor
      to the lowered values, there is also evidence for decreased preoperative
      myocardial contractile reserve in mitral regurgitation patients. This study
      characterizes abnormalities in the force-frequency relation that may underlie
      impaired function of myocardium isolated from mitral regurgitation patients with
      New York Heart Association class II-III heart failure. METHODS AND RESULTS: Left
      ventricular epicardial myocardium was obtained by surgical biopsy during mitral
      valve replacement surgery in patients with mitral regurgitation heart failure
      (left ventricular ejection fraction, 0.64 +/- 0.05) and during coronary artery
      bypass surgery in patients with normal ventricular function. The steady-state
      twitch tension versus frequency relation was measured in myocardial strip
      preparations (37 degree C, 12 to 228 min-1) in the absence and presence of
      forskolin. Relative to normal function, peak isometric twitch tension in mitral
      regurgitation is depressed by 50% (P < .02) and 74% (P < .003) at contraction
      frequencies of 60 min-1 and 168 min-1, respectively. The slope of the tension
      frequency curve is blunted and its peak is shifted to a lower frequency (mitral
      regurgitation: 134 min-1; normal function: 173 min-1; P < .02). The myosin heavy
      chain concentration did not differ between mitral regurgitation and normal
      function strips (53 +/- 4 versus 54 +/- 4 nmol/g blotted wt). Forskolin (0.5
      mumol/L) completely reversed the tension depression, blunting, and the lowered
      peak frequency in the mitral regurgitation preparations. CONCLUSIONS:
      Preoperatively, myocardial tension generation in mitral regurgitation patients is
      severely depressed, and the force-frequency curve is blunted and has a negative
      slope in the exercise range of heart rates. The reversal of these defects by
      forskolin suggests that abnormal excitation-contraction coupling may underlie the
      decreased contractile reserve in mitral regurgitation patients.

PMID- 8252682
TI  - Intraventricular early diastolic filling during acute myocardial ischemia,
      assessment by multigated color m-mode Doppler echocardiography.
AB  - BACKGROUND: Color M-mode Doppler echocardiography has been suggested as a new
      noninvasive technique for assessing left ventricular diastolic function. The
      present study investigated intraventricular filling pattern by color M-mode
      Doppler in patients during percutaneous transluminal coronary angioplasty (PTCA).
      In a dog model of myocardial ischemia, the color M-mode flow pattern was related
      to indices of global and regional myocardial function. METHODS AND RESULTS: From
      color M-mode images, the time difference (TD) between occurrence of peak velocity
      in the apical region and at the mitral tip was determined in 20 patients and
      eight anesthetized dogs during coronary occlusions. During PTCA, the timing of
      peak velocity was progressively delayed from mitral valve to apex. Consistent
      with this, the dog model showed delayed apical filling during coronary occlusion;
      TD increased from 18 +/- 4 to 71 +/- 9 milliseconds (P < .01). In the ischemic
      region, systolic shortening (sonomicrometry) decreased from 20 +/- 3% to -5 +/-
      2% (p < .01). The one-third filling fraction decreased from 59 +/- 5% to 31 +/-
      6% (P < .01) and correlated with TD (r = .85, P < .01). The time constant of
      isovolumic relaxation (tau) increased slightly and correlated with TD (r = .81, P
      < .01). Pacing tachycardia, caval constriction, and volume loading were performed
      to mimic the ischemia-induced changes in heart rate, stroke volume, and
      intracavitary filling pressure, respectively. There were no significant changes
      in TD or tau during these interventions. CONCLUSIONS: Color M-mode Doppler
      echocardiography showed a marked delay of apical peak filling velocity during
      PTCA. The experimental data suggest that this reflects retarded filling of the
      ischemic ventricle. Thus, color M-mode Doppler may provide a useful method for
      assessing diastolic dysfunction.

PMID- 8252683
TI  - Increased aortic impedance precedes peripheral vasoconstriction at the early
      stage of ventricular failure in the paced canine model.
AB  - BACKGROUND: Aortic input impedance is altered in patients with congestive heart
      failure. However, little is known about whether this vascular response is an
      early change or a late manifestation of left ventricular dysfunction. METHODS AND
      RESULTS: This investigation used a paced canine model of congestive heart failure
      to demonstrate that abnormal aortic input impedance does evolve in the setting of
      ventricular systolic dysfunction and to prospectively define the time course of
      change in aortic input impedance and conduit vessel compliance. Studies were
      performed in closed-chest conditioned beagles aged 1 to 2 years that underwent
      hemodynamic evaluation at baseline and after induction of left ventricular
      dysfunction by rapid ventricular pacing. Within 48 hours of the onset of rapid
      ventricular pacing, we observed mild left ventricular systolic dysfunction with
      an echocardiographically derived left ventricular ejection fraction of 37% (p <
      .001 compared with baseline) measured during interruption of rapid ventricular
      pacing. Concomitant with this reduction in left ventricular systolic function,
      the aortic input impedance spectrum was shifted above baseline in all dogs
      studied. Characteristic impedance of the aorta significantly increased from 121
      +/- 65 dynes.s/cm5 to 186 +/- 114 dynes.s/cm5 (P < .02), and a significant
      increase in the first modulus of impedance from 137 +/- 43 dynes.s/cm5 to 228 +/-
      139 dynes.s/cm5 was observed (P < .05). Although characteristic aortic impedance
      increased by 50%, there was at this point no change in peripheral vascular
      resistance. Therefore, these abnormalities in aortic input impedance are
      representative of an early vascular change that evolves in response to
      ventricular systolic dysfunction. CONCLUSIONS: Considering the early appearance
      of these findings, the resultant impaired power transfer and reduced conduit
      vessel compliance likely contribute to the progression of abnormal myocardial
      energetics and systolic dysfunction characteristic of ventricular failure.

PMID- 8252684
TI  - Doppler hemodynamic profiles of 82 clinically and echocardiographically normal
      tricuspid valve prostheses.
AB  - BACKGROUND: Normal Doppler hemodynamics for tricuspid prostheses have not been
      well characterized in a large group of patients. Therefore, we analyzed
      comprehensive Doppler echocardiographic examinations of 82 patients with
      tricuspid prostheses that were normal by clinical and two-dimensional
      echocardiographic examinations to establish the normal hemodynamics of various
      types and sizes of tricuspid prostheses. METHODS AND RESULTS: The earliest
      complete postoperative echocardiographic study from each patient was chosen for
      analysis. Doppler examinations were analyzed on an off-line station from tapes or
      Doppler strip charts. Early velocity, atrial velocity, end-diastolic velocity,
      pressure half-time, and mean gradient were obtained by digitizing tricuspid
      velocity curves. The incidence of "physiological" tricuspid prosthetic
      regurgitation was noted. Ten Doppler cycles were measured for each patient, and
      maximal, minimal, and average measurements were recorded. The mean values +/- SD
      of early velocity, atrial velocity, end-diastolic velocity, mean gradient, and
      pressure half-time and incidence of mild prosthetic regurgitation were reported
      for each type of prosthesis, as were highest Doppler measurements for each valve
      type. Average pressure half-time was significantly lower for St Jude than for
      heterograft prostheses (P = .04). There were no significant differences between
      the valve types for mean gradient, early velocity, or incidence of prosthetic
      regurgitation. Increasing prosthesis size was associated with lower average
      pressure half-time for heterograft prostheses (P = .024). Average differences
      (respiratory- and cycle-length-dependent) between maximal and minimal values for
      10 cardiac cycles were established for each prosthesis. CONCLUSIONS: This study
      establishes normal ranges for Doppler hemodynamics of various tricuspid
      prostheses and emphasizes the importance of measuring multiple cycles for each
      tricuspid prosthesis, regardless of cardiac rhythm.

PMID- 8252685
TI  - Platelet activation during coronary angioplasty in humans.
AB  - BACKGROUND: Previous studies have indicated that balloon angioplasty is
      associated with local platelet activation. In addition, different contrast media
      have different effects on thrombus formation during angioplasty in humans. We
      hypothesized that coronary angioplasty in humans is associated with activation of
      platelets to specific platelet agonists and that this activation may be
      differently modified by different angiographic contrast agents. METHODS AND
      RESULTS: We studied 25 patients referred for angioplasty of the left anterior
      descending or circumflex coronary arteries. All patients were pretreated with
      aspirin and received heparin. Blood samples for assessment of platelet
      aggregation to serotonin, ADP, epinephrine, and collagen were obtained from the
      coronary sinus before any contrast injection, after initial diagnostic contrast
      injections, and after three balloon inflations. Patients were randomized to
      receive iopamidol, diatrizoate, or ioxaglate. Contrast alone was not associated
      with altered platelet aggregation. However, balloon angioplasty was consistently
      associated with increased platelet aggregation to serotonin but not to ADP,
      epinephrine, or collagen. These effects were similar with the three contrast
      agents studied except that the use of iopamidol was associated with increased
      platelet responsiveness to all concentrations of ADP after balloon dilation.
      CONCLUSIONS: Coronary angioplasty in humans was associated with increased
      platelet aggregation in blood drawn from the coronary sinus. This effect was
      primarily seen when serotonin was used as an agonist.

PMID- 8252686
TI  - Coronary angioplasty. Statewide experience in California.
AB  - BACKGROUND: This report describes the in-hospital experience with percutaneous
      transluminal coronary angioplasty (PTCA) for the state of California in 1989.
      Data are derived from the statewide hospital discharge abstracts. METHODS AND
      RESULTS: A total of 24,883 PTCAs were performed; most patients (70%) were men and
      most procedures were single vessel (87%). About one fifth (19%) of patients had a
      principal diagnosis of acute myocardial infarction (AMI). Overall mortality was
      1.4% and was higher in the AMI group (4.2%) versus the non-AMI group (0.8%, P =
      .0001). Mortality was higher for AMI patients having PTCA on the day of or day
      after admission (5.5%) versus those treated later (2.6%, P = .0001). Five percent
      of patients had coronary artery bypass surgery (CABG) after PTCA; CABG was
      performed on the same day as PTCA in 61.7% of cases. Patients presenting with AMI
      were more likely to have CABG (7.1%) than non-AMI patients (4.5%, P = .0001).
      Mortality associated with CABG was 7.3% and was higher in the AMI group (12.0%)
      than in the non-AMI group (5.5%, P = .0001). Factors predictive of increased
      mortality by bivariate analysis included age > 63 years (2.1% mortality versus
      0.8% < or = 63, P = .01), female sex (1.9% versus 1.2% for men, P < .01), and the
      presence of diabetes (1.9% versus 1.3% for nondiabetics, P < .05). Multiple
      logistic regression showed that timings of PTCA with respect to admission (P =
      .004) and age (P = .05) were predictors of mortality, but female sex was
      predictive only in the non-AMI group (P = .03). Mean hospital charges were
      $19,597 (+/- SD, $18,213). Forty-two percent of the 110 hospitals performed more
      than the recommended minimum of 200 cases per year. The requirement for CABG
      during the same admission or the combined adverse outcome of CABG and/or death
      was increased in the lower-volume centers for both AMI and non-AMI patients (P <
      .001), although mortality alone was not. CONCLUSIONS: The mortality and need for
      CABG surgery in the statewide California PTCA experience is higher than that
      generally reported in the literature. In patients with an admitting diagnosis of
      AMI, the overall mortality was higher, as was the need for CABG and the
      associated CABG mortality. Most hospitals performed fewer than 200 PTCAs per
      year. Rates of CABG surgery and the combination of CABG and/or mortality,
      adjusted only for the presence or absence of AMI, were increased at the low
      volume institutions.

PMID- 8252687
TI  - Effects of intensive lipid-lowering therapy on the coronary arteries of
      asymptomatic subjects with elevated apolipoprotein B.
AB  - BACKGROUND: Do the benefits of intensive lipid-lowering therapy seen in
      symptomatic patients extend to high-risk subjects who have never had symptoms?
      METHODS AND RESULTS: Of 120 men completing the FATS trial, 91 were symptomatic
      and 29 asymptomatic. All had apolipoprotein B > or = 125 mg/dL, a positive family
      history, and coronary atherosclerosis. All were counseled in diet and randomized
      to intensive therapy: colestipol 10 g TID plus either niacin 1 g QID or
      lovastatin 20 mg BID or to conventional therapy: placebos, or colestipol if low
      density lipoprotein cholesterol was elevated. End points included quantitative
      arteriographic disease change and clinical events over a 2.5-year interval. At
      baseline, symptomatic and asymptomatic patients had comparable risk profiles, but
      proximal stenosis severity averaged 36% for symptomatic and 23% for asymptomatic
      patients (P < .001). Among the 91 symptomatic patients, those in the intensive
      group experienced definite (> or = 10%S) proximal lesion progression less
      frequently than conventional (24% of intensive versus 48% of conventional) and
      definite regression more frequently (36% of intensive versus 15% of conventional)
      (P = .009). Similarly, among the 29 asymptomatic patients, 19% of intensive
      versus 38% of conventional had progression and 31% of intensive versus 0% of
      conventional, regression (P = .04). Ischemia on baseline exercise tolerance
      testing was associated with significantly greater proximal disease progression
      among the asymptomatic patients. Clinical cardiovascular events (death,
      infarction, or revascularization) occurred in 10 of 38 symptomatic patients
      originally assigned to conventional therapy, compared with 5 of 76 symptomatic
      patients assigned to intensive (P < .01); no asymptomatic patient had an event.
      CONCLUSIONS: Asymptomatic subjects with this high-risk profile have less coronary
      disease at baseline than comparable symptomatic patients, and they have an
      excellent short-term clinical prognosis. However, asymptomatic subjects are
      indistinguishable from symptomatic patients in terms of their arterial disease
      progression with conventional therapy and their regression with intensive. These
      findings may justify an active treatment strategy in such subjects, particularly
      those with provokable ischemia.

PMID- 8252688
TI  - Responsiveness to bradykinin in veins of hypercholesterolemic humans.
AB  - BACKGROUND: Hypercholesterolemia impairs endothelium-dependent dilation in
      arteries. We tested the hypothesis that hypercholesterolemia impairs endothelium
      dependent vasodilation by an interaction between elevated plasma lipoproteins and
      a presumably normal endothelium using human veins in vivo; veins do not generally
      develop atherosclerosis and are appropriate for testing functional alterations.
      METHODS AND RESULTS: Full dose-response curves were constructed in 13
      hypercholesterolemic and 12 normocholesterolemic subjects by infusing bradykinin
      (0.25 to 508 ng/min) into hand veins preconstricted with the alpha-adrenergic
      agonist phenylephrine. The maximal relaxation induced by bradykinin was 80 +/-
      38% in the controls and 103 +/- 40% in subjects with hypercholesterolemia (P =
      .08). Responsiveness to bradykinin was also determined after infusion of
      indomethacin (5.4 micrograms/min), a cyclooxygenase inhibitor, to block the
      contribution of prostaglandins; maximal responsiveness was greater in
      hypercholesterolemic subjects (112 +/- 41%) than in controls (81 +/- 31%) (P =
      .03). Hypercholesterolemic subjects were more sensitive to bradykinin, with an
      ED50 of 4.2 ng/min versus 10.9 ng/min in controls (P = .05); a similarly
      increased sensitivity was found in the presence of indomethacin. The response to
      a maximally effective dose of nitroglycerin was greater in hypercholesterolemic
      subjects (142 +/- 31%) versus 106 +/- 28% in controls (P = .007). In five
      hypercholesterolemic subjects, treated with lovastatin to normalize serum
      cholesterol concentrations, maximal responsiveness to bradykinin decreased from
      103 +/- 52% to 80 +/- 28%. CONCLUSIONS: These results demonstrate that
      hypercholesterolemia in humans does not impair endothelium-derived relaxing
      factor-mediated venodilation.

PMID- 8252689
TI  - Plasma lipoproteins and progression of coronary artery disease evaluated by
      angiography and clinical events.
AB  - BACKGROUND: There is considerable evidence that remnants of triglyceride-rich
      lipoproteins may be particularly atherogenic. METHODS AND RESULTS: Levels of
      lipoprotein lipids and of apolipoprotein B in low-density lipoproteins were
      measured in 335 men and women enrolled in a study in which quantitative coronary
      angiography was carried out at 2-year intervals. Clinical events related to
      coronary disease occurred in 129 patients during the trial and in the subsequent
      follow-up period of 4 to 6 years. In multivariate analysis controlled for a
      number of nonlipid risk factors, high-density lipoprotein cholesterol was
      inversely related to the mean percentage increase in coronary artery stenosis in
      both men and women. Neither plasma triglycerides nor low-density lipoprotein
      cholesterol, triglycerides, or apolipoprotein B was related to change in
      stenosis, but a measure of remnants of triglyceride-rich lipoproteins, which
      included cholesterol in intermediate-density lipoproteins, was directly related
      to lesion progression. The same relations for these measures of plasma
      lipoprotein concentrations were found to hold for clinical events related to
      coronary artery atherosclerosis. CONCLUSIONS: In patients with established
      coronary heart disease, increased levels of remnants of triglyceride-rich
      lipoproteins and decreased levels of high-density lipoproteins appear to promote
      progression of coronary artery atherosclerosis, which in turn may lead to an
      untoward clinical event. No such relation could be shown for the level of
      components of low-density lipoproteins. These and other observations call for
      reevaluation of relations between particular species of lipoproteins containing
      apolipoprotein B and the pathogenesis of coronary artery atherosclerosis and
      coronary heart disease.

PMID- 8252690
TI  - Differences in coronary mortality can be explained by differences in cholesterol
      and saturated fat intakes in 40 countries but not in France and Finland. A
      paradox.
AB  - BACKGROUND: For decades, the coronary heart disease (CHD) mortality rate has been
      four or more times higher in Finland than in France despite comparable intakes of
      dietary cholesterol and saturated fat. A potential answer to this paradox is
      provided by this study of 40 countries and the analyses of other nutrients in the
      diets besides cholesterol and saturated fat. METHODS AND RESULTS: CHD death rates
      for men aged 55 to 64 years were derived from the World Health Organization
      annual vital statistics. Dietary intakes were gathered from the Food and
      Agriculture Organization of the United Nations database. Forty countries at
      various levels of economic development and 40 dietary variables were
      investigated, including a lipid score that combined the intakes of cholesterol
      and saturated fat (Cholesterol-Saturated Fat Index [CSI]). The CSI was
      significantly and positively related to CHD mortality in the 40 countries. The
      countries with low CSIs had low CHD death rates. Countries with high CSIs had a
      wide range of CHD death rates. France, Finland, and other Western industrialized
      countries had similar CSIs. After adjusting for cholesterol and saturated fat,
      milk and many components of milk (butterfat, milk protein, calcium from milk, and
      riboflavin) and total calcium remained positively related to CHD mortality for
      all 40 countries. There were differences in the consumption of these foods and
      nutrients in France and Finland. Milk and butterfat (fat from milk, cream,
      cheese, and butter) consumption was higher in Finland than in France. The
      consumption of plant foods, recently shown to be protective against CHD
      (vegetables and vegetable oils containing monounsaturated and polyunsaturated
      fatty acids), was greater in France than in Finland. CONCLUSIONS: Over the years,
      France and Finland, with similar intakes of cholesterol and saturated fat,
      consistently have had very different CHD mortality rates. This paradox may be
      explained as follows. Given a high intake of cholesterol and saturated fat, the
      country in which people also consume more plant foods, including small amounts of
      liquid vegetable oils, and more vegetables (more antioxidants) had lower rates of
      CHD mortality. On the other hand, milk and butterfat were associated with
      increased CHD mortality, possibly through their effects on thrombosis as well as
      on atherosclerosis.

PMID- 8252691
TI  - Effect of combined supplementation with alpha-tocopherol, ascorbate, and beta
      carotene on low-density lipoprotein oxidation.
AB  - BACKGROUND: Data continue to accumulate supporting a proatherogenic role for
      oxidized low-density lipoprotein (Ox-LDL). Antioxidant micronutrients such as
      ascorbate, alpha-tocopherol, and beta carotene, levels of which can be favorably
      manipulated by dietary measures without side effects, could be a safe approach in
      inhibiting LDL oxidation. In fact, in vitro studies have shown that all three
      antioxidants can inhibit LDL oxidation. The present study was undertaken to
      ascertain both the safety and antioxidant effect of combined supplementation with
      alpha-tocopherol, ascorbate, and beta carotene on LDL oxidation. METHODS AND
      RESULTS: The effect of combined supplementation with alpha-tocopherol (800 IU/d)
      plus ascorbate (1.0 g/d) and beta carotene (30 mg/d) on copper-catalyzed LDL
      oxidation was tested in a randomized, placebo-controlled study in two groups of
      12 male subjects over a 3-month period. Blood samples for the lipoprotein
      profile, antioxidant levels, and LDL isolation were obtained at baseline and at 3
      months. Neither placebo nor combined antioxidant therapy resulted in any side
      effects or exerted an adverse effect on the plasma lipoprotein profile. Compared
      with placebo, combined antioxidant therapy resulted in a significant increase in
      plasma ascorbate and lipid standardized alpha-tocopherol and beta carotene levels
      (2.6-, 4.1-, and 16.3-fold, respectively). At baseline, there were no significant
      differences in the time course curves and kinetics of LDL oxidation as evidenced
      by the thiobarbituric acid reacting substances (TBARS) assay and the formation of
      conjugated dienes. However, at 3 months, combined supplementation resulted in a
      twofold prolongation of the lag phase and a 40% decrease in the oxidation rate.
      The combined antioxidant group was also compared with a group that received 800
      IU of alpha-tocopherol only. Although the combined antioxidant group had
      significantly higher ascorbate and beta carotene levels than the group
      supplemented with alpha-tocopherol alone, there were no significant differences
      between the two groups with respect to LDL oxidation kinetics. CONCLUSIONS:
      Combined supplementation with ascorbate, beta carotene, and alpha-tocopherol is
      not superior to high-dose alpha-tocopherol alone in inhibiting LDL oxidation.
      Hence, alpha-tocopherol therapy should be favored in future coronary prevention
      trials involving antioxidants.

PMID- 8252692
TI  - Alcohol consumption and ultrasonographically assessed carotid artery wall
      thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC)
      Study Investigators.
AB  - BACKGROUND: Although much has been written in recent years about the relation
      between alcohol and atherosclerotic disease, controversy exists as to whether and
      how alcohol exerts an effect on atherosclerosis in different sites. METHODS AND
      RESULTS: We tested the hypothesis that alcohol consumption is associated
      inversely with carotid atherosclerosis in a population sample of 45- to 64-year
      old men and women who participated in the Atherosclerosis Risk in Communities
      (ARIC) Study and were free of cardiovascular disease at a baseline examination in
      1987 to 1989. B-mode ultrasonography was used to determine carotid artery intimal
      medial wall thickness and distensibility as indices of the degree of
      atherosclerosis. The level of alcohol consumption in the ARIC sample was
      generally low. Age-adjusted mean values of alcohol consumed (grams per week) were
      72.0 for white and 74.3 for nonwhite men and 24.8 for white and 11.2 for nonwhite
      women. After adjustments for age, artery depth, education, body mass index, sport
      index, cigarette-years of smoking, low-density lipoprotein cholesterol, and
      diabetes mellitus, there was no significant cross-sectional association of
      reported current alcohol intake with either carotid artery wall thickness (among
      white and nonwhite men and nonwhite women) or distensibility (in any of the four
      sex-race groups). Among white women, the adjusted mean value of carotid artery
      wall thickness tended to be higher in light to moderate drinkers than in never or
      rare drinkers, but the difference across drinking status categories was of
      borderline statistical significance (P = .04) and may be of little biological
      importance. CONCLUSIONS: The ARIC Study found no material cross-sectional
      association between current alcohol intake and carotid atherosclerosis but
      provides an opportunity in the future to study atherosclerosis progression and
      incident events in relation to alcohol consumption in a large population sample
      of men and women.

PMID- 8252693
TI  - Menopausal status influences ambulatory blood pressure levels and blood pressure
      changes during mental stress.
AB  - BACKGROUND: Frequent and large cardiovascular and neuroendocrine responses to
      psychological stress are thought to enhance an individual's risk for
      cardiovascular diseases. Preliminary data suggest that levels of reproductive
      hormones affect the magnitude of stress responses, perhaps contributing to the
      protective effect of ovarian hormones on premenopausal women's rates of coronary
      heart disease. METHODS AND RESULTS: Healthy middle-aged men and premenopausal and
      postmenopausal women performed a series of standardized mental and physical
      challenges while blood pressure, heart rate, plasma catecholamines, lipids, and
      lipoproteins were measured. Subjects then wore an ambulatory blood pressure
      monitor during two consecutive workdays. Results showed that postmenopausal women
      had larger mean +/- SEM stress-induced increases in systolic blood pressure (24.7
      +/- 2.2 mm Hg) and diastolic blood pressure (14.3 +/- 1.0 mm Hg) compared with
      either premenopausal women (16.9 +/- 1.3 and 10.2 +/- 0.9 mm Hg) or men (17.7 +/-
      1.5 and 10.9 +/- 1.1 mm Hg, respectively). Postmenopausal women and men had
      higher mean +/- SEM ambulatory diastolic blood pressure levels (75.5 +/- 3.2 and
      76.4 +/- 1.8 mm Hg) than did premenopausal women (69.9 +/- 2.2 mm Hg). Large
      blood pressure responses during public speaking were associated with high
      cholesterol levels and low educational attainment. CONCLUSIONS: Menopause is
      associated with enhanced stress-induced cardiovascular responses and elevated
      ambulatory blood pressure during the workday. These effects may contribute to the
      risk of cardiovascular morbidity and mortality after the menopause.

PMID- 8252694
TI  - Effects of different training intensities on 24-hour blood pressure in
      hypertensive subjects.
AB  - BACKGROUND: It is generally accepted that physical training decreases blood
      pressure in hypertensive subjects, but the importance of training intensity has
      not been established. This study compared the effects of endurance training at
      different intensities on ambulatory blood pressure and on blood pressure load
      (percentage of readings above 140/90 and 120/80 mm Hg during the waking and
      sleeping periods, respectively). METHODS AND RESULTS: Previously sedentary
      subjects with mild to moderate hypertension were evaluated in a crossover fashion
      according to a Latin square after a sedentary control period and after training
      at low and at moderate intensity corresponding to 50% and 70% of maximal oxygen
      uptake, respectively. Each period lasted 10 weeks. After training at moderate
      intensity, a higher maximal oxygen uptake was found compared with sedentary
      values but not after training at low intensity. Both training intensities exerted
      a similar antihypertensive effect of about 5 mm Hg for systolic and diastolic 24
      hour blood pressures. However, training at low intensity reduced blood pressure
      exclusively during the walking hours, whereas training at a moderate intensity
      reduced blood pressure only during the evening and sleeping hours. Waking blood
      pressure load decreased from 66% to 49% after training at low intensity, whereas
      sleeping blood pressure load decreased from 61% to 34% after training at moderate
      intensity (both P < .05). CONCLUSIONS: Low- and moderate-intensity training
      produce similar 24-hour blood pressure reductions, but each training intensity
      may interfere with different pathogenic effects associated with different blood
      pressure profiles.

PMID- 8252695
TI  - Soluble complement receptor type 1 inhibits the complement pathway and prevents
      contractile failure in the postischemic heart. Evidence that complement
      activation is required for neutrophil-mediated reperfusion injury.
AB  - BACKGROUND: Complement-mediated neutrophil activation has been hypothesized to be
      an important mechanism of reperfusion injury. It has been proposed that soluble
      complement receptor 1 (sCR1), a potent inhibitor of both classical and
      alternative complement pathways, may prevent the complement-dependent activation
      of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium
      and thereby inhibit PMN-derived free radical generation and prevent postischemic
      contractile failure. Therefore, we performed studies to determine the effects of
      sCR1 on contractile function, PMN adhesion, complement deposition, and PMN
      derived free radical generation in the postischemic heart. METHODS AND RESULTS:
      Studies were performed in an isolated rat heart model in which the isolated
      effects of given cellular or humoral factors could be determined. Plasma and PMNs
      were present to study the effects of sCR1 on contractile function, coronary flow,
      leukocyte adhesion, complement deposition, and PMN-derived free radical
      generation. Isolated rat hearts were perfused by the method of Langendorff (n =
      10 in each group) and subjected to 20 minutes of global ischemia and reperfusion
      with PMNs and plasma in the presence or absence of sCR1. Left ventricular
      developed pressure (LVDP), coronary flow (CF), left ventricular end-diastolic
      pressure (LVEDP), and rate-pressure product (RPP) were measured during the
      preischemic period, during 1-minute control infusion of PMNs and plasma, and on
      reflow following 20 minutes of global ischemia. During the preischemic control
      infusion, no significant alterations in the physiologic parameters were observed,
      and there was no measurable free radical generation. Reperfusion with sCR1
      markedly improved the recovery of postischemic contractile function. LVDP after
      45 minutes of reperfusion was 76 +/- 9.8% compared with 32 +/- 6.2% (P < .001).
      In addition, significant improvements in LVEDP, RPP, and CF were observed in
      hearts treated with sCR1. Additional experiments were also performed to determine
      the effect of sCR1 on complement-mediated PMN activation. Measurements of PMN
      derived free radical generation were performed in both isolated PMNs and the
      coronary effluent of hearts using electron paramagnetic resonance spectroscopy
      (EPR) with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). EPR
      measurements in both isolated PMNs and coronary effluent demonstrated that sCR1
      blocked complement-mediated free radical generation from the PMNs. Increased
      accumulation of PMNs was observed both in hearts treated with sCR1 and in those
      not treated with sCR1. Immunohistochemical staining of the postischemic
      myocardial tissue demonstrated marked complement deposition on the endothelial
      surface of small arterioles and capillaries, which was prevented by sCR1
      treatment. Thus, sCR1 did not prevent PMN adhesion but did prevent complement
      deposition with activation of the PMN oxidative burst. CONCLUSIONS: The potent
      complement inhibitor sCR1 was found to be effective at preventing postischemic
      myocardial contractile dysfunction and enhancing the recovery of coronary flow.
      This study demonstrated that complement activation occurs in postischemic
      myocardium and is necessary for activation of the neutrophil oxidative burst with
      the generation of reactive oxygen free radicals. The process of neutrophil
      adhesion, however, was not affected by sCR1 and was independent of complement
      factors. These findings demonstrate the sCR1 is a highly potent agent at
      preventing complement-mediated PMN activation and secondary free radical
      generation in the postischemic heart. This genetically engineered protein appears
      to be a promising therapeutic agent in the prevention of myocardial reperfusion
      injury.

PMID- 8252696
TI  - Ischemic preconditioning is associated with a delay in ischemia-induced reduction
      of beta-adrenergic signal transduction in rabbit hearts.
AB  - BACKGROUND: It has been reported that the A1-adenosine receptor mediates the
      cardioprotective effect of ischemic preconditioning. This receptor couples
      inhibitory guanine nucleotide-binding protein (Gi) and inhibits adenylate cyclase
      activity. However, the role of adenylate cyclase in preconditioning is unknown.
      METHODS AND RESULTS: We compared the effects of ischemia on the sarcolemmal beta
      adrenergic receptor density (Bmax), the stimulatory guanine nucleotide-binding
      protein (Gs) activity as determined by reconstitution with S49 lymphoma cyc-
      membranes, and baseline and maximally stimulated adenylate cyclase activities
      (ACAs) in control and preconditioned rabbit hearts. The control population (n =
      28) received 0, 10, 20, and 60 minutes of coronary occlusion (n = 6 to 8 per
      stage), and preconditioned rabbits (n = 24) received two cycles of alternating 5
      minute occlusion and reperfusion before sustained ischemia (n = 6 per stage). In
      control hearts, occlusion induced rapid and progressive reductions in the Bmax,
      Gs, and ACAs after 10 to 60 minutes of ischemia. Preconditioning did not affect
      the reduction in Bmax, but it preserved reductions in Gs activity and ACAs after
      10 to 20 but not 60 minutes of sustained ischemia. In another study, 18 rabbits
      were treated with pertussis toxin 48 hours before surgery to block Gi. During
      treatment, no significant difference was observed in the ischemia-induced
      reduction in ACAs in the ischemic region between control (n = 8) and
      preconditioned (n = 10) animals after 20 minutes of ischemia. CONCLUSIONS:
      Preconditioning delays ischemia-induced reductions in beta-adrenergic signal
      transduction. Inhibition of ACA is not the target effect of the A1-adenosine
      receptor-Gi pathway responsible for the cardioprotective role of preconditioning.

PMID- 8252697
TI  - Efficient and selective adenovirus-mediated gene transfer into vascular
      neointima.
AB  - BACKGROUND: Previous attempts to target arterial smooth muscle cells (SMCs) for
      gene delivery using liposomal or retroviral methods were limited by low
      transfection efficiency. We therefore evaluated the efficiency of adenovirus
      mediated gene delivery in cultured vascular SMCs and in an in vivo model of
      balloon injury-induced SMC cell proliferation. METHODS AND RESULTS: We used a
      recombinant adenovirus, Ad.RSV beta gal, which contained the beta-galactosidase
      (beta-gal) histochemical marker gene. For in vitro studies, rat aortic SMCs were
      incubated in media containing Ad.RSV beta gal for 5 to 120 minutes. The
      proportion of SMCs expressing the beta-gal gene product increased from 25% (5
      minute exposure) to 80% (120-minute exposure). For in vivo studies, uninjured and
      injured rat carotid segments were incubated with 0.5 to 1.0 x 10(9) pfu Ad.RSV
      beta gal for 45 minutes. Uninjured arteries showed adenovirus-mediated gene
      transfer limited to the endothelium. Injured arteries were exposed to adenovirus
      0, 3, 7, or 12 days after injury. In these segments, beta-gal expression was
      minimal with infection at 0 or 3 days after injury but marked when infection was
      delayed until 7 or 12 days after injury. Neointimal cells constituted the
      dominant target of adenovirus gene transfer, with efficiency of gene transfer
      ranging from 10% to > 75%. Medial SMCs, whether covered or uncovered by
      neointimal cells, were minimally infected. Infection with a control adenovirus
      vector showed no beta-gal staining. CONCLUSIONS: Recombinant adenovirus
      selectively targets neointimal cells with high-efficiency gene transfer. This
      suggests that adenovirus vectors should be useful in targeting cells for the
      delivery of genes whose products may be relevant to the treatment of restenosis.

PMID- 8252698
TI  - Identification of functional angiotensin II receptors on rat cardiac fibroblasts.
AB  - BACKGROUND: Cardiac hypertrophy results in an increased deposition of the
      extracellular matrix (ECM) proteins fibronectin and collagen. Recent evidence
      indicates that angiotensin II (Ang II) might have an important role in the
      development of myocardial fibrosis accompanying cardiac hypertrophy. We sought to
      determine whether fibroblasts of cardiac origin (isolated from neonatal and adult
      animals) express receptors for Ang II and to examine the ability of this peptide
      to regulate fibronectin and collagen gene expression in a cultured adult cardiac
      fibroblast cell preparation. METHODS AND RESULTS: Binding of 125I-Ang II to both
      neonatal and adult cardiac fibroblasts in culture was specific, reversible, and
      saturable, with the receptor evenly distributed over the cell population.
      Competition binding experiments with receptor-specific antagonists indicate that
      Ang II receptors found on both fibroblast types were of the AT1 subtype. Analysis
      of mRNA levels for the AT1 receptor indicates that adult cardiac fibroblasts
      express higher levels of the message than neonatal fibroblasts or cardiac
      myocytes. Addition of 10(-9) mol/L Ang II to adult cardiac fibroblasts resulted
      in an induction of ECM proteins above control levels, as determined through
      Northern blots and total collagen assays. CONCLUSIONS: Results from this study
      indicate that neonatal and adult rat cardiac fibroblasts in culture express AT1
      receptors for Ang II. Ang II stimulation of AT1 receptors results in an increased
      gene expression for ECM proteins. These data suggest that Ang II might have
      important regulatory roles over cardiac fibroblast function under normal and
      pathological conditions.

PMID- 8252699
TI  - Inhibition of endothelium-derived relaxing factor enhances myocardial stunning in
      conscious dogs.
AB  - BACKGROUND: Impaired endothelial-dependent vascular responses after coronary
      artery occlusion (CAO) and reperfusion (CAR) have been investigated extensively.
      However, it is not known whether impaired endogenous endothelium-derived relaxing
      factor production affects postischemic myocardial dysfunction, ie, myocardial
      stunning. METHODS AND RESULTS: Eight dogs were instrumented with an intracoronary
      catheter and an hydraulic occluder on the left circumflex coronary artery. The
      effects of a 10-minute CAO randomized with and without intracoronary
      administration of NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis
      inhibitor, were compared in the same conscious dogs. Postischemic regional
      contractile dysfunction in subendocardial and subepicardial as well as transmural
      wall thickening was measured with ultrasonic dimension crystals, and myocardial
      blood flow was measured with radioactive microspheres. Intracoronary infusion of
      L-NA did not affect systemic hemodynamics, and transmural myocardial blood flow
      was reduced slightly (-8%), but significantly, only in the left circumflex
      territory. The recovery of wall thickening was significantly delayed in the
      presence of L-NA compared with the absence of L-NA, eg, at 30-minute CAR, not
      only in the subendocardium (-76 +/- 9% versus -49 +/- 9%) but also in the
      subepicardium (-52 +/- 8% versus -29 +/- 7%). During CAO, blood flow was
      decreased identically in both conditions, and during CAR, the differences in
      blood flow were minor (7%). CONCLUSIONS: Inhibition of NO synthesis enhanced
      myocardial stunning transmurally in conscious dogs, potentially independent of
      its effects on blood flow.

PMID- 8252700
TI  - Limitation of infarct expansion and ventricular remodeling by late reperfusion.
      Study of time course and mechanism in a rat model.
AB  - BACKGROUND: Reperfusion of acutely infarcted myocardium may be beneficial in
      limiting infarct expansion and ventricular remodeling even if established after
      the time that salvage of ischemic myocardium is possible. METHODS AND RESULTS: To
      examine the permanency, time course, and mechanism of this effect of late
      reperfusion, 200 rats were randomized into one of four groups: (1) infarction
      with reperfusion after 1 to 2 hours, (2) infarction with reperfusion after 6 to 8
      hours, (3) infarction without reperfusion, and (4) sham operation. Surviving rats
      were killed at either 7 days, when infarct expansion has plateaued, or 21 days,
      when infarct healing is complete. In both 7- and 21-day analyses, late
      reperfusion did not reduce infarct size or degree of transmural necrosis but
      significantly limited infarct expansion, as measured by an index based on infarct
      endocardial segment lengthening and infarct wall thinning (expansion index at 7
      days: no reperfusion, 2.73 +/- 0.25, n = 13; reperfusion after 1 to 2 hours, 1.56
      +/- 0.13, n = 23, P < .001; reperfusion after 6 to 8 hours, 1.78 +/- 0.15, n =
      16, P = .002; at 21 days: no reperfusion, 3.45 +/- 0.39, n = 13; reperfusion
      after 1 to 2 hours, 2.21 +/- 0.24, n = 15, P = .01; reperfusion after 6 to 8
      hours, 2.02 +/- 0.20, n = 9, P = .01). Reperfusion after 6 to 8 hours was equally
      effective in limiting expansion as reperfusion after 1 to 2 hours. Late
      reperfusion also significantly reduced ventricular remodeling at 21 days, as
      measured by an index based on left ventricular cavity dilatation and noninfarcted
      myocardial hypertrophy (remodeling index at 21 days: no reperfusion, 2.67 +/-
      0.15, n = 13; reperfusion after 1 to 2 hours, 2.20 +/- 0.15, n = 15, P = .035;
      reperfusion after 6 to 8 hours, 2.12 +/- 0.10, n = 9, P = .012). Histological
      examination revealed that reperfusion accelerated the clearance of residual dead
      myofibrils, suggesting an increase in the rate of healing, and increased the
      degree of myocytolysis but did not change the final degree of infarct healing,
      tissue density, or viable subepicardial cells. CONCLUSIONS: Late reperfusion
      causes a permanent reduction in postinfarction expansion that is present even
      after complete infarct healing. The time after coronary occlusion in which
      reperfusion is of benefit in reducing subsequent expansion and remodeling is
      substantially longer than previously established. The mechanism by which late
      reperfusion limits expansion may involve changing the rate of healing and the
      nature of myocardial necrosis but does not involve preserving subepicardial
      cells.

PMID- 8252701
TI  - Selective pulmonary vasodilation by inhaled nitric oxide is due to hemoglobin
      inactivation.
AB  - BACKGROUND: Inhaled nitric oxide gas selectively decreases pulmonary artery
      pressure without affecting systemic arterial pressure. To determine if the
      selective pulmonary vasodilating effect of inhaled nitric oxide gas is due to
      inactivation by hemoglobin, we studied the ability of whole blood to inhibit the
      vasodilator activity of effluent from isolated lungs exposed to inhaled nitric
      oxide. METHODS AND RESULTS: The effluent from ventilated, Krebs-perfused rabbit
      lungs was passed directly over 3- to 4-mm rabbit aortic rings. Inhaled nitric
      oxide (150 ppm for 3 minutes) reduced pulmonary perfusion pressure, elevated by a
      continuous infusion of U46619, by 35 +/- 7% (mean +/- SEM, n = 5). Lung effluent
      from this series of experiments caused 40 +/- 13% relaxation of phenylephrine
      preconstricted aortic rings. When blood was added to the combined lung/ring
      perfusion cascade (final hemoglobin concentration, 1 g/dL), inhaled nitric oxide
      again significantly reduced pulmonary perfusion pressure, but the effluent now
      failed to relax the aortic rings (30 +/- 6% [control] versus 1.5 +/- 1% [blood]).
      Both reduction in pulmonary perfusion pressure and relaxation of the rings during
      nitric oxide exposure were unchanged from control values after discontinuing the
      blood infusion. CONCLUSIONS: The presence of hemoglobin, even in extremely small
      amounts, restricts the vasodilating effect of inhaled nitric oxide gas to the
      pulmonary circulation.

PMID- 8252702
TI  - Combined ADP and thromboxane A2 antagonism prevents cyclic flow variations in
      stenosed and endothelium-injured arteries in nonhuman primates.
AB  - BACKGROUND: This study was designed to test the hypothesis that clopidogrel, a
      potent inhibitor of platelet aggregation, can eliminate cyclic flow variations in
      stenosed and endothelium-injured coronary and femoral arteries in nonhuman
      primates. METHODS AND RESULTS: We studied five anesthetized, open-chest baboons.
      Blood flow velocity in the coronary and femoral arteries was monitored by pulsed
      Doppler flow probes placed around the arteries. Cyclic flow variations were
      established by mechanically injuring the endothelium of the arteries and by
      narrowing the arteries with external constrictors. Clopidogrel (10 to 20 mg/kg
      i.v. bolus plus 2.5 mg.kg-1 x h-1 continuous infusion) was administered 60
      minutes after cyclic flow variations were established. Clopidogrel abolished
      cyclic flow variations in the coronary and femoral arteries of all five baboons
      (frequency of cyclic flow variations, 0/h versus 14/h at baseline, P < .001).
      Then epinephrine was infused (maximum average dose, 2.2 micrograms.kg-1 x min-1
      i.v.). Epinephrine did not restore cyclic flow variations in the coronary or
      femoral arteries of any baboon. Before treatment with clopidogrel, ADP, collagen,
      and U46619, a thromboxane A2 mimetic, induced dose-dependent platelet aggregation
      in vitro. Serotonin, however, did not induce platelet aggregation in vitro.
      Clopidogrel given in vivo completely inhibited ADP-induced platelet aggregation
      and significantly diminished collagen- and U46619-induced platelet aggregation in
      vitro. CONCLUSIONS: Clopidogrel eliminates cyclic flow variations in stenosed and
      endothelium-injured coronary and femoral arteries of nonhuman primates at least
      in part by antagonizing the platelet proaggregatory effects of ADP and
      thromboxane A2.

PMID- 8252703
TI  - Electrical and mechanical alternans in canine myocardium in vivo. Dependence on
      intracellular calcium cycling.
AB  - BACKGROUND: Electrical and mechanical alternans are thought to result from a
      common cellular mechanism. To confirm this phenomenon in vivo and extend our
      understanding, we investigated the effects of temperature, verapamil, and
      caffeine on alternans in intact beating hearts. METHODS AND RESULTS: We recorded
      surface ECG, monophasic action potential (MAP) using suction electrodes, and left
      ventricular pressure (LVP). Alternans of MAP configurations and of LVP were
      evaluated in 20 dogs. MAPs were recorded from the apex, base, and midportion of
      the left ventricle with LVP. The hearts were driven from the left ventricular
      apex at a basic cycle length of 1000 milliseconds, and alternans was induced with
      an abrupt shortening of the cycle length to 400 milliseconds. MAPD30/100, the
      ratio between the MAP durations (MAPD) at 30% and 100% repolarization levels, was
      measured as an index of MAP configuration. The magnitude of MAP or LVP alternans
      was defined as the difference in MAPD30/100 or in LVP between the fifth and sixth
      paced beats. The magnitude of MAP alternans differed by recording site but
      correlated with activation time. Lowering the temperature increased the
      magnitude. MAP alternans was always associated with LVP alternans under control
      conditions. Verapamil significantly attenuated the magnitude of MAP alternans but
      did not change that of LVP alternans. Caffeine attenuated the magnitude of both
      MAP and LVP alternans. T wave alternans was suppressed by verapamil or caffeine.
      CONCLUSIONS: Activation time is one of the factors modifying electrical
      alternans. Delayed intracellular Ca2+ cycling plays a role in the concomitant
      occurrence of electrical and mechanical alternans.

PMID- 8252704
TI  - Differences in the electrophysiological response of canine ventricular epicardium
      and endocardium to ischemia. Role of the transient outward current.
AB  - BACKGROUND: Acute ischemia is known to produce more severe electrophysiological
      disturbances in canine ventricular epicardium than endocardium, although the
      mechanism for the differential sensitivity is still unresolved. Recent studies
      have demonstrated the presence of a prominent transient outward current (Ito) in
      ventricular epicardium but not endocardium. The present study was designed to
      test the hypothesis that the differential sensitivity of these two tissues to
      ischemia results, at least in part, from a more prominent Ito in epicardium than
      in endocardium. METHODS AND RESULTS: Isolated canine ventricular epicardial and
      endocardial tissues and myocytes were studied by standard microelectrode
      techniques. Simulated ischemia (hyperkalemia, hypoxia, and acidosis) abolished
      the action potential plateau and caused a 50% to 60% shortening of action
      potential duration in epicardium but only a 10% to 20% shortening in endocardium.
      4-Aminopyridine, an Ito inhibitor, restored the plateau in epicardium and reduced
      the dispersion of action potential duration between epicardium and endocardium.
      Stimulation protocols that minimized the contribution of Ito, such as
      acceleration of the stimulation rate or introduction of early premature beats,
      produced a paradoxical prolongation of the epicardial response caused by
      restoration of the action potential dome. Thus, ischemia-induced dispersion of
      repolarization was greatly diminished at rapid rates and after premature beats.
      Similar results were obtained in tissues and myocytes obtained from the same
      myocardial layers, suggesting that the differential sensitivities of epicardium
      and endocardium to ischemia are largely a result of inherent differences in
      cellular properties. CONCLUSIONS: Our data suggest that the presence of a
      prominent Ito in epicardium but not endocardium contributes importantly to the
      selective electrical depression of epicardium by simulated ischemia. The
      repolarizing influence of Ito serves to amplify the ischemia-induced changes in
      inward (ICa and INa) and outward (calcium-activated) currents. By facilitating
      loss of the dome in epicardium, Ito contributes to the development of a marked
      dispersion of repolarization between normal and ischemic epicardium and between
      epicardium and endocardium, thereby providing the electrophysiological substrate
      for the genesis of reentrant arrhythmias.

PMID- 8252705
TI  - Activation of calcium currents in cardiac myocytes by empty beta-adrenoceptors.
AB  - BACKGROUND: The cardiac calcium channel is known to be modulated by
      catecholamines via beta-adrenoceptors acting through intermediary GTP-binding
      regulatory proteins (G proteins). In biochemical studies on isolated membranes
      and reconstituted systems, it has been demonstrated that various G protein
      coupled receptors, including beta-adrenoceptors, can activate G proteins and also
      intracellular second messengers like cyclic AMP (cAMP) even in the absence of an
      agonist and that antagonists can block this empty receptor action. We examined
      electrophysiologically whether agonist-free beta-adrenoceptors can modulate L
      type calcium currents (ICa) in intact cardiac myocytes. METHODS AND RESULTS:
      Cardiomyocytes were isolated from ventricles of guinea pig and human hearts and
      from human right atrial appendage. The patch-clamp technique was applied in the
      single electrode mode to measure whole-cell ICa. Modulation of calcium currents
      by beta-adrenoceptor antagonists, without addition of an agonist, was studied in
      the absence and presence of the direct adenylyl cyclase activator forskolin and
      the cAMP analog adenosine cyclic 3',5'-monophosphorothioate (Sp-cAMPS). In the
      presence of forskolin (0.5 mumol/L), an agent known to sensitize the adenylyl
      cyclase signal transduction system for receptor regulation, addition of the beta
      1-selective antagonist atenolol and the nonselective antagonist propranolol (but
      not of the beta 2-selective antagonist ICI 118,551) caused a marked reduction of
      ICa in a concentration-dependent and stereoselective manner. The inhibitory
      effect of atenolol was reversible after washing out and was found to be half
      maximal and maximal (50% reduction) at about 50 and 300 nmol/L, respectively. In
      the absence of forskolin, inhibition of ICa by atenolol was markedly less (18% at
      10 mumol/L atenolol). Finally, in contrast to forskolin-stimulated currents,
      atenolol (1 mumol/L) did not reduce calcium currents activated by the protein
      kinase A activator Sp-cAMPS (0.1 mmol/L), causing by itself a similar increase in
      calcium currents as forskolin. CONCLUSIONS: In isolated guinea pig and human
      cardiomyocytes, agonist-free beta-adrenoceptors are functionally active and can
      stimulate L-type calcium currents, an effect blocked by receptor-specific
      antagonists.

PMID- 8252706
TI  - Circulating and tissue endothelin immunoreactivity in hypercholesterolemic pigs.
AB  - BACKGROUND: Hypercholesterolemia is characterized by a coronary vasoconstrictive
      response to the endothelium-dependent vasodilator acetylcholine. This abnormality
      may be due to reduced synthesis of endothelium-derived relaxing factor and/or
      enhanced synthesis and release of an endothelium-derived contracting factor.
      Endothelin is an endothelium-derived vasoconstrictor and mitogenic peptide that
      is present in normal plasma, and its circulating concentrations are elevated in
      disease states that are characterized by abnormal endothelium-dependent
      relaxation to acetylcholine. The current studies were designed to test the
      hypotheses that experimental hypercholesterolemia results in elevation of plasma
      and tissue endothelin immunoreactivity and that the abnormal acetylcholine-evoked
      coronary vasoconstriction in the hypercholesterolemic animals is associated with
      further elevation of plasma endothelin. METHODS AND RESULTS: Plasma
      concentrations and molecular forms of endothelin immunoreactivity were determined
      following 2% cholesterol diet for 4 months in pigs and during intracoronary
      acetylcholine administration. Second, we assessed the presence of endothelin in
      the coronary vascular wall by using immunohistochemistry. Hypercholesterolemia
      elevated plasma endothelin concentration and enhanced coronary artery tissue
      endothelin immunoreactivity. The endothelium-dependent vasodilator acetylcholine
      further increases plasma endothelin in hypercholesterolemia in association with
      coronary vasoconstriction. The predominant molecular form of endothelin in
      hypercholesterolemia is the biological active endothelin-1. CONCLUSIONS: This
      study suggests a role for endothelin as an early participant and a marker for the
      endothelial dysfunction in hypercholesterolemia as well as a participant in the
      atherogenic process.

PMID- 8252707
TI  - Left ventricular diastolic chamber stiffness and intramyocardial coronary
      capacitance in isolated dog hearts.
AB  - BACKGROUND: Because the myocardium is perfused primarily during diastole, changes
      in diastolic properties of the left ventricle (LV) should influence the
      intramyocardial circulation. METHODS AND RESULTS: We examined the influence of LV
      diastolic properties on the magnitude and localization of intramyocardial
      coronary capacitance by analyzing the coronary pressure-venous flow relation in
      isolated, isovolumic dog heart preparations. After sudden occlusion of the left
      coronary artery during a long diastole, we measured precapacitance and
      postcapacitance resistances (RPRE and RPOST) and calculated intramyocardial
      coronary capacitance (CIM) from RPOST and the time constant of the coronary
      venous flow decay. Using this method, we characterized the effects of coronary
      vasodilation, LV diastolic volume, and LV diastolic chamber stiffness on the
      coronary circulation. The magnitude of CIM increased from 0.09 +/- 0.01 to 0.24
      +/- 0.20 mL.mm Hg-1 x 100 g-1 (P < .01) after adenosine-induced vasodilation,
      whereas both RPOST and RPRE decreased significantly. The ratio of RPOST to
      RPRE+RPOST decreased from 0.35 +/- 0.02 to 0.23 +/- 0.02 (P < .01), suggesting
      redistribution of CIM to the distal portion of the coronary vascular tree. An
      increase in LV volume and wall stress was imposed to increase LV diastolic
      pressure from 2 +/- 0.1 to 25 +/- 1 mm Hg: this increased RPOST significantly but
      not RPRE and decreased the magnitude of CIM. The resistance ratio did not change
      significantly. Increased LV diastolic chamber stiffness induced by hypoxic
      perfusion (isovolumic LV diastolic pressure increased from 11 +/- 1 to 28 +/- 1
      mm Hg) raised RPOST and decreased the magnitude of CIM from 0.32 +/- 0.12 to 0.17
      +/- 0.04 mL.mm Hg-1 x 100 g-1 (P < .05). The resistance ratio increased
      significantly from 0.21 +/- 0.05 to 0.33 +/- 0.05 with increased LV diastolic
      chamber stiffness. Adjustment of LV diastolic volume to lower diastolic pressure
      to 10 +/- 1 mm Hg did not alter these changes significantly, suggesting that an
      intrinsic increase in myocardial stiffness played a major role in these changes.
      CONCLUSIONS: Extravascular compression by raised LV diastolic volume and/or
      increased LV diastolic chamber stiffness acted mainly on coronary vessels that
      determine intramyocardial capacitance and postcapacitance resistance.

PMID- 8252708
TI  - Sudden death prevention in patients with advanced ventricular dysfunction.

PMID- 8252709
TI  - Images in cardiovascular medicine. A heavily calcified left atrial myxoma.

PMID- 8252710
TI  - A 63-year-old man who developed severe abdominal pain after thrombolytic therapy.

PMID- 8252711
TI  - Idiopathic left ventricular tachycardia. Cure by radiofrequency ablation.

PMID- 8252712
TI  - P-wave signal averaging. High tech or an expensive alternative to the standard
      ECG?

PMID- 8252713
TI  - Guidelines for percutaneous transluminal coronary angioplasty. A report of the
      American Heart Association/American College of Cardiology Task Force on
      Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on
      Percutaneous Transluminal Coronary Angioplasty).

PMID- 8252714
TI  - Rationale of the diet-heart statement of the American Heart Association. Report
      of the Nutrition Committee.

PMID- 8252715
TI  - Serum phospholipases A2 in inflammatory diseases.
AB  - Phospholipase A2 (EC 3.1.1.4; PLA2) is detected in serum by determination of
      either the catalytic activity of the enzyme or the concentration of the enzyme
      protein by immunoassays. The most sensitive methods for determining PLA2
      catalytic activity are radiometric assays, with a substrate of synthetic
      phospholipid (e.g., phosphatidylcholine or phosphatidylethanolamine) containing a
      14C- or 3H-labeled fatty acid at the sn-2-position. Membranes of autoclaved
      Escherichia coli grown in the presence of radioactive oleic acid may also be used
      as a substrate. The released fatty acids are separated from the unreacted
      substrate and quantified by liquid scintillation counting. PLA2 catalytic
      activities are increased in serum in sepsis, acute pancreatitis, peritonitis,
      multiple injuries, rheumatoid arthritis, and other arthropathies. Immunoassays-
      radioimmunoassay, enzyme-linked immunosorbent assay, or time-resolved
      fluoroimmunoassay--are based on the use of either polyclonal or monoclonal
      antibodies to purified PLA2s. Specific assays have been developed for both
      pancreatic group I PLA2 (PLA2-I) and nonpancreatic group II PLA2 (PLA2-II). The
      cellular source of PLA2-I in serum is the pancreatic acinar cell. Increased serum
      PLA2-I values have been reported in acute pancreatitis, pancreatic cancer, and
      abdominal trauma. Increased PLA2-II values are found in conditions involving
      inflammation, e.g., sepsis, infections, acute pancreatitis, various forms of
      arthritis, cancer, complications of pregnancy, and postoperative states. Good
      correlations have been found in serum samples between the catalytic activity of
      PLA2 and the concentration of PLA2-II but not PLA2-I. PLA2-II may represent an
      acute-phase protein. The cellular source of the PLA2-II in serum is unknown; it
      is present in large amounts in cartilage and Paneth cells, prostatic gland cells,
      seminal fluid, lacrimal gland cells, and tears, but cannot be demonstrated by
      immunohistochemical or immunochemical methods in inflammatory cells.

PMID- 8252716
TI  - Mechanism of fructosamine assay: evidence against role of superoxide as
      intermediate in nitroblue tetrazolium reduction.
AB  - We studied the chemistry of the fructosamine assay for glycated serum proteins by
      using the model Amadori compound N alpha-formyl-N epsilon-fructoselysine (fFL),
      an analog of glycated lysine residues in protein. Free lysine was formed at
      approximately 70% yield during a standard 20-min incubation of fFL with alkaline
      nitroblue tetrazolium (NBT) at 37 degrees C. Although superoxide dismutase (SOD;
      EC 1.15.1.1) and catalase (EC 1.11.1.6) decreased the yield of the product,
      monoformazan dye (MF+), the yield of MF+ was slightly greater under anaerobic
      than aerobic conditions, excluding a role for superoxide as an intermediate in
      the reduction of NBT during the fructosamine assay. SOD added to diabetic
      patients' sera at physiological concentrations also caused a significant
      (approximately 50%) inhibition of MF+ formation. This inhibition was reduced by
      addition of nonionic detergents, which contain organic peroxide inhibitors of
      SOD, to the fructosamine reagent. Overall, these data indicate that the Amadori
      compound is the direct reductant of NBT in the fructosamine assay and that
      superoxide is not an intermediate in the reaction. The inhibitory effects of SOD
      and catalase are most likely the result of oxygen regeneration in the assay
      mixture.

PMID- 8252717
TI  - Effect of thyroid function on concentrations of lipoprotein(a)
AB  - The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was
      analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30
      cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after
      normalization of the thyroid state. Treatment of hyperthyroidism increased the
      mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P < 0.002); at the same
      time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to
      3.7 mmol/L, P < 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17
      g/L, P < 0.0005). In hypothyroidism, the opposite changes were observed: mean
      Lp(a) decreased from 136 to 114 mg/L (10%, P < 0.02), LDL-C from 4.6 to 3.9
      mmol/L (13%, P < 0.01), and apo B from 1.51 to 1.20 g/L (14%, P < 0.01). Although
      the changes in Lp(a) concentrations did correlate with changes of LDL-C during
      treatment of hyperthyroidism (r = 0.43, P < 0.05), and with changes in apo B
      during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P < 0.05), we
      observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state.
      These data cannot rule out the possibility that the thyroid hormone-induced
      increase in LDL-C receptor activity was responsible for the decreased
      concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30%
      of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with
      those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C
      receptor-independent pathway, the present data suggest a direct effect of thyroid
      hormones on Lp(a) synthesis.

PMID- 8252718
TI  - Rapid, direct enzyme immunoassay of 11-keto-thromboxane B2 in urine, validated by
      immunoaffinity/gas chromatography-mass spectrometry.
AB  - We have developed a direct enzyme immunoassay (EIA) for quantifying
      immunoreactive 11-keto-thromboxane B2 (iKTXB) in unprocessed human urine. Cross
      reactivity with other thromboxane metabolites and prostanoids was negligible.
      Analytical recovery of 11-keto-TXB2 in urine specimens was 97.4% to 99.8%. Total
      imprecision for two clinical specimens was 8.5% and 12.2%. Intake of
      acetylsalicylic acid decreased the measured concentration of iKTXB.
      Cardiopulmonary bypass, a procedure known to activate platelets, increased the
      mean excretion rate of iKTXB 10-fold. Simultaneous gas chromatography-mass
      spectrometry analysis of 11-keto-TXB2 and 11-keto-2,3-dinor TXB2 in urine
      specimens (n = 17) from healthy subjects indicated that urinary iKTXB
      concentrations measured by EIA represented a sum of the two 11-keto metabolites.
      We conclude that the direct EIA is sufficiently sensitive, rapid, simple, and
      specific to allow screening for alterations in thromboxane biosynthesis in
      patients.

PMID- 8252719
TI  - Predicting behavior of an enzyme-linked immunoassay model by using commercially
      available neural network software.
AB  - Setting up new immunoassays can be a laborious and expensive task. A relatively
      new form of multivariate analysis known as neural networks can be applied to this
      problem with potential savings in reagents and technician time. Neural network
      software programs for personal computers are now available. We applied one such
      software package (Brainmaker) to a model ELISA system for measuring human serum
      albumin. Random combinations of four variable ELISA conditions (antigen
      concentration, primary and secondary antibody titers, and time for chromagen
      development) were used to train a three-layered feed-forward network. The trained
      network was then used to predict measured absorbances as a function of the four
      input variables in separate cross-validation sets. The network adequately
      predicted the effect of the input variables on the absorbance produced. With use
      of such methods, optimal conditions for the linear dependence of absorbance on
      antigen concentration can be evaluated on the computer rather than in the
      laboratory, with subsequent savings of time and money.

PMID- 8252720
TI  - Antibodies to casein kinase II in sera of patients with mixed connective tissue
      disease: evaluation with recombinant proteins.
AB  - In this study we determined the prevalence of autoantibodies against casein
      kinase II (CKII) in patients positive for anti-70K marker antibodies, which is
      indicative of mixed connective tissue disease. An anti-CKII ELISA was established
      with the use of bacterially expressed recombinant CKII proteins. Eight out of 52
      anti-70K-positive sera (15%) were positive for anti-CKII antibodies, which
      recognized preferentially the CKII alpha subunit. All control sera (n = 52) were
      anti-CKII negative. Thus, the occurrence of anti-CKII antibodies may be of value
      for differential diagnosis.

PMID- 8252721
TI  - Densitometric determination of urinary 4-hydroxy-3-methoxymandelic acid
      (vanillylmandelic acid).
AB  - We propose a simple and precise densitometric method for measuring
      vanillylmandelic acid (VMA). The method comprises direct urine application, thin
      layer chromatographic (TLC) separation, postchromatographic derivatization, and
      in situ reading of the formed derivative at 560 nm. Quantitation was done by
      measuring peak area with a computer-controlled TLC Scanner and applying a five
      point calibration function. The calibration function was 7.57-49.23 mumol/L. This
      method was used to determine urinary concentrations of excreted VMA;
      concentrations ranged from 4.84 to 56.06 mumol/day.

PMID- 8252722
TI  - Optimal collection and storage conditions for catecholamine measurements in human
      plasma and urine.
AB  - Improvements in methodologies for measuring concentrations of catecholamines (CA)
      have led to an increasing use of these compounds as markers in the screening of
      patients and in long-term clinical trials. Because of the associated logistical
      problems, we have investigated the unresolved question of optimal conditions for
      sample preparation and for storage of plasma and urine samples. Results show that
      blood should be centrifuged within 1 h after collection; the use of a
      refrigerated centrifuge is not necessary. Once plasma is prepared, CA are stable
      for 1 day at 20 degrees C, 2 days at 4 degrees C, 1 month at -20 degrees C (or 6
      months with added glutathione), and up to 1 year at -70 degrees C. CA are stable
      at 4 degrees C for 1 month in unpreserved urine and for 4 months in urine
      preserved with EDTA and sodium metabisulfite. In acidified urine, CA were nearly
      unchanged after 1 year at 4 and -20 degrees C.

PMID- 8252723
TI  - Heterologous double-determinant immunoradiometric assay CA 125 II: reliable
      second-generation immunoassay for determining CA 125 in serum.
AB  - The new CA 125 II (Centocor) serum assay utilizing the M11 mouse monoclonal
      antibody as capture antibody and OC125 as tracer antibody, was investigated for
      its technical and clinical performance against the original CA 125 assay. The CA
      125 II test revealed a quadruple increase in signal-to-noise ratio, good intra-
      and interassay precision (with CVs < 5% and 7%, respectively), improved dilution
      linearity, and a minimal detectable dose of 0.38 units/mL. Sera were obtained
      from healthy females (n = 192), women with benign conditions (n = 208), and
      patients with various cancers (n = 379). Both assays measured highly similar CA
      125 distributions with equal reference ranges and nearly identical positivity (>
      35 units/mL) rates, resulting in similar receiver-operating characteristic curves
      and monitoring graphs. Linear regression analysis of results by the two assays
      (CA 125 = x, CA 125 II = y) in ovarian cancer patients showed, for CA 125 assay
      values between 0 and 1000 units/mL, a slope of 1.00 and a y-intercept of 12.6 (n
      = 254, r = 0.8617, P < 0.0001). The heterologous CA 125 II assay appeared to be
      more accurate in patients who had human anti-mouse antibodies after
      immunoscintigraphy. The CA 125 II immunoradiometric assay is sensitive and
      reliable for measuring serum CA 125, and fully retains the cutoff values of 35
      and 65 units/mL that were defined with the original CA 125 immunoradiometric
      assay.

PMID- 8252724
TI  - Free cortisol in serum assayed by temperature-controlled ultrafiltration before
      fluorescence polarization immunoassay.
AB  - A method is described for a temperature-controlled ultrafiltration procedure to
      measure free cortisol in serum. A special thermometer with a sensor was
      developed, measuring the temperature directly in the ultrafiltration device. The
      sensor is screwed on the axis of the centrifuge rotor, and the centrifuge is
      placed in a temperature-controlled box so that the temperature of the sample is
      kept at 37 degrees C +/- 0.1 degrees C. The overall CV of the free cortisol assay
      ranges from 2.2% to 11.4%, of which the ultrafiltration contributes only 2.2
      3.6%. Increasing amounts of cortisol-binding protein, as found in women using
      estrogen-containing oral contraceptives, have minor but significant effects on
      the free cortisol concentrations in serum. Serum free cortisol concentrations in
      a reference population (n = 114; central 95 percentiles) were 12-43 nmol/L (4
      9.5% of total cortisol); in the group of the oral-contraceptive users (n = 27),
      the reference interval was 11-53 nmol/L (1.5-4.5%).

PMID- 8252725
TI  - Optimized steps in fluorometric determination of thiobarbituric acid-reactive
      substances in serum: importance of extraction pH and influence of sample
      preservation and storage.
AB  - A simple, reliable, and reproducible fluorometric method for measuring
      thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on
      the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of
      TBARS was complete at pH 2.4-2.6, but extraction with n-butanol proved complete
      only at lower pH, i.e., 1.6-1.7. Analytical recoveries of MDA added to serum were
      94%-101%; within- and between-run CVs were 2.4-3.6% and 4.6-5.5%; and the
      detection limit for TBARS in serum was 0.10 mumol/L. Optimized conditions
      included: (a) collection of either serum or heparinized plasma, (b) preservation
      from in vitro autoxidation by glutathione and EDTA, and (c) storage at -20
      degrees C up to 35 days. The mean (+/- SD) TBARS concentration in 47 healthy
      adults was 1.01 (0.21) mumol/L; no sex-related difference was observed. Higher
      concentrations were measured in patients with renal insufficiency undergoing
      hemodialysis and in patients with insulin-dependent diabetes, chronic
      pancreatitis, or liver cirrhosis.

PMID- 8252726
TI  - Expression of plasma fatty acid data in studies of cardiovascular disease risk:
      concentration or percentage?

PMID- 8252727
TI  - Immunochemiluminometric and third-generation assays of thyrotropin.

PMID- 8252728
TI  - Direct determination of cyclic guanosine monophosphate in plasma.

PMID- 8252729
TI  - Semiquantitative determination of fecal leukocyte esterase by a dip-and-read
      assay.

PMID- 8252730
TI  - Calibration of the CYCLO-Trac SP cyclosporine radioimmunoassay.

PMID- 8252731
TI  - Improved colorimetric determination of urinary thiosulfate to study intermediate
      sulfur metabolism in humans.

PMID- 8252732
TI  - Simple colorimetric method for determination of peroxide.

PMID- 8252733
TI  - Plastic vs glass SST evacuated serum-separator blood-drawing tubes for
      endocrinologic analytes.

PMID- 8252734
TI  - Circulating normal proalbumin.

PMID- 8252735
TI  - Between-method carryover for iron and triglyceride assays on Hitachi 717
      analyzers avoided by a software-controlled wash.

PMID- 8252736
TI  - Alcohol testing in the clinical laboratory: alternative remedies.

PMID- 8252737
TI  - The sick euthyroid syndrome: changes in thyroid hormone serum parameters and
      hormone metabolism.

PMID- 8252738
TI  - Thyroid hormone therapy and the skeleton.

PMID- 8252739
TI  - Bone mineral density in patients with endogenous subclinical hyperthyroidism: is
      this thyroid status a risk factor for osteoporosis?
AB  - OBJECTIVE: The aim of the present study was to elucidate whether endogenous
      subclinical hyperthyroidism due to a solitary autonomously functioning thyroid
      nodule affects bone metabolism and is a risk factor for osteoporosis. DESIGN: In
      a cross-sectional study measurements of bone mineral density were performed in
      premenopausal and post-menopausal women. Patients were categorized into non-toxic
      nodular goitre (n = 32), subclinical hyperthyroid (n = 37) and toxic solitary
      autonomous thyroid nodule (n = 22) subgroups and the results were compared with
      those of sex and age-matched control reference population (n = 68). MEASUREMENTS:
      Lumbar spine and femoral neck bone mineral densities were measured by dual energy
      X-ray absorptiometry. Single-photon absorptiometry was applied to the measurement
      of bone mineral content in the midshaft of the radius. RESULTS: In the non-toxic
      nodular goitre group, bone densities for all the scanned sites did not differ
      from the sex and age-matched reference population. At the L2-4 scanning site a
      significant decrease in the bone mineral density could be observed only in the
      toxic nodular goitre group and this decrease was more marked in the
      postmenopausal (P < 0.001) than in the premenopausal females (P < 0.05). At the
      femoral neck and midshaft radius the mean densitometric values were slightly, but
      significantly, lower only in the post-menopausal subclinical hyperthyroid group
      compared with the reference population (P < 0.01). The bone mineral density of
      the femoral neck, as well as the bone mineral content of the midshaft radius, was
      significantly decreased in both the premenopausal and post-menopausal patients
      with a toxic solitary nodule. CONCLUSION: This study indicates that the bone
      mineral density of the lumbar spine, femoral neck and the midshaft of the radius
      are not significantly decreased in premenopausal patients with endogenous
      subclinical hyperthyroidism resulting from a solitary autonomously functioning
      thyroid nodule. Conversely, findings hint at the possibility that long-lasting
      endogenous subclinical hyperthyroidism may be a contributing factor to the
      development of osteoporosis in some post-menopausal women, mostly at sites where
      cortical bone preponderates.

PMID- 8252740
TI  - Suppressed TSH levels secondary to thyroxine replacement therapy are not
      associated with osteoporosis.
AB  - OBJECTIVE: Recent studies have suggested that patients receiving thyroxine are at
      increased risk of osteoporosis. We set out to measure bone mineral densities in
      two groups of post-menopausal women receiving thyroxine replacement therapy
      (those with serum TSH levels persistently suppressed or non-suppressed) and to
      compare the results in both groups with those of the local control population.
      DESIGN: Cross-sectional study. PATIENTS: Seventy-eight post-menopausal women who
      had been treated with thyroxine for primary autoimmune or idiopathic
      hypothyroidism for a minimum of 5 years, 44 with TSH persistently suppressed and
      34 non-suppressed. One hundred and two control subjects. MEASUREMENTS: Forearm
      bone mineral density at proximal and distal sites as measured by single-photon
      absorptiometry. RESULTS: Results were expressed as Z-scores, i.e. number of
      standard deviations from the mean of a 5-year age-band from the local control
      population. Mean Z-scores at proximal and distal sites for the non-suppressed
      patients were -0.03 and -0.07 and for the suppressed patients were -0.20 and 
      0.25, representing a decrease in bone mineral density of at most 5% in the
      suppressed patients. The differences between the three groups were not
      statistically significant. CONCLUSION: In this patient population, the reduction
      in bone mineral density due to thyroxine is small. It is unlikely to be of
      clinical significance and should not on its own be an indication for reduction of
      thyroxine dose in patients who are clinically euthyroid.

PMID- 8252741
TI  - Thyroxine suppressive therapy decreases bone mineral density in post-menopausal
      women.
AB  - OBJECTIVE: Hyperthyroidism is associated with increased bone turnover and
      decreased bone mass. This study aimed to evaluate the bone mineral density (BMD)
      of post-menopausal women on long-term thyroxine suppressive therapy. DESIGN: An
      age and sex-matched cross-sectional study. PATIENTS: Thirty-four post-menopausal
      women with carcinoma of thyroid, post total thyroidectomy and 131I ablation, on L
      T4 for 12.2 +/- 6.6 years (mean +/- SD). Controls were 34 age-matched healthy
      Southern Chinese women. MEASUREMENTS: Total body and regional BMDs were
      determined by dual-energy X-ray absorptiometry. Bone turnover was assessed by
      biochemical markers. RESULTS: In the thyroxine treated group, total body mineral
      content was significantly lower than the controls (1652 +/- 356 vs 1994 +/- 270 g
      mean +/- SD, P < 0.005). They also had lower BMDs in the lumbar spine, femoral
      neck, trochanter and Ward's triangle (0.75 +/- 0.15 vs 0.92 +/- 0.16 g/cm2, P <
      0.005; 0.62 +/- 0.12 vs 0.70 +/- 0.12 g/cm2, P < 0.01; 0.55 +/- 0.14 vs 0.63 +/-
      0.15 g/cm2, P < 0.001; 0.55 +/- 0.14 vs 0.63 +/- 0.14 g/cm2, P < 0.005
      respectively.) The thyroxine treated group also had higher serum alkaline
      phosphatase and osteocalcin levels as well as urinary hydroxyproline excretion,
      suggesting that they had high turnover bone loss. However, the Z-scores of the
      various regional BMDs were correlated only with the serum osteocalcin level and
      showed no correlation with the serum thyroxine level or with the dosage or
      duration of thyroxine treatment. CONCLUSION: Long-term thyroxine suppressive
      therapy was associated with bone loss and preventive therapy may be indicated in
      these post-menopausal women at risk of osteoporosis.

PMID- 8252742
TI  - A long-term follow-up study of patients with non-toxic diffuse goitre in Japan.
AB  - OBJECTIVE: Although non-toxic diffuse goitre is a common disorder, little is
      known of the clinical course of patients. We therefore decided to investigate the
      long-term clinical outcome of patients with non-toxic diffuse goitre. DESIGN: A
      retrospective study. PATIENTS: Of 850 patients with non-toxic diffuse goitre who
      met our criteria and were seen in our thyroid clinic between 1977 and 1985, 108
      who had been followed for from 5 to 14 years (mean 8 years) were entered in this
      study. All patients fulfilled our criteria having soft diffuse goitres, normal
      serum TSH and T4 concentrations, and undetectable antithyroglobulin and
      antithyroid microsomal antibodies. MEASUREMENTS: A family history of thyroid
      disease was obtained and the occurrence of Graves' ophthalmopathy was noted.
      Serum TSH and T4 concentrations, and antithyroglobulin and antithyroid microsomal
      antibodies were measured during the follow-up period. Thyroidal radioactive
      iodine uptake (RAIU), serum free T4 and free T3 concentrations, and TSH binding
      inhibitory immunoglobulin (TBII) activities were determined in all patients who
      were subsequently found to have abnormal serum TSH or T4 concentrations or signs
      of Graves' ophthalmopathy. RESULTS: Thirty-six of the 108 patients (33%) had a
      family history of autoimmune thyroid disease. Elevated serum T4 or free T4
      concentrations and depressed serum TSH concentrations were found in six patients
      during the follow-up period. Hyperthyroid Graves' disease was diagnosed in four
      of the six patients, subacute thyroiditis in one, and transient post-partum
      thyrotoxicosis in one. Hypothyroidism was found in one patient who was diagnosed
      as having transient post-partum hypothyroidism. Euthyroid Graves' disease was
      diagnosed in one patient. Furthermore, six of these eight patients had a family
      history of autoimmune thyroid disease in first-degree relatives. CONCLUSION:
      During a prolonged follow-up period of patients with non-toxic diffuse goitre,
      Graves' disease was found in five of 108 patients (four hyperthyroid Graves' and
      one euthyroid Graves'), post-partum thyroid dysfunction in two, and subacute
      thyroiditis in one. Six of these eight patients had a family history of
      autoimmune thyroid disease in first-degree relatives. Long-term follow-up is
      necessary for patients with non-toxic diffuse goitre, especially those who have a
      family history of autoimmune thyroid disease.

PMID- 8252743
TI  - Variable androgen sensitivity in relationship to hirsutism and acne.

PMID- 8252744
TI  - Two different pathogenetic mechanisms may play a role in acne and in hirsutism.
AB  - OBJECTIVE: Acne is one of the most common skin disorders. Androgens are known to
      play an important and possibly central role. Androgens secreted from ovaries and
      adrenal glands (androstenedione, dehydroepiandrosterone and its sulphate,
      testosterone) and target tissue-produced androgens (testosterone and its 5 alpha
      reduced metabolite, dihydrotestosterone) have been implicated. Although the
      sebaceous gland and the hair follicle form a single morphological entity, the
      pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus
      leading to the supposition that these two structures may have different degrees
      of sensitivity to similar androgenic stimulation. DESIGN AND PATIENTS: To
      determine whether acne and hirsutism are the clinical expression of a different
      androgen metabolism at target tissue levels we studied 90 randomly selected
      patients who came to our Out-patient Department for diagnosis and treatment
      during the last 2 years with isolated acne of mild to severe degree and 52
      patients with idiopathic hirsutism without acne or history of acne. Twenty-four
      women without acne or hirsutism and without a history of endocrine disease were
      studied as controls. MEASUREMENTS: In both groups of patients, plasma levels of
      sex hormone binding globulin, of dihydrotestosterone, and of 3 alpha
      androstanediol and of its glucuronide were evaluated. In all patients the
      percentage of free testosterone and the testosterone/sex hormone binding globulin
      ratio were also calculated. RESULTS: Patients with acne and those with isolated
      hirsutism showed significantly decreased sex hormone binding globulin plasma
      levels. The values of the percentage free testosterone and those of the
      testosterone/sex hormone binding globulin ratio were, on the contrary, higher
      with respect to the controls, although there were no statistically significant
      differences between the two groups. Significantly increased plasma levels of
      dihydrotestosterone with respect to the controls were observed in patients with
      acne or in those with hirsutism. However, while all patients with hirsutism
      showed increased plasma values of 3 alpha-androstanediol and its glucuronide, all
      patients with acne showed plasma levels within the normal range, independently of
      the precursor plasma levels. CONCLUSIONS: Our results demonstrate that
      dihydrotestosterone is further reduced to 3 alpha-androstanediol and its
      glucuronide only in hirsute patients but not in acne patients. These results
      suggest that dihydrotestosterone may undergo different metabolic pathways at skin
      levels and support the hypothesis that the two clinical manifestations may be the
      expression of the different metabolic fate of dihydrotestosterone itself.
      Moreover, our results demonstrate that 3 alpha-androstanediol and its glucuronide
      cannot be used as plasma markers of target-tissue produced androgens in all
      hyperandrogenic conditions.

PMID- 8252745
TI  - Plasma 19-hydroxyandrostenedione is elevated in patients with high renin
      essential hypertension.
AB  - OBJECTIVES: We have reported that 19-hydroxyandrostenedione (19-OH-A-dione)
      functions as an amplifier of the sodium-retaining and hypertensive action of
      aldosterone. We therefore measured 19-hydroxyandrostenedione in hypertensive
      patients. PATIENTS AND MEASUREMENTS: We studied 53 normal male control subjects
      and 63 male patients with essential hypertension (48 patients with normal renin
      essential hypertension and 15 patients with high renin essential hypertension).
      Plasma 19-OH-A-dione levels were measured by RIA. RESULTS: Plasma 19-OH-A-dione
      concentrations in control subjects and patients with normal and high renin
      essential hypertension were 115 +/- 46 (mean +/- SD), 112 +/- 49 and 201 +/- 79
      pmol/l, respectively. Patients with high renin essential hypertension showed
      significantly higher 19-OH-A-dione concentrations than did control subjects. The
      evaluation of the correlation between plasma 19-OH-A-dione concentrations and
      plasma renin activity revealed that plasma 19-OH-A-dione concentrations in
      hypertensive subjects rose gradually with an increase in plasma renin activity.
      Therefore, a significant correlation was found between plasma renin activity and
      plasma 19-OH-A-dione (r = 0.586, P < 0.001). In contrast, in control subjects, no
      significant correlation was found between plasma renin activity and plasma 19-OH
      A-dione (r = 0.059, P > 0.05). CONCLUSIONS: The secretion of 19-OH-A-dione from
      the adrenal cortex is under the control of the renin-angiotensin system in
      hypertensives but not in normotensives.

PMID- 8252746
TI  - Effects of different oral oestrogen formulations on insulin-like growth factor-I,
      growth hormone and growth hormone binding protein in post-menopausal women.
AB  - OBJECTIVE: Insulin like growth factor-I (IGF-I) levels in post-menopausal women
      are reduced by oral administration of the synthetic oestrogen ethinyl oestradiol
      but increased by transdermal delivery of 17 beta-oestradiol. Since these
      oestrogen types are different, the aim of this study was to clarify whether
      reduction in IGF-I is a specific effect of ethinyl oestradiol or common to other
      oral oestrogen formulations. DESIGN: Randomized cross-over study comparing one
      month of treatment with ethinyl oestradiol (20 micrograms), conjugated equine
      oestrogen (1.25 mg Premarin) and oestradiol valerate (2 mg). SUBJECTS: Six
      healthy post-menopausal women, age 60.3 +/- 5.6 years. MEASUREMENTS: Mean 24 hour
      GH (from hourly sampling), IGF-I, GH binding protein (GHBP), pituitary (LH, FSH)
      and hepatic function (SHBG and angiotensinogen) were measured. RESULTS: All three
      oestrogen formulations resulted in a significant reduction in IGF-I levels
      compared to baseline and significant elevations of GH and GHBP (P < 0.05). The
      percentage increase in GH during oestrogen treatment was significantly related to
      the percentage decrease in IGF-I levels (P = 0.04). All three oestrogen
      formulations resulted in significant suppression of LH and FSH and induction of
      the hepatic proteins, SHBG and angiotensinogen (P < 0.05). GHBP increased in
      parallel with other hepatic proteins. CONCLUSIONS: Reduction in IGF-I levels is
      an intrinsic effect of oral oestrogen therapy and increased GH levels may occur
      as a result of reduced feedback inhibition by IGF-I. Since GHBP activity is not
      changed by transdermal oestrogen, we conclude that the liver is a major source of
      circulating GHBP and that GHBP is an oestrogen sensitive protein.

PMID- 8252747
TI  - Effect of oestrogen status on serum levels of growth hormone-binding protein and
      insulin-like growth factor-I in non-pregnant and pregnant women.
AB  - OBJECTIVE: Since there appears to be a relationship between circulating
      oestrogens and growth hormone, we have investigated the effect of the oestrogen
      status of adult women on serum levels of GHBP and IGF-I. DESIGN AND PATIENTS: The
      investigation was performed on serum samples of 14 spontaneously menstruating
      women, 10 women taking oral contraceptives containing 20-50 micrograms
      ethinyloestradiol, and 30 pregnant women at different stages of pregnancy.
      MEASUREMENTS: Serum levels of GHBP were measured by HPLC gel filtration and IGF-I
      levels were measured by RIA after acid-ethanol extraction. RESULTS: In the
      spontaneously menstruating women the mean +/- SD serum level of GHBP was 34.6 +/-
      6.7% and of IGF-I 30 +/- 7 nmol/l. Serum GHBP levels were negatively (r = -0.67;
      P < 0.01) and IGF-I levels were positively related (r = 0.69; P < 0.01) to serum
      oestradiol concentrations. In the women taking oral contraceptives serum levels
      of GHBP were 47.0 +/- 7.4%. This was significantly (P < 0.001) higher than in
      spontaneously menstruating women. In contrast, IGF-I levels were not different
      from those obtained in spontaneously menstruating women. In the pregnant women,
      the mean +/- SD serum level of GHBP was not different from that observed in non
      pregnant spontaneously menstruating women. Polynomial regression analysis,
      however, showed a significant (P = 0.01) second-order relationship between the
      duration of pregnancy and serum GHBP levels, with increasing levels during the
      first half of pregnancy and decreasing levels thereafter. Serum concentrations of
      IGF-I increased during the second half of pregnancy and were significantly (P <
      0.005) elevated in the third trimester. CONCLUSIONS: In non-pregnant women the
      endogenous oestrogen status seems to modulate negatively GHBP levels and
      positively IGF-I levels, whereas oral oestrogen administration, in contrast,
      increases serum levels of GHBP without modification of IGF-I levels. During
      pregnancy serum GHBP levels increase slightly during the first half of pregnancy
      and decrease thereafter, whereas IGF-I concentrations increase during the second
      part of pregnancy. The oestrogen status of women has a complex effect on serum
      concentrations of GHBP and IGF-I and has therefore to be taken into account when
      evaluating serum levels of GHBP and IGF-I.

PMID- 8252748
TI  - Impact of 2 weeks high dose growth hormone treatment on basal and insulin
      stimulated substrate metabolism in humans.
AB  - OBJECTIVE: Short-term, high dose growth hormone (GH) treatment has been advocated
      in many catabolic disease states. It is likely that some of the anabolic effects
      of GH are mediated through activation of lipolysis, but the metabolic impact of
      therapeutically relevant GH exposure is not known in detail. The present study
      was accordingly designed to assess the effects of such GH exposure on basal and
      insulin stimulated intermediary metabolism. DESIGN, PATIENTS AND MEASUREMENTS:
      Six healthy young females were examined following daily injections of GH (12
      IU/day) or saline for 2 weeks in a placebo controlled design. Each study
      consisted of a 3 hour basal period and a 2 hour hyperinsulinaemic euglycaemic
      clamp. RESULTS: GH treatment caused (1) increased levels of IGF-I (382 +/- 46 vs
      294 +/- 22 micrograms/l, P < 0.05) and (2) increased basal values of free fatty
      acids (714 +/- 40 (GH) vs 634 +/- 64 (placebo) mumol/l, P < 0.05), 3
      hydroxybutyrate (118.3 +/- 42.8 (GH) vs 57.7 +/- 21.6 (placebo) mumol/l, P <
      0.05), glycerol (54.3 +/- 8.2 (GH) vs 41.4 +/- 8.4 (placebo) mumol/l, P < 0.05)
      and forearm uptake of 3-hydroxybutyrate, together with increments of plasma
      glucose (5.28 +/- 0.11 (GH) vs 4.87 +/- 0.16 (placebo) mmol/l, P < 0.05). Basal
      forearm uptake of glucose, isotopically determined glucose turnover and serum
      levels of GH, insulin and C-peptide were unaltered. During the clamp GH treatment
      was associated with (1) a 40% decrease in the administered amount of glucose (M
      value) (P < 0.05) and (2) a 70% decrease in forearm glucose uptake (P < 0.05).
      Indirect calorimetry revealed a 15% increase in resting energy expenditure (P <
      0.05) and a decreased basal respiratory exchange ratio (0.75 (GH) vs 0.80
      (placebo), P < 0.05), presumably reflecting increased lipid oxidation.
      CONCLUSIONS: Administration of GH in a therapeutic dose for 2 weeks, despite
      apparently normal daytime levels of major metabolic hormones, induces significant
      increases in circulating lipid fuel substrates, increased energy expenditure and
      lipid oxidation, together with insulin resistance. Such effects should be
      considered when applying GH treatment schedules clinically.

PMID- 8252749
TI  - Insulin-like growth factor-I blood levels in severely burned patients: effects of
      time post injury, age of patient and severity of burn.
AB  - OBJECTIVES: Insulin-like growth factor-I (IGF-I) is a polypeptide growth factor
      that stimulates protein synthesis. The aims of this study were to determine (1)
      the effect of a severe burn on blood IGF-I levels and (2) the variables
      controlling IGF-I level variations during recovery of these hypermetabolic
      patients. PATIENTS: Eleven patients, nine men and two women (age range 22-55
      years) were studied for 25 days following a severe burn (18-75% of total body
      surface area, mean 36%). Nitrogen balances were recorded daily and total IGF-I
      levels were measured every 3 days. MEASUREMENTS: IGF-I was extracted from serum
      using a validated formic acid-acetone methodology, then measured by a double
      antibody radioimmunoassay. IGF-I levels were compared to those of a reference
      healthy population. RESULTS: Within 24 hours following injury, IGF-I levels were
      low in all patients when compared to normal values for the same age range (mean
      +/- SEM of all patients, 131 +/- 26 micrograms/l). They remained low for the
      first week (days 4 and 7, 109 +/- 16 micrograms/l), then increased to reach
      normal values at the end of the study period (days 10-16, 144 +/- 19
      micrograms/l, P = 0.005 when compared to days 4-7; days 19-25, 206 +/- 30
      micrograms/l, P = 0.008 when compared to days 10-16). IGF-I levels were
      negatively correlated with age in the second phase of recovery only (days 10-16,
      r = -0.70, P < 0.05; days 19-25, r = -0.75, P < 0.01) and with severity of burn
      between days 19 and 25 (r = -0.62, P < 0.05). The presence of bronchial burn
      injury tended to lower IGF-I blood concentration (P = 0.08). Whereas IGF-I
      concentrations increased in the later phase of recovery, nitrogen balances did
      not. As a result, there was no significant correlation between these parameters.
      CONCLUSIONS: IGF-I levels followed a biphasic pattern in severely burned
      patients. They dropped dramatically in response to the traumatic shock, then
      increased during recovery. The degree of increase was dependent on the age of the
      patient and on the severity of the burn, but was not associated with an
      improvement in the nitrogen balance.

PMID- 8252750
TI  - Leucine metabolism in patients with Cushing's syndrome before and after
      successful treatment.
AB  - OBJECTIVE: Results from studies on the effect of glucocorticosteroids on protein
      turnover in both rat and man have been conflicting. The aim of this study was to
      investigate the primary cause of muscle wasting in patients with Cushing's
      syndrome. DESIGN: Studies of whole body 1(-14)C-leucine turnover in patients with
      Cushing's syndrome before and after successful treatment, and in control
      subjects. PATIENTS: Eleven patients with Cushing's syndrome before and after (n =
      5) treatment and 11 control subjects. MEASUREMENTS: Whole body 1(-14)C-leucine
      turnover to determine leucine metabolic clearance rate, leucine production rate,
      leucine oxidation rate and leucine incorporation into protein. RESULTS: Plasma
      leucine concentration (mean +/- SEM 100 +/- 6 mumol/l), leucine metabolic
      clearance rate (9.97 +/- 0.11 mumol/min/kg), leucine turnover (0.98 +/- 0.11
      mumol/min/kg) and leucine incorporation into protein (0.71 +/- 0.09 mumol/min/kg)
      were all significantly reduced in patients with Cushing's syndrome compared with
      control subjects (122 +/- 6 mumol/l, P < 0.05; 13.61 +/- 1.27 mumol/min/kg, P <
      0.05; 1.65 +/- 0.12 mumol/min/kg, P < 0.05; 1.46 +/- 0.10 mumol/min/kg, P <
      0.001, respectively). Leucine oxidation rate was similar in the patients with
      Cushing's syndrome and control subjects. When leucine metabolism was expressed in
      terms of lean body mass (LBM) in five patients with Cushing's syndrome and 11
      control subjects, leucine MCR, leucine turnover and leucine oxidation were not
      significantly different in the two groups. However, leucine incorporation into
      protein was significantly reduced (P < 0.001) in the patients with Cushing's
      syndrome (1.07 +/- 0.20 mumol/min/kg LBM) compared with control subjects (1.95 +/
      0.11 mumol/min/kg LBM). CONCLUSION: We conclude from these studies that the
      muscle wasting associated with Cushing's syndrome is primarily due to a reduction
      in protein synthesis.

PMID- 8252751
TI  - Abnormal twenty-four hour pattern of pulsatile luteinizing hormone secretion and
      the response to naloxone in women with hyperprolactinaemic amenorrhoea.
AB  - OBJECTIVE: Hyperprolactinaemic amenorrhoea is associated with disturbances of
      pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and
      the aim of this study was to investigate the 24-hour secretory pattern of
      gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of
      opioid blockade using naloxone infusion on LH secretory pattern was also studied.
      DESIGN: The secretory patterns of LH, FSH, PRL and their responses to naloxone
      infusion were studied by serial blood samples collected at 10-minute intervals
      for 24 hours. On the following day, naloxone was infused at a dose of 1.6 mg per
      hour for 4 hours. PATIENTS: Eight women with hyperprolactinaemic amenorrhoea, two
      women hyperprolactinaemic but with normal ovarian cycles, and nine control
      subjects in the early follicular phase of menstrual cycle. MEASUREMENTS:
      Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10
      minute intervals for 24 hours. In one woman, concentrations of urinary oestrone
      glucuronide were measured daily during treatment with pulsatile GnRH. RESULTS:
      The number of LH pulses per 24 hours was significantly fewer in women with
      hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with
      normal cycles or control subjects (mean +/- SEM 4.5 +/- 2.4 vs 13.5 +/- 2.5 vs
      17.3 +/- 0.8, P < 0.001). The magnitude of each episode of secretion was
      significantly higher in the hyperprolactinaemic amenorrhoeic women (P < 0.05) so
      the overall mean concentrations of LH throughout the 24-hour period was similar
      in the three groups (5.2 +/- 1.1, 4.8 +/- 0.8 and 5.2 +/- 0.4 U/l respectively).
      In women with hyperprolactinaemic amenorrhoea there was no significant change in
      the pattern of LH secretion during sleep in contrast to the control women in whom
      there was a slowing in the LH pulse frequency during the night. There was no
      significant change in the mean concentrations of LH, FSH and PRL during the
      naloxone infusion. There were also no significant changes in the LH pulse
      frequency in response to naloxone infusion when compared with an equivalent
      period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic
      woman, follicular development, ovulation and pregnancy were induced when
      gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a
      dose of 5 micrograms every 90 minutes. CONCLUSIONS: The suppression of normal
      ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a
      significant reduction in frequency of LH (GnRH) secretion which is not due to an
      increase in hypothalamic opioid activity. As normal ovarian cycles can occur or
      be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high
      level of prolactin by itself inhibits follicular development and ovulation.

PMID- 8252752
TI  - Growth hormone treatment affects plasma LH pulsatile release in women with
      secondary amenorrhoea.
AB  - OBJECTIVE: Since growth hormone (GH) is administered as a co-gonadotrophic factor
      in ovulation induction, this study aimed to assess the action of GH on the
      episodic pulsatile release of LH and FSH in amenorrhoeic patients. PATIENTS AND
      DESIGN: Nineteen patients affected by hypothalamic amenorrhoea were enrolled for
      this study: group A, 9 patients with normal gonadotrophins; group B, 10 patients
      with low gonadotrophins. Both groups were studied during GH infusion (0.015
      IU/min for 4 hours) and after 7 days of GH administration (0.1 IU/kg/day).
      Patients underwent a 4-hour pulsatility study, with blood sampling every 10
      minutes. A standard GnRH test (10 micrograms i.v. bolus) was performed
      immediately after the pulsatility evaluation. MEASUREMENTS: LH and FSH were
      assayed with an IFMA method; oestradiol and IGF-I were assayed by RIA and IRMA,
      respectively. PULSE DETECTION: Time series were analysed with Detect program.
      RESULTS: All patients showed similar LH and FSH pulsatile characteristics both
      under baseline conditions and during GH infusion. After 7 days of GH
      administration, episodic FSH release showed no change in either group. On the
      contrary, LH pulse frequency (mean +/- SE) significantly increased in group A
      (4.0 +/- 0.2 peaks/4h, P < 0.05), while pulse amplitude (baseline, 3.9 +/- 0.6
      IU/l; after 7 days, 2.9 +/- 0.3 IU/l, P < 0.05), and integrated LH plasma
      concentrations (baseline, 7.6 +/- 1.1 IU/l; after 7 days, 5 +/- 0.8 IU/l, P <
      0.05) were significantly decreased. No significant changes were observed for LH
      pulse frequency, amplitude or integrated LH plasma concentrations in
      hypogonadotrophinaemic patients (group B). Plasma oestradiol levels were
      significantly increased only in group A (baseline, 154.18 +/- 23.8 pmol/l; after
      7 days, 380.3 +/- 110.1 pmol/l, P < 0.05), while IGF-I levels were significantly
      increased in both groups after 7 days of GH administration (P < 0.05). No
      significant differences were observed in the gonadotrophin responses to GnRH test
      before and after GH administration. CONCLUSIONS: The present study showed that
      the administration of GH in amenorrhoeic patients determines the significant
      changes in episodic LH release in those subjects with normal LH plasma levels and
      suggests that the action of GH may be dependent upon the ovarian-pituitary
      feedback action.

PMID- 8252753
TI  - Necrosis of a phaeochromocytoma associated with spontaneous remission of diabetes
      and hypertension.
AB  - The diagnosis of phaeochromocytoma is sometimes difficult since its clinical
      presentation is quite variable. We report a 52-year-old woman who presented with
      acute diabetes mellitus and severe hypertension, which spontaneously disappeared.
      MIBG-scintigraphy and urine and plasma catecholamines were normal. At surgery, a
      largely necrotic phaeochromocytoma was found. Pathological examination
      demonstrated extensive avascular necrosis, which had occurred spontaneously
      without any major symptoms.

PMID- 8252754
TI  - Tissue-specific modulation of insulin receptor mRNA levels in a patient with a
      phaeochromocytoma.
AB  - We have observed that the expression of the insulin-receptor gene is regulated in
      a tissue-specific manner in a patient with a phaeochromocytoma. Our results
      indicate that insulin receptor mRNA levels are decreased in adipose tissue and
      increased in both liver and skeletal muscle as compared with the corresponding
      values in the same tissues of a control patient. These findings provide the first
      evidence that insulin receptor mRNA levels may be modulated in vivo by high
      levels of catecholamines.

PMID- 8252755
TI  - The hidden face of dermatology.

PMID- 8252756
TI  - Further experience of public education for the early diagnosis of malignant
      melanoma in Leicestershire.
AB  - Publicity campaigns alerting the public to the need for early attention to
      malignant melanoma (MM) were conducted in Leicestershire, England during the
      summers of 1987, 1988 and 1989. There was a marked, and statistically
      significant, rise in the number of referrals with good prognosis MMs in the
      period immediately after the first campaign. In the 2 subsequent years, despite
      further publicity campaigns, the number of MMs diagnosed per week remained lower
      than the postpublicity peak of 1986/87. The postpublicity rise was less marked in
      1987/88 and 1988/89. In the next year (1989/90), in which there was no publicity
      campaign, the total number of MMs seen was higher than in 1988/89. Numbers of MMs
      seen per week remained relatively steady throughout the year. There was again no
      publicity in 1990/91, and the total number of MMs diagnosed was about the same as
      in the previous year. There was a rise in the number of MMs seen per week in what
      would have been the postpublicity period of this year. The initial results would
      be consistent with the initial postpublicity rise in numbers of MMs seen being
      made up of lesions seen 'early', that is, in 1986/87 and 1987/88. Since these
      lesions were seen earlier than they would have been had there been no publicity,
      the number of MMs seen in 1988/89 was lower than it would otherwise have been and
      the publicity effort appeared to have less effect. By 1989/90 and 1990/91 this
      effect seems to have been wearing off. It may be that, at least in low MM
      incidence areas like the UK, it is better to pulse public education for the early
      diagnosis of melanoma rather than to use annual or continuous campaigns. However,
      longer-term experience, and the pooling of data between centres will be necessary
      to test this conclusion.

PMID- 8252757
TI  - Prevalence of skin and other cancers in patients with psoriasis.
AB  - The prevalence of skin and internal malignancies was estimated from the general
      practitioners' notes of 2247 patients with psoriasis and 4494 age- and sex
      matched controls. The prevalence of skin cancer in the psoriatics was 155% that
      of controls, but this was not significant at the 5% level. Subgroup analysis
      showed an increase in skin cancers in women (P < 0.05). There was no difference
      in the age of onset of skin cancers between psoriatics and controls and there was
      no evidence of a cumulative therapeutic risk. There was no difference in the
      prevalence of non-skin cancers between psoriatics and controls.

PMID- 8252758
TI  - Analyses of skin surface lipid in patients with microbially associated skin
      disease.
AB  - The composition of the total skin surface lipid, free fatty acids and fatty acid
      of triglyceride was used in discriminant analyses to classify patients with
      severe acne vulgaris (AV), pityriasis versicolor (PV), seborrhoeic dermatitis
      (SD) and atopic dermatitis (AD). It was not possible to discriminate between the
      PV and SD patients but all the lipid groups gave a satisfactory separation
      between AV, PV + SD and AD patients. A similar separation was obtained when the
      sex of the patient was studied but not when both sex and disease were taken into
      account. The results suggest that there are fundamental differences in the
      composition of skin lipid between patients with microbially associated diseases,
      but the precise role of the organisms has not been ascertained.

PMID- 8252759
TI  - Effect of a topical erythromycin-zinc formulation on sebum delivery. Evaluation
      by combined photometric-multi-step samplings with Sebutape.
AB  - Zinc displays 'in vitro' some antiandrogen activity through an inhibition of the
      5 alpha-reductase activity. The clinical relevance of this effect is unknown,
      particularly during zinc therapy of acne. As sebum production could be a
      pharmacological target, a sensitive method was used for measuring the rate of
      sebum delivery to the skin surface during treatment with a topical 4%
      erythromycin-1.2% zinc acetate formulation. A series of four successive 1-h
      samplings with Sebutape was taken to derive the rate of sebum output from the
      slope of the regression line given by cumulative data. As a control the classical
      photometric method was used. Such combined evaluation revealed a sebosuppressive
      effect for the topical zinc formulation tested.

PMID- 8252760
TI  - The Psoriasis Disability Index--further analyses.
AB  - Clinicians have become increasingly aware of the important effects of psoriasis
      on patients' quality of life. As a result, several measures of the disabilities
      and handicaps associated with psoriasis have been developed. The Psoriasis
      Disability Index (PDI) has been shown to be sensitive to changes in the extent of
      lesions and to co-vary with the Sickness Impact Profile, a more general measure
      of the effects of disease on quality of life. In this study, patients with
      psoriasis and patients with other skin diseases completed the PDI. Although most
      items on the PDI were specific to psoriasis, some items applied to patients with
      urticaria, eczema, melanomas and other skin diseases. A factor analysis of the
      items indicated that the PDI contained two subscales, one concerning most aspects
      of everyday activities, the other concerning specific public situations such as
      the use of communal facilities.

PMID- 8252761
TI  - Use of autografts for the treatment of leg ulcers in elderly patients.
AB  - Human keratinocytes obtained from seven elderly patients who had long-standing
      leg ulcers of venous or rheumatoid origin were grown into sheets for autografting
      on to their ulcers on at least one and, in some cases, two occasions. Following
      the application of the autografts on to the ulcers the appearance of the ulcer
      base improved with an increase in the vascularity of the granulation tissue and
      decrease in the amount of exudate. An 'edge effect' was also noted in five cases,
      with the previously indolent-looking edge of the ulcer appearing healthier and
      more active. However, over a 4-month follow-up period there was no complete re
      epithelialization in any of the ulcers despite these initial improvements.

PMID- 8252762
TI  - Successful differentiation of Spitz naevus from malignant melanoma by
      microfluorometric analysis of cellular DNA content.
AB  - Two cases of presumed Spitz naevus, whose diagnosis on clinical and histological
      grounds was uncertain, were examined for cellular DNA content using the technique
      of DAPI-DNA microfluorometry. They were compared with 20 cases, respectively, of
      clinically and histologically confirmed, Spitz naevus, malignant melanoma and
      acquired pigmented naevus. The two Spitz naevi showed a diploid pattern in a
      distribution histogram of cellular DNA content. The pattern was similar to that
      of confirmed Spitz naevi and of acquired pigmented naevi but different from the
      aneuploid pattern of malignant melanomas. DNA index values of the two cases were
      within the range of confirmed Spitz naevi and different from those of malignant
      melanomas. The DAPI-DNA microfluorometric method thus provided confirmatory
      evidence for the diagnosis of Spitz naevus. The method appears to reflect
      sensitively the biological behaviour of tumour cells, and is a useful aid to the
      diagnosis of uncertain Spitz naevi.

PMID- 8252763
TI  - Phototoxic eruptions due to doxycycline--a dose-related phenomenon.
AB  - The tetracycline group of antibiotics still remains the most successful oral
      treatment for acne. They are relatively free from side-effects apart from the
      occasional gastrointestinal upset or vaginal candidosis. Rarer side-effects
      include drug rashes, pigmentation with minocycline and a light-sensitive eruption
      with doxycycline. The incidence of light-sensitive rashes with doxycycline at a
      dose of 100 mg daily, is in the order of 3%. Acne does not always respond to
      conventional regimens of antibiotics and higher dosages may be required. We
      report a highly significant incidence of light-sensitive eruptions in patients
      receiving doxycycline at a daily dose of 150 mg or above.

PMID- 8252764
TI  - Comparison of toxicity tests on human skin and epidermoid (A431) cells using free
      fatty acids as test substances.
AB  - Several in-vivo methods can be used to determine the ability of chemical
      compounds to induce skin irritancy. In this study we estimated in vivo the
      capacity of several free fatty acids to induce skin irritancy and compared the
      results with those found in in vitro tests. Skin irritancy induced by free fatty
      acids (chain lengths: C6, C7, C9, C10, C11, C13 and C18) was evaluated in humans
      by means of laser-Doppler flowmetry (LDF) and visual scoring (VS). Both methods
      demonstrated that the toxic effect of free fatty acids determined by LDF and VS
      increased from C6 through C11 and decreased again for C13 and C18. The cytotoxic
      effect of these free fatty acids on cells was measured in vitro by incubation of
      human epidermoid cells (A431) with these compounds. It was determined by
      measuring: (a) the number of dead cells by inclusion of Trypan blue (TB); and (b)
      the number of living cells by mitochondrial metabolism of 3-[4,5-dimethylthiazole
      2-yl]-2,5 diphenyltetrazolium bromide (MTT). The LD-50 concentrations decreased
      from C6 through C11 in both in-vitro assays. The results of the in-vitro assays
      for C13 and C18 both demonstrated a discrepancy. The cytotoxic effect of the free
      fatty acids expressed as LD-50 values, determined after 20 min with the TB assay,
      was seen at higher concentrations than after incubation for 18 h (MTT assay).
      From the results it was concluded that C13 in particular affected skin blood
      flow. We also determined correlation coefficients between the in-vivo and in
      vitro methods. When C13 is excluded these coefficients ranged from -0.77 to 
      0.92.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252765
TI  - Atypical cutaneous lesions of Lyme disease.
AB  - In 30 patients with Lyme disease, the lesions of erythema chronicum migrans were
      absent or atypical. Thirty biopsy specimens were obtained from cutaneous lesions
      of these patients. The predominant histological finding was a superficial dermal
      and deep perivascular and interstitial infiltrate composed mostly of lymphocytes
      but containing a few eosinophils and plasma cells. In serial sections with a
      silver stain, a few Borrelia burgdorferi were found in the biopsy specimens from
      cutaneous lesions in five patients. Thus, there is evidence that the typical
      lesions of erythema chronicum migrans of the classical Lyme disease do not
      develop while Borrelia burgdorferi survive and persist in cutaneous lesions.

PMID- 8252766
TI  - Black heel with atypical melanocytic hyperplasia.
AB  - Two cases with a black pigmented patch on the heel are reported. Biopsy specimens
      showed that atypical melanocytic hyperplasia was confined to the epidermis
      despite the lesion being present for a long time. The diagnosis of atypical
      melanocytic hyperplasia should be considered in the differential diagnosis of the
      black heel.

PMID- 8252767
TI  - Malignant atrophic papulosis. A report of two cases with altered fibrinolysis and
      platelet function.
AB  - Malignant atrophic papulosis is a systemic vaso-occlusive disorder characterized
      by typical skin lesions. We report two new cases with impairment of blood
      fibrinolytic activity and alterations in platelet function. The first case showed
      an increase in plasminogen activator inhibitor-1 (PAI-1) activity, and the second
      case had a decrease in platelet aggregation induced by adenosine diphosphate and
      adrenaline but normal with collagen. The impairment of blood fibrinolytic
      activity and platelet aggregation may have pathogenic and therapeutic
      implications in malignant atrophic papulosis.

PMID- 8252768
TI  - Bazex's syndrome (acrokeratosis paraneoplastica)--first case report of
      association with a bladder carcinoma.
AB  - Bazex's acrokeratosis paraneoplastica is a clinically well-defined entity
      consisting of a distal erythemato-squamous eruption and nail dystrophy. It is
      always associated with neoplasia, mainly squamous carcinomas of the upper
      digestive and respiratory tracts; therefore, Bazek's acrokeratosis is considered
      to be a specific marker of internal malignancy. Two new cases of this syndrome
      are reported. The first was in a 41-year-old man with a squamous cell carcinoma
      of the oesophagus, the second in a 73-year-old man who presented with a
      transitional cell bladder carcinoma, an association not previously reported.

PMID- 8252769
TI  - Pregnancy-induced chilblain lupus erythematosus.
AB  - A case of chilblain lupus erythematosus during pregnancy is described in a 28
      year-old woman. Symptoms and signs were present by 8 weeks of her first pregnancy
      and had resolved by 10 days after delivery. The condition is discussed with
      particular emphasis on the relationship with pregnancy.

PMID- 8252770
TI  - Generalized melanosis with malignant melanoma metastasizing to skin--a
      pathological study with S-100 protein and HMB-45.
AB  - A patient with primary malignant melanoma localized to the right gluteal region
      is described. Four years later and after intercurrent influenza, disseminated
      metastases of malignant melanoma to the skin occurred. After a further 6 months
      melanodermia developed and lasted until the death of the patient (6 months
      later). Autopsy revealed melanosis of the visceral organs. Histology taken from
      internal organs using S-100 protein and HMB-45 melanoma methods confirmed
      metastases of malignant melanoma to the skin, oral cavity, palatal tonsils, nasal
      and nasopharyngeal mucosae, lungs, myocardium and brain. The authors discuss the
      mechanism of melanosis--a rare sign in patients with metastasizing malignant
      melanoma.

PMID- 8252771
TI  - Cutaneous granuloma with ataxia telangiectasia--a case report and review of
      literature.
AB  - A patient is reported who had ataxia telangiectasia with multiple cutaneous
      lesions mainly on the limbs, which showed atrophy and scarring. Histopathology of
      these skin lesions showed tuberculoid granulomas without frank collagen
      necrobiosis in the dermis. Chromosomal analysis revealed a translocation between
      7 and 14 as well as deletion of chromosomes 4 and 6.

PMID- 8252772
TI  - Multiple xanthogranulomas in an adult.
AB  - Xanthogranulomas develop in adults as well as in children; however, adult cases
      with multiple lesions are very rare. We report an adult who developed both
      multiple cutaneous lesions on the face and trunk and lesions on the conjunctiva,
      oral mucosa and genitalia. We believe that this is the first such case described.

PMID- 8252773
TI  - Suprabasal acantholysis--an unusual feature of necrolytic migratory erythema.
AB  - A 67-year-old man with diabetes, weight loss and anaemia initially presented with
      a widespread scaling erythematous rash; a skin biopsy demonstrated marked
      suprabasal acantholysis. A subsequent biopsy showed localized upper epidermal
      necrolysis and the diagnosis of glucagonoma syndrome was later confirmed.
      Glucagonoma syndrome should be considered in patients with diabetes, weight loss
      and anaemia who present with a scaling rash, the histology of which shows
      suprabasal acantholysis. The extent of any upper epidermal necrolysis may be be
      very limited.

PMID- 8252774
TI  - Unilateral localized idiopathic lipoatrophy.
AB  - An adult female is described in whom an area of lipoatrophy spontaneously
      appeared over the right side of the abdomen and chest. Idiopathic lipoatrophy
      affecting the trunk is rare and mainly described in Japanese children. We
      describe the condition occurring in an adult British female.

PMID- 8252775
TI  - A case of malignant haemangioendothelioma treated with recombinant interleukin-2.
AB  - A case of malignant haemangioendothelioma of the scalp in an 82-year-old female
      treated with intralesional, intra-arterial and intravenous recombinant
      interleukin-2 (rIL-2) is reported. The scalp lesions disappeared after injection
      of 35,350,000 Japan reference units of rIL-2 and excision of the residual tumour.
      Immunohistochemical characterization of the cells infiltrating the lesion after
      rIL-2 administration revealed 30-40% CD4+ and CD8+ T lymphocytes, 20-30%
      macrophages and 5-10% natural killer cells. These findings are similar to those
      in other human cancers. Almost all of the cells in the intersticies of the lesion
      after rIL-2 injection expressed leucocyte function-associated antigen-1, and some
      of the tumour cells and the infiltrating cells around them expressed
      intercellular adhesion molecule-1. HLA-DR-positive cells markedly increased in
      number after rIL-2 administration. This report suggests that rIL-2 administration
      is the most effective therapy for malignant haemangioendothelioma.

PMID- 8252776
TI  - Lupus pernio following facial trauma.
AB  - Cutaneous sarcoidosis may occur at sites of trauma. Two patients are reported in
      whom lupus pernio developed in the area of facial fractures. Injury may be a
      factor in the site of development of lupus pernio in some individuals and may
      have medico-legal implications. Cutaneous sarcoidosis is known to occur at the
      sites of scars and trauma but lupus pernio has not been widely recognized to show
      this phenomenon. We report two patients in whom lupus pernio developed at the
      site of facial trauma.

PMID- 8252777
TI  - Pachyonychia congenita with late onset of nail dystrophy--a new clinical entity?
AB  - Pachyonychia congenita syndrome (PCS) is a genetic disease with an autosomal
      dominant mode of transmission in which the main sign, pachyonychia, usually
      arises at birth or in childhood together with other disorders of keratinization.
      A 28-year-old woman developed subungual hyperkeratosis of all toe-nails and thumb
      nails associated with pain on pressure and walking. She had a scrotal tongue with
      leucokeratotic areas, blister formation, plantar hyperkeratosis, palmoplantar
      hyperhidrosis and dental cavities since childhood. The present case, interpreted
      as PCS of late onset, could be a clinical variant of the Jadassohn-Lewandowsky
      syndrome with the late onset of pachyonychia or else an additional form of PCS
      due to the expression of a new and different allele.

PMID- 8252778
TI  - Tinea nigra palmaris.
AB  - Tinea nigra is a clinically distinctive superficial mycosis of the palms, and
      occasionally the soles, caused by Phaeoannellomyces werneckii. A patient,
      resident in the United Kingdom, is described who acquired the infection in
      Thailand. The condition cleared after treatment with topical miconazole cream 2%.

PMID- 8252779
TI  - Bullous pemphigoid in infancy--a case report including new immunoblotting
      observations.
AB  - A 1-year-old boy developed bullous pemphigoid. Immunoblotting, which has not been
      previously reported in childhood pemphigoid, showed the serum reacted to a 190
      kDa band only. Bullous pemphigoid is rare in infancy and childhood with only 40
      cases previously reported. A brief review of the literature is given and
      treatment of childhood bullous pemphigoid is discussed.

PMID- 8252780
TI  - Improving the risk-benefit ratio of cyclosporin.

PMID- 8252781
TI  - Pulmonary hypertension in systemic lupus erythematosus--treatment with high dose
      nifedipine therapy?

PMID- 8252782
TI  - Remission of Langerhans cell histiocytosis with thalidomide treatment.

PMID- 8252783
TI  - Platelet activating factor--a mediator of inflammation in the skin--medical
      implications.

PMID- 8252784
TI  - Atopic eczema in a multiracial country (Malaysia).
AB  - A total of 14,342 patients with skin diseases who had attended either the
      National University of Malaysia skin clinic or a private dermatological office
      were analysed. Five hundred and thirty-four cases (3.7%) had atopic eczema, the
      prevalence being highest among the Malays (4.3%). The prevalence of atopic eczema
      among clinic attenders is lower in all three major Malaysian races when compared
      with studies from England.

PMID- 8252785
TI  - Treatment of epidermal cysts with Solcoderm (a copper ion and acid solution).
AB  - The treatment of epidermal cysts has often posed a problem for dermatologists.
      Although surgical excision has been adopted as the method of choice for the
      removal of these lesions, complications of surgery and recurrences have warranted
      the search for alternate therapeutic modalities. Use of a recently introduced
      compound, Solcoderm, is reported in the treatment of 116 epidermal cysts in 85
      patients over a 2-year period. The satisfactory cosmetic results observed, low
      incidence of recurrence, low cost and ease of administration, make this drug a
      viable alternative in the management of epidermal cysts, particularly in those
      cases where surgery should be avoided.

PMID- 8252786
TI  - Occlusion enhances the efficacy of topical calcipotriol in the treatment of
      psoriasis vulgaris.
AB  - Forty-eight patients with symmetrical chronic plaque psoriasis affecting the
      limbs were recruited for a single-blind right/left within patient study to assess
      the effect of combining occlusion with topical calcipotriol. Subjects were
      randomized into two groups. Sites of similar severity on opposing limbs were
      selected as target areas. The first (group A) treated one side with calcipotriol
      alone and the opposite side with calcipotriol plus occlusion. The second (group
      B) treated one side with placebo plus occlusion and the opposite side with
      calcipotriol plus occlusion. In group A the mean improvements were 40% (P <
      0.001) for calcipotriol alone and 61% (P < 0.001) for calcipotriol plus
      occlusion. In group B, occlusion plus calcipotriol resulted in a mean 62%
      improvement (P < 0.001) while occlusion plus placebo produced no significant
      change. The combination of calcipotriol plus occlusion was significantly better
      than calcipotriol alone (P < 0.005). The results indicate that occlusion improves
      the response to calcipotriol by enhancing its penetration. Indices of calcium
      metabolism remained unchanged throughout the study.

PMID- 8252787
TI  - Skin tuberculosis as seen at Ga-Rankuwa Hospital.
AB  - The experience with cutaneous tuberculosis at Ga-Rankuwa Hospital is reviewed. A
      total of 92 cases of skin tuberculosis was seen over the past 12 years. All
      recognized forms of cutaneous tuberculosis were encountered, plus some forms
      which were difficult to classify. Lupus vulgaris was the most common true
      infection and papulonecrotic tuberculid the most common tuberculid. The
      classification and pathogenetic mechanisms are briefly discussed.

PMID- 8252788
TI  - What do members of the National Eczema Society really want?
AB  - In order to assess the impact of eczema on the lives of affected individuals a
      postal questionnaire was sent to all members of the National Eczema Society
      (NES). The survey also sought to ascertain their expectations of their initial
      consultation with general practitioners and hospital doctors; to assess their
      satisfaction with these consultations; to obtain their views on the treatment
      prescribed, and their reasons for joining the NES. Information on 1972 adults
      (614 male, 1358 female) and from 1944 parents of affected children was received,
      representing an overall response rate of 29%. The work of 1061 (54%) adults, and
      the choice of career of 391 (20%) had been affected. Eczema affected the ability
      to perform domestic duties in 1128 (83%) women compared with 439 (71%) men.
      Social and leisure activities were affected in 1269 (64%) of adults. The
      development of personal relationships had been impaired in 273 (14%), and the sex
      lives of 373 (19%) had been affected. In children sleep (60%) was the most
      commonly affected activity. The expectations of the initial consultation with
      their general practitioner of 659 (17%) had not at all been met, of 2528 (65%)
      partly met, and of only 483 (12%) completely met; 2638 patients had seen a
      hospital specialist. The expectations of 478 (18%) had not at all been met, of
      1164 (62%) partly met, and of only 512 (19%) completely met. Forty-four per cent
      (1713) were either 'extremely satisfied' or 'satisfied' with the treatments they
      had been given, 1529 (40%) were 'neutral', 480 (12%) were dissatisfied, and 103
      (2.6%) were extremely dissatisfied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252789
TI  - Chloracne--study of an outbreak with new clinical observations.
AB  - A recent outbreak of chloracne in 17 workers is reported at a plant manufacturing
      dichloroaniline derivatives. Comedones developed 6-12 weeks after accidental
      exposure to the chloracnegenic contaminants and were present in every case.
      Cutaneous xerosis and a folliculitis, previously only rarely described as
      manifestations of chloracne, were noted in half the patients. The pathogenesis of
      these lesions is uncertain but may involve a disorder of keratinization.

PMID- 8252790
TI  - Cutaneous B-cell lymphoma--a clinical, pathological and immunohistochemical
      study.
AB  - Eleven cases of cutaneous B-cell lymphoma (CBCL) were studied. The ages at
      presentation ranged from 34 to 79 years (mean = 59.9 years). Six patients were
      female and five male. Five of the 11 patients had a solitary tumour and the other
      six had multiple tumours at initial presentation. According to Burg's
      classification, six cases were at stage I, two stage II, two stage III and one
      was at stage IV at initial presentation. Abnormalities in laboratory data were
      rare, except for serum lactic dehydrogenase values. Epidermotropism was not
      detected, and the area mainly affected by neoplastic cells was the reticular
      dermis (seven cases) and subcutis (four cases). Biopsy specimens from the
      patients analysed by immunohistochemical techniques on paraffin or cryostat
      sections showed CD20 and/or CD22 positivity. Biopsy specimens from two patients
      which showed CD10 positivity were diffuse large cell types by the working
      formulation and presented as pre-B-cell lymphoma. At least two groups of CBCL
      were demonstrable on the basis of prognosis. One was a benign low-grade lymphoma
      presenting with solitary tumours, mature B-cell markers and intermediate-grade
      pathology, and the other was a high-grade lymphoma with multiple tumours, pre-B
      cell or mature B-cell markers and a poor prognosis.

PMID- 8252792
TI  - Carbamazepine-induced anticonvulsant hypersensitivity syndrome--pathogenic and
      diagnostic considerations.
AB  - Two epileptic patients developed an infectious mononucleosis-like illness which
      subsequently proved to be a carbamazepine-induced anticonvulsant hypersensitivity
      syndrome. Patch testing to carbamazepine 3 years later was positive in the one
      patient tested and negative in normal controls. The second patient died a few
      weeks after the illness, secondary to long-standing cardiac disease without
      having undergone patch testing. A skin biopsy was, however, consistent with an
      immune complex mediated drug reaction. Patch testing for systemically
      administered drugs is generally believed to be of little value in diagnosing drug
      allergies. However, we reinforce a previous suggestion that this investigation
      may be helpful in some cases of anticonvulsant hypersensitivity syndrome caused
      by carbamazepine. The pathogenic role of type 3 and 4 hypersensitivity is also
      discussed.

PMID- 8252791
TI  - Serious group A streptococcal infections complicating cryotherapy to lip
      haemangiomas.
AB  - Cryotherapy is a safe and effective way of treating haemangiomas of the oval
      cavity and lips without complications in adults in a reported series. Two cases
      of serious group A streptococcal infection after cryotherapy in two children are
      reported. In conclusion it is likely that these children were undiagnosed
      carriers for the organism. Pre-operative nasopharyngeal swabs would have
      identified this and prevented the complications which occurred.

PMID- 8252793
TI  - Necrobiosis lipoidica--involvement of atypical sites.
AB  - Necrobiosis lipoidica (NL) has distinctive clinical and histological appearances.
      The legs are the commonest site of involvement, and 85% of cases involve the legs
      exclusively. We describe a patient in whom NL did not involve the legs, but was
      found to occur on unusual areas: the back and nipple. This is possibly the first
      report of NL affecting the nipple.

PMID- 8252794
TI  - Pyoderma gangrenosum--a complication of chronic venous leg ulceration?
AB  - Three patients whose chronic venous leg ulcers were complicated by pyoderma
      gangrenosum are reported. Illnesses which may have predisposed to the development
      of pyoderma gangrenosum included Crohn's colitis, rheumatoid arthritis and small
      bowel perforation. Pyoderma gangrenosum should be suspected in susceptible
      patients whose venous leg ulcers undergo inexplicable and painful deterioration.

PMID- 8252795
TI  - Epidermolysis bullosa acquisita--a case with upper airways obstruction requiring
      tracheostomy and responding to cyclosporin.
AB  - The case is reported of a 56-year-old man with epidermolysis bullosa acquisita
      (EBA) who developed such severe involvement of the upper respiratory tract that a
      tracheostomy had to be performed. Control of his disease was ultimately obtained
      with cyclosporin and the use of this drug in EBA is reviewed.

PMID- 8252796
TI  - Lichen planus pemphigoides in a child--immunopathological findings.
AB  - Lichen planus pemphigoides is a rare immuno-bullous disorder which usually
      affects adults. It is extremely uncommon in children. Previous cases have been
      described in a 10-year-old girl and in two 16-year-old adolescents. A case of
      lichen planus pemphigoides in an 11-year-old Afro-Caribbean boy is reported and
      the immunopathological findings are discussed.

PMID- 8252797
TI  - Cardiac and systemic complications in multicentric reticulohistiocytosis.
AB  - A 75-year-old man with a short history of cutaneous lesions of multicentric
      reticulohistiocytosis, preceded by a few months of a symmetrical polyarthritis is
      described. Within 5 months of onset of symptoms, he developed congestive cardiac
      failure secondary to pericardial involvement by the disease and succumbed despite
      therapy with cyclophosphamide and methylprednisolone. Post-mortem revealed the
      true extent of the disease, with nodules seen in the epiglottis and aryepiglottic
      folds, duodenal mesentery, pleura, pericardium and myocardium. Although the
      hallmarks of the disease are the papulonodular skin lesions, together with a
      severe, sometimes mutilating polyarthropathy, its widespread systemic nature is
      not often appreciated. We review five other cases in the literature with
      pericardial involvement and discuss aids to earlier diagnosis by synovial fluid
      cytology; gallium scanning is discussed as a potentially useful means of
      detecting the extent of systemic involvement in multicentric
      reticulohistiocytosis.

PMID- 8252798
TI  - Disseminated cutaneous granulomatous eruptions associated with myelodysplastic
      syndrome and acute myeloid leukaemia.
AB  - Two elderly male patients presented with similar, widespread, papular,
      granulomatous eruptions and developed myelodysplastic syndromes. The first showed
      histological features of diffuse granuloma annulare and had mild
      hypergammaglobulinaemia, slightly abnormal liver function and a
      leucoerythroblastic anaemia. He developed acute myeloid leukaemia (AML) secondary
      to a background myelodysplastic syndrome and was treated with combination
      chemotherapy during which his eruption settled; his AML and his skin are in
      remission 1 year later. The second developed a myelodysplastic syndrome and a
      similar rash with histological features of papular cutaneous sarcoidosis but no
      systemic abnormalities apart from mild hypergammaglobulinaemia, cutaneous anergy
      to multiple recall antigens and activation of circulating monocytes. He has
      remained well but his rash and myelodysplastic syndrome have persisted. These
      cases are interesting because of the striking similarity of their granulomatous
      eruptions and their associated haematological abnormalities. Patients with such
      disseminated, granulomatous cutaneous infiltrations should be investigated to
      exclude associated haematological abnormalities if there is any abnormality of
      their peripheral blood picture.

PMID- 8252799
TI  - Heymann nephritis revisited--new insights into the pathogenesis of experimental
      membranous glomerulonephritis.

PMID- 8252800
TI  - Metabolic fate of monovalent and multivalent antibodies of Heymann nephritis
      following formation of surface immune complexes on glomerular epithelial cells.
AB  - Heymann nephritis of the rat has several similarities to human idiopathic
      membranous glomerulo-nephropathy, and therefore serves as an animal model for
      study of the human disease. The disease process in the rat is initiated by
      autoantibodies forming in situ immune deposits on the surface of the glomerular
      epithelial cell in the lamina rara externa region of the glomerular basement
      membrane. It is now understood that multispecific antibodies (like anti-gp600)
      form the nephritogenic deposits which cause proteinuria, while MoAb (like anti
      gp330, anti-90 kD and anti-gp70) form only transient deposits which do not give
      rise to proteinuria. The reasons for differences between pathologic effects of
      mono- and multispecific antibodies are not known. Following characterization of
      putative antigens of Heymann nephritis by immunofluorescence, immunogold and
      immunoblot techniques, we have investigated the metabolic handling of a
      multispecific (anti-600), monospecific antibody (anti-gp70) and a MoAb (anti
      gp330) by the cultured glomerular epithelial cell to gain an insight into the
      mechanism of nephritogenicity of multispecific antibody. Anti-gp600 reacted to
      multiple antigens in the 330-kD and 70-kD regions; anti-gp70 reacted to only the
      70-kD region. Ultrastructurally, all three types of antigens were present on the
      plasma membrane, concentrated in the microvillar region. The cells were incubated
      with the antibodies, and clearance of the antibodies from the cells was
      evaluated. Following binding, all three antibodies were internalized by the
      cells. However, it was found that monoclonal anti-gp330 MoAb was cleared most
      rapidly from the cell (t1/2 5 min), followed by anti-gp70 (t1/2 30 min). Anti
      gp600 was cleared at four times slower rate than anti-gp70 (t1/2 2h) by the cell.
      While anti-gp330 MoAb and monospecific anti-gp70 antibody were expelled from the
      cell in 25-32% digested form, the multispecific anti-gp600 was digested to the
      extent of only 5-8%. No immune complexes were detected in the medium with any of
      the three antibodies. The shed label was in intact IgG form. It is concluded that
      multispecific antibodies of Heymann nephritis are nephritogenic because of their
      slower clearance and digestion and therefore, higher accretion rate on the
      surface of the glomerular epithelial cell. The differential handling of the
      antibodies by the glomerular epithelial cell offers an explanation for the in
      vivo differences in the nephritogenicity of these antibodies observed earlier.

PMID- 8252801
TI  - Partial prevention of active Heymann nephritis by 1 alpha, 25 dihydroxyvitamin
      D3.
AB  - The hormone 1 alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3) has potent
      immunosuppressive effects in vitro. Recent publications also described a
      protective effect of the hormone in various animal models of immune-mediated
      diseases. To test its in vivo activity we induced active Heymann nephritis in
      Lewis rats that were either untreated or treated with 1,25(OH)2D3 or its
      synthetic 20-epi analogue, KH1060. Treatment with cyclosporine A (CsA) was used
      as an immunosuppressive control. In this nephrotic model the administration of
      1,25(OH)2D3 (0.5 microgram/kg body weight) given on alternate days during the
      first 13 days after active immunization significantly reduced the proteinuria as
      measured by weeks 7-9. This reduction was comparable to the reduction observed in
      rats treated with CsA (20 mg/kg) on alternate days. A second series of
      experiments with 1,25(OH)2D3 confirmed these findings. The level of
      autoantibodies was found to be significantly suppressed during the treatment time
      in the CsA (20 mg/kg) group, whereas the limit of significance (P = 0.06) was
      reached in the 1,25(OH)2D3 (0.5 microgram/kg) group. The size of the immune
      deposits also was found to be substantially smaller in the groups that developed
      less proteinuria. The administration of 1,25(OH)2D3 transiently increased the
      mean serum calcium concentration with 2.5 mg/dl above the pretreatment values,
      and the urinary calcium excretion by a factor of 3-5 during the short treatment
      time. Treatment with the analogue KH1060 did not reduce the proteinuria
      significantly. Our experiments add evidence to the hypothesis that 1,25(OH)2D3 in
      pharmacological doses has immunosuppressive potency.

PMID- 8252802
TI  - Increased proportion of responders to a murine anti-CD3 monoclonal antibody of
      the IgG1 class in patients with systemic lupus erythematosus (SLE).
AB  - A group of Venezuelan patients with SLE showed an increased proportion of
      responders to Leu-4, an anti-CD3 MoAb of the IgG1 class, compared with ethnically
      matched non-SLE patients and healthy controls. The rate of proliferative
      responses or IL-2 production induced by MoAb Leu-4, and the helper effect of
      macrophages from Leu-4 responders on T cells from a third-party donor were
      comparable in patients and controls. No significant differences in the binding of
      murine IgG1 molecules by macrophages from SLE patients and controls were
      observed. The proportion of monocytes/macrophages expressing Fc gamma RI was
      significantly higher in SLE patients. However, the expression of FcRII, the type
      capable of supporting Leu-4-mediated responses, and of Fc gamma RIII was
      comparable in monocytes from SLE patients and controls. Our results suggest that
      Venezuelan patients with SLE may have a genetic predisposition for the expression
      of the phenotypic variant of Fc gamma RII capable of binding murine IgG1
      molecules.

PMID- 8252803
TI  - A calreticulin-like protein co-purifies with a '60 kD' component of Ro/SSA, but
      is not recognized by antibodies in Sjogren's syndrome sera.
AB  - In this study, we used human tonsils for the isolation of the 60 kD component of
      the Ro/SSA autoantigen, following the method described by Wu et al. (J Immunol
      Methods 1989; 121:219-24). Western blot analyses were carried out using Ro/SSA
      reactive human Sjogren's syndrome sera, to follow the autoantigen through the
      purification procedure. A 60 kD Ro/SSA component was eluted as a broad peak from
      a Mono Q column. Within this peak, a much more abundant protein, co-migrating
      with the Ro/SSA component on SDS-PAGE, was also eluted. The more abundant protein
      was further purified on a Superose 12 column and its N-terminal sequence was
      shown to be identical to that of human calreticulin. The 60 kD Ro/SSA autoantigen
      was also further purified on the Superose 12 column and was eluted as an
      asymmetric peak, with the majority being eluted at a position corresponding to 60
      kD, whereas the calreticulin-like protein was eluted from the same column as an
      apparent dimer of approximately 120 kD. A panel of five Ro/SSA-reactive human
      sera reacted with the purified Ro/SSA antigen, but not with the calreticulin-like
      protein. Therefore, it is clear that the calreticulin-like protein is not a Ro
      autoantigen and is distinct from the 60 kD Ro/SSA antigen. As the calreticulin
      like protein is a much more abundant protein than the 60 kD Ro/SSA component, its
      co-purification with the autoantigen on ion-exchange and its close migration with
      the autoantigen on SDS-PAGE may explain why peptide sequences for human
      calreticulin were derived from apparent 60 kD Ro/SSA antigen preparations.

PMID- 8252805
TI  - Glycation increases the vascular clearance rate of IgG in mice.
AB  - As elevated levels of glycated IgG have been detected in the plasma of diabetics
      we have investigated whether glycation of IgG affects its vascular clearance
      rate, using a mouse model system. Polyclonal mouse IgG was aseptically incubated
      for 14-19 days with 0.5 M glucose in 0.1 M phosphate buffer (pH 7.4) at 37
      degrees C. As control, IgG was incubated under identical conditions but with no
      added glucose. After incubation, both forms were labelled with 125I and injected
      intravenously into BALB/c mice. The rate of vascular clearance of the glycated
      IgG was found to be significantly higher than the control IgG in the periods 5-24
      h (P < 0.001, n = 6) and 24-48 h (P < 0.01, n = 6) after injection. After 2-3
      days the mice were killed and the major organs were harvested. With glycated IgG
      there was a significant increase in the 125I accumulated in the kidney (P <
      0.02). In later experiments, dual labelling with 131I and 125I allowed mixtures
      of glycated and unglycated IgG to be injected into the same mouse so that the
      vascular clearance of both forms of IgG could be followed simultaneously. These
      experiments confirmed that glycation of the IgG significantly increases its
      vascular clearance rate.

PMID- 8252804
TI  - The putative oncoprotein DEK, part of a chimera protein associated with acute
      myeloid leukaemia, is an autoantigen in juvenile rheumatoid arthritis.
AB  - The 45-kD autoantigen associated with juvenile rheumatoid arthritis (JRA) has
      been isolated from HeLa cell nuclei and purified about 2500-fold to near
      homogeneity in a five-step chromatographic procedure. Purification of the antigen
      was monitored by immunoblot assays using a nearly monospecific anti-45-kD serum
      from a child with JRA. Tryptic peptide mapping and partial amino acid sequencing
      of the purified 45-kD antigen demonstrated its identity with the DEK protein. DEK
      is a 43-kD protein of unknown function expressed by the putative oncogene dek
      located on chromosome 6. As a result of a (6;9) translocation offociated with a
      rare subtype of acute myeloid leukaemia a chimeric protein containing most of DEK
      amino acids at the N-terminus is found in leukaemic cells (von Linden et al., Mol
      Cell Biol. 1992; 12: 1687-97). The 43-kD DEK was detected by immunoblotting with
      serum from a patient with JRA in a variety of rat tissues, and was most abundant
      in the spleen and in bone marrow.

PMID- 8252806
TI  - Adjuvant arthritis is associated with changes in the glycosylation of serum IgG1
      and IgG2b.
AB  - The increased amounts of agalactosyl IgG (N-linked oligosaccharides terminating
      with N-acetylglucosamine (GlcNAc) in the serum of patients with rheumatoid
      arthritis (RA) and other chronic inflammatory diseases have suggested that
      agalactosyl IgG may be involved in the pathogenesis of RA. We have now evaluated
      the incidence of agalactosyl IgG in the Lewis rat during the course of adjuvant
      arthritis (AA). The modification in glycosylation of IgG was measured by means of
      polyclonal and monoclonal anti GlcNAc antibodies as well as by the lectin
      concanavalin A (Con A). The results show that Lewis rats undergo a change in
      serum IgG glycosylation during the course of AA. As in human RA patients, rats
      with AA lack terminal galactose on IgG heavy chain oligosaccharides, and the
      terminal GlcNAc or mannose residues are thus exposed. The degree of agalactosyl
      IgG was positively correlated with the incidence of disease, peaked 20 days after
      disease induction, and the IgG gradually reverted to the fully glycosylated form
      thereafter. The post-arthritic glycosylation profile was very similar to that
      characteristic of the naive animal. Purified IgG was shown to contain two IgG
      subclasses, IgG1 and IgG2b, which underwent changes in glycosylation. Western
      blot analysis revealed that IgG1 expressed a higher degree of terminal mannose,
      whereas IgG2b expressed a higher degree of terminal GlcNAc. These findings raise
      the question of the possible involvement of agalactosyl IgG in immune complex
      mediated inflammation.

PMID- 8252807
TI  - Genes on the X chromosome affect development of collagen-induced arthritis in
      mice.
AB  - Susceptibility to collagen-induced arthritis (CIA) in mice is associated with a
      class II gene in MHC (Aq) but also with unknown genes outside MHC. Investigated
      here is the influence of genes on the X chromosome as well as the role of the X
      linked immunodeficiency (xid) mutation. Reciprocal male F1 hybrids, bred to be
      heterozygous or homozygous for Aq, showed a genetic influence in their
      susceptibility to develop CIA. Crosses were made between B10.G, B10.Q, DBA/1,
      SWR/J, C3H.Q and CBA/Ca, and all F1 mice were castrated to avoid sex hormone
      modulation of the susceptibility. A differential timing of arthritis onset and
      severity were seen in the reciprocal F1 males. An exception was the reciprocal F1
      male offspring from SWR/J and DBA/1 crosses which differed only in disease
      severity late in the course of the disease. The female F1 crosses did not show
      the same pattern of differential susceptibility to CIA as the F1 males. To
      exclude the possible influence of the Y chromosome, F1 males of reciprocal
      crosses were back-crossed to the parental strains creating offspring with equal X
      chromosomes but divergent Y chromosomes. No difference in development of
      arthritis was observed in these. The influence of the xid mutation was
      investigated next. The xid loci from the CBA/N mouse was bred into DBA/1 strain
      which is highly susceptible to CIA. The resulting congenic DBA/1-xid strain was
      resistant to induction of CIA and did not develop an antibody response to type II
      collagen. We conclude that polymorphic genes on the X chromosome modulate
      susceptibility to CIA. The results from the experiments with mice carrying xid
      mutations confirm that such immune modulating genes exist on the sex chromosomes.

PMID- 8252809
TI  - The gamma delta T cell repertoire in Graves' disease and multinodular goitre.
AB  - gamma delta T cells are a subset of T cells with unknown function, and
      restriction of the gamma delta T cell receptor (TCR) repertoire has been
      described in rheumatoid arthritis and multiple sclerosis. Elevated numbers of
      gamma delta T cells have been reported in the peripheral blood and thyroids of
      patients with Graves' disease. We have carried out flow cytometric analysis on
      peripheral blood mononuclear cells (PBMC) and intrathyroidal lymphocytes (ITL)
      from 12 patients with Graves' disease and nine patients with multinodular goitre
      (MNG), a thyroid disease of unknown etiology. There was no significant difference
      between the proportion of gamma delta T cells in the PBMC of Graves' and MNG
      patients, nor between the PBMC and ITL populations in either patient group. We
      have also carried out polymerase chain reaction amplification on RNA prepared
      from matched PBMC, ITL and the activated (CD25+) subset of ITL using six TCR V
      delta-family specific primers. Although there were differences in the amounts of
      each V delta transcript amplified from PBMC and ITL, there was no difference
      between the two patient groups. No consistent differences were therefore found
      between the gamma delta T cell populations in Graves' and MNG patients, arguing
      against the direct involvement of this T cell subset in the pathogenesis of
      Graves' disease.

PMID- 8252808
TI  - Induction of an anti-Fab, anti-DNA and anti-RNA polymerase I autoantibody
      response network in rabbits immunized with SLE anti-DNA antibody.
AB  - Systemic lupus erythematosus (SLE)-like anti-IgG Fab autoantibodies (autoAb) were
      induced in rabbits by immunization with either human, mouse or rabbit anti-DNA
      Ab. In direct-binding radioimmunoassay (RIA), affinity-purified anti-normal
      rabbit (NR) Fab autoAb cross-reacted with normal mouse (NM) Fab, ssDNA (but not
      dsDNA), poly(dA,dT), and RNA polymerase I (RPI). Affinity-purified anti-NM IgG Ab
      isolated from the same antisera cross-reacted with NR Fab, ssDNA and RPI. In
      inhibition RIA, soluble NR Fab inhibited anti-NR Fab binding to NR Fab and ssDNA,
      but enhanced binding to RPI. In contrast, ssDNA or RPI inhibitors had no effect
      upon autoAb binding to NR Fab. Anti-DNA, anti-RPI and anti-RPI 190 kD subunit
      autoAb, induced by immunization with lupus mouse anti-DNA Ab, also reacted with
      NM Fab, but were idiotypically specific for lupus mouse anti-DNA Fab. Further,
      rabbit anti-DNA and anti-RPI IgG autoAb, induced by immunization with rabbit anti
      DNA IgG, were each idiotypically specific for homologous and autologous rabbit
      anti-ssDNA Fab. Together, these data provide evidence that anti-DNA, anti-RPI and
      anti-Fab autoAb are linked in a complex, multiple-specific and perhaps
      regulatory, immune response idiotype network in SLE.

PMID- 8252810
TI  - Studies on the mechanism of complement-mediated inhibition of antibody binding to
      HIV gp41.
AB  - We have previously demonstrated that HIV envelope gp41 binding to specific
      antibodies decreases after preincubation of fluid-phase gp41 in normal human
      serum. This inhibition is proven to be mediated by the classical complement
      pathway. In this study recombinant gp41 (rgp41) and/or synthetic peptides were
      preadsorbed to solid phase, and then complement (normal human serum/heated human
      serum/purified Clq/heated Clq) and anti-gp41 antibodies were added either after
      each other or simultaneously, and the amounts of bound antibody, and deposited
      C3b, C4b and Clq were measured. Complement-dependent inhibition of antibody
      binding to solid-phase rgp41 was found, and Clq seems to be at least partially
      responsible for this phenomenon. Heating of Clq did not affect this process.
      Higher amounts of anti-gp41 antibodies significantly and dose-dependently
      enhanced C4b and C3b fixation to solid-phase rgp41. In the case of synthetic
      peptides corresponding to the immunodominant region of gp41, significant antibody
      binding to the solid-phase peptides was also detected, and pretreatment of
      peptides preadsorbed to solid phase with normal human serum almost totally
      abolished the antibody binding.

PMID- 8252812
TI  - Spontaneous cytotoxicity of intestinal intraepithelial lymphocytes: clues to the
      mechanism.
AB  - Human intestinal intraepithelial lymphocytes (IEL) demonstrate target cell
      restricted spontaneous cytotoxic (SC) activity that is due to CD2+CD3+CD8+CD16
      CD56- effector cells; they kill epithelial cell (EC) tumours (such as DLD-1 colon
      cancer cells), but not natural killer (NK)-sensitive K-562 cells. The present
      study shows that the measured levels of SC activities by IEL correlated with
      those of autologous lamina propria lymphocytes (LPL), but not with those of
      peripheral blood lymphocytes (PBL). Also, the susceptibilities of DLD-1 cell
      clones to lysis by IEL and PBL effector cells did not correlate, suggesting
      different mechanisms of lysis. Antibody blocking experiments showed that the main
      surface molecules involved in lysis depended on the effector cell type: alpha E
      beta 7 (HML-1) on IEL and CD16 on PBL. No antibody-dependent cell-mediated
      cytotoxicity (ADCC) was demonstrated by IEL, even after stimulation with
      interferon-gamma (IFN-gamma). Few IEL expressed Fc receptors for IgG. This study
      describes further differences between the SC activities of IEL and PBL.

PMID- 8252811
TI  - Variation in interferon-gamma responses to Coxiella burnetii antigens with
      lymphocytes from vaccinated or naturally infected subjects.
AB  - Previous work in our laboratory has shown that lymphocytes from persons
      vaccinated with a formalin-inactivated Phase I Q fever vaccine (Q-Vax CSL Ltd)
      show a mitogenic response to Coxiella burnetii antigens. The mitogenic response
      is the sum of that from various subsets of CD4+, T helper cells, CD8+ T cells and
      probably B cells. It does not distinguish between T helper cell responses leading
      to formation of interferon-gamma (IFN-gamma)--a cytokine responsible for clearing
      intracellular infection with C. burnetii organisms--and responses of other T cell
      subsets which may produce disease-enhancing cytokines. The present study analyses
      (i) the capacity of Q-Vax to induce T cell sensitization which leads to IFN-gamma
      responses on antigen stimulation, and (ii) the immunomodulatory, (down
      regulatory) effects of the Phase I lipopolysaccharide (LPS) of the organism,
      which interacts with monocyte/macrophages to limit IL-2 production and production
      of IFN-gamma by sensitized T lymphocytes.

PMID- 8252813
TI  - Extracts of wheat gluten activate complement via the alternative pathway.
AB  - We studied the ability of wheat gluten and its subfractions to activate
      complement directly. A sensitive sandwich ELISA employing a monoclonal antibody
      (MoAb) to a C9 neoepitope exposed in the terminal complement complex (TCC), a
      functional haemolytic assay for C5b6 generation, and Laurell's electrophoretic
      method of estimating C3 conversion to C3bi were used. On a weight-for-weight
      basis, enzyme solubilized Frazer's fraction three of gluten (FIII) produced
      approximately 75% of the complement activation seen with the potent activator
      zymosan. By contrast, activation with whole insoluble undigested gluten was very
      weak and similar to that seen with ovalbumin or beta-lactoglobulin. The results
      were the same using normal human serum or sera from patients with coeliac
      disease, dermatitis herpetiformis, or hypogammaglobulinaemia as the complement
      source. Activation by both zymosan and FIII was blocked in 0.01 M EDTA, but not
      in 0.01 M EGTA with 0.0025 M magnesium chloride. Zymosan and FIII activated
      complement in a serum from a patient with an intact alternative pathway but
      classical pathway haemolytic activity (CH50) of zero. Preferential heat
      inactivation of the alternative pathway inhibited both zymosan- and FIII-induced
      activation. Our results confirm that FIII is a strong activator of the
      alternative pathway. We discuss how gluten enteropathy might be initiated by
      complement.

PMID- 8252814
TI  - The epidemiology of preterm birth.
AB  - Secular trends in the prevalence of preterm birth and international comparisons
      of the rates of preterm birth are difficult to interpret because of differences,
      both formal and informal, in the registration of extremely preterm births.
      Accurate estimation of gestational age is another problem in the measurement of
      preterm birth. Preterm birth is heterogeneous in several ways. It is
      heterogeneous in terms of the extent to which the birth is preterm (20-27 weeks,
      28-31 weeks or 32-36 weeks of gestation); in whether the birth was elective or
      spontaneous; and among spontaneous idiopathic preterm births, in whether there
      was preterm labour or premature rupture of the membranes. Case-control study
      designs taking account of these subgroups have been a recent feature of
      epidemiologic approaches. The classic social associations of preterm birth--low
      socioeconomic status, extremes of maternal age, primiparity, being unmarried-
      apply to extremely preterm and moderately preterm births as well as to the mildly
      preterm group. The strength of these associations is small compared with factors
      in the prior reproductive history and with medical and obstetric complications of
      the current pregnancy. Recent epidemiological research activities have focused on
      the ways in which risk factors such as physical workload, drugs and alcohol, lack
      of social support and infection might be mediating factors between
      sociodemographic status and preterm birth. As Eastman (1947) pointed out almost
      50 years ago, 'only when the factors causing prematurity are clearly understood
      can any intelligent attempt at prevention be made'.

PMID- 8252815
TI  - Prevention of preterm labour and delivery.
AB  - This chapter describes the French national programme for reduction of preterm
      births which started in 1971. Prevention of preterm labour and delivery in France
      was the objective of a national policy applied to all pregnant women for 10 years
      and more than 700,000 pregnancies every year, and which has continued since the
      end of the initial programme. Prevention is action that must be applied before
      the beginning of disease. The risk analysis was the first step, and showed that
      most known risk factors (young age, previous preterm birth, bleeding during
      pregnancy) could not be changed and could not form the basis of a prevention
      strategy. Other risk factors were described, particularly lifestyle and severity
      of work, which promoted uterine contractions. Uterine contractions can be
      recognized by individual women. Shortening of the cervix is also an important
      risk factor. The intervention strategy involved modifying lifestyle to reduce the
      workload of women, thereby reducing uterine contractions and/or premature
      maturation of the cervix. This national policy was evaluated by two techniques;
      one was performed on successive representative samples of all pregnant French
      women in 1972, 1976 and 1981, and repeated in 1988/9, and the second (from 1971
      to 1982) involved a longitudinal study in a district hospital and included 16,000
      women from the city of Haguenau. Preterm deliveries were significantly reduced in
      France from 7.9% in 1971 to 5.8% in 1981. The reduction was more significant in
      1988-9, with a preterm delivery rate of 4.1%. This was associated with a major
      reduction in early preterm births (before 32 weeks of gestation): 1.6% of births
      in 1972, 0.7% of births in 1981 and 0.5% of births in 1988-9. As this
      intervention was intended for all pregnant women and not as a controlled trial,
      it was not possible to directly demonstrate a causal relationship between the
      intervention and the observed effects. However, it is argued that a close
      relationship exists between the intervention programme and the effective
      reduction of preterm births in France during that time.

PMID- 8252816
TI  - Biochemistry and physiology of preterm labour and delivery.
AB  - Human parturition is associated with profound changes in uterine connective
      tissue affecting mainly the cervix, but the endocrine control of cervical
      ripening remains obscure. Connective tissue changes are also implicated in
      premature rupture of the membranes, a problem often associated with preterm
      delivery, and it is believed that local inflammatory infiltration may play a role
      in both this condition and cervical ripening, but it is difficult to define which
      changes precede parturition and which are a consequence of the trauma of labour.
      Chorioamnionitis can cause preterm labour by provoking the release of
      inflammatory mediators in the decidua/fetal membranes area and it is likely that
      activation of prostaglandin release by decidual macrophages is involved in
      triggering labour. However, the role of macrophages and other bone marrow derived
      cells in normal labour and in labour associated with chorioamnionitis needs to be
      defined. It is likely that treatment with a combination of antibiotics and
      prostaglandin synthase inhibitors and/or other anti-inflammatory drugs is the
      most appropriate therapeutic approach. Idiopathic preterm labour and spontaneous
      labour at term are probably due to changes in the sensitivity of the myometrium
      to endogenous agonists. Recent progress in cell signalling pathways, such as the
      characterization of regulatory G proteins and the cloning of hormone receptors,
      should clarify the mechanism of action of relaxing and contracting agents on
      myometrial cells and should provide the means for the development of new
      therapeutic agents of high effectiveness and selectivity. This approach should
      result in better management of both term and preterm labour.

PMID- 8252817
TI  - Immunoendocrinology of preterm labour and delivery.

PMID- 8252818
TI  - Oxytocin antagonists in preterm labour and delivery.
AB  - Evidence has been gained that an oxytocin receptor antagonist given by
      intravenous infusion effectively stops uterine contractions in threatened as well
      as in actual preterm labour. The findings suggest that the increase of oxytocin
      receptors is aetiologically important in uncomplicated preterm labour. Oxytocin
      antagonists could therefore be an attractive alternative to currently used drugs
      by virtue of their high specificity and lack of serious side-effects. Their use
      in prophylactic and maintenance therapy may be greater when modified analogues
      have been developed that allow non-parenteral therapy.

PMID- 8252819
TI  - Preparing the fetus for preterm birth.
AB  - Optimum perinatal outcome is only achieved by the prevention of premature birth.
      When preterm delivery is unavoidable, antenatal pharmacologic therapy will result
      in a reduction in the leading causes of neonatal morbidity and mortality, mainly
      respiratory distress syndrome (RDS), BPD, intraventricular haemorrhage (IVH) and
      sepsis. These treatments combined with meticulous intrapartum management will
      result in significant improvements in the neonatal and long-term outcome in the
      premature baby.

PMID- 8252820
TI  - Preterm labour and delivery: psychological sequelae.
AB  - The psychological care of preterm babies and their families is challenging and at
      least as demanding for staff as the technical aspects of care. There is growing
      evidence for the effectiveness of therapeutic interventions in this area, thus
      ensuring the optimum outcome for the baby, the family and the staff.

PMID- 8252821
TI  - [Sudomotor dysfunction in Parkinson's disease].
AB  - Sudomotor function was evaluated by using the sympathetic skin response (SSR) and
      the sweat response to intradermal acetylcholine (ACh) injection in 69 patients
      with Parkinson's diseases (PD). The incidence of SSR abnormality (34.8%) was as
      high as that of orthostatic hypotension (30.4%) and increased with the severity
      of the illness. Anticholinergic drug did not influence the incidence of SSR
      abnormality. Therefore, the SSR is useful in evaluating sudomotor efferent
      pathway in PD patients. Moreover, in all patients, sweat response to ACh showed a
      reduced number of excitable sweat glands and a low volume of sweat. In a patient
      in whom sweat response to ACh was markedly impaired, however, the density of
      acetylcholinesterase-positive unmyelinated fibers in biopsied sural nerve was in
      normal range. Therefore, this is considered to indicate functional disturbance of
      the postganglionic sympathetic fibers in PD patients, without morphological
      changes.

PMID- 8252822
TI  - [Three cases of herpes simplex virus type 2 myelitis--detection of HSV2 DNA in
      cerebrospinal fluid].
AB  - Polymerase chain reaction (PCR) technique has been successfully used to detect
      herpes simplex virus (HSV) from patients with HSV encephalitis. By PCR assay
      capable of differentiating HSV1 and 2, we detected HSV 2 DNA in cerebrospinal
      fluid (CSF) from patients with HSV myelitis and discussed the clinical findings.
      Three cases of HSV myelitis (a 49-year-old female, two 38- and 44-year-old males)
      were studied. All cases were characterized by transverse myelopathy of the
      thoracic cord, and two patients had recurrence. In all cases HSV1 antibodies were
      significantly elevated in serum and CSF. We used 500 microliters of CSF for PCR,
      and prepared one common upstream primer and two type specific downstream primers
      for HSV1 and HSV2. Using three primers simultaneously different sizes of PCR
      products were amplified from HSV1 and HSV2 DNA. PCR products subjected to
      electrophoresis on 1.2% agarose and stained with ethidium bromide. Still more
      southern blot hybridization was performed to detect DNA by 35S-end-labelled
      oligonucleotide prove. HSV2 DNA was amplified from CSF in all cases by PCR, and
      HSV2 DNA was detected at both first and second episode in two relapsing myelitis.
      No case of relapsing myelitis by HSV2 has been reported. The PCR technique is
      useful for diagnosis of HSV1 and 2 myelitis, and its would suggest that some
      patients of idiopathic myelopathy could be due to HSV2 myelitis and HSV2 myelitis
      may not be rare.

PMID- 8252823
TI  - [Clinical significance of pontine high signals identified on magnetic resonance
      imaging].
AB  - Spin-echo magnetic resonance imaging (MRI) was evaluated to 530 cases in order to
      investigate the clinical, significance of pontine high signals. The subjects
      comprised 109 cases of pontine infarction with high signal on T2-weighted image
      and low signal on T1-weighted image (PI group), 145 of pontine high signal with
      high signal on T2-weighted image but normal signal on T1-weighted image (PH
      group) and 276 of age-matched control without abnormality either on T1 or T2
      weighted images (AC group). Subjective complaints such as vertigo-dizziness were
      more frequent in the PH group than in the PI group. In both PI and PH groups,
      periventricular hyperintensity as well as subcortical high signals in the
      supratentorium were more severe than in the AC group. These degrees were higher
      in the PI group than in the PH group. In conclusion, PH as well as PI may result
      from diffuse arteriosclerosis and PH is considered to be an early finding of
      pontine ischemia.

PMID- 8252824
TI  - [Alteration of inositol 1,4,5-trisphosphate receptor binding after 6-hour
      hemispheric ischemia in the gerbil brain].
AB  - Inositol 1,4,5-trisphosphate (IP3) has recently been known to play vital roles as
      one of the second messengers to control intracellular metabolism of calcium ion.
      Therefore, alterations of IP3 receptor binding and local cerebral blood flow
      (1CBF) were evaluated at 6 hours after occlusion of the right common carotid
      artery in the gerbil brain. The autoradiographic method developed in our
      laboratory enabled us to measure both parameters in the same brain. Animals
      attaining more than 5 in their ischemic scores, which were assessed at 1 hour
      after the occlusion, were utilized. LCBF was measured by the 14C-iodoantipyrine
      method at the end of the experiment. After frozen brains were cut into serial
      slices on a cryostat, the IP3 receptor binding was evaluated in vitro by using 3H
      inositol 1,4,5-trisphosphate as the ligand. LCBF fell below 10 ml/100 g/min in
      most of the cerebral regions on the occluded side. In contrast a significant
      reduction in IP3 binding was noted only in the hippocampus CA1 on the occluded
      side. The IP3 binding tended to decrease when the values of 1CBF were reduced
      below 20 ml/100 g/min in this region. These findings suggest that the selective
      alteration of IP3 receptor binding in the hippocampus CA1 may be closely
      associated with the selective vulnerability of this region to ischemia.

PMID- 8252825
TI  - [Paramedian dorsal syndrome of mesencephalic tegmentum].
AB  - Two cases of brainstem infarction involving a unilateral side of the midbrain
      tegmentum showed a peculiar ocular symptom complex. The ocular syndrome consisted
      of (1) oculomotor palsy ipsilateral to the lesion, (2) monocular eyelid
      retraction and upward gaze palsy contralateral to the lesion, and (3) conjugate
      downward gaze and convergence palsy. By computed tomography and cerebral
      angiography, the lesion shared by the two cases was identified in the territory
      of median mesencephalic rami originating from the posterior cerebral artery. The
      lesion involved oculomotor nucleus on a side. Contralateral monocular symptoms
      and conjugate palsies could be attributed to a damage in their supranuclear
      tracts. Considering with two similar cases in the literature, it is strongly
      suggested that a unilateral ischemic lesion of the paramedian dorsal part of the
      midbrain tegmentum is responsible for this syndrome. Bilateral or unilateral
      eyelid retraction (Collier's sign) was considered to locate a lesion in the
      posterior commisure by Collier himself. The posterior commisure is, however, not
      involved in our two cases, and a paramedian lesion of the midbrain tegmentum
      deviated to a side may cause contralateral eyelid retraction. A combination of
      ophthalmoplegia ipsilateral to the lesion, upward or lateral (in the opposite
      direction to the lesion) gaze palsy, and hemiataxia on the contralateral side
      resembling our second case is sometimes erroneously called Nothnagel's syndrome.
      Nothnagel mentioned symptomatology of the quadrigeminal bodies for local
      diagnosis in his text in which he did not describe this combination of signs.

PMID- 8252826
TI  - [A case of cough hemiplegia].
AB  - We reported a patient with internal carotid artery occlusion (ICAO) who developed
      cough-induced transient hemiplegia. A 63-year-old man with chronic obstructive
      pulmonary disease experienced several episodes of cough-induced left hemiplegia
      during drinking and smoking. Selective cerebral angiography demonstrated right
      ICAO at the vessel origin, with 50% stenosis of the left internal carotid artery.
      Collateral circulation from the right external to internal carotid artery
      branches and through the anterior communicating artery was poorly observed on the
      angiograms. Right middle cerebral artery branches were well visualized on
      vertebral angiograms at the late phase through the posterior and anterior
      pericallosal arteries. Due to this collateral blood supply, the right middle
      cerebral artery territory formed the most distal part of the cerebral circulation
      and was vulnerable to a reduction of cerebral blood flow. We considered that
      systemic hemodynamic disturbances by identical mechanisms to those observed in
      cough syncope may have brought about transient ischemia in the right middle
      cerebral artery territory which was manifested in the patient's unusual clinical
      presentation of ICAO "cough hemiplegia".

PMID- 8252827
TI  - [A case of Klippel-Trenaunay-Weber syndrome--special reference to myelopathy].
AB  - A 49-year-old woman with Klippel-Trenaunay-Weber syndrome (KTW) is reported. She
      had characteristic features of KTW; cutaneous angiomas on her back, left knee and
      both plantae, varicosities on both legs, and hypertrophy of the left leg. In
      addition she had rare complications of KTW; asymmetric skull bone, hemicranial
      hypertrophy, kyphosoliosis, idiopathic hypoparathyroidism, and abnormal length of
      the dactyl. Her hemicranial hypertrophy was examined by CT scan, MRI and
      angiography. Her right hemicranial volume was enlarged and her left lateral
      ventricle was enlarged. The T2-weighted MRI imaging demonstrated high signal
      intensity beside the right lateral ventricle and in the right basal ganglia.
      Cerebrovascular anomalies were not revealed. She also had neurological
      manifestations of KTW that are rarely seen in adult cases; mental retardation,
      and myelopathy. The anti-HTLV-I antibodies in serum and cerebrospinal fluid were
      positive, so it was thought for her to have HTLV-I associated myelopathy (HAM).
      She was treated with peroral prednisolone and alpha-interferon (intramuscular),
      which improved her ability to walk. It is known that kyphosis sometimes makes the
      disorder of spinal cord. Although KTW is known to be associated with the spinal
      arteriovenous malformation, several examinations did not reveal the spinal
      vascular anomalies in this case. So we think the myelopathy of this case was
      caused mainly by the kyphoscoliosis and HAM.

PMID- 8252828
TI  - [A case of flaccid paraplegia associated with HTLV-I infection].
AB  - A 63-year-old female began to have progressive gait disturbance at the age of 50.
      Neurologic examination revealed weakness and hypotonus of bilateral leg muscles.
      Deep tendon reflexes were hypoactive with positive Babinski sign and vibration
      sense was diminished in the legs. HTLV-I antibody titers were elevated both in
      serum (x 131,072) and in CSF (x 512). The result of nerve conduction velocities
      and short latency somatosensory evoked potentials suggested mild peripheral nerve
      lesion. Needle EMG studies showed myogenic changes in the upper limbs and also,
      neurogenic changes in the lower limbs. Histological examination verified mild
      myogenic changes in biopsied deltoid muscle and neurogenic and myogenic changes
      in the quadriceps femoris muscle, with ragged-red fibers. We consider that this
      patient has myelopathy, myopathy, peripheral neuropathy and anterior horn cell
      involvement associated HTLV-I infection. The relationship between HTLV-I
      infection and mitochondrial abnormalities of the biopsied muscles remains
      unclear.

PMID- 8252829
TI  - [A case of pseudoxanthoma elasticum associated with asymptomatic multiple
      cerebral infarction, hypothyroidism, glucose tolerance abnormality and multiple
      congenital anomalies].
AB  - We report a case of pseudoxanthoma elasticum (PXE) associated with asymptomatic
      multiple cerebral infarction on magnetic resonance imaging (MRI),
      endocrinological abnormalities and multiple congenital physical anomalies. A 40
      year-old woman suddenly developed paresthesia in the right half of the body.
      Physical examination demonstrated loosening of the skin and yellowish papules in
      the neck and axilla, retinal angioid streaks, cardiac mitral regurgitation,
      congenital aplasia of the uterus and vagina, and congenital abduction palsy of
      the right eye. The biopsy of the papules in the neck showed typical features of
      PXE. Laboratory tests revealed positive antibodies to thyroglobulin and
      microsome, high TSH level with normal free T3 and T4, and impaired glucose
      tolerance. The laboratory data and the findings of ultrasonic examination on the
      thyroid suggested presence of Hashimoto's disease. MRI of the brain demonstrated
      multiple cerebral infarcts through they were asymptomatic. MRI failed to clarify
      the lesion responsible for the hemiparesthesia. Carotid arteriography showed
      slight stenosis with ulceration near the origin of the right internal carotid
      artery, and severe stenosis of the horizontal portion of the right middle
      cerebral artery. MRI study of the brain is recommended in PXE patients since the
      complication of brain pathology worsens the prognosis of the disease.

PMID- 8252830
TI  - [Propriospinal myoclonus--a case report].
AB  - Propriospinal myoclonus is one type of myoclonus that is proposed to originate in
      the spinal cord and spread up and down via propriospinal tract. There are a few
      reports describing the detailed electrophysiological findings of this myoclonus.
      In this communication, we present the results of electrophysiological analysis of
      a patient with propriospinal myoclonus. A 23-year-old woman suddenly noticed
      abdominal pain, which spontaneously faded in a few hours. Irregular involuntary
      flexion jerks of the trunk appeared spontaneously without pain or hiccups after
      this episode. It involved the bilateral axial muscles; sternocleidomastoid
      muscles (SCM), paravertebral muscles (PVM), abdominal muscles (ABD), and
      intercostal muscles (ICM), but not the limb muscles. It was worsened by the
      mental stress, but not by her posture or position. While she slept, the jerks
      were not observed. Routine laboratory examinations were all normal. Magnetic
      resonance imaging of the spinal cord revealed no abnormalities. The
      electrophysiological studies done on this patient are polymyography, back
      averaging of the EEG activity preceding spontaneous jerks (jerk-locked averaging
      (JLA), and movement related cerebral potential (MRCP) preceding the involuntary
      jerks and voluntary abdominal movements. No EEG activities preceding the
      myoclonus were demonstrated by JLA or MRCP. No MRCP recorded preceding the
      myoclonus suggests that the jerk is not a self-initiated or externally triggered
      voluntary movement. Polymyography revealed that the jerks involved the bilateral
      axial muscles including SCM, PVM, ICM, and ABD, but not the limb muscles.
      Homologous muscles were activated synchronously. The duration of EMG bursts was
      variable ranging 50 to 250 ms in these muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252831
TI  - [A case of multiple system atrophy presenting a regular involuntary movement of
      the neck muscles synchronous with respiration].
AB  - A patient with multiple system atrophy developed a regular, rhythmic involuntary
      movement of the neck muscles which appeared synchronous with respiration and
      could be described as "rocking-of-the-head". He had been treated with
      antiparkinsonian drugs such as L-dopa, L-dopa/carbidopa, amantadine hydrochloride
      and trihexiphenidyl hydrochloride for approximately one year. A fluoroscopic
      study assured that the involuntary "rocking-of-the-head" movement synchronized
      with the diaphragmatic up-and-down movement. A polygraphic study showed that the
      accelerometer curve which reflected the rocking movement of the head oscillated
      at approximately 0.7 Hz and synchronized with the surface EMG discharges of the
      right sternocleidomastoid muscle and the nasal flow curve. This involuntary
      movement was seen almost all day long as well as asleep but severest usually in
      the afternoon. Discontinuation of trihexiphenidyl hydrochloride alone made the
      involuntary movement less severe but never suppressed it completely. Resumption
      of the drug made the involuntary movement as severe as it had been.
      Discontinuation of L-dopa, L-dopa/carbidopa and amantadine hydrochloride was
      followed by disappearance of the involuntary movement in a day or so, in spite of
      continued intake of trihexiphenidyl hydrochloride. Rigidity and bradykinesia
      induced by discontinuation of these drugs, however, made it necessary to resume
      them. As a result the involuntary movement again exacerbated.

PMID- 8252832
TI  - [The effects of nicotine on a patient with spinocerebellar degeneration whose
      symptoms temporarily exacerbated by cigarette smoking].
AB  - The purpose of the present study was to elucidate the influences of nicotine on a
      patient with spinocerebellar degeneration whose symptoms temporarily exacerbated
      by cigarette smoking. We have examined the influences of nicotine gum on
      cerebellar ataxia. Limb ataxia, dysarthria and truncal titubation were maximally
      aggravated 15 min after nicotine gum chewing, which paralleled blood nicotine
      level. Specific increased accumulation of 123I-IMP was observed in the cerebellum
      15 min after nicotine gum load by 123I-IMP-SPECT. On the other hand, in a control
      with spinocerebellar degeneration whose symptoms not changed by nicotine gum
      load, the specific finding on 123I-IMP-SPECT was not detected. These findings
      suggested a direct effect of nicotine on the cerebellum.

PMID- 8252833
TI  - [A familial case of DRPLA diagnosed by an autopsy associated with
      hemoglobinopathy (Hb Takamatsu)].
AB  - The patient first noticed general muscle stiffness at the age of 36. Two years
      later, she suffered from a tonic-clonic seizure which brought her to a hospital
      for the first time. Choreoathetoid movement, ataxia and cognitive deficit were
      apparent. At the age of 44, tonic-clonic seizures became more frequent and she
      was admitted to our hospital as being status epilepticus. After the cessation of
      clinical seizures, she became appllic. Gradual increase of atrophic changes in
      cerebrum, cerebellum and brain stem were observed by MRI and CT. Hematological
      study showed that she had abnormal hemoglobin, Hb Takamatsu. Four of her five
      children were clinically examined; all of them showed abnormal EEG findings;
      three being mentally retarded and had clinical generalized convulsive seizures;
      two had hemoglobinopathy (Hb Takamatsu). The patient died from sepsis at the age
      of 50 and the autopsy was carried out. The brain weighed 930 gram. Histological
      findings confirmed the diagnosis of dentato-rubro-pallido-luysian atrophy;
      neuronal loss accompanied by gliosis in dentate nuclei, red nuclei, lateral part
      of globus pallidus, and subthalamic nuclei. The coincidence of the hereditary
      traits of two independent diseases, DRPLA and familial hemoglobinopathy (Hb
      Takamatsu) suggests closeness of their genetic loci.

PMID- 8252834
TI  - [HTLV-I associated myelopathy presenting with profound atrophy of unilateral
      lower limb].
AB  - A 63-year-old woman had suffered from progressive weakness and wasting of the
      right lower limb for seven years. In the lower limbs, there were profound
      muscular atrophy and weakness on the right, and mild weakness with spasticity on
      the left. Muscle strength of the upper limbs was normal. Sensory examination was
      normal except for paresthesias below the right knee. Anti-HTLV-I antibody titer
      was raised both in serum and in the CSF. Motor nerve conduction studies of the
      lower limbs showed small compound muscle action potentials and somewhat slow
      conduction velocities, more evident in the right side. F-wave was evoked only in
      the left tibial nerve and its latency was increased. Sensory nerve conduction
      studies were normal in the lower limbs. Somatosensory evoked potentials (SEPs)
      after tibial nerve stimulation at the ankles showed increased interpeak latencies
      between lumbar N20 and scalp P37. Nerve conduction studies in the upper limb were
      normal. Single fiber electromyography suggested anterior horn involvement not
      only in the lumbosacral cord but also in the cervical cord. Weakness and
      spasticity improved after oral administration of prednisolone. The SEPs findings
      and a favorable response to prednisolone excluded the possibility of amyotrophic
      lateral sclerosis. This case is a clinical variant of HTLV-I-associated
      myelopathy presenting profound atrophy of unilateral lower limb.

PMID- 8252835
TI  - [Markedly decreased cardiac uptake with 123I-MIBG scintigraphy in a case of pure
      progressive autonomic failure].
AB  - A 70-year-old man with about 25 years' history of autonomic nervous system
      disturbances including orthostatic hypotension is presented. He had had no
      extrapyramidal and cerebellar signs, and was diagnosed as having pure progressive
      autonomic failure. His cardiac imaging with 123I labeled MIBG
      (metaiodobenzylguanidine) showed extremely diminished uptake, but the imaging
      with 201-thallium showed a normal cardiac uptake. Those results indicate non
      cardiac disease-associated (neurogenic) postganglionic sympathetic fiber
      abnormality innervating the heart. Also, adrenomedullary imaging with 123I
      labeled MIBG showed no adrenal image, which suggests the possibility that there
      should be dysfunction in the adrenal medulla of this patient. This imaging study
      is thought to be useful for evaluating autonomic nervous system function in
      neurologic diseases.

PMID- 8252836
TI  - [Acute respiratory arrest associated with medullary lesion in a case of multiple
      sclerosis].
AB  - We present a case history of a patient with multiple sclerosis who developed an
      abrupt onset of respiratory arrest associated with medullary lesion. A 27-year
      old man developed shallow, totally irregular, ataxic respirations with
      aggravation of bulbar palsy and quadriplegia in the course of multiple sclerosis.
      As respiration was almost arrested, artificial respiration was started and
      continued for five days. Respiration was almost normal after 16 days from the
      onset of respiratory arrest. MRI showed bilateral, medullary lesions without
      upper cervical lesions. Pyramidal tracts, medial lemnisci, and paramedian
      reticular formations in medulla were damaged bilaterally. We supposed that the
      medullary lesions involved dual respiratory systems: a voluntary system and an
      automatic system, and caused acute respiratory arrest.

PMID- 8252837
TI  - An integrated model of estrogen receptor action.

PMID- 8252838
TI  - Effects of continuous administration of gonadotropin-releasing hormone (GnRH) or
      a potent GnRH analogue on blood luteinizing hormone and testosterone
      concentrations in prepubertal bulls.
AB  - The objective was to determine if continuous administration of gonadotropin
      releasing hormone (GnRH) or a potent analogue (GnRH-A) for 28 or 56 d would
      decrease blood concentrations of luteinizing hormone (LH) and testosterone (T) in
      5-month old bull calves. Treatments (5 calves/treatment), using a completely
      randomized design, were: control (vehicle), 3.3, 10 and 30 micrograms GnRH, and
      3.3 and 10 micrograms GnRH-A (Leuprolide) per kg bodyweight/d for 28 d,
      administered via subcutaneously implanted mini-osmotic pumps. A second pump was
      implanted on day 28 in controls and bulls receiving 10 micrograms GnRH-A until
      day 56. Blood samples were taken every second day for plasma LH and T
      concentrations, and every 15 min for 6 hr on days 1, 14 and 27 (and days 40 and
      55 where applicable) for plasma LH concentrations. There was an increase (P <
      0.05) in basal plasma LH in response to GnRH and GnRH-A on day 1 (1.6, 2.1, 2.1,
      2.5, 2.1 and 1.9 ng/ml for control, 3.3, 10 and 30 micrograms GnRH, and 3.3 and
      10 micrograms GnRH-A, respectively; pooled s.e.d. = 0.2), but not on days 14 or
      27. The number of LH pulses/6 hr was similar on day 1 for GnRH-treated and
      control calves, but there was a linear decrease (P < 0.05) in pulse frequency in
      response to GnRH doses on days 14 (1.8, 1.2, 0.6 and 0.0 for control, 3.3, 10 and
      30 micrograms GnRH; s.e.d. = 0.5) and 27 (1.8, 1.0, 0.0 and 0.0; s.e.d. = 0.3).
      On days 1, 14 and 27, both GnRH-A doses suppressed (P < 0.05) LH pulsatility.
      GnRH (days 1-14) and GnRH-A (days 1-27) increased (P < 0.05) plasma T in a dose
      dependent manner. Mean T was greater (P < 0.05) in 10 micrograms GnRH-A-treated
      than in control calves during days 29-41 (4.6 and 1.8 ng/ml; s.e.d. = 0.6) and
      days 43-55 (4.1 and 1.8 ng/ml; s.e.d. = 0.4). In conclusion, continuous
      administration of GnRH or GnRH-A to 5-month old bulls for 28 or 56 d chronically
      decreased LH pulse frequency, had no effect on basal LH, but increased
      testosterone concentrations.

PMID- 8252839
TI  - Insulin responsiveness to glucose and tissue responsiveness to insulin during
      lactation in dairy cows.
AB  - The hyperglycemic clamp and hyperinsulinemic euglycemic clamp techniques were
      conducted to assess insulin responsiveness to glucose and tissue responsiveness
      to insulin in lactating and nonlactating Holstein cows. In the hyperglycemic
      clamp experiment, blood glucose concentrations were clamped at 50 mg/dl above the
      pre-infusion values by variable rates of glucose infusion. The mean plasma
      insulin increments over the baseline (insulin responsiveness to glucose) during
      hyperglycemia were lower (P < .05) in lactating cows than in nonlactating cows
      (23 vs. 102 microU/ml). In the hyperinsulinemic euglycemic clamp experiment,
      insulin was infused at the constant rate of 6.0 mU.kgBW-1.min-1 for 2 hr, and
      glucose was concomitantly infused at a variable rate to maintain the pre-infusion
      concentrations of blood glucose. Glucose infusion rates (tissue responsiveness to
      insulin) were similar (3.2 mg.kgBW-1.min-1) for lactating and nonlactating cows.
      It is concluded that insulin responsiveness to glucose is reduced, and tissue
      responsiveness to insulin remains unchanged during lactation in Holstein cows.

PMID- 8252840
TI  - Study of the hepatic growth hormone (GH) receptor at different ages in chickens
      selected for a good feed conversion (FC) and a fast weight gain (GL).
AB  - The influence of genetic selection for improved feed conversion (FC) and fast
      growth (GL) in broiler chickens, on the hepatic growth hormone receptor was
      investigated as a function of age. Selection for improved feed conversion
      resulted in lean chickens, whereas selection for fast growth resulted in fat
      chickens. Growth hormone receptor characteristics were determined in liver
      microsomal fractions and plasma GH concentrations were measured by
      radioimmunoassay. Embryos from the FC line showed higher specific GH binding than
      GL embryos at day 16 of embryonic development only (P < 0.05). On day 18 of
      embryonic development, the FC line had slightly more GH receptors than the GL
      line (P < 0.05), whereas simultaneous plasma GH concentrations were greater in
      the GL line. The effect of selection on hepatic growth hormone binding was
      greatest in 4 week old growing chicks at which age the GL line showed a 2- to 3
      fold higher % of specific binding than the FC line (P < 0.001). The difference at
      this stage is probably due to down regulation of the receptor by the
      significantly higher GH concentrations in the FC line. The adult GL chickens also
      showed higher specific binding than FC, but the difference was less pronounced
      than in the growing stage (P < 0.05). This was due to a higher number of GH
      receptors, while receptor affinity was unchanged. Because no line difference in
      plasma GH concentrations was found in adult hens, other unknown mechanisms
      probably play a role in determining differences in GH receptor binding between
      these selected lines at older ages.

PMID- 8252841
TI  - Detection of mRNA for inhibin alpha- and beta A-subunits in bovine ovarian
      tissues and the effect of in vivo administration of GNRH.
AB  - The aims of these studies were to determine which types of bovine ovarian tissue
      contain mRNA for inhibin/activin subunits and whether administration of GnRH
      influences concentration of these mRNAs. In experiment (exp.) one, cows in the
      luteal phase of the estrous cycle were given prostaglandin F2 alpha (PGF2 alpha)
      to induce luteal regression and injected after 40 hr with saline (n = 5) or 100
      micrograms GnRH (n = 6). Ovaries were removed 6 hr later. In exp. two,
      unilaterally ovariectomized (OVX) heifers (n = 33) in the luteal phase of their
      estrous cycle were given PGF2 alpha to induce luteal regression. Twelve heifers
      were OVX without injection of GnRH at 24 (n = 6) or 40 hr (n = 6) after PGF2
      alpha. The remaining heifers (n = 21) were given 100 micrograms GnRH at 40 hr
      after PGF2 alpha injection and OVX 8 (n = 4), 16 (n = 5), 24 (n = 6) or 48 (n =
      6) hr after GnRH injection. Total cellular RNA was isolated from large follicles
      (exp. one and two), small-medium follicles and stromal tissue (SMS) and corpora
      lutea (CL; exp. one) tissues and analyzed by dot blot and Northern blot
      techniques by hybridizing with cDNA probes for human inhibin/activin alpha- and
      beta A-subunits. Large follicles were classified as steroidogenically active (EA)
      if follicular fluid (FF) concentration of estradiol-17 beta (E2) was greater than
      progesterone (P4), or if P4 and E2 concentrations in FF were greater than 100
      ng/ml, and estrogen inactive (EI) if FF concentration of E2 and P4 did not
      satisfy these criteria. In exp. one, mRNA for the alpha-subunit was primarily
      expressed in EA follicles, and detectable in EI follicles, SMS, and CL while beta
      A-subunit mRNA was detected only in large EA follicles and a few SMS samples. The
      mRNA (x +/- SEM fmoles/mg DNA) for both subunits of inhibin/activin was higher (P
      < .05) in EA follicles from GnRH-treated cows (alpha = 210.2 +/- 38.6; beta A =
      376.9 +/- 41.0) than in EA follicles from control cows (alpha = 102.5 +/- 28.6;
      beta A = 170.8 +/- 57.6). Concentration of mRNA for the alpha-subunit of inhibin
      in other ovarian tissues was not different (P > .10) between saline and GnRH
      treatments.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8252842
TI  - Influence of follicular maturation on the deposition of fibronectin by chicken
      granulosa cells in vitro--effect of 8-bromo cyclic AMP.
AB  - Fibronectin deposition by avian granulosa cells and the effect of 8-bromo cAMP (8
      br-cAMP) on this process was investigated in vitro. Granulosa cells obtained from
      the first (F1) and third (F3) largest preovulatory follicles and from small
      yellow follicles (SYF) were incubated in serum free medium 199 for 12 or 24 hr
      with and without 8-br-cAMP. Fibronectin deposited in incubation wells secreted in
      medium or associated with cells was measured by ELISA. Basal fibronectin
      deposition increased with time and was greatest for F1 cells. Within 12 hr, 8-br
      cAMP enhanced fibronectin deposition dose-dependently by F3 and SYF cells, but
      not by F1 cells. The amount of fibronectin deposition caused by 8-br-cAMP (which
      was greater after 24 hr incubation) was 0.10- to 0.16-fold for F1 cells; 0.20- to
      0.81-fold for F3 cells and more than 30-fold for SYF cells. Fibronectin secreted
      in the medium by unstimulated cells was also greatest in F1 cells. 8-bromo cAMP
      stimulated fibronectin secretion in medium dose-dependently by F3 and SYF cells,
      however, it had only a marginal stimulatory effect on this process in F1 cells.
      Cell-associated fibronectin was not increased significantly by 8-br-cAMP in F1,
      F3 or SYF cells. Total (deposited plus medium plus cell associated) fibronectin
      production was elevated in dose- and time-dependent manner by 8-br-cAMP in F3 and
      SYF cells, but only at high concentrations in F1 cells. Like deposited
      fibronectin, the relative effect of 8-br-cAMP on fibronectin secreted in the
      medium and on total fibronectin production was greatest in immature SYF cells.
      These results demonstrate that fibronectin synthesized and deposited by
      unstimulated chicken granulosa cells in vitro increase concomitantly with
      follicular maturation and cellular differentiation, and the relative change in
      fibronectin production caused by 8-br-cAMP was greatest in immature SYF cells.

PMID- 8252843
TI  - Steroid synthesis by equine conceptuses between days 7 and 14 and endometrial
      steroid metabolism.
AB  - The objective of this study was to determine if changes in steroid synthesis
      occurred in the horse blastocyst about the time of maternal recognition of
      pregnancy. Embryos collected between days 7.5 and 14.5 were incubated for 8 hr in
      vitro in HAM's F10 containing radiolabelled pregnenolone. The steroid metabolites
      in the incubation medium were separated by reverse phase HPLC and the major peaks
      expressed as a percentage of total metabolites. It was found that there were no
      major changes in the profile of metabolites throughout the period of study,
      although there was increased conversion as the conceptuses developed. It was
      found that the major metabolite produced was 17 alpha-hydroxyprogesterone and not
      estradiol as expected. A second experiment was conducted to determine if 17 alpha
      hydroxyprogesterone was metabolized by endometrial tissue. Endometrial biopsies
      from anestrous mares and from pregnant and nonpregnant mares at day 11 were
      incubated with radiolabelled 17 alpha-hydroxyprogesterone, progesterone or
      pregnenolone. The 17 alpha-hydroxyprogesterone, but not progesterone nor
      pregnenolone, was converted to a more polar metabolite in all groups. Production
      of this metabolite was significant greater in the anestrous mares. This
      metabolite has not been unidentified conclusively. Thus, results of this study
      show that 17 alpha-hydroxyprogesterone is the major steroid synthesized by the
      equine blastocyst and that this steroid is further metabolized to an unidentified
      steroid by the endometrium. These steroids could play a role in conceptus
      development or maternal recognition of pregnancy.

PMID- 8252844
TI  - Age-related plasma concentrations of growth hormone (GH) and insulin-like growth
      factor I(IGF-I) in Great Dane pups fed different dietary levels of protein.
AB  - During a 20-week study, 17 Great Dane dogs, 7 weeks of age, were used to study
      the influence of 3 isoenergetic diets differing in dietary protein levels (i.e.,
      31.6%, 23.1%, and 14.6% on a dry matter basis) on body weight, growth in length,
      and age-related plasma GH and IGF levels. Significant differences occurred in
      weekly body weight gain of the high- and low- protein groups only in the fourth
      week of the study. There was a significant decrease in mean basal plasma GH
      values with time from 14.8 +/- 2.2, 13.7 +/- 2.2, and 14.3 +/- 2.2 micrograms/l
      in the second week to 2.3 +/- 1, 0.7 +/- 0.4, and 1.8 +/- 0.7 microgram/l in the
      last week of the study for the high-, normal- and low-protein groups,
      respectively. Differences among groups were not significant. There was a positive
      correlation between the decrease in weekly body weight gain and plasma GH
      concentration in all 3 groups. IGF-I concentrations in plasma did not change
      consistently with age and were not correlated with plasma GH values. Significant
      differences in plasma IGF-I concentrations were found between groups at 15 weeks
      of age. Preliminary results of measurements of IGF receptors in the membranes of
      growth plate cartilage of long bones of 5 dogs revealed that homologous
      displacement of 125I-labeled IGF-I binding resulted in similar curves. A single
      binding site for IGF-I was assumed. The large number of type II IGF receptors in
      7 dogs suggests a key role for IGF-II in postnatal skeletal growth. The results
      of this study demonstrate for the first time that in Great Dane pups basal GH
      concentrations in plasma decrease between 7 and 27 weeks of age, parallel to the
      decrease in growth velocity, whereas the plasma IGF-I concentrations remain
      relatively high and unchanged. The slight but statistically significant effects
      of low-protein feeding on growth velocity and circulating concentrations of IGF-I
      indicate that a diet containing 14.6% protein on a dry matter basis (13% protein
      as metabolizable energy) is marginal for growing Great Dane pups between 7 and 17
      weeks of age.

PMID- 8252845
TI  - Age-related changes in secretion rate and post-secretory metabolism of growth
      hormone in swine.
AB  - The effect of age on growth hormone (GH) metabolism and GH-releasing factor (GRF)
      induced GH concentrations were studied in 7 young (3 mo, 39 kg) and 7 old (30 mo,
      156 kg) Yorkshire x Landrace female pigs. Jugular catheters were surgically
      inserted and 60 hr later total serum volume was determined. The following day,
      all animals were infused for 3 hr with GH (30.3 ng.min/kg B.W.) in order to
      calculate GH metabolic clearance rate (MCR), secretion rate (SR) and half-life (t
      1/2). Two days later, 15 micrograms/kg of GRF was injected i.v. into all pigs. On
      a per animal basis, aging increased (P < .01) MCR (299 vs 132 ml/min), SR (714 vs
      422 ng/min) and serum volume (6.6 vs 2.01), whereas t1/2 was unaltered (P > .1).
      Basal GH concentrations were lower in older pigs (P < .10) but the GRF-induced GH
      concentrations (measured as GH peak or area under the curve, AUC) were not
      affected by age (P > .1). Yet, when induced total GH secretion (AUC x MCR) and
      average total serum GH (mean GH post-injection x serum volume) were calculated
      per pig, these variables significantly increased between 3 and 30 mo of age.
      Basal IGF-I concentrations were lower in older pigs (P < .01), yet, there was a
      tendency (P = .10) for these pigs to show a greater IGF-I response to GH
      infusion. The present data therefore indicate that age alters both SR and post
      secretory metabolism of GH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252846
TI  - Paroxetine: a new serotonin reuptake inhibitor for the treatment of depression.
AB  - The introduction of the selective serotonin reuptake inhibitors (SSRIs) over the
      past several years has made a major impact on the treatment of depression and
      other neuropsychiatric disorders. Agents in this heterogeneous group of compounds
      are generally better tolerated and less toxic than the tricyclic antidepressants
      (TCAs), which they have in many respects superseded. This review summarizes
      available data on paroxetine, the newest SSRI to receive approval for the
      treatment of depression.

PMID- 8252847
TI  - Rhabdomyolysis and renal failure secondary to combination therapy of
      hyperlipidemia with lovastatin and gemfibozil.

PMID- 8252848
TI  - Guidelines for management of patients with methicillin-resistant Staphylococcus
      aureus in acute care hospitals and long-term care facilities. The MRSA
      Interagency Advisory Committee in conjunction with the Connecticut Department of
      Public Health and Addiction Services, July 1993.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium that can
      colonize or infect people. MRSA strains are not more virulent than methicillin
      susceptible strains. Colonized and infected patients represent the most important
      reservoir of MRSA in hospitals. MRSA is transmitted by direct person-to-person
      contact, usually on the hands of health care workers. Limiting the spread of MRSA
      is desirable because the organism is resistant to oxacillin, nafcillin,
      cephalosporins, and imipenem. Treatment of choice for MRSA infection is usually
      intravenous vancomycin. The preferred methods for antimicrobial susceptibility
      testing of S. aureus include oxacillin-salt screening plates, microdilution broth
      tests with 2% NaCI, and disk diffusion tests incubated for 24 hours at 35 degrees
      C. Hospitals and LTCFs should monitor the incidence of nosocomial transmission of
      MRSA in their facility. Hospital admission because of MRSA infection is
      acceptable medical practice because treatment can best be accomplished in an
      acute care setting. However, given special circumstances, treatment of MRSA
      infection can be accomplished in an extended care facility or at home. This
      decision is based on the clinical judgement of the attending physician. Hospital
      admission solely because of MRSA colonization is unwarranted. MRSA colonization
      is not a contraindication to discharge from an acute care hospital to home or
      another facility. When a hospitalized patient who is colonized with MRSA no
      longer needs to receive acute nursing care (i.e. their MRSA infection and/or
      other acute medical problems are under control), they can be discharged. If they
      are discharged to another institution, that institution should be notified in
      advance that the patient is colonized with MRSA.

PMID- 8252849
TI  - The medical treatment of hypercalcemia.

PMID- 8252850
TI  - The Connecticut State Medical Society from 1860 to the present.

PMID- 8252851
TI  - Menghini needle.

PMID- 8252852
TI  - Renal physiology and pathophysiology of aging.

PMID- 8252853
TI  - Renal biopsies in the elderly. A 20 years' experience.

PMID- 8252854
TI  - Renal biopsy in the elderly.

PMID- 8252855
TI  - Glomerulonephritis among other causes of referral of elderly patients to a renal
      division. A 20 years' experience.

PMID- 8252856
TI  - Glomerulonephritis in elderly patients.

PMID- 8252857
TI  - Renal biopsy findings in patients older than 65 years of age presenting with the
      nephrotic syndrome. A report from the MRC Glomerulonephritis Registry.

PMID- 8252858
TI  - Ischemic nephropathy in the elderly.

PMID- 8252859
TI  - Light chain deposition nephropathy in multiple myeloma.

PMID- 8252860
TI  - Treatment of idiopathic glomerulonephritis in the elderly. Personal data.

PMID- 8252861
TI  - Micropolyarteritis and extracapillary/necrotizing glomerulonephritis in the
      elderly.

PMID- 8252862
TI  - Renal histological findings in elderly adults over 75 years of age.

PMID- 8252863
TI  - IgA mesangial nephropathy in over-75-year-old patients.

PMID- 8252864
TI  - Nephropathies in the elderly. An epidemiological study.

PMID- 8252865
TI  - Epidemiology of primary glomerular disease in the elderly. A prospective study
      during a 15-year period.

PMID- 8252866
TI  - Chronic renal failure due to atheromatous renovascular disease in the elderly.

PMID- 8252867
TI  - Treatment of the nephritic syndrome in elderly with human intravenous
      immunoglobulins.

PMID- 8252868
TI  - Proteinuria as a function of hypertension and age.

PMID- 8252869
TI  - Primary nephrotic syndrome in the elderly.

PMID- 8252870
TI  - Idiopathic glomerulonephritis in the elderly.

PMID- 8252871
TI  - Treatment and clinical outcome of glomerulonephritis in the elderly.

PMID- 8252872
TI  - Nephrotic syndrome in the elderly. A retrospective study in steroid-treated
      patients.

PMID- 8252873
TI  - Idiopathic membranous glomerulonephritis in the elderly.

PMID- 8252874
TI  - Outcome of membranous glomerulonephritis in the elderly.

PMID- 8252875
TI  - Changing pattern of glomerulonephritis in the elderly: a change of prevalence or
      a different approach?

PMID- 8252876
TI  - Renal tubular function in the elderly.

PMID- 8252877
TI  - Glomerulonephritis in the elderly aged over 65. Clinicopathological analysis of
      92 patients.

PMID- 8252878
TI  - Contrasting clinical course of Henoch-Schonlein purpura in younger and elderly
      patients.

PMID- 8252879
TI  - Rapidly progressive glomerulonephritis in the elderly. Long-term results.

PMID- 8252880
TI  - Out-of-hospital cardiac arrest: an argument for aggressive therapy for both
      ventricular tachyarrhythmias and nonventricular tachyarrhythmias.

PMID- 8252881
TI  - Gastric lesions in neonates: effects of stress?

PMID- 8252882
TI  - Predicting outcome from sepsis.

PMID- 8252883
TI  - Knowing the pattern: does it help in patient care?

PMID- 8252884
TI  - Acidosis, epinephrine, and the model.

PMID- 8252885
TI  - Compression-assisted expiration in asthma.

PMID- 8252886
TI  - A novel leukotriene B4-receptor antagonist in endotoxin shock: a prospective,
      controlled trial in a porcine model.
AB  - OBJECTIVE: To evaluate the hypothesis that treatment with LY255283, a novel
      leukotriene B4-receptor antagonist, is beneficial in an animal model of the adult
      respiratory distress syndrome induced by endotoxin. DESIGN: Prospective,
      randomized, controlled trial. SETTING: Laboratory at a large university medical
      center. SUBJECTS: Twenty-five, immature, random-bred swine. INTERVENTIONS: Four
      groups of pigs were studied: the LPS group of animals (n = 6) were infused with
      Escherichia coli lipopolysaccharide (strain 0111:B4, 250 micrograms/kg) from 0 to
      60 mins; the LPS + 255283 group of animals (n = 6) were infused with
      lipopolysaccharide as above, but were also treated with LY255283 (30 mg/kg, then
      10 mg/kg/hr), beginning at -15 mins; the 255283 group of animals (n = 6) were
      infused with the same dose of LY255283, but were not challenged with
      lipopolysaccharide; and the RL control group of subjects (n = 7) received only
      the lactated Ringer's solution vehicle. Beginning at 30 mins, all groups were
      infused with dextran-70 solution as needed to maintain cardiac output at 90% to
      110% of baseline value. MEASUREMENTS AND MAIN RESULTS: Treatment with LY255283
      significantly (p < .05) ameliorated lipopolysaccharide-induced systemic arterial
      hypotension, pulmonary arterial hypertension, and arterial hypoxemia. Treatment
      with this drug also abrogated lipopolysaccharide-induced increases in pulmonary
      extravascular water content and bronchoalveolar lavage fluid protein
      concentration. CONCLUSIONS: These data suggest that leukotriene B4 may be an
      important mediator of acute lung injury in this porcine model of septic shock and
      acute lung injury. Further studies to assess the specificity of LY255283 as a
      leukotriene B4 antagonist are necessary in order to exclude the possibility that
      the beneficial effects of this compound are due to pharmacologic actions other
      than the blockade of LTB4 receptors.

PMID- 8252887
TI  - Cardiac arrest presenting with rhythms other than ventricular fibrillation:
      contribution of resuscitative efforts toward total survivorship.
AB  - OBJECTIVE: The medical literature portrays a bleak prognosis for out-of-hospital
      cardiac arrest cases presenting with asystole, idioventricular rhythms with
      pulselessness, or primary electromechanical dissociation. In view of evolving
      philosophies to waive resuscitation attempts in such cases, we sought to
      delineate the actual contribution toward overall survivorship that is provided by
      resuscitation efforts for patients who have these electrocardiographic
      presentations. DESIGN: A prospective outcome study which analyzed all out-of
      hospital cardiac arrest cases in a large city for a 2-yr period in terms of
      presenting electrocardiogram, age, sex, presence and status of witnesses,
      performance of bystander cardiopulmonary resuscitation, and survival to
      successful hospital discharge. SETTING: A large urban municipality (population,
      two million) served by a single, centralized emergency medical services program.
      PATIENTS: Excluding cases associated with trauma, drugs, airway obstruction,
      submersion or primary respiratory illness, 2,404 consecutive adult out-of
      hospital cardiac arrest patients were studied. INTERVENTIONS: Standard advanced
      cardiac life support. MEASUREMENTS AND MAIN RESULTS: Although survival "rates" of
      patients with asystole, idioventricular rhythms with pulselessness, and
      electromechanical dissociation were low (1.6%, 4.7% and 6.9%, respectively),
      22.2% of the 193 total survivors (confidence interval: +5.9%) initially presented
      with one of these electrocardiographic rhythms (14 asystole, 18 idioventricular
      rhythms with pulselessness, 10 electromechanical dissociation, plus one other).
      CONCLUSIONS: Despite poor survival "rates," resuscitative efforts for patients
      presenting with asystole, electromechanical dissociation, and idioventricular
      rhythms with pulselessness all contribute significantly toward a community's
      total survivorship from out-of-hospital cardiac arrest. Initial, aggressive
      attempts at resuscitation still should be emphasized in such patients.

PMID- 8252888
TI  - Impact of multiple risk factors and ranitidine prophylaxis on the development of
      stress-related upper gastrointestinal bleeding: a prospective, multicenter,
      double-blind, randomized trial. The Ranitidine Head Injury Study Group.
AB  - OBJECTIVES: To evaluate the impact of risk factors on the development of stress
      related upper gastrointestinal bleeding in severe head injury patients randomized
      to treatment with a 6.25 mg/hr continuous ranitidine infusion or placebo. DESIGN:
      Prospective, multicenter, randomized, double-blind, placebo-controlled, parallel
      group study. SETTING: Ten intensive care units in the United States. PATIENTS:
      Patients with severe head injury, defined as having a Glasgow Coma Score of < or
      = 10, were eligible for enrollment. INTERVENTIONS: Ranitidine 6.25 mg/hr or
      saline placebo was administered by continuous infusion for a maximum of 5 days.
      MEASUREMENTS AND MAIN RESULTS: Patients were evaluated every 8 hrs for the
      presence of stress-related upper gastrointestinal bleeding. Bleeding developed in
      15 (19%) of 81 placebo-treated patients vs. three (3%) of 86 ranitidine-treated
      patients (p = .002). None of the individual risk factors had a significant effect
      on bleeding frequency. No bleeding occurred in the four patients with one risk
      factor. Placebo bleeding rates in patients with 2, 3 to 5, and > 5 risk factors
      were 20%, 20%, and 18%, respectively. For the ranitidine-treated patients,
      bleeding was reported in 0%, 5%, and 0% in the 2, 3 to 5, and > 5 risk factor
      subgroups, respectively. Pneumonia occurred in 19% of the placebo-treated
      patients vs. 14% in the ranitidine treatment group. CONCLUSIONS: The full risk to
      develop stress-related upper gastrointestinal bleeding was realized when two risk
      factors were present concomitantly. The presence of additional risk factors did
      not increase the occurrence of bleeding. A continuous infusion of ranitidine at
      6.25 mg/hr provided significant protection from bleeding, regardless of the
      number of risk factors present.

PMID- 8252889
TI  - Control and variability of gastric pH in critically ill children.
AB  - OBJECTIVES: To determine the effect of illness severity and acute central nervous
      system injury on the control and variability of gastric pH in pediatric intensive
      care unit (ICU) patients receiving ranitidine. DESIGN: Prospective, descriptive
      study. SETTING: Pediatric ICU of a children's hospital. PATIENTS: Fourteen
      pediatric ICU patients. INTERVENTIONS: Ranitidine (4 mg/kg/day) was administered
      to all patients. MEASUREMENTS AND MAIN RESULTS: Patients enrolled in the study
      were divided into two groups based on illness type and severity. Illness severity
      was measured by the Pediatric Risk of Mortality (PRISM) score, with a PRISM score
      of > or = 20 defining severe illness. Illness type was designated as central
      nervous system or noncentral nervous system. Gastric pH was continuously
      monitored in all patients using an intragastric, pH-sensitive electrode. Poor
      control of gastric pH was defined as a pH of < 4.0 for > 20% of the time
      monitored. The statistical significance of the differences between groups was
      measured using the Wilcoxon two-sample test or Fisher's exact test. Patients with
      severe illness or acute central nervous system injury had a lower mean gastric pH
      than all other patients (4.6 vs. 6.4; p = .008) and spent more time with a
      gastric pH of < 4.0 than other patients (47.5% of time monitored vs. 12.5% of
      time monitored; p = .003). Poor control of gastric pH occurred in 100% of
      patients with severe illness or acute central nervous system injury, while only
      20% of the remaining patients had poor control of gastric pH (p = .01). Using
      power-spectrum analysis to evaluate gastric pH variability, gastric pH in
      patients receiving bolus ranitidine was more variable than gastric pH in patients
      receiving ranitidine continuously (p = .045). Illness severity or type had no
      effect on gastric pH variability (p = .78). CONCLUSIONS: a) Continuous infusion
      of ranitidine decreases variability of gastric pH in pediatric ICU patients; b)
      gastric pH variability may make intermittent monitoring of gastric pH inaccurate;
      c) children with acute central nervous system injury or PRISM scores of > or = 20
      have poor control of gastric pH; d) type of injury and PRISM scores predict
      response to ranitidine therapy.

PMID- 8252890
TI  - Occurrence of nosocomial pneumonia in mechanically ventilated trauma patients: a
      comparison of sucralfate and ranitidine.
AB  - OBJECTIVE: To determine if there is a difference in nosocomial pneumonia
      frequency rate in mechanically ventilated trauma patients treated with sucralfate
      vs. ranitidine for stress ulcer prophylaxis. DESIGN: Prospective, randomized
      trial. SETTING: A 640-bed urban teaching hospital and trauma center. PATIENTS:
      Ninety-two mechanically ventilated trauma patients. INTERVENTIONS: Thirty-nine
      patients received sucralfate and 44 patients received intravenous ranitidine for
      stress ulcer prophylaxis; nine patients were excluded from the study for protocol
      breaks. MEASUREMENTS AND MAIN RESULTS: The study population was severely injured
      and critically ill. The Trauma Score averaged 11.3, the Injury Severity Score
      averaged 27.7, and the Acute Physiology and Chronic Health Evaluation (APACHE)
      score averaged 18.1. There were no significant differences in demographics,
      mechanisms of injury, Trauma Score, Injury Severity Score, APACHE score, length
      of hospital stay, length of surgical intensive care unit stay, or duration of
      endotracheal intubation between the sucralfate and ranitidine groups. Eleven
      (13.2%) patients developed nosocomial pneumonia: six (15.4%) of 39 patients in
      the sucralfate group and five (11.4%) of 44 patients in the ranitidine group;
      these numbers were not significantly different (chi 2 = 0.0226, p = .8805). There
      were no episodes of significant upper gastrointestinal bleeding. Six patients
      died during hospitalization, all secondary to severe head injury and none with
      pneumonia. CONCLUSIONS: There was no statistically significant difference in
      pneumonia rate in mechanically ventilated trauma patients receiving stress ulcer
      prophylaxis with sucralfate vs. ranitidine.

PMID- 8252891
TI  - High prevalence of asymptomatic esophageal and gastric lesions in preterm infants
      in intensive care.
AB  - OBJECTIVE: To establish the prevalence of upper gastrointestinal mucosal lesions
      in full-term and preterm infants under stress. DESIGN: A prospective, cohort
      study. SETTING: Neonatal intensive care unit at a university teaching hospital.
      PATIENTS: Seventeen (14 preterm, 3 term; median gestational age 29.7 wks; median
      birth weight 1230 g) consecutive, unselected infants treated in intensive care.
      INTERVENTIONS: Gastroscopy, using a prototype fiberoptic gastroscope designed for
      newborns, was performed for the first time at the age of 3 to 7 days. Biopsy
      specimens were taken when possible. Ranitidine treatment and follow-up
      endoscopies were performed in selected patients. Blood pressure, heart rate,
      oxygen saturation by pulse oximeter, and the general condition of the infants
      were monitored at 1-min intervals during the endoscopy. Central nervous system
      ultrasonography examination was repeatedly performed before and after the
      procedure. MEASUREMENTS AND MAIN RESULTS: At the time of first endoscopy, 15 of
      17 infants were asymptomatic for gastrointestinal tract problems, one had melena,
      and one hematemesis. Upper gastrointestinal endoscopy revealed pathology in 16
      (94%) infants, macroscopic esophagitis in six infants, hemorrhagic gastritis in
      nine infants, and gastritis with ulcers in six infants. Microscopically, the
      lesions were also clear. A peculiar finding was acute gastritis with cystic gland
      deformation ("cystic gastritis") seen in five of the infants under stress; one of
      these infants also had intestinal metaplasia in the gastric mucosa. Seven infants
      were treated with ranitidine without side-effects. Follow-up endoscopies
      demonstrated normalization of the lesions in five of six infants studied. The
      procedure, including biopsies, seemed to be safe, even for very low-birth weight
      infants. CONCLUSIONS: Gastric mucosal lesions are highly prevalent in preterm
      infants in intensive care before any symptoms occur. Further research on preterm
      infants under stress is needed in order to determine the risk factors and optimal
      treatment for the esophageal and gastric mucosal lesions described here.

PMID- 8252892
TI  - Prognostic value of the dobutamine test in patients with sepsis syndrome and
      normal lactate values: a prospective, multicenter study.
AB  - OBJECTIVES: To determine the oxygen supply (DO2) and uptake (VO2) responses to a
      60-min dobutamine infusion in critically ill septic patients without circulatory
      shock and with normal blood lactate concentrations. Also, to determine whether
      these responses would predict outcome. DESIGN: Prospective, cohort study.
      SETTING: Five intensive care units in university-affiliated, city hospitals.
      PATIENTS: Fifty critically ill patients with sepsis syndrome were studied from
      April 1990 to August 1991. INTERVENTIONS: Pulmonary artery catheterization; fluid
      loading if pulmonary artery occlusion pressure was < 10 mm Hg; and 10
      micrograms/min/kg dobutamine infusion for 60 mins. MEASUREMENTS AND MAIN RESULTS:
      Cardiac index, DO2, VO2, and oxygen extraction ratio were determined immediately
      before and 1 hr after the onset of the dobutamine test. Using receiver operating
      characteristic curves, responders to the dobutamine infusion were identified by a
      > 15% increase in VO2 from the time immediately before to 1 hr after the onset of
      the dobutamine test. We identified 23 responders and 27 nonresponders. Groups
      differed significantly in age (responders 46 yrs vs. nonresponders 55 yrs) and
      associated chronic disease (responders one cancer vs. nonresponders six cancers).
      Significant changes in responders were: a) cardiac index increased 42.9%; b)
      systemic vascular resistance decreased 20.7%; and c) DO2 increased 39.1% while
      VO2 increased 40.8%, with no changes in oxygen extraction or blood lactate
      concentration. Significant changes in nonresponders were: a) cardiac index
      increased 14.2%; b) DO2 increased 13.2% and c) oxygen extraction decreased from
      0.26 to 0.22. Lactate concentration increased significantly by 25.1% in
      nonresponders. The mortality rate in responders (8.7%) was significantly less
      than that rate in nonresponders (44.4%). CONCLUSIONS: Most of these septic
      patients without shock or hyperlactatemia responded to dobutamine infusion in one
      of two ways: with little increase in DO2 and no increase in VO2, or with
      significant increases in both DO2 and VO2. The latter response is typical of
      healthy volunteers given dobutamine. Because of the calorigenic effect of
      dobutamine, our results imply nothing about the presence or absence of oxygen
      supply limitation. Still, patients who had increases in DO2 and VO2 had a much
      higher survival rate than patients who did not. We speculate that the inability
      of some patients to respond to dobutamine and the associated higher mortality
      rate may be related to beta-adrenoreceptor dysfunction.

PMID- 8252893
TI  - Sequence of physiologic patterns in surgical septic shock.
AB  - OBJECTIVES: Gradual, almost imperceptible transitions occur between localized
      infection, generalized infection, systemic manifestations of the sepsis syndrome,
      septic shock, and death. The aim of this study was to describe the sequential
      pattern of hemodynamic and oxygen transport patterns of survivors and
      nonsurvivors of septic shock, so as to differentiate primary from secondary and
      tertiary events, to evaluate possible physiologic mechanisms, and to provide a
      template to relate the appearance of biochemical mediators to the sequence of
      physiologic events. DESIGN: Prospective, cohort study. SETTING: University-run
      county hospital. PATIENTS: A series of 300 consecutive surgical patients with
      septic shock; 85 survived and 215 died. INTERVENTIONS: We used specific criteria
      to define stages as: a) early period, the first recorded increase in cardiac
      output; b) middle period, time of maximal metabolic activity defined as the
      highest recorded oxygen consumption (VO2); and c) late period, the time of death
      or recovery. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport
      variables were measured at frequent intervals throughout the course of septic
      shock. Beginning with increased cardiac index and oxygen delivery (Do2), which
      were the earliest observed hemodynamic changes, there were progressive increases
      in cardiac index, DO2, and VO2. The values of these variables in the survivors
      were both greater than normal and greater than those values of the nonsurvivors
      at comparable time periods. These values decreased in the late stage in
      nonsurvivors. There were early transient reductions in VO2 that preceded the
      increase in temperature and the decrease in blood pressure in both survivors and
      nonsurvivors. Although 86% of the septic patients were hyperdynamic, there were
      transient hypodynamic episodes (defined as cardiac index < 2.5 L/min/m2) in < 10%
      of the measurements. Transient preterminal hypermetabolic periods occurred in 9%
      of the nonsurvivors. CONCLUSIONS: Increased cardiac index and DO2 represent
      compensations for circulatory deficiencies that limit body metabolism, as
      reflected by inadequate VO2. Survivors have higher cardiac index, DO2, and VO2
      values than those values of both the nonsurvivors and normal values. These data
      suggest that therapy should be directed toward increasing cardiac index to > 5.5
      L/min/m2, DO2 to > 1000 mL/min/m2, and VO2 to > 190 mL/min/m2 as therapeutic
      goals; these supranormal values were empirically determined by the patterns of
      the survivors. Further studies to describe temporal relationships of biochemical
      mediators of these physiologic patterns are needed.

PMID- 8252894
TI  - Outcomes of children in a persistent vegetative state.
AB  - OBJECTIVE: To determine the long-term outcomes and resource utilization of
      children discharged home in a vegetative state following neurologic injury.
      DESIGN: A case series. SETTING: Patients' homes. PATIENTS: Twenty children
      discharged from acute and chronic care hospitals with a diagnosis and discharge
      examination consistent with the vegetative state. INTERVENTIONS: Home care
      delivered, in part, by registered nurses. MEASUREMENTS: Assessed outcomes
      included survival/death, mental status, functional status, costs, and personnel
      requirements and technologies used for home care. A mailed questionnaire and
      telephone follow-up were used to assess patients awareness and caretaker
      satisfaction with home care. RESULTS: Children were followed in the vegetative
      state for 4.5 +/- 2.9 yrs. Six children died at home and two children died after
      rehospitalization. Twelve children survived at home, all for > 1 yr; eight
      children survived for > 3 yrs. Most patients were stable after the first year of
      home care. Twelve of 13 caretakers felt their child had some minimal awareness
      (e.g., voice recognition), although all children remained totally dependent.
      Costs of care averaged > $90,000/yr per patient. Care included 10 to 12 hrs/day
      of professional nursing care, and extensive time investments by other personnel,
      including public school personnel. CONCLUSIONS: The long-term outcome for
      children discharged from the hospital in a persistent vegetative state was poor.
      Forty percent of the patients died and, at best, children showed only minimal
      awareness after an average of 4.5 yrs. Care costs were > $90,000/yr per patient.

PMID- 8252895
TI  - Respiratory deadspace measurements in neonates during extracorporeal membrane
      oxygenation.
AB  - OBJECTIVES: To evaluate the bias and precision of a simple, bedside method of
      quantification of minute CO2 production (study 1) and then apply the technique to
      measure physiologic deadspace in a group of neonates undergoing extracorporeal
      membrane oxygenation (ECMO) (study 2). DESIGN: A prospective, clinical study
      comparing a simple method of quantifying minute CO2 production with a criterion
      standard (study 1); a cohort study evaluating the utility of deadspace
      measurements in neonates undergoing extracorporeal membrane oxygenation (study
      2). SETTING: Tertiary care pediatric intensive care unit (ICU) in a university
      hospital. PATIENTS: Study 1: Thirteen neonates (weighing from 2.5 to 6.2 kg) were
      studied during mechanical ventilation being administered for a variety of
      respiratory diseases. Study 2: Fifteen neonates with respiratory failure were
      examined during the course of ECMO. INTERVENTIONS (METHODS): Study 1: The CO2
      concentration of expired gas sampled at the exhaust port of the test ventilator
      was continuously measured and transformed to minute CO2 production by the
      following formula: (calculated minute CO2 production) = (tension of CO2 in
      exhaust gas) x 0.0013 x (ventilator pneumotachometer minute volume), where 0.0013
      is the conversion factor to express gas tension as fractional volume at standard
      conditions. Minute CO2 production was measured independently with a previously
      validated bedside calorimeter and the calculated and measured values were
      compared. Study 2: The CO2 concentration of expired gas sampled at the exhaust
      port of the test ventilator was continuously measured and transformed to mixed
      expired CO2 by the following formula, which corrects for compressible volume
      measured by the ventilator pneumotachometer: mixed expired CO2 = (tension of CO2
      in exhaust gas) x (ventilator pneumotachometer minute volume)/(minute volume at
      proximal airway). We then utilized the Bohr-Enghoff method to calculate the
      deadspace/tidal volume ratio: deadspace/tidal volume ratio = (PaCO2--mixed
      expired CO2 tension)/PaCO2. MEASUREMENTS AND MAIN RESULTS: Study 1: Calculated
      minute CO2 production ranged between 11.8 and 38.9 mL/min. When compared with
      measured minute CO2 production, the bias and precision were -0.8 and 1.7 mL/min,
      respectively. The mean percent difference for calculated minute CO2 production
      was 3.7%. Study 2: Deadspace/tidal volume ratio was calculated during temporary
      separation from ECMO support as the patients demonstrated improvements in gas
      exchange and lung compliance. Fifty-two measurements were made in 15 patients,
      and 13 of 15 patients demonstrated a decrease in deadspace/tidal volume ratio
      during the course of ECMO. The mean decrease was 21% and the decrease was
      statistically significant. CONCLUSIONS: Minute CO2 production can be measured
      simply and accurately, using equipment readily available in most ICU settings.
      The same method can be utilized to calculate the deadspace/tidal volume ratio,
      which provides valuable information regarding the gas exchanging efficiency of
      the neonatal lung during ECMO.

PMID- 8252896
TI  - Metabolic acidemia with hypoxia attenuates the hemodynamic responses to
      epinephrine during resuscitation in lambs.
AB  - OBJECTIVE: To examine the effects of metabolic acidemia and hypoxia on the
      hemodynamic responses to epinephrine in an intact neonatal animal model. DESIGN:
      Multi-experiment, randomized, controlled trial. SETTING: Animal research
      laboratory of a university hospital. SUBJECTS: Sixteen lambs, ranging in age from
      2 to 14 days. INTERVENTIONS: The lambs were chronically catheterized; the ductus
      arteriosus was ligated; and a pulmonary arterial flow probe was inserted to
      measure cardiac output, blood pressure (BP), and heart rate. In the first
      protocol, hemodynamic responses to epinephrine during pure metabolic acidemia or
      metabolic alkalosis were studied in eight lambs. Each lamb was studied on four
      different days at a different arterial pH: 6.9, 7.1, 7.4, and 7.6. Ventilation
      was controlled to maintain PCO2 at 35 to 45 torr (4.66 to 5.99 kPa). Acidemia was
      induced by the infusion of lactic acid and alkalosis by the infusion of sodium
      bicarbonate. When the appropriate arterial pH was achieved, 10 micrograms/kg of
      epinephrine was administered intravenously. In a second protocol, hemodynamic
      responses to epinephrine during metabolic acidemia or alkalosis plus hypoxia were
      studied in eight lambs. When the appropriate arterial pH was achieved, hypoxia
      was induced until cardiac output decreased to 40% of baseline. Epinephrine bolus
      was given, and after 90 secs, the lambs were resuscitated with oxygen.
      MEASUREMENTS AND MAIN RESULTS: Epinephrine administered during uncompromised
      hemodynamics led to hypertension, bradycardia, and decreased cardiac output that
      were unaffected by arterial pH values between 6.9 and 7.6. Acidemia with hypoxia
      compromised hemodynamics with decreases in heart rate and cardiac output.
      Epinephrine administered during this compromised condition did not improve
      cardiac output, heart rate, or BP before resuscitation with oxygen at any
      arterial pH studied. Resuscitation with epinephrine and oxygen during
      hemodynamically compromised states led to increases in heart rate, BP, and
      cardiac output with significant attenuation of these hemodynamic responses during
      metabolic acidemia at pH values of 6.9 and 7.1. CONCLUSIONS: During the
      physiologic conditions associated with neonatal resuscitation, that is, hypoxia
      with a compromised hemodynamic state, metabolic acidemia significantly attenuates
      the hemodynamic responses to resuscitation with epinephrine and oxygen.
      Correction of metabolic acidosis may be warranted in newborn resuscitation.

PMID- 8252897
TI  - Cardiorespiratory consequences of expiratory chest wall compression during
      mechanical ventilation and severe hyperinflation.
AB  - OBJECTIVES: To measure and compare the effects of manual expiratory compression
      of either the rib cage or abdomen on cardiac output, end-expiratory lung volume,
      and other cardiorespiratory variables in an animal model that mimics the severe
      pulmonary hyperinflation and hemodynamic impairment occurring in patients with
      severe acute asthma during mechanical ventilation. DESIGN: Prospective,
      randomized, crossover trial. SETTING: Research laboratory. SUBJECTS: Seven cross
      bred, anesthetized, supine dogs. INTERVENTIONS: The following sequence was
      employed: a) spontaneous breathing without pulmonary hyperinflation; b) positive
      pressure ventilation with severe pulmonary hyperinflation (produced by an
      external variable expiratory flow resistor); c) approximately 7 mins of manual
      expiratory compression of either the rib cage or abdomen during positive-pressure
      ventilation-hyperinflation. This sequence was then repeated, incorporating the
      alternative type of expiratory compression. MEASUREMENTS AND MAIN RESULTS:
      Cardiac output (measured by thermodilution), aortic pressure, pleural
      (esophageal) pressure, and changes in end-expiratory lung volume were measured.
      The decrease in cardiac output due to mechanical ventilation with pulmonary
      hyperinflation was exacerbated by rib cage compression (p < .001; spontaneous
      breathing 2.9 +/- 0.2 L/min, hyperinflation 1.5 +/- 0.1 L/min, and rib cage
      compression 1.0 +/- 0.1 [SEM] L/min). However, the positive-pressure ventilation
      hyperinflation-induced decrease in cardiac output was attenuated by abdominal
      compression (p < .001; spontaneous breathing 3.3 +/- 0.2 L/min, hyperinflation
      1.4 +/- 0.1 L/min, and abdominal compression 2.1 +/- 0.1 L/min). Mean aortic
      pressure returned to prehyperinflation levels during abdominal compression (p <
      .001; spontaneous breathing 126 +/- 2 mm Hg, hyperinflation 75 +/- 5 mm Hg, and
      abdominal compression 120 +/- 3 mm Hg). Both types of compression were similarly
      effective (p > .75) in increasing mean expiratory pleural pressure, so that end
      expiratory lung volume was similarly (p > .25) reduced (0.45 +/- 0.05 and 0.40 +/
      0.05 L for rib cage and abdominal compressions, respectively) in this non-air
      flow, limiting animal model. CONCLUSIONS: The cardiorespiratory effects of
      manually compressing the rib cage or abdomen during expiration in this animal
      study suggest that these techniques should be carefully evaluated in mechanically
      ventilated patients with severe acute asthma.

PMID- 8252898
TI  - Central contribution to hypoventilation during severe inspiratory resistive
      loads.
AB  - OBJECTIVE: Recent observations suggest that central hypoventilation with slowing
      of respiratory frequency contributes to hypoventilation during severe inspiratory
      resistive loads. We carried out a study to further characterize this bradypneic
      response. DESIGN: Prospective, controlled laboratory study. SETTING: Basic
      science laboratory of a university hospital. SUBJECTS: Anesthetized adult cats
      (loading experiment n = 7, nonloaded hypercapnic controls n = 11). INTERVENTIONS:
      Experimental inspiratory loads increased transdiaphragmatic pressure to 75% of
      the maximum for each animal. Respiratory responses were observed at midrun or
      moderate conditions of respiratory insufficiency (defined as PaCO2 > or = 60 torr
      [> or = 8.0 kPa]) and failure (PaCO2 > or = 80 torr [> or = 10.6 kPa]). Nonloaded
      hypercapnic controls were studied with similar durations of exposure to CO2 in
      the same CO2 range. MEASUREMENTS: Inspiratory airflow, tidal volume, respiratory
      frequency, airway pressure, transdiaphragmatic pressure, transdiaphragmatic
      pressure response to phrenic nerve electrical stimulation, blood gas analysis.
      Severe inspiratory loads were applied to anesthetized adult cats to determine
      whether bradypnea could be observed in an anesthesized model that eliminated
      conscious responses. Experiments were performed in hyperoxic conditions to
      determine whether bradypnea develops in the absence of hypoxia. An additional
      control group was studied under hypercapnic conditions without loading to
      determine whether comparable hypercapnia is a sufficient stimulus to elicit
      bradypnea. RESULTS: From midrun until failure, minute ventilation decreased by
      16% in loaded animals. Hypoventilation was associated with a decrease in
      respiratory frequency from 40.1 to 29.9 breaths/min, whereas tidal volume,
      spontaneous transdiaphragmatic pressure, and transdiaphragmatic pressure response
      to phrenic nerve electrical stimulation remained unchanged. Control animals had
      no significant reduction in ventilation or respiratory frequency over similar
      levels and durations of hypercapnia. CONCLUSIONS: Centrally mediated bradypnea
      contributed to hypoventilation in respiratory failure associated with inspiratory
      loading. Bradypnea preceded evidence of muscle fatigue. This change in
      respiratory cycle timing occurred under anesthesia, and thus, did not depend on
      conscious perception of dyspnea. Bradypnea does not depend on either hypercapnia
      or hypoxia.

PMID- 8252899
TI  - Induction of microcurrents in critically ill patients in magnetic resonance
      systems.
AB  - OBJECTIVE: To determine whether electric current can be induced in intracardiac
      catheters, thermistor wires and pacing electrodes in patients during magnetic
      resonance imaging (MRI). DESIGN: Prospective laboratory study. SETTING:
      Postgraduate medical school hospital. SUBJECTS: A sheep heart model.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Voltage generated by saline
      0.9% flowing through a magnetic field and distribution of current from a catheter
      tip within a sheep heart model were measured in a 0.15 Tesla MRI system.
      Resistance of loops formed by pacing wires, a pacing electrode, and a thermistor
      wire were measured in saline 0.9%. Effects of rapidly changing magnetic fields
      and the movement of the beating heart on epicardial pacing wires were calculated
      theoretically. A flow of 200 mL/min of saline 0.9% induced a current of 0.1
      microampere (microA) (at 0.15 Tesla). From magnetic resonance images we derived a
      current density of approximately 0.004 microA/mm2 (at 0.15 Tesla). Internal
      resistance of pacing catheters and thermistor wires was > 1 megaohm (M omega).
      The maximum currents calculated (for a higher field strength of 1.5 Tesla) in a
      circuit formed by epicardial pacing wires were 80 microA, induced by the beating
      heart moving the wires through the magnetic field and 46 microA, induced by the
      rapidly changing magnetic fields. CONCLUSIONS: Current generated by flow of
      conducting fluid should be safe. Pacing catheters and thermistor wires should be
      safe if well insulated and disconnected from external electric connections.
      However, current induced in epicardial pacing wires may be a hazard, and
      precautions should be taken. External wire tips must be separated, insulated, and
      coiled to lie along the axis of the magnetic field. Electrocardiography is
      required, and defibrillation equipment should be available.

PMID- 8252900
TI  - Acute asphyxia affects neutrophil number and function in the rat.
AB  - OBJECTIVES: Previous studies in adults suggest that various types of physiologic
      stress appear to decrease phagocytic cell function. Adherence and chemotaxis of,
      and phagocytosis and bacterial killing by, neonatal neutrophils are altered
      compared with adult neutrophil function. Stresses encountered by the fetus and
      neonate, such as asphyxia, were hypothesized to further alter neonatal neutrophil
      function. To investigate the impact of asphyxia on systemic immunity, we
      developed a rat model of acute asphyxia and evaluated the effect of asphyxia on
      neutrophil number and function. DESIGN: Prospective, laboratory study. SETTING:
      Research laboratory. SUBJECTS: Adult female Wistar rats. INTERVENTIONS: Exposure
      to CO2 and cold stress. MEASUREMENTS AND MAIN RESULTS: Arterial blood gas, blood
      glucose, neutrophil number, neutrophil-mediated, complement-dependent bacterial
      phagocytosis and killing were determined. After a 20-sec exposure to CO2 and cold
      stress (dry ice vapors), adult rats developed acute respiratory acidosis (pH 6.89
      +/- 0.26, PaCO2 220 +/- 183 torr [29.3 +/- 24.3 kPa]), and mild hypoxia (60 +/-
      20 torr [8.0 +/- 2.7 kPa]) followed by significant metabolic acidosis (base
      deficit = -12.0 +/- 1.5). Neutrophil number slowly increased and reached
      statistical significance by 72 hrs (5.0 +/- 1.5 x 10(3)/mm3) compared to controls
      (2.9 +/- 1.6 x 10(3)/mm3) (p = .03). Phagocytosis and killing of group B
      streptococci by neutrophils isolated immediately after asphyxia were
      significantly impaired (p = .03), and this decrease in function lasted for 24 hrs
      after asphyxia (p = .04), as measured by two different in vitro complement and
      antibody-mediated functional assays. CONCLUSIONS: After brief exposure to CO2 and
      cold stress, rats developed an acute respiratory acidosis and subsequent
      metabolic acidosis similar to acute asphyxia. Neutrophil number did not increase
      until 72 hrs after asphyxia. However, neutrophil-mediated phagocytosis and
      killing of bacteria were immediately impaired. We speculate that asphyxia may
      increase the risk for sepsis secondary to altered neutrophil function.

PMID- 8252901
TI  - Relationship of burn-induced lung lipid peroxidation on the degree of injury
      after smoke inhalation and a body burn.
AB  - OBJECTIVE: We compared the effect of a modest smoke inhalation injury, a burn
      injury alone, and a smoke inhalation injury plus a body burn, on the degree of
      lung oxidant-induced lipid peroxidation and lung injury. DESIGN: Prospective
      animal study with concurrent controls. SETTING: An animal laboratory. SUBJECTS:
      Forty-four adult yearling female sheep (weight range 45 to 50 kg). INTERVENTIONS:
      Forty-four sheep were prepared with lung and prefemoral (soft tissue) lymph
      fistulas. Twelve breaths of cooled smoke with tidal volume of 10 mL/kg body
      weight were given to 24 sheep, producing a peak blood carboxyhemoglobin of 25% to
      30%. Twelve sheep also received a 15% total body surface third-degree burn. Sheep
      were killed at 4 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: Circulating lipid
      peroxidation was monitored as conjugated dienes and tracheobronchial mucosal and
      lung parenchyma as malondialdehyde. Antioxidant defenses were monitored by
      catalase activity. Lung physiologic and histologic changes were compared. We
      noted intense airways inflammation in both smoke inhalation groups and lung
      parenchymal inflammation in all groups. Lung lymph flow was modestly increased
      (two-fold) in the smoke inhalation groups. Alveolar water content was not
      significantly increased after any injury. PaO2 was decreased at 24 hrs after the
      smoke insult alone. Parenchymal malondialdehyde content did not increase with the
      smoke insult alone, but did increase from a control value of 110 +/- 20 to 270 +/
      24 nmol/g tissue by 4 hrs in the combined burn and smoke injury group, while
      catalase activity decreased. Airway mucosal malondialdehyde did not increase in
      any group. CONCLUSIONS: We conclude that alveolar capillary permeability is not
      increased early after a moderate smoke injury or smoke injury with burn. Lipid
      peroxidation is not increased in large airway or lung parenchyma with early after
      smoke exposure. The addition of a burn significantly increases lung parenchymal
      lipid peroxidation, but the oxidant changes do not correspond with the degree of
      early lung dysfunction.

PMID- 8252902
TI  - Prognostic and clinical relevance of pupillary responses, intracranial pressure
      monitoring, and brainstem auditory evoked potentials in comatose patients with
      acute supratentorial mass lesions.
AB  - OBJECTIVE: To test the hypothesis that the clinical condition and outcome in
      patients with acute supratentorial mass lesions can be assessed by determination
      of pupillary abnormalities, measurement of intracranial pressure, and results of
      brainstem auditory evoked potentials. DESIGN: Prospective case series of 55
      patients presenting with supratentorial mass lesions. SETTING: Neurologic and
      neurosurgical intensive care unit of a tertiary care center. PATIENTS: Fifty-five
      comatose patients (26 female/29 male; 9 to 70 yrs of age [mean 44]).
      INTERVENTIONS: Pupillary abnormalities were rated "normal," "unilaterally
      enlarged," "unilaterally fixed," and "bilaterally abnormal." The outcome was
      rated using the Glasgow Outcome Scale. Intracranial pressure values were graded
      into five categories. Brainstem auditory evoked potentials were rated
      "bilaterally normal," "unilaterally abnormal," or "bilaterally abnormal,"
      according to normative data. Statistical evaluation was performed by frequency
      analysis (Fisher's exact test, two-tailed) and calculation of contingency
      coefficients. MEASUREMENTS AND MAIN RESULTS: Outcome was poor in 24 patients,
      good in eight patients, and 23 patients were severely disabled. Statistical
      analysis showed prognostic significance of both pupillary abnormalities (p =
      .0000542; contingency coefficient = .589) and increased intracranial pressure (p
      = .0084; contingency coefficient = .352). Brainstem auditory evoked potential
      categories correlated significantly with pupillary abnormalities (p = .000276;
      contingency coefficient = .505) and increased intracranial pressure (p = .0301;
      contingency coefficient = .502) but did not predict outcome (p = .645;
      contingency coefficient = .321). CONCLUSIONS: Pupillary abnormalities may serve
      as a reliable parameter, which may even be superior to brainstem auditory evoked
      potential testing and intracranial pressure monitoring for prediction of outcome
      in comatose individuals with supratentorial mass lesions. Brainstem auditory
      evoked potentials can be used to support the clinical relevance of abnormal
      pupillary status and increased intracranial pressure but are of no prognostic
      value. Increased intracranial pressure is associated with abnormalities in
      pupillary status and brainstem auditory evoked potentials. Examination for
      pupillary abnormalities in combination with intracranial pressure monitoring and
      brainstem auditory evoked potential testing seems to be a useful strategy in
      managing patients with supratentorial mass lesions in critical care units.

PMID- 8252903
TI  - Brain death in the pediatric patient: historical, sociological, medical,
      religious, cultural, legal, and ethical considerations.
AB  - OBJECTIVE: To detail the origins of the definition of death, the development of
      the criterion of whole brain death as fulfilling the definition of death, and the
      tests used to fulfill that criterion. DATA SOURCES: A review of the literature
      was performed. No Institutional Review Board approval was necessary. DATA
      EXTRACTION: In 1959, patients were described as being in "coma depasse" or beyond
      coma. In 1967, the first successful heart transplantation took place, with the
      organ coming from a brain-dead, beating-heart donor. However, anxiety over the
      definitions of death did not begin with the modern, technological era, and death
      itself has never been definable in objective terms. It has always been a
      subjective and value-based construct. During ancient times, most people agreed
      that death occurred when a person's heartbeat and breathing stopped. For the
      Greeks, the heart was the center of life; for the ancient Hebrews and Christians,
      the breath was the center of life. In the 12th century, Maimonides pointed toward
      the head, and the loss thereof, as the reason for lack of central guidance of the
      soul. Physicians neither diagnosed nor certified death. During the Enlightenment,
      the necessity of heartbeat, breath, and consciousness for the definition of life
      was questioned, leading to questioning regarding the definition of death. Tests
      to fulfill the criteria of death, and tests to determine the absence of
      integration between functions of respiration, circulation, and neurology were
      introduced. Sensorimotor potential was becoming recognized as defining life,
      rather than heartbeat and respiration. As new tests were devised to fulfill
      criteria of death, the physician developed a professional monopoly on meeting the
      criteria of brain death. In the modern era, the boundary between life and death
      has been blurred, but the intensive care unit straddles this boundary. We may
      have situations where the patient is alive but in a coma, without functioning
      heart, lungs, kidneys, or gastrointestinal tract, with a transplanted liver, a
      reversed coagulation system, a blocked immune system, and a paralyzed
      musculoskeletal system. DATA SYNTHESIS: A human being is a man, woman, or child
      who is a composite of two intricately related but conceptually distinguishable
      components: the biological entity and the person. Therefore, human beings can
      suffer more than one death: a biological death and decay, and another death.
      Biological death is a cessation of processes of biological synthesis and
      replication, and is an irreversible loss of integration of the biological units.
      The reasons for having criteria for death are to diagnose death and pronounce a
      person dead. Society can then begin to engage in grief, religious rites,
      funerals, and burials, and accept biological death. Wills can be read, property
      distributed, insurance claimed, individuals can remarry, succession can take
      place, and legal proceedings can begin. Also, organ donation can take place,
      which entails difficult ethical decisions. The Harvard criteria of 1968 were
      devised to set forth brain-death criteria with whole brain death in mind.
      Currently, there are several controversies regarding these criteria: a) whether
      they apply to infants and children; b) whether ancillary tests are necessary; c)
      what the intervals of observation and testing are; and d) are there exceptions to
      the whole brain death criteria. Concerning the use of the adult criteria for
      infants and children, most researchers now agree that the adult criteria apply to
      infants and children who are full term and > 7 days of age. Concerning ancillary
      tests, there has been, in our machine- and technology-oriented profession, a
      great deal of emphasis on the different tests and their ability to fulfill the
      criteria of whole brain death. However, clinical examination and the apnea test
      are usually sufficient to fulfill the criteria. Ancillary tests may be desired in
      some cases, and a variety of these tests is available. (ABSTRACT TR

PMID- 8252904
TI  - Critical care fellowship graduates--1994. The Society of Critical Care Medicine.

PMID- 8252905
TI  - Validation of an oximetry catheter system.

PMID- 8252906
TI  - Midazolam pharmacokinetics.

PMID- 8252907
TI  - Hemodynamic consequences of tension pneumothorax.

PMID- 8252908
TI  - Enteral nutrition with gastric decompression.

PMID- 8252909
TI  - Synchronous mechanical ventilation of neonates.

PMID- 8252910
TI  - Synchronous mechanical ventilation of neonates.

PMID- 8252911
TI  - Acute respiratory failure neuropathy: a variant of critical illness
      polyneuropathy.

PMID- 8252912
TI  - The effects of variation of cryopreservation protocols on the immunogenicity of
      allogeneic skin grafts.
AB  - The use of allografts to effect wound closure on full thickness skin injuries is
      limited by unpredictable graft rejection times. If the period of graft take could
      be extended, the use of allografts would reduce the morbidity and mortality
      associated with these wounds. This study evaluated the effects of variation in
      the cryopreservation protocol on the viability and immunogenicity of skin using a
      murine model system. Immunogenicity was assessed by the stimulatory activity of
      C3H (H-2K) skin-derived epidermal cells (EC) in primary one-way EC/lymphocyte
      reactions with BALB/c (H-2d) and CBA (H-2K) responder lymphocytes. Viability was
      determined by measuring tetrazolium reductase activity. The following
      cryopreservation protocols were assessed: freezing at 1, 30, 64, and > 100
      degrees C/min in 10 and 15% (v/v) Me2SO and freezing at 30 degrees C/min in 5 to
      20% (v/v) Me2SO or glycerol. A cryopreservation protocol of 30 degrees C/min in
      15% (v/v) Me2SO proved optimal for murine skin allograft storage and
      immunomodulation. The viability of skin treated by this protocol was maintained
      (78% of fresh skin viability, no significant difference analysis of variance).
      The stimulatory capacity of treated EC for H-2K and H-2d lymphocytes was 5 +/- 4
      and 5 +/- 9% (+/- 95% confidence limits) of fresh EC (100%) activity. Langerhans
      cell numbers in epidermal sheets and EC suspensions did not correlate with the
      stimulatory capacity of fresh and treated EC for allogeneic lymphocytes. A
      functional impairment of Langerhans cell immunostimulatory capacity was
      implied.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8252913
TI  - The effect of a prostaglandin I2 analogue (OP-41483) on energy metabolism in
      liver preservation and its relation to lipid peroxidative reperfusion injury in
      rats.
AB  - The effect of the stable prostacyclin (PGI2) analogue OP-41483 (OP) on liver
      preservation was investigated in the rat liver transplant model. In a 1-week
      survival study, 33 orthotopic liver transplants were performed using Wistar rats.
      In group A, untreated livers were stored with modified UW (mUW) solution at 4
      degrees C. In group B, livers from OP-pretreated donors (2 micrograms/kg, i.v.)
      were stored with mUW solution containing OP (1 microgram/ml) at 4 degrees C.
      After 24 h storage, the donor grafts in each group were transplanted to untreated
      recipients. OP treatment (group B) significantly improved 1-week survival (62.5%,
      10/16, P < 0.01 versus group A; 11.8%, 2/17). For the measurement of adenine
      nucleotides and lipid peroxidation (malondialdehyde, MDA) in liver tissue before
      preservation, after preservation, and 3 h after transplantation, 20 rat livers in
      groups A and B were studied. In both groups, the levels of adenosine triphosphate
      (ATP) declined 6 h after cold preservation, but this degradation of ATP was
      significantly halted at the level of adenosine monophosphate (AMP) in the OP
      treated livers after 24 h of storage. However, OP treatment showed no significant
      difference in the degree of ATP recovery after transplantation. On the other
      hand, OP treatment resulted in suppression of the increase in MDA levels and
      histological amelioration of microcirculatory disturbance 3 h after
      transplantation. Our data suggested that the combined use of the stable PGI2
      analog (OP-41483) and UW solution is beneficial in liver preservation.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8252914
TI  - Survival rate of frozen-thawed bovine IVM/IVF embryos in relation to post-thaw
      exposure time in two cryoprotectants.
AB  - The relationship between post-thaw exposure time in cryoprotectants and the
      viability of in vitro fertilized (IVF)-derived bovine embryos after culture was
      examined. Good- and excellent-quality Day 7 to Day 8 blastocysts and expanded
      blastocysts were frozen by the nonstepwise method using 1.6 M propylene glycol
      (PG) or ethylene glycol (EG) as the cryoprotectant. After the straws were thawed,
      the embryos were kept in the cryoprotectants for 1, 10, or 30 min. Then the
      embryos were placed directly into culture medium and washed three times, followed
      by coculture with cumulus cells. After 48 h of culture, there were no significant
      differences in survival rate among the various exposure times in PG (79-81%) and
      EG (71-75%). After 72 h of culture, there were no significant differences among
      the various exposure times in the fully expanded (PG 76-81%; EG 71-72%), hatching
      (PG 69-74%; EG 58-71%), and hatched blastocyst rates (PG 60-71%; EG 47-65%). Our
      findings suggest that different post-thaw exposure times up to 30 min using PG or
      EG as the cryoprotectant are not harmful to IVF bovine embryos.

PMID- 8252915
TI  - Ca2+ regulation by cryopreserved bull spermatozoa in response to A23187.
AB  - The regulation of intracellular Ca2+ by fresh and cryopreserved bull spermatozoa
      from the same ejaculates (n = 5) was investigated using the fluorescent Ca2+
      indicator, indo-1. Relative internal Ca2+ levels of the spermatozoa were
      monitored for 30 min prior to the addition of phosphate-buffered saline (PBS), 1
      mM Ca2+, the Ca2+ ionophore A23187 (0.1 microM), or Ca2+ + A23187; during the
      additions the levels of intracellular Ca2+ were observed in detail. After these
      additions, changes in internal Ca2+ levels were monitored for 120 min. The
      initial intracellular Ca2+ levels in the cryopreserved spermatozoa were greater
      than those in fresh (1.05 +/- 0.03 vs 0.97 +/- 0.03 Ca2+ units, P = 0.0001). The
      addition of Ca2+ + A23187 induced elevated cellular Ca2+ in both fresh (P =
      0.0177) and cryopreserved spermatozoa (P < or = 0.0588) within 5 s. Ca2+ alone
      did not differ from Ca2+ + A23187 in increasing Ca2+ in cryopreserved spermatozoa
      (P = 0.2225); fresh spermatozoa were slower to respond to exogenous Ca2+ alone (P
      = 0.0438). At the start of the post-treatment 120 min, cryopreserved spermatozoa
      had more internal Ca2+ than the corresponding fresh samples (P < or = 0.0088)
      except for those exposed to both Ca2+ + A23187 (P = 0.2918). All spermatozoa
      increased internal Ca2+ over the post-treatment time except for the cryopreserved
      PBS controls, and these cryopreserved controls differed from the fresh controls
      in accumulation of Ca2+ (P = 0.0620). None of the Ca2+/A23187 treatments induced
      different rates of change in internal Ca2+ over time in fresh cells (P = 0.3142).
      The rate of Ca2+ accumulation by cryopreserved spermatozoa in the presence of
      exogenous Ca2+ exceeded controls (23.12 +/- 6.75 vs 8.11 +/- 6.75, P = 0.0005),
      but A23187, with or without Ca2+, had no effect (P > or = 0.0907). Following Ca2+
      measurements, the viability of the cryopreserved samples was reduced (P < or =
      0.015) in all but the Ca(2+)-treated spermatozoa (P = 0.1474); no viability
      differences were noted for fresh spermatozoa (P > or = 0.2298). The
      cryopreservation process did not affect acrosomal morphology of the indo-1
      exposed spermatozoa (P > or = 0.1147). These data indicate that Ca2+ regulation
      by Ca(2+)- and A23187-challenged bull spermatozoa differs following
      cryopreservation procedures, possibly relating to the reduced fertilization
      capacity of commercially cryopreserved semen.

PMID- 8252916
TI  - A morphological study of cooling rate response in normal and neoplastic human
      liver tissue: cryosurgical implications.
AB  - The process of freezing in normal human livers and in human liver tumors was
      studied by freezing samples of these tissues with constant cooling rates and then
      examining the morphology of the frozen tissue, after freeze substitution, with
      the light microscope. Cooling rates varied from 2 degrees C/min up to
      approximately 2000 degrees C/min. It was observed that high cooling rates produce
      extensive intracellular ice in both normal and neoplastic liver. At slow rates of
      cooling, normal and neoplastic liver cells dehydrated and large extracellular ice
      crystals formed. Comparison of the frozen normal liver and the frozen malignant
      tumors shows that for the same rates of freezing, the tumor cells retain more
      cellular water and therefore show less susceptibility to dehydration at low rates
      of cooling. At slow cooling rates, the amount of cellular dehydration and
      consequent vascular and interstitial space engorgement changed with the type of
      tissue frozen. The greatest amount of dehydration occurred in normal human liver,
      followed by metastatic colon carcinoma and finally primary hepatocellular
      carcinoma. These results are important for cryosurgery since they suggest that
      malignant tissues have a different response to freezing than normal tissues.

PMID- 8252917
TI  - Control of thermal runaway and uniformity of heating in the electromagnetic
      rewarming of a cryopreserved kidney phantom.
AB  - Successful cryopreservation of whole organs may require electromagnetic (EM)
      heating at much faster warming rates than those at which thermal relaxation can
      smooth out nonuniform power distribution or suppress hot spots which become
      unstable due to an increase of power absorbtion with temperature in the material
      being heated. Calculations of the heating distribution for a uniform spherical
      workpiece in a resonant EM applicator show that the size of a workpiece for which
      there will be good uniformity of heating has a sharp upper limit given D < or =
      0.3 lambda m, where D is the workpiece diameter and lambda m is the EM wavelength
      in the material. We also introduce three stability factors which indicate whether
      thermal runaway can occur; they are dependent solely on the material's dielectric
      properties and the geometry and orientation of any irregularities. These factors
      provide clear guidelines to the choice of source frequency and applicator
      geometry that are favorable for intrinsic control of thermal runaway.
      Experimental results are presented for spherical phantom workpieces of 36- and 45
      mm diameter, rewarmed from -90 to above 0 degrees C in 30 to 150 s, in a 434-MHz
      resonant cavity applicator. The observed spatial temperature distributions for
      different E-field configurations clearly indicate the effectiveness of the
      stability factors in predicting uniformity of temperature, and the significance
      of the workpiece size limit, in practical EM heating situations.

PMID- 8252918
TI  - Protection of freeze-dried Escherichia coli by trehalose upon exposure to
      environmental conditions.
AB  - Freeze-dried cultures of wild-type and genetically engineered strains of
      Escherichia coli lost their colony-forming ability upon exposure to air, visible
      light, and certain relative humidity levels. Both strains could be maximally
      protected from these lethal effects with 100 mM trehalose, a concentration
      calculated to just saturate the interphospholipid spaces in the cell membrane,
      thus preserving the liquid-crystalline structure. The trehalose protection was
      observed for at least 96 h. Trehalose increased viability as much as 2000-4000%
      over nontreated populations. In all cases, exposure to environmental conditions
      was more damaging to the genetically engineered strain.

PMID- 8252919
TI  - Antigen binding of a mouse monoclonal IgG1 is inactivated by heating but not by
      freeze/thaw cycling.
AB  - A mouse monoclonal antibody in ascitic fluid or in purified form was subjected to
      heating or repeated freeze/thaw cycles. Heating the antibody at 80 degrees C for
      10 min completely destroyed its ability to bind to antigen. Unpurified antibody
      in ascitic fluid or purified antibody in buffer was frozen to -196 degrees C in
      liquid nitrogen and then thawed at room temperature. Purified antibody was also
      slowly frozen at -4 degrees C followed by thawing at room temperature. Regardless
      of the manner of freeze/thaw treatment or whether the antibody was purified or
      not, immunologic competence for its antigen was not lost. The results call into
      question the belief that freezing and thawing in all cases are necessarily
      deleterious to antibody structure and function.

PMID- 8252920
TI  - Stability of suicide rates in Europe.

PMID- 8252921
TI  - Introducing Befrienders International.

PMID- 8252922
TI  - Survivors of late life suicide: the family of man.

PMID- 8252923
TI  - Jail suicide--prevention through written protocol (Part 2).

PMID- 8252924
TI  - Hotlines--a case study.

PMID- 8252925
TI  - An aeronautic suicide attempt (1). The lifesaver's story.
AB  - A man without previous flying experience stole an aircraft to commit suicide.
      Here is the narrative from the air traffic controller who guided the man through
      the landing.

PMID- 8252926
TI  - An aeronautic suicide attempt (3). Suicide and self-destructive behavior in
      aviation.
AB  - Approximately 2-3% of all fatal air accidents may be attributed to suicide, and
      in many other accidents in aviation there are grounds for inferring that self
      destructive or suicidal behavior was involved. Narcissistic personality traits
      are of paramount importance for the choice of this suicide method. Precursors
      include undetected depressions, alcoholism, and family problems of pilots.

PMID- 8252927
TI  - Problems with borderline patients in a crisis intervention unit: a case history.
AB  - This article describes some characteristics, advantages, and disadvantages of
      crisis intervention in patients with borderline personality disorder. The
      theoretical issues are illustrated by a case study of a patient with the
      disorder. Therapeutic proceedings are analyzed, with special focus on the
      treatment plan, goal-setting, and termination of therapy. The positive effects of
      the treatment and the patient's unexpected loss of compliance are discussed. Some
      suggestions are made about dealing with such patients in the light of mistakes
      made by the crisis therapist, which produced feelings of inadequacy and
      incompetence in her, stemming from unresolved transference-countertransference
      problems.

PMID- 8252928
TI  - Suicide and parasuicide in ancient personal testimonies.
AB  - Attitudes toward suicide have not always been the same as they are today, and
      understanding the ideas of other cultures and times could enable us to reexamine
      contemporary conceptions of self-killing. Greek and Roman personal testimonies
      were examined to investigate the thesis that ancients did not see suicide as
      caused by psychic or emotional forces. Indeed, though the documents of antiquity
      give us a closer look into personal motives, they demonstrate that even would-be
      self-killers themselves wished to regard suicide as a rational act of volition.

PMID- 8252929
TI  - Deliberate self-harm: an assessment of patients' attitudes to the care they
      receive.
AB  - It has often been suggested that hospital staff have an unfavorable attitude to
      patients who deliberately harm themselves (DSH). Perhaps more important, however,
      is how the staff's attitudes are perceived by the patients, and how effective the
      various groups of professionals are in dealing with DSH patients' problems. In
      this study, questionnaires concerning the attitudes of staff were distributed to
      142 DSH patients just prior to their discharge from hospital. In contrast to
      previous studies, where unfavorable attitudes towards DSH have been reported,
      patients were very positive about the attitudes of the staff. There were
      significant differences between the professional groups encountered, with nurses
      and social workers being particularly favorably regarded. Patients' perception of
      the amount of help they received was found to be highly significantly associated
      with certain staff attributes, in particular sympathy (r = 0.60) and listening
      behavior (r = 0.63). Patients requested a wide range of follow-up to be
      available, particularly emergency contacts (39%) and follow-up by social workers
      (39%) and nurses (37%). Females requested more follow-up than males. The
      implications of the findings for the management of DSH are discussed.

PMID- 8252930
TI  - Train suicides in Brisbane, Australia, 1980-1986.
AB  - Train suicides have not been widely studied, but this mode of suicide is one
      which results in high mortality and disfigurement, considerable trauma to
      bereaved relatives, and often considerable psychological difficulties for those
      indirectly involved such as train drivers and onlookers. The placement of
      psychiatric hospitals close to railways and the advisability of erecting barriers
      have sometimes been hotly debated. This survey of 23 train suicides in Brisbane,
      Australia, addresses these issues. It shows that 57% of the victims had been
      treated for schizophrenia, and 57% were also psychiatric inpatients at the time
      of the incident. Forty eight percent of the deaths occurred close to the regional
      psychiatric hospital. Fifty two percent were young adults aged 15-29 years. All
      suicides occurred during daylight or within 2 h of sunset. These results are
      similar to those from another study in the same city which implicated
      schizophrenia in jumping from heights--also a grossly self-mutilating behavior.
      The erection of barriers to reduce mortality from train suicide was not
      considered a feasible solution for Brisbane, but other cities might benefit from
      such measures.

PMID- 8252931
TI  - Pediatric antimicrobial therapy.

PMID- 8252932
TI  - Nutritional dwarfing.

PMID- 8252933
TI  - Living wills are overrated.

PMID- 8252934
TI  - Withholding and withdrawing nutrition and hydration: surrogates can make this
      decision for incompetent patients.

PMID- 8252935
TI  - Correct aerosol medication use and the health professions. Who will teach the
      teachers?

PMID- 8252936
TI  - Corticosteroids and respiratory muscles. Does it matter?

PMID- 8252937
TI  - Amrinone in cardiac surgical patients with left-ventricular dysfunction. A
      prospective, randomized placebo-controlled trial.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of amrinone for facilitating weaning
      from cardiopulmonary bypass (CPB). DESIGN: Prospective, randomized, double-blind,
      placebo-controlled trial with epinephrine as "rescue" therapy. SETTING: Operating
      room of a large, metropolitan tertiary-care center. PATIENTS: Thirty-nine
      patients with preoperative left ventricular dysfunction undergoing cardiac
      surgery. Thirty-three patients underwent aortocoronary bypass grafting; six
      patients underwent valve replacement for severe mitral or aortic regurgitation.
      INTERVENTIONS: Patients received either amrinone (1.5 mg/kg loading dose plus 10
      micrograms/kg/min maintenance infusion; n = 20) or placebo (n = 19) in a
      randomized double-blind fashion shortly (median, 10.5 min; range, 2 to 24 min)
      before separation from CPB. Inotropic drugs (other than the study drug) were
      withheld prior to separation from CPB unless safety considerations demanded that
      the protocol be broken. Patients who could not be weaned from CPB, as well as
      those with a cardiac index of 2.2 L/min/m2 or less after weaning from CPB,
      received epinephrine (60 to 120 ng/kg/min) by infusion. MEASUREMENTS AND RESULTS:
      Fourteen of 19 patients receiving placebo but only 1 of the 20 patients receiving
      amrinone (p = 0.00001) required epinephrine infusion to separate from bypass. The
      cardiac index of 4 patients receiving placebo (but no patients with amrinone)
      failed to exceed 2.2 L/min/m2 despite epinephrine infusion, requiring the
      protocol to be broken (p < 0.08). Blood concentrations of amrinone determined
      (only in the amrinone group) after separation from CPB confirmed that the dosage
      of amrinone produced an effective blood concentration. Fourteen of 19 patients
      receiving placebo and 17 of 20 patients receiving amrinone required an infusion
      of phenylephrine titrated to maintain systolic blood pressure less than 90 mm Hg.
      Seven patients (four with amrinone and three with placebo) required
      antiarrhythmic drug therapy. The outcome at 3 months was similar in the 2 groups.
      CONCLUSIONS: Amrinone by itself is an effective agent to facilitate weaning from
      CPB, and therapy with amrinone reduced the need for individualized titration of
      epinephrine. Amrinone is as effective as individualized titration of epinephrine
      (after CPB) to improve cardiac function. Patients in the group receiving amrinone
      had no greater need for vasoconstricting agents than did patients in the group
      receiving placebo; however, proactive administration of amrinone before
      separation from CPB appears to offer no greater benefit to high-risk patients
      than selective administration of drugs (epinephrine) only to those patients who
      demonstrate the need for drug support at the time of weaning.

PMID- 8252938
TI  - Anergic response to delayed hypersensitivity skin testing. A predictor of early
      mortality in heart transplant recipients.
AB  - STUDY OBJECTIVE: We set out to determine if there is a significant difference in
      the morbidity and mortality between the anergic and reactive groups. DESIGN: A
      retrospective study of the heart transplant population was performed. SETTING: We
      studied the results of delayed hypersensitivity skin tests (DHSTs) in all cardiac
      transplant recipients at the Cleveland Clinic between May 1985 and November 1991
      to determine whether DHST results were of prognostic significance. RESULTS:
      Preoperative skin testing was reactive to two or more antigens in 90 of the 127
      patients whose DHSTs were interpretable, and the remainder were anergic. Anergic
      response was associated with increased bilirubin and decreased albumin levels,
      but gender, race, primary underlying heart disease, age at transplantation,
      creatinine level, hematocrit, glucose level, and ejection fraction were not
      related to anergy. Anergic patients had significantly higher mortality at 30, 60,
      and 90 days after transplantation, but long-term mortality was not significantly
      different from patients reactive on DHSTs (p = 0.267). CONCLUSION: We conclude
      that the DHSTs provide useful information regarding risk of early mortality after
      heart transplantation.

PMID- 8252939
TI  - The prevalence and significance of a patent foramen ovale in pulmonary
      hypertension.
AB  - In order to determine the prevalence and significance of a patent foramen ovale
      (PFO) in pulmonary hypertension, 58 patients were studied with transesophageal
      echocardiography, right-sided heart catheterization, and exercise testing. In
      order to examine if a PFO might be associated with a better outcome, survival was
      estimated, based on a formula derived from the National Institutes of Health
      Primary Pulmonary Hypertension Registry, for the patients with primary pulmonary
      hypertension (PPH). A PFO was found in 26 percent (15 of 58) of all patients
      studied, 25 percent (10 of 40) of those with PPH, and 28 percent (5 of 18) of
      those with secondary pulmonary hypertension. We found no significant difference
      in any hemodynamic variable or exercise tolerance between the patients with and
      without a PFO, or for subsets of patients with primary and secondary pulmonary
      hypertension. We also found no significant difference in the 1-, 2-, 3-, 4-, or 5
      year estimated survival, for the patients with PPH between those with and without
      a PFO. The prevalence of a PFO in pulmonary hypertension appears similar to the
      normal population. A PFO provides no detectable influence on resting hemodynamics
      or exercise tolerance in patients with pulmonary hypertension and is not clearly
      associated with patients expected to survive longer.

PMID- 8252940
TI  - Myocardial thickening in children with acute myocarditis.
AB  - Two-dimensional echocardiography showed myocardial thickening in 3 of 16 acute
      myocarditis patients in childhood. In all 3 cases, this myocardial thickening was
      transient and diminished within 3 weeks. This myocardial thickening was most
      marked at a few days after the onset; the interventricular septal thickness for
      each case was 13, 24, and 12 mm and the left ventricular posterior wall thickness
      was 13, 24, and 10 mm for each case. Two-dimensional echocardiography also
      revealed contraction disturbances in these three cases at their onset, which
      improved with the diminution of myocardial thickening. The contraction
      disturbance in acute myocarditis, occasionally causing cardiac pump failure,
      seems closely related to this myocardial thickening.

PMID- 8252941
TI  - D-dimer in patients with clinically suspected pulmonary embolism.
AB  - STUDY OBJECTIVE: To determine whether measurement of D-dimer, using an enzyme
      linked immunosorbent assay (ELISA) with a cutoff of 300 ng/ml, and a latex
      agglutination assay with a cutoff of 500 ng/ml, is clinically useful in patients
      with suspected pulmonary embolism (PE). DESIGN: Prospective cohort. SETTING:
      Tertiary care referral center, university-affiliated hospital. PATIENTS: Two
      hundred twenty-one consecutive patients with clinically suspected PE.
      INTERVENTION: All patients had blood drawn to measure levels of D-dimer and
      underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance
      plethysmography (IPG); pulmonary angiography was performed in nine patients.
      Patients were classified as follows: (1) PE-positive; positive pulmonary
      angiography or high probability V/Q scan or non-high-probability V/Q scan and
      either abnormal IPG (either at presentation or on serial testing and confirmed by
      contrast venography) or symptomatic thromboembolic event within 3 months of
      presentation; or (2) PE-negative; normal V/Q scan or normal pulmonary angiography
      or non-high-probability V/Q scan and either normal serial IPG or abnormal IPG
      with normal venography and absence of symptomatic venous thromboembolism within 3
      months of followup. Forty-three patients were classified as PE positive and 178
      patients were classified as PE negative. MEASUREMENTS AND RESULTS: The
      sensitivities, specificities, positive predictive values, and negative predictive
      values of the ELISA and latex agglutination assay were calculated for all
      patients and for the subgroup of patients with non-high-probability V/Q scans.
      The ELISA D-dimer, using a cutoff of 300 ng/ml, showed a sensitivity and negative
      predictive value of 100 percent in all patients and patients with non-high
      probability V/Q scans, but the corresponding specificities were only 26 percent
      and 13 percent, respectively. The latex agglutination assay for D-dimer using a
      cutoff of 500 ng/ml showed the following: sensitivities of 84 percent in all
      patients and 90 percent in patients with non-high-probability scans, negative
      predictive values of 93 percent in all patients, and 98 percent in patients with
      non-high-probability scans and specificities of 56 percent in all patients and 55
      percent in patients with non-high-probability scans. CONCLUSIONS: This study
      demonstrates that an ELISA D-dimer result of less than 300 ng/ml excludes PE but
      occurs in a small proportion of patients with clinically suspected PE. The latex
      agglutination assay, using a cutoff of 500 ng/ml, has potential clinical utility
      in excluding PE in the subgroup of patients with clinically suspected PE and non
      high-probability V/Q scans. However, the 95 percent confidence interval on the
      observed sensitivity of the latex agglutination assay in patients with non-high
      probability V/Q scans is wide. Therefore, these promising results should be
      confirmed in a large clinical trial before the latex agglutination assay is used
      to make management decisions.

PMID- 8252942
TI  - Neural network in the clinical diagnosis of acute pulmonary embolism.
AB  - The purpose of this investigation was to test the hypothesis that computer-based
      pattern recognition can accurately assess the likelihood of acute pulmonary
      embolism (PE) based on readily obtainable clinical characteristics. Data were
      obtained from 1,213 patients who participated in the collaborative study of the
      Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED).
      Characteristics of the history, physical examination, electrocardiograph, chest
      radiograph, and arterial blood gases of patients with suspected acute PE were
      presented to a back propagation neural network. The 1,213 patients were divided
      into training set A (n = 606) and test set B (n = 607). These groups were then
      reversed into training set B (n = 607) and test set A (n = 606). A receiver
      operating characteristic (ROC) curve was constructed from PIOPED clinical
      assessment, and from neural network clinical assessment in groups A and B. Areas
      under the respective ROC curves were 0.7450, 0.7477, and 0.7324. All differences
      were not significant. Areas under ROC curves for PIOPED clinical assessment
      combined with ventilation/perfusion (V/Q) scan results were compared with neural
      network clinical assessment combined with V/Q scan results in groups A and B. The
      respective ROC areas were 0.8324, 0.8203, 0.8496 (all differences not
      significant). These data show that neural networks were able to predict the
      clinical likelihood of PE with an accuracy comparable to experienced clinicians.

PMID- 8252943
TI  - Platelet activation and fibrinopeptide formation in pulmonary hypertension.
AB  - Intravascular thrombosis is postulated to cause or to contribute to the
      development of uncharacterized ("primary") pulmonary hypertension (PPH). To
      assess whether there is ongoing platelet-fibrin thrombosis in patients with PPH,
      we measured specific markers of platelet activation: platelet factor 4 (PF4) and
      beta-thromboglobulin (BTG); of fibrin formation: fibrinopeptide A (FPA); and of
      fibrin dissolution: fibrinopeptide BB1-42 (FPBB1-42) in peripheral venous blood
      from 10 patients with PPH (group 2). Results were compared with those of normal
      volunteers (group 1, n = 9) and with results from patients with pulmonary
      hypertension secondary to congenital heart disease (group 3, n = 7). Both groups
      2 and 3 exhibited severe pulmonary hypertension (mean pulmonary arterial pressure
      = 62 +/- 20 mm Hg and 70 +/- 13 mm Hg, respectively). Mean level of PF4, BTG,
      FPA, and FPBB1-42 in patients with pulmonary hypertension, either primary or
      secondary to congenital heart disease, did not differ from levels in normal
      subjects. Within group 2, levels of platelet proteins and fibrinopeptides did not
      differ between patients who were classified clinically as having plexogenic
      arteriopathy vs thromboembolic disease. These observations suggest that a
      sustained state of abnormal platelet activation and fibrin formation or
      dissolution is not present in patients with established pulmonary hypertension.

PMID- 8252944
TI  - Nasal continuous positive airway pressure in patients with COPD in acute
      respiratory failure. A study of the immediate effects.
AB  - The aim of this study was to assess the effect of nasal continuous positive
      airway pressure (CPAP) breathing on patients with COPD when they are in
      respiratory failure during acute episodes of the disease. We studied 15 male
      patients with COPD who were in acute, unstable condition, without mechanical
      ventilatory support, before and during 4 h of nasal CPAP. The respiratory rate
      decreased (initial, 30 +/- 6; final, 25 +/- 6; p < 0.001), as did the subjective
      sensation of dyspnea (initial Borg index, 3 +/- 3; final, 2 +/- 2; p < 0.05). A
      significant decrease in the average PaCO2 (before, 73 +/- 10 mm Hg; after, 61 +/-
      9 mm Hg; p < 0.001) and a significant increase in the PaO2 (before, 57 +/- 13 mm
      Hg; after 64 +/- 14 mm Hg; p < 0.05) were also observed. Nasal CPAP was generally
      well tolerated. According to these results, nasal CPAP should be considered as a
      possibility for treatment in patients with COPD who are in acute respiratory
      failure, in order to avoid mechanical ventilation.

PMID- 8252945
TI  - External high-frequency ventilation in severe chronic obstructive pulmonary
      disease.
AB  - We studied the effect of external high-frequency oscillation using an oscillator
      (Hayek oscillator [HO]) on 20 patients with severe chronic obstructive pulmonary
      disease (COPD). Of the 20 patients, 10 were eucapnic and 10 were hypercapnic. The
      HO generated frequencies from 60 to 140 cycles/min at an amplitude of 36 cm H2O (
      26 to +10) and at an inspiratory/expiratory (I/E) ratio of 1:1. The results show
      that the HO is a powerful ventilator, reducing end-tidal PCO2 (PETCO2) by 6.7 to
      9.1 mm Hg in eucapnic patients and by 6.1 to 7.9 mm Hg in hypercapnic patients.
      The oxygen saturation increased by 2 to 2.87 percent in the eucapnic patients and
      by 2.6 to 3.7 percent in the hypercapnic group in the various frequencies. The
      rate of elimination of CO2 and the levels of PETCO2 achieved within a short time
      were superior to those reported with other external ventilators. We conclude that
      the HO can be effectively used in severe COPD and respiratory failure for (1)
      assisting ventilation, thus replacing intubation and conventional mechanical
      ventilation, and (2) relieving muscle fatigue in short sessions.

PMID- 8252946
TI  - A comparison of long-term ventilatory support alternatives from the perspective
      of the patient and care giver.
AB  - Tracheostomy, noninvasive intermittent positive pressure ventilation (IPPV)
      methods, and body ventilators can be used for ventilatory support. These methods
      vary with respect to safety, convenience, effect on speech, sleep, swallowing,
      appearance, comfort, and general patient acceptability. The purpose of this study
      was to determine patient and care giver ventilatory support preferences
      concerning these quality of life issues. One hundred sixty-eight predominantly
      neuromuscular patients with greater than 1 month of experience in the use of both
      tracheostomy and noninvasive methods were surveyed. At the time of the study they
      had a mean age of 54.7 +/- 11.4 years, were using ventilatory aids a mean of 17.1
      +/- 6.5 h/d, and had been doing so for 22.7 +/- 13.1 consecutive years. The 59
      respondents who switched from tracheostomy to noninvasive aids significantly
      preferred the latter for every item and unanimously preferred them over all. The
      76 respondents switched from body ventilator use to tracheostomy IPPV
      significantly preferred use of the former for appearance and speech and the
      latter for sleep and security and had no other significant preferences. However,
      the 35 respondents switched from a regimen of noninvasive aids including
      noninvasive IPPV to tracheostomy IPPV significantly preferred the noninvasive
      aids for each item except for sleep, swallowing, and security for which there
      were no significant preferences. We conclude that whether patients switched to or
      from noninvasive ventilatory support regimens which include noninvasive IPPV,
      noninvasive methods are considered by patients to be more convenient, to have
      less untoward effects on speech, appearance and comfort, and are preferred
      overall to tracheostomy IPPV.

PMID- 8252947
TI  - Attended home titration of nasal continuous positive airway pressure therapy for
      obstructive sleep apnea.
AB  - Nasal continuous positive airway pressure (CPAP) therapy for obstructive sleep
      apnea (OSA) is usually titrated in a sleep laboratory with full polysomnographic
      monitoring until apneas, nonapneic desaturation, snoring, and microarousals are
      eliminated. This titration is sometimes done in the second half of the diagnostic
      sleep study or commonly on a separate second full night in the sleep laboratory.
      We performed NCPAP titration in the home in 17 patients with OSA previously
      documented by full polysomnography. Nasal CPAP was titrated at night in the
      patient's home by a registered nurse or polysomnography technician monitoring
      real-time recordings of heart rate, thoracic impedance, oxygen saturation, and
      pressure at the nasal mask on a four-channel recorder (EdenTec, Eden Prairie,
      Minn). Recordings of the nasal CPAP titration night were reviewed later by a
      physician. Apneas, hypopneas, and snoring were successfully eliminated in all
      patients. Mean nasal CPAP pressure was 10.3 +/- 3.2 cm H2O. At the time of a
      follow-up interview, 13 of 17 patients continued to be compliant with nasal CPAP
      therapy. The mean duration of therapy was 13.4 +/- 11.7 months with 7.23 mean
      hours of use for 6.76 nights per week. This compliance compares favorably with
      long-term home nasal CPAP compliance previously reported in patients titrated in
      our sleep laboratory. Home nasal CPAP titration resulted in about a $600 savings
      per patient.

PMID- 8252948
TI  - Reduction of blood loss from diagnostic sampling in critically ill patients using
      a blood-conserving arterial line system.
AB  - STUDY OBJECTIVE: To demonstrate the utility of a new blood-conserving arterial
      line system in reducing blood loss associated with blood drawing in the critical
      care setting. DESIGN: Prospective, randomized, crossover comparison between two
      arterial line systems. SETTING: Medical intensive care unit (ICU); tertiary care
      teaching institution. PATIENTS: Thirty-one patients who required invasive
      arterial blood pressure monitoring throughout their ICU course. INTERVENTIONS:
      For ICU days 1 to 2, patients were randomized to receive either a conventional
      arterial line system or a new blood-conserving arterial line system. On ICU days
      3 to 7, patients with a conventional arterial line were crossed over to the blood
      conserving arterial line, and vice versa. Laboratory blood volumes, mixed discard
      volumes, and blood discard volumes were then recorded to document how much blood
      loss is associated with each aspect of the blood sampling process. RESULTS: The
      mean total volume of blood sent to the laboratory for testing was 257.4 ml. As a
      result of "clearing the line" over the 7-day period, patients with the
      conventional arterial line system lost a mean volume of 340.2 ml of blood mixed
      with heparinized saline solution more than patients with the blood-conserving
      arterial line. In terms of the blood component of the blood-heparinized saline
      solution mixture, use of the conventional arterial line was associated with an
      average of 156.8 ml more blood discarded than with the blood-conserving arterial
      line. CONCLUSION: The new blood-conserving arterial line system provides a simple
      and effective method for reducing blood loss related to diagnostic sampling in
      the critical care setting.

PMID- 8252949
TI  - Nonphysician placement of arterial catheters. Experience with 500 insertions.
AB  - To improve availability of arterial line placement, we developed a nonphysician
      protocol for respiratory therapists to insert arterial catheters. In our
      experience with more than 500 catheter insertions, in which placement lasted from
      1 to 20 days, superficial infection occurred in 5 percent of patients and a major
      complication occurred in only 1 patient. These results show that specially
      trained nonphysician personnel can insert arterial catheters safely when
      following a protocol. Similar reallocation of existing resources should increase
      patient care while decreasing patient care cost in most settings.

PMID- 8252950
TI  - Female asthmatics have increased hypercapnic chemosensitivity during the luteal
      phase which is not associated with decline in airway function.
AB  - To examine whether changes in respiratory chemosensitivity during the menstrual
      cycle are related to worsening of airway functions, hypoxic and hypercapnic
      ventilatory and P0.1 responses, airway function, and serum progesterone levels
      were studied in 11 female asthmatic patients in both the follicular and luteal
      phases. Plasma progesterone levels were 30-fold higher in the luteal phase than
      in the follicular phase (p < 0.0001). The PaCO2 decreased from 37.1 +/- 0.98 (SE)
      mm Hg to 35.1 +/- 0.89 mm Hg (p = 0.05) and HCO3- decreased from 22.4 +/- 0.44
      mEq/L to 20.8 +/- 0.61 mEq/L (p < 0.001), from the follicular phase to the luteal
      phase, respectively. From the follicular to the luteal phase, delta VE/delta
      PACO2 tended to increase from 1.57 +/- 0.12 L/min/mm Hg to 1.91 +/- 0.26 L/min/mm
      Hg (p = 0.08) and delta P0.1/delta PACO2 increased from 0.25 +/- 0.05 cm H2O/mm
      Hg to 0.37 +/- 0.08 cm H2O/mm Hg (p = 0.05). During hyperoxic hypercapnia in the
      luteal phase, VE, f, and mean inspiratory flow increased and TI and TE decreased
      (p < 0.05). There were no differences in the hypoxic ventilatory and P0.1
      responses and airway functional parameters (FEV1, PEF, V50, V25, and Raw) of the
      two phases. The increases in hypercapnic ventilatory and P0.1 responses were
      correlated to the improvement in FEV1 and PEF (p = 0.05 and p < 0.01,
      respectively). These results suggest that, although there is an augmentation of
      hypercapnic chemosensitivity during the luteal phase in female asthmatic
      patients, this is not associated with the decline in airway functions.

PMID- 8252951
TI  - Inhaled furosemide prevents ultrasonically nebulized water bronchoconstriction in
      children with both atopic and nonatopic asthma.
AB  - To determine whether inhaled furosemide can modify the bronchoconstriction
      induced by ultrasonically nebulized distilled water (UNDW) in children with both
      atopic and nonatopic asthma, a single-blind, randomized, placebo-controlled study
      was undertaken. The UNDW inhalation challenge was performed in 21 asthmatic
      children (atopic, 14; nonatopic, 7; mean +/- SEM age, 11.5 +/- 0.5 years), who
      had a fall in FEV1 of at least 20 percent after distilled water inhalation. On
      separate days, these subjects underwent UNDW challenge test after inhalation of
      furosemide (10 mg/body square meters) or placebo (saline solution). Inhaled
      furosemide exerted a protective effect against bronchoconstriction induced by
      UNDW in children with both atopic and nonatopic asthma (p < 0.01, p < 0.05,
      respectively). These results indicate that the protective action of furosemide
      against UNDW-induced bronchoconstriction may be independent of its direct
      inhibitory effect on airway mast cell activation.

PMID- 8252952
TI  - Variations in the use of medication for the treatment of childhood asthma in the
      Michigan Medicaid population, 1980 to 1986.
AB  - Asthma is a leading cause of morbidity in the United States and is a leading
      cause of disability in children. Prevalence has been shown to be highest in male
      children, blacks, and urban residents. Racial and residential differences have
      been attributed to economics. Medicaid claims data allow for the comparison of
      asthma morbidity and treatment of patients with different demography but of low
      socioeconomic status. Michigan Medicaid claims data for recipient children
      between 5 and 14 years of age were used to ascertain demographic factors
      associated with asthma treatment from 1980 through 1986. A cross-sectional
      analysis was used. Black asthmatics were found to receive medical care more
      frequently, but to obtain asthma drugs less frequently than other groups. The
      prevalence of different prescription asthma preparations also varied by race and
      residence. Black, urban residents obtained fixed-combination drugs more
      frequently and steroids less frequently than other groups. Rural patients, in
      general, had fewer medical contacts but obtained more prescription products per
      provider contact, whether black or white. Possible reasons for this variation are
      discussed.

PMID- 8252953
TI  - Gastric asthma? No change in respiratory impedance during intraesophageal
      acidification in adult asthmatics.
AB  - BACKGROUND: In patients with asthma, gastroesophageal reflux (GER) has been shown
      to be a common finding, and a number of investigators have suggested that reflux
      may have a deleterious effect in asthma, either as a result of recurrent
      (micro)aspiration or by some form of a reflex mechanism. AIM OF THE STUDY: To
      measure changes in lung function in response to intraesophageal acid perfusion in
      asthmatics with GER. METHODS: In 12 patients with bronchial asthma and complaints
      suggesting GER with increased reflux scores during 24-h intraesophageal pH
      monitoring, impedance measurements of the respiratory system using the technique
      of forced oscillations and spirometry were performed after intraesophageal
      acidification. RESULTS: No statistically significant changes in FEV1 or in
      respiratory impedance were demonstrated after intraesophageal acid provocation.
      CONCLUSION: No direct effect of intraesophageal acidification on bronchomotor
      tone was demonstrated in asthmatics with GER.

PMID- 8252954
TI  - Pharmacist knowledge and ability to use inhaled medication delivery systems.
AB  - Previous studies have shown that a significant proportion of patients and
      physicians have difficulty using metered dose inhaler (MDI) delivery systems. It
      has been suggested that paramedical personnel such as pharmacists could address
      this problem by serving as patient educators. Few studies have assessed a
      pharmacist's knowledge of and ability to use inhaled devices, including not only
      the conventional MDI but newer devices such as an add-on spacing chamber
      (Aerochamber) and a multidose dry powder inhaler (Turbuhaler). We therefore
      approached all pharmacists in a predefined geographic area of a large city in
      order to evaluate their knowledge of and ability to use inhaled medications. Of
      62 pharmacists approached, 45 (73 percent) agreed to participate. Ability to use
      the conventional MDI, Aerochamber (A), and Turbuhaler (T) was graded by a trained
      observer using a checklist of 11 essential steps. The percentage of pharmacists
      performing greater than 6, 8, and 10 steps correctly for each device was MDI = 96
      percent, 87 percent, 62 percent; MDI + A = 80 percent, 76 percent, 47 percent; T
      = 67 percent, 64 percent, 29 percent. The most common problems with the MDI were
      forgetting to shake prior to use and coordinating inspiration with actuation. The
      most common problems with the MDI + A were forgetting to shake prior to use,
      remembering to inspire after actuation, and breath holding after inspiration. The
      most common difficulty with the T was total unfamiliarity with the device with 33
      percent of pharmacists achieving less than 2 steps correctly. The observer
      subsequently administered a questionnaire of 11 clinically relevant questions for
      each of the devices tested. The mean score was 50 percent with only 21 percent of
      pharmacists scoring above 70 percent. Thirty-three percent of respondents had no
      instruction in device use beyond reading the packing insert; 40 percent had
      received instruction from a pharmaceutical representative; only 24 percent had
      received instructions from professional school. We conclude that a pharmacist's
      knowledge of inhaling devices is roughly proportional to the length of time the
      device has been available and that pharmacists form another group of health care
      professionals who require further teaching regarding inhaled medication delivery
      systems.

PMID- 8252955
TI  - A comparison of the bronchodilating effects of oxitropium bromide and fenoterol
      in patients with chronic obstructive pulmonary disease.
AB  - Oxitropium bromide is a novel anticholinergic bronchodilator agent. The purpose
      of this study was to compare the bronchodilating and cardiovascular effects of
      oxitropium (0.2 mg), fenoterol (0.4 mg), combined oxitropium and fenoterol (0.2
      mg and 0.4 mg, respectively) over a 10-h test period. Fourteen patients with
      chronic obstructive pulmonary disease (COPD) (FEV1, 0.95 +/- 0.38L) were studied
      in a randomized, double-blind, placebo-controlled trial. Combined oxitropium and
      fenoterol produced significantly greater improvements in FEV1 over a time span of
      15 min to 10 h and in the area under the time-FEV1 curve (AUC) than either
      oxitropium or fenoterol alone. The effects of oxitropium on both FEV1 and AUC
      values were similar to those of fenoterol. Oxitropium resulted in a greater
      increase in FEV1 than the placebo even after 10 h. In contrast; fenoterol
      produced a significant improvement in the FEV1 for only 15 min to 4 h. Oxitropium
      showed no adverse cardiovascular effects, whereas fenoterol was associated with
      an increased heart rate at 15 min and 1 h after the administration. We conclude
      that oxitropium bromide is an effective and safe bronchodilator for even elderly
      patients with COPD.

PMID- 8252956
TI  - Prediction of maximal exercise capacity in obstructive and restrictive pulmonary
      disease.
AB  - We evaluated the predictive value of resting pulmonary function tests (PFTs) in
      the determination of maximal exercise capacity in patients with obstructive and
      restrictive ventilatory disease. We performed resting PFTs and an incremental
      exercise study on a bicycle ergometer in 146 patients with chronic obstructive
      pulmonary disease (COPD) and 68 patients with restrictive disease. The patients
      with obstructive disease were further subdivided into mild, moderate, and severe
      based on the severity of their airway obstruction (mean +/- SD:FEV1, 2.78 +/-
      0.77, 2.12 +/- 0.74, and 1.06 +/- 0.47, respectively). Correlation coefficients
      for PFTs vs VO2max and VEmax in restricted patients was generally low (DL = 0.67
      and 0.34, IC = 0.58 and 0.35, FVC = 0.57 and 0.35, TLC = 0.35 and 0.18). In
      patients with COPD, the maximum voluntary ventilation (MVV) was the single best
      predictor of VO2 in all groups with correlation coefficients of 0.75, 0.69, and
      0.89 in the mild, moderate, and severe subgroups, respectively. Similarly, the
      MVV was the best predictor of VEmax in all groups with correlation coefficients
      of 0.59, 0.64, and 0.89 in the three subgroups. The correlation with FEV1 was
      slightly less for both VO2max (0.69, 0.65, and 0.87) and VEmax (0.52, 0.64, 0.64)
      in the mild, moderate, and severe subgroups, respectively. Our findings show that
      PFTs are unreliable in predicting VEmax and VO2max in restricted patients. In
      patients with obstruction, the MVV is the single best predictor of VO2max and
      VEmax in all three categories, but was not significantly improved by stepwise
      multiple regression with additional PFT variables. Higher correlations were
      obtained in the severe group in whom the correlation with VO2max and VEmax was
      0.89. However, the 95 percent confidence interval of the estimate for VO2 and VE
      was relatively large (+/- 0.16 L/min and +/- 6.6 L/min, respectively). We
      conclude that although several PFTs correlate significantly with maximum
      exercise, the large variance precludes their use to accurately predict maximum
      performance in individual patients with COPD.

PMID- 8252957
TI  - Modification of exercise performance by sharp reduction of blood pressure. A
      study in patients with uncomplicated hypertension.
AB  - We evaluated exercise performance in 14 patients with uncomplicated essential
      hypertension 1 h after the administration of a single dose of placebo, nifedipine
      (20 mg), captopril (50 mg), and propranolol (80 mg). Drugs were administered at
      the same time of day following a randomized, double-blind protocol. Mean resting
      blood pressure (+/- SE) was 135 +/- 3 mm Hg with placebo administration, 118 +/-
      4 with captopril, 110 +/- 4 with nifedipine, and 115 +/- 5 with propranolol and
      increased with exercise to 163 +/- 4, 146 +/- 3, 136 +/- 4, 136 +/- 4,
      respectively. Oxygen consumption at peak exercise and at ventilatory anaerobic
      threshold (VAT) was 25.2 +/- 1.1 and 18.1 +/- 1.0 ml/min/kg with placebo. Only
      propranolol (-2.3 ml/min/kg) decreased peak exercise oxygen consumption. Oxygen
      consumption at VAT was reduced by nifedipine and propranolol but unaffected by
      captopril. The effects on exercise capacity of blood pressure reduction in
      hypertensive patients are dependent on the drug utilized and are not related to
      the amount of blood pressure reduction. The lowered oxygen consumption at VAT
      observed with nifedipine and propranolol, and not with captopril, might be due to
      an excessive downward shift of the muscle perfusion pressure--oxygen consumption
      relationship which might take place during exercise.

PMID- 8252958
TI  - Hyperoxic training increases work capacity after maximal training at moderate
      altitude.
AB  - High-intensity training may be difficult to sustain due to limitations in
      systemic oxygen transport, particularly at high altitudes. The purpose of this
      study was to examine the effects of a high-intensity training protocol using
      hyperoxic gas breathing in athletes "maximally trained" at an altitude of 1,600
      m. Five subjects underwent progressive cycle training until they reached a
      plateau of aerobic capacity, maximal workload, and endurance time at 85 percent
      maximal workload. Significant decreases (2 to 6 percent) in arterial oxygen
      saturation were found after the 85 percent maximal workload tests. Training
      intensity was then increased to 95 percent maximal workload while the subjects
      breathed a gas mixture containing at least 70 percent oxygen. After 6 weeks of
      hyperoxic training, exercise parameters were compared with the plateau values
      obtained during the baseline training period. Total time during maximal cycle
      testing increased from 19.1 to 19.6 min (p = 0.015), heart rate at 85 percent
      maximal workload decreased from 168 to 163 bpm (p = 0.047), and endurance time at
      85 percent maximal workload increased from 6.2 to 8.2 min (p = 0.012). There was
      a trend toward improvement of maximal workload. We conclude that hyperoxic
      training increases work capacity after attainment of "maximal training" at
      moderate altitude.

PMID- 8252959
TI  - A comparison of rotation and nonrotation in tetracycline pleurodesis.
AB  - Previously, we have shown rapid and complete dispersion of tetracycline
      hydrochloride in the pleural space following chest tube instillation. To assess
      the clinical relevance of this observation, we randomized patients with
      symptomatic pleural effusions to rotation (R) (n = 19) and nonrotation (NR) (n =
      21) groups following administration of tetracycline hydrochloride, 20 mg/kg (n =
      30); 300 mg of minocycline hydrochloride (n = 6); and 500 mg of doxycycline
      hydrochloride (n = 4) through a chest tube. Patients in the R group were
      maneuvered through six positions for the 2 h that the chest tube remained
      clamped. The NR patients remained supine for 2 h. Rotation and nonrotation groups
      were similar in demographics, source of pleural effusion, symptoms, and serum and
      pleural fluid analyses (all p = NS). A chest radiograph was scored based on
      pleural fluid recurrence throughout survival or up to 12 months. Survival,
      duration of chest tube instillation, and success of pleurodesis assessed by
      radiographic pleural fluid reaccumulation (73.7 vs 61.9 percent; R vs NR) were
      similar (p = NS). Rotational maneuvers appear to offer no benefit to the success
      of pleural symphysis after intrapleural instillation of tetracycline class
      agents.

PMID- 8252960
TI  - Resection of pulmonary blebs and pleurodesis for spontaneous pneumothorax.
AB  - Over a 20-year period, 83 patients underwent operative pleurodesis with resection
      of pulmonary blebs for spontaneous pneumothorax. Follow-up for all patients was
      between 5 and 25 years, with a mean of 9.1 years. There were five early (5.6
      percent) and three late recurrences (3.6 percent). There were no deaths or need
      for blood transfusion in our series. There was a low incidence of postoperative
      fever (n = 8), minor wound infection (n = 6), air leak (n = 6), or pneumonia (n =
      2). The low morbidity and recurrence rates compare favorably with published
      series of alternative treatment options for spontaneous pneumothorax.

PMID- 8252961
TI  - Evaluation of conventional chest tube therapy for iatrogenic pneumothorax.
AB  - STUDY OBJECTIVE: To assess conventional, large chest tube therapy in iatrogenic
      pneumothorax and to determine the optimal moment when to use more invasive
      procedures. DESIGN: Retrospective chart review. SETTING: Medical intensive care
      unit of a university hospital. PATIENTS: Forty-seven patients with needle-induced
      iatrogenic pneumothorax. Twenty-four patients had an underlying pleural or
      pulmonary disorder. INTERVENTIONS: After insertion of a 20- to 24-French plastic
      chest tube connected to an underwater seal, suction was maintained until gas
      egress stopped or up to 10 days in patients with a persisting gas leak. RESULTS:
      In 96 percent, a definite occlusion of the pneumothorax was achieved. In all
      patients without an underlying lung disorder, gas egress stopped definitely after
      72 h. In the presence of an underlying lung disorder, 92 percent of the
      pneumothoraces were healed after 10 days of continuous suction therapy. At 72 h,
      only 71 percent of the latter group were healed (p < 0.05 vs patients without
      lung disease). No major complication of chest tube therapy occurred. CONCLUSION:
      Conventional chest tube therapy is a safe and effective treatment for iatrogenic
      pneumothorax. In patients with an underlying lung disease, gas egress may last
      for up to 10 days. In these patients, the earlier use of a more invasive approach
      may be justified if the air leak persists.

PMID- 8252962
TI  - Alveolar macrophage subpopulations in patients with active pulmonary
      tuberculosis.
AB  - Alveolar macrophages are a heterogeneous cell population. The heterogeneity of
      alveolar macrophages recovered by bronchoalveolar lavage (BAL) from 12 patients
      with active pulmonary tuberculosis (TB) and 10 normal subjects was studied using
      Percoll density fractionation. The numbers and subsets (on the basis of CD3, CD4,
      and CD8 monoclonal antibodies) of lymphocytes in BAL were measured by flow
      cytometry. Alveolar macrophages recovered from patients with TB were mainly in
      the lower-density fractions (< 1.030 and 1.030 to 1.040 g/ml), whereas alveolar
      macrophages from normal subjects were in the higher-density fractions (1.050 to
      1.070 and > 1.070 g/ml). There were no significant differences in alveolar
      macrophages' repartition between smokers and nonsmokers in either patients with
      TB or normal subjects. The significant changes in the proportions of the lowest
      fraction and the higher fractions of alveolar macrophages in patients with TB
      were not altered after division of our patients into smoker and nonsmoker
      subgroups when compared with corresponding subgroups in normal subjects. The
      proportion of the alveolar macrophages in the lowest fraction was inversely
      related to the bacterial load of sputum and the disease extent on chest
      radiography in TB patients. The CD4/CD8 ratio was significantly higher in
      patients with TB. This study shows that alveolar macrophages from TB patients are
      heterogeneous with hypodense cells predominant probably by interaction with T
      lymphocytes. Changes in the proportions of alveolar macrophages within
      subpopulations may be of critical importance in determining the overall response
      of the lung to TB infection.

PMID- 8252963
TI  - Mycobacterium gordonae: a treatable disease in HIV-positive patients.
AB  - PURPOSE: To evaluate the pathogenicity of Mycobacterium gordonae in patients with
      and without human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS:
      Twenty-one HIV-positive and 15 HIV-negative patients in a tertiary care center. A
      descriptive, case-control, and cohort study with a review of the literature with
      a computer-based data research. RESULTS: The 15 HIV-negative patients had
      colonization only. Seven HIV-positive patients had colonization, 12 had possible
      disease, and 2 had dissemination. The two patients with definitive dissemination
      improved objectively with treatment. CONCLUSION: Mycobacterium gordonae in HIV
      negative patients is rarely a pathogen. In HIV-positive patients with a low CD4+
      cell count, it can cause significant disease and treatment is beneficial.

PMID- 8252964
TI  - Respiratory failure complicating rubeola.
AB  - We reviewed the charts of 19 patients with the diagnosis of measles who were
      admitted to the pediatric intensive care unit for respiratory failure requiring
      intubation and mechanical ventilation. Patients studied were admitted during the
      period June 1989 to June 1990. The mean age was 19 months (range, 3 to 51
      months). The cause for respiratory failure fell into two groups: 47 percent
      developed pneumonitis and refractory hypoxemia. Patients with pneumonitis and
      hypoxemic respiratory failure had a 56 percent mortality. An oxygenation index of
      greater than 40 for 4 h separated survivors from nonsurvivors (oxygenation index
      = [mean airway pressure x FIo2/PaO2 x 100]). Patients with tracheitis alone all
      survived. In these patients the organism primarily responsible was Staphylococcus
      aureus (70 percent). Two of the seven patients with S aureus tracheitis had signs
      and symptoms of toxic shock syndrome and we subsequently demonstrated toxic shock
      syndrome toxin 1 in both patients.

PMID- 8252965
TI  - The effect of corticosteroids on inspiratory muscle performance in humans.
AB  - Functional alterations in the inspiratory muscles were evaluated in patients
      receiving corticosteroids for diseases other than respiratory. Inspiratory muscle
      strength, as expressed by the maximal inspiratory mouth pressure (PImax), and
      inspiratory muscle endurance (PmPeak/PImax), using a pressure threshold breathing
      device, were evaluated in eight patients with normal pulmonary and inspiratory
      muscle functions (two patients with rapidly progressive glomerulonephritis, two
      with glomerulonephritis with minimal changes, two with idiopathic
      thrombocytopenic purpura, and two with subacute thyroiditis). There was a gradual
      decrease in both inspiratory muscle strength and endurance following
      corticosteroid administration. After 8 weeks of treatment PmPeak/PImax decreased
      from 84.4 +/- 2.4 to 67.9 +/- 3.1 percent (p < 0.001), while inspiratory muscle
      strength dropped from 126.9 +/- 9.6 to 86.5 +/- 7.4 cm H2O (p < 0.005). Gradual
      steroid dosage tapering resulted in marked improvement in both strength and
      endurance; the inspiratory muscle strength rose significantly to 112.2 +/- 8.1 cm
      H2O (p < 0.0005) when steroid treatment was stopped, and even more significantly
      6 months later (to 123.1 +/- 8.1 cm H2O [p < 0.0001]), and the PmPeak/PImax rose
      to 60.6 +/- 3.4 percent (p < 0.001) and to 74.7 +/- 3.2 percent (p < 0.0001),
      respectively. We conclude that corticosteroids have a significant deteriorating
      effect on respiratory muscle function in humans. This weakness is reversible
      while tapering steroid dosage. Steroid therapy should be reconsidered in patients
      with underlying lung disease.

PMID- 8252966
TI  - Hemorrhagic rhinitis. An immunologic disease due to hexahydrophthalic anhydride.
AB  - This is a descriptive study of six men who had been occupationally exposed to
      heated epoxy resin containing hexahydrophthalic anhydride (HHPA) who presented
      with rhinitis, nasal mucosal erosions, and significant epistaxis; three also had
      asthma. When they were removed from exposure to HHPA, the rhinitis symptoms,
      nasal erosions, and epistaxis resolved spontaneous. All six had high titers of
      IgG and IgE against HHP-HSA as determined by an enzyme-linked immunosorbent assay
      (ELISA). Other asymptomatic workers with similar HHPA exposure had ver low or
      negative titers of IgG and IgE against HHP-HSA. We conclude that these results
      are very suggestive of an immunologic mechanism being responsible for the
      rhinitis, nasal mucosal erosions, and epistaxis that occurred in the six
      described HHPA workers.

PMID- 8252967
TI  - Radiologic abnormalities of the sternum in Turner's syndrome.
AB  - Various skeletal abnormalities, including chest deformity, have been reported
      with Turner's syndrome. We report radiologic findings of the sternum on lateral
      chest roentgenograms in 15 children and adolescents with Turner's syndrome, whose
      ages ranged between 2 weeks and 20 years. Eight had associated congenital heart
      disease (CHD). Twelve patients (80 percent) had various sternal abnormalities; 5
      had short sternum, 3 had premature fusion of the manubrio-sternal junction, and 4
      had premature fusion of the mesosternum. Five had decreased ratio of sternal body
      to manubrium. Three patients had two ossification centers of the manubrium. Four
      patients had bowing of the mesosternum; three of these had mild pectus excavatum
      also. In this series, children with and without CHD had similar sternal
      abnormalities. Although not pathognomonic, sternal abnormalities on a lateral
      chest roentgenogram are common skeletal abnormalities associated with Turner's
      syndrome and are independent of associated CHD. In our series of 15 patients, 10
      had monosomy (45,X) on blood karyotype; 7 of them had associated CHD. This is the
      first systematic analysis of radiologic abnormalities of the sternum in Turner's
      syndrome and includes findings not previously reported.

PMID- 8252968
TI  - Humidification in the intensive care unit. Prospective study of a new protocol
      utilizing heated humidification and a hygroscopic condenser humidifier.
AB  - STUDY OBJECTIVE: Determine the utility of a proposed algorithm in allowing safe,
      efficient humidification in mechanically ventilated patients using both a
      hygroscopic condenser humidifier (HCH) and heated humidifier (HH). DESIGN: A
      prospective study using an algorithm to chose humidification devices based on
      physical examination and sputum characteristics. SETTING: All patients admitted
      to the surgical ICU. PATIENTS: One hundred twenty consecutive patients requiring
      mechanical ventilation (MV) were studied. INTERVENTIONS: Patients were examined
      by the attending respiratory care practitioner and given either an HCH or HH. If
      patients demonstrated any of the following--thick or tenacious secretions, core
      temperature < 32 degrees C, or bloody secretions--they were given an HH. All
      others used an HCH. If any of the above conditions occurred during HCH use, the
      patient was given an HH. MEASUREMENTS AND RESULTS: Duration of ventilation,
      incidence of nosocomial pneumonia, ventilator circuit colonization, and mortality
      were determined for patients in each group. Cost of humidification devices,
      number of suctioning procedures per day, and volume of saline solution instilled
      were also recorded. Initially, 27 percent (32/120) of patients used an HH and 73
      percent (88/120) used an HCH. During the study, ten patients required changing to
      an HH during HCH use. Patients in the HH group were more likely to have
      preexisting lung disease and had a longer duration of ventilation (83 +/- 21 h)
      and higher mortality (21 percent). Patients in the HCH group were more likely to
      be postoperative, had shorter durations of ventilation (38 +/- 14 h), and lower
      mortality (9 percent). There was no difference in the incidence of nosocomial
      pneumonia between the two groups (9 percent vs 6 percent) and endotracheal tube
      occlusion did not occur in either group. Circuit colonization was common in the
      HH group (64 percent) but rate in the HCH group (5 percent). Cost per day was
      significantly less for the HCH group ($4 vs $19.80). Patients who required a
      change from HCH to HH did so at a mean of 5 days. CONCLUSION: The proposed
      algorithm resulted in cost-efficient and safe application of humidification
      devices in patients in the surgical ICU.

PMID- 8252969
TI  - Analysis of indications for intensive care unit admission. Clinical efficacy
      assessment project: American College of Physicians.
AB  - OBJECTIVE: To formulate recommendations for the development of intensive care
      unit (ICU) admission policies. DESIGN: Literature review of published reports
      over the period 1966 to 1991 pertaining to admission criteria for intensive care
      or coronary care units (CCUs). PATIENTS: Studies identifying patients least
      likely to benefit from ICU or CCU admission were analyzed. Patient populations of
      interest included adults (> or = 18 years of age) with medical conditions
      possibly requiring intensive care; trauma patients were excluded. MEASUREMENTS
      AND MAIN RESULTS: Of 970 articles identified as being pertinent to intensive
      care, only two case-control studies used the direct method of measuring the
      effect of ICU intervention on mortality. No studies were found that compared
      outcomes of low-risk patients treated in a CCU vs those treated in alternative
      hospital locations, and none identified patients with a very high probability of
      a bad outcome. CONCLUSIONS: The use of decision-making models for ICU and CCU
      admissions must be tested in prospective, randomized clinical trials. Critical
      care units and ICUs should be studied separately. Existing studies of early
      discharge from CCUs need to be summarized and evaluated. The triaging of ICU
      patients to alternative hospital locations needs to be evaluated, as do existing
      predictive models for early triage decision-making.

PMID- 8252970
TI  - Analysis of indications for early discharge from the intensive care unit.
      Clinical efficacy assessment project: American College of Physicians.
AB  - OBJECTIVE: To formulate recommendations for the development of early intensive
      care unit (ICU) discharge criteria for low-risk monitor patients. DESIGN:
      Literature review of published reports over the period 1966 to 1991 pertaining to
      ICU discharge criteria. PATIENTS: Studies identifying patients admitted to ICUs
      who could be characterized as low risk. Patient populations of interest included
      adults (> or = 18 years of age) with low-risk medical or mixed medical/surgical
      conditions; cardiac care unit and burn patients were excluded. MEASUREMENTS AND
      MAIN RESULTS: Of 1,492 articles identified as being pertinent to ICU discharge,
      only 2 studies (by the same group of investigators) were found that distinguished
      low-risk populations among medical and mixed medical/surgical ICU patients. The
      physiologic component of the Acute Physiology and Chronic Health Evaluation
      (APACHE) was used in both of these studies to ascertain the degree of risk. No
      studies were found that compared outcomes of low-risk patients remaining in the
      ICU after 24 h with those transferred to other hospital locations. CONCLUSIONS:
      Objective methods (such as APACHE III) should be used to identify low-risk
      patients at 24 h post-ICU admission. A multicenter study should be conducted to
      compare outcomes on patients identified as low risk who are randomly assigned to
      alternative hospital locations for treatment versus those assigned to continued
      ICU treatment until routine ICU discharge. Mortality and quality of life data
      should be used as outcome measures (prior to ICU admission and 6 months post-ICU
      discharge).

PMID- 8252971
TI  - Prevalence and severity of neurologic dysfunction in critically ill patients.
      Influence on need for continued mechanical ventilation.
AB  - OBJECTIVE: The relative importance of neurologic dysfunction in critically ill
      mechanically ventilated patients has not been well studied. This study
      investigates the prevalence of neurologic dysfunction in critically ill
      mechanically ventilated patients and its influence on preventing the
      discontinuation of mechanical ventilation and patient outcome. DESIGN:
      Prospective study. SETTING: University-based, tertiary care center. PATIENTS: All
      eligible adult patients mechanically ventilated for more than 48 h were included.
      A total of 66 patients were evaluated. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: Two independent questionnaires, one completed by the critical care
      attending physician documenting the major clinical factors necessitating
      continued mechanical ventilation, and a second questionnaire, completed by a
      critical-care trained neurologist documenting neurologic status and objective
      cardiopulmonary status formed the basis for outcome measurements. Respiratory and
      physiologic data, the patient's clinical conditions, and outcome (mortality) were
      also included in the database. RESULTS: Pulmonary factors were the major reason
      for prolonged ventilation in only 51 percent of the patient evaluations.
      Neurologic status was the major factor necessitating continued mechanical
      ventilation in 32 percent of the patient evaluations and a significant
      contributing factor in an additional 41 percent. Of the neurologic factors,
      diminished level of consciousness was the major cause of continued ventilatory
      support. This was usually due to a systemic illness, rather than a primary
      central nervous system disorder. Mortality was significantly lower in patients
      who continued to require mechanical ventilation after 48 h because of neurologic
      factors as opposed to pulmonary factors (15 percent vs 72 percent, p = 0.002).
      CONCLUSIONS: There is a high prevalence of neurologic dysfunction in critically
      ill patients and this problem plays a significant role in preventing the
      discontinuation of mechanical ventilation. Altered mental status is a major
      factor necessitating continued mechanical ventilation in combined medical
      surgical intensive care units.

PMID- 8252973
TI  - Mechanical ventilation. American College of Chest Physicians' Consensus
      Conference.

PMID- 8252972
TI  - Transvascular transport of 67Ga in the lungs after cardiopulmonary bypass
      surgery.
AB  - STUDY OBJECTIVE: To examine the effect of cardiac surgery with cardiopulmonary
      bypass (CPB) on pulmonary vascular permeability. DESIGN: A prospective, serial
      study. SETTING: Department of nuclear medicine and intensive care units of a
      university hospital. PATIENTS: Twelve consecutive patients were studied, before
      and immediately after elective cardiac surgery using CPB (group 1), and 4
      consecutive, artificially ventilated patients with acute cardiogenic pulmonary
      edema (group 2). MEASUREMENTS AND RESULTS: The kinetics in blood and over both
      lungs were measured, using two mobile probes at the bedside, of intravenously
      injected 67Ga, assumed to bind to circulating transferrin, and in vitro 99mTc
      labeled red blood cells to account for pulmonary blood volume. From data recorded
      in time (1 h), a pulmonary leak index (PLI), the time constant of transport of
      67Ga from the intravascular to the extravascular space of the lung, was
      calculated and values for both lungs were averaged. In group 1, the PLI (.10(
      3).min-1, mean +/- SD) was 8.2 +/- 3.7 before and 17.0 +/- 13.5 after CPB surgery
      (p < 0.01) and changes directly related to the duration of CPB. In four patients
      with a CPB duration > or = 120 min, the PLI, 31.1 +/- 16.3.10(-3).min-1, exceeded
      2 SD plus mean preoperative PLI. Changes in PLI tended to relate inversely to
      changes in arterial WBC, which, in turn, inversely related to CPB duration. The
      PaO2/FIO2 ratio decreased and tended to relate inversely to PLI after surgery. No
      patient developed alveolar pulmonary edema on chest radiograph. In group 2, the
      PLI was 11.1 +/- 3.1.10(-3).min-1 (NS from group 1 preoperative PLI).
      CONCLUSIONS: Cardiopulmonary bypass induces a pulmonary vascular leak, as
      assessed by 67Ga kinetics using a bedside detection technique, in some cardiac
      surgery patients with prolonged CPB. This leak may reflect pulmonary vascular
      injury and increased permeability, following activation of leukocytes by CPB and
      subsequent pulmonary sequestration, rather than increased filtration through
      pressure factors. It may contribute to impaired gas exchange, even in the absence
      of manifest alveolar edema of the lungs, after surgery.

PMID- 8252974
TI  - Adenosine: diagnostic and therapeutic uses in cardiovascular medicine.

PMID- 8252975
TI  - Endotoxin in human disease. Part 2: Biologic effects and clinical evaluations of
      anti-endotoxin therapies.

PMID- 8252977
TI  - Interstitial infiltrates in a patient with small cell lung carcinoma.

PMID- 8252976
TI  - Effects of thoracotomy on respiratory system, lung, and chest wall mechanics.
AB  - Nineteen rats were sedated, anesthetized, paralyzed, and mechanically ventilated.
      The respiratory, lung, and chest wall elastances (Est-rs, Est-L, Est-w);
      respiratory system, pulmonary, and chest wall total resistances (Rtot-rs, Rtot-L,
      Rtot-w); respiratory system, pulmonary, and chest wall initial resistances (Rinit
      rs, Rinit-L, Rinit-w); and respiratory system, pulmonary, and chest wall
      difference resistances (Rdiff-rs, Rdiff-L, Rdiff-w) were determined before and
      after thoracotomy using the end-inflation occlusion method. Rinit reflects the
      Newtonian resistances and Rdiff represents the viscoelastic/inhomogeneous
      pressure dissipations in the system. Rtot = Rinit+Rdiff, ie, total resistance.
      The animals were submitted to either anterolateral thoracotomy (group A, n = 7),
      median sternotomy (group B, n = 6), or median sternotomy under PEEP while the
      lungs were exposed (group C, n = 6). In groups A and B, statistically significant
      increases in Rdiff-rs significantly augmented Rtot-rs. The former results were
      entirely secondary to significant increases in Rdiff-L, which naturally raised
      Rtot, L. Resistance was not altered in group C rats. Thus, anterolateral
      thoracotomy and median sternotomy increases Rtot-rs as a consequence of augmented
      Rdiff-L, but this finding could be prevented by the use of PEEP. Est-rs and Est-L
      increased in the three groups after surgery. Groups D and E were comprised of
      four animals each. Both underwent median sternotomy and in group E, PEEP was
      applied. Histopathologic examination of the lungs demonstrated a higher degree of
      lung collapse in group D.

PMID- 8252978
TI  - Reversible hypotension following pulmonary embolism in a 33-year-old woman with
      hypothyroidism and vitiligo.

PMID- 8252979
TI  - Why nutrition and hydration should not be withheld from patients.

PMID- 8252980
TI  - Delayed perforation of the esophagus by a closed thoracostomy tube.
AB  - We report on a previously undocumented complication of a trocar-free thoracostomy
      tube--delayed perforation of a normal esophagus. The complication presented
      clinically with fever and copious enteric drainage four days after thoracostomy
      tube insertion. Diagnosis was established by a contrast study of the esophagus.
      Retrospectively, the postinsertion chest radiograph showed the offending
      thoracostomy tube tip impinging on the posterior mediastinum, displacing an
      indwelling nasogastric tube. Early recognition and repositioning of the
      thoracostomy tube is the key in preventing this rare but serious complication.

PMID- 8252981
TI  - Bronchiolitis obliterans organizing pneumonia. Diagnosis by transbronchial
      biopsy.
AB  - Transbronchial biopsy (TBB) has been considered to be inadequate for the
      diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). We describe
      herein two patients with interstitial pulmonary disease in whom the diagnosis of
      BOOP was achieved by TBB. The two patients presented with progressive dyspnea,
      cough, tachypnea, and fine end-inspiratory crackles. The radiologic findings
      disclosed patchy alveolar infiltrates. Pulmonary function tests showed a
      restrictive pattern and decreased diffusing capacity. The pathologic findings
      disclosed bronchioles, alveolar ducts, and alveoli infiltrated with mononuclear
      cells. The lumina were obliterated with fibroblasts and loose granulation tissue.
      Corticosteroid treatment resulted in significant improvement. Transbronchial
      biopsy should be considered as a useful diagnostic tool for BOOP.

PMID- 8252982
TI  - Persistent bronchopleural fistula in a patient with adult respiratory distress
      syndrome. Treatment with pressure-controlled ventilation.
AB  - Bronchopleural fistula (BPF) continues to present a treatment problem in
      mechanically ventilated patients. We report a patient with a traumatic BPF,
      pneumonia, and adult respiratory distress syndrome (ARDS) who was successfully
      ventilated with pressure-controlled ventilation (PCV). This mode, by allowing the
      use of lower inspiratory airway pressures, may promote closure of the fistula.

PMID- 8252983
TI  - Prolonged survival after heart-lung transplantation in systemic lupus
      erythematosus.
AB  - Patients with multisystem involvement of connective tissue disorders are
      generally excluded from consideration for heart-lung and lung transplantation
      because of profound donor organ shortages. A 23-year-old woman with systemic
      lupus erythematosus (SLE) was referred for evaluation of severe, progressive
      pulmonary hypertension. She underwent an uneventful heart-lung transplant and
      received cyclosporine A, azathioprine, and prednisone on a long-term basis.
      Bronchiolitis obliterans resulted in the development of moderate airflow
      obstruction 18 months after transplantation, but the process was stabilized with
      augmented immunosuppression consisting of high-dose parenterally administered
      corticosteroids, and subsequently a course of antithymocyte globulin. Four years
      after transplant, despite the persistence of reduced complement levels, the
      patient remains functionally well without clinical manifestations of SLE. This
      patient's long-term successful outcome indicates that connective tissue disorders
      such as SLE do not necessarily represent absolute contraindications to heart-lung
      and lung transplantation.

PMID- 8252984
TI  - Circulating immune complexes with pulmonary hemorrhage during pregnancy in
      idiopathic pulmonary hemosiderosis.
AB  - Circulating immune complexes occurred during pulmonary hemorrhage in a pregnant
      patient with idiopathic pulmonary hemosiderosis, an association not previously
      reported. The patient required mechanical ventilation, but recovered; after a
      prolonged hospitalization, she was delivered of a healthy infant without further
      complications.

PMID- 8252985
TI  - Esophageal obstruction in a tracheostomized infant.
AB  - Partial esophageal obstruction was an unusual complication of tracheostomy in an
      infant. Emesis and failure to thrive prompted a modified barium-swallow study,
      which revealed that the tracheostomy tube was causing an obstruction in the
      proximal esophagus. Use of a shorter, customized tube eliminated the esophageal
      obstruction, allowing normal feeding and weight gain.

PMID- 8252986
TI  - Mitral prosthetic dehiscence with laminar regurgitant flow signals assessed by
      transesophageal echocardiography.
AB  - A patient with a Bjork-Shiley mitral prosthesis developed progressive heart
      failure without heart murmur and hemolysis. The prosthetic dehiscence was not
      diagnosed using transthoracic echocardiography, but transesophageal
      echocardiography. The regurgitant signals revealed laminar flow pattern with
      large regurgitant orifice. In patients with mitral prosthetic dehiscence with
      laminar flow pattern, transesophageal echocardiography can provide reliable
      diagnostic information.

PMID- 8252987
TI  - Chronic tension pneumothorax mimicking tension bullae. Use of video-assisted
      thoracoscopy for diagnosis.
AB  - A 48-year-old patient had a lucent right hemithorax and marked mediastinal shift
      of unknown duration that appeared on a chest radiograph. He was unchanged
      symptomatically from his baseline status. Video-assisted thoracoscopy was used to
      distinguish between tension from a giant bulla and a chronic tension
      pneumothorax.

PMID- 8252988
TI  - Central venous catheter migration to the popliteal artery during total
      cavopulmonary shunt.
AB  - Central venous catheter migration to the arterial system occurred due to the
      surgical procedure during total cavopulmonary shunt. The catheter seems to have
      crept into the portion of the vena cava that had been designated for clamping,
      because of the position for the surgery and the anatomic characteristics of the
      patient. The catheter migrated in the right popliteal artery and was removed
      immediately; however, it could enter the pulmonary arterial system and the other
      systemic arterial branches.

PMID- 8252989
TI  - Beguiled by the gallium. Thymic rebound in an adult after chemotherapy for
      Hodgkin's disease.
AB  - An 18-year-old woman was diagnosed as having Hodgkin's disease involving the
      mediastinal lymph nodes and lung parenchyma. A pretreatment gallium 67 scan
      showed increased uptake in the mediastinum. Chest radiograph and chest computed
      tomographic (CT) scans after chemotherapy demonstrated resolution of disease, and
      a repeated gallium scan was normal. Four months later, a surveillance gallium
      scan showed increased activity in the mediastinal and hilar regions with
      corresponding chest CT and magnetic resonance imaging (MRI) showing a
      retrosternal mass. Prior to committing the patient to aggressive treatment for
      presumed disease relapse, a biopsy of the mass was performed and a specimen
      showed normal thymus tissue. The patient has continued in remission without
      further therapy 3 years after her initial treatment, with subsequent normal
      gallium scans and a stable mass on CT and MRI. Thymic enlargement following
      chemotherapy can occur with Hodgkin's disease in young adults, and interpretation
      of imaging studies, including gallium scanning, must be made with this
      consideration in mind.

PMID- 8252990
TI  - Left lung asthma.
AB  - The chest radiograph of a woman with acute asthma showed signs of obstructive
      emphysema of the left lung. Fiberoptic bronchoscopy excluded obstruction of a
      large bronchus. The signs disappeared after antiasthmatic treatment, suggesting
      that they were caused by airway closure. In usual asthma, airway closure affects
      both lungs; the reason for the unilateral predominance we observed is unknown.

PMID- 8252991
TI  - Adult T-cell leukemia involving the central nervous system after remission of
      adult respiratory distress syndrome.
AB  - We report a rare case of adult T-cell leukemia (ATL) in which the patient had an
      acute type of ATL involving the central nervous system (CNS) after remission of
      adult respiratory distress syndrome (ARDS) due to human T lymphotropic virus type
      1 associated bronchopneumopathy. A 62-year-old woman was admitted to the hospital
      because of ARDS. Pulse therapy with methylprednisolone improved ARDS, but she
      fell into a coma due to ATL and CNS invasion 5 months after recovery. Although
      chemotherapy decreased the fraction of abnormal lymphocytes, her consciousness
      level did not improve and she died.

PMID- 8252992
TI  - Gaucher's disease. An unusual cause of intrathoracic extramedullary
      hematopoiesis.
AB  - A thoracic paravertebral mass in an asymptomatic woman with type 1 Gaucher's
      disease proved to be due to extramedullary hematopoiesis. This is, to our
      knowledge, the first case of intrathoracic extramedullary hematopoiesis reported
      with Gaucher's disease.

PMID- 8252993
TI  - Bronchiolitis obliterans organizing pneumonia associated with massive L
      tryptophan ingestion.
AB  - A 51-year-old woman developed acute febrile illness with respiratory failure
      following intake of L-tryptophan. An open lung biopsy specimen established the
      histopathologic nature of the lung lesion as bronchiolitis obliterans organizing
      pneumonia (BOOP). There was no evidence of other known causes usually associated
      with BOOP. Her condition improved with corticosteroid therapy. The entity of BOOP
      now should be added to the growing list of illnesses associated with the use of L
      tryptophan.

PMID- 8252994
TI  - Septic pulmonary embolism due to periodontal disease.
AB  - Three weeks following a toothache, a 56-year-old man developed cough, sputum,
      fever, and pleuritic chest pain. He had mild periodontal disease and his chest
      radiographs and chest computed tomographic (CT) scans showed multiple pulmonary
      nodules. The CT scan strongly suggested septic pulmonary embolism. Aspirated pus
      from one of the nodules yielded pure growth of Streptococcus intermedius. Lesions
      resolved with antimicrobial therapy. The usual predisposing factors for septic
      pulmonary embolism were absent, and, the isolation of S intermedius from the pus,
      the antecedent toothache, and periodontal disease all suggested the gingiva as
      the source. We hypothesize that periodontal infection led to bacteremia, seeding
      of the lungs, and multiple anaerobic pulmonary abscesses, akin to reported
      instances of infective endocarditis from dental foci without any prior dental
      procedures. To our knowledge, this presentation of septic pulmonary embolism is
      unprecedented.

PMID- 8252995
TI  - Simultaneous legionellosis and invasive aspergillosis in an immunocompetent
      patient newly treated with corticosteroids.
AB  - Invasive pulmonary aspergillosis (IPA), although unusual, has been recognized in
      the immunocompetent host. Several cases of IPA with rapidly progressive
      respiratory failure have been reported in patients receiving short-term
      corticosteroid therapy for chronic obstructive pulmonary disease. Atypical
      pneumonia caused by dual infection with Legionella pneumophila and Mycoplasma
      pneumoniae has also been reported. We report an unusual case of simultaneous L
      pneumophila pneumonia and IPA in an asthma patient with suspected allergic
      bronchopulmonary aspergillosis newly treated with corticosteroids.

PMID- 8252996
TI  - Resolution of coronary ischemic syndrome due to dislodgement of intraluminal
      thrombus during diagnostic cardiac catheterization.
AB  - Dislodgement of an intraluminal coronary thrombus occurred in a patient with
      unstable angina during diagnostic cardiac catheterization. The thrombus
      propagated into the systemic circulation without clinical manifestation of
      embolism. The procedure rendered the patient asymptomatic. The case illustrates
      the role of intraluminal coronary thrombus in unstable angina.

PMID- 8252997
TI  - Pulmonary metastatic disease in ameloblastoma.
AB  - Ameloblastoma is a rare disease of odontogenic origin with indeterminate
      metastatic potential. The first site of metastatic disease is usually the lung.
      We report aggressive surgical treatment of a patient with bilateral disease with
      five subsequent recurrences. A review of the literature suggests that in the
      absence of effective chemotherapy or radiation, surgery should be considered the
      treatment of choice for metastatic ameloblastoma confined to the lung.

PMID- 8252998
TI  - Prevention and treatment of glucocorticoid-induced osteoporosis.

PMID- 8252999
TI  - Pectin-induced occupational asthma.

PMID- 8253000
TI  - Rib biopsy.

PMID- 8253001
TI  - Diffusion capacity in heart transplant recipients.

PMID- 8253002
TI  - Antithrombotic therapy in atrial fibrillation.

PMID- 8253003
TI  - IgG subclass deficiency.

PMID- 8253004
TI  - Strictureplasty for ileocolic anastomotic strictures in Crohn's disease.
AB  - PURPOSE: Because of the limited experience, the use of strictureplasty for a
      strictured ileocolic anastomosis associated with Crohn's disease was reviewed.
      METHODS: We reviewed 22 patients who had a strictureplasty to treat symptomatic
      ileocolic anastomotic strictures related to Crohn's disease. The median interval
      between a previous ileocolic anastomosis and strictureplasty was 2 years (range,
      1 to 26 years). The median age was 39 years and there were 15 males and 7
      females. The median follow-up was 2 years. RESULTS: Strictureplasty on a
      strictured ileocolic anastomosis was either a Heineke-Mikulicz (n = 15) or a
      Finney (n = 7) strictureplasty. Fifteen (68 percent) patients needed 47
      additional strictureplasties in other sites of the small bowel and 5 (23 percent)
      patients had synchronous small bowel resection mainly for separate areas of
      phlegmonous disease. Only five (23 percent) patients did not have a synchronous
      procedure on the small bowel. There was no mortality or major septic
      complications. After surgery, relief of obstructive symptoms was noted in all
      patients. The median weight gain at six months after surgery was 3 kg (range, -5
      to +10 kg) and 75 percent of the patients were weaned off steroids. Symptomatic
      "recurrence" occurred in two (9 percent) patients from new strictures at sites
      unrelated to previous strictureplasties; only one needed reoperation for
      recurrence. Patency of the strictureplasty on ileocolic anastomosis in
      asymptomatic patients was confirmed by small bowel contrast study (n = 12) and
      colonoscopy (n = 4). CONCLUSIONS: Strictureplasty preserves small bowel length
      and may be a viable alternative to repeat ileocolic resection in suitable cases.

PMID- 8253005
TI  - Obstruction after ileal pouch-anal anastomosis: a preventable complication?
AB  - Small bowel obstruction is a common complication after ileal pouch-anal
      anastomosis. This review of 460 patients examines the frequency of small bowel
      obstruction and determines potential risk factors. The leading indication for
      ileal pouch-anal anastomosis was ulcerative colitis (83 percent). In 142 patients
      (31 percent), loop ileostomy was rotated 180 degrees to facilitate emptying of
      the ileostomy. Ninety-four patients (20 percent) had 109 episodes of obstruction.
      Obstruction occurred after creation of the pouch (40 episodes), closure of the
      ileostomy (29 episodes), or developed during the subsequent follow-up period (40
      episodes). Operative intervention was required in 39 percent of the episodes (7
      percent of all patients). At operation, the most common point of obstruction was
      at closure of the ileostomy (n = 22/42, 52 percent). In 16 of these patients, the
      ileostomy had been rotated. Multiple risk factors, including age, sex, primary
      diagnosis, surgeon incidence, pouch type, prior colectomy, steroid usage, stomal
      rotation, technique of closure of the ileostomy, and prior obstruction, were
      examined by univariate and multivariate analysis. Of all factors, only stomal
      rotation was statistically significant (P = 0.0005, chi-squared analysis).
      Rotation of the loop ileostomy during ileal pouch-anal anastomosis, although an
      apparent technical refinement, is unnecessary and predisposes to obstruction.

PMID- 8253006
TI  - Visceral neuropathy in slow transit constipation: an immunohistochemical
      investigation with monoclonal antibodies against neurofilament.
AB  - PURPOSE: The aim of this study was to investigate neuropathologic changes in the
      colonic wall of patients with slow transit constipation using monoclonal
      antibodies raised against neurofilament. METHODS: In a prospective study, 227
      patients with severe, long-standing constipation and intractable defection
      disorders were analyzed according to a standard protocol. Slow transit
      constipation was diagnosed in 65 patients (29 percent). Forty-three patients (7
      men and 36 women; mean age, 46 years; range, 16-76 years) underwent a partial (n
      = 20) or subtotal (n = 23) colectomy. In 39 patients (5 with megacolon and 34
      with normal-sized colon) the cause of their constipation remained unexplained
      (idiopathic slow transit constipation). All resected colon specimens were
      investigated with the monoclonal antineurofilament antibody NF2F11 and compared
      with those of 20 control patients. RESULTS: In all controls the myenteric plexus
      revealed a moderate and diffuse axonal staining. In 29 of 39 patients with
      "idiopathic" slow transit constipation, the apparently normal axon bundles in the
      myenteric plexus stained markedly less than normal or failed to stain at all with
      the monoclonal antibody. In 17 patients this reduced or absent neurofilament
      expression was found along the entire length of the colon, whereas in 12 patients
      only a portion of the colon was affected. CONCLUSION: These findings indicate
      that a visceral neuropathy seems to be present in the majority of patients with
      severe, so-called idiopathic slow transit constipation.

PMID- 8253007
TI  - Practice parameters for the treatment of hemorrhoids. The Standards Task Force
      American Society of Colon and Rectal Surgeons.
AB  - It should be recognized that these guidelines should not be deemed inclusive of
      all proper methods of care or exclusive of methods of care reasonably directed to
      obtaining the same results. The ultimate judgment regarding the propriety of any
      specific procedure must be made by the physician in light of all of the
      circumstances presented by the individual patient.

PMID- 8253008
TI  - Small rectosigmoid polyps as markers of proximal neoplasms.
AB  - PURPOSE: The aim of this study was to determine the spatial distribution and
      histotype of small colorectal polyps and to determine the validity of distal
      small colorectal polyps as markers of proximal neoplasms. METHODS: In 366
      patients who underwent total colonoscopy and removal of all polyps, the presence
      and features of polyps were recorded. The relationship between proximal neoplasms
      and distal polyps was investigated in 216 of 366 subjects who had no personal or
      familial history of colorectal neoplasia. RESULTS: Of 366 patients, 96 were free
      from polyps. A total of 733 small colorectal neoplasms was removed from the
      remainder: 79.9 percent neoplastic and 20.1 percent hyperplastic, inflammatory,
      or hamartomatous. High-grade dysplasia was noted in 2.7 percent of the neoplastic
      polyps. One adenoma containing invasive carcinoma was observed. In the subset of
      216 patients, proximal neoplasms were found in 11.4 percent of those with no
      distal polyps, 33.8 percent of those with distal-small colorectal polyps only (P
      < 0.01), and 58.8 percent of those with at least one polyp > 5 mm in diameter (P
      = 0.001). The proximal neoplasm percentage was the same in patients with at least
      one adenomatous-small polyp and those with only hyperplastic-small polyps.
      CONCLUSIONS: A distal-small colorectal polyp, whether adenomatous or
      hyperplastic, may be a proximal neoplasm marker. Total colonoscopy is thus
      justified in all patients with distal polyps, regardless of their size and
      histotype.

PMID- 8253009
TI  - Hemorrhage following colonoscopic polypectomy.
AB  - Clinically significant hemorrhage following colonoscopic polypectomy may occur
      primarily as the polyp is removed or manifest itself days to weeks later
      secondary to clot dissolution. The rate of hemorrhage following colonoscopic
      polypectomy ranges widely from 0.3 to 6.1 percent, depending on whether the data
      are derived from studies using the number of patients or number of polypectomies.
      A retrospective study was performed in our institution to study 4,721 patients
      who underwent polypectomy between January 1987 and December 1991. Twenty (0.4
      percent) of these patients required hospital admission because of 9 primary and
      11 delayed hemorrhages. Fifty-four polyps were removed from these patients: 11 in
      the right colon, 7 in the transverse colon, 17 in the descending colon, and 19 in
      the sigmoid colon. Eight polyps were 2 cm or larger, 10 were pedunculated, and 44
      were sessile. Six patients underwent cauterization or resnaring of the bleeding
      polyp site, one patient underwent subtotal colectomy, and the remainder of the
      patients stopped bleeding spontaneously. Factors that could be associated with
      the outcome of hemorrhage include patient age, size, location, number and
      morphology of polyps (i.e., sessile or thick stalk), and use of anticoagulants.
      An experienced endoscopist with knowledge of electrosurgical and technical
      principles may be the most important factor for prevention of postpolypectomy
      bleeding.

PMID- 8253010
TI  - Scintigraphic defecography: quantitative and dynamic assessment of anorectal
      function.
AB  - PURPOSE: Conventional assessment of anorectal function with defecating
      videoproctography is semiquantitative and the high radiation exposure precludes
      prolonged or repeated testing. The aim of this study was to develop a dynamic
      scintigraphic method of assessing anorectal function. METHODS: Fourteen patients
      with fecal incontinence, 18 patients with chronic constipation, and 8 control
      subjects were assessed by scintigraphic defecography. This involves introduction
      of a technetium-99m-radiolabeled artificial stool into the rectum of the subject
      and acquisition of gamma camera images during evacuation. RESULTS: Mean
      evacuation rate was 2.8 percent/second in incontinent patients and 0.9
      percent/second in constipated patients (P < 0.001). The mean anorectal angles
      were 136 degrees and 133 degrees, respectively. There were 18 cases of pelvic
      floor descent and 6 rectoceles. Scintigraphic defecography provides quantitative
      information on rectal evacuation. Anorectal angle and pelvic floor movement can
      be examined. The radiation dose to pelvic organs is significantly less than with
      videoproctography. CONCLUSION: We believe that scintigraphic defecography is the
      investigation of choice for objective and dynamic assessment of anorectal
      function.

PMID- 8253011
TI  - Ileosigmoid knotting in Turkey. Review of 68 cases.
AB  - PURPOSE: The high mortality associated with ileosigmoid knotting prompted us to
      review the collected experiences of three university hospitals in order to
      establish a more rational approach to the problem. METHOD: The clinical records
      of 68 patients with ileosigmoid knotting from 1970 to 1990 were reviewed with
      respect to incidence, etiopathogenesis, clinical features, treatment, and
      clinical outcome. RESULTS: The most common type of ileosigmoid knotting was Type
      IA (48.5 percent), in which the active ileum encircled the passive sigmoid in a
      clockwise manner. Fifty (73.5 percent) patients developed a gangrenous bowel
      whereas 18 patients did not show any definite evidence of impairment of bowel
      viability. En bloc removal of gangrenous knot and reestablishment of intestinal
      continuity by enteroenteric or enterocolic anastomosis combined with the Hartmann
      procedure, which was employed in 20 (42.6 percent) cases, constituted the most
      frequently preferred operation. The mortality rate in this series was 30.9
      percent (21/68) and toxic shock, which ultimately resulted in multiple organ
      failure, was the major cause of death. It was remarkable to note that there was
      an inverse correlation between the duration of symptoms and the mortality rate
      reflecting the dramatic rapidity and severity of symptoms due to tightness of the
      knot which led to early and extensive gangrene, thus inevitably urged the
      patients to seek medical help without delay. CONCLUSION: The performance of
      prompt, individualized surgical treatment in conjunction with the use of advanced
      measures of critical care to combat the disastrous consequences of multiple organ
      failure would contribute greatly to improve survival rate in victims of this
      dreadful entity.

PMID- 8253012
TI  - Effect of prostaglandin E1 and steroid on healing colonic anastomoses.
AB  - PURPOSE: The effect of prostaglandin E1 (PGE1) and corticosteroids alone and in
      combination were studied in the healing rat colon to determine whether PGE1 could
      not only improve healing but reverse the negative effect of steroids on colonic
      wound healing. METHODS: Colonic anastomoses were performed in 144 male Sprague
      Dawley rats divided into four groups. The control group (I) received no further
      treatment. The steroid group (II) received cortisone acetate (5 mg/kg/day)
      beginning six days preoperatively and continuing until sacrifice. The PGE1 group
      (III) received 2 micrograms of PGE1 intra-aortically at surgery and for three
      days postoperatively. The combination PGE1/steroid group (IV) received both drugs
      in the same doses as those in Groups II and III. Animals were sacrificed on
      postoperative days 6, 10, and 14. Wound healing was evaluated by hydroxyproline
      content, bursting pressures, and histology. RESULTS: The hydroxyproline assay at
      day 10 revealed that steroid-treated rats have significantly lower levels than
      any other group. The PGE1 group (III) had the highest level of significance in
      comparison to the steroid group (II) (P = 0.001). The addition of PGE1 to steroid
      (Group IV) appeared to abolish the negative effect of the steroid as measured by
      hydroxyproline content on day 10 (P = 0.038). When measuring bursting pressures,
      the PGE1 group (III) had significantly higher pressures than any other group at
      day 10. However, no amelioration of the steroid effect on bursting pressures was
      seen. Histologic evaluation of the anastomosis did not reveal any significant
      differences among the four groups. CONCLUSIONS: PGE1 reverses the negative effect
      of the steroid on hydroxyproline levels at day 10. Furthermore, using bursting
      pressure as a parameter of wound healing, administration of PGE1 results in
      significantly improved anastomotic healing at day 10.

PMID- 8253013
TI  - Human monoclonal antibody SK1-mediated cytotoxicity against colon cancer cells.
AB  - PURPOSE: Human monoclonal antibody (HuMAb) SK1, a human monoclonal IgM, has
      previously been shown to react selectively with a wide range of human carcinomas.
      In this study, the complement-dependent cytotoxicity (CDC) mediated by the HuMAb
      SK1 was investigated. METHODS: The presence of AgSK1 on the two studied cell
      lines, HT29 and PANC-1, was evaluated by the immunocytochemical staining. The
      intracellular and surface locations of the targeting antigen of HuMAb SK1 were
      further characterized by the study of flow cytometry. The specific lysis of
      target cells by the HuMAb SK1 in the CDC assay was studied. RESULTS: In the
      presence of human complement, the HuMAb SK1 was shown to be effective in the
      lysis of cultured human gastrointestinal cancer cells as well as the fresh colon
      cancer cells derived from the patient's specimens. In addition, our data
      suggested that HuMAb SK1 activated the mouse complement in a similar magnitude.
      CONCLUSIONS: We concluded that HuMAb SK1 showed some promise for future clinical
      trials. The in vitro CDC effect of HuMAb SK1 with mouse complement suggested that
      the antitumor effect of HuMAb SK1 might be successfully studied in the nude mouse
      model bearing xenografts of human colon cancer as a part of the preclinical
      evaluation.

PMID- 8253014
TI  - Anal endosonography for recurrent anal fistulas: image enhancement with hydrogen
      peroxide.
AB  - Anal endosonography is a new technique that is useful in the preoperative
      assessment of patients with anal fistulas. Endosonographic images are created by
      the reflection of sound waves from the interfaces between tissues of varying
      densities. In order to accentuate tissue interface layers at the level of the
      fistula tract, we introduced hydrogen peroxide into the fistula tract through the
      external opening during anal ultrasonography in two patients with recurrent anal
      fistula. Hydrogen peroxide injection resulted in hyperechoic imaging of the
      preinjection hypoechoic horseshoe fistula tract. Endosonographic findings were
      confirmed at the time of surgery in both patients. We conclude that hydrogen
      peroxide enhancement of the fistula tract is a simple, effective, and safe method
      of improving the accuracy of endoanal ultrasound assessment of recurrent anal
      fistula.

PMID- 8253015
TI  - Can assessment of IDDM risk in siblings be improved?

PMID- 8253016
TI  - Epidermal growth factor in mammary glands and milk from rats: the influence of
      insulin.
AB  - Epidermal growth factor (EGF) is one of the major growth-promoting agents in
      milk. Using immunohistochemistry we localized EGF in the mammary glands of
      lactating rats to the luminal border of the secretory cells. Following
      proteolytic pretreatment of the histological sections, the EGF-immunoreactivity
      was revealed homogeneously in the cytoplasm of the secretory cells, which might
      suggest that EGF is present as a precursor molecule in the mammary glands.
      Altered glucose metabolism during lactation results in secondary hypoinsulinaemia
      in the lactating rat. As insulin is also known to affect lactation in several
      species, we treated normal lactating rats daily with insulin and studied the
      effect on the composition of milk. A significant increase in the content of total
      protein and milk fat was observed after a few days of insulin-treatment, as
      compared to a control group [total protein: 50 (36-97) g/l vs. 42 (35-72) g/l],
      [milk fat: 35 (22-40)% vs. 29 (23-36)%], [median (range)]. On day 16 the EGF
      concentration in milk was significantly increased in insulin-treated rats, as
      compared to controls [2.66 (1.40-5.08) nM vs. 1.98 (1.04-3.16) nM]. A similar
      significant increase was found for the secretion of the cobalamin-binding
      protein, haptocorrin (HC) [37.7 (15.8-110.4) nM vs. 23.5 (15.5-70.1) nM]. In
      conclusion, the highly insulin-sensitive lactating mammary glands were affected
      by exogenous insulin, since the milk concentrations of EGF, HC, total protein and
      the fat percentage were increased.

PMID- 8253017
TI  - Insulin autoantibodies and immune response to human insulin therapy in 24 type 1
      (insulin-dependent) diabetic children: superiority of radio binding assay over
      solid phase assay.
AB  - To evaluate the immunization pattern against human insulin, 24 newly diagnosed
      diabetic children (12 females, 12 males; mean age: 7 +/- 4 years) were treated
      from diagnosis onwards with semisynthetic human insulin (NOVO). Informed consent
      was obtained from all parents. Blood samples were taken before, 1, 2, 3, 4, 6 and
      8 weeks after the start of therapy and, thereafter, at monthly intervals for 2
      years. Insulin (auto) antibodies (I(A)A) were measured by radio binding assay
      (RBA) and by enzyme-linked immunosorbent assay (ELISA). IAA, determined by RBA,
      were detected in eight children. Using ELISA, IgM IA were not detected after
      onset of therapy. By contrast, IgG IA were found in 8 children after 2 weeks of
      treatment and in 12 after 1 month. Using RBA, all children had IA after 2 months
      of therapy, whereas with ELISA, IA remained undetectable during the study period
      in 8 out of 24 patients. These results confirm previous observations suggesting
      that the 2 methods are not interchangeable and yield different estimations of the
      insulin immune reaction, not only before but also after the start of insulin
      therapy. In addition, the detection of IA by RBA in all treated patients
      unambiguously demonstrates that human insulin is immunogenic in man.

PMID- 8253018
TI  - Detection of heat shock protein in patients with insulin-dependent diabetes
      mellitus.
AB  - We have investigated whether antibodies to heat shock protein (hsp) 65 are
      present in sera from patients with insulin-dependent diabetes mellitus by using
      Mycobacterium leprae hsp65. Fifty-two sera from patients with IDDM, 36 from
      patients with unclassified insulin-treated diabetes mellitus and 41 from normal
      healthy controls were examined by ELISA assay. Seventeen (32.7%) out of 52 IDDM
      sera and 10 (27.8%) out of unclassified insulin-treated diabetic sera were
      positive for anti-Mycobacterium (anti-M. leprae) hsp65 antibodies while none of
      the healthy control sera were positive. Based on western blot analysis, 12 of the
      17 IDDM sera and 1 of 2 sera from the unclassified insulin-treated diabetics were
      positive for anti-M.leprae hsp65 antibodies while all normal control sera were
      negative. These results support the idea that hsp65 may play a role in the
      pathogenesis of IDDM. Future studies are necessary to elucidate the role of hsp65
      in the pathogenesis of IDDM.

PMID- 8253019
TI  - Decreased weight gain in BB rats before the clinical onset of insulin-dependent
      diabetes.
AB  - Inbred specific pathogen-free diabetes-prone (DP) and diabetes-resistant (DR) BB
      rats were crossed to produce F1 and intercrossed to produce F2 rats. Diabetes
      segregates in these crosses as a recessive trait on rat chromosome 4. The weight
      gain of genetically diabetes-prone rats born to F1 healthy parents was studied to
      avoid effects of maternal diabetes. The weight gain of the F2 rats was initially
      not different from the F1 parents. The F2 rats later developing diabetes grew in
      parallel with their non-affected siblings up until the last 9 days before onset.
      During these 9 days they showed a decreased weight gain compared to their healthy
      litter-mates regardless of age. We conclude that decreased weight gain precedes
      the abrupt clinical onset of diabetes in BB rats and that it may be due to
      processes associated with the selective loss of beta cells.

PMID- 8253020
TI  - Outcome of pregnant diabetic patients in Benghazi (Libya) from 1984 to 1991.
AB  - During the period from 1 June 1984 to 1 June 1991, 988 pregnant diabetic patients
      were treated by a team of physicians and obstetricians in Benghazi Diabetic
      Clinic. Twelve patients were insulin-dependent (type 1) and 976 patients were non
      insulin-dependent (type 2). Ninety patients were diagnosed for the first time
      during pregnancy. Thirty-nine patients defaulted. Eight hundred and seventy-six
      patients were treated with insulin and 112 patients were controlled by diet. The
      average daily insulin dose was 40.12 units. The majority, 64.5%, delivered
      vaginally and 35.5% by caesarean section. Rates of abortion, intra-uterine death
      and still birth were 7.99%, 3.28% and 2.6%, respectively. The mean birth weight
      was 3.78 +/- 0.89 kg. Congenital anomalies of infants were 3.4%. Perinatal
      morality was 11.44%. Poor metabolic control has been associated with increased
      rates of abortion, intra-uterine death and congenital anomalies. It was concluded
      that team approach and multiple insulin injections could improve the outcome of
      pregnancy in developing countries to near current western standards.

PMID- 8253021
TI  - The diabetic foot. General considerations and proposal of a new therapeutic and
      preventive approach.
AB  - The treatment of the diabetic foot is a common and sometimes difficult problem.
      The treatment of the characteristic lesions of the diabetic foot involves many
      forms of therapy: these include contact dressings and topical treatments. The
      different therapies that have been applied do not often give satisfactory
      results. Therefore, for this purpose, we have studied the effect of
      biostimulation of wound-healing by utilising the CO2 laser together with the
      action of the KTP laser on 25 patients (11 females and 14 males), all suffering
      from diabetes mellitus with polyneuropathic ulcers of the foot. Low out-put laser
      irradiation may stimulate granulation tissue and collagen production in
      fibroblasts. Many studies observed a regeneration of microcirculation in the
      ulcer and a regeneration of lymphatic circulation. The laser irradiation method
      produces a sterilizing effect from bacteria that over-infect the diabetic ulcer
      too. Each patient underwent a surgical treatment of the edges of the ulcers with
      CO2 and KTP laser (wavelength 532 nm) focused, and a combined phototherapy (CO2
      laser and afterwards KTP laser, defocused). The irradiation was carried out
      through laser beam (by optic fiber for KTP) manually directed, until all of the
      ulcer surface became irradiated. On the skin around the ulcer, an omental derived
      cream (fractionated porcine omental lipid extracts) was daily applied,
      independently from the laser treatment, to evaluate the angiogenic effect of this
      substance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253022
TI  - The effect of a heparin analogue, ITF-5005, on diabetes incidence and insulitis
      in the non-obese diabetic mouse.
AB  - It has been suggested that heparin and its analogues may have a suppressive
      effect on the immune response by interfering with T-lymphocyte heparinase
      activity, thus altering the ability of T-lymphocytes to penetrate the
      extracellular matrix and migrate to target tissues. We have investigated whether
      a heparin analogue (ITF-5005) can alter lymphocytic infiltration of the endocrine
      pancreas (insulitis) and/or diabetes incidence in the non-obese diabetic (NOD)
      mouse. Sixty-four NOD mice were divided at weaning and injected subcutaneously
      five times per week with either 18, 36 or 72 micrograms/kg body weight of ITF
      5005 or saline as a control. At 12 weeks of age, the animals were culled and
      their pancreata sectioned, stained and assessed 'blind' for insulitis and insulin
      containing cells. Insulitis was similar in all groups as was the proportion of
      insulin-containing cells. To determine the effect on diabetes incidence, two
      groups of mice were injected with either saline or 140 micrograms/kg body weight
      of ITF-5005 from weaning until 30 weeks of age. No difference was found in
      overall diabetes incidence; however, disease onset was significantly accelerated
      in the treated group. We conclude that ITF-5005, at the doses employed, has no
      effect on insulitis or the proportion of treated group. We conclude that ITF
      5005, at the doses employed, has no effect on insulitis or the proportion of
      insulin-containing cells found in the pancreas, but that it can accelerate the
      course of diabetes in the NOD mouse.

PMID- 8253023
TI  - Self-monitoring of blood glucose and insulin dose alteration in type 1 diabetes
      mellitus.
AB  - The purpose of this study was to evaluate the relationship between proper use of
      self-monitoring of blood glucose (SMBG) including knowledge and application of
      specific algorithms and metabolic control in a group of randomly selected insulin
      dependent diabetic patients. We studied 80 patients responding to the following
      criteria: intensive conventional insulin therapy and SMBG for at least 6 months
      using a reflectance meter, and previous 5-day hospital education period. The
      practical knowledge of the guidelines was evaluated by a questionnaire simulating
      8 metabolic situations. A computer analysis of the SMBG data for the 3 months
      preceding the study allowed us to evaluate patient compliance with SMBG (number
      of blood glucose determinations) and patients' application of the guidelines
      (percentage of insulin doses modified according to the guidelines). Fifty-nine
      patients (79%) were compliant with SMBG and had better metabolic control than the
      non-compliers (HbA1c: 6.7 +/- 1.1% vs. 7.5 +/- 1.9, P < 0.05). Twenty-eight out
      of the 59 compliant subjects had good knowledge of the guidelines but without
      patent improvement of glycemic control. Seventeen of these 28 correctly used the
      algorithms to modify insulin dosage; their HbA1c levels were lower than those of
      the 11 patients who did not use the algorithms (6.1 +/- 0.9 vs. 7.1 +/- 0.9%, P <
      0.05). The percentage of insulin dose modification consistent with the guidelines
      and the level of HbA1c was negatively correlated in the good-knowledge group. The
      conclusion is that good metabolic control is linked not only with the degree of
      knowledge but also with the application of this knowledge.

PMID- 8253024
TI  - Relationship between urinary excretion of fibronectin degradation products and
      proteinuria in diabetic patients, and their suppression after continuous
      subcutaneous heparin infusion.
AB  - To explore the possibility that the excretion of urinary fibronectin degradation
      products (U-FnDP) can be an indicator of the progression of diabetic nephropathy,
      U-FnDP and urinary protein(U-P) were determined in 64 diabetic patients and 11
      healthy volunteers. Moreover, to determine whether continuous subcutaneous
      heparin infusion (CSHI) reduces elevated U-FnDP and U-P in diabetic patients with
      persistent proteinuria, heparin sodium was administered as a bolus subcutaneous
      injection of 5000 IU, followed by subcutaneous infusion of 250 IU/kg per 24 h
      heparin sodium for 7 days. U-FnDP excretion rate elevated proportionally to the
      degree of U-P. CSHI reduced significantly elevated U-FnDP from 172.68 +/- 15.79
      to 100.04 +/- 14.93 micrograms/24 h (P < 0.01) and U-P from 1.76 +/- 0.13 to 1.20
      +/- 0.12 g/24 h (P < 0.01). No significant changes in blood pressure and diurnal
      mean plasma glucose levels were found. APTT was prolonged with a decrease of AT
      III activity during the treatment. These findings suggest that U-FnDP can be one
      of the indicators which reflects the degree of progression of diabetic
      nephropathy, and that CSHI may be useful for the normalization of elevated U-FnDP
      and reduction in U-P in diabetic nephropathy.

PMID- 8253025
TI  - The prevalence of diabetes mellitus and impaired glucose tolerance among Hong
      Kong Chinese adults of working age.
AB  - We studied 1513 employees (910 men and 603 women) from a public utility company
      and a regional hospital to document the prevalence of diabetes mellitus (DM) and
      impaired glucose tolerance (IGT) in the Chinese working population of Hong Kong
      using a 75-g oral glucose tolerance test and World Health Organisation (1985)
      criteria. The overall prevalence of DM was 4.5 (95% confidence interval: 3.5
      5.7%) and that of IGT 7.3 (6.0-8.6%). The prevalence of DM was 5.1 (3.7-6.5%) in
      men and 3.6 (2.1-5.1%) in women, while that of IGT was 7.4 (5.7-6.5%) in men and
      7.1 (5.1-9.1%) in women. The truncated age-adjusted rate of DM for age 30-64 is
      7.7% which is comparable to the age-adjusted prevalence rates among Chinese
      living in Singapore and Mauritius but in marked contrast to the low prevalence
      rate in Chinese living in Mainland China. Among the diabetic subjects, 38.2% had
      been previously diagnosed and 32% gave a family history affecting at least one
      first degree relative. Using polychotomous logistic regression analysis, the
      independent predictive factors for the development of DM include age (t = 7.31, P
      < 0.001), family history (t = 5.1, P < 0.001), waist hip ratio (t = 4.05, P <
      0.001) and body mass index (t = 4.62, P < 0.001). Our data further confirm that
      Hong Kong Chinese have a moderate to high susceptibility to non-insulin-dependent
      diabetes (NIDDM) when exposed to sufficient environmental and lifestyle factors.
      The high prevalence of IGT indicates a potential for the prevalence of DM to
      continue to rise unless effective preventive measures are implemented.

PMID- 8253026
TI  - Different rates of conversion to IDDM in siblings of type 1 diabetic children:
      the Montreal family study.
AB  - This study was undertaken to analyze the risk of developing insulin-dependent
      diabetes (IDDM) in siblings of type 1 diabetic children. Islet-cell antibodies
      (ICA) were tested in 568 subjects, siblings of type 1 diabetic children. The
      subjects were followed prospectively for the conversion to clinical diagnosis of
      IDDM. As a result siblings who were islet cell antibody (ICA)+ positive at the
      time of diagnosis of the diabetic sibling (index case) had a significantly higher
      risk of developing IDDM than those who were ICA-. However, of the 19 siblings who
      developed IDDM, only 10 were ICA+ at the time of the first test but, 17 became
      ICA+ before diagnosis of IDDM. The interval between a positive test and the
      clinical diagnosis of IDDM varied between subjects (6-44 months, mean = 18.4 +/-
      4.2 S.E. months) but it was less than 1 year in one subject. In addition to the
      higher risk of developing IDDM when ICA was positive, male sex and younger age of
      the subjects as well as young age of the index case and multiplex pedigrees were
      significant predictors of conversion to IDDM. The Cox's regression tree
      constructed using RECPAM identified three groups of varying rates of conversion
      to IDDM: (1) a group with the slowest progression characterized by ICA- and age
      of index case > 5 years or female sex (relative hazard = 1); (2) an intermediate
      progression group consisting of subjects who are ICA- and have both < 5 years of
      age and male sex (relative hazard = 8.78); (3) a group with the fastest
      progression consisting of subjects who are ICA+ (relative hazard = 31.45). From
      these results our data suggest that in addition to ICA, clinical markers such as
      age, sex and multiple pedigrees are also significant predictors of the rate of
      conversion to IDDM. Furthermore, screening for ICA in family intervention studies
      will have to be done frequently, perhaps yearly, and will have to be continued
      into adult life, particularly in ICA- subjects in order to identify the 85-90% of
      subjects who become ICA+ at the clinical diagnosis of IDDM.

PMID- 8253027
TI  - [The content of asbestos bodies in the bronchoalveolar fluid as a parameter of an
      increased pulmonary asbestos load].
AB  - Pulmonary asbestos burdens are usually determined by quantitative pulmonary dust
      analysis. The aim of this study was to investigate the value of bronchoalveolar
      lavage (BAL) for this purpose. First, the upper limit of normal for asbestos
      bodies (AB) in BAL fluid was established using a reference group of 371 patients
      with no evidence of increased exposure to asbestos. 99% of these patients had
      less than 0.5 AB/ml. In order to see whether BAL fluid AB concentration reflected
      pulmonary tissue content, BAL fluid and lung tissue from a further 64 patients
      with diverse histories of asbestos exposure were investigated. There was a
      positive association between AB concentration in BAL fluid and lung tissue only
      for the overall group of 64 patients (r = 0.86; P < 0.001). Twelve of 13 patients
      with more than 1 AB/ml and ten patients with more than 5 AB/ml had more than 1000
      AB/cm3 lung tissue, a value that is usually exceeded in asbestosis. When the
      upper concentration limit was set at 0.5 AB/ml for BAL fluid and 50 AB/cm3 for
      lung tissue, only two out of 64 patients had a false positive value (specificity
      95%), but eleven patients had false negative results (sensitivity 58%). These
      investigations establish that concentrations of > or = 0.5 AB/ml are a reliable
      indicator of increased asbestos exposure and concentrations > 1 AB/ml are
      associated with a higher probability of having more than 1000 AB/cm3 lung tissue.
      However, exclusion of increased asbestos exposure is not possible on the basis of
      negative BAL findings, since the sensitivity of the method is too low.

PMID- 8253028
TI  - [The use of a percutaneously connected heart-lung machine during resuscitation in
      cardiogenic shock after acute myocardial infarct].
AB  - A 47-year-old man was referred by an emergency physician to the intensive care
      unit of a hospital under resuscitation conditions while having recurrent attacks
      of ventricular fibrillation. Coronary angiography, performed while resuscitation
      measures had to be maintained, revealed severe three-vessel disease with
      occlusion of the anterior interventricular branch at its origin. Electrical and
      haemodynamic instability persisted even after thrombolysis with urokinase and
      introduction of an intraaortic balloon pump. Percutaneous partial cardiopulmonary
      bypass (CPB) was, therefore, instituted and a cardiac output of 2.5 1 achieved
      together with a stable sinus rhythm and a systolic pressure of 60-80 mm Hg. After
      9 h on CPB, drug administration could be levelled off and he was mobilised. He
      showed no neurological deficits and 4 months later he underwent an elective
      coronary bypass operation. This report demonstrates that even in conditions of
      resuscitation mechanical circulatory support can be undertaken rapidly and
      successfully, in the face of electrical instability, to achieve at least
      temporarily a stable circulation.

PMID- 8253029
TI  - [Retroperitoneal fibrosis].
AB  - A 53-year-old man without previous significant illness developed severe backache.
      Neither physiotherapy nor nonsteroidal anti-inflammatory drugs improved his
      condition so that he had been regularly taking pain-killing medication. 6 months
      later elevated retention values were detected and the patient was admitted to
      hospital. On admission the erythrocyte sedimentation rate (ESR) was markedly
      elevated in the presence of a normocytic anaemia, serum creatinine concentration
      of 3.71 mg/dl (blood urea of 112 mg/dl) and haematuria. Sonography demonstrated
      bilateral hydronephrosis, stage III, and a weekly echogenic para-aortic mass.
      Abdominal computed tomography showed a half-moon-shaped density anterior to the
      aorta. The middle segments of both ureters were displaced medially and the
      proximal parts dilated. Other causes (tumour, drug therapy, inflammation) having
      been largely excluded, idiopathic retroperitoneal fibrosis was diagnosed. The
      marked urinary obstruction necessitated the implantation of double-J-stents.
      Immunosuppressive treatment was started with daily 150 mg azathioprine and,
      initially, 50 mg prednisone. Within one week the serum creatinine concentration
      and ESR had fallen and the signs of urinary obstruction regressed.

PMID- 8253030
TI  - [The diagnosis of primary pulmonary hypertension].

PMID- 8253031
TI  - [The therapy of chronic heart failure with vasodilators. The development of a
      successful treatment principle].

PMID- 8253032
TI  - [The revocation of the authorization for preventive examinations in occupational
      medicine through the trade union].

PMID- 8253033
TI  - [Infection susceptibility in women].

PMID- 8253034
TI  - [Helicobacter pylori infection and peptic ulcer].

PMID- 8253035
TI  - [Helicobacter pylori infection and peptic ulcer].

PMID- 8253036
TI  - [Increased asthma mortality with the chronic use of beta-agonists?].

PMID- 8253037
TI  - [Mercury sensitization with amalgam fillings].

PMID- 8253038
TI  - [Fatal complication of a colonic contrast enema].

PMID- 8253039
TI  - [Digoxin in chronic heart failure].

PMID- 8253040
TI  - [The evaluation of perinatal mortality rates].

PMID- 8253041
TI  - [Magnetic resonance imaging in perianal Crohn's disease].
AB  - Magnetic resonance imaging (MRI) was undertaken in a prospective study of 34
      consecutive patients (21 women, 13 men; median age 31 [18-53] years) suspected of
      having active perianal Crohn's disease. The results of the investigation were
      compared with those obtained by independent observers on proctological and
      intraoperative examination (n = 31). A total of 58 fistulas and 21 abscesses were
      noted intraoperatively, 47 fistulas and all 21 abscesses by MRI, and 40 fistulas
      and 13 abscesses proctologically. The proctological examination proved to be more
      sensitive in demonstrating short subcutaneous or anovaginal fistulas (three of
      four subcutaneous and two of five anovaginal fistulas were not shown by MRI).
      Intersphincteric, ischiorectal and supralevator involvement was shown better by
      MRI. These results indicate that in perianal Crohn's disease MRI is a useful
      addition to proctological examination.

PMID- 8253042
TI  - [Involvement of the lungs in neurofibromatosis].
AB  - Two patients, a 66-year-old man (case 1) and a 55-year-old woman (case 2), had
      been known (for 40 and 35 years, respectively) to have type 1 neurofibromatosis.
      Dyspnoea, recently even at rest, had developed in both over the past few years.
      Both were emaciated (weight 62 kg, height 180 cm; 42 kg, 166 cm, respectively).
      In both the chest radiography had net-like increased interstitial markings.
      Computed tomography in case 1 showed largely subpleural small-blister-like
      changes bilaterally (honeycomb lung), while there were large apical cysts
      bilaterally in case 2. Lung function tests demonstrated restrictive changes in
      case 1 (vital capacity 48% of norm, relative one-second capacity 88%) and severe
      ventilation abnormality in case 2 (vital capacity 42% of norm, relative one
      second capacity 47%). Both had marked hypoxaemia even at rest and the walking
      limit was 200 m in case 1, 40 m in case 2. The pulmonary changes were most likely
      manifestations of the neurofibromatosis. Symptomatic treatment consisted of long
      term oxygen therapy with a portable liquid oxygen system (flow rate: 1-2 l/min at
      rest and 3-5 l/min on exercise; duration: 24 h/d). This achieved a walking
      distance without hypoxaemia of 500 and 200 m, respectively, with marked
      improvement in the patients' condition.

PMID- 8253043
TI  - [Successful lysis therapy in acute unilateral renal vein thrombosis].
AB  - A nephrotic syndrome developed in a 50-year-old man who, because of rheumatoid
      arthritis for the last three years, had been receiving gold therapy (30-50 mg
      sodium aurothiomalate weekly for 10 months). Treatment for the nephrotic syndrome
      was initiated with 100 mg prednisone daily. Ten days later he complained of
      severe pain in his right flank and haematuria was noted. Serum creatinine
      concentration increased from 1.0 to 1.8 mg/dl, while creatinine clearance fell to
      62 ml/min. Computed tomography demonstrated significant enlargement of the right
      kidney and a thrombus in the right renal vein which extended cranial into the
      inferior vena cava. High dosage infusion of urokinase (4.5-7.5 mill. IU daily for
      nine days) achieved complete lysis of the thrombus. The creatinine concentration
      fell to 1.1 mg/dl, while creatinine clearance rose to 104 ml/min. On the 5th day
      the right kidney had 25% of total function, several days later 40%.--This case
      illustrates that, as long as there are no contraindications, adequately high
      doses of urokinase can be appropriate treatment of acute renal vein thrombosis
      associated with the nephrotic syndrome.

PMID- 8253044
TI  - [Therapy of primary pulmonary hypertension].

PMID- 8253045
TI  - [Diagnosis and therapy of congenital toxoplasmosis].

PMID- 8253046
TI  - [Acyclovir].

PMID- 8253047
TI  - [alpha 1-antitrypsin deficiency and liver diseases].

PMID- 8253048
TI  - [Anticoagulation following stroke].

PMID- 8253049
TI  - [Hilum amputation].

PMID- 8253050
TI  - [Juvenile stroke and protein-S deficiency].

PMID- 8253051
TI  - [Autologous blood transfusion].

PMID- 8253052
TI  - A site accessible to extracellular TEA+ and K+ influences intracellular Mg2+
      block of cloned potassium channels.
AB  - The members of the RCK family of cloned voltage-dependent K+ channels are quite
      homologous in primary structure, but they are highly diverse in functional
      properties. RCK4 channels differ from RCK1 and RCK2 channels in inactivation and
      permeation properties, the sensitivity to external TEA, and to current modulation
      by external K+ ions. Here we show several other interesting differences: While
      RCK1 and RCK2 are blocked in a voltage and concentration dependent manner by
      internal Mg2+ ions, RCK4 is only weakly blocked at very high potentials. The
      single-channel current-voltage relations of RCK4 are rather linear while RCK2
      exhibits an inwardly rectifying single-channel current in symmetrical K+
      solutions. The deactivation of the channels, measured by tail current protocols,
      is faster in RCK4 by a factor of two compared with RCK2. In a search for the
      structural motif responsible for these differences, point mutants creating
      homology between RCK2 and RCK4 in the pore region were tested. The single-point
      mutant K533Y in the background of RCK4 conferred the properties of Mg2+ block,
      tail current kinetics, and inward ion permeation of RCK2 to RCK4. This mutant was
      previously shown to be responsible for the alterations in external TEA
      sensitivity and channel regulation by external K+ ions. Thus, this residue is
      expected to be located at the external side of the pore entrance. The data are
      consistent with the idea that the mutation alters the channel occupancy by K+ and
      thereby indirectly affects internal Mg2+ block and channel closing.

PMID- 8253053
TI  - Fourier transform infrared spectroscopic study of ion binding and intramolecular
      interactions in the polar head of digalactosyldiacylglycerol.
AB  - Lipid bilayers composed of digalactosyldiacylglycerol (DGDG), that is, Galp alpha
      1-6Galp beta 1-3DAG, a non-ionic lipid of the thylakoid membrane of chloroplasts,
      aggregate in aqueous media containing mono- and divalent cations in amounts above
      a threshold concentration (Ct) of about 1.0, 4.7 and 10.0 mM for Ca2+, Mg2+ and
      Na+, respectively. In this work, we found that above Ct the DGDG membranes do not
      undergo fusion and that the aggregation can be reversed or disrupted. This means
      that the perturbation induced by the salts results from adsorption, or
      complexation of the ions in the polar head of DGDG. To investigate this question,
      we used Fourier transform infrared (FTIR) spectroscopy to identify the molecular
      sites in DGDG which are modified by interaction, or adduct formation with CaCl2,
      MgCl2 and NaCl. We also determined whether the ions affect the intramolecular
      hydrogen bonding between the sn2 ester C = O and the carbon-6 of the alpha-anomer
      of galactose (Gal). The major conclusions are: (i) the salts do not affect, at
      least directly, the ester carbonyl region of DGDG, (ii) the most probable sites
      of binding, or adsorption, for the ions are the ring oxygen, and (iii) the ring
      hydroxyls are the sites of either ion complexation or intra- and intermolecular H
      bonding in interacting DGDG membranes. Within this framework, the complexation of
      the ions with Gal might induce total or partial dehydration of the galactolipid
      headgroup and thus provides the means to overcome the repulsive hydration forces
      that hinder aggregation of the DGDG membranes.

PMID- 8253054
TI  - Solvent modulation of the structural heterogeneity in FeIII myoglobin samples: a
      low temperature EPR investigation.
AB  - High spin FeIII myoglobin samples in solutions with different solvent composition
      have been investigated at low temperature by Electron Paramagnetic Resonance
      spectroscopy. The g = 6 line of the spectrum has been analyzed in terms of a
      distribution of the two crystal field parameters delta 1 and delta 2. By means of
      the Angular Overlap Method, it has been shown that these distributions entail, in
      turn, a distribution in the iron-heme displacement along the normal to the heme
      plane. The spread in this iron-heme distance, which can be connected with the
      binding action of the proximal histidine, has been proposed as a quantitative
      measurement of the structural heterogeneity (conformational substate landscape)
      displayed by the protein molecules. The results point out, moreover, that the
      solvent composition can affect the structural heterogeneity of the protein
      system. In particular, addition of glycerol, ethylene glycol and sucrose yields a
      significant reduction in the spread of the iron-heme displacement, while the
      presence of ammonium sulfate induces a change in the average position of the iron
      in the heme-plane. The role played by the solvent in the structure and dynamics
      of the protein, in connection also with the conformational substate distribution,
      is discussed.

PMID- 8253055
TI  - Flexoelectric effects in model and native membranes containing ion channels.
AB  - An experimental study of flexoelectricity in model membranes containing ion pores
      and native membranes containing ion channels has been undertaken with the
      objective of determining the relationship, if any, between flexoelectricity and
      ion transport. Model membrane patches containing ion pores induced by a blue
      green algal toxin, microcystin-LR, and locust muscle membrane patches containing
      potassium channels were studied using patch-clamp techniques. A correspondence
      was established between the presence of open channels and pores and the amplitude
      of the 1st harmonic of the total membrane current when the membranes or patches
      were subjected to pressure oscillations. The 2nd harmonic of the membrane current
      provided a measure of the amplitude of a membrane curvature induced by pressure,
      thus making it possible to determine the membrane flexoelectric coefficient. This
      study shows that flexoelectricity could be an effective driving force for ion
      transport through membrane pores and channels, thus further highlighting the
      possible biological significance of this mechano-electric phenomenon.

PMID- 8253056
TI  - Effect of hypoxia and hyperoxia on postpneumonectomy compensatory lung growth.
AB  - To study the effect of chronic hyperoxia and hypoxia on pneumonectomy-induced
      compensatory lung growth, 4-week-old male rats were randomly divided into 4
      groups: pneumonectomy controls, pneumonectomy hyperoxic group (fraction of
      ambient oxygen [FO2] 0.35), pneumonectomy hypoxic group (FO2 0.14), and
      unoperated controls. After 2 weeks, somatic growth of pneumonectomy hypoxic rats
      was diminished. Compared to unoperated controls, lung weight increased in all
      pneumonectomy groups but lung volume increased only in pneumonectomy control and
      pneumonectomy hypoxic rats. Alveolar surface area also increased in pneumonectomy
      control and pneumonectomy hypoxic animals. Lung weight, volume, and alveolar
      surface area in pneumonectomy hypoxic rats were also significantly higher than in
      pneumonectomy hyperoxic rats. When lung weight, volume, alveolar surface area,
      and total number of alveoli were normalized for body weight, the values were
      significantly higher in pneumonectomized hypoxic rats than in the pneumonectomy
      control and pneumonectomy hyperoxic groups. Maximal increase in volume occurred
      in the post-caval and upper lobes in all pneumonectomized groups. Compared to
      unoperated rats, mean linear intercept also increased in the post-caval lobe in
      all pneumonectomized groups. The results suggest that 2 weeks after left
      pneumonectomy, compensatory lung response is incomplete. Chronic hypoxia
      enhances, whereas hyperoxia inhibits compensatory lung growth. The post-caval and
      upper lobes respond more and the lower lobe responds less following left
      pneumonectomy in both hypoxia and hyperoxia.

PMID- 8253057
TI  - Effect of early maternal adrenalectomy on antioxidant enzymes, GSH, ascorbate,
      and uric acid in the rat fetal lung at term.
AB  - Previous studies have shown that the increase of the enzymatic antioxidant
      defense that takes place in the fetal rat lung at the end of gestation can be
      accelerated by the synthetic glucocorticoid dexamethasone and diminished by
      metyrapone, a blocker of glucocorticoid synthesis. Since it is known that the
      fetal adrenal does not start to synthesize corticosterone until the last 20% of
      gestation, pregnant rats were bilaterally adrenalectomized on the first day of
      gestation in order to clarify the role of the endogenous maternal hormone on the
      development of the enzymatic and nonenzymatic antioxidant systems of fetal lung.
      This early adrenalectomy did not change fetal lung catalase, glutathione
      peroxidase, glutathione reductase, cytochrome oxidase, GSH, ascorbate, and uric
      acid at term. The presence of the maternal glands is not essential for lung
      antioxidant development in the fetus and that the stimulus of fetal
      corticosterone during the last 20% of gestation is enough to achieve a normal
      maturation of the fetal lung enzymatic and nonenzymatic antioxidant systems.

PMID- 8253058
TI  - Platelet activating factor stimulates rapid mucin secretion in rat nasal airways
      in vivo.
AB  - Platelet activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine)
      is a potent bronchoconstrictor and has been implicated in the epithelial
      exfoliation, inflammatory cell influx, and mucous hypersecretion associated with
      airways of asthmatics. PAF stimulates mucous secretion in vitro; however, the in
      vivo effects of PAF on airway mucous secretion are not well documented. To assess
      the in vivo effects of PAF on airway mucous-goblet cell secretion, Fischer 344/N
      rats were intranasally instilled with 50 micrograms of PAF or Lyso-PAF (inactive
      precursor and metabolite) in 100 microL of saline or saline alone (50
      microL/naris). Rats were sacrificed 1 or 6 h after instillation, and the anterior
      nasal cavity was processed for light microscopy. Tissue sections were stained
      with either Alcian blue (pH 2.5)/periodic acid-Schiff sequence to detect acidic
      and neutral intraepithelial mucosubstances or Luna's reagent for eosinophilic
      granules to differentiate neutrophils and eosinophils. The numbers of epithelial
      and inflammatory cells and the amounts of intraepithelial mucosubstances within
      the nasal respiratory epithelium were determined by morphometry. Compared to
      saline-instilled controls, intranasal instillation of PAF, but not Lyso-PAF,
      resulted in a significant decrease in the volume density of intraepithelial
      mucosubstances 1 and 6 h after instillation. Intranasal instillation of PAF also
      induced a slight neutrophilic and eosinophilic influx 6 h after instillation and
      a transient decrease in epithelial cell numeric density 1 h post-exposure. Lyso
      PAF had no significant effect on any of the measured parameters. This study
      demonstrates that PAF is a mucous secretagogue in vivo and can induce acute
      airway epithelial responses in rats similar to those seen in the airways of
      asthmatics.

PMID- 8253059
TI  - Massive hemorrhage causes changes in morphometric parameters of lung capillaries
      and concentration of leukocytes in microvasculature.
AB  - The study examines the changes in morphometric lung parameters caused by a
      massive acute blood loss. Three groups of rats were compared: In one group,
      massive hemorrhage was elicited prior to instillation of the fixative; in the
      first reference group, standard instillation fixation was performed, and in the
      second, the circulation was abruptly stopped before instillation of the fixative
      by contracting a snare around the atrioventricular sulcus of the heart. The two
      reference groups showed identical morphometric data except for the capillary
      erythrocyte volume density and its derived parameters, since the standard lung
      fixation procedure leads to a certain hemoconcentration in the lung
      microvasculature, as described previously. In the hemorrhage group the capillary
      volume was reduced to 43% of the value of the snare group. Together with a
      decrease in morphometric hematocrit (from 0.43 to 0.29), this led to a reduction
      of the erythrocyte volume to 27%. The alveolar surface area remained unchanged,
      the capillary surface area showed a tendency to be smaller in the hemorrhage
      group. As a consequence, the morphometric estimate for the pulmonary oxygen
      diffusing capacity DLO2 was reduced to about 40% of the controls. A surprising
      finding was the high leukocyte content in the capillaries after hemorrhage,
      suggesting that the leukocytes are retained in the capillaries even after severe
      blood loss.

PMID- 8253060
TI  - Interleukin-8: an important neutrophil chemotaxin in some cases of exudative
      pleural effusions.
AB  - It was hypothesized that IL-8, a neutrophil chemotaxin, contributes to the influx
      of neutrophils into the pleural cavity of patients with pleural effusions.
      Pleural fluids were collected from 57 patients including 13 with effusions due to
      congestive heart failure, 28 with pleural involvement by carcinoma, 5 with
      empyema, 4 with parapneumonic effusions complicating bacterial pneumonia, 3 with
      hemothorax, 3 with tuberculosis, and 1 with rheumatoid arthritis. All exudate
      groups had significantly higher IL-8 concentrations than the CHF group (p <
      .001). In 18 of the exudate fluids, the concentrations of IL-8 was equal to or in
      excess of the optimal concentration of IL-8 which causes neutrophil chemotaxis in
      vitro. Between 20 and 90% of the chemotactic activity in the fluids was removed
      by absorbing the IL-8 with an IL-8 affinity column. These data showed that IL-8
      is a major chemotaxin in the fluid. The percentage of neutrophils in the fluids
      was not correlated with the IL-8 concentration. Although TNF alpha, a potent
      stimulator of IL-8 production, is present in some pleural effusions, no
      correlation was found between the concentrations of IL-8 and TNF alpha in the
      fluids. The data suggest that IL-8 contributes to the neutrophil influx into the
      pleural space of patients with pleural exudates in conjunction with other
      chemoattractants. It is unlikely that TNF alpha is the sole stimulus for the IL-8
      production in pleural disease states.

PMID- 8253061
TI  - Effect of steroids on the synthesis of complement C3 in a human alveolar
      epithelial cell line.
AB  - The third component of complement, C3, is produced in the lung by several cell
      types, including alveolar epithelial cells. Steroid hormones are important in
      gene regulation in alveolar epithelial cells. The effects of steroids on C3
      production were examined using A549 human pulmonary alveolar epithelial cells.
      Treatment of A549 cells with the glucocorticoids dexamethasone, hydrocortisone,
      corticosterone, and 11-deoxycortisol increased C3 production, as measured by
      ELISA. The glucocorticoid receptor antagonist RU486 inhibited C3 synthesis by
      dexamethasone- and hydrocortisone-stimulated cells. Because the glucocorticoid
      receptor is a member of a superfamily of receptors, the effects of steroid
      members of the superfamily on C3 production were examined. The mineralocorticoid,
      aldosterone, increased C3 production. RU486 completely inhibited aldosterone's
      stimulatory effects on C3 production, whereas the mineralocorticoid receptor
      antagonist spironolactone partially inhibited aldosterone's effects. In contrast,
      testosterone, progesterone 17 alpha-hydroxyprogesterone, and estradiol did not
      alter C3 production by A549 cells. Northern analysis showed that C3 mRNA
      abundance in A549 cells increased following stimulation with dexamethasone,
      hydrocortisone, corticosterone, and aldosterone. Testosterone, progesterone, 17
      alpha-hydroxyprogesterone, and estradiol did not alter C3 mRNA levels. Therefore,
      among the steroids tested, only glucocorticoids and aldosterone altered C3
      production by A549 cells suggesting that these steroids may play a role in the
      regulation of C3 in the lung.

PMID- 8253062
TI  - Crystal structure of an endotoxin-neutralizing protein from the horseshoe crab,
      Limulus anti-LPS factor, at 1.5 A resolution.
AB  - Lipopolysaccharide (LPS), or endotoxin, is the major mediator of septic shock, a
      serious complication of Gram-negative bacterial infections in humans. Molecules
      that bind LPS and neutralize its biological effects or enhance its clearance
      could have important clinical applications. Limulus anti-LPS factor (LALF) binds
      LPS tightly, and, in animal models, reduces mortality when administered before or
      after LPS challenge or bacterial infection. Here we present the high resolution
      structure of a recombinant LALF. It has a single domain consisting of three alpha
      helices packed against a four-stranded beta-sheet. The wedge-shaped molecule has
      a striking charge distribution and amphipathicity that suggest how it can insert
      into membranes. The binding site for LPS probably involves an extended
      amphipathic loop, and we propose that two mammalian LPS-binding proteins will
      have a similar loop. The amphipathic loop structure may be used in the design of
      molecules with therapeutic properties against septic shock.

PMID- 8253063
TI  - Three-dimensional structure of the alkaline protease of Pseudomonas aeruginosa: a
      two-domain protein with a calcium binding parallel beta roll motif.
AB  - The three-dimensional structure of the alkaline protease of Pseudomonas
      aeruginosa, a zinc metalloprotease, has been solved to a resolution of 1.64 A by
      multiple isomorphous replacement and non-crystallographic symmetry averaging
      between different crystal forms. The molecule is elongated with overall
      dimensions of 90 x 35 x 25 A; it has two distinct structural domains. The N
      terminal domain is the proteolytic domain; it has an overall tertiary fold and
      active site zinc ligation similar to that of astacin, a metalloprotease isolated
      from a European freshwater crayfish. The C-terminal domain consists of a 21
      strand beta sandwich. Within this domain is a novel 'parallel beta roll'
      structure in which successive beta strands are wound in a right-handed spiral,
      and in which Ca2+ ions are bound within the turns between strands by a repeated
      GGXGXD sequence motif, a motif that is found in a diverse group of proteins
      secreted by Gram-negative bacteria.

PMID- 8253064
TI  - Tetanus toxin light chain expression in Sertoli cells of transgenic mice causes
      alterations of the actin cytoskeleton and disrupts spermatogenesis.
AB  - Tetanus toxin is a powerful neurotoxin known to inhibit neurotransmitter release.
      The tetanus toxin light chain is a metalloprotease that cleaves some members of
      the synaptobrevin gene family with high specificity. Here, we report the
      expression of a synthetic gene encoding the tetanus toxin light chain in the
      seminiferous epithelium of transgenic mice. Spermatogenesis was severely impaired
      and mature spermatozoa were completely absent. Late spermatids exhibited
      pleomorphic shapes and acrosomal distortions. The number of Leydig cells was
      greatly increased. In situ hybridization analysis revealed that the toxin acts on
      Sertoli cells. Affected cells exhibited an aberrant distribution of actin
      filaments and many cells contained large vacuoles. Our results demonstrate that
      tetanus toxin is active in non-neuronal cells and suggest an important function
      for members of the synaptobrevin gene family during the late stages of
      spermatogenesis.

PMID- 8253065
TI  - Bradyrhizobium japonicum TlpA, a novel membrane-anchored thioredoxin-like protein
      involved in the biogenesis of cytochrome aa3 and development of symbiosis.
AB  - We report the discovery of a bacterial gene, tlpA, that codes for a hitherto
      unknown type of thioredoxin-like protein. The gene was found in the course of
      studying a Tn5 insertion mutant of the soybean root nodule symbiont
      Bradyrhizobium japonicum. The TlpA protein shared up to 31% amino acid sequence
      identity with various eukaryotic and prokaryotic thioredoxins and protein
      disulfide isomerases, and possessed a characteristic active-site sequence, Trp
      Cys-Val-Pro-Cys. In contrast to all members of the thioredoxin family known to
      date, TlpA was shown to be anchored to the cytoplasmic membrane by means of an N
      terminal transmembrane domain, while the active site-containing part of the
      protein faced the periplasm. The tlpA mutant had a pleiotropic phenotype in that
      it was defective in the development of a nitrogen fixing endosymbiosis and
      exhibited a strongly decreased oxidase activity, as compared with the wild-type.
      Holocytochrome aa3 was spectroscopically undetectable in the mutant, whereas the
      apoprotein of subunit one (CoxA) of this oxidase was still synthesized and
      incorporated into the cytoplasmic membrane. Since cytochrome aa3 is not a
      prerequisite for the development of symbiosis, the results suggest that TlpA is
      involved in at least two independent cellular processes, one of which is an
      essential periplasmic step in the maturation of cytochrome aa3.

PMID- 8253066
TI  - Calmodulin is essential for assembling links necessary for exocytotic membrane
      fusion in Paramecium.
AB  - Calmodulin has long been suspected to be involved in calcium-regulated exocytosis
      but its precise site(s) of action has not yet been identified. In Paramecium, a
      genetic approach to the problem is possible as in vivo-selected mutations in the
      calmodulin gene that prevent the activation of some channels have been
      characterized. Three of these calmodulin mutants were examined for exocytotic
      capacity and the mutant cam1 was found to be defective for exocytosis at 35
      degrees C. The loss of exocytotic capacity in cam1 cells can be restored by
      transformation with the wild-type calmodulin gene, demonstrating that its
      exocytotic lesion is indeed due to the mutation in the calmodulin gene. The cam1
      mutant displays abnormal exocytotic sites at the non-permissive temperature: it
      lacks the links ('rosettes' of intramembranous particles in the plasma membrane
      and the fibrous 'connecting material') which normally connect plasma and
      trichocyst membranes. Upon shift of cam1 cells from the permissive to a non
      permissive temperature, performed sites remain functional. These results
      demonstrate that calmodulin is necessary for the assembly of these links at the
      exocytotic site. These results do not, however, exclude the possibility of
      calmodulin also being involved in Ca(2+)-dependent steps of the stimulus
      exocytosis coupling.

PMID- 8253067
TI  - PrlA suppressor mutations cluster in regions corresponding to three distinct
      topological domains.
AB  - The SecY protein of Escherichia coli and its homologues in other organisms, are
      integral components of the cellular protein translocation machinery. Suppressor
      mutations that alter SecY (the prlA alleles) broaden the specificity of this
      machinery and allow secretion of precursor proteins with defective signal
      sequences. Twenty-five prlA alleles have been characterized. These suppressor
      mutations were found to cluster in regions corresponding to three distinct
      topological domains of SecY. Based on the nature and position of the prlA
      mutations, we propose that transmembrane domain 7 of SecY functions in signal
      sequence recognition. Results suggest that this interaction may involve a right
      handed supercoil of alpha-helices. Suppressor mutations that alter this domain
      appear to prevent signal sequence recognition, and this novel mechanism of
      suppression suggests a proofreading function for SecY. We propose that suppressor
      mutations that alter a second domain of SecY, transmembrane helix 10, also affect
      this proof-reading function, but indirectly. Based on the synthetic phenotypes
      exhibited by double mutants, we propose that these mutations strengthen the
      interaction with another component of the translocation machinery, SecE.
      Suppressor mutations were also found to cluster in a region corresponding to an
      amino-terminal periplasmic domain. Possible explanations for this unexpected
      finding are discussed.

PMID- 8253068
TI  - A novel membrane protein involved in protein translocation across the cytoplasmic
      membrane of Escherichia coli.
AB  - A novel factor, which is a membrane component of the protein translocation
      machinery of Escherichia coli, was discovered. This factor was found in the
      trichloracetic acid-soluble fraction of solubilized cytoplasmic membrane. The
      factor was purified to homogeneity by ion exchange column chromatographies and
      found to be a hydrophobic protein with a molecular mass of approximately 12 kDa.
      The factor caused > 20-fold stimulation of the protein translocation when it was
      reconstituted into proteoliposomes together with SecE and SecY. SecE, SecY, SecA
      and ATP were essential for the factor-dependent stimulation of the activity. The
      factor stimulated the translocation of all three precursor proteins examined,
      including authentic proOmpA. Stimulation of the translocation of proOmpF-Lpp, a
      model presecretory protein, was especially remarkable, since no translocation was
      observed unless proteoliposomes were reconstituted with the factor. Partial amino
      acid sequence of the purified factor was determined. An antibody raised against a
      synthetic peptide of this sequence inhibited the protein translocation into
      everted membrane vesicles, indicating that the factor is playing an important
      role in protein translocation into membrane vesicles. The partial amino acid
      sequence was found to coincide with that deduced from the reported DNA sequence
      of the upstream region of the leuU gene. Cloning and sequencing of the upstream
      region revealed the presence of a new open reading frame, which encodes a
      hydrophobic protein of 11.4 kDa. We propose that the factor is a general
      component of the protein translocation machinery of E. coli.

PMID- 8253069
TI  - Properties of Saccharomyces cerevisiae wee1 and its differential regulation of
      p34CDC28 in response to G1 and G2 cyclins.
AB  - Wee1 is a protein kinase that negatively regulates p34cdc2 kinase activity. We
      have identified a Saccharomyces cerevisiae wee1 homolog encoded by the SWE1 gene.
      SWE1 overexpression arrests cells in G2 with short spindles whereas deletion of
      SWE1 did not alter the cell cycle but did eliminate the G2 delay observed in mih1
      mutants. Swe1 immunoprecipitates were capable of tyrosine phosphorylating and
      inactivating p34CDC28 complexed with Clb2, a G2-type cyclin, but not p34CDC28
      complexed with Cln2, a G1-type cyclin, consistent with the inability of Swe1
      overexpression to inhibit the G1/S transition. These results suggest that
      specific cyclin subunits target p34CDC28 for distinct regulatory controls which
      may be important for ensuring proper p34CDC28 function during the cell cycle.

PMID- 8253070
TI  - A new pair of B-type cyclins from Saccharomyces cerevisiae that function early in
      the cell cycle.
AB  - Two new B-type cyclin genes from Saccharomyces cerevisiae, called CLB5 and CLB6,
      are located in a tail to tail arrangement adjacent to the G2/M phase promoting
      cyclins CLB2 and CLB1, respectively. These genomic cyclin arrays are flanked by
      tRNAs and repeated sequences of Ty elements suggesting an intrachromosomal gene
      duplication followed by an interchromosomal gene duplication. Based on their
      deduced protein sequence the CLB5 and CLB6 genes form a new pair of B-type
      cyclins. They are most related to each other and then to the deduced protein
      sequence of their adjacent genes CLB1 and CLB2. Both genes are periodically
      expressed, peaking early in the cell cycle. Loss of function mutants are viable,
      but clb5- mutants exhibit a delay in S phase whereas clb6- mutants show a delay
      in late G1 and/or S phase. The clb5 mutant phenotype is somewhat more pronounced
      in a double null mutant. Both cyclins have the potential to interact with the
      p34CDC28 kinase in vivo.

PMID- 8253071
TI  - Domain mapping of tube, a protein essential for dorsoventral patterning of the
      Drosophila embryo.
AB  - The tube protein plays an essential role in the signal transduction pathway that
      establishes dorsoventral polarity in the Drosophila melanogaster embryo.
      Characterization of each of four tube mutants revealed a substitution or
      insertion in the amino-terminal half of the protein. This portion of the tube
      protein is also evolutionarily conserved, as demonstrated by isolation and
      sequencing of the Drosophila virilis tube gene. Moreover, RNA microinjection
      assays and germline transformation experiments demonstrated that the amino
      terminal domain alone provides substantial levels of gene function: constructs
      encoding only the amino-terminal domain restore dorsoventral polarity to embryos
      lacking any maternal tube function. In the carboxyterminal domain, sequence
      conservation is concentrated in the five octapeptide repeats. Although the repeat
      containing domain by itself provides no rescue of the tube maternal effect
      phenotype, it is necessary for wild-type levels of tube activity. This domain is
      thus likely to play an ancillary role in axis formation.

PMID- 8253072
TI  - Chimeric retinoic acid/thyroid hormone receptors implicate RAR-alpha 1 as
      mediating growth inhibition by retinoic acid.
AB  - Retinoic acid (RA) affects the growth and differentiation of cells in culture,
      usually to decrease the growth rate. In amphibian limb regeneration RA has the
      remarkable ability to affect pattern formation by changing positional identity,
      but its initial action on the limb is to inhibit division of the blastemal
      progenitor cells. Newt limb blastemal cells also show this inhibition in culture.
      In order to investigate the role of different RA receptors (RARs) in the RA
      response, the hormone binding domain of the newt RARs alpha 1 and delta 1 was
      replaced with the corresponding region from the Xenopus thyroid hormone receptor
      alpha (TR-alpha). In COS cells transfected with each of the chimeras,
      transcription was activated after exposure to thyroid hormone (T3). Their profile
      of activity on three different response elements was indicative of RAR
      specificity and not TR specificity. After transfection of cultured newt blastemal
      cells with a DNA particle gun, the chimeras were equally active in stimulating T3
      dependent transcription of two different synthetic reporter genes. Blastemal
      cells were transfected with chimeras or control plasmids along with a marker
      plasmid expressing beta-galactosidase, exposed to RA or T3 and labelled with
      [3H]thymidine followed by autoradiography. The alpha 1 chimera gave T3-dependent
      inhibition of growth, comparable to the effect exerted by RA itself, whereas the
      delta 1 chimera and control plasmids were inactive. The results imply that RAR
      alpha 1 mediates the effects of RA on blastemal cell growth.

PMID- 8253073
TI  - Ash/Grb-2, a SH2/SH3-containing protein, couples to signaling for mitogenesis and
      cytoskeletal reorganization by EGF and PDGF.
AB  - The Src homology (SH) region 2 binds to phosphorylated tyrosine residues and SH3
      domains may interact with cytoskeletal molecules and GTPase-activating proteins
      for Rho/Rac proteins (the small GTP-binding proteins related to Ras). The
      recently cloned Ash/Grb-2 protein, a 25-28 kDa molecule composed entirely of SH2
      and SH3 domains, is a mammalian homolog of the Caenorhabditis elegans Sem-5
      protein, which communicates between a receptor protein tyrosine kinase and a Ras
      protein. In the present study the function of Ash/Grb-2 was investigated by
      microinjecting cells with an anti-Ash antibody. The antibody abolished both S
      phase entry and the reorganization of actin assembly to ruffle formation upon
      stimulation with epidermal growth factor (EGF) and platelet-derived growth factor
      (PDGF). On the other hand, anti-Ash antibody had no effect on S phase entry or
      actin stress fiber formation induced by either serum or lysophosphatidic acid.
      Since the induction of DNA synthesis, ruffle induction and stress fiber formation
      involve a function of Ras, Rac activation and Rho activation respectively, the
      findings strongly suggest that Ash plays a critical role in the signaling of both
      pathways downstream from growth factor receptors to Ras and Rac. Consistent with
      this, Ash co-precipitated with EGF receptor from EGF-stimulated cells. Other
      proteins of approximately 21, 29, 135 and 160 kDa were also detected in the anti
      Ash antibody immunoprecipitates, suggesting a role of Ash as a linker molecule in
      signal transduction downstream of growth factor receptors.

PMID- 8253074
TI  - RapV12 antagonizes Ras-dependent activation of ERK1 and ERK2 by LPA and EGF in
      Rat-1 fibroblasts.
AB  - Rap1 is a small Ras-related GTPase which when over-expressed is able to revert
      transformation by Ki-Ras. We have investigated the role of Rap1 in regulating
      'normal' Ras function by studying the activation of the mitogen-activated protein
      (MAP) kinases ERK1 and ERK2 by two fundamentally different growth factors,
      epidermal growth factor (EGF) and 1-oleoyl-lyso-phosphatidic acid (LPA).
      Conditional expression of RasN17 (a dominant-negative mutant) in Rat-1 cells
      inhibited activation of MAP kinases by EGF and also LPA, the first time a defined
      G-protein-coupled receptor mitogen has been shown to require Ras to exert its
      effects. Conditional or constitutive expression of even low levels of RapV12 (a
      mutant insensitive to Rap-GAP) attenuated activation of MAP kinases by EGF and
      LPA, but did not interfere with growth factor-stimulated increases in Ras-GTP,
      indicating that signalling from receptors to Ras was not impaired. Inhibition of
      Ras-mediated signalling with either RasN17 or RapV12 attenuated DNA synthesis by
      EGF and LPA. We conclude that receptor tyrosine kinases and G-protein-coupled
      receptors use Ras as a common step in signalling to MAP kinases and that Rap-GTP
      (RapV12) at physiological levels interferes with downstream signalling from Ras
      to MAP kinases in vivo.

PMID- 8253075
TI  - Inter-species chimeras of leukaemia inhibitory factor define a major human
      receptor-binding determinant.
AB  - Human leukaemia inhibitory factor (hLIF) binds to both human and mouse LIF
      receptors (LIF-R), while mouse LIF (mLIF) binds only to mouse LIF-R. Moreover,
      hLIF binds with higher affinity to the mLIF-R than does mLIF. In order to define
      the regions of the hLIF molecule responsible for species-specific interaction
      with the hLIF-R and for the unusual high-affinity binding to the mLIF-R, a series
      of 15 mouse/human LIF hybrids has been generated. Perhaps surprisingly, both of
      these properties mapped to the same region of the hLIF molecule. The predominant
      contribution was from residues in the loop linking the third and fourth helices,
      with lesser contributions from residues in the third helix and the loop
      connecting the second and third helices in the predicted three-dimensional
      structure. Since all chimeras retained full biological activity and receptor
      binding activity on mouse cells, and there was little variation in the specific
      biological activity of the purified proteins, it can be concluded that the
      overall secondary and tertiary structures of each chimera were intact. This
      observation also implied that the primary binding sites on mLIF and hLIF for the
      mLIF-R were unaltered by inter-species domain swapping. Consequently, the site on
      the hLIF molecule that confers species-specific binding to the hLIF-R and higher
      affinity binding to the mLIF-R, must constitute an additional interaction site to
      that used by both mLIF and hLIF to bind to the mLIF-R. These studies define a
      maximum of 15 amino acid differences between hLIF and mLIF that are responsible
      for the different properties of these proteins.

PMID- 8253076
TI  - Protein phosphatase activity is required for light-inducible gene expression in
      maize.
AB  - Chlorophyll accumulation and photosynthetic gene activation are two hallmarks of
      greening process in etiolated maize leaves in response to light signals. However,
      very little is known about the relevant signal transduction pathways mediating
      these essential processes that lead to photosynthetic competence. It is shown
      here that a potent and specific protein phosphatase 1 (PP1) and PP2A inhibitor,
      okadaic acid, efficiently blocks chlorophyll accumulation induced by light in
      etiolated maize leaves. In addition, the light-inducible expression of two
      photosynthetic fusion genes can be specifically suppressed by the structurally
      unrelated PP1 and PP2A inhibitors, okadaic acid and calyculin A, using a
      sensitive and physiological maize protoplast transient assay. The specificity and
      effective concentration of the inhibitors in vivo and in vitro strongly suggest
      that PP1 is required for transmitting light signals. Intriguingly, several
      partial cDNAs encoding novel as well as conserved PP1 can be identified in maize
      leaves using the polymerase chain reaction. Studies of chimeric promoters
      indicate that PP1 activity is essential for the interaction of multiple
      regulatory elements. Although PP1 and PP2A have been implicated in the
      suppression of gene activity in yeast and animals, the present data indicate that
      PP1 appears to be essential for light-dependent gene activation in plants.

PMID- 8253077
TI  - The Athb-1 and -2 HD-Zip domains homodimerize forming complexes of different DNA
      binding specificities.
AB  - The Arabidopsis Athb-1 and -2 proteins are characterized by the presence of a
      homeodomain (HD) with a closely linked leucine zipper motif (Zip). We have
      suggested that the HD-Zip motif could, via dimerization of the leucine zippers,
      recognize dyad-symmetric DNA sequences. Here we report an analysis of the DNA
      binding properties of the Athb-1 homeodomain-leucine zipper (HD-Zip-1) domain in
      vitro. DNA binding analysis performed using random-sequence DNA templates showed
      that the HD-Zip-1 domain, but not the Athb-1 HD alone, binds to DNA. The HD-Zip-1
      domain recognizes a 9 bp dyad-symmetric sequence [CAAT(A/T)ATTG], as determined
      by selecting high-affinity binding sites from random-sequence DNA. Gel
      retardation assays demonstrated that the HD-Zip-1 domain binds to DNA as a dimer.
      Moreover, the analysis of the DNA binding activity of Athb-1 derivatives
      indicated that a correct spatial relationship between the HD and the Zip is
      essential for DNA binding. Finally, we determined that the Athb-2 HD-Zip domain
      recognizes a distinct 9 bp dyad-symmetric sequence [CAAT(G/C)ATTG]. A model of
      DNA binding by the HD-Zip proteins is proposed.

PMID- 8253078
TI  - Both Arabidopsis TATA binding protein (TBP) isoforms are functionally identical
      in RNA polymerase II and III transcription in plant cells: evidence for gene
      specific changes in DNA binding specificity of TBP.
AB  - Promoters of pol II and pol III transcribed U-snRNA genes in plants have
      identical sequence elements comprised of a -30 TATA box and an upstream sequence
      element (USE), located four or three helical turns upstream of the TATA box in
      pol II and pol III genes, respectively; it is this difference in element spacing
      that determines the RNA polymerase specificity of the gene. We are interested in
      identifying factors binding to U-snRNA gene promoters and their role in selection
      of RNA polymerase. In this work we have investigated possible differences in the
      activity of the two TATA binding proteins (TBPs) encoded by two different TBP
      genes of Arabidopsis. Using mutant TBPs with altered DNA binding specificity,
      similar to those described previously in yeast, we show that two Arabidopsis TBP
      isoforms are equally active with both pol II and pol III U-snRNA genes and with
      an mRNA gene transfected into plant protoplasts. In contrast to yeast, where
      modified TBP permits transcription only from promoters containing the TGTAAA
      mutant of the consensus (TATAAA) TATA element, altered Arabidopsis TBPs also
      suppress other TATA box mutants. Similar results were obtained with human and
      yeast TBP mutants expressed in plant cells. Interestingly, in several cases
      suppression of different TATA box mutants by altered TBPs was gene or RNA
      polymerase specific suggesting that assembly of TBP into specific complexes
      containing different TBP-associated factors may alter DNA binding specificity of
      the protein.

PMID- 8253079
TI  - A selective defect in IgG2b switching as a result of targeted mutation of the I
      gamma 2b promoter and exon.
AB  - LPS stimulation of B lymphocytes induces germline transcription of and subsequent
      switching to the gamma 2b gene. Mature germline transcripts contain an I exon
      (non-coding) spliced to the C gamma 2b exons. To investigate the role of germline
      transcription and/or transcripts in heavy chain class switching, we have replaced
      the germline I gamma 2b promoter and I exon in ES cells with an expressed
      neomycin resistance gene. The mutated chromosome retains the downstream target
      sequence for switch recombination (S regions) and all sequences necessary for
      expression of a switched gamma 2b gene. Wild-type or mutant ES cells were
      injected into RAG-2 deficient blastocysts to generate somatic chimeras in which
      all lymphocytes were ES-cell derived. Chimeras derived from injection of
      heterozygous mutant ES cells had normal levels of serum IgG2b, but their splenic
      B cells showed a partial decrease in ability to switch to gamma 2b. Strikingly, B
      lymphocytes from chimeras derived by injection of homozygous mutant ES cells were
      deficient in IgG2b production both in vivo and in vitro, but normal with respect
      to production of other Ig heavy chain isotypes. Additional studies demonstrated
      that lack of ability to produce IgG2b by the mutant B cells correlated with lack
      of germline transcription and resulted from a specific defect in class-switch
      recombination to S gamma 2b. Together, these studies demonstrate that the I
      region is an important regulatory element for control of class-switch
      recombination.

PMID- 8253080
TI  - A cooperative interaction between NF-kappa B and Sp1 is required for HIV-1
      enhancer activation.
AB  - The human immunodeficiency virus (HIV-1) long terminal repeat (LTR) contains two
      binding sites for NF-kappa B in close proximity to three binding sites for the
      constitutive transcription factor, Sp1. Previously, stimulation of the HIV
      enhancer in response to mitogens has been attributed to the binding of NF-kappa B
      to the viral enhancer. In this report, we show that the binding of NF-kappa B is
      not by itself sufficient to induce HIV gene expression. Instead, a protein
      protein interaction must occur between NF-kappa B and Sp1 bound to an adjacent
      site. Cooperativity both in DNA binding and in transcriptional activation of NF
      kappa B and Sp1 was confirmed by electrophoretic mobility shift gel analysis,
      DNase footprinting, chemical cross-linking and transfection studies in vivo. With
      a heterologous promoter, we find that the interaction of NF-kappa B with Sp1 is
      dependent on orientation and position, and is not observed with other elements,
      including GATA, CCAAT or octamer. An increase in the spacing between the kappa B
      and Sp1 elements virtually abolishes this functional interaction, which is not
      restored when these sites are brought back into the same helical position.
      Several other promoters regulated by NF-kappa B also contain kappa B in proximity
      to Sp1 binding sites. These findings suggest that an interaction between NF-kappa
      B and Sp1 is required for inducible HIV-1 gene expression and may serve as a
      regulatory mechanism to activate specific viral and cellular genes.

PMID- 8253081
TI  - Adenovirus E1A negatively and positively modulates transcription of AP-1
      dependent genes by dimer-specific regulation of the DNA binding and
      transactivation activities of Jun.
AB  - Adenovirus E1A proteins inhibit expression of the collagenase gene but activate
      expression of the c-jun gene. Both effects are mediated by TPA-responsive
      elements (TREs), the binding sites for members of the AP-1 transcription factor
      family. By a process that is independent of the retinoblastoma gene product, E1A
      distinguishes between different AP-1 factors: in vivo binding of Jun/Jun
      homodimers and Jun/Fos heterodimers to the collagenase TRE is totally blocked by
      E1A while, in contrast, there is no inhibition of Jun/ATF-2 binding to the TRE
      sequences in the c-jun promoter. Altered phosphorylation of the DNA binding
      domain of cJun is not involved in the inhibition of cJun/cJun and cJun/cFos
      binding. E1A does, however, cause hyperphosphorylation of the transactivation
      domain of cJun, which is likely to be responsible for the enhanced c-jun
      transcription by E1A mediated through cJun/ATF-2 heterodimers.

PMID- 8253082
TI  - Common and unique transcription factor requirements of human U1 and U6 snRNA
      genes.
AB  - The human U1 and U6 genes have similar basal promoter structures. A first
      analysis of the factor requirements for the transcription of a human U1 gene by
      RNA polymerase II in vitro has been undertaken, and these requirements compared
      with those of human U6 gene transcription by RNA polymerase III in the same
      extracts. Fractions containing PSE-binding protein (PBP) are shown to be
      essential for transcription of both genes, and further evidence that PBP itself
      is required for U1 as well as U6 transcription is presented. On the other hand,
      the two genes have distinct requirements for TATA-binding protein (TBP). On the
      basis of chromatographic and functional properties, the TBP, or TBP complex,
      required for U1 transcription appears to differ from previously described
      complexes required for RNA polymerase I, II or III transcription. The different
      TBP requirements of the U1 and U6 promoters are reflected by specific association
      with either TFIIB or TFIIIB respectively, thus providing a basis for differential
      RNA polymerase selection.

PMID- 8253083
TI  - Poliovirus RNA synthesis utilizes an RNP complex formed around the 5'-end of
      viral RNA.
AB  - The structure of a ribonucleoprotein complex formed at the 5'-end of poliovirus
      RNA was investigated. This complex involves the first 90 nucleotides of
      poliovirus genome which fold into a cloverleaf-like structure and interact with
      both uncleaved 3CD, the viral protease-polymerase precursor, and a 36 kDa
      ribosome-associated cellular protein. The cellular protein is required for
      complex formation and interacts with unpaired bases in one stem-loop of the
      cloverleaf RNA. Amino acids within the 3C protease which are important for RNA
      binding were identified by site-directed mutagenesis and the crystal structure of
      a related protease was used to model the RNA binding domain within the viral 3CD
      protein. The physiologic importance of the ribonucleic-protein complex is
      suggested by the finding that mutations that disrupt complex formation abolish
      RNA replication but do not affect RNA translation or stability. Based on these
      structural and functional findings we propose a model for the initiation of
      poliovirus RNA synthesis where an initiation complex consisting of 3CD, a
      cellular protein, and the 5'-end of the positive strand RNA catalyzes in trans
      the initiation of synthesis of new positive stranded RNA.

PMID- 8253085
TI  - DbpA: a DEAD box protein specifically activated by 23s rRNA.
AB  - The Escherichia coli protein DbpA is a member of the 'DEAD box' family of
      putative RNA-dependent ATPases and RNA helicases, so called because they share
      the highly conserved motif Asp-Glu-Ala-Asp, together with several other conserved
      elements. We have investigated DbpA expression under conditions where an
      endogenous promoter is used. In this context, translation initiation does not
      occur at the previously identified AUG, but at an upstream, in-frame GUG.
      Mutation of the GUG initiation codon to AUG virtually abolishes DbpA expression,
      suggesting an unusual translation initiation mechanism. Using an inducible
      overexpression plasmid, we have purified milligram quantities of DbpA to
      homogeneity and shown that the purified protein hydrolyses ATP in an RNA
      dependent manner. This ATPase activity is interesting in that, unlike that of
      other DEAD box proteins investigated to date, it absolutely requires a specific
      bacterial RNA, which we have identified as 23S rRNA. This observation is
      particularly significant since DbpA will bind other RNAs and DNA, but will only
      hydrolyse ATP in the presence of 23S rRNA.

PMID- 8253084
TI  - Pathways for selection of 5' splice sites by U1 snRNPs and SF2/ASF.
AB  - We have used protection against ribonuclease H to investigate the mechanisms by
      which U1 small nuclear ribonucleoprotein particles (snRNPs) determine the use of
      two alternative 5' splice sites. The initial binding of U1 snRNPs to alternative
      consensus splice sites was indiscriminate, and on a high proportion of pre-mRNA
      molecules both sites were occupied simultaneously. When the sites were close,
      this inhibited splicing. We propose that double occupancy leads to the use of the
      downstream site for splicing and that this is the cause of the proximity effect
      seen with strong alternative splice sites. This model predicts that splicing to
      an upstream site of any strength requires a low affinity of U1 snRNPs for the
      downstream site. This prediction was tested both by cleaving the 5' end of U1
      snRNA and by altering the sequence of the downstream site of an adenovirus E1A
      gene. The enhancement of downstream 5' splice site use by splicing factor SF2/ASF
      appears to be mediated by an increase in the strength of U1 snRNP binding to all
      sites indiscriminately.

PMID- 8253086
TI  - Initiation codon mutations in the Chlamydomonas chloroplast petD gene result in
      temperature-sensitive photosynthetic growth.
AB  - The chloroplast petD gene encodes subunit IV of the cytochrome b6/f complex and
      is required for photosynthetic electron transport. We have created Chlamydomonas
      strains in which the initiation codon of the petD gene has been changed to AUU or
      AUC. These mutants can grow photosynthetically at room temperature, but not at 35
      degrees C. The accumulation of subunit IV during photosynthetic or heterotrophic
      growth at room temperature is reduced to 10-20% of the wild-type level; petD mRNA
      abundance is reduced to approximately 50% of the wild-type amount. Pulse labeling
      experiments indicate that at room temperature, subunit IV translation proceeds at
      10-20% of the wild-type rate. Cells grown heterotrophically at 35 degrees C
      accumulate < 5% as much subunit IV as wild-type cells grown under the same
      conditions, and < 1% as much subunit IV as wild-type cells grown at room
      temperature. We conclude that translation initiation in these mutants is
      inefficient, leading to decreased translation and accumulation of subunit IV. At
      35 degrees C, translational inefficiency leads directly or indirectly to
      insufficient accumulation of subunit IV to support photosynthetic growth.

PMID- 8253087
TI  - Antitermination of amidase expression in Pseudomonas aeruginosa is controlled by
      a novel cytoplasmic amide-binding protein.
AB  - Amide-inducible expression of the aliphatic amidase system of Pseudomonas
      aeruginosa can be reconstituted in Escherichia coli with only the amidase
      structural gene amiE, the negative regulator amiC and the positive regulator
      amiR, a transcription antitermination factor. Complementation experiments in E.
      coli suggest that negative control of amidase expression by AmiC is mediated by a
      protein-protein interaction with AmiR. Purified AmiC binds acetamide with a KD of
      3.7 microM in equilibrium dialysis studies, and therefore AmiC appears to be the
      sensory partner of the AmiC/AmiR pair of regulatory proteins, responding to the
      presence of amides. Sequence analysis techniques suggest that AmiC is a member of
      the structural family of periplasmic binding proteins, but has a distinct and
      novel cytoplasmic role.

PMID- 8253088
TI  - Measurement of gene expression by translational coupling: effect of copy
      mutations on pT181 initiator synthesis.
AB  - We have prepared and analyzed two types of gene fusion between the replication
      initiator gene, repC, and the reporter gene, blaZ, in order to investigate the
      relationship between pT181 plasmid copy number and RepC initiator protein
      production. A series of pT181 copy mutant plasmids, with copy numbers ranging
      from 70 to 800 copies per cell, were analyzed. In one type of gene fusion used in
      this study, blaZ was translationally coupled to the C-terminal end of the repC
      coding sequence such that native forms of both proteins were produced. This gene
      fusion arrangement, which permitted monitoring of RepC production (as BlaZ
      activity) by plasmids using the protein for their own replication, demonstrated a
      linear relationship, with one exception, between RepC production and plasmid copy
      number over a 20-fold range. In the second type of fusion, blaZ was
      translationally fused to the C-terminal end of repC. As the translational fusion
      did not produce active RepC protein, the fusion-containing pT181 derivatives were
      maintained in a strain which provided RepC in trans, and were thus analyzed at
      constant copy number. In contrast to previous analyses of this type, our
      translational fusion constructs expressed repC at levels proportional to the copy
      numbers of the plasmids from which the fusions were prepared. Using these data,
      we have calculated a minimum figure for the number of RepC molecules synthesized
      per replication event.

PMID- 8253089
TI  - Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb
      fragments prior to or in the absence of internucleosomal fragmentation.
AB  - To date, apoptosis has been characterized biochemically by the production of 180
      200 bp internucleosomal DNA fragments resulting from the activation of an
      endonuclease(s). The principal morphological feature of apoptosis is the
      condensation of chromatin and it has been assumed that this may reflect the
      oligonucleosomal fragmentation pattern. We have re-examined this dogma by
      comparing the biochemical and morphological features of cell death in several
      epithelial cell types (HT-29-I1 colon adenocarcinoma, CC164 mink lung, DU-145
      human prostatic carcinoma and MCF-7 human breast adenocarcinoma) and one
      mesenchymal cell line (H11ras-R3 ras-transformed rat fibroblasts). Cell death was
      induced either by serum deprivation, TGF-beta 1 or etoposide, or by leaving cells
      to reach confluence. Cell death was assessed with respect to detachment from
      monolayers, morphological changes and DNA integrity. The DNA-binding fluorophore
      Hoechst 33258 revealed chromatin condensation patterns consistent with apoptotic
      cell death in all cell types except MCF-7 cells. Using field inversion gel
      electrophoresis in conjunction with conventional 2% agarose gel electrophoresis,
      cleavage of DNA to 50 kbp fragments was observed in all cases except MCF-7 cells.
      This preceded the appearance of oligonucleosomal fragments in HT-29-I1, CC164 and
      H11ras-R3 cells. Although the DNA of DU-145 cells fragmented into 50 kbp units,
      and although the cells exhibited classical apoptotic morphology, no subsequent
      internucleosomal cleavage was observed. These results suggest that changes in the
      integrity of DNA indicative of the release of chromatin loop domains occur before
      cleavage at internucleosomal sites is initiated and that the latter is not an
      essential step in the apoptotic process.

PMID- 8253090
TI  - Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair
      defects in vitro.
AB  - The mammalian ERCC1-encoded polypeptide is required for nucleotide excision
      repair of damaged DNA and is homologous to Saccharomyces cerevisiae RAD10, which
      functions in repair and mitotic intrachromosomal recombination. Rodent cells
      representing repair complementation group 1 have nonfunctional ERCC1. We report
      that repair of UV-irradiated DNA can be reconstituted by combining rodent group 1
      cell extracts with correcting protein from HeLa cells. Background repair was
      minimized by employing fractionated rodent cell extracts supplemented with human
      replication proteins RPA and PCNA. Group 1-correcting activity has a native
      molecular mass of 100 kDa and contains the 33 kDa ERCC1 polypeptide, as well as
      complementing activities for extracts from rodent group 4 and xeroderma
      pigmentosum group F (XP-F) cells. Extracts of group 1, group 4 or XP-F cells do
      not complement one another in vitro, although they complement extracts from other
      groups. The amount of ERCC1 detectable by immunoblotting is reduced in group 1,
      group 4 and XP-F extracts. Recombinant ERCC1 from Escherichia coli only weakly
      corrected the group 1 defect. The data suggest that ERCC1 is part of a functional
      protein complex with group 4 and XP-F correcting activities. The latter two may
      be equivalent to one another and analogous to S. cerevisiae RAD1.

PMID- 8253091
TI  - Evidence for a repair enzyme complex involving ERCC1 and complementing activities
      of ERCC4, ERCC11 and xeroderma pigmentosum group F.
AB  - Nucleotide excision repair (NER), one of the major cellular DNA repair systems,
      removes a wide range of lesions in a multi-enzyme reaction. In man, a NER defect
      due to a mutation in one of at least 11 distinct genes, can give rise to the
      inherited repair disorders xeroderma pigmentosum (XP), Cockayne's syndrome or
      PIBIDS, a photosensitive form of the brittle hair disease trichothiodystrophy.
      Laboratory-induced NER-deficient mutants of cultured rodent cells have been
      classified into 11 complementation groups (CGs). Some of these have been shown to
      correspond with human disorders. In cell-free extracts prepared from rodent CGs 1
      5 and 11, but not in a mutant from CG6, we find an impaired repair of damage
      induced in plasmids by UV light and N-acetoxy-acetylaminofluorene.
      Complementation analysis in vitro of rodent CGs is accomplished by pairwise
      mixing of mutant extracts. The results show that mutants from groups 2, 3, 5 and
      XP-A can complement all other CGs tested. However, selective non-complementation
      in vitro was observed in mutual mixtures of groups 1, 4, 11 and XP-F, suggesting
      that the complementing activities involved somehow affect each other. Depletion
      of wild-type human extracts from ERCC1 protein using specific anti-ERCC1
      antibodies concomitantly removed the correcting activities for groups 4, 11 and
      XP-F, but not those for the other CGs. Furthermore, we find that 33 kDa ERCC1
      protein sediments as a high mol. wt species of approximately 120 kDa in a native
      glycerol gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253092
TI  - Phage P4 alpha protein is multifunctional with origin recognition, helicase and
      primase activities.
AB  - alpha Protein of satellite phage P4 of Escherichia coli is multifunctional in P4
      replication with three activities. First, the protein (subunit M(r) = 84,900)
      complexes specifically the P4 origin and the cis replication region required for
      replication. alpha Protein interacts with all six type I repeats (TGTTCACC)
      present in the origin. Second, associated with the alpha protein is a DNA
      helicase activity that is fueled by hydrolysis of a nucleoside 5' triphosphate.
      All common NTPs except UTP and dTTP can serve as cofactors. Strand separation of
      partial duplexes containing tailed ends that resemble a replication fork is
      preferred, although a preformed fork is not absolutely required for the enzyme to
      invade and unwind duplex DNA. alpha Protein catalyzes unwinding in the 3'-5'
      direction with respect to the strand it has bound. Finally, the primase activity
      already demonstrated for alpha protein is due to synthesis of RNA primers. In
      vitro, alpha protein generates di- to pentaribonucleotides on single-stranded
      phage fd DNA. The predominant product is the dimer pppApG, on which most of the
      longer oligoribonucleotides are based. Using DNA oligonucleotides of defined
      sequence as templates, synthesis of pppApG was also detectable. To date, among
      prokaryotic and eukaryotic replication systems, gp alpha is the only protein
      known that combines three activities on one single polypeptide chain.

PMID- 8253093
TI  - Breast cancer control programme in developing countries.
AB  - Breast cancer is a very important health problem in developing countries, where
      its incidence has increased in the last decades. Mortality rates due to breast
      cancer have also increased, and the main reason for this is late diagnosis. The
      authors demonstrate that organizing programmes for early breast cancer detection
      is possible by making use of simple resources. A set of tiered interventions is
      proposed, stratified in levels of complexity: Level 1--Identification of abnormal
      breast by health professionals; Level 2--Medical assistance to women whose breast
      is considered abnormal, in order to diagnose and treat benign diseases and
      recognize suspect cases of cancer; Level 3--Management of the women with
      suspected or diagnosed breast cancer by a multidisciplinary team. Therefore, a
      proposal for wide action for breast cancer control in developing countries is
      presented.

PMID- 8253094
TI  - Evaluation of the gynaecological oncology situation in the European Community
      countries.
AB  - At the end of 1991 an enquiry was sent to 40 doctors recognized as experts in
      Gynaecological Oncology in the E.C. countries to establish the situation of this
      sub or superspecialty and 32 (80%) answers were received. Inside the E.C.
      countries only the United Kingdom recognized the subspecialty of Gynaecological
      Oncology. Concerning the other 11 countries, except Denmark, their experts
      (invited to answer the questionnaire) consider it is necessary to individualize
      Gynaecological Oncology as a sub or a superspecialty. Before a training period of
      24 or 36 months in Gynaecological Oncology, it is necessary to have the specialty
      of Obstetrics/Gynaecology. The training period must include 50% or 60% in
      diagnosis and surgical treatment, 10% in radiotherapy (only theoretical), 10% or
      20% in medical oncology (theoretical and practical), 5% or 10% in oncological
      pathology, basic sciences and general aspects of cancer. Breast diseases,
      including breast cancer, must be a part of the training in Gynaecological
      Oncology and at the end of this period an evaluation test must be made. Lastly,
      the health authorities, of each country, are the best able to recognize the
      individualization of Gynaecological Oncology.

PMID- 8253095
TI  - Uterine fibrinolytic enzymes in endometrial cancer.
AB  - Urokinase (u-PA) induced proteolysis of the extracellular matrix appears to be
      involved in stromal invasion by tumor cells and metastasis. Many malignant cells
      are known to secrete u-PA. Plasminogen activator inhibitor-type 2 (PAI-2) is an
      inhibitor of u-PA and is present in several neoplastic cell lines and malignant
      ascites. We measured u-PA and PAI-2 antigen in tissue homogenates of normal and
      malignant endometrium from 21 postmenopausal patients. Enzyme linked immunoassays
      which measure the bound and unbound, single and two chain form of the activators
      and bound and unbound form of the inhibitor were used. Urokinase was present in
      four of seven normal (range 0.15-0.5, median 0.15 ng/mg protein) and in all
      malignant endometrial homogenates (range 0.41-9.2, median 3.4 ng/mg protein), p <
      0.001. PAI-2 was detectable in four of seven normal endometrial homogenates at
      low concentrations (range 1.1-3.1, median 1.1 ng/mg protein) and in all malignant
      tissue homogenates at higher levels (range 1.6-27.3, median 4.9 ng/mg protein), p
      < 0.01. Levels of PAI-2 were higher in Stage II/III compared to Stage I
      malignancy (p < 0.01) and in cancers that had invaded 50% or more of the uterine
      wall compared to less invasive cancers, p < 0.01. PAI-2 may be useful as a
      prognostic marker in endometrial cancer.

PMID- 8253096
TI  - The clinical, serological, pathological and immunocytochemical features of a case
      of primary carcinoma of the fallopian tube.
AB  - We report the case of a patient with Stage I fallopian tube carcinoma who
      underwent bilateral salpingo-oophorectomy, total hysterectomy, omentectomy and
      appendicectomy followed by cisplatin based chemotherapy. CA 125 antigen was
      immunocytochemically detected in more than 50% of neoplastic cells, and serum CA
      125 assay correlated with the clinical course of disease. Since CA 125 levels
      progressively increased during chemotherapy, an immunoscintigraphy with 111 In
      labeled CA 125 monoclonal antibody was performed and revealed a 5 cm area of
      abnormal captation placed in the posterior abdominal wall next the left kidney. A
      CAT scan detected an enlargement of left para-aortic lymph nodes, without
      cleavage plane with the left psoas muscle. The present case confirms that serum
      CA 125 assay is a useful noninvasive tool in the management of fallopian tube
      carcinoma.

PMID- 8253097
TI  - Prognostic impact of peritoneal cytology in patients with endometrial carcinoma.
AB  - In 169 patients with all stages of endometrial cancer peritoneal cytology was
      performed and the finding correlated to the stage of disease, histologic grade,
      depth of myometrial invasion, tumor site in the uterine cavity, menstrual status,
      frequency of recurrence and 5-year survival. In 23 (11.6%) patients malignant
      cells were found in the peritoneal washing. In patients with Stage I endometrial
      cancer 6.5%, Stage II 9.1%, and in those in whom disease had spread outside the
      uterus (Stage III and IV) in 68.0% (p < 0.001). Positive peritoneal cytology was
      found significantly more frequently in patients with maintained menstrual cycle
      (p < 0.01), patients with tumor localized in uterine horns and in those patients
      with low values of steroid receptors. With regard to the histologic grade no
      difference was found in peritoneal cytology regardless of the stage of the
      disease. With regard to the myometrial invasion difference in the finding of
      malignant cells was found only in those patients in whom the tumor had spread
      outside the uterus (p < 0.05). Regardless of the stage of the disease, the
      frequency of recurrence and 5-year survival did not correlate with the finding of
      malignant cells in peritoneal lavage. According to our results the finding of
      peritoneal cytology, as an isolated prognostic factor, or in correlation with
      other prognostic factors, does not play an important role in the prognosis of
      patients with endometrial cancer, particularly those in whom the tumor is
      localized only in the uterus.

PMID- 8253098
TI  - Prognosis factors in cancer of the vulva.
AB  - A series of factors and its possible influence on the prognosis of cancer of the
      vulva are analyzed. In the present study 71 patients were studied. We have been
      able to establish that the main prognosis factor of cancer of the vulva is,
      beyond doubt, the presence of lymph node metastasis, since in absence of lymph
      node affection due to the cancer, survival was 100%, after five years, in those
      patients having positive lymph nodes, survival was 92.5% after the first year,
      82.5% after three years and 70% after five years.

PMID- 8253099
TI  - Surgical treatment of vulvar cancer.
AB  - Two hundred and seventy two women with vulvar cancer were submitted to standard
      surgical treatment. In 127 women (46.7%) regional lymph nodes were involved. Out
      of 181 women (66.5%) who survived 5 years, 132/145 women (91%) were with negative
      nodes and 49/127 women (38.6%) were with positive nodes. Surgical management of
      vulvar cancer is discussed, especially inguinal lymphadenectomy.

PMID- 8253100
TI  - Abnormal cervical PAP smear leading to the diagnosis of gastrointestinal cancer
      without cervico-vaginal metastases.
AB  - We report the case of an unsuspected G.I. cancer in a patient with no clinical
      signs other than ascites and positive PAP-smear on admission. Histologically,
      neither endometrium nor cervix were involved. To date, only 2 cases of primary
      gastrointestinal (gastric) cancers with no metastases to the cervix, suspected by
      PAP-smear, have been reported in medical literature. A few more have been
      reported with cervical metastases. The suspicion of intraabdominal adenocarcinoma
      was based on the evidence of signet ring cells found in the smear with negative
      cervical biopsies and negative fractional curettage. A postmortem examination
      confirmed the absence of genital involvement. Our aim is to remind the clinician
      that an abnormal PAP-smear, due to non gynecological malignancies, can, on rare
      occasions, be observed. In order to obtain a positive cervico-vaginal PAP-smear
      by a non gynecologic intraabdominal exfoliating cancer, both previous literature
      and our case suggest peritoneal effusion to be of major importance.

PMID- 8253101
TI  - Primary malignant lymphoma of the uterine cervix. A clinicopathological
      evaluation of 3 cases.
AB  - Three cases of primary malignant lymphoma of the uterine cervix are presented; 1
      in pre- and 2 in postmenopausal women. Two presented clinically with bleeding,
      one with pelvic discomfort. Histologically all were B cell lymphomas, two high,
      one low malignancy. Radiotherapy to the whole pelvis followed hysterectomy in 2
      patients and in one wasthe primory modality. One of the patients was also treated
      with chemotherapy for dissemination within the abdomen and CNS. Two patients
      died, one is well at 38 months.

PMID- 8253102
TI  - Leiomyosarcoma of the vulva.
AB  - A case of Leiomyosarcoma of the vulva is presented. It is important to discuss
      diagnosis and treatment because of its rarity and usual presentation as a benign
      lesion. Radical vulvectomy with bilateral groin dissection was performed. Local
      recurrence occurred four years after surgery and was re-excised. At present, the
      patient is alive with no evidence of disease.

PMID- 8253103
TI  - Human papillomavirus 16 in the blood of women treated for cervical cancer.
AB  - In the present paper we study the behaviors of HPV 16 DNA in the blood of women
      during oncological treatment. Disappearance of HPV from the blood depends on the
      clinical Stage of cancer. It is possible that HPV remaining in the blood for a
      long time after oncological treatment might be some marker showing that the
      cancer tissue was not completely removed. There is some suggestion that detecting
      HPV in the cervix or in the blood of women without morphological lesions but with
      CIN in the past might indicate higher risk of cervical cancer recurrence.

PMID- 8253104
TI  - Value of the CD25+ CD16+ cell determination in defining the prognosis of operable
      breast cancer patients.
AB  - The immunologic status of 40 breast cancer patients with operable disease and 50
      healthy women was studied at the Division of Medical Oncology of the 2nd Medical
      School in Naples. Skin tests and lymphocyte subpopulation determination were
      performed. The same tests were repeated after surgery in the cancer patients. At
      the same time, the immunologic modifications during chemotherapy (CMF) were
      studied in a further 25 premenopausal breast cancer patients. The cancer patients
      did not show significantly different reactivity to recall antigens, nor did
      surgery or chemotherapy modify this parameter. The breast cancer patients showed
      a significantly higher CD4+/CD8+ ratio (2.07 +/- 1.06 vs. 1.56 +/- 0.58; p <
      0.05) and a higher percentage of CD16+ cells (15.7 +/- 7 vs. 9.1 +/- 6; p <
      0.001), than controls. Patients without axillary lymph node involvement showed
      higher CD4+/CD8+ ratio, CD16+ and CD25+ percentage than the N+ patients. The
      percentage of CD25+ cells (expressing functional IL-2 receptor) and CD16+ cells
      proved to be predictive of early relapse: in 14 patients who had relapsed at a 37
      month median follow-up, mean CD25+ and CD16+ cell values at diagnosis were
      significantly lower than those in the remaining 26 (CD25+: 0.87 +/- 0.7 vs. 2.44
      +/- 2.19, p < 0.01; CD16+: 9.4 +/- 6 vs. 17.3 +/- 5, p < 0.001). These data
      suggest that a functional activation may occur in operable breast cancer patients
      except those with axillary node metastatization (especially when more than 3
      axillary lymph nodes are involved).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253105
TI  - Analysis of the cancer cases in the Republic of Panama 1982-1989.

PMID- 8253106
TI  - Hysteroscopy for diagnosis and treatment of endometrial adenocarcinoma
      precursors. A review of literature.
AB  - The guidelines for early detection of adenocarcinoma and its precursors are
      controversial. Ultrasound, due to its non invasive nature, could represent a
      useful technique for screening patients at risk but its specificity is low.
      Endometrial cytology, especially by using new device, is an effective, easy, and
      inexpensive method for screening asymptomatic women; however, cytologic
      investigation shows some limits due to the scarce desquamation of endometrial
      cells and to the difficulty in diagnosing hyperplasia. Blind biopsy can miss the
      pathology in cases of focal lesions. Dilatation and curettage gives, in most
      cases, a certain histologic diagnosis but, requiring anesthesia and
      hospitalization, is not suitable for mass screening; moreover, in cases of focal
      lesions its sensitivity is low. Microhysteroscopy allows an atraumatic and direct
      investigation of the uterine cavity and could be used as a routine basis in
      patients with risk factors for endometrial pathology and signs of
      hyperestrogenism. In symptomatic patients its employment must be considered
      necessary for a correct and modern management of these patients. Operative
      hysteroscopy represents a promising way for treating hyperplastic endometrial
      lesions without signs of atypia, but its value in comparison with hysterectomy
      must be confirmed; when atypia is found, hysterectomy is the treatment of choice.

PMID- 8253107
TI  - Actions of amiodarone on mitochondrial ATPase and lactate dehydrogenase
      activities in guinea pig heart preparations.
AB  - The effects of amiodarone on mitochondrial ATPase (EC 3.6.1.3) and lactate
      dehydrogenase (LDH: EC 1.1.1.27) activities were studied in guinea pig
      mitochondrial preparations in order to test the hypothesis that amiodarone exerts
      some of its effects as a result of multiple actions on membrane-bound enzymes and
      receptors. Amiodarone inhibited the ATPase activity in the range of 10 pM to 10
      mM (n = 10) with IC50 values of 56.4 +/- 7.2 microM. However, although the
      inhibitory action was very significant (P < 0.0001, compared to the control) in
      the concentration range of 100 pM to 10 microM, the differences in individual
      enzyme responses showed very weak correlation with drug concentration. In this
      region, the inhibitory effects were almost constant at approximately 37%. Below
      100 pM and above this range however, the concentration-response relationships
      were steep, reaching total inhibition at approximately 2.5 mM. Amiodarone also
      exerted concentration-dependent inhibitory effects on lactate dehydrogenase
      activity. However, over the effective inhibitory concentration range (5-95%) of
      7.5 microM to 2.5 mM (n = 8) and IC50 value of 108 +/- 6 microM, its inhibitory
      potency was twofold weaker than that of its ATPase inhibition. We propose that
      these actions contribute, at least in part, to the mechanism(s) of some of the
      pharmacological actions of amiodarone.

PMID- 8253108
TI  - Nifedipine inhibits responses to alpha-adrenoceptor stimulation in canine blood
      vessels: impact of heart failure.
AB  - The effects of nifedipine (10(-8) and 10(-7) M) on alpha-adrenergic responses of
      the dorsal pedal artery and saphenous vein were examined from dogs with pacing
      induced heart failure. Two groups of dogs had their right ventricles paced at 250
      beats/min: group (1) 1 week of pacing (mild heart failure) and group (2) paced
      for a mean period of 25.8 days (peak heart failure). Nifedipine non-competitively
      antagonised 6-allyl-2-amino-5,6,7,8-tetrahydro-4H- thiazolo[4,5-d]azepin
      dihydrochloride (BHT 920)-induced contractions to the same extent (i.e. at
      control, mild heart failure and peak heart failure) and IC50 values were as
      follows: for dorsal pedal artery 3.9 (1.8-6.1) nM, 4.4 (1.2-8.4) nM and 8.5 (2.9
      38.9) nM, respectively; for saphenous vein 13.0 (4.6-26.0) nM, 13.0 (7.3-18.6) nM
      and 19.0 (9.3-32.8) nM, respectively). Before the onset of pacing, nifedipine did
      not affect concentration-effect curves generated to noradrenaline or
      phenylephrine in either the artery or the vein. After 1 week of pacing,
      nifedipine (10(-7) M) inhibited contractions to noradrenaline in the artery and
      the vein (70 +/- 5% for the artery and 51 +/- 4% for the vein). Nifedipine had no
      effect on phenylephrine-induced contractions. At peak heart failure, nifedipine
      inhibited both noradrenaline and phenylephrine contractions. These results
      indicate that nifedipine is useful in differentiating contractile activity of
      vascular smooth muscle with respect to alpha-adrenoceptor agonism.

PMID- 8253109
TI  - Comparison of the effects of various vasodilators on the rat portal vein and
      mesenteric artery.
AB  - The effects of various vasodilators on isolated helical strips of rat portal vein
      and mesenteric artery were examined. Dilazep, ibudilast, nifedipine, verapamil
      and papaverine relaxed the KCl- and norepinephrine-induced contractions of the
      portal vein to a greater extent than they relaxed those of mesenteric artery.
      Dibutyryl cyclic AMP and NKH477 did not show any significant difference in terms
      of the concentrations that produced 50% inhibition (IC50) of the KCl-induced
      contraction of the portal vein and mesenteric artery. The relaxant effects of
      nitroprusside and isosorbide dinitrate on the KCl- and norepinephrine-induced
      contractions of the portal vein were less potent than their effects on
      contractions of the mesenteric artery. The agents that inhibited the contractions
      of the portal vein more potently than those of the mesenteric artery were
      associated with parallel shifts to the right of the concentration-response curves
      for CaCl2 in both preparations. These results suggest that drugs with a Ca2+
      channel blocking action may be preferable to those that cause a decrease in
      portal pressure for treatment of portal hypertension.

PMID- 8253110
TI  - Reduced levels of 5-HT3 receptor recognition sites in the putamen of patients
      with Huntington's disease.
AB  - The present study assessed 5-HT3 receptor recognition site levels in homogenates
      of putamen derived from patients with clinically and neurochemically diagnosed
      Huntington's disease or Parkinson's disease and those from age-, sex- and post
      mortem delay-matched neurologically and psychiatrically normal patients to
      investigate the cellular location of 5-HT3 receptors in the human putamen.
      Specific [3H]granisetron (0.91 nM) binding (defined by ondansetron, 10 microM)
      was significantly reduced in putamen homogenates from eight out of ten patients
      with Huntington's disease compared to similar homogenates from 'control' patients
      (72 +/- 6 and 39 +/- 8 fmol/g wet weight, mean +/- S.E.M., n = 10 and 8, tissue
      from 'control' and Huntington's disease patients, respectively, P = 0.004). In
      contrast, specific [3H]granisetron (1.04 nM) binding levels were similar in
      putamen homogenates from patients with Parkinson's disease when compared to
      homogenates from 'control' patients. The present results indicate that at least a
      proportion of the 5-HT3 receptor population in the human putamen is located on
      neurones that have their cell bodies within this brain region and that these
      receptors are not primarily located on dopamine neurone terminals in the human
      putamen.

PMID- 8253111
TI  - Enkephalin antinociception in mice is mediated by delta 1- and delta 2-opioid
      receptors in the brain and spinal cord, respectively.
AB  - Pharmacological evidence for the existence of delta-opioid receptor subtypes has
      been reported. This study was conducted to determine which type of delta-opioid
      receptors was involved supraspinally and spinally when antinociception was
      induced by the natural enkephalins, [Leu5]enkephalin and [Met5]enkephalin. In the
      mouse tail flick assay, the antinociceptive ED50 values of both
      intracerebroventricularly (i.c.v.) administered [Leu5]enkephalin and
      [Met5]enkephalin (together with the peptidase inhibitors, bestatin and thiorphan)
      were significantly increased by 7-benzylidenenaltrexone (BNTX), a selective delta
      1-opioid receptor antagonist but not by naltriben, a selective delta 2-opioid
      receptor antagonist. On the other hand, when the enkephalins were administered
      intrathecally (i.t.), the antinociceptive ED50 values of both enkephalins were
      significantly raised by naltriben but not by BNTX. beta-Endorphin-induced
      (i.c.v.) antinociception was antagonized by naltriben administered i.t. or s.c.
      but not by BNTX administered i.t. or s.c. Different delta-opioid receptor
      subtypes appeared to be involved in supraspinal (delta 1) and spinal (delta 2)
      antinociception induced by endogenous delta-opioid receptor agonists, [Leu5] and
      [Met5]enkephalin. The antinociception produced by i.c.v. administered beta
      endorphin has been attributed to the release of [Met5]enkephalin in the spinal
      cord and its antagonism by naltriben support the finding that enkephalins
      interact with delta 2-opioid receptors in the spinal cord to mediate
      antinociception. beta-Endorphin may be interacting at receptors other than delta
      1- or delta 2-opioid receptors in the brain, perhaps the putative epsilon
      receptors, to mediate their effects because neither i.c.v. administered BNTX nor
      naltriben inhibited its activity.

PMID- 8253112
TI  - The dopamine D3 receptor and autoreceptor preferring antagonists (+)-AJ76 and (+)
      UH232; a microdialysis study.
AB  - The in vivo neurochemical profiles of haloperidol, raclopride and the dopamine D3
      and autoreceptor preferring dopamine receptor antagonists (+)-UH232 and (+)-AJ76
      on dopamine release and metabolism in the dorsal striatum and in the nucleus
      accumbens are described. It is shown that both (+)-UH232 and especially (+)-AJ76
      have different effects on brain dialysate dopamine and 3,4-dihydroxyphenylacetic
      acid (DOPAC) as compared to haloperidol or raclopride. It is suggested that the
      relative increase in dialysate dopamine over the relative increase in DOPAC is a
      neurochemical fingerprint, unique for different dopamine receptor antagonists. As
      a consequence the increased release and metabolism of dopamine after systemic
      administration of dopamine receptor antagonists may be controlled by different
      receptors and different dopamine antagonists can partly distinguish between these
      receptors. This may be due to their different interactions with different
      dopamine D2 type receptors. It is finally concluded that (+)-UH232 and especially
      (+)-AJ76 seem to prefer release regulating autoreceptors at the level of the axon
      terminals.

PMID- 8253113
TI  - Evidence for a role of tachykinin NK2 receptors in mediating brief nociceptive
      inputs to rat dorsal horn (laminae III-V) neurons.
AB  - Since the NK2 receptor-selective tachykinin, neurokinin A is present in fine
      primary afferent neurons in addition to the NK1 receptor-selective tachykinin,
      substance P, we have addressed the relative role of NK1 and NK2 receptors in
      somatosensory processing in spinal dorsal horn. Recording extracellularly from
      rat laminae III-V neurons whilst ionophoresing drugs nearby, the selective NK1
      receptor antagonists L 688,169, GR 82334 and [D-Pro4,D-Trp7,910Phe11]substance P
      (4-11) failed to influence neuronal responses to cutaneous pinch or noxious heat
      but often enhanced responses to innocuous brush. In contrast, the highly
      selective NK2 receptor antagonist L 659,874 profoundly inhibited responses to
      noxious heat but not pinch or brush. Highly selective synthetic agonists for both
      NK1 and NK2 receptors ([N-acetyl-Arg6,Sar9,Met(O2)11]substance P-(6-11) and GR
      64349, respectively) and also NKA showed the inverse effects on sensory responses
      to those brought about by their antagonists. At higher ionophoretic currents,
      both NK1 and NK2 receptor agonists increased spontaneous activity. This increased
      basal firing induced by GR 64349 and neurokinin A (but not that due to [N-acetyl
      Arg6,Sar9,Met(O2)11]substance P-(6-11) appeared to partially pre-empt further
      excitatory responses to noxious heat. It is concluded that although both NK1 and
      NK2 receptors can clearly mediate excitation of dorsal horn neurons, it is not
      NK1, but rather NK2 receptors that are important as the physiological transducer
      of brief thermal nociceptive inputs in this model.

PMID- 8253114
TI  - In vivo imaging of the 5-hydroxytryptamine reuptake site in primate brain using
      single photon emission computed tomography and [123I]5-iodo-6-nitroquipazine.
AB  - Previous experiments have demonstrated that 5-iodo-6-nitro-2-piperazinylquinoline
      (5-I-6-NQP) is a potent and selective ligand for studying brain 5
      hydroxytryptamine (5-HT) reuptake sites. We performed in vivo imaging in non
      human primates using single photon emission computed tomography (SPECT) and the
      123I-labeled compound [123I]5-I-6-NQP. These studies showed rapid brain uptake,
      with slow egress of the tracer from the brainstem, a region rich in 5-HT reuptake
      sites. Loss of the tracer from regions with a lower density of these sites, such
      as cerebellum, was relatively more rapid. Pretreatment of animals with paroxetine
      increased the washout of tracer from the brainstem to rates similar to that seen
      in cerebellum. Brainstem to cerebellar ratios of tracer accumulation were > 2 by
      8 h after injection, and in paroxetine pretreated animals remained close to 1.
      These results indicate that the radiotracer has characteristics suitable for use
      as a SPECT imaging agent of serotonin reuptake sites.

PMID- 8253115
TI  - Serotonin-5-O-carboxymethyl-glycyl[125I]tyrosinamide labels the 5-HT1D beta
      receptor subtype in human cortex.
AB  - This study, carried out in human cerebral cortical membranes, confirms previous
      findings in human substantia nigra that serotonin-5-O-carboxymethyl
      glycyl[125I]tyrosinamide ([125I]GTI) labels a homogeneous population of
      recognition sites consistent with a 5-HT1D receptor pharmacology. In addition the
      results indicate that, under the assay conditions described, [125I]GTI
      specifically labels the 5-HT1D beta recognition site since ketanserin and
      ritanserin display a low affinity consistent with their activities at this
      subtype of the 5-HT1D receptor.

PMID- 8253116
TI  - Adenosine inhibits the release of atrial natriuretic peptide from the perfused
      rat heart.
AB  - The effect of adenosine on atrial natriuretic peptide (ANP) release was studied
      in the perfused rat heart model. Adenosine had no effect on the heart rate of the
      spontaneously beating heart at a concentration of 1 microM, whereas at
      concentrations of 10 and 100 microM it dose-dependently decreased the frequency
      by 17 and 55% (P < 0.05 and P < 0.001, respectively). In the spontaneously
      beating hearts, immunoreactive ANP release was inhibited by adenosine at
      concentrations of 10 and 100 microM (P < 0.05 and P < 0.01). When heart rate was
      maintained constant by external pacing, inhibition of ANP release was observed
      only with 100 microM adenosine (P < 0.01). The results show that adenosine dose
      dependently inhibits ANP release from the perfused rat heart. The effect of
      adenosine on ANP release was partially due to its negative chronotropic effect
      but the results suggest that adenosine may also have a direct inhibitory effect
      on ANP release in atrial myocardium.

PMID- 8253117
TI  - SCH 23390 decreases self-stimulation of the medial prefrontal cortex in the rat.
AB  - We studied the effects of peripheral and central administration of SCH 23390, a
      selective antagonist of dopamine D1 receptors, on intracranial self-stimulation
      of the medial prefrontal cortex of the rat. Intraperitoneal injections of SCH
      23390 produced a dose-related decrease in self-stimulation. Unilateral
      microinjections of SCH 23390 into the medial prefrontal cortex also produced a
      dose-related decrease in self-stimulation in the ipsilateral medial prefrontal
      cortex. However, self-stimulation of the contralateral, noninjected prefrontal
      cortex, used as control, was not affected. Together with previous data, the
      present results suggest that the dopamine neurotransmission involved in self
      stimulation of the prefrontal cortex of the rat is mediated by dopamine D1
      receptors.

PMID- 8253118
TI  - Effects of rimcazole, a specific antagonist of sigma sites, on the antitussive
      effects of non-narcotic antitussive drugs.
AB  - We examined the effects of rimcazole, a specific antagonist of sigma sites, on
      the antitussive effects of dextromethorphan and noscapine in mice.
      Intraperitoneal injection of rimcazole, in doses from 1 to 10 mg/kg,
      significantly and dose dependently antagonized the cough depressant effect of
      N,N'-di(orthotolyl)guanidine (DTG), a sigma ligand. The cough depressant effects
      of dextromethorphan (3 mg/kg i.p.) and noscapine (10 mg/kg i.p.) were also
      significantly and dose dependently reduced by pretreatment with rimcazole.
      However, rimcazole (10 mg/kg i.p.) did not have a significant effect on the
      antitussive effect of morphine (3 mg/kg i.p.). Furthermore, rimcazole by itself
      (10 and 30 mg/kg i.p.) had no significant effect on the number of coughs. These
      results suggest that sigma sites may be involved in the antitussive mechanism of
      centrally acting non-narcotic antitussive drugs.

PMID- 8253119
TI  - Effects of nifedipine and TMB-8 on renal vasoconstriction induced by hypertonic
      saline in dogs.
AB  - Intrarenal arterial infusion of hypertonic saline (+30 mEq/l NaCl in renal
      plasma) reduced renal blood flow and glomerular filtration rate with little
      change in filtration fraction in anesthetized dogs. The blood flow and the
      filtration rate responses were suppressed during infusion of nifedipine (0.1
      microgram/kg per min). TMB-8 (50 micrograms/kg per min) also suppressed the blood
      flow response but not the filtration rate response. These results suggest that
      preglomerular vasoconstriction during hypertonic saline infusion requires Ca2+
      influx via voltage-dependent Ca2+ channels and that hypertonic saline slightly
      contracts postglomerular vessels by activating a TMB-8-sensitive Ca2+ movement
      pathway.

PMID- 8253120
TI  - Labelling of 5-HT3 receptor recognition sites in the rat brain using the agonist
      radioligand [3H]meta-chlorophenylbiguanide.
AB  - The binding of the tritiated derivative of the 5-HT3 receptor agonist meta
      chlorophenylbiguanide ([3H]mCPBG) to rat cortical homogenates and whole rat brain
      sections was assessed in an attempt to further investigate the binding of
      agonists to the 5-HT3 receptor. In crude homogenates of rat cortex, no
      reproducible specific [3H]mCPBG (1.0 nM) binding (defined by either 10 microM
      granisetron, 100 microM 5-HT or 100 nM 'cold' mCPBG) was detected. Using
      autoradiographic techniques, in rat hindbrain sections, [3H]mCPBG (1.0 nM)
      labelled a differential distribution of specific binding sites (defined by the
      inclusion of granisetron, 1.0 microM). Specific binding was only detected within
      the dorsal vagal complex (nucleus tractus solitarius, area postrema and dorsal
      motor nucleus of the vagus nerve). An identical distribution of specific binding
      was detected in adjacent sections incubated with the selective 5-HT3 receptor
      radioligand, [3H](S)-zacopride (0.5 nM; non-specific binding defined by the
      inclusion of granisetron, 1.0 microM). No reproducible specific [3H]mCPBG (1.0
      nM) binding (defined by the inclusion of granisetron, 1.0 microM) was detected
      within the rat forebrain. In contrast, [3H](S)-zacopride (0.5 nM) labelled
      specific sites (defined by the inclusion of granisetron, 1.0 microM) in some
      limbic brain structures (e.g. cerebral cortex, hippocampus, amygdala). These
      studies indicate that [3H]mCPBG labels the 5-HT3 receptor in rat brain tissue.
      However, the relatively high level of non-specific binding associated with this
      radioligand appears to mask the specific binding in regions which do not express
      relatively high densities of the 5-HT3 receptor.

PMID- 8253121
TI  - Inhibition of Ca2+ current in ileal cells by cyclopiazonic acid and ryanodine.
AB  - The effects of cyclopiazonic acid and its combination with ryanodine on the
      inward Ca2+ current (ICa) were investigated in smooth muscle cells isolated from
      the circular layer of guinea-pig ileum. The ICa of these cells exhibited two
      components: a low-threshold, nicardipine (5 microM)-resistant, fast-inactivating
      component and a high-threshold, nicardipine-blockable and slowly inactivating
      component. Neither cyclopiazonic acid (up to 10 microM) nor ryanodine (10 microM)
      was able to affect both these components of ICa, when applied separately.
      Cyclopiazonic acid and ryanodine combination led to total abolishment of the high
      threshold component, leaving the low-threshold component unaffected. The data
      presented suggest a process of Ca(2+)-dependent inactivation of the high
      threshold component, elicited by an increase in the subplasmalemmal Ca2+
      concentration due to Ca2+ released from the sarcoplasmic reticulum. It is
      considered that the combination of cyclopiazonic acid and ryanodine can be used
      as a valuable method to study the calcium sensitivity of both components of the
      ICa.

PMID- 8253122
TI  - Structure-activity relationship of 2-(ar) alkoxyadenosines at the adenosine A2
      receptor in coronary artery.
AB  - We examined the ability of four 2-(ar)alkoxyadenosines (2-(2
      phenylethoxy)adenosine, PEA; 2-[2-(2-naphthyl)ethoxy]adenosine, NEA; 2-[2-(4
      methylphenyl)ethoxy]adenosine, mPEA; 2-(1-hexyloxy)adenosine, HOA) to relax
      porcine coronary artery in vitro. All four compounds produced concentration
      dependent relaxations in rings contracted with 30 mM KCl. The EC25 values are as
      follows (x 10(-9) mol/l): CGS21680, (2-[p-(2-carboxyethyl)phenethylamino]-5'-N
      ethylcarboxamidoadenosi ne) (32.7) approximately NECA, 5'-N
      ethylcarboxamidoadenosine (51.4) approximately mPEA (74.3) approximately NEA
      (160.7) > HOA (855.1) approximately PEA (1259) approximately 2-chloroadenosine
      (1871) > adenosine (9705). However, EC75 values for all the compounds except
      adenosine and 2-chloroadenosine converged to a range of 8.16 to 22.86 microM,
      suggesting a biphasic response. Furthermore, the responses were found to be
      independent of endothelial integrity. The unselective adenosine receptor
      antagonist 8-p-sulphophenyltheophylline (100 microM) attenuated the relaxant
      response to NEA (EC25 = 1172 nM), suggesting that adenosine receptors mediated
      relaxation. Structure-activity correlations suggest that the adenosine A2
      receptor in porcine coronary artery contains a region of limited bulk tolerance
      juxtaposed to the region occupied by adenine C-2 and distal to that a large
      hydrophobic region.

PMID- 8253123
TI  - [125I]azido-DTLET as a tool for selective covalent labeling of delta-opioid
      receptors in rat brain sections.
AB  - The binding kinetics and pharmacological selectivity of the photoaffinity delta
      opioid ligand [125I]azido-DTLET (Tyr-D-Thr-Gly-Phe(pN3)-Leu-Thr) were
      investigated in serial frozen sections from rat neostriatum prior to ultraviolet
      irradiation (i.e., in conditions of reversibility). Scatchard analysis of
      saturation binding experiments indicated that [125I]azido-DTLET binds to both a
      high (KD = 5.04 nM) and a low (KD = 38 nM) affinity site. Binding to the low
      affinity site was no longer detectable in the presence of unlabeled [D-Ala2,N
      MePhe4,Gly-Ol5]enkephalin (DAGO), suggesting that this site corresponds to mu
      opioid receptors. This interpretation was further supported by the dose-dependent
      inhibition of the binding of [3H]DAGO by non-radioactive azido-DTLET. Binding to
      the high-affinity site was totally inhibited, in a dose-dependent fashion, by a
      variety of opioid drugs among which delta-opioid ligands showed the highest order
      of potency. It is concluded that, in the nanomolar range, [125I]azido-DTLET
      constitutes a highly selective tool for covalent labeling of delta-opioid
      receptors in rat brain sections.

PMID- 8253124
TI  - Contraction and relaxation of aortas from galactosaemic rats and the effects of
      aldose reductase inhibition.
AB  - Rats were fed for 10 days with a 40% galactose diet, in order to chronically
      stimulate the polyol pathway. Thoracic aorta contraction and relaxation were
      studied. Compared to controls, galactosaemia did not influence contractions to
      phenylephrine or serotonin. Acetylcholine produced concentration-dependent
      relaxation of aortic rectangles precontracted with phenylephrine; galactosaemia
      caused a 25% deficit in maximum relaxation to acetylcholine (P < 0.01) and a 168%
      increase in EC50. There was a similar 25% reduction in relaxation to 3 microM
      calcium ionophore A23187 (P < 0.05). By contrast, there were no significant
      differences in endothelium-independent relaxation to nitroglycerine or
      cromakalim. The abnormalities in endothelium-dependent relaxation were completely
      prevented by treating galactosaemic rats with the aldose reductase inhibitor,
      ponalrestat. Thus, the data demonstrate that elevated polyol pathway activity
      contributes to reduced endothelium production, release or the action of nitric
      oxide in experimental galactosaemia, and suggest that this mechanism could also
      contribute to the vascular defects seen in diabetes mellitus.

PMID- 8253125
TI  - Cholera toxin antagonizes morphine-induced catalepsy through a cyclic AMP
      independent mechanism.
AB  - We studied the effect of intracerebroventricular pretreatment with pertussis
      toxin and cholera toxin on morphine catalepsy in rats. Pertussis toxin (1
      micrograms/rat, two, three and six days before) did not affect catalepsy evoked
      by central morphine. Cholera toxin (1 micrograms/rat) did not affect morphine
      catalepsy after 24 h and 48 h, but significantly reduced it (about 60%) after
      three and five days. Ten days later the morphine response had totally recovered.
      This effect was selective, since morphine analgesia was not modified. The
      reduction of catalepsy appeared unrelated to the ability of cholera toxin to
      raise cAMP levels, as demonstrated by the different time course of changes in
      striatal cholera toxin-stimulated adenylate cyclase activity. The effect required
      an intact cholera toxin molecule and did not occur with a similar dose of cholera
      toxin-B subunit. These findings demonstrate that catalepsy is an opioid effect
      not linked to pertussis toxin-sensitive G proteins and suggest that the Gs
      protein might be involved.

PMID- 8253126
TI  - Characterization of [3H]meta-chlorophenylbiguanide binding to 5-HT3 receptors in
      N1E-115 neuroblastoma cells.
AB  - The binding characteristics of a radiolabelled 5-HT3 receptor agonist, [3H]meta
      chlorophenylbiguanide (mCPBG), were examined in membranes from N1E-115
      neuroblastoma cells. Scatchard plots of saturation binding data showed the
      presence of two populations of binding sites, with Kd = 0.03 +/- 0.01 nM and 4.4
      +/- 1.2 nM and Bmax = 11.9 +/- 4.2 and 897.9 +/- 184.7 fmol/mg protein
      respectively. Competition studies with a selection of agonists and antagonists
      revealed the pharmacological profile expected for a 5-HT3 receptor. The rank
      order of potency for antagonists was granisetron > quipazine > GR65630 >
      ondansetron > MDL72222, and for agonists was mCPBG > 5-HT (5-hydroxytryptamine,
      serotonin) > 2-methyl-5-HT. IC50 values for 5-HT and 2-methyl-5-HT were lower
      than those observed using radiolabelled antagonists, and combined with functional
      experiments, the data suggest that [3H]mCPBG may label high affinity desensitized
      states of the receptor. We conclude that [3H]mCPBG labels 5-HT3 receptors in N1E
      115 neuroblastoma cell membranes and may be a useful compound with which to
      explore 5-HT3 receptors in other systems.

PMID- 8253127
TI  - The development of behavioral sensitization to apomorphine is blocked by MK-801.
AB  - The effects of the non-competitive NMDA receptor antagonist, MK-801
      (dizocilpine), on the development of sensitization to the mixed dopamine receptor
      agonist, apomorphine were examined. Rats pretreated with MK-801 (0.25 mg/kg)
      prior to 2.0 mg/kg apomorphine failed to show a progressive sensitization to the
      activating effect of apomorphine across six preexposure sessions, nor did they
      show enhanced activity relative to control rats in response to 0.5 mg/kg
      apomorphine, given alone, during a subsequent test for sensitization. These
      results support the view that MK-801 interferes with long-term neural changes
      underlying sensitization to stimulant drugs.

PMID- 8253128
TI  - Nitric oxide modulates Ca2+ channel currents in rat sympathetic neurons.
AB  - The effects of nitric oxide on the Ca2+ channel currents of adult rat superior
      cervical ganglion neurons were investigated using the whole-cell patch-clamp
      technique. Nitric oxide-containing compounds sodium nitroprusside and S-nitroso-N
      acetyl-penicillamine increased the amplitude of Ca2+ currents by intracellular
      application. In addition, both sodium nitroprusside and S-nitroso-N
      acetylpenicillamine reduced norepinephrine-induced inhibition of Ca2+ currents.
      The results suggest that nitric oxide might be involved in the modulation of
      Ca(2+)-dependent neurotransmission in sympathetic neurons.

PMID- 8253129
TI  - A semisynthetic glycosphingolipid (LIGA20) reduces 2,4, 5-trihydroxyphenylalanine
      neurotoxicity in primary neuronal cultures.
AB  - The semisynthetic glycosphingolipid derivative II3Neu5-AcGgOse4-2-d-erythro-1,3
      dihydroxy-2-chloro-acetamid e-4-trans- octadacene (LIGA20) attenuated injury
      induced by the excitotoxic L-dopa metabolite 2,4,5-trihydroxyphenylalanine (TOPA)
      in cultures of rat cerebellar granule cells when presented simultaneously with
      TOPA (EC50; 9 microM LIGA20). The natural glycosphingolipid ganglioside GM1 up to
      200 microM was not neuroprotective as cotreatment, although pretreatment of cells
      for 2 h was efficacious. This greater potency and speed of LIGA20 action extended
      to limiting TOPA-induced death of cultured mesencephalic dopaminergic neurons.
      These data suggest that LIGA20 may have therapeutic potential for the treatment
      of disorders associated with excitotoxic processes.

PMID- 8253130
TI  - Effects of dothiepin on nociceptive flexion reflex and diffuse noxious inhibitory
      controls in humans.
AB  - The analgesic activity of dothiepin (an antidepressant interacting with serotonin
      receptors) was studied (double-blind) in humans. A significant increase in
      nociceptive flexion reflex threshold and subjective pain threshold was observed
      after a 14-day dothiepin treatment. The effects of dothiepin on diffuse noxious
      inhibitory controls were also investigated using the cold-pressor test as
      conditioning stimuli. After dothiepin a reduced inhibition of nociceptive flexion
      reflex during the cold-pressor test and a significant facilitation immediately
      after the cold-pressor test were observed, while the subjective pain perception
      was normally inhibited. Our data suggest a serotonergic modulation of diffuse
      noxious inhibitory controls in humans.

PMID- 8253131
TI  - [Differences in susceptibility of mice among various strains to oral infection
      with Corynebacterium kutscheri].
AB  - Differences in susceptibility of female mice among 10 strains to Corynebacterium
      kutscheri infection were studied pathologically and bacteriologically. Twenty
      mice of each strain were inoculated orally with 4 x 10(5.0) CFU of the bacteria.
      The gross lesions were observed in 60.0% of BALB/c-nu/nu mice, 25.0% of CBA/N
      mice, 10.0% of MPS mice, and 5.0% of A/J and C3H/He mice, while BALB/cCr,
      C57BL/6Cr, B10.BR/SgSn, ddY and ICR mice showed neither clinical signs nor gross
      lesions. Six BALB/c-nu/nu, two CBA/N and one MPS mice died within 15 days after
      inoculation. C. kutscheri was recovered from 95.0% of BALB/c-nu/nu mice, followed
      by 75.0% of A/J mice, 65.0% of CBA/N mice, 55.0% of MPS and BALB/cCr mice, and
      30% of C3H/He mice. On the other hand, from C57BL/6Cr, B10.BR/SgSn and ddY mice,
      the bacteria were recovered at less than 15.0% of the mice. No bacteria were
      recovered from ICR mice. C. kutscheri colonized most frequently in the cecum,
      colon and rectum. Number of mice having agglutinating antibodies were less than
      20% and their antibody titers ranged from 1:10 to 1:80. These results indicated
      that there were differences in susceptibility of mice among the strains to oral
      infection of C. kutscheri. Namely, BALB/c-nu/nu, A/J, CBA/N, MPS and BALB/cCr
      mice appeared to be susceptible, and C3H/He mice intermediate, while C57BL/6Cr,
      B10.BR/SgSn, ddY and ICR resistant. BALB/c-nu/nu mice were most susceptible and
      exhibited markedly severe disease by the infection.

PMID- 8253132
TI  - [Invention of an air forced ventilated micro-isolation cage and rack system-
      environment within the cages: ventilation, air flow].
AB  - A forced air ventilation system for small laboratory animals was developed. The
      system consists of an air handling unit with air supply and exhaust fans, a rack,
      hard cage covers with a large diameter air inlet and an outlet, and shoe box
      cages. Air flow from the supply duct, to the exhaust duct and within the cage
      were observed. Variations in air flow among cages was minimal. The optimal air
      exchange rate of the cages in this system was determined to be 60 times per hour
      based on the results obtained in the present study. At this air exchange rate,
      air flow at the base of the cages had a velocity of less than 0.09m/sec, which
      was within the range of recommended values for humans. The observed results show
      that the system developed is capable of sustaining a laboratory animal
      microenvironment well in terms of air flow, without too much energy cost.

PMID- 8253133
TI  - [Early lesions of pancreatic islets in small-ob mice (C57BL/6J-ob/ob)].
AB  - Pancreatic islets of C57BL/6J-ob mice were microscopically examined at the ages
      of 5, 13, and 21 days, to clarify the time of the increase in number of A-cells,
      which appears to lead to diabetic symptoms in Small-ob mice (C57BL/6J-ob/ob). The
      findings of islet in 5-day-old C57BL/6J-ob mice were the same as those of
      C57BL/6J-+/+ mice. At 13 days of age, changes in islet of C57BL/6J-ob mice were
      classified into 3 groups. They were no significant changes (putative normal),
      hypertrophic B-cells with clear cytoplasm (Ob mice), and an increase of A-cells
      (Small-ob mice), respectively. Electron microscopically, a tendency toward
      dilatation of endoplasmic reticulum was found in the hypertrophic B-cells. In the
      islets that had an increase in number of A-cells, only a few vacuoles, which were
      suggestive of degranulation, were found in the cytoplasm of B-cells, and
      premature secretory granules were seen in the A-cells. In part of the A-cells,
      development of rough-surfaced endoplasmic reticulum was also seen. Mild
      hypertrophy of the islets and the B-cells were observed in more non-diabetic Ob
      mice at the age of 21 days than non-obese mice at the same age, and only 2 of 6
      mice had the increase in number of A-cells. In Small-ob mice, the increase in
      number of A-cells was more obvious than in the diabetic Ob mice, while other
      islet findings were similar to those of non-obese mice in extent.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8253134
TI  - [An application of in vitro fertilization--embryo culture--embryo transfer system
      on the drug safety evaluation: fertility test of male mice administered with the
      anticancer drug].
AB  - We examined an application of in vitro fertilization--embryo culture--embryo
      transfer system for reproductive and developmental study on the drug safety
      evaluation in mice. The male mice at 10 weeks of age were administered
      intravenously with a single dose of 75 mg/kg of the anticancer platinum complex
      (DWA 2114R) which inhibits DNA synthesis. Four to six weeks after administration,
      the males were mated with the superovulated females. Fertilization rates were
      significantly lower than the controls at each weeks after the administration.
      Furthermore, delayed formation of pronucleus was observed as compared with the
      control. Four weeks after administration, the preimplantation development to
      blastocyst stage of those embryos in vitro and the survival rates on the day 17
      of gestation after embryo transfer suggested that a DNA synthesis in germ cells
      during maturation was inhibited and/or prevented by DWA 2114R. The results of in
      vitro fertilization reflected its sperm concentration rather than the
      administration of DWA 2114R. Thus, an analysis of the delayed formation of
      pronucleus observed fertilization in vivo could not done in detail. To use for
      the drug safety evaluation, there exist plenty of room for improvement in this
      system. These results have showed that the embryo culture and the embryo transfer
      are useful techniques as the reproductive and developmental study on the drug
      safety evaluation. These techniques bring additional informations on the pre- and
      post-implantation development in vivo.

PMID- 8253135
TI  - [Estimation of nitrogen-corrected metabolizable energy value of laboratory canine
      diets].
AB  - This study evaluates the reliability of the equation, metabolizable energy (ME) =
      digestible energy (DE) - 1.25 x digestible crude protein (DCP), as a means of
      estimating the energy value of non-purified diets for laboratory dogs. To do
      this, five digestion and nitrogen-balance (NB) trials and determination of the
      energy value of a diet were conducted using five diets and four mature, male
      Beagles for each experiment. The resulting digestibility of crude protein, acid
      ether extract, and nitrogen-free extract of these diets were 79.5%, 91.6%, and
      84.8%, respectively. The NB in every diet was positive: 1.4-8.6 mg/g dry matter
      of ingested diet. Of the nitrogen (N) ingested, 21% was excreted into feces, 66%
      was excreted into urine, and 13% was retained. In terms of dietary gross energy
      (GE), 18% was lost in feces and 5% was excreted into urine leaving 77% as ME.
      Retained energy in the body was only 1%, and N-corrected metabolizable energy
      (MEn) was 76% of GE. The average urinary energy (UE) loss per gram of urinary N
      was 7.84kcal. The correlation between UE/DCP and NB values is statistically
      significant: UE/DCP = 1.24-0.03NB, r = 0.798, P < 0.001. Therefore, UE/DCP is
      1.24kcal/g at N-equilibrium, almost the same as the factor in the above equation.
      The ME value calculated by the equation is identical to the MEn value and both
      are significantly lower (P < 0.05) than the empirically determined ME
      value.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253136
TI  - [Copulatory behavior after ectopic pituitary grafting in male rats].
AB  - It is known that suppression of copulatory behavior observed in aged male animals
      is due to elevate prolactin levels, the so-called hyperprolactinemia, found in
      these animals. The present study was done to determine whether hyperprolactinemia
      can modify the copulatory behavior of young adult male rats. Hyperprolactinemia
      was induced by grafting one or two pituitary glands of adult males of the same
      strain under the kidney capsules of each sexually experienced male. Grafted
      animals exhibited suppressed copulatory behavior patterns when tested one month
      after pituitary transplantation. The animals given two pituitary grafts differed
      from the sham-operated controls in latency to intromit (P < 0.05), as well as in
      the numbers of intromission (P < 0.05) and ejaculation (P < 0.01). After tests of
      copulatory behavior, serum concentrations of LH, FSH, prolactin and testosterone
      were measured by radioimmunoassay. Serum levels of prolactin were significantly
      increased (P < 0.05) in the animals given 2 grafts, compared with sham-operated
      controls. From these results, suppression of copulatory behavior in the young
      adult animals grafted was similar to that in aged adults. The findings suggest
      that decline of copulatory behavior with increasing age results from chronic
      elevation of prolactin.

PMID- 8253137
TI  - Effects of the contents of dietary crude protein on growth rate and NK activity.
AB  - The relationship between body weight gain and food intake was examined using 3
      strains of mice, C3H/He, C57BL/6 and A/J mice, that were fed 4 kinds of diets
      differing in crude protein contents. Body weight gain of the mice fed the diet
      containing 3% protein was extremely small, while that of the mice fed the diet
      containing 40% protein was smaller than that of the mice fed the diet containing
      10% or 20% protein. Mice were shown to possess a characteristic ability to intake
      an almost constant amount of calories irrespective of crude protein contents in
      diets, with some exceptions. These experimental results indicate that crude
      protein intake plays an important role for body weight gain. It was also assumed
      that energy consumption in C57BL/6 mice fed the 40% protein diet was accelerated
      because of excessive protein intake. Normal NK activity and antibody responses to
      SRBC were maintained at the age of 12 weeks in all the strains of mice fed the
      different diets.

PMID- 8253138
TI  - Vascular architecture of 3-methyl choranthrene-induced rat fibrosarcoma
      demonstrated by scanning electron microscopy of resin casts.
AB  - A detailed knowledge of the vascular system of tumors is requisite to a clear
      understanding of tumor physiology and pathology. Accordingly, in this study,
      examination was made of the vascular architecture of rat fibrosarcomas induced by
      3-methyl choranthrene by scanning electron microscopy of resin casts to observe
      the three-dimensional vascular pattern of the sarcoma. The results were compared
      with those of corresponding serial sections of India ink-injected tissue. The
      major arteries in and around tumors appeared devoid of intra-arterial cushions
      which regulate blood flow. The arterial lining of resin casts was smooth just at
      the site where it entered the tumor. This may possibly be indication of
      degeneration and loss of the smooth muscle layer in the vascular wall. Casts of
      capillaries were very thin from 4 to 6 microns in diameter and very few sprouts
      could be seen. Capillaries, frequently present in superficial regions of the
      tumor, formed a rich irregular fine polygonal network. In fibrous tissue in
      deeper regions of the tumor, this network was coarse. The absence of intra
      arterial cushions and degeneration of muscle cells may thus possibly be the
      reason for the characteristic haemodynamics of tumors.

PMID- 8253139
TI  - [Ontogeny of the pronephros and mesonephros in the South African clawed frog,
      Xenopus laevis Daudin, with special reference to the appearance and movement of
      the renin-immunopositive cells].
AB  - Development of the pronephros and mesonephros of Xenopus laevis was
      morphologically studied in the larvae immediately after hatch (stage 35/36) to
      the end of metamorphosis (stage 66) together with the appearance of renin
      immunopositive cells. The pronephros consisted of 3 pairs of pronephric tubules
      at stage 35/36 and became functional at stage 37/38 with the opening of the
      pronephric ducts to the cloaca. It increased thereafter in volume, but became
      degenerative at stage 56, lost a part of the pronephric ducts at stage 60, and
      completely disappeared at stage 64. The mesonephros displayed its anlage at stage
      42, and gained the immature renal corpuscles at stage 48. At stage 49, it was
      equipped with the matured nephrons. The mesonephric tubules differentiated into
      the neck, proximal, intermediate and distal parts. The collecting tubules and
      ducts were also observed at this stage. At stage 56, a part of the mesonephric
      tubules degenerated and were displaced by newly formed tubules. Reorganization of
      the mesonephros was not completed at the end of metamorphosis. Renin
      immunopositive cells did not appear in the pronephros, but were observed at the
      diverging part of the renal artery from the dorsal aorta, and in the walls of
      arteries and afferent arterioles within the mesonephros in a low frequency of
      appearance.

PMID- 8253141
TI  - [Morphology of the scent gland in the vole].
AB  - The presence of the scent glands were examined macroscopically and histologically
      in the Japanese vole, Microtus montebelli and the Hungarian vole, Microtus
      arvalis. A pair of scent glands were observed on the buttocks of the Japanese
      vole as the oval nodules with yellowish colored skin. The size of the glands was
      larger in males than in females. Histologically, the glands were composed of the
      aggregation of many acini of sebaceous glands. The epidermis above the scent
      glands were thicker than that in the other areas. In the Hungarian vole, no such
      gland could be detected with macroscopical and histological examinations.

PMID- 8253140
TI  - Coprophagy in rabbits: autoingestion of hard feces.
AB  - The rabbit is a representative animal species that conducts coprophagy, i. e. the
      production and reingestion of soft feces. We, however, encountered a maternal
      rabbit eating its own hard feces. A detailed investigation was performed on
      coprophagy in the rabbit to elucidate whether rabbits actually reingest their own
      hard feces. It was found that young adult Japanese White rabbits reingested their
      hard, as well as soft, feces directly from the anus. It has been reported that
      rabbits reingest only soft feces because of their high nutritive content, but the
      present study demonstrates that rabbits also reingest their hard feces despite
      their low nutritive content. It seems possible that coprophagy may be initiated
      by the colonic or rectal wall expanding effects of the fecal material itself.

PMID- 8253142
TI  - A new method of long-term bile collection from unrestrained dogs.
AB  - A method of long-term bile collection from unrestrained dogs was developed. A
      steel needle was passed subcutaneously from the animal's right side into the
      abdomen. A catheter, threaded through this needle, was inserted from the side and
      brought out below the abdomen. The catheter was introduced into the common bile
      duct and a vest was then fitted on the dog. The external catheter tip was placed
      in a collection bottle in the pocket of the vest. This method allows the animal
      to move freely in its cage. The bile of an unrestrained dog weighing 10 kg was
      collected for 3 weeks at an output rate of 4.2-4.6ml per hour.

PMID- 8253143
TI  - In vitro development of two-cell embryos obtained from female mice of different
      ages.
AB  - Female mice of the IVCS strain (ddN origin), aged 90, 180, 240, 270 and 300 days,
      were used in this experiment. The percentages of fertilized ova per ova collected
      from the oviducts, on Day 1 of pregnancy, of mice aged 90 and 180 days were 100%
      and 91.1%, respectively. Significantly decreased rates of fertilized ova were
      observed in mice aged 240 to 300 days as compared to 90-day-old controls (P <
      0.05). Almost all two-cell embryos collected from 90- to 270-day-old mice
      developed into blastocysts or expanded blastocysts, and the developmental rate
      from 2-cell embryo to hatched blastocyst then decreased significantly (P < 0.05).
      The developmental rate from 2-cell embryo to hatched blastocyst also decreased
      significantly in 300-day-old mice (P < 0.05). These results demonstrate
      differences in the viability of mouse embryos collected from mice of different
      ages.

PMID- 8253144
TI  - Usefulness of alpha 1 acid glycoprotein (alpha 1-AG) values in screening pound
      dogs acquired from animal shelters for experimental use.
AB  - The usefulness of alpha 1 acid glycoprotein (alpha 1-AG) levels in selecting
      pound dogs from animal shelters for experimental use, was assessed in 1,013 dogs.
      The mean (+/- SD), minimum, and maximum alpha 1-AG values were 375.9 (+/- 244.8),
      20, and 1,650 micrograms/ml. The alpha 1-AG value exceeded 500 micrograms/ml, the
      cut-off value for the normal range, in 219 dogs. There was little correlation
      between alpha 1-AG values and any of 15 blood chemistry parameters or with
      hematocrit values. Of the 176 dogs that died within 2 weeks after arrival at our
      institution, the alpha 1-AG concentration was abnormal in one-third. These
      findings confirm that measurement of alpha 1-AG is extremely useful in
      identifying desperate dogs and in confirming of the prognosis.

PMID- 8253145
TI  - The similar mammary tumour potentials in virgins and breeders of SHN mice.
AB  - Spontaneous mammary tumour potential was compared between virgins and breeders of
      a high mammary tumour strain of SHN mice. Virgins were essentially similar to
      breeders in both the cumulative and the monthly incidences of mammary tumours.
      DNA synthesizing enzyme activities and the number and the weight of mammary
      tumours also differed little between groups. While the number of preneoplastic
      mammary hyperplastic alveolar nodules (HAN) was significantly higher in breeders
      than in virgins, little difference was observed between groups in the end-bud
      formation and the duct growth of normal glands and the growth of HAN. These
      results indicate that in SHN mice virgins have similar mammary tumour potential
      to breeders, which is much advantageous for practical use of this strain as an
      animal model for human breast and other types of cancers.

PMID- 8253146
TI  - Indirect measurement for body surface area of cotton rats.
AB  - The body surface areas (BSAs) of 42 cotton rats (21 females weighing 29.08 to
      169.60 g, and 21 males weighing 18.93 to 168.03 g) were measured. From these
      areas and body weights (BW), the equation, BSA (cm2) = 47.66 + 2.476 x BW (g) 
      0.006 x BW (g)2, was derived. To verify the applicability of the equation, the
      BSAs of another 19 animals (12 females weighing 29.08 to 169.60 g, and 7 males
      weighing 19.27 to 167.32 g) were calculated and the values compared with the
      measured BSAs. The correlation between calculated and measured BSAs was
      significant (r = 0.995, P < 0.01). Therefore, this equation can be used to
      calculate cotton rat BSA.

PMID- 8253147
TI  - Growth of the mammary gland in rhino mouse.
AB  - The rhino mouse, so called because of its characteristic rhinocerous-like skin
      cannot raise its young. Although the animal has rudimentary mammary glands, these
      are thought to be defective due to their impossibility to raise their young.
      Morphological observations of the female mammary glands of rhino mice (hrrh/hrrh)
      were carried out and the results were compared with those of their normal litter
      mates (hrrh/+) at various ages from 1 month to 1 year. No morphological
      differences in mammary gland development was seen between the rhino mice and
      their normal litter mates, and normal secretory changes were observed in the
      rhino mice after delivery. Mouse mammary tumor virus (MMTV) expression and the
      occurrence of hyperplastic alveolar nodule (HAN) were analogous to these features
      in phenotypically normal hrrh/+ mice. Further, the sweat glands in the rhino
      mouse were normal. Thus, anomalies in the rhino mouse appeared to be limited to
      the skin and pilosebaceous apparatus.

PMID- 8253148
TI  - [Age-associated changes of cytokine levels in bone marrow of Wistar rat].
AB  - Cytokine levels of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1
      beta), interleukin-3 (IL-3), interleukin-6 (IL-6), erythropoietin (EPO) and tumor
      necrosis factor alpha (TNF alpha) in bone marrow of Wistar rat were measured with
      immunofluorescent assay. The levels of IL-1 alpha, IL-1 beta, IL-3, IL-6 and EPO
      were high in young (4 weeks old), and gradually decreased thereafter. In
      contrast, TNF alpha level in bone marrow was low by 18 weeks old and high at 26
      and 52 weeks old. These results indicated that age-associated changes of bone
      marrow cell composition in rat are well correlated with the levels of cytokine
      related to bone marrow cell differentiation.

PMID- 8253149
TI  - [Age-related changes in the visual function of WBN/Kob rats: a behavioral study].
AB  - Changes in visual function with increasing age were studied in male WBN/Kob rats,
      a new diabetic strain. In order to detect visual abnormalities in WBN/Kob rats, 5
      WBN/Kob and 5 Wistar/ST (control) rats from each group were examined at 5, 9, 13,
      17, 23, 27, 36, 45, 54, 67 and 80 weeks of age using dark and light distinction
      and open-field tests. The rates at which WBN/Kob rats selected the dark area were
      85.0 to 100%, 58.8% and 52.6% at 5 to 54, 67 and 80 weeks of age, respectively,
      while those for Wistar/ST rats were 85.0 to 100% in each age group. Visual
      abnormality was obvious in WBN/Kob rats aged 67 and 80 weeks, compared with
      Wistar/ST rats (P < 0.05). There were no significant signs of visual abnormality
      in the open-field test. Detection of visual abnormality seems to be possible from
      67 weeks of age.

PMID- 8253150
TI  - Hematological standard values in the cotton rat (Sigmodon hispidus).
AB  - The purpose of this study is to establish reference data on several hematological
      parameters in the cotton rat. Eight hematological values were measured in 28
      males and 29 females at 16 to 18 weeks of age. Females showed significantly lower
      RBC, Ht and MCV values than males. Female Hb and PLT values tended to be lower
      than male values, although differences did not reach a conventional level of
      significance. WBC and PLT values varied widely in both sexes.

PMID- 8253151
TI  - [Animals used in experiments in Japan (1956-90)].

PMID- 8253152
TI  - Trypanosoma evansi: in vivo and in vitro determination of trypanocide resistance
      profiles.
AB  - We have determined the in vivo and in vitro sensitivities to six common
      trypanocides of two groups of trypanosomes, (1) two Trypanosoma equiperdum clones
      and three Trypanosoma evansi clones originating from Asia, Latin America, and
      Africa; and (2) six laboratory-derived drug-resistant subclones from two of the
      T. evansi and one of the T. equiperdum clones. We found that (1) we could induce
      trypanocide resistance by successive passage through mice treated with
      subtherapeutic doses of drugs; (2) clones selected for resistance to berenil and
      cymelarsan are not cross-resistant to suramin; (3) clones resistant to berenil,
      cymelarsan, and suramin are more sensitive to quinapyramine in vivo than the
      parental clones; (4) berenil resistance is stable; (5) some berenil-resistant
      clones acquire resistance to cymelarsan; (6) in vivo resistance to isometamidium
      is not detectable in vitro; and (7) the in vitro sensitivities to berenil and
      cymelarsan of parental clones and their laboratory-derived resistant subclones
      generally agreed with the in vivo results. We conclude that with further
      refinement the in vitro assay procedure may be useful for rapid determination of
      the sensitivity of trypanosome isolates to some current drugs and for screening
      new trypanocides. Our data also raise the possibility that conventional treatment
      regimens should be reevaluated and support the presence of at least two drug
      resistance mechanisms in T. evansi and T. equiperdum, single drug resistance
      (berenil), and cross-resistance (berenil and cymelarsan).

PMID- 8253153
TI  - Brugia pahangi: effects of protective resistance on lymphatic lesions and
      granulomatous inflammation in infected jirds (Meriones unguiculatus).
AB  - Effects of protective resistance on lymphatic lesions and granulomatous
      inflammation in infected jirds (Meriones unguiculatus). Experimental Parasitology
      77, 395-404. The hypothesis that protective immune responses play a role in the
      induction of filarial-associated lymphatic lesions was tested in jirds immunized
      twice with 75 Brugia pahangi radiation-attenuated third-stage larvae. Lymphatic
      lesions and granulomatous reactivity were compared in immunized, infected, and
      naive jirds at both acute and chronic periods following challenge with 100 third
      stage larvae. Challenge worm burdens were reduced in immunized jirds at both
      infection periods. The ratio of lymph thrombi to lymphatic worms, an indicator of
      lymphatic lesion severity, was significantly greater in immunized jirds than in
      nonimmunized-challenged jirds during acute but not chronic infections. Parasite
      specific-granulomatous hypersensitivity was assessed by measurements of granuloma
      areas around B. pahangi-soluble adult worm antigen-coated sepharose beads
      embolized in the lungs prior to necropsy. Marked granulomatous inflammatory
      responses seen during the acute period in both immunized-challenged and
      nonimmunized-challenged jirds were significantly reduced in similar jirds during
      chronic periods. Jirds with existing B. pahangi infections were not resistant to
      homologous challenge infection and had fewer lymphatic lesions and reduced
      granulomatous inflammatory responses to soluble adult worm antigen compared to
      previously naive jirds at acute periods postchallenge. These data suggest that
      protective immune responses increase the severity of filariae-induced lymphatic
      inflammation. The subsequent modulation of these lesions is probably associated
      with parasites that survived the protective immune response.

PMID- 8253154
TI  - Trypanosoma cruzi: antibody production and T cell response induced by stage
      specific surface glycoproteins purified from metacyclic trypomastigotes.
AB  - The main surface glycoproteins of metacyclic trypomastigotes of Trypanosoma
      cruzi, gp90, gp82, and gp35/50, were purified and the immune response elicited by
      these antigens was analyzed. Balb/c mice immunized with antibody-affinity
      purified gp82, plus alum as adjuvant, produced antibodies that recognized both
      the gp82 and the heterologous gp90 and gp35/50. On the other hand, antisera to
      gp90 reacted only with the homologous antigen, either by immunoprecipitation or
      by immunoblotting. Neither sera reacted with unrelated proteins in ELISA. Both
      antisera lysed 90-100% metacyclic forms in a complement-mediated reaction, a
      property associated with protection. However, in contrast to gp90, previously
      shown to induce protective immunity against acute T. cruzi infection, gp82 was
      not immunoprotective. Lymph node (LN) cells of mice primed with gp82 or gp90,
      which display 40% amino acid sequence identity at the carboxy terminal domain,
      were strongly stimulated in vitro by either one of these antigens. Proliferation,
      inhibitable by anti-CD4 but not by anti-CD8 antibodies, was T. cruzi-specific, no
      activation being observed with irrelevant antigens. LN cells of mice immunized
      with unrelated proteins did not proliferate in vitro in the presence of gp82 or
      gp90. The 35/50-kDa glycoconjugate, which was phenol-extracted, did not elicit
      any detectable antibody or T cell response.

PMID- 8253155
TI  - Onchocerca volvulus: characterization of an immunodominant hypodermal antigen
      present in adult and larval parasites.
AB  - Biochemical and immunological data suggest that a relatively limited number of
      polypeptide antigens of viable Onchocerca volvulus-infective larvae are available
      to be recognized by the host's immune system. A partial cDNA clone encoding one
      such antigen, designated lambda RAL-2, was isolated by screening an expression
      cDNA library with antisera raised against viable O. volvulus L3. The antigen
      encoded by this clone was subsequently found to be immunogenic in the majority of
      individuals exposed to O. volvulus. In the present study, the native antigen
      corresponding to lambda RAL-2 (Ov17) has been characterized. Immunolocalization
      and in situ hybridization techniques have been used to localize Ov17 in adult and
      larval stages of the parasite. In adult females, Ov17 was localized primarily in
      the hypodermis. Ov17 was accessible to surface labeling reagents in viable adult
      parasites. Full-length cDNA clones encoding Ov17 suggested that the nascent
      protein contains a putative leader sequence, which is almost immediately followed
      by a polyglutamine tract. Analysis of antibody reactivity to recombinant proteins
      containing and lacking the polyglutamine tract demonstrated that this structure
      was not a significant B cell epitope in individuals exposed to O. volvulus.

PMID- 8253156
TI  - Leishmania: immunochemical comparison of the secretory (extracellular) acid
      phosphatases from various species.
AB  - Promastigotes of all Leishmania species, except most Leishmania major stocks,
      synthesize and secrete extracellular soluble acid phosphatases [SAcP(s)] which
      are capable of dephosphorylating a wide range of substrates and, consequently, of
      modifying the parasite environment. To assess their antigenic/structural
      relatedness, the SAcP(s) from various species were compared immunochemically
      using both a monospecific rabbit antiserum and several monoclonal antibodies made
      against the purified promastigote SAcP of a cloned line of Leishmania donovani
      donovani. Results obtained from antibody-bridged enzyme activity assays
      demonstrated that these reagents quantitatively immunoprecipitated the enzymatic
      activities of SAcP(s) from 18 different W.H.O. reference stocks of Leishmania,
      including two L. major strains. Those results showed, for the first time, that
      all SAcP(s) possessed some common cross-reactive antigenic epitopes.
      Immunoprecipitates obtained from [35S]methionine, metabolically labeled
      promastigote culture supernatants of the various species, were analyzed by SDS
      PAGE/fluorography. These analyses showed that marked differences existed among
      the SAcP(s) both in their relative mobilities and the number of constituent bands
      resolved. Tunicamycin treatment resulted in a significant reduction in the
      apparent molecular weights of SAcP(s) from three different isolates, confirming
      the presence of N-linked carbohydrate side chains in these enzymes. In addition,
      the SAcP released by L. donovani intracellular amastigotes was also
      immunoprecipitated with the monospecific rabbit antisera from the culture
      supernatant of infected macrophages. Cumulatively, these data demonstrate that
      despite individual species variations, the SAcP(s) from all Leishmania tested
      have retained certain common antigenic/structural epitopes and functional protein
      domains. Such conservation among SAcP(s) suggests that this enzyme must play an
      essential role in the survival of promastigotes and amastigotes of all Leishmania
      species.

PMID- 8253157
TI  - Schistosoma mansoni: genetic complementation analysis shows that two independent
      hycanthone/oxamniquine-resistant strains are mutated in the same gene.
AB  - Two drug-resistant strains of Schistosoma mansoni were compared in this study in
      order to decide whether they are both mutated in the same gene with respect to
      drug-sensitive schistosomes. One of the two strains was isolated in the
      laboratory, while the other one originated from a treated uncured patient and was
      subsequently drug selected in the laboratory. The approach consisted in a genetic
      complementation test performed essentially by crossing the two strains and
      assessing resistance in the progeny. Since no reappearance of drug sensitivity
      was detected in the progeny, it was concluded that the two strains failed to
      complement and were therefore mutated in the same gene. This finding suggests
      that a single step of drug activation operates in sensitive schistosomes and is
      ineffective in resistant worms.

PMID- 8253158
TI  - Entamoeba histolytica: a method for isolate identification.
AB  - The ability to identify individual isolates of Entamoeba histolytica Schaudinn
      1903 (Emend. Walker 1911) is necessary before several important epidemiological
      questions can be answered. We have developed such a method based on our discovery
      of extensive polymorphism in two E. histolytica genes--the serine-rich antigen
      gene and the "strain specific gene"--each of which has an internal tandemly
      repeated structure. Using the polymerase chain reaction we detected both size and
      restriction site polymorphisms in the repetitive regions. When the two genes were
      used in combination we obtained 16 distinct DNA patterns out of 18 isolates
      examined. Moreover, these patterns proved to be stable under a variety of
      conditions--long-term culture, axenization, cell cloning, and animal passage.

PMID- 8253159
TI  - Entamoeba histolytica: an explanation for the reported conversion of
      "nonpathogenic" amebae to the "pathogenic" form.
AB  - The reported conversion of "nonpathogenic" Entamoeba histolytica isolates to the
      "pathogenic" form during attempted axenization of the amebae is highly
      controversial. After failing to obtain conversions ourselves we concluded that
      the simplest explanation for the published observations would be contamination of
      nonpathogenic cultures with pathogenic amebae. To address this possibility we
      used a method based on analysis of stable DNA polymorphisms that allows the
      positive identification of individual pathogenic isolates. The DNA patterns
      obtained using the "converted" amebae proved to be identical to those of
      reference isolates present in the laboratories at the time of conversion. We also
      found that very few cells need be transferred for a pathogenic contaminant to
      become established in a nonpathogenic culture. Cross-contamination fully explains
      the conversion phenomenon and thus recognition of nonpathogenic and pathogenic
      amebae as the distinct species Entamoeba dispar Brumpt 1925 and E. histolytica
      Schaudinn 1903 (Emend. Walker 1911), respectively, is upheld.

PMID- 8253160
TI  - Plasmodium falciparum: a method for the amplification of S antigens and its
      application to laboratory and field samples.
AB  - Polymerase chain reaction amplification of several polymorphic genes has been
      used to study the population biology of Plasmodium falciparum. S antigen is
      particularly suitable for such studies, but difficulties in the amplification of
      this gene have precluded its use. Here we describe a simple method for the
      amplification of S antigen and show why previous attempts may have been
      unsuccessful. Data are presented from both laboratory and field isolates.

PMID- 8253161
TI  - Schistosoma mansoni: fatty acid-induced cercarial tail loss does not involve
      eicosanoid production and chemoreceptors.
AB  - Inhibitors of eicosanoid production had no effect on linoleic acid-induced
      Schistosoma mansoni cercarial tail loss. In addition, linoleic acid-induced
      cercarial tail loss was not inhibited by silver nitrate, which binds to putative
      chemoreceptors for fatty acids in cercariae. There was no correlation between
      molecular structures of fatty acids and their potencies to induce tail loss.
      Furthermore, transcompounds of fatty acids which cannot be precursors of
      eicosanoids elicited tail loss as potently as cis-compounds did. The present
      results suggest that fatty acid-induced cercarial tail loss is not mediated by
      eicosanoid production and chemoreceptors, which are involved in cercarial
      penetration behavior stimulated by fatty acids.

PMID- 8253162
TI  - Ancylostoma caninum: glutathione stimulates feeding in third-stage larvae by a
      sulfhydryl-independent mechanism.
AB  - The reduced form of the tripeptide glutathione has been reported to reinitiate
      feeding by third-stage larvae of the hookworm Ancylostoma caninum. Investigations
      were conducted with the GSH analogue ophthalmic acid to determine the mechanism
      by which GSH stimulates feeding. Ophthalmic acid stimulated feeding, beginning at
      1-2.5 mM and reaching a maximum by 10-15 mM, and also enhanced serum-stimulated
      feeding. The results indicate that GSH stimulates feeding by a specific,
      sulfhydryl-independent mechanism.

PMID- 8253163
TI  - Schistosoma mansoni: induction of protective immunity in rats using a recombinant
      fragment of a parasite surface antigen.

PMID- 8253164
TI  - Schistosoma mansoni: an HSP60 homologue is constitutively expressed in cercariae,
      adults, and sporocysts.

PMID- 8253165
TI  - Acanthocheilonema viteae: phosphorylcholine is attached to the major excretory
      secretory product via an N-linked glycan.

PMID- 8253166
TI  - Pollen.
AB  - This review deals first with basic knowledge about pollen, especially its
      biology, morphology and physiology, and then discusses the connection of pollen
      with medical problems such as hay fever (pollinosis). The next sections cover the
      historical development of methods for trapping and counting airborne pollen
      grains to produce reliable quantitative data, and the development of a European
      network of pollen-reporting stations.

PMID- 8253167
TI  - Pollen flight forecasting in Germany and in Europe.
AB  - Every tenth person in Central Europe is a pollinosis patient. The time of
      ripening and release of pollen, as well as pollen flight, all depend on the
      weather. Because each year is different from every other, mean values from pollen
      calendars do not provide any practical help for allergy-sufferers. For this
      reason, in many European countries, measuring networks have been established
      during the last 10 years as a basis for forecasting the prevalence of airborne
      pollen for the following 2-3 days, in connection with the weather forecast.
      Cooperation and communication also exist on a European level, and a European
      Pollen Database had been established.

PMID- 8253168
TI  - Climatotherapy.
AB  - For successful climatotherapeutic treatment the body has to be exposed daily over
      several weeks under an exact dosage regime, to the biometerological conditions.
      For doing this--to provide rest, or to apply stimuli--four different methods are
      described: climatic terrain treatment, fresh air rest-cures, air baths and
      heliotherapy. Climatotherapy is conducted in a marine climate, in upland and in
      alpine regions. These three zones differ in the intensity of their climatic
      stimuli. Today, climatotherapy has become more differentiated, and has been newly
      structured following objective parameters. It always refers to specific diseases.

PMID- 8253169
TI  - Urban bioclimatology.
AB  - This article deals with the part of urban climatology which is of particular
      relevance to human beings. Presented first is a summary of all human
      biometerologically effective complexes, as well as other factors which are
      relevant to urban planning and which depend on atmospheric conditions in urban
      structures in a direct or indirect manner. Later, methods for human
      biometerologically significant assessment of thermal and air pollution components
      of the urban climate are discussed in detail, because these components can be
      strongly influenced by urban planning. The application of these methods is
      illustrated by some results of appropriate investigations in urban areas.

PMID- 8253170
TI  - Urban bioclimatology in developing countries.
AB  - A brief review of the literature on urban human bioclimatology in the tropics is
      undertaken. Attempts to chart human bioclimatic conditions on the regional/local
      scale have been made in several developing countries. The effective temperature
      scheme (with all its limitations) is the one that has been most frequently
      applied. The possibilities of application of bioclimatic models based on human
      heat balance for the tropical urban environment are discussed.

PMID- 8253171
TI  - The impact of climate change on human health: some international implications.
AB  - The objective of this study is to discuss the potential impact of a global
      warming on various aspects of human health. Changes in heat-related mortality are
      estimated for four countries: the United States, Canada, the People's Republic of
      China and Egypt. In addition, the potential confounding impact of increased air
      pollution is considered. Finally, a framework to analyze two vector-borne
      diseases, onchocerciasis and malaria, which may spread if temperatures increase,
      is discussed. Our findings suggest that heat-related mortality is estimated to
      rise significantly in all four countries if the earth warms, with the greatest
      impacts in China and Egypt. The most sensitive areas are those with intense but
      irregular heat waves. In the United States, air pollution does not appear to
      impact daily mortality significantly when severe weather is present, although it
      seems to have a slight influence when weather conditions are not stressful.

PMID- 8253172
TI  - Growth hormone signal transduction.
AB  - Growth hormone (GH) promotes animal growth by stimulating bone and cartilage cell
      proliferation, and influences carbohydrate and lipid metabolism. Some of these
      effects are brought about indirectly via somatomedin induction in hepatocytes,
      others by acting directly on the target cells. In either case, GH first binds to
      specific receptors on cells to trigger a sequence of biochemical events
      culminating in a biological response. Recently much has been learnt about the
      molecular structure of GH receptor, its binding to ligand, and the ensuing signal
      transduction events.

PMID- 8253174
TI  - Food and nutrition in the management of group feeding programmes. Nutrition
      Programmes Service. FAO Food Policy and Nutrition Division.

PMID- 8253173
TI  - Volume-dependent regulation of the respiratory burst of activated human
      neutrophils.
AB  - The effect of incubation medium osmolality on the respiratory burst of human
      neutrophils was studied using luminol-dependent chemiluminescence (CL) as an
      indicator of burst activity. Neutrophils were stimulated with N-formyl-Met-Leu
      Phe (FMLP), phorbol-12-myristate-13-acetate (PMA), the calcium ionophore A23187,
      thermoaggregated IgG (IgGn), and opsonized zymosan (OZ). It was shown that
      increasing the osmolality of the incubation medium from 320 up to 420 mosM
      decreased the A23187- and OZ-induced CL responses by 90%. Under the same
      conditions PMA-, FMLP- and IgGn-induced CL responses were decreased by 40-60%. A
      decrease of osmolality to 200 mosM resulted in a 2-3 fold decrease of the A23187
      , PMA- and FMLP-induced CL and in a 60-80% increase of OZ- and IgGn-induced CL.
      It is suggested that osmolality-mediated alteration of cell volume is an
      important mechanism for regulating neutrophil activity.

PMID- 8253175
TI  - Ultrasonic evaluation of the lens thickness to axial length factor in primary
      closure angle glaucoma.
AB  - Ultrasonic biometry was done in 232 normal eyes and 138 eyes with primary angle
      closure glaucoma (ACG), using Ultrascan Digital B System IV (10 MHz). The ratio
      between the lens thickness and the axial length (lens thickness to axial length
      factor, LAF) was evaluated as a biometric index for assessing the eye with
      primary ACG in Chinese. LAF of 2.00 was found to be ideal point of demarcation
      between ACG and normal eyes (i.e., lens thickness equals to 1/5 of axial length).
      It appears that LAF is helpful in screening primary ACG eyes from eyes of the
      general population. This is similar to the anterior chamber depth of 2.5 mm which
      is recognized as a threshold for the occurrence of primary angle closure
      glaucoma.

PMID- 8253176
TI  - Election spin resonance studies of free radical formation and oxygen consumption
      of lens epithelium during ultraviolet exposure.
AB  - A long life election spin resonance (ESR) signal at g = 2.0006 was observed in
      the normal lens epithelium and cortical fibers. During ultraviolet (UV) exposure,
      a new ESR signal at g = 2.0060 was found in the lens epithelium. But this
      specific signal was not detected in the lens cortical fibers. This suggested that
      lens epithelial cells were more susceptible to the free radical formation which
      was induced by UV light. By means of ESR spin probe oximetry, the oxygen uptake
      of lens epithelial cells was measured. The more the oxygen uptake, the higher the
      K value was. The K value of the oxygen consumption of epithelial cell linearly
      correlated with time of consumption (20-60 min) and increased as a function of UV
      exposure time (1-5 min). The oxygen consumption rate of lens epithelial cell was
      approximately 1.38 x 10(6) and increased to 7.1 x 10(6) O2 molecules per cell per
      sec. The oxygen consumption rate increased more than 5 times. These results
      indicates that UV light can accelerate the respiratory function of lens
      epithelial cells. The necessity of excess oxygen of lens epithelial cells may
      play a role in the cataract formation induced by UV light.

PMID- 8253177
TI  - Recent advances in IOL surgery.
AB  - Tremendous progress is made in recent time in the field of Ophthalmology
      especially after advent of IOL implantation surgery. Recent advance in
      anaesthesia/IOL, designs/IOL, quotings/cantering, techniques/advances in
      operating microscope and advances in suture materials/needles etc. will be
      discussed.

PMID- 8253178
TI  - Local anesthesia in cataract surgery--a comparison of different methods.
AB  - Seven groups of thirty patients undergoing cataract extraction under local
      anesthesia were each given different combinations of local anesthesia. These
      varied from a maximum approach using supra-orbital, infra-orbital and facial
      blocks with Hyalase, orbital compression and pre-operative Acetazolamide down to
      a minimum group receiving purely an infra-orbital and supra-orbital block with a
      Lignocaine/Bupivacaine mixture. There was no significant difference in local
      analgesia or in the complication rates between the seven groups. The benefits of
      Acetazolamide and orbital compression remain doubtful. The use of Hyalase and of
      a facial block resulted in fewer complications and in better akinesia.

PMID- 8253179
TI  - Development of PVEP in infants and children.
AB  - The development of components of VEP was studied in 150 infants and children
      between 2 weeks and 9 years of age participated as subjects. Ten adult subjects,
      25 to 35 years of age were also studied. The results indicated that the VEP had a
      simple wave form, consisting of only a slowly rising positive wave to 140', 70'
      and 35' checks from infants of 2 to 8 weeks following birth. P1 wave appeared in
      response to 17.5' check stimulus at 10 weeks following birth. The latencies of P1
      components shortened dramatically from infants of 2 to 4 months and the latencies
      of low spatial frequencies (140' and 70' checks) from infants at 4 months of age
      reached adult level but P1 latency of medium spatial frequency (35' check) did
      not reach adult level until age of 4 years. The latency of P1 component of high
      spatial frequency was matured by the end of 9 years of age. The development of P1
      waves from both eyes was parallel in normal infants and children. The amplitudes
      N1P1 and P1N2 from infants and children with 2 months to 9 years were not
      affected by the age and significantly higher than those of adults group by 2 to 3
      factors. Based on the results of our research, three phases were found in the
      development of the visual function in infants and children. The first phase was
      up to 4 months after birth, and characterized by the maturation of the low
      spatial frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253180
TI  - The study of relationships between the damage of visual function and
      hemorrheology, ocular rheography, as well as other related factors in patients
      with primary open angle glaucoma (POAG).
AB  - Researches of glaucoma visual function damage, hemorheology, ocular rheography
      and other related multiplex factors, with computed multifactorial stepwise
      regression analysis, indicate that the elevation of intraocular pressure (IOP) is
      not the only factor to induce visual impairment. POAG patients are shown to have
      markedly reduced diastolic perfusion pressure in ophthalmic artery, besides
      prolonged filling time of the retinal artery and vein, diminished erythrocyte
      deformability and increased platelet adhesion rate. The characteristic of ocular
      rheographic changes in POAG patients of controlled IOP suggest that the abnormal
      changes of hemorheology be responsible for the damage of visual function. The
      abnormal changes of plasma viscosity, blood apparent viscosity, blood
      viscoelasticity, hematocrit, mean red cell volume etc could be found in addition
      to the reduction of PO2, SO2% and trace elements (Cr, Zn, Mg, Fe) in patients
      with POAG. Computed multiply stepwise regression analysis and Bayes
      discrimination were made among the deteriorate rate of quantitative visual field
      and 28 factors from the combined investigation. Only the hemorrheological index
      could be introduced into the multiply regression equations. The more the damage
      of visual function in POAG patients, the more accurate the discriminatory effect.
      Based upon the results, and the reports of articles published as well as the
      search of 1982-1989 Compact Combridge MEDLINE Medical data base, the new clinical
      concept could be presented that POAG might belong to the scope of blood
      hyperviscosity syndromes. When IOP elevation and the decrease of ocular artery
      pressure existed, the damage of visual function in POAG patients should be
      deteriorated.

PMID- 8253181
TI  - The natural history of dry type of age-related macular degeneration.
AB  - To study the natural history of dry type of age-related macular degeneration
      (AMD) and search for a sensitive method for detecting the development of the
      disease, the fundus fluorescein angiography, visual acuity, electroretinogram and
      FM 100-hue test were used to examine 75 eyes, 147 eyes, 73 eyes, and 94 eyes
      respectively. These examinations were taken at least twice during the follow-up
      periods. The average age was 63.2 years (50-80 years). The average follow-up was
      29.8 months with a range of 3-74 months. It was shown tht there were not any
      statistically significant difference in the macular lesions and electroretinogram
      between the initial examinations and after follow-up (P > 0.05). 91.14% of the
      eyes maintained good visual acuity during the follow-up. Subretinal
      neovascularization developed only in one of the eyes. The total error score of FM
      100-hue test had a statistically significant difference between the initial test
      and the test taken two years afterwards (P < 0.01). It was suggested that most of
      the dry type of AMD had a favorable prognosis and that color visual test was a
      sensitive method for monitoring the development of dry type of AMD.

PMID- 8253182
TI  - Detection of tumor suppressor gene and oncogene in So-Rb50 human retinoblastoma
      cell line.
AB  - Retinoblastoma (Rb) is the most common malignant cancer of eye. So-Rb50 is the
      first Rb cell line established in China in 1988. It has passed to the 387th
      passage now. We collected cells of the 327th passage of SO-Rb50, purified its
      genomic DNA and detected it with Rb and c-myc cDNA probes respectively (normal
      human white blood cells DNA was the control). We found the Rb gene was deleted
      while c-myc gene was amplified three times. This provides a basis for further
      study of the regulation of tumor development and tumor reversal with this cell
      line in vitro.

PMID- 8253183
TI  - Dynamic investigation on chromosome aberration of a human retinoblastoma cell
      line So-Rb50.
AB  - G-banding and karyotype analyses of cells in seventeen passages of SO-Rb50 during
      a long period of culture for about four years were performed. Three chromosome
      markers 13q14-, 1p36+ and 12p13+ were found. Cells possessed 13q14- reduced to
      zero after the 200th passage while 1p+ and 12p+ cells increased to 100% after 30
      and 200 passages respectively. Abnormal chromosomes, ring chromosomes, chromosome
      radiuses and double minutes were also observed. These chromosomal changes were
      more often seen before the 200th passage. The significance of these changes are
      discussed.

PMID- 8253184
TI  - Updates in orbital tumors.
AB  - Orbital anatomy, the clinical features of orbital tumors, the recent development
      of the diagnosis and management of orbital tumors were described. The incidence
      of orbital tumors in Dr. Cipto Mangunkusumo Hospital in the past years were
      introduced. The principle of management of orbital tumors and their prognosis
      were discussed.

PMID- 8253185
TI  - A fundus photographic method with narrow spectral band luminance.
AB  - We perfected the narrow spectral band fundus photographic system using
      interference filters at the wavelengths of 417, 478, 500, 530, 547, 570, 589,
      607, 628 and 648 nm. Tests about the light penetration of filters and exposure of
      various brand films were made on this system. Studies of the contrast of fundal
      tissues and structures under the different narrow spectral band light were made
      on 43 Chinese fellow eyes. The results indicates that the interference filters of
      570 nm have the highest light penetration. Kodak and Gongyuan films (make in
      China) are the optimal ones. Narrow spectral band fundus photography can
      eliminate the chromatic aberration and therefore improve the documentation of
      fundal details, enhance the contrast of pictures as compared with routine white
      light fundus photography.

PMID- 8253186
TI  - Autocatalytic modification of human carbonyl reductase by 2-oxocarboxylic acids.
AB  - Carbonyl reductase occurs in multiple molecular forms. Sequence analysis has
      yielded a carboxyethyllysine residue in one of the enzyme forms, suggesting that
      pyruvate has been incorporated in a posttranslational enzymatic reaction [Krook,
      M., Ghosh, D., Stromberg R., Carlquist, M. and Jornvall, H. (1993) Proc. Natl.
      Acad. Sci. USA 90, 502-506]. Using highly purified carbonyl reductase from human
      brain we show that pyruvate and other 2-oxocarboxylic acids are bound to the
      enzyme in an autocatalytic reaction. The resulting enzyme forms were
      indistinguishable from the native enzyme forms by electrophoresis and isoelectric
      focusing.

PMID- 8253187
TI  - The Drosophila ankyrin repeat protein cactus has a predominantly alpha-helical
      secondary structure.
AB  - The cactus protein is the Drosophila homologue of the mammalian I kappa B family
      of cytoplasmic anchor proteins. We have expressed in E. coli and purified a
      cactus fusion protein, CACT-Bgl. CACT-Bgl protein contains the six ankyrin repeat
      sequences which are necessary for specific binding to the Drosophila rel family
      transcription factor dorsal. We show that the purified CACT-Bgl protein can bind
      specifically to dorsal and, using circular dichroism spectroscopy, that the
      protein adopts a largely alpha-helical secondary structure. A further analysis of
      the ankyrin repeat domains of cactus, using an improved secondary structure
      prediction program indicates that the N-terminal of the repeat will form into a
      loop structure and the C-terminal section into an interrupted, amphipathic alpha
      helix. On the basis of these findings we propose that the ankyrin repeats of
      cactus fold together into helical bundles interconnected by diverged loops.

PMID- 8253188
TI  - The growth-supportive effect of thrombospondin (TSP1) and the expression of TSP1
      by human MG-63 osteoblastic cells are both inhibited by dexamethasone.
AB  - Thrombospondin (TSP) is a 450-kDa extracellular matrix glycoprotein which
      supports the growth of human MG-63 osteoblastic cells [Abbadia et al., FEBS
      Lett., 329 (1993) 341-346]. In this study, we describe the effect of the
      glucocorticoid, dexamethasone, on cell proliferation and TSP expression by MG-63
      cells. Using a serum-free mitogenesis assay, dexamethasone (25 to 500 nM) caused
      a dose-dependent decrease in [3H]thymidine incorporation by MG-63 cells in
      culture, reaching 40% inhibition of cell proliferation at a concentration of 250
      nM. Similarly, the stimulatory effect of TSP (500 ng/ml) on proliferation of MG
      63 cells was totally abolished in the presence of dexamethasone (250 nM). In situ
      hybridization indicated that TSP mRNA level in dexamethasone-treated MG-63 cells
      decreased compared to quiescent cells. As judged by fluorescence-activated cell
      sorting analysis, dexamethasone treatment of MG-63 cells resulted in a 50 to 70%
      decrease in TSP cell surface expression compared to quiescent cells. Secretion of
      TSP in the culture fluid of dexamethasone-treated MG-63 cells also decreased by
      40% while, under similar experimental conditions, a 180% increase in alkaline
      phosphatase activity was observed in dexamethasone-treated cells. Because
      glucocorticoids induce osteoporosis in vivo and reduce proliferation of
      osteoblasts in vitro, our results argue for an important role of TSP during bone
      formation.

PMID- 8253189
TI  - The first application of a chemiluminescence probe, 2-methyl-6-[p-methoxyphenyl]
      3,7-dihydroimidazo[1,2-a]pyrazin-3-one (MCLA), for detecting O2- production, in
      vitro, from Kupffer cells stimulated by phorbol myristate acetate.
AB  - The purpose of this study was to investigate the generation of superoxide anion
      radical, O2-, by Kupffer cells in vivo in rat liver. Phorbol myristate acetate
      (PMA) was infused into perfused rat liver which had been continuously infused
      with 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo- [1,2-a]pyrazin-3-one (MCLA,
      a highly sensitive luminescence reagent for O2-) and the MCLA luminescence from
      the liver surface was detected with a sensitive photon counter. Under identical
      conditions, but without MCLA infusion, PMA and nitro blue tetrazolium were
      infused to verify generation of O2- by formation of formazan deposition. Based on
      MCLA luminescence and formazan deposition, both dependent on the O2- reaction, we
      have concluded that liver Kupffer cells generate O2- in vivo in response to
      stimuli such as PMA. Further, the generation of O2- by Kupffer cells may be by
      the same mechanism as displayed by macrophages.

PMID- 8253190
TI  - A cdc2-related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau
      protein kinase II, a proline-directed protein kinase associated with microtubule.
AB  - We previously reported that tau protein kinase II (TPKII) from bovine brain was
      composed of 30 kDa and 23 kDa subunits. The 30 kDa subunit of TPKII can be
      regarded as a catalytic subunit because of its ATP-binding activity. Antibodies
      directed against TPKII-phosphorylated tau also reacted with tau phosphorylated by
      cdc2 kinase obtained from starfish oocytes, indicating that TPKII and cdc2 kinase
      phosphorylate the same sites. We determined the amino acid sequence of the 30 kDa
      subunit and found it to be homologous with a cdc2-related kinase, PSSALRE/cdk5.
      Moreover, an antibody against PSSALRE/cdk5 reacted with the 30 kDa subunit. These
      results indicate that the 30 kDa subunit of TPKII is bovine homologue of
      PSSALRE/cdk5. Expression of the 30 kDa subunit mRNA was enhanced in juvenile rat
      brain. This result supports our previous hypothesis that the kinase works
      actively in juvenile brain.

PMID- 8253191
TI  - Biochemical characterization of a 34 kDa ribonucleoprotein (p34) purified from
      the spinach chloroplast fraction as an effective phosphate acceptor for casein
      kinase II.
AB  - A 34 kDa ribonucleoprotein (p34) was purified to homogeneity from a 1.0 M KCl
      extract of spinach chloroplasts and characterized as an effective phosphate
      acceptor for casein kinase II (CK-II). The N-terminal 21 residues (W-V-A-Q-T-S-E
      E-E-Q-E-G-S-T-N-A-V-L-E-G-E) of p34 were 95% identical with the sequence reported
      for 28RNP (plastid mRNA 3' end processing factor in chloroplast). Moreover, the
      findings that DNAs as well as RNAs significantly stimulate the CK-II catalyzed
      phosphorylation of p34 in vitro and induce its conformational change, suggest
      that the physiological activity of p34-bound RNA or DNA in chloroplast post
      transcriptional regulation is controlled by specific p34 phosphorylation by CK
      II.

PMID- 8253192
TI  - Compositional compartmentalization of the nuclear genomes of Trypanosoma brucei
      and Trypanosoma equiperdum.
AB  - High molecular weight DNA preparations from Trypanosoma brucei and Trypanosoma
      equiperdum were fractionated by preparative centrifugation in a Cs2SO4 density
      gradient in the presence of BAMD, bis(acetatomercurimethyl)dioxane, a sequence
      specific DNA ligand. Analytical centrifugation in CsCl of the DNA fractions so
      obtained showed that both DNAs had a bimodal distribution with two major peaks
      banding at 1.702-1.703 and 1.708 g/cm3 and representing 1/3 and 2/3 of total DNA,
      respectively. Several minor components were also detected. These results indicate
      that a compositional compartmentalization is not only found in the genome of
      vertebrates and plants, as already described, but also in those of protozoa such
      as Trypanosomes.

PMID- 8253193
TI  - Suppression of neuronal potassium A-current by arachidonic acid.
AB  - The effect of arachidonic acid on the A current (IA) has been studied in
      dissociated bullfrog neurons under whole-cell voltage-clamp conditions.
      Arachidonic acid reduced IA in a dose-dependent and reversible manner without a
      shift in the prepulse inactivation voltage-current relation. 1.75 microM
      inhibited IA by 50%, and higher concentrations caused a total suppression. In
      addition, arachidonic acid increased the M-current (IM), a different potassium
      current that does not inactivate. Neither indomethacin nor nordihydroguaiaretic
      acid, cyclooxygenase and lipoxygenase inhibitors respectively, prevented IA
      reduction. In contrast, nordihydroguaiaretic acid prevented IM enhancement.
      Eicosatetraynoic acid, an arachidonic acid analog that cannot be metabolized,
      also reduced IA. These results suggest that arachidonic acid metabolism is not
      required to suppress IA.

PMID- 8253194
TI  - Characterization of two cDNAs (ERD11 and ERD13) for dehydration-inducible genes
      that encode putative glutathione S-transferases in Arabidopsis thaliana L.
AB  - Two cDNA clones, designated ERD11 and ERD13, isolated from a cDNA library from
      Arabidopsis thaliana L. plants dehydrated for 1 h were sequenced and
      characterized. These clones encoded polypeptides that were homologous to
      glutathione S-transferases of tobacco and maize. Genomic Southern hybridization
      suggested that there are a few additional genes showing high similarity to the
      ERD11 gene in the Arabidopsis genome. The expression of the genes for ERD11 and
      ERD13 was induced by dehydration, but was not affected by the application of four
      plant growth regulators, 2,4-dichlorophenoxyacetic acid 6-benzylaminopurine,
      abscisic acid, or gibberellic acid.

PMID- 8253195
TI  - Effect of 67 kDa calcimedin on caldesmon functioning.
AB  - Interaction of smooth muscle caldesmon with calmodulin, troponin C, S-100 protein
      and 67 kDa calcimedin was analyzed. Native gel electrophoresis and crosslinking
      revealed the complex formation between caldesmon and three EF-hand Ca-binding
      proteins, whereas calcimedin did not interact with caldesmon. In the presence of
      Ca2+, calcimedin binds to actin-tropomyosin without affecting the interaction of
      caldesmon with this complex. Although calcimedin reversed the inhibitory action
      of caldesmon on the actomyosin ATPase activity at a lower concentration than
      three other Ca-binding proteins, this effect only slightly depends on Ca2+ and
      was observed at the concentration of calcimedin comparable to that of actin. It
      is concluded that calcimedin itself cannot be responsible for Ca-dependent
      regulation of caldesmon functioning, but actin bundling induced by calcimedin (or
      by other actin binding proteins) decreases the inhibitory action of caldesmon on
      the actomyosin ATPase activity.

PMID- 8253196
TI  - Nucleoside triphosphatase activity associated with the N-terminal domain of
      mammalian tryptophanyl-tRNA synthetase.
AB  - Bovine tryptophanyl-tRNA synthetase (EC 6.1.1.2) deprived of Zn2+ by chelation
      with the phosphonate analog of Ap4A hydrolyzed ATP(GTP) to ADP(GDP) although its
      ability to form tryptophanyl adenylate was impaired. This hydrolytic activity is
      stimulated by Mg2+ and Mn2+ ions and inhibited by Zn2+. Monoclonal antibody Am1
      against the N-terminal domain of the enzyme completely abolished ATP(GTP)ase
      activity. The core peptide generated after proteolytic splitting of the N-domain
      lacks this activity. We suggest that the nucleotide binding site(s) different
      from ATP sites involved in aminoacylation reaction reside(s) at the N-terminal
      domain(s) of the enzyme.

PMID- 8253197
TI  - High-affinity binding of a protein-lipopolysaccharide phytotoxin from
      Verticillium dahliae to cotton membranes.
AB  - The presence of a specific binding site for a protein-lipopolysaccharide (PLP)
      phytotoxin isolated from culture filtrates of Verticillium dahliae has been
      demonstrated in plasma membranes from cotton seedlings. The 125I-labelled PLP was
      used as a ligand in binding assays with plasma membrane enriched fractions. Root
      tissue exhibited the highest amount of binding activity compared to hypocotyl and
      cotyledon tissue. Binding of the [125I]PLP was saturable, reversible, and with an
      affinity (Kd = 1.42 x 10(-8) M) comparable with the concentration required for
      biological activity. A single class of binding site was found, and the maximal
      number of binding sites were estimated as 5.4 x 10(-15) mol/micrograms protein.

PMID- 8253198
TI  - Different ratios in 20 S proteasomes and regulatory subunit complexes in two
      isoforms of the 26 S proteasome purified from rabbit skeletal muscle.
AB  - A ubiquitin/ATP-dependent proteinase complex (26 S proteasome) was highly
      purified from rabbit skeletal muscle. The purified 26 S proteasome easily
      dissociated into a 20 S proteasome and a regulatory subunit complex on non
      denaturing PAGE. By using cleavable and non-cleavable cross-linkers, it was
      revealed that the 26 S proteasome exists in two isoforms: one (D complex)
      consists of the 20 S proteasome and the regulatory subunit complex in the ratio
      of one to two, while the other (C complex) exists in an equal molar ratio.
      Molecular masses of the former and the latter isoforms were estimated to be 1,700
      kDa and 1,400 kDa, respectively, by gel filtration, and 2,400 kDa and 1,400 kDa,
      respectively, by Ferguson plot analysis. Furthermore, both isoforms efficiently
      hydrolyzed Suc-Leu-Leu-Val-Tyr-MCA and ubiquitin-conjugated [125I]lysozyme. These
      results suggest that the D and C complexes are active proteinase complexes, most
      probably corresponding to the dumbbell-like and mushroom-like (or space capsule
      like) molecules, respectively.

PMID- 8253199
TI  - Caldecrin proform requires trypsin activation for the acquisition of serum
      calcium-decreasing activity.
AB  - Proform serum calcium-decreasing factor (procaldecrin) was purified from porcine
      pancreas acetone powder. Procaldecrin showed chymotrypsin activity after trypsin
      treatment in a time- and dose-dependent manner. Procaldecrin did not possess
      serum calcium-decreasing activity but acquired serum calcium-decreasing activity
      as well as protease activity after trypsin treatment. However, PMSF treatment
      after activation of procaldecrin by trypsin did not affect the serum calcium
      decreasing activity, even though protease activity was nullified by treatment
      with PMSF. These findings suggest that the serum calcium-decreasing activity
      acquired by procaldecrin requires conformational change caused by trypsin
      treatment.

PMID- 8253200
TI  - Phosphorylation of the L-type calcium channel beta subunit is involved in beta
      adrenergic signal transduction in canine myocardium.
AB  - Cyclic AMP-mediated phosphorylation of calcium channel subunits was studied in
      vitro and in vivo in preparations from dog heart. Calcium channels in native
      cardiac membranes were phosphorylated by cAMP-dependent protein kinase (PKA)
      solubilized with digitonin and subsequently immunoprecipitated using a polyclonal
      antibody generated against the deduced carboxy-terminal sequence of the cardiac
      beta subunit. A 62 kDa protein was identified as the major PKA-substrate in the
      immunoprecipitates. In the intact myocardium, this putative beta subunit was
      found to be phosphorylated in response to cAMP elevating agents. In contrast, no
      phosphorylation of a protein with an electrophoretic mobility similar to the
      alpha 1 subunit was detected, although 1,4-dihydropyridine receptor sites were
      recovered in the immunoprecipitates. Thus, we suggest that PKA-mediated
      phosphorylation of the beta subunit is the major mechanism for beta-adrenergic
      regulation of cardiac L-type calcium channel activity.

PMID- 8253201
TI  - Detection of Duchenne muscular dystrophy gene products in amniotic fluid and
      chorionic villus sampling cells.
AB  - We have examined the expression of several Duchenne muscular dystrophy (DMD) gene
      products in amniotic fluid (AF) and chorionic villus sampling (CVS) cells.
      Variable amounts of dystrophin could be detected in most CVS and AF samples by
      immunoprecipitation followed by Western blot analysis. PCR analysis demonstrated
      the presence of the muscle type dystrophin mRNA in all AF cell cultures. The
      brain type dystrophin mRNA was also detected in some of these cultures. These DMD
      gene transcripts are of fetal origin and are produced by most or all clonable AF
      cells. The results may facilitate the development of a method for prenatal
      diagnosis of DMD, based on the expression of the gene in AF and CVS cells.

PMID- 8253202
TI  - Human lymphocyte antigen CD38 catalyzes the production of cyclic ADP-ribose.
AB  - The human lymphocyte antigen CD38 has been shown to share sequence homology with
      ADP-ribosyl cyclase, the enzyme that catalyzes the conversion of NAD+ to cyclic
      ADP-ribose (cADPR), a potent Ca(2+)-mobilizing agent. In this study COS1 cells
      from African Green Monkey kidney were transiently transfected with CD38 cDNA,
      inducing expression of authentic CD38 on the cell surface. We demonstrate that
      CD38 expressed in this manner can convert NAD+ to cADPR in the extracellular
      medium as assessed by Ca2+ release from sea-urchin egg microsomes.

PMID- 8253203
TI  - In vivo biosynthesis of cholesterol in the rat retina.
AB  - Previous reports have suggested that the rate of de novo cholesterol synthesis in
      the adult vertebrate retina is extremely slow. We investigated cholesterol
      biosynthesis in the adult rat retina in vivo, following intravitreal injection of
      [3H]acetate. HPLC analysis of retinal non-saponifiable lipid extracts revealed co
      elution of radioactivity with endogenous cholesterol mass within 4.5 h post
      injection. Incorporation of [3H]acetate into cholesterol was markedly reduced by
      co-injection of known inhibitors of the cholesterol pathway. In contrast to
      previous results with retinas from other species, no radiolabel or mass
      corresponded to squalene, except in lipid extracts from retinas treated with NB
      598, a squalene epoxidase inhibitor. These results demonstrate, for the first
      time, the capacity of the adult vertebrate retina to rapidly synthesize
      cholesterol de novo.

PMID- 8253204
TI  - Electrophoretically defined myosin heavy chain patterns of single human muscle
      spindles.
AB  - At least four myosin heavy chain (MHC) isoforms were separated by SDS-PAGE in
      extracts of intrafusal fibers isolated by microdissection from human lumbrical
      muscles. The fastest migrating MHC represents a slow isoform. The slowest
      migrating MHC was identified as the embryonic MHCemb. A faint band, moving
      slightly faster than MHCemb, most likely represents a neonatal/fetal MHC isoform.
      A prominent band, moving between the latter and the slow isoform is suggested to
      represent a hitherto unidentified, spindle-specific MHC isoform, MHCif.

PMID- 8253205
TI  - Electrophoretic analysis of myosin heavy chain isoform patterns in extraocular
      muscles of the rat.
AB  - Six oculorotatory muscles and the levator palpebrae muscle of the rat were
      analysed by SDS-PAGE for their myosin heavy chain (MHC) isoform patterns.
      Oculorotatory muscles display a marked predominance of fast MHC isoforms. They
      contain, in addition to the slow (MHCI) and fast (MHCIIb, MHCIId, MHCIIa)
      skeletal MHCs, the neonatal MHCneo and the extraocular MHCeom. The levator
      palpebrae, generally assumed to be a member of the extraocular muscle group
      because of its innervation by the oculomotor nerve, does not contain MHCneo and
      MHCeom. It resembles a fast-twitch skeletal muscle with a predominance of MHCIId.

PMID- 8253206
TI  - Purification of hydroxylamine oxidase from Thiosphaera pantotropha.
      Identification of electron acceptors that couple heterotrophic nitrification to
      aerobic denitrification.
AB  - Thiosphaera pantotropha, a Gram-negative heterotrophic nitrifying bacterium,
      expresses a soluble 20 kDa monomeric periplasmic hydroxylamine oxidase that
      differs markedly from the hydroxylamine oxidase found in autotrophic bacteria.
      This enzyme can use the periplasmic redox proteins, cytochrome c551 and
      pseudoazurin as electron acceptors, both of which can also donate electrons to
      denitrification enzymes. A model of electron transfer is proposed, that suggests
      a coupling of nitrification and provides a mechanism by which nitrification can
      play a role in dissipating reductant.

PMID- 8253207
TI  - Different factors bind to the regulatory region of the Na+,K(+)-ATPase alpha 1
      subunit gene during the cell cycle.
AB  - Three factors that bind to the positive regulatory region (ARE) of the Na+,K(+)
      ATPase alpha 1-subunit gene were shown to be present in growing BALB/c-3T3 cells
      as shown by the gel retardation assay pattern in which three specific complexes
      (C1, C2 and C3) were identified. The complexes are similar to those observed in
      MDCK cell nuclear extracts in which linker substitution mutations in the
      competitor gave parallel specific effects in both cells. During the process of
      the cell growth cycle, the relative mobility of C3 was altered, and the amount of
      C1 decreased in the G0 state. All three complexes (C1, C2 and C3) disappeared and
      other specific complexes with higher mobilities were alternatively observed at 6
      h after serum stimulation and thereafter. The expression of the mRNA for the
      alpha 1-subunit gene was repressed at G0 and gradually increased after serum
      stimulation. These results suggest that different sets of factors are responsible
      for the transcription of the gene at different stages of the cell cycle.

PMID- 8253208
TI  - Characterisation of a novel cysteine/histidine-rich metal binding domain from
      Xenopus nuclear factor XNF7.
AB  - A 42 amino acid synthetic peptide corresponding to a newly defined
      cysteine/histidine-rich protein motif called B-box, from the Xenopus protein XNF7
      has been characterised. The metal-binding stoichiometry and dissociation constant
      for zinc were determined by competition with the chromophoric chelator Br2BAPTA,
      demonstrating that one zinc atom binds per molecule of peptide despite the
      presence of seven putative metal ligands, and represents the first application of
      this method to measuring zinc stoichiometry of proteins and/or peptides. Cobalt
      binding studies indicate that the motif binds zinc more tightly than cobalt, that
      cysteines are used as ligands and that the cation is co-ordinated tetrahedrally.
      Circular dichroism and NMR studies both indicate that the B-box peptide is
      structured only in the presence of zinc, copper and to a lesser extent cobalt.

PMID- 8253209
TI  - High sensitivity to site directed mutagenesis of the peptide segment connecting
      phosphorylation and Ca2+ binding domains in the Ca2+ transport ATPase.
AB  - Nine residues (Leu321, Lys329, Asn330, Val333, Arg334, Leu336, Pro337, Val339 and
      Glu340), within the peptide segment intervening between the catalytic domain and
      the Ca2+ binding domain of the sarcoplasmic reticulum (SERCA 1) ATPase, were
      individually mutated to Ala. The mutated proteins were recovered in the
      microsomal fraction of COS-1 cells following transient expression, and exhibited
      inhibition of Ca2+ uptake and ATPase hydrolytic activity, while forming
      discernable levels of phosphorylated intermediate. Mutation of Glu340 to Gln
      (rather than to Ala) was much less effective, suggesting that the functional
      consequence of the mutation is related to structural perturbation, rather than
      loss of the acidic side chain. The high sensitivity of this peptide segment to
      single mutations suggests that its structural integrity is required for
      functional linkage of the phosphorylation and Ca2+ binding domains.

PMID- 8253210
TI  - The role of apoptotic and necrotic processes in cytolysis mediated by LAK cells
      with different phenotypes.
AB  - The role of necrotic and apoptotic pathways in cytolysis mediated by LAK cells
      was studied. The contribution of necrotic and apoptotic processes to cytolysis
      depends both on the LAK cells' phenotype and the type of target cells.
      CD16+/CD8+/CD3- LAK cells induced necrosis of K562 and L929 target cells. The
      cell death induced by CD3+/CD8+/CD16- LAK cells was found to include features of
      apoptotic and necrotic processes.

PMID- 8253211
TI  - Internal ribosome entry site of encephalomyocarditis virus RNA is unable to
      direct translation in Saccharomyces cerevisiae.
AB  - To evaluate the potential of the encephalomyocarditis virus (EMCV) internal
      ribosome entry site (IRES) to promote efficient expression of foreign genes in
      the yeast, S. cerevisiae, we have constructed E. coli-yeast shuttle vectors in
      which the EMCV 5' non-coding region was fused to the reporter gene, human
      prothymosin alpha. Efficiency of translation of corresponding RNA transcripts in
      mammalian cell-free systems was highly dependent on the sequence context and/or
      position of the initiation codon. No translation of these IRES-dependent mRNAs
      occurred in S. cerevisiae.

PMID- 8253212
TI  - A novel beta-N-acetylglucosaminidase activity in hog gastric mucosal microsomes:
      preferential hydrolysis of terminal GlcNAc beta 1-3 linkages in GlcNAc beta 1
      3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc, but GlcNAc beta 1-6 linkages in GlcNAc beta
      1-3(GlcNAc beta 1-6)Gal.
AB  - Hog gastric mucosal microsomes contain beta-N-acetylglucosaminidase activity
      which cleaves GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4GlcNAc at the terminal
      GlcNAc beta 1-3Gal linkage faster than at the GlcNAc beta 1-6Gal bond, producing
      mainly GlcNAc beta 1-6Gal beta 1-4GlcNAc. In a marked contrast, GlcNAc beta 1
      3(GlcNAc beta 1-6)Gal is cleaved primarily at the GlcNAc beta 1-6Gal bond, while
      partial hydrolysis of GlcNAc beta 1-3(GlcNAc beta 1-6)Gal beta 1-4Glc reveals
      similar rates of cleavage for the (1-3) and (1-6) linkages. Our data support the
      notion that the terminal beta 1,6-linked GlcNAc unit of GlcNAc beta 1-3(GlcNAc
      beta 1-6)Gal beta 1-4GlcNAc may interact with the reducing end GlcNAc unit
      intramolecularly in water solution.

PMID- 8253213
TI  - Effect of catalytically active recruited crystallins on lens metabolism.
AB  - The impact on duck lens metabolism of recruited epsilon-crystallin/LDH-B4 and tau
      crystallin/enolase was investigated by NMR spectroscopy. A comparison of the duck
      lens metabolite profile with that of the calf in which recruited crystallins are
      absent revealed significant increases in ATP, alpha-glycerophosphate (alpha-GP)
      and pyridine dinucleotide concentrations. The alterations in the concentrations
      of ATP and alpha-GP appear to be related to both the high concentration of NAD
      and the elevated reduced to oxidized NADH/NAD+ ratio.

PMID- 8253214
TI  - Evolutionary clustering and functional similarity of RNA-binding proteins.
AB  - RNA-binding proteins (RNPs) involved in splicing, processing and translation
      regulation contain one to four RNA-binding domains. We constructed a phylogenetic
      tree for the RNA-binding domains, including those of poly(A)-binding protein
      (PABP), splicing factors, chloroplast RNPs, hnRNPs, snRNP U1-70K, nucleolin and
      Drosophila sex determinants. Proteins with similar functions were found to have
      closely related RNA-binding domains and common domain organizations. In light of
      these observation, one can assume the function of an RNA-binding protein, based
      on the evolutionary relationship between its RNA-binding domain(s) and domain
      organization, as compared with other RNPs.

PMID- 8253215
TI  - The similarity of cytochrome c and ubiquinol oxidases.

PMID- 8253216
TI  - Further comparison of ubiquinol and cytochrome c terminal oxidases.

PMID- 8253217
TI  - Introduction to adenoviruses: an overview of morphology, classification and
      epidemiology.

PMID- 8253218
TI  - The role of a rapid diagnostic test (adenovirus immune dot-blot) in the control
      of an outbreak of adenovirus type 8 keratoconjunctivitis.
AB  - Twenty-three patients were involved in an outbreak of adenovirus type 8 infection
      based at the Manchester Royal Eye Hospital in the spring of 1991. Confirmation of
      adenovirus infection was by means of the immune dot-blot test (IDBT) and virus
      culture, the latter, allowing serotype 8 to be identified as the cause.
      Epidemiological tracing and limited restriction endonuclease analysis of the
      virus isolated suggest that 15 patients contracted the infection within the
      Casualty Department following attendance for minor eye trauma, 10 being infected
      by the same junior doctor. Seven patients presented with an established
      adenovirus type 8 conjunctivitis at the first hospital visit and the source of
      their infection could not be identified. Laboratory confirmation of adenoviral
      involvement took an average of 5 days by IDBT, compared with 33 days by virus
      culture. Rapid identification of adenovirus by IDBT enabled early institution of
      control measures thereby limiting the size of the outbreak.

PMID- 8253219
TI  - Antiviral agents for ocular adenovirus infections.
AB  - Despite significant knowledge of the molecular biology and genetics of
      adenovirus, no specific antiviral agent has been developed for use in adenovirus
      infections. This contrasts with the situation in herpes simplex virus (HSV) and
      human immunodeficiency virus (HIV) infections, in which antiviral agents target
      specific enzymes. Antiviral agents active against HSV and interferons have been
      used in the treatment of ocular adenovirus infections with limited effect. Some
      newer nucleoside analogues have inhibitory activity against adenovirus in vitro
      and their effect is being assessed in newly developed animal models. Live
      vaccines have been used in both the United States and Canada to protect military
      recruits against adenovirus-induced respiratory disease. However, the inoculating
      strains are not normally associated with epidemic keratoconjunctivitis (EKC).
      There is a low prevalence of antibody against strains of adenovirus inducing EKC.
      Until such time as specific antiviral agents against adenovirus are developed,
      the mainstays of therapy will remain topical antibiotics to eliminate any
      secondary bacterial infection and topical steroids to suppress the immune
      response against adenovirus or adenovirus-infected cells. Neither form of
      treatment is adenovirus specific.

PMID- 8253220
TI  - The origin of keratopathy in chronic allergic eye disease: a histopathological
      study.
AB  - Although the clinical features of atopic keratoconjunctivitis have been well
      described, it is recognised that some adults with severe chronic allergic
      conjunctivitis do not develop a keratopathy despite having marked disease of
      their lid margins and conjunctiva. The aetiology of the keratopathy of chronic
      allergic eye disease is not known but may result from the release of toxic
      mediators from mast cells, eosinophils and neutrophils in the inflamed
      conjunctiva. To examine this theory we have counted these cells in tarsal and
      bulbar conjunctival biopsies from patients with severe allergic conjunctivitis
      and compared the numbers in samples from patients with or without keratopathy.
      Our results indicate that patients with chronic allergic conjunctivitis with
      keratopathy have higher cell numbers in their conjunctiva than patients with no
      keratopathy, especially those staining for eosinophil cationic protein in the
      tarsal epithelium. A statistically significant difference between disease groups
      could only be demonstrated, however, when the combined totals of mast cells,
      eosinophils and neutrophils were compared.

PMID- 8253221
TI  - The immunopharmacological actions of nedocromil sodium relative to the use of its
      2% ophthalmic solution.
AB  - The immunopharmacological actions of nedocromil sodium are fully compatible with
      administration to man. Nedocromil sodium exhibits a wide range of anti
      inflammatory actions. When compared with sodium cromoglycate, nedocromil sodium
      is more potent and a major difference is seen in the Ascaris-sensitised monkey
      subjected to bronchial challenge with specific antigen. In this model of chronic
      airway disease nedocromil sodium provides significant protection against changes
      in airway resistance and lung compliance provoked by antigen challenge. Sodium
      cromoglycate does not. This difference is most readily explicable by the greatly
      enhanced effect of nedocromil sodium, relative to that of sodium cromoglycate, in
      preventing the release of mediators such as histamine, leukotriene C4 and
      prostaglandin D2 from the cellular population of the chronically inflamed
      bronchus, especially from mast cells of the mucosal type. There is growing
      evidence that these mediators are important in allergic diseases of the eye and
      this additional activity may be expected to give nedocromil sodium extended scope
      in the management of conjunctivitis in which allergic inflammation and
      hyperresponsiveness are significant pathophysiological factors.

PMID- 8253222
TI  - Nedocromil sodium in contact-lens-associated papillary conjunctivitis.
AB  - Forty-five patients with contact-lens-associated papillary conjunctivitis (CLAPC)
      were included in a 6-week double-masked group comparative study of unpreserved 2%
      nedocromil sodium eye drops and placebo. Data were collected by diary card
      recording of symptoms and duration of lens wear, assessment of symptoms at clinic
      visits, biomicroscopic appraisal of signs on the globe and the upper tarsal
      conjunctiva, and laboratory analysis of tear and serum IgE levels. All
      assessments were made by the same clinician throughout the study. Diary card
      records demonstrated that there was significantly less itching in the nedocromil
      sodium group compared with the placebo group during weeks 1-3 of the study (p <
      0.01), but not during weeks 4-6. Findings for duration of lens wear were
      inconclusive, due to differences between the groups at admission. Biomicroscopic
      assessment showed a significant difference in mucus found on the upper tarsal
      surface in favour of nedocromil sodium by the end of the study (p < 0.02). Twenty
      one patients experienced adverse events during the study. The most common were
      taste and/or stinging on insertion of the drops. No significant difference was
      seen for tear or serum IgE between the two treatment groups during the study.

PMID- 8253223
TI  - Adenovirus keratoconjunctivitis: an enigma.
AB  - 'Adenovirus keratoconjunctivitis' is a diagnosis commonly made in Eye Casualty
      Departments. There are no clinical features that allow identification of the
      serotype causing the infection. The changeable patterns of presentation and
      manifestation of the different serotypes and the capacity of adenovirus to mimic
      other viral or bacterial infections is an enigma. Adenovirus infections are
      usually self-limiting; permanent visual loss is very rare. The use of
      corticosteroids is generally limited to cases with severe symptoms such as glare
      and incapacitating blurring of vision. Corticosteroids will not alter the basic
      pathogenesis of the disease but will suppress inflammatory signs. The sub
      epithelial lesions are an immunopathological phenomenon resulting from the
      interaction of viral antigen and antibody in the anterior stroma with the cornea
      acting as a 'blotter'. An effective antiviral remains elusive.

PMID- 8253224
TI  - Molecular epidemiology of adenovirus conjunctivitis in Glasgow 1981-1991.
AB  - Adenoviruses isolated over a period of 10 years from patients with conjunctivitis
      were typed by neutralisation test using reference sera and by restriction
      endonuclease fragment (REF) analysis. Adenoviruses were isolated from 516 of
      10,232 patients tested (5.0%); 154 were identified as type 3, 153 as type 4, 70
      as type 7, 17 as type 10 and 122 as other types. At any one time, several
      serotypes co-circulated. The prevalence of types varied. Type 4 was not isolated
      in the first 2 years and then gradually increased in incidence, becoming the most
      frequently isolated type after 1987. Two periods of increased isolation frequency
      occurred: firstly from May to August 1981, when 8-28% of patients per month were
      found to be adenovirus-positive, with serotype 3 being predominant; and secondly
      from January 1989 to August 1990, when 8-20% of patients per month were
      adenovirus-positive, predominantly with type 4. Analysis of REFs showed that
      several different genotypes exist within serotypes. These also co-circulated over
      long periods with intermittent changes of the predominant genotype. The prototype
      strain Ad3GB was isolated more frequently than five other Ad3 genotypes from 1981
      to 1988, after which a variant strain Ad3a was most common.

PMID- 8253225
TI  - Changing indications for penetrating keratoplasty, 1971-1990.
AB  - We report a retrospective analysis of the clinical indications for 3555
      penetrating keratoplasties performed at our department between 1971 and 1990. The
      cases were distributed among 12 diagnostic categories. Regrafting was the most
      common indication overall, accounting for 1452 cases (40.8%). Other major
      indications were, in order of decreasing frequency, keratoconus (17%), scarring
      secondary to herpes simplex keratitis (11.7%), aphakic bullous keratopathy (5.9%)
      and interstitial keratitis (5%). Further analysis of the relative percentages in
      each category within each 5-year interval of the study period was carried out to
      identify any changes in incidence. Viral disease as an indication for penetrating
      keratoplasty has shown a gradual decrease in frequency, accounting for only 6.4%
      of the cases during the last 5-year period (1986-90) compared with 19.6% during
      the first 5 years (1971-75). This finding is consistent with the marked
      improvement in the recognition and medical treatment of herpes simplex keratitis.
      The increase in incidence of grafting for pseudophakic bullous keratopathy in
      1986-90 (6.7%) compared with 1981-85 (1.1%) correlates well with the dramatic
      increase in the number of cataract extractions with intraocular lens
      implantations performed during that period.

PMID- 8253226
TI  - The National Cataract Surgery Survey: II. Clinical outcomes.
AB  - The short-term clinical outcomes of cataract extraction (within the context of
      established microsurgical practice) for a sample of all patients undergoing
      cataract surgery in the United Kingdom in 1990 are presented. Change in best
      corrected Snellen visual acuity 3 months after surgery and the occurrence of
      surgically related complications were taken as clinical indicators of outcome.
      Overall 80% (n = 764) of patients achieved a best corrected postoperative visual
      acuity of 6/12 or better at 3 months. Surgically related complications occurred
      in 7% (n = 71) of all patients in the intra-operative period, in 22% (n = 224) in
      the immediate post-operative period, in 18% (n = 176) at the first post-operative
      out-patient assessment and in 20% (n = 200) of patients at 3 months after
      surgery. Co-existing ocular pathology was identified as a risk factor for both
      poor visual outcome and the occurrence of complications. Increasing severity of
      ocular pathology was associated with increased risk of poor outcome. These
      results represent the first national figures for the short-term clinical outcomes
      of cataract surgery with respect to the current surgical practice in the United
      Kingdom.

PMID- 8253227
TI  - Trabeculectomy in diabetic patients with glaucoma.
AB  - Forty-one eyes of 41 patients with diabetes mellitus who underwent trabeculectomy
      over a 4-year period were compared with 41 age- and sex-matched controls, who
      were also matched for date of operation and surgical technique. The two groups
      were comparable for glaucoma diagnoses, duration of glaucoma before admission and
      number of ocular hypotensive medications. The intraocular pressures at diagnosis
      and on admission were similar. Post-operative complications were equally
      frequent. The mean intraocular pressure at 6 months was significantly lower in
      the control group, and fewer diabetic patients achieved either an intraocular
      pressure < 21 mmHg or successful drainage (defined as an intraocular pressure <
      21 mmHg on no treatment) at 6 months and at the final visit, after similar
      periods of follow-up. Trabeculectomy in diabetic patients with pre-existing
      retinopathy resulted in a significantly higher intraocular pressure at 6 months
      than when no retinopathy was present.

PMID- 8253228
TI  - The effect of topical pilocarpine on pulsatile ocular blood flow.
AB  - Ocular blood flow is considered an important factor in determining the extent of
      visual damage occurring in primary open angle glaucoma (POAG). The effect of
      topical pilocarpine, a parasympathomimetic vasodilator, on the pulsatile ocular
      blood flow (POBF) in POAG subjects was studied. A pneumotonometer linked to the
      Langham Ocular Blood Flow System recorded the intraocular pressure (IOP) pulse
      from which POBF was calculated. Measurements were taken from 18 POAG subjects
      treated with both G pilocarpine and G timolol, 2 weeks after withdrawing G
      pilocarpine and again 1 week after reinstituting full treatment. Recordings from
      20 POAG patients treated with only G timolol were taken as control values. There
      was no significant difference in the IOP or POBF between the controls and POAG
      patients on dual therapy. Furthermore when G pilocarpine was temporarily
      withdrawn there was no significant change in POBF despite a significant rise in
      IOP. The results imply that aqueous pilocarpine has no direct effect on the
      pulsatile component of ocular blood.

PMID- 8253229
TI  - Pilocarpine drops do not reduce intraocular pressure sufficiently in
      pseudoexfoliation glaucoma.
AB  - The reason for the poorer prognosis of pseudoexfoliation syndrome glaucomas
      (PXSG) compared with primary open angle glaucomas (POAG) is not fully understood.
      An open, comparative, cross-over study was performed in 15 patients (= eyes) with
      POAG and 15 patients (= eyes) with PXSG. Two different pharmacokinetic principles
      of drug administration were applied to uncover possible differences in short-term
      (hours) response to topical antiglaucomatous treatment. Intermittent pilocarpine
      drop medication (2%) and continuous low-dose pilocarpine delivery by a membrane
      controlled Ocusert unit (P40) were used. The 'carry-over' pressure reduction of
      an ordinary four times a day drop medication was significantly less effective in
      controlling the morning intraocular pressure (9 a.m.) in PXSG than in POAG. The
      duration of action of pilocarpine drops was reduced in PXSG. Defining
      'normotensive' pressure as < or = 20 mmHg, only 1 of the 15 PXSG eyes (6.7%)
      reached a normotensive level in the morning, compared with 8 of the 15 POAG eyes
      (53.3%). Using a continuous supply of pilocarpine (Ocusert), no differences
      between POAG and PXSG eyes were found. The study demonstrates the insufficient
      control of intraocular pressure in PXSG, compared with POAG, by identical
      antiglaucomatous drop medications. This may suggest an insufficient depot
      function of topical drugs in PXSG. In consequence, pseudoexfoliation material
      (PXM) must be sought in eyes with glaucoma, as PXM eyes will probably benefit
      from a more intense medical treatment compared with eyes without PXM.

PMID- 8253230
TI  - Laser surgery for glaucoma: minimally invasive therapy.

PMID- 8253231
TI  - Fungal corneoscleritis complicating beta-irradiation-induced scleral necrosis
      following pterygium excision.
AB  - Four cases of fungal corneoscleritis complicating beta-irradiation-induced
      scleral necrosis after pterygium excision have presented to our institution in
      recent years. Two cases were due to Petriellidium boydii and one each to Fusarium
      and Scedosporium inflatum. The condition may remain undiagnosed for weeks to
      months and becomes chronic with perforation or incipient perforation. The
      infections may masquerade as a chronic red eye, posterior scleritis or serous
      retinal detachment. Penetrating or lamellar keratoplasty is required following
      debridement of necrotic tissue. Prolonged systemic antifungal therapy may still
      fail to eradicate infection. Visual outcome is usually poor, and one of our
      patients required enucleation. Removal of calcific plaques from ulcer beds should
      be accompanied by disinfection, debridement and culture, since these beds and
      plaques are frequently a nidus of infection. Subsequently these ulcers may be
      covered with lamellar grafts or conjunctiva. We would caution against the use of
      radiotherapy to prevent recurrence of pterygia.

PMID- 8253232
TI  - Infective endophthalmitis following vitreoretinal surgery.
AB  - Eleven cases of endophthalmitis occurring after vitreoretinal surgery are
      described. At Moorfields Hospital, London, from 1986 to 1990 the incidence of
      endophthalmitis after explant surgery with or without drain was 0.19% and after
      vitrectomy was 0.15%. We conclude that the parity may be due to the intraocular
      instrumentation of most conventional retinal detachment repair procedures. The
      best indicator of poor prognosis was speed of onset of symptoms, those with rapid
      evolution having the worst outcome; 2 of these cases were enucleated. Those
      presenting at 2-3 days had the best outcome, consistent with infection due to a
      less virulent organism. Delays in diagnosis were in part due to the posterior
      location of signs of infection. Potential risk factors amenable to prophylactic
      strategy were identified in 10 of the 11 patients. Supplementary prophylaxis
      using ciprofloxacin or imipenem is proposed for cases with an identifiable risk
      factor. After systemic administration these antibiotics achieve vitreous levels
      that exceed the MIC90 of the commonest causative pathogens.

PMID- 8253233
TI  - Acanthamoeba trophozoite and cyst adherence to four types of soft contact lens
      and removal by cleaning agents.
AB  - Trophozoite and cyst adherence of two Acanthamoeba keratitis strains (PHL/530 and
      PHL/978) to four types of unworn soft contact lens and their removal by cleaning
      agents were studied. Greater adherence of the trophozoites compared with the
      cysts was recorded for both strains. Trophozoites of PHL/530 adhered in greater
      numbers to type I lenses (61.4% poly[2-hydroxyethyl methacrylate-38.6% water),
      with no differences between type II (30% lidofilcon A-70% water), III (55%
      bufilcon A-45% water) and IV lenses (42% etafilcon A-58% water). Adherence of
      PHL/978 trophozoites to type II lenses was decreased compared with their
      adherence to the other lenses. Cysts of both strains showed greater adherence to
      type I and III lenses. Interstrain differences in trophozoite adherence occurred,
      with PHL/530 showing greater adherence to type I and II lenses. Recommended
      cleaning procedures using three commercial solutions were effective in removing
      Acanthamoeba from the lenses. This study indicates the possible role of adherence
      to contact lenses in the acquisition of Acanthamoeba keratitis, but shows that
      correct use of commercial cleaning agents may be important in the prevention of
      infection.

PMID- 8253234
TI  - Intraocular malignant melanomas presenting with orbital inflammation.
AB  - Symptoms and signs of orbital inflammation may be prominent features in the
      presentation of choroidal malignant melanoma, even when the tumour is solely
      intraocular. Three cases with this clinical presentation are described.

PMID- 8253235
TI  - Canalicular infection caused by Actinomyces.
AB  - We present 7 cases of canalicular involvement with Actinomyces collected over a 5
      year period. All patients had involvement of one canaliculus, upper or lower,
      with lacrimal drainage patent to syringing. Curettings obtained by incising the
      involved canaliculi yielded Actinomyces species (5 cases) and Arachnia propionica
      (2 cases), typically in association with a mixed bacterial growth. Our results
      show that these patients often remain undiagnosed for months or even years, and
      are treated inappropriately for their recurrent symptoms. Despite sensitivity of
      Actinomyces to a broad spectrum of antibiotics, medical therapy alone does not
      eradicate the disease, and surgical evacuation of all concretions is essential to
      achieve a cure.

PMID- 8253236
TI  - Functional endoscopic transnasal dacryocystorhinostomy.
AB  - Endoscopic nasal surgical techniques are revolutionising the management of nasal
      and sinus disorders. Historically the surgical approach to the nasolacrimal sac
      and duct has been indirect by an external approach because of poor visualisation
      intranasally. The nasolacrimal apparatus is, however, intimately related to the
      lateral nasal wall and may readily be approached using an endoscopic technique
      which minimises functional interference with the physiological action of the
      lacrimal pump. This paper describes a technique of endoscopic intranasal
      dacryocystorhinostomy which has success rates comparable to those obtained by the
      more conventional external approach.

PMID- 8253237
TI  - Management of symptomatic latent nystagmus.
AB  - Most patients with latent nystagmus are asymptomatic and do not require
      treatment. We discuss the management by botulinum toxin injection and surgery of
      five cases of latent nystagmus in which the patients suffered loss of visual
      acuity on certain manoeuvres as a consequence of an exacerbation of the nystagmus
      amplitude. The importance of eye movement recordings for accurate diagnosis is
      stressed and the investigative role of botulinum toxin injection is discussed.
      Extraocular muscle surgery is helpful in some cases of symptomatic latent
      nystagmus.

PMID- 8253238
TI  - Computerised perimetry with moving and steady fixation in children.
AB  - The computer assisted moving eye campimeter (CAMEC) maintains the patient's
      interest and fixation by using a moving fixation target which must be tracked by
      the patient using a joystick for the test to proceed. In this study, 32 children
      were examined with the blind spot test programs of both CAMEC and the Dicon Auto
      Perimeter. Among those who completed both tests the blind spot was detected in 18
      eyes (75%) by the Dicon Auto-Perimeter and in 24 eyes (100%) by CAMEC. The mean
      CAMEC score (61.0%) was significantly higher than the mean Dicon Auto-Perimeter
      score (26.6%). CAMEC allowed better detection and quantification of scotomas in
      patients more than 4 years of age.

PMID- 8253239
TI  - Assessment of the value of congenital hypertrophy of the retinal pigment
      epithelium as an ocular marker for familial adenomatous polyposis coli.
AB  - The presence of bilateral, multiple patches of congenital hypertrophy of the
      retinal pigment epithelium (CHRPE) is cited as an early phenotypic marker of the
      familial adenomatous polyposis coli (FAPC) gene. However, the degree of
      concordance between CHRPE and the presence of familial adenomatous polyposis
      (FAP) has not been adequately assessed in individual families. We studied the
      eyes of 28 members of a single kindred spanning three generations with FAPC; 14
      were affected and 14 unaffected but 'at risk'. Six affected and 8 unaffected at
      risk individuals possessed a total of 34 retinal lesions, 17 in each group. Two
      affected individuals and 1 at risk individual had the classical pattern of CHRPE
      associated with FAPC. The sensitivity of CHRPE as an ocular marker for FAPC in
      this kindred was 14.2%. Our findings have implications for the use of CHRPE for
      the presymptomatic screening of family members at risk of FAPC. Therefore, ocular
      examination should not replace colonoscopic screening in an individual at risk of
      FAPC.

PMID- 8253240
TI  - Diagrammatic representation of strabismus.

PMID- 8253241
TI  - Analysis of retro-illumination photographs for use in longitudinal studies of
      cataract.
AB  - Retro-illumination photography has potential for the monitoring of cortical and
      posterior subcapsular cataract formation. Variations in the individual
      illumination results have limited accurate quantification of opacities within
      such images. We present a new image analysis technique which minimises the effect
      of uneven and varying retro-illumination. The new technique has been tested for
      variation between photographers and over a short time period. We believe it is of
      value in lens assessment in combination with a semi-quantitative grading system.

PMID- 8253242
TI  - Is post-cataract mydriasis necessary?
AB  - We report the results of a randomised prospective trial of post-operative
      cyclopentolate in patients who had uncomplicated endocapsular cataract
      extraction. We found no significant difference in visual acuity, intraocular lens
      centration or pupil area achieved after dilatation with tropicamide. There was a
      marked increase in the incidence of posterior synechiae in the group receiving
      cyclopentolate (33% vs. 13%).

PMID- 8253243
TI  - Childhood blindness in the West Bank and Gaza Strip: prevalence, aetiology and
      hereditary factors.
AB  - A study of all the schools for the blind in the West Bank and Gaza Strip was
      undertaken during 1991-2. Two hundred and five children had a complete ophthalmic
      examination. This represented 94% of all children aged 5-15 years attending
      schools for the blind. According to WHO categories of visual loss, 63% were blind
      and 21% had severe visual impairment. The main causes of blindness and severe
      visual loss were retinal (52%), optic atrophy (12%), glaucoma (9%) and cataract
      (7%). Common retinal diseases included degenerative myopia, Leber's congenital
      amaurosis, cone dystrophy and retinitis pigmentosa. Depending on the locality, 44
      85% of these children were the product of a consanguineous marriage and a
      positive family history was present in 57%. The minimum prevalence of childhood
      blindness was estimated to be 0.32/1000 children. A reduction in the prevalence
      of blindness requires a reduction in consanguineous marriages, genetic
      counselling for affected families and public health measures to ensure early
      referral for management of cataract and glaucoma.

PMID- 8253244
TI  - The effect of topical corticosteroids on refraction and corneal haze following
      excimer laser treatment of myopia: an update. A prospective, randomised, double
      masked study.
AB  - Several thousands of myopic patients have undergone photorefractive keratectomy
      (PRK) worldwide (prior to the publication of long-term, carefully controlled
      studies). The evidence in support of the currently widespread use of topical
      corticosteroids after PRK, however, is limited. We report the results of a
      prospective, double-masked trial to determine the effect of dexamethasone 0.1% on
      refraction and anterior stromal haze following -3.00 and -6.00 dioptre PRK
      procedures (n = 113; minimum follow-up 1 year). Initially the reduction in myopia
      was significantly greater in the steroid group compared with the placebo group (p
      < 0.002). However, on discontinuing the corticosteroids at 3 months this
      difference became statistically insignificant (p > 0.2). There was no
      statistically significant effect on anterior stromal haze at any stage. We
      conclude that, in view of their side effects, it would be unacceptable to use
      topical corticosteroids in the long term to maintain the initial beneficial
      effect on refraction. We therefore consider that topical corticosteroids should
      not be used following PRK.

PMID- 8253245
TI  - Chloroquine retinopathy in Nigerian patients with heart block.
AB  - Twenty-six patients with heart block were examined for evidence of chloroquine
      retinopathy. Detailed histories of chloroquine intake showed that 50% (13 of 26)
      of these patients were chloroquine abusers. Retinal changes typical of
      chloroquine retinopathy were seen in 53.8% (7 of 13) of the chronic chloroquine
      abusers. Patients with heart block of unknown cause should have their fundi
      examined so that signs of chloroquine retinopathy may be sought.

PMID- 8253246
TI  - Development of atypical amiodarone keratopathy in a corneal graft.
AB  - The presence of fine epithelial deposits in a whorled pattern (cornea
      verticillata) as a consequence of treatment with amiodarone is well documented.
      We present a case of amiodarone keratopathy in a grafted cornea which is atypical
      in that the orientation of the pattern is rotated through nearly 90 degrees to
      that normally observed. This observation runs counter to the hypothesis that
      cornea verticillata is a manifestation of the line of lid closure. We speculate
      on the mechanism directing the migrational pathways of epithelial cells.

PMID- 8253248
TI  - Use of a glass rod in argon laser suture cutting after trabeculectomy.

PMID- 8253247
TI  - Cavernous haemangioma of the orbit: treatment by transconjunctival
      cryoextraction.

PMID- 8253249
TI  - A model eye to practice indentation during indirect ophthalmoscopy.

PMID- 8253250
TI  - OKP Glaucoma Visual Field Test.

PMID- 8253251
TI  - Cellular automata.

PMID- 8253252
TI  - Peribulbar anaesthesia.

PMID- 8253253
TI  - Familial adenomatous polyposis in Delaware.

PMID- 8253254
TI  - Radiograph of the month. Appendiceal perforation with appendicolith.

PMID- 8253255
TI  - Proposed health care reform plan for Delaware.

PMID- 8253256
TI  - Initial affects of the expanded AIDS case definition.

PMID- 8253257
TI  - New choice in form of organizing a group medical practice.

PMID- 8253258
TI  - Consumer Health Library one year old.

PMID- 8253259
TI  - Two ideas for new physicians.

PMID- 8253260
TI  - Update on lung cancer.

PMID- 8253261
TI  - Summary of health-related legislation 137th General Assembly.

PMID- 8253262
TI  - Testimony on health care reform to the Delaware Health Care Commission.

PMID- 8253263
TI  - The lament of our times: health care crisis.

PMID- 8253264
TI  - Registered Limited Liability Partnership Act.

PMID- 8253265
TI  - HGF-induced tubulogenesis and branching of epithelial cells is modulated by
      extracellular matrix and TGF-beta.
AB  - Beginning with the observation that hepatocyte growth factor (HGF) induces the
      formation of branching tubular structures in Madin-Darby canine kidney (MDCK)
      cells cultured in Type I collagen gels but not in basement membrane Matrigel, we
      examined the individual components within this complex basement membrane extract
      to determine the effect of these proteins on the morphogenetic changes mediated
      by HGF. After extraction of several growth factors from Matrigel, HGF was still
      unable to induce process formation, an early event in tubulogenesis, indicating
      that one or more of the remaining extracellular matrix (ECM) proteins or growth
      factors were exerting the inhibitory effect. By individually adding back these
      components to MDCK cells grown in Type I collagen gels in the presence of HGF, we
      were able to establish that: (1) certain ECM proteins, such as laminin, entactin,
      and fibronectin, actually facilitated the formation of branching tubular
      structures and increased their complexity; (2) other ECM proteins, such as Type
      IV collagen, heparan sulfate proteoglycan, and vitronectin, caused marked
      inhibition of HGF-induced morphogenesis; and (3) not only did transforming growth
      factor-beta (TGF-beta) inhibit the formation of tubular structures, but those
      which did form exhibited little branching, thereby suggesting that TGF-beta
      modulates tubulogenesis as well as branching. These results suggest that a
      tubulogenic morphogen such as HGF and a tubulogenesis-inhibitory morphogen such
      as TGF-beta can, in the context of the dynamic matrix known to exist during
      epithelial tissue development, modulate the degree of tubule (or ductal)
      formation, the length of these tubules, and the extent of their arborization. The
      relevance of these findings to tubulogenesis and branching during kidney
      development is discussed.

PMID- 8253266
TI  - Cell wall and rhizoid polarity in Pelvetia embryos.
AB  - The developmental potentials of the rhizoid and thallus cells of two-celled
      Pelvetia embryos were investigated. Ablation of either the thallus or the rhizoid
      cell was accomplished by puncture with a micropipette. Thallus cells continued to
      divide repeatedly after rhizoid ablation, and in no case did the thallus initiate
      new rhizoid growth. In the reciprocal experiment, rhizoid cells elongated and
      divided in the normal transverse orientation after ablation of the thallus cell.
      The rhizoid did not appear to initiate a new thallus. Similar results were
      obtained when laser irradiation was applied to arrest division in one of the two
      cells. Thus, neither thallus nor rhizoid cell compensated for ablation or arrest
      of its sibling cell. The role of the cell wall-plasma membrane connections in
      organizing polar growth in the rhizoid cell was investigated by separating the
      wall from the protoplast. This was accomplished in two ways, by plasmolysis and
      by enzymatic wall digestion. Wall digestion yielded rhizoid cell protoplasts
      capable of wall regeneration and division, but the polar growth habit was
      irreversibly lost. Loss of polar growth correlated with loss of polarity in the
      microtubule cytoskeleton as visualized by indirect immunofluorescence using
      confocal microscopy. Transient plasmolysis of rhizoid cells resulted in
      abandonment of the preexisting apex and the initiation of a new rhizoid tip after
      rehydration. We suggest that interaction between the cell wall and the plasma
      membrane is involved in organizing polar growth.

PMID- 8253267
TI  - Molecular and genetic characterization of the Drosophila tartan gene.
AB  - Here we report the discovery and characterization of the Drosophila tartan gene.
      tartan is transcribed in an unusual embryonic pattern of intersecting stripes
      which are generated in response to the anterior-posterior and dorsal-ventral
      regulatory systems. tartan encodes a putative transmembrane protein containing
      extracellular leucine-rich repeats characteristic of numerous cell surface
      receptors and adhesion proteins. Its expression is correlated with aspects of
      segmentation and neurogenesis, including the formation of neuroblasts, sensory
      mother cells, and peripheral nerves. Mutants homozygous for a recessive lethal
      tartan loss-function allele exhibit defects in the position and number of cells
      within peripheral sense organs, the routing of peripheral nerves, and the
      organization of commissures within the central nervous system. Mutants are also
      defective in muscle organization. These results suggest that tartan is required
      for cell surface interactions important for normal organization of epidermal and
      subepidermal structures.

PMID- 8253268
TI  - Hypoangular: a gene potentially involved in specifying positional information in
      a ciliate, Tetrahymena thermophila.
AB  - In Tetrahymena, two unique cell-surface structures, the oral apparatus and the
      cytoproct, are formed at opposite ends of one ciliary row, the reference
      meridian, which is propagated longitudinally during clonal growth. A third set of
      unique structures, the contractile vacuole pore(s) (CVP), is located at a nearly
      constant proportion of the cell circumference to the cell's right of the
      reference meridian. Three allelic recessive temperature-sensitive mutations,
      collectively named hypoangular (hpo), alter both the geometry of propagation of
      the reference meridian and the location of the CVPs. In mutant cells, the
      reference meridian typically undergoes a steady rightward shift in successive
      cell generations ("cortical slippage"); concomitantly, CVP sets come to lie
      closer to the reference meridian. Although CVP location is still proportional to
      the cell circumference, the constant of proportionality (the "CVP angle") is
      reduced. Another effect is an alteration in the widths of morphogenetic domains
      within the cortex. As the temperature is raised (made more restrictive), these
      effects are accentuated and the CVP angle becomes reduced further. At the
      extreme, the CVP angle collapses to zero and less, i.e., there is a topological
      switch such that CVPs come to lie to the left of the reference meridian, and the
      direction of cortical slippage reverses from rightward to leftward. These
      observations are hard to reconcile with existing formal models of pattern
      specification in this system and suggest that the hpo locus might specify a key
      component of the intracellular positional system.

PMID- 8253269
TI  - Planar polarity in the ciliated epidermis of Xenopus embryos.
AB  - The coordinated orientation of ciliary beat in the larval epidermis of
      amphibians, evident in an organized streamline pattern, suggests a planar
      polarity of the epithelium, i.e., a polarity within the plane of the cell sheet.
      It has been proposed that the direction of ciliary beat is determined at mid
      gastrula by a gradient of a diffusible factor produced by the mesoderm. To
      analyze whether ectoderm in isolation can establish a uniform direction of
      ciliary beat, and at what stage its polarity is specified in the embryo, ectoderm
      of Xenopus laevis embryos of different stages was cultured in vitro on
      substrates. On concanavalin A, ectoderm isolated at early gastrula stages, i.e.,
      prior to any contact with mesoderm, can autonomously coordinate the direction of
      ciliary beat, at least in small regions. A uniform planar polarity is expressed
      by ectoderm explanted from the early mid gastrula onward. On fibronectin, which
      promotes migration, the direction of movement correlates well with the direction
      of ciliary beat, and directional migration can even override the inherent
      polarity specified prior to explantation. Embryos which lack dorsal mesoderm
      nevertheless develop a highly organized streamline pattern, excluding a strict
      requirement for dorsal mesoderm for the determination of planar polarity.
      However, in spite of the early specification of planar polarity found for
      isolated tissue, rotated ectodermal transplants in situ can readjust their
      polarity in accordance with that of the host.

PMID- 8253270
TI  - The embryonic ciliated band of the sea urchin, Strongylocentrotus purpuratus
      derives from both oral and aboral ectoderm.
AB  - The ciliated band of the Strongylocentrotus purpuratus embryo consists of a
      columnar epithelium, 3-5 cells wide, which gives rise to a small number of
      neuroblasts. It arises late in development, as a border separating the squamous
      epithelial cells of the oral and aboral ectoderm. To determine the lineage
      origins of this structure, we performed double labeling experiments at the 2-cell
      stage and the 16-cell stage, which were designed to reveal clonal boundaries in
      the ciliated band. The ciliated band forms in a region of the ectoderm derived
      from descendants of the following blastomeres: No, VO, Na1u, Na2u, right and left
      NL1u, and right and left NL2u. In contrast to the lineage contributions of the
      embryonic territories established early in development, lineage origins of the
      ciliated band are variable. Specification of the ciliated band thus depends on
      intercellular interaction rather than lineage.

PMID- 8253271
TI  - Cell adhesion molecules and the migration of LHRH neurons during development.
AB  - During embryogenesis, LHRH neurons arise in the olfactory epithelium, migrate
      along the olfactory nerve, and enter the forebrain. We have examined the
      distribution of several cell adhesion molecules (CAMs) in the developing chick
      olfactory system and brain to determine whether differential distributions of
      these adhesion molecules might be important in pathway choices made by migrating
      LHRH neurons. Single- and double-label immunocytochemical studies indicated that
      high levels of N-CAM and N-cadherin were expressed throughout the olfactory
      epithelium and not restricted to the medial half of the olfactory epithelium
      where most of the LHRH neurons originate. Further, high levels of N-CAM, Ng-CAM,
      and N-cadherin were uniformly expressed throughout the entire olfactory nerve
      while migrating LHRH neurons were confined to the medial half of the nerve.
      However, once LHRH neurons reach the brain, they migrate dorsally and caudally,
      tangential to the medial surface of the forebrain, along a region enriched in N
      CAM and Ng-CAM. After this first stage of migration within the brain, LHRH
      neurons migrate laterally. At this stage, there is no correlation between the
      intensity of N-CAM and Ng-CAM immunostaining and the location of LHRH neurons.
      These results suggest that N-CAM, Ng-CAM, and N-cadherin do not play a guiding
      role in LHRH neuronal migration through the olfactory epithelium and olfactory
      nerve but that migrating LHRH neurons may follow a "CAM-trail" of N-CAM and Ng
      CAM along the medial surface of the forebrain.

PMID- 8253272
TI  - Molecular analysis of the initiation of insect metamorphosis: a comparative study
      of Drosophila ecdysteroid-regulated transcription.
AB  - More than 50 ecdysteroid-regulated Drosophila genes have been described in the
      literature. These genes were identified using several different ecdysteroid
      responsive systems and characterized under a variety of experimental conditions.
      The diversity of these approaches has made it difficult to compare results and
      identify common responses to the hormone. As a first step toward characterizing
      the temporal regulation of these genes by ecdysteroids, we have examined their
      transcriptional activity throughout third instar larval and prepupal development
      using a single collection of staged animals. We see four coordinate changes in
      ecdysteroid-regulated gene activity during third instar larval development, at 78
      88 hr, approximately 100 hr, 106-108 hr, and approximately 114 hr after egg
      laying. A dramatic transition in gene expression occurs at puparium formation,
      after which the prepupal ecdysteroid pulse induces successive waves of
      transcription. Our results suggest that several increases in the ecdysteroid
      titer during third instar larval and prepupal development program a precise
      temporal progression of gene activity that could direct the appropriate
      behavioral and developmental changes at the onset of metamorphosis.

PMID- 8253273
TI  - Oocytes preserve the ability of mouse cumulus cells in culture to synthesize
      hyaluronic acid and dermatan sulfate.
AB  - A soluble factor(s) produced by fully grown oocytes is essential, together with
      follicle stimulating hormone (FSH), to stimulate in vitro hyaluronic acid (HA)
      synthesis by mouse cumulus cells (CCs). The stability of the response to this
      stimulus by CCs in culture was investigated. The data showed that preculture for
      8 hr in basal medium reduced to approximately 30% the ability of CCs to
      synthesize HA in response to FSH or dibutyryl cyclic AMP (Bt2cAMP) and soluble
      oocyte factor(s). However, if CCs were precultured for the same period of time as
      intact cumulus cell-oocyte complexes, or in the presence of fully grown oocytes,
      or in medium conditioned by fully grown oocytes, their ability to synthesize HA
      was 75-95% preserved. In vitro stimulation of dermatan sulfate (DS) synthesis by
      CCs does not require oocyte factors and is induced by FSH or Bt2cAMP treatment
      alone. However, the preservation of such activity, like that of HA synthesis,
      depended on the presence of a soluble oocyte factor(s) during preculture. The
      presence of isolated oocytes or of oocyte-conditioned medium also prevented the
      spreading of CCs in culture. However, inhibiting CC spreading by culture on agar
      coated plates or in serum-free medium did not preserve their HA or DS synthetic
      activity, thus suggesting that the two oocyte actions on CCs are independent.
      Growing oocytes were unable both to induce HA synthesis in freshly isolated CCs
      stimulated with FSH and to preserve the ability to synthesize HA and DS in 8-hr
      precultured CCs. The results suggest that the stability of the differentiated
      state of mouse CCs in vitro depends upon continued exposure to a soluble
      factor(s) produced by fully grown oocytes.

PMID- 8253275
TI  - Induction of normal cardiovascular development in the vitamin A-deprived quail
      embryo by natural retinoids.
AB  - The biological activity of various natural retinoids and the time "window" when
      vitamin A activity is required for normal cardiovascular development were
      examined in vitamin A-deprived Japanese quail embryos. The administration of 1
      microgram of retinol at the beginning of incubation resulted in normal
      cardiovascular development in 97% of embryos; retinoic acid was toxic at this
      dose level. Treatment of embryos with 0.1 microgram of all-trans-retinol or 13
      cis-retinoic acid at the beginning of incubation resulted in normal
      cardiovascular development in 47 and 12% of embryos, respectively; administration
      of these retinoids at other time points attenuated the percentage of embryos with
      normal cardiovascular development. Didehydroretinol, 0.1 microgram, and 9-cis
      retinoic acid, 0.1 microgram, were inactive at all time points examined; 9-cis
      retinoic acid did not enhance the biological activity of all-trans-retinoic acid.
      All-trans-retinoic acid, 0.1 microgram, administered during 22-28 hr of
      incubation induced normal cardiovascular development in 20-34% of embryos;
      biological activity was optimal when it was administered at 24 hr. All retinoids
      tested were inactive in establishing normal cardiovascular development when
      administered at 36 hr of incubation or later. The studies suggest that all-trans
      retinoic acid is the biologically active form of vitamin A required for normal
      cardiovascular development in the avian embryo. There is a critical time point
      within the first 22-28 hr of quail embryogenesis when all-trans-retinoic acid
      initiates events that lead to normal cardiovascular development.

PMID- 8253274
TI  - XFKH2, a Xenopus HNF-3 alpha homologue, exhibits both activin-inducible and
      autonomous phases of expression in early embryos.
AB  - We have isolated the Xenopus fork head (fkh) box-containing gene XFKH2. XFKH2
      appears to be most similar to the rat liver transcription factor HNF-3 alpha,
      with 64% amino acid identity throughout the protein and 96% amino acid identity
      within the fkh box. Dissection experiments demonstrate that XFKH2 is present in
      the vegetal pole and marginal zone but not the animal pole of gastrulae and in
      equal levels in the dorsal and ventral halves of both gastrulae and neurulae. By
      in situ hybridization, we know that the dorsal component of expression is
      concentrated in the notochord in neurulae. In tailbud embryos, XFKH2 is detected
      in the foregut, the brain, and in two lines of cells just dorsal and ventral to
      the notochord, the hypochord and the floor plate of the spinal cord. Finally,
      although explanted animal caps will turn on XFKH2 autonomously at midneurula
      stage, activin induces early expression at gastrula stage. The early, growth
      factor-dependent expression does occur in the presence of the protein synthesis
      inhibitor cycloheximide, suggesting that XFKH2 expression during gastrula stage
      may be an immediate early response to mesoderm induction.

PMID- 8253276
TI  - NMDA receptor blockade alters the topography of naturally occurring ganglion cell
      death in the rat retina.
AB  - During the first 10 days after birth around half the rat's retinal ganglion cells
      die. Previous work has shown that ganglion cells whose axons have made large
      topographic targeting errors are preferentially eliminated during this period and
      that the selection of such cells for preferential elimination is dependent on an
      activity-driven mechanism: this process is one way in which the postnatal
      refinement of the topography of the retinocollicular projection is achieved. We
      have given systemic injections of the NMDA channel blocker MK801 during the first
      14 days of life to see whether this activity-dependent process works via the NMDA
      channel. We assessed the topographic pattern of retinal ganglion cell death by
      making localized injections of fast blue into the superior colliculus at birth
      and measuring the distribution of labeled ganglion cells either at Postnatal Day
      2 or at Day 14. We find that overall retinal ganglion cell death, measured by
      optic nerve axon counts, is not prevented by MK801 treatment. However, whereas in
      untreated animals ganglion cells whose axons have reached the most
      topographically inappropriate target area are preferentially eliminated, in MK801
      treated animals ganglion cell death appears to be random, in that we see no
      evidence of the preferential elimination of retinal ganglion cells whose axons
      have made large topographic targeting errors in MK801-treated animals. NMDA
      receptor blockade therefore has the same effect on the pattern of retinal
      ganglion cell death as tetrodotoxin blockade of the retina.

PMID- 8253277
TI  - Ultrastructure of developing flight muscle in Drosophila. I. Assembly of
      myofibrils.
AB  - In order to evaluate the effects of specific mutations on sarcomere assembly and
      function in vivo, we describe the course of normal development of Drosophila
      indirect flight muscle (IFM) in staged pupae using electron microscopy. We find
      that no contractile assemblies remain in larval muscle remnants invaded by
      imaginal myoblasts, establishing that myofibrils in IFM assemble de novo. Stress
      fiber-like structures or other template structures are not prominent before or
      during sarcomere assembly. By 42 hr pupation (eclosion approximately 112 hr),
      thick and thin filaments have appeared simultaneously in slender, interdigitated
      arrays between regularly spaced Z-bodies. Each tiny, uniformly striated myofibril
      forms within a "sleeve" of microtubules, and both microtubules and myofibrils are
      attached to the cell membrane at each end of the fiber from the initial stages of
      assembly. Later in pupation, the microtubule "sleeves" disassemble. Sarcomere
      number appears to remain constant. We saw no evidence that terminal sarcomeres
      are sites for addition of new sarcomeres or that Z-lines split transversely,
      producing new, very short sarcomeres. Rather, initial thick and thin filaments
      and sarcomeres are much shorter than adult length. Sarcomere length increases
      smoothly and coordinately from approximately 1.7 to approximately 3.2 microns,
      reflecting increase in filament lengths and indicating that myosin and actin
      molecules must be incorporated into filaments after sarcomere formation.
      Myofilaments are not seen scattered in the cytoplasm at any time, nor do we
      detect filaments that could be in the process of being "trolleyed" along
      myofibrils into positions of lateral register. Myofibril diameter increases
      uniformly from approximately 4-thick filaments to approximately 36-thick
      filaments across, by peripheral addition of myofilaments. At each successive
      stage, all sarcomeres in a fiber attained similar length and diameter. Initial
      thick filaments are solid but within several hours these and all subsequently
      assembled thick filaments appear hollow. Initial Z-bodies do not show any
      internal lattice and are more irregularly shaped than adult Z-discs.

PMID- 8253278
TI  - Ultrastructure of developing flight muscle in Drosophila. II. Formation of the
      myotendon junction.
AB  - Using ultra-thin section electron microscopy, the development of the myotendon
      junction (MTJ) of Drosophila indirect flight muscle (IFM) is described for the
      first time. The MTJ is a cell-cell junction between the IFM and epithelial tendon
      cells. The terminal Z-band of each myofibril forms a uniform junction with a
      tendon cell; each junction shows a precise sequence of folding and elaboration in
      which microtubule arrays in both cell types play a prominent role. Upon
      IFM/tendon cell contact (by approximately 32 hr pupation), numerous flat, focal
      dense plaques form between muscle and tendon cell membranes. In the muscle,
      transient arrays of microtubules, which will form "sleeves" around the developing
      myofibrils, delineate the perimeter of these focal plaques. Each of the dense
      plaques enlarges and develops into the modified terminal Z-band (MT-Z) of a
      myofibril, linking the thick and thin filaments of the highly ordered terminal
      sarcomere to the membrane via a dense feltwork. As these plaques develop into the
      MT-Z, the perimeter of each plaque advances, leaving the central region deeply
      indented. Between 50-75 hr pupation, secondary folds appear in each MTJ, and
      tendon cell microtubules that will form the tendon elements attach to specific
      dense sites on the secondary folds of the junctional membrane opposite the MT-Z.
      By 100 hr pupation, each MTJ develops numerous sharp folds, thereby tightly
      interdigitating the muscle and tendon cell. Amorphous density associated with the
      junctional membranes assumes a crystalline array that includes the membrane
      cytoskeletons of both cells and the extracellular matrix. At the end of pupation
      (approximately 112 hr), the final link between tendon cell and cuticle is formed
      as the tiny, dense-tipped microvilli in contact with the cuticle are replaced by
      extracellular tonofibrils, dense shafts that fill deep pits in the tendon cell
      and extend deeply into the cuticle. The tendon cell microtubules become bundled
      and decorated by fine "feather" filaments and the free ends of these microtubule
      bundles become linked to the membrane surrounding the pits.

PMID- 8253279
TI  - Suppression of head regeneration by accelerated wound healing in hydra.
AB  - Published evidence suggests that tissue injury is important for head regeneration
      in hydra [MacWilliams, 1982, 1983a,b; Kobatake and Sugiyama, 1989]. To
      investigate this problem in more detail, two experimental manipulations,
      decapitation and mirror-image grafting, were carried out. In the latter, two
      decapitated polyps were axially grafted to each other to make the wound openings
      of the two polyps juxtaposed on each other. In normal regenerates, the wound
      opening closed and healed in 4 to 5 hr, while in mirror-image grafts it healed in
      about 1 hr. The percentage of head regeneration was lower in mirror-image grafts
      than that after decapitation. The effect of mirror-image grafting on
      morphogenetic potential levels was examined using a lateral transplantation
      technique. Head inhibition levels dropped in both types of regenerates to a
      similar extent. Head activation levels rose more in normal regenerates than in
      mirror-image grafts. These results show clearly that the drop in head inhibition
      level is due to removal of the head and is not affected by grafting. They also
      show that the increase in head activation levels and in the percentage of head
      regeneration is affected substantially by the grafting. These observations are
      consistent with the view that decapitation produced a greater injury effect than
      mirror-image grafting, and this injury effect raised the head activation level
      whereas it did not alter the head inhibition level. The fact that the wound
      remained open for a longer time in normal regenerates than in the grafts suggests
      that the injury effect depends not on tissue injury itself but on the length of
      time the wound is open.

PMID- 8253280
TI  - Oscillation of intracellular free calcium in cleaving and cleavage-arrested
      embryos of Xenopus laevis.
AB  - Changes in the intracellular free calcium levels in the cortical region of
      cleaving Xenopus eggs were examined using semi-synthetic aequorin. We detected
      periodic oscillations in the free calcium levels accompanying the cleavage cycle
      as early as the first cleavage onward. The calcium levels began to increase at
      early interphase and were maximal during metaphase of mitosis. Eggs injected with
      colchicine to inhibit cleavage showed periodic oscillations in the calcium levels
      similar to those of normal eggs. This fact indicates that the furrowing process
      is not necessary for the periodic changes in the intracellular free calcium
      levels, but the changes are associated with the autonomous periodic cytoplasmic
      activity which controls cell cycle events.

PMID- 8253281
TI  - Reaction-diffusion control of heart development: evidence for activation and
      inhibition in precardiac mesoderm.
AB  - In axolotl embryos homozygous for the cardiac-lethal (c) gene, the heart never
      begins to beat. Recently, we demonstrated that the c gene affects the heart
      mesoderm directly, making the latter incapable of responding to normal inductive
      stimuli. Based on these results, we proposed that a reaction-diffusion mechanism
      controls the later stages of vertebrate cardiogenesis. In the present study, we
      use a series of transplantations to examine the precardiac mesoderm of wild-type
      and cardiac-lethal mutant axolotl embryos for the activation and inhibition
      predicted by our model. When one or both heart primordia in c/c embryos were
      replaced with +/+ tissue at early stages, functional hearts developed, indicating
      that an activator-like activity is present in wild-type heart mesoderm. At later
      stages, replacement of the entire heart-field mesoderm also rescued mutant
      embryos, but replacement of only the heart-forming mesoderm did not, indicating
      that the mutant heart field has inhibitory properties. These results demonstrate
      that activator- and inhibitor-like factors are present in pre-cardiac mesoderm
      and thus provide evidence for reaction-diffusion control of postinductive heart
      development.

PMID- 8253282
TI  - Creating maternal effect mutations in transgenic mice: antisense inhibition of an
      oocyte gene product.
AB  - Gene products present in mouse oocytes direct development until the two-cell
      stage and may be important in later development. Here, we demonstrate that
      expression of a specific maternal protein can be disrupted in mouse oocytes using
      transgenic antisense RNA technology. An oocyte-specific promoter (mZP3) was
      utilized to express antisense RNA directed against maternal mRNA encoding tissue
      type plasminogen activator (tPA). Antisense expression results in reduced levels
      of tPA mRNA and enzyme activity in mouse oocytes. We also provide evidence for a
      novel mechanism of antisense-mediated translational inhibition, whereby the
      cytoplasmic polyadenylation of maternal tPA mRNA is altered. This strategy should
      prove applicable to functional studies of other murine maternal mRNAs in an in
      vivo environment.

PMID- 8253283
TI  - Isolated vegetal cortex from Xenopus oocytes selectively retains localized mRNAs.
AB  - The process of converting an egg to a multicellular organism often begins with a
      polarization of information within the oocyte. The cytoskeleton plays an
      important role in maintaining such asymmetries. Here we describe the isolation
      and characterization of cortices, rich in cytoskeletal elements, from the animal
      and vegetal poles of stage VI Xenopus oocytes. Ultrastructural and
      immunocytochemical analyses revealed that the 10-microns-thick isolates included
      a cytokeratin network, mitochondria, and other elements, found in the oocyte
      cortex. Furthermore, three vegetally localized mRNAs, Vg1, Xcat-2, and Xcat-3,
      were all found to be specifically retained within the isolated vegetal cortices,
      in sharp contrast to histone RNA. Our findings support the view that the vegetal
      cortex represents a unique cytoskeletal domain in which a rare class of maternal
      mRNAs becomes localized.

PMID- 8253284
TI  - Nutrition and disability.

PMID- 8253285
TI  - Bilateral spastic cerebral palsy--a comparative study between south-west Germany
      and western Sweden. I: Clinical patterns and disabilities.
AB  - The results of a collaborative study of bilateral spastic cerebral palsy (BSCP)
      between south-west Germany and western Sweden are reported, comprising 249
      children in south-west Germany and 264 children in western Sweden. A severe gross
      motor disability was present in 65 per cent of the German and 62 per cent of the
      Swedish children; learning difficulties or mental retardation in 73 and 76 per
      cent; active epilepsy in 28 and 26 per cent; and severe visual disability in 20
      and 19 per cent, respectively. Severe disabilities were especially pronounced in
      children with normal birthweights, in whom the most severe subtypes of BSCP were
      also found. Leg-dominated BSCP was the predominant subtype among low-birthweight
      children, but also occurred in more than half of the normal-birthweight children.
      The authors conclude that the two series were comparable, and that reliable
      results between countries can be obtained if clear-cut classifications and
      definitions are used.

PMID- 8253286
TI  - Evaluation of the hip-extensor tricycle in improving gait in children with
      cerebral palsy.
AB  - Weakness of the hip extensor muscles contributes to the walking impairment of
      children with cerebral palsy, but it is difficult to strengthen these muscles.
      This study demonstrates greater activation of the hip extensor muscles when using
      a tricycle developed for this purpose than when using a traditional tricycle. The
      hip-extensor tricycle was also found to be more stable than a traditional
      tricycle. A 10-week field trial of the hip-extensor tricycle showed that visually
      analysed gait improved, but hip extensor strength did not. However, children used
      and enjoyed the tricycle, and parental reports were positive. This tricycle could
      be used to supplement other means of improving gait in children with CP.

PMID- 8253287
TI  - The effect of non-depot ACTH(1-24) on infantile spasms.
AB  - However, side-effects such as severe infections, hypertension and electrolyte
      imbalance have been found, assumed to be related to hypercortisolism induced by
      chronic ACTH treatment. The authors treated 18 patients with infantile spasms
      with non-depot ACTH(1-24). The therapeutic effect of non-depot ACTH was
      comparable to that of depot ACTH, with no severe bacterial infection or sepsis.
      The incidence of hypertension was significantly lower in the non-depot ACTH
      group, and persistent hypercortisolaemia was not found. Non-depot ACTH(1-24)
      appears to be as effective as ACTH(1-24) depot therapy in the treatment of
      infantile spasms, and its side-effects are mild. It would appear that the effect
      of non-depot ACTH is not mediated by hypercortisolism, but by a direct
      neurotropic effect on the brain.

PMID- 8253288
TI  - Nutritional assessment in Duchenne muscular dystrophy.
AB  - A specific-weight chart and simple clinical tools are sufficient to obtain an
      accurate diagnosis of undernutrition or obesity among patients with Duchenne
      muscular dystrophy (DMD). The authors collected weight-for-age measures from a
      sample of 252 boys and anthropometric data from 109 of those boys with DMD. The
      data confirm the accuracy of the DMD ideal-weight chart previously proposed by
      Griffiths and Edwards (1988). Obesity may occur from the age of seven years; its
      prevalence seems to reach 54 per cent by the age of 13 years. Undernutrition
      occurs after the age of 14 years, involving 54 per cent of boys at about 18 years
      of age. Obese boys show a centralized body-fat distribution, in agreement with
      other obese populations.

PMID- 8253289
TI  - Some aspects of the reliability of Touwen's examination of the child with minor
      neurological dysfunction.
AB  - Three studies concerning the inter-rater and test-retest reliability of the
      Touwen examination are presented. The results of the first study showed that it
      was not possible to achieve acceptable levels of reliability using the manual as
      the only reference for instruction. Although the reliability estimates of the
      total scores were good, inter-rater reliability for the nine groups of items and
      the individual tasks within them was poor. When methodology and interpretation of
      performance was agreed between observers, a second study showed that these
      disagreements diminished. The third study demonstrated that the short-term
      stability of total scores is good, but reliability for group and individual item
      scores remained poor.

PMID- 8253290
TI  - Monocular nystagmus caused by unilateral anterior visual-pathway disease.
AB  - The authors examined five young children with monocular vision loss who developed
      monocular nystagmus. The nystagmus was of fast frequency and small amplitude in
      all fields of gaze. In four children, successful treatment of the cause of the
      vision loss resulted in cessation of the nystagmus. No child showed signs of
      spasmus nutans, or of optic nerve or chiasmal tumor. The evaluation of the young
      child with unilateral nystagmus should begin with a careful eye examination.

PMID- 8253291
TI  - Problems in relation to independent living: a retrospective study of physically
      disabled school-leavers.
AB  - Problems in relation to independent living were studied in a cohort of 80
      physically disabled young people on average five years after leaving school. 38
      per cent were living, or planned to live, independently. This group was more
      likely to be of average intellectual ability and to have a physical impairment
      other than cerebral palsy. Of the 35 per cent who felt that their physical
      disabilities were such that they would be unable to manage without care from
      parents in the family home, at least 80 per cent needed daily help with personal
      hygiene, dressing and travel. 90 per cent of the parents interviewed felt that
      their son or daughter should not live independently. Counselling of the young
      person and parent from an earlier stage to allow forward planning is recommended,
      and will be easier if there is a choice of accommodation and style of living
      available.

PMID- 8253292
TI  - Multivariate analysis: should the numbers speak for themselves?

PMID- 8253293
TI  - Effect of dose, time, and pretreatment on the biliary excretion and tissue
      distribution of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat.
AB  - Previous studies of the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)
      pretreatment on the biliary excretion and hepatic disposition indicated that TCDD
      did not induce its own metabolic elimination. Pretreatment with TCDD did enhance
      its hepatic uptake. The present work was designed to further examine the effects
      of dose, time, and pretreatment on the tissue distribution and biliary
      elimination of [3H]TCDD. Adult male F-344 rats were administered 0 or 100 nmol
      [14C]TCDD or [3H]-TCDD/kg body weight po 3 days prior to bile duct cannulation
      and iv injection of 0 or 1 nmol [3H]TCDD or 1, 10, or 100 nmol [14C]TCDD/kg. Bile
      was collected for up to 8 hr while rats were maintained under pentobarbital
      anesthesia. Biliary TCDD and TCDD metabolites were quantified by liquid
      scintillation spectrometry. In naive animals which received no pretreatment,
      similar rates of excretion (% dose) were observed following iv administration of
      1 nmol [3H]TCDD/kg or 10 or 100 nmol [14C]-TCDD/kg. Metabolic elimination of
      highly purified [3H]TCDD (> 99%) appeared to be linear with respect to time with
      approximately 0.8% of the dose being excreted in the bile over a 5- to 8-hr
      collection period 0 or 24 hr after iv dosing (1, 10, or 100 nmol/kg) and 72 hr
      after oral dosing (100 nmol/kg). In all groups, higher concentrations of TCDD
      were found in liver versus fat, and perirenal fat concentrations were elevated
      relative to epididymal fat concentrations, probably reflective of the enhanced
      blood perfusion of the former tissue. Pretreatment enhanced hepatic
      concentrations and decreased fat concentrations of the challenge dose.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8253294
TI  - Comparison of ELISA and plaque-forming cell assays for measuring the humoral
      immune response to SRBC in rats and mice treated with benzo[a]pyrene or
      cyclophosphamide.
AB  - The humoral immune response against sheep red blood cells (SRBC) is one of the
      most sensitive and frequently used end-points in evaluating the immunotoxicity of
      drugs and chemicals in experimental animals. Currently, most immunotoxicology
      studies measure the SRBC IgM antibody response by quantitating the number of SRBC
      specific IgM antibody-forming cells using the hemolytic plaque assay. On the
      other hand, measurement of serum SRBC-specific IgM could be an easier, more cost
      effective endpoint in evaluating the SRBC antibody response in rodents. A
      validated method to measure SRBC-specific IgM, however, has not been developed.
      Thus, the objectives of the studies presented were to develop and validate an
      enzyme-linked immunosorbent assay (ELISA) for SRBC-specific IgM. Hemoglobin-free,
      detergent-solubilized membrane preparations were chosen as antigen for the ELISA.
      Various sources of SRBC were found to be equally useful, and as little as 0.1
      micrograms of protein per well was optimal. Kinetic studies of the IgM response
      showed the peak day to be on Day 5 (mice) and Day 6 (rats). To validate the
      usefulness of the method for immunotoxicologic studies, serum SRBC-specific IgM
      levels and number of SRBC-specific plaque-forming cells were compared in rats and
      mice treated with two well-characterized immunosuppressive agents: benzo[a]pyrene
      and cyclophosphamide. Administration of these chemicals was found to produce very
      similar dose-dependent decreases in serum SRBC IgM and IgM-specific plaque
      forming cells. These two endpoints were equally sensitive to the effects of the
      immunosuppressive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253295
TI  - A two-generation reproduction study with hydroquinone in rats.
AB  - The effects of hydroquinone (HQ) on reproductive performance and fertility were
      assessed in a two-generation study with CD Sprague-Dawley rats (one litter per
      generation). HQ was administered in an aqueous solution by gavage at doses of 0,
      15, 50, and 150 mg/kg/day. F0 and F1 parental animals were dosed daily for at
      least 10 weeks prior to cohabitation, during cohabitation, and until scheduled
      termination. At all dose levels tested, no adverse effects were observed on feed
      consumption, survival, or reproductive parameters for the F0 or F1 parental
      animals. Mild, transient tremors were observed shortly after dosing at 150
      mg/kg/day in several F0 and F1 parental animals and in a single F0 male at 50
      mg/kg/day. These tremors occurred infrequently and were considered to be due to
      an acute stimulatory effect of HQ on the nervous system. Body weights for F0 and
      F1 parental females were similar between all dose groups throughout the study.
      Body weights for F0 parental males were also comparable to those of control
      throughout the study. Statistically significant differences in body weights were
      noted for the F1 parental males in the 50 and 150 mg/kg/day dose groups at
      several intervals during the premating, mating, and postmating periods. No
      treatment-related effects on pup weight, sex distribution, or survival were noted
      for pups of either generation. Upon postmortem examination, no treatment-related
      gross lesions were observed in either the F0 or F1 parental animals or their
      weanlings. Histopathologic examination of reproductive tissues and pituitary
      glands from high-dose F0 and F1 parental animals did not reveal any changes
      related to treatment with HQ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253296
TI  - The effect of pretreatment on the biliary excretion of 2,3,7,8-tetrachlorodibenzo
      p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 3,3',4,4'-tetrachlorobiphenyl in
      the rat.
AB  - The laterally halogenated chemicals 2,3,7,8-tetrachlorodibenzofuran (TCDF) and
      3,3',4,4'-tetrachlorobiphenyl (TCB) exhibit the same spectrum of toxic effects as
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the prototype and most toxic member
      of the halogenated aromatic hydrocarbon family. Metabolism of all three compounds
      appears to be the rate-limiting step for excretion, which is primarily via the
      bile into the feces. Therefore, the biliary elimination of TCDF, TCDD, and TCB
      was examined as an indirect measure of metabolism. Male F344 rats were
      anesthetized with pentobarbital, the bile duct was cannulated, and 0.1 mumol
      [3H]TCDD, [14C]TCDF, or [14C]TCB/kg body wt was administered iv. Bile was
      collected for 0-8 hr while the animals were kept under anesthesia. To determine
      if TCDF was able to induce its own metabolism in vivo, a single dose of 1.0 mumol
      TCDF/kg was administered to rats by oral gavage 3 days prior to iv injection of
      0.1 or 0.3 mumol [14C]TCDF/kg. Biliary excretion and hepatic concentrations of
      [14C]TCDF were significantly increased in the pretreated animals. These results
      suggest an autoinduction of TCDF metabolism. Essentially all biliary [14C]TCDF
      radioactivity was attributable to metabolites. High-pressure liquid
      chromatography profiles of biliary radioactivity from 0 to 4 hr were
      qualitatively different between naive and pretreated rats. To determine if
      pretreatment with TCDD altered the metabolism of TCDF and vice versa, a single
      dose of 1.0 mumol TCDF/kg or 0.1 mumol TCDD/kg was administered by oral gavage 3
      days prior to iv injection of 0.1 mumol [3H]TCDD or [14C]TCDF/kg,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253297
TI  - Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to
      2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - The incidence of the reproductive disease endometriosis was determined in a
      colony of rhesus monkeys chronically exposed to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD or dioxin) for a period of 4 years. Ten years after termination of
      dioxin treatment, the presence of endometriosis was documented by surgical
      laparoscopy and the severity of disease was assessed. The incidence of
      endometriosis was directly correlated with dioxin exposure and the severity of
      disease was dependent upon the dose administered (p < 0.001). Three of 7 animals
      exposed to 5 ppt dioxin (43%) and 5 of 7 animals exposed to 25 ppt dioxin (71%)
      had moderate to severe endometriosis. In contrast, the frequency of disease in
      the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus
      monkeys housed at The Harlow Primate Center with no dioxin exposure. This 15-year
      study indicates that latent female reproductive abnormalities may be associated
      with dioxin exposure in the rhesus. Therefore, the effects of this toxin may be
      more diverse than previously recognized.

PMID- 8253298
TI  - Comparative carcinogenicity of polybrominated biphenyls with or without perinatal
      exposure in rats and mice.
AB  - Chronic toxicity and carcinogenicity studies of a polybrominated biphenyl mixture
      (PBB) were conducted in F344/N rats and B6C3F1 mice of each sex. The major
      objective of the study was to determine if exposure to PBB during the perinatal
      period, in addition to conventional exposure of animals for 2 years, enhances the
      sensitivity of the bioassay to identify the carcinogenic potential of this
      chemical. The studies were designed to determine the toxic and carcinogenic
      effects of dietary PBB in rats and mice receiving (i) perinatal exposure up to 8
      weeks of age followed by control diet for 2 years, (ii) exposure for 2 years
      beginning at the age of 8 weeks, and (iii) combined perinatal/adult exposure to
      PBB (perinatal exposure to 8 weeks of age followed by adult exposure for 2
      years). During the perinatal period, rats were exposed to PBB at dose levels
      ranging from 1 to 10 ppm and adult exposure concentrations ranged from 3 to 30
      ppm in the diet. In the mice, the dose levels ranged from 3 to 30 ppm in both
      perinatal and adult exposure portions of the chronic studies. A total of eight
      dose groups (including controls) were used with 60 animals in each group. Liver
      was the major target organ of PBB toxicity. Perinatal exposure alone (through
      dietary administration of 10 ppm PBB to the dams) had no effect on the incidences
      of neoplasms in female F344/N rats, but in male rats, perinatal exposure was
      associated with a marginally increased incidence of hepatocellular adenomas that
      may have been related to chemical administration. In male and female B6C3F1 mice,
      perinatal exposure to 30 ppm PBB resulted in significantly increased incidences
      of hepatocellular neoplasms. In adult-only dietary exposure studies, PBB was
      carcinogenic in male and female F344/N rats and male and female B6C3F1 mice based
      on increased incidences of hepatocellular neoplasms. Combined perinatal and adult
      dietary exposure to PBB confirmed the findings of the adult-only exposures for
      the increased incidences of hepatocellular neoplasms in rats and mice. In male
      rats, there were no enhancing effects of combined perinatal and adult exposure.
      However, perinatal exposure enhanced the susceptibility of female rats receiving
      adult exposure of 10 or 30 ppm to the induction of liver neoplasms. For male and
      female rats, a combined analysis of the incidences of leukemia in the adult-only,
      perinatal-only, and combined perinatal and adult exposure groups revealed an
      apparent association between increasing incidences of mononuclear cell leukemia
      and exposure to PBB.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8253299
TI  - Subchronic toxicity of cupric sulfate administered in drinking water and feed to
      rats and mice.
AB  - The effects of acute poisoning by cupric sulfate in a number of species are well
      known; however, the effects of chronic low-level ingestion of cupric sulfate are
      less well characterized. Because exposure of humans to cupric sulfate may occur
      through drinking water, food, soil, or ambient air, subchronic toxicity studies
      were conducted in male and female F344/N rats and B6C3F1 mice by the drinking
      water (2-week exposure) and dosed feed (2- and 13-week exposure) routes. Animals
      were evaluated for histopathology, clinical pathology, reproductive toxicity, and
      tissue metal accumulation, and target organs were examined by a variety of
      special stains and by electron microscopy to characterize the observed lesions.
      In drinking water, cupric sulfate concentrations of 300 to 100 ppm produced no
      ill effects, whereas concentrations of 3000 to 30,000 ppm were lethal to rats and
      mice within 2 weeks. In feed, cupric sulfate concentrations of 4000 to 16,000 ppm
      caused significant reductions in body weight gain in both species in the 2- and
      13-week studies. Hyperplasia and hyperkeratosis of the limiting ridge of the
      forestomach were present in both species in the 2- and 13-week studies. Rats in
      the dosed feed studies had a dose-related increase in inflammation in the liver
      and changes in clinical chemistry parameters which were indicative of
      hepatocellular damage and cholestasis. Histologic changes in the kidneys of rats
      consisted of a dose-related increase in the number and size of eosinophilic
      protein droplets in the epithelial cytoplasm and the lumina of the proximal
      convoluted tubules. Droplets were larger and more numerous in males than in
      females. Urinalysis results were suggestive of renal tubular epithelial damage.
      Iron staining of spleens from treated animals indicated a marked depletion of
      iron stores in both male and female rats, but not in mice, while hematologic and
      clinical chemistry alterations in rats in the 13-week study, along with
      histologic changes in bone in the 2-week dosed feed study, were indicative of a
      microcytic anemia. Cupric sulfate produced no adverse effects on any of the
      reproductive parameters measured in rats or mice of either sex. These results
      indicate that cupric sulfate at high exposure levels is a hepatic and renal
      toxicant, as well as an inducer of anemia in rodents, with rats more sensitive
      than mice following subchronic exposure.

PMID- 8253300
TI  - Assessing the neurotoxic potential of methyl ethyl ketoxime in rats.
AB  - The potential of methyl ethyl ketoxime (MEKO) to produce neurotoxicity following
      acute and subchronic exposure was studied in rats. A Functional Observational
      Battery, assessment of motor activity, and neuropathology evaluations were
      conducted in the context of acute and subchronic toxicity studies. Three
      independent studies are reported: a pilot time-effect study designed to determine
      the time course and time to peak effect following a single high dose of MEKO, a
      single-dose neurotoxicity study, and a subchronic (13-week) repeated-dose
      neurotoxicity study in rats. An acrylamide-positive control group was included in
      the acute and subchronic studies for comparison with MEKO. Following an acute
      oral exposure of MEKO at a dose level of 900 mg/kg, locomotor activity was
      decreased compared to control with maximum decreases occurring between 30 and 60
      min following oral administration. In the acute study, transient treatment
      related changes in ease of cage removal, ease of handling, and in posture and
      gait were observed 1 hr after dosing with 900 mg/kg MEKO, as were significant
      depressions in motor activity. Following a single 300 mg/kg dose, transient MEKO
      related changes in gait and aerial righting reflex were noted 1 hr after dosing.
      All effects were reversible within 24 hr of dosing. The single 100 mg/kg dose of
      MEKO was without observable effects. No acrylamide-related behavioral effects
      were noted following a single 50 mg/kg dose. In the subchronic study, transient
      treatment-related changes in ease of cage removal, ease of handling, and in
      posture, gait, and aerial righting were observed at the 400 mg/kg/day dose level
      when assessments were conducted immediately after dose administration. No
      consistent behavioral effects were observed prior to daily dose administration
      even after 13 weeks of exposure, indicating a lack of cumulative behavioral
      effect. No consistent behavioral changes were noted at doses of 125 mg/kg/day and
      below. Significant dose-related decreases in red cell mass, and increases in
      methemoglobin levels, reticulocyte, leukocyte, Heinz body counts, and spleen
      weights occurred at subchronic MEKO doses of 40 mg/kg/day and higher. No MEKO
      related neuropathological changes occurred. Animals receiving acrylamide at 20
      mg/kg/day showed expected behavioral and neuropathological changes consistent
      with peripheral neuropathy. In conclusion, high doses of MEKO can produce
      transient and reversible changes in neurobehavioral function consistent with
      central nervous system (CNS) depression. No evidence of cumulative neurotoxicity
      was detected. The hematopoietic system was effected at doses which did not
      produce detectable changes in CNS function.

PMID- 8253301
TI  - Effect of dose on the disposition of 2-ethoxyethanol after inhalation by F344/N
      rats.
AB  - Glycol ethers such as 2-ethoxyethanol (EE) are widely used as solvents because
      they are miscible in aqueous and organic solutions. Toxic effects of EE in
      rodents include teratogenicity, fetotoxicity, hematotoxicity, and testicular
      atrophy. The purpose of this study was to determine the effect of dose on the
      absorption, metabolism, and excretion of 2-ethoxy [U-14C]ethanol by F344/N rats
      after inhalation exposure. Rats were exposed to either 5 ppm EE for 5 hr 40 min
      or 46 ppm EE for 6 hr. The uptake and metabolism of EE were linear in the
      concentration range studied. Significant percentages of the retained doses were
      exhaled during (22%) and after exposure (16%) as 14CO2. Forty-six percent of the
      retained dose was excreted in the urine. Approximately 10% of the retained dose
      was detected in the carcass 66 hr after exposure. The major urinary metabolite
      was ethoxyacetic acid (EAA), the toxic metabolite of EE. The amount of EAA
      excreted was linearly related to exposure concentration. Ethylene glycol and N
      ethoxyacetyl glycinate were identified as minor metabolites excreted in the
      urine. The results of this study suggest that the toxicity of inhaled EE should
      be directly proportional to the exposure concentration up to 46 ppm if the
      toxicity of EE is due to EAA.

PMID- 8253302
TI  - Evaluation of the relationship between PAH content and mutagenic activity of
      fumes from roofing and paving asphalts and coal tar pitch.
AB  - Fume condensates from asphalt and coal tar pitch were evaluated to determine if
      polycyclic aromatic hydrocarbon (PAH) composition, crude oil source, or
      temperature at which the fume was generated correlated with mutagenic activity.
      The fume condensates were tested for mutagenic activity using a modified Ames
      Test. Benzo[a]pyrene (BP) and other PAHs were detected in all samples. The
      concentration of BP in coal tar pitch was 18,100 ppm while the concentration in
      asphalt was less than 6 ppm. Coal tar fumes contained between two and three
      orders of magnitude more BP, as well as other PAH species, than asphalt fumes.
      Coal tar fume condensates were also approximately 100 times more mutagenic than
      those of asphalt. Generation temperature, crude oil source, and/or process
      conditions affected the PAH concentrations but not the mutagenicity in roofing
      asphalt fume condensates. With paving asphalt fumes, PAH content and mutagenicity
      varied with crude oil source but not with processing conditions; due to limited
      data, it was not possible to determine the effect of generation temperature. Coal
      tar pitch fumes generated at 316 degrees C contained significantly higher
      concentrations of PAHs than those generated at 232 degrees C and the mutagenic
      activity generally paralleled the PAH content. A subset of the paving asphalts
      demonstrated good correlation between mutagenicity and three- to seven-ring PAH
      content. These results indicate that asphalt fumes are far less mutagenic than
      coal tar fumes. Asphalt fumes differ in their ability to induce mutagenic
      activity, and, most likely, in their potential carcinogenicity.

PMID- 8253303
TI  - Phase-specific developmental toxicity in mice following maternal methanol
      inhalation.
AB  - Methanol is toxic to embryos of mice and rats when inhaled by dams at high
      concentrations. The present studies examined methanol-induced developmental
      toxicity following inhalation exposure (6 hr/day) of pregnant CD-1 mice to 5000,
      10,000 or 15,000 ppm either throughout organogenesis (GD 6-15), during the period
      of neural tube development and closure (GD 7-9), or during a time of potential
      neural tube reopening (GD 9-11). Transient neurologic signs and reduced body
      weights were observed in up to 20% of dams exposed to 15,000 ppm. Examination of
      near-term fetuses revealed embryotoxicity (increased resorptions, reduced fetal
      weights, and/or fetal malformations) at 10,000 and 15,000 ppm, while 3-day
      exposures at 5000 ppm yielded no observable adverse effects. Terata included
      neural and ocular defects, cleft palate, hydronephrosis, deformed tails, and limb
      (paw and digit) anomalies. Neural tube defects and ocular lesions occurred after
      methanol inhalation between GD 7-9, while limb anomalies were induced only during
      GD 9-11; cleft palate and hydronephrosis were observed after exposure during
      either period. These findings were consistent with prior reports that maternal
      methanol inhalation at high levels induces developmental toxicity in a
      concentration-dependent manner. Furthermore, our data indicate that the spectrum
      of teratogenic effects depended upon both the timing (i.e., stage of embryonic
      development) and the number of methanol exposures.

PMID- 8253304
TI  - Food restriction during organogenesis in rabbits: effects on reproduction and the
      offspring.
AB  - To assess the effects of markedly restricted food intake versus ad libitum
      feeding or a slightly restricted feeding regimen during the period of
      organogenesis we fed groups of 16-18 pregnant rabbits Purina Certified High Fiber
      Chow ad libitum, 150 g/day, 75 g/day, or 15 g/day on Gestation Days 6 to 18
      inclusive. Prior to and after organogenesis the animals were provided food ad
      libitum (ad lib). Clinical observations, body weights, and food and water
      consumption were recorded daily. On Gestation Day 30 each doe was euthanatized
      and necropsied, and maternal and fetal data were collected. Each fetus was
      examined for external, visceral, and skeletal variations and malformations.
      Ossification parameters were also evaluated. Statistical analyses were conducted
      in two ways, first comparing the restricted groups to the ad lib group and second
      comparing the 15 and 75 g/day groups to the 150 g/day group. During Days 6-18,
      the 15 and 75 g/day groups had significantly decreased weight gain (actual weight
      loss), compared to the groups fed 150 g/day or ad lib. Water consumption was also
      significantly decreased in the 15 g/day group during this period, compared to the
      ad lib group. When food was provided ad lib on Days 19-30 to the restricted
      groups, weight gain was significantly higher in the 15 and 75 g/day groups than
      the group previously given 150 g/day and the ad lib group. There were no
      differences in water consumption during that period. Abortion occurred in three
      15 g/day animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253305
TI  - Tissue distribution and toxicokinetics of 2,3,7,8-tetrachlorodibenzo-p-dioxin in
      rats after intravenous injection.
AB  - Male Sprague-Dawley rats (240-290 g) received intravenously a nonlethal (9.25
      micrograms/kg) or a lethal (72.7 micrograms/kg) dose of 14C-labeled 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) administered as an emulsion. Animals were
      euthanized between 5 min and 16 days (lethal dose) or 32 days (nonlethal dose)
      after treatment. Tissue distribution was considered complete after 24 hr, as by
      this time radioactivity levels in white adipose tissue had reached a maximum. The
      highest levels of radioactivity were found in liver (5% of dose/g tissue),
      followed by white fat (1% of dose/g tissue); serum was lowest at 0.01% of dose/ml
      serum. Relatively high levels of radioactivity were also detected in most known
      target organs of TCDD toxicity, e.g., brown fat, adrenals, and thyroid. The
      pattern of organ distribution of TCDD was essentially the same after the lethal
      and the nonlethal dose, but did not follow a simple lipophilicity relationship,
      as levels in liver were higher than those in white fat, and those in brain were
      extremely low. A pool of TCDD in liposomes initially trapped in lung and spleen
      was redistributed within 24 hr mainly to liver and adipose tissue. Affinity of
      TCDD to storage fat seemed to play a more important role as a driving force for
      redistribution than did induction of cytochrome P450 1A2. The terminal slope of
      elimination of TCDD from tissues indicated a half-life of 16 days after the
      nonlethal dose. After the lethal dose radioactivity declined in all tissues for 2
      to 8 days and then increased again, reflecting shrinking tissue volumes as well
      as remobilization of TCDD caused by the process of body mass wasting.
      Distribution data for 17 tissues and serum were subjected to regression analysis
      and resulted in up to two uptake phases and up to three elimination phases for a
      given tissue. After the nonlethal dose TCDD was mainly excreted via feces;
      combined urinary and fecal excretions occurred with a biological half-life of
      16.3 +/- 3.0 days. Much longer half-lives were detected in white fat and skin.
      After the lethal dose, the fecal excretion of TCDD-derived radioactivity
      decreased after 8 days, and urinary excretion increased starting 12 days after
      dosing. Radioactivity in liver and white fat and the extractable portion in feces
      was mainly unchanged TCDD, as determined by thin-layer chromatography.
      Radioactivity in urine indicated the presence of a metabolite(s) of TCDD only.

PMID- 8253306
TI  - Comparative effects of immunotoxic chemicals on in vitro proliferative responses
      of human and rodent lymphocytes.
AB  - In order to determine the comparability of human and rodent in vitro systems, the
      direct effects of various therapeutic or environmental chemicals on proliferative
      responses of lymphocytes of mouse, rat, and human origins were examined and
      analyzed by a detailed statistical approach. Four compounds of diverse structure
      and mechanism of action which are known to impair lymphocyte transformation, such
      as hydroquinone, T-2 toxin, lead nitrate, as well as the widely used
      immunosuppressive drug cyclosporin A, were chosen as model test substances. T
      cells were stimulated by phytohaemagglutinin as well as monoclonal antibodies
      directed at the T cell receptor/CD3 complex, while B cells were activated by the
      T-independent mitogens, including Staphylococcus aureus cells, Escherichia coli
      lipopolysaccharide, and Salmonella typhimurium mitogen with specificity for
      human, mouse, and rat lymphocytes, respectively. In almost all cases the
      chemicals altered lymphoproliferative responses in a concentration-related manner
      in all three species. In general, overall similarities in the relative
      sensitivity of lymphoblastogenesis were obtained when the human dose-response
      curves were compared to the rodent response curves. Frequent, statistically
      significant species-dependent discrepancies of the overall response curves
      between mice and rats were observed. Large, statistically significant differences
      were observed for inorganic lead, revealing obvious divergences of the effect
      patterns in all cases, across all species. In this case, rodent species,
      especially the rat, were very sensitive to immunomodulation by lead, whereas
      human cells were relatively resistant. It is suggested that direct interspecies
      comparisons of immunological effects due to chemical treatment in vitro can
      provide a greater understanding of the relationship between animal and human
      data, which will improve the confidence of extrapolation from findings in
      laboratory animals to human health risk.

PMID- 8253307
TI  - [Acute pancreatitis: is early prognostic evaluation reliable?].

PMID- 8253308
TI  - [Follicular gastritis in adults. Relations with Helicobacter pylori, histological
      and endoscopic aspects].
AB  - Follicular gastritis (FG) is characterized by lymphoid follicle hyperplasia in
      the gastric mucosa. The aim of this prospective study was to determine the
      prevalence of FG in adults, their relation to Helicobacter pylori infection, and
      their histological and endoscopic features. Of 445 patients (379 men, 66 women),
      36.4 years old (range: 18-86), FG was detected in 63 patients (14.2%). This was
      highly significantly associated with H. pylori infection: 49/138 infected
      patients (35.5%) versus 14/307 non infected patients (4.6%) (P < 0.001). None of
      the histological features of the antral mucosa were correlated with FG. The
      prevalence of FG in patients less than 20 years old (in 45.4%) and between 20 and
      40 years (in 41.3%) was higher than in patients aged from 40 to 60 years (in 33%)
      and older than 60 years (in 23%) (no significant difference). No one endoscopic
      feature of the gastric mucosa was predictive of the presence of FG. We conclude
      that FG is highly correlated with H. pylori infection and represents a local
      immune response to bacterial antigens. Their occurrence is probably
      multifactorial and related to age, duration of infection, bacterial strains, host
      immune status.

PMID- 8253309
TI  - [Vital prognosis in acute pancreatitis. Study of 5 clinicobiological indices].
AB  - The values of the Acute Physiology and Chronic Health Enquiry (Apache II) and the
      Simplified Acute Physiology Scores (SAPS) were compared with Ranson and Imrie
      scores to predict death after acute pancreatitis. Fifty-five (ten deaths)
      patients were evaluated. Patients who died had a mean score greater than those
      who survived. The accuracy of all scores was similar after 48 hours. The ICU
      (Intensive Care Unit) available at the time of admission may facilitate the early
      selection of patients for appropriate management.

PMID- 8253310
TI  - [Clinical characteristics and evolution of permanent digestive ostomies. Results
      of a nation-wide retrospective survey].
AB  - Factors influencing the achievement and the evolution of permanent stomas were
      determined during a National Inquiry including 1,082 stomas (978 colostomies and
      104 ileostomies). This study, although not exhaustive, was representative, giving
      its statistical value. The principal concepts are well known with regard to the
      indications of colostomies (cancer) and ileostomies (inflammatory bowel
      diseases), to age (older in patients with colostomies: 63.8 vs 41.7 years, P <
      0.001) and to the unequal geographical distribution of ileostomies (most frequent
      in northern provinces: P = 0.02). Frequency of complications (25%) after
      definitive stoma have decreased since 1985 (P = 0.01) but reoperation was
      necessary in 50% of cases. Most patients were informed of their stoma before the
      operation, but 23% were not. Among the informed patients, one fourth considered
      themselves insufficiently acquainted with their stoma.

PMID- 8253311
TI  - [Consequences and undesirable effects of non steroidal anti-inflammatory agents
      on the intestine. 2: Effects of NSAID on the small intestine and the colon].

PMID- 8253312
TI  - [Are prognostic factors of hepatocellular carcinoma known?].

PMID- 8253313
TI  - [Prognostic factors of hepatocellular carcinoma. Multifactorial analysis of 84
      cases].
AB  - To identify prognostic factors taking in account recent advances in diagnosis and
      treatment, 24 clinical, biological, and morphological factors were evaluated by
      means of uni- and multivariate analysis in 84 patients with hepatocellular
      carcinoma diagnosed between 1984 and 1991. Okuda's grading (P < 0.01),
      creatininemia (P < 0.01), and treatment (P < 0.05) were independent prognostic
      factors. Des-gamma-carboxyprothrombin reached a significant level (P < 0.05) in a
      subgroup of 32 recent patients but its prognostic value needs to be confirmed.
      Further prospective randomized trials comparing surgical and non-surgical
      treatment should take these factors into account.

PMID- 8253314
TI  - [Comparison of six potential serum markers of hepatic fibrosis in alcoholic
      disease of the liver].
AB  - The aim of this study was to compare 6 potential serum markers for hepatic
      fibrosis in patients with alcoholic liver disease. Ninety-three patients (50 +/-
      11 years old, 62 males) with biopsy-proven alcoholic liver disease were included
      in the study. A liver biopsy and serum assays of type I, type III and type IV
      collagens, N-terminal peptide of type III procollagen, laminin (by
      radioimmunoassays) and apolipoprotein A1 (by nephelometry) were performed in all
      patients. A histological score of hepatic fibrosis was established. Alcoholic
      hepatitis lesions and perisinusoidal fibrosis were assessed separately. A
      significant correlation was found between the score of hepatic fibrosis and serum
      levels of type I collagen (r = 0.44, P < 10(-3)), type III collagen (r = 0.36, P
      < 10(-2)), N-terminal peptide of type III procollagen (r = 0.50, P < 10(-3)),
      type IV collagen (r = 0.44, P < 10(-3)), laminin (r = 0.50, P < 10(-3)), and
      apolipoprotein A1 (r = 0.21, P < 0.05). After adjustment for the presence of
      lesions of alcoholic hepatitis and perisinusoidal fibrosis (partial correlation),
      serum levels of type I collagen, type III collagen, N-terminal peptide of type
      III procollagen, type IV collagen, and laminin remained significantly correlated
      with the score of hepatic fibrosis; in contrast, correlation with serum
      apolipoprotein A1 was no longer significant. Serum levels of N-terminal peptide
      of type III procollagen, type IV collagen and laminin were significantly higher
      in patients with perisinusoidal fibrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253315
TI  - [Reversal of portal blood flow in cirrhosis. Clinical, endoscopic and ultrasound
      endoscopic correlations in 72 patients].
AB  - From January to December 1991, the portal venous system was evaluated by Doppler
      ultrasonography in 72 patients with liver cirrhosis. The objectives of this study
      were to evaluate the prevalence of spontaneous reversal of blood flow in the
      portal vein and to assess the relationship between Doppler ultrasound
      investigation and clinical, biochemical, endoscopic (70 patients), and
      endosonographic (44 patients) features. Reversed flow was quite frequent
      (alternating: 17%, permanent: 22%) and its prevalence did not differ in relation
      to age, sex, serum gammaglobulin concentration and Child-Pugh class. In patients
      with reversed portal venous flow, the prevalence of hepatic encephalopathy was
      higher (39% vs 13.5%, P < 0.05), but the prevalence of esophageal or gastric
      varices was not related to that pattern. Endosonography detected gastric wall
      abnormalities in a higher proportion of patients with reversed portal flow than
      in patients without it (P < 0.05). This study suggests that reversal of flow in
      the portal vein could play a role in the development of the gastric wall
      abnormalities in liver cirrhosis, which are detected by endosonography but not by
      endoscopy.

PMID- 8253316
TI  - [Protein metabolism, physical fitness, nutritional status and liver
      transplantation].

PMID- 8253317
TI  - [Cystic lymphangioma of the duodenum revealed by digestive hemorrhage and
      associated with exudative enteropathy].
AB  - Cystic lymphangioma is a rare and benign congenital lesion of the lymphatic
      system, which can become manifest at any age. Intra-abdominal cysts are found in
      less than 10% of cases and mesenteric involvement is the most common. The case of
      a patient with intra-abdominal cystic lymphangioma that involved the liver, the
      spleen, the kidney and the small intestine, and complicated by gastrointestinal
      bleeding and protein losing enteropathy is reported herein. Despite severe gastro
      intestinal manifestations, spontaneous outcome was favorable. This observation
      suggests that a) duodenal cystic lymphangioma must be considered as a cause of
      gastrointestinal bleeding and of protein losing enteropathy, b) conservative
      treatment can be proposed.

PMID- 8253318
TI  - [Autoimmune dysthyroidism induced by alpha interferon in two female patients with
      chronic non-A, non-B hepatitis].
AB  - We report two cases of autoimmune thyroid disorders which appeared after 6 months
      of recombinant alpha interferon therapy given for chronic non-A, non-B hepatitis.
      There was no family or personal history of thyroid disease, or had the patients
      taken any hepatic or thyroid toxic drugs. The other causes of hepatic and thyroid
      diseases were ruled out. The first case concerned a 33-year-old woman with
      sporadic hepatitis C. Therapy was complicated by the appearance of antimicrosomal
      thyroid antibodies and hypothyroidism. At 22 months, substitutive therapy was
      still necessary in one case. The second case involved a 37-year-old woman with
      post-transfusional non-A, non-B hepatitis which was complicated by transient
      hypothyroidism preceding thyrotoxicosis (with TSH-receptor antibodies). We
      observed a return to euthyroidism and loss of associated antibodies after
      withdrawal of interferon and institution of hormonal therapy.

PMID- 8253319
TI  - [Esophageal mycosis during treatment with omeprazole].

PMID- 8253320
TI  - [Menetrier disease associated with gastric linitis. Echoendoscopic aspects].

PMID- 8253321
TI  - [Malignant non-Hodgkin's ganglionary lymphoma and gastric adenocarcinoma].

PMID- 8253322
TI  - [Digestive hemorrhage in typhoid fever: value of surgical hemostasis].

PMID- 8253323
TI  - [Cardiac toxicity of 5 fluoro-uracil: a case of atrioventricular conduction
      disorders].

PMID- 8253324
TI  - [Hepatocellular carcinoma complicating primary sclerosing cholangitis].

PMID- 8253325
TI  - [Value of porta-hepatic shunt before colonic resection in a patient with
      cirrhosis].

PMID- 8253326
TI  - [False aneurysm of the hepatic artery revealed by hemobilia in Buerger disease:
      an incidental association?].

PMID- 8253327
TI  - [Chronic cirrhogenic hepatitis induced by germander].

PMID- 8253328
TI  - [Acute hepatic disorders after exposure to dimethylformamide. Clinical and
      histological aspects].

PMID- 8253329
TI  - [Chronic active cirrhogenic hepatitis induced by fenofibrate].

PMID- 8253330
TI  - [Thiophene-induced hepatitis: a new case].

PMID- 8253331
TI  - [Symptomatic hepatic disorders after ingestion of tenoxicam].

PMID- 8253332
TI  - [Alkaline reflux and peptic esophagitis: real or imagined?].

PMID- 8253333
TI  - [Ileoanal anastomosis with pouch: a rigorous surgical technique is necessary, but
      the most frequent long-term postoperative complication remains inflammation of
      the pouch].

PMID- 8253334
TI  - [Role of peripheral arterial vasodilation in the formation of ascites in patients
      with cirrhosis].

PMID- 8253335
TI  - The viability of the subspecialty of gastroenterology.

PMID- 8253336
TI  - Presentation of the Julius Friedenwald Medal to John S. Fordtran, M.D.

PMID- 8253337
TI  - Smoked drums, squiggles, and clinical science: motility in Gastroenterology, 1943
      1993.

PMID- 8253338
TI  - Bicarbonate secretion in rabbit ileum: electrogenicity, ion dependence, and
      effects of cyclic nucleotides.
AB  - BACKGROUND: Ileal HCO3- secretion is not well understood. The aim of this study
      was to examine its Na+ and Cl- dependencies, electrogenicity, and responses to
      amiloride, 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulfonate (SITS), and
      cyclic nucleotides. METHODS: The serosa to mucosa HCO3- flux (Jsm) across rabbit
      ileal mucosa mounted between HCO(3-)-free mucosal solution and HCO(3-)-containing
      serosal solutions was determined by titration. RESULTS: In SO4(2-)-containing
      Ringer's solution, Jsm varied with [Na+] in two phases, one with a high and one
      with a low affinity for Na+; amiloride inhibited the high- and SITS inhibited the
      low-affinity phase. Switching from SO4(2-)- to Cl(-)-containing Ringer's solution
      caused a SITS-inhibitable 42% increase in Jsm. Changes in Jsm were coupled 3:2
      with changes in short-circuit current. Cyclic nucleotide effects on Jsm were as
      follows. In SO4(2-)-containing Ringer's solution at 141 (but not 80) mmol/L Na+,
      theophylline caused equal increases in Jsm and short-circuit current that equaled
      the combined effects of 8-Br-5'-cyclic guanosine monophosphate (cGMP) and 8-Br-5'
      cyclic adenosine monophosphate (cAMP). Serosal SITS blocked these effects, but
      amiloride did not. In Cl(-)-containing Ringer's solution, theophylline and
      bumetanide together (but not separately) increased Jsm. CONCLUSIONS: (1)
      Basolateral HCO3- entry occurs via Na+/H exchange and a SITS-inhibitable process
      (Na(+)-HCO3- cotransport?). (2) Most HCO3- exit across the brush border occurs by
      a Cl(-)-independent process and some by Cl-/HCO3- exchange. (3) At low cellular
      [Cl-], HCO3- can be secreted via anion channels activated by cAMP and cGMP. (4)
      Ileal HCO3- secretion is electrogenic.

PMID- 8253339
TI  - Tissue-selective inhibition of prostaglandin synthesis in rat by tepoxalin: anti
      inflammatory without gastropathy?
AB  - BACKGROUND: Inhibition of prostaglandin synthesis is likely a primary mechanism
      for both the anti-inflammatory and ulcerogenic effects of nonsteroidal anti
      inflammatory drugs (NSAIDs). The present study examined the mechanism underlying
      the ability of a novel anti-inflammatory drug, tepoxalin, to suppress
      prostaglandin synthesis without inducing gastric mucosal injury. METHODS: The
      effects on prostaglandin synthesis by various tissues of tepoxalin, diclofenac,
      and indomethacin were examined in vivo and in vitro. These compounds were also
      studied in two inflammation models. The capacity of indomethacin and tepoxalin to
      induced antral ulceration in the rabbit was compared. RESULTS: In most tissues,
      tepoxalin was a weaker inhibitor of prostaglandin synthesis than the two NSAIDs.
      However, at a site of peripheral inflammation, tepoxalin was comparable with the
      NSAIDs in suppressing prostaglandin synthesis and in exerting anti-inflammatory
      effects. Indomethacin induced penetrating antral ulcers in rabbits whereas
      tepoxalin produced no detectable mucosal injury. CONCLUSIONS: The ability of
      tepoxalin to suppress inflammation without causing gastric mucosal injury appears
      to be related to its differential suppression of prostaglandin synthesis in
      various tissues. Compounds that selectively inhibit prostaglandin synthesis at
      sites of inflammation may represent a class of anti-inflammatory drugs without
      detrimental effects on the stomach.

PMID- 8253340
TI  - p53 protein accumulation in Barrett's metaplasia, dysplasia, and carcinoma: a
      follow-up study.
AB  - BACKGROUND: There is a significant interobserver and intraobserver variation in
      grading dysplasia in Barrett's metaplasia. New markers are needed to optimize the
      assessment of potential risk of cancer development in these patients. The aim of
      this study is to explore the use of p53 as a marker of neoplastic progression in
      Barrett's metaplasia. METHODS: Immunohistochemistry was used to study p53 protein
      accumulation in 114 specimens from 54 patients with Barrett's metaplasia.
      RESULTS: Positive staining was found in 0% of the cases negative for dysplasia,
      9% of those with low-grade dysplasia, 55% of those with high-grade dysplasia, and
      87% of those with adenocarcinoma. Follow-up was available on 24 patients. Two
      patients who showed low-grade dysplasia and who were positive for p53 on biopsy
      showed high-grade dysplasia in follow-up biopsies. Of 21 patients who had biopsy
      specimens negative of p53, only one showed high-grade dysplasia on subsequent
      biopsy specimens. CONCLUSIONS: Our data support the hypothesis that p53 plays an
      important role in the progression of Barrett's metaplasia to adenocarcinoma. The
      follow-up study indicates that positive immunostaining for p53 may be an
      objective marker of neoplastic progression in Barrett's metaplasia.

PMID- 8253341
TI  - Lactobacillus casei strain GG reverses increased intestinal permeability induced
      by cow milk in suckling rats.
AB  - BACKGROUND: Lactobacilli constitute a major part of the microflora throughout the
      gastrointestinal tract. This study aimed to investigate the effect of
      lactobacilli on the gut mucosal barrier. METHODS: Rat pups were divided into
      three experimental feeding groups at the age of 14 days. In addition to normal
      maternal milk, group "milk" received a daily gavage of cow milk, group "milk-GG"
      received Lactobacillus casei strain GG with cow milk, and controls were gavaged
      with the same volume of water. At 21 days, the absorption of horseradish
      peroxidase across patch-free jejunal segments and segments containing Peyer's
      patches was studied in Ussing chambers. RESULTS: The mean absorption of intact
      horseradish peroxidase expressed in ng.h-1.cm-2, was significantly different in
      the study groups in both patch-free segments (controls, 9 [95% confidence
      interval, 7-12]; milk, 72 [60-87]; and milk-GG, 15 [4-52]) and in segments
      containing Peyer's patches (controls, 3 [1-17]; milk, 80 [43-151]; and milk-GG,
      15 [4-56]). There was a significant increase in the frequency of cells secreting
      antibodies to beta-lactoglobulin (enzyme-linked immunospot assay) in the milk-GG
      group. CONCLUSIONS: Prolonged cow milk challenge in suckling rats increases gut
      permeability to intact proteins, whereas Lactobacillus GG counteracts this
      permeability disorder. The results suggest a link between the intensity of the
      antigen-specific immune response and stabilization of the mucosal barrier.

PMID- 8253342
TI  - Primary digestive tract lymphoma: a prospective multicentric study of 91
      patients. Groupe d'Etude des Lymphomes Digestifs.
AB  - BACKGROUND: The optimal management of primary gastrointestinal lymphoma including
      the use of surgery remains unsettled. This prospective study aimed to determine
      the prognostic factors of primary gastrointestinal lymphoma and to evaluate a
      therapeutic strategy based on surgical tumor reduction, followed by chemotherapy
      adapted to the histological type of tumor and tumor removal or nonremoval.
      METHODS: Ninety-one patients were included (mean age, 50.4 years) with mainly
      gastric (61%) or several digestive tract organ (18%) involved sites in clinical
      stages IE (43%), IIE (27%), and IV (30%). Three therapeutic groups were defined:
      group I, patients with low-grade lymphoma (n = 28); group II, patients with high
      grade lymphoma who had complete tumor removal (n = 24); and group III, patients
      with high-grade lymphoma who had only partial or no tumor removal (n = 39). Each
      group underwent adapted chemotherapy. RESULTS: The respective overall 5-year
      survival rates for groups I, II, and III were 81% +/- 6%, 100%, and 56% +/- 8%,
      respectively (P < 0.0001). By Cox multivariate analysis, the prognostic factors
      of survival were age under 65 (P < 0.05), gastric localization (P < 0.05), stage
      IE (P < 0.001), and radical or incomplete surgery (P < 0.01). CONCLUSIONS:
      Combined radical surgery and chemotherapy according to histological grading is
      associated with prolonged remission in patients with primary digestive tract
      lymphoma. Moreover, compared with chemotherapy alone, incomplete resection of
      tumor is associated with increased survival of high-grade lymphomas.

PMID- 8253343
TI  - Expression of bombesin-receptor subtypes and their differential regulation of
      colonic smooth muscle contraction.
AB  - BACKGROUND: Bombesin-related peptides show different potencies, suggesting the
      existence of at least two receptor subtypes. The aim of this study was to assess
      the relationship and contribution of each receptor subtype on smooth muscle
      contraction. METHODS: The expression of bombesin-receptor subtype messenger RNA
      (mRNA) was examined in human and rabbit smooth muscle from the rectosigmoid
      colon, and the contribution of each of the receptor subtypes to smooth muscle
      contraction was investigated by blocking mRNA translation of either neuromedin B
      or gastrin-releasing peptide (GRP) receptor subtype or of both. RESULTS:
      Neuromedin B and GRP receptor mRNAs were detected in human and rabbit colonic
      smooth muscle cells. Incubation with neuromedin B receptor antisense
      oligonucleotides inhibited the neuromedin B-induced contraction, whereas
      incubation with GRP receptor antisense oligonucleotides inhibited the GRP-induced
      contraction. Incubation with GRP plus neuromedin B receptor antisense
      oligonucleotides inhibited the contractile response induced by bombesin,
      neuromedin B, and GRP. CONCLUSIONS: Distinct neuromedin B and GRP receptor
      subtypes are present on smooth muscle cells of the rectosigmoid colon, and
      bombesin interacts with both neuromedin B and GRP receptors, resulting in a
      complex contraction that is sustained in nature.

PMID- 8253344
TI  - Peroxynitrite-induced rat colitis--a new model of colonic inflammation.
AB  - BACKGROUND: Excessive production of nitric oxide, characteristic of inflamed
      states, may have deleterious effects through its facile conversion (in the
      presence of O2) to peroxynitrite, which promotes lipid and sulfhydryl oxidation.
      This study assessed the effect of peroxynitrite on the rat colon. METHODS:
      Peroxynitrite was administered intrarectally to rats. One, 3, 7, and 21 days
      after treatment, a distal colonic segment was isolated and tissue was obtained
      for histological evaluation and determination of myeloperoxidase activity and
      NOX, and eicosanoids generation. RESULTS: Within 24 hours, the exposed segment
      was edematous and congested with occasional hemorrhagic mucosal ulceration. On
      day 7, the lumen was narrow; at day 21, there were signs of stenosis.
      Histological analysis showed transmucosal necrosis, acute inflammation, and
      exudative edema 24 hours after treatment. Surface re-epithelization and
      infiltration of granulation tissue were present at 1 week. Resolution of edema,
      mucin repletion, thickening of muscularis mucosa and propria, and fibrosis were
      observed at 3 weeks. Significant increase in NOX generation and myeloperoxidase
      and NO synthase activities were observed at 24 hours, whereas enhanced
      leukotriene generation was observed only at 21 days. CONCLUSIONS: Peroxynitrite
      induced colonic inflammation provides a novel model of NO-related tissue injury
      and offers the opportunity to further explore the potential role of NO in the
      pathogenesis of inflammatory bowel disease.

PMID- 8253345
TI  - Differential cytokine expression by human intestinal epithelial cell lines:
      regulated expression of interleukin 8.
AB  - BACKGROUND: To characterize the role of intestinal epithelial cells in mucosal
      host defense, we have examined constitutive cytokine expression and regulated
      expression of interleukin (IL)-8 by human colonic epithelial cells. METHODS:
      Cytokine expression by the human colonic epithelial cell lines, T84, Caco-2,
      SW620, and HT29 was assessed by using polymerase chain reaction amplification of
      reverse-transcribed RNA. Regulated IL-8 expression was analyzed by nuclear run
      off assays, Northern blot analysis, and enzyme-linked immunosorbent assay.
      RESULTS: The cell lines constitutively expressed messenger RNA (mRNA) for IL-8
      and transforming growth factor beta 1. In addition, some cell lines expressed
      mRNA for IL-1 alpha, IL-1 beta, IL-10 and tumor necrosis factor alpha (TNF
      alpha). None of the cell lines expressed mRNA for IL-2, IL-4, IL-5, IL-6, or
      interferon gamma. Cell lines secreted IL-8 either constitutively or after
      stimulation with the physiological agonists TNF alpha, IL-1 beta, or
      lipopolysaccharide. Increased IL-8 secretion after TNF alpha stimulation of T84
      cells was accompanied by increased IL-8 mRNA levels and an increased
      transcription rate of the IL-8 gene. IL-8 was preferentially secreted at the
      basolateral surface of polarized T84 cells. In further studies, freshly isolated
      human colon epithelial cells also secreted IL-8. CONCLUSIONS: These results
      support the notion of bidirectional communication between intestinal epithelial
      cells and mucosal immune and inflammatory cells.

PMID- 8253346
TI  - Demonstration of a phospholipid-rich zone in the human gastric epithelium damaged
      by Helicobacter pylori.
AB  - BACKGROUND: Recently, a hydrophobic layer has been shown by the contact angle
      method in human gastric biopsy specimens. The aim of this study was to show the
      existence of a phospholipid-rich layer in the human gastric epithelium and to
      investigate the influence of Helicobacter pylori on these structures. METHODS:
      Biopsy specimens from the gastric antrum were obtained during gastroscopy from
      patients with normal gastric mucosa as well as from patients with H. pylori
      positive gastritis for electron microscopical and histological examination.
      Structures reacting with a phospholipid-selective stain, iodoplatinate were
      analyzed by electron microscopy and electron-dispersive x-ray microanalysis.
      RESULTS: Both methods revealed the morphological existence of a phospholipid-rich
      zone covering the human gastric epithelial layer. Reaction products could be
      localized within the cells, at the epithelium closely associated with the
      surface, and in connection with the mucus. In infected tissue, H. pylori affects
      iodoplatinate-reactive material within the mucous layer and material covering the
      epithelium. CONCLUSIONS: The phospholipid-rich zone in the apical region of
      surface mucous cells is likely to represent an important factor of the gastric
      protective system in humans. The destruction of this hydrophobic layer may result
      in a reduction of hydrophobicity giving access to gastric acid.

PMID- 8253347
TI  - Gastric ammonia has a potent ulcerogenic action on the rat stomach.
AB  - BACKGROUND: The pathophysiological mechanism by which Helicobacter pylori induces
      mucosal injury has not been clarified. The aim of this study was to investigate
      the role of urea, urease, and ammonia in rat gastric mucosal lesions using an ex
      vivo chamber model. METHODS: Two groups of rats, normotensive rats and those
      subjected to ischemia, were studied. The gastric mucosa was examined
      histologically and macroscopically, and the transmucosal potential difference was
      measured. RESULTS: Instillation of urea into the stomach generated ammonia in the
      presence of urease. The amount of ammonia was increased depending on the
      concentration of urea and was closely associated with the severity of the
      histological lesions. The exposure of the stomach to 15-60 mmol/L ammonium
      hydroxide induced both a reduction in transmucosal potential difference and
      microscopic damage to the gastric mucosa in normotensive rats. Moreover, 15-60
      mmol/L ammonium hydroxide produced severe macroscopic gastric lesions in the rats
      subjected to ischemia. CONCLUSIONS: These results show that ammonia is
      deleterious to the gastric mucosa and suggest the importance of urea, urease, and
      ammonia in the pathophysiology of gastric diseases in H. pylori-infected
      patients.

PMID- 8253348
TI  - Intestinal cancer risk and mortality in patients with Crohn's disease.
AB  - BACKGROUND: It is important to know about mortality, risk of intestinal cancer,
      and surgical intervention as well as possible predictive factors for patients
      with Crohn's disease. These prognostic parameters were estimated by regular
      follow-up of a complete, regional incidence cohort of 373 patients. METHODS:
      Annual assessments of clinical conditions were the basis for statistical
      evaluation with life table analysis, calculations of relative risk, and lifetime
      cancer risk. RESULTS: Survival curves for the total group of patients with
      Crohn's disease and the background population did not differ. However, a subgroup
      of patients aged 20-29 years at diagnosis (P = 0.04) and a subgroup of patients
      with extensive small bowel disease (P = 0.03) showed slightly increased mortality
      within the first 5 years. Cancer in small and/or large bowel occurred in 3
      patients vs. an expected 1.8(P = NS). Small bowel cancer was found in 2 patients
      vs. the 0.04 expected (P = 0.001). Lifetime risk of intestinal cancer was 4.1%
      compared with 3.8% for the Danish population in general (P = NS). Probability of
      surgical resection within 15 years after diagnosis was 70%. The initial extent of
      disease significantly influenced the probability for resection, which was 78% in
      ileocecal enteritis and 44% in all other localizations within 5 years after
      diagnosis. CONCLUSIONS: The overall mortality and life-time risk of cancer in
      patients with Crohn's disease was not found increased, although the risk of rare
      small bowel cancer was significantly increased.

PMID- 8253349
TI  - Shiga-like toxin-producing Escherichia coli in Seattle children: a prospective
      study.
AB  - BACKGROUND: The frequency with which stools contain Shiga-like toxin producing
      Escherichia coli not belonging to serotype O157:H7 is unknown in the United
      States. The aim of this study was to determine the frequency with which these E.
      coli are present in stools from children from Seattle submitted for bacteriologic
      analysis. METHODS: 2225 coliform colonies from 445 stools submitted for bacterial
      culture from Seattle children were probed with the structural genes of Shiga-like
      toxins I and II in a 1-year prospective study. The adherence and actin
      aggregating characteristics of these E. coli were subsequently determined.
      RESULTS: Five (1.1%) patients had non-O157:H7 Shiga-like toxin producing E. coli,
      a rate of isolation higher than Shigella or Yersinia (0.2% each) but lower than
      Campylobacter (2.5%), E. coli O157:H7 (2.9%), or Salmonella (3.4%). Only one of
      the five patients had bloody diarrhea. None developed hemolytic uremic syndrome.
      All strains adhered in a localized pattern to, and induced actin aggregation in,
      HeLa cells, and produced a toxin that was lethal to Vero cells. CONCLUSIONS: Non
      O157:H7 Shiga-like toxin producing E. coli are present in stools submitted for
      bacterial culture in a North American childhood population. Their role in
      childhood diarrhea warrants better definition.

PMID- 8253350
TI  - Comparison of clearance and metabolism of infused cholecystokinins 8 and 58 in
      dogs.
AB  - BACKGROUND: Cholecystokinin (CCK) 58 is the predominant molecular form of CCK in
      canine and human intestine and circulating blood. There is no report on the
      metabolism and clearance rate of CCK-58. The aim of this study was to compare the
      in vivo half-life and metabolism of CCK-58 with that of synthetic CCK-8. METHODS:
      CCK-58 was purified from canine intestine by consecutive high-performance liquid
      chromatographic (HPLC) and fast protein liquid chromatographic steps. The
      peptides were given to 12 dogs as an intravenous (IV) bolus injection to
      determine the half-life of circulating CCK. Six dogs were given CCK-58 or CCK-8
      as a constant IV infusion to determine plasma clearance rates and stability in
      circulating blood. Circulating molecular forms of CCK were determined by
      radioimmunoassay after extraction of CCK from plasma and characterization by
      HPLC. RESULTS: The half-life of CCK-58 was 4.4 +/- 0.6 minutes compared with 1.3
      +/- 0.1 minutes for CCK-8. Less than 5% of CCK-58 could be detected as smaller
      forms during constant IV infusion. CONCLUSIONS: The longer half-life of CCK-58
      compared with CCK-8 and the minimal conversion into smaller forms during constant
      IV infusion are consistent with the finding that CCK-58 is not only the major
      stored form but also the circulating form of CCK after endogenous stimulation in
      dogs.

PMID- 8253351
TI  - Primary sensory nerves mediate in part the protective mesenteric hyperemia after
      intraduodenal acidification in rats.
AB  - BACKGROUND: The mechanism of intraduodenal HCl-induced mesenteric hyperemia is
      unknown. In anesthetized rats, the hypothesis that the primary sensory nerves
      mediate the intraduodenal HCl-induced protective mesenteric hyperemia was tested.
      METHODS: The hyperemic response in the superior mesenteric artery (SMA) and
      superficial villus damage after intraduodenal bolus administration of saline,
      0.03N, or 0.1N HCl were measured. These changes induced by 0.1N HCl after mucosal
      anesthesia (1% lidocaine) or afferent nerve ablation (125 mg/kg subcutaneous
      capsaicin) were evaluated. The duodenal villus damage induced by intraduodenal
      perfusion of 0.1N HCl after mucosal afferent nerve stimulation by intraduodenal
      capsaicin or afferent nerve ablation by subcutaneous capsaicin was examined.
      RESULTS: Intraduodenal bolus administration of HCl produced a dose-related
      increase in SMA blood flow and villus tip damage. The mesenteric hyperemia
      induced by 0.1N HCl was significantly reduced, but the villus tip damage was not
      altered by prior intraduodenal lidocaine or subcutaneous capsaicin. The deep
      duodenal villus damage produced by intraduodenal perfusion of 0.1N HCl was
      decreased by intraduodenal but increased by subcutaneous capsaicin. CONCLUSIONS:
      The capsaicin-sensitive afferent nerves mediate in part the HCl-induced
      mesenteric hyperemia. They protect against the deep but not the superficial
      duodenal villus damage induced by HCl.

PMID- 8253352
TI  - Duodenal morphology and intensity of infection in AIDS-related intestinal
      cryptosporidiosis.
AB  - BACKGROUND: The pathogenesis of intestinal cryptosporidiosis is not known.
      Previous studies have shown that the intensity of infection varies between
      patients. The hypothesis of this study is that intestinal injury is related to
      the intensity of infection. METHODS: The histological abnormalities associated
      with Cryptosporidium infection were evaluated in duodenal biopsy specimens from
      18 patients with acquired immunodeficiency syndrome-associated cryptosporidiosis.
      The intensity of Cryptosporidium infection was assessed histologically in all
      patients as the percentage of mucosa covered by organisms and by quantitation of
      oocyst excretion in the stools of 14 patients. RESULTS: Duodenal biopsy specimens
      from 13 patients (72%) showed normal villous architecture. In these patients, the
      inflammatory component of the lamina propria was either normal or moderately
      increased. This increase consisted mostly of lymphocytes and plasma cells. Five
      of 18 patients (28%) had flattening of the mucosa associated with a prominent
      neutrophilic infiltrate. The intensity of infection in patients with villous
      flattening as measured from biopsy specimens and stool was significantly higher
      than in those without flattening (92% vs. 12% mucosa occupied with organisms; 738
      x 10(3) vs. 199 x 10(3) oocyst/mL stool) (P < 0.004 in both cases). CONCLUSIONS:
      Most patients with intestinal Cryptosporidium infection had normal duodenal
      villous architecture. Severe duodenal morphological abnormalities, including
      flattening of the villi, were associated with high-intensity infections.

PMID- 8253354
TI  - T-cell receptor variable genes and genetic susceptibility to celiac disease: an
      association and linkage study.
AB  - BACKGROUND: Genetic susceptibility of celiac disease is primarily associated with
      a particular combination of and HLA-DQA1/DQB1 gene; however, this does not fully
      account for the genetic predisposition. Therefore, the aim of this study was to
      examine whether T-cell receptor (TCR) genes may be susceptibility genes in celiac
      disease. METHODS: HLA class II typing was performed by polymerase chain reaction
      amplification in combination with sequence-specific oligonucleotide
      hybridization. TCR alpha (TCRA), TCR gamma (TCRG), and TCR beta (TCRB) loci were
      investigated by restriction fragment length polymorphism analysis. RESULTS:
      Allelic frequencies of TCRA, TCRG, and TCRB variable genes were compared between
      patients with celiac disease (n = 53) and control patients (n = 67), and relative
      risk (RR) estimates were calculated. The RR was 1.67 for allele C1 at TCRA1, 3.35
      for allele D2 at TCRA2, 1.66 for allele B2 at TCRG, and 1.35 for allele B at
      TCRB, showing no significant association. Additionally, linkage analysis was
      performed in 23 families. The logarithm of odd scores for celiac disease vs. the
      TCR variable genes at TCRA, TCRG, and TCRB showed no significant linkage.
      CONCLUSIONS: These data suggest that the analyzed TCR variable gene segments V
      alpha 1.2, V gamma 11, and V beta 8 do not play a major role in susceptibility to
      celiac disease.

PMID- 8253353
TI  - Neoplastic progression of human and rat intestinal cell lines after transfer of
      the ras and polyoma middle T oncogenes.
AB  - BACKGROUND: Activation of the p21ras and pp60c-src oncoproteins occurred at high
      incidence in the early stage of human colorectal carcinogenesis. Our study aimed
      to investigate the role of these signal-transduction pathways in the process of
      initiation and promotion of the malignant phenotype in intestinal cells. METHODS:
      The human Ha-ras and the polyoma middle T (Py-MT) viral oncogenes were
      transferred into large T oncogene of simian virus 40 immortalized rat intestinal
      epithelial SLC-44 cells and human colonic adenocarcinoma Caco-2 cells. RESULTS:
      These transfers conferred the tumorigenic and invasive phenotypes on immortalized
      SLC-44 cells and potentiated the tumorigenicity of Caco-2 cells and markedly
      repressed the terminal differentiation of this cell line. In SLC-44T cells,
      induction of the invasive phenotype by the activated Ha-ras oncogene correlated
      with weak expression of E-cadherin and reduced accumulation of the transcripts
      encoding the basement membrane components alpha 1 (IV) collagen, nidogen, and
      BM40, which might result partly from the inactivation of the transforming growth
      factor beta signaling pathway. The down-regulation of the alpha 1 (IV) collagen
      messenger RNA in SLC-44T cells was not due to the protein kinase C-dependent
      pathways or the secretion of autocrine factor(s). CONCLUSIONS: These results
      suggest that the activation of the p21ras and Py-MT/pp60c-src oncogenic pathways
      are critical effectors at different stages of colorectal carcinogenesis and in
      Caco-2 cells interferes with the program of enterocyte differentiation.

PMID- 8253355
TI  - Regulation of intracellular pH in isolated periportal and perivenular rat
      hepatocytes.
AB  - BACKGROUND: Liver acinus shows a well-known metabolic zonation. The aim of this
      study was to investigate intracellular pH (pHi) regulation in isolated periportal
      (PP) and perivenular (PV) rat hepatocytes. METHODS: 2,7-bis(carboxyethyl)-5(6)
      carboxy-fluorescein was used as pH-sensitive dye. Hepatocyte subconfluent
      monolayers were acid-loaded by exposure to 20 mmol/L NH4Cl and alkali-loaded by
      reducing external CO2 and HCO3- at an external pH of 7.4. RESULTS: In the
      presence of HCO3-/CO2, (1) baseline pHi was higher in PP (7.25 +/- 0.018) than in
      PV hepatocytes (7.20 +/- 0.013) (P < 0.05); (2) pHi recovery from an acid load
      was 40% higher in PP than in PV hepatocytes (P < 0.02) and was inhibited by
      amiloride by 36% in PV and 7% in PP hepatocytes; (3) DIDS inhibited amiloride
      independent pHi recovery from an acid load by 65% in PP and 52% in PV cells. In
      the absence of HCO3-/CO2, baseline pHi and pHi recovery from an acid load were
      not significantly different in PP and PV hepatocytes. pHi recovery from an alkali
      load was 30% higher in PV than in PP cells (P < 0.02). CONCLUSIONS: Our data
      suggest that isolated PP rat hepatocytes show higher activity for Na(+)-HCO3-
      cotransport, whereas PV cells show greater activity for Cl-/HCO3- exchanger.

PMID- 8253356
TI  - Phytosterolemia in children with parenteral nutrition-associated cholestatic
      liver disease.
AB  - BACKGROUND: Lipid emulsions used for parenteral nutrition (PN) contain
      phytosterols. Our hypothesis was that these phytosterols can accumulate and
      contribute to cholestatic liver disease and other complications of PN, e.g.,
      thrombocytopenia (which occurs in hereditary phytosterolemia). METHODS: Using gas
      chromatography-mass spectrometry, plasma concentrations of sterols were measured
      in 29 children aged 2 months to 9 years receiving PN and in 29 age-matched
      controls. The children receiving PN fell into two subgroups: 5 with severe PN
      associated cholestatic liver disease (bilirubin level, > 100 mumol/L; aspartate
      aminotransferase [AST] level, > 200 U/L) and 24 with a bilirubin level of < 100
      mumol/L and/or AST level of < 200 U/L. RESULTS: The 5 children with severe PN
      associated liver disease had plasma concentrations of phytosterols and sitostanol
      that were as high as those seen in patients with hereditary phytosterolemia
      (total phytosterols 1.3-1.8 mmol/L). All 5 had intermittent thrombocytopenia. A
      reduction in intake of lipid emulsion to < 50 mL.kg-1.wk-1 was associated with a
      decrease in plasma phytosterol concentrations and an improvement in liver
      function tests and platelet counts in two patients. Children with less severe PN
      associated liver disease had lower plasma phytosterol concentrations than the 5
      with severe disease. CONCLUSIONS: Children receiving PN who have high plasma
      phytosterol concentrations also have cholestatic liver disease and
      thrombocytopenia; phytosterolemia might contribute to the pathogenesis of
      complications of PN.

PMID- 8253357
TI  - Alterations in hepatocyte lysosomes in experimental hepatic copper overload in
      rats.
AB  - BACKGROUND: Although Wilson's disease is characterized by an accumulation of
      copper within hepatocyte lysosomes, the effects of excess copper on hepatic
      lysosomes are unknown. We studied the effects of excess copper on the structure,
      physicochemical properties, and pH of hepatocyte lysosomes using a rodent model.
      METHODS: Rats were copper loaded with 0.125% copper acetate in water for 6 weeks.
      Copper was measured by atomic absorption spectrophotometry. Morphology was
      studied by electron microscopy. Lysosomal membrane fluidity was studied by
      fluorescence polarization, and lipid composition was determined by gas
      chromatography. Hepatocyte lysosomal pH was determined by flow cytometry.
      RESULTS: Copper overload resulted in a 10-fold increase in hepatic copper.
      Hepatocyte lysosomes were enlarged and abnormally shaped with a 27-fold increase
      in copper, increased in vitro fragility, and decreased lysosomal membrane
      fluidity. Thiobarbituric acid reactive substances, a measure of lipid
      peroxidation, doubled in isolated lysosomal membranes. Polyunsaturated fatty
      acids increased, saturated fatty acids decreased, and membrane content of
      selected fatty acids was modified after copper overload. Lysosomal pH increased
      from 4.67 +/- 0.02 to 4.87 +/- 0.02. CONCLUSIONS: Copper overload causes
      alterations in lysosomal morphology, increases lysosomal fragility, decreases
      membrane fluidity, alters membrane fatty acid composition, and increases
      lysosomal pH. Copper catalyzed lipid peroxidation represents the likely mechanism
      for these alterations.

PMID- 8253358
TI  - Sensitivity, specificity, and predictability of biopsy interpretations in chronic
      hepatitis.
AB  - BACKGROUND: To determine the frequency of individual histological findings in
      different types of chronic hepatitis and to assess the sensitivity, specificity,
      and predictability of histological patterns in distinguishing these types, liver
      biopsy specimens were examined from 86 patients with autoimmune hepatitis (43
      patients), chronic hepatitis B (11 patients), chronic hepatitis C (21 patients),
      and cryptogenic hepatitis (11 patients). METHODS: Specimens were examined under
      code by a single hepatopathologist, and predefined histological features were
      sought. A histological diagnosis was rendered based on composite changes.
      RESULTS: Patients with chronic hepatitis C had a higher frequency of portal
      lymphoid aggregates (76% vs. 42%, P = 0.02) and steatosis (52% vs. 16%, P =
      0.006) than patients with autoimmune hepatitis, whereas the latter patients more
      commonly had severe periportal hepatitis (23% vs. 0%, P = 0.02), moderate to
      severe plasma cell infiltration of the portal tracts (66% vs. 21%, P = 0.005),
      and lobular hepatitis (47% vs. 16%, P = 0.04). Patients with chronic hepatitis B
      had a higher frequency of ground-glass hepatocytes (36% vs. 0%, P = 0.001) and
      multinucleated giant cells (54% vs. 2%, P = 0.0001) than those with autoimmune
      hepatitis and chronic hepatitis C. The histological diagnoses for these clinical
      entities had high specificity (81%-99%) and predictability (62%-91%) but low
      sensitivity (36%-57%). CONCLUSIONS: Autoimmune hepatitis, chronic hepatitis B,
      and chronic hepatitis C have characteristic individual histological features.
      Histological patterns based on these features have high specificity and
      predictability but low sensitivity.

PMID- 8253359
TI  - Long-term follow-up of chronic hepatitis B patients treated with interferon alfa.
AB  - BACKGROUND: There is very little data on the long-term outcome of patients with
      chronic hepatitis B after interferon therapy. A 6-year follow-up of two
      interferon trials in chronic hepatitis B patients is reported. METHODS: One
      hundred twenty-eight Chinese adults with chronic hepatitis B who received
      interferon therapy were followed for 19-79 months (median 41 months). Twenty-nine
      patients lost hepatitis B e antigen and two also lost hepatitis B surface antigen
      within 1 year of treatment. RESULTS: Seven (24%) responders reactivated. Twenty
      eight (28%) nonresponders had sustained clearance of hepatitis B e antigen during
      follow-up. Delayed clearance of hepatitis B e antigen occurred more frequently in
      nonresponders who had elevated pretreatment serum transaminase levels. (P =
      0.002). Serum hepatitis B virus DNA became undetectable by polymerase chain
      reaction assay in both responders who lost hepatitis B surface antigen but in
      only 8 (17%) patients who lost hepatitis B e antigen only. Delayed clearance of
      hepatitis B surface antigen was not seen in any of the 48 patients who had
      sustained clearance of hepatitis B e antigen. CONCLUSIONS: Contrary to reports
      from Western countries, complete elimination of markers of hepatitis B virus
      infection was uncommon in Chinese patients with chronic hepatitis B who underwent
      interferon therapy despite similar duration of follow-up.

PMID- 8253360
TI  - Early detection of protein depletion in alcoholic cirrhosis: role of body
      composition analysis.
AB  - BACKGROUND: Malnutrition is common in alcoholic cirrhosis. Bedside nutritional
      assessment techniques may be unreliable in patients with chronic liver disease.
      The aim of this study was to quantify changes in body composition and compare
      methods for measuring body composition in alcoholic cirrhosis. METHODS: Thirty
      eight men with alcoholic cirrhosis were compared with 16 age-matched healthy men.
      Body composition was assessed using anthropometry and bioelectrical impedance to
      determine fat-free mass and body fat, deuterium oxide dilution to measure total
      body water, in vivo neutron activation analysis to measure total body protein,
      and dual energy x-ray absorptiometry to measure bone mineral content and total
      body fat mass. RESULTS: With increasing severity of cirrhosis, total body water
      increased, whereas total body protein decreased with a significant decrease in
      serum albumin levels. Total body protein levels, expressed as an index, were a
      more sensitive indicator of protein depletion than serum albumin levels. When
      patients were assessed by anthropometry and bioelectrical impedance for fat-free
      mass, there was no reduction compared with controls. CONCLUSIONS: Anthropometry
      and bioelectrical impedance do not accurately reflect changes in body composition
      associated with chronic liver disease. Quantification of body composition changes
      in alcoholic cirrhosis requires the use of direct methods such as in vivo neutron
      activation analysis, dual energy x-ray absorptiometry, or deuterium oxide
      dilution.

PMID- 8253361
TI  - Enhanced expression of transforming growth factor beta isoforms in pancreatic
      cancer correlates with decreased survival.
AB  - BACKGROUND: Transforming growth factor beta s (TGF-beta s) constitute a family of
      bifunctional polypeptide growth factors that either inhibit or stimulate cell
      proliferation. Perturbations in TGF-beta expression and function may lead to loss
      of negative constraints on cell growth. In this study, we examined TGF-beta
      expression in human pancreatic cancer. METHODS: The distribution of TGF-beta
      isoforms in 60 human pancreatic cancers was examined using immunohistochemical,
      Northern blot, and in situ hybridization techniques. RESULTS: Immunohistochemical
      analysis showed the presence of TGF-beta 1 (47% of tumors), TGF-beta 2 (42% of
      tumors), and TGF-beta 3 (40% of tumors) in the cancer cells. The presence of TGF
      beta 2 was associated with advanced tumor stage (P < 0.05). Furthermore, there
      was a significant correlation between the absence of TGF-beta s in the tumors and
      longer postoperative survival. Northern blot analysis indicated that, by
      comparison with the normal pancreas, pancreatic adenocarcinomas showed 11- (P <
      0.001), 7- (P < 0.05), and 9-fold (P < 0.001) increases in the messenger RNA
      (mRNA) levels encoding TGF-beta 1, TGF-beta 2, and TGF-beta 3, respectively. By
      in situ hybridization, these mRNA moieties colocalized with their respective
      proteins in the cancer cells. CONCLUSIONS: These findings show that human
      pancreatic cancers show increased levels of TGF-beta isoforms and enhanced TGF
      beta mRNA expression and suggest that the presence of TGF-beta s in pancreatic
      cancer cells may contribute to disease progression.

PMID- 8253362
TI  - Updating prognosis in primary biliary cirrhosis using a time-dependent Cox
      regression model. PBC1 and PBC2 trial groups.
AB  - BACKGROUND: The precision of current prognostic models in primary biliary
      cirrhosis (PBC) is rather low, partly because they are based on data from just
      one time during the course of the disease. The aim of this study was to design a
      new, more precise prognostic model by incorporating follow-up data in the
      development of the model. METHODS: We have performed Cox regression analyses with
      time-dependent variables in 237 PBC patients followed up regularly for up to 11
      years. The validity of the obtained models was tested by comparing predicted and
      observed survival in 147 independent PBC patients followed for up to 6 years.
      RESULTS: In the obtained model the following time-dependent variables
      independently indicated a poor prognosis: high bilirubin, low albumin, ascites,
      gastrointestinal bleeding, and old age. When including histological variables,
      cirrhosis, central cholestasis, and low immunoglobulin (Ig)M also indicated a
      poor prognosis. The survival predicted by the models agreed well with the
      survival observed in the independent PBC patients. The time-dependent models
      predicted better than our previously published time-fixed model. CONCLUSIONS:
      Using the time-dependent Cox models, one can estimate a more precise probability
      of surviving the next 1, 3, or 6 months for any given patient at any time during
      the course of the disease. This may improve monitoring of PBC patients.

PMID- 8253363
TI  - Cholelithoptysis and cholelithorrhea: rare complications of laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy is now considered a safe procedure for the
      management of cholelithiasis. During the procedure, stone spillage can occur and
      is usually not considered a serious complication. Clearance of stones can be
      laborious and is often avoided. Two patients with complications from gross
      intraperitoneal stone spillage during laparoscopic cholecystectomy, namely
      cholelithoptysis and cholelithorrhea, are presented. Both patients developed
      cholelithoptysis, or the coughing up of gallstones, within 1 year of their
      laparoscopic surgery. In addition, the second patient also experienced the
      passage of stones from a fistula at the incision site of a remote lumbar
      laminectomy, which we term cholelithorrhea. We propose that cholelithoptysis
      developed from the transdiaphragmatic extension of intraperitoneal abscesses and
      the subsequent formation of bronchopleural fistulas. We believe that gross
      intraperitoneal stone spillage should be avoided and remedied, if possible, by
      removal of stones and copious irrigation.

PMID- 8253364
TI  - A man with type III glycogenosis associated with cirrhosis and portal
      hypertension.
AB  - Type III glycogenosis, an inherited disorder of glycogen metabolism that results
      from reduced or absent activity of the enzyme amylo-1,6-glycosidase (debranching
      enzyme), has not been frequently associated with cirrhosis and portal
      hypertension in adults. An adult Caucasian man with well-document type IIIa
      glycogenosis, who presented with a variceal hemorrhage secondary to hepatic
      cirrhosis, is described here. No other cause of cirrhosis was found.

PMID- 8253365
TI  - Erythromycin and other macrolides as prokinetic agents.

PMID- 8253366
TI  - An international traveler with fever, abdominal pain, eosinophilia, and a liver
      lesion.

PMID- 8253367
TI  - The unbearable lightness of being ... a cirrhotic.

PMID- 8253368
TI  - Endoscopic ligation versus sclerotherapy: is it time to jump on the bandwagon?

PMID- 8253369
TI  - New messenger for calcium entry.

PMID- 8253370
TI  - Acinar injury after biliopancreatic duct obstruction: is it necrosis?

PMID- 8253371
TI  - Lichen planus and interferon therapy for hepatitis C.

PMID- 8253372
TI  - Pathogenesis of nonsteroidal anti-inflammatory drug enteropathy.

PMID- 8253373
TI  - Gabexate mesilate in human acute pancreatitis.

PMID- 8253374
TI  - Precision in nutritional diagnoses.

PMID- 8253375
TI  - Long-term omeprazole therapy in peptic ulcer disease.

PMID- 8253376
TI  - Platelet-activating factor and nonalcoholic cirrhotics.

PMID- 8253377
TI  - Rescue of mice homozygous for lethal albino deletions: implications for an animal
      model for the human liver disease tyrosinemia type 1.
AB  - Mice homozygous for specific deletions around the albino locus on chromosome 7
      die within the first few hours of birth. They have a complex phenotype in liver
      and kidney, which includes multiple changes in gene expression and
      ultrastructural abnormalities. On the basis of this phenotype, it was proposed
      that these deletions remove a regulatory locus, alf or hsdr-1. Recently, we and
      others showed that the gene for fumarylacetoacetate hydrolase (Fah), an enzyme
      involved in tyrosine catabolism, was disrupted by the lethal albino deletion
      c14CoS. The finding that the Fah gene in wild-type mice is highly expressed only
      in cell types that develop a phenotype in mutants, and the fact that Fah
      deficiency determines the human liver disease hereditary tyrosinemia type 1
      (HT1), suggested that disruption of the Fah gene was responsible for the lethal
      albino phenotype. To test this hypothesis, we have created lines of mice carrying
      Fah transgenes. We find that c14CoS homozygotes which express transgenic Fah are
      complemented for all aspects of the complex lethal albino phenotype. Moreover,
      the degree to which the phenotype is corrected depends on the level of transgenic
      Fah expression. These results unequivocally establish Fah as the gene mapping at
      alf/hsdr-1 and prove that the phenotype depends ultimately on the blockage of
      tyrosine metabolism. Finally, they suggest lethal albino mice as an animal model
      for HT1.

PMID- 8253378
TI  - Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic
      dysfunction phenotype of lethal albino mice.
AB  - Mice homozygous for the c14CoS albino deletion die as neonates as a result of
      liver dysfunction. Previous mapping studies have associated this defect with a
      310-kb fragment encoding the hepatocyte-specific developmental regulation locus
      (alf/hsdr-1). The gene encoding fumarylacetoacetate hydrolase (Fah), a metabolic
      enzyme that catalyzes the last step of tyrosine catabolism, also maps to the same
      deletion interval. To test whether the neonatal defects found in the albino
      deletion mutants are attributable to loss of Fah, and not to another gene mapping
      to the deletion, we have generated Fah mutant mice by gene targeting in embryonic
      stem cells. Fah-deficient mice die within 12 hr after birth from hypoglycemia and
      liver dysfunction. In addition, the same pattern of altered liver mRNA expression
      found in the albino deletion mutants was also found in affected animals. We
      conclude that the neonatal lethal and liver dysfunction phenotype of the alf/hsdr
      1 deletion is entirely attributable to loss of Fah.

PMID- 8253379
TI  - Inhibition of mammary duct development but not alveolar outgrowth during
      pregnancy in transgenic mice expressing active TGF-beta 1.
AB  - The transforming growth factors beta (TGFs-beta) are potent inhibitors of cell
      proliferation and are usually secreted in a latent form. TGF-beta 1, TGF-beta 2,
      and TGF-beta 3 are expressed in distinct but overlapping patterns in the
      developing mouse mammary gland. To study the role of transforming growth factor
      beta 1 (TGF-beta 1) in normal mammary development and in mammary neoplasia, we
      have constructed three transgenic mouse lines that express a simian TGF-beta 1
      s223/225 mutated to produce a constitutively active product under the control of
      the MMTV enhancer/promoter. Expression of the transgene, as confirmed by in situ
      hybridization, immunohistochemistry, and Northern blot analysis, was associated
      with marked suppression of the normal pattern of mammary ductal tree development
      in female transgenics. Reduction in total ductal tree volume was observed at 7
      weeks, soon after estrous begins, and was most apparent at 13 weeks, as ductal
      growth in the normal mammary gland declines. This effect was seen in all three
      lines. However, during pregnancy, alveolar outgrowths developed from the
      hypoplastic ductal tree, and lactation occurred, therefore, all transgenic
      females could feed full litters. Unlike many other transgenic mouse models in
      which expression of growth factors or oncogenes under control of the MMTV
      promoter leads to mammary epithelial hyperplasia and increased tumor formation,
      the MMTV-TGF-beta 1S223/225 transgene causes conditional hypoplasia of the
      mammary ductal tree and no spontaneous tumors have been detected in the MMTV-TGF
      beta 1S223/225 transgenic animals.

PMID- 8253380
TI  - Locus-specific variation in phosphorylation state of RNA polymerase II in vivo:
      correlations with gene activity and transcript processing.
AB  - To investigate functional differences between RNA polymerases IIA and IIO (Pol
      IIA and Pol IIO), with hypo- and hyperphosphorylated carboxy-terminal repeat
      domains (CTDs), respectively, we have visualized the in vivo distributions of the
      differentially phosphorylated forms of Pol II on Drosophila polytene chromosomes.
      Using phosphorylation state-sensitive antibodies and immunofluorescence
      microscopy with digital imaging, we find Pol IIA and Pol IIO arrayed in markedly
      different, locus- and condition-specific patterns. Major ecdysone-induced puffs,
      for example, stain exclusively for Pol IIO, indicating that hyperphosphorylated
      Pol II is the transcriptionally active form of the enzyme on these genes. In
      striking contrast, induced heat shock puffs stain strongly for both Pol IIA and
      Pol IIO, suggesting that heat shock genes are transcribed by a mixture of hypo-
      and hyperphosphorylated forms of Pol II. At the insertion sites of a transposon
      carrying a hybrid hsp70-lacZ transgene, we observe only Pol IIA before heat shock
      induction, consistent with the idea that Pol II arrested on the hsp70 gene is
      form IIA. After a 90-sec heat shock, we detect heat shock factor (HSF) at the
      transposon insertion sites; and after a 5-min shock its spatial distribution on
      the induced transgene puffs is clearly resolved from that of Pol II. Finally,
      using antibodies to hnRNP proteins and splicing components, we have discerned an
      apparent overall correlation between the presence and processing of nascent
      transcripts and the presence of Pol IIO.

PMID- 8253381
TI  - New telomeres in yeast are initiated with a highly selected subset of TG1-3
      repeats.
AB  - The creation of new telomeres was studied by generating a site-specific double
      strand break in diploid strains of Saccharomyces cerevisiae that are unable to
      carry out homologous recombination. New telomere formation occurred approximately
      1% of the time but only when (T2G4)13 was present proximal to the break site.
      About half of the healing events occurred at a number of 1- to 9-bp G or G, T
      sequences located as far as 128 bp distal to the T2G4 repeats. Surprisingly, in
      16 events at sites ending in GTGG, the first TG1-3 nucleotides added always
      included either an 11- or a 13-bp sequence (GTGTGGGTGTG or GTGTGTGGGTGTG), after
      which each new telomere diverged into a less ordered TG1-3 pattern. Moreover, at
      75% of the remaining addition sites, these same 11- or 13-bp sequences were found
      overlapping the junction between the chromosomal primer and the newly added
      sequences. We propose that short G, T sequences near an organizing sequence such
      as (T2G4)13 can act as primers to pair with the template RNA of a telomerase and
      add new sequences that are complementary to that RNA.

PMID- 8253382
TI  - A distant 10-bp sequence specifies the boundaries of a programmed DNA deletion in
      Tetrahymena.
AB  - Programmed DNA deletion occurs at thousands of specific sites in most ciliates
      studied. To understand the mechanism of this prominent DNA rearranging process,
      we analyzed one of the deletion elements (the M-element) in Tetrahymena by making
      specific mutations in cloned DNAs and testing their effects on rearrangement in
      vivo. We found that a 10-bp polypurine sequence (5'-AAAAAGGGGG) plays a crucial
      role. This sequence is located at a short distance (approximately 45 bp) outside
      of the element on either side. Removal of it abolishes the deletion process.
      Moving it short distances away causes the deletion boundary to move with it.
      Insertion of this sequence into a site within the element induces new boundaries
      to form near the insertion site. Sequence analysis reveals that all new
      boundaries created are 41-54 bp away from the sequence. Thus, this sequence is
      necessary and sufficient to determine the boundaries of DNA deletion, and it does
      so from a short distance outside of the element. These results offer a possible
      explanation for the control of DNA deletion in ciliates and suggest that a new
      type of mechanism for site-specific DNA rearrangements is involved.

PMID- 8253383
TI  - The adenovirus E1A-associated 130-kD protein is encoded by a member of the
      retinoblastoma gene family and physically interacts with cyclins A and E.
AB  - The adenovirus E1A proteins form complexes with a group of cellular proteins,
      including a protein of 130 kD. E1A-associated p130 was purified through
      coimmunoprecipitation with E1A, and sequence data from four tryptic peptides was
      obtained. Oligonucleotides derived from the peptide sequences were used to clone
      a 4.85-kb cDNA. The cDNA contained an 1139-amino-acid open reading frame with
      homology to the retinoblastoma protein and E1A-associated p107 but was more
      closely related to p107. In vitro-translated p130 bound to E1A, and anti-p130
      antibodies detected p130 in immunoblots of E1A immunoprecipitates. p130 was also
      detected in immunoprecipitates of cyclins A and E and was an efficient substrate
      in vitro for kinase activities associated with these cyclins. The p130 gene
      mapped to chromosome 16q12.2-13, a region that undergoes allelic loss in several
      types of tumors, including hepatocellular, prostate, and breast carcinomas.

PMID- 8253384
TI  - Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins.
AB  - A two-hybrid protein interaction screen was used to isolate cDNAs encoding human
      proteins that can interact with human CDK2 in yeast. A new member of the
      retinoblastoma susceptibility gene family, Rbr-2 (Rb-related), was obtained. The
      sequence of the Rbr-2 protein shares approximately 50% identify with p107 and
      homology to Rb within the pocket domain. Several lines of evidence indicate that
      Rbr-2 is the adenovirus E1A-associated p130. Like Rb and p107, p130Rbr-2 can bind
      to viral oncoproteins, SV40 large T antigen, and adenovirus E1A through its
      pocket domain. Although p130Rbr-2 does not bind to CDK2 in vitro, it can interact
      with cyclins, with a clear preference for D-type cyclins. Because both CDK2 and
      p130Rbr-2 show affinity for cyclins, we suggest that p130Rbr-2 and CDK2
      interacted through a yeast-derived cyclin bridge in the two-hybrid screen. The
      gene encoding p130Rbr-2 mapped to 16q13, a region of frequent genomic alteration
      in human tumors.

PMID- 8253385
TI  - Cell cycle-specific association of E2F with the p130 E1A-binding protein.
AB  - Association of the E2F transcription factor with the pRb and p107 proteins
      appears to regulate the activity of E2F and, in turn, affect cell cycle
      progression. We found, however, that pRb and p107 are only minor E2F-associated
      proteins in G0/G1 mouse fibroblasts, and we sought to identify the major E2F
      partner protein in these cells. Because the adenovirus E1A oncoprotein seemed
      able to bind to the G0 E2F partner, we enriched for proteins that associated both
      with an E2F-binding site DNA column and with E1A. The major species in G0 and
      early G1 fibroblasts detected with this approach had properties identical to the
      pRb- and p107-related p130 protein. In serum-stimulated cells, p107 replaced p130
      as the major E2F-associated protein near the G1/S border, concomitant with an
      increase in p107 protein levels. p130-E2F complexes resembled p107-E2F complexes
      in their ability to bind to cyclin-cdk kinases, and they appeared to be
      associated with the cyclin E-cdk2 kinase in late G1 cells. These observations
      indicate that E2F transcription factors are regulated by a succession of partner
      proteins with which they associate during defined stages of the cell cycle.

PMID- 8253386
TI  - A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR
      proteins and stimulates U2 snRNP binding.
AB  - The inclusion of the 270-nucleotide human fibronectin ED1 exon in HeLa cells
      requires the presence of a centrally located 81-nucleotide exon sequence. We have
      conducted a series of in vitro experiments aimed at understanding the structural
      and functional features associated with this splicing enhancer (SE). Using hybrid
      model pre-mRNA substrates, we show that the SE element markedly stimulates the
      use of the 3' splice site of ED1. Deletion and replacement analysis identifies
      the stimulating sequences as a purine-rich stretch of 9 nucleotides (GAAGAAGAC).
      The SE element stimulates splicing to the ED1 3' splice site from various
      positions within the exon except when placed beyond 293 nucleotides downstream
      from that 3' splice site. The action of the enhancer is not limited to the ED1
      acceptor site because the SE element stimulates human beta-globin splicing and
      also induces the use of a 3' splice site in a prokaryotic sequence in vitro. We
      have explored the mechanism of action of the fibronectin splicing enhancer and
      found that the SE element is required for efficient assembly of early splicing
      complexes, allowing a more efficient interaction of the U2 snRNP with branch site
      sequences. In competition experiments, an RNA containing mainly SE sequences
      specifically abolished the action of the SE element, suggesting that factors bind
      the enhancer element to mediate stimulation of splicing. Using RNA mobility shift
      assays we show that SR proteins interact specifically with the SE element. Our
      results demonstrate that exon sequences lying in the SE element play a crucial
      role in specifying splice site recognition through interactions with factors
      binding to the 3' splice site.

PMID- 8253387
TI  - The hLEF/TCF-1 alpha HMG protein contains a context-dependent transcriptional
      activation domain that induces the TCR alpha enhancer in T cells.
AB  - hLEF/TCF-1 alpha is a lymphoid cell-specific HMG protein that activates the
      distal enhancer of the gene encoding the alpha-subunit of the T-cell receptor
      (TCR alpha). We have shown previously that transcriptional activation by hLEF is
      highly dependent on the context of its binding site within the TCR alpha
      enhancer. Here, we demonstrate that hLEF contains a potent transcriptional
      activation domain that is separate from the HMG motif and is preferentially
      active in T cells. We find that hLEF/GAL4 fusion proteins can activate a GAL4
      substituted TCR alpha enhancer up to 50-fold in T-cell lines and are as active as
      GAL4/VP16 in this context. Unlike GAL4/VP16, however, hLEF/GAL4 could not
      activate heterologous promoters bearing only GAL4 DNA-binding sites. Thus,
      activation by hLEF/GAL4, like that noted previously for the native hLEF
      activator, was strongly influenced by the context of its DNA-binding site within
      the TCR alpha enhancer. Inspection of enhancer mutants suggests that trans
      activation by hLEF/GAL4 is especially dependent on TCF-2, a distinct T-cell
      enriched protein that binds to sequences flanking the hLEF-binding site in the
      enhancer. Analysis of small deletion or clustered amino acid substitution mutants
      in the hLEF-coding sequences identified a minimal activation region between amino
      acids 80 and 256 that appears to be bipartite in structure. The hLEF activation
      domain is not notably acid or glutamine-rich but is proline-rich and includes a
      motif rich in tyrosine and serine residues. We conclude that sequences outside of
      the hLEF HMG box mediate cell- and context-specific activation of the TCR alpha
      enhancer and may facilitate interactions between hLEF and other T-cell-specific
      factors recruited to the enhancer.

PMID- 8253388
TI  - NRF-1, an activator involved in nuclear-mitochondrial interactions, utilizes a
      new DNA-binding domain conserved in a family of developmental regulators.
AB  - Nuclear respiratory factor 1 (NRF-1) was first discovered as an activator of the
      cytochrome c gene and was subsequently found to play a broader role in nuclear
      mitochondrial interactions. We have now cloned a HeLa cDNA encoding NRF-1 using
      degenerate oligomers derived from tryptic peptide sequences for PCR
      amplification. The cDNA-encoded protein was indistinguishable from the authentic
      HeLa cell factor on denaturing gels, displayed the expected NRF-1 DNA-binding
      specificity, and made the same guanine nucleotide contacts as HeLa NRF-1 on
      binding known NRF-1 recognition sites. Antiserum raised against the highly
      purified recombinant protein recognized the identical DNA-protein complex formed
      using either a crude nuclear fraction or nearly homogeneous HeLa NRF-1.
      Recombinant NRF-1 also activated transcription through specific sites from
      several NRF-1-responsive promoters, confirming both the transcriptional activity
      and specificity of the cDNA product. Portions of NRF-1 are closely related to sea
      urchin P3A2 and the erect wing (EWG) protein of Drosophila. Both are recently
      identified developmental regulatory factors. The region of highest sequence
      identity with P3A2 and EWG was in the amino-terminal half of the molecule, which
      was found by deletion mapping to contain the DNA-binding domain, whereas the
      carboxy-terminal half of NRF-1 was highly divergent from both proteins. The DNA
      binding domain in these molecules is unrelated to motifs found commonly in DNA
      binding proteins; thus, NRF-1, P3A2, and EWG represent the founding members of a
      new class of highly conserved sequence-specific regulatory factors.

PMID- 8253389
TI  - Amino-terminal amino acids modulate sigma-factor DNA-binding activity.
AB  - Prokaryotic transcription initiation factor sigma is required for sequence
      specific promoter recognition by RNA polymerase. Genetic studies have indicated
      that sigma itself interacts with DNA at the -10 and -35 promoter consensus
      sequences. Binding of Escherichia coli sigma 70 to DNA in vitro, however, can
      only be observed for truncated polypeptides lacking the amino-terminal amino
      acids. We have investigated the role of the amino terminus of E. coli sigma 70 in
      controlling DNA-binding ability. Deletion analysis indicates that amino acids
      within amino-terminal region 1.1 of sigma 70 inhibit DNA binding by the carboxy
      terminal DNA-binding domains. Furthermore, inhibition of binding by the amino
      terminal inhibitory domain of sigma 70 can be observed in trans. Likewise, the
      amino-terminal extensions of two alternative sigma-factors, E. coli sigma 32 and
      Bacillus subtilis sigma K, negatively affect the DNA binding activity of their
      carboxy-terminal domains. We propose that initiation of transcription is subject
      to modulation as a result of the composition and/or structure of the amino
      terminus of the sigma-subunit and that the sigma family of proteins belong to a
      larger class of intramolecularly regulated transcriptional effectors.

PMID- 8253390
TI  - Dimerization specificity of myogenic helix-loop-helix DNA-binding factors
      directed by nonconserved hydrophilic residues.
AB  - The myogenic regulatory factor MyoD dimerizes with other positive and negative
      regulatory factors through a conserved region called the helix-loop-helix (HLH)
      domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a
      dimerization competitor in gel mobility shift assays in conjunction with various
      MyoD HLH mutants, nonhydrophobic amino acids were identified in the HLH domain
      that contribute to dimerization specificity with E12. The assay detected subtle
      differences in dimerization activity among the mutant MyoD proteins that
      correlated with their ability to activate transcription in vivo, but this
      correlation was not apparent in the absence of competitor. The identification of
      such nonhydrophobic residues enabled us to predict the differences in
      dimerization affinity among the four vertebrate myogenic factors with E12. The
      experiments confirmed the prediction. Furthermore, a high-affinity homodimerizing
      analog of MyoD was designed by a single substitution at one of these residue
      positions. These experimental results were strengthened when they were analyzed
      in terms of the crystal structure for the Max bHLHZip domain homodimer. This
      analysis has allowed us to identify those residues that form charged residue
      pairs between the two HLH domains of MyoD and E12 and determine the dimerization
      specificity of the bHLH proteins.

PMID- 8253391
TI  - Translational positioning of a nucleosomal glucocorticoid response element
      modulates glucocorticoid receptor affinity.
AB  - Positioned nucleosomes are often found in enhancer/promoter regions where they
      confer defined positioning of trans-active-factor response element(s) relative to
      the histone octamer. Here, we address how this affects factor/response element
      recognition. We used 165-bp DNA segments containing one glucocorticoid response
      element (GRE) and rat liver core histones to reconstitute nucleosomes in vitro.
      The GREs in these nucleosomes were held in identical helical settings but
      different translational positions. This was achieved by placing the GRE within or
      at the flank of a 95-bp DNA-bending sequence. Glucocorticoid receptor (GR)
      binding experiments demonstrated that a GRE in free DNA has a 2.5-fold higher
      affinity for GR than the nucleosomal GRE when positioned 40 bp from the
      nucleosome dyad. A nucleosomal GRE positioned 40 bp from the nucleosome dyad, on
      the other hand, binds GR 4.3-fold better as compared to an identical GRE
      positioned 20 bp from the dyad and 1.4-fold better than a GRE positioned at the
      dyad. Interruption of the DNA-bending sequence, by a 5-bp AT segment next to a
      nucleosomal GRE positioned 20 bp from the dyad, restores GR affinity to the same
      level as when the GRE is placed 40 bp from the dyad. The effect on GR/GRE
      affinity either by different positioning within the 95-bp bending sequence or by
      introducing the 5-bp AT-segment is seen only in a nucleosomal context. We
      conclude that a translationally positioned nucleosome can modulate the affinity
      of a trans-active factor for its target response element.

PMID- 8253392
TI  - In search of the 'fountain of age'.

PMID- 8253393
TI  - Vascular dementia: how to make the diagnosis in office practice.
AB  - Vascular dementia is seen much more often in people at age 85 than in those
      between the ages of 55 and 75. The differential diagnosis includes Alzheimer's
      disease and mixed dementia. The classic criteria for vascular dementia--stepwise
      deterioration and focal neurologic signs--are important, as focal neurologic
      signs usually don't occur in Alzheimer's disease. Identifying a significant
      number of points on the Hachinski scale, including hypertension, can help make a
      diagnosis of vascular disease. For more effective differential diagnosis, CT or
      MRI can be useful. However, not all clinicians are convinced of the necessity of
      imaging, as long as stroke risk factors such as hypertension and hyperlipidemia
      are managed for all older patients.

PMID- 8253394
TI  - Use of serotonergic drugs for treating depression in older patients.
AB  - The selective serotonin reuptake inhibitors (SSRIs) offer a relatively new
      alternative to traditional tricyclic antidepressants (TCAs) in the treatment of
      depression in older adults. The two drug classes are equally effective, but SSRIs
      tend to cause fewer sedating, anticholinergic, or hypotensive effects and are
      unlikely to affect cardiac conduction. SSRIs also have a wider therapeutic window
      and are safer in cases of overdose. Potential side effects include GI distress,
      worsening of headaches, insomnia, and sexual dysfunction. Drawbacks of using
      SSRIs are their potential for drug interactions and relatively high cost.

PMID- 8253395
TI  - Betty Friedan: now she's making waves in the 'fountain of age'. Interview by
      Alice V Luddington.

PMID- 8253396
TI  - [Surgical treatment of tracheal obstruction in children].
AB  - 47 infants and children with tracheobronchial obstruction requiring surgical
      treatment are reported. 10 had subglottic stenosis; 17 severe tracheomalacia; 19
      intraluminal tracheal stenosis (in 2 of whom it was congenital); 12 granulation
      tissue or webs; 4 both tracheal stenosis and tracheal fistula; and 1 had a tear
      of the right main bronchus. The anterior cricoid splitting procedure for the
      management of severe acquired subglottic stenosis was performed in 10, in 2 of
      whom it failed and tracheostomy was required. Aortopexy was performed in 14 cases
      and pulmonary arteriopexy in 1. A rib cartilage graft and a prosthetic splint
      fabricated from Marlex mesh were applied in 2 cases after failed aortopexy. The
      19 patients with tracheal stenosis were treated as follows: tracheal splitting
      with autologous free tibial periosteal graft was used in 2 infants;
      transbronchoscopic resection was successful in 12 children; wedge resection of
      the tracheal fistula and anterior anastomosis was done in 4; segmental tracheal
      resection with end-to-end anastomosis in 1; and suture of a bronchial tear was
      performed in 1. There was no operative mortality; 2 patients died; but the deaths
      were not directly related to surgery. In our experience, the surgical approach is
      both safe and expedient in relieving tracheal obstruction in most infants and
      children.

PMID- 8253397
TI  - [Hodgkin's disease in childhood--northern Israel cancer center experience, 1971
      1990].
AB  - Records of children treated for Hodgkin's disease between 1971-1990 were analyzed
      retrospectively, and 102 cases of children younger than 18 years when diagnosed
      were reviewed. There were 54 boys and 48 girls, with male predominance in those
      younger than 10 years. 44 patients were of Arab ancestry and 58 were Jewish; the
      incidence was similar in both groups. Most common were the nodular sclerosing and
      mixed cellularity types, the latter more common in the younger age group. The
      outcome of various treatments was evaluated. At diagnosis, 64% were in stages I
      or II and 34% in stages III or IV. 20 of those in stages I-II received
      radiotherapy (RT) alone, 10 chemotherapy (CT) alone, and 35 combined CT and RT.
      Survival rates and median disease-free intervals were statistically similar with
      all 3 modalities. However, relapse rates were higher with either RT or CT alone
      (35% and 38%, respectively) than with combined therapy (14%). We conclude that
      combined CT and RT is superior to RT or CT alone.

PMID- 8253398
TI  - [Fine needle aspiration of thoracic lesions].
AB  - Recent radiologic techniques can detect masses as small as 1 cm in diameter. In
      combination with fine needle aspiration (FNA), quick and reliable diagnosis of
      thoracic lesions is now possible and the methods are now accepted worldwide.
      Several studies have shown that FNA is more sensitive than conventional cytology
      (including sputum smears and bronchoscopic brushes and washes). Although
      complications and risks are associated with FNA, they are minimal compared to
      those of thoracotomy. Between 1976-1990, FNA was performed on 107 patients with
      pulmonary lesions. In 97 of them, the aspirates were positive for malignancy in
      76%, in 7% there was a suspicion of malignancy, and 15% were negative. Diagnostic
      accuracy was similar for lesions 1 cm or 3 cm in diameter.

PMID- 8253399
TI  - [Serum striated muscle enzymes in autoimmune hypoparathyroidism].
AB  - Elevated serum levels of creatine phosphokinase (CPK) and lactate dehydrogenase
      (LDH) are generally present in cases of muscle or heart disease, though there are
      some exceptions. We treated a 56-year-old man diagnosed as suffering from primary
      idiopathic hypoparathyroidism (PIHP). The neurologic examination was normal, but
      serum levels of CPK and LDH, and especially isoenzymes of striated muscle, were
      elevated. Elevated levels of these enzymes in PIHP are rare. In this case they
      most probably leaked from muscle into the blood circulation after changes in the
      muscle cell membrane due to hypocalcemia.

PMID- 8253400
TI  - [Visits to emergency rooms and hospital ownership categories].
AB  - Trends in emergency room (ER) visits in Israeli general hospitals were analyzed
      and differences were found according to category of hospital ownership, Data for
      1986-90 were gathered from 23 hospitals which included 90% of the country's acute
      care beds. An upward trend in ER visits in the 1970's and early 1980's ended in
      1987. Despite a 7% increase in population during 1987-90, total ER visits
      decreased by 4%. In Jerusalem's public hospitals ER visits decreased by 13%, in
      government and government-municipal hospitals by 7%, while in Kupat Holim Clalit
      hospitals there was a 2% increase. The proportion of ER visits resulting in
      hospital admissions also varied by hospital ownership and also among individual
      hospitals within any given ownership category. Factors which might influence ER
      visits include size and composition of populations, development of alternative
      sources of care in the communities, price of services, changes in hospital
      admission policies, nature of the competition between hospitals, supply of
      physicians, and the use of ER's for primary care.

PMID- 8253401
TI  - [Acanthamoebic keratitis].
AB  - Acanthamoebic keratitis is still a rare infection. It occurs in contact lens
      wearers, especially when saline is prepared at home from contaminated tap water.
      There are periods of remission, and occasionally misleading findings resembling
      those of herpetic keratitis, which make the diagnosis difficult. The isolation of
      the acanthamoeba is not easy and special culture media are required. Early
      recognition and aggressive therapy with antiamebic medication and epithelial
      debridement, often in conjunction with penetrating keratoplasty, are needed. We
      describe the clinical course, laboratory diagnosis and treatment of 3 patients
      with acanthamoebic keratitis, 2 men aged 20 and 25, respectively and a women aged
      42.

PMID- 8253402
TI  - [Intestinal cystic duplication in infants and the etiology of intussusception].
AB  - 2 infants, 3 months old and 8 months, respectively, with restlessness and
      vomiting were each found to have ileocolic intussusception with barium filling
      defects. Laparotomy disclosed in each a dome-shaped structure, 2 cm and 0.6 cm in
      greatest diameter, respectively, on the antimesenteric side of the ileal wall.
      Histological examination showed cystic duplication of the ileum. It is suggested
      that manual reduction generally fails when cystic duplication is an etiological
      factor, and surgery is then mandatory.

PMID- 8253403
TI  - [Relationship between metals in the body and psychiatric disorders].

PMID- 8253404
TI  - [Use of silicone implants for breast augmentation].

PMID- 8253405
TI  - [Silicone implants for breast augmentation and autoimmune disease].

PMID- 8253406
TI  - [Gastrointestinal manifestations in AIDS].

PMID- 8253407
TI  - [Extracorporeal photopheresis--a new therapeutic concept].

PMID- 8253408
TI  - [Role of surgery in small cell lung cancer].

PMID- 8253409
TI  - [Disturbances in eustachian tube function--role of experimental studies].

PMID- 8253410
TI  - [AIDS and the physician].

PMID- 8253411
TI  - [Laser circumcision--Halachi problems].

PMID- 8253412
TI  - [Silicone gel implants--a medical hazard or false alarm?].

PMID- 8253413
TI  - [Tuberculosis in the community: viewpoint of the family physician].
AB  - In 1991, 3 patients of an overall patient population of 1400 were found to be
      suffering from active tuberculosis (TB). They were long-time residents of Israel
      and were not of Ethiopian origin. 2 had TB of the lymph-nodes of the head and
      neck and the third had pleural TB with involvement of the ribs. In each case TB
      was diagnosed retroactively; the original presumptive diagnosis was malignancy.
      This relative increased incidence of TB should increase our awareness of this
      disease.

PMID- 8253414
TI  - [Primary tuberculosis of the glans penis].
AB  - Primary tuberculosis of the glans penis is extremely rare. We report a case in a
      70-year-old man who presented with a deep ulceration of the ventral surface of
      the glans which mimicked malignancy. The diagnosis of tuberculosis was confirmed
      by biopsy, culture, and response to antituberculous chemotherapy. There was no
      coexisting tuberculous infection elsewhere.

PMID- 8253415
TI  - [Serological screening for Lyme disease in Israel].
AB  - During 1989-1992, 123 serum samples from patients with dermatological or
      neurological disorders were tested for Lyme disease antibody. In only 1 case was
      a diagnosis of autochthonous Lyme disease confirmed. 8.9% of the samples were
      positive for antibody to the 41kD flagellar antigen of Borrelia burgdorferi
      (ELISA test) and 7.3% for the 39kD protein (immunodot test). The diagnosis of
      Lyme disease should be confirmed by carefully timed tests to detect antibody
      against multiple species-specific bacterial antigens.

PMID- 8253416
TI  - [Experience with biofragmentable anastomotic rings].
AB  - During 1991-92 we performed 50 bowel anastomoses using the biofragmentable
      anastomotic ring (BAR). The indications were malignancy (35 cases), Crohn's
      disease (3), dolichosigma (4), diverticulitis (2), gastric outlet obstruction
      (2), and 1 each for abdominal trauma, postoperative stricture, and stricture
      caused by ischemic colitis. The average age was 61; 28 were women and 22 men. The
      anastomoses were between colon and rectum (21 cases), ileum and colon (18), colon
      and colon (8), stomach and jejunum (2) and ileum and ileum (1). First stools were
      passed after an average of 4.7 +/- 2.5 (SD) days and a low-residue diet was well
      tolerated after an average of 7 +/- 3.9 days. There were complications in 12
      (24%). In 3 others leaks necessitated reoperation. Incomplete small bowel
      obstruction developed in 6, 4-18 days after operation and lasted 3-11 days. In 2
      a perianastomotic inflammation appeared 1-3 weeks after operation and was treated
      successfully with IV antibiotics and bowel rest. In 1 case a stricture appeared 3
      months after surgery and was treated successfully with balloon dilatation. No
      complications were seen after anastomosing bowel segments proximal to the
      ileocecal valve. The average time for expelling the BAR in 19 of the 45 patients
      was 2.5 +/- 0.6 weeks, assessed by weekly X-raying of the abdomen. Although the
      group of patients was small, our impression is that the method of anastomosis is
      easy to learn, easy to perform and relatively safe.

PMID- 8253417
TI  - [Cobra bite: ophthalmic manifestations].
AB  - The venom of the cobra snake contains a mixture of several toxic enzymes and
      proteins. It has a direct action on the respiratory centers, as well as
      curariform interference at the neuromuscular junction, resulting in death from
      respiratory paralysis. It can injure the visual system by damaging the retinal
      cells, causing bilateral optic neuritis and cortical blindness. Due to a
      particular configuration of its venom ducts, the African cobra is capable of
      poisoning both by biting or by spitting its venom. We present an 18-year-old
      woman with severely impaired visual function which resulted from a cobra bite in
      childhood.

PMID- 8253418
TI  - [Adverse effects of tamoxifen on the female genital tract].
AB  - Tamoxifen is an established adjuvant therapy for breast cancer. It exerts both
      estrogenic agonist and antagonist effects on target tissues. Since the use of
      tamoxifen is expanding, it is expected that more women will suffer from its side
      effects. 3 women aged 48, 48, and 65, respectively, who were treated with
      tamoxifen, were referred for evaluation of possible side-effects. They had,
      respectively, endometrial hyperplasia, a unique sonographic appearance of the
      endometrium resembling neoplasia, and an ovarian cyst.

PMID- 8253419
TI  - [Gemfibrozil-induced myopathy].
AB  - A 61-year-old woman with hyperlipidemia was treated with gemfibrozil. She also
      had insulin-treated diabetes mellitus and chronic renal failure and was admitted
      because of severe chest pain. The ST segment was depressed and creatine kinase
      levels were elevated. The original diagnosis was acute myocardial infarction. In
      the presence of increasing chest pain, the onset of limb muscle tenderness, and
      increasing levels of creatine kinase, the diagnosis of myopathy secondary to
      gemfibrozil therapy was made and the drug was discontinued. All symptoms then
      subsided and creatine kinase levels returned to normal. Myopathy is a well-known
      complication of blood lipid-lowering drugs, especially in patients with renal
      failure.

PMID- 8253420
TI  - [Dideoxynucleoside therapy in acquired immunodeficiency syndrome].

PMID- 8253421
TI  - [Pregnancy and the human immunodeficiency virus].

PMID- 8253422
TI  - [Reimbursement for mental health treatment--past, present and future].

PMID- 8253423
TI  - [Postpartum blues and depression].

PMID- 8253424
TI  - [Considerations behind changing current management policy for minor head injury].

PMID- 8253425
TI  - [Eosinophilia-myalgia syndrome].

PMID- 8253426
TI  - [Role of the hospital director: an interorganizational comparison].
AB  - This study analyzes the role of the medical director of general hospitals in
      Israel. 26 directors of general hospitals were interviewed, of whom 7 managed
      independent or nonprofit hospitals, and 19 government or Kupat Holim Clalit
      hospitals. In Israel, hospital directors deal mainly with issues referred to in
      the literature as the "production" of hospital outputs and spend less time
      adapting the hospital to its changing environment. Accordingly, hospital
      directors spend only one-fifth of their time outside the hospital negotiating
      with outside agencies, and half of their time in their offices. More than 2/3 of
      the directors expressed dissatisfaction with the way they allocated their time,
      and said they would prefer to spend more time on long-term planning, quality
      control, and professional development, and less on ongoing operation. The
      management style of directors of independent hospitals was less centralized and
      they perceived themselves as having more authority than did directors of
      hospitals which are part of large, public, multihospital organizations. The
      independence of hospitals and the creation of a more competitive hospital market
      may make adapting the hospital to its changing environment a central part of the
      hospital director's agenda. Moreover, as hospitals gain more independence,
      directors will be granted broader authority and will have to assume more
      responsibility. These changes will require directors to adopt a different
      managerial orientation than that indicated by the findings of this study.

PMID- 8253427
TI  - [Abuse of the elderly: extent, diagnosis, treatment].

PMID- 8253428
TI  - [A visitor's view of the prospects for primary care and medical education in
      Israel].

PMID- 8253429
TI  - [Janusz Korczak--a clinician without a clinic].

PMID- 8253430
TI  - [Damage control--a new operative approach to trauma].

PMID- 8253431
TI  - [Ion-selective microelectrodes for intracellular measurements].
AB  - Ion-selective electrodes have been used for many years to analyze ion activities
      in electrolyte solutions. In recent years, these electrodes have been
      miniaturized and applied for measurements in the cell interior. This article
      describes basic principles for both the fabrication and the intracellular
      application of ion-selective microelectrodes, particularly focusing on double
      barreled liquid ion-exchanger microelectrodes. The use of ion-selective
      microelectrodes allows continuous and real-time measurements of intracellular ion
      activities of a single cell in both multicellular and isolated cell preparations
      under various conditions, such as changes in ion composition of the extracellular
      bathing fluid and exposure to certain drugs. With double-barreled ion-selective
      microelectrodes, the transmembrane potential and intracellular ion activities can
      be measured simultaneously in the same cell. Although there are still some
      problems or limitations to the intracellular application of ion-selective
      electrodes, this technique is useful for determining the actual movement of
      intracellular ions, and thereby to elucidate cellular mechanisms of membrane
      transport and other physiological functions.

PMID- 8253432
TI  - [Application of a Fotonic Sensor for measurement of chronotropy and contractility
      in cultured rat cardiac myocytes].
AB  - We used a Fotonic Sensor, a fiber optic displacement measurement instrument, to
      measure the chronotropy and the contractility of cultured neonatal rat cardiac
      myocytes. The principle of the measurement is to detect changes in the distance
      between the probe and myocytes vertically extruded by the contraction. A fiber
      optic probe consists of adjacent pairs of light-transmitting and light-receiving
      fibers. The ratio of reflected light to transmitted light changes proportionally
      to the distance between the probe and an object at a certain range shown in a
      calibration curve. The analogue output from the sensor was transferred to a
      personal computer through an analogue/digital converter and analyzed. The sensor
      was able to detect the rate of myocyte beating, i.e., chronotropy, with a high
      correlation to the frequency of electrically stimulated beating and agreed well
      with the beating rate counted visually under a microscope. The contractility was
      evaluated by the maximum contraction velocity (Vm) by the first derivatives of
      the contraction curves obtained by the sensor. Norepinephrine (NE) and
      isoproterenol (ISO) increased the contractility in cultured myocytes in a dose
      dependent fashion. In the preparation of rat ventricular papillary muscle, NE-
      and ISO-induced increase in the Vm in the radial direction significantly
      correlated with the increase in tension measured with a force-displacement
      transducer. These results indicate that the Fotonic Sensor is an appropriate
      instrument for evaluating the chronotropy and the contractility of cultured
      myocytes.

PMID- 8253433
TI  - [A method employing housing in a radial maze apparatus for estimating working
      memory in mice: effects of scopolamine and delay upon maze performance].
AB  - Male ddY mice were housed in a 4-, 6-, or 8-arm radial maze apparatus for 6 hr a
      day and then removed to a normal cage for fasting until the next day's trial. A
      water bottle was placed at the central platform. The end of each arm ran to the
      home cage through a guillotine door (G). Food was placed in the home cage. During
      the housing in the apparatus, one G was opened, and the remaining Gs were shut.
      The opened G was changed in random order during the housing period of 6 hr. At
      the beginning of the trial, all Gs were shut. The mouse was placed on the
      platform and was permitted to choose the arms until it chose all arms. When the
      mouse chose the last arm, the G was opened to allow stepping into the home cage.
      The mice housed in these apparatus learned to go to the home cage without
      entering already chosen arms within 4-6 days. Scopolamine (0.2 and 0.4 mg/kg,
      i.p.) impaired the maze performance. A 1- to 4-min delay impaired the performance
      slightly, but did not show any significant effect depending on the delay
      intervals. These results suggest that the apparatus is a useful and easy method
      for estimating working memory and the drug effects thereon in mice.

PMID- 8253434
TI  - Diastasis of bipartite sesamoids of the first metatarsophalangeal joint.
AB  - Injury to the metatarsophalangeal (MP) joint of the great toe, often termed "turf
      toe", is a common occurrence in football. We have identified four cases of first
      MP plantar capsular injury with diastasis of a bipartite sesamoid. In three
      cases, observation and protection resulted in progressive widening of the
      fragments associated with pain and disability. These players required resection
      of the distal sesamoid fragment and repair of the volar capsule. The fourth
      player underwent acute repair of the medial retinaculum and capsule. All players
      have had a full return to sports activity. Diastasis of components of a partite
      sesamoid provides objective evidence of disruption of the plantar capsular
      mechanism. Early recognition of this condition confirmed by stress radiographs is
      recommended. Treatment may include early protection followed by resection, if
      painful, or acute repair of the retinaculum. Previous descriptions of turf-toe
      have not included injuries to the sesamoid complex of the first MP joint. In our
      opinion, the term turf-toe should represent the consequences of a hyperextension
      injury to the first MP joint in which the volar capsule has been disrupted
      proximal to the sesamoid. A classification for first MP joint injuries is
      presented.

PMID- 8253435
TI  - The blood supply to the great toe sesamoids.
AB  - The purpose of this study was to define the intraosseous and extraosseous blood
      supply of the hallucal sesamoids by studying a total of 10 fresh-frozen, below
      knee specimens with no evidence of vascular disease. Most specimens were injected
      with high grade India ink, cleared using a standard Spalteholz technique, and
      processed to delineate the extraosseous and intraosseous blood supply to include
      soft tissue dissection and coronal sectioning. Two additional specimens were
      injected with blue Mercox acrylic solution to further define the extraosseous
      vasculature. The major extraosseous blood supply to the sesamoids is via the
      posterior tibial artery. This vessel then branches into the medial plantar artery
      which further divides upon entering the medial and lateral sesamoids in their
      proximal poles. Vessels in the peripheral soft tissues, although abundant, do not
      seem to penetrate the cortex of the sesamoids. The intraosseous blood supply to
      the sesamoids seems to be threefold. Mainly, sesamoid arteries enter the lateral
      and medial sesamoids from the proximal aspect via a single vessel. This proximal
      vessel proceeds distally with a network of branching. Plantar, nonarticular
      vessels enter the sesamoids, constituting a second source of vascularity.
      Finally, small vessels also enter the sesamoids through medial and lateral
      capsular attachments. Based on this study, a possible explanation for avascular
      necrosis and nonunion of sesamoids is proposed, and an optimal surgical approach
      is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253436
TI  - Repair of chronic Achilles tendon rupture with flexor hallucis longus tendon
      transfer.
AB  - A new technique is described for reconstruction of chronic Achilles tendon
      rupture using the flexor hallucis longus tendon. Follow-up on seven patients
      (mean age 52 years) is provided (average follow-up 17 months, range 3-30 months).
      All patients were re-examined to assess postoperative range of motion, scar
      healing, and sensation. Motor strength was assessed by Cybex testing. Subjective
      satisfaction was examined by completion of a questionnaire. There were no
      postoperative infections, skin losses, or re-ruptures. Each patient developed a
      small but functionally insignificant loss in range of motion in the involved
      ankle and great toe. All patients had a satisfactory return of function. One
      patient required a molded foot-ankle orthosis for extended ambulation but was
      able to play golf.

PMID- 8253437
TI  - The treatment of rigid metatarsus adductovarus with the use of a new hinged
      adjustable shoe orthosis.
AB  - A retrospective review of the early results of treatment of metatarsus
      adductovarus with a new hinged adjustable shoe orthosis, the Bebax shoe, is
      presented. The results in 120 cases (210 feet) are included in the study.
      Criteria for severity of the initial deformity were developed, and all cases of
      true clubfoot and those cases with prior treatment were excluded. The average age
      at institution of treatment was 4.5 months, and treatment time averaged 2.7
      months (range 1-7 months). Overall, 96% of the cases were completely resolved
      with the use of the orthotic alone, 3% required additional casting, and 1%
      required a bar and shoes for complete correction of the deformity. No treatment
      complications were encountered except some minor problems with hinge loosening,
      particularly in the child of walking age. We believe that the Bebax shoe is a
      lightweight, convenient, safe, and both cost- and treatment-effective device in
      the management of metatarsus adductovarus.

PMID- 8253438
TI  - An anatomic and radiographic investigation of the tibiofibular clear space.
AB  - The tibiofibular clear space, a commonly used parameter in assessing the
      reduction of the syndesmosis in the management of ankle injuries, its anatomic
      boundaries, and resultant diagnostic ramifications were evaluated. This interval
      is seen to reflect the posterior aspect of the distal tibiofibular relationship
      and to vary not only with direct lateral displacement of the distal fibula but
      also potentially with rotational abnormalities of the fibula.

PMID- 8253439
TI  - Stress diagnostics of the sprained ankle: evaluation of the anterior drawer test
      with and without anesthesia.
AB  - This study investigated the effect of anesthesia of the peroneal communis nerve
      on stress diagnostics in acute ankle ligament rupture. Using a special holding
      device, the anterior drawer sign was measured under loading of 4 to 15 kg with
      and without a peroneal nerve block. In 65 patients, we found a highly significant
      difference between these two conditions. In a total of 110 patients, the
      measurement of anterior drawer sign was correlated to other diagnostic
      procedures. Absolute values of mechanical anterior drawer sign had a correlation
      of 0.479, whereas the difference of the measurements in injured and noninjured
      feet correlated with 0.582. We suggest anesthesia in stress diagnostics to
      increase accuracy. The anterior drawer sign alone, even under anesthesia, is not
      reliable to detect the full extent of the ligament damage.

PMID- 8253440
TI  - Ultrasound diagnosis of plantar fasciitis.
AB  - There is currently no objective reliable diagnostic test for plantar fasciitis
      inasmuch as diagnosis cannot be made on the basis of finding a heel spur on
      radiography (x-ray). In this single-blind observational study, ultrasonography
      was used to measure plantar fascia thickness in subjects with clinically
      suspected plantar fasciitis and in control subjects. It was concluded that the
      population mean plantar fascia thickness is greater for people with plantar
      fasciitis than for people without heel pain (P < .0005) and that the difference
      is clinically significant. The ultrasonic appearance of the plantar fascia in
      plantar fasciitis indicated inflammatory changes.

PMID- 8253441
TI  - Pigmented villonodular synovitis of the subtalar joint: a case report.

PMID- 8253442
TI  - Foot and ankle manifestations of Charcot-Marie-Tooth disease.
AB  - The term Charcot-Marie-Tooth disease represents a spectrum of neurological
      dysfunction more recently described as hereditary motor-sensory neuropathies. An
      abnormality of myelination is thought to be responsible for the clinical
      manifestations. While histological findings have been well described, the exact
      biochemical basis for this disorder remains unknown. Over one half of patients
      with Charcot-Marie-Tooth disease manifest foot and ankle problems, including
      pain, weakness, deformity, and, rarely, paresthesias. Characteristic patterns of
      neuromuscular weakness have been identified. Bilateral pes cavovarus is the most
      common pathologic foot deformity seen. The specific components include hindfoot
      varus, anterior or forefoot cavus, and, often clawtoes. The etiology of this
      abnormal foot posture usually results from tibialis posterior overpowering
      peroneus brevis coupled with peroneus longus overpowering tibialis anterior.
      Multiple treatment options have been described. Rationale for specific tendon
      transfers, soft tissue release, osteotomies, and arthrodesis is discussed.
      Results of surgical intervention are difficult to interpret and compare because
      of the wide spectrum of both neurological dysfunction and described operative
      procedures. In the presence of flexible deformity, early soft tissue release and
      tendon transfers may help prevent or delay more extensive bony procedures. The
      clinical results of triple arthrodesis in the Charcot-Marie-Tooth disease patient
      appear to deteriorate with time. Genetic transmission, progression of the
      neurological dysfunction, flexibility of the deformity, distribution of muscular
      weakness, and anticipated foot demands vary a great deal within this patient
      population. Treatment decisions, therefore, must be individualized and based upon
      a clear history, careful examination, and well-defined patient goals.

PMID- 8253443
TI  - [Unilateral paralysis of the vocal fold: correlation between laryngoscopy and
      electromyography].
AB  - From a clinical point of view, unilateral vocal fold paresis means that one of
      the vocal folds shows reduced mobility. Etiology may be mechanical or
      supranuclear, but in most cases it is a partial peripheral neurogenic lesion in
      the muscles innervated by one of the recurrent laryngeal nerves. On the one hand,
      a retrospective analysis was made of 71 cases with laryngoscopically reduced
      mobility of one vocal fold: 58 patients had electromyographic signs of partial
      denervation; 13 had normal electromyographic activity. Possible explanations are
      mechanical factors, paradoxical reinnervation, or central neurological pathology.
      On the other hand we reviewed 179 cases with an electromyographic diagnosis of
      unilateral partial peripheral neurogenic lesion in the muscles innervated by one
      of the recurrent laryngeal nerves: 119 patients showed a clinically immobile
      vocal fold, 2 a normally moving vocal fold and 58 a paretic vocal fold. A lot of
      immobile vocal folds are thus partial denervations. Insufficient amount of
      functional motor units and paradoxical reinnervation provide possible
      explanations.

PMID- 8253444
TI  - Accuracy of articulatory movements of speech in a group of first-graders.
AB  - Associations between different types of misarticulations and morphology as well
      as function of the speech articulators were assessed in 287 first-grade children.
      Sounds produced too far anteriorly evidently were due to immaturity of the
      articulatory speech movements, which showed a tendency to improve spontaneously
      with age. Sounds produced too far posteriorly correlated positively with problems
      in coordinating the movements of different muscles of the tongue, indicating a
      possible dyspractic origin. Children who had problems with lip tonus were prone
      to have laterally produced misarticulations.

PMID- 8253445
TI  - The effect of sustained phonation at high and low pitch on vocal jitter and
      shimmer.
AB  - Looking for possible signs of vocal fatigue, acoustic waveform perturbation was
      measured in normal female subjects during sustained phonation at various
      fundamental frequencies (Fo). At none of the pitch levels a rise of the jitter or
      the shimmer was found after 25 min of vocalization. On the other hand, an effect
      of Fo was seen from the start: above the habitual speaking Fo of our subjects'
      voices there was a tendency for the jitter to be higher and for the shimmer to be
      lower.

PMID- 8253446
TI  - [Spectral analysis of sounds produced by musical instruments and other sounding
      bodies for hearing screening of children].
AB  - Some time ago audiological screening in infants was mostly performed using
      musical instruments or equivalents. The use of acoustic evoked potentials and oto
      acoustic emissions changed the strategies of hearing assessment in newborns and
      infants, however, musical instruments are still in use. An adequate
      interpretation of screening results obtained with musical instruments
      necessitates a profound knowledge of frequencies and intensities derived from
      these instruments. In this study spectral analyses of sounds from these
      instruments were performed. The results may be of value for those using musical
      instruments as a tool for audiological screening. In addition, the results show
      that with some instruments intensities able to cause inner ear damage can be
      generated.

PMID- 8253447
TI  - Velocardiofacial syndrome: analysis of phoniatric and other clinical findings.
AB  - We present 18 children with velocardiofacial syndrome. A palatal or a submucous
      cleft was observed in 10 patients, while 8 had no cleft. Seven patients had minor
      anomalies in the CT scan, but their significance is unclear. These anomalies as
      well as structural cardiac malformations occurred more often in the non-cleft
      patients. Cleft palate and velopharyngeal insufficiency were not the only causes
      of speech problems in these children. In the velocardiofacial syndrome speech
      disorder should be recognized and carefully analyzed with phoniatric and
      neuropsychological methods.

PMID- 8253448
TI  - [Physiology and acoustic analysis of whistle voice of the woman].
AB  - Only a few singers are able to use to whistle voice, normally to produce
      extremely high pitches at the upper limit of their range. The laryngeal mechanism
      of the whistle voice is not completely understood. Stroboscopy shows only a
      horizontal vibration, the entire length of the vocal cords vibrating. The vocal
      cords are stretched to their maximal length. The spectral analysis of the whistle
      voice shows that the first two partials are much more pronounced than the higher
      ones. The 3D-PAN of the modal register is more complex than that of the whistle
      register.

PMID- 8253449
TI  - [Reliability of assessment of audible stuttering behavior].
AB  - The authors examine the essential aspects of the behaviour of the stutterer as
      perceived by the ear and discuss the reliability of the appreciation. The method
      of molecular analysis of speech samples of children aged from 7 to 12 years is
      described. The conclusion is that using this method, four out of the six
      categories of children examined show complete concordance and can be repeated as
      required; this is particularly true insofar as elongations, blockages,
      repetitions and interjections are concerned. However, one cannot consider as
      valid criteria the length of the pauses and the quality of breathing during
      phonation.

PMID- 8253450
TI  - Additional information about the central auditory discrimination ability of
      aphasics.
AB  - The differences of sensorimotor (global) and motor aphasias using
      electrophysiological recordings of cortical regions after different acoustic
      stimuli are described. For appreciation of the auditory perception ability of
      patients with aphasia slow auditory evoked potentials were recorded from temporal
      regions, after stimulation with tone, white noise, and word stimuli. For the
      global aphasia group (with speech comprehension lesion) normal cortical complexes
      were not recorded. These results could contribute to the discrimination of the
      two main types of aphasia (global and motor).

PMID- 8253451
TI  - [Experimental study of respiration in spontaneous dialogue].
AB  - The breathing patterns of two speakers engaging in a spontaneous conversation
      were studied. The variations observed in duration and air flow on inspiratory and
      expiratory phases indicated the following: Two of the factors which determine
      respiratory rhythm during speech are inspired air volume and expiration duration.
      The pragmatic constraints of dialogue constitute genuine constraints, such that
      the speaker's breathing is adapted to the dialogue rather than the dialogue being
      adapted to the breathing. No respiratory evidence was found to support the
      hypothesis of verbal unit ("sentence") preprogramming. On the contrary, the close
      relationship between conversational phenomena and respiratory phenomena indicates
      that there are no complete verbal units in dialogue.

PMID- 8253452
TI  - High-resolution frequency analysis as applied to the singing voice.
AB  - We have applied high-resolution vocal frequent analysis to a population of
      singing voices. Two important elements have become apparent: (1) Confirmation
      that the singing formant originates in the resonators. This is observed
      especially on a low fundamental, and it is acquired through technical skill and
      experience. (2) Observation of the vibrato, which, isolated from the clinical
      study, regarding only its graphic presentation, could have been interpreted as
      'abnormal'.

PMID- 8253453
TI  - Evoked otoacoustic emissions in children in relation to middle ear impedance.
AB  - The influence of changes in middle ear impedance with and without serotympanon on
      the measurement of evoked otoacoustic emissions (EOAE) was investigated in 108
      children between 3 and 12 years of age. Children with proven serotympanon never
      showed good EOAE. In those who only had changes in middle ear impedance without a
      serotympanon, the decrease in EOAE amplitude was more related to the magnitude of
      conductive hearing loss than to the change in impedance itself. These results are
      compared with those of a neonatal screening project in which some of the 532
      healthy fullterm newborns showed poor emissions in the first days of life. It
      seems reasonable to assume that this is due to incomplete pneumatization of the
      middle ears of these children, especially as a control audiogram later in their
      lives showed normal hearing thresholds.

PMID- 8253454
TI  - [Auditory lateralization in monozygotic twins: a study with dichotic consonant
      vowel recall].
AB  - Auditory lateralization was examined in 21 monozygotic twin pairs (n = 42) and 52
      singletons (healthy volunteers). Nine of the twin pairs were discordant for
      handedness, and 12 consisted of concordantly right-handed persons. All subjects
      were studied with a German dichotic consonant-vowel recall test using the
      syllables /ka/, /ta/, /pa/, /ga/, /da/ and /ba/ as stimuli. There was (i) a
      marked right-ear advantage in right handed singletons (as expected), (ii) no
      significant ear advantage among monozygotic twins (neither among those concordant
      nor those discordant handedness), and (iii) no relation between the direction of
      ear advantage within twin pairs. These data suggest that auditory lateralization
      is largely determined nongenetically.

PMID- 8253455
TI  - Are patients with neoplasia at an increased risk for cardiac myxomas?
AB  - A case-control study was undertaken to assess whether a significant association
      exists between the presence of a neoplasm or malignancy and the presence of a
      cardiac myxoma. We identified 13 patients seen at our institution between 1935
      and 1990 whose autopsies revealed a cardiac myxoma that was undetected during the
      patient's lifetime. For each patient four control subjects were selected among
      the autopsied patients who had never had a cardiac myxoma; these were matched for
      age at death, gender, and year of autopsy. The institutional medical records and
      autopsy reports revealed that 46% of the patients and 65% of their controls had a
      neoplasm diagnosed prior to or at autopsy. The estimated odds ratio was 0.34 (95%
      confidence interval, 0.05 to 1.84). There was insufficient evidence to conclude
      that an association exists between the presence of a neoplasm and the presence of
      a cardiac myxoma (P = .2722).

PMID- 8253456
TI  - Detection of human papillomavirus DNA by in situ hybridization and polymerase
      chain reaction in human papillomavirus equivocal and dysplastic cervical
      biopsies.
AB  - One hundred twenty-one paraffin-embedded cervical biopsy specimens were tested
      for the presence of human papillomavirus (HPV) DNA by in situ hybridization and
      polymerase chain reaction. By in situ hybridization using probes for HPV types
      6/11, 16/18, 31/33/35, 42/43/44, 51/52, and 45/56, HPV DNA was found in none of
      20 normal/squamous metaplasia biopsy specimens, in one of 76 HPV equivocal biopsy
      specimens, in seven of 12 condyloma/mild dysplasia biopsy specimens, and in 12 of
      13 moderate/severe dysplasia biopsy specimens. Polymerase chain reaction using
      HPV L1 consensus sequence primers followed by filter hybridization of the
      amplification products was positive for HPV DNA in two of 20 normal/squamous
      metaplasia biopsy specimens, in 23 of 76 HPV equivocal biopsy specimens, in eight
      of 12 condyloma/mild dysplasia biopsy specimens, and in 12 of 13 moderate/severe
      dysplasia biopsy specimens. Among biopsies that tested positive by polymerase
      chain reaction but that were negative by in situ hybridization, the most commonly
      identified HPV was type 16. We conclude that although HPV equivocal biopsy
      specimens contain HPV DNA more frequently than histologically normal tissue, the
      majority of biopsy specimens in this category test negative for HPV DNA. The
      clinical significance of a positive test for HPV, in the absence of unequivocal
      histologic changes, remains to be determined.

PMID- 8253457
TI  - Pancreatic xanthomatous neuropathy associated with hyperlipidemia: a cause of
      abdominal pain mimicking chronic pancreatitis.
AB  - "Hyperlipidemic crisis" is a term used to describe episodic abdominal pain in
      patients with hyperlipidemia. The morphologic correlates of this phenomenon have
      not been investigated and the etiology of the disorder is uncertain. We report a
      unique histologic finding in the pancreas of a 34-year-old woman with a 17-year
      history of episodic abdominal pain, sometimes accompanied by hyperamylasemia. At
      the age of 18 years, grossly elevated cholesterol and triglyceride levels were
      documented and type V hyperlipidemia was diagnosed. At the age of 34 years,
      subtotal pancreatectomy was performed for intractable abdominal pain. Histologic
      examination identified an increased number of enlarged pancreatic nerves that
      were infiltrated by foamy macrophages and encircled by fibrous tissue;
      endoneurial infiltration with macrophages occasionally split nerves into
      individual fascicles. Otherwise, the pancreas had only minimal fibrosis,
      nesidioblastosis, mucinous metaplasia of some pancreatic ducts, and scattered
      small collections of chronic inflammatory cells, subtle features suggesting very
      mild chronic pancreatitis. We propose that this novel xanthomatous neuropathy
      mimicked pancreatitis and was one of the underlying pathophysiologic mechanisms
      of abdominal pain in this patient. Further studies are necessary to document the
      prevalence of this new entity in patients with hyperlipidemia and to correlate
      its occurrence with "hyperlipidemic crisis" in those individuals.

PMID- 8253458
TI  - Alveolar soft part sarcoma: an unusually long interval between presentation and
      brain metastasis.
AB  - While alveolar soft part sarcoma is an uncommon soft tissue tumor known for late
      metastases to lung, bone, and brain, and interval of 33 years between primary
      presentation and development of brain metastasis has not been described. We
      document a patient with a removal of an alveolar soft part sarcoma from the
      pectoralis major muscle at the age of 10 years, a lung metastasis at the age of
      31 years, and brain and renal masses at the age of 43 years. The patient received
      surgical resections each time, but never radiotherapy or chemotherapy. He is
      currently alive and well. Immunohistochemistry, karyotypic analysis, flow
      cytometry, and gene expression were analyzed on primary tumor and established
      cell cultures in the hopes of further elucidating the histogenesis of this
      unusual neoplasm.

PMID- 8253459
TI  - Differentiating malignant pleural mesothelioma from pulmonary adenocarcinoma.

PMID- 8253460
TI  - The acquired immunodeficiency syndrome and the evolution of new micro-organisms:
      a pathologist's view.

PMID- 8253461
TI  - Chondroblastoma.
AB  - Chondroblastoma of the bone is a benign tumor that has well-characterized
      radiographic and histologic features. It tends to affect the epiphyseal ends of
      long bones in men during the second and third decades of life. The tumor is
      located more frequently at other sites in older patients. The treatment of choice
      is complete curettage with bone grafting, which in our series provided local
      control in 82% of patients at 2 years' follow-up. Recurrent tumors usually can be
      treated in the same manner.

PMID- 8253462
TI  - Thymoma--morphologic subclassification correlates with invasiveness and
      immunohistologic features: a study of 122 cases.
AB  - We applied the classification system of Marino and Muller-Hermelink (Virchows
      Arch A Pathol Anat Histopathol 407:119-149, 1985) and Kirchner and Muller
      Hermelink (Prog Surg Pathol 10: 167-189, 1989) to 122 thymic epithelial tumors to
      evaluate the utility of this classification and to determine its correlation with
      invasiveness, follicular lymphoid hyperplasia, myasthenia gravis, and
      immunophenotype. The majority of cases could be classified according to this
      scheme: eight cases (7%) were medullary thymoma, 34 cases (28%) were mixed
      thymoma, 20 cases (16%) were predominantly cortical (organoid) thymoma, 22 cases
      (18%) were cortical thymoma, 32 cases (26%) were well-differentiated carcinoma
      (WDC), two cases (2%) were high-grade carcinoma, and four cases (3%) were
      unclassifiable. We report a detailed histologic analysis of these subtypes, with
      criteria for diagnosis. We propose that the term "organoid thymoma" be replaced
      by "predominantly cortical thymoma." We also observed a previously unrecognized
      subtype of WDC with spindle-shaped epithelial cells, which must be distinguished
      from medullary thymoma. There was a strong correlation between histologic subtype
      and invasion (P < .0001). All medullary and mixed thymomas were either completely
      encapsulated (64%) or had only invasion through the capsule (36%). Organoid and
      cortical thymomas showed an intermediate degree of invasiveness, with 36%
      invasive into mediastinal fat and 14% into adjacent structures. All the cases of
      WDC were invasive either through the capsule (19%) or into adjacent structures
      (81%); five cases (16%) also showed distant spread in the form of pleural seeding
      (four cases) or lymph node metastasis (one case). Microscopic evaluation
      disclosed invasion in a substantial number of cases (28.5%) thought by the
      surgeon to be encapsulated. The presence of follicular lymphoid hyperplasia,
      either within the tumor, in the residual normal thymus, or in both, was a
      significant predictor of myasthenia gravis (P < .0015); there was an increased
      association of myasthenia gravis and thymomas with cortical type epithelium
      (organoid thymoma, cortical thymoma, and WDC). There was no correlation between
      epithelial cell morphology and antigen expression; however, the immunophenotype
      of the associated lymphocytes corresponded closely to the morphologic
      classification of the thymomas. The Muller-Hermelink morphologic classification
      can be applied to most cases of thymoma and strongly predicts invasive behavior.
      The correlation of lymphocyte immunophenotype with the morphologic classification
      of the epithelial cells suggests that it is biologically accurate.

PMID- 8253464
TI  - Rejection-independent cholangitis and cirrhosis following orthotopic liver
      transplantation.
AB  - The histologic diagnosis of extrahepatic biliary obstruction in the setting of
      orthotopic liver transplantation (OLT) may be complicated by nonobstructive
      factors, such as rejection, preservation injury, drug effects, and infection.
      Indeed, biopsy specimens from OLT patients frequently exhibit early
      posttransplant cholestasis, which is likely the result of several of these
      factors acting in concert. We reviewed the clinicopathologic features of 14 OLT
      patients whose biopsy specimens displayed prominent cholangitis with
      "obstructive"-type features. Cholangiograms, Doppler ultrasound examinations, and
      bacterial cultures were obtained in conjunction with all biopsy specimens.
      Despite histologic evidence of biliary obstruction, cholangiography revealed
      obstruction in only one case, leaks in four cases, and nine normal studies. Ten
      patients had severe systemic bacterial or cytomegalovirus infections. Biliary
      infection was documented in two cases. Hepatic artery occlusion was diagnosed in
      one case. The cholangitic pattern persisted in patients with unremitting
      infections, and two patients developed secondary biliary cirrhosis despite having
      consistently normal cholangiograms. Features of acute rejection or viral
      hepatitis were not observed on any biopsy specimen. The presence of this
      clinicopathologic spectrum was associated with a poor prognosis. Nine patients
      died and only four patients who responded to antibiotics survived. These findings
      demonstrate a striking cholangitic response to systemic infections in OLT grafts.
      The diagnosis of biliary obstruction in OLT liver biopsy specimens cannot be
      rendered without cholangiographic verification.

PMID- 8253463
TI  - Tracheobronchial AL amyloidosis: histologic, immunohistochemical,
      ultrastructural, and immunoelectron microscopic observations.
AB  - We have studied three cases of localized amyloidosis in the lower respiratory
      tract. Amyloid was nodularly or diffusely deposited in the lamina propria of the
      tracheobronchial mucosa. Its nature was confirmed by Congo red staining with
      green birefringence on polarized microscopy. "Tracheobronchopathia osteoplastica"
      also was demonstrated. Plasma cells and lymphocytes were scant in the amyloid
      mass. Few fibroblasts and even fewer macrophages were seen. The number of plasma
      cells was not increased in the bone marrow in any of our cases. Amyloid fibrils
      were demonstrated by electron microscopic examination. The amyloid P component
      was detected by immunohistochemical methods. The precursor protein of amyloidosis
      was shown to be amyloid L protein by the postembedding protein-A gold technique
      with anti-light chain antisera. The role of the plasma cells in amyloid
      formation, however, could not be ascertained. Based on these observations,
      amyloid fibril formation in tracheobronchial amyloidosis appears to be related to
      light chains secreted by local plasma cells, combined with amyloid P, calcium,
      and other factors.

PMID- 8253465
TI  - Health promotion for child survival in Africa: implications for cultural
      appropriateness.

PMID- 8253466
TI  - [Comic books and prevention of STD and AIDS. Critical analysis of 7 documents].

PMID- 8253467
TI  - Mobilizing support to strengthen the role of schools in preventing HIV infection,
      STD and other significant health problems.

PMID- 8253468
TI  - Strengthening the role of schools in preventing HIV infection, STD, and other
      important health problems.

PMID- 8253469
TI  - Developing and implementing school policies to address HIV infection and other
      health policies.

PMID- 8253470
TI  - Developing and implementing curricula to address HIV infection and other
      important health problems.

PMID- 8253471
TI  - Preparing school personnel to address HIV infection.

PMID- 8253472
TI  - Developing and implementing school health services to address HIV/AIDS.

PMID- 8253473
TI  - IUHPE global development. International Union for Health Promotion and Education.

PMID- 8253474
TI  - Encouraging health professionals to be effective health educators.

PMID- 8253475
TI  - [Current problems in drinking water hygiene].

PMID- 8253476
TI  - [Occurrence and detection of viruses in drinking water].
AB  - Viruses can pass disinfection steps of water treatment plants without being
      inactivated. Investigations during the last 15 years revealed repeatedly the
      presence of enteric viruses in finished water meeting standards for coliform
      bacteria. Methods for the detection of viruses in water which implicate their
      growth on specific cell cultures are very time consuming and do not cover many
      viral species. Molecular detection methods including PCR techniques may help in
      the development of alternate methods for virus detection particularly in drinking
      water which usually does not contain PCR inhibiting factors.

PMID- 8253477
TI  - [Mycobacteria in the environment].
AB  - Mycobacteria typically are free-living environmental saprophytes and strict
      pathogens such as M. tuberculosis and M. leprae, which do not proliferate in the
      inanimate environment form rare exceptions within the genus Mycobacterium. Many
      free-living mycobacteria such as M. avium and M. kansasii have been described as
      potential human pathogens and there is evidence that they are usually transmitted
      by inhalation, inoculation and ingestion from environmental sources. Soil, bogs,
      surface water, ground water and sea water have been described as natural habitats
      of environmental mycobacteria. In addition, artificial habitats such as tap water
      and sewage sludge are colonized by a considerable spectrum of mycobacterial
      species. Aquatic mycobacteria tend to colonize biofilms at air-water and solid
      water interfaces and the latter seem to be an important proliferation site in
      oligotrophic habitats. Outside the host tissue M. chelonae ssp. abscessus, M.
      kansasii, M. simiae, and M. xenopi have so far almost exclusively been isolated
      from artificial oligotrophic aquatic habitats, i.e. tap water and drinking water;
      their natural reservoir is unknown. Some species have not yet been isolated from
      the environment although epidemiological data suggest that infections caused by
      these organisms are acquired from environmental sources.

PMID- 8253478
TI  - [Drinking water and parasites].
AB  - Entamoeba histolytica, Giardia lamblia, Cryptosporidium parvum, Isospora belli,
      Balantidium coli, and Microsporidia spp. are cosmopolitan parasites. They often
      cause diarrheal diseases. The waterborn transmission of all these parasites is
      possible (41). Surface water supplies used for drinking water are potential
      sources of contamination. Giardia lamblia and Cryptosporidium spp. have received
      great attention in industrialized countries during the last years because they
      are the etiological agents of waterborne diseases. The life cycles of Giardia
      lamblia and Cryptosporidium are described with a special reference to drinking
      water technologies aimed at removing these parasites.

PMID- 8253479
TI  - [Health hazards from metals in drinking water].
AB  - Drinking water is essential for man and cannot be replaced. In the public
      discussion the quality of drinking water is often presented in a one-sided way.
      This has led to great sensitivity and insecurity with the result that the intake
      of drinking water is often regarded as deleterious to human health. In this
      presentation it is attempted to demonstrate by the example of six metals and semi
      metals in which way these substances are transmitted into water, how much the
      consumption of drinking water contributes to the total uptake, and whether a
      health risk can be derived from this source.

PMID- 8253480
TI  - [New vaccines in the age of genetic engineering].
AB  - The era of genetic engineering is merely 20 years of age, yet has already borne
      completely new perspectives for vaccine development. Important insights are
      gained by elucidating the genetic information of a disease-causing microorganism
      and its pathogenic and attenuated variants. Site-directed mutagenesis can then be
      employed to specifically alter the genetic information in a variety of ways. Upon
      transfer of the corresponding gene to pro- or eucaryotic cells, large quantities
      of microbial components can be produced. A new generation of such subunit
      vaccines is already undergoing clinical testing. Recently, hybrid vaccines have
      been constructed, which utilize highly successful traditional live vaccines such
      as polio- and vaccinia-virus or the Tbc-bacterium as carriers for components of
      other microorganisms. We should bear in mind that the same new technologies can
      be abused for the construction of potentially dangerous biological weapons. The
      scientific community bears the responsibility to prevent such abuse and to lobby
      for an easy access to the new vaccines by the world's poorest inhabitants.

PMID- 8253481
TI  - [International AIDS Congress; Berlin, June 7-11, 1993].

PMID- 8253482
TI  - Adolescence--the forgotten and neglected opportunity.

PMID- 8253483
TI  - Unnecessary injections and poliomyelitis.

PMID- 8253484
TI  - Establishing a new pediatric intensive care unit.
AB  - Pediatric intensive care is a collaborative practice of dedicated personnel,
      advanced technology and a diverse group of support services. Unit design must
      focus on current patient needs while envisioning the technological and clinical
      needs of the future. With insight and a cooperative effort, your design team can
      effectively transform ideas into a unit committed to the care of critically ill
      children.

PMID- 8253485
TI  - Pediatric cardiopulmonary resuscitation: review and update of advanced life
      support.

PMID- 8253486
TI  - Acid-base disorders in the critically ill child.

PMID- 8253487
TI  - Cardiogenic shock in the neonate.
AB  - The neonate with circulatory failure and cardiogenic shock is a difficult
      management problem. However, the initial approach is that of resuscitation with
      exact diagnosis of secondary concern. Once the infant has been stabilized and
      septic and hypovolemic shock have been excluded, attention should be directed to
      the four most likely causes of cardiogenic shock: structural heart disease with
      left heart obstruction being the most common, cardiac muscle disorders, cardiac
      dysrhythmias, and cardiac metabolic disorders.

PMID- 8253488
TI  - Cardiac dysrhythmias in pediatric intensive care.

PMID- 8253489
TI  - Neurointensive care in children.

PMID- 8253490
TI  - Brain stem electric response audiometry in neonates with hyperbilirubinemia.
AB  - Auditory evoked responses using BERA were studied in 30 newborn babies with
      plasma bilirubin > or = 15 mgm/dl and repeated after treatment of neonatal
      jaundice with bilirubin levels of < or = 10 mgm/dl. A few jaundiced babies
      (16.5%) showed absent BERA response at the initial/subsequent examination. After
      treatment, 3/30 babies showed absent wave form responses and 2 of these were
      clinically kernicteric. Jaundiced babies had prolonged wave peak latencies and
      inter peak latencies. Treated babies showed a tendency towards recovery in their
      BERA responses which were however not complete. Total plasma bilirubin value at
      the time of BERA examination and mean maximal bilirubin values had no correlation
      with the incidence and degree of BERA abnormalities.

PMID- 8253491
TI  - Trends in neonatal outcome with low Apgar scores.
AB  - Trends in incidence and neonatal outcome following low Apgar scores (1 min Apgar
      score < 6) were prospectively studied during the years (1981, 1983, 1986 and
      1988. The incidence of birth asphyxia was 7.6% of live births during the study
      period; it was 5.8% in 1981, increased to highest of 8.9% in 1986 with slight
      reduction to 7.2% in 1988. Birth weight distribution of asphyxiated babies and 1
      min Apgar score < 3 (severe asphyxia) remained unchanged. A significant decline
      in neonatal mortality with asphyxia was noted from 46.0% to 28.4% during 1981 and
      1988 respectively. Aetiological factors for asphyxia could be identified in
      nearly 90% of infants during 1988, and all but 2 of 12 factors studied registered
      significant differences from control non-asphyxiated group.

PMID- 8253492
TI  - Evaluation of BR-16 A (Mentat) in cognitive and behavioural dysfunction of
      mentally retarded children--a placebo-controlled study.
AB  - It is important to control abnormal behaviour and hyperactivity, and improve
      cognition in mentally retarded children (MRC), which would help in their
      education, training and subsequent rehabilitation. Recently it has become known
      that amongst other side-effects, protracted use of anti-convulsant medication
      induces cognitive and behavioural dysfunction, which is a major problem in
      mentally retarded epileptics. In a placebo-controlled study, we confirmed the
      efficacy of a herbal preparation, BR-16A (Mentat) in controlling such behavioural
      and cognitive deficits in 40 mentally retarded children. The efficacy of this
      remedy was further evaluated in 19 MRCs with epilepsy. Twelve patients had
      generalised seizure, 4 with partial and 3 with mixed seizure pattern was
      continued. Inspite of the usual antiepileptic treatment, the frequency of
      seizures ranged from 1 to 7 attacks in periods from 1 week to 1 year. With active
      drug Br-16A, it was possible to note a reduction in seizure frequency. Patients
      with higher frequency responded better. There was no further increase in the
      dosage of antiepileptic drugs. There was significant control of other abnormal
      behaviour as shown by reduction in rating score on the Children's Behavioural
      Inventory test. BR-16A was effective in controlling abnormal behaviour,
      especially hyperactivity and incongruous behaviour in mentally retarded children
      with and without epilepsy.

PMID- 8253493
TI  - Mother surrogate and nutritional status of preschool children.
AB  - The study was conducted on 200 preschool children to find out the effect of
      mother surrogate on the nutritional status. The nutritional status of children
      was found to be affected by the time devoted by mother on child care activities,
      working status of mother and type of family independently and jointly. The
      children cared by mother had better nutritional status than those children who
      were cared by servants and any other family member in the absence of mother. It
      shows that no one can substitute the care provided by the mother.

PMID- 8253494
TI  - Optimum needle length for DPT inoculation of Indian infants.
AB  - Correct placement of the injected DPT vaccine into the deep muscular layers
      decreases the local reactions, including the sterile abscess formation. However,
      recommendations on size of the needle to be used and the angle of injection are
      not easily available, are not uniform and are based on case reports. The only
      study based on scientific data of ultrasonographic measurement of fat layer and
      muscle layer thickness of thigh of only 24 infants of 4 months age covers only
      American children. (Hick et al, Pediatrics 1989; 84: 136-37). In the present
      study, we have produced similar data on 215 Indian children belonging to all
      those age groups in which DPT vaccinations are given. Mean thickness of skin +
      fat layer in the middle one-third of the anterolateral aspect of thigh was 1.03
      +/- 0.23 cm, 1.04 +/- 0.21 cm, 0.95 +/- 0.19 cm and 1.06 +/- 0.27 cm in the age
      groups of 6-12 weeks (Groups I), 13-18 weeks (Group II), 19-24 weeks (Groups III)
      and 18 +/- 1 month (Group IV) respectively. These age groups correspond to the
      timings of first 3 primary doses and the first booster dose of the DPT vaccine in
      our immunization clinic. Mean thickness of all the soft tissues together at the
      same site were 1.87 +/- 0.35, 2.17 +/- 0.38, 2.07 +/- 0.39 and 2.07 +/- 0.26 cm
      respectively for the groups I to IV.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253495
TI  - Hereditary factor XIII deficiency.
AB  - Twelve cases of hereditary factor XIII (FX III) deficiency diagnosed over five
      years (1986-1990) at Christian Medical College and Hospital, Vellore are
      presented here. Although all the cases had a history of umbilical cord bleeding
      and subsequent frequent bleeding episodes, diagnosis was considerably delayed.
      All but two patients required transfusions for bleeding episodes. Ten patients
      had a history of consanguinity in parents. Clinical features and family history
      are described in detail here. The ease of performing the Urea solubility test and
      problems in it's interpretation are highlighted. The role of prophylactic
      transfusion is also discussed.

PMID- 8253496
TI  - Hypothalamic hamartomas and precocious puberty.
AB  - Ten children, five boys and five girls with true precocious puberty at an early
      age were found to have hypothalamic hamartomas on brain imaging. Very early onset
      of puberty, varying from a few weeks to three years of age, and rapid progression
      were characteristic. Accelerated growth velocity and markedly advanced bone age
      were evident in all. Gonadotropin and gonadal hormone levels were elevated above
      the prepubertal range. Six children had associated developmental delay or
      hyperactivity.

PMID- 8253497
TI  - Unnecessary injections given to children under five years.
AB  - Adults accompanying 64 children attending a hospital out-patient clinic were
      questioned about treatment and injections given for illnesses in the previous
      month. Half the children had received injections, almost all given by private
      doctors: we consider most of these injections to have been unnecessary. Three
      girls were paralysed by aggravation poliomyelitis after unnecessary injections.
      Adults approved of injections although they did not know what was injected.

PMID- 8253498
TI  - Intraperitoneal red currant jelly in intussusception.

PMID- 8253499
TI  - Hepatic perforation due to ascariasis.

PMID- 8253500
TI  - Familial porencephaly.

PMID- 8253501
TI  - Xanthogranulomatous pyelonephritis.

PMID- 8253502
TI  - Prophylaxis of febrile convulsions--is it indicated?

PMID- 8253503
TI  - The pulse oximeter.

PMID- 8253504
TI  - Sex ratio and infant mortality rate.

PMID- 8253505
TI  - Campylobacter enteritis in Gujarat.

PMID- 8253506
TI  - Small airways function in aluminium and stainless steel welders.
AB  - The effect of welding fumes on small airways was studied in 25 male subjects who
      welded in aluminium (Al) and to some extent also in stainless steel (SS). Despite
      a low exposure to welding fumes as compared to the permissible exposure limits,
      excretion of Al in urine was found to be increased in all subjects (median value:
      0.29 mmol/mol creatinine on Friday afternoon, as compared to an upper reference
      level of 0.10 mmol/mol creatinine). In addition, the welders displayed increased
      prevalences of work-related eye and airways (pharyngitis and non-specific
      bronchial hyperreactivity) symptoms, as compared to 25 matched controls. Short
      term welders (< or = 2.5 years) had more symptoms related to the upper airways
      than did long-term welders, which may indicate a selection. Spirometry, closing
      volume and volume of trapped gas (VTG) did not deviate. However, after
      methacholine inhalation, the long-term welders had a significantly steeper slope
      of the alveolar plateau on the single-breath nitrogen wash-out test, and a slight
      increase in VTG, as compared to the short-term welders and the controls. These
      findings may indicate a welding fume-induced increase in the reactivity of the
      small airways. Because Al welding was far more frequent than SS welding, an
      association with the former seems likely.

PMID- 8253507
TI  - Effects of aircraft noise on hearing and auditory pathway function of school-age
      children.
AB  - This study was conducted to investigate the influence of high-frequency aircraft
      noise on the function of the auditory system of school-age children. A total of
      228 students attending a school near an airport (school A) and 151 students
      attending a school far from an airport (school B) were analyzed. Audiometry and
      brainstem auditory evoked potential (BAEP) detection were performed in all
      subjects to evaluate cochlear and retrocochlear function. The results of
      audiometry indicated that hearing ability was significantly worse in the children
      of school A, which was located under the flight paths. The values of pure tone
      average, high pure tone average, and threshold at 4 kHz were all higher in
      children who were frequently exposed to aircraft noise. There was no consistent
      difference in BAEP latencies between the two schools. These results indicate that
      central transmission is not affected in children who have been exposed to
      aircraft noise for several years. The results of the present study showed a
      significant association between aircraft noise exposure and prevalence of noise
      induced hearing loss. Although damage to peripheral cochlear organs was confirmed
      in school-age children, involvement of the central auditory pathway could not be
      verified.

PMID- 8253508
TI  - Trichothecene mycotoxins in the dust of ventilation systems in office buildings.
AB  - Analysis of trichothecene mycotoxins in dust samples from ventilation systems of
      office buildings was applied as a rapid and inexpensive method for the detection
      of mycotoxins. Dust samples from three different office spaces of the Montreal
      urban area, reportedly affected by the "sick buildings syndrome", were analysed
      by thin-layer chromatography (TLC). Positive colour reaction on TLC plates with 4
      (p-nitrobenzyl) pyridine, specific for the 12,13-epoxy group in the trichothecene
      nucleus, was obtained for the extracts of 0.5- to 50-g dust samples. The dust
      samples contained at least four trichothecenes: T-2 toxin, diacetoxyscirpenol,
      roridine A and T-2 tetraol. The results were confirmed by high-performance liquid
      chromatography analysis. Screening of dust samples from air ventilation systems
      of reportedly affected buildings provided direct evidence of trichothecene
      mycotoxins, with the detection limit estimated as 0.4-4 ng/mg dust. Thus, the
      dust sample analysis is suggested as a rapid technique for detecting the presence
      of myotoxins in the dust of ventilation systems.

PMID- 8253509
TI  - Comparison of blood pressure in deaf-mute children and children with normal
      hearing: association between noise and blood pressure.
AB  - The present study assessed the relationship between noise exposure and blood
      pressure. The study population consisted of 892 children from two elementary
      schools. The noise-sensitive group comprised 583 subjects with normal hearing
      from one school, while the noise-insensitive group comprised 309 deaf-mutes from
      another school. The deaf subjects had significantly lower blood pressure than the
      subjects with normal hearing (P < 0.05) after adjustment for age. Multiple
      regression analysis revealed that body mass index, age, and hearing ability
      explained a significant amount of the variation in systolic and diastolic blood
      pressure (R2 = 0.17 and 0.16, respectively). On the basis of the results, it is
      suggested that noise exposure is associated with higher systolic and diastolic
      blood pressure.

PMID- 8253510
TI  - Blood styrene concentrations in a "normal" population and in exposed workers 16
      hours after the end of the workshift.
AB  - Blood styrene was measured by a gas chromatography-mass spectrometry method in 81
      "normal people" and in 76 workers exposed to styrene. In the normal subjects,
      styrene was also tested in alveolar and environmental air. Styrene was found in
      nearly all (95%) blood samples. Average styrene levels in the normal subjects
      were 221 ng/l in blood (Cb), 3 ng/l in alveolar air (Ca) and 6 ng/l in
      environmental air (Ci). Styrene levels did not differ significantly between
      smokers and nonsmokers, 95% of values being below 512 ng/l in Cb, 7 ng/l in Ca
      and 15 ng/l in Ci. In workers with an average exposure to styrene of 204
      micrograms/l, at the end of the workshift, mean blood styrene concentration was
      1211 micrograms/l. In blood samples collected at the end of the Thursday shift,
      styrene levels were significantly higher (1590 micrograms/l) than those found at
      the end of the Monday shift (1068 micrograms/l). A similar difference was found
      in samples taken the morning after exposure (60 and 119 micrograms/l,
      respectively). Significant correlations between blood and environmental styrene
      were found both at the end of the shift and the morning after exposure (r = 0.61
      and 0.41, respectively). In workers occupationally exposed to styrene, 16 h after
      the end of the workshift, blood styrene (94 micrograms/l) was significantly
      higher than that found in the normal subjects (0.22 microgram/l). The half-life
      of blood styrene was 3.9 h.

PMID- 8253511
TI  - Urinary excretion of homovanillic acid in workers exposed to manganese.
AB  - Homovanillic acid, an end product of dopamine catabolism, and manganese (Mn) were
      measured in the urine of 68 male workers exposed to Mn-containing dust in a dry
      alkaline battery plant or an Mn oxide and salt producing plant, and in 35 control
      male subjects. The geometric mean of the airborne concentration of inhalable
      (total) dust amounted to 0.95 and 1.37 mg/m3 in the dry alkaline battery plant
      and the Mn oxide and salt producing plant, respectively. In the latter, a higher
      prevalence of increased values of urinary homovanillic acid concentration was
      found. In the total population, there was a low but statistically significant
      positive correlation between the concentration of homovanillic acid and Mn in
      urine (r = 0.20, P = 0.04) but there was no significant correlation between the
      level of homovanillic acid in urine and Mn in airborne dust or duration of
      exposure. This observation might be compatible with the stimulation of dopamine
      turnover in the brain, which has been observed in the early phase of Mn
      intoxication in animals. However, the large variability in urinary homovanillic
      acid excretion in control subjects precludes the use of this biological indicator
      to detect early interference of Mn with the dopaminergic system.

PMID- 8253513
TI  - Occupational-type exposure tests and bronchoalveolar lavage analyses in two
      patients with byssinosis and two asymptomatic cotton workers.
AB  - Two workers suffering from stage III byssinosis and claiming for compensation
      were examined. Bronchial obstruction was present in one case. MEF25-75 values
      were significantly reduced and bronchial hyperreactivity was present in both
      subjects. Occupational-type exposure tests with cotton dust resulted in
      significant decreases in arterial oxygen pressure for more than 2 h and were
      associated with an obstructive ventilation pattern in one of the patients.
      Prolonged hypoxemia which is not paralleled by lung function changes is probably
      typical for byssinosis patients since we have never seen this in inhalative
      challenge tests with various environmental antigens and other occupational
      substances including flour dust. No specific IgE or IgG antibodies could be
      detected. In the two patients a hitherto unknown significant increase in CD23+
      lymphocytes and granulocytosis were detected by bronchoalveolar lavage (BAL).
      Corresponding investigations in two cotton workers without any evidence of
      byssinosis revealed neither lung function changes after the exposure test nor
      striking BAL findings. Our results demonstrate the diagnostic value of specific
      challenge tests and BAL investigations in patients suffering from byssinosis,
      which is often difficult to diagnose.

PMID- 8253512
TI  - Organic dust disease of airways.
AB  - Exposure to aerosols of organic dusts such as coffee, tea, spices, soy, fur, and
      animal food in an occupational setting can affect the respiratory health of
      industrial workers. Based on our experience with workers from many small
      industries processing organic materials, we discuss the clinical features and
      possible mechanisms responsible for the respiratory impairment associated with
      these types of dust exposure. Significantly higher prevalences for most chronic
      respiratory symptoms were found among exposed workers than among control workers.
      Smoking appears to aggravate these symptoms. A large number of exposed workers
      complained of acute symptoms which developed during the work shift. In exposed
      workers, significant across-shift reductions in lung function were recorded for
      all spirometric tests, but particularly for the flow rates at 50% and 25% of
      vital capacity on maximum expiratory flow-volume curves. Comparison of preshift
      measured ventilatory capacity tests with predicted normal values indicates that
      these workers demonstrate obstructive changes affecting primarily flow rate at
      low lung volumes. The data suggest that exposure to organic aerosols in
      industrial settings, particularly in conjunction with smoking, may be associated
      with the development of chronic obstructive lung disease.

PMID- 8253514
TI  - A novel technique for the detection of DNA single-strand breaks in human white
      blood cells and its combination with the unscheduled DNA synthesis assay.
AB  - A modified assay for the detection of DNA single-strand breaks (SSBs) in human
      mononucleated white blood cells (MWBCs) based on the nick translation (NT)
      reaction was developed and combined with the test for unscheduled DNA synthesis
      (UDS). Both assays were performed on disposable 96-well filtration plates and
      therefore allowed rapid and sensitive examination of SSBs and UDS. Only 5-8 ml of
      heparinized blood is required for an eightfold determination in both assays. The
      uptake of radioactive nucleotide precursors was demonstrated to depend linearly
      upon the NT reaction time and in both assay systems on the number of investigated
      cells. The best results and the lowest signal to noise ratio were obtained when
      the NT assay was performed at 25 degrees C for 20 min. The test was standardized
      for 150,000 MWBCs/well and a polymerase I concentration of 20 U/ml. The same
      number of cells were used to measure UDS during a 4-h incubation at 37 degrees C.
      We observed a dose-dependent increase in SSBs after in vitro incubation with N
      methyl-N-nitrosoguanidine (MNNG), with a detection limit of 50 microM when MNNG
      was present for 1 h and of 5 microM after 20-h incubation period. UDS in MWBCs
      was increased after treatment for 1 h with MNNG (200 microM) only if
      poly(ADP)ribose synthesis was inhibited by 3-aminobenzamide. UDS was induced by
      320 microM methyl methanesulfonate, but SSBs could only be detected after
      inhibition of UDS by 100 microM hydroxyurea.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253515
TI  - Detection of DNA single-strand breaks in lymphocytes of smokers.
AB  - In a controlled study, ten male volunteers (five smokers and five nonsmokers)
      were subjected to different smoking conditions and compared to five nonsmokers,
      not exposed to cigarette smoke. During the 4 days of the study, nonsmoking
      periods were strictly controlled. On the first day the ten subjects were sham
      exposed. On the second day the five smokers smoked 24 cigarettes in 8 h, while
      the five nonsmokers were exposed to the environmental tobacco smoke. After
      another day of sham exposure the smoke exposure was repeated under the same
      conditions. Blood was drawn before and after exposure and DNA single-strand
      breaks (SSBs) were analyzed in lymphocytes immediately (1 h) after isolation of
      cells and after 4 h incubation at 37 degrees C, using a modified assay based on
      the nick translation reaction. Base levels of unscheduled DNA synthesis (UDS) and
      UDS levels were determined after 1 h incubation with methyl methanesulfonate.
      Duplicate analysis using the same method was performed in a second laboratory
      after transportation of blood samples at 0 degree C on a train from Munich to
      Hamburg. Tobacco smoke exposure of the subjects increased COHb and plasma
      cotinine levels. SSBs could be detected in all probands with some interindividual
      day-to-day and morning-to-evening variations. In four of five active smokers, SSB
      increases were found after smoking. In nonsmokers exposed to tobacco smoke no
      exposure-related variation in SSB levels could be detected.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8253516
TI  - Biological monitoring of styrene in the reinforced plastics industry in Emilia
      Romagna, Italy.
AB  - Biological monitoring of styrene exposure among workers in the reinforced
      plastics industry is widely implemented in the region of Emilia Romagna, Italy.
      More than 18,000 urine samples measurements of the main metabolites of styrene,
      mandelic (MA) and phenylglyoxylic acid, were retrieved for the period 1978-1990,
      and 4689 values of MA in postshift urine samples were analyzed for various
      variables thought to influence styrene exposure. The job performed was found to
      be the most important predictor of styrene exposure. Hand laminators had the
      highest exposure (mean MA 682 mg/g creatinine); spray laminators showed lower
      values (404 mg/g), while levels in semiautomatic process operators (243 mg/g)
      were only slightly higher than in nonprocess workers (186 mg/g). The use of
      ventilation resulted in lower exposure, but differences in average values were
      not particularly wide. Exposure decreased weakly during the study period in all
      work categories, but the percentage of measurements exceeding the current
      biological limit value (900 mg/g creatinine, 1300 mg/l corrected for density) is
      still very high (20% of measurements among hand laminators in 1990). These
      results indicate that the control measures implemented are only partially
      effective for the prevention of styrene exposure.

PMID- 8253517
TI  - Biological monitoring of occupational exposure to toluene diisocyanate.
AB  - The study validated the use of urinary toluene diamine (TDA) in postshift samples
      as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine
      workers exposed in TDI-based polyurethane foam production were studied. Their
      exposure levels varied in 8-h time-averaged samples from 9.5 to 94 micrograms/m3.
      The urinary TDA concentrations varied from 6.5 to 31.7 micrograms/g creatinine
      and they were linearly related to the atmospheric TDI levels. Approximately 20%
      of TDI is metabolized to diamines but their specificity is remarkable to the
      extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the
      percutaneous absorption may be had.

PMID- 8253518
TI  - Regulation of melanoma-cell motility by the lipoxygenase metabolite 12-(S)-HETE.
AB  - Cellular motility, a prerequisite for metastasis of tumor cells, is affected by a
      55-kDa tumor-cell-secreted cytokine which influences the migration of the
      producing cells and is called autocrine motility factor (AMF). Previous studies
      indicated that AMF stimulates motility by binding to its receptor, a cell-surface
      glycoprotein of 78 kDa (gp78), inducing its phosphorylation, activating a
      pertussis toxin (PT)-sensitive G-protein, and stimulating inositol metabolism.
      However, the intracellular signaling mechanisms which transduce and regulate the
      AMF motility response remain largely unknown. 12-(S)-HETE, a lipoxygenase
      metabolite of arachidonic acid which affects the cytoskeletal architecture of
      murine melanoma cells, also stimulates cell motility independently of PT
      sensitive G-proteins and up-regulates gp78 surface expression. 12-(S)-HETE
      induces the phosphorylation of gp78 in a manner analogous to AMF and the motility
      response of these murine melanoma cells to both AMF and 12-(S)-HETE is inhibited
      by protein kinase C inhibitors. Furthermore, perturbation of the AMF receptor
      stimulated endogenous biosynthesis of 12(S)HETE. These results suggest the
      existence of an "autocrine motility cycle" which influences melanoma cell
      motility by gp78 activation, and production of second messengers which affect the
      cytoskeletal architecture and expression of the AMF receptor itself.

PMID- 8253519
TI  - Chemoprevention by indomethacin of tumor promotion in a rat urinary bladder
      carcinogenesis model.
AB  - The chemopreventive effects of indomethacin (IM) on the enhancement of bladder
      carcinogenesis and transitional-epithelial-cell proliferation by butylated
      hydroxyanisole (BHA) or sodium L-ascorbate (Na-AsA) were investigated. All
      animals were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their
      drinking water for 4 weeks. They then received 2% BHA or 5% Na-AsA for 20 weeks,
      followed by 20 ppm IM in the drinking water or normal tap water without
      supplement for a further 20 weeks, or BHA or Na-AsA alone or concomitantly with
      IM for 40 weeks. No differences in bladder-tumor development were found when IM
      was administered after cessation of BHA or Na-AsA exposure. However, IM in
      combination with either BHA or Na-AsA significantly reduced both the incidence
      and the multiplicity of papillomas and carcinomas as compared with the values of
      groups receiving BHA or Na-AsA alone. This was associated with decreased DNA
      synthesis and prostaglandin (PG) E2 levels in the existing bladder tumors.
      Combined treatment with IM did not exert any effects on BHA forestomach
      carcinogenesis. A separate 8-week combination study demonstrated that IM
      diminished the increase in expression of proliferation nuclear-cell antigen
      (PCNA) induced by BHA or Na-AsA alone. The present results suggest that PGE2 may
      be involved in promotion of rat bladder carcinogenesis and that the PG synthesis
      blocker IM might exert preventive effects on the development of bladder cancer in
      humans.

PMID- 8253520
TI  - Tamoxifen modulation of cisplatin cytotoxicity in human malignancies.
AB  - Recent clinical trials have indicated that addition of tamoxifen (TAM) to a
      combination of cisplatin (DDP), carmustine and dacarbazine markedly increases the
      overall objective response rate of patients with metastatic malignant melanoma.
      Previous studies have determined that there is remarkable synergy between TAM and
      DDP in a human melanoma cell line T-289. Using the technique of median effect
      analysis, in clonogenic assay, we observed a highly synergistic interaction
      between TAM and DDP. To determine whether or not this synergistic interaction was
      unique to human melanomas, or is generally observed in other types of malignancy,
      we examined the nature of this interaction using a human ovarian carcinoma and
      small cell lung cancer cell line. Synergy was observed in both cell lines. In the
      case of all 3 types of malignancy, synergy was observed at concentrations of both
      TAM and DDP that can be achieved in patients. Our results demonstrate that
      cytotoxic synergy between the DDP and TAM is observed in cell lines established
      from multiple types of human malignancies. It is important to note that the
      synergy between TAM and DDP is not dependent on the presence of estrogen or
      progesterone receptors. Since TAM is well tolerated by patients, it is
      particularly attractive as a potential agent with which to sensitize human tumors
      to DDP.

PMID- 8253521
TI  - Differences in cell surface carbohydrates, and in laminin and fibronectin
      synthesis, between adherent and non-adherent Ehrlich ascites tumor cells.
AB  - Differences in cell surface carbohydrates and in laminin and fibronectin
      synthesis between 2 Ehrlich ascites tumor (EAT) cell lines, the adherent and non
      adherent EAT cells, have been studied. The adherent EAT (a-EAT) cells grow in
      monolayer in vitro in the presence of fetal bovine serum. The classical, or non
      adherent EAT (na-EAT), cells grow in suspension in ascites form in the peritoneal
      cavity of mice, and they do not adhere when cultured in vitro. Both EAT cell
      lines express surface glycoproteins reactive with Maackia amurensis lectin (MAL)
      and Griffonia simplicifolia isolectin GS I-B4. However, only a-EAT cells react
      with elderberry (Sambucus nigra) bark lectin (SNA), suggesting that there are
      some differences in the sialylation of cell surface carbohydrate moieties between
      these 2 EAT cell lines. Removal of cell surface sialic acid by treating a-EAT
      cells with Vibrio cholerae neuraminidase did not abolish the ability of these
      cells to adhere to laminin- or fibronectin-coated plates, indicating that the
      sialic acid of the cell surface glycoproteins is not essential for their adhesion
      to these extracellular matrices. Therefore, the difference in sialylation of cell
      surface glycoproteins is not responsible for the difference in cell adhesion
      between these 2 lines of EAT cells. Both EAT cell lines express detectable
      amounts of laminin but not fibronectin on their surfaces; they both secrete
      fibronectin and entactin into the medium. The na-EAT cells (but not the a-EAT
      cells) also secrete laminin A chain into the culture medium; however, no B chain
      was detected in the culture medium of either cell line. The laminin isolated from
      the cell surface of na-EAT cells reacts with GS I and MAL lectins, but not with
      SNA, whereas the laminin isolated from a-EAT cells reacts with SNA, as well as GS
      I and MAL.

PMID- 8253522
TI  - Ability of the non-phorbol ester-type tumor-promoter thapsigargin to mimic the
      stimulatory effects of 12-0-tetradecanoylphorbol-13-acetate on ornithine
      decarboxylase activity, hydroperoxide production, and macromolecule synthesis in
      mouse epidermis in vivo.
AB  - The biochemical effects of the non-12-0-tetradecanoylphorbol-13-acetate (TPA)
      type tumor promoter thapsigargin (TG), which does not bind to the phorbol-ester
      receptor, or activate protein kinase C (PKC) or increase inositol polyphosphates,
      were characterized in mouse epidermis in vivo. The cold scraping method is
      required to detect the induction of ornithine decarboxylase (ODC) activity by TG,
      a response much smaller than that caused by TPA and with a different time course.
      TG pre-treatments do not alter or cause a refractory state against ODC induction
      by TPA. But TG stimulates hydroperoxide (HPx) production and RNA, protein, and
      DNA synthesis almost as much as TPA. Moreover, the sequential effects of TG and
      TPA on DNA synthesis are identical: early inhibition at 8 hr followed by maximal
      stimulation at 16-32 hr. TG-stimulated HPx production requires protein synthesis
      and xanthine oxidase, phospholipase A2, and lipoxygenase activities but not RNA
      and DNA synthesis, and cyclooxygenase and protease activities. The HPx response
      to TG is not mimicked by the PKC activator prostratin or inhibited by pre
      treatments with prostratin or specific PKC inhibitors. However, the Ca(2+)-ATPase
      inhibitor cyclopiazonic acid and the Ca2+ ionophore and weak ODC inducer A23187
      mimic remarkably the HPx responses to TG and TPA. Since TG and A23187 are known
      to be, respectively, weak and incomplete tumor promoters as compared with TPA,
      the present results suggest that the HPx responses common to Ca(2+)-mobilizing
      and TPA- or non-TPA-type agents are insufficient to achieve tumor promotion in
      the absence of major ODC induction.

PMID- 8253523
TI  - Immunohistochemical survey of pS2 expression in intraductal lesions associated
      with invasive ductal carcinoma of the breast.
AB  - We examined the expression of pS2 protein in 48 invasive ductal breast carcinomas
      with an extensive intraductal component, using immunohistochemical staining of
      paraffin-embedded sections. The patients selected for this study would have met
      the criteria for breast-conserving surgery applied at our institute at present.
      The rate of pS2 expression in the intraductal lesion was significantly higher
      than that in the main invasive lesion. The incidence of pS2 protein expression in
      the latter lesions was very similar to that in invasive carcinoma without
      intraductal lesions. The pS2 positivity of the intraductal lesion was equal to or
      higher than that of the invasive lesion. Of intraductal lesions, those classified
      as non-comedo carcinomas frequently contained more pS2 protein than did comedo
      carcinomas.

PMID- 8253525
TI  - Estimates of the worldwide mortality from eighteen major cancers in 1985.
      Implications for prevention and projections of future burden.
AB  - This report presents worldwide estimates of annual mortality from all cancers and
      for 18 specific cancer sites around 1985. Crude and age-standardized mortality
      rates and numbers of deaths were computed for 24 geographical areas. Of the
      estimated 5 million deaths from cancer (excluding non-melanoma skin cancer), 56%
      occurred in developing countries. The most frequent neoplasm is lung cancer,
      accounting for 22% of cancer deaths in men. Among women breast cancer is the
      leading malignancy, accounting for 16% and 11% of all cancer deaths in developed
      and developing countries, respectively. In developing countries, cancer of the
      cervix uteri ranks first, breast cancer second. The second most frequent cause of
      death from cancer in both sexes is cancer of the stomach, followed by liver
      cancer in men and by colon/rectum cancer in women. Cancers of the colon/rectum
      and prostate maintain a high rank in men living in developed countries, while
      cancers of the lung, ovary and pancreas occupy similar ranks among women. In
      developing countries, cancers of the oesophagus and mouth/pharynx follow those
      previously mentioned in both sexes. If the estimated rates continue to prevail,
      increases in the numbers of deaths of 20.4% in developed and 18.1% in developing
      countries are expected by the year 2000, simply as a consequence of demographic
      trends towards ageing and population growth. Our results provide an indication of
      the potential impact of preventive practices. It is estimated that 20% of all
      cancer deaths (1 million) could be prevented by eliminating tobacco smoking.
      Mortality from cancers of the liver and uterine cervix, both major problems in
      developing countries, could be substantially reduced by immunization against
      hepatitis B virus infection and early detection through Pap smears, respectively.

PMID- 8253524
TI  - Breath hydrogen and methane in populations at different risk for colon cancer.
AB  - Results from laboratory and clinical studies have suggested that fermentation in
      the large bowel may play a protective role against colon cancer. Hydrogen and
      methane are end-products of colonic fermentation that are absorbed into the
      bloodstream and excreted via expired air in the breath. Thus, breath levels of
      hydrogen and methane have been used as markers for this process. Breath levels of
      these gases were compared among 10 ethnic and sex groups that exhibit marked
      differences for colon cancer risk in Hawaii. Four end-expiratory breath samples
      were used to characterize daily excretion of hydrogen and methane in a population
      based sample of 244 men and women. There was no significant difference in breath
      hydrogen or methane by sex or age. Hawaiians produced significantly more hydrogen
      than Filipinos, and Hawaiians and Caucasians more methane than the 3 Asian
      groups. These differences did not correlate with risk of colon cancer among these
      ethnic populations.

PMID- 8253526
TI  - Association between expression of sialosyl-Tn antigen and intestinalization of
      gastric carcinomas.
AB  - We examined immunohistochemically the expression of sialosyl-Tn antigen (STN) in
      137 primary gastric carcinomas. In the non-neoplastic mucosa, STN was expressed
      in all goblet cells, most absorptive cells and Paneth cells of intestinalized
      tubules, whereas it was not seen in the gastric mucosa proper. We evaluated the
      association between the mucin-histochemical findings of intramucosal carcinomas
      and the STN-expression. STN was expressed in 8 of 20 undifferentiated-type
      carcinomas, all of which were mucin-histochemically of the gastric type. STN was
      expressed in 25 of 51 differentiated-type carcinomas, among which it was
      expressed in 3 of 12 gastric-type, 11 of 17 intestinal-type and 11 of 22 mixed
      type adenocarcinomas. The extent of STN expression in the intestinal-type
      adenocarcinomas was significantly higher than in gastric-type adenocarcinomas and
      undifferentiated-type carcinomas, and that seen in mixed-type adenocarcinomas was
      significantly higher than in the gastric-type adenocarcinomas. We also examined
      STN expression in early and advanced carcinomas. As the depth of carcinoma
      invasion progressed, the extent of STN expression was significantly higher and
      its incidence was significantly higher. Our findings suggest that STN expression
      reflects intestinalization of the gastric mucosa, and that a kind of intestinal
      metaplasia occurs in progressing gastric carcinoma cells.

PMID- 8253527
TI  - Hodgkin's disease: the protective effect of childbearing.
AB  - Register and census data for complete cohorts of Norwegian men and women born
      between 1935 and 1974 were used to examine the relationship between reproductive
      factors and the incidence of Hodgkin's disease (HD). Among 1.3 million men and
      1.3 million women under observation, 695 male and 441 female cases of HD were
      diagnosed during the period of follow-up. Our hazard model estimates showed that
      women, at a given age and in a given birth cohort, have an HD incidence inversely
      related to current parity. A clear relationship was found only for the nodular
      sclerosis subtype. In men, the risk of HD development was higher than that in
      childless women, and there was no parity effect. The lower HD incidence among
      high-parity women could not be ascribed to their lower social status. Presumably,
      there is a still unidentified protective factor associated with the biology of
      childbearing, the effect of which possibly wears off with increasing length of
      time since childbirth. In addition, there are indications of a net effect of age
      at entry into motherhood, which may explain part of the estimated parity effect.

PMID- 8253528
TI  - Low incidence of c-Ha-ras gene mutations in benign and malignant cutaneous
      lesions from transplant recipients.
AB  - Transplant recipients successively develop benign, premalignant and malignant
      skin lesions on sun-exposed areas. It has been suggested that UV radiations might
      induce mutations in ras oncogenes and p53 tumour-suppressor gene, responsible for
      skin cancers. With PCR and oligoprobe hybridization, we investigated c-Ha-ras
      gene mutations at codons 12 and 61 in 120 cutaneous lesions from grafted
      patients, since they could represent a marker of the evolution of benign skin
      lesions towards malignancy in this population; 29 similar skin biopsies from non
      immunosuppressed patients were also analyzed. In transplant recipients, we
      detected mutations at codon 12 only in 1/42 non-melanoma skin cancers and 2/29
      pre-cancerous keratoses. No mutation was detected in 11 cases of cutaneous
      Bowen's disease from grafted patients and in pre-malignant and malignant skin
      samples from control patients. Benign warts exhibited an overall incidence of 18%
      and 15% of mutations at codon 12 of c-Ha-ras gene in grafted and control patients
      respectively. We detected only one mutation at codon 61 in a plantar wart. Human
      papillomaviruses (HPV) are thought to be involved in the malignant evolution of
      cutaneous disorders in transplant recipients and cooperate with a ras oncogene to
      induce malignancy in vitro. The presence of HPV DNA in our series of skin samples
      from grafted patients showed no correlation with the occurrence of c-Ha-ras
      mutations. Our findings indicate that c-Ha-ras-gene activation by mutations is
      rare in cutaneous lesions from transplant recipients, and is unlikely to play a
      crucial role in transformation towards malignancy in skin carcinogenesis among
      grafted patients.

PMID- 8253529
TI  - Normal breast epithelial cells produce interleukins 6 and 8 together with tumor
      necrosis factor: defective IL6 expression in mammary carcinoma.
AB  - Virtually pure primary cultures of normal mammary epithelial cells (MEC) obtained
      from healthy women were shown to release interleukin 6 and 8 (IL6, IL8) and to
      produce a nonsecreted form of tumor-necrosis factor (TNF). No interferon (IFN),
      whether alpha, beta, or gamma, or IL1-alpha or -beta could be detected. Analysis
      of cellular RNA confirmed these findings and showed that MEC also express IL6
      receptor and TNF-alpha-related mRNAs. Epithelial cells were selectively stained
      by antibodies to IL6, IL8 and TNF-alpha both in primary cultures and in the
      normal mammary gland. Samples of human milk contained sizable amounts of IL6, IL8
      and IFN-gamma; yet the liquid phase was consistently negative for other cytokines
      (i.e., TNF-alpha, IFN-alpha/-beta, IL1-alpha/-beta). Expression of IL6 (but not
      of IL8 and TNF-alpha) was abolished in ductal infiltrating carcinomas and greatly
      reduced in cultures of oncogene-transfected mammary cells, suggesting that
      alterations of IL6 expression are associated with pathogenesis in breast cancer.

PMID- 8253530
TI  - Targeting of T lymphocytes against EGF-receptor+ tumor cells by bispecific
      monoclonal antibodies: requirement of CD3 molecule cross-linking for T-cell
      activation.
AB  - Targeting of T lymphocytes against epidermal growth-factor-receptor (EGF-R)+
      tumor cells was achieved by constructing a hybrid hybridoma which secretes an
      anti-EGF-R/anti-CD3 bispecific monoclonal antibody (biMAb) of hybrid isotype
      (IgG1/IgG2a). Purification of biMAb molecules from parental anti-EGF-R and anti
      CD3 MAbs was performed by protein-A chromatography. The purified biMAb was able
      to trigger the lysis of EGF-R+ tumor cell lines (A431, IGROV-1, MDA-468 and U-87)
      and of NIH-3T3 transfectants expressing human EGF-R by cytolytic T lymphocytes,
      but it was ineffective in the case of EGF-R-negative tumor targets. Normal EGF-R+
      cells (keratinocytes and endometrial cells) were also susceptible to biMAb
      targeted cytolysis. However, the amount of biMAb required to induce half-maximal
      cytolysis of tumor cells over-expressing the EGF-R molecule (A431) was
      considerably lower than that required to induce lysis of EGF-R+ tumor or normal
      cells which express EGF-R at considerably lower density. The ability of such
      biMAbs to deliver activation signals to T cells was evaluated by Ca++
      mobilization and lymphokine production experiments. The soluble anti-EGF-R/anti
      CD3 biMAb failed to induce intracellular Ca++ increases, which occurred only
      after cross-linking induced by an anti-mouse IgG antibody. Secretion of
      lymphokines (IFN-gamma, TNF-alpha and GM-CSF) was induced by contact of the biMAb
      coated effector cells with the relevant tumor target, whereas the soluble biMAb
      was virtually ineffective. In addition, biMAb-coated effector cells retained the
      ability to recognize and to lyse EGF-R+ tumor cells for a prolonged period of
      time. Our data indicate that activation of effector cells targeted by biMAbs can
      only occur at the tumor site, where cross-linking of surface CD3 molecules is
      induced by contact with the tumor cells.

PMID- 8253531
TI  - Specificity and properties of MAb RS7-3G11 and the antigen defined by this
      pancarcinoma monoclonal antibody.
AB  - The murine monoclonal antibody (MAb) RS7-3G11 is an IgG1 with pancarcinoma
      reactivity, which has been raised against human squamous-cell carcinoma of the
      lung. Immunoperoxidase staining of frozen tissue sections demonstrated that the
      antigen defined by RS7-3G11 is present in tumors of the lung, stomach, bladder,
      breast, ovary, uterus and prostate. The rate and extent of internalization of RS7
      3G11 into Calu-3, an adenocarcinoma of the lung cell line, was investigated using
      unconjugated MAb, followed by fluorescence labelling, and by binding 125I-RS7
      3G11 followed by acid removal of surface-bound antibody. Rapid internalization of
      MAb RS7-3G11 into target cells was observed. Antibody internalization was noted
      at 30 min, and by 2 hr virtually all MAb RS7-3G11 was internal. Although MAb RS7
      3G11 was raised against non-small-cell carcinoma of the lung, ME-180, a cervical
      carcinoma cell line, expresses higher quantities of the antigen than the lung
      carcinoma cell lines. Due to the higher antigen density in ME-180 cells, this
      line was used for immunoprecipitation studies and antigen purification.
      Immunoprecipitation studies using the ME-180 cervical-carcinoma cell line
      metabolically labeled with [3H]leucine or [3H]glucosamine demonstrated that the
      antigen defined by RS7-3G11 is a glycoprotein of M(r) 46 kDa. Deglycosylation by
      treatment with endoglycosidase-F resulted in a protein with a M(r) of 35 kDa. RS7
      3G11-antigen was purified from ME-180 tissue-culture cells using affinity-column
      chromatography. By SDS-PAGE it was seen that the antigen was highly purified. The
      major band appeared at M(r) of 45 to 48 kDa. This result is in agreement with the
      immunoprecipitation studies. The broad band observed in the SDS-PAGE is typical
      of many glycoproteins, and suggests heterogeneity of glycosylation. Chemical and
      enzymatic treatments of the antigen, followed by Western blot analyses, suggest
      that the RS7-3G11 antigenic determinant is composed of a conformation-dependent
      peptide.

PMID- 8253533
TI  - Effect of serum and cell density on transmembrane distribution of cAMP and cGMP
      in transformed (C4-I) and non-transformed (WI-38) human cells.
AB  - The ratio between cGMP and cAMP in plasma/urine is elevated in several types of
      malignancies. The present in vitro study showed that the ratio between
      extracellular cGMP and cAMP increased during the proliferation of C4-I cells
      (derived from a carcinoma of the uterine cervix), whereas this ratio decreased in
      WI-38 cells (normal lung fibroblasts). These results can be explained by
      differences between the transformed and non-transformed cells in the cell-density
      dependent transmembrane distribution and intracellular levels of cyclic
      nucleotides. In the serum-deprived cultures, no profound effects were seen on the
      cell-density-dependent biokinetics of cAMP and cGMP. In the absence of serum,
      growth of C4-I cells was markedly retarded, whereas WI-38 cells were unable to
      expand at all.

PMID- 8253532
TI  - Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein
      tyrosine phosphatase homologous to cytoskeletal-associated proteins.
AB  - We have investigated the mRNA expression of 2 human protein tyrosine phosphatases
      with sequence homology to cytoskeletal proteins, PTPH1 and PTPMEG. Northern-blot
      analysis of PTPH1 using poly (A)+ RNA from normal human colon tissue showed a low
      abundance message of 4.3 kb. Reverse-transcriptase/polymerase-chain reaction (RT
      PCR) was therefore used to detect it in a wide variety of cell lines including 9
      colorectal, 5 gastric, 5 hepatic and 6 hematopoietic tumor cells. PTPH1 mRNA was
      not detected only in Colo 320 cells over-expressing c-myc mRNA, among the
      colorectal cancer cell lines examined. When Colo 320 cells were incubated with 5
      mM sodium butyrate for 5 days, PTPH1 mRNA became detectable, concomitant with the
      marked decrease in the expression level of c-myc mRNA. Moreover, the chromosomal
      localization of PTPH1 gene was investigated by fluorescence in situ
      hybridization. Interestingly, PTPH1 gene was mapped to 9q31 where the gene for
      Gorlin syndrome, a putative tumor suppressor gene, exists.

PMID- 8253534
TI  - Effect of epidermal growth factor and transforming growth factor beta 1 on growth
      and invasive potentials of newly established rat bladder carcinoma cell lines.
AB  - We established 5 rat bladder cell lines (MYU3L, MYU4, MYU6s, MYKU1L and MYP3).
      EGF stimulated DNA synthesis of all the cells in monolayer culture, regardless of
      the number of EGF receptors. In soft agar, only MYU3L formed colonies, and EGF
      enhanced their growth. However, EGF did not induce the other cells to grow in
      soft agar. In contrast, TGF-beta 1 inhibited the growth of the cells, but a
      tumorigenic cell and the cells which were established from large in vivo tumors
      were more resistant than the others to TGF-beta 1. We tested the effect of growth
      factors on the invasive potential of MYP3 cells (non-tumorigenic), MYU3L cells
      (tumorigenic/highly invasive but not metastatic) from newly established cell
      lines, and another metastatic cell line, LMC19. MYP3 expressed only a trace
      amount of 92-kDa gelatinase (MMP-9), whereas MYU3L expressed interstitial
      collagenase (MMP-1) and MMP-9, and LMC19 expressed 72-kDa gelatinase (MMP-2) and
      MMP-9. The release of MMP-2 in LMC19 was stimulated by TGF-beta 1, but EGF had no
      effect on the release of any MMPs in either type of cells. These observations
      suggest that EGF acted as a mitogen on all the cells tested, but did not enhance
      the malignant phenotype. Further, the loss of responsiveness to the suppressive
      effect of TGF-beta 1 may be an important step toward a malignant phenotype. Some
      of malignant tumors may utilize TGF-beta 1 for enhancing their invasive and
      metastatic potential.

PMID- 8253535
TI  - TPA-enhanced invasion of Matrigel associated with augmentation of cell motility
      but not metalloproteinase activity in a highly metastatic variant (L-10) of human
      rectal adenocarcinoma cell line RCM-1.
AB  - We previously found that the enhanced activity to invade Matrigel upon
      stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA) was one of the major
      properties of a highly metastatic variant (L-10) of a human rectal adenocarcinoma
      cell line RCM-1. To clarify the mechanism of this enhancement, we examined the
      effect of TPA on 2 major biological factors involved in tumor cell invasion: cell
      motility and matrix-degrading metalloproteinase activity. The enhanced
      invasiveness was inhibited by protein-kinase-C inhibitors. TPA markedly enhanced
      both haptotactic response to type-IV collagen and motility on tissue-culture
      glass substrate of L-10 cells in a dose-response manner quite similar to that of
      TPA-enhanced invasion of Matrigel. On the other hand, TPA showed little
      enhancement of metalloproteinase production, which was assessed by gelatin- and
      casein-zymography, and of type-IV collagenolytic activity. Addition of TIMP
      (tissue inhibitors of metalloproteinase)-I inhibited TPA-enhanced invasion of
      Matrigel by only up to 13%. Thus, TPA treatment of L-10 cells enhanced invasion
      of Matrigel in association with augmentation of cell motility but did not enhance
      metalloproteinase activity.

PMID- 8253536
TI  - p53 protein accumulation and gene mutations in human glioma cell lines.
AB  - Mutations in, and aberrant expression of, the p53 tumor suppressor gene were
      assessed in 17 cell lines derived from human malignant brain tumors (glioblastoma
      multiforme). Exons 5 through 8 were screened by single strand conformational
      polymorphism analysis (SSCP), followed by direct DNA sequencing. Mutations were
      found in 6 of 17 glioma cell lines, i.e., at a frequency similar to that found in
      primary malignant gliomas. Loss of the wild type allele was observed in 4 of the
      mutated cell lines. Two cell lines had the same mutation (CGG-->TGG; Arg-->Trp)
      in codon 248. Five of 6 mutations were transitions, 4 of which occurred at CpG
      dinucleotides. In one cell line a 10-bp deletion at the intron 4/exon 5 junction
      was found. Five of 6 glioma cell lines contained a mutation identical to that in
      the respective primary tumor despite prolonged in vitro culture (140-221
      passages). Thus, the acquisition of p53 mutations during culture appears to be
      infrequent. Two cell lines derived from heterozygous tumors maintained the wild
      type p53 allele during long term culture. p53 protein levels were assessed by
      immunofluorescence cytochemistry and immunoprecipitation followed by Western blot
      analysis and revealed elevated levels of the p53 protein, although to a variable
      extent, in all cell lines with p53 mutations. A marked p53 protein accumulation
      was also observed in two cell lines lacking p53 mutations in exons 5 through 8,
      indicating that a prolonged half life of the gene product is not solely dependent
      on an aberrant coding sequence. The remaining cell lines had either low levels or
      no detectable p53 protein; one of the latter contained a gross rearrangement of
      the p53 gene. Our results suggest that with respect to p53 gene status, glioma
      cell lines usually resemble the original tumors and may, therefore, be suitable
      for studying the biological changes associated with p53 mutations in glial
      tumors.

PMID- 8253537
TI  - Allogeneic blood transfusion reduces murine pulmonary natural killer (NK)
      activity and enhances lung metastasis of a syngeneic tumour.
AB  - A model was established whereby C57BL/6 (B6) blood injected i.v. into C3H mice 7
      days prior to i.v. injection of syngeneic UV-2237 tumour cells significantly
      increased the number of pulmonary metastases counted 21 days later as compared
      with levels observed in mice treated with saline, C3H or NZW blood or SRBC. This
      regimen of B6 allogeneic blood transfusion of C3H mice also significantly
      depressed splenic and pulmonary NK activity as assayed by lysis of 51Cr YAC-I in
      vitro and by clearance of 111In YAC-I in vivo respectively. Anti-asialo GMI
      treatment, which depletes NK activity in vivo, and Poly I:C treatment, which
      enhances NK activity in vivo, were associated with significantly increased and
      decreased pulmonary metastasis of UV-2237, respectively, in C3H mice. Depletion
      of CD4+ and CD8+ T cells had no effect. Cyclophosphamide pretreatment which,
      among other effects, depletes NK cells, significantly increased pulmonary
      metastasis of UV-2237 in C3H mice. This was corrected by adoptive transfer of
      normal C3H spleen cells but not spleen cells from anti-asialo GMI-treated C3H
      mice or B6-blood-transfused C3H mice. Furthermore, a 1:1 mixture of normal C3H
      spleen cells with spleen cells from B6-blood-transfused C3H mice also failed to
      reconstitute the cyclophosphamide-pre-treated C3H mice. We conclude that
      allogeneic blood transfusion augments pulmonary metastasis of the UV-2237 sarcoma
      in C3H mice and that the mechanism involves suppression of NK activity.

PMID- 8253538
TI  - Effect of synthetic thymic hormones on the cocaine-induced inhibition of the
      primary immune response in mice.
AB  - The effects of thymosin alpha 1 (T alpha 1) and thymopentin (TP5) on the cocaine
      induced impairment of the primary antibody response to sheep red blood cells
      (SRBC) was studied. The administration of cocaine from day -4 to the day of
      immunization (day 0) induced a significant impairment of the response to the T
      dependent antigen SRBC, as evaluated on day 5 post-immunization by the Splenocyte
      Induced SRBC Hemolysis (SIH) assay. The analysis of the responses to immunogen
      elicited from each single mouse indicated that, under the experimental conditions
      used, cocaine acted by exerting more an "all or nothing" effect rather than by
      modulating the strength of the immune response. Both T alpha 1 and TP5, injected
      into mice during cocaine administration and for 4 days after, induced a
      significant recovery of the response to SRBC. Our experiments did not show any
      great differences in the overall efficacy of the two drugs, although they showed
      quite a different dose-response effect. The results of the present investigation
      demonstrated the capability of TP5 and T alpha 1 to reverse the cocaine-induced
      impairment of the response to SRBC and suggested that the effect of the two
      peptides may be related to their immunomodulating activities on T-cell functions.

PMID- 8253539
TI  - Study of procainamide hapten-specific antibodies in rabbits and humans.
AB  - Procainamide (PA) is the drug most commonly associated with the induction of
      autoantibodies and drug-related lupus (DRL). While the majority of these patients
      express autoantibodies, antibodies to the parent drug and metabolites, PA
      hydroxylamine (PAHA) or nitroso-PA (NOPA), have not been reported in humans.
      Hapten-carrier conjugates were prepared using human hemoglobin (HgB) or
      autologous rabbit erythrocytes with PAHA or NOPA. PA was conjugated to rabbit
      serum albumin (RSA) or egg albumin (OVA) via diazotization and condensation
      methods. Rabbits were immunized with hapten conjugates in Freund's adjuvant.
      These hapten-carrier compounds (5-10 micrograms/ml) were used as test antigens
      for antibodies in sera from the rabbits and 40 patients on chronic PA treatment.
      10 SLE patients, 33 elderly and 20 young normal controls by ELISA. Type I and II
      collagens were also used as test antigens for human sera. Sera from rabbits
      immunized with the PA compounds had elevated IgG antibody values to PA, PAHA and
      NOPA, but no autoantibodies. Absorption of the rabbit sera with the PA compounds
      reduced the antibody levels; ssDNA and histones failed to inhibit the total
      binding values. Mean binding to PA-OVA was 0.95 +/- 0.41 for PA patients and 1.37
      +/- 0.26 standard error of means (S.E.M.) in the SLE patients compared to 0.37 +/
      0.14 S.E.M. in the normal sera (P < or = 0.05); similar binding values to PAHA
      HgB and NOPA-HgB were also observed. Sixty-eight percent of the PA patients had
      antibodies to type II collagen. Elevated binding values to PA compounds were
      inhibited by absorption of human sera with ssDNA or total histones; absorption
      with PA or PAHA had no significant effect. These findings suggest that sera from
      PA patients containing high titers of autoantibodies cross-react in vitro with
      unrelated antigens.

PMID- 8253540
TI  - Spleen and thymus cell subsets modified by long-term morphine administration in
      protein-undernourished mice--I.
AB  - Severe infections in intravenous drug abusers could be the consequence of
      morphine-induced damage on the immune system. To evaluate the long-term effect of
      in vivo morphine administration on the immune system we developed an experimental
      model where we studied the combined effects of morphine treatment and protein
      malnutrition. We treated protein-undernourished mice daily for 11 weeks with
      increasing doses of morphine. Morphine treatment produced a decrease in body
      weight and spleen cell number. The changes observed were partially independent of
      the nutritional status of the host. Saline-injected mice showed a decrease in the
      percentage of Thy 1+ cells in the spleen. Morphine treatment induced a decrease
      in the total number of cells and therefore in the absolute number of T-(Thy 1,
      CD4, CD8), B- and Mac 1+ (macrophages) cells in protein-undernourished mice.
      Saline-injected mice showed a decrease in the percentage of Thy 1+ cells and an
      increase in the percentage of B- and Ia(+)-cells in the spleen. We conclude that
      morphine altered the immune system by down-regulating splenocyte proliferation.
      We also studied the effects of i.p. administered morphine on expression of
      thymocyte phenotype in well-nourished and protein-undernourished mice. In well
      nourished mice, morphine treatment reduced the number of Thy 1+, CD4+ and CD8+
      cells per thymus to 30% of that found in untreated mice and to 40% of the cells
      in those saline-treated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253541
TI  - Spleen and thymus cell subsets modified by long-term morphine administration and
      murine AIDS--II.
AB  - Intravenous heroin abusers suffer a great variety of infections, including AIDS
      (acquired immune deficiency syndrome). We developed an experimental mouse model
      to evaluate the long-term effect of in vivo morphine administration during
      retrovirus-induced immune dysfunction. Mice were treated daily for 11 weeks with
      increasing doses of morphine. Morphine treatment produced a decrease in body
      weight and spleen cell number. Murine retrovirus infection provoked an increase
      in body weight due to enlargement of lymphoid organs, and an increase in the
      percentage and absolute number of CD4+ and Mac 1+ cells. Interestingly,
      retrovirus-infected mice that were also morphine-treated did not show the
      increase in the relative proportion of Mac 1+ cells. Moreover, under the
      experimental conditions of protein-malnutrition and morphine treatment
      potentiation of immune dysfunction by murine retrovirus infection was
      investigated. Retrovirus infection-induced splenocyte proliferation was partially
      regulated by morphine treatment. Splenocytes from retrovirus-infected mice
      presented a higher percentage of IL-2R+ cells and, lower levels of sIL-2R in
      splenocyte supernatants. Mitogen-stimulated splenocytes had a lower production of
      interferon-gamma as well as an increase in the secretion of tumor necrosis factor
      alpha. Thus morphine altered the immune system by down-regulating splenocyte
      proliferation, because retrovirus infection-induced splenocyte proliferation was
      partially regulated by morphine treatment. We also evaluated the effects of joint
      murine retrovirus infection and protein undernutrition on the thymus cell
      subsets. Retrovirus infection was associated with a decrease in the absolute
      number of Thy 1+, CD4+ and CD8+ cells per thymus with the CD8+ cell subset being
      the most affected. Moreover, retrovirus-infected mice presented a dramatic
      decrease in the percentage of double-positive (CD4+ CD8+) cells in the thymus as
      well as changes in its immunoarchitecture. While protein undernutrition alone did
      not produce further differences between infected versus non-infected, protein
      undernourished, morphine treatment induced a greater decrease in thymocyte number
      than that seen in retrovirus- or morphine-treated animals alone.

PMID- 8253542
TI  - A characterization of the in vivo immunomodulation by Met-enkephalin in mice.
AB  - Single intraperitoneal injections of Met-enkephalin (MENK) into CBA mice
      decreased the phagocytic activity of peritoneal macrophages, Con-A-induced
      proliferation and NK-activity of spleen cells. Conversely, in mice which had been
      immunized with sheep erythrocytes, treatment with MENK was associated with
      enhancement of phagocytosis, and no effect on lymphoid proliferation and NK
      cytotoxicity of spleen cells. MENK-induced inhibition of cellular functions in
      nonimmunized mice was associated with a decrease of plasma ACTH level, whereas
      MENK-induced stimulation of phagocytosis in immunized mice was paralleled with an
      elevation of ACTH, suggesting a role of corticoids in immunomodulation by MENK.
      MENK-induced modulation (suppression and stimulation) of phagocytosis, as well as
      inhibition of spleen cell proliferation, was not observable in adrenalectomized
      mice, although a reduced NK-cytotoxicity was still present.

PMID- 8253543
TI  - Specificity of estrogen receptors in rat thymus.
AB  - Estrogens exert their effects in reproductive tissues through a primary binding
      reaction with specific receptor proteins which can be detected and characterized
      in high speed cytosols. Administered estrogens have profound atrophic effects on
      the developing thymus and alter thymocyte responsiveness to mitogens in vitro.
      Estrogen-binding macromolecules have been described in rat thymus cytosol, and an
      attempt has been made to characterize thoroughly the ligand specificity of these
      moieties, and compare this with the specificity of the uterus estrogen receptor.
      Cytosols were prepared from immature rat thymus and uterus and incubated with
      [3H]estradiol alone or with one of a range of unlabeled steroids: estradiol-17
      alpha (E2-17 alpha), estradiol-17-beta (E2-17 beta), diethylstilbestrol (DES),
      estriol (E3), estrone (E1), corticosterone (C), testosterone (T) or progesterone
      (P). Scatchard plots were derived from the binding isotherms obtained and the
      molar dissociation constant (Kdi) for each inhibitor measured. In both thymus and
      uterus, binding of [3H]estradiol was inhibited most potently by substances
      possessing estrogen agonist activity, and the rankings of potencies in both
      tissues were broadly similar, namely: DES > E2-17 beta (thymus); DES = E2-17 beta
      (uterus). In both tissues, E2-17 beta > E2-17 alpha and E3 > E1 > C > T > P.
      There were significant differences between thymus and uterus, in that the
      estrogen receptor in the former tissue exhibited a significantly higher
      selectivity for some estrogens, including DES and for corticosterone. These
      differences may underlie differential responsiveness of the two tissues to
      steroids, and may reflect structural differences between thymus and uterus
      estrogen receptors.

PMID- 8253544
TI  - Kidney dysfunction in the arthritic rat.
AB  - Kidney function and histopathology were investigated in the adjuvant-induced
      arthritic rat. Rats injected with Mycobacterium butyricum exhibited symptoms of
      arthritis (i.e. paw edema and loss of body weight) by day 9 which worsened and
      included systemic manifestations of the disease on days 16 and 30. Definite signs
      of kidney dysfunction were observed by day 16 which included elevated urine
      output and plasma creatinine values and decreased creatinine clearance. By day
      30, these parameters were similar to the values obtained from normal rats;
      however, kidney weights from arthritic rats than those from normal rats.
      Histopathologic abnormalities observed in the kidneys of arthritic rats on day 30
      included tubular lesions consisting of focal basophilia, edema, granular deposits
      and basement membrane thickening. Changes in the glomerulus included granular
      deposits with focal glomerulopathy. These findings are the first to clearly
      demonstrate kidney dysfunction and histopathologic alterations associated with
      the early expression of the adjuvant-induced disease process in the rat. Our
      observations in the rat suggest that renal dysfunction in man can be mediated by
      the inflammatory disease process and is not solely a drug treatment-induced side
      effect.

PMID- 8253545
TI  - Primary extrauterine endometrial stromal neoplasms: a clinicopathologic study of
      20 cases and a review of the literature.
AB  - We present the results of a clinicopathologic study of 20 patients with primary
      extrauterine endometrial stromal sarcoma (ESS). The sites of the primary neoplasm
      and the number of patients with sufficient follow-up for survival analysis are as
      follows: ovary (three of four), fallopian tube (one of one), pelvic cavity (six
      of eight), abdominal cavity (five of six), and retroperitoneum (one of one).
      Evaluation of all patients included the mitotic index (MI) and cytologic atypia.
      Thirteen of the sixteen patients eligible for survival analysis had tumors with
      an MI < 10 and would be classified as low-grade stromal sarcomas in the Norris
      and Taylor scheme. Eight (62%) of the 13 had one or more relapses; of these,
      three died of disease at 35, 108, and 120 months, respectively, and another
      patient was alive with disease at 96 months. The other four patients who were
      treated after a relapse showed no evidence of disease after relapse at 36, 57,
      63, and 146 months, respectively. Two of the 13 patients had tumor considered
      unresectable at the time of diagnosis; both died of disease at 5 and 10 months,
      respectively. Neither MI nor cytologic atypia were predictive of tumor recurrence
      or death from tumor. We also extracted clinical and morphologic data from all
      previous reports of primary extrauterine ESS, combined them with our 20 patients,
      and then compared the combined group with 17 cases of primary high-stage uterine
      ESS we presented in an earlier report. Not surprisingly, the behavior of the
      primary extrauterine ESS was more reminiscent of high-stage primary uterine ESS
      than low-stage primary uterine ESS.

PMID- 8253546
TI  - Association of endometrial epithelial metaplasias with endometrial carcinoma and
      hyperplasia in Japanese and American women.
AB  - We reviewed endometrial tissue from 166 cases of endometrial adenocarcinoma and
      hyperplasia--91 seen at Kyushu University, Fukuoka, Japan, and 75 at George
      Washington University, Washington, D.C., U.S.A.--to compare the prevalence of
      epithelial metaplastic changes in the two populations. Metaplasias were more
      common in the benign endometrium associated with carcinoma at George Washington
      University (78%) than at Kyushu University (54%). They were associated with
      carcinomas of lower grade and accompanied by hyperplasia at both institutions.
      These results indicate that endometrial metaplasias, like endometrial
      hyperplasias, tend to be associated with less virulent endometrial carcinomas and
      to be more common in American women (who represent a high-risk population for
      endometrial carcinoma) than in Japanese women (in whom the risk is low but
      rising.

PMID- 8253547
TI  - Flow cytometry and AgNORs in benign, borderline, and malignant mucinous and
      serous tumours of the ovary.
AB  - We performed flow cytometry and AgNOR counts on 117 serous and mucinous ovarian
      tumours, comprising 56 cystadenomas, 21 borderline tumours, and 40
      cystadenocarcinomas. DNA aneuploidy was present in one cystadenoma and in 11% of
      mucinous and 46% of serous cystadenocarcinomas. All borderline tumours were DNA
      diploid. Major and minor FIGO stages and flow cytometrically determined DNA
      ploidy and DNA index were prognostically significant. Age, histological type
      (serous versus mucinous), flow cytometric proliferative index, and AgNOR counts
      were not predictive of survival. Cystadenomas and borderline tumours had lower
      rates of proliferation than cystadenocarcinomas. AgNORs correlated with DNA
      ploidy and proliferative index. Borderline tumours showed elevated AgNOR numbers
      despite low proliferative indices and universal DNA diploidy, suggesting that
      AgNOR numbers may be related to nuclear events other than proliferation and DNA
      ploidy.

PMID- 8253548
TI  - Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year
      retrospective clinicopathological and DNA flow cytometric analysis.
AB  - This retrospective study reports the incidence of hydatidiform mole in a
      population of 19,457 pregnancies over a 3-year period. During the study period
      all "products of conception" from first and second trimester abortions were
      referred for pathological examination. Coded histologic sections were reviewed
      using the published histologic criteria for hydatidiform mole. Ploidy was
      estimated by DNA flow cytometry. Clinical data were retrieved from maternal case
      notes. Thirty-eight cases were confirmed as hydatidiform mole, 10 (26%) as
      complete mole, and 28 (74%) as partial mole. Twenty-three cases of partial mole
      (88%) were triploid, and nine of 10 complete moles were diploid. The incidence of
      hydatidiform mole was 1:512 pregnancies, (complete mole, 1:1,945; partial mole,
      1:695). Only one case (3.5%) of partial mole was suspected clinically. One case
      of persistent gestational trophoblastic disease occurred following a complete
      mole. No sequelae were encountered following partial mole. We conclude that
      hydatidiform mole is a common condition and the majority of cases are partial
      moles. Quantitatively imprecise morphologic criteria contribute to the inaccuracy
      in reporting of partial mole; analysis of ploidy is useful in the evaluation of
      problem cases. Follow-up of partial mole is warranted because its true biological
      potential is as yet unclear.

PMID- 8253549
TI  - Multiple nodules of intermediate trophoblast following hydatidiform moles.
AB  - After removal of a complete hydatidiform mole, seven patients developed an
      unusual complication characterized by a proliferation of intermediate trophoblast
      forming nodules in the endometrium or myometrium. The patients were examined
      because of vaginal bleeding or mildly elevated human chorionic gonadotrophin
      (HCG) titers. Three patients were cured by hysterectomy, one by endometrial
      curettage, one by endometrial curettage plus chemotherapy, and one (who also had
      choriocarcinoma) by multiple doses of chemotherapy after hysterectomy; the
      seventh patient was lost to follow-up. These nodules probably represent a mild
      form of postmolar trophoblastic disease.

PMID- 8253550
TI  - Proliferative and histologically malignant struma ovarii: a clinicopathologic
      study of 54 cases.
AB  - We reviewed 54 cases of struma ovarii with histologic features diverging from the
      normal pattern of benign thyroid tissue. These 54 lesions were divided into
      proliferative struma (41 cases) and malignant struma (13 cases). The patients
      diagnosed with proliferative struma ovarii ranged in age from 18 to 84 years
      (average, 44 years). The most common clinical findings among the proliferative
      struma patients were a mass (58%) and acute abdominal pain (12%). Preoperative
      evidence of hyperthyroidism was noted in three of the patients with proliferative
      struma, whereas one additional patient presented with ascites and hydrothorax
      ("pseudo-Meigs' syndrome"). Proliferative struma differed from the usual struma
      ovarii in that they comprised areas of densely packed follicles or papillary
      formations that raised the possibility of malignancy. However, none of the
      lesions that we have designated as proliferative struma ovarii showed histologic
      evidence of overlapping "ground glass" nuclei, vascular space invasion, or
      mitotic activity that would have supported an unequivocal diagnosis of
      malignancy. None developed metastases or recurrent disease. The 14 malignant
      struma ovarii manifested the classical features of thyroid carcinoma (including
      the presence of overlapping "ground glass" nuclei lining papillary formations and
      vascular space invasion). Patients with malignant struma ovarii ranged in age
      from 30 to 77 years (average, 50 years). Their clinical presentations included a
      mass (78%) and acute abdominal pain (22%). One patient had clinical and
      laboratory evidence of hyperthyroidism. On follow-up, one patient had persistent
      disease with peritoneal involvement, but distant metastases did not develop in
      any of these patients. A diagnosis of malignant struma ovarii should be reserved
      for lesions that exhibit the full range of changes seen in thyroid carcinoma
      arising in the cervical thyroid. By requiring that these rigid criteria be
      adhered to, the diagnosis of malignant struma ovarii will probably become less
      frequent as the more commonly encountered proliferative struma ovarii are
      recognized.

PMID- 8253551
TI  - Vulvar vestibulitis is rarely associated with human papillomavirus infection
      types 6, 11, 16, or 18.
AB  - Vulvar vestibular biopsy specimens from 31 women with clinical and pathologic
      findings of vulvar vestibulitis were studied using polymerase chain reaction
      (PCR) for the identification of human papilloma virus (HPV). The PCR technique
      specifically probed for HPV types 6, 11, 16, and 18. Of the 31 subjects, three
      were found to have HPV within the biopsy specimens; two had HPV type 11 and one
      had HPV 16. Five of the 31 cases had histopathologic features of koilocytosis
      consistent with HPV effect; three of these five were found to have HPV. The
      findings support the hypothesis that HPV types 6, 11, 16, and 18 are rarely
      associated with vulvar vestibulitis. The frequencies identified were similar to
      those seen with control patients. True koilocytosis is the most useful pathologic
      feature distinguishing HPV-related cases; it is rarely identified in typical
      vulvar vestibulitis. Nonspecific changes in the vestibular epithelium associated
      with glycogen effect should not be interpreted as koilocytosis.

PMID- 8253552
TI  - Bilateral ovarian cysts with squamous intraepithelial neoplasia.
AB  - We report a case of bilateral ovarian cysts lined exclusively by squamous
      epithelium showing multifocal intraepithelial neoplasia. The cervix showed
      synchronous high-grade intraepithelial neoplasia (CIN III). We interpreted the
      ovarian lesions as squamous carcinoma of borderline malignancy and believe that
      they are part of a "field change" that also involves the cervix.

PMID- 8253553
TI  - Accidental detection of nonmetastatic ovarian adenocarcinoma in tissue samples
      recovered during dilatation and curettage.
AB  - We report two patients with ovarian cancer who were diagnosed with primary
      endometrial cancer when detached fragments of adenocarcinoma were identified in
      their dilatation and curettage specimens. Retrospectively, a fragment of
      fallopian tube and ovarian stroma were identified in the specimens. These
      findings served to alert the pathologist to the possibility that extrauterine
      sampling had occurred as a result of perforation of uterine wall during
      dilatation and curettage. Previous studies have focused on the cytologic
      detection of extrauterine cancer or on cases where metastasis to the endometrium
      has led to a misdiagnosis of primary endometrial cancer.

PMID- 8253554
TI  - Eosinophilic perifolliculitis: a variant of autoimmune oophoritis?
AB  - We report two middle-aged women with ovarian perifolliculitis consisting mostly
      of eosinophils. Both had enlarged cystic ovaries that on histological examination
      showed a perifollicular inflammatory infiltrate consisting of lymphocytes, plasma
      cells, and large numbers of eosinophils. The inflammatory infiltrate increased in
      intensity with follicular maturation and appeared to be destroying the theca
      interna. Circulating antiovarian, antiadrenal, and antithyroid antibodies were
      negative in both cases. We also compare these cases to lymphoplasmacytic
      autoimmune oophoritis.

PMID- 8253555
TI  - Assessment of quality of life in head and neck cancer patients.
AB  - Seventy-five consecutive patients were selected to evaluate a disease-specific
      quality-of-life questionnaire (UW QOL). The new test was compared to two
      established equality of life evaluation tools, the Karnofsky scale and the
      Sickness Impact Profile (SIP). Each test was administered on three separate
      occasions: (1) several days preoperatively; (2) immediately postoperatively; and
      (3) 3 months postoperatively. The Karnofsky scale is relatively crude and lacks
      the ability to measure subtle changes. The SIP is a detailed questionnaire that
      is quite sensitive to change. However, due to its length, the SIP is inefficient
      and expensive to administer, and patient non-compliance is often a problem. The
      three questionnaires were compared according to the following factors:
      Acceptability: 97% of the patients favored the UW QOL scale compared with the SIP
      because it was more concise and easier to complete. VALIDITY: VALIDITY indicates
      the ability of the test under investigation to measure what it was intended to
      measure. Using the SIP as a gold standard, the UW QOL scale demonstrated an
      average criterion validity of 0.849, whereas the Karnofsky average criterion
      validity was 0.826. Reliability: Reliability is a measurement of the
      reproducibility of the data. The UW QOL questionnaire scored > 0.90 on
      reliability coefficients versus 0.80 for the Karnofsky and 0.87 for the SIP
      scale. Responsiveness: Responsiveness is the ability of the test to measure
      clinical change. The UW QOL scale faired better than the Karnofsky and the SIP
      scale in detecting change. The UW QOL scale is comparable to the Karnofsky and
      SIP scales when tested for validity and reliability. It was the preferred test
      format of 97% of patients and provided the greatest responsiveness to clinical
      change.

PMID- 8253556
TI  - Comparison of the addition of T and N integer scores with TNM stage groups in
      head and neck cancer.
AB  - The 1987 TNM classification system modified T and N definitions for squamous cell
      carcinomas of the head and neck. It did not change stage groupings (I through
      IV). The primary purpose of clinical staging is to divide patients into
      prognostically meaningful groups. The 1987 changes to the TNM T and N
      descriptions may not have removed the previously established heterogeneity within
      stage groups III and IV which existed before 1987. The development of a stage
      grouping system called TANIS (the T And N Integer Score), which is formed by
      adding the integer values of the T and N classifications, is reported herein. We
      compared the prognostic performance of T, N, TNM stage group, and TANIS stage for
      radiotherapy response and survival using data from 86 patients with newly
      diagnosed, measurable TNM II (oral cavity), and localized TNM III-IV squamous
      cell carcinomas of the head and neck, excluding nasopharynx, who were randomized
      to test 5-fluorouracil-methotrexate sequencing. The sequencing of chemotherapy
      was shown to make no difference to prognosis. All patients received 60 Gy of
      radiotherapy in 6 weeks. As compared to T, N, and the TNM stage group system,
      TANIS was the single best predictor for a complete response to radiotherapy (p =
      0.0005). TANIS was also the single best predictor for survival from randomization
      (p = 5 x 10(-6)). With the 86 patients divided into three groups (TANIS 2 to 3,
      4, and 5 to 7), TANIS provided a better prognostic discrimination than did the
      TNM stage grouping method (TNM II, III, and IV).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253558
TI  - Heterogeneity of salivary gland tumors studied by flow cytometry.
AB  - Intratumor DNA heterogeneity was investigated by flow cytometric analysis of
      multiple samples taken from different sites of 8 benign and 16 malignant
      primarily resected salivary gland tumors. All benign tumors had diploid DNA
      content. The overall incidence of DNA diploidy in 16 malignant cases examined was
      50%. Intratumor differences in DNA ploidy were observed in four malignant tumors
      (25%); 2 of these 4 heterogeneous tumors contained both aneuploid and diploid
      cell clones. The remaining 12 tumors showed a homogeneous DNA content in the
      different specimens; 8 were diploid, 3 aneuploid, and 1 was polypoid. The DNA
      nondiploid tumors were clinically more advanced than the DNA diploid ones (p <
      0.01). The tumor proliferation rate (fraction of cells in S-phase) was higher in
      DNA nondiploid samples than in diploid ones (p < 0.01). The DNA nondiploid tumors
      seemed to recur more often than DNA diploid ones did. The data emphasize the
      usefulness of DNA measurements for the characterization of malignant salivary
      gland tumors but also the importance of adequate sampling in assessing their DNA
      ploidy.

PMID- 8253557
TI  - Pilot trial of ribavirin for the treatment of laryngeal papillomatosis.
AB  - The antiviral drug ribavirin was used as an adjunct to laser surgery for the
      treatment of patients with laryngeal papillomatosis (LP). An uncontrolled
      clinical trial for four patients with ribavirin treatment at a daily dose of 23
      mg/kg was performed. Three adults received drug prior to laser surgery and
      continuing orally for 6 months. One infant was treated for 3 months. Two adults
      achieved complete remissions for at least 2 consecutive months, and both patients
      developed only minimal recurrent disease in 4 months of follow-up. The other
      adult and the child sustained a partial response and an increased interval
      between the required surgeries. Ribavirin caused only a mild, reversible
      reduction in hemoglobin and reticulocytosis. This preliminary trial shows that
      ribavirin may be an effective therapy in combination with surgery for LP in a
      larger controlled clinical trial.

PMID- 8253559
TI  - Infrahyoid myocutaneous flap in head and neck reconstruction.
AB  - Infrahyoid myocutaneous flap is one of the alternatives to be considered for the
      reconstruction of moderate defects following resection of the oral cavity,
      oropharynx, or hypopharynx cancers. The flap is based on the uni- or bilateral
      superior thyroid pedicle; its major limitations are due to small flap volume and
      arc of rotation. The authors reviewed a series of 15 consecutive patients with
      carcinomas of the oral cavity or pharynx who underwent radical surgical
      resections followed by immediate reconstruction using an infrahyoid myocutaneous
      flap. Four of five cases with prior irradiation presented complications. The
      incidence of flap necrosis in this series (47%) was higher than that reported by
      others (10%). We consider the presence of massive neck metastasis and prior
      irradiation contraindications to the use of this flap.

PMID- 8253560
TI  - Bacteriologic profile of surgical infection after antibiotic prophylaxis.
AB  - Wound infections resulting from contamination during major head and neck surgery
      continue to be a critical issue. In this study, specimens of pus or draining
      fluids from the wounds of 43 surgical patients who received perioperative
      administration of ampicillin/sulbactam or clindamycin were cultured for aerobic
      and anaerobic isolates to species level. Polymicrobial infections were identified
      in 13 of 43 patients (30%); 82% of isolates were aerobic organisms (45 of 55),
      and 18% were anaerobic or facultative species (10 of 55). Nine of 43 patients
      (21%) showed no bacterial isolates from cultured material. Independent of the
      primary site of malignancy or antibiotics used, nine of 25 isolates (36%)
      obtained from patients who underwent concomitant dental extractions, but only one
      of 24 (4%) who did not, developed anaerobic infections, (p < 0.001). The minimum
      inhibitory concentration of anaerobic isolates suggested sensitivity to the
      antibiotics used, and minimum bactericidal concentration data suggested that
      further postoperative doses may be required to adequately treat the heavily
      contaminated wounds. These data suggest that wound colonization following dental
      extraction procedures in clean contaminated head and neck surgery increases the
      risk of anaerobic infections. The use of a therapeutic dose and longer duration
      of perioperative antibiotics may be warranted.

PMID- 8253561
TI  - Symptom-directed selective endoscopy and cost containment for evaluation of head
      and neck cancer.
AB  - Panendoscopy is commonly used for diagnosing synchronous primary neoplasms of the
      head and neck, although the yield and cost effectiveness has been questioned. To
      compare symptom-directed selective endoscopy to panendoscopy, 100 consecutive
      patients with newly diagnosed and untreated squamous cell carcinoma were
      prospectively evaluated. Symptoms were used to select which studies might have
      been performed to discover synchronous primary lesions. All patients were
      subsequently evaluated with chest x-ray, barium esophagram, direct
      pharyngolaryngoscopy, esophagoscopy, and bronchoscopy with bronchial washings.
      Seven synchronous primary neoplasms were discovered in six patients with one
      patient having three separate tumors. There were five synchronous pharyngeal and
      one oral cavity neoplasms with two of the pharyngeal tumors being asymptomatic.
      Two primary cervical esophageal tumors and one synchronous esophageal tumor were
      found in three patients all of whom had symptoms of dysphagia and odynophagia.
      Two pulmonary metastasis were discovered by chest x-ray in patients with normal
      bronchoscopies with bronchial washings. Selective symptomatic evaluations would
      have resulted in one-third savings in total cost and would have minimized
      excessive procedures and potential morbidity. Direct pharyngolaryngoscopy and
      chest x-rays are recommended for patients with squamous cell carcinoma of the
      head and neck but esophagoscopy, esophagogram, and bronchoscopy might be reserved
      for patients with associated symptoms. Bronchial washings are not recommended.

PMID- 8253562
TI  - Papillary thyroid cancer in Mexico: review of 409 cases.
AB  - This is a retrospective review of 409 cases of papillary thyroid cancer treated
      at the Hospital of Oncologia, National Medical Center, IMSS in Mexico City. The
      clinical features, histopathologic findings, analysis of recurrences and
      survivals according to age, sex, tumor size, and modality of treatment are
      described. The results showed that tumoral diameter > 5 cm, distant metastasis at
      diagnosis, age > 40 years, and tumoral infiltration beyond the thyroid capsule
      significantly affect the patient's survival.

PMID- 8253564
TI  - Relative effect of surgery and radiotherapy on the internal jugular vein
      following functional neck dissection.
AB  - We examined the internal jugular veins in three groups of patients who had
      undergone (1) a functional neck dissection and radiotherapy, (2) a functional
      neck dissection alone, or (3) radiotherapy alone, using a noninvasive color
      Doppler ultrasound scan. The internal jugular veins were ultrasonically
      bilaterally normal in 18% of patients who had undergone a functional neck
      dissection and radiotherapy, in 88% of patients who had undergone a functional
      neck dissection alone, and in 57% of patients who had undergone radiotherapy
      alone. The combination of a functional neck dissection and radiotherapy
      significantly affected the internal jugular vein when compared with a functional
      neck dissection alone.

PMID- 8253563
TI  - Intracranial pressure changes during bilateral radical neck dissections.
AB  - The management of the contralateral neck in patients with head and neck cancer
      who have undergone a radical neck dissection (RND) is controversial. A number of
      these patients will require a second RND. Sacrifice of both internal jugular
      veins (IJV) has been felt to lead to increased intracranial pressure (ICP) with
      subsequent neurologic sequelae. From 1987 to 1991 four patients had staged
      bilateral RNDs at the West Virginia University. In these patients a subarachnoid
      bolt was placed to directly monitor ICP. Jugular bulb, mean arterial, pulmonary
      artery, and central venous pressures were monitored. Electroencephalographic
      (EEG) monitoring was also performed. All patients demonstrated elevations in ICP
      immediately on head rotation. Further marked elevations were noted immediately
      after IJV ligation with a maximum peak at 30 minutes. Pressure levels of greater
      than 40 mm Hg were observed in three of four patients. Systemic hypertension was
      observed in response to elevated ICP (Cushing's reflex). All patients studied
      recovered from surgery without significant sequelae. Within 24 hours the ICP had
      returned to normal in all patients. Three patients required intraoperative
      intervention to lower their ICP. We demonstrate that even in a staged second RND
      there are significant rises in ICP. These are to a level that suggests emergency
      medical intervention is required. We feel that when the second IJV is sacrificed
      an increase in ICP should be anticipated, monitored, and treated accordingly.

PMID- 8253565
TI  - Professional burnout among head and neck surgeons: results of a survey.
AB  - Burnout may develop in highly productive, hard-working individuals from all walks
      of life. Extending working hours under stressful circumstances may produce a
      sense of frustration resulting in emotional exhaustion, loss of empathy for
      patients, and a decreased sense of personal accomplishment. The membership of the
      American Society of Head and Neck Surgery and the Society of Head and Neck
      Surgeons was surveyed by mail relative to burnout. A total of 395 head and neck
      surgeons responded. Mean age was 48 years. The average individual worked an
      average of 66 hours per week. More than 70% of work was devoted to patient care
      of which 30% to 50% was devoted to the management of head and neck cancer. A
      total of 128 (34%) individuals responded that they felt "burned out." Only 27%,
      however, indicated frustration with disease, whereas 67% indicated frustration by
      government and 58% indicated frustration by the economics of medical practice.
      Most respondents enjoy their work, nevertheless, the stress of extending working
      hours dealing with severely ill patients, and the increased need to deal with
      government and economic issues is of concern to the community of physicians
      practicing head and neck surgery. Discussion about and confrontation with these
      issues are appropriate to facilitate and enhance an individual's ability to
      continue to function productively in this environment.

PMID- 8253566
TI  - Cervical manifestations of fibrosing mediastinitis: a diagnostic and therapeutic
      dilemma.
AB  - Fibroinflammatory and fibrosclerosing lesions involving the head and neck outside
      the thyroid and orbit are exceedingly rare. We present two cases of
      fibroinflammatory and fibrosclerosing lesions originating in the mediastinum
      which extended superiorly to involve soft tissues of the neck. These cases
      indicate that a subset of fibroinflammatory and fibrosclerosing lesions found in
      the head and neck originate in the mediastinum.

PMID- 8253567
TI  - Spontaneous infarction of parathyroid adenoma: case report and literature review.
AB  - A patient with asymptomatic primary hyperparathyroidism who spontaneously became
      normocalcemia is reported. The only significant finding was that of pain and
      tenderness in the enlarged parathyroid gland 2 weeks prior to surgery. This was
      due to a recent infarction of a parathyroid adenoma.

PMID- 8253568
TI  - Anatomic considerations in approaches to the mandible.

PMID- 8253569
TI  - Thyroid mass.
AB  - In addition to the history given in this case the consultants ask for information
      regarding a family history of thyroid cancer or exposure to irradiation. An FNA
      is in order all the time (Dr. Fredrickson), only if there is no history of
      irradiation (Dr. Clark), and repeatedly if the mass is cystic (Dr. Harvey). All
      concur with thyroid suppression if the FNA and thyroid scan support a benign
      diagnosis. With an FNA report of a "follicular neoplasm" the consultants state
      that the pathologist should narrow down the histology further. But coupled with
      the cold nodule on thyroid scan, a lobectomy is in order. All would proceed with
      a lobectomy and rely on frozen section before going further. If the mass is
      malignant on frozen section a completion total thyroidectomy is in order. With a
      frozen section report of papillary follicular carcinoma all agree that a total
      thyroidectomy is in order. The management of the lymph nodes varies with removal
      of the ipsilateral lymph nodes (Dr. Clark), bilateral paratracheal lymph node
      dissection (Dr. Fredrickson), or a sampling of adjacent lymph nodes including
      those in the mediastinum (Dr. Harvey). A neck dissection is in order only if some
      of the lymph nodes are positive for tumor. Two experts (Drs. Clark and Harvey)
      are never comfortable losing a parathyroid gland. If one is found it should be
      autotransplanted into the sternocleidomastoid muscle (Dr. Clark) or the
      brachioradialis (Dr. Harvey). While every attempt should be made to identify and
      preserve all the parathyroid glands another expert believes that one parathyroid
      gland is probably enough to sustain normal hormone levels (Dr.
      Fredrickson).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8253570
TI  - Continuous improvement in radiation protection.

PMID- 8253571
TI  - Application of airborne gamma spectrometric survey data to estimating terrestrial
      gamma-ray dose rates: an example in California.
AB  - We examined the applicability of radioelement data from the National Aerial
      Radiometric Reconnaissance, an element of the National Uranium Resource
      Evaluation, to estimate terrestrial gamma-ray absorbed dose rates, by comparing
      dose rates calculated from aeroradiometric surveys of uranium, thorium, and
      potassium concentrations with dose rates calculated from a radiogeologic data
      base and the distribution of lithologies in California. Gamma-ray dose rates
      increase generally from north to south following lithological trends, with low
      values of 25-30 nGy h-1 in the northernmost 1 x 2 degrees quadrangles between 41
      and 42 degrees N to high values of 75-100 nGy h-1 in southeastern California.
      Lithologic-based estimates of mean dose rates in the quadrangles generally match
      those from aeroradiometric data, with statewide means of 63 and 60 nGy h-1,
      respectively. These are intermediate between a population-weighted global average
      of 51 nGy h-1 reported in 1982 by UNSCEAR and a weighted continental average of
      70 nGy h-1, based on the global distribution of rock types. The concurrence of
      lithologically and aeroradiometrically determined dose rates in California, with
      its varied geology and topography encompassing settings representative of the
      continents, indicates that the National Aerial Radiometric Reconnaissance data
      are applicable to estimates of terrestrial absorbed dose rates from natural gamma
      emitters.

PMID- 8253572
TI  - Guidelines on limits of exposure to static magnetic fields. International
      Commission on Non-Ionizing Radiation Protection.

PMID- 8253573
TI  - COMIDA: a radionuclide food chain model for acute fallout deposition.
AB  - A dynamic food chain model and computer code, named "COMIDA," has been developed
      to estimate radionuclide concentrations in agricultural food products following
      an acute fallout event. COMIDA estimates yearly harvest concentrations for five
      human crop types (Bq kg-1 crop per Bq m-2 deposited) and integrated
      concentrations for four animal products (Bq d kg-1 animal product per Bq m-2) for
      a unit deposition that occurs on any user-specified day of the year. COMIDA is
      structurally very similar to the PATHWAY model and includes the same seasonal
      transport processes and discrete events for soil and vegetation compartments.
      Animal product assimilation is modeled using simpler equilibrium models.
      Differential transport and ingrowth of up to three radioactive progeny are also
      evaluated. Benchmark results between COMIDA and PATHWAY for monthly fallout
      events show very similar seasonal agreement for integrated concentrations in milk
      and beef. Benchmark results between COMIDA and four international steady-state
      models show good agreement for deposition events that occur during the middle of
      the growing season. COMIDA will be implemented in the new Department of Energy
      version of the MELCOR Accident Consequence Code System for evaluation of
      accidental releases from nuclear power plants.

PMID- 8253574
TI  - Future role of the health physicist.
AB  - What is the future role of the health physicist? Ten external societal forces and
      five internal forces that may have significant impact on the health physics
      profession are presented. What changes are taking place in our profession that
      will shape the way we conduct our business? What changes are likely in
      technology, education and training? Methods of strengthening the educational area
      of our profession are proposed. Comments to the author are welcomed.

PMID- 8253575
TI  - Daily intakes of alkaline earth metals in Japanese males.
AB  - Diet samples were collected for two duplicate portion studies and one market
      basket study. 226Ra in the diet samples was determined by alpha spectrometry and
      daily intake was estimated as 23 mBq (0.62 pCi) per person. Other alkaline earth
      metals were determined by inductively coupled plasma atomic-emission
      spectrometry. Average mineral intakes of calcium, magnesium, strontium, and
      barium were 0.55 g, 0.21 g, 2.3 mg, and 0.39 mg, respectively. Element ratios
      magnesium:calcium 0.38, strontium:calcium 4.2 x 10(-3), barium:calcium 7.1 x 10(
      4), and 226Ra:calcium 1.1 x 10(-12) were found in the diet; these compared with
      element ratios in Japanese vertebrae of magnesium:calcium 0.1:1,
      strontium:calcium 3.1 x 10(-4), barium:calcium 2.7 x 10(-5), and radium:calcium
      2.6 x 10(-14). Observed ratios, defined as the element ratio in bone divided by
      the respective element intake ratio in Japanese males, were as follows: 226Ra
      0.02, magnesium 0.03, strontium 0.07, and barium 0.04.

PMID- 8253576
TI  - Kinetics of radiocesium sorption in lake sediments.
AB  - The sorption of radiocesium (137Cs) in sediments sampled from Lake Pamvotis of
      Ioannina was studied in a laboratory simulation. In a series of experiments, the
      kinetics of 137Cs sorption and 137Cs distribution profiles in sediment cores were
      investigated. The results have shown that a significant percentage of 137Cs (35%)
      is adsorbed in the sediments during the first 3 d, at a rate of 0.41 +/- 0.05 d
      1. The rest of 137Cs is adsorbed with the slower rate of 0.024 +/- 0.004 d-1.
      137Cs rapidly reaches (< 5 d) a depth that does not exceed 3.5 cm. The sorption
      of 137Cs was found to follow Freundlich's empirical law, which describes the
      adsorption of most substances in solution to solids.

PMID- 8253577
TI  - Spatial distribution of thoron and radon concentrations in the indoor air of a
      traditional Japanese wooden house.
AB  - A radon-thoron discriminative passive dosimeter has been developed that can
      estimate both radon (222Rn) and thoron (220Rn) concentrations at the same time.
      Two polycarbonate films are installed as solid-state nuclear track detectors in
      the dosimeter housing. One film registers alpha tracks originating from
      predominantly thoron and its progeny together with a small contribution from
      radon, and the other film registers alpha tracks originating from radon and its
      progeny together with a negligible contribution from thoron. The lower detection
      limit is estimated to be 2.9 Bq m-3 for the radon concentration and 9.0 Bq m-3
      for the thoron concentration for 2 mo exposure. Preliminary measurements from
      1991-1992, in a traditional Japanese wooden house located in Kyoto, indicated
      that the indoor thoron concentration increases exponentially as the interior mud
      (or plaster-coated) wall is approached. A soil-based plaster commonly used in
      Japanese wooden houses to fill walls (or as a surface coating on the walls) is
      the probable source of the indoor thoron. Since thoron is not measured by the
      usual radon measurements, and the majority of Japanese houses are made of wood,
      attention should be paid to indoor thoron and its decay products, which may give
      a significant fraction of the total natural radiation exposure to the general
      public.

PMID- 8253578
TI  - Areas of the United States with elevated screening levels of 222Rn.
AB  - As part of an Environmental Protection Agency/State cooperative program, 38 of
      the 48 contiguous states have successfully conducted probability-based surveys of
      indoor 222Rn. These surveys produced short-term screening measurements in
      approximately 55,000 randomly selected houses. An objective common to all surveys
      was to identify geographic regions within the state with elevated screening
      levels of 222Rn. This paper examines the survey results as they relate to this
      objective. The 38 states were partitioned into 225 geographic regions and summary
      statistics of 222Rn concentrations (e.g., arithmetic mean, geometric mean,
      percentage of houses exceeding a specified level) and associated 95% confidence
      intervals were calculated for each region. Twenty-four of the 225 regions had
      arithmetic means exceeding 222 Bq m-3 (6 pCi L-1); these are analyzed in detail.

PMID- 8253579
TI  - Predicting the annual concentration of indoor 222Rn from one or more short-term
      measurements.
AB  - Long-term and short-term measurements of indoor 222Rn from 480 houses located in
      eleven states were used to study the relationship between the annual living area
      average (ALAA) and 1) a single 2 d measurement and 2) the mean of multiple 2 d
      measurements (taken in different seasons). Of particular interest is the issue of
      using a short-term measurement(s) to predict the ALAA in a given house. The
      results indicate that with 95% confidence (approximately): 1) a single 2 d
      measurement gives an interval estimate of the true ALAA that is within a factor
      of 2.5 of the predicted ALAA; and 2) a mean of two 2 d measurements (taken in
      different seasons) gives an interval estimate that is within a factor of 2.2 of
      the predicted ALAA. If a more precise estimate of the ALAA is needed, then an
      alternative procedure to using 2 d measurements should be employed (e.g., measure
      the annual concentration directly).

PMID- 8253581
TI  - Intercomparison of activity size distributions of thoron progeny by alpha- and
      gamma-counting methods.
AB  - It is difficult to calibrate sampling devices using radon or thoron progeny or
      particles measuring 1-4 nm; therefore, an interlaboratory comparison is important
      to verify the performance of graded diffusion batteries for the activity size
      distributions of the "unattached" progeny. This paper describes the results of an
      interlaboratory comparison of 220Rn progeny size distributions using graded
      diffusion batteries by alpha- and gamma-counting methods with different data
      inversion schemes. Graded diffusion batteries designed at the Inhalation
      Toxicology Research Institute and at the Environmental Measurement Laboratory
      were used in the study. Screens and backup filters from the Environmental
      Measurement Laboratory-graded diffusion batteries were counted simultaneously in
      alpha counters for total alpha activities, and those of the Inhalation Toxicology
      Research Institute-graded diffusion batteries were counted in a gamma detector
      for gamma activities from 212Pb. Because of the different counting methods and
      data analysis procedures used, this interlaboratory study of 220Rn progeny allows
      a more rigorous way of testing instrument performance. 212Pb particles generated
      in well-controlled environments of oxygen, nitrogen, or oxygen with 1 ppm of
      nitrogen oxide were measured. In general, good agreement in activity size
      distributions was obtained from these two methods. Some differences observed in
      individual size spectra were attributable to the data inversion programs used in
      each laboratory. When the data were analyzed by the same computer program, most
      differences disappeared.

PMID- 8253580
TI  - Adsorption of 222Rn by open-faced and diffusion-barrier canisters at different
      conditions of temperature and humidity.
AB  - Open-faced and diffusion-barrier charcoal canisters were individually exposed to
      a fixed temperature, humidity, and radon concentration in a chamber for a period
      of 7 d. The radon progeny activity in the canister under study was measured every
      3 h. A total of 15 runs were made for the open-faced canisters and nine runs for
      the barrier canisters with temperatures and absolute humidities ranging from 15
      30 degrees C and 0-15 g m-3, respectively. In addition, several runs were made
      with the radon, temperature, and humidity changing during the 7 d. Results show
      that open-faced canisters adsorb radon up to 60% more efficiently at 15 degrees C
      than at 30 degrees C while the barrier canisters show little temperature
      dependence. The barrier canisters are much less sensitive to humidity effects
      than the open-faced canister. When used to measure the radon concentration in
      air, the open-faced canister integrates over a period of only approximately 48 h
      while the barrier canister integrates over a period of approximately 96 h. The
      short integration time and the interference of water adsorption by open-faced
      canisters indicate that the open-faced canisters should be used for exposure
      times of 48 h and no longer.

PMID- 8253582
TI  - Cleanup protocol for 226Ra-contaminated cobbly soil at UMTRA Project sites.
AB  - The nonuniform distribution of 226Ra and other radiological contamination of
      cobbly soil encountered on several Uranium Mill Tailings Remedial Action Project
      sites is presented and discussed, and the concomitant challenges to the intent
      and implementation of the U.S. Environmental Protection Agency's soil cleanup
      standards are noted. In response to technical assessments and information
      presented to the U.S. Nuclear Regulatory Commission by the U.S. Department of
      Energy, the Nuclear Regulatory Commission has recently resolved the dilemma by
      concluding that compliance with Environmental Protection Agency soil cleanup
      standards for cobby soil at Uranium Mill Tailings Remedial Action Project sites
      would be adequately attained using bulk radionuclide concentrations, instead of
      requiring that the radionuclide concentration of the finer soil fraction passing
      a #4 mesh sieve met the standards. A Nuclear Regulatory Commission-approved
      procedure developed for cobbly soil remediation is outlined and discussed. The
      site-specific implementation of this procedure at Uranium Mill Tailings Remedial
      Action Project sites containing cobbly soil is estimated to save millions of
      dollars.

PMID- 8253583
TI  - Simple system upgrades for outmoded health physics instrumentation.
AB  - Older radiation detection equipment used in Health Physics operations suffers
      from unreliable and outdated electronics, even when the radiation detectors,
      shielding, and mechanical components are still serviceable. Upgrading these
      systems through relatively simple interfaces to modern personal computers can
      provide a cost-effective solution to extend the life of these systems and provide
      state-of-the-art options for computer control and automation. This paper outlines
      the basic needs and requirements for this type of upgrade and describes three
      projects at University of Missouri--Columbia that have used this approach.

PMID- 8253584
TI  - Comments on metabolically consistent breathing rates.

PMID- 8253585
TI  - Re: Harmonization of radon jargon and units.

PMID- 8253586
TI  - Hour is not the SI unit for time.

PMID- 8253587
TI  - On overbadging.

PMID- 8253588
TI  - Is the concept of effective dose working in practice?

PMID- 8253589
TI  - Comments on the active instruments used in the AGS dosimetry study.

PMID- 8253591
TI  - Pacemakers, noninvasive. Procedure/checklist 460-0593 (May 1993).

PMID- 8253590
TI  - Defibrillator/monitor/pacemakers.
AB  - Combined defibrillator/monitors enable the operator to assess and monitor the ECG
      and rapidly deliver a defibrillating countershock to patients suffering from
      ventricular fibrillation during a cardiac arrest. In addition, these units
      provide synchronized cardioversion for treating other arrhythmias, such as
      ventricular tachycardia, and most now offer external noninvasive pacemaker
      capability for treating patients with ventricular bradycardia or asystole.
      Defibrillator/monitors are critical resuscitation instruments and must perform
      effectively to avoid the otherwise preventable death of a cardiac arrest patient.
      However, both ECRI and the Food and Drug Administration (FDA) continue to receive
      a large number of problem reports on these devices each year. Device failures can
      occur for such reasons as operator error, depleted or defective batteries, or
      component failures. We evaluated eight units--three intended for crash-cart use
      and four intended for portable use, all with noninvasive pacemaker capability
      either standard or as an option, as well as one portable physiologic patient
      monitor to which a defibrillator (with or without a pacing option) can be
      attached--from six manufacturers.* We also evaluated one stand-alone noninvasive
      pacemaker. Although we did not include automated external defibrillators (AEDs)
      in our study, two of the evaluated units have options that allow them to function
      as AEDs. We rated the seven crash-cart and portable
      defibrillator/monitor/pacemakers according to three primary applications: (1)
      general crash-cart use, (2) prehospital (emergency medical service [EMS]) use,
      and (3) in-hospital transport. They are rated either Acceptable or Acceptable-
      Not Recommended for these applications, based primarily on technical performance
      (including battery operation, which is especially important in portable units),
      characteristics (such as line-powered operation and portability), features (such
      as automatic documentation), and human factors design (especially ease of use);
      some are inappropriate for specific uses because of their respective limitations
      in these applications. The portable physiologic patient monitor is not rated, but
      is discussed.** All of the pacemakers available as components of the evaluated
      units are acceptable for use; however, in most cases, purchasing decisions should
      be made according to defibrillator/monitor needs. The stand-alone pacemaker is
      rated Unacceptable because of its numerous performance, safety, and human factors
      disadvantages and because, other than its being a stand-alone unit, it offers no
      advantages over the other evaluated pacemakers; see "The Zoll NTP-1000 Stand
      alone Noninvasive Pacemaker." Readers are cautioned not to base purchasing
      decisions on our ratings and rankings alone, but on a thorough understanding of
      the issues surrounding defibrillator/monitors and noninvasive pacemakers, which
      can be gained only by reading this study in its entirety.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8253592
TI  - Incompatibility of disposable heated-wire breathing circuits and heated-wire
      humidifiers.

PMID- 8253593
TI  - Risk of electric shock from patient monitoring cables and electrode lead wires.

PMID- 8253594
TI  - Risk of electric shock from Reliance Models 7700, 7720, and 7780 ophthalmic
      instrument stands and Models 980, 6100, and 7000 examination chairs.

PMID- 8253595
TI  - Spontaneously increasing output power in HGM Model 5 ophthalmic argon lasers.

PMID- 8253597
TI  - Base failure and caster collapse on GE AMX-4 mobile x-ray units.

PMID- 8253596
TI  - Metal fragments shed by Storz PREMIERE phacoemulsification units.

PMID- 8253598
TI  - Battery leaks from SpaceLabs Medical PC II patient monitors.

PMID- 8253599
TI  - Cytopathological and immunohistochemical study for estimating radiotherapeutic
      effects in uterine cervical cancer.
AB  - In order to estimate the effects of radiation on cancer tissue, cytopathological
      findings, BrdU labelling index (L.I.), tumor markers and C-myc oncogene products
      were examined in 30 patients of uterine cervical cancer, before radiation, at
      around 10Gy, 30Gy, 50Gy and at the end of the therapy. In order to assess the
      radiotherapeutic effects, the cytological, histological, immunohistological
      findings were evaluated by Papanicolaou's classification, Oboshi and Shimosato's
      grading system and BrdU L.I. In the cytology, the radiation effect, such as the
      enlargement and vacuolation of the nuclei and cytoplasm, was observed at around
      10Gy of radiation, and significantly increased at around 30Gy showing lysis of
      the cells and pyknosis of the nuclei. The histological observation recorded
      remarkable change in the cancer tissue at around 30Gy of radiation. The BrdU L.I.
      showed a meaningful decrease around 30Gy in the radiosensitive cases compared
      with the radioresistant cases. Moreover, immunohistochemical investigation
      indicated the location of SCC and SLX in the cytoplasm of the cancer cells and of
      C-myc product in the nuclei. A distinct radiation effect was found in the C-myc
      oncogene product at around 10Gy. Ras oncogene was not found in the adenocarcinoma
      cases investigated. From these findings it is concluded that BrdU L.I., revealed
      by immunohistological study, is the most suitable indicator to estimate the
      response of radiation in cancer cells of the uterine cervix and that C-myc
      oncogene product has the potentiality to be used as a prognostic factor in
      uterine cervical cancer treated by radiation therapy.

PMID- 8253600
TI  - Bcr-abl mRNA expression in patients with chronic myeloproliferative disorders-
      absence of bcr-abl fused clone except chronic myelocytic leukemia.
AB  - Bcr-abl mRNA expression was studied in patients with chronic myeloproliferative
      disorders (CMPD) by the reverse transcriptase-polymerase chain reaction (RT-PCR)
      method. A bcr-abl transcript was not found in any patient with polycythemia vera,
      essential thrombocythemia or primary myelofibrosis, suggesting that the bcr-abl
      rearranged clone is not present in CMPD other than chronic myelogenous leukemia
      (CML). In CML clinical and laboratory data were compared from three bcr-abl
      types: the bcr exon 2-abl exon 2 (B2-A2) type, bcr exon 3-abl exon 2 (B3-A2) type
      and the co-expression type. Age at diagnosis tended to be younger (p = 0.08) in
      the co-expression type, and the platelet count tended to be lower (p = 0.11) in
      the B2-A2 type. However, there was no difference in other data, including the
      duration of the chronic phase and the phenotype of blasts at blast crisis.

PMID- 8253601
TI  - Distribution of serum lipoprotein(a) levels--a non-parametric analysis.
AB  - The distribution of serum lipoprotein(a) [Lp(a)] concentration among Japanese
      male adults was evaluated using non-parametric methods. The following results
      were obtained. 1) Among healthy male adults undergoing a medical checkup, Lp(a)
      showed a highly skewed distribution towards the low level. The distribution could
      be regarded as a power normal distribution with the power order of 1/2. The
      median of Lp(a) level was 14.1 mg/dl (the 25th percentile was 6.2 mg/dl and the
      75th percentile was 26.7 mg/dl). 2) The values of serum Lp(a) in subjects with
      vasospastic angina distributed at a higher level than for subjects with normal
      coronary arteries as diagnosed by coronary angiography. 3) The observed serum
      Lp(a) concentration moved to a higher range as the number of branches with
      significant stenosis on the coronary angiography increased. 4) Serum Lp(a) was
      one of the risk factors for ischemic heart disease. Its odds ratio when the cut
      off value was set at 26.7 mg/dl or 30 mg/dl was 2.52 and 2.94, respectively.
      Information on the distribution of serum Lp(a) concentration is useful for
      estimating the coronary atherogenic factor.

PMID- 8253603
TI  - Modulation of gene expression during aging of human vascular endothelial cells.
AB  - Vascular endothelial cells are thought to play an important role in human aging
      as their senescence and detachment from a vascular wall may contribute to
      arteriosclerosis and high blood pressure in the elderly. We investigated the
      level of fibronectin (FN) expression in aortic endothelial cells aged in vivo,
      because FN is necessary for cell attachment and spreading and its increased
      expression had been shown in aging fibroblasts. The results showed that the
      steady state level of expression of FN mRNA increased with advancing donor age,
      while the labeling index of cultured cells decreased with age. Furthermore, the
      increased level of FN expression clearly correlated with an increase in cell
      area. In order to explore whether these changes reflected exhaustion of
      proliferation potential in vivo, we examined FN expression in human umbilical
      vein endothelial (HUVE) cells aging in vitro. Very similar results were obtained,
      supporting the idea that vascular endothelial cells age in vivo by using up
      division potential. Furthermore, we investigated the level of endothelin (ET) -1
      mRNA expression during in vitro cellular aging of HUVE cells. The results showed
      that the expression of ET-1 gene was also up-regulated when the culture became
      old. It is very interesting that the genes for quite different proteins of FN and
      ET-1 are both up-regulated during cellular aging.

PMID- 8253602
TI  - Ewing's sarcoma: evaluation of chemotherapy in 17 cases.
AB  - Seventeen patients with Ewing's sarcoma were divided into 3 groups according to
      treatment. Ten patients were treated with complete chemotherapy; 9 with VACA
      protocol, composed of vincristine, actinomycin-D, cyclophosphamide and
      doxorubicin, and the remaining 1 with T-11 protocol. Four were given incomplete
      VACA protocol, and another 3 received no chemotherapy. Clinical results were
      evaluated in the three treatment subgroups described above. All patients without
      systematic chemotherapy died from lung metastasis within 1 year of the initial
      treatment. Three of 4 patients who were given incomplete chemotherapy died after
      a mean survival period of 17.7 months, and one developed cancerous pleuritis
      after 38 months. In the group receiving complete systematic chemotherapy, 5 of 10
      patients are alive, and 2 have been disease-free for more than 3 years. Distant
      metastasis is likely when viable cells persist at the site of the primary tumor,
      even if the tumor size has been considerably reduced by preoperative
      chemotherapy. Therefore, immediate initiation of intensive chemotherapy and
      maintenance for the full course of therapy can improve the prognosis of Ewing's
      sarcoma.

PMID- 8253604
TI  - Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates
      to various antimicrobial agents. III. Novel, inducible resistance to macrolide
      lincosamide-streptogramin B (MLS) antibiotics.
AB  - Resistance patterns against 25 antimicrobial agents consisting of beta-lactams,
      aminoglycosides, tetracyclines, fluoroquinolones, macrolides and etc. were
      examined for 69 strains of methicillin-resistant Staphylococcus aureus (MRSA)
      isolated at Hiroshima University Hospital from July 1991 to April 1992. Regarding
      overall resistance (the percentage of highly and moderately resistant strains),
      the following antimicrobial agents were no more effective chemotherapeutics for
      MRSA infections (%resistance): methicillin (100), flomoxef (100), kanamycin
      (100), tobramycin (100), amikacin (100), isepamicin (100), gentamicin (78),
      dibekacin (100), ofloxacin (99), levofloxacin (99), temafloxacin (99),
      erythromycin (100), clarithromycin (100), tetracycline (93), minocycline (93) and
      fosfomycin (100). Further spread of arbekacin-resistant strain, which was
      isolated in April 1991, into a clinical environment could not be recognized
      during the period covered in the present study. All the MRSA strains were
      resistant either constitutively (26 strains) or inducibly (43 strains) to
      macrolide-lincosamide-streptogramin B (MLS) antibiotics. When expression is
      constitutive, the strains are resistant to all MLS antibiotics. In contrast, 16
      membered macrolide (i.e., jasamycin), lincomycin and mikamycin B escape
      resistance in the strains with a typical inducible resistance overcome in the
      presence of 14-membered macrolides by a translational attenuation mechanism.
      Three of 4 beta-lactamase-positive strains, however, can not be classified in
      these two resistance groups, being exclusively resistant to mikamycin B. The
      strains grown in the presence of any inducing MLS antibiotic became susceptible
      to mikamycin B even in the inducer-free culture.

PMID- 8253605
TI  - Adjuvant chemotherapy for patients with soft tissue sarcoma.
AB  - Forty patients with soft tissue sarcoma (Enneking's stage I and II) were treated
      in our department between 1965 and 1992. We administered VACA regimen (composed
      of vincristine, actinomycin-D, cyclophosphamide, and doxorubicin) to 14 of 40
      patients. Among 40 patients, the 5-year survival rate was 56% in 14 patients with
      chemotherapy and 39% in 26 without chemotherapy (p < 0.02). In 32 patients of
      Stage II, the 5-year survival rate was 40% in 11 patients with chemotherapy and
      31% without chemotherapy (p < 0.05). The improvement of the survival rate was due
      to delay in the development of lung metastases (chemotherapy group: 21.2 months
      after first visit, non-chemotherapy group: 9.4 months) and prolongation of the
      survival period after metastases (chemotherapy group: 26 months, non-chemotherapy
      group: 7.4 months).

PMID- 8253606
TI  - Retrograde cerebral and coronary perfusion for acute dissection of Stanford type
      A with destruction of the right coronary ostia.
AB  - Repair of acute aortic dissection with destruction of the right coronary ostia
      and aortic valve regurgitation is described. The patient was a 54 year-old female
      with Marfan syndrome, who was admitted to our hospital for acute dissection with
      annulo aortic ectasia, accompanied by myocardial ischemia of the inferior wall.
      Retrograde dissection to the aortic annulus and destruction of the right coronary
      ostia due to extended dissection were noted. Retrograde coronary infusion through
      the coronary sinus was conducted during replacement of aortic annulus by the
      Cabrol method in conjunction with supplementary vein grafting to the right
      coronary artery. Distal repair was carried out, supported by hypothermic
      circulatory arrest and retrograde cerebral perfusion through the superior vena
      caval cannula. Retrograde cerebral and coronary sinus perfusion have been shown
      to be quite effective for treating patients requiring complex reconstruction of
      the ascending aorta.

PMID- 8253607
TI  - Spontaneous cure of acute bronchitis caused by Chlamydia pneumoniae in a 15-year
      old boy.
AB  - Chlamydia pneumoniae was isolated from the pharyngeal swab of a 15-year-old
      patient with acute bronchitis. The serum IgM antibody against C.pneumoniae was
      elevated up to 160-fold in the acute phase and decreased to 20-fold in the
      convalescent phase using the microimmunofluorescence (MIF) test. IgG antibody
      titers in the acute phase and the convalescent phase were 40-fold and 160-fold
      respectively using the MIF test. The patient recovered from the bronchitis
      without any effective treatment, indicating spontaneous cure of the disease.

PMID- 8253608
TI  - A case report of epithelioid leiomyosarcoma of transverse mesocolon: diagnosis
      and treatment.
AB  - A case of epithelioid leiomyosarcoma of the transverse mesocolon in a 45-year-old
      man was reported. The patient had a rapidly growing mass in the left upper
      quadrant. Ultrasonography, gastrointestinography, and abdominal computed
      tomography showed that the mass was separated from the pancreas, the
      gastrointestinal tract, and the retroperitoneal organs. Preoperatively the
      primary origin of this tumor was related to the transverse mesocolon. On
      laparotomy the tumor of 5cm by 6cm by 3cm in size was found in the anterior left
      of the transverse mesocolon and the mass was resected entirely. The patient is
      well 18 months after surgical treatment with no evidence of recurrence.

PMID- 8253609
TI  - Keeping vigil over US cattle for BSE.

PMID- 8253610
TI  - Protozoal abortion in cattle.

PMID- 8253611
TI  - More on self-mutilative behavior in horses.

PMID- 8253612
TI  - Finds writings of animal rights activists offensive.

PMID- 8253613
TI  - Feral cats.

PMID- 8253614
TI  - Veterinarian in a local health department.

PMID- 8253615
TI  - Virus-induced maternal reproductive failure of swine.

PMID- 8253616
TI  - What is your diagnosis? Retinal detachment.

PMID- 8253617
TI  - What is your neurologic diagnosis? Neoplasm of right brachial plexus.

PMID- 8253618
TI  - Animal behavior case of the month. Aggression toward a neonatal foal by its dam.

PMID- 8253619
TI  - Nonveterinary ownership of veterinary clinics.

PMID- 8253620
TI  - Cutaneous histamine reactivity, histamine content of commercial allergens, and
      potential for false-positive skin test reactions in dogs.
AB  - The cutaneous reactivity of normal and atopic dogs to intradermal injections of
      histamine phosphate was evaluated. Significant differences were not found in the
      mean wheal diameters of either group. Commercial allergens used for intradermal
      skin testing and immunotherapy were determined to contain histamine. To determine
      whether allergen histamine content was sufficient to cause false-positive skin
      test results, the cutaneous response of Johnson grass allergic dogs was compared,
      using commercial Johnson grass allergen and commercial Johnson grass allergen
      with histamine removed. Significant differences were not noticed between Johnson
      grass and dehistaminized Johnson grass. Therefore, the histamine content of
      commercial Johnson grass allergen did not appear to cause false-positive skin
      test results for this group of Johnson grass allergic dogs.

PMID- 8253621
TI  - Use of ultrasonography and secondary wound closure to facilitate diagnosis and
      treatment of a cranial mediastinal abscess in a dog.
AB  - A 3-year-old dog was examined because of acute, severe respiratory distress.
      Harsh inspiratory sounds, oral abrasions, and pyrexia were identified. On
      thoracic and cervical radiographs, the trachea appeared to be ventrally displaced
      and narrowed for several centimeters of its length at the thoracic inlet.
      Cytologic examination of a transcutaneous aspirate from the caudal cervical
      region revealed a neutrophilic exudate with extracellular bacteria. The
      ultrasonographic appearance of the thoracic inlet lent support to a diagnosis of
      cranial mediastinal abscess. Drainage and debridement of the abscess was
      accomplished via a ventral midline cervical approach, and the site was managed as
      an open wound. After 6 days, secondary wound closure was performed. The ventral
      cervical approach prevented contamination of the pleural space, and treatment as
      an open wound allowed inspection of the affected tissues to determine optimal
      time for wound closure. The cause of this cranial mediastinal abscess was
      unknown.

PMID- 8253622
TI  - Systemic mycosis caused by Acremonium sp in a dog.
AB  - A 4-year-old female German Shepherd Dog was examined to determine the cause of
      ataxia, progressive head tilt, anorexia, lethargy, and weight loss of 3 weeks'
      duration. A vestibular syndrome, generalized lymphadenopathy, bilateral uveitis,
      and chorioretinitis with complete detachment of the left retina were detected.
      Abnormal clinicopathologic findings were isosthenuria and hyperglobulinemia. The
      non-functional left eye was enucleated and fungal organisms resembling
      Aspergillus spp were identified on histologic examination. Microbial culture of a
      urine sample yielded Acremonium sp, which was initially considered a contaminant.
      The dog was considered to have systemic aspergillosis and was treated with
      itraconazole for 7 months, until it was euthanatized because of persistent
      vomiting and anorexia. Postmortem examination revealed multisystemic
      pyogranulomatous and necrotizing inflammation of the myocardium, pericardium,
      liver, and kidneys; and granulomatous splenitis, lymphadenitis, retinitis,
      endometritis, and meningoencephalitis. Fungal culture of affected organs yielded
      Acremonium sp. These findings indicated that Acremonium spp can be pathogenic and
      should not be ignored when cultured.

PMID- 8253623
TI  - Malignant histiocytosis in a cat.
AB  - A 13-year-old male domestic shorthair cat was found to have normocytic
      hypochromic regenerative anemia, lymphopenia, eosinopenia, thrombocytopenia,
      hyperglycemia, hyperbilirubinemia, and a prolonged activated partial
      thromboplastin time. Transfusions of packed RBC failed to maintain the PCV above
      13% for > 8 hours. The cat was euthanatized. At necropsy, the spleen liver, lymph
      nodes, and bone marrow were infiltrated with malignant histiocytes undergoing
      erythrophagocytosis.

PMID- 8253624
TI  - Treatment of gastric dilatation-volvulus and a rapid method for prevention of
      relapse in dogs: 134 cases (1988-1991)
AB  - During a 3.3-year period, gastric dilatation-volvulus was diagnosed in 134 dogs.
      Thirteen of them died or were euthanatized prior to treatment. In 33 dogs,
      decompression and emptying of the stomach was successfully performed via a
      gastric tube. Rate of recurrence was 75.8% (25/33) for these dogs. Eighty-eight
      dogs were treated surgically. In all but 1 surgically treated dog, a new
      technique for gastropexy was performed for prevention of relapse. For the 5-cm
      long gastropexy, the pyloric antrum was incorporated in the cranial suture of the
      abdominal wall. Of the surgically treated group, 63 dogs (79.7%) were discharged
      from the clinic in good condition. Recurrence of gastric dilatation, without
      evidence of gastric volvulus, 2 (n = 3) and 6 (n = 1) months after surgery, was
      observed in 6.6% (4/61) of surgically treated dogs with gastric dilatation
      volvulus. Four (6.6%) of the 61 dogs died or were euthanatized because of other
      causes, but had been without signs of gastric dilatation within a mean of 19
      months after surgery. In the remaining 53 dogs (86.8%), relapse had not been
      observed by the end of the follow-up period. In dogs with surgical treatment of
      gastric dilatation-volvulus, recurrence rate (6.6%) was significantly (P <
      0.0001) different from that in those with medical treatment (75.8%). This study
      indicated that recurrence of gastric dilatation-volvulus may be prevented with
      this simple and fast gastropexy technique.

PMID- 8253625
TI  - Use of a bovine hemoglobin preparation in the treatment of cyclic ovarian
      hemorrhage in a miniature horse.
AB  - Anemia that was secondary to ovarian hemorrhage in a 4-year-old miniature horse
      mare was treated prior to laparotomy with polymerized ultrapurified bovine
      hemoglobin (PUBH). Two previous whole-blood transfusions had resulted in acute
      transfusion reaction, and a suitable blood donor could not be found among 9
      horses, necessitating use of the blood substitute. Subsequent blood typing
      revealed the mare to be Aa-negative, with allo-antibodies against Aa in serum.
      Serious adverse reactions were not observed after infusion of PUBH, and the mare
      recovered. Although the safety and efficacy of using PUBH in horses has not been
      established, PUBH may prove to be an excellent alternative to whole-blood
      transfusions, when indicated.

PMID- 8253626
TI  - Transection of the pelvic flexure to reduce incarceration of the large colon
      through the epiploic foramen in a horse.
AB  - A 7-year-old Thoroughbred mare underwent exploratory celiotomy for diagnosis and
      treatment of colic. An irreducible herniation of the large colon through the
      epiploic foramen was found. To reduce the hernia, the pelvic flexure was
      transected and the ends of the large colon were closed. The intercolonic
      mesentery was divided, and unaffected left ventral colon was moved into the
      epiploic foramen, providing sufficient space so that affected left dorsal colon
      could be reduced. The affected left ventral colon was then reduced and the
      diseased portion of both colons was resected. The colons were resected. The
      colons were rejoined with an end-to-end anastomosis.

PMID- 8253627
TI  - Isolation of multiple Salmonella serovars from a dairy two years after a clinical
      salmonellosis outbreak.
AB  - Samples were obtained for bacteriologic culturing of salmonellae from cows and
      calves on, and the environment of, a large California dairy that used free-stall
      housing and a flush system for manure handling. Two years previously, the dairy
      had an outbreak of clinical salmonellosis in the lactating herd; however, since
      that time, it had not had problems with clinical salmonellosis. On the basis of
      mean annual milk production per cow, this dairy was consistently ranked in the
      top 25% of dairies in the area enrolled in the Dairy Herd Improvement
      Association. Results of bacteriologic culture of 76% (108/142) of environmental
      samples and 48% (639/1,339) of fecal samples were positive for salmonellae.
      Eighty-two percent of the isolates were serovar C1, subclassified as Salmonella
      montevideo, and 17% were serovar E. Results of bacteriologic culture of 85% of
      samples of recycled flush water being pumped into the free-stall alleys were
      positive, as were results of bacteriologic culture of 78% of samples of herd bulk
      milk filters, 97% of fecal samples collected from calves being fed nonsalable
      milk, and 25% of fecal samples collected from cows at the time of breeding. These
      findings suggest that freedom from clinical salmonellosis and comparatively high
      measures of herd performance do not indicate the absence of salmonellae from a
      premises, and that hardy infectious agents transmitted by ingestion of feces can
      become established in the environment of modern free-stall dairies that use
      recycled water in their manure flush systems.

PMID- 8253628
TI  - Conjunctivitis and keratoconjunctivitis associated with chlamydiae in swine.
AB  - Two swine herds housed in confinement had high prevalences of conjunctivitis and
      keratoconjunctivitis. Necropsies were performed on 7 pigs (2 to 8 weeks old) with
      mucopurulent conjunctivitis from one farm and on 1 sow with keratoconjunctivitis
      from another farm. Histologically, the small pigs had lymphoplasmacytic
      conjunctivitis with mild lymphofollicular hyperplasia. The sow had marked
      conjunctival lymphofollicular hyperplasia and ulcerative keratitis with
      neovascularization. Ultrastructural examination of conjunctival specimens from
      the pigs and sow revealed chlamydiae, often associated with glycogen within
      intracytoplasmic vacuoles in conjunctival cells. The identity of the chlamydiae
      isolated from 2 necropsied pigs as well as from conjunctival swab specimens from
      other pigs on the same farm was unknown. It is possible that the chlamydiae seen
      ultrastructurally within intracytoplasmic vacuoles containing glycogen in
      conjunctival cells were Chlamydia trachomatis. Results of this investigation
      suggested an etiologic role, at least in part, for chlamydiae in the disease
      process of these swine. On the basis of ultrastructural findings, mycoplasmal
      coinfection could not be ruled out. Several pigs also had cytomegalic inclusion
      virus rhinitis.

PMID- 8253629
TI  - Neonatal septicemia in calves: 25 cases (1985-1990).
AB  - Historical, physical, and clinicopathologic findings in 25 septicemic calves were
      examined to further characterize the clinical features of naturally induced
      bovine neonatal septicemia. Owners often reported single organ disease, but
      physical examination revealed multiple organ disease in more than half the
      calves. A third of the calves were admitted as representative of a herd problem.
      Laboratory findings were variable, but commonly included changes in the
      differential WBC count and plasma fibrinogen concentration. Low serum
      immunoglobulin concentrations were found in approximately half the calves.
      Escherichia coli was the most frequently isolated organism, but gram-positive
      infections were found in 10%, and polymicrobial infections in 28%, of the calves.
      Previous antimicrobial administration did not appear to affect culture yield. At
      necropsy, lesions were seen in multiple organs in most calves. The respiratory
      and gastrointestinal systems were most commonly affected. Few of the calves had
      umbilical infections. The survival rate was poor (< 12%).

PMID- 8253630
TI  - Gender differences in the acquisition of salary negotiation skills: the role of
      goals, self-efficacy, and perceived control.
AB  - The authors examined the effectiveness of different training programs in men's
      and women's acquisition of salary negotiation skills. MBA students received a 2
      stage training program that provided initial content instruction in negotiation
      tactics, followed by supplemental training in either goal setting or self
      management. After both training sessions, participants conducted salary
      negotiations with trained confederates who used standardized guides to award
      salary increases. Results indicated that, although women negotiated lower
      salaries than men following the initial training, controlling for goals
      eliminated this difference. Analysis of salary improvements following
      supplemental training revealed that gender differences were reduced for self
      management participants only. Changes in perceived control over the negotiation
      appeared to mediate this effect. Implications of these findings for understanding
      training effectiveness are discussed.

PMID- 8253631
TI  - Commitment and employee behavior: comparison of affective commitment and
      continuance commitment with perceived organizational support.
AB  - The social exchange view of commitment (R. Eisenberger, R. Huntington, S.
      Hutchison, & D. Sowa, 1986) suggests that employees' perceptions of the
      organization's commitment to them (perceived organizational support, or POS)
      creates feelings of obligation to the employer, which enhances employees' work
      behavior. The authors addressed the question of whether POS or the more
      traditional commitment concepts of affective commitment (AC) and continuance
      commitment (CC) were better predictors of employee behavior (organizational
      citizenship and impression management). Participants were 383 employees and their
      managers. Although results showed that both AC and POS were positively related to
      organizational citizenship and that CC was negatively related to organizational
      citizenship, POS was the best predictor. These findings support the social
      exchange view that POS creates feelings of obligation that contribute to
      citizenship behaviors. In addition, CC was unrelated, whereas AC and POS were
      positively correlated, with some impression management behaviors.

PMID- 8253632
TI  - Sympathy and support for industrial actions: a justice analysis.
AB  - The authors investigated the effects of different causes of grievance and
      different types of industrial action on observers' justice perceptions and their
      sympathy toward and support for grievants in industrial actions. Results
      indicated that grievances based on interactional injustice generated a stronger
      perception of unfairness, more sympathy, and more support than did grievances
      based on procedural injustice, which in turn generated a stronger perception of
      unfairness, more sympathy, and more support than did grievances based on
      distributive injustice. Ss also expressed less support for strikes than for sit
      ins, but no such difference because of the types of industrial action taken was
      found for perceived fairness and sympathy. Finally, the ratings on perceived
      fairness, sympathy, and support were more discrepant among the three types of
      grievance for sit-ins than for strikes.

PMID- 8253633
TI  - A cross-level units-of-analysis approach to individual differences in skill
      acquisition.
AB  - A recent multiple-stage model posits that the individual-difference factors
      influencing performance vary depending on skill acquisition stage (P. L.
      Ackerman, 1989, 1990). In the current study, the authors examine the effect of
      ability in early skill acquisition and extend earlier research by examining the
      roles of self-efficacy and task familiarity. Furthermore, learning-curve modeling
      with multilevel models is used to alleviate prior analytical problems. Subjects
      (N = 115) performed an air traffic control simulation task. Nonlinear learning
      curve parameters were estimated for each subject using a negative exponential
      model (see D. R. Rogosa & J. B. Willett, 1985). Cognitive ability, self-efficacy,
      and task familiarity were then used to predict learning-curve parameters:
      learning-rate constant and asymptotic performance. Results revealed that ability,
      self-efficacy, and familiarity predicted the learning-rate constant, whereas self
      efficacy predicted asymptotic performance.

PMID- 8253634
TI  - Relationship of client abuse with locus of control and gender: a longitudinal
      study in mental retardation facilities.
AB  - Direct-care workers (158 women and 154 men) participated in a study of aggressive
      work behavior. Employees completed J. B. Rotter's (1966) Locus of Control Scale.
      Client abuse data were collected over a 2-year period. Individuals reporting
      higher levels of external locus of control and men were more likely to emit
      aggressive behavior than were people reporting lower levels of external locus of
      control and women. Results supported the hypotheses and suggested that individual
      and group differences may be useful in understanding maladaptive, aggressive work
      behavior.

PMID- 8253635
TI  - What's in a name? The moderating role of public self-consciousness on the
      relation between brand label and brand preference.
AB  - Products with bargain-brand labels are generally considered to be cheap or
      inferior in comparison with products with national brand labels. Publicly self
      conscious individuals might accept products with national brand labels and reject
      products with bargain brand labels to enhance their public images. A field
      experiment was conducted to test this hypothesis. Three hundred twenty adults,
      frequenting public locations, tasted and rated either national brand or bargain
      brand peanut butters that had either national brand or bargain brand labels. They
      also completed the Public Self-Consciousness scale (A. Fenigstein, M. F. Scheier,
      & A. H. Buss, 1975). Ratings of products with national brand labels were expected
      to be positively correlated with level of public self-consciousness, whereas
      ratings of products with bargain brand labels were expected to be negatively
      correlated with level of public self-consciousness. The author's results
      confirmed both predictions.

PMID- 8253636
TI  - Type A behavior pattern and escalating commitment.
AB  - Subjects (N = 98) were randomly assigned to high- and low-responsibility
      conditions in a commitment-escalation experiment. Global Type A behavior pattern
      and the underlying dimension of achievement strivings were positively related to
      the desire to continue the same course of action in the high prior-responsibility
      condition but not in the low prior-responsibility condition. These findings are
      discussed in terms of future research into the judgment processes of people with
      Type A personality and the possible role of escalating commitment in disorders
      experienced by people with Type A personality.

PMID- 8253637
TI  - The beginning ... condensed notes of events leading to and the development of the
      Arkansas Area Health Education Centers.

PMID- 8253638
TI  - Continuing education.

PMID- 8253639
TI  - What is an AHEC "worth" to a community hospital.

PMID- 8253640
TI  - The AHEC libraries.

PMID- 8253641
TI  - Research at the Area Health Education Centers.

PMID- 8253642
TI  - Arkansas AHEC family practice residency programs. A progress report.

PMID- 8253643
TI  - Addressing Arkansas' rural primary care challenges.
AB  - Universal health coverage may become a reality by the year 2000 and implies a
      greater need for primary care physicians in rural Arkansas in the 21st century.
      We can start this decade to build the capacity for an outstanding rural primary
      care system for the next century. The number of rural primary care physicians can
      be increased by 1) placing a high priority on recruiting more students to primary
      care, 2) improving the attractiveness of rural practice, and 3) improving the
      long-term financial viability of rural primary care. The quality of rural primary
      care will be greatly influenced by changes in information technology. Medical
      outreach activities from urban centers to rural communities and changes in rural
      medical infrastructures will be necessary as we approach the year 2000.

PMID- 8253644
TI  - Area Health Education Centers & College of Health Related Professions. A
      partnership to solve health care shortages.

PMID- 8253645
TI  - Arkansas AHEC program. Past and future.

PMID- 8253646
TI  - The development of clinical pharmacy practice in the Arkansas AHEC program.

PMID- 8253647
TI  - Nurse education in the Arkansas AHEC program.

PMID- 8253648
TI  - Radiological case of the month. Lipoid pneumonia.

PMID- 8253649
TI  - Femoral head perfusion in patients with femoral neck fracture and femoral head
      necrosis.
AB  - Femoral head perfusion in adults was studied by superselective i.a. DSA in 35
      normal subjects, in 9 patients with medial femoral neck fracture preoperatively,
      and in 36 patients with femoral head necrosis before bone grafting, and as
      therapeutic control after grafting. All patients with femoral neck fracture
      showed an interruption of the proximal nutrient branches. In 93% of the cases
      with femoral head necrosis, these branches were rarefied or the medial circumflex
      femoral artery was interrupted. Postoperative DSA after pedicled pelvic bone
      graft revealed a regularly perfused graft in 82%. Superselective i.a. DSA is a
      valuable procedure for the therapeutic decision in selected patients with femoral
      neck fracture as well as before pedicled pelvic bone grafting and as therapeutic
      control after grafting.

PMID- 8253650
TI  - The variable of hypertrophic changes in hepatic morphology: CT appearance.
AB  - The liver has a particular ability to regenerate and demonstrate hypertrophy
      under several circumstances. The aim of this essay is to illustrate the computed
      tomographic (CT) appearances of the hypertrophic changes in hepatic morphology
      and to focus on the broad spectrum of etiologies. One thousand seven hundred and
      twenty-one patients who had CT of the abdomen were retrospectively studied. One
      hundred and fifty-three (9% of them (82 men, 71 women), with a mean age of 50
      years (range: 18 to 87 years), had hypertrophic changes in the liver. The
      different final diagnoses included liver cirrhosis (n = 75), Budd-Chiari syndrome
      (n = 35), partial hepatectomy (n = 25), cholangiocarcinoma (n = 10), liver
      metastasis (n = 1), preoperative portal vein embolization (n = 3),
      schistosomiasis (n = 1), and congenital hypertrophy (n = 3). Hypertrophic changes
      in hepatic morphology are not uncommon conditions and CT is likely to afford the
      opportunity to detect them. The discovery of such an abnormality must prompt the
      radiologist to eliminate the possibility of neoplastic etiology or underlying
      portal hypertension.

PMID- 8253651
TI  - Adamantinoma of the tibia: MRI documentation.
AB  - We report two cases of adamantinoma of the tibia, for which an MR examination was
      performed. Each patient was initially investigated with plain radiography and in
      case 2, a computerized tomography was also performed. The MR characteristics of
      this tumor are scarcely documented in the even few case reports of this tumor.
      MRI does not add to the (differential) diagnosis but does have significance in
      the preoperative staging because it allows adequate delineation of tumor, which
      is essential for a complete and curative resection of the tumor.

PMID- 8253652
TI  - [Fractures due to sacral insufficiency].
AB  - Seven instances of insufficiency fractures of the sacrum due to metabolic bone
      disease or secondary to pelvis radiation therapy were retrospectively reviewed.
      The contribution of the different investigation procedures was compared.
      Identification of stress fractures during clinical investigation or in the
      assessment of metabolic disease should enable early and adequate response and
      possibly prevent unnecessary biopsies.

PMID- 8253653
TI  - Localized pleural mesothelioma.
AB  - The clinical and radiological presentation of five anatomo-pathologically proven
      cases of localized pleural mesothelioma are described. In all patients
      conventional chest films and CT scans were performed. Two patients had also an MR
      examination. On conventional chest films all lesions presented as sharply defined
      homogeneous masses. In most cases there was inhomogeneous contrast enhancement on
      CT. In two cases calcifications and pleural effusion were present. There was no
      chest wall invasion, nor mediastinal adenopathy. On MR T1-weighted images, the
      tumor had an intermediate to high signal intensity. In the one case in which T2
      weighted sequences were performed, tumor signal intensity increased compared to
      that on T1-weighted images. In contrast to what is generally found in literature
      and probably because the series contained rather large masses, most patients had
      symptoms while the mass was inhomogeneous on CT. Conventional chest films
      together with CT and MRI are helpful in differentiating this entity from
      malignant mesothelioma. However, focal areas of malignant degeneration cannot be
      excluded radiographically.

PMID- 8253654
TI  - Achalasia-alacrima-ACTH insensitivity syndrome (Triple-A-syndrome).
AB  - Achalasia is a rare pathology in infancy. It is still more infrequent when
      associated with adrenal insufficiency and alacrima, a disorder known as
      Allgrove's syndrome, the etiology of which remains unclear. We describe a 9-year
      old girl who presents with glucocorticoid insufficiency, partial
      mineralocorticoid deficiency, achalasia, and alacrima.

PMID- 8253655
TI  - Solitary plasmacytoma of the greater sphenoid wing with secondary submandibular
      soft tissue metastasis.
AB  - We report the follow-up of a case of solitary plasmacytoma of bone in the
      posterolateral orbital wall previously published in this journal. The patient
      presented three years after initial diagnosis and treatment with a submandibular
      soft tissue metastasis, probably in a lymph node. Reports of lymph node
      metastases from solitary plasmacytoma of bone are rare.

PMID- 8253656
TI  - Large polypoid gastric leiomyoma with intermittent duodenal prolapse.
AB  - A case of large pedunculated gastric leiomyoma with intermittent prolapse into
      the duodenum, causing a somewhat confusing clinical picture is presented.
      Ultrasound-, CT- and barium studies clearly showed the origin and extent of the
      tumor. Sonography was the only imaging method that showed intermittent prolapse
      of the tumor during examination. Imaging studies did not allow prediction of the
      benign nature of the tumor.

PMID- 8253657
TI  - Parosteal osteosarcoma.
AB  - A case of parosteal osteosarcoma is reported. In spite of the pathognomonic plain
      radiographic signs of parosteal osteosarcoma, it is very uneasy to differentiate
      it from myositis ossificans circumscripta in the mature stage. CT and MRI defined
      the extent of the tumor into the soft tissue, the medullary and cortical invasion
      and gave more information about the composition of the lesion.

PMID- 8253658
TI  - Retropharyngeal liposarcoma.
AB  - We report a case of a large inhomogeneous tumor confined to the retropharyngeal
      space, visualised by CT and MRI, which proved to be a liposarcoma. Liposarcoma in
      the head and neck region is a very rare condition and a retropharyngeal location
      has only been described once previously.

PMID- 8253659
TI  - [Post-traumatic gas in the portal system in a child].

PMID- 8253660
TI  - Hepatic candidiasis: MR findings at 2-Teslas.

PMID- 8253661
TI  - [Selective embolization of cerebral arteriovenous malformations].

PMID- 8253662
TI  - [Key words and key images].

PMID- 8253663
TI  - Color sensing in the Archaea: a eukaryotic-like receptor coupled to a prokaryotic
      transducer.

PMID- 8253664
TI  - Identification of esg, a genetic locus involved in cell-cell signaling during
      Myxococcus xanthus development.
AB  - JD258, a Tn5 insertion mutant of Myxococcus xanthus, was shown to have major
      defects in three development-associated properties: expression of the
      developmentally regulated tps gene, spore formation, and production of
      multicellular fruiting bodies. The defects in tps gene expression and sporulation
      could be substantially corrected, at the phenotypic level, by mixing JD258 with
      wild-type cells (extracellular complementation). By this criterion, JD258
      appeared to be a new member of a group of conditional developmental mutants that
      were previously characterized and placed in four extracellular complementation
      groups (A to D) based on the ability of mutants in one group to stimulate
      development in mutants belonging to a different group (D. C. Hagen, A. P.
      Bretscher, and D. Kaiser, Dev. Biol. 64:284-296, 1978). Mutants from groups A, B,
      C, and D all displayed extracellular complementation activity when mixed with
      JD258. These results, and other aspects of the phenotype of JD258, indicate that
      this mutant defines a fifth extracellular complementation group, group E. The M.
      xanthus esg locus identified by the Tn5 insertion in JD258 was cloned in
      Escherichia coli and used for further genetic analysis of the locus. These
      studies indicated that the esg locus resides within a 2.5-kb region of the M.
      xanthus chromosome and that the locus contains at least two genetic
      complementation groups. Our results are consistent with a model in which the esg
      locus controls the production of a previously unrecognized extracellular signal
      that must be transmitted between cells for the completion of M. xanthus
      development.

PMID- 8253665
TI  - Determinants of the quantity of the stable SecY complex in the Escherichia coli
      cell.
AB  - While SecY in wild-type Escherichia coli cells is stable and is complexed with
      other proteins within the membrane, moderately overexpressed and presumably
      uncomplexed SecY was degraded with a half-life of 2 min. The fact that the amount
      of stable SecY is strictly regulated by the degradation of excess SecY was
      demonstrated by competitive entry of the SecY+ protein and a SecY-LacZ alpha
      fusion protein into the stable pool. Simultaneous overexpression of SecE led to
      complete stabilization of excess SecY. Overproduced SecD and SecF did not affect
      the stability of SecY, but plasmids carrying ORF12 located within the secD-secF
      operon partially stabilized this protein. In contrast, mutational reduction of
      the SecE content (but not the ORF12 content) led to the appearance of two
      populations of newly synthesized SecY molecules, one that was immediately
      degraded and one that was completely stable. Thus, the E. coli cell is equipped
      with a system that eliminates SecY unless it is complexed with SecE, a limiting
      partner of SecY. Our observations implied that in wild-type cells, SecY and SecE
      rapidly associate with each other and remain complexed.

PMID- 8253666
TI  - Isolation of the gene (miaE) encoding the hydroxylase involved in the synthesis
      of 2-methylthio-cis-ribozeatin in tRNA of Salmonella typhimurium and
      characterization of mutants.
AB  - The modified nucleoside 2-methylthio-N-6-isopentenyl adenosine (ms2i6A) is
      present at position 37 (3' of the anticodon) of tRNAs that read codons beginning
      with U except tRNA(I,V Ser) in Escherichia coli. Salmonella typhimurium 2
      methylthio-cis-ribozeatin (ms2io6A) is found in tRNA, probably in the
      corresponding species that have ms2i6A in E. coli. The gene (miaE) for the
      tRNA(ms2io6A)hydroxylase of S. typhimurium was isolated by complementation in E.
      coli. The miaE gene was localized close to the argI gene at min 99 of the S.
      typhimurium chromosomal map. Its DNA sequence and transcription pattern together
      with complementation studies revealed that the miaE gene is the second gene of a
      dicistronic operon. Southern blot analysis showed that the miaE gene is absent in
      E. coli, a finding consistent with the absence of the hydroxylated derivative of
      ms2i6A in this species. Mutants of S. typhimurium which have MudJ inserted in the
      miaE gene and which, consequently, are blocked in the ms2i6A hydroxylation
      reaction were isolated. Unexpectedly, such mutants cannot utilize the citric acid
      cycle intermediates malate, fumarate, and succinate as carbon sources.

PMID- 8253667
TI  - A 3.9-kb DNA region of Xanthomonas campestris pv. campestris that is necessary
      for lipopolysaccharide production encodes a set of enzymes involved in the
      synthesis of dTDP-rhamnose.
AB  - By mutational analysis it was found that a 3.9-kb SmaI-XhoII DNA fragment of
      Xanthomonas campestris pv. campestris is involved in lipopolysaccharide (LPS)
      biosynthesis. LPS samples isolated from different mutants carrying mutations in
      the 3.9-kb SmaI-XhoII DNA fragment exhibited banding patterns in silver-stained
      sodium dodecyl sulfate-polyacrylamide gels markedly different from that of the
      wild-type LPS. Moreover, comparison of the monosaccharide composition obtained by
      high-performance anion-exchange chromatography with pulsed amperometric detection
      of LPS purified from wild-type Xanthomonas campestris pv. campestris B100 and
      from mutants with mutations in the 3.9-kb SmaI-XhoII DNA fragment revealed a lack
      of rhamnose moieties in the mutant LPS. Sequence analysis of this DNA fragment
      revealed four open reading frames (ORFs), designated ORF302, ORF183, ORF295, and
      ORF351. The deduced amino acid sequences of these ORFs showed a high degree of
      homology to the deduced amino acid sequences of the rfbC, rfbD, rfbA, and rfbB
      genes of Salmonella typhimurium LT2, which have been shown to encode a set of
      enzymes responsible for conversion of glucose 1-phosphate to dTDP-rhamnose.

PMID- 8253668
TI  - Genetic definition of the substrate selectivity of outer membrane porin protein
      OprD of Pseudomonas aeruginosa.
AB  - Earlier studies proved that Pseudomonas aeruginosa OprD is a specific porin for
      basic amino acids and imipenem. It was also considered to function as a
      nonspecific porin that allowed the size-dependent uptake of monosaccharides and
      facilitation of the uptake of quinolone and other antibiotics. In the present
      study, we utilized P. aeruginosa strains with genetically defined levels of OprD
      to characterize the in vivo substrate selectivity of this porin. An oprD::omega
      interposon mutant was constructed by gene replacement utilizing an in vitro
      mutagenized cloned oprD gene. In addition, OprD was overexpressed from the lac
      promoter by cloning the oprD gene into the broad-host-range plasmid pUCP19. To
      test the substrate selectivity, strains were grown in minimal medium with
      limiting concentrations of the carbon sources glucose, gluconate, or pyruvate. In
      minimal medium with 0.5 mM gluconate, the growth rates of the parent strain H103
      and its oprD::omega mutant H729 were only 60 and 20%, respectively, of that of
      the OprD-overexpressing strain H103(pXH2). In contrast, no significant
      differences were observed in the growth rates of these three strains on glucose
      or pyruvate, indicating that OprD selectively facilitated the transport of
      gluconate. To determine the role of OprD in antibiotic uptake, nine strains
      representing different levels of OprD and OprF were used to determine the MICs of
      different antibiotics. The results clearly demonstrated that OprD could be
      utilized by imipenem and meropenem but that, even when substantially
      overexpressed, it could not be significantly utilized by other beta-lactams,
      quinolones, or aminoglycosides. In addition, competition experiments confirmed
      that imipenem had common binding sites with basic amino acids in the OprD
      channel, but not with gluconate or glucose.

PMID- 8253669
TI  - Evidence of two levels of control of P1 oriR and host oriC replication origins by
      DNA adenine methylation.
AB  - A mutant mini-P1 plasmid with increased copy number can be established in Dam-
      strains of Escherichia coli, where mini-P1 plasmid replication is normally
      blocked. Comparison of this plasmid and a plasmid driven by the host oriC
      replication origin showed that both origins are subject to control by methylation
      at two different levels. First, both origins appear to be subject to negative
      regulation acting at the level of hemimethylation. This probably involves the
      sequestration of the hemimethylated DNA produced by replication, as has been
      previously described for oriC. Second, both origins show a positive requirement
      for adenine methylation for efficient function in vivo. This conclusion is
      supported by the behavior of the P1 origin in an improved in vitro replication
      system. In vitro, where sequestration of hemimethylated DNA is not expected to
      occur, the hemimethylated P1 origin DNA was fully functional as a template.
      However, the activity of fully unmethylated DNA was severely restricted in
      comparison with that of either of the methylated forms. This in vitro uncoupling
      of the two effects of origin methylation suggests that two separate mechanisms
      are involved.

PMID- 8253670
TI  - Role of disulfide bonds in maintaining the structural integrity of the sheath of
      Leptothrix discophora SP-6.
AB  - Isolated sheaths of Leptothrix discophora SP-6 (ATCC 51168) were tested for
      susceptibility to degradation by a variety of chemical denaturants and lytic
      enzymes and found to be resistant to many reagents and enzyme treatments.
      However, disulfide bond-reducing agents such as dithiothreitol (DTT), beta
      mercaptoethanol, sodium cyanide, and sodium sulfite degraded the sheath,
      especially at elevated pH (pH 9) and temperature (50 degrees C). DTT and beta
      mercaptoethanol caused more rapid degradation of the sheath than cyanide or
      sulfite. Treatment of the sheath with 1 N NaOH resulted in rapid breakdown, while
      treatment with 1 N HCl resulted in slow but significant hydrolysis. Transmission
      electron microscopy showed that the 6.5-nm fibrils previously shown to be an
      integral structural element of the sheath fabric (D. Emerson and W. C. Ghiorse,
      J. Bacteriol. 175:7808-7818, 1993) were progressively dissociated into random
      masses during DTT-induced degradation. Quantitation of disulfide bonds with DTT
      showed that the sheaths contained approximately 2.2 mumol of disulfides per mg of
      sheath protein. Reaction with 5,5'-dithio-bis-(2-nitrobenzoic acid) showed that
      sheaths also contained approximately 0.8 mumol of free sulfhydryls per mg of
      protein. A sulfhydryl-specific fluorescent probe (fluorescein 5-maleimide) showed
      that the free sulfhydryls in sheathed cell filaments were evenly distributed
      throughout the sheath. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      autoradiography of [14C]iodoacetamide-labeled sheaths and DTT-dissociated sheath
      fibril suspensions showed that the majority of 14C-labeled sulfhydryls in the
      sheaths did not enter the gel. However, low-molecular-mass silver-staining bands
      (14 to 45 kDa) did appear in the gels after iodoacetic acid or iodoacetamide
      alkylation of the dissociated fibrils. These bands did not stain with Coomassie
      blue. Their migration in gels was slightly affected by digestion with pronase.
      The fibrils contained 20 to 25% protein. These results confirm that the sheath
      fibrils consist of high molecular-weight heteropolysaccharide-protein complexes.
      We hypothesize that proteins in the fibril complexes provide interfibril cross
      linking to maintain the structural integrity of the sheath.

PMID- 8253671
TI  - Evidence for autoregulation of camR, which encodes a repressor for the cytochrome
      P-450cam hydroxylase operon on the Pseudomonas putida CAM plasmid.
AB  - The regulatory gene camR on the CAM plasmid of Pseudomonas putida (ATCC 17453)
      negatively controls expression of the cytochrome P-450cam hydroxylase operon
      (camDCAB) for the camphor degradation pathway and is oriented in a direction
      opposite to that of the camDCAB operon. In this study, we examined expression of
      the camR gene by monitoring the beta-galactosidase activity of camR-lacZ
      translational fusions in P. putida camR and camR+ strains. We found that the camR
      gene was autogenously regulated by its own product, CamR. To search for an
      operator site of the camR gene, a cam repressor (CamR)-overproducing plasmid,
      pHAOV1, was constructed by placing the camR gene under the control of a pL
      promoter. The translational initiation codon of CamR was changed by site-directed
      mutagenesis from GTG to ATG to improve translation efficiency. Judging from
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the CamR
      protein was expressed up to about 10% of the soluble protein of CamR
      overproducing Escherichia coli JM83/pHAOV1 cells. Results of DNase I footprinting
      assays using the cell lysate indicated that the CamR repressor covered a single
      region between the camR gene and the camDCAB operon. Our findings also suggest
      that the camR gene autogenously regulates its own expression by binding of the
      gene product, CamR, to the operator, which also serves as an operator of the
      camDCAB operon.

PMID- 8253672
TI  - Excess intracellular concentration of the pSC101 RepA protein interferes with
      both plasmid DNA replication and partitioning.
AB  - RepA, a plasmid-encoded gene product required for pSC101 replication in
      Escherichia coli, is shown here to inhibit the replication of pSC101 in vivo when
      overproduced 4- to 20-fold in trans. Unlike plasmids whose replication is
      prevented by mutations in the repA gene, plasmids prevented from replicating by
      overproduction of the RepA protein were lost rapidly from the cell population
      instead of being partitioned evenly between daughter cells. Removal of the
      partition (par) locus increased the inhibitory effect of excess RepA on
      replication, while host and plasmid mutations that compensate for the absence of
      par, or overproduction of the E. coli DnaA protein, diminished it. A repA
      mutation (repA46) that elevates pSC101 copy number almost entirely eliminated the
      inhibitory effect of RepA at high concentration and stimulated replication when
      the protein was moderately overproduced. As the RepA protein can exist in both
      monomer and dimer forms, we suggest that overproduction promotes RepA
      dimerization, reducing the formation of replication initiation complexes that
      require the RepA monomer and DnaA; we propose that the repA46 mutation alters the
      ability of the mutant protein to dimerize. Our discovery that an elevated
      intracellular concentration of RepA specifically impedes plasmid partitioning
      implies that the RepA-containing complexes initiating pSC101 DNA replication
      participate also in the distribution of plasmids at cell division.

PMID- 8253673
TI  - Membrane-associated nuclease activities in mycoplasmas.
AB  - Membrane-associated nucleases of various mycoplasmal species were investigated by
      using two nuclease assays. A lambda DNA assay was developed to measure nuclease
      activity associated with whole-cell suspensions, activity released from intact
      cells, and activity associated with detergent-disrupted cells. In most species,
      nuclease activities were entirely membrane associated, and disruption by a
      detergent had a stimulatory effect on these activities. All mycoplasmal species
      contained nuclease activity, but Mycoplasma capricolum was unusual because its
      activity was dependent upon magnesium and was inhibited by calcium. We developed
      a sodium dodecyl sulfate-polyacrylamide gel electrophoresis system that produced
      reproducible nuclease patterns, and this system was used to determine the
      apparent molecular weights of the nuclease proteins. An examination of 20
      mycoplasmal species failed to identify common bands in their nuclease patterns.
      An examination of 11 Mycoplasma pulmonis strains, however, indicated that
      nuclease patterns on polyacrylamide gels may provide a means for categorizing
      strains within a species. Our results suggest that nucleases are important
      constituents of mycoplasmal membranes and may be involved in the acquisition of
      host nucleic acids required for growth.

PMID- 8253674
TI  - The Cox protein is a modulator of directionality in bacteriophage P2 site
      specific recombination.
AB  - The P2 Cox protein is known to repress the Pc promoter, which controls the
      expression of the P2 immunity repressor C. It has also been shown that Cox can
      activate the late promoter PLL of the unrelated phage P4. By this process, a P2
      phage infecting a P4 lysogen is capable of inducing replication of the P4 genome,
      an example of viral transactivation. In this report, we present evidence that Cox
      is also directly involved in both prophage excision and phage integration. While
      purified Cox, in addition to P2 Int and Escherichia coli integration host factor,
      was required for attR x attL (excisive) recombination in vitro, it was inhibitory
      to attP x attB (integrative) recombination. The same amounts of Int and
      integration host factor which mediated optimal excisive recombination in vitro
      also mediated optimal integrative recombination. We quantified and compared the
      relative efficiencies of attB, attR, and attL in recombination with attP and
      discuss the functional implications of the results. DNase I protection
      experiments revealed an extended 70-bp Cox-protected region on the right arm of
      attP, centered at about +60 bp from the center of the core sequence. Gel shift
      assays suggest that there are two Cox binding sites within this region. Together,
      these data support the theory that in vivo, P2 can exert control over the
      direction of recombination by either expressing Int alone or Int and Cox
      together.

PMID- 8253675
TI  - The ancestry of insertion sequences common to Escherichia coli and Salmonella
      typhimurium.
AB  - Despite very restricted gene exchange between Escherichia coli and Salmonella
      typhimurium, both species harbor several of the same classes of insertion
      sequences. To determine whether the present-day distribution of these
      transposable elements is due to common ancestry or to horizontal transfer, we
      determined the sequences of IS1 and IS200 from natural isolates of S. typhimurium
      and E. coli. One strain of S. typhimurium harbored an IS1 element identical to
      that originally recovered from E. coli, suggesting that the element was recently
      transferred between these two species. The level of sequence divergence between
      copies of IS200 from E. coli and S. typhimurium ranged from 9.5 to 10.7%,
      indicating that IS200, unlike IS1, has not been repeatedly transferred between
      these enteric species since E. coli and S. typhimurium diverged from a common
      ancestor. Levels of variability in IS1 and IS200 for strains of E. coli and S.
      typhimurium show that each class of insertion sequence has a characteristic
      pattern of transposition within and among host genomes.

PMID- 8253676
TI  - Presence of one linear and one circular chromosome in the Agrobacterium
      tumefaciens C58 genome.
AB  - Analysis of the entire Agrobacterium tumefaciens C58 genome by pulsed-field gel
      electrophoresis (PFGE) reveals four replicons: two large molecules of 3,000 and
      2,100 kb, the 450-kb cryptic plasmid, and the 200-kb Ti plasmid. Digestion by
      PacI or SwaI generated 12 or 14 fragments, respectively. The two megabase-sized
      replicons, used as probes, hybridize with different restriction fragments,
      showing that these replicons are two independent genetic entities. A 16S rRNA
      probe and genes encoding functions essential to the metabolism of the organism
      were found to hybridize with both replicons, suggesting their chromosomal nature.
      In PFGE, megabase-sized circular DNA does not enter the gel. The 2.1-Mb
      chromosome always generated an intense band, while the 3-Mb band was barely
      visible. After linearization of the DNA by X-irradiation, the intensity of the 3
      Mb band increased while that of the 2.1-Mb remained constant. This suggests that
      the 3-Mb chromosome is circular and that the 2.1-Mb chromosome is linear. To
      confirm this hypothesis, genomic DNA, trapped in an agarose plug, was first
      submitted to PFGE to remove any linear DNA present. The plug was then recovered,
      and the remaining DNA was digested with either PacI or SwaI and then separated by
      PFGE. The fragments corresponding to the small chromosome were found to be
      absent, while those corresponding to the circular replicon remained, further
      proof of the linear nature of the 2.1-Mb chromosome.

PMID- 8253677
TI  - The chromosomal virulence gene, chvE, of Agrobacterium tumefaciens is regulated
      by a LysR family member.
AB  - Certain plant phenolic compounds and monosaccharides induce the transcription of
      virulence (vir) genes of Agrobacterium tumefaciens through the VirA-VirG two
      component regulatory system. The product of the chromosomal virulence gene chvE
      is homologous to galactose-binding protein of Escherichia coli and is required
      for vir gene induction by sugars. Adjacent to, but divergent in transcription
      from, chvE is an open reading frame, now termed gbpR (galactose-binding protein
      regulator), that is homologous to the LysR family of transcriptional regulators.
      chvE::lacZ expression was induced by L-arabinose, D-galactose, and D-fucose when
      gbpR was present. In the absence of inducer, GbpR repressed chvE::lacZ
      expression. In addition, GbpR negatively regulated its own expression.

PMID- 8253678
TI  - A cytotoxic early gene of Bacillus subtilis bacteriophage SPO1.
AB  - Some of the early genes of Bacillus subtilis bacteriophage SPO1 were hypothesized
      to function in the shutoff of host biosyntheses. Two of these genes, e3 and e22,
      were cloned and sequenced. E22 showed no similarity to any known protein, while
      E3, a highly acidic protein, showed significant similarity only to other
      similarly acidic proteins. Each gene was immediately downstream of a very active
      early promoter. Each was expressed actively during the first few minutes of
      infection and was then rapidly shut off and its RNA rapidly degraded. An e3
      nonsense mutation severely retarded the degradation of e3 RNA. Expression of a
      plasmid-borne e3 gene, in either B. subtilis or Escherichia coli, resulted in the
      inhibition of host DNA, RNA, and protein syntheses and prevented colony
      formation. However, the e3 nonsense mutation caused no measurable decrease in
      either burst size or host shutoff during infection and, in fact, caused an
      increased burst size at high multiplicities of infection. We suggest that e3 is
      one of several genes involved in host shutoff, that its function is dispensable
      both for host shutoff and for phage multiplication, and that its shutoff function
      is not entirely specific to host activities.

PMID- 8253679
TI  - Complex transcriptional control of the sigma s-dependent stationary-phase-induced
      and osmotically regulated osmY (csi-5) gene suggests novel roles for Lrp, cyclic
      AMP (cAMP) receptor protein-cAMP complex, and integration host factor in the
      stationary-phase response of Escherichia coli.
AB  - osmY (csi-5) is a representative of a large group of sigma s-dependent genes in
      Escherichia coli that exhibit both stationary-phase induction and osmotic
      regulation. A chromosomal transcriptional lacZ fusion (csi-5::lacZ) was used to
      study the regulation of osmY. We show here that in addition to sigma s, the
      global regulators Lrp, cyclic AMP (cAMP) receptor protein-cAMP complex (cAMP
      CRP), and integration host factor (IHF) are involved in the control of osmY. All
      three regulators negatively modulate the expression of osmY, and they act
      independently from sigma s. Stationary-phase induction of osmY in minimal medium
      can be explained by stimulation by sigma s combined with a relief of Lrp
      repression. Stationary-phase induction of osmY in rich medium is mediated by the
      combined action of sigma s, Lrp, cAMP-CRP, and IHF, with the latter three
      proteins acting as transition state regulators. The transcriptional start site of
      osmY was determined and revealed an mRNA with an unusual long nontranslated
      leader of 244 nucleotides. The regulatory region is characterized by a sigma 70
      like -10 promoter region and contains potential binding sites for Lrp, CRP, and
      IHF. Whereas sigma s, Lrp, CRP, and IHF are clearly involved in stationary-phase
      induction, none of these regulators is essential for osmotic regulation of osmY.

PMID- 8253681
TI  - Stress-induced activation of the sigma B transcription factor of Bacillus
      subtilis.
AB  - The alternative transcription factor sigma B of Bacillus subtilis is activated
      during the stationary growth phase by a regulatory network responsive to
      stationary-phase signals. On the basis of the results reported here, we propose
      that sigma B controls a general stress regulon that is induced when cells
      encounter a variety of growth-limiting conditions. Expression of genes controlled
      by sigma B, including the ctc gene and the sigB operon that codes for sigma B and
      its associated regulatory proteins, was dramatically induced in both the
      exponential and stationary phases by environmental challenges known to elicit a
      general stress response. After cells were subjected to salt stress, the increased
      expression of lacZ transcriptional fusions to the ctc and sigB genes was entirely
      dependent on sigma B, and primer extension experiments confirmed that the sigma B
      dependent transcriptional start site was used during salt induction of sigB
      operon expression. Western blotting (immunoblotting) experiments measuring the
      levels of sigma B protein indicated that ethanol addition and heat stress also
      induced sigma B activity during logarithmic growth. Salt and ethanol induction
      during logarithmic growth required RsbV, the positive regulator of sigma B
      activity that is normally necessary for activity in stationary-phase cells.
      However, heat induction of sigma B activity was largely independent of RsbV,
      indicating that there are two distinct pathways by which these environmental
      signals are conveyed to the transcriptional apparatus.

PMID- 8253680
TI  - A survey of the Mycoplasma genitalium genome by using random sequencing.
AB  - A total of 508 random clones from five Mycoplasma genitalium genomic libraries
      were partially sequenced and analyzed. This resulted in the identification of 291
      unique contigs. Sequence information from these clones (100,993 nucleotides),
      representing approximately 17% of this pathogen's genome, was analyzed by
      comparison to the DNA and protein sequence data bases. The frequency with which
      clones could be identified, by virtue of possessing homology to another data base
      entry, was 46%. Sequence analysis indicated the following. (i) The M. genitalium
      genome contains many genes involved in various metabolic processes. (ii)
      Repetitive DNA may comprise as much as 4% of this genome. (iii) The MgPa adhesin
      gene may be the result of horizontal transfer from an unknown origin. (iv) Not
      all dinucleotide pairs are present in this genome at the expected frequency. (v)
      This genome potentially encodes approximately 390 proteins and makes very
      efficient use of its limited amount of DNA. In addition, this study allowed us to
      estimate the number of genes involved with various cellular functions.

PMID- 8253682
TI  - Sequence and genetic characterization of etrA, an fnr analog that regulates
      anaerobic respiration in Shewanella putrefaciens MR-1.
AB  - An electron transport regulatory gene, etrA, has been isolated and characterized
      from the obligate respiratory bacterium Shewanella putrefaciens MR-1. The deduced
      amino acid sequence of etrA (EtrA) shows a high degree of identity to both the
      Fnr of Escherichia coli (73.6%) and the analogous protein (ANR) of Pseudomonas
      aeruginosa (50.8%). The four active cysteine residues of Fnr are conserved in
      EtrA, and the amino acid sequence of the DNA-binding domains of the two proteins
      are identical. Further, S. putrefaciens etrA is able to complement an fnr mutant
      of E. coli. In contrast to fnr, there is no recognizable Fnr box upstream of the
      etrA sequence. Gene replacement etrA mutants of MR-1 were deficient in growth on
      nitrite, thiosulfate, sulfite, trimethylamine-N-oxide, dimethyl sulfoxide,
      Fe(III), and fumarate, suggesting that EtrA is involved in the regulation of the
      corresponding reductase genes. However, the mutants were all positive for
      reduction of and growth on nitrate and Mn(IV), indicating that EtrA is not
      involved in the regulation of these two systems. Southern blots of S.
      putrefaciens DNA with use of etrA as a probe revealed the expected etrA bands and
      a second set of hybridization signals whose genetic and functional properties
      remain to be determined.

PMID- 8253683
TI  - A flavoprotein functional as NADH oxidase from Amphibacillus xylanus Ep01:
      purification and characterization of the enzyme and structural analysis of its
      gene.
AB  - Amphibacillus xylanus Ep01, a facultative anaerobe we recently isolated, shows
      rapid aerobic growth even though it lacks a respiratory pathway. Thus, the
      oxidative consumption of NADH, produced during glycolysis and pyruvate oxidation,
      should be especially important for maintenance of intracellular redox balance in
      this bacterium. We purified a flavoprotein functional as NADH oxidase from
      aerobically growing A. xylanus Ep01. The A. xylanus enzyme is a homotetramer
      composed of a subunit (M(r) 56,000) containing 1 mol of flavin adenine
      dinucleotide. This enzyme catalyzes the reduction of oxygen to hydrogen peroxide
      with beta-NADH as the preferred electron donor and exhibits no activity with
      NADPH. The flavoprotein gene of A. xylanus Ep01 was cloned by using a specific
      antibody. The amino acid sequence of 509 residues, deduced from the nucleotide
      sequence, showed 51.2 and 72.5% identities to the amino acid sequences of alkyl
      hydroperoxide reductase from Salmonella typhimurium and NADH dehydrogenase from
      alkalophilic Bacillus sp. strain YN-1, respectively. Bacillus spp. have a
      respiratory chain and grow well under aerobic conditions. In contrast,
      Amphibacillus spp., having no respiratory chain, grow equally well under both
      aerobic and anaerobic conditions, which distinguishes these two genera.
      Salmonella spp., which are gram-negative bacteria, are taxonomically distant from
      gram-positive bacteria such as Bacillus spp. and Amphibacillus spp. The above
      findings, however, suggest that the flavoprotein functional as NADH oxidase, the
      alkyl hydroperoxide reductase, and the NADH dehydrogenase diverged recently, with
      only small changes leading to their functional differences.

PMID- 8253684
TI  - HrpI of Erwinia amylovora functions in secretion of harpin and is a member of a
      new protein family.
AB  - HrpI, a 78-kDa protein, functions in the secretion of harpin, a proteinaceous
      elicitor of the hypersensitive response from Erwinia amylovora. The predicted
      amino acid sequence of HrpI is remarkably similar to that of LcrD of Yersinia
      species, the first member of a recently described protein family. Other proteins
      of the family are MixA from Shigella flexneri, InvA from Salmonella typhimurium,
      FlhA from Caulobacter crescentus, HrpI from Pseudomonas syringae pv. syringae,
      HrpO from Pseudomonas solanacearum, and HrpC2 from Xanthomonas campestris pv.
      vesicatoria. Cells of E. amylovora containing mutated hrpI genes or cells of
      Escherichia coli containing the cloned hrp gene cluster with mutated hrpI produce
      but do not export harpin. When similar cells with functional hrpI genes were
      grown at 25 degrees C, but not at 37 degrees C, harpin was exported to the
      culture supernatant. Direct evidence that HrpI is involved in the secretion of a
      virulence protein has been offered. Two other loci of the hrp gene cluster are
      involved in the regulation of harpin, and four other loci also are involved in
      the secretion of harpin. Since harpin and other proteins likely to be secreted by
      the LcrD family of proteins lack typical signal peptides, their secretion
      mechanism is distinct from the general protein export pathway.

PMID- 8253685
TI  - Synthesis of the stationary-phase sigma factor sigma s is positively regulated by
      ppGpp.
AB  - Strains of Escherichia coli which lack detectable guanosine 3',5'
      bispyrophosphate (ppGpp) display a pleiotropic phenotype that in some respects
      resembles that of rpoS (katF) mutants. This led us to examine whether ppGpp is a
      positive regulator of sigma s synthesis. sigma s is a stationary-phase-specific
      sigma factor that is encoded by the rpoS gene. We found that a ppGpp-deficient
      strain is defective in sigma s synthesis as cells enter stationary phase in a
      rich medium, as judged by immunoblots. Under more-defined conditions we found
      that the stimulation of sigma s synthesis following glucose, phosphate, or amino
      acid starvation of wild-type strains is greatly reduced in a strain lacking
      ppGpp. The failure of ppGpp-deficient strains to synthesize sigma s in response
      to these starvation regimens could indicate a general defect in gene expression
      rather than a specific dependence of rpoS expression on ppGpp. We therefore
      tested the effect of artificially elevated ppGpp levels on sigma s synthesis
      either with mutations that impair ppGpp decay or by gratuitously inducing ppGpp
      synthesis with a Ptac::relA fusion. In both instances, we observed enhanced sigma
      s synthesis. Apparently, ppGpp can activate sigma s synthesis under conditions of
      nutrient sufficiency as well as during entry into stationary phase. This finding
      suggests that changes in ppGpp levels function both as a signal of imminent
      stationary phase and as a signal of perturbations in steady-state growth.

PMID- 8253686
TI  - Expression and purification of the cynR regulatory gene product: CynR is a DNA
      binding protein.
AB  - The CynR protein, a member of the LysR family, positively regulates the
      Escherichia coli cyn operon and negatively autoregulates its own transcription.
      By S1 mapping analysis, the in vivo cynR transcription start site was located 63
      bp upstream of the cynTSX operon transcription start site. Topologically, the
      cynR and cynTSX promoters overlap and direct transcription in opposite
      directions. The CynR translation initiation codon was identified by
      oligonucleotide-directed mutagenesis, and the CynR coding sequence was cloned
      under the control of a T7 phage promoter. The CynR protein was stably expressed
      at a high level with a T7 RNA polymerase-T7 phage promoter system. Purification
      by ion-exchange chromatography, affinity chromatography, and ammonium sulfate
      fractionation yielded pure CynR protein. Gel shift assays confirmed that CynR is
      a DNA-binding protein like the other members of the LysR family. The CynR
      regulatory protein binds specifically to a 136-bp DNA fragment encompassing both
      the cynR and the cynTSX promoters.

PMID- 8253687
TI  - A species-specific periplasmic flagellar protein of Serpulina (Treponema)
      hyodysenteriae.
AB  - We have previously reported that a 46-kDa protein present in an outer membrane
      protein preparation seemed to be a species-specific antigen of Serpulina
      hyodysenteriae (Z. S. Li, N. S. Jensen, M. Belanger, M.-C. L'Esperance, and M.
      Jacques, J. Clin. Microbiol. 30:2941-2947, 1992). The objective of this study was
      to further characterize this antigen. A Western blot (immunoblot) analysis and
      immunogold labeling with a monospecific antiserum against this protein confirmed
      that the protein was present in all S. hyodysenteriae reference strains but not
      in the nonpathogenic organism Serpulina innocens. The immunogold labeling results
      also indicated that the protein was associated with the periplasmic flagella of
      S. hyodysenteriae. N-terminal amino acid sequencing confirmed that the protein
      was in fact a periplasmic flagellar sheath protein. The molecular mass of this
      protein, first estimated to be 46 kDa by Western blotting, was determined to be
      44 kDa when the protein was evaluated more precisely by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and the protein was glycosylated, as
      determined by glycoprotein staining and also by N-glycosidase F treatment. Five
      other periplasmic flagellar proteins of S. hyodysenteriae, which may have been
      the core proteins and had molecular masses of 39, 35, 32, 30, and 29 kDa, were
      antigenically related and cross-reacted with the periplasmic flagellar proteins
      of S. innocens. Finally, serum from a pig experimentally infected with S.
      hyodysenteriae recognized the 44-kDa periplasmic flagellar sheath protein. Our
      results suggest that the 44-kDa periplasmic flagellar sheath protein of S.
      hyodysenteriae is a species-specific glycoprotein antigen.

PMID- 8253688
TI  - Nitrate as a preferred electron sink for the acetogen Clostridium thermoaceticum.
AB  - Nitrate enhanced the vanillin- and vanillate-dependent growth of Clostridium
      thermoaceticum. Under nitrate-enriched conditions, these aromatic substrates were
      subject to O demethylation. However, acetate, the normal product obtained from O
      demethylation, was not detected. Acetate was also not detected when methanol and
      CO cultures were supplemented with nitrate; glucose cultures likewise produced
      approximately one-third less acetate when enriched with nitrate. Reductant
      derived from the oxidation of these substrates was recovered in nitrite and
      ammonia. With an ammonia-limited medium employed to evaluate N turnover, the
      following stoichiometry was observed concomitantly with the consumption of 2.0 mM
      O-methyl groups (the recovery of nitrate-derived N approximated 89%): 3.9 mM NO3(
      )-->2.8 mM NO2- +0.7 mM NH3. The results demonstrated that (i) nitrate was
      preferentially used as an electron sink under conditions that were otherwise
      acetogenic, (ii) nitrate dissimilation was energy conserving and growth
      supportive, and (iii) nitrate-coupled utilization of O-methyl groups conserved
      more energy than acetogenic O demethylation.

PMID- 8253689
TI  - Listeria monocytogenes phosphatidylinositol (PI)-specific phospholipase C has low
      activity on glycosyl-PI-anchored proteins.
AB  - The ability of the phosphatidylinositol-specific phospholipase C (PI-PLC) from
      Listeria monocytogenes to hydrolyze glycosyl phosphatidylinositol (GPI)-anchored
      membrane proteins was compared with the ability of the PI-PLC from Bacillus
      thuringiensis to hydrolyze such proteins. The L. monocytogenes enzyme produced no
      detectable release of acetylcholinesterase from bovine, sheep, and human
      erythrocytes. The cleavage of the GPI anchors of alkaline phosphatase from rat
      and rabbit kidney slices was less than 10% of the cleavage seen with the PI-PLC
      from B. thuringiensis. Activity for release of Fc gamma receptor IIIB (CD16) on
      human granulocytes was also low. Variations in pH and salt concentration had
      little effect on the release of GPI-anchored proteins. Our data show that L.
      monocytogenes PI-PLC has low activity on GPI-anchored proteins.

PMID- 8253690
TI  - Cloning, sequencing, expression, and complementation analysis of the Escherichia
      coli K1 kps region 1 gene, kpsE, and identification of an upstream open reading
      frame encoding a protein with homology to GutQ.
AB  - The kps locus for polysialic acid capsule expression in Escherichia coli K1 is
      composed of a central group of biosynthetic neu genes, designated region 2,
      flanked on either side by region 1 or region 3 kps genes with poorly defined
      functions. Chromosomal mutagenesis with MudJ and subsequent complementation
      analysis, maxicell and in vitro protein expression studies, and nucleotide
      sequencing identified the region 1 gene, kpsE, which encodes a 39-kDa
      polypeptide. Polarity of the kpsE::lacZ mutation suggests an operonic structure
      for region 1. KpsE is homologous to putative polysaccharide-translocation
      components previously identified in Haemophilus influenzae type b and Neisseria
      meningitidis group B. An open reading frame upstream of kpsE encodes a 35-kDa
      polypeptide with homology to GutQ, a putative ATP-binding protein of unknown
      function encoded by gutQ of the glucitol utilization operon. Whether expression
      of the gutQ homolog as the potential first gene of region 1 is required for
      polysialic acid synthesis or localization is presently unknown.

PMID- 8253691
TI  - Characterization of the rho genes of Neisseria gonorrhoeae and Salmonella
      typhimurium.
AB  - We have cloned and sequenced the genomic regions encompassing the rho genes of
      Neisseria gonorrhoeae and Salmonella typhimurium. Rho factor of S. typhimurium
      has only three amino acid differences with respect to the Escherichia coli
      homolog. Northern (RNA) blots and primer extension experiments were used to
      characterize the N. gonorrhoeae rho transcript and to identify the transcription
      initiation and termination elements of this cistron. The function of the Rho
      factor of N. gonorrhoeae was investigated by complementation assays of rho
      mutants of E. coli and S. typhimurium and by in vivo transcription assays in
      polar mutants of S. typhimurium.

PMID- 8253692
TI  - Regulation of the catechol 1,2-dioxygenase- and phenol monooxygenase-encoding
      pheBA operon in Pseudomonas putida PaW85.
AB  - In Pseudomonas putida PaW85, the ortho-cleavage pathway is used for catechol
      degradation. The 11.4-kb XhoI fragment cloned from phenol degradation plasmid
      pEST1226 into pKT240 (recombinant plasmid pAT1140) contains the inducible pheBA
      operon that encodes catechol 1,2-dioxygenase (gene pheB) and phenol monooxygenase
      (gene pheA), the first two enzymes for the phenol degradation pathway. The
      promoter of the pheBA operon is mapped 1.5 kb upstream of the pheB gene. The
      plasmid pAT1140, when introduced into P. putida PaW85, enables the bacteria to
      use the hybrid plasmid-chromosome-encoded pathway for phenol degradation. The
      synthesis of the plasmid-encoded phenol monooxygenase and catechol 1,2
      dioxygenase is induced by cis,cis-muconate. The expression studies of the
      deletion subclones derived from pAT1140 revealed that the transcription of the
      pheBA operon is positively controlled by a regulatory protein that is
      chromosomally encoded in P. putida. cis,cis-Muconate in cooperation with positive
      transcription factor CatR activates the transcription of the chromosomal ortho
      pathway genes catA and catBC in P. putida (R. K. Rothmel, T. L. Aldrich, J. E.
      Houghton, W. M. Coco, L. N. Ornston, and A. M. Chakrabarty, J. Bacteriol. 172:922
      931, 1990). The inability to express the pheBA operon in a P. putida CatR-
      background and activation of transcription of the pheBA operon in Escherichia
      coli in the presence of the catR-expressing plasmid demonstrated that the
      transcription of the pheBA operon in P. putida PaW85 carrying pEST1226 is
      controlled by the chromosomally encoded CatR.

PMID- 8253694
TI  - Identification of a putative Bacillus subtilis rho gene.

PMID- 8253693
TI  - A hydroxylase-like gene product contributes to synthesis of a polyketide spore
      pigment in Streptomyces halstedii.
AB  - A gene, schC, adjacent to the sch gene cluster encoding the biosynthesis of a
      polyketide spore pigment in Streptomyces halstedii was sequenced. Its deduced
      product resembled flavin adenine nucleotide-containing hydroxylases involved in
      the biosynthesis of polycyclic aromatic polyketide antibiotics and in catabolic
      pathways of aromatic compounds. When schC was disrupted, the normally green
      spores of S. halstedii became lilac. An schC-like gene was located in an
      equivalent position next to a large gene cluster (whiE) known to determine spore
      pigment in Streptomyces coelicolor A3(2).

PMID- 8253695
TI  - Psychiatry 2013.

PMID- 8253696
TI  - Seizures associated with antidepressants: a review.
AB  - BACKGROUND: Seizures are uncommon, but serious, adverse effects of antidepressant
      drugs. A better understanding of drug-related seizure risk, its predictors, and
      its neurophysiologic basis might help clinicians avoid this adverse event. A
      better understanding of the factors involved in the determination of seizure risk
      would be helpful for interpretation of seizure rates reported. METHOD: The
      authors review case reports, series of cases, and information from clinical
      trials of antidepressants to determine antidepressant-related seizure risk.
      Predisposing factors are identified. Effects of dose, blood levels, and duration
      of treatment on seizure risk are examined. Electrophysiologic and in vitro models
      of drug-related seizure induction are discussed. RESULTS: A significant
      proportion of drug-related seizures occurs in individuals with an identifiable
      predisposition, such as previous seizures, sedative or alcohol withdrawal, and
      multiple concomitant medications. Seizure risk for most antidepressants increases
      with dose (or blood level), and comparisons between drugs should consider seizure
      rates at the effective dose (or blood level) for each drug. For imipramine, the
      most frequently studied tricyclic, the literature indicates a seizure rate
      between 0.3% and 0.6% at effective doses. In unselected patients and at higher
      doses, these rates may be higher. Fluoxetine, sertraline, fluvoxamine, trazodone,
      nomifensine, and the monoamine oxidase inhibitors have a lower seizure risk.
      Estimates for recently marketed antidepressants with intermediate seizure risk
      are complicated by the fact that effective doses and blood levels are not well
      established. CONCLUSION: Assessment of seizure risk in individuals involves
      consideration of predisposing factors, the antidepressant selected, and the
      bioavailability of the drug. Future studies of seizure risk would benefit from
      the use of specified criteria for determination of probable seizure events, a
      priori definition of predisposing exclusions, samples sufficiently large to
      provide adequate power, blood level monitoring, and inclusion of duration of drug
      treatment in the calculation of risk.

PMID- 8253697
TI  - The effect of valproate on bipolar spectrum temperamental disorders.
AB  - BACKGROUND: Cyclothymic or hyperthymic temperaments may belong to a bipolar
      spectrum of disorders. Patients with such temperaments, especially if there is a
      family history of bipolar disorder or an exacerbation of these conditions when
      exposed to tricyclic antidepressants, should be conceptualized as possessing
      variants of bipolar disorder. This conceptualization suggests that standard
      psychopharmacologic regimens used in treating bipolar disorder may be useful. In
      this report I examine the potential usefulness of valproate in treating
      temperamental variants of bipolar disorder. METHOD: The author reports his
      experience of treating patients with bipolar temperamental disorders in an
      Outpatient Affective Disorder Specialty Clinic. Three representative case reports
      are offered, as well as a discussion of the general issues in the diagnosis and
      treatment of these patients. RESULTS: In these cases, valproate not only treated
      the acute symptomatology that caused these patients to seek treatment, but also
      led to an amelioration of noxious life-long temperamental traits. These findings
      strengthen other research findings that suggest a link between bipolar disorder
      and limbic dysfunction and add to the validation of the concept of bipolar
      temperamental disorders. CONCLUSION: Valproate may be a safe and effective
      treatment for patients with cyclothymic and hyperthymic temperaments.

PMID- 8253698
TI  - Valproate oral loading in the treatment of acute mania.
AB  - BACKGROUND: Evidence from earlier studies suggests that the antimanic activity of
      valproate becomes most pronounced within 1 to 4 days of achieving serum
      concentrations of 50 mg/L or greater. We conducted a prospective study to assess
      the onset of antimanic activity of oral loading dosages of valproate administered
      to achieve serum concentrations above 50 mg/L within 24 hours. METHOD: Nineteen
      patients with bipolar disorder, manic phase, received divalproex sodium 20
      mg/kg/day in divided dosages for 5 days, without other psychotropic agents except
      lorazepam up to 4 mg/day. Serum valproate concentrations were measured after 1
      and 4 days of treatment. Improvement was measured daily by a blind rater using
      the Young Mania Rating Scale (MRS). RESULTS: Serum valproate concentrations
      greater than 50 mg/L were reached in all 15 patients completing the study. Ten
      (53%) of the 19 patients who received at least one complete loading dose
      displayed a significant (greater than 50%) reduction in MRS scores by study
      termination. These responders displayed the greatest percent change in MRS scores
      over the first 3 days of treatment. Side effects were minimal. CONCLUSION:
      Valproate can be safely administered by oral loading and may produce rapid onset
      of antimanic response in some patients.

PMID- 8253699
TI  - Analyses of suicidality in double-blind, placebo-controlled trials of
      pharmacotherapy for weight reduction.
AB  - BACKGROUND: The obese who seek therapy may also have depression and thus a risk
      for suicidality (suicidal acts and ideation). For this reason and because of
      interest in the potential impact of a medication with antidepressant properties
      on suicidality in a population without a primary diagnosis of depression, we
      performed a comprehensive analysis of suicidality data from clinical trials in
      patients seeking weight-reduction therapy. METHOD: Suicidality data from 11
      double-blind controlled trials in the United States Investigational New Drug
      fluoxetine obesity clinical trial data base (3819 randomized outpatients) were
      reviewed. Trials lasted 6 to 60 weeks (continuous and intermittent therapy
      designs). They included obese men and women (median body mass index, 35.0 kg/m2).
      Trials excluded patients treated with antidepressants. Incidence of suicidality
      was analyzed by the incidence difference method. RESULTS: No fatal suicidal acts
      occurred. One suicide attempt was reported in a patient receiving placebo after
      prior fluoxetine therapy (intermittent therapy trial). The overall incidence of
      suicidal ideation among fluoxetine-treated and placebo-treated patients in the
      obesity clinical trials was 0.24%. The difference in incidence of emergent
      suicidal ideation in fluoxetine-treated (0.23%) and placebo-treated patients
      (0.27%) was not statistically significant. CONCLUSION: Based on these analyses of
      controlled clinical trials, suicidality occurs but has a low incidence rate in
      the obese who seek pharmacologic weight-reduction therapy. Fluoxetine-treated and
      placebo-treated patients did not differ statistically significantly in the
      incidence of suicidality either during or after discontinuation of therapy.

PMID- 8253700
TI  - Association of fluoxetine and return of sexual potency in three elderly men.
AB  - BACKGROUND: Fluoxetine, a highly specific serotonin reuptake inhibitor, has been
      reported to cause sexual dysfunction in a minority of patients. Although priapism
      has been associated with other serotonergic antidepressants, no published reports
      have correlated restoration of sexual potency with use of fluoxetine. METHOD: The
      case histories of three geriatric patients treated with fluoxetine for depression
      or obsessive compulsive disorder are presented. RESULTS: Three patients with
      histories of impotence experienced a return of sexual potency after treatment
      with fluoxetine. In two of the cases, the patients had documented histories of
      vascular disease, which their internists had identified as the cause of their
      impotence. The improvement in sexual response was seemingly unrelated to
      abatement of depression or obsessive compulsive disorder, and there was no
      description of priapism by any of the patients. CONCLUSION: Sexual side effects
      of fluoxetine may be more variable than previously thought. Animal models showing
      paradoxical or opposing responses to serotonin-enhancing agents may apply to
      human sexual functioning as well.

PMID- 8253701
TI  - Akathisia and sertraline.

PMID- 8253702
TI  - Acute therapy of depression.
AB  - The acute therapy (the initial 8 weeks of treatment) of depression (including the
      whole spectrum of "less than major," "major," and "more than major") has been
      reviewed comparing the old tricyclics with the new generations (especially
      mianserin, moclobemide, and the serotonin selective reuptake inhibitors (SSRIs),
      i.e., citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline). The
      Hamilton Rating Scale for Depression has been used to measure clinical efficacy.
      Statistically, the method of meta-analysis has been applied. The results showed
      that the SSRIs and moclobemide are equal to the tricyclics. Mianserin is inferior
      to tricyclics as well as to SSRIs. The antidepressive profile of the SSRIs is
      nonsedation but still with anxiolytic effects. The safety profile of the SSRIs is
      much more benign than that of the tricyclics.

PMID- 8253703
TI  - The use of antidepressants for long-term treatment of recurrent depression:
      rationale, current methodologies, and future directions.
AB  - Present strategies for long-term treatment of major depressive disorder stem from
      the following three observations: the high frequency of recurrent depression, the
      length of a depressive episode, and the ability of antidepressants to prevent
      recurrences. Two different phases of long-term antidepressant treatment are now
      considered: continuation and a "true" maintenance or prophylactic phase.
      Moreover, it seems important to discriminate between relapse (from a previous
      episode) and recurrence (a new episode). However, there are some unresolved
      questions, such as (1) the duration of antidepressant treatment, (2) the type and
      posology of antidepressants to be used, and (3) some methodological aspects, such
      as the choice of comparators, definition of response, and combination with other
      therapies. This paper deals with all of these aspects, finally suggesting
      different prophylactic strategies in relation to factors like severity of
      symptoms, frequency of episodes, compliance, and susceptibility to side effects.

PMID- 8253704
TI  - The comparative pharmacology of new antidepressants.
AB  - This review attempts to critically assess the evidence regarding the relationship
      between the specificity of antidepressants in modulating different
      neurotransmitter systems and their therapeutic activity. Evidence from
      experimental and clinical studies suggests that all antidepressants and
      electroconvulsive shock therapy produce qualitatively similar adaptive changes in
      serotonergic, adrenergic, and possibly GABAergic and dopaminergic transmission
      following chronic treatment. Such adaptational changes parallel the onset of the
      therapeutic response. The relationship between the pharmacokinetics and the
      therapeutic efficacy and safety of the serotonin selective reuptake inhibitors
      (SSRIs) is considered with particular attention to fluoxetine, fluvoxamine,
      sertraline, and paroxetine. The primary difference between these drugs lies in
      their half-lives; fluoxetine and its major active metabolite norfluoxetine have a
      combined half-life exceeding 7 days. All the SSRIs are well tolerated with a low
      incidence of life-threatening side effects. Nausea and, rarely, vomiting occur
      quite frequently as a consequence of increased serotonergic activity in the
      gastrointestinal tract and possibly via central 5-HT3 receptors. The safety and
      prolonged efficacy of the SSRIs render them particularly beneficial for the long
      term treatment of the depressed patient. Evidence is provided that, in order to
      prevent relapse, depressed patients should be maintained on continuous
      antidepressant therapy for at least 1 year, and at the same dose as that required
      to treat the acute phase of the illness. The review concludes with a brief
      summary of the therapeutic use of the SSRIs in the treatment of panic attack,
      obsessive compulsive disorder, and bulimia with a brief comment on the different
      subtypes of serotonin receptors that may be involved.

PMID- 8253705
TI  - Antidepressant maintenance medications: when to discontinue and how to stop.
AB  - Most depressive disorders, once developed, have a lifetime course. For the
      majority of patients, the risk for future episodes increases as the number of
      past episodes increases. The length of the well interval between episodes becomes
      progressively shorter with each new episode. Those who are older at onset often
      have higher probabilities of relapse during future years if not maintained on
      treatment. As the number of episodes grows larger and the patient becomes older,
      severity often intensifies, treatment responsivity to conventional
      antidepressants may diminish or even disappear, and the destructive consequences
      of the disorder progressively worsen. This destructive lifetime pattern can be
      prevented in many if not most patients since antidepressant and other maintenance
      medications are being shown to be efficacious in preventing most future episodes
      of depression, maintaining euthymia, and preserving quality of life. On the basis
      of these and other still-developing findings (and with the recognition that
      maintenance strategies have been inadequately tested in depressed children and
      adolescents), reasonable clinical wisdom might suggest that lifetime
      pharmacologic maintenance may be indicated for patients 50 years or older at
      first episode, 40 years or older with two or more prior episodes, or for those
      with three or more prior episodes. "Maintenance" dosages need to be comparable to
      established "treatment" dosages until it is proven that lower doses are
      efficacious; such data now are lacking. When medication is selected for long-term
      treatment, strong considerations should be given to the agent's side effect
      profile, since compliance is essential for success.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8253706
TI  - Adverse drug reactions/interactions in maintenance therapy.
AB  - This paper begins with a brief review of the early onset, recidivism, and
      multiple consequences of recurrent major depressions. Increasing attention to
      these factors underscores the importance of long-term maintenance therapy.
      Successful maintenance rests on optimizing the risk:benefit profile for the
      patient. Literature is reviewed that the serotonin selective reuptake inhibitors
      exhibit a significantly lower discontinuation rate due to adverse events than do
      other conventional antidepressants. Adverse events clearly detract from patient
      compliance and, in turn, ultimately contribute to the risk of depressive
      recurrence. An overview of adverse events, in both short- and long-term anti
      depressant trial experience is provided. In addition, extended pharmacotherapy
      carries an increased probability of concomitant drug therapy. Relevant drug:drug
      interaction issues are reviewed, including specific attention to those mediated
      by the hepatic isoenzyme cytochrome P450 IID6. Lastly, long-term clinical trial
      experience with fluoxetine relative to short- and long-term emergence of adverse
      events and adverse event experience following drug discontinuation is presented.
      Overall fluoxetine adverse events do not increase with chronic administration.
      When side effects occur, they typically emerge early in the course of acute
      treatment and wane in the face of continued treatment. Upon drug discontinuation,
      these events usually reverse at a much faster pace than the drug's half-life. In
      conclusion, the importance of maintenance therapy in recurrent major depression
      is increasingly recognized as a critical care issue. To optimize a therapeutic
      outcome, the clinician is challenged to maximize patient compliance through
      depression awareness education, regular follow-up, minimization of adverse drug
      events, and sensitivity to other intercurrent psychosocial events.

PMID- 8253707
TI  - New antidepressants: use in high-risk patients.
AB  - This paper will review evidence on the safety and efficacy of new antidepressants
      in high-risk patients. Where available, data will be reviewed on the serotonin
      selective reuptake inhibitors (SSRIs), including fluoxetine, fluvoxamine,
      paroxetine, sertraline, and citalopram, and on the new reversible inhibitor of
      monoamine oxidase-A moclobemide.

PMID- 8253708
TI  - A primary care perspective on management of acute and long-term depression.
AB  - Major depressive disorder causing much social and physical dysfunction and risk
      of suicide is frequently seen in family practice, often presenting with somatic
      symptoms, sleep problems, or anxiety. Correct diagnosis allows prompt treatment
      with decreased morbidity and mortality. The new serotonin selective reuptake
      inhibitors (SSRIs), like fluoxetine, provide the family practitioner with
      antidepressants that are devoid of the unwanted and sometimes dangerous side
      effects of the older drugs. The SSRIs have a more benign side effect profile and
      are much safer in overdose. Patient education is essential regarding the medical
      nature of this disorder of the nervous system and its effective treatment with
      pharmacotherapy and need to continue full-dose maintenance therapy for 6 to 9
      months after complete remission of the depressive episode to prevent relapse.
      Recognition of the recurrent nature of this illness is mandatory, and chronic
      (lifetime) full-dose prophylactic therapy is often necessary. The SSRIs assist in
      compliance to treatment.

PMID- 8253709
TI  - The status of medical illustration in Western Europe and Australia.
AB  - In an effort to better determine how medical illustration has evolved overseas,
      contact was established with Western European and Australian medical
      illustrators, their professional organizations, and their schools for medical
      illustration. Information was gathered from returned letters and questionnaires.
      Data indicating the illustrator's sex, age, education, employment, job duties,
      techniques employed, subject matter, contact with other illustrators, and
      professional membership were collected. An analysis of the trends in each of the
      above-stated areas showed that the educational backgrounds, professional
      organizations, job responsibilities, and wages were similar to those of medical
      illustrators in the United States.

PMID- 8253710
TI  - Printed materials for an aging population: design considerations.
AB  - By the year 2020, 25% of the American population will be fifty-five or older. As
      this population ages, changes within the aging eye will necessitate changes in
      the way we present text, since approximately 85% of all learning occurs through
      vision. Educators need to become aware of these changes and begin designing
      written materials that can communicate effectively with this population. This
      paper includes information about some of the problems associated with the aging
      eye and design strategies that can enable the older adult to continue learning,
      working, and enjoying the written word.

PMID- 8253711
TI  - Type IV collagen: structure, gene organization, and role in human diseases.
      Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis.

PMID- 8253712
TI  - Angiotensin II induces 3CH134, a protein-tyrosine phosphatase, in vascular smooth
      muscle cells.
AB  - Angiotensin II is a potent growth factor for vascular smooth muscle cells and
      shares many signal transduction mechanisms with mitogens, including stimulation
      of mitogen-activated protein (MAP) kinases and protein tyrosine phosphorylation.
      Regulation of tyrosine phosphorylation involves both protein-tyrosine kinases and
      protein-tyrosine phosphatases (PTPases). To investigate the role of PTPases in
      angiotensin II-mediated events, we studied the expression of a transcriptionally
      regulated PTPase, 3CH134, which has selective activity toward MAP kinase.
      Angiotensin II rapidly induced 3CH134 mRNA (30 min maximum) in a concentration
      dependent manner (100 nM maximum). Platelet-derived growth factor, alpha
      thrombin, hydrogen peroxide, phorbol 12-myristate 13-acetate, and ionomycin also
      induced 3CH134 but to levels lower than angiotensin II. Induction of 3CH134 by
      angiotensin II was partially inhibited after down-regulating protein kinase C but
      was fully inhibited after chelating intracellular Ca2+. Treatment with both
      phorbol 12-myristate 13-acetate and ionomycin induced 3CH134 mRNA to levels seen
      with angiotensin II, indicating that Ca2+ mobilization and protein kinase C
      activation can act synergistically to induce 3CH134. Angiotensin II stimulated
      3CH134 protein synthesis after 1 h as measured by immunoprecipitation of 3CH134
      from [35S]methionine-labeled cells using affinity-purified antibodies. These
      results establish 3CH134 as a dynamically regulated, immediate early gene in
      vascular smooth muscle cells and suggest a role for PTPases in regulating
      angiotensin II-stimulated events mediated by MAP kinases and tyrosine kinases.

PMID- 8253713
TI  - In vitro heme O synthesis by the cyoE gene product from Escherichia coli.
AB  - The cytochrome bo complex is a heme-copper terminal quinol oxidase in the aerobic
      respiratory chain of Escherichia coli and contains low spin heme B, high spin
      heme O and CuB as the redox metal centers in subunit I. Based on site-directed
      mutagenesis studies on the cyoE gene in the cytochrome bo operon, we have
      postulated that the cyoE gene encodes a protoheme IX farnesyltransferase (heme O
      synthase) (Saiki, K., Mogi, T., and Anraku, Y. (1992) Biochem. Biophys. Res.
      Commun. 189, 1491-1497). The present study demonstrates that the CyoE protein is
      localized in the cytoplasmic membrane and that the CyoE-overproduced membranes
      efficiently catalyze a conversion of exogenous ferrous protoheme IX and farnesyl
      diphosphate to heme O in the presence of divalent cations such as Mg2+ or Ca2+.
      Thus, the cyoABCDE operon in E. coli encodes not only subunits of the cytochrome
      bo complex but also heme O synthase that is specifically required for functional
      expression of the bo-type quinol oxidase. Heme O seems to be an intermediate in
      heme A biosynthesis.

PMID- 8253714
TI  - Identification of the peptide binding domain of hsc70. 18-Kilodalton fragment
      located immediately after ATPase domain is sufficient for high affinity binding.
AB  - Recombinant hsc70, a purified glutathione S-transferase (GST) fusion protein
      containing the C-terminal domain of hsc70 (GST-Ct), and an internal 18-kDa
      polypeptide located immediately after the 44-kDa ATPase domain of hsc70 were
      investigated for their peptide binding properties. The dissociation constants of
      the S-peptide for native hsc70 (Kd = 5-8 microM), GST-Ct (Kd = 6.5 microM), and
      the 18-kDa fragment (Kd = 8.1 microM) are virtually identical. In addition,
      polylysine and (Pro-Pro-Gly)5 do not show high affinity toward hsc70, GST-Ct, and
      the 18-kDa fragment, whereas peptide GT4 and P3a show comparably high affinity
      toward these polypeptides. These observations indicate that the peptide binding
      domain of hsc70 is confined in the internal 18-kDa fragment.

PMID- 8253715
TI  - Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and
      inhibition of the hydrolysis by ATP.
AB  - Cyclic ADP-ribose (cADPR) has been recently shown to be generated in pancreatic
      beta-cells by glucose stimulation, serving as a second messenger for Ca2+
      mobilization in the endoplasmic reticulum in the process of insulin secretion
      (Takasawa, S., Nata, K., Yonekura, H., and Okamoto, H. (1993) Science 259, 370
      373). In the present study, we isolated a cDNA for CD38, which has been reported
      to be a human leukocyte antigen, from a human insulinoma and expressed the cDNA
      in COS-7 cells. CD38 expression was observed in the plasma membrane and the
      microsome fractions of the COS-7 cells. When we incubated the plasma membrane
      fraction with NAD+ and analyzed the reaction products by high pressure liquid
      chromatography, the formation of cADPR was observed in addition to the ADP-ribose
      (ADPR) formation. When the plasma membrane fraction was incubated with cADPR,
      cADPR was converted to ADPR stoichiometrically. These results suggest that CD38
      has both cADPR-forming and -hydrolyzing activities. Moreover, we found that ATP
      (2-10 mM), generated in the glucose metabolism in beta-cells, inhibited the cADPR
      hydrolyzing activity, resulting in the increased formation of cADPR. These
      findings indicate a role for CD38 in the synthesis and hydrolysis of cADPR in the
      process of insulin secretion in pancreatic beta-cells.

PMID- 8253716
TI  - Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation
      of insulin receptor and its substrates.
AB  - Tumor necrosis factor-alpha (TNF) has recently been shown to induce insulin
      resistance. We have examined the possible effect of TNF on the early events in
      insulin transmembrane signaling. Incubation of the insulin-sensitive rat hepatoma
      Fao cells with 5 nM TNF for 1 h led to a 65% decrease in insulin-induced tyrosine
      phosphorylation of both the insulin receptor beta-subunit and IRS-1, its major
      cytosolic substrate. TNF-induced impairment of tyrosine phosphorylation was
      maximal at 0.5 nM and was not accompanied by any reduction in insulin binding.
      Sixteen hours of TNF incubation led to further impairment in insulin-induced
      tyrosine phosphorylation of these proteins. Our findings suggest that TNF may
      exert its anti-insulin effect by interrupting the early insulin-stimulated
      tyrosine phosphorylation events, which are crucial to insulin transmembrane
      signaling.

PMID- 8253717
TI  - Cloning and expression of a human CDC42 GTPase-activating protein reveals a
      functional SH3-binding domain.
AB  - CDC42, a member of the Rho family of small GTP-binding proteins, regulates
      cytoskeletal rearrangements required for cell division. Activating mutations in
      CDC42 that are refractory to GTPase activation confer a phenotype of large,
      multinucleated cells. Like other small GTP-binding proteins, CDC42 is activated
      by a guanosine exchange factor and inactivated by a GTPase-activating protein
      (GAP). An unidentified 25-kDa platelet protein has been shown to function as a
      specific CDC42GAP. Here we report the cloning of a cDNA encoding this GAP from a
      human platelet-precursor cell line. Sequence analysis reveals the presence of
      three consensus box regions characteristic of rhoGAPs. A glutathione S
      transferase fusion protein containing the three boxes derived from the new clone
      strongly stimulated the GTPase activity of CDC42 but was much less effective on
      other Rho proteins. This indicates that the cDNA clone encodes a specific GAP for
      CDC42. Sequence analysis also reveals a potential proline-rich Src homology 3
      (SH3)-binding domain preceding the first consensus box. Binding experiments show
      that this motif can interact with the SH3 domains of p85 alpha and of c-Src.
      Thus, CDC42GAP may function as a link between CDC42 and other signaling pathways.

PMID- 8253718
TI  - The adenovirus-mediated delivery of a reporter gene permits the assessment of
      androgen receptor function in genital skin fibroblast cultures. Stimulation of Gs
      and inhibition of G(o).
AB  - Defects in the androgen receptor cause a spectrum of abnormalities in genetic
      males ranging from phenotypic women with testicular feminization to men with
      minor defects in fertility and/or virilization. The diagnosis of androgen
      resistance can be quite cumbersome, including analysis of the family history,
      karyotyping, endocrine studies, measurement of androgen binding in genital skin
      fibroblasts, and, in some instances, sequencing of mutant cDNAs. Furthermore,
      androgen-binding studies may be normal in patients with qualitative receptor
      abnormalities or mutations in the DNA-binding domain of the receptor. To
      circumvent these difficulties, we have used a recombinant adenovirus to deliver
      an androgen-responsive reporter gene (mouse mammary tumor virus-luciferase) to
      fibroblasts cultured from genital skin from 12 normal controls and from eight
      individuals with complete testicular feminization. Following incubation with
      androgen (2 nM mibolerone) for 72 h, luciferase activity in normal fibroblasts
      increased > 10-fold (range 11-200-fold) in a manner that corresponded with the
      level of androgen receptor detected in ligand-binding assays. By contrast,
      luciferase activity increased negligibly in fibroblasts from individuals with
      testicular feminization (average = 1.2-fold increase). This assay permits a
      direct assessment of endogenous androgen receptor function in cells and should be
      a powerful aid in the diagnosis of androgen resistance.

PMID- 8253719
TI  - Opposite coupling of prostaglandin E receptor EP3C with Gs and G(o). Stimulation
      of Gs and inhibition of G(o).
AB  - We recently identified four isoforms of bovine prostaglandin E receptor EP3
      subtype, which are coupled to different signaling pathways; EP3A is coupled to
      inhibition of adenylate cyclase, while EP3B and EP3C are coupled to its
      stimulation and EP3D is coupled to phosphatidylinositol turnover, in addition to
      the adenylate cyclase system (Namba, T., Sugimoto, Y., Negishi, M., Irie, A.,
      Ushikubi, F., Kakizuka, Ito, S., A., Ichikawa, A., and Narumiya, S. (1993) Nature
      365, 166-170). We examined here the identity of coupled G proteins and their
      regulation by one of the isoforms, EP3C, in the membranes of EP3C cDNA
      transfected Chinese hamster ovary cells. M&B 28767, an EP3 agonist, stimulated
      the GTPase activity in the pertussis toxin (PT)-treated cell membrane, but
      inhibited it in the cholera toxin (CT)-treated cell membrane, while the agonist
      neither stimulated nor inhibited it in the both PT- and CT-treated cell membrane.
      In the PT- and CT-treated cell membrane reconstituted with various G proteins,
      M&B 28767 inhibited the GTPase activity of G(o), but stimulated that of Gs. On
      the other hand, M&B 28767 did not affect the GTPase activity of Gi1, Gi2, or Gi3.
      M&B 28767 increased the apparent affinity of G(o) for GDP without any change in
      that for GTP, as assessed by displacement of [35S]GTP gamma S (guanosine 5'-O-(3
      thiotriphosphate)) binding to G(o). In contrast, M&B 28767 increased the apparent
      affinity of Gs for GTP but decreased that for GDP. These results demonstrated
      that the EP3 receptor isoform is coupled to two different G proteins, and
      oppositely regulates their activities, inhibition of G(o), and stimulation of Gs.

PMID- 8253720
TI  - Prolonged desensitization of the human endothelin A receptor in Xenopus oocytes.
      Comparative studies with the human neurokinin A receptor.
AB  - Human endothelin (ET) A receptor (hETAR) is a G-protein-mediated receptor that
      binds ET1 with high affinity and ET2 and ET3 with lower affinities. ET1 is the
      most potent endogenous vasoconstrictor known at this time. When expressed in
      Xenopus laevis oocytes, hETAR is rapidly desensitized after stimulation with ET1.
      This desensitization lasts 90-110 min. Human neurokinin A (hNKAR) and human
      serotonin type 2 receptors were also expressed in the Xenopus system for
      comparison to hETAR. hNKAR desensitizes for 25-35 min, while the serotonin
      receptor does not appear to desensitize. To examine the role of the cytoplasmic
      tail of hETAR in desensitization, deletion mutations were constructed which
      remove 11, 36, and 51 amino acids from the cytoplasmic tail. The mutations
      removing 11 and 36 residues were functional, but the mutation removing 51 amino
      acids was not functional. The two functional mutations have a resensitization
      time similar to that of hETAR. In summary, the prolonged desensitization time of
      hETAR is unique for G-protein-mediated receptors and may attenuate the adverse
      physiological effects of the endothelin family. In addition, the cytoplasmic tail
      of hETAR does not appear to play a role in desensitization or resensitization of
      this receptor.

PMID- 8253721
TI  - The regulation of store-dependent Ca2+ influx in HL-60 granulocytes involves GTP
      sensitive elements.
AB  - In granulocytes, emptying of intracellular Ca2+ stores activates Ca2+ influx
      across the plasma membrane. To study the putative role of GTP-binding proteins in
      this process, we have introduced non-hydrolyzable guanosine phosphate analogues
      into the cytosol of non-permeabilized HL-60 granulocytes using an endocytosis
      hypoosmotic shock procedure. At the cytosolic concentrations obtained (100-500
      microM), neither guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) nor guanosine
      5'-3-O-(thio)diphosphate (GDP beta S) affected basal [Ca2+]i. Ca2+ release in
      response to the receptor agonist fMet-Leu-Phe, the Ca(2+)-ATPase inhibitor
      thapsigargin, or the Ca2+ ionophore ionomycin was also unaffected by GTP gamma S
      or GDP beta S. In contrast, the activation of the Ca2+ influx pathway by fMet-Leu
      Phe or by thapsigargin was blocked by GTP gamma S but not by GDP beta S. The GTP
      gamma S effect was mimicked by NaF. The GTP gamma S and NaF effects were
      independent of protein kinase C activation and actin polymerization. Our results
      demonstrate that a GTP-sensitive element is involved in the signaling between
      intracellular Ca2+ stores and plasma membrane Ca2+ channels. The identical
      effects of GTP gamma S and NaF suggest that the GTP-sensitive element is a
      heterotrimeric G-protein.

PMID- 8253722
TI  - Expression of an oncogenic rasHa gene in murine keratinocytes induces tyrosine
      phosphorylation and reduced activity of protein kinase C delta.
AB  - Murine keratinocytes expressing an oncogenic rasHa gene produce benign tumors in
      vivo and demonstrate altered responses to phorbol esters in vitro. Cultured
      keratinocytes transduced with the v-rasHa gene (v-rasHa keratinocytes) are
      resistant to Ca(2+)-induced terminal differentiation, a process that is dependent
      on protein kinase C (PKC) activation in normal keratinocytes. Five PKC isoforms
      expressed in keratinocytes (alpha, delta, epsilon, zeta, and eta) were examined
      for quantitative or qualitative changes in v-rasHa-transformed cells. No
      quantitative changes were detected, but PKC delta was tyrosine-phosphorylated in
      v-rasHa keratinocytes and in benign neoplastic keratinocyte cell lines expressing
      an activated allele of the c-rasHa gene. Analysis of phosphorylated and non
      phosphorylated forms of PKC delta from keratinocytes indicated that
      phosphorylated PKC delta was not stimulated by phorbol ester treatment. The
      protein kinase inhibitor staurosporine was able to induce differentiation in v
      rasHa keratinocytes and benign tumor cell lines, and concomitantly tyrosine
      phosphorylation of PKC delta decreased. This interaction between tyrosine kinases
      and PKC delta in cells expressing an oncogenic rasHa gene may represent a
      molecular block to differentiation in neoplastic keratinocytes.

PMID- 8253723
TI  - Trp221 is involved in the protective effect of elongation factor eEF-2 on the
      ricin/alpha-sarcin site of the ribosome.
AB  - Elongation factor eEF-2 treated by N-bromosuccinimide under conditions which
      oxidize 2 Trp residues (Trp343 and Trp221) is inactivated in ribosome-dependent
      GTP hydrolysis and polyphenylalanine synthesis, and inactivation correlates with
      the specific oxidation of Trp221 (Guillot, D., Penin, F., Di Pietro, A., Sontag,
      B., Lavergne, J. P., and Reboud, J. P. (1993) J. Biol. Chem. 268, 20911-20916).
      It is shown here that this oxidation prevents neither GTP binding to eEF-2 nor
      the formation of the ribosome-eEF-2-GPP(NH)P complex, but that oxidized eEF-2 is
      no longer able to protect ribosomes against ricin inactivation. These
      observations suggest that Trp221 or an amino-acid sequence containing this
      residue interacts with the 28 S rRNA loop including the GAGA sequence, which is
      the target of ricin. Such a hypothesis is discussed in relation with data on RNA
      recognition motifs described in different proteins.

PMID- 8253724
TI  - Sphingomyelin transport to the cell surface occurs independently of protein
      secretion in rat hepatocytes.
AB  - The transport of sphingomyelin from its site of synthesis, in the cis/medial
      Golgi, to the plasma membrane has been investigated in monolayer cultures of rat
      hepatocytes. Sphingomyelin was synthesized intracellularly from [methyl
      3H]choline, and the arrival of sphingomyelin at the plasma membrane was monitored
      by treatment of the cells with sphingomyelinase, which hydrolyzed only
      sphingomyelin at the cell surface. When hepatocytes were maintained at
      temperatures from 5 to 37 degrees C, both protein secretion and sphingomyelin
      trafficking to the cell surface were inhibited at low temperatures, especially at
      temperatures below 25 degrees C. Treatment of cells with the energy poison
      potassium cyanide prevented protein secretion and reduced the incorporation of
      [3H]choline into sphingomyelin, but did not affect the percentage of newly
      synthesized sphingomyelin that was transported to the cell surface. Brefeldin A
      and monensin, both of which disrupt protein movement through the Golgi apparatus,
      were used to evaluate the mechanism of transport of sphingomyelin to the plasma
      membrane. Although brefeldin A and monensin each effectively blocked protein
      secretion, sphingomyelin movement to the cell surface was not inhibited, even
      though sphingomyelin synthesis normally occurs in the Golgi. We conclude that the
      most likely mechanism of sphingomyelin transport to the cell surface is a vesicle
      mediated process (because of the known topology of sphingomyelin synthesis and
      distribution). However, the putative vesicles that are involved in the movement
      of sphingomyelin to the plasma membrane are distinct from those that transport
      proteins for secretion. In addition, the route of trafficking of sphingomyelin to
      the plasma membrane is not one that requires an obligatory passage through the
      Golgi apparatus.

PMID- 8253725
TI  - Binding of encephalomyocarditis virus RNA polymerase to the 3'-noncoding region
      of the viral RNA is specific and requires the 3'-poly(A) tail.
AB  - An in vitro RNA bandshift assay has been developed to demonstrate the binding of
      purified recombinant encephalomyocarditis (EMC) virus RNA-dependent RNA
      polymerase (3Dpol) to the 3'-noncoding region (NCR) and 30 nucleotides of the
      adjacent 3'-terminal poly(A) tail (3'-NCR(A)) of EMC virus RNA. The binding of
      3Dpol to the 3'-NCR(A) fragment was specific since four other unrelated proteins
      including an RNA polymerase did not bind, and unlabeled 3'-NCR(A), but not alpha
      globin mRNA, tRNA, or pure poly(A), competed with radiolabeled 3'-NCR(A) for
      binding. Surprisingly, 3Dpol failed to bind to the 3'-NCR of EMC virus RNA
      lacking the poly(A) tail. The results together show that EMC virus RNA template
      specificity depends only on 3Dpol, the 3'-NCR, and the poly(A) tail. This
      suggests that 3'-poly(A) is essential for viral RNA template selection by the EMC
      virus RNA polymerase.

PMID- 8253726
TI  - Inactivation of phytochrome- and phycobiliprotein-chromophore precursors by rat
      liver biliverdin reductase.
AB  - The phytochrome chromophore precursor, 3E-phytochromobilin, and the
      phycobiliprotein chromophore precursors, 3E-phycocyanobilin and 3E
      phycoerythrobilin, are enzymatically converted to novel rubinoid products by
      purified rat liver biliverdin reductase. Phytochromobilin and phycocyanobilin are
      particularly good substrates for biliverdin reductase with Km and Vmax values
      very similar to those of the natural substrate, biliverdin IX alpha.
      Phycoerythrobilin is the least preferred of the three bilin substrates. 1H NMR
      spectroscopy of phycocyanorubin, the product of phycocyanobilin catalysis by
      biliverdin reductase, and comparison of absorption spectra of all three rubinoid
      products reveal that the C10 methine bridge is selectively reduced by biliverdin
      reductase without altering the A-ring ethylidene substituent. In vitro
      phytochrome assembly experiments demonstrate that the phytorubin products do not
      form photoactive adducts with recombinant apophytochrome. These results suggest
      that ectopic expression of biliverdin reductase in plants will prevent assembly
      of the functional photoreceptor and thus will potentially alter light-mediated
      plant growth and development.

PMID- 8253727
TI  - Dependence of hepatocytic autophagy on intracellularly sequestered calcium.
AB  - Autophagic sequestration of endogenous lactate dehydrogenase or electroinjected
      [3H]raffinose in isolated rat hepatocytes was strongly suppressed by the Ca2+
      chelator EGTA, unless the cells had previously been electroloaded in the presence
      of high concentrations of Ca2+ (1.2 mM). The extracellular Ca2+ chelator bis-(o
      aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) and the intracellular
      Ca2+ chelator BAPTA/tetra(acetoxymethyl)-ester (BAPTA/AM) both inhibited
      autophagy to the same extent as did EGTA. Inhibitors of Ca(2+)-activated protein
      kinases (KN-62, H-7, W-7) had little or no effect on autophagy, indicating that
      the Ca2+ requirement of autophagy was not mediated by such kinases. Agents that
      elevate cytosolic Ca2+ by releasing Ca2+ from intracellular stores, like
      thapsigargin, 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) and the
      ionophores A23187 and ionomycin, inhibited autophagy strongly, implicating
      depletion of sequestered rather than of cytosolic intracellular Ca2+ as a common
      mechanism of inhibition. Lysosomal (propylamine-sensitive) protein degradation,
      known to be largely autophagy-dependent, was inhibited by thapsigargin and
      tBuBHQ. Thapsigargin had no effect on cellular ATP levels, but all agents tested
      (thapsigargin, tBuBHQ, ionophores) inhibited protein synthesis. Our results
      suggest that autophagy, like protein synthesis, is dependent on the presence of
      Ca2+ in some intracellular storage compartment.

PMID- 8253728
TI  - Inefficient degradation of triglyceride-rich lipoprotein by HepG2 cells is due to
      a retarded transport to the lysosomal compartment.
AB  - Binding studies at 37 degrees C showed that lipoprotein lipase-treated very low
      density lipoproteins (LPL-VLDL) and very low density lipoproteins (VLDL), once
      taken up via the low density lipoprotein (LDL) receptor, are poorly degraded by
      HepG2 cells as compared with LDL. Determination of the initial endocytotic rate
      for LPL-VLDL and VLDL as compared to LDL shows that LPL-VLDL and VLDL are
      internalized at a similar rate as LDL. Incubation of cells with labeled LDL, LPL
      VLDL, and VLDL at 18 degrees C for 4.5 h resulted in the accumulation of these
      particles in the early endosomes, without subsequent transport to the lysosomes
      and degradation. After washing the cells and a temperature shift to 37 degrees C,
      the labeled LDL present in the early endosomes is transported to the lysosomal
      compartment almost completely within 15 min. Strikingly, for LPL-VLDL and for
      VLDL, only about 50% or less of the label was moved to the lysosomal compartment
      within 45 min. However, once present in the lysosomes, VLDL and LPL-VLDL are
      degraded about 1.6-fold more rapidly than LDL. Retroendocytosis accounts for less
      than 10% of the internalized LDL, whereas a higher rate of retroendocytosis, up
      to 20 and 40%, respectively, was observed for LPL-VLDL and VLDL. To evaluate the
      effect of the inefficient transport of VLDL and LPL-VLDL to the lysosomal
      compartment on cellular cholesterol homeostasis, acyl-CoA:cholesterol
      acyltransferase (ACAT) activity was measured. Incubation with 30 micrograms/ml of
      LDL induced a 2.5-fold increase in ACAT activity, whereas the incubation with
      similar amounts of both VLDL and LPL-VLDL failed to stimulate this enzyme. We
      conclude that both a slower transport to the lysosomal compartment and a higher
      rate of retroendocytosis, possibly as the consequence of the longer residence
      time in the early endosomes, are responsible for the poor degradation of VLDL and
      LPL-VLDL by HepG2 cells.

PMID- 8253729
TI  - Mitogenic signaling mechanisms of human cementum-derived growth factors.
AB  - Cementum-derived growth factor (CGF) is a M(r) 23,000 protein, which is
      sequestered in the mineralized matrix of tooth cementum. We have investigated the
      mitogenic signaling reactions induced by CGF using quiescent human gingival
      fibroblasts as target cells. Cells activated with CGF were compared with those
      treated with CGF plus epidermal growth factor (EGF) and other growth factors. CGF
      caused a transient increase in cytoplasmic Ca2+ concentration, and this was
      accompanied by enhancement of membrane protein kinase C activity, myelin basic
      protein and S6 kinase activities, inositol phosphate levels, and activation of c
      fos and jun-B gene expression. Membranes obtained from cells activated with CGF
      contained several protein bands, which cross-reacted with antiphosphotyrosine
      antibody; however, proteins corresponding to a putative phosphorylated CGF
      receptor were not detected. DNA synthesis induced by CGF was inhibited by 65% in
      cells treated with pertussis toxin but only 25-29% in cultures exposed to H7 or
      12-O-tetradecanoylphorbol-13-acetate; these values were different from those
      obtained when EGF, PDGF, or fetal bovine serum were used as mitogens. CGF and TGF
      beta, but not EGF, caused an increase of PDGF-A chain mRNA expression 4 h after
      mitogen addition. However, while CGF was mitogenic for gingival fibroblasts, TGF
      beta was not. Kinetics of DNA stimulation and experiments with anti-PDGF
      antibodies indicated that PDGF-A expression does not contribute significantly to
      CGF-induced DNA synthesis. When the stimulation of various signaling pathways
      induced by CGF and other growth factors was compared, the pattern of stimulation
      by CGF was different from other growth factors. The characteristic signaling
      reactions of CGF are likely to be important components of the mechanisms that
      regulate the formation and regeneration of cementum and adjacent connective
      tissues.

PMID- 8253730
TI  - Biosynthesis of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L
      threonine of cyclosporin A. Identification of 3(R)-hydroxy-4(R)-methyl-6(E)
      octenoic acid as a key intermediate by enzymatic in vitro synthesis and by in
      vivo labeling techniques.
AB  - The biosynthesis of (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (abbreviation:
      Bmt, systematic name: 2(S)-amino-3(R)-hydroxy-4(R)-methyl-6(E)-octenoic acid) is
      proposed to involve two principal phases: the formation of a polyketide backbone
      and a subsequent transformation process to the final product. Here we report on
      the identification of 3(R)-hydroxy-4(R)-methyl-6(E)-octenoic acid as the end
      product of the first phase. The primary indication of 3(R)-hydroxy-4(R)-methyl
      6(E)-octenoic acid as the key intermediate in the proposed biosynthetic route
      came from in vivo labeling studies with [1-13C,18O2]acetate, demonstrating
      retention of 18O in the 3-hydroxy group. Final identification of this
      intermediate in in vitro polyketide assays with enriched enzyme fractions of
      Tolypocladium niveum was achieved after development of highly sensitive and
      specific detection methods and by use of synthetic reference substances. Two
      additional methylated in vitro products could be detected and characterized as
      4(R)-methyl-(E,E)-2,6-octadienoic acid and 4(R)-methyl-6(E)-octenoic acid by
      liquid chromatography-mass spectrometry analysis and comparison with synthetic
      reference samples. Their relevance for Bmt biosynthesis is discussed. Bmt
      polyketide synthase shows optimal activity at substrate concentrations of 200
      microM acetyl-CoA, 150 microM malonyl-CoA, and 200 microM S-adenosylmethionine,
      around pH 7 and at 35 degrees C. Interestingly the Bmt backbone is released from
      the enzyme as a coenzyme A thioester, suggesting that subsequent transformation
      to Bmt takes place upon this activated intermediate.

PMID- 8253732
TI  - Modulation of protein tyrosine phosphorylation during G1/S transition in
      activated human T-lymphoblasts.
AB  - We report that in activated human T-lymphoblasts synchronized early in the G1
      phase of the cell cycle, addition of interleukin 2 (IL-2) stimulates transition
      into S-phase in conjunction with specific and reproducible protein tyrosine
      phosphorylation events. Prominent among these was de novo phosphorylation of the
      p56lck tyrosine kinase, which appeared as a single polypeptide on SDS
      polyacrylamide gel electrophoresis prior to the addition of IL-2, but as a
      doublet of approximately 56 and 59 kDa 3 h after IL-2 addition. Although the lck
      polypeptide doublet persisted into S-phase, the 59-kDa form was virtually
      undetectable in T-lymphoblasts in log phase growth. In T-lymphoblasts
      metabolically labeled with 32Pi, antiphosphotyrosine antisera identified a major
      56-kDa tyrosine-phosphorylated protein, whereas antisera to lck showed that
      phosphorylation of lck occurred on both the 56- and 59-kDa forms. Phosphoamino
      acid analyses identified phosphoserine as the major phosphoamino acid on both of
      the lck polypeptides, although small amounts of phosphotyrosine were also
      detected on the 56-kDa form. Immune complex kinase assays revealed that only the
      lower band of the lck doublet exhibited autocatalytic activity. Furthermore, the
      59-kDa form neither displayed autocatalytic activity, nor was it a substrate for
      phosphorylation by the 56-kDa form. We conclude that entry into S-phase in
      activated human T-lymphoblasts is associated with tyrosine phosphorylation of a
      limited number of proteins and suggest that p56lck activity is regulated during
      G1/S.

PMID- 8253731
TI  - Partial activation of the pyruvate dehydrogenase kinase by the lipoyl domain
      region of E2 and interchange of the kinase between lipoyl domain regions.
AB  - The binding of the pyruvate dehydrogenase (E1) component and the E1-specific
      kinase to the core-forming dihydrolipoyl acetyltransferase (E2) component
      facilitates a severalfold enhancement in the rate at which the kinase
      phosphorylate E1 (i.e. versus free kinase phosphorylating free E1). The kinase
      and E1 associate with small exterior linker region-connected domains in the E2
      structure. The kinase binds to one of two lipoyl domains, and the E1 component
      binds to a domain in E2"s structure between the lipoyl domain region and the
      inner domain. Sixty of the latter domains assemble to form a dodecahedron-shaped
      inner core. Binding of the kinase to a detached lipoyl domain region enhanced
      kinase activity. This bi-lipoyl domain fragment induced a 2-fold enhancement in
      the slow rate of phosphorylation of peptide substrate and intact E260 gave only a
      50% higher rate. In contrast, the lipoyl domain fragment gave only a 40%
      enhancement in the faster rate of phosphorylation of E1; whereas the rate of
      phosphorylation of E1 was markedly increased (4-10-fold depending on conditions)
      by kinase interaction with the intact E2 core. Binding of E1 to an E2 structure
      lacking only the bi-lipoyl domain region did not enhance kinase activity. Thus,
      binding of the kinase to the lipoyl domain region elicits a structural change
      which enhances kinase activity; however, other processes are required to explain
      the very large enhancement in phosphorylation of E1 effected by intact E2 core.
      Among the latter is a need for a mechanism allowing one kinase molecule to
      phosphorylate many E1 tetramers, whereas both E1 and the kinase stay bound to the
      oligomeric E2 core (i.e. phosphorylation appears to be much faster than the
      dissociation of either the kinase or E1 tetramers from E260 core). Exposure of
      kinase bound to the lipoyl domain fragment to intact E2 core for 10 s allowed a
      transition to a maximal (7-fold) activation of the kinase. In the opposite
      direction, an increasing level of the free bi-lipoyl domain fragment rapidly
      reduced, in a concentration-dependent manner the activity of kinase bound
      initially to intact E2. The data strongly support kinase transfer between free
      lipoyl domains and the intact E2 core and fit about a 12-fold tighter binding of
      the kinase to intact E2 cores over binding to free lipoyl domains. Such an
      interchange of the kinase between these E2 structures was confirmed by sucrose
      gradient studies.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8253733
TI  - Studies on the inhibitory action of mercury upon proteinase K.
AB  - In proteinase K, Cys73 is located "below" the imidazole of the active site His69.
      In a 2.4-A resolution x-ray crystal structure of the complex formed between the
      enzyme and HgAc2, two Hg(II) positions are found: a fully occupied site,
      covalently bound to Cys73 (S gamma), which disrupts the catalytic triad (Asp39
      His69-Ser224), and a 2-fold disordered (25 and 35% occupancy), noncovalent
      complexation to His72, Cys73, and Thr76 of lower affinity. The enzyme is
      inhibited noncompetitively at low concentrations and competitively above
      stoichiometric concentrations of Hg(II), but it retains 7% residual activity.
      This can be rationalized if the molecule is flexible enough to permit transient
      formation of the catalytic triad. Except for the active site, only minor
      structural changes are observed upon binding of Hg(II), but the thermal stability
      is reduced by 4 degrees C.

PMID- 8253734
TI  - PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of
      the enzyme.
AB  - Overexpressed PIF1 DNA helicase was purified from mitochondria to near
      homogeneity. Its ATPase and unwinding properties were characterized. The enzyme
      specifically utilizes ATP (or dATP) and MgCl2 (and to a lesser extent MnCl2).
      ATPase activity requires single-stranded DNA as an effector, duplex DNA being 100
      fold less effective. The Keff, defined as the concentration of DNA required to
      achieve half-maximal ATPase activity, does not depend on single-stranded DNA
      length. Long duplex DNAs are poorly unwound and, moreover, dilution of the enzyme
      and its DNA substrate in the assay decreases DNA helicase activity. These data
      indicate that PIF1 helicase is a distributive enzyme, frequently turning from one
      DNA molecule to another. When forked substrates are used, unwinding by PIF1 is
      markedly stimulated. The enzyme has a sedimentation coefficient of 6.5 S,
      suggesting that it exists as a monomer in solution.

PMID- 8253735
TI  - DNA-induced conformational changes in RecA protein. Evidence for structural
      heterogeneity among nucleoprotein filaments and implications for homologous
      pairing.
AB  - We have used circular dichroism as a probe to characterize the solution
      conformational changes in RecA protein upon binding to DNA. This approach
      revealed that RecA protein acquires significant amounts of alpha-helix upon
      interaction with DNA. These observations, consistent with the data from crystal
      structure (Story, R. M., Weber, I., and Steitz, T. (1992) Nature 355, 318-325),
      support the notion that some basic domains including the DNA binding motifs of
      RecA protein are unstructured and might contribute to the formation of alpha
      helix. A comparison of nucleoprotein filaments comprised of RecA protein and a
      variety of DNA substrates revealed important structural heterogeneity. The most
      significant difference was observed with poly(dG). poly(dC) and related polymers,
      rich in GC sequences, which induced minimal amounts of alpha-helix in RecA
      protein. The magnitude of induction of alpha-helix in RecA protein, which
      occurred concomitant with the production of ternary complexes, was 2-fold higher
      with homologous than heterologous duplex DNA. Most importantly, the stimulation
      of ATP hydrolysis by high salt coincided with that of the induction of alpha
      helix in RecA protein. These conformational differences provide a basis for
      thinking about the biochemical and structural transitions that RecA protein
      experiences during the formal steps of presynapsis, recognition, and alignment of
      homologous sequences.

PMID- 8253737
TI  - Enzymatic characterization of the individual mammalian primase subunits reveals a
      biphasic mechanism for initiation of DNA replication.
AB  - The enzymatic mechanism of primase was investigated using Escherichia coli and
      baculoviral overexpressed mouse primase subunits, p49 and p58. Neither of the
      singly purified primase subunits displayed primase activity alone, but the p49
      subunit was able to extend a riboprimer, indicating that this subunit contains an
      RNA polymerase activity. The p58 subunit cooperated with the p49 subunit in
      binding the initiating purine to form the initial dinucleotide. After initiation,
      the p49 subunit alone was sufficient to extend the growing primer, but both the
      rate of p49 primer extension and its stability were influenced by the p58
      subunit. The Km(ATP) in primer synthesis on poly(dT) of the p49-p58 heterodimeric
      primase complex was 10-fold higher than the Km(ATP) of the single p49 subunit in
      a ribo(A) primer extension assay. In addition, labeled ATP cross-linked to both
      of the individually purified subunits but with a striking difference in
      affinities; cross-linking was 11-fold more efficient to the p49 subunit. The
      interaction of the two primase subunits with polymerase alpha was also
      investigated. Immunoprecipitation experiments indicate that only the p58 subunit
      directly contacts the p180 subunit of DNA polymerase alpha. Competition
      experiments in the coupled primase-polymerase assay with a catalytically inactive
      mutant of DNA polymerase alpha and the Klenow fragment suggest that the DNA
      polymerase alpha-primase complex does not dissociate from the primer during the
      transition from RNA to DNA synthesis.

PMID- 8253736
TI  - Biochemical characterization of the multifunctional Ca2+/calmodulin-dependent
      protein kinase type IV expressed in insect cells.
AB  - We have expressed the rat brain Ca2+/calmodulin (CaM)-dependent protein kinase
      type IV in insect cells. The recombinant enzyme is produced as a single
      polypeptide that migrates on SDS-polyacrylamide gel electrophoresis at 61 kDa.
      Recombinant CaM kinase IV undergoes slow CaM-dependent autophosphorylation. The
      autophosphorylation of CaM kinase IV occurs on serine residues but is not
      accompanied by the generation of a CaM-independent activity, as previously
      reported for the cerebellar enzyme. Comparison of peptide and protein
      phosphorylation by the recombinant CaM kinase IV and the cerebellar enzyme showed
      differences in their catalytic activities. The deduced primary sequence of CaM
      kinase IV contained a domain, 315Phe-Asn-Ala-Arg-Arg-Lys-Leu-Lys323, also found
      in the regulatory domain of CaM kinase II alpha (residues 293-300). Truncation of
      CaM kinase IV at Leu313 (at a position analogous to Leu290 in CaM kinase II
      alpha) generated a fully active, CaM-independent enzyme. This truncated enzyme no
      longer bound CaM. These data confirm that CaM kinase IV demonstrates intrasteric
      regulation by an autoinhibitory domain and provides insight into a potentially
      common mechanism for the regulation of the CaM-dependent multifunctional protein
      kinases. A number of synthetic peptides were examined for their phosphorylation
      by both CaM kinase II and IV. These studies showed that several peptides derived
      from phospholamban were preferential substrates for CaM kinase II whereas a
      peptide derived from S6 ribosomal protein was selectively phosphorylated by CaM
      kinase IV. Kinetic analysis of several peptide substrates suggests that while
      both CaM kinase II and IV recognize the sequence motif represented by R-X-X-T/S,
      other structural features are also involved in defining the unique substrate
      specificity of CaM kinase IV.

PMID- 8253738
TI  - Absence of ligand binding-induced tertiary changes in the multimeric earthworm
      Lumbricus terrestris hemoglobin. A resonance Raman study.
AB  - In vertebrate hemoglobins, changes in protein tertiary structure induced by
      either ligand binding or changes in quaternary state are manifested at the heme
      as reflected in resonance Raman spectral changes involving the iron-proximal
      histidine stretching mode. No such changes are observed for Lumbricus terrestris
      hemoglobin. The iron-histidine stretching mode and the porphyrin breathing motion
      in the deoxy-, oxy-, or CO-photodissociated forms of Lumbricus hemoglobin and
      human hemoglobin A (pH 7.0 and 9.2, the latter to effect Lumbricus hemoglobin
      subunit dissociation) were studied using pulsed (10 ns) light at 435 nm. In
      contrast to that observed for hemoglobin A, a comparison of the spectra of the
      deoxy and photoproduct forms of Lumbricus hemoglobin reveal minimal differences
      in the region of the iron-histidine and the pi electron distribution in the heme
      moiety. The spectral frequencies are similar to that observed in R-state
      vertebrate hemoglobins. Such average behavior of the approximately 192 hemes
      present in Lumbricus hemoglobin is more analogous to the Raman spectral
      properties observed in myoglobin.

PMID- 8253739
TI  - Domains that confer intracellular sequestration of the Glut4 glucose transporter
      in Xenopus oocytes.
AB  - The Glut4 glucose transporter is poorly functional compared with other glucose
      transporter isoforms when expressed in Xenopus oocytes. To investigate the
      molecular basis for this poor functionality, we compared the biosynthesis and
      targeting of Glut1 and Glut4 in oocytes after microinjection of the corresponding
      mRNAs. Both Glut1 and Glut4 were present as lower molecular weight
      endoglycosidase H-sensitive and higher molecular weight endoglycosidase H
      resistant. Subcellular fractionation indicated that Glut1 was targeted to the
      plasma membrane with a 6.6-fold greater efficiency than was Glut4. Confocal
      immunofluorescence microscopy confirmed the relative enrichment of Glut1 in the
      plasma membrane and the efficient intracellular sequestration of Glut4. As in
      mammalian cells, the endoglycosidase H-resistant form of Glut4 was concentrated
      in low-density intracellular vesicles, whereas Glut1 was distributed in
      intracellular vesicles of higher average density. The structural basis for the
      differential localization of Glut1 and Glut4 was investigated by determining the
      plasma membrane content of a series of chimeric Glut1/Glut4 molecules. These data
      indicated that two distinct regions of Glut4, encompassing residues 24-132 and
      the COOH-terminal cytoplasmic tail, confer intracellular sequestration on the
      chimeric transporter molecules. At least part of the sequestration effect of the
      more N-terminal domain was due to the incomplete maturation of chimeras
      containing this region, resulting in the accumulation of lower molecular weight
      endoglycosidase H-sensitive and endoglycosidase H-resistant forms, whereas the
      COOH-terminal cytoplasmic tail conferred sequestration of fully glycosylated
      chimeras in a low-density intracellular membrane compartment.

PMID- 8253740
TI  - Role of ribonucleotide reductase in inhibition of mammalian cell growth by potent
      iron chelators.
AB  - Ribonucleotide reductase consists of two nonidentical subunits, proteins R1 and
      R2, the latter of which contains an iron-tyrosyl free radical center essential
      for activity. We have studied the in vivo effects on the R2 protein of the potent
      iron chelators parabactin and desferrioxamine using R2-overproducing mouse cells
      with a tyrosyl free radical signal easily quantifiable by EPR spectroscopy. Both
      chelators inhibited cell growth, and the inhibition was reversible by iron.
      Furthermore, both chelators, which penetrate cells and chelate the intracellular
      iron pool, caused a disappearance of the R2 tyrosyl free radical. In parallel,
      there was an accumulation of apo-R2 protein in the inhibited cells. In vitro
      studies using pure, 59Fe-labeled recombinant mouse R2 protein unexpectedly showed
      that its iron center is labile at physiological temperatures and that iron is
      spontaneously lost from the protein even in the absence of chelators in a
      temperature-dependent process. Our conclusion is that parabactin or
      desferrioxamine inhibits ribonucleotide reduction and cell growth not by directly
      attacking the iron-radical center of the R2 protein, but instead by chelating the
      intracellular iron pool. This prevents the regeneration of the iron-radical
      center both in newly synthesized apo-R2 protein and in apo-R2 protein
      continuously formed from active R2 protein by the loss of iron.

PMID- 8253741
TI  - Biologically active lipids are regulators of Rac.GDI complexation.
AB  - Members of the Rho family of GTP-binding proteins are localized in the cytosol of
      cells by complexation with a protein known as (Rho)GDI. We show by sucrose
      gradient equilibrium sedimentation analysis that all of the Rac protein present
      in human neutrophil cytosol exists as a complex with (Rho)GDI under non
      activating conditions. This interaction can be disrupted in the presence of
      various lipids which have been shown to have biological activity in a variety of
      systems, including NADPH oxidase activation. Particularly effective were
      arachidonic acid, phosphatidic acid, and phosphatidylinositols. These lipids were
      active at concentrations from 0.5-50 microM and were capable of disrupting
      complexation of (Rho)GDI with both GDP- and GTP-bound forms of Rac, although the
      latter were more sensitive to lipid. These data suggest that certain lipids
      generated in chemoattractant-stimulated neutrophils may play a role in modulating
      the activity of Rac and thus NADPH oxidase activity.

PMID- 8253742
TI  - Comparison of calmodulin and troponin C with and without its amino-terminal helix
      (residues 1-11) in the activation of erythrocyte Ca(2+)-ATPase.
AB  - Troponin C can replace calmodulin in the activation of the Ca(2+)-ATPase of pig
      erythrocytes provided that the reaction medium contains relatively high free Ca2+
      concentrations (> 0.5 microM). In the presence of 10 microM free Ca2+, the
      troponin C-activated ATPase reaches a maximal velocity of approximately 70% of
      that attained with calmodulin. The half-maximal concentration for troponin C
      activation is about 200 times greater than for calmodulin. Troponin C displaces
      the half-maximal concentration for activation by Ca2+ to pCa 5.46 and the
      cooperativity between the Ca2+ binding sites to nH 1.1, compared with pCa 6.14
      and nH 1.72 when calmodulin is used. Both EF-hand proteins also elicit activation
      by ATP at a nucleotide regulatory site, as well as a Ca(2+)-dependent p
      nitrophenyl phosphatase activity. Troponin I prevents activation of the enzyme by
      troponin C. A mutant of troponin C with the amino-terminal helix deleted (NHdel)
      activates the Ca(2+)-ATPase to the same extent and with the same Ca2+ dependence
      as wild-type troponin C (rTnC); the half-maximal concentration for activation by
      NHdel is 2.5 times smaller than that for rTnC. We conclude that the structural
      features that distinguish the two EF-hand proteins affect their binding to the
      target enzyme more than their ability to transform the enzyme's response to Ca2+
      or ATP. The differences in the amino-terminal domains of troponin C and
      calmodulin cannot account for the differences in ability of these proteins to
      activate the target system used as a model.

PMID- 8253743
TI  - Selectivity of ceramide-mediated biology. Lack of activity of erythro
      dihydroceramide.
AB  - Ceramide is emerging as a putative second messenger mediating effects of
      extracellular agents on cell growth and differentiation (Okazaki, T., Bielawska,
      A., Bell, R. M., and Hannun, Y. (1990) J. Biol. Chem. 265, 15822-15831) and
      programed cell death (Obeid, L. M., Linardic, C. M., Karolak, L. A., and Hannun,
      Y. A. (1993) Science 259, 1769-1771). In this study, the eight stereoisomers of
      C2-ceramide and dihydroceramide were synthesized, and their cellular activity was
      investigated. The four stereoisomers of C2-ceramide were active in inhibition of
      cell growth and induction of apoptosis with modest differences in potency. On the
      other hand, with C2-dihydroceramide only the threo compounds were active in these
      assays whereas the erythro compounds were totally inactive. Thus, of the two
      naturally occurring molecules, the analog of D-erythro-ceramide (with the 4-5
      trans double bond) was active, whereas the analog of D-erythro-dihydroceramide
      was inactive. These results demonstrate the specificity of ceramide action and
      suggest that the introduction of the double bond is critical for imparting the
      biochemical and biological activity of ceramide.

PMID- 8253744
TI  - A new class of carbonic anhydrase inhibitor.
AB  - Aliphatic sulfonamides, as CH3SO2NH2, are very weak inhibitors of the carbonic
      anhydrases (KI congruent to 10(-4) M) and are extremely weak acids (Ka congruent
      to 10(-10.5) M). We now find CF3SO2NH2 a very potent inhibitor of carbonic
      anhydrase II (KI = 2 x 10(-9) M) and a much stronger acid (Ka = 10(-5.8) M). It
      freely dissolves in water, a 2% solution yielding pH 3.7, the strongest known
      sulfonamide acid. CHCl3/aqueous partition with this solution is very low, 0.006.
      The plot of CH3SO2NH2 and eight hydrophilic halo-alkyl congeners gives a linear
      relation over 5 orders of magnitude, pKI increasing as pKa declines. Transcorneal
      permeability of CF3SO2NH2 in rabbits is very high; from one drop on the cornea it
      rapidly gains access to the ciliary process, where it fully inhibits carbonic
      anhydrase and gives the maximum pressure drop (for any drug) of 6 mm Hg at 30-60
      min. Action is short due to rapid disappearance of free drug from the eye at the
      rate of aqueous humor flow. Analyses are made of binding of CF3SO2NH2 to carbonic
      anhydrase and melanin in ciliary process. CF3SO2NH2 is not attacked by
      glutathione, is 75% bound to plasma protein, and is not taken into the renal
      secretory system. Excretion rate follows from glomerular filtration and tubular
      reabsorption. Intravenous injection thus leads to prolonged plasma levels (half
      life, 24 h), a general diffusion into tissues and alkalinization of the urine, as
      with "classic" inhibitors. Drug is bound to carbonic anhydrase in red cells and
      decays with half-life of 4 days. The rapid and effective binding to carbonic
      anhydrase of this small hydrophilic molecule shows that complex lipophilic
      structures are not necessary for powerful inhibition of the enzyme. It does not
      appear essential for a sulfonamide to occupy a "hydrophobic pocket" in the active
      site cavity to react effectively at the zinc center.

PMID- 8253745
TI  - Calcium channel subtypes controlling serotonin release from human small cell lung
      carcinoma cell lines.
AB  - Small cell lung carcinoma is an aggressive neuroendocrine tumor that secretes
      several hormones, some of which act as autocrine growth factors. In order to
      obtain more information on the process of hormone secretion from this tumor, we
      have studied the role of intracellular free Ca2+ concentrations and voltage
      operated calcium channels in the control of [3H]serotonin release from in vitro
      growing cell lines. We found that the Ca2+ ionophore ionomycin and the Ca(2+)
      ATPase antagonist thapsigargin induced a dose-dependent increase of intracellular
      Ca2+ and a parallel enhancement of [3H]serotonin release. KCl-induced
      depolarization also stimulated a dose- and Ca(2+)-dependent [3H]serotonin release
      that in the GLC8 cell line was effectively inhibited by Ca2+ channel antagonists
      (Cd2+, nitrendipine, verapamil, omega-conotoxin GVIA, and omega-agatoxin IVA) and
      potentiated by the Ca2+ channel agonist BayK8644. Autoantibodies against Ca2+
      channels present in the sera of Lambert-Eaton myasthenic patients antagonized KCl
      but not ionomycin-induced [3H]serotonin release. Polymerase chain reaction
      analysis indicated that GLC8 cells express L-, N-, and P-type neuronal Ca2+
      channel alpha 1 subunits, together with two types of Ca2+ channel beta subunits.
      The presence of three functionally distinct high threshold Ca2+ channels was also
      revealed by patch clamp experiments; high threshold Ca2+ channels were identified
      as dihydropyridine-sensitive (L-type), omega-conotoxin GVIA-sensitive (N-type),
      and omega-agatoxin IVA-sensitive (P-type). Our data demonstrate that
      [3H]serotonin is released by small cell lung carcinoma cells in a Ca(2+)
      dependent manner and that depolarization-induced [3H]serotonin release is
      mediated by Ca2+ influx through distinct, neuron-like, Ca2+ channel subtypes.

PMID- 8253746
TI  - Evidence for stereospecific inositol 1,3,4,5-[3H]tetrakisphosphate binding sites
      on rat liver nuclei. Delineating inositol 1,3,4,5-tetrakisphosphate interaction
      in nuclear calcium signaling process.
AB  - 3H-Labeled inositol 1,3,4,5-tetrakisphosphate (IP4) binding sites are observed on
      nuclei isolated from rat liver and devoid of any microsomal, mitochondrial, or
      plasma membrane constituents. A pH of about 6.5 is found optimum for maximum
      [3H]IP4 specific binding that is sensitive to changes in pH. The [3H]IP4 binding
      on the nuclei can be distinguished into a high affinity site and a low affinity
      site. The two binding sites are characterized by distinct KD and Bmax (1.6 nM
      versus 57.0 nM KD; 0.25 pmol/mg protein and 3.7 pmol/mg protein Bmax). IP4 is
      capable of 45Ca2+ uptake even in the absence of ATP. The calcium uptake by nuclei
      is highly sensitive to IP4 since it is achieved even at 1 nM IP4 concentration.
      Furthermore, data are documented demonstrating that a rapid and transient 45Ca2+
      release by inositol 1,4,5-trisphosphate (IP3) from the intact nuclei can be
      reversed by IP4. The presence of IP3 potentiates the action of IP4 in nuclear
      calcium reuptake as attested by the rate of calcium uptake by IP4 in the absence
      of IP3 (0.16 nmol/s/mg of protein) and in the presence of IP3 (4.0 nmol/s/mg of
      protein). A novel mechanism of nuclear calcium signaling is proposed where IP4
      brings calcium into the nuclei mediated by its specific putative binding sites.

PMID- 8253747
TI  - Solution conformational analysis of the alpha-zein proteins of maize.
AB  - Small angle x-ray scattering and viscometric analyses of the alpha-zeins of maize
      in solution indicated that the molecules were asymmetric. Structure predictions
      of consensus sequences for the two classes of alpha-zeins, Z19 and Z22, were in
      good agreement with the alpha-helical contents determined by circular dichroism.
      Dimensions determined by small angle x-ray scattering and viscometry indicated a
      predominantly alpha-helical conformation. The data are discussed in relation to
      models for the solution conformation and to earlier models for alpha-zeins
      structure.

PMID- 8253748
TI  - The peptidoglycan composition of a Staphylococcus aureus mutant selected for
      reduced methicillin resistance.
AB  - The peptidoglycan of a Tn551 mutant of Staphylococcus aureus (RUSA208) selected
      for reduced methicillin resistance was analyzed by reversed-phase high pressure
      liquid chromatography and mass spectrometry. RUSA208 is a member of a cluster of
      Tn551 mutants located on fragment A of SmaI digests but is distinct from the femA
      and femB class of mutants. The peptidoglycan of RUSA208 contained normal parental
      muropeptides but in diminished amounts only. The major muropeptides of RUSA208
      were new components eluting with somewhat longer retention times from the column.
      Amino acid analysis of these new muropeptides showed identical compositions to
      the corresponding peaks in the parental strain, but mass spectrometry revealed
      increased molecular weights by the following mass units: 1 (in monomers), 1 or 2
      (in dimers), and 2 or 3 (in trimers). These observations suggest that in RUSA208
      the mutational block may be in the amidation of the stem peptide glutamate
      residues, resulting in the replacement of isoglutamine with free glutamic acid in
      one or more of the cell wall stem peptides.

PMID- 8253749
TI  - Purification and characterization of CMP-N-acetylneuraminic acid:lactosylceramide
      (alpha 2-3) sialyltransferase (GM3-synthase) from rat brain.
AB  - CMP-N-acetylneuraminic acid:lactosylceramide (alpha 2-3) sialyltransferase (GM3
      synthase) was purified to homogeneity from a Triton CF-54 extract of young rat
      brain. The enzyme was separated by affinity chromatography on CDP-Sepharose
      column and resolved by linear NaCl gradient elution from the same adsorbent.
      Final purification of GM3-synthase was achieved by chromatography on a
      "lactosylceramide acid"-Sepharose column and specific elution with
      lactosylceramide. The enzyme activity was highest at pH 6.5 and required the
      presence of Triton CF-54 (0.15%) and Mn2+ (10 mM) for its full activity. The
      product of the reaction catalyzed by the enzyme was identified as GM3 based on
      its mobility on thin layer chromatographic plates using two different solvent
      systems. Comparison with several glycolipid substrates showed high specificity of
      GM3-synthase for lactosylceramide. The apparent Km value for lactosylceramide and
      CMP-N-acetylneuraminic acid were 80 and 210 microM, respectively. The apparent
      molecular mass of the enzyme determined on SDS-polyacrylamide gel electrophoresis
      was 76 kDa.

PMID- 8253750
TI  - Antigenicity and immunogenicity of modified synthetic peptides containing D-amino
      acid residues. Antibodies to a D-enantiomer do recognize the parent L-hexapeptide
      and reciprocally.
AB  - The effect of introducing D-amino acid residues in an hexapeptide was examined
      both at the antigenic and immunogenic levels. A series of D-analogues of the
      model peptide of sequence IRGERA corresponding to the COOH-terminal residues 130
      135 of histone H3 were produced. Four analogues contained a single change of an L
      residue by the corresponding enantiomer, one peptide contained two D-residues and
      another one contained only D-residues (D-enantiomer). A peptide analogue was also
      synthesized in which the 2 Arg residues were replaced by Lys residues. The parent
      peptide and peptide analogues were injected into mice after covalent coupling to
      small unilamellar liposomes containing monophosphoryl lipid A as adjuvant. The
      substitution of L-Arg131 to Lys or D-Arg was found to change neither the
      antigenic nor immunogenic properties of the resulting peptides. In contrast, the
      substitution of Glu133, Arg134, and Ala135 by the respective enantiomers
      drastically altered the antigenicity of the modified peptides. Each of the six D
      analogues induced an immune response with an unusually high level of IgG3
      antibodies. The D-enantiomer produced IgG3 antibodies which reacted with the
      homologous peptide as well as with the all L-peptide and the parent protein H3 in
      solution but not with analogues containing one or two D-residues only. IgG3
      antibodies produced against the all L-peptide reacted with the free all D-peptide
      but not with the other analogues containing D-residues in position 133, 134, and
      135.

PMID- 8253751
TI  - Dynamic 13C NMR analysis of oxidative metabolism in the in vivo canine
      myocardium.
AB  - Oxidative metabolism in the in vivo canine myocardium was studied noninvasively
      using 13C-enriched acetate and non-steady state 13C NMR techniques. Under low
      workload conditions, the myocardium oxidized the infused [2-13C]acetate and
      incorporated the labeled carbon into the glutamate pool as expected. This
      conclusion stems from the rapid enrichment of the C-2, C-3, and C-4 carbons of
      glutamic acid both under in vivo conditions and in extracts. Surprisingly, [2
      13C]acetate uptake was not observed at high workloads as reflected by an absence
      of glutamate pool enrichment at these rate pressure products. Rather, the
      myocardium selected its substrate from an endogenous pool. Since free acetate can
      directly cross the inner mitochondrial membrane and be converted to acetyl-CoA
      through acetyl-CoA synthetase, these results support workload-dependent
      regulation of substrate access to the mitochondrial CoASH pool. As such, we
      advance the hypothesis that the selection of substrate for condensation with
      CoASH and subsequent oxidation in the tricarboxylic acid cycle is regulated
      kinetically through the Km values of the appropriate condensation enzymes and
      through the absolute levels of free CoASH in the mitochondria.

PMID- 8253752
TI  - Synthesis and characterization of kaliotoxin. Is the 26-32 sequence essential for
      potassium channel recognition?
AB  - Kaliotoxin (KTX), a scorpion toxin characterized as a 37-residue inhibitor of the
      neuronal high conductance Ca(2+)-activated K+ channels (KCa channels), has been
      chemically synthetized. Differences were observed between natural toxin and the
      two peptides, KTX(1-37) and KTX(1-37)-amide. Re-examination of the KTX sequence
      showed that an extra lysine residue was present at the C-terminal end. The 38
      residue synthetic peptide was found identical with natural toxin. All three
      peptides had comparable activities, with LD50 values of 6-9 pmol/mouse after
      intracerebroventricular injection, and Kd = 2-8 nM for blockage of the whole cell
      and unitary molluscan KCa currents. Pairing of the disulfide bonds in synthetic
      KTX corresponded to that in charybdotoxin and iberiotoxin. A competition assay
      between 125I-KTX(1-37) and different toxins (KTX, dendrotoxin, charybdotoxin, MCD
      peptide, and iberiotoxin) for binding to rat brain synaptosomal membranes
      suggested that KTX interacts also with voltage-gated K+ channels. Shorter
      peptides, KTX(25-35)-amide and KTX(26-32)-amide, expressed no KTX activity, but
      were able to compete in binding. They were further shown to antagonize KTX in
      both its toxicity and blocking activity. The (26-32) sequence of KTX, which is a
      highly conserved region, may contain a low affinity binding subsite essential for
      potassium channel recognition.

PMID- 8253753
TI  - Specific sequences in the signal anchor of the beta-galactoside alpha-2,6
      sialyltransferase are not essential for Golgi localization. Membrane flanking
      sequences may specify Golgi retention.
AB  - The beta-galactoside alpha-2,6-sialyltransferase is a trans Golgi/trans Golgi
      network glycosyltransferase which adds sialic acid residues to Asn-linked
      oligosaccharides of glycoproteins. Previous results suggested that the
      sialyltransferase stem and signal anchor including flanking sequences may be two
      independent Golgi retention regions. However, other experiments demonstrated that
      the sequence of the signal anchor itself was not important. To investigate
      whether the sialyltransferase signal anchor was necessary and sufficient for
      Golgi retention, several mutant and chimeric proteins were expressed and
      localized in Cos-1 and Chinese hamster ovary cells. We found that the signal
      anchor and flanking sequences were able to retain the sialyltransferase catalytic
      domain in the Golgi. However, efficient Golgi retention was still observed when
      the signal anchor was altered or entirely replaced in either the presence or
      absence of most of the luminal stem region. Chimeric proteins consisting of the
      sialyltransferase cytoplasmic tail and signal anchor fused to the extracellular
      domains of two different cell surface proteins demonstrated poor Golgi retention.
      A significant increase in the Golgi retention of one of these chimeras was
      observed when two lysines were placed next to the signal anchor on the luminal
      side. Taken together these results suggest that the sialyltransferase signal
      anchor is not necessary or sufficient for Golgi retention, rather, appropriately
      spaced cytoplasmic and luminal flanking sequences are the important elements of
      the sialyltransferase Golgi retention region.

PMID- 8253754
TI  - Structural features which control folding of homologous proteins in cell-free
      translation systems. The effect of a mitochondrial-targeting presequence on
      aspartate aminotransferase.
AB  - When the precursor to mitochondrial aspartate aminotransferase (pmAspAT) is
      synthesized in a rabbit reticulocyte lysate translation system (RRL), its
      properties are quite unlike those of the purified protein (Mattingly, J.R., Jr.,
      Youssef, J., Iriarte, A., and Martinez-Carrion, M. (1993) J. Biol. Chem. 268,
      3925-3937). These results suggest that molecular chaperones present in RRL
      modulate the folding of pmAspAT. To investigate the structural basis for this, we
      have used protease resistance to monitor the extent of folding for several
      related AspATs after synthesis in RRL and in wheat germ extract (WGE). In
      addition to pmAspAT, the following proteins were examined: the mature form of
      pmAspAT (delta 2-28 pmAspAT), its cytosolic counterpart (cAspAT), a chimeric
      protein consisting of the presequence of pmAspAT attached to the amino terminus
      of cAspAT (pcAspAT), and a pmAspAT variant in which the presequence and the amino
      terminal domain of the mature enzyme are deleted (delta 2-57 pmAspAT). In RRL,
      delta 2-28 pmAspAT folds somewhat faster than intact pmAspAT, whereas the
      truncated delta 2-57 pmAspAT is unable to fold. In contrast, cAspAT and pcAspAT
      both fold with extreme rapidity. After synthesis in WGE, pmAspAT and delta 2-28
      pmAspAT never acquire a protease-resistant conformation, whereas the folding of
      cAspAT and pcAspAT still occurs rapidly. We conclude that the presequence has
      only a minor role in determining the folding rate of the pmAspAT mitochondrial
      precursor protein in RRL or WGE and has no influence on the folding of the
      homologous cAspAT. Rather, the primary sequence of the mature part of the protein
      seems to dictate whether or how molecular chaperones regulate folding events.

PMID- 8253755
TI  - Human major histocompatibility complex class II-associated invariant chain gene
      promoter. Functional analysis and in vivo protein/DNA interactions of
      constitutive and IFN-gamma-induced expression.
AB  - Major histocompatibility complex (MHC) class II-associated invariant chain (Ii)
      gene and the MHC class II molecules are physically and functionally associated
      within class II-expressing cell types. These genes are generally co-expressed in
      various cell types and coordinately induced by cytokines such as interferon-gamma
      (IFN-gamma). Human Ii gene shares a regulatory mechanism with MHC class II genes
      via the X and Y cis-acting elements. Ii X and Y are required for constitutive
      expression in B lymphoid cell lines and for induction by IFN-gamma in a
      glioblastoma cell line. The Servenius element (S) contributes 5-fold
      transcriptional activity to class II gene HLA-DRA, and an S homologue has been
      implied in Ii gene regulation. Now we report that along with X and Y, the Ii S
      box functions in a positive manner to regulate Ii transcription in B cell lines
      but not in T cell lines. In addition, S,X, and Y are all necessary for induced
      expression of Ii in an IFN-gamma-regulated glioblastoma cell line and in primary
      untransformed glial cells. Transcriptional activity of Ii X and Y elements
      correlates with the presence of in vivo protein/DNA interactions in Ii-expressing
      cells. Most interestingly, in vivo interactions are induced upon IFN-gamma
      induction in a time-dependent fashion. Thus, the Ii promoter contains elements
      that coordinately regulate expression with the MHC class II genes, and these
      functional sites are contacted in vivo emphasizing their importance in Ii gene
      transcription.

PMID- 8253756
TI  - Functional expression of the Enterococcus hirae NaH-antiporter in Escherichia
      coli.
AB  - We recently described the cloning of napA, the putative structural gene for the
      NaH-antiporter of Enterococcus hirae (Waser, M., Bienz-Hess, D., Davies, K., and
      Solioz, M. (1992) J. Biol. Chem. 267, 5396-5400). To analyze the gene product of
      napA, we expressed it in Escherichia coli. When placed under the control of a T7
      promoter, napA could be transcribed and labeled specifically with
      [35S]methionine. The resultant gene product exhibited an apparent M(r) of 3,4 x
      10(4) when subjected to sodium dodecyl sulfate-gel electrophoresis. The function
      of NapA was tested by expressing it from its own promoter in the E. coli mutant
      EP432. This mutant lacks both of the endemic NaH-antiporters, NhaA and NhaB; its
      growth is thus very sensitive to Na+ and Li+ and membranes derived from this
      strain do not exhibit NaH-antiport activity. When complemented with napA, EP432
      gained tolerance to Na+ or Li+. Membranes prepared from the complemented mutant
      exhibited NaH-antiport activity. The properties of this activity were determined
      by acridine fluorescence measurements on vesicles energized with lactate. The NaH
      antiporter expressed by napA exhibited a Km of 1 mM for Na+ and 0.1 mM for Li+ at
      pH 7.5. At pH 8.5, the relative rate of NaH-antiport activity was 50%, with
      little change in the Km, and approached zero at pH 9. These results demonstrate
      that napA is the structural gene for the NaH-antiporter of E. hirae. NapA
      exhibits properties different from those of the two E. coli NaH-antiporters
      encoded by nhaA and nhaB, yet functionally complements a defect in these genes.

PMID- 8253757
TI  - Structure of the N-linked oligosaccharides that show the complete loss of alpha
      1,6-polymannose outer chain from och1, och1 mnn1, and och1 mnn1 alg3 mutants of
      Saccharomyces cerevisiae.
AB  - The periplasmic invertase was purified from Saccharomyces cerevisiae och1::LEU2
      disruptant cells (delta och1), which have a defect in elongation of the outer
      chain attached to the N-linked core oligosaccharides (Nakayama, K., Nagasu, T.,
      Shimma, Y., Kuromatsu, J., and Jigami, Y. (1992) EMBO J. 11, 2511-2519).
      Structural analysis of the pyridylaminated (PA) neutral oligosaccharides released
      by hydrazinolysis and N-acetylation confirmed that the och1 mutation causes a
      complete loss of the alpha-1,6-polymannose outer chain, although the PA
      oligosaccharides (Man9GlcNAc2-PA and Man10GlcNAc2-PA), in which one or two alpha
      1,3-linked mannose(s) attached to the endoplasmic reticulumn (ER)-form core
      oligosaccharide (Man8GlcNAc2) were also detected. Analysis of the delta och1 mnn1
      strain oligosaccharides released from total cell mannoprotein revealed that the
      delta och1 mnn1 mutant eliminates the alpha-1,3-mannose attached to the core and
      accumulates predominantly a single ER-form oligosaccharide species (Man8GlcNAc2),
      suggesting a potential use of this strain as a host cell to produce glycoproteins
      containing mammalian high mannose type oligosaccharides. The delta och1 mnn1 alg3
      mutants accumulated Man5GlcNAc2 and Man8GlcNAc2 in total cell mannoprotein,
      confirming the lack of outer chain addition to the incomplete corelike
      oligosaccharide and the leaky phenotype of the alg3 mutation. All the results
      suggest that the OCH1 gene encodes an alpha-1,6-mannosyltransferase that is
      functional in the initiation of alpha-1,6-polymannose outer chain addition to the
      N-linked core oligosaccharide (Man5GlcNAc2 and Man8GlcNAc2) in yeast.

PMID- 8253759
TI  - Human tumor necrosis factor alpha (TNF alpha) mutants with exclusive specificity
      for the 55-kDa or 75-kDa TNF receptors.
AB  - To probe the ligand receptor interface, a number of point mutations were
      introduced in selected regions of human tumor necrosis factor (TNF) alpha by site
      directed mutagenesis. The mutated proteins were expressed in Escherichia coli and
      analyzed for selective binding to recombinant 55- and 75-kDa TNF receptors in
      competition with radiolabeled wild-type TNF alpha. Generally, mutations in the
      loop from position 29 to 34 and at positions 86 and 146 preferentially impaired
      binding to the 75-kDa TNF receptor, whereas mutations in the region from 143 to
      145 mainly affected binding to the 55-kDa TNF receptor. Mutation of the conserved
      Tyr87 resulted in a dramatic loss of binding activity to both receptors. The
      selectivity for one or the other receptor type was found to be enhanced by
      combining two or three point mutations, the effects of the single mutations with
      respect to receptor selectivity being at least additive. A combination of the
      mutations Arg32-->Trp and Ser86-->Thr yielded a double mutant (R32W-S86T) with
      wild-type binding to the 55 kDa, but no measurable binding to the 75-kDa TNF
      receptor. In contrast, combining the Asp143-->Asn and Ala145-->Arg mutations
      (D143N-A145R) resulted in a complete loss of binding to the 55-kDa TNF receptor,
      whereas binding to the 75-kDa TNF receptor was impaired by only 5-10-fold. In
      functional assays, selective activation of the 55-kDa TNF receptor by the R32W
      S86T mutant elicited a full cytotoxic response in human KYM-1 cells and secretion
      of interleukin 6 and granulocyte-macrophate colony-stimulating factor in human
      umbilical vein endothelial cells. In contrast, stimulation of the 75-kDa TNF
      receptor with the D143N-A145R mutant as well as with agonistic antibodies failed
      to induce these responses.

PMID- 8253758
TI  - Transplasma membrane redox system of HL-60 cells is controlled by cAMP.
AB  - Transplasma membrane redox activity of HL-60 cells was determined by measuring
      the prevention of ascorbate chemical oxidation. The ascorbate free radical
      produced as the first step of ascorbate oxidation was reduced back by the
      transplasma membrane electron transport system, causing then the regeneration of
      extracellular ascorbate. Agents that increase intracellular cAMP, such as
      forskolin and dibutyryl cAMP (db-cAMP), increased the rate of ascorbate
      regeneration by HL-60 cells. Also, the phosphodiesterase-resistant cAMP analogue
      Sp-cAMP-S (agonist of the protein kinase A) increased the electron flow to the
      ascorbate free radical at the plasma membrane. Rp-cAMP-S, antagonist of the
      protein kinase A, partially inhibited the redox activity of cells and abolished
      the effect of Sp-cAMP-S. Inhibition obtained after preincubation of cells in Rp
      cAMP-S was reversed by Sp-cAMP-S. Tunicamycin, a compound that inhibited the
      electron flow to the ascorbate free radical at the plasma membrane, also reduced
      the response of transplasma membrane redox system to Sp-cAMP-S. Lactate slightly
      affected the ascorbate regeneration in nonstimulated cells, but showed a
      significant effect on Sp-cAMP-S-stimulated plasma membrane electron flow. We show
      here a role for cAMP in the short-term modulation of transplasma membrane redox
      system measured as the regeneration of ascorbate at the cell surface of HL-60
      cells, probably mediated by cAMP-dependent protein kinases.

PMID- 8253760
TI  - Enhancement by phosphodiesterase subunits of the rate of GTP hydrolysis by
      transducin in bovine retinal rods. Essential role of the phosphodiesterase
      catalytic core.
AB  - Phosphodiesterase (PDE) in bovine retinal rod outer segments is activated when it
      forms a membrane-bound complex with the alpha-subunit of transducin loaded with
      GTP (T alpha*). At maximal activation, this complex contains two T alpha* and all
      the subunits of native PDE (PDE alpha, PDE beta, and two inhibitory PDE gamma).
      We observed previously (Pages, F., Deterre, P., and Pfister, C. (1992) J. Biol.
      Chem. 267, 22018-22021) that the rate of GTP hydrolysis by transducin in a rod
      outer segment suspension is enhanced when T alpha* is bound to native PDE (PDE
      alpha beta gamma 2). In this article, we compare the effects of PDE species with
      different PDE gamma contents. We show that T alpha* hydrolyzes its GTP faster not
      only when bound to PDE alpha beta gamma 2, but also when bound to PDE alpha beta
      gamma or PDE alpha beta. Moreover, trypsin-treated PDE (PDE gamma-deprived
      soluble PDE) also induces an acceleration of GTP hydrolysis. On the contrary,
      addition of isolated PDE gamma alone does not accelerate GTP hydrolysis. The
      interaction between T alpha* and PDE gamma, which is essential for the activation
      of PDE by T alpha*, is apparently not responsible of the feedback of PDE on T
      alpha*. The interaction of primary importance for the acceleration of GTP
      hydrolysis would be that existing between T alpha* and PDE alpha beta.

PMID- 8253761
TI  - Structures of glycosylphosphatidylinositol membrane anchors from Saccharomyces
      cerevisiae.
AB  - Metabolic labeling studies suggest that Saccharomyces cerevisiae contains many
      glycoproteins that are anchored in the lipid bilayer by
      glycosylphosphatidylinositol membrane anchors. Membrane anchors were purified
      from a crude yeast membrane protein fraction and analyzed by two-dimensional 1H
      1H NMR, fast atom bombardment-mass spectrometry, compositional and methylation
      linkage analyses, as well as chemical and enzymatic modifications. The yeast
      glycosylphosphatidylinositol anchors consist of the following structures:
      ethanolamine-PO4-6(R-2)Man alpha 1-2Man alpha 1-6Man alpha 1-4Glc-NH2 alpha 1
      6myo-inositol-1-PO4-lipid, where R is mainly Man alpha 1- (80%) with some Man
      alpha 1-2Man alpha 1- (15%) and Man alpha 1-3Man alpha 1- (5%). The core region
      of the yeast anchors (ethanolamine-PO4-6Man alpha 1-2Man alpha 1-6Man alpha 1
      4GlcNH2 alpha 1-6myo-inositol-1-PO4) is identical to the conserved core region
      found in glycosylphosphatidylinositol anchors from protozoa and mammals. The
      lipid moieties of the total yeast glycosylphosphatidylinositol anchors are mainly
      ceramides, consisting mostly of C18:0 phytosphingosine and C26:0 fatty acid.
      However, the lipid moiety of the glycosylphosphatidylinositol anchor of the
      purified ggp125 protein is a lyso- or diacylglycerol, containing C26:0 fatty
      acids. This suggests that yeast adds different lipid components to the
      glycosylphosphatidylinositol anchors of different proteins.

PMID- 8253762
TI  - Escherichia coli-derived rat intestinal fatty acid binding protein with bound
      myristate at 1.5 A resolution and I-FABPArg106-->Gln with bound oleate at 1.74 A
      resolution.
AB  - Rat intestinal fatty acid binding protein (I-FABP) is a 131-residue protein
      composed of two short alpha-helices (alpha I and alpha II) and 10 anti-parallel
      beta-strands organized into two nearly orthogonal beta-sheets. The structure of
      crystalline I-FABP with bound tetradecanoate (myristate) has been refined to a
      resolution of 1.5 A and compared to the 1.2 A structure of apo-I-FABP, the 1.9 A
      structure of I-FABP:hexadecanoate (palmitate) and the 1.75 A structure of I
      FABP:9Z-octadecanoate (oleate) to determine how this model fatty acid receptor
      accommodates changes in the length of its fatty acid ligand. Myristate is located
      in the interior of the protein. A highly ordered, electrostatic network
      containing 7 hydrogen (H)-bonds links the OE1 and OE2 atoms of myristate's
      carboxylate group, the indole nitrogen of Trp82, NH1, and NH2 of Arg106, NE2, and
      OE1 of Gln115, and 2 interior ordered waters. The hydrocarbon chain of the bound
      fatty acid is slightly bent. Its convex face lies in a crevice, forming van der
      Waals contacts with the side chains of several hydrophobic and aromatic residues.
      Its concave face is exposed to an array of 8 interior ordered waters whose
      positions are stabilized by H-bond interactions with other waters, H-bond
      interactions with the side chains of polar/ionizable residues, and van der Waals
      contacts with the surface of the fatty acid. Addition of 2 or 4 methylenes to
      myristate produces remarkably little change in the positions of I-FABP's main
      chain and side chain atoms and interior ordered waters. The principal alterations
      are in the conformation of a surface opening (portal) connecting external and
      internal solvent and in the position of the benzene side chain of Phe55. Changes
      in the conformation of the portal reflect movement of two of its components: the
      backbone of alpha II and a type I turn (Ala73, Asp74) connecting two beta
      strands. The positions of the main chain atoms of Ala73 and Asp74 appear to be
      determined by their ability to form van der Waals contacts with the omega
      terminus of the fatty acid. The side chain of Phe55 appears to function as an
      adjustable aromatic lid, located over the portal, whose position is dependent on
      an ability to form van der Waals contacts with a fatty acid's omega
      terminus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8253763
TI  - A single C2 domain from synaptotagmin I is sufficient for high affinity
      Ca2+/phospholipid binding.
AB  - Synaptotagmin I is a Ca(2+)- and phospholipid-binding protein of synaptic
      vesicles with an essential function in neurotransmission. Ca2+/phospholipid
      binding by synaptotagmin I may be mediated by its C2 domains, sequence motifs
      that have been implicated in the Ca2+ regulation of a variety of proteins.
      However, it is currently unknown if C2 domains are sufficient for
      Ca2+/phospholipid binding or if they even directly participate in
      Ca2+/phospholipid binding. In order to address this question, we have studied the
      Ca2+/phospholipid-binding properties of the first C2 domain of synaptotagmin I.
      Our results show that this C2 domain by itself binds Ca2+ and phospholipids with
      high affinity (half-maximal binding at 4-6 microM free Ca2+) and exhibits strong
      positive cooperativity. The C2 domain is specific for negatively charged
      phospholipids and for those divalent cations that are known to stimulate synaptic
      vesicle exocytosis (Ca2+ > Sr2+, Ba2+ >>> Mg2+). These studies establish that C2
      domains can serve as independently folding Ca2+/phospholipid-binding domains.
      Furthermore, the cation specificity and the cooperativity of Ca2+ binding by the
      C2 domain from synaptotagmin I support a role for this protein in mediating the
      Ca2+ signal in neurotransmitter release.

PMID- 8253764
TI  - Purification and characterization of the Saccharomyces cerevisiae RAD1/RAD10
      endonuclease.
AB  - The Saccharomyces cerevisiae RAD1 and RAD10 genes are required for the incision
      step of excision repair, and in addition, they function in mitotic recombination.
      The RAD1 and RAD10 proteins are associated in a tight complex, and genetic
      studies have indicated that complex formation is essential for the RAD1/RAD10
      controlled biological activities. We had previously purified the RAD10 protein to
      near homogeneity from yeast and shown that it is a DNA-binding protein with a
      strong preference for single-stranded DNA. In this study, we purify the RAD1
      protein to near homogeneity from yeast and show that it also binds single
      stranded DNA preferentially and that the RAD1/RAD10 complex possesses an
      endonuclease activity. We characterize the RAD1/RAD10 endonuclease activity on
      both single-stranded and double-stranded DNAs, using agarose gel electrophoresis
      and trichloroacetic acid precipitation. The RAD1/RAD10 nuclease exhibits a much
      higher level of activity on single-stranded DNA than double-stranded DNA. The
      susceptibility of double-stranded DNA to nicking by the RAD1/RAD10 enzyme is
      markedly dependent on the degree of negative superhelicity, such that a 15-fold
      increase in nicking rate is observed from superhelical state sigma = zero to
      sigma = -0.08. The enzyme produces 3'-hydroxyl and 5'-phosphate termini on both
      single- and double-stranded DNAs. We discuss the role of RAD1/RAD10 endonuclease
      in nucleotide excision repair and in mitotic recombination.

PMID- 8253765
TI  - A novel regulatory element associated with age-dependent expression of the rat
      androgen receptor gene.
AB  - A large body of evidence indicates that the genetic program of aging has co
      evolved with the sexual mode of reproduction (Partridge, L., and Barton, N. H.
      (1993) Nature 362, 305-311). Age-dependent changes in target cell sensitivity to
      reproductive hormones can be considered part of this evolutionary linkage. Here
      we describe a novel regulatory element in the rat androgen receptor (AR) gene
      promoter associated with its age-dependent expression in the liver. This element
      consists of two (19 and 25 base pairs) contiguous sites, one specifically binding
      an Age-dependent Factor (ADF) and the other an Associated Factor (AF). Both
      deletion and point mutations of the ADF site result in about a 5-fold decline in
      the AR promoter function. Unlike AF, which is relatively tissue specific, ADF
      appears to be ubiquitous. The ubiquitous and evolutionarily conserved nature of
      ADF suggests a fundamental role of this novel transcription factor in programmed
      gene expression.

PMID- 8253766
TI  - Activation of phosphatidylinositol-3-kinase by platelet-derived growth factor and
      insulin-like growth factor-1 is inhibited by a transmembrane phosphotyrosine
      phosphatase.
AB  - Expression of the transmembrane phosphotyrosine phosphatase (PTPase) CD45 has
      been shown to inhibit hormone-dependent tyrosine phosphorylation and mitogenesis
      (Mooney, R. A., Freund, G. G., Way, B. A., and Bordwell, K. L. (1992) J. Biol.
      Chem. 267, 23443-23446). Here the impact of PTPase expression on insulin-like
      growth factor-1 (IGF-1) and platelet-derived growth factor- (PDGF) dependent
      activation of PI-3-K was investigated. In PTPase+ cells, IGF-1 and PDGF-dependent
      PI-3-K activity in antiphosphotyrosine immunoprecipitates was decreased by 62 +/-
      13 and 46 +/- 17%, respectively, compared to control cells. Similar decreases in
      PI-3-K activity associated with anti-PDGF receptor and anti-insulin receptor
      substrate-1 (IRS-1) immunoprecipitates were also observed. Association of PI-3-K
      with the hormone-activated PDGF receptor decreased approximately 55%, paralleling
      its loss of activation in PTPase+ cells. Tyrosine phosphorylation of the 85-kDa
      subunit of PI-3-K was also inhibited. Similarly, IGF-1 dependent tyrosine
      phosphorylation of IRS-1 was decreased by 45%, and its association with PI-3-K
      was decreased by 65% in PTPase+ cells. Finally, PDGF-dependent tyrosine
      phosphorylation of phospholipase C-gamma 1 and GTPase-activating protein was
      reduced by 60-70% in the PTPase+ cells as was tyrosine phosphorylation of the
      PDGF receptor associated with these proteins. In summary, expression of a
      transmembrane PTPase decreased hormone-dependent PI-3-K activation, tyrosine
      phosphorylation of receptor substrates, and their association with signaling
      complexes. These data support a role for transmembrane PTPases in the regulation
      of receptor signal transduction pathways.

PMID- 8253767
TI  - Soluble CuA-binding domain from the Paracoccus cytochrome c oxidase.
AB  - In cytochrome c oxidase the C-terminal part of subunit II is outside the membrane
      and contains a copper center called CuA. We have expressed this domain of the
      Paracoccus denitrificans oxidase in a soluble form. Data obtained by quantitative
      copper-to-protein measurements, electrospray mass spectrometry, and electron
      paramagnetic resonance spectroscopy show that the center contains two copper
      atoms probably in a mixed valence configuration. Its absorbance spectrum is
      similar to that of the copper center A in nitrous oxide reductase. The EPR
      spectrum suggests that the center in the soluble protein is closely related to
      the native CuA site in the cytochrome oxidase complex. However, it seems likely
      that the copper center in the soluble domain is more exposed to the aqueous
      milieu than in the intact complex because its absorbance and EPR spectra are
      sensitive to pH. At alkaline pH one of the coppers in the site acquires type-2
      character, indicating that it may be coordinated to a new ligand. The pK of this
      reversible change is about 8.2. The CuA-binding fragment is able to oxidize
      cytochrome c.

PMID- 8253768
TI  - Mitogen-activated protein kinase activation is not sufficient for stimulation of
      glucose transport or glycogen synthase in 3T3-L1 adipocytes.
AB  - The role of mitogen-activated protein (MAP) kinase in the regulation of glucose
      metabolism has been investigated by comparing the effects of insulin and
      epidermal growth factor (EGF) on MAP kinase activation, glucose transport, and
      glycogen synthase in 3T3-L1 adipocytes. Insulin or EGF treatment for 5 min
      increased p42mapk and p44mapk activity to the same extent as determined by myelin
      basic protein kinase activity measurements and phosphotyrosine immunoblotting.
      The profiles of myelin basic protein kinase activity following MonoQ
      chromatography of extracts obtained from cells incubated with insulin or EGF were
      almost identical. Insulin increased glucose transport and GLUT4 translocation to
      the cell surface by 15- and 7-fold, respectively. EGF had no significant effect
      on these processes. Insulin increased the glycogen synthase ratio (-Glc-6-P/+Glc
      6-P) by 7.5- and 3.5-fold in the presence and absence of glucose, respectively.
      EGF increased the ratios by only 2- and 1.3-fold, respectively. EGF did not
      appear to inhibit downstream of MAP kinase, because when adipocytes were
      incubated with insulin plus EGF, the stimulation of glucose transport and
      glycogen synthase was similar to that observed with insulin alone. These findings
      indicate that activation of the MAP kinase isoforms p42mapk and p44mapk is not
      sufficient for the activation of glucose transport and glycogen synthase in 3T3
      L1 adipocytes.

PMID- 8253769
TI  - Proteolytic release of human angiotensin-converting enzyme. Localization of the
      cleavage site.
AB  - Angiotensin-converting enzyme (EC 3.4.15.1, ACE) is a transmembrane protein with
      a short carboxyl-terminal cytoplasmic domain, a 17-amino acid hydrophobic anchor
      domain, and a large N-terminal extracellular region containing two catalytically
      homologous domains. An active soluble form of ACE circulates in human plasma and
      is produced in culture medium of Chinese hamster ovary (CHO) cells transfected
      with the full-length human ACE cDNA. The mechanism of ACE release in CHO cells
      involves a post-translational proteolytic cleavage occurring in the carboxyl
      terminal region. The carboxyl terminus of the secreted recombinant ACE, AGQR, was
      established by carboxyl-terminal microsequencing and corresponds to a cleavage
      site between Arg-1137 and Leu-1138. Two independent studies confirmed this
      proposed cleavage site: amino acid analysis of a carboxyl-terminal peptide
      derived from soluble ACE and immunocharacterization of membrane-bound and soluble
      ACE with antibodies raised against three peptides located along the carboxyl
      terminal ACE sequence. In order to assess the importance of Arg-1137, this amino
      acid was mutated to a glutamine residue. This mutation did not prevent the
      secretion of ACE, suggesting that the solubilizing enzyme can accommodate this
      change or can use an alternative cleavage site. Finally, the production of
      soluble ACE in CHO cells appears to be proportional to the level of cellular ACE,
      implying that the solubilizing enzyme is not a limiting factor. In addition, the
      carboxyl-terminal sequence of the human plasma ACE was identified as AGQR, thus
      supporting the fact that a similar mechanism could operate in human vascular
      cells.

PMID- 8253770
TI  - Molecular cloning and expression of cDNA encoding rat skeletal muscle cytosolic
      sialidase.
AB  - We have isolated a cDNA clone encoding the cytosolic sialidase of rat skeletal
      muscle. Degenerate oligonucleotides, based on amino acid sequence data for the
      purified enzyme, were used as primers to amplify fragments of the gene from rat
      skeletal muscle cDNA by the polymerase chain reaction. The amplified cDNA
      fragment was then applied as probe to screen a rat skeletal muscle cDNA library.
      The longest cDNA clone thus isolated was incomplete at the 5'-end, and therefore
      an amplified cDNA from the 5'-end portion of the gene was further generated by
      polymerase chain reaction. These two cDNAs were used to construct a cDNA encoding
      the entire sequence of rat sialidase. The composite sequence encodes an open
      reading frame of 379 amino acids that include all sequenced peptides. Although
      the deduced amino acid sequence is not largely similar to those of bacterial and
      parasite sialidases, it contains two Asp blocks, the conserved sequence of the
      sialidases from these microorganisms. When the cDNA was inserted into an
      expression vector followed by transformation in Escherichia coli, sialidase
      activity appeared in the cell extract. The sialidase could be completely
      immunoprecipitated by antiserum against the cytosolic sialidase of rat skeletal
      muscle.

PMID- 8253771
TI  - Expression of human tyrosine kinase-negative epidermal growth factor receptor
      amplifies signaling through endogenous murine epidermal growth factor receptor.
AB  - Recent findings have suggested that certain ligand-dependent responses to EGF may
      be propagated in a manner that is not dependent on the intrinsic tyrosine kinase
      activity of the epidermal growth factor receptor (EGF-R, Campos-Gonzalez, R., and
      Glenney, J. R., Jr. (1992) J. Biol. Chem. 267, 14535-14538) or, alternatively,
      that these responses may occur through the interaction of the human tyrosine
      kinase-deficient EGF-R with an as yet unidentified kinase (Selva, E., Raden, D.
      L., and Davis, R. J. (1993) J. Biol. Chem. 268, 2250-2254). These conclusions
      represent a significant departure from our current understanding of signal
      transduction by receptor tyrosine kinases. Therefore we examined the effect of
      expression of tyrosine kinase-negative human EGF receptor in murine NIH-3T3-2.2
      cells on the EGF-dependent phosphorylation of mitogen-activated protein (MAP-2)
      kinase. In parental cells (NIH-3T3-2.2) that express low levels of endogenous
      murine EGF-R, there was no demonstrable EGF-dependent coupling to MAP-2 kinase.
      In NIH-3T3-2.2 cells transfected with tyrosine kinase-negative human EGF-R, there
      was unexpected EGF-dependent phosphorylation of MAP-2 kinase. Analysis of the
      tyrosine kinase-negative human EGF-R in these cells revealed significant tyrosine
      phosphorylation of the EGF-R. A low level of endogenous murine EGF-R present in
      these cells were also phosphorylated on tyrosine residues and displayed
      autokinase activity. Similar results were obtained using an unrelated cell line
      (B82L cells), in which EGF-dependent phosphorylation of MAP-2 kinase was
      previously attributed to signal propagation through a tyrosine kinase-negative
      human EGF-R (Campos-Gonzalez, R., and Glenney, J. R., Jr. (1992) J. Biol. Chem.
      267, 14535-14538). Taken together, these results suggest that the tyrosine kinase
      negative human EGF-R are able to amplify the response to activation of low levels
      of endogenous murine EGF-R, thus leading to EGF-dependent phosphorylation of MAP
      2 kinase in cells expressing tyrosine kinase-negative human EGF-R.

PMID- 8253772
TI  - Purification and partial amino acid sequence of a mu opioid receptor from rat
      brain.
AB  - A rat brain opioid receptor protein was isolated by binding [epsilon-biotinyl
      Lys32] beta-endorphin to membranes, solubilizing the receptor-ligand (R.L)
      complex with deoxycholate-lysophosphatidylcholine and purifying on immobilized
      streptavidin and wheat germ agglutinin. The purified glycoprotein had a molecular
      mass of 60-70 kDa. Recovery of this protein was blocked by the nonselective
      opioid antagonist naloxone and the highly mu-selective agonist [D-Ala2,N-methyl
      Phe4,Glyol5]-enkephalin but not by the highly delta-selective agonist [D-Pen2,4'
      Cl-Phe4,D-Pen5]enkephalin when these compounds were added as competitors at the
      binding step. The 60-70-kDa receptor protein co-purified through the streptavidin
      column with 40-kDa protein recognized by anti-Gi alpha antibodies. GTP and Na+
      influenced dissociation of the solubilized R.125I-L complex and elution of the
      receptor and G protein from streptavidin in fashions consistent with the
      pharmacology of mu-opioid receptors. A 23-amino acid residue sequence from the
      purified receptor differs at 4 positions from a similar sequence in the murine
      delta-opioid receptor and is encoded within a novel rat brain cDNA isolated by
      polymerase chain reaction with oligonucleotide primers related to the murine
      delta-opioid receptor gene.

PMID- 8253773
TI  - Molecular cloning of the cDNAs for the subunits of rat mitochondrial fatty acid
      beta-oxidation multienzyme complex. Structural and functional relationships to
      other mitochondrial and peroxisomal beta-oxidation enzymes.
AB  - Rat liver mitochondrial fatty acid oxidation multienzyme complex consists of 4
      mol of the alpha-subunit and 4 mol of the beta-subunit, and has three enzyme
      activities of long chain enoyl-CoA hydratase, long chain 3-hydroxyacyl-CoA
      dehydrogenase, and long chain 3-ketoacyl-CoA thiolase. The following cDNA clones
      for the rat enzyme complex were isolated, sequenced, and expressed: 1) the 2,789
      base pair (bp) cDNA clone had a 2,289-bp open reading frame encoding a 82,511-Da
      precursor and a 78,637-Da mature subunit. The deduced amino acid sequence of this
      subunit revealed that this cDNA encodes the alpha-subunit and had regions similar
      to the structure of rat mitochondrial enoyl-CoA hydratase and rat mitochondrial
      enoyl-CoA isomerase on the amino-terminal side, and a part similar to that of pig
      mitochondrial 3-hydroxyacyl-CoA dehydrogenase on the carboxyl-terminal side.
      Expression of this cDNA in COS-1 cells yielded a protein with long chain enoyl
      CoA hydratase and long chain 3-hydroxyacyl-CoA dehydrogenase activities. 2) The
      1,943-bp cDNA clone had a 1,425-bp open reading frame encoding a 51,413-Da
      precursor and a 47,583-Da mature subunit. A high similarity of the structure to 3
      ketoacyl-CoA thiolases and acetoacetyl-CoA thiolases from various sources
      suggests that this clone encodes the beta-subunits. Expression of this cDNA in
      COS-1 cells yielded a protein with long chain 3-ketoacyl-CoA thiolase activity.
      By phylogenetic analysis of the deduced amino acid sequences of the alpha- and
      beta-subunits with those of other beta-oxidation enzymes, it was suggested that
      the alpha-subunit is a descendant of short chain enoyl-CoA hydratase and short
      chain 3-hydroxyacyl-CoA dehydrogenase while the beta-subunit first diverged from
      a common ancestor gene of the thiolase family.

PMID- 8253774
TI  - Evidence for involvement of furin in cleavage and activation of diphtheria toxin.
AB  - Proteolytic cleavage (nicking) of diphtheria toxin (DT) in the 14-amino acid loop
      subtended by the disulfide bond between Cys186 and Cys201 is required for the
      cytotoxic action of DT. The loop includes the consensus motif for cleavage by a
      membrane-anchored protease, furin. We found that a soluble form of furin cleaves
      intact DT between Arg103 and Ser194 in vitro. LoVo cells, a human colon carcinoma
      cell line, do not produce functional furin. We show here that intact DT is not
      cleaved by LoVo cells. The cells are resistant to intact DT, although they are
      sensitive to DT nicked by furin before it is added to the medium. When intact DT
      is added to LoVo/Fur1 cells, a stable transfectant of LoVo cells expressing mouse
      furin, nicked DT associated with the cells is observed. LoVo/Fur1 cells are
      sensitive to both intact and nicked DT. These results indicate that furin is
      involved in the toxicity of intact DT. Bafilomycin A1, an inhibitor of
      intracellular vesicle acidification, did not inhibit cleavage of intact DT by
      LoVo/Fur1 or Vero cells, indicating that cleavage can proceed in a neutral
      environment. Inhibitors of endocytosis decreased DT cleavage but did not
      eliminate it. We also found a small amount of nicked DT in the culture medium.
      These results may indicate that intact DT is cleaved age by cell-associated furin
      on the cell surface as well as in endocytotic vesicles.

PMID- 8253775
TI  - An early response of an AP1-junD complex during T-cell activation.
AB  - Activated T-cell extracts contain an activity (T-AP1) composed of at least two
      dissociable protein components which bind to the AP1 consensus sequence in the
      enhancer of the gibbon ape leukemia virus (GALV)-LTR (GALV-TRE). This activity is
      inducible by 12-O-tetradecanoyl-phorbol-14-acetate (TPA) even in the presence of
      protein synthesis inhibitors. Although one component of this complex (CORE) is
      related immunologically and biochemically to junD, it nevertheless displays
      significant biochemical properties which distinguish CORE from recombinant junD.
      The second component of the complex, flowthrough, interacts more efficiently with
      CORE than with recombinant junD. GALV-TRE enhancer activity is increased within 2
      h in vivo with T cells treated with TPA in the presence of protein synthesis
      inhibitors; this increase in enhancer activity is paralleled by the increased
      GALV-TRE-mediated transcriptional activity present in extracts of these cells.
      Purified T-cell junD activates GALV-TRE-driven RNA synthesis in vitro. The
      rapidity and the protein synthesis-independent nature of TPA-induced T-AP1
      activation suggests that this complex is involved in the earliest stages of T
      cell activation.

PMID- 8253776
TI  - Human X-linked phosphoribosylpyrophosphate synthetase superactivity is associated
      with distinct point mutations in the PRPS1 gene.
AB  - Superactivity of phosphoribosylpyrophosphate synthetase (PRS) is an X chromosome
      linked disorder of purine metabolism, characterized by gout with uric acid
      overproduction and, in some families, neurodevelopmental impairment. Two highly
      homologous isoforms of PRS (PRS1 and PRS2), each encoded by a distinct X
      chromosome-linked locus, have been identified, and PRS1 and 2 cDNAs have been
      cloned. The entire 954-base pair translated regions of PRS1 and 2 cDNAs derived
      from cultured lymphoblasts and fibroblasts from two patients in whom purine
      nucleotide feedback resistance of PRS is associated with enzyme superactivity and
      neurodevelopmental defects were examined by direct sequencing after polymerase
      chain reaction amplification of PRS transcripts. Nucleotide sequences of PRS2
      cDNAs from the patients and normal individuals were identical. In contrast, PRS1
      cDNAs from the patients differ from normal PRS1 cDNA, each by a single base
      substitution. PRS1 cDNA from patient N. B. showed an A to G transition at
      nucleotide 341, corresponding to an asparagine to serine change at amino acid
      residue 113 of mature PRS1. A G to C transversion at nucleotide 547, indicating
      an aspartic acid to histidine change at amino acid 182, was found for PRS1 cDNA
      from patient S. M. Point mutations at the sites identified in the PRS1 cDNAs of
      the two patients were confirmed by the results of RNase mapping analysis. Normal,
      N. B., and S. M. PRS1 cDNAs were introduced into Escherichia coli BL21
      (DE3)/pLyS, and recombinant N. B. and S. M. PRS1s showed the purine nucleotide
      feedback resistance phenotypes characteristic of PRS from patients' cells.

PMID- 8253777
TI  - The transcription of a mammalian voltage-gated potassium channel is regulated by
      cAMP in a cell-specific manner.
AB  - The transcript of Kv1.5, a Shaker-like delayed rectifier K+ channel cloned in our
      laboratory, is regulated in both tissue and developmentally specific manners. In
      this study we characterized the 5'-flanking region of the Kv1.5 gene. The gene
      lacks a canonical TATA box, has several transcription start sites, and the 5'
      noncoding sequence is intronless. A cAMP response element (CRE) consensus signal
      was identified in the 5'-noncoding region. cAMP regulates the expression of Kv1.5
      gene in a cell-specific manner. In primary cardiac cells, cAMP induces a 6-fold
      increase in the steady state levels of Kv1.5 transcript. However, in GH3 cells
      cAMP induces a 5-6-fold decrease in steady state levels of Kv1.5 transcript. The
      half-life of Kv1.5 transcript is 37 min and is not affected by cAMP. Nuclear run
      on experiments show that in GH3 cells, cAMP reduces the transcription rate of
      Kv1.5 gene. Transient transfection assays using 5'-deletion mutations of Kv1.5 5'
      flanking sequences revealed that the CRE located at +636 can confer the cAMP
      inducibility to Kv1.5 reporter gene constructs and binds to CRE-binding protein
      (CREB) and CRE modulator protein (CREM) in electromobility gel shift assays.
      Furthermore, KCl-induced depolarization can increase the steady state levels of
      Kv1.5 transcript in primary atrial cells and decrease it in GH3 cells. We
      conclude that cAMP and depolarization play an important role in regulating K+
      channel expression and thus may induce long term effects on the pattern of
      electrical activity of excitable cells.

PMID- 8253778
TI  - The 5'-flanking region of the rat synapsin I gene directs neuron-specific and
      developmentally regulated reporter gene expression in transgenic mice.
AB  - The expression of the synapsin I gene is neuron-specific and developmentally
      regulated. As a step toward characterizing the molecular mechanisms that are
      responsible for its transcriptional regulation in vivo, we have generated
      transgenic mice that carry the chloramphenicol acetyltransferase (CAT) receptor
      gene under the control of approximately 4,300 nucleotides of 5'-flanking sequence
      of the rat synapsin I gene. In four independent transgenic mouse lines, high
      level CAT expression is observed specifically in the brain and other neural
      tissues. Two of these lines also exhibit notable CAT expression in testis. The
      transgene is expressed at similar levels in many different regions of the central
      nervous system. Immunohistochemical staining detects the CAT marker protein in
      various cell populations of neuronal morphology within the brain and the spinal
      cord. Transgene expression is developmentally regulated in a way that correlates
      well with the expression of the endogenous synapsin I gene. Both follow a
      characteristic, biphasic postnatal time course with a maximum around day 20. We
      conclude that the DNA region investigated contains cis-regulatory elements
      sufficient to drive the expression of a reporter gene in a spatial and temporal
      pattern that resembles the expression of the endogenous synapsin I gene.

PMID- 8253779
TI  - Leukocyte common antigen-related receptor-linked tyrosine phosphatase. Regulation
      of mRNA expression.
AB  - Receptor-linked tyrosine phosphatases regulate cell growth by dephosphorylating
      proteins involved in tyrosine kinase signal transduction. Within this gene
      family, the leukocyte common antigen-related (LAR) gene is of particular interest
      with respect to the nervous system because it has sequence similarity to the
      neural cell adhesion molecule N-CAM and is located in a chromosomal region (1p32
      33) frequently deleted in neuroectodermal tumors. However, immunostaining has
      detected LAR in non-neural tissues, but not in the central nervous system,
      peripheral neurons, or adrenal medulla. In this study, rat brain cDNA library LAR
      clones corresponding to cytoplasmic and 3'-untranslated regions of human LAR were
      identified. Using probes derived from these clones, high stringency Northern
      blots revealed approximately 8 kilobase and variable length tissue- and cell
      specific LAR transcripts in cortex, brainstem, cerebellum, spinal cord,
      peripheral tissues, and cultured neural, glial, and pheochromocytoma cells. In
      situ hybridization showed expression by brain and dorsal root ganglion neurons.
      LAR expression was developmentally regulated in a region-dependent manner.
      Changes in LAR expression were also found during nerve growth factor-induced PC12
      pheochromocytoma cell differentiation and with contact-mediated inhibition of
      fibroblast growth. These observations and studies demonstrating neurotrophins
      functioning via tyrosine kinase receptors suggest that LAR represents an
      additional mechanism regulating neural development.

PMID- 8253780
TI  - Calcium/calmodulin-dependent protein kinase I. cDNA cloning and identification of
      autophosphorylation site.
AB  - Ca2+/calmodulin-dependent protein kinase I (CaM kinase I) was previously purified
      from bovine brain (Nairn, A. C., and Greengard, P. (1987) J. Biol. Chem. 262,
      7273-7281) based on its ability to phosphorylate the synaptic vesicle protein,
      synapsin I at site 1. The cDNA for this protein kinase has now been cloned from
      both a rat and a bovine brain cDNA library and the complete amino acid sequence
      of rat CaM kinase I determined. The rat cDNA encoded a protein of 331 amino acids
      with a calculated M(r) of 37,545, and the encoded kinase was expressed in
      bacteria as a glutathione S-transferase fusion protein. The resulting fusion
      protein was purified by Sepharose-CaM affinity chromatography and shown to be
      totally dependent on Ca2+ and CaM for activity. Furthermore, the purified kinase
      phosphorylates synapsin I at the same site (site 1) as the endogenous brain
      enzyme. CaM kinase I is homologous to other known protein kinases and contains
      all nine invariant amino acids conserved in the catalytic domain of this class of
      enzymes. CaM kinase I was most identical to CaM kinase II both in the catalytic
      domain and in a short region at the COOH-terminal that is predicted to be the
      calmodulin-binding domain. CaM kinase I appeared to be encoded by a single gene.
      RNase protection assays detected the mRNA encoding CaM kinase I in all tissues
      examined. High concentrations of the kinase mRNA were found in all regions of the
      brain with frontal cortex showing the greatest level. CaM kinase I was
      autophosphorylated in a Ca2+/CaM-dependent manner at a threonyl residue (Thr-177)
      which is located at a position equivalent to that of the threonyl residue (Thr
      197) autophosphorylated in cAMP-dependent protein kinase.

PMID- 8253781
TI  - The influence of 5'-secondary structures upon ribosome binding to mRNA during
      translation in yeast.
AB  - The influence of 5'-secondary structure formation and 5'-leader length upon mRNA
      translation in yeast has been analyzed using a closely related set of cat mRNAs
      (Vega Laso, M. R., Zhu, D., Sagliocco, F. A., Brown, A. J. P., Tuite, M. F., and
      McCarthy, J. E. G. (1993) J. Biol. Chem. 268, 6453-6462). A cat mRNA with a
      relatively short unstructured 5'-leader (22 bases) had a ribosome loading about
      half that of a cat mRNA with an unstructured 5'-leader of 77 bases. The
      introduction of 5'-secondary structures at various positions throughout the 5'
      leader of the cat mRNA inhibited translation initiation, the degree of inhibition
      being largely dependent upon the thermodynamic stability of the structure. Each
      mRNA carrying a 5'-secondary structure had a biphasic polysome distribution,
      indicating that the mRNA molecules were distributed between untranslated and well
      translated subpopulations. This suggests that once 5'-secondary structures are
      unwound, they reform slowly relative to the rate of translation initiation in
      yeast. Untranslated mRNA accumulated in 43 S preinitiation complexes, even when
      there were only 5 bases between the 5'-cap and the base of the hairpin. The data
      are consistent with the scanning hypothesis (Kozak, M. (1989) J. Cell. Biol. 108,
      229-241) and suggest that 40 S ribosomal subunits bind to mRNA early in the
      scanning process, probably before mRNA unwinding has taken place.

PMID- 8253782
TI  - Unique monocistronic operon (ptsH) in Mycoplasma capricolum encoding the
      phosphocarrier protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase
      system. Cloning, sequencing, and characterization of ptsH.
AB  - The region of the genome of Mycoplasma capricolum encompassing the gene (ptsH)
      encoding HPr, a general energy-coupling protein of the phosphoenolpyruvate:sugar
      phosphotransferase system, was cloned and sequenced. Examination of the sequence
      revealed a unique arrangement of the ptsH gene. In all other bacterial species
      characterized thus far, the ptsH gene is part of a polycistronic operon that
      includes the gene (ptsI) encoding Enzyme I of the phosphoenolpyruvate:sugar
      phosphotransferase system; the M. capricolum ptsH gene is part of a monocistronic
      operon that is situated between two open reading frames unrelated to
      phosphoenolpyruvate:sugar phosphotransferase system function. The gene
      immediately upstream of ptsH codes for a helicase, and the open reading frame
      immediately downstream of ptsH, although not homologous to any previously
      identified protein, contains a signature sequence characteristic of [C-5]
      cytosine-specific DNA methylases. The product of the ptsH gene has
      characteristics similar to the HPr protein produced by Gram-positive organisms:
      it has a greater sequence similarity to HPrs of Gram-positive bacteria than to
      those of Gram-negative organisms, it is phosphorylated by a protein kinase
      derived from Gram-positive organisms, and it complements sugar phosphorylation
      activity in Gram-positive extracts. The high calculated isoelectric point (pI =
      9.18) and the absence of glutamate residues in the C-terminal region distinguish
      the M. capricolum HPr from all previously described HPrs.

PMID- 8253783
TI  - Novel gangliosides containing the sialyl-Le(a) structure from a human rectal
      adenocarcinoma.
AB  - Oligosaccharides were released from the gangliosides of a human rectal
      adenocarcinoma with endoglycoceramidase (Rhodococcus sp. G-74-2) and then
      purified by affinity chromatography on a column of an immobilized monoclonal
      antibody, MSW 113. Structural studies, involving 600-MHz 1H NMR spectrometry,
      indicated the structures of these compounds to be as follows. [formula: see text]
      Three of these oligosaccharides, 2, 3, and 4, are novel as to ganglioside sugar
      chains and contain both lacto series types 1 and 2 chains. Oligosaccharides 3 and
      4 are unique in that they contain the sialyl-Le(a)-X structure in linear and
      branched structures. Gangliosides with the oligosaccharide structures presented
      above might be new potential tumor markers.

PMID- 8253784
TI  - Contiguous binding and inhibitory sites on kininogens required for the inhibition
      of platelet calpain.
AB  - Both high molecular weight kininogen (HK) and low molecular weight kininogens
      (LK) are potent tight binding inhibitors of platelet calpain (Ki = 2 nM), but the
      molecular basis for the inhibitory function is not well delineated. The amino
      acid sequences of the calpain inhibitory domain 2 from human and rat HK were
      compared for homology with the noninhibitory domains from human and rat domain 3
      and from domain 2 of rat T-kininogen, and two areas of nonconserved differences
      were detected. Computer three-dimensional models were constructed on a template
      built using the x-ray crystallographic data for cystatin, an evolutionary
      precursor of HK. Two nonconserved regions in the calpain inhibitory domains flank
      the highly conserved motif QVVAG to form a continuous surface for interaction
      with cysteine proteases. Three peptide sequences, components of the modeled
      surface, were chosen for synthesis from HK D-2: VHPISTQSPDLE (peptide 146-156,
      NH2-terminal), CTDNAYIDIQLRIASFSQNC (peptide 229-248, COOH-terminal), and
      CQRQVVAGLNFRIC (185-189, central) containing QVVAG. This last peptide differs
      from the natural sequence by substitutions of A185C and T195C. Peptides 185-198
      and 229-248 were folded by air oxidation of their cysteine residues and then
      tested for their ability to inhibit calpain and papain. The folded peptide 229
      248 inhibited calpain with an IC50 35 microM and unfolding reduced this effect.
      The folded peptide 185-198 did not inhibit calpain, but when preincubated with
      calpain, could block the inhibition by HK indicating a probable enzyme binding
      site. Peptide 146-157 did not inhibit calpain but could inhibit papain with an
      IC50 of 20 microM. We have thus defined separate binding and inhibitory sequences
      on HK which form a contiguous surface for thiol protease interactions.

PMID- 8253785
TI  - Genetic evidence for an interaction between the VirA sensor protein and the ChvE
      sugar-binding protein of Agrobacterium.
AB  - Most vir genes of Agrobacterium, which are required for tumorigenicity of the
      bacterium, are expressed in response to plant phenolics. The induction of vir is
      markedly enhanced by specific monosaccharides. Signals generated by both types of
      compound are transduced into Agrobacterium cells via the functions of the VirA
      membrane-bound sensor protein. A putative sugar-binding protein, known as ChvE,
      also functions at a step of the enhancement of vir induction by monosaccharides.
      To investigate the signal pathway of the enhancement by the sugars, we first
      isolated a virA mutant of Agrobacterium with a base substitution mutation that
      caused a single amino acid change in the periplasmic domain. The mutant exhibited
      no enhancement of vir induction by sugar and had severely attenuated
      tumorigenicity on Kalanchoe leaves. We then isolated two chvE mutants that
      restored sugar enhancement on the background of this virA mutation. One chvE
      mutant, which exhibited a higher level of sugar enhancement, restored the
      tumorigenicity of the virA mutant. Wild-type and suppressor ChvE proteins were
      localized in the periplasmic space. These results provide genetic evidence for
      the physical interaction between VirA and ChvE proteins in the periplasmic space
      of Agrobacterium, which enhances the cytoplasmic signal generated by phenolics.
      We also discuss the molecular architecture of the operon to which the chvE gene
      belongs.

PMID- 8253786
TI  - Use of transgenic mice to study regulation of gene expression in the parietal
      cell lineage of gastric units.
AB  - The mechanisms that regulate cell lineage-specific and differentiation-dependent
      patterns of gene expression in the gastric units of the stomach are largely
      unknown. Transgenic mice were generated in order to identify cis-acting sequences
      that determine the zymogenic cell-specific pattern of expression of the mouse
      intrinsic factor (InF) gene and the parietal cell-specific pattern of expression
      of the mouse H+/K(+)-ATPase beta-subunit gene. Portions of the 5'-nontranscribed
      domains of each gene were linked to the human growth hormone (hGH) gene beginning
      at its nucleotide +3. RNA blot hybridization studies combined with multilabel
      immunocytochemical surveys using a panel of lineage-specific antibodies and
      lectins indicated that nucleotides -1035 to +24 of the mouse H+/K(+)-ATPase beta
      subunit gene direct a pattern of reporter production which recapitulates the
      parietal cell-specific and developmental patterns of expression of the endogenous
      gene. Analysis of three mosaic founders containing H+/K(+)-ATPase beta-subunit
      1035 to +24/hGH+3 revealed that they had monophenotypic gastric units: a given
      unit contained either a wholly hGH-positive or a wholly hGH-negative population
      of parietal cells. These latter findings provide very strong evidence that
      gastric units are monoclonal, i.e. they are supplied by stem cells having one
      genotype. Although some, but not all, parietal cells are apparently derived from
      the same committed progenitor as zymogenic cells, virtually all parietal cells in
      a given gastric unit, but none of its zymogenic cells, express InF-1029 to
      +55/hGH+3. This suggests that InF-1029 to +55 may contain cis-acting sequences
      which allow parietal cell expression in other species (e.g. humans) but lack
      additional elements which normally function in mice to suppress InF expression in
      this lineage. The absence of hGH in zymogenic cells also means that the
      transcriptional regulatory environments of parietal and zymogenic cells derived
      from the same precursor are distinguishable by InF-1029 to +55. H+/K(+)-ATPase
      beta-subunit-1035 to +24 and InF-1029 to +55 are the only two sequences reported
      to date that are able to direct foreign gene expression exclusively to a gastric
      epithelial cell lineage in transgenic mice. This ability to deliver gene products
      to parietal cells can now be exploited to identify factors that control their
      normal proliferation and differentiation programs and/or to specifically alter
      their biological properties.

PMID- 8253787
TI  - A molecular mechanism for autoinhibition of myosin light chain kinases.
AB  - It is postulated that basic residues within the inhibitory region of myosin light
      chain kinase (MLCK) bind acidic residues within the catalytic core to maintain
      the kinase in an inactive form. In this study, we identified residues within the
      catalytic cores of the skeletal and smooth muscle MLCKs that may bind basic
      residues in inhibitory region. Acidic residues within the catalytic core of the
      rabbit skeletal and smooth muscle MLCKs were mutated and the kinetic properties
      of the mutant kinases determined. Mutation of 6 and 8 acidic residues in the
      skeletal and smooth muscle MLCKs, respectively, result in mutant MLCKs with
      decreases in KCaM (the concentration of calmodulin required for half-maximal
      activation of myosin light chain kinase) value ranging from 2- to 100-fold. Two
      inhibitory domain binding residues identified in each kinase also bind a basic
      residue in light chain substrate. The remaining mutants all have wild-type Km
      values for light chain. The predicted inhibitory domain binding residues are
      distributed in a linear fashion across the surface of the lower lobe of the
      proposed molecular model of the smooth muscle MLCK catalytic core. As 6 of the
      inhibitory domain binding residues in the smooth muscle MLCK are conserved in
      other Ca2+/calmodulin-dependent protein kinases, the structural basis for
      autoinhibition and activation may be similar.

PMID- 8253788
TI  - Perturbation of reaction-intermediate partitioning by a site-directed mutant of
      ribulose-bisphosphate carboxylase/oxygenase.
AB  - To explore the roles of active-site Glu48 of ribulose-bisphosphate
      carboxylase/oxygenase from Rhodospirillum rubrum, the E48Q mutant has been
      characterized with respect to kinetics and product distribution. Although the
      kcat for carboxylase activity is only 0.6% of the wild-type value, the mutant
      retains full activity in catalyzing the conversion of the carboxylated reaction
      intermediate to 3-phosphoglycerate and retains 10% of the normal activity in
      catalyzing the enolization of ribulose bisphosphate. Thus, the mutant is
      preferentially impaired in the carboxylation step. Partitioning of the
      enediol(ate) intermediate during turnover of ribulose bisphosphate is perturbed
      dramatically in the case of the mutant protein. Whereas the wild-type enzyme
      displays a CO2/O2 specificity factor of 11, the corresponding parameter of the
      mutant is only 0.3, thereby signifying a shift of the relative reactivity of the
      enediol(ate) in favor of O2. The mutant protein is also unable to protect the
      enediol(ate) against misprotonation with consequential conversion of ribulose
      bisphosphate to xylulose bisphosphate. This side reaction, undetected with wild
      type R. rubrum enzyme, proceeds as rapidly as carboxylation of D-ribulose 1,5
      bisphosphate by the E48Q mutant. Formation of xylulose bisphosphate by the mutant
      does not appear to account for the decline in carboxylase activity that occurs
      during the course of an assay. These studies demonstrate the multiple
      functionalities of Glu48 in the facilitation of catalysis and in directing
      intermediate partitioning in the preferred direction.

PMID- 8253789
TI  - Characterization of common salivary protein 1, a product of rat submandibular,
      sublingual, and parotid glands.
AB  - We have isolated and characterized cDNA clones derived from a developmentally
      regulated neonatal rat submandibular gland salivary protein gene called "common
      salivary protein 1" (CSP1). Identical clones were also identified in cDNA
      libraries from adult male parotid, submandibular, and sublingual glands. CSP1
      transcripts are at least 10-fold more abundant in the sublingual gland than in
      the submandibular or parotid glands. In situ hybridization and immunocytochemical
      localization demonstrated the presence of CSP1 transcripts and proteins in
      sublingual gland serous demilune cells, parotid and submandibular gland
      intercalated duct cells, and in the type III (proacinar) cells of the neonatal
      submandibular gland. This cell-type distribution is similar to that described by
      Ball and colleagues (Ball, W. D., Hand, A. R., and Johnson, A. O. (1988) Dev.
      Biol. 125, 265-279) for the developmentally regulated submandibular gland B1
      immunoreactive proteins. Immunoblotting of salivary secretion identified proteins
      of M(r) 20,000 in sublingual, 16,000 in submandibular and 22,000 and 16,000 in
      parotid gland. The M(r) 20,000 sublingual and 22,000 parotid proteins represent N
      glycosylated forms of a M(r) 16,000 apoprotein, suggesting that these salivary
      proteins arise by post-translational modification of a common precursor.

PMID- 8253790
TI  - Primary structure of pyruvate dehydrogenase kinase establishes a new family of
      eukaryotic protein kinases.
AB  - We recently reported molecular cloning of the branched chain alpha-ketoacid
      dehydrogenase kinase, the first mitochondrial protein kinase to be cloned (Popov,
      K. M., Zhao, Y., Shimomura, Y., Kuntz, M. J., and Harris, R. A. (1992) J. Biol.
      Chem. 267, 13127-13130). From a search for proteins related to the branched chain
      alpha-ketoacid dehydrogenase kinase, a cDNA encoding the 434 amino acid residues
      corresponding to pyruvate dehydrogenase kinase has been cloned from a rat heart
      cDNA library. Evidence that the clone codes for pyruvate dehydrogenase kinase
      includes: (a) the deduced amino acid sequence is identical to the partial
      sequence of the kinase determined by direct sequencing; (b) expression of the
      cDNA in Escherichia coli resulted in synthesis of a protein that phosphorylated
      and inactivated the pyruvate dehydrogenase complex; (c) kinase activity of the
      recombinant protein is sensitive to inhibition by a specific inhibitor of
      pyruvate dehydrogenase kinase; and (d) antiserum raised against the recombinant
      protein recognized the protein subunit known to correspond to pyruvate
      dehydrogenase kinase in a highly purified preparation of the pyruvate
      dehydrogenase complex. Like the branched chain alpha-ketoacid dehydrogenase
      kinase, pyruvate dehydrogenase kinase lacks motifs usually associated with
      eukaryotic Ser/Thr-protein kinases. Considerable sequence similarity exists
      between these mitochondrial protein kinases and members of the prokaryotic
      histidine kinase family, a diverse set of sensing and response systems important
      in the regulation of bacterial processes. Thus, molecular cloning of these
      proteins establishes a new eukaryotic family of protein kinases that is related
      to a prokaryotic family of protein kinases.

PMID- 8253791
TI  - Role of transmembrane domains in assembly and intracellular transport of the CD8
      molecule.
AB  - Previous studies have shown that CD8 can be present at the cell surface either as
      a disulfide-linked homodimer of CD8 alpha or as a disulfide-linked heterodimer of
      CD8 alpha and CD8 beta. Here we analyzed the assembly and intracellular transport
      of CD8 with particular emphasis on the role of the transmembrane domains. A
      chimeric protein (alpha T alpha) made by replacing the transmembrane domain of
      CD8 alpha with that of the interleukin-2 receptor alpha chain (Tac) exhibited
      reduced ability to form homodimers, while a mutant of Tac containing the CD8
      alpha transmembrane domain (T alpha alpha) dimerized efficiently. Contrary to CD8
      alpha, CD8 beta expressed alone was retained in the endoplasmic reticulum (ER).
      Only a small amount of CD8 beta formed homodimers, and these also remained in the
      ER. A mutant of CD8 beta that dimerized efficiently was also retained in the ER,
      thus proving that ER retention of CD8 beta is not due to its poor
      homodimerization. Rather, the extracellular domain of CD8 beta requires
      interaction with that of CD8 alpha to exit the ER. The transmembrane domain of
      CD8 beta was also shown to participate in ER retention by preventing exit of
      monomeric CD8 beta out of the ER. These findings demonstrate the role of
      transmembrane domains in assembly and intracellular transport of the CD8
      molecule.

PMID- 8253792
TI  - Aldosterone-induced and GTP-stimulated methylation of a 90-kDa polypeptide in the
      apical membrane of A6 epithelia.
AB  - Aldosterone treatment of A6 cultured renal epithelial cells methylates the apical
      membrane, and we examined the aldosterone-induced carboxymethylation of the
      apical membrane of these cells to determine the targeted polypeptides. Methionine
      deprived A6 cells were incubated with aldosterone and [3H]methionine. Homogenates
      and apical membranes were solubilized and analyzed by SDS-polyacrylamide gel
      electrophoresis. Label incorporation in a 90-kDa polypeptide was more intense (4
      fold) in membranes after aldosterone compared to control. For in vitro
      methylation, membranes were isolated, incubated with S-adenosyl-L-[methyl
      3H]methionine, and analyzed for 3H-methyl uptake. Label incorporation was low in
      control membranes but markedly stimulated (4-fold) in membrane preparations from
      aldosterone-treated cells. Guanosine 5'-O-(3-thiotriphosphate) increased in vitro
      methylation of a 90-kDa polypeptide 5-fold in control membranes but after
      aldosterone, where methylation was already stimulated, little change was
      observed. We conclude that aldosterone induces methylation of an apical membrane
      90-kDa polypeptide, possibly a subunit of the epithelial Na+ channel, in a GTP
      dependent manner, and this may be one of the final steps in a cascade of
      reactions leading to the natriferic action of this hormone.

PMID- 8253793
TI  - Transactivation properties of retinoic acid and retinoid X receptors in mammalian
      cells and yeast. Correlation with hormone binding and effects of metabolism.
AB  - The binding affinities of 9-cis-retinoic acid (9-cis-RA) and all-trans-retinoic
      acid (t-RA) for retinoic acid receptors (RAR) alpha, beta, and gamma and for
      retinoid X receptors (RXR) alpha, beta, and gamma were determined using the
      recombinant receptor proteins and were compared with each hormone's ability to
      activate transcription through the receptors in mammalian and yeast cell systems.
      9-cis-RA bound to both the RXRs (Kd values = 1.4-2.4 nM) and the RARs (Kd values
      = 0.2-0.8 nM). The ability of 9-cis-RA to bind to the RARs and RXRs correlated
      with its ability to produce similar transactivation profiles with these receptors
      in mammalian and yeast cell assays. t-RA bound to the RARs (Kd values = 0.2-0.4
      nM) and activated transcription through the RARs in mammalian and yeast cells. In
      contrast, while t-RA did not bind to the RXRs, it did activate the RXRs, albeit
      less potently than 9-cis-RA, in mammalian cells. In yeast, however, the RXRs
      activated transcription only in the presence of 9-cis-RA, not with t-RA. While
      RAR gamma is activated in yeast by either t-RA or 9-cis-RA, the overall level of
      transcription was increased upon the addition of hormone-occupied RXR. Metabolism
      studies suggest that while there was no cell-dependent interconversion between t
      RA and 9-cis-RA in yeast, there was cell-dependent conversion of 9-cis-RA to t-RA
      in mammalian cells [corrected].

PMID- 8253794
TI  - Biosynthetic mechanisms for the addition of polylactosamine to chondrocyte
      fibromodulin.
AB  - The cartilage matrix glycoprotein fibromodulin contains four N-linked
      glycosylation sites which act as acceptors for the addition of sulfated
      polylactosamine (keratan sulfate). In the present study we examined the
      biosynthetic processing of these N-linked oligosaccharides for subsequent
      addition of polylactosamine. Chondrocytes were treated with castanospermine, 1
      (+)deoxymannojirimycin, and swainsonine, radiolabeled with [3,4,5-3H]leucine, [2
      3H]mannose, or [6-3H]glucosamine, and newly synthesized fibromodulin was
      immunoprecipitated for analysis. Castanospermine and 1-(+)deoxymannojirimycin
      inhibited polylactosamine addition, whereas swainsonine was not effective. This
      indicated that the linkage regions must be processed to GlcNAc(Man)5(GlcNAc)2Asn
      but do not require further modification to GlcNAc(Man)3(GlcNAc)2Asn. In both
      control and swainsonine-treated cells one or two N-linked oligosaccharides per
      molecule were modified with polylactosamine containing 4-6 repeating disaccharide
      units. Moreover, a single short chain was added either to the C-3 or the C-6
      branch in control cultures, whereas only the C-3 branch was substituted in the
      presence of swainsonine. Analysis of endo-beta-galactosidase and keratanase II
      digestion products of the polylactosamine chains synthesized in both culture
      conditions showed that only about 25% of the hexosamine residues and less than 5%
      of the adjacent galactose residues were substituted with sulfate. These findings
      are discussed in relation to the regulation of fibromodulin glycosylation and the
      likely influence of polylactosamine structure on the extracellular interactions
      and turnover of fibromodulin.

PMID- 8253795
TI  - Rhodopsin mutations responsible for autosomal dominant retinitis pigmentosa.
      Clustering of functional classes along the polypeptide chain.
AB  - Over 40 mutations in the rhodopsin gene have been identified in patients with
      autosomal dominant retinitis pigmentosa. Twenty-one of these mutations have been
      introduced into a human rhodopsin cDNA by site-directed mutagenesis, and the
      encoded proteins have been produced by transfection of a human embryonic kidney
      cell line (293S). Three of the mutant proteins (G51V, V345M, and P347S) resemble
      the wild type in yield, regenerability with 11-cis-retinal, and accumulation in
      the plasma membrane (class I). The remaining 18 mutant proteins are produced at
      lower levels, regenerate variably or not at all with 11-cis-retinal, and
      accumulate partially or predominantly in the endoplasmic reticulum (class II).
      Together with an earlier analysis of 13 mutant rhodopsins (Sung, C.-H.,
      Schneider, B., Agarwal, N., Papermaster, D.S., and Nathans, J. (1991) Proc. Natl.
      Acad. Sci. U.S.A. 88, 8840-8844), these experiments define distinct classes of
      biochemical defects in human rhodopsin and further show that amino acid
      substitutions in class II reside within the transmembrane and extracellular
      domains, whereas class I mutants cluster in the first transmembrane domain and at
      the extreme carboxyl terminus.

PMID- 8253796
TI  - Purification and characterization of the receptor for pituitary adenylate cyclase
      activating polypeptide.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid
      peptide (PACAP38) or a truncated peptide with the same 27 amino-terminal residues
      (PACAP27). The PACAP receptor was solubilized from bovine brain membranes with
      digitonin and purified 30-fold by the combination of DEAE-Toyopearl and
      hydroxylapatite chromatographic analyses. The partially purified PACAP receptors
      were mixed with biotinylated PACAP27 to form receptor-ligand complexes and then
      adsorbed onto avidin-agarose. The adsorbed PACAP receptors were eluted with an
      acidic buffer containing 1.0 M NaCl (pH 4.0). The eluted receptors were purified
      further by hydroxylapatite and gel filtration chromatography. A single protein
      band with a M(r) = 55,000-60,000 was found in the final preparation by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining. Affinity
      labeling of the purified receptors with 125I-PACAP27 labeled the M(r) 55,000
      60,000 protein specifically. The dissociation constant and the specific activity
      of the purified receptors were 25.8 pM and 17.2 nmol of ligand binding per mg of
      protein, respectively. Inhibitory constants determined by competitive binding
      experiments were 30.0 pM for PACAP27, 4.6 pM for PACAP38, and 37.3 nM for
      vasoactive intestinal peptide. Therefore, the purified PACAP receptor retained
      high affinity and ligand specificity. The sequence of the amino-terminal 29
      residues was derived from the purified receptor.

PMID- 8253797
TI  - Transcriptional enhancer factor-1 in cardiac myocytes interacts with an alpha 1
      adrenergic- and beta-protein kinase C-inducible element in the rat beta-myosin
      heavy chain promoter.
AB  - In cultured rat cardiac myocytes, a 20-base pair sequence (-215/-196) of the rat
      beta-myosin heavy chain (MHC) promoter mediates induction by both alpha 1
      adrenergic stimulation and a constitutively activated beta-protein kinase C
      (PKC), and binds cardiac myocyte nuclear factor(s) through an "enhancer core"
      element (5'-TGTGG-TATG-3') (Kariya, K., Karns, L. R., and Simpson, P. C. (1994)
      J. Biol. Chem. 269, in press). Here, we report identification of this enhancer
      core binding factor as the rat homologue of transcriptional enhancer factor-1
      (TEF-1), a human transcription factor for viral enhancers. In gel mobility shift
      and immunoblot analyses, the myocyte factor and human TEF-1 were
      indistinguishable in terms of sequence recognition, mobility, and
      immunoreactivity. Furthermore, DNA binding activity for the beta-MHC enhancer
      core and TEF-1 immunoreactivity correlated closely. These results are the first
      to suggest a role for TEF-1 in transcriptional regulation by PKC. The data also
      provide direct evidence for interaction of TEF-1 with the beta-MHC promoter,
      supporting a function for TEF-1 in regulation of cellular gene expression, as
      well as viral, and outline a pathway for alpha 1-adrenergic regulation of beta
      MHC gene transcription in cardiac myocytes.

PMID- 8253798
TI  - Efficient transcription of a DNA template associated with histone (H3.H4)2
      tetramers.
AB  - A histone-DNA transcription template has been assembled, by dialysis against
      decreasing salt concentrations, from pGEMEX-1 (4 kilobases), a plasmid containing
      a promoter for bacteriophage T7 RNA polymerase, and from isolated histone
      (H3.H4)2 tetramers. Electron microscopy after psoralen cross-linking shows that
      each histone tetramer protects approximately 80 base pairs of DNA from psoralen
      action and that, under the employed conditions, an average of 15 tetramer
      particles are assembled per DNA molecule. This (H3.H4)2-DNA template is
      efficiently transcribed in vitro by T7 RNA polymerase as compared to naked DNA.
      The presence of (H3.H4)2 tetramers does not affect initiation, in contrast with
      the complete histone octamer, (H2A.H2B.H3.H4)2, assembled with the complementary
      addition of H2A.H2B dimers, which causes transcriptional inhibition mainly by
      blocking initiation.

PMID- 8253799
TI  - Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig
      cells.
AB  - We have isolated complementary DNA clones coding for a novel member of the
      insulin-like hormone super-family from a boar testis cDNA library. Northern blot
      analysis and in situ hybridization revealed that the gene is expressed
      exclusively in prenatal and postnatal Leydig cells. We have tentatively proposed
      the name Leydig insulin-like (Ley I-L) for the gene and its encoded protein. The
      Leydig insulin-like protein is synthesized as a 131-amino acid preproprotein,
      which contains a 24-amino acid signal peptide. Comparison of the deduced amino
      acid sequence of pro-Leydig insulin-like protein with members of the insulin-like
      hormone superfamily predicts that the biologically active protein, after
      proteolytic processing of the C-peptide, consists of a 32-residue-long B-chain
      and a 26-residue-long A-chain and has a molecular size of 6.25 kDa.

PMID- 8253800
TI  - Calcium affinity of the NH2-terminal epidermal growth factor-like module of
      factor X. Effect of the gamma-carboxyglutamic acid-containing module.
AB  - The NH2-terminal epidermal growth factor (EGF)-like module of vitamin K-dependent
      coagulation factors IX and X and protein C each has one calcium binding site.
      This module (residues 45-86) from factor X has been isolated previously and found
      to bind calcium with a Kd of 2.2 mM at physiological pH and ionic strength. We
      have now demonstrated that it binds calcium with a Kd of 120 microM in a fragment
      that consists of the Gla module and the NH2-terminal EGF-like module. The
      presence of the Gla module (residues 1-44) increases the calcium affinity of the
      site in the EGF-like module approximately 20-fold, thus making it essentially
      saturated in vivo. Decarboxylation of the Gla residues to Glu has no significant
      effect on the calcium affinity of the EGF-like module. A proteolytic fragment of
      factor X (residues 29-86) and a synthetic peptide (residues 34-86), folded to a
      native conformation, were used to demonstrate that the contribution of the Gla
      module to the calcium affinity of the site in the EGF-like module is mediated by
      its 17 COOH-terminal residues, 12 of which form an alpha-helix in the intact Gla
      module. In the NMR structure of the NH2-terminal EGF-like module in factor X,
      five calcium ligating groups have been identified (Selander-Sunnerhagen, M.,
      Ullner, M., Persson, E., Teleman, O., Stenflo, J., and Drakenberg, T. (1992) J.
      Biol. Chem. 267, 19642-19649). As calcium usually requires seven to eight oxygen
      ligands, there is reason to believe that the Gla module contributes ligands, or
      negative charge, to increase the calcium affinity. Our findings suggest that the
      calcium affinity of EGF-like modules in other proteins may also be influenced by
      neighboring modules.

PMID- 8253801
TI  - Characterization of placentation-specific binucleate cell glycoproteins
      possessing a novel carbohydrate. Evidence for a new family of pregnancy
      associated molecules.
AB  - The ovine binucleate cell-specific glycoproteins recognized by the monoclonal
      antibody SBU-3 first appear at the initiation of placentation, and their
      expression continues throughout gestation. These placenta-specific proteins have
      not been detected in any other adult or fetal sheep tissues and are specific to
      the materno-fetal interface. The SBU-3 monoclonal antibody recognizes the
      carbohydrate epitope common to a group of proteins ranging in molecular mass from
      30 to 200 kDa whose function during pregnancy remains undefined. The biochemical
      properties of these uniquely expressed glycoproteins were investigated by
      analyzing both the carbohydrate and protein portion of the molecules. Analysis of
      phytohemagglutinin and concanavalin A binding to electrophoretically separated
      SBU-3 proteins revealed that the major proteins between 40 and 70 kDa bind
      phytohemagglutinin. In contrast, concanavalin A bound only to minor proteins in
      the SBU-3 glycoprotein preparation. Analysis of the carbohydrate conjugated to
      the SBU-3 glycoproteins revealed that the major chains are sialylated O-linked
      and complex partially sialylated multiple antennary N-linked chains. The presence
      of N-glycolylneuraminic acid in an N-linked structure indicates the unique nature
      of this carbohydrate epitope. The differential binding to phytohemagglutinin and
      concanavalin A provided a method for further purification and characterization of
      the major protein components with monoclonal antibody immunoaffinity-purified SBU
      3 proteins being further separated by concanavalin A-Sepharose chromatography.
      Microsequence analysis of the major non-concanavalin A-binding proteins (69, 62,
      and 57 kDa) revealed partial homology to ovine and bovine pregnancy-associated
      glycoprotein and rabbit pepsinogen F. Immunoblot analysis of the SBU-3 proteins
      showed cross-reactivity with polyclonal antisera directed against ovine placental
      associated glycoprotein and pregnancy-specific glycoprotein B. These results
      suggest that together these glycoproteins represent members of a binucleate cell
      derived family of pregnancy-associated molecules in the ruminant placenta.

PMID- 8253802
TI  - Identification of cyclic ADP-ribose-binding proteins by photoaffinity labeling.
AB  - We have synthesized 8-azido-cyclic ADP-ribose (8N3-cADPR) and [32P]8-azido-cyclic
      ADP-ribose ([32P]8N3-cADPR) in order to characterize cyclic ADP-ribose-(cADPR)
      binding sites in sea urchin egg homogenates. 8N3-cADPR was an antagonist of cADPR
      since it did not induce Ca2+ release from egg microsomes but did inhibit the
      ability of cADPR to do so. The effect of 8N3-cADPR was reversible and could be
      overcome by high concentrations of cADPR, suggesting that both were acting on the
      same site. This was supported by the fact that 8N3-cADPR effectively competed for
      [32P]cADPR binding to microsomes. Reciprocally, binding of [32P]8N3-cADPR could
      also be selectively displaced by cADPR and 8N3-cADPR, but not by ADP-ribose.
      These results indicate that 8N3-cADPR binds specifically to the cADPR-binding
      sites and inhibits cADPR from releasing Ca2+. Photolysis of microsomes
      preincubated with [32P]8N3-cADPR resulted in specific labeling of proteins of 140
      and 100 kDa, which could be prevented by 8N3-cADPR or nanomolar concentrations of
      cADPR, but not by micromolar concentrations of ADP-ribose, AMP, ADP, ATP, cyclic
      AMP or inositol 1,4,5-trisphosphate. Caffeine, an agonist of Ca(2+)-induced Ca2+
      release, preferentially inhibited the labeling of the 100 kDa as compared to the
      140-kDa protein. These results suggest that cADPR may not interact directly with
      the ryanodine receptor, but may instead, exert its effect through intermediate
      proteins.

PMID- 8253803
TI  - Recombinant human milk bile salt-stimulated lipase. Catalytic activity is
      retained in the absence of glycosylation and the unique proline-rich repeats.
AB  - Human milk bile salt-stimulated lipase ensures efficient utilization of
      triacylglycerol by breast-fed infants. Cloning and sequencing of cDNA have
      revealed that the peptide chain consists of 722 amino acid residues showing only
      little homology to typical lipases. The sequence is identical to that of
      pancreatic carboxylic-ester hydrolase. The COOH-terminal part contains 16 proline
      rich repeats of 11 residues with O-linked carbohydrate. The only N-linked sugar
      chain is situated close to the active-site serine. Using C127 cells and a bovine
      papilloma virus vector, high and stable expression of full-length lipase and of
      several variants, obtained by site-directed mutagenesis, was achieved. The
      produced proteins were purified and further characterized. Variants lacking all,
      or all but two, repeats were active with similar specific activity and the same
      bile salt dependence as the native milk enzyme. Changing the asparagine necessary
      for N-glycosylation gave the same principal results. Active recombinant full
      length lipase was also produced in a bacterial system. We conclude that neither
      glycosylation (N- or O-linked) nor the proline-rich repeats are essential for
      catalytic activity or bile salt activation of human milk bile salt-stimulated
      lipase.

PMID- 8253804
TI  - Absence of electron transport (Rho 0 state) restores growth of a manganese
      superoxide dismutase-deficient Saccharomyces cerevisiae in hyperoxia. Evidence
      for electron transport as a major source of superoxide generation in vivo.
AB  - To address the possibility that electron transport is a biologically significant
      source of superoxide anion (O2-.) during exposure to hyperoxia in vivo, we
      constructed Saccharomyces cerevisiae strains with selective disruptions in the
      gene encoding the mitochondrial manganese-containing superoxide dismutase (Mn
      SOD) and/or genes encoding proteins critical for complexes in electron transport.
      We hypothesized that complete absence of electron transport would restore growth
      in hyperoxia to a Mn-SOD-deficient yeast. We found that yeast deficient in Mn-SOD
      activity failed to grow normally in hyperoxia (95% O2, 5% CO2). In contrast, Mn
      SOD-deficient yeast with complete absence of electron transport (the Rho 0 state)
      grew normally in hyperoxia. By comparison, Mn-SOD-deficient yeast which were
      deficient only in cytochrome-c-oxidase, the terminal step in electron transport,
      had only partially restored growth in hyperoxia. Our results indicate that
      electron transport is a major source of O2-. in vivo, and that the principal site
      of this O2-. production is proximal to the cytochrome-c-oxidase complex.

PMID- 8253805
TI  - Primary structure of the soluble lactose binding lectin L-29 from rat and dog and
      interaction of its non-collagenous proline-, glycine-, tyrosine-rich sequence
      with bacterial and tissue collagenase.
AB  - A lactose-binding lectin from rat lung (RL-29) and a related lectin from Madin
      Darby canine kidney (MDCK) cells have been analyzed with the primary goal of
      identifying post-translational modifications. The sequences show that RL-29 and
      the dog lectin are homologues of a lectin designated here as L-29 and elsewhere
      as CBP-35, epsilon BP, Mac-2, or L-34. RL-29 has a 140-amino-acid COOH-terminal
      carbohydrate-binding domain, a 20-amino-acid NH2-terminal domain, and an
      intervening domain consisting of 11 repeating elements rich in Pro, Gly, and Tyr
      (R-domain). The dog homologue has 14 repeating elements in its R-domain
      explaining its larger size. The sensitivity of the R-domain to bacterial
      collagenase allowed us to isolate the NH2-terminal domain and show that the NH2
      terminus was blocked by acetylation and, in the accompanying paper (Huflejt, M.
      E., Turck, C. W., Lindstedt, R., Barondes, S. H., and Leffler, H. (1993) J. Biol.
      Chem. 268, 26712-26718), that the NH2-terminal domain is phosphorylated. In
      addition, we unexpectedly found an endogenous component, resembling 92-kDa type
      IV collagenase, that co-purified with L-29 and slowly digested the R-domain.
      Hence, L-29 is a substrate for bacterial and tissue collagenases even though the
      R-domain is non-collagenous. Moreover, the co-purification suggests a non
      enzymatic interaction between 92-kDa collagenase and L-29.

PMID- 8253806
TI  - L-29, a soluble lactose-binding lectin, is phosphorylated on serine 6 and serine
      12 in vivo and by casein kinase I.
AB  - L-29, a mammalian soluble lactose-binding lectin, was previously shown to be
      phosphorylated in confluent 3T3 fibroblasts (Cowles, E. A., Agrwal, N., Anderson,
      R. L., and Wang, J. L. (1990) J. Biol. Chem. 265, 17706-17712), which contain a
      small amount of this protein. We have determined the site of phosphorylation on L
      29, taking advantage of the abundance of L-29 (about 1% of total soluble cell
      protein) in confluent polarized Madin-Darby canine kidney (MDCK) cells.
      Approximately 15-20% of the L-29 is phosphorylated in these cells. Phosphoamino
      acid analysis showed phosphate incorporation only at serine. Analysis of
      chymotryptic and endoproteinase Asp-N-generated NH2-terminal fragments by Edman
      degradation showed that 90% of the phosphate was at Ser6 and 10% at Ser12. The
      sequence surrounding Ser6, which is conserved in all known L-29 sequences,
      indicated that this serine might be phosphorylated by casein kinase I or casein
      kinase II. Reaction of human recombinant L-29 with [gamma-32P]ATP and each of
      these casein kinases showed that only casein kinase I catalyzed significant
      incorporation of 32P into L-29; and, as with the L-29 from the MDCK cell
      extracts, most of the phosphate was incorporated at Ser6 and a small amount was
      incorporated at Ser12.

PMID- 8253807
TI  - The human immunodeficiency virus type 1 long terminal repeat is activated by
      monofunctional and bifunctional DNA alkylating agents in human lymphocytes.
AB  - The activation of the human immunodeficiency virus, type 1 (HIV-1) by the DNA
      alkylating agents ethyl methanesulfonate, methyl methanesulfonate, and mitomycin
      C was observed in human B lymphocytes transiently transfected with plasmids in
      which the HIV-1 long terminal repeat (LTR) directed the expression of the
      bacterial chloramphenicol acetyltransferase gene. Deletion of the two NF-kappa B
      binding sites of LTR abolished the HIV-1 activation induced by the three
      mutagens, while deletion of the three Sp1-binding sites slightly reduced it.
      Electrophoretic mobility shift assays revealed an increased binding to the kappa
      B sites of HIV-1 LTR in the nuclear extracts of human B lymphocytes upon mutagen
      treatment, while binding to Sp1 sites was unaffected. The TAR region was also
      involved in the mutagen-mediated activation of HIV-1 LTR inasmuch as a small
      deletion in the TAR sequence (nucleotides +34 to +37) greatly decreased the
      induction of HIV-1 expression. Moreover, an enhanced binding activity to the TAR
      DNA sequence (nucleotides +24 to +47) was observed in nuclear extracts of mutagen
      treated lymphocytes. Thus, both the enhancer and the 5'-untranslated region of
      HIV-1 functionally cooperate in the mutagen-mediated induction of HIV-1
      expression.

PMID- 8253808
TI  - Activity of calf thymus DNA helicase E on cis-diamminedichloroplatinum (II)
      damaged DNA.
AB  - Calf DNA helicase E (hel E) is a moderately processive, 3' to 5' helicase, active
      on nicked DNA, that we have proposed to have a role in DNA repair (Turchi, J. J.,
      Murante, R. S., and Bambara, R. A. (1992) Nucleic Acids Res. 20, 6075-6080). Here
      we have examined its activity on a series of cis-diamminedichloroplatinum (II)
      (cis-DDP)-modified DNA substrates. Hel E was capable of efficiently displacing a
      primer strand containing, in an internal position, a cis-DDP-modified dGG. In a
      two-primer model system, calf DNA polymerase epsilon could successfully extend an
      upstream primer through a cis-DDP-modified down-stream primer, to the end of the
      complementary template strand, in a reaction dependent on hel E. However, the
      translocation of hel E was blocked by cis-DDP modification of the template
      strand. Primer displacement was completely prevented if the modified site was
      located just upstream of the primer. The DNA-dependent ATPase activity of
      helicase E was also reduced by cis-DDP modification of the template DNA.
      Substrate competition experiments indicated that cis-DDP-modified DNA templates
      did not sequester hel E. Substrate titration experiments suggested that there is
      a short delay without ATP hydrolysis before dissociation of helicase E from cis
      DDP-modified template sites. Interestingly, hel E could displace a primer if the
      cis-DDP modification was on the template within the annealed region. Possible
      explanations for this are discussed. Taken together, these results are consistent
      with the proposal that hel E participates in DNA repair by displacing segments of
      damaged DNA.

PMID- 8253809
TI  - Function of the zinc finger in Escherichia coli Fpg protein.
AB  - Fpg protein of Escherichia coli cleaves duplex DNA containing the oxidatively
      damaged base 8-oxo-7,8-dihydroguanine (Tchou, J., Kasai, H., Shibutani, S.,
      Chung, M.-H., Laval, J., Grollman, A. P., and Nishimura, S. (1991) Proc. Natl.
      Acad. Sci. U.S.A. 88, 4690-4694). This DNA repair enzyme contains one zinc
      atom/protein molecule (Boiteux, S., O'Connor, T. R., Lederer, F., Gougette, A.,
      and Laval, J. (1990) J. Biol. Chem. 265, 3916-3922); its N-glycosylase and
      apurinic/apyrimidinic lyase activities are physically associated. Amino acid
      sequence analysis reveals a putative single zinc finger motif of the CC/CC type
      located near the carboxyl terminus. A gel mobility shift assay was used to assay
      binding of Fpg protein to a noncleavable substrate analog, namely an
      oligodeoxynucleotide duplex containing a single tetrahydrofuran residue. High
      resolution hydroxyl radical DNA footprinting showed protection centered around
      the tetrahydrofuran residue. No footprint was observed on the complementary
      strand. To establish the role of COOH-terminal zinc finger in DNA binding and/or
      DNA cleavage, amino acid substitutions and an amber mutation were introduced at
      Cys-244 (C244S, C244H, C244A, and C244amber). In addition, a double amino acid
      substitution was generated at Cys-244 and Cys-247 (C244S/C247S). These mutant Fpg
      proteins lack DNA binding or cleavage activity, as tested in crude lysates of
      Escherichia coli. Wild type Fpg protein contains one zinc/protein molecule,
      whereas the mutant Fpg protein (C244S/C247S) lacks zinc, as measured by atomic
      absorption spectroscopy. This mutation did not significantly alter secondary
      structure, as assessed by circular dichroism spectroscopy. Our results suggest
      that Fpg protein utilizes its single COOH-terminal zinc finger motif in DNA
      binding.

PMID- 8253810
TI  - Site-specific photocross-linking reveals that Sec61p and TRAM contact different
      regions of a membrane-inserted signal sequence.
AB  - A chemically charged amber suppressor tRNA was used to introduce the
      photoactivatable amino acid (Tmd)Phe at a selected position within the signal
      sequence of the secretory protein preprolactin. This allowed the interactions of
      the NH2-terminal, the central, and the COOH-terminal regions of the signal
      sequence to be investigated during insertion into the membrane of the endoplasmic
      reticulum (ER). We found that different regions of the nascent chains were
      photocross-linked to different ER proteins. The TRAM protein (translocating chain
      associating membrane protein) contacts the NH2-terminal region of the signal
      sequence while the mammalian Sec61p contacts the hydrophobic core of the signal
      sequence and regions COOH-terminal of this. These results suggest that the ER
      translocation complex is composed of heterologous protein subunits which contact
      distinct regions of nascent polypeptides during their membrane insertion.

PMID- 8253811
TI  - Effect of acylation on structure and function of surfactant protein C at the air
      liquid interface.
AB  - Pulmonary surfactant protein C (SP-C) is a small hydrophobic peptide that is
      palmitoylated on 2 adjacent cysteine residues. SP-C enhances the adsorption of
      phospholipids into a monolayer. The function of the acylation is not clear yet.
      The experiments described in this article were carried out in order to
      investigate the function of SP-C acylation in (protein-catalyzed) lipid monolayer
      formation, and in bilayer interactions. Palmitoylated and nonpalmitoylated human
      recombinant SP-C were used. In addition, a nonacylated SP-C with a Cys-->Ser
      mutations was included in these studies. In Wilhelmy plate experiments using
      negatively charged, protein-containing phospholipid monolayers and negatively
      charged vesicles, CaCl2 was required to obtain a maximal insertion rate of lipids
      into the monolayer. If the negatively charged phospholipids in the monolayer were
      replaced by neutral phospholipids, CaCl2 was only required to show a maximal SP-C
      catalyzed insertion rate (if the molecule is palmitoylated, but not if
      nonpalmitoylated proteins were added). In pressure area measurements, the
      palmitoylated protein showed a different change in pressure as a function of the
      surface area, as compared with the nonpalmitoylated proteins. Circular dichroism
      experiments showed that all three proteins had a high content of alpha-helix. All
      three proteins showed a preferential orientation at the air-water interface, but
      the palmitoylated protein has an orientation which is more parallel to the
      monolayer than that of the nonpalmitoylated proteins. It is concluded that
      acylation of SP-C alters structural and physical properties of this protein.

PMID- 8253812
TI  - Purification and characterization of a phosphoramidon-sensitive endothelin
      converting enzyme in porcine aortic endothelium. OFF.
AB  - An enzyme that catalyzes the conversion of big endothelin-1 to endothelin-1,
      designated as endothelin-converting enzyme, was solubilized with Lubrol PX from
      the membrane fraction of porcine aortic endothelium and was purified by
      sequential chromatography on DEAE-agarose, Ricinus communis agglutinin 120
      agarose, peanut agglutinin-agarose, Mono Q, and TSK G3000SWXL columns.
      Approximately 12,000-fold purification of the membrane fraction enzyme was
      achieved. The purified enzyme had a very narrow neutral pH optimum and was
      inhibited by EDTA, 1,10-phenanthroline, phosphoramidon, and low concentrations of
      some divalent cations (Cu2+,Zn2+,Co2+,Fe2+) but not by thiorphan. Addition of
      Zn2+ was most effective for the restoration of the EDTA-inactivated enzyme. The
      purified enzyme showed the highest affinity for big endothelin-1 among big
      endothelin isopeptides, and the Km for big endothelin-1 and the corresponding
      Vmax for endothelin-1 formation were 3.3 +/- 0.3 microM and 0.41 +/- 0.02
      mumol/min/mg of protein, respectively. The carboxyl-terminal sequence from His27
      to Gly34 and Trp21 was essential for recognition by this enzyme, while the
      presence of the amino-terminal loop structure reduced the hydrolysis rate. The
      purified enzyme showed an isoelectric point of 4.1. The molecular mass was
      estimated to be 131 kDa by sucrose density gradient centrifugation, and a value
      of 120 kDa was obtained by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, indicating that endothelin-converting enzyme is a monomeric
      glycoprotein.

PMID- 8253813
TI  - Cloning and expression of a cDNA for the human prostaglandin E receptor EP1
      subtype.
AB  - A functional cDNA clone coding for the human prostaglandin E receptor EP1 subtype
      has been isolated from a human erythroleukemia cell cDNA library probed by low
      stringency hybridization using a polymerase chain reaction fragment of the human
      thromboxane receptor. The human EP1 receptor is comprised of 402 amino acids with
      a predicted molecular mass of 41,858 and has the topography common to all G
      protein-coupled receptors with seven predicted transmembrane spanning domains.
      Prostaglandin (PG) E2 challenge of Xenopus oocytes injected with EP1 cDNA
      resulted in an increase in intracellular Ca2+. In addition, the rank order of
      potency for prostaglandins in competition for [3H]PGE2 specific binding to
      membranes prepared from EP1 cDNA transfected COS cells was PGE2 > PGE1 > PGF2
      alpha > PGD2. Furthermore, the EP1 receptor-selective antagonists AH 6809 and
      SC19220 were more potent than the EP2 receptor-selective agonist butaprost in
      these competition binding assays. In summary, therefore, we have cloned the human
      EP1 receptor subtype which is functionally coupled to an increase in
      intracellular Ca2+.

PMID- 8253814
TI  - Alternative extracellular and cytoplasmic domains of the integrin alpha 7 subunit
      are differentially expressed during development.
AB  - Examination of cDNAs for the laminin-binding alpha 7 integrin subunit identified
      two different sequences (designated X1 and X2) coding for the variable region
      between the III and IV homology repeat domains near the putative ligand-binding
      site. Sequencing of a mouse alpha 7 genomic clone established that the X1 and X2
      regions are derived by mutually exclusive alternative mRNA splicing. Reverse
      transcriptase-polymerase chain reaction analysis of alpha 7 mRNA indicated that
      the X1 and X2 isoforms were present in equal amounts in mouse skeletal myoblasts
      and adult heart. However, in adult skeletal muscle, the X2 variant was
      exclusively expressed. Amino acid sequence homologies in the III/IV segment
      suggest that alpha 3 and alpha 6 are also alternatively spliced at this site. We
      identified alternatively spliced exons in a human alpha 6 genomic clone that
      encode X1- and X2-like segments. Analysis of the alpha 7 cytoplasmic domain
      indicated that this region was also alternatively spliced and like alpha 3 and
      alpha 6 could exist as the A or B form. In mouse skeletal and cardiac muscle the
      B form of alpha 7 was strongly expressed. However, we identified alpha 7A in
      neonate and adult skeletal muscle but not in cardiac tissue. High levels of alpha
      7A were detected in differentiating myotubes, but in proliferating myoblasts only
      the alpha 7B isoform was present. These results indicate that alternative
      splicing of alpha 7 mRNA is differentially regulated during development and
      generates variant integrin chains with structurally and presumably functionally
      unique ligand-binding and cytoplasmic domains.

PMID- 8253815
TI  - Heparin-binding peptides from thrombospondins 1 and 2 contain focal adhesion
      labilizing activity.
AB  - The cell adhesion regulating extracellular matrix glycoprotein, thrombospondin
      (TSP), causes a loss of focal adhesion plaques from spread endothelial cells and
      fibroblasts. To localize the site on TSP that has focal adhesion-labilizing
      activity, we initially tested proteolytic fragments of TSP for activity. The
      heparin-binding fragment has significant focal adhesion-labilizing activity,
      whereas the nonheparin-binding 140-kDa fragment had no significant activity.
      These results were consistent with previous data that showed that both a
      monoclonal antibody to the heparin-binding domain of TSP (A2.5) and heparin
      neutralized TSP activity. Peptides from putative heparin binding sequences of the
      amino-terminal heparin-binding domain of TSP were synthesized and tested for
      their ability to cause loss of focal adhesions. The hep I peptide (amino acids 17
      35) caused maximal loss of focal adhesions and was active at 0.1 microM, whereas
      peptide hep II (74-95) and peptide hep III (170-189) were inactive. The activity
      of the hep I peptide was neutralized by the addition of heparin and heparan
      sulfate but not by chondroitin sulfate. The basic amino acids in the hep I
      sequence appear to be required for focal adhesion-labilizing activity, because
      modification of the lysine residues at amino acids 24 and 32 rendered the peptide
      completely inactive. In addition, a peptide from the analogous sequence of mouse
      TSP 2, in which basic residues are conserved, was nearly as active as hep I from
      TSP1. These data show that the anti-adhesive activity of TSP is conserved in both
      TSP1 and TSP2 and that the active site is located in a 19-amino acid sequence in
      the heparin-binding domain of TSPs.

PMID- 8253816
TI  - Identification of a new serine kinase that activates NF kappa B by direct
      phosphorylation.
AB  - A novel serine kinase, named nuclear factor kappa B (NF kappa B) kinase, has been
      shown to be associated with the NF kappa B.I kappa B complex in the cytosol of
      human primary T lymphocytes. It activates the DNA binding activity of NF kappa B
      by directly phosphorylating its p65 and p50 subunits. There is no evidence that
      it phosphorylates I kappa B. Experiments with inhibitors and antisera showed that
      it is distinct from other known serine kinases such as mitogen-activated protein
      kinase or Mos. It has an apparent molecular size of 43 kDa determined by the
      substrate binding assay. This kinase might have a central role in mediating
      various signals to NF kappa B.

PMID- 8253817
TI  - Thrombin-induced phosphorylation and activation of Ca(2+)-sensitive cytosolic
      phospholipase A2 in human platelets.
AB  - Receptor-mediated activation of human platelets by thrombin initiates a series of
      rapid biochemical events that include activation of phospholipase A2 to liberate
      arachidonic acid for further conversion to thromboxane A2. The identity of the
      phospholipase A2 involved has not been clear. Here we show by immunochemical
      analysis that human platelets contain significant amounts (60 ng/10(9) platelets)
      of the recently identified Ca(2+)-sensitive cytosolic phospholipase A2 (cPLA2).
      Metabolic labeling of human platelets with 33Pi revealed that the extent of
      phosphorylation of cPLA2 was greatly increased after thrombin treatment. Upon
      stimulation of platelets with thrombin, cPLA2 exhibits enhanced catalytic
      activity, as well as a change in its electrophoretic and chromatographic
      properties compared with cPLA2 in resting platelets. These alterations of cPLA2
      are reversed by treatment with phosphatase, demonstrating that they are the
      consequence of thrombin-stimulated phosphorylation. Thrombin-induced
      phosphorylation and activation of cPLA2 is rapid (half-maximal by 1 min at 1
      unit/10(9) platelets) and dose-dependent. Agonist-induced phosphorylation of
      cPLA2 is more sensitive to thrombin than the generation of thromboxane A2,
      suggesting that it may be an early event in the sequence of steps leading to the
      mobilization and further metabolism of arachidonic acid. By comparing the
      functional properties of cPLA2 from control versus thrombin-stimulated platelets,
      we found that while activated cPLA2 exhibits the same Ca2+ requirement and
      apparent substrate affinity (Km), its catalytic activity (Vmax) is increased
      compared with control cPLA2. We conclude that 1) cPLA2 is likely to play an
      important role in agonist-induced mobilization of arachidonic acid and 2)
      thrombin elicits rapid and full activation of cPLA2 not only by promoting a rise
      in cytosolic free Ca2+ but also by inducing phosphorylation of cPLA2 thereby
      improving its catalytic activity.

PMID- 8253818
TI  - Differential induction of nuclear NF-kappa B by protein phosphatase inhibitors in
      primary and transformed human cells. Requirement for both oxidation and
      phosphorylation in nuclear translocation.
AB  - Phosphoseryl/threonyl protein phosphatase inhibitors, viz. okadaic acid and
      calyculin-A, failed to induce nuclear factor-kappa B (NF-kappa B) nuclear
      translocation in several primary human cells although a marked and rapid
      induction was observed in their simian virus 40 transformed counterparts.
      Inability to induce NF-kappa B cannot be due to a non-activatable system since NF
      kappa B was strongly activated by tumor necrosis factor in all the five primary
      cell types tested. It is also unlikely that the differential induction was due to
      differential sensitivity of primary and transformed cells to phosphatase
      inhibitors as the intracellular phosphatase activities of both cell types were
      equally inhibited by these inhibitors. However, pretreatment with hydrogen
      peroxide or buthionine sulfoximine, chemicals known to directly or indirectly
      elevate the intracellular free-radical levels, enabled okadaic acid to induce
      nuclear translocation of NF-kappa B in primary cells. Conversely cysteine, an
      antioxidant and precursor of the free radical scavenger, glutathione, inhibited
      the induction of NF-kappa B by tumor necrosis factor in primary cells, and by
      okadaic acid or tumor necrosis factor in transformed cells. These data, taken
      together, suggest that free radical-dependent oxidation and protein
      phosphorylation are not independent modes of NF-kappa B induction, but are both
      required for the release of NF-kappa B from I kappa B. Furthermore, the
      differential induction of NF-kappa B nuclear translocation by okadaic acid in
      primary and transformed human cells, reported herein, reflects intrinsic
      differences in the intracellular oxidative state between the two groups of cells.
      The induction of NF-kappa B by tumor necrosis factor in primary cells suggests
      that this cytokine fulfills the requirement for oxidation, possibly by inducing
      the production of free radicals.

PMID- 8253819
TI  - The role of synovial fluid filtration by cartilage in lubrication of synovial
      joints--I. Mixture model of synovial fluid.
AB  - A mathematical model of lubrication of human synovial joints under squeeze-film
      conditions is presented in this several-part paper. Squeeze-film action leads to
      a concentration of hyaluronic-acid-protein macromolecular complex in the synovial
      fluid between the approaching cartilage surfaces as a result of the diffusion of
      water and low molecular weight substances through the cartilage surfaces or along
      the gap. Increasing viscosity of synovial fluid delays the approach of these
      surfaces and the formation of stable gels then protects cartilage, if sliding
      motion ensues, before fluid film lubrication is restored. In Part I of the
      present paper synovial fluid is considered as a mixture of two incompressible
      fluids. The material parameters of this mixture of fluids are found using
      previously published experimental results. Squeeze-film analysis is carried out
      for the axially symmetric synovial film.

PMID- 8253820
TI  - The role of synovial fluid filtration by cartilage in lubrication of synovial
      joints--II. Squeeze-film lubrication: homogeneous filtration.
AB  - A mathematical model of synovial film filtration and synovial gel formation at
      normal approach of cartilage surfaces in the human hip joint is presented. The
      biphasic mixture model presented in Part I of this paper [Hlavacek, J.
      Biomechanics 26, (1993)] for synovial fluid and that of Mow and his collaborators
      [J. Biomech. Engng 102, 73-84 (1980)] for cartilage are used. A general analysis
      of filtration of an axially symmetric synovial squeeze-film between two cartilage
      layers at normal approach is given. The geometrically simple case much idealising
      the human hip joint is also considered: two cartilage discs with a synovial film
      in between are compressed by the steady loading of the half human weight. The
      homogeneous film filtration process where the synovial gap remains parallel and
      the macromolecular concentration in the gap is spatial homogeneous (to the thin
      film approximation) and time-dependent is numerically analysed. If the hyaluronic
      acid concentration of the synovial gel at equilibrium is 50 mg/ml at least, the
      resulting stable gel layer thickness for the homogeneous filtration in the human
      hip joint and for normal synovial fluids is about 0.1 micron, being almost
      independent of the loading. Inflammatory synovial fluid shows values several
      times lower.

PMID- 8253821
TI  - Numerical analysis of pulmonary indicator gas wash-in.
AB  - Mathematical modelling of gas transport in the human lung yields a diffusion
      convection problem. Transport is described by a second-order parabolic partial
      differential equation with variable coefficients and initial and boundary
      conditions. A new numerical approach for the solution of these governing
      equations is proposed in which the convection term is dealt with exactly. This
      method combines integration along characteristics and the finite difference
      method. The results obtained are in agreement with those of other investigators
      but are based on less stringent assumptions. To judge the merit of various finite
      difference schemes, the results are compared with analytical solutions for a
      special case in which the lung is modelled as a uniform cylinder. Laplace
      transform techniques and expansion into Fourier series are used to obtain the
      analytical solutions.

PMID- 8253822
TI  - The hand of the musician: the kinematics of the bidigital finger system with
      anatomical restrictions.
AB  - Tendons of the fingers are frequently interconnected by anatomic structures that
      limit the displacements of these tendons relative to each other. In this paper a
      bidigital finger system in which such interconnections between tendons are
      present is kinematically modelled. Using this model, an exhaustive description of
      the effects on finger movement of connections between the different tendons of
      the fingers is given. The study provides a context for the interpretation of
      typical difficulties of finger coordination in musicians, especially in pianists
      and string players.

PMID- 8253823
TI  - Do postural responses to transient and continuous perturbations show similar
      vision and amplitude dependence?
AB  - This study compares the influence of vision and perturbation amplitude on
      postural center-of-pressure responses to transient (acceleration pulse) versus
      continuous (pseudorandom acceleration) platform-translation perturbations. To
      control possible confounding effects, efforts were directed at making the
      perturbations unpredictable and matching the transient and continuous waveforms
      in terms of frequency content and level of challenge to stability. It was
      hypothesized that, under these conditions, the same control mechanisms would be
      activated; hence, responses to transient and continuous perturbations would show
      similar vision and amplitude dependence. A repeated-measures experimental design
      was used to test 12 healthy males. The transient and continuous perturbations
      were each administered at three acceleration amplitude levels, in random order,
      and the tests were repeated under eyes-open and blindfolded conditions. When
      order-of-testing effects were taken into account, the results failed to
      demonstrate any differences between transient and continuous postural control
      with regard to the influence of vision, as both types of response were unaffected
      by vision deprivation. This finding is consistent with the experimental
      hypothesis. Responses to the two types of perturbation did appear to differ,
      however, with regard to the influence of perturbation amplitude, as the transient
      perturbation responses showed greater evidence of nonlinearity. This finding
      would seem to reject the hypothesis that the responses to transient and
      continuous perturbations would show similar amplitude dependence. However, it is
      suggested that the amplitude distribution of the particular continuous waveform
      that was used, rather than the continuous nature of the perturbation per se, may
      have led to the greater linearity in the continuous-perturbation responses.
      Although the present results fail to provide unequivocal support for the
      hypothesis that the same control mechanisms are utilized in transient and
      continuous balance recovery, they do demonstrate that distinctions between these
      two types of postural task are not nearly so clearcut as has been suggested.
      Nonetheless, from a practical perspective, the findings of substantial
      nonlinearity indicate that attempts to predict responses to transient
      perturbations from continuous-perturbation tests should be performed with
      caution.

PMID- 8253824
TI  - Dynamics of below-knee child amputee gait: SACH foot versus Flex foot.
AB  - Gait kinematics and dynamics during stance of unilateral, below-knee child
      amputees were analyzed for self-selected, comfortable (0.9 m s-1) and fast (1.3 m
      s-1) speeds with the SACH foot and the energy-storing Flex-foot prostheses. The
      three-dimensional movements of the lower limbs were recorded and synchronized
      with ground reaction forces for 12 subjects (7 girls and 5 boys, ages 6-16 yr).
      Each lower limb was modeled as a set of interconnected rigid links (thigh, leg,
      and foot) with frictionless joints (hip, knee, and ankle) to calculate moment and
      joint power profiles. Marked asymmetries were noted in ground reaction force,
      joint moment, and power profiles for the prosthetic versus the natural limb, but
      with the Flex foot the asymmetries were less pronounced than with the SACH foot.
      For the amputee wearing the Flex foot, greater moments and power were generated
      by the natural limb at the comfortable pace as compared to the SACH foot, but
      during fast walking, the SACH foot required greater output from the natural limb.
      With both prostheses, for the prosthetic limb the amputees used similar force,
      moment, and power patterns, but with significantly different amplitudes. At both
      speeds of walking, the Flex foot returned significantly more energy (66% at
      comfortable and 70% at fast walking) than the SACH foot (21% at comfortable and
      19% at fast walking). Thus, the Flex foot had a greater potential for reducing
      the energy cost of walking at comfortable and fast speeds for the below-knee
      child amputee.

PMID- 8253825
TI  - Effects of porous coating and collar support on early load transfer for a
      cementless hip prosthesis.
AB  - We used a new postprocessing method with the results from a three-dimensional
      finite element analysis to describe the general load transfer patterns for a
      cementless hip arthroplasty in the early postoperative situation, and to
      determine the effects of porous coating [full, partial (2/3), and none] and
      calcar-collar support (ideal initial contact with separation allowed upon
      loading, no collar) on this early load transfer. No-tension interfaces were
      modeled over the entire bone-prosthesis interface, with an upper bound on the
      Coulomb-friction over coated surfaces, and zero friction over smooth surfaces to
      accentuate the frictional effects of the coating. The results indicate that the
      anteroposterior, mediolateral, and axial forces acting on each cross section of
      the bone were substantially different from the corresponding homeostatic (no
      prosthesis) forces for the fully coated device with collar support. The frontal
      bending moments acting on the bone were substantially less than the homeostatic
      values all along the prosthesis, while the sagittal bending and torsional loads
      were relatively similar to the homeostatic values. By far, the largest change in
      these loading patterns occurred with the loss of collar support, where axial
      loads acting on the bone were so low that over half the bone was in net tension
      because appreciable transfer of the compressive head force did not occur until
      well below the lesser trochanter. Both axial and torsional loads were transferred
      more distally for devices with more coating, and torsional loading of the bone
      was also sensitive to the degree of collar support. The frontal bending moments
      acting over most of the bone were insensitive to the coating or collar support.
      The strain energy density in the endosteal bone was most sensitive to these
      design variables in the proximal region, and the largest values occurred without
      a collar and without coating. These findings indicate that all load components
      acting on the proximal bone in the early postoperative situation (no bone
      ingrowth or fibrous tissue at the interface) are altered by the frictional
      coefficient of the bone-prosthesis interface (i.e. the presence of porous coating
      or some other surface treatment) and the degree of collar support, while only the
      axial and torsional loads are altered in the distal bone. From a prosthesis
      design perspective this implies that surface treatments and collar support can be
      used to control the axial forces and the torsional moments acting all along the
      bone. By contrast, the distal frontal bending moment, which dominates stresses in
      the diaphysis, cannot be altered by these design variables.

PMID- 8253826
TI  - Comparison of the cardiac force-time integral with energetics using a cardiac
      muscle model.
AB  - Several investigators have found experimentally that the force-time integral
      varies non-linearly with energy expenditure over the course of a cardiac
      contraction. Also, recent research findings have indicated that the crossbridge
      cycle to ATP hydrolysis ratio in muscle fiber systems may not be coupled with a
      one-to-one ratio. In order to investigate these findings, Huxley's sliding
      filament crossbridge muscle model coupled with parallel and series elastic
      components was simulated to examine the behavior of the crossbridge energy
      utilization and force-time integral vs time. Crossbridge (CB) energy utilization
      was determined by considering the ATP hydrolysis for the crossbridge cycling, and
      this CB energy was compared with the force-length energy in a contraction. This
      CB energy was calculated in both isometric and isotonic contractions as a
      function of contraction time and compared to the force-time integral. Simulation
      results demonstrated that the ratio of the force-time integral to CB energy
      varies strongly throughout the cardiac cycle for both isometric and isotonic
      cases, as has been observed experimentally. Simulations also showed that using
      the force-length energy component of energy vs the CB energy gave a better
      correlation between the total energetic predictions and the force-time integral,
      agreeing with recent finding that the crossbridge cycle to ATP hydrolysis ratio
      may not be coupled one-to-one, especially at lower force levels.

PMID- 8253827
TI  - A method for studying the biomechanical load response of the (in vitro) lumbar
      spine under dynamic flexion-shear loads.
AB  - A method was developed to study the biomechanical response of the lumbar motion
      segment (Functional Spinal Unit, FSU) under a dynamic (transient) load in
      flexion. In order to inflict flexion-distraction types of injuries (lap seat-belt
      injuries) different load pulses were transferred to the specimen by means of a
      padded pendulum. The load response of the specimen was measured with a force and
      moment transducer. The flexion angulation and displacements were determined by
      means of high-speed photography. Two series of tests were made with ten specimens
      in each and with two different load pulses: one moderate load pulse (peak
      acceleration 5 g, rise time 30 ms, duration 150 ms) and one severe load pulse
      (peak acceleration 12 g, rise time 15 ms, duration 250 ms). The results showed
      that the moderate load pulse caused residual permanent deformations at a mean
      bending moment of 140 Nm and a mean shear force of 430 N at a mean flexion
      angulation of 14 degrees. The severe load pulse caused evident signs of failure
      of the segments at a mean bending moment of 185 Nm and a mean shear force of 600
      N at a mean flexion angulation of 19 degrees. Significant correlations were found
      between the load response and the size of the specimen, as well as between the
      load response and the bone mineral content (BMC) in the two adjacent vertebrae.
      Comparisons with lumbar spine response to static flexion-shear loading indicated
      that the specimens could withstand higher bending moments before injury occurred
      during dynamic loading, but the deformations at injury tended to be smaller for
      dynamic loading.

PMID- 8253828
TI  - Two-dimensional velocity measurements in a pulsatile flow model of the normal
      abdominal aorta simulating different hemodynamic conditions.
AB  - The infrarenal abdominal aorta and aortic bifurcation are frequent sites of
      atherosclerosis. The local hemodynamics are considered to be an atherogenetic
      factor, and a detailed description of the flow fields in this region of the
      arterial tree is therefore essential. The aim of this study was to provide
      quantitative two-dimensional data on the velocity fields in the abdominal aorta,
      using a realistic flow model of the abdominal aorta and its main branches, under
      various physiologic flow conditions (i.e. rest and exercise). Velocities in the
      suprarenal abdominal aorta were antegrade, with very little retrograde and radial
      velocity components present. In the infrarenal abdominal aorta, velocity profiles
      were not fully developed, and large-scale retrograde flow was present during part
      of diastole for the rest condition. For the exercise conditions small-scale
      retrograde velocities were present during diastole, especially at the distal
      posterior vessel wall, but not at the distal anterior vessel wall. For the rest
      and medium exercise conditions, secondary flows were created in the distal
      abdominal aorta during diastole, most prominent near the posterior wall.
      Calculated wall shear stress directions revealed the presence of both oscillatory
      and multidirectional wall shear stresses mainly in parts of the infrarenal
      abdominal aorta, and were found to correlate well with the published data on the
      distribution of early atherosclerotic lesions. This quantitative study
      demonstrates the necessity of carefully modeling both the anatomy and the
      physiology in order to understand the complex hemodynamics present in the
      abdominal aorta.

PMID- 8253829
TI  - The effect of different storage methods on the mechanical properties of
      trabecular bone.
AB  - The effect of different storage methods on the elastic and viscoelastic
      properties of trabecular bone was examined using non-destructive compression
      tests to 0.45% specimen strain. There was a 10% decrease in stiffness during the
      first 24 h post mortem. Storage by freezing or in ethanol for 100 d did not
      change the stiffness, and neither did several thawing, testing and refreezing
      sequences. The viscoelastic properties were more sensitive to storage and showed
      significant although small changes during 100 d of storage. The effect of
      defatting the specimens was a 30% increase in stiffness and a 50% decrease in
      viscoelastic energy dissipation.

PMID- 8253830
TI  - Development of linear and nonlinear hand-arm vibration models using optimization
      and linearization techniques.
AB  - Hand-arm vibration (HAV) models serve as an effective tool to assess the
      vibration characteristics of the hand-tool system and to evaluate the attenuation
      performance of vibration isolation mechanisms. This paper describes a methodology
      to identify the parameters of HAV models, whether linear or nonlinear, using
      mechanical impedance data and a nonlinear programming based optimization
      technique. Three- and four-degrees-of-freedom (DOF) linear, piecewise linear and
      nonlinear HAV models are formulated and analyzed to yield impedance
      characteristics in the 5-1000 Hz frequency range. A local equivalent
      linearization algorithm, based upon the principle of energy similarity, is
      implemented to simulate the nonlinear HAV models. Optimization methods are
      employed to identify the model parameters, such that the magnitude and phase
      errors between the computed and measured impedance characteristics are minimum in
      the entire frequency range. The effectiveness of the proposed method is
      demonstrated through derivations of models that correlate with the measured X
      axis impedance characteristics of the hand-arm system, proposed by ISO. The
      results of the study show that a linear model cannot predict the impedance
      characteristics in the entire frequency range, while a piecewise linear model
      yields an accurate estimation.

PMID- 8253831
TI  - The erythropoietin receptor: its role in hematopoiesis and myeloproliferative
      diseases.

PMID- 8253833
TI  - Determination of initiation of DNA replication before and after nuclear formation
      in Xenopus egg cell free extracts.
AB  - Xenopus egg extracts prepared before and after egg activation retain M- and S
      phase specific activity, respectively. Staurosporine, a potent inhibitor of
      protein kinase, converted M-phase extracts into interphase-like extracts that
      were capable of forming nuclei upon the addition of sperm DNA. The nuclei formed
      in the staurosporine treated M-phase extract were incapable of replicating DNA,
      and they were unable to initiate replication upon the addition of S-phase
      extracts. Furthermore, replication was inhibited when the staurosporine-treated M
      phase extract was added in excess to the staurosporine-treated S-phase extract
      before the addition of DNA. The membrane-depleted S-phase extract supported
      neither nuclear formation nor replication; however, preincubation of sperm DNA
      with these extracts allowed them to form replication-competent nuclei upon the
      addition of excess staurosporine-treated M-phase extract. These results
      demonstrate that positive factors in the S-phase extracts determined the
      initiation of DNA replication before nuclear formation, although these factors
      were unable to initiate replication after nuclear formation.

PMID- 8253832
TI  - Eukaryotic initiation factor 5A is a cellular target of the human
      immunodeficiency virus type 1 Rev activation domain mediating trans-activation.
AB  - Expression of human immunodeficiency virus type 1 (HIV-1) structural proteins
      requires the presence of the viral trans-activator protein Rev. Rev is localized
      in the nucleus and binds specifically to the Rev response element (RRE) sequence
      in viral RNA. Furthermore, the interaction of the Rev activation domain with a
      cellular cofactor is essential for Rev function in vivo. Using cross-linking
      experiments and Biospecific Interaction Analysis (BIA) we identify eukaryotic
      initiation factor 5A (eIF-5A) as a cellular factor binding specifically to the
      HIV-1 Rev activation domain. Indirect immunofluorescence studies demonstrate that
      a significant fraction of eIF-5A localizes to the nucleus. We also provide
      evidence that Rev transactivation is functionally mediated by eIF-5A in Xenopus
      oocytes. Furthermore, we are able to block Rev function in mammalian cells by
      antisense inhibition of eIF-5A gene expression. Thus, regulation of HIV-1 gene
      expression by Rev involves the targeting of RRE-containing RNA to components of
      the cellular translation initiation complex.

PMID- 8253834
TI  - Intranuclear filaments containing a nuclear pore complex protein.
AB  - Nuclear pore complexes (NPCs) are anchoring sites of intranuclear filaments of 3
      6 nm diameter that are coaxially arranged on the perimeter of a cylinder and
      project into the nuclear interior for lengths varying in different kinds of
      cells. Using a specific monoclonal antibody we have found that a polypeptide of
      approximately 190 kD on SDS-PAGE, which appears to be identical to the recently
      described NPC protein "nup 153," is a general constituent of these intranuclear
      NPC-attached filaments in different types of cells from diverse species,
      including amphibian oocytes where these filaments are abundant and can be
      relatively long. We have further observed that during mitosis this filament
      protein transiently disassembles, resulting in a distinct soluble molecular
      entity of approximately 12.5 S, and then disperses over most of the cytoplasm.
      Similarly, the amphibian oocyte protein appears in a soluble form of
      approximately 16 S during meiotic metaphase and can be immunoprecipitated from
      egg cytoplasmic supernatants. We conclude that this NPC protein can assemble into
      a filamentous form at considerable distance from the nuclear envelope and discuss
      possible functions of these NPC-attached filaments, from a role as guidance
      structure involved in nucleocytoplasmic transport to a form of excess storage of
      NPC proteins in oocytes.

PMID- 8253835
TI  - Nup180, a novel nuclear pore complex protein localizing to the cytoplasmic ring
      and associated fibrils.
AB  - Using an autoimmune serum from a patient with overlap connective tissue disease
      we have identified by biochemical and immunocytochemical approaches an
      evolutionarily conserved nuclear pore complex (NPC) protein with an estimated
      molecular mass of 180 kD and an isoelectric point of approximately 6.2 which we
      have designated as nup180. Extraction of isolated nuclear envelopes with 2 M urea
      and chromatography of the solubilized proteins on WGA-Sepharose demonstrated that
      nup180 is a peripheral membrane protein and does not react with WGA. Affinity
      purified antibodies yielded a punctate immunofluorescent pattern of the nuclear
      surface of mammalian cells and stained brightly the nuclear envelope of
      cryosectioned Xenopus oocytes. Nuclei reconstituted in vitro in Xenopus egg
      extract were also stained in the characteristic punctate fashion. Immunogold EM
      localized nup180 exclusively to the cytoplasmic ring of NPCs and short fibers
      emanating therefrom into the cytoplasm. Antibodies to nup180 did not inhibit
      nuclear protein transport in vivo nor in vitro. Despite the apparent lack of
      involvement in NPC assembly or nucleocytoplasmic transport processes, the
      conservation of nup180 across species and its exclusive association with the NPC
      cytoplasmic ring suggests an important, though currently undefined function for
      this novel NPC protein.

PMID- 8253836
TI  - A Sec63p-BiP complex from yeast is required for protein translocation in a
      reconstituted proteoliposome.
AB  - Reconstituted proteoliposomes derived from solubilized yeast microsomes are able
      to translocate a secreted yeast mating pheromone precursor (Brodsky, J. L., S.
      Hamamoto, D. Feldheim, and R. Schekman. 1993. J. Cell Biol. 120:95-107).
      Reconstituted proteoliposomes prepared from strains with mutations in the SEC63
      or KAR2 genes are defective for translocation; the kar2 defect can be overcome by
      the addition of purified BiP (encoded by the KAR2 gene). We now show that
      addition of BiP to wild-type reconstituted vesicles increases their translocation
      efficiency three-fold. To identify other ER components that are required for
      translocation, we purified a microsomal membrane protein complex that contains
      Sec63p. We found that the complex also includes BiP, Sec66p (gp31.5), and Sec67p
      (p23). The Sec63p complex restores translocation activity to reconstituted
      vesicles that are prepared from a sec63-1 strain, or from cells in which the
      SEC66 or SEC67 genes are disrupted. BiP dissociates from the complex when the
      purification is performed in the presence of ATP gamma S or when the starting
      membranes are from yeast containing the sec63-1 mutation. We conclude that the
      purified Sec63p complex is active and required for protein translocation, and
      that the association of BiP with the complex may be regulated in vivo.

PMID- 8253837
TI  - Hydrolysis of bound GTP by ARF protein triggers uncoating of Golgi-derived COP
      coated vesicles.
AB  - The cycle of nucleotide exchange and hydrolysis by a small GTP-binding protein,
      ADP-ribosylation factor (ARF), helps to provide vectoriality to vesicle
      transport. Coat assembly is triggered when ARF binds GTP, initiating transport
      vesicle budding, and coat disassembly is triggered when ARF hydrolyzes GTP,
      allowing the uncoated vesicle to fuse.

PMID- 8253838
TI  - Cytoplasmic dynein-dependent vesicular transport from early to late endosomes.
AB  - We have used an in vitro fusion assay to study the mechanisms of transport from
      early to late endosomes. Our data show that the late endosomes share with the
      early endosomes a high capacity to undergo homotypic fusion in vitro. However,
      direct fusion of early with late endosomes does not occur. We have purified
      vesicles which are intermediates during transport from early to late endosomes in
      vivo, and analyzed their protein composition in two-dimensional gels. In contrast
      to either early or late endosomes, these vesicles do not appear to contain unique
      proteins. Moreover, these vesicles undergo fusion with late endosomes in vitro,
      but not with each other or back with early endosomes. In vitro, fusion of these
      endosomal vesicles with late endosomes is stimulated by polymerized microtubules,
      consistent with the known role of microtubules during early to late endosome
      transport in vivo. In contrast, homotypic fusion of early or late endosomes is
      microtubule-independent. Finally, this stimulation by microtubules depends on
      microtubule-associated proteins and requires the presence of the minus-end
      directed motor cytoplasmic dynein, but not the plus-end directed motor kinesin,
      in agreement with the microtubule organization in vivo. Our data strongly suggest
      that early and late endosomes are separate, highly dynamic organelles, which are
      connected by a microtubule-dependent vesicular transport step.

PMID- 8253839
TI  - Beta-very low density lipoprotein is sequestered in surface-connected tubules in
      mouse peritoneal macrophages.
AB  - beta-very low density lipoprotein (VLDL) is a large lipoprotein with multiple
      apoprotein E (apoE) molecules that bind to the LDL receptors on mouse
      macrophages. Even though they bind to the same receptor, the endocytic processing
      of beta-VLDL differs from low density lipoprotein (LDL). LDL is rapidly delivered
      to perinuclear lysosomes and degraded, but much of the beta-VLDL is retained in
      peripheral compartments for several minutes. We have investigated the properties
      of these peripheral compartments. Measurement of the pH was made using FITC
      phosphatidylethanolamine incorporated into the beta-VLDL, and we found that the
      peripheral compartments were near neutral in pH. These peripheral, beta-VLDL
      containing compartments were poorly accessible to antibodies, but a low molecular
      weight fluorescence quencher (trypan blue) entered the compartments within a few
      seconds. Intermediate voltage EM of cells labeled with colloidal-gold-beta-VLDL
      revealed that the peripheral compartments are tubular, surface-connected
      invaginations. Kinetic studies with fluorescent beta-VLDL showed that the
      compartments become fully sealed with a half-time of 6 min, and the beta-VLDL is
      then delivered rapidly to perinuclear lysosomes. By monitoring fluorescence
      energy transfer between lipid analogs incorporated into the beta-VLDL, some
      processing of the lipoprotein in the peripheral tubular compartments is
      demonstrated. The novel mode of uptake of beta-VLDL may account for the high
      cholesterol ester accumulation induced by this lipoprotein.

PMID- 8253840
TI  - Retrograde lipid traffic in yeast: identification of two distinct pathways for
      internalization of fluorescent-labeled phosphatidylcholine from the plasma
      membrane.
AB  - Digital, video-enhanced fluorescence microscopy and spectrofluorometry were used
      to follow the internalization into the yeast Saccharomyces cerevisiae of
      phosphatidylcholine molecules labeled on one acyl chain with the fluorescent
      probe 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD). Two pathways were found: (1)
      transport by endocytosis to the vacuole and (2) transport by a non-endocytic
      pathway to the nuclear envelope and mitochondria. The endocytic pathway was
      inhibited at low temperature (< 2 degrees C) and by ATP depletion. Mutations in
      secretory (SEC) genes that are necessary for membrane traffic through the
      secretory pathway (including SEC1, SEC2, SEC4, SEC6, SEC7, SEC12, SEC14, SEC17,
      SEC18, and SEC21) almost completely blocked endocytic uptake. In contrast,
      mutations in the SEC63, SEC65, or SEC11 genes, required for translocation of
      nascent secretory polypeptides into the ER or signal peptide processing in the
      ER, only slightly reduced endocytic uptake. Phospholipid endocytosis was also
      independent of the gene encoding the clathrin heavy chain, CHC1. The correlation
      of biochemical analysis with fluorescence microscopy indicated that the
      fluorescent phosphatidylcholine was degraded in the vacuole and that degradation
      was, at least in part, dependent on the vacuolar proteolytic cascade. The non
      endocytic route functioned with a lower cellular energy charge (ATP levels 80%
      reduced) and was largely independent of the SEC genes. Non-endocytic transport of
      NBD-phosphatidylcholine to the nuclear envelope and mitochondria was inhibited by
      pretreatment of cells with the sulfhydryl reagents N-ethylmaleimide and p
      chloromercuribenzenesulfonic acid, suggesting the existence of protein-mediated
      transmembrane transfer (flip-flop) of phosphatidylcholine across the yeast plasma
      membrane. These data establish a link between lipid movement during secretion and
      endocytosis in yeast and suggest that phospholipids may also gain access to
      intracellular organelles through non-endocytic, protein-mediated events.

PMID- 8253841
TI  - Mechanisms of urinary K+ and H+ excretion: primary structure and functional
      expression of a novel H,K-ATPase.
AB  - The kidney plays an essential role in regulating potassium and acid balance. A
      major site for these regulations is in the collecting tubule. In the present
      study, we report the primary sequence of a novel alpha subunit of the P-ATPase
      gene family, which we isolated from the urinary bladder epithelium of the toad
      Bufo marinus, the amphibian equivalent of the mammalian collecting tubule. The
      cDNA encodes a protein of 1,042 amino acids which shares approximately 67%
      identity with the alpha 1 subunit of the ouabain-inhibitable Na,K-ATPase and
      approximately 69% identity with the alpha subunit of the SCH28080-inhibitable
      gastric H,K-ATPase. When coexpressed in Xenopus oocytes with a beta subunit
      isolated from the same cDNA library, the ATPase is able to transport rubidium (a
      potassium surrogate) inward, and hydrogen outward, leading to alkalization of the
      intracellular compartment and acidification of the external medium. The novel
      ATPase has a unique pharmacological profile showing intermediate sensitivity to
      both ouabain and SCH28080. Our findings indicate that the bladder ATPase is a
      member of a new ion motive P-ATPase subfamily. The bladder ATPase is expressed in
      the urinary tract but not in the stomach or the colon. This H,K-ATPase may be one
      of the molecules involved in H+ and K+ homeostasis, mediating the transport of
      these ions across urinary epithelia and therefore regulating their urinary
      excretion.

PMID- 8253842
TI  - Egg cortical granule N-acetylglucosaminidase is required for the mouse zona block
      to polyspermy.
AB  - The mammalian egg must be fertilized by only one sperm to prevent polyploidy. In
      most mammals studied to date, the primary block to polyspermy occurs at the zona
      pellucida, the mammalian egg coat, after exocytosis of the contents of the
      cortical granules into the perivitelline space. The exudate acts on the zona,
      causing it to lose its ability to bind sperm and to be penetrated by sperm
      previously bound to the zona. However, the cortical granule components
      responsible for the zona block have not been identified. Studies described herein
      demonstrate that N-acetylglucosaminidase is localized in cortical granules and is
      responsible for the loss in sperm-binding activity leading to the zona block to
      polyspermy. Before fertilization, sperm initially bind to the zona by an
      interaction between sperm surface GalTase and terminal N-acetylglucosamine
      residues on specific oligosaccharides of the zona glycoprotein ZP3 (Miller, D.
      J., M. B. Macek, and B. D. Shur. 1992. Nature (Lond.). 357:589-593). These
      GalTase-binding sites are lost from ZP3 after fertilization, an effect that can
      be duplicated by N-acetylglucosaminidase treatment. Therefore, N
      acetylglucosaminidase, or a related glycosidase, may be present in cortical
      granules and be responsible for ZP3's loss of sperm-binding activity at
      fertilization. Of eight glycosidases assayed in exudates of ionophore-activated
      eggs, N-acetylglucosaminidase was 10-fold higher than any other activity. The
      enzyme was localized to cortical granules using immunoelectron microscopy.
      Approximately 70 or 90% of the enzyme was released from cortical granules after
      ionophore activation or in vivo fertilization, respectively. The isoform of N
      acetylglucosaminidase found in cortical granules was identified as beta
      hexosaminidase B, the beta, beta homodimer. Inhibition of N-acetylglucosaminidase
      released from activated eggs, with either competitive inhibitors or with specific
      antibodies, resulted in polyspermic binding to the zona pellucida. Another
      glycosidase inhibitor or nonimmune antibodies had no effect on sperm binding to
      activated eggs. Therefore, egg cortical granule N-acetylglucosaminidase is
      released at fertilization, where it inactivates the sperm GalTase-binding site,
      accounting for the block in sperm binding to the zona pellucida.

PMID- 8253843
TI  - Olfactory receptors are displayed on dog mature sperm cells.
AB  - Olfactory receptors constitute a huge family of structurally related G protein
      coupled receptors, with up to a thousand members expected. We have shown
      previously that genes belonging to this family were expressed in the male germ
      line from both dog and human. The functional significance of this unexpected site
      of expression was further investigated in the present study. We demonstrate that
      a few dog genes representative of various subfamilies of olfactory receptors are
      expressed essentially in testis, with little or no expression in olfactory
      mucosa. Other randomly selected members of the family show the expected site of
      expression, restricted to the olfactory system. Antibodies were generated against
      the deduced amino acid sequence of the most abundantly expressed olfactory
      receptor gene in dog testis. The purified serum was able to detect the gene
      product (DTMT receptor) in late round and elongated spermatids, as well as in the
      cytoplasmic droplet that characterizes the maturation of dog sperm cells, and on
      the tail midpiece of mature spermatozoa. Western blotting further confirmed the
      presence of a 40-kD immunoreactive protein in the membrane of mature sperm cells.
      Altogether , these results demonstrate that the main expression site of a subset
      of the large olfactory receptor gene family is not olfactory mucosa but testis.
      This expression correlates with the presence of the corresponding protein during
      sperm cell maturation, and on mature sperm cells. The pattern of expression is
      consistent with a role as sensor for unidentified chemicals possibly involved in
      the control of mammalian sperm maturation, migration, and/or fertilization.

PMID- 8253844
TI  - 440-kD ankyrinB: structure of the major developmentally regulated domain and
      selective localization in unmyelinated axons.
AB  - 440-kD ankyrinB is an alternatively spliced variant of 220-kD ankyrinB, with a
      predicted 220-kD sequence inserted between the membrane/spectrin binding domains
      and COOH-terminal domain (Kunimoto, M., E. Otto, and V. Bennett. 1991. J. Cell
      Biol. 236:1372-1379). This paper presents the sequence of 2085 amino acids
      comprising the alternatively spliced portion of 440-kD ankyrinB, and provides
      evidence that much of the inserted sequence has the configuration of an extended
      random coil. Notable features of the inserted sequence include a hydrophilicity
      profile that contains few hydrophobic regions, and 220 predicted sites for
      phosphorylation by protein kinases (casein kinase 2, protein kinase C, and
      proline-directed protein kinase). Secondary structure and folding of the inserted
      amino acid residues were deduced from properties of recombinant polypeptides.
      Frictional ratios of 1.9-2.4 were calculated from Stokes radii and sedimentation
      coefficients, for polypeptides comprising 70% of the inserted sequence,
      indicating a highly asymmetric shape. Circular dichroism spectra of these
      polypeptides indicate a nonglobular structure with negligible alpha-helix or beta
      sheet folding. These results suggest a ball-and-chain model for 440-kD ankyrinB
      with a membrane-associated globular head domain and an extended filamentous tail
      domain encoded by the inserted sequence. Immunofluorescence and immunoblot
      studies of developing neonatal rat optic nerve indicate that 440-kD ankyrinB is
      selectively targeted to premyelinated axons, and that 440-kD ankyrinB disappears
      from these axons coincident with myelination. Hypomyelinated nerve tracts of the
      myelin-deficient Shiverer mice exhibit elevated levels of 440-kD ankyrinB. 440-kD
      ankyrinB thus is a specific component of unmyelinated axons and expression of 440
      kD ankyrinB may be downregulated as a consequence of myelination.

PMID- 8253845
TI  - Interpolar spindle microtubules in PTK cells.
AB  - Spindle microtubules (MTs) in PtK1 cells, fixed at stages from metaphase to
      telophase, have been reconstructed using serial sections, electron microscopy,
      and computer image processing. We have studied the class of MTs that form an
      interdigitating system connecting the two spindle poles (interpolar MTs or ipMTs)
      and their relationship to the spindle MTs that attach to kinetochores (kMTs).
      Viewed in cross section, the ipMTs cluster with antiparallel near neighbors
      throughout mitosis; this bundling becomes much more pronounced as anaphase
      proceeds. While the minus ends of most kMTs are near the poles, those of the
      ipMTs are spread over half of the spindle length, with at least 50% lying > 1.5
      microns from the poles. Longitudinal views of the ipMT bundles demonstrate a
      major rearrangement of their plus ends between mid- and late anaphase B. However,
      the minus ends of these MTs do not move appreciably farther from the spindle
      midplane, suggesting that sliding of these MTs contributes little to anaphase B.
      The minus ends of ipMTs are markedly clustered in the bundles of kMTs throughout
      anaphase A. These ends lie close to kMTs much more frequently than would be
      expected by chance, suggesting a specific interaction. As sister kinetochores
      separate and kMTs shorten, the minus ends of the kMTs remain associated with the
      spindle poles, but the minus ends of many ipMTs are released from the kMT
      bundles, allowing the spindle pole and the kMTs to move away from the ipMTs as
      the spindle elongates.

PMID- 8253846
TI  - Regulated docking of nuclear membrane vesicles to vimentin filaments during
      mitosis.
AB  - During mitosis, several types of intermediate-sized filaments (IFs) undergo an
      extensive remodelling in response to phosphorylation by cdc 2 and other protein
      kinases. However, unlike the nuclear lamins, the cytoplasmic IFs do not seem to
      follow a fixed disassembly stereotype and often retain their physical continuity
      without depolymerizing into soluble subunits. To investigate potential
      interactions between mitotically modified IFs and other cellular structures, we
      have examined prometaphase-arrested cells expressing the IF protein vimentin. We
      demonstrate here that vimentin filaments associate in situ and co-fractionate
      with a distinct population of mitotic vesicles. These vesicles carry on their
      surfaces nuclear lamin B, the inner nuclear membrane protein p58, and wheat germ
      agglutinin (WGA)-binding proteins. Consistent with a tight interaction between
      the IFs and the mitotic membranes, vimentin, nuclear lamin B, and a 180-kD WGA
      binding protein are co-isolated when whole mitotic homogenates are incubated with
      anti-vimentin or anti-lamin B antibodies immobilized on magnetic beads. The
      vimentin-associated vesicles are essentially depleted of ER, Golgi and endosomal
      membrane proteins. The interaction of vimentin with lamin B-carrying membranes
      depends on phosphorylation and is weakened by dephosphorylation during nuclear
      reassembly in vitro. These observations reveal a novel interaction between IFs
      and cellular membranes and further suggest that the vimentin filaments may serve
      as a transient docking site for inner nuclear membrane vesicles during mitosis.

PMID- 8253847
TI  - The rod domain of NF-L determines neurofilament architecture, whereas the end
      domains specify filament assembly and network formation.
AB  - Neurofilaments, assembled from NF-L, NF-M, and NF-H subunits, are the most
      abundant structural elements in myelinated axons. Although all three subunits
      contain a central, alpha-helical rod domain thought to mediate filament assembly,
      only NF-L self-assembles into 10-nm filaments in vitro. To explore the roles of
      the central rod, the NH2-terminal head and the COOH-terminal tail domain in
      filament assembly, full-length, headless, tailless, and rod only fragments of
      mouse NF-L were expressed in bacteria, purified, and their structure and assembly
      properties examined by conventional and scanning transmission electron microscopy
      (TEM and STEM). These experiments revealed that in vitro assembly of NF-L into
      bona fide 10-nm filaments requires both end domains: whereas the NH2-terminal
      head domain promotes lateral association of protofilaments into protofibrils and
      ultimately 10-nm filaments, the COOH-terminal tail domain controls lateral
      assembly of protofilaments so that it terminates at the 10-nm filament level.
      Hence, the two end domains of NF-L have antagonistic effects on the lateral
      association of protofilaments into higher-order structures, with the effect of
      the COOH-terminal tail domain being dominant over that of the NH2-terminal head
      domain. Consideration of the 21-nm axial beading commonly observed with 10-nm
      filaments, the approximate 21-nm axial periodicity measured on paracrystals, and
      recent cross-linking data combine to support a molecular model for intermediate
      filament architecture in which the 44-46-nm long dimer rods overlap by 1-3-nm
      head-to-tail, whereas laterally they align antiparallel both unstaggered and
      approximately half-staggered.

PMID- 8253848
TI  - Neural regulation of muscle acetylcholine receptor epsilon- and alpha-subunit
      gene promoters in transgenic mice.
AB  - The effects of denervation were investigated in mice with transgenes containing
      promoter elements from the muscle acetylcholine receptor epsilon- and alpha
      subunit genes. The promoter sequences were coupled to a nuclear localization
      signal-beta-galactosidase fusion gene (nlacZ) as a reporter. While many
      postsynaptic specializations form in the embryo, expression of the epsilon
      subunit is induced during the first two postnatal weeks. When muscles were
      denervated at birth, before the onset of epsilon expression, epsilon nlacZ still
      appeared at the former synaptic sites on schedule. This result suggests that the
      nerve leaves a localized "trace" in the muscle that can continue to regulate
      transcription. An additional finding was that epsilon nlacZ expression was much
      stronger in denervated than in intact muscles. This suggests that the epsilon
      promoter is similar to the other subunits in containing elements that are
      activated on cessation of neural activity. However, even after denervation,
      epsilon nlacZ expression was always confined to the synaptic region whereas alpha
      nlacZ expression increased in nuclei along the entire length of the fiber. This
      suggests that while the epsilon gene is similar in its activity dependence to
      other subunit genes, it is unique in that local nerve-derived signals are
      essential for its expression. Consequently, inactivity enhances epsilon
      expression only in synaptic nuclei where such signals are present, but enhances
      expression throughout the muscle fiber. Truncations and an internal deletion of
      the epsilon promoter indicate that cis-elements essential for the response to
      synaptic signals are contained within 280 bp of the transcription start site. In
      contrast to these results in young animals, denervation in older animals leads to
      an unexpected reduction in nlacZ activity. However, mRNA measurements indicated
      that transgene expression was increased in these animals. This discordance
      between nlacZ mRNA and enzyme activity, demonstrates a previously unknown
      limitation of nlacZ as a reporter gene in transgenic animals.

PMID- 8253849
TI  - Targeted expression of a conditional oncogene in hematopoietic cells of
      transgenic mice.
AB  - We have produced two lines of transgenic mice in which the expression of
      temperature-sensitive SV-40 large T antigen is targeted to bone marrow
      megakaryocytes via the platelet factor 4 (PF4) tissue-specific promoter. The
      progeny of these transgenic mice were observed for about 3 mo, and no
      malignancies were detected over this period of time. The offspring of these
      transgenic mice, 6- to 12-wk of age, served as a source of bone marrow cells,
      which upon in vitro cultivation at the permissive temperature yielded
      immortalized cell lines (MegT). At the permissive temperature, MegT cells exhibit
      the characteristics of early 2N and 4N megakaryocytes which include the presence
      of specific gene products such as PF4, glycoprotein IIb, acetylcholinesterase,
      and CD45 as well as the absence of molecular markers of other cell lineages such
      as the macrophage marker Mac-1, the T helper cell marker CD4, the mast cell
      marker IgE, the T cell marker CD2 or the erythroid cell marker alpha-globin. The
      inactivation of the oncogene by a shift of temperature from 34 degrees to 39.5
      degrees C produces a reduction in the frequency of the 2N cells, in conjunction
      with the appearance of 8N and 16N cells, consisting of 27 and 3% of total cells,
      respectively. Thus, we have generated hematopoietic cell lines that are trapped
      in the early stages of megakaryocyte commitment, but able to undergo part of the
      normal program of terminal differentiation.

PMID- 8253850
TI  - Ectopic trkA expression mediates a NGF survival response in NGF-independent
      sensory neurons but not in parasympathetic neurons.
AB  - We have investigated the role of trkA, the tyrosine kinase NGF receptor, in
      mediating the survival response of embryonic neurons to NGF. Embryonic trigeminal
      mesencephalic (TMN) neurons, which normally survive in the presence of brain
      derived neurotrophic factor (BDNF) but not NGF, become NGF-responsive when
      microinjected with an expression vector containing trkA cDNA. In contrast,
      microinjection of ciliary neurotrophic factor (CNTF)-dependent embryonic ciliary
      neurons with the same construct does not result in the acquisition of NGF
      responsiveness by these neurons despite de novo expression of trkA mRNA and
      protein. The failure of trkA to result in an NGF-promoted survival response in
      ciliary neurons is not due to absence of the low-affinity NGF receptor, p75, in
      these neurons. Quantitative RT/PCR and immunocytochemistry showed that TMN and
      ciliary neurons both express p75 mRNA and protein. These findings not only
      provide the first direct experimental demonstration of trkA mediating a
      physiological response in an appropriate cell type, namely NGF-promoted survival
      of embryonic neurons, but indicate that not all neurons are able to respond to a
      trkA-mediated signal transduction event.

PMID- 8253851
TI  - IGF-I is a mitogen involved in differentiation-related gene expression in fetal
      rat brown adipocytes.
AB  - Fetal rat brown adipocytes at time zero of culture constitute a population of
      cells of broad spectrum, as estimated by cell size, endogenous fluorescence and
      lipid content, and show an intrinsic mitogenic competence. They express
      constitutively early growth-related genes such as c-myc, c-fos, and beta-actin,
      tissue specific-genes such as the uncoupling protein (UCP) and the lipogenic
      marker malic enzyme (ME). Fetal brown adipocytes bear a high expression of
      insulin-like growth factor receptor (IGF-IR), and show a high affinity IGF-I
      specific-binding to its receptor, and a high number of binding sites per cell.
      After cell quiescence, insulin-like growth factor I (IGF-I) was as potent as 10%
      FCS in inducing DNA synthesis, cell number increase, and the entry of cells into
      the cell-cycle. In addition, IGF-I or 10% FCS for 48 h increased the percentage
      of [3H]thymidine-labeled nuclei as compared to quiescent cells. Single cell
      autoradiographic microphotographs show typical multilocular fat droplets brown
      adipocytes, resulting positive to [3H]thymidine-labeled nuclei in response to IGF
      I. IGF-I increased mRNA expression of the early-response genes c-fos (30 min), c
      myc (2 and 24 h), and H-ras (4 and 24 h). 10% FCS also increased c-fos and c-myc,
      but failed to increase H-ras as an early event. IGF-I or 10% FCS, however,
      similarly increased the mRNA late expression of c-myc, H-ras, c-raf, beta-actin,
      and glucose 6-phosphate dehydrogenase (G6PD) at 72 h, as compared to quiescent
      cells. IGF-I or FCS maintained at 24 h or increased at 48 and 72 h UCP mRNA
      expression. The results demonstrate that IGF-I is a mitogen for fetal rat brown
      adipocytes, capable of inducing the expression of early and late growth-regulated
      genes, and of increasing the lipogenic marker ME and the tissue-specific gene
      UCP, suggesting the involvement of IGF-I in the differentiation as well as in the
      proliferation processes.

PMID- 8253852
TI  - Multiple levels of control of the stage- and region-specific expression of rat
      intestinal lactase.
AB  - To elucidate the mechanisms leading to the functional regionalization of the
      digestive epithelium, lactase expression was analyzed at the protein, mRNA and
      gene levels, along the intestinal tract at various stages of the rat postnatal
      development. In the colon of neonates, the transient expression of mRNA and
      enzyme correlated well with gene transcription. In contrast to the colon, complex
      patterns were observed in the small intestine. In suckling animals, the mRNA was
      present at a high level despite the progressive decline of enzyme activity.
      Crypts were devoid of mRNA and the transcript mainly accumulated in the lower
      half of the villi. From weaning onwards, a functional regionalization of the
      epithelium was defined, characterized by the modification of the longitudinal
      distribution of lactase mRNA. Indeed the transcript remained abundant in the
      distal duodenum, jejunum and proximal ileum, but decreased in the proximal
      duodenum and became virtually absent in the distal ileum. Concomitantly, the mRNA
      and enzyme distribution along the villi changed in the different segments of the
      small intestine. Patterns similar to those described in sucklings were retained
      in the adult jejunum. In contrast, mRNA and enzyme could no longer be detected in
      the distal ileum, while mosaicism appeared in the proximal duodenum. In vitro
      transcription assays carried out with isolated nuclei suggested that the decay of
      lactase mRNA in the proximal duodenum at weaning was associated with a decreasing
      rate of transcription of the gene. However active gene transcription was retained
      in the nuclei of the adult jejunum and ileum. The loss of mRNA in the adult
      distal ileum despite the maintenance of active transcription did not result from
      an intragenic block of pre-RNA elongation, as shown by transcription assays
      carried out at various positions of the lactase gene. In addition, we looked for
      the ontogenic decline of lactase protein despite the maintenance of a high amount
      of mRNA in the jejunum, and it became evident that the fraction of mRNA present
      in polysomes was constant with age. Taken together, these data indicate that
      lactase constitutes an unusual marker of development and of functional
      regionalization of the intestinal tract which exhibits a complex time- and space
      specific pattern of gene, mRNA, and protein expression. The distinct patterns
      occurring in the duodenum, jejunum, ileum, and the colon of pre- and postweaned
      rats depend on a combination of transcriptional, posttranscriptional, and
      posttranslational levels of regulation. and are associated with a different mRNA
      distribution along villi in each intestinal segment.

PMID- 8253853
TI  - Differential effects of over-expressed neural cell adhesion molecule isoforms on
      myoblast fusion.
AB  - We have used a transfection based approach to analyze the role of neural cell
      adhesion molecule (NCAM) in myogenesis at the stage of myoblast fusion to form
      multinucleate myotubes. Stable cell lines of myogenic C2 cells were isolated that
      express the transmembrane 140- or 180-kD NCAM isoforms or the
      glycosylphosphatidylinositol (GPI) linked isoforms of 120 or 125 kD. We found
      that expression of the 140-kD transmembrane isoform led to a potent enhancement
      of myoblast fusion. The 125-kD GPI-linked NCAM also enhanced the rate of fusion
      but less so when a direct comparison of cell surface levels of the 140-kD
      transmembrane form was carried out. While the 180-kD transmembrane NCAM isoform
      was effective in promoting C2 cell fusion similar to the 140-kD isoform, the 120
      kD isoform did not have an effect on fusion parameters. It is possible that these
      alterations in cell fusion are associated with cis NCAM interactions in the plane
      of the membrane. While all of the transfected human NCAMs (the transmembrane 140-
      and 180-kD isoforms and the 125- and 120-kD GPI isoforms) could be clustered in
      the plane of the plasma membrane by species-specific antibodies there was a
      concomitant clustering of the endogenous mouse NCAM protein in all cases except
      with the 120-kD human isoform. These studies show that different isoforms of NCAM
      can undergo specific interactions in the plasma membrane which are likely to be
      important in fusion. While the transmembrane and the 125-kD GPI-anchored NCAMs
      are capable of enhancing fusion the 120-kD GPI NCAM is not. Thus it is likely
      that interactions associated with NCAM intracellular domains and also the muscle
      specific domain (MSD) region in the extracellular domain of the GPI-linked 125-kD
      NCAM are important. In particular this is the first role ascribed to the O-linked
      carbohydrate containing MSD region which is specifically expressed in skeletal
      muscle.

PMID- 8253854
TI  - In vitro expression of osteoblastic markers in cells isolated from normal fetal
      and postnatal human bone and from bone of patients with osteogenesis imperfecta.
AB  - We studied the expression of osteoblastic markers in cultured cells isolated from
      the bone of 15 patients with different clinical forms of osteogenesis imperfecta
      (OI) and of seven fetal and postnatal controls. Cultured bone cells of ten OI
      patients produced abnormal collagen type I. Similar to controls, OI bone cells
      produced predominantly collagen type I with traces of collagen types III and V.
      The 1,25(OH)2 vitamin D3-stimulated synthesis of osteocalcin, a specific
      osteoblastic marker protein, was similar in OI bone cells and age-matched
      controls. Bone cells from fetal controls and from patients with the perinatal
      lethal OI type II produced less osteocalcin than bone cells from postnatal
      controls and surviving OI patients. OI bone cells responded to parathyroid
      hormone (PTH) by increased production of cAMP similar to controls. Bone cells
      from fetal controls and from OI type II donors showed a decreased response to
      PTH. Activity of the bone-liver-kidney isoenzyme alkaline phosphatase (AP) was
      detected in all control and OI bone cells. The expression of all osteoblastic
      markers was similar in bone cells producing abnormal collagen type I. These
      observations show that OI bone cells in vitro express a pattern of osteoblastic
      markers similar to age-matched control bone cells indicating that osteoblastic
      differentiation is not altered by the underlying defects of collagen type I
      metabolism in OI bone cells.

PMID- 8253855
TI  - Inhibitors of vacuolar-type H(+)-ATPase suppresses proliferation of cultured
      cells.
AB  - We investigated effects of bafilomycin A1, a specific inhibitor of vacuolar-type
      H(+)-ATPase (V-ATPase), and its analogues on proliferation of various cultured
      cells. The proliferation of the various cell lines was suppressed by adding
      bafilomycin A1 to the culture medium. This inhibitory effect appeared at a
      concentration of nanomolar order and was dose dependent. Although the suppression
      was reversible, the drug exerted not only suppression of the proliferation but
      also death to some cell lines. Drug concentration required for 50% inhibition of
      the cell proliferation during 48 h differed markedly depending on cell species
      and the sensitivity appears to increase by the transformation of the cells. Two
      derivatives of concanamycin A, an analogue of bafilomycin A1, also inhibited
      strongly V-ATPase in vitro and in vivo, and simultaneously cell proliferation.
      Two concanamycin A derivatives which have lost inhibitory effect on V-ATPase lost
      inhibitory effect on cell proliferation as well. These results suggest that V
      ATPase is involved in the machinery maintaining the cell proliferation.

PMID- 8253856
TI  - Relative roles of Na+/H+ exchange and vacuolar-type H+ ATPases in regulating
      cytoplasmic pH and function in murine peritoneal macrophages.
AB  - Two distinct mechanisms have been shown to mediate cytoplasmic pH (pHi) recovery
      in acid-loaded peritoneal macrophages (M phi s): Na+/H+ exchange and H+ extrusion
      by vacuolar-type (V-type) H+ ATPases. The present studies examined the relative
      roles of these two systems in maintaining pHi and cell function. Measurements of
      M phi pHi and superoxide (O2-) production in response to stimulation with 12-O
      tetradecanoyl phorbol 13-acetate (TPA) were made at physiological or acidic
      extracellular pH (pHo) levels. The V-type H+ ATPase inhibitor, bafilomycin A1,
      and the potent Na+/H+ exchange inhibitor, N-ethyl-N-propylamino amiloride (EPA),
      were used to examine the contributions of these ion transporters to pHi
      regulation and cell function. At pHo 7.35, the complementary activities of the
      Na+/H+ antiport and the V-type H+ ATPase mediate pHi homeostasis. At pHo 6.7,
      maintenance of pHi depends primarily on H+ ATPase activity: bafilomycin A1
      reduced pHi from 6.8 +/- 0.02 in control cells to 6.59 +/- 0.01 (P < 0.01) while
      EPA was without effect. The functional importance of V-type H+ ATPase-activity in
      preserving pHi homeostasis at acidic extracellular pH levels was reflected by the
      impairment of O2- production at pHo 6.70 when H+ ATPase activity was inhibited:
      bafilomycin A1 reduced O2- production from 13.9 +/- 1.0 to 9.3 +/- 0.6
      nmoles/10(6) cells/40 min, in control and bafilomycin A1-treated cells,
      respectively (P < 0.05), while EPA had no effect. In subsequent studies, pHi was
      independently manipulated using the ionophore nigericin. Lowering pHi from 6.80
      to 6.60 reduced O2- production from 15.3 +/- 1.8 to 9.8 +/- 1.6 nmoles/10(6)
      cells/40 min (P < 0.05), indicating that the cytoplasmic acidification resulting
      from inhibition of H+ ATPases at low pHo could account for the associated
      impairment of O2- production. In a more profoundly acidic environment (pHo 6.35),
      H+ ATPases remained active in regulating pHi, but could not preserve a
      sufficiently physiological pHi to support respiratory burst activity. V-type H+
      ATPases constitute the dominant mechanism by which the pHi of peritoneal M phi s
      is maintained in an acidic extracellular environment.

PMID- 8253857
TI  - Effects of mitogens and co-mitogens on the formation of small-cell colonies in
      primary cultures of rat hepatocytes.
AB  - Colonies of small hepatocytes appeared after the culture of primary adult rat
      hepatocytes for 4 days in serum-free Dulbecco's modified Eagle's medium
      containing 10 mM nicotinamide and 10 ng/ml of epidermal growth factor (EGF),
      acidic and basic fibroblast growth factors (FGF), hepatocyte growth factor (HGF),
      or transforming growth factor-alpha (TGF-alpha). Every colony consisted of cells
      that each had a single nucleus and a higher nucleus/cytoplasm ratio than
      surrounding hepatocytes, and immunocytochemically the cells induced by any
      mitogen were stained with albumin, transferrin, cytokeratin-8 and -18. But these
      cells expressed neither cytokeratin-7 nor -19. When 6 x 10(5) cells were plated
      on 35-mm dishes, about 15 colonies per 1,000 attached cells were observed in the
      cultures treated with EGF, HGF, and TGF-alpha. Although FGFs could also induce
      colonies, their number was less than half of the number induced by EGF.
      Furthermore, the numbers of colonies induced by the combinations of EGF+HGF,
      EGF+TGF-alpha, and HGF+TGF-alpha were not different from those of the colonies
      induced by each mitogen alone. To examine the ability of co-mitogenic factors to
      induce small-cell colonies, angiotensin-II, insulin-like growth factor-I,
      norepinephrine, tumor necrosis factor, and vasopressin were used. In the cells
      cultured without EGF, these co-mitogens neither stimulated DNA synthesis nor
      induced colonies. On the other hand, in cells cultured with both EGF and each co
      mitogen, although the DNA synthesis of the hepatocytes was enhanced, the number
      of colonies detected was not significantly different from the number which EGF
      alone could induce. These results showed that the small-cell colonies in primary
      cultures of rat hepatocytes were inducible by EGF, HGF, TGF-alpha, or FGFs and
      that the co-mitogens did not influence the formation of the small-cell colonies.

PMID- 8253858
TI  - Lipid synthesis and secretion by primary cultures of rat mammary epithelial
      cells.
AB  - Lipid synthesis and secretion was measured in primary rat mammary epithelial
      cells cultured on basement matrix in medium supplemented with lactogenic
      hormones. The cells grew and differentiated to form alveolar-like structures
      reminiscent of lactating mammary gland. They synthesized abundant
      triacylglycerol, containing fatty acids characteristic of rat milk (C10:0-C14:0),
      using 14C-glucose, 14C-oleic acid or 14C-glycerol as precursors. Basal levels of
      triacylglycerol secretion were measured using 14C-oleic acid labeling; 1.3 +/-
      0.3% of the labeled cellular triacylglycerol was secreted into the medium in 24
      hours. Secreted lipid droplets were surrounded by a bilayer membrane with an
      electron-dense inner coat characteristic of fat globules secreted by the mammary
      gland. The rate of triglycerol secretion was increased to 998 +/- 98% of control
      (P < 0.01) by the addition of phorbol 12-myristate 13-acetate (PMA) in
      combination with staurosporine, a protein kinase inhibitor. Several other protein
      kinase inhibitors, when combined with PMA, also markedly stimulated secretion.
      Effective protein kinase inhibitors included sphingosine (has diverse cellular
      effects including the inhibition of protein kinase C; 13-fold increase in
      secretion), and KT5823 (a cGMP dependent protein kinase inhibitor; 5-fold
      increase). KT5720 (a cAMP-dependent protein kinase inhibitor) did not alter
      secretion. Kinase inhibitors were effective only in the presence of a phorbol
      ester. 4 alpha-phorbol-12,13-didecanoate, a phorbol ester which does not activate
      protein kinase C (PKC), could substitute for PMA. Lipid release was not mediated
      by disruption of cell-cell tight junctions, as EGTA did not release lipid. Based
      on these observations we suggest that two signals are needed to enable or
      stimulate lipid secretion in cultured rat mammary epithelial cells: 1) inhibition
      of a protein kinase and 2) a PKC-independent effect of phorbol ester. We have,
      for the first time, characterized a cell culture model suitable for studying
      lipid synthesis and secretion by mammary epithelial cells.

PMID- 8253859
TI  - Novel marine alkaloids from the tunicate Eudistoma sp. are potent regulators of
      cellular growth and differentiation and affect cAMP-mediated processes.
AB  - Six novel alkaloids that contain a fused tetracyclic pyrido[2,3,4-kl]acridine
      ring system were purified recently from the Red Sea purple tunicate Eudistoma sp.
      Evaluation of the effects of these alkaloids on cultured neuroblastoma and
      fibroblast cells revealed that they possess potent growth regulatory properties,
      and affect cell shape and adhesion. In mouse neuroblastoma cells, the Eudistoma
      alkaloids inhibited cell proliferation and induced a process of differentiation
      during which the cells flattened onto the surface, increased considerably in
      size, and extended long neurites. In hamster fibroblasts the alkaloids slowed
      down cell multiplication, and caused an exceptional cell flattening or
      elongation. In a virus-transformed derivative of the hamster fibroblasts the
      alkaloids restored many aspects of normal cell growth and morphology. In
      addition, several of the alkaloids mimicked the effects of cAMP analogs on two
      well-characterized cAMP-mediated processes involved in hepatic glucose metabolism
      -inhibition of pyruvate kinase (PK) activity and induction of mRNA for
      phosphoenolpyruvate carboxykinase (PEPCK). All these effects suggest that the
      Eudistoma alkaloids may act on the cAMP signaling system. However, a single
      application of these compounds was sufficient to completely block cell
      multiplication and to induce and sustain differentiation and "reverse
      transformation". Furthermore, these effects were not readily reversible following
      removal of the drugs. In contrast, a single application of agents that mimic or
      elevate cAMP induced a transient response that waned with time in culture, and
      the effects induced by constant elevation of cAMP reverse rapidly following drug
      removal. We propose that the Eudistoma alkaloids cause growth inhibition,
      differentiation, and reverse transformation by modifying the activity state of
      proteins that are involved in the regulation of cell shape and adhesion and serve
      as a target for the cAMP and/or other second messenger systems.

PMID- 8253860
TI  - Polyamine transport regulation by calcium and calmodulin: role of Ca(2+)-ATPase.
AB  - The study was conducted on human leukemia (K 562) cells to characterize the
      mechanisms implicated in the regulation of the polyamine spermidine (Spd)
      transport process. The antagonists of calmodulin, trifluoperazine (TFP), W-7 (N
      [6-aminohexyl]-5-chloro-1-naphthelenesulfonamide), or mellitin inhibited
      significantly polyamine Spd uptake in these cells. The translocation of
      calmodulin towards plasma membrane and a concomitant decrease in its contents in
      cytosol were directly correlated with the time course increases similar to that
      of Spd uptake, indicating that calmodulin is recruited towards plasma membrane
      during the Spd transport process. Diminution of free intracellular calcium,
      (Ca2+)i, by preincubating the cells in BAPTA (bis[2-amino-5-methylphenoxyl]
      ethane-N,N,N',N',-tetraacetate) buffer inhibited Spd transport significantly.
      Addition of lanthanum (LAN), a molecule known to inhibit Ca2+ efflux via Ca(2+)
      ATPase, curtailed Spd uptake by these cells. LAN inhibited Vmax, but not the Km,
      of Spd uptake, indicating that the former does not directly interact with the
      polyamine transporter; rather it regulates the transport process, probably via
      its action on Ca(2+)-ATPase. Calmodulin-stimulated uptake of 45Ca2+ by inside-out
      vesicles of K 562 cells, a measure of Ca(2+)-ATPase activity. Furthermore,
      addition of LAN inhibited both basal and calmodulin-stimulated activity of Ca(2+)
      ATPase. Thapsigargin (THAP), a molecule known to elevate (Ca2+)i due to its
      action on the endoplasmic reticulum, increased Spd transport whereas addition of
      LAN inhibited THAP-stimulated Spd transport activity. THAP increased free (Ca2+)i
      in these cells, and a pre-addition of LAN to these cells curtailed the THAP
      stimulated increases of (Ca2+)i concentrations. Addition of Spd brought about
      elevations in (Ca2+)i contents. Caffeine also increased (Ca2+)i in these cells;
      however, it failed to stimulate significantly the Spd uptake process, indicating
      that (Ca2+)i which is involved in the regulation of polyamine transport pathways
      does not belong to the calcium-induced calcium-release (CICR) pool. Replacement
      of Ca2+ from the incubation medium (i.e., 0% Ca2+) resulted in higher uptake
      activity as compared to that in 100% Ca2+ medium, demonstrating that in 100% Ca2+
      medium the calcium efflux process is quickly compensated by calcium
      refilling/influx from the extracellular medium, while in 0% Ca2+ medium there is
      perpetual efflux of (Ca2+)i which contributes to higher Spd uptake process. The
      results of this study suggest that an increase in free (Ca2+)i and its release
      from the cells via Ca(2+)-ATPase, and concomitant activation of calmodulin, which
      controls Ca(2+)-pump activity, are involved in the regulation of the Spd uptake
      process in human leukemia cells.

PMID- 8253861
TI  - Growth inhibition of breast cancer cells induced by exogenous ATP.
AB  - Addition of ATP (> 0.1 mM) to cultures of human breast cancer T47D cells resulted
      in an inhibition of cell proliferation. The inhibition was found to be specific
      for ATP, and dependent on its concentration. Growth inhibition continued for at
      least three days, although ATP and its hydrolysis products were metabolized
      within one day. Conditioned medium from ATP-treated cultures (CM+) was found to
      inhibit the growth of cells that were not exposed to ATP. This is an indication
      that extracellular factors, besides ATP, are involved in the inhibition process.
      The inhibition was maintained after dialysis of the CM+, using an 8 kDa cut-off
      membrane. Conditioned medium from untreated cultures (CM-), however, only
      slightly affected cell growth. The data suggest that the CM(+)-induced cell
      growth inhibition is mediated by an ATP-activated growth inhibiting factor. Flow
      microfluorometry and thymidine incorporation experiments have shown that the
      growth arrest is mainly due to the elongation of the S-phase of the cell cycle.

PMID- 8253862
TI  - Coupling of glucose transport and phosphorylation in Xenopus oocytes and cultured
      cells: determination of the rate-limiting step.
AB  - The initial events in glucose metabolism by all cells are the transport and
      phosphorylation of glucose. To quantify the relative contributions of these two
      processes to overall glucose utilization, we have developed an experimental
      approach for their in situ measurement as parallel processes. The method is based
      on the use of intracellular [2-3H]glucose as a substrate for both the transporter
      and hexokinase, and involves simultaneous measurement of [2-3H]glucose efflux and
      of 3H2O released by phosphorylation. The Xenopus oocyte expression system was
      used to test the method, since in these cells transport and phosphorylation
      activities can be regulated by expression of mRNA or injection of foreign
      protein. Oocytes microinjected with [2-3H]glucose showed no release of injected
      glucose, but did have saturable phosphorylation kinetics, with a Km of 40 microM
      and a Vmax of 0.1 nmol/min/oocyte. Co-injection of yeast hexokinase increased
      glucose phosphorylation by five-fold. Expression of human glucose transporter
      (GLUT1) mRNA resulted in a 25-30-fold increase in the rate of saturable efflux of
      microinjected glucose compared to control oocytes. The kinetics of transport and
      phosphorylation of [2-3H]glucose were analyzed by a multiple curve-fitting
      program that provided estimates of kinetic coefficients for both processes from a
      single time course. The analysis showed that expression of GLUT1 shifted the rate
      limiting step in glucose utilization from transport to phosphorylation. A similar
      shift occurred at a three-fold lower extracellular concentration of 2
      deoxyglucose. In a pancreatic beta cell line both transport and phosphorylation
      showed high Km values, with phosphorylation as the limiting step. The in situ
      measurement of glucose transport and phosphorylation as parallel processes should
      be useful in defining the relative contributions of each step to overall glucose
      metabolism in other cell and tissue models.

PMID- 8253863
TI  - Long-term effects of tumor necrosis factor on LLC-PK1 transepithelial resistance.
AB  - Renal epithelial LLC-PK1 cell sheets incubated with tumor necrosis factor (TNF)
      undergo an acute, spontaneous, and rapidly reversible decrease in transepithelial
      resistance (TER). (Mullin et al., 1992). However, 24 to 72 h following TNF
      exposure, TER across the cell sheet increases 2-fold. This later effect of TNF is
      also reversible, albeit slowly. The TER of TNF-treated cell sheets then declines
      toward initial levels between 72 and 144 h following exposure to the cytokine.
      Whereas the long-term increase in TER following TNF exposure is not associated
      with a decreased transepithelial 14C-mannitol flux (size selectivity), the charge
      (anionic) selectivity of the LLC-PK1 tight junction is decreased. Basal-lateral
      (ouabain and bumetanide-insensitive) Rb+ and apical Na+-dependent alpha
      methylglucoside (AMG) uptake into the cell are both reduced in cultures exposed
      to TNF 24 h earlier. Correspondingly, this long-term effect on TER is accompanied
      by a 30% decrease in short circuit current (iscc). Along with an observed
      increase in basal-lateral methylamino-isobutyric acid (MeAIB) influx into the
      cells, an increased incorporation of [3H]-thymidine into DNA indicates increased
      cell cycling after exposure to TNF. While the increase in cell cycling is not
      sustained for the duration of the elevation in TER, it does appear to initiate a
      sequence of events that lead to the sustained increase in TER. A decrease in the
      lateral intercellular space, observed between these epithelial cells after long
      term TNF exposure, may be a mechanism for the elevated TER following from the
      mitogenesis and/or transport changes. This overall long-term tightening of an
      epithelium in response to TNF may function, in part, as a compensatory action of
      the epithelium to reestablish its effectiveness as a physiological barrier,
      following the acute effect of TNF.

PMID- 8253864
TI  - Plasminogen-dependent activation of latent transforming growth factor beta (TGF
      beta) by growing cultures of osteoblast-like cells.
AB  - Osteoblasts secrete transforming growth factor beta (TGF beta) as a biologically
      inert, latent complex that must be dissociated before the growth factor can exert
      its effects. We have examined the production and proteolytic activation of latent
      TGF beta (LTGF beta) by clonal UMR 106-01 rat osteosarcoma cells and neonatal
      mouse calvarial (MC) osteoblast-like cells in vitro. Synthetic bPTH-(1-34)
      increased the activity of tissue-type (tPA) and urokinase-type (uPA) plasminogen
      activators (PA) in cell lysates (CL) of UMR 106-01 cells. The concentration of
      active TGF beta in serum-free CM from cultures treated with bPTH-(1-34) and
      plasminogen was significantly greater than in CM from untreated controls and
      cultures treated with either bPTH-(1-34) or plasminogen alone. This effect
      occurred at concentrations of PTH-(1-34) that increased PA activity and was
      prevented by aprotinin, an inhibitor of plasmin activity. Treatment with bPTH-(1
      34) had no effect on the concentration of TGF beta in acid-activated samples of
      CM. Functional consequences of proteolytically activated TGF beta was examined in
      primary cultures of neonatal MC osteoblast-like cells. Human platelet TGF beta 1
      caused a dose-dependent increase in the migration of these cells in an in vitro
      wound healing assay. Cell migration was also stimulated in cultures treated with
      bPTH-(1-34) and plasminogen together. This effect was blocked by an anti-TGF beta
      1 antibody. The results of these studies demonstrate that (1) LTGF beta secreted
      by osteoblasts in vitro is activated under conditions where the plasmin activity
      in the cultures is increased, and (2) the TGF beta generated by plasmin-mediated
      proteolysis is biologically active. We suggest that the local concentration of
      TGF beta in bone may be controlled by the osteoblast-associated plasminogen
      activator/plasmin system. Furthermore, since several calciotropic factors
      influence osteoblast PA activity, this system may have an important role in
      mediating their anabolic and/or catabolic effects.

PMID- 8253865
TI  - Adenovirus and protein kinase C have distinct molecular requirements for
      regulating epidermal growth factor receptor trafficking.
AB  - The ligand-activated tyrosine kinase receptor for epidermal growth factor (EGF)
      is down-regulated by an integral membrane protein coded for by the E3 early
      transcription unit of group C adenoviruses. The E3 protein appears to block
      recycling of constitutively internalized receptors, causing them instead to
      traffic to lysosomes where they are degraded. Expression of functional EGF
      receptors is also regulated by protein kinase C (PKC), which directly
      phosphorylates the EGF receptor at Thr-654. The goal of this study was to
      determine potential interactions between PKC and the E3 protein, since membrane
      bound PKC activity is elevated by the adenovirus E1A protein. Our results show
      that although tumor promoters which activate PKC cause a coordinate induction of
      E3 protein synthesis and EGF receptor degradation, the E3 protein-induced pathway
      for receptor down-regulation functions independently of PKC and other kinases
      that are inhibited by staurosporine. This suggests that in contrast to other
      mechanisms that modulate receptor expression (i.e., ligand and PKC), the E3
      protein is not regulated by phosphorylation but is constitutively active. We also
      report that adenovirus-mediated degradation is the preferred pathway in infected
      cells stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce
      receptor recycling.

PMID- 8253866
TI  - Endothelial cell hypoxia associated proteins are cell and stress specific.
AB  - Vascular endothelial cells (EC) are one of the initial cells exposed to decreases
      in blood oxygen tension. Bovine EC respond not only by altering secretion of
      vasoactive, mitogenic, and thrombogenic substances, but also by developing
      adaptive mechanisms in order to survive acute and chronic hypoxic exposures. EC
      exposed to hypoxia in vitro upregulate a unique set of stress proteins of Mr 34,
      36, 39, 47, and 56 kD. Previous studies have shown that these proteins are cell
      associated, upregulated in a time and oxygen-concentration dependent manner, and
      are distinct from heat shock (HSPs) and glucose-regulated proteins (GRPs). To
      further characterize these hypoxia-associated proteins (HAPs), we investigated
      their upregulation in human EC from various vascular beds and compared this to
      possible HAP upregulation in other cell types. Human aortic, pulmonary artery,
      and microvascular EC upregulated the same set of proteins in response to hypoxia.
      In comparison, neither lung fibroblasts, pulmonary artery smooth muscle cells,
      pulmonary alveolar type II cells, nor renal tubular epithelial cells upregulated
      proteins of these Mr. Instead, most of these cell types induced synthesis of
      proteins of Mrs corresponding to either HSPs, GRPs, or both. Further studies
      demonstrated that exposure of EC to related stresses such as cyanide, 2
      deoxyglucose, hydrogen peroxide, dithiothreitol, and glucose deprivation did not
      cause upregulation of HAPs. Evaluation of cellular damage during hypoxia using
      phase-contrast microscopy, trypan blue exclusion, chromium release, and adherent
      cell counts showed that EC survived longer with less damage than any of the above
      cell types. The induction of HAPs, and the lack of induction of HSPs or GRPs, by
      EC in response to hypoxia may be related to their unique ability to tolerate
      hypoxia for prolonged periods.

PMID- 8253867
TI  - Superoxide-mediated lysis of erythrocytes: the role of colloid-osmotic forces.
AB  - Although superoxide anions are a well-known mediator of cytotoxicity, their
      mechanism of target cell lysis is not clearly understood. In the present study we
      have used an exogenous source of superoxide to study erythrocyte cytolysis. RBC
      lysis was studied in buffers containing the cations Li+, Na+, K+, Rb+, and Cs+;
      superoxide anions were produced and available in these buffers. During this model
      superoxide-dependent cytolytic process, erythrocytes underwent a shape change
      from biconcave disk to sphere as shown by scanning electron microscopy. Soret
      band transmitted light microscopy has confirmed this shape change and shown that
      it precedes cytosolic oxidation. This evidence is consistent with a colloid
      osmotic type lytic mechanism. Erythrocyte lysis was studied by 51Cr-release and
      light scattering methods. Superoxide-mediated target cytolysis was characterized
      by: 1) a sigmoidal dose-response curve and 2) a lag time in cytolysis after
      superoxide addition in kinetic light scattering experiments. The efficacy of
      cytolysis followed the rank order Cs+ > Rb+ > Na+, Li+ > sucrose = raffinose,
      which provides additional support for a colloid-osmotic lytic mechanism.
      Furthermore, the rank order potency correlates with the cations' hydration
      numbers. We suggest that oxidative events trigger the formation of colloid
      osmotic pores approximately 1 nm in diameter.

PMID- 8253868
TI  - Expression of a squamous cell marker, the spr1 gene, is posttranscriptionally
      down-regulated by retinol in airway epithelium.
AB  - Vitamin A (retinol) is required for the normal mucociliary differentiation of
      respiratory epithelium. A depletion of vitamin A promotes squamous cell
      metaplasia. To understand how vitamin A suppresses squamous cell differentiation,
      the expression of a squamous cell differentiation marker, the small proline-rich
      protein gene (spr1), was studied in cultured monkey tracheobronchial epithelial
      (TBE) cells. The expression of the spr1 gene was inhibited about 40 fold by
      retinol. The mRNA levels of the spr1 gene started to decline within 6 h of
      retinol treatment and reached a minimum level after 7 days. The inhibition by
      retinol was concentration dependent and did not require concurrent protein
      synthesis. The inhibition of the spr1 mRNA by retinol was not due to a decrease
      in the transcription rate of its gene but due to a decrease in its stability, as
      determined by nuclear run-on assays and mRNA half-life measurement, respectively.
      This result was further supported by a DNA transfection study using a chimeric
      construct containing the spr1 promoter region and the chloramphenicol
      acetyltransferase (CAT) reporter gene. The CAT activity in transfected cells was
      not inhibited by retinol. These results suggest that spr1 gene expression is
      posttranscriptionally down-regulated by retinol.

PMID- 8253869
TI  - Oxygen tension regulates neutrophil adhesion to human endothelial cells via an
      LFA-1-dependent mechanism.
AB  - Extravasation of leukocytes at the sites of ischemia-reperfusion is thought to
      exacerbate the tissue injury. It has been proposed that leukocyte accumulation is
      a secondary effect of the ischemic damage, mediated by inflammatory cytokines. We
      have recently demonstrated that physiologically low levels of oxygen tension
      alone can have a direct effect on the adhesive characteristics of mesenchymal
      cells for lymphocytes. We now report that decrease of oxygen tension in the
      environment induces the adhesion of neutrophils to human endothelial cells in
      culture. Adhesion of human neutrophils to human umbilical vein, bovine aortic,
      and mouse microvascular endothelial cell monolayers, which had been incubated at
      pO2 of 50 torr for 3 hours, increased 2.5-fold, 2-, and 1.5-fold, respectively.
      The effects of decreased oxygen concentration on adhesion were not mediated by a
      soluble factor elaborated by the hypoxic cells. Low oxygen tension upregulates a
      saturable, endothelial cell-associated adhesion mechanism, capable of
      withstanding centrifugation forces greater than 160g. Hypoxia-induced adhesion
      was inhibited by LFA-1-specific (CD11a/CD18 integrin) antibodies, but not by
      antibodies directed against the ICAM-1 ligand for the LFA-1 receptor. These
      studies demonstrate that decreases in oxygen tension alone increase the adhesive
      properties of endothelial cells for leukocytes. In addition, they provide
      evidence for the existence of a new ligand for the LFA-1 molecule on endothelial
      cells which can be affected by hypoxic environments.

PMID- 8253870
TI  - Activation of the 92 kDa type IV collagenase by tissue kallikrein.
AB  - Type IV collagenases are secreted as latent 92 and 72 kDa proenzymes which are
      then activated extracellularly. The mechanisms by which they are activated in
      vivo are not clear. We have studied the activation of porcine endothelial cell
      type IV collagenases by tissue and plasma kallikrein, and found that tissue
      kallikrein was a very efficient activator of the 92 kDa type IV collagenase.
      Enzyme cleavage was observed at concentrations of tissue kallikrein as low as 0.1
      microgram/ml. Plasma kallikrein had no effect. By comparison, plasmin, which has
      been proposed to be the physiological activator of interstitial collagenase and
      stromelysin, and elastase were much less effective, and high concentrations
      (plasmin at 100-200 micrograms/ml and elastase at 20 micrograms/ml) were required
      to cause only a limited cleavage which was not associated with an increase in
      activity, as observed by the gelatin-gel lysis assay. In addition tissue
      kallikrein was found by immunohistochemistry to be present in the extracellular
      matrix of the intima of porcine aortic vessel wall. These findings suggest that
      tissue kallikrein can be a potential activator of the 92 kDa type IV collagenase
      in vivo.

PMID- 8253871
TI  - Lipophilic impurity of phenol red is a potent cation transport modulator.
AB  - Previously, we described substantial alterations in the Na+ and K+ homeostasis of
      human skin fibroblasts following removal of fetal bovine serum (FBS). Herein, we
      report that FBS removal per se does not cause any cellular ionic changes unless a
      lipophilic impurity of commercial phenol red preparations is present. This
      substance accelerates 86Rb+ efflux four to seven times, causes a four to eight
      time increase in cellular Na+, and a 40-70% reduction in cellular K+ contents.
      FBS (10%) or albumin (0.8%) appears to bind the impurity thus inhibiting its
      action. The increased cellular Na+ and decreased K+ contents do not return to
      baseline within 4 hours following the removal of the phenol red extract. However,
      albumin completely reverses the cellular cationic changes that develop during a 2
      hour exposure of the cells to the free substance. The reversibility of its action
      by albumin suggests that the substance exerts its effect on or within the cell
      membrane and not intracellularly. Among seven different cell lines tested the
      86Rb+ efflux from, and the Na(+)-K+ contents of, COS-7 and Hs68 cells also
      responded to unpurified phenol red in a way similar to human fibroblasts. The
      amount of the phenol red contaminant is manufacturer dependent. As little as 0.5
      microM phenol red, from one vendor, was sufficient to elicit response in the
      86Rb+ efflux. Given that the impurity is unlikely to be more than a small
      fraction of phenol red, it seems to be a potent ionic transport modulator. Based
      on these results, the presence of commercial phenol red in serum-free growth or
      test media, including the increasing variety of chemically defined culture media,
      should be considered as a potential confounding factor in measurements that
      depend on intracellular Na(+)-K+ homeostasis. The findings of such earlier
      studies may need to be reconsidered if the cells were exposed to unbound phenol
      red. We recommend that, until the manufacturers further refine their product,
      phenol red be purified by ether extraction before its use. The evaluation of the
      potential physiologic or pharmacologic relevance of this potent cation transport
      modulator awaits its isolation.

PMID- 8253872
TI  - Morphological and proliferative responses of endothelial cells to hydrostatic
      pressure: role of fibroblast growth factor.
AB  - Subconfluent bovine pulmonary artery endothelial cells on rigid substrates were
      exposed to 1.5-15 cm H2O sustained hydrostatic pressure for up to 7 days and
      exhibited elongation, cytoskeletal rearrangement, increased cell proliferation,
      and bilayering. The role of basic fibroblast growth factor (bFGF) in the
      mechanism(s) of these endothelial cell responses to sustained hydrostatic
      pressure was investigated. Evidence that bFGF was released from endothelial cells
      exposed to sustained hydrostatic pressure or compression was provided by the
      following experimental results: 1) Cells exposed to control (3 mm H2O) pressure
      displayed intense nuclear and cytoplasmic bFGF staining by immunocytochemical
      techniques; this staining was absent in cells exposed to 10 cm H2O for 7 days. 2)
      Conditioned medium from endothelial cells exposed to 10 cm H2O for 7 days
      contained a transferable, growth-promoting activity exhibiting heparin-Sepharose
      affinity, lability to both heat and freeze/thawing, and neutralization by anti
      bovine bFGF. 3) Suramin (0.1 mM), a growth-factor receptor inhibitor, abrogated
      the proliferative and morphological responses of endothelial cells exposed to
      sustained hydrostatic pressure. Endothelial cells exposed to elevated hydrostatic
      pressure demonstrated no detectable decrement in cell viability as assessed by
      Trypan blue exclusion. The results of the present study indicate that hydrostatic
      pressure or compression can induce bFGF release from endothelial cells
      independent of cell injury or death; bFGF is subsequently responsible for the
      morphological, proliferative, and bilayering responses of endothelial cells to
      hydrostatic pressure.

PMID- 8253873
TI  - Modulatory effect of cyclic AMP on calcium fluxes in FRTL-5 cells.
AB  - The aim of the present study was to investigate the effect of cAMP on calcium
      fluxes in Fura 2 loaded thyroid FRTL-5 cells. Preincubating the cells with the
      phosphodiesterase inhibitor Ro-201724 decreased the ATP-stimulated entry of
      calcium, while having no effect on the release of sequestered calcium.
      Pretreatment with forskolin decreased both the release of sequestered calcium and
      the entry of calcium in response to ATP. We then incubated the cells with
      phenylisopropyl adenosine (PIA), a P2i-receptor agonist earlier shown to decrease
      cAMP in FRTL-5 cells. Although we did not observe a decrease in cellular cAMP
      after PIA, the ATP-evoked calcium response was enhanced. Forskolin decreased
      calcium entry induced by thapsigargin, a Ca(2+)-ATPase inhibitor, but forskolin
      had no effect on the thapsigargin-evoked release of sequestered calcium. Addition
      of calcium to cells stimulated with ATP in a calcium-free buffered resulted in a
      rapid influx of calcium. This response in [Ca2+]i was decreased in cells
      pretreated with forskolin. In cells stimulated with thapsigargin, the increase in
      [Ca2+]i after addition of calcium was inhibited in part by forskolin and enhanced
      by PIA. The results suggest that cAMP may regulate calcium fluxes in FRTL-5
      cells. Furthermore, PIA increased agonist-induced calcium entry through a
      presently unknown mechanism.

PMID- 8253874
TI  - Isoproterenol- and insulin-induced hyperpolarization in rat skeletal muscle.
AB  - Using conventional microelectrode techniques, we investigated the combined
      effects of isoproterenol (Iso) and insulin (Ins) on the resting membrane
      potential (RMP) of isolated rat skeletal muscles. In soleus muscle, Iso (1
      microM) and Ins (4 units/L) separately induced a hyperpolarization of 9.2 mV and
      4.8 mV, respectively. Combined administration of Iso and Ins induced a
      hyperpolarization of 12.4 mV, larger than either one separately. A similar
      observation was made in Na(+)-loaded rewarming experiments. 8-Br-cAMP (1 mM and 3
      mM) and forskolin (10 microM, an adenylate cyclase activator) induced a
      hyperpolarization of 5.3 mV, 8 mV, and 6.0 mV, respectively. This hyperpolarizing
      action was blocked by ouabain, indicating that the Na-K pump was involved in the
      hyperpolarization. 8-Br-cGMP (3 mM) had no effect on RMP; however, it blocked or
      reversed the hyperpolarization caused by 8-Br-cAMP (1 mM). In addition, 8-Br-cGMP
      partially inhibited the hyperpolarizing effect of Iso (1 microM) by 40% and
      completely prevented the effect of Ins. The phorbol ester, PMA, (1 microM, a PKC
      activator) induced a ouabain-inhibitable hyperpolarization. These results suggest
      that cAMP and PKC are involved in the Iso- and Ins-induced hyperpolarization and
      that Iso and Ins influence the RMP presumably through regulation of the
      electrogenic Na-K pump via different mechanisms.

PMID- 8253875
TI  - Flow cytometry reveals different lag times in rapid cytoplasmic calcium
      elevations in human neutrophils in response to N-formyl peptide.
AB  - Flow cytometric analyses were performed to study intracellular single-cell
      calcium transients ([Ca2+]i) in suspended human neutrophils during the initial
      phase of N-formyl peptide stimulation. Thereby, two neutrophil populations became
      apparent. Early maximally Ca(2+)-responding (high fluorescence) neutrophils and
      not-yet Ca(2+)-responding (low fluorescence) neutrophils, but no neutrophils with
      intermediate levels of [Ca2+]i were detected. Within 7 s the number of low
      fluorescence neutrophils decreased and the number of high fluorescence
      neutrophils increased maximally. This suggests that [Ca2+]i transients occurred
      abruptly in individual neutrophils within a time interval below 1 s. At lower N
      formyl peptide concentrations the lag times of individual neutrophils and the
      interval time of maximal activation of the [Ca2+]i-responding neutrophil
      population increased, however the percentage of [Ca2+]i-responding cells
      decreased. Surprisingly, no influence of the N-formyl peptide concentration on
      the [Ca2+]i-induced fluorescence signal of the individual cell was observed: it
      was always in an almost maximal range or not responding. In parallel, binding
      studies performed with fluorescein-labeled N-formyl peptide revealed that the
      heterogeneity of [Ca2+]i-responding cells cannot be explained by different
      receptor occupancy. In summary, this study demonstrates that [Ca2+]i transients
      induced by N-formyl peptides in suspended individual human neutrophils occur very
      rapidly in an almost "all-or-none manner" and that the mean increasing
      fluorescence signal of a calcium indicator within a whole neutrophil population
      results from varying lag times of the individual cells, rather than from the mean
      simultaneous progress of many cells.

PMID- 8253876
TI  - Human T lymphocytes synthesize the 92 kDa type IV collagenase (gelatinase B).
AB  - In order for T cells to exit the circulatory system, traverse the endothelial
      basement membrane, and arrive in target tissues, these cells must attach to and
      degrade basement membrane proteins. 12-O-tetradecanoylphorbol-13-acetate (TPA)
      has been shown to stimulate lymphoid cell adhesion to basement membrane
      components. We have used TPA to study the ability of human lymphoid cells to
      secrete type IV collagenases, enzymes capable of degrading basement membrane
      proteins. Here, we found that human primary T cells and H-9 lymphoid cells
      synthesize the 92 kDa type IV collagenase (gelatinase B) and TPA stimulates the
      synthesis and secretion of this protease. Peak TPA-stimulated gelatinase B
      secretion and mRNA accumulation were observed 9 hours after TPA treatment, while
      the peak adhesion to type IV collagen was observed only 3 hours after TPA
      treatment. The protein kinase C inhibitor, H-7, inhibited TPA-stimulated
      gelatinase B secretion. Both the primary T cells and H-9 lymphoid cells also
      expressed the mRNA for the tissue inhibitor of metalloproteinase-1 (TIMP-1).
      These data demonstrate that TPA-stimulated lymphoid cells adhere to type IV
      collagen and subsequently synthesize and secrete gelatinase B and TIMP-1. We
      conclude that lymphoid cell extravasation may involve cellular employment of
      adhesion mechanisms prior to degradation of the matrix, which is similar to the
      process of extravasation used by metastatic cells.

PMID- 8253877
TI  - Regulation of amino acid transport and protein metabolism in myotubes derived
      from chicken muscle satellite cells by insulin-like growth factor-I.
AB  - The effects of insulin and insulin-like growth factor-I (IGF-I) on amino acid
      transport and protein metabolism were compared in myotubes derived from chicken
      breast muscle satellite cells. Protein synthesis was assessed by continuous
      labelling with [3H]-tyrosine. Protein degradation was estimated by the release of
      trichloroacetic acid (TCA) soluble radioactivity by cells which had been
      previously labelled with [3H]-tyrosine for 3 days. Amino acid transport was
      measured in myotubes incubated in Dulbecco's modified Eagle's medium (DMEM) 0.5%
      bovine serum albumin (BSA) with or without insulin or IGF-I. Subsequent [3H]
      aminoisobutyric acid (AIB) uptake was then measured in amino acid-free medium.
      IGF-I was more efficient than insulin at equimolar concentration (3.2 nmol/l) in
      stimulating protein synthesis (127 and 113% of basal, respectively) and
      inhibiting protein degradation (32% and 13% inhibition of protein degradation
      following 4 h incubation). Half maximal effective concentrations for stimulation
      of AIB uptake were 0.27 +/- 0.03 nmol/l and 34.8 +/- 3.1 nmol/l for IGF-I and
      insulin respectively, with maximal stimulation of about 340% of basal.
      Cycloheximide (3.6 mumol/l) diminished IGF-I-stimulated AIB uptake by 55%.
      Chicken growth hormone had no effect on basal AIB uptake in these cells and
      neither glucagon nor dexamethasone had an effect on basal or IGF-I-stimulated AIB
      uptake. This study demonstrates an anabolic effect for IGF-I in myotubes derived
      from primary chicken satellite cells which is mediated by the type I IGF
      receptor, since the cation-independent mannose 6-phosphate receptor does not bind
      IGF-II in chicken cells.

PMID- 8253878
TI  - Deducing molecular similarity using Voronoi binding sites.
AB  - We have devised a new measure of molecular similarity with respect to given
      simple partitions of space into regions. The similarity is determined by
      numerical integration of the difference in the optimal interaction between the
      two molecules and the regions over a large range of interaction parameter values.
      Compounds differing in empirical formula are differentiated by a single infinite
      region; cis/trans or ortho/meta/para isomers are distinguishable by two adjacent
      regions that are half-spaces; and stereoisomers require five regions. This can be
      viewed as a natural classification of isomers. The concept can also be applied to
      drug binding studies to determine which molecules may bind alike in a given
      biological receptor and to elucidate a necessary starting geometry when a binding
      site is modeled for inhibitors whose experimental binding energies are different.

PMID- 8253879
TI  - [Surgical treatment of secondary hyperparathyroidism in chronic kidney failure.
      Results of total parathyroidectomy with parathyroid autotransplantation].
AB  - Between 1978 and 1990, 68 patients, operated on for secondary hyperparathyroidism
      (HPT), received a forearm intramuscular free autologous parathyroid graft (37
      women and 31 men--mean age: 43 +/- 16 years). The transplantation (Wells
      technique) was performed in the same time as the total parathyroidectomy and the
      remaining parathyroid material after surgical resection was cryopreserved. The
      results were evaluated in term of clinical and/or radiological and/or biological
      response respectively 3 or 5.5 years later, depending of the realisation of a
      renal transplantation (n = 27) or not. Four patients were lost to follow-up and 4
      died post-operatively, including a wrong diagnosis (60 patients evaluated).
      Mortality rate was 12% (5 cases out of 7 related to chronic renal insufficiency).
      In 3 patients (5%) the transplanted gland had to be removed because of recurrent
      HPT (1 graft hyperplasia; 2 wrong diagnosis: 1 cervical gland left over and 1
      aluminium intoxication). Second cervicotomy was performed in 3 cases (5%) for
      remaining cervical parathyroid gland (2 cases) and false-positive Tallium
      Technetium scan (1 case). Overall results were good or very good in 51 cases
      (85%). A review of the literature indicate that subtotal parathyroidectomy in not
      superior to the Wells technique and the latter remain the landmark technique in
      the authors' hands in order to treat secondary HPT.

PMID- 8253880
TI  - [Surgical approaches to segment I for malignant tumors (20 cases)].
AB  - Seven complete and 13 partial resections of segment I (caudate lobe) were
      performed for malignant tumors. In all except one instance, removal of segment I
      was combined with other types of hepatic resection for technical or carcinologic
      reasons. Six were iterative hepatic resections for recurrent hepatic metastases.
      In two, the future remaining left lobe was hypertrophied by right portal venous
      embolization preoperatively. Hepatectomies were performed with intermittent
      portal triad clamping (mean total duration of 63 minutes, range of 20 to 120
      minutes) and after preparation for total vascular exclusion. Associated partial
      resection of the inferior vena cava was necessary in three instances. Mean
      duration of operation was 285 minutes (range of 60 to 540 minutes) and mean blood
      loss was 1,749 milliliters (range of 200 to 5,200 milliliters). There was no
      postoperative mortality and the morbidity rate was low. Surprisingly, we
      discovered retrospectively that free margins were small (less than 5 millimeters)
      in 83 percent of the patients. Regardless of limited free margins and six
      iterative hepatectomies, eight patients were free of disease with a mean follow
      up examination period of 19.2 months. Technical problems were different for each
      patient and a patient by patient adaptation was necessary. Left, right and
      central approaches were used accordingly. If resection of segment I associated
      with a right of left hepatectomy can currently considered as a standard hepatic
      resection, isolated complete resection of segment I remains a real technical
      challenge.

PMID- 8253881
TI  - [Ruptures of the bladder. Surgical or conservative treatment].
AB  - Since the bladder is well protected by the bony pelvis, it is seldom injured.
      However, the initial trauma may be a major one, and associated lesions are
      frequent, especially in case of extraperitoneal ruptures. Retrograde cystography
      still remains an essential examination, for which the technique must be
      straightforward. This work is a review of our cases of pure bladder rupture from
      1981 to 1992. Investigations, treatment, and our results are discussed, and the
      literature is reviewed. In the last few years, we have been favoring a
      conservative approach of extraperitoneal lesions.

PMID- 8253882
TI  - [Reoperation of tumors of the parotid gland, surgical approach and consequences
      for the 7th cranial nerve. Apropos of 42 cases].
AB  - Second or more surgical procedures on parotid are usually difficult and may
      induce injury on the facial nerve. The authors report their experience about 42
      patients. The choice between a total parotidectomy or a surgical excision of a
      tumor depends on the number of surgical procedure, the type of initial procedure
      and the histological type of the tumor. Second surgical procedures for a wrong
      initial diagnosis (11 cases) were always a total parotidectomy with facial nerve
      preservation. The risk of a partial or total facial palsy is higher after several
      recurrences (3 of 8 cases). The facial nerve had to be resected in 3 of 9 cases
      of malignant tumors recurrences. The initial treatment of a tumor of the parotid
      must be radical so it can prevent for further surgical procedures and then avoid
      a facial nerve injury.

PMID- 8253883
TI  - [Role of surgery in the treatment of severe acute necrotic pancreatitis].
AB  - Between May 1975 and December 1991, a total of 208 patients were operated upon
      for severe acute necrotic pancreatitis. The decision whether to operate on
      patients with clinical and biologic aggravation despite particularly sustained
      intensive care was taken after evaluation of ultrasound and CT scan images.
      Combining pancreatic body resections and necrotic tissue excision with
      laparostomy and staged lavage drainage reduced global mortality rate from 49.2 to
      16.4 p. cent. The criteria used for determining the indication for surgical
      intervention, and the technical and tactical operative procedures applied
      allowing this improvement, are described and discussed.

PMID- 8253884
TI  - [Malignant lymphoma complicating Crohn disease of the ileum. Apropos of a case].
AB  - The association of cancer and Crohn's disease is well documented and comprises 2%
      of cases, but the onset of a malignant lymphoma during the course of the disease
      is a very rare finding (20 cases reported). A patient presented with a malignant
      plasmocytic lymphoma complicating an ileal Crohn's affection. Both clinical and
      radiological diagnosis were uncertain, most such cases being discovered
      perioperatively, confirmation of the diagnosis being provided by histology and
      immunohistology, which also allow classification of the lymphoma to allow
      adaptation of complementary postoperative treatment.

PMID- 8253886
TI  - [Urethrocele in males].
AB  - Concerning one case of male urethral diverticulum, the characteristics of this
      rare affection are reviewed. Carriage for long time of urethral catheter and
      urethroplasty are the more frequent etiologies of this affection. The diagnosis
      is clinic, based on the discovery of tumefaction on the urethral track which
      pression makes spring up urine through urethral meatus. The urethrography
      confirms the diagnosis. Surgical approach consists on the resection of the
      diverticulum and urethrorrhaphy in one or two stages, based on diverticular neck
      size and sheet quality.

PMID- 8253885
TI  - [Thoracic traumas and wounds in Libreville. Therapeutic aspects. Apropos of 106
      cases].
AB  - 106 cases of trauma and chest wounds have been treated at the Jeanne Ebori
      Foundation from 1980 to 1990. They involved 90 men (85%) and 16 women (16%) with
      an average age of 35. The prevalent etiology was road accidents 55 (52%),
      followed by assaults 30 (28%). 22 blade wounds and 12 bullet wounds required
      coordinated surgical and intensive care at resuscitation. 19 pleuro-mediastinal
      spills, 8 intra-thoracic lesions with 6 vascular wounds and 1 heart wound.
      Surgical treatment required 13 immediate thoracotomies and in 3 cases with 1
      associated laparotomy. We recorded 8 deaths (7%), 75 healings without
      consequences (71%) and 23 healings with consequences (22%). We noted the extreme
      gravity of the penetrating wounds especially bullet wounds, as well as that of
      the poly-traumatisms. This picture requires complex resuscitation management with
      surgical relays in a precarious respiratory context.

PMID- 8253887
TI  - [The musculocutaneous flap of the latissimus dorsi in the treatment of
      recurrences of breast cancer].
AB  - Breast cancers local recurrence treatment usually requires a large chirurgical
      resection. Latissimus dorsi myocutaneous flap was used after mastectomy in 27
      patients. This technique was performed in 14 patients who had a recurrence after
      exclusive radiotherapy treatment. The follow-up of all the patients was more than
      5 years. A 42% survival rate has been quoted in this group, after a 11 years
      period. Latissimus dorsi myocutaneous flap seems to be a satisfactory alternative
      when performing reconstruction after wall excision under 300 cm2, excepted for
      recurrence of fast kinetic cancers.

PMID- 8253888
TI  - [Treatment of a neglected traumatic perforation of the cervical esophagus by a
      muscular flap from the sterno-cleido-mastoid muscle. Apropos of a case].
AB  - The diagnosis and management of oesophageal perforation is quite a problem. When
      the perforation is diagnosed early, treatment is easy with subsequently good
      results. When the diagnosis is delayed, treatment become complex, with a
      morbidity rate of about 35% and a high morbidity. This simple case report,
      describe the use of a sternocleido-mastoid muscle flap in the repair of a
      traumatic cervical oesophageal perforation with important loss of substance.

PMID- 8253889
TI  - [Traumatic luxation of the testis].

PMID- 8253891
TI  - Fulfilling Lawrence Weed's vision.

PMID- 8253890
TI  - [Benign schwannoma of the anterior tibial nerve: apropos of a case complicated by
      an encysted hematoma].

PMID- 8253892
TI  - The uncontrollable epidemic of 2010?

PMID- 8253893
TI  - Paper-bag rebreathing.

PMID- 8253894
TI  - Case in point. Linitis plastica (leather bottle stomach).

PMID- 8253895
TI  - Ptosis and headache in an i.v. drug abuser.

PMID- 8253896
TI  - Reductionism is not a dirty word.

PMID- 8253897
TI  - Tracing the cause of dyspnea.

PMID- 8253898
TI  - Global T-wave inversion after a car accident.

PMID- 8253899
TI  - Disseminated tuberculosis: a presumptive diagnosis.

PMID- 8253901
TI  - 1960-1992, Volumes 1-33. Cumulative contents and author index.

PMID- 8253900
TI  - Case in point. Sliding hiatal hernia.

PMID- 8253903
TI  - [Studies on the factors affecting the prognosis of patients with metastatic brain
      tumors].
AB  - The factors affecting the prognosis of 85 patients with brain metastases from
      August 1973 to August 1992 were analyzed. The following specific factors were
      reviewed; (1) patient age, (2) primary site, (3) disease free interval, (4)
      presence or absence of disseminated disease, (5) initial neurological symptoms
      (focal signs or IICP signs), (6) single or multiple metastases, and (7) treatment
      (surgery, chemotherapy, radiotherapy, locally injected chemotherapy). Statistical
      evaluation of the various prognostic factors was performed on the basis of the
      mean survival time and the survival rate after brain metastasis. The overall mean
      survival time after brain metastasis was 8.2 months. Regarding the cause of
      death, only 35% of nonsurvivors died of the brain lesion itself, while 38% died
      because of systemic cancer. The group with focal signs as the initial
      neurological symptoms had a mean survival time of 11.9 months versus 5.2 months
      for the IICP signs group. The focal signs group also had a significantly better
      survival rate compared to the IICP group (p < 0.01). Evaluation of the prognosis
      in relation to therapy showed that locally injected chemotherapy and intravenous
      chemotherapy tended to prolong survival, but did not significantly increase the
      survival rate. However, surgery and radiotherapy achieved a longer survival time
      and significantly improved the survival rate (p < 0.05 for surgery and p < 0.01
      for radiotherapy). It is concluded that the significantly favorable prognostic
      variables were focal signs as the initial neurological symptoms, surgical
      treatment, and radiotherapy.

PMID- 8253902
TI  - [Correlation between adherence ability and construction of basement membrane-like
      scaffold of HeLa-S3 cells in nude mouse tumor].
AB  - We selected a subclone of HeLa-S3 cells to depict the relationship between
      cellular adherence to the extracellular matrix and pathological features of
      tumors derived from these cells. The selected subclone (PA cells) adheres poorly
      to type-IV collagen as compared to the wild type cells (EA cells) which attach
      easily to type-IV collagen. In vitro, it was confirmed that PA cells adhered
      poorly to type-IV collagen even after a long term of culture and showed weaker
      chemotactic activity toward this BM component. Injected into nude mice, PA cells
      formed smaller tumors than EA cells. Histologically, both derived tumors showed
      construction of basement membrane-like scaffolds that stained positively for type
      IV collagen and laminin. EA cell tumors demonstrated frequent absence of and
      thinning and gaps in their basement membrane, which shows the invasive activity
      of the tumors. PA cell tumors showed a more regular basement membrane with
      predominant desmoplasia.

PMID- 8253904
TI  - [Surgical stress and opsonic activity].

PMID- 8253905
TI  - [Surgical stress and lymphocyte function. Effects of PSK to prevent cellular
      immunosuppression].

PMID- 8253906
TI  - [Heterogeneous aging of macrophages in mice].

PMID- 8253907
TI  - [Tissue injury by free radicals after surgical stress].

PMID- 8253908
TI  - [Host defense mechanism and hematolymphoid system of the liver. Dynamic changes
      of the hematolymphoid system during liver regeneration].

PMID- 8253909
TI  - [A study on AIDS knowledge initial report. Investigation of nurse school and
      university students].

PMID- 8253910
TI  - [Imaging diagnosis of malignant lymphoma in the gastrointestinal tract].

PMID- 8253911
TI  - [Treatment of stroke].

PMID- 8253912
TI  - An experimental study on wound healing in hypothyroidism.

PMID- 8253913
TI  - Egg donation to women over 40 years of age.

PMID- 8253914
TI  - Pregnancy after the menopause: a challenge to nature?

PMID- 8253915
TI  - A poisoned inheritance to our children.

PMID- 8253916
TI  - Enhanced sensitivity of the extrinsic coagulation system during ovarian
      stimulation for in-vitro fertilization.
AB  - The tissue factor activity in blood monocytes was investigated during ovarian
      stimulation for in-vitro fertilization (IVF) in 13 women. Blood samples were
      taken prior to hormonal stimulation (days 2-3 of the menstrual cycle, median
      serum oestradiol concentration 70 pmol/l) and the day after ovulation induction
      with human chorionic gonadotrophin (days 11-13, median serum oestradiol
      concentration 6270 pmol/l). The tissue factor activity in unstimulated monocytes
      and factor VII concentration were unchanged during the treatment. However, the
      tissue factor activity in lipopolysaccharide-stimulated monocytes was on average
      more than twice as high after stimulation (P < 0.02). A positive correlation was
      found between the tissue factor activity and the serum concentration of
      oestradiol (r = 0.514, P < 0.02). The tumour necrosis factor (TNF)-alpha
      increased during ovarian stimulation (P = 0.05), and there was a positive
      correlation between the change in TNF-alpha and the change in tissue factor
      activity (r = 0.663, P < 0.05). Our results indicate an enhanced sensitivity of
      the extrinsic coagulation system during IVF treatment since more tissue factor is
      available upon stimulation. It is suggested that this may be important in
      thrombotic situations. Further studies are necessary to elucidate the mechanism
      behind this response.

PMID- 8253917
TI  - The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian
      multicentric study. I. Clinical and biological features.
AB  - The multicentric study regroups 128 cases of the ovarian hyperstimulation
      syndrome (OHSS) in in-vitro fertilization (IVF) and 256 selected controls. Values
      of serum oestradiol obtained from different laboratories were found to be
      normally distributed after logarithmic transformation. Comparative study of
      clinical and biological characteristics indicates that among OHSS patients (i)
      mean age was lower; (ii) tubal indications for IVF were less frequent; (iii)
      polycystic ovary-like conditions (i.e. hyperandrogenism, anovulation, luteinizing
      hormone/follicle stimulating hormone ratio > 2) were more frequent. OHSS patients
      displayed ovarian hypersensitivity reflected by higher oestradiol peak
      concentrations in response to lower dosage of human menopausal gonadotrophin and
      by a steeper slope of oestradiol increment during stimulation. In these patients,
      the collection of greater numbers of fertilizable oocytes allowed replacement of
      more embryos with a good vitality score. Ongoing pregnancy rate was found to be
      higher among the OHSS patients. The following complications were recorded among
      OHSS cases: abdominal fluid at echographic examination or clinical ascites (86.7
      and 71.1%, respectively); pleural and pericardial effusion (21 and 3%,
      respectively); haemoconcentration (71.1%); electrolytic disorders (6.2%).
      Although significantly different between groups, clinical and biological
      parameters under study showed considerable overlap of their distributions in
      control and OHSS cases. Therefore, these data must be submitted to discriminant
      analysis in order to derive a formula predictive of the risk of OHSS.

PMID- 8253918
TI  - The ovarian hyperstimulation syndrome in in-vitro fertilization: a Belgian
      multicentric study. II. Multiple discriminant analysis for risk prediction.
AB  - The considerable overlap of distributions of values for different parameters
      between control and ovarian hyperstimulation syndrome (OHSS) populations makes
      any single variable inefficient for risk prediction. Combinations of variables
      were studied in a discriminant function in order to increase predictivity and
      decrease the false negative rate. Such analyses were performed on two groups of
      in-vitro fertilization (IVF) patients: all OHSS cases (n = 128) (group A) and
      only severe OHSS cases (n = 92) (group B). Progressive introduction and automated
      stepwise selection of variables were applied to both groups. The best prediction
      (78.5%) was obtained in group A under post-oocyte retrieval conditions using log
      oestradiol, slope of log oestradiol increment, human menopausal gonadotrophin
      (HMG) dosage, number of oocytes retrieved and ratio of luteinizing
      hormone/follicle stimulating hormone (LH/FSH), in the formula. The corresponding
      false negative rate was 18.1%. However, effective prevention of OHSS implies the
      ability to withhold human chorionic gonadotrophin injection. Therefore a formula
      for pre-oocyte retrieval conditions was established yielding a prediction rate of
      76.1% with a false negative rate of 18.1%. To be validated, such formulae have to
      be applied to another population of IVF cases used as a 'testing-set'.

PMID- 8253919
TI  - The choice of treatment for anovulation associated with polycystic ovary syndrome
      following failure to conceive with clomiphene.
AB  - The choice of treatment for clomiphene-resistant anovulation associated with
      polycystic ovary syndrome (PCOS) is presently arbitrary and selection criteria
      are not available. A total of 144 women with anovulatory infertility associated
      with PCOS who failed to conceive on clomiphene were treated with either pure
      follicle stimulating hormone (FSH) (n = 29), or human menopausal gonadotrophin
      (HMG) (n = 60), or gonadotrophin-releasing hormone analogue (GnRHa) and HMG (n =
      55). Analysis of 306 treatment cycles and 53 pregnancies revealed a cumulative
      conception rate at 4 months of 23% with FSH, 47% with HMG and 69% with GnRHa +
      HMG. The miscarriage rate was highest in the HMG group (44%) and consequently the
      cumulative live birth rate was superior when GnRHa was used in combination with
      HMG. There were no significant differences in the basal clinical and
      endocrinological features of those who conceived compared with those who did not,
      either in the whole group, or in the individual treatment groups. Thus, the
      choice of treatment for clomiphene-resistant women with PCOS cannot be guided by
      the basal clinical or endocrinological features of this heterogeneous syndrome
      with the present state or knowledge.

PMID- 8253920
TI  - Human chorionic gonadotrophin is a better luteal support than progesterone in
      ultrashort gonadotrophin-releasing hormone agonist/menotrophin in-vitro
      fertilization cycles.
AB  - In an attempt to determine the best luteal support in in-vitro fertilization
      (IVF) cycles treated with gonadotrophin-releasing hormone agonist (GnRHa) and
      human menopausal gonadotrophin (HMG) by the ultrashort protocol, 60 patients were
      prospectively randomized for either i.m. progesterone or human chorionic
      gonadotrophin (HCG) luteal support. The two groups did not differ in the mean
      number of oocytes retrieved and embryos replaced, nor in the mean age of the
      patients and the amount of HMG used. HCG maintained higher levels of oestradiol
      and progesterone during the luteal phase. Conception rate was significantly
      higher in the HCG group. We conclude that HCG is superior to i.m. progesterone as
      luteal support in IVF cycles in which GnRHa is used in the ultrashort protocol.

PMID- 8253921
TI  - Pre-ovulatory progesterone growth rate in patients treated with gonadotrophin
      releasing hormone agonist and outcome of in-vitro fertilization.
AB  - The present study was undertaken to assess whether the increase in serum
      progesterone concentration following the administration of human chorionic
      gonadotrophin (HCG) may have predictive value on the in-vitro fertilization (IVF)
      success rate. Progesterone concentration on the day of HCG administration and the
      increase in progesterone concentration on the following day were evaluated in 140
      consecutive patients undergoing IVF with embryo transfer. Stimulation protocol in
      all study patients entailed intranasal administration of short-acting
      gonadotrophin-releasing hormone agonist (GnRHa) buserelin and human menopausal
      gonadotrophin. A pregnancy rate of 37.2% was achieved when at least three embryos
      were transferred. The only significant difference between conception and non
      conception cycles was found in serum progesterone concentrations after HCG
      administration (P < 0.01), whereas the mean progesterone concentration on the day
      of HCG did not differ. No difference in other hormonal or cycle parameters was
      observed. The increase in progesterone concentration was significantly greater in
      the group of patients who achieved pregnancy than in the group who did not (2.2
      +/- 0.2 versus 1.6 +/- 0.1 ng/ml, respectively; P < 0.01). A critical breakpoint
      in serum progesterone was arbitrarily determined at 1 ng/ml. An increase in
      progesterone concentration > or = 1 ng/ml when three or more embryos were
      transferred was associated with a positive predictive value for pregnancy of
      40.4% (sensitivity of 94.7%), whereas a negative predictive value of 86.7% was
      obtained when this value was < 1 ng/ml. These findings indicate that an adequate
      rise in serum progesterone following HCG administration provides useful
      information about the possible outcome of the treated cycle.

PMID- 8253922
TI  - Development of a human granulosa cell culture model with follicle stimulating
      hormone responsiveness.
AB  - In order to study the effects of follicle-stimulating hormone (FSH) on
      differentiation of granulosa cells, a well-defined and validated in-vitro culture
      system is indispensable. In this study, pooled follicular aspirates were
      stimulated in vitro with FSH and luteinizing hormone (LH) for 2, 4 and 6 days,
      either immediately after plating or after 7 days of preincubation. Cultures were
      assayed for progesterone and oestradiol production. Fresh cells displayed very
      high basal progesterone production which could be stimulated with LH but not FSH.
      After preincubation, addition of LH and FSH resulted in dose-dependent increases
      of progesterone and oestradiol. When cultured on human fibronectin-coated wells,
      similar basal but higher progesterone concentrations after stimulation were
      observed. In comparison with serum-free media, addition of Serum-Plus resulted in
      higher basal and stimulated progesterone concentration, possibly due to the
      presence of serum factors. This study demonstrates firstly that after 7 days
      preincubation, cultures gained responsiveness to FSH but remained responsive to
      LH during 4 days of stimulation. This suggests a persisting differentiated cell
      population in vitro. Secondly, the use of human fibronectin extracellular matrix
      and serum promotes steroid production, either due to factors promoting cell
      growth and function or to availability of steroid precursors. Therefore one has
      to be cautious with interpretation of data obtained from this widely used culture
      system, employing highly differentiated cells obtained after ovarian stimulation
      for in-vitro fertilization for study of local regulation of granulosa cell
      function.

PMID- 8253923
TI  - Different follicle stimulating hormone/luteinizing hormone ratios for ovarian
      stimulation.
AB  - The aim of the present study was to investigate whether reducing the amount of
      luteinizing hormone (LH) in gonadotrophic preparations impairs follicular growth
      in in-vitro fertilization (IVF) cycles during suppression of endogenous LH
      levels. A selected group of 20 IVF patients was randomly divided into two groups.
      One group was treated with Org 31338 [follicle stimulating hormone (FSH)/LH 3:1],
      the other group with Metrodin (purified FSH), both during pituitary down
      regulation with buserelin. A fixed daily dose of 150 IU FSH i.m. was given. Serum
      concentrations of FSH, LH, oestradiol and progesterone were determined frequently
      and serial ultrasound examinations were performed. Multiple follicular growth
      with concomitant rise of oestradiol levels was observed in all cycles. The
      duration of the stimulation phase was shorter in the group treated with Org 31338
      than in the group treated with Metrodin. The number of follicles and oocytes and
      the fertilization rate was larger and the mean embryo quality was higher in the
      Org 31338 group, but the differences did not reach statistical significance. No
      significant differences were found in hormonal values. In women with normal
      endocrine profiles, lowering of the LH activity in gonadotrophic preparations
      during gonadotrophin-releasing hormone agonist treatment results in adequate
      ovarian stimulation. However, a preparation with some LH needed a shorter
      stimulation than a purified FSH preparation. Whether the other beneficial effects
      of Org 31338 also occur in a larger population needs further investigation.

PMID- 8253924
TI  - Presence and possible function of activin-like substance in human follicular
      fluid.
AB  - We assessed the presence of an activin-like substance in human follicular fluid
      that was obtained from women undergoing in-vitro fertilization using a bioassay
      for activin A. Activin activity was not detected in crude follicular fluids; the
      bioactivity of standard activin A was inhibited by the addition of follicular
      fluid. After the follistatin (binding protein of activin A) was removed from
      follicular fluid using a purification procedure, activin activity was detected in
      the follicular fluids (mean concentration: 131 +/- 40 ng/ml). Activin activity
      was inhibited by the addition of follistatin to fluid. The concentration of
      activin activity was substantially higher (approximately 100-fold) than that
      reported in serum. The concentration negatively and significantly correlated with
      the number of developed follicles in the ovary (r = 0.501, P < 0.01). These
      results suggest that activin A and its binding protein are present in follicular
      fluid in large amounts and that they may have a role in local ovarian regulation.

PMID- 8253925
TI  - Endometrial microvascular density during the normal menstrual cycle and following
      exposure to long-term levonorgestrel.
AB  - The mechanisms that underlie progestogen-induced endometrial breakthrough
      bleeding are poorly understood. The aim of the present study was to quantify
      endometrial microvascular density in 54 controls and 42 women with 3-12 months'
      exposure to Norplant (levonorgestrel subdermal contraceptive implant) and to
      correlate it with bleeding pattern, endometrial histology, and peripheral plasma
      oestradiol and progesterone concentrations. Endometrial biopsies were processed
      routinely and sections immunostained using anti-CD34 antibody to identify
      vascular endothelial cells. Menstrual record card data were analysed using World
      Health Organization definitions. The mean microvascular density (+/- SEM) for
      control samples was 186 +/- 8 vessels/mm2, and there were no significant
      differences across the cycle. Norplant user's endometrial microvascular density
      was significantly elevated above controls (294 +/- 18 vessels/mm2, P = 3.36 x 10(
      8)). Endometrial microvascular density in Norplant users did not correlate with
      oestrogen concentrations prior to biopsy, bleeding patterns or endometrial
      histology. The results from this study show that women receiving Norplant have
      significantly increased endometrial microvascular density compared to controls.
      Another finding from this study was that bleeding in Norplant users often
      occurred from thin atrophic endometrium. These results provide new insights into
      the physiological mechanisms that may be involved in progestogen-induced
      endometrial bleeding.

PMID- 8253926
TI  - Determination of antisperm antibodies in serum samples by means of enzyme-linked
      immunosorbent assay--a procedure to be recommended during infertility
      investigation?
AB  - The clinical significance of antispermatozoal antibody (ASA) testing in serum
      samples with an enzyme-linked immunosorbent (ELISA) technique using a
      commercially available kit was evaluated in 95 randomly chosen couples under
      infertility investigation. Results were related to many other parameters of male
      and female fertility, e.g. outcome of sperm analysis, testing of sperm functional
      capacity including the crossed in-vitro sperm-cervical mucus penetration test
      (SCMPT), results of a microbial screening in genital secretions, testing for
      local IgG- and IgA-class sperm antibodies in semen by means of the mixed
      antiglobulin reaction (MAR) and the subsequent pregnancy rate in a prospective
      study. Results of ASA testing did not show any relationship with medical history
      and results of clinical examination, the semen quality including sperm function
      tests and seminal cultures, outcome of the crossed SCMPT, and local ASA. All
      patients with MAR (IgG or IgA) positive ejaculates were ELISA negative in serum
      samples. No significant difference with regard to circulating ASA (ELISA) was
      found in couples with and without a subsequent pregnancy. Furthermore there was
      no significant difference of antibody levels in subfertile female patients,
      virgins (n = 36), 'normal' pregnant women (n = 39) and prostitutes (n = 40). In
      summary, the results of this study clearly demonstrate that the use of this
      method for detection of antisperm antibodies during infertility investigation
      cannot be recommended.

PMID- 8253927
TI  - Formation of antisperm antibodies in women treated with fallopian tube sperm
      perfusion.
AB  - Fallopian tube sperm perfusion (FSP) is a combination of ovarian stimulation and
      intra-uterine insemination using a large volume (4 ml) of inseminate containing
      10(7)-10(8) spermatozoa. The inseminate will flush the Fallopian tubes and some
      of it will end up in the pouch of Douglas. In the present study, we have
      investigated whether the FSP method will result in the formation of serum
      antisperm antibodies in the female. A total of 184 treatment cycles were given to
      128 women. The indications for treatment were: unexplained infertility (n = 35),
      various infertility diagnoses (n = 28) and donor insemination (n = 65). Prior to
      treatment, 11 (8.6%) women had a positive tray-agglutination test (Friberg)
      and/or a positive immunobead test. After completing one to four treatment cycles,
      another six (4.7%) women had developed serum antisperm antibodies. The antibodies
      induced by the treatment were of isotype IgM and directed against the tail-tip of
      the spermatozoa. Two of the women, who prior to the treatment had antisperm
      antibodies, showed an increase in antibody titre during treatment. There was no
      statistically significant difference in the pregnancy rate between the women with
      antisperm antibodies and the women without. In our opinion, the small risk of
      developing antisperm antibodies is no contra-indication for treating infertile
      couples with FSP.

PMID- 8253928
TI  - Glandular distribution of immunoglobulins, J chain, secretory component, and HLA
      DR in the human endometrium throughout the menstrual cycle.
AB  - Two-colour immunofluorescence was used to study components of the secretory
      immune system in the endometrium. Tissue sampling was performed in the
      follicular, ovulatory and luteal menstrual phase from women admitted for
      laparoscopic sterilization. The specimens were prepared for immunohistochemistry
      by a method that removes most extracellular immunoglobulin (Ig). The stroma
      contained only a few Ig-producing immunocytes, but was rich in HLA-DR positive
      cells. Most of the IgA- and IgM-producing immunocytes also expressed J chain,
      which is necessary for the generation of polymeric Ig (poly-Ig) with affinity for
      epithelial secretory component (SC or poly-Ig receptor). Throughout the menstrual
      cycle there was increasing accumulation of Ig within the endometrial glands, with
      preferential apical and intraluminal occurrence of IgA and IgM, usually along
      with J chain and SC. It is likely that some monomeric IgA (without J chain) and
      IgG enter the endometrial glands by passive diffusion from the stroma, but there
      is clearly an additional active external poly-Ig transport. Some of the glands
      stained for HLA-DR irrespective of the menstrual phase or degree of SC
      expression. Our findings suggest that active SC-mediated external transport of
      serum-derived (and to some extent locally produced) poly-Ig is enhanced in the
      luteal phase, and that SC and HLA class II molecules are differently regulated in
      the endometrial glands.

PMID- 8253929
TI  - Assessments of embryo transfer after in-vitro fertilization: effects of glyceryl
      trinitrate.
AB  - The role of embryo transfer and its associated difficulties on the outcome of
      human in-vitro fertilization (IVF) were examined using a standardized procedure
      and a scoring system (embryo transfer scores 1-5). This system was used to assess
      any effects of the smooth muscle relaxant glyceryl trinitrate (GTN) on embryo
      transfer. Patients (n = 120) were randomized in a double-blind manner at their
      first embryo transfer to receive sublingual GTN or placebo before the transfer.
      Retrospective analysis showed that higher pregnancy rates were associated with
      uncomplicated transfers (score 1; P < 0.01). The outcome measures included
      pregnancy rate, total time of cervical manipulation (embryo transfer time) and
      embryo transfer score. All pregnancies had a transfer score of 1 or 2, but no
      recorded parameter differentiated between pregnant or non-pregnant cycles, and
      GTN had no significant effect on any parameter.

PMID- 8253930
TI  - Histological findings in a falloposcopically retrieved isthmic plug causing
      reversible proximal tubal obstruction.
AB  - We present the case of a 33-year-old woman with a 10 year history of infertility.
      Transvaginal falloposcopy revealed a proximal tubal occlusion (PTO) on the right
      due to a tissue plug. The plug was removed during dilatation of the tubal lumen.
      After the procedure patency for dye was restored. Histological and
      immunohistochemical findings--for the first time, to the best of our knowledge,
      performed in a falloposcopically retrieved plug--revealed the diagnosis of an
      inflammatory polyp arising from the tubal mucosa with focal calcifications. Local
      obstructive inflammatory residues of a previously treated tubal endometriosis,
      which was accompanied by features of salpingitis isthmica nodosa, are considered
      the most likely cause for this condition. Other possible aetiological factors
      responsible for PTO are discussed.

PMID- 8253931
TI  - Results of retroactive testing of human semen donors for cystic fibrosis and
      human immunodeficiency virus by polymerase chain reaction.
AB  - Retroactive testing for cystic fibrosis carrier status was performed on 149 semen
      donors and 100 donor applicants; 162 human immunodeficiency virus (HIV-1) sero
      negative non-active semen donors and 45 HIV-1 sero-negative actively donating
      semen donors were also retroactively tested for HIV-1 by polymerase chain
      reaction (PCR). The 249 individuals tested for cystic fibrosis were examined for
      seven mutations including delta F508, G542X, S549I, S549N, G551D, R553X, and
      W1282X. Of 149 retroactively tested donors, five (3.4%) were determined to be
      heterozygous carriers of the delta F508 mutation for cystic fibrosis. One of the
      100 donor applicants was also heterozygous for delta F508. The 207 HIV-1 sero
      negative donors had an average of 15.4 (range 2-45) HIV antibody tests during an
      average of 15.6 (range 1-68) months of donations. No donors had positive
      seroconversion. These donors also tested negative for HIV by PCR. Cystic fibrosis
      testing of donor applicants prevents known carriers from being used for
      artificial insemination by donor therapy and reduces substantially the risk of an
      offspring being born with the disease. With stringent donor selection and
      exclusion of high-HIV-risk applicants, the occurrence of HIV infection and
      subsequent seroconversion in donor populations should be very infrequent.

PMID- 8253932
TI  - Percoll semen preparation enhances human oocyte fertilization in male-factor
      infertility as shown by a randomized cross-over study.
AB  - The aim of this study was to compare two methods of semen preparation: multiple
      tube swim-up and Percoll separation, using a randomized cross-over clinical
      study, in which sperm parameters, oocyte fertilization rates, embryo quality and
      cell stage were analysed. Overall, there was no difference between the two
      preparation methods in the normozoospermic cycles. In the male-factor cycles,
      Percoll extracted a higher total number of spermatozoa (P = 0.02), increased the
      concentration of motile spermatozoa (P = 0.02), increased the total number of
      motile spermatozoa per sample (P = 0.02), and enhanced the recovery rate of
      motile spermatozoa (P = 0.04) compared to swim-up. There was a significant
      improvement in fertilization rates (P = 0.0006), in the percentage of embryos
      over 2-cell stage on day of transfer (P = 0.004), and in the number of replaced
      embryos per transfer (P = 0.01) in the Percoll as compared to swim-up cycles.
      There was no significant difference in embryo quality. We conclude, therefore,
      that in advanced reproductive procedures where sperm dysfunction exists, semen
      preparation with Percoll should replace the swim-up technique.

PMID- 8253933
TI  - Effects of platelet activating factor on human sperm function in vitro.
AB  - The direct effects of platelet activating factor (PAF) and the specific PAF
      receptor antagonist, CV-3988, on the fertilizing ability of human spermatozoa
      were investigated. PAF (10(-7)-10(-11) M) increased the human sperm penetration
      rates in a sperm penetration assay at all doses > 10(-11) M. In contrast,
      treatment of the spermatozoa with 10(-5) CV-3988 caused a significant decrease in
      human sperm penetration of zona-free hamster oocytes and adversely affected sperm
      motility after 24 h of incubation. This suppression was reversed by the addition
      of PAF. The acrosome reaction was also enhanced by PAF treatment of spermatozoa
      but this effect was not observed in calcium-free medium. While 10(-5) M CV-3988
      decreased the acrosome reaction, the inhibition was also reversed by the addition
      of PAF. These results suggest that PAF may have a direct role in the fertilizing
      capacity of human spermatozoa. These findings also suggest that PAF may have a
      clinical application in an in-vitro fertilization programme.

PMID- 8253934
TI  - Acrosome reaction inducing activity in follicular fluid correlates with
      progesterone concentration but not with oocyte maturity or fertilizability.
AB  - Follicular fluid is a potent mediator of sperm acrosome reaction (AR) in vitro.
      The aim of this study was to investigate whether individual follicular fluids
      vary quantitatively in their ability to stimulate an AR, and whether such
      variability relates to fertilizability of the corresponding egg, its maturational
      level and/or progesterone content. Individual follicular fluids were obtained
      from 24 women undergoing in-vitro fertilization and assayed for their ability to
      induce an AR in normal human spermatozoa. After incubation in capacitation medium
      for 18 h, spermatozoa were challenged with the individual follicular fluids for
      30 min. AR was detected by immunofluorescence, using fluorescein-labelled Pisum
      sativum lectin. We found that individual follicular fluids varied markedly in
      their ability to induce AR. Acrosome reaction correlated linearly with
      progesterone concentration (Spearman's r = 0.735, P = 0.01) at constant protein
      level, but no correlation was found between AR and protein concentration at
      constant progesterone level. Progesterone concentrations were not only higher
      (ANOVA, P = 0.002) in fluids from mature oocytes compared to those from less
      mature or post-mature eggs but also in fluids from fertilized compared to
      unfertilized eggs (ANOVA, P = 0.015, n = 13 patients with both fertilized and
      unfertilized eggs). In contrast, AR-inducing ability of individual follicular
      fluids did not differ for fertilized and unfertilized eggs. While AR-inducing
      ability appeared to increase with maturational stage of the egg, this trend was
      not statistically significant, probably due to small sample size. Our data
      suggest that progesterone rather than protein is the principal mediator of
      acrosome reaction induced by follicular fluid in vitro.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8253935
TI  - Co-culture with granulosa cells does not increase the fertilization rate in
      couples with previous fertilization failures.
AB  - Ten couples included in our in-vitro fertilization programme, selected because of
      one of more previous total fertilization failures or a low fertilization rate (<
      20%), were entered in an experimental protocol of egg insemination on autologous
      granulosa cells. Half the oocytes from each patient were randomly assigned to
      either a control or a co-culture group. We observed no difference in the
      fertilization rate between the control (16.2%) and co-culture groups (12.1%).
      Only two couples benefited from this technique since fertilization was obtained
      only in co-culture. The poor efficiency of this protocol led us to propose the
      use of sperm micro-injection if all classical attempts to improve fertilization
      were unsuccessful.

PMID- 8253936
TI  - The effect of epidermal growth factor on growth and differentiation of mouse
      preimplantation embryos in vitro.
AB  - The effect of epidermal growth factor (EGF) on embryonic growth, development,
      attachment and spreading in vitro was studied. EGF was added to 130 embryos at
      the 4-cell stage; to 128 embryos at the blastocyst stage; and to 147 embryos 24 h
      following spreading. Development of embryos from the 4-cell to the blastocyst
      stage, differentiation of the inner cell mass (ICM) and trophectoderm, and the
      occurrence of attachment and spreading were evaluated. Embryo development was
      significantly inhibited in cultures supplemented with 100 ng/ml EGF compared to
      the controls (P < 0.001). Development of 4-cell embryos to blastocysts occurred
      in 25% of the EGF group compared to 85% of controls. Spreading occurred in 20% of
      4-cell embryos and 30% of blastocysts treated with EGF, compared to 80 and 90% of
      corresponding controls. In embryos developing from the 4-cell stage, massive
      growth of the ICM and inhibition of the trophectoderm occurred, whereas both ICM
      and trophectoderm were inhibited by EGF in embryos developing from the blastocyst
      stage. Following spreading, EGF caused massive growth of the ICM and regression
      of the trophectoderm. Our preliminary results show that EGF may be involved in
      the modulation and control of early embryonic growth and differentiation.

PMID- 8253937
TI  - Human chorionic gonadotrophin: embryonic secretion is a time-dependent
      phenomenon.
AB  - Of 48 spare human pre-embryos achieving the expanded blastocyst stage, 22 (45.6%)
      secreted significant amounts of human chorionic gonadotrophin (HCG) (> 5
      IU/l/day). Of these, nine remained intrazonal, seven partially hatched and six
      fully hatched. Embryonic production of HCG in vitro appeared to be time
      dependent, starting after a certain minimum time (approximately 160 h post
      insemination) and rising exponentially, with maximal HCG production around day
      10. Hatching was not a prerequisite for HCG secretion, since similar amounts were
      produced by intrazonal blastocysts. Blastocysts derived from abnormally
      fertilized oocytes also began secreting HCG exponentially but secretion was
      delayed and the upper limit of maximum HCG secretion rate was comparatively low.
      The actual amount of HCG is thought to reflect the number of viable trophectoderm
      cells producing the hormone. HCG doubling times for blastocysts in vitro were
      rapid when compared to implanting blastocysts of a similar age in vivo, with
      19/22 (86.4%) blastocysts having a doubling time of < 10 h. Provided a pre-embryo
      can secrete HCG and maintain an adequate doubling time, sufficient HCG should be
      produced for initial stages of embryonic recognition in vivo. Since intrazonal
      blastocysts are capable of fulfilling both of these criteria, the limiting factor
      in realizing their full potential may be escaping from the zona pellucida.

PMID- 8253938
TI  - Temporal effects of ouabain on in-vitro development of mouse zygotes.
AB  - Ouabain is a specific inhibitor of Na(+)-K(+)-ATPase, an enzyme which controls
      the intracellular Na+ and K+ levels. In this study, in-vitro fertilized zygotes
      from a hybrid mouse strain were used to examine the temporal effects of 50 microM
      ouabain on embryonic development in vitro during the preimplantation period. A
      higher incidence of blastocyst formation at the end of the culture period was
      found when embryos were cultured in the presence of ouabain from 22 to 46 h post
      insemination, or any other period that included this time period. When zygotes
      from randomly bred mice were used, inhibition of Na(+)-K(+)-ATPase with ouabain
      clearly promoted development through the 2-cell block in vitro. As Na(+)-K(+)
      ATPase is the most important regulator of intracellular electrolyte
      concentrations in mammalian cells, these results suggest that an ionic imbalance
      exists in embryos cultured in conventional media which can be positively
      influenced by inhibiting this enzyme.

PMID- 8253939
TI  - Effects of pentoxifylline on in-vitro development of preimplantation mouse
      embryos.
AB  - In-vitro culture of 1-cell mouse embryos was used to assess the influence of
      pentoxifylline or early embryonic development. If cultured in concentrations of
      5, 10 or 50 microM, early embryonic development was unaffected and no differences
      in cell numbers were noted in embryos reaching the blastocyst stage. However, at
      3.6 and 7.2 mM, pentoxifylline inhibited cleavage from the 2-cell stage onwards.
      If 1-cell mouse embryos were exposed for only 30 min to these concentrations,
      blastocyst formation was found to be morphologically normal. However, cell
      numbers of such blastocysts were significantly decreased after exposure to
      pentoxifylline. These results may indicate that exposure of gametes or zygotes to
      pentoxifylline should be avoided as much as possible when this drug is used in
      human assisted reproduction. If administered at regular therapeutic doses, it is
      probable that no adverse effect on early embryonic development in vivo will
      occur. Further research is needed to confirm and elucidate the above findings.

PMID- 8253940
TI  - The in-vitro and in-vivo developmental potential of frozen and non-frozen
      biopsied 8-cell mouse embryos.
AB  - We investigated the in-vitro and in-vivo development of cryopreserved and non
      cryopreserved biopsied 8-cell mouse embryos, from which one to seven blastomeres
      were removed by micromanipulation. The results clearly indicate that the in-vitro
      and in-vivo development of biopsied 8-cell mouse embryos depended on the number
      of blastomeres removed: the more blastomeres removed, the greater the effect.
      When five, six, or seven blastomeres were removed, fewer blastocysts were formed.
      Furthermore, when these blastocysts were transferred to pseudopregnant females,
      no living young were formed, indicating the abnormality of these blastocysts.
      When up to three blastomeres were removed, there was no significant effect on the
      rate of in-vitro blastocyst formation. Living young were found even after the
      biopsy of four blastomeres, and after biopsy of only one or two blastomeres, the
      same percentage of living young was obtained as in the non-biopsied control
      embryos. Biopsied 8-cell mouse embryos were frozen and thawed in straws with 1,2
      propanediol (1.5 M) and sucrose (0.1 M) with slow-freezing and rapid-thawing
      protocols. The survival after cryopreservation, defined as the percentage of
      embryos with the same number of blastomeres intact as the number of blastomeres
      before freezing, was excellent and no different from non-biopsied embryos,
      independent of the number of blastomeres biopsied. Furthermore, cryopreservation
      had no further impact on the in-vitro and in-vivo development of the biopsied
      embryos.

PMID- 8253941
TI  - Oocyte donation in menopausal women.
AB  - Oocyte donation was performed by in-vitro fertilization and embryo transfer in 82
      women. The average age of the patients was 48 years (range 26-60), and 71 were
      over 40 years old, with an average follicle stimulating hormone (FSH) value of 74
      +/- 14 IU and oestradiol concentration of 30 +/- 9 pg/ml. Overall 32 clinical
      pregnancies were achieved, of which 21 reached term, three are ongoing, and eight
      were lost (six miscarriages, one abruptio placentae, and one severe gestational
      proteinuria hypertension in the second trimester). The 21 term pregnancies
      produced 26 newborns; one patient who had had three embryos replaced delivered
      triplets and three patients had twins. Before the embryo transfer was performed,
      the endometrium thickness was accurately determined by vaginal ultrasound probe.
      The highest number of implanted embryos was reached when the endometrium
      thickness was 9-12 mm.

PMID- 8253942
TI  - The effect of dose of mifepristone and gestation on the efficacy of medical
      abortion with mifepristone and misoprostol.
AB  - Although it has been demonstrated that a combination of mifepristone and a
      prostaglandin is an effective method of inducing abortion in early pregnancy, the
      optimum dose of the antigestogen is unknown. Women (n = 220) requesting abortion
      in early pregnancy (< or = 63 days amenorrhoea) were randomized to receive a
      single dose of either 600 or 200 mg mifepristone followed 48 h later by a single
      dose of 600 micrograms misoprostol by mouth. The percentage of women who had a
      complete abortion (93.6% confidence interval 90.4-95.5%) was identical in the two
      groups. There was no significant difference in the number of women who passed the
      fetus within 4 h of receiving the prostaglandin (64 versus 74%), the days of
      bleeding (14.6 +/- 1.1 versus 15.3 +/- 0.9) nor in the onset of the next period
      (39.7 +/- 1.3 versus 36.7 +/- 1.3) respectively between the groups receiving 200
      or 600 mg mifepristone. However, the complete abortion rate was significantly
      higher in women < or = 49 days compared to women 50-63 days amenorrhoea (97.5
      versus 89.1% respectively; P < 0.02). There was no difference in any of the other
      parameters at different weeks of gestation. We conclude: (i) that the recommended
      dose of mifepristone could be reduced from 600 to 200 mg without loss of clinical
      efficacy, (ii) that the combination of mifepristone and 600 micrograms
      misoprostol is a highly effective alternative to vacuum aspiration for inducing
      abortion in women < 50 days amenorrhoea and (iii) at gestation > 56 days, this
      combination may result in too many incomplete abortions to be clinically
      acceptable.

PMID- 8253943
TI  - Premature luteinization as detected by elevated serum progesterone is associated
      with a higher pregnancy rate in donor oocyte in-vitro fertilization.
AB  - Premature luteinization has been reported to be associated with decreased
      pregnancy rates in patients undergoing in-vitro fertilization. However, the
      detrimental effect created by a pre-aspiration rise in progesterone is difficult
      to assess since ovarian stimulation affects both oocyte quality and endometrial
      receptivity. Therefore, the relationship between premature luteinization and
      pregnancy rates remains uncertain. To achieve improved control for confounding
      variables, we studied premature luteinization in ovum donors of proven fertility.
      A total of 114 consecutive ovum donation cycles using pituitary suppression with
      a gonadotrophin-releasing hormone agonist followed by gonadotrophin stimulation
      were examined. Serum progesterone concentration on the day of administration of
      human chorionic gonadotrophin (HCG) was > 1.2 ng/ml in 29% of patients. Patients
      were divided into two groups based on this value. There was a significant
      increase in clinical pregnancy rates per embryo transfer in the group with higher
      progesterone concentrations (53 versus 25%, P = 0.012), as well as significantly
      more oocytes obtained at aspiration (19.6 +/- 10.4 versus 13.3 +/- 5.4, P <
      0.001), and significantly higher peak serum oestradiol values (3903 +/- 1787
      versus 2453 +/- 1232 pg/ml, P < 0.001). There were no significant differences
      between groups due to age, degree of stimulation or the number of embryos
      transferred. We conclude that premature luteinization as based on elevated serum
      progesterone concentration is a common occurrence in oocyte donors, reflects
      healthy follicular development, and is associated with increased pregnancy rates.

PMID- 8253944
TI  - Age, pregnancy and miscarriage: uterine versus ovarian factors.
AB  - This study was performed to evaluate the relative contribution of oocyte and
      uterine factors to the age-related reduction in fecundity. The pregnancy and
      miscarriage rates in women receiving donated oocytes were compared to those in
      women using their own oocytes in in-vitro fertilization (IVF) and gamete intra
      Fallopian transfer (GIFT) procedures. Oocyte donation with embryo transfer was
      performed on 241 women in 371 cycles; 116 of these women became pregnant (48% per
      patient and 31.5% per cycle) of whom 40 (35%) miscarried, giving a live birth
      rate of 20.5%. Assisted conception, in the form of IVF/GIFT procedures, was
      performed on 1331 women using their own oocytes in 2194 cycles; 627 of these
      women became pregnant (47% per patient and 28.7% per cycle), of whom 228 (36%)
      miscarried, giving a live birth rate of 18.2%. Neither the age of the donor nor
      the age of the recipient was related to pregnancy rate. The age of the donor,
      however, was directly related to the miscarriage rate. On the other hand, the age
      of patients undergoing IVF/GIFT was inversely related to the pregnancy rate and
      directly related to the miscarriage rate. In women of 40 years or over, the
      overall pregnancy and live birth rates were significantly higher and the
      miscarriage rate was significantly lower in the group receiving donated oocytes
      compared to the group using their own oocytes. In summary, we suggest that the
      age-related decline in fecundity is associated with the age of the oocytes rather
      than the age of the uterus.

PMID- 8253945
TI  - Do clinicians benefit from gamete donor anonymity?
AB  - Two groups of participants are frequently omitted from discussions and studies of
      donor anonymity in assisted conception: the children conceived and the clinicians
      providing the service. Past secrecy explains the absence of the children's views,
      but the absence of a systematic consideration of the clinician's views is more
      puzzling. Evidence from the history of donor insemination suggests that
      clinicians have supported keeping such practices secret, not just for the
      protection of donors, recipients and resultant children but also to protect their
      own position from the detailed scrutiny of others who had expressed doubts about
      the practice. However, the various important developments in both the practice
      and the regulation of assisted conception in the 1980s and the early 1990s may
      well have alleviated such earlier anxieties. None the less, a growing willingness
      by clinicians to consider greater openness in gamete donation may be counter
      balanced by the nature of their relationship with recipients, the majority of
      whom still appear to favour secrecy, and by the wider cultural uncertainty about
      the physiological and symbolic importance of genetic relationships in the
      development of the individual. It is concluded therefore that future studies of
      donor anonymity should include clinicians, in order to explore these questions in
      detail.

PMID- 8253946
TI  - British Andrology Society guidelines for the screening of semen donors for donor
      insemination.

PMID- 8253947
TI  - Variable loss of oocytes during cryopreservation.

PMID- 8253948
TI  - Development of human embryos to the hatched blastocyst stage in the presence or
      absence of a monolayer of Vero cells.
AB  - In a prospective randomized study, excess embryos from 100 women undergoing in
      vitro fertilization were cultured from the 2-cell to the hatched-blastocyst stage
      in the presence or absence of a confluent monolayer of Vero cells. The
      frequencies of fragmentation, developmental arrest, multinucleation and
      blastocyst formation were observed for 254 embryos over 7 days in culture. The
      number of nucleated cells, and fine structure of trophectoderm and inner cell
      mass were analysed at the expanded blastocyst stage on day 5.5 post-insemination.
      The frequency of hatching from the zona pellucida was determined between days 6
      and 7 post-insemination. With respect to these developmental parameters, the
      findings indicate that no overt or statistically significant improvement in early
      human embryogenesis occurs in the co-culture system.

PMID- 8253949
TI  - Use of virologic assays for detection of human immunodeficiency virus in clinical
      trials: recommendations of the AIDS Clinical Trials Group Virology Committee.

PMID- 8253950
TI  - Detection of Theileria sergenti infection in cattle by polymerase chain reaction
      amplification of parasite-specific DNA.
AB  - A pair of synthetic oligonucleotide primers, designed from the gene encoding a 32
      kDa intraerythrocytic piroplasm surface protein of Theileria sergenti, were used
      to amplify parasite DNA from the blood of T. sergenti-infected cattle by means of
      the polymerase chain reaction (PCR). PCR-amplified DNA was examined by
      electrophoresis and by dot blot or microplate hybridization using a parasite
      specific cDNA probe. PCR was specific for T. sergenti, since no amplification was
      detected with DNA from Anaplasma centrale, Babesia ovata, uninfected
      erythrocytes, and leukocytes. This method was sensitive enough to detect about
      4.5 parasites per microliters of blood with a 10-microliters sample volume.
      Moreover, of 66 specimens from grazing cattle, 40 were microscopically positive,
      whereas PCR revealed that 54 samples were positive. Therefore, PCR provides a
      useful diagnostic tool for detecting T. sergenti-infected cattle, and it is
      significantly more sensitive than the current methods.

PMID- 8253951
TI  - Polymorphism in ospC gene of Borrelia burgdorferi and immunoreactivity of OspC
      protein: implications for taxonomy and for use of OspC protein as a diagnostic
      antigen.
AB  - The nucleotide sequences of the ospC gene from five Danish human Borrelia
      burgdorferi isolates representing all three B. burgdorferi genospecies (B.
      burgdorferi sensu stricto, Borrelia garinii sp. nov., and group VS461) and from
      the American type strain B31 were determined and compared with the published ospC
      sequence from the German B. burgdorferi isolate PKo (R. Fuchs, S. Jauris, F.
      Lottspeich, V. Preac-Mursic, B. Wilske, and E. Soutschek, Mol. Microbiol. 6:503
      509, 1992). The ospC gene was present in all isolates, regardless of the presence
      or absence of its product, OspC. The deduced amino acid sequences of OspC from
      the seven isolates were aligned and revealed pairwise sequence identities ranging
      from 60.5 to 100%. Differences were scattered throughout the amino acid
      sequences. A phylogenetic tree was constructed and revealed three distinct
      phenotypic groups OspCI to OspCIII corresponding to the three delineated
      genospecies. Immunoblot analysis revealed that the seven OspC proteins tested
      have both common and specific epitopes. There is significant epitope diversity,
      since even polyclonal antisera showed serotype-restricted specificity. Therefore,
      a serodiagnostic assay for Lyme borreliosis utilizing OspC as a test antigen
      should include all three OspC phenotypes in order to obtain a species-wide
      sensitivity.

PMID- 8253952
TI  - Identification of a protein in several Borrelia species which is related to OspC
      of the Lyme disease spirochetes.
AB  - Using oligonucleotide probes which have previously been shown to be specific for
      the ospC gene found in the Lyme disease spirochete species Borrelia burgdorferi,
      B. garinii, and group VS461, we detected an ospC homolog in other Borrelia
      species including B. coriaceae, B. hermsii, B. anserina, B. turicatae, and B.
      parkeri. In contrast to the Lyme disease spirochetes, which carry the ospC gene
      on a 26-kb circular plasmid, we mapped the gene in other Borrelia species to
      linear plasmids which varied in size among the isolates tested. Some isolates
      carry multiple copies of the gene residing on linear plasmids of different sizes.
      The analyses conducted here also demonstrate that these Borrelia species contain
      a linear chromosome. Northern (RNA) blot analyses demonstrated that the gene is
      transcriptionally expressed in all species examined. High levels of
      transcriptional expression were observed in some B. hermsii isolates.
      Transcriptional start site analyses revealed that the length of the untranslated
      leader sequence was identical to that observed in the Lyme disease spirochete
      species. By Western blotting (immunoblotting) with antiserum (polyclonal) raised
      against the OspC protein of B. burgdorferi, we detected an immunoreactive protein
      of the same molecular weight as the OspC found in Lyme disease spirochete
      species. The results presented here demonstrate the presence of a protein that is
      genetically and antigenically related to OspC which is expressed in all species
      of the genus Borrelia tested.

PMID- 8253953
TI  - Use of multiple molecular subtyping techniques to investigate a Legionnaires'
      disease outbreak due to identical strains at two tourist lodges.
AB  - A multistate outbreak of Legionnaires' disease occurred among nine tour groups of
      senior citizens returning from stays at one of two lodges in a Vermont resort in
      October 1987. Interviews and serologic studies of 383 (85%) of the tour members
      revealed 17 individuals (attack rate, 4.4%) with radiologically documented
      pneumonia and laboratory evidence of legionellosis. A survey of tour groups
      staying at four nearby lodges and of Vermont-area medical facilities revealed no
      additional cases. Environmental investigation of common tour stops revealed no
      likely aerosol source of Legionella infection outside the lodges. Legionella
      pneumophila serogroup 1 was isolated from water sources at both implicated
      lodges, and the monoclonal antibody subtype matched those of the isolates from
      six patients from whom clinical isolates were obtained. The cultures reacted with
      monoclonal antibodies MAB1, MAB2, 33G2, and 144C2 to yield a 1,2,5,7 or a
      Benidorm 030E pattern. The strains were also identical by alloenzyme
      electrophoresis and DNA ribotyping techniques. The epidemiologic and laboratory
      data suggest that concurrent outbreaks occurred following exposures to the same
      L. pneumophila serogroup 1 strain at two separate lodges. Multiple molecular
      subtyping techniques can provide essential information for epidemiologic
      investigations of Legionnaires' disease.

PMID- 8253954
TI  - Cluster of Enterobacter cloacae pseudobacteremias associated with use of an agar
      slant blood culturing system.
AB  - From 1 February through 12 October 1990, 27 blood cultures processed at Shiprock
      Hospital were positive for Enterobacter cloacae; only 3 had been reported in the
      preceding 12 months. Twenty (74%) of the cultures were obtained from patients
      without clinical evidence of gram-negative septicemia. The increase in E. cloacae
      positive blood cultures was temporally associated with the introduction of a new
      blood culturing system. To evaluate potential risk factors for an E. cloacae
      positive blood culture (case-culture), we conducted a case-control study. Case
      cultures were compared with 81 randomly selected cultures that were processed
      during the epidemic period and that were not positive for E. cloacae (controls).
      Because several factors suggested the possibility of pseudoinfection, we limited
      our analysis to the 20 blood cultures that appeared to be contaminants. Blood
      samples received in the laboratory during the midnight shift (5 of 20 [25%]
      versus 5 of 81 [6%]; odds ratio, 5.1; 95% confidence intervals, 1.01 to 24.6; P =
      0.02) or present in the incubator with other E. cloacae-positive samples (17 of
      20 [85%] versus 29 of 81 [36%]; odds ratio, 10.2, 95% confidence interval, 2.6 to
      57.3; P < 0.001) were at increased risk for contamination. During mock
      experiments of the procedures for processing blood samples for culture, several
      breaks in aseptic technique and leakage from the blood culturing system were
      observed. Cultures of samples obtained from several environmental sites in the
      laboratory and the hand washings of two laboratory technicians grew E. cloacae.
      Plasmid and restriction enzyme analyses of E. cloacae isolates recovered from the
      patients' blood cultures, the two technicians' hand washings, and environmental
      sites in the laboratory indicated that all had identical plasmid profiles. Our
      findings suggest that the breaks in aseptic technique and the environmental
      contamination that occurred in association with the use of the new blood
      culturing system resulted in contamination of the blood cultures. This outbreak
      highlights the importance of routine environmental cleaning, periodic quality
      control assessments, and adherence to aseptic practices in clinical laboratories,
      particularly when new methods or equipment are introduced and/or new personnel
      are hired.

PMID- 8253955
TI  - Expression of A and B subunits of Shiga-like toxin II as fusions with glutathione
      S-transferase and their potential for use in seroepidemiology.
AB  - We used the plasmid vector pGEX-2T for the expression of recombinant subunits of
      Shiga-like toxin II (SLT-II). The 5' terminus of the genes that code for either
      the SLT-IIA or SLT-IIB subunits was genetically fused to the 3' terminus of the
      gene coding for the enzyme glutathione S-transferase, which serves as a carrier
      in this expression system. The subunit genes were constructed synthetically by
      polymerase chain reaction, with appropriate restriction sites to permit in-frame
      downstream insertion of the genes. The resulting plasmids containing the A and B
      subunit genes were designated pFG1 and pFG2, respectively. Induction of
      Escherichia coli laboratory strains harboring pFG1 with isopropyl-beta-D
      thiogalactopyranoside (IPTG) yielding only small quantities of SLT-IIA fusion
      proteins. Since IPTG induction was lethal for cells harboring pFG2, we
      constructed the recombinant plasmid pFG4, which contained a subgenic fragment of
      slt-IIB but without the 5' signal sequence. With this construct we were able to
      express very large quantities of a 33.5-kDa fusion protein, which was purified by
      affinity chromatography on immobilized glutathione and used as an antigen in
      immunoblot analysis. Rabbit serum against native SLT-II, as well as all of 12
      serum samples with high neutralizing activity against SLT-II, reacted with SLT
      IIB purified from an E. coli pFG4 expression system, whereas only 3 of 208 human
      serum samples with low neutralization titers and none of 54 serum samples with no
      SLT-II-neutralizing capability reacted. Failure of specific reactivity with the
      SLT-IIB fusion protein in the majority of human serum samples with low
      neutralizing activity suggests that serum factors other than immunoglobulins may
      be responsible for neutralizing activity in these cases. The immunoblot assay
      with recombinant SLT-IIB as the antigen can be recommended for use in a
      diagnostic setting as a simple and reliable approach to detect specific human
      serum antibodies to SLT-II.

PMID- 8253956
TI  - Enhanced detection of intracellular organism of swine proliferative enteritis,
      ileal symbiont intracellularis, in feces by polymerase chain reaction.
AB  - A sensitive assay based on amplification of a 319-bp DNA fragment of the
      intracellular bacterium of swine proliferative enteritis was developed for the
      detection of the organism in the feces of swine. A vernacular name, ileal
      symbiont intracellularis (IS-intracellularis), has recently been published for
      the intracellular bacterium, which was formerly known as a Campylobacter-like
      organism (C.J. Gebhart, S.M. Barnes, S. McOrist, G.F. Lin, and G.H.K. Larson,
      Int. J. Syst. Bacteriol. 43:533-538, 1993). As few as 10(1) IS-intracellularis
      organisms purified from intestinal mucosa, or 10(3) IS-intracellularis per g of
      feces, were detected. No amplification product was produced from a polymerase
      chain reaction performed on DNA extracted from the feces of healthy pigs. A 319
      bp DNA fragment specific for IS-intracellularis was produced on amplification of
      DNA from the feces of pigs with experimental and naturally occurring
      proliferative enteritis.

PMID- 8253957
TI  - Molecular analysis of multiple isolates of the major serotypes of group B
      streptococci.
AB  - Serotyping of clinical isolates is a widely used technique for epidemiologic
      study of group B streptococcal infections. However, serotyping cannot
      definitively determine epidemiologically related or unrelated isolates. We
      investigated the use of restriction endonuclease analysis (REA) with both
      conventional agarose gel electrophoresis (AGE) and pulsed-field gel
      electrophoresis (PFGE) in 50 isolates of the major serotypes of group B
      streptococci. Single digestion with HindIII and HaeIII and double digestion with
      HindIII and then EcoRI were used for conventional AGE, and digestion with SmaI
      was used for PFGE. The molecular profile of one strain was compared with those of
      the strains within the same serotype as well as with the profiles from strains of
      different serotypes. Among 10 type Ia, Ia/alpha, Ia/alpha+beta, and Ia/R1
      isolates and depending on the restriction enzyme used, we found between five and
      six REA patterns by conventional AGE and seven by PFGE; among 4 type
      Ib/alpha+beta isolates we found 2 to 4 REA patterns by conventional AGE and 4 by
      PFGE; among 21 type II, II/alpha, II/beta, II/alpha+beta, and II/R4 isolates, we
      found 11 REA patterns by both AGE and PFGE; and among 14 type III, III/R1, and
      III/R4 isolates, we found from 7 to 12 different REA patterns by AGE and 10 by
      PFGE. In total, among 13 serotypes and one nontypeable strain, we found 29 to 31
      REA patterns by conventional AGE and 33 by PFGE. A particular REA pattern within
      a serotype was different from the patterns found in the other serotypes,
      suggesting that REA analysis by using conventional AGE or PFGE is a sensitive
      method for analyzing genetic relatedness and diversity in group B streptococci
      and has potential value in molecular epidemiologic studies.

PMID- 8253958
TI  - Comparison of commercial diagnostic tests for Helicobacter pylori antibodies.
AB  - A number of serological tests measuring the presence of Helicobacter pylori
      specific serum immunoglobulin G (IgG) are now commercially available. The aim of
      this study was to evaluate the clinical accuracy of five commercial H. pylori
      antibody tests: GAP-IgG (Biomerica), HELpTEST (AMRAD, Kew, Victoria, Australia),
      HELICO-G (Porton Cambridge), Pyloriset (Orion Diagnostica), and ROCHE (Roche
      Diagnostics). A total of 162 subjects presenting for routine upper endoscopy were
      studied. H. pylori was diagnosed if culture, histology, or both were positive.
      Ten milliliters of venous blood was collected at the time of endoscopy for
      serological assessment. The sensitivity and specificity of each test (GAP-IgG,
      HELpTEST, HELICO-G, Pyloriset, and ROCHE) were as follows: 83 and 79%, 92 and
      77%, 86 and 65%, 89 and 56%, and 98 and 69%, respectively. Positive and negative
      predictive values were 97 and 83%, 90 and 91%, 76 and 83%, 68 and 84%, and 86 and
      97%, respectively. The specificity of most tests increased by approximately 10%
      when sera from subjects less than 45 years old were examined. The number of sera
      falling into the grey zone for each test (an indeterminate result with respect to
      H. pylori status) varied between 2.5 and 19%. This study highlights the need for
      all serological kits to be independently evaluated on the population to be
      studied by testing against a microbiologically defined panel of H. pylori
      positive and -negative sera.

PMID- 8253959
TI  - Quantitation of enteroviral RNA by competitive polymerase chain reaction.
AB  - The polymerase chain reaction (PCR) is a new diagnostic technique for the
      detection of enteroviral infection; however, it currently provides only
      qualitative results. The aim of this study was to adapt PCR for the accurate
      quantitation of enteroviral RNA in clinical specimens. For this purpose, we
      designed a standard RNA which was homologous to sequences at the 5' end of the
      coxsackie B3 enterovirus genome but contained a single-base-pair mutation which
      created a novel internal restriction site. Serial dilutions of this standard
      template RNA were mixed with a fixed concentration of coxsackie B3 enterovirus
      RNA. The viral and standard templates were reversed transcribed to cDNA and
      coamplified by PCR, and a comparison of the radioactive PCR products was made.
      Since the templates were both present in a single reaction tube and competed for
      the same primers, the ratio of products remained proportional throughout the
      amplification process. By this approach, a fourfold-difference in viral titer was
      clearly distinguishable. Moreover, we were able to accurately quantitate as few
      as 15 50% tissue culture infectious doses, which reflects common clinical viral
      titers. This study lays the foundation for quantitation of enteroviral RNA in
      clinical specimens and establishes a technique that can readily be applied to the
      diagnosis of enteroviral infection.

PMID- 8253960
TI  - Clinical evaluation of a new polymerase chain reaction assay for detection of
      Chlamydia trachomatis in endocervical specimens.
AB  - A clinical evaluation of the Amplicor polymerase chain reaction (PCR) assay for
      the detection of Chlamydia trachomatis in endocervical swabs (Roche Molecular
      Systems, Branchburg, N.J.) is described. This new clinical system used one-step
      sample preparation, amplification with biotinylated cryptic plasmid primer pairs
      (CP24-CP27), uracil-N-glycosylase (AmpErase), and a microtiter format for
      amplicon capture and detection. Culture with McCoy cells in duplicate 1-dram
      (3.697-ml) vials with fluorescent immunostaining was the reference system.
      Endocervical swab samples from 945 women provided 74 culture-positive specimens,
      of which PCR detected 71. The initial PCR result was positive for 12 additional
      specimens. Arbitration of the PCR-positive, culture-negative samples by PCR with
      major outer membrane protein primers, duplicate culture, elementary body direct
      fluorescent-antibody staining, and DNA extraction PCR showed that all 12 samples
      were positive for chlamydia, raising the number of truly positive samples from 74
      to 86. After arbitration the true sensitivities of PCR and culture were 96.5 and
      86%, respectively (P = 0.02). Specificities for both were 100%. For PCR, the
      positive and negative predictive values were 100 and 99.7%, respectively. Total
      test efficiency was 99.7%. A high-test-volume (121 samples) timing study with all
      items included in the College of American Pathologists work load method indicated
      that this PCR format took approximately 3 min per sample. Because of the high
      sensitivity, specificity, and improved ease of handling, we found PCR to be a
      good alternative to culture for detection of C. trachomatis.

PMID- 8253961
TI  - Improved purification and biologic activities of staphylococcal toxic shock
      syndrome toxin 1.
AB  - An improved method for producing highly purified toxic shock syndrome toxin 1
      (TSST-1) by preparative isoelectric focusing in a Bio-Rad Rotofor cell and then
      chromatofocusing is described. Purification to homogeneity was confirmed by
      silver staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE; 50 micrograms of protein was loaded), by immunoblotting with
      polyclonal rabbit antiserum raised against the crude culture supernatant used for
      purification, and by autoradiography after iodination and SDS-PAGE. Biologic
      activity was demonstrated by mitogenicity and cytokine induction (tumor necrosis
      factor alpha [TNF-alpha], interleukin 1-beta [IL-1 beta], and IL-6) of human
      peripheral blood mononuclear cells (PBMCs) and by lethality in New Zealand White
      rabbits following subcutaneous infusion. In contrast to commercial TSST-1
      preparations, our TSST-1 preparation required the presence of both monocytes and
      T cells for the induction of TNF-alpha and IL-1 beta from human PBMCs. A 46-kDa
      contaminating protein in the commercial TSST-1 preparation, identified as
      staphylococcal lipase, was likely responsible for the induction of TNF-alpha and
      IL-1 beta from human monocytes in the absence of T cells, a biologic activity
      falsely attributed to purified TSST-1. Our improved purification procedure for
      TSST-1 provides a high yield and is both more rapid and less labor intensive than
      previously reported methods. Furthermore, our studies clearly demonstrate the
      need for stringent methods of purity assessment of TSST-1 preparations before
      ascribing to them their potent biologic activities.

PMID- 8253962
TI  - Evaluation of polymerase chain reaction for diagnosis of pneumococcal pneumonia.
AB  - To test the ability of the polymerase chain reaction (PCR) to detect
      Streptococcus pneumoniae in blood, we generated two sets of nested primers. The
      first defined 559-bp and 649-bp regions of the pneumolysin gene, and the second
      defined 445-bp and 553-bp regions of the autolysin gene. These nucleotide
      segments were detected in DNAs from isolates of all 20 pneumococcal serotypes
      tested, but they were not detected when used to test DNAs from 41 isolates of
      nonpneumococcal bacteria and fungi. The sensitivity was evaluated by using
      purified pneumococcal DNA. We were able to detect 10 fg of S. pneumoniae DNA, or
      4.3 genome equivalents. Blood samples were obtained from 16 patients with culture
      proven pneumococcal bacteremia and were subjected to PCR analysis. Of eight buffy
      coat fractions tested, six showed reactivity in the PCR with the pneumolysin
      primers, and five of the eight produced the expected products when tested with
      the autolysin primers (sensitivities, 75 and 63%, respectively). Of the eight
      whole-blood specimens tested, only three produced the expected products with
      either set of primers. Additionally, we tested 14 samples from patients with
      bacteremia that were culture positive for nonpneumococcal bacterial species, and
      13 were negative (specificity, 93%). This combination of sensitivity and
      specificity may make detection of S. pneumoniae in blood by PCR in comparison
      with that by blood culture a very promising alternative for a means of definitive
      diagnosis.

PMID- 8253963
TI  - Analysis of human papillomavirus types in exophytic condylomata acuminata by
      hybrid capture and Southern blot techniques.
AB  - Exophytic condylomata acuminata of the external genitalia of 40 patients were
      analyzed for human papillomavirus (HPV) DNA by the Southern blot and hybrid
      capture methods. All lesions were initially analyzed by the Southern blot method
      by using a mixture of HPV type 6, 11, 16, and 18 whole genomic probes. Southern
      blots demonstrated characteristic PstI restriction patterns of HPV type 6, 11, or
      16 in all but one lesion. HPV 6 subtypes accounted for 28 of 39 HPV-positive
      lesions. Twenty-seven of these 28 lesions contained HPV type 6a, and 1 lesion
      contained HPV type 6c. Eight lesions contained HPV type 11 and three contained
      HPV type 16. Two of the three condylomata acuminata containing HPV type 16 were
      obtained from solid-organ transplant recipients receiving immunosuppressive
      medications. The third lesion containing HPV type 16 was a typical exophytic
      condyloma acuminatum from a woman with previously resected vulvar carcinoma. The
      hybrid capture assay detected HPV DNAs in all lesions except the Southern blot
      negative lesion. Twenty-five lesions were positive for the A probe only (HPV
      types 6 and 11 and related types). All of these lesions were found to contain HPV
      type 6 or 11 sequences in the Southern blot assay. The remaining 14 lesions were
      positive for both the A probe and the B probe (HPV types 16 and 18 and related
      types). The strongest signal in these 14 lesions by the hybrid capture assay was
      consistent with the result of the Southern blot assay in all but one case. We
      conclude that (i) HPV type 6a is the most common type found in these lesions,
      (ii) HPV type 16 may be present more often in exophytic condylomata acuminata
      from immunosuppressed individuals, (iii) hybrid capture is a useful tool for
      documenting the presence of HPV sequences in DNAs from exophytic condylomata
      acuminata, and (iv) in samples containing multiple HPV types, hybrid capture
      allows detection of minority HPV types.

PMID- 8253964
TI  - Prevalence of bacterial respiratory pathogens in the nasopharynx in breast-fed
      versus formula-fed infants.
AB  - In several studies, breast-feeding has been associated with decreased frequency
      or duration of otitis media episodes. If a causal relationship exists, the
      mechanism of protection of breast-feeding has not been established. We
      hypothesized that infants who are breast-fed, compared with infants who are
      formula-fed, have a lower prevalence of nasopharyngeal colonization with the
      bacterial respiratory pathogens (Streptococcus pneumoniae, Haemophilus
      influenzae, Moraxella catarrhalis, Streptococcus pyogenes) commonly isolated from
      the middle ear effusions of children with acute otitis media. In two private
      pediatric practices, we obtained specimens from the nasopharynx for culture from
      211 infants at 1 month of age and from 173 of these infants at 2 months of age. A
      swab was left in place in the nasopharynx for 45 s and was then immediately
      transferred onto appropriate culture media. Exclusively breast-fed (n = 84) and
      exclusively formula-fed (n = 76) infants were similar regarding the number of
      persons in the household, the number of children in the household, the number of
      siblings in day care, and the proportion with a recent upper respiratory tract
      infection. The two groups did not differ significantly in the proportions found
      to have one or more respiratory pathogens at 1 month of age (10.7 versus 18.4%; P
      = 0.12) or 2 months of age (34.8 versus 35.1%; P = 0.57). We conclude that during
      the first 2 months after birth, the exclusive receipt of breast milk appears not
      to substantially influence the prevalence of nasopharyngeal colonization with
      common bacterial respiratory pathogens.

PMID- 8253965
TI  - Quantitative evaluation of hepatitis C virus RNA in patients with concurrent
      human immunodeficiency virus infections.
AB  - Quantitation of the hepatitis C virus (HCV) provides a powerful epidemiologic and
      therapeutic method for the evaluation of infected patients. In this study
      semiquantitative reverse transcriptase polymerase chain reaction (PCR) is
      compared with a new branched DNA signal amplification methodology. Samples from
      HCV-infected patients as well as from human immunodeficiency virus-infected
      patients were evaluated. Reverse transcriptase PCR correlated well with the
      branched DNA assay (r = 0.7036, P < 0.05). HCV RNA was found to occur at
      significantly higher titers (P < 0.05) in patients coinfected with the human
      immunodeficiency virus compared with titers in those infected with HCV alone.
      Immune status as defined by the CD4+ count was not associated with the observed
      difference in viral titer.

PMID- 8253966
TI  - Two percent sodium chloride is required for susceptibility testing of
      staphylococci with oxacillin when using agar-based dilution methods.
AB  - The need to add NaCl to agar media to ensure accuracy of results when testing
      staphylococci with oxacillin was investigated. The results of four antimicrobial
      susceptibility testing methods (agar and broth dilution, E test, and disk
      diffusion) in which the growth medium contained 0, 2, 4, or 5% NaCl were compared
      with the results of a hybridization assay using a mec gene probe. We tested 223
      strains of staphylococci, 128 of which were mec gene positive. A total of 7 of
      the 128 positive strains were coagulase-negative staphylococci with 24-h
      oxacillin MICs of < or = 2 micrograms/ml. Ninety-five isolates were mec gene
      negative, including seven strains of Staphylococcus aureus with oxacillin MICs of
      > or = 4 micrograms/ml. The oxacillin MICs for mec gene-positive, oxacillin
      resistant strains of staphylococci increased two- to fourfold with the addition
      of NaCl to the test medium, while the MICs for mec gene-negative strains did not
      change in the presence of added salt. Very major error rates for the agar
      dilution and E test methods in the absence of salt ranged from 18.2 to 20.2%.
      Major error rates for mec gene-negative S. aureus isolates were > 17% for all
      test methods when 4 or 5% NaCl was added to the test medium. The addition of 2%
      NaCl to Mueller-Hinton agar for testing of oxacillin resulted in very major error
      rates of < 1% for the agar dilution and E test methods although the major error
      rates for the two methods with added NaCl were 8.5 and 6.9%, respectively. The
      disk diffusion test did not perform well in this study, showing essential error
      rates of > or = 18.3%. We recommended the addition of 2% NaC1 to Mueller-Hinton
      agar when testing staphylococci with oxacillin by either the agar dilution or E
      test method. NaC1 should not be added for the disk diffusion test.

PMID- 8253967
TI  - Comparison of the Septi-Chek AFB and BACTEC systems and conventional culture for
      recovery of mycobacteria.
AB  - The performance of the Septi-Chek AFB system was compared with that of the BACTEC
      radiometric system and that of Lowenstein-Jensen agar slants (LJ) for detection
      of mycobacteria in clinical specimens. A total of 642 specimens were cultured; 61
      (9.5%) yielded mycobacteria. Mycobacterium tuberculosis (34 isolates) and
      Mycobacterium avium complex (25 isolates) were the predominant species isolated.
      Of the 61 culture-positive specimens, 30 were smear positive and 31 were smear
      negative. Overall, 95% of the positive specimens were detected by Septi-Chek and
      BACTEC (100% of M. tuberculosis isolates) and 75% by LJ (82% of M. tuberculosis
      isolates). The mean times to detection were 15 days for BACTEC, 23 days for Septi
      Chek, and 27 days for LJ. Of the 30 smear-positive specimens, 100% were recovered
      by Septi-Chek and BACTEC and 90% were recovered by LJ. Of the 31 smear-negative
      specimens, 90% were detected by Septi-Chek and BACTEC and 61% were detected by
      LJ. The Septi-Chek and BACTEC systems are superior to the conventional (LJ)
      mycobacterial culture method. Although Septi-Chek requires more time for the
      detection of mycobacteria than BACTEC, it is comparable in terms of overall
      recovery.

PMID- 8253968
TI  - DNA large restriction fragment patterns of sporadic and epidemic nosocomial
      strains of Mycobacterium chelonae and Mycobacterium abscessus.
AB  - Large restriction fragment (LRF) pattern analysis of genomic DNA using pulsed
      field gel electrophoresis was performed on three reference strains, 32 sporadic
      isolates, and 92 nosocomial isolates from 12 epidemics of Mycobacterium chelonae
      and Mycobacterium abscessus. Only 17 of 30 (57%) unrelated strains of M.
      abscessus, compared with 10 of 11 (91%) of M. chelonae strains, gave satisfactory
      DNA extractions, with the remainder resulting in highly fragmented DNA. DraI,
      AsnI, XbaI, and SpeI gave satisfactory LRF patterns. Sporadic isolates of the two
      species had highly variable LRF patterns, except for one reference strain and one
      sporadic isolate of M. chelonae that differed by only two to five bands.
      Evaluation of repeat isolates from five patients monitored for 8 months to 13
      years (mean, 5.8 years) revealed LRF patterns to be stable, with changes of not
      more than two bands. LRF analysis of the seven nosocomial outbreaks with
      evaluable DNA revealed identical patterns in most or all of the patient isolates
      and in three outbreaks revealed identity with environmental isolates. These
      outbreaks included endoscope contamination, postinjection abscesses, and surgical
      wound infections. LRF analysis of genomic DNA is a useful technique for
      epidemiologic studies of M. abscessus and M. chelonae, although improved
      technology is needed for the approximately 50% of strains of M. abscessus with
      unsatisfactory DNA extractions.

PMID- 8253970
TI  - Evidence of an epidemic of Blastocystis hominis infections in preschool children
      in northern Jordan.
AB  - Blastocystis hominis is now gaining acceptance as an agent of human intestinal
      disease. A case-control study of the cause of gastroenteritis in children less
      than 6 years old was conducted. A total of 500 stool specimens were examined by
      wet mount preparation, formalin-ether concentration, Sheather's sugar flotation
      technique, and permanent stains when necessary. B. hominis was found in 63 (25%)
      of 250 stool specimens of the cases examined; 38 (15%) of these specimens
      contained this parasite alone. The appearance of severe symptoms was associated
      with increased numbers of the parasite in the diarrheic specimens (more than five
      parasites per field at a magnification of x 400). The most common symptoms were
      abdominal pain, recurrent diarrhea, cramps, anorexia, and fatigue. Contaminated
      water was suspected to be the major source of infection, since several cases were
      associated with Giardia infection. These findings support the concept of B.
      hominis pathogenicity in children with gastroenteritis.

PMID- 8253969
TI  - Evaluation of chlamydiazyme enzyme immunoassay for detection of Chlamydia
      trachomatis in urine specimens from men.
AB  - Paired first-voided urine and urethral swab specimens were collected from 540 men
      attending sexually transmitted disease clinics in three geographic locations.
      Urine specimens were tested for the presence of Chlamydia trachomatis by
      commercial enzyme immunoassay (Chlamydiazyme), and the results were compared with
      those of urethral swab cultures. Overall prevalence of urethral C. trachomatis by
      culture was 14%, and the Chlamydiazyme assay had an overall sensitivity of 83%, a
      specificity of 96%, a positive predictive value of 76%, and a negative predictive
      value of 97%. Sensitivity was greater (94%) in those culture-positive samples
      with a high antigen load (> or = 20 inclusion-forming units per coverslip) than
      those with a lower antigen load (68%). Assay of urine specimens from men
      attending sexually transmitted disease clinics by Chlamydiazyme appears to be a
      reliable, noninvasive method of detection of C. trachomatis infection, and
      further evaluation of its performance in asymptomatic and low-prevalence
      populations is indicated.

PMID- 8253971
TI  - Immunomagnetic purification to facilitate DNA diagnosis of Plasmodium falciparum.
AB  - The detection of pathogens by polymerase chain reaction (PCR) in clinical
      samples, such as blood, urine, or feces, requires initial sample preparation to
      remove polymerase inhibitors and to concentrate the target DNA. Here we show for
      the first time that immunomagnetic separation can be used to recover pathogens
      from whole blood and then used for PCR analysis. With antibodies to the merozoite
      surface protein (MSP1), the malaria-causing parasite Plasmodium falciparum was
      purified and concentrated from clinical samples. The recovered parasites were
      used directly for in vitro DNA amplification. The PCR product was subsequently
      analyzed by a colorimetric 96-well microtiter plate assay. The results from
      examining 117 patients attending a clinic in the Borai district, Thailand,
      demonstrate that the combined method with immunomagnetic separation followed by
      PCR increases the group of positively diagnosed patients compared with
      microscopic examination of stained blood films. Analysis of 1 microliter of whole
      blood resulted in a 12% (14 of 117) increase in positively diagnosed patients
      while a 10-microliters sample volume increased the positives diagnosed to 20.5%
      (24 of 117).

PMID- 8253972
TI  - Polymerase chain reaction assay for diagnosis of potentially toxinogenic
      Corynebacterium diphtheriae strains: correlation with ADP-ribosylation activity
      assay.
AB  - We have developed a polymerase chain reaction assay for the clinical diagnosis of
      potentially toxinogenic strains of Corynebacterium diphtheriae, the causative
      agent of diphtheria. A 910-bp amplification product, overlapping a DNA portion
      encoding both fragments of the diphtheria toxin, has been found in 28 among the
      36 strains tested. In addition, effective toxin production, as evidenced by the
      ability of bacterial culture supernatants to ADP ribosylate eukaryotic elongation
      factor 2, was determined. In every case, the presence of an amplification product
      correlated with an ADP-ribosylation activity, thus confirming the diagnosis. The
      polymerase chain reaction assay herein described is very rapid (2 h) compared
      with the Elek immunodiffusion test or the guinea pig lethality test. It can
      provide a convenient and reliable method for laboratories involved in the
      identification of toxinogenic corynebacteria.

PMID- 8253973
TI  - DNA fingerprinting of Streptococcus pneumoniae strains by pulsed-field gel
      electrophoresis.
AB  - Pulsed-field gel electrophoresis of genomic DNA was carried out on Streptococcus
      pneumoniae strains to determine its value in the epidemiological survey of
      pneumococcal infections. Twenty-one clinical strains were chosen to cover a broad
      range of diversity according to geographic location, penicillin susceptibility,
      serotype, and multilocus enzyme electrophoresis (MLEE) pattern. The restriction
      endonucleases ApaI and SmaI were used to digest intact chromosomes, and the
      fragments were resolved by field inversion gel electrophoresis (FIGE). Each
      digest produced 10 to 19 fragments for comparison between strains. All the
      strains, including strains of the same serotype and strains with the same MLEE
      profile, had different FIGE patterns. In some cases, the restriction patterns
      differed by only a few fragment bands, and two isolates differed only in the
      location of a single DNA fragment. The polymorphism obtained with FIGE was
      greater than those obtained with serotyping and MLEE analysis. The stability of
      the FIGE profiles was established by testing of two independent clones derived
      from pneumococcus strain R36A. These results indicated that pulsed-field gel
      electrophoresis should be an effective tool for the typing of S. pneumoniae
      strains, capable of subdividing serotypes or MLEE types and of tracing the origin
      of pneumococcal strains.

PMID- 8253974
TI  - An immunoblotting diagnostic assay for heartwater based on the immunodominant 32
      kilodalton protein of Cowdria ruminantium detects false positives in field sera.
AB  - Heartwater, a major constraint to improved livestock production in Zimbabwe,
      threatens to invade areas which have been previously unaffected. To monitor its
      spread in Zimbabwe, an immunoblotting diagnostic assay based on the responses of
      animals to the immunodominant, conserved 32-kDa protein of Cowdria ruminantium
      was evaluated. In this assay, no false reactions were detected with sera known to
      be positive and negative, but sera from some cattle, sheep, and goats from
      heartwater-free areas of Zimbabwe reacted strongly with the 32-kDa protein,
      suggesting that either these animals had previous exposure to heartwater or they
      were false positives. To investigate the possibility of previous exposure to
      heartwater, 11 immunoblot-positive and 6 immunoblot-negative sheep from
      heartwater-free areas of Zimbabwe were compared regarding their susceptibilities
      to challenge with C. ruminantium. Prior to challenge, C. ruminantium could not be
      detected in any sheep by transmission to Amblyomma hebraeum ticks or by the
      polymerase chain reaction (PCR) conducted with plasma samples. All sheep were
      equally susceptible to the challenge, and infection was confirmed by brain
      biopsy, necropsy, PCR, and transmission of C. ruminantium to ticks. Our data
      suggest that the immunoblot-positive reactions of sera from heartwater-free areas
      were due not to previous C. ruminantium infection but rather to antigenic cross
      reactivity between C. ruminantium and another agent(s) such as Ehrlichia species.
      In conclusion, the immunodominant 32-kDa protein is not antigenically specific to
      C. ruminantium and its use in serological diagnosis of heartwater requires
      reevaluation.

PMID- 8253975
TI  - Enzyme-linked immunosorbent assay reactivity of torovirus-like particles in fecal
      specimens from humans with diarrhea.
AB  - Toroviruses are recognized enteric pathogens of cattle and horses; in humans,
      similar pleomorphic particles have been described, but doubt has been raised
      concerning their identity as viruses. We screened fecal samples from humans with
      diarrhea for the presence of torovirus-like particles (TVLPs) by electron
      microscopy and subsequently used an enzyme-linked immunosorbent assay (ELISA)
      with bovine torovirus reference reagents to test for the presence of torovirus
      antigens. To add another selection criterion to this heterologous ELISA, we
      enriched the TVLPs from the stool specimens by using sucrose density gradients
      before testing. The results of ELISA and EM correlated significantly, the ELISA
      having a sensitivity of 68% and a specificity of 86% (chi-square, P < 0.0001). In
      the gradient, peaks of ELISA reactivity were found at a buoyant density of 1.16
      g/ml and were parallel to those found when using bovine torovirus. Furthermore,
      in 50% of the ELISA-positive gradients, a hemagglutinin for human group O
      erythrocytes comigrated with the peaks of ELISA reactivity. We were unable to
      isolate human TVLPs in human colonic tumor or rectal tumor cells. We cloned and
      sequenced amplification products obtained by low-stringency polymerase chain
      reaction amplification using consensus primers mapping to the 3' end of the
      genome of animal toroviruses, but found no significant homologies with animals
      torovirus sequences. Rabbits were inoculated with material from the gradient peak
      fractions of human stool specimens, and their sera were assayed for immunologic
      comparison with bovine torovirus as a reference. A two-way antigenic cross
      reactivity was seen between human TVLP and bovine torovirus reagents when tested
      by ELISA. The rabbit antisera to human TVLP detected a higher number of electron
      microscopy-positive stool specimens than did the rabbit antisera to bovine
      torovirus. The application of these assays and reagents should help to elucidate
      the roles of TVLPs and toroviruses in diarrheal disease in humans.

PMID- 8253976
TI  - Comparison of polymerase chain reaction, culture, and western immunoblot serology
      for diagnosis of Bordetella pertussis infection.
AB  - Polymerase chain reaction (PCR) amplification of the pertussis toxin promoter
      region was used to detect Bordetella pertussis infection in nasopharyngeal
      aspirates collected from 24 infants and children infected with pertussis and 13
      adult contacts during an epidemiological study. The sensitivity of this PCR assay
      was approximately one bacterium, and the assay was specific for B. pertussis in
      tests with other Bordetella species and other respiratory pathogens. The
      pertussis case definition required a cough with a duration of more than 21 days
      for infants and children and laboratory confirmation by serology as the primary
      detection method for infants, children, and adults. The sensitivity of PCR and
      culture on Bordet-Gengou agar medium was assessed with regard to the case
      definitions. In the group of infants and children (index cases), the
      sensitivities of the culture and the PCR were 54.1% (13 of 24) and 95.8% (23 of
      24), respectively. In the adult group (household contacts), the sensitivities of
      the two methods were 15.4% (2 of 13) and 61.5% (8 of 13), respectively. PCR
      combined with pertussis-specific serology appears to be a useful tool for
      diagnosis of pertussis especially in epidemiological studies.

PMID- 8253978
TI  - Growth of 28 Legionella species on selective culture media: a comparative study.
AB  - We compared the growth of 28 Legionella spp. on four manufacturers' buffered
      charcoal-yeast extract (BCYE) agar media and selective BCYE media that contained
      polymyxin B, anisomycin, and vancomycin or cefamandole. With BCYE as a "gold
      standard," growth for Legionella pneumophila was significantly better than for
      the nonpneumophila species on all media tested. L. pneumophila and 24 other
      Legionella spp. grew on vancomycin-containing media, while L. santicrucis, L.
      rubrilucens, and L. erythra grew poorly. In contrast, 11 of 28 species (notably
      L. micdadei and L. bozemanii) did not grow on cefamandole-containing media and 8
      of 28 species only grew marginally. We demonstrated that selective BCYE media
      that contain vancomycin or cefamandole may not support the growth of all
      Legionella spp. One commercial manufacturer's media were consistently suboptimal.
      Laboratories should not rely on a manufacturer's quality control testing in lieu
      of their own.

PMID- 8253977
TI  - Use of monoclonal antibodies to distinguish pathogenic Naegleria fowleri (cysts,
      trophozoites, or flagellate forms) from other Naegleria species.
AB  - Monoclonal antibodies (MAbs) reactive to the pathogenic amoeba Naegleria fowleri
      were analyzed by enzyme-linked immunosorbent assay (ELISA), indirect
      immunofluorescence assay, Western blotting (immunoblotting), and
      radioimmunoprecipitation assay (RIPA). Two MAbs (3A4 and 5D12) showed reactivity
      by ELISA with all N. fowleri strains tested and no reactivity with the five other
      Naegleria species, N. lovaniensis, N. gruberi, N. australiensis, N. jadini, and
      N. andersoni. These MAbs reacted with the three morphological forms of N. fowleri
      (trophozoites, cysts, and flagellates). The reactivity on Western blots was
      suppressed by treatment with metaperiodate, suggesting a carbohydrate epitope.
      Differences in reactivity patterns between trophozoites and cysts observed with
      radioimmunoprecipitation assay might reflect differences in biological
      properties. The formalin stability of the epitope may be useful in detecting N.
      fowleri in fixed biopsies and in investigating the pathological process.

PMID- 8253979
TI  - Isolation of a DNA probe for identification of Mycobacterium kansasii, including
      the genetic subgroup.
AB  - In order to develop a DNA-based assay to identify all Mycobacterium kansasii
      clinical isolates, a specific DNA probe was isolated in plasmid p6123. A total of
      145 M. kansasii clinical isolates were collected from several countries and were
      examined with three probes by DNA hybridization. Of the 145 isolates, 115 (79%)
      were positive with the previously described probe pMK1-9 (Z. H. Huang, B. C.
      Ross, and B. Dwyer, J. Clin. Microbiol. 29:2125-2129, 1991), 129 (88%) were
      positive with the commercial Accu-probe assay (Gen-Probe), and 145 (100%) were
      positive with the p6123 probe. Southern blot analysis of EcoRI-digested M.
      kansasii chromosomal DNA with p6123 revealed that all Accu-probe-positive M.
      kansasii strains exhibited a 3-kb fragment, whereas all Accu-probe-negative M.
      kansasii strains displayed DNA fragments of variable molecular sizes. These
      results indicate that, unlike the previously described probes for M. kansasii,
      the fragment cloned into p6123 identified all 145 biochemically typical strains
      tested and provides an ideal target for future DNA-based speciation assays.

PMID- 8253980
TI  - Differentiation of strains of Actinobacillus actinomycetemcomitans by arbitrarily
      primed polymerase chain reaction.
AB  - The present study describes a method for amplifying DNA in Actinobacillus
      actinomycetemcomitans by using short, synthetic oligonucleotides of random
      sequence as primers in the polymerase chain reaction. Genomic DNA from each of 20
      human isolates of A. actinomycetemcomitans was successfully amplified in a
      thermal cycler with a single synthetic primer (GGGTAACGCC) and reproducibly
      produced 14 different DNA amplification profiles (amplitypes). A.
      actinomycetemcomitans isolates from the same subject revealed the same amplitype.
      The arbitrarily primed polymerase chain reaction appears to be useful in
      characterizing human isolates of A. actinomycetemcomitans for studies of
      epidemiology and bacterial transmission.

PMID- 8253981
TI  - Identification and characterization of multiple species of vancomycin-resistant
      enterococci, including an evaluation of Vitek software version 7.1.
AB  - A total of 374 clinical isolates of Enterococcus spp. were characterized to
      determine the species distribution and vancomycin resistance. The ability of the
      Vitek system (bioMerieux Inc, Hazelwood, St. Louis, Mo.) to identify enterococci
      to the species level and to recognize vancomycin resistance by using computer
      software version 7.1 was evaluated. Conventional methods were used for
      identification and agar dilution was used for susceptibility testing, the results
      of which were as follows (presented as number of vancomycin-resistant
      isolates/number of members of that species identified): 219/234 E. faecium, 9/112
      E. faecalis, 2/3 E. mundtii, 0/1 E. durans, 0/1 E. hirae, 0/1 E. raffinosis, and
      0/1 E. avium. Ten enterococci were in the vancomycin-intermediate category (six
      E. gallinarum, two E. casseliflavus, and one each of E. faecium and E. faecalis).
      The Vitek GPI card correctly identified 98% of E. faecium isolates, 99% of E.
      faecalis isolates, and only two isolates of other enterococcal species. The GPS
      TA card was 98% sensitive and 95% specific for the detection of vancomycin
      resistance, generating a total of four very major (1.6%) and five minor errors
      (1.3%).

PMID- 8253982
TI  - Monoclonal antibody specific to virulence-associated 15- to 17-kilodalton
      antigens of Rhodococcus equi.
AB  - Virulent Rhodococcus equi produces 15- to 17-kDa surface protein antigens. These
      antigens are used as markers to identify virulent R. equi isolates from foals and
      their environment by Western blot (immunoblot) analysis with naturally infected
      foal serum. In the present study, a monoclonal antibody (MAb; 10G5) was generated
      against the 15- to 17-kDa antigens excised from sodium dodecyl sulfate
      polyacrylamide gels to develop sensitive and specific immunoblot assays for the
      identification of virulent R. equi. MAb 10G5 strongly reacted with R. equi ATCC
      33701 and L1, which expressed 15- to 17-kDa antigens by Western blot, colony
      blot, and dot immunobinding assays, but it did not react with strains ATCC 33701P
      and L1P-, which lacked the antigens. For identification of virulent R. equi,
      clinical and environmental isolates were tested by these assays with the MAb, and
      all virulent strains were successfully identified; these strains possessed
      virulence plasmids. These results suggest that the MAb is a useful reagent for
      the identification of virulent R. equi.

PMID- 8253983
TI  - Direct DNA probe assay for Neisseria gonorrhoeae in pharyngeal and rectal
      specimens.
AB  - The direct detection of gonococcal DNA in rectal and pharyngeal specimens was
      evaluated by using a DNA probe-based assay (Gen-Probe, Inc., San Diego, Calif.).
      Rectal (234) and pharyngeal (608) swab specimens were obtained from 249 men and
      372 women attending sexually transmitted disease clinics in Las Vegas and Reno,
      Nevada. The prevalence of gonococcal infection by culture at the pharyngeal and
      rectal sites was 2.9% (16 of 548 specimens) in women and 2.7% (8 of 294
      specimens) in men. No false-positive reactions were observed among the 234 rectal
      specimens tested. Two probe-positive, culture-negative specimens were detected
      among the 361 pharyngeal specimens obtained from women. Both of these samples
      were confirmed as Neisseria gonorrhoeae by a probe competition assay. The overall
      correlation of the DNA probe test with pharyngeal and rectal cultures was 99.4%
      (837 of 842 cultures), with a sensitivity of 87.5% (21 of 24 cultures) and
      specificity of 99.7% (816 of 818 cultures). The positive and negative predictive
      values of the DNA assay were 91.3 and 99.8%, respectively. The direct DNA probe
      assay provides an alternative to culture screening for rectal and/or pharyngeal
      gonococcal infections.

PMID- 8253984
TI  - Evaluation of MicroScan rapid panels for detection of high-level aminoglycoside
      resistance in enterococci.
AB  - The ability of MicroScan rapid panels to detect high-level aminoglycoside
      resistant enterococci was evaluated. By agar dilution, 46 of 139 isolates were
      susceptible to gentamicin (GNT) and streptomycin (STRP); the rest were highly
      resistant to one or both agents. Rapid panels detected 97.5% of STRP- and GNT
      resistant isolates and had a specificity of 95.6%. Detection of resistance by
      conventional panels at 18 h was 64.6% for STRP and 90.2% for GNT.

PMID- 8253985
TI  - Simple and rapid two-step polymerase chain reaction for diagnosis of Pneumocystis
      carinii infection.
AB  - Two amplification steps were made to detect Pneumocystis carinii DNA by
      polymerase chain reaction (PCR). pAZ102-E and pAZ102-H (standard PCR), pAZ102-L2
      (sense), and pAZ102-E (antisense) (two-step PCR) were used as primers. The
      amplification products were analyzed by ethidium bromide. After the two-step PCR,
      ethidium bromide detected all samples positive by oligohybridization after one
      amplification step. Our two-step PCR is a rapid, cost-effective, and clinically
      suitable method for the detection of P. carinii infection.

PMID- 8253986
TI  - Study of growth requirements other than cysteine of naturally occurring
      Escherichia coli and Klebsiella spp. auxotrophic for cysteine.
AB  - Cysteine remains the preferred supplement for cultivation of Cys- auxotrophs in
      vitro. Methionine, which reduced cysteine requirements, and branched-chain amino
      acids, which decreased cysteine toxicity, were identified as the components of
      casein hydrolysate responsible for growth enhancement by this additive.
      Glutathione and DL-homocysteine can be substituted for cysteine. Accumulation of
      these compounds in patients with renal impairment may favor selection of Cys-
      strains in vivo.

PMID- 8253987
TI  - Utilization review of the use of BACTEC PLUS high-volume blood culture bottles.
AB  - The BACTEC PLUS 26 (NR26) (Becton Dickinson, Towson, Md.) high-volume blood
      culture bottle replaced the less expensive smaller-volume NR6A bottle in our
      hospital. An audit carried out several months after their introduction revealed
      that only 17.5% of the NR26 bottles received the required blood volume. Several
      audits and educational programs were required in order to achieve a compliance
      rate of > 60%.

PMID- 8253988
TI  - Evaluation of a genetically engineered cell line and a histochemical beta
      galactosidase assay to detect herpes simplex virus in clinical specimens.
AB  - A novel histochemical method was compared with a cytopathic effect (CPE) assay
      for the identification of herpes simplex virus (HSV) in clinical specimens. The
      method utilizes a stably transformed cell line (BHKICP6LacZ-5) that expresses
      beta-galactosidase only after infection with HSV. A total of 96 specimens
      submitted to our diagnostic virology laboratory were analyzed. Thirty-one
      specimens contained HSV as evidenced by positive CPE, and all were positive for
      beta-galactosidase staining. CPE were not evident for 2 or more days in 15 of the
      31 positive specimens, whereas the histochemical stain was positive in all 31
      positives by 16 to 24 h. This preliminary study shows that the BHKICP6LacZ-5 cell
      line can be used in a rapid, sensitive, and specific assay for the detection of
      HSV in clinical specimens.

PMID- 8253989
TI  - Profile of Escherichia coli O157:H7 pathogen responsible for hamburger-borne
      outbreak of hemorrhagic colitis and hemolytic uremic syndrome in Washington.
AB  - We analyzed Escherichia coli O157:H7 isolates from stool samples of five patients
      who had bloody diarrhea and were infected during a large food-borne outbreak of
      hemorrhagic colitis in Washington state. The isolates were assessed for Shiga
      like toxin profile, adherence and plasmid traits, mouse virulence, capsule, and
      enterohemolysin production. The profiles of the five isolates were
      indistinguishable from each other and similar to that of E. coli O157:H7 strain
      EDL933, an organism responsible for a similar hamburger-associated food poisoning
      episode in 1982.

PMID- 8253990
TI  - Isolation of Helicobacter pylori from saliva.
AB  - Helicobacter pylori was grown in low numbers from the saliva of one of nine
      patients who were positive for gastric H. pylori. The saliva-derived isolate from
      this patient was identical to the antral biopsy-derived isolate from the same
      patient and differed from isolates cultured from the antral biopsies of all other
      patients by soluble-protein electrophoresis, restriction endonuclease DNA
      analysis, and Southern blot hybridization. This is the first observation, to our
      knowledge, of the recovery of viable H. pylori from saliva.

PMID- 8253991
TI  - Strains of Mycobacterium terrae complex which react with DNA probes for M.
      tuberculosis complex.
AB  - Following a recent report that two isolates of Mycobacterium terrae complex had
      given positive reactions with M. tuberculosis complex DNA probes, a joint study
      was undertaken to determine the extent of these findings in the clinical culture
      collection holdings of two state health laboratories. A total of 117 M. terrae
      complex strains (identified by standard biochemical methods) were subjected to M.
      tuberculosis complex probe testing with the two then-available kits (from
      Syngene, Inc., and Gen-Probe, Inc.). In addition to the two original isolates
      first reported, two further M. terrae complex isolates were found to react with
      the M. tuberculosis complex probes. Two modifications of the Accuprobe (Gen
      Probe, Inc.) test method were evaluated. Extension of the selection time to 8 min
      was the most convenient modification and rendered the M. terrae complex isolates
      negative when tested with the Accuprobe M. tuberculosis complex probe. However,
      the effects of increased selection time on the overall sensitivity of the M.
      tuberculosis complex probe require further study.

PMID- 8253992
TI  - Evaluation of reliability of pooling stool specimens from different patients and
      detection of Giardia lamblia antigen by microtiter enzyme-linked immunosorbent
      assay.
AB  - We have shown that stool samples from different patients can be pooled at a 1:2
      dilution and reliably assayed for Giardia lamblia antigen by a commercial
      microtiter enzyme-linked immunosorbent assay (ELISA) system (LMD Laboratories,
      Inc., Carlsbad, Calif.). Laboratories can reduce reagent costs by pooling
      specimens submitted for the detection of Giardia antigen by ELISA.

PMID- 8253993
TI  - Utility of a respiratory virus panel containing a monoclonal antibody pool for
      screening of respiratory specimens in nonpeak respiratory syncytial virus season.
AB  - An indirect immunofluorescence respiratory virus panel containing monoclonal
      antibodies directed against respiratory syncytial virus, parainfluenza virus
      types 1, 2, and 3, adenovirus, and influenza viruses A and B was used to screen
      specimens in the nonpeak respiratory syncytial virus seasons in 1989 and 1990.
      The results indicate that the respiratory virus panel is fairly sensitive (79%)
      and very specific (99%) for the detection of respiratory viruses directly in
      clinical specimens during these time periods.

PMID- 8253994
TI  - Effect of iron-limiting conditions on growth of clinical isolates of
      Acinetobacter baumannii.
AB  - Different clinical isolates of Acinetobacter baumannii, typed by plasmid profile,
      were able to grow in iron-chelated medium by secreting iron-regulated
      siderophores. This iron-scavenging phenotype was associated with the production
      of iron-repressible catechol. Siderophore utilization bioassays showed the
      presence of 2,3-dihydroxybenzoic acid in the growth medium, and neither
      enterobactin nor aerobactin was detected in culture supernatants obtained under
      iron-deficient conditions.

PMID- 8253995
TI  - Use of the Quantitative Buffy Coat system for detection of parasitemia in
      patients with babesiosis.
AB  - Quantitative Buffy Coat analysis and blood smears were performed on a total of 47
      blood samples. The technique showed 100% correlation with the blood smears in 9
      samples containing babesia and 10 samples containing malaria, with some
      differential features distinguishing the two infections. Quantitative Buffy Coat
      analysis provides a simple and rapid method for the detection of parasitemia in
      cases of babesiosis.

PMID- 8253996
TI  - Multilocus enzyme typing of Cryptococcus neoformans.
AB  - Multilocus enzyme electrophoresis was adapted for subtyping Cryptococcus
      neoformans. The two cryptococcal varieties were clearly distinguishable. Isolates
      of the C. neoformans var. neoformans were sorted according to serotype and were
      sorted into four to five subtypes within each serotype. Nearly no two isolates of
      the C. neoformans var. gattii displayed the same enzyme electrophoretic type.
      This method may be a useful adjunct to current methods for classification and
      epidemiologic studies of cryptococci.

PMID- 8253997
TI  - Cytomegalovirus antigenemia: clinical correlations in transplant recipients and
      in persons with AIDS.
AB  - We evaluated a rapid immunoperoxidase technique for the detection of
      cytomegalovirus (CMV) antigenemia in peripheral blood neutrophils of 56
      transplant recipients (117 specimens) and 36 persons with AIDS (59 specimens).
      Antigenemia was 92% sensitive and 98% specific for the detection of clinical CMV
      infection in transplant recipients and 100% sensitive and 86% specific in persons
      with AIDS. Overall, CMV antigenemia was a more rapid and sensitive method for the
      detection of clinical CMV infection than either shell vial culture or
      conventional tube culture of blood.

PMID- 8253998
TI  - Interpretive accuracy of the disk diffusion method for testing newer orally
      administered cephalosporins against Morganella morganii.
AB  - Eight newer orally administered cephems (cefdinir, cefetamet, cefixime,
      cefpodoxime, cefprozil, ceftibuten, cefuroxime, and loracarbef) were tested
      against 100 clinical strains of Morganella morganii to determine the extent of
      serious interpretive very major (false-susceptible) errors when current criteria
      for the disk diffusion test are applied. Agar dilution MICs and disk diffusion
      tests were performed as recommended by the National Committee for Clinical
      Laboratory Standards (Villanova, Pa.) (NCCLS), and the methods were compared by
      regression analysis using the method of least squares and by error rate bounding.
      The following results are listed in the order of increasing error rates:
      cefdinir, loracarbef, and cefprozil, < or = 1% very major error; ceftibuten, 8%
      minor errors; cefuroxime, 21% minor errors; cefixime, cefpodoxime, and cefetamet,
      very major errors of 15, 24, and 36%, respectively. M. morganii produces
      unacceptable rates of test error with cefuroxime, cefixime, cefpodoxime, and
      cefetamet. The latter two cephalosporins currently have NCCLS table footnote
      warnings covering the problem observed with this organism. The inclusion of
      cefuroxime and cefixime in the NCCLS table footnote is strongly recommended.

PMID- 8253999
TI  - Discriminatory power of typing schemes based on Simpson's index of diversity for
      Neisseria gonorrhoeae.
AB  - Simpson's index of diversity was used to produce a single numerical value to
      compare the abilities of single or combined typing schemes to discriminate
      between unrelated isolates. This calculation was used to compare the
      discriminating power of auxotype and serovar determination and plasmid content
      analysis, either singly or in combination, for Neisseria gonorrhoeae isolates
      having different antimicrobial susceptibilities (i.e., antibiotic-susceptible
      isolates and those that produce penicillinase, carry plasmid-mediated resistance
      to tetracycline, have chromosomally mediated penicillin resistance, or both
      produce penicillinase and carry plasmid-mediated resistance to tetracycline).
      Plasmid content analysis and auxotype determination produced the lowest level of
      discrimination, while a combination of auxotype and serovar typing schemes
      generally provided higher levels of discrimination. Addition of plasmid content
      analysis to auxotype and serovar typing provided additional discrimination only
      with penicillinase-producing isolates. For isolates that carried plasmid-mediated
      resistance to tetracycline, isolates that were tetracycline resistant, isolates
      that both produced penicillinase and carried plasmid-mediated resistance to
      tetracycline, or isolates that had chromosomally mediated penicillin resistance,
      none of the typing methods produced high discriminatory indices, indicating that
      these isolates are probably derived from relatively few clones.

PMID- 8254000
TI  - Clinical isolates of Campylobacter mucosalis.

PMID- 8254001
TI  - Serologic diagnosis of tuberculosis through assays of lipoarabinomannan antigen
      or antibody or lysozyme level.

PMID- 8254002
TI  - Pseudomonas folliculitis from sponges promoted as beauty aids.

PMID- 8254003
TI  - Public health is more important than health care.

PMID- 8254004
TI  - Toward a new, "independent-cooperative model" of international health.
AB  - This article comments on the spirited North-South debate on international health
      which took place in Quebec, Canada in March 1991. This debate focused on a
      comprehensive critique of the current "classical" approach to international
      health adhered to by the central industrial countries, and vigorous affirmation
      of the need for a new, "independent-cooperative model" of international health.
      Emphasis is placed on the need for new leadership to transform international
      health from a field of dominance and dependence to one of independence and
      cooperation.

PMID- 8254005
TI  - Occupational health: a discipline out of focus.
AB  - This article first examines three areas of occupational health: the work of the
      International Commission on Radiological Protection (ICRP), the work on chemicals
      of the American Conference of Governmental Industrial Hygienists (ACGIH), and the
      International Labour Organization (ILO) Convention and Recommendation on
      Occupational Health Services. All three areas are criticized, using the notion of
      a "scientific strategy" which is the use of bodies of scientific knowledge and
      techniques in approaching occupational health. In the first two areas, it is
      contended that a misguided scientific strategy has been adopted which is a
      comment on the role of scientists in policy-making. In the third case, it is
      argued that the Convention and Recommendation emphasize the remedial aspects of
      occupational health to the detriment of the preventive side, a reflection of the
      undue influence of industrial medicine on occupational health. A proper approach
      to occupational health would make very different demands on science and would
      employ engineering techniques at the expense of the medical disciplines. As it
      is, occupational health is out of focus.

PMID- 8254006
TI  - Rethinking perinatal policy: history and evaluation of minimum volume and level
      of-care standards.
AB  - Two standards have played a dominant role in policies to organize U.S. perinatal
      care. Minimum volume (or size) and service levels according to technical capacity
      have been major components of perinatal regionalization and other reorganization
      efforts. These standards are consistent with structural definitions of quality of
      care, but not necessarily with quality definitions according to outcome.
      Empirical research has not demonstrated a general association between the
      standards and improved perinatal outcomes, although it has demonstrated improved
      outcomes for very low birthweight babies. The standards have contributed to the
      growth and financial stability of tertiary-level services, but economy in terms
      of lower unit costs has also not been demonstrated. These discrepancies between
      research findings and the paradigm of a system of large, complex centers have led
      to conceptual errors in explaining findings, but they have also led to a
      recognition of uncertainty concerning perinatal service organization.

PMID- 8254007
TI  - The burdens of race and history on Black Americans' attitudes toward needle
      exchange policy to prevent HIV disease.
AB  - We must enter the second decade of AIDS with the knowledge that existing public
      health efforts have failed to stop the disproportionate spread of HIV disease
      among Americans of African descent. This article presents the cold
      epidemiological facts which lay bare the moral tragedy that Black Americans are
      being killed by a disease which is almost totally preventable. This paper
      discusses the primary behavioral risk factors for HIV infection and the context
      in which HIV disease emerged in the 1980s. Additionally, we present results from
      cross-sectional surveys of selected black populations to demonstrate how AIDS
      knowledge deficits and attitudinal barriers have shaped the perceptions of Black
      Americans toward needle exchange programs as an HIV prevention strategy advocated
      by public health authorities. A model that may be utilized to educate the Black
      community and facilitate their involvement in the development of needle exchange
      policy is described.

PMID- 8254008
TI  - Public health and working children in twentieth-century America: an historical
      overview.
AB  - Throughout this century, concern for the health of America's youth has been a
      driving force in the long fight to regulate child labor. The prevalence of
      children in dangerous trades like mining and mill work at the start of the
      century was a major factor behind the creation of a national child labor reform
      movement. Not until the Fair Labor Standards Act of 1938, however, were reformers
      able to secure universal age, hour and health standards for working youngsters.
      In the decades following World War 2, child labor dramatically declined in the
      United States. But new waves of immigration in the 1980s, along with increased
      participation of high school students in the service sector, have contributed to
      a resurgence in juvenile employment and focused renewed attention on the health
      risks faced by minors in the workplace.

PMID- 8254009
TI  - Injury surveillance: should it be a concern to developing countries?
AB  - Injuries have now become a recognizable public health problem in developing
      countries. However, no definite policies regarding their surveillance and control
      are yet available in most of these countries. This paper, using Ghana as a
      prototype, examines the need for policy and action which has been accentuated in
      recent times by public outcry. The paper also provides some recommendations to
      solve this problem: the urgent need to initiate programs such as needs
      assessment, the establishment of a surveillance system for injuries at various
      levels of health services, creation of public awareness and provision of health
      education, and the institution of simple first-aid measures. Specific policies
      regarding injuries from motor vehicle accidents and fires are also given.

PMID- 8254010
TI  - A slice of PAI.

PMID- 8254011
TI  - Beta-adrenergic receptors in heart failure.

PMID- 8254012
TI  - A major advance in the use of growth factors to enhance wound healing.

PMID- 8254013
TI  - Heavy traffic at a dual-purpose human mitochondrial tRNA gene.

PMID- 8254014
TI  - In vivo gene transfer, Koch's postulates, and renal disease.

PMID- 8254015
TI  - The effects of 2-year treatment with the aminobisphosphonate alendronate on bone
      metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman
      primates.
AB  - This study examined the effect of 2 yr of treatment with the aminobisphosphonate
      alendronate (ALN) (0.05 or 0.25 mg/kg i.v. ALN every 2 wk) on estrogen deficiency
      bone loss and bone strength changes in ovariectomized (OVX) baboons (n = 7 per
      group) and the ALN mode of action at the tissue level. Biochemical markers of
      bone turnover increased in OVX animals and were maintained by ALN treatment at
      non-OVX levels (low dose) or below (high dose). 2 yr of treatment produced no
      cumulative effects on bone turnover markers. Histomorphometry showed a marked
      increase in cancellous bone remodeling in OVX animals. Activation frequency
      increased from 0.48 to 0.86 per yr (L5 vertebra), and the osteoid surfaces from 9
      to 13.5% (P < 0.05). No changes were observed in eroded and osteoclast surfaces.
      ALN treatment decreased activation frequency and indices of bone formation to
      control levels (low dose) or below (high dose), did not change indices of
      mineralization, and increased bone mineral density (BMD) in the lumbar vertebrae
      (L2-L4) by 15% at 0.25 mg/kg (P < 0.05), relative to vehicle-treated animals. The
      mean strength of cancellous bone (L4) increased by 44% (low ALN dose) and 100%
      (high dose), compared with vehicle. The strength of individual bones correlated
      with the square of the L2-L4 BMD (r = 0.91, P < 0.0034). In conclusion, ALN
      treatment reversed the effects of ovariectomy on cancellous bone turnover and
      increased bone mass and bone strength in baboons.

PMID- 8254016
TI  - Human and murine dermis contain dendritic cells. Isolation by means of a novel
      method and phenotypical and functional characterization.
AB  - Dendritic cells (DC) comprise a system of cells in lymphoid and nonlymphoid
      organs that are specialized to present antigens and to initiate primary T cell
      responses. The Langerhans cell of the epidermis is used as a prototype for
      studies of DC in the skin. We have characterized a population of DC in human
      dermis, one of the first examples of these cells in nonlymphoid organs other than
      epidermis. To identify their distinct functions and phenotype, we relied upon the
      preparation of enriched populations that emigrate from organ explants of dermis.
      The dermal cells have the following key features of mature DC: (a) sheet-like
      processes, or veils, that are constantly moving; (b) very high levels of surface
      MHC products; (c) absence of markers for macrophages, lymphocytes, and
      endothelium; (d) substantial expression of adhesion/costimulatory molecules such
      as CD11/CD18, CD54 (ICAM-1), B7/BB1, CD40; and (e) powerful stimulatory function
      for resting T cells. Dermal DC are fully comparable to epidermis-derived DC,
      except for the lack of Birbeck granules, lower levels of CD1a, and higher levels
      of CD36. DC were also detected in explants of mouse dermis. We conclude that
      cutaneous DC include both epidermal and dermal components, and suggest that other
      human nonlymphoid tissues may also serve as sources of typical immunostimulatory
      DC.

PMID- 8254017
TI  - Glomerulosclerosis induced by in vivo transfection of transforming growth factor
      beta or platelet-derived growth factor gene into the rat kidney.
AB  - Glomerulosclerosis, a final common lesion of various glomerular diseases, is
      characterized by mesangial cell proliferation and extracellular matrix (ECM)
      expansion. TGF-beta and PDGF are known to play a critical role in the regulation
      of ECM metabolism and mesenchymal cell proliferation, respectively. However,
      there is little evidence to demonstrate the direct role of each of these growth
      factors in the pathogenesis of glomerulosclerosis. Using an in vivo transfection
      technique, we could realize the selective overexpression of single growth factor
      in the kidney. The introduction of either TGF-beta or PDGF-B gene alone into the
      kidney induced glomerulosclerosis, although the patterns of action of these
      growth factors were different; TGF-beta affected ECM accumulation rather than
      cell proliferation and PDGF affected the latter rather than the former.

PMID- 8254019
TI  - Potential role for interleukin-10 in the immunosuppression associated with kala
      azar.
AB  - Patients with acute kala azar are generally nonreactive in a number of
      immunologic assays, including T cell proliferation and generation of macrophage
      activating cytokines, principally IFN-gamma, in response to leishmania antigens
      in vitro. To test for potential immunosuppressive factors, a series of T cell
      lines and clones were established from patients with acute kala azar, from
      patients after chemotherapy for kala azar, and from skin test-positive adults
      from the same endemic region. Although CD4+ T cell lines and clones could be
      readily established from the skin test-positive adults, lines and clones from
      acute or treated patients were heavily biased in expression of CD8+. The CD8+
      cells from acute patients did not themselves release cytokines in response to
      leishmania antigens in vitro, but markedly affected the cytokine profile of
      peripheral blood mononuclear cells isolated 1 yr later after recovery. Addition
      of the CD8+ cells caused inhibition of lymphoproliferation and IFN-gamma release,
      with augmentation of IL-6 and IL-10 release. The inhibitory effects of the CD8+
      cells could be partially abrogated by antibodies to IL-10 but not by antibodies
      to IL-4. Analysis of four patients with acute kala azar demonstrated release of
      IL-10 that could not be demonstrated in supernatants from asymptomatic skin test
      positive individuals. Generation of IL-10 may contribute to the profound
      suppression of IFN-gamma release that occurs during kala azar due to Leishmania
      chagasi.

PMID- 8254018
TI  - Release of ceramide after membrane sphingomyelin hydrolysis decreases the
      basolateral secretion of triacylglycerol and apolipoprotein B in cultured human
      intestinal cells.
AB  - The effect of sphingomyelin hydrolysis on triacylglycerol-rich lipoprotein
      secretion was examined in the human intestinal cell line, CaCo-2. Addition of
      sphingomyelinase decreased sphingomyelin and phosphatidylethanolamine by 60 and
      20%, respectively. Sphingomyelin hydrolysis decreased the basolateral secretion
      of triacylglycerol mass, newly synthesized triacylglycerol, and apo B mass. Pulse
      chase experiments with [35S]methionine demonstrated a decrease in apo B synthesis
      and a marked decrease in apo B100 and apo B48 secretion without altering apo A1
      secretion. Sphingomyelin hydrolysis did not change apo B mRNA levels nor apo B
      turnover. Phosphatidylcholine-specific phospholipase C did not decrease apo B
      synthesis or its basolateral secretion. Membrane protein kinase C (PKC) activity
      was decreased twofold after sphingomyelin hydrolysis. The PKC inhibitor
      staurosporine decreased apo B mass and newly synthesized apo B secretion.
      Sphingomyelinase and staurosporine together caused an additional decrease in apo
      B secretion suggesting that sphingomyelin hydrolysis decreased apo B secretion
      independently of its effect on PKC activity. Moreover, conditions that increase
      PKC activity did not increase apo B secretion. Cell-permeable analogs of ceramide
      decreased immunoreactive apo B secretion. Sphingosine was without effect. The
      hydrolysis of membrane sphingomyelin by intestinal or pancreatic neutral
      sphingomyelinase may lead to the accumulation of cellular ceramide, which, in
      turn, could inhibit triacylglycerol-rich lipoprotein secretion.

PMID- 8254020
TI  - Regional myocardial downregulation of the inhibitory guanosine triphosphate
      binding protein (Gi alpha 2) and beta-adrenergic receptors in a porcine model of
      chronic episodic myocardial ischemia.
AB  - Regional myocardial ischemia is associated with increased levels of adenosine and
      norepinephrine, factors that may alter activation of the beta-adrenergic receptor
      (beta AR)-G protein-adenylyl cyclase pathway in the heart. We have used the
      ameroid constrictor model to determine whether alterations in myocardial signal
      transduction through the beta AR-G protein-adenylyl cyclase pathway occur in the
      setting of chronic episodes of reversible ischemia. Pigs were instrumented with
      ameroid occluders placed around the left circumflex coronary artery. 5 wk later,
      after ameroid closure, flow and function were normal in the ischemic bed, but
      flow (P = 0.001) and function (P < 0.03) were abnormal when metabolic demands
      were increased. The ischemic bed showed a reduction in myocardial beta AR number
      (P < 0.005). Despite regional downregulation of myocardial beta AR number,
      adenylyl cyclase activity was similar in the ischemic and control beds.
      Quantitative immunoblotting showed that the cardiac inhibitory GTP-binding
      protein, Gi alpha 2, was decreased in the ischemic bed (P = 0.02). In contrast,
      the cardiac stimulatory GTP-binding protein, Gs alpha, was increased in
      endocardial sections from the ischemic bed (P = < 0.05). Decreased Gi alpha 2
      content was associated with decreased inhibition of adenylyl cyclase. Reduced Gi
      alpha 2 content, in conjunction with increased Gs alpha content in the
      endocardium, may provide a means by which adrenergic activation is maintained in
      the setting of chronic episodic myocardial ischemia.

PMID- 8254021
TI  - Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist
      (OPC-31260) in men.
AB  - Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin
      receptors (V2) may be useful in treating water-retaining diseases. The effects of
      intravenous administration of a newly developed nonpeptide, selective V2
      antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of
      healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide
      and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for
      the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute
      increase in the cumulative response in the urine to the highest doses of OPC
      31260 was not significantly different from that to furosemide. The higher doses
      of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between
      minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected
      between minutes 30 and 45). In a marked hypotonic diuresis, mean free water
      clearance of the 4-h urine increased dose proportionally into the positive range,
      reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na
      and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h,
      0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin;
      and the higher doses increased plasma osmolality and plasma Na slightly, but did
      not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced
      a potent aquaretic effect in men.

PMID- 8254022
TI  - Mitochondrial myopathy with succinate dehydrogenase and aconitase deficiency.
      Abnormalities of several iron-sulfur proteins.
AB  - Recently, we described a patient with severe exercise intolerance and episodic
      myoglobinuria, associated with marked impairment of succinate oxidation and
      deficient activity of succinate dehydrogenase and aconitase in muscle
      mitochondria (1). We now report additional enzymatic and immunological
      characterization of mitochondria. In addition to severe deficiency of complex II,
      manifested by reduction of succinate dehydrogenase and succinate:coenzyme Q
      oxidoreductase activities to 12 and 22% of normal, respectively, complex III
      activity was reduced to 37% and rhodanese to 48% of normal. Furthermore, although
      complex I activity was not measured, immunoblot analysis of complex I showed
      deficiency of the 39-, 24-, 13-, and 9-kD peptides with lesser reductions of the
      51- and 18-kD peptides. Immunoblots of complex III showed markedly reduced levels
      of the mature Rieske protein in mitochondria and elevated levels of its precursor
      in the cytosol, suggesting deficient uptake into mitochondria. Immunoreactive
      aconitase was also low. These data, together with the previous documentation of
      low amounts of the 30-kD iron-sulfur protein and the 13.5-kD subunit of complex
      II, compared to near normal levels of the 70-kD protein suggest a more
      generalized abnormality of the synthesis, import, processing, or assembly of a
      group of proteins containing iron-sulfur clusters.

PMID- 8254023
TI  - Impaired hormonal responses to hypoglycemia in spontaneously diabetic and
      recurrently hypoglycemic rats. Reversibility and stimulus specificity of the
      deficits.
AB  - To evaluate the roles of iatrogenic hypoglycemia and diabetes per se in the
      pathogenesis of defective hormonal counterregulation against hypoglycemia in
      insulin-dependent diabetes mellitus (IDDM), nondiabetic, and spontaneously
      diabetic BB/Wor rats were studied using a euglycemic/hypoglycemic clamp. In
      nondiabetic rats, recurrent (4 wk) insulin-induced hypoglycemia (mean daily
      glucose, MDG, 59 mg/dl) dramatically reduced glucagon and epinephrine responses
      by 84 and 94%, respectively, to a standardized glucose fall from 110 to 50 mg/dl.
      These deficits persisted for > 4 d after restoring normoglycemia, and were
      specific for hypoglycemia, with normal glucagon and epinephrine responses to
      arginine and hypovolemia, respectively. After 4 wk of normoglycemia, hormonal
      counterregulation increased, with the epinephrine, but not the glucagon response
      reaching control values. In diabetic BB rats (MDG 245 mg/dl with intermittent
      hypoglycemia), glucagon and epinephrine counterregulation were reduced by 86 and
      90%, respectively. Chronic iatrogenic hypoglycemia (MDG 52 mg/dl) further
      suppressed counterregulation. Prospective elimination of hypoglycemia (MDG 432
      mg/dl) improved, but did not normalize hormonal counterregulation. In diabetic
      rats, the glucagon defect appeared to be specific for hypoglycemia, whereas
      deficient epinephrine secretion also occurred during hypovolemia. We concluded
      that both recurrent hypoglycemia and the diabetic state independently lead to
      defective hormonal counterregulation. These data suggest that in IDDM iatrogenic
      hypoglycemia magnifies preexisting counterregulatory defects, thereby increasing
      the risk of severe hypoglycemia.

PMID- 8254024
TI  - The antiinflammatory mechanism of methotrexate. Increased adenosine release at
      inflamed sites diminishes leukocyte accumulation in an in vivo model of
      inflammation.
AB  - Methotrexate, a folate antagonist, is a potent antiinflammatory agent when used
      weekly in low concentrations. We examined the hypothesis that the antiphlogistic
      effects of methotrexate result from its capacity to promote intracellular
      accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) that, under
      conditions of cell injury, increases local adenosine release. We now present the
      first evidence to establish this mechanism of action in an in vivo model of
      inflammation, the murine air pouch model. Mice were injected intraperitoneally
      with either methotrexate or saline for 3-4 wk during induction of air pouches.
      Pharmacologically relevant doses of methotrexate increased splenocyte AICAR
      content, raised adenosine concentrations in exudates from carrageenan-inflamed
      air pouches, and markedly inhibited leukocyte accumulation in inflamed air
      pouches. The methotrexate-mediated reduction in leukocyte accumulation was
      partially reversed by injection of adenosine deaminase (ADA) into the air pouch,
      completely reversed by a specific adenosine A2 receptor antagonist, 3,7-dimethyl
      1-propargylxanthine (DMPX), but not affected by an adenosine A1 receptor
      antagonist, 8-cyclopentyl-dipropylxanthine. Neither ADA nor DMPX affected
      leukocyte accumulation in the inflamed pouches of animals treated with either
      saline or the potent antiinflammatory steroid dexamethasone. These results
      indicate that methotrexate is a nonsteroidal antiinflammatory agent, the
      antiphlogistic action of which is due to increased adenosine release at inflamed
      sites.

PMID- 8254025
TI  - T cell receptor V beta gene bias in rheumatoid arthritis.
AB  - Polymerase chain reaction (PCR) technology was employed to examine peripheral
      blood and synovial T cells in patients with rheumatoid arthritis (RA) for biased
      utilization of T cell receptor (TCR) variable region (V) genes. Oligonucleotide
      primers specific for individual TCR V beta gene families were used to amplify TCR
      gene products in a semiquantitative assay of their relative utilization in
      unselected T cell populations. Mean V beta expression in 24 RA peripheral blood
      samples was very similar to that in a panel of 15 normal subjects, except for a
      slight decrease in V beta 13.2 expression. V beta utilization in 8 RA synovial
      tissue samples and 13 synovial fluid samples was compared to simultaneously
      obtained blood samples. Although heterogeneous patterns of skewed V beta
      utilization were observed, several significant trends emerged. By a number of
      approaches to data analysis, a statistically significant increase in expression
      of V beta 6 and V beta 15 in synovial T cells was documented. In addition,
      increased synovial expression of V beta 14 was found, but only in the synovial
      fluid samples. Reduced expression of V beta 1, V beta 4, V beta 5.1, V beta 10, V
      beta 16, and V beta 19 was also observed in synovial T cells. These results
      indicate that biased V beta gene utilization in different peripheral compartments
      of RA patients can be observed in unselected T cell populations, and are
      consistent with the conclusion that populations of T cells expressing these V
      beta gene products may be involved in the pathogenesis of the disease.

PMID- 8254026
TI  - A splice junction mutation causes deletion of a 72-base exon from the mRNA for
      lysosomal acid lipase in a patient with cholesteryl ester storage disease.
AB  - The genetic defect leading to cholesteryl ester storage disease (CESD) has been
      determined in a 12-yr-old patient. Lysosomal acid lipase (LAL) activity in
      cultured skin fibroblasts was reduced to approximately 9% of control fibroblasts.
      Plasma cholesterol (255 mg/dl) and LDL-cholesterol (215 mg/dl) were elevated
      whereas HDL-cholesterol was reduced (19 mg/dl). Triglycerides were moderately
      elevated (141 mg/dl). There were no clinical abnormalities with the exception of
      hepatosplenomegaly. Both parents have reduced LAL activity in white blood cells.
      PCR analysis of the LAL mRNA from the propositus revealed a single slightly
      smaller mRNA species in skin fibroblasts as well as in leukocytes. The mother of
      the patient and his older brother had two mRNA species: one of normal size and
      one of the same size as the propositus. The father has a LAL mRNA of normal size
      only. Sequence analysis of a PCR-amplified cDNA fragment showed a 72-bp in-frame
      deletion resulting in the loss of the codons for amino acids 254-277. Analysis of
      genomic DNA revealed that the 72 bp represent an exon, indicating that the
      deletion in the mRNA is caused by defective splicing. Sequence analysis of the
      patient's genomic DNA revealed a G-->A substitution in the last nucleotide of the
      72-bp exon in one of his alleles. The mutant allele was shown to cosegregate with
      the truncated mRNA in the pedigree, providing further evidence that the G-->A
      substitution causes aberrant splicing and exon skipping. No normal-sized mRNA is
      detectable in the propositus even though he is not homozygous for the splice site
      mutation. This can be only accounted for by assuming that he is a compound
      heterozygote with a null allele inherited from his father. In summary, the data
      presented provide evidence that deletion of the codons for amino acids 254-277 in
      the LAL mRNA in combination with a null allele cause the clinical expression of
      CESD in our patient.

PMID- 8254027
TI  - Reduced beta 1 receptor messenger RNA abundance in the failing human heart.
AB  - Heart failure in humans is characterized by alterations in myocardial adrenergic
      signal transduction, the most prominent of which is down-regulation of beta 1
      adrenergic receptors. We tested the hypothesis that down-regulation of beta 1
      adrenergic receptors in the failing human heart is related to decreased steady
      state levels of beta 1 receptor mRNA. Due to the extremely low abundance of beta
      1 receptor mRNA, measurements were possible only by quantitative polymerase chain
      reaction (QPCR) or by RNase protection methods. Because the beta 1 receptor gene
      is intronless and beta 1 receptor mRNA abundance is low, QPCR yielded genomic
      amplification in total RNA, and mRNA measurements had to be performed in poly
      (A)(+)-enriched RNA. By QPCR the concentration of beta 1 receptor mRNA varied
      from 0.34 to 7.8 x 10(7) molecules/microgram poly(A)(+)-enriched RNA, and the
      assay was sensitive to 16.7 zeptomol. Using 100-mg aliquots of left ventricular
      myocardium obtained from organ donors (nonfailing ventricles, n = 12) or heart
      transplant recipients (failing ventricles, n = 13), the respective beta 1 mRNA
      levels measured by QPCR were 4.2 +/- 0.7 x 10(7)/micrograms vs. 2.10 +/- 0.3 x
      10(7)/micrograms (P = 0.006). In these same nonfailing and failing left
      ventricles the respective beta 1-adrenergic receptor densities were 67.9 +/- 6.9
      fmol/mg vs. 29.6 +/- 3.5 fmol/mg (P = 0.0001). Decreased mRNA abundance in the
      failing ventricles was confirmed by RNase protection assays in total RNA, which
      also demonstrated a 50% reduction in beta 1 message abundance. We conclude that
      down-regulation of beta 1 receptor mRNA contributes to down-regulation of beta 1
      adrenergic receptors in the failing human heart.

PMID- 8254028
TI  - Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by
      homologous recombination and characterization.
AB  - Homozygous plasminogen activator inhibitor-1 (PAI-1)-deficient (PAI-1-/-) mice
      were generated by homologous recombination in D3 embryonic stem cells. Deletion
      of the genomic sequences encompassing the transcription initiation site and the
      entire coding regions of murine PAI-1 was demonstrated by Southern blot analysis.
      A 3.0-kb PAI-1-specific mRNA was identified by Northern blot analysis in liver
      from PAI-1 wild type (PAI-1+/+) but not from PAI-1-/- mice. Plasma PAI-1 levels,
      measured 2-4 h after endotoxin (2.0 mg/kg) injection were 63 +/- 2 ng/ml, 30 +/-
      10 ng/ml, and undetectable (< 2 ng/ml) in PAI-1+/+, heterozygous (PAI-1+/-) and
      PAI-1-/- mice, respectively (mean +/- SEM, n = 4-11). PAI-1-specific
      immunoreactivity was demonstrable in kidneys of PAI-1+/+ but not of PAI-1-/-
      mice. SDS-gel electrophoresis of plasma incubated with 125I-labeled recombinant
      human tissue-type plasminogen activator revealed an approximately 115,000-M(r)
      component with plasma from endotoxin-stimulated (0.5 mg/kg) PAI-1+/+ but not from
      PAI-1-/- mice, which could be precipitated with a polyclonal anti-PAI-1
      antiserum. PAI-1-/- mice were viable, produced similar sizes of litters as PAI
      1+/+ mice, and showed no apparent macroscopic or microscopic histological
      abnormalities.

PMID- 8254029
TI  - Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis,
      thrombosis, and thrombolysis.
AB  - The effects of plasminogen activator inhibitor-1 (PAI-1) gene inactivation on
      hemostasis, thrombosis and thrombolysis were studied in homozygous PAI-1
      deficient (PAI-1-/-) mice, generated by homologous recombination in D3 embryonic
      stem cells. Diluted (10-fold) whole blood clots from PAI-1-/- and from PAI-1 wild
      type (PAI-1+/+) mice underwent limited but significantly different (P < 0.001)
      spontaneous lysis within 3 h (6 +/- 1 vs 3 +/- 1%, respectively). A 25
      microliters 125I-fibrin-labeled normal murine plasma clot, injected into a
      jugular vein, was lysed for 47 +/- 5, 66 +/- 3, and 87 +/- 7% within 8 h in PAI
      1+/+, heterozygous PAI-1-deficient (PAI-1+/-), and PAI-1-/- mice, respectively (P
      = 0.002 for PAI-1+/+ vs PAI-1-/- mice). Corresponding values after pretreatment
      with 0.5 mg/kg endotoxin in PAI-1+/+ and PAI-1-/- mice, were 35 +/- 5 and 91 +/-
      3% within 4 h, respectively (P < 0.001). 11 out of 26 PAI-1+/+ but only 1 out of
      25 PAI-1-/- mice developed venous thrombosis (P = 0.004) within 6 d after
      injection of 10 or 50 micrograms endotoxin in the footpad. Spontaneous bleeding
      or delayed rebleeding could not be documented in PAI-1-/- mice after partial
      amputation of the tail or of the caecum. Thus, disruption of the PAI-1 gene in
      mice appears to induce a mild hyperfibrinolytic state and a greater resistance to
      venous thrombosis but not to impair hemostasis.

PMID- 8254030
TI  - Glutathione, cell proliferation, and 1,3-bis-(2-chloroethyl)-1-nitrosourea in
      K562 leukemia.
AB  - We have pursued our findings of glutathione reductase (GSSG-R) deficiency and
      disturbed glutathione in cancer patients treated with 1,3-bis-(2-chloroethyl)-1
      nitrosourea (BCNU), by investigating how thiol metabolism, cell proliferation,
      and the nitrosourea interact in human K562 leukemia. Fasting cells arrested in G
      greatly increased their reduced glutathione (GSH) in response to growth factors.
      The rise in thiol began after several hours, peaked before DNA synthesis, and
      resulted from increased production. BCNU inactivated GSSG-R rapidly, and later
      retarded, doubled, and greatly prolonged GSH formation before stopping DNA
      synthesis. Pretreatment unlike post treatment with buthionine-S-R-sulfoximine
      (BSO) diminished BCNU's ability to block GSSG-R. Enzyme inhibition decreased with
      falling cellular GSH. In the leukemia system as in vivo, sequential BCNU-induced
      thiol alterations heralded delayed antiproliferative effects. Drug timing
      markedly affected both thiol and DNA syntheses. By destroying GSSG-R and delaying
      the upregulation of thiol synthesis while escalating GSH utilization and
      requirements, the nitrosourea created a striking and previously unrecognized
      window of vulnerability for GSH-dependent processes. During this period, altered
      GSH metabolism could contribute indirectly to BCNU's pleiotropic effects by
      interfering with DNA alkylation repair, glucose decarboxylation, deoxyribose
      formation, and possibly by influencing other aspects of proliferation. Acquired
      GSSG-R deficiency was also an early and sensitive marker for prodrug breakdown
      and activation.

PMID- 8254031
TI  - Regulation of surfactant phosphatidylcholine secretion from alveolar type II
      cells during Pneumocystis carinii pneumonia in the rat.
AB  - We used an immunosuppressed rat model to test the hypothesis that normal
      mechanisms regulating surfactant phosphatidylcholine synthesis and secretion in
      alveolar type II cells are aberrant in Pneumocystis carinii pneumonia. Animal
      groups included: group 1, healthy controls; group 2, immunosuppressed, without
      pneumocystosis; group 3, immunosuppressed with pneumocystosis; group 4,
      immunosuppressed with well-established pneumocystosis treated with trimethoprim
      sulfamethoxazole (TMP-SMX). Type II cells were isolated from rats in each group
      and compared for [3H]choline incorporation into phospholipid and response of the
      type II cells to secretagogues. Incorporation of [3H]choline into phospholipid
      subclasses exhibited significant differences. Incorporation into
      phosphatidylcholine fell from 89.3 +/- 2.2% of total incorporation in group 1
      control rats to 79.6 +/- 3.1% in group 3 rats with P. carinii pneumonia, while
      incorporation into sphingomyelin rose from 5.6 +/- 1.2% in group 1 animals to
      15.2 +/- 2.7% in group 3 rats. Incorporation of [3H]choline into phospholipid
      subclasses in cells from group 2 and group 4 animals was not different from
      incorporation for group 1 animals. Type II cells from group 1 and group 2
      (immunosuppressed control) rats responded appropriately to the secretagogues ATP,
      TPA, and terbutaline with a marked increase in surfactant phosphatidylcholine
      secretion; the effect of ATP was also blocked by the lectin, concanavalin A. In
      contrast, type II cells from group 3 rats failed to respond to the secretagogues
      with a significant increase in phospholipid secretion. Although treatment of
      group 4 rats with TMP-SMX markedly reduced the P. carinii organism burden, type
      II cells from these animals also responded poorly to the secretagogues. The
      depressed type II cell function described here provides a mechanism for the
      observed decrease in surfactant phospholipids from bronchoalveolar lavage fluid
      of experimental animals and patients with P. carinii pneumonia. The data also
      suggest this defect may become irreversible with advanced disease.

PMID- 8254032
TI  - Tumor necrosis factor-alpha mediates changes in tissue protein turnover in a rat
      cancer cachexia model.
AB  - Rats bearing the Yoshida AH-130 ascites hepatoma showed enhanced fractional rates
      of protein degradation in gastrocnemius muscle, heart, and liver, while
      fractional synthesis rates were similar to those in non-tumor bearing rats. This
      hypercatabolic pattern was associated with marked perturbations of the hormonal
      homeostasis and presence of tumor necrosis factor in the circulation. The daily
      administration of a goat anti-murine TNF IgG to tumor-bearing rats decreased
      protein degradation rates in skeletal muscle, heart, and liver as compared with
      tumor-bearing rats receiving a nonimmune goat IgG. The anti-TNF treatment was
      also effective in attenuating early perturbations in insulin and corticosterone
      homeostasis. Although these results suggest that tumor necrosis factor plays a
      significant role in mediating the changes in protein turnover and hormone levels
      elicited by tumor growth, the inability of such treatment to prevent a reduction
      in body weight implies that other mediators or tumor-related events were also
      involved.

PMID- 8254033
TI  - Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor
      gene expression in adrenocorticotropin-producing tumors in vitro.
AB  - To differentiate between ectopic ACTH syndrome and Cushing's disease, gene
      expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC),
      and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's
      disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH
      levels in all patients with Cushing's disease and in five patients with ectopic
      ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders,
      CRH was not detected in tumors that contained no CRH mRNA or that contained only
      long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all
      patients with Cushing's disease and in three patients with ectopic ACTH-producing
      bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH
      increased and Dex decreased ACTH release and POMC mRNA levels in pituitary
      adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in
      carcinoid cells. These results reveal characteristics of ectopic ACTH-producing
      tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition,
      there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH
      (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA
      levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited
      usefulness in differentiating between Cushing's disease and ectopic ACTH
      syndrome.

PMID- 8254034
TI  - Studies of activated GPIIb/IIIa receptors on the luminal surface of adherent
      platelets. Paradoxical loss of luminal receptors when platelets adhere to high
      density fibrinogen.
AB  - The accessibility of activated GPIIb/IIIa receptors on the luminal surface of
      platelets adherent to damaged blood vessels or atherosclerotic plaques is likely
      to play a crucial role in subsequent platelet recruitment. To define better the
      factors involved in this process, we developed a functional assay to assess the
      presence of activated, luminal GPIIb/IIIa receptors, based on their ability to
      bind erythrocytes containing a high density of covalently coupled RGD-containing
      peptides (thromboerythrocytes). Platelets readily adhered to wells coated with
      purified type I rat skin collagen and the adherent platelets bound a dense lawn
      of thromboerythrocytes. With fibrinogen-coated wells, platelet adhesion increased
      as the fibrinogen-coating concentration increased, reaching a plateau at about 11
      micrograms/ml. Thromboerythrocyte binding to the platelets adherent to fibrinogen
      showed a paradoxical response, increasing at fibrinogen coating concentrations up
      to approximately 4-6 micrograms/ml and then dramatically decreasing at higher
      fibrinogen-coating concentrations. Scanning electron microscopy demonstrated that
      the morphology of platelets adherent to collagen was similar to that of platelets
      adherent to low density fibrinogen, with extensive filopodia formation and
      ruffling. In contrast, platelets adherent to high density fibrinogen showed a
      bland, flattened appearance. Immunogold staining of GPIIb/IIIa receptors
      demonstrated concentration of the receptors on the filopodia, and depletion of
      receptors on the flattened portion of the platelets. Thus, there is a paradoxical
      loss of accessible, activated GPIIb/IIIa receptors on the luminal surface of
      platelets adherent to high density fibrinogen. Two factors may contribute to this
      result: engagement of GPIIb/IIIa receptors with fibrinogen on the abluminal
      surface leading to the loss of luminal receptors, and loss of luminal filopodia
      that interact with thromboerythrocytes. These data provide insight into the
      differences in thrombogenicity between surfaces, and may provide a mechanism for
      purposefully passivating platelet-reactive artificial surfaces.

PMID- 8254035
TI  - Familial hypertrophic cardiomyopathy. Microsatellite haplotyping and
      identification of a hot spot for mutations in the beta-myosin heavy chain gene.
AB  - Familial hypertrophic cardiomyopathy (FHC) is a clinically and genetically
      heterogeneous disease. The first identified disease gene, located on chromosome
      14q11-q12, encodes the beta-myosin heavy chain. We have performed linkage
      analysis of two French FHC pedigrees, 720 and 730, with two microsatellite
      markers located in the beta-myosin heavy chain gene (MYO I and MYO II) and with
      four highly informative markers, recently mapped to chromosome 14q11-q12.
      Significant linkage was found with MYO I and MYO II in pedigree 720, but results
      were not conclusive for pedigree 730. Haplotype analysis of the six markers
      allowed identification of affected individuals and of some unaffected subjects
      carrying the disease gene. Two novel missense mutations were identified in exon
      13 by direct sequencing, 403Arg-->Leu and 403Arg-->Trp in families 720 and 730,
      respectively. The 403Arg-->Leu mutation was associated with incomplete
      penetrance, a high incidence of sudden deaths and severe cardiac events, whereas
      the consequences of the 403Arg-->Trp mutation appeared less severe. Haplotyping
      of polymorphic markers in close linkage to the beta-myosin heavy chain gene can,
      thus, provide rapid analysis of non informative pedigrees and rapid detection of
      carrier status. Our results also indicate that codon 403 of the beta-myosin heavy
      chain gene is a hot spot for mutations causing FHC.

PMID- 8254036
TI  - Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human
      atherosclerotic lesions of the aorta.
AB  - Osteopontin is a phosphorylated, sialic acid-rich, noncollagenous bone matrix
      protein containing the Arg-Gly-Asp-Ser amino acid sequence responsible for cell
      adhesion. The protein strongly binds to hydroxyapatite and play an important role
      in calcification. Expression of osteopontin mRNA was analyzed in human aortic
      atherosclerotic lesion by Northern blot hybridization, as well as by in situ
      hybridization. The expression of osteopontin mRNA was detected in 24 out of 25
      samples of aorta obtained from 17 autopsy cases, but not in one normal aortic
      sample. The magnitude of expression was proportional to the stage of
      atherosclerosis. In situ hybridization revealed that the cells expressing
      osteopontin mRNA were detected in the wall surrounding atheroma and closely
      associated with calcification. They were morphologically identified as foam cells
      and immunohistologically positive with HHF35, appearing to be derived from smooth
      muscle cells. These findings have suggested that smooth muscle cell-derived foam
      cells express osteopontin mRNA and play an important role in calcification of the
      atherosclerotic lesions.

PMID- 8254037
TI  - Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3
      genes as well as the VH4.21 gene segment.
AB  - In the current study, we wished to determine if the V regions encoding the
      naturally occurring anti-i/I Cold Agglutinins (anti-i/I CA) differ from
      pathogenic anti-i/I CA that are exclusively encoded by the VH4.21 gene. After EBV
      transformation of B lymphocytes, we generated one anti-I secreting clone from
      each of two individuals; clone 4G (individual CM, PBL) and clone Sp1 (individual
      SC, spleen). Clone 4G expresses a VH3 gene sequence that is 92% homologous to the
      germline gene WHG26. Clone Sp1 also expresses a VH3 gene that is 98% homologous
      to the fetally rearranged M85/20P1 gene. Another clone, Sp2 (anti-i specificity),
      from individual SC is 98% homologous to the germline gene VH4.21. For
      correlation, we studied anti-i/I CA fractions purified from 15 normal sera and
      found no or relatively small amounts of 9G4 (VH4.21 related idiotype) reactive
      IgM. Five cold agglutinin fractions contained large amounts of VH3-encoded IgM
      (compared to pooled normal IgM) by virtue of their binding to modified protein
      Staph A (SPA), and absorption of three CA fractions with modified SPA
      specifically removed anti-i/I binding specificity entirely. Collectively, the
      data indicate that naturally occurring anti-i/I CA may be encoded to a large
      extent by non-VH4.21-related genes, and that the VH4.21 gene is not uniquely
      required for anti-i/I specificity.

PMID- 8254038
TI  - One systemic administration of transforming growth factor-beta 1 reverses age- or
      glucocorticoid-impaired wound healing.
AB  - The role of intravenously administered recombinant human transforming growth
      factor-beta 1 (rhTGF-beta 1) on the healing of incisional wounds in rats with
      impaired healing due to age or glucocorticoid administration was investigated.
      The administration of methylprednisolone to young adult rats decreased wound
      breaking strength to 50% of normal control. Breaking strength of incisional
      wounds from 19-mo-old rats was decreased approximately 27% compared with wounds
      from normal healing young adult rats. A single intravenous administration of
      rhTGF-beta 1 (100 or 500 micrograms/kg) increased wound breaking strength from
      old rats or young adult rats with glucocorticoid-induced impaired healing to
      levels similar to normal healing control animals when determined 7 d after
      injury. Even though the circulating half-life of systemically administered rhTGF
      beta 1 is < 5 min, a sustained stimulatory effect on extracellular matrix
      secretion was evident in glucocorticoid-impaired rats when rhTGF-beta 1 was
      administered at the time of wounding, 4 h after wounding, or even 24 h before
      wounding. These observations indicate a previously unrecognized potential for the
      active form of TGF-beta 1 to profoundly influence the wound healing cascade after
      brief systemic exposure.

PMID- 8254039
TI  - Expression of parathyroid hormone-related protein in the rat glomerulus and
      tubule during recovery from renal ischemia.
AB  - Parathyroid hormone-related protein (PTHrP) is widely expressed in normal adult
      and fetal tissues, where it acts in an autocrine/paracrine fashion, stimulates
      growth and differentiation, and shares early response gene characteristics. Since
      recovery from renal injury is associated with release of local growth factors, we
      examined the expression and localization of PTHrP in normal and ischemic adult
      rat kidney. Male Sprague-Dawley rats underwent complete bilateral renal artery
      occlusion for 45 min, followed by reperfusion for 15 min, and 2, 6, 24, 48, and
      72 h. Renal PTHrP mRNA levels, when compared with sham-operated animals,
      increased twofold after ischemia, and peaked within 6 h after reperfusion. PTH
      receptor, beta-actin, and cyclophilin mRNA levels all decreased after ischemia.
      PTHrP immunohistochemical staining intensity increased in proximal tubular cells
      after ischemia, changing its location from diffusely cytoplasmic to subapical by
      24 h after reperfusion. In addition, PTHrP localized to glomerular epithelial
      cells (visceral and parietal), but not to mesangial cells. PTHrP and PTH
      stimulated proliferation two- to threefold in cultured mesangial cells. We
      conclude that PTHrP mRNA and protein production are upregulated after acute renal
      ischemic injury, that PTHrP is present in glomerulus and in both proximal and
      distal tubular cells, and that PTHrP stimulates DNA synthesis in mesangial cells.
      The precise functions of PTHrP in normal and injured kidney remain to be defined.

PMID- 8254040
TI  - Cell-matrix interactions modulate interstitial collagenase expression by human
      keratinocytes actively involved in wound healing.
AB  - We reported that interstitial collagenase is produced by keratinocytes at the
      edge of ulcers in pyogenic granuloma, and in this report, we assessed if
      production of this metalloproteinase is a common feature of the epidermal
      response in a variety of wounds. In all samples of chronic ulcers, regardless of
      etiology, and in incision wounds, collagenase mRNA, localized by in situ
      hybridization, was prominently expressed by basal keratinocytes bordering the
      sites of active re-epithelialization indicating that collagenolytic activity is a
      characteristic response of the epidermis to wounding. No expression of mRNAs for
      72- and 92-kD gelatinases or matrilysin was seen in keratinocytes, and no signal
      for any metalloproteinase was detected in normal epidermis. Immunostaining for
      type IV collagen showed that collagenase-positive keratinocytes were not in
      contact with an intact basement membrane and, unlike normal keratinocytes,
      expressed alpha 5 beta 1 receptors. These observations suggest that cell-matrix
      interactions influence collagenase expression by epidermal cells. Indeed, as
      determined by ELISA, primary cultures of human keratinocytes grown on basement
      membrane proteins (Matrigel; Collaborative Research Inc., Bedford, MA) did not
      express significant levels of collagenase, whereas cells grown on type I collagen
      produced markedly increased levels. These results suggest that migrating
      keratinocytes actively involved in re-epithelialization acquire a collagenolytic
      phenotype upon contact with the dermal matrix.

PMID- 8254041
TI  - Endothelium-dependent hyperpolarization caused by bradykinin in human coronary
      arteries.
AB  - The present study was designed to determine whether bradykinin induces
      endothelium-dependent hyperpolarization of vascular smooth muscle in human
      coronary arteries, and if so, to define the contribution of this
      hyperpolarization to endothelium-dependent relaxations. The membrane potential of
      arterial smooth muscle cells (measured by glass microelectrodes) and changes in
      isometric force were recorded in tissues from six patients undergoing heart
      transplantation. In the presence of indomethacin and NG-nitro-L-arginine (NLA),
      the membrane potential was -48.3 +/- 0.6 and -46.9 +/- 0.6 mV, in preparations
      with and without endothelium, respectively, and was not affected by treatment
      with perindoprilat, an angiotensin-converting enzyme inhibitor. In the presence
      of both indomethacin and NLA, bradykinin evoked transient and concentration
      dependent hyperpolarizations only in tissues with endothelium, which were
      augmented by perindoprilat and mimicked by the calcium ionophore A23187.
      Glibenclamide did not inhibit membrane hyperpolarization to bradykinin. In rings
      contracted with prostaglandin F2 alpha, the cumulative addition of bradykinin
      caused a concentration-dependent relaxation during contractions evoked by
      prostaglandin F2 alpha, which was not abolished by NLA and indomethacin. The
      present findings demonstrate the occurrence of endothelium-dependent
      hyperpolarization, and its contribution to endothelium-dependent relaxations, in
      the human coronary artery.

PMID- 8254042
TI  - Vasodilation of rat retinal microvessels induced by monobutyrin. Dysregulation in
      diabetes.
AB  - 1-Butyryl-glycerol (monobutyrin) is a simple lipid product of adipocytes with
      angiogenic activity. Recent studies have shown that the biosynthesis of this
      compound is tightly linked to lipolysis, a process associated with changes in
      blood flow. We now present data indicating that monobutyrin is an effective
      vasodilator of rodent blood vessels using a fluorescent retinal angiogram assay.
      The vasodilatory activity of monobutyrin is potent (ED50 = 3.3 x 10(-7) M), dose
      dependent, and stereospecific. Because diabetes represents a catabolic, lipolytic
      state with numerous vascular complications, we examined the action and regulation
      of monobutyrin in insulin-deficient diabetic rats. Serum levels of monobutyrin in
      streptozotocin-induced diabetic rats were greatly elevated compared to normal
      animals. At the same time, the retinal vessels of the diabetic animals develop a
      resistance to the vasodilatory activity of monobutyrin. These results demonstrate
      a role for monobutyrin in the control of vascular tone and suggest a possible
      involvement in the pathology of diabetes.

PMID- 8254043
TI  - The reovirus M1 gene determines the relative capacity of growth of reovirus in
      cultured bovine aortic endothelial cells.
AB  - Since blood-borne viruses often interact with endothelial cells before tissue
      invasion, the interaction between viruses and endothelial cells is likely to be
      important in viral pathogenicity. Two reovirus isolates (type 1 Lang and type 3
      Dearing) differ in their capacity to grow in cultured bovine aortic endothelial
      cells. The mammalian reoviruses have 10 double-stranded RNA gene segments in
      their genome. By using 24 reassortant viruses, observed differences in the
      capacity of different strains to grow in cultured endothelial cells were mapped
      to the M1 gene (P = 0.00019), which encodes the viral core protein mu 2. No
      differences were detected in binding or proteolytic processing of viral outer
      capsid proteins of parental virions between the two reovirus isolates. Northern
      blot analysis showed a decreased production of viral mRNA in endothelial cells
      infected with type 3 Dearing reovirus, but not type 1 Lang. Thus, we have
      identified a viral gene (the M1 gene) responsible for determining the difference
      in growth capacity of the two reovirus isolates in cultured endothelial cells.
      Reovirus is an attractive model in which to study the interaction of viruses with
      endothelial cells at a molecular genetic level.

PMID- 8254044
TI  - Glucose-induced protein kinase C activity regulates arachidonic acid release and
      eicosanoid production by cultured glomerular mesangial cells.
AB  - Changes in glomerular eicosanoid production have been implicated in the
      development of diabetes-induced glomerular hyperfiltration and glomerular
      mesangial cells (GMC) are major eicosanoid-producing cells within the glomerulus.
      However, the mechanism for the effect of diabetes mellitus on glomerular
      mesangial eicosanoid production is unknown. The present study therefore examined
      whether elevated glucose concentrations activate protein kinase C (PKC) in GMC
      and whether this PKC activation mediates an effect of elevated glucose
      concentrations to increase the release of arachidonic acid and eicosanoid
      production by GMC. The percentage of [3H]arachidonic acid release per 30 min by
      preloaded GMC monolayers was significantly increased after 3-h exposure to high
      glucose (20 mM) medium (177% vs control medium) and this increase was sustained
      after 24-h exposure to high glucose concentrations. 3-h and 24-h exposure to high
      glucose medium also increased PGE2, 6-keto-PGF1 alpha, and thromboxane (TXB2)
      production by GMC. High glucose medium (20 mM) increased PKC activity in GMC at 3
      and 24 h (168% vs control). In contrast, osmotic control media containing either
      L-glucose or mannitol did not increase arachidonic acid release, eicosanoid
      production, or PKC activity in GMC. Inhibiting glucose-induced PKC activation
      with either H-7 (50 microM) or staurosporine (1 microM) prevented glucose-induced
      increases in arachidonic acid release and eicosanoid production by GMC. These
      data demonstrate that elevated extracellular glucose concentrations directly
      increase the release of endogenous arachidonic acid and eicosanoids by GMC via
      mechanisms dependent on glucose-induced PKC activation.

PMID- 8254045
TI  - Platelet-derived growth factor inhibits bone regeneration induced by osteogenin,
      a bone morphogenetic protein, in rat craniotomy defects.
AB  - Platelet-derived growth factor (PDGF) is a potent moderator of soft tissue repair
      through induction of the inflammatory phase of repair and subsequent enhanced
      collagen deposition. We examined the effect of recombinant BB homodimer PDGF
      (rPDGF-BB) applied to rat craniotomy defects, treated with and without bovine
      osteogenin (OG), to see if bone regeneration would be stimulated. Implants
      containing 0, 20, 60, or 200 micrograms rPDGF-BB, reconstituted with insoluble
      rat collagenous bone matrix containing 0, 30, or 150 micrograms OG, were placed
      into 8-mm craniotomies. After 11 d, 21 of the 144 rats presented subcutaneous
      masses superior to the defect sites. The masses, comprised of serosanguinous
      fluid encapsulated by fibrous connective tissue, were larger and occurred more
      frequently in rats treated with 200 micrograms rPDGF-BB, and were absent in rats
      not treated with rPDGF-BB. The masses underwent resorption within 28 d after
      surgery. OG (2-256 micrograms) caused a dose-dependent increase in radiopacity
      and a marked regeneration of calcified tissue in a dose-dependent fashion within
      defect sites. However, OG-induced bone regeneration was inhibited 17-53% in the
      presence of rPDGF-BB. These results suggest that rPDGF-BB inhibited OG-induced
      bone regeneration and stimulated a soft tissue repair wound phenotype and
      response.

PMID- 8254047
TI  - Accumulation of "small dense" low density lipoproteins (LDL) in a homozygous
      patients with familial defective apolipoprotein B-100 results from heterogenous
      interaction of LDL subfractions with the LDL receptor.
AB  - The interaction of LDL and LDL subfractions from a patient homozygous for
      familial defective apoB-100 (FDB) has been studied. His LDL cholesterol ranged
      from 2.65 to 3.34 g/liter. In cultured fibroblasts, binding, internalization, and
      degradation of the patient's LDL was diminished, but not completely abolished.
      The patient's apolipoprotein E concentration was low, and the amount of
      apolipoprotein E associated with LDL was not elevated over normal. LDL were
      separated into six subfractions: LDL-1 (1.019-1.031 kg/liter), LDL-2 (1.031-1.034
      kg/liter), LDL-3 (1.034-1.037 kg/liter), LDL-4 (1.037-1.040 kg/liter), LDL-5
      (1.040-1.044 kg/liter), and LDL-6 (> 1.044 kg/liter). LDL-5 and LDL-6 selectively
      accumulated in the patient's plasma. Concentrations of LDL-1 to 3 were normal.
      The LDL receptor-mediated uptake of LDL-1 and LDL-2 could not be distinguished
      from normal LDL. LDL-3 and LDL-4 displayed reduced uptake; LDL-5 and LDL-6 were
      completely defective in binding. When apolipoprotein E-containing particles were
      removed by immunoabsorption before preparing subfractions, LDL-3 and LDL-4, but
      not LDL-1 and LDL-2, retained some receptor binding activity. We conclude that in
      FDB, LDL-1 and LDL-2 contain sufficient apolipoprotein E to warrant normal
      cellular uptake. In LDL-3 and LDL-4, the defective apoB-100 itself displays some
      receptor binding; LDL-5 and LDL-6 are inable to interact with LDL receptors and
      accumulate in plasma.

PMID- 8254046
TI  - Two novel pathogenic mitochondrial DNA mutations affecting organelle number and
      protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot?
AB  - We identified two patients with pathogenic single nucleotide changes in two
      different mitochondrial tRNA genes: the first mutation in the tRNA(Asn) gene, and
      the ninth known mutation in the tRNA(Leu(UUR)) gene. The mutation in tRNA(Asn)
      was associated with isolated ophthalmoplegia, whereas the mutation in
      tRNA(Leu(UUR)) caused a neurological syndrome resembling MERRF (myoclonus
      epilepsy and ragged-red fibers) plus optic neuropathy, retinopathy, and diabetes.
      Both mutations were heteroplasmic, with higher percentages of mutant mtDNA in
      affected tissues, and undetectable levels in maternal relatives. Analysis of
      single muscle fibers indicated that morphological and biochemical alterations
      appeared only when the proportions of mutant mtDNA exceeded 90% of the total
      cellular mtDNA pool. The high incidence of mutations in the tRNA(Leu(UUR)) gene
      suggests that this region is an "etiologic hot spot" in mitochondrial disease.

PMID- 8254048
TI  - Impairment of cardiac function and energetics in experimental renal failure.
AB  - Cardiac function and energetics in experimental renal failure in the rat (5/6
      nephrectomy) have been investigated by means of an isolated perfused working
      heart preparation and an isometric Langendorff preparation using 31P nuclear
      magnetic resonance (31P NMR). 4 wk after nephrectomy cardiac output of isolated
      hearts perfused with Krebs-Henseleit buffer was significantly lower (P < 0.0001)
      at all levels of preload and afterload in the renal failure groups than in the
      pair-fed sham operated control group. In control hearts, cardiac output increased
      with increases in perfusate calcium from 0.73 to 5.61 mmol/liter whereas uremic
      hearts failed in high calcium perfusate. Collection of 31P NMR spectra from
      hearts of renal failure and control animals during 30 min normoxic Langendorff
      perfusion showed that basal phosphocreatine was reduced by 32% to 4.7 mumol/g wet
      wt (P < 0.01) and the phosphocreatine to ATP ratio was reduced by 32% (P < 0.01)
      in uremic hearts. During low flow ischemia, there was a substantial decrease in
      phosphocreatine in the uremic hearts and an accompanying marked increase in
      release of inosine into the coronary effluent (14.9 vs 6.1 microM, P < 0.01). We
      conclude that cardiac function is impaired in experimental renal failure, in
      association with abnormal cardiac energetics and increased susceptibility to
      ischemic damage. Disordered myocardial calcium utilization may contribute to
      these derangements.

PMID- 8254049
TI  - Entry of cholera toxin into polarized human intestinal epithelial cells.
      Identification of an early brefeldin A sensitive event required for A1-peptide
      generation.
AB  - The effect of brefeldin-A (BFA), a reversible inhibitor of vesicular transport,
      on cholera toxin (CT)-induced Cl- secretion (Isc) was examined in the polarized
      human intestinal cell line, T84. Pretreatment of T84 monolayers with 5 microM BFA
      reversibly inhibited Isc in response to apical or basolateral addition of 120 nM
      CT (2.4 +/- 0.5 vs. 68 +/- 3 microA/cm2, n = 5). In contrast, BFA did not inhibit
      Isc responses to the cAMP agonist VIP (63 +/- 7 microA/cm2). BFA had no effect on
      cell surface binding and endocytosis of a functional fluorescent CT analog or on
      the dose dependency of CT induced 32P-NAD ribosylation of Gs alpha in vitro. In
      contrast, BFA completely inhibited (> 95%) the ability of T84 cells to reduce CT
      to the enzymatically active A1-peptide. BFA had to be added within the first 10
      min of CT exposure to inhibit CT-elicited Isc. The early BFA-sensitive step
      occurred before a temperature-sensitive step essential for apical CT action.
      These studies show that sequential steps are required for a biological response
      to apical CT: (a) binding to cell surfaces and rapid endocytosis; (b) early, BFA
      sensitive vesicular transport essential for reduction of the A1-peptide; and (c)
      subsequent temperature-sensitive translocation of a signal (the A1-peptide or
      possibly ADP-ribose-Gs alpha) to the basolateral domain.

PMID- 8254050
TI  - Skeletal muscle glycogenolysis is more sensitive to insulin than is glucose
      transport/phosphorylation. Relation to the insulin-mediated inhibition of hepatic
      glucose production.
AB  - The effects of minimal increments in plasma insulin concentrations on hepatic
      glucose production and glucose uptake, skeletal muscle net glycogen synthesis and
      glycogenolysis, glycogen synthase and phosphorylase activity, glucose-6-phosphate
      and uridinediphosphoglucose (UDPG) concentrations were examined in 24-h and in 6
      h fasted conscious rats. Insulin was infused for 120 min at rates of 1.5, 3, 6,
      12, 24, and 108 pmol/kg per min in 24-h fasted rats and at rates of 3, 6, 9, 12,
      36, and 108 pmol/kg per min in 6-h fasted rats while endogenous insulin release
      was inhibited by SRIF infusion and plasma glucose was maintained at the basal
      level. All rats received an infusion of [3-3H]glucose. The portion of the muscle
      glucose-6-phosphate (G6P) pool derived from net glycogenolysis was estimated from
      the ratio of specific activities of muscle UDPG and plasma glucose. Minimal
      increments in the circulating insulin levels, which did not stimulate glucose
      uptake, caused: (a) the increase in skeletal muscle glycogen synthase activity
      and the decrease in the rate of muscle glycogenolysis and in the G6P
      concentration; (b) the inhibition of hepatic glucose production. Net muscle
      glycogen synthesis was not stimulated despite submaximal activation of glycogen
      synthase, and its onset correlated with the rise in muscle G6P levels. Thus,
      insulin's inhibition of muscle glycogenolysis is the most sensitive insulin
      action on skeletal muscle and its dose-response characteristics resemble those
      for the inhibition of hepatic glucose production. These findings indicate that
      skeletal muscle glycogen synthase may play a major role in carbohydrate
      homeostasis even under postabsorptive (basal insulin) conditions and support the
      notion that insulin may exert some of its effects on the liver through an
      indirect or peripheral mechanism.

PMID- 8254051
TI  - Bence Jones proteins bind to a common peptide segment of Tamm-Horsfall
      glycoprotein to promote heterotypic aggregation.
AB  - Bence Jones proteins (BJPs) are the major pathogenic factor causing cast
      nephropathy ("myeloma kidney") by coaggregation with Tamm-Horsfall glycoprotein
      (THP). Understanding the interaction between these proteins is therefore
      important in developing treatment strategies to prevent renal failure from cast
      formation in multiple myeloma. We developed an enzyme-linked immunoassay to
      examine this phenomenon. Five different human BJPs (four kappa and one lambda
      immunoglobulin light chains) were used in this assay that demonstrated these
      proteins bound THP with different affinity. BJPs competed among themselves for
      binding to THP. The binding site was a peptide portion of THP since these
      proteins also bound deglycosylated THP. Also, one monoclonal antibody directed
      against a peptide segment of human THP prevented binding of THP to BJPs. By
      altering the conformation of THP, reducing agents decreased binding between these
      two proteins in concentration-dependent fashion. In turbidity studies, the
      monoclonal antibody that prevented binding and a reducing agent, dithiothreitol,
      decreased coaggregation. Deglycosylated THP did not coaggregate with BJPs. We
      concluded that ionic interaction between BJPs and a specific peptide binding site
      on THP promoted heterotypic coaggregation. The carbohydrate moiety of THP was
      also essential for coaggregation, perhaps by facilitating homotypic aggregation
      of THP.

PMID- 8254052
TI  - Tauroursodeoxycholic acid stimulates hepatocellular exocytosis and mobilizes
      extracellular Ca++ mechanisms defective in cholestasis.
AB  - To assess the effects of tauroursodeoxycholic acid (TUDCA) on bile excretory
      function, we examined whether TUDCA modulates vesicular exocytosis in the
      isolated perfused liver of normal rats in the presence of high (1.9 mM) or low
      (0.19 mM) extracellular Ca++ and in cholestatic rats 24 h after bile duct
      ligation. In addition, the effects of TUDCA on Ca++ homeostasis were compared in
      normal and in cholestatic hepatocytes. In the isolated perfused rat liver, TUDCA
      (25 microM) stimulated a sustained increase in the biliary excretion of
      horseradish peroxidase, a marker of the vesicular pathway, in the presence of
      high, but not low extracellular Ca++ or in the cholestatic liver. In contrast,
      TUDCA stimulated bile flow to the same extent regardless of the concentration of
      extracellular Ca++ or the presence of cholestasis. In indo-1-loaded hepatocytes,
      basal cytosolic free Ca++ ([Ca++]i) levels were not different between normal and
      cholestatic cells. However, in cholestatic cells [Ca++]i increases induced by
      TUDCA (10 microM) and its 7 alpha-OH epimer taurochenodeoxycholic acid (50
      microM) were reduced to 22% and 26%, respectively, compared to normal cells. The
      impairment of TUDCA-induced [Ca++]i increase in cholestatic cells could be
      mimicked by exposing normal cells to low extracellular Ca++ (21%) or to the Ca++
      channel blocker NiCl2 (23%). These data indicate that (a) dihydroxy bile acid
      induced Ca++ entry may be of functional importance in the regulation of
      hepatocellular vesicular exocytosis, and (b) this Ca++ entry mechanism across the
      plasma membrane is impaired in cholestatic hepatocytes. We speculate that the
      beneficial effect of ursodeoxycholic acid in cholestatic liver diseases may be
      related to the Ca+(+)-dependent stimulation of vesicular exocytosis by its
      conjugate.

PMID- 8254053
TI  - Restoration of the cAMP second messenger pathway enhances cardiac preservation
      for transplantation in a heterotopic rat model.
AB  - Current organ preservation strategies subject graft vasculature to severe hypoxia
      (PO2 approximately 20 Torr), potentially compromising vascular function and
      limiting successful transplantation. Previous work has shown that cAMP modulates
      endothelial cell (EC) antithrombogenicity, barrier function, and leukocyte/EC
      interactions, and that hypoxia suppresses EC cAMP levels. To explore the possible
      benefits of cAMP analogs/agonists in organ preservation, we used a rat
      heterotopic cardiac transplant model; dibutyryl cAMP added to preservation
      solutions was associated with a time- and dose-dependent increase in the duration
      of cold storage associated with successful graft function. Preservation was also
      enhanced by 8-bromo-cAMP, the Sp isomer of adenosine 3',5'monophosphorothioate,
      and types III (indolidan) and IV (rolipram) phosphodiesterase inhibitors. Neither
      butyrate alone nor 8-bromoadenosine were effective, and the cAMP-dependent
      protein kinase antagonist Rp isomer of adenosine 3',5'monophosphorothioate
      prevented preservation enhancement induced by 8-bromo-cAMP. Grafts stored with
      dibutyryl cAMP demonstrated a 5.5-fold increase in blood flow and a 3.2-fold
      decreased neutrophil infiltration after transplantation. To explore the role of
      cAMP in another cell type critical for vascular homeostasis, vascular smooth
      muscle cells were subjected to hypoxia, causing a time-dependent decline in cAMP
      levels. Although adenylate cyclase activity was unchanged, diminished oxygen
      tensions were associated with enhanced phosphodiesterase activity (59 and 30%
      increase in soluble types III and IV activity, respectively). These data suggest
      that hypoxia or graft ischemia disrupt vascular homeostasis, at least in part, by
      perturbing the cAMP second messenger pathway. Supplementation of this pathway
      provides a new approach for enhancing cardiac preservation, promoting myocardial
      function, and maintaining vascular homeostatic properties.

PMID- 8254054
TI  - Mechanical strain and collagen potentiate mitogenic activity of angiotensin II in
      rat vascular smooth muscle cells.
AB  - The effects of extracellular matrix proteins and mechanical strain on the
      mitogenic activity of angiotensins I and II (AI and AII) were examined in
      cultured rat vascular smooth muscle (VSM) cells. VSM cells on various
      extracellular matrices were exposed to AII (1 microM) for 48 h. On plastic, AII
      induced only a 1.6-fold increase in [3H]thymidine incorporation, but on
      fibronectin- or type I collagen-coated plastic, the response to AII was enhanced
      from two- to fourfold. On a type I collagen-coated silicone elastomer, to which
      mechanical strain was applied, [3H]thymidine incorporation dramatically increased
      to a maximum of 53-fold. Dup 753 (10(-5) M) blocked the AII-induced increase in
      DNA synthesis. AI also increased DNA synthesis in VSM cells, and this response
      was also enhanced by mechanical strain. Mitogenic activity of AI was blocked by
      ramiprilat (10(-5) M), indicating that its mitogenic activity was via conversion
      to AII. The synergy between AII and strain was completely eliminated by
      neutralizing antibodies to PDGF AB (3 micrograms/ml). Furthermore, the mitogenic
      effect of AII in unstrained cells was also synergistic with submaximal
      concentrations of PDGF AB (1 ng/ml). Thus, the synergy between AII and mechanical
      strain probably results from synergism between AII and PDGF secreted in response
      to strain.

PMID- 8254055
TI  - Upregulated expression and function of integrin adhesive receptors in systemic
      lupus erythematosus patients with vasculitis.
AB  - Upregulation of integrin adhesive receptors has been implicated in various
      pathological conditions. We examined expression and function of integrin adhesive
      receptors on peripheral blood lymphocytes from patients with systemic lupus
      erythematosus (SLE), particularly those with the complication of vasculitis, and
      found that VLA-4 and LFA-1 expression was increased in SLE patients with
      vasculitis, while LFA-1 but not VLA-4 expression was increased in those without
      vasculitis. These results suggested a role of VLA-4 in the pathogenesis of
      vasculitis in SLE. Functional studies further demonstrated that adhesion to
      cytokine-activated human umbilical cord vein endothelial cells and to the CS-1
      alternatively spliced domain of fibronectin was significantly increased in SLE
      patients with vasculitis. Analysis of the functional epitopes on the alpha 4
      chain demonstrated that antigen densities of all the functional epitopes were
      increased in those with vasculitis, indicating that the increased expression of
      VLA-4 resulted from the increased number of VLA-4 molecules, and was not
      secondary to an increase in one particular functional epitope.
      Immunoprecipitation studies further support these results. Interestingly, high
      molecular weight bands associated with VLA-4 were observed in about half of the
      SLE patients with vasculitis. These results introduce a possibility that
      upregulation of integrin adhesive receptors has a potential role in the
      pathogenesis of vasculitis in SLE.

PMID- 8254056
TI  - Endothelial cell Ca2+ increases upon tumor cell contact and modulates cell-cell
      adhesion.
AB  - The signal transduction mechanisms involved in tumor cell adhesion to endothelial
      cells are still largely undefined. The effect of metastatic murine melanoma cell
      and human prostate carcinoma cell contact on cytosolic [Ca2+] of bovine artery
      endothelial cells was examined in indo-1-loaded endothelial cell monolayers. A
      rapid increase in endothelial cell [Ca2+] occurred on contact with tumor cells,
      but not on contact with 8-microns inert beads. A similar increase in endothelial
      cell [Ca2+] was observed with human neutrophils or monocyte-like lymphoma cells,
      but not with endothelial cells, red blood cells, and melanoma cell-conditioned
      medium. The increase in endothelial cell [Ca2+] was not inhibited by
      extracellular Ca2+ removal. In contrast, endothelial cell pretreatment with
      thapsigargin, which releases endoplasmic reticulum Ca2+ into the cytosol and
      depletes this Ca2+ store site, abolished the cytosolic [Ca2+] rise upon melanoma
      cell contact. Endothelial cell pretreatment with the membrane-permeant form of
      the Ca2+ chelator bis-(O-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid blocked
      the increase in cytosolic [Ca2+]. Under static and dynamic flow conditions (0.46
      dyn/cm2) bis-(O-aminophenoxyl)ethane-N,N,N',N'-tetraacetic acid pretreatment of
      bovine pulmonary artery endothelial cell monolayers inhibited melanoma cell
      adhesion to the endothelial cells. Thus, tumor cell contact with endothelial
      cells induces a rapid Ca2+ release from endothelial intracellular stores, which
      has a functional role in enhancing cell-cell adhesion.

PMID- 8254057
TI  - Transgenic mice expressing high plasma concentrations of human apolipoprotein
      B100 and lipoprotein(a).
AB  - The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those
      classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants,
      beta-VLDL, LDL, oxidized LDL, and Lp(a)]. Here we describe the development of
      transgenic mice expressing high levels of human apo-B48 and apo-B100. A 79.5-kb
      human genomic DNA fragment containing the entire human apo-B gene was isolated
      from a P1 bacteriophage library and microinjected into fertilized mouse eggs. 16
      transgenic founders expressing human apo-B were generated, and the animals with
      the highest expression had plasma apo-B100 levels nearly as high as those of
      normolipidemic humans (approximately 50 mg/dl). The human apo-B100 in transgenic
      mouse plasma was present largely in lipoproteins of the LDL class as shown by
      agarose gel electrophoresis, chromatography on a Superose 6 column, and density
      gradient ultracentrifugation. When the human apo-B transgenic founders were
      crossed with transgenic mice expressing human apo(a), the offspring that
      expressed both transgenes had high plasma levels of human Lp(a). Both the human
      apo-B and Lp(a) transgenic mice will be valuable resources for studying apo-B
      metabolism and the role of apo-B and Lp(a) in atherosclerosis.

PMID- 8254058
TI  - Nonenzymatic glycosylation-induced modifications of intact bovine kidney tubular
      basement membrane.
AB  - We examined structural changes in bovine kidney tubular basement membrane (TBM)
      following in vitro nonenzymatic glycosylation (NEG). Isolated TBM was incubated
      for 2 wk at 37 degrees C in the absence of sugar or in the presence of either
      glucose or ribitol under conditions that minimized degradation and oxidative
      damage. NEG and crosslink formation in glycated TBM were confirmed by decreased
      solubility, increased amounts of low mobility material by SDS-PAGE, and increased
      specific fluorescence compared to controls. Morphological analysis using high
      resolution, low voltage scanning electron microscopy (LV-SEM) revealed a complex
      three-dimensional meshwork of interconnecting strands with intervening openings.
      Glycated TBM underwent distinct morphological changes, including a 58% increase
      in the amount of image surface area occupied by openings. This was due to an
      apparent increase in the number of large openings (diameters > 12.5 nm), whereas
      the number of small openings (diameters < 12.5 nm) remained unchanged. These
      findings corroborate earlier physiological studies, which established that the
      loss of glomerular permselectivity seen in patients with diabetic nephropathy is
      due to the formation of large pores in the kidney filtration barrier of which the
      BM is a major component. We conclude that NEG and crosslink formation among BM
      components lead to modifications of BM ultrastructure, which could play a role in
      loss of barrier function in diabetic microangiopathy and nephropathy.

PMID- 8254059
TI  - Immunologic changes occurring at kindergarten entry predict respiratory illnesses
      after the Loma Prieta earthquake.
AB  - Previous studies in adult populations have demonstrated alterations in immune
      function after psychologically stressful events, and pediatric research has shown
      significant associations between stress and various childhood morbidities.
      However, no previous work has examined stress-related immune changes in children
      and subsequent illness experience. Twenty children were enrolled in a study on
      immunologic changes after kindergarten entry and their prospective relationship
      to respiratory illness (RI) experience. Midway through a 12-week RI data
      collection period, the October 17, 1989 Loma Prieta earthquake occurred. The
      timing of this event created a natural experiment enabling us to study possible
      associations between immunologic changes at kindergarten entry, the intensity of
      earthquake-related stress for children and parents, and changes in RI incidence
      over the 6 weeks after the earthquake. Immunologic changes were measured using
      helper (CD4+)-suppressor (CD8+) cell ratios, lymphocyte responses to pokeweed
      mitogen, and type-specific antibody responses to Pneumovax, in blood sampled 1
      week before and 1 week after school entry. RI incidence was assessed using home
      health diaries and telephone interviews completed every 2 weeks. RIs per child
      varied from none to six. Six children showed an increase in RI incidence after
      the earthquake; five experienced a decline. Changes in helper-suppressor cell
      ratios and pokeweed mitogen response predicted changes in RI incidence in the
      postearthquake period (r = .43, .46; p < .05). Children showing upregulation of
      immune parameters at school entry sustained a significant increase in RI
      incidence after the earthquake.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254060
TI  - The effects of age and gender on reading achievement: implications for pediatric
      counseling.
AB  - The hypothesis that age of school entrance and gender interact to affect academic
      achievement was tested on three samples of children at the end of 1st (n = 1215),
      2nd (n = 1141), and 3rd grade (n = 1037). Multiple regressions of age, gender,
      and their interaction on reading achievement resulted in significant effects of
      age for each sample. However, these variables together accounted for less than 1%
      of the variability in reading scores at each grade. There was a significant
      interaction between age and gender for the 3rd grade sample. Separate gender
      analyses of variance by age class revealed that girls who were 6 years or older
      at the time of entrance achieved significantly lower than middle-entrance-age or
      younger girls. Contrary to popular belief, there were no significant age class
      effects for boys. These findings indicate that significantly more attention
      should be focused on the specific skills that children bring to the learning
      process than on their age and gender in assessing readiness. Implications for
      pediatric counseling are discussed.

PMID- 8254061
TI  - Screening mothers of young children for substance abuse.
AB  - Pediatricians have been urged to screen for parental substance abuse, but few
      screening instruments have been tested for mothers. We compared six screening
      questions for maternal alcohol and drug abuse with the Michigan Alcoholism
      Screening Test (MAST) and the Drug Abuse Screening Test (DAST). Questionnaires
      were completed by 507 mothers; most were Caucasian (78%) and married (75%).
      Eighteen percent were positive on the MAST, and 3% were positive on the DAST. The
      screening questions for drinking had a 90% sensitivity compared with the MAST;
      the questions about drug use had a sensitivity of 88% compared with the DAST. The
      MAST detected only 25% of mothers who reported physiologic tolerance to alcohol
      and 32% of those who reported binge drinking; the DAST failed to detect any
      mothers who reported using drugs in the previous 24 hours. The six screening
      questions about alcohol and drug use had good sensitivity, detected potential
      drinking problems and drug abuse missed by the MAST and DAST, and can be
      incorporated easily into a comprehensive psychosocial questionnaire.

PMID- 8254062
TI  - Pediatric clinical assessment of mother-child interaction: concurrent and
      predictive validity.
AB  - This study examines whether clinical assessments of mother-infant interactions
      collected at 8-month health supervision visits are associated with standardized
      measures of the home environment and mother-child interaction collected at later
      dates in other settings, and whether these clinical assessments are associated
      with the child's future developmental and behavioral status. The observation
      component of the Pediatric Review of Children's Environmental Support and
      Stimulation (PROCESS) was collected on 46 consecutive mother-infant pairs during
      an 8-month health supervision visit. The Home Observation Measurement of
      Environment (HOME) Inventory was collected on these infants' families at 12 and
      36 months of age, and mother-child interaction was assessed in a laboratory
      setting at 30 months. The Bayley Scales of Infant Development were collected at
      12 and 24 months, and the Stanford Binet Intelligence Test and the Achenbach
      Child Behavior Checklist were collected at 36 months of age. The 8-month clinical
      ratings were strongly associated with the measures of the home environment and
      mother-child interaction and with child developmental and behavioral problem
      status at 36 months. These findings attest to the power and usefulness of
      systematic observations of maternal behavior by the clinician during health
      supervision visits.

PMID- 8254063
TI  - Massage effects on cocaine-exposed preterm neonates.
AB  - Thirty preterm cocaine-exposed preterm neonates (mean gestational age 30 wks,
      mean birth weight = 1212 g, mean intensive care unit duration = 18 days) were
      randomly assigned to a massage therapy or a control group as soon as they were
      considered medically stable. Group assignment was based on a random
      stratification of gestational age, birth weight, intensive care unit duration,
      and entry weight into the study. The treatment group (N = 15) received massages
      for three 15-minute periods 3 consecutive hours for a 10-day period. Findings
      suggested that the massaged infants (1) averaged 28% greater weight gain per day
      (33 vs 26 g) although the groups did not differ in intake (calories or volume),
      (2) showed significantly fewer postnatal complications and stress behaviors than
      did control infants, and (3) demonstrated more mature motor behaviors on the
      Brazelton examination at the end of the 10-day study period.

PMID- 8254064
TI  - The neurocognitive phenotype of female carriers of fragile X: additional evidence
      for specificity.
AB  - The specificity of the neurocognitive profile among women with the fragile X
      gene, in relation to cytogenetic expression, was examined among 22 women with >
      or = 2% expression, 35 0% obligate carriers, and 60 controls. Measures were
      obtained for intellectual ability; achievement; and verbal, nonverbal, memory,
      and executive functions. Findings show that no group consistently demonstrated
      global deficits in the verbal, nonverbal or memory domains. In contrast, even
      when controlling for the effects of IQ, the expressing women exhibited (1)
      deficits on measures of executive function, (2) deficits in measures of attention
      and visual-spatial skills, and (3) enhanced performance on verbal, but not
      figural, memory. No deficits were seen among obligate carriers. This study
      supports the notion that executive function deficits and/or visual-spatial skills
      may account for the behavioral and cognitive manifestations of fragile X.

PMID- 8254065
TI  - Behavioral problems among twins.
AB  - Despite the frequency of multiple births, little information is available to
      assist parents and health professionals in the identification and management of
      behavior problems in multiple-birth siblings. Three case reports are presented
      that describe quarreling, aggression, and feeding problems among twins. To
      develop intervention strategies most appropriate for the problem behavior, it is
      important to determine whether (1) parents are able to effectively implement the
      intervention strategy, (2) behavior is isolated to one sibling, and (3) different
      reasons are responsible for similar behavior in siblings. Structured observations
      were used to determine whether the undesired behavior occurred to escape
      nonpreferred activities, gain access to preferred activities, or obtain parental
      attention. The cases provide a framework to facilitate the identification and
      management of common behavior problems occurring among multiple-birth siblings.

PMID- 8254066
TI  - Screening for behavioral and emotional problems in primary care pediatrics.
AB  - Case identification indexes based on the mother-completed Missouri Children's
      Behavior Checklist (MCBC) were compared with pediatrician identification of
      behavioral and emotional problems in 41 children seen for well-child
      examinations. Case identification indexes also were examined as a function of
      child gender and age and maternal education. The criterion was presence of DSM
      III diagnoses determined through Child Assessment Schedule interviews of child or
      mother. The MCBC yielded better case identification indexes and improvements in
      both overidentification and underidentification rates. Pediatrician
      identification indexes were directly related to maternal education and MCBC
      identification indexes were inversely related to child age. The findings indicate
      the necessity for including child report, as well as mother report, in screening
      procedures that are incorporated into primary care pediatric practice.

PMID- 8254067
TI  - Classification of suicidal and nonsuicidal outpatients: a cluster-analytic
      approach.
AB  - The revised Beck Depression Inventory (BDI), Hopelessness Scale (BHS), Anxiety
      Inventory (BAI), and Scale for Suicide Ideation (SSI) were administered to 1,172
      outpatients diagnosed with mixed psychiatric disorders. The SSI then was used to
      classify the patients into 127 (10.8%) suicide ideators and 1,045 (89.2%)
      nonideators. Both agglomerative-hierarchical and nonhierarchical cluster analyses
      then were employed to identify three types of nonideators, who represented
      anxious depressed, hopeless depressed, and below-average overall symptomatology,
      and four types of ideators, who reflected hopeless, anxious depressed, severely
      suicidal, and below-average overall symptomatology. Implications of these
      classification systems for describing psychopathology were discussed.

PMID- 8254068
TI  - Depressive mood states and their cognitive and personality correlates in college
      students: they improve over time.
AB  - About 30% of 171 college student respondents reported at least mild dysphoria.
      Depressed mood states were associated with dysfunctional attitudes and self
      esteem problems, but not with gender or self-reported problem-solving ability.
      Findings about sex role orientation were mixed. The freshmen reported the highest
      levels of dysphoria, problem-solving difficulties, and dysfunctional attitudes,
      but there appeared to be consistent, gradual improvements, such that by the
      senior year students reported significantly less dysphoria. However, a 2-month
      follow-up found no significant changes in these areas, which suggests that the
      observed improvements may occur more gradually or may be an artifact of selective
      attrition from college. Implications of the results and directions for future
      research were discussed.

PMID- 8254069
TI  - An empirical typology of seriously and persistently mentally ill patients using
      symptom and social functioning factors.
AB  - This study generated an empirical, statistically based typology that used both
      symptom data and social functioning dimensions to define subtypes of seriously
      mentally ill patients. The intent of using social functioning information was to
      explore the degree to which it improves clinicians' understanding of and
      treatment planning for diverse subgroups of patients. Social functioning
      dimensions and symptom data collected on a group of SPMI (seriously and
      persistently mentally ill) patients were factor analyzed and then submitted to a
      cluster analysis that yielded five meaningful patient subtypes. Demonstrations of
      the usefulness of this classification included significant subgroup differences
      on clinically important external variables, including needs for specific types of
      treatment and service consumption. For comparison purposes, the failure of the
      DSM-III diagnostic classification to distinguish patients on the clinically
      relevant criteria also was demonstrated.

PMID- 8254070
TI  - Measurement strategies in social support: a descriptive review of the literature.
AB  - Social support literature has been criticized for lacking methodological clarity.
      The purpose of this study was to conduct a systematic descriptive review of the
      social support literature, outline measurement problems, identify the nature of
      assessment inadequacies, and provide recommendations for the future. Two-hundred
      sixty-two empirically based articles published between 1980 and 1987 were
      reviewed comprehensively. Information about social support measurement and sample
      characteristics was obtained. A system was designed to organize the data on
      sample characteristics, type of instrument, source of support assessed, and
      category of support measured. The social support literature also was described
      from a methodological perspective, and several trends were identified.
      Conclusions about conceptual maturity, a priori biases, measurement of network
      utilization, and social support sources are discussed.

PMID- 8254071
TI  - Personality and bulimic symptomatology.
AB  - This study examined the relationship between bulimic symptomatology as measured
      by scores on the BULIT-R and personality characteristics based on the EPQ-R in a
      nonclinical sample of 166 female college students. A relationship was obtained
      between Neuroticism, Addictiveness, and scores on the BULIT-R.

PMID- 8254072
TI  - Effects of positive and negative reinforcement on daily living skills in chronic
      psychiatric patients in community residences.
AB  - The effects of contingent positive and negative reinforcement on adaptive
      behavior and mood were examined in a sample of 36 chronic, psychiatric
      outpatients. Group 1 received contingent positive token reinforcement to improve
      daily living skills, group 2 received a negative reinforcement procedure based on
      removal of free-tokens, and group 3 was a no-treatment control. Subjects were
      assessed via a weekly daily living checklist and were pre- and posttested on the
      Profile of Mood States (POMS). Significant differences were found between the
      control and treatment groups on both total activities of daily living and among
      five individual targeted behaviors. Mood states did not differ among the groups,
      which indicates benign effects of negative reinforcement. The findings of this
      study are relevant to the treatment of the serious and persistently mentally ill.

PMID- 8254073
TI  - NEO-PI profiles in PTSD as a function of trauma level.
AB  - One hundred Vietnam veterans with combat-related PTSD were administered the NEO
      Personality Inventory (NEO-PI) and the Combat Exposure Scale and were sorted into
      three groups based on trauma exposure level. Results indicate no significant
      differences among the personality profiles of the three trauma-exposed groups. A
      normative NEO-PI profile for persons diagnosed with combat-related PTSD is
      presented, characterized by an extremely high Neuroticism score (T > 75) and an
      extremely low Agreeableness score (T < 25).

PMID- 8254074
TI  - Personal and family stress in individuals with diabetes and vision loss.
AB  - The intrapersonal distress and the impact of diabetes and vision impairment on
      marital functioning were assessed. Significant degrees of intrapersonal distress
      were demonstrated by the Beck Depression Inventory, Rosenberg Self-Esteem Scale,
      and Rand Mental Health Index. Family functioning as assessed by the Family
      Assessment Device was significantly compromised. Vision impairment was a major
      stressor in the spousal relationship. Of 18 subjects who had been involved in a
      committed relationship at the onset of vision impairment, 9 had separated.
      Separation occurred at a mean of 1.6 years after the vision impairment. Totally
      blind individuals were at greater risk for separation than those who were
      legally, but not totally, blind. Psychological intervention was a limited
      benefit. Studies are necessary to identify the appropriate timing for further
      interventions.

PMID- 8254075
TI  - Factor structure of the Chinese version of the General Health Questionnaire (GHO
      30): a confirmatory factor analysis.
AB  - The factor structure of responses to the Chinese version of the General Health
      Questionnaire (CGHQ-30) in a sample of 2,150 Chinese secondary school students
      was examined using the LISREL approach to confirmatory factor analysis. The
      results showed that while a five-factor model (Anxiety, Depression, Inadequate
      Coping, Social Dysfunctioning and Sleep Disturbances) was able to fit the data, a
      higher-order factor model with five primary factors (Anxiety, Depression,
      Inadequate Coping, Social Dysfunctioning and Sleep Disturbances) and a second
      order factor (General Psychopathology) was found to be a more parsimonious model.
      The present findings are discussed with reference to the controversies that
      surround the dimensionality of the General Health Questionnaire.

PMID- 8254076
TI  - French-language validation of the DACL and MAACL-R.
AB  - The objective of this methodological pilot study was to make a contribution to
      the French-language validation of the Depressive Adjective Check List (DACL) Set
      2 of Forms, E, F, G trait version (Lubin, 1981) and to that of the Multiple
      Affect Adjective Check List (MAACL-R; Zuckerman & Lubin, 1985). The importance of
      the study was to validate the French-language translation of these instruments to
      assess nonclinical depression or dysphoria and affect in two French- and English
      speaking convenience sample groups. The Check Lists were administered to 183
      Canadian subjects 60 years of age and over of both sexes from rural areas in the
      provinces of Quebec and Ontario, Canada. In order to ensure that the words chosen
      carried the same connotation as in the English language, a translation
      retranslation technique was used. The data collected from this study suggest that
      the DACL Form G would be most valid to use with either language and/or site in
      the protocol for future studies.

PMID- 8254077
TI  - Diagnostic efficiency of the Depression Adjective Check Lists.
AB  - The diagnostic efficiency of the trait version of the Depression Adjective Check
      Lists (DACL) was studied in a two-phase investigation that involved two
      psychiatric patient samples (N = 308 and N = 67). Cutting scores developed on the
      first sample were cross-validated successfully on the second sample. In addition,
      the DACL compared favorably in diagnostic efficiency with the Beck Depression
      Inventory, the MMPI-D scale, and a Self-rating Depression scale.

PMID- 8254078
TI  - The Multi-Attitude Suicide Tendency Scale: psychometric characteristics in an
      American sample.
AB  - The Multi-Attitude Suicide Tendency Scale (MAST) was designed to assess suicidal
      tendencies in youth. This 30-item scale has four types of attitudes: attraction
      to life, repulsion by life, attraction to death, and repulsion by death.
      Normative, factor structure, and psychometric data were investigated with
      American youth with a range of suicidal ideations and behaviors. The reported
      factor structure was replicated with American youths. In addition, all four
      factor scales showed good reliability estimates. Finally, the relationships among
      the MAST factors and measures of suicidal behavior and ideation, social
      desirability, and general psychopathology were examined.

PMID- 8254079
TI  - The MAPI as a treatment outcome measure for adolescent inpatients.
AB  - The Millon Adolescent Personality Inventory (MAPI; Millon, Green, & Meagher,
      1982) was administered at admission and discharge to 215 hospitalized
      adolescents. Significant mean score differences were found for both internalizing
      (affective disorder) and externalizing (disruptive behavior disorder)
      adolescents. Consistent with theory, internalizing adolescents reported
      significantly greater distress at both admission and discharge than externalizing
      adolescents. Finally, test-retest reliability coefficients were somewhat lower
      than those reported previously (Millon et al., 1982) for hospitalized
      adolescents.

PMID- 8254080
TI  - Discriminating neuropsychological sequelae of head injury from alcohol-abuse
      induced deficits: a review and analysis.
AB  - Alcohol abuse is linked strongly with neuropsychological deficits that may
      resemble deficits seen in head-injured individuals. Heavy daily drinking appears
      more damaging than episodic abusive consumption. Cognitive deficits associated
      with alcohol include abstraction, perceptuospatial, and problem-solving skills.
      Verbal abilities are spared. For alcoholics younger than 40, abstinence is
      associated with improved functioning. For those over 40, deficits may be
      permanent. Intelligence tests are unlikely to pick up alcohol-induced deficits.
      Points for neuropsychologists to consider in differentiating between head injury
      and alcohol-induced deficits include abstinence from drinking prior to testing,
      intactness of remote memory and verbal functions, and changes in tolerance for
      alcohol.

PMID- 8254081
TI  - Is the WAIS-R an acceptable test for the elderly? Opinions of examinees 75 years
      and older.
AB  - Two hundred twenty-four healthy volunteers, 75 years of age and older (M = 80.67
      years; SD = 4.99), completed the WAIS-R and a post WAIS-R questionnaire. The
      questionnaire gathered information about the subjects' perceptions of the
      Wechsler Scale across five categories. The vast majority of subjects (over 92%)
      experienced the WAIS-R as interesting, challenging, motivating, and within their
      endurance. Only two subtests were rated negatively; Picture Arrangement and Block
      Design were experienced as tricky by 17% and 22% of the subjects, respectively.
      There were no significant differences on IQ and subtest scores between subjects
      who perceived the WAIS-R in a negative manner and those who viewed it positively.

PMID- 8254082
TI  - The residual cognitive competence of elderly females.
AB  - Factors described by Horn as affected by aging were hypothesized to
      physiologically define functional intelligence. Fifty female volunteers, who
      ranged in age from 68 to 98, were grouped as either Independent or Partially
      Dependent. Duke Activity Questionnaires validated group placement. Tasks derived
      from the Horn factors of attention, memory, and reasoning, as well as the Mini
      Mental State and the WAIS-R Similarities and Digits Forward and Backward,
      assessed cognitive status. The tasks were more often sensitive to increased
      dependence than to age and generally supported the nomination of Horn's factors
      to identify "biological" intelligence. An unusual finding, low to negative
      correlations between educational and cognitive skills, was cited as relevant
      evidence of fluid loss.

PMID- 8254083
TI  - Cognitive control differences in violent juvenile inpatients.
AB  - A stepwise discriminant analysis was used on a calibration sample (n = 135) of
      dangerous and nondangerous juvenile inpatients to determine which demographic,
      psychosocial, and cognitive variables best distinguished the violent inpatients.
      The resulting statistical model was cross-validated on the remainder of the
      sample (n = 123). Results show that the violent inpatients were more likely to be
      younger males whose family had a history of criminal behavior and extensive
      family discord. Moreover, the cognitive variables showed that violent inpatients
      showed differences in attention and memory, especially when they were processing
      aggressive stimuli. Results are discussed in terms of the potential ability of
      cognitive psychology to adopt an ecological perspective and to contribute to
      forensic assessment.

PMID- 8254084
TI  - The hierarchical factor structure of the WAIS-R for alcoholic adults.
AB  - A Wherry (1984) hierarchical factor solution was obtained on the WAIS-R subtest
      intercorrelations for 108 alcoholic adults. An ability arrangement consistent
      with Vernon's (1950) structure-of-intellect paradigm was found. This ability
      hierarchy consisted of a strong general intelligence (g) factor defined by all 11
      subtests, which accounted for 49% of the variance. The primary level of the
      ability hierarchy consisted of spatial-perceptual-mechanical (k:m), Freedom from
      Distractibility (FD), and Verbal Comprehension (VC) factors. Those respective
      factors accounted for 86%, 4%, and 3% of the total subtest variance.

PMID- 8254085
TI  - Use of histomorphometry in the assessment of fatal vertebral artery dissection.
AB  - AIM: To assess morphometrically the structural changes, which occur with ageing,
      along the length of the vertebral artery. METHODS: A series of 36 vessels were
      removed at necropsy from subjects aged between 9 months and 86 years. Image
      analysis was used to measure the medial width, the circumference, the intimal:
      medial area ratio and the adventitial: medial area ratio along each artery. The
      artery from a case of fatal vertebral artery dissection, which occurred after a
      game of cricket and then chiropractic neck manipulation, was also examined in the
      same manner. The proteoglycan accumulation in the media was quantified using an
      eyepiece graticule. RESULTS: The vertebral arteries were, on average, larger
      around the origin of the vessel from the subclavian artery, and the adventitia
      were relatively thicker at this point, and also after piercing the dura mater.
      The media were much thinner within the intracranial segment and pronounced
      intimal thickening occurred with increasing age. The dissected artery showed
      undoubtable pre-existent structural abnormalities, in the form of massive
      proteoglycan accumulation, which predisposes an artery to dissection.
      CONCLUSIONS: These data should help pathologists faced with the task of assessing
      the underlying structural integrity of the vessel wall in cases of vertebral
      artery injury.

PMID- 8254086
TI  - Epidermal growth factor receptor immunohistochemistry in different histological
      types of infiltrating breast carcinoma.
AB  - AIMS: To determine the immunohistochemical expression of epidermal growth factor
      receptor (EGF-R) in high grade, intermediate, and low grade tumours. METHODS:
      Specimens from 931 breast carcinomas were partly formalin fixed and paraffin wax
      embedded, to classify cases, and partly frozen in liquid nitrogen, cryostat
      sectioned, and immunostained using two monoclonal antibodies from clone 455 and
      528 to demonstrate EGF-R positive cells. An avidin-biotin complex and peroxidase
      method was used after incubation with biotinylated anti-mouse antibody; colour
      was developed using a diaiminobenzidine solution. RESULTS: Low grade carcinomas
      seldom expressed EGF-R (n = 3) compared with 106 high grade infiltrating ductal
      carcinomas: EGF-R positive cases were much less common in infiltrating lobular
      than in infiltrating ductal carcinoma. Medullary carcinomas did not differ from
      infiltrating ductal carcinomas. CONCLUSIONS: The very low incidence of EGF-R
      positive cases in the "special type" group of breast carcinomas with a good
      prognosis is in line with the absence of the homologous c-erbB-2 and p53
      oncoproteins, and the rarity of highly proliferating and oestrogen/progesterone
      negative cases. EGF-R expression in infiltrating lobular carcinoma was in keeping
      with the intermediate behaviour of this kind of tumour. EGF-R expression in cases
      of pure medullary carcinoma is the same as that of high grade tumours.

PMID- 8254087
TI  - Effect of tumour associated tissue eosinophilia on survival of women with stage
      IB carcinoma of the uterine cervix.
AB  - AIMS: To examine the survival of a group of women with stage IB invasive
      carcinoma of the uterine cervix, divided according to the expression of tumour
      associated tissue eosinophilia (TATE). METHODS: Histological material from 81
      women with stage IB squamous and adenosquamous cervical carcinomas before
      radiotherapy was assessed for the extent of tissue stromal eosinophilia,
      quantified using antibodies to human major basic protein. RESULTS: Twenty eight
      (38%) of the cases demonstrated TATE of over 30 eosinophils/mm2, with 12 (16%)
      having greater than 100 eosinophils/mm2. Eleven women in the series developed
      distant spread or recurrent pelvic disease, this group having a stromal
      eosinophil density significantly less (13.8/mm2) than the remainder (69.9/mm2) (p
      = 0.03). The actuarial five year survival rate for women with a tumour eosinophil
      density over 30/mm2 was 92% compared with 70% with a density under 30 mm2, with a
      significant difference in the survival curves for these two groups (p = 0.03).
      CONCLUSIONS: As a univariate parameter, a tumour associated tissue eosinophilia
      of at least modest proportions is associated with statistically improved survival
      in women with stage IB cervical carcinomas.

PMID- 8254088
TI  - PCR analysis of the upstream regulatory region of human papillomavirus genomes in
      cervical intraepithelial neoplasia and cervical carcinoma.
AB  - AIMS: To test whether human papillomavirus (HPV) variants with large scale
      sequence alterations to the upstream regulatory region are present in cervical
      intraepithelial neoplasias (CIN) and cervical carcinomas. METHODS: New PCR based
      assays were designed specifically to detect large scale insertion/deletion
      alterations in the upstream regulatory region of HPV 16 and 18. The assays were
      applied to 24 cases of CIN and 34 cases of cervical carcinoma previously shown to
      contain these two high risk HPV types. RESULTS: No large scale sequence
      alterations were found in any of the HPV containing CIN or carcinomas.
      CONCLUSIONS: These negative findings suggest that major upstream regulatory
      region variants of HPV 16 and 18 do not contribute to most cervical neoplasms.

PMID- 8254089
TI  - Malignant transformation of osteoblastoma: study using image analysis
      microdensitometry.
AB  - AIM: To determine if the malignant transformation, as perceived histologically,
      in a case of osteoblastoma from the right femur, was also expressed as a
      quantitative change in nuclear DNA during tumour progression over five months.
      METHODS: Nuclear DNA microdensitometry by computer image analysis was used to
      acquire relative DNA distribution patterns. Tissue had been removed on four
      separate occasions from a lesion in the right femur of an 18 year old man.
      Retrospective DNA analysis was performed on formalin fixed, paraffin wax-embedded
      tissue. RESULTS: The DNA profile of the initial biopsy specimen, which was
      histologically diagnosed as osteoblastoma, was euploid with a near diploid (2c)
      modal DNA. The second biopsy specimen taken one month later also resembled
      osteoblastoma but showed an aneuploid DNA profile with a diploid modal DNA and
      some nuclei with ploidy greater than 5c. The third biopsy specimen taken four
      months later showed histological evidence of osteosarcoma and a near pentaploid
      (5c) modal DNA with large number of nuclei exceeding 5c. CONCLUSIONS: DNA
      microdensitometry confirmed the initial and final diagnosis. The technique also
      seems to be capable of detecting aneuploidy before malignancy is morphologically
      evident.

PMID- 8254090
TI  - Sea blue histiocytosis: a common abnormality of the bone marrow in
      myelodysplastic syndromes.
AB  - AIMS: To determine whether myelodysplastic syndromes (MDS) are associated with
      sea blue histiocytosis in the bone marrow. METHODS: A retrospective review of
      bone marrow aspirates from 35 patients presenting consecutively with MDS and from
      20 patients with each of the following: normal marrow appearance (routine staging
      for non-Hodgkin's lymphoma), polycythaemia rubra vera, immune thrombocytopenic
      purpura (ITP), chronic myeloid leukaemia (CML) in chronic phase. RESULTS: Sea
      blue histiocytes were present in the marrow in 12 of 35 cases of MDS and occurred
      in large numbers in three of these cases. Sea blue histiocytes varied in the
      degree of cytoplasmic granularity and some cells were intermediate in appearance
      between classic sea blue histiocytes and pseudo-Gaucher cells. Sea blue
      histiocyte granules additionally stained positively with Sudan black and periodic
      acid schiff. Sea blue histiocytes occurred only in the presence of marrow
      hypercellularity. Their presence did not correlate with FAB subtype, degree of
      dyserythropoeisis, or megakaryocyte numbers. No sea blue histiocytes were found
      in the normal marrow or polycythaemia cases. In ITP sea blue histiocytes were
      seen in two of 20 cases and in chronic myeloid leukaemia in eight of 20 cases.
      CONCLUSIONS: Sea blue histiocytes are a common cytological feature in the bone
      marrow of patients with MDS. As other disorders frequently associated with marrow
      sea blue histiocytes are relatively rare MDS is probably the most common cause of
      this phenomenon in a northern European population.

PMID- 8254091
TI  - Skeletal mastocytosis.
AB  - AIMS: To characterise the condition of skeletal mastocytosis, an uncommon cause
      of apparently "idiopathic" osteoporosis. METHODS: Transiliac crest biopsy
      specimens submitted over a period of five years were examined for nodular
      accumulation of mast cells. The cases were reviewed histologically and clinical
      follow up was obtained from hospital notes. RESULTS: Six cases of mastocytosis
      occurring in bone biopsy specimens submitted to our department were identified.
      Four patients presented initially with vertebral collapse and the other two were
      known to have extraskeletal mast cell disease at presentation. On clinical review
      of the four patients with vertebral collapse, one was found to have urticaria
      pigmentosa. This patient died from his mastocytosis, whereas the three patients
      without evidence of extraskeletal disease remain alive and well. Histological
      examination showed that patients with the poorer clinical outcome had severe
      peritrabecular fibrosis as well as mast cell nodules; those with prolonged
      disease-free survival had nodules without peritrabecular fibrosis. CONCLUSION:
      There is a form of mastocytosis which presents clinically as "idiopathic"
      osteoporosis. Clinically it does not have the same prognostic implications as
      skeletal disease in "malignant mastocytosis", running a much more benign course.

PMID- 8254092
TI  - Iron overload in multiply transfused patients who are HIV seropositive.
AB  - AIMS: To assess histologically the amount of iron deposited in liver biopsy
      specimens from HIV positive patients; and to perform estimations of liver iron on
      tissue from patients with an increase in parenchymal stainable iron. To correlate
      the amount of blood transfused and the degree of iron overload. METHODS: Liver
      biopsy specimens (n = 120) from 109 HIV positive patients, 74 of whom had AIDS,
      were examined retrospectively and the amount of iron, as visualised with Perls's
      stain, was graded. Fibrosis was assessed using connective tissue stains.
      Estimations of liver iron were performed on tissue retrieved from paraffin wax
      blocks in cases with histological grade 3 or 4 iron overload. The amount of blood
      transfused before liver biopsy was determined from the notes for each patient.
      RESULTS: Fifteen of the 120 liver biopsy specimens had significantly increased
      amounts of iron in their hepatocytes, as assessed histologically, and this was
      confirmed in seven cases by measurement of liver iron. There was a close
      correlation between the amount of blood transfused and the degree of iron
      overload. In the initial biopsy specimens only one case showed portal tract
      expansion. Three of the five patients who had repeat biopsies, however, showed
      progressive fibrosis. CONCLUSION: Multiply transfused HIV positive patients may
      develop clinically important iron overload and are at risk of developing
      progressive fibrosis. Superimposed liver disease, especially viral hepatitis, in
      these high risk patients may exacerbate the effects of the iron overload.

PMID- 8254093
TI  - Cerebrospinal fluid concentration of fibronectin in patients with HIV-1 infection
      and central nervous system disorders.
AB  - AIMS: To evaluate the fibronectin concentrations in the cerebrospinal fluid of
      HIV-1 infected patients with central nervous system disorders. METHODS:
      Fibronectin was determined by an immunoturbidimetric assay in 41 HIV-1 infected
      patients with AIDS dementia complex, progressive multifocal leucoencephalopathy,
      and opportunistic infections. RESULTS: A significant decrease in fibronectin
      concentrations in the cerebrospinal fluid of patients with AIDS and dementia
      complex and progressive multifocal leucoencephalopathy was observed, as well as
      in those with opportunistic infections of the central nervous system (p <
      0.0001). In particular, a significant decrease in fibronectin concentration in
      cerebrospinal fluid was observed in patients with cerebral toxoplasmosis and
      cryptococcal meningitis (p < 0.0001). CONCLUSIONS: Because fibronectin can bind
      to several viruses, fungi, and protozoa, it is conceivable to suppose that the
      consumption of fibronectin in the cerebrospinal fluid of patients with
      neurological disorders may be related to the binding of fibronectin to HIV
      itself, or to viral proteins, or to organisms responsible for opportunistic
      infections.

PMID- 8254094
TI  - Development of an internal quality assessment scheme in a clinical bacteriology
      laboratory.
AB  - AIM: To develop an internal quality assessment (IQA) scheme in a clinical
      bacteriology laboratory. METHODS: Over 24 months, 1230 diagnostic specimens,
      representing 0.42% of laboratory workload, were anonymised and resubmitted for
      analysis. Six hundred and twenty one (48.7%) of these gave positive culture
      results; 44 fecal and upper respiratory specimens were "spiked" (artificially
      inoculated) to increase the proportion of positive samples. RESULTS:
      Discrepancies between IQA and clinical sample results occurred in 188 cases
      (14.8%): 76.6% of these were in culture results, 13.3% in microscopy performance,
      and 10.1% in clerical recording. The culture discrepancy rate for each positive
      sample was lowest for wound (17.5%) and urine (18.1%) specimens, and highest for
      faeces (34.9%) and upper respiratory (37.7%) samples. Discrepancies in several
      areas responded to staff training and improvement in technical methods.
      CONCLUSIONS: An IQA programme of this type assesses the reproducibility of tests
      within a diagnostic laboratory when analysing common specimen types and
      organisms. It permits blind assessment of many areas of diagnostic work that are
      not readily amenable to other quality assurance methods, and it raises the
      awareness of all staff to the importance of quality in every aspect of specimen
      and data processing.

PMID- 8254095
TI  - How many microbiology consultants are needed?
AB  - It is difficult to measure medical staff workload and medical staff requirements
      in microbiology departments. A review of 14 job descriptions for consultant
      microbiologists showed that the number of hospital beds and the number of
      specimens are more reliable workload indices than the population figure. Ratios
      between beds or specimens and medical staff numbers may help to identify
      understaffed or overstaffed microbiology departments.

PMID- 8254096
TI  - Patients with haemolytic uraemic syndrome caused by Escherichia coli O157:
      absence of antibodies to Vero cytotoxin 1 (VT1) or VT2.
AB  - Serum samples from 30 patients with haemolytic uraemic syndrome (HUS), caused by
      Escherichia coli O157, and 30 apparently healthy volunteers, were used to examine
      the immune response of patients to Vero cytotoxins (VT) 1 and VT2. Patients' sera
      could not be differentiated from control sera using ELISA; and using
      immunoblotting, none of the sera had antibodies reactive with either the A or B
      subunits of VT1 or VT2. Examination of sera for antibodies to VT1 and VT2 seems
      to be of little value in the serodiagnosis of HUS caused by Vero cytotoxin
      producing E coli O157.

PMID- 8254097
TI  - Plasma coenzyme Q (ubiquinone) concentrations in patients treated with
      simvastatin.
AB  - Plasma coenzyme Q (CoQ) was measured in 20 hyperlipidaemic patients treated with
      diet and simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase); 22 hyperlipidaemic patients treated with diet with alone; and 20
      normal controls. Patients treated with simvastatin had a significantly lower
      plasma CoQ and CoQ: cholesterol ratio than either patients receiving diet alone
      or normal controls. Use of simvastatin was inversely and independently correlated
      with both CoQ (p < 0.0001) and CoQ: cholesterol ratio (p < 0.01). There was a
      significant inverse association between CoQ and dose of simvastatin (p < 0.001).
      It is concluded that simvastatin may lower the plasma CoQ concentration and this
      may be greater than the reduction in cholesterol. The possible adverse effect of
      simvastatin on the metabolism of CoQ may be clinically important and requires
      further study.

PMID- 8254098
TI  - Septic arthritis and unpasteurised milk.
AB  - Green-top, or unpasteurised, milk is an increasing source of illness. A case of a
      previously unreported cause of septic arthritis of the hip joint, secondary to
      the ingestion of raw milk is reported.

PMID- 8254100
TI  - Rheumatoid arthritis and B cell lymphoma with pathological changes of reactive
      histiocytosis.
AB  - A 67 year old woman with rheumatoid arthritis was admitted to hospital in acute
      renal failure. Her clinical features included increasing dyspnoea and oedema, and
      a computed tomogram of the abdomen showed a large mass in the retroperitoneum.
      Twenty six days later, she died, and a post mortem examination was carried out.
      The histological changes of the mass indicated B cell lymphoma of diffuse large
      cell type, with a reactive proliferation of erythrophagocytosing histiocytes.
      Immunocytochemical studies showed that the histiocytes were positive for CD-68
      and lysozyme, but negative for S-100 protein. Such neoplastic B cell
      proliferation accompanied by activation of benign looking histiocytes with
      erythrophagocytosis is very rare.

PMID- 8254099
TI  - Abnormal alkaline phosphatase of hepatic type in cerebrospinal fluid of a patient
      with intracranial metastasis from lung cancer.
AB  - High alkaline phosphatase (ALP) activity was found in the cerebrospinal fluid of
      a patient with intracranial metastases from adenocarcinoma of the lung. On
      agarose gel electrophoresis of the major ALP isoenzyme found in the cerebrospinal
      fluid, its mobility was different from those of the usual serum ALP isoenzymes.
      This abnormal mobility might be due to the linked glycan phosphatidylinositol
      anchor in the ALP molecule, as the mobility became the same as that of the common
      liver type ALP after treatment with phosphatidylinositol specific phospholipase.
      The immunochemical antigenicity of the cerebrospinal fluid ALP was identical with
      that of the common serum liver type ALP, but its sugar moiety was similar to the
      membranous liver-type ALP rather than the serum liver type ALP. The molecular
      size of the cerebrospinal fluid ALP was 140 kilodaltons, 12 less than the common
      serum liver type ALP, suggesting that the ALP in the patient's cerebrospinal
      fluid was derived from the intracranial metastatic carcinoma.

PMID- 8254101
TI  - Improved immunoturbidimetric method for rheumatoid factor testing.
AB  - The performance of two immunoturbidimetric modifications for rheumatoid factor
      (RF) testing, which differ with respect to the means of complement inactivation
      (heat treatment and inactivation with polyvinyl sulphonate), were compared in
      serum samples from 87 patients with rheumatoid arthritis (RA) and from 403
      healthy subjects. IgM-rheumatoid factor titres were also measured with an enzyme
      linked immunosorbent assay (ELISA). Both immunoturbidimetric tests gave positive
      reactions (rheumatoid factor > or = 20 IU/ml) in 74 out of the 87 (85%) RA sera.
      In cases with high RF concentrations the results after chemical inactivation
      tended to be slightly higher compared with heat inactivation. In healthy subjects
      rheumatoid factor was detected in 19/403 (4.7%) sera using heat inactivation and
      in 22/403 (5.5%) sera with chemical inactivation of complement. Interrun
      coefficient of variation in the chemical inactivation assay was 4.4%; with the
      heat inactivation method it was 8.1%. In the ELISA, a marginally better
      correlation was noted in the results obtained using chemical inactivation.
      Inactivation of complement by means of polyvinyl sulphonate offers the advantage
      of easier test performance and better reproducibility, and the results may
      reflect more accurately true rheumatoid factor concentrations.

PMID- 8254103
TI  - ACP Broadsheet No 142: November 1993. Measurement of carbon monoxide and cyanide
      in blood.

PMID- 8254102
TI  - Molecular genetics of disorders of haem biosynthesis.

PMID- 8254104
TI  - Use of histopathology services by general practitioners: recent changes in
      referral practice.
AB  - AIMS: To determine the nature and magnitude of the histopathological workload
      generated by specimens received from general practitioners and to assess the
      trends in referral practice. METHODS: All material submitted by general
      practitioners to the Leicester district histopathology service from 1989 to
      January 1993 was identified from departmental records. All GP referrals from
      October to December 1992 were also analysed. Total numbers of referrals from all
      sources were used for comparison. Specimens were also analysed according to
      diagnostic categories. RESULTS: There has been a progressive rise, both in the
      absolute number and the proportion of specimens relative to other surgical
      specimens submitted by GPs. Most are skin biopsy specimens. There were clear
      changes over the study period in the relative proportion of different types of
      lesions received, with a substantial increase in samples of benign naevi and
      papillomas. There was some evidence of a corresponding decrease in the number of
      these lesions submitted by hospital practitioners. The number of malignant skin
      tumours from GPs was small and the proportion had not increased over the study
      period. CONCLUSIONS: Histopathological workload generated by GPs is increasing
      but it still represents a small proportion of the total. The major increase is in
      benign skin lesions.

PMID- 8254105
TI  - Immunohistochemistry of neurone specific enolase with gamma subunit specific anti
      peptide monoclonal antibodies.
AB  - AIMS: To investigate the application in immunohistochemistry of gamma-subunit
      specific anti-peptide monoclonal antibodies to human neurone specific enolase
      (NSE); and to determine their reactivity with formalin fixed, wax embedded
      sections of normal tissue and neuroendocrine tumours. METHODS:
      Immunohistochemical staining was performed on sections of formalin fixed, wax
      embedded tissue with two monoclonal antibodies (NSE-P1 and NSE-P2) raised against
      different synthetic peptides specific for the gamma subunit of human enolase
      (neurone specific enolase). RESULTS: Both antibodies gave strong immunostaining
      in normal tissues and cells known to contain NSE. There was no immunoreactivity
      in tissues containing either the alpha alpha or beta beta isozymes of enolase.
      The reactivity of the antibodies with a range of neuroendocrine tumours was also
      studied and both antibodies gave strong immunostaining of tumour cells in the
      different tumours. CONCLUSIONS: The use of synthetic peptides from defined
      regions of a molecule as immunogenes provides antibodies of high specificity.
      These monoclonal antibodies to NSE are ideally suited for immunohistochemical
      studies and they should be particularly useful in histopathology as they react
      with epitopes which are resistant to formalin fixation and wax embedding.

PMID- 8254106
TI  - Gastric cancer and Helicobacter pylori infection.
AB  - AIMS: To identify differences in the prevalence of Helicobacter pylori infection
      in different groups of patients with gastric cancer. METHODS: In total 224 cases
      of gastric cancer were studied: 120 (53.6%) intestinal; 69 (30.8%) diffuse; and
      35 (15.6%) unclassified. Site of tumour, presence and severity of gastritis,
      presence and extent of intestinal metaplasia, and age and sex were also recorded.
      Infection by H pylori was assessed using modified Giemsa staining. RESULTS: H
      pylori infection was found in 96 (43%) cases. There was no significant
      association between infection and histological type of tumour, nor was there any
      significant association between infection and site of tumour, the presence of
      intestinal metaplasia, age, or sex. The only significant association identified
      was between infection and gastritis. CONCLUSIONS: These results are in broad
      agreement with those of other similar studies, although the overall prevalence of
      infection, at 43%, was lower than has been reported in some series. The findings
      do not support a role for H pylori in any particular subgroup of patients with
      gastric cancer but do not exclude a role for the organism in the pathogenesis of
      gastric cancer as a whole.

PMID- 8254107
TI  - Chemoarchitectonic subdivisions of the visual pulvinar in monkeys and their
      connectional relations with the middle temporal and rostral dorsolateral visual
      areas, MT and DLr.
AB  - The organization of the inferior pulvinar complex (PI) in squirrel monkeys was
      studied with histochemical localization of the calcium binding proteins calbindin
      D28k and parvalbumin, and of cytochrome oxidase. With each of these markers, the
      inferior pulvinar complex can be subdivided into four distinct regions. Calbindin
      D28k immunoreactivity is densely distributed in cells and neuropil within PI,
      except for a distinct centromedially located gap. This calbindin-poor zone,
      termed the medial division of the inferior pulvinar (PIM), corresponds precisely
      to a region that contains elevated cytochrome oxidase activity and parvalbumin
      immunostaining. The PIM extends slightly above and behind the classically defined
      limit of the inferior pulvinar, the corticotectal tract. Regions of inferior
      pulvinar with intense immunostaining for calbindin-D28k were the posterior
      division of the inferior pulvinar (PIP, medial to PIM) and the central division
      (PIC, lateral to PIM). A newly recognized lateral region, PIL, adjoins the
      lateral geniculate nucleus and stains more lightly for calbindin and parvalbumin
      immunoreactivity and for cytochrome oxidase. Staining patterns for calbindin,
      parvalbumin, and cytochrome oxidase in the pulvinar of rhesus monkeys closely
      resemble those shown in squirrel monkey inferior pulvinar, suggesting that a
      common organization exists in all primates. In order to examine cortical
      connection patterns of the histochemically defined compartments in the inferior
      pulvinar, injections of up to five neuroanatomical tracers (wheat germ agglutinin
      conjugated to horseradish peroxidase and fluorescent retrograde tracers) were
      placed in the same cerebral hemisphere. Single injection sites were in the middle
      temporal area (MT), and several separate injections were placed in a strip
      corresponding to the rostral subdivision of the dorsolateral area (DLr).
      Injections that involved only DLr and not MT labeled principally the PIC, and
      more sparsely PIP and PIL. DLr connections occupied a "shell" region dorsal to
      PIM that extended from PIC into the lateral and medial divisions of the pulvinar,
      PL and PM. Injection sites that included MT or were largely restricted to MT
      produced dense label in PIM and moderate label in PIC and PIL. The retinotopic
      organization within the inferior pulvinar was inferred from patterns of
      connections. Connections with cortex related most closely to central vision were
      found posteriorly in PIM and in adjacent portions of PIC as it wraps around the
      caudal pole of PIM. Cortex related to more peripheral locations in the lower
      visual field connected with more rostral PIM and PIC. Patterns of label within
      the portions of PL and PM that were immediately adjacent to PIM roughly
      paralleled those in PIM and PIC.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254108
TI  - Neurophysin-containing pathway from the paraventricular nucleus of the
      hypothalamus to a sexually dimorphic motor nucleus in lumbar spinal cord.
AB  - A model that has been widely used in the study of steroid sensitive neurons, the
      spinal nucleus of the bulbocavernosus (SNB) is a sexually dimorphic motor nucleus
      in the lower lumbar spinal cord that innervates the striated bulbocavernosus (BC)
      muscle. The BC is responsible for penile reflexes in the male rat, which are
      important in ensuring pregnancy in females. The characterization of afferents to
      the SNB aids in the understanding of the neural circuitry involved in
      reproductive behavior. We have recently identified the paraventricular nucleus
      (PVN) as a possible source of afferents to the SNB. Because the PVN is the major
      source of oxytocin/vasopressin within the central nervous system (CNS), the
      purpose of the present study was to examine and characterize a neurophysin (NP)
      containing pathway from the PVN to the SNB. The results demonstrate that neurons
      of the lateral parvicellular subnucleus of PVN, which project to levels of spinal
      cord containing SNB motoneurons, contain NP, the coproduct of oxytocin and
      vasopressin. NP-containing fibers and putative terminals were found in the region
      of the SNB and appear to contact the soma and proximal dendrites of SNB
      motoneurons which were retrogradely identified as BC-innervating. Electrolytic
      lesions, which destroy the lateral parvicellular subnucleus of PVN, abolish NP
      containing fibers in the region of the SNB, suggesting that the PVN is the source
      of these NP fibers. The results of this study indicate a NP-containing projection
      from the hypothalamus directly to SNB motoneurons. It is suggested that this
      pathway may play a role in the integration of penile reflexes with other aspects
      of male copulatory behavior that are under hypothalamic control.

PMID- 8254110
TI  - Quantitative analyses of intracellularly characterized and labeled
      thalamocortical projection neurons in the ventrobasal complex of primates.
AB  - This study describes the architecture of neurons and individual dendritic arbors
      of thirteen intracellularly labeled thalamocortical projection neurons that
      respond to non-noxious stimuli from the primate (Macaca fascicularis or Macaca
      mulatta) ventrobasal complex (VB). The neurons compose a homogeneous
      morphological class with total dendritic lengths from 10,169 microns to 21,711
      microns (mean 17,615 microns +/- 3,705). The labeled neurons were remarkably
      similar in most measured parameters including the number of dendrites (7.5 +/-
      1.2), percentage of dichotomous branching (89.8% +/- 3.4), and contribution of
      terminal branches to total dendritic length (88.4% +/- 2.0). The individual
      dendrites ranged in total length from 443 microns to 7,657 microns with a mean of
      2,346 microns (+/- 137, n = 98). There was a positive correlation between stem
      dendrite diameter and total dendrite length, making it possible to estimate the
      total size of an individual dendrite by measuring the stem dendrite diameter.
      There was only a small increase in mean path distance with increasing dendritic
      size at the whole neuron and individual dendritic levels, so that for individual
      dendrites the mean path distance of a dendrite consisting of only two segments
      was 199 microns, while the mean path distance for a dendrite with eight segments
      was only 45 microns longer. Analysis of dendrite diameter, segment order, and
      path distance shows that dendritic diameter is not reliable for determining the
      location of synaptic contacts viewed by electron microscopy onto dendritic trees.
      The small variation of measured parameters between these neurons presents a
      powerful tool for future developmental, plasticity and comparative studies of VB
      neurons.

PMID- 8254109
TI  - Cholinergic innervation of the amygdaloid complex in the human brain and its
      alterations in old age and Alzheimer's disease.
AB  - The cholinergic innervation of the human amygdaloid complex was studied
      immunohistochemically with a choline acetyltransferase (ChAT) antibody in eight
      brains: five control and three with Alzheimer's disease (AD). All amygdaloid
      nuclei displayed ChAT-immunopositive axons and varicosities. The density of these
      axons reached levels that were higher than in any other part of the forebrain
      except for the striatum. The highest level of ChAT-immunopositive profiles was
      seen in the basolateral nucleus and the second highest in the lateral part of the
      central nucleus. The basomedial, accessory basal, and cortical nuclei, the
      amygdalohippocampal and cortico-amygdaloid transition areas, as well as the
      anterior amygdaloid area, showed a moderate density of ChAT-positive varicosities
      and fibers. The lateral nucleus displayed a relatively low density of cholinergic
      innervation, and there were only rare ChAT-positive fibers in the medial nucleus.
      Although the level of cholinergic innervation in the lateral nucleus was
      relatively lower than in many of the other amygdaloid nuclei, it was
      approximately equivalent to that of entorhinal cortex, a region that receives one
      of the heaviest cholinergic inputs in the cerebral cortex. The distribution of
      the cholinergic fibers as studied by ChAT immunohistochemistry was nearly
      identical to that observed with AChE histochemistry. Quantitative densitometry in
      control specimens showed that there was no decline of amygdaloid cholinergic
      input when middle-aged subjects were compared with senescent subjects. In AD
      there was a severe and regionally selective depletion of this innervation in the
      amygdaloid complex. The cortical, accessory basal, and lateral nuclei displayed
      the most severe loss of ChAT-positive profiles, whereas the basolateral, and
      especially the central, nuclei displayed relatively little change. There was no
      consistent relationship between the loss of cholinergic fibers and the density of
      amyloid plaques and neurofibrillary tangles in amygdaloid nuclei.

PMID- 8254111
TI  - Neocortex and hippocampus contain distinct distributions of calcium-calmodulin
      protein kinase II and GAP43 mRNA.
AB  - Calcium-calmodulin protein kinase II and GAP43 are two molecules which have been
      linked to synaptic plasticity. Localization of mRNA for these molecules
      identifies the neuronal populations which have the potential to utilize these
      mechanisms. General descriptions for calcium-calmodulin protein kinase II or
      GAP43 mRNA have been previously reported. In light of recent evidence that
      suggests that at some sites these two molecules may interact, we sought to
      determine the cortical distribution in detail, and to examine the extent of
      overlap between neuronal populations containing each mRNA. To this end we have
      used in situ hybridization techniques to study the distribution of calcium
      calmodulin protein kinase II and GAP43 mRNA in adjacent sections of adult rat
      forebrain. Overall, the distribution patterns were distinct but partially
      overlapping. For both calcium-calmodulin protein kinase II and GAP43, mRNA levels
      were highest in hippocampus, allo- and neocortex, compared to moderate to low
      levels in striatum and thalamic nuclei. Within the heavily labeled regions
      certain populations expressed both calcium-calmodulin protein kinase II and GAP43
      mRNA at high levels, while other populations were selective for calcium
      calmodulin protein kinase II. In the hippocampus, the stratum pyramidale of CA1-3
      expressed high levels of both calcium-calmodulin protein kinase II and GAP43
      mRNA. Granule cells of the fascia dentata and the stratum radiatum of CA3 both
      contained moderate to high levels of calcium-calmodulin protein kinase II mRNA,
      but near background levels of GAP43 mRNA label. Within the neocortex, deep layers
      were distinguished from superficial layers by their lack of calcium-calmodulin
      protein kinase II mRNA expression within the neuropil, and the presence of GAP43
      mRNA in neurons located in layer V and the deepest part of layer VI. Thus, layer
      V and deep layer VI neurons showed high levels of label for both GAP43 and
      calcium-calmodulin protein kinase II mRNA, while neurons of superficial layers
      contained only calcium-calmodulin protein kinase II mRNA. These markers
      differentiate neuronal populations which can also be distinguished on the basis
      of their ability to undergo specific forms of synaptic plasticity. These
      different forms of plasticity may be due in part to the laminar-specific patterns
      of GAP43 and calcium-calmodulin protein kinase II mRNA that we have described.

PMID- 8254112
TI  - Localization of cholecystokinin binding sites in the adult and developing
      Brazilian opossum brain.
AB  - Cholecystokinin (CCK) is now recognized as one of the most abundant peptides in
      the mammalian central nervous system. We have previously used
      immunohistochemistry to localize CCK in the adult and developing Brazilian
      opossum brain. However, little is known about the distribution of CCK binding
      sites in the developing mammalian brain. Therefore, to further our knowledge of
      the sites of action for CCK during development, we initiated a series of studies
      to localize CCK binding sites in the adult and developing Brazilian opossum. This
      species was chosen because pups are born in a fetus-like state. Receptor
      autoradiography was performed on coronally sectioned brains of 1 to 60 day
      postnatal (PN) animals and adults with 125I-Bolton Hunter-CCK-8 as the
      radioligand. Binding is evident in the 1PN opossum brainstem and is observed in
      the developing forebrain by 5PN. Region-specific binding increases during
      development, and binding in the 35PN brain resembles the adult pattern. Binding
      is evident prior to the detection of CCK-like immunoreactivity in many areas. The
      facial motor nucleus is identifiable and exhibits high levels of binding in
      Brazilian opossum pups of 10 to 35 days of age. However, binding is undetectable
      in the facial motor nucleus of 45 and 60PN pups. In general, the binding patterns
      for CCK in the adult opossum resemble those of other mammals and likely mediate
      similar physiological functions. However, some cholecystokininergic pathways
      appear to be unique to neonatal mammals.

PMID- 8254113
TI  - Monosynaptic innervation of trigeminal motor neurones involved in mastication by
      neurones of the parvicellular reticular formation.
AB  - In order to determine whether neurones in the parvicellular reticular formation
      are in direct synaptic contact with motor neurones innervating masticatory
      muscles, a combined retrograde and anterograde transport study was carried out in
      the rat at both light and electron microscopic levels. The animals received
      injections of the retrograde tracers wheat germ agglutinin conjugated to
      horseradish peroxidase or cholera toxin B conjugated to horseradish peroxidase
      into the masticatory muscles and of the anterograde tracer biocytin into the
      ipsilateral parvicellular reticular formation. The trigeminal motor nucleus was
      then examined for both anterograde and retrograde labelling in the light and
      electron microscopes. Retrogradely labelled motor neurones were identified in the
      trigeminal motor nucleus. They were large and their locations within the nucleus
      depended on the muscle injected. In addition, terminals anterogradely labelled
      with the biocytin that was injected in the parvicellular reticular formation were
      identified throughout the motor nucleus. At the electron microscopic level, the
      retrogradely labelled cells were found to receive input both from distinct types
      of unlabelled terminals and from terminals that were anterogradely labelled from
      the parvicellular reticular formation. The labelled terminals comprised one of
      the four classes of afferent terminals, being 1-2 microns in diameter and densely
      packed with spherical vesicles. They formed mostly asymmetrical but also
      symmetrical synapses with the labelled perikarya and dendrites. Anterogradely
      labelled terminals were also observed to form both symmetrical and asymmetrical
      synaptic contacts with unlabelled structures in the motor nucleus. It is
      concluded that neurones in the parvicellular reticular formation form direct
      synaptic contact with motor neurones of masticatory muscles. This pathway may
      represent the anatomical substrate by which the reticular formation exerts at
      least part of its influence on mastication. Since the parvicellular reticular
      formation receives input from the substantia nigra pars reticulata, it is
      possible that this pathway represents a system whereby the basal ganglia directly
      influence orofacial movement.

PMID- 8254114
TI  - Location and completeness of reinnervation by two types of neurons at a single
      target: the feline muscle spindle.
AB  - Muscle spindles from the tenuissimus muscle of the cat were examined
      microscopically to assess the precision and completeness of reinnervation of
      intrafusal muscle fibers by efferent and afferent neurons. Positions of motor and
      sensory nerve terminals were charted relative to the cross-sectional area
      enclosed by the outer capsule of the spindle. Profiles of nerve endings were
      measured for normally innervated and reinnervated spindles. The tenuissimus was
      deprived of innervation by freezing its nerve, sometimes in conjunction with
      either spinal ganglion removal or ventral rhizotomy. Sensory and motor terminals
      occupied separate locales along the length of normal muscle spindles. Nerve
      terminals of efferent and afferent neurons were located in appropriate positions
      along the length of spindles when axons of both types of neurons regrew together
      and when either category of axon regenerated alone. Precise reinnervation of
      muscle spindles occurred in spite of a diminished diameter of intrafusal fibers.
      Repopulation of the spindle with motor endings was less complete than that by
      sensory endings, based on the proportion and size of the regenerated terminals.
      We conclude that under optimal conditions for axonal regrowth, efferent and
      afferent neurons reinnervate their respective regions along intrafusal muscle
      fibers but motor lags sensory reinnervation within the spindle. The mechanism by
      which positional specificity happens during reinnervation of intrafusal fibers
      requires neither an interaction between terminals of the two types of neurons nor
      target cells of normal bulk.

PMID- 8254115
TI  - Tanycytes in the sunfish brain: NADPH-diaphorase histochemistry and regional
      distribution.
AB  - NADPH-diaphorase histochemistry has been shown to be a useful method for
      identifying cells that synthesize and release nitric oxide, which is implicated
      in the modulation of a variety of neural functions, including synaptic
      transmission, cerebral blood flow, and excitotoxicity. In the sunfish brain,
      NADPH-diaphorase histochemistry stains tanycytes specifically and almost
      exclusively, allowing for a thorough examination of the morphology and
      distribution of this type of cell. Tanycytes are nonciliated, process-bearing
      ependymal and extraependymal cells that contact the ventricular surface via
      apical processes, and the pial surface via basal processes. Ependymal tanycytes
      are located at the ventricular surface, and project basal processes into the
      parenchyma of the brain. Extraependymal tanycytes are found away from the
      ventricular matrix. Some extraependymal tanycytes are small, bipolar, and tend to
      be associated with bundles of basal processes. Isolated extraependymal tanycytes
      are larger, darkly stained, and multipolar. Their basal processes terminate in
      specialized endfeet on blood vessels, neuronal somata, or the pial surface.
      Specialized types of tanycytes are found in the optic tectum, the epineurial
      septum between axonal bundles along the midline in the medulla, and in restricted
      regions on the pial surface in the medulla. The only NADPH-diaphorase-positive
      neurons are found in the commissural nucleus of area ventralis telencephali.
      Injection of horseradish peroxidase into the ventricles shows that tanycytes
      lining the third and fourth ventricles are capable of taking up the tracer and
      transporting it into their basal processes. Tanycytes are unevenly distributed in
      the brain. There is a rough rostrocaudal gradient of cell density: tanycytes are
      sparse in the telencephalon and dense in the isthmus and medulla, although cell
      density is low in the spinal cord. Not all ventricular linings contain tanycytes:
      cell density is low in the medial ventricle of the telencephalon and in the
      infundibular recess, and high along the fourth ventricle. The function of
      tanycytes in the sunfish is not known. The association of tanycytes with both the
      ventricles and blood vessels raises the possibility that they play some role in
      sampling the biochemical constituents of both compartments and communicating the
      information to neural elements. It is proposed that tanycytes react to the
      biochemical composition in the ventricle and plasma by increasing or decreasing
      nitric oxide synthesis and release, which in turn influence neuronal activity or
      cerebral blood flow.

PMID- 8254116
TI  - Crossed receptive field components and crossed dendrites in cat sacrocaudal
      dorsal horn.
AB  - The hypothesis that sacrocaudal dorsal horn neurons with crossed receptive field
      components on the tail have dendrites which cross to the contralateral dorsal
      horn was tested in a combined electrophysiological and morphological study.
      Dorsal horn cells in the sacrocaudal spinal cord of anesthetized cats were
      penetrated with horseradish peroxidase-filled microelectrodes. After mapping
      their low threshold mechanoreceptive fields, cells were iontophoretically
      injected with horseradish peroxidase. A sample of 16 well-stained cells was
      obtained in laminae III and IV. Cells with receptive fields crossing the dorsal
      midline of the tail (n = 8) had somata in the lateral ipsilateral dorsal horn,
      and some of these cells (5/8) had dendrites which crossed to the lateral
      contralateral dorsal horn. Cells with receptive fields spanning the ventral
      midline (n = 2) were located near the center of the fused dorsal horn, and one of
      these had bilateral dendrites in this region. Cells with receptive fields on the
      lateral tail, crossing neither the dorsal nor the ventral midline (n = 6), had
      cell bodies in the middle of the ipsilateral dorsal horn; half had only
      ipsilateral dendrites, and half had crossed dendritic branches. Although the
      relationship between cell receptive field (RF) location (RF center, expressed as
      distance from tips of toes) and mediolateral location of the cell body was
      statistically significant, the correlation between crossed RF components and
      crossed dendritic branches was not significant.

PMID- 8254117
TI  - Water conservation and protein metabolism in northern elephant seal pups during
      the postweaning fast.
AB  - Urine production and N output were monitored in northern elephant seal (Mirounga
      angustirostris) pups progressing through 10 weeks of a natural postweaning fast.
      Urine output declined by 84% (to 69 +/- 12 ml.day-1) at 10 weeks (P < 0.05).
      Glomerular filtration rate at 10 weeks was 51% of the 67 +/- 3 ml serum.min-1
      observed during week 1 (P < 0.05). Urine N excretion fell by 69% to 1.2 +/- 0.17
      g.day-1, while urinary concentration increased (P < 0.05). Serum urea declined
      from an initial 11 mmol.l-1 to 5-7 mmol.l-1 by 5 weeks. The fall in urinary N
      loss (and thus amino acid oxidation) was concomitant with depressed metabolic
      rate. Therefore, protein contributed little toward meeting energy demands (i.e.,
      < 4% of average metabolic rate) throughout fasting. These data indicate that
      fasting pups improve water conservation and minimize protein catabolism during
      prolonged natural fasts without an exogenous source of water.

PMID- 8254118
TI  - Effect of water restriction on energy and water balance and osmoregulation of the
      fruit bat Rousettus aegyptiacus.
AB  - The energy budget, water balance and osmoregulation of the fruit bat, Rousettus
      aegyptiacus, were studied during normal hydration and during water restriction
      (oven-dried apple diet). The water input and output were balanced during both
      normal hydration and water restriction. The kidney of the fruit bat is well
      adapted to handle the water load from its fruit diet by excreting large volumes
      (14% of the body mass per day) of dilute urine (113 +/- 25 mosmol.kg H2O-1) as
      well as reducing urine volume (-95%) and increasing urine osmotic concentration
      (555 +/- 280 mosmol.kg H2O-1) during water restriction. The haematocrit, plasma
      haemoglobin and total protein concentrations did not increase during water
      restriction and heat exposure, suggesting the conservation of plasma volume.
      Gross energy intake was not affected by water restriction. However, digested
      energy intake and digestibility were significantly reduced. The effective
      regulation of energy and water budgets during water restriction suggests that the
      fruit bat can cope with seasonal climatic changes and with variable fruit supply
      during various seasons.

PMID- 8254119
TI  - High dietary sodium chloride and body temperature in the domestic fowl and the
      glaucous-winged gull.
AB  - Arad and Skadhauge (1986) correlated plasma sodium to calcium ratio and body
      temperature in domestic fowl (Gallus domesticus) during increased dietary sodium
      chloride intake which increased plasma sodium concentration. During acclimation
      to high dietary NaCl, body temperature should increase in proportion to the
      increase in plasma sodium concentration, and body temperature should increase
      less in gulls than in chickens because salt gland secretion of NaCl by gulls
      should prevent elevation of plasma sodium concentration. Plasma osmolality,
      plasma sodium concentration, plasma concentrations of total calcium and ionized
      calcium, and body temperature and panting threshold were measured in domestic
      roosters and Glaucous-winged gulls before and after exposure to high NaCl diets.
      Gull body temperature (40.4 +/- 0.2 degrees C) increased significantly (P < 0.05)
      during salt acclimation. Rooster body temperature (41.0 +/- 0.2 degrees C) did
      not increase significantly. Plasma sodium concentration increased in gulls (5.4
      +/- 0.5%, P < 0.01) and was correlated with body temperature (r = 0.497, P <
      0.05); the 3.8 +/- 1.0% increase in plasma sodium concentration in roosters (P <
      0.01) was not, suggesting that change in body temperature might be a response to
      the magnitude of increase in plasma sodium concentration. Plasma ionized calcium
      concentration increased by 12.9 +/- 4.6% (P < 0.01) in gulls and by 5.3 +/- 1.0%
      (P < 0.01) in roosters. Plasma sodium concentration was correlated with calcium
      ion concentration in both gulls (r = 0.635, P < 0.05) and roosters (r = 0.664, P
      < 0.05). In neither species were ratios of sodium to total calcium plasma
      concentration or sodium to ionized calcium concentration altered or related to
      body temperature.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254120
TI  - The status of student research in the dental school experience.

PMID- 8254121
TI  - A comparison of serine and threonine O-glycosylation by UDP-GalNAc:polypeptide N
      acetylgalactosaminyltransferase.
AB  - O-glycosylated proteins are ubiquitous in eukaryotes and are responsible for a
      variety of biological functions. O-glycosylation is initiated by the addition of
      N-acetylgalactosamine to serine or threonine residues, though it is not clear how
      specific residues are selected for modification. We have compared serine and
      threonine glycosylation using peptide substrates based on sequences from
      erythropoietin (EPO) and von Willebrand factor (HVF) that are glycosylated in
      vivo. UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase was derived from
      rat parotid, submandibular, and sublingual glands, liver and kidney as well as
      from human colostrum. The threonine-containing substrates were glycosylated to a
      much greater extent than those containing serine for all the enzyme sources.
      Changes in reaction pH, donor concentration, or divalent cation were unable to
      increase glycosylation of serine. When the incubation time was extended, serine
      in the EPO-based peptide was found to incorporate GalNAc at a low level, in
      contrast to the serine-containing HVF peptide, which did not glycosylate at all.
      By circular dichroism, the non-glycosylating peptide was the only one of the
      series that did not exhibit random coil structure. Our data suggest that although
      the structural and sequence requirements for O-glycosylation of serine and
      threonine residues are similar, serine sites are glycosylated less effectively
      than are threonine sites in vitro.

PMID- 8254122
TI  - Interaction of the salivary glycoprotein EP-GP with the bacterium Streptococcus
      salivarius HB.
AB  - The interaction of the human salivary glycoprotein EP-GP with a number of oral
      bacterial species, following incubation with human whole saliva, has been
      investigated. EP-GP could be detected with a specific monoclonal antibody, by
      means of ELISA or by electrophoresis in combination with Western Transfer. The
      results indicated that EP-GP is bound only by Streptococcus salivarius, and not
      by the other tested strains of bacteria, Actinomyces viscosus, A. naeslundii,
      Actinobacillus actinomycetemcomitans, Bacteroides fragilis, S. gordonii, S.
      oralis, S. sanguis, S. mitis, S. mutans, S. sobrinus, S. rattus, S. constellatus,
      and S. anginosus. Binding of EP-GP to S. salivarius is mediated by a protein
      protein interaction, which was found to be pH-dependent with a maximum binding
      between pH 5 and 6. For further characterization of the binding of EP-GP to S.
      salivarius, four mutants were tested, each of them lacking different cell wall
      antigens. EP-GP was bound to all mutants in amounts comparable with the wildtype,
      in spite of the different surface antigen compositions. We were able to identify
      a 27-kD EP-GP binding protein, by extraction of S. salivarius-cell wall antigens
      and electrophoretic techniques. In addition to EP-GP, S. salivarius also bound
      two other salivary proteins, namely, secretory IgA and low-molecular-weight mucin
      (MG-2).

PMID- 8254123
TI  - Amino acid sequence of a major human amelogenin protein employing Edman
      degradation and cDNA sequencing.
AB  - The abundant hydrophobic, proline-glutamine, and histidine-rich (over 90%)
      amelogenins constitute the major class of proteins in forming extracellular
      enamel matrix. These are thought to play a major role in the structural
      organization and mineralization of developing enamel. The present report
      describes the successful sequencing of the major human amelogenin protein, by use
      of both Edman degradation and cDNA sequencing. When Edman degradation was used,
      over 75% of the primary structure of the protein was determined. This sequence
      was supplemented with cDNA sequencing studies, which revealed the predicted
      sequence of this protein. Together, they provide the complete sequence of an
      important human enamel protein. The information complements recent studies on
      bovine and human amelogenin genes. A comparison between the present results and
      the protein sequences predicted from the corresponding human amelogenin genomic
      coding regions and that of cDNA sequences of other species is described.

PMID- 8254124
TI  - A longitudinal study of dental caries in the primary teeth of children who
      suffered from infant malnutrition.
AB  - A prospective, four-year longitudinal study of 209 Peruvian children was
      conducted to evaluate the effect of a single malnutrition episode occurring at
      infancy (i.e., < 1 year of age) on dental caries in the primary teeth. Children
      were recruited into the study at age 6-11 months after they had suffered from a
      malnutrition episode and were thus classified by anthropometry as either: (1)
      Normal; (2) Wasted (low weight for height); (3) Stunted (low height for age); or
      (4) Stunted and Wasted (S and W). Eruption of the primary teeth was significantly
      delayed in all malnourished children; however, the effect of stunting--that is,
      retarded linear growth--was more pronounced and lasted longer than that of
      wasting or acute malnutrition (i.e., 2.5 vs. 1.5 years, respectively). By age 4
      years, children from group 4 (S and W) showed a significantly higher caries
      experience in the primary teeth than did those in any of the other three groups.
      In summary, this longitudinal study has confirmed previous studies in animals and
      indirect epidemiological evidence which had suggested a cause-effect relationship
      between early malnutrition and increased dental caries.

PMID- 8254125
TI  - Maxillary anterior caries associated with increased caries risk in other primary
      teeth.
AB  - It has been suggested that children with caries of maxillary anterior primary
      teeth may have increased caries incidence in other teeth. This study aimed to
      quantify the extent of posterior dental caries in those children who initially
      presented with maxillary anterior caries compared with that of those who did not.
      Data were collected for 217 Head Start children participating in a one-year study
      to determine caries risk factors. Tooth surfaces were recorded as carious,
      restored, or extracted (missing due to caries). Caries was then categorized into
      the following pattern(s): maxillary anterior (MA), pit/fissure (PF), posterior
      proximal (PP), and posterior buccal/lingual smooth surface (BL). Compared with
      children who did not initially present with the maxillary anterior pattern, those
      with the maxillary anterior pattern had 2.5 times (p < 0.01) the mean number of
      posterior decayed, missing, and filled surfaces (dmfs) and approximately 3 times
      the prevalence (p < 0.01) of the PP and BL patterns. The positive predictive
      value of the MA pattern was 86.8% for children who developed the PF pattern, and
      the negative predictive values were greater than 91% for children who did not
      develop the PP and BL patterns. The prevalence of maxillary anterior caries among
      children in this study is associated with a significantly greater caries
      incidence in posterior teeth.

PMID- 8254126
TI  - Caries prevalence in 6- to 15-year-old French children based on the 1987 and 1991
      national surveys.
AB  - The caries prevalence in a multi-stage probability sample of 18,786 children
      representative of all French children 6-15 years of age was studied in 1991 and
      compared with the results of a similar survey made in 1987. A significant decline
      in dental caries in France became evident. This decline, observed in primary as
      well as in permanent teeth, was of variable magnitude among the different age
      groups. At the age of 6, 48.6% of the children were totally caries-free in 1991.
      At the age of 12, the DMFT and DMFS indices were 2.59 and 4.72, respectively,
      representing a corresponding decrease of 38% and 37%. In 1991, more caries
      affected teeth or surfaces were filled, whereas fewer caries-affected teeth or
      surfaces were untreated. Females and children living in rural areas had a higher
      caries prevalence in both surveys. Pit-and-fissure lesions were the predominant
      caries types. Dental fluorosis was very uncommon; 96.1% of the 18,786 children
      examined in 1991 were totally free of any such lesions. Average plaque and
      calculus indices were similar in 1987 and in 1991, but a decrease of 25% was
      observed in the average gingival indices. Although the relative contributions of
      various preventive factors leading to this caries reduction are not clear, it
      should be noted that use of fluoridated salt (250 mg/kg KF) started in January,
      1987. The sale of fluoridated dentifrices and the use of fluoride tablets and
      sugar substitutes increased during the period from 1987 to 1991.

PMID- 8254127
TI  - Dentin caries recording with Schiff's reagent, fluorescence, and back-scattered
      electron image.
AB  - After being weaned, the Wistar rats (12) were fed on a sucrose diet for five
      weeks to induce dental caries. Tetracycline was injected intraperitoneally into 7
      of them to label the mineralizing dentin front. Five rats without tetracycline
      injection were used to verify spontaneous fluorescence. The evidently carious
      area under one prominent fissure from each mandibular molar hemisected sagittally
      in the midline was photographed under ultraviolet light so that autofluorescence
      would be revealed. The jaws were then stained with Schiff's reagent and
      photographed under normal light and again under ultraviolet light. The areas of
      all the lesions were quantified planimetrically as they appeared on the
      photographs. The mineral contents of the areas were verified with the back
      scattered electron images. The caries lesions revealed with Schiff's reagent also
      exhibited a change in the color of the dentin fluorescence regardless of the
      tetracycline labeling. The areas of these lesions followed the shapes of the
      lesions stained by Schiff's reagent but they were greater. Staining with Schiff's
      reagent was repeatable after the specimen was washed with ethanol for a few
      weeks. The loss of minerals was seen in the areas stained with Schiff's reaction
      but was also related to the change in dentin fluorescence, which seems to be a
      more sensitive indicator of the caries progression than Schiff's reagent,
      especially in the early phase of the carious process.

PMID- 8254128
TI  - Effect of intermittent delivery of fluoride to solution on root hard-tissue de-
      and remineralization measured by 125I absorptiometry.
AB  - The effect of intermittent fluoride levels on root hard-tissue de- and
      remineralization was studied once daily for 21 days in a pH-cycling caries model
      with simulated fluoride clearance curves. Four root hard-tissue blocks, from each
      of 12 human teeth, were cut out parallel to the cementum surface. During a daily
      15-hour period, the blocks were subjected 12 times to pH changes similar to those
      which occur in plaque after a carbohydrate intake. The fluoride was delivered
      immediately before a daily nine-hour remineralization period. Four experiments
      were independently carried out: One block from each tooth was subjected to pH
      cycling without and with fluoride delivery, simulating a rinse with 0.025, 0.2,
      and 1.0% sodium fluoride (NaF), respectively. The mineral change in the blocks
      was monitored by 125I absorptiometry and expressed as the change in transmission
      (delta T). The surface between the data points (delta T values) and the x axis
      (time points) was used as a summary measure, i.e., the area under the curve
      (AUC). When no fluoride was delivered, the delta T increased over 21 days,
      indicating loss of mineral. The AUC was, on average, 5.85 +/- 0.68 (mean +/-
      S.E.) %.day. In the 0.025% NaF-rinse experiment, there was a marked reduction in
      mineral loss, indicated by an average AUC of 1.66 +/- 0.59%.day. In both the 0.2
      and 1.0% NaF-rinse experiments, a decrease in delta T, indicating gain of
      mineral, was observed from day 2. Negative delta T values occurred after 7 and 3
      days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254129
TI  - A single-section model for enamel de- and remineralization studies. 1. The
      effects of different Ca/P ratios in remineralization solutions.
AB  - A prerequisite for the accurate measurement of differences between pre- and post
      experimental mineral profiles in single sections by quantitative microradiography
      is a high degree of reproducibility of the analytical procedures. We have
      determined the reproducibility of both the production and analyses of
      microradiographs. Lesions were made in seven single bovine enamel sections and
      radiographed three times. Each microradiograph was then analyzed on three
      different occasions by use of an image analysis system. This resulted in only
      small standard deviations in the lesion parameters. The method was used to
      determine the sites of mineral deposition in lesions in single sections during
      remineralization in three different solutions, one of which contained 1.5 mmol/L
      Ca and 0.9 mmol/L PO4 (standard solution); the other two solutions were low in
      either Ca or PO4, but all three had the same degree of supersaturation. The
      mineral profiles and lesion parameters were determined after lesion formation and
      after remineralization for 4 days, 1, 2, and 3 weeks. The decrease in IML
      (integrated mineral loss) in the lesions remineralized in the standard solution
      was greatest during the first week. Lesion profiles revealed that, under non
      standard conditions, mineral deposition was retarded in the deeper part of the
      lesion, in contrast to the even distribution of mineral deposition from the
      standard solution. Differences in IML changes and lesion profiles between these
      bovine enamel experimental groups diminished when remineralization continued for
      2 and 3 weeks. Possibly, the reactivity of mineral surfaces in newly made lesions
      affected the diffusion of remineralizing ions from low concentration solutions to
      the lesion front.

PMID- 8254130
TI  - Radiographic secondary caries prevalence in teeth with clinically defective
      restorations.
AB  - Decisions to replace existing restorations are often based on clinical findings
      of margin discrepancies and other restoration defects. Previous studies have
      suggested that such findings do not correlate well with the actual presence of
      secondary caries, and that treatment should be deferred until caries is
      clinically or radiographically evident. The purpose of this study was to assess
      the frequency with which clinically defective restorations are associated with
      radiographic secondary caries. As part of a study to assess the efficacy of
      guidelines for the ordering of dental radiographs, 6285 restored teeth in 490
      subjects were examined clinically and radiographically by three calibrated
      investigators. Specific criteria were used to determine whether restorations were
      intact or defective. Of the total, 822 teeth (13%) were judged to have clinically
      defective restorations. Of these, 113 teeth (14%) had radiographic secondary
      caries. Of the 5463 teeth with intact restorations, 5% had radiographic secondary
      caries. We found that the likelihood of radiographic secondary caries was nearly
      three-fold higher for defective restorations than for intact restorations. The
      large percentage (86%) of defective restorations with no radiographic secondary
      caries suggests, however, that replacement of all defective restorations due to
      risk of secondary caries may constitute overtreatment. The use of defective
      restoration status and presence of radiographic secondary caries as a combined
      criterion for replacement may potentially reduce such overtreatment. The
      prevalence of secondary caries under defective restorations should be determined
      clinically so that the usefulness of combining the criteria of defective
      restoration with those of radiographic secondary caries can be evaluated.

PMID- 8254131
TI  - Raman spectra of human dental calculus.
AB  - Raman spectra of human dental calculus have been observed for the first time by
      use of micro-Raman spectroscopy. The spectral features of calculus were
      influenced easily by heating caused by laser irradiation. Therefore, the
      measurements were carried out at relatively low power (5 mW, 1-micron spot size).
      The spectra could be characterized as phosphate vibrational bands due to the v1,
      v2, v3, and v4 modes. The overall spectral features did not resemble those of
      pure minerals such as brushite, octacalcium phosphate, and hydroxyapatite. There
      were spectral differences among mixed calculus particles obtained from 18 adults,
      probably due to variations in local mineral composition and differences among
      patients. However, the averaged spectral features did not vary significantly with
      formation period from 1 to 6 months. Freshly removed and stored (5-11 months)
      calculus also gave comparable Raman spectra. Measurements on a fractured sample
      indicated that Raman spectra at saliva and dentin interfaces are nearly
      identical, and major mineral constituents may not vary significantly along the
      growth axis of calculus.

PMID- 8254133
TI  - Stability of polygyne and monogyne fire ant populations (Hymenoptera: Formicidae:
      Solenopsis invicta) in the United States.
AB  - Over the past decade, polygyne red imported fire ants (Solenopsis invicta Buren)
      have been found at more and more sites across the southeastern United States. The
      objective of my study was to determine if polygyne (multiple-queen) populations
      are expanding and at what rate this might be occurring. More than 200 sites were
      inspected for polygyny in Florida and several other southeastern states. These
      sites were reinspected 1-3 yr later. Results showed that polygyne populations
      were not expanding rapidly in the areas studied (i.e., > 4-6% per yr); however,
      more data will be needed to determine if polygyne populations are expanding
      slowly (i.e., 1-2% per yr). Overall, polygyne and monogyne sites were about 95%
      stable from year to year; in other words, they did not commonly switch back and
      forth from one form to the other. As expected, average mound densities in the
      Florida survey (62 sites) remained relatively constant from 1990 to 1992.

PMID- 8254132
TI  - Enhanced diazinon susceptibility in pyrethroid-resistant horn flies (Diptera:
      Muscidae): potential for insecticide resistance management.
AB  - Dose-mortality data from 40 horn fly, Haematobia irritans (L.), populations
      revealed that susceptibility to permethrin and diazinon was negatively correlated
      (i.e., as susceptibility to permethrin decreased, toxicity of diazinon
      increased). Permethrin-resistant horn fly populations exposed for 18 wk to cattle
      tagged with ear tags impregnated with 20% (AI) diazinon resulted in a 2- to 6
      fold reduction in this resistance. These populations also had LC50s for diazinon
      that were two to five times lower than those of populations susceptible to
      permethrin. Frequency of homozygous permethrin-resistant individuals decreased as
      much as 57% after exposure to diazinon during this period.

PMID- 8254134
TI  - Influence of habitat, season, and attractant on adult behavior of the screwworm
      (Diptera: Calliphoridae) in a tropical dry zone in Costa Rica.
AB  - Influence of attractant, season, habitat, temperature, and physiological state of
      the screwworm, Cochliomyia hominivorax (Coquerel), on daily activity and
      oviposition were examined during a 122 d study in a tropical dry forest in Costa
      Rica. Flies were marked and released. Numbers of flies visiting baits increased
      during the wet season and decreased during the dry season; 3 times more flies
      were observed at baits during the wet season than were observed during the dry
      season. An average of 33 females and 3 males was observed per day during the
      study. More flies (3.6 times) were attracted to liver than to sentinel sheep;
      many flies originally marked at liver failed to return and few of them oviposited
      on sentinel sheep. Females marked at sheep were recaptured more times and
      remained in the study area longer. More females marked at sheep sites were
      recaptured (51.4-54.1%) than those marked at liver sites (32.3-44.7). More than 6
      times as many flies were observed at forest than at pasture sites. The
      physiological state of the female influenced daily activity. High temperatures
      during midday (> 31 degrees C) depressed activity and decreased the number of
      foraging hours available for flies during the dry season. Decreasing host
      resources and number of hours available for foraging may be factors that limit
      screwworm populations in the dry season.

PMID- 8254135
TI  - Oral toxicity and repellency of borates to German cockroaches (Dictyoptera:
      Blattellidae).
AB  - The oral toxicities of boric acid and disodium octaborate tetrahydrate (DSOBTH)
      in dry-mixed, wet-mixed, and water-based solution baits were determined for
      German cockroaches, Blattella germanica L., in choice and nonchoice experiments.
      In dry-mixed, nonchoice bait tests, all cockroaches died within 1 wk. Time to
      mortality decreased as the concentration of boric acid increased. The LT50s for
      DSOBTH were not significantly different for any concentrations tested. In choice
      tests, the order of LT50s of boric acid and DSOBTH were 6.25% = 12.5% > 25% = 50%
      and 25% > 12.5% > 50% > 25%, respectively. Consumption of treated and control
      baits and the differences between the LT50s of the nonchoice and choice tests
      indicate repellency of the toxicants. Most German cockroaches died in 3-6 d in
      wet-mixed nonchoice tests, but all cockroaches survived the wet-mixed choice
      tests except at the lowest concentration of boric acid. This result indicated
      repellency. In nonchoice tests with water-based solutions, all cockroaches died
      in 5 d. In choice tests with boric acid solutions, mortality did not increase at
      concentrations > 1%. Choice/nonchoice ratios indicate no repellency of water
      based solutions. In addition, consumption of treated and blank solutions was not
      significantly different for any concentration except 4% DSOBTH.

PMID- 8254136
TI  - Fecundity and oviposition in laboratory colonies of the screwworm fly (Diptera:
      Calliphoridae).
AB  - The screwworm fly is mass-produced using an artificial larval diet and an
      artificial oviposition substrate. On the artificial diet, mean fecundity was 185
      eggs per female, whereas host-reared flies averaged 280 eggs per female. Host
      reared flies were generally larger (head capsule width [HCW] > 3.6 mm) than
      laboratory-reared flies (HCW < 3.6 mm). Larger flies are generally more fecund,
      and size is related to larval nutrition. Only 75-89% of females reared on
      artificial diet and maintained at 30 degrees C were gravid at 6 d of age compared
      with 100% of host-reared females tested at 5-6 d. When gravid females were
      offered artificial substrate for oviposition, approximately 28% failed to
      oviposit and another 11% laid only partial clutches. Among all females tested for
      oviposition, 25% of the total egg production was withheld. Fecundity influenced
      oviposition, because the more mature eggs a female had, the more likely she was
      to oviposit. Supplementing the adult diet of honey and water with raw meat
      increased fecundity by 14% under normal laboratory conditions, but by as much as
      350% in flies in which larval feeding was curtailed by removal of the larvae from
      the media 1 d before the normal completion of development. Many females became
      gravid in 4-5 d at 30 degrees C versus 8-9 d at 22 degrees C. But fecundity and
      oviposition rate were more variable (less synchronous) in colonies maintained at
      the higher temperature. This suggests that there may be greater selection for
      laboratory adaptation at the higher maintenance temperatures.

PMID- 8254137
TI  - Prevalence, symptom profile, and aetiology of depression in dementia sufferers.
AB  - Ninety-two consecutive attenders at a day hospital for the assessment of dementia
      were assessed using the CAMDEX schedule. The prevalence of depression in the 58
      dementia sufferers who fulfilled the entry criteria for the study was 24.1%. The
      prevalence of depression was similar in patients with senile dementia of
      Alzheimer's type and those with vascular dementia. Patients with minimal dementia
      were significantly more likely to suffer from depression than those with mild or
      moderate dementia but there was no significant association with insight. The
      symptom profile of patients with minimal dementia was significantly correlated to
      that of patients with mild dementia and both were similar to the symptom profiles
      previously described amongst the elderly with functional depression. Physical
      illness was not associated with depression in the current sample. The
      implications of the findings are discussed.

PMID- 8254138
TI  - Platelet paroxetine binding and light therapy in winter depression.
AB  - The effect of light therapy on serotonin uptake capacity in patients suffering
      from winter depressions (seasonal affective disorders) was examined indirectly by
      using [3H]paroxetine binding to determine the number of platelet serotonin
      transporters. In patients who responded to light therapy the number of platelet
      serotonin transporters decreased significantly following treatment. In contrast,
      patients who did not respond to light therapy were found to have a relatively low
      number of serotonin transporters prior to treatment, and the number did not
      change significantly following treatment.

PMID- 8254139
TI  - Shiftwork, helplessness and depression.
AB  - Forty-three student nurses undertaking shiftwork for the first time participated
      in a study which tracked their perceptions of altered neurovegetative function,
      perceived criticism from others, sense of purpose and control and psychosomatic
      complaints. It was found that this first ever episode of shiftwork produced
      marked changes in all of the above. These findings have implications for
      circadian rhythm hypotheses of depression as well as for the methodology of
      future studies on cognitive or psychosocial variables in depression.

PMID- 8254140
TI  - Decreased lymphocyte beta-adrenoreceptor function correlates with less
      agoraphobia and better outcome in panic disorder.
AB  - Previous studies have demonstrated reduced function of peripheral beta
      adrenoreceptors in panic disorder with agoraphobia (PDA). We recently reported
      that decreased lymphocyte beta-receptor function was associated with milder
      agoraphobia and better treatment response in PDA. We now report on lymphocyte
      beta-receptor function in 12 additional patients with PDA. Lower cyclic AMP
      responses to isoproterenol were significantly correlated with milder agoraphobia
      and better response to naturalistic treatment. Lower beta-receptor density tended
      to correlate similarly with agoraphobia and treatment response. These findings
      further support the hypothesis that decreased peripheral beta-receptor function
      in PDA reflects an adaptive process associated with greater resistance to
      agoraphobia and greater capacity for recovery with treatment.

PMID- 8254141
TI  - Effect of depression on psychomotor skills, eye movements and recognition-memory.
AB  - In this study 12 depressed outpatients were compared to 12 healthy controls with
      respect to their performance on a number of cognitive tasks, including a
      recognition-memory task, and their eye movements and pupil size were recorded
      while watching a traffic film. The recognition-memory task consisted of words
      with intermediate hedonic tone (neutral words), words with high hedonic tone
      ('good' words) and words with low hedonic tone ('bad' words). Patients performed
      slower on perceptual-motor tasks which could be characterized as effort
      demanding, while no difference between groups was found on effortless tasks. In
      addition, the range of horizontal eye movements, an indication of visual span,
      was found to be less in patients. Signal-detection analysis on the recognition
      memory data showed an impairment of 'pure' memory in depressives. Analyses on
      response bias indicated that patients had more false alarms, but only with
      respect to good words. It is concluded that patients exhibit cognitive deficits,
      including memory impairment, a narrower visual span and a risky response strategy
      on good words, which may be an indication of the trouble patients have in
      processing emotionally toned words.

PMID- 8254142
TI  - Early light treatment can prevent an emerging winter depression from developing
      into a full-blown depression.
AB  - The administration of light at the development of the first signs of a winter
      depression appears to prevent it from developing into a full-blown depression.
      Not a single patient from a group of 16 treated this way became severely
      depressed during the remaining part of the winter season, whereas 5 out of 11
      from the non-treated control group did.

PMID- 8254143
TI  - Anxious and non-anxious bipolar disorder.
AB  - Eighty-one outpatients with bipolar disorder (BD) were grouped by SADS anxiety
      symptom scores (high vs. low) or diagnosis of generalized anxiety disorder,
      and/or panic disorder. BD patients with high anxiety scores were more likely to
      have suicidal behaviour (44% vs. 19%), alcohol abuse (28% vs. 6%), cyclothymia
      (44% vs. 21%) and an anxiety disorder (56% vs. 25%) with a trend toward lithium
      non-responsiveness. Diagnosis of an anxiety disorder was related only to high
      anxiety and lower GAS scores. Thus, anxiety may have similar clinical relevance
      in BD as it does in unipolar patients.

PMID- 8254144
TI  - Desipramine does not alter plasma GABA in patients with major depression.
AB  - Low plasma GABA is a biological marker for depression in a subset of patients
      tested. Plasma GABA has been shown to reflect brain GABA activity. This marker
      has many characteristics of a trait marker for depression, including stability
      with time, and lack of influence by coincident factors such as gender, season,
      time, activity or diet. We here report that plasma GABA remained stable after 4
      weeks of treatment with desipramine in patients with major depression. Since the
      levels of plasma GABA did not change with time, nor with clinical improvement,
      plasma GABA is not a state marker of depression.

PMID- 8254145
TI  - Suicide attempts in rapid cycling bipolar disorder patients.
AB  - We studied 100 rapid cycling patients (33% of whom had truncated episodes), and
      120 non-rapid cycling bipolar patients for history of suicide attempts. In
      contrast to our hypothesis, no significant differences were found when comparing
      suicide attempt histories for these two groups.

PMID- 8254146
TI  - Effect of lofepramine on 5-HT function and sleep.
AB  - We studied the effect of the tricyclic antidepressant lofepramine (140-210 mg
      daily for 16 days) on 5-hydroxytryptamine 1A (5-HT1A) receptor sensitivity in
      healthy volunteers, using a buspirone neuroendocrine challenge paradigm (30 mg
      orally). We also studied the effect of lofepramine on platelet 5-HT content and
      sleep architecture. Lofepramine treatment did not alter the hypothermic,
      endocrine or amnesic effects of buspirone but significantly lowered platelet 5-HT
      content and decreased rapid eye movement sleep. Our findings suggest that at
      clinically used doses, lofepramine inhibits the uptake of 5-HT and produces
      changes in sleep architecture characteristic of tricyclic antidepressants.
      However, lofepramine does not appear to alter the sensitivity of 5-HT1A
      receptors.

PMID- 8254148
TI  - Public health aspects of anxiety and depressive disorders.

PMID- 8254147
TI  - Fluoxetine, amitriptyline and the electroencephalogram.
AB  - Electroencephalograms recorded before and after 4 weeks treatment of depressed
      patients with fluoxetine or amitriptyline were assessed visually and by power
      spectrum analysis blind to patient, treatment and whether the recordings were
      carried out before or after treatment. No significant between-group differences
      in alpha, beta or theta activity were found on visual assessment. Power spectrum
      analysis revealed a significant decrease in the amount of beta activity at week
      4. There was no EEG evidence of drowsiness or epileptiform activity in either of
      the treatment groups.

PMID- 8254149
TI  - Comorbidity of anxiety, phobia, compulsion and depression.
AB  - The longitudinal association of several syndromal diagnoses is very frequently a
      direct consequence of modern descriptive diagnosis. Comorbidity in this sense is
      clinically relevant. Comorbid cases are more severe, are more amenable to
      treatment and are more frequently suicidal. The level of association between
      psychiatric syndromes can lead to nosologic hypotheses that can be further
      examined by independent investigations, and especially by means of family
      studies. Generalized anxiety disorders are very closely associated with the
      affective disorders, particularly with depressions and suicide attempts, but also
      with hypomania. There is no close relationship with panic disorder. Social
      phobias are highly associated with agoraphobia, but also with simple phobia; also
      with panic, obsessive-compulsive syndromes and substance abuse. The prevalence of
      obsessive-compulsive syndromes depends to an exceptional degree on the
      definition. Syndromes below the diagnostic threshold of DSM-III are extremely
      frequent, and longitudinally a fluctuation about this threshold is apparent. OCS
      are especially found to be associated with social phobia and agoraphobia as well
      as with dysthymia and recurrent brief depression, but less with major depression.

PMID- 8254150
TI  - The genetic epidemiology of unipolar depression and panic disorder.

PMID- 8254151
TI  - Serotonin dysfunction syndromes: a functional common denominator for
      classification of depression, anxiety, and obsessive-compulsive disorder.

PMID- 8254152
TI  - Is minor depression a valid diagnostic concept?

PMID- 8254153
TI  - Subaffective personality disorders.

PMID- 8254154
TI  - Obsessive compulsive disorder is not an anxiety disorder.

PMID- 8254155
TI  - Amebiasis and "nonpathogenic" intestinal protozoa.
AB  - Infection with single or multiple species of intestinal protozoa is common in
      humans and can result in either asymptomatic colonization or symptoms of
      intestinal disease. Entamoeba histolytica serves as a paradigm for invasive
      colonic protozoal infection. The key to diagnosis and treatment of amebiasis is
      knowledge of the epidemiologic risk factors and clinical manifestations, a
      rational approach to diagnosis, and an understanding of the sites of action and
      uses of anti-amebic drugs. This knowledge of treatment provides a context for
      consideration of intestinal infection with less common protozoan pathogens such
      as Dientamoeba fragilis and Balantidium coli and 'nonpathogenic' protozoa such as
      Blastocystis hominis and Entamoeba coli.

PMID- 8254156
TI  - Chagas disease. American trypanosomiasis.
AB  - Chagas disease, caused by the protozoan parasite, Trypanosoma cruzi, is a major
      source of morbidity and death in Latin America. Many infected immigrants from
      that region now reside in the United States, posing a risk of transfusion
      associated transmission of the organism. Serologic testing is the cornerstone of
      diagnosing chronic T. cruzi infections, and improved assays are needed. Drug
      treatment is problematic because the two available drugs can have severe side
      effects and lack efficacy. T. cruzi infection can be particularly severe in
      immunosuppressed patients.

PMID- 8254157
TI  - Giardiasis. Issues in diagnosis and management.
AB  - Giardia lamblia is a frequent cause of diarrhea throughout the United States and
      the world. Advances in basic biology indicate that different strains of Giardia
      exist, that mammals can be infected with G. lamblia-type organisms, and that
      secretory IgA is important to host protection. Although water remains the most
      common mode of transmission of Giardia, there has been an increase in the number
      of person-to-person cases, especially related to children in day care, as well as
      an increase in food-borne cases. New antigen detection assays have improved the
      ability to diagnose Giardia in the stool and make it unlikely that duodenal
      sampling will be necessary. Metronidazole has become the drug of choice for most
      cases of giardiasis because of its efficacy, favorable tolerance, and
      availability. For pregnant women who require treatment, a non-absorbable
      aminoglycoside, paromomycin, may be tried first and metronidazole used if initial
      treatment fails.

PMID- 8254158
TI  - Leishmaniasis.
AB  - Leishmanial infections include three major clinical syndromes: visceral,
      cutaneous, and mucosal leishmaniasis. Visceral leishmaniasis, usually due to
      Leishmania donovani, has received increasing attention in the United States
      because of the growing number of cases seen in AIDS patients and the occurrence
      of viscerotropic L. tropica disease among Persian Gulf war participants.
      Cutaneous leishmaniasis is a relatively benign disease caused by L. Mexicana and
      L. (Viannia) species in the New World, and L. major, L. tropica, and L.
      aethiopica in the Old World. Many of these cutaneous lesions are self-healing,
      and treatment recommendations vary and continue to undergo evolution and study.
      Mucosal disease, caused by Leishmania (V.) braziliensis, is difficult to diagnose
      as well as to treat. A practical approach to the clinical presentation,
      diagnostic measures, and some treatment options of these syndromes is presented
      in relation to specific case studies.

PMID- 8254159
TI  - Malaria. Principles of prevention and treatment.
AB  - In the United States, effective malaria prevention strategies for short-term
      travelers are available. Monitoring trends in imported malaria and continued
      evaluation of the effectiveness and chemoprophylaxis will allow prevention
      recommendations to evolve as the risk of infection and effectiveness of
      antimalarial drugs change. Our challenge is to increase the number of prospective
      travelers receiving pre-travel advice, to disseminate this information to health
      care providers, and to improve the quality of the advice given. The early
      recognition of Plasmodium infection and the institution of prompt and effective
      treatment will reduce morbidity and mortality from malaria in this country.

PMID- 8254160
TI  - Parasitic infections in AIDS patients. Cryptosporidiosis, isosporiasis,
      microsporidiosis, cyclosporiasis.
AB  - AIDS is characteristically associated with several intracellular enteric
      protozoan infections that often cause chronic and sometimes fatal intractable
      large-volume diarrhea. Until the AIDS epidemic, several of these parasitic
      infections were almost unknown as causes of human disease. This article reviews
      the diseases produced by cryptosporidia, isospora, cyclospora, and microsporidia
      in humans.

PMID- 8254161
TI  - Issues in toxoplasmosis.
AB  - Toxoplasma has become a well-recognized cause of disease in the last decade,
      primarily due to the prominence of AIDS. Diagnosis of toxoplasmic encephalitis is
      discussed, with emphasis on serologic tests, their pitfalls, and empiric
      therapeutic trials. Randomized trials for treatment of toxoplasmic encephalitis
      are few, but the combinations of pyrimethamine and sulfadiazine and of
      pyrimethamine and clindamycin appear comparable. Needs and methods for specific
      prophylaxis of toxoplasmic encephalitis are not well defined. It is now feasible
      to diagnose Toxoplasma infection in utero with a high degree of sensitivity and
      specificity, but whether such diagnosis is effective in the usual practice
      situation in the United States remains to be proved. Toxoplasmosis in transplant
      recipients is reviewed briefly.

PMID- 8254162
TI  - Echinococcal disease.
AB  - Diagnosis of infection by the larval stages of Echinococcus granulosus, E.
      multilocaris, and E. vogeli, has increased in most parts of the world because of
      improved diagnostic technology, active surveillance, and increasing rates of
      transmission. Specific immunodiagnostics and sophisticated imaging techniques
      have made diagnosis more sensitive and specific. Surgery, performed by an
      experienced team with adequate postoperative support, remains the mainstay of
      therapy; however, alternative treatments, including chemotherapy and percutaneous
      cyst drainage, are used increasingly to aid in the management of inoperable
      echinococcal disease and, in some cases, for primary therapy. This article
      incorporates data from widely disparate sources and attempts a summary of the
      state-of-the-art diagnosis and treatment of echinococcal disease.

PMID- 8254163
TI  - Filarial infections.
AB  - The seven filarial parasites of humans infect over 100 million people worldwide.
      These parasites are long lived, with adults living an average of 10 to 15 years
      and the microfilaria, probably 6 to 12 months. Importantly, as with most other
      helminth parasites, there is no replication of the adult parasite within the
      human host so that the extent of infection (that is, the number of adult worms
      one has) never increases after one leaves an endemic region and ceases to be
      exposed to the insect-borne infective larvae. This article will discuss the
      diagnosis and treatment of filarial infections, as well as some recent clinical
      advances.

PMID- 8254164
TI  - Schistosomiasis.
AB  - Schistosomiasis is a curable parasitic infection that, if left untreated, can
      persist for 30 years even though the parasite cannot reproduce in its human host.
      Tissue pathology, particularly of the GI and GU tracts, is associated with the
      granulomatous immune response to parasite eggs. Schistosomiasis is not endemic to
      the United States because the specific snail intermediate hosts required for
      transmission are absent. Physicians in North America will see acute and chronic
      forms of schistosomiasis in travelers and former residents of endemic areas.
      Therapy with praziquantel is indicated for all species of schistosomes and all
      clinical manifestations of schistosomiasis.

PMID- 8254165
TI  - Strongyloidiasis and other intestinal nematode infections.
AB  - In contrast to other helminthic parasites, Strongyloides stercoralis can
      replicate within humans, causing a chronic persistent infection that can be
      severe and fatal in compromised hosts. This article reviews new developments to
      help meet the clinical challenges of this infection, including clinical clues to
      the diagnosis, new diagnostic methods, including stool culture and serological
      assays, new drugs such as albendazole and ivermectin, and difficult treatment
      issues. The other major intestinal nematode parasites, including Ascaris,
      hookworm, and Trichuris, are extremely common worldwide, but in North America
      their clinical presentation is often more subtly related to low-grade worm
      burdens or allergic manifestations. Special consideration is given to difficult
      management issues, including the patient with unexplained eosinophilia, the
      pregnant patient, and the patient who passes a worm.

PMID- 8254166
TI  - Taeniasis and cysticercosis.
AB  - This article focuses on clinical issues of taeniasis and cysticercosis, including
      a comprehensive review of the clinical data, standard and latest chemotherapy,
      modern concepts of pathogenesis, conventional and advanced diagnostic tests,
      current epidemiology, and effective means of control. Fundamental parasitology is
      covered to familiarize physicians and scientists with the latest concepts of
      parasites.

PMID- 8254167
TI  - Trematode infections. Opisthorchiasis, clonorchiasis, fascioliasis, and
      paragonimiasis.
AB  - The parasitic diseases of the liver and lung are caused by trematodes or flukes-
      Opisthorchis viverrini, O. felineus, Fasciola hepatica, and Paragonimus
      westermani. Humans get infected by eating the second intermediate host of the
      fluke, for example, fish, crab, or water plant. The disease runs a chronic
      course. The diagnosis is made by the recover of eggs in stools or sputum, or by
      serodiagnosis. Praziquantel is the drug of choice except in falcioliaisis.

PMID- 8254168
TI  - Zoonotic roundworm infections.
AB  - The larval stage of several animal parasites can infect humans and produce severe
      disease. Visceral and ocular larval migrans caused by the common dog roundworm,
      Toxocara canis, are two well-recognized clinical syndromes. With the wider
      availability of serodiagnostic tests for toxocaral infection, other syndromes
      characterized by neuropsychologic deficits, epilepsy, asthma, abdominal distress,
      and chronic allergy have been described. Treatment with corticosteroids in
      conjunction with anthelminthic drugs may be life- or sight-saving. Recognition of
      the risk factors for infection is key to prevention, reinfection, and more
      serious illness.

PMID- 8254169
TI  - Bibliography of the current world literature in hypertension.

PMID- 8254170
TI  - The kidney and primary hypertension: contributions from renal transplantation
      studies in animals and humans.
AB  - CLINICAL STUDIES: In clinical renal transplantation studies, recipients of a
      renal graft from a donor with a genetic predisposition to hypertension had higher
      blood pressures and required more antihypertensive treatment than recipients of a
      renal graft from a normotensive donor. In addition, blood pressure normalization
      in patients suffering from essential hypertension by bilateral nephrectomy and
      subsequent transplantation of a kidney from a normotensive donor has been
      reported. The interpretation of these data may be limited by the large number of
      different factors that can contribute to post-transplantation hypertension in
      human renal transplant recipients. EXPERIMENTAL STUDIES: In experimental renal
      transplantation studies the contribution of individual factors to post
      transplantation hypertension can be independently assessed. Besides immunological
      graft rejection and hypertension-induced damage to the renal graft, a genetic
      predisposition to hypertension in the kidney donor has been demonstrated to be
      associated with post-transplantation hypertension in the recipient. Thus,
      normotensive recipients of a renal graft from a genetically hypertensive donor
      consistently developed post-transplantation hypertension in four different animal
      models of genetic hypertension. Furthermore, in genetically hypertensive rats
      bilateral nephrectomy together with transplantation of a kidney from a
      normotensive donor has been shown to be associated with a decrease in blood
      pressure. CONCLUSIONS: Hypertension following renal transplantation may be due to
      a variety of factors, including immunological graft rejection, hypertension
      induced damage to the renal transplant and a genetic predisposition to
      hypertension of the kidney donor. The finding that blood pressure is transplanted
      with the renal graft in genetic hypertension suggests a genetically determined
      alteration to the kidney as a major factor in the aetiology of primary
      hypertension. The nature of this factor is just beginning to be understood. Renal
      transplantation studies in rat models of genetic hypertension, combined with the
      tools of molecular biology, may help to provide further insights into the role of
      the kidney in primary hypertension.

PMID- 8254172
TI  - Guidelines on guidelines.

PMID- 8254171
TI  - The molecular biology of the kallikrein-kinin system: III. The human kallikrein
      gene family and kallikrein substrate.

PMID- 8254173
TI  - 1993 guidelines for the management of mild hypertension: memorandum from a World
      Health Organization/International Society of Hypertension meeting. Guidelines Sub
      Committee.

PMID- 8254174
TI  - Chromosomal assignment of human and rat hypertension candidate genes: type 1
      angiotensin II receptor genes and the SA gene.
AB  - OBJECTIVE: The chromosomal location of candidate genes for a disease, especially
      if the disease is multifactorial, is an important datum. The objective of the
      present study was to determine the chromosomal location of candidate
      hypertensinogenic genes, both in humans and in the rat, a species widely used for
      animal models of human hypertension. The type 1 angiotensin II receptor (AT1)
      genes are obvious hypertension candidate genes, whereas the SA gene has recently
      been shown to cosegregate with hypertension in the rat. DESIGN: The chromosomal
      location of the relevant genes was determined using somatic cell hybrids
      segregating either human chromosomes or rat chromosomes. The presence of the
      human or rat genes was determined by the Southern blot method, using rat probes.
      RESULTS: A single AT1 gene (AT1) was detected in the human genome, and was
      assigned to chromosome 3, whereas two non-syntenic genes were detected in the rat
      genome, corresponding to the previously identified A and B subtypes. They were
      assigned to the rat chromosome 17 (At1a) and 2 (AT1b). The Sa gene was assigned
      to human chromosome 16 and rat chromosome 1, disclosing a new synteny group
      retained on rat chromosome 1 and human chromosome 16. CONCLUSIONS: These
      chromosomal assignments should be useful for linkage analyses of genes
      controlling blood pressure. The genes that we studied, and the chromosomes that
      we identified, deserve special attention in such linkage analyses.

PMID- 8254175
TI  - Cardiovascular effects of alpha-trinositol in spontaneously hypertensive and
      normotensive Wistar-Kyoto rats.
AB  - OBJECTIVE: To investigate the cardiovascular effect of alpha-trinositol (D-myo
      inositol-1,2,6-trisphosphate; PP56) in spontaneously hypertensive rats (SHR) and
      in normotensive Wistar-Kyoto (WKY) rats. alpha-Trinositol, a representative of a
      new group of pharmacological agents, is an inositol phosphate which seems to bind
      to a single population of binding sites, inhibiting, for example, agonist-induced
      vasoconstriction. In particular, alpha-trinositol seems to inhibit agonist
      induced (e.g. neuropeptide Y-induced) elevations in intracellular Ca2+ levels in
      vascular smooth muscle cells. METHODS: alpha-Trinositol was administered as a
      bolus injection (2-40 mg/kg body weight), followed by a continuous infusion (20
      400 mg/kg body weight per h) for 40 min in freely moving SHR and WKY rats.
      RESULTS: Acute intravenous bolus administration of alpha-trinositol reduced
      systolic and diastolic blood pressure, as well as heart rate, in a dose-dependent
      manner in SHR and WKY rats. After completion of the 40-min infusion the reduction
      in blood pressure was more pronounced in the SHR than in the WKY control rats.
      Heart rate did not change in the SHR, whereas it was significantly increased at
      the highest dosage (400 mg/kg) in the WKY rats. At this dosage, three out of
      eight SHR died from cardiac arrhythmias after completing the infusion. The lowest
      dose of alpha-trinositol administered (2 mg/kg bolus followed by 20 mg/kg per h
      infusion over 40 min) significantly inhibited the increase in mean arterial
      pressure induced by neuropeptide Y (2 micrograms/kg per min for 10 min) by
      approximately 30% in both the SHR and WKY rats. Furthermore, alpha-trinositol
      treatment completely inhibited the potentiation induced by neuropeptide Y (0.1
      micrograms/min for 30 min) of the blood pressure responses to intravenous bolus
      injections of noradrenaline (20 ng), tyramine (40 micrograms) or angiotensin II
      (10 ng). CONCLUSIONS: Our results demonstrate that alpha-trinositol antagonizes
      the direct postsynaptic pressor response to exogenous neuropeptide Y, as well as
      the potentiating effects of neuropeptide Y on other vasoconstrictors in SHR and
      WKY rats. However, in the SHR alpha-trinositol lowered basal blood pressure only
      in the dose range which was non-specific for neuropeptide Y inhibition. Thus, the
      present study indicates that neuropeptide Y is involved only slightly in the
      maintenance of high blood pressure in SHR.

PMID- 8254176
TI  - The vasodilatory effect of endogenous nitric oxide is a major counter-regulatory
      mechanism in the spontaneously hypertensive rat.
AB  - OBJECTIVE: A decreased responsiveness to endothelium-dependent vasodilatory
      substances is characteristically seen in isolated arteries from spontaneously
      hypertensive rats (SHR). However, the precise status and role of nitric oxide
      (NO), which is, at least in part, the endothelium-derived relaxing factor,
      remains unclear in SHR. The objective of the present study was to evaluate the
      importance of NO release in vivo. METHODS: The effect on systolic blood pressure
      of chronic administration of NG-nitro-L-arginine methyl ester (L-NAME, an NO
      synthase inhibitor) was studied. Twenty SHR and 10 Wistar-Kyoto (WKY) rats were
      given 25 mg/kg per day L-NAME by gavage. Thirteen SHR and 14 WKY rats given water
      for the same period were used as controls. Rats were killed after 15 days and the
      aortic wall cyclic GMP (cGMP, the second messenger of NO) and cGMP-dependent
      kinase (the effector of cGMP) concentrations were assessed. RESULTS: During the
      trial, 11 of the 20 SHR given L-NAME died. Mean +/- SD systolic blood pressure
      increased from 131 +/- 8 to 171 +/- 10 mmHg in WKY rats given L-NAME and from 185
      +/- 10 to 249 +/- 22 mmHg in SHR given L-NAME. Aortic cGMP content was similar in
      control WKY rats (2122 +/- 707 fmol/mg protein) and in control SHR (2098 +/- 704
      fmol/mg protein), and was decreased in the L-NAME-treated WKY rats and SHR to 308
      +/- 87 and 644 +/- 222 fmol/mg protein, respectively. The aortic concentrations
      of cGMP-dependent kinase were not different in any group. CONCLUSIONS: Basal
      release of NO does not appear to be impaired in SHR, but represents a major
      counter-regulatory mechanism in this genetic model of arterial hypertension.

PMID- 8254177
TI  - Biochemical components and myocardial performance after reversal of left
      ventricular hypertrophy in spontaneously hypertensive rats.
AB  - OBJECTIVE: This study was undertaken to determine the biochemical and left
      ventricular functional changes associated with reversal of left ventricular
      hypertrophy (LVH) in spontaneously hypertensive rats (SHR). DESIGN: Male SHR and
      normotensive Wistar-Kyoto (WKY) rats, aged 19 weeks, were treated for 3 weeks
      with vehicle, amlodipine (10 mg/kg), benazepril (10 mg/kg) or the combination of
      both agents (4 mg/kg amlodipine and 4 mg/kg benazepril). Left ventricular
      function was assessed while blood was infused rapidly, at pharmacologically
      reduced and pretreatment mean arterial pressure (MAP). RESULTS: All treatments
      reduced MAP and left ventricular mass significantly in SHR. Myocardial protein,
      RNA and myocardial collagen content were reduced proportionately in all treatment
      groups in SHR, but not in WKY rats. DNA remained unchanged in all groups.
      Increased right ventricular mass was produced by amlodipine in both SHR and WKY
      rats (SHR +11.3%; WKY +9.8%), but this was prevented by cotreatment with
      benazepril. Right ventricular protein and collagen increased significantly with
      amlodipine in SHR but not WKY rats, and there were no changes in right
      ventricular RNA and DNA contents in either strain. Amlodipine improved,
      benazepril impaired and the combination of both agents maintained left
      ventricular pumping ability when pressure was increased abruptly to pretreatment
      levels in WKY rats. In contrast, when afterload was increased abruptly in SHR to
      pretreatment levels, neither amlodipine nor benazepril affected pumping ability,
      although it was enhanced by the combination. CONCLUSIONS: These data demonstrate
      that amlodipine, benazepril and their combination reduced left ventricular mass
      in SHR. This reversal of LVH was associated with proportional reductions in
      mycotic protein, RNA and collagen, but not DNA. Therefore, it seems unlikely that
      LVH reversal with these agents was associated with increased fibrous tissue or
      impaired left ventricular performance. Finally, addition of the angiotensin
      converting enzyme inhibitor prevents the increase in right ventricular mass
      produced by the calcium antagonist.

PMID- 8254178
TI  - Endogenous angiotensin II but not atrial natriuretic peptide modulates the effect
      of nicardipine on extracellular fluid partition in the rat.
AB  - OBJECTIVE: Both atrial natriuretic peptide (ANP) and the dihydropyridine
      derivative nicardipine lower arterial pressure and induce a shift of plasma fluid
      from the vascular towards the interstitial compartment. Because some calcium
      antagonists increase the plasma concentration of ANP, and the effect of ANP on
      transcapillary fluid shift requires the presence of angiotensin II, we examined
      the consequences of blocking the ANP and renin-angiotensin systems on the
      hypotensive and haemoconcentrating effects of nicardipine. METHODS: We evaluated
      the effects of 45-min 0.1 or 1 micrograms/kg per min nicardipine infusion on
      arterial pressure and haematocrit in anaesthetized, acutely binephrectomized
      Sprague-Dawley rats. RESULTS: Infusion of nicardipine resulted in a dose
      dependent decrease in arterial pressure. Haematocrit increased by an amount
      corresponding to the decrease in plasma volume calculated for the relevant dose.
      In the presence of monoclonal anti-ANP antibodies the nicardipine-induced changes
      in haematocrit and arterial pressure were not affected. In rats pretreated for 2
      weeks with the angiotensin converting enzyme inhibitor enalapril, as well as in
      rats receiving the angiotensin II receptor antagonist losartan acutely, the
      nicardipine-induced increase in haematocrit was abolished. In enalapril-treated
      rats the increase in haematocrit was entirely restored when angiotensin II was
      infused at a subpressor dose. The nicardipine-induced decrease in arterial
      pressure was not affected by pharmacological blockade of the renin-angiotensin
      system. CONCLUSIONS: These results demonstrate that the transcapillary shift of
      fluid induced by nicardipine is independent of ANP and requires the presence of a
      functional renin-angiotensin system, whereas its hypotensive action is
      independent of both ANP and angiotensin II.

PMID- 8254179
TI  - The effect of enalapril on glomerular growth and glomerular lesions after
      subtotal nephrectomy in the rat: a stereological analysis.
AB  - INTRODUCTION: Angiotensin converting enzyme (ACE) inhibitors have a beneficial
      effect on glomerular injury in different models of renal damage. Their presumed
      nephroprotective action has been related partly to actions on glomerular growth.
      We examined the effect of prophylactic administration of a moderate dose of
      enalapril (50 mg/l in drinking water) in male Sprague-Dawley rats on a diet
      containing 40% protein and moderate NaCl. METHODS: The rats were followed for 8
      weeks after subtotal nephrectomy and compared with sham-operated matched
      controls. RESULTS: The number of glomeruli per kidney was reduced significantly
      in both the enalapril-treated and control groups. The median glomerulosclerosis
      index was significantly lower in the enalapril-treated than in the untreated
      subtotally nephrectomized rats. The mean absolute glomerular volume was
      significantly higher after subtotal nephrectomy, but was significantly lower in
      the enalapril-treated than in the untreated subtotally nephrectomized rats. The
      total numbers of cells per glomerulus and of mesangial or endothelial cells, as
      well as nuclear volumes of mesangial cells and the total capillary length per
      glomerulus, were all significantly higher after subtotal nephrectomy. These
      parameters were significantly lower in the enalapril-treated than in the
      untreated nephrectomized rats. The rise in systemic blood pressure was modest in
      the nephrectomized rats and the arteriolar volume: length ratio was unchanged by
      treatment with enalapril. CONCLUSIONS: In subtotally nephrectomized rats
      enalapril inhibits (but fails to reverse completely) the compensatory glomerular
      enlargement and the increase in mesangial cell number and activation, with a
      concomitant reduction in the development of glomerulosclerosis. The results is
      compatible with antiproliferative, and possibly antiangiogenic, actions of ACE
      inhibitors.

PMID- 8254180
TI  - Reduction of endothelin levels by the dihydropyridine calcium antagonist
      nisoldipine and a 'natural factor' in cultured human endothelial cells.
AB  - OBJECTIVE: Endothelin is thought to be related to cardiovascular disease. The
      purpose of this study was to determine whether endothelin levels could be reduced
      by a calcium antagonist and a 'natural factor'. DESIGN: Since calcium ionophores
      can induce endothelin-1 messenger RNA synthesis in cultured endothelial cells,
      the calcium antagonist nisoldipine was used in this study to determine whether it
      could reduce endothelin levels. It has been reported that coculture of
      endothelial cells and smooth muscle cells from different species and different
      parts of the body can reduce endothelin levels. This study was also designed to
      determine whether coculture of the two cell types from the same species and the
      same section of an artery could reduce endothelin levels. METHODS: Cultured
      endothelial cells from human umbilical artery (HUAEC) and umbilical vein (HUVEC)
      were treated with increasing concentrations of nisoldipine. HUAEC were cocultured
      with human umbilical artery smooth muscle cells (HUASMC). Endothelin levels were
      measured by a radioimmunoassay. RESULTS: Incubation of the HUAEC with nisoldipine
      for either 7 or 24 h resulted in a dose-dependent (10(-8)-10(-5) mol/l) reduction
      in endothelin levels in the conditioned media. Endothelin levels in cell lysates
      were not detectable in either the absence or the presence of nisoldipine. This
      suggests that the reduction of endothelin levels in the media could be due to
      inhibition of endothelin synthesis. Under the same conditions, incubation of
      HUVEC with the same concentrations of nisoldipine produced a similar
      concentration-dependent reduction in endothelin levels. Endothelin levels were
      undetectable in the conditioned media from HUASMC. Coculture of HUAEC with HUASMC
      significantly reduced endothelin levels (P < 0.01) compared with HUAEC cultured
      alone. CONCLUSIONS: Endothelin levels can be reduced by the calcium antagonist
      nisoldipine and a 'natural factor' associated with smooth muscle cells.

PMID- 8254181
TI  - Angiotensin II enhances insulin sensitivity in healthy volunteers under
      euglycemic conditions.
AB  - OBJECTIVE: It has been postulated that vasoconstrictors cause insulin resistance.
      This effect has been documented for epinephrine but not for angiotensin II (Ang
      II). The aim of this study was to investigate the effect of the latter on insulin
      sensitivity. DESIGN: In order to study the influence of subpressor doses of Ang
      II on insulin-mediated glucose uptake under euglycemic conditions, eight healthy
      volunteers were allocated in random order to sham infusion or infusion of Ang II
      (first 0.75 ng/kg per min and subsequently 1.5 ng/kg per min). In addition, in
      seven of the subjects Ang II was infused after 3 days of indomethacin
      pretreatment (150 mg/day). METHODS: Insulin-mediated glucose uptake (expressed as
      M value) was measured with the euglycemic clamp technique. Insulin levels were
      measured enzymatically, plasma renin activity, Ang II, aldosterone and C-peptide
      levels by radioimmunoassay, blood pressure by Dinamap and muscle blood flow by
      plethysmography. RESULTS: The M value after sham infusion was 7.81 +/- 1.52 mg/kg
      per min and after 1.5 ng/kg Ang II per min was 9.76 +/- 1.26 mg/kg per min (P <
      0.001). Indomethacin pretreatment did not abolish the Ang II-induced rise in the
      M value. Mean arterial blood pressure during the euglycemic clamp was unchanged
      with sham infusion and the low dose of Ang II. It increased slightly with the
      higher dose of Ang II. Inferior limb muscle perfusion was higher after infusion
      of Ang II than after sham infusion; this effect was not obliterated by
      indomethacin pretreatment. CONCLUSIONS: Ang II increases insulin-mediated glucose
      uptake: that is, it enhances insulin sensitivity by mechanisms independent of
      prostaglandins. The observations are of potential relevance to the changes in
      insulin sensitivity in some forms of hypertension.

PMID- 8254182
TI  - Abnormal immune function in malignant hypertension.
AB  - OBJECTIVE: To investigate the extent to which the immune system is influenced in
      patients with previous malignant hypertension. DESIGN: Twenty-three patients with
      malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg
      area were studied over a 3-year period. After treatment had been instituted they
      were investigated to establish the function of the cellular immune system (number
      of T lymphocytes and the proliferative response to T-cell mitogens), human
      leucocyte antigens A, B and C and frequency of autoantibodies. METHODS: The
      numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte
      stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin
      and concanavalin-A. Autoantibodies were determined with immunoassay techniques
      and leucocyte A, B and C antigens with a lymphocytotoxicity test. RESULTS: The
      frequency of T lymphocytes and their baseline thymidine incorporation were
      significantly depressed in patients with previously malignant hypertension
      compared with control subjects. The group with malignant hypertension also had a
      decreased proliferative response to concanavalin-A but not to
      phytohaemagglutinin, and they had an increased frequency of antinuclear
      antibodies. Human leucocyte antigen B15 tended to occur more frequently in
      patients with malignant and non-malignant hypertension than in control subjects,
      especially if a family history of hypertension was taken into consideration.
      CONCLUSION: The results from the present study indicate that immune mechanisms
      are involved in malignant hypertension, either secondary to the vascular damage
      or as a primary abnormality.

PMID- 8254183
TI  - Adrenoceptors on blood cells in patients with primary hypertension: correlation
      with blood pressure and related variables.
AB  - OBJECTIVE: Alterations in platelet alpha 2-adrenoceptor and mononuclear leucocyte
      beta 2-adrenoceptor characteristics in primary hypertension have been extensively
      studied. The results of the reports have not been consistent, possibly because of
      the small number of subjects in most of the studies. We therefore studied the
      blood-cell adrenoceptor characteristics in a relatively large group of primary
      hypertensive and normotensive subjects. DESIGN: Platelet alpha 2-adrenoceptor
      characteristics were compared in 65 hypertensive and 51 normotensive subjects.
      Mononuclear leucocyte beta 2-adrenoceptor characteristics were compared in 72
      hypertensives and 67 normotensives. Untreated hypertensive subjects were selected
      from the outpatient clinic and the normotensive controls were recruited by a
      newspaper announcement. METHODS: Platelets and mononuclear leucocytes were
      isolated from blood samples obtained after at least 10 min supine rest. The alpha
      2- and beta 2-adrenoceptor characteristics were determined with [3H]-rauwolscine
      and [125I]-(-1)cyanopindolol, respectively. Correlations between the adrenoceptor
      characteristics and clinical parameters of the subjects were studied. RESULTS: No
      differences in alpha 2- or beta 2-adrenoceptor densities were observed between
      the two groups. However, a significantly lower equilibrium dissociation constant
      for [3H]-rauwolscine was observed in the hypertensive group. The correlations
      between the adrenoceptor characteristics and clinical parameters were weak and
      mostly not statistically significant. The results were compared with the most
      relevant studies in the literature. CONCLUSIONS: From our study and the
      literature, we conclude that blood-cell adrenoceptor characteristics are
      unchanged in primary hypertension.

PMID- 8254184
TI  - Immunodominant mink cell focus-inducing murine leukemia virus (MuLV)-encoded CTL
      epitope, identified by its MHC class I-binding motif, explains MuLV-type
      specificity of MCF-directed cytotoxic T lymphocytes.
AB  - H-2b mice are immunologic responders to the tumorigenic MCF1233 murine leukemia
      virus (MuLV), an AKV-related virus derived from endogenous C57BL MuLV. We have
      identified an immunodominant CTL epitope that is expressed on MCF1233 MuLV
      induced lymphomas of H-2b mice. C57BL/10 (B10) mice were immunized with an
      MCF1233-induced B10 B cell lymphoma, and tumor-specific CTL cultures were
      generated in vitro. These were tested for recognition of synthetic class I
      binding MuLV peptides, selected for class I allele-specific motifs. One of 28
      candidate peptides sensitized target cells for CTL recognition. This peptide
      seems to be an immuno-dominant epitope, because it was recognized by all
      independent CTL clones, isolated from the tumor-specific bulk culture. The
      epitope (KSPWFTTL) is derived from the MCF1233 MuLV envelope (env)-p15E region
      and is shared by all endogenous AKV types of MuLV. It has an optimal length of
      eight amino acids and is presented by the Kb H-2 class I molecule. Interestingly,
      Friend, Moloney, and Rauscher (FMR) types of MuLV are not recognized by MCF MuLV
      directed CTL. The FMR env-p15E proteins have a single amino acid difference at
      the first position of the MCF1233 MuLV epitope (RSPWFTTL instead of KSPWFTTL).
      The corresponding FMR-encoded peptide bound class I H-2 Kb equally well as the
      MCF peptide, but it was poorly recognized by MCF1233 MuLV-specific CTL. Moreover,
      in the Rauscher MuLV-induced cell line RMA the FMr peptide seems not to be
      processed for recognition by CTL, which was illustrated by experiments with CTL
      elicited against this peptide. Altered TCR interaction as well as lack of
      processing thus may explain the type specificity of MCF1233 MuLV-directed CTL.

PMID- 8254185
TI  - Visualization of the endogenous NF-kappa B p50 subunit in the nucleus of
      follicular dendritic cells in germinal centers.
AB  - NF-kappa B, a 50 kDa/65 kDa (p50/p65) heterodimer, is a ubiquitous transcription
      factor involved in the positive regulation of various immune genes. The aim of
      this study was to determine whether NF-kappa B is related to a particular cell
      type and/or differentiation step during immunopoiesis. Using in situ
      hybridization on sections from non HIV hyperplastic lymph nodes, we found that
      the gene of the 105 kDa precursor of p50 was overexpressed in the light zone of
      germinal centers, with a network aspect, which suggested the involvement of
      follicular dendritic cells (FDC). By immunohistochemistry, p50 protein was
      detected in the cytoplasm and nucleus of FDC, confirming the involvement of FDC.
      Furthermore, p50 protein was detected in the cytoplasm of all lymphocytes. Thus,
      we focused our study on isolated FDC clusters from normal tonsils. As showed on
      tissue sections, we detected the p50 in both cytoplasm and nucleus of FDC. Nuclei
      of lymphocytes from FDC clusters were negative. We next studied p65 and c-Rel
      protein expression in FDC clusters. p65 was detected in the cytoplasm of FDC,
      whereas nuclei were negative. Furthermore, p65 was detected in the nuclei of some
      lymphocytes. c-Rel protein was detected only in the cytoplasm of lymphocytes and
      not in the nucleus and cytoplasm of FDC. Our results indicated that, in the
      context of T cell-dependent B cell immunopoiesis occurring in FDC clusters, p50
      is mainly related to FDC with a massive overexpression in the nuclei, whereas p65
      is expressed in a scattered manner in the nuclei of lymphocytes and c-Rel protein
      exclusively in the cytoplasm of lymphocytes from FDC clusters. These results
      suggested that the two subunits of NF-kappa B and the c-Rel protein have
      different roles in different cell types during B cell immunopoiesis.

PMID- 8254186
TI  - Structural and immunologic analysis of gene triplications in the Ig heavy chain
      constant region locus.
AB  - The Ig H chain C region is a multigene family often involved in genomic
      rearrangements leading to deleted and duplicated haplotypes, most probably
      through unequal crossing over between homologous regions within the locus. The
      frequency of these haplotypes in Italy is around 2.7% each. Using PFGE analysis
      in two unrelated Italian families we found an abnormal high m.w. band, inherited
      in a Mendelian fashion. To assess the extension of the haplotype we performed
      Southern blot analysis using several specific Ig H chain C probes. In both cases,
      the haplotype turned out to be triplicated, with three copies of the genes from
      A1 to E. In one family segregation of a duplication from EP to G4 was also
      observed. Analysis of polymorphic loci suggests that the two triplications are of
      independent origin. Serological detection of IgA2 allotypes demonstrated the
      functional activity of the genes at the 3' end of the triplicated locus, ruling
      out any major effect of these large genomic rearrangements on Ig class switching.
      Furthermore, the triplicated haplotype does not seem to give rise to any
      clinically significant immunological impairment or increase in Ig serum
      concentrations.

PMID- 8254187
TI  - A single engineered amino acid substitution changes antibody fine specificity.
AB  - During the acquisition of humoral immunity, the process of somatic hypermutation
      introduces nucleotide substitutions into expressed antibody (Ab) V region genes.
      Studies employing in vitro mutagenesis have shown that recurrent mutations
      observed in vivo often enhance the affinity of the target Ab for Ag. Here we show
      that a single amino acid replacement at position 35 in the H chain of an
      unmutated Ab with specificity for p-azophenylarsonate (Ars) confers specificity
      for the structurally related hapten p-azophenylsulfonate (Sulf) while abolishing
      specificity for Ars. The mutant Ab binds Sulf with an affinity characteristic of
      Ab produced by memory B cells. The same mutation in the somatically mutated anti
      Ars Ab 36-71, for which the Fab crystal structure is known, resulted in a
      significant shift in fine specificity from Ars to Sulf. Examination of the
      crystal structure suggests that the specificity change is caused by a decrease in
      binding site size and/or new hydrogen bond geometry. Because the mutation at
      position 35 had been observed in somatically mutated Ab elicited by immunization
      with Ars followed by Sulf, the results confirm that somatic mutation in vivo can
      alter Ab specificity. The results also support the potential of Ab engineering to
      alter antigenic specificity.

PMID- 8254188
TI  - Promoter analysis of an interferon-inducible gene associated with macrophage
      activation.
AB  - We have investigated the regulation of an activation-associated guanylate-binding
      protein gene (mGBP-1/mag-1) in murine macrophage cell lines in response to the
      cytokine IFN-gamma. One of the cell lines utilized (RAW 264.7) acquires the
      ability to kill tumor cells after IFN-gamma and LPS treatment, whereas the other
      (WEHI-3) does not. We previously have demonstrated that mGBP-1 is induced by IFN
      gamma in RAW 264.7 but not WEHI-3 cells. Here we present information concerning
      the cloning, sequencing, and initial characterization of the upstream region of
      the mGBP-1 gene as a first step towards understanding the differential control of
      this gene in RAW 264.7 versus WEHI-3 cells. Genomic fragments encompassing a
      portion of the mGBP-1 5' flanking region were inserted into vectors containing a
      luciferase reporter gene. 928 bp of upstream sequence were found to be sufficient
      for IFN-gamma-mediated induction of luciferase activity in the RAW 264.7 cell
      line. Furthermore, sequences within 100 bp of the major transcription initiation
      site conferred strong IFN-gamma responsiveness to the reporter gene. A perfect
      match to the interferon-stimulated response element (ISRE) was present within
      this region, and was shown to be essential for interferon-induced expression. An
      oligonucleotide corresponding to the mGBP-1 ISRE bestowed interferon-inducible
      expression on a heterologous minimal promoter. Site-specific mutation of the ISRE
      within the 106-bp upstream region eliminated interferon inducibility of this
      construct. Taken together, the results indicate the ISRE is necessary and
      sufficient for IFN-gamma induction of the mGBP-1 gene. Transient transfection
      assays carried out with the WEHI-3 cell line indicated that all promoter
      constructs were transcriptionally inactive in these cells, including the ISRE
      minimal promoter construct. The inability of the WEHI-3 cell line to utilize an
      ISRE after IFN-gamma induction may underlie the functional differences exhibited
      by the two cell lines after IFN-gamma stimulation.

PMID- 8254189
TI  - Scheme for ranking potential HLA-A2 binding peptides based on independent binding
      of individual peptide side-chains.
AB  - A method to predict the relative binding strengths of all possible nonapeptides
      to the MHC class I molecule HLA-A2 has been developed based on experimental
      peptide binding data. These data indicate that, for most peptides, each side
      chain of the peptide contributes a certain amount to the stability of the HLA-A2
      complex that is independent of the sequence of the peptide. To quantify these
      contributions, the binding data from a set of 154 peptides were combined together
      to generate a table containing 180 coefficients (20 amino acids x 9 positions),
      each of which represents the contribution of one particular amino acid residue at
      a specified position within the peptide to binding to HLA-A2. Eighty peptides
      formed stable HLA-A2 complexes, as assessed by measuring the rate of dissociation
      of beta 2m. The remaining 74 peptides formed complexes that had a half-life of
      beta 2m dissociation of less than 5 min at 37 degrees C, or did not bind to HLA
      A2, and were included because they could be used to constrain the values of some
      of the coefficients. The "theoretical" binding stability (calculated by
      multiplying together the corresponding coefficients) matched the experimental
      binding stability to within a factor of 5. The coefficients were then used to
      calculate the theoretical binding stability for all the previously identified
      self or antigenic nonamer peptides known to bind to HLA-A2. The binding stability
      for all other nonamer peptides that could be generated from the proteins from
      which these peptides were derived was also predicted. In every case, the
      previously described HLA-A2 binding peptides were ranked in the top 2% of all
      possible nonamers for each source protein. Therefore, most biologically relevant
      nonamer peptides should be identifiable using the table of coefficients. We
      conclude that the side-chains of most nonamer peptides to the first approximation
      bind independently of one another to the HLA-A2 molecule.

PMID- 8254190
TI  - Normal V(D)J coding junction formation in DNA ligase I deficiency syndromes.
AB  - Bloom syndrome and a clinically related syndrome represented by the cell line
      46BR have been associated with reduction in DNA ligase I activity. In these
      syndromes, DNA ligase I deficiency severely impairs the development and function
      of the immune system. We undertook analysis of DNA ligase I-deficient cells to
      determine whether the observed immune deficiency is attributable to a
      perturbation in the process of V(D)J recombination. V(D)J recombination in Bloom
      syndrome cell lines and 46BR was examined by a transient transfection assay. No
      effect on the fidelity of coding and signal junction formation in DNA ligase I
      deficient cells was observed. The frequency of V(D)J recombination in DNA ligase
      I-deficient cells was also examined using recombination substrates modified to
      function in human cells. Similar recombination frequencies were observed in
      normal and DNA ligase I-deficient cells, demonstrating that the efficiency of the
      V(D)J recombination process is unaffected by alterations in DNA ligase I
      activity. Rearranged immunoglobulin loci from Bloom syndrome cell lines and
      patient material were molecularly cloned by an inverse polymerase chain reaction
      strategy which should be applicable to a variety of human immunodeficiency
      syndromes and were indistinguishable from those found in normal bone marrow
      samples. Our data argue that the immune system defects associated with DNA ligase
      I deficiency do not result from perturbation of the V(D)J recombination pathway.

PMID- 8254191
TI  - Induction of protective immunity to Haemophilus ducreyi in the temperature
      dependent rabbit model of experimental chancroid.
AB  - The temperature-dependent rabbit model for chancroid, a sexually transmitted
      disease caused by the fastidious Gram-negative bacterium Haemophilus ducreyi, was
      used to investigate the abilities of previous infection and immunization with an
      acellular preparation of H. ducreyi to induce protective immunity. In the first
      set of experiments, animals were infected intradermally with either the 35000 or
      Cha-1 strains of H. ducreyi and then rechallenged 30 days later with both the
      homologous and heterologous strains. In animals infected with the 35000 strain,
      statistically significant protective immunity occurred only against the
      homologous strain, whereas protection against both homologous and heterologous
      challenge was obtained in rabbits previously infected with strain Cha-1. In a
      separate series of experiments, rabbits were immunized with cell envelopes from
      either strain 35000 or strain Cha-1 and then challenged with both the homologous
      and heterologous strains. In rabbits immunized with strain 35000 cell envelopes,
      significant protective immunity was observed only against challenge with the
      homologous strain. In animals immunized with strain Cha-1 cell envelopes,
      protection was obtained against both homologous and heterologous challenge.
      Histopathologic analysis of sites inoculated with strain 35000 (10(5) CFU)
      demonstrated that the inflammatory response in control animals was predominantly
      suppurative (i.e., heterophilic), whereas that of immunized animals was
      predominantly mononuclear and, at later time points, largely histiocytic. ELISA
      and Western blot analyses revealed that immunization produced a better humoral
      immune response than did infection and provided evidence for antigenic cross
      reactivity between these two strains. These results provide the experimental
      basis for continued efforts to identify potential H. ducreyi vaccinogens.

PMID- 8254192
TI  - Human epidermal Langerhans cells secrete a soluble receptor for IgG (Fc gamma
      RII/CD32) that inhibits the binding of immune complexes to Fc gamma R+ cells.
AB  - Langerhans cells (LC) express Fc gamma RII on their cell surface. In this paper,
      we demonstrate that these cells also release soluble Fc gamma RII (sFc gamma RII)
      molecules. LC express transcripts encoding a membrane-associated receptor and a
      transmembrane-deleted Fc gamma RIIA. The latter form was identified in LC culture
      supernatants using specific antibodies. CHO cells, transfected with LC-derived
      cDNA encoding the transmembrane-deleted Fc gamma RIIA, secrete sFc gamma RIIA
      that include the intracellular domain and exhibit the same backbone as the
      protein identified in LC supernatants. Secreted sFc gamma RIIA exhibits the same
      pattern of binding to human and mouse IgG subclasses as do membrane Fc gamma RII
      and inhibits the binding of immune complexes to Fc gamma RII+ cells. In addition,
      CHO cells expressing the membrane-associated Fc gamma RIIA release truncated and
      unstable Fc gamma RIIA molecules that lack the intracellular domain. Thus, sFc
      gamma RII can result from shedding of membrane molecules and/or from secretion of
      soluble receptors lacking the transmembrane domain.

PMID- 8254193
TI  - A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing
      activity.
AB  - Rabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein
      identified and purified using as an assay its capacity to bind and inhibit
      various activities of LPS. Oligonucleotide probes designed from the putative N
      terminal protein sequence were used to obtain the corresponding cDNA from a
      rabbit bone marrow cDNA library. Examination of the cDNA sequence revealed that
      the protein fragment of the putative N-terminus was actually a 37-amino-acid C
      terminal fragment. This fragment, designated CAP18(106-142), inhibits many
      activities of LPS. In the present studies, synthetic CAP18(106-142) is shown to:
      1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS
      induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages;
      3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality.
      CAP18(106-142) may have therapeutic utility for conditions associated with
      elevated concentrations of LPS.

PMID- 8254194
TI  - Production of IL-8 and monocyte chemotactic peptide-1 by peripheral blood
      monocytes. Disparate responses to phytohemagglutinin and lipopolysaccharide.
AB  - The temporal recruitment of leukocytes to a site of inflammation is dependent on
      a complex interplay of a number of soluble mediators. Recently, two families of
      chemotactic cytokines have been discovered. The -C-X-C-family, which includes IL
      8, appears to recruit neutrophils and lymphocytes. In contrast, the -C-C-family,
      which includes monocyte chemotactic peptide-1 (MCP-1), appears to recruit
      predominantly monocytes. Monocytes, after their arrival at a site of
      inflammation, could further amplify the immune response by secreting IL-8 and MCP
      1. We sought to define conditions under which human peripheral blood monocytes
      produce IL-8 and MCP-1. Using serum-free media, we found that PHA-stimulated
      monocytes expressed MCP-1 and IL-8 protein and mRNA in a dose-dependent manner.
      However, the onset of mRNA expression for MCP-1 occurred at least 3 h later than
      did the onset of IL-8 mRNA expression. IL-8 and MCP-1 gene expression by
      monocytes appeared to require de novo protein synthesis, in that cycloheximide
      blocked the expression of mRNA for both IL-8 and MCP-1 in PHA-stimulated cells.
      However, treatment of monocytes with cycloheximide resulted in the superinduction
      of IL-8 compared with control monocytes. Monocytes costimulated with PHA and LPS
      demonstrated enhanced amounts of IL-8 mRNA and protein, but sharply decreased
      amounts of MCP-1 mRNA and protein. The addition of serum to culture media
      increased both the constitutive and PHA-induced production of monocyte-derived
      MCP-1 and IL-8, but had no effect on the inhibition of PHA-stimulated MCP-1
      production by LPS. These findings suggest that distinct pathways of activation
      exist for the production of monocyte-derived IL-8 and MCP-1. The differential
      expression of these different but related polypeptides may offer a means of
      control of the type of immune cells that are recruited to a site of inflammation.

PMID- 8254195
TI  - Stimulation of mitogen-activated protein kinase activity by different secretory
      stimuli in rat basophilic leukemia cells.
AB  - Ag-induced cross-linking of IgE bound to its high affinity receptor (Fc epsilon
      RI) at the surface of basophils or mast cells triggers a number of biochemical
      events culminating in the release of several inflammatory mediators. In rat
      basophilic leukemia (RBL-2H3) cells expressing the G protein-coupled m1
      muscarinic receptor, Ag/IgE-induced cross-linking of Fc epsilon RI, calcium
      ionophore A23187, and carbachol through M1 receptors stimulated tyrosine
      phosphorylation of several proteins, including two of 42 and 44 kDa. Proteins of
      identical molecular masses were recognized by anti-MAP-kinase antibodies, and
      these immunoreactive proteins exhibited in part a slightly increased molecular
      mass on SDS polyacrylamide gels after incubation of cells with secretory stimuli.
      All stimuli led to the activation of MAP kinase, which co-purified on Mono Q
      chromatography with 42- and 44-kDa proteins, which were tyrosine phosphorylated
      in response to secretory stimuli and reacted with anti-(MAP kinase) antibodies.
      Finally, 42- and 44-kDa proteins immunoprecipitated by anti-MAP-kinase antibodies
      and anti-phosphotyrosine antibodies were recognized by anti-phosphotyrosine and
      anti-MAP-kinase antibodies, respectively. Primarily threonine and tyrosine
      residues were found to be phosphorylated in 42- and 44-kDa proteins
      immunoprecipitated from [32P]phosphate-labeled cells that had been treated with
      secretory stimuli. The dose dependence of secretagogue-induced MAP kinase
      activation correlated with that of increases in serotonin release from activated
      cells, and the maximum of MAP kinase activation coincided with the maximum rate
      of secretion. Down-regulation or inhibition of protein kinase C as well as
      incubation of cells with the tyrosine kinase inhibitor genistein markedly
      inhibited MAP kinase activation in parallel with serotonin release. Taken
      together, these findings demonstrate that 42- and 44-kDa MAP kinases are
      activated in response to secretory stimuli and provide some evidence for a
      functional link between MAP kinase activation and signaling events leading to
      mediator release in RBL cells.

PMID- 8254196
TI  - Signal transduction mechanisms for leukotriene B4 induced hyperadhesiveness of
      endothelial cells for neutrophils.
AB  - We have previously demonstrated that leukotriene B4 (LTB4) induces in vitro a
      transient state of hyperadhesiveness in cultured human umbilical vein endothelial
      cells (HUVEC) for neutrophils (PMN). The magnitude of this response is
      intermediate of that conferred by thrombin and by platelet-activating factor
      (PAF). This report shows that the LTB4 response was neither related to HUVEC
      expression of PAF (because it could not be blocked by the PAF receptor antagonist
      WEB-2086), nor to access to LTB4 receptors on neutrophils (as shown by LTB4
      receptor desensitization experiments). However, it could be partly blocked by
      treating HUVEC with an LTB4 receptor antagonist (SC-41930). LTB4 evoked a rise of
      intracellular calcium concentrations, [Ca2+]i, in the HUVEC, and the
      hyperadhesive HUVEC response to LTB4 was abrogated by buffering of [Ca2+]i by
      Quin-2. The response was not inhibited by treating HUVEC with pertussis toxin
      before LTB4. Neutrophils showed no signs of activation when adhering to LTB4
      treated HUVEC because they did not i) release lactoferrin, or ii) react with an
      increase of [Ca2+]i, and iii) they bound equally well to the stimulated
      endothelial cells after having been treated with pertussis toxin so that up
      regulation of PMN adhesion to LTB4 was abolished. LTB4-treated HUVEC did not shed
      factors that modulated neutrophil adherence or chemotaxis. Thus, LTB4 promotes
      HUVEC hyperadhesiveness for PMN, and the transduction mechanism involves calcium
      ions, may depend on a surface receptor for LTB4, but does not involve pertussis
      toxin-sensitive G proteins or PMN activation.

PMID- 8254197
TI  - Exocytosis of a subpopulation of specific granules coincides with H2O2 production
      in adherent human neutrophils.
AB  - Unlike polymorphonuclear leukocytes (PMN) that are activated in suspension, PMN
      plated onto extracellular matrix (ECM) proteins exhibited a prolonged delay in
      the onset of the respiratory burst in response to PMA, FMLP, A23187, or GM-CSF.
      The present study was focused on examining the events leading to H2O2 release in
      adherent PMN. The time course of stimulated H2O2 release from PMN plated on
      fibrinogen (FG) kinetically paralleled cell spreading and lactoferrin release. In
      contrast, the release of another specific granule component, vitamin B12-binding
      protein, preceded H2O2 generation by at least 20 min, suggesting the differential
      mobilization of subpopulations of specific granules. FMLP-stimulated PMN from a
      patient with leukocyte adhesion deficiency (LAD), lacking CD11/CD18 integrins and
      unable to adhere to FG, attached and spread on thrombospondin (TSP) and generated
      substantial amounts of H2O2. However, PMN from a second LAD patient, able to
      attach but not spread on TSP, failed to generate oxidant. These data indicated
      that PMN spreading might be a prerequisite for H2O2 generation and that CD11/CD18
      integrins are likely not the only surface receptors involved in this response.
      Exposing PMN to the intracellular Ca2+ chelators MAPTAM or BAPTA significantly
      reduced H2O2 generation in response to the receptor-mediated agonists, FMLP or GM
      CSF, but did not affect PMA-stimulated H2O2 generation. Under conditions that
      resulted in reduced H2O2 generation (i.e., MAPTAM or BAPTA plus FMLP or GM-CSF),
      lactoferrin, but not vitamin B12-binding protein, release was also reduced,
      suggesting a link between the secretion of lactoferrin-containing specific
      granules and H2O2 production. Since neither MAPTAM or BAPTA blocked PMN
      spreading, it appeared that cell spreading alone was not sufficient for H2O2
      production. Thus, the major requirement for H2O2 generation appeared to be the
      exocytosis of a distinct population of lactoferrin-containing specific granules.
      In support of this observation, PMN-like HL-60 cells, which lack specific
      granules, attached and spread on FG but failed to release H2O2. Thus, we
      postulate that the delivery of cytochrome b from lactoferrin-containing specific
      granules to the plasma membrane during activation contributes to oxidant
      production in PMN adherent to ECM proteins.

PMID- 8254198
TI  - Tyrosine phosphorylation provides an obligatory early signal for Fc gamma RII
      mediated endocytosis in the monocytic cell line THP-1.
AB  - The human monocytic cell line THP-1 expresses two classes of IgG Fc receptor (Fc
      gamma R), Fc gamma RI, a high affinity 72-kDa Fc gamma R, and Fc gamma RII, a low
      affinity 40-kDa Fc gamma R. Biochemical as well as indirect immunofluorescence
      studies demonstrated that the selective cross-linking of Fc gamma RII with either
      anti-Fc gamma RII mAb Fab followed by F(ab)2 fragments of goat anti-mouse IgG, or
      aggregated hIgG1, which represents a physiologic ligand for this receptor,
      resulted in the activation of a protein tyrosine kinase (PTK). Several distinct
      cellular proteins including the Fc gamma RII itself were specifically
      phosphorylated on tyrosine upon ligand binding. Cross-linking of Fc gamma RII
      also triggered a rapid internalization of Fc gamma RII that was dependent upon
      tyrosine kinase activity. The internalization of the receptor in endocytic
      vesicles was established by confocal microscopy. The time course of Fc gamma RII
      initiated tyrosine phosphorylation paralleled endocytic events and reached a
      maximum between 5 and 10 min after ligand binding and declined toward basal
      levels as endocytosis was completed. Identical concentrations of genistein, an
      inhibitor of PTK, blocked Fc gamma RII-mediated endocytosis as well as the
      induction of tyrosine phosphorylation of Fc gamma RII and other cellular
      proteins. Cross-linking of Fc gamma RI also induced a rapid tyrosine
      phosphorylation of cellular proteins similar to the Fc gamma RII-mediated events.
      However, Fc gamma RII was not tyrosyl phosphorylated upon Fc gamma RI activation.
      Thus Fc gamma RII is a unique substrate for the PTK activity associated with Fc
      gamma RII upon cross-linking of this receptor. These results support the
      conclusion that Fc gamma RII is capable of independent signaling on monocytic
      cells and that protein tyrosine phosphorylation is an obligatory proximal signal
      for Fc gamma RII-mediated endocytosis. Furthermore, the signaling pathways
      employed by Fc gamma RI and Fc gamma RII are likely to be distinct.

PMID- 8254199
TI  - Specificity and class distribution of Fc gamma R-specific autoantibodies in
      patients with autoimmune disease.
AB  - To investigate the prevalence of autoantibodies directed against Fc gamma RII
      (CD32) and Fc gamma RIII (CD16), 151 serum samples from patients with different
      autoimmune diseases and 25 samples obtained from healthy individuals were assayed
      by ELISA on microtiter plates coated with recombinant truncated Fc gamma RII and
      Fc gamma RIII protein. Class specificity was defined with anti-IgG, anti-IgM, and
      anti-IgA reagents. High titers of circulating IgM autoantibodies reacting with
      both Fc gamma RII and Fc gamma RIII were characteristic for SLE and rheumatoid
      arthritis patients. Sera from patients with Raynaud's syndrome showed
      predominantly IgG reactivity with Fc gamma RIII. Sera from patients with
      progressive systemic sclerosis showed both IgG and IgM Fc gamma RII and Fc gamma
      RIII reactivity. Many patients diagnosed with degenerative osteoarthritis also
      had IgG autoantibodies, directed primarily against Fc gamma RII with lesser
      reactivity toward Fc gamma RIII. Further study is needed to correlate these
      findings to clinical characteristics of the different diseases.

PMID- 8254200
TI  - Differential requirement for autoantibody-producing B cells for induction of
      lymphocytic versus granulomatous experimental autoimmune thyroiditis.
AB  - Mouse thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTG
      transfer experimental autoimmune thyroiditis (EAT) in which the thyroid cellular
      infiltrate consists primarily of mononuclear cells (lymphocytic EAT). Addition of
      anti-IL2R antibody to cultures with MTg leads to activation of cells that induce
      granulomatous EAT, accompanied by high serum anti-MTg autoantibody responses, in
      recipient mice. CD4+ T cells are required to induce both forms of EAT; whether B
      cells and/or autoantibodies produced by MTg-sensitized B cells also contribute to
      disease severity or the type of thyroid histopathology is unknown. In our study,
      B cells and autoantibody responses produced in recipient mice were reduced either
      by column removal of B cells from donor spleen cells or by treatment of recipient
      mice with anti-I-AK mAb at the time of cell transfer. These maneuvers only
      slightly reduced the severity of lymphocytic EAT but markedly reduced the
      severity and incidence of granulomatous EAT developing in recipient mice.
      Delaying the initiation of anti-I-AK treatment until 6 days after cell transfer
      was less effective in reducing anti-MTg autoantibody responses or granulomatous
      EAT. These studies all suggested that anti-MTg autoantibodies were required for
      development of granulomatous but not lymphocytic EAT. However anti-I-AK-treated
      recipients receiving injections of anti-MTg antibody or having serum antibody
      induced by prior immunization with MTg and LPS also developed less severe
      granulomatous EAT than controls. These results suggest that sensitized CD4+ T
      cells and circulating anti-MTg autoantibody are not sufficient for development of
      granulomatous thyroid lesions. It is possible that antibodies having a unique
      function or specificity are produced in mice developing granulomatous EAT or
      thyroid-infiltrating B cells may directly contribute to the granulomatous
      inflammatory response.

PMID- 8254201
TI  - Cytolysin gene expression in the islets of diabetic BioBreeding/Worcester rats.
AB  - Diabetes prone (DP) BB/Wor rats develop spontaneous autoimmune diabetes mellitus
      caused by a T cell-dependent process that destroys pancreatic beta cells. Neither
      the inciting immune system defect nor the mechanism by which beta cells are
      destroyed is known with certainty. DP rats are severely deficient in certain T
      cell subsets including CD8+ cytotoxic T cells (Tc) and RT6+ T cells. Diabetes
      resistant (DR) BB/Wor rats can be rendered diabetic if depleted of RT6+ T cells.
      To investigate the mechanisms of beta cell destruction in BB rat diabetes, we
      determined: 1) the relative abundance of Tc and NK cells in the islets of acutely
      diabetic DP and RT6-depleted DR rats and 2) expression of mRNA encoding
      cytolysin, a cytolytic pore-forming protein produced by both Tc and NK cells. We
      found that in the islets of acutely diabetic DP rats NK cells were about three
      times more abundant than in diabetic RT6-depleted DR rats. Conversely, in the
      islets of diabetic DR rats, Tc were three times more abundant than NK cells. In
      addition, cytolysin gene expression was detected in about 60% of the islets of
      both DP and DR rats. These data suggest that cytolysin may be a mechanism by
      which Tc and NK cells damage B cells in vivo.

PMID- 8254202
TI  - Induction of multiple heart autoantibodies in mice with coxsackievirus B3- and
      cardiac myosin-induced autoimmune myocarditis.
AB  - When mice of certain strains are infected with the cardiotropic virus
      coxsackievirus B3 or are immunized with mouse cardiac myosin, myocarditis,
      accompanied by immune recognition of the myocardium, ensues. That both target
      organ injury and peripheral immunization lead to similar disease manifestations
      raise questions about the role of tissue damage in eliciting autoantibodies. A/J
      mice were infected with coxsackievirus B3 or immunized with mouse cardiac myosin
      and killed at weekly intervals for 4 wk. A portion of each heart was examined
      histologically for evidence of myocarditis and antibodies were eluted from the
      remaining heart tissue. Heart eluates and serum were tested for IgG antibodies to
      myosin and to adenine nucleotide translocator and branched chain ketoacid
      dehydrogenase molecules by ELISA. At each sampling time, coxsackievirus B3
      infected mice exhibited high titers of circulating antibodies to myosin, adenine
      nucleotide translocator, and branched chain ketoacid dehydrogenase with
      successively increasing myocardial deposition of antibodies of each specificity.
      Among myosin-immunized mice, antibodies of all three specificities were eluted
      from the myocardium and were found in the serum, but only antibodies to myosin
      were present in appreciable amounts in the circulation. Antibodies to myosin,
      adenine nucleotide translocator, and branched chain ketoacid dehydrogenase were
      rarely observed in serum and heart eluates from control animals. This study
      indicates that myocardial injury may be a prerequisite for the induction of
      cardiac autoimmunity and suggests that as tissue damage accrues, recognition of
      additional cardiac Ag may occur.

PMID- 8254203
TI  - Inhibition of IgE production and normalization of airways responsiveness by
      sensitized CD8 T cells in a mouse model of allergen-induced sensitization.
AB  - The functional role of CD8 T cells in in vivo IgE production, immediate cutaneous
      reactivity, and altered airways responsiveness (AR) was examined in a murine
      model of allergen-induced sensitization. Exposure of BALB/c mice to nebulized OVA
      triggered an IgE anti-OVA response in the serum, immediate-type skin test
      responses to OVA, and the development of increased AR (as measured by nonspecific
      reactivity to electrical field stimulation). In spleens of sensitized mice,
      analysis of the distribution of CD4/CD8 T cell subpopulations revealed an
      increase in total numbers of CD8 T cells. Transfer of purified spleen CD8 T cells
      from OVA-sensitized mice (CD8OVA) to sensitized recipients reduced serum IgE anti
      OVA production by roughly 50%. Furthermore, studies of in vitro Ig production
      indicated that mononuclear cells from recipients of CD8 cells (CD8OVA > CD8PBS)
      produced less IgE and IgG1 antibodies, whereas in vitro IgG2a production was
      enhanced. The suppression of IgE production in recipients of CD8OVA T cells was
      associated with the failure to respond to intradermal challenge with OVA. The
      increase in AR found in sensitized mice was prevented after transfer of CD8OVA
      cells. When CD8 T cells from nonimmunized animals (CD8PBS) were used for the
      transfer into sensitized recipients, serum anti-OVA IgE was decreased by only
      20%, whereas skin test reactivity and AR were not significantly affected. The ex
      vivo analysis of the pattern of cytokine-producing lymphocytes by
      immunofluorescence microscopy indicated that the sensitization procedure
      increased the fraction of IFN-gamma- and IL-4-positive cells in the spleen.
      Further in vitro analysis demonstrated that a high percentage of CD8 T cells were
      positive for IFN-gamma, whereas IL-4 was produced mainly by CD4 T cells. These
      data suggest that CD8 T cells may play an important role in the negative
      regulation of IgE production and AR and that IFN-gamma may be a relevant mediator
      of the functions of CD8 T cells in this model.

PMID- 8254204
TI  - Both phosphatidylinositol 3-kinase and phosphatidylinositol 4-kinase products are
      increased by antigen receptor signaling in B cells.
AB  - The effects of Ag binding on B cell development and activation are mediated by
      intracellular signals initiated by the B cell AgR. In this report, we show that
      the B cell AgR regulates the production of inositol phospholipids involved in two
      different signal transduction pathways, the phosphatidylinositol 3-kinase (PtdIns
      3-kinase) pathway and the phospholipase C (PLC) pathway. Phosphatidylinositol 3
      phosphate (PtdIns3P), phosphatidylinositol 3,4-bisphosphate [PtdIns(3,4)P2], and
      phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] are produced by PtdIns
      3-kinase, an enzyme that appears to be an essential component of tyrosine kinase
      mediated signaling. Both PtdIns(3,4)P2 and PtdIns(3,4,5)P3 are likely to function
      as second messengers in vivo because they can activate the zeta isoform of
      protein kinase C (PKC) in vitro. We show that cross-linking of the B cell AgR
      with anti-Ig antibodies caused a five- to sixfold increase in the levels of
      PtdIns(3,4)P2 in both the mature B cell line BAL 17 and the immature B cell line
      WEHI-231. PtdIns(3,4)P2 levels increased within 15 s of anti-Ig addition and
      remained elevated for at least 5 min. AgR cross-linking also caused a slower
      increase in PtdIns3P levels (approximately 50% over control) and a small,
      transient increase in PtdIns(3,4,5)P3 levels. Thus, the B cell AgR activates the
      PtdIns 3-kinase pathway. The other inositol phospholipid signaling pathway
      involves PLC, which cleaves phosphatidylinositol 4,5-bisphosphate
      [PtdIns(4,5)P2], yielding second messengers that increase intracellular calcium
      and activate other isoforms of PKC. We analyzed the effects of AgR signaling on
      PtdIns(4,5)P2 and its precursor, phosphatidylinositol 4-phosphate (PtdIns4P).
      Consistent with its ability to activate PLC, AgR ligation decreased the levels of
      PtdIns(4,5)P2. In contrast, AgR cross-linking increased the levels of PtdIns4P.
      Increased synthesis of PtdIns4P followed by phosphorylation at the D-5 position
      may prevent depletion of PtdIns(4,5)P2. Thus, signaling by the B cell AgR
      increases the levels of PtdIns 4-kinase products and PtdIns 3-kinase products.
      The simplest interpretation of our results is that the B cell AgR activates both
      PtdIns 3-kinase and PtdIns 4-kinase.

PMID- 8254205
TI  - Effects of syngeneic anti-IgE antibodies on the development of IgE memory and on
      the secondary IgE response.
AB  - The prolonged inhibition of IgE synthesis in mice caused by perinatal inoculation
      of IgE is attributable, at least in part, to the formation of anti-IgE
      antibodies. The induction of unresponsiveness with respect to IgE synthesis
      requires that IgE be administered during a brief interval (2 to approximately 10)
      days after birth, that corresponds with the time period during which anti-IgE
      antibodies are induced. Passive administration of syngeneic anti-IgE also
      inhibits IgE synthesis. We have now investigated the effect of anti-IgE on the
      induction of memory for IgE production and on secondary IgE responses. Syngeneic
      anti-IgE antibodies were found to inhibit secondary IgE responses directly during
      immunization or after adoptive transfer of primed cells. Anti-IgE did not,
      however, prevent the induction of memory cells for IgE synthesis or cause the
      loss of memory for IgE synthesis. Inhibition of a secondary IgE response was
      found to require the presence of anti-IgE and was lost when anti-IgE antibodies
      were cleared from the mouse. After the transfer of primed cells and secondary
      challenge anti-IgE was inhibitory only when given during the first 3 to 5 days,
      after which the primed cells became resistant to inhibition. The failure of anti
      IgE to prevent the induction of IgE memory cells is discussed in terms of class
      switches that occur during the transition from IgM to IgE production.

PMID- 8254206
TI  - Recovery of T cell populations after acute graft-vs-host reaction.
AB  - We previously have observed that T dependent immune functions were deficient for
      several months after induction of acute suppressive graft-vs-host-reaction (GVHR)
      by injection of parental C57BL/10 donor spleen cells into unirradiated (B10 x
      B10.BR) F, hosts. We therefore investigated whether new T cells matured after
      acute GVHR, and whether these were tolerant of host Ag. By 8 to 17 mo after GVHR,
      the frequencies of splenic CD4 and CD8 T cells were found to be comparable to age
      matched untreated hosts, although the lymphoid organ size and hence the total
      number of T cells was significantly reduced. When GVHR was induced with a
      combination of C57BL/6 (Thy-1.2) mature lymphocytes and B6.PL (Thy-1.1) bone
      marrow stem cells, the mature donor Thy-1.2 T cells initially predominated during
      the acute GVHR. After several months, however, 75% of the CD4 and 50% of the CD8
      T cell population was derived from donor Thy-1.1% pre-T cells that had matured in
      the host. Long term GVHR spleen cells were unresponsive to host Ag in CTL assays,
      but did not suppress anti-host CTL responses. Finally, host-reactive V beta 11
      TCR expressing cells were found to be clonally deleted from splenic CD4 and CD8
      populations, consistent with intrathymic negative selection. This evidence
      suggests that the post-GVHR thymus has the capacity to produce and negatively
      select phenotypically mature CD4 and CD8 T cells and that a failure to clonally
      delete self-reactive populations is not a contributing factor to the development
      of chronic GVHR in this system.

PMID- 8254207
TI  - Identification of two V beta 7-specific viral superantigens.
AB  - The commonly used strains of laboratory mice have mouse mammary tumor viruses
      (MTV) integrated at various locations in their DNA. The number and position of
      these integrants varies from one strain of mouse to another. It has recently been
      shown that the genomes of many of the MTV code for superantigens. The predicted
      amino acid sequences of these superantigens and their specificity for TCR V beta
      differs for each MTV integrant. This study contains the predicted amino acid
      sequence and V beta specificity of two MTV superantigens that had not previously
      been analyzed. The results show that both of these MTV superantigens are specific
      for TCR that bear V beta 7, but unlike the MTV7 superantigen not for receptors
      bearing V beta 6 or V beta 8.1. The data also support the conclusion of previous
      studies that the COOH-terminal sequence of these proteins is a major factor in
      controlling their V beta reactivity.

PMID- 8254208
TI  - Epithelial transcytosis of monomeric IgA and IgG cross-linked through antigen to
      polymeric IgA. A role for monomeric antibodies in the mucosal immune system.
AB  - We recently demonstrated that the polymeric IgR (pIgR) mediates epithelial
      transcytosis of immune complexes (IC) containing dimeric IgA (dIgA). In vivo,
      this "excretory" pathway could allow direct elimination of IgA IC at the mucosal
      sites where they are likely to form. In contrast, IC containing only monomeric
      IgA (mIgA) were not transported, consistent with the specificity of pIgR for
      polymeric IgA. However, the potential exists in vivo that monomeric Ig like mIgA
      or IgG could become associated through binding to multivalent Ag with IC
      containing dIgA, and that such mixed IC could act as ligands for pIgR. In the
      present work, using Madin-Darby canine kidney epithelial cells that express pIgR,
      we showed that 125I-labeled anti-DNP mIgA or IgG in the same IC with unlabeled
      dIgA antibody and DNP-BSA Ag was vectorially transported from the basolateral to
      the apical surface and then released. However, 125I-mIgA IC or 125I-IgG IC
      (without dIgA) and 125I-mIgA or 125I-IgG in the presence of dIgA antibody (but
      without Ag) were not transported, demonstrating the necessity for monomeric Ig to
      be in an IC with dIgA to be transported. Transcytosis of mixed mIgA/dIgA or
      IgG/dIgA IC was mediated by pIgR because no transport was observed in
      untransfected, wild-type Madin-Darby canine kidney cells lacking pIgR. The data
      demonstrate that mIgA and IgG can participate along with dIgA in the "excretory"
      pathway for local elimination of IgA IC, thus providing a means by which
      monomeric antibodies have the potential to participate in the mucosal immune
      system.

PMID- 8254209
TI  - Regulation of cytokine gene expression in T helper cell subsets.
AB  - We have examined the transcriptional regulation of the Th1-specific IL-2 gene and
      the Th2-specific IL-4 gene by transient transfection of promoter-chloramphenicol
      acetyl transferase (CAT) constructs into T cell clones and by electrophoretic
      mobility shift assays. Transfection of the Th2 clone D10.G4 with IL-4 promoter
      CAT constructs demonstrated anti-CD3 inducible IL-4 promoter activity. In
      contrast, CAT constructs containing murine IL-2 promoter sequences were not
      inducible in D10.G4 cells. Transfection analyses in the Th1 clone D1.1
      demonstrated inducible IL-2 promoter activity but no IL-4 promoter activity.
      Electrophoretic mobility shift assays using well-defined regulatory elements in
      the murine IL-2 gene promoter showed that anti-CD3 stimulation of Th2 clones
      failed to induce a characteristic increase in the ratio of p65-p50:p50-p50 NF
      kappa B binding complexes in the nucleus that did occur in IL-2-producing clones.
      In addition, other protein complexes with NF-kappa B binding sequences were seen
      using lysates from Th1 and Th0 cells but not Th2 cells. Thus, expression of the
      promoter-CAT constructs directly correlates with endogenous IL-2 and IL-4 gene
      expression in Th1 and Th2 clones, confirming that the differential expression of
      IL-2 and IL-4 genes in these T cells is transcriptionally controlled.
      Furthermore, the lack of IL-2 transcription in activated Th2 cells is associated
      with the failure to generate required IL-2 gene promoter binding proteins,
      particularly NF-kappa B in the nucleus.

PMID- 8254210
TI  - Immunobiologic and biochemical properties of mutants of toxic shock syndrome
      toxin-1.
AB  - Toxic shock syndrome (TSS) is a multisystem illness caused mainly by
      Staphylococcus aureus producing TSS toxin-1 (TSST-1). A variant of TSST-1 has
      been isolated from ovine mastitis S. aureus. This toxin, TSST-ovine (TSST-O) is
      only weakly T cell mitogenic, is nonpyrogenic, does not enhance endotoxin shock,
      and does not cause TSS in the miniosmotic pump model. The sequence of the ovine
      gene (tstO) differs from the TSST-1 gene (tstH) by 14 nucleotides that change
      seven amino acids in the mature protein of which two are in the C-terminal half.
      A gene fusion containing half of both tstH and tstO was made and cloned into S.
      aureus. The fusion protein contained the two C-terminal amino acid differences
      that are in TSST-O at residues 132 and 140. The fusion protein was not T cell
      mitogenic and did not elicit TSS in two rabbit models. Additional experiments
      used mutagenesis to change the lysine residue at position 132 of TSST-O to
      glutamate (TSST-OK132E), as exists in TSST-1, and to change the lysine residue of
      the human-ovine fusion at position 132 to glutamate (TSST-11140T). Both mutants
      were pyrogenic, enhanced endotoxin shock, and caused TSS in the miniosmotic pump
      model. However, the proteins were only partially T cell mitogenic. The
      restoration of lethality of TSST-O and the human-ovine fusion by changing the
      lysine to glutamate, as exists in TSST-1, indicates that residue 132 is important
      in lethality. The failure to regenerate complete T cell mitogenicity of the same
      mutants indicates that residues 132 and 140 are important for that activity.

PMID- 8254211
TI  - IL-2-induced expression of TTK, a serine, threonine, tyrosine kinase, correlates
      with cell cycle progression.
AB  - We have recently isolated the cDNA for a unique human 97-kDa kinase, TTK, by
      expression screening of a cDNA expression library using anti-phosphotyrosine
      antibodies. When expressed in Escherichia coli, TTK can phosphorylate serine,
      threonine, and tyrosine residues. Thus TTK appears to belong to a newly described
      family of kinases able to phosphorylate all three hydroxy amino acids. This
      family of multispecific kinases includes several other kinases involved in cell
      cycle progression. In support of a possible role in regulating cell cycle
      progression, TTK message is readily detected in rapidly proliferating tissues in
      vivo including testes, thymus, bone marrow, and many malignant tumors, but not in
      benign tissues with a low proliferative rate in vivo. To determine the effect of
      cell activation and cell cycle progression on TTK expression, we measured TTK
      mRNA and protein levels as well as kinase activity in freshly isolated T cells or
      IL-2-expanded T cell blasts activated to proliferate by the addition of a variety
      of mitogens. TTK mRNA levels, protein levels, and kinase activity were greatly
      enhanced when either freshly isolated PBL or T cell blasts were activated by
      cross-linking the TCR complex by mitogenic lectins or by bypassing the TCR with
      phorbol esters and cation ionophores. Incubation with IL-2 increased TTK
      expression in PBL blasts, which proliferate in response to IL-2, but not in fresh
      PBL, which do not proliferate in response to IL-2. TTK expression was blocked by
      either cyclosporin A or FK520, which inhibit IL-2 production and could be
      recovered by the addition of exogenous IL-2. Furthermore, TTK expression was
      prevented by incubation of the cells with rapamycin, which blocks IL-2 signaling.
      Thus, TTK expression in T cells appears to be a consequence of IL2-induced cell
      proliferation. Agonist-induced TTK expression was a delayed event occurring 12 to
      24 h after activation of PBL blasts and 48 to 72 h after activation of fresh PBL.
      TTK protein and mRNA expression increased in both fresh PBL and T cell blasts
      concurrently with passage of cells through S phase as indicated by [3H]TdR
      incorporation and cell cycle analysis of propidium iodide-stained cells. TTK mRNA
      and protein levels reached a maximum as cells entered the G2 phase of the cell
      cycle. These results were confirmed by cell cycle blockade studies with
      aphidicolin and nocodazole wherein TTK protein levels are not detected in cells
      in G1 and are readily detectable in cells in the S and G2 phases of the cell
      cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254212
TI  - [Methicillin resistance, production of toxic shock syndrome toxin-1 and types of
      enterotoxin, protease and coagulase at vaginal isolates of Staphylococcus
      aureus].
AB  - The vaginal colonization with Staphylococcus aureus, including strains that have
      methicillin resistance and production of toxic shock syndrome toxin-1 (TSST-1),
      enterotoxins and protease was studied in 308 women at the time of delivery.
      Thirty-six of these women were colonized with S. aureus in the vagina. All of the
      isolates were methicillin sensitive S. aureus (MSSA), except one women who had
      both methicillin resistant S. aureus (MRSA) and MSSA. The strains, included MRSA,
      did not elaborate the TSST-1 and produced protease. The distribution of protease
      pattern (types) observed by MSSA strains on standard methods caseinate agar
      plates was type A, 1 strain; type B, 15 strains; type C, 6 strains; type D, 14
      strains. Sixteen of the 36 strains produced non of the enterotoxins and 20
      strains produced enterotoxins and the type distribution was enterotoxin type A, 6
      strains; type B, 10 strains; type C, 1 strain; A and B, 1 strain; A, B and C, 2
      strains. These results provide the possibility of pathogenic S. aureus colonized
      in vagina transmit to neonates at the time of delivery.

PMID- 8254213
TI  - Rapid diagnosis of cytomegalovirus and Pneumocystis carinii pneumonia by using
      the capillary polymerase chain reaction.
AB  - We attempted to detect cytomegalovirus DNA (CMV-DNA) and Pneumocystis carinii DNA
      (P. carinii-DNA) in sputum samples of 18 hematological neoplasm patients with
      pneumonia, using rapid cycle DNA amplification. A thermal cycler based on
      recirculating hot air was used for rapid temperature control of 10-microliters
      samples in this glass capillary tubes. After a total amplification time of 15
      min, the amplified products were electrophoresed on agarose gels and visualized
      with ethidium bromide. In three cases, CMV-DNA was detected at about the time the
      pneumonia occurred. These patients were successfully treated with ganciclovir in
      the early stages of infection and CMV was not detected by the virus culture
      method. In four other cases, P. carinii-DNA was detected in their sputum samples
      but not detected by Grocott staining. These four cases of P. carinii were
      successfully treated with sulfamethoxazole-trimethoprim. For detection of CMV-DNA
      and P. carinii-DNA using the capillary polymerase chain reaction (PCR), a
      different temperature setting base on the primer difference was not necessary.
      Therefore, capillary PCR was performed at the same time for detection of CMV and
      P. carinii. We conclude that capillary PCR amplification is a valuable tool for
      rapid diagnosis and early treatment of pneumonia due to CMV and P. carinii.

PMID- 8254214
TI  - [Morphological changes of Plasmodium-infected red blood cells in thin blood
      smears].
AB  - Malaria is absent in Japan, but about sixty imported cases are reported in a
      year. We think it desirable that all medical care institutions should examine for
      malaria infection promptly. Diagnosis of malaria, in Japan, depends mostly on the
      examination of thin blood smears stained by Giemsa. However, we sometimes find
      atypical changes of infected red blood cells, especially in their size. It was
      also presumed that infected red cells may differ in their size and other
      morphology by their geographical origin. The present study was designed to
      investigate the influences of malaria infection on the morphology of host red
      cells. Thin blood smear samples from the cases of a single species plasmodial
      infection with epidemiological circumstances were chosen for this investigation
      from the specimens which we examined in our laboratory. Cases with a history of
      chemoprophylactic or chemotherapeutic use within 1 month prior to the blood
      examination were excluded. Cases were classified according to species of the
      infected parasites and the geographical origin; Africa, South-East Asia, and
      Western Pacific. The distribution of red cell diameters and the ratio of maximum
      diameter to minimum diameter were determined on blood smears using oil immersion
      lens. Measurement was completed with 20 or 30 infected red cells for each
      developmental stage of the parasites and 30 non-infected red cells per slide. The
      presence of Schuffner's dots was observed on blood smears from vivax or ovale
      malaria patients. We examined also for Maurer's dots and fimbriated margin of red
      cells on falciparum and ovale malaria specimens respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8254215
TI  - [A clinical study of chronic lower respiratory tract infections with Pseudomonas
      aeruginosa by transtracheal aspiration].
AB  - We investigated the yearly changes of the incidence of Pseudomonas aeruginosa (P.
      aeruginosa) isolated from chronic lower respiratory tract infections (CLRTI), and
      also performed a clinical study on CLRTI with P. aeruginosa by transtracheal
      aspiration (TTA) to clarify the recent trend of P. aeruginosa infection in CLRTI
      and the predisposing clinical factors to the acute exacerbation. The isolation
      rate of P. aeruginosa among the total isolated bacteria in CLRTI between December
      1978 and March 1983 was 8.4%, but it increased to 23.1% between April 1988 and
      March 1993. In 69 episodes (40 cases) of P. aeruginosa isolated from CLRTI
      between April 1983 and March 1993, monomicrobial infections of P. aeruginosa were
      42 episodes (60.9%) and polymicrobial infections were 27 episodes (39.1%). When
      the diseases were classified into acute exacerbated and non-exacerbated phases,
      polymicrobial infections were seen more in the former phase, and the principal
      organisms detected with P. aeruginosa were Haemophilus influenzae and
      Streptococcus pneumoniae. In the acute exacerbated cases, predisposing conditions
      concerning the exacerbation were divided into four patterns: 1. polymicrobial
      infections with H. influenzae or S. pneumoniae, 2. after acute upper respiratory
      tract infections due to viral superinfection, 3. early phase from bacterial
      replacement by P. aeruginosa, 4. immunocompromised states such as adrenal
      corticosteroid administration or systemic underlying diseases. These results
      suggest that the importance of P. aeruginosa in CLRTI is increasing year by year
      and we must pay attention to the fact that P. aeruginosa alone may also cause
      acute exacerbation in the latter 2 patterns of the condition.

PMID- 8254216
TI  - [Studies on the usefulness of saliva for detection of antibodies to HIV-1].
AB  - It has been reported that antibodies to HIV-1 could be detected in saliva of
      patients with AIDS. We studied whether saliva is potentially useful for screening
      of HIV-1 infected persons. Pairs of serum and saliva were collected from both 19
      HIV-1 seropositive outpatients (CDC type, II:15, III:1, IV:3) of AIDS clinic in
      our hospital and 4 controls. Multiple saliva collection was done from
      seropositives periodically for 8 months after the first sampling. Serum and
      saliva were tested with ELISA and Western blot (WB) methods by using kits of
      diagnostics Pasteur (ELAVIA MIXT and LAV Blot-1). All pairs of serum and saliva
      from controls were clearly negative by ELISA. Nineteen sera of proven
      seropositive cases and paired 18 saliva samples were confirmed to be positive in
      ELISA test employed, but O.D. value of 1 saliva sample was below the cut-off
      level. However, in the follow-up study, samples taken from the same individuals
      after the first sampling showed positive results. Forty-seven saliva samples from
      seropositives were served for the WB test. Clearly positive bands were observed
      in 43 samples. In each of the remaining 5 samples, the final decision was
      "indeterminate", although a strong reactive band was observed at GP-160. The
      results mentioned above suggested that saliva was useful for screening of
      antibodies to HIV-1 in epidemiological studies, though it is necessary to improve
      the sensitivity of ELISA and WB for tests of saliva.

PMID- 8254217
TI  - [An animal model of Pneumocystis carinii pneumonia and therapeutic efficacy of
      interferon-gamma in this model].
AB  - To evaluate the efficacy of drugs for treatment, we tried to make an animal model
      of Pneumocystis carinii (P. carinii) pneumonia. Specific pathogen free (SPF) rats
      immunosuppressed with corticosteroid were intratracheally inoculated with P.
      carinii. Six weeks after the inoculation, the lung sections of infected rat lung
      showed increased numbers of P. carinii in the alveoli and thickening of alveolar
      septa with mononuclear cell infiltration. From 7 to 9 weeks after inoculation,
      the intensity of infection became more severe, and some rats died at this period.
      Then, to evaluate drug efficacy in this model, we finished the drug therapy by
      the 6th week and used the number of P. carinii in the lung and the inflammation
      score as an indicator of drug efficacy. In this P. carinii pneumonia animal
      model, both sulfamethoxazole-trimethoprim clinically established anti P. carinii
      drug and interferon-gamma which is one of the lymphokines mainly produced by T
      lymphocytes indicated therapeutic and synergistic efficacy against P. carinii
      pneumonia.

PMID- 8254218
TI  - [An epidemiological study on chronicity and incidence of hepatocellular carcinoma
      in the sequence of epidemic hepatitis].
AB  - From November 1951 to 1954, 416 patients in Kumayama Town, Okayama Prefecture,
      suffered from epidemic hepatitis, so-called "Kumayama Hepatitis". The mortality
      rate was 13.98% in the first one year, and the rate of progress to chronic
      hepatitis after 10 years was 24.6%. In the present study surveyed in 1991, 720
      residents in this area had 13.6% positive anti-HCV (C100-3), significantly higher
      than in control areas. The rate of positive anti-HBs and abnormal liver functions
      in the subjects with positive anti-HCV was 42.9% and 40.8%, respectively. In 29
      patients with clinically typical "Kumayama Hepatitis", the positivity rate of
      anti-HA IgG, anti-HBs, and anti-HCV, and the prevalence of abnormal liver
      function was 82.8%, 41.4%, 34.5%, and 10.3%, respectively. In conclusion, it is
      suggested that the hepatitis epidemic in Kumayama Town was caused by HAV and
      superinfected by HCV and/or HBV, then its clinical manifestations became
      complicated.

PMID- 8254219
TI  - Nasal carriers of Staphylococcus aureus among healthy individuals.
AB  - Staphylococcus aureus and Staphylococcus spp. were isolated from healthy students
      and their drug resistance was investigated. S. aureus was isolated from 17 of 70
      persons (24.3%). Fourteen strains of 22 isolates of S. aureus were ampicillin
      resistant. Two strains each were cefmetazole-resistant and gentamicin-resistant.
      None of the strains was found to be methicillin-resistant. Compared with the
      strains isolated from the hospital ward environment, S. aureus in healthy
      individuals was relatively sensitive to antibiotics.

PMID- 8254220
TI  - [Studies on effects of new quinolones on superoxide production--with special
      reference to NADPH oxidase].
AB  - The effects of nalidixic acid (NA) and various new quinolones, such as
      norfloxacin (NFLX), ofloxacin (OFLX), tosufloxacin (TFLX), lomefloxacin (LFLX)
      and temafloxacin (TMFX), on the superoxide production of human neutrophil NADPH
      oxidase were investigated. In their therapeutic concentrations, NA, NFLX and OFLX
      had no significant effects on superoxide generation of NADPH oxidase. However,
      TFLX, LFLX and TMFX increased superoxide production by about 130 percent. Fifty
      microM NA increased superoxide production by 130 percent. Recently, it has been
      reported that NA and the new quinolones have toxic side effects on the central
      nervous system. In this report, relationships between toxic side effects of the
      new quinolones and superoxide production were discussed.

PMID- 8254221
TI  - The immune system victorious: selective preservation of self.
AB  - How the body successfully distinguishes its own tissue cells from those that are
      foreign and genetically nonidentical to it has been a focus of much research.
      Clonal deletion maintains that immune system cells with the potential to injure
      self constituents are eliminated during development, thereby neutralizing their
      capacity to induce self injury. Selected self-reactive maturing T cell clones
      undergo deletion in the thymus. A two-step selection process affects immature T
      cells that enter the thymus. Positive selection makes certain that all surviving
      cells are able to identify major histocompatibility complex (MHC) proteins
      present on all body cells. These MHC proteins interact with antigens and present
      them to T lymphocytes. Negative selection is essential for self-tolerance. It
      eliminates potentially injurious self-reactive T cells by placing them in contact
      with a mixture of self antigens in the thymus. Clonal anergy might act together
      with clonal deletion to maintain self tolerance. Self-reactive T cells in the
      blood of healthy subjects could represent cells whose affinities for antigen are
      too weak to initiate an immunologic disease. The fate of T cells reacting to a
      specific antigen has been traced in transgenic mice. Class I MHC molecules
      present peptides manufactured within the cell, whereas class II MHC molecules
      present peptides from extracellular proteins. Interaction of a T cell receptor
      with its homologous antigen associated with MHC molecules leads to proliferation
      of that T cell in the presence of costimulatory signals. Investigations
      elucidating the role of T cell receptors, MHC molecules and antigen peptides in
      self-nonself discrimination are discussed. The article concludes with an
      introductory summary of the remaining articles in the issue that address selected
      topics in self-nonself discrimination.

PMID- 8254222
TI  - Self-nonself discrimination and tolerance in T and B lymphocytes.
AB  - The immune system must not only fight off infections, but also ensure that it
      does not react against its own body tissues. Since clones of lymphocytes have
      predetermined reactivities, some will be self-reactive and have the potential to
      cause damage. They should therefore be neutralized in some way. In a system as
      complex and important as that governing self-tolerance, many mechanisms must
      exist to neutralize autoaggressive lymphocytes. They may be classified under two
      main groups. In one the tolerant state arises from the physical or functional
      silencing of potentially autoaggressive lymphocytes after antigen encounter. This
      may involve clonal deletion, clonal abortion or clonal anergy. In the second,
      regulatory mechanisms of the immune system itself may hold autoreactive
      lymphocytes in check, for example through the operation of idiotypic network
      interactions and the action of specialized suppressor cells. Much evidence has
      accumulated for the physical deletion of autoreactive T cells as they mature in
      the thymus. The fate of any that escape thymus censorship has been the subject of
      recent research and is discussed here. Under certain conditions, self-tolerance
      must also be imposed at the B-cell level to prevent the production of potentially
      damaging autoantibodies. Although the mechanisms which silence self-reactive
      lymphocytes are very efficient, self-tolerance can break down, and autoimmunity
      will thus ensue. The main factors responsible for this are briefly described
      here.

PMID- 8254223
TI  - Cellular basis of T-cell autoreactivity in autoimmune diseases.
AB  - There is no doubt that T cells play a key role in the pathogenesis of autoimmune
      diseases (AD) both as effector and regulatory cells. Despite spectacular progress
      in the understanding of natural tolerance to self, owing particularly to
      transgenic technology, important questions remain open regarding the pathogenesis
      of AD, the conditions favoring the transition from benign or 'physiological'
      autoimmunity to deleterious autoimmunity, and the precise effector mechanisms.
      This review on the cellular basis of T-cell-mediated AD begins with an
      enumeration of the main arguments in favor of direct T-cell involvement, special
      emphasis being given to two animal models which have been most extensively
      investigated: experimental allergic encephalomyelitis, and the nonobese diabetic
      mouse. The question as to whether pathogenic T cells use a restricted repertoire
      of V beta genes is examined in the context of these two models. From here we
      proceed to an evaluation of the mechanisms of onset of AD, discussing both
      extrinsic and intrinsic factors responsible for the breakdown in T-cell tolerance
      and reviewing the arguments in favor of suppressor T cells being actively
      involved in the prevention of autoimmunity. The last two sections are devoted to
      the effector mechanisms responsible for tissue injury in organ-specific AD and to
      T-cell-directed therapeutic interventions, respectively. We discuss the two main
      pathogenic hypotheses based on direct intervention of cytotoxic T cells or
      indirect involvement of inflammatory cytokines and macrophages, and evaluate the
      importance of ecotaxis in leading autoreactive T cells to the site of injury. We
      conclude on a brief and nonexhaustive list of strategies aimed at selectively
      neutralizing potentially harmful T cells.

PMID- 8254224
TI  - T cell repertoire and autoimmune diseases.
AB  - Self-reactivity and autoimmunity are processes related to the breakage of self
      tolerance that can be distinguished by their different clinical outcome and are
      widely accepted cornerstones of immunology. The finding that several potentially
      autoaggressive cells contribute to the repertoire of healthy individuals has
      stimulated a great deal of experimental work aimed at understanding the
      mechanisms that prevent autoimmune pathology. In this review we will consider the
      basic principles, and our present knowledge of the rules that preside over the
      interplay of the immune system with self-components. One viewpoint stresses the
      importance of major histocompatibility complex (MHC) and non-MHC genes in
      determining genetic predisposition to develop autoimmune phenomena. At a
      different level there is a strong interest in understanding the mechanisms of
      processing and presentation of self antigens, especially during ontogeny. Another
      topic of major interest concerns the interaction between MHC genes and the T cell
      receptor (TcR) complex as well as the identification of TcR V genes that are
      preferentially expressed by autoimmune T cells. All of these aspects are
      evaluated in the context of tolerance based on deletion and anergy. Finally we
      will propose a general model of autoimmunity based on the most recent findings
      concerning the biological activity of exogenous superantigens.

PMID- 8254226
TI  - The antitumor immune response as a problem of self-nonself discrimination:
      implications for immunotherapy.
AB  - Much evidence now exists that tumors possess specific antigens recognizable by T
      cells. The goal of immunotherapy is to break tolerance to these antigens while
      preserving self-tolerance. Recently, newer approaches have been developed in
      animal systems that modify tumor cells genetically so that they express new
      antigens or secrete certain cytokines. Engineering tumor cells to secrete
      cytokines in a paracrine fashion can induce powerful local cytokine effects
      which, in addition to inducing local inflammation, can alter the presentation of
      tumor antigens or the activation of tumor-antigen-specific T lymphocytes,
      resulting in systemic antitumor immunity.

PMID- 8254227
TI  - Hydra: a C-language environment for real-time DOS multitasking at the bedside.
AB  - Patient monitoring at the bedside is an inherently parallel job, best handled by
      multiple individual tasks running concurrently. Cost and diffusion considerations
      strongly favor the use of PC's at the bedside, but their most widespread
      operating system, DOS, is not built for multitasking. Hence, a software platform
      in C language has been prepared, allowing the intermediate programmer to easily
      write independent modules which will then run simultaneously without conflicts.
      Such a platform aims at allowing effortless sharing of data among concurrently
      running processes, while providing strong insulation between tasks, enough to
      allow multiple copies of any one task to run simultaneously unknown to each
      other. A cooperative, memory sharing multitasking paradigm has been chosen, which
      offers fine granularity of timeslicing and low execution overhead at the price of
      some loss in generality of design. Speed, data exchange capability and number of
      stackable windows are greater than with commercial packages like Windows or
      LabWindows. Dynamical reprioritization of tasks is built in, allowing the
      computerized monitor to focus its attention and resources on urgent tasks.

PMID- 8254225
TI  - The self and the nonself: immunorecognition and immunologic functions.
AB  - For almost a century self-nonself discrimination has been considered the driving
      force of the immune system and the dogma of self-tolerance (horror autotoxicus)
      the essential issue for understanding protective immunity and pathologic
      autoreactivity. This classical picture has been recently challenged by the
      discovery that the immune system is influenced by internal activation (amor
      autocognitus) and autoreactive clones are both present and activated in healthy
      individuals. Central to the concepts of reactivity and tolerance, in other terms,
      to physiology and pathology, is the analysis of structures involved in
      immunorecognition and as they contribute to the outcome of the immune response.
      The capacity of the immune system to recognize nonself structures and eventually
      react to them developed during evolution probably before the generation of
      clonally distributed antigen receptors. The high level of autoreactivity that
      characterizes the immune system seems to suggest that immunocompetent cells never
      learned to ignore the self, but rather that, sometime during evolution, they
      specialized in the function of self-identification, one of the most basic
      activities of all living cells. Autoimmune diseases would result from a
      pathologic deviation of a physiologic function, just as many other diseases do.

PMID- 8254228
TI  - Monitoring intensive care unit performance using statistical quality control
      charts.
AB  - This paper discusses results of a study in which mortality rates and APACHE II
      severity of illness scores of Intensive Care Unit (ICU) patients were monitored
      for a five-year period (1986-1990) using statistical quality control charts. The
      purpose of the study was to determine whether severity of illness of patients and
      mortality rates had changed significantly over this time horizon. The results
      show that the Intensive Care Unit process is stable and in statistical control.
      There is no apparent trend in the severity of illness scores nor mortality rates
      measured both at ten days and six months from the last ICU admission. Quality
      control charts, which have been used extensively to detect changes in industrial
      processes on a short term basis, provide a simple method of monitoring the ICU
      process over an extended time horizon.

PMID- 8254229
TI  - Choices that have to be made by a doctor.
AB  - The Author analyses the technical and ethical choices the doctor who works in the
      Intensive Care Unit continually has to make when treating patients. Generally the
      doctor does not accept the concept that the available economic resources are not
      infinite, in that he sees himself as the patient's advocate. The ethical problem
      of whether or not to treat a given patient arises before the technical problem.
      Making a choice, it is necessary to know what benefits will derive from a given
      treatment in a certain ward and how successful a given operation will be. The
      doctor must evaluate the management costs but must also be the custodian of
      community funds.

PMID- 8254230
TI  - Therapeutic process formalization in the treatment of respiratory failure in
      infants.
AB  - The model described formalizes the therapeutic process developed in the Pediatric
      Intensive Care Unit (PICU) of Merate's Hospital as a support of medical decisions
      and as a continuous control of the adequacy of the ventilatory therapy. Causal
      and temporal structure of the keypoints of the treatment are represented by Petri
      Nets. The model could be utilised in different pathologies and for different
      clinical approach giving a meaningful organizational impact.

PMID- 8254231
TI  - Assessment of the value and pattern of use of a target controlled propofol
      infusion system.
AB  - Thirty one anaesthetists were supplied with a pharmacokinetic based target
      controlled propofol infusion system for evaluation. Twenty seven of 30 replies to
      a questionnaire sent to them indicated that the system had changed their use of
      propofol for maintenance of anaesthesia. The main reasons were greater ease of
      use and more confidence regarding the predictability of anaesthetic effects
      compared with manually controlled infusion. Data obtained from 770 patients
      anaesthetised with the system were analysed. The median maximum target
      concentration selected was 6.6 micrograms/ml. Younger patients (18-35 yr)
      required significantly greater target concentrations than older patients (65-80
      yr). The mean time during which the system was in maintenance mode, when the
      predicted blood concentration of propofol was held constant for at least one
      minute, was 26.1 minutes. The median number of alterations in propofol
      concentration was 6. The target controlled infusion system provided an
      inexpensive and acceptable method of delivering intravenous anaesthesia.

PMID- 8254232
TI  - Heart rate variability and severe brain damage: preliminary data.
AB  - Severe brain damage may cause alterations of cardiovascular function: heart rate,
      particularly, require the integrity of the vagal, sympathetic and central nervous
      systems. We studied brain-heart functional relation and neurovegetative
      modulation by spectral analysis of heart rate variability (HRV). This technique
      allows separate evaluation of the sympathetic and vagal components of heart rate
      modulation. In order to correlate changes in HRV with brain damage, we performed
      45 recordings in 6 patients (5/1 M/F) by means of autoregressive analysis (AAR).
      All patients were admitted to the ICU for severe brain damage (anoxic, traumatic
      or vascular). In 4 patients clinical outcome was brain death, in 2 permanent
      vegetative status. Two different patterns were found: one in patients with brain
      death, the other in patients with vegetative status. The small number of patients
      does not allow definitive conclusions from collected data, but that application
      of spectral analysis of HRV seems to be a useful monitoring of brain damage
      subjects.

PMID- 8254233
TI  - Patterns of chronic granulomatous disease.
AB  - We report the clinical course of an adult patient with chronic granulomatous
      disease, an inherited disorder of neutrophil function that is generally limited
      to the pediatric population. The biochemical and functional disorders of the
      neutrophil in chronic granulomatous disease are examined. The mode of inheritance
      and expression of this disease is profiled to aid the clinician who must consider
      this diagnosis in the adult patient with recurrent infections.

PMID- 8254234
TI  - Cerebral hyperperfusion syndrome: an etiology of seizures following carotid
      endarterectomy.
AB  - Cerebral hyperperfusion syndrome after carotid endarterectomy is an uncommon but
      distressing complication. Findings in nearly all these patients include the
      presence of ipsilateral high-grade carotid artery stenosis, postoperative
      ipsilateral headache followed by seizures, and transient neurologic deficits. It
      appears to be caused by the loss of autoregulation within the brain, usually
      occurring between 5 and 7 days postoperatively.

PMID- 8254235
TI  - Invasive aspergillosis of the central nervous system.
AB  - Advancing technology permits aggressive medical interventions that are often
      lifesaving, yet place the patient's immune system in temporary jeopardy. During
      the interval of immunocompromise, physicians must maintain vigilance for
      opportunistic infection by saprophytic organisms such as Aspergillus. Although
      the lung is the most common site of infection by this fungus, subsequent
      hematogenous dissemination with central nervous system involvement may occur.
      Currently, the majority of Aspergillus infections of the central nervous system
      remain unrecognized until the patient's demise. The clinical and pathological
      features of aspergillosis of the central nervous system are reviewed in order to
      promote earlier diagnosis and treatment.

PMID- 8254236
TI  - "Kentucky Care" plan.

PMID- 8254237
TI  - Newborn immunizations.

PMID- 8254238
TI  - [Carotid surgery. Assessment and current problems].
AB  - Every year in France, approximately 12,000 strokes are due to stenosis of an
      extracranial internal carotid artery. One third of these patients are dead and
      one third have disabling sequelae at 6 months follow up, emphasizing the need for
      prophylactic therapy. The efficacy of antiaggregants and the value of correction
      of risk factors have been proven for a decade or more, whereas carotid artery
      surgery has for a long time been a subject for debate because of its
      perioperative complications and the lack of consensus on its indications.
      Happily, several recent multicenter studies have provided positive evidence of
      its value. After a transient ischemic accident or mild stroke, patients with a
      stenosis of more than 70% should be operated upon, in the absence of any local or
      general contraindication and if the surgical team has a record of a less than 5%
      cumulated mortality and neurologic morbidity. For asymptomatic severe stenotic
      lesions, it appears justified to operate on those occluding by more than 80%, in
      patients presenting the same characteristics and if the surgical team's incidence
      of complications is less than 3%. Although arguments exist for operating upon a
      severe carotid artery stenosis associated with vertebrobasilar insufficiency or
      severe stroke without major cerebral impairment, these indications have not been
      evaluated by multicenter trials and each case should be treated individually.

PMID- 8254239
TI  - [Carotid stenoses. Non-invasive exploration].
AB  - Doppler flowmeter and ultrasound imaging techniques, currently associated
      (duplex), have made important contributions to the simple and early non invasive
      diagnosis of carotid stenosis lesions in the cervical region for more than 20
      years. These exploratory methods are reliable when a significant degree of
      stenosis (greater than about 60%) exists. Moderate degrees of stenoses or plaques
      are evaluated morphologically, calcifications and ulcerations being enhanced by
      staining techniques. But the evaluations have not really demonstrated exact
      correlations between anatomicopathologic and ultrasound images. The intracranial
      arteries and the circle of Willis are explored indirectly during the cervical
      examination by cautious compressive maneuvers or directly by trans-cranial
      Doppler. Whereas angiography competes with ultrasound imaging as a standard
      examination in the neck region, it nevertheless remains effective for the study
      of the intracranial arteries. Newer techniques, such as high-field MRI
      angiography, tridimensional ultrasonography or ultrasound recording of vascular
      flow rate without Doppler, will doubtlessly transform the diagnosis of
      symptomatic or asymptomatic carotid stenosis. From the strategic point of view,
      ultrasound imaging techniques will retain their role of a decisional pivot, since
      they are simple to use and are of very wide accessibility to competent vascular
      physicians in the context of an organized care network.

PMID- 8254240
TI  - [Evolution of symptomatic carotid stenoses under medical treatment].
AB  - Data from the 2 major studies (ECST and NASCET) carried out to evaluate surgery
      of symptomatic carotid artery stenosis provided more information on the evolution
      (during medical treatment) of these lesions than all previous work. The essential
      risk, that of a cerebral infarction homolateral to the stenosis, is closely
      related to the degree of stenosis; for occlusions greater than 70% it was 5%
      annually in the ECST and 13% in the NASCET, more severe occlusions being treated
      in the latter study. Inversely, it was only 0.5% annually for stenoses involving
      less than 30% (ECST). For occlusions of between 30 and 70%, the risk has not yet
      been determined exactly, since the 2 studies are ongoing, but everything suggests
      that the risk is related to the degree of stenosis for this range also. Factors
      increasing this risk include: the cerebral site--and not only retinal--of the
      initial stenosed carotid, the ulcerative nature of the stenosis, the existence of
      contralateral carotid occlusion and the presence of vascular risk factors.
      Therapy is dependent on the evaluation of total risk factors, surgery being
      indicated increasingly as there is the greater high risk of stenosis. Surgery is
      then additional to medical treatment of vascular risk factors, mainly
      hypertension and antithrombotic therapy: generally aspirin and perhaps
      Ticlopidine.

PMID- 8254241
TI  - Symptomatic patients: the European Carotid Surgery Trial (ECST).
AB  - The European Carotid Surgery Trial (ECST) is an ongoing randomised trial of
      immediate carotid endarterectomy vs non-surgery in symptomatic patients with
      recent and mild carotid territory ischaemic events. So far it is become clear
      that the risk of the operation is--in general--worth taking in patients with
      "severe" stenosis (> 70% of the proximal internal carotid artery diameter) but
      not in patients with "mild" stenosis (0-29%). The balance of risk vs benefit in
      patients with "moderate" stenosis (30-69%) is still unclear und recruitment of
      such patients continues. All patients are still being followed up to assess the
      durability of any benefit of surgery and to develop prognostic models to predict
      the risk of ipsilateral ischemic stroke in the no-surgery patients. Also, further
      studies are being done to investigate the best method of measuring the amount of
      disease at the carotid bifurcation.

PMID- 8254242
TI  - Status report on the North American symptomatic carotid surgery trial.
AB  - NASCET randomized patients with focal symptoms related to arteriosclerotic
      disease manifest by transient or nondisabling ischemic events in the ipsilateral
      hemisphere or retina. Patients were randomly assigned to receive best medical
      care including aspirin when tolerated and control of manageable risk factors or
      the same medical program to which carotid endarterectomy was added. Patients were
      stratified into those with arteriographic stenosis of 70% or greater or into the
      moderate category of less than 70% stenosis. Interim analyses after three years
      disclosed for patients with 70% or more stenosis a clear benefit from surgery.
      Below 70% there was no indication of benefit nor harm. The entry of patients with
      severe disease was stopped and the result published. At two years after surgery,
      17 strokes are prevented for every 100 patients submitted to the procedure with
      severe stenosis. It can also be stated that the functional status of the patients
      in the surgical cohort exceeded that in the patients assigned to medicine.
      Subgroup analyses noted that: the risk experienced by medical patients with
      retinal events is only one-third for those with hemisphere events. A definite
      ulcerative lesion nearly doubles the risk. Age is an important risk factor but
      surgery benefits those in the later as in the younger decades. Contralateral
      stenosis adds only slightly to the risk of stroke whereas contralateral occlusion
      quadruples the risk. Surgical benefit is present despite contralateral occlusion.
      Silent brain infarctions in CT examinations added to the risk in the medical
      group compared to those without this phenomenon. Surgery benefited both of these
      subgroups equally.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254243
TI  - [Asymptomatic carotid stenoses. Analysis of randomized studies].
AB  - Results of recent randomized clinical trials in patients with asymptomatic
      carotid artery stenosis have progressively tended towards a more surgical than
      medical attitude to treatment. Interim results of the Veterans Administration
      study of 444 patients randomly allocated to receive either aspirin (233 cases) or
      surgery (211 cases) showed the percentage of vascular accidents and postoperative
      mortality to be 2.4% and 1.9% respectively in the surgical group, a marked
      reduction when compared with the 5% neurologic events reported in the medical
      group. In contrast, results of the Casanova Study, an equally randomized trial of
      410 patients, 344 of whom underwent carotid endarterectomy, failed to demonstrate
      a significant difference in neurologic events or mortality between the two
      groups, although these were not homogeneous. Finally, the randomized French study
      (AURC) in 230 patients (135 operated upon and 109 treated medically with aspirin)
      showed a reduction in neurologic accidents in the surgical group, significant
      after a follow up of about 45 months. This tendency towards a surgical approach
      implies a low surgical morbidity/mortality, now possible due to local and
      regional plexus anesthesia monitoring, which carries a morbidity of less than 2%
      and a practically inexistent mortality.

PMID- 8254244
TI  - [Influence of coronary disease on the results of carotid surgery].
AB  - The object of this retrospective (case-control) study of 513 carotid artery
      operations in 471 patients was to evaluate whether the presence of coronary
      artery disease at the time the decision to operate was taken, influence the
      prognosis of patients operated upon for stenosis of a carotid artery. Three
      groups were constituted and compared; no coronary artery disease (NC), stable
      coronary artery disease (CS) and unstable coronary artery disease (CI). Operative
      mortality was 1% (NC), 5% (CS) and 9% (CI) respectively (p < 0.001). The rate of
      neurologic deficits was 1.3% (NC), 2.4% (CS) and 3.1% (CI), and the 5 year
      actuarial survival rate 83% (NC), 78% (CS) and 63% (CI) (p = 0.040 by the Log
      Rank test). Premature deaths were due to cardiac and neurologic causes. In the
      patients with coronary disease, local and regional anesthesia was followed by 0%
      mortality whereas the rate was 3% (CS) and 13% (CI) (p < 0.001) after general
      anesthesia. The cause of delayed death was determined accurately in 50% of cases;
      it was cardiac in 25% (NC) and 70% in patients with coronary disease. Results of
      the present study confirm that the presence of coronary disease has an adverse
      effect on the immediate and long term prognosis for patients undergoing coronary
      artery surgery, and demonstrate that the operative risk can be significantly
      reduced by the use of local and regional anesthesia. Long term close cardiology
      surveillance is justified, particularly if signs of coronary disease are noted
      perioperatively.

PMID- 8254245
TI  - [Coronary occlusive disease and carotid stenosis].
AB  - In around 2.5% of patients with coronary artery diseases (CAOD), considerably
      occlusive changes in carotid arteries were also registered at the same time. In
      the period from March 1982 to February 15, 1993, at the University Clinic of
      Cardiovascular surgery in Novi Sad, a total of 5,701 patients underwent
      aortocoronary by-pass (ACBG). In 137 (2.4%) patients an additionally
      endarterectomy of carotid arteries (EAC) were also performed. Bad left ventricle
      function (EF < 30%) was registered in 30 pts (22%). Endarterectomy on one or more
      arteries had to be performed in 45% patients because diffuse and distal occlusive
      changes. Two stage operations were performed in 62 cases. Three stages operations
      (bilat. EAC) in 24 and simultaneous in 51. Operative mortality (30 days) was
      registered in 5 (3%) pts. Neurologic deficit (ND) happened in two (1.4%) pts, TIA
      in 3 pt (2.2%). Comparing our results in simultaneous and stage procedure,
      operative risk is higher in simultaneous operations, and only in case of unstable
      angina we prefer simultaneous operations.

PMID- 8254246
TI  - Severe bilateral carotid stenosis.
AB  - An analysis of the relevant data from the Veterans Affairs Cooperative Study
      Group in asymptomatic patients, showed that 26 of the 32 ipsilateral strokes
      occurred during the first two years of clinical follow-up. Furthermore, as
      observed in the medical group, half the neurologic outcome events were strokes
      and were not preceded by transient ischemic attacks. In the North American
      Symptomatic Carotid Endarterectomy Trial over a 2-year period, 45 percent of
      those with occlusion had a stroke compared to 15 percent in the surgical group.
      These data dispel the traditionally held view that patients with severe
      contralateral disease should not be subjected to surgery. However, the referral
      of patients to centers capable of low rates of surgical complications is
      essential in a plan that includes carotid endarterectomy with optimal medical
      management.

PMID- 8254247
TI  - [Carotid stenosis associated with contralateral carotid occlusion].
AB  - Carotid surgery in patients with carotid stenosis and contralateral occlusion is
      generally followed by a higher operative morbidity and mortality-rate than
      patients with monolateral stenosis. To verify our experience, the records of 167
      patients affected with internal carotid stenosis with contralateral occlusion
      operated on between 1978-1991 were reviewed. They were 139 males and 28 females
      with a mean age of 62.3 years, and represent the 16% of the patients operated on
      for carotid lesion in the same time period. The indications for surgery were TIA
      or RIND in 52 patients, minor stroke or stroke in 9, non hemispheric symptoms in
      19; 22 patients were asymptomatic, and 75 presented symptoms unrelated to the
      operated stenosis. The operative morbidity and mortality-rate of the whole sample
      were: stroke-rate 4.8%, mortality-rate 3% and cumulative stroke + mortality-rate
      5.4%. In particular the operative risk was higher in patients operated on for
      stroke or for vertebro-basilar symptoms, while patients with reversible symptoms
      and asymptomatic patients had a significant lower stroke-rate both in the post
      operative period and in the follow-up (p < 0.02). Patients operated on for
      completely asymptomatic lesions and for contralateral borderline symptoms had no
      operative symptoms. Relationships between operative complications and pre or per
      operative monitoring have been analyzed; our results suggest a more extensive use
      of intraluminal shunt and an operation under general anaesthesia in patients with
      ischemic areas shown by a pre-operative SPECT or with a cerebral infarct even if
      SPECT monitoring does not suggest its use.

PMID- 8254248
TI  - [Atheromatous pseudo-occlusive stenosis of the internal carotid].
AB  - Pseudo-occlusion of the internal carotid artery is defined as an angiographically
      occluded but anatomically patent artery. Between january 1980 and december 1990,
      14 cases were diagnosed in our institution. Preoperative Doppler examination of
      the internal carotid artery suggested almost complete thrombosis in 11 patients
      and occlusion in 3. The angiographic appearance suggested internal carotid
      occlusion in all but the presence of the slim sign was in favor of a patent
      artery. All 14 patients underwent surgery. There were no postoperative deaths;
      one patient presented an ipsilateral TIA post operatively; 3 others presented an
      ipsilateral TIA after 2, 16 and 30 months respectively. All carotid arteries were
      found to be patent. The frequency of pseudo-occlusion of the internal carotid
      artery is probably underestimated. It must be kept in mind whenever an apparently
      occluded internal carotid continues to be symptomatic. Diagnosis is based on
      comparative analysis of Doppler examination and angiographic findings. Surgery is
      indicated whenever doubt persists.

PMID- 8254249
TI  - Blood brain barrier breaking. Is still an absolute contraindication to early
      surgical reperfusion of the brain?
AB  - In the early treatment of the patients with cerebrovascular insufficiency due to
      internal carotid artery stenosis, the presence of a cerebral infarct and
      especially the blood brain barrier breaking (BBB) are considered by many as a
      contraindication to early reperfusion by carotid endarterectomy (CEA). Generally,
      it has been recommended to differ the operation at least for 4-6 weeks because of
      the high risk to convert an ischemic infarct into an hemorrhagic one. On the
      other hand, because unfavorable natural history has been reported as for the
      progressing unstable neurological deficit as for the minor recent strokes,
      respectively by Millikan and Dosik, it seem to be justified a more aggressive
      management with the aim of: 1) eliminating the stenosis as embolic source of
      emboli; 2) obtaining early brain reperfusion to increase the probability of good
      recovery. Some previous experiences reported in the literature demonstrated
      satisfactory results of early reperfusion even in presence of BBB. The Authors
      present 4 cases of early CEA in patients with BBB. After the CT scan the patients
      have been submitted preoperatively to non invasive tests (duplex scanning and
      transcranial Doppler sonography) to assess the presence of the internal carotid
      artery stenosis and the viability of the intracranial cerebral arteries with
      special regard to the middle cerebral artery. All the patients underwent CEA in
      loco-regional anesthesia and particularly systemic blood pressure was carefully
      monitored and any hypertensive status was early corrected by prompt
      antihypertensive therapy (i.v. nitrates and or calcium blocking agents).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8254251
TI  - [Is age a limiting factor for carotid surgery?].
AB  - To evaluate the role of carotid surgery in elderly patients 75 years and older,
      we reviewed 912 carotid endarterectomies performed on 806 patients between 1987
      and 1990. There were 151 patients (19% of the whole series) aged 75 years and
      older (160 endarterectomies, group A), including 29 octogenarians, vs 655
      patients under 75 years of age (group B). There were more women in the elderly
      age group (44%) than in the younger one (38%). Symptoms, risk factors, operative
      outcome and follow up data of the two groups were compared. The risk profile was
      similar for the two age groups, with exception for coronary heart disease, less
      frequent in the older patient group (25% had previous infarction vs 44%).
      Indication for carotid endarterectomy was different in the two age groups: 41% of
      group A underwent prophylactic thrombendarterectomy for high degree stenosis,
      while only 30% of group B had asymptomatic carotid disease. In group A, 6% of the
      patients had carotid endarterectomy after recovering from a mild stroke, vs 2% in
      group B. Angiography revealed bilateral carotid disease in 59% of the group A
      patients (including 15% with contralateral occlusion) vs 40% in group B.
      Operative mortality was 1.5% for the younger age group vs 2.5% for the older age
      group. The cause of death was cardiac in 60%. A follow up is available for all
      patients who benefited carotid endarterectomy since 1976, including 180 patients
      aged 75 years or older.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254250
TI  - Surgical management of intraluminal carotid thrombi.
AB  - The most suitable treatment for intraluminal carotid thrombi remains still a much
      debated question. Some authors have reported a lower morbidity in patients
      treated with anticoagulant or antiplatelet therapy; on the other side, urgent or
      delayed surgery is burdened with a high risk of perioperative stroke. Over 11
      years (october 1981-november 1992) 602 surgical revascularizations on epi-aortic
      vessels have been performed at Vascular Surgery Unit of Udine Regional Hospital.
      Only 2 cases of intraluminal carotid thrombi were observed: both fulfilled the
      angiographic requirements for endovasal filling defect, surrounded by contrast
      medium, adherent to posterior wall and extending to distal internal carotid
      artery. First patient suffered a TIA 20 days before surgery, the second one a
      previous major stroke contralateral to the thrombus. The former was given
      preoperatively a medical anticoagulant treatment (warfarin). At operation we
      discovered a nearly complete resolution of the thrombus: only its adherent base
      was still present. Therefore we performed a routine endarterectomy and a PTFE
      patch angioplasty. The latter case reported had no preliminary medical treatment;
      a thrombus extending from carotid bulbus to external and internal carotid was
      detected and then removed without any distal embolization. Arteriotomy was closed
      by Dacron Velour patch angioplasty. No perioperative stroke occurred in both
      cases: our second patient showed a partial resolution of his motility deficit.
      According to our limited experience, delayed surgical treatment of intraluminal
      carotid thrombi seems not to be affected with higher risk of perioperative stroke
      than prophylactic carotid endarterectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254252
TI  - Percutaneous transluminal angioplasty (PTA) of supra-aortic arteries especially
      of the carotid and vertebral artery. An alternative to vascular surgery?
AB  - This paper presents personal experience of 174 percutaneous transluminal
      angioplasties (PTA) and more than 1,000 worldwide published results of
      angioplasty of supraaortic stenoses especially of the carotid and vertebral
      artery. The technique of the angioplastic procedure, essential pretherapeutic
      diagnostic methods and indications of PTA are described and discussed. Results of
      personal and published experience indicate that PTA is an effective and
      alternative method to vascular surgery in the treatment of symptomatic carotid
      artery stenoses. With strict definition of the indication, the complication rate
      for PTA is not likely to be higher than that for vascular surgical treatment. PTA
      of carotid artery stenosis should be used exclusively in medical centers in which
      a cooperation by vascular surgeons, internists, neurologists, and interventional
      neuroradiologists comes true.

PMID- 8254253
TI  - Intraoperative angioscopy after carotid endarterectomy.
AB  - The angioscopic evaluation of the carotid bifurcation has proved valuable for
      intraoperative quality control after carotid endarterectomy (CEA). From January
      1989 to July 1990, intraoperative angioscopy was performed in 196 patients
      undergoing CEA. We used a 2.2, 2.8 or 3.6 mm angioscope inserted at the end of
      the CEA through the remaining opening in the suture line. The angioscopic
      findings were classified as follows: I--no pathology (68%), II--thrombi, smaller
      debris, suture irregularities (29%), III--intima flap, endoscopic removal (3%),
      IV--intima flap, surgical redo (3%). Our results support the practicability and
      importance of intraoperative angioscopy for surgical decision making. It is
      possible to rinse out thrombi or remove remaining debris using flexible forcepy,
      under direct visual control. There were no significant complications related to
      the angioscopic procedure.

PMID- 8254254
TI  - External carotid artery repair in cerebrovascular insufficiency.
AB  - From January 1985 to October 1992 ten patients were submitted to reconstruction
      of the external carotid artery (ECA). Nine were males and one female with age
      that ranged from 64 to 74 years, mean 68. All were symptomatic due to TIAs in
      seven and amaurosis fugax in four of this group, previous completed stroke plus
      TIAs in two and chronic low perfusion in one. Associated risk factors were
      smoking (8 pts: 80%), coronary disease (5 pts: 50%), hypertension (4 pts: 40%),
      diabetes (4 pts: 40%) and peripheral arterial obstructive disease (2 pts: 20%).
      All patients were submitted to non invasive (Doppler C. W., Echo-color Doppler)
      studies as well as angiography. All the patients had an occlusion of the internal
      carotid artery (ICA) unilateral and homolateral to external carotid stenosis in 8
      and bilateral in 2; in addition three patients had a non haemodynamic stenosis of
      the contralateral ICA. One patient had an occlusion of the common carotid artery
      with collateral supply to the ECA; nine had severe stenosis of the ECA at the
      origin. In one case a homolateral vertebral stenosis was detected as well as a
      prevertebral contralateral subclavian stenosis in another one. Surgery was
      advised to correct amaurosis fugax, to increase external-internal collateral
      supply in order to avoid cerebral ischaemia and prior to contralateral ICA
      endarterectomy. All patients were operated upon under general anesthesia; an
      endarterectomy with a PTFE patch was performed in 9 cases, while in one a
      subclavian-ECA bypass was carried out using an autologous vein segment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8254255
TI  - [Fifty-three atherosclerotic carotid stenoses in an irradiated environment].
AB  - Fifty-three atheromatous carotid stenosis in a previously irradiated zone were
      operated upon between January 1983 and December 1991. A case control
      (retrospective) study confirmed the reality, even within the context of multiple
      artery atheromatous localizations, of an atypical profile suggestive of
      incrimination of the radiation: extension of the atheromatous lesions distally in
      the common carotid, proximally beyond the bulb. An isolated atheromatous lesion
      in the common carotid is very suggestive of postradiation atheroma, which also
      presents specific histologic features: peri-adventitial inflammation, adventitial
      and medial sclerosis. These changes are not accompanied by any particular
      neurologic clinical manifestations, but require frequent changes in surgical
      strategy: bypass rather than endarterectomy; the extent of the lesions decides
      whether the proximal implantation of the bypass is in the lower part of the
      common carotid or the subclavian. Radiotherapy adds to the difficulty of
      dissection and provokes a slight increase in morbidity, but the long term
      prognosis is analogous to that of usual atheromatous lesions with, however, the
      risk of atherosclerotic changes proximally.

PMID- 8254256
TI  - Computer-based patient education revisited.
AB  - Good patient education teaches ideas and skills that help patients cope with
      immediate medical problems, maintain health and avoid disease. Patient education
      is increasingly important as hospital stays are shortened, patients become more
      active health consumers, and there is more need to document informed consent for
      treatment. It is difficult to provide consistent high quality patient education
      and reimbursement is problematic. Computers have unique attributes for
      individualized, effective instruction, including variable lesson pacing
      controlled by the patient and the ability to accurately track the level of
      patient understanding to document informed consent and for third party
      reimbursement purposes. The ability of the computer to persuade as well as inform
      helps motivate behavior change. The unrealized potential of computer-based
      patient education makes clear the need for further research on how to effectively
      use this unique tool for patient education.

PMID- 8254257
TI  - Intelligent Medical Record--entry (IMR-E).
AB  - This paper describes an automated medical record designed to allow providers to
      enter patient data at the point of care. The system runs on PCs and Macintoshes
      and uses a graphical user interface and object-oriented programming to take
      advantage of current mouse and pen technologies. The provider acquires all
      relevant patient data by pointing and clicking at selections on input screens,
      many of which contain anatomical drawings to help the provider quickly and
      accurately describe patient findings. The system also generates a grammatically
      correct progress note using the problem-oriented structure. Furthermore, items
      identified in the assessment and plans portion of the program can be ported to
      expert systems for medical decisions assistance or to billing systems. The system
      allows the provider to obtain the necessary information on a focused patient
      visit in less than 5 min or to enter a complete history and physical.

PMID- 8254258
TI  - Report of colon cancer detection in mass surveys using immunological occult blood
      test (Latex method).
AB  - Occult blood test for the screening of colon cancer has been made by
      immunological method using latex agglutination for 4 years since 1988. A total of
      35,139 persons have received the screening test and out of 1886 persons, that is,
      5.4% showed positive. Five hundred seventy of the positive result subjects
      (30.2%) underwent barium enema examination. Three hundred fifty nine subjects
      (62.8%) showed some abnormal findings. They underwent colonoscopic examination
      and 45 of them (7.9%) had colon cancer. Twenty six of these were of early stage
      type and 19 persons were of advanced stage.

PMID- 8254259
TI  - Sigmoidoscopy and other tests for screening of colorectal cancer.
AB  - We have been carrying our mass detection for colorectal cancer with fecal occult
      blood test and sigmoidoscopy. The occult blood test is negative in 60% with
      colorectal cancer.

PMID- 8254260
TI  - Prognostic classification for AIDS patients in Brazil.
AB  - We studied the survival rates and the prognostic variables that corresponded to
      death during hospitalization in 312 AIDS CDC group IV patients in Sao Paulo.
      Discriminant analysis proved to be a good tool to perform the exploratory data
      analysis that guided the survival analysis groups. It selected nine variables
      that were important in the progress of the disease: age, time elapsed from the
      first manifestations of the disease, gender, infection by helminths, number of
      risk groups to which the patient belonged, number of infections by fungi, history
      of transfusion, presence of esophageal candidiasis, and infection by
      Cryptosporidium sp. Although some of these variables may be of limited importance
      in developed countries, and some variables that we expected to be important were
      not present in the final discriminant function, we believe these results may
      guide future research in prognosis of death in hospitalized AIDS patients.

PMID- 8254261
TI  - An artificial intelligence system to predict progression of immune dysfunction in
      healthy older patients.
AB  - In 1983, forty nine participants returning for their annual HEALTH WATCH
      evaluation were assessed for immune function status and served as healthy
      controls in an early study of "normal" reference values for T4 and T8 lymphocyte
      counts and T4/T8 lymphocyte ratios, B lymphocyte counts, and other laboratory
      tests for immune function then available. Balascopy, a computer-assisted pattern
      recognition system for detection, quantification and cognition of multiple
      imbalances among clinical laboratory and health behavioral parameters,
      facilitates identification of otherwise healthy individuals with evidence of
      early immune dysfunction. When the T4 and T8 immunology tests were combined with
      7 health index behavioral subscores, and 24 routine clinical laboratory tests, we
      are able to obtain a bodyprint unique for each patient, providing a comprehensive
      health status profile specific for that individual. These bodyprints serve as
      tools for the evaluation of otherwise undetectable metabolic, immunological and
      behavioral imbalances in a given patient in an unprecedented individualized
      manner. We show here a longitudinal look at a balascopic evaluation of one
      patient who has evidence of progressive immune dysfunction with development of
      only mild clinical symptoms.

PMID- 8254262
TI  - Management problems in continuous care of male patients with mild hypertension
      with special reference to alcohol-intake.
AB  - Forty two male patients with borderline and mild hypertension were followed up
      for 3.9 years without medication. During this period, all subjects had
      nonpharmacological interventions including salt restriction, weight reduction,
      anti-smoking or anti-alcohol instruction, and physical exercise after the
      established protocol. Comparisons of biomedical data between pre- and post
      observation revealed no significant improvements. Although the smoking habit
      decreased during this period, the drinking habit rarely changed and even
      significant increase of the total amount of alcohol ingestion was observed. These
      data indicate great limitation of nonpharmacological intervention in the care of
      these asymptomatic hypertensive patients for a lifelong base.

PMID- 8254263
TI  - Exploratory data analysis of hyperlipidemia on the Macintosh: software tools for
      analysis of biochemical, clinical, and genetic variables in 1677 consecutive
      lipid clinic patients.
AB  - Exploratory data analysis (EDA) software facilitates unstructured, iterative open
      exploration of complex datasets with the aid of multiple linked graphical
      displays. We are investigating relationships between plasma lipoproteins and
      coronary artery disease by retrospective analysis of 1677 consecutive UCSF Lipid
      Clinic patients. Our preliminary experience is with Data Deck 3.0 although
      several additional software programs (JMP 2.0, Systat 5.1, Minitab 8.0, StatView
      4.0) are mentioned. Lipid diagnosis (751 women and 925 men) was 22% primary
      hypercholesterolemia, 19% combined hyperlipidemia, 3% dysbetalipoproteinemia, 15%
      endogenous lipemia, 4% mixed lipemia, 5% elevated Lp(a) and 32% with no major
      lipid abnormality. We found the Macintosh platform (68030) to be flexible and
      powerful for analysis of moderate size (less than 1 Mb) clinical datasets. High
      resolution color monitors (1024 x 768 pixels), fast hard disks (< 18 msec) and
      moderate amounts of system memory (8 + Mb) facilitate exploratory analysis.

PMID- 8254264
TI  - Correlative evaluation of serum lipid, blood glucose, blood pressure, serum
      immunoreactive insulin, and liver function in persons undergoing regularly
      scheduled health evaluations.
AB  - Two hundred and thirty eight persons were examined to evaluate the interrelations
      among seven key factors for arteriosclerosis: body mass index (BMI), systolic
      blood pressure (BPs), plasma glucose (PG), serum cholesterol (CHO), serum
      triglyceride (TG), serum glutamic-pyruvic transaminase (SGPT), and serum insulin
      (IRI). BPs showed the significant positive correlation with PG (r = 0.346), BMI
      (r = 0.318), and IRI (r = 0.200). However, there were no significant correlations
      between BPs and CHO, between BPs and TG, between BPs and SGPT. SGPT showed the
      significant positive correlation with IRI (r = 0.367), BMI (r = 0.268), and TG (r
      = 0.343); but no significant correlations were observed in relations between SGPT
      and PG, between SGPT and BPs, between SGPT and CHO. IRI showed the significant
      positive correlations with TG (r = 0.234), and PG (r = 0.427). These data suggest
      that IRI has an effect on BPs and SGPT. The effect of IRI on BPs relates with PG
      but does not relate with serum lipid. The effect of IRI on SGPT relates with TG
      but not with PG.

PMID- 8254265
TI  - Influence of meals and night shifts on health.
AB  - (1) The effect of twice-daily meals on a body weight (BW) and blood pressure
      (BP), (2) the effect of working night shifts on BPs, and (3) a relationship
      between a meat diet and cedar pollinosis were statistically investigated with
      working men who had an annual medical examination. As a result, the effect of
      twice-daily meals on BW and BP was not different from thrice-daily meals on BW
      and BP. However, cases of twice-daily meals had larger percentages of alcohol
      drinkers and cigarette smokers. The night shift workers had almost the same
      frequency of hypertension as compared with day duty workers. A daily diet of meat
      including beef, chicken, and pork had a close relationship with cedar pollinosis.

PMID- 8254266
TI  - Seasonal variation in serum cholesterol levels in health screening populations
      from the U.K. and Japan.
AB  - We have performed time series analyses on data from 140,000 men and 32,000 women
      in the U.K. and 30,000 men and 12,000 women in Japan, seen over periods ranging
      from 4 to 6 1/2 years, in order to test for seasonal variation in serum
      cholesterol levels. In both countries and both sexes we found a strong seasonal
      effect, with mean cholesterol levels being some three to five percent higher in
      winter than in summer. Mean monthly cholesterol levels were negatively correlated
      with mean monthly air temperatures (r = -0.60 to -0.71). The seasonal differences
      observed were independent of changes in body weight, and have important
      implications both for long-term epidemiological or follow-up studies, and for the
      interpretation of patient data.

PMID- 8254267
TI  - Recommendation for an exercise prescription to prevent coronary heart disease.
AB  - Healthy male and female adults who visited the Japanese Red Cross Health Care
      Center were undertaken to the study of hematological examination, blood
      chemistry, electrocardiography and exercise loading test by bicycle ergometer. We
      attempted to evaluate the medical check up system for decision making of exercise
      prescription and useful exercise test to prevent coronary heart disease (CHD).

PMID- 8254268
TI  - Usefulness of anaerobic threshold for evaluating daily life activity and
      prescribing exercise to the healthy subjects and patients.
AB  - Forty-three subjects were studied as for the relationship between anaerobic
      threshold (AT) and medical data including individual life style. Age, habit of
      exercise, and obesity are related to AT, showing a correlation coefficient of
      0.533, 0.457 and 0.428, respectively. On the other hand, plasma lipid levels and
      alcohol are not so strongly related to AT, showing low correlation coefficient of
      0.241 and 0.209 respectively. No correlation is found on the other factors such
      as FBS, Liver and blood pressure etc. Physical active life, commuting time,
      cumulative exercise hours in a month and work hours in a month are correlated to
      AT, showing correlation coefficient of 0.799, 0.734, 0.708 and 0.671,
      respectively, and even "more than once a month" frequency of exercise has
      affected AT. In conclusion, AT is a useful index for evaluating daily life
      activity and prescribing exercise regimen.

PMID- 8254269
TI  - The effect of obesity on ventilatory response and anaerobic threshold during
      exercise.
AB  - To facilitate making the physical fitness programs for obesity control, we
      investigated the effects of obesity on the ventilatory response during exercise
      and exercise tolerance. One hundred eighteen adults were divided into a normal
      group and fatty group by percentage of body fat. Each subject performed a
      submaximal exercise test under the gas-exchange measurement. The fatty group was
      inferior to the normal group in exercise tolerance. The respiratory mode, during
      exercise, in the fatty group was characterized by higher respiratory rate and
      less tidal volume compared with the normal group. This mode may result in
      increased dead space and therefore unavailable ventilation capacity. These data
      suggest that the characteristic respiratory mode in the fatty group was a factor
      in the lower exercise tolerance.

PMID- 8254270
TI  - Serum urate as a free radical scavenger in diabetics.
AB  - We have looked at the relationship between serum urate and the molar equivalent
      serum antioxidant capacity (MESA) in diabetic and normal individuals who attended
      St Bartholomew's Hospital diabetic clinic and BUPA Health Screening Centre,
      London, and have compared serum antioxidant capacity between the two groups.
      Sample response curves showed less serum antioxidant potential in diabetics than
      in nondiabetics, and a linear relationship between serum urate and MESA. Simple
      regression analysis gave a correlation coefficient of 0.9 (p < 0.0001).
      Significant differences between the two groups were found for both mean MESA
      values (p < 0.0001) and mean uric acid levels (p < 0.005).

PMID- 8254271
TI  - Insecurity of the ECG interpretation data as a health mass screening--the serial
      reliability evaluation study.
AB  - To evaluate the reliability of the interpretations of ECG data which have been
      stored yearly as health mass screening data between 1982 and 1991 in an industry,
      we recently analyzed the data variation of 10,546 samples. So as not to ignore
      the longitudinal health management, we are going to reevaluate the clinical
      significance of the ECG interpretation data, which were stored as an item of
      health mass screening.

PMID- 8254272
TI  - Electrocardiographic surveys with respect to high voltage of the left ventricle.
AB  - A total of 1012 persons were divided into the following four groups according to
      the values of both SV1 + RV5 by the criterion of Sokolow and Lyon and cardio
      thoracic ratio (CTR). In all cases the blood pressure, chest X-ray, body surface
      area, degree of obesity, and chest PA length were measured. From the above data,
      it was concluded that cases in GII had fat physiques and those in GIII were
      slender. It is widely known that there are many factors which produce a high
      voltage in the left ventricle on ECG. This study suggests that the physique is
      one of many important factors which cause a high voltage in the left ventricule
      on ECG.

PMID- 8254273
TI  - Evaluation of impairment related to low back pain.
AB  - Low back pain is the leading cause of disability and expense from work-related
      conditions in the United States. Forty percent of the expense of the worker's
      compensation program is spent on claims involving the low back. There are several
      systems of impairment evaluation in use in the United States, but the most
      commonly used has been developed by the American Medical Association. Evaluation
      of impairment related to the low back is expressed as a percent impairment of the
      whole person and is calculated by combining values related to: (1) diagnostic
      based categories, (2) range of motion of the spine, and (3) neurologic deficits
      in the lower extremities. Using this system, and given a cooperative patient, a
      reproducible quantification of impairment can be obtained to help administrators
      of the worker's compensation system more fairly compensate injured workers for
      partial permanent disability.

PMID- 8254274
TI  - A study on the development of a filing system for funduscopic images with a
      personal computer for Twin AMHTS.
AB  - A filing system for ocular funduscopic image data was developed by using a
      personal computer for the Twin AMHTS. The development of the system was tried as
      one of the data transfer system including image data between two similar AMHTSs
      named the Twin AMHTS through the information network system. The filing system is
      capable of storing 26782 data of ophthalmoscopic pictures with a data compression
      mode by using a magneto-optical disk (MOD) whose storage capacity of both sides
      is 616 MB. It takes no long time for retrieval and display of the image data in
      the filing system. Good quality of compression and decompression obtained and
      reproducibility of the ocular fundus picture is favorable regardless of normal or
      abnormal cases. As a result, it is suggested that the developed system has
      practical utility although it requires more improvement.

PMID- 8254275
TI  - Health program for VIP's.
AB  - The question about special health program for VIP's has been discussed several
      times. A definition of VIP is a key person either in top management or a person
      with unique competence in an organization. In small companies you find 5-10
      VIP's, in bigger companies up to 50. Our customers indicated a positive interest
      in a new type of program. They were not satisfied with just a standard screening.
      They wanted more from screening than just dealing with symptoms of not wellbeing.
      Most of them had earlier joined different personal development programs. They
      find those programs useful with well-motivated reasons for change in life
      patterns. Therefore as a top management consultant, but also certified to work
      with lifestyle, stress and axiological profile, I was at that time training top
      management both as individuals and as a team. It was therefore easy for me to
      combine a personal development program with lifestyle-health screening. In our
      new program for VIP's we therefore work with both individuals and teams and with
      both health and personal development.

PMID- 8254276
TI  - George Zur Williams.

PMID- 8254277
TI  - Hard drinking water and ischemic heart disease: calcium, bloodlipids, and acute
      myocardial infarcts.

PMID- 8254278
TI  - The case for restructuring health care in the United States: the Hawaii paradigm.
AB  - Health care in the United States is plagued by many problems. This includes
      excessive specialization with too few generalists, burdensome bureaucratic
      federal rules and regulations, and outlandish malpractice awards--all
      contributing to costs of care that exceeds all other nations. Cost has
      erroneously been identified as the cause of the problem rather than being one of
      many results of a failing system. Rather than repetitive unsuccessful efforts to
      tinker with cost as the cause, it makes far more sense to design and build a
      better structure of health care including expanding the existing biomedical model
      into a broader biomedical-psychosocial model. Hawaii, with virtually 100% of its
      population insured, is closer to this model than most states. It also manages to
      be ranked the healthiest state with one of the lowest health care costs in the
      nation.

PMID- 8254279
TI  - The occurrence of mitochondrial variations including large mitochondria in
      osteoclasts following calcitonin treatment.
AB  - Calcitonin-treated osteoclasts with mitochondrial variations, including large
      mitochondria, and osteoclasts not treated with calcitonin (control osteoclasts)
      were examined using cytochrome c oxidase activity and morphological analysis of
      mitochondria. The calcitonin-treated osteoclasts were divided into two types. One
      was osteoclasts with only a clear zone, which contained many type 1 mitochondria
      with the reaction products of cytochrome c oxidase in both the inner membrane of
      the cristae and the outer compartment in the vascular side and a comparatively
      small number of type 1 mitochondria in the resorptive side. The other type was
      osteoclasts with a mature ruffled border, in which many type 1 mitochondria were
      observed in both sides. Most of the large mitochondria were type 1, and these
      were observed only in the vascular side of the osteoclasts with only a clear
      zone, and in both sides of the osteoclasts with a mature ruffled border. In
      statistical analysis, the cross-sectional area of mitochondria in the vascular
      side of calcitonin-treated osteoclasts was larger than that of those in the
      resorptive side, and the numerical percentage of type 1 mitochondria in the
      vascular side was greater than that in the resorptive side. In contrast, the
      cross-sectional area of mitochondria in the vascular side of control osteoclasts
      was smaller than that in the resorptive side, and there was no significant
      difference between the two groups in the numerical percentage of type 1
      mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254280
TI  - Detection of endogenous avidin-binding proteins in rat liver cells by transblot
      and electron microscopy.
AB  - Peroxidase-conjugated avidin was used to detect the endogenous avidin-binding
      proteins in rat tissues. By a transblot method, avidin-peroxidase interacted with
      proteins of mitochondrial fractions of rat liver with estimated molecular weights
      of 120,000 and 74,000. The proteins were identified as pyruvate carboxylase (120
      kDa, pI 6.4) and methylcrotonyl-CoA carboxylase (74 kDa, pI 7.2) by two
      dimensional gel electrophoresis and transblot method. The estimated molecular
      weight of an additional band (220,000) detected in the cytosolic fraction of rat
      liver was consistent with acetyl-CoA carboxylase. Intense staining also occurred
      with kidney, heart, ovary and adipose tissue, moderate with large and small
      intestine, cerebrum and cerebellum, and very faint with testis, lung and spleen.
      The sections of rat liver embedded in LR white were incubated with avidin
      colloidal gold conjugate and examined under an electron microscope. The
      glutaraldehyde-perfused rat liver blocks were also incubated with streptavidin
      ferritin conjugate and the ultrathin sections were cut and examined. The majority
      of gold and ferritin particles were found in the mitochondria of liver cells. No
      other cellular compartment was labeled except the cytosol which accounted for
      approximately 20% of the total labeling of the hepatocytes. The present procedure
      is a simple, rapid and inexpensive method for detecting the intracellular
      localization of endogenous avidin-binding proteins in the cells.

PMID- 8254281
TI  - Persistent adrenergic reinnervation of previously denervated muscle in cat.
AB  - Synapse formation by aberrant nerves at chronically denervated intrinsic
      laryngeal muscles was observed even at 21 months after the transection of the
      recurrent laryngeal nerve in cats. Some of the aberrant nerves were adrenergic,
      and these nerve terminals were in synaptic contact with the postsynaptic membrane
      of the neuromuscular junctions together with non-adrenergic nerve terminals.
      Therefore, heterogeneous reinnervation between adrenergic nerve and muscle was
      found to be maintained for a long time.

PMID- 8254282
TI  - Hormone and growth factor subunits: a novel perception of cell growth regulation.

PMID- 8254283
TI  - Biochemical and immunological characterization of oestrogen receptor in the
      cytosolic fraction of gluteal, omental and perirenal adipose tissues from sheep.
AB  - Determination of the presence and characterization of oestrogen receptors (ERs)
      in subcutaneous and internal fat depots were performed and compared with ERs in
      the uterus using ligand binding and immunological techniques. Successful and
      consistent measurement of ERs in ovine adipose tissue could only be accomplished
      in animals depleted of endogenous sex steroids by combined ovariectomy and
      adrenalectomy. Scatchard, sucrose gradient and Western blot analyses all
      confirmed the presence of ERs in the cytosolic fractions of various adipose and
      uterine tissues from ovariectomized-adrenalectomized ewes. The approximate Kd
      values of 0.1-0.4 nmol/l for oestradiol binding in cytosolic fractions of
      gluteal, omental and perirenal adipose tissues were similar to the expected high
      affinity binding of Kd 0.35 nmol/l observed in uterine tissue. The binding was
      specific for oestrogens, as unlabelled diethylstilboestrol and oestradiol
      effectively competed with labelled hormone for receptor sites and progesterone,
      R5020, testosterone and dexamethasone all failed to compete. Mean (+/- S.E.M.)
      concentrations of ERs, expressed as fmol specific binding sites per mg protein,
      were much lower (P < 0.05) in adipose tissues than in uterine tissue (975 +/-
      33). However, the content of ERs was greater (P < 0.05) in subcutaneous gluteal
      fat (11.5 +/- 0.8) than in the internal omental or perirenal fat (5 +/- 0.6)
      depots. ERs from adipose and uterine tissues both migrated as moieties of 8S on 5
      20% sucrose gradients. Western blot analysis of ERs from uterine and adipose
      tissues in the presence of protease inhibitors demonstrated an immunostaining
      band with a molecular mass of 67 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254284
TI  - Interactions between growth hormone and nutrition in hypophysectomized rats: body
      composition and production of insulin-like growth factor-I.
AB  - Hypophysectomy of adult rats results in a loss of body growth which can be
      reversed by treatment with GH. The increased growth caused by administration of
      GH is accompanied by an increase in food consumption. The effects of GH and
      interactions with nutrition were investigated by treating hypophysectomized rats
      with GH and either providing unrestricted food or preventing the increased food
      consumption by pair-feeding with the same intake as that of the hypophysectomized
      animals. Over the 7-day experimental period, the GH-treated animals grew
      significantly when food was available ad libitum but did not gain body weight
      when an increase in food intake was prevented. However, there was a significant
      interaction between GH and nutrition on body composition; GH significantly
      decreased body fat and increased the protein: fat ratio only in the animals with
      the restricted intake. Gastrocnemius muscle weight was increased by GH regardless
      of food intake, but heart weight did not increase and liver weight was actually
      decreased by GH treatment when food intake was restricted. Serum concentrations
      of insulin and insulin-like growth factor-I (IGF-I) were increased by GH in the
      rats with food available ad libitum but not in the pair-fed rats. However, the
      liver concentration of IGF-I and its mRNA were increased by GH although the
      increase in IGF-I mRNA was modulated by the restricted food intake. The decreased
      weight of the liver in the pair-fed GH-treated rats, despite the increase in IGF
      I mRNA, suggests that IGF-I does not influence liver growth. In the gastrocnemius
      muscle, however, GH increased IGF-I mRNA concentration similarly in both rats
      with food available ad libitum and in pair-fed rats. Decreased nutrition
      therefore modulated the action of GH but emphasized its nutrient partitioning
      effect, thus increasing the anabolic drive towards skeletal muscle growth; this
      appeared to be mediated by the local production of IGF-I within the muscle.

PMID- 8254285
TI  - Suppressed expression of the cytochrome P45017 alpha protein in the testicular
      feminized (Tfm) mouse testes.
AB  - The testes of testicular feminized (Tfm) mice synthesize and secrete abnormally
      low amounts of testosterone, as a consequence of selectively decreased cytochrome
      P450(17 alpha) activity. To investigate the mechanism of this deficiency, three
      steroidogenic enzymes were immunolabeled in the testes of normal and Tfm adult
      (2.5-6 month old) mice. Cholesterol side-chain cleavage cytochrome P450 (P450scc)
      and delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) were detected in the
      Leydig cells of both normal and Tfm mice whereas, in contrast to normal mice,
      only a small proportion of Leydig cells were immunostained for cytochrome P450-17
      alpha-hydroxylase, C17-->20 lyase (P450(17 alpha)) in the testes of Tfm mice. The
      numbers of cells differed from male to male and interestingly were markedly
      higher in the right testis. Explants of testes from Tfm mice were kept in organ
      culture at 32 degrees C for 45 h, with or without dibutyryl cyclic AMP (100 or
      500 mumol/l). All Leydig cells remained positive for P450scc and 3 beta-HSD, and
      P450(17 alpha) became detectable in the majority of Leydig cells in both left and
      right testes, showing that the lack of expression of P450(17 alpha) protein in
      Tfm mouse testes in vivo is not structural but is a regulatory phenomenon.

PMID- 8254286
TI  - Investigation of mechanisms mediating the increase in plasma concentrations of
      thyroid hormones after a meal in young growing pigs.
AB  - These studies investigated a number of possible mechanisms which could mediate
      the increase in plasma concentrations of thyroid hormones after a meal in young
      growing pigs. It has been established that in animals fed one meal a day, an
      immediate rise in plasma 3,5,3'-tri-iodothyronine (T3) and a slightly delayed
      increase in thyroxine (T4) levels are followed by a more sustained peak in both
      hormones several hours later. The increase in thyroid hormones involves both
      total and free T3 and T4, and there is no change in plasma albumin, the high
      capacity thyroid hormone-binding protein in the pig. It has also been shown that
      the immediate rise in plasma T3 is not mediated either by an increase in plasma
      glucose concentration or by neural mechanisms associated with distension of the
      gastrointestinal tract. However, the finding that plasma T3 increases rapidly
      after feeding in thyroidectomized animals maintained on a replacement dose of T4
      alone, indicates the source of T3 to be non-thyroidal. It is concluded that the
      rise in plasma thyroid hormones after a meal depends on the energy content of the
      food but not directly on the circulating glucose levels. The immediate increases
      in plasma T3 and T4 are probably due largely to a redistribution of the hormonal
      pools, and peripheral 5'-monodeiodination of T4 may also contribute significantly
      to the post-prandial rise in T3. The potential significance of these findings in
      relation to both the metabolic and growth-promoting effects of thyroid hormones
      is discussed.

PMID- 8254287
TI  - Ovarian and hepatic insulin-like growth factor-I gene expression and associated
      metabolic responses in prepubertal gilts subjected to feed restriction and
      refeeding.
AB  - The effects of feed restriction and refeeding on ovarian and hepatic insulin-like
      growth factor-I (IGF-I) gene expression, systemic and ovarian IGF-I
      concentrations and on associated metabolic changes were measured in prepubertal
      gilts. Eleven pairs of littermate gilts (70.7 +/- 4.7 kg) were placed on a
      maintenance level of feeding for 7 days (days 1-7). On day 8, littermates were
      either fed at a maintenance level of energy or fed to appetite for a further 6
      days. Blood samples were taken on day 13 (07.00-16.00 h) to determine plasma
      insulin and IGF-I, and on day 14 (02.00-06.00 h) to determine plasma GH levels.
      Following slaughter on day 14, one ovary from each animal was retained to measure
      follicular fluid IGF-I and oestradiol concentrations. The remaining ovary and a
      sample of liver were retained for IGF-I mRNA analysis using a ribonuclease
      protection assay. Six days of refeeding significantly increased plasma IGF-I (P <
      0.005) and basal insulin (P < 0.05) but there was no effect on plasma GH. Ovarian
      follicular volume and diameter were significantly larger after refeeding (P <
      0.05), with no effect on follicular fluid oestradiol concentrations. Mean
      follicular fluid IGF-I concentrations were unaffected by treatment. However, the
      relationships between individual follicular IGF-I concentrations, absolute
      follicular fluid IGF-I contents and follicle volume were affected by feeding
      level (P < 0.05). Regression analysis of the same data also revealed that at this
      stage of maturity, small follicles had greater follicular fluid concentrations of
      IGF-I than larger follicles. Refeeding increased the amount of IGF-I mRNA in
      hepatic but not ovarian tissue. We conclude that there is differential regulation
      of the IGF-I gene in porcine hepatic and ovarian tissues, and that ovarian
      factors other than, or as well as, IGF-I are involved in the regulation of
      ovarian responses to refeeding.

PMID- 8254288
TI  - The relationship between the physicochemical properties and the biological
      effects of alloxan and several N-alkyl substituted alloxan derivatives.
AB  - Alloxan causes diabetes in experimental animals through its ability to destroy
      the insulin-secreting B-cells of the pancreas. Alloxan is hydrophilic and
      chemically unstable; it is reactive toward thiols, undergoing redox cycling in
      the presence of glutathione and oxidizing protein-bound thiol groups, as
      reflected by inhibition of the thiol enzymes, hexokinase and glucokinase. It is
      apparently also selectively taken up by the GLUT-2 glucose transporter in the
      pancreatic B-cell membrane. In order to investigate which, if any, of these
      physicochemical properties are important in the toxic action of alloxan, we have
      examined seven N-alkyl substituted alloxan derivatives of various diabetogenic
      activity. Hydrophilicity was identified as a factor essential for
      diabetogenicity. Stability, rate of redox cycling and reactivity toward thiol
      groups were not correlated with diabetogenicity. Selective uptake by the GLUT-2
      glucose transporter is not a prerequisite for the diabetogenicity of alloxan
      derivatives.

PMID- 8254289
TI  - Effects of fasting, elevated plasma glucose and plasma insulin concentrations on
      milk secretion in women.
AB  - In order to determine whether short term variations in plasma glucose and/or
      insulin influence milk lactose secretion in women, the effects of fasting and
      increased blood insulin and glucose on milk volume and composition were studied
      with glucose clamp methodology in exclusively and partially breast-feeding women.
      Twenty hours of fasting had no discernable effect on the output of milk or its
      macronutrient composition. Four hours of increased plasma insulin, studied under
      conditions where plasma glucose was maintained at the fasting level, had no
      effect on milk volume, milk glucose concentration, total fat content or lactose
      secretion rate. Increased plasma glucose, maintained at twice fasting levels for
      4 to 6 h, produced a threefold increase in milk glucose concentration but had no
      significant effect on the rate of lactose synthesis. In partially breast-feeding
      women producing no more than 200 ml milk per day, a similar degree of
      hyperglycaemia increased milk glucose more than fourfold but did not
      significantly increase the milk secretion rate. It is concluded that human milk
      production is isolated from the homeostatic mechanisms that regulate glucose
      metabolism in the rest of the body, in part because the lactose synthetase system
      has a Km for glucose lower than the concentration available in the Golgi
      compartment.

PMID- 8254290
TI  - Effect of exogenous bovine growth hormone and ovariectomy on prepubertal mammary
      growth, serum hormones and acute in-vitro proliferative response of mammary
      explants from Holstein heifers.
AB  - Sixteen prepubertal Holstein Friesian heifers were used to study the effect of
      long-term administration of bovine GH (bGH) on mammary development in intact and
      ovariectomized heifers. Eight heifers were ovariectomized at 2.5 months of age.
      Four intact and four ovariectomized heifers received subcutaneous injection of
      bGH (15 mg/day) for 15 weeks starting at 176 +/- 3 days of age (147 +/- 3 kg body
      weight), while the remaining eight heifers received an equal volume of excipient.
      Blood samples were collected weekly from 2 months of age. Heifers were
      slaughtered on the day after the last injection of bGH or excipient. Mammary
      gland development was quantified by dissection, chemical analysis and computer
      tomographic scanning. Mammary growth response at the time of slaughter was
      examined in cultures with explants prepared from parenchyma. Histological and
      histoautoradiographic studies with explants were performed. Treatment with bGH
      resulted in a significantly (P < 0.05) smaller mammary gland because of a reduced
      amount of extraparenchymal tissue. Ovariectomy markedly reduced the amount of
      parenchymal tissue. Growth response in mammary explants showed no treatment
      differences, suggesting that the decreased amount of parenchyma in ovariectomized
      heifers was caused by a decrease in mammary cell proliferation occurring some
      time prior to slaughter. The histological composition of mammary parenchyma was
      not changed by bGH treatment. However, ovariectomy resulted in less epithelial
      tissue (P < 0.001) and lumen (P < 0.05) and more stroma (P < 0.001), expressed as
      percentage tissue area. Serum hormone concentrations of bGH and insulin-like
      growth factor-I (IGF-I) were increased by bGH treatment in both intact and
      ovariectomized heifers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254291
TI  - Regulation of 11 beta-hydroxysteroid dehydrogenase by sex steroids in vivo:
      further evidence for the existence of a second dehydrogenase in rat kidney.
AB  - 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) catalyses the reversible
      conversion of corticosterone to inactive 11-dehydrocorticosterone, thus
      regulating glucocorticoid access to mineralocorticoid and perhaps glucocorticoid
      receptors in vivo. 11 beta-OHSD has been purified from rat liver and an encoding
      cDNA isolated from a liver library. However, several lines of indirect evidence
      suggest the existence of at least two isoforms of 11 beta-OHSD, one found
      predominantly in glucocorticoid receptor-rich tissues and the other restricted to
      aldosterone-selective mineralocorticoid target tissues and placenta. Here we have
      examined the effects of chronic (10 day) manipulations of sex-steroid levels on
      11 beta-OHSD enzyme activity and mRNA expression in liver, kidney and hippocampus
      and present further evidence for the existence of a second 11 beta-OHSD isoform
      in kidney. Gonadectomized male and female rats were given testosterone,
      oestradiol or blank silicone elastomer capsules, controls were sham-operated. In
      male liver, gonadectomy+oestradiol treatment led to a dramatic decrease in both
      11 beta-OHSD activity (69 +/- 8% decrease) and mRNA expression (97 +/- 1%
      decrease). Gonadectomy and testosterone replacement had no effect on male liver
      11 beta-OHSD. However, in female liver, where 11 beta-OHSD activity is
      approximately 50% of that in male liver, gonadectomy resulted in a marked
      increase in 11 beta-OHSD activity (120 +/- 37% rise), which was reversed by
      oestradiol replacement but not testosterone treatment. In male kidney,
      gonadectomy+oestradiol treatment resulted in a marked increase in 11 beta-OHSD
      activity (103 +/- 4% rise). By contrast, 11 beta-OHSD mRNA expression was almost
      completely repressed (99 +/- 0.1% decrease) by oestradiol treatment.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8254292
TI  - Ruminants express a prolactin receptor of M(r) 33,000-36,000 in the mammary gland
      throughout pregnancy and lactation.
AB  - Developmental variation in the expression of the prolactin receptor in the
      ruminant mammary gland was investigated. Affinity chromatography revealed that
      bovine prolactin and human GH each bound to the same mammary gland proteins,
      yielding fractions enriched in binding activity and a protein of M(r) 36,000,
      assumed to be a bovine prolactin receptor. Affinity cross-linking of 125I
      labelled human GH to mammary microsomes confirmed that the M(r) 36,000 protein
      was a bovine prolactin receptor. Binding assays of receptors in microsomes from
      the mammary tissue of cows and ewes at various stages of the
      lactational/reproductive cycle indicated developmental regulation of receptor
      concentration, but not receptor type, as no other bovine prolactin receptor type
      was detected by affinity cross-linking. These results suggest that differences in
      the response to prolactin in the mammary gland at various developmental stages in
      ruminants are not due to the expression of different forms of the prolactin
      receptor, and the lack of a prolactin effect on established lactation in
      ruminants is not due to the absence of the M(r) 36,000 form of the prolactin
      receptor.

PMID- 8254293
TI  - Thyroidectomy progressively renders the reproductive system of starlings (Sturnus
      vulgaris) unresponsive to changes in daylength.
AB  - If starlings (Sturnus vulgaris) are transferred to long days soon after being
      thyroidectomized, they show gonadal maturation but no subsequent
      photorefractoriness, suggesting a specific role for thyroid hormones in the
      development of photorefractoriness. This study tests an alternative hypothesis:
      that following thyroidectomy all gonadal responses to photoperiodic changes are
      progressively inhibited. Photoperiodic responses of starlings were examined at
      two different times after thyroidectomy. Transfer of thyroidectomized birds to
      long days 4 weeks after thyroidectomy caused testicular growth but at a slower
      rate than in intact birds, whereas, in thyroidectomized birds kept on short days,
      testicular growth was greater than in corresponding intact birds. Thirteen weeks
      after thyroidectomy, there was little or no response to an increase or a decrease
      in daylength in thyroidectomized birds, whereas intact birds showed marked
      testicular growth or regression respectively. The results support the hypothesis
      that the reproductive system gradually becomes unresponsive to changes in
      daylength during the weeks following thyroidectomy. This long-term effect may
      mean that earlier conclusions regarding the effects of thyroidectomy need to be
      reassessed.

PMID- 8254294
TI  - Androgen regulation of circulating insulin-like growth factor-I during puberty in
      male hypogonadal mice.
AB  - This study aimed at determining the relationship of sex steroids, particularly in
      the perinatal period, to the pubertal insulin-like growth factor-I (IGF-I) surge
      in male mice. We used hypogonadal (hpg) mice, which have a major deletion in the
      gonadotrophin-releasing hormone (GnRH) gene, in order to have a model lacking all
      GnRH-induced gonadotrophin and sex steroid secretion throughout pre- and
      postnatal life. Cross-sectional data on body weights and weights of testes,
      seminal vesicles, kidneys, liver and spleen from 9 to 77 days of age were
      obtained in male hpg, heterozygous (Hz) and homozygous normal (N/N) littermates
      (n = 75-78/group). These data did not reveal any difference between Hz and N/N
      mice. Hpg mice had decreased body weights which by 70-77 days of age were
      approximately 18% less than normal controls. Testes and seminal vesicles of hpg
      mice did not demonstrate any significant postnatal growth. Relative to body
      weight, kidney weights were also markedly reduced in hpg mice (P < 0.0001),
      deviating significantly from normal by 28-35 days of age, reflecting the impact
      of androgen deficiency on a non-reproductive organ. From the cross-sectional data
      it was concluded that puberty commenced soon after weaning (21 days) in the male
      and that maturity was achieved within 4-5 weeks. Longitudinal study showed that,
      compared with normal controls, untreated hpg mice had an exaggerated pubertal IGF
      I surge (P < 0.005) which peaked in mid-puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254295
TI  - Effects of recombinant bovine somatotrophin, insulin-like growth factor-I and
      insulin on the proliferation of bovine granulosa cells in vitro.
AB  - Treatment of heifers with recombinant bovine somatotrophin (BST) significantly
      increases the population of small ovarian follicles and peripheral concentrations
      of somatotrophin, insulin-like growth factor-I (IGF-I) and insulin. To
      investigate the possible mechanism(s) involved in the action of BST on ovarian
      follicles, the effects of BST, IGF-I and insulin, given alone or in combination
      with either FSH or LH, on the proliferation of bovine granulosa cells in vitro
      were examined using a serum-free culture system. Bovine granulosa cells were
      obtained from antral follicles classified into three size categories according to
      diameter: small < 5 mm; medium-sized 5-10 mm and large > 10 mm. The proliferation
      of granulosa cells was assessed by the incorporation of [3H]thymidine into the
      cultured cells. Both FSH and LH (1-1000 ng/ml) inhibited the proliferation of
      bovine granulosa cells obtained from all three size classes of follicles in a
      dose-dependent manner. BST, at doses ranging from 1 to 1000 ng/ml, had no effect
      on the proliferation of granulosa cells from small and medium-sized follicles,
      but inhibited the division of granulosa cells from large follicles in a dose
      dependent manner. Treatment with either IGF-I (10-3000 ng/ml) or insulin (0.5
      1000 ng/ml) stimulated, in a dose-dependent manner, the proliferation of
      granulosa cells obtained from all three size categories of follicles. No
      synergistic interaction between BST (30 ng/ml) and either FSH (50 ng/ml) or LH (5
      ng/ml) was observed in granulosa cells from all three size classes of
      follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254296
TI  - The effect of acute pharmacological manipulation of central serotonin
      neurotransmission on osmoregulated secretion of arginine vasopressin in the rat.
AB  - To explore the hypothesis that serotonin (5-HT) is important in osmoregulated
      arginine vasopressin (AVP) secretion, we administered (i.p.) fluoxetine (FL) a 5
      HT reuptake inhibitor (10 mg/kg body weight), ritanserin (RIT), an antagonist at
      the 5-HT2 and 5-HT1c receptor subtypes (1 mg/kg body weight), 1-(4-iodo-2,5
      dimethoxyphenyl)-2-aminopropane hydrochloride (DOI), a 5-HT2 receptor agonist (1
      mg/kg body weight) or vehicle to rats 30 min before they were given an osmotic
      challenge. Rats received distilled water, normotonic saline (150 mmol NaCl/l) or
      hypertonic saline (500 mmol NaCl/l) (20 mg/kg i.p.) and were killed 30 min later.
      The osmotic stimulus alone produced significant (P < 0.001) effects on plasma
      osmolality and plasma sodium but FL, RIT and DOI did not have any significant
      effect on this stimulus. FL had no significant effect on the osmotic threshold of
      AVP release but significantly (P < 0.001) increased basal AVP secretion from 1.6
      +/- 1.0 to 3.1 +/- 1.3 (S.E.M.) pmol AVP/l and significantly (P < 0.001)
      increased the AVP response to changes in plasma osmolality: vehicle-treated, 0.7
      +/- 0.4; FL-treated, 1.7 +/- 0.2 pmol AVP/l per mOsm per kg. Neither RIT nor DOI
      had any significant effect on basal or stimulated AVP secretion. In a second
      study, RIT was administered 60 min i.p. prior to FL i.p. (doses as above), which
      was followed 30 min later by a hypertonic stimulus i.p. and rats were killed 30
      min after hypertonic saline treatment. RIT had no significant effect on the AVP
      response to plasma osmolality and did not significantly alter the FL-augmented
      AVP response, suggesting that neither the 5-HT2 nor the 5-HT1c receptors are
      involved in the response of AVP to FL. We conclude that FL modulates
      osmoregulated AVP secretion but that the mechanism of this is unknown and is
      apparently not through the 5-HT2 or 5-HT1c receptor subtypes.

PMID- 8254297
TI  - Regulation of serum insulin-like growth factor-I (IGF-I), hepatic growth hormone
      binding and IGF-I gene expression in the rat during pregnancy and lactation.
AB  - An apparent GH resistance occurs in pregnancy, since GH concentrations in serum
      are reported to be normal or elevated, whereas serum IGF-I falls to very low
      levels. To determine whether this GH resistance is manifest at the level of the
      hepatic GH receptor or in the ability of GH to initiate IGF-I gene expression, we
      have determined hepatic IGF-I mRNA expression, circulating IGF-I and hepatic GH
      binding during various stages of pregnancy and lactation in the rat. The
      concentration of IGF-I in serum fell from 37 +/- 5 nmol/l (means +/- S.E.M.) in
      virgin rats to 17 +/- 1 nmol/l in rats in late pregnancy, recovered in early
      lactation (31 +/- 3 nmol/l) but was again significantly lower than in virgin
      animals by mid-lactation (22 +/- 3 nmol/l). Hepatic GH binding did not vary
      significantly during pregnancy but showed a small significant decrease in early
      lactation when expressed per mg membrane protein. When expressed as GH binding
      per liver, however, there were no significant changes in GH binding at any stage.
      Liver weight increased significantly between virgin and early pregnant animals
      (7.1 +/- 0.2 g compared with 9.2 +/- 0.5 g respectively, P < 0.01) and continued
      to increase up to late lactation (14.3 +/- 0.4 g).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8254298
TI  - Thyroid hormones and bone.

PMID- 8254299
TI  - Isolation and characterization of a cytostatic histone H2B-like protein from
      fetal lungs of non-diabetic and diabetic rats.
AB  - It was observed in the course of other studies that rat fetal lung extracts
      inhibited proliferation of fetal lung cells in culture. The purpose of the
      present study was to isolate and characterize this cytostatic factor. It was
      found that fetal lungs contained a 16 kDa cytostatic factor and its concentration
      was twofold greater in fetal lungs of diabetic rats compared with control rats.
      This fetal lung cytostatic protein (FLCP) was purified by reversed-phase, heparin
      affinity and gel filtration high-performance liquid chromatography and SDS-PAGE.
      The purified protein was electroblotted onto polyvinylidene difluoride membrane
      and subjected to sequence analysis. The amino-terminal sequence of this fetal
      lung cytostatic protein was P E P A K S A P A P X K G I G K Q X X K A X X K A ...
      and showed significant homology with histone H2B; however, the amino acid
      composition of FLCP suggested that it may be structurally distinct from histone
      H2B. Ion-spray mass spectrometry suggested that FLCP was made up of at least two
      species of the protein with molecular weights of 13,776.1 and 14,007.3 and was
      different from the molecular weight of rat histone H2B predicted by its cDNA
      sequence. The concentration of FLCP, based on amino acid compositions, was 0.32
      nmol/g and 0.83 nmol/g wet fetal lung from non-diabetic and diabetic rats
      respectively. These findings suggest that the fetal rat lung produces a
      regulatory factor bearing considerable homology with but possibly different from
      histone H2B and that fetal lung immaturity during diabetic pregnancy might be
      contributed to by an increase in this factor.

PMID- 8254300
TI  - Regulation of secreted protein production by filamentous fungi: recent
      developments and perspectives.

PMID- 8254301
TI  - Proteolysis and orientation in Dictyostelium slugs.
AB  - It has been long known that the migrating slugs of the cellular slime moulds are
      highly sensitive to their environment and orient towards light and in temperature
      and chemical gradients. There is considerable evidence from past work that these
      orientations are governed by NH3 which affects the rate of movement of cells
      within the slug with such precision that orientation to the external stimuli is
      achieved. In order to test this hypothesis further, various ways to alter the
      internal NH3 concentration were devised. Substances that either increased or
      decreased proteolysis were applied to one side of the tip of a slug, thereby
      affecting its orientation. Some of the treatments strongly support the role of
      internally produced NH3 in orientation, and all the treatments produce results
      that are consistent with the hypothesis.

PMID- 8254302
TI  - Protection by sterols against the cytotoxicity of syringomycin in the yeast
      Saccharomyces cerevisiae.
AB  - A brief exposure (ca 20 min) of the yeast Saccharomyces cerevisiae to the
      phytotoxin syringomycin was sufficient to kill the cell. The protective effect of
      sterols against this cytotoxicity of syringomycin was investigated. Syringomycin
      was much more toxic to growing cells than to stationary-phase cells. The
      cytotoxicity of syringomycin was reduced in an environment containing sterols.
      Cytotoxicity of syringomycin at 3 micrograms ml-1 (ca 2.5 microM) was completely
      abolished by the simultaneous presence of 10 microM-cholesterol in the medium.
      Cholesterol acetate had no protective effect. Ergosterol, sitosterol and
      stigmasterol also protected against syringomycin, but they were less effective
      than cholesterol. The protective effect of sterols against the action of
      syringomycin is consistent with our hypothesis that membrane ergosterol is a
      critical component for syringomycin-binding as suggested by recent genetic
      studies.

PMID- 8254303
TI  - Growth-phase-dependent expression of the lipolytic system of Acinetobacter
      calcoaceticus BD413: cloning of a gene encoding one of the esterases.
AB  - Acinetobacter calcoaceticus BD413, when grown in batch culture in nutrient broth,
      produces both extracellular lipase activity and cell-bound esterase activity
      during and after the transition between exponential growth and the stationary
      phase. From a library of A. calcoaceticus DNA in Escherichia coli, plasmids were
      isolated that enabled E. coli to grow on media with tributyrin as the sole carbon
      source. Assays with model substrates classified the product of the cloned gene as
      an esterase. Via deletion analysis, the esterase gene was mapped on a 1.8 kbp
      chromosomal DNA fragment. This fragment was sequenced and found to contain one
      open reading frame, termed estA, which encodes a protein of 40.0 kDa. The amino
      acid sequence of this protein shows homology to a number of lipolytic enzymes,
      most notably to esterases. Deletion of estA only partially abolished cell-bound
      esterase activity in A. calcoaceticus, indicating that BD413 forms at least two
      esterases. Both esterases show the same temporal regulation of expression. beta
      Galactosidase activity was measured in strains in which a promoterless lacZ gene
      was inserted into estA. Induction of lacZ expression in these strains also
      occurred at the end of exponential growth in batch cultures, indicating that
      production of the esterase is regulated at the genetic level.

PMID- 8254304
TI  - Identification of two distinct NADH oxidases corresponding to H2O2-forming
      oxidase and H2O-forming oxidase induced in Streptococcus mutans.
AB  - Two distinct NADH oxidases, corresponding to H2O2-forming and H2O-forming enzymes
      were purified to homogeneity from Streptococcus mutans and their basic properties
      determined. The H2O2-forming enzyme was a tetramer with a subunit molecular mass
      of about 56 kDa and required flavin adenine dinucleotide (FAD) for full activity.
      The enzyme had an isoelectric point of 6.6 and exhibited optimal activity at pH
      6.0. The H2O-forming enzyme was a monomer with a molecular mass of 50 kDa and
      activity independent of exogenously added flavin. The enzyme had an isoelectric
      point of 4.8 and exhibited optimal activity between pH 7.0 and 7.5. Both enzymes
      oxidized NADH (Km 0.05 and 0.025 mM for the H2O2- and H2O-forming enzyme,
      respectively) but not NADPH and contained 1 mol of FAD per monomer. Spectra of
      the oxidized enzymes exhibited maxima at 271, 383 and 449 nm for the H2O2-forming
      enzyme and 271, 375 and 447 nm for the H2O-forming enzyme. Antibodies raised
      against the H2O2-forming enzyme or the H2O-forming enzyme reacted with their
      corresponding antigen, but did not cross-react. The amino-terminal regions of the
      two enzymes had completely different amino acid sequences.

PMID- 8254305
TI  - The distribution of the outer gas vesicle protein, GvpC, on the Anabaena gas
      vesicle, and its ratio to GvpA.
AB  - Previous studies have shown that gas vesicles isolated from the cyanobacterium
      Anabaena flos-aquae contain two types of protein, GvpA, a small hydrophobic
      protein that forms the main ribbed structure, and GvpC, a protein comprising five
      repeats of a 33-amino-acid-residue motif, which is located on the outer surface
      of the GvpA shell. GvpC was shown to increase the critical collapse pressure of
      the gas vesicles; it was thought to do this by forming a series of molecular ties
      that bind the ribs together. We now show that antibodies raised against GvpC
      label both the central cylinders and the conical end caps of native gas vesicles
      but fail to bind to gas vesicles that have been stripped of GvpC. The molar ratio
      of GvpA to GvpC has been calculated from amino acid analyses of gas vesicle
      hydrolysates by reference to the abundance of amino acids that occur
      predominantly or exclusively in one protein or the other; the molar ratio was
      found to be 25:1 in freshly isolated gas vesicles and 23:1 in gas vesicles
      saturated with GvpC. We have considered three ways in which the 33-residue
      repeats of GvpC might interact with the crystallographic unit cell of GvpA
      molecules in the ribs. The Anabaena GvpC will bind to and restore the strength of
      gas vesicles isolated from Aphanizomenon and Microcystis that lack their native
      GvpC.

PMID- 8254306
TI  - Formation of melanin pigment by a mutant of Bacillus thuringiensis H-14.
AB  - A mutant of Bacillus thuringiensis H-14 produced a dark brown pigment during
      sporulation. Production of the pigment depended on the nutritional properties of
      the growth medium. The pigment was identified as melanin, based on chemical tests
      and its infra-red spectrum. Incorporation of L-tyrosine in the culture medium
      enhanced the level of melanin production, and L-3,4-dihydroxyphenylalanine (L
      DOPA) was detected in the culture broth during the late-exponential phase of
      growth. This indicates that the pathway of melanin synthesis is from L-tyrosine,
      via L-DOPA, to melanin.

PMID- 8254307
TI  - New derivatives of TOL plasmid pWW0.
AB  - Two new segregants, PPW1-1 and PPW161-1, of Pseudomonas putida were isolated from
      the stock cultures PaW85(pWW0) and PaW85(pWW0-161). Strain PPW1-1 had lost its
      ability to grow on m-xylene but was able to grow on m-toluate. A deletion of the
      left-hand of transposon Tn4651, including the upper-operon genes, had taken place
      in plasmid pWW0mut1, isolated from strain PPW1-1. Additional deletions were
      observed in pWW0mut1 after 'benzoate-curing' (plasmids pWW0mut15, pWW0mut19,
      pWW0mut27). The genes of the upper-operon and beginning of the meta-operon were
      deleted from pWW0-161mut1, isolated from strain PPW161-1. Despite this deletion,
      cells of PPW161-1 grew on all normal TOL plasmid substrates. The Tol+ phenotype
      was stable in cells of PPW161-1 growing on benzoate. We propose that this is
      because in cells of strain PPW161-1 the catabolic genes deleted from pWW0-161mut1
      were integrated into the chromosome at the site where the (chromosomally encoded)
      ortho-pathway genes are located, resulting in the inability of the cells to use
      this pathway.

PMID- 8254308
TI  - Formation of linear plasmid multimers promoted by the phage lambda Red-system in
      lon mutants of Escherichia coli.
AB  - We report here the formation of plasmid linear multimers promoted by the Red
      system of phage lambda using a multicopy plasmid comprised of lambda red alpha
      and red beta genes, under the control of the lambda cI857 repressor. Our
      observations have revealed that the multimerization of plasmid DNA is dependent
      on the red beta and recA genes, suggesting a concerted role for these functions
      in the formation of plasmid multimers. The formation of multimers occurred in a
      recBCD+ sbcB+ xthA+ lon genetic background at a higher frequency than in the
      isogenic lon+ host cells. The multimers comprised tandem repeats of monomer
      plasmid DNA. Treatment of purified plasmid DNA with exonuclease III revealed the
      presence of free double-chain ends in the molecules. Determination of the size of
      multimeric DNA, by pulse field gel electrophoresis, revealed that the bulk of the
      DNA was in the range 50-240 kb, representing approximately 5-24 unit lengths of
      monomeric plasmid DNA. We provide a conceptual framework for Red-system-promoted
      formation and enhanced accumulation of plasmid linear multimers in lon mutants of
      E. coli.

PMID- 8254310
TI  - Genotypic typing and phylogenetic analysis of Salmonella paratyphi B and S. java
      with IS200.
AB  - Salmonella paratyphi B and Salmonella java are biovars of common serotype
      1,4,[5],12:b:1,2 which respectively cause human paratyphoid fever and
      gastroenteritis. In order to define genotypes and phylogenetic relationships in
      this group, we examined representative strains for restriction fragment length
      polymorphisms (RFLPs) in and around the 16S ribosomal RNA (rrn) genes, and the
      five to eleven insertion sites of the Salmonella-specific DNA insertion sequence
      IS200. One of four 16S rrn profiles was predominant, and was shared by the
      majority of strains, irrespective of their designation as S. paratyphi B or S.
      java. On the other hand, thirteen unique IS200 profiles were found and this
      technique was able to distinguish, for the first time, distinct genotypes for S.
      paratyphi B and S. java. One of the S. paratyphi B profiles, Spj-IP1.0,
      represented a globally-distributed clone. Greater diversity was detected within
      IS200 profiles of S. java than within those of S. paratyphi B. IS200 profiles
      described a phylogenetic complex in which strains of both biovars could be
      placed. They constituted reproducible molecular fingerprints, which could be
      compared in a band-matching database suitable for molecular epidemiological
      typing.

PMID- 8254309
TI  - Cloning and sequencing of a gene encoding acidophilic amylase from Bacillus
      acidocaldarius.
AB  - Two starch-degrading enzymes produced by Bacillus acidocaldarius (renamed as
      Alicyclobacillus acidocaldarius) were identified. According to SDS-PAGE, the
      apparent molecular masses of the enzymes were 90 and 160 kDa. Eight peptide
      fragments and the N-terminal end of the 90 kDa polypeptide were sequenced. An
      oligonucleotide, based on the amino acid sequence of a peptide fragment of the 90
      kDa protein, was used to screen a lambda gt10 bank of B. acidocaldarius, and the
      region encoding the 90 kDa protein was cloned. Unexpectedly, the ORF continued
      upstream of the N terminus of the 90 kDa protein. The entire ORF was 1301 amino
      acids (aa) long (calculated molecular mass 140 kDa) and it was preceded by a
      putative ribosomal binding site and a promoter. Computer analysis showed that the
      1301 aa protein was closely related to an alpha-amylase-pullulanase of
      Clostridium thermohydrosulfuricum. We suggest that the starch-degrading 160 kDa
      protein of B. acidocaldarius is an alpha-amylase-pullulanase, and the 90 kDa
      protein is a cleavage product of the 160 kDa protein. Another ORF, apparently in
      the same transcription unit, was found downstream from the amylase gene. It
      encoded a protein that was closely related to the maltose-binding protein of
      Escherichia coli.

PMID- 8254311
TI  - fliU and fliV: two flagellar genes essential for biosynthesis of Salmonella and
      Escherichia coli flagella.
AB  - The possible functions of two recently described flagellar genes, fliU and fliV,
      have been examined. Introduction of gene fliC, encoding the bacterial flagellin
      protein, into a number of flagellin-deficient Salmonella and Escherichia coli
      strains failed to complement the mutations in these strains, and the FliC
      flagellin was accumulated in the bacterial cytoplasm. Complementation with fliU
      and fliV, which map downstream of fliC, restored motility to some of the mutants
      which became flagellated. After inactivation of either fliU or fliV, such
      complementation no longer occurred and the flagellin protein accumulated in the
      cytoplasm, which suggested that both genes are required for the secretion of
      flagellin and expression of motility. Expression of these genes from high copy
      number plasmids resulted in the synthesis of exceptionally long flagella and in
      detection of the FliV protein on polyacrylamide gels.

PMID- 8254312
TI  - Nucleic acid sequence-based amplification (NASBA) for the identification of
      mycobacteria.
AB  - Nucleic acid sequence-based amplification (NASBA), an isothermal amplification
      technique for nucleic acids (NA), was investigated for the species-specific
      identification of mycobacteria. A set of primers was selected from a highly
      conserved region of the 16S rRNA sequence of mycobacteria sandwiching a variable
      sequence to perform amplification of mycobacterial RNA. Species-specific probes
      for the M. tuberculosis complex, M. avium-paratuberculosis, M. intracellulare and
      M. leprae were hybridized in-solution with the amplified nucleic acids of 10
      pathogenic mycobacteria and 11 closely related bacteria, as well as with human
      derived NA in an enzyme-linked gel assay (ELGA). Each probe was shown to
      hybridize specifically to the amplified single-stranded RNA of the corresponding
      species. Thirty-two clinical isolates of M. tuberculosis strains from different
      parts of the world were correctly identified by NASBA using the M. tuberculosis
      complex-specific probe. In combination with the ELGA, NASBA could identify
      mycobacteria rapidly, i.e. in less than 6 h. The relative simplicity and rapidity
      of this technique makes it an attractive tool for species-specific identification
      of mycobacteria.

PMID- 8254313
TI  - Use of a triplex polymerase chain reaction for the detection and differentiation
      of Mycoplasma pneumoniae and Mycoplasma genitalium in the presence of human DNA.
AB  - PCR primers corresponding to the adhesin genes of Mycoplasma pneumoniae and
      Mycoplasma genitalium were shown to detect the corresponding organisms
      specifically. Absence of cross-reaction with seven other mollicute species and
      six unrelated bacterial species commonly found in humans was demonstrated.
      Positive control primers directed against human mitochondrial DNA could be mixed
      with the Mycoplasma primers without loss of specificity or sensitivity. A
      detection level of 10 c.f.u. of either Mycoplasma species could be readily
      obtained, even in the presence of 10(4) human cells. The triplex PCR method
      developed is very simple and does not require hybridization or the use of
      radioisotopes and allows detection and differentiation of these mycoplasmas
      against the background of human DNA found in clinical specimens.

PMID- 8254314
TI  - Variation in the size of the ospA-containing linear plasmid, but not the linear
      chromosome, among the three Borrelia species associated with Lyme disease.
AB  - The aetiological agents of Lyme disease form a phylogenetically heterogeneous
      group, composed of three species, Borrelia burgdorferi, Borrelia garinii, and
      group VS461. We have compared the sizes of the linear plasmid that carries the
      genes encoding the major outer-surface proteins OspA and OspB as well as the size
      and structure of the chromosome among the Lyme disease spirochaetes. We have
      found differences in the sizes of the ospA-containing plasmids, but not the
      linear chromosomes among the three species. The ospA-containing plasmid size of
      50 kb in B. burgdorferi isolates is significantly smaller than the size of 55 kb
      in B. garinii isolates and 56 kb in group VS461 isolates. The chromosome was
      found to be linear in all three Borrelia species, but not significantly different
      in size.

PMID- 8254316
TI  - Construction of Bacillus anthracis mutant strains producing a single toxin
      component.
AB  - The two protein exotoxins secreted by Bacillus anthracis are composed of three
      distinct components: protective antigen (PA), lethal factor (LF), and (o)edema
      factor (EF). We have developed a genetic strategy that permits us selectively to
      inactivate each of the genes coding for PA, EF or LF. This strategy involved the
      deletion of a portion of the structural gene and the insertion of an antibiotic
      resistance cassette. With this technique, double mutant strains of B. anthracis
      producing only one toxin component have been constructed. Characterization of the
      mutant strains indicated that they produced the expected single toxin protein.
      Using a simple, two-step protocol, we have purified PA, LF and EF to homogeneity
      from culture supernatants. These three mutant strains are potentially powerful
      tools for studying the individual effect of each toxin component in vitro and in
      vivo.

PMID- 8254315
TI  - Albumin-binding proteins on the surface of the Streptococcus milleri group and
      characterization of the albumin receptor of Streptococcus intermedius C5.
AB  - Members of the Streptococcus milleri group (SMG) that react with Lancefield group
      C antisera were shown to bind large amounts of albumin although there was no
      direct relation between these two properties as polyclonal antisera to Lancefield
      group C antigen did not prevent the binding of albumin. There was a specificity
      for albumin binding, with albumin from man, monkeys, cat, dog and mouse being
      bound to a greater degree than albumin from cow, horse, goat or rabbit. Gold
      labelled albumin was shown to be located close to the surface of strains by
      transmission electron microscopy. A cell-surface protein of M(r) 24,000, which
      was liberated by lysozyme treatment of cells, was shown to be the cell-surface
      receptor on Streptococcus intermedius C5. The receptor was physically dissimilar
      from protein G, an albumin- and IgG-binding protein of 'large-colony' Lancefield
      group C and G streptococci.

PMID- 8254317
TI  - Targeting of interleukin-2 to the periplasm of Escherichia coli.
AB  - A synthetic gene coding for interleukin-2 (IL-2) was used to produce large
      amounts of recombinant IL-2 (met-IL-2) in Escherichia coli. Met-IL-2 was found to
      accumulate in the cytoplasm in an insoluble, aggregated form. Inclusion bodies
      located at the pole caps of cells were detected using immunogold labelling.
      Constructs were designed to fuse the IL-2 gene to DNA fragments encoding signal
      peptides for an outer-membrane protein (OmpA) or for a periplasmic protein (PhoA)
      of E. coli. No significant maturation was observed with these fusion proteins
      which were found in an insoluble form in the cytoplasm. The influence of charge
      disposition at the N-terminus of the mature portion of the protein was
      investigated by replacing positively charged amino acids with glutamic acid. None
      of the introduced substitutions had any effect. Various factors that might affect
      expression, secretion and folding were examined in an attempt to obtain
      secretion. By fusing IL-2 to the precursor maltose-binding protein (preMBP) a
      large fraction of the preMBP-IL-2 protein was correctly processed and transported
      to the periplasmic space. IL-2 derived from MBP-IL-2 after FXa cleavage possessed
      similar specific activity to recombinant IL-2 produced in Chinese Hamster ovary
      cells.

PMID- 8254318
TI  - Cloning, nucleotide sequence and characterization of the mannitol dehydrogenase
      gene from Rhodobacter sphaeroides.
AB  - Transposon mutagenesis and antibiotic enrichment were employed to isolate a
      mutant of Rhodobacter sphaeroides Si4 designated strain M22, that had lost the
      ability to grow on D-mannitol and to produce the enzyme mannitol dehydrogenase
      (MDH). DNA flanking the transposon in the mutant strain was used as a probe for
      the identification and cloning of the MDH gene (mtlK). A 5.5 kb EcoRI/BglII
      fragment from R. sphaeroides Si4 was isolated and shown to complement the
      mutation in R. sphaeroides M22. Successful complementation required that a
      promoter of the vector-plasmid pRK415 be present, suggesting that the mtlK gene
      is part of a larger operon. Using oligonucleotides derived from the N-terminal
      sequence of MDH as probes mtlK was located on the complementing fragment and the
      gene was sequenced. The mtlK open reading frame encodes a protein of 51,404 Da
      with an N-terminal sequence identical to that obtained from amino acid analysis
      of the purified MDH. The MDH of R. sphaeroides Si4 exhibits distant similarity to
      the mannitol-1-phosphate dehydrogenases from Escherichia coli and Enterococcus
      faecalis, with 28.1% and 26.3% identity, respectively. Mutant strains deficient
      in MtlK displayed substantial levels of sorbitol dehydrogenase activity,
      originally thought to be only a minor activity associated with the MDH enzyme. It
      is likely that we have uncovered an additional polyol dehydrogenase with activity
      for sorbitol. The mtlK gene can be used for overexpression of MDH in E. coli in
      order to obtain sufficient amounts of enzyme for further investigations and
      applications.

PMID- 8254319
TI  - Transformation of Helicobacter pylori by chromosomal metronidazole resistance and
      by a plasmid with a selectable chloramphenicol resistance marker.
AB  - Most strains of Helicobacter pylori are naturally competent for uptake of
      chromosomal DNA. Transformation frequencies for streptomycin resistance or
      rifampicin resistance markers ranged from 1 x 10(-4) to 1 x 10(-3) per viable
      cell using a plate transformation procedure. Transformation of a metronidazole
      resistance marker (MtrR) was demonstrated when either a laboratory-derived mutant
      or a MtrR clinical isolate were used as the source of donor DNA. MtrR was
      transformed at a frequency of 3 x 10(-5) per viable cell. All H. pylori strains
      tested produce large amounts of DNAase, which may reduce DNA available for
      transformation. Four H. pylori plasmids were isolated. DNA fragments from H.
      pylori plasmids were deleted or rearranged when cloned in pUC19 and propagated in
      Escherichia coli DH5 alpha. An H. pylori plasmid, pUOA26 which contained a
      chloramphenicol resistance determinant from Campylobacter coli, was constructed
      in H. pylori. This plasmid could be successfully introduced by natural
      transformation only into H. pylori recipients which contained a homologous
      resident plasmid. Transformation of pUOA26 into plasmid-free cells of H. pylori
      was achieved by electroporation. Transformation frequencies were 1 x 10(-4)
      transformants per viable cell when plasmid DNA was isolated from the same strain;
      however, introduction of pUOA26 DNA derived from H. pylori 8091 into a different
      H. pylori strain, NCTC 11639, resulted in transformation at much lower
      frequencies (< or = 1 x 10(-7) per viable cell).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254320
TI  - Helicobacter canis sp. nov., a new species from dogs: an integrated study of
      phenotype and genotype.
AB  - A group of Campylobacter-like organisms (CLOs) were isolated from the faeces of
      diarrhoeic or healthy dogs, constituting 4% of all CLOs from this source. Since
      they formed a unique DNA homology group within the genus Helicobacter, and
      exhibited distinctive phenotypic properties, they were collectively termed the HC
      group. A polyphasic taxonomic analysis was made of this group. The phenotype of
      four dog isolates and a single human isolate was unique and could be
      distinguished bacteriologically from other helicobacters. Electron microscopic
      ultrastructure revealed defining characteristics of Helicobacter. The 16S rRNA
      gene of the nominated type strain NCTC 12739T was sequenced, and its analysis
      delineated the group as a new species of Helicobacter. This conclusion was
      supported by relative DNA homology and whole-cell protein electrophoretic
      patterns. We therefore propose the name Helicobacter canis sp. nov. for this
      group. The species most closely related to H. canis sp. nov. were H. cinaedi,
      'Flexispira rappini' and H. fennelliae. A species-specific recombinant DNA probe
      was cloned from NCTC 12739T for use in routine laboratory identification and
      epidemiological studies. The faecal source, bile tolerance and lack of urease
      activity of H. canis sp. nov. suggest that this new Helicobacter species
      colonizes the lower bowel rather than the stomach.

PMID- 8254321
TI  - The temperate phages RP2 and RP3 of Streptomyces rimosus.
AB  - The oxytetracycline-producing Streptomyces rimosus strains R6-65 and R7 (ATCC
      10970) are lysogenic for the two narrow-host-range phages RP2 and RP3. Both
      phages are released at low frequency from the lysogenic strains and form plaques
      on 'cured' S. rimosus strains. RP2 and RP3 are of similar shape with flexible
      tails and contain double-stranded DNA of about 70% G+C with cohesive ends (group
      B1 of bacteriophage classification). The two phages also have identical, very
      slow, growth kinetics in S. rimosus, with a latent phase of about 6 h and a rise
      period of about 4 h. RP2 and RP3 are heteroimmune and they differ slightly in
      their size of phage particles and length of DNA (64.7 and 62.4 kb for RP2 and
      RP3, respectively). The restriction maps of the two phages are completely
      different, and hybridization experiments showed only one short region of sequence
      similarity (less than 430 bp); the two phages are thus essentially unrelated.
      Both phages lysogenize their hosts by recombination via defined attachment (att)
      sites. The positions of the attP sites have been localized on the restriction
      maps of RP2 and RP3 to restriction fragments of 800 and 300 bp, respectively. The
      prophages did not affect the level of oxytetracycline production or the genetic
      instability of this trait.

PMID- 8254322
TI  - Severity as a key construct in depression.
AB  - Mild, moderate, and severely depressed subgroups were operationally defined in a
      sample of hospitalized patients clinically diagnosed as depressed. Women were
      overrepresented among the severely depressed patients, but no other demographic
      differences among subgroups were found. Generalized anxiety and psychic
      disorganization were significantly more pronounced in patients who were severely
      depressed. Severely depressed people also reported more role-performance
      impairments than did those who were less seriously depressed. Among women, a
      secondary diagnosis of substance abuse was present significantly less often in
      the severely depressed. Based on self-reports at admission and 4 weeks later,
      marked improvement was seen only among the moderately depressed. There was not a
      statistically significant symptom change in the mildly depressed group; for the
      severely depressed, the change over time was significant but the patients
      remained highly symptomatic. The authors discuss the importance of the construct
      of severity for clinical practice, hospital policy, and future research.

PMID- 8254323
TI  - Categorization of major depression in an outpatient sample.
AB  - Intake Beck Depression Inventory (BDI) item scores of 400 outpatient major
      depressives were submitted to a categorization algorithm developed for artificial
      intelligence applications. The algorithm maximizes a function of "category
      utility" that is preferable in several respects to available clustering methods,
      and has demonstrated its capacity to locate the most informative, or "basic,"
      level of categorization. The analysis yielded four syndromal subtypes: a common,
      general depressive type; a common and relatively severe melancholic type; an
      infrequent type characterized by self-critical features, generalized anxiety, and
      an absence of melancholic features; and an infrequent, mild type distinguished by
      enervation and anhedonic features. Implications for the classification of
      depression are discussed.

PMID- 8254324
TI  - Crisis intervention in depressed patients with and without DSM-III-R personality
      disorders.
AB  - We compared the relationships between response to a crisis intervention program
      and long-term outcome in 31 depressed outpatients with and without DSM-III-R
      personality disorders (PD). The presence of PD predicted a poorer 2-year outcome.
      PD subjects with better working alliance and increased insight at termination of
      crisis intervention had increased compliance with long-term psychiatric treatment
      (p < .005) and better 2-year outcome (p < .005). Increased compliance with long
      term psychiatric treatment predicted better long-term outcome in PD patients (p <
      .005). None of these significant relationships was observed in the comparison
      group without PD, suggesting that establishing an effective treatment process may
      be especially important for outcome in PD patients.

PMID- 8254325
TI  - The heterogeneity of schizophrenic information processing and negative versus
      positive symptoms.
AB  - In this study, 20 schizophrenic patients were subdivided into a schizophrenia
      group with positive symptoms (N = 11) and a schizophrenia group with negative
      symptoms (N = 9) by Andreasen's rating scales: the Scale for the Assessment of
      Negative Symptoms and the Scale for the Assessment of Positive Symptoms. These
      groups were compared with 17 normal controls and 17 subjects with a closed head
      injury. Indices of information processing derived from Coglab, a
      multiparadigmatic cognitive test battery developed by Spaulding et al., were used
      for comparison. The "negative" schizophrenia subjects were characterized by a
      more pervasive deficient information-processing capacity than the "positive"
      schizophrenia subjects. The deficits both groups had in common were, however, not
      of equal severity. The closed head injury group, who served as an indirect
      control for the presumed generalized deterioration in the negative schizophrenia
      group, did not compare very well to this latter group. The results are discussed
      in relation to the question of whether the information-processing deficiencies
      stem from a single causal process, or whether these deficiencies are independent
      and associated with many etiological pathways.

PMID- 8254326
TI  - A dimensional and categorical approach to the symptomatology of recent-onset
      schizophrenia.
AB  - Sixty-five patients with recent-onset schizophrenia were assessed with two widely
      used symptom scales, the Brief Psychiatric Rating Scale-Expanded (BPRS-E) and the
      Psychiatric Assessment Scale (Manchester scale). Principal components analysis of
      the BPRS-E scores yielded a four-dimensional structure: positive symptoms,
      negative symptoms, disorganization, and depression. With the Psychiatric
      Assessment Scale, three dimensions were found: the positive symptoms (delusions,
      hallucinations) and disorganization (incoherence) appeared in one dimension. A
      categorical analysis resulted in predominantly positive, negative, and
      disorganized clusters, but more than half of the sample could not be allocated to
      any of these groups.

PMID- 8254327
TI  - Communication deviance, attention, and schizotypy in parents of schizophrenic
      patients.
AB  - Singer and Wynne's measures of communication deviance were adapted for use with
      conversational speech and applied to audiotaped speech samples of schizophrenic
      patients, their parents, and matched nonpsychiatric control subjects. The parents
      demonstrated levels of language disturbance similar to those of the patients and
      higher than those of controls. Language deviance in the parents was positively
      associated with distractibility on a matched-task digit-span measure of attention
      and with severity scores on a separate schizotypy scale. These findings are
      discussed with respect to possible cognitive variables underlying the language
      disturbances and their potential relevance to schizophrenic etiology.

PMID- 8254328
TI  - The cost effectiveness of crisis intervention. Admission diversion savings can
      offset the high cost of service.
AB  - The authors sought to determine whether a mobile crisis intervention service can
      effect cost savings by diverting patients from hospital admission into community
      based treatment. They followed 50 consenting adult psychiatric patients for 6
      months from the first day they were seen by the crisis intervention service. At
      the first visit, the crisis team obtained data to assess each patient's degree of
      risk for hospitalization. Investigators then kept a day-by-day record of every
      psychiatric treatment received by each patient, in an effort to determine the
      cost effectiveness of crisis intervention. The authors present evidence that
      crisis intervention permits some patients who would otherwise have been
      hospitalized to remain in the community and that savings thus realized exceed the
      expense of crisis intervention.

PMID- 8254329
TI  - Repetitive behaviors in schizophrenic patients admitted to an acute-care unit: a
      replicative study.

PMID- 8254330
TI  - A case of chronic haircutting.

PMID- 8254331
TI  - Posttraumatic stress disorder postpsychosis.

PMID- 8254332
TI  - Sequence selective coordination of Mg2+(aq) to DNA.
AB  - Thermodynamic parameters for magnesium binding to a series of DNA molecules of
      defined sequence have been evaluated by 25Mg NMR spectroscopy. These results
      demonstrate that G/C-DNA binds Mg2+(aq) up to 40 to 100-fold more strongly than
      A/T-DNA, i.e., coordination of Mg2+(aq) to G/C-DNA is ca. 2.1-2.7 kcal (mole
      Mg2+)-1 more stable relative to A/T-DNA. Activation free energies [delta G*
      approximately (12.7-13.3) x 10(3) kcal] and exchange rates [k(ex) approximately
      (0.5-3.0) x 10(3)s-1] were estimated by variable temperature experiments. The low
      value of the quadrupole coupling constants (chi B = 0.2-0.6 MHz) is indicative of
      outer-sphere coordination by Mg(H2O)6(2+).

PMID- 8254333
TI  - Self-similarity of Mn(II)-induced trypsin activity oscillations. Experimental
      evidence.
AB  - Aperiodic self-similar oscillations of trypsin activity were shown by experiments
      conducted in the presence of Mn2+ ion at pH 8.2 and -10 degrees C in frozen (cryo
      oscillations) and at 0 degrees and 25 degrees C under unstirred conditions,
      respectively. The solution of trypsin obtained by trypsinogen activation and of
      0.1 M MnCl2 was distributed into samples or kept in batches at the experimental
      temperature and sampled. At given time intervals the samples were tested for
      tryptic activity. In experiments at -10 degrees C the samples were frozen at the
      initiating of the series. The irregular shapes of activity curves as well as the
      trajectory of a next-amplitude plot is discussed as a result of a sensitive
      coupling between the chemical/conformational and diffusional controls of the
      enzyme activity in the far-from-equilibrium heterogeneous system. These indicate
      that the self-similar character of the trypsin activity oscillations can be
      considered on a phenomenological level.

PMID- 8254334
TI  - Metal complexes of anti-inflammatory drugs. Part VIII: Suprofen complex of
      copper(II).
AB  - The preparation and properties of the copper(II) complex Cu(SUP)2.H2O are
      reported for the anti-inflammatory drug Suprofen (SUP). The diffuse reflectance
      spectra and magnetic moment are consistent with a dinuclear structure as found
      for [Cu(aspirinate)2(H2O)]2. The copper(II) complex exhibits an increased
      superoxide dismutase activity compared with the parent drug molecule in the
      nitroblue tetrazolium assay.

PMID- 8254335
TI  - Synthesis, characterization, and antioxidative activity of new vitamin B6
      triethanolamine rare earth (III) complexes.
AB  - A series of new vitamin B6 triethanolamine rare earth (III) complexes
      Re(PN)3(TEA)(NO3)2Cl (PN = pyridoxol; TEA = triethanolamine; Re = La1, Ce2, Pr3,
      Nd4, Sm5, Tb6, Dy7, Ho8, Er9, Y10), were synthesized and characterized by
      elemental analysis, molar conductance, TGA-DTA, UV, IR, and 1H NMR spectroscopic
      techniques. The suppression ratio of complexes for the hydroxyl radical (OH.) and
      the superoxide radical (O2-.) were determined, the results show that these
      complexes possess scavenging effects on OH. and O2(-.). In this paper we also
      discuss the effect of complex conc. for the suppression ratio on superoxide
      radical O2(-.).

PMID- 8254336
TI  - Synthesis, characterization, and antioxidative activity of vitamin B6 rare earth
      (III) complexes.
AB  - A series of vitamin B6 pyridoxol rare earth (III) complexes Re(PN)5Cl3. 6H2O (PN
      = pyridoxol; Re = La, Ce, Pr, Nd, Sm, Eu, Gd, Ho, Er, Y) were synthesized and
      characterized by elemental analysis, molar conductance, TGA-DTA, IR, and 1HNMR
      spectroscopic techniques. The antioxidative activity of complexes was determined,
      using the suppression ratio of activated oxygen as an indicator. The results show
      that the complexes have the scavenger effects for activated oxygen.

PMID- 8254337
TI  - Complexes of Cu(II) with Asn-Ser-Phe-Arg-Tyr-NH2; an example of metal ion
      promoted conformational organization which results in exceptionally high complex
      stability.
AB  - The pentapeptide fragment of ANF, Asn-Ser-Phe-Arg-Tyr-NH2, coordinates to Cu(II)
      using the same four nitrogen donor centers as simple pentapeptides such as
      pentaalanine yet the complexes are of much higher stability as a result of a
      highly organized side-chain structure which is present in the complex but absent
      from the free ligand.

PMID- 8254338
TI  - The binding of Yb(III) and Gd(III) to bovin serum albumin by a competitive
      spectrophotometry.
AB  - A competitive spectrophotometry has been used to study the binding of Yb(III) and
      Gd(III) to BSA. The indicator ligand, 5-Br-PAPS, as well as its metal complexes,
      ML, having intense colors with sufficiently separate absorption peaks permits the
      analysis of the interaction between metal and BSA. Experimental data are analyzed
      by using Scatchard plots. The results show that both Yb and Gd bind to BSA with
      four equivalent affinity sites at pH 6-7. Some additional lower affinity sites
      are observed for Gd but not for Yb. The slope of the plots, the apparent
      association constant of the metal with BSA, decreases with decreasing pH. The pH
      dependence of the apparent association constant indicates the 1:1 competition
      between metal ions and hydrogen ions for the binding site. The intrinsic
      association constant of the metal, KM(H-1A), and the proton association constant,
      KH(H-1A) =, are found to be logKM(H-1A) = 7.00 +/- 0.03 and log KH(H-1A) = 7.08
      +/- 0.06 for the Yb binding sites, and logKM (H-1A) = 6.16 +/- 0.08 and log KH(H
      1A) = 6.63 +/- 0.10 for the Gd binding sites by a graphical analysis (A = BSA).

PMID- 8254339
TI  - The binding of cobalt(III)-ligated amino acids and peptides to chymotrypsin and
      trypsin.
AB  - The interaction of some metal-ligated amino acids and dipeptides with
      chymotrypsin and trypsin was examined. Small structural analogues of substrates
      carrying the positively charged pentamminecobalt(III) group at the carboxyl
      terminal were synthesized. These compounds do not undergo catalytic conversion
      but were found to inhibit their target enzyme reversibly. The binding to the
      active sites was evaluated by kinetic inhibition measurements. The binding
      affinities of the metal-ligated substrate-analogues were found to be comparable
      in strength to those of more familiar small specific peptides.

PMID- 8254340
TI  - Reversal of copper(II)-induced methemoglobin formation by thiols.
AB  - Oxyhemoglobin is oxidized to methemoglobin by copper(II) in a two-stage reaction
      that results in conversion of Fe(II) to Fe(III) in heme of the beta subunits, but
      not the alpha subunits. Glutathione and other thiols, which are slowly oxidized
      by Cu(II), protect oxyhemoglobin from Cu(II)-induced oxidation. In the present
      studies, when oxyhemoglobin was first oxidized to methemoglobin by Cu(II) and
      thiols such as glutathione added to the sample, methemoglobin was reduced to
      oxyhemoglobin. Once reduction of methemoglobin stopped, as the thiol was
      oxidized, the oxyhemoglobin formed was reoxidized by Cu(II). The addition of the
      same thiols to methemoglobin formed by autoxidation did not reduce it to
      oxyhemoglobin. The addition of thiols such as cysteine, which are rapidly
      oxidized by Cu(II), to methemoglobin formed by incubation with Cu(II) also
      resulted in reduction of methemoglobin, but the period of reversal was much
      shorter than that seen with glutathione and other less reactive thiols. When
      cysteine and glutathione were added together to Cu(II)-induced methemoglobin, the
      rate of reduction and reoxidation was intermediate to that seen when either was
      added separately. When EDTA was added to a system in which oxyhemoglobin was
      undergoing Cu(II)-induced oxidation, oxidation of oxyhemoglobin ceased and there
      was no reduction of the methemoglobin to oxyhemoglobin. When both glutathione and
      EDTA were added to this system, the response was the same as with EDTA alone,
      suggesting that Cu(I) or (II) may be required for the reduction of copper-induced
      methemoglobin by thiols. These studies show that thiols that are slowly oxidized
      by Cu(II) both protect oxyhemoglobin from Cu(II)-induced oxidation, and reduce
      the methemoglobin formed to oxyhemoglobin.

PMID- 8254341
TI  - New platinum(II) complexes of beta-cyclodextrin diamine derivatives and their
      antitumor activity.
AB  - The new platinum(II) complexes of beta-cyclodextrin functionalized at the primary
      position with ethylenediamine or with propylenediamine were synthesized and
      characterized by mass spectrometry, electronic spectrophotometry, and
      multinuclear NMR spectroscopy. Platinum(II) complexation makes the cavity more
      asymmetric. These complexes were tested in vitro for their cytotoxic activity.
      The relevance of the low activity observed regarding the interaction between the
      cell and the cyclodextrin cavity is discussed.

PMID- 8254342
TI  - Characterization of heme c peptides by mass spectrometry.
AB  - Liquid secondary ion mass spectrometry, also called fast atom bombardment mass
      spectrometry, has been used to determine proteolytic hydrolysis sites for
      peptides derived from c-type cytochromes that contain covalently attached heme c.
      An unexpected fragmentation occurs that breaks the covalent thioether bonds
      between the heme and the peptide, and the heme fragment further rearranges to
      give rise to an intense ion at m/z of 617 that corresponds to protonated iron
      protoporphyrin IX. The observation of this ion fragment can be used to
      unambiguously identify the presence of authentic heme c in peptides or peptide
      mixtures at the subnanomole level.

PMID- 8254343
TI  - Further isolation of glycosides from Cynanchum hancockianum.
AB  - Three new glycosides, neohancosides B, C, and D, have been isolated as
      polyacetates 2, 3, and 4 from Cynanchum hancockianum along with neohancoside A
      hexaacetate [1]. The new compounds were established as 9-hydroxylinalool-3-O-beta
      D-xylopyranosyl-(1-->6)-beta-D-glucopyr anoside heptaacetate [2], 2
      hydroxyacetophenone-2-O-beta-D-xylopyranosyl-(1-->6)-beta-D-gluc opyranoside
      hexaacetate [3], and 6'-O-sinapoylsucrose octaacetate [4] by means of
      spectroscopic and chemical tools.

PMID- 8254344
TI  - An antifungal bibenzyl from the New Zealand liverwort, Plagiochila
      stephensoniana. Bioactivity-directed isolation, synthesis, and analysis.
AB  - The bioactivity-directed isolation of 4-hydroxy-3'-methoxybibenzyl [1] from a New
      Zealand liverwort, Plagiochila stephensoniana, is described. Compound 1 exhibited
      antifungal and antibacterial activity. Compound 1 is not considered to be a
      useful taxonomic marker. Syntheses of 1, stilbenes 2 and 3, and some derivatives
      were made and the biological activities were compared.

PMID- 8254345
TI  - A screen for inhibitors of DNA recombination: identification of two new
      spirostanol glycosides from Chamaedorea linearis.
AB  - Two new glycosides have been isolated from the MeOH extract of the stem wood and
      stem bark of an Ecuadorian plant Chamaedorea linearis, and their structures have
      been determined by spectroscopic means and X-ray analysis of the aglycone to be 1
      O-[beta-L-fucopyranosyl-(4'-sulfate)]-25R,5 alpha-spirostane-1 beta, 3 beta-diol
      [1]) and 1-O-[beta-L-fucopyranosyl-(4'-sulfate)]-25R,5 alpha-spirostane-1 alpha,
      3 beta-diol [2]. These compounds were identified in a screen for inhibitors of
      recombinational DNA repair. Cytotoxic activity was also demonstrated.

PMID- 8254346
TI  - Cytotoxic and antimalarial alkaloids from the tubers of Stephania pierrei.
AB  - Biological evaluation of extracts prepared from the tubers of Stephania pierrei
      revealed cytotoxic and antimalarial activity. During the course of separation,
      two new aporphine alkaloids, (-)-asimilobine-2-O-beta-D-glucoside [2] and (-)
      nordicentrine [8], in addition to twenty-one known isoquinoline alkaloids, were
      isolated. Each isolate was assessed for cytotoxic and antimalarial activities. It
      was found that the cytotoxicity of S. pierrei was mainly due to the presence of
      the aporphine alkaloids containing the 1,2-methylenedioxy group 3-10, whereas the
      antimalarial activity was attributed to the nonquaternary aporphine alkaloids 1,
      3-10 and the tetrahydroprotoberberines possessing a phenolic functionality, 13
      15, 18. None of the isolates showed a degree of selectivity comparable to that of
      antimalarial drugs such as chloroquine, quinine, mefloquine, and artemisinin.
      Comparison of the alkaloid content of S. pierrei and Stephania erecta strongly
      suggested separate identities for the two plants.

PMID- 8254347
TI  - Bioactive furanonaphthoquinones from Crescentia cujete.
AB  - Bioassay-directed fractionation of the MeCOEt extract of Crescentia cujete
      (Bignonaceae) resulted in the isolation of (2S,3S)-3-hydroxy-5,6
      dimethoxydehydroiso-alpha-lapachone [1], (2R)-5,6-dimethoxydehydroiso-alpha
      lapachone [2], (2R)-5-methoxydehydroiso-alpha-lapachone [3], 2-(1
      hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [4], 5-hydroxy-2-(1
      hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [5], 2-isopropenylnaphtho[2,3-b]furan
      4,9-dione [6], and 5-hydroxydehydroiso-alpha-lapachone [7]. Compounds 1-3 are
      new, and all compounds are bioactive, showing selective activity towards DNA
      repair-deficient yeast mutants. The isolation, structure elucidation, and
      biological activities of these compounds are reported.

PMID- 8254348
TI  - Selligueain A, a novel highly sweet proanthocyanidin from the rhizomes of
      Selliguea feei.
AB  - Selligueain A, a novel sweet trimeric proanthocyanidin with a doubly linked A
      unit, has been isolated from the rhizomes of Selliguea feei collected in
      Indonesia. The structure of this substance was established as epiafzelechin-(4
      beta-->8, 2 beta-->O-->7)-epiafzelechin-(4 beta-->8)-afzelechin [1], on the basis
      of a combination of spectral and chemical methods. The compound was not acutely
      toxic for mice and not mutagenic in a forward mutation assay utilizing Salmonella
      typhimurium strain TM677. Selligueain A [1] was rated by a taste panel as
      exhibiting about 35 times the sweetness intensity of a 2% w/v aqueous sucrose
      solution, and at a concentration of 0.5% w/v in H2O was perceived as pleasant
      tasting rather than astringent.

PMID- 8254349
TI  - Ethnobotanical drug discovery based on medicine men's trials in the African
      savanna: screening of east African plants for antimicrobial activity II.
AB  - Antimicrobial activity of a number of East African plants was evaluated. The
      plants collected based on information provided by medicine men showed a much
      higher probability of finding active extracts than the plants collected randomly.

PMID- 8254350
TI  - Bioconversion of arteannuin B to artemisinin.
AB  - Arteannuin B, which co-occurs with artemisinin, the potent antimalarial principle
      of the Chinese medicinal herb Artemisia annua (Asteraceae), has been converted to
      the latter using crude and semi-purified cell-free extracts of the leaf
      homogenates of the plant. Detection procedures to quantitate this bioconversion,
      including one that is novel which uses gcms, are detailed.

PMID- 8254351
TI  - Macrophyllicinin, a saponin from Primula macrophylla.
AB  - A new triterpenoid saponin, designated macrophyllicinin [1], has been isolated
      from the MeOH extract of the whole plant of Primula macrophylla. Its structure
      was established by chemical and spectroscopic means as 3 beta-O-[alpha-L
      rhamnopyranosyl-(-->2)-beta-D-glucopyranosyl-(-->2)- beta-D-galactopyranosyl-(-
      >2)-beta-D-glucuronopyranosyl]-6 beta,16 alpha-dihydroxyolean-12-en-28-acetate.
      The aglycone 2 of this saponin is also a new compound.

PMID- 8254352
TI  - Agrochemical activity and isolation of N-(4'-bromophenyl)-2,2-diphenylacetanilide
      from the Thai plant Arundo donax.
AB  - The CHCl3 extract of the whole plant of Arundo donax yielded N-(4'-bromophenyl)
      2,2-diphenylacetanilide [1]. The structure was determined on the basis of
      chemical, spectroscopic, and X-ray crystallographic data. Compound 1 has not been
      previously reported as a natural product and showed inhibition of feeding for
      boll weevils.

PMID- 8254353
TI  - Bioactive metabolites from Sicilian marine fennel, Crithmum maritimum.
AB  - Bioactivity-guided fractionation of the lipid extract of Crithmum maritimum using
      the brine shrimp lethality assay led to the isolation of three bioactive
      compounds. Two of these are known C17 polyacetylenic metabolites, falcarinol [1]
      and falcarindiol [2], previously isolated from several species of the
      Umbelliferae and Araliaceae. The third active principle was identified as O
      geranylvanillin [3], an aromatic ether described in the literature as a synthetic
      compound but unknown as a natural product. Cytotoxic activity of the pure
      compounds was significant for 1 and 2, much less intense for 3.

PMID- 8254354
TI  - Chemical constituents of Aristolochia rigida and mutagenic activity of
      aristolochic acid IV.
AB  - Two aristolochic acids [2 and 3] and a flavonol glycoside 1 have been isolated
      from Aristolochia rigida (Aristolochiaceae). Aristolochic acid IV [2], the most
      abundant constituent, has shown a weak direct mutagenic activity in the Ames
      test: this action seems to be inhibited, at least in part, by metabolic
      reactions.

PMID- 8254355
TI  - Isolation and structure elucidation of 34-sulfatobastadin 13, an inhibitor of the
      endothelin A receptor, from a marine sponge of the genus Ianthella.
AB  - 34-Sulfatobastadin 13 [1] was isolated from the sponge Ianthella sp. Its
      structure was elucidated by nmr techniques and chemical transformation to
      bastadin 13 [2]. Compound 1 weakly inhibited binding to the endothelin A receptor
      (ETA), while compound 2 inhibited growth of Bacillus subtilis.

PMID- 8254356
TI  - An antifungal compound produced by grapefruit and Valencia orange after wounding
      of the peel.
AB  - Wounding citrus induces the production of the antifungal compound 1, isolated
      from peel of injured grapefruit, Citrus paradisa, and injured orange, Citrus
      sinensis. Interpretation of ms, uv, and 1D and 2D nmr spectroscopic data led to
      the identification of the new compound as 3-[4-hydroxy,3-(3-methyl-2-butenyl)
      phenyl]-2-(E)-propenal.

PMID- 8254357
TI  - Knerachelins A and B, antibacterial phenylacylphenols from Knema furfuracea.

PMID- 8254358
TI  - The differential expression of 16 NMDA and non-NMDA receptor subunits in the rat
      spinal cord and in periaqueductal gray.
AB  - Diverse arrays of glutamate-gated channels in the spinal cord and associated
      pathways are partly responsible for sensory input, for altered sensitivity to
      peripheral stimuli during inflammation, and for generation of motor patterns. The
      expression of 16 genes, encoding all known subunits for the NMDA receptor (NR1,
      NR2A to NR2D), AMPA/low-affinity kainate (GluR-A to -D), high-affinity kainate
      ionotropic receptors (KA-1, -2, GluR-5 to -7) and two orphan receptor subunits
      (delta-1 and -2) was examined by in situ hybridization in rat lumbar spinal cord,
      and in the periaqueductal gray. Subunit mRNAs for GluR-A, -B Flip, KA-2, and NR1
      were abundant in the dorsal horn, with NR2D lightly expressed. Occasional cells
      in lamina II contained NR2C mRNA. While the GluR-A gene was preferentially
      expressed in laminae I and II-outer, GluR-B mRNA was evenly expressed throughout
      all superficial laminae (I, II-outer, II-inner, and III). Large neurons in
      laminae IV and V expressed mainly NR1, GluR-C, and to lesser extents the GluR-B,
      GluR-D, and NR2D genes. Lamina I contained occasional cells expressing the GluR-5
      gene, whereas GluR-7 mRNA was present in scattered cells in all superficial
      laminae. In motor neurons, GluR-B Flip, -C Flip, -D Flip, and NR1 mRNAs were
      expressed heavily, and those of NR2D and KA-1 weakly. Possibly connected to the
      RNA editing mechanism, GluR-B was the only subunit whose RNA was concentrated in
      motor neuron cell nuclei in addition to the cytoplasm. delta-1 and -2 mRNAs were
      found at low levels throughout the gray matter. NR2A, NR2B, and GluR-6 mRNAs were
      undetectable. For the periaqueductal gray, prominent mRNAs were GluR-A, -B, and
      NR1. An en passant observation concerned high levels of NR2C mRNA in the pineal
      gland.

PMID- 8254359
TI  - Postsynaptic calcium, but not cumulative depolarization, is necessary for the
      induction of associative plasticity in Hermissenda.
AB  - The neuronal modifications that underlie associative memory in Hermissenda have
      their origins in a synaptic interaction between the visual and vestibular
      systems, and can be mimicked by contiguous in vitro stimulation of these
      converging pathways. At the offset of vestibular stimulation (i.e., hair cell
      activity), the B photoreceptors are briefly released from synaptic inhibition
      resulting in a slight depolarization (2-4 mV). If contiguous pairings of light
      induced depolarization and presynaptic vestibular activity occur in close
      temporal succession, this depolarization "accumulates" and has been hypothesized
      to culminate in a sustained rise in intracellular Ca2+ and a resultant Ca(2+)
      mediated phosphorylation of K+ channels as well as an associated increase in
      input resistance. Here we demonstrate that this cumulative depolarization is
      neither necessary nor sufficient for the biophysical modifications of the B cell
      membrane indicative of memory formation. Consistent with several recent reports
      of one-trial learning in Hermissenda, one pairing of light with mechanical
      stimulation of the vestibular hair cells resulted in a rise in neuronal input
      resistance across the B cell membrane that was attenuated by a prepairing
      iontophoretic injection of the Ca2+ chelator EGTA (25 mM), indicating that this
      potentiation was Ca2+ dependent. However, the use of a single pairing negates the
      possibility of an accumulation of depolarization across trials. In a subsequent
      experiment, B photoreceptors underwent a cumulative depolarization, and a
      coincident rise in input resistance, during multiple pairings of light and hair
      cell stimulation. However, if the B photoreceptor was voltage clamped at its
      initial resting potential before and after each pairing, thus eliminating the
      cumulative depolarization, the rise in resistance not only persisted, but was
      enhanced. Moreover, if unpaired light presentations were followed by a current
      induced depolarization (to mimic cumulative depolarization), no increase in input
      resistance was detected. To assess directly the effect of a cumulative
      depolarization on the voltage-dependent Ca2+ current, an analysis of the inward
      current on the B cell soma membrane was conducted. It was determined that (1) the
      inward current may undergo a partial inactivation during sustained
      depolarization, (2) the peak current was depressed during repetitive
      depolarizations, and (3) the peak current underwent a steady-state inactivation,
      such that it was reduced when elicited from holding potentials more positive than
      -60 mV. The analysis of this current suggests that pairings of light and
      presynaptic activity would reduce voltage-dependent Ca2+ influx when those
      pairings are conducted at depolarized membrane potentials, such as during
      cumulative depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254360
TI  - Increase of tryptophan hydroxylase enzyme protein by dexamethasone in
      adrenalectomized rat midbrain.
AB  - Using two specific anti-peptide antibodies (WH-66 and WH-412) against tryptophan
      hydroxylase (TPH or WH), a single principle band from the midbrain raphe area was
      seen (approximately 49 kDa) in immunoblots. Densitometric comparison of the
      immunoreactivity of the 49 kDa band was greater (50-75%) in immunoblots of
      midbrain raphe samples from adrenalectomized (ADX) rats given dexamethasone (DEX)
      in their drinking water (10 mg/liter) for 12-96 hr. No difference from ADX brains
      was seen in the 49 kDa band after only 4 hr of exposure to DEX in the drinking
      water. Immunocytochemical staining with WH-66 of sections from rat brainstem
      showed specific cellular staining in all of the serotonergic raphe nuclei but not
      in substantia nigra or locus coeruleus. More cellular staining of WH-66
      immunoreactive (WH-66-IR) cells was observed in the dorsal and median raphe
      nuclei in ADX rats given DEX for 72 hr, especially in the perikarya and in the
      primary dendrites. Quantification of staining per cell soma with an automatic
      image analyzer indicates that amount of WH-66-IR in neurons from both the lateral
      wing subdivision of the dorsal raphe nucleus and in the supralemniscal nucleus, B
      9, was 80% higher in the ADX+DEX compared to ADX animals. Interestingly,
      morphometric analysis of these same cells showed a corresponding increase of 37
      80% in somal area. It is suggested that a part of the increase in TPH/WH staining
      may be a consequence of cellular hypertrophy due to DEX treatment of the ADX
      rats.

PMID- 8254361
TI  - Intragenic sequences are required for cell type-specific and injury-induced
      expression of the rat peripherin gene.
AB  - Peripherin is a 57 kDa type III intermediate-filament protein that is thought to
      play a role in axonogenesis both during development and following nerve injury
      (Oblinger et al., 1989; Escurat et al., 1990; Gorham et al., 1990; Troy et al.,
      1990b). We have used transgenic mouse technology to define peripherin gene
      sequences that are necessary for cell type-specific expression and for the
      increase in peripherin that occurs in response to axonal injury. Correct temporal
      and nervous system-specific expression resulted when 5.8 kilobases of peripherin
      5' flanking sequence were linked to a reporter gene, but precise cell type
      specific expression was achieved only when intragenic sequences were included.
      When intragenic sequences were present, peripherin transgenes were expressed in
      dorsal root ganglion neurons and spinal cord motor neurons and were upregulated
      in these cells following nerve injury.

PMID- 8254362
TI  - Differential expression of hyperpolarization-activated currents reveals distinct
      classes of visual cortical projection neurons.
AB  - Combining in vivo retrograde labeling and in vitro electrophysiological recording
      techniques, we examined the distributions, densities, and biophysical properties
      of hyperpolarization-activated inward currents in two types of isolated,
      identified visual cortical projection neurons, superior colliculus-projecting
      (SCP) and callosal-projecting (CP) cells. In SCP cells, two kinetically distinct
      time-dependent hyperpolarization-activated inward current components are present.
      We have termed these Ih,f and Ih,s to denote the fast and slow components,
      respectively, of Ih activation. In CP cells, in contrast, Ih,f and Ih,s are
      differentially expressed. In 59% of the CP cells examined, for example, both Ih,f
      and Ih,s were present. The properties of the currents are indistinguishable from
      those recorded from SCP cells, although both Ih,f and Ih,s are expressed at
      significantly lower densities in this subset of CP cells (as compared to the
      current densities in SCP cells). Of the remaining 41% of the CP cells studied,
      26% were found to express only Ih,s, and 12% of the cells expressed neither Ih,f
      nor Ih,s. Taken together, these results reveal that the electrical properties of
      CP visual cortical neurons are considerably more heterogeneous than those of SCP
      cells. The differential expression of Ih,f and Ih,s is expected to influence the
      integrated responses of different types of cortical projection neurons to
      excitatory and inhibitory synaptic inputs.

PMID- 8254363
TI  - A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for
      functional activation in stress-related neuroendocrine circuitry.
AB  - The promoter regions of the rat corticotropin-releasing factor (CRF), oxytocin
      (OT), and vasopressin (AVP) genes contain sequences similar to the cis-acting
      response element identified for NGFI-B, an immediate-early gene structurally
      related to the steroid hormone receptor superfamily. Combined immuno- and
      hybridization histochemical approaches were used to determine whether challenges
      that influence the synthesis and secretion of CRF, OT, and/or AVP result in
      altered expression in neurosecretory neurons of NGFI-B and another immediate
      early gene, c-fos, which is widely used as a marker for functionally activated
      neurons. NGFI-B mRNA was found to be expressed at constitutively high levels in
      the telencephalon, but not in the endocrine hypothalamus, of unperturbed
      controls; basal levels of c-fos expression were uniformly low throughout the CNS.
      NGFI-B and c-fos mRNAs, and Fos protein, were induced with a similar time course
      and in similar neuroendocrine cell types in response to acute hypotensive
      hemorrhage (15% reduction in blood volume), intravenous injection of interleukin
      1 beta (IL-1 beta; 1.87 micrograms/kg), chronic salt loading (7 d maintenance on
      2% saline), and acute bilateral adrenalectomy. c-fos mRNA and Fos protein were
      readily demonstrable in afferent pathways that have been implicated as mediating
      the neuroendocrine responses in the three stress paradigms; these include
      medullary catecholaminergic cell groups in response to IL-1 beta and hemorrhage,
      and cell groups lining the lamina terminalis in response to salt loading.
      Challenge-specific induction of NGFI-B expression was detectable in these
      extrahypothalamic cell groups, though with a lesser sensitivity than that
      required to reveal NGFI-B induction in the hypothalamus, or c-fos expression in
      these related afferents. These results establish NGFI-B as a useful adjunct to c
      fos, for revealing synaptic and/or transcriptional activation in the magno- and
      parvocellular neurosecretory systems. Differences in the sensitivity of the two
      markers in revealing functionally related activation in extrahypothalamic regions
      speak to general issues concerning the use of immediate-early genes in mapping
      functional circuitry in the CNS.

PMID- 8254364
TI  - FMRFamide produces biphasic modulation of the LFS motor neurons in the neural
      circuit of the siphon withdrawal reflex of Aplysia by activating Na+ and K+
      currents.
AB  - The molluscan neuropeptide FMRFamide has an inhibitory effect on transmitter
      release from the presynaptic sensory neurons in the neural circuit for the siphon
      withdrawal reflex. We have explored whether FMRFamide also acts postsynaptically
      in motor neurons in this circuit, focusing on the LFS motor neurons. FMRFamide
      typically produces a biphasic response in LFS neurons: a fast excitatory response
      followed by a prolonged inhibitory response. We have analyzed these postsynaptic
      actions and compared them with the mechanism of FMRFamide's inhibition of the
      presynaptic sensory neurons. The transient excitatory effect of FMRFamide, which
      desensitizes rapidly, is due to activation of a TTX-insensitive, Na(+)-dependent
      inward current. The late hyperpolarizing phase of the FMRFamide response results
      from activation of at least two K+ currents. One component of the hyperpolarizing
      response is active at rest and at more hyperpolarized membrane potentials, and is
      blocked by 5 mM 4-aminopyridine, suggesting that it differs from the previously
      described FMRFamide-modulated K+ currents in the presynaptic sensory neurons. In
      addition, FMRFamide increases a 4-aminopyridine-insensitive K+ current.
      Presynaptically, FMRFamide increases K+ conductance, acting via release of
      arachidonic acid. In the LFS motor neurons, application of arachidonic acid
      mimicked the prolonged, hyperpolarizing phase of the FMRFamide response; 4
      bromophenacyl bromide, an inhibitor of phospholipase A2, selectively blocked this
      component of the FMRFamide response. Thus, FMRFamide may act in parallel pre- and
      post-synaptically to inhibit the output of the siphon withdrawal reflex circuit,
      producing this inhibitory effect via the same second messenger in the sensory
      neurons and motor neurons, though a number of the K+ currents modulated in these
      two types of neurons are different.

PMID- 8254365
TI  - Single channel characterization of multiple types of potassium channels in
      demyelinated Xenopus axons.
AB  - Single channel currents in internodes of demyelinated Xenopus axons were measured
      with the gigaseal patch-clamp technique. Demyelination induced by injected
      lysolecithin allows the entire internodal axolemma to be accessible to a patch
      electrode. Four classes of K+ channels in this region were characterized. A
      Ca(2+)-activated K+ channel [K(Ca)] with a single channel conductance of 235 pS
      was found. In the presence of 10(-3), 10(-4), 10(-5), and 10(-6) M intracellular
      free [Ca2+]i, the half-activation voltages are -24.1, -20.8, 30.2, and 111 mV,
      and the voltage sensitivities are 18.3, 17.2, 23.7, and 21 mV per e-fold change
      in open probability, respectively. The half-activation Ca2+ concentration at 40
      mV is 10(-5) M and the Hill coefficient of Ca2+ binding is 1.7. The K(Ca)
      channels were sometimes found in clusters, three to six channels in a patch. A
      125 pS ATP-sensitive K+ channel was inhibited by the internal application of 2 mM
      ATP. Its activation was voltage independent. This channel may be important in the
      regulation of resting potential. A background K+ channel exhibited outwardly
      rectifying unitary current (176 pS) in symmetrical 115 mM KCl solutions but the
      ensemble-averaged I-V curve was ohmic. The voltage dependence is very weak, 220
      mV per e-fold change in open probability. The nearly symmetrical macroscopic I-V
      curve of the background channel suggests a role in maintaining the axonal resting
      potential. A 28 pS delayed-rectifier K+ channel is found to be blocked internally
      by 2 mM 4-aminopyridine and by 10 mM tetraethylammonium. The half-activation
      voltage is -41 mV and the voltage sensitivity is 8 mV per e-fold change in open
      probability.

PMID- 8254366
TI  - Cloning and differentiation-induced expression of a murine serotonin1A receptor
      in a septal cell line.
AB  - A neuronal cell model endogenously expressing the 5-HT1A receptor, in which to
      study the function and regulation of this gene, has yet to be identified. We
      examined murine SN-48 cells, a septum x neuroblastoma fusion cell line that
      proliferates in a nondifferentiated state but can be induced to differentiate
      into neurofilament-positive cells following 24-96 hr treatment with 10 microM
      retinoic acid in low serum. Northern blot analysis demonstrated the presence of a
      single 10.9 kilobase (kb) 5-HT1A receptor RNA species in differentiated SN-48
      cells, which was not detected in undifferentiated SN-48 cells. The presence of
      receptor RNA in differentiated SN-48 cells correlated with the appearance of
      functional responses (i.e., pertussis toxin-sensitive inhibition of cAMP
      accumulation) to 5-HT1A agonists in differentiated but not in undifferentiated
      cells. In order to verify that the large 10.9 kb RNA species in SN-48 cells truly
      corresponded to the mouse 5-HT1A receptor RNA, a cDNA fragment from
      differentiated SN-48 cells was used to clone the corresponding mouse brain cDNA.
      The 2.4 kb cDNA contained a single open reading frame that displayed high (> 85%
      predicted amino acid identity) homology to the human and rat 5-HT1A receptor
      genes. When transfected into receptor-negative Ltk- cells, this cDNA was found to
      direct expression of a murine 5-HT1A receptor. Thus, we conclude that upon
      differentiation SN-48 cells express RNA encoding functional 5-HT1A receptors. The
      SN-48 septal cells will provide a useful cellular model system for investigating
      aspects of neuronal differentiation leading to the development of sensitivity to
      serotonergic input.

PMID- 8254367
TI  - GABA shapes a topographic organization of response latency in the mustache bat's
      inferior colliculus.
AB  - Many neurons in the auditory forebrain of the mustache bat act as coincidence
      detectors for signals separated in time by up to 20 msec. Differences in path
      lengths cannot adequately explain how the nervous system delays one signal
      relative to the other to such a large degree. Several researchers have proposed
      that an inhibitory mechanism might account for long delays, but it has not been
      known where these delays are created. Previous studies, using a variety of
      mammals, have reported that the inferior colliculus contains some cells with much
      longer latencies than those of cells in lower auditory centers, suggesting that
      the inferior colliculus might be the site where long delays are generated. We
      characterized the latencies of cells in the 60 kHz contour of the mustache bat
      inferior colliculus and examined how GABAergic inhibition affected the latencies
      of those cells. Evaluations of the influence of GABA were made by documenting
      changes in response latency that occurred when GABAergic inputs were reversibly
      blocked by iontophoretic application of the GABAA antagonist bicuculline. Prior
      to bicuculline application, latencies varied over a wide range among the
      population of cells and we observed a pattern of latency changes with
      dorsoventral location. The pattern was that the population of neurons in the
      dorsal regions of the inferior colliculus had a wide range of latencies while the
      population in more ventral regions had progressively narrower latency ranges.
      Thus, while some cells at each depth had comparably short latencies, the average
      latency of the population at a given depth was long in the dorsal inferior
      colliculus and became progressively shorter ventrally. The same characteristic
      distribution of latencies and pattern of latency changes with depth were observed
      for cells that had different aural preferences, different rate-intensity
      functions, and different discharge patterns, suggesting that latency is an
      important organizational feature of the inferior colliculus. Bicuculline
      substantially shortened latency in about half of the cells studied, and it
      dramatically altered the pattern of latency changes with depth. These results
      suggest that GABA normally lengthens response latencies and creates a
      dorsoventral grading of delays in the inferior colliculus. This wide range of
      latencies could provide the large latency differences necessary for the
      coincidence detectors in the medial geniculate body tuned to signals separated by
      up to 20 msec.

PMID- 8254368
TI  - cAMP-activated Na+ current of molluscan neurons is resistant to kinase inhibitors
      and is gated by cAMP in the isolated patch.
AB  - The cAMP-dependent Na+ current (INa,cAMP) modulates excitability in many
      molluscan neurons. Rapid activation of INa,cAMP by cyclic nucleotide, its ion
      dependence, and its blockade by divalent cations resemble cyclic nucleotide
      activated cation currents in vertebrate photoreceptors and olfactory receptors,
      where activation has been found to be independent of kinase activity. We tested
      the phosphorylation dependence of INa,cAMP in neurons of the feeding and
      locomotory networks of the predatory marine snail Pleurobranchaea. Identified
      neurons of pedal and buccal ganglia were axotomized for recording the INa,cAMP
      response to iontophoretic injection of cAMP under two-electrode voltage clamp.
      Intracellular injections of specific peptide inhibitor of protein kinase A had no
      blocking effects on activation of INa,cAMP by iontophoretic injection of cAMP.
      Inward single-channel currents were activated in excised inside-out patches
      during exposure to cAMP in salines without added ATP. Sodium was the major
      current carrying ion. Two distinct types of INa,cAMP channel activity were
      observed, where opening probability and open times differed, but conductance was
      similar, 36.7 pS. These observations suggest that INa,cAMP activation occurs by
      direct binding of cAMP to a regulatory site at the channel, rather than by
      phosphorylation.

PMID- 8254369
TI  - Step-tracking movements of the wrist. III. Influence of changes in load on
      patterns of muscle activity.
AB  - Human subjects performed step-tracking movements of the wrist in the radial
      direction. Movement amplitude, external load, and accuracy instructions were
      varied. We used surface electrodes to record muscle activity from an agonist,
      extensor carpi radialis longus, and an antagonist, extensor carpi ulnaris. When
      subjects performed movements "as fast as possible" that were opposed by different
      external loads, we observed two distinct patterns of modulation of the agonist
      burst. In one pattern, termed pulse-height modulation, the force of the agonist
      muscle was graded by varying the peak amplitude of a short-duration agonist
      burst. This pattern occurred when subjects performed movements of different
      amplitudes with a lightweight manipulandum. In the other pattern, termed pulse
      width modulation, the force of the agonist muscle was graded by varying the
      duration of an agonist burst of nearly maximal amplitude. When the agonist burst
      was prolonged, the onset of antagonist activity was delayed. This pattern
      occurred when subjects performed movements of different amplitudes that were
      opposed by elastic or viscoelastic loads applied to a heavy manipulandum. The
      strongest subject exhibited more pulse-height modulation and less pulse-width
      modulation of the agonist burst than other subjects. Conversely, the weakest
      subject displayed more pulse-width modulation of the agonist burst than other
      subjects. These observations indicate that the force requirements of a task,
      relative to the force generating capacity of a subject's agonist muscle(s), have
      a significant influence on the pattern of agonist modulation. In a second
      experiment using three nonhuman primates, we observed that agonist bursts in
      wrist flexor and extensor muscles exhibited strikingly different patterns of
      modulation. For wrist flexion, agonist bursts in wrist flexors were brief and
      displayed pulse-height modulation when movement amplitude was varied. For wrist
      extension, agonist bursts in wrist extensors were prolonged and displayed largely
      pulse-width modulation when movement amplitude was varied. We suggest that the
      distinct patterns of modulation observed in the wrist muscles of monkeys were due
      to differences in the strength of wrist flexors and extensors, rather than to
      alterations in movement strategy. In a third experiment, we instructed human
      subjects to be "accurate" when they made step-tracking movements. When subjects
      performed movements with a lightweight manipulandum, most displayed short
      duration agonist bursts that were pulse-height modulated. When subjects performed
      "accurate" movements that were opposed by elastic loads, they displayed pulse
      width modulation of a small-amplitude agonist burst.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8254370
TI  - Long-term potentiation and long-term depression of primary afferent
      neurotransmission in the rat spinal cord.
AB  - Synaptic transmission between dorsal root afferents and neurons in the
      superficial laminae of the spinal dorsal horn (laminae I-III) was examined by
      intracellular recording in a transverse slice preparation of rat spinal cord.
      Brief high-frequency electrical stimulation (300 pulses at 100 Hz) of primary
      afferent fibers produced a long-term potentiation (LTP) or a long-term depression
      (LTD) of fast (monosynaptic and polysynaptic) EPSPs in a high proportion of
      dorsal horn neurons. Both the AMPA and the NMDA receptor-mediated components of
      synaptic transmission at the primary afferent synapses with neurons in the dorsal
      horn can exhibit LTP and LTD of the synaptic responses. In normal and neonatally
      capsaicin-treated rats, the induction of LTP requires the activation of NMDA
      receptor-gated conductances. The induction of LTP or LTD, however, was not
      abolished in the presence of bicuculline, a GABAA receptor antagonist. The
      results demonstrate that distinct and long-lasting modulation in synaptic
      efficiency can be induced at primary afferent synapses with neurons in the
      superficial laminae of spinal dorsal horn by high-frequency stimulation of dorsal
      root afferents and that these changes may be physiologically relevant for
      transmission and integration of sensory information, including pain.

PMID- 8254371
TI  - PKA-dependent regulation of mKv1.1, a mouse Shaker-like potassium channel gene,
      when stably expressed in CHO cells.
AB  - Potassium (K) channels are important regulators of cellular physiology and can
      themselves be modulated by phosphorylation. We have investigated the potential
      protein kinase A (PKA) regulation of mKv1.1, a mouse Shaker-like K channel gene,
      when it is expressed in stably transfected Chinese hamster ovary (CHO) cell
      lines. Whole-cell patch-clamp records show that expression of mKv1.1 gives rise
      to a rapidly activating, sustained K+ current, referred to classically as a
      delayed rectifier-type current. In order to study the effects of PKA, we compared
      cell lines transfected with mKv1.1 alone with lines cotransfected with both
      mKv1.1 and a plasmid encoding a dominant negative mutation in the regulatory
      subunit of PKA. These mutant regulatory subunits bind to endogenous catalytic
      subunits of PKA but do not respond to cAMP, thereby causing a chronic reduction
      in the basal PKA activity in these cells. We found that mKv1.1 current kinetics
      are unaltered but current density is 3.4-fold higher in the cell lines expressing
      mutant regulatory subunit than in lines expressing only mKv1.1. RNase protection
      assays indicate that levels of the specific RNA for mKv1.1 are increased almost
      twofold in the lines expressing mutant regulatory subunit over the lines
      expressing mKv1.1 only. Further, the levels of mKv1.1 protein, assayed using an
      mKv1.1 channel-specific antibody, are increased by almost a factor of 3 between
      the two types of cell lines. These results suggest that PKA can regulate mKv1.1
      channel expression by changing steady-state levels of RNA and by other
      posttranscriptional mechanisms.

PMID- 8254372
TI  - Development of orientation selectivity in ferret visual cortex and effects of
      deprivation.
AB  - The orientation selectivity of cells in ferret primary visual cortex was studied
      during normal development and in animals deprived of vision or of visual cortical
      activity. In normal animals from the age when visual responses were first
      recorded (postnatal day 23) through postnatal week 5, only about 25% of cells
      showed orientation-selective responses. By postnatal week 7, cortical responses
      had matured to an adult-like state, with approximately 75% of cells clearly
      selective for orientation. This development of orientation selectivity was not
      merely a reflection of the development of cortical cell responsiveness: at all
      ages studied, there was no correlation between responsiveness and selectivity.
      Infusion of TTX into visual cortex to silence neuronal activity completely
      blocked the maturation of orientation selectivity. Visual deprivation by
      bilateral lid suture impaired but did not completely block the normal development
      of orientation selectivity. We conclude that the maturation of orientation
      selective responses in ferret primary visual cortex requires cortical neuronal
      activity, and that normal development requires visually driven activity.

PMID- 8254373
TI  - Atrophy but not death of adult septal cholinergic neurons after ablation of
      target capacity to produce mRNAs for NGF, BDNF, and NT3.
AB  - The effect of unilateral excitotoxic ablation of hippocampal neurons was
      investigated on (1) the local production of mRNA for NGF and related
      neurotrophins, (2) the amount of NGF protein in the septal region, and (3) the
      viability and appearance of afferent septal cholinergic neurons in adult rats.
      After near complete ablation of hippocampal neurons, total levels of NGF, brain
      derived neurotrophic factor (BDNF), and neurotrophin-3 (NT3) mRNA measured by
      quantitative Northern blot analysis in the hippocampal remnant fell
      significantly, to less than 25% of control values by 28 d and to less than 9% by
      300 d. In the septal region ipsilateral to such lesions, NGF protein levels
      measured by ELISA fell significantly, to about 35% of control values, but the
      number of immunohistochemically detected cholinergic neurons did not decline
      significantly for up to 500 d. Instead, the cholinergic neurons persisted in an
      atrophied state, exhibiting severe shrinkage and reduced staining for the
      transmitter-synthesizing enzyme ChAT. The parameters of cell size and ChAT
      staining intensity correlated significantly with the amount of hippocampal tissue
      present. These findings indicate that in adult rats, target-derived NGF, BDNF,
      and NT3 do not regulate the survival of septal cholinergic neurons in proportion
      to the number of target neurons present. Moreover, the findings suggest that one
      or more of these target-derived neurotrophins regulate the structural and
      chemical phenotype of these neurons in the adult.

PMID- 8254374
TI  - Developmental changes produced in the retinofugal pathways of rats and ferrets by
      early monocular enucleations: the effects of age and the differences between
      normal and albino animals.
AB  - Early monocular enucleations were done in rats, either at embryonic day 16 (E16)
      or on the day of birth, and the surviving uncrossed pathway was studied either at
      birth for some of the animals enucleated prenatally, or in the adult for all of
      the other animals. The uncrossed pathways were studied by using HRP as a
      retrograde tracer. The neonatal enucleations showed the increase of the surviving
      uncrossed component previously documented by others. In contrast to this, a
      prenatal enucleation produced a significant reduction in the surviving uncrossed
      pathway at birth. If these animals survived to be adults, then the surviving
      uncrossed pathway was slightly increased relative to normal. We conclude that two
      quite distinct mechanisms have been exposed by these experiments, one acting
      prenatally and producing a reduction in the uncrossed pathway, and the other
      acting postnatally and producing an increase. The postnatal effect, which is due
      to a decrease of the normally occurring ganglion cell death, thus neutralizes the
      prenatal effect, so that the most effective demonstration of the prenatal effect
      is to be seen before the period of cell death (early postnatal in rats and
      ferrets). The same methods were applied to prenatal ferrets at E26-E28 and, in
      order to see the maximum prenatal effects, the uncrossed pathways were studied at
      birth in all of these animals. There was a severe reduction of the uncrossed
      pathway throughout, and this was greatest in the animals with the earliest
      enucleations. Since the uncrossed pathway in normally reared albino animals is
      abnormally small, the effects of an early prenatal enucleation in albino rats and
      ferrets were compared with the effects in normally pigmented animals in order to
      determine whether the early enucleation was producing an abnormality comparable
      to the albino abnormality. Prenatal enucleations reduced the uncrossed pathway
      not only in normally pigmented but also in albino neonatal rats and ferrets.
      Further, the characteristic position of the nasal border of the temporal retina,
      which is abnormal in albino animals, was unaffected by the enucleation in either
      the albino or the pigmented animals, except where, in ferrets, enucleations
      produced a complete loss of the temporal concentration of ipsilaterally
      projecting ganglion cells (the temporal crescent). The earlier enucleations
      showed a greater tendency to produce such a complete loss of the temporal
      crescent. We conclude that the developmental mechanisms affected by the early
      enucleations are distinct from those that act to produce the albino abnormality
      even though both produce an abnormally small uncrossed pathway.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8254375
TI  - Marked increase in beta-tubulin mRNA expression during regeneration of axotomized
      retinal ganglion cells in adult mammals.
AB  - Changes in gene expression were investigated in axotomized CNS neurons under
      conditions that inhibit or permit regrowth of their damaged axons. Levels of mRNA
      encoding beta-tubulin, the 150 kDa neurofilament subunit (NF-M), and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were examined by quantitative in
      situ hybridization of adult rat retinal ganglion cells (RGCs) after axotomy in
      the optic nerve or during regeneration in a peripheral nerve (PN) graft. Soon
      after optic nerve section beta-tubulin, NF-M, and GAPDH mRNA levels decreased and
      remained low during the 1 month studied. In these retinas beta-tubulin mRNA fell
      to approximately 50% of normal controls. However, in the PN-grafted retinas,
      where approximately 20% of the surviving axotomized RGCs regenerate their axons,
      there were "hot spots" of beta-tubulin mRNAs where neuronal levels were nearly
      300% higher than in controls. By retrograde neuronal labeling these hot spots
      were shown to correspond to the injured RGCs that regrew their axons into the PN
      graft; beta-tubulin mRNA levels in nonregenerating RGCs of the same retinas
      averaged 63% of controls. We suggest that interactions of RBC axons and
      components of the grafts' non-neuronal environment play a key role in the over
      fourfold differences in beta-tubulin mRNA levels observed between injured and
      regenerating RGCs.

PMID- 8254376
TI  - Apical dendrites of the neocortex: correlation between sodium- and calcium
      dependent spiking and pyramidal cell morphology.
AB  - Apical dendrites and somata of layer V pyramidal neurons were recorded with tight
      seal patch electrodes in a slice preparation of rat somatosensory cortex.
      Recording sites were confirmed by measurements of the electrode location and by
      staining with biocytin. Dendritic recordings were made along the main trunk of
      the apical dendrite, usually within layer IV, at distances from 100 to 500
      microns from the soma. Most cells recorded through the dendrite had a distinct
      enlargement of the apical trunk around the presumed recording site. The
      electrical properties of apical dendrites were readily distinguishable from those
      of somata. Dendrites generated two types of response when injected with
      depolarizing current. Group I responses were relatively small and broad Na(+)
      dependent action potentials whose amplitude and rate-of-rise were negatively
      correlated with recording distance from the soma. Group II responses were
      complex, clustered firing patterns of Na(+)-dependent spikes together with higher
      threshold slow spikes or plateaus; in these dendrites spike parameters were not
      correlated with distance from the soma. These two response groups were correlated
      with dendritic morphology: group I had significantly fewer oblique branches on
      the apical dendrite (5.5 vs 12.0) and a thinner apical trunk (2.0 vs 2.5 microns)
      than group II. TTX (1-2 microM) selectively blocked fast dendritic spikes, but
      not slow spikes and plateaus. Blocking Ca2+ currents reduced complex firing
      patterns and suppressed high-threshold slow spikes. Physiological and
      pharmacological studies imply that slow spikes and plateau potentials were
      primarily generated by high-threshold Ca2+ channels in the apical dendrite.
      Stimulating axons of layer I elicited EPSPs on distal apical dendrites of layer V
      cells. Recordings from both groups of apical dendrites revealed that EPSPs
      triggered a variety of distally generated, all-or-nothing depolarizations. The
      results show that voltage-dependent Na+ and Ca2+ currents are present in distal
      apical dendrites, in variable densities. These currents significantly modify
      distal synaptic events. The prevalence and character of active dendritic spiking
      (and presumably of Na+ and Ca2+ channel densities) correlate with the morphology
      of the apical dendritic tree.

PMID- 8254377
TI  - Ionic flux contributions to neocortical slow waves and nucleus basalis-mediated
      activation: whole-cell recordings in vivo.
AB  - Slow, rhythmic membrane potential (Vm) fluctuations occur spontaneously in
      cortical neurons of urethane-anesthetized rats, and likely underlie EEG activity
      in the same low-frequency (1-4 Hz or delta) range. Nucleus basalis (NB)
      stimulation elicits neocortical activation, simultaneously modifying Vm and EEG
      fluctuations, by way of cortical muscarinic ACh receptors (Metherate et al.,
      1992). To investigate the nature of spontaneous fluctuations and their
      modification by NB stimulation, we have obtained intracellular recordings from
      auditory cortex using the whole-cell recording technique in vivo. Spontaneous Vm
      fluctuations appeared to contain three components whose polarity and time course
      resembled the EPSP, putative Cl(-)-mediated IPSP, and putative K(+)-mediated,
      long-lasting IPSP elicited by thalamic stimulation. The spontaneous, long-lasting
      hyperpolarization, whose rhythmic occurrence appeared to set the slow-wave
      rhythm, was associated with an increased conductance that could shunt the
      thalamocortical EPSP. We hypothesized that spontaneous Vm fluctuations arise from
      intermixed rapid depolarizations, rapid Cl(-)-mediated hyperpolarizations, and
      long-lasting, K(+)-mediated hyperpolarizations. NB-mediated cortical activation
      might then result from muscarinic suppression of K+ permeability, allowing the
      rapid depolarizations and Cl- fluxes to continue uninterrupted. Tests of this
      hypothesis showed that (1) intracellular blockade of K+ channels by rapid
      diffusion of Cs+ from the recording pipette resulted in suppression of
      spontaneous, long-lasting hyperpolarizations, mimicking the effect of NB
      stimulation, and reducing shunting of the thalamocortical EPSP; (2) effects of
      Cs+ and NB stimulation suggested overlapping, or converging, mechanisms of
      action; however, there were important differential effects on the spontaneous,
      long-lasting hyperpolarizations and the K(+)-mediated IPSP; and (3) modifying Cl-
      fluxes with intracellular picrotoxin or high intracellular Cl- concentrations
      resulted in spontaneous and NB-elicited large-amplitude depolarizations. We
      conclude that spontaneous, long-lasting hyperpolarizations are K+ fluxes, but are
      not "spontaneous" K(+)-mediated IPSPs. Since NB-mediated reduction of spontaneous
      hyperpolarizations implies muscarinic suppression of a K+ conductance, the
      spontaneous hyperpolarizations more likely result from the calcium-activated K+
      current, IK(Ca). Finally, Cl- fluxes form an important component of activated Vm
      fluctuations that acts to restrain excessive depolarization.

PMID- 8254378
TI  - The mosaic of midget ganglion cells in the human retina.
AB  - To study their detailed morphology, ganglion cells of the human retina were
      stained by intracellular tracer injection, in an in vitro, whole-mount
      preparation. This report focuses on the dendritic morphology and mosaic
      organization of the major, presumed color-opponent, ganglion cell class, the
      midget cells. Midget cells in the central retina were recognized by their
      extremely small dendritic trees, approximately 5-10 microns in diameter. Between
      2 and 6 mm eccentricity, midget cells showed a steep, 10-fold increase in
      dendritic field size, followed by a more shallow, three- to fourfold increase in
      the retinal periphery, attaining a maximum diameter of approximately 225 microns.
      Despite large local variation in dendritic field size, midget cells formed one
      morphologically distinctive class at all retinal eccentricities. Two midget cell
      types were distinguished by their dendritic stratification in either the inner or
      outer portion of the inner plexiform layer (IPL), and presumably correspond to ON
      and OFF-center cells respectively. The mosaic organization of the midget cells
      was examined by intracellularly filling neighboring cells in small patches of
      retina. For both the inner and outer midget populations, adjacent dendritic trees
      apposed one another but did not overlap, establishing a coverage of no greater
      than 1. The two mosaics differed in spatial scale, however: the outer midget
      cells showed smaller dendritic fields and higher cell density than the inner
      midget cells. An outer:inner cell density ratio of 1.7:1 was found in the retinal
      periphery. An estimate of total midget cell density suggested that the proportion
      of midget cells increases from about 45% of total ganglion cell density in the
      retinal periphery to about 95% in the central retina. Nyquist frequencies
      calculated from midget cell spacing closely match a recent measure of human
      achromatic spatial acuity (Anderson et al., 1991), from approximately 6 degrees
      to 55 degrees eccentricity. Outside the central retina, midget cell dendrites
      arborized in clusters within the overall dendritic field. With increasing
      eccentricity, the dendritic clusters increased in number and remained small
      (approximately 10-20 microns diameter) relative to the size of the dendritic
      field. Because neighboring midget cell dendritic trees do not overlap, the mosaic
      as a whole showed a pattern of clusters and holes. We hypothesize that midget
      cell dendritic trees may contact individual axon terminals of some midget bipolar
      cells and avoid contacting others, providing a basis for the formation of cone
      specific connections in the IPL.

PMID- 8254379
TI  - Seasonal fluctuations in brain nuclei in the red-sided garter snake and their
      hormonal control.
AB  - In many vertebrates, breeding seasons are protracted and mating behavior is
      temporally associated with gonadal growth and increased sex steroid hormone
      secretion. In the red-sided garter snake (Thamnophis sirtalis parietalis), mating
      behavior is restricted to the 2-4 weeks immediately following emergence from
      winter dormancy. During this period mating behavior is sex-specific: chin-rubbing
      is exhibited only by males and receptivity to chin-rubbing is exhibited only by
      females. It is remarkable that mating occurs when the gonads are small and
      circulating concentrations of gonadal hormones are low. As in other vertebrate
      species, limbic nuclei are involved in the mediation of mating behaviors. To
      determine if limbic nuclei are sexually dimorphic and, further, whether they
      fluctuate in size with the seasons, the volume of brain areas was measured in
      both sexes at different times of the year (spring, fall, hibernation) and after
      hormone manipulation (gonadectomy and gonadectomy plus hormone treatment). The
      areas of interest were the preoptic area (POA), ventromedial hypothalamus (VMH),
      and the nucleus sphericus (NS or amygdala); control areas included the external
      nucleus of the optic tract (a cell-rich area) and medial forebrain bundle (a
      fiber-rich area). Comparisons according to season and manipulation revealed only
      two instances of sexual dimorphism: the POA of females was significantly smaller
      than that of males during hibernation and the NS of females was significantly
      smaller than that of males in those animals not subjected to hibernation. This
      general lack of sexual dimorphisms in the brain despite the sex-specificity of
      the behavior patterns and their marked seasonality may reflect the dissociated
      reproductive pattern characteristic of this species.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8254380
TI  - Organized growth of thalamocortical axons from the deep tier of terminations into
      layer IV of developing mouse barrel cortex.
AB  - The thalamocortical projection to rodent somatosensory ("barrell") cortex is
      highly ordered in both the radial and the tangential dimensions. During a brief
      period of postnatal development, thalamocortical axons establish two tiers of
      terminations, in the deep layers and in layer IV, and form whisker-specific
      clusters within layer IV; however, little is known about the cues that guide them
      to their appropriate radial and tangential positions. To gain insight into
      potential mechanisms underlying this process, we studied the development of
      thalamocortical termination patterns in mouse barrel cortex at high spatial
      resolution. Developing thalamocortical axons were labeled in fixed slices with
      the lipophilic carbocyanine dye Dil and imaged with a laser scanning confocal
      microscope. On the day of birth (postnatal day 0, P0) axons coursed through
      layers VI and V, with little or no branching. By P2 the lower tier of
      terminations, at the border of layers VI and V, was clearly identifiable. Below
      this tier axons coursed obliquely or tangentially, forming a dense meshwork of
      intersecting fibers, but with no apparent branching. By P4 the upper tier of
      terminations, in layer IV, was clearly recognizable, and consisted of periodic,
      dense clusters of terminal arborizations. In marked contrast to the oblique and
      apparently disorderly course followed by axons in layer VI and lower layer V,
      axons in upper layer V heading toward the upper tier were organized in loose
      bundles running radially, suggesting that axons destined to terminate in a
      particular layer IV barrel had already reached their appropriate tangential
      coordinates within the lower tier. Thus, the pattern of thalamocortical
      terminations in layer IV seems to be projected from the deep tier of
      terminations, and does not develop from an initially profuse arborization pattern
      through pruning of inappropriate branches.

PMID- 8254381
TI  - Effects of the excitatory amino acid receptor antagonists kynurenate and indole-2
      carboxylic acid on behavioral and neurochemical outcome following experimental
      brain injury.
AB  - The overactivation of the NMDA receptor is thought to be a major contributor to
      the pathophysiologic sequelae of traumatic brain injury (TBI), which commonly
      includes memory dysfunction. Uniquely, potentiation of the NMDA receptor is
      dependent on the binding of glycine to a distinct site on the receptor. Despite
      the potential role of the NMDA receptor in the development of post-TBI cognitive
      deficits, no studies to date have evaluated the efficacy of NMDA receptor
      antagonists on memory dysfunction after brain injury. Moreover, glycine site
      antagonists have not been employed as potential therapeutic agents in models of
      TBI. In the present study, we evaluated the effects of two glycine site
      antagonists, kynurenate (KYNA) and indole-2-carboxylic acid (I2CA), on memory and
      motor dysfunction, cerebral edema formation, and changes in regional total tissue
      brain [Na], [K], [Ca], [Mg], and [Zn], following lateral fluid-percussion brain
      injury in the rat. We found that both KYNA (300 mg/kg) and I2CA (50 mg/kg and 20
      mg/kg) administered 15 min postinjury dramatically attenuated trauma-induced
      cognitive dysfunction (p < 0.01). In addition, both compounds improved neurologic
      motor deficits measured at 2 weeks following injury (p < 0.05). KYNA (300 mg/kg)
      reduced edema in the cortex, hippocampus, and thalamus, while I2CA (20 mg/kg)
      reduced edema formation only in the thalamus. Differential effects of KYNA and
      I2CA on cation concentrations were also noted. KYNA attenuated the postinjury
      increase in regional tissue [Ca]; however, it had little effect on other cation
      concentrations. I2CA reversed the postinjury regional increases in [Na] and
      decreases in [K], [Mg], and [Zn], but had little effect on [Ca] changes. These
      results indicate that KYNA and I2CA may have differential, but beneficial effects
      on both behavioral and neurochemical sequelae of TBI.

PMID- 8254382
TI  - The striopallidal neuron: a main locus for adenosine-dopamine interactions in the
      brain.
AB  - Recent pharmacological data suggest that a receptor-receptor interaction between
      adenosine A2 and dopamine D2 receptors in the brain underlies the behavioral
      effects of adenosine agonists and adenosine antagonists, such as caffeine and
      theophylline. According to this interaction, stimulation of A2 receptors inhibits
      and their blockade potentiates the effects of D2 receptor stimulation.
      Furthermore, both A2 and D2 receptors are selectively colocalized on GABAergic
      striopallidal neurons. In this microdialysis investigation the effect of
      intrastriatal infusion of adenosine and dopamine agonists and antagonists alone
      or in combination was studied on the release of GABA from the terminals of the
      striopallidal neuron in awake, freely moving rats. We report that the GABAergic
      striopallidal neuron, which is a key component of the indirect striatal efferent
      pathway, is a main locus for A2-D2 interactions in the brain and possibly a main
      target for the central actions of adenosine agonists and antagonists.

PMID- 8254383
TI  - Serotonin-deficient mutants and male mating behavior in the nematode
      Caenorhabditis elegans.
AB  - Defining a behavior that requires the function of specific neurons in the free
      living nematode Caenorhabditis elegans can allow one to screen for mutations that
      disrupt the specification or function of those neurons. We identified serotonin
      immunoreactive neurons required for tail curling or "turning" behavior exhibited
      by C. elegans males during mating. Males mutant in three different genes that
      reduce serotonin expression, cat-1, cat-4, and bas-1, exhibited defects in
      turning behavior similar to those of wild-type males in which these neurons were
      ablated. The turning defect of cat-4 males was rescued by exogenous serotonin,
      consistent with the idea that their behavioral defect is caused by a lack of
      serotonin. While the serotonin-deficient mutants we analyzed shared certain
      behavioral traits, they were blocked for serotonin synthesis at different steps.
      Analysis of these and additional serotonin-deficient mutants may help us
      understand how a neuron controls the expression of a serotonergic phenotype.

PMID- 8254384
TI  - Effects on visual recognition of combined and separate ablations of the
      entorhinal and perirhinal cortex in rhesus monkeys.
AB  - Performance on visual delayed nonmatching-to-sample was assessed in rhesus
      monkeys with combined and separate ablations of the perirhinal and entorhinal
      cortex, as well as in unoperated controls. Combined (i.e., rhinal cortex) lesions
      yielded a striking impairment on this task, one almost as severe as that seen
      after combined amygdalohippocampal removals that included some of this subjacent
      cortex (Mishkin, 1978; Murray and Mishkin, 1984). Ablations of the perirhinal
      cortex alone produced a deficit nearly as severe as that found after rhinal
      cortex lesions, whereas ablations of the entorhinal cortex alone produced only a
      mild deficit. Contrary to the conclusion from an earlier study (Murray and
      Mishkin, 1986), the present results demonstrate not only that damage limited to
      the rhinal cortex is sufficient to produce a severe loss in visual recognition,
      but also that such damage leads to a far greater loss than damage to any other
      single structure in the medial part of the temporal lobe.

PMID- 8254385
TI  - California grants Ward Valley license.

PMID- 8254386
TI  - Safety and clinical utility of combined intravenous dipyridamole/symptom-limited
      exercise stress test with thallium-201 imaging in patients with known or
      suspected coronary artery disease.
AB  - Dipyridamole-induced coronary hyperemia with 201Tl myocardial perfusion
      scintigraphy can detect ischemic regions in individuals unable to perform
      adequate exercise, but it has several limitations. Symptom-limited exercise
      supplementation to intravenous dipyridamole can potentially overcome them, but
      the safety and diagnostic accuracy for this combination has not been established.
      Between 1987 and 1991, 441 consecutive patients were assessed for combined
      symptom-limited exercise test preceded by i.v. dipyridamole. Clinical records
      could not be obtained for 37 patients, and 40 patients were not exercised because
      they were unable; therefore 384 patients (mean age 58 +/- 9.8 yr, 278 men)
      underwent symptom-limited exercise preceded by 0.56 mg/kg of dipyridamole and
      followed by planar 201Tl perfusion scintigraphy. Following dipyridamole infusion,
      systolic blood pressure fell by 10 +/- 14 mmHg and heart rate increased by 8 +/-
      11 bpm. Adverse effects were experienced by 77 people (dizziness in 44; headache
      in 11; nausea in 9; syncope in 2 and chest pain in 11). Exercise heart rate was
      69% +/- 16% of predicted maximum and ST shift was -0.9 +/- 0.9 mm. Following
      exercise, seven patients required aminophylline (four after dizziness, two after
      headache, one after chest pain), which was uniformly successful. There were no
      episodes of prolonged chest pain, MI, death or serious arrhythmia. Safety was
      maintained for people with severe triple coronary artery disease, the elderly (>
      70 yr) and those with significant pulmonary disease. Sensitivity was 95% for at
      least one with > 70% luminal stenosis and 94% for at least one with > 40% luminal
      stenosis. Specificity was 28% and 53% respectively. The addition of a symptom
      limited exercise test to i.v. dipyridamole is safe for all groups of patients
      referred for 201Tl study.

PMID- 8254387
TI  - Exercise-dipyridamole myocardial perfusion imaging: the circle is now complete.

PMID- 8254388
TI  - Heart and skeletal muscle glucose disposal in type 2 diabetic patients as
      determined by positron emission tomography.
AB  - Myocardial and skeletal muscle glucose uptake was examined in 9 type 2 diabetic
      patients and 13 control subjects using PET and the insulin clamp technique. All
      subjects had clinically stable coronary heart disease. To simulate the clinical
      situation, diabetic patients were kept slightly hyperglycemic during the clamp
      study. Consequently, there were no differences in skeletal muscle or total body
      glucose disposal between the two groups. With PET, myocardial glucose uptake was
      12-20-fold greater than that in skeletal muscle in both groups. However, in the
      diabetic patients, myocardial glucose uptake was 39% lower (p < 0.05) than in the
      control subjects. These data suggest a defect in myocardial glucose utilization
      in type 2 diabetes and emphasize the need for standardized metabolic conditions
      in diabetic patients during 18FDG PET imaging.

PMID- 8254389
TI  - The value of quantitative analysis of glucose utilization in detection of
      myocardial viability by PET.
AB  - To study whether absolute quantitation of regional myocardial glucose utilization
      (rMGU) enhances detection of myocardial viability, 70 nondiabetic patients with
      prior myocardial infarction and angiographically confirmed coronary artery
      disease were studied with [18F]FDG PET after oral glucose loading. Forty-eight
      patients were also revascularized and underwent echocardiography after
      revascularization to detect wall motion recovery. The rMGU was calculated in
      eight myocardial segments in each patient and the results were compared to
      normalized (relative) [18F]FDG uptake values. In normal segments (n = 225), rMGU
      was 56 +/- 18 mumole/min/100 g (mean +/- s.d.) and relative [18F]FDG uptake 97%
      +/- 12%. The interindividual variation of rMGU in normal myocardium was greater
      than the intraindividual variation (s.d. 31% versus 11%). The respective values
      for relative [18F]FDG uptake were 9% and 10%. Both rMGU and [18F]FDG uptake were
      significantly reduced in segments with scarring observed visually during bypass
      surgery (29 +/- 19 mumole/min/100 g and 45% +/- 22%, n = 26). The rMGU and
      [18F]FDG uptake were higher in segments that recovered after revascularization
      (53 +/- 17 mumole/min/100/g and 110% +/- 21%, n = 27) than in those that did not
      (37 +/- 20 mumole/min/100 g and 65% +/- 24%, n = 63). However, due to larger
      variability of rMGU values, normalized [18F]FDG uptake was superior to rMGU in
      separating normal and scar segments as well as in predicting wall motion
      recovery. We conclude that rMGU variability is notable and is caused mainly by
      variations between patients. Interindividual variation is reduced by
      normalization, which results in more accurate assessment of myocardial viability.
      Thus, static imaging and semiquantitative analysis are sufficient for the
      clinical assessment of myocardial viability.

PMID- 8254390
TI  - Estimation of dopamine D2 receptor binding potential in the striatum with iodine
      123-IBZM SPECT: technical and interobserver variability.
AB  - Factors contributing to the quantification of the striatal dopamine D2 receptor
      binding potential in vivo using 123I-iodobenzamide (123I-IBZM) and SPECT were
      analyzed in phantom studies, healthy volunteers and in patients with the
      parkinsonian syndrome. A cylindrical brain phantom based on a stereotactic brain
      atlas was constructed with independently fillable compartments representing two
      striata (ST), cerebellum (CB) and background. Clinical 123I-IBZM SPECT studies
      were performed on 15 healthy volunteers and on 28 patients with parkinsonian
      syndrome. Interobserver variability of region of interest (ROI) selection and
      count ratios were estimated by two independent observers. ROIs for the striatum
      were either fixed, based on a stereotactic brain atlas, or drawn manually, based
      on 70% isocontour lines. Reference regions were either the cerebellum (isocontour
      ROIs) or the occipital cortex (occiptal cortex; fixed ROIs). The brain phantom
      measurements showed linearity with respect to radioactivity concentration, good
      reproducibility and good contrast recovery. The interobserver study showed that
      the striatum-to-occiptal cortex ratio with fixed ROIs for the striatum, as an
      estimate for striatal D2 receptor binding potential, resulted in a means of
      separating patients with normal receptor activity from those with decreased
      striatal dopamine D2 receptor activity.

PMID- 8254392
TI  - Thallium-201 SPECT in the evaluation of gliomas.

PMID- 8254391
TI  - Clinical evaluation of thallium-201 SPECT in supratentorial gliomas: relationship
      to histologic grade, prognosis and proliferative activities.
AB  - We performed 201Tl SPECT and cell kinetic studies on 28 presurgical patients with
      supratentorial gliomas by administering bromodeoxyuridine (BUdR). All patients
      had surgery and had follow-up for more than 25 mo. In patients with grade IV
      glioma (198.1% +/- 32.8%, n = 10), the 201Tl index, expressed as the count rate
      of the tumor site to the count rate over the contralateral normal region, was
      significantly higher than that in patients with grade III glioma (140.5% +/-
      15.1%, n = 4, p < 0.01) or low-grade glioma (104.1% +/- 22.6%, n = 14, p <
      0.001). A significant correlation was observed between the 201Tl index and BUdR
      positive cells in excised tumor specimens (r = 0.67, p < 0.001). The 201Tl index
      of the 12 patients who died was higher than those who survived (173.2% versus
      122.4%, p < 0.01). These results show the clinical utility of 201Tl brain SPECT
      in imaging supratentorial glioma and that the 201Tl index is representative of
      proliferative activity of the tumor.

PMID- 8254393
TI  - Thallium-201 SPECT for predicting histological types of meningiomas.
AB  - Early and delayed 201Tl SPECT studies were performed on 13 patients with
      intracranial meningiomas, which were classified in three groups according to
      their histological types: meningothelial (n = 7); transitional and fibroblastic
      (n = 3); and malignant types (n = 3). The early uptake indices (UI, ratios of
      average counts/pixel in the lesion to those of the contralateral area on early
      images) were relatively high in all types: meningothelial meningiomas, 5.75 +/-
      2.16 (mean +/- s.d.); transitional and fibroblastic meningiomas, 4.69 +/- 0.54;
      and malignant meningiomas, 7.10 +/- 3.72. There were no statistical differences
      in relation to histological type. The delayed uptake indices were 2.65 +/- 0.89,
      3.37 +/- 1.02, and 5.16 +/- 1.62, respectively. Statistically, the delayed UI of
      meningothelial meningiomas were lower than those of malignant types (p < 0.05).
      The retention indices (RI, ratios of delayed to early UI) were 0.48 +/- 0.08,
      0.79 +/- 0.16, and 0.84 +/- 0.16, respectively. The RI of the meningothelial type
      were also statistically lower than those of the other two groups (p < 0.05).
      There were no statistically significant differences between transitional plus
      fibroblastic types and malignant meningiomas. We conclude that 201Tl exhibits
      early high accumulations in all types of meningiomas, but its retention rates
      probably differ according to histological types, and a high retention index is
      predictive of the malignant potential in a meningioma.

PMID- 8254394
TI  - A complementary role for thallium-201 scintigraphy with mammography in the
      diagnosis of breast cancer.
AB  - Physical examination and mammography are currently the only proven and reliable
      methods of early detection of breast cancer. Although both procedures are highly
      sensitive, their limited specificity often requires surgical biopsy in order to
      differentiate between malignant and benign lesions. The purpose of this
      prospective study is to investigate the diagnostic specificity of thallium
      imaging for breast cancer and to determine its efficacy as a complement to
      mammography. Two groups were studied: Group A: Patients found to have breast
      abnormalities and scheduled for biopsy or surgery and Group B: Patients who were
      suspected to have a recurrence of cancer after mastectomies or lumpectomies. In
      Group A, thallium scans of 32 breasts in 30 patients were performed prior to
      biopsy or surgery, yielding pathological diagnoses of 31 breasts in 29 patients.
      Results for Group A included seven true-positive thallium scans, twenty-two true
      negative scans, two false-negative scans, and one false-positive scan. In Group
      B, seven patients were scanned to evaluate subcutaneous nodules for breast cancer
      following mastectomy or lumpectomy. Results for Group B included five true
      positive scans, one true-negative scan, one false-negative scan and no false
      positive scans. Thallium breast scanning was shown to have high specificity for
      cancer (specificity 96% and sensitivity 80%), suggesting that this technique
      should be evaluated in additional patient studies to determine its role in
      clinical situations.

PMID- 8254395
TI  - Early detection of lymphoma recurrence with gallium-67 scintigraphy.
AB  - Early detection of tumor relapse in lymphoma patients is often a difficult
      diagnostic problem. CT, which detects a mass, often cannot differentiate between
      fibrosis or relapsed tumor. For this reason, we have studied the value of 67Ga
      scintigraphy in the diagnosis of tumor recurrence. The sensitivity of 67Ga
      scintigraphy in the detection of lymphoma recurrence was studied at an average
      interval of 8.7 mo following treatment in 32 patients who developed recurrent
      lymphoma. Its specificity was studied in 36 patients with no recurrence who were
      in continuous clinical remission. At the time of appearance of relapse, the
      sensitivity of whole-body 67Ga imaging was 95% and the specificity 89%. In 12
      events of recurrence in 10 patients, 67Ga scintigraphy was abnormal at sites that
      later proved to be regions of relapse. In these patients, scintigraphy
      demonstrated recurrence an average of 6.8 mo before the appearance of clinical
      symptoms, findings on clinical examination or abnormality on CT or chest x-rays.
      Gallium-67 scintigraphy, which permits screening of the whole body for recurrence
      in a single study, was of particular value in evaluating lymphoma recurrence,
      since 27% of the recurrences were located exclusively in sites different from the
      original sites of disease. Gallium-67 scintigraphy appears to be a sensitive and
      specific test for restaging patients with lymphoma recurrence.

PMID- 8254396
TI  - The hot spot hepatobiliary scan in focal nodular hyperplasia.
AB  - A prospective study was performed on 14 patients with histologically proven focal
      nodular hyperplasia (FNH) using a hepatobiliary scan with trimethylbromoimino
      diacetic acid (TBIDA) and a colloid scan with rhenium sulfur colloids. TBIDA
      uptake was relatively normal in the region of the tumor, but during the clearance
      phase 23/25 of the tumors were detected by a hot spot of radioactivity. Depending
      on the relative contrast achieved between the tumor and normal liver, this hot
      spot appeared early or later, but was always present at 60 min. In three tumors,
      a "doughnut" pattern was observed within the hot spot due to a central defect.
      Hypervascularization was observed during the perfusion phase in 76% of the
      tumoral sites and normal colloid uptake in only 64%. The detectability of FNH
      appears greater with TBIDA (92%) than with CT or MRI (84%). The high prevalence
      of hot spots may be due to careful technological conditions when obtaining
      hepatobiliary scans. Late images, overexposed films, multiple views and
      stimulation of gallbladder excretion increased tumor detectability. The hot spot
      sign may be a useful tool when combined with the results of other imaging
      modalities in the diagnosis of FNH. The peculiar pathology of FNH with fibrosis,
      hyperplastic hepatocytes and cholangiolar proliferation might explain this
      scintigraphic appearance.

PMID- 8254397
TI  - Rhenium-186-labeled chimeric antibody NR-LU-13: pharmacokinetics, biodistribution
      and immunogenicity relative to murine analog NR-LU-10.
AB  - A mouse-human chimeric monoclonal antibody (NR-LU-13), with the same pancarcinoma
      antigen recognition site as a previously studied murine monoclonal antibody (NR
      LU-10), was radiolabeled with 186Re using a bifunctional chelate. Nine patients
      (ages 31-81 yr) with metastatic adenocarcinoma received 186Re NR-LU-13. A single
      intravenous dose of 42 mg NR-LU-13 labeled with 25 mCi/m2 (two patients) or 60
      mCi/m2 (seven patients) was administered. Mean serum disappearance half-time
      values for the chimeric 186Re NR-LU-10). Fifty percent of the radiolabel was
      excreted in the urine by 6 days. Tumor localization was demonstrated by gamma
      camera imaging in seven of nine patients. The percent injected dose per gram in a
      single tumor biopsy specimen was 0.003% at 72 hr postinjection. Absorbed dose to
      bone marrow was 1.5 +/- 0.7 rads/mCi and resulted in reversible myelosuppression
      in five of six evaluable patients who received 60 mCi/m2: median WBC nadir =
      2500/microliters; median platelet nadir = 85,500/microliters. Low grade fever,
      nausea, slight elevations of liver function tests and mild allergic reactions
      were seen in some patients. The chimeric antibody elicited low levels of anti-NR
      LU-13 antibody in six of eight evaluable patients (75%), in contrast to NR-LU-10
      which elicited higher levels of human anti-mouse antibody in all patients. This
      pilot study demonstrates the ability of the chimeric antibody to target tumors
      with reduced (but not absent) immunogenicity and delayed clearance relative to
      the murine antibody.

PMID- 8254398
TI  - Postprandial gastric motility in infants with gastroesophageal reflux and delayed
      gastric emptying.
AB  - Delayed gastric emptying of formula is observed in many infants with
      gastroesophageal reflux but the mechanisms responsible for this observation are
      not defined. Postprandial gastric motility was quantified using a perfused
      catheter placed into the distal stomach of five infants with gastroesophageal
      reflux and delayed gastric emptying of 99mTc-sulfur colloid-labeled formula. Five
      infants with reflux who exhibited normal emptying of formula served as the
      controls. Gastric motility indices were calculated for 60 min following a meal.
      Half the patients in each group were given metoclopramide following a 30-min
      recording period. In both groups, postprandial gastric motility was similar and
      characterized by minimal gastric contractions. Metoclopramide resulted in
      increased amplitude and duration of antral contractions, but no significant
      differences were noted between groups. The findings suggest that minimal delays
      in gastric emptying in infants with gastroesophageal reflux are not associated
      with significant alterations of postprandial gastric motility.

PMID- 8254399
TI  - Evaluation of experimental liver tumors using fluorine-18-2-fluoro-2-deoxy-D
      glucose PET.
AB  - Japanese white rabbits transplanted with VX2 liver tumors are considered to be a
      suitable experimental model for the evaluation of therapeutic modalities.
      However, there has been no adequate method of assessing the changes of tumor
      metabolism during treatment. In the present study, 15 rabbits with VX2 liver
      tumors were examined by PET using 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG). After
      an intravenous injection of 18F-FDG, serial arterial blood sampling was
      performed. One hour after tracer injection, small pieces of normal liver tissue
      and tumor tissue were excised to determine radioactivity. Dynamic PET images were
      obtained in 11 of the tumor-bearing rabbits, and tumor enzyme activities were
      determined in six rabbits. Fluorine-18-FDG uptake by the VX2 liver tumors was 3.5
      +/- 0.9 times higher than that by the normal liver tissue; so good contrast
      between tumor and normal liver tissue was achieved on PET scans. The enzyme
      activity study showed that VX2 tumors had increased levels of hexokinase and
      pyruvate kinase activity, suggesting an increase of glycolysis. We conclude that
      transplanted VX2 liver tumors could be appropriately evaluated by 18F-FDG PET.

PMID- 8254400
TI  - In vivo bioactivity and biodistribution of chemotactic peptide analogs in
      nonhuman primates.
AB  - The dose dependence of the effect of chemotactic peptide on peripheral leukocyte
      levels was measured in normal Rhesus monkeys. A 99mTc-labeled hydrazino
      nicotinamide (HYNIC) derivatized chemotactic peptide analog was used to study
      biodistribution and inflammation imaging in Rhesus monkeys. In normal animals the
      studies demonstrated that chemotactic peptide induced a clear dose-dependent
      reduction in peripheral leukocyte levels. The decrease in leukocyte number
      occurred almost immediately after injection and rapidly returned to baseline.
      Significant effects on differential WBC count, blood pressure, pulse rate or
      respiration rate were not detected. The lowest dose of peptide tested (10 ng/kg)
      had minimal effect on leukocyte level. The HYNIC derivatized peptide was prepared
      in excellent yield and purity, had biological activity similar to the native
      peptide and was readily labeled at specific activity of > 20,000 mCi/mumole. When
      approximately 0.5 mCi (< 2.0 ng/kg) of radiolabeled peptide was injected in
      monkeys with focal sites of mild sterile inflammation, a pattern of
      biodistribution similar to radiolabeled WBCs was observed and reductions in
      leukocyte levels were not detected. At 3 hr after injection, the site of
      inflammation was readily apparent with a target-to-background ratio of
      approximately 3:1. These studies demonstrate that radiolabeled chemotactic
      peptide analogs are effective agents for imaging sites of inflammation in
      monkeys. By radiolabeling at high specific activity, the effect of these reagents
      on peripheral leukocyte levels can be avoided.

PMID- 8254401
TI  - Distribution of gallium-67 in normal and hypotransferrinemic tumor-bearing mice.
AB  - The mechanism by which 67Ga accumulates in tumors is controversial. The most
      popular theory is that 67Ga binds to transferrin and gains access to cells by the
      transferrin receptor. However, substantial evidence suggests that uptake of 67Ga
      may not be universally mediated by transferrin in tumors. To determine whether
      transferrin is required for uptake of 67Ga in vivo, we compared the uptake of
      67Ga by two types of implanted tumors and by normal tissues in normal and
      severely hypotransferrinemic strains of Balb/C mice. One type of tumor was
      strongly gallium-avid in normal mice; the other was not. Uptake of 67Ga by normal
      soft tissues was markedly less in hypotransferrinemic than in normal mice. Uptake
      of 67Ga by bone was equivalent in the two types of mice. For the more gallium
      avid tumor, uptake of 67Ga was similar and the ratio of tumor-to-background
      activity was substantially higher in the hypotransferrinemic than in the normal
      mice. For the less gallium-avid tumor, uptake was significantly less in
      hypotransferrinemic than in normal mice. These data suggest that uptake of 67Ga
      by bone and by some tumors may be a transferrin-independent process.

PMID- 8254402
TI  - Synthetic peptide immunogens for the development of a cardiac myosin light chain
      1 specific radioimmunoassay.
AB  - To determine if the presence of cardiac light chains in blood could be used to
      detect acute myocardial infarction, we developed a specific light chain
      immunoassay. A synthetic peptide sequence specific for human cardiac ventricular
      myosin light chain 1 (VLC1) was synthesized and designated P348. This peptide
      coupled to keyhole limpet hemocyanin was used as an immunogen to obtain murine
      monoclonal antibodies specific for VLC1. Five monoclonal antibodies were
      obtained. One of these designated Mab-8E3 reacted equally well with both the
      synthetic peptide and VLC1. Although the 8E3 antibody is specific for VLC1, the
      use of HPLC purification of skeletal muscle myosin light chain 1 demonstrated
      that VLC1 is present in human skeletal muscle. The clinical utility of the assay
      was tested in 18 patients with creatine kinase (CK) and ECG documented acute
      myocardial infarction. VLC1 was below the limit of detection (< 1 ng/ml) in sera
      obtained from healthy volunteers and patients without myocardial infarction or
      chest pain. In contrast VLC1 was elevated in the serum of all 18 patients with
      acute myocardial infarction. Combining the two test results at the time of
      admission resulted in 83% of patients having detectable serum levels of one or
      both markers.

PMID- 8254403
TI  - Assessment of radiolabeled stabilized F(ab')2 fragments of monoclonal
      antiferritin in nude mouse model.
AB  - The biodistribution of 111In-labeled stabilized fragments of monoclonal
      antiferritin was studied in nude mice bearing a human hepatoma tumor xenograft.
      Pharmacokinetics and tumor targeting of fragment Fab'-linker-Fab' fragment
      molecules (stabilized F(ab')2) were compared to unmodified F(ab')2 fragment
      molecules and immunoglobulin G (IgG). Significant differences were observed in
      tumor and normal organ uptake at 12, 24, 48 and 72 hr. Tumor retention of
      stabilized F(ab')2 fragments was approximately 2.5-fold higher than of unmodified
      F(ab')2 at 48 hr. Blood clearance for stabilized F(ab')2 was relatively faster
      than intact IgG, while unmodified F(ab')2 cleared more rapidly from the
      circulation. Kidney radioactivity of unmodified F(ab')2 was at least two times
      higher than kidney radioactivity of stabilized F(ab')2 at all time points.
      Stabilized F(ab')2 demonstrated 40% less liver uptake than intact IgG. In these
      studies with nude mice, substantial retention of stabilized F(ab')2 in tumor and
      significant reduction in liver and kidney uptake of these fragments indicated
      that they could also have a higher therapeutic ratio than IgG or unmodified
      F(ab')2 in human patients.

PMID- 8254404
TI  - Biodistribution and imaging studies of technetium-99m-labeled liposomes in rats
      with focal infection.
AB  - We have recently developed a procedure to label liposomes containing reduced
      glutathione (GSH) with 99mTc using the lipophilic chelator,
      hexamethylpropyleneamine oxime (HMPAO). In the present study, we evaluated the
      use of 99mTc-liposomes to detect focal infection sites in rats. Rats were
      infected in the thigh by intramuscular injection with Staphylococcus aureus
      followed 24 hr later by an intravenous injection of 99mTc-liposomes, 67Ga
      citrate, or 99mTc-human serum albumin (HSA). The animals were imaged under a
      gamma camera and subsequently killed at 4, 24 or 48 hr for tissue biodistribution
      studies. In contrast to infected rats receiving 67Ga-citrate or 99mTc-HSA,
      abscesses were prominently localized within 2 hr in rats after 99mTc-liposome
      injection, and continued to increase in activity up to 24 hr. Abscess-to-muscle
      ratios calculated from 24-hr biodistribution data obtained from tissue sampling
      were 35.3 +/- 7.6 for 99mTc-liposomes, 4.1 +/- 0.7 for 67Ga-citrate and 8.0 +/-
      1.0 for 99mTc-HSA. These studies show the potential of using 99mTc-liposomes to
      localize infection.

PMID- 8254405
TI  - A malignant melanoma imaging agent: synthesis, characterization, in vitro binding
      and biodistribution of iodine-125-(2-piperidinylaminoethyl)4-iodobenzamide.
AB  - In order to develop improved radiopharmaceuticals for imaging malignant melanoma,
      we have synthesized and characterized 125I-and 131I-labeled (2
      piperidinylaminoethyl)4-iodobenzamide (PAB). In vitro binding profiles of IPAB
      and N-(2-diethylaminoethyl)4-iodobenzamide (IDAB, a structurally related analog
      of IPAB) for a variety of neurotransmitter receptors suggested that both IPAB and
      IDAB possessed a high sigma-1 affinity and a low affinity for sigma-2 sites. In
      vitro homologous competition binding studies of [125I]PAB with human malignant
      melanoma cell A2058 showed that the tracer was bound to the cells with a high
      affinity (Ki = 6.0 nM) and that the binding was saturable. Biodistribution
      studies in nude mice implanted with human malignant melanoma xenografts showed
      good tumor uptake (3.87% ID/g at 1 hr, 2.91% ID/g at 6 hr and 1.02% ID/g at 24
      hr) of [125I]PAB. High tumor-to-nontarget organ ratios were obtained at 24 hr
      postinjection. Tumor-to-blood, liver, muscle, lung, intestines, heart and brain
      ratios at 24 hr were 17.80, 3.88, 94.58, 14.29, 10.87, 37.07 and 90.01,
      respectively. Tumor imaging with [131I]PAB in a nude mice model xenografted with
      human malignant melanoma at 24 hr clearly delineated the tumor with very little
      activity in any other organ. These results demonstrate that sigma-1 receptors
      could be used as external markers for malignant melanoma.

PMID- 8254406
TI  - Technetium-99m-labeled chemotactic peptides: comparison with indium-111-labeled
      white blood cells for localizing acute bacterial infection in the rabbit.
AB  - The biodistribution and infection imaging properties of 99mTc-labeled formyl
      methionyl-leucyl-phenylalanyl-lysyl-hydrazinonicotinamide (99mTc-HP) were
      compared with 111In-labeled leukocytes (111In-WBCs) in rabbits with E. coli
      infections. Groups of six animals were co-injected with 1 mCi of 99mTc-HP plus
      0.05 mCi of 111In-WBCs and serial scintigrams were acquired from 3 to 6 hr and 18
      hr postinjection. After acquiring the final images, the animals were killed and
      biodistribution was determined. At all imaging times, the distributions of 99mTc
      HP and 111In-WBCs were similar and the sites of infection were well visualized
      with both radiopharmaceuticals. The target (infected muscle) to background
      (contralateral normal muscle) ratios (T/B) were: 3.38 +/- 0.46, 3.80 +/- 0.37 and
      10.87 +/- 1.44 for 99mTc-HP and 1.71 +/- 0.04, 1.81 +/- 0.26 and 3.79 +/- 0.83,
      for 111In-WBCs at 3, 6 and 18 hr postinjection, respectively. The average ratio
      of T/B ratios (99mTc-HP-to-111In-WBCs) was 2.99 +/- 1.88, with no value less than
      unity. T/B ratios calculated from direct tissue sampling were significantly
      higher for 99mTc-HP than for 111In-WBCs (33.6:1 versus 8.1:1, p < 0.01). These
      differences were primarily due to increased absolute accumulation of 99mTc-HP
      (0.102%ID/g versus 0.024%ID/g, p < 0.01) in infected muscle rather than a
      difference in accumulation in normal skeletal muscle. These results indicate that
      99mTc-HP yields target-to-background ratios greater than or equal to those
      achievable with 111In-WBCs probably as a result of an increase in absolute
      accumulation at the site of infection.

PMID- 8254407
TI  - Thallium-201 myocardial SPECT in Bland-White-Garland syndrome: two adult patients
      with inferoposterior perfusion defect.
AB  - A myocardial 201TI SPECT examination was conducted both prior to and following
      surgery of two adult patients with an anomalous left coronary artery originating
      from the pulmonary artery (Bland-White-Garland syndrome). In this syndrome, the
      anterior wall is usually affected first. Preoperative examination demonstrated an
      inferoposterior perfusion defect. In both patients, the right coronary artery was
      markedly dilated, and a significant left-to-right shunt formation was observed.
      Both patients were diagnosed as possibly having coronary steal syndrome. A
      prolonged inadequate blood supply to the right coronary region may cause
      inferoposterior cardiomyopathy. In the postoperative examination, myocardial
      perfusion markedly improved in one patient whose preoperative SPECT showed
      redistribution in a delayed scan. Thallium-201 SPECT was therefore found to be
      useful in assessing both the preoperative and postoperative myocardial perfusion.

PMID- 8254408
TI  - Carcinoma in a transplanted kidney detected with MAG3 scintigraphy.
AB  - We report on two cases of infiltrative renal tumor developing in two kidney
      transplant recipients from a single cadaveric donor source. Interestingly, while
      this is only the second case of a de novo renal allograft tumor, both were
      morphologically infiltrative. The fact that both tumors were infiltrative may be
      secondary to immunosuppression therapy. While computed tomography (CT) evaluation
      of suspected renal pathology provides excellent anatomical detail, renal
      transplant recipients are initially evaluated using ultrasound and renal
      scintigraphy to avoid contrast reagents which could further impair renal
      function, as well as to reduce the image procedure cost and the patient radiation
      dose. Unfortunately, infiltrative tumors may be isoechoic on ultrasound,
      providing a confusing or conflicting report when compared to scintigraphic
      findings. This case report is significant radiographically because the original
      neoplasm was initially detected using technetium-99m-labeled
      mercaptoacetyltriglycine (99mTc-MAG3) scintigraphy and was not appreciated by
      sonographic studies, even retrospectively. This case demonstrates the usefulness
      of 99mTc-MAG3 scintigraphy to follow-up evaluations of renal transplants by
      providing detailed anatomical information as well as functional analysis of the
      kidney.

PMID- 8254409
TI  - Detection of hypervascular brown tumors on three-phase bone scan.
AB  - A patient with hyperparathyroidism secondary to chronic renal failure had
      multiple bony lesions with increased activity on both immediate static as well as
      delayed scintiphotos. One lesion in the distal femur was also exceptionally hot
      on the flow phase. Plain radiographs demonstrated lytic lesions with sclerotic
      margins and a narrow zone of transition. Open biopsy revealed histology
      consistent with brown tumor (osteoclastoma).

PMID- 8254410
TI  - Comparison of radionuclide bone scans and magnetic resonance imaging in detecting
      spinal metastases.
AB  - A retrospective comparison was made between 99mTc-MDP bone scans and
      corresponding spine MR images in 35 patients who had complementary studies within
      2 mo. Bone scans were performed with planar imaging of the entire body and MRI
      was performed with a 1.5 tesla signal scanner using standard techniques with T1-
      and T2-weighted images. There were 18 male and 17 female patients diagnosed with
      cancer prior to these studies. Cancer diagnoses included 14 prostate, 12 breast,
      1 bladder, 2 renal, 2 lung, 1 each of esophagus, melanoma, myeloma and
      adenocarcinoma of unknown primary cancer. Of the regions compared, 69 were
      positive for bony metastases by MRI and 63 regions by bone scans. Thirty-eight
      regions were concordantly positive and 56 regions concordantly negative. No
      patients with entirely positive bone scans were negative by MRI, but one patient
      was entirely positive by MRI but negative by a bone scan. At least one region was
      discordantly read in 21 patients. Distribution of positive regions was similar on
      bone scan and MRI. The greatest number and proportion of discordant readings
      occurred in the lumbar regions and more frequently in patients with prostate
      cancer. Considering its widespread availability and the ease of performing a
      whole-body survey for metastasis, radionuclide bone scanning remains the study of
      choice for initial evaluation of patients with cancer. However, MRI is an
      excellent complementary technique when bone scan findings are inadequate for
      answering clinical questions. MRI appears to be quite sensitive and probably more
      specific for metastasis in certain locations of the spine.

PMID- 8254411
TI  - Is the whole really the sum of the parts?

PMID- 8254412
TI  - Comparison of anatomically-defined versus physiologically-based regional
      localization: effects on PET-FDG quantitation.
AB  - The potential of anatomic imaging to improve the quantitative accuracy of
      functional brain imaging through refined regional definition is widely accepted.
      However, there are little data addressing the impact of approach to regional
      localization on quantitation of metabolic images in the absence of gross
      structural pathology. We compared MRI-based versus PET-based approaches to the
      analysis of PET 18F-fluorodeoxyglucose (FDG) images using a standard adjustable
      template based on simple geometric regions. For the MRI-based approach, templates
      and individual regions were adjusted to each individual's anatomy, whereas the
      PET-based definition involved only global proportional adjustment of the standard
      templates. Metabolic rates for glucose and volume-to-whole brain ratios were
      determined by two operators for 78 volumes of interest in five subjects. Pairwise
      correlations indicated high interoperator agreement for each approach and high
      intraoperator agreement for MRI-based versus PET-based metabolic values. The
      stability of the metabolic rates and ratios among operators and analysis
      approaches was supported by low coefficients of variation across measurements and
      small average differences in paired comparisons. Thus, within the current spatial
      resolution of PET imaging, quantitation of metabolic images is relatively robust
      to image analysis approach in the absence of gross structural abnormality. To
      take advantage of the greater quantitative accuracy promised by high-resolution
      anatomic and functional imaging, more refined delineation of anatomic images will
      be necessary.

PMID- 8254413
TI  - Estimation of upper limits on human radiation absorbed doses from carbon-11
      labeled compounds.
AB  - Radiation absorbed dose estimates for short-lived PET tracers are commonly based
      on biodistributions in rodents which (because of more rapid distribution and
      other species differences) may have limited relevance to humans. The initial
      purpose of this study was to estimate an intravenously injectable quantity of 11C
      which could not, on a priori grounds, exceed regulatory limits on radiation
      absorbed doses for individual organs. Upper limits on organ cumulative activities
      were estimated by assuming that 11C-labeled compounds are instantaneously
      distributed in the blood plasma, and then transferred solely and irreversibly to
      a single organ. The rate-constant (min-1) for each organ was taken to be its
      fractional cardiac output, since the plasma volume of 3 liters is recirculated
      each minute. The method was extended by using measured time courses of
      radioactivity in human arterial plasma available from previous PET studies with
      several 11C compounds in place of the assumption that the injected radioactivity
      was initially instantaneously distributed throughout the plasma. Calculations for
      11C L-deprenyl, cogentin, cocaine, N-methylspiperone, putrescine and 2-deoxy-D
      glucose, assuming transfer limited to a single organ, gave the kidneys rather
      than the thyroid as critical organ in each case. The upper-limit self-doses were
      140, 210, 320, 360, 450 and 750 mrad/mCi, respectively, indicating that 34, 24,
      15, 14 and 6.5 mCi, respectively, could be administered in a single PET study.
      These results suggest a strategy for human studies with 11C-labeled compounds: a
      preliminary study at the 3.5-mCi level would yield 11C arterial plasma data which
      could in turn be used to give a refined upper limit on radiation absorbed doses.
      For many 11C compounds, this strategy would demonstrate that sufficient
      radioactivity could be injected to give acceptable human PET images and would
      avoid the death of animals for biodistribution studies.

PMID- 8254414
TI  - Compton scatter compensation using the triple-energy window method for single-
      and dual-isotope SPECT.
AB  - The spatial distribution of scattered photons varies depending on many factors
      such as object size and source distribution. We propose a triple-energy window
      (TEW) scatter compensation method for determining position-dependent Compton
      scatter. We estimated the count of primary photons at each pixel in the acquired
      image using the 24% main window centered at the photo peak energy and 3 keV
      scatter rejection windows on both sides of the main window. We conducted a
      physical evaluation of this method using phantoms and also applied this method to
      patients in a clinical trial. The TEW method performed Compton scatter
      compensation with good accuracy.

PMID- 8254415
TI  - Measurement of pharmacokinetics of yttrium-86 radiopharmaceuticals with PET and
      radiation dose calculation of analogous yttrium-90 radiotherapeutics.
AB  - This study was performed to demonstrate the quantitative in vivo assessment of
      human pharmacokinetics of 90Y-radiotherapeutics using the positron-emitting
      substitute 86Y and PET. This technique is illustrated in a patient with
      disseminated bone metastases from breast cancer who was injected with 100 MBq of
      86Y-citrate as an analog of the commercially available radiotherapeutic 90Y
      citrate. Whole-body distribution was measured with a PET camera 4, 10, 21, 28 and
      45 hr postinjection. Uptake data were determined from reconstructed transverse
      PET images by regions of interest placed in normal bone tissue, liver and
      metastases. Images of coronal and sagittal whole-body sections were obtained by
      reformatting the transverse PET images. The ratio of activity concentration in
      metastases to that in normal bone ranged from 1.5:1 to 3.5:1. Of the injected
      tracer, 13.4% was found in the skeleton and 0.43% in the metastasis with the
      highest 86Y concentration. Radiation doses per 1 MBq of injected 90Y-citrate were
      calculated from 86Y-citrate data and data from MIRD pamphlets 5 and 11. The doses
      were 1.01 MGy/MBq for red marrow, 593 microGy/MBq for the liver and approximately
      3.5 MGy/MBq for the most conspicuous metastases. This study demonstrates that the
      use of PET via 86Y allows an individual in vivo quantification of activity uptake
      and radiation dose of both normal tissue and tumor in pain treatment with 90Y
      labeled radiotherapeutics.

PMID- 8254416
TI  - Hypertrophic cardiomyopathy complicated with ventricular aneurysm and myocardial
      necrosis.

PMID- 8254417
TI  - Bone scintigraphy: Part 1. Oncology and infection.

PMID- 8254418
TI  - Bone scintigraphy: Part 2. Orthopedic bone scanning.
AB  - Bone scanning provides a functional assessment of skeletal pathology not
      available with conventional radiography or special radiographic techniques such
      as CT and MRI. Bone scanning detects osteoblastic activity associated with many
      forms of orthopedic skeletal disease. Several of the more common orthopedic
      applications of bone scanning have been described above, while equally important
      topics such as prothesis loosening, avascular necrosis, and the reflex
      sympathetic dystrophy syndrome were not considered. Thus, for a great range of
      benign skeletal pathology, bone scanning can provide the orthopedic surgeon with
      practical information concerning the cause of the patient's pain, the true
      significance of otherwise questionable radiographic findings, the extent of
      disease and the results of orthopedic surgical treatment.

PMID- 8254419
TI  - Bone scintigraphy: Part 3. Bone scanning in metabolic bone disease.

PMID- 8254420
TI  - A ticket to ride: peptide radiopharmaceuticals.
AB  - Over the past three decades, biospecific imaging agents have evolved from large
      proteins (i.e., antibodies) to antibody fragments (i.e., F(ab')2 and Fab
      fragments) to smaller "molecular recognition units" such as Fv fragments, antigen
      binding domain fragments and small biologically active peptides. The smaller size
      of these molecules confers desirable pharmacokinetic properties, such as higher
      target-to-background ratios and faster blood clearance, that are favorable for
      imaging. Molecular engineering techniques now permit the peptide to carry the
      radionuclide-binding group in its structure while maintaining high-affinity
      binding to the receptor site. An important component to this system is the
      ability to radiolabel these agents with high specific activity using short-lived
      radionuclides, particularly 99mTc. Recently, the application of small
      radiolabeled biologically active peptides for external imaging of a variety of
      biological processes has received considerable interest. These applications have
      ranged from the current widespread use of somatostatin analogs for imaging
      numerous types of tumors to the development of radiolabeled chemotactic peptides
      for infection imaging. In this review, we will describe many of the parameters
      for the rational development of peptide-based imaging agents, including: classes
      of peptides for imaging, methods for radiolabeling peptides, current biologically
      active peptide-based radiopharmaceuticals and future prospects for this new
      technology.

PMID- 8254421
TI  - "Magic bullets:" from muskets to smart bombs!!!

PMID- 8254422
TI  - Clinical PET: a technology on the brink.

PMID- 8254423
TI  - Thoughts at compline.

PMID- 8254424
TI  - Misleading figure of focal activity in the liver.

PMID- 8254425
TI  - The ambulatory renal monitor.

PMID- 8254426
TI  - In vitro assessment of FDG, methionine and thymidine uptake.

PMID- 8254427
TI  - False-positive scans in papillary thyroid carcinoma.

PMID- 8254428
TI  - Vision, hallucinations, and wannabes, Part 1.

PMID- 8254429
TI  - Health hazard concerns of home care nurses. A staff nurse perspective.

PMID- 8254430
TI  - Health hazard concerns of home care nurses. A nurse executive perspective.

PMID- 8254431
TI  - The chief nursing officer as board member selected legal and ethical issues.

PMID- 8254432
TI  - Financial implications and recommendations for care of ventilator-dependent
      patients.
AB  - Patients who require prolonged mechanical ventilation consume a
      disproportionately large share of healthcare resources and represent a
      significant financial burden for traditional acute care institutions. When these
      patients are evaluated as a population, trends that may facilitate medical and
      financial management emerge. This report examines the demographics,
      cost/reimbursement, and current management of patients who require prolonged
      mechanical ventilation. Recommendations for potential reduction of costs, revenue
      producing alternatives, or both in delivering healthcare to this aggregate are
      also explored.

PMID- 8254433
TI  - Quality improvement through data analysis. Concepts and applications.
AB  - Nurse executives play a key role in quality management and need a working
      knowledge of which data collection and improvement tools to use. This knowledge
      insures effective analysis and decision making necessary to drive department and
      organizational transformation through quality improvement programs. The author
      presents the most frequently used tools for quality improvement, with a focus on
      applications in practice.

PMID- 8254434
TI  - Redesigning nursing practice. The partners in patient care model.
AB  - Several nursing practice models use nurse extenders/partners to extend nurses'
      time. The authors discuss the development, implementation, and evaluation of the
      "partner in patient care" (PIPC) model. Unique aspects of the model are
      emphasized, including use of a collaborative process to generate the design and
      guide the implementation; staff participation throughout the design and
      implementation of the project; and use of evaluation at each phase of the
      implementation process to improve on the outcomes.

PMID- 8254435
TI  - The impact of problem-solving styles of nurse executives and executive officers
      on tenure.
AB  - Stability in the chief nurse executive (CNE) position contributes to
      organizational efficiency, effectiveness, and success; yet, CNE turnover remains
      relatively high. In this study, the relationship between the problem-solving
      styles of CNEs and their chief executive officers (CEOs) and CNE tenure was
      studied. Data showed that the problem-solving style of the CNE/CEO pair was
      related to CNE tenure. The author discusses implications for CNE/CEO pairs and
      for CNEs who value job stability.

PMID- 8254436
TI  - Living the dream. Shared governance in the role of nurse executive.
AB  - After one year of jointly assuming the responsibility for the Vice President's
      position of a 415-bed regional medical center, the directors of nursing analyzed
      the reality of living the dream. The authors discuss the personal issues of power
      and the joys and sorrows of group problem solving and decision making through
      shared governance, and present reactions from various levels of hospital
      personnel to this innovative and unconventional approach to nursing management.

PMID- 8254437
TI  - Developing a restraint use policy for acute care.
AB  - Restraint use has been a recent focus of attention in long-term care facilities.
      The Joint Commission on Accreditation of Healthcare Organizations, the Commission
      on Accreditation of Rehabilitation Facilities, and the Food and Drug
      Administration have devoted attention to the prudent use of restraints. The
      authors address efforts of an acute care facility to comply with these
      regulations.

PMID- 8254438
TI  - Merging nursing departments. An experience.
AB  - In 1979, two of the largest private, not-for-profit hospitals in New York City
      merged to become one institution under the aegis of a single corporate
      administration. The integration of two large and disparate nursing departments,
      each with its own distinct identity and organizational structure, into what would
      become a unified department of nursing with a shared vision and goals was a
      complex task. The author, the nurse executive who oversaw this transition,
      describes the process 12 years after the merger.

PMID- 8254439
TI  - Making it in the managed care environment.

PMID- 8254440
TI  - Nursing leadership and healthcare reform, Part III: Nurse executive role in a
      reformed healthcare system.

PMID- 8254441
TI  - Normal intraocular pressure in children: a comparative study of the Perkins
      applanation tonometer and the pneumatonometer.
AB  - We measured the intraocular pressure (IOP) of 50 normal, cooperative, awake
      children below 5 years of age and 12 normal, volunteer adults with the Perkins
      hand-held applanation tonometer (Perkins) and the Digilab pneumatonographer
      tonometer (Pneuma). Neither sedation, general anesthesia, nor lid specula were
      used. We confirmed others' findings that the normal IOP, measured in the supine
      position with the Perkins, is lower in infants and young children (mean = 5.89 mm
      Hg) than in adults (mean = 13.21 mm Hg; P < .0001). On the other hand, with the
      Pneuma, the supine pediatric IOP (mean = 14.76 mm Hg) was not significantly
      different from the adult sitting IOP (mean = 14.42 mm Hg; P = .497). Regression
      analysis suggests that children and adult Perkins IOP may become equal at around
      age 12 years.

PMID- 8254442
TI  - A cluster of patients with inferior rectus restriction following local anesthesia
      for cataract surgery.
AB  - During a 5-month period, four patients developed contracture of the inferior
      rectus muscle following local anesthesia for cataract surgery in the practice of
      one ophthalmologist. Two anesthesiologists administered retrobulbar anesthesia.
      All patients had persistent vertical diplopia caused by a large hypotropia of the
      operated eye. Forced duction testing revealed marked restriction to elevation of
      the eye. In two patients, MRI demonstrated segmental thickening of the inferior
      rectus muscle, just posterior to the globe. All patients had normal thyroid
      function tests. No patient had a previous history of strabismus. Three of the
      four have had strabismus surgery consisting of recession of the markedly
      restricted inferior rectus muscle on an adjustable suture. These three patients
      have regained fusion and are now asymptomatic.

PMID- 8254443
TI  - Strabismus surgery in patients with myasthenia.
AB  - The efficacy of eye muscle surgery for strabismus in patients with myasthenia is
      not well-documented in the literature. We reviewed the results of strabismus
      surgery in six patients with the confirmed diagnosis of myasthenia. Patients
      selected for surgery had angles of deviation that were stable for at least 5
      months preoperatively. Patient age ranged from 4 to 62 years. All patients were
      exotropic. The four adults had moderate limitation of adduction. Surgery included
      horizontal rectus muscle recession and/or resection in all cases. Three cases
      involved additional surgery of the vertical rectus or superior oblique muscles.
      The mean postoperative follow up was 44 months with a minimum of 7 months. Three
      adults and one child achieved stable satisfactory alignment after one procedure.
      One child required three procedures to achieve satisfactory alignment. The
      results suggest that surgery is a viable option in the management of strabismus
      in selected patients with myasthenia.

PMID- 8254444
TI  - A magnetic resonance imaging study of horizontal rectus muscle palsies.
AB  - The assessment of extraocular muscle function is usually performed indirectly by
      an examination of ocular motility. We have utilized magnetic resonance imaging,
      in both cine and static modes, to directly observe the contractility behavior of
      the extraocular muscles. This noninvasive technique was applied to the study of
      patients with horizontal rectus muscle palsies. In all cases, the palsied muscle
      was of a smaller diameter than its normal counterpart. This size differential was
      noted in all fields of gaze. Additional studies are required to determine the
      relative contributions of denervation atrophy and loss of tonus to this
      diminution of muscle size.

PMID- 8254445
TI  - Advancement of medial rectus muscle to the original insertion for consecutive
      exotropia.
AB  - Twenty-four patients who underwent surgery to correct consecutive exotropia that
      developed iatrogenically after surgical overcorrection were studied
      retrospectively. All patients underwent single or bilateral advancement of the
      medial rectus muscle to the original muscle insertion. The mean preoperative
      exodeviation was 26.7 prism diopters at distance and 35.2 delta at near.
      Postoperatively, in cases receiving advancement of a single medial rectus, the
      mean amount of correction was 23.2 delta at distance and 29.6 delta at near. In
      cases receiving bilateral medial rectus advancement, the mean amount of
      postoperative correction was 26.3 delta at distance and 39.8 delta at near.
      Adduction deficiency was normalized in five patients (71%), while convergence
      insufficiency was improved in only nine patients (45%) after surgery. Twelve
      (50%) patients had binocular single vision at distance on a normal or abnormal
      basis as determined by the Bagolini lens test.

PMID- 8254447
TI  - Vernier acuity cards: a practical method for measuring vernier acuity in infants.
AB  - The feasibility of a practical preferential looking technique, similar to Teller
      acuity cards, was investigated for the assessment of vernier acuity in preverbal
      infants. Forty-two infants ages 1 to 13 months were tested with cards having
      vernier offsets of 2 to 64 minutes of arc and spatial frequencies of 0.25 to 2.0
      cycles per degree. All infants showed a robust preferential looking response to
      the largest vernier offsets. Vernier thresholds decreased with age from 64
      minutes of arc at 1 month to 4 minutes of arc at 13 months. Smaller vernier
      offsets were more readily detectable when embedded in higher spatial frequency
      gratings. Vernier acuity can be assessed in preverbal infants using a
      preferential looking technique similar to that employed with the Teller acuity
      cards. Vernier acuity is known to be more sensitive to amblyopia than grating
      acuity; therefore, this technique may prove useful in the assessment of
      amblyopia.

PMID- 8254446
TI  - The intraoperative oculocardiac reflex as a predictor of postoperative vaso-vagal
      responses during adjustable suture surgery.
AB  - Adjustable suture surgery has become a popular method of strabismus correction in
      those cases in which results are less predictable, such as reoperations, thyroid
      ophthalmopathy, and blind eyes. Complications related to adjustable strabismus
      surgery are, in general, no different than those related to standard surgical
      techniques. We noticed a subgroup of patients who experienced significant vaso
      vagal responses (V-VR) during postoperative adjustment and sought to discover a
      method of identifying these patients prior to adjustment. Sixty patients were
      studied prospectively from July 1991 to July 1992. All patients had surgery under
      general anesthesia and were adjusted 24 hours later. A positive oculocardiac
      reflex (OCR) occurred when a 10% or greater intraoperative change in heart rate
      was associated with traction on an extraocular muscle. A positive V-VR
      postoperatively consisted of one or more subjective findings (dizziness, light
      headedness, nausea, or body temperature changes), and two or more objective
      findings (10% or greater change in heart rate, hypotension, pallor, diaphoresis,
      vomiting, disorientation, or loss of consciousness). Variables studied for
      predictive value included OCR, age, sex, strabismus type, previous surgery,
      muscle adjusted, and systemic disease. Twenty-five patients (41.6%) had a
      positive V-VR during adjustment. Twenty-seven patients (45%) had a positive OCR.
      Eighty-five percent of patients with a positive OCR and 9% of patients with a
      negative OCR had a positive V-VR. Younger patients were also more likely to have
      a positive V-VR. A positive intraoperative OCR under general anesthesia during
      strabismus surgery is highly predictive of a postoperative V-VR during planned
      adjustment.

PMID- 8254448
TI  - Facial asymmetry in superior oblique muscle palsy.
AB  - Facial asymmetry is an underrecognized association or sequela of torticollis in
      congenital or very early onset superior oblique muscle palsy, which when present
      in an adult, helps to confirm chronicity and prevent unnecessary neurologic
      evaluation. Nineteen cases of superior oblique muscle palsy were studied
      prospectively. Of 12 unilateral palsies presenting in adulthood, 9 were
      considered congenital by history and 7 (77%) of these had facial asymmetry. Large
      vertical fusional vergence amplitudes and torticollis, on review of childhood
      photographs, confirmed the early onset of the palsy in each facial asymmetry
      patient. In addition, two children presenting at age 18 months and 3 years of age
      with constant head tilting had facial asymmetry. If torticollis is corrected
      before maturation of the facial structure, resolution of the asymmetry may occur.

PMID- 8254449
TI  - The influence of study habits on myopia in Jewish teenagers.
AB  - The prevalence and degree of myopia were measured in 870 teenagers, males and
      females. We found a statistically significant higher prevalence and degree of
      myopia in a group of 193 Orthodox Jewish male students who differed from the rest
      in their study habits. Orthodox schooling is characterized by sustained near
      vision and frequent changes in accommodation due to the swaying habit during
      study and the variety of print size. A possible myopic effect of this unique
      visual demand is postulated.

PMID- 8254450
TI  - Visual alignment from the midline: a declining developmental trend in normal,
      strabismic, and monocularly enucleated children.
AB  - Children, 1.8 to 5.0 years of age, were asked to sight through a tube at targets.
      There were three groups tested: children with normal binocular vision, children
      with strabismus, and children with one eye enucleated. The younger normal and
      strabismic patients placed the tube midway between the two eyes. Surprisingly,
      the younger enucleated children also placed the tube at the midline. This
      "Cyclops effect" diminished as the children grew older, with a transition to
      sighting monocularly by the age of 4 years. The tendency to align with the
      midline by the younger children, regardless of the degree of their binocular
      vision, presumably is a natural response to a cyclopean projection center in the
      midline. As children mature, they learn to meet the demands of monocular
      preference tasks by aligning objects in front of one eye.

PMID- 8254451
TI  - The ophthalmologic presentation of NF-2 in childhood.

PMID- 8254452
TI  - Iris hemangiomas in infants with periorbital capillary hemangiomas.

PMID- 8254453
TI  - Retinoblastoma presenting with spontaneous hyphema and dislocated lens.

PMID- 8254455
TI  - Fatty acid profiles of the outer membrane of ATCC strains 35405, 35404 and 33521
      of Treponema denticola.
AB  - The fatty acid composition of the outer membrane (outer sheath) of Treponema
      denticola is not known. This study examined the fatty acid profiles of the outer
      membranes of T. denticola ATCC strains 35405, 35404, 33521. Homogeneous outer
      membranes were prepared from the three strains of T. denticola. The fatty acids
      were extracted and converted to methyl esters, and their mass spectra were
      determined with a sensitive Hewlett-Packard 5880A-5970 gas chromatography-mass
      spectrometry system. Fatty acids were identified by comparing the unknown fatty
      acid mass spectra to computer stored known mass spectra standards. Dodecanoic, 2
      hydroxy dodecanoic, tridecanoic, tetradecanoic, pentadecanoic, hexadecanoic, 2
      hydroxy hexadecanoic and octadecanoic acid were found in the assay spirochetes
      yielding correlation indices (r) of 0.8-1.00. Isotetradecanoic acid was found in
      the outer membranes of strains 33521 and 35405 (r = 0.913-0.967). Anteiso
      pentadecanoic and heptadecanoic acids were found in the outer membrane of strains
      33521 and 35404 (r = 0.941-0.996), while cis 9, 12 octadecadienoic was found only
      in the outer sheath of strain 35405 (r = 0.922-0.958). The average concentration
      of dodecanoic, tridecanoic, tetradecanoic, pentadecanoic, hexadecanoic,
      heptadecanoic and octadecanoic acid in the outer membranes of strains 35405,
      35404 and 33521 were as follows. Strain 35404: 138, 178, 845, 296, 751, not
      detected, and 699 nanogram per mg dry weight of the outer membrane. Strain 35404:
      96, 125, 670, 306, 597, 38 and 249 nanograms per mg dry weight of the outer
      membrane. Strain 33521: 323, 135, 1650, 125, 9080, 235 and 618 nanograms per mg
      dry weight of the outer membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254454
TI  - Ankyloblepharon filiforme adnatum in trisomy 18.
AB  - Ankyloblepharon filiforme adnatum (AFA) is a mild form of ankyloblepharon, in
      which there is partial thickness fusion of the central portion of the lid
      margins, sparing the canthi. Although it can be seen as an isolated sporadic
      congenital defect, it is important for pediatric ophthalmologists to be cognizant
      of its possible association with a number of anomalies. One infrequent, but
      nevertheless important association, is with trisomy 18. We present three cases of
      AFA in association with trisomy 18, and emphasize the need for clinicians to
      search for other abnormalities in a newborn presenting with AFA.

PMID- 8254456
TI  - Nifedipine-induced gingival overgrowth in the presence or absence of gingival
      inflammation in rats.
AB  - One adverse effect of nifedipine, a long-acting vasodilator, is gingival
      overgrowth. Preexisting gingival inflammation and/or dental plaque has been
      suggested to be responsible for the progression of this side effect, but the
      precise mechanism is uncertain because of a lack of suitable animal models. A
      study was therefore done to establish an experimental model of gingival
      overgrowth in rats and to investigate the possible involvement of gingival
      inflammation and/or dental plaque in its development. Specific pathogen-free
      Fischer rats (male, 14 days old) were used. Gingival inflammation and dental
      plaque accumulation were induced by infection with Streptococcus mutans MT8148R.
      The nifedipine-treated rats (experimental group) were fed a caries-inducing diet
      containing nifedipine either with or without infection, while the nifedipine
      untreated rats (control group) were fed the same diet, similarly with or without
      the infection. Marked gingival overgrowth was induced in the mandibular molar
      region of nifedipine-treated rats regardless of S. mutans infection, although the
      infection resulted in a further increase in the degree of gingival overgrowth.
      Histological examination of the gingival overgrowth revealed the presence of
      redundant subepithelial connective tissue in the treated rats, and inflammatory
      cell infiltration was apparent only in the tissue of the S. mutans-infected rats
      regardless of the nifedipine administration. These findings suggest that
      nifedipine induces gingival overgrowth in rats either in the presence or absence
      of gingival inflammation and/or dental plaque, although these factors can augment
      the effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254457
TI  - Production and characterization of monoclonal antibodies against bacterial lectin
      of Eikenella corrodens.
AB  - A lectin-like substance (EcLS) was purified from the Eikenella corrodens 1073
      cell and monoclonal antibodies were produced against it to confirm the role of
      EcLS in adhesive properties of E. corrodens such as hemagglutination and
      coaggregation with oral bacteria. Four hybridoma clones were selected. Two of the
      antibodies were of the IgG1 isotype and the others were of the IgG2b isotype.
      These monoclonal antibodies inhibited both the hemagglutination of E. corrodens
      and the coaggregation with Actinomyces viscosus or Streptococcus sanguis. The
      reactivity of the monoclonal antibody to E. corrodens 1073 was significantly
      higher than that to E. corrodens 1080 of which adhesive activity was weaker than
      that of E. corrodens 1073. These findings suggest the difference in adhesive
      properties is due to the difference in the amount of EcLS expressed on the cell
      surface. The immunoelectron microscopic study revealed that EcLS of E. corrodens
      1073 was localized in the outer space of outer membrane, not in cell surface
      appendages such as fimbriae where bacteria possessed adhesin. These results
      suggest that coaggregation of E. corrodens with A. viscosus or S. sanguis was
      mediated by EcLS.

PMID- 8254458
TI  - Immunocytochemical investigation of the rat cementoblast phenotype.
AB  - Recent studies have suggested that cementoblasts may be derived from osteoblast
      progenitor cells, although the cementoblast phenotype has not been extensively
      characterized. This immunocytochemical study was carried out to investigate the
      expression by rat cementoblasts of a number of proteins which are characteristic
      of the osteoblast phenotype. Paraffin sections from developing rat tooth germs
      and from fully formed adult rat teeth with surrounding tissues, were incubated
      with antibodies to type I & III collagen, osteocalcin, transforming growth factor
      beta (TGE beta), and insulin-like growth factor 1 (IGF1). Frozen sections and
      unfixed resin-embedded sections were stained for alkaline phosphatase activity.
      Cementum and bone matrix were strongly positive for type I collagen, although
      there was only weak staining for type III collagen. Cementum was also positive
      for osteocalcin, which was particularly strong in the matrix of acellular
      cementum. Most osteoblasts and cementoblasts of the cellular cementum showed
      intense staining for TGF beta and IGF1, although some cementocytes and osteocytes
      were negatively stained. The osteoblast- specific anti-E11 mAb reacted strongly
      with cementoblasts and newly formed cementocytes in the cellular cementum. Cells
      associated with acellular cementum did not express TGF beta, IGF1 or stain
      positively with anti-E11 antibody at any time during root development.
      Cementoblasts were weakly or negatively stained for alkaline phosphatase in
      contrast to the osteoblasts examined, which may reflect the low level of
      synthetic activity in cementoblasts. These results demonstrate that osteoblasts
      and cementoblasts of cellular cementum share many phenotypic characteristics, and
      also suggest that there may be phenotypic differences between cementoblasts
      associated with cellular and acellular cementum.

PMID- 8254459
TI  - Chemically-modified tetracycline normalizes collagen metabolism in diabetic rats:
      a dose-response study.
AB  - An earlier study indicated that a chemically-modified non-antimicrobial
      tetracycline (4-de-dimethylaminotetracycline; CMT-1) can inhibit excess
      collagenase activity in the connective tissues of diabetic rats, however, the
      optimum oral dose and resulting serum concentration were not determined. In the
      current study, adult male Sprague-Dawley rats (body weight approx. 350 g) were
      made diabetic by streptozotocin injection and administered by oral gavage either
      0, 1, 2, 5, or 10 mg CMT-1 per day. After 3 weeks of drug therapy, the rats were
      killed and gingiva, skin, and serum collected. The tissues were 1) extracted,
      partially purified and analyzed for collagenase activity using [3H-methyl]
      collagen as substrate and SDS-PAGE/fluorography; 2) extracted in neutral salt and
      dilute acid solutions (4 degrees C) to assess collagen solubility; and 3)
      analyzed for hydroxyproline to determine tissue (skin) collagen mass. Serum was
      analyzed for glucose and CMT-1 concentration, the latter by HPLC. Inducing
      diabetes dramatically increased both gingival and skin collagenase activity and
      reduced skin collagen mass by 69.8%. Increasing the oral dose of CMT-1
      progressively increased the serum concentration of the drug from 0.6-6.5
      micrograms/ml and progressively decreased the excessive collagenase activity in
      gingiva and skin (p < 0.01 vs untreated diabetics). Although skin collagen mass
      tended to be increased at all oral doses of CMT-1, only the 5 mg dose effect was
      statistically significant (p < 0.01). The diabetes-induced reduction in collagen
      solubility, a classic abnormality (reflecting excessive collagen crosslinking) of
      this disease, was also normalized by CMT-1 therapy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8254460
TI  - Bursts of periodontal destruction and remission, percolation phase shifts, and
      chaos.
AB  - Bursts of periodontal destruction are modelled as percolation-driven phase shift
      events. Percolation theory, though widely used to study the flow of liquids
      through porous nonliving materials (e.g., soils and rocks), can be applied to
      bacterial or toxicological penetration of living tissue in only an approximate
      sense. However, it seems necessary that some mechanism, fundamentally similar to
      the percolation phase shift, is required to adequately account for bursts.
      Percolation theory is therefore offered as a framework for considering such
      events. A principal finding of percolation theory is the existence of percolation
      thresholds, such that when P, the independent probability that a subregion is
      susceptible to an invading substance, is above the threshold, the region will
      percolate or allow flow through, and when P is below the threshold the region
      will not percolate. This instantaneous transition, from a structure that will
      permit percolation to one that will not, is described as a phase shift. In
      addition, the value of P is postulated to depend on multiple factors which might
      constitute a chaotic system. The nonproportionality of a percolation phase shift
      and the nonpredictability of any specific chaotic event suggest that reliable
      burst predictors may, in theory, not be possible at the level of the individual
      site.

PMID- 8254461
TI  - Postoperative bleeding tendency as a risk factor in Actinobacillus
      actinomycetemcomitans-associated periodontitis.
AB  - Frequent bleeding on probing (BOP) has been considered a risk factor for
      recurrence of periodontitis. In the present study, 29 patients with
      Actinobacillus actinomycetemcomitans-associated periodontitis were enrolled in a
      carefully performed recall system. At 6 sites per tooth, periodontal probing
      depth (PPD), gingival index (GI), plaque index (PlI) and BOP was assessed 6
      weeks, 6 months, 1 and 2 years after comprehensive therapy. Professional
      toothcleaning and subgingival scaling at sites with PPD > or = 5 mm and BOP was
      carried out every 2nd or 3rd month. Subgingival samples from 2 sites, a pooled
      subgingival sample, cheek mucosa, saliva and tongue samples were selectively
      cultivated for A. actinomycetemcomitans after 2 years. Following active therapy,
      8% sites had a PPD of > or = 4 mm, whereas 21% sites bled on probing. After 2
      years, respective figures were 12 and 27%. During maintenance, frequent BOP (> or
      = 3 times at 4 visits) had a predictive value of 0.133 to indicate an increase in
      PPD of > or = 2 mm and a negative predictive value of 0.947. The predictive value
      of no bleeding to indicate a stable site was 0.972, the negative predictive value
      0.078. There was evidence for heterogeneity of associations between increase in
      PPD of > or = 2 mm and > or = 3 times BOP among patients (chi 2(28) = 41.45, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254462
TI  - Relative avidity of serum antibodies to putative periodontopathogens in
      periodontal disease.
AB  - ELISA was used to determine both the avidity and titre of IgG, IgA and IgM
      antibodies to the gram-negative anaerobe, Porphyromonas gingivalis, in twenty
      periodontitis patients enrolled in a longitudinal study of attachment loss and
      eleven non-periodontitis affected subjects. The avidity and titre of IgG
      antibodies to Actinobacillus Actinomycetemcomitans were also examined. A cross
      sectional analysis of the longitudinal patients at baseline and non-periodontally
      affected controls confirmed earlier findings that IgG and IgA antibody titres to
      P. gingivalis were higher in periodontitis patients than in individuals who were
      not periodontally affected. In this cross-sectional analysis, IgG antibody
      avidities to P. gingivalis were not found to be significantly higher in
      periodontitis than in control subjects (p = 0.065). However, indications of the
      potential prognostic value of antibody avidity was demonstrated by the higher IgM
      avidities to P. gingivalis in patients who did not experience attachment loss
      during the three-month monitoring period than in those who did (p = 0.0005).

PMID- 8254463
TI  - Gingival crevicular fluid IL-8: correlation with local IL-1 beta levels and
      patient estrogen status.
AB  - Gingival crevicular fluid (GCF) IL-8 and IL-1 beta levels were determined by
      sandwich enzyme-linked immunosorbent assays. Associations between IL-8 and IL-1
      beta GCF levels, and between these cytokines and patient estrogen status were
      evaluated. IL-8 and IL-1 beta were detected more frequently and in higher
      amounts/30 s GCF sample in estrogen-deficient patients than in estrogen
      sufficient patients. IL-8 and IL-1 beta GCF levels were significantly correlated.
      These findings suggest that GCF IL-8 levels are associated with patient estrogen
      status and local IL-1 beta concentrations.

PMID- 8254464
TI  - Evidence of in vitro development of drug resistance to azidothymidine in T
      lymphocytic leukemia cell lines (Jurkat E6-1/AZT-100) and in pediatric patients
      with HIV-1 infection.
AB  - Clinical reports indicate that the development of drug resistance to AZT after
      chronic administration is common. In order to study this phenomenon, the T-cell
      line Jurkat E6-1 was treated continuously in vitro with low, gradually increased,
      concentrations of azidothymidine (AZT). Initially, 1 microM AZT significantly
      retarded the cell line from reaching confluence. However, after 10 weeks the T
      cell line was able to grow in 10 microM AZT without any evidence of growth
      inhibition. Subsequently, cell isolates could grow continuously in the presence
      of 20, 50, and 100 microM AZT without growth inhibition. These T-cell lines
      (Jurkat E6-1/AZT-10, Jurkat E6-1/AZT-20, Jurkat E6-1/AZT-50, and Jurkat E6-1/AZT
      100) were tested for AZT anabolism using purified [3H]AZT, and the results were
      compared to the wild-type untreated Jurkat E6-1 cell line. Similar intracellular
      AZT anabolites concentrations were determined in all cell lines. However, a four-
      to sixfold lower cellular concentration of mono-, di-, and triphosphate
      anabolites of AZT was determined in the Jurkat E6-1/AZT-10 cell line after 1
      microM AZT incubation and 6.5-fold lower after 10 microM AZT treatment. In
      general, a five- to sixfold reduction in the phosphorylation rates were estimated
      in the AZT resistant T-cell line. Pharmacology studies of [3H]AZT in the Jurkat
      E6-1/AZT-100 cell line showed a much lower level of activation of the pro-drug
      (28-fold), due to lack of thymidine kinase (TK) activity when compared to the
      Jurkat E6-1/AZT-10 T-cell line. A similar level of resistance was obtained at the
      thymidylate (dTMP) kinase level. Concurrently an additional mode of resistance
      (407-fold) was seen on the incorporation of the AZT triphosphate anabolite
      (AZTTP) into cellular DNA. The formation of this cell line in a period of < or =
      4 months coincides with the evidence of the clinical development of "resistance"
      to AZT in patients who receive the drug continuously. In addition, these T-cell
      lines have been infected with HIV, and studies on the development of collaterally
      sensitive regimens are under way.

PMID- 8254465
TI  - Association of immune activation with intravenous heroin use and methadone
      treatment in HIV-1 seropositive and seronegative subjects.
AB  - This study evaluated the effect of continued heroin use during methadone
      treatment on serum neopterin levels in 40 human immunodeficiency virus (HIV) type
      1 seropositive (HIV+) and 70 seronegative (HIV-) intravenous drug users (IVDUs).
      Persistent drug use, determined by urinary evidence of opiates, was more common
      in HIV+ than in HIV- IVDUs (p = 0.01). Serum neopterin concentration, an
      indicator of increased probability of progression to AIDS, was elevated in HIV+
      IVDUs, p < 0.0001 (mean 16.0 nmol/L) compared to that of HIV- IVDUs (mean 10.0
      nmol/L) and in persistent IV drug users compared with abstainers, p < 0.0001. The
      effect of drug use and HIV status on serum neopterin was not explained by
      differences in methadone treatment, age, sex, or total years of i.v. drug use.
      Neopterin decreased in 25 IVDUs, regardless of HIV serostatus, treated with
      methadone for an average of 1.5 years.

PMID- 8254466
TI  - Fusion activity dissociated from replication ability in feline immunodeficiency
      virus (FIV) in human cells.
AB  - Multinucleated-giant-cell formation followed by cell killing was observed after
      cocultivation of the feline immunodeficiency virus (FIV)-producing feline T-cell
      line 3201/FIV with various human cells, including T-cell lines carrying human T
      cell lymphotropic virus type I (HTLV-I). The susceptibility to giant cell
      formation varied with the cell lines tested. Cocultivation of irradiated 3201/FIV
      cells with MT-2 cells resulted in giant cell formation as early as 2 h in
      culture, with striking resemblance to that induced by human immunodeficiency
      virus (HIV). MT-4 cells (HTLV-I positive) and H9 cells (HTLV-I negative) were
      less susceptible than MT-2 to the induction of syncytia. MOLT-4 cells (HTLV-I
      negative) had intermediate sensitivity to syncytia formation. No syncytia were
      observed in the monocytic cell line U-937 (HTLV-I negative). Syncytia formation
      between 3201/FIV and MT-2 cells was inhibited by polyclonal cat anti-FIV antisera
      but not polyclonal cat anti-feline leukemia virus (FeLV) antisera, goat anti
      FeLV, uninfected specific-pathogen-free cat serum, human anti-HTLV-I antisera, or
      normal human and goat serum. Concentrated cell-free FIV supernatant from 3201/FIV
      also induced giant cells of MT-2 cells that were indistinguishable from those
      induced by cocultivation. Giant cells and extensive cell killing associated with
      giant cell formation declined and disappeared within 10 days. Surviving cells
      appeared to be of normal size and grew continuously without expressing FIV
      antigen or releasing infective virus. Although Southern blot analysis using
      probes specific for FIV could not detect proviral DNA in any of the five human
      cell lines cocultured with irradiated 3201/FIV cells, the polymerase chain
      reaction (PCR) technique detected FIV-specific DNA in MOLT-4 cells. DNA from the
      FIV-PCR positive MOLT-4 cells was PCR negative for endogenous FeLV-specific
      sequences, indicating that the MOLT-4 cell DNA was not contaminated with DNA from
      feline cells (i.e., 3201 cells). The FIV-MOLT-4 cells remained PCR positive for
      FIV after 40 passages, suggesting stable integration in the human cell line.
      These findings indicate that FIV is capable of forming proviral DNA in human T
      lymphoid cells by cocultivation, although this FIV-carrying human cell line
      failed to produce replication-competent viruses.

PMID- 8254467
TI  - Therapy for oropharyngeal candidiasis in HIV-infected patients: a randomized,
      prospective multicenter study of oral fluconazole versus clotrimazole troches.
      The Multicenter Study Group.
AB  - A total of 334 HIV-infected patients with oral candidiasis were randomly assigned
      to receive 14 days of treatment with either 100 mg of oral fluconazole once daily
      or 10 mg clotrimazole five times daily. Both treatments were clinically
      effective: 98% of evaluable fluconazole-treated patients and 94% of evaluable
      clotrimazole-treated patients were cured or showed improvement (p = NS).
      Fluconazole was more effective than clotrimazole in eradicating Candida from the
      oral flora by the end of therapy (65% versus 48%) (p = 0.005). In addition,
      patients in the fluconazole-treated group were more likely to remain asymptomatic
      through the second week of follow-up (82.3% versus 50.0%) (p < 0.001). This
      difference was no longer evident by the post-therapy visit during week 4. Seven
      patients treated with clotrimazole and two patients treated with fluconazole
      discontinued therapy because of side effects. Two patients in the fluconazole
      group were withdrawn from therapy because of elevated serum glutamic-oxaloacetic
      transaminase levels, one considered possibly related to drug therapy. Fluconazole
      was as effective as clotrimazole in the treatment of oral candidiasis and
      temporarily provided a more prolonged disease-free state. Future studies are
      needed to define the optimal regimen for both the treatment and prevention of
      recurrent oral candidiasis in HIV-infected patients, addressing special attention
      to the issue of compliance, cost, and emergence of resistance.

PMID- 8254468
TI  - Therapy for oropharyngeal candidiasis in HIV-infected patients.

PMID- 8254469
TI  - Improved outcomes in intensive care units for AIDS-related Pneumocystis carinii
      pneumonia: 1987-1991.
AB  - Respiratory failure due to Pneumocystis carinii pneumonia (PCP) is the most
      common complication requiring an intensive care unit (ICU) for persons with AIDS.
      In this study, we evaluated patterns of ICU use for ICU patients with first
      episode PCP in 15 Veterans Administration Medical Centers from 1987 to 1991.
      Twelve percent of all patients with PCP received care in the ICU. The survival
      rates improved steadily during these years. Although there was little variation
      in the relative frequency of ICU use, the effectiveness of ICU use appeared to
      improve over time. In the more recent years, relatively more survivors and
      relatively fewer nonsurvivors received care in an ICU. Changes in medical
      practice such as adjunctive use of steroids for severe cases of PCP and more
      effective use of scarce resources may account for the improved survival rates for
      patients with PCP who are treated in an ICU.

PMID- 8254470
TI  - Determinants of accrual of women to a large, multicenter clinical trials program
      of human immunodeficiency virus infection. The AIDS Clinical Trials Group.
AB  - To determine factors influencing the enrollment of women in a large multicenter
      human immunodeficiency virus (HIV) clinical trials program in the United States,
      we analyzed enrollment and demographic data of the AIDS Clinical Trials Group
      (ACTG) during the period 1987-90. Women comprised 6.7% of 11,909 ACTG
      participants enrolled in 1987-90. Women entering ACTG trials were significantly
      more likely to be white (48.5%) and less likely to have ever used i.v. drugs
      (22.6%) than U.S. women reported to have AIDS (26.5% were white; 51.0% had ever
      used i.v. drugs, p < 0.0001). In a multiple logistic regression model, specific
      attributes of individual trials did not influence enrollment of women with the
      exception that trials that targeted asymptomatic persons had greater enrollment
      of women. There was wide variation among research units in the percentage of
      women enrolled (1.0-37.5%), and evidence of significant regional variation in the
      ability of units to recruit available women. Units with female principal or
      coprincipal investigators had more than twice the percentage of female enrollment
      as units headed by men (10.8 vs. 5.3%, p < 0.001). Enrollment of women in a large
      HIV clinical trials program was low and appeared to be influenced more by
      demographic and geographic factors that attributes of specific trials. An
      apparent positive influence of female leadership on the enrollment of women
      warrants further study.

PMID- 8254471
TI  - The use of fine needle aspiration cytology in the management of human
      immunodeficiency virus-related non-Hodgkin's lymphoma and Hodgkin's disease.
AB  - We prospectively studied the utility of fine needle aspiration (FNA) to diagnose
      non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) in patients with human
      immunodeficiency virus (HIV) infection and lymphadenopathy. Twenty-one patients
      with a clinical evidence of lymphoma underwent 24 FNA and site-specific tissue
      biopsies. Twenty-two of the 24 biopsy results were consistent with a malignant
      lymphoproliferative neoplasm: NHL (19 cases), HD (two cases), and T-cell lymphoma
      (one case). Two biopsies showed reactive lymphoid hyperplasia consistent with a
      clinical diagnosis of persistent generalized lymphadenopathy. There was an 87%
      correlation (21 of 24) between FNA and biopsy diagnoses. Eighteen of the 19
      biopsy-confirmed NHL cases were diagnosed with FNA. Both cases of HD and the one
      T-cell lymphoma were also diagnosed with aspirate material. In conclusion, the
      FNA in HIV-infected individuals with suspected malignant lymphadenopathy is
      highly sensitive (95%). The FNA, when used in conjunction with the clinical
      appearance, is a useful tool in the management of HIV infection and
      lymphadenopathy.

PMID- 8254472
TI  - A distinctive cytologic pattern for diagnosing tuberculous lymphadenitis in AIDS.
AB  - Tuberculous lymphadenitis (TL) is a very common infection in human
      immunodeficiency virus (HIV)-infected patients. We performed fine-needle
      aspiration biopsy (FNAB) of enlarged lymph nodes in 57 HIV-infected patients to
      evaluate its usefulness in this population. We observed three cytologic patterns
      in 21 patients diagnosed as having TL: granulomatous lymphadenitis (GL) in 4
      FNABs, necrotizing granulomatous lymphadenitis (NGL) in 7 FNABs, and necrotizing
      lymphadenitis (NL) in 12 FNABs. GL and NGL are already well-known and considered
      to be highly suggestive of TL. Our results support the idea that NL should have
      the same diagnostic value as GL or NGL. In the group of 12 patients with NL, TL
      was confirmed in 11 by microbiologic methods (7 by a positive Ziehl-Neelsen stain
      and 4 by a positive Lowenstein culture) and in the remaining patient by a biopsy
      that showed NGL with acid-fast bacilli. We conclude that FNAB is a useful,
      inexpensive, and safe technique for diagnosing TL in HIV-infected patients. The
      finding of a NL pattern is suggestive enough of TL to start antituberculous
      treatment.

PMID- 8254473
TI  - HIV-1 PCR and isolation in seroconverting and seronegative homosexual men:
      absence of long-term immunosilent infection.
AB  - The presence of detectable HIV-1 prior to the appearance of HIV-1-specific
      antibody was assessed in 41 incident infections that occurred during a 6-year
      prospective cohort study. All available antibody-negative samples (n = 138) and
      the first antibody positive sample (n = 41) were tested, under code, by the
      polymerase chain reaction (PCR) in two laboratories and by HIV-1 isolation in a
      third laboratory. Samples were available as long as 66 months and at least 18
      months before seroconversion for 24/41 subjects. An equal number of time-matched
      control specimens from persistently seronegative homosexual men and 103 samples
      from normal blood donors were also tested under code. Samples with discordant
      results were subjected to coded repeat analysis along with appropriate controls.
      All but one of the 41 first antibody-positive specimens (97.6%) were PCR positive
      and 65% were isolation positive. Two control specimens from seronegative
      homosexual men were PCR positive and one was culture positive, but HLA typing
      provided clear evidence of specimen mix-up in the specimen archive. For 37/41
      seroconvertors, all available antibody negative specimens were negative by both
      PCR and virus isolation. In three cases, the specimen obtained 6 months before
      seroconversion was PCR and isolation positive. One specimen, obtained 12 months
      before SC, was PCR positive and isolation negative but was determined to be the
      result of sample contamination. Both PCR and isolation were negative in this
      subject 6 months before SC. In conclusion, we were unable to detect immunosilent
      infection > 6 months before seroconversion in high-risk homosexual men.

PMID- 8254474
TI  - Sex acts, sex partners, and sex budgets: implications for risk factor analysis
      and estimation of HIV transmission probabilities.
AB  - Many epidemiological studies have identified the number of sex partners as a risk
      factor for the acquisition of HIV, but few studies have identified the number of
      sex acts as a risk factor. The seeming lack of importance of the number of sex
      acts as a risk factor has yet to be explained. In this report we conduct an
      exploratory data analysis to evaluate the relationship between the number of sex
      acts and the number of sex partners for heterosexuals. Our results indicate that
      it may be most appropriate to view sexual activity within a sex budget and
      resource allocation framework. We use the results (a) to suggest an explanation
      for why the results from some of the risk factor analysis studies have identified
      a per partnership but not a per act risk, and (b) to assess the implications of
      the relationship for the estimation of heterosexual transmission probabilities
      for HIV.

PMID- 8254475
TI  - Demographic characteristics of retroviral infections (HIV-1, HIV-2, and HTLV-I)
      among female professional sex workers in Lagos, Nigeria.
AB  - In 1990/1991, 885 prostitutes residing in 11 of the 12 Local Government Areas
      (LGAs) of Lagos State, Nigeria, participated in a cross-sectional study to
      determine current seroprevalence of antibodies to human immunodeficiency virus
      type 1 (HIV-1) and type 2 (HIV-2), and human T-cell lymphotropic virus type I
      (HTLV-I). The overall prevalence of HIV-1 was 12.3%, of HIV-2, 2.1%, and of HTLV
      I, 2.8%. HIV-1 seropositivity did not vary significantly by age, socioeconomic
      class, or nationality, but HIV-1 seroprevalence was significantly elevated for
      prostitutes resident in the Port area of Lagos which serves as a crossroads for
      international and national commerce (OR = 2.3; 95% CI = 1.1, 4.6). HIV-2
      infection was significantly associated with low socioeconomic class (OR = 3.7;
      95% CI = 1.2, 10.8) and non-Nigerian nationality (OR = 6.7; 95% CI = 2.5, 18.4).
      Prevalence of HTLV-I infection increased significantly with age (OR = 2.3; 95% CI
      = 1.0, 5.3). The high seroprevalence of HIV-1 in this survey, compared with
      previous surveys reported in the last several years and the correlation between
      high prevalence and areas of international commerce suggest that HIV-1 is
      spreading in this area of Nigeria. Intensified prevention campaigns are needed to
      address this possible emerging epidemic.

PMID- 8254476
TI  - Effect of differential mortality on risk behavior change in cohort studies.
AB  - Recent theoretical work suggests that reductions in aggregate measures of risk
      behaviors are to be expected during a human immunodeficiency virus epidemic,
      because mortality is likely to be differential with respect to the level of the
      risk behavior. We present and apply a methodology for quantifying the effects of
      differential mortality on risk behavior changes in closed cohort studies. We
      demonstrate that differential mortality has caused 21% of the observed reduction
      in the mean, 29% of the observed reduction in the effective average, and 33% of
      the observed reduction in the variance of a risk behavior in a cohort of gay men.

PMID- 8254477
TI  - First description of endemic HTLV-II infection among Venezuelan Amerindians.
AB  - We describe for the first time the presence of human T lymphotropic virus type II
      (HTLV-II) infection in Venezuela, among the Pume Amerindians living in the
      southern plains of the country. Antibodies to HTLV-II antigens were assessed by
      enzyme immunoassays (Elisa), Western blot, radioimmuno-precipitation, and
      immunofluorescence; titration studies against HTLV-I- and HTLV-II-infected cell
      lines were very useful in the differentiation of HTLV-I and HTLV-II antibodies.
      The HTLV-II general prevalence was 5%; however, there is a striking difference in
      prevalence between the truly isolated villages (0%) when compared to those living
      along the riverside and thus in contact with outsiders (9%). Preliminary evidence
      suggests sexual contact as the main source of transmission. These findings might
      suggest that HTLV-II in Venezuela originated through contact with outsiders
      rather than ancient infection related to the origins of the Pume.

PMID- 8254478
TI  - HTLV-1 but not HTLV-2 found in pygmies from Central African Republic.

PMID- 8254479
TI  - [Microbial enzymes and their inhibitors].
AB  - Several proteolytic enzymes and dehydrogenases of microbial origin were studied
      with special regard to structure-activity relationship. Enzyme genes of Zn
      proteases, subtilisin and pyroglutamyl aminopeptidase from genus Bacillus, prolyl
      endopeptidases from Flavobacterium and Aeromonas, and of protease II from E. coli
      were cloned, sequenced and overproduced in E. coli, their active site structures
      being elucidated by chemical modification as well as by site-directed
      mutagenesis. Homology analysis revealed that there is a prolyl endopeptidase
      family as a new family of serine endopeptidases. In addition, enzymatic
      properties and the primary structures of glutathione-independent formaldehyde
      dehydrogenase of Pseudomonas putida and 7 alpha-hydroxysteroid dehydrogenase from
      E. coli were elucidated. Amino acid sequences deduced from the nucleotide
      sequences of their genes indicated that the former enzyme should be classified
      into a long-chain metallo alcohol dehydrogenase family, and the latter belongs to
      a member of the short-chain nonmetallo-alcohol dehydrogenase family.

PMID- 8254480
TI  - [Absorption and first-pass-effect of salbutamol after intraduodenal and
      intrarectal administration in rabbits].
AB  - To understand the previous result of higher bioavailability of rectal salbutamol
      (SB) compared with oral SB, in situ experiments using rabbit duodenal and rectal
      loop were carried out. After the intravenous (i.v.) and intraportal (i.p.) dosing
      of SB, fraction of dose which avoids the hepatic first-pass-effect (Fh) was
      calculated from the areas under the blood concentration-time curve (AUC). The Fh
      was about 10% and unchanged significantly with increasing i.p. dose (5-20 mg).
      Intraduodenal (i.d.) or intrarectal (i.r.) dosing of SB was made after the i.v.
      and i.p. dosing, and the AUC's and the residual amount in the loop were obtained
      to estimate the parameters. The results of the i.d. and i.r. dosing were as
      follows; for the extent of bioavailability (EBA), 7.7 +/- 1.5% and 14.5 +/- 2.3%,
      for the fraction of dose absorbed (fa), 93.9 +/- 3.7% and 33.8 +/- 3.3%, and for
      the fraction of absorbed SB which avoids first-pass-effects (F), 8.4 +/- 1.9% and
      43.0 +/- 6.0% (mean +/- S. E., n = 4). Consequently, SB dosed i.d. was absorbed
      completely, and received first-pass-metabolism in the mucosa (about 20%) and then
      in the liver (about 90%), which caused the low bioavailability. While, in i.r.
      dosing, SB absorption was poor. However, higher bioavailability was obtained
      owing to about 40% of rectal venous blood flow which bypasses the liver and
      negligible first-pass-metabolism in the mucosa (about 4%).

PMID- 8254481
TI  - [Effect of leaves of Ginkgo biloba on hair regrowth in C3H strain mice].
AB  - Effects of 70% ethanolic extract from leaves of Ginkgo biloba (GBE) on the hair
      regrowth in normal and high butter diet-pretreated C3H strain mice which
      posterior hair we shaved were investigated. GBE showed a promoting effect on the
      hair regrowth. GBE had the inhibitory effects on blood platelet aggregation,
      thrombin activity and fibrinolysis. GBE inhibited the increase of serum the
      triglyceride level in high cholesterol diet-treated rats. These results suggested
      that GBE promotes the hair regrowth and could be used as a hair tonic.

PMID- 8254482
TI  - [Synthesis and antimicrobial properties of methyl 3-O-alkyl-glucopyranosides].
AB  - A new type of nonionic surface-active agents containing sugars as the hydrophilic
      group were synthesized and evaluated for their antimicrobial activity. Methyl 6
      deoxy-3-O-dodecyl-6-halo-D-glucopyranoside derivatives showed powerful
      antimicrobial activity, but no significant differences were observed on the
      activity with regard to the kinds of anomers as well as halogen atoms.

PMID- 8254483
TI  - Effects of humidity and temperature on in vitro dissolution of carbamazepine
      tablets.
AB  - The rate and extent of dissolution of various approved marketed carbamazepine
      (CBZ) tablets exposed to 33, 52, 75, and 97% relative humidities at both room
      temperature and 40 degrees C, and saturated water vapor at room temperature were
      compared to fresh unstressed tablets. The dissolution data indicate that exposure
      of CBZ tablets to high humidity and temperature can have a profound effect on
      tablet disintegration and dissolution. The dissolution rates of some batches of
      CBZ products exposed to 97% humidity at 40 degrees C or saturated water vapor at
      room temperature were drastically reduced in only 6-7 days.

PMID- 8254484
TI  - X-ray structural characterization of anhydrous metronidazole benzoate and
      metronidazole benzoate monohydrate.
AB  - Single crystals of anhydrous metronidazole benzoate and its monohydrate were
      isolated from the same aqueous solution and studied by X-ray diffraction.
      Anhydrous metronidazole benzoate gives crystals belonging to the triclinic space
      group P1 and, at ambient temperature, a = 6.649 (2), b = 8.666(1), c = 11.940(3)
      A, alpha = 76.70(2)degrees, beta = 76.72(2)degrees, gamma = 87.56(2)degrees, V =
      651.6(3) A3, Z = 2, and Rw(F) = 0.053. Metronidazole benzoate monohydrate gives
      crystals belonging to the triclinic space group P1 and, at ambient temperature, a
      = 7.544(1), b = 7.990(1), c = 12.329(4) A, alpha = 94.33(2)degrees, beta =
      97.40(2)degrees, gamma = 101.36(1)degrees, V = 718.6(3) A3, Z = 2, and Rw(F) =
      0.041. Thermomicroscopy, differential scanning calorimetry, and thermogravimetry
      were used for initial characterization of the title species and to investigate
      possible phase changes on heating. The crystal structure analyses revealed that
      the metronidazole benzoate molecule adopts different conformations in the two
      crystal forms. Crystal cohesion in the anhydrous form is due to van der Waals
      interactions only, whereas in the monohydrate, there is strong intermolecular
      hydrogen bonding mediated by water molecules. Computer-generated X-ray powder
      patterns for the two species are distinctly different and serve as reference for
      their identification.

PMID- 8254485
TI  - Aqueous acidic degradation of the carbacephalosporin loracarbef.
AB  - The aqueous degradation of the carbacephalosporin loracarbef under moderately
      acidic conditions (pH range, 2.7-4.3) is described. Structures of a total of 10
      compounds isolated by preparative reversed-phase HPLC have been proposed. Five of
      these 10 degradation compounds arose from hydrolysis of the beta-lactam ring
      followed by structural changes in the six-membered heterocyclic ring. Four
      compounds form from intermolecular reactions of loracarbef to form dimeric
      structures with peptide linkages. The remaining compound resulted from oxidation
      of the primary amine to a hydroxylamine. Pathways for the formation of these
      compounds from the parent loracarbef are proposed.

PMID- 8254486
TI  - An experimental method for determining the Hildebrand solubility parameter of
      organic nonelectrolytes.
AB  - A three-solvent system was used to determine the Hildebrand solubility parameters
      of organic nonelectrolytes. The experimental Hildebrand solubility parameter
      represents a weighted average of the mole fraction solubilities of the solute in
      these three individual solvents (ethyl acetate, 1-propanol, and 1,2-propanediol).
      The solvent system estimated the Hildebrand solubility parameters of solutes
      within a range from 8.9 to 14.8 (cal/cm3)2(1). Deviations ranged from 0.8 to
      12.9%, with the highest value at the extreme and well within 10% at the median.
      Estimation of the Hildebrand solubility parameters of solutes within a wider
      range and with somewhat better accuracy was made with a five-solvent system
      (hexane, ethyl acetate, 1-propanol, 1,2-propanediol, and water).

PMID- 8254487
TI  - Development of a sensitive and specific radioimmunoassay for benztropine.
AB  - A benztropine RIA based on polyclonal antisera raised in New Zealand white
      rabbits has been developed. The drug-protein conjugates employed had a variety of
      moles of benztropine hemisuccinate coupled per mole of protein (bovine serum
      albumin or bovine thyroglobulin). Six antisera were developed and the one with
      the highest titer was further evaluated for its cross reactivity to N
      desmethylbenztropine (4%) and the antipsychotic agents fluphenazine,
      flupenthixol, chlorpromazine, and haloperidol (all < 1%). The selected antiserum
      demonstrated sufficient sensitivity to measure benztropine from 0.156 to 100
      ng/mL plasma in a 200-microL plasma sample, with a mean CV of < 6%. The RIA was
      applied to the analysis of steady-state plasma samples obtained from patients
      undergoing treatment with benztropine and plasma samples obtained from human
      volunteers and dogs orally dosed with the drug. Both the human and dog plasma
      samples, when analyzed after hydrolysis with beta-glucuronidase/sulfatase,
      demonstrated increments in benztropine concentrations, suggesting the drug may be
      undergoing biotransformation to phase II metabolite(s). In addition, when
      benztropine was selectively extracted from the unhydrolyzed plasma samples, there
      was a significant decrease in drug level, which further suggested that the
      antiserum cross reacted with phase II metabolite(s). The shape of the plasma
      concentration versus time profile obtained from the dog studies suggested that
      the drug might also undergo enterohepatic recycling.

PMID- 8254488
TI  - Calorimetric studies of dissolution of hydroxypropyl methylcellulose E5 (HPMC E5)
      in water.
AB  - The interaction of water with polymers is important because it directly or
      indirectly affects various properties such as rheological and transport
      properties. In this study, the hydration/dissolution of a hydrophilic polymer was
      investigated by calorimetric techniques. Hydroxypropyl methylcellulose E5
      (Methocel, HPMC E5) was used as the model polymer. A water-insoluble, hydrophobic
      polymer, ethyl cellulose E4 (Ethocel, EC E4), was selected for comparison. The
      number of moles of non-freezing and freezing water were determined by
      differential scanning calorimetry. Moles of non-freezing water per polymer repeat
      unit were 6.2 +/- 1.3 and 1.6 +/- 0.3 for HPMC E5 and EC E4, respectively. The
      hydration/dissolution of HPMC E5 was exothermic, with a total heat of dissolution
      of -24.1 +/- 1.1 cal/g (n = 4). The heat of hydration of water-insoluble EC E4
      was -2.6 cal/g (n = 2). The specific heat capacity value of HPMC E5 increased due
      to the addition of water. The heat of solution and an increase in specific heat
      capacity values were associated mainly with the addition of tightly bound water
      to the polymer. The dissolution of HPMC E5 in water is believed to have
      endothermic and exothermic components. In summary, the study provided insight
      into the dissolution of a representative hydrophilic polymer in water. The heat
      of solution and the specific heat capacity values were mainly dependent on the
      addition of tightly bound water.

PMID- 8254489
TI  - In vitro percutaneous permeation of betamethasone and betamethasone 17-valerate.
AB  - The percutaneous permeation and sorption isotherm (equilibrium) profiles of
      betamethasone and betamethasone 17-valerate were estimated in an in vitro study
      with excised human skin. Corticosteroids were measured by HPLC. The stratum
      corneum (dry weight)/water partition coefficient of betamethasone 17-valerate was
      20 times greater than that of betamethasone. Nevertheless, when aqueous
      saturation was maintained in the donor solution, the mean steady-state flux of
      betamethasone 17-valerate through split-thickness skin was 57.6 ng/cm2/h, whereas
      that of betamethasone was 15.2 ng/cm2/h. This was presumably because the aqueous
      saturation concentration of betamethasone (60 micrograms/mL) was 11 times greater
      than that of betamethasone 17-valerate (5.4 micrograms/mL), so that the
      calculated saturation concentrations of the two corticosteroids in stratum
      corneum were within a factor of 2. However, the drug amounts or concentrations of
      the more lipophilic corticosteroid (betamethasone 17-valerate) attained in viable
      layers (viable epidermis and dermis) at steady state were predicted to be greater
      than those of the less lipophilic corticosteroid (betamethasone) when the results
      in the permeation and equilibrium studies were interpreted by a mathematical
      model. The drug distribution pattern predicted (i.e., that a more lipophilic
      corticosteroid preferentially partitions into viable layers) was reasonable when
      compared with that observed in the permeation study. The mean drug amount of
      betamethasone 17-valerate in dermis was four times greater than that of
      betamethasone, whereas the drug amounts of both corticosteroids in epidermis were
      similar to each other.

PMID- 8254490
TI  - Differential elimination of synthetic butyric triglycerides in vivo: a
      pharmacokinetic study.
AB  - New butyrate derivatives were synthesized to investigate the residence time of
      potent butyric acid in vivo. These derivatives were triglycerides in which one,
      two, or three butyric acid molecules were bound to glycerol or to mono- and
      dipalmitic esters of glycerol. Pharmacokinetic studies showed that a constant
      plasma level of each compound was maintained for a long time; all molecules had
      identical volumes of distribution, but differed about their mean residence time.
      Triesters in which palmitic acid was present displayed no toxicity and seemed to
      be even more stable in the organism; this may be due to their adsorption on the
      tissue. Other triglycerides constituted by butyric acid and various long fatty
      acids may be synthesized and useful in long-term clinical treatment.

PMID- 8254491
TI  - Quantitative determination of cis-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)
      cyclohexyl)-benzamide and three of its metabolites in plasma by high-performance
      liquid chromatography.
AB  - A sensitive HPLC method was developed for simultaneous quantitation of cis-3,4
      dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzamide and three of its
      metabolites in dog plasma. The method involved selective solid-phase extraction
      of the compounds of interest from dog plasma and HPLC separation of the analytes
      on a cyano column. Absorbance of the column effluent was monitored at 230 nm by a
      UV detector. The analytical procedure has a linear range of 10 ng/mL to 20
      micrograms/mL, with a low limit of quantitation of 10 ng/mL for each analyte. The
      accuracy and intra- and interassay precision for each compound were < or = 11% in
      the concentration range evaluated. Applicability of this method to the
      quantitation of 1 and its metabolites was assessed in a preclinical
      pharmacokinetic study.

PMID- 8254492
TI  - Improved bioavailability of para-boronophenylalanine by cyclodextrin
      complexation.
AB  - This study was undertaken to develop an oral dosage form for para
      boronophenylalanine (BPA) plus cyclodextrin (CD) for use in the thermal neutron
      capture therapy for malignant melanoma. Powders of the BPA and CD complexes were
      obtained in a molar ratio of 1:2. X-ray diffraction of the BPA-CD complexes
      showed halo patterns that indicated that each complex was in a new solid state as
      an amorphous compound. The enhancement of BPA solubility by glucosyl (G1)- and
      maltosyl (G2)-alpha-CD was greater than that with the other CDs. The isolation
      rate of BPA from its complex was different for each BPA-CD complex. The
      bioavailability of BPA in rats was improved with oral administration of the BPA
      alpha-CD, G1-alpha-CD, and G2-alpha-CD complexes. In contrast, a complex of BPA
      and dimaltosyl (G2G2) or G2-beta-CD, which had low release rate and low
      solubility, did not improve the bioavailability of BPA. These results indicate
      that the solubility and release rate of BPA from a complex in solution are
      important for the bioavailability of BPA after oral administration of BPA-CD
      complexes.

PMID- 8254493
TI  - Oral pharmacokinetics of carbamazepine in dogs from commercial tablets and a
      cyclodextrin complex.
AB  - The extent of absorption of carbamazepine from a 2-hydroxypropyl-beta
      cyclodextrin/carbamazepine complex was significantly greater and the rate of
      absorption was faster when compared with an immediate-release carbamazepine
      tablet in the dog. Six dogs were dosed orally in a two-way crossover study in
      which the tablet was compared with an equivalent dose of the complex in solution.
      The area under the curve of concentration versus time for the complex was 5.6
      times greater than the tablet, whereas the mean time to reach maximum
      concentration for the tablet was 1.4 hours versus 0.5 hours for the complex. The
      complex, therefore, had a greater rate and extent of absorption. A rapidly acting
      and better absorbed carbamazepine product has the potential to decrease the daily
      dose of carbamazepine, increase its utility as emergency treatment of epileptic
      seizures, and provide an acceptable alternative dosage form in patients who are
      unable to swallow tablets.

PMID- 8254494
TI  - Model for a controlled-release drug delivery safety system with permeable and
      erodible coatings.
AB  - Models of drug delivery devices that employ erodible permeable coatings must take
      care to avoid the unacceptably high rate of release that arises as the erodible
      coating disappears and the barrier to drug release vanishes. One solution to this
      safety problem has been to exhaust the drug reservoir just before this condition
      occurs. This design has the disadvantage of placing demands of high accuracy on
      the quality control in the fabrication of the device. A drug delivery system of
      cylindrical symmetry is proposed that uses two permeable coatings on a drug
      containing core. Only the outer of the two coatings is erodible; the inner safety
      coating and the core are inert. Calculations are performed to design the device
      that can yield constant drug delivery rates while avoiding the possibility of
      explosive late drug release.

PMID- 8254495
TI  - Methods for estimating pharmacokinetic parameters should be thoroughly tested.

PMID- 8254496
TI  - Use of a solute-container interaction to determine protein binding: application
      to long-chain fatty acids.

PMID- 8254497
TI  - Novel formulation strategies for improving oral bioavailability of drugs with
      poor membrane permeation or presystemic metabolism.
AB  - The oral route is most preferred for chronic drug therapy. Poor oral
      bioavailability has the consequences of more variable and poorly controlled
      plasma concentrations and drug effects, in addition to possibly increased product
      cost. In this review, the most common causes of low oral bioavailability are
      categorized, and formulation strategies to improve bioavailability are
      summarized. Various methods that can be used to help identify the cause of low
      bioavailability are discussed. The focus of this article is on poor membrane
      permeation and presystemic degradation problems; solubility/dissolution rate
      problems are discussed only briefly. Poor membrane permeation and presystemic
      degradation problems are typically encountered in the efforts to develop oral
      proteins, peptides, and peptide mimics. Formulation strategies reviewed include
      the use of metabolism inhibitors, membrane permeation enhancers, ion pairing and
      complexation, and particulate carriers. Also reviewed are lipid and surfactant
      formulations, which have been shown to increase bioavailability by various
      mechanisms and which are only beginning to be understood and optimized.

PMID- 8254498
TI  - Degradation and inactivation of antitumor drugs.
AB  - Chemical methods for the degradation of 11 antineoplastic drugs [etoposide,
      teniposide, bleomycin, mitomycin C, cisplatin, cis-dichloro-trans-dihydroxy
      bis(isopropylamine) platinum IV (CHIP), cyclophosphamide, ifosfamide, carmustine,
      lomustine, and methotrexate] were investigated. The success of the degradation
      procedures was assessed by HPLC and degree of biological inactivation by
      mutagenicity assays. The most widely applicable procedure was oxidation with
      potassium permanganate or 5.25% sodium hypochlorite solution (bleach). Oxidation
      completely degraded and inactivated etoposide, teniposide, bleomycin, mitomycin
      C, and methotrexate. In addition, oxidation followed by nucleophilic substitution
      resulted in the complete degradation and inactivation of cyclophosphamide and
      ifosfamide. Although carmustine and lomustine were chemically degraded by
      treatment with acidic potassium permanganate, the resulting reaction mixtures
      remained mutagenic. Therefore, this procedure cannot be recommended. The platinum
      containing compounds, cisplatin and CHIP, were rendered nonmutagenic by reaction
      with sodium diethyldithiocarbamate. These easily performed, relatively safe
      procedures can be used to prevent exposure to mutagenic wastes and spills in the
      hospital setting.

PMID- 8254499
TI  - Intrahepatic distribution of hydrochlorothiazide and quinidine in rats:
      implications in pharmacokinetics.
AB  - The intrahepatic distributions of a nonmetabolized drug, hydrochlorothiazide
      (HCTZ) and a highly metabolized drug, quinidine (QD), were studied separately in
      five anesthetized rats during steady-state intravenous infusion. Liver samples
      (20-24) from various parts (0.1-0.2 g each) at the end of infusion were collected
      from each rat and analyzed for drug concentration by HPLC. The distribution of
      HCTZ in various macro regions appears quite "homogeneous," with a CV of drug
      concentration for each rat ranging from 2.6 to 4.7% (grand mean, 3.7 +/- 0.8%),
      whereas that of QD seems less "homogeneous," with a CV ranging from 8.5 to 28.3%
      (grand mean, 15.6 +/- 7.7%). The above results indicate that drugs that are not
      complicated by hepatic metabolism may tend to show more "homogeneous"
      distribution and those that are highly metabolized and/or known to strongly bind
      to hepatic tissue component(s) may show less "homogeneous" distribution. The
      results from the present QD study are in contrast with the general, much more
      heterogeneous distribution found in an isolated in situ perfusion study reported
      earlier. The implication of the present study in physiological pharmacokinetic
      and hepatic modeling is discussed.

PMID- 8254500
TI  - Comparative pharmacokinetics of free muramyl tripeptide phosphatidyl ethanolamine
      (MTP-PE) and liposomal MTP-PE.
AB  - The comparative pharmacokinetics of free MTP-PE (muramyl tripeptide phosphatidyl
      ethanolamine) and MTP-PE entrapped in negatively charged multilamellar liposomes
      (liposomal MPT-PE) was evaluated in rats at a bolus intravenous (i.v.) dose of
      0.2 mg/kg and in dogs at a bolus i.v. dose of 0.1 mg/kg. Additional studies were
      performed with the free form in rats (1.4 mg/kg, bolus i.v.) and dogs (1 mg/kg,
      bolus i.v.) and with the liposomal form in dogs (0.5 mg/kg, bolus i.v.). Plasma
      samples were obtained at various times up to 48 h postinjection and assayed for
      the drug by a chemiluminescence immunoassay. The pharmacokinetic data regarding
      liposomal MTP-PE describe the distribution of free drug released from liposomes
      and total drug concentrations. The present studies demonstrate that the
      distribution characteristics of MTP-PE changed dramatically depending on the
      dosage form. The elimination kinetics of free MTP-PE from blood is substantially
      slower than that of the liposomal drug. For liposomal MTP-PE, free drug levels in
      plasma are very low compared with free MTP-PE. In rats at a dose of 0.2 mg/kg,
      96% of MTP-PE contained in liposomes is removed from the plasma compartment 10
      min after injection, and in dogs at a dose of 0.1 mg/kg, 100% of MTP-PE contained
      in liposomes is removed in the same time period. This rapid phase of liposome
      clearance is followed by a slower rate of clearance for the remainder of the
      liposomes in rats at a dose of 0.2 mg/kg and in dogs at a dose of 0.5 mg/kg.

PMID- 8254501
TI  - The relation between stimulus and response in olfactory receptor cells of the
      tiger salamander.
AB  - 1. Olfactory receptor cells were isolated from the adult tiger salamander
      Ambystoma tigrinum and the current in response to odorant stimuli was measured
      with the whole-cell voltage-clamp technique while odorants at known
      concentrations were rapidly applied for controlled exposure times. 2. Three
      odorants, cineole, isoamyl acetate and acetophenone, were first applied at 5 x
      10(-4) M. Out of forty-nine cells tested, 53% responded to one odorant only, 22%
      to two odorants and 25% to all three odorants. 3. The amplitude of the current in
      response to a given odorant concentration was found to be dependent on the
      duration of the odorant stimulus and reached a saturating peak value at 1.2 s of
      stimulus duration. 4. The current measured at the peak of the response for
      odorant steps of 1.2 s as a function of odorant concentration was well described
      by the Hill equation for the three odorants with Hill coefficients higher than 1
      and K1/2 (odorant concentration needed to activate half the maximal current)
      ranging from 3 x 10(-6) to 9 x 10(-5) M. 5. It is concluded that olfactory
      receptor cells are broadly tuned and have a low apparent affinity for odorants,
      integrate stimulus information over time, and have a narrow dynamic range.

PMID- 8254502
TI  - Charge inactivation in the membrane of intact frog striated muscle fibers.
AB  - 1. Charge movements were compared in normally polarized and depolarized intact
      frog muscle fibres under voltage clamp. 2. The membrane capacitance was linear
      through positive control steps made consistently from a holding voltage of -10
      mV, in agreement with earlier reports from cut fibres. 3. A shift in holding
      voltage from -90 to -10 mV reduced both the absolute amount and the voltage
      dependence of charge movement elicited by voltage steps imposed from a fixed
      conditioning voltage of -180 mV. The charge transferred by steps from -180 to -20
      mV was 43.8 +/- 1.14 nC/microF in fully polarized fibres and 21.7 +/- 1.49
      nC/microF in the same depolarized fibres (means +/- S.E. of the mean; four
      fibres). 4. Charge movement in response to steps from -90 to -20 mV increased
      from 10.4 +/- 1.60 nC/microF to 28.4 +/- 2.42 nC/microF (five fibres) within 30s
      of changing the holding voltage from -10 to -90 mV. 5. The same fibres also
      showed significant charge movement between voltages of -180 and -90 mV. However,
      shifts in holding voltage did not significantly alter the maximum value of this
      charge, around 10-11 nC/microF. 6. Membrane capacitance as measured by small
      steps to a voltage of -90 mV remained constant despite holding potential changes,
      or lidocaine (10 mM) treatment. 7. The same results were obtained whether the
      above procedures were applied to fibres exposed to normal extracellular [Ca2+],
      or in Ca(2+)-free media. In both cases tubular cable corrections did not affect
      the results. 8. These findings suggest independent charge I and charge II systems
      in which inactivation of charge I is not associated with its interconversion into
      charge II.

PMID- 8254503
TI  - Action of histamine on single smooth muscle cells dispersed from the rabbit
      pulmonary artery.
AB  - 1. The effects of histamine, noradrenaline and caffeine were studied in freshly
      dispersed smooth muscle cells from the rabbit pulmonary artery using the
      perforated patch technique. 2. In potassium-containing solutions at a holding
      potential of -50 mV all three agents evoked net inward and outward currents. At 0
      mV only an outward current was observed and this response was not produced in
      potassium-free conditions. 3. In K(+)-free solutions the reversal potential (Er)
      of the inward current was dependent upon the transmembrane anion gradient but not
      on the cation gradient. Thus all three agents produced an increase in potassium
      and chloride conductance. 4. Bath-applied histamine evoked repetitive potassium
      and chloride currents in many cells. Bath-applied noradrenaline and caffeine, to
      a lesser extent, also caused repetitive currents but the brief ionophoretic
      application of noradrenaline never produced oscillations in membrane current. 5.
      Histamine reduced or abolished the amplitude of spontaneous transient potassium
      and chloride currents. 6. Histamine-induced currents were blocked by caffeine (10
      mM) but could be recorded in Ca(2+)-free bathing solutions. 7. It is concluded
      that in the rabbit pulmonary artery histamine evokes single and oscillatory
      membrane potassium and chloride currents which are mediated by the release of
      calcium from intracellular caffeine-sensitive stores.

PMID- 8254504
TI  - Cytosolic calcium homeostasis in bovine parathyroid cells and its modulation by
      protein kinase C.
AB  - 1. The effects of protein kinase C (PKC) activators and inhibitors on the
      mechanisms regulating cytosolic Ca2+ homeostasis in dissociated bovine
      parathyroid cells loaded with fura-2 were examined. 2. Stepwise increases in the
      concentration of extracellular Ca2+ (from 0.5 to 2 or 3 mM) elicited transient
      followed by sustained increases in the concentration of intracellular free Ca2+
      ([Ca2+]i). Cytosolic Ca2+ transients reflected the mobilization of intracellular
      Ca2+ and influx of extracellular Ca2+ whereas sustained increases in [Ca2+]i
      resulted from the influx of extracellular Ca2+. Brief (1-2 min) pretreatment with
      phorbol myristate acetate (PMA) shifted the concentration-response curve for
      extracellular Ca(2+)-induced cytosolic Ca2+ transients to the right without
      affecting the maximal response. Cytosolic Ca2+ transients elicited by
      extracellular Mg2+ were similarly affected by PMA. 3. These effects of PMA were
      mimicked by various other activators of PKC with the rank order of potency PMA >
      phorbol dibutyrate > bryostatin , > (-)indolactam V > mezerein. Isomers or
      analogues of these compounds that do not alter PKC activity (4 alpha-phorbols and
      (+)indolactam V) did not alter [Ca2+]i. 4. PKC activators depressed evoked
      increases in [Ca2+]i when influx of extracellular Ca2+ was blocked with Gd3+.
      Cytosolic Ca2+ transients elicited by extracellular Mg2+ in the absence of
      extracellular Ca2+ were similarly inhibited by PKC activators. Activation of PKC
      thus inhibits the mobilization of intracellular Ca2+ elicited by extracellular
      divalent cations. 5. Increases in the concentration of extracellular Ca2+ caused
      corresponding increases in the formation of [3H]inositol 1,4,5-trisphosphate
      ([3H]InsP3). Pretreatment with PMA shifted the concentration-response curve for
      extracellular Ca(2+)-induced [3H]InsP3 formation to the right without affecting
      the maximal response. 6. PKC activators also caused some depression of steady
      state increases in [Ca2+]i elicited by extracellular Ca2+. In contrast, PMA did
      not affect increases in [Ca2+]i elicited by ionomycin or thapsigargin. 7. Ba2+
      was used to monitor divalent cation influx. PMA decreased the rate of rise of the
      fluorescent signal elicited by extracellular Ba2+. 8. All these effects of PKC
      activators on [Ca2+]i were blocked or reversed by staurosporine at concentrations
      (30-100 nM) that inhibited PKC activity in parathyroid cells. Staurosporine alone
      potentiated cytosolic Ca2+ responses evoked by submaximal concentrations of
      extracellular divalent cations. 9. PKC thus depresses both the mobilization of
      intracellular Ca2+ and the influx of extracellular Ca2+ in parathyroid cells. The
      effects on [Ca2+]i provide evidence for a Ca2+ receptor on the surface of
      parathyroid cells that uses transmembrane signalling mechanisms common to some
      other Ca(2+)-mobilizing receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254505
TI  - Protein kinase C modulates hormone secretion regulated by extracellular
      polycations in bovine parathyroid cells.
AB  - 1. The role of protein kinase C (PKC) in the regulation of parathyroid hormone
      (PTH) secretion was examined in dissociated bovine parathyroid cells. 2.
      Increasing the concentration of extracellular Ca2+ from 0.5 to 2 mM inhibited PTH
      secretion by 60-80%. Similar depressive effects on secretion were obtained by
      increasing the concentration of extracellular Mg2+ from 1 to 7 mM or by adding
      La3+ (to 40 microM). The PKC activator phorbol myristate acetate (PMA) depressed
      PTH secretion at the lower and potentiated secretion at the higher concentrations
      of extracellular Ca2+, Mg2+ or La3+. The inhibitory effect of PKC on secretion
      correlated positively with the magnitude of the inhibitory effect elicited by
      elevated extracellular Ca2+. 3. The stimulatory effects of PKC activators on PTH
      secretion were reversed completely and the inhibitory effects were reversed
      partially by the PKC inhibitor staurosporine. Staurosporine alone did not affect
      secretion at low (0.5 mM) or high (2 mM) concentrations of extracellular Ca2+ but
      it did depress secretion at intermediate concentrations (around 1 mM) of
      extracellular Ca2+. 4. The stimulatory effects of PKC activators on secretion
      were overcome by increases in the concentration of extracellular Ca2+ (to 5 or 10
      mM) or La3+ (to 100 microM). In contrast, increasing the concentration of
      extracellular Mg2+ to 11 or 19 mM did not alleviate the potentiating effects of
      PKC activators. The different results obtained with Ca2+ and Mg2+ could not be
      explained by their different effects on cytosolic Ca2+ and suggests that
      different cations can have varying degrees of efficacy to activate functional
      responses linked to the Ca2+ receptor on bovine parathyroid cells. 5. PTH
      secretion stimulated by isoprenaline was not affected by PKC activators or
      staurosporine. Similarly, the inhibitory effects of extracellular ATP gamma S on
      secretion were unaffected by PKC activators. These results show that PKC
      activators affect specifically PTH secretion regulated by extracellular
      polycations. 6. The stimulatory effect of PKC activators on secretion parallels
      its inhibitory effects on [Ca2+]i and inositol trisphosphate formation, showing
      that PKC blunts the mechanisms associated with extracellular Ca(2+)-induced
      inhibition of secretion. The specificity of these actions suggests that PKC acts
      at a very early step of stimulus-secretion coupling in parathyroid cells,
      specific to that used by extracellular polycations and perhaps involving the Ca2+
      receptor.

PMID- 8254506
TI  - Beta-adrenergic enhancement of inhibitory synaptic activity in rat cerebellar
      stellate and Purkinje cells.
AB  - 1. Using the tight-seal whole-cell recording technique, we studied the effects of
      noradrenaline (NA) on the spontaneous inhibitory synaptic currents (IPSCs) of
      stellate and Purkinje cells in rat cerebellar slices. 2. In both types of cells,
      NA (10 microM) induced a marked increase in the frequency of the IPSCs. This
      effect was observed both in the absence and in the presence of TTX in the saline
      bathing the cerebellar slices. 3. The NA-induced increase in frequency of IPSCs
      and miniature IPSCs (mIPSCs) in the two cell types was mimicked by bath
      applications of isoprenaline (10 microM) and of the adenylyl cyclase activator
      forskolin (20 microM). Neither phenylephrine nor clonidine changed the frequency
      of IPSCs in stellate or Purkinje cells. 4. In stellate cells, the beta-agonists
      and forskolin had variable effects on the amplitudes of both IPSCs and mIPSCs.
      None of these compounds altered the amplitude of mIPSCs in Purkinje cells. 5. The
      responses to local applications of GABA to Purkinje cells were unchanged by bath
      applications of beta-adrenergic agonists or forskolin. A decrease in the response
      to GABA after treatment with these agents was observed in half the stellate cells
      examined. 6. We conclude that the major effect of NA on stellate and Purkinje
      cells is an increase in the frequency of occurrence of spontaneous inhibitory
      synaptic currents. This action is exerted through the activation of beta
      adrenergic receptors and is probably mediated by an intracellular mechanism
      involving cAMP. The beta-adrenergic modulation of IPSC frequency takes place at
      the presynaptic level and may involve a change in the process of transmitter
      release.

PMID- 8254507
TI  - Ca2+ entry through Na(+)-Ca2+ exchange can trigger Ca2+ release from Ca2+ stores
      in Na(+)-loaded guinea-pig coronary myocytes.
AB  - 1. The ionized cytosolic calcium concentration ([Ca2+]i) was monitored in voltage
      clamped coronary myocytes at 36 degrees C and 2.5 mM [Ca2+]o using the Ca2+
      indicator indo-1. [Ca2+]i was transiently increased by fast application of 10 mM
      caffeine, and the mechanisms involved in decay of [Ca2+]i were analysed. 2.
      Resting [Ca2+]i was 166 +/- 62 nM (mean +/- S.D.). Caffeine increased [Ca2+]i
      within 1-2 s to 1618 +/- 490 nM. In the continuous presence of caffeine [Ca2+]i
      fell close to resting values with a half-decay time of 5.0 +/- 1.6 s. Wash-out of
      caffeine induced an undershoot of [Ca2+]i to 105 +/- 30 nM. When caffeine was
      applied repetitively the [Ca2+]i transients were of reduced amplitude indicating
      that the store had lost a part of releasable Ca2+. 3. After a 1 s caffeine
      application [Ca2+]i decayed with a half-time of 2.3 +/- 0.8 s to the undershoot
      of 112 +/- 57 nM. The decay of [Ca2+]i was largely prevented by 3 mM [La3+]o;
      after wash-out of La3+ [Ca2+]i fell to the resting value without an undershoot.
      The results demonstrate that La(3+)-sensitive Ca2+ extrusion contributes to the
      decay of the [Ca2+]i transient and to the undershoot. 4. With 10 mM [Na+]i,
      sodium removal from the bath incremented [Ca2+]i in three out of ten cells by 71
      +/- 11 nM; in the other cells [Ca2+]i did not change. In the absence of
      extracellular sodium the decay of [Ca2+]i after wash-out of caffeine was not
      retarded. 5. To stimulate Na(+)-Ca2+ exchange, cells were dialysed with pipette
      solution containing 150 mM NaCl. Elevation of [Na+]i had no significant effect on
      the resting [Ca2+]i (180 +/- 47 nM) or on the caffeine-induced [Ca2+]i transients
      (peak 1614 +/- 530 nM, half-time of decay 3 s, undershoot 107 +/- 40 nM). 6. With
      150 mM [Na+]i, sodium removal resulted in an increase of [Ca2+]i, although
      responses varied in amplitude (from 130 to 2300 nM) and rate of rise. In the
      absence of sodium [Ca2+]i remained elevated. After a 1 s caffeine application the
      undershoot of [Ca2+]i was abolished in sodium-free solution. When caffeine was
      applied in sodium-free solution, the [Ca2+]i transient decayed to a sustained
      level and the following caffeine response was attenuated. 7. With 150 mM [Na+]i,
      the effects of sodium removal were strongly suppressed by a preceding depletion
      of the Ca2+ stores with caffeine. Ryanodine pretreatment abolished the caffeine
      induced [Ca2+]i transients and reduced [Ca2+]i response due to sodium
      removal.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254508
TI  - Calcium spikes and calcium plateaux evoked by differential polarization in
      dendrites of turtle motoneurones in vitro.
AB  - 1. The ability of dendrites in turtle motoneurones to support calcium spikes and
      calcium plateaux was investigated using differential polarization by applied
      electric fields. 2. Electric fields were generated by passing current through
      transverse slices of the turtle spinal cord between two plate electrodes. The
      linear extracellular voltage gradient generated by the field implied that the
      tissue was ohmic and homogeneous. 3. The transmembrane potential at the cell body
      of motoneurones was measured as the voltage difference between an intracellular
      and an extracellular microelectrode. 4. In normal medium an applied field induced
      synaptic activity as well as intrinsic polarization of motoneurones. Synaptic
      activity was suppressed by tetrodotoxin (TTX, 1 microM). 5. In the presence of
      TTX and tetraethylammonium (TEA, 1-5 mM), applied fields evoked multicomponent
      Ca2+ spikes in both the soma-hyperpolarizing and soma-depolarizing direction of
      the field. The different components of Ca2+ spikes were discrete and additive.
      High amplitude components had higher threshold and faster time course and were
      followed by larger after-hyperpolarizations, than low amplitude components. The
      frequency of field-evoked regenerative responses was relatively insensitive to
      somatic bias current. 6. TTX-resistant Ca(2+)-mediated plateau potentials
      promoted by apamin were evoked by differential polarization in both the soma
      depolarizing and soma-hyperpolarizing direction. 7. It is concluded that Ca2+
      channels responsible for Ca2+ spikes and Ca2+ plateaux are present in dendrites
      of spinal motoneurones of the turtle.

PMID- 8254509
TI  - Non-electrolyte solute permeabilities of human placental microvillous and basal
      membranes.
AB  - 1. Permeability to non-electrolytes of isolated microvillous and basal membranes
      from human term placenta was measured using stopped-flow light-scattering
      techniques. The studied solutes were urea, ethylene glycol, glycerol, creatinine,
      erythritol, arabitol and mannitol. 2. At 37 degrees C, permeability of the
      microvillous membrane to mannitol and urea was 0.30 +/- 0.02 x 10(-6) cm/s (mean
      +/- S.E.M.) and 3.2 +/- 0.2 x 10(-6) cm/s, respectively. The corresponding
      permeabilities for the basal membrane were 1.2 +/- 0.1 x 10(-6) cm/s (mannitol)
      and 4.4 +/- 0.3 x 10(-6) cm/s (urea). The basal membrane was substantially more
      permeable to hydrophilic solutes than the microvillous membrane. This is probably
      due to differences in lipid composition, as illustrated by membrane cholesterol
      content, which was found to be approximately 50% lower in the basal as compared
      to the microvillous membrane. 3. Similarities between permeabilities in placental
      membranes and lipid bilayers and the linear relationship noted between solute
      hydrophobicity and placental permeability suggested that solutes permeate both
      human syncytiotrophoblast membranes by a solubility/diffusion mechanism. In the
      microvillous membrane this was supported by data obtained for activation energies
      (> 10 kcal/mol) and reflection coefficients (close to 1). In the basal membrane,
      low activation energies for glycerol and urea and a low reflection coefficient
      for urea indicated that these solutes may, in part, share a common pathway with
      water. 4. It was estimated that the placental permeability to molecules with a
      molecular weight under 200 observed in vivo can, to a great extent, be accounted
      for by transcellular permeation.

PMID- 8254510
TI  - Inositol trisphosphate-mediated Ca2+ influx into Xenopus oocytes triggers Ca2+
      liberation from intracellular stores.
AB  - 1. Inositol 1,4,5-trisphosphate (InsP3) functions as a second messenger by
      liberating Ca2+ from intracellular stores and by promoting influx of
      extracellular Ca2+. We examined whether Ca2+ influx modulates intracellular Ca2+
      liberation in Xenopus oocytes by fluorescence monitoring of cytosolic free Ca2+
      together with voltage clamp recording of Ca(2+)-activated Cl- membrane currents.
      Sustained activation of membrane Ca2+ permeability was induced by intracellular
      injections of a non-metabolizable InsP3 analogue, 3-deoxy-3-fluoro-D-myo-inositol
      1,4,5-trisphosphate (3-F-InsP3), and Ca2+ influx was controlled by applying step
      changes in membrane potential to alter the driving force for Ca2+ entry. 2.
      Negative-going potential steps evoked intracellular Ca2+ signals comprising two
      components; an initial transient peak followed by a slower rise. The initial
      transient grew steeply over a narrow (ca 40 mV) voltage range but then increased
      little with further polarization, whereas the second component showed a nearly
      linear voltage dependence. 3. The transient Ca2+ signal continued to rise almost
      unchanged when Ca2+ influx was interrupted by stepping the potential to more
      positive values after brief hyperpolarization. In contrast, Ca2+ levels declined
      monotonically when positive-going steps were applied after longer intervals
      during the second component of the Ca2+ signal. 4. Large Ca(2+)-dependent
      transient inward (T(in)) membrane currents were evoked during the rising phase of
      the initial Ca2+ signal, but little current was associated with the second
      component of the Ca2+ signal. 5. The T(in) currents evoked by hyperpolarization
      were mimicked at fixed clamp potential by re-admitting Ca2+ to the bathing
      solution, and by flash photolysis of caged Ca2+ loaded into the oocyte. 6. T(in)
      currents were strongly inhibited by prior release of Ca2+ from InsP3-sensitive
      intracellular stores, and vice versa. Experiments with paired hyperpolarizing
      pulses and paired photorelease of InsP3 showed that responses to both stimuli
      recovered with similar time courses. 7. We conclude that the transient Ca2+
      signal and associated T(in) current evoked by hyperpolarization arise because
      Ca2+ entering the oocyte triggers regenerative release of Ca2+ from InsP3
      sensitive intracellular stores. Since membrane currents evoked by liberated Ca2+
      were much greater than those evoked by Ca2+ entry per se, a major function of
      InsP3-mediated Ca2+ entry may be to modulate the activity of intracellular Ca2+
      stores.

PMID- 8254511
TI  - Characterization of an outward potassium current in canine jejunal circular
      smooth muscle and its activation by fenamates.
AB  - 1. A perforated patch clamp technique was used to study an outward potassium
      current in freshly dissociated circular smooth muscle cells of the canine
      jejunum. 2. A voltage-dependent outward current was identified which was highly
      potassium selective, weakly holding voltage sensitive, increased its open
      probability at -65 mV, and reached unit open probability at +5 mV. 3. Quinidine
      (0.1-1 mM) and tetraethylammonium ion (TEA) (10-50 mM), blocked the potassium
      current in a dose-dependent manner. Blockade of the outward potassium current was
      accompanied by membrane depolarization which reversed on removal of the blocker
      from the bathing solution. 4. Mefenamic and flufenamic acids, non-steroidal anti
      inflammatory agents in the fenamate group, were potent activators of the current.
      Activation was accompanied by hyperpolarization of the membrane with a mean shift
      in the membrane voltage of 22 mV. 5. It was concluded that the outward potassium
      current is a major regulator of the resting membrane voltage in isolated circular
      smooth muscle cells of the canine jejunum. Fenamates activated this current with
      potentially profound effects on cellular excitability.

PMID- 8254512
TI  - Purine nucleoside transport and metabolism in isolated rat jejunum.
AB  - 1. The absorption and metabolism of purine nucleosides and their constituent
      bases has been investigated by perfusion through the lumen of isolated loops of
      rat jejunum. In control perfusions and those with luminal purines or purine
      nucleosides, high-performance liquid chromatography (HPLC) revealed uric acid as
      the only detectable purine in the mucosal epithelial layer and the serosal
      secretions unless the xanthine oxidase inhibitor allopurinol was present. 2.
      Adenosine (0.5 mM) was quantitatively deaminated to inosine in the lumen after
      perfusion for 30 min. 3. Luminal inosine and hypoxanthine (0.15-1.0 mM) increased
      the serosal uric acid concentration significantly (P < 0.001); at 0.5 and 1.0 mM
      the nucleoside gave a significantly greater (P < 0.01) rate of serosal uric acid
      appearance than the base. 4. Luminal guanosine (0.05-0.50 mM) and guanine (0.05
      0.15 mM) increased the serosal uric acid concentration significantly (P < 0.001);
      with 0.15 mM nucleoside the serosal uric acid appeared significantly faster (P <
      0.01) than it did from the base. 5. Luminal allopurinol (0.3 mM) inhibited
      xanthine oxidase by 80% and reduced serosal purine appearance significantly (P <
      0.01) from luminal guanine, hypoxanthine and inosine. With allopurinol, guanosine
      (0.1 and 0.15 mM) and inosine (0.1-1.0 mM) gave significantly higher (P < 0.01)
      total serosal purine concentrations than their respective bases. 6. Inosine and
      guanosine were cleaved to their respective bases plus ribose phosphate by the
      action of a cytoplasmic nucleoside phosphorylase, which was found to have widely
      different Michaelis constants (Km; 318 +/- 45 and 41.4 +/- 3.6 microM for inosine
      and guanosine, respectively) and maximum velocities (Vmax; 79.3 +/- 4.0 and 20.5
      +/- 0.05 mumol min-1 (mg protein)-1 for inosine and guanosine, respectively). 7.
      We conclude that hypoxanthine and guanine absorbed by rat small intestine are
      oxidized to uric acid which is released in the serosa. The corresponding
      nucleosides are split by phosphorolysis after absorption and the resulting purine
      bases are converted to uric acid which appears on the serosal side with similar
      quantities of ribose phosphate.

PMID- 8254513
TI  - Intracellular calcium and vasopressin release of rat isolated neurohypophysial
      nerve endings.
AB  - 1. Monitoring of [Ca2+]i and vasopressin secretion in isolated nerve endings from
      the rat neurohypophysis were studied to determine the relationship between the
      time course of vasopressin secretion and depolarization-induced changes in
      [Ca2+]i. 2. Membrane depolarization by increasing the extracellular [K+] led to
      concentration-dependent, parallel increases in the amount of vasopressin release
      and in peak increases in [Ca2+]i. Half-maximal activation of a change in [Ca2+]i
      was attained at 40 mM extracellular K+. 3. The Ca2+ chelator dimethyl-BAPTA (1,2
      bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid), loaded into the nerve
      endings, reduced K+ depolarization-evoked vasopressin release and efficiently
      antagonized K(+)-induced changes in [Ca2+]i. Moreover, dimethyl-BAPTA
      dramatically reduced basal [Ca2+]i without a reduction in basal secretion. 4. The
      duration of the vasopressin secretory response was similar regardless of applied
      50 mM K+ depolarizations longer than 30 s. The t1/2 of the secretory response was
      45 s. Application of repetitive K+ depolarization pulses repetitive secretory
      responses of similar amplitude and duration. 5. The K(+)-induced changes in
      [Ca2+]i remained elevated throughout the duration of the depolarizing stimulus
      decreasing less than 30% over 3 min. The sustained increase in [Ca2+]i resulted
      largely from continued enhanced Ca2+ influx, demonstrated by susceptibility to
      the dihydropyridine, L-type calcium channel blocker, nicardipine. 6. Vasopressin
      secretion could be reinitiated following its decline to a step K+ depolarization
      by a further step increase in K+ or by removal and readdition of extracellular
      [Ca2+]. Alterations in [Ca2+]i paralleled periods of secretory activity. 7.
      Analysis of secretory responsiveness and change in [Ca2+]i to K+ depolarization
      in medium of altered extracellular [Ca2+] indicates that [Ca2+]i of 20 microM is
      sufficient to trigger vasopressin release. K(+)-induced alterations in [Ca2+]i
      could be observed at [Ca2+]o as low as 5 microM. Although smaller in amplitude to
      that observed at 2.2 mM [Ca2+]o the duration of the K(+)-induced secretory
      response increased at lower [Ca2+]o. 8. Transient vasopressin secretory responses
      were observed to sustained levels of [Ca2+] in digitonin and streptolysin-O
      permeabilized nerve endings. Secretion could be re-evoked, following its decline,
      by a step increase in [Ca2+] or by removal and readdition of [Ca2+]o.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8254514
TI  - The effects of inhibitors of sarcoplasmic reticulum function on the systolic Ca2+
      transient in rat ventricular myocytes.
AB  - 1. The effects of thapsigargin, ryanodine and caffeine were examined on systolic
      Ca2+ transients in indo-1-loaded rat ventricular myocytes. 2. Thapsigargin (1-10
      microM) decreased the magnitude of the Ca2+ transient. This was accompanied by a
      decrease of the rate constant of decay of the transient. 3. Ryanodine (1-10
      microM) decreased the magnitude of the Ca2+ transient. Initially there was no
      change in the rate of decay but further reduction of the magnitude was
      accompanied by a slowing. 4. Caffeine (0.5-10 mM) decreased the magnitude of the
      Ca2+ transient and its rate of decay. These effects were graded with caffeine
      concentration. 5. For a given submaximal reduction of the magnitude of the Ca2+
      transient, the effect on the rate of decay was greatest for thapsigargin, least
      for ryanodine and intermediate for caffeine. 6. The above data are reproduced by
      a model in which all three agents decrease the magnitude of the Ca2+ transient by
      decreasing the calcium content of the sarcoplasmic reticulum (SR) (thapsigargin
      by inhibiting the Ca2+ pump and ryanodine and caffeine by increasing the leak of
      Ca2+ from the SR). The decreased contribution of the SR will thereby slow
      relaxation. The fact that thapsigargin inhibits the SR Ca2+ pump accounts for the
      observation that, for a given decrease of amplitude, it has more effect than the
      other agents on the rate of decay. The difference between caffeine and ryanodine
      is suggested to arise because caffeine potentiates Ca2+ release from the SR and
      thereby attenuates the effect of the decreased SR calcium content on the
      magnitude of the Ca2+ transient.

PMID- 8254515
TI  - Thiamine outflow from the enterocyte: a study using basolateral membrane vesicles
      from rat small intestine.
AB  - 1. Rat small intestinal basolateral membrane vesicles (BLMVs) were prepared and
      found to be 31% non-vesiculated and 69% vesiculated, 4.9% right side out and
      63.8% inside out. 2. Thiamine uptake by BLMVs followed a hyperbolic time course
      reaching equilibrium after 60-90 min incubation. Uptake was not affected by the
      transmembrane potential or by the presence or absence of Na+ or K+ in the
      incubation medium. 3. At concentrations below 1.25 microM, [3H]thiamine was taken
      up mainly by a saturable mechanism with an apparent Michaelis-Menten constant
      (Km) = 1.32 microM and maximal flux (Jmax) = 1.93 pmol (mg protein)-1 (4 s)-1. At
      higher concentrations, a non-saturable mechanism prevailed. 4. Only 29% of
      [3H]thiamine taken up by the vesicles was membrane bound, the remaining being
      translocated into the vesicular space. No thiamine phosphoesters could be
      detected inside the vesicles. 5. In the absence of ATP, the Na(+)-K(+)-ATPase
      inhibitors ouabain, frusemide and vanadate reduced thiamine uptake by 35, 30 and
      15% respectively. 6. In experiments conducted with K+ inside the vesicles and
      Na+, Mg2+ and ATP outside, the time course of thiamine uptake by BLMVs displayed
      an overshoot (80-90% increment) at 30 s incubation as compared to controls. When
      ATP was replaced with phosphocreatine, or when NaCl was replaced with isosmotic
      amounts of KCl, the overshoot disappeared. 7. The thiamine analogues
      pyrithiamine, amprolium and 4'-oxythiamine decreased the ATPase-dependent
      transport of [3H]thiamine by 100, 86 and 31% respectively. 8. These results
      provide evidence that the transport of thiamine by BLMVs is coupled directly to
      the hydrolysis of ATP (primary active transport).

PMID- 8254516
TI  - Ventilatory responses during arm and leg exercise at varying speeds and forces in
      untrained female humans.
AB  - 1. Involvement of neural stimuli, central and/or peripheral in origin, in
      exercise ventilatory control was ascertained by examining the ventilatory
      responses to varying mechanical conditions of arm and leg cycle ergometries.
      Twelve untrained women underwent each of two modes of exercise at three levels of
      loading (0, 5 and 10 N), each at three levels of speed (30, 50 and 72 r.p.m.),
      during which steady-state values of minute ventilation (VE), tidal volume (VT),
      respiratory frequency (f) and CO2 excretion (VCO2) were measured. 2. Using the
      data obtained at the aerobic work intensities, the relationship of ventilatory
      responses (VE, VT and f) to the metabolic (VCO2) and mechanical (speed and load)
      variables were studied by multiple linear regression analysis. Coefficient of
      determination (r2) of the regression model was lowest (0.84) for f in the arm
      exercise and highest (0.99) for VE in the leg exercise. 3. Standardized partial
      regression coefficients of the model indicated that VE response is related to
      VCO2 at the rate of 94 +/- 3% (mean +/- S.E.M.) and to the pedal rate at 8 +/- 3%
      during the leg exercise, while it is closely related to VCO2 in the arm exercise.
      For f response, influence of the rate of limb movement was seen in the leg
      exercise but not in the arm exercise. The different effects of the rate of limb
      movement between the two exercise modes may be related to familiarity with the
      exercise modes, suggesting that a familiarity-related mechanism is involved in
      exercise ventilatory control. 4. A heavier load imposed on the limb muscles
      elicited a greater VT both in the arm and leg exercise and a lower f in the arm
      exercise. Postural control in the upper torso during increased limb muscle
      tension seems to affect VT and f.

PMID- 8254517
TI  - Anomalous permeation of Na+ through a putative K+ channel in rat superior
      cervical ganglion neurones.
AB  - 1. An unanticipated inward tail current was recorded from freshly isolated adult
      rat superior cervical ganglion (SCG) neurones using the whole-cell variant of the
      patch-clamp technique. The tail current was present when Na+ was substituted for
      tetraethylammonium (TEA) as the primary monovalent cation in external solutions
      designed to isolate Ca2+ channel currents (0.5 microM tetrodotoxin present and K+
      omitted). 2. The tail current was observed following step potentials positive to 
      30 mV and reached half-activation near -9.0 mV. The decay of the tail current was
      voltage dependent and could be described with two time constants. Between
      potentials of -120 and -70 mV, tau f, the fast component, varied from 3 to 8 ms
      and tau s, the slow component, changed from 12 to 30 ms, respectively. 3. The
      tail current was not carried by Ca2+, and did not appear to flow through a
      voltage-gated Ca2+ channel or a Ca(2+)-dependent channel as it persisted in the
      absence of external Ca2+ or in the presence of the Ca2+ channel blocker, Cd2+
      (0.1 mM). 4. Varying the external [Cl-] did not alter the reversal potential of
      the tail current indicating that Cl- was not the charge carrier. 5. The reversal
      potential of the tail current changed in accordance with the Nernst relationship
      when [Na+]i/[Na]o was altered. Our results suggested that this 'unusual or
      unanticipated current' (Iu) was carried primarily by Na+. 6. Iu was inhibited by
      the K+ channel-blocking agents quinidine (0.1 mM), external Ba2+ (5 mM) and
      internal Cs+ (145 mM). TEA (20 mM either internally or externally) and
      dendrotoxin (10 microM) were not effective inhibitors of Iu. 7. The decay time
      constants of the tail current and parameters of activation and inactivation of Iu
      were similar to those of TEA-insensitive delayed rectifier-type K+ channel
      currents observed in the presence of 145 mM external K+. 8. Iu was reduced in the
      presence of either external or internal K+. The interaction of external K+ with
      Na+ on the Iu tail amplitude was reminiscent of anomalous mole-fraction
      behaviour. 9. Ion permeability studies revealed that the channel producing Iu had
      a permeability sequence to monovalent cations of 3.5:2.5:2:1:0.5 for Rb+, K+,
      Cs+, Na+ and Li+, respectively. 10. These data suggest that in the absence of
      external K+, the ion selectivity of a TEA-insensitive K+ channel in sympathetic
      neurones is profoundly diminished. Under these conditions, Na+ traversing a K+
      channel can generate an unanticipated inward current.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8254518
TI  - Excitation failure in eccentric contraction-induced injury of mouse soleus
      muscle.
AB  - 1. Histological evidence suggests that the force deficit associated with
      eccentric contraction-induced muscle injury is due to structural damage to
      contractile elements within the muscle fibre. Alternatively, the force deficit
      could be explained by an inability to activate the contractile proteins. It was
      the objective of this study to investigate the latter possibility. 2. Mouse
      soleus muscles were isolated, placed in an oxygenated Krebs-Ringer buffer at 37
      degrees C, and baseline measurements were made. The muscle then performed one of
      three contraction protocols: (1) twenty eccentric (n = 10 muscles); (2) ten
      eccentric (n = 12); or (3) twenty isometric (n = 10) contractions. At the end of
      the injury protocol, measurements were made during performance of a passive
      stretch, twitch and tetanus. Next, force was recorded during exposure of the
      muscle to buffer containing 50 mM caffeine. 3. Decrements in maximal isometric
      tetanic force (P0) observed for muscles in the twenty eccentric, ten eccentric,
      and twenty isometric contraction protocols were 42.6 +/- 4.2, 20.0 +/- 2.3 and
      3.9 +/- 2.4%, respectively. However, the caffeine-elicited forces in muscles from
      the three protocols were not different when corrected for initial differences in
      P0 (64.9 +/- 1.3, 64.2 +/- 2.1 and 68.9 +/- 2.5% of pre-injury P0). The peak
      caffeine-elicited force was 118.4 +/- 8.6% of post-injury P0 for the muscles in
      the twenty eccentric contraction protocol, which was significantly different from
      that observed for the other protocols (71.8-80.2% post-injury P0). These findings
      indicate that the force deficit in this muscle injury model results from a
      failure of the excitation process at some step prior to calcium (Ca2+) release by
      the sarcoplasmic reticulum. 4. In an attempt to locate the site of failure,
      intracellular measurements were made in injured muscles to test whether injury to
      the sarcolemma might have resulted in a shift of the resting membrane potential
      of the muscle fibre. However, microelectrode measurements of resting membrane
      potential for muscles in the twenty eccentric contraction protocol (-74.4 +/- 0.6
      mV) were not different from muscles in the twenty isometric contraction protocol
      (-73.4 +/- 1.0 mV). These data suggest that membrane resting conductances were
      normal and are compatible with the idea that the ability of the injured fibres to
      conduct action potentials was probably not impaired.

PMID- 8254519
TI  - Effect of bradykinin on respiratory rate in anaesthetized rabbits; role of
      rapidly adapting receptors.
AB  - 1. This study was performed in anaesthetized, spontaneously breathing rabbits:
      (a) to determine the effect of bradykinin administered into the right atrium on
      the respiratory rate, and (b) to elucidate the potential role of rapidly adapting
      receptors (RARs) in mediating this effect. The role of RARs was established by
      graded cooling of the cervical vagi. The respiratory rate was measured from an
      intrapleural pressure tracing. 2. Dose-response curves relating right atrial
      injections of bradykinin (0.25, 0.5, 1.0 and 1.5 micrograms/kg) to the
      respiratory rate were established in the control state (i.e. vagi at 37 degrees
      C). The respiratory rate increased significantly (P < 0.01, ANOVA) from a control
      value of 51.3 +/- 6.8 breaths/min by 12 +/- 3, 25 +/- 5, 43 +/- 7 and 58 +/- 11%
      respectively. At doses of 1.0 and 1.5 micrograms/kg I.V., the increase in rate
      was preceded by apnoea. 3. The dose-response curves were repeated with bolus
      injections of bradykinin (0.25, 0.5, 1.0 and 1.5 micrograms/kg) after cooling the
      cervical vagi to 8-9 degrees C. The increase in respiratory rate was attenuated
      significantly (P < 0.01 ANOVA). The rate increased from a control value of 27.2
      +/- 2.1 breaths/min by 5 +/- 2, 6 +/- 2, 16 +/- 5 and 21 +/- 8% respectively.
      With vagi cooled, apnoea was increased in duration and occurred at lower doses.
      On rewarming vagi, the original responses were reestablished. 4. When the study
      was repeated after bilateral vagotomy, apnoea was abolished but there was a small
      residual increase in rate. This increase was similar to that seen after cooling
      the vagi (P > 0.05). 5. RAR (n = 5) activity was recorded from the cervical
      vagus. Right atrial injections of bradykinin (0.25-1.0 micrograms/kg) stimulated
      RARs. On cooling the vagi to 8-9 degrees C caudal to the recording site, the
      increase in activity was blocked. 6. These data support the proposition that
      bradykinin increases the respiratory rate in rabbits and that this response is,
      in part, a reflex mediated by RARs. In addition, bradykinin has other secondary
      effects on respiration: an aponea which is mediated by non-myelinated vagal
      afferents and a small stimulatory effect on respiration which persists after
      bilateral vagotomy.

PMID- 8254520
TI  - Adrenal cortical and medullary responses to acetylcholine and vasoactive
      intestinal peptide in conscious calves.
AB  - 1. Adrenal responses to intra-aortic infusions of acetylcholine and vasoactive
      intestinal peptide (VIP) have been investigated in functionally hypophysectomized
      calves given exogenous adrenocorticotrophic hormone (ACTH, 2 ng min-1 kg-1 I.V.).
      2. Infusions of VIP at a dose of 0.13 micrograms min-1 kg-1 caused a small, but
      significant increase in adrenaline and noradrenaline output which was, however,
      far below the level recorded previously in response to acetylcholine (0.7
      micrograms min-1 kg-1). In contrast, these doses of the two agonists produced
      closely similar rises in adrenal cortisol output. 3. The steroidogenic effects of
      acetylcholine and VIP were found to be strictly additive and no evidence of
      potentiation was obtained in relation to either cortical or medullary responses
      or in the case of any of the cardiovascular responses which were monitored. 4.
      Intra-aortic infusions of VIP, at a dose which produced a substantial increase in
      adrenal steroidogenesis (0.065 micrograms min-1 kg-1), had no effect on the
      output of catecholamines, enkephalin-like immunoreactivity or corticotrophin
      releasing factor, either in the presence or absence of acetylcholine. 5. It is
      concluded that VIP is unlikely to modulate adrenal medullary responses to
      muscarinic stimulation in this species as it has been claimed to do in the rat
      and does not potentiate adrenal steroidogenesis in response to acetylcholine as
      it does to ACTH.

PMID- 8254521
TI  - The neuropeptide CRF is involved in the modulation of the baroreflex during
      hindlimb ischaemia in the anaesthetized rat.
AB  - 1. The effects of bilateral hindlimb ischaemia (BHLI), and of administration of
      the neuropeptide corticotrophin-releasing factor (CRF), were tested on
      cardiovascular variables in propofol-anaesthetized Sprague-Dawley rats. In
      addition, the effects of antagonizing endogenous CRF on the cardiovascular
      response to BHLI was investigated. 2. BHLI produced significant increases in mean
      arterial pressure and heart rate. Baroreflex sensitivity was reduced in all
      animals tested both 10 and 30 min after the induction of ischemia and this was
      accompanied by changes which are consistent with an underlying baroreflex
      resetting. 3. Intracerebroventricular (I.C.V.) administration of CRF (1.5 nmol)
      produced significant increases in heart rate but not mean arterial pressure. CRF
      also produced significant reductions in baroreflex sensitivity 10 and 30 min
      after administration, but there was no consistent evidence of baroreflex
      resetting. These effects of CRF could be prevented by pretreatment with the
      synthetic CRF antagonist, alpha-helical CRF(9-41) (alpha hCRF, 6.5 nmol, I.C.V.),
      which itself had no effect on these cardiovascular variables. 4. Pretreatment
      with alpha hCRF (6.5 nmol, I.C.V.) prevented the reduction in baroreflex
      sensitivity observed 10 min after the induction of BHLI, but had no consistent
      effect on the pressor or tachycardiac responses to BHLI and allowed a clear
      expression of BHLI-induced baroreflex resetting. alpha-Helical CRF(9-41) had no
      effect on the reduction in baroreflex sensitivity after 30 min of BHLI. 5. We
      conclude that corticotrophin-releasing factor mediates, at least in part, the
      early reduction in baroreflex sensitivity observed during hindlimb ischaemia in
      the rat.

PMID- 8254522
TI  - Calcium entry through nicotinic receptor channels and calcium channels in
      cultured rat superior cervical ganglion cells.
AB  - 1. Patch-clamp techniques in conjunction with indo-1 fluorescent measurements
      were used to measure increases in intracellular free calcium concentration and
      membrane conductance induced by the activation of nicotinic and calcium channels
      in cultured rat sympathetic neurons. 2. Under voltage-clamp conditions, pressure
      application of the nicotinic agonist DMPP (1,1-dimethyl-4-phenylpiperazinium
      iodide, 100 microM, 100 ms) increased [Ca2+]i by 193 +/- 26 nM at a clamp
      potential of -60 mV. This was accompanied by an inward current of -4.53 +/- 0.89
      nA, giving a mean ratio of the delta (Ca2+]i to the total inward charge transfer
      of 42.7 nmoles per litre of free calcium per nanocoulomb of charge (M/q ratio).
      3. The DMPP-induced current and associated delta [Ca2+]i were reduced by
      mecamylamine (100 nM-10 microM) but were unaffected by alpha-bungarotoxin (100
      nM) or cadmium (100 microM). 4. The M/q ratio was not affected by the holding
      potential (from -80 to -40 mV) but was a function of the external calcium
      concentration. 5. The M/q ratio was reduced by increasing the intracellular
      calcium buffering capacity and increased by heparin but not affected by ryanodine
      or by depletion of the caffeine-sensitive calcium store. 6. Under the same
      recording conditions, we quantified the increase in [Ca2+]i associated with
      activation of the voltage-dependent calcium current. On average at -60 mV, the
      M/q ratio of this highly calcium-selective permeability was 1961 mM nC-1, which
      is 46 times that obtained for the nicotinic channel. 7. Assuming constant-field
      theory, ion-substitution experiments suggest that in 2.5 mM external calcium, the
      permeability sequence for the nicotinic conductance was Cs+ < Li+ < Na+ < K+ <
      Ca2+. 8. We conclude that the nicotinic channels in rat sympathetic neurones are
      significantly permeant to Ca2+ and that the influx of Ca2+ through these channels
      is the principal cause of the rise in [Ca2+]i seen under voltage clamp.

PMID- 8254523
TI  - Changes in crossbridge and non-crossbridge energetics during moderate fatigue of
      frog muscle fibres.
AB  - 1. The effect of sarcomere length (SL) during a fatiguing series of isometric
      tetani of frog muscle fibres was investigated. Tetani at 2.3 microns SL were more
      fatiguing than tetani at 3.2 microns SL, in that force declined twice as much as
      relaxation became much slower. 2. In a second set of experiments the force and
      heat production were measured during a series of fatiguing tetani. Heat was
      separated into two components: (a) crossbridge heat which is dependent on
      filament overlap and interaction, and (b) non-crossbridge heat which is
      independent of filament overlap and due to Ca2+ turnover. 3. In a series of fifty
      tetani, force, crossbridge heat and non-crossbridge heat each declined by 25-30%
      of its initial value. 4. The 25% reduction in non-crossbridge heat occurred
      completely during the first few tetani of the fatiguing series while force
      declined by less than 3%. This may be due to a reduction in Ca2+ binding to
      parvalbumin and to Ca2+ remaining bound during the remainder of the fatigue
      series. 5. After the first few tetani of the fatigue series the non-crossbridge
      heat hardly changed as force declined by a further 25% of its initial value.
      Continuing reduction of force with constant Ca2+ turnover indicates a reduction
      in the Ca2+ sensitivity of the filaments, and/or a reduction in the average force
      per attached crossbridge. 6. At the start of the fatiguing series, as force
      declines by about 7.5% there is a much larger decline of crossbridge heat (17%).
      The reason for this is unknown. Later in the series, force declined more rapidly
      than heat. This is probably due to a progressive accumulation of inorganic
      phosphate which acts by depressing force more than it depresses ATP breakdown.

PMID- 8254524
TI  - Splenic control of intravascular volume in the rat.
AB  - 1. We tested the hypothesis that hypervolaemia causes an increase in intrasplenic
      filtration of cell-free fluid out of the vasculature. To this end we developed a
      preparation in the anaesthetized rat whereby the splenic vein could be non
      occlusively cannulated. 2. Haematocrit and plasma protein concentrations were
      measured in the splenic afferent and efferent blood supplies. 3. In response to
      volume loading with saline (1% body weight), there was a sustained increase in
      the arterial-venous differential of haematocrit, i.e. there was a relative
      increase in the haematocrit of the blood draining from the spleen. There was no
      such change in plasma protein concentration. By contrast, this degree of volume
      loading had no effect on the haematocrit of blood passing through the
      hindquarters of the animal. 4. Following volume expansion, there was no
      significant difference in the protein concentration of the plasma and the lymph
      fluid collected from the splenic lymphatic duct. 5. Distension of the superior
      vena caval-right atrial junction by means of a small inflatable balloon, caused a
      similar increase in the splenic venous haematocrit, and again, no change in
      plasma protein concentration. 6. We interpret these results to mean that, in
      response to expansion of the intravascular space, there is increased intrasplenic
      filtration of plasma out of the blood and into the lymphatic system.

PMID- 8254525
TI  - Nicotinic agonists antagonize quantal size increases and evoked release at frog
      neuromuscular junction.
AB  - 1. Previous studies at the frog neuromuscular junction showed that quantal size
      can be increased two- to fourfold by a variety of treatments, including prior
      exposure to hypertonic solution (which activates protein kinase A) and insulin
      (which acts via an unknown pathway). Size increases largely because quanta
      contain more acetylcholine (ACh). 2. Now the effects of cholinergic agonists on
      the increases in quantal size have been studied. One muscle from a frog was kept
      for 2 h in hypertonic sodium gluconate solution. The miniature endplate potential
      (MEPP) sizes were measured in saline: they had increased about fourfold. The
      paired muscle went through the same experimental sequence, except that an agonist
      was added to the hypertonic gluconate solution. Again MEPP sizes were measured in
      saline. The increase in quantal size was significantly depressed by 0.2 microM
      1,1-dimethyl-4-phenyl- piperazinium (DMPP). The sequence of effectiveness of
      agonists was: DMPP > carbachol > or = ACh = cytisine > oxytremorine. This
      sequence suggests that the receptor belongs in the nicotinic class. 3. Quantal
      size is doubled after 1 h in insulin. One micromolar carbachol largely blocked
      the size increase. 4. The effects of cholinergic antagonists were tested by
      keeping the experimental muscle in hypertonic gluconate solution containing 1
      microM carbachol plus an antagonist. The controls were paired muscles kept in
      hypertonic gluconate solution (without carbachol or antagonist). MEPP sizes were
      measured in saline. The depressing action of carbachol on the increase in MEPP
      size was blocked by 0.2 microM neuronal-bungarotoxin (nBTX). The sequence of
      effectiveness of antagonists was: nBTX > trimethaphan > d-tubocurarine (dTC). Ten
      micromolar atropine (without carbachol) depressed the increase in quantal size.
      Therefore, the antagonist potency of atropine could not be adequately tested.
      Carbachol action was not blocked by 10 microM hexamethonium or 10 microM
      mecamylamine. 5. Once quanta are made large they can be converted back to normal
      size by cholinergic agonists. Muscles in which quantal size had been enlarged
      were exposed to hypertonic solutions containing the agonist. Quantal size was
      reduced to a fraction of its former value when the hypertonic solution contained
      1 microM carbachol- or 1 microM DMPP. One micromolar oxytremorine had no effect.
      Carbachol still reduced quantal size when applied in low-Ca2+ solutions, so it
      does not appear to act by elevating intracellular [Ca2+]. 6. Previous work
      suggested that the treatments produce a subpopulation of large quanta that are
      positioned for release.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254526
TI  - Extracellular fluid translocation in perfused rabbit atria: implication in
      control of atrial natriuretic peptide secretion.
AB  - 1. Transmural transport of 22Na+, 51Cr-EDTA, [3H]inulin and [14C]Dextran (57 kDa)
      was measured in perfused rabbit atria. The radiolabelled extracellular space
      (ECS) markers and [14C]Dextran were introduced into the pericardial space or
      atrial lumen. Atrial volume changes were induced by steps up and down in atrial
      pressure. 2. Basal rates of transmural transport of radiolabelled ECS markers
      across the atrial wall were relatively stable up to 70 min. Atrial stretch and
      release resulted in a rapid but transient, and reversible increase in the ECS
      fluid (ECF) translocation. The increased translocation of the ECF into the atrial
      lumen occurred within 15 s of the reduction of atrial distension and returned to
      the baseline level within 60 s. 3. Transmural transport of [3H]inulin across the
      atrial wall was bidirectional. 4. The clearance of radiolabelled ECS markers was
      molecular-size dependent. The transmural clearance of [3H]inulin was dependent on
      the distension-reduction volume changes induced by atrial stretch and release.
      Little transport of [14C]Dextran across the atrial wall was observed. 5. The ECF
      translocation across the atrial wall was not influenced by changes in external
      Ca2+ but was suppressed by low temperature. 6. Dynamic changes in the ECS of the
      atrium were observed in response to atrial distension and reduction. The ECS of
      the atrium increased on distension and decreased on reduction of atrial
      distension. 7. Reduction in atrial distension resulted in an increase in the
      secretion of immunoreactive atrial natriuretic peptide (ANP) which coincided with
      an increase in the translocation of the ECF. The secretion of immunoreactive ANP
      was a function of the translocation of the ECF. 8. It is suggested that atrial
      stretch and release may play a role in driving fluid flow within the interstitium
      and fluid translocation out of the interstitium. This fluid movement presumably
      leads to convective transport of released ANP into the atrial lumen.

PMID- 8254527
TI  - Response of sensory units with unmyelinated fibres to mechanical, thermal and
      chemical stimulation of the cat's cornea.
AB  - 1. In the cat anaesthetized with sodium pentobarbitone, electrical activity was
      recorded from single unmyelinated sensory fibres innervating the cornea. 2. Based
      on their response to mechanical (calibrated aesthesiometer), chemical (10 mM
      acetic acid or 616 mM NaCl) and thermal (cooling from 35 to 5 degrees C; heating
      to 51 degrees C) stimuli, corneal unmyelinated fibres were classified as
      polymodal (71%) or 'cold' nociceptors (29%). 3. Polymodal units responded to
      mechanical indentation of the cornea and developed fatigue after repeated
      stimulation. They were excited by temperatures over 37 degrees C and exhibited
      sensitization to repeated heating. 4. Corneal polymodal units were also activated
      by topical application of 10 mM acetic acid and hypertonic NaCl (616 mM).
      Capsaicin (0.33 mM) elicited a discharge of impulses that was followed by
      inactivation to mechanical, chemical and thermal stimuli. 5. 'Cold' nociceptors
      had small receptive fields, preferentially located at the periphery of the
      cornea. They were excited by small temperature decreases of the corneal surface
      in a range between 30 and 8 degrees C, but were not responsive to noxious heat.
      6. 'Cold' nociceptors encoded temperature changes between 35 and 23 degrees C.
      The discharge was proportional to the velocity of the temperature drop; sustained
      temperatures were not signalled by changes in static frequency values. 'Cold'
      nociceptive fibres responded to hypertonic NaCl (616 mM) and weakly to 10 mM
      acetic acid. Capsaicin (0.33 mM) first excited and then inactivated 'cold'
      nociceptors. 7. Thermoreceptive fibres were found in the episclera. They fired in
      bursts and responded to small temperature decreases, but were insensitive to
      irritant chemical and capsaicin.

PMID- 8254528
TI  - Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity.
AB  - 1. In healthy humans during aerobic exercise ventilation increases and mean
      arterial PCO2 usually remains constant over a wide range of CO2 production. 2.
      Congenital central hypoventilation syndrome (CCHS) is associated with ineffective
      chemoreceptor regulation of breathing and severe hypoventilation during sleep
      (requiring mechanical ventilation) reflecting abnormalities in the brainstem
      respiratory complex or its chemoreceptor input. Such patients can have adequate
      spontaneous ventilation during resting wakefulness and participate in normal
      activities. 3. If children with CCHS have normal ventilatory responses to
      exercise then chemoreceptors are not necessary for this ventilatory response or
      the resultant control of Pa,CO2 during exercise. We studied five children with
      CCHS (aged 8-17 years) with abnormally low ventilatory responses to steady-state
      increased end-tidal PCO2 (< 9 ml min-1 kg-1 mmHg-1) and five age-matched
      controls. 4. Depth and rate of breathing, end-tidal PCO2, end-tidal PO2, CO2
      production, O2 utilization and heart rate were monitored during the following
      conditions: whilst subjects stood at rest; following the onset of treadmill
      exercise (4 m.p.h.); during steady-state exercise (4 m.p.h.); during an
      incremental maximal exercise test; and during recovery from exercise. 5. There
      were no significant differences in the ventilatory responses between CCHS
      subjects and controls during the onset of treadmill exercise, in the dynamic
      response in achieving the steady-state exercise, during steady-state exercise, in
      the recovery from steady-state exercise, or during incremental exercise (up to
      the point of presumed blood lactate accumulation, as indicated by gas exchange
      criteria). There was a very small mean increase in PCO2 in both groups during
      steady-state exercise (controls 1.4 mmHg; CCHS 2.2 mmHg). 6. The only differences
      which emerged between groups were (i) slightly more variability in PCO2 in the
      CCHS group during steady-state exercise, and (ii) the CCHS subjects did not
      hyperventilate, as the controls did, at exercise levels above the point of
      presumed blood lactate accumulation. 7. Breath-by-breath coefficient of variation
      of ventilation was significantly reduced in both groups during steady-state
      exercise compared to rest. There were no differences between groups in either
      state. 8. We conclude that chemoreceptors are not necessary for an appropriate
      ventilatory response to aerobic exercise. Hence, other stimuli, such as afferent
      information from the exercising limbs or signals related to activation of the
      motor cortex, can increase alveolar ventilation in close proportion to CO2
      production. 9. The lack of hyperventilatory response to blood lactate
      accumulation during heavy exercise provides good evidence that these CCHS
      patients have ineffective peripheral chemoreception.

PMID- 8254529
TI  - [Ca2+]i transients and [Ca2+]i-dependent chloride current in single Purkinje
      cells from rabbit heart.
AB  - 1. Single Purkinje cells, enzymatically isolated from rabbit ventricle, were
      studied under whole-cell voltage clamp and internally perfused with the
      fluorescent Ca2+ indicator, indo-1 (100 microM). 2. Fast [Ca2+]i transients were
      elicited by brief depolarizations from a holding voltage of -45 mV and by
      repolarization from very positive potentials. The peak [Ca2+]i-voltage relation
      was bell-shaped with a peak around +10 mV. 3. [Ca2+]i transients were completely
      blocked by the Ca2+ channel antagonist, nisoldipine (10 microM) and were very
      small when Ca2+ release from the sarcoplasmic reticulum (SR) was prevented by
      superfusion of cells by caffeine (1 mM) or ryanodine (10 microM). A fast
      application of caffeine induced a transient increase in [Ca2+]i. These results
      suggest [Ca2+]i transients are due to Ca(2+)-induced Ca2+ release from the SR. 4.
      Rate of decline of the [Ca2+]i transient was voltage dependent, suggesting
      contribution of the Na(+)-Ca2+ exchanger to Ca2+ efflux. At very positive
      potentials (> +60 mV), Ca2+ influx through the Na(+)-Ca2+ exchanger could be
      observed. 5. A transient outward current was observed at potentials positive to
      +10 mV, but only if depolarizing pulses were accompanied by a [Ca2+]i transient.
      6. When the amplitude of the [Ca2+]i transient was changed by (1) changes in
      [Ca2+]o, (2) changes in frequency of depolarization or (3) conditioning
      prepulses, the amplitude of the outward current changed in the same direction.
      This suggests activation of the current is dependent on and graded by [Ca2+]i. 7.
      The outward current was observed in K(+)-free solutions, in the presence of Cs+
      and TEA+, and was not blocked by 4-aminopyridine (10 mM). In contrast, DIDS (100
      microM) decreased the outward current by 70 +/- 20% (mean +/- S.D., n = 9),
      without affecting [Ca2+]i. 8. When external Cl- was lowered, the amplitude of the
      outward current decreased; when internal Cl- was replaced by aspartate, it became
      apparent at more negative potentials. These interventions strongly suggest the
      current was carried by Cl-; it can therefore be referred to as a [Ca2+]i
      activated Cl- current or ICl(Ca). 9. When ICl(Ca) was maximally activated during
      a conditioning step, steps to negative potentials revealed inward currents
      through ICl(Ca) (in symmetrical Cl- solutions). The fully activated I-V relation
      was linear. 10. ICl(Ca) could be activated at membrane potentials between -80 and
      +80 mV by a fast application of caffeine (10 mM), inducing Ca2+ release from the
      SR, demonstrating that ICl(Ca) does not require membrane depolarization or Ca2+
      influx through the Ca2+ channel for its activation.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8254530
TI  - Mechanisms of oscillatory activity in guinea-pig nucleus reticularis thalami in
      vitro: a mammalian pacemaker.
AB  - 1. The ionic mechanisms of rhythmic burst firing and single spike, tonic
      discharge were investigated with extracellular and intracellular recordings of
      single neurones in the guinea-pig nucleus reticularis thalami (NRT) maintained as
      a slice in vitro. 2. Activation of cortical/thalamic afferents to NRT neurones
      resulted in a short latency burst of action potentials which could be followed by
      a rhythmic sequence of oscillatory burst firing. Intracellularly, this
      oscillatory activity was associated with an alternating sequence of low threshold
      Ca2+ spikes separated by after-hyperpolarizing potentials. Intracellular
      injection of short duration hyperpolarizing current pulses resulted in a similar
      sequence of oscillatory burst firing, suggesting that this activity is an
      intrinsic property of NRT cells. The frequency of rhythmic burst firing was
      highly voltage and temperature dependent and was between 7-12 Hz at -65 to -60 mV
      at 38 degrees C. In addition, at depolarized membrane potentials, oscillatory
      burst firing was typically followed by a prolonged tail of single spike activity.
      3. Application of the Na+ channel poison tetrodotoxin blocked the generation of
      fast action potentials, but left intact the rhythmic sequence of low threshold
      Ca2+ spikes separated by after-hyperpolarizing potentials (AHPs). The reversal
      potential of the AHPs was -94 mV, suggesting that it was mediated by an increase
      in K+ conductance. Extracellular application of tetraethylammonium or apamin, or
      intracellular injection of Cs+ or the Ca2+ chelating agent EGTA, blocked the Ca2+
      spike AHP, indicating that it is mediated by a Ca(2+)-activated K+ current. 4.
      Block of the AHP resulted in the marked enhancement of a slow after-depolarizing
      potential (ADP). The slow ADP occurred only following the generation of low
      threshold Ca2+ spikes. Replacement of extracellular Ca2+ with Mg2+ or Sr2+
      resulted in an abolition of the slow ADP. In addition, the increase in [Mg2+]o
      resulted in an abolition of the low threshold Ca2+ spike. In contrast,
      replacement of extracellular Ca2+ with Ba2+ did not abolish the slow ADP. These
      results indicate that the ADP can be activated by either Ca2+ or Ba2+, but not by
      Mg2+ or Sr2+. 5. Replacement of extracellular Na+ with choline+ did not abolish
      the slow ADP, while replacement with N-methyl-D-glucamine+ did, indicating that
      the slow ADP can be supported by choline+, but not by N-methyl-D-glucamine+.
      Neither chemical affected the low threshold Ca2+ spike. These results are
      consistent with the slow ADP being mediated by a Ca(2+)-activated non-selective
      cation (CAN) current.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254532
TI  - The contribution of [Ca2+]i to the slowing of relaxation in fatigued single
      fibres from mouse skeletal muscle.
AB  - 1. The contribution of Ca2+ vs. cross-bridges to the slowing of relaxation in
      fatigue was studied in intact, single fibres dissected from a mouse foot muscle.
      Fatigue was produced by repeated 350 ms tetani. The free myoplasmic Ca2+
      concentration ([Ca2+]i) was measured with indo-1. 2. The rate of [Ca2+]i decline
      after a tetanus was reduced in fatigue but this reduction appeared smaller than
      the decrease in relaxation speed. 3. Under control conditions, steady-state
      [Ca2+]i-tension curves were constructed from measurements of tetani at various
      stimulus frequencies. Measurements from the final part of fatigue runs, where
      both tetanic [Ca2+]i and tension fell relatively fast, were used to construct
      similar curves in fatigue. A comparison of these curves revealed a reduction of
      both the maximum Ca(2+)-activated tension and the myofibrillar Ca2+ sensitivity
      in fatigue. 4. Calcium-derived tension records were generated by converting
      [Ca2+]i signals during tetani into tension by means of the steady-state [Ca2+]i
      tension relation. These records would represent a situation where tension
      responds to changes of [Ca2+]i without delays due to, for instance, cross-bridge
      attachment or detachment. The relaxation speed of the calcium-derived tension was
      similar in control and fatigue; the lag between the calcium-derived and the real
      tension was about twice as long in fatigue. 5. Both the decline of [Ca2+]i and
      tension were markedly faster after a 10 s pause elicited during fatigue runs at
      the time of maximum slowing of relaxation. The relaxation of the calcium-derived
      tension was also faster after the pause. 6. The function of the sarcoplasmic
      reticulum (SR) Ca2+ pumps was analysed by plotting the rate of [Ca2+]i decline
      vs. [Ca2+]i during the tail of elevated [Ca2+]i after tetani. This analysis
      showed approximately a sevenfold reduction of the pump rate in fatigue. 7. In
      conclusion, the rate of [Ca2+]i decline after a tetanus is reduced in fatigue
      probably due to impaired SR Ca2+ pumping. This is not the cause of the slowed
      relaxation because it is counteracted by a reduced myofibrillar Ca2+ sensitivity.
      Thus, the slowing of relaxation in fatigued mouse muscle fibres would reflect
      slowed cross-bridge kinetics.

PMID- 8254531
TI  - Unidirectional interaction between two intracellular calcium stores in rat
      phaeochromocytoma (PC12) cells.
AB  - 1. A clone of the rat phaeochromocytoma cell line (PC12) was treated with nerve
      growth factor (NGF) for 4-6 days and used to study caffeine- and bradykinin
      induced Ca2+ release from intracellular Ca2+ stores. The caffeine-sensitive store
      can be depleted by Ca(2+)-induced Ca2+ release (CICR), while the bradykinin
      induced release is mediated by inositol 1,4,5-trisphosphate (IP3). The effect of
      Ca2+ release from these Ca2+ stores on cytosolic free Ca2+ ([Ca2+]i) was measured
      by means of fura-2 single cell microfluorimetry. 2. Caffeine application caused
      no or only a small Ca2+ release in untreated cells in normal culture medium. The
      caffeine-sensitive pool could be filled by Ca2+ entry into cells through either
      voltage-activated Ca2+ channels or ligand-gated cation channels. 3. Bradykinin
      application produced substantial Ca2+ release in untreated cells in normal
      culture medium. The response was enhanced after K(+)-depolarization of the cells.
      The bradykinin-induced release of Ca2+ also caused depletion of the caffeine
      sensitive pool by CICR. However, Ca2+ released from the IP3-sensitive store was
      not sequestered into the caffeine-sensitive Ca2+ store. 4. The caffeine-induced
      rise in [Ca2+]i was blocked by ryanodine in a use-dependent manner. In addition,
      a substantial use-dependent ryanodine block resulted from the bradykinin-induced
      rise of [Ca2+]i and subsequent CICR. By contrast, the K(+)-induced rise of
      [Ca2+]i caused only a marginal use-dependent ryanodine inhibition of Ca2+
      release. 5. Our results suggest an enhancement of the IP3-induced [Ca2+]i rise in
      the cytoplasm by CICR from the caffeine-sensitive pool. 6. A mathematical model
      adequately simulates our experimental data.

PMID- 8254533
TI  - The nature of the decrease in blood-cerebrospinal fluid barrier exchange during
      postnatal brain development in the rat.
AB  - 1. The blood-cerebrospinal fluid (CSF) exchange of a wide range of passively
      transported lipid insoluble compounds (0.43-5.4 nm molecular radius) has been
      investigated in rats at different stages of postnatal development (2 days old to
      adult). A novel 'litter-based' model for investigating blood-CSF barrier exchange
      in immature animals is described. 2. At each age investigated there was a clear
      inverse correlation between molecular radius and blood-CSF barrier exchange, in
      addition to an overall decrease in blood-CSF barrier exchange with increasing
      age. 3. The decrease in blood-CSF barrier exchange with age was not consistent
      with a reduction in pore diameters, nor does it appear to be due to an increase
      in the CSF sink effect with age. It seems likely to be due to a relative decrease
      in the number of a population of large diameter pores.

PMID- 8254534
TI  - Mercury blockage of apical water channels in toad skin (Bufo marinus).
AB  - 1. Net water flow (Jw) was continuously monitored across the abdominal skin of
      the toad Bufo marinus by means of a volumetric, automatic technique. Jw was
      either averaged over periods of 2 min or taken cumulatively (10 or 30 min
      periods). 2. The state of high water permeability induced by vasopressin or
      isoprenaline was reversed (88-89% inhibition of delta Jw after 1 h) by the
      addition of 10(-3) M HgCl2 (or CH3ClHg) to the external bathing medium.
      Similarly, pre-exposure of the skins to Hg2+, totally blocked the induction of
      the hydrosmotic response to the same agents. By itself, Hg2+ exerted only a minor
      (26%) stimulation of basal Jw. 3. There was a sigmoidal dose-response
      relationship between the reduction of the hydrosmotic effect of vasopressin (VP)
      and the concentration of Hg2+ in the external medium, with a half-maximal effect
      at 1.2 x 10(-4) M HgCl2. 4. Total replacement of Na+ by K+, Rb+ or Cs+ in the
      Ringer solution, caused a VP-like, hydrosmotic effect that was reversed, or
      prevented, by exposure to Hg2+ in a manner indistinguishable from that previously
      seen with vasopressin or isoprenaline. 5. The data point to the presence of a
      Hg(2+)-sensitive apical water pathway in stimulated epithelia, very probably
      constituted by water channels similar to those reported in red blood cells,
      amphibian bladder and mammalian kidney tubules.

PMID- 8254535
TI  - N-ethylmaleimide discriminates between two lysine transport systems in human
      erythrocytes.
AB  - 1. The sulfhydryl reagent N-ethylmaleimide (NEM) was shown to inactivate the low
      affinity lysine transporter in human erythrocytes (system y+) without affecting
      the high affinity transporter (system y+L). 2. Pre-treatment of the cells with
      NEM reduced the rate of entry of L-[14C]lysine (1 microM) by approximately 50%
      (maximum effect). 3. NEM (0.2 mM) inhibited the NEM-sensitive component of the
      flux with mono-exponential kinetics. The inactivation rate constant (k, +/-
      S.E.M.) was 0.53 +/- 0.027 min-1 (25 degrees C). The substrate did not protect
      against inactivation. 4. Lysine self-inhibition experiments revealed two
      transport systems in untreated cells (half-saturation constants Km; +/- S.E.M.),
      12.0 +/- 1.7 microM and 109 +/- 15.6 microM) and only one high affinity system in
      NEM-treated cells (Km 9.5 +/- 0.67 microM), indicating that NEM inactivates
      system y+. 5. The NEM-insensitive L-[14C]lysine influx (system y+L) was inhibited
      with high affinity by unlabelled neutral amino acids. The inhibition constant for
      L-leucine in sodium medium (Ki +/- S.E.M.) was 10.7 +/- 0.72 microM (37 degrees
      C). The system was also strongly inhibited by L-methionine, L-glutamine and with
      less affinity by L-phenylalanine and L-serine. N-methyl-L-leucine, L-proline and
      2-amino-2-norbornane-carboxylic acid, a bicyclic analogue of leucine, did not
      exert a significant effect. 6. Lysine transport through system y+L occurred at
      the same rate in Na+, K+ or Li+ medium and the binding of lysine to the
      transporter was unaffected by Na+ replacement. 7. The interaction of system y+L
      with neutral amino acids was dependent on the cation present in the medium. The
      inhibition constant for leucine and glutamine increased approximately 90- and 60
      fold respectively when Na+ was replaced by K+. Li+ was shown to be a very good
      substitute for Na+.

PMID- 8254536
TI  - Ionic mechanisms of action potential prolongation at low temperature in guinea
      pig ventricular myocytes.
AB  - 1. We studied the effects of low temperature on the action potentials and
      membrane currents of guinea-pig ventricular myocytes, using a tight-seal whole
      cell clamp technique. 2. The action potential duration at 95% repolarization was
      prolonged from 146 +/- 33 ms (mean +/- S.D., n = 6) at 33-34 degrees C (control
      temperature) to 314 +/- 83 ms at 24-25 degrees C (low temperature). 3. In whole
      cell clamp experiments, low temperature decreased the calcium current (ICa), the
      delayed rectifier potassium current (IK), and the inwardly rectifying potassium
      current (IK1) with 'apparent' Q10 (temperature coefficient) values of 2.3 +/- 0.6
      for ICa, 4.4 +/- 1.2 for IK tail current and 1.5 +/- 0.3 for IK1 (n = 7). 4. The
      effect of low temperature on IK was further studied in the presence of 0.6 microM
      nicardipine to block ICa. The decay phase of the IK tail consisted of two
      exponential components. The fast but not the slow component was highly sensitive
      to the temperature change with an apparent Q10 of 4.5. 5. We found that a
      component of time-independent current is also sensitive to the temperature. The
      current had a linear I-V relationship and remained almost unchanged after
      inhibition of Na(+) -K+ pump in K(+)-free external solution. 6. Using our
      mathematical model of the ventricular action potential (a modification from the
      DiFrancesco-Noble model), we simulated the action potential at low temperature by
      modifying some of the membrane currents, namely IK, IK1, ICa and a component of
      background current. It was shown that simultaneous changes in these currents
      could reproduce approximately 75% of the action prolongation induced by low
      temperature.

PMID- 8254537
TI  - Conversion of a fixed partial denture to an interim removable partial denture: a
      clinical report.
AB  - An easy, one-appointment procedure for the modification and conversion of a
      failed 10-unit FPD into a complete interim overdenture has been described. The
      benefits to the patient and advantages to the dentist have been noted.

PMID- 8254538
TI  - Porcelain adherence to high-palladium alloys.
AB  - The adherence of porcelain to four representative high-palladium alloys of the
      first generation (Pd-Cu-Ga) and second generation (Pd-Ga) was measured by use of
      a gold-palladium alloy as a control. The area fraction of adherent porcelain
      after metal-ceramic specimens were debonded in biaxial flexure at constant strain
      was calculated from the characteristic Si x-ray intensity with a standardized
      scanning electron microscope/energy-dispersive spectroscopy technique (SEM/EDS).
      The gold-palladium alloy exhibited the highest percentage of cohesive fracture
      through the porcelain, the two first-generation alloys were intermediate, and the
      two second-generation alloys exhibited the lowest area fractions. This study
      demonstrated that conventional visual (naked eye) or microscopic examination of
      the fractured metal-ceramic specimens at moderate magnification and the use of
      standard quantitative metallographic techniques were inadequate to provide
      accurate measurements of the area fraction covered with porcelain.

PMID- 8254539
TI  - A shear stress analysis of the bonding of porcelain veneers to enamel.
AB  - This study demonstrated the relative strengths of the composite resin bond to
      etched enamel and the composite resin bond to surface-treated porcelain with
      similar conditions. It also compared the strength of a combined
      porcelain/composite/enamel bond with the strengths of porcelain/composite resin
      and enamel/composite resin bonds and evaluated the effectiveness of silane
      treatment of the etched porcelain. The influence of thermocycling was also
      investigated. There were 20 samples for each five categories: (1) composite
      resin/etched porcelain; (2) composite resin/etched and silane-treated porcelain;
      (3) composite resin/acid-etched enamel; (4) etched porcelain/composite resin/acid
      etched enamel; and (5) etched and silane-treated porcelain/composite resin/acid
      etched enamel. Half in each category were subjected to thermocycling. Shear
      testing and microscopic examination of the fracture sites resulted in the
      following: (1) Shear testing a combined enamel/composite/porcelain bond resulted
      in significantly different values from testing individual enamel/composite resin
      and porcelain/composite resin bond strengths. (2) Silane treatment of the etched
      porcelain recorded a significantly greater shear strength to the merely etched
      samples. (3) Thermocycling did not significantly dilute the effects of silane
      treatment of the etched porcelain surface.

PMID- 8254540
TI  - Effect of surface design on retention of dowels cemented with a resin.
AB  - This study compared the retentive ability of endodontic dowels cemented with a
      resin when the surfaces of the dowels were varied. Dowels of standardized
      material, shape, length, and diameter were cemented with an unfilled Bis-GMA
      resin. Four dowel surface configurations were tested: transverse serrated,
      crosshatched, threaded, and longitudinal spirals. The results indicated that the
      dowel surface design can significantly influence the retention of a resin
      cemented dowel. Dowels with transverse serrations or crosshatching were retained
      better than dowels with longitudinal spirals or threads.

PMID- 8254541
TI  - A comparison of the bond strengths of microwave- and water bath-cured denture
      material.
AB  - A comparison was made of the shear bond strengths between microwave-polymerized
      and conventional water bath-cured polymethyl methacrylate (PMMA) bonded to
      denture teeth. Four groups of 15 specimens were prepared and shear bond strengths
      obtained by use of standardized laboratory testing methods. The results showed
      that microwave-cured PMMA demonstrated significantly (p 0.0001) higher bond
      strengths than conventional PMMA, and priming of the denture tooth surface with
      monomer liquid yielded significantly higher bond strengths than other surface
      treatment (p 0.0001).

PMID- 8254542
TI  - The shear strength of polymethyl methacrylate bonded to titanium partial denture
      framework material.
AB  - Premachined titanium frameworks are used in implant-supported fixed complete-arch
      prostheses. Traditionally, retentive mechanisms are incorporated in the wax
      patterns to provide retention between polymethyl methacrylate and the cast
      framework. Nontraditional forms of retention are needed with machined frameworks.
      This study determined whether three different surface characteristics of titanium
      improve the bond shear strength of polymethyl methacrylate. Thirty rod shaped
      specimens of titanium were divided into three equal groups: group 1 received no
      pretreatment; group 2 was pretreated with 110 microns alumina air abrasive; and
      group 3 was pretreated with 110 microns alumina air abrasive plus silane (clear).
      Denture resin was processed around each specimen. A Shell-Nielsen shear test was
      then performed at a crosshead speed of 0.5 mm/minute to determine the bond shear
      strength in kilograms per square centimeter. The bond shear strength of group 3
      was 63% greater than group 1 (significant, p < 0.01; ANOVA-Scheffe interval 63
      kg/cm2). The results of this study indicated that surface pretreatment of
      titanium with 110 microns alumina air abrasive plus silane coating significantly
      enhances the bond shear strength of polymethyl methacrylate.

PMID- 8254543
TI  - Quantification of deposits formed in the oral cavity on various materials after a
      1-year period.
AB  - Deposits are formed on natural teeth as well as on various polymeric and metallic
      materials. Deposit formation is complex and controlled by numerous poorly
      understood parameters. This article presents a new method for quantification of
      in vivo deposit formation on multiple materials. Seven different materials were
      positioned at six different sites in the buccal flanges of a removable
      prosthesis. Nine volunteers wore these prostheses for 1 year. The deposits were
      graded by three independent observers under a stereomicroscope at X20
      magnification. Plots of average deposition value averaged for all participants
      and sites are given. Polymethyl methacrylate (PMMA) had the lowest deposition
      value in this trial. The standard error is approximately 15% of the mean value.
      The results show that after 1 year in vivo the roughness of the experimental
      materials increased by a factor of two to six times. The method presented is
      suitable to quantify deposit formation on multiple materials in vivo.

PMID- 8254544
TI  - Assessment of oral implant mobility.
AB  - Most of the implant literature suggests that successful dental implants are
      immobile and any detected mobility indicates implant failure. This study
      evaluated the ability of the Periotest instrument to measure implant mobility in
      a controlled in vitro model with a sample of 56 in vivo implants. In the in vitro
      portion of the study, implant model mobility was determined by an axial testing
      machine (0 to 5 N at 0.2 mm/minute) and the Periotest instrument. The comparison
      showed a high level of correlation (Pearson's r 0.984). The load that the
      Periotest placed on the implants during mobility measurements was approximately 5
      N, depending on the compliance of the test object. The in vivo portion evaluated
      the range of mobility of 56 clinically successful endosseous implants. The range
      of mobility as determined by the Periotest instrument was -6 to +2. This range
      corresponds to an in vitro model displacement (5 N load) of 0.038 mm to 0.113 mm
      with a mean of 0.066 mm +/- 0.018 mm (SD). These data demonstrate that clinically
      successful implants are not immobile, but have a range of mobility.

PMID- 8254545
TI  - Mucosal considerations for osseointegrated implants.
AB  - Tissue resistance is determined by the nature of cells and intercellular contacts
      irrespective of the presence or absence of keratinization, masticatory mucosa, or
      skin. However, these tissues are more easily maintained and less vulnerable to
      inflammation when in contact with dental implants. Lack of masticatory mucosa and
      the presence of alveolar mucosa embracing the implant are often associated with
      plaque, which can induce inflammation resulting in subsequent peri-implant
      destruction. To facilitate proper mechanical oral hygiene maintenance,
      transplantation of autogenous masticatory mucosal grafts at the implant sites was
      performed in patients without attached gingiva, unfavorable vestibulum with
      submucosal muscular activity, and uncontrolled peri-implant mucositis. The
      rationale for having attached mucosa around osseointegrated implants and
      illustration of possible methods of mucosal management in the different phases of
      implant rehabilitation are presented.

PMID- 8254546
TI  - Esthetic and functional considerations for implant restoration of the partially
      edentulous patient.
AB  - Many esthetic and functional considerations are reviewed for the partially
      edentulous implant candidate. With the availability of adjunctive grafting
      procedures, it is time for the implant team to change the traditional treatment
      planning approach that allows patient anatomy to dictate implant position and
      prosthesis design. Dimensions of the edentulous space and evaluation of occlusal
      relationships are discussed. Soft tissue ridge contour and creation of favorable
      cervical harmony are also reviewed. Functional demands unique to the partially
      edentulous patient are outlined in addition to the challenges of creating a
      prosthesis with natural cervical form and emergence profile.

PMID- 8254547
TI  - A fixed-detachable implant-supported prosthesis retained with precision
      attachments.
AB  - The implant-supported, maxillary anterior, fixed-detachable prosthesis is often
      fabricated with a gingival flange to enhance esthetics and phonetics. However,
      only the dentist can remove the prosthesis, and the esthetic labial flange
      invariably impedes patient access for cleaning. A two-piece, fixed-detachable
      prosthesis that incorporates a substructure retained with conventional set screws
      and a superstructure retained with precision attachments has been developed. The
      substructure is contoured to facilitate patient access for oral hygiene because
      it will be covered by the superstructure and neither esthetics nor phonetics is a
      concern. The superstructure is easily removed by the patient for routine cleaning
      and can be designed for favorable esthetics and phonetics. This article reviews
      and describes the procedures for fabrication of this precision attachment
      retained, implant-supported prosthesis.

PMID- 8254548
TI  - Osseointegrated implants in microvascular fibula free flap reconstructed
      mandibles.
AB  - In the past, prosthodontic rehabilitation of patients who underwent segmental
      mandibular resection relied on removable prostheses, which were less than ideal.
      The advent of the microvascular free flap has provided improved appearance and
      function through reconstruction of the skeletal integrity of the mandible. In
      select patients osseointegrated implants strategically placed in the
      reconstructed mandible can be used to restore masticatory function. Patient
      selection criteria and techniques are discussed.

PMID- 8254549
TI  - Technique for controlling the thickness of a facial prosthesis when an acrylic
      resin core is used.
AB  - A technique for evaluating the acrylic resin core before processing a silicone
      facial prosthesis is described. The technique involves the use of either
      irreversible hydrocolloid impression material or silicone to identify thin areas
      in the pattern. This simple yet effective procedure ensures adequate thickness
      and strength of the silicone prosthesis, which in turn decreases the amount of
      chair and laboratory time needed at the delivery appointment.

PMID- 8254550
TI  - Three-dimensional investigation of the accuracy of impression materials after
      disinfection.
AB  - The influence of the two new disinfection systems Hygojet/MD 520 and Impresept on
      the accuracy of eight impression materials was evaluated with a clinically
      relevant abutment arrangement. In addition, an "aseptic" irreversible
      hydrocolloid was tested under the same test conditions but without the
      disinfection procedure. The dimensional changes of all eight impression materials
      related to the disinfection procedures were small. Although statistically
      significant interactions of the impression materials and the disinfection systems
      were found, the influence of the two tested disinfection systems on the
      dimensional accuracy of the impressions does not seem to be clinically relevant.
      From the standpoint of impression accuracy, both tested disinfection systems and
      the tested "aseptic" irreversible hydrocolloid can be recommended for clinical
      and laboratory use.

PMID- 8254551
TI  - Accuracy, detail reproduction, and hardness of gypsum casts produced from
      silicone impressions treated with glow discharge.
AB  - Plasma treatment has been reported to improve the wettability of silicone
      impression materials. This study investigated whether plasma treatment of
      silicone impressions influenced the linear dimensional accuracy, detail
      reproducibility, and surface hardness of models produced from a type IV dental
      die stone. Five silicone impressions materials were used in this study. Linear
      dimensional accuracy and detail reproduction were tested according to ISO
      standards. Surface hardness was evaluated with a Vickers hardness test. The
      results indicated that plasma-treated impressions from Xantopren and Provil
      silicone impression materials had significantly smaller dimensional change than
      their respective controls, and the other materials were not influenced. The
      detail reproduction was superior in casts produced from plasma-treated
      impressions from President silicone. Surface hardness was not influenced by the
      treatment. Plasma treatment of silicone impressions has no negative influence on
      the tested physical properties of die stone models.

PMID- 8254552
TI  - Preliminary report of an experimental design for in vivo testing of bonded
      restorations applied to a new enamel-dentinal bonding agent.
AB  - Because of inconsistency often found between in vitro testing and in vivo
      performance, a new restorative bonding system was evaluated by the placement of
      restorations in vivo in teeth to be extracted. The microleakage was determined
      following extraction after 3 months of clinical service. In each of the sample
      teeth, two restorations were placed on the labial surface, one in the middle of
      the enamel portion and the other extending over the cementoenamel portion. The
      results of this pilot study indicated that bonding to conditioned enamel with the
      new adhesive material is effective, and bonding to conditioned dentin appears to
      be clinically adequate.

PMID- 8254553
TI  - Nutrient intake and gastrointestinal disorders related to masticatory performance
      in the edentulous elderly.
AB  - The effects of chewing efficiency on nutrient intake and the prevalence of
      gastrointestinal disorders were determined in edentulous elderly subjects. Three
      hundred sixty-seven noninstitutionalized individuals aged 60 years and over were
      interviewed. Denture masticatory performance and the collection of dietary
      information were assessed with the "Swallowing Threshold Test Index" and a food
      frequency questionnaire. Approximately half (47%) of the participants exhibited a
      low masticatory performance classification. Thirty-nine percent used the same
      prosthesis for more than 10 years and 28% were taking some medication for
      gastrointestinal disorders. Lower intakes of fruits and vegetables for both sexes
      and of vitamin A by women were observed in subjects with poor masticatory
      performance. Furthermore, subjects with poor masticatory performance took
      significantly more drugs (37%) than those with superior performance (20%). A
      reduced consumption of high-fiber foods could therefore induce the development of
      gastrointestinal disorders in edentulous elderly subjects with a deficient
      masticatory performance.

PMID- 8254554
TI  - Effect of heat-curing cycle and gypsum contamination on the bond strengths of
      composite bonded to a silane-treated alloy.
AB  - Silane-coated alloy specimens bonded to composite resin were tested for shear
      bond strengths and compared with an identical specimen group exposed to gypsum
      invested heat-processing conditions. The results indicate that the bond of
      composite resin to silane-coated alloy is not impaired by investing, boil-out,
      cleaning, packing, and curing during the process of securing artificial teeth to
      a partial denture framework. In a second part of this study, the alloy specimens
      were silane-coated and exposed to the gypsum invested heat-processing procedure
      before the composite resin was bonded to them. In addition, the specimens were
      exposed to one of three different cleaning agents (ethyl acetate, ethyl alcohol,
      and soap and water). Results in the second part of the study indicate that ethyl
      acetate is an effective cleaning agent to use when a silane-coated alloy surface
      previously exposed to gypsum processing is to be bonded to composite resin.

PMID- 8254555
TI  - Preventing bacterial colonization associated with two types of implant abutments.

PMID- 8254556
TI  - A simple method for permanent identification of porcelain veneered crowns and
      fixed partial dentures.

PMID- 8254557
TI  - Locating the swallowed interim prosthesis.

PMID- 8254558
TI  - A procedure for making remount casts without blocking out undercuts.

PMID- 8254559
TI  - Use of a visible light curing resin material for the fabrication of an intranasal
      stent.

PMID- 8254560
TI  - A modified rubber dam clamp.

PMID- 8254561
TI  - Death anxiety and death denial: Nigerian and Australian students' metaphors of
      personal death.
AB  - Ninety-two Nigerian students and 114 Australian students completed Templer's
      (1970) Death Anxiety Scale (DAS) and Feifel and Nagy's (1981) death fantasy
      measure of positive and negative death metaphors. They were each also asked to
      write his or her own metaphor of personal death. Results of the DAS showed that
      the two groups did not differ significantly on the level of conscious death
      anxiety, but Nigerian students' scores were significantly higher on both positive
      and negative personal death metaphors scales. Also, significantly more Nigerian
      students wrote personal metaphors of their own and more often used a neutral
      metaphor to describe their personal death. Australian students more often used a
      positive or a negative metaphor. The Nigerian students thus evidenced less death
      denial than the Australian students did.

PMID- 8254562
TI  - Sex differences in formal operations.
AB  - Research relating cognitive development to gender has been rather limited. The
      few studies that have explored such a relationship have been conclusive. The
      object of this study was to explore whether African students' performance on
      formal operations measure would be related to whether they were male or female.
      The results showed that gender was not related to performance on formal
      operations, as the mean difference between the two sets of subjects was
      statistically nonsignificant.

PMID- 8254563
TI  - Sex role orientation and expectations about counseling.
AB  - We examined the relationship between sex role orientation and expectations about
      counseling in 121 female and 127 male college students who completed the Bem
      (1974) Sex Role Inventory and the Expectations About Counseling Questionnaire
      (Tinsley, Workman, & Kass, 1980). Using multiple regression analyses, we
      identified significant predictors for 15 of the 17 scales, with femininity
      accounting for most of the explained variance. Gender accounted for little
      variance across all variables.

PMID- 8254564
TI  - The belief in a just world and perceptions of discrimination.
AB  - We examined the relationship between the belief in a just world and frequency of
      self-reported acts of personal discrimination. American adults with a strong
      belief in a just world reported fewer acts of personal discrimination against
      themselves than those with a weak belief in a just world. Among the various
      domains of discrimination, the belief in a just world correlated most strongly
      with religious discrimination. People with a strong belief in a just world felt
      that they would be less likely to provide special programs and funding based
      solely on a person's age; they did not feel that age discrimination was prevalent
      in American society.

PMID- 8254565
TI  - Local interneurons and information processing in the olfactory glomeruli of the
      moth Manduca sexta.
AB  - Intracellular recordings were made from the major neurites of local interneurons
      in the moth antennal lobe. Antennal nerve stimulation evoked 3 patterns of
      postsynaptic activity: (i) a short-latency compound excitatory postsynaptic
      potential that, based on electrical stimulation of the antennal nerve and
      stimulation of the antenna with odors, represents a monosynaptic input from
      olfactory afferent axons (71 out of 86 neurons), (ii) a delayed activation of
      firing in response to both electrical- and odor-driven input (11 neurons), and
      (iii) a delayed membrane hyperpolarization in response to antennal nerve input (4
      neurons). Simultaneous intracellular recordings from a local interneuron with
      short-latency responses and a projection (output) neuron revealed unidirectional
      synaptic interactions between these two cell types. In 20% of the 30 pairs
      studied, spontaneous and current-induced spiking activity in a local interneuron
      correlated with hyperpolarization and suppression of firing in a projection
      neuron. No evidence for recurrent or feedback inhibition of projection neurons
      was found. Furthermore, suppression of firing in an inhibitory local interneuron
      led to an increase in firing in the normally quiescent projection neuron,
      suggesting that a disinhibitory pathway may mediate excitation in projection
      neurons. This is the first direct evidence of an inhibitory role for local
      interneurons in olfactory information processing in insects. Through different
      types of multisynaptic interactions with projection neurons, local interneurons
      help to generate and shape the output from olfactory glomeruli in the antennal
      lobe.

PMID- 8254566
TI  - Directional characteristics of tuberous electroreceptors in the weakly electric
      fish, Hypopomus (Gymnotiformes).
AB  - This paper is an electrophysiological study of the directionality of the tuberous
      electroreceptors of weakly electric fish. We recorded from two classes of
      tuberous electroreceptors known for pulse gymnotiforms: Burst Duration Coders
      (BDCs), and Pulse Markers (PMs). Both code for stimulus amplitude, although the
      dynamic range for BDCs is greater, and both exhibit strong directional
      preferences. Polar plots of spike number (for BDCs) or spike threshold (for PMs)
      versus electric field azimuth, are figure-8 shaped with two asymmetrical,
      elliptical lobes separated by 180 degrees. The best azimuth of these two types of
      receptors from a given body region correlate with each other and with measures of
      best azimuth for transepidermal current flow. The shape and asymmetry of the
      directionality profiles appear to be caused by filter dynamics of the receptors.
      Pulse Markers are located on the anterior part of the body surface while Burst
      Duration Coders are located all over. The best directions of receptors in the
      anterior third of the body vary systematically with location from 0 degrees to
      180 degrees. This region is probably critical for determining the direction of
      local electric fields. Together these receptors provide the CNS with sufficient
      information to construct a map of horizontal plane electric field directions.

PMID- 8254567
TI  - Directional sensitivity of tuberous electroreceptors: polarity preferences and
      frequency tuning.
AB  - This paper examines the directionality of tuberous electroreceptor responses and
      relates them to a polarity bias seen for passive electrolocation by electric fish
      (Hypopomus). We recorded from Burst Duration Coders (BDCs) while stimulating with
      1 kHz single period sine waves with electric fields oriented horizontally in
      different directions. Electroreceptors have figure-8 directional sensitivity
      profiles with two, usually unequal lobes of sensitivity separated by 180 degrees.
      For most units the larger lobe points inward, while for a few, the lobes are
      symmetrical or the larger lobe points outward. The differences correlate with
      differences in frequency tuning of the receptors. We can alter, and even reverse,
      the directional asymmetry of a single unit by changing the frequency of the
      stimulus. Two general response profiles results, with two corresponding classes
      of tuning curves. The degree of asymmetries and the effects of stimulus frequency
      and of tuning can be modeled with a linear/non-linear/linear cascade filter. The
      behavioral preference for approaching the head end (+) of an electrode is
      difficult to understand in light of the asymmetry of responses we report for
      amplitude-coding BDCs but can be understood by reference to the time-coding Pulse
      Marker (PM) receptors.

PMID- 8254568
TI  - Isolation of an egg-laying hormone-binding protein from the gonad of Aplysia
      californica and its localization in oocytes.
AB  - A protein solubilized from a membrane preparation of the gonad of Aplysia
      californica has been isolated by affinity chromatography, using bag cell egg
      laying hormone (ELH) as the bound ligand, and partially purified and
      characterized by gel electrophoresis. The protein has an apparent molecular
      weight of 52 kDa and consists of two disulfide-linked subunits of about 30 kDa
      each. The protein is glycosylated and has an acidic pI. Approximately 10-15
      micrograms of this protein can be isolated from a single ovotestis, representing
      less than 1% of the total protein in the gonad; but the protein could not be
      detected in buccal mass or body wall, tissues which do not have apparent response
      to ELH. Antibodies generated against this ELH-binding protein (ELHBP) were used
      to localize sites in the ovotestis which might contain this molecule and thus
      represent targets for egg-laying hormone. Immunocytochemical results indicate
      that the oocytes are a rich source of this protein, since their cytoplasm was the
      only detectable site of immunoreactivity. Whether this binding protein represents
      an egg-laying hormone receptor is uncertain, but its prevalence in oocytes
      suggests that ELH plays a signaling role on these gametes.

PMID- 8254569
TI  - Use of therapeutic milieu in a community setting.
AB  - 1. Many of the same components that contribute to the success of milieu therapy
      in inpatient facilities also promote treatment success for clients living in the
      community. 2. Treatment goals at the Rosati Center, a transitional residential
      program for chronically mentally ill homeless persons in St. Louis, generally
      include supporting residents as they secure their own permanent housing; helping
      residents apply for entitlements so that they can support themselves upon
      discharge; connecting residents with outpatient psychiatric treatment; and
      assisting residents to structure their time and activities as a means to
      improving coping skills. 3. Program evaluations of the transitional living
      program at the Rosati Center revealed that implementation of therapeutic milieu
      concepts (in combination with case management concepts) can be successful. The
      facility served 228 persons during a 5 1/2-year period. Nearly half of those
      persons were discharged having fully met the objectives of the transitional
      program.

PMID- 8254570
TI  - Stress and coping behavior of nurses in Desert Storm.
AB  - 1. Though 100% of the nurses viewed the experience as positive, findings from
      other studies reinforce the importance of combat stress related factors on
      noncombatant personnel in the combat zone. 2. The single most agreed-upon
      stressor was reported as "lack of leadership response," which included lack of
      information, direction, and recognition. There was a positive correlation between
      perceived lack of leadership and the seeking of increased authority behavior in
      command officers. 3. Factors contributing most to maintaining positive working
      conditions were described as "developing psychologic coping skills" or "support
      from friends and socialization." 4. Those nurses who were older and had more
      education used the most effective coping behaviors.

PMID- 8254571
TI  - Medication: reasons and interventions for noncompliance.
AB  - 1. There is a strong correlation between medication noncompliance and higher
      rates of illness relapse. The causes of noncompliance include side effects,
      knowledge deficits, and patient/therapist relationships. 2. The nurse's ongoing
      assessment and understanding of the patients' reasons for treatment resistance is
      the key to promoting medication compliance. 3. Because compliance requires
      patients' complete understanding of their illness and their need for medication
      treatment, patient education is the initial intervention in promoting medication
      adherence. 4. The patient must no longer be viewed as the guilty party. The
      promotion of medication compliance must be the responsibility of both the health
      care professional and the patient.

PMID- 8254572
TI  - How do inpatients with bipolar disorder evaluate diagnostically homogeneous
      groups?
AB  - 1. The results of this study suggest that inpatients with bipolar disorder
      consider diagnostically homogeneous group therapy to be beneficial. All the
      patients who responded to the overall helpfulness criterion indicated that the
      group was helpful to them, and most indicated that it was very helpful. 2.
      Although relating with others may have been important to participants, it is easy
      to appreciate that understanding the disorder would be a top priority for
      inpatients. 3. Inpatients with bipolar disorder might benefit from groups that
      are structured to include topic-oriented didactic and discussion components.

PMID- 8254573
TI  - Sustaining a career.

PMID- 8254574
TI  - How does parallel process manifest itself in psychiatric nursing practice?

PMID- 8254575
TI  - My dream come true.

PMID- 8254576
TI  - Psychiatric nurses must be held accountable for their actions.

PMID- 8254577
TI  - Alzheimer's disease: nursing interventions for clients and caretakers.
AB  - 1. Senile dementia Alzheimer's type (SDAT), a progressive, degenerative disorder,
      affects tissues of the brain, causing a loss of neurons. This process results in
      brain atrophy, specifically in the frontal and temporal regions where integration
      of new information and memory retrieval occur. 2. Increasing age is the single
      most well-established risk factor for the development of SDAT (Brody, 1989).
      Because increasing age is the primary risk factor for the development of SDAT and
      because the elder population is increasing, the number of afflicted persons will
      probably rise (Ham, 1990). 3. The objectives of nursing interventions are to
      assist the client in remaining as independent as possible; to function at the
      highest possible cognitive, physical, emotional, and social levels; and to
      support the family and/or significant others in effectively carrying out their
      functions and goals.

PMID- 8254578
TI  - Structural specificity of polyamines in modulating the binding of estrogen
      receptor to potential Z-DNA forming sequences.
AB  - Estrogen receptor (ER) is a gene-regulatory protein that mediates the action of
      estradiol. In order to examine the role of conformational dynamics of DNA in
      estrogenic regulation of gene expression, we studied the binding of ER to poly(dA
      dC).poly(dG-dT) which undergoes transition to a left-handed Z-DNA form. This type
      of dinucleotide repeats are widely distributed in mammalian genome and are
      present in estrogen response elements. Binding affinity of ER for the
      polynucleotide was assessed by its ability to release ER bound to DNA-cellulose.
      ER binding by poly(dA-dC).poly(dG-dT) was enhanced in the presence of an
      endogenous polyamine, spermidine, H2N(CH2)4NH(CH2)3NH2. The concentration of
      spermidine required for facilitating 50% elution of ER (EC50) was 75 microM. This
      EC50 increased to 500 microM for a spermidine homolog, H2N(CH2)8NH(CH2)3NH2,
      demonstrating polyamine structural specificity. Spectroscopic measurements showed
      that the presence of 100-200 microM spermidine initiated changes in the
      conformation of the polynucleotide indicative of Z-DNA form, but a major
      alteration to Z-DNA spectrum occurred only at 300 microM concentration. These
      data suggest that ER favors DNA sequences poised for Z-DNA transition. The
      efficacy of spermidine homologs in facilitating ER-DNA interaction may be
      important in predicting their efficiency to replace cellular functions of
      spermidine.

PMID- 8254579
TI  - Nonlinear regression analysis of the time course of ligand binding experiments.
AB  - The binding and release of hormones and growth factors are often relatively slow
      processes under biological conditions. Consequently, a knowledge of the
      underlying rate constants may be of greater physiological relevance than the
      equilibrium constant. Here we show how, by following a single time course of
      binding, the rate constants for both binding and release can be determined. The
      ratio of these rate constants allows the binding constant to be calculated. A
      nonlinear regression computer program is described which facilitates these
      calculations and which provides estimates and standard errors of the constants
      determined. The method is illustrated by the binding of human growth hormone to
      the human growth hormone binding protein, and the binding of ovine prolactin to
      the rabbit prolactin receptor.

PMID- 8254580
TI  - Investigation on the potential role of the Ah receptor nuclear translocator
      protein in vitamin D receptor action.
AB  - The Ah receptor nuclear translocator protein (ARNT) is required for binding of
      the Ah (dioxin) receptor to the xenobiotic responsive element (XRE), and is a
      structural component of the XRE-binding form of the Ah receptor. The vitamin D
      receptor requires an accessory protein for binding to the vitamin D responsive
      element (VDRE) in the osteocalcin gene. Since the vitamin D receptor has
      similarities to the Ah receptor, we investigated whether ARNT is also required
      for vitamin D receptor activity. Two lines of evidence demonstrate that ARNT is
      not required for vitamin D receptor activity, and therefore does not correspond
      to the vitamin D receptor accessory protein: i) Antibodies to ARNT have no effect
      on binding of the vitamin D receptor to the VDRE. ii) c4, a mutant of Hepa-1
      cells that is defective in ARNT activity, and in which binding of the Ah receptor
      to the XRE does not occur, possesses a vitamin D receptor with full activity for
      binding the VDRE.

PMID- 8254581
TI  - Decreased insulin-like growth factor-I (IGF-I) receptor sites on circulating
      mononuclear cells from cows with persistent lymphocytosis.
AB  - Plasma IGF-I concentrations and IGF-I receptor binding on mononuclear cells have
      been studied on bovine leukemia virus (BLV)-negative (CO), BLV-infected aleukemic
      (AL) cows or cows with persistent lymphocytosis (PL). No significant differences
      in plasma IGF-I concentrations were demonstrated among the three groups of
      animals. However, a linear negative correlation existed between the number of
      circulating mononuclear cells and the number of IGF-I binding sites on these
      cells from control cows. In addition, mononuclear cells from PL cows had fewer
      IGF-I binding sites per cell when compared with control cows. These results
      suggest involvement of IGF-I in etiology of BLV infection and progression and
      warrant further studies to establish whether IGF-I plays a major physiological
      role in these conditions.

PMID- 8254582
TI  - Modulation of calcitonin binding by calcium: differential effects of divalent
      cations.
AB  - Binding of salmon calcitonin to bovine hypothalamic membranes is enhanced about
      25% by calcium with a half-maximal effect at 15 mM calcium. In contrast,
      membranes prepared from a cell line expressing a recombinant human calcitonin
      receptor show no effect of calcium under similar conditions. The hypothalamic
      calcitonin receptor solubilized with CHAPS detergent retains an apparent Kd of
      0.3 nM for salmon calcitonin; however, binding of calcitonin to the detergent
      solubilized receptor complex can be inhibited by divalent cations in order of
      potency Mn > Ca approximately Sr approximately Mg >> NaCl with Mn and Ca having
      apparent Ki's of 5 mM and 20 mM respectively. Dixon and Scatchard plots of Mn and
      Ca inhibition of binding to the soluble receptor complex suggest a noncompetitive
      mechanism of inhibition. Calcium also inhibits calcitonin binding to a detergent
      solubilized recombinant human calcitonin receptor. Inhibition of calcitonin
      binding is observed using two independent methods for determining soluble
      receptor-hormone complex and inhibition is reversed by EDTA.

PMID- 8254583
TI  - Conservative management of urinary incontinence. A symposium.

PMID- 8254584
TI  - Conservative management of urinary incontinence. A symposium.

PMID- 8254585
TI  - Pelvic floor rehabilitation in the treatment of incontinence.
AB  - This study assessed the effectiveness of a pelvic floor rehabilitation program in
      a clinical practice. A retrospective convenience sample of 48 women was evaluated
      pretreatment and posttreatment with follow-up interviews from six months to three
      years. This group consisted of 81% with stress urinary incontinence, 6% with
      unstable bladder and 10% with mixed incontinence. Fecal incontinence was present
      as well in 35% of the subjects. The patients were taught pelvic floor muscle
      exercises and instruction reinforced with electromyographic biofeedback.
      Neuromuscular electrical stimulation was used when clinically indicated. Two
      women did not continue the program beyond the first visit and were excluded.
      Sixty-two percent of patients with two or more visits demonstrated an
      improvement. Thirteen percent were completely dry, and 49% demonstrated a
      significant improvement. Patients with genuine stress urinary incontinence,
      unstable bladder and mixed incontinence showed a 66%, 33% and 50% improvement
      rate, respectively. Fecal incontinence was improved in 63% of women trained in
      pelvic floor muscle exercises. A significant decrease (P < .001) was found in the
      frequency of self-reported leakage at the six-month to three-year follow-up. The
      strength and duration of a pelvic muscle contraction was significantly greater
      between the first and last visit in all patients, regardless of the subjective
      improvement. A pelvic floor rehabilitation program was an effective alternative
      to surgical intervention in reducing the frequency of urinary leakage. Further
      studies are needed to identify factors predicting success and to determine the
      most cost-effective method of achieving pelvic floor rehabilitation.

PMID- 8254586
TI  - Intravaginal maximal electrical stimulation in the treatment of urinary
      incontinence.
AB  - Urinary incontinence imposes a large economic burden, estimated at $10 billion
      per year. As the cost of health care continues to rise, conservative therapeutic
      measures are becoming more attractive. Anecdotal reports suggest that electrical
      stimulation may be up to 87% effective in the treatment of urinary incontinence.
      Investigators use different stimulation devices and protocols and make a
      comparison of results difficult. The true efficacy of electrical stimulation for
      the treatment of urinary incontinence is unknown since there have been no
      controlled clinical trials. Within our referral-based urogynecology practice, we
      employ intermittent, intravaginal maximal electrical stimulation in conjunction
      with bladder drills and pelvic floor exercises. Over a one-year period we treated
      76 women with urinary incontinence: 19 with stress incontinence (SUI), 30 with
      detrusor instability (DI) and 27 with mixed incontinence (MI). After six weeks,
      our overall objective improvement rate was 76%; 89% of patients with SUI, 73%
      with DI and 70% with MI met the criteria for improvement. Long-term follow-up
      averaged 6 months, with a range of 2-12. Of patients who showed an initial
      objective improvement, 87% maintained that improvement. Intravaginal electrical
      stimulation may be effective therapy for urinary incontinence. Controlled
      clinical trials are needed to determine its efficacy and standardize stimulation
      protocols before its widespread use.

PMID- 8254587
TI  - Kegel or cut? Variations on his theme.
AB  - Pelvic floor muscle training has long been recognized as a beneficial treatment
      for urinary incontinence. This paper discusses the concepts of muscle grading
      facilitation and training. Individually designed programs, suitable for the
      patient's current status, are critical to success. It may be tempting to operate,
      but it takes a dedicated health care provider to manage incontinence
      nonsurgically.

PMID- 8254588
TI  - Effect of urinary incontinence on sexual activity in women.
AB  - The effects of urinary incontinence on sexual activity were assessed with a
      questionnaire. Forty-four women were asked about the symptoms of urgency and
      frequency as well as incontinence. Fifty-six percent of the women experienced
      urinary incontinence during sexual activity. Sixty-six percent experienced
      incontinence, urgency or frequency during sexual activity. The women were asked
      to give recommendations to alleviate or adapt to urinary symptoms. A treatment
      model for intervention was developed based on the Permission, Limited
      Information, Specific Suggestion, Intensive Therapy model.

PMID- 8254589
TI  - Graded pelvic muscle exercise. Effect on stress urinary incontinence.
AB  - The purpose of this research was to determine the effect of pelvic muscle
      exercise (PME) on stress urinary incontinence in middle-aged and elderly women.
      The protocol required 16 weeks of exercise three times per week, for a total of
      48 sessions. Measures were taken at baseline, after a 4-week control period and
      after 4, 8, 12 and 16 weeks of PME, corresponding to PME levels 1, 2, 3 and 4,
      respectively. Urine loss was evaluated using a urinary diary and 24-hour pad test
      at baseline, after the control period and after PME levels 2 and 4. Pelvic muscle
      function was evaluated every four weeks. Sixty-five parous women 35-75 years of
      age (mean, 51.3) with mild to moderate stress urinary incontinence were studied.
      No significant changes in the outcome variables were found after the control
      period. The results showed significant reductions in urine loss on the 24-hour
      pad test (t = -4.7, P < or = .0001), and episodes of urine loss decreased from
      2.6 to 1.0 between the control period and PME level 4. In addition, a significant
      improvement occurred in pressures developed by the pelvic muscles in response to
      PME (t = 6.8, P < or = .0001). Significant correlations between changes in pelvic
      muscle pressure and in urine loss variables were not found. Women who completed
      the study experienced a significant reduction in the amount of urine loss as well
      as a significant increase in pelvic muscle characteristics.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8254590
TI  - Absolute male factor infertility. A useful model for evaluating the efficacy of
      cryopreserved semen.
AB  - Cryopreserved semen generally results in diminished pregnancy rates when used for
      donor insemination. However, coexisting female subfecundity may significantly
      confound the pregnancy outcome. Therefore, in order to determine the efficacy of
      cryopreserved semen, 43 consecutive women with absolute male factor infertility
      (single women or wives of azoospermic men) were inseminated with cryopreserved
      spermatozoa using cervical caps. Life table analysis of the results revealed a
      cumulative probability of conception of 84% with a monthly fecundability rate of
      19% after eight insemination cycles. These results are similar to those reported
      using fresh semen, suggesting that the efficacy of cryopreserved semen may be
      higher than previously believed.

PMID- 8254591
TI  - Transverse versus longitudinal uterine incision in cesarean delivery of triplets.
AB  - It is commonly accepted that cesarean section is the preferred mode of delivery
      of triplets. The present study was performed to evaluate maternal complications
      and neonatal outcome in 21 women operated on by a transverse lower segment
      incision as compared to 8 parturients who underwent surgery by a longitudinal
      uterine incision. There was no significant difference in mean gestational age at
      delivery, mean weight of the newborns, Apgar scores, perinatal mortality rates,
      or intraoperative or postpartum hemorrhage incidence between the two groups.
      Thus, a transverse lower segment uterine incision should be used in triplet
      deliveries to increase the chances of a normal vaginal delivery in the future.

PMID- 8254592
TI  - Gamete intrafallopian transfer. An overview.
AB  - Gamete intrafallopian transfer involves a direct transfer of both human gametes,
      sperm and oocytes, into the fallopian tube. Since the first report of a
      successful pregnancy following the use of this technique by Asch et al in 1984,
      its role in the treatment of infertile women with patent tubes has been
      established. Recent data demonstrate a 34.4% clinical pregnancy rate, with the
      highest pregnancy rate achieved in infertile women due to endometriosis or
      unexplained infertility.

PMID- 8254593
TI  - Effect of insulin-dependent diabetes on plasma lipoproteins in diabetic
      pregnancy.
AB  - A reduction in total plasma cholesterol concentration has been reported in
      insulin-dependent diabetic (IDDM) pregnant women in early gestation. To determine
      if this reduction extends throughout gestation and which lipoprotein fractions
      may be responsible, we measured plasma triglyceride, cholesterol (C), high
      density lipoprotein cholesterol (HDL-C) and HDL2 and HDL3-C subfractions between
      6 and 36 weeks' gestation in normal and IDDM women. Total plasma C was
      significantly lower in IDDM pregnant subjects between 20 and 36 weeks' gestation
      as compared to nondiabetic controls, while plasma triglyceride concentrations
      were not significantly different in this interval. Very low and low density
      lipoprotein (VLDL, LDL) C concentrations were not statistically significantly
      different from controls at any of the times studied, while HDL-C was lower
      throughout diabetic pregnancy as compared to controls, significantly so between
      20 and 36 weeks' gestation. The lower HDL-C in IDDM women was associated with a
      significantly lower HDL3-C level. Plasma apoprotein A-I and A-II concentrations,
      markers of the HDL2 and HDL3 subclasses, respectively, were measured to
      corroborate the HDL subfraction changes. Apo A-I and A-II increased significantly
      between 12 and 28 weeks' gestation in control but not in diabetic pregnant
      subjects, consistent with a higher HDL3 in normal than in diabetic pregnant
      subjects. It appears that plasma triglyceride, VLDL and LDL-C, and HDL2-C
      concentrations are similar in IDDM and normal pregnancy, while total-C, HDL-C and
      HDL3-C and its associated apoproteins are lower than in normal subjects in late
      gestation. The mechanism of these changes and their significance for fetal growth
      and development deserve further study.

PMID- 8254594
TI  - Intrauterine insemination. Effect of wash media on pregnancy rates and sperm
      motility.
AB  - Testyolk Buffer has been shown to enhance sperm penetration in hamster
      penetration assays and increase fertilization of oocytes in in vitro
      fertilization. Based on these findings, we compared pregnancy rates and sperm
      motility in intrauterine inseminations done with sperm samples washed and
      resuspended in Ham's F10 as compared with Testyolk buffer. Charts were reviewed
      retrospectively from 1,098 husband and donor intrauterine inseminations performed
      at the University of Florida. Data were analyzed using life table analysis and
      the curves compared with the Mantel-Haenszel statistical test. In addition, sperm
      motility in fresh sperm was observed in samples incubated in Testyolk or Ham's
      F10, with motility counts performed at 0, 6 and 24 hours. Four hundred ninety-two
      Testyolk cycles and 579 Ham's F10 cycles were compared, with cumulative pregnancy
      rates at one year of 53% and 44%, respectively (P = .58). With donor sperm, 229
      cycles with Testyolk and 314 cycles with Ham's F10 had cumulative pregnancy rates
      of 68% and 48%, respectively (P = .52). With husband insemination, 264 Testyolk
      and 253 Ham's F10 cycles had pregnancy rates of 37% and 35%, respectively (P =
      .23). Fresh sperm motility in 22 samples compared at 0, 6 and 24 hours in Ham's
      F10 (76%, 67.8%, 56.6%) versus Testyolk (76%, 67.7%, 58.8%) revealed no
      significant differences. There was also no difference in total motile sperm
      inseminated and postwash motility in 1,098 samples with Testyolk versus Ham's
      F10. This study demonstrates that there is no enhanced pregnancy rate or
      increased sperm motility when sperm are treated with Testyolk Buffer instead of
      Ham's F10.

PMID- 8254595
TI  - Vaginal birth after cesarean section. Acceptance and outcome at a rural hospital.
AB  - A retrospective review of all pregnant women with a history of cesarean section
      was conducted at an isolated military hospital. During the two-year period 1988
      1989, 62 patients were initially considered eligible for attempting vaginal birth
      after cesarean section (VBAC). Seventy-nine percent (49/62) of the patients
      initially requested a trial of labor, and 14 of them ultimately did not meet
      American College of Obstetricians and Gynecologists criteria. Three patients
      reversed their decision late in pregnancy. Eighty-eight percent (28/32) of those
      undergoing a trial of labor delivered vaginally. The three patients with more
      than one prior cesarean section all delivered vaginally. The four failures
      occurred in patients who had a history of well-documented cephalopelvic
      disproportion. Perinatal morbidity consisted of intrauterine fetal demise prior
      to the onset of labor at 40 weeks' gestation. Maternal morbidity included
      postcesarean endometritis (n = 1) and vaginal sidewall laceration (n = 1). These
      results indicate that in a rural hospital VBAC was well accepted by patients and
      was safe; however, further study is required.

PMID- 8254596
TI  - Female genital tract abscess formation in the rat. Use of pathogens including
      enterococci.
AB  - Previous animal experiments utilizing bowel flora have demonstrated synergy
      between various aerobes and anaerobes in the formation of intraabdominal
      abscesses. In these experiments, human female genital tract isolates were
      inserted into the abdominal and pelvic cavities of 151 female Sprague-Dawley
      rats. Inoculation with any single species of organism--Streptococcus faecalis,
      Enterobacter cloacae or Bacteroides bivius or a combination of two facultative
      organisms (S faecalis plus E cloacae)--did not result in a significant increase
      in abscess formation. Combination of a facultative organism or organisms with the
      anaerobe B bivius or S faecalis plus B bivius plus E cloacae resulted in 55% (P <
      .01) and 74% (P < .0005) rates of abscess formation, respectively, as compared
      with controls. Combinations including B fragilis demonstrated similar results.
      Thus, female genital tract facultative organisms demonstrate synergy in the
      presence of anaerobic organisms in the development of abscesses.

PMID- 8254597
TI  - Microcolposcopy. When and how to do it.
AB  - Microcolposcopy is a valuable accessory technique for the busy colposcopist and
      is particularly helpful in locating the new squamocolumnar junction.
      Microcolposcopy is an evaluation of cytology, and colposcopy is a study of
      vascular and growth patterns. The two methods are complementary.

PMID- 8254598
TI  - Evaluation of prognostic factors for vaginal delivery after cesarean section.
AB  - Although the success rate of vaginal birth after cesarean section in selected
      patients is > 60%, most of these women elect the option of a planned repeat
      cesarean section. In this study our purpose was to evaluate the predictive value
      and relative importance of 15 prognostic factors by using univariate and
      multivariate analysis in order to refine the selection of patients for a trial of
      labor. The analyses were based on 261 patients with one prior cesarean section
      who were allowed a trial of labor. The final model resulted in six significant
      prognostic factors. The overall predictive value of the model was 68%. However,
      the predictive value for a successful vaginal delivery was excellent: 94.5%
      (139/147) of the women predicted to deliver vaginally actually did so. This group
      constituted 56% (147/261) of our candidates for vaginal delivery. The predictive
      value of the test for failure was only 33.3% (38/114); 66.6% of the women
      completed a vaginal delivery despite the prediction of failure. Because the
      chance of a successful vaginal delivery is > 60% in women with a prediction of
      failure, until a selection criterion with a better prognostic value can be
      identified, a liberal approach to vaginal birth after cesarean section is
      justified even in this group. A 60% chance is perceived by many women and
      physicians as too low to elect this option. Since we were able to predict a
      successful vaginal delivery in a large proportion of the candidates, it may
      encourage at least this group of patients to elect a trial of labor.

PMID- 8254599
TI  - Delayed birth intervals of immature fraternal triplets in preterm labor. A case
      report.
AB  - The preterm birth of immature triplets before 28 weeks is associated with excess
      morbidity and mortality risks attributable to extreme immaturity. We report a
      case of fraternal triplets in preterm labor in which the second and third triplet
      births were delayed 11 days after the first birth, at 26 4/7 weeks' gestation.
      The later-born sibs were heavier at birth and throughout their neonatal course in
      the hospital and suffered less severe complications as compared to the first-born
      triplet. Delayed birth intervals of triplets in preterm labor should be
      considered to improve perinatal salvage of immature triplets, although a
      successful outcome is rare and unexpected.

PMID- 8254600
TI  - Chronic disseminated intravascular coagulation caused by a uterine leiomyoma. A
      case report.
AB  - We report the case of a patient who presented with a large abdominopelvic mass
      and laboratory data consistent with disseminated intravascular coagulation. After
      the successful removal of a large uterine leiomyoma, the patient's coagulopathy
      resolved.

PMID- 8254601
TI  - Leiomyomas of the fallopian tube. A case report.
AB  - Both heterotopic pregnancies and primary neoplasms of the fallopian tube are rare
      occurrences. A patient presented with early pregnancy, abdominal pain and
      ultrasound findings of an intrauterine gestation and a fallopian tube mass.
      Laparotomy revealed a primary leiomyoma of the fallopian tube.

PMID- 8254602
TI  - Urethral stones in women. A case report.
AB  - Urethral stones are encountered rarely in the urethra in women. We report the
      clinical and urodynamic findings and the management of 17 stones in a urethral
      diverticulum.

PMID- 8254603
TI  - Normal fetal outcome in a pregnancy with central nervous system toxoplasmosis and
      human immunodeficiency virus infection. A case report.
AB  - A pregnant woman was diagnosed with central nervous system toxoplasmosis and
      human immunodeficiency virus infection. Diagnosis was made by evaluating computed
      tomography scan results and toxoplasma antibody titers. The patient was treated
      with pyrimethamine and sulfadiazine, with an excellent fetal outcome. She
      responded well to this regimen but developed a delayed exanthematous
      hypersensitivity reaction. Treatment with a substitute regimen resulted in a
      recurrence of symptoms, leaving undesirable neurologic deficits.

PMID- 8254604
TI  - Phe3-substituted analogues of deltorphin C. Spatial conformation and topography
      of the aromatic ring in peptide recognition by delta opioid receptors.
AB  - In order to study the contribution of the electronic, hydrophobic, and
      conformational properties of the amino acid residue at position 3 in deltorphin C
      on binding to delta and mu opioid receptors, a series of 5- and 6-membered ring
      and bicyclic amino acid replacements at position 3 were prepared by solution
      synthesis methods. In general, the substitutions were deleterious for high delta
      affinity (Ki delta) and delta selectivity (Ki mu/Ki delta). However, several
      notable exceptions were recognized: peptides containing the constrained, bicyclic
      structures Aic3 and (R or S) Atc3 enhanced delta affinity, but only the latter
      increased delta selectivity 4-fold (= 2475) relative to deltorphin C (= 661); at
      the other extreme, delta affinity of N alpha MePh3 fell 900-fold. Bioassays of [N
      alpha MePhe3]-, [(R or S)C alpha MePhe3]-, [Tic3]-, [Aic3]-, and [(R or S)
      Atc3]deltorphin C using guinea pig ileum (GPI) and mouse vas deferens (MVD) for
      mu and delta bioactivity, respectively, revealed a significant correlation (r =
      0.916) between MVD bioactivity and delta binding in brain membranes. [(R or
      S)Atc3]deltorphin C also exhibited the highest biological selectivity (GPI/MVD)
      (= 3,522), which was 3-fold greater than that observed for deltorphin C.
      Molecular modelling of [N alpha MePhe3]- and [(S)Atc3]deltorphin C established
      that these amino acid replacements for Phe3 produce alterations in the backbone
      (phi,psi) and side-chain (chi 1,chi 2) dihedrals which critically affect the
      flexibility of the peptide and possibly limit accessible conformations for its
      alignment within the delta opioid receptor. The data provide evidence that the
      delta receptor is sensitive to changes in the composition, conformation, and
      orientation of the side chain of residue 3 of a linear opioid heptapeptide.

PMID- 8254605
TI  - Solvent-dependent conformation and hydrogen-bonding capacity of cyclosporin A:
      evidence from partition coefficients and molecular dynamics simulations.
AB  - The partition coefficient of cyclosporin A (CsA) was measured in octanol/water
      and heptane/water by centrifugal partition chromatography. By comparison with
      results from model compounds, it was deduced that the hydrogen-bonding capacity
      of CsA changed dramatically from an apolar solvent (where it is internally H
      bonded) to polar solvents (where it exposes its H-bonding groups to the solvent).
      Molecular dynamics simulations in water and CCl4 support the suggestion that CsA
      undergoes a solvent-dependent conformational changes and that the interconversion
      process is slow on the molecular dynamics time scale.

PMID- 8254606
TI  - Cyclic GMP phosphodiesterase inhibitors. 1. The discovery of a novel potent
      inhibitor, 4-((3,4-(methylenedioxy)benzyl)amino)-6,7,8-trimethoxyquinazoline.
AB  - A newly synthesized compound, 4-((3,4-(methylenedioxy)benzyl)amino)-6,7,8
      trimethoxyquinazoline (6), had a potent (IC50 = 0.36 microM) inhibitory action on
      cyclic GMP phosphodiesterase (cGMP-PDE) isolated from porcine aorta; its
      inhibitory activities toward other PDE isozymes were at least 10-fold weaker. In
      addition, 6 relaxed porcine coronary arteries precontracted with PGF2 alpha (EC50
      = 1.96 +/- 0.58 microM). At the concentration of 30 microM, 6 caused elevation of
      the intracellular cGMP level in porcine coronary arteries without any change in
      cAMP level. Various other 4-substituted 6,7,8-trimethoxyquinazolines were also
      synthesized and evaluated for cGMP-PDE inhibitory activity. From their structure
      activity relationships, we concluded that the 4-((3,4-(methylenedioxy)benzyl)
      amino) group is essential for potent inhibition of cGMP-PDE.

PMID- 8254607
TI  - Structure-based design of inhibitors of purine nucleoside phosphorylase. 3. 9
      Arylmethyl derivatives of 9-deazaguanine substituted on the methylene group.
AB  - X-ray crystallography and computer-assisted molecular modeling (CAMM) studies
      aided in the design of a potent series of mammalian purine nucleoside
      phosphorylase (PNP) inhibitors. Enhanced potency was achieved by designing
      substituted 9-(arylmethyl)-9-deazaguanine analogs that interact favorably with
      all three of the binding subsites of the PNP active site, namely the purine
      binding site, the hydrophobic pocket, and the phosphate binding site. The most
      potent PNP inhibitor prepared during our investigation, (S)-9-[1-(3-chlorophenyl)
      2-carboxyethyl]-9-deazaguanine (18b), was shown to have an IC50 of 6 nM, whereas
      the corresponding (R)-isomer was 30-fold less potent.

PMID- 8254608
TI  - Analysis of two cycloplatinated compounds derived from N-(4-methoxyphenyl)-alpha
      benzoylbenzylidenamine. Comparison of the activity of these compounds with other
      isostructural cyclopalladated compounds.
AB  - In the present paper we report the synthesis, structural characterization,
      biochemical properties, and antiproliferative activity of two organo-cis-platinum
      cyclometalated compounds of formula [M(4-OMeC6H4N=C(COC6H5)C6H4)X]2, where M = Pt
      and X=Cl (4) or OAc (5). The IR and 1H and 13C NMR data of the chloro-bridged
      compound 4 showed that it has a planar structure. As indicated by IR and 1H and
      13C NMR, the acetate-bridged compound 5 has an open-book shape structure. This
      structure was further confirmed by X-ray diffraction. The comparison of the
      biochemical properties and antiproliferative activity of these compounds relative
      to the isostructural palladium compounds [Pd(4-OMeC6H4N=C(COC6H5)C6H4)X]2 [X =
      AcO (1) and (2) or Cl (3)] indicated that the activity of compounds 4 and 5 is
      higher than that of the corresponding isostructural compounds 3 and 1-2,
      respectively, since their ID50 are 2-9-fold lower. It seems that there are not
      differences in the antiproliferative activity of all these compounds against
      leukemia HL-60 cells or mammary cancer MDA-MB 468 cells. Compounds 4 and 5 modify
      also the DNA structure of the oc and ccc forms of plasmid DNA. The acetate
      bridged compound 5 showed the highest antiproliferative activity which is even
      higher than that of cis-DPP. Our data indicate that the Pt(II) compounds are more
      active than those having Pd(II) as the metal center.

PMID- 8254609
TI  - Neuropeptide Y: Y1 and Y2 affinities of the complete series of analogues with
      single D-residue substitutions.
AB  - In an effort to gain insight into the bioactive conformation of neuropeptide Y
      upon interaction with its receptors, all single-point D-amino acid substituted
      NPY analogues were prepared, and their Y1 and Y2 receptor binding affinities were
      evaluated using the human neuroblastoma cell lines, SK-N-MC and SK-N-BE2,
      respectively. Solid-phase synthesis (Boc strategy) followed by preparative HPLC
      purification produced analogues of high purity that were characterized by RP
      HPLC, AAA, LSIMS, CZE, and optical rotation. Of the 37 isomers (a naturally
      occurring glycine at position 9 was replaced by Ala and D-Ala), Y1 receptor
      binding was most perturbed by chiral inversion of residues at the C-terminus
      (residues 20, 27, 29-35, Ki > or = 300 nM). Substitutions at residues 2-5, 28,
      and 36 had Ki values ranging from 40 to 260 nM. Substitutions at all other
      positions yielded analogues with affinities ranging from 1.5 to 20 nM. Binding
      affinities to the Y2 class of receptors all measured in the low or sub-nanomolar
      concentrations, with the exception of C-terminally modified isomers (residues 30
      35). Only [D-Arg33]- and [D-Gln34]NPY displayed no measurable binding affinity to
      Y2 receptors at the highest concentration tested (1000 nM). Representative
      analogues were selected on the basis of their binding affinities and position in
      the sequence for structural analysis using circular dichroism (CD) spectroscopy.
      Of the nine peptide evaluated ([D-Pro5]-, [Ala9]-, [D-Glu10]-, [D-Asp11]-, [D
      Ala18]-, [D-Tyr20]-, [D-Tyr27]-, and [D-Arg33]NPY), only [D-Tyr27]NPY expressed a
      definitive correlation between loss of binding affinity and disruption of
      secondary structure by having the propensity to form beta-sheets at the expense
      of alpha-helical content. It was concluded that although the incorporation of a
      single D-amino acid within the sequence of NPY may confer a conformational
      perturbation, the receptor interaction was only affected when certain critical
      residues were modified, findings that provide a basis for the identification of
      the binding pharmacophore of NPY.

PMID- 8254610
TI  - Analyses of ligand binding in five endothiapepsin crystal complexes and their use
      in the design and evaluation of novel renin inhibitors.
AB  - Five renin inhibitors were cocrystallized with endothiapepsin, a fungal enzyme
      homologous to renin. Crystal structures of inhibitor-bound complexes have
      provided invaluable insight regarding the three-dimensional structure of the
      aspartic proteinase family of enzymes, as well as the steric and polar
      interactions that occur between the proteins and the bound ligands. Beyond this,
      subtleties of binding have been revealed, including multiple subsite binding
      modes and subsite interdependencies. This information has been applied in the
      design of novel potent renin inhibitors and in the understanding of structure
      activity relationships and enzyme selectivities.

PMID- 8254611
TI  - Design and synthesis of an orally active macrocyclic neutral endopeptidase 24.11
      inhibitor.
AB  - A potent macrocyclic inhibitor of neutral endopeptidase (NEP) 24.11 was designed
      using a computer model of the active site of thermolysin. This 10-membered ring
      lactam represents a general mimic for any hydrophobic dipeptide in which the two
      amino acid side chains bind to an enzyme in a contiguous orientation. The parent
      10-membered ring lactam was synthesized and exhibited excellent potency as an NEP
      24.11 inhibitor (IC50 = 3 nM). In order to improve oral bioavailability, various
      functionality was attached to the macrocycle. These modifications lead to CGS
      25155, an orally active NEP 24.11 inhibitor that slows down the degradation of
      the cardiac hormone atrial natriuretic factor, producing a lowering of blood
      pressure in the DOCA-salt rat model of hypertension.

PMID- 8254612
TI  - Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral
      endopeptidase 24.11 inhibitors.
AB  - A series of 13- and 14-membered ring lactam derivatives 9a,b, 10, 11, and 12a-c
      was prepared from L-cysteine. Compounds 9a,b and 12a,b were tested in vitro for
      inhibition of neutral endopeptidase 24.11 (NEP) and angiotensin converting enzyme
      (ACE) inhibition. The structure-activity profile of the series is discussed.
      Compound 9b, a 13-membered ring macrocyclic lactam, had an NEP IC50 of 18 nM and
      an ACEIC50 of 12 nM in vitro and showed dual plasma inhibition after intravenous
      or oral administration.

PMID- 8254613
TI  - Synthesis, antiproliferative, and antiviral activity of 4-amino-1-(beta-D
      ribofuranosyl)pyrrolo[2,3-d]pyridazin-7(6H)-one and related derivatives.
AB  - The synthesis of 4-amino-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin-7 (6H)-one
      (3) from the reaction of ethyl 3-cyano-1-beta-D-ribofuranosylpyrrole-2
      carboxylate (10) and hydrazine is described. The 5:6 pyrrolo[2,3-d]pyridazin
      7(6H)-one structure of 3 was established via a three-step conversion of 3 into 1
      beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin-4,7(5H,6H)- dio ne (14). 4-Amino-3
      chloro-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin+ ++-7(6H)-one (16) 4-amino-3
      bromo-1-beta-D-ribofuranosylpyrrolo[2,3-d]pyridazin++ +-7(6H)-one (18) were
      prepared via N-chlorosuccinimide or N-bromosuccinimide treatment of 4-amino-1
      (2,3,5-tri-O-benzyl-beta- D-ribofuranosyl)pyrrolo[2,3-d]pyridazin-7(6H)-one (7)
      followed by a removal of the benzyl groups with boron trichloride. Direct
      treatment of 3 with N-iodosuccinimide furnished 4-amino-3-iodo-1-beta-D
      ribofuranosylpyrrolo[2,3-d]pyridazin -7(6H)-one (19). The antiproliferative
      activity of the compounds was determined in L1210, H. Ep. 2 and several
      additional human tumor cell lines. In L1210 cells, the 3-halo-substituted
      compounds 16, 18, and 19 exhibited significant cytotoxicity (IC50 = 0.2, 0.1,
      0.08 microM, respectively), in contrast to the 3-unsubstituted compound 3, which
      had only slight activity. The greater antiproliferative activity of 18 and 19 in
      contrast to 3 was confirmed in H. Ep. 2 cells and KB cells. The antiviral
      evaluation of these compounds revealed that compounds 16, 18, and 19 were active
      against human cytomegalovirus in both plaque- and yield-reduction assays.
      However, this activity was only partially separated from cytotoxicity in human
      cell lines.

PMID- 8254614
TI  - Synthesis of 2,4-disubstituted thiazoles and selenazoles as potential antitumor
      and antifilarial agents: 1. Methyl 4-(isothiocyanatomethyl)thiazole-2-carbamates,
      -selenazole-2- carbamates, and related derivatives.
AB  - Methyl 4-(isothiocyanatomethyl)thiazole-2-carbamate and methyl 4
      (isothiocyanatomethyl)selenazole-2-carbamate have been prepared via chemical
      transformations involving 2-amino-4-(chloromethyl)thiazole (1) and 2-amino-4
      (chloromethyl)selenazole (2), respectively, as starting materials. The
      homoanalog, methyl 4-(2-isothiocyanatoethyl)thiazole-2-carbamate, was prepared
      from (2-aminothiazol-4-yl)acetic acid. All compounds prepared were evaluated for
      their ability to inhibit leukemia L1210 cell proliferation. Methyl 4
      (isothiocyanatomethyl)thiazole-2-carbamate (7) was the most active compound in
      this screen, inhibiting the growth of L1210 leukemic cells with an IC50 = 3.2
      microM. Mitotic blocking appears to be its primary mechanism of cytotoxic
      activity. Compound 7 also was the only compound which demonstrated significant in
      vivo antifilarial activity against the adult worms of Acanthocheilonema viteae in
      experimentally infected jirds. This compound was inactive against Brugia pahangi
      at a dosage of 100 mg/kg x 5 days.

PMID- 8254615
TI  - Synthesis of 2,4-disubstituted thiazoles and selenazoles as potential
      antifilarial and antitumor agents. 2. 2-Arylamido and 2-alkylamido derivatives of
      2-amino-4-(isothiocyanatomethyl)thiazole and 2-amino-4
      (isothiocyanatomethyl)selenazole.
AB  - The synthesis of a series of 2-arylamido and 2-alkylamido derivatives of 2-amino
      4-(isothiocyanatomethyl)thiazole and 2-amino-4-(isothiocyanatomethyl)selenazole
      is described. In vitro antiproliferative evaluations were carried out using L1210
      cells. The 2-(alkylamido)thiazole derivatives were moderately antiproliferative,
      with IC50's of 4-8 microM. A significant increase in activity was obtained for
      the arylamido derivatives, with IC50's of 0.2-1 microM. The results obtained for
      the selenazoles were similar to those for the thiazoles. 2-Benzamido-4
      (isothiocyanatomethyl)-thiazole (19) was found to be a potent inhibitor of GMP
      synthetase. None of the compounds prepared in this study demonstrated
      antifilarial activity.

PMID- 8254616
TI  - Novel inhibitors of prolyl 4-hydroxylase. 5. The intriguing structure-activity
      relationships seen with 2,2'-bipyridine and its 5,5'-dicarboxylic acid
      derivatives.
AB  - Members of a series of 2,2'-bipyridines have been synthesized and tested as
      inhibitors of prolyl hydroxylase (EC 1.14.11.2). The structure-activity
      relationships seen with [2,2'-bipyridine]-5-carboxylic acid (4) closely resemble
      those of pyridine-2-carboxylic acid (2). Accordingly, [2,2'-bipyridine]-5,5'
      dicarboxylic acid (11, IC50 = 0.19 microM) is the most potent inhibitor of its
      type yet reported. However, 2,2'-bipyridines lacking a 5-carboxylate are poor
      inhibitors. These contrasting structure-activity relationships are discussed in
      terms of net anionic charge, iron chelation, and the availability of alternative
      putative binding modes at a single binding site in each catalytic subunit.

PMID- 8254617
TI  - R2 C-terminal peptide inhibition of mammalian and yeast ribonucleotide reductase.
AB  - Eucaryotic ribonucleotide reductases (RR) catalyze the reduction of
      ribonucleoside diphosphates to 2'-deoxyribonucleoside diphosphates. Each has an
      R1(2)R2(2) quaternary structure with each subunit playing a critical role in
      catalysis. Separation of the subunits results in loss of activity. Previous
      studies have demonstrated that peptides corresponding to the C-terminus of R2
      disrupt subunit association by competion with R2 and have potential usefulness as
      therapeutics. Extensive structure-function studies have been carried out on
      peptide inhibition of herpes simplex RR in an effort to develop antiviral agents
      based on the observation that the herpes simplex R2 C-terminus, YAGAVVNDL, is
      quite different from the corresponding mammalian sequence. In this work we report
      a detailed structure-function analysis of peptide inhibition of mammalian and, to
      a more limited extent, Saccharomyces cerevisiae RRs. Our results for mammalian RR
      support the following conclusions with regard to the effect of substitution on
      inhibitory potency: (a) the N-acetylated R2 C-terminal heptapeptide N
      AcPhe384Thr385Leu386Asp387Ala388Asp389Phe390 (N-AcF7TLDADF1) is the minimal core
      peptide length required; deletion of the N-terminus or of middle positions
      (resulting in penta- and hexapeptides) results in large losses in inhibitory
      potency; (b) a free carboxylate is required on the C-terminal Phe; (c) Phe is
      strongly preferred to Leu in positions 1 and 7 and a bulky aliphatic group is
      preferred in position 5; (d) neither negative charge in positions 2 or 4 nor a
      polar side chain in position 6 are required for peptide binding, contrary to what
      evolutionary patterns in the R2 C-terminus of RR would suggest. S. cerevisiae RR
      displays a similar length dependence on the corresponding N-acetylated R2 C
      terminal heptapeptide, N-AcFTFNEDF. This peptide has a 4-fold higher inhibitory
      potency toward S. cerevisiae RR than toward mammalian RR. Such selectivity raises
      the possibility that peptide analogs related to R2 C-termini can be developed as
      therapeutic agents even against organisms having R2 C-terminal sequences similar
      to that of mammalian RR.

PMID- 8254618
TI  - The NEWLEAD program: a new method for the design of candidate structures from
      pharmacophoric hypotheses.
AB  - We have developed a computer program, called NEWLEAD, for the automatic
      generation of candidate structures conforming to the requirements of a given
      pharmacophore. The treatment consists in connecting the pharmacophoric pieces
      with spacers assembled from small chemical entities (atoms, chains, or ring
      moieties). We have tested the program on several sets of input fragments, each
      comprising selected functional groups obtained from the bioactive conformations
      of reference molecules. In addition to the expected solutions, the program can
      generate new structures that are chemically unrelated to the reference molecules.
      This provides an unbiased starting point for the design of new generations of
      lead structures. The concept used in this approach is presented and discussed.
      The present possibilities of the program are illustrated by some examples. The
      treatment is very fast, because only a few bonds are created between building
      blocks already having ideal geometries. The ability to generate rapidly a variety
      of molecules conforming to a three-dimensional pharmacophoric model makes NEWLEAD
      a useful tool with wide applicability in rational drug design, including the
      areas of molecular mimicry and peptidomimetism.

PMID- 8254619
TI  - Nonprostanoid prostacyclin mimetics. 4. Derivatives of 2-[3-[2-(4,5-diphenyl-2
      oxazolyl)ethyl]phenoxy]acetic acid substituted alpha to the oxazole ring.
AB  - The 4,5-diphenyloxazole derivatives 2-4 were previously identified as
      nonprostanoid prostacyclin (PGI2) mimetics. A series of derivatives of 2-4
      bearing substitutents at the carbon atom alpha to the oxazole ring were
      synthesized and evaluated as inhibitors of ADP-induced aggregation of human
      platelets in vitro. In the unsaturated series, the alpha-carbethoxy derivative
      10a, evaluated as an equal mixture of geometrical isomers, inhibited platelet
      aggregation with an IC50 of 0.36 microM. Evaluation of the individual methyl
      ester derivatives (E)-9a and (Z)-9a revealed that (E)-9a was 10-fold more potent
      than (Z)-9a. In the saturated series, the alpha-carbomethoxy-substituted compound
      12a inhibited platelet aggregation with an IC50 of 0.08 microM, 15-fold more
      potent than the unsubstituted prototype 2. The potency of 12a was found to be
      sensitive to variation of the methoxy moiety. The ethyl (12b) and isopropyl (12d)
      esters were less effective as were the acid 12e and a series of amides (12f-h).
      Other substituents introduced at this site of the pharmacophore included
      P(O)(OEt)2 (25), SCH3 (31a), S(O)CH3 (31b), SO2CH3 (31c), isopropyl (31d), phenyl
      (31f), and CH2OH (31i). However, none were significantly more potent inhibitors
      of platelet function than the parent compound 2. The results indicate the
      presence of a pocket in the PGI2 receptor protein that preferentially recognizes
      small, polar but uncharged substituents. The structure-activity correlates are
      suggestive of a hydrogen-bond interaction between a donor moiety on the PGI2
      receptor and the methoxycarbonyl functionality of 12a that is sensitive to both
      the size of the substituent and its stereochemical presentation in this
      structural class of PGI2 mimetic. The ethyl ester 12b dose-dependently displaced
      [3H]iloprost from human platelet membranes and stimulated adenylate cyclase.
      However, the maximal stimulation was less than that recorded for iloprost,
      indicating that 12b functions as a partial agonist at the PGI2 receptor.

PMID- 8254620
TI  - 3,4-Dihydroxychalcones as potent 5-lipoxygenase and cyclooxygenase inhibitors.
AB  - A novel series of 3,4-dihydroxychalcones was synthesized to evaluate their
      effects against 5-lipoxygenase and cyclooxygenase. Almost all compounds exhibited
      potent inhibitory effects on 5-lipoxygenase with antioxidative effects, and some
      also inhibited cyclooxygenase. The 2',5'-disubstituted 3,4-dihydroxychalcones
      with hydroxy or alkoxy groups exhibited optimal inhibition of cyclooxygenase. We
      found that 2',5'-dimethoxy-3,4-dihydroxychalcone (37; HX-0836) inhibited
      cyclooxygenase to the same degree as flufenamic acid and 5-lipoxygenase, more
      than quercetin. Finally, these active inhibitors of 5-lipoxygenase inhibited
      arachidonic acid-induced mouse ear edema more than phenidone.

PMID- 8254621
TI  - Molecular structures, conformational analysis, and preferential modes of binding
      of 3-aroyl-2-arylbenzo[b]thiophene estrogen receptor ligands: LY117018 and aryl
      azide photoaffinity labeling analogs.
AB  - Structural and computational modeling studies were performed on the antiestrogen
      LY117018 (3) and two photoaffinity labeling analogs, in which an azide replaces
      the basic ether side chain (methyl ether tetrafluoro azide 7 and its protio
      analog 8). These studies were undertaken in order to determine the conformational
      preferences of these compounds and to propose favorable orientational modes for
      their binding to the estrogen receptor. In the crystallographic studies, we found
      that, unlike tetrafluoro azide 7, which adopts a face-to-face stacking of the p
      hydroxyphenyl and benzoyl groups in the solid state, the pendant rings in the
      corresponding protio analog 8 are found in a predominantly offset pi-stacked
      array. In LY117018, which has an ether on the benzoyl ring, stacking of the
      pendant rings does not occur in the crystal structure; it assumes a T-shape, with
      the benzoyl group oriented perpendicular to the benzo[b]thiophene nucleus. In
      modeling studies, analogs of LY117018, 7, and 8 were subjected to a
      conformational grid search by molecular mechanics, and for each compound, three
      low-energy conformers (and their atropisomers) were obtained. These conformers
      were further geometry optimized by semiempirical molecular orbital calculations.
      For each compound, one of the three minimum-energy conformers is quite similar to
      the solid-state geometry. The computational structure of the tetrafluoro azide
      showed the greatest stacking between the benzoyl group and the p-methoxyphenyl
      ring, but less stacking than was observed in the crystallographic structure. The
      orientational preferences of these benzo[b]thiophene ligands with the estrogen
      receptor were analyzed with the receptor volume mapping technique, a method based
      on the correspondence of the hydroxyl groups and the volume that the
      benzo[b]thiophene compound shares with a composite molecular volume of high
      affinity estradiol-type ligands (the receptor excluded volume, RExV). If the
      benzo[b]thiophene nucleus is overlapped with the steroid AB rings, the best
      overlap with the RExV is achieved, but there is poor correspondence of the
      hydroxyl groups. An orientation and conformation in which the benzoyl group of
      the 3-benzoyl-2-aryl-benzo[b]thiophenes occupies a 7 alpha-like position relative
      to the steroid produces both ample volume overlap with the RExV and close
      approximation of the hydroxyl groups and is presented as the putative bioactive
      conformation.

PMID- 8254623
TI  - Syntheses of 2,5- and 2,6-difluoronorepinephrine, 2,5-difluoroepinephrine, and
      2,6-difluorophenylephrine: effect of disubstitution with fluorine on adrenergic
      activity.
AB  - Synthetic routes to difluorinated analogs of the adrenergic agonists,
      norepinephrine (NE), epinephrine (E), and phenylephrine (PE) have been developed.
      The syntheses were based on elaboration of the ethanolamine side chains from the
      appropriately polyfunctionalized benzaldehydes. The benzaldehydes were prepared
      from precursor difluorinated benzenes by sequential regioselective lithiations
      and reaction with electrophiles to introduce hydroxyl and carboxaldehyde
      functionalities. Binding and functional assay data demonstrate that the 2,6
      difluorinated analogs are relatively inactive at both alpha- and beta-adrenergic
      receptors. These results are consistent with earlier observations that 2-fluoro
      substitution of adrenergic agonists decreases alpha-adrenergic activity whereas 6
      fluoro substitution decreases beta-adrenergic activity.

PMID- 8254622
TI  - Identification of potent, selective P2Y-purinoceptor agonists: structure-activity
      relationships for 2-thioether derivatives of adenosine 5'-triphosphate.
AB  - Study of P2-purinoceptor subtypes has been difficult due to the lack of potent
      and selective ligands. With the goal of developing high affinity P2-purinoceptor
      selective agonist, we have synthesized a series of analogues of adenine
      nucleotides modified on the purine ring as chain-extended 2-thioethers or as N6
      methyl-substituted compounds. Chemical functionality incorporated in the
      thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n
      alkyl, and olefinic groups. Apparent affinity of the compounds for P2Y
      purinoceptors was established by measurement of P2Y-purinoceptor-promoted
      phospholipase C activity in turkey erythrocyte membranes and relaxation of
      carbachol-contracted smooth muscle in three different preparations (guinea pig
      taenia coli, rabbit aorta, and rabbit mesenteric artery). Activity at P2X
      purinoceptors was established by measurement of contraction of rabbit saphenous
      artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2
      thioethers of ATP stimulated the production of inositol phosphates with K0.5
      values of 1.5-770 nM, with an (aminophenyl)ethyl derivative being most potent.
      Two adenosine diphosphate analogues were equipotent to the corresponding ATP
      analogues. Adenosine monophosphate analogues were full agonists, although
      generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD2
      values in the range of 6-8 in smooth muscle assay systems for activity at P2Y
      receptors. There was a significant correlation for the 2-thioether compounds
      between the pK0.5 values for inositol phosphate production and the pD2 values for
      relaxation mediated via the P2Y-purinoceptors in the guinea pig taenia coli, but
      not for the vascular P2Y-receptors or for the P2X-receptors. At P2X-receptors, no
      activity was observed in the rabbit saphenous artery, but variable degrees of
      activity were observed in the guinea pig vas deferens and bladder depending on
      distal substituents of the thioether moiety. N6-Methyl-ATP was inactive at P2X
      receptors, and approximately equipotent to ATP at taenia coil P2Y-receptors. This
      suggested that hybrid N6-methyl and 2-thioether ATP derivatives might be potent
      and selective for certain P2Y-receptors, as was shown for one such derivative, N6
      methyl-2-(5-hexenylthio)-ATP.

PMID- 8254624
TI  - Neurosteroid analogues: structure-activity studies of benz[e]indene modulators of
      GABAA receptor function. 1. The effect of 6-methyl substitution on the
      electrophysiological activity of 7-substituted benz[e]indene-3-carbonitriles.
AB  - The effect of 6-methyl substitution of the ability of 7-(2
      hydroxyethyl)benz[e]indene-3-carbonitriles to potentiate GABA-mediated chloride
      current and to directly gate a chloride current in the absence of GABA in
      cultured rat hippocampal neurons was investigated. Structurally analogous steroid
      17-carbonitriles that either contained or did not contain a 19-methyl group were
      also investigated. Compounds were evaluated at 1 microM for their ability to
      potentiate GABA-mediated currents and at 10 microM for current activation in the
      absence of GABA. The benz[e]indene 3(R)-carbonitriles and analogous steroid 17
      alpha-carbonitriles had no effects in either assay. The benz[e]indene-3(S)
      carbonitriles and analogous steroid 17 alpha-carbonitriles were active in both
      assays. Relative to the 6-unsubstituted benz[e]indene 3(S)-carbonitrile, the
      following effects of 6-methyl substituents were observed: a 6(a)-methyl group
      increased both activities; a 6(e)-methyl group decreased both activities; and 6,6
      dimethyl substituents had opposing effects so that both activities remained
      similar to those of the 6-unsubstituted compound. The activities of the steroid
      17 beta-carbonitriles were not affected significantly by the presence or absence
      of a 19-methyl group. A conformational analysis using molecular modeling methods
      was also performed for the benz[e]indene 3S-carbonitriles and the steroid 17 beta
      carbonitriles. The ability of the different 6-methyl substituents to
      differentially effect the conformations of the flexible benz[e]indenes and the
      inability of the steroid 19-methyl group to alter the conformations of the rigid
      steroid 17 beta-carbonitriles are suggested to explain the results.

PMID- 8254625
TI  - New analogues of N-(2-aminoethyl)-4-chlorobenzamide (Ro 16-6491). Some of the
      most potent monoamine oxidase-B inactivators.
AB  - A series of halo- and nitro-substituted analogues of N-(2-aminoethyl)benzamide
      has been synthesized. All of the compounds are competitive, time-dependent
      inhibitors of monoamine oxidase-B (MAO-B), but upon dialysis complete return of
      enzyme activity is observed for all compounds. Therefore, these are mechanism
      based reversible inhibitors of MAO-B. The relative potencies of the compounds are
      rationalized in terms of steric and hydrophobic effects.

PMID- 8254626
TI  - Cardioselective anti-ischemic ATP-sensitive potassium channel openers.

PMID- 8254627
TI  - Methoxylation of cocaine reduces binding affinity and produces compounds of
      differential binding and dopamine uptake inhibitory activity: discovery of a weak
      cocaine "antagonist".

PMID- 8254628
TI  - Biphenylyl-substituted xanthones: highly potent leukotriene B4 receptor
      antagonists.

PMID- 8254629
TI  - Development of baits for tsetse flies (Diptera: Glossinidae) in Zimbabwe.
AB  - Analysis of host-oriented behavior of tsetse flies, Glossina morsitans morsitans
      Westw. and G. pallidipes Austen, led to a 10- to 1,000-fold improvement in the
      cost effectiveness of baits for surveys and control. Baits now are used widely to
      replace air and ground broadcasting of insecticides. Principles of behavioral
      analysis are discussed, with emphasis on the need to: confirm that the
      measurements made are the measurements required; assess the probability of flies
      executing single specific actions in response to each component of the overall
      stimulus from baits; count not only the flies that do one thing, but also the
      number that do the alternative(s); and use objective sampling devices of measured
      efficiency. The relevance to research with other flies is considered. The need
      for new tools to study continuously the field behavior of individual flies is
      stressed.

PMID- 8254630
TI  - New version of LSTSIM for computer simulation of Amblyomma americanum (Acari:
      Ixodidae) population dynamics.
AB  - A previous version of Lone Star Tick Simulation Model (LSTSIM) for a wildlife
      ecosystem was revised and expanded to include a beef cattle forage area and
      improved handling of tick-host-habitat interactions. Relationships between
      environmental and biological variables were also refined in the new version.
      General validity of the revised model was established by comparing simulated and
      observed host-seeking populations of Amblyomma americanum (L.) at five geographic
      locations, three in Oklahoma and two in Kentucky-Tennessee. Additional validity
      was indicated from comparisons of simulated and observed seasonality of lone star
      ticks at one location in Kentucky. The model produced acceptable values for
      initial population growth rate, generation time, and 15-yr population density
      when historical weather files for 14 locations in the United States were used.
      The model of A. americanum population dynamics was used to study the relationship
      between tick density and density of white-tailed deer, Odocoileus virginianus
      (Zimmerman), and cattle. The revised model can be used for additional simulation
      studies on effects of tick control technologies and integrated management
      strategies.

PMID- 8254631
TI  - Increasing density and Borrelia burgdorferi infection of deer-infesting Ixodes
      dammini (Acari: Ixodidae) in Maryland.
AB  - A statewide survey of Ixodes dammini Spielman was done in November 1991 as a
      follow-up to a study in 1989. In total, 3,434 adult ticks were collected from 922
      hunter-killed white-tailed deer processed at 22 check stations (1 per county in
      22 of 23 counties in the state). Significantly more male than female ticks were
      collected. Tick infestation was significantly heavier on male than female deer.
      The pattern of tick distribution was similar to that in 1989, with low prevalence
      (percentage tick-infested deer) and abundance (mean ticks per deer) in the
      Appalachian region, moderate values in the Piedmont, and high values in the
      western and eastern Coastal Plains regions. The pattern of tick infection with
      Borrelia burgdorferi spirochetes (determined by polyclonal immunofluorescence
      assay) was similar to the tick distributional pattern. Overall, tick prevalence
      and abundance were higher in 1991 than in 1989, as was the spirochete infection
      rate in ticks. Multiple regression analysis of tick prevalence against six
      selected physical and biotic parameters (elevation, rainfall, summer and winter
      temperature, percentage of forest land, deer density) showed a significant
      relationship with rainfall and elevation in 1989 and elevation alone in 1991. A
      more extensive study in Caroline and Dorchester counties in the eastern Coastal
      Plains region (which showed exceptionally low tick density indices in a generally
      tick-abundant region in 1989) demonstrated that I. dammini was well established
      in Caroline but not in Dorchester County.

PMID- 8254632
TI  - Relationships among body size, blood meal size, egg volume, and egg production of
      Tabanus fuscicostatus (Diptera: Tabanidae).
AB  - Number of ovarioles, egg production, and weight of unfed and bloodfed Tabanus
      fuscicostatus Hine females were related linearly to wing length. Wing length did
      not change whether flies were freshly thawed, preserved in formalin solution, or
      oven dried. Left and right wings were similar in length. The length from the
      costa to the anterior cross vein or to the intersection of R4 and R5 veins was
      associated linearly to wing length. The number of eggs produced by flies bloodfed
      on one or two bovine hosts was similar when adjusted by wing length. The average
      number of ovarioles per female was 277 +/- 50 (+/- SD), and eggs developed in
      only 63% of the ovarioles after a bloodmeal. An estimated 3.1 eggs were produced
      for each milligram of blood ingested by a fly, and the average bloodmeal size was
      110% of the unfed weight of the flies (49.7 mg). Egg volume was unrelated to body
      size, but was associated inversely with the number of eggs produced per female.

PMID- 8254633
TI  - Solar-powered electrocuting trap for controlling house flies and stable flies
      (Diptera: Muscidae).
AB  - A portable trap was constructed that was visually attractive to house flies,
      Musca domestica L., and stable flies, Stomoxys calcitrans (L.), outdoors. The
      trap was made of a white and yellow pyramid placed on top of a white vertical
      base that had large cutouts in each side. Attracted flies were killed by means of
      solar-powered electrocuting grids. Three traps killed an average of 1,360 house
      flies and 1,190 stable flies per day at a manure dump and were effective in
      attracting flies under both cool (< 23 degrees C) and warm (> 30 degrees C)
      temperatures. Both species of flies were most attracted to the eastern side of
      the trap, but house flies preferred yellow in cool mornings and white in warm
      afternoons. When air temperatures were > 30 degrees C, both house flies and
      stable flies went into the shaded base of the trap or into tunnels. Most house
      flies were killed on the pyramidal top of the trap, whereas most stable flies
      were killed on the vertical base. Opaque fiberglass tunnels with central
      electrocuting grids were simpler and cheaper, although less effective, for stable
      flies.

PMID- 8254634
TI  - Activity of Culicoides furens larvae (Diptera: Ceratopogonidae) as related to
      light and nutritional state.
AB  - The diel activity of fourth-instar Culicoides furens (Poey) was studied in the
      laboratory by means of video recordings. Larvae in 0.5% agar under a photoperiod
      of 12:12 (L:D) h were observed under three nutritional states: starved 24 h
      before and during observation; fed (with nematodes) 24 h before, but starved
      during, observation; and fed both before and during observation. Starved larvae
      displayed considerably reduced activity compared with those that were better fed,
      both in terms of speed and type of movement (the proportion of time spent in
      continuous rather than intermittent motion). Under all nutritional states, larvae
      were more active during dark than light hours; 3-hourly observations of speed
      plotted for four periods of 24 h strongly indicated a diel cycle of activity,
      which may, in the field, be accompanied by vertical migration in the soil.
      Overall, our observations indicated that during development, C. furens larvae
      rove constantly through the substrate, at speeds of approximately 2 m/h (and up
      to 4 m/h), and that this movement is maintained even in the presence of abundant
      food.

PMID- 8254635
TI  - Seasonal abundance, age composition, and body size of salt-marsh Anopheles
      (Diptera: Culicidae) in south Florida.
AB  - Five CO2-baited light traps operated fortnightly between November 1989 and May
      1991 near a salt marsh in Vero Beach, FL, caught 1,961 Anopheles crucians
      Wiedemann (s.l.) and 691 An. atropos Dyar & Knab. Both species were most abundant
      in winter and least abundant in summer; their numbers correlated inversely with
      lagged mean ambient temperatures. Annual parous rates were 55% for An. crucians
      and 58% for An. atropos and varied little seasonally. Wing lengths of female An.
      crucians measured for eight consecutive months were negatively correlated with
      ambient temperatures, and parous females of this species had significantly longer
      wings than nullipars. Parous rates and wing length classes were positively
      correlated among An. crucians, confirming that larger mosquitoes are longer
      lived.

PMID- 8254636
TI  - Seasonal abundance of stable flies and house flies (Diptera: Muscidae) in dairies
      in Alberta, Canada.
AB  - Seasonal abundance of stable flies and house flies was studied at four dairies in
      southern Alberta, Canada, from May to October in 1989, 1990, and 1991. Stable
      flies were active from May to October in all years and showed population peaks in
      August and September. The weekly rate of change of stable fly populations was
      influenced by temperature and accumulated degree-days above 10 degrees C. The
      weekly rate of change of stable fly populations showed four peaks which were
      attributed to the emergence of an initial generation which had overwintered,
      followed by an additional three generations. Stable fly attacks on dairy cows
      occurred mainly from July through October, corresponding with the last two
      generations. House fly population abundance was much lower than stable fly
      populations and showed peaks in June, July, and September. Weekly changes in
      house fly abundance were not influenced by temperature and only weakly influenced
      by accumulated degree-days above 10 degrees C. Peaks in the weekly rate of change
      were associated with emergence of an initial, overwintering generation followed
      by four generations produced throughout the summer.

PMID- 8254637
TI  - Ticks (Acari: Ixodidae) infesting medium-sized wild mammals in southwestern
      Tennessee.
AB  - Seven species of ixodid ticks (n = 2,661) were found on medium-sized wild mammals
      (n = 295) during a 13-mo study in Shelby County, Tennessee. The seven tick
      species collected were Dermacentor variabilis (Say), Amblyomma americanum (L.),
      Rhipicephalus sanguineus (Latreille), Ixodes texanus (Banks), I. cookei
      (Packard), I. scapularis (Say), and Haemaphysalis leporispalustris (Packard). The
      raccoon had the greatest tick species diversity in all of the aforementioned
      ticks except H. leporispalustris and R. sanguineus. The raccoon and opossum
      accounted for 96.9% of the ticks collected and were the most commonly captured
      medium-sized mammals. The only tick collected in high enough numbers for
      statistical analysis was D. variabilis. Mammal species and habitat type were the
      most important factors affecting the mean number of adult D. variabilis per
      mammal. The mean number of D. variabilis adults carried by raccoons was
      significantly higher than opossums. Whether a habitat occurred within Memphis
      city limits or outside city limits also affected the number of adult D.
      variabilis on mammals. The interaction between habitat, mammal, and whether
      inside or outside the city limits was near statistical significance. It is
      suggested that there is biological significance; within city limits, medium-sized
      wild mammals are forced into wooded areas where there is a subsequent increase in
      tick populations in these habitat patches.

PMID- 8254638
TI  - Development of a trap for collecting newly emerged Ctenocephalides felis
      (Siphonaptera: Pulicidae) in homes.
AB  - The visible light spectra most attractive to cat fleas, Ctenocephalides felis
      (Bouche), were determined. A green-yellow filter with a transmittance spectrum
      centered at 515-nm and a 82.5-nm half-height width attracted significantly more
      fleas than any other filter or white light. This information and observations on
      this flea's behavior were used to design a trap with a green-yellow filter and a
      light source with a 10-min:5-s (on and off) cycle. This trap collected > 86% of
      the live fleas released into a carpeted room (3.1 by 3.3 m) during a 20-h test
      period, whereas each of three commercially available flea traps collected
      approximately 13% of the fleas. Fleas < 1 d after emergence were not as
      responsive to the traps as older fleas. During 20-h testing periods, this new
      trap caught > 57% of the fleas released 8.4 m from the trap.

PMID- 8254639
TI  - Age- and sex-related effects in German cockroaches fed an allopurinol diet
      (Dictyoptera: Blattellidae).
AB  - The effects of feeding several ages of adult and nymphal German cockroaches a
      laboratory rat chow diet containing 0.10% allopurinol were investigated. All
      cockroaches fed the allopurinol diet suffered increased mortality. The range of
      LT50 values (the time required to kill 50% of an experimental cohort) for four
      ages of nymphs (1-8, 16-23, 21-28, and 28-35 d old following hatch) continuously
      fed the allopurinol diet was 1.36 wk (4.72-6.08 wk). Regardless of sex, young
      adult (1-7 d old following eclosion) cockroaches fed the allopurinol diet died
      significantly sooner than older adults (28-35 d old following eclosion); males
      died significantly sooner than females. All females fed the allopurinol diet as
      nymphs aborted their oothecae. Although an initial ootheca were hatched from
      cockroaches fed the allopurinol diet as adults, all subsequent oothecae were
      aborted. Untreated females mated with allopurinol-fed males experienced
      successful reproduction, but allopurinol-fed females mated with either
      allopurinol- or control diet-fed males failed to reproduce. Evidence suggests
      that cockroaches suffer increased mortality and reproductive failure from
      increased levels of hypoxanthine and xanthine.

PMID- 8254640
TI  - Rapid cold-hardening in Culicoides variipennis sonorensis (Diptera:
      Ceratopogonidae).
AB  - Rapid cold-hardening was studied in the adult stage of the biting midge
      Culicoides variipennis sonorensis Wirth & Jones from a laboratory colony. No
      individuals could withstand a direct transfer from 20 degrees C (rearing
      temperature) to -10 degrees C for 2 h; however, an acclimation period of 1 h at 5
      degrees C immediately before exposure to -10 degrees C yielded 96% survival. The
      cold-hardening response was very rapid; increased cold tolerance peaked after
      only a 1-h exposure to 5 degrees C. No fly withstood 2 h at -20 degrees C,
      demonstrating the limitations of the cold-hardening response. Varying degrees of
      cold tolerance also were induced by a 2-h exposure to 37 degrees C. The ability
      to rapidly cold-harden varied with the age of the adult insect. Rapid cold
      hardening in adult C. v. sonorensis may be of ecological and epizootiological
      significance because it is a mechanism by which a nondiapausing life stage
      quickly can enhance its tolerance to subzero temperatures.

PMID- 8254641
TI  - Trypanosome transmission by Corethrella wirthi (Diptera: Chaoboridae) to the
      green treefrog, Hyla cinerea (Anura: Hylidae).
AB  - Seventy-two percent of 215 male green tree frog, Hyla cinerea (Schneider),
      captured in Alachua and Levy counties, FL, between April and mid-September 1978
      and 1979 were infected with an undescribed Trypanosoma sp. None of the 31 female
      frogs captured concurrently was infected. Periodic sampling of the peripheral
      blood from the infected male frogs showed that the trypanosomes were present in
      high numbers only at night. Conspecific trypanosomes also were found in the mid
      and hind guts of female Corethrella wirthi Stone flies collected on or near male
      frogs in the field. Transmission of the parasite to uninfected frogs was
      demonstrated by exposure of male and female frogs to naturally infected flies and
      to parasites injected subdermally. This is the first report of parasite
      transmission by a species of Corethrella.

PMID- 8254642
TI  - Blood-feeding patterns of Aedes aegypti (Diptera: Culicidae) collected in a rural
      Thai village.
AB  - Aedes aegypti (L.) were collected by aspiration once each week from in and around
      houses in a rural village in Chachoengsao Province. Thailand, during May 1990 to
      June 1991. Of the 1,230 specimens analyzed with a sandwich ELISA, 73% reacted to
      one or more of the seven hosts which we tested. Eighty-eight percent (789/896) of
      all detectable meals were identified as being from a single host (human). Patent
      multiple meals (double and triple), of which one was always human, were detected
      in 7% (66/896) of the specimens. The probability of feeding on a human, either as
      a single host or in a patent mixed meal, was > 0.90 during 12 of the 14 mo of the
      study; this probability never dropped below 0.85. The probability of Ae. aegypti
      taking multiple blood meals during a single gonotrophic cycle varied widely from
      0.0 to 1.0. The possibility is discussed, including epidemiological significance,
      that there are seasonal fluctuations in the frequency of multiple feeding by Ae.
      aegypti and that multiple feeding increases in concert with seasonal trends for
      dengue infections of humans in Thailand.

PMID- 8254643
TI  - Modulation of murine immunological responses by salivary gland extract of
      Simulium vittatum (Diptera: Simuliidae).
AB  - The influence of Simulium vittatum Zetterstedt salivary gland extract on several
      immunological mechanisms was investigated in murine model hosts (laboratory
      mice). These mechanisms included the expression of major histocompatibility
      complex class II cell surface molecules, the in vitro mitogen responsiveness of
      lymphoid cells, and the antibody responses to heterologous foreign antigens
      (sheep erythrocytes). Experiments were designed to determine the influence of
      salivary gland extract following in vivo inoculation or in vitro inclusion in
      cell culture. In vivo inoculation of salivary gland extract reduced the
      percentage of Ia+ cells in spleen cell populations, although this difference was
      ameliorated by a 2 d in vitro culture period, regardless of whether salivary
      gland extract was included in culture. Salivary gland extract had no effect on Ia
      expression by cells derived from regional lymph nodes or the skin (epidermis). In
      vivo inoculation with salivary gland extract did not affect the responsiveness of
      splenic lymphocytes to mitogens, whereas in vitro exposure to salivary gland
      extract reduced both T and B cell mitogenesis. Finally, antibody responses to
      sheep erythrocytes were enhanced if salivary gland extract was included as a
      coinoculant, although this was expressed only at the systemic level regardless of
      the route of antigen delivery. In light of these results, immunomodulatory
      functions of black fly saliva are postulated; they are operative at different
      levels on different subcompartments of the immune system, possibly via cytokine
      modulation.

PMID- 8254644
TI  - Importance of low dispersion of Anopheles gambiae (Diptera: Culicidae) on malaria
      transmission in hilly towns in south Cameroon.
AB  - The dispersion of Anopheles gambiae Giles s.l. from larval breeding places was
      examined in the towns of Yaounde and Edea, Cameroon. The study areas are
      characterized by hilly reliefs of approximately 40 m and by larval breeding
      places in the swampy valleys. Mosquito density was estimated by night-biting
      indoor catches carried out during 1 yr in three districts, with four collecting
      houses in each, along a transect from 0 (at the valley bottom) to 350 m (at the
      hilltop). In each district, the human-biting rate decreased gradually from valley
      bottom to hilltop. In two districts, the observed densities were zero at 200 and
      250 m from breeding places. In the third district where the habitat is less
      dense, there was a 50% reduction in biting mosquitoes at 350 m from valley
      bottom. Our studies confirm that dense habitat in the urban area is associated
      with a low degree of vector dispersion. It emphasizes that slope is another
      factor which limits dispersion. These findings explain why malaria transmission
      is heterogenous (range, 0-45 infective bites per man per year) inside the
      districts and occurs mainly around swamps in the valleys. These data are
      important when considering the uncontrolled urbanization which is occurring in
      the undeveloped areas in the valleys.

PMID- 8254645
TI  - Sequence of a DNA probe specific for Anopheles quadrimaculatus species A
      (Diptera: Culicidae).
AB  - The nucleotide sequence was determined for a portion of a 12-kb genomic DNA clone
      specific for Anopheles quadrimaculatus species A. Four short, internally repeated
      sequences were identified. Synthetic oligonucleotide probes were prepared based
      on these four repeats. The oligonucleotides are highly specific and can be
      reliably used to separate individuals of An. quadrimaculatus species A from
      members of other species of the complex.

PMID- 8254646
TI  - Laboratory demonstration of oviposition by Aedes aegypti (Diptera: Culicidae) in
      covered water jars.
AB  - In Thailand, ceramic jars (135-200 liters) covered by aluminum lids commonly are
      used to store water for household use. In laboratory cages, gravid female Aedes
      aegypti (L.) were able to enter and oviposit in a covered water jar. Although the
      aluminum lid was not a complete barrier to gravid females, it reduced the number
      of eggs oviposited by 77%. A vertically oriented foam rubber ring which was
      compressed between the lip of the jar and the flange of the lid effectively
      sealed the jar against ovipositing mosquitoes.

PMID- 8254647
TI  - Ixodes dammini (Acari: Ixodidae) infestation on medium-sized mammals and blue
      jays in northwestern Illinois.
AB  - High prevalence of infestation of five species of medium-sized mammals and blue
      jays, Cyanocitta cristata (L.), by immature Ixodes dammini Spielman, Clifford,
      Piesman and Corwin was found in Castle Rock State Park in northwestern Illinois
      during May-August 1991. Raccoons, Procyon lotor L., and opossums, Didelphis
      virginiana Kerr, were infested with the highest larval densities and were trapped
      primarily in bottomland forest and ecotone habitats. All species had similar
      nymphal densities, except the eastern cottontails, Sylvilagus floridanus Allen,
      which were infested with fewer nymphs. Infestation by I. dammini is reported for
      the first time for fox squirrels, Sciurus niger E. G. St. Hilaire, and for the
      first time in the midwestern United States for blue jays, C. cristata. These two
      species were hosts for nymphs in upland forest habitat. Molting rates varied
      among ticks that fed on different host species and among larvae that fed on
      individuals of the same species. Molting rate is proposed as an important factor
      in determining the relative importance of a host species to I. dammini population
      dynamics.

PMID- 8254648
TI  - Evaluation of the polymerase chain reaction method for identifying members of the
      Anopheles gambiae (Diptera: Culicidae) complex in southern Africa.
AB  - Chromosomally and electrophoretically identified field samples of members of the
      Anopheles gambiae Giles complex from southern Africa and colony material were
      used to test the polymerase chain reaction (PCR) method of identification. The
      samples included An. arabiensis Patton, An. quadriannulatus Theobald, and An.
      merus Donitz. Only one of the 217 specimens examined was disputed. Twenty
      specimens (9%) were reamplified because of the presence of multiple bands or lack
      of amplification after the first assay. Specimens of An. merus from this region
      displayed both the diagnostic An. merus PCR band as well as the An.
      quadriannulatus band, possibly because of interspecific hybridization or random
      variation within the population. This work extends the geographical range over
      which the PCR technique has been verified to southern Africa.

PMID- 8254649
TI  - Personal changes, dispositional optimism, and psychological adjustment to bone
      marrow transplantation.
AB  - We investigated the number and direction of personal changes experienced by long
      term survivors of bone marrow transplantation (BMT) and the relationships of
      those changes and dispositional optimism to psychological adjustment (current and
      future life satisfaction and mood). Surveys were returned by 86.0% (N = 135) of
      all eligible long-term survivors; respondents primarily were young males who were
      6 to 149 months post-BMT. Subjects reported more positive changes in the
      relationship and existential/psychological domains and more negative changes in
      the physical health domain; there was no difference on the plans/activities
      domain. Negative changes were more strongly related to adjustment than were
      positive changes. The number of negative changes reported was significantly
      related to current and future life satisfaction and negative mood after
      controlling for demographic and illness variables and dispositional optimism. The
      interaction term for negative and positive changes was significantly related to
      future life satisfaction after controlling for all other variables.

PMID- 8254650
TI  - Psychological, situational, and gender predictors of cardiovascular reactivity to
      stress: a multivariate approach.
AB  - This study examined whether relationships between anger expression, hostility,
      social evaluative anxiety, and a presumed mechanism for coronary heart disease
      development, cardiovascular reactivity (CVR) to stress, are moderated by stress
      situation and gender and whether such relationships are attenuated by inadequate
      assessments. Subjects (47 men, 47 women) were assigned randomly to either a
      Harassment or a Social Evaluation condition, under which they performed a
      reaction time task. SBP, DBP, and HR measures were recorded during baseline and
      task. Multiple regression analyses indicated that expressed anger was related to
      CVR only among men in the Harassment condition; that hostile men who express
      anger showed the most CVR across situations, and that the traits assessed here
      did not predict CVR among women. Results suggest that assessments of coronary
      risk and interventions to reduce risk may need to take into account attitudes,
      styles of emotional expression, environmental factors, and gender.

PMID- 8254651
TI  - Minnesota Multiphasic Personality Inventory (MMPI) cluster groups among
      chronically ill patients: relationship to illness adjustment and treatment
      outcome.
AB  - Cluster analysis of the MMPI has been utilized widely in the chronic low back
      pain literature to try to identify reliable patient subtypes predictive of
      treatment outcome. We extended this methodology to patients with heterogeneous
      chronic medical conditions by replicating prototypic MMPI cluster group profiles
      and by relating cluster groups to clinical baseline and outcome data. Subjects
      were two independent samples (n = 254 and n = 263) of chronically ill patients
      admitted to an inpatient medicine/psychiatry unit. Using a four-cluster solution,
      similar cluster profile groups were replicated in both samples. Consistent
      differences emerged between cluster groups on functional impairment, psychiatric
      diagnoses, depression, and psychosomatic symptoms. Cluster group membership also
      predicted changes in functional impairment and depression six months after
      treatment. Results are discussed in terms of similarities between chronic low
      back pain and chronic illness and tailoring treatment to different patient types.

PMID- 8254652
TI  - Cancer stereotypes: a multidimensional scaling analysis.
AB  - The body of empirical research investigating the structure of stereotypes held by
      the physically healthy population toward individuals with medically related
      problems is remarkably small. This is particularly true for stereotypes related
      to cancer. This study adopted a multidimensional scaling (MDS) strategy in order
      to identify medically related stereotype dimensions for cancer and other
      illnesses. Sixty-eight subjects judged the similarity of cancer and eleven other
      medical conditions and rated each on 7-point attribute scales. A two-dimensional
      solution of respondents' similarity judgments was found and four distinct
      clusters of related conditions were perceived: (1) cancer and other illnesses
      with controllable risk factors, (2) conditions affecting motor function, (3)
      psychological/functional disorders and (4) communication/sensory functional
      disorders. Regression of mean attribute ratings onto the MDS disability
      coordinates labeled the two dimensions Normality and Physical Health.
      Implications of these dimensions for planning effective programs to change
      stereotypes and improve attitudes toward individuals with cancer and other
      medical conditions are discussed.

PMID- 8254653
TI  - Cognitive representations of bodily parts and products: implications for health
      behavior.
AB  - This study investigated the unexplored hypothesis that people may have cognitive
      representations of the body's parts and products (body schema) and that these may
      be relevant to illness behavior. Factor and MANOVA analyses revealed that body
      parts are viewed as differing in the Stigma attached to them and in the extent to
      which they are seen as Important, Vulnerable, Sexual, and Private, with these
      five dimensions found to be independent of age and health history. Seeking help
      for dysfunction varied across body parts, with subjects reluctant to seek help
      for highly stigmatized and private parts but likely to seek help for parts viewed
      as important and vulnerable. Significant gender and ethnic differences in
      representations of body parts also emerged.

PMID- 8254654
TI  - Prediction of adherence and control in diabetes.
AB  - This study aims to predict adherence to diabetic treatment regimens and sustained
      diabetic control. During two clinic visits that were 2 months apart, 63 adult
      outpatients completed measures of diabetic history, current treatment, diabetic
      control, adherence, and self-efficacy about adherence to treatment. Results
      showed that self-efficacy was a significant predictor of later adherence to
      diabetes treatment even after past levels of adherence were taken into account.
      Posttest levels of adherence in turn were significantly associated with posttest
      %HbA1c after control for illness severity. A stepwise multiple regression to
      predict %HbA1c at post entered pretest measures of diabetic control, treatment
      type, and self-efficacy, which together predicted 50% of the variance. Results
      are related to self-efficacy theory and implications for practice are discussed.

PMID- 8254655
TI  - Measurement of the Type A behavior pattern from adolescence through midlife:
      further development of the adolescent/adult Type A behavior scale (AATABS).
AB  - We reported in 1990 the development of the Adolescent/Adult Type A Behavior Scale
      (AATABS). While the measure showed considerable promise, improvements to its
      component structure were indicated. The present study reports such modifications
      and also provides data on the use of the new scale, the AATABS-R, with middle
      aged subjects as well as young adults from the United States.

PMID- 8254656
TI  - Computing the structure of bound peptides. Application to antigen recognition by
      class I major histocompatibility complex receptors.
AB  - The ability to accurately compute the atomic positions of substrate-bound ligands
      is central to understanding biological recognition. Although substantial progress
      has been made in docking small, relatively rigid ligands, the problem of docking
      flexible peptides remains open. In this communication we present a new method
      that allows configurational flexibility of peptides, and apply it to predict the
      conformation of peptides bound to two class-I major histocompatibility complex
      receptors: human HLA-A2, and murine H-2Kb. Using only the approximate locations
      of the amino and carboxyl-terminal residues of the bound peptide, our
      calculations yield structures with backbone conformations that are similar to
      structures reported crystallographically.

PMID- 8254657
TI  - Resolution of synthetic chi structures by the FLP site-specific recombinase.
AB  - The FLP site-specific recombinase is encoded by the two micron circle, an
      endogenous plasmid of Saccharomyces cerevisiae. FLP-mediated recombination in
      vitro proceeds via a short-lived Holliday (chi) intermediate. We have made a
      synthetic chi structure containing two FLP recognition target (FRT) sequences in
      order to investigate resolution by purified FLP protein. We found that incubation
      of this model substrate with FLP generated two pairs of linear products in equal
      quantities. Thus, resolution was equally likely to occur in either direction.
      Alteration of FLP binding sites, so as to inhibit binding, affected the direction
      of resolution; cleavage was reduced adjacent to the altered binding site. The
      overall efficiency of resolution increased when one FLP binding site was mutated.
      In investigating the series of mutated chi structures we found that resolution
      requires only two intact FLP binding sites. However, the non-specific protein-DNA
      interaction of additional FLP molecules may also be required. Thus, resolution is
      more tolerant of the loss of FLP binding sites than is the complete recombination
      reaction.

PMID- 8254658
TI  - The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by
      gyrase.
AB  - DNA topoisomerases perform essential roles in DNA replication, gene
      transcription, and chromosome segregation. Recently, we identified a new type of
      topoisomerase II poison: the CcdB protein of plasmid F. When its action is not
      prevented by CcdA protein, the CcdB protein is a potent cytotoxin. In this paper,
      using purified CcdB, CcdA and gyrase, we show that CcdB protein efficiently traps
      gyrase in a cleavable complex. The CcdA protein not only prevents the gyrase
      poisoning activity of CcdB but also reverses its effect on gyrase. The mechanism
      by which the CcdB protein induces DNA strand breakage is closely related to the
      action of quinolone antibiotics. However, the ATP dependence of the CcdB cleavage
      process differentiates the CcdB mechanism from quinolone-dependent reactions
      because the quinolone antibiotics stimulate efficient DNA breakage, whether or
      not ATP is present. We previously showed that bacteria resistant to quinolone
      antibiotics are sensitive to CcdB and vice versa. Elucidation of the mechanism of
      action of CcdB protein may permit the design of drugs targeting gyrase so as to
      take advantage of this new poisoning mechanism.

PMID- 8254659
TI  - Operator sequence context influences amino acid-base-pair interactions in 434
      repressor-operator complexes.
AB  - The 434 repressor binds more tightly to OR1 than it does to OR3. The repressor
      makes several specific contacts with the symmetrically arrayed outer four base
      pairs of the 14 base-pair site, and no specific contacts to the central six base
      pairs. The sequence of the outer base-pairs of OR1 and OR3 differs only by an A-
      >G substitution at position 4 in one half-site of OR3, while that of central
      bases is very different. As expected from sequence analysis of wild-type
      operators, the data show repressor prefers an A.T base-pair at position 4. The
      magnitude of this preference depends on operator sequence context and solution
      conditions. Position 4 changes in the context of OR1 have a greater effect on
      operator affinity for 434 repressor than do similar changes in OR3. Although OR1
      and OR3 display different affinities for 434 repressor, their repressor-operator
      complexes are similarly insensitive to changes in salt concentration and
      temperature. By contrast, complexes formed between repressor and position 4
      mutant OR1, bearing an A.T-->G.C change, and OR3, which bears a G.C-->A.T change,
      are affected greatly, and to similar extents, by changes in ionic strength and
      temperature. Nuclease protection experiments show that 434 repressor protects the
      DNA phosphate backbone of wild-type operators from cleavage more efficiently than
      those of mutant operators. These data show that the biochemical and structural
      properties of a repressor-operator complex, while affected by position 4 base
      sequence, are independent of the identity of this base. The ability of repressor
      to recognize the base at position 4 depends on the sequence context at operator
      positions 5 to 7. Apparently there is an interplay between the bases at operator
      positions 4 to 7 which has a global effect on the structure of the repressor
      operator complex.

PMID- 8254660
TI  - Affinity maturation of human growth hormone by monovalent phage display.
AB  - We describe a selection procedure for construction of very high affinity variants
      of human growth hormone (hGH) for binding to the extra cellular domain of its
      receptor (called the hGHbp). Five different libraries of mutated hGH genes (each
      containing approximately 2 x 10(5) protein variants) were created by randomly
      mutating four different codons at residues that were shown to be important for
      receptor binding by structural or functional criteria. Mutated proteins were
      displayed as single copies from their respective filamentous phagemid particles
      and sorted in vitro for binding to the immobilized hGHbp. Phagemid particles that
      bound the immobilized hGHbp were eluted and propagated. After three to seven
      rounds of binding enrichments, hGH variants were isolated that contained 2 to 4
      mutations and exhibited three- to sixfold improvements in binding affinity.
      Because of the limits of DNA transfection efficiency in creating the library we
      could not sample thoroughly mutations at more than four codons at once.
      Nonetheless, the free energy effects for these mutations acted cumulatively.
      Thus, by combining affinity enhanced mutants from libraries independently sorted
      we created an hGH variant with 15 substitutions that bound approximately 400-fold
      more tightly to the hGHbp than wild-type hGH. The affinity enhancements occurred
      predominantly by slowing the off-rate of the hormone (> 60-fold), and partly
      through increasing the on-rate (up to 4-fold). Residues that were shown to be
      important for binding by alanine-scanning were most highly conserved after
      binding selection, and interestingly many of them could be further improved.
      Thus, we found it most effective to randomly mutate the residues that were shown
      to modulate affinity by alanine-scanning, and to combine the selectants from
      separate libraries that exhibit the highest affinities. The selection procedure
      and mutagenesis strategy provides a framework for affinity maturation of protein
      protein complexes.

PMID- 8254661
TI  - Characterization of the Neisseria Iga beta-core. The essential unit for outer
      membrane targeting and extracellular protein secretion.
AB  - Extracellular transport of Neisseria IgA proteases across the bacterial outer
      membrane is accomplished by the translocation function contained within the C
      terminal Iga beta domain of IgA protease precursor proteins. Recently, we
      reported that Iga beta from N. gonorrhoeae MS11 (Val1097 to Phe1505), fused to a
      periplasmic passenger protein, facilitated its transport across the outer
      membrane, leading to surface exposure of the passenger. In the present work we
      show, by systematic N-terminal truncation of Iga beta, that the functional and
      structural unit, termed Iga beta-core, corresponds to the C-terminal
      approximately 274 amino acid residues (Ser1231 to Phe1505). This minimal region
      retains all the essential features necessary for the translocation of an N
      terminally attached passenger across the outer membrane of Escherichia coli, and
      for its own correct integration into the outer membrane, even in the absence of a
      passenger protein. The membrane-integrated Iga beta-core constitutes a conserved
      entity found in the C-terminal regions of Iga beta domains of different N.
      gonorrhoeae, N. meningitidis and Haemophilus influenzae strains. In contrast, the
      surface-exposed N termini of the Iga beta domains vary in size and sequence.
      Based on secondary structure predictions, the key structural feature of the core
      is a beta-barrel (amphipathic, antiparallel transmembrane beta-strands,
      interspersed by hairpin turns and loops) which is common to many integral outer
      membrane proteins of Gram-negative bacteria. We propose that the core has been
      conserved in evolution, to provide a selective outer membrane export channel for
      covalently attached polypeptides.

PMID- 8254662
TI  - The role of cosB, the binding site for terminase, the DNA packaging enzyme of
      bacteriophage lambda, in the nicking reaction.
AB  - cosB is the binding site for terminase, the DNA packaging enzyme of ai-12581mbda,
      and cosN is the adjacent site at which terminase gm-07228es staggered nicks to
      generate mature lambda DNA molecules. There are three binding sites (R3, R2 and
      R1) within cosB for gpNu1, the small subunit of terminase. A particular
      transition mutation of R1, known to weaken binding of gpNu1 to R1, has been
      introduced into the other R sites, and in the present work the effects of R site
      mutations on nicking of cosN have been examined. Nicking experiments performed in
      the presence of ATP suggest that the most profound cosB mutation tested (the R3
      R2-R1- mutation) would, at most, reduce cos nicking to congruent to 30% of the
      level observed for the wild-type substrate. In the presence of ATP, the R3-R2-R1-
      mutation had no significant effect on terminase nicking of the 1 strand and
      reduced r-strand nicking to 35% of the wild-type level. The other cosB mutations
      had no effect on the nicking of either DNA strand when nucleotide was added, but
      in the absence of ATP, most of the cos mutations resulted in some form of cosN
      nicking defect; the nicking defects, however, are milder than the in vivo
      packaging defects that result from the mutations. Quantitatively, only the effect
      of the R3-R2-R1- mutation on in vitro cosN nicking is reflective of the growth
      defect exhibited by a R3-R2-R1- phage but the nicking defect is only observed
      when ATP is omitted from the reaction. The proposal that the cosB mutations
      primarily affect DNA packaging rather than cosN nicking is discussed. All of the
      cosB mutations affect r-strand nicking to a greater extent than 1-strand nicking,
      implying that the interaction of terminase with the left half of cosN occurs via
      the direct recognition of cosNL by terminase. The level of DNA substrate required
      for half-maximal cos nicking is approximately equivalent for reactions performed
      in the presence or absence of ATP, indicating that ATP does not increase the
      affinity of terminase for cosB. ATP does accelerate the rate of cos nicking,
      suggesting that the role of ATP in promoting nicking of the cosB- DNAs is
      primarily to increase the rate of conversion of a cosN-terminase complex into
      product. A possible fourth R site, R4, is located on the other side of cosN from
      cosB.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254663
TI  - Synergism between Tat and VP16 in trans-activation of HIV-1 LTR.
AB  - When tethered to heterologous DNA both Tat and VP16 can activate transcription
      from the HIV-1 LTR. To determine if they act by similar mechanisms, we
      constructed several hybrid effectors between Tat or VP16 and DNA-binding domains
      of GAL4 or LexA proteins. We tested these effectors on substituted reporter
      targets, which contained one to six GAL4 or LexA DNA-binding sites placed
      upstream of the HIV-1 promoter. Whereas Tat acted very inefficiently via DNA even
      with five DNA-binding sites, effects of VP16 were observed with a single DNA
      binding site and increased with increasing number of sites. More importantly,
      effects of VP16 via DNA were synergistic with those of Tat via TAR RNA when both
      proteins were expressed simultaneously. We next created a tripartite fusion
      protein, which contained the GAL4 DNA-binding domain and activation domains of
      both Tat and VP16, which could be targeted to the HIV-1 LTR either via DNA or
      RNA. By introducing individual deleterious mutations into either Tat or VP16, we
      confirmed that effects of VP16 predominated via DNA whereas Tat but not VP16
      acted via TAR RNA. Thus, Tat and VP16 act at different steps of the transcription
      process and increase expression from the HIV-1 LTR by different mechanisms.

PMID- 8254664
TI  - The refined structure of bacteriophage MS2 at 2.8 A resolution.
AB  - Bacteriophage MS2 is an icosahedral virus with 180 copies of a coat protein
      forming a shell around a single-stranded RNA molecule. The coat protein subunits
      form a lattice with the triangulation number T = 3. The coat protein has a fold
      which is different from the fold of all other viral coat proteins so far known.
      It consists of a five-stranded beta sheet facing the inside of the particle, and
      a hairpin and two helices on the outside. The crystal structure has been refined
      at 2.8 A resolution. The final R-factor was 0.189 for reflections with F > 2
      sigma, and the root-mean-square deviation from idealized bond lengths and bond
      angles was 0.015 A and 2.9 degrees, respectively. The three chemically identical
      conformers A, B and C are largely similar. The B conformer has a unique
      conformation in one loop, which is involved in 5-fold interactions, while the A
      and C conformers, which are involved in the quasi-6-fold contacts, are similar
      throughout the structure. One cis-proline has been identified in the B conformer
      but the corresponding prolines in A and C are of the trans isomer. This residue
      is conserved within small RNA coliphages and it is proposed that this
      isomerization enables a less elongated loop (FG) around the 5-fold axis, thus
      creating a channel. The extensive dimer contact supports the idea of dimers as
      initial building blocks. An assembly pathway is proposed where five dimers
      converge into a pentamer and 12 pentamers are linked together with free dimers
      creating a complete particle.

PMID- 8254665
TI  - Thermodynamic studies of the collagen-like region of human subcomponent C1q. A
      water-containing structural model.
AB  - Thermal transitions of Clq were investigated by methods of differential scanning
      calorimetry, circular dichroism and fluorescence. The melting curves of Clq
      display two pronounced heat absorption peaks with enables determination of the
      thermodynamic parameters characterizing each transition. The low temperature peak
      was assigned to melting of the Clq collagenous part. Analysis of the data has
      revealed unusual, as compared with the monomeric collagen molecules,
      thermodynamic features of the Clq collagenous part: (1) higher thermal stability
      strongly dependent on pH; (2) less linear co-operative regions; and (3) a
      noticeable change in the partial specific heat capacity (delta Cp) in contrast to
      both the monomeric collagen and the collagen fibrils. This unusually large delta
      Cp value suggested a conclusion that the fibril-like endpiece of Clq may have a
      cavity filled with ice-like ordered water molecules.

PMID- 8254666
TI  - Affinity and specificity of serine endopeptidase-protein inhibitor interactions.
      Empirical free energy calculations based on X-ray crystallographic structures.
AB  - An empirical function was used to calculate free energy change (delta G) of
      complex formation between the following inhibitors and enzymes: Kunitz inhibitor
      (BPTI) with trypsin, trypsinogen and kallikrein; turkey ovomucoid 3rd domain
      (OMTKY3) with alpha-chymotrypsin and the Streptomyces griseus protease B; the
      potato chymotrypsin inhibitor with the protease B; and the barely chymotrypsin
      inhibitor and eglin-c with subtilisin and thermitase. Using X-ray coordinates of
      the nine complexes, we estimated the contributions that hydrophobic effect,
      electrostatic interactions and side-chain conformational entropy make towards the
      stability of the complexes. The calculated delta G values showed good agreement
      with the experimentally measured ones, the only exception being the
      kallikrein/BPTI complex whose X-ray structure was solved at an exceptionally low
      pH. In complexes with different enzymes, the same inhibitor residues contributed
      identically towards complex formation (delta G(residue) Spearman rank correlation
      coefficient 0.7 to 1.0). The most productive enzyme-contacting residues in
      OMTKY3, eglin-c, and the chymotrypsin inhibitors were found in analogous
      positions on their respective binding loops; thus, our calculations identified a
      functional (energetic) motif that parallels the well-known structural similarity
      of the binding loops. The delta G values calculated for BPTI complexed with
      trypsin (-21.7 kcal) and trypsinogen (-23.4 kcal) were similar and close to the
      experimental delta G value of the trypsin/BPTI complex (-18.1 kcal), lending
      support to the suggestion that the 10(7) difference in the observed stabilities
      (KA) of these two complexes reflects the energetic cost of conformational changes
      induced in trypsinogen during the pre-equilibrium stages of complex formation. In
      almost all of the complexes studied, the stabilization free energy contributed by
      the inhibitors was larger than that donated by the enzymes. In the trypsin-BPTI
      complex, the calculated delta G contribution of the amino group from the BPTI
      residue Lys15 (9.7 kcal) was somewhat higher than that arrived at in experiments
      with semisynthetic inhibitor analogs (7.5 kcal). In OMTKY3, different binding
      loop residues are known to affect differently the binding (delta delta G) to
      alpha-chymotrypsin and protease B; a good qualitative agreement was found between
      the calculated delta G(residue) estimates and the experimental delta delta G data
      (correlation coefficient 0.7). Large variations were observed in local surface
      complementarity and related interfacial volume in the two OMTKY3 complexes (by 20
      to 60% for some side-chains).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8254667
TI  - Structure analysis of cytochrome c3 from Desulfovibrio vulgaris Hildenborough at
      1.9 A resolution.
AB  - The three-dimensional X-ray structure of cytochrome c3 from sulfate-reducing
      bacteria Desulfovibrio vulgaris Hildenborough (DvH) (M(r) 13 kDa, 107 residues, 4
      heme groups) has been determined at 1.9 A resolution, by the method of molecular
      replacement, using the homologous part of the refined structure of cytochrome c3
      from D. vulgaris Miyazaki F (DvMF). Crystals of c3 DvH were obtained with space
      group P61, a = 77.0 A, c = 77.2 A, Z = 12, corresponding to two independent
      molecules in the asymmetric unit. The structure was refined to an R-factor of
      19.6%. The structures of the two molecules are analyzed, compared with each other
      and also with that of c3 DvMF. The main-chain atoms are, for the three
      structures, generally within 1.0 A. The intramolecular heme edge to edge
      distances and interplanar angles indicate two groups of values. Shorter distances
      are associated with near-normal angles, while longer distances with acute angles.
      Moreover, two of the four hemes, II and IV, are close to only one other heme,
      while the remaining two hemes, I and III, have two close neighbors each. The two
      histidine residues that co-ordinate the heme irons on the fifth and sixth
      positions are nearly parallel, except in the case of heme II. The only
      substitution from DvMF which is inside the molecule, A68V, occurs in the vicinity
      of that same heme. However, the non-paralellism between the two flanking
      histidine residues was also observed in DvMF. Heme II has a conserved higher
      exposure to solvent and one of the lowest redox potentials in the fully oxidized
      forms of the two cytochromes. A comparison between data obtained by spectroscopic
      techniques, nuclear magnetic resonance and electron paramagnetic resonance, and
      the structural results presented here, indicates two types of interactions,
      between hemes I and II and between hemes III and IV.

PMID- 8254668
TI  - Evolution of allosteric control in glycogen phosphorylase.
AB  - In relation to the primary sequence and three-dimensional structure of rabbit
      muscle glycogen phosphorylase, we have carried out a comparative sequence
      analysis of phosphorylases from human, rat, Dictyostelium, yeast, potato and
      Escherichia coli. Based on sequence similarity, a large region of the protein is
      shared by these enzymes extending from alpha-helix-1 to the last alpha-helix-33.
      Conserved residues are equally distributed between the N and C-terminal domains
      and occur primarily in buried residues. Phylogenetic analysis indicates that the
      two isozymes within either E. coli, potato or Dictyostelium are more closely
      related to each other than they are to other phosphorylases. Yeast phosphorylase
      is most closely related to the Dictyostelium isozymes. Mammalian muscle and brain
      isozymes are more closely related to each other than to the liver isozyme and the
      muscle isozyme is evolving at the slowest rate. All phosphorylases exhibit high
      conservation of active site and pyridoxal phosphate binding residues. Most
      phosphorylases also exhibit high conservation of sugar binding residues in the
      glycogen storage site. Phosphorylation and AMP binding site residues are poorly
      conserved in non-mammalian phosphorylases. In contrast, glucose-6-P binding
      residues are highly conserved in four of the seven non-mammalian enzymes.
      Analysis of interacting pairs of dimer contact residues indicates that they can
      be grouped into three relatively independent networks. One network contains
      phosphorylation and AMP binding residues and is poorly conserved in non-mammalian
      enzymes. A second network contains glucose-6-P binding residues and is highly
      conserved in enzymes containing a conserved glucose-6-P binding site. A third,
      conserved network contains residues within the tower helix and gate loop. A model
      for the evolution of allostery in phosphorylase is proposed, suggesting that
      glucose-6-P inhibition was an early control mechanism. The later creation of
      primarily distinct ligand binding sites for AMP/phosphorylation control may have
      allowed the establishment of a separate dimer contact network for propagating
      conformational changes leading to activation rather than inhibition of enzyme
      activity.

PMID- 8254669
TI  - Crystallographic refinement of Bowman-Birk type protease inhibitor A-II from
      peanut (Arachis hypogaea) at 2.3 A resolution.
AB  - The crystal structure of Bowman-Birk type protease inhibitor A-II from peanut was
      refined at 2.3 A resolution using a restrained least-squares method. The
      crystallographic R-factor is 0.196 for 7697 reflections with F > 3 sigma (F) in
      the range from 6.0 to 2.3 A resolution. Two molecules in an asymmetric unit are
      independently refined and, their structures are compared with each other. The
      inhibitor molecule has an elongated shape with two reactive sites, one at both
      ends of the longest dimension. As a secondary structure, a 4-stranded beta-sheet
      like structure is found, in which two water molecules bind two 2-stranded beta
      sheets together with six hydrogen bonds. The molecule is constructed by two
      homologous domains which are related by an intramolecular pseudo 2-fold axis. The
      structure and atomic B-factors of peptide loops containing a reactive site were
      compared with that of adzuki bean Bowman-Birk type inhibitor in the complex with
      bovine beta-trypsin. This comparison shows that no significant structural change
      occurs in the reactive site of inhibitor at the formation of the inhibitor
      protease complex, but structural rigidity around the reactive site seems to
      increase.

PMID- 8254670
TI  - Nuclear magnetic resonance solution structure of dendrotoxin K from the venom of
      Dendroaspis polylepis polylepis.
AB  - The solution structure of dendrotoxin K (Toxin K), a protein consisting of one
      polypeptide chain with 57 residues purified from the venom of the black mamba,
      Dendroaspis polylepis polylepis, was determined by nuclear magnetic resonance
      (NMR) spectroscopy. On the basis of virtually complete sequence-specific 1H NMR
      assignments, including individual assignments for 38 pairs of diastereotopic
      substituents and side-chain amide protons, a total of 818 nuclear Overhauser
      effect distance constraints and 123 dihedral angle constraints were identified.
      Using this input, the solution structure of Toxin K was calculated with the
      program DIANA, and refined by restrained energy-minimization with a modified
      version of the program AMBER. The average root-mean-square deviation (r.m.s.d.)
      relative to the mean atomic co-ordinates of the 20 conformers selected to
      represent the solution structure is 0.31 A for all backbone atoms N, C alpha and
      C', and 0.90 A for all heavy-atoms of residues 2 to 56. The solution structure of
      Toxin K is very similar to the solution structure of the basic pancreatic trypsin
      inhibitor (BPTI) and the X-ray crystal structure of the alpha-dendrotoxin from
      Dendroaspis angusticeps (alpha-DTX), with r.m.s.d. values of 1.31 A and 0.92 A,
      respectively, for the backbone atoms of residues 2 to 56. Some local structural
      differences between Toxin K and BPTI are directly related to the fact that
      intermolecular interactions with two of the four internal molecules of hydration
      water in BPTI are replaced by intramolecular hydrogen bonds in Toxin K.

PMID- 8254671
TI  - A structure refinement method based on molecular dynamics in four spatial
      dimensions.
AB  - We have developed a method for structure refinement based on molecular dynamics
      in four spatial dimensions (4D-MD). The method was applied with success to the
      structure refinement of Cyclosporin A (CPA) and the lac-repressor headpiece (LAC)
      using atom-atom distance restraints derived from NMR data, two cases where
      conventional MD refinement methods failed. In the case of CPA we were able to
      refine seven out of nine substantially different structures, while conventional
      MD only refines three structures. Previously, it had appeared to be impossible to
      refine a given LAC structure with conventional MD methods, manual modifications
      were necessary in order to fulfil all the distance restraints. In this study we
      show that LAC can be refined without manual interference and using only 5000
      steps (10 ps) of 4D-MD. The latter result is particularly interesting because it
      indicates that this method may be a very useful tool when modelling loops in
      proteins.

PMID- 8254672
TI  - Refinement and analysis of the structure of the first two domains of human CD4.
AB  - The structure of a fragment of human CD4 containing two immunoglobulin (Ig)-like
      domains has been determined by X-ray crystallography and refined at 2.2 A
      resolution. The structure determination involved iterative building and simulated
      annealing refinement, beginning with a partial model. Comparison of domain 1 with
      an Ig variable domain shows that CD4 has a long and prominent CDR2-like loop (the
      C"C" corner) and shortened CC' and FG loops (which mediate dimerization in IgV
      modules). Comparison of domain 2 with Ig modules and domain 1 shows that it can
      be described as a truncated Ig V domain, in which strands C" and D are deleted.
      The intersheet disulfide in domain 2 is absent, and there is an altered packing
      of the two beta-sheets together with a remodeling of the hydrophobic core. The
      interface between domains 1 and 2 is a lap joint with an extensive hydrophobic
      surface. The key features of domain 1 that contribute to the interface are found
      at corresponding positions in domain 2, leading us to propose that the contact
      between domains 2 and 3 will resemble the one between domains 1 and 2.

PMID- 8254673
TI  - Comparative protein modelling by satisfaction of spatial restraints.
AB  - We describe a comparative protein modelling method designed to find the most
      probable structure for a sequence given its alignment with related structures.
      The three-dimensional (3D) model is obtained by optimally satisfying spatial
      restraints derived from the alignment and expressed as probability density
      functions (pdfs) for the features restrained. For example, the probabilities for
      main-chain conformations of a modelled residue may be restrained by its residue
      type, main-chain conformation of an equivalent residue in a related protein, and
      the local similarity between the two sequences. Several such pdfs are obtained
      from the correlations between structural features in 17 families of homologous
      proteins which have been aligned on the basis of their 3D structures. The pdfs
      restrain C alpha-C alpha distances, main-chain N-O distances, main-chain and side
      chain dihedral angles. A smoothing procedure is used in the derivation of these
      relationships to minimize the problem of a sparse database. The 3D model of a
      protein is obtained by optimization of the molecular pdf such that the model
      violates the input restraints as little as possible. The molecular pdf is derived
      as a combination of pdfs restraining individual spatial features of the whole
      molecule. The optimization procedure is a variable target function method that
      applies the conjugate gradients algorithm to positions of all non-hydrogen atoms.
      The method is automated and is illustrated by the modelling of trypsin from two
      other serine proteinases.

PMID- 8254674
TI  - The crystal structure of a new high-calcium form of annexin V.
AB  - Annexin V was crystallized in the presence of a high concentration of calcium and
      the structure refined at 1.9 A resolution. The crystals are triclinic (P1) with
      three molecules per asymmetric unit and pseudo-R3 symmetry, reflecting a tendency
      of annexin to form trimers. The overall structure of the protein is similar to
      that seen in other crystal forms. There are, however, significant changes in
      domain III, where a new calcium site is formed. The whole region surrounding this
      site is reorganized in our structure, rendering annexin V more symmetrical and
      more alike annexin I. The formation of the new calcium site causes the
      displacement of Trp187 from a buried to an exposed conformation, a change that
      has recently been demonstrated by fluorescence measurements. The affinity of the
      different potential calcium sites is modulated: there is no calcium bound in
      domains II and IV, while up to two secondary calcium ions sites (in domains I and
      III) can substitute, depending on the calcium concentration present. We suggest
      that annexin can act as a calcium buffer, binding or releasing calcium depending
      on its local concentration. Our results also show that annexin displays inherent
      mobility which, together with its capacity to modulate the calcium affinity of
      its sites, can be of importance for its function on the membrane surface.

PMID- 8254675
TI  - Refinement of the F-actin model against X-ray fiber diffraction data by the use
      of a directed mutation algorithm.
AB  - The F-actin model has been refined by a Directed Mutation Algorithm, a
      reiterative procedure which combines a Monte-Carlo method of selecting subdomains
      to be refined at each cycle with a non-linear least-squares routine to get the
      best fit for the particular selected domains. The G-actin crystal structure was
      used as a starting model. The experimental data were obtained by X-ray fiber
      diffraction patterns from oriented F-actin gels. After 250 cycles we were able to
      obtain an almost perfect fit of the calculated diffraction pattern to the
      experimental diffraction pattern as well as a reasonable stereochemistry
      including intermolecular interactions of the actin monomers with an r.m.s. shift
      in the C alpha-positions of 3.2 A from the crystal coordinates. The
      stereochemistry of the intersubunit packing was calculated by molecular dynamics
      using the program X-PLOR. In addition, the binding site of phalloidin, a cyclic
      heptapeptide from the mushroom Amanita phalloides, could be determined.
      Furthermore, we were able to determine differences in the structures of F-actin
      with and without phalloidin. The method proved itself robust and showed a high
      degree of convergence.

PMID- 8254676
TI  - Projection structure of halorhodopsin from Halobacterium halobium at 6 A
      resolution obtained by electron cryo-microscopy.
AB  - Two-dimensional crystals of halorhodopsin (HR), in space group p42(1)2 (a = 102
      A) have been obtained using the overexpressing Halobacterium halobium strain D2.
      An HR membrane fraction with the same buoyant density as purple membrane (HR-PM)
      was obtained by homogenization and sucrose gradient purification and used for
      electron cryomicroscopic analysis. Electron micrographs and electron diffraction
      patterns of HR-PM were recorded at liquid nitrogen temperatures. The micrographs
      showed significant diffraction out to 9 A resolution optically and to 6 A after
      computer processing. By combining data from electron micrographs and electron
      diffraction patterns, a projection map of HR was calculated. The crystal form of
      the isolated HR consists of one membrane in which alternating halorhodopsin
      tetramers are oriented in opposite directions across the membrane. It is not
      known whether this occurs by misinsertion of some of the molecules in vivo, or by
      adventitious fusion at some point during isolation. The projected structure of
      the HR molecule to a resolution of 6A is almost identical to that found for
      bacteriorhodopsin (BR). This physical structural similarity thus complements the
      known sequence relatedness to BR.

PMID- 8254677
TI  - Crystal structural analysis of mutations in the hydrophobic cores of barnase.
AB  - We have solved and analysed the crystal structures of five mutants in the
      hydrophobic core of barnase to investigate the structural basis for the
      contribution of hydrophobic residues and side-chain packing to the stability of
      globular proteins. In case ease, an amino acid side-chain has been replaced with
      one of smaller volume. The overall structures of four Ile-->Val mutants (residues
      51, 76, 88 and 96) and one Leu-->Val mutant (residue 89) are all isomorphous with
      the wild-type structure. The magnitude and nature of structural shifts in the
      three hydrophobic core regions of barnase depend on the local environment of the
      substitution site, but have some features in common. (1) Side-chain atoms move to
      a greater extent than do main-chain atoms. (2) Repacking at the substitution site
      is achieved by either a rigid body shift of side-chain atoms (for Ile-->Val76 and
      Ile-->Val96 mutants), or by a combination of a side-chain shift and rotation (for
      Ile-->Val51 and Ile-->Val88 mutants). The mutated residue moves to the greatest
      extent, and generally in the direction of the created cavity (the largest atomic
      shift is 0.9 A, for Ile-->Val51). The space left behind from such shifts is not
      seen to be filled by neighbouring side-chains. (3) Where a cavity remains after
      mutation, it does not contain any solvent molecules. (4) There is no correlation
      between the extent of structural movements and the atomic temperature factors of
      atoms that have moved. (5) Structural movements are not large enough to disrupt
      hydrogen bonding. Valine 88, in the Ile-->Val88 mutant, is disordered and the
      electron density suggests several side-chain conformations. The reduction in the
      volumes of the cavities introduced upon mutation, due to collapse of the
      surrounding structure, ranges from 11% (Ile-->Val96) to 90% (Ile-->Val51).

PMID- 8254678
TI  - Crystallization and X-ray diffraction study of recombinant platelet-derived
      endothelial cell growth factor.
AB  - Crystals of recombinant platelet-derived endothelial cell growth factor (PD-ECGF)
      were obtained by the hanging drop vapour diffusion technique. The crystals belong
      to the space group P2(1)2(1)2(1) with unit cell dimensions a = 63.7 A, b = 70.4
      A, c = 219.6, alpha = beta = gamma = 90 degrees, and probably contain a single
      dimer in the asymmetric unit. Diffraction to a minimum Bragg spacing of 3.5 A has
      been obtained using a synchrotron X-ray source.

PMID- 8254679
TI  - Preliminary X-ray crystallographic study of the proteasome from Thermoplasma
      acidophilum.
AB  - Single cystals of proteasomes from the archaebacterium Thermoplasma acidophilum
      were obtained using the hanging-drop vapor diffusion method. The crystals
      diffract to better than 3.0 A and belong to the orthorhombic space group
      P2(1)2(1)2(1) with unit cell dimensions a = 308.9 A, b = 208.8 A and c = 116.9 A.
      There is one molecular complex in the asymmetric unit. Two potentially useful
      heavy-atom derivatives have been obtained. The self-rotation function of the
      native Patterson map shows local sevenfold symmetry, consistent with the low
      resolution structure obtained by electron microscopic techniques. The unit cell
      dimensions and crystal symmetry together with the shape and size of the
      proteasome suggest a packing arrangement of proteasome molecules in the unit
      cell, with their cylinder axis nearly parallel to the crystallographic a-axis.

PMID- 8254680
TI  - Crystallization and preliminary X-ray analysis of papaya mosaic virus coat
      protein.
AB  - Papaya mosaic virus coat protein has been treated with trypsin and a large
      fragment of the intact protein has been crystallized in space group P3(1)21 or
      P3(2)21 (unit cell dimensions: a = b = 110 A, c = 237 A). The crystals diffract
      to 3.5 A resolution. Crystals of the untreated protein have also been grown. The
      untreated protein crystals diffract to 4 A resolution, but have a large mosaic
      spread. They have the same space group as the trypsin-treated protein crystals,
      but a much smaller unit cell (a = b = 72 A, c = 240 A).

PMID- 8254681
TI  - Crystallization and preliminary X-ray analysis of (1,3)- and (1,3;1,4)-beta-D
      glucanases from germinating barley.
AB  - (1,3)-beta-D-Glucanase isoenzyme GII and (1,3;1,4)-beta-D-glucanase isoenzyme EII
      from barley have been crystallized by the hanging drop method in the presence of
      ammonium sulphate. The crystals of the (1,3)-beta-D-glucanase, which diffract to
      about 1.8 A resolution, belong to the trigonal space group P3(1)2(1)2 (or
      P3(2)2(1)2) with cell constants a = b = 86.9 A, c = 156.0 A and contain two
      molecules in the asymmetric unit. The crystals of the (1,3;1,4)-beta-D-glucanase
      which diffract to better than 1.8 A resolution, belong to the tetragonal space
      group P4(3)2(1)2 (or P4(1)2(1)2) with cell constants a = b = 87.4 A, c = 109.5 A
      and contain one molecule in the asymmetric unit.

PMID- 8254682
TI  - Hepatitis A virus 3C proteinase: some properties, crystallization and preliminary
      crystallographic characterization.
AB  - Several isoforms of the wild-type and three mutant hepatitis A virus (HAV) 3C
      proteinases have been isolated and characterized. The active site cysteine
      residue (residue 172) was found to be responsible for the formation of some of
      these isoforms. The double mutant C24S/C172A of the HAV 3C proteinase, in which
      both cysteine residues have been replaced by site-directed mutagenesis, was
      crystallized. The crystals belong to the hexagonal space group P6(1)22 (or its
      enantiomorph, P6(5)22) with unit cell dimensions a = b = 65.2 A, c = 246.1 A and
      diffract X-rays to 2.3 A resolution.

PMID- 8254683
TI  - Preliminary crystallographic study of a complex between an Fab of a monoclonal
      feline peritonitis virus neutralizing antibody and its anti-idiotypic Fab.
AB  - A complex between an Fab fragment of an E2 specific feline infectious peritonitis
      virus neutralizing antibody 730.1.4 and Fab fragment from anti-idiotypic
      monoclonal antibody 409.5.3, was crystallized from ammonium sulfate using vapor
      diffusion methods. The complex crystals diffract to about 2.9 A resolution and
      are of orthorhombic space group P2(1)22(1) with a = 75.2 A, b = 80.6 A and c =
      187.6 A. There are two Fab molecules, or one idiotype-anti-idiotype complex,
      comprising the asymmetric unit. The long 187.6 A c axis suggests that the long
      axis of the complex might lie along this direction. Although small and radiation
      sensitive, crystals are suitable for three-dimensional structural analysis.

PMID- 8254684
TI  - Crystallization of single-chain Fv proteins.
AB  - Single-chain Fv (sFv) proteins consist of the variable heavy chain (VH) and
      variable light chain (VL) domains of an antibody, covalently joined by an
      engineered polypeptide linker. We report the crystallization of single-chain Fv's
      with specificities for fluorescein (4-4-20 sFv) and the TAG-72 pan-carcinoma
      glycoprotein antigen (CC49 sFv). Concentration of these proteins, preliminary to
      crystallization, results in a monomer-multimer equilibrium, causing aggregation
      which interferes with crystallization. Aggregation has been observed to depend
      primarily on an intact linker between VL and VH domains, although other factors
      are likely to modulate this phenomenon as well, including the specific identity
      of Fv and ligand, presence or absence of the ligand, linker length and possibly
      sequence. We have found two methods to overcome sFv aggregation, both of which
      yield X-ray diffraction quality crystals. The first, discovered serendipitously,
      is by introducing a proteolytic clip into the linker region (effectively yielding
      an Fv fragment). The second is the purification of the sFv dimer form, with
      linker regions intact, from an equilibrium mixture of aggregates. The sFv
      molecular association in a dimer is believed to be unusual in that each VL/VH
      interface may not be formed by the two linker-connected VL and VH domains, but
      rather by interaction of VL and VH domains from two distinct sFv monomers.
      Structure determination of the CC49 sFv dimer, with the 14-residue linker
      designated 212, is underway to test this model. Increasing linker length, to
      relieve steric strain on the monomer, and inclusion of the appropriate antigen,
      to slow transitions between monomeric and multimeric forms, may prove valuable
      strategies with sFv proteins less amenable to crystallization.

PMID- 8254685
TI  - Preliminary X-ray diffraction studies of ribgrass mosaic virus.
AB  - Fiber diffraction data were collected from oriented sols of ribgrass mosaic virus
      and a lead derivative of the virus. Two lead binding sites were found. Two
      intersubunit carboxylcarboxylate pairs, different from those in other
      tobamoviruses, are predicted to control viral assembly and disassembly. One of
      the carboxyl-carboxylate pairs forms part of a lead binding site.

PMID- 8254686
TI  - Crystallization and preliminary X-ray studies on the core proteins of
      cellobiohydrolase I and endoglucanase I from Trichoderma reesei.
AB  - The catalytic core domains of cellobiohydrolase I (CBHI) and endoglucanase I
      (EGI) from Trichoderma reesei have been crystallized using the hanging drop
      vapour diffusion method. In the case of CBHI, use of polyethylene glycol 20,000,
      and calcium chloride at low pH produced good quality single crystals suitable for
      X-ray studies. The crystals belong to a primitive orthorhombic space group with
      unit cell dimensions a = 84.0 A, b = 86.2 A, c = 111.8 A, and diffract beyond 2.0
      A resolution. Bipyramidal crystals of EGI core were grown from ammonium sulphate
      at pH 7.5. The crystals are tetragonal, either P4(1)22 or the enantiomorph
      P4(3)22, with cell dimensions a = b = 101.8 A and c = 198.0 A, and at best
      diffract to a resolution of 2.5 A.

PMID- 8254687
TI  - Preliminary crystallographic studies of crotin II.
AB  - Crotin II isolated from the seeds of Euphorbiacea Croton tiglium has been
      crystallized. Crystals were grown by vapor diffusion using KCl as the
      precipitant. The crystal of crotin II belongs to the space group P6(1) or P6(5)
      with cell parameters a = b = 94.62 A, c = 28.43 A, alpha = beta = 90 degrees,
      gamma = 120 degrees. The asymmetric unit contains one molecule of 15,000 Da. A
      data set to 1.82 A has been collected on an area detector.

PMID- 8254688
TI  - Crystallization and preliminary X-ray analysis of the uracil-DNA glycosylase DNA
      repair enzyme from herpes simplex virus type 1.
AB  - A 28.5 kDa catalytic fragment of the uracil-DNA glycosylase DNA repair enzyme
      from Herpes simplex virus type 1 (HSV-1) has been crystallized using protein from
      a highly expressing Escherichia coli clone of the Herpes simplex virus type 1 UL2
      gene. The protein crystallizes at 12 mg/ml from 11% (w/v) polyethylene glycol
      8000 at pH values in the range 6.8 to 7.0, in the presence of (NH4)2SO4. Long
      trigonal rods (0.08 mm x 0.08 mm x > 0.5 mm) diffract beyond 3.0 A using a
      laboratory source. The enzyme crystallizes in P3(1) (or P3(2)) a = 65.3 A, c =
      49.0 A with a single molecule in the asymmetric unit and an estimated solvent
      content of 41% by volume.

PMID- 8254689
TI  - Human immunodeficiency virus (HIV) infection epidemic: medical and social issues
      and the unresolved dilemmas.

PMID- 8254690
TI  - Why the NMA: its heritage revisited and future challenges assessed. Inaugural
      address.

PMID- 8254691
TI  - Chest pain admissions: characteristics of black, Latino, and white patients in
      low- and mid-socioeconomic strata.
AB  - To assess the potential impact of socioeconomic status (SES) factors on health
      care seeking behavior for suspected acute coronary artery disease symptoms, equal
      numbers of black, Latino, and white patients seeking care for chest pain at two
      large hospital emergency rooms were studied. Differences between low and middle
      SES groups with respect to pre-attack health, health history, ethnicity, gender,
      and modes of transportation to the hospital were explored. Highly significant
      self-reported differences between low SES and middle SES patients were found as
      follows: low SES subjects were more likely to describe themselves as being in
      fair to poor general health (68% versus 18%), had more frequent chest pain,
      reported other types of heart disease, were more often current smokers, more
      likely to be black or Latino, and to be younger. Members of the low SES group
      also were less [corrected] likely to have known cholesterol levels, to have used
      estrogen, to have had a prior ECG or cardiac surgery, to be nonsmokers, to have
      had a stress test, and to have typical angina. Middle SES subjects more often
      described typical angina, prior use of estrogen (females), congenital, rheumatic,
      or family history of heart disease, prior knowledge of high cholesterol, were
      more likely to be of the male gender, and to be older than the low SES cohort.
      The data reveal that low SES subjects, with markedly less health-care resources
      compared with middle SES subjects, have a worse general health and cardiac risk
      profile despite the fact that they were significantly younger (mean age 53.4
      versus 60.7, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254692
TI  - Psychological characteristics related to cocaine use during pregnancy: a
      postpartum assessment.
AB  - This study assessed four psychological factors that have been suggested by
      previous research to be highly correlated with drug use. Twenty-one postpartum
      urban African-American women served as the research participants. At parturition,
      10 infants tested positive for cocaine and 11 did not. Measures of depression
      (Beck Depression Index), anxiety (Spielberger Trait Anxiety Inventory),
      anger/self-control (Self-Analysis Questionnaire), and sociopathy (California
      Personality Inventory subscale) were obtained from the mothers within 6 weeks of
      delivery. Women who gave birth to cocaine-positive infants were significantly
      more depressed and had significantly higher sociopathy scores than their cocaine
      negative counterparts. No differences with respect to anxiety and anger were
      obtained. The implications of these findings, as well as the potential adverse
      effects of cocaine use during pregnancy, are discussed.

PMID- 8254693
TI  - Primary aldosteronism caused by an adrenal tumor: a correctable cause of
      hypertension.
AB  - Primary aldosteronism due to an adrenal tumor is rare. When found, it can be
      treated surgically and cured. This is a case report of a 41-year-old man with a
      long history of severe hypertension who complained of weakness and weight loss.
      Laboratory studies revealed hypokalemia and marked elevation of the serum
      aldosterone level. A computed tomography scan revealed a left adrenal mass that
      increased in size over 3 months' time. A left adrenalectomy was done, and the
      patient has had a dramatic decrease in his blood pressure and has returned to
      work.

PMID- 8254694
TI  - Challenges in the management of pancreatic and duodenal injuries.
AB  - A retrospective analysis of 44 consecutive patients with pancreatic or duodenal
      injuries admitted to an urban trauma center over a 6-year period was undertaken.
      Thirty-three patients had pancreatic injuries, including eight with combined
      duodenal injuries. Eleven patients had duodenal injuries. The mean age was 28
      years, and 93% of the patients were male. Penetrating abdominal trauma accounted
      for the majority of injuries. Class I pancreatic injuries were the most common
      (55%), followed by those with class III (21%) and class II (18%). The majority
      (55%) of pancreatic injuries were managed by drainage with or without suturing;
      distal pancreatectomy was used in 39% of patients. Duodenal injuries were managed
      by primary repair in 50% of cases and pyloric exclusion/diverticulization
      techniques were used in 20% of cases. The mean first 24 hours transfusion
      requirement was 6.8 packed red blood cells. Complications were common, occurring
      in 61% of patients surviving longer than 24 hours. Intraabdominal abscess
      developed in 31% of all patients, 42% of whom required relaparotomy. Pancreatic
      fistulas occurred in 16% of patients with pancreatic injuries. Six patients died,
      83% within 8 hours of admission, all as a result of gunshot wounds. Increased
      mortality was seen in patients with higher blood transfusion requirements, higher
      penetrating abdominal trauma index, shotgun wounds, the need for
      pancreaticoduodenectomy, hypotension on admission, and the presence of an
      associated major vascular injury. We conclude that early operation and
      efficacious control of hemorrhage is of prime importance in decreasing the
      mortality rate associated with these injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254695
TI  - The many faces of atypical sinusitis.
AB  - The physician must be alert to the possibility of unsuspected sinusitis when
      evaluating a patient with chronic cough, sore throat, fever of unknown origin,
      supraglottitis, pneumonia, or headache. This article presents four cases in which
      atypical or asymptomatic sinusitis was discovered that could have caused
      significant or potentially life-threatening complications. In each case, the
      sinusitis was initially unsuspected. A complete nasal evaluation is warranted
      following decongestion of the nasal cavity when conditions are present. A
      screening sinus computed tomography scan may be indicated when sinusitis is
      strongly suspected even in the absence of typical clinical symptoms. Exact
      identification of the organism causing the infection may require sinus aspirate
      or tissue culture.

PMID- 8254696
TI  - Black medical pioneers: African-American 'firsts' in academic and organized
      medicine. Part three.

PMID- 8254697
TI  - In vitro cyanide release of four prussian blue salts used for the treatment of
      cesium contaminated persons.
AB  - Prussian blue salts are used in clinical practice as an antidote for the
      treatment of humans contaminated with radioactive cesium. A decomposition product
      of these Prussian blue salts may be the highly toxic cyanide. A method to
      simulate gastrointestinal cyanide-release was applied to four different Prussian
      blue salts: K3Fe[Fe(CN)6], Fe4[Fe(CN)6]3, NH4Fe[Fe(CN)6] (pur. and unpur.).
      Cyanide-release was higher in artificial gastric juice than in water and
      artificial intestinal juice. Under all conditions cyanide-release from
      Fe4[Fe(CN)6]3 was the lowest. Since Fe4[Fe(CN)6]3 also binds more cesium, it
      appears to be the most suitable Prussian blue salt for use as an antidote after
      radiocesium contamination in humans.

PMID- 8254698
TI  - In vivo binding of radiocesium by two forms of Prussian blue and by ammonium iron
      hexacyanoferrate (II).
AB  - The effect of two forms of Prussian blue, soluble K3 Fe[Fe(CN)6] and insoluble
      Fe4[Fe(CN)6]3, and of ammonium iron hexacyanoferrate (II) (NH4Fe[Fe(CN)6] on
      intestinal radiocesium absorption was investigated in rats, pigs, and humans. In
      rats 5 mg of antidote administered 2 min before 134Cs tracer reduced radiocesium
      absorption to 2.4-6.3% of the oral dose. In pigs fed with Chernobyl-contaminated
      whey under normal feeding conditions for a 27 day period, radiocesium activity
      concentration was reduced from 360 Bq/kg in control animals to 10-30 Bq/kg by 5 g
      antidote/d. In man 1 g of oral Prussian blue diminished the cesium absorption
      from a 134Cs-labelled test meal to 5.6-6.4% of the controls. The inhibitory
      effects of colloidally soluble K3 Fe[Fe(CN)6] and of (NH4Fe[Fe(CN)6] were similar
      with slightly less inhibition by the insoluble Fe4[Fe(CN)6]3.

PMID- 8254699
TI  - The basis of the paradoxical disturbance of temperature perception in ciguatera
      poisoning.
AB  - The basis of the paradoxical reversal of temperature perception commonly
      described in ciguatera poisoning has never been defined. The sensations
      experienced are described as tingling, burning, "dry ice-like", smarting, and
      "electric". Studies have demonstrated that these types of sensations are
      generated in C-polymodal nociceptor fibers in skin and deep structures and the
      intensity of these sensations depends on the intensity of discharge in these
      fibers. Ciguatoxin causes persistent sodium channel opening in nerve membrane
      resulting in oscillations in membrane potentials and runs of spontaneous
      discharges. Studies on ciguatera victims in which their hands were immersed in
      water baths ranging from 0 degree C to 50 degrees C, suggest the paradoxical
      sensory discomfort experienced is, most likely, a result of an exaggerated and
      intense nerve depolarization occurring in peripheral small A-delta myelinated and
      in particular, C-polymodal nociceptor fibers. Gross temperature perception was
      found to be intact in ciguatera poisoning and reversal of temperature does not
      occur.

PMID- 8254700
TI  - Clinical observations and medical outcome in 149 cases of arsenate ant killer
      ingestion.
AB  - One hundred forty-nine (149) consecutive cases of arsenate-containing ant killer
      reported to the Minnesota Regional Poison Center over 4 1/2 months were
      retrospectively reviewed with a follow-up (1 week to 3 months) completed in 132
      (89%) of the population studied. One hundred and forty eight (99%) of the
      ingestions were accidental. The majority of cases involved children 3 years of
      age and younger. Only three patients accidentally ingesting the product were
      symptomatic (mild episodes of vomiting and diarrhea which cleared in all patients
      within 12 hours). No patient was referred to a medical center for treatment and
      no patient reached on follow-up reported any additional ill effects as a result
      of the exposure. In addition to the 149 patients in this series, we describe two
      representative patients who accidentally ingested similar amounts of sodium
      arsenate-containing ant killer, resulting in urine arsenic of 3500 micrograms/24
      h and 5819 micrograms/24 h. They required no chelation treatment and had no
      evident sequelae during 4-6 months of medical follow-up. This experience supports
      poison center directed home management for the majority of single, acute, and
      accidental ingestions of small quantities (< 5 mL) of arsenate-containing ant
      killers as a safe alternative to medical center referral and adverse reactions to
      chelation.

PMID- 8254701
TI  - Acute poisoning in Izmir, Turkey--a pilot epidemiologic study.
AB  - Epidemiologic data on poisonings in Turkey are extremely limited. This is a
      retrospective chart review to describe the prevalence of poisoning in both adults
      and children, the presenting clinical features, morbidity and mortality to
      identify how poisoning in Izmir follows the pattern of other countries and how it
      is unique. Three hundred sixty-five poisoned patients presented to the Dokuz
      Eylul University Hospital, Ismir in 1989 to 1990. The distribution frequency of
      substances ingested reflects that of substances available in the home. Poisoning
      episodes in small children were most likely to involve hydrocarbons, analgesic,
      caustics or pesticides (55%). Ethanol, anticonvulsants, tricyclic
      antidepressants, and pesticides (55%). Ethanol, anticonvulsants, tricyclic
      antidepressants, and pesticides were the most common toxins seen in adults. A
      significant number of patients presented late in the course of their poisoning.
      Of those ingesting pharmaceuticals, mushrooms or plants, emesis, but no other
      modes of decontamination, was reported for 21%. Toxin "antidotes",
      gastrointestinal decontamination and enhanced drug removal techniques used in
      other parts of the world were rarely utilized. Nonetheless, only three patients
      (0.8%) died. This pilot study supports the need for a Regional Poison Information
      Center offering poison management advice to the general public as well as to
      members of the health care professions, the initiation of a public education
      campaign, and regional treatment by physicians trained in medical toxicology.

PMID- 8254702
TI  - Fluoxetine: adverse effects and drug-drug interactions.
AB  - This overview summarizes the major and minor side effects and drug interactions
      of fluoxetine. The adverse reactions include the "serotonin syndrome",
      cardiovascular complications, extrapyramidal side effects such as akathisia,
      dyskinesias, and parkinsonian-like syndromes and an apparently increased risk of
      suicidality. Fluoxetine-induced mania and hypomania, seizures and sexual
      disorders are evaluated along with minor symptoms of allergic reactions,
      stuttering, hematological changes, psoriasis, and inappropriate secretion of the
      antidiuretic hormone. The major fluoxetine-drug interactions involve the amino
      acids L-dopa and L-tryptophan, anorexiants, anticonvulsants, antidepressants,
      anxiolytics, calcium channel blockers, cyproheptadine, lithium salts, and drugs
      of abuse. The underlying mechanism and the paradoxical effects of fluoxetine are
      addressed.

PMID- 8254703
TI  - Poisoning caused by the combined ingestion of nifedipine and metoprolol.
AB  - Poisonings due to ingestion of a calcium channel or beta-adrenergic blocker have
      been the subject of several previous reports, but reports of poisoning due to
      combined ingestion of these drugs are infrequent. This is a report of suicidal
      ingestion of nifedipine 600 mg, metoprolol 200 mg, and etizolam 20 mg.
      Intravenous dopamine, norepinephrine, and calcium chloride had little effect but
      the administration of methylprednisolone and glucagon were associated with an
      increase in systolic blood pressure above 100 mm Hg.

PMID- 8254704
TI  - Theophylline toxicity in a premature neonate--elimination kinetics of exchange
      transfusion.
AB  - Exchange transfusion was utilized in the treatment of a 1871 gram female, 32
      weeks gestational age, who received an IV bolus of aminophylline at 11 h for the
      treatment of apnea, with subsequent tachycardia and hypotension. At 22 h, plasma
      theophylline was 369.29 mumol/L (67 mg/L). During a single volume exchange
      transfusion at 33 h, the plasma theophylline decreased 19% and the estimated
      removal of theophylline was 13.5% of the whole body theophylline. The
      theophylline apparent half-times before, during, and after the exchange were
      52.5, 6.6, and 53.3 h respectively.

PMID- 8254705
TI  - Continuous arteriovenous hemoperfusion in meprobamate poisoning.
AB  - A patient with severe meprobamate poisoning presented within 4 h after suicidal
      ingestion of an unknown amount of the drug. The patient was unconscious,
      unresponsive, and hypotensive. Continuous arteriovenous hemoperfusion with coated
      activated charcoal resulted in a clearance of 198.8 +/- 15.6 mL/min with an
      extraction ratio of 0.66 +/- 0.05 (n = 3). There was almost complete elimination
      of the drug from the blood by 16 h. Continuous arteriovenous hemoperfusion, which
      can be performed in areas where dialysis facilities are not available, may be an
      effective adjunct to the treatment of acute meprobamate intoxication,
      particularly in patients with profound hypotension.

PMID- 8254706
TI  - Fatal paraphenylenediamine (hair dye) intoxication in a child resembling Ludwig's
      angina.
AB  - A 6 year-old child with paraphenylenediamine intoxication is presented. The
      patient suffered from sore throat, cough, and anorexia, followed by severe
      dyspnea caused by edema of the tongue, pharynx, and neck, renal failure, and
      metabolic acidosis. A presumptive diagnosis of Ludwig's angina, a severe
      anaerobic infection of the sublingual neck space, was entertained. Despite
      institution of vigorous supportive therapy and administration of antibiotics, the
      child developed irreversible ventricular fibrillation and died eight hours after
      admission. Two days after the patient's death, his father recalled that the child
      and his dog ingested an unidentified substance shortly before the onset of the
      child's symptoms. The dog died within a few hours. The substance was identified
      as the hair dye, paraphenylenediamine.

PMID- 8254707
TI  - Trichlorethylene is radio-opaque.

PMID- 8254708
TI  - The fax machine: a new method of plant identification.

PMID- 8254709
TI  - ELISA for detection of anti-Giardia specific IgM: response in serum.
AB  - Infection with Giardia lamblia (G. duodenalis, G. intestinalis) is common all
      over the world, especially in children. Traditional diagnosis by faecal
      microscopy has only moderate sensitivity; serological tests, although not always
      positive, are acceptable to patients and useful in epidemiological studies. We
      show here that serum IgM separated by column chromatography and assayed by an
      indirect ELISA test can be a useful tool for the diagnosis of giardiasis. One
      hundred and thirty-nine positive sera (based on a single faecal examination), and
      97 negative serum samples from Riyadh, Saudi Arabia, were examined. Taking
      positive results as being 2 s.d. above the mean of the controls, there were 117
      positive results among the microscopically negative controls (3% false
      positives). The sensitivity of the test was 84% and the specificity 97%; the
      predictive value of a positive result is 97.5% and of a negative one 81%.

PMID- 8254710
TI  - Efficacy of chloroquine on Plasmodium falciparum transmitted at Amani, eastern
      Usambara Mountains, north-east Tanzania: an area where malaria has recently
      become endemic.
AB  - In order to assess the response of newly endemic falciparum malaria to currently
      used antimalarials, a field study was conducted in Amani, Tanzania. The efficacy
      of chloroquine (CQ) on Plasmodium falciparum was assessed by in-vivo and in-vitro
      methods. Fifty-four patients with pure falciparum malaria were treated with CQ
      and followed daily for 3 days and weekly for one month. Eighty-three per cent of
      infections exhibited some degree of in-vivo resistance to CQ (46% RI, 28% RII and
      9% RIII). Pretreatment blood samples were obtained from all 54 patients for in
      vitro sensitivity testing for CQ, amodiaquine (AQ), quinine (QN), and mefloquine
      (MQ). In-vitro data correlated well with in-vivo data; 80% of successful isolates
      were resistant to CQ. Forty-five per cent of successful isolates were resistant
      to AQ, 2% to QN, and none to MQ. The antimalarial levels yielding 99% inhibition
      (EC99) for CQ, AQ, QN, and MQ were 12.86, 3.24, 24.09 and 0.81 microM
      respectively. Urine HPTLC revealed CQ metabolites in 15% of study patients who
      denied recent CQ ingestion and had a negative Dill-Glazko test. This implies the
      high rate of CQ resistance observed in this study could be due in part to the
      widespread use of CQ for self-medication. Although the day 3 mean CQ plasma level
      was higher for sensitive and RI infections than for RII and RIII infections, the
      difference did not reach statistical significance. Our study results confirm that
      P. falciparum transmitted at Amani is highly resistant to CQ.

PMID- 8254711
TI  - Tinea capitis in Trinidad.
AB  - Characteristics of clinically diagnosed cases of tinea capitis from Trinidad are
      described. Tinea capitis comprised 29.5% of all dermatophytoses seen at one
      general hospital out-patient dermatology clinic during a one-year period. Males
      were more often affected than females and there was a predominance of patients of
      African descent. Among the dermatophytes cultured Trichophyton tonsurans was the
      most prevalent (52.9%), followed by Microsporum canis (20.0%) and M. audouinii
      (18.6%). Less frequent isolates included M. gypseum (1.9%), T. mentagrophytes var
      granulare (1.4%) and T. rubrum (1.4%).

PMID- 8254712
TI  - Low incidence of hypercalcaemia in tuberculosis in Malaysia.
AB  - In this study we examined the incidence of hypercalcaemia among patients with
      tuberculosis in Malaysia. Serum calcium concentration and other calcium
      metabolism parameters were studied in 43 newly diagnosed tuberculous patients
      from the Kuala Lumpur General Hospital and the National Tuberculosis Centre.
      Forty-four patients admitted to the medical wards of the General Hospital, Kuala
      Lumpur were recruited as controls. The incidence of hypercalcaemia was found to
      be only 1/43 (2.3%). There was no significant difference between the mean serum
      calcium and other calcium metabolism parameters between the patients and the
      controls. Despite earlier reported incidences of 30-50%, this study showed that
      hypercalcaemia in tuberculosis is uncommon in Malaysia.

PMID- 8254713
TI  - A prospective study on some factors which influence the delivery of large babies.
AB  - Data on a total of 492 randomly selected women who delivered at term (37-41
      weeks) singleton babies in the facilities are analysed. These mothers had been
      followed up regularly from the booking clinic till delivery of their babies.
      There were 51 (10.4%) large babies with birth weight > or = 3800 g. Of these, 30
      were males and 21 were females. The mean weight of the males, 4005 +/- 0.188 g,
      was significantly higher than that for females, 3978 +/- 0.197 g. There was a
      significantly increased risk of Caesarean section in the large babies compared
      with the controls with birth weight < 3800 g born in the same period. There was a
      maternal death during the delivery of one of the large babies by Caesarean
      section. The mean total maternal weight gained for birth weight 3800-4000 g was
      14.33 +/- 3.82 kg and for babies weighing over 4000 g was 20.36 +/- 2.6 kg,
      significantly higher than the controls (P < 0.001). Maternal weight gain,
      maternal height, season of delivery and maternal ponderal index at delivery were
      significantly related to the birth of large babies (P < 0.001). Parity was also
      significantly related (P < 0.01). Maternal education and socio-economic class
      were not (P > 0.5). No diabetic mother was included in the analysis.

PMID- 8254714
TI  - Dracunculiasis in Burkina Faso: results of a national survey.
AB  - National surveys using active reporting are essential steps in the global
      dracunculiasis eradication programme. All the known villages of Burkina Faso were
      visited at the end of 1990 by teams of field-workers who organized meetings with
      local informants in order to enquire about all cases of the emergence of Guinea
      worms during the past twelve months. The annual incidence for 1990 was then
      calculated using recent demographic data. Data collected were validated by a
      second survey of a random sample of 221 villages. The national coverage rate was
      99.3% of villages; 42,227 cases were reported. The annual incidence for 1990 was
      46.4 cases per 10,000. There was a pronounced heterogeneity in the spatial
      distribution of endemic foci, with a concentration of cases in the north and
      centre of the country. In Burkina Faso, dracunculiasis has a heterogeneous
      distribution with a pronounced concentration of cases in the North and Centre
      that reach mesoendemic incidence rates.

PMID- 8254715
TI  - Cystic hydatid disease: pitfalls in diagnosis in the Middle East endemic area.
AB  - Ultrasound (US) and computerized tomography (CT) have made a significant
      contribution to accurately localizing focal lesions. Such imaging techniques have
      been found useful in assessing a hydatid aetiology of cystic lesions. However, we
      present 23 cases which demonstrate that these modalities in isolation are not
      adequate in diagnosing hydatid cysts, as claimed from this geographic area.
      Simple, congenital, choledochal and pancreatic pseudocysts were cystic lesions
      misinterpreted as hydatid cysts, as were infective disorders such as amoebiasis
      and tuberculosis. The appearance of a lipoma and an ovarian intra-abdominal
      cystadenoma and an intra-hepatic haematoma were among other conditions that were
      labelled as hydatid cysts on US/CT. However, in all the cyst/mass lesions that
      were misdiagnosed, counter-immunoelectrophoresis (CIEP), with an antigen that
      elicits an arc-5 in immunoelectrophoresis on cellulose acetate membranes as a
      substrate, did not detect any anti-Echinococcus antibodies in patients' sera.
      This was in contrast to the classic indirect haemagglutination test which was
      equivocal in some cases. The CIEP was specific and excluded hydatidosis though
      such a diagnosis was ventured on US and/or CT. We therefore conclude that a
      specific and sensitive serological test is mandatory for confirming a
      preoperative diagnosis of CHD. When surgery is not immediate, a negative
      serological test such as the CIEP would in addition indicate US or CT-guided
      aspiration of cyst fluid for cytological evaluation and/or enzyme immunoassay,
      thereby avoiding the cost and morbidity of laparotomy. Furthermore, chemotherapy
      is now a viable alternative provided the diagnosis is unequivocal. This may be a
      prudent protocol before a further decision on management is envisaged.

PMID- 8254716
TI  - Analysis of medical needs during disasters caused by tropical cyclones:
      anticipated injury patterns.
AB  - This paper is a summary of the data for describing the distribution of injuries
      among people affected by tropical cyclones that have occurred during the past 20
      years. The most striking feature of the data gathered from a review of the
      epidemiologic literature on tropical cyclones is its lack of uniformity. The
      absence of an international classification and coding scheme for recording
      injuries sustained in cyclones also makes planning medical assistance difficult
      following future cyclones and hurricanes. We propose here a simple injury
      classification scheme comprising three components for categorizing injury data.
      Such a standardized disaster injury classification scheme, coupled with other
      types of information about injuries, will greatly aid relief officials in
      efficiently matching available resources to needs, in effectively managing health
      relief operations, and in developing strategies to prevent future cyclone-related
      morbidity and mortality.

PMID- 8254717
TI  - Cell immunofluorescence and brain extract based dot-immunobinding assay in
      identification of arboviruses.
AB  - Infected mouse brain homogenates were semi-purified and used in a dot
      immunobinding assay to identify the corresponding arboviruses.

PMID- 8254718
TI  - Virus receptors: binding, adhesion strengthening, and changes in viral structure.

PMID- 8254719
TI  - Activation of the human immunodeficiency virus type 1 long terminal repeat by
      transforming mutants of human p53.
AB  - We have studied the effects of human wild-type and mutant p53s on the long
      terminal repeat (LTR) promoter of human immunodeficiency virus type 1 (HIV). HeLa
      cells were cotransfected with a wild-type or mutant p53 expression plasmid and a
      plasmid containing a chloramphenicol acetyltransferase reporter gene under HIV
      LTR promoter control. As expected, expression of wild-type p53 inhibited promoter
      function. Expression of a p53 mutated at any one of the four amino acid positions
      175, 248, 273, and 281 correlated with a significant increase of the HIV promoter
      activity. The HIV LTR was also significantly activated in Saos-2 cells that do
      not express endogenous p53. This finding suggests a gain-of-transactivation
      function by mutation of the p53 gene. Cotransfection of wild-type and mutant p53
      281G expression plasmids indicated that either the wild type or the mutant was
      dominant in inhibiting or enhancing promoter activity, respectively, when
      transfected in excess of the other. Transfection experiments showed
      transactivation even when the Sp1, NF-kappa B, and TATA sites in the LTR were
      individually mutated. Synthetic minimal promoter constructs containing two Sp1
      sites or two NF-kappa B sites or an ATF site are also significantly activated by
      the mutant p53-281G. Thus, the mutant protein may activate transcription through
      interaction with either a general transcription factor or a common factor that
      bridges the basal transcription machinery and the transcription factors Sp1, NF
      kappa B, and ATF.

PMID- 8254720
TI  - Phenotypic characterization of insertion mutants of the human immunodeficiency
      virus type 1 Gag precursor expressed in recombinant baculovirus-infected cells.
AB  - A panel of 28 insertion mutants of the human immunodeficiency virus type 1 (HIV
      1) Gag precursor (Pr55Gag) was constructed by linker-insertion mutagenesis and
      expressed in recombinant baculovirus-infected insect cells. One set of 14 mutants
      carried the normal N-myristylation signal; the other set constituted their non-N
      myristylated counterparts. The mutants were characterized with respect to (i)
      assembly and extracellular release of membrane-enveloped budding Gag particles,
      (ii) intracellular assembly and nuclear transport of Gag cores, (iii) specific
      processing of Pr55Gag by HIV-1 protease in vivo, and (iv) binding of Pr55Gag to
      an HIV-1 genomic RNA probe in Northwestern blotting. Insertions within the region
      between amino acid residues 209 and 334 in the CA domain appeared to be the most
      detrimental to Gag particle assembly and release of Gag into the external medium,
      whereas a narrower window, between residues 209 and 241, was found to be critical
      for secretion of soluble Pr55Gag. Differences in Pr55Gag processing in vivo and
      RNA binding in vitro between N-myristylated and non-N-myristylated Gag mutants
      suggested a major conformational role for the myristylated N terminus of Gag
      precursor. In coinfection experiments using wild-type Gag- and mutant Gag
      expressing recombinants, a transdominant negative effect on Gag particle assembly
      and release was observed for insertions located in two separate domains, the
      matrix and nucleocapsid.

PMID- 8254721
TI  - Molecular model of the A subunit of protein phosphatase 2A: interaction with
      other subunits and tumor antigens.
AB  - Protein phosphatase 2A consists of three subunits, the catalytic subunit (C) and
      two regulatory subunits (A and B). The A subunit has a rod-like shape and
      consists of 15 nonidentical repeats. It binds the catalytic subunit through
      repeats 11 to 15 at the C terminus and the tumor antigens encoded by small DNA
      tumor viruses through overlapping but distinct regions at N-terminal repeats 2 to
      8. A model of the A subunit was developed on the basis of the fact that uncharged
      or hydrophobic amino acids are conserved at eight defined positions within each
      repeat. Helical wheel projections suggested that each repeat can be arranged as
      two interacting amphipathic helixes connected by a short loop. Mutational
      analysis of the A subunit revealed that the proposed loops are important for
      binding of tumor antigens, the B subunit, and the C subunit. Native gel analysis
      of mutant A subunits synthesized in vitro demonstrated that the binding region
      for the B subunit, previously thought to include repeats 2 to 8, covers repeats 1
      to 10 and that the B and C subunits cooperate in binding to the A subunit.

PMID- 8254722
TI  - Assembly of vaccinia virus: the second wrapping cisterna is derived from the
      trans Golgi network.
AB  - During the assembly of vaccinia virus, the intracellular mature virus becomes
      enwrapped by a cellular cisterna to form the intracellular enveloped virus (IEV),
      the precursor of the extracellular enveloped virus (EEV). In this study, we have
      characterized the origin of this wrapping cisterna by electron microscopic
      immunocytochemistry using lectins, antibodies against endocytic organelles, and
      recombinant vaccinia viruses expressing proteins which behave as Golgi resident
      proteins. No labelling for endocytic marker proteins could be detected on the
      wrapping membrane. However, the wrapping membrane labelled significantly for a
      trans Golgi network (TGN) marker protein. The recycling pathway from endosomes to
      the TGN appears to be greatly increased following vaccinia virus infection, since
      significant amounts of endocytic fluid-phase tracers were found in the lumen of
      the TGN, Golgi complex, and the wrapping cisternae. Using immunoelectron
      microscopy, we localized the vaccinia virus membrane proteins VV-p37, VV-p42, VV
      p21, and VV-hemagglutinin (VV-HA) in large amounts in the wrapping cisternae, in
      the outer membranes of the IEV, and in the outermost membrane of the EEV. The
      bulk of the cellular VV-p37, VV-p21, and VV-p42 were in the TGN, whereas VV-HA
      was also found in large amounts on the plasma membrane and in endosomes.
      Collectively, these data argue that the TGN becomes enriched in vaccinia virus
      membrane proteins that facilitate the wrapping event responsible for the
      formation of the IEV.

PMID- 8254723
TI  - Nonhomologous RNA recombination in tombusviruses: generation and evolution of
      defective interfering RNAs by stepwise deletions.
AB  - We used a protoplast system to study the mechanisms involved in the generation
      and evolution of defective interfering (DI) RNAs of tomato bushy stunt
      tombusvirus (TBSV). Synthetic transcripts corresponding to different naturally
      occurring TBSV DI RNAs, or to various artificially constructed TBSV defective
      RNAs, were analyzed. The relative levels of competitiveness of different DI RNAs
      were determined by coinoculating their corresponding transcripts into protoplasts
      along with helper genomic RNA transcripts and monitoring the level of DI RNA
      accumulation. Further studies were performed to assess the contribution of naked
      DI RNA stability and DI RNA encapsidation efficiency to the observed levels of
      competitiveness. In addition, the ability of various defective RNAs to evolve to
      alternative forms was tested by serially passaging protoplast infections
      initiated with transcripts corresponding to helper genomic RNA and a single type
      of defective RNA. These studies, and the analysis of the sequences of observed
      recombinants, indicate that (i) replication competence is a major factor
      dictating DI RNA competitiveness and is likely a primary determinant in DI RNA
      evolution, (ii) DI RNAs are capable of evolving to both smaller and larger forms,
      and the rates at which various transitions occur differ, (iii) DI RNA-DI RNA
      recombination and/or rearrangement is responsible for the formation of the
      evolved RNA molecules which were examined, and (iv) sequence complementarities
      between positive- and negative-sense strands in the regions of the junctions
      suggest that, in some cases, base pairing between an incomplete replicase
      associated nascent strand and acceptor template may mediate selection of
      recombination sites. On the basis of our data, we propose a stepwise deletion
      model to describe the temporal order of events leading to the formation of
      tombusvirus DI RNAs.

PMID- 8254724
TI  - Attenuated hepatitis A virus: genetic determinants of adaptation to growth in MRC
      5 cells.
AB  - A live candidate hepatitis A virus vaccine, developed from the HM-175 strain and
      adapted to growth in primary African green monkey kidney (AGMK) cells, was
      adapted to growth in MRC-5 cells. The nucleotide sequence of the MRC-5 cell
      adapted virus was determined and compared with the known sequence of the AGMK
      cell-adapted virus. Thirteen unique mutations, which occurred during passage in
      MRC-5 cells, were identified. Four of the unique mutations were located in a
      cluster in the 5' noncoding region (NC), and three of the remaining nine
      mutations encoded amino acid changes. Infectious chimeric cDNAs were constructed
      from infectious cDNA clones of the AGMK cell-adapted and wild-type HM-175 viruses
      and PCR-amplified cDNA segments of the MRC-5 cell-adapted virus. The viruses
      encoded by these plasmids were recovered after transfection of cultured cells
      with in vitro transcripts, and their growth phenotypes in fetal rhesus kidney 4
      (FRhK-4) and MRC-5 cells were determined. The important growth-enhancing
      mutations could be divided into three sets. Two of these were located in the 5'
      NC region, and the third was located in the 2C nonstructural gene. The mutations
      in the 5' NC region that developed during passage in MRC-5 cells were
      indispensable for efficient growth in MRC-5 cells, but a combination of the two
      groups in the 5' NC region and one in the 2C gene were required to increase
      growth dramatically in MRC-5 cells.

PMID- 8254725
TI  - Evolution of alphaviruses in the eastern equine encephalomyelitis complex.
AB  - Evolution of viruses in the eastern equine encephalomyelitis (EEE) complex was
      studied by analyzing RNA sequences and oligonucleotide fingerprints from isolates
      representing the North and South American antigenic varieties. By using
      homologous sequences of Venezuelan equine encephalomyelitis virus as an outgroup,
      phylogenetic trees revealed three main EEE virus monophyletic groups. A North
      American variety group included all isolates from North America and the
      Caribbean. One South American variety group included isolates from the Amazon
      basin in Brazil and Peru, while the other included strains from Argentina,
      Guyana, Ecuador, Panama, Trinidad, and Venezuela. No evidence of heterologous
      recombination was obtained when three separate regions of the EEE virus genome
      were analyzed independently. Estimates of the overall rate of EEE virus evolution
      (nucleotide substitution) were 1.6 x 10(-4) substitution per nucleotide per year
      for the North American group and 4.3 x 10(-4) for the Argentina-Panama South
      American group. Evolutionary rate estimates for the North American group
      increased over 10-fold (from about 2 x 10(-5) to 4 x 10(-4)) concurrent with
      divergence of two monophyletic groups during the early 1970s. The North and South
      American antigenic varieties diverged roughly 1,000 years ago, while the two main
      South American groups diverged about 450 years ago. Analysis of multiple strains
      isolated from an upstate New York transmission focus during the same years
      suggested that, in certain locations, EEE virus may be relatively isolated for
      short time periods.

PMID- 8254726
TI  - Site-directed mutagenesis of adeno-associated virus type 2 structural protein
      initiation codons: effects on regulation of synthesis and biological activity.
AB  - It has been shown that two of the three adeno-associated virus type 2 capsid
      proteins, B and C, are synthesized from a single spliced transcript. Protein C
      arises from an AUG codon at nucleotide 2810, whereas protein B is initiated by a
      unique eucaryotic initiation codon (ACG) that lies 65 triplets upstream from the
      C origin. The third capsid component, protein A, is synthesized from a second
      spliced transcript which uses an alternative 3' acceptor site. In this study we
      used oligonucleotide-directed mutagenesis to confirm the positions of the B
      initiation codon and the 3' acceptor sites for the alternatively spliced B/C and
      A protein messages. We also located definitively the protein A initiation codon,
      an AUG triplet mapping to nucleotide 2203. Mutagenesis of the B initiator
      permitted a direct test of the effect of increased B initiator strength on the
      translational efficiencies of the B and C proteins. It was found that conversion
      of the relatively inefficient protein B initiator (ACG) to an AUG enhanced the
      level of B synthesis while abolishing the synthesis of C from its downstream AUG
      initiator. Protein C synthesis thus depends on the strength of the B initiator,
      i.e., the relatively higher levels of C (approximately 20-fold greater than B)
      must result from frequent readthrough of the weak B initiator. Finally, we
      examined the abilities of mutants deficient in the synthesis of A, B, or C to
      produce infectious virions. We found that at least two of the structural
      proteins, B and C, are required for the production of infectious virions and that
      sequestration of single-stranded adeno-associated virus genomes from the pool of
      replicating DNA molecules does not occur in the absence of either of these
      proteins.

PMID- 8254727
TI  - Studies of the major reovirus core protein sigma 2: reversion of the assembly
      defective mutant tsC447 is an intragenic process and involves back mutation of
      Asp-383 to Asn.
AB  - The reovirus group C temperature-sensitive mutant tsC447, whose defect maps to
      the S2 gene, which encodes the major core protein sigma 2, fails to assemble core
      particles at the nonpermissive temperature. To identify other proteins that may
      interact with sigma 2 during assembly, we generated and examined 10 independent
      revertants of the mutant. To determine which gene(s) carried a compensatory
      suppressor mutation(s), we generated intertypic reassortants between wild-type
      reovirus serotype 1 Lang and each revertant and determined the temperature
      sensitivities of the reassortants by efficiency-of-plating assays. Results of the
      efficiency-of-plating analyses indicated that reversion of the tsC447 defect was
      an intragenic process in all revertants. To identify the region(s) of sigma 2
      that had reverted, we determined the nucleotide sequences of the S2 genes. In all
      revertant sequences examined, the G at nucleotide position 1166 in tsC447 had
      reverted to the A present in the wild-type sequence. This reversion leads to the
      restoration of a wild-type asparagine (in place of a mutant aspartic acid) at
      amino acid 383 in the sigma 2 sequence. These results collectively indicate that
      the functional lesion in tsC447 is Asp-383 and that this lesion cannot be
      corrected by alterations in other core proteins. These observations suggest that
      this region of sigma 2, which may be important in mediating assembly of the core
      particle, does not interact significantly with other reovirus proteins.

PMID- 8254728
TI  - Selective sites of adenovirus (foreign) DNA integration into the hamster genome:
      changes in integration patterns.
AB  - We investigated whether, upon the integration of multiple copies of adenovirus
      type 12 (Ad12) DNA into an established mammalian (hamster) genome, the pattern of
      foreign DNA insertion would remain stable or change with consecutive passages of
      cells in culture. By the injection of purified Ad12 into newborn hamsters, tumors
      were induced, cells from these tumors were cultivated, and five independent cell
      lines, HT5, H201/2, H201/3, H271, and H281, were established. These cell lines
      carried different copy numbers of Ad12 DNA per cell in an integrated form and
      differed in morphology. Cell line HT5 had been passed twice through hamsters as
      tumor cells and was subsequently passaged in culture. Patterns of Ad12 DNA
      integration were determined by restriction cleavage of the nuclear DNA with
      BamHI, EcoRI, HindIII, MspI, or PstI followed by Southern blot hybridization
      using 32P-labeled Ad12 DNA or its cloned terminal DNA fragments as hybridization
      probes. In this way, the off-size fragments, which represented the sites of
      linkage between Ad12 and cellular DNAs, were determined. At early passage levels
      in culture, the integration sites of Ad12 DNA in the hamster genome, as
      characterized by the positions of off-size fragments in agarose or polyacrylamide
      gel electrophoresis, were different in the five different tumor cell lines. Upon
      repeated passage, however, the off-size fragment patterns generated by the five
      restriction endonucleases became very similar in the five tumor cell lines. This
      surprising result indicates that under cell culture conditions, Ad12-transformed
      tumor cell lines that carry the foreign (Ad12) genome in selective, probably very
      similar sites of the cellular genome evolve.

PMID- 8254729
TI  - Augmentation of pathogenesis of coxsackievirus B3 infections in mice by exogenous
      administration of interleukin-1 and interleukin-2.
AB  - Two variants of coxsackievirus B3 (CVB3) which differ dramatically in the ability
      to induce myocarditis in BALB/c mice were studied. H3 virus infection of murine
      monocytes in vitro resulted in release of concentrations of interleukin 1 (IL-1)
      and alpha/beta interferon that were high compared with those of cells infected
      with the H310A1 virus variant. In vivo, H3 virus infection caused substantial
      inflammatory cell infiltration of the myocardium, and lymphocytes from these
      animals gave predominantly Th1-cell responses to either whole H3 virus or
      overlapping peptides of the CVB3 vp1 capsid protein, as determined by IL-2
      production. In contrast, H310A1 virus infection produced minimal myocarditis and
      Th1-cell responses, but Th2-cell activation was more pronounced than in H3 virus
      infected mice (as determined by IL-4 concentrations). Exogenous treatment of
      H310A1 virus-infected mice with either IL-1 or IL-2 restored both myocarditis
      susceptibility and Th1-cell responses to whole virus and vp1 peptides.
      Furthermore, H310A1 virus-infected mice given exogenous IL-1 showed substantial
      in situ IL-2 deposition in the myocardium. These results indicate that CVB3
      induced myocarditis may depend upon release of specific cytokines during
      infection and that activation of Th1 cells may be an important factor in
      pathogenesis.

PMID- 8254730
TI  - One retroviral RNA is sufficient for synthesis of viral DNA.
AB  - We used previously characterized spleen necrosis virus-based retroviral vectors
      and helper cells to study the strand transfers that occur during the reverse
      transcription phase of a single cycle of retroviral replication. The conditions
      used selected only for formation of an active provirus rather than for expression
      of multiple drug resistance markers. In nonrecombinant proviruses the minus- and
      plus-strand DNA primer transfers were almost completely intramolecular. However,
      as previously reported, recombinant proviruses contained approximately equal
      proportions of inter- and intramolecular minus-strand DNA primer transfers. Thus,
      we conclude that in the absence of recombination, one molecule of retroviral RNA
      is sufficient for viral DNA synthesis. Large deletions and deletions with
      insertions were detected primarily at a limited number of positions which appear
      to be hot spots for such events, the primer binding site and regions containing
      multiple inverted repeats. At these hot spots, the rate of deletions and
      deletions with insertions visible with PCR was about 10% per genome per
      replication cycle. Other deletions and deletions with insertions (detectable with
      PCR) occurred at a rate of about 0.5%/kb per replication cycle. Crossovers
      occurred at a rate of about 6%/kb per replication cycle under single-selection
      conditions. This rate is comparable to the rate that we reported previously under
      double-selection conditions, indicating that retroviral homologous recombination
      is not highly error prone. The combined rates of deletions and deletions with
      insertions at hot spots (10% per genome per replication cycle) and other sites
      (0.5%/kb per replication cycle) and the rate of crossovers (6%/kb per replication
      cycle) indicate that on average, full-size (10-kb) type C retroviruses undergo an
      additional or aberrant strand transfer about once per cycle of infection.

PMID- 8254731
TI  - Regulation of JC virus expression in B lymphocytes.
AB  - The etiologic agent of progressive multifocal leukoencephalopathy, a subacute
      demyelinating disease of the central nervous system, is the human polyomavirus JC
      virus (JCV), which causes a lytic infection of myelin-producing oligodendrocytes.
      In infected individuals the JCV genome can be detected in brain tissue and B
      lymphocytes isolated from the blood, bone marrow, or lymph nodes. Using mobility
      shift assays and a radiolabeled oligonucleotide from the JCV promoter-enhancer
      region (JCV bp 130 to 160), referred to as domain B, we were able to detect
      specific bands of the same mobility in nuclear extracts from human fetal glial
      cells, U-251 glioma cells, different B-cell lines, and in vitro-activated
      tonsillar B lymphocytes but not from T cells. In addition, a specific shift was
      detected when using nuclear extracts from freshly isolated tonsillar or lymph
      node B cells from five AIDS patients, two of whom later developed progressive
      multifocal leukoencephalopathy. Somewhat surprisingly, the above gel shift was
      partially inhibited by unlabeled oligonucleotides containing a kappa E2-binding
      site. UV cross-linking of the protein-DNA complex from either B cells or glial
      cells and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      revealed the presence of a 46-kDa band. Transient transfection of a reporter
      plasmid constructed by fusing a trimer of the domain B sequence to a minimal
      promoter revealed activity in B lymphocytes and glial cells but not in T cells.
      Mutational analysis of this region demonstrated that the core TGGC repeat was
      essential for enhancer activity. Thus, a similar protein in B lymphocytes and
      glial cells may account for the preferential replication of JCV in these two cell
      types.

PMID- 8254732
TI  - Electron microscopy of the nucleocapsid from disrupted Moloney murine leukemia
      virus and of associated type VI collagen-like filaments.
AB  - To analyze the constituents of retroviruses, the Moloney murine leukemia virus
      was disrupted and observed by dark-field electron microscopy. Virus disruption
      was achieved by several methods: osmotic shock, freezing-thawing cycles, and
      exposure to urea up to 4 M, to NaCl up to 1 M, and to Triton X-100. Several
      components associated with broken Moloney murine leukemia virus were repeatedly
      found in preparations. These components have been described as rings, thick
      filaments, chain-like filaments, threads covered with proteins, threads with
      buckles, and naked threads. A quantitative analysis of the occurrence of these
      components has been carried out. Among them, the thick filaments composed of a
      compact helical arrangement of small beads 5 nm in diameter were considered to
      represent the nucleocapsid. The protease-sensitive buckles found on some threads
      could be a compact form of the viral RNA associated to the nucleocapsid protein
      NCp10. The RNase-sensitive naked threads are interpreted as the deproteinized
      viral RNA itself. The ubiquitous chain-like filaments possess a periodic
      structure identical to that of polymerized type VI collagen. It is proposed that
      this adhesive protein is associated with the viral envelope taken from the cell
      membrane during the budding process of retroviruses.

PMID- 8254733
TI  - Generation and characterization of a human immunodeficiency virus type 1 (HIV-1)
      mutant resistant to an HIV-1 protease inhibitor.
AB  - A synthetic peptide, RPI 312, that specifically inhibits the protease of the
      human immunodeficiency virus type 1 (HIV-1) showed a potent inhibition on virus
      production, maturation, and infectivity. Treatment with this agent prevented the
      cleavage of Gag protein at the site between p17 and p24 in HIV-1 chronically
      infected MOLT-4 cells as well as in the released virus. Passage of HIV-1 in the
      presence of gradually increasing concentrations of this protease inhibitor
      resulted in emergence of a variant that could evade the drug effects. In the
      resistant variant the maturation of Gag proteins appeared normal, but its
      infectivity was reduced compared with that of the parent virus. The nucleotides
      coding the amino acids at and around the cleavage site between Gag proteins p17
      and p24 were not changed. One point mutation (A-->G) at site 2082 of the pol gene
      that resulted in one amino acid change at site 84 of the protease from isoleucine
      to valine (I-84-->V) could be detected in the resistant variant. An HIV-1
      infectious DNA clone with the I-84-->V mutation also showed reduced sensitivity
      to this protease inhibitor. The findings that the resistant variant had lower
      infectivity and was still affected by higher doses of the drug support the
      speculation that resistance to protease inhibitors may not be as problematic as
      other drug resistance.

PMID- 8254734
TI  - Proteolytic activity of novel human immunodeficiency virus type 1 proteinase
      proteins from a precursor with a blocking mutation at the N terminus of the PR
      domain.
AB  - The mature human immunodeficiency virus type 1 proteinase (PR; 11 kDa) can cleave
      all interdomain junctions in the Gag and Gag-Pol polyprotein precursors. To
      determine the activity of the enzyme in its precursor form, we blocked release of
      mature PR from a truncated Gag-Pol polyprotein by introducing mutations into the
      N-terminal Phe-Pro cleavage site of the PR domain. The mutant precursor
      autoprocessed efficiently upon expression in Escherichia coli. No detectable
      mature PR was released; however, several PR-related products ranging in size from
      approximately 14 to 18 kDa accumulated. Products of the same size were generated
      when mutant precursors were digested with wild-type PR. Thus, PR can utilize
      cleavage sites in the region upstream of the PR domain, resulting in the
      formation of extended PR species. On the basis of active-site titration, the PR
      species generated from mutated precursor exhibited wild-type activity on peptide
      substrates. However, the proteolytic activity of these extended enzymes on
      polyprotein substrates provided exogenously was low when equimolar amounts of
      extended and wild-type PR proteins were compared. Mammalian cells expressing the
      mutated precursor produced predominantly precursor and considerably reduced
      amounts of mature products. Released particles consisted mostly of uncleaved or
      partially cleaved polyproteins. Our results suggest that precursor forms of PR
      can autoprocess but are less efficient in processing of the Gag precursor for
      formation of mature virus particles.

PMID- 8254735
TI  - Inhibition of human immunodeficiency virus type 1 Tat-dependent activation of
      translation in Xenopus oocytes by the benzodiazepine Ro24-7429 requires trans
      activation response element loop sequences.
AB  - Two benzodiazepine compounds, [7-chloro-5-(2-pyrryl)-3H-1,4 benzodiazapin-2-(H)
      one] (Ro5-3335) and [7-chloro-5-(1H-pyrrol-2-yl)-3H-benzo[e] [1,4] diazepin-2-yl]
      methylamine (Ro24-7429), inhibit human immunodeficiency virus type 1 (HIV-1)
      replication via a specific effect on the function of the transactivator protein,
      Tat. To gain further insight into the mechanism of action of these compounds, we
      have tested their effects in an alternative assay for Tat activation in Xenopus
      oocytes. In this system, translation of trans-activation response element (TAR)
      containing RNA is activated by Tat. Both compounds specifically blocked
      activation of translation in a dose-dependent fashion, with Ro24-7429 showing the
      greater potency. In the Xenopus oocyte system, as in mammalian cells, mutation of
      the TAR loop sequences abolishes Tat action. However, it is possible to obtain
      TAR-specific, Tat-dependent activation of a target RNA with a mutation in the
      loop provided that this target is in large excess. This result has been
      interpreted as indicating that a negative factor has been titrated (M. Braddock,
      R. Powell, A.D. Blanchard, A.J. Kingsman, and S.M. Kingsman, FASEB J. 7:214-222,
      1993). Interestingly Ro24-7429 was unable to inhibit the TAR-specific but loop
      sequence-independent mode of translational activation. This finding suggests that
      a specific loop-binding cellular factor may mediate the effects of this inhibitor
      of Tat action. Consistent with this notion, we could not detect any effect of
      Ro24-7429 on the efficiency of specific Tat binding to TAR in vitro.

PMID- 8254736
TI  - The nonstructural glycoprotein of rotavirus affects intracellular calcium levels.
AB  - Rotavirus infection of monkey kidney cells has been reported to result in a
      significant increase in the concentration of intracellular calcium. This increase
      in intracellular calcium was associated with viral protein synthesis and
      cytopathic effects in infected cells. We tested the effect of individual
      rotavirus proteins on intracellular calcium concentrations in insect Spodoptera
      frugiperda (Sf9) cells. Insect cells were infected with wild-type baculovirus or
      baculovirus recombinants that contained an individual rotavirus gene. The cells
      were harvested at different times postinfection, and the intracellular calcium
      concentration was measured by using fura-2 as a fluorescent calcium indicator. We
      found that the concentration of intracellular calcium was increased nearly
      fivefold in infected Sf9 cells that expressed the nonstructural glycoprotein
      (NSP4) of group A rotavirus, and this increase in intracellular calcium
      concentration coincided with NSP4 expression. A similar result was observed in
      insect cells expressing NSP4 from a group B rotavirus, suggesting the
      conservation of this function among rotavirus groups. Expression of the other 10
      rotavirus proteins or of wild-type baculovirus proteins in Sf9 cells did not
      significantly increase intracellular calcium levels. These results suggest that
      the nonstructural glycoprotein NSP4 is responsible for the increase in cytosolic
      calcium observed in rotavirus-infected cells.

PMID- 8254737
TI  - Assay for evaluation of rotavirus-cell interactions: identification of an
      enterocyte ganglioside fraction that mediates group A porcine rotavirus
      recognition.
AB  - A virus-host cell-binding assay was developed and used to investigate specific
      binding between group A porcine rotavirus and MA-104 cells or porcine
      enterocytes. A variety of glycoconjugates and cellular components were screened
      for their ability to block rotavirus binding to cells. During these experiments a
      crude ganglioside mixture was observed to specifically block rotavirus binding.
      On the basis of these results, enterocytes were harvested from susceptible
      piglets and a polar lipid fraction was isolated by solvent extraction and
      partitioning. Throughout subsequent purification of this fraction by Sephadex
      partition, ion-exchange, silicic acid, and thin-layer chromatography, blocking
      activity behaved as a monosialoganglioside (GMX) that displayed a thin-layer
      chromatographic mobility between those of GM2 and GM3. The blocking activity of
      GMX was inhibited by treatment with neuraminidase and ceramide glycanase but not
      by treatment with protease or heat (100 degrees C). Further purification of GMX
      by high-pressure liquid chromatography resulted in the resolution of two
      monosialogangliosides, GMX and a band which comigrated with GM1 on thin-layer
      chromatography. These data suggest that a cell surface monosialoganglioside or
      family of monosialogangliosides may function as an in vivo relevant receptor for
      group A porcine rotavirus and that sialic acid is a required epitope for virus
      binding activity.

PMID- 8254738
TI  - T-antigen kinase inhibits simian virus 40 DNA replication by phosphorylation of
      intact T antigen on serines 120 and 123.
AB  - Simian virus 40 (SV40) DNA replication begins after two large T-antigen hexamers
      assemble on the viral minimal origin of replication and locally unwind the
      template DNA. The activity of T antigen in this reaction is regulated by its
      phosphorylation state. A form of casein kinase I purified from HeLa nuclear
      extracts (T-antigen kinase) phosphorylates T antigen on physiologic sites and
      inhibits its activity in the unwinding reaction (A. Cegielska and D. M. Virshup,
      Mol. Cell. Biol. 13:1202-1211, 1993). Using a series of mutant T antigens
      expressed by recombinant baculoviruses in Sf9 cells, we find that the origin
      unwinding activities of both TS677-->A and TS677,679-->A are inhibited by the T
      antigen kinase, as is wild-type T antigen. In contrast, mutants TS120-->A and
      TS123,679-->A are resistant to inhibition by the kinase. Thus, phosphorylation of
      serines 120 and 123 is necessary for inhibition of T-antigen activity. Previous
      studies of casein kinase I substrate specificity have suggested that acidic
      residues or a phosphorylated amino acid amino terminal to the target residue are
      required to create a casein kinase I recognition site. However, we find that the
      T-antigen kinase can add more than 3 mol of Pi per mol to full-length bacterially
      produced T antigen and that it inhibits the unwinding activity of p34cdc2
      activated bacterially produced T antigen. Since no prior phosphorylation is
      present in this bacterially produced T antigen, and no acidic residues are
      present immediately amino terminal to serines 120 and 123, other structural
      elements of T antigen must contribute to the recognition signals for T-antigen
      kinase. In support of this conclusion, we find that while T-antigen kinase
      phosphorylates amino-terminal residues in bacterially produced full-length T
      antigen, it cannot phosphorylate bacterially produced truncated T antigen
      containing amino acids 1 to 259, a 17-kDa amino-terminal tryptic fragment of T
      antigen, nor can it phosphorylate denatured T antigen. These findings strongly
      suggest that the carboxy-terminal domain of T antigen is an important modifier of
      the recognition signals for phosphorylation of the critical amino-terminal sites
      by the T-antigen kinase. This conclusion is consistent with previous studies
      suggesting close apposition of amino- and carboxy-terminal domains of T antigen
      in the native protein. The three-dimensional conformation of the substrate
      appears to make a significant contribution to T-antigen kinase substrate
      specificity.

PMID- 8254739
TI  - Inducible and cell type-specific expression of VL30 U3 subgroups correlate with
      their enhancer design.
AB  - The murine VL30 elements constitute one family of retrotransposons represented in
      100 to 200 copies that are dispersed among the mouse chromosomes. On the basis of
      sequence homology, we have subdivided mouse VL30 members into four distinct U3
      subgroups. The use of subgroup-specific probes in Northern (RNA) blot analyses
      shows that individual VL30 U3 subgroups are expressed in a tissue-specific
      manner. We show by in situ hybridization of mouse skin treated with 12-O
      tetradecanoylphorbol-13-acetate (TPA) that VL30 expression is induced in
      epidermal keratinocytes but not in dermal fibroblasts. Transient transfections of
      reporter gene plasmids together with in vitro binding analysis indicate that TPA
      induced VL30 transcription specific for keratinocytes is mediated by two
      cooperating sequence motifs in juxtaposed position. One sequence motif is shown
      to constitutively bind CREB- and Jun-related proteins in both keratinocytes and
      fibroblasts, whereas the other is a target for TPA-induced c-Rel/p65(NF-kappa B)
      binding activity specifically in keratinocytes. These binding sites are found to
      be conserved within U3 subgroups and individual U3 regions showing induced
      expression in TPA-treated mouse epidermis. These results together with a sequence
      comparison between different U3 subgroups indicate that cell type-specific
      activity of transcription factors known to regulate VL30 transcription and the
      presence or absence of their cognate binding sites within individual U3 regions
      determine inducible and cell type-specific VL30 expression. The variable VL30 U3
      regions might thus be useful tools to study inducible and cell type-specific
      transcription in many different cell systems.

PMID- 8254740
TI  - Restoration of cytomegalovirus antigen presentation by gamma interferon combats
      viral escape.
AB  - An immediate-early protein of murine cytomegalovirus (MCMV), pp89, elicits an
      immunodominant and protective major histocompatibility complex (MHC) class I Ld
      restricted CD8+ T-lymphocyte response. Remarkably, presentation of the naturally
      processed peptide of pp89, the nonapeptide YPHFMPTNL, is abolished during
      permissive MCMV infection in vitro. This defect in pp89 presentation is due to
      the expression of MCMV early gene functions that specifically block the transport
      of peptide-charged MHC class I complexes to the cell surface (M. Del Val, H.
      Hengel, H. Hacker, U. Hartlaub, T. Ruppert, P. Lucin, and U. H. Koszinowski, J.
      Exp. Med. 176:729-738, 1992). Here, we demonstrate that MCMV-specific CD8+ T
      lymphocytes can reconstitute pp89 presentation in a parakrine fashion. The
      lymphocytes mediate the restoration of antigen presentation by MCMV-infected
      cells by releasing gamma interferon (IFN-gamma). IFN-gamma has no effect on
      synthesis and stability of the viral antigen pp89 nor does it interfere with the
      expression of viral early genes and their inhibitory effect on MHC class I
      molecular maturation. IFN-gamma results in a 25-fold increase in the synthesis of
      MHC class I molecules and a similar increase in the abundance of pp89-derived
      peptide. Many of the MHC molecules remain retained by the viral effect, but a
      surplus of MHC molecules escapes the effect and provides the effective surface
      presentation of the peptide. Adoptive cell transfer studies demonstrate the IFN
      gamma dependence of CD8+ T-lymphocyte function in vivo. Altogether, these data
      reconcile the paradoxical findings of an impaired pp89 presentation in vitro in
      parallel with pp89-specific CD8+ T-cell protection in vivo. The results also
      imply a role of IFN-gamma in the T-lymphocyte-mediated control of cytomegalovirus
      infection. The known propensity of cytomegalovirus to cause serious disease in
      the immunocompromised host is discussed in the light of these findings.

PMID- 8254741
TI  - Differential role of long terminal repeat control elements for the regulation of
      basal and Tat-mediated transcription of the human immunodeficiency virus in
      stimulated and unstimulated primary human macrophages.
AB  - Primary human macrophages induced to differentiate through contact with
      autologous activated nonadherent cells were used to investigate the
      transcriptional mechanisms involved in reactivation of human immunodeficiency
      virus (HIV) replication. Through transient transfection experiments with an HIV
      long terminal repeat (LTR)-chloramphenicol acetyltransferase reporter construct,
      we show that macrophage differentiation results in a 20-fold upregulation of
      basal LTR activity. To identify sequence elements responsive to the
      differentiation process, point mutations introduced into the LTR were tested in
      differentiated and undifferentiated macrophages. Several elements were identified
      as positive regulators of basal transcription. TATA, Sp1, and NF-kappa B binding
      sites were the most influential. The low-affinity site for LBP-1 (UBP-1)
      functioned as a negative regulator of LTR activity in undifferentiated
      macrophages, but this influence was lost upon differentiation. When tat was
      cotransfected into the expression system, the requirement for LTR elements
      identified as important for positive regulation of basal transcription remained
      in undifferentiated macrophages. Interestingly, however, the mutations in
      positive control elements which debilitated activity in undifferentiated
      macrophages had no effect on LTR activity in differentiated macrophages. Thus, it
      appears that while HIV-LTR activity is highly dependent on cellular transcription
      factors in undifferentiated cells, in differentiated macrophages the viral
      protein Tat confers pliability on the LTR and facilitates autonomy from absolute
      cellular control mechanisms. In vivo, release from either positive or negative
      regulation via cellular proteins may facilitate reactivation of HIV in
      macrophages.

PMID- 8254742
TI  - v-rel induces expression of three avian immunoregulatory surface receptors more
      efficiently than c-rel.
AB  - The c-rel gene is a member of NF-kappa B/rel family of transcription factors that
      regulate expression of a variety of immunoregulatory molecules. The viral
      oncogene, v-rel, is a truncated and mutated form of the turkey c-rel gene
      expressed by reticuloendotheliosis virus, strain T. In this study, we
      demonstrated that three avian immunoregulatory receptors, major
      histocompatibility (MHC) antigens class I and class II as well as the interleukin
      2 receptor (IL-2R), were induced on the surface of splenic tumor cells isolated
      from chickens infected with reticuloendotheliosis virus, strain T. All cell lines
      derived from splenic tumors expressed these three proteins. Their expression also
      correlated with the appearance of endogenous c-rel during a graft-versus-host
      reaction. In vitro, both c-rel and v-rel induced MHC class I, MHC class II, and
      IL-2R on an avian B-lymphoid cell line, DT95, and a T-lymphoid cell line, MSB-1.
      Quantitative kinetic analysis demonstrated both the accumulation of MHC class II
      mRNA and the appearance of surface MHC class II protein in response to the
      synthesis of either v-rel or c-rel. We show that v-rel induced the expression of
      MHC class II in the avian B-cell lines DT40 and DT95 more rapidly than c-rel and
      that, several weeks after infection, v-rel induced MHC class II as much as 50
      fold more efficiently than c-rel. Finally, in vitro infection of splenocytes with
      retroviruses that express v-rel or c-rel induced MHC class I, MHC class II, and
      IL-2R expression. Quantitative analysis confirmed that p59v-rel was consistently
      more efficient at inducing expression of all three immunoregulatory receptors
      than exogenous p68c-rel. These data suggest that during tumor development, v-rel
      functions to induce (or suppress) the expression of genes similarly induced (or
      suppressed) by c-rel. The observations reported in this study are not in
      agreement with a model in which v-rel promotes tumor development by functioning
      as a dominant negative mutant of c-rel. In contrast, these findings support the
      hypothesis that lymphocyte immortalization and tumor development are the result,
      at least in part, of the capacity of v-rel to function as a dominant positive
      mutant that induces expression of genes normally regulated by c-rel.

PMID- 8254743
TI  - Identification of the threonine phosphorylation sites on the polyomavirus major
      capsid protein VP1: relationship to the activity of middle T antigen.
AB  - Phosphorylation of the polyomavirus major capsid protein VP1 was examined after
      in vivo 32P labeling of virus-infected cells. Two phosphorylated peptide
      fragments of VP1 were identified by protease digestion, high-performance liquid
      chromatography purification, mass spectrometry, and N-terminal sequencing. The
      peptides from residues 58 to 78 and residues 153 to 173 were phosphorylated on
      threonine. Site-directed mutations were introduced at these threonine sites, and
      mutant viruses were reconstructed. A threonine-to-glycine change at residue 63
      (mutant G63) and a threonine-to-alanine change at residue 156 (mutant A156)
      resulted in viruses defective in phosphorylation of the respective peptides after
      in vivo labeling. Growth of the mutant G63 virus was similar to that of the wild
      type virus, but the mutant A156 was inefficient in assembly of 240S viral
      particles. Polyomavirus nontransforming host range (hr-t) mutants are defective
      in VP1 threonine phosphorylation when grown in nonpermissive cells (R. L. Garcea,
      K. Ballmer-Hofer, and T. L. Benjamin, J. Virol. 54:311-316, 1985). Proteolytic
      mapping of VP1 peptides after in vivo labeling from hr-t mutant virus infections
      demonstrated that both residues T-63 and T-156 were affected. These results
      suggest that the block in virion assembly in hr-t mutant viruses is associated
      with a defect in phosphorylation of threonine 156.

PMID- 8254744
TI  - Optimization of targeted RNA recombination and mapping of a novel nucleocapsid
      gene mutation in the coronavirus mouse hepatitis virus.
AB  - We have recently described a method of introducing site-specific mutations into
      the genome of the coronavirus mouse hepatitis virus (MHV) by RNA recombination
      between cotransfected genomic RNA and a synthetic subgenomic mRNA (C. A.
      Koetzner, M. M. Parker, C. S. Ricard, L. S. Sturman, and P. S. Masters, J. Virol.
      66:1841-1848, 1992). By using a thermolabile N protein mutant of MHV (Alb4) as
      the recipient virus and synthetic RNA7 (the mRNA for the nucleocapsid protein N)
      as the donor, we selected engineered recombinant viruses as heat-stable progeny
      resulting from cotransfection. We have now been able to greatly increase the
      efficiency of targeted recombination in this process by using a synthetic
      defective interfering (DI) RNA in place of RNA7. The frequency of recombination
      is sufficiently high that, with Alb4 as the recipient, recombinants can be
      directly identified without using thermal selection. The synthetic DI RNA has
      been used to demonstrate that the lesion in another temperature-sensitive and
      thermolabile MHV mutant, Alb1, maps to the N gene. Sequencing of the Alb1 N gene
      revealed two closely linked point mutations that fall in a region of the N
      molecule previously noted as being the most highly conserved region among all of
      the coronavirus N proteins. Analysis of revertants of the Alb1 mutant revealed
      that one of the two mutations is critical for the temperature-sensitive
      phenotype; the second mutation is phenotypically silent.

PMID- 8254746
TI  - Requirement for double-strand breaks but not for specific DNA sequences in herpes
      simplex virus type 1 genome isomerization events.
AB  - Herpes simplex virus type 1 (HSV-1) genome isomerization occurs as a result of
      DNA replication-mediated homologous recombination between several sets of
      inverted repeat sequences present in the viral DNA. The frequency with which this
      recombination occurs has been demonstrated to be dependent upon DNA homology
      length rather than specific sequences. However, the smallest of the viral
      inverted repeats, the alpha sequence, has been shown to function as a
      recombinational hot spot, leading to speculation that this sequence may represent
      a specific element through which genome isomerization is mediated. To investigate
      this apparent paradox, a quantitative transient recombination assay system was
      developed and used to examine the recombinogenic properties of a panel of alpha
      sequence mutants. This analysis revealed that the presence of both the pac1 and
      pac2 elements was both necessary and sufficient for the induction of high
      frequency recombination events by the alpha sequence. However, it was the double
      strand break promoted by pac1 and pac2 during cleavage and packaging at the alpha
      sequence, and not the DNA sequences of the elements themselves, which appeared to
      be critical for recombination. This was illustrated (i) by the inability of the
      same pac1 and pac2 sequences to mediate inversion events in cells infected with
      an HSV-1 mutant which was competent for DNA replication-dependent recombination
      but defective for the cleavage and packaging process and (ii) by the ability of
      double-strand breaks generated in non-HSV-1 DNA by an in vivo-expressed
      restriction endonuclease to significantly stimulate the initiation of
      recombination events in virus-infected cells. Thus, the alpha sequence appears to
      act as a hot spot for homologous recombination simply because it happens to
      coincide with the site of the double-strand break which is generated during the
      cleavage and packaging process, not because it contains discrete sequences which
      are required for this activity. However, it was found that this enhanced
      recombinogenicity disappeared when the element was flanked by regions of
      extensive sequence homology, particularly that of the large inverted repeats
      which flank the alpha sequence at its natural site in the HSV-1 genome. These
      findings are consistent with a model for HSV-1 genome isomerization in which
      recombination is initiated primarily by multiple random double-strand breaks
      which arise during DNA replication across the inverted repeats of the genome,
      rather than by a single specific break which occurs at the alpha sequence during
      the cleavage and packaging process.

PMID- 8254745
TI  - Capsid assembly and involved function analysis of twelve core protein mutants of
      duck hepatitis B virus.
AB  - The roles of different regions of the duck hepatitis B virus (DHBV) core protein
      on viral capsid assembly and related functions were examined. Twelve deletion and
      insertion mutations which covered 80% of the DHBV C open reading frame were
      constructed and expressed in Escherichia coli. The N-terminal region (amino acids
      3 to 66) of DHBV core protein was important for its tertiary structure and
      function in E. coli. The expressed core mutants without this region apparently
      inhibited E. coli growth. The results of transmission electron microscopy of E.
      coli thin sections, capsid agarose gel, and sucrose gradient sedimentation
      demonstrated that a few DHBV core mutants with insertion in the N terminus and
      deletion in the C terminus retained the ability to form core-like particles in E.
      coli. However, other mutations in most of N-terminal and central regions strongly
      inhibited the self-assembly ability of DHBV core protein in E. coli. In addition,
      the mutant with a C-terminal region deletion (amino acids 181 to 228) lost most
      of the nucleic acid-binding activity of the DHBV core protein.

PMID- 8254747
TI  - A single chicken anemia virus protein induces apoptosis.
AB  - Chicken anemia virus (CAV) causes cytopathogenic effects in chicken thymocytes
      and cultured transformed mononuclear cells via apoptosis. Early after infection
      of chicken mononuclear cells, the CAV-encoded protein VP3 exhibits a finely
      granular distribution within the nucleus. At a later stage after infection, VP3
      forms aggregates. At this point, the cell becomes apoptotic and the cellular DNA
      is fragmented and condensed. By immunogold electron microscopy VP3 was shown to
      be associated with apoptotic structures. In vitro, expression of VP3 induced
      apoptosis in chicken lymphoblastoid T cells and myeloid cells, which are
      susceptible to CAV infection, but not in chicken embryo fibroblasts, which are
      not susceptible to CAV. Expression of a C-terminally truncated VP3 induced much
      less pronounced apoptosis in the chicken lymphoblastoid T cells.

PMID- 8254748
TI  - Synthesis of viruslike particles by expression of the putative capsid protein of
      Leishmania RNA virus in a recombinant baculovirus expression system.
AB  - The putative capsid open reading frame (ORF2) of the Leishmania RNA virus LRV1-4
      was expressed in a baculovirus expression system. The expressed protein was
      identified by Western immunoblot analysis with polyclonal antiserum raised to
      purified LRV1-4 virus. Electron microscopy and sedimentation analysis indicated
      that the expressed protein self-assembles into empty viruslike particles of
      similar size and shape to authentic virus particles, thus confirming that ORF2
      encodes the viral capsid. The expressed particles are present exclusively in the
      cytoplasm of infected SF9 cells and are able to assemble in the absence of LRV1-4
      RNA, viral polymerase, or any Leishmania host factors.

PMID- 8254750
TI  - Nucleotide sequence of human adenovirus type 12 DNA: comparative functional
      analysis.
AB  - A fresh inoculum of human adenovirus type 12 (Ad12) was obtained from the
      American Type Culture Collection and passaged once on human embryonic kidney
      cells, and Ad12 DNA was prepared from the first-passage yield to avoid higher
      passages which might have generated host-virus DNA recombinants. The 18 PstI
      fragments of Ad12 DNA were cloned into the pBluescript KS vector, and the entire
      nucleotide sequence of both strands from all 18 fragments was determined by using
      successive oligodeoxyribonucleotide primers. Ad12 DNA extends over 34,125
      nucleotide pairs, and its molecular weight is calculated to be about 22 x 10(6).
      The nucleotide sequence of Ad12 DNA was subjected to computer analyses that
      determined possible open reading of frames on the two strands, the leader
      sequences, the position of the virus-associated RNA coding region, possible TATA,
      and polyadenylation signals. The distribution of the Ad12 open reading frames was
      similar to that in the previously sequenced Ad2 DNA, but there were also distinct
      differences. Ad12 DNA has an inverted terminal redundancy of 161 nucleotides,
      compared with 102 nucleotides in Ad2 DNA. There were stretches of sequence
      identity between Ad2 and Ad12 DNAs at both termini; the overall sequence
      similarity between the two viral genomes ranged between 59% (polypeptide IX) and
      77% (in the E2 region), with high homology also in the sequences for the
      adenovirus DNA polymerase.

PMID- 8254749
TI  - Retention by the endoplasmic reticulum of rotavirus VP7 is controlled by three
      adjacent amino-terminal residues.
AB  - The rotavirus outer capsid glycoprotein, VP7, is an endoplasmic reticulum (ER)
      membrane-associated glycoprotein in both infected and transfected cells. It was
      previously demonstrated in this laboratory and by others that both the cleaved
      signal sequence (H2) and the first NH2-terminal 61 amino acids of VP7 are
      sufficient and necessary for ER retention of this molecule. Using site-specific
      mutagenesis and transfection techniques, we show that residues Ile-9, Thr-10, and
      Gly-11 were specifically necessary for ER retention. These results further define
      the ER retention sequence of VP7 and demonstrate that conservative changes,
      apparently innocuous in only three adjacent amino acids, can lead to major
      solubility and compartmentalization changes. It was found that placement of the
      first 31 mature NH2-terminal residues of VP7, in addition to the cleaved ER
      translocation signal sequence, was sufficient to retain the enzymatically active
      chimeric alpha-amylase in the ER; this enzyme is normally secreted. Deletions of
      the residues Ile-9, Thr-10, and Gly-11 within the amylase chimera containing 31
      VP7 amino acids resulted in secretion of enzymatically active protein. It was
      also observed that the residues of VP7 presented in certain chimeras were able to
      abolish alpha-amylase enzymatic activity. These chimeras are presumably misfolded
      since it was demonstrated by pulse-chase experiments that these molecules are
      degraded in the ER. We surmise that a favorable conformation is necessary for
      retention since ER retention and activity of the chimeras depend on the primary
      sequence context.

PMID- 8254751
TI  - Epidermal growth factor (EGF) modulation of feline sarcoma virus fms tyrosine
      kinase activity, internalization, degradation, and transforming potential in an
      EGF receptor/v-fms chimera.
AB  - The feline sarcoma virus oncogene v-fms has significantly contributed to the
      dissection of peptide growth factor action since it encodes the transmembrane
      tyrosine kinase gp140v-fms, a transforming version of colony-stimulating factor 1
      receptor, a member of the growth factor receptor tyrosine kinase family. In this
      study, the functional significance of structural differences between distinct
      tyrosine kinase types, in particular between cellular receptors and viral
      transforming proteins of distinct structural types, has been further
      investigated, and their functional compatibility has been addressed. For this
      purpose, major functional domains of three structurally distinct tyrosine kinases
      were combined into two chimeric receptors. The cytoplasmic gp140v-fms kinase
      domain and the kinase domain of Rous sarcoma virus pp60v-src were each fused to
      the extracellular ligand-binding domain of the epidermal growth factor (EGF)
      receptor to create chimeras EFR and ESR, respectively, which were studied upon
      stable expression in NIH 3T3 fibroblasts. Both chimeras were faithfully
      synthesized and routed to the cell surface, where they displayed EGF-specific,
      low-affinity ligand-binding domains in contrast to the high- and low-affinity EGF
      binding sites of normal EGF receptors. While the EFR kinase was EGF controlled
      for autophosphorylation and substrate phosphorylation in vitro, in vivo, and in
      digitonin-treated cells, the ESR kinase was not responsive to EGF. While ESR
      appeared to recycle to the cell surface upon endocytosis, EGF induced efficient
      EFR internalization and degradation, and phorbol esters stimulated protein kinase
      C-mediated downmodulation of EFR. Despite its ligand-inducible kinase activity,
      EFR was partly EGF independent in mediating mitogenesis and cell transformation,
      while ESR appeared biologically inactive.

PMID- 8254752
TI  - Persistence of four related human immunodeficiency virus subtypes during the
      course of zidovudine therapy: relationship between virion RNA and proviral DNA.
AB  - Human immunodeficiency virus (HIV) virion RNA and proviral DNA sequences have
      been examined over a 1-year period in an HIV-seropositive patient, commencing
      with the start of zidovudine treatment. By characterizing the variable V3 and V4
      env domains, four related but structurally discrete genotypes could be identified
      prior to the start of therapy and during the subsequent 60-week period of
      therapy. Each of the four subtypes showed a unique pattern in the preservation of
      glycosylation sites. A comparison of the V3 amino acid sequences in peripheral
      blood mononuclear cell proviral DNA and plasma virion RNA at 0, 24, 36, and 60
      weeks demonstrated that proviral DNA did not serve as a predictor of the
      structure of virion RNA. HIV virion RNA subtype 3 was the most prevalent virion
      RNA subtype at three of the four periods studied, yet no corresponding proviral
      DNA was detected. Other virion subtypes have been observed, but only on a
      transient basis. The present data are consistent with a model of HIV infection in
      which related but different HIV substrains coexist and evolve independently
      within an individual. Characterization of virion RNA may be required to identify
      the unique properties of the virus involved in disease progression;
      characterization of proviral DNA will not yield this information.

PMID- 8254753
TI  - Induced extrusion of DNA from the capsid of herpes simplex virus type 1.
AB  - DNA-filled capsids (C capsids) of herpes simplex virus type 1 were treated in
      vitro with guanidine-HCl (GuHCl) and analyzed for DNA loss by sucrose density
      gradient ultracentrifugation and electron microscopy. DNA was found to be lost
      quantitatively from virtually all capsids treated with GuHCl at concentrations of
      0.5 M or higher, while 0.1 M GuHCl had little or no effect. DNA removal from 0.5
      M GuHCl-treated capsids was effected without significant change in the capsid
      protein composition, as judged by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, or in its structure, as judged by electron microscopy. Electron
      microscopic examination of capsids in the process of emptying showed that DNA was
      extruded from multiple, discrete sites which appeared to coincide with capsid
      vertices. DNA exited the capsid in the form of thick strands or fibers that
      varied in diameter from approximately 4 to 13 nm with preferred diameters of 7
      and 11 nm. The fibers most probably correspond to multiple, laterally aligned DNA
      segments, as their diameters are nearly all greater than that of a single DNA
      double helix. The results suggest that GuHCl treatment promotes an alteration in
      the capsid pentons which allows DNA to escape locally. Hexons must be more
      resistant to this change, since DNA loss appears to be restricted to the pentons.
      The ability of GuHCl to cause loss of DNA from C capsids with no accompanying
      change in capsid morphology or protein composition suggests that penton sites may
      open transiently to permit DNA exist and then return to their original state.

PMID- 8254754
TI  - Interactions of normal and mutant vesicular stomatitis virus matrix proteins with
      the plasma membrane and nucleocapsids.
AB  - We demonstrated recently that a fraction of the matrix (M) protein of vesicular
      stomatitis virus (VSV) binds tightly to cellular membranes in vivo when expressed
      in the absence of other VSV proteins. This membrane-associated M protein was
      functional in binding purified VSV nucleocapsids in vitro. Here we show that the
      membrane-associated M protein is largely associated with a membrane fraction
      having the density of plasma membranes, indicating membrane specificity in the
      binding. In addition, we analyzed truncated forms of M protein to identify
      regions responsible for membrane association and nucleocapsid binding. Truncated
      M protein lacking the amino-terminal basic domain still associated with cellular
      membranes, although not as tightly as wild-type M protein, and could not bind
      nucleocapsids. In contrast, deletion of the carboxy-terminal 14 amino acids did
      not disrupt stable membrane association or nucleocapsid interaction. These
      results suggest that the amino terminus of M protein either interacts directly
      with membranes and nucleocapsids or stabilizes a conformation that is required
      for M protein to mediate both of these interactions.

PMID- 8254755
TI  - Mapping the Flv locus controlling resistance to flaviviruses on mouse chromosome
      5.
AB  - Genetically determined resistance to flaviviruses in mice is a dominant trait
      conferred by alleles at a single autosomal locus designated Flv, but no gene
      products have been associated with this locus and the mechanism of resistance is
      not well understood. To further characterize this model of genetic resistance, we
      conducted mapping studies to determine the chromosomal location of Flv. Because
      of evidence suggesting that the Flv locus is on chromosome 5, three-point
      backcross linkage analyses were used to define the location of Flv relative to
      previously assigned chromosome 5 markers. The results confirm the chromosome 5
      location of Flv and indicate a map position between the anchor loci rd and Gus-s.
      The chromosomal localization of Flv is the first step in the production of a
      detailed linkage map of the Flv region, which may open approaches to positional
      cloning of the resistance gene.

PMID- 8254756
TI  - The adenovirus E3 14.7-kilodalton protein which inhibits cytolysis by tumor
      necrosis factor increases the virulence of vaccinia virus in a murine pneumonia
      model.
AB  - The 14.7-kilodalton protein (14.7K protein) encoded by the adenovirus (Ad) E3
      region inhibits tumor necrosis factor alpha (TNF-alpha)-mediated lysis of cells
      in tissue culture experiments, but the relevance of this effect in vivo is
      incompletely understood. To examine the effect of the ability of the Ad 14.7K
      protein to block TNF lysis upon viral pathogenesis in a murine model, we cloned
      the 14.7K protein-encoding gene into vaccinia virus (VV), permitting its study in
      isolation from other Ad E3 immunomodulatory proteins. The gene for murine TNF
      alpha was inserted into the same VV containing the 14.7K gene to ensure that each
      cell infected with the VV recombinant would express both the agonist (TNF) and
      its antagonist (14.7K). VV was utilized as the vector because it accommodates
      large and multiple inserts of foreign DNA with faithful, high-level expression of
      the protein products. In addition, infection of mice with VV induces disease with
      quantifiable morbidity, mortality, and virus replication. The results of
      intranasal infections of BALB/c mice with these VV recombinants indicate that the
      Ad 14.7K protein increases the virulence of VV carrying the TNF-alpha gene by
      reversing the attenuating effect of TNF-alpha on VV pathogenicity. This was
      demonstrated by increased mortality, pulmonary pathology, and viral titers in
      lung tissue following infection with VV coexpressing the 14.7K protein and TNF
      alpha, compared with the control virus expressing TNF-alpha alone. These results
      suggest that the 14.7K protein, which is nonessential for Ad replication in
      tissue culture, is an immunoregulatory protein which functions in vivo to help
      counteract the antiviral effects of TNF-alpha.

PMID- 8254757
TI  - Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked
      oligosaccharides.
AB  - The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein has been
      shown to be extensively modified by N-linked glycosylation; however, the presence
      of O-linked carbohydrates on the glycoprotein has not been firmly established. We
      have found that enzymatic deglycosylation of the HIV-1 envelope glycoprotein with
      neuraminidase and O-glycosidase results in a decrease in the apparent molecular
      weight of the envelope glycoprotein. This result was observed in both vaccinia
      virus recombinant-derived envelope glycoproteins and glycoproteins derived from
      the IIIB, SG3, and HXB2, strains of HIV-1. The decrease in molecular weight was
      also observed when the envelope glycoprotein had been deglycosylated with N
      glycanase F after treatment with neuraminidase and O-glycosidase, indicating that
      the decrease in apparent molecular weight was not attributable to the removal of
      N-linked carbohydrate. Treatment with neuraminidase, O-glycosidase, and N
      glycanase F was found to be necessary to remove all radiolabel from
      [3H]glucosamine-labelled envelope glycoprotein, a result seen for both
      recombinant and HIV-1-derived envelope glycoprotein. [3H]glucosamine-labelled
      carbohydrates liberated by O-glycosidase treatment were separated by paper
      chromatography and were found to be of a size consistent with O-linked
      oligosaccharides. We, therefore, conclude that the HIV-1 envelope glycoprotein is
      modified by the addition of O-linked carbohydrates.

PMID- 8254758
TI  - ICP34.5 mutants of herpes simplex virus type 1 strain 17syn+ are attenuated for
      neurovirulence in mice and for replication in confluent primary mouse embryo cell
      cultures.
AB  - In a recent report, the neurovirulence of herpes simplex virus type 1 (HSV-1) was
      mapped to the ICP34.5 gene (J. Chou, E. R. Kern, R. J. Whitley, and B. Roizman,
      Science 250:1262-1266, 1990). In this report, specific mutations within ICP34.5
      were constructed in HSV-1 strain 17syn+ to determine the effects of these
      mutations in a fully neurovirulent isolate. It was found that termination of the
      ICP34.5 gene after the N-terminal 30 amino acids resulted in a mutant, 17termA,
      which was 25- to 90-fold reduced in neurovirulence. This reduction of
      neurovirulence was associated with restricted replication of the mutant virus in
      mouse brain. The reduced replication phenotype was also evident in the trigeminal
      and dorsal root ganglia following inoculation at the periphery. 17termA was
      capable of replicating with wild-type kinetics in mouse footpads, and therefore
      the restriction seen in neural tissues was not due to a generalized replication
      defect in mouse cells. Significantly, replication of the mutant was also
      restricted in the mouse cornea in vivo and in confluent primary mouse embryo
      cells and mouse 10T1/2 cells in vitro. However, 17termA replicated with much
      greater efficiency in subconfluent mouse embryo cells, suggesting that the
      physiological state of the cell may be an important factor for productive
      replication of this mutant. Restoration of the ICP34.5 gene to the mutant
      resulted in a virus which displayed wild-type neurovirulence and replication
      kinetics in all cells and tissues tested.

PMID- 8254759
TI  - Identification of an 80-kilodalton membrane glycoprotein important for human T
      cell leukemia virus type I and type II syncytium formation and infection.
AB  - Human T-cell leukemia virus type I and type II (HTLV-I and HTLV-II, respectively)
      infect certain sublines of the BJAB human B-cell line. We observed that the WH
      subline, but not the CC/84 subline, of BJAB cells were infectible by cell-free
      HTLV-I or HTLV-II and formed syncytia with cells infected by these retroviruses.
      This suggests that the BJAB-CC/84 cells possibly lack a membrane molecule(s)
      important for syncytium formation and infectibility. In order to identify this
      antigen, we generated polyclonal anti-BJAB-WH antisera which were adsorbed on
      BJAB-CC/84 cells. The adsorbed antisera bound only BJAB-WH and BJAB-CC/79 cells
      as demonstrated by complement-dependent cytotoxicity and flow cytometric assays.
      Furthermore, this adsorbed antisera bound several human T-cell clones, including
      SupT-1, as determined by flow cytometric assays. The adsorbed antiserum was
      monospecific as it immunoprecipitated only one 78- to 80-kDa protein from lysates
      of metabolically labeled BJAB-WH, BJAB-CC/79, and SupT-1, but not BJAB-CC/84,
      cells. The monospecific antisera detected a glycoprotein composed of a 64- to 66
      kDa core protein containing tunicamycin-sensitive N-linked oligosaccharides. This
      membrane glycoprotein appears to be involved in HTLV-I- and HTLV-II-induced
      fusion and infection, as the monospecific antisera were capable of inhibiting
      both of these processes. The monospecific antisera diluted 1:50 and 1:90
      inhibited 85 to 90% of syncytium formation induced in BJAB-WH, BJAB-CC/79, and
      SupT-1 cells cultured with HTLV-I- or HTLV-II-infected MT2, MoT, or FLW human T-
      or B-cell lines. At the same dilution, antisera inhibited 70 to 80% of infection
      of BJAB-WH cells by cell-free HTLV-I or HTLV-II. Thus, these studies indicate a
      role for a 78- to 80-kDa glycoprotein in HTLV-I or HTLV-II infection and
      syncytium formation.

PMID- 8254760
TI  - Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis
      virus.
AB  - Genetic variation of the more complex retroviruses in the human T-cell leukemia
      virus/bovine leukemia virus (HTLV/BLV) group is less than in some other
      retroviral genera. To test whether reverse transcription of HTLV/BLV group
      members is less error prone than that of members of other groups, we developed an
      assay for detecting forward mutations in BLV, similar to that developed for the
      simpler spleen necrosis virus (SNV). We used this system to study the rates and
      types of mutations that occur during a single replication cycle. We found that
      BLV reverse transcription is approximately two and one-half times less error
      prone than SNV reverse transcription (4.8 x 10(-6) versus 1.2 x 10(-5) mutation
      per bp per cycle, respectively). The relative numbers of all types of observed
      mutations (that is, base pair substitutions, frameshifts, deletions, and
      deletions with insertions) were similar for BLV and SNV.

PMID- 8254761
TI  - Glycoprotein gB (gII) of pseudorabies virus can functionally substitute for
      glycoprotein gB in herpes simplex virus type 1.
AB  - Glycoproteins homologous to gB of herpes simplex virus (HSV) constitute the most
      highly conserved family of herpesvirus glycoproteins. All gB homologs analyzed so
      far have been shown to play essential roles in penetration and direct viral cell
      to-cell spread. In studies aimed at assessing whether the high sequence homology
      is also indicative of functional homology, we analyzed the ability of the gB
      homologous glycoprotein (former designation gII) of pseudorabies virus (PrV) to
      complement a gB- HSV type 1 (HSV-1) mutant and vice versa. The results show that
      a PrV gB-expressing cell line phenotypically complemented the lethal defect in gB
      HSV-1 whereas reciprocal complementation of a gB- PrV mutant by HSV-1 gB was not
      observed.

PMID- 8254762
TI  - Replication of human papillomavirus (HPV) DNAs supported by the HPV type 18 E1
      and E2 proteins.
AB  - Transient replication of human papillomavirus (HPV) type 18 DNA was shown to
      require the viral E1 and E2 proteins. A 108-bp sequence within the long control
      region (nucleotides 12 to 119) was sufficient to function as the origin, but
      maximal replication required a region of 177 bp from positions 7800 to 7857 and 1
      to 119 of HPV-18. The E1 and E2 proteins of HPV-18 also supported transient
      replication of plasmids containing the origins of HPV-1a and bovine
      papillomavirus type 1 to low levels. Interestingly, the level of replication
      observed with the HPV-6b origin was higher than that obtained with the homologous
      HPV-18 origin.

PMID- 8254763
TI  - Passage through mitosis is required for oncoretroviruses but not for the human
      immunodeficiency virus.
AB  - The human immunodeficiency virus productively infects and integrates into cells
      that have been arrested in the cell cycle with either gamma irradiation or
      aphidicolin. Integration by oncoretroviruses such as the murine leukemia virus
      (MuLV), on the other hand, depends on cell proliferation. Although the entire
      cell cycle is not necessary for MuLV infection, it is essential that the infected
      cells pass through mitosis. The long terminal repeat circle junction, a marker
      for nuclear entry, is first observed in MuLV-infected cells immediately after
      mitosis. These results suggest that mitosis is necessary for nuclear entry of
      MuLV, but not human immunodeficiency virus, unintegrated proviral DNA.

PMID- 8254764
TI  - Protection against the mouse-adapted A/FM/1/47 strain of influenza A virus in
      mice by a monoclonal antibody with cross-neutralizing activity among H1 and H2
      strains.
AB  - The monoclonal antibody designated C179 was found to neutralize all of the H1 and
      H2 strains of influenza A virus studied (Y. Okuno, Y. Isegawa, F. Sasao, and S.
      Ueda, J. Virol. 67:2552-2558, 1993). In the present study, the ability of C179 to
      protect mice from the lethal effect of the A/FM/1/47 (H1N1) strain was examined.
      When the mice were injected intraperitoneally with 100 micrograms of C179 per
      mouse a day before the virus challenge (2.0 x 10(3) focus-forming units per
      mouse), all of the mice survived. Moreover, significantly higher survival rates
      were observed in mice receiving 1,000 micrograms of C179 per mouse 2 days after
      the virus challenge than in those receiving phosphate-buffered saline alone.
      These results indicate that C179 is effective not only for prevention but also
      for treatment of mice infected with H1 and H2 strains. The possibility that C179
      can be used for passive immunization in humans is discussed.

PMID- 8254765
TI  - Retention of the herpes simplex virus type 1 (HSV-1) UL37 protein on single
      stranded DNA columns requires the HSV-1 ICP8 protein.
AB  - The UL37 and ICP8 proteins present in herpes simplex virus type 1 (HSV-1)
      infected-cell extracts produced at 24 h postinfection coeluted from single
      stranded-DNA-cellulose columns. Experiments carried out with the UL37 protein
      expressed by a vaccinia virus recombinant (V37) revealed that the UL37 protein
      did not exhibit DNA-binding activity in the absence of other HSV proteins.
      Analysis of extracts derived from cells coinfected with V37 and an ICP8
      expressing vaccinia virus recombinant (V8) and analysis of extracts prepared from
      cells infected with the HSV-1 ICP8 deletion mutants d21 and n10 revealed that the
      retention of the UL37 protein on single-stranded DNA columns required a DNA
      binding-competent ICP8 protein.

PMID- 8254766
TI  - Investigation of the specificity of the herpes simplex virus type 1 protease by
      point mutagenesis of the autoproteolysis sites.
AB  - The herpes simplex virus type 1 (HSV-1) protease is cleaved at two autoprocessing
      sites during viral maturation, one of which shares amino acid identity with its
      substrate, ICP35. Similar autoprocessing sites have been observed within other
      members of the Herpesviridae. Introduction of point mutations within the
      autoprocessing sites of the HSV-1 protease indicated that specificity resides
      within the P4-P1' region of the cleavage sites.

PMID- 8254767
TI  - The influenza virus variant A/FM/1/47-MA possesses single amino acid replacements
      in the hemagglutinin, controlling virulence, and in the matrix protein,
      controlling virulence as well as growth.
AB  - Genetic analysis of mouse-adapted influenza virus variant A/FM/1/47 (FM) MA has
      previously identified four genome segments, 4, 5, 7, and 8, that are
      statistically associated with virulence. On sequencing these genome segments, we
      found single amino acid replacements at amino acid 47 of the HA2 subunit of the
      hemagglutinin and at amino acid 139 of the matrix protein. Mutation was not
      detected in segments 5 and 8, obviating a role for these genes in FM-MA
      virulence. FM-MA replicates to higher titer than FM in MDCK cells and in mouse
      lung. FM X FM-MA reassortants were used to show that the M1 gene controlled
      replication in MDCK cells as well as in mouse lung.

PMID- 8254768
TI  - Restriction and enhancement of human immunodeficiency virus type 1 replication by
      modulation of intracellular deoxynucleoside triphosphate pools.
AB  - Human immunodeficiency virus type 1 (HIV-1) replication is shown to be sensitive
      to the intracellular concentration of deoxynucleoside triphosphate substrates.
      Addition of thymidine to established cell lines resulted in a dramatic reduction
      of virus production. The effect could be substantially alleviated by addition of
      deoxycytidine, which, alone, enhanced viral titers by a factor of 2 to 3.
      Hydroxyurea treatment abolished HIV-1 replication in peripheral blood mononuclear
      cells and could be reversed by deoxyadenosine. These data show that HIV-1
      replication occurs under suboptimal DNA precursor conditions.

PMID- 8254770
TI  - Nucleotide sequence of wild-type hepatitis A virus GBM in comparison with two
      cell culture-adapted variants.
AB  - In order to study cell tropism and attenuation of hepatitis A virus (HAV), the
      genome of HAV wild-type GBM and two cell culture-adapted variants, GBM/FRhK and
      GBM/HFS, were cloned and sequenced after amplification by reverse transcriptase
      PCR. During virus cultivation, the HAV variant GBM/FRhK had a strict host range
      for FRhK-4 cells, in contrast to GBM/HFS, which can be grown in HFS and FRhK-4
      cells. The HAV variant GBM/HFS was shown to be attenuated when inoculated into
      chimpanzees (B. Flehmig, R. F. Mauler, G. Noll, E. Weinmann, and J. P. Gregerson,
      p. 87-90, in A. Zuckerman, ed., Viral Hepatitis and Liver Disease, 1988). On the
      basis of this biological background, the comparison of the nucleotide sequences
      of these three HAV GBM variants should elucidate differences which may be of
      importance for cell tropism and attenuation. The comparison of the genome between
      the GBM wild type and HAV wild types HM175 (J. I. Cohen, J. R. Ticehurst, R. H.
      Purcell, A. Buckler-White, and B. M. Baroudy, J. Virol. 61:50-59, 1987) and HAV
      LA (R. Najarian, O. Caput, W. Gee, S. J. Potter, A. Renard, J. Merryweather, G.
      Van Nest, and D. Dina, Proc. Natl. Acad. Sci. USA 82:2627-2631, 1985) showed a 92
      to 96.3% identity, whereas the identity was 99.3 to 99.6% between the GBM
      variants. Nucleotide differences between the wild-type and the cell culture
      adapted variants, which were identical in both cell culture-adapted GBM variants,
      were localized in the 5' noncoding region; in 2B, 3B, and 3D; and in the 3'
      noncoding region. Our result concerning the 2B/2C region confirms a mutation at
      position 3889 (C-->T, alanine to valine), which had been shown to be of
      importance for cell culture adaptation (S. U. Emerson, C. McRill, B. Rosenblum,
      S. M. Feinstone, and R. H. Purcell, J. Virol. 65:4882-4886, 1991; S. U. Emerson,
      Y. K. Huang, C. McRill, M. Lewis, and R. H. Purcell, J. Virol. 66:650-654, 1992),
      whereas other mutations differ from published HAV sequence data and may be cell
      specific. Further comparison of the two cell culture-adapted GBM variants showed
      cell-specific mutations resulting in deletions of six amino acids in the VP1
      region and three amino acids in the 3A region of the GBM variant GBM/FRhK.

PMID- 8254769
TI  - Absence of an essential regulatory influence of the adenovirus E1B 19-kilodalton
      protein on viral growth and early gene expression in human diploid WI38, HeLa,
      and A549 cells.
AB  - Mutations in the gene encoding the adenovirus (Ad) early region 1B 19-kDa protein
      (the 19K gene) result in multiple phenotypic effects upon infection of permissive
      human cells. It has been reported, for example, that Ad type 2 (Ad2) and Ad5 with
      mutations in the 19K gene (19K-defective mutants) have a marked growth advantage
      compared with wild-type virus in human diploid WI38 cells (E. White, B. Faha, and
      B. Stillman, Mol. Cell. Biol. 6:3763-3773, 1986), and it was proposed that this
      host range phenotype stems from the large increase in viral early gene expression
      reported to occur in the mutant-infected cells. These observations gave rise to
      the hypothesis that the 19-kDa protein (the 19K protein) normally functions as a
      negative regulator of Ad early gene expression and growth. We have tested this
      hypothesis and find that Ad5 and Ad12 wild-type viruses grow as efficiently as
      their respective 19K-defective mutants, in1 and dl337 and pm700 and in700, in
      WI38 and other human cell types. Neither the accumulation of E1A cytoplasmic
      mRNAs nor the synthesis of E1A and other viral early proteins in these cells is
      altered as a result of these mutations in the 19K gene, and we conclude that the
      19K protein does not play an essential role in regulating viral early gene
      expression or viral growth in human cells.

PMID- 8254771
TI  - Effect of vesicular stomatitis virus matrix protein on host-directed translation
      in vivo.
AB  - Vesicular stomatitis virus infection causes a rapid and potent inhibition of both
      host transcription and translation. Recently, the viral matrix (M) protein was
      shown to inhibit host-directed transcription in vivo in the absence of any other
      viral component (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). The
      goal of this study was to determine the effect of M protein on host-directed
      translation. In vitro-transcribed mRNAs encoding M protein and chloramphenicol
      acetyltransferase (CAT) were cotransfected into BHK cells to determine the effect
      of M protein expression on translation of CAT mRNA. The results presented here
      show that M protein did not inhibit host-directed translation of CAT mRNA. On the
      contrary, this study gave the unexpected result that M protein actually
      stimulated host-directed translation under the same conditions in which it
      potently inhibited host-directed transcription. Under these conditions, the
      combined effect on host gene expression was a greater-than-20-fold inhibition.
      Furthermore, the enhancement of host translation mediated by M protein was
      genetically correlated with M protein's ability to inhibit host transcription.
      Thus, the results of this study establish that M protein does not inhibit host
      protein synthesis under the same conditions in which it potently inhibits host
      transcription and suggest that the inhibition of transcription and that of
      translation by vesicular stomatitis virus require separate viral gene products.

PMID- 8254772
TI  - Involvement of transcription factor YB-1 in human T-cell lymphotropic virus type
      I basal gene expression.
AB  - Sequences which control basal human T-cell lymphotropic virus type I (HTLV-I)
      transcription likely play an important role in initiation and maintenance of
      virus replication. We previously identified and analyzed a 45-nucleotide sequence
      (downstream regulatory element 1 [DRE 1]), +195 to +240, at the boundary of the
      R/U5 region of the long terminal repeat which is required for HTLV-I basal
      transcription. We identified a protein, p37, which specifically bound to DRE 1.
      An affinity column fraction, containing p37, stimulated HTLV-I transcription
      approximately 12-fold in vitro. We now report the identification of a cDNA clone
      (15B-7), from a Jurkat expression library, that binds specifically to the DRE 1
      regulatory sequence. Binding of the cDNA fusion protein, similarly to the results
      obtained with purified Jurkat protein, was decreased by introduction of site
      specific mutations in the DRE 1 regulatory sequence. In vitro transcription and
      translation of 15B-7 cDNA produced a fusion protein which bound specifically to
      the HTLV-I +195 to +240 oligonucleotide. The partial cDNA encodes a protein which
      is homologous to the C-terminal 196 amino acids of the 36-kDa transcription
      factor, YB-1. Cotransfection of a YB-1 expression plasmid increases HTLV-I basal
      transcription approximately 14-fold in Jurkat T lymphocytes. On the basis of the
      molecular weight, DNA-binding characteristics, and in vivo transactivation
      activity, we suggest that the previously identified DRE 1-binding protein, p37,
      is YB-1.

PMID- 8254773
TI  - Screening retroviral packaging cells for highly efficient virus production by
      using a combined selection procedure.
AB  - To facilitate the screening for clones of transfected packaging cells producing a
      high yield of recombinant retrovirus, we present a fast and simple method for the
      isolation of overexpressing cells. By this method the efficiency of virus
      production can generally be enhanced 10- to 100-fold by application of high
      selection pressure. Cell lines which exhibit titers of up to 10(8) CFU/ml were
      obtained.

PMID- 8254774
TI  - Mutations in the membrane-spanning domain of the human immunodeficiency virus
      envelope glycoprotein that affect fusion activity.
AB  - A chimeric protein consisting of the human immunodeficiency virus type 1 (HIV-1)
      envelope protein (Env) ectodomain joined to the transmembrane and cytoplasmic
      tail domains of vesicular stomatitis virus G protein lost the ability to fuse
      CD4+ HeLa cells yet was transported to the cell surface and cleaved normally.
      These results suggested some critical role of the HIV gp41 transmembrane or
      cytoplasmic domain in fusion. Subsequent mutagenic analysis of the HIV-1 Env
      transmembrane domain revealed that the sequence of amino acid residues from
      positions 696 to 707 of the transmembrane domain was important for fusion
      function but was not required for anchoring of the Env protein in the lipid
      bilayer or for transport to the cell surface. Further analysis indicated that the
      basic residues at positions 696 and 707 were critical for membrane fusion
      activity, as was the spacing between these residues. These results demonstrate
      that in addition to providing an anchoring function, the specific amino acid
      sequence in the transmembrane domain plays a crucial role in the membrane fusion
      process.

PMID- 8254775
TI  - Use of random systematic mutagenesis to generate viable human rhinovirus 14
      chimeras displaying human immunodeficiency virus type 1 V3 loop sequences.
AB  - Random systematic mutagenesis was used to generate a library of human rhinovirus
      14 chimeras that each display a segment from the V3 loop of human
      immunodeficiency virus type 1. The sequence XXIGPGRAXX, where X could be any of
      the 20 amino acids, was inserted at the neutralizing immunogenic site II of human
      rhinovirus 14 between VP2 residues 159 and 160. Twenty-five unique chimeric
      viruses were isolated, and the identity of their randomized residues was
      determined. A nonrandom amino acid distribution that may reflect structural
      requirements for viability was observed at the randomized positions. Fifteen of
      25 chimeras were neutralized by one or more of a panel of four anti-human
      immunodeficiency virus type 1 V3 loop antibody preparations, indicating that
      antigenicity had been successfully transplanted. Libraries of chimeric viruses
      produced by using the techniques described may be a source of vaccines and other
      immunotherapeutic reagents. The random systematic mutagenesis methodology
      described should be generally useful for the rapid transplantation of foreign
      sequences into viral coat and other proteins to produce libraries containing
      members with the desired properties.

PMID- 8254776
TI  - Long-term persistent infection of swine monocytes/macrophages with African swine
      fever virus.
AB  - Long-term persistent infection was established in 100% of pigs (n = 19)
      experimentally infected with African swine fever virus (ASFV). Viral DNA was
      detected in peripheral blood mononuclear leukocytes (PBML) at greater than 500
      days postinfection by a PCR assay. Infectious virus was not, however, isolated
      from the same PBML samples. In cell fractionation studies of PBML,
      monocytes/macrophages were found to harbor viral DNA during the persistent phase
      of infection. This result indicates that monocytes/macrophages are persistently
      infected with ASFV and that ASFV-swine monocyte/macrophage interactions can
      result in either lytic or persistent infection.

PMID- 8254777
TI  - Sequence conservation in field and experimental isolates of Borna disease virus.
AB  - Coding and noncoding sequences were analyzed from field and experimental isolates
      of Borna disease virus. For a 24-kDa protein, maximum divergence was 1.5% at the
      predicted amino acid level and 3.1% at the nucleotide level. For a 40-kDa
      protein, maximum divergence was 1.1% at the predicted amino acid level and 4.1%
      at the nucleotide level. The highest variability in sequence (10%) was found in a
      40-nucleotide stretch of genomic RNA between coding sequences for the 40- and 24
      kDa proteins. The degree of sequence conservation in these isolates, passaged in
      various host species in vivo and in vitro over a period of 64 years, is unusual
      for negative-strand RNA viruses.

PMID- 8254778
TI  - Sendai virus M protein binds independently to either the F or the HN glycoprotein
      in vivo.
AB  - We have analyzed the mechanism by which M protein interacts with components of
      the viral envelope during Sendai virus assembly. Using recombinant vaccinia
      viruses to selectively express combinations of Sendai virus F, HN, and M
      proteins, we have successfully reconstituted M protein-glycoprotein interaction
      in vivo and determined the molecular interactions which are necessary and
      sufficient to promote M protein-membrane binding. Our results showed that M
      protein accumulates on cellular membranes via a direct interaction with both F
      and HN proteins. Specifically, our data demonstrated that a small fraction (8 to
      16%) of M protein becomes membrane associated in the absence of Sendai virus
      glycoproteins, while > 75% becomes membrane bound in the presence of both F and
      HN proteins. Selective expression of M protein together with either F or HN
      protein showed that each viral glycoprotein is individually sufficient to promote
      efficient (56 to 73%) M protein-membrane binding. Finally, we observed that M
      protein associates with cellular membranes in a time-dependent manner, implying a
      need for either maturation or transport before binding to glycoproteins.

PMID- 8254779
TI  - Analysis of astrovirus serotype 1 RNA, identification of the viral RNA-dependent
      RNA polymerase motif, and expression of a viral structural protein.
AB  - We report the results from sequence analysis and expression studies of the
      gastroenteritis agent astrovirus serotype 1. We have cloned and sequenced 5,944
      nucleotides (nt) of the estimated 7.2-kb RNA genome and have identified three
      open reading frames (ORFs). ORF-3, at the 3' end, is 2,361 nt in length and is
      fully encoded in both the genomic and subgenomic viral RNAs. Expression of ORF-3
      in vitro yields an 87-kDa protein that is immunoprecipitated with a monoclonal
      antibody specific for viral capsids. This protein comigrates with an authentic 87
      kDa astrovirus protein immunoprecipitated from infected cells, indicating that
      this region encodes a viral structural protein. The adjacent upstream ORF (ORF-2)
      is 1,557 nt in length and contains a viral RNA-dependent RNA polymerase motif.
      The viral RNA-dependent RNA polymerase motifs from four astrovirus serotypes are
      compared. Partial sequence (2,018 nt) of the most 5' ORF (ORF-1) reveals a 3C
      like serine protease motif. The ORF-1 sequence is incomplete. These results
      indicate that the astrovirus genome is organized with nonstructural proteins
      encoded at the 5' end and structural proteins at the 3' end. ORF-2 has no start
      methionine and is in the -1 frame compared with ORF-1. We present sequence
      evidence for a ribosomal frameshift mechanism for expression of the viral
      polymerase.

PMID- 8254780
TI  - Homologs of vascular endothelial growth factor are encoded by the poxvirus orf
      virus.
AB  - A gene encoding a polypeptide with homology to mammalian vascular endothelial
      growth factors (VEGFs) has been discovered in the genome of orf virus (OV), a
      parapoxvirus that affects sheep and goats and, occasionally, humans. The gene is
      transcribed abundantly early in infection and is found immediately outside the
      inverted terminal repeat at the right end of the genome. In the NZ2 strain of OV
      (OV NZ2), the gene encodes a polypeptide with a molecular size of 14.7 kDa, while
      in another strain, OV NZ7, there is a variant gene that encodes a polypeptide of
      16 kDa. The OV NZ2 and OV NZ7 polypeptides show 22 to 27% and 16 to 23% identity,
      respectively, to the mammalian VEGFs. The viral polypeptides are only 41.1%
      identical to each other, and there is little homology between the two genes at
      the nucleotide level. Another unusual feature of these genes is their G+C
      content, particularly that of OV NZ7. In a genome that is otherwise 63% G+C, the
      OV NZ2 gene is 57.2% G+C and the OV NZ7 gene is 39.7% G+C. The OV NZ2 gene, but
      not the OV NZ7 gene, is homologous to the mammalian VEGF genes at the DNA level,
      suggesting that the gene has been acquired from a mammalian host and is
      undergoing genetic drift. The lesions induced in sheep and humans after infection
      with OV show extensive dermal vascular endothelial proliferation and dilatation,
      and it is likely that this is a direct effect of the expression of the VEGF-like
      gene.

PMID- 8254781
TI  - Temporal patterns of human immunodeficiency virus type 1 transcripts in human
      fetal astrocytes.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection of the developing central
      nervous system results in a dementing process in children, termed HIV-1
      associated encephalopathy. Infection of astroglial elements of the pediatric
      nervous system has been demonstrated and suggests that direct infection of some
      astrocytes may contribute to the neurologic deficit. In this model, HIV-1
      establishes a persistent state of infection in astrocytes, which can be
      reactivated by the cytokines tumor necrosis factor alpha (TNF-alpha) and
      interleukin 1 beta (IL-1 beta). To better understand the natural history of viral
      persistence in astroglial cells, we characterized infection at the
      transcriptional level. The most abundant viral transcript during the
      establishment of persistence was the subgenomic multiply spliced 2-kb message,
      similar to mononuclear cell models of HIV-1 latency. Following reactivation with
      TNF-alpha or IL-1 beta the multiply spliced 2-kb message remained the most
      abundant viral transcript, in contrast to infected mononuclear cells in which
      reactivation leads to the reemergence of the 9- and 4-kb transcripts. Further
      characterization of the persistent 2-kb transcript by PCR amplification of in
      vitro-synthesized viral cDNA showed that, in the absence of cytokine stimulation,
      the most abundant multiply spliced transcripts were the Nef- and Rev-specific
      messages. However, following cytokine stimulation, double- and triple-spliced Tat
      , Rev-, and Nef-specific messages could be identified. Immunohistochemical
      staining demonstrated that, during viral persistence, astrocytes expressed Nef
      protein but few or no viral structural proteins. These results demonstrate that
      viral persistence in astrocytes at the transcriptional level is fundamentally
      different from that seen in mononuclear cells and could account for the virtual
      absence of astroglial expression of viral structural antigens in vivo.

PMID- 8254782
TI  - Management of atherosclerotic renal artery disease in younger patients.
AB  - From 1970 to 1990, 57 patients 50 years old or younger were treated for
      hypertension caused by atherosclerotic renal artery disease. Predisposing factors
      for atherosclerosis included smoking in 43 cases, hyperlipidemia in 15, diabetes
      in 8 and hyperuricemia in 8. Of the patients 47 had a family history of
      atherosclerotic vascular disease or a significant related disorder. Evidence of
      generalized atherosclerosis was present in 55 patients. Atherosclerotic renal
      artery disease was present unilaterally in 16 cases, bilaterally in 39 and in a
      solitary kidney in 2. Of the patients 34 were treated surgically, 20 medically
      and 2 by percutaneous angioplasty. Surgically treated patients experienced
      significant postoperative improvement in blood pressure (p = 0.001) and renal
      function (p = 0.05). Medically treated patients experienced significant
      improvement in blood pressure (p = 0.03) but renal function deteriorated. Younger
      patients with atherosclerotic renal artery disease suffer from a more severe and
      accelerated form of atherosclerosis than older patients. Although blood pressure
      control can be achieved with medical treatment, surgical revascularization offers
      the best opportunity for stabilization or improvement of renal function.

PMID- 8254783
TI  - Ciprofloxacin as prophylaxis for urinary tract infection: prospective,
      randomized, cross-over, placebo controlled study in patients with spinal cord
      lesion.
AB  - To evaluate the efficacy of low-dose long-term treatment with ciprofloxacin in
      the prevention of recurrent urinary tract infections in patients with spinal cord
      lesions and neurogenic bladder dysfunction, a prospective, randomized, cross
      over, placebo-controlled study was performed. The study period was 12 months
      long, including 6 months of treatment with 100 mg. ciprofloxacin at night and 6
      months of placebo treatment. The study was completed by 18 men and 3 women,
      median age 38 years (range 19 to 73 years). Within the last 12 months before
      inclusion into the study, the patients had between 3 and 14 urinary tract
      infections (mean 5.8) treated with antimicrobial agents. The number of urinary
      tract infections treated with antimicrobial agents during 6 months of
      ciprofloxacin prophylaxis was 5 and during the 6 months of placebo treatment it
      was 59 (p < 0.00005) [corrected]. Fecal specimens showed supercolonization with
      ciprofloxacin resistant bacteria (Acinetobacter calcoaceticus) in 1 instance. No
      severe side effects were observed. Ciprofloxacin at a dose of 100 mg. at night
      was efficacious in preventing urinary tract infections during 6 months in
      patients with spinal cord lesions and neurogenic bladder dysfunction. After the
      controlled study 10 of the 21 patients used ciprofloxacin as prophylaxis for up
      to 39 months with a marked reduction in the pre-study infection frequency. In 1
      patient ciprofloxacin resistant Escherichia coli was subsequently found in the
      feces.

PMID- 8254784
TI  - Acute hemostasis during laparoscopic procedures: method for intraoperative
      application of hemostatic material.

PMID- 8254785
TI  - Endocrine profiles and semen quality of spinal cord injured men.
AB  - We characterized endocrine profiles and semen quality in spinal cord injury
      subjects using noninjured normal and infertile subjects as controls. Compared to
      normal controls, spinal cord injury subjects had lower serum levels of
      luteinizing hormone and follicle-stimulating hormone. Subjects with spinal cord
      injuries between the T8 and T10 levels had a higher incidence of hormone outliers
      compared to subjects with injuries at other levels. Sperm motility and per cent
      normal sperm morphology were lower in spinal cord injury subjects compared to
      normal controls but not to infertile control subjects. Spinal cord injury
      subjects with elevated follicle-stimulating hormone levels were azoospermic. We
      conclude that endocrine abnormalities are likely to accompany spinal cord injury
      but may not be the sole mechanism contributing to impairments in semen quality.

PMID- 8254786
TI  - Spontaneous rupture of adrenal pheochromocytoma: a case report.
AB  - We report a case of retroperitoneal hemorrhage due to spontaneous rupture of a
      right adrenal pheochromocytoma, presenting as an acute abdominal emergency with
      symptoms of peripheral vasoconstriction. An elective operation was successfully
      performed on day 7 after sufficient volume replacement with continuous
      administration of an alpha and beta-adrenergic blocking agent.

PMID- 8254787
TI  - Laparoscopic treatment of a stone-filled, caliceal diverticulum: a definitive,
      minimally invasive therapeutic option.
AB  - We describe the laparoscopic treatment of a symptomatic, stone-filled caliceal
      diverticulum in a patient who would have otherwise required open surgical
      excision of the diverticulum. Laparoscopic management was chosen as an
      alternative to an open operation in this patient because the anterior location of
      the diverticulum precluded treatment with percutaneous nephrolithotomy, while the
      stone burden and stenotic orifice precluded management with extracorporeal shock
      wave lithotripsy. The patient had no morbidity, returned to the preoperative
      activity level by 2 weeks and remains asymptomatic. The options for managing
      caliceal diverticula are discussed.

PMID- 8254788
TI  - Gas in hepatic veins: a rare and critical presentation of emphysematous
      pyelonephritis.
AB  - Although emphysematous pyelonephritis has been recognized for more than a hundred
      years, the actual etiology is still unknown. Glucose fermentation has been
      implicated as a mechanism of gas formation. We report a case of emphysematous
      pyelonephritis in which real-time ultrasonography demonstrated intravascular gas
      bubbles originating in the involved kidney, and passing into the inferior vena
      cava and hepatic veins. Gas from the affected kidney was analyzed by
      chromatography; the result showed hydrogen 10.5%, carbon dioxide 39%, nitrogen
      49.6% and oxygen 0.8%. The clinical presentation and the results of gas analysis
      implicate a critical condition that bacteria proliferated rapidly by mixed acid
      fermentation of glucose. Additionally, the finding of gas production and
      transportation could explain the previous hypothesis of gas transport. In this
      critical situation immediate drainage with medical intervention is indicated to
      treat this life threatening condition.

PMID- 8254789
TI  - Xanthogranulomatous pyelonephritis in renal allografts: report of 2 cases.
AB  - We report 2 cases of xanthogranulomatous pyelonephritis that occurred in renal
      transplant recipients. Both cases were successfully treated with antibiotics. The
      traditional treatment of choice has been nephrectomy. No graft was lost as a
      result of xanthogranulomatous pyelonephritis and no nephrectomy was required in
      either patient. The course of these 2 patients is discussed and literature on
      this disease is reviewed.

PMID- 8254790
TI  - Acquired cystic disease and renal adenocarcinoma following renal transplantation.
AB  - Acquired renal cystic disease has been associated with the development of renal
      cell carcinoma in patients on chronic dialysis. The disease has been documented
      to regress in the native kidney after successful renal transplantation. We report
      4 cases of renal cell carcinoma occurring in the native kidney 3 to 8 years after
      successful renal transplantation. Of these patients 3 also had acquired cystic
      disease of the native kidney. These 3 cases suggest that the malignant potential
      associated with acquired renal cystic disease may not be reduced significantly by
      renal transplantation and that periodic imaging of the native kidney is advisable
      after transplantation, particularly when the disease is present before
      transplantation.

PMID- 8254791
TI  - Complications of intracavitary bacillus Calmette-Guerin after percutaneous
      resection of upper tract transitional cell carcinoma.
AB  - Percutaneous resection and intracavitary instillation of bacillus Calmette-Guerin
      (BCG) is currently being used in treatment protocols in select patients in whom
      the standard nephroureterectomy for upper tract transitional cell carcinoma is
      undesirable. However, the complications of BCG in these patients are not well
      defined. Among 16 patients treated in this manner 4 (25%) had asymptomatic
      granulomatous involvement of the renal pelvis discovered during regular followup
      nephroscopy and biopsy: 2 had recurrent carcinoma at discovery, whereas the other
      2 remain free of disease. The significance and therapeutic consequences of BCG
      granulomatosis are unknown. Continued followup is necessary to identify any
      complications of BCG therapy.

PMID- 8254792
TI  - Metastatic renal cell carcinoma to the right cardiac ventricle without contiguous
      vena caval involvement.
AB  - We report an unusual metastatic renal cell carcinoma in the right cardiac
      ventricle in a 53-year-old man who presented with increasing dyspnea. Diagnostic
      evaluation revealed a left renal tumor without contiguous extension into the
      inferior vena cava and a right ventricular mass. To our knowledge this is only
      the second reported case of metastatic renal cell carcinoma to the right cardiac
      ventricle diagnosed ante mortem. We discuss the case and review the literature.

PMID- 8254793
TI  - Laparoscopic retroperitoneal renal cystectomy.
AB  - Laparoscopic manipulation of retroperitoneal organs is usually performed by the
      transperitoneal approach primarily because of the ease of access by way of the
      pneumoperitoneum. However, difficulty in adequately accessing structures that are
      surrounded by bowel, liver, spleen or postoperative adhesions makes this approach
      suboptimal in certain cases. We describe the use of the retroperitoneal
      laparoscopic approach to the upper pole of a kidney for marsupialization of a
      symptomatic, recurrent, complex renal cyst. An algorithm for current management
      of symptomatic renal cysts is discussed.

PMID- 8254794
TI  - Retroperitoneal hemorrhage from a ruptured renal artery aneurysm with spontaneous
      resolution.
AB  - Rupture of a renal artery aneurysm is an acute surgical event with a high
      associated mortality rate. We report an unusual case of acute retroperitoneal
      hemorrhage from a ruptured renal artery aneurysm that resolved spontaneously with
      resultant pseudoaneurysm formation. Elective surgical management was performed
      with a simplified technique involving ligation of the neck of the renal artery
      aneurysm.

PMID- 8254795
TI  - Ureteritis cystica with 17-year followup.
AB  - Ureteritis cystica is a rare disease that must be considered in the differential
      diagnosis of ureteral and renal pelvic filling defects. The characteristic
      radiographic findings often regress spontaneously when the process instigating
      the inflammation is eradicated. However, in our patient radiological findings
      remained unchanged during a 17-year period in the absence of malignancy or
      infection. Although it sometimes coexists with cancer, we believe that ureteritis
      cystica is usually benign and indolent.

PMID- 8254796
TI  - Extracorporeal shock wave lithotripsy induced stimulation of the obturator nerve.
AB  - Extracorporeal shock wave lithotripsy to a left lower third ureteral calculus,
      1.4 x 0.9 cm. large, using an unmodified Dornier HM3* lithotriptor with the
      patient in the sitting position produced thigh adductor movement with each shock.
      The procedure was terminated. Extracorporeal shock wave lithotripsy was performed
      uneventfully 1 week later using a Medstone STS lithotriptor with the patient in
      the supine position. We believe that the sitting position caused increased intra
      abdominal pressure in the pelvis resulting in apposition of the ureteral segment
      containing the calculus to the obturator nerve, which was included either in the
      second focal point or in the extended shock path of the Dornier HM3 unit.

PMID- 8254797
TI  - Special considerations in the technique of laparoscopic ureterolithotomy.
AB  - Laparoscopic ureterolithotomy was performed in 2 men, accompanied in 1 by
      unroofing of a complex renal cyst. This new technique is indicated as an
      alternative to open lithotomy when more conventional minimally invasive measures
      have failed and in patients in whom laparoscopy is being performed for another
      indication. Modifications in technique are necessary depending on the location of
      the stone. Laparoscopic ureterolithotomy should not be performed unless a guide
      wire or catheter can be placed past the stone preoperatively. The technique is
      described in detail.

PMID- 8254798
TI  - Ureteropelvic junction obstruction secondary to periureteral lipoma.
AB  - We report a unique case of extrinsic ureteral obstruction secondary to a
      periureteral lipoma discovered during pyeloplasty for an apparent ureteropelvic
      junction obstruction. We discuss the importance of preoperative recognition of
      rare extrinsic causes of ureteropelvic junction obstruction.

PMID- 8254799
TI  - Hemorrhagic cystitis associated with herpes simplex virus.
AB  - A 45-year-old man presented with hemorrhagic cystitis and was found to have
      herpes simplex infection of the bladder by biopsy, immunohistochemistry and in
      situ hybridization. The patient had no clinical evidence of immunosuppression or
      disseminated infection. Although viral etiologies of hemorrhagic cystitis are
      recognized, to our knowledge only 4 cases of hemorrhagic cystitis due to herpes
      simplex virus have been reported.

PMID- 8254800
TI  - Malignant fibrous histiocytoma of the bladder with focal rhabdoid tumor
      differentiation.
AB  - A case of primary malignant fibrous histiocytoma of the bladder is presented.
      This tumor involving the bladder is rare and the unusual histological features in
      the present case caused significant delay in accurate diagnosis. Since early
      diagnosis and aggressive surgical resection are essential to the effective
      treatment of this neoplasm, physicians should continually bear in mind the
      possibility of this malignant tumor whenever the pathological diagnosis is
      inconclusive.

PMID- 8254801
TI  - Benign testicular tumor associated with Klinefelter's syndrome.
AB  - Testicular tumors associated with Klinefelter's syndrome are rare. We report a
      benign testicular epidermal cyst that was diagnosed in a patient with
      Klinefelter's syndrome. The association between testicular tumors and
      Klinefelter's syndrome, and management of a testicular epidermal cyst are
      discussed.

PMID- 8254802
TI  - Segmental infarction of the testicle: atypical presentation of a testicular mass.
AB  - Segmental infarction of the testis represents a rare entity. To our knowledge 11
      cases have been reported in the literature. We report 4 additional cases of
      segmental testicular infarction masquerading as testis tumors. Inability to
      distinguish these benign lesions from malignant testis tumors resulted in
      orchiectomy in all 4 cases.

PMID- 8254803
TI  - The content of urokinase-type plasminogen activator and tumor recurrence in
      superficial bladder cancer.
AB  - The contents of urokinase-type plasminogen activator were estimated in
      superficial bladder cancer from 42 patients undergoing transurethral resection
      for the first time. Tumor recurred in 11 of 16 patients (68.8%) with high
      urokinase-type plasminogen activator content (8 ng. urokinase-type plasminogen
      activator per mg. protein and more) and in 12 of 26 (46.2%) with low urokinase
      type plasminogen activator content. In the high content group 8 patients (50%)
      had disease progression compared to 2 (7.7%) in the low content group (p < 0.01).
      The progression rates in the high urokinase-type plasminogen activator group with
      stage pTa disease or tumors more than 1 cm. large were significantly higher than
      those in the low urokinase-type plasminogen activator group (p < 0.05). The
      recurrence and progression rates in the high content group with stage pT1, grades
      2 and 3, single and multiple tumors, and tumors less than 1 cm. large were higher
      than those in the low content group. The progression-free survival rate in the
      high content group was significantly lower than that in the low content group (p
      < 0.005). In conclusion, urokinase-type plasminogen activator content may be a
      useful marker to predict recurrence and progression of superficial bladder
      cancer.

PMID- 8254804
TI  - Malignant melanoma of the scrotum: report of 2 cases.
AB  - Primary melanoma of the scrotum is a rare entity, with only 4 cases reported
      previously. Of about 2,000 patients with malignant melanoma treated in the last
      15 years at our hospital only 2 had primary melanoma of the scrotum. The
      treatment and outcome of these patients are presented.

PMID- 8254805
TI  - Femoral neuropathy following major pelvic surgery: etiology and prevention.
AB  - We report a case of femoral neuropathy occurring after radical cystoprostatectomy
      and continent urinary diversion. Urologists who perform major pelvic surgery need
      to be familiar with this complication to prevent its occurrence.

PMID- 8254806
TI  - Wilms tumor: the problem of diagnostic accuracy in children undergoing
      preoperative chemotherapy without histological tumor verification.
AB  - From 1989 to 1992, 9 consecutive children with a tentative diagnosis of Wilms
      tumor underwent therapy planned according to the International Society of
      Pediatric Oncology (SIOP)-9 Wilms tumor protocol, including preoperative
      chemotherapy. Because tumor biopsy is not recommended in this SIOP-9 protocol due
      to a possible tumor spread from open or needle biopsy, diagnostic accuracy is
      mandatory. We present our problems in diagnostic accuracy resulting in withdrawal
      of 2 children from preoperative chemotherapy, understaging the tumor in 2 and
      missing exact tumor histology due to complete tumor necrosis in 2. In addition,
      preoperative chemotherapy was applied in 1 child who later was found to have
      renal cell carcinoma. Although the SIOP-9 protocol of Wilms tumor treatment may
      be effective with regard to reducing the intensity of therapy, staging problems
      may be a major drawback in this therapeutic strategy based on preoperative
      chemotherapy.

PMID- 8254807
TI  - Urological aspects of intra-abdominal desmoplastic small round cell tumor of
      childhood: a preliminary report.
AB  - To our knowledge intra-abdominal desmoplastic round cell tumor has not previously
      been described in the pediatric urological literature. This lesion has only
      recently been recognized as a clinicopathological entity with predilection for
      adolescent boys. We report on 2 patients who presented with urological symptoms
      and a large abdominal or pelvic tumor that was biopsied at exploratory
      laparotomy. Complete surgical excision was impossible in both patients, who
      subsequently underwent multiagent chemotherapy. Histological and
      immunohistochemical staining are distinctive in this condition. The tumor is
      associated with a poor prognosis, despite multidisciplinary, multimodal therapy.

PMID- 8254808
TI  - Lower urinary tract dysfunction in children with benign sacrococcygeal teratoma.
AB  - We evaluated 8 girls and 3 boys with benign sacrococcygeal teratoma for lower
      urinary tract dysfunction. All children underwent ultrasonography of the urinary
      tract, voiding cystourethrography and at least 2 standard urodynamic evaluations.
      Mean patient age at first urodynamic study was 59 months (range 1 to 136). Nine
      of the 11 children had abnormal studies, including detrusor instability and
      associated pelvic floor overactivity during micturition in 2, an anatomical
      infravesical obstruction in 2 and neurogenic bladder-sphincter dysfunction in 5
      (2 detrusor hyperreflexia with sphincter dyssynergia, 2 hyporeflexic bladder
      sphincter function and 1 detrusor hyporeflexia with normal sphincter function).
      Although the major cause of neurogenic lower urinary tract dysfunction seems to
      be related to surgical trauma of the pelvic plexus and sacral nerves, we observed
      tethered spinal cord as a primary cause in 2 patients. The incidence of voiding
      dysfunction in children with sacrococcygeal teratoma is high and is usually
      neurogenic in origin.

PMID- 8254809
TI  - A prospective evaluation of leak point pressure, bladder compliance and clinical
      status in myelodysplasia patients with tethered spinal cords.
AB  - We evaluated prospectively 26 patients with myelodysplasia and a tethered spinal
      cord to determine whether surgical release of the tethered cord positively
      influenced leak point pressure, bladder compliance, upper tract status and/or
      clinical management. Urodynamics were performed immediately before and after the
      neurosurgical procedure, and at 3 and 6 months postoperatively. Mean patient age
      was 7.8 years (range 2 days to 34 years) and median interval from onset of
      symptoms to surgery was 60 days (range 2 days to 4 years). Patient presentation
      included a combination of orthopedic, neurological and urological symptoms. Of 26
      patients 9 (35%) had new hydronephrosis, urinary tract infections or urinary
      incontinence. Leak point pressure and bladder compliance did not change
      significantly by 6 months postoperatively. Of the 4 patients who presented with
      hydronephrosis 1 worsened in status, 2 stabilized and 1 improved. Clinical status
      was unchanged in 16 patients, improved in 4 and worsened in 6. There was no
      significant relationship between patient age and urodynamic or clinical outcome.
      Among patients followed for at least 6 months radiographic and clinical
      improvement occurred in 25% and 15%, respectively. Urodynamic improvements were
      transient. Surgical release of a tethered cord improved the urological status in
      less than a quarter of the patients in this series.

PMID- 8254810
TI  - Iliac osteotomy: a model to compare the options in bladder and cloacal exstrophy
      reconstruction.
AB  - Bladder exstrophy and cloacal exstrophy present challenging reconstructive
      problems. Traditionally, bilateral posterior iliac osteotomy has been performed
      in the majority of patients undergoing primary closure for these abnormalities.
      Recently, 2 anterior osteotomy approaches have been proposed: 1) incision of the
      ilium transversely above the acetabulum (transverse osteotomy) and 2) incision of
      the superior ramus of the pubis (superior ramus osteotomy). We devised a new
      anterior mid-iliac diagonal osteotomy that provides a more functional pelvic
      closure. To provide a fair comparison of the procedures we developed a pelvic
      exstrophy model based on data from a 3-dimensional computerized tomogram of a 3
      year-old patient with classical bladder exstrophy. The different osteotomies were
      then performed on the model and the results were compared. Our new anterior mid
      iliac diagonal osteotomy correction allowed the best surgical approach, provided
      the best correction of the flattened ilia bony deformities, was performed in the
      thinnest area of marrow bone and resulted in the best pelvic symmetry.

PMID- 8254811
TI  - The importance of urinary tract infection in the evaluation of the incontinent
      child.
AB  - Diurnal incontinence secondary to dysfunctional voiding is a problem that is
      commonly encountered by the pediatric urologist. We have observed that reflux is
      more common in these children and hypothesized that urinary tract infection would
      influence the rate of reflux as well as the rate of significant urinary tract
      abnormalities, such as renal scarring. We prospectively evaluated 308 incontinent
      children with a voiding cystourethrogram and upper tract studies. Of these
      patients 162 (53%) had had previous culture proved urinary tract infection, while
      146 (47%) had no history of infection. A total of 90 patients (29%) had an
      abnormal voiding cystourethrogram, which demonstrated reflux in all but 1. Among
      the patients with a history of urinary tract infection reflux was found in 34%
      compared to 23.3% in those with no history of urinary tract infection (p = 0.82).
      Five patients had significant cortical scarring, of whom 4 had grade III or
      greater reflux along with urinary tract infection. We conclude that urinary tract
      infection is not helpful in determining which patients with dysfunctional voiding
      will exhibit vesicoureteral reflux but it is important in detecting significant
      upper tract abnormalities, such as renal scarring. We discuss appropriate
      evaluation in children who present with incontinence secondary to dysfunctional
      voiding with or without urinary tract infections.

PMID- 8254812
TI  - Changing concepts of hypospadias curvature lead to more onlay island flap
      procedures.
AB  - From 1987 through 1992, 1,109 primary hypospadias operations were performed at
      our hospital, of which 374 (33%) were onlay island flap procedures. In contrast,
      from 1982 to 1987 only 66 of 657 primary hypospadias repairs (10%) were onlay
      island flaps. The increase in this type of repair stems from the observation that
      in most cases of hypospadias the urethral plate is not the cause of penile
      curvature. Intraoperative artificial erection after skin take down revealed that
      only 50 of the 374 patients (13%) still had a significant bend. After experience
      demonstrated that the residual bend was not due to a fibrous urethral plate, but
      rather to a generally mild (20 to 30 degree) corporeal disproportion, correction
      was achieved by dorsal tunica albuginea plications. We conclude that better
      healing of the onlay flap to spongiosum supported urethral plate may account for
      the lower fistula rate (6%) observed with the onlay island flap hypospadias
      repair, and even in severe cases of hypospadias the urethral plate is usually
      healthy and it does not require division to produce a straight penis.

PMID- 8254813
TI  - Experimental hypercholesterolemia in rabbits induces cavernosal atherosclerosis
      with endothelial and smooth muscle cell dysfunction.
AB  - Hypercholesterolemia and other vascular risk factors for atherosclerosis are
      commonly associated with impotence. To characterize cavernosal smooth muscle
      reactivity in hypercholesterolemia, we performed isometric tension studies (with
      norepinephrine, acetylcholine, papaverine and electrical field stimulation) on
      isolated strips of corpus cavernosum from rabbits fed a 1% cholesterol diet. To
      assess the impact of cholesterol reduction, a group of rabbits was fed a
      cholesterol diet for 4 weeks and was then returned to a normal diet for 4 weeks
      before testing. Potential structure-function relationships were delineated by
      ultrastructural evaluation with transmission electron microscopy (TEM). All forms
      of cavernosal relaxation, including papaverine relaxation, were impaired with
      hypercholesterolemia, and norepinephrine contraction was augmented. In addition,
      ultrastructural evidence of an early atherosclerotic process in the cavernosal
      sinusoids was detected. Importantly, reduction of elevated serum cholesterol
      normalized cavernosal relaxation, including that of papaverine, and decreased the
      sensitivity to norepinephrine, thereby suggesting that cavernosal smooth muscle
      dysfunction in hypercholesterolemia is reversible.

PMID- 8254814
TI  - The in vitro cytotoxicity of urine from patients with interstitial cystitis.
AB  - Urine from patients with interstitial cystitis has been reported to be more
      cytotoxic than urine from healthy subjects when tested in vitro against cells
      from a normal urothelial cell line. The purpose of the present study was to
      develop a method to measure urinary cytotoxicity and so make it possible to
      estimate the toxicity of urine from interstitial cystitis patients. The study
      included 10 women with interstitial cystitis and 10 healthy controls. Urine
      specimens were obtained from both groups and urine cytotoxicity was measured by a
      modified 51Cr-release assay: A range of urine dilutions was added to suspensions
      of target cells with intracellular bound 51Cr, and cellular death was recorded by
      measuring the 51Cr-release from the target cells. The transitional cell bladder
      cell lines T24 and Hu609 and the erythroleukemia K562 cell line were used as
      target cells. There was no difference in urine cytotoxicity between interstitial
      cystitis patients and healthy controls. Urine cytotoxicity was increased by
      dilution in both groups.

PMID- 8254815
TI  - Angiotensin II receptor subtypes in the human renal cortex and renal cell
      carcinoma.
AB  - Selective antagonists were used to determine the presence of angiotensin II (Ang
      II) receptor subtypes (AT1 and AT2) in normal human renal cortex and renal cell
      carcinoma. Normal and tumor tissues were obtained from fresh radical nephrectomy
      specimens in 7 patients. All patients had a patent renal artery, and the mean
      preoperative serum creatinine level was 1.1 mg./dl. Tissues were snap frozen and
      sectioned (14 microns.) for in vitro autoradiography, then incubated in 125I-Ang
      II (0.3 nM.), with or without unlabeled Ang II or subtype selective antagonists
      (1 nM. to 1 microM.), rinsed, air dried and apposed to SB-5 X-ray film for 3 to
      21 days. In normal renal tissue, low densities of diffuse 125I-Ang II binding
      sites were observed in cortical areas containing tubules. Higher densities of
      binding sites occurred over glomeruli and large cortical vessels. Specific
      binding ranged between 60 and 90% depending on the area as determined by
      displacement with excess unlabeled Ang II. Specific binding in large cortical
      vessels was displaced by the two AT2 selective antagonists PD123177 (1 microM.)
      or CGP 42112A (0.01 microM.), whereas these antagonists were less effective
      competitors for 125I-Ang II binding in glomeruli. In contrast, the AT1 selective
      antagonists, DuP 753 and L-158,809 (0.1 and .01 microM., respectively), were
      potent competitors for glomerular, but not extraglomerular, cortical vessel
      binding. In the normal cortical tubulointerstitium, both AT1 and AT2 antagonists
      caused partial displacement of specific binding (55 +/- 12% AT1, 39 +/- 12% AT2).
      Low density 125I-Ang II binding was present in all tumors. Specific binding
      averaged 59 +/- 10% as defined by displacement with unlabeled Ang II (1 microM.).
      As in the normal tubulointerstitial area, each of the selective antagonists
      produced partial displacement of the specific binding (60 +/- 12% AT1, 31 +/- 8%
      AT2). In conclusion, AT1 receptors predominate in glomeruli, while AT2 binding
      sites predominate in large preglomerular vessels of the human renal cortex. In
      the normal tubulointerstitium and renal cell carcinoma, a 60%/40% mixture of AT1
      to AT2 receptors exists. These findings provide a pharmacologic framework for the
      differential effects of Ang II receptor-mediated function in the human kidney.

PMID- 8254816
TI  - Megadose vitamins in bladder cancer: a double-blind clinical trial.
AB  - Epidemiological and laboratory studies suggest that vitamin supplements may be
      helpful in the prevention of some cancers but clinical trials to date have failed
      to demonstrate protection with naturally occurring vitamins. Without
      substantiation of the highly touted benefits of vitamins, few physicians who care
      for cancer patients have recommended their use. A total of 65 patients with
      biopsy confirmed transitional cell carcinoma of the bladder enrolled in a
      randomized comparison of intravesical bacillus Calmette-Guerin (BCG) with or
      without percutaneous administration was also randomized by closed envelope to
      therapy with multiple vitamins in the recommended daily allowance (RDA) versus
      RDA multivitamins plus 40,000 units vitamin A, 100 mg. vitamin B6, 2,000 mg.
      vitamin C, 400 units vitamin E and 90 mg. zinc. The addition of percutaneous BCG
      did not significantly lessen tumor recurrence but recurrence after 10 months was
      markedly reduced in patients receiving megadose vitamins. The 5-year estimates of
      tumor recurrence are 91% in the RDA arm and 41% in the megadose arm (p = 0.0014,
      Mantel-Cox). Overall recurrence was 24 of 30 patients (80%) in the RDA arm and 14
      of 35 (40%) in the high dose arm (p = 0.0011, 2-tailed Fisher's exact test).
      Megadose vitamins A, B6, C and E plus zinc decrease bladder tumor recurrence in
      patients receiving BCG immunotherapy. Further research will be required to
      identify which ingredient(s) provide this protection.

PMID- 8254818
TI  - Antitumoral effects of liarozole in androgen-dependent and independent R3327
      Dunning prostate adenocarcinomas.
AB  - We examined the in vivo antitumoral effects of liarozole against androgen
      dependent and independent Dunning rat prostatic tumors. Liarozole, applied as a
      dietary admixture, at a dose of 120 mg./100 gm. food, equivalent to 100 mg./kg.
      per day, inhibited the growth of the slow growing, well-differentiated, androgen
      dependent Dunning-H tumor (median tumor volume decrease of 60%). At the same dose
      it also significantly reduced the growth of the androgen-independent, moderately
      differentiated PIF-1 (-60%) and androgen-independent, anaplastic AT-6 tumors (
      73%). The growth of AT-6 sq tumor showing squamous metaplasia was unaffected by
      liarozole. When administered by oral gavage, liarozole at 40 (-82%) mg./kg. twice
      a day was as effective as castration (-92%) in reducing the androgen-dependent,
      poorly differentiated Dunning R3327-G tumor. Liarozole, administered by gavage,
      twice a day, also significantly reduced median tumor volume in the androgen
      independent, AT-6 sq (-90% at 60 mg./kg., twice a day). This difference between
      liarozole administration by gavage and food admixture will have to be taken into
      account in further experimental studies. Inhibition of the growth of several
      androgen-dependent and, chiefly, androgen-independent Dunning prostate carcinoma
      sublines that differ widely in their histological degree of differentiation and
      growth rate suggests that liarozole may be a suitable agent for evaluation in
      second line treatment of hormone refractory prostate carcinoma in patients who
      relapse after androgen ablation.

PMID- 8254817
TI  - Vaginal immunization of monkeys against urinary tract infection with a multi
      strain vaccine.
AB  - Cynomolgus monkeys were treated with a vaccine containing 10 heat-killed
      uropathogenic bacteria including 6 Escherichia coli strains. The multi-strain
      vaccine was administered either as a vaginal surface immunogen or
      intramuscularly. Following an induced E. coli cystitis, bladder infections were
      significantly reduced compared with controls at 1 and 2 weeks (intramuscular
      route) or 1 week (vaginal route) after UTI. This vaccine has been shown to be
      efficacious against cystitis in humans when given parenterally and has now proved
      efficacious in nonhuman primates by the vaginal mucosal route.

PMID- 8254819
TI  - Influence of growth factors on in vitro invasiveness and type IV collagenolysis
      of human renal cell carcinoma cells.
AB  - We investigated the influence of epidermal growth factor (EGF) and transforming
      growth factor (TGF)-beta 1 on the in vitro invasion and type IV collagenolytic
      activity of two new cell lines of renal cell carcinoma (SRCC-1P and SRCC-1M).
      When cells were treated with EGF or with TGF-beta 1, EGF increased the number of
      cells penetrating through the reconstituted basement membrane in SRCC-1P. In
      contrast, TGF-beta 1 suppressed the number of cells penetrating through the
      membrane in SRCC-1M. In accordance with the invasiveness, EGF enhanced the
      activity of type IV collagenolysis in SRCC-1P, and TGF-beta 1 suppressed it in
      SRCC-1M. The growth factors did not affect DNA synthesis of the cells as
      evaluated by 3H-thymidine incorporation. These results suggest that EGF and TGF
      beta 1 can influence the in vitro invasive process of renal cell carcinoma cells
      through their actions on proteolysis such as type IV collagenolysis.

PMID- 8254820
TI  - An electromyographic study on the urethral rhabdosphincter in normal and
      chronically rhizotomized cats: analysis of electrical potentials evoked by
      sympathetic nerve stimulation.
AB  - To investigate functional aspects of sympathetic nerve influence on the urethral
      rhabdosphincter, we examined electrical potentials of the male feline
      rhabdosphincter evoked by hypogastric nerve (HGN) stimulation using
      electromyography. Hypogastric nerve stimulation (1 Hz) elicited electrical
      potentials of the rhabdosphincter in both normal and chronically rhizotomized
      cats. In normal cats, the evoked potentials were not affected by transection of
      the bilateral pudendal nerves. The amplitudes of the evoked potentials were
      significantly larger in rhizotomized cats (p < 0.001), while the threshold
      stimuli and latency periods were not. These evoked potentials were prazosin- and
      atropine-resistant, but were abolished by hexamethonium and pancuronium in both
      groups. In normal cats, high frequency stimulation (10 to 20 Hz) of the HGN
      increased the activity of the rhabdosphincter when the bladder was empty, but not
      when the bladder was full enough to trigger the vesicourethral relaxation reflex.
      This excitatory effect of HGN stimulation was blocked by prazosin. These data
      suggest that the potential of the rhabdosphincter evoked by HGN stimulation (1
      Hz) is produced through synapse from sympathetic preganglionic to cholinergic
      postganglionic neurons, and that, after sacral rhizotomy, cholinergic
      postganglionic terminals form more effective functional connections to
      somatically denervated motor end-plates of the rhabdosphincter. The sympathetic
      nerve is also believed to play a role in modulating urethral afferent activities
      through action on urethral smooth muscle.

PMID- 8254821
TI  - Micturition and premicturition contractions in unanesthetized rats with bladder
      outlet obstruction.
AB  - The cholinergic and purinergic neurotransmission involved in micturition
      contraction and premicturition contractile activity (bladder hyperactivity) were
      investigated by continuous cystometry in unanesthetized rats with outlet
      obstruction. Adenosine triphosphate (ATP), administered intra-arterially close to
      the bladder, produced rapid, phasic dose-dependent increases in bladder pressure
      and micturition immediately after the injections. The percentage volume expelled
      was 74 +/- 9% after 5 mg/kg. Intra-arterial alpha,beta-methylene ATP also
      produced a rapid, phasic increase in bladder pressure and micturition immediately
      after the injection. The percentage volume expelled was 96 +/- 3% after 1 mg./kg;
      the residual volume of the following voidings increased, and the micturition
      pressure tended to decrease. However, dribbling incontinence was not produced.
      The amplitude of the premicturition contractions decreased significantly (p <
      0.01) after the administration. Intra-arterial carbachol produced rapid,
      longlasting dose-dependent increases in bladder pressure and micturition. The
      percentage volume expelled was 88 +/- 4 after 5 micrograms./kg. Bladder capacity
      and micturition volume decreased significantly (p < 0.05) during the following
      spontaneous voidings. Intra-arterial atropine (1 mg./kg.) increased bladder
      capacity (p < 0.01) and residual volume (p < 0.01), and tended to decrease
      micturition pressure (by 25%) and micturition volume. However, micturition
      contractions still remained after the injection, even if they changed appearance,
      and were of shorter duration. Atropine had no effect on the premicturition
      contractions. In the presence of atropine, alpha,beta-methylene ATP initially
      produced a rapid, phasic increase in bladder pressure with micturition. Then,
      dribbling incontinence was observed in 1 of 5 animals. Hexamethonium,
      administered intra-arterially in doses producing urinary retention and dribbling
      incontinence (20 or 40 mg./kg.), increased the amplitude of the premicturition
      contractions, but decreased the frequency of the contractions. Intra-arterial
      tetrodotoxin (15 micrograms./kg.) inhibited micturition, and produced dribbling
      incontinence in all animals tested (n = 6). However, the amplitude of the
      premicturition contractions was not suppressed. Intra-arterial (+/-)-pinacidil
      (0.2 mg./kg.) significantly (p < 0.05) decreased both amplitude and frequency of
      these contractions. It is concluded that both cholinergic and purinergic
      transmission seem to be of importance for pressure generation and emptying of the
      bladder in rats with outlet obstruction. The present results also give further
      support for the view that the premicturition contractions seen in these animals
      are of myogenic origin.

PMID- 8254822
TI  - Micturition patterns after spinal trauma as a measure of autonomic functional
      recovery.
AB  - The purpose of these experiments was to determine whether experimental spinal
      trauma would result in urological dysfunction similar to that seen clinically and
      whether recovery of normal micturition can be correlated with motor functional
      recovery. A standard rat model of spinal impact trauma was employed. Neurologic
      evaluation included a modified 7 point hindlimb Tarlov scale applied weekly for 4
      weeks after injury. Micturition measurement was accomplished by placing the
      animal in a metabolic cage for 24-hour periods and collecting urine on an
      electronic scale connected to Lotus Measure data acquisition software. All
      assessments were performed in a blinded fashion. Animals were categorized as
      normal control (N = 10), sham injured (N = 11), spinal cord injury (SCI) without
      (N = 11) and with locomotor recovery (N = 11). There were no differences in total
      micturition volume among the 4 groups, while the number of micturitions per 24
      hours was significantly less for SCI without locomotor recovery (10.4 +/- 5.9)
      than for control (21.3 +/- 4.5). The volume per micturition was significantly
      greater for SCI (2.0 +/- 0.7 ml.) than for control (0.8 +/- 0.2 ml.). There were
      no differences among groups in the ratio of number of micturitions night/day. The
      SCI group had significantly greater largest and smallest micturitional volumes.
      Results clearly show alterations in micturition patterns induced by SCI. These
      were proportional to, but did not correlate fully with, the severity of injury
      and degree of motor recovery. Thus, recovery of a normal micturition pattern did
      not occur to the same extent as did motor functional recovery. This difference
      underscores the potential value of autonomic measures of SCI for distinguishing
      outcome categories after experimental SCI.

PMID- 8254823
TI  - Effects of shock waves on the mouse fetus.
AB  - Extracorporeal shock wave lithotripsy is contraindicated during pregnancy because
      its effects on the fetus remain to be ascertained. The purpose of this study was
      to elucidate the effects of shock waves on fetuses at various stages of
      pregnancy. Pregnant mice received 100, 250, or 500 shock waves on 8, 10, 12, 14,
      and 16 days postcoitum. The effect on fetal survival rate and weight was minimal
      in the early stages of pregnancy. In the later stages of pregnancy, however, the
      number of viable fetuses decreased in proportion to an increasing number of shock
      waves, and almost no viable fetuses were found in the group treated with 500
      shock waves. Fusion and necrosis were found in many dead fetuses. Histological
      examination of the fetuses, which was obtained immediately after the shock wave
      treatment, revealed hemorrhages in the brain, lungs and subcutaneous tissue. This
      study indicated that shock waves lead to fetal damage and death in the late stage
      of pregnancy in mice.

PMID- 8254824
TI  - Anoxia and corporal smooth muscle dysfunction: a model for ischemic priapism.
AB  - The hemodynamics of penile flaccidity, erection and detumescence requires
      corporal smooth muscle to function across a wide variation in pO2. The present
      study describes the effect of anoxia on corporal smooth muscle response to field
      stimulation and pharmacologic agonists and antagonists of erection. The response
      of isolated strips of rabbit corpus cavernosal tissue to field stimulation,
      phenylephrine, bethanechol, ATP and KCL was determined under oxygenated and
      anoxic conditions. The results can be summarized as follows: 1) Anoxia eliminated
      spontaneous contractile activity and reduced basal tissue tension to a minimum.
      2) Neither field stimulation nor pharmacological agents (ATP, bethanechol,
      isoproterenol) could relax basal tension below that induced by anoxia alone. 3)
      Under anoxic conditions alpha-adrenergic agonists produced poorly sustained
      phasic contractile responses; anoxia eliminated tonic contractile responses to
      phenylephrine. 4) In normoxic conditions field stimulation of smooth muscle
      precontracted with phenylephrine produced frequency-dependent graded relaxations;
      under anoxic conditions field stimulation yielded contractile responses at all
      frequencies. Our data suggest that corporal smooth muscle tone, spontaneous
      contractile activity, the contractile response to alpha-agonists and field
      stimulated relaxation depend on the state of corporal oxygenation. The inability
      of alpha-stimulation to induce a tonic contraction of corporal smooth muscle
      under anoxia in vitro parallels the failure of penile injection of alpha
      adrenergic agonists to relax ischemic priapism.

PMID- 8254825
TI  - Effect of glutathione and its related enzymes on chemosensitivity of renal cell
      carcinoma and bladder carcinoma cell lines.
AB  - Glutathione and glutathione-related enzymes have been implicated in sensitivity
      of tumors to chemotherapeutic drugs. In the present study, glutathione and the
      activity of its related enzymes were quantitated in 4 renal cell carcinoma cell
      lines and 4 bladder carcinoma cell lines. The expression of glutathione-s
      transferase pi and alpha in each cell line was analyzed by immunoblot analysis.
      The relationships between glutathione levels, glutathione peroxidase activity and
      glutathione-s-transferase activity and tumor sensitivity to cisplatinum,
      doxorubicin and vinblastine were determined by linear regression analysis.
      Glutathione levels were positively related to cisplatinum resistance in both
      renal cell carcinoma and bladder carcinoma cell lines and to doxorubicin
      resistance in bladder carcinoma cell lines. A positive correlation between
      glutathione peroxidase activity and doxorubicin resistance was identified in
      renal cell carcinoma cell lines, but no correlation was noted in bladder
      carcinoma cell lines. No significant correlation was apparent between glutathione
      s-transferase activity and sensitivity to any of the drugs tested in this study.
      To further clarify the relationship between glutathione levels and the
      cytotoxicity of the drugs, we evaluated the effect of glutathione depletion by L
      buthionine sulfoximine on the cytotoxicity of the drugs in bladder carcinoma cell
      lines. Glutathione depletion enhanced cisplatinum cytotoxicity 1.3- to 1.7-fold
      and doxorubicin cytotoxicity by 1.45- to 11.2-fold. Glutathione depletion did not
      change vinblastine cytotoxicity. The present study demonstrates that glutathione
      and its related enzymes affect sensitivity to cisplatinum or doxorubicin. The
      drug resistance mechanism elicited by glutathione and its related enzymes in
      these tumors needs further elucidation so that chemotherapeutic regimens may be
      modified.

PMID- 8254826
TI  - Ureteral response to the placement of metallic stents: an animal model.
AB  - Metallic self-expanding mesh stents are increasingly used in the urinary tract.
      Little is known about the histological reactions that such prostheses have on the
      surrounding tissue. The effects of self-expanded metallic stents in the
      histologically normal ureter were examined in four dogs. Three-mm. Gianturco
      Roubin coronary artery stents were introduced into the distal left ureter after
      dilatation. Follow-up excretory urography, retrograde pyelograms and autopsy were
      performed on 2 dogs at 1 month and on 2 dogs at 6 months. In all 4 dogs, the
      ureters remained patent. Histologic examination of the ureter showed that the
      stents had not become incorporated within the wall of the ureter. Reactive
      changes seen in the epithelium included penetration of both epithelium and
      submucosa between the wire struts and areas of fibrosis in the submucosal layer.
      The use of metallic stents in histologically normal ureters may be limited in the
      long term by this inflammatory response.

PMID- 8254827
TI  - Intravesical mitomycin C and doxorubicin sequential therapy for carcinoma in situ
      of the bladder: a longer followup result.
AB  - A total of 43 patients with carcinoma in situ of the bladder (primary in 26 and
      secondary in 17) who underwent intravesical mitomycin C and doxorubicin
      sequential therapy for 2 multicenter studies were followed for a median period of
      45 months (range 10 to 84). Of the patients 32 (74%) achieved complete response
      after induction therapy and underwent maintenance therapy with either mitomycin C
      plus doxorubicin, mitomycin C alone or observation only. Of the complete
      responders 13 (41%) had a local recurrence, and subsequent repeat intravesical
      mitomycin C and doxorubicin sequential therapy as well as bacillus Calmette
      Guerin was effective in a significant proportion (75% or greater). The
      maintenance therapy did not have a favorable effect on the recurrence rate. In 8
      patients (19%) (3 of 32 complete responders and 5 of 11 nonresponders)
      progression developed, including invasive cancers in 4, metastatic disease in 2
      and both conditions in 2. Initial complete responders had a significantly higher
      progression-free rate than initial nonresponders, although there was no
      difference in the sites of progression between them. At the last followup 35
      patients (81%) remained free of disease with 31 (72%) having a normally
      functioning bladder. According to these results, intravesical mitomycin C and
      doxorubicin sequential therapy appears to be applicable as initial treatment for
      carcinoma in situ of the bladder.

PMID- 8254828
TI  - Radical cystectomy for stages Ta, Tis and T1 transitional cell carcinoma of the
      bladder.
AB  - Between January 1969 and January 1990, 531 patients underwent bilateral pelvic
      lymph node dissection and radical cystectomy for the management of transitional
      cell carcinoma of the bladder. Of these procedures 220 were performed for
      clinical stage Ta (31 patients), Tis (23) or T1 (166) disease, which was either
      high grade or recalcitrant to transurethral resection and/or intravesical
      chemotherapy. This subgroup of patients was studied to evaluate the outcome of
      recurrent or chemotherapy resistant superficial transitional cell carcinoma of
      the bladder after radical cystectomy. The operative mortality rate for the group
      was 2.3% and the overall complication rate was 20.4%. The pelvic recurrence rate
      was 5.9%. The 5-year cancer-specific survival rates for patients with
      pathological stage Ta (11), Tis (19), T0 (43) and T1 (91) disease were 88%, 100%,
      80% and 76%, respectively. The 10-year cancer-specific survival rates were 75%,
      92%, 66% and 62%, respectively. A total of 74 patients received preoperative
      radiation therapy (2,000 rad) but they had no better 5-year cancer-specific
      survival rates than did nonirradiated patients. Transurethral resection and/or
      preoperative radiation therapy resulted in a pathological status of T0 in 43
      patients but this did not confer a survival advantage. Although bladder
      preservation is preferable, low operative mortality and pelvic recurrence rates,
      as well as new methods of continent urinary diversion continue to make radical
      cystectomy the definitive form of therapy for patients with superficial disease
      recalcitrant to transurethral therapy.

PMID- 8254829
TI  - Deoxyribonucleic acid content and survival rates of patients with transitional
      cell carcinoma of the bladder.
AB  - In 127 patients with urothelial carcinoma of the bladder the ploidy,
      deoxyribonucleic acid (DNA) heterogeneity and counts of cell cycle phases in the
      tumor were analyzed by means of single cell DNA cytophotometry with the intention
      of finding new prognostic factors in addition to those already known (stage and
      grade). Patients were followed for 1 to 9 years. The results of the DNA analyses
      were related to the tumor categories, histopathological grading of the tumor and
      clinical course. Tumors were histologically classified as grade 1--DNA frequency
      peaks in the diploid range, grade 2--heterogenous DNA distribution patterns, and
      grade 3-73% aneuploid and 27% tetraploid DNA values. The proliferation rate of
      the tumor cells was statistically greater in cases of histological grades 2 and 3
      malignancy than in grade 1 malignancy. There was also a positive correlation
      between tumor stage and DNA ploidy. The cell lines were aneuploid in 38% of the
      patients with stage pT1, 64% with stage pT2 and almost 85% with stage pT3 tumors.
      A significant correlation was found between the results of DNA cytophotometry and
      the clinical course of the disease. Patients with diploid tumor cell lines had no
      metastases and no local tumor progression for up to 9 years, whereas patients
      with multiple aneuploid tumor cell lines suffered recurrence and local tumor
      progression within 6 to 36 months. On the average, the patients died of the
      tumors 26 months after primary diagnosis. The difference in tumor recurrence and
      in tumor progression between patients with aneuploid and diploid tumors was
      highly significant (p < 0.001). The prognosis for patients with grade 1 tumors is
      good, whereas it is unfavorable in the case of grade 3 tumors. For these 2 groups
      DNA ploidy affords no additional prognostic information. Grade 2 tumors, on the
      other hand, are heterogeneous in respect to DNA ploidy, although they exhibit the
      same degree of histomorphological differentiation. These tumors can be
      subclassified as aneuploid (biologically aggressive) and diploid or tetraploid
      (biologically less aggressive). In terms of multivariate Cox regression analysis,
      DNA ploidy compared with grade and tumor stage was the strongest predictor of
      survival.

PMID- 8254830
TI  - Bladder cancer.

PMID- 8254831
TI  - A high association of oncogenic human papillomaviruses with carcinomas of the
      female urethra: polymerase chain reaction-based analysis of multiple histological
      types.
AB  - Using polymerase chain reaction with type-specific human papillomavirus type 16
      and 18 primers, and general primers screening for 9 other genotypes, we analyzed
      archival surgical specimens of urethral carcinoma from 18 women (17 with invasive
      cancer and 1 with carcinoma in situ). Human papillomavirus was detected in
      invasive urethral carcinoma specimens from 10 of 17 women (59%) and in the
      patient with carcinoma in situ. Human papillomavirus type 16 was found in 8
      patients with invasive carcinoma (47%) and 1 with carcinoma in situ, and general
      primer polymerase chain reaction demonstrated human papillomavirus that could not
      be typed in 2 patients (12%). Type 16 was detected in metastases from 4 patients;
      complete concordance for the presence of human papillomavirus in primary and
      metastatic disease was noted. Eight of 10 women with squamous cell carcinoma and
      both with transitional cell carcinoma harbored human papillomavirus; 5 women with
      undifferentiated carcinoma or adenocarcinoma were all negative for human
      papillomavirus. Concurrently excised cervical tissue was available from 5
      patients; 1 had cervical carcinoma in situ positive for human papillomavirus of
      the same type as the urethral carcinoma. These findings strongly suggest that
      human papillomavirus, particularly type 16, is associated with a substantial
      number of carcinomas of the female urethra but a stratification of specific
      histotypes associated with human papillomavirus may exist.

PMID- 8254832
TI  - Effect of alkaline citrate therapy on clearance of residual renal stone fragments
      after extracorporeal shock wave lithotripsy in sterile calcium and infection
      nephrolithiasis patients.
AB  - The natural history of post-extracorporeal shock wave lithotripsy residual stone
      fragments (clearance, growth and aggregation) is incompletely known, even though
      they are believed to constitute a risk in terms of new stone formation and
      persistent infection of the urinary tract. We addressed this issue and the
      hypothesis that alkaline citrate therapy improves residual stone fragment
      clearance in a 12-month followup study. There were 40 sterile calcium and 30
      struvite stone patients with residual fragments after extracorporeal shock wave
      lithotripsy (diameter less than 5 mm.) consecutively enrolled and randomly
      assigned to a citrate therapy (6 to 8 gm. per day) or control (hygienic measures
      only) group. Infection stone patients also received adequate antibiotic therapy
      throughout the study. Among the patients in the untreated sterile group 21% and
      32% were stone-free at 6 and 12 months, respectively. In the infection group
      these figures were 27% and 40%, respectively. Among the untreated sterile calcium
      stone patients in whom clearance was not achieved a high percentage experienced
      residual fragment growth or reaggregation. Citrate therapy significantly improved
      the stone clearance rate in the sterile (at 6 and 12 months 65% and 74% were
      stone-free, respectively) and infection (71% and 86%, respectively) stone
      patients, and prevented residual fragment growth or reaggregation in subjects in
      whom clearance was not achieved. The data show that growth and persistence are
      common in the natural history of residual stone fragments. Citrate ameliorated
      the outcome of these residual fragments by reducing the growth or agglomeration,
      and by increasing the clearance rate in calcium oxalate and in infection stone
      patients.

PMID- 8254833
TI  - Impotence and its medical and psychosocial correlates: results of the
      Massachusetts Male Aging Study.
AB  - We provide current, normative data on the prevalence of impotence, and its
      physiological and psychosocial correlates in a general population using results
      from the Massachusetts Male Aging Study. The Massachusetts Male Aging Study was a
      community based, random sample observational survey of noninstitutionalized men
      40 to 70 years old conducted from 1987 to 1989 in cities and towns near Boston,
      Massachusetts. Blood samples, physiological measures, socio-demographic
      variables, psychological indexes, and information on health status, medications,
      smoking and lifestyle were collected by trained interviewers in the subject's
      home. A self-administered sexual activity questionnaire was used to characterize
      erectile potency. The combined prevalence of minimal, moderate and complete
      impotence was 52%. The prevalence of complete impotence tripled from 5 to 15%
      between subject ages 40 and 70 years. Subject age was the variable most strongly
      associated with impotence. After adjustment for age, a higher probability of
      impotence was directly correlated with heart disease, hypertension, diabetes,
      associated medications, and indexes of anger and depression, and inversely
      correlated with serum dehydroepiandrosterone, high density lipoprotein
      cholesterol and an index of dominant personality. Cigarette smoking was
      associated with a greater probability of complete impotence in men with heart
      disease and hypertension. We conclude that impotence is a major health concern in
      light of the high prevalence, is strongly associated with age, has multiple
      determinants, including some risk factors for vascular disease, and may be due
      partly to modifiable para-aging phenomena.

PMID- 8254834
TI  - A possible ontogenic etiology for idiopathic left varicocele.
AB  - A total of 659 consecutive patients underwent venography for the evaluation of
      idiopathic left varicocele before sclerotherapy. In 484 cases no valves of the
      left spermatic vein could be demonstrated, while 172 patients demonstrated
      competent valves or absent insertions of the left spermatic vein at the typical
      point on the left renal vein plus retrograde flow over persistent intercardinal
      anastomoses. Stenosis of the renal vein occurred in 103 patients (15.7%). In only
      3 patients was stenosis observed in the course of the left iliac vein, suggestive
      of the so-called distal nutcracker phenomenon. We propose that during
      embryogenesis disturbances in the development of the secondary venous system may
      result in the idiopathic left varicocele.

PMID- 8254835
TI  - Deoxyribonucleic acid ploidy in seminomas with and without syncytiotrophoblastic
      cells.
AB  - Seminomas with human chorionic gonadotropin-producing syncytiotrophoblastic cells
      have been discussed as a distinctive subgroup with a worse prognosis. In a series
      of 50 seminomas (30 with immunohistochemically detectable syncytiotrophoblastic
      cells and 20 without syncytiotrophoblastic cells) deoxyribonucleic acid (DNA)
      ploidy was determined by flow cytometry in paraffin-embedded histopathological
      material. Comparatively, in 28 cases the DNA content was assessed by image
      cytometry on Feulgen-stained slides. DNA aneuploidy was detected in 49 seminomas
      (98%). No differences in the distribution of DNA index were observed between
      cases positive and negative for syncytiotrophoblastic cells (average DNA index
      1.68 +/- 0.44 for positive cases and 1.71 +/- 0.52 for negative cases). Flow
      cytometry and image cytometry DNA index values showed a statistically significant
      correlation (p < 0.01). Intra-tumoral heterogeneity of DNA content was found in 2
      seminomas negative for syncytiotrophoblastic cells. Multiploidy and
      hypertetraploidy were noted more often in negative cases also. DNA ploidy or
      distinct aneuploid stemlines did not correlate with histopathological tumor stage
      or clinical course. The results favor the notion that the occurrence of
      syncytiotrophoblastic cells in seminomas represents only an example of intra
      tumoral variability of tumor cell differentiation and does not justify the
      definition as a separate subgroup with distinct biological behavior.

PMID- 8254836
TI  - Primary chemotherapy for stage II nonseminomatous germ cell tumors of the testis.
AB  - Between 1979 and 1989, 122 patients with clinical stage II testicular nonseminoma
      were treated with primary platinum-based combination chemotherapy following
      orchiectomy. Of the patients 58 had Royal Marsden Hospital stage IIA (nodes less
      than 2 cm. in diameter) and the other 64 had stage IIB (nodes 2 to 5 cm.
      diameter) disease. With a median followup after chemotherapy of 5.5 years, 118
      patients (97%) were disease-free. Two patients died of progressive germ cell
      tumors, 1 of bleomycin toxicity and 1 of coincidental disease. The 5-year
      actuarial survival probability was 95% (95% confidence intervals 91 to 99%) and
      the 5-year failure-free survival probability was 92% (95% confidence intervals 88
      to 97%). Tumor substage was not predictive of relapse but did indicate the
      probability of lymphadenectomy for a post-chemotherapy residual mass since this
      was performed in 17% of the patients with stage IIA disease and 39% with stage
      IIB disease (p < 0.05). Resected specimens contained mature teratoma (29),
      necrosis alone (5) or embryonal carcinoma (1). We conclude that for these
      clinical stages primary chemotherapy was as effective as primary lymph node
      dissection and a major operation was avoided in 68% of the cases.

PMID- 8254837
TI  - A piece of my mind. Joshua knew.

PMID- 8254838
TI  - Animals and science benefit from 'replace, reduce, refine' effort.

PMID- 8254839
TI  - Scientists still debate the fate of smallpox virus.

PMID- 8254840
TI  - Rotary clubs offer help in preschool immunization.

PMID- 8254841
TI  - From the Congressional Office of Technology Assessment.

PMID- 8254842
TI  - From the Centers for Disease Control and Prevention. Severe acute respiratory
      illness linked to use of shoe sprays--Colorado, November 1993.

PMID- 8254843
TI  - From the Centers for Disease Control and Prevention. Mortality patterns--United
      States, 1991.

PMID- 8254844
TI  - The treatment of mild hypertension study.

PMID- 8254845
TI  - Peak bone mineral density in young women.

PMID- 8254846
TI  - Teaching good transfusion practices.

PMID- 8254847
TI  - Transfused stored blood and oxygen delivery in patients with sepsis.

PMID- 8254848
TI  - US hospital ships: more public health, less high tech.

PMID- 8254849
TI  - Coronary artery bypass graft mortality: patient risk of physician practice?

PMID- 8254850
TI  - Blood donation by patients with hemochromatosis.

PMID- 8254851
TI  - Blood donation by patients with hemochromatosis.

PMID- 8254852
TI  - Hepatitis B vaccine responsiveness in Connecticut public safety personnel.
AB  - OBJECTIVE: To determine the level and determinants of vaccine response in
      recently inoculated public safety personnel. DESIGN: Prevalence survey.
      PARTICIPANTS: Public safety personnel who had completed vaccination 1 to 6 months
      prior to testing and had no serological evidence of previous exposure to
      hepatitis B virus. MAIN OUTCOME MEASURE: An inadequate level of antibody to
      hepatitis B surface antigen was defined as less than 10 mlU/mL. RESULTS: All
      subjects in the study had been vaccinated using Recombivax HB, a recombinant
      hepatitis B vaccine. Of 528 individuals, 11.9% were found to have no or
      inadequate levels of antibody. The frequency of inadequate level of antibody
      increased significantly relative to age, from 2.8% among those younger than 30
      years to 42.1% among those older than 60 years (P < .0001). Smoking (odds ratio
      [OR], 3.6; 95% confidence interval [CI], 2.0 to 6.4), extreme obesity (OR, 13.3;
      95% CI, 3.8 to 49.1), and increasing time interval since completing the vaccine
      series (P < .01) were also associated with inadequate levels of antibody. These
      findings were confirmed by multivariate analysis using logistic regression.
      CONCLUSIONS: Routine immunization of public safety personnel should include
      selective use of postvaccine testing. Postvaccination testing optimally should be
      performed in the 30- to 90-day interval after the last vaccine dose. New
      vaccination strategies are needed to improve response rates in persons with
      predictably poor response to hepatitis B vaccine.

PMID- 8254853
TI  - Risk factors for lack of detectable antibody following hepatitis B vaccination of
      Minnesota health care workers.
AB  - OBJECTIVE: To assess the presence of antibody to hepatitis B surface antigen
      (anti-HBs) at postvaccination testing in Minnesota health care workers receiving
      recombinant hepatitis B vaccines, and to identify risk factors for lacking anti
      HBs following hepatitis B vaccination. DESIGN: Retrospective cohort study.
      SETTING: Ten acute care hospitals in Minnesota. PARTICIPANTS: A total of 595
      health care workers who had received hepatitis B vaccine (Recombivax HB or
      Engerix-B) between June 1987 and December 1991 and who underwent postvaccination
      testing for anti-HBs within 6 months after receiving the third dose of vaccine.
      MAIN OUTCOME MEASURE: Presence or absence of anti-HBs following hepatitis B
      vaccination. RESULTS: Five variables were independently associated with lacking
      anti-HBs by multivariate analysis: vaccine brand, smoking status, gender, age,
      and body mass index. Stratifying by vaccine brand demonstrated that age (P =
      .01), body mass index (P < .01), and smoking status (P < .01) were associated
      with lacking anti-HBs only for Recombivax HB recipients; and gender (P = .03) was
      associated with lacking anti-HBs only for Engerix-B recipients. After controlling
      for smoking status, age, gender, and body mass index, recipients of Recombivax HB
      were more likely to lack anti-HBs than recipients of Engerix-B (relative risk,
      2.3; 95% confidence interval, 1.1 to 4.7; P = .02). CONCLUSIONS: Results indicate
      that certain populations of health care workers are at increased risk of not
      responding to hepatitis B vaccination. Further studies evaluating immunogenicity
      of currently available recombinant hepatitis B vaccines in persons at high risk
      for primary vaccine failure are needed.

PMID- 8254854
TI  - Fetal loss associated with caffeine intake before and during pregnancy.
AB  - OBJECTIVE: To determine if caffeine intake before and during pregnancy was
      associated with an increased risk for fetal loss. DESIGN: Incidence-density case
      control study. SETTING: University-affiliated obstetric and pediatric hospital in
      Montreal, Quebec. PARTICIPANTS: A total of 331 women with fetal loss and 993
      controls with a normal pregnancy at the same period of pregnancy as the case.
      OUTCOME MEASURES: Crude and adjusted odds ratios (ORs) for fetal loss were
      estimated using conditional logistic regression. A trend test for increasing
      caffeine intake was also used. RESULTS: Caffeine intake was divided into
      quartiles; the baseline for comparison was less than 48 mg per day. The adjusted
      ORs for fetal loss associated with caffeine intake before pregnancy were 1.29
      (95% confidence interval [CI], 0.85 to 1.95) for 48 to 162 mg; 1.37 (95% CI, 0.92
      to 2.04) for 163 to 321 mg; and 1.85 (95% CI, 1.18 to 2.89) for more than 321 mg.
      The same comparisons were made for caffeine intake during pregnancy, and the
      respective adjusted ORs were 1.15 (95% CI, 0.82 to 1.63), 1.95 (95% CI, 1.29 to
      2.93), and 2.62 (95% CI, 1.38 to 5.01). After controlling for confounding
      factors, there was a strong association of caffeine intake during pregnancy and
      fetal loss, compatible with a linear trend on the logistic scale in which ORs
      increased by a factor of 1.22 (1.10 to 1.34) for each 100 mg of caffeine ingested
      daily during pregnancy. CONCLUSIONS: Caffeine intake before and during pregnancy
      was associated with an increased risk of fetal loss, supporting the US Food and
      Drug Administration recommendation to pregnant women, largely based on animal
      studies, to reduce their caffeine intake.

PMID- 8254855
TI  - Cardiac transplantation for infants with hypoplastic left-heart syndrome.
AB  - OBJECTIVE: To determine whether cardiac transplantation improves the natural
      history of infants with hypoplastic left-heart syndrome and to examine
      differences in outcome as a function of the pretransplant period. DESIGN:
      Retrospective cohort study. Historical, clinical, and laboratory data were
      collected during the pretransplant period, the in-hospital period, and for up to
      6 years following transplantation. Data were analyzed using the product-limit
      estimate and the log rank test. SETTING: A tertiary, acute care, university
      teaching hospital. PATIENTS: All 111 infants with hypoplastic left-heart syndrome
      who entered and completed a protocol leading to transplantation from November 19,
      1985, to December 31, 1991. Infants who died while waiting for transplantation
      were included. INTERVENTION: Orthotopic cardiac allotransplantation. MAIN OUTCOME
      MEASURES: Pretransplant waiting mortality and its influence on posttransplant
      survival, operative (in-hospital or within 30 postoperative days in discharged
      patients) and intermediate-term mortality (5 years), and reoperation rates for
      cardiac surgery. RESULTS: Transplantation procedures were performed in 84 infants
      (76%; 95% confidence interval [CI], 66% to 83%) ranging in age from 3 hours to
      151 days. Twenty-seven infants registered for transplantation died while awaiting
      a donor heart. Operative mortality was 13% (CI, 7% to 23%), and 69 patients were
      late survivors (62% [CI, 52% to 71%] of the study group and 82% [CI, 72% to 89%]
      of the transplant recipients). Overall 5-year actuarial survival was 61% (CI, 52%
      to 70%). Transplant recipients had a 5-year survival of 81% (CI, 71% to 88%).
      Freedom from reoperation was 89% (CI, 76% to 95%) at 5 years. CONCLUSIONS:
      Cardiac transplantation for hypoplastic left-heart syndrome has a significant
      positive impact on the natural history of this uniformly lethal lesion.

PMID- 8254856
TI  - National policy development for the clinical application of genetic diagnostic
      technologies. Lessons from cystic fibrosis.
AB  - In recognition of the earlier experiences with genetic diagnostic services and in
      anticipation of a greater potential for genetic testing for presymptomatic
      disease and disease susceptibility, this article provides an analysis of policy
      development for cystic fibrosis carrier screening. The deficiencies of relying on
      an extemporaneous model for health policy development are described. Preferably,
      an evidentiary model, based on the evaluation of clinical research and
      incorporating professional and public attention to underlying normative issues,
      should define the standard of care. Appropriate procedural mechanisms should be
      established at both state and federal levels to prevent the unnecessary
      confusion, expense, and personal or social harms likely to result from a
      completely unrestrained application of developing genetic technologies or
      continuing ad hoc responses to rapid increases in genetic diagnostic
      capabilities. A broadly constituted national advisory commission on the ethical,
      legal, and social implications of the Human Genome Project would provide an
      important locus for national decision making and may offer an efficient mechanism
      for implementing the evidentiary model, promoting public involvement at a time
      when social policy decisions must be made to restructure the health care system
      to be more sensitive to issues of access, allocation, and costs.

PMID- 8254857
TI  - Breath alcohol values following mouthwash use.
AB  - OBJECTIVE: To determine whether breath alcohol values (BrAV) attained following
      mouthwash use pose a realistic threat to the accuracy of blood alcohol
      determinations by breath analysis. DESIGN: Nonrandomized, open-label trial.
      SETTING: Outpatient research office. PARTICIPANTS: Ten normal subjects;
      convenience sample. INTERVENTIONS: Breath alcohol measurements were made 2, 4, 6,
      10, and 15 minutes following rinsing of the mouth with Listerine (26.9% alcohol)
      [corrected], Scope (18.9% alcohol), and Lavoris (6.0% alcohol) using the Alco
      Sensor III intoximeter. MAIN OUTCOME MEASURES: Breath alcohol values over time.
      RESULTS: Breath alcohol values following mouthwash use decayed exponentially (r2
      > or = .98, P < .001) from mean values 2 minutes following mouthwash use of 52.8
      mmol/L (240 mg/dL) for Listerine, 37.4 mmol/L (170 mg/dL) for Scope, and 7.9
      mmol/L (36 mg/dL) for Lavoris to mean and maximum values after 10 minutes that
      were well below the usual driving-while-intoxicated range (> or = 17.6 mmol/L [80
      mg/dL]) for all three brands. The nonalcoholic mouthwash ingredients did not
      significantly affect the BrAVs attained. CONCLUSION: The decay of BrAVs following
      mouthwash use is sufficiently rapid that mouthwash use would not pose a realistic
      threat to the accuracy of blood alcohol determinations by breath analysis under
      normal circumstances. Use of mouthwash immediately prior to breath testing, as
      might occur in the car or workplace in a mistaken attempt to hide the smell of
      alcohol or other substances, may, however, significantly increase the measured
      BrAV.

PMID- 8254858
TI  - A new Simplified Acute Physiology Score (SAPS II) based on a European/North
      American multicenter study.
AB  - OBJECTIVE: To develop and validate a new Simplified Acute Physiology Score, the
      SAPS II, from a large sample of surgical and medical patients, and to provide a
      method to convert the score to a probability of hospital mortality. DESIGN AND
      SETTING: The SAPS II and the probability of hospital mortality were developed and
      validated using data from consecutive admissions to 137 adult medical and/or
      surgical intensive care units in 12 countries. PATIENTS: The 13,152 patients were
      randomly divided into developmental (65%) and validation (35%) samples. Patients
      younger than 18 years, burn patients, coronary care patients, and cardiac surgery
      patients were excluded. OUTCOME MEASURE: Vital status at hospital discharge.
      RESULTS: The SAPS II includes only 17 variables: 12 physiology variables, age,
      type of admission (scheduled surgical, unscheduled surgical, or medical), and
      three underlying disease variables (acquired immunodeficiency syndrome,
      metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated
      that the model performed well in the developmental sample and validated well in
      an independent sample of patients (P = .883 and P = .104 in the developmental and
      validation samples, respectively). The area under the receiver operating
      characteristic curve was 0.88 in the developmental sample and 0.86 in the
      validation sample. CONCLUSION: The SAPS II, based on a large international sample
      of patients, provides an estimate of the risk of death without having to specify
      a primary diagnosis. This is a starting point for future evaluation of the
      efficiency of intensive care units.

PMID- 8254859
TI  - Health care unreform. The New Jersey approach.

PMID- 8254860
TI  - Host factors related to poor immunogenicity of hepatitis B vaccine in adults.
      Another reason to immunize early.

PMID- 8254861
TI  - Caffeine during pregnancy: grounds for concern?

PMID- 8254862
TI  - Diagnostic and therapeutic technology assessment. Human papillomavirus DNA
      testing in the management of cervical neoplasia.

PMID- 8254863
TI  - Opinions of Dutch physicians, nurses, and citizens on health care policy,
      rationing, and technology.

PMID- 8254864
TI  - [Mechanisms of action of volatile anesthetics on smooth muscle].
AB  - The development of intracellular Ca2+ fluorescent indicators and specific
      enzymatic substances as well as the application of the patch-clamp method have
      made it possible to clarify the mechanisms of action of volatile anesthetics
      inhibit smooth muscle contraction in part by decreasing intracellular Ca2+
      concentration ([Ca2+]i); this effect is mediated by blocking calcium channels,
      especially the L-type voltage-operated channel, and by raising the intracellular
      cyclic AMP and cyclic GMP levels. Volatile anesthetic-induced suppression of
      smooth muscle contraction is also attributable to mechanisms independent of
      [Ca2+]i, which involve the depression of Ca2+ sensitization mediated by C kinase.

PMID- 8254865
TI  - [Influence of posture changes on hemodynamics under fentanyl-diazepam anesthesia-
      effects of nitrous oxide].
AB  - Patients for myocardial revascularization were divided into 50% oxygen-50%
      nitrogen group (group A) and 50% oxygen-50% nitrous oxide group (group B)
      according to the kind of gas administered after the induction of anesthesia.
      Anesthetic induction was carried out with fentanyl and diazepam in both groups.
      With sufficient hemodynamic stabilization following the induction of anesthesia,
      the hemodynamic parameters were measured in supine position for baseline data
      (BASELINE). The operating table was kept at Trendelenburg position (TREND), i.e.,
      head down position, to measure hemodynamic parameters. Next, the operating table
      was kept at Fowler position (FOW), i.e., head up position, and hemodynamic
      parameters were measured. Heart rate was little influenced by posture change in
      both groups. While mean arterial pressure, mean pulmonary arterial pressure,
      central venous pressure and pulmonary capillary wedge pressure increased
      significantly in TREND in both groups, and decreased significantly in FOW.
      Cardiac index increased significantly in TREND in group A, but no such change
      occurred in group B. In FOW, cardiac index showed no significant change in group
      A, but decreased significantly in group B. Systemic vascular resistance was
      little influenced by posture change in both groups. This study suggests that it
      is necessary to exert a great caution in administering nitrous oxide when posture
      change is needed under fentanyl-diazepam anesthesia.

PMID- 8254866
TI  - [Comparison of the severity of postoperative pain in patients after thoracic,
      upper abdominal or lower abdominal surgery].
AB  - Different factors influence the severity of postoperative pain. Personality and
      cultural factors as well as anxiety and fear modify the degree of postoperative
      pain. The site of surgery is also a major determinant. We evaluated the severity
      of postoperative pain in patients after three different surgeries, thoracic,
      upper abdominal and lower abdominal surgeries, from 24 h to 72 h postoperatively.
      Thirty patients were divided into three groups: thoracic, upper abdominal and
      lower abdominal groups (n = 10, respectively). All patients received continuous
      epidural infusion of 0.25% bupivacaine (2 ml.h-1) and buprenorphine (0.2 mg x 24
      h-1). Additional analgesics were given when the patient complained of pain.
      Analgesia was evaluated by 100 mm visual analog scale and demands of analgesics.
      Pain scores at rest were not different among three groups. Pain after lower
      abdominal surgery tended to be less severe compared with that after thoracic
      surgery. Demands of analgesics were not different among three groups at any
      evaluated point. Pain after thoracic surgery was consistent during 72
      postoperative hs, but in the upper and lower abdominal surgery groups pain at 72
      hs was significantly weaker than that at 24 hs. We conclude that postoperative
      pain was not different among the three surgery groups, but pain after upper and
      lower abdominal surgery decreased more rapidly compared with that after thoracic
      surgery.

PMID- 8254867
TI  - [Efficacy of stellate ganglion block judged by quantitative measurement of
      perspiration].
AB  - Sudomotor function tests provide information on the activation of the sympathetic
      efferent fibers. We have studied the efficacy of stellate ganglion block (SGB) by
      assessment of changes in perspiration of the thumb in 10 patients. SGB was
      performed at C7 with 6 ml of 1% mepivacaine, and perspiration was induced by
      mentally stressful conversation and having patients draw up their knees for
      physical stress. Suzuken Kenz Perspiro OSS-100 was used for quantitative
      detection of perspiration. The value before SGB was 1.49 +/- 0.46 mg.3 min-1, and
      it showed a statistically significant decrease to 0.73 +/- 0.33 mg.3 min-1 10 min
      after SBG (P < 0.01). The present study suggests that quantitative measurement of
      perspiration is useful to judge the effects of SGB on arm.

PMID- 8254868
TI  - [Effect of cardiopulmonary bypass on the renal tubular cell--the importance of
      the changes in the ratio of creatinine to blood urea nitrogen].
AB  - We examined the effect of cardiopulmonary bypass on the renal tubular cell in 19
      adult patients undergoing cardiac surgery. The ratio of creatinine to blood urea
      nitrogen (BUN/Cr) decreased in the early period of cardiopulmonary bypass,
      because of increased serum creatinine and unchanged blood urea nitrogen. N-acetyl
      beta-D-glucosaminidase (NAG) index in the intra- and postbypass period was higher
      than that in the preoperative period. Creatinine clearance (CCr) on the 7th
      postoperative day and the difference of BUN/Cr between preoperative period and 30
      min after initiation of cardiopulmonary bypass (delta BUN/Cr 30 min) correlated
      significantly with the postoperative NAG index. The results suggest that
      cardiopulmonary bypass impaired the renal tubular cell, and renal tubular injury
      deteriorated the glomerular filtration in the postbypass period, and that
      creatinine production increased in the early period of cardiopulmonary bypass.
      delta BUN/Cr 30 min may predict the intraoperative renal tubular injury.

PMID- 8254869
TI  - [Assessment of left ventricular contractility (Emax) and arterial load (Ea) in
      humans by transesophageal echocardiography and radial artery pressure tracing].
AB  - We determined both the slope of the left ventricular end-systolic pressure-volume
      relation (Emax), which is a measure of contractility independent of loading
      conditions, and the slope of the arterial end-systolic pressure-stroke volume
      relation (Ea), which is a measure of arterial load independent of ventricular
      function, in 10 patients undergoing elective noncardiac surgery. Left ventricular
      end-systolic volume (Ves) was measured by transesophageal echocardiography and
      instantaneous left ventricular end-systolic pressure (Pes) was estimated from the
      dicrotic notch pressure in the radial artery. Emax was calculated during
      afterload reduction (nicardipine 30 micrograms.kg-1 iv), and the correlation of
      Emax to either Pes/Ves ratio or MAP (mean arterial blood pressure)/Ves ratio was
      accomplished in order to investigate whether these indices were clinically useful
      measurements of ventricular function or not. Ea was also calculated from the data
      obtained before and 2-3 min after nicardipine iv. The averaged Emax and x-axis
      intercept (Vo) were 3.11 mmHg.ml-1 and -3.8 ml, respectively. The correlation
      coefficient obtained between Emax and Pes/Ves was 0.96, and that obtained between
      Emax and MAP/Ves was 0.97. Ea decreased significantly (P < 0.05) following
      intravenous nicardipine, demonstrating a decreased arterial load. The direction
      of changes in Ea was similar to that reported previously in systemic vascular
      resistance. From these results, we conclude that measurement of Emax (or Pes/Ves,
      MAP/Ves) and Ea using transesophageal echocardiography and radial artery pressure
      tracing is feasible and these are a useful tool to estimate left ventricular
      performance and arterial load during surgery.

PMID- 8254870
TI  - [Continuous epidural buprenorphine for postoperative pain relief in patients
      after lower abdominal surgery].
AB  - Postoperative analgesia with epidurally injected buprenorphine and its side
      effects were investigated in 100 patients who had received lower abdominal
      surgery. All patients received initially 8 ml of bupivacaine and 0.1 mg of
      buprenorphine. Following bolus epidural injection, five different groups of 20
      patients each received either bupivacaine alone (group A), 5 micrograms.ml-1
      buprenorphine.bupivacaine mixture (group B), 8 micrograms.ml-1
      buprenorphine.bupivacaine mixture (group C), 12 micrograms.ml-1
      buprenorphine.bupivacaine mixture (group D), or 15 micrograms.ml-1
      buprenorphine.bupivacaine mixture (group E) by a portable disposable device at a
      rate of 1 ml.h-1 for 48 h. The analgesic efficacy in group E was superior to
      those in groups A, B, C or D. No significant difference in the incidence of side
      effect was found among groups C, D, E. We conclude that a dose of a approximately
      15 micrograms.h-1 might be optimal for postoperative pain relief after lower
      abdominal surgery.

PMID- 8254871
TI  - [Patient-controlled analgesia with epidural pethidine or buprenorphine plus
      bupivacaine for postoperative analgesia].
AB  - We evaluated the efficacy of epidural patient-controlled analgesia (PCA) with
      pethidine or buprenorphine plus 0.25% bupivacaine for postoperative analgesia
      after laparotomy with a midline incision under general anesthesia. Twenty
      patients were randomly allocated to two groups. In one group (PCEA-P group; n =
      10), epidural pethidine plus 0.25% bupivacaine by PCA with 5 mg of pethidine and
      2.5 ml of 0.25% bupivacaine bolus with a lockout interval of 20 min was added to
      a continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) plus pethidine
      (100 mg.24h-1) for 72 h. In the other group (PCEA-B group; n = 10), epidural
      buprenorphine plus 0.25% bupivacaine by PCA with 0.03 mg of buprenorphine and 2.5
      ml of 0.25% bupivacaine bolus with a lockout interval of 20 min was added to a
      continuous epidural infusion of 0.25% bupivacaine (2 ml.h-1) and buprenorphine
      (0.6 mg.24 h-1) for 72 h. Analgesia was evaluated by 100 mm visual analog scale
      and verbal descriptor scale. In PCEA-B group, 90% of the patients did not
      complain of pain at rest, and in PCEA-P group, all the patients did not complain
      of pain at rest for 72 h. There were no significantly different analgesic effects
      between PCEA-P and PCEA-B for 48 h. The average doses of epidural PCA were 1.9
      mg.kg-1.24 h-1 of pethidine, and 0.012 mg.kg-1.24 h-1 of buprenorphine,
      respectively. We conclude that PCEA-P and PCEA-B were effective for postoperative
      pain to the same degree for the first 48 h, but PCEA-P was superior to PCEA-B for
      the last 24 h.

PMID- 8254872
TI  - [Spread of spinal anesthesia with 0.5% isobaric bupivacaine].
AB  - The effects of age, weight, height, weight.height ratio, and body mass index on
      the spread of spinal anesthesia with 3.0 ml of 0.5% isobaric bupivacaine was
      examined in 185 patients. No significant correlation was found between the spread
      of analgesia and the age, weight, height, weight.height ratio, or body mass
      index. A significant correlation was found between the decrease in mean arterial
      pressure and the height of sensory analgesia (rho = -0.21, P < 0.05) as well as
      the aging (rho = -0.35, P < 0.001).

PMID- 8254873
TI  - [Is thoracic epidural anesthesia beneficial to myocardial ischemia?--Influence of
      hemodynamics].
AB  - The effects of thoracic epidural anesthesia (TEA) on regional myocardial blood
      flow (RMBF) and hemodynamics were evaluated in open-chest dogs with coronary
      artery stenosis. In the 6 dogs with pressure-rate quotients (PRQ) of greater than
      0.8, TEA caused a significant increase of the ratio of endocardial to epicardial
      RMBF in the ischemic region and tended to increase the ratio of RMBF in the
      ischemic to normal area, resulting in improved myocardial ischemia. There was no
      reduction of myocardial ischemia in the 11 dogs with PRQ of less than 0.8. The
      hemodynamic effects determine whether TEA is favorable for the ischemic heart or
      not. It appears that PRQ is useful as an indicator of myocardial oxygen balance
      during TEA.

PMID- 8254874
TI  - [Effects of ulinastatin on rat renal energy metabolism around ischemia studied by
      31P MRS].
AB  - The effects of ulinastatin (UTI) on rat renal energy metabolism during ischemia
      and reperfusion were studied by 31P nuclear magnetic resonance spectroscopy (31P
      MRS) in vivo. Rat kidney was exposed to ischemia for 30 min by clamping the
      abdominal aorta above the renal arteries. Pre-ischemic administration of UTI
      inhibited the decline of intracellular pH (pHi) during ischemia and improved the
      recovery of renal energy metabolism and pHi after reperfusion. This result
      suggests that UTI might inhibit anaerobic metabolism during renal ischemia and an
      improve energy metabolism during reperfusion. 31P MRS provided a unique tool to
      study intact cellular function continuously in noninvasive fashion, allowing
      assessment of metabolic function during ischemia and after reperfusion.

PMID- 8254875
TI  - [Effects of sevoflurane on spinal dorsal horn WDR neuronal activity in cats].
AB  - The effects of sevoflurane (S) (0.5%, 1.5%, and 2.5%) on the spinal dorsal horn
      wide dynamic range (WDR) neuronal activity were studied in either spinal cord
      intact or spinal cord transected cats. Extracellular activity was recorded in the
      dorsal horn from single WDR neurons responding to noxious and non-noxious stimuli
      applied to the cutaneous receptive fields on the left hind paw foot pads of
      intact or decerebrate and spinal cord transsected (L1-2) cats. When BK 10
      micrograms was injected into the femoral artery ipsilateral to the recording site
      as the noxious test stimulus in the spinal cat, 7 of 8 WDR neurons gave
      excitatory responses which were not depressed by sevoflurane 0.5% and 1.5% but
      were depressed significantly by 2.5%. On the other hand, when BK 10 micrograms
      was injected into the femoral artery ipsilateral to the recording site in the
      intact cat, 6 of 13 WDR neurons (46%) gave excitatory responses, which were
      significantly depressed by sevoflurane 0.5%, 1.5% and 2.5%, and 7 of 13 WDR
      neurons (54%) gave inhibitory responses, which were significantly depressed
      sevoflurane at 0.5%, 1.5%, and 2.5%. In conclusion, we have found that
      sevoflurane reduces the excitation as well as the inhibition of dorsal horn WDR
      neuronal activity induced by BK injection.

PMID- 8254876
TI  - [Effect of sevoflurane on contraction and membrane potentials in canine right
      ventricular myocytes].
AB  - The effects of sevoflurane on contraction and membrane potentials were studied in
      isolated canine ventricular muscle strips. Sevoflurane depressed electrically
      induced contraction in a dose-dependent manner. The inhibitory effect was more
      pronounced in high-K+ Tyrode solution than in normal Tyrode solution suggesting
      that sevoflurane inhibits transmembrane Ca2+ influx. In electrophysiological
      studies, sevoflurane depressed both overshoot and the plateau phase of action
      potentials. Resting membrane potential was not affected by sevoflurane. We
      conclude that the depression of myocardial contractility by sevoflurane may be
      due to block of transmembrane calcium influx.

PMID- 8254877
TI  - [Effects of laryngeal mask airway on circulation and on incidence of
      postoperative sore throat and hoarseness].
AB  - We studied the effects of laryngeal mask airway (LM) insertion on circulation and
      on the incidence of postoperative sore throat or hoarseness as compared with
      tracheal intubation in 50 pediatric patients. LM insertion caused less change of
      heart rate and systolic blood pressure than tracheal intubation. The incidence of
      postoperative sore throat and hoarseness was less in the patient of LM group. We
      conclude that LM is useful in pediatric anesthesia when less circulatory changes
      are desirable or when the postoperative sore throat or hoarseness is to be
      avoided.

PMID- 8254878
TI  - [Anesthetic management of a patient with hyperkalemic tubular acidosis].
AB  - We experienced the anesthetic management of a 72-year-old female with
      hyperkalemia, metabolic acidosis and renal insufficiency, undergoing right total
      hip replacement for rheumatic arthritis. She had been treated with nonsteroidal
      anti-inflammatory drugs (NSAIDs) for last several years. Anesthesia was
      maintained with isoflurane 0.2-1.0% and nitrous oxide in oxygen supplemented with
      vecuronium. Continuous infusion of prostaglandin E1 0.05-0.10 microgram.kg-1 x
      min-1 and bolus infusion of 7.0% NaHCO3 during the operation were useful in
      controlling blood pressure, improving hyperkalemia and maintaining renal
      function. Postoperatively, she was diagnosed to have hyperkalemic tubular
      acidosis due to interstitial nephritis induced by NSAIDs.

PMID- 8254879
TI  - [Anesthetic management of patients with pheochromocytoma for adrenalectomy using
      balanced anesthesia with continuous infusion of nicardipine and nitroglycerin].
AB  - Four patients underwent surgical removal of pheochromocytoma under balanced
      anesthesia with fentanyl, sevoflurane and epidural anesthesia combined with
      continuous infusion of nicardipine and nitroglycerin. Circulation was stable
      during the operation in all the patients. There were no serious hypertension and
      hypotension, arrhythmia and pulmonary edema during the postoperative period. We
      conclude that the anesthetic management of patients with pheochromocytoma for
      adrenalectomy using balanced anesthesia with continuous infusion of nicardipine
      and nitroglycerin is one of the most useful anesthetic methods.

PMID- 8254880
TI  - [Anesthetic management of a patient with a history of right upper lobectomy for
      esophageal resection via left thoracotomy].
AB  - We anesthetized a patient for esophageal resection in a right lateral decubitus
      position, because of his right pleural adhesion after lobectomy for tuberculosis.
      Although hypoxemia was expected on left lung compression during the surgery,
      oxygenation was not compromised. A good ventilation/perfusion relationship might
      have been maintained in both the right and left lungs during the procedure.

PMID- 8254881
TI  - [Anesthetic management for pacemaker implantation of a child with hypertrophic
      cardiomyopathy and sick sinus syndrome].
AB  - A 5-year-old boy weighing 15 kg with hypertrophic cardiomyopathy and sick sinus
      syndrome was scheduled to undergo implantation of permanent pacemaker without a
      temporary intravenous pacemaker, because he frequently complained of chest pain
      and fell into syncope due to hypotension associated with tachycardia when he was
      agitated. Thus, the most important point in the anesthetic management of this
      patient was to avoid tachycardia prior to and during general anesthesia. After
      the patient was premedicated with oral pentobarbital 50 mg and intramuscular
      morphine 3 mg, he seemed to be calm in the operating room. General anesthesia
      could be smoothly induced and maintained with halothane, nitrous oxide and
      fentanyl. During anesthesia, inspired concentration of halothane was chosen on
      the basis of Q-F time (the time between Q wave on the electrocardiogram and the
      initial upstroke of arterial pressure wave). The anesthetic course was
      uneventful. In this case an appropriate preanesthetic medication appeared to be
      essential, and the measurement of Q-F time was useful for the anesthetic
      management.

PMID- 8254882
TI  - [A case of massive hemorrhage associated with the removal of longstanding
      intrabronchial foreign body].
AB  - A 46 year old male patient was admitted with fever and cough. A chest X-ray film
      revealed a foreign body shadow of a denture fragment in the right intermediate
      bronchus that he had swallowed one year and half ago. Rigid bronchoscopy was used
      to remove the foreign body under general anesthesia. During the procedure,
      massive hemorrhage occurred from bronchus, and the foreign body was not removed
      successfully and the patient sustained near cardiac arrest. Postoperatively, he
      recovered from the near fatal condition with support of mechanical ventilation in
      ICU for several days. After one month, pulmonary angiography was performed and it
      revealed the transfiguration of pulmonary artery and other vessels close to the
      foreign body. Granular tissue around the foreign body was observed by
      preoperative bronchoscopy. Disruption of such vessels and granular tissue by
      rigid and forced fiberscopy was suspected to have caused the massive bleeding.
      Later, the denture fragment was successfully removed by right thoracotomy. We
      should take this complication into consideration and preoperative fiberoptic
      bronchoscopy and pulmonary angiography may be beneficial to the anesthetic
      management of such patients.

PMID- 8254883
TI  - [Postoperative disturbance of consciousness due to tumor emboli of the orifice of
      pulmonary artery].
AB  - We reported a case of an abrupt hypotension and hypoxemia which lasted more than
      60 min due to emboli of tumor at the orifice of the pulmonary artery during
      operation. Although the emboli were removed under the cardiopulmonary bypass
      (CPB) and later the patient regained good respiratory and hemodynamic conditions,
      he had a disturbance of consciousness after the operation. We began oxygen
      hyperbaric therapy (OHP) from the 6th postoperative day under spontaneous
      ventilation. His consciousness improved quickly after the beginning of OHP. We
      conclude that OHP and CPB might be useful to treat the postoperative disturbance
      of consciousness due to hypotension and hypoxemia during operation.

PMID- 8254884
TI  - [Three case reports of the use of stellate ganglion block for the climacteric
      psychosis].
AB  - There are many reports of the use of stellate ganglion block (SGB) for the
      climacteric psychosis, which is considered to be sympathicotonic response to
      stress. We experienced three cases of the SGB therapy for the climacteric
      psychosis. We performed SGB three times per week by 1% lidocaine 5 ml, and
      observed improvements of the symptoms after doing SGB for five times. The
      patients reported psychological relaxation after receiving SGB therapy. We
      examined the changes of the serum concentrations of ACTH, LH, FSH, and
      catecholamines (epinephrine, norepinephrine) before and after SGB in 8 patients
      who were suffering from climacteric psychosis, because we wanted to know the
      endocrinological response to SGB. We observed a significant decrease in
      norepinephrine concentration after SGB, which is reasonable considering the
      sympathetic blockage. There were no significant changes of ACTH, LH, FSH, and
      epinephrine. We conclude that SGB therapy must be effective for the climacteric
      psychosis because of sympathetic blockade. But we could not clarify the influence
      of endocrinological response to SGB.

PMID- 8254885
TI  - [Studies on fatigue and stress of anesthesiologist during anesthetic works using
      Holter ECG].
AB  - We evaluated fatigue, stress and workload of anesthesiologists during anesthetic
      works using Holter ECG. Recorded heart rates of anesthesiologists enable us to
      draw the task graph and to calculate the workload scores according to their task
      behavior. We conclude that the application of Holter ECG is useful in measuring
      the fatigue, stress, and especially workload of anesthesiologists.

PMID- 8254886
TI  - [Ceftibuten].

PMID- 8254887
TI  - [Antibacterial activities of cefmenoxime against recent clinical isolates from
      patients of otitis media and otitis externa].
AB  - Bacteria clinically isolated from patients of otitis media and otitis externa
      were collected from various medical facilities across Japan during years 1988,
      1990 and 1992, and minimum inhibitory concentrations (MICs) of cefmenoxime and of
      reference drugs were determined against these strains. A comparative analyses of
      the obtained results revealed some trends described below. 1. Methicillin
      resistant Staphylococcus aureus (MRSA), multiple drug resistant Coagulase
      negative staphylococci (CNS) and multiple drug resistant Proteus spp. showed a
      year to year trend toward a steady increasing. Relative frequencies of occurrence
      of MRSA in these years, however, remained comparable to that of early 1980's. 2.
      A year to year trend toward increasing was also found for resistant or
      insensitive Streptococcus pneumoniae to penicillins and cephems. 3. Multiple drug
      resistant Pseudomonas aeruginosa strains were also detected but they showed no
      trend toward increasing.

PMID- 8254888
TI  - [Antimicrobial activity of cefodizime against fresh clinical isolates].
AB  - In order evaluate antimicrobial activities of cefodizime (CDZM), minimum
      inhibitory concentrations (MIC's) of CDZM and other control drugs were determined
      against various clinical isolates, that were sent to our center from nation-wide
      medical institutions or were isolated and identified in our laboratory from
      various specimens of infected patients. The followings are a summary of the
      results: 1. Bacterial species with no or few strains resistant to cephems
      including CDZM included Streptococcus pyogenes, Haemophilus influenzae,
      Citrobacter diversus, most of Klebsiella pneumoniae and Proteus mirabilis. Some
      strains of Klebsiella oxytoca were resistant to cephems increases in beta-lactams
      resistant Streptococcus pneumoniae and cephem resistant Escherichia coli seemed
      likely. Among Citrobacter freundii, Enterobacter spp., Serratia marcescens,
      Proteus vulgaris, Morganella morganii and Providencia spp. belonging to a
      category of so-called "mildly toxic bacteria", high portions of the strains
      examined were resistant to cephems including CDZM and these strains were also
      resistant to new quinolones, thus they showed multiple drug resistance. 2.
      MIC90's of CDZM against Streptococcus spp., H. infleunzae, Moraxella subgenus
      Branhamella catarrhalis, E. coli, Klebsiella spp. and P. mirabilis, frequently
      found in daily treatment of infections, were less than < or = 0.025 to 1.56
      micrograms/ml. This indicates that CDZM would be expected to have enough
      antibiotic activity in infections caused by above mentioned bacteria. However,
      cautions are needed in the treatment of infections by beta-lactam resistant S.
      pneumoniae, cephem resistant E. coli and cephem resistant K. oxytoca with CDZM.
      3. Among the above mentioned "mildly toxic bacteria", many multiple drug
      resistant strains exist. Therefore, we evaluated an usefulness of concomitant use
      of CDZM with aminoglycosides in the treatment of infections by these bacteria,
      using other reports which indicates the usefulness in vitro and in vivo. 4.
      Antibacterial activities of CDZM we observed in this study seem to indicate that
      CDZM concentrations in infected areas are maintained at above MIC levels for
      relatively long periods of time.

PMID- 8254889
TI  - The antimicrobial activity in vitro of cefpirome and 6 other beta-lactam
      antibacterial agents against clinical isolates.
AB  - The in vitro activity of cefpirome (CPR) was compared with that of cefazolin
      (CEZ), cefotiam (CTM), flomoxef (FMOX), cefotaxime (CTX), ceftazidime (CAZ) and
      imipenem/cilastatin (IPM/CS) against 384 clinical isolates, for tested by the
      both microdilution method. The activity of CPR against Staphylococcus aureus
      (MIC50, 1 microgram/ml) and Enterococcus faecalis (MIC50, 8 micrograms/ml) was
      better than CTX and CAZ, but slightly less than IPM/CS. CPR and other
      antibacterial agents were not effect against methicillin resistant S. aureus and
      Enterococcus faecium. The activity of CPR against Enterobacteriaceae was as good
      as that of CTX, CAZ, and IPM/CS, and more effective than CEZ, CTM and FMOX. The
      MIC50 of CPR for Acinetobacter calcoaceticus (2 micrograms/ml) and the MIC50 of
      CPR for Pseudomonas aeruginosa (8 micrograms/ml) were as good as that of CAZ.
      Conclusionly, CPR was a new broad spectrum cephalosporin as compared with used
      cephalosporins.

PMID- 8254890
TI  - [Antimicrobial activities of polymyxin B against clinically isolated microbial
      strains. Results of MIC determination including high concentrations].
AB  - Minimum inhibitory concentrations (MICs) were determined for polymyxin B (PL-B),
      gentamicin, ofloxacin and norfloxacin against clinically isolated microbial
      strains collected since November 1992, and the following conclusions were
      obtained: 1. Judging from the MIC distribution of PL-B against the studied
      strains including multi-drug resistant organisms of major strains of family
      Enterobacteriaceae, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter
      spp., and Pseudomonas aeruginosa, it appeared that no PL-B resistant strains were
      detected among those Gram-negative organisms within the antimicrobial spectrum of
      PL-B. 2. MICs of PL-B against most strains including methicillin resistant
      Staphylococcus aureus and coagulase-negative staphylococci were distributed
      between 100 and 800 micrograms/ml. These results supported reports of other
      investigators that the eradication of Staphylococcus spp. including MRSA
      (methicillin-resistant S. aureus) was possible by the use of PL-B at 1 mg/ml. 3.
      MIC distribution of PL-B against organisms of the Bacteroides fragilis group was
      almost the same as the results described above.

PMID- 8254891
TI  - [Therapeutic efficacies of neticonazole (SS717) cream and solution in
      experimental cutaneous Candida albicans infection of guinea pigs].
AB  - The therapeutic efficacies of 1% neticonazole (SS717) cream and solution on
      experimental cutaneous Candida albicans infection produced in prednisolone
      treated guinea pigs were compared with those of 1% bifonazole (BFZ). Active
      preparations or blank vehicles were applied once daily for 3 consecutive days
      starting 5 days postinfection. Therapeutic effects were assessed on the basis of
      viable counts recovered from the infected loci 9 days postinfection. In animals
      treated with SS 717 or BFZ cream, a significant mycological improvement was
      observed when compared to untreated controls. A significant therapeutic efficacy
      of a SS717 cream compared to cream vehicle was also noted, while there was no
      significant difference in the recovery of Candida between the untreated control
      group and the cream vehicle-treated groups. The mycological result of the SS717
      solution treated group was significantly superior to those of the untreated
      control group, the solution vehicle-treated group and the BFZ solution-treated
      group. The treatment with a solution vehicle or a BFZ solution appeared to lower,
      though not to a significant level, viable counts at the infected loci. These
      results led us to the conclusion that both SS717 cream and solution preparations
      exhibited significantly superior activity to that of BFZ in experimental
      cutaneous candidasis of guinea pigs.

PMID- 8254892
TI  - [Efficacy of fluconazole on systemic mycosis associated with hematologic
      malignancies and a study on diagnostic value of plasma beta-D-glucan levels].
AB  - Efficacy of fluconazole (FLCZ), an anti-fungal agent of triazole derivatives, was
      evaluated in patients with systemic mycoses and suspected mycoses associated with
      hematologic malignancies including leukemia, myelodysplastic syndrome and
      malignant lymphoma. Plasma beta-D-glycan levels, the differences between the
      levels determined toxicolor test and in endospecy test, were also investigated.
      Fourteen patients with systemic mycoses and 31 patients with suspected mycotic
      infections were treated with intravenous administration of FLCZ at a daily dose
      of 400 mg. Excellent to good responses were observed in 4 of the 14 patients
      (28.6%) with definitive diagnosis of mycosis, and in 18 of the 31 patients
      (58.1%) with suspected fungal infections, with an overall efficacy rate of 48.9%
      (22/45). Levels of plasma beta-D-glycan correlated well with efficacies of FLCZ
      in 19 of 30 patients. In several cases, however, plasma beta-D-glucan levels were
      low during the entire course of treatment. Even in 10 cases of definite mycosis,
      4 cases showed low levels of plasma beta-D-glucan (below 15 pg/ml by repeated
      determinations). The results indicate that FLCZ is an effective agent for the
      treatment of severe systemic fungal infections in patients with hematologic
      disorders. Deep seated mycosis cannot be ruled out even when its plasma levels of
      beta-D-glucan are low.

PMID- 8254893
TI  - [Clinical evaluation of combination therapy with sulbactam/cefoperazone and
      amikacin sulfate for infections associated with hematological disorders].
AB  - We evaluated the efficacy and safety of combination therapy with
      sulbactam/cefoperazone (SBT/CPZ) and amikacin sulfate (AMK) in severe infections
      associated with hematological disorders. The clinical efficacy rate in 82
      evaluable patients was 70.7%. The efficacy rate in sepsis from which causative
      organisms were isolated was high, 75% (3/4). No significant difference was found
      between those cases for which no previous antibiotic therapies were made and
      those for which antibiotic therapies were done and changed to the combination
      during the course of the therapies. No side effects nor substantial abnormal
      laboratory test results attributable to the test drugs were observed. From these
      observations, we have concluded that the combination therapy with SBT/CPZ plus
      AMK is a very useful empiric therapy for severe infections associated with
      hematological disorders.

PMID- 8254894
TI  - [Multicenter study of the effects of sulbactam/cefoperazone on bacterial
      infections in the fields of internal medicine focused mainly on respiratory
      infections in Tochigi Prefecture].
AB  - Clinical effects of sulbactam/cefoperazone (SBT/CPZ) was studied on variety of
      bacterial infections in the fields of internal medicine focused mainly on
      respiratory infections. The total 135 infections were consisted of 103
      respiratory infections, 15 urinary tract infections, 4 sepsis, 7 biliary tract
      infections, and 6 other infections, of which 86 patients had underlying diseases.
      The daily doses of SBT/CPZ were 2 to 6 g divided into 2 to 3 times i.v. or
      d.i.v., and the duration of administration was from 3 to 35 days. The clinical
      effects were judged by the attending doctors based on the changes in fever,
      cough, rales, chest rentogenograms, white blood cell counts, CRP values, ESR,
      etc. The total efficacy rate was 76.9%, and 69.0% of the isolated organism was
      eradicated by SBT/CPZ. The side effect was noted in 1 case, and the abnormal
      laboratory findings were noted in 1 case, however it was difficult to determine
      whether they were due to SBT/CPZ. These results suggest that the clinical
      usefulness of SBT/CPZ for the infections in the fields of internal medicine.

PMID- 8254895
TI  - [Effect of cefditoren pivoxil on carnitine metabolism in pediatric patients].
AB  - Carnitine metabolism was studied in 16 pediatric patients with various infections
      under the treatment with cefditoren pivoxil (CDTR-PI) in granular form. Pivalic
      acid released from pivaloyloxymethyl ester of the drug was metabolized to
      pivaloylcarnitine. As results, an increase in urinary carnitine excretion
      (predominantly as pivaloylcarnitine) and, a decrease in free carnitine
      concentration and a high acyl/free carnitine ratio in serum (plasma) were
      observed during the treatment. When the dosing was terminated, pivaloylcarnitine
      in plasma and then in urine disappeared, and the concentration of free carnitine,
      acyl/free carnitine ratio returned to the normal range. No carnitine-related side
      effects were observed throughout the study.

PMID- 8254896
TI  - [(New antimicrobial agent series XLIV): cefpodoxime proxetil].

PMID- 8254897
TI  - [In vitro antifungal activity of omoconazole nitrate, a new imidazole
      antimycotic].
AB  - In vitro antifungal activities of omoconazole nitrate (OMZ), a new topical
      imidazole antifungal agent, were studied against 364 strains of 22 genera and 47
      species of stock cultures of a wide range of medically important fungi. The test
      was carried out using the agar dilution method with bifonazole (BFZ) as the
      reference drug. OMZ exhibited a broad spectrum of antifungal activities. Most of
      yeasts including Malassezia, dimorphic fungi, non-pigmented hyphomycetes and
      dermatophytes were almost equally or more greatly susceptible to OMZ than to BFZ,
      although the MIC values of these drugs against Candida and probably some other
      fungi were influenced differently by testing media. Comparable susceptibility to
      OMZ were observed for fresh clinical isolates of dermatophytes and Candida
      albicans. OMZ was also active against Malassezia. These results have encouraged
      us to proceed in vivo studies using animal models of cutaneous mycoses.

PMID- 8254898
TI  - [Antimicrobial activities of sultamicillin against clinical isolates obtained
      from outpatients].
AB  - Minimum inhibitory concentrations (MICs) were determined for sultamicillin
      (SBTPC), and for other major oral beta-lactam agents against clinically isolated
      strains collected from outpatients during a period from August, 1992 to February,
      1993, and the following conclusions were obtained. 1. The ratio of penicillinase
      (PCase)-producing strains of Staphylococcus aureus was 96.0% and that of
      methicillin-resistant S. aureus (MRSA) was 12.0%. MIC90 of SBTPC against S.
      aureus including MRSA was 6.25 micrograms/ml. No increasing tendency was observed
      for S. aureus resistant to SBTPC. 2. No resistant strains were found among
      Streptococcus pyogenes and Enterococcus faecalis against penicillins (PCs)
      including SBTPC. But PCs and cephems (CEPs) insensitive or resistant
      Streptococcus pneumoniae were observed in 22.0% among all the strains of S.
      pneumoniae. 3. 100% of the tested both strains of Escherichia coli and Proteus
      mirabilis were beta-lactamase producers. 12.0% of the tested strains of
      Haemophilus influenzae and 16.0% of the strains of Neisseria gonorrhoeae were
      also beta-lactamase producers. SBTPC showed strong antimicrobial activity against
      most of these beta-lactamase producing strains. However, in our study of beta
      lactamase productivity using plural substrates and test methods, it appeared that
      a part of strains of E. coli might produce beta-lactamase of "Extended broad
      spectrum". MICs of SBTPC and CEPs against those strains were distributed rather
      in a high range. 4. The results of the study suggested that the resistant strains
      of S. pneumoniae against PCs and CEPs might be increasing year by year. Some of
      strains of E. coli, resistance against the 2 agents were observed. It is
      important to keep observing changes in resistance of such organisms in the
      future. 5. The antimicrobial activities of SBTPC against clinically isolated
      strains in this study indicated potential problems such as those mentioned above.
      It is, however, also confirmed that SBTPC shows still strong antimicrobial
      activities against most of beta-lactamase producing strains found in daily
      medical examinations. Taking into consideration of the strong activities of SBTPC
      against so-called indirect pathogenicity caused by beta-lactamase producing
      indigenous bacteria reported lately, SBTPC may be a useful antibiotic for
      community acquired infections in the 1990's.

PMID- 8254899
TI  - [Antimicrobial activities of arbekacin against methicillin-resistant
      Staphylococcus aureus isolated from patients of a pediatrics ward].
AB  - Aiming at measuring the antimicrobial activities of arbekacin (ABK) against the
      strains of methicillin-resistant Staphylococcus aureus (MRSA), isolated from
      pediatrics patients in 1992, the minimum inhibitory concentration (MIC) of 8
      antibiotics including ABK was determined and the coagulase types of those strains
      were also examined. The obtained results are summarized as follows. 1. Among
      coagulase types of a total of 78 strains, Type II, Type IV and Type VII were
      84.6%, 12.8% and 2.6%, respectively. No clear difference in coagulase types were
      observed among their origins of isolation. 2. MIC90 of ABK against 42 strains
      isolated from the air passage of suspected pneumoniae patients and 36 strains
      isolated from the blood of suspected septicemia patients were 1.56 micrograms/ml
      and 3.13 micrograms/ml, respectively, and MIC90 of ABK against the 78 strains was
      1.56 micrograms/ml, which was equal to that of vancomycin (VCM). 3. Most of these
      strains exhibited resistance against multiple antibiotic agents including
      cefmetazole (CMZ), imipenem (IPM), fosfomycin (FOM) and minocycline. Strains
      isolated from the blood were mostly resistant to multiple agents, and most of
      them were especially highly resistant to CMZ and IPM. ABK, however, showed potent
      antimicrobial activities even to those strains. These results were similar to the
      results obtained several years ago. 4. Considering the fact that ABK demonstrates
      not only potent antimicrobial activities against MRSAs isolated from the
      pediatric patients, but also shows remarkable clinical effects with concomitant
      use with beta-lactams or FOM, the prospect of ABK use in MRSA infectious diseases
      of children is excellent.

PMID- 8254900
TI  - [The antimicrobial activity of cefteram against recently clinically detected and
      isolated strains].
AB  - In order to examine antibiotic activities of cefteram (CFTM), its minimum
      inhibitory concentrations (MIC's) and those of other cephem drugs were determined
      against clinically isolated strains received from July 1990 to June 1991 and from
      July 1992 to February 1993 from medical facilities throughout the country and
      against clinically isolated strains detected in our laboratory in samples from
      patients with various infectious diseases. The obtained results are summarized
      below. 1. No CFTM-resistant strains were found among beta-streptococci,
      Klebsiella spp., Proteus mirabilis, Haemophilus influenzae, and Neisseria
      gonorrhoeae or even when found, they were present in extremely low proportions.
      2. It appeared that Streptococcus pneumoniae insensitive or resistant to beta
      lactams, as well as cephems-resistant strains of Escherichia coli were
      increasing. The former included benzylpenicillin (PCG)-insensitive S. pneumoniae
      (PISP) of PCG-resistant S. pneumoniae (PRSP), and the presence of the latter
      suggests the possibility of the existence of "Extended broad-spectrum beta
      lactamase" producing strains. The MIC's of beta-lactams against the above PISP or
      PRSP, and against cephems-resistant E. coli tended to be high, but those of CFTM
      were relatively low (in most cases). 3. Proportions of strains resistant to
      cephems, including CFTM among Citrobacter spp., Enterobacter spp., Serratia
      marcescens, Proteus vulgaris, Morganella morganii, and Providencia rettgeri were
      high, and in addition, the existence of these cephem resistant species suggests
      an increase in multiple drug resistant strains that show resistance to new
      quinolone drugs. 4. As mentioned above, CFTM is by no means a perfect drug or
      utility drug and its antimicrobial activities do not cover some recent isolates
      with multiple drug resistance. Except problems encountered with so-called
      "attenuated" strains of bacteria, increases in resistance can only be observed at
      a level of MIC90's, and as far as MIC80's are concerned, CFTM still is as active
      as before and may be used in the treatment of most infections we encounter in
      normal medical practices.

PMID- 8254901
TI  - [Reaction mechanism of macrolide 2'-phosphotransferase from Escherichia coli to
      the 2'-modified macrolide antibiotics].
AB  - Reaction mechanism of macrolide 2'-phosphotransferase [MPH(2')] from Escherichia
      coli to the 2'-modified macrolide antibiotics was analyzed by using
      microbioassay, nuclear magnetic resonance (NMR) spectrometric assay and mass
      spectrometry. It was found by microbioassay that the 2'-modified macrolide
      antibiotics as triacetyloleandomycin (TAO), erythromycin ethyl succinate (EME)
      and erythromycin estolate were inactivated with adenosine triphosphate (ATP) by
      MPH(2'). The NMR spectrometric assay for the analysis of the reaction with the 2'
      modified macrolide antibiotics and MPH(2') was established using guanosine
      triphosphate, which was higher reaction rate than ATP, as a cofactor. It was
      clearly shown by NMR spectrometric assay and mass spectrometry that the C2'-side
      chain of TAO and EME was naturally released in phosphate buffer solution, and
      then, the C2' position was phosphorylated with GTP by MPH(2').

PMID- 8254902
TI  - [A clinical study on the efficacy of ceftazidime alone or in combination with
      aspoxicillin against infections in obstetric and gynecological patients].
AB  - We studied clinical effects of ceftazidime (CAZ) alone or in combination with
      aspoxicillin (ASPC) against various infections in obstetric and gynecological
      patients. 1. Obstetric and gynecological patients (n = 91) with various
      infectious diseases were treated with CAZ alone (1-2 g x 2/day, n = 54) or in
      combination with ASPC (1-2 g x 2/day, n = 37) administered via drip infusion. 2.
      CAZ alone or in combination with ASPC was efficacious in 50 out of 54 (92.6%) or
      33 out of 36 (91.7%) patients, respectively. Overall, the efficacy ratios were
      46/49 (93.9%) against gynecological infections, 21/25 (84.0%) against perinatal
      infections and 16/16 (100%) against other infections. The bacteriological
      efficacy ratio was 21/21 (100%) while clinical effectiveness in cases in which
      causative agents were known was observed in 20 out of 21 (95.2%) patients. In
      patients who had not respond to other treatments, CAZ alone, and in combination
      with ASPC were effective in 15 out of 16 (93.8%) and 6 out of 8 (75.0%) patients,
      respectively, hence the overall efficacy ratio was 21/24 (87.5%). 3. Abnormal
      values in clinical laboratory tests were obtained in 3 out of 91 (3.3%) patients.
      No other adverse side effects were observed in any of the patients.

PMID- 8254903
TI  - Possible usefulness of cephem antibiotics with anti-staphylococcal activity for
      preventing the spread of methicillin-resistant Staphylococcus aureus.
AB  - The validity of clinical use of cephem antibiotics for preventing the spread of
      methicillin-resistant Staphylococcus aureus (MRSA) was investigated using a
      methicillin-susceptible S. aureus (MSSA) carrying mecA gene. It became evident
      that drug with anti-staphylococcal activity, such as cefuzonam (CZON) or
      cefazolin (CEZ), has comparatively low selectivity of high-level methicillin
      resistant clones (methicillin MIC range from 25 to 800 micrograms/ml) from MSSA
      carrying mecA gene among cephem antibiotics tested. At concentrations over 1.56
      micrograms/ml of both CZON and CEZ, about a 2-3 log10 decrease in viable count
      was observed. Therefore, it seems that much satisfactory disappearance of
      bacterial cells can be obtained in cooperation with host defence mechanisms.

PMID- 8254904
TI  - [A study of hypoplastic myelodysplastic syndrome].
AB  - To distinguish hypoplastic myelodysplastic syndrome (MDS) from aplastic anemia
      (AA), morphological abnormalities of bone marrow hematopoietic cells in 8
      patients with MDS and 39 patients with AA were studied. All the patients with MDS
      and AA showed prolonged plasma iron disappearance time, (PIDT1/2) > 120 min. Five
      hundred erythroid and myeloid cells, as well as 20 megakaryocytes were counted.
      Dysplastic changes were defined if morphological changes were present in more
      than 1.0% cells with only one lineage, or in more than 0.6% cells with more than
      two lineages. Twenty six of 39 patients with AA showed morphological
      abnormalities. In MDS cases, morphological abnormalities were prominent in
      trilineage cells in some cases, in bilineage (erythroid and megakaryocytic or
      myeloid and megakaryocytic cells), in others, or solely in myeloid cells or in
      megakaryocytic cells in other cases. Morphological abnormalities seen solely in
      erythroid cells, especially those with segmented nuclei were considered to be
      less significant for the diagnosis of MDS. The findings were considered to be
      useful to distinguish hypoplastic MDS from AA.

PMID- 8254905
TI  - [Cytomegalovirus antigenemia in the differential diagnosis of pulmonary
      infiltrates after allogeneic bone marrow transplantation].
AB  - For the differential diagnosis of pulmonary infiltrates after bone marrow
      transplantation, cytomegalovirus (CMV) antigenemia was evaluated in 9 episodes of
      pneumonia which developed in 7 allogeneic marrow transplant patients between 9
      and 495 days after transplant. The diagnosis of lung infiltration was made based
      on clinical findings including histological, cytological or microbiological
      examinations using bronchoalveolar lavage fluid specimens, sputum or lung tissue.
      The CMV antigen-positive leukocytes were detected with a direct immunoperoxidase
      technique using a peroxidase-labeled monoclonal antibody (HRP-C7) against CMV
      immediate early antigen. The episodes included 2 CMV pneumonias, 1 pneumocystis
      carinii pneumonia, 1 adenovirus pneumonia, 1 bacterial pneumonia, 1 bacterial and
      fungal pneumonia, 2 idiopathic pneumonias and 1 capillary leak syndrome
      associated with hyper acute GVHD. The CMV antigenemia became positive only in two
      patients with CMV pneumonia and the number of CMV antigen-positive leukocytes
      exceeded 10 per 50000 WBCs. The CMV antigenemia test required only 24 hours to
      obtain results. These observations suggest that the detection of CMV antigenemia
      is of great value in the differential diagnosis of pulmonary infiltrates in
      marrow transplant patients.

PMID- 8254906
TI  - [Idiopathic thrombocytopenic purpura in childhood: retrospective analysis of the
      clinical prognosis].
AB  - To evaluate the relationship between initial therapy and clinical prognosis,
      retrospective analyses were performed in 73 children with idiopathic
      thrombocytopenic purpura treated in our hospital during the past 12 years. The
      patients were classified into three groups as follows: group A, 34 patients
      recovered from thrombocytopenia within six weeks after onset; group B, 9 patients
      recovered in a period of six weeks to six months; group C, 30 patients remained
      thrombocytopenia beyond six months. The majority of the patients in group A (82%)
      and group B (56%) provided a history of some infection within the preceding three
      weeks. The patients in group A and group B had epistaxis or purpura of mucous
      membranes more frequently than the patients in group C. Although, in group A and
      group B, steroid therapy and intravenous high-dose immunoglobulin (IVIG) therapy
      has been shown to rapidly increase platelet counts, many patients had become
      thrombocytopenia again from ten days after starting treatment. Therefore, there
      was no evidence that steroid therapy and IVIG therapy could reduce a total period
      of the thrombocytopenia compared with no treatment. The evidence suggested that
      those therapies, steroid therapy and IVIG therapy, might have influenced the
      essential natural history of the condition. The mean platelet associated IgG
      values in group C was significantly greater than in group A and group B with the
      platelet counts exceeds 100,000/microliters.

PMID- 8254907
TI  - [Acute progressive polyneuropathy in a patient with Waldenstrom
      macroglobulinemia].
AB  - A case of Waldenstrom's macroglobulinemia (WM) (IgM-kappa type) associated with
      acute-onset demyelinating peripheral neuropathy is reported. A 49-year-old woman
      was admitted to our hospital because of general fatigue and recurrent syncope
      attacks. She was treated with vincristine, cyclophosphamide, epirubicin and
      prednisolone. By 10th hospital day, her clinical condition improved and serum
      viscosity was reduced. However, on the 21st hospital day, she suffered from
      rapidly progressive writing and gait disturbance. Neurological examination showed
      muscular atrophy and weakness in the distal part of four extremities. Deep tendon
      reflexes were diminished. There was no sensory deficit. Cerebrospinal fluid was
      normal. Anti-myelin associated glycoprotein activity of her serum was negative.
      Both motor and sensory nerve conduction velocities were markedly decreased.
      Biopsy of sural nerve revealed marked demyelination and onion bulb formation.
      There was IgM deposition on myelin sheath. Minimal axonal changes excluded the
      possibility of vincristine neuropathy. Plasmapheresis improved her symptoms, but
      nerve conduction velocities remained unchanged. Polyneuropathy associated with WM
      is usually gradual onset and sensory dominant. In this case, associated
      neuropathy was acute onset, progressive and motor dominant. This type of
      neuropathy in patients with WM is very rare.

PMID- 8254908
TI  - [RAEB transformed into AML (M0) showing Ph1 chromosome and rearrangement of major
      cluster region].
AB  - A 78 year old female was found to have pancytopenia in February 1991. Bone marrow
      was normocellular with 11.7% blasts and showed dysmegakaryopoietic changes. A
      diagnosis of MDS (RAEB) was made and she was treated with transfusions and
      ubenimex. Leukemic transformation was noted in July. On Admission in October
      1991, her laboratory examinations revealed the following: WBC 38,900/microliters
      with 93% blast, Hb 8.0 g/dl, Plt 2.1 x 10(4)/microliters, a hypercellular bone
      marrow with 74% blasts which were negative for myeloperoxidase (MPO) by light
      microscopy, but were positive by electron microscopy. Surface marker for CD13 was
      positive. These findings corresponded to M0 of the FAB subtype. Chromosome
      analysis revealed Ph1 chromosome with 46XX, t (9;22) (q34;q11) in 3 of 3 cells
      examined, Southern analysis showed the rearrangement of the break point cluster
      region (bcr). Reverse transcriptase polymerase chain reaction technique
      demonstrated the presence of major bcr/abl mRNA. She was treated with
      transfusions and methyl-prednisolone. Her blast counts declined and Ph1
      chromosome was only positive in 1 of 12 metaphases examined. She died of
      pneumonia in December 1991. Eleven cases with MDS showing Ph1 chromosome have
      previously been reported. The observations indicate that Ph1 chromosome positive
      acute leukemias were heterogenous in nature.

PMID- 8254909
TI  - [Successful treatment by ranimustine (MCNU) of a patient with B-cell
      prolymphocytic leukemia (B-PLL)].
AB  - A 66-year-old female was admitted to our hospital because of leukocytosis, anemia
      and splenomegaly in August 1989. The white cell count was 3.49 x 10(10)/l with
      88.5% of the leukemic cells which were morphologically similar to prolymphocytes.
      On flowcytometric analysis, the leukemic cells were found to be positive for B
      cell markers such as CD19, CD20, FMC7, Sm-IgM and Sm-IgD and negative for CD5 and
      CD25. The chromosome analysis demonstrated hyperdiploidy of 48, XX, (+3, +18).
      She was diagnosed as having B-cell prolymphocytic leukemia, and treated with
      alpha-interferon and VP therapy with progression. Complete remission was achieved
      after three courses of ranimustine (MCNU) administration. She relapsed after
      about one year without therapy, but when MCNU was administered again, a secondary
      remission followed. The prolymphocytes during the relapse stage also had the
      phenotypes of CD11b, CD13 and CD25. This case is considered to be rare with
      respect to both complete remission by MCNU and the immunophenotypic change of
      leukemic cells during the relapse period.

PMID- 8254910
TI  - [Renal plasmacytoma].
AB  - Extramedullary plasmacytoma arising in the kidney is uncommon. So far only 11
      cases have been reported. Recently, we noted the 12th case, the third case seen
      at the Kyoto University Hospital. The literature is reviewed. A 43-year-old man
      was hospitalized because of paraplegia due to spinal cord compression by the
      solitary plasmacytoma arising in the cervical spine, producing an IgG-lambda
      paraprotein. The tumor excision was followed by radiotherapy and standard
      chemotherapy. Two years later, new lesions on the thoracic spine, the left
      clavicle, and the occipital bone successively developed with Bence Jones
      proteinuria (lambda), but without IgG-lambda paraproteinemia. Ga-67 scanning was
      performed to detect extramedullary tumors. The marked accumulation of the
      radionuclide revealed intraabdominal tumors. A CT scan of the abdomen revealed a
      large soft-tissue mass (73 x 50 mm) emanating from the right kidney and several
      enlarged lymph nodes. Ultrasound of the right kidney revealed a solid mass with
      hydronephrotic change. RI-renogram showed delayed excretion from the right
      kidney. Clusters of myeloma cells were repeatedly observed in the urinary
      sediment. Thus, a diagnosis of plasmacytoma of the kidney was made. Treatment
      with radiotherapy alone was sufficient.

PMID- 8254911
TI  - [Pure red cell aplasia complicated with polyarthritis, angitis, and acute renal
      failure].
AB  - A case of pure red cell aplasia (PRCA) with various complications polyarthritis,
      angitis, acute renal failure and DIC was successfully treated with steroid pulse
      therapy was described. A 55-year-old woman was hospitalized with a 9-month of
      intermittent but progressive joint pain, morning stiffness, general fatigue, and
      fever. Her initial laboratory evaluation revealed a hemoglobin of 4.4 g/dl and
      absence of reticulocyte. Her bone marrow aspirate showed no erythroblast which
      was compatible with a diagnosis of PRCA. Marked leukocytosis and thrombocytosis,
      positive antinuclear antigen, elevation of gammaglobulin and C-reactive protein
      and the presence of polyarthritis and angitis which was confirmed by renal
      angiography, indicated an underlying autoimmune disorders. Steroid pulse therapy
      was administered at 500 mg/day for 3 days, resulting in the complete response in
      both red cell aplasia and above findings. PRCA is known to be associated with
      systemic lupus erythematosus and rheumatoid arthritis very rarely, but this case
      did not fulfill the criteria of known collagen diseases, and there is no previous
      report representing PRCA with various complications such as polyarthritis,
      angitis and acute renal failure. This case may help us to understand more about
      the relationship between PRCA and autoimmune disorders.

PMID- 8254912
TI  - [Hemophilia A complicated with hepatocellular carcinoma].
AB  - A 60-year-old hemophiliac man complaining of abdominal discomfort was admitted on
      suspicion of hepatocellular carcinoma (HCC) by ultrasonography (US). When he was
      22-year-old, blood transfusion was given for intra-abdominal hematoma due to an
      external wound and a diagnosis of moderate hemophilia A and non-A non-B type
      chronic hepatitis (later, C type chronic hepatitis) was made at the age of 40.
      After admission, HCC in the S6 segment of the liver was diagnosed by US,
      computerized tomography, magnetic resonance imaging and angiography. He was
      treated with transcatheter arterial embolization (TAE) and partial resection of
      the liver. Later, percutaneous ethanol injection therapy and TAE was performed
      because of the recurrence of HCC. He is now alive with no evidence of recurrence.
      The rate of infection with hepatitis C virus (HCV) is significantly high in
      hemophiliacs but, because of the replacement therapy, their life expectation has
      dramatically improved in last two decades. Therefore, it is speculated that the
      incidence of HCC in hemophiliacs will increase. We emphasize that regular US
      examination for HCV-positive hemophiliacs is important for the early detection of
      HCC.

PMID- 8254913
TI  - [Changes of bone marrow MRI pattern in aplastic anemia before and after bone
      marrow transplantation].
AB  - In order to evaluate the usefulness of magnetic resonance imaging (MRI) in
      estimating bone marrow cellularity, we performed T1-weighted MRI of the lumbar
      vertebral marrow in two patients with severe aplastic anemia, before and after
      bone marrow transplantation (BMT). High signal intensity was detected in the bone
      marrow before BMT, but the bone marrow pattern of MRI became normal after BMT.
      MRI seems to be effective for evaluating bone marrow cellularity and recovery,
      and for monitoring therapeutic effects in patients with aplastic anemia before
      and after treatment with BMT.

PMID- 8254914
TI  - [Multiple myeloma associated with diffuse parenchymal amyloidosis of the lung].
AB  - A 58-year-old woman was hospitalized in March, 1991, with slight breathlessness
      on exertion. Laboratory investigations revealed M-protein (IgG lambda type,
      7,575mg/dl) in serum, and Bence-Jones proteinuria. Osteolytic bone lesions were
      noted roentgeno-logically. Bone marrow aspiration showed the presence of 19% of
      atypical plasma cells, and the case was diagnosed as multiple myeloma. The chest
      X-ray film showed bilateral diffuse micronodules, which were found by a
      transbronchial lung biopsy to be diffuse parenchymal amyloid deposits. The
      patient was treated with melphalan, prednisolone and interferon-alpha for 6
      courses. Clinical symptoms improved but no decrease of the level of M-protein was
      observed. The patient is still alive without changes of pulmonary shadows on X
      ray films for the past 2 years.

PMID- 8254915
TI  - [Morphology and electron microscopic structures of pituitary gland].
AB  - This article describes and illustrates a brief summary of the electron
      microscopic features of the cell types in the anterior pituitary gland on recent
      works done on animals or man. Fundamentally, the shape and size of secretory
      granules in the anterior pituitary cells are still available for functional cell
      classification today, but the morphology of secretory granules is not homogeneous
      even in single cells and various depend on different kinds of animals or man. In
      addition, co-localization of two or more hormones or peptide (s) has been
      observed in some single cells. Consequently, the "one cell-one hormone" concept
      has been fully withdrawn and more reasonable cell classification of anterior
      pituitary cells will be revised in the near future.

PMID- 8254916
TI  - [Immunohistochemistry of pituitary gland cells].
AB  - Immunohistochemistry is a very useful method for identifying the hormone produced
      in the acinar cells of the pituitary gland. The recent technical progress of the
      method have let it more popular and easy for many researchers, however, some
      basic points of the method have become to be missed on the contrary.
      Immunohistochemical results only show the fact that the immunoreactivity to the
      antibody remains in the examined tissue, but not the conclusion that the tissue
      produces hormone A. Some processes are needed in leading the latter conclusion
      from the former fact. Some necessary points in the process of the
      immunohistochemistry are discussed in the paper.

PMID- 8254917
TI  - [An application of molecular cell biology to visualize and manipulate gene
      expressions of specific proteins in the neuroendocrine and pituitary systems].
AB  - Tremendous progress in molecular biology has made it possible to investigate the
      gene structure of proteins which maintain the internal environment of the living
      tissue. A wide variety of proteins is required for the diverse functions of the
      nervous and endocrine systems, because they contain a heterogeneous population of
      highly specialized cells. The proteins in the cell are all derived from specific
      genes which encode the sequences of amino acids through the process of gene
      expression. Four stages are involved in gene expression; transcription,
      processing of RNA, translation, and post-translational processing. In situ
      hybridization is a powerful technique to detect specific mRNA at the cellular
      level with microscopic resolution. Antisense method also has an impact upon gene
      expression. The basic idea of both in situ hybridization and antisense method is
      that nucleotides complementary to a specific mRNA will bind to the mRNA as a
      probe to detect its location or as an inhibitor to block processing or
      translation. In this paper, molecular cell biology, particularly in situ
      hybridization and antisense methods is described to localize the site of specific
      gene expression of biochemical messengers in the neuroendocrine and pituitary
      systems.

PMID- 8254918
TI  - [Morphological methods for analysing hormone secretory mechanism in the pituitary
      cells].
AB  - We introduce here two morphological methods of the rat anterior pituitary cells.
      In the first experiment, we showed immunofluorescence combined with a confocal
      laser scanning microscope. Distribution of actin was examined in growth-hormone
      (GH) secreting cells and folliculo-stellate cells and compared between in vivo
      and in vitro cells. In tissue, actin immunoreactivity was mainly limited near the
      plasma membrane. In cultured cells localization of actin clearly changed and the
      cells sometimes showed stress fiber-like structures in the cytoplasm. The cells
      also showed a small amount of alpha-actinin- and myosin-like immunoreactivities
      along stress fiber-like structures, which cannot be detected in the tissue cells.
      These data clearly showed differences in the localization of cytoskeletal
      proteins between in vivo and in vitro. In the second experiment, we showed
      electron microscopic analysis combined with monitoring hormone secretion in vivo.
      A catheter was inserted through the left external jugular vein into the right
      atrium of the heart. Through the catheter GH-releasing factor (GRF) and/or
      somatostatin was administered to freely-moving rats. Only about 30% of rats
      showed an increase in blood GH after GRF injection. Such responded rats were
      selected for our morphological analysis. From 5 min after GRF injection, the rats
      were infused with somatostatin or saline for 10 min. The treatment of
      somatostatin clearly diminished exocytotic figures from the plasma membrane.

PMID- 8254919
TI  - [Analytical methods at the single cell level for measuring secretory functions of
      anterior pituitary cells].
AB  - It has been shown that cells that synthesize and secrete a specific hormone
      differ quantitatively and qualitatively one another for basal and secretagogue
      induced secretion. Four analytical methods are at present available for measuring
      secretory activity of endocrine cells at the single cell level. These include the
      reverse hemolytic plaque assay, cell membrane capacitance method, quinacrine
      fluorescence method, and cell immunoblot assay (CIBA). Each method has advantages
      as well as disadvantages. The CIBA has several variants such as sequential and
      sandwich CIBAs. It is possible to determine hormone secretion repeatedly from
      single cells and to identify multihormones that are cosecreted from a cell by
      using these variants.

PMID- 8254920
TI  - [Arteries to the pituitary].
AB  - The arteries of the pituitary stalk and gland were described using our results as
      well as data obtained from the literature. There were three types of vessels to
      the pituitary from above: the superior hypophyseal artery originating from the
      internal carotid artery, the infundibular artery originating from the posterior
      communicating artery, and the prechiasmal artery from the ophthalmic artery.
      There were also three arteries from the cavernous carotid artery; the inferior
      hypophyseal artery, the capsular artery, and the artery of the inferior cavernous
      sinus. These arteries were anastomosed each other, making the rich vascular
      networks, called the "circuminfundibular anastomosis" around the pituitary stalk,
      and the "inferior hypophyseal arterial circle (or inferior capsular arterial
      rete)" in the base of the pituitary.

PMID- 8254921
TI  - [Growth factors in the pituitary gland].
AB  - There are increasing numbers of evidence that many factors, such as growth
      factors and cytokines, exist in the pituitary gland, and modulate the release of
      pituitary hormone both in vivo and in vitro. They indicate the importance of
      autocrine and paracrine control system within the pituitary gland. For instance,
      activin, a compound whose existence and nature (in contrast to the related
      protein inhibin) was not contemplated before its discovery in 1986, has been
      shown to be synthesized in gonadotrophs and to produce diverse effects on the
      anterior pituitary. We would like to introduce some recent studies on growth
      factors in the pituitary gland.

PMID- 8254922
TI  - [Immune system and hypophysis].
AB  - The immune system does not function in isolation from either nervous or endocrine
      system. Recent advances in biology have made it clear that there are many
      connections between immune system and hypothalamo-pituitary axis. Among them,
      relationship of cytokines to hypothalamus is of great interest. We reviewed
      functions of the cytokines such as interleukin, interferon and tumour necrosis
      factor. For example, IL-1 releases ACTH from the hypophysis being mediated by
      corticotropin releasing hormone in the hypothalamus. ACTH shows inhibitory effect
      on the immune system. Interferons, as well as interleukins bring fever and
      anorexia via opioid receptors in the hypothalamus. There are some evidences which
      show effect of IL-1 on the posterior hypophysis which secretes vasopressin and
      oxytocin. There are, however, many unknown mechanisms in this field. The
      resolution of the specific interactions between the immune system and the
      hypothalamo-pituitary axis is subject to further investigations.

PMID- 8254923
TI  - [Intercellular communication within the anterior pituitary].
AB  - Paracrine and autocrine interactions within the anterior pituitary have been
      studied in the last few years. The adaptation of novel methodology to the study
      of the physiology of the anterior pituitary has yielded convincing evidence for
      cell-cell communication. Another reason for expanded interest in this field is
      the discovery of a growing member of substances that likely play a role in cell
      cell communication. The various types of secretory cells within the anterior
      pituitary, gonadotroph, thyrotroph, somatotroph, lactotroph and corticotroph,
      have been addressed as sources, and then targets of intercellular factors. We
      need have more a collection of observations than a system of delineated pathways.
      Moreover, care must be exercised in interpretations of these observations.

PMID- 8254924
TI  - [Pathogenesis of pituitary tumor].
AB  - Pituitary adenoma originates from adenohypophysial cells producing various
      pituitary hormones. Some of pituitary adenomas are associated with pathological
      states including primary hypothyroidism, Nelson's syndrome, hypothalamic hormone
      producing tumors, multiple endocrine neoplasia type 1, McCune-Albright syndrome
      and transgenic animals transfected with hypothalamic hormones (HP). These facts
      suggest that excessive secretion of HP induces hyperplasia of the
      adenohypophysial cells, leading to adenoma by additive effects of other unknown
      factors. The majority of the pituitary adenomas are associated with de novo
      genetic changes in the adenohypophysial cells, which induce growth factor
      independent proliferation and clonal expansion of the tumor cells, due to
      mutation of Gsa gene, activation of hst gene, expression of growth factors (HP,
      AT II, bFGF), loss of heterozygosity or loss of imprinting.

PMID- 8254925
TI  - [Recent progress in experimental pituitary tumors in various animals].
AB  - This article briefly describes the recent progress and opinion on experimental
      pituitary tumors in various animals. 1) A high incidence of spontaneous pituitary
      tumor is known in Sprague-Dawley and Wistar rats. 2) Recent studies suggest that
      the pituitaries of estrogen-treated animals are not tumoral and only
      hyperplastic. 3) Salmon calcitonin injection for 6 months caused a higher
      incidence of pituitary hyperplasia or non-functioning adenoma. 4) Mice transgenic
      by hGRF shows GH-producing hyperplasia or adenoma in the pituitary. 5)
      Introduction of choleratoxin transgene into mice caused gigantism. 6) Transgenic
      mice, that develop ACTH-producing pituitary tumor, were generated by PyLT. 7)
      Mice transgenic for vasopressin-SV 40 hybrid oncogene develop tumors of the
      endocrine pancreas and the pituitary (as a model of MEN type II).

PMID- 8254926
TI  - [Biosynthesis and secretory regulation of pituitary prolactin].
AB  - We summarized recent advancements in biosynthesis and secretory regulation of
      pituitary prolactin at the cellular and molecular levels from some literatures.
      We singled out dopamine, estrogen and thyrotropin releasing hormone (TRH) from
      many factors controlling the biosynthesis and the regulation, because they are
      important, physiologically and pathologically. Dopamine exerts some effects on
      the membranes of the lactotrope inhibiting activities of cAMP,
      phosphatidylinositols and calcium ion channels. It inhibits prolactin gene
      transcription by suppressing action of the promoter region. Estrogen and TRH
      increase prolactin biosynthesis and the secretory regulation. Estrogen coupled
      with the receptors in the cytoplasma goes directly to the DNA region -1713-->
      1495 being upstream to the starting site of prolactin transcription and differing
      from the region on which dopamine acts. TRH accelerates prolactin production and
      release in such steps as transcription, stabilization of mRNA, accumulation of
      mRNA in the cytoplasma, protein synthesis and exocytosis.

PMID- 8254927
TI  - [Gonadotropes].
AB  - A pulsatile pattern of GnRH release by GnRH pulse generator in the hypothalamus
      is required for the maintenance of gonadotrope responses, Gn-subunit mRNA
      production and release of Gn. GnRH causes up-and down-regulation of GnRH
      receptors and desensitization of Gn-release. Gn-synthesis and release are
      modulated by gonadal steroid and peptide hormone through the hypothalamus and/or
      pituitary.

PMID- 8254928
TI  - [Corticotrope].
AB  - Gene structure, transcription and processing of pro-opiomelanocortin (POMC) are
      described. Some of the regulatory factors for POMC gene transcription are also
      discussed. POMC gene consists of three exons and two relatively large introns.
      The exon-1 encodes 5' untranslated region and exon-2 encodes mostly signal
      peptide and N-terminal peptide of POMC. Exon 3 encodes all of the biologically
      active peptides contained in POMC. The translation product from mRNA is
      glycosylated and processed by peptidases to generate ACTH, beta-LPH, gamma-LPH
      and beta-endorphin in the anterior pituitary. However, in the neurointermediate
      lobe of the pituitary, ACTH is further processed to alpha-MSH and corticotropin
      like intermediate peptide and beta-endorphin is processed to acetyl-beta
      endorphin.

PMID- 8254929
TI  - [Mechanism of regulation of TSH--biosynthesis and secretion].
AB  - The pituitary glycoprotein hormone, TSH, is synthesized and secreted by
      thyrotrophs in the anterior pituitary. Similarly to other pituitary
      glycoproteins, LH and FSH, it consists of two non-covalent subunits, alpha and
      beta. The alpha-subunit is common to all three hormones, while the beta-subunit
      is unique for each hormone. Both subunits are synthesized as separate peptides
      from distinct mRNA. T3 is the most important negative regulator of the TSH gene.
      The T3-T3 receptor complex binds to the specific promoter region, T3 response
      element (TRE), of its target genes and regulates the transcriptional activities.
      Although TREs have been studied in many genes, the TSH beta-TRE has not yet been
      fully identified. The mechanism how T3 suppresses TSH beta gene remains
      undetermined. Another important TSH gene regulator, TRH, is considered to
      stimulate the transcriptional activity by binding to the different promoter
      region of TSH beta gene. The interaction between TRH-response element and Pit
      1/GHF-1, the pituitary specific factor, -response element is interesting. TRH
      affects TSH glycosylation, which is important to the biological activity. TSH in
      central hypothyroid patients is known to have a lower ratio of biological per
      immunological activity. Recently, in cases with congenital isolated TSH
      deficiency, a point mutation has been identified in the CAGY region of TSH beta
      gene, which is critical for dimer formation between alpha- and TSH beta-subunits.

PMID- 8254930
TI  - [Mechanism of action of growth hormone--receptor binding and postreceptor signal
      transduction].
AB  - Recent findings concerning growth hormone-binding to its receptor and the post
      receptor signal transduction mechanism of the hormone are reviewed. Growth
      hormone receptors have recently been included in the new cytokine receptor
      superfamily. The structure of the growth hormone receptor and a sequence of the
      chemical event leading to the expression of the effect of growth hormone, on
      cellular function, proliferation and differentiation, are reviewed in relation to
      ligands for the superfamily receptors.

PMID- 8254931
TI  - [Action mechanism of pituitary hormones--receptor and signal transduction-
      prolactin].
AB  - The purification and identification of human prolactin (hPRL) had been delayed,
      compared with other pituitary hormones, until the determination of total amino
      acid sequence of hPRL in 1977. A full-length cDNA for the hPRL receptor was
      identified from hepatoma and breast cancer cell lines in 1989. Subsequent
      identification of cDNAs for PRL receptor of several species revealed that
      molecular size of PRL receptors could be classified into three forms, i.e., long,
      short and intermediate, according to the length of intracellular domain. The
      mechanism of post-receptor signal transduction has not been clarified yet.
      However, protein kinase C may be involved in this process. Further studies are
      necessary to investigate the relationship between molecular size of PRL receptor
      and postreceptor events.

PMID- 8254932
TI  - [Gonadotropin receptor system and its signal transduction pathway].
AB  - Recent advances in genetic studies have elucidated structure of gonadotropin
      receptors. This transmembrane receptor contains seven transmembrane domains and
      induces multiple biological changes in granulosa/theca cells resulting in
      follicular maturation in women. The signal transduction involves G protein
      mediated systems, cAMP mediated systems and phospholipase C systems. This paper
      reviews recent advances in gonadotropin receptor system and its signal
      transduction pathway.

PMID- 8254933
TI  - [Adrenocorticotropin receptor in familial glucocorticoid deficiency].
AB  - Recent studies have revealed the presence of four subtypes for the melanocortin
      receptor (MC-R). Among these MC-Rs, MC2-R is considered to be an
      adrenocorticotropin (ACTH) receptor because its expression is almost localized in
      the adrenal cortex. Five Japanese patients with ACTH unresponsiveness were
      examined as to whether they have mutations in the putative ACTH receptor. Among
      these patients, there are two groups of siblings, each of which consists of two
      individuals. The coding region of the ACTH receptor gene was amplified by
      polymerase chain reaction and directly sequenced on both strands, however, no
      point mutation was found in any of the five patients, suggesting that familial
      glucocorticoid deficiency, caused by the mutated ACTH receptor, may be rare.

PMID- 8254934
TI  - [TSH receptors and signal transduction].
AB  - The TSH receptors constitute one of the main part of the signal transduction in
      thyroid cells and are the main biochemical targets in pathological changes.
      Recent molecular cloning of the TSH receptor and site-directed mutagenesis
      experiments have provided new evidence. It is well-established that TSH activates
      the cAMP cascade. Recent evidence however suggests that TSH can also activate the
      PIP2 cascade, but not anti-TSH receptor antibody. Specific alpha-subunits of the
      GTP binding protein modulate the stimulation of both pathways. Moreover, the
      thyroid diseases linked to the mutation of the GTP binding protein are seen.
      Although the TSH action in thyrocytes, through both pathways, are distinct, they
      are too complicated to classify clearly. The mechanism of the TSH stimulating
      pathway and the TSH function in thyrocytes are reviewed.

PMID- 8254935
TI  - [Recent advances in vasopressin receptors and signal transduction system].
AB  - The antidiuretic hormone arginine vasopressin (AVP) receptors are G protein
      coupled and have been divided into at least three types: V1a (vascular/hepatic)
      and V1b (anterior pituitary) receptors, which act through phosphatidylinositol
      hydrolysis to mobilize intracellular Ca2+; and V2 (kidney) receptor, which is
      coupled to adenylate cyclase. Recently V1a and V2 receptor cDNAs were cloned.
      These cDNAs encode proteins with seven putative transmembrane domains and a
      similar structure to rhodopsin and other G protein-coupled receptors. Micro
      localization of mRNA coding for V1a and V2 receptors was carried out in the rat
      kidney using a reverse transcription and polymerase chain reaction. Large signals
      for V1a receptor PCR product were detected in glomerulus, cortical collecting
      duct (CCD), outer medullary collecting duct (OMCD), inner medullary collecting
      duct (IMCD), and arcuate artery. Large signals for V2 receptor PCR product were
      detected in CCD, OMCD, and IMCD. 72-hour dehydration caused decrease of V2
      receptor mRNA, but no change in V1a receptor mRNA in rat IMCD. These data show
      that mRNA coding for the two AVP receptor subtypes are distributed differently
      along the nephron and renal vascular system, and that these mRNAs are regulated
      differently in response to the dehydrated state. Recently, two reports of a
      mutation in the vasopressin V2 receptor gene in a kindred with X-rinked
      nephrogenic diabetes insipidus are published. These studies demonstrated that
      point mutation of V2 receptor gene causes the nephrogenic diabetes insipidus.
      Understanding the nature of defective diabetes insipidus may ultimately lead to
      improved therapy.

PMID- 8254936
TI  - [Imaging of the pituitary gland].
AB  - Several modalities including plain radiography, CT, and MRI are available for
      evaluation of the intrasellar, suprasellar and parasellar lesions. Plain
      radiography, which may used for screening, can identify calcification as well as
      the elusive and destructive changes of the sella turcica and it's adjacent bony
      structures. CT is much more sensitive in detecting calcifications. It is also
      useful for demonstrating bony changes in detail. MRI has been thought to be the
      best modality in evaluation of sellar and parasellar lesions. Dynamic MRI is a
      choice of method when microadenoma is suspected.

PMID- 8254937
TI  - [Measurements of serum pituitary hormones and dynamic tests to evaluate the
      pituitary functions].
AB  - Hormones produced by the anterior pituitary have conventionally been measured in
      the serum by radioimmunoassays (RIA), whereas more sensitive immunoradiometric
      assays (IRMA) have now been developed and are replacing RIA. Dynamic tests
      (stimulatory tests and suppression tests) rather than single and random
      determinations are often important tools in the study of pituitary functions.
      Stimulatory tests (such as glucagon plus propranolol test for growth hormone and
      water deprivation test for arginine-vasopressin) are used to evaluate
      hypofunction and suppression tests (such as dexamethasone suppression test for
      adrenocorticotrophic hormone) are used to investigate hyperfunction. This
      chapter, mainly dealing with representative dynamic tests, describes test
      protocols and how to interpret test results.

PMID- 8254938
TI  - [Detection methods of anti-pituitary autoantibodies].
AB  - Bottazzo et al. first reported an assay method of antibodies to human pituitary
      endocrine cells, using an indirect immunofluorescent technique in 1975. In 1986
      Sugiura et al. established a sensitive assay method for pituitary cell antibodies
      by biotin/avidin detection technique using rat pituitary. They also developed a
      sensitive assay for antibodies to anterior pituitary cell membrane by
      immunofluorescence methods using AtT-20 cells and GH3 cells. Recently Crock et
      al. reported a new approach to the detection of pituitary antibodies by
      immunoblotting. We focused on assay methods reported previously, including our
      results of pituitary antibodies in patients with autoimmune thyroid disease. The
      existence of autoimmune disorders of the pituitary is now accepted on both
      experimental and clinical grounds.

PMID- 8254939
TI  - [Recent progress in diagnosis and treatment of patients with GH deficiency and GH
      overproduction].
AB  - The diagnostic criteria of GH deficiency and acromegaly have been revised in 1990
      by the Ministry of Health and Welfare in Japan. According to this criteria, not
      only the classical type of severe GH deficiency but also partial GH deficiency
      can be diagnosed and treated. With development of technology, anatomical
      abnormalities could be seen by MRI and genetic abnormality analysed. For the
      treatment of patients with GH deficiency, the pen-system has becomes available,
      which makes the daily injection of GH painless and easy. For the treatment of GH
      producing pituitary tumor (acromegaly), a long acting analog of somatostatin is
      now available to reduce the size of the tumor.

PMID- 8254940
TI  - [Prolactin producing adenoma].
AB  - Prolactin (PRL)-secreting tumors are the most common pituitary adenomas in
      humans. Of all pituitary adenomas, PRL-secreting adenoma (prolactinoma) represent
      about 40%. It is important to point out that the definition of prolactinomas
      should include the presence of hyperprolactinemia and emphasize that
      hyperprolactinemia, especially at levels of less than 200 ng/ml, can be secondary
      to many other sellar lesions. These issues are important not only in defining the
      pathophysiology of hyperprolactinemia, but also in choosing appropriate
      treatments. Magnetic resonance (MR) imaging, especially high resolution MR
      imaging has replaced CT as the primary imaging modality for pituitary tumors.
      With contrast media microadenomas are not enhanced immediately and, therefore
      show up as areas of decreased signal intensity. MR imaging of PRL-secreting macro
      adenoma has the advantage of being able to demonstrate the relationship of the
      tumor to the optic nerve and the cavernous sinus. Therapeutic considerations
      depend on the associated symptoms and the size of the lesion on pituitary
      scanning. Surgical resection of adenomas cures in most patients with the
      disorder. The drop in serum PRL levels to very low levels immediately after
      transsphenoidal adenomectomy of PRL-secreting microadenoma followed by the
      gradual recovery of lactotroph responsiveness to stimuli over months. In case of
      macroadenoma surgical resection cures only about 50%. But surgical resection
      rapidly improves the vision, decreases the administered bromocriptine (BC) volume
      and dose not develop a leak of cerebrospinal fluid after packing of the floor ot
      the sella. Random biopsy and radical resection of diaphragma sella effectively
      elevate the curative rate, because PRL-secreting adenoma tends to
      infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254941
TI  - [Gonadotroph adenomas].
AB  - Gonadotroph adenomas have previously been considered to be a rare pituitary
      adenoma, because excessive secretion of gonadotropins does not always associate
      with its corresponding clinical syndrome. Therefore, these adenomas can be
      categorized as clinically non-functioning adenomas. However recent studies,
      including immunohistochemistry, electron microscopy, tissue culture, plaque
      assay, and in situ hybridization have classified gonadotroph adenomas may be more
      common than those it has been considered. In addition, many adenomas which
      previously have been categorized as non-functioning adenomas secrete gonadotropin
      and/or their subunits. In this paper, the clinicopathological characteristics of
      gonadotroph adenomas is reviewed.

PMID- 8254942
TI  - [Thyrotropin secreting adenoma].
AB  - Thyrotropin (TSH)-secreting pituitary tumor (TSHoma) is a very rare condition and
      is characterized by elevated serum thyroid hormone and unsuppressed TSH levels.
      Although in most patients, TSH and thyroid hormone levels are high, in several
      cases they are within normal range. There are several similar conditions such as,
      TSH secreting pituitary hyperplasia. Refetoff syndrome and so on. It is very
      difficult to differentiate these conditions. Hypersecretion of alpha subunit is a
      characteristic commonly seen only in TSHoma. Surgical excision is the first
      choice of treatment for this tumor but the prognosis is not good. Octreotide is a
      very useful drug that suppresses the TSH level.

PMID- 8254943
TI  - [Cushing's disease].
AB  - The following recent topics on the pathogenesis, unusual cases, treatment and the
      long-term prognosis of Cushing' Disease were presented and discussed. 1.
      hyperplasia of ACTH producing pituitary cell. 2. CRH producing tumor. 3. cyclic
      or periodic ACTH hormonogenesis. 4. pituitary cortisol resistance syndrome. 5.
      Carney complex and pituitary tumor. 6. GIP and PAH. 7. Superselective cavernous
      venous sampling. 8. Somatostatin analogue. 9. Results of Hardy' operation in
      Japan. 10. Long-term prognosis of 372 cases. 11. Opeprim treatment after Hardy's
      operation.

PMID- 8254944
TI  - [Pituitary non adenomatous tumor (Rathke's cleft cyst)].
AB  - Rathke's cleft cyst is one of many kinds of pituitary non-adenomatous tumors.
      Rathke's cleft cysts were evidenced by surgery in 7 cases from 7 to 87 years old.
      After the era of CT scan and MRI some cases were found incidentally after the
      head injury. Symptoms and signs of cases with Rathke's cleft cyst were headache,
      visual disturbances and/or diabetes insipidus. The lesion was high density on
      plain CT images and showed no-enhancement. The lesion on 2/3 cases showed high
      intensity on T1 weighted images and the others low. The lesion in half showed iso
      intensity on T2 weighted images and in other half high intensity. The stalk was
      deviated to lateral side in a case. Half lesion was in the sella and half was in
      supra-sellar region. The cyst was present in both intra-sellar and supra-sellar
      region in a case and showed a dumb-bell type. There are three approaches for
      removal of Rathke's cleft cyst. Hardy's transnasal approach was used on
      intrasellar type. The trans-Sylvian or anterior trans-interhemispheric approach
      was used on supra-sellar type. Content in the cyst was evacuated totally, and the
      cyst wall was removed as much as possible. However, the stalk should be protected
      from damage.

PMID- 8254945
TI  - [Recent progress in the diagnosis and treatment of hypopituitarism].
AB  - Measurement of basal pituitary hormone levels by IRMA made it possible to suspect
      even hypopituitarism because of the high sensitivity and specificity. Clinical
      application of TRH, LH-RH, CRF and GRF made it easier to diagnose pituitary
      reserves of individual pituitary hormones directly. Comparisons of GH or ACTH
      responses to ITT with those to CRF or GRF are especially useful for a
      differentiation of hypothalamic and pituitary lesions. A search for gene
      abnormality by various techniques may be necessary for a diagnosis of the nature
      of pituitary tumor as a cause of hypopituitarism. Replacement of growth hormone
      to adult GH deficiency is the greatest concern for future with a variety of
      dispute. Determination of plasma pituitary hormone levels is a good marker for a
      titration of a dosage of corticosteroid or thyroid hormone replacement.

PMID- 8254946
TI  - [Isolated ACTH deficiency associated with Hashimoto disease].
AB  - Isolated ACTH deficiency is a rare cause of secondary adrenocortical
      insufficiency. The diagnosis is made by the demonstration of low cortisol
      production with low plasma ACTH, absent adrenal responses to stimulation for
      pituitary or hypothalamus with intact adrenal response to exogenous ACTH, and
      normal secretory indices of other pituitary hormones. Although the pathogenesis
      of isolated ACTH deficiency is uncertain in most cases, autoimmune process is
      intimately involved as suggested by the histological evidence of lymphocytic
      hypophysitis and frequent observation of circulating antipituitary antibodies. In
      isolated ACTH deficiency, there have been occasional associations with Hashimoto
      disease which is characterized by the presence of a autoimmune mechanism. This
      suggests the possibility of common autoimmune process affecting both the
      pituitary and the thyroid gland.

PMID- 8254947
TI  - [Pituitary resistance to thyroid hormone].
AB  - Thyroid hormone resistance syndromes are characterized by unresponsiveness of
      target tissues to thyroid hormone and include a group of three disorders:
      generalized resistance, selective pituitary resistance and peripheral resistance.
      These patients are identified because they have persistently increased serum
      thyroxin (T4), triiodothyronine (T3) and normal or elevated thyrotropin levels.
      In case of selective pituitary resistance to thyroid hormone (PRTH), the
      peripheral tissues exhibit a normal response to T4 and T3 so that hyperthyroidism
      ensues. Recently cloning of T3 receptor has allowed detection of mutations in the
      T3 binding region of the T3 receptor gene, which provides strong evidence that
      P.R.T.H. represents part of the spectrum of generalized resistance to T3, rather
      than a separate entity.

PMID- 8254948
TI  - [Empty sella syndrome].
AB  - An empty sella is defined as a sella which, regardless of its size, is completely
      or partly filled with cerebrospinal fluid (CSF). Empty sella is occasionally
      found as a normal anatomical variation, which is referred to as primary empty
      sella. On the other hand, empty sella is also seen after surgery, irradiation or
      medical treatment of pituitary adenoma, which is called secondary empty sella.
      Magnetic resonance imaging (MRI) is useful in diagnosing empty sella. Primary
      empty sella is usually free from clinical symptoms but sometimes associated with
      headache, obesity, visual disturbance, non-traumatic CSF rhinorrhea and pituitary
      insufficiency. These associated findings constitute the empty sella syndrome. CSF
      rhinorrhea, visual disturbance and severe increased intracranial pressure are the
      indications for surgical treatment. Non-symptomatic cases require no treatment
      but periodical follow up is necessary.

PMID- 8254949
TI  - [Recent progress in the diagnosis and treatment of diabetes insipidus].
AB  - Recent progress in the diagnosis and treatment of diabetes insipidus (DI) is
      reviewed. Response of plasma vasopressin (AVP) to 5% hypertonic saline can be a
      new indicator of the capacity of AVP response to osmotic stimuli. Marked progress
      in the imaging analysis by computed tomography and magnetic resonance imaging
      (MRI) has made it possible to evaluate hypothalamic-pituitary lesions in detail.
      Especially, signal intensity on T1-weighted MR image of neurohypophysis is
      suggested to reflect its function. Sequencing analysis of genes encoding AVP
      neurophysin precursor or AVP receptor is expected to be a most useful method for
      the diagnosis of inherited DI. Intranasal administration of DDAVP (1-deamino-8-D
      AVP) is recommended as a standard therapy for DI.

PMID- 8254950
TI  - [Current technical aspect in transsphenoidal pituitary adenomectomy].
AB  - The authors describe several useful surgical techniques from our experiences in
      transsphenoidal microsurgery for pituitary adenomas. Intentional two-staged
      transsphenoidal removal with open sella floor and intrasellar drainage is
      available for most of giant adenomas with suprasellar extension. The open sella
      floor method and intrasellar drainage after first transsphenoidal adenomectomy
      accelerate to decrease the suprasellar tumor extension. In four of six patients
      in our series, macroscopically total selective adenomectomy was achieved by a
      second transsphenoidal operation without complications. As for extremely small
      microadenomas, represented in patients with Cushing's disease, stepwise systemic
      search is required to identify a subcortical microadenoma, preserving
      postoperative pituitary function. Edge resection around the microadenoma is also
      necessary for normalization of hormonal hypersecretion and permanent cure.

PMID- 8254951
TI  - [Medical management after pituitary surgery].
AB  - Although the majority of patients with pituitary tumor, undergoing
      transsphenoidal microsurgery, have a low incidence of hormonal deficiency after
      surgery, the endocrinological evaluations should be carefully done before and
      after surgery. Glucocorticoid replacement is necessary in patients with Cushing's
      disease during and after surgery as well as those with adrenal insufficiency.
      Repeated CRF test is useful to assess the secondary adrenal insufficiency of
      Cushing's disease after surgery. Patients with impaired secretion of both ACTH
      and TSH should receive glucocorticoid replacement before thyroid hormone
      replacement in order to avoid adrenal crisis. A combination of CRF, GRF, TRH and
      GnRH is a safer and more reliable test to evaluate pituitary function than the
      conventional triple test consisting of insulin, TRH and GnRH, especially in
      patients predicted to have pituitary-adrenal insufficiency. Diabetes
      insipidus(DI), immediately after pituitary surgery, should be treated with
      subcutaneous injection of Pitressin. Even if patients seem to have recovered from
      DI several days after surgery, they must be monitored closely because of the
      incidence of triphasic DI. Less attention has been given to replacement for GH
      deficiency in adults. Recent reports revealed that GH replacement in adults with
      GH deficiency decreases visceral fat tissue and increases plasma calcium,
      phosphorus, osteocalcin and procollagen III levels. GH replacement will become
      more popular even in adults. Many options and technological advantages in the
      diagnosis and treatment of pituitary tumors have developed in a decade. In the
      near future, post-operative patients with pituitary tumors must be cared for in
      view of the "quality of life".

PMID- 8254952
TI  - [Biomacromolecules studied by atomic force microscopy].
AB  - Recent studies of biomacromolecules by atomic force microscopy are summarized.
      The resolution and reproducibility of AFM when applied to soft biosamples has
      been gradually improved and AFM is now recognized as a most promising technology
      in nanometer scale observation and manipulation of biological structures.

PMID- 8254953
TI  - [Biosensors comprising DNA as receptive component].
AB  - Most of biosensors rely on proteins, including enzymes and antibodies. In
      addition to such proteins, DNA is also an important host molecule in biological
      recognition. Sensors comprising DNA, single and/or double strands, as a receptive
      component would be useful in detecting complimentary DNA as well as DNA-binding
      molecules and ions. In this article, coupling methods for DNA with solid
      substrates are discussed. New strategies for detecting the interaction of
      analytes with the immobilized DNA are reviewed. The DNA duplex modified electrode
      is proposed to have a potential for determining binding constants of a series of
      DNA-binding drugs.

PMID- 8254954
TI  - [Chronopharmacology and DDS (drug delivery system)].
AB  - Rhythmic variations, including circadian and circannual ones, have been
      demonstrated in the pharmacokinetics and pharmacodynamics of many drugs. These
      suggest that the consideration of the timing of drug administration will improve
      rational drug therapy, increasing drug efficacy and safety. A drug delivery
      system (DDS) enabling a constant-rate administration is attractive from the
      clinical point of view, namely, such a system could minimize the peak and trough
      variation in plasma drug concentration after dosing so as to avoid toxicity
      associated with drug levels exceeding the upper limit of therapeutic range and
      lack of effect with drug levels dropping below the lower limit of the range.
      However, pulsatile administration is preferred for peptide and hormone
      pharmacotherapy. For chronopharmacotherapy, a pattern of input at different
      release rates is also preferred to that at a constant rate. These findings
      emphasize the need to consider chronopharmacology in DDS design.

PMID- 8254955
TI  - [The current state of surgical pathology of the breast--the practice in our
      department].
AB  - The following developments have considerably influenced the pathological
      management of breast materials: The wide use of aspiration cytology, increase of
      specimens from small non palpable lesions detected by mammography, an increase of
      cases difficult to diagnose histologically, increase in the number of
      conservative surgery cases which require examination of semi-serial sections, and
      the development of immunohistochemical procedures using breast cancer tissues.
      Under these changing circumstances in the department of pathology, we report our
      current practices and some of the results; About 75% of breast cancer cases
      initially treated in our hospital were diagnosed by aspiration cytology only. A
      retrospective, simulation study on quadrantectomy of breast cancers for selected
      T1N0N1a examined by semi-serial sections in non-conservative mastectomy cases
      revealed residual carcinoma foci located in a region outside the primary quadrant
      in about 25% cases. GCDFP-15 (Gross cystic disease fluid protein-15) is a fairly
      specific marker for breast cancer. Good correlation was obtained using estrogen
      and progesterone receptors routinely measured by ICA (Immunocytochemical assay),
      instead of the biochemical method using DCC (Dextran-coated charcoal). c-erbB-2
      and p53 which were positive in 45.8%, and 28.6%, respectively, in our breast
      cancer cases, seemed to be good markers of biological malignancy in the breast
      cancer.

PMID- 8254956
TI  - [Clinical usefulness of tumor markers in breast cancer].
AB  - Currently, many tumor markers are routinely measured in patient serum, but none
      appears to adequately detect cancer-specific substances for breast cancer. Four
      tumor markers (CEA, CA15-3, BCA225, c-erbB-2) were compared for sensitivity and
      specificity to breast cancer in 393 patients with breast disease (fibrocystic
      disease; 40, benign tumor; 21, primary cancer; 22, recurrent or advanced cancer;
      22, non-recurrent; 288), and the following results were obtained: In cases of
      primary breast cancer excluding stage IV cases, the positive rates of CEA, CA15-3
      and BCA225 were 4.5%, 13.6% and 13.6%, respectively. These rates were not higher
      than the positive rates found in fibrocystic disease or benign tumor. In cases of
      recurrent or advanced breast cancer, the positive rates of CEA, CA15-3, BCA225
      and c-erbB-2 were 31.8%, 50.0%, 40.9% and 27.3%, respectively. In the recurrent
      cases, the combination assay using CA15-3, BCA225 and c-erbB-2, showed more
      useful diagnostic value (72.7%) than other combination assays with three tumor
      markers. High levels of CA15-3 in eight cases, BCA225 in five and CEA in one were
      found during the follow up of 15 patients with initial recurrence. Serum c-erbB-2
      exceeded the normal range in 6 of 7 cases with advanced breast cancer. Serum c
      erbB-2 should be considered a marker of progressive breast cancer. These results
      suggested that CA15-3, BCA225, c-erbB-2 and combination assays are useful tumor
      markers for not only detecting the recurrence of breast cancer, but also
      diagnosing the progression of primary breast cancer.

PMID- 8254957
TI  - [The surgical management of breast cancer, especially breast conserving
      treatment].
AB  - The management of breast cancer is highly controversial. Various operations have
      been performed at different hospitals. Herein, we reviewed the results of
      randomized clinical trials regarding breast conserving treatment, and axillary
      and internal mammary lymph node dissections. Variations in local-regional therapy
      may not substantially affect survival, but the incidence of local-regional
      failure is inversely related to the extent of operation and/or radiotherapy. At
      present, surgeons are highly recommended to perform adequate surgery which
      provides the ultimate local control, does not compromise the chance for cure and
      gives the best cosmetic and aesthetic results. Therefore, quadrantectomy with or
      without immediate reconstruction, axillary dissection and internal mammary biopsy
      and breast irradiation are more preferably recommended for ensuring local control
      and for providing a better cosmetic and psychological impact.

PMID- 8254958
TI  - [Systemic adjuvant chemo-endocrine therapy after breast conservation treatment
      for breast cancer].
AB  - The majority of patients who have undergone breast conserving surgery proved to
      be node-negative. Node-negative breast cancer has a fairly good prognosis,
      achieving a 10 year disease-free survival rate of 88%. Patterns of recurrence and
      relapse in node-negative cases are characterized by a higher ratio of
      hematogenous metastases after relatively longer disease-free intervals. Such
      cases have been considered the best indications of systemic adjuvant therapy.
      Postoperative adjuvant trials using cyclophosphamide (CPA) and/or tamoxifen (TAM)
      were conducted at the Aichi Cancer Center Hospital, and the following results
      were obtained concerning adjuvant treatment for early-stage (node-negative or
      stage I) breast cancer; (1) In the post-menopausal group, CPA and/or TAM
      administration was recommended as the treatment of choice. (2) In the
      postmenopausal group, TAM was evaluated as the key drug. After TAM alone or TAM
      plus CPA administration, an improvement in the disease-free survival rate was
      expected. (3) After administration of CPA alone in the postmenopausal group,
      there were no demonstrable benefits. On the contrary, adverse effects were
      suspected. (4) The risk of contralateral breast cancer was reduced to two-thirds
      when TAM was administered as an adjuvant therapy.

PMID- 8254959
TI  - [Study on platelet satellitism].
AB  - The platelet leukocyte adherence phenomenon, so-called 'Platelet Satellitism
      (PS)', was recognized on peripheral blood smear from ethylenediaminetetraacetic
      acid (EDTA)-anticoagulated blood in two patients. The present study was
      undertaken to elucidate both inducing and inhibitory factors for PS by utilizing
      two patients' blood. Both heparin and sodium citrate could not induce PS in these
      patients. This phenomenon was inhibited by anti-platelet membrane glycoprotein
      (GP) IIb/IIIa complex antibody (AP-2), but not by antibodies against platelet
      membrane glycoprotein (GP) Ib/IX complex, fibrinogen and von Willeb and factor.
      Patients' sera were subjected to column chromatography of Sephacryl S-300 to
      obtain immunoglobulin (Ig) G, IgA and IgM fractions. In one patient, IgG
      fraction, but neither IgA nor IgM fractions could induce PS phenomenon in normal
      whole blood, while IgA but neither IgG nor IgM could induce PS in another
      patient. Furthermore, when purified IgG from the first patient was treated with
      2U/ml of plasmin to digest Fc portion, PS phenomenon disappeared. The F(ab')2
      portion was prepared from whole IgG treated with pepsin, then added to normal
      whole blood. Purified F(ab')2 fragment by itself could not induce PS phenomenon,
      whereas the preincubation of F(ab')2 in normal whole blood could inhibit the PS
      caused by the patient's whole IgG. These results indicate that platelet membrane
      glycoprotein (GP) IIb/IIIa complex and both Fab and Fc portions of immunoglobulin
      might be necessary to induce PS phenomenon in EDTA-anticoagulated whole blood.

PMID- 8254960
TI  - [Age and sex dependent distribution pattern and normal range of blood cell
      parameters obtained by automated blood cell analyzer].
AB  - Distribution and normal value of 23 blood cell parameters in healthy 2509 males
      and 1658 females (20-69 year of age) who are the visitors of our health
      examination clinic or workers of the hospital were studied. These parameters were
      obtained by automated cell analyzer (Sysmex NE-8000, Toa Med. Electronics).
      Distribution pattern and normal range of 23 parameters were studied in different
      groups of the sex and the age (decade). Distribution of the parameters in each
      groups was classified into 5 patterns such as Gaussian (G), log-Gaussian (L),
      skewed toward lower values (P1), skewed toward higher values with shorter tail
      than of log-Gaussian (P2), skewed toward higher values with longer tail than of
      log-Gaussian (P3). Normal range of parameters in each groups was calculated by
      mean +/- 1.96SD of normal distribution curve obtained by power transformation
      procedure in L, P1, P2 and P3 distribution. Parameters concerning leukocytes and
      platelets showed rarely G distribution in each groups. Significant sex difference
      was observed in leukocyte count (male > female, p < 0.001) and platelet count
      (female > male, p < 0.01) in each age group. Normal values of newly analysed
      parameters as volume distribution curve of erythrocytes and platelets, mean
      platelet volume and large platelet ratio were established.

PMID- 8254961
TI  - [A basic study on a highly sensitive automated method for hypercoagulable state
      in plasma, fluorogenic prothrombin time (FPT) method].
AB  - A highly sensitive automated method, fluorogenic prothrombin time (FPT) method,
      was developed by a combination of a fluorogenic peptide substrate for thrombin
      and a centrifugal autoanalyzer (Cobas Bio). Using plasmas from stroke patients,
      we showed that the second reagent containing fluorogenic peptide substrate should
      be mixed after the first reagent containing tissue factor and plasma were mixed,
      that is, two steps method, in order to detect hypercoagulable state. When the
      first and the second reagent were mixed with plasma at the same time, that is,
      one step method, FPT was not sensitive to hypercoagulable state. We also showed
      that patient plasmas should be stored at -80 degrees C and subjected to FPT
      analysis immediately after thawing, not leaving at 4 degrees C or room
      temperature. Good correlation was observed on FPT of stroke patients using human
      tissue factor and bovine tissue factor. Another fluorogenic method was developed
      by the same principle for the evaluation of factors X and VII concentrations in
      plasma using deficient plasma of factor X or factor VII. Good correlation was
      observed on factors X and VII concentrations of stroke patients using human
      tissue factor and bovine tissue factor.

PMID- 8254962
TI  - [Detection of methicillin-resistant Staphylococcus aureus using PCR and non
      radioactive DNA probes (II)].
AB  - Methicillin resistance in staphylococci is primarily due to the presence of a mec
      A gene which encodes the novel penicillin-binding protein 2'. Some chromosomal
      factors, fem A and fem B, also participate in the expression of methicillin
      resistance in S. aureus. This study was designed to detect mec A, fem A and fem B
      genes for identification of staphylococcal species and for discrimination of
      methicillin-resistant cells. Three different pairs of DNA primers (PBP2'AF
      PBP2'AR, fem AF-fem AR and fem BF-fem BR) complementary to unique regions of mec
      A, fem A and fem B genes were synthesized for use in polymerase chain reaction
      with DNAs of methicillin-sensitive S. aureus (MSSA), S. epidermidis, methicillin
      resistant S. aureus (MRSA) and S. epidermidis. Amplified target DNAs of 630, 509,
      and 651 bp were resolved on ethidium bromide-stained gel, and hybridized to DNA
      probes conjugated to alkaline phosphatase. When applied to pure cultures on the
      MRSA screen agar, all three DNA probes tested detected MRSA in 47 of 61 culture
      positive specimens (77.1%); the detection ratio of MRSA with mec A and either fem
      A or fem B probes was increased to 95.9%. By contrast, the fem A and fem B probes
      did not detect S. epidermidis. The result of detecting these species streaked on
      mannitol-salt agar were similar, while the detection of MSSA with the fem A and
      fem B probes was incomplete irrespective of the presence or absence of mec A.
      These findings suggest a good correlation between cultivation and DNA probe assay
      with respect to MRSA detection.

PMID- 8254964
TI  - [Sensitive detection of K-ras oncogene codon 12 mutations by nested PCR using
      mismatched primers and selective digestion of non-mutated PCR fragments with
      restriction enzyme].
AB  - Sensitive detection of K-ras oncogene mutation at codon 12 using nested
      polymerase chain reactions (PCR) with mismatched primers combined with selective
      digestion of nonmutated DNA fragments after the first PCR amplification was
      reported by Levi S, et al. (Cancer Res 51:3497-3502, 1991). We examined the
      usefulness of this novel technique in cell lines carrying various K-ras codon 12
      mutations and clinical samples such as colon carcinoma tissue, corresponding
      normal colonic mucosa and pancreatic juice obtained from the patients with
      pancreatic carcinoma undergoing endoscopic retrograde pancreatography (ERP). In
      analysis of tumor cell lines carrying mutated K-ras at codon 12, the fragment
      length of the amplified DNA was 135 bp after digestion using restriction enzyme
      BstN1, whereas those of nonmutated cell lines were 106 bp. This method was highly
      sensitive to detect mutant DNA diluted at a ratio of 2048 fold with normal DNA
      samples obtained from peripheral blood lymphocytes. In analysis of clinical
      samples, 4 out of 10 colorectal carcinoma tissues were positive for K-ras gene
      mutation at codon 12, however, no mutations were detected in corresponding normal
      colonic mucosa. In analysis of pancreatic juice taken from the patients with
      pancreatic carcinoma, 1 out of 3 samples were positive for K-ras mutation at
      codon 12. Thus, this novel approach was thought to be useful for detection of
      minimum number of cancer cells from compound samples containing larger amounts of
      normal cells.

PMID- 8254963
TI  - [Detection of HPV infection in CIN and invasive cancers by in situ hybridization
      method--comparison with histopathology].
AB  - The causal association of human papilloma virus (HPV) with cervical cancer has
      been supported by multiple lines of evidence. Therefore, in the case of
      dysplasia, the presence of HPV-DNA should be detected and its subtypes
      identified. This is important in the determination of the prognosis for cervical
      disease. We reported a study in which the localization and types of HPV in
      cervical diseases was identified by in situ hybridization using biotin-labelled
      DNA probes. Seven types (3 basic forms) of HPV were used as DNA probes. HPV types
      used were following: 6/11, 16/18, 31/33/35. In this study, we introduced 7 new
      types (3 forms) of probes for a total of 14 types (6 forms). The new probes
      introduced were 42/43/45, 45/56, 51/52. Using these probes, the rate of detection
      HPV according to types was examined. In addition, localization of HPV infection
      and its relationship with histopathological findings of cervical disease were
      evaluated. 1) Types 6/11 and 45/56 were found in the lesions with less important
      histological findings (CIN I). Types 16/18, 31/33/35, 51/52 were found in the all
      lesions. Type 42/43/44 were not detected in this study. 2) The addition of 7 new
      types (3 new forms) of probes resulted in a 17% increase (16 cases) in the rate
      of detection of HPV compared to our previous study. 3) Localization and
      distribution pattern of the HPV is not, as has been reported so far, dependent on
      HPV type but rather on the histological characteristics, such as the degree of
      dysplasia.

PMID- 8254965
TI  - [Basic and clinical evaluation of EIA (pin immuno assay, PIA) kit for
      antithyroglobulin antibody (TGAb) and antimicrosomal (antiperoxidase) antibody
      (TMAb)].
AB  - Newly developed enzyme immunoassay kit (Pin Immuno Assay, PIA) for quantitative
      determination of serum antithyroglobulin antibody (TGAb) and antimicrosomal (
      peroxidase) antibody (TMAb) was evaluated. The method utilizes the Sandwich ELISA
      principle with a unique micropin as solid phase coated with antigen.
      Reproducibilities assessed by intra- and interassay variation were less than 6.9%
      (CV) and 7.2% for TGAb or 4.2% and 6.0% for TMAb respectively. Changes in the
      first or second incubation time did not affect both TGAb and TMAb values. Upper
      normal limits obtained from 47 healthy subjects were 150 IU/ml for TGAb and 25
      IU/ml for TMAb. Positive results in TGAb were obtained 60.0% in patients with
      Graves' disease and 80.0% in chronic thyroiditis and in TMAb 77.8% in Graves'
      disease and 66.7% in chronic thyroiditis. Patients with other autoimmune diseases
      such as SLE, RA were also found high incidence of positive results, 48.3% for
      TGAb and 65.0% for TMAb respectively. These results indicate that the
      nonradioisotopic assay technique for thyroid autoantibodies are useful in
      diagnosis of autoimmune diseases especially thyroid diseases.

PMID- 8254966
TI  - [A simple and rapid method capable of detecting methicillin-resistant
      Staphylococcus aureus (MRSA) by single culture on an agar plate].
AB  - A novel simple agar plate capable of detecting methicillin-resistant
      Staphylococcus aureus (MRSA) by single culture was developed. The agar plate
      included 1) mannitol and a pH indicator, and 4-methylumbelliferyl phosphoric
      acid, both for identification of Staphylococcus aureus by its ability to digest
      mannitol and produce phosphatase; detection of the former by change in color of
      pH indicator and the latter by fluorescence of 4-methylumbelliferone, 2)
      oxacillin at a minimum concentration just to eliminate methicillin-sensitive
      Staphylococcus aureus (MSSA), and 3) phenylethyl alcohol to inhibit growth of
      most gram negative rods. The method was simple, sensitive, time-saving, and quite
      effective in the identification of MRSA directly from clinical specimens. Neither
      false positive nor false negative results were observed by the present method.

PMID- 8254967
TI  - [Myocardial metabolism during dynamic exercise].
AB  - The development of Webster catheterization has enabled us to make clinical
      measurement of coronary sinus blood flow and to estimate the kinetics in
      myocardial substrate uptake. In this study, exercise tolerance test using supine
      multistage bicycle ergometer test was performed and exercise-induced hemodynamic
      alteration was evaluated in 18 patients with ischemic heart disease (16 males and
      2 females, average age 56.3 years). The change in substrate kinetics in
      myocardial metabolism was also examined in terms of two indexes; myocardial
      uptake rate and myocardial uptake. The following results were obtained. 1) The
      myocardial uptake rates of glutamate and free fatty acid were significantly
      decreased by exercise, while those of glucose and lactate showed no significant
      change. 2) The myocardial uptakes of glutamate, glucose and lactate were
      significantly increased by exercise, but that of free fatty acid did not change
      significantly. 3) A significant negative correlation (r = -0.52, p < 0.05) was
      observed between the change in myocardial glutamate uptake and the change in
      pulmonary artery wedge pressure induced by exercise, suggesting that patients
      with ischemic heart disease might fail in glutamate uptake induced by exercise.
      The difference in the kinetics of myocardial uptake rate and myocardial uptake
      for glutamate, alanine, glucose, free fatty acid and lactate is observed. This
      difference occurs from the decrease in uptake rate due to the increase in
      coronary sinus blood flow. Myocardial uptake, which directly reflects myocardial
      energy metabolism is regarded as a more useful index of myocardial metabolism
      than myocardial uptake rate.

PMID- 8254968
TI  - [Evaluation of hyperlipidemia in high school student--Part 1].
AB  - Recently the risk of ischemic heart disease (IHD) is increasing in young
      generations. Thus, we evaluated the degree of hyperlipidemia in the students of
      high school in Miyagi prefecture. At first, we examined the plasma level of total
      cholesterol in all students as screening. About 10% of all the students showed
      high level of total cholesterol over 200mg/dl. For second screening, we examined
      further indexes for hyperlipidemia including lipids, glucose and blood pressure
      at fasting state and got information about family history, diet and exercise.
      There was positive correlation between total cholesterol and LDL-cholesterol (LDL
      C), but no relation was found among others. Lipoprotein (a) which was an
      independent factor of IHD showed a broad distribution as described before, and
      had no relation with other lipid levels. Early education and a familial
      consultation for protecting from IHD should be followed after the screening of
      lipids levels.

PMID- 8254969
TI  - [Myelodysplastic syndrome developing acute myelocytic leukemia with gastric
      mucormycosis].
AB  - 80-year-old female was admitted to our hospital because of pancytopenia. Her
      peripheral and bone marrow examinations were performed. According to the criteria
      of FAB classification, the diagnosis was myelodysplastic syndrome (refractory
      anemia with excess of blasts in transformation). Etoposide was administered to
      decrease leukemic blasts. However, she still had high fever and increasing of
      CRP. Hematological data also showed the increasing of WBC count, blast cells, and
      LDH enzyme. Antibiotics and anti fungal drugs were also not effective. She died
      of respiratory failure, although the cautions and extensive treatment was tried.
      Autopsy findings revealed proliferation of mucor in the mucosa of stomach. So, we
      reported here a very rare case of gastric mucormycosis, localizing exclusively in
      the stomach which was difficult to diagnose while she was alive.

PMID- 8254970
TI  - [Cytomegaloviral inclusions detected in the seminal vesicle, ductus deferens and
      lungs in an autopsy case of lung cancer].
AB  - We report a case of cytomegalovirus infection of the seminal vesicle and ductus
      deferens in a 32-year-old Japanese man with papillary adenocarcinoma of the lung.
      Although the lungs are usually a target organ of cytomegalovirus infection, most
      organs can be involved. However, the male reproductive system has rarely been
      reported infected with the virus. H.E. sections of our case showed
      cytomegaloviral inclusions in many ductal epithelia of the seminal vesicle and
      ductus deferens as well as macrophages of the lungs. Immunohistochemistry using
      monoclonal antibody to cytomegalovirus disclosed viral antigenicity in these
      infected cells. Electron microscopy recovered enlarged infected cells packed with
      viral nucleocapsids approximately 100 nm in size. These nucleocapsids were
      enveloped in the cytoplasm and consistent with the Herpesviridae family. To our
      knowledge, our case is the first report of cytomegalovirus infection of the
      seminal vesicle and ductus deferens in the English and Japanese literature.

PMID- 8254971
TI  - [Analysis of abnormal alkaline phosphatase in patient with high alkaline
      phosphatasemia].
AB  - We describe here a 69-year-old male with high serum alkaline phosphatase (ALP)
      activity who was showed high alkaline phosphatasemia. High ALP level, 112.4 K.A.
      was found in his serum. But, except for ALP, all other laboratory data including
      cancer markers were within normal range in this case. An electrophoretic pattern
      of patient ALP isozyme without neuroaminidase digestion showed liver-type ALP,
      but the ALP isozyme pattern with neuraminidase digestion from Vibrio Cholerae was
      identified as bone-type ALP. Moreover, the patient ALP reacted with anti-bone ALP
      MoAb. The apparent molecular size of patient ALP was 160kDa similar to bone ALP.
      Furthermore, we investigated the multiformity of the sugar chain(s) of patient
      ALP by serious lectin affinity chromatographies. From these results, the increase
      of multiantennary complex type and/or bisecting GlcNAc type sugar chain(s) of ALP
      was shown in patient serum. These results suggested that the patient might have a
      distant metastasis as in a case of carcinoembryonic antigen described previously.
      Besides, patient urinary pyridinoline and deoxypyridinoline was high level
      comparing normal adult urine. From detailed bone survey, the patient was observed
      the bone metastasis of cancer. Thus, the measurement of ALP sugar chain
      subfractions may be useful for diagnosis of patient with bone metastasis of
      cancer.

PMID- 8254973
TI  - [Characterization of human immature T cell precursors in fetal liver and
      postnatal thymus].
AB  - The sequence of events that accompany development of immature T cell precursors
      in man is not precisely known. Recently, we identified subpopulations of
      thymocytes that may represent intermediate stages between CD3-CD4-CD8- (TN) and
      CD3+CD4+CD8+ (DP) thymocytes. Multicolor analysis provided evidence for the
      existence of CD3-CD4+CD8- and CD3-CD4+CD8 alpha+beta- populations. In vitro
      culture of TN thymocytes with IL-7 gave rise to cells of these phenotypes,
      suggesting that the novel subpopulations we found are the progeny of TN
      thymocytes. Expression of CD34 was detected on most of TN thymocytes and
      progressively reduced as cells differentiate. The novel subpopulations were shown
      to express CD34. 6-22-week-old human fetal liver cells were also analyzed in
      search for the possible prethymic T cell precursors. It was revealed that most of
      CD3-CD7+ cells which had been considered as T cell precursors were CD34-CD56+ and
      exhibited non-MHC-restricted cytotoxicity. Thus, although they expressed
      cytoplasmic CD3 antigens, these cells seemed to represent NK cells rather than T
      cell precursors. Existence of the latter is still to be demonstrated.

PMID- 8254972
TI  - [Histidine-rich glycoprotein in diabetics].
AB  - Histidine-rich glycoprotein (HRGP) has been believed to have anti-fibrinolytic
      activity through its binding to plasminogen. Diabetic complications such as
      retinopathy or nephropathy are considered to be related to impaired coagulation
      fibrinolysis system. Therefore, we studied the serum levels of HRGP in diabetics.
      There were no significant alterations of serum HRGP levels in comparison with
      normal controls, nor was there a mutual relation between HRGP levels and HbA1
      values. Moreover, the molecular weight of HRGP was not deviated from control.
      These results suggest that HRGP might not have critical role on fibrinolytic
      system in diabetics.

PMID- 8254974
TI  - [Phenotypic analysis of immature T-lineage cells].
AB  - The characteristics of very immature T-lineage blasts including co-expression of
      myeloid properties and the distinctions between the phenotypes of pro-thymic
      (CD7+ CD5+ CD2+ CD3- CD4- CD8- or more immature) and thymic (CD3- CD4+ CD8+ or
      more mature) blasts are shown. The lineage-derivation of CD7+ CD5- CD2- and CD7+
      CD5+ CD2- lymphoid blasts was investigated based on the gene expression of CD3
      epsilon, CD3 delta and myeloperoxidase (MPO). The former group included 4
      categories; undifferentiated blasts without commitment to myeloid or T-lineage, T
      lineage blasts with mRNA of CD3 epsilon, T/myeloid blasts with mRNA of CD3
      epsilon and MPO and blasts with mRNA of MPO. The latter included 2 categories; T
      lineage blasts with CD3 epsilon and CD3 delta mRNA and T/myeloid blasts with CD3
      epsilon, CD3 delta and MPO mRNA. Thus, CD3 epsilon was expressed at a more
      immature stage than CD3 delta. The blasts at the pro-thymic stage were different
      from those at the thymic stage in several respects. The T-cell receptor (TCR)
      beta-chain gene showed a germ-line configuration in most pro-thymic blasts. The
      CD13/CD33, CD11b and class II MHC antigens were expressed very frequently in the
      pro-thymic stage. The CD21 antigen was most selectively expressed at the thymic
      stage. Pro-thymic blasts were of RA type of CD45 antigen, while thymic blasts
      were of RO type. Recombination activation gene-1 (RAG-1) was only limitedly
      expressed at the pro-thymic stage, but was highly expressed at the thymic stage.
      These findings indicate that there are distinctive differences before and after
      the initiation of clonal selection which is unique and thymus-specific, and that
      the neoplastic cells represent each stage of T-lineage differentiation involving
      the unique thymic function.

PMID- 8254975
TI  - [Present and future of flow cytometry].
AB  - Flow cytometry is used for lymphocyte subset identification and leukemia typing.
      In routine laboratories, leukocyte differentiation and reticulocyte counting are
      also common uses for flow cytometry. Flow cytometers provide accurate and precise
      data with simple manipulation. The disadvantage of flow cytometry is the low cost
      efficiency as a clinical test. Dual color analysis is a recent trend and more
      information on cells can be obtained, though the selection of antibody subclass
      sometimes leads to incorrect results. As technology develops, however, flow
      cytometry becomes more feasible in routine clinical laboratories, and the number
      of clinical uses will increase.

PMID- 8254976
TI  - [Standardization in flow cytometry].
AB  - Analysis of lymphocyte subsets and determination of leukemic cells by flow
      cytometry has now become an important clinical test. With recent technological
      developments, reliability was improved and the procedure became easier. To
      establish quality assurance procedures for flow cytometry, standardization is
      necessary. In the United States, the National Committee for Clinical Laboratory
      Standards (NCCLS) has been working actively and has published several tentative
      guidelines. However, in Japan, such work lags behind that in western countries.
      The results of quality control surveys show that differences in data exist among
      instruments and laboratories. To minimize such differences, nation-wide
      surveillance must be established. Also, efforts should be made to establish
      reference methods and reference materials that will lead to standardized results.
      We hope standardization will ensure precision and accuracy in flow cytometric
      results in clinical laboratories.

PMID- 8254978
TI  - [Analysis of anti-platelet antibodies using flow cytometry].
AB  - We analyzed the production of anti-platelet antibodies by alloimmunization in
      patients with hematological disorders who receive blood transfusions frequently.
      HLA antibodies were detected by anti-human globulin lymphocyte cytotoxicity test
      (AHG-LCT), and anti-platelet antibodies by flow cytometry (FCM). Results from FCM
      correlated well with those of AHG-LCT. The rate of coincidence was 92.1%.
      Production of alloantibodies in patients was detected in 32.7% in the without
      filter group, but decreased to 17.1% (p < 0.05) in the filter group. The avidin
      biotin assay and concentration of globulin fraction in patient's serum by affi
      gel blue column were useful for increasing sensitivity in detecting anti-platelet
      antibodies. Anti-platelet specific antibodies were detected in 5 patients (5/226;
      2.2%) and these antibodies coexisted with HLA antibodies in all patients. The
      antibody in 3 of these patients were identified as HPA-2b (Siba), and those in
      the other 2 patients were combined antibodies on platelet identification panel
      and immunoblotting. It may be possible that high titer serum of anti-platelet
      specific antibodies could be identified by its fluorescent intensity. Measures
      against HPA-2b are considered necessary because platelet specific antibodies were
      produced in 2.2% of patients who received blood transfusions frequently.

PMID- 8254977
TI  - [Flow cytometry in clinical laboratory medicine].
AB  - Flow cytometric analysis of blood cells is an important technique for the
      evaluation of the immunological functions of patients with various disorders, and
      also for the differential diagnosis of leukemias. In the lymphocyte subset
      analysis, special attention should be paid to the optimal gating of lymphocytes.
      We recommend the use of CD13 and CD33 to ascertain more accurate gating of
      lymphocytes and more efficient monitoring of the contamination of non-lymphoid
      cells, especially in patients with PNH, in addition to CD45 and CD14, which are
      already utilized routinely. We also feel that 2-color and 3-color analyses should
      be applied more frequently for the routine laboratory tests for lymphocyte
      subsets. With regard to the analysis of leukemia cells, the combined use of
      nuclear DNA content or TdT (terminal deoxynucleotidyl transferase) with other
      routine cellular markers is quite useful for the analysis of a small number of
      leukemia cells, and enables the differentiation of leukemia cells from the
      contaminating non-malignant cells, particularly in the analysis of the minimal
      residual diseases. Among the cellular markers defined by specific monoclonal
      antibodies, we stress the physiological significance of recently developed cell
      adhesion molecules, such as selectins and their carbohydrate ligands, which are
      closely involved in the recruitment of leukocytes in inflammatory responses, as
      well as in the infiltration processes of leukemia cells.

PMID- 8254979
TI  - [Education in medical ethics].

PMID- 8254981
TI  - [Current ethical problems in Japan].

PMID- 8254980
TI  - [Ethics in the aging population: a gastroenterologist's perspectives].

PMID- 8254982
TI  - [Liver transplantation: the Danish experience].

PMID- 8254983
TI  - [Liver transplantation: the Australian experience].

PMID- 8254984
TI  - [Current status of liver transplantation (LT)in France and specificities of
      French ethical attitudes concerning LT].

PMID- 8254985
TI  - [Liver transplantation in Italy and the scarcity of donors: causative factors and
      ethical considerations].

PMID- 8254986
TI  - [Promotion of ethics in gastroenterology: joint meeting of the members of JSGE
      and OMGE].

PMID- 8254987
TI  - EEG power spectrum changes due to listening to pleasant music and their relation
      to relaxation effects.
AB  - Electroencephalogram (EEG) power spectrum changes induced by pleasant music (2
      min. fractions of 6 samples of music [famous classical and commercially available
      "alpha music" at 10-sec. intervals]) were investigated in relation to changes in
      16 kinds of psychosomatic feelings. Subjects were 42 healthy young people aged 18
      25 yrs. Two major components, "pleasant & relaxed" and "calm", were extracted
      through principal component analysis of the feeling changes, both of which were
      related to the "relaxation effects" of the music. These component scores were not
      related to the changes of EEG powers in the delta, theta, alpha and beta
      frequency components in 6 regions (frontal, parietal and occipital regions of the
      left and right hemispheres), when examined separately. However, the change of the
      total delta power for all the regions was significantly associated with both the
      "pleasant & relaxed" and "calm" component scores. The association between the
      total theta power change and "calm" score was found to be insignificant if the
      type-A personality variable was added to their regression model. On the other
      hand, the alpha-peak frequency was inversely related to the decrease of the
      "calm" score in the left occipital region (LO). The reduction of the alpha-peak
      power in the LO was also significant, and was associated not with the alpha-peak
      frequency changes but inversely with the "calm" score, although these alpha
      component changes were not shown to be modified by the personality. Thus, the
      present study suggests, as a preliminary finding, that the "relaxation effects"
      of pleasant music can be associated with the EEG power spectrum component
      changes, especially with the change in the total theta power and possibly with
      that in the alpha power in the occipital, and the frequency shift of the peak in
      the alpha-range. Some of the associations were also shown to vary for the type-A
      personality, suggesting a clue to relating the personality to a differential
      stress-related psychosomatic trait, although the physiological significance of
      the changes in the low-frequency component range as well as those in the alpha
      frequency component, which are obtained through FFT, should be further clarified.

PMID- 8254988
TI  - [Relationships among physical activity, physical fitness and coronary risk
      factors in adult women--comparison between premenopausal and postmenopausal
      women].
AB  - The relationships among daily physical activity, physical fitness and the risk
      factors for coronary heart disease (CHD) were studied comparing 477 premenopausal
      women (36.1 +/- 7.6 yr) and 178 naturally postmenopausal women (56.7 +/- 5.8 yr).
      The results were as follows. 1) No relationship between physical fitness and
      daily activity level was found in either groups. 2) In premenopausal women, daily
      activity was associated with blood pressure, triglycerides (TG) and blood sugar
      only in the low-fitness group. But there was no relation between risk factors and
      the level of daily activity in the high-fitness group. 3) In postmenopausal
      women, the low-fitness group showed increasing TC/HDLC and decreasing HDLC
      associated with the low daily activity. TC, LDLC and TC/HDLC were lower in the
      high-fitness-with-high-daily-activity group than in the high-fitness-with-low
      daily-activity group. 4) In both groups, the levels of TG and TC/HDLC were lower
      in the high-fitness group than in the low-fitness group. This suggests that serum
      lipids have a closer relation to fitness than to daily activity. These results
      indicate that the relationships among daily activity, physical fitness and CHD
      risk factors are different in menopausal status, and that daily activity is one
      of the most important factors to reduce CHD risk factors, especially in unfit or
      postmenopausal women.

PMID- 8254989
TI  - [Comparison of a rural town and a fishing town: diet and circulatory system
      diseases].
AB  - We report a comparative study of the Standardized Mortality Ratio (SMR) for
      circulatory system diseases and diet in a rural town and a fishing town in Kyoto
      Prefecture. SMR was assessed during the 5-year period from 1983 through 1987, and
      compared with the standard age- and sex-adjusted demographic and mortality
      statistics compiled by the National Census Bureau of Japan in 1985. A food
      frequency questionnaire in which the respondents evaluated their food consumption
      during the previous 1-year period was used to assess diet. The questionnaire was
      administered during February 1989 in the rural town and during February 1990 in
      the fishing town. In comparison with the standard statistics, SMR was higher in
      the rural town and lower in the fishing town. The inhabitants of the fishing town
      more frequently consumed low-fat and low-sodium foods, such as fish, potatoes,
      tofu, and green, yellow and other vegetables, and less frequently consumed high
      fat and high-sodium foods, such as meat, fried food, pickles, than did the
      inhabitants of the rural town. The residents of the fishing town also consumed a
      greater variety of foods in one week. The two towns differ in geography and
      economic structure, and their inhabitants have different life-styles and eating
      habits. The lower SMR for circulatory system diseases in the fishing town may be
      related to the greater consumption of fish and vegetables with lower meat and
      salt intake, as well as the balanced of diet.

PMID- 8254990
TI  - [Analysis of geographical differences in the seasonal variation of mean birth
      weight in Japan (1974-1983)].
AB  - Geographical differences in the seasonal variation in mean birth weight (MBW)
      were examined by a traditional time series analysis based on the birth data of 47
      different prefectures in Japan for the period from January 1974 to December 1983.
      The general pattern on the seasonality in MBW has two peaks in spring and autumn,
      and two troughs in summer and winter. There is a general trend in the seasonality
      with the autumn-peak-dominant pattern observed in the northern part of Japan
      (Hokkaido, Tohoku, Kita-Kanto) giving way to the spring-peak-dominant pattern in
      the southwest. Another interesting finding is that there is high statistical
      significance as a general tendency, in the seasonality among immensely populated
      prefectures such as Tokyo, Kanagawa, Aichi, Osaka, and Fukuoka, while in the case
      of scarcely populated rural prefectures, the time series fluctuates almost
      randomly. Some socio-cultural and biometerological hypotheses were evaluated to
      explain these results.

PMID- 8254992
TI  - [Higher production of tumor necrosis factor (TNF) elicited by a biological
      response modifier (BRM) in aging mice].
AB  - We investigated age-related changes in the capacity for tumor necrosis factor
      (TNF) production in young and aged inbred C3H/He mice by injecting them with OK
      432, a biological response modifier (BRM). An intravenous injection of 0.4mg of
      OK-432 was found to induce TNF production and two consecutive injections of 2KE
      of OK-432 induced much higher TNF production. Both the single and two consecutive
      injections of OK-432 induced significantly higher TNF production in aged mice
      than in young ones. Furthermore, the TNF-productive response to the two
      consecutive injections of OK-432 seemed to increase with aging. Male mice tended
      to show a marginally higher TNF-productive response than females. The mechanism
      by which aged mice have a higher capacity for TNF production is not clear. The
      following possibilities are conceivable. 1) Macrophages which are major TNF
      producer cells may be activated in aged mice. 2) Specific T cells which are cross
      reactive to antigenic determinants in OK-432 may be increased in number in aging
      mice and activate macrophages effectively to produce TNF when stimulated by OK
      432. In general, immunological functions tend to decline with aging. Our present
      results, however, suggest that by using an appropriate BRM we may be able to
      induce higher TNF production in the aged. This might lead to effective prevention
      and therapy for tumors, which increase in incidence with age.

PMID- 8254991
TI  - [Effects of exercise on immune functions in mice].
AB  - This study was carried out to examine the effects of forced running exercise on
      the immune functions of male ICR mice. Mice aged 4 weeks were divided into two
      groups: a non-exercise group (control) and a group given forced running exercise
      (exercise group). The exercise applied was forced running at 15m/min on a flat
      floor without any slope for 60 min a day. The duration of exercise was 5 days per
      week for 12 weeks. The results obtained were as follows: 1) After 12 weeks of
      forced running exercise, the weight of the anterior tibialis muscle and succinate
      dehydrogenase activity in the anterior tibialis muscle increased significantly (p
      < 0.01) in the exercise group compared with the control group. A tendency for
      thymus weight to increase was shown in the exercise group, and liver and spleen
      weights were significantly (p < 0.01) greater than in the control group. 2) The
      potentiation of phagocytic function of the reticulo-endothelial system, examined
      by the carbon clearance method, was seen in the exercise group. 3) The ability of
      peritoneal macrophages (M phi) to phagocytose latex beads significantly increased
      (p < 0.01) in the exercise group. The acid phosphatase activity of peritoneal M
      phi remained in both groups. However, lactate dehydrogenase activity of
      peritoneal M phi significantly increased (p < 0.01) in the exercise group
      compared with the control group. 4) The proliferation of splenocytes induced by
      Con A in the exercise group significantly increased (p < 0.01) compared with the
      control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254993
TI  - Effects of acute exposure to cold on pulmonary arterial blood pressure in awake
      rats.
AB  - This study examined alterations in the degree of exposure to cold and the
      pulmonary arterial pressure in awake, catheter-implanted rats. Seven male Wistar
      rats weighing 280 to 300 g were used. Two special hand-made catheters were
      inserted into the pulmonary artery and the level of the aortic arch,
      respectively. Each animal was exposed once to each of four cold temperatures,
      i.e. 5, 0, -5 and -10 degrees C, and 25 degrees C temperature. Acute cold
      exposures produced significant increases in pulmonary arterial pressure (p <
      0.05). Pulmonary arterial pressure and the ratio of pulmonary arterial pressure
      to systemic arterial pressure increased gradually with exposure to decreasing
      temperatures (p < 0.05). These results indicate the possible significance of
      greater cold exposure in the increased occurrence of high altitude sickness, such
      as high altitude pulmonary edema. Further work is necessary to investigate the
      direct relation between cold-induced pulmonary arterial pressure increments and
      high altitude pulmonary edema.

PMID- 8254994
TI  - [Contents of aluminum and manganese in tea leaves and tea infusions].
AB  - We measured the contents of aluminum and manganese in tea leaves and tea
      infusions by means of various standardized infusion conditions, and by using
      flameless atomic absorption spectrophotometry, and investigated the influence of
      infusion conditions on the elution of aluminum and manganese into the tea
      infusions. Furthermore, we tried to estimate the daily intake of aluminum and
      manganese due to drinking tea infusions. The content of aluminum in tea leaves
      was 1420 micrograms/g in case of wulong tea, 576 micrograms/g in black tea, and
      520 micrograms/g in green tea. The content of manganese was 1440 micrograms/g in
      the case of wulong tea, 670 micrograms/g in green tea, and 535 micrograms/g in
      black tea. The concentration of aluminum in tea infusions was 1.49-5.58
      micrograms/ml in wulong tea, 0.90-4.92 micrograms/ml in green tea, and 0.64-4.35
      micrograms/ml in black tea. The concentration of manganese was 1.75-6.67
      micrograms/ml in green tea, 0.94-4.04 micrograms/ml in wulong tea, and 0.78-3.24
      micrograms/ml in black tea. The ratio of the molar concentration of aluminum to
      that of manganese was 1-2:1 in tea leaves, and 1-5:1 in tea infusions. In the
      case of elevated-temperature infusion, increases of the concentrations of
      aluminum and manganese in tea infusions were recognized. By repeating infusion
      three times according to the standard method for ingredient analysis of food, 18
      29% of the total content of aluminum in tea leaves was eluted, and 12-29% of the
      total content of manganese was eluted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8254995
TI  - [Effects of methyl tertiary-butyl ether on hepatic lipid peroxidation in mice].
AB  - The effect of one-shot or repeated treatment with methyl tertiary-butyl ether
      (MTBE) on lipid peroxidation and cytochrome P-450 in mouse liver was examined.
      One-shot treatment at the 500 mg/kg dose level caused a transient decrease in
      leukocyte number after 24 h. An increased level of lipid peroxide was observed in
      the liver homogenates 24 h after one-shot treatment and four weeks of repeated
      200 mg/kg treatment. The hepatic cytochrome P-450 content increased after one and
      four weeks of repeated treatment (50, 200 mg/kg). On the other hand, the
      treatment did not affect glutathione content and glutathione-S-transferase
      activity. These results indicate that MTBE treatment caused lipid peroxidation in
      the liver homogenate and induction of hepatic microsomal cytochrome P-450
      content.

PMID- 8254996
TI  - The relationship between the ambulatory variability and the laboratory reactivity
      of blood pressure and heart rate.
AB  - We examined the relationship between the ambulatory variability and the
      laboratory reactivity of systolic blood pressure (SBP), diastolic blood pressure
      (DBP) and heart rate (HR) in 21 male college students. The mean increase during
      the waking period from that during sleep was defined as variability 1, and the
      standard deviation of the ambulatory measurements during waking was defined as
      variability 2. The reactivity to laboratory tests was measured by the pretask-to
      task increase in variables. The high SBP variability 1 group showed a
      significantly higher reactivity of SBP and noradrenaline in the bicycle exercise
      test (70w). This suggests the possibility that SBP variability 1, can be
      predicted by increased reactivity to a mild limb exercise test. The high HR
      variability 1 group, and the high SBP variability 2 group showed significantly
      lower reactivity of stroke volume (SV) and cardiac output (CO) in the cold face
      test. Thus, parasympathetic responses such as trigeminal-brainstem-vagal pathway
      function or baroreflex sensitivity seemed to be reduced in these groups. The high
      DBP variability 2 group showed significantly lower DBP reactivity in the cold
      face test, and low noradrenaline reactivity in the mental arithmetic test, which
      indicated a reduced alpha-adrenergic response in this group. No other significant
      differences in reactivity to the laboratory mental stress tests were found
      between the variability 1 and variability 2 groups.

PMID- 8254997
TI  - Characterization of the glomerular endothelial cell in culture.
AB  - Because of difficulties associated with the culture, cloning and propagation of
      glomerular endothelial cells (GENs), the biological properties of these cells
      remain largely unknown. We modified the methods established by Ballermann to
      propagate GENs from adult bovine kidney. We found that the addition of insulin,
      transferrin and selenium into the standard culture media was an important step in
      promoting the propagation of the first clone from a single cell and in
      maintaining the viability of the cells. These cells expressed factor VIII-related
      antigen and took up acetylated-LDL, but did not contain the Weibel-Palade body,
      unlike endothelial cells derived from large vessels. Furthermore, GENs were
      compared with aortic endothelial cells (AECs) to investigate the differences in
      culture conditions. Compared with AECs, GENs required a higher concentration of
      serum and the supplementation of growth factor to maintain their biological
      activity. In addition, GENs were very susceptible to trypsinization and produced
      prostaglandin E2 as a major cyclooxygenase product, whereas AECs produced PGI2.
      These findings suggest that GENs will be easily obtained from adult bovine kidney
      in culture and provide useful information on the functional properties of these
      cells under physiological and pathophysiological conditions.

PMID- 8254998
TI  - Lowered insulin-sensitive Ca2+ transport in cultured glomerular mesangial cells
      from spontaneously hypertensive rats.
AB  - Insulin-resistant state has been postulated in the pathogenesis of hypertension.
      To investigate the role of insulin in Ca2+ regulation of the glomerular mesangial
      cell (MC) in hypertension, the effect of insulin on Ca2+ transport and
      intracellular-free calcium concentration ([Ca2+]i) was measured in serially
      passaged cultured MC obtained from spontaneously hypertensive rats (SHR) and
      Wistar-Kyoto rats (WKY). Insulin produced a substantial increase in 45Ca uptake
      as well as [Ca2+]i in quiescent cultured MC from both strains. These stimulatory
      effects of insulin were completely inhibited by diltiazem, and partially
      inhibited by H-7, TMB-8 and 5-N,N (hexamethylene) amiloride (HMA), but were not
      inhibited by W-7 or trifluoroperazine. Although basal ([Ca2+]i) values were not
      different, insulin-sensitive 45Ca uptake of SHR MC was significantly less than
      that of WKY MC. Insulin-sensitive increase in ([Ca2+]i) of SHR MC was also less
      than that of WKY MC. We concluded that insulin increased 45Ca uptake, leading to
      an increase in ([Ca2+]i), presumably through the voltage-dependent Ca2+ channel,
      intracellular Ca2+ release and/or proteinkinase C-mediated mechanisms in cultured
      MC. Blunted response of insulin-sensitive Ca2+ uptake and ([Ca2+]i) in SHR MC
      suggested differential regulation of Ca2+ transport in response to insulin in the
      kidney with primary hypertension.

PMID- 8254999
TI  - Early and quantitative detection of cisplatin-induced nephrotoxicity by
      measurement of plasma PSP (phenolsulfonphthalein) half-life in rats.
AB  - Renal function following cisplatin injection in rats was assessed by measuring
      the half-life of plasma PSP. Changes in BUN, creatinine, plasma PSP half-life and
      urinary N-acetyl-beta-D-glucosaminidase (NAG) levels were determined in rats
      treated with 6.5 mg/kg i.v. of cisplatin. The highest values of BUN and
      creatinine were both observed on day 5. Half-life of plasma PSP was significantly
      prolonged on days 2 through 5 and reached a peak value on day 3. A significant
      increase in urinary NAG levels appeared on day 2 and the peak value was
      demonstrated on day 3. BUN, creatinine and plasma PSP half-life were also
      determined on days 3 and 5 following several doses of i.v. cisplatin. A dose
      related increase in plasma PSP half-life was observed on day 3, while dose
      related increases in BUN and creatinine levels were found on day 5. The
      evaluation of cisplatin-induced nephrotoxicity by the plasma PSP test was clearly
      superior for early detection compared with conventional renal function tests
      using BUN and creatinine.

PMID- 8255000
TI  - Characteristics of cadmium-induced nephrotoxicity in Syrian hamsters.
AB  - Male Syrian hamsters were used to evaluate cadmium (Cd)-induced nephrotoxicity.
      Furthermore, they were treated with polyaspartic acid (PAA) in an attempt to
      prevent renal damage due to Cd. To induce renal proximal tubular damage, the
      hamsters were administered a single subcutaneous injection of cadmium chloride
      (CdCl2) at the dose of 3 mg/kg body weight. Within 24 hours, they exhibited
      significant proteinuria and an increased urinary excretion of N-acetyl-beta-D
      glucosaminidase (NAG). Renal histological changes consisted of degenerative
      changes in renal tubule cells, irregularly shaped nuclei with marginated
      chromatin and rounded mitochondria. The administration of PAA did not improve
      creatinine clearance or urinary protein excretion. The concentration of Cd in the
      renal tissue showed a gradual increase on day 3 following cadmium exposure.
      Cadmium nephrotoxicity appears to be more severe in Syrian hamsters than in rats
      or mice. Thus, this animal model appears to be excellent for studying Cd-induced
      nephrotoxicity.

PMID- 8255001
TI  - Effects of theophylline, verapamil, and mannitol on oxygen consumption of
      ischemic rat kidneys.
AB  - This study was designed to determine, through the measurement of oxygen
      consumption (QO2), whether pretreatment and posttreatment with theophylline,
      verapamil, and mannitol provide protection from damage in the cortex and medulla
      of rat kidneys subjected to 60 and 120 minutes of ischemia. QO2 levels in both
      tissues were examined 1 day after each ischemia. After 60 minutes of ischemia,
      pretreatment with theophylline and verapamil primarily provided protection from
      ischemic change in cortical QO2. Pretreatment with mannitol provided protection
      from both cortical and medullary changes in QO2, but posttreatment with mannitol
      only protected cortical QO2. After 120 minutes of ischemia, only pretreatment
      with verapamil was effective in protecting cortical QO2 from ischemic injury.
      These observations demonstrate that theophylline, verapamil, and mannitol are
      effective in protecting renal QO2 in the ischemic kidney. During this study, it
      became clear that there were differences in the effectiveness of theophylline and
      verapamil on QO2 in the ischemic kidney between pretreatment and posttreatment,
      and also between the cortex and the medulla.

PMID- 8255002
TI  - Beneficial effects of a non-protein diet on renal function of rats exposed to
      ischemic and nephrotoxic insults.
AB  - We investigated the effects of a non-protein diet on renal recovery in rats
      following 45-minute renal ischemia and mercuric chloride (3 mg/kg BW:S.C.)
      poisoning. The rats were fed a non-protein diet for one week before the renal
      insults. Renal functions were measured 24 hours after renal ischemia or 6 hours
      after mercuric chloride administration. In the ischemia investigation, the
      glomerular filtration rate (GFR), the renal plasma flow rate (RPFR) and the
      percent fractional sodium excretion (%FENa) of rats fed a regular diet (19.6%
      protein) were 25 +/- 7 microliters/min/g KW, 0.19 +/- 0.1 ml/min/g KW and 14.8 +/
      2.0, respectively. These values in the rats fed a non-protein diet showed better
      recovery, returning to a GFR of 114 +/- 32 microliters/min/g KW, an RPFR of 0.37
      +/- 0.1 ml/min/g KW, and a %FENa of 2.43 +/- 0.6, respectively (p < 0.05).
      Furthermore, the seven-day survival rate was improved from 17% in the regular
      diet group to 100% in the non-protein diet group. In the mercuric chloride
      investigation, the renal functions in rats on a regular diet were shown by a GFR
      of 461 +/- 51 microliters/min/g KW, an RPFR of 1.91 +/- 0.2 ml/min/g KW, and a
      %FENa of 2.22 +/- 0.5. One-week feeding with a non-protein diet ameliorated the
      decrease in renal function, resulting in a GFR of 604 +/- 84 microliters/min/g
      KW, an RPFR of 2.15 +/- 0.5 ml/min/g KW, and a %FENa of 2.20 +/- 0.6.
      Consequently, there was a distinct beneficial effect on the survival of these
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255003
TI  - Ultrastructural localization of three major basement membrane components--type IV
      collagen, heparan sulfate proteoglycan and laminin in the normal human GBM.
AB  - Human glomerular basement membrane (GBM) is known to contain type IV collagen,
      heparan sulfate proteoglycan (HS-PG) and laminin in the extracellular matrix. In
      this study, ultrastructural distribution of these antigens was investigated in
      normal human glomeruli using the immunogold technique. Type IV collagen was
      present throughout the GBM, mainly on the lamina densa, and all over the
      mesangial region. HS-PG was present on the laminae rarae, predominantly on the
      lamina rara externa, and periphery of the mesangial region. Laminin was present
      throughout the GBM and peripheral region of the mesangial matrix. Our study
      demonstrated the preferential localization of each component in the GBM.

PMID- 8255004
TI  - Alterations in glomerular extracellular matrix components in glomerulonephritis.
AB  - We investigated alterations in the main components of glomerular extracellular
      matrices, including heparansulfate proteoglycan (HS-PG), laminin, type IV
      collagen and fibronectin in the renal tissues of 61 patients with various types
      of glomerulonephritis. Indirect immunofluorescence stainings with polyclonal
      antibodies of these extracellular matrix components were performed. In minimal
      change nephrotic syndrome, no remarkable changes were observed. In membranous
      glomerulonephritis, non-collagenous components, such as HS-PG and laminin altered
      in distribution, forming spikes in stage II and circles between or around the
      immune deposits in stage III. These changes were observed more clearly in HS-PG
      and laminin than in type IV collagen. These results suggested that non
      collagenous components played an important role in repairing the GBM. In
      membranoproliferative glomerulonephritis and IgA nephropathy, type IV collagen
      and fibronectin expanded in the proliferated mesangial area. These findings
      showed that there was a close relationship between these extracellular matrix and
      the progression of glomerulosclerosis. In dense deposit disease, double contour
      of staining of HS-PG, laminin and type IV collagen was observed along the
      capillary wall. These findings suggested that there were no main extracellular
      matrix components within the dense materials.

PMID- 8255005
TI  - Immunofluorescent analysis of extracellular matrix (ECM) components in glomeruli
      of the hepatic glomerulosclerosis.
AB  - An immunofluorescence study was carried out to evaluate alterations in the
      distribution and/or intensity of extracellular matrix (ECM) components,
      immunoglobulins and complement (C3) in the glomeruli of 7 autopsy patients with
      hepatic glomerulosclerosis. As compared with the findings in normal renal
      tissues, an increase in type IV collagen, laminin and fibronectin was observed in
      expanded glomerular mesangial areas and along glomerular capillary walls.
      Depositions of IgA, mainly IgA1, and C3 in glomeruli were in parallel with those
      of the ECM components. These ECM components were markedly decreased in glomeruli
      showing global sclerosis. In contrast, type I collagen was observed at central
      portions of the sclerotic glomeruli. There was an increase in the type I collagen
      along Bowman's capsules, especially at the sites of capsular adhesion and
      crescent formation. It appears that hyperproduction and/or infiltration of
      glomerular ECM components and interstitial collagen is closely linked to the
      progression of glomerular sclerosis in patients with liver diseases.

PMID- 8255006
TI  - Elevated serum fucose levels in idiopathic nephrotic syndrome.
AB  - We measured serum fucose concentrations in 34 children with idiopathic nephrotic
      syndrome (INS), 23 with chance proteinuria and/or hematuria (CPH), and 20 healthy
      children as controls. The serum fucose levels in the patients with INS were
      significantly elevated at onset (14.0 +/- 3.7 mg/dl, n = 4, p < 0.02), in
      relapses (19.1 +/- 3.7 mg/dl, n = 10, p < 0.001), and in remission (13.9 +/- 7.0
      mg/dl, n = 30, p < 0.01) as compared with CPH patients (10.6 +/- 3.2 mg/dl, n =
      23) and controls (9.1 +/- 3.1 mg/dl, n = 20). Those in remission were further
      divided into 2 groups and the mean fucose concentrations were significantly
      different in the two remission groups: 20.1 +/- 4.6 mg/dl in 14 patients whose
      blood samples were taken within one week of remission and 9.0 +/- 2.9 mg/dl in
      the other 16 patients whose samples were taken at 1 to 6 months of remission. The
      mean value in the latter remission group was significantly lower in comparison
      with the former group, but not different from the controls. Gel-chromatography of
      serum samples from patients with INS revealed a single peak of fucose in the high
      molecular fraction, and this was also found in the same fractions of serum
      inhibitor of lymphocyte blastogenesis in INS. We concluded that serum fucose
      concentrations are elevated in INS patients and that, because of the large
      molecular weight, the fucose is probably in a form bounded to some glycoproteins
      in the serum. Considering various reports on fucose, serum fucose may be
      associated with immunodepression in INS patients.

PMID- 8255007
TI  - Effect of the angiotensin converting enzyme inhibitor, captopril, on proteinuria
      in chronic glomerular disease.
AB  - The antiproteinuric effect of the angiotensin-I-converting enzyme inhibitor,
      captopril, was studied in 14 patients (10 men and 4 women, age range of 24 to 60
      years) with chronic glomerulonephritis in whom IgA nephritis had been confirmed
      by renal biopsy. Eight of the 14 patients had received antihypertensive drugs
      such as calcium channel blockers, diuretics or beta-blockers. Captopril was added
      to these regimens at 25 mg twice daily in 3 patients, and 37.5 mg in 11 patients.
      Proteinuria decreased from 2.55 +/- 0.48 g/day to 1.58 +/- 0.35 g/day within
      three months after the start of administration. In 4 patients (28.6%), the extent
      of reduction was over 50%, and in 8 patients (57.1%), over 25%. Blood pressure,
      creatinine clearance and serum creatinine were not changed significantly. There
      was a positive linear correlation between the extent of reduction of proteinuria
      and the increase in plasma renin activity (r = 0.93, p < 0.001). We conclude that
      captopril reduces proteinuria in some patients with IgA nephritis whose plasma
      renin activity responds to the drug.

PMID- 8255008
TI  - Early intensive therapy for clinical remission of active IgA nephropathy: a three
      year follow-up study.
AB  - To achieve clinical remission, intensive therapy in active IgA nephropathy was
      conducted on a trial basis. Forty-five patients with active IgAN in which
      cellular crescents were present were divided into two groups. The patients in one
      group (Group A, N = 19) were treated with a combined regimen of steroid pulse,
      cyclophosphamide (4 months), dipyridamole (36 months) and warfarin. The patients
      in the other group (Group B, N = 26) were treated with tonsillectomy in addition
      to the same regimen as Group A. Three years after the initiation of treatment,
      proteinuria and hematuria had significantly decreased in both groups, and the
      renal function in Group B was significantly improved. Remission of proteinuria
      and hematuria was achieved in five patients (26.3%) and eight patients (42.1%),
      respectively, in Group A, and 14 patients (53.8%) and 20 patients (76.9%),
      respectively, in Group B. These results indicate that early intensive therapy
      combined with tonsillectomy in active IgAN is potentially of great benefit from
      both the medical and socioeconomic points of view.

PMID- 8255009
TI  - Effects of high-dose vitamin B6 therapy on microcytic and hypochromic anemia in
      hemodialysis patients.
AB  - In an attempt to treat hemodialysis patients suffering from microscopic and
      hypochromic anemia (MHA) and who are either sufficient or deficient in serum
      ferritin level, we investigated the effects of oral administration of vitamin B6
      (VB6). Twenty-six patients with MHA undergoing long-term stable hemodialysis
      treatment were divided into three groups. There was no significant difference in
      the serum VB6 levels in these patients as compared with normal subjects before
      the study. Patients in group I, whose serum ferritin levels were normal, were
      orally administered 180mg of VB6 every day for 20 weeks. Patients in groups II
      and III, whose serum ferritin levels were far below normal (due to suspected iron
      deficiency anemia), were either administered iron alone (intravenous
      administration of 40mg of iron for 12 consecutive dialysis treatments, for 4
      weeks--group II) or both iron and VB6 (group III). There was significant
      improvement in the hematocrit, mean corpsular volume (MCV), and mean corpsular
      hemoglobin (MCH) in group I patients supporting the contention that this group of
      patients had pyridoxine responsive anemia (PRA). The number of sideroblasts in
      bone marrow in these patients, however, was significantly low when compared to
      that of the normal subjects. In addition, the combined therapy with iron and VB6
      led to the longer-sustained improvement in hematocrit in patients with suspected
      iron deficiency anemia (group III) when compared to those treated with iron alone
      (group II).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255010
TI  - Effect of recombinant human erythropoietin administration on immunological
      indices in patients undergoing chronic hemodialysis.
AB  - In patients undergoing chronic hemodialysis, marked anemia may cause decreased
      immunological function. To improve this anemia, we investigated the effect on
      immunological indices of recombinant human erythropoietin (rHuEPO) administration
      in 24 hemodialysis patients (13 males and 11 females) with renal anemia
      complications. Their mean age was 54.9 +/- 14.8 years and the mean duration of
      dialysis was 100.5 +/- 54.9 months. The subjects were treated with rHuEPO for 12
      months, which helped to maintain a hematocrit value elevated by 5% from the
      baseline. Cell-mediated immunity and humoral immunity were assessed prior to as
      well as throughout the treatment period. Of the total number of patients studied,
      the anemia of 16 improved while 8 did not show signs of sufficient improvement.
      The improved group showed an increase in in vitro lymphocytic response to
      phytohemagglutinin (PHA), CD4/CD8, CD16 and serum IgM levels, while the CD8 level
      decreased significantly. Improvement in the general physical condition with
      rHuEPO treatment appeared to be associated with the changes in immunological
      indices, but the precise mechanism remains obscure.

PMID- 8255011
TI  - Effects of recombinant human erythropoietin (EPOCH) on the coagulation and
      fibrinolytic systems and platelet function in pre-dialysis patients with chronic
      renal failure.
AB  - The purpose of this study was to investigate whether or not the systems of
      coagulation and fibrinolysis are activated after human recombinant erythropoietin
      therapy in patients with end-stage renal failure and renal anemia. Six thousand
      IU of human recombinant erythropoietin (EPOCH) were administered intravenously to
      11 patients once a week for 8 weeks. Coagulation, fibrinolysis and platelet as
      well as renal functions were investigated before and after the EPOCH therapy.
      Platelet count did not increase in spite of improvement in anemia. No changes in
      prothrombin time, activated partial thromboplastin time, concentrations of
      fibrinogen, fibrinopeptide A, thrombin antithrombin III complex,
      fibrin/fibrinogen degradation products (FDP), FDP-E, FDP-D dimer, plasmin alpha 2
      plasmin inhibitor complex were observed. Platelet factor 4 and beta
      thromboglobulin also were unchanged. Reciprocal changes in serum creatinine
      concentrations over the duration of therapy were compared before and after
      therapy. There was no significant difference between the reciprocal changes in
      serum creatinine concentrations before and after therapy. The increases in
      hemoglobin did not correlate with the changes in coagulation, fibrinolysis and
      the other parameters, except for the change in prothrombin time. These results
      indicate that coagulation, fibrinolysis and platelet systems in end-stage renal
      failure patients were not affected by EPOCH administration, in spite of increase
      in hemoglobin.

PMID- 8255012
TI  - Effects of long-term, low-fat diet on plasma apo E in familial LCAT deficiency.
AB  - To study the metabolic abnormalities in familial lecithin-cholesterol
      acyltransferase (LCAT) deficiency, the effects of a long-term, low-fat diet and
      LCAT replacement therapy on plasma lipids and apolipoproteins were investigated
      in a patient with LCAT deficiency. The patient had elevated triglycerides (TG,
      543.7 mg/dl) and phospholipids (PL, 350.3 mg/dl) and normal total cholesterol
      (TC, 206.9 mg/dl). Change to a low-fat diet reduced TC and TG by 20% and 75%,
      respectively. These reductions occurred mainly in the d < 1.006 fraction. At
      baseline, the patient had normal apolipoprotein B (apo B), low apolipoprotein A-I
      (apoA-I) and apolipoprotein A-II (apoA-II) and elevated apolipoprotein E (apo E).
      Long-term treatment with a low-fat diet increased plasma apoA-I and decreased apo
      E. However, urinary protein excretion did not change throughout the observed
      period. LCAT replacement with fresh frozen plasma (FFP) after the low-fat diet
      further reduced plasma apo E to the normal range. These results indicate that the
      elevated plasma apo E in LCAT deficiency was related not only to the lack of LCAT
      in the plasma, but also to fat intake. A low-fat diet may be effective in
      correcting lipid abnormalities. Moreover, plasma apo E may be a good indicator of
      the efficacy of diet therapy.

PMID- 8255013
TI  - [Pathogenesis of development of lung cancer in idiopathic interstitial pneumonia-
      growth factors in bronchoalveolar lavage fluid].
AB  - It has been generally accepted that lung fibrosis as in idiopathic interstitial
      pneumonia (IIP) is frequently associated with the development of lung cancer.
      This observation implies that the mechanism involved in carcinogenesis and/or
      enhanced proliferation of cancer cells is common to the fibrosing process.
      However, there are few studies reported on the pathogenesis of associated lung
      cancer except for several studies assessed from the point of view of surgical
      pathology. This study was undertaken to learn whether BAL fluid, which reflects
      the local milieu of the fibrosing process, enhances the proliferation of human
      lung cancer cell line Lu-99, Lu-65 and rat lung fibroblasts as assessed by 3H
      thymidine incorporation. BAL fluid was obtained from patients with IIP (n = 8)
      and normal volunteers (n = 8). BAL fluids from patients with IIP enhanced the
      mean incorporation of 3H-thymidine of Lu-99 up to 3.6 times (p < 0.01) compared
      to that of normal volunteers. Furthermore, the mean incorporation of Lu-65 was
      increased up to 1.8 times (p < 0.05) by BAL fluids from patients with IIP. In
      contrast, BAL fluids from patients caused no significant increase of the mean
      incorporation of rat lung fibroblasts as compared to normal BAL fluids. The
      enhancing activities on the growth of cancer cell line Lu-99, Lu-65 were eluted
      in several fractions by high performance liquid chromatography using Superose 12.
      These observations indicate that the BAL fluid of IIP patients contains factors
      enhancing the growth of cancer cells.

PMID- 8255014
TI  - [Differential detection of IL-1 beta and TNF-alpha mRNA on lung macrophages from
      patients with pulmonary sarcoidosis].
AB  - In pulmonary sarcoidosis or experimental granuloma formation, interleukin-1 beta
      (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha) are considered to play
      important roles during inflammatory evolution. In order to examine whether IL-1
      beta or TNF-alpha mRNA expression on lung macrophages relates to the disease
      activity or clinical course, ten cases with pulmonary sarcoidosis were divided
      into two groups: five cases who had a disease duration of more than 10 years
      (14.6 +/- 4.4 years; group A), and 5 cases with duration of less than 3 years
      (1.7 +/- 1.1 years; group B). All cases showed both abnormal radiographs and
      elevated serum angiotensin converting enzyme activities. We compared the 10 cases
      with 12 healthy individuals as normal control (6 nonsmokers: NS and 6 current
      smokers: S), and 5 cases with idiopathic pulmonary fibrosis (IPF) as disease
      control. Lavage macrophages were purified by rosette forming method and plastic
      adhesion was then performed for 1 hour. Thereafter mRNA was extracted by AGPC
      method and amplified by reverse transcriptase-polymerase chain reaction (RT-PCR)
      (20 cycles). The results showed that IL-1 beta mRNA was detected in all materials
      studied, but TNF-alpha mRNA expression was different among the groups: 5/5 (100%)
      in group A, 1/5 (25%) in group B, 5/5 (100%) in IPF, and 12/12 (100%) in normal
      controls. The absence of detection of TNF-alpha mRNA (rapid down regulation) in
      pulmonary sarcoidosis may relate to spontaneous regression, because a substantial
      number of cases in group B showed spontaneous regression in their natural
      course.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255015
TI  - [Clinicopathological study of 10 cases of Pneumocystis carinii pneumonia].
AB  - A retrospective study was conducted to evaluate the prognostic factors in
      patients with Pneumocystis carinii pneumonia (PCP). From 1976 through 1991, a
      total of 10 PCP cases were pathologically diagnosed of our hospital. All patients
      were immunocompromised hosts treated with corticosteroids and/or cytotoxic drugs
      for their underlying diseases of malignancy in 6 and autoimmune disease in 4. The
      frequent symptoms in the early stage of PCP were fever in 9 and dry cough in 4
      patients. The chest X-ray exhibited bilateral diffuse infiltrates in all
      patients. In 3 patients, the infiltrates which were localized at the early stage
      progressed rapidly to both lungs in a few days. All of the 3 patients in 1970-79
      were diagnosed by autopsy without effective treatment. Four of the 5 patients in
      1980-89 were diagnosed by autopsy or necropsy and one patient was diagnosed by
      transbronchial lung biopsy (TBLB). All the 5 patients in 1980-89, including 3
      patients treated with sulfamethoxazole and trimethoprim (ST), died. Two patients
      in 1990-93 who were diagnosed by examination of TBLB or sputum specimen recovered
      from PCP following treatment with ST. These results indicate that the early
      diagnosis of PCP by the development of diagnostic techniques followed by
      effective treatment with anti-PCP drugs has greatly improved the outcome of PCP.

PMID- 8255016
TI  - [Evaluation of the elastase burden in patients with idiopathic interstitial
      pneumonia].
AB  - This study was designed to clarify the role of neutrophil elastase in the
      pathogenesis of idiopathic interstitial pneumonia (IIP). To accomplish this,
      elastase: alpha 1-antitrypsin complexes in plasma and bronchoalveolar lavage
      fluids (BALF) were measured in 19 patients with IIP and compared to 15 normal
      smokers. Cell differentiation counts showed that there was no difference in
      percent neutrophils in BALF between IIP patients and normal smokers. However,
      elastase: alpha 1-antitrypsin complexes were significantly increased in both
      plasma and BALF in patients with IIP compared to normal smokers. In IIP patients
      with honeycombing demonstrated by high resolution CT, although elastase: alpha 1
      antitrypsin complexes were not significantly increased in plasma, elastase: alpha
      antitrypsin complexes in BALF were significantly increased compared to IIP
      patients without honeycombing. Western immunoblot analysis showed that although
      the native 80-KD elastase: alpha-antitrypsin complex was detected in BALF, the
      molecular weight of elastase: alpha 1-antitrypsin complex in plasma was 60-KD.

PMID- 8255018
TI  - [Study of uneven pulmonary ventilation by sequential bolus method].
AB  - We report a new method of measuring the sequential ventilation associated with
      the primary mechanism for ventilation inhomogeneity. Four types of sequential
      curves were examined using simultaneous washouts of multiple tracer boluses
      inhaled from residual volume (RV) and at volumes above RV. The factors that
      affected the classification of curves were analyzed by the theory of
      quantification from the statistical data of blood gases, lung function tests, X
      ray and clinical diagnosis. This method was applied to evaluate the ventilation
      distribution in 100 patients with pulmonary disease. It provided clinical
      information on certain types of disease which cannot be detected by traditional
      lung function tests. Sequential bolus method may permit determination of whether
      the disease has predominantly intra or inter-regional inhomogeneity.

PMID- 8255017
TI  - [Effects of aerosol oxitropium bromide and fenoterol on maximal exercise capacity
      in chronic obstructive pulmonary disease and their correlation with air flow
      during exercise and with parameters of maximal exercise].
AB  - To examine the effects of bronchodilators on maximal exercise capacity and their
      correlation with airflow during exercise in patients with chronic obstructive
      pulmonary disease (COPD), we conducted a double-blind, randomized comparison
      between inhaled fenoterol (beta 2-agonist) and oxitropium bromide
      (anticholinergic agent) in 8 patients with stable COPD (mean age 73 years, mean
      FEV1 1.1 L, mean FEV1% 50%). Only oxitropium bromide resulted in statistically
      significant improvement in FEV1 40 min after inhalation. On maximal exercise,
      fenoterol did not affect oxygen uptake (VO2 max), minute ventilation (VEmax),
      respiratory frequency (Rfmax), ventilatory efficacy (VEmax/VO2 max), peak
      expiratory flow during exercise (PEFmax), heart rate (HRmax) and dyspnea (Borg
      Scale Slope). After oxitropium bromide, dyspnea during exercise and HRmax
      decreased significantly, but PEFmax and other parameters did not change
      significantly compared with control. There was no correlation between changes in
      dyspnea during exercise and changes in FEV1 and PEFmax after oxitropium bromide
      inhalation. We conclude that inhaled oxitropium bromide, an anticholinergic
      agent, reduces dyspnea during exercise in patients with COPD. This favorable
      effect was not due to change of airflow limitation during exercise, and other
      factors can thus influence reduction of dyspnea during exercise in these
      patients.

PMID- 8255019
TI  - [Traffic accidents in obstructive sleep apnea patients and effect of nasal CPAP
      treatment].
AB  - We studied the traffic accident rates and daytime sleepiness in obstructive sleep
      apnea syndrome (OSAS) patient, and evaluated the effectiveness of long-term nasal
      CPAP treatment. Traffic accidents were observed in 42% of 14 male OSAS patients
      (46 +/- 7 years old) and near-miss accidents were also observed in 64% during the
      past three years. Stanford Sleepiness Scale showed 4.7 +/- 1.0, suggesting marked
      excessive daytime sleepiness (EDS). During NCPAP treatment for 11 +/- 9 months,
      no traffic and near-miss accidents were reported. After NCPAP treatment, SSS
      decreased to 2.0 +/- 0.8, and the score of Uchida-Kraeplin test for the
      evaluation of working ability increased significantly. These results suggest the
      improvement of EDS and working ability following NCPAP treatment. We conclude
      that OSAS patients have the tendency of daytime sleepiness and high traffic
      accidents rates, and NCPAP treatment is effective to improve such problems.

PMID- 8255020
TI  - [Early detection of chronic obstructive pulmonary disease by following individual
      annual changes in lung function].
AB  - The possibility of early detection of chronic obstructive pulmonary disease
      (COPD) was investigated among subjects whose lung function could be followed for
      more than ten years. Ten subjects aged 60 or more were selected from among about
      1500 cases using the following diagnostic criteria; (1) subjects had complained
      of exertional dyspnea (2) chest X-ray abnormalities were suggestive of COPD (3)
      FEV1.0% was under 55%. Data on FVC/height, FEV1.0/height and FEV1.0% of these
      subjects were available for the previous ten years. Individual linear regression
      equations were estimated. Average annual changes of cases of obstruction were
      compared with those of normal cases, and individual deviations from the normal
      standard range were observed. Declines of the regression lines were as follows;
      FEV1.0/height: normal case--0.016 +/- 0.017, obstruction cases--0.038 +/- 0.018
      (L/m/yr), FEV1.0%: normal cases 0.164 +/- 0.627, obstruction cases--1.522 +/-
      0.638 (%/yr). Significant differences were observed between the normal and the
      obstruction cases (p < 0.01). FEV1.0% of all obstruction cases was under--2 SD of
      that of normal subjects. All individual FEV1.0% regression lines of the
      obstruction cases were outside +/- 2 RSD of the normal standard range more than 5
      years before the onset of symptoms. Following individual annual changes in lung
      function was considered to be useful for the early detection of COPD.

PMID- 8255021
TI  - [Roles of serotonin in glass-bead pulmonary microemboli].
AB  - We investigated the role of serotonin release from aggregating platelets in glass
      bead microemboli on isolated perfused rabbit lungs. The perfusion was performed
      at 70 ml/min with a roller pump. The temperature of the perfusion circuit was
      maintained at 37 +/- 1 degrees C by means of a heat exchanger. 100 microns
      diameter glass beads (1 g) were infused via the main pulmonary artery. We
      examined the concentration of serotonin and the number of platelets in the
      perfusate and the mean pulmonary arterial pressure before and after glass bead
      embolization. Administration of PRP (platelet-rich plasma) to the perfusate
      caused the concentration of serotonin to significantly increase after
      microembolization. Specific serotonin S2 receptor antagonist (DV-7028) inhibited
      the increase of serotonin concentration in the perfusate, platelet aggregation,
      and vasoconstriction. We concluded that in the glass-bead embolization model,
      serotonin was released from aggregating platelets surrounding the glass beads,
      and constricted pulmonary microvessels via serotonin S2 receptors on the vascular
      smooth muscles cells.

PMID- 8255022
TI  - [Study of pathophysiology of pulmonary circulation in polycythemia using
      scintigraphy].
AB  - In order to evaluate the pathophysiology of pulmonary circulation in
      polycythemia, Tl-201 myocardial scintigraphy and perfusion lung scintigraphy with
      99m-Tc MAA were performed in 19 cases with polycythemia including polycythemia
      rubra vera and in 11 cases with secondary polycythemia due to pulmonary diseases.
      Tl-201 lung uptake, right ventricular visualization and pulmonary perfusion
      impairment were studied. In the 19 cases, Tl-201 lung uptake was observed in all
      cases and 54.5% of them showed moderate lung uptake. The grade of right
      ventricular visualization was moderate in one case and slight in 16 cases; right
      ventricular hypertrophy was shown in 89.5% of all cases by Tl-201 scintigraphy,
      only one of which showed right ventricular hypertrophy on electrocardiography.
      Abnormalities of lung perfusion consisted of scattered small areas of
      hypoperfusion in 36.8%, peripheral hypoperfusion in 78.9% and uneven distribution
      of pulmonary perfusion in 94.7%. The degree of hypoperfusion was slightly related
      to decrease in FEV1.0%, V25 and PaO2 and increase in circulating blood volume and
      peripheral red blood cell counts. Abnormalities of pulmonary function consisted
      of increased RV/TLC in 50.0%, increased CV/VC in 35.7% and decreased V25 in
      36.8%. Arterial blood gases showed hypoxemia in 57.1%, the degree of which was
      slightly related to increase in RV/TLC and CV/VC and decrease in V25. Cases of
      secondary polycythemia due to pulmonary diseases showed more marked right
      ventricular visualization, pulmonary perfusion impairment and abnormalities of
      various kinds of pulmonary function than polycythemia rubra vera cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8255023
TI  - [Clinical features of measles pneumonia in adults: usefulness of computed
      tomography].
AB  - The clinical features, chest radiographs and computed tomographic (CT) images
      were evaluated in 11 cases with serologically proved adult measles complicated
      with pneumonia (10 were previously healthy and one had sarcoidosis). Pneumonia
      appeared during the rash period in all cases. Respiratory symptoms were cough
      (9/11), dyspnea (3/11), and hypoxemia (10/11). Pneumonia manifestations were
      detected in only 4 cases by chest radiograph; on the other hand, they were seen
      in all cases by CT scan and consisted of ground-glass opacities (73%), nodular
      opacities (64%) and consolidation (27%). CT seems to be a useful method to detect
      measles pneumonia if it is suspected. Measles pneumonia in previously healthy
      patients had a good prognosis, as the hypoxemia disappeared within 6 days in all
      cases. The sarcoidosis patient showed prolonged pneumonic shadows and period of
      hypoxemia. Measles pneumonia occurring in a host with cellular immunodeficiency
      may have a severe clinical course.

PMID- 8255024
TI  - [A case of bronchial lipoma treated by Nd-YAG laser surgery].
AB  - A 59-year-old man was referred to our hospital with complaint of cough. On
      physical examination the patient was 159 cm tall and weighted 68 kg. Chest X-ray
      showed an infiltrative shadow in the left lower lung field. Bronchoscopic
      findings revealed a polypoid tumor with smooth surface, located at the lower part
      of the left main bronchus and occupying over two-thirds of the left basal
      bronchus. A hamartoma was suspected as the result of bronchial biopsy. Endoscopic
      Nd-YAG laser surgery was performed. The left basal bronchus was opened.
      Histologically the tumor consisted mainly of mature fat tissue with collagen
      fibers and was diagnosed as a bronchial lipoma. Bronchial lipoma arising from the
      submucosal tissue of a large bronchus, occurs mainly in obese and middle-aged
      men. It is a rare benign tumor of the lung and only 38 cases have been reported
      in Japan.

PMID- 8255025
TI  - [Adult respiratory distress syndrome due to sepsis caused by Staphylococcus
      aureus: a case report].
AB  - A 59-year-old man, under treatment for osteoarthritis of the right hip joint, was
      admitted to the Department of Orthopedic Surgery of Health Insurance Nankai
      Hospital with complaints of high fever and severe right hip joint pain. Since he
      developed shock, he was transferred to the Department of Internal Medicine. The
      laboratory data showed marked increase of acute phase reactants, and
      Staphylococcus aureus was cultured from the abscess in the right hip joint. The
      chest X-ray film the next day showed diffuse pulmonary edema of both lungs. The
      diagnosis of adult respiratory distress syndrome (ARDS) due to sepsis caused by
      S. aureus was made. Septic ARDS due to S. aureus is rare. The patient was cured
      by mechanical ventilation and administration of antibiotics, methyl-prednisolone
      and Urinastatin, along with drainage of the abscess in the right hip joint.

PMID- 8255026
TI  - [A case of pulmonary lymphangiomyomatosis treated with bilateral oophorectomy and
      methyl-progesterone-acetate].
AB  - A case of pulmonary lymphangiomyomatosis is reported. A 37-year-old woman was
      admitted with hemosputum and dyspnea on exertion. Chest roentgenogram revealed
      diffuse reticulonodular shadows and arterial hypoxemia was present. Pulmonary
      function tests showed severe restrictive & obstructive impairment, and pulmonary
      perfusion scintigraphy with 99mTc-MAA showed non-segmental disproportion. The
      histological diagnosis of pulmonary lymphangiomyomatosis was made by
      transbronchial lung biopsy. She underwent bilateral oophorectomy under general
      anesthesia. However, the arterial hypoxemia advanced gradually, and
      medroxyprogesterone-acetate (MPA) was commenced (200 mg/day). Her condition
      remained stable after the description of MPA.

PMID- 8255027
TI  - [A case of spontaneous remission of paragonimiasis miyazakii].
AB  - A 52-year-old man was admitted with fever and chest pain. Chest X-ray showed a
      soft infiltration in the right lung and bilateral pleural effusions. A strong
      tuberculin reaction was elicited. Significant laboratory findings included
      eosinophilia (37% in peripheral blood and 78% in pleural fluid) and elevated IgE
      levels (577 IU/ml in sera and 6700 IU/ml in pleural fluid). Adenosine deaminase
      activity in the pleural fluid was high. No helminth eggs were detected after
      repeated examination of the pleural fluid and sputum. No definitive diagnosis was
      made. Three months of chemotherapy with INH and rifampicin resulted in little
      improvement. Corticosteroid was then administered orally under a tentative
      diagnosis of idiopathic eosinophilic pleurisy, which proved to be a successful
      treatment and resulted in a marked reduction of pleural fluid volume. Two years
      after discharge, the patient's chest X-ray was normal and laboratory findings
      were normal including the eosinophil count and IgE level. The pleural fluid
      obtained at the first admission and kept frozen was subjected to immunological
      analysis for anti-parasite antibody activity. The pleural fluid showed an
      unexpectedly high titer of antibody activity (x6400 dilution) against Paragonimus
      miyazakii antigen assayed by double diffusion Ouchterlony method. Examination of
      the sera obtained from the patient two years after discharge, however, revealed
      no detectable antibody activity against the parasite antigens assayed either by
      Ouchterlony or ELISA method. We concluded from the clinical as well as laboratory
      findings that the patient had recovered from Paragonimiasis miyazakii without
      specific intervention for the disease.

PMID- 8255029
TI  - [A case of sho-saiko-to-induced pneumonitis, diagnosed by lymphocyte stimulation
      test using bronchoalveolar lavage fluid].
AB  - A 66-year-old Japanese man was admitted to our hospital with fever, cough and
      dyspnea. He had been taking Sho-Saiko-to, a traditional Chinese medicine, for
      twenty days. On admission, chest X-ray examination revealed a reticular pattern
      in the bilateral lungs, and respiratory failure was evident. Serum levels of CRP
      and LDH were elevated. A differential cell count of the bronchoalveolar lavage
      fluid (BALF) showed that lymphocytes and eosinophils were increased. Alveolitis
      with lymphocyte and plasma cell infiltration was observed in a pathological
      specimen obtained by transbronchial lung biopsy. After all drugs had been
      discontinued, PaO2, serum CRP and serum LDH improved, and the reticular pattern
      in the bilateral lungs gradually resolved without administration of
      corticosteroids or antibiotics. A lymphocyte stimulation test for Sho-Saiko-to
      using BALF gave a positive result, although LST using blood gave a doubtful
      reaction. The diagnosis of Sho-Saiko-to-induced pneumonitis was made from the
      clinical course, laboratory findings, BALF cell analysis, pathological findings
      and LST using BALF. Only 13 cases of pneumonitis due to administration of
      traditional Chinese medical drugs have been reported. This case suggests that LST
      using BALF is useful for the diagnosis of drug-induced pneumonitis.

PMID- 8255028
TI  - [Two cases of pulmonary lymphangioleiomyomatosis].
AB  - We report two cases of pulmonary lymphangioleiomyomatosis with recurrent
      spontaneous pneumothorax. The cases were diagnosed by open lung biopsy. Case 1
      was a 38-year-old woman, whose chest X-ray showed linear and reticular shadows.
      Lung tissue was negative for hormone receptors. She was treated with tamoxifen,
      but developed allergic symptoms. Her condition gradually deteriorated despite
      oxygen and progesterone therapy. Case 2 was a 41-year-old woman, whose chest X
      ray showed a reticular shadows and slight overinflation. Hormone receptors were
      not examined, but the disease did not progress with oxygen, progesterone and GnRH
      agonist (Sprecur) therapy.

PMID- 8255030
TI  - [A case of bronchogenic squamous cell carcinoma associated with Swyer-James
      syndrome].
AB  - Swyer-James syndrome is considered to be a relatively uncommon disease entity
      presenting with unilateral hyperlucent lung due to hypoplasia of a pulmonary
      artery and bronchiectasis of the affected lung. Association of bronchogenic
      carcinoma with Swyer-James syndrome has not apparently been reported in any
      previous literature, except for one Japanese case. In the present paper, we
      describe a 48-year-old male individual, who developed poorly differentiated
      squamous cell carcinoma of the right upper lobe bronchus after he had been
      diagnosed to have Swyer-James syndrome with unilateral hyperradiancy of the left
      lung. It is suggested that the bronchial epithelium of the unaffected lung in
      Swyer-James syndrome is likely to be more exposed to extrinsic carcinogens than
      that of the affected, underventilated lung, hence resulting in a higher risk of
      developing bronchogenic carcinoma.

PMID- 8255031
TI  - [A case of post-traumatic eosinophilic pleural effusion improved by direct
      infusion of corticosteroid into the pleural space].
AB  - A 49-year-old man was admitted with non-productive cough and left chest
      discomfort. About one month prior to the admission, he suffered a non-penetrating
      injury to the left anterior chest. Although rib fracture or pleural effusion was
      not reported, left chest discomfort and non-productive cough progressed
      gradually. Chest X-ray film and chest CT scan on admission showed left massive
      pleural effusion. Close examination revealed a marked increase of eosinophils in
      the pleural effusion (77% of total cell counts). Because malignancy, parasitic
      disease, and collagen disease were differentiated, we diagnosed this case as post
      traumatic eosinophilic pleural effusion, and decided to administers
      corticosteroid therapy; hydrocortisone 300 mg was infused into the left pleural
      space. Seven days after the treatment, the pleural effusion and peripheral
      eosinophilia had completely disappeared. This case suggests that direct infusion
      of corticosteroid into the pleural space provides greater drug availability in
      the treatment of post-traumatic eosinophilic pleural effusion related to
      immunological reaction of the pleura. The indication and dosage of
      corticosteroids should be established, however, because there have been some
      reports of cases of improvement without any special treatment.

PMID- 8255032
TI  - [A case of chronic necrotizing pulmonary aspergillosis treated with
      itraconazole].
AB  - An 84-year-old woman was admitted because of fever, hemoptysis and productive
      cough with infiltrative shadows in the right lung field on chest X-ray. Chronic
      necrotizing pulmonary aspergillosis was diagnosed on the basis of her clinical
      and radiographic features, positive cultures and positive serological tests.
      Conventional chemotherapy with fluconazole and 5-FC produced only minimal
      improvement. A course of itraconazole was initiated and proved to be effective.

PMID- 8255033
TI  - [Mediastinal abscess due to endotracheal intubation].
AB  - A 38-year-old woman was brought to hospital in an unconscious condition due to
      hypoglycemic coma. At 23 years of age she was diagnosed as having insulin
      dependent diabetes mellitus. She had been treated with insulin but the control of
      her blood sugar was inadequate. Emergency endotracheal intubation was performed
      and she began to breathe spontaneously. Two days later, sore throat, swelling of
      the neck and fever appeared. She was therefore transferred to our hospital. CT
      showed a continuous abscess with multiple air bubble from the pharynx to the
      mediastinum. Cervical incision was performed and treatment with ampicillin,
      cefmetazole, and clyndamicin was started. Culture of the pus revealed alpha
      streptococcus. The abscess decreased in size and her blood sugar was controlled
      by insulin and diet. She was discharged after 11 weeks of hospitalization. At
      that time CT showed only emphysematous change.

PMID- 8255034
TI  - [Surgical treatment of tuberculous abscess in chest wall].
AB  - A case of chest wall tuberculosis with empyema is reported. A 45-year-old woman
      with a history of right lung pleuritis was admitted to our hospital with right
      shoulder pain. The chest X-ray film showed abnormal shadow in the right lower
      lung field. Chest CT revealed right posterior chest wall abscess and localized
      empyema. Bacterial examination of the chest wall abscess obtained by needle
      aspiration biopsy disclosed positive acid-fast bacilli. Three months after
      starting antituberculous therapy with INH, RFP and SM, the chest wall abscess had
      been increased and abscess drainage was performed. After two months of tube
      drainage, the abscess was diminished in size and enucleation with primary closure
      was performed. Antituberculous chemotherapy was continued. One year after
      surgery, no sign of recurrence was observed and the residual empyema was
      decreased.

PMID- 8255035
TI  - [A case of rheumatoid arthritis with obstructive bronchiolitis appearing after D
      penicillamine therapy].
AB  - A 56-year-old woman was diagnosed as having rheumatoid arthritis in 1983. She was
      treated with D-penicillamine in addition to non-steroid anti-inflammatory drugs
      from April 1990. In August she noticed shortness of breath on exertion. Chest X
      ray films showed bilateral interstitial shadows, and chest CT revealed bilateral
      multiple wedge-shaped shadows extending distally. Blood gas analysis showed
      severe hypoxemia and pulmonary function tests demonstrated decreased %VC, FEV1.0%
      and diffusion capacity. Open lung biopsy specimens revealed infiltration of
      inflammatory cells and fibrotic change in the walls of bronchioles. She was
      diagnosed as having obstructive bronchiolitis. Corticosteroid therapy and
      discontinuation of D-penicillamine therapy stopped the progression of her
      symptoms, and she was discharged on corticosteroid maintenance treatment and home
      oxygen therapy.

PMID- 8255036
TI  - [A case of idiopathic thrombocytopenic purpura associated with eosinophilic
      pneumonia with unusual shadows].
AB  - A 31-year-old woman who had been diagnosed as having idiopathic thrombocytopenic
      purpura at her first delivery (July, 1991) was admitted to our hospital on 17
      July, 1992 for dry cough and abnormal chest shadow. Chest CT showed a hemisphere
      like shadow in the left upper lung field. The TBLB specimen showed a mild
      eosinophilic pneumonia. When the patient was observed without medications, a ring
      like shadow appeared newly in the right middle field and the both shadows became
      gradually wider and lighter. Cases of eosinophilic pneumonia showing such shadows
      are considered to be very rare and interesting.

PMID- 8255037
TI  - [Mullerian inhibiting substance].

PMID- 8255039
TI  - [Determination of oxalic acid by high performance liquid chromatography].
AB  - In order to determine a reliable method for measuring oxalic acid, we carried out
      a procedure using high performance liquid chromatography. This method proved to
      be excellent in the case of tea and beer. In the case of urine, however, it had
      some problem from the aspect of reproducibility, although as far as linearity
      measurement, dilution test and recovery rate were concerned, accurate results
      could be obtained. Nevertheless, this method was thought to be unsuitable for
      routine clinical use, at least at present, for the reasons that it took a long
      time to perform the measurement, and because of the high cost of the column used
      in the procedure. The value of the oxalic acid as determined by this method in 24
      hr urine from 12 healthy male volunteers was in the range of 17-47 mg/day
      (average +/- standard deviation: 25.4 +/- 9.0). To correct for their differences
      of physical constitution, dividing oxalic acid value by body weight rather than
      by urinary creatinine or body surface area was found to give a more precise value
      of the norm. From this calculation, it was thought that the normal range of
      oxalic acid value was 0.6 mg/kg or less.

PMID- 8255038
TI  - [Immunohistochemical study on the expression of perforin in tumor infiltrating
      lymphocytes of renal cell carcinoma].
AB  - Perforin is considered to be one of the important cytolytic factors found in the
      granules of killer cells. In this paper we attempted to demonstrate perforin in
      TIL (tumor infiltrating lymphocytes) of 55 human renal cell cancer cases and the
      perforin was proved by staining immunohistochemically with an anti-PFP monoclonal
      antibody. The result indicated that perforin was observed in 98% of the cases,
      while few positive cell was found in normal renal tissues. TILs were further
      characterized into their subsets including CD4+ T cells, CD8+ T cells, NK cells
      and gamma/delta T cells using antibodies specific to their surface markers. The
      antibodies used are anti-Lew3a, anti-Lew2a, anti-Lew19 and anti-delta chain
      antibody. The former two subsets were predominantly found to be infiltrating in
      the tumor tissue, while the latter two subsets were shown to be lesser than the
      former. For examination of the correlation between the presence of perforin and
      the characteristics of infiltrated lymphocyte subsets, double-staining of the
      cells was performed using anti-perforin and one of anti-surface marker
      antibodies, respectively. The perforin was found to be expressed on the four
      subsets at different extent. A stronger reactivity of the perforin was found in
      the CD4+ T cells and CD8+ T cells than that in the NK cells and the gamma/delta T
      cells. These findings suggest that perforin may play a role of effector functions
      in the immunological defense mechanism against cancer. To define the significance
      of the expression of the perforin not only on the CD8+ T cells but also on the
      CD4+ T cells is required for further study.

PMID- 8255040
TI  - [Experience of laparoscopic pelvic lymphadenectomy in 10 patients].
AB  - From November 1991 through January 1993, we performed laparoscopic
      lymphadenectomy on 10 patients. These patients were aged 54 to 77 years. All
      laparoscopic procedures were performed under general anesthesia. We dissected
      obturator lymph nodes on bilateral side. Total operation time ranged from 127 to
      325 minutes. We could excise 3 to 9 lymph nodes on right side and 0 to 10 lymph
      nodes on left side. Blood loss was 180 ml in one patient, but minimal in the
      remaining 9 patients. Ureteral injury occurred during laparoscopic procedure in
      one patient. This injury could be managed with laparoscopic and cystoscopic
      procedure. Postoperatively complications were observed in 5 procedures, which
      consisted of subcutaneous emphysema in 2 procedures, fever (over 38 degrees C) in
      2, shoulder and arm pain in 1, ileus in 1. The patient with ileus complained of
      abdominal fullness but he was able to ingest. All patients resumed their
      preoperative activity by postoperative day 3 to 5. We believe that this procedure
      was safe and useful for decision making in the management of our patients. We
      need further study on indications and techniques for this procedure.

PMID- 8255041
TI  - [Effects of testosterone on smooth muscle in the isolated rabbit corpus
      cavernosum penis].
AB  - It has been reported that there is no relationship between serum testosterone
      level and erectile function and that testosterone mainly acts on the brain and
      not on the penis. However, we have found that erectile dysfunction in some
      patients with low serum testosterone improved after androgen replacement therapy.
      We therefore studied the effects of testosterone on the contraction and
      relaxation of the corpus cavernosum penis. Four groups of rabbits were studied
      over a similar time span. The testosterone group were non-operated and received
      testosterone propionate 10 mg/day for 14 days before sacrifice. Two groups
      (castration+testosterone group and castration group) were castrated 28 days
      before sacrifice. The castration group received sesame oil for 14 days, and the
      castration+testosterone group received testosterone 10 mg/day for 14 days. Entire
      penis were removed immediately after death by desanguination and dissected to
      obtain corpus cavernosum strips. These strips were suspended under 1 g tension in
      a 20 ml organ bath containing Tyrode's solution. After equilibration for 2 hours,
      the addition of drugs was started. Changes in tension were monitored with an
      isometric transducer and recorded. The vasoactive drugs used were norepinephrine
      bitartrate, 1-phenylephrine hydrochloride, clonidine hydrochloride, acetylcholine
      chloride and vasoactive intestinal polypeptide. The contractility of the corpus
      cavernosum strips increased significantly in the testosterone group and the
      castration + testosterone group, but decreased significantly in the castration
      group as compared with the control after adding norepinephrine, phenylephrine and
      clonidine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255042
TI  - [Some effects of pH, diuretics and organic acids on the uptake of oxalate in a
      renal tubular cell line (LLC-PK1)].
AB  - The effects of changes in extracellular pH and treatments with diuretics or some
      organic acids on the uptake of oxalate were studied in an epithelial cell line of
      renal origin (LLC-PK1 cells). The oxalate uptake into the cells exhibited a
      marked sensitivity to extracellular, pH, in the present results with acidic pH
      stimulating and alkaline pH inhibiting the DIDS sensitive uptakes. The uptake of
      oxalate was clearly inhibited by DIDS, proportionally to the concentrations from
      10 microM to 1 mM. Furosemide, chlorothiazide, probenecid and acetazolamide
      inhibited the oxalate uptake significantly. Probenecid has the most potency on
      the inhibition of the uptake in high concentrations, and acetazolamide needed a
      high concentration for the small effect. However, allopurinol has no effect on
      the uptake as well as dicarboxylates (malate, succinate and phenyl succinate) and
      organic acids (urate and para-amino hippurate). We discussed the mechanisms of
      the inhibition against the oxalate uptake concerning with each drug. It was
      suggested that probenecid may inhibit the oxalate carriers directly, while
      furosemide, chlorothiazide and acetazolamide may inhibit then by the direct
      actions and some secondary effects which are provided by those drugs.

PMID- 8255043
TI  - [Surveillance following orchiectomy for stage I testicular tumor].
AB  - Thirty-one cases with clinical Stage I testicular tumor were treated by
      surveillance policy after orchiectomy alone at Cancer Institute Hospital from
      April in 1985 to October in 1991. Histological types were seminoma in 22 cases
      and nonseminomatous germ cell tumors (NSGCT) in 9. Relapses were observed in 7
      (22.5%) patients between 2.5 and 9.3 months after orchiectomy. Five (22.7%) of 22
      seminoma and 2 (22.4%) of 9 NSGCT recurred and received further cis-platin based
      chemotherapy. In all of 5 seminoma and one of NSGCT cases recurrences developed
      in the retroperitoneal lymph nodes and in another NSGCT case lung metastasis was
      observed. All patients have been treated with success and are alive without
      evidence of disease between 5 and 48 months after salvage therapy. One of the
      recurrent cases with seminoma had an evident retroperitoneal metastasis
      misdiagnosed as the small intestine at staging retrospectively. And 2 of 3
      seminoma cases and one of 2 NSGCT cases with minimally abnormal findings in the
      retroperitoneal lymph nodes had recurred. Surveillance policy may not be adequate
      for patients with these changes. But overall survival rate of stage I testicular
      tumors were estimated 100%. And relapse were observed in a small number of stage
      I without "minimally changes". So we regarded that surveillance policy was valid
      in patients with clinical stage I testicular tumor under careful staging and
      intensive follow up.

PMID- 8255044
TI  - [Development of bladder capacity, nocturnal urinary volume and urinary behavior
      in nonenuretic and enuretic children].
AB  - Bladder capacity, nocturnal urinary volume and nocturnal urinary behavior were
      investigated in 1751 nonenuretic and 282 enuretic children in two primary schools
      and four kindergartens. The results were as follows: 1. A statistically
      significant linear correlation was observed between the age and the bladder
      capacity in the morning and daytime, as well as nocturnal urinary output, in
      nonenuretic children. 2. The bladder capacity of enuretic children was smaller in
      the ages below 6 but larger in the ages over 7 than that of noneuretic children.
      It was not likely from this evidence that an immature bladder capacity was a
      primary cause of enuresis. 3. For the estimation of the maximum bladder capacity
      in the study of enuresis, urinary output in the morning immediately after
      awakening with sufficient urinary sensation was thought to be more reasonable
      than that in the daytime, because output in the morning was approximately 50%
      more than that of the daytime. 4. Ten to 15% of nonenuretic children showed
      nocturnal polyuria with nocturnal urination after complete awakening more than
      one time every week. It was also not likely from this evidence that polyuria was
      a primary cause of enuresis. 5. The overall occurrence rate of enuresis was 14%,
      higher in males up to the ages of 9, and almost equal in males and females after
      the ages of 10. 6. The average age for the spontaneous disappearance of enuresis
      was 7.3 y.o., therefore, adequate treatments for enuresis should be instituted
      after the age of 8.

PMID- 8255045
TI  - [Obliterative arteriopathy in renal transplantation: an immunocytochemical
      analysis].
AB  - Obliterative arteriopathy is one of the major obstacles to long-term survival of
      human renal allografts. However, the cellular composition of obliterative
      arteriopathy has been incompletely characterized. We have performed
      immunocytochemical investigations of cellular components of obliterative
      arteriopathy and also investigated immunophenotypic features of proliferating
      smooth muscle cells in these lesions. Three renal allografts that had been
      removed due to rejection were available for this study. Time lapse between
      transplantation and removal of the renal allograft in these patients was 2
      months, 5 months, and 4 years and 9 months, respectively. Tissue blocks cut from
      these renal allografts were fixed in methanol-Carnoy's fixative, and embedded in
      paraffin. Serial sections from each block were cut and used for histopathological
      and immunocytochemical studies. Monoclonal antibodies used for this study were as
      follows: anti-muscle actin antibody, HHF35; anti-smooth muscle actin antibody,
      CGA7; anti-vimentin antibody; anti-desmin antibody; anti-macrophage antibody,
      HAM56; and anti-Factor VIII-related antigen antibody. In all the allografts,
      obliterative arteriopathy was observed in the interlobular and arcuate arteries.
      In an early stage of proliferative lesions (2 months), the hyperplastic intima
      consisted largely of macrophages, intermixed with smooth muscle cells. At this
      stage, smooth muscle cells at the luminal site stained positive with HHF35, but
      negative with CGA7. In older lesions (5 months, 4 years and 9 months), however,
      the thickened intima consisted almost entirely of smooth muscle cells. At this
      stage, smooth muscle cells stained positive with both HHF35 and CGA7.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8255046
TI  - [Computed tomography in the diagnosis of transitional cell carcinoma of the renal
      pelvis].
AB  - CT scans were carried out on 25 patients with transitional cell carcinoma of the
      renal pelvis. Of the 25 patients, tumors were identified in 24 patients (96%) and
      not in one patient on CT scan. Of the 24 patients the tumor was delineated as a
      solid mass in the renal pelvis and/or calyx in 15 and as an infiltrating mass in
      the renal parenchyma in 8 on CT scan. The depth of invasion was correctly
      estimated by CT in 18 of the 25 patients (72%). Whereas the tunica muscularis of
      the renal pelvis or the renal parenchyma was found involved in 3 of 10 patients
      (30%) in whom the diagnosis was made that the tumor was limited to the renal
      pelvic mucosa, the correct diagnosis was possible in 22 of 25 patients (88%) in
      whom the tumor was confined to the renal pelvic wall (pTa-pT2) or more invasive
      (pT3-pT4). In 6 of 7 patients with lymph nodes matastases enlarged lymph nodes
      were seen on the CT scan. In all 7 cases the primary tumor was classified as a
      pT3 or pT4 invasive disease. Based on the results presented above, it may be
      concluded that CT scan is valuable in making the diagnosis of transitional cell
      carcinoma of the renal pelvis and also in determining whether the tumor has
      invaded beyond the renal pelvic wall, thereby providing guidelines for the
      adequate treatment.

PMID- 8255047
TI  - [Clinical studies of renal pelvic and ureteral tumors: an analysis of 611
      registered cases and progress of treatment].
AB  - A review of 611 cases of renal pelvic or ureter tumor registered in Tokai
      Urological Tumor Registry for the past 10 years from 1980 and comparison of
      results between the first and latter half was made. The number of renal pelvis
      tumor was 347 and that of ureter tumors was 264. Clinical stages and pathological
      grades of the tumor were as follows; Ta, 11.9; T1, 31.8; T2, 14.4; T3, 24.3; T4,
      17.6% and G1, 10.5; G2, 49.3; G3, 33.0%. Higher stages and grades were observed
      in the recent 5 years. Of 409 cases (66.9% in total cases) treated by total
      nephroureterectomy, 28.3% of the first and 49.0% of the latter half were treated
      adjunctively by chemotherapy. Five years relative survival rates of these two
      groups were 49.4 and 47.3%, respectively, suggesting no improved results. A new
      treatment strategy such as neoadjuvant chemotherapy or lymphadenectomy is
      expected to improve the prognosis.

PMID- 8255048
TI  - [Clinical observations of advanced renal cell carcinomas--the chronological
      change between 1975 and 1991].
AB  - An analysis has been undertaken to determine chronological changes that have
      occurred in the clinical features and treatments of advanced renal cell
      carcinomas. To accomplish this, 96 renal cell carcinoma cases, handled by the
      authors' department and at the branch hospital, were divided into two groups: 48
      patients treated between 1975 and 1983 (group 1) and 48 patients treated between
      1984 and 1991 (group 2). Between the two groups, no differences were seen in the
      sex ratio, the mean age, and the ratio of those who were found to be advanced
      cases at the time of diagnosis and those whose cancers had advanced after
      undergoing a nephrectomy. Concerning treatment, interferon (IFN) and UFT were
      more frequently used in treating group 2 than group 1, and chemotherapy,
      radiotherapy, and endocrine therapy less frequently used. No differences were
      seen in the prognosis between the two groups; however, in those who had advanced
      after nephrectomy, group 2 cases survived for a significantly longer period than
      did group 1 cases. Patients who survived for 5 years or longer accounted for two
      cases in group 1 and 5 cases in group 2 and combination therapies involving
      surgery, IFN, UFT, or similar medications were used for their treatments. These
      results suggest that adjuvant therapies, such as surgery, IFN, and UFT, have
      possibly contributed to prolonging survival, especially for cases that advanced
      after nephrectomy.

PMID- 8255049
TI  - [The effects of the treatment for acute rejection with OKT3 monoclonal antibody
      treatment on the long-term results of cadaveric kidney transplantation].
AB  - Although the efficacy of OKT3 monoclonal antibody (OKT3) upon the steroid
      resistant rejection is well known, its beneficial effect on long-term result of
      kidney transplantation has not yet been well examined in Japan. A retrospective
      group study was performed to analyze the effect of OKT3 on the cadaver kidney
      allograft. Between September 1987 and October 1990, a total of 77 patients from
      four different hospitals were classified into 2 groups. Thirty-four patients from
      2 hospitals were entered OKT3 therapy group and 43 patients from the other
      hospitals were entered steroid therapy group. Initial immunosuppression comprised
      low-dose cyclosporine (6 mg/kg), steroid and antilymphocyte globulin in both
      groups. In OKT3 therapy group, acute rejection episodes those were considered
      steroid resistant were observed in 7 patients. They were treated with OKT3
      monoclonal antibody. Of the seven patients, six recovered normal renal function.
      The mild rejection in OKT3 therapy group was treated with high-dose steroid.
      Minimal follow-up was 2 years. The 2-year graft survival was 82.4% in OKT3
      therapy group and 74.4% in steroid therapy group. Although the improvement on the
      2 year graft survival with OKT3 treatment was 8%, the difference between two
      groups was not statistically significant.

PMID- 8255050
TI  - [Intra-arterial CDDP and CDDP plus THP-ADM therapy for bladder cancer].
AB  - From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4
      tumors) with bladder cancer were treated with single injection of CDDP (150-200
      mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4
      tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40
      mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents
      was equally given for the both sides, while 75% dose was given to the tumor side
      to the case with unilateral localized tumors. Then total or partial cystectomy
      was followed. When residual invasive cancer was pathologically present in
      operative specimens, patients underwent three to six courses of adjuvant
      chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial
      chemotherapy in group A and B were 39% and 62%, respectively. Pathological
      response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were
      17% in both group. After total cystectomy, the 2-year cancer specific survival
      rates of 17 patients in group A and 22 patients in group B were 75% and 59%,
      respectively. The 2-year cancer specific survival rates of 8 patients in group A
      and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer
      death occurred thereafter in the patients of group A during another three years.
      The 3-year cancer specific survival rate of 9 patients after partial cystectomy
      (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255051
TI  - [Ultrastructure of immotile spermatozoa obtained from infertile male patients].
AB  - We sometimes experienced infertile patients whose sperms had no motility but were
      not stained by Eosin Y. In this paper we report five cases of so-called "immotile
      spermatozoa". The ultrastructure of sperm tails was examined by transmission
      electrone microscope (TEM). These cases were selected from the out-patient
      population who attended infertility clinic of our department. The semen analyses
      showed that all the cases had sperm motility below 1% and more than 90% of the
      spermatozoa were proven alive. Family history revealed that one case had an
      infertile sibling. None of them had situs inversus, bronchiectasis and chronic
      sinusitis which are classic trias of Kartagener's syndrome. They had no symptoms
      of upper respiratory tract infection which was caused by the abnormality in the
      flagella of the respiratory tract. The TEM pictures of sperm tails showed partial
      deletion of inner dynein arms in two cases, lack of central microtubular doublets
      (so-called 9 + 0) in two cases and disarrangement of microtubular doublets in one
      case. For the treatment of these cases there is no effective means but AID.
      However, the rapid progress of IVF-ET techniques and a report that the
      spermatozoa from Kartagener's syndrome had showed penetration into eggs
      encouraged us to think the micromanipulation of spermatozoa with IVF-ET as a
      hopeful option of the treatment in the near future.

PMID- 8255052
TI  - [An atypical multilocular cystic nephroma presenting recurrent lumbago].
AB  - A 54-year-old female suffered from repeated flank pain. A large, irregular cystic
      mass that compressed and distorted the left pelviocalyceal system was found. She
      underwent left nephrectomy. The cyst arose from the inner zone of the kidney.
      Although monolocular grossly, it was compatible with the multilocular cystic
      nephroma on the microscopic examination.

PMID- 8255054
TI  - Health care reform--quo vadis?

PMID- 8255053
TI  - [A case of epididymal sarcoidosis].
AB  - We reported a case of epididymal sarcoidosis. The patient was a 13-year-old boy
      with a chief complaint of right scrotal mass. On physical examination, a firm,
      nontender 7 mm mass was palpable in the right hemiscrotum and appeared to involve
      the head of the epididymis. Ultrasonography showed a highly echogenic mass in the
      epididymis. A routine chest X-ray revealed lymphadenopathy of the mediastinum and
      reticular shadows in bilateral lung fields. Because the lesion might be confined
      to the epididymis, a partial epididymectomy was performed. The histopathologic
      specimen showed noncaseating granulomas consistent with sarcoidosis. Lung
      biopsies also revealed noncaseating granulomas. Subsequent pulmonary function
      studies revealed a mild obstructing ventiratory defect, therefore therapy was
      instituted with systemic steroids. There were no further recurrent scrotal
      masses. Although sarcoidosis is known to affect many organs, involvement of the
      genital system is relatively rare. Most of the patients with intrascrotal sarcoid
      lesions have an abnormal chest X-ray. We need to differentiate these lesions from
      advanced testicular cancer. This is the 5th case of intrascrotal sarcoidosis in
      Japanese literature.

PMID- 8255055
TI  - Emergency room care and civil liability.

PMID- 8255056
TI  - Kansas women physicians respond to survey.

PMID- 8255057
TI  - The identification of psychiatric problems in primary care medical settings.

PMID- 8255058
TI  - Practical psychopharmacotherapy for the non-psychiatrist.

PMID- 8255059
TI  - Practical office-based counseling skills for the primary care physician.

PMID- 8255060
TI  - Mental health issues in rural settings.

PMID- 8255061
TI  - Tetanus in Kansas, 1993.

PMID- 8255062
TI  - Digoxin is important for treating CHF.

PMID- 8255063
TI  - Concept of simulation surgery.
AB  - The concept of simulation surgery was first proposed by Fujino in 1989 and
      reinforced in 1991. It is divided in two sections; empirical simulation surgery,
      where the surgical procedure is designed first in the surgeon's brain, and
      computer simulation surgery, where the disease condition and the possible
      surgical procedures can be viewed in three-dimensions (3D) either on a computer
      monitor, or by means of a solid 3D model, crafted from computer generated data,
      before proceeding to the actual surgery itself. Each of these sections is
      subdivided into three subsections; morphological, functional and psychological
      simulation surgery, respectively. Along those lines, the concept of simulation
      surgery is discussed, with special reference to plastic and reconstructive
      surgery.

PMID- 8255064
TI  - Notable minimum value of relative risk recognized by Japanese epidemiologists and
      rule of proof in civil trial: questionnaire survey.
AB  - Members of The Japanese Society of Cancer Epidemiology were questioned about
      relative risk in cancer epidemiology. The notable minimum value of relative risk
      recognized by the epidemiologists distributed from 1.1 to 5.0, and the mean and
      the standard deviation of the notable minimum value were 1.92 and 0.760. In civil
      litigation of United States a plaintiff must prove one's case by a "preponderance
      of evidence," which means that a causal relationship between risk factors and a
      health disturbance to a plaintiff is proved when relative risk is 2.0 or more.
      The mean value 1.92 of the notable minimum value of relative risk nearly
      corresponded to the relative risk 2.0, which indicates that opinion of Japanese
      epidemiologists did not disagree with the rule of the proof in civil litigation
      of United States. It is mentioned that the standard of the proof should be "high
      probability" based on "a high level of conviction in the judge's own mind" in
      Japanese civil trials, and that the "high probability" means that relative risk
      is 5.0 or more if we dare to quantify the vagueness. This value corresponded to
      the maximum value of the notable minimum relative risk in the questionnaire to
      the Japanese epidemiologists. In civil litigation of Japan, the standard of the
      proof based on epidemiological results may be more conservative than the opinion
      of Japanese epidemiologists.

PMID- 8255065
TI  - Thymectomy in human renal transplantation.
AB  - We reviewed 17 patients submitted to thymectomy via the suprasternal notch
      (Yoshimatsu Method I), which was performed before transplantation in 12 patients
      and after transplantation in 5 patients. There were no complications of
      thymectomy. Graft survival of our patients with thymectomy was better than that
      for the overall allograft survival in Japan transplant registry for the same
      period. Pathologic studies revealed that involution of the cortex was not
      observed in 5 thymuses removed from recipients who had thymectomy after
      transplantation even though 2 of them had received 6.4 g and 3.5 g of
      prednisolone for 19 months and 32 months, respectively.

PMID- 8255066
TI  - Toxicity of intraperitoneally administrated silicon tetraalkoxides in male ICR
      mice.
AB  - The toxicities of silicon tetraalkoxides, including tetramethoxysilane
      [Si(OCH3)4, TMOS], tetraethoxysilane [Si(OC2H5)4, TEOS], tetrapropoxysilane
      [Si(OC3H7)4, TPOS] and tetrabuthoxysilane [Si(OC4H9)4, TBOS], were investigated
      with intraperitoneal injection of 1,000 mg/kg of each compound. TMOS, as well as
      TEOS, caused acute tubular necrosis. Blood biochemical examination revealed
      elevation of blood urea nitrogen and creatinine in mice treated with TEOS, TPOS
      and TBOS, though TMOS treated mice died and therefore could not be examined. The
      severity of nephrotoxicity differs among these silicon tetraalkoxides. The
      spleens of mice treated with TMOS exhibited cytolysis in the white and red pulp,
      suggesting direct injury to the spleen. The kidney seems to be a common target
      organ of silicon tetraalkoxides.

PMID- 8255067
TI  - Pityrosporum ovale and skin diseases.
AB  - Pityrosporum ovale is a lipophilic yeast belonging to the normal human cutaneous
      flora in adults. It is not only a saprophyte but also an opportunistic pathogen
      associated with: Pityriasis versicolor, Pityrosporum folliculitis, seborrhoeic
      dermatitis and some forms of atopic dermatitis. Even systemic infections have
      been described. In pityriasis versicolor P. ovale change from the blastospore to
      the mycelial form under the influence of predisposing factors such as high
      temperature, high relative humidity or endogenous factors such as greasy skin,
      sweating, heredity, immunosuppressive treatment or disorders. Topical treatment
      is often effective but short term treatment with fluconazole, ketoconazole or
      itraconazole is also effective. The great problem is recurrence and to avoid this
      a prophylactic treatment is mandatory. Pityrosporum folliculitis is a chronic
      disease characterized by pruritic follicular papules and pustules located
      primarily on the upper trunk, neck and upper arms. Under the influence of the
      same predisposing factors as in pityriasis versicolor P. ovale increase in
      numbers in the hair follicles. The main differential diagnosis is acne vulgaris.
      The effect of antifungal treatment is often dramatic. There are now many studies
      indicating that P. ovale plays an important role in seborrhoeic dermatitis. Many
      of these are treatment studies showing a good effect of antimycotics parallelled
      by a reduction in number of P. ovale. Severe seborrhoeic dermatitis often
      difficult to treat is associated with AIDS. In a recent study we have evidence
      for a slight T-cell defect in many patients with seborrhoeic dermatitis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8255068
TI  - Function-related changes in energy metabolism in the nervous system: localization
      and mechanisms.
AB  - Previous neuroanatomical and electrophysiological methods to localize functional
      activity in the nervous system focus on perikarya as the sites of the activity.
      Metabolic mapping of local functional activity in the nervous system provides a
      new dimension, the activity in the neuropil. Studies of local glucose utilization
      have shown that energy metabolism is increased by functional activation, but the
      effects are mainly in the terminal projection zones of the activated pathway.
      Electrical stimulation of a pathway raises glucose utilization in the projection
      zones of the pathway in almost direct proportion to the spike frequency. For
      example, electrical stimulation of the sciatic nerve produces frequency-dependent
      metabolic activation in the dorsal horn of the lumbar cord, where the axonal
      terminals of the afferent pathway reside, but no apparent metabolic effects in
      the cell bodies of the pathway in the dorsal root ganglia. Functional activation
      of the hypothalamo-hypophysial pathway by salt-loading increases glucose
      utilization in the pituitary neural lobe, where the terminal axons of the pathway
      reside, but not in the paraventricular and supraoptic nuclei, the sites of the
      cell bodies of origin of the pathway. Reflex activation by hypotension of
      pathways to these nuclei from brain stem structures involved in baroreceptor
      reflexes, however, increases glucose utilization in these nuclei. Depolarization
      induced by electrical stimulation, extracellular K+, or opening of Na+ channels
      with veratridine, stimulates glucose utilization in neural tissues, and this
      increase is blocked by ouabain, a specific inhibitor of Na+, K(+)-ATPase.
      Activation of this enzyme to restore ionic gradients across cellular membranes
      appears to trigger the functional activation of energy metabolism.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8255069
TI  - [Clinical features of intestinal tuberculosis].
AB  - We had tuberculosis infection cases of gastrointestinal tract diagnosed
      histopathologically during January 1980 to December 1991 in Tokyo National Chest
      Hospital. There were 12 cases (male 8, female 4) from 24 y.o. to 88 y.o. (mean 50
      y.o.). We got histopathological specimen by operation (6 cases), biopsy (4), and
      section (2). Pulmonary tuberculosis was complicated in 8 cases, 7 cases had
      cavity formation and another case was miliary tuberculosis. Distribution of
      tuberculous lesion was colon (7 cases), small intestines (5), cecum (2), rectum
      (1) and esophagus (1). First symptom was mainly abdominal symptom such as
      abdominal pain and diarrhea. There were a perforative peritonitis and a
      intestinal obstruction during chemotherapy. Three died cases complicated low
      albuminemia. We suppose that serum albumin is one of the useful marker of
      patient's prognosis.

PMID- 8255070
TI  - [Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, administered at the
      different periods of infection in Mycobacterium intracellulare--infected mice].
AB  - Therapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648,
      administered at the different periods of infection in Mycobacterium
      intracellulare-infected mice was studied. Mice were infected intravenously with
      M. intracellulare (9.8 x 10(6) CFU/mouse) and then were given 0.4 mg of KRM-1648
      emulsified in 2.5% gum arabic-0.2% Tween 80 by gavage, once daily six times per
      week, from day 1 to week 4, week 2 to week 6, week 4 to week 8, and week 8 to the
      end of experiment (week 12). Judgement of the therapeutic efficacy of the drug
      against the infection was done on the basis of incidence and degree of gross lung
      lesions, % organ weight (organ weight/body weight x 100), and bacterial loads in
      the lungs and spleen. The lung lesions were not observed in the control and KRM
      treated mice at 4 weeks after infection (KRM treatment: day 1 to week 4). At 6
      weeks after infection (KRM treatment: week 2 to week 6), the lung lesions were
      observed in all control mice, whereas 3 of the 5 mice given KRM-1648 did not show
      the lesions. At 8 weeks after infection (KRM treatment: week 4 to week 8), the
      lung lesions were observed in all control and KRM-1648-treated mice, but the
      degree of the lung lesions was much more slight in mice given KRM-1648 than in
      control mice. The incidence and the degree of the lung lesions at 12 weeks after
      infection (KRM treatment: week 8 to week 12) was not different in both
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255072
TI  - [Studies on 13 cases of active tuberculosis diagnosed at autopsy for the first
      time].
AB  - It is reported not only that the incidence of active tuberculosis has not
      decreased but also that the cases of active tuberculosis who had been diagnosed
      at autopsy for the first time may have increased. The background factors and
      clinical courses of 13 cases of active tuberculosis whom we could not diagnose as
      tuberculosis until autopsy were investigated. According to the autopsy reports,
      the three fourths of the cases had active tuberculosis lesions in several organs
      as miliary tuberculosis. All of the cases were treated in serious condition of
      liver cirrhosis, leukemia, and other malignant diseases. Although fever of
      unknown origin was an important symptom, it was difficult to make a correct
      diagnosis because the fever was thought to be originated not from active
      tuberculosis but from the underlying diseases themselves. It was also difficult
      to diagnose from chest x-ray findings unless tuberculosis was suspected
      clinically. The education about tuberculosis should be held repeatedly. And we
      should try to think from different direction for the strange and unexpected
      clinical features of the patients with liver cirrhosis, leukemia, and other
      malignant diseases.

PMID- 8255071
TI  - [A tuberculosis epidemic in one kindergarten].
AB  - In a routine PPD skin test among 1st grade pupils in 4 elementary schools,
      Fukushima prefecture in April 1989, the number of pupils that showed strongly
      positive was unusually high. Moreover, 2 tuberculosis cases were detected among
      them. Since those children graduated the same kindergarten, and one of 6
      kindergarten teachers had been complaining cough and hoarseness for about 3 to 5
      months before being diagnosed as a smear positive patient in the contact survey,
      she was suspected to be the source of infection. Meanwhile, she had been treated
      for common cold and chronic bronchitis in several clinics, therefore, the main
      cause of this epidemic was due to the doctor's delay in detecting the case. With
      the discovery of 2 additional cases in the contact survey of the kindergarten,
      there were 5 cases altogether including the index cases. Three of 4 children's
      cases had been vaccinated with BCG. If the children who showed strong reaction to
      tuberculin and eventually treated prophylactically with isoniazid were assumed
      the infected, the rate of development of disease among the infected was 13.6 to
      27.3%. Usually, lymph node enlargement of the hilum is said not to be observed
      among vaccinated, though slightly, it was evident among the cases in this
      epidemic.

PMID- 8255073
TI  - [Pulmonary disease due to Mycobacterium xenopi].
AB  - A 54-year old man with pulmonary disease due to Mycobacterium xenopi is
      described. He had a history of pulmonary tuberculosis at 8 years of age. He was
      admitted to our hospital in October 1992, complaining of productive cough and
      fever. A chest X-ray on October 20 showed an infiltrative shadow with a cavity,
      although chest X-ray picture on October 2 showed only inactive shadow, in the
      right upper lobe. Acid-fast organisms were seen in his sputum specimens and M.
      xenopi was identified by culture. The isolates were confirmed to be M. xenopi by
      the DNA-DNA hybridization method. He was treated with isoniazid, rifampicin and
      streptomycin. The fever decreased within a week. After two months of therapy,
      sputum cultures became negative and chest X-ray findings improved. It was
      concluded that this is a case of rapidly progressed pulmonary disease caused by
      M. xenopi in the normal host. This patient's condition responded to
      antituberculosis drugs.

PMID- 8255074
TI  - [The decision making process in tuberculosis control programme].
AB  - The main purpose of this paper is to demonstrate relevance of the medical
      technology assessment (MTA) approach in the decision making process in the
      tuberculosis control programme. Recently MTA has progressed remarkably under the
      pressure of limited medical resources and necessity for rational utilization of
      those resources. This approach has also been assisted by the development in
      related technologies, such as statistics and the managerial sciences. The author
      demonstrates the feasibility of the MTA approach in tuberculosis control
      programmes, with special emphasis on the applicability of the mathematical model
      in risk-effectiveness analysis, citing several examples from his recent works. A
      critical analysis of the screening chest radiophotography (Mass Miniature
      Radiophotography, MMR) is a good sample of risk-effectiveness analysis, where
      benefit from early detection of tuberculosis is quantified and compared with the
      possible risk due to radiation exposure. A mathematical model is used to simulate
      the fate of tuberculosis patients with or without treatment. The benefit is
      computed in terms of lives saved, life-years extended, and treatment costs saved
      with or without the MMR programme. In Japan, it is concluded that MMR cannot be
      rationalized as a life-saving intervention in young age-groups, nor being
      economically cost-effective for wider age ranges. Based on the estimated trend of
      risk of infection of Japan now and in the near future, the infection status of a
      cohort born around 1990 can be calculated. Applying risk of clinical breakdown of
      tuberculosis to the above infection status and the assumed level of protective
      efficacy of BCG vaccination, assessment of the BCG vaccination programme can be
      made, under various hypothetical modes of vaccination, whether vaccinated to the
      newborn or to school entrants, whether revaccinated or not, and when, etc. The
      analysis revealed that the revaccination has very limited effectiveness, which in
      turn emphasizes the importance of the primary vaccination with optimum technical
      level. Under the very low prevalence conditions of tuberculous infection as in
      Japan of present (annual risk of infection estimated at ca. 0.05%), the
      determination of a cut-off point for selecting those eligible for
      chemoprophylaxis with isoniazid is a good example of a clinical decision problem
      which has a narrow spectrum of positive risk benefit ratio. Using the ROC
      analysis of the tuberculin testing, risk of excessive tuberculosis deaths and
      that of fatal hepatitis cases are compared under varying cut-offs, which leads to
      a conclusion that for the presumably very low-risk population chemoprophylaxis
      should be given to those with 20mm diameter or more of erythema.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8255075
TI  - Analysis of enzyme-linked immunosorbent assay data for antigen quantitation using
      Lotus 1-2-3 software on a personal computer.
AB  - Absorbance data obtained in double-antibody sandwich enzyme-linked immunosorbent
      assay tests for quantitation of antigens are analyzed by a personal computer
      using the Lotus 1-2-3 software package. The sigmoid standard curve is processed
      by an iterative weighted regression analysis in the logit-log domain to obtain a
      linear dose-response relationship. A macro program is developed for quick
      calculation with easy operation, which is suited for routine laboratory tests in
      biomedical fields.

PMID- 8255077
TI  - Pathological findings in dicephalus dipus dibrachius: implications for mechanisms
      in two pairs of lateral conjoined twins.
AB  - The anatomical and pathological features of two pairs of dicephalic conjoined
      twins (case 1 and 2) are described. Both twins showed duplicitas lateralis
      representing diprosopus dipus dibrachius. There were two complete heads on two
      necks, one thorax, one abdomen and externally normal two arms and two legs. Case
      1 showed dicephalus with anencephaly, two vertebral columns and two spinal cords,
      which converged from the thoracic region distally. The esophagus, stomachs and
      partial small intestines were duplicated, which fused at yolk sac (with Meckel's
      diverticulum). The heart was incompletely fused. The lungs and trachea were
      doubled. Two spinal cords were fused from the thoracic region caudally and showed
      myelomeningocele and Arnold-Chiari malformation in case 2. Two larynxes and two
      thracheas connected with the incompletely fused three lobes of lungs. The
      conjoined lungs were hypoplastic. The heart was single, showing ventral septal
      defect, transposition of great arteries, two cuspid aortic valves and preductal
      aortic coarctation. The duplicated esophagi were conjoined in Y-shape and single
      stomach, duodenum, intestine and colon were found. There were pairs of kidneys,
      adrenal glands and ureters and single female genitalia in both cases. These
      findings indicate that the craniocaudal paleoaxes were separated in the cranial
      region and converted or fused under the thoracic region like a Y-shape. Further
      development defects and deformations might be important factors to form
      malformations in these case.

PMID- 8255076
TI  - Evaluation of various mechanical heart values in the mitral and aortic positions.
AB  - To evaluate the function of various types of mechanical heart valves (Bjork
      Shiley = BS, Medtronic Hall = MH, St. Jude Medical = SJM, Duromedics = DM),
      hemodynamic studies were performed in 236 patients with valve replacement in
      addition to the evaluation of the clinical results. In 144 patients with mitral
      valve replacement including patients with double valve replacement, the degree of
      the postoperative improvements of clinical symptoms and hemodynamics were similar
      in patients with BS, DM and MH valves. There was a tendency for the effective
      orifice area calculated from pressure-half time obtained by continuous-wave
      Doppler (CWD) echocardiography to be larger in MH or DM valves than in BS valve
      of the same size on the average. In 115 patients with aortic valve replacement
      including patients with double valve replacement, there was no significant
      difference in the degree of postoperative reduction of the left ventricular
      hypertrophy among the patients with BS, MH and SJM valves. The mean value of the
      pressure gradient (PG) across the valve at rest obtained by CWD was less than 20
      mmHg in each type of valve without significant difference among the valves. PG
      well correlated with cardiac output (CO) in each type and size of valve, and the
      rate of increase in PG with the increase in CO was smaller in the larger-sized
      valve of the same type and also smaller in MH valve than in BS valve of the same
      size. The frequency of valve-related complications was extremely low in each type
      of valve except for a higher incidence of occult hemolysis in SJM and DM valves.
      Overall, there were no significant differences in the clinical results among the
      patients with valvular prostheses examined. However, MH valve had advantages in
      hemodynamics and a lower incidence of hemolysis.

PMID- 8255078
TI  - c-myc oncogene expression: a marker for females at risk of breast carcinoma.
AB  - In an attempt to identify patients at risk of breast cancer, 9E 10 c-myc
      monoclonal antibody was used to detect the oncogene products in 64 breast tissue
      biopsies. There were 44 specimens of benign breast disorders: 21 from patients
      who developed subsequent breast cancer, and 23 from patients who did not. The
      remainder were malignant tumor biopsies from those who developed breast cancer. C
      myc over-expression was identified in 12 (60%) of the breast carcinomas; it was
      also noted in 13 (62%) of the benign biopsies from patients who developed
      subsequent breast carcinoma. Expression was observed in only 3 (13%) controls-
      patients who did not develop cancer. A prospective study is now warranted to
      determine the clinical usefulness of our findings.

PMID- 8255079
TI  - Growth inhibition of human gastrointestinal cancer xenograft lines by treatment
      with CPT-11 and VP-16.
AB  - A water-soluble and stable camptothecin derivative, CPT-11, was found to possess
      a strong antitumor activity against various murine tumors. In the present study,
      CPT-11 was tested against ten human gastrointestinal cancer xenograft lines
      carried by nude mice. CPT-11 was very effective against nine xenograft lines,
      with the exception of one xenograft. On the other hand, VP-16 was ineffective
      against all these xenograft lines. Therefore, CPT-11 is expected to be clinically
      more effective against gastrointestinal cancer than the topo II targeting agent.

PMID- 8255080
TI  - Thyroid nodules in female uremic patients on maintenance hemodialysis.
AB  - We investigated the incidence of thyroid nodules in female uremic patients on
      maintenance hemodialysis using a high-frequency sonographic scanner. In 47
      (21.0%) of the 224 female normal controls and 33 (55.0%) of the 60 female
      patients, thyroid nodules were detected. The difference in these incidences
      between controls and patients was significant. There were no differences in age,
      duration of hemodialysis, the level of blood urea nitrogen, parathyroid hormone
      or thyroid stimulating hormone between the patients with thyroid nodules and
      those without nodules. Although there is a correlation between uremia and the
      development of thyroid nodules, the details of the underlying mechanism of their
      association remain unclear.

PMID- 8255081
TI  - Tracheal tear during laryngopharyngectomy with gastric transposition.
AB  - Tracheal rupture occurred in 7 of 174 (4%) patients undergoing
      laryngopharyngectomy with gastric transposition. Tracheal tears were classified
      as proximal if they involved the upper two-thirds of the trachea (five patients),
      or distal if they extended into the lower one-third of the trachea (two patients)
      and their clinical features and management analyzed. Predisposing factors,
      including prior radiotherapy (three patients) and preoperative tracheostomy (1
      patient) did not influence the site or severity of tracheal injury. Proximal
      tears were detected incidentally in four patients, but in one patient, manifested
      postoperatively with subcutaneous emphysema and pneumothorax. Distal tears
      manifested dramatically with a ventilatory leak. Adequate access for repair of
      distal tears may necessitate a right thoracotomy while proximal tears may be
      sutured through the cervical incision. Gastric transposition alone did not
      prevent air leak in two patients. Postoperative complications included prolapse
      of the stomach and bilateral pneumothoraces in one patient. Close interaction
      between the surgeon and the anesthesiologist ensured a successful outcome in six
      patients. There was one mortality.

PMID- 8255082
TI  - Prediction of outcome in "resectable" esophageal carcinoma.
AB  - A retrospective review was performed of 51 patients with esophageal carcinoma,
      deemed "resectable" by preoperative workup (e.g., CT scan, barium swallow), who
      presented to Hahnemann University Hospital between 1980 and 1991. This
      represented 21.8% of the total number of patients (234) with esophageal cancer
      who presented during that time period. At exploration, only 21 of the 51 patients
      (41%, or 9% overall) were truly resectable; 59% had more extensive disease than
      was appreciated preoperatively and that precluded resection for cure. Of the 21
      patients resected for cure, 24% were alive at two years and only 5% were alive at
      3 years. Neither age, gender, tumor type nor location in the esophagus
      significantly affected overall survival. Furthermore, none of these parameters,
      taken as independent variables, were able to predict true resectability at the
      time of operation. We conclude that preoperative assessment of resectability,
      even in those patients who appear to be good candidates for cure, remains
      imprecise at best. Given an operative mortality rate of 6-8% (in most series) and
      an overall 3- to 5-year survival rate of less than 10% (even in patients thought
      to have had curative resections), we reinforce the fact that meticulous patient
      selection and multimodality management strategies remain the keys to making any
      impact on this disease.

PMID- 8255083
TI  - Lumbosacral chordoma resection: image integration and surgical planning.
AB  - Clinical, radiographic, and functional outcome parameters were analyzed before
      and after treatment of eight individuals with lumbosacral chordomas studied over
      a 3-year period. Emphasis was placed upon correlation of multiplane images and
      the pathoanatomy of the gross specimen. Surgical resections achieving wide
      margins can be curative. Magnetic resonance imaging of lumbosacral chordomas has
      revolutionized the preoperative anatomic localization of these tumors. Therefore,
      it is critical that the operating surgeon scrutinize the three-dimensional
      location of the tumor and its spatial relationship to surrounding structures
      prior to surgical eradication. A systematic approach for the radiographic
      analysis of tumor extent in lumbosacral chordomas is presented. Four strategic
      areas of preoperative analysis are identified for sacral chordomas and two for
      lumbar neoplasms. Functional outcome after resection is predicted by Stener's
      work. Contamination-free surgery is facilitated by accurate preoperative
      radiographic interpretation of the pathoanatomy by the surgeon.

PMID- 8255084
TI  - Predictors of survival following surgical resection of thymoma.
AB  - The aim of this study was to determine the predictors of long-term survival
      following surgical resection of thymoma. Forty-one patients with a histologically
      proven diagnosis of thymoma were evaluated and treated over a 30-year period
      (1961 to 1991) at our institution. Seven patients (Masaoka stage III or IV) were
      unresectable and were treated by radiotherapy and/or chemotherapy, with an
      overall 5 year survival of 50%. Thirty-four patients underwent primary surgical
      excision of the thymoma, most often through a median sternotomy, with 5- and 10
      year survivals of 90%. Complete excision of the thymoma was achieved in 31
      patients with a median survival of 54 months vs. 17 months if incomplete.
      Independent prognostic factors influencing survival were stage, histology, and
      patients judged to have a benign thymoma at surgery. Although the thymoma was
      associated with myasthenia gravis (8 patients) and second primary cancers (8
      patients), neither factor was associated with overall survival. We conclude that
      the most significant predictors of long-term survival of thymoma include complete
      excision, Masaoka stage I disease, and lymphocytic histology. Multivariate
      analysis suggested that postoperative chemoradiotherapy may impact on survival.

PMID- 8255085
TI  - Squamous cell carcinoma of the tongue: experience with 86 consecutive cases.
AB  - Charts from 86 patients treated for carcinoma of the tongue were reviewed to
      identify strategies that might improve patient outcome. Seventy-one patients
      (83%) were black and 69 patients (80%) were male. Overall 2- and 5-year survival
      rates were 20% and 12%, with stage-specific 2-year survivals of 71% (I and II, n
      = 7), 33% (III, n = 15), and 11% (IV, n = 64) (P < 0.01). Patients with well
      differentiated tumors (n = 27) had a higher 2-year survival than that of the
      others (n = 53, 30% vs. 11%, P = 0.05). Six were unclassified. Twenty-three (27%)
      patients underwent primary surgical resection and lymphadenectomy with or without
      adjuvant therapy. Two-year overall and disease-free survivals were 43% and 26%,
      respectively. Fifty (58%) patients received radiotherapy with or without
      chemotherapy, achieving 2-year overall and disease-free survivals of 12% and 6%
      (P < 0.01). The remaining 13 patients received chemotherapy alone or no treatment
      and survived an average of 6 months. Distant metastasis were diagnosed in 14
      patients (16%). Tongue carcinoma in this socioeconomic setting was characterized
      by late diagnosis and poor prognosis. Degree of tumor differentiation, disease
      stage, and treatment modality seemed to correlate with prognosis. Surgery, when
      possible, achieved superior results for disease control and survival. While
      cancer prevention efforts are critical, steps to identify high-risk groups to
      implement early detection programs may help improve outcome for these patients.

PMID- 8255086
TI  - Response with combined modality treatment in childhood rhabdomyosarcoma.
AB  - Children diagnosed with rhabdomyosarcoma at the Tata Memorial Hospital during the
      period January 1986-December 1988 were studied. All were treated with combination
      chemotherapy incorporating vincristine, Adriamycin, and cyclophosphamide given
      sequentially in repeated cycles over 18 months, along with local radiotherapy. Of
      24 patients, 18 patients had advanced-stage disease at onset. All patients have
      been followed up for 18 months or more. Of the 11 patients with group III
      disease, six are in complete remission; of the six patients with group IV
      disease, two patients are in complete remission. These results are clearly better
      than those achieved in the past, where surgery was employed as the primary
      modality of therapy with chemoradiotherapy given only for patients with group IV
      disease.

PMID- 8255087
TI  - The size of regional lymph nodes does not correlate with the presence or absence
      of metastasis in lymph nodes in rectal cancer.
AB  - We evaluated the relationship between the size of regional lymph nodes and the
      presence of metastasis in them in rectal cancer. Of 1,064 lymph nodes in 46
      specimens, 133 (13%) were found to have metastases. A half of the positive nodes
      and most of the negative ones were less than 5 mm in diameter. Therefore, we must
      find lymph nodes smaller than 5 mm in diameter for assessment of lymph node
      metastasis. Although positive nodes were larger than negative ones, there was no
      significant difference. However, when comparing the size of lymph nodes in
      relation to their location, the epi- and pararectal lymph nodes larger than 10 mm
      in diameter were highly suggestive of metastases, but the size of the lymph node
      was not a reliable indicator of lymph node metastases in other situations.

PMID- 8255088
TI  - Psychologic and cosmetic self-assessments of breast conserving therapy compared
      with mastectomy and immediate breast reconstruction.
AB  - Cosmetic and psychologic morbidity was evaluated by patients' self-assessment in
      42 patients who underwent breast conserving therapy (BCT) and 48 patients who
      underwent mastectomy with immediate breast reconstruction (MIBR). Although sexual
      adjustment and fear of cancer recurrence were not significantly different between
      the two groups, body image was rated as significantly better in the BCT group.
      Additionally, in the MIBR group, nine patients expressed concern about abdominal
      or back scars and 15 related abdominal or back pain. Eighty-three percent of the
      BCT group indicated BCT as a future choice of treatment, whereas only 38% of the
      MIBR group indicated MIBR as a future choice of treatment. Therefore, body image
      and patients' satisfaction were thought to have been improved by BCT, but
      psychologic morbidity was the same in both groups.

PMID- 8255089
TI  - Secretion of vasointestinal peptide by a primary liver tumor with rhabdoid
      features.
AB  - A 5-year-old child presented with an unresectable liver neoplasm, the histology
      of which resembled a malignant rhabdoid tumor. Clinical course was unrelenting
      despite therapy, and the child died four months later. During the course of her
      illness, she developed watery diarrhea and was found to have a high serum level
      of vasointestinal peptide (VIP). This is the first report of a childhood tumor
      with rhabdoid features to secrete VIP.

PMID- 8255090
TI  - Vulvar carcinoma with 0.5 mm of invasion and associated inguinal lymph node
      metastasis.
AB  - A case of vulvar carcinoma with 0.5 mm of invasion treated by radical wide local
      excision only, which later developed ipsilateral inguinal lymph node recurrence,
      is presented. This represents the least amount of invasion reported resulting in
      inguinal lymph node metastasis. Review of the literature of stage I vulvar
      carcinoma with less than 1 mm of invasion indicates that this phenomenon occurs
      in only 1.6% of all patients who have undergone inguinal lymphadenectomy.
      Although this represents the second report of ipsilateral inguinal nodal
      metastasis associated with less than 1 mm of invasion, we continue to perform
      radical wide local excision without ipsilateral inguinal lymphadenectomy until
      more cases demonstrate a higher incidence of lymph node involvement.

PMID- 8255091
TI  - Phase I study of a continuous infusion of high-dose ara-C in conjunction with a
      fixed dose of 2'-deoxycytidine (IND 28108) in patients with refractory leukemia:
      an interim report.
AB  - A total of 16 patients with refractory leukemia have been entered on a phase I
      study employing escalating doses of a 96 h continuous infusion of high-dose
      cytosine arabinoside (ara-C) administered in conjunction with a 120 h infusion of
      a fixed dose (22 g/m2 per day) of 2'-deoxycytidine (IND 28108) as a host
      protective agent. Extramedullary toxicities, even at the highest ara-C dose level
      (e.g. 14 g/m2 per day) were mild (e.g. CALGB grade I or II), and consisted of
      diarrhea, fluid retention, somnolence, hepatic dysfunction, and febrile episodes.
      Neutropenia and thrombocytopenia were noted in all patients, but no serious
      infections or bleeding episodes were encountered. Steady state plasma ara-C
      concentrations of 20-60 microM were observed in patients treated at the 14 g/m2
      dose, and were associated with plasma ara-U concentrations approaching 1 mM.
      Although no complete remissions were obtained at the ara-C dose levels tested to
      date, three partial remissions were noted, and the large majority of patients
      experienced a clearing of peripheral blood blasts. In addition, several patients
      who failed to achieve objective responses exhibited atypically benign clinical
      courses following completion of therapy. These findings demonstrate that 2'
      deoxycytidine protects humans from otherwise lethal doses of high-dose ara-C
      administered by continuous infusion, and substantially ameliorates the
      hematologic and non-hematologic toxicity of such regimens without completely
      abrogating antileukemic activity. Determination of the ultimate efficacy of this
      strategy will require identification of an ara-C maximum tolerated dose and
      evaluation of the antileukemic potential of this regimen in prospective phase 11
      trials.

PMID- 8255092
TI  - Transcription and protein expression of mb-1 and B29 genes in human hematopoietic
      malignancies and cell lines.
AB  - The transmembrane forms of all immunoglobulin (Ig) classes are associated with
      two glycoproteins, mb-1 and B29, that are crucial for signal transduction
      following antigen binding to the Ig molecule. We have investigated the
      transcription and protein expression of mb-1 and B29 genes during B-cell
      development. Sixty human continuous cell lines (35 B-lineage, 11 T-lineage, 11
      myeloid-lineage and three non-hematopoietic) and 75 hematopoietic malignancies
      (55 B-lineage, 12 T-lineage and eight myeloid-lineage), were tested for RNA
      expression by Northern blotting experiments with the mb-1 pRA3 cDNA probe, and a
      newly isolated B29 cDNA probe. Protein expression was analyzed by
      immunofluorescence microscopy of cytocentrifuge preparations, which were labeled
      with the anti-mb-1 HM57 monoclonal antibody (mAb) and an anti-B29 polyclonal
      antiserum, directed against intracellular epitopes of these polypeptides. Except
      for two early precursor B-cell lines, mb-1 and B29 transcripts and proteins were
      detected in all B-cell lines and B-cell malignancies, i.e. from immature to more
      mature B cells, irrespective of their Ig class expression. Transcription of mb-1
      genes seems to be down-regulated at the plasma cell stage, because no mb-1
      transcripts and mb-1 proteins could be detected in the four plasma cell lines and
      two plasma cell leukemias tested. B29 transcripts were detectable in these cell
      samples, but low levels of B29 proteins were only detected in one plasma cell
      line. The HM57 mAb gave strong labeling on fresh cytocentrifuge preparations of
      all B-cell samples, and this mb-1 protein expression appeared to be B-cell
      specific. We therefore conclude that the HM57 mAb is well suited for the
      detection of the mb-1 molecule as a pan-B-cell marker for the diagnosis of
      immature and mature B-cell malignancies. The expression pattern of the mb-1
      protein is comparable to that of the CD19 and CD22 antigens, but has the
      advantage of being B-lineage specific. Although B29 protein expression was
      restricted to B-lineage cells, the anti-B29 antiserum is less suitable for
      diagnosis of B-cell malignancies, because of the variable and generally weak
      signals on cytocentrifuge preparations.

PMID- 8255093
TI  - N-RAS gene activation in acute myeloid leukemia: association with expression of
      interleukin-6.
AB  - The 21 kDa proteins encoded by RAS genes are thought to be involved in
      intracellular signal transduction. Expression of RAS genes activated by point
      mutations after transfection into mammalian cells can modulate the response of
      these cells to exogenously added growth factors and their expression patterns of
      growth factors. We analyzed leukemic cells from 50 patients with acute myeloid
      leukemia (AML) for the presence of activating point mutations of the N-RAS gene
      using polymerase chain reaction (PCR) and differential oligonucleotide
      hybridization. This assay allows semiquantitative determination of the relative
      abundance of cells carrying N-RAS mutations. Clonal activation of N-RAS, noted in
      the large majority of leukemic cells of the six of these patients, was correlated
      significantly (p = 0.0003) with the ability of these cells to express interleukin
      6 (IL-6), previously shown to be expressed at high levels in approximately 30% of
      primary AML cells. In 16 patients, the presence of N-RAS mutations was observed
      only in subpopulations of leukemic cells. The 'subclonal' involvement of some but
      not all leukemic cells was further demonstrated by PCR analysis of individual
      clones grown in soft agar culture. We investigated whether additional,
      complementary changes in oncogene structure occurred in cells exhibiting clonal
      activation of N-RAS. For instance, concomitant activation of N-RAS and
      amplification or rearrangement of c-MYC have been observed in various tumor
      tissues. Southern blot analysis did not, however, reveal gross alternations of
      MYC gene structure or copy number in these cells.

PMID- 8255094
TI  - Acute myeloid leukemia (AML) can be oligoclonal.
AB  - Acute myeloid leukemia (AML) is usually thought to represent a monoclonal
      disease. Among 45 cases of newly diagnosed AML we found rearranged bands in 14
      cases using the Southern blot methodology and immunoglobulin (Ig) joining region
      (JH) or T-cell receptor (TCR beta) probes. In three patients, the findings
      indicated an oligoclonal disease. One case was characterized by several bands in
      the JH blot, some of which reappeared at different time points during remission.
      A second case had monoclonally rearranged Ig-JH sequences in the bone marrow but
      exclusively germline configuration in DNA from peripheral blood cells despite the
      presence of 84% blasts. A third case was characterized by two different, Ig-JH
      and c mu gene rearranged cell populations at diagnosis but relapsed with a
      germline pattern without reappearance of the previous clones. These data indicate
      that AML may differentiate along different lineages with predominant appearance
      of one or the other subclone in the course of the disease.

PMID- 8255095
TI  - Translocation t(3;22)(q27;q11) in non-Hodgkin's malignant lymphoma: chromosome
      painting and molecular studies.
AB  - Translocation t(3;22)(q27;q11) has recently been recognized as a recurrent
      abnormality in non-Hodgkin's malignant lymphoma (NHL). A new gene, LAZ3, has been
      shown to be involved in NHL with 3q27 rearrangement. Two patients with B-cell NHL
      were studied by chromosome painting and Southern blot analysis. Fluorescence in
      situ hybridization to metaphase chromosomes was shown to be an easy way to detect
      the chromosomal abnormality even in metaphase cells with poorly defined
      chromosomes. The gene LAZ3 was rearranged in one patient in the 'major
      translocation cluster region'. The comigration of rearranged LAZ3 and of IGL
      bands suggests that the translocation resulted in the juxtaposition of the two
      genes. This juxtaposition makes possible a potential deregulation of the LAZ3
      gene expression, as previously shown for the MYC and BCL2 genes in Burkitt and
      follicular lymphoma translocations.

PMID- 8255096
TI  - Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic
      characteristics of 115 consecutive cases and risk in seven cohorts of patients
      treated intensively for malignant diseases in the Copenhagen series.
AB  - Therapy-related acute myeloid leukemia (t-AML), often presenting as
      myelodysplasia (t-MDS), has become the most serious long-term complication of
      cancer therapy and offers a unique opportunity to study chemical leukemogenesis.
      Seven cohorts of patients treated for six different types of primary tumor have
      been followed closely for leukemic complications, and 115 consecutive patients
      with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated
      cytogenetically at our institutions during the past 16 years. In patients
      primarily treated with alkylating agents, the risk of t-MDS and t-AML increased
      by approximately 1% per year from 2 to at least 8 years after start of treatment.
      In most cases, the disease presented as t-MDS with loss of a whole chromosome 5
      or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes
      M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II,
      such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with
      drugs reacting directly with DNA, such as cisplatin or alkylating agents, the
      risk of leukemia increased much more steeply from only one year after start of
      therapy. These early onset cases often presented as overt leukemia of FAB
      subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and
      21q22, whereas later onset cases often shared characteristics with cases observed
      after therapy with alkylating agents alone. Both alkylation of DNA and poisoning
      of DNA-topoisomerase II may result in development of t-AML with different
      clinical and cytogenetic characteristics. There may be a synergistic leukemogenic
      effect between the two types of drug, and in patients with germ cell tumors
      treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk
      of leukemia to increase exponentially with increasing doses of cisplatin and
      etoposide.

PMID- 8255097
TI  - Whole arm translocation t(17;18): a non-random abnormality of myeloid cell
      proliferation.
AB  - Whole arm translocation t(17;18) was detected in two patients, one with acute
      monocytic leukemia and the other with acute transformation of chronic myelocytic
      leukemia. Dual-color fluorescence in situ hybridization (FISH) to interphase
      nuclei with alphoid probes specific to chromosomes 17 and 18 showed the presence
      of two very close spots. This feature was interpreted as the conservation of the
      pericentromeric region of the two chromosomes involved in the translocation. The
      present cases add to eight previously reported other patients with whole arm
      translocation t(17;18) (one with FISH studies). Since these patients had either
      myeloid leukemia or myelodysplastic syndrome, it is suggested that the
      t(17;18)(p10;q10) translocation is a new non-random abnormality associated with
      myeloid cell proliferations.

PMID- 8255098
TI  - Use of stroma-supported cultures of leukemic cells to assess antileukemic drugs.
      I. Cytotoxicity of interferon alpha in acute lymphoblastic leukemia.
AB  - Leukemic cells from most cases of acute lymphoblastic leukemia (ALL) rapidly die
      by apoptosis in vitro, unless they are cultured onto bone marrow-derived stromal
      layers. We have recently established a stroma-supported tissue culture technique
      that allows long-term culture of leukemic lymphoblasts. In this study, we used
      this technique to examine interferon alpha (IFN alpha) cytotoxicity to ALL
      blasts. In 16 ALL cases tested (14 B-lineage ALL, 2 T-ALL), the number of cells
      recovered after 7 days of culture on stromal feeder layers was 60-178% (median,
      108%) of those originally seeded. The percentage of lymphoblasts killed by 2000
      U/ml IFN alpha 2b after 7 days of culture, ranged from < 1% to 91% (median, 56%).
      Cytotoxicity was (i) dose-dependent, (ii) eliminated by a neutralizing antibody
      to IFN alpha, and (iii) accompanied by tyrosine phosphorylation of a 135 kDa
      protein, which was detectable after 5 minutes of treatment. Numbers of residual
      normal lymphoid cells in the cultures remained low and conditioned medium
      prepared from IFN alpha-stimulated T, NK, and stromal cells was not cytotoxic to
      ALL blast cells. In contrast to results in freshly isolated ALL cells, six ALL
      cell lines tested were completely resistant to IFN alpha cytotoxicity. We
      conclude that IFN alpha is directly cytotoxic in most ALL cases but that the
      intensity of its effects varies widely among cases. The method used in this study
      may be applied to evaluate leukemic blast cell sensitivity to compounds with
      potential antileukemic activity, and to select patients to be entered in to
      clinical trials.

PMID- 8255099
TI  - Cross-resistance studies of folylpolyglutamate synthetase-deficient, methotrexate
      resistant CCRF-CEM human leukemia sublines.
AB  - CCRF-CEM human leukemia sublines resistant to short-term methotrexate (MTX)
      exposure as a result of decreased folylpolyglutamate synthetase (FPGS) activity
      were examined for their response to other cytotoxic agents. The R3/7 and R30dm
      sublines display 25 and 1%, respectively, of the FPGS activity of CCRF-CEM cells
      as measured with MTX in vitro. Response to agents in outgrowth experiments was
      examined under both continuous exposure (120 h, where MTX resistance is not
      observed) and short-term (6-14.5 h) exposure. During continuous exposure to
      various classes of agents, cross-resistance of R3/7 and R30dm that correlated
      with FPGS level was not observed, although some minor (< or = 3-fold) stochastic
      variations in sensitivity were noted. These agents included actinomycin D,
      Adriamycin, etoposide, vincristine, cisplatin, cytosine arabinoside, 5
      fluorouracil, and some other antifolates. Cross-resistance during continuous
      exposure that did correlate with FPGS level was noted, however, to glutamate
      containing thymidylate synthase inhibitors (including ICI D1694) and, to a minor
      extent, to 6-mercaptopurine and 5-fluorodeoxyuridine. Slight collateral
      sensitivity during continuous exposure that apparently correlated with FPGS level
      was noted to the lipid-soluble antifolate trimetrexate and to 5,8-dideazapteroyl
      L-ornithine, an FPGS-specific inhibitor. In short-term exposures (where MTX
      resistance of the sublines is observed), the resistant sublines displayed
      sensitivity or cross-resistance to each agent that was qualitatively similar to
      that observed for the same agent in continuous exposure. Because of the
      requirement for reduced folates in the anti-DNA mechanism of action of
      fluoropyrimidines and the current clinical use of leucovorin (LV) to enhance
      their effects, the interaction of LV and fluoropyrimidines was examined. The
      results suggest that even highly FPGS-deficient cells are as sensitive to the
      effects of LV modulation as are wild-type cells even at fluoropyrimidine exposure
      times as short as 4 h.

PMID- 8255100
TI  - tal-1 deletions in T-cell acute lymphoblastic leukemia as PCR target for
      detection of minimal residual disease.
AB  - Polymerase chain reaction (PCR) techniques based on amplification and
      identification of leukemia-specific DNA sequences provide a sensitive diagnostic
      method for detection of minimal residual disease (MRD) with a detection limit of
      10(-5) to 10(-6) (1-10 malignant cells in 10(6) normal cells). To date, the main
      leukemia-specific DNA sequences used as PCR targets in detection of MRD are
      breakpoint fusion regions of chromosome translocations and junctional regions of
      rearranged immunoglobulin (Ig) or T-cell receptor (TcR) genes. The recently
      identified tal-1 deletions involving the sil and tal-1 genes, provide a potential
      MRD-PCR target. tal-1 deletions are site-specific because they are mediated via
      recombination signal sequences homologous to Ig/TcR genes. In line with this
      homology, tal-1 deletions also show random insertion and deletion of nucleotides
      at their breakpoints, resulting in highly variable breakpoint fusion regions. The
      fusion region diversity can be applied to design patient-specific oligonucleotide
      probes. Our Southern blot analyses of a large series of 313 acute leukemias with
      a specific tal-1 deletion probe (SILDB) demonstrated that tal-1 deletions
      exclusively occur in T-cell acute lymphoblastic leukemia (T-ALL) and not in
      precursor B-ALL or acute non-lymphocytic leukemias. In addition, we did not
      detect tal-1 deletions in normal blood cells and normal thymocytes by PCR
      analysis. The diversity observed in tal-1 deletion fusion regions with an average
      insertion and deletion of approximately 7 and approximately 6 nucleotides,
      respectively, allowed us to design fusion-region-specific probes. The specificity
      of the fusion-region probes was proven and the detection limit of the MRD-PCR
      technique was tested in a series of dilution experiments. The observed detection
      limit of 10(-5) indicates that tal-1 deletions in T-ALL represent ideal leukemia
      specific PCR targets for detection of MRD.

PMID- 8255101
TI  - Inhibitors of tyrosine phosphorylation induce apoptosis in human leukemic cell
      lines.
AB  - Experimental evidence suggests that hematopoietic growth factors promote cell
      survival by suppressing apoptosis or programmed cell death. Since interleukin 3
      (IL-3) and granulocyte-macrophage colony stimulating factor (GM-CSF) induce
      tyrosine phosphorylation of a common set of proteins in the factor-dependent cell
      line M07e, we have investigated whether growth-factor-induced tyrosine
      phosphorylation is involved in the promotion of cell survival and suppression of
      apoptosis. Experiments were carried out with the leukemic cell lines HL-60 and
      M07e and the tyrosine kinase inhibitors genistein and tyrphostin AG82. Both the
      tyrosine kinase inhibitors induced apoptosis of HL-60 and M07e cells. This was
      indicated by the appearance of DNA degradation and morphologic evidence of
      nuclear condensation and fragmentation. It was also confirmed by flow cytometry
      of DNA, which showed apoptotic cells as a fraction of cells characterized by a
      diminished DNA stainability, represented on the DNA frequency histograms as a
      distinct peak below the G0/G1 population. Kinase inhibitors also reduced the
      fraction of cells in the S phase of the cell cycle. That tyrphostin specifically
      inhibited tyrosine kinases was further suggested by the prevention of its effects
      by the tyrosine phosphatase inhibitor sodium orthovanadate (vanadate), at least
      during the first 18-24 h of treatment. The incomplete prevention of genistein
      effects by vanadate suggests that genistein is a less specific inhibitor of
      tyrosine kinases than tyrphostin, and may also act as an inhibitor of
      topoisomerase II. Vanadate also prevented apoptosis and reduction of the S phase
      in M07e cells cultured for 24 h in the absence of growth factors. These results
      suggest that tyrosine phosphorylation is an essential step in IL-3 and GM-CSF
      signal transduction. Since in our experimental model the effects of tyrosine
      kinase inhibition and growth factor deprivation could be reversed by concomitant
      inhibition of tyrosine phosphatases, it is suggested that a balance between
      tyrosine kinases and tyrosine phosphatases establishes whether a cell will
      survive or undergo apoptosis.

PMID- 8255102
TI  - Soluble CD23 and other receptors (CD4, CD8, CD25, CD71) in serum of patients with
      chronic lymphocytic leukemia.
AB  - We measured the soluble (s) receptors CD23, CD8, CD4, interleukin-2 receptor (IL
      2R, CD25), and transferrin receptor (TfR, CD71), in normal serum and in patients
      with chronic lymphocytic leukemia (CLL) and evaluated them in relation to
      clinical and biological parameters of the disease, as well as serum
      immunoglobulin E (IgE). Compared to 31 normal individuals, 42 CLL patients had
      increased levels of sCD23 (98.4 +/- 127.7 versus 0.9 +/- 0.3 U/ml, p < 0.001),
      sIL-2R (6080 +/- 7030 versus 1420 +/- 640 pg/ml, p < 0.001), sTfR (12,100 +/-
      11,250 versus 5000 +/- 1050 ng/ml, p < 0.001), and sCD8 (510 +/- 191 versus 234
      +/- 89 U/ml, p < 0.001), but normal sCD4 levels. Mean sCD23 levels remained
      normal in patients with non-Hodgkin's lymphoma (other than small lymphocytic),
      Hodgkin's disease, hairy cell leukemia, acute lymphoblastic leukemia (ALL), acute
      myelogenous leukemia (AML), chronic myelogenous leukemia (CML), multiple myeloma,
      or solid tumors. Advancing Rai clinical stage was associated with a progressive
      elevation of sCD23 (p < 0.001), while sCD8 (p < 0.05), sIL-2R (p < 0.001), and
      sTfR (p < 0.005) were highest in stage 2 patients. Discriminant analysis
      confirmed the value of soluble receptor determinations in the clinical evaluation
      of CLL patients. sCD23 correlated with sIL-2R (p < 0.001) and sTfR (p < 0.05) but
      not with sCD4 or sCD8, and displayed an inverse relationship with serum IgE (NS)
      and total gamma-globulin (p < 0.05). sIL-2R correlated with sCD23 (p < 0.001),
      sTfR (p < 0.001), sCD4 (p < 0.01), and sCD8 (p < 0.01). The lymphocyte count
      correlated with serum lactate dehydrogenase (LDH) (p < 0.05), sCD23 (p < 0.001)
      and sIL-2R (p < 0.01) but not sTfR, sCD8, or sCD4. Chemotherapy produced
      consistent reductions of sCD23 levels in two responding patients. We conclude
      that: (i) sCD23 is considerably elevated in CLL, correlates with the tumor mass
      and clinical stage, and could be helpful in monitoring these patients; and (ii)
      sIL-2R, sCD8, and sTfR levels are less specifically increased and could be
      influenced by other factors such as immune activation and erythropoiesis.

PMID- 8255103
TI  - Autologous bone marrow transplantation with marrow purged by mafosfamide in seven
      patients with myelodysplastic syndromes in transformation (AML-MDS): a pilot
      study.
AB  - Seven patients with acute myeloblastic leukemia (AML) occurring on
      myelodysplastic syndromes (MDS) were consolidated while in complete remission
      (CR) by autologous bone marrow transplantation (ABMT) with a marrow purged in
      vitro by mafosfamide. The median age of population was 44 years (range 39-55).
      MDS FAB diagnosis was established before progression to AML in five patients:
      refractory anaemia with excess of blast (RAEB) in three patients, RAEB in
      transformation (RAEB-t) in one patient, and chronic myelomonocytic leukemia
      (CMML) in one patient. In the remaining two patients, the diagnosis of MDS (as a
      secondary malignancy in one) was made retrospectively at time of overt AML. Three
      out the seven patients had karyotypic abnormalities. The median interval between
      the obtention of CR and ABMT was 7 months (range 6-18). One patient died from
      transplant related toxicity. Engraftment occurred at a median of 41 days (range
      27-60), for white blood cells (> 10(9)/l) and 120 days (range 60-180) for
      platelets (> 50 x 10(9)/l). Four patients relapsed at 2.5, 6.8, and 25 months
      post-ABMT. Two patients are alive and well at 10 and 28 months, respectively.
      ABMT with marrow purged by mafosfamide is feasible in patients with AML following
      MDS with a prospect of cure. However, further studies are needed to assess the
      real value of this approach.

PMID- 8255104
TI  - Isolation and characterization of an early T-helper/inducer cell line with a
      unique pattern of surface phenotype, constitutive cytokine secretion and myc
      oncogene expression.
AB  - The cell line AG-F was isolated from the marrow of a neuroblastoma patient
      undergoing myeloablative treatment and autologous bone marrow rescue. A year
      later, the patient developed a Hodgkin's type lymphoma. AG-F cell line
      demonstrated an unusual phenotype, lacking surface CD2 and CD3, but expressing
      high levels of CD4, CD5, CD7, CD29, and CD45RO. Markers associated with Hodgkin's
      lymphoma cells, CD15 and CD30, were also positive. AG-F cells grow in suspension
      in clusters of 50-200 cells, with a doubling time of 9 h. They can also grow in
      serum-free medium and form tumors in nude mice. AG-F cells have amplified N-myc
      and c-myc and high levels of the corresponding mRNA transcripts. Cytogenetic
      analysis revealed a DNA index by flow cytometry of near tetraploid cells and a
      karyotype of 85-87 chromosomes, with consistent abnormalities in chromosomes 1,
      5, and 9. Gene rearrangement studies revealed rearrangement of the beta gene of
      the T-cell receptor. AG-F cells secrete high levels of IL-6, IL-8, IL-10, and GM
      CSF. Cell adherence and formation of long processes could be induced by
      fibronectin and were enhanced by exposure to PMA. Cells exposed to phorbol
      myristate acetate (PMA) had increased expression of CD11a, CD11b, CD18, CD45RO,
      and HLA-DR, whereas expression of CD15 and CD30 was markedly decreased.
      Similarly, the level of c-myc and N-myc oncoproteins and the levels of the
      cytoskeletal proteins, actin, tubulin, and vimentin markedly decreased early
      after PMA-induced differentiation.

PMID- 8255105
TI  - Expression of identical E2A/PBX1 fusion transcripts occurs in both pre-B and
      early pre-B immunological subtypes of childhood acute lymphoblastic leukemia.
AB  - The translocation t(1;19)(q23;p13) in pediatric patients with acute lymphoblastic
      leukemia (ALL) was demonstrated in early reports to result in a consistent fusion
      between the E2A and PBX1 gene sequences and in the expression of a uniform,
      chimeric E2A/PBX1 mRNA with transforming potential. More recent observations
      suggested that cytogenetically identical t(1;19) translocations can result in the
      transcription of different mRNA species and that expression of the E2A/PBX1
      message may be restricted to patients with the t(1;19) who display a pre-B
      phenotype of ALL. To further assess the correlation between the immunologic
      subtypes of the disease and specific genetic alterations, we have performed
      cytogenetic and molecular analyses in 221 children with B-lineage ALL. Expression
      of the chimeric E2A/PBX1 message was detected in 21 patients. Out of 14 patients,
      in whom cytoplasmic immunoglobulin (cig) analyses were available, no less than
      four had a cig- B-cell precursor ALL, whereas 10 displayed a cig+ B-ALL
      immunophenotype. These findings are at variance with a recent report in which
      expression of the E2A/PBX1 message was linked exclusively to a subset of patients
      who displayed a cig+ pre-B-cell precursor phenotype of ALL. In seven cases
      diagnosed before 1986, cig analyses were not available, and consequently E2A/PBX1
      expression could not be correlated to a particular immunological subtype of B
      cell precursor ALL. Our results have important implications for the detection of
      residual disease in pediatric patients where expression of the typical E2A/PBX1
      mRNA may occur both in cig+ (pre-B) and cig- (early pre-B) immunologic subtypes
      of ALL.

PMID- 8255106
TI  - Molecular characterization of the t(14;19)(q32;q13) translocation in chronic
      lymphocytic leukemia.
AB  - The t(14;19)(q32;q13) is a recurring translocation found in leukemic cells of
      some patients with chronic lymphocytic leukemia (CLL). The BCL3 gene was
      identified on chromosome 19 adjacent to the breakpoint of the translocation, and
      has been proposed to be a candidate proto-oncogene which may play a role in
      leukemogenesis. The current study of a Japanese patient with CLL revealed that
      the (14;19) is reciprocal at the molecular level; the BCL3 gene was juxtaposed to
      the 5' side of the S alpha 1 switch region of the immunoglobulin heavy chain gene
      (IGH) on the der(14) chromosome, and the IGH gene 5' to the S alpha 1 region was
      joined to chromosome 19 sequences on the der(19) reciprocal partner chromosome.
      The breakpoint on chromosome 19 was 16 kb upstream of the first exon of the BCL3
      gene and 7 bp of chromosome 19 sequences were deleted at the point of the
      junction. The t(14;19) translocations so far molecularly analyzed consistently
      occurred within one of the two S alpha switch regions; however, sequence analysis
      of the chromosome 19 regions involved in the translocation failed to demonstrate
      an obvious sequence similarity with the switch region. The chromosomal breaks on
      chromosome 19 from two CLL patients having the t(14;19) were within Alu repeated
      sequences.

PMID- 8255108
TI  - Is acquired idiopathic sideroblastic anemia (AISA) a disorder of mitochondrial
      DNA?

PMID- 8255107
TI  - Transitional pre-B-cell acute lymphoblastic leukemia of childhood is associated
      with favorable prognostic clinical features and an excellent outcome: a Pediatric
      Oncology Group study.
AB  - The presenting characteristics and survival of children with the newly recognized
      transitional cell pre-B immunophenotype of acute lymphoblastic leukemia (ALL) are
      compared with those of children with pre-B ALL to determine the clinical
      significance of the new phenotype. Patients with transitional pre-B ALL (n = 17),
      defined by lymphoblasts expressing cytoplasmic and surface mu heavy chains
      without kappa or lambda light chains, have lower initial leukocyte counts (p =
      0.02) and a higher frequency of DNA indexes > 1.16 (p < 0.001) than patients with
      pre-B ALL (n = 501), whether or not cases with the unfavorable prognostic (1;19)
      translocation are included in the analysis. Patients with transitional pre-B ALL
      lack FAB L3 morphology, bulky extramedullary disease, surface kappa or lambda
      chains, and the (8;14), (8;22), and (2;8) translocations, features that
      characterize the syndrome of B-cell ALL. The 4-year relapse-free survival result
      for children with transitional pre-B ALL appears better than that for children
      with pre-B ALL (93.3 +/- 17% versus 72.9% +/- 4.6%), but this difference is not
      statistically significant. We conclude that patients with transitional pre-B ALL
      have a very favorable prognosis in the context of the therapy used in this study.

PMID- 8255109
TI  - [Analysis of the geographic distribution of the incidence of diabetes mellitus
      type I in Catalonia].
AB  - BACKGROUND: The aim of the present study was to evaluate the geographic
      distribution of the incidence of diabetes mellitus type I (DMI) in Catalonia from
      1987-1990. METHODS: The base of the study is the Catalonian registry of incidence
      of DMI in the period from 1987-1990. The definition criteria were: diagnostic
      criteria of diabetes (WHO norms 1985), age of diagnosis under 30 years, residence
      in Catalonia in the period of diagnosis and exclusion of other types of diabetes.
      The population at risk was estimated according to the general census of the
      population of 1986. The total incidence of Catalonia was calculated by provinces
      and counties according to the Poisson distribution. RESULTS: The incidence of DMI
      observed in Catalonia was of 11.5/100,000 inhabitants per year (CI 95%, 10.6
      12.4) in the age group from 0-14 years and 10.7/100,000 inhabitants per year (CI
      95% 10.1-11.3) in the age group from 0-29 years. The exhaustivity in the
      detection of the cases was of 90.3%. No differences were found in interprovincial
      incidence in the 0-14 age group: Barcelona 11.6 (10.6-12.7), Girona 10.2 (7.2
      13.4), Lleida 11.7 (7.7-15.8), Tarragona 10.5 (7.6-13.5). In the 15-29 age group
      a lower incidence was observed in Tarragona. The incidence by counties varied
      between 2.9 and 15.0/100,000 inhabitants per year with those of greatest
      incidence being observed in the Valles Oriental (15.0/100,000 inhabitants/years),
      Alt Penedes (14.5/100,000 inhabitants/year), Segria (15.0/100,000
      inhabitants/year) and the Priorat (13.7/100,000 inhabitants/year). CONCLUSIONS:
      No differences were found in the incidence of diabetes mellitus type I in the
      four Catalonian provinces. Distribution by counties was more heterogeneous
      without defining zones with a much higher incidence to that observed in the whole
      of Catalonia.

PMID- 8255110
TI  - [Mortality from pleural mesothelioma in the province of Barcelona].
AB  - BACKGROUND: Pleural mesothelioma is a tumor of low incidence whose relation with
      the exposure to asbestos has been widely demonstrated. This exposure is generally
      occupational, but may also be domestic and there is the possibility of
      environmental exposure. METHODS: By death certifications all the cases of death
      by pleural mesothelioma residing in the province of Barcelona from 1983-1990 have
      been identified. The rates of direct or indirect mortality (standardized by age
      and sex) (cause of standard mortality) for all the municipalities of the province
      with some case of mesothelioma over the period studied were calculated. The
      geographic localization of the companies using asbestos in the province of
      Barcelona has been obtained, being classified into 6 groups according to the
      productive subsector to which they belong. RESULTS: The rate of mortality per
      100,000 inhabitants from 1983-1990 was 0.83 for males and 0.47 for females. The
      calculation of the cause of standard mortality for the municipalities of the
      province has shown an statistically significant increase in the risk of pleural
      mesothelioma for El Prat de Llobregat (ratio of standard mortality: 355.1) and
      Cerdanyola (ratio of standard mortality 313.9) where the companies producing
      fibrocement are located. CONCLUSIONS: Part of the cases of pleural mesothelioma
      in the province of Barcelona may not be due to direct occupational exposure; thus
      there may be important domestic and/or environmental exposure.

PMID- 8255111
TI  - [Neuro-reflexotherapy intervention in the treatment of non specified low back
      pain: a randomized, controlled, double-blind clinical trial].
AB  - BACKGROUND: Nonspecific low back pain is a very common disorder for which no
      completely satisfactory treatment has been established. A randomized, double
      blind, controlled clinical trial was design to assess the efficacy of neuro
      reflexotherapic intervention in the treatment of this condition. METHODS: Ninety
      one patients with a confirmed diagnosis of nonspecific low back pain were
      referred for treatment from primary health care facilities in the Spanish
      National Health System. A total of 43 patients were assigned to the control group
      and 48 to the treatment group. Patients in the treatment group received a single
      neuro-reflexotherapic intervention. Patients in the control group underwent a
      similar procedure, although inappropriate zones were stimulated. Patients in both
      groups were allowed to continue drug and physiotherapy treatments prescribed by
      their general practitioners. According to the design the study was ended when
      statistically significant and clinically evaluable results were obtained in an
      analysis carried out half way through the study. RESULTS: Participants underwent
      clinical evaluations on three occasions: immediately prior to intervention,
      immediately after and on day 30 afterwards. Patients in the treatment group
      showed immediate clinically and statistically significant improvements (p <
      0.0001) in pain, muscular contracture and mobility, allowing them to discontinue
      pharmacological treatment and keeping them free of symptoms during the study
      period. CONCLUSIONS: According to results of this study, neuro-reflexotherapic
      intervention has proved to be an effective method for treating low back pain.

PMID- 8255112
TI  - [Treatment of chronic lumbar pain].

PMID- 8255114
TI  - [The new dictionary of the Royal Spanish Academy: its repercussion on the medical
      language].

PMID- 8255113
TI  - [Liver transplantation for the treatment of type I familial amyloidotic
      polyneuropathy].
AB  - The first liver transplantation carried out in Spain for the treatment of type I
      familial amyloidotic polyneuropathy (FAP I) is presented. The reason for the
      operation was based on the liver being responsible for the synthesis of abnormal
      transtirretin (TTR) constituting the peculiar amyloid of the disease. Following
      transplantation a rapid and noticeable decrease in abnormal TTR was observed and
      the evolution of the clinical picture after 18 months of surgery is favorable
      with progressive improvement of the neurologic symptoms and normal function of
      the graft. These encouraging results coincide with those of the Swedish group of
      Umea, the pioneer of this procedure.

PMID- 8255115
TI  - [Intrasellar herniation of cerebral parenchyma and optic chiasma].

PMID- 8255116
TI  - [Hepatitis B in gypsy children and adolescents].

PMID- 8255117
TI  - [Crohn's disease: treatment with methotrexate].

PMID- 8255118
TI  - [Acute pulmonary edema secondary to tocolytic treatment for premature labor in a
      twin pregnancy].

PMID- 8255119
TI  - [Autoimmune hemolytic anemia after 9 years of treatment with alpha-methyldopa].

PMID- 8255120
TI  - Effect of alpha-fluoromethylhistidine on brain histamine and noradrenaline in
      muricidal rats.
AB  - Rats maintained on a thiamine-deficient diet for 30 days showed mouse-killing
      aggression (muricide). Once the muricide tendency appeared, it remained during
      the entire experimental period, even after subsequent administration of thiamine
      hydrochloride for 30 days. The effect of alpha-fluoromethylhistidine (FMH) on
      muricide in this animal model was examined, and histamine and noradrenaline
      levels in several brain regions were measured. One hour after i.p. injection of
      200 mg/kg of FMH, muricide was completely abolished. Significant decrease in
      histamine levels was found in the hypothalamus, thalamus, amygdala, striatum and
      pituitary of muricidal rats. Thus, the central histaminergic neuron system may be
      involved in the suppressive mechanism of muricide. On the other hand, it is
      noteworthy that the noradrenaline level was significantly decreased only in the
      hypothalamus. In conclusion, it seems likely that the suppression of muricide
      induced by FMH was attributable to both inhibition of the histaminergic system
      and activation of the noradrenergic system.

PMID- 8255121
TI  - Effect of glycerol-induced acute renal failure on glutathione status and mitogen
      induced proliferation of rat splenocytes.
AB  - The mitogen-induced activation responses of rat splenic lymphocytes were
      determined for control and uremic rats. Lymphocyte activation was quantified by
      incorporation of [3H]thymidine. Glycerol-induced acute renal failure (ARF)
      inhibited the proliferation of both lipopolysaccharide (LPS)-induced B
      lymphocytes and concanavalin A (Con A)-induced T-lymphocytes by 80% and 87%,
      respectively. The decrease in [3H]thymidine incorporation in both the LPS- and
      con A-activated cells significantly correlates with increases in plasma urea and
      creatinine concentrations (r = 0.83). Total glutathione (GSH) concentration in
      the splenocytes was not significantly different in terms of GSH per 10(7) cell,
      although the overall GSH and the number of viable splenocytes were generally
      lower in the uremic rats. Determination of GSH-related enzymes (GSH S
      transferase, GSSG reductase and GSH peroxidase) in the spleen of control rats and
      rats with ARF showed little difference in the activities of these enzymes,
      although the GSSG/GSH ratio, which is an indication of oxidative stress, was
      significantly increased in the spleen of uremic rats. Incubation of normal
      splenocytes from control rats with uremic plasma obtained from rats with ARF also
      significantly decreased the proliferation responses. Metabolic inhibitors present
      in uremic plasma may contribute to the inhibitory action on mitogen-induced
      proliferation of B- and T-lymphocytes, although oxidative stress which occurs in
      ARF may itself be sufficient to affect the immune function.

PMID- 8255122
TI  - Involvement of oxygen free radicals in the action of BN 52021 (PAF antagonist) to
      limit myocardial infarct size.
AB  - The ability of a PAF antagonist, BN 52021, to limit myocardial infarct size in
      rat was assessed. Anesthetized rats were subjected to coronary artery ligation
      for 72 h and infarct size was measured macroscopically using TTC staining.
      Systolic blood pressure and ECG were monitored. BN 52021 (2.5 and 5 mg/kg i.v.)
      markedly reduced the infarct size, prevented the loss of R wave, an
      electrophysiological parameter of ischemic injury, reduced elevated serum MDA
      levels and demonstrated an inhibition of luminal-enhanced chemiluminescence.
      There was no marked change in glutathione peroxidase activity with BN 52021
      treatment measured at various time intervals after coronary artery ligation. The
      beneficial effect of BN 52021 on ischemic injury may be due to specific
      inhibition of PAF-induced activation of neutrophils and consequent decreased
      amount of cytotoxic reactive oxygen species.

PMID- 8255123
TI  - Antinociceptive effect of centrally administered endothelin-1 and endothelin-3 in
      the mouse.
AB  - The antinociceptive effects of centrally administered (i.c.v.) endothelin-1 (ET
      1) and endothelin-3 (ET-3) were studied in mice by the use of 3 experimental
      procedures: hot plate, tail flick and acetic acid writhing tests. ET-1 (0.625-5
      pmol/mouse) and ET-3 (2.5-25 pmol/mouse) produced statistically significant
      increase of the hot plate and tail flick latencies with duration of about 120
      min. ET-3 showed weaker antinociceptive effect. ET-1 inhibited acetic acid
      induced writhings with ED50 = 1.9 (1.1-2.7) pmol/mouse. With ET-3 a maximum
      effect of 45.2% suppression of the writhing response was achieved at 5
      pmol/mouse. The antinociception due to ET-1 and ET-3 was not antagonized by
      naloxone and is thus independent of endogenous opioid release.

PMID- 8255124
TI  - Antibody-induced alterations of Na+/K(+)-ATPase activity in rabbit red blood
      cells during experimental thyroglobulin immunization.
AB  - Thyroid hormone modulates cell membrane Na+/K(+)-ATPase. A detailed study of
      erythrocyte membrane Na+/K(+)-ATPase activity was carried out during experimental
      thyroglobulin immunization. During the process of immunization there was a sharp
      decline in Na+/K(+)-ATPase activity until the 98th day of immunization, when the
      thyroglobulin antibody titer was at its peak. This enzyme activity retained a
      lower level although a fall in antibody titer occurred up to the 147th day.

PMID- 8255125
TI  - Gastric emptying of radionuclide-labeled solid meal in beagle dogs using a
      scintigraphic method.
AB  - A scintigraphic method for in vivo radiotracers measurement is described to
      investigate the gastrointestinal emptying rate in beagle dogs. The proposed
      method has been applied to study the effect of a pharmacological compound in
      enhancing stomach emptying and involves the following steps: 1) 131I-labeled
      anion exchange resin grains preparation, as solid food markers to be ingested by
      the dogs; 2) continuous recording of gastric emptying evolution over a period of
      5 h with fast data-gathering instrumentation employing small size and light
      weight CsI scintillation detectors coupled to a photodiode, equipped with a lead
      shield and collimator; 3) comparison of results obtained with drugs to previous
      standard emptying curves. The purpose of this study was to evaluate the
      prokinetic activity of a recent synthesized compound (BIMU 1).

PMID- 8255126
TI  - Efficacy of two different intramuscular doses of dipyrone in acute renal colic.
      Cooperative Study Group.
AB  - A randomized multicenter clinical trial was designed to compare the efficacy and
      tolerance of two different intramuscular doses of dipyrone (1 g and 2 g) with
      those of the reference drug, diclofenac sodium (75 mg), in the treatment of acute
      renal colic. A total of 129 patients were included; 43 patients were alloted to
      receive dipyrone 1 g, 45 to dipyrone 2 g, and 41 to diclofenac. Evaluation of
      pain (100 mm visual analogue scale) was carried out at 10, 20, 30, 60 min and 2,
      4 and 6 h after drug administration. There were no significant differences
      between the three groups in terms of pain relief in the first 60 min, but
      dipyrone 2 g provided significantly more pain relief than diclofenac and dipyrone
      1 g from 60 min to 6 h after drug injection. It is concluded that dipyrone 2 g
      produced a longer lasting analgesic response than dipyrone 1 g in the treatment
      of renal colic.

PMID- 8255127
TI  - Calcium and skeletal muscle: a multiple regression on signal transduction
      mechanisms in burn trauma.
AB  - The novelty of applying three-dimensional graphic capabilities involving area and
      vector changes was used to understand variations in inositol derivatives and
      their comodulating influence on calcium (Ca2+) in skeletal muscle under the
      duress of burn trauma. Burn injury was achieved by scalding of predefined areas
      (0, 20% and 50%) on the dorsal and ventral surfaces of mice. At day 21, 45Ca2+
      influx and efflux procedures were performed. Through multiple regression, the
      dependency of intracellular Ca2+ was determined with respect to three
      polyinositol forms each representing independence simultaneously. The
      contribution of each of these parameters was assigned to a three-dimensional
      axis. Vector analysis determined the relationship of intracellular Ca2+ to each
      of the independent parameters in control, 20% and 50% burn groups. Such vector
      analysis allows for a clear visualization of the interrelationships that exist
      between secondary (viz, IP3) and tertiary (viz, Ca2+) messenger systems. This
      clear visualization may allow for a greater understanding of messenger systems
      that may lead to more effective treatment of the systemic effects of severe burn
      trauma.

PMID- 8255128
TI  - [Competition in health care--are the patients winners?].

PMID- 8255129
TI  - [Quality, competence and competition in laboratory medicine].

PMID- 8255130
TI  - [Unethical attempt to contact patients through health care services].

PMID- 8255131
TI  - [Alcoholism--a disease or vice? Reducing consumption is a must].

PMID- 8255132
TI  - [Evaluation of current rehabilitation activities. Problems and choice of
      methods].
AB  - The evaluation of rehabilitation potential is discussed in the context of the
      recent allocation by the Riksdag of substantial funds for rehabilitation
      purposes, a measure designed to generate savings to social insurance at least
      comparable to the allocation. In the article are discussed the difficulties
      involved in assessing the impact of such political measures, when at the same
      time the chances of people being able to return to work after extended sick leave
      are reduced owing to the recession. An evaluation model is presented which, in
      addition to variables related to monetary savings to the community, incorporates
      indicators capable of identifying gains due to a rehabilitation programme that
      are important determinants of the changes of target groups returning to a
      productive and meaningful life.

PMID- 8255133
TI  - [Utilization of resources in rehabilitation. Presentation of an assessment
      scale].

PMID- 8255134
TI  - [Leg and foot ulcers. Rapid healing and reduced number of amputations with
      improved treatment].

PMID- 8255135
TI  - [Foot ulcers in patients with diabetes. Preventive measures reduce the number of
      amputations].
AB  - Reports of preventive management resulting in reduction, by 50 percent or more,
      of the incidence of major amputation due to foot ulceration in diabetics have now
      been published from seven different localities, five in Europe (Umea, Kisa, Lund,
      London and Geneva) and two in the USA (Tucson and Louisville). The methods used
      to achieve the reduction are remarkably similar, being based on systematic check
      ups for incipient foot ulceration and its putative risk factors. In all three
      Swedish reports, the work has entailed close liaison with community health
      centres in the respective areas, which is considered to be of the utmost
      importance in reaching all diabetics at risk of foot ulcers. Another important
      prerequisite is a specialised foot clinic for diabetic patients in each area,
      where the skills of a chiropodist, a physician specialised in diabetes, an
      orthopaedic surgeon and an orthopaedic shoemaker are available.

PMID- 8255136
TI  - [Skills of nurses treating diabetics must be supported].

PMID- 8255137
TI  - [The man behind the syndrome: Sir Heneage Ogilvie. Described colonic pseudo
      obstruction].

PMID- 8255139
TI  - [Healthy and beautiful teeth can be the cause of bad heart].

PMID- 8255138
TI  - [Difficult diagnosis of coronary insufficiency].

PMID- 8255140
TI  - [Man lives only three times?].

PMID- 8255141
TI  - Alpha 1-adrenoceptors in neonatal rat cardiac myocytes: hypoxia alters the
      responsiveness of alpha 1A and alpha 1B subtypes.
AB  - We investigated the contribution of alpha 1-adrenoceptor subtypes to the
      chronotropic response to norepinephrine (NE) in cultured neonatal rat cardiac
      myocytes under normoxia and hypoxia. A dose-dependent negative chronotropic
      response was induced by NE in the presence of propranolol. Hypoxic exposure
      inverted the negative chronotropic response to NE to a positive one. All of these
      chronotropic responses were completely antagonized by prazosin. In normoxic
      conditions, the NE-induced negative chronotropic response was completely
      antagonized by WB4101 but only partially (55%) so by chloroethylclonidine (CEC).
      After hypoxic exposure, WB4101 partially antagonized the positive chronotropic
      response to NE (54%), while CEC completely suppressed the action of NE. Hypoxic
      exposure did not alter the number of alpha 1A- and alpha 1B-adrenoceptor subtypes
      as measured by [3H]prazosin binding following CEC treatment. These results
      indicate (1) that cultured neonatal rat cardiac myocytes contain both alpha 1
      adrenoceptor subtypes, i.e., alpha 1A and alpha 1B, and (2) that the predominant
      alpha 1-adrenoceptor subtypes mediating NE-induced chronotropy were altered by
      hypoxia.

PMID- 8255143
TI  - Competitive vs. noncompetitive blockade of epinephrine-sensitive GTPase activity
      in human platelets.
AB  - The manner of inhibition of the epinephrine-stimulated GTPase activity by
      phentolamine and yohimbine was studied in human platelet membranes. (-)
      Epinephrine(1-microM)-stimulated GTPase activity was inhibited concentration
      dependently by phentolamine and yohimbine with IC50 values of 150 nM and 25 nM,
      respectively. Addition of increasing concentrations of phentolamine shifted the
      concentration-response curve to (-)-epinephrine to the right in a parallel
      manner. Schild plot analysis gave a KB value of 13 nM and a slope factor of 0.99.
      Yohimbine inhibited the activity, on the contrary, in a noncompetitive fashion.
      This inhibition by yohimbine was reversible after thorough washing of the
      membranes.

PMID- 8255142
TI  - Scoparone O-demethylase assay is not useful to differentiate the effects of model
      inducers of cytochrome P-450 in rabbit and guinea pig liver.
AB  - Coumarin derivative, scoparone (6,7-dimethoxycoumarin), is regioselectively O
      demethylated into isoscopoletin (I) and scopoletin (S). This oxidation is
      inversely influenced by cytochrome P-450 inducers in the rat such as 3
      methylcholantrene (3-MC) and phenobarbital (PB). The I/S ratio is higher than 1.5
      with 3-MC treatment whereas it is lower than 0.5 with PB treatment. With regards
      to this contrasting effect, it has been suggested that the I/S ratio should be
      useful to differentiate between the effects of these types of inducers. We
      studied the consequences of in vivo PB and 3-MC treatment on scoparone
      biotransformation in guinea pig and rabbit. In these two species, at the basal
      state, scoparone biotransformation was enhanced in comparison to the rat.
      Moreover, in these untreated animals, two other metabolites were formed. After 3
      MC or PB treatment, scoparone metabolism is, in contrast to the rat,
      inappropriate to differentiate between the P-450 profile of other animals.

PMID- 8255144
TI  - Gossypol inhibits basal and estrogen-stimulated DNA synthesis in human breast
      carcinoma cells.
AB  - Estrogen stimulates the growth of hormone-dependent human breast cancer. Failure
      of chemotherapy frequently results from the development of multidrug resistance.
      Gossypol (GP), a naturally occurring toxin, inhibits the growth of various
      carcinoma cells. Thus, the effects of GP on 17 beta-estradiol (E2)-stimulated DNA
      synthesis were studied in two hormone-dependent human breast carcinoma cell
      lines: the wild-type MCF-7 and the multidrug-resistant MCF-7 Adr cells. Cells (5
      x 104/well) were cultured for 24 hrs in a chemically-defined, serum-free medium
      consisting of 1:1 mixture of Dulbecco's Modified Eagle's medium and Ham's
      nutrient mixture F12 (DMEM/F12) supplemented with insulin (5.0 micrograms/ml),
      transferrin (5.0 micrograms/ml), epidermal growth factor (EGF; 10.0 ng/ml) and
      antibiotics E2 (0 or 10.0 nM), GP (0, 2.5, 5.0, 10.0 or 20.0 microM) and bovine
      serum albumin (BSA; 0 or 0.1 mg/ml) were used as treatments in a factorial
      experimental design. Cells were treated for 24 hrs and finally pulsed with 3H
      thymidine (5.0 microCi/ml) for 3 hrs. E2 significantly stimulated 3H-thymidine
      incorporation in both MCF-7 and MCF-7 Adr cells. GP at 10.0 and 20.0 microM
      inhibited both basal and E2-stimulated DNA synthesis in human breast cancer
      cells. The inhibitory effects of GP at 10.0 microM, but not at 20.0 microM, were
      blocked by BSA treatment. Results from the present study indicate that GP
      treatment was antiproliferative in both drug-sensitive and multidrug-resistant
      cancer cells and that the antiproliferative effects of GP on human breast cancer
      cells were mediated through mechanisms independent of estrogenic responses. Thus,
      GP could be potentially very useful for treatment of human breast cancer
      patients, especially those who have developed multidrug resistance.

PMID- 8255146
TI  - Effect of peritoneal and gastric irrigation with ozonated saline on arterial and
      venous blood gas values.
AB  - Ozone, a proven in vitro antiseptic agent, has been shown in vivo to reduce
      infectious morbidity when used as a lavage solution in rodent fecal peritonitis.
      As concern that absorption of hydroxyl radical byproducts of ozone breakdown
      might be deleterious to blood buffering capacity, the effects of a 5 minute
      intragastric or peritoneal lavage with ozonated saline on rodent arterial and
      venous blood gas values were determined. Compared to values obtained following
      lavage with oxygenated saline or normal saline, ozonated saline irrigation
      produced no appreciable alterations in arterial or venous pH, pO2, and pCO2 over
      a 1 hour observation period. Short-term ozonated saline peritoneal lavage does
      not appreciably effect rodent blood buffering capacity.

PMID- 8255145
TI  - Diminished muscarinic receptor-stimulated [3H]-PIP2 hydrolysis in Alzheimer's
      disease.
AB  - The functional integrity of the cortical muscarinic receptor (MR)-mediated
      phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C signalling
      pathway was assessed in Alzheimer disease (AD) and age-matched control subjects.
      There was no difference in the basal hydrolysis of [3H]-PIP2 to [3H]-inositol
      phosphates between control and AD membrane preparations. However, muscarinic
      agonist-stimulated PIP2 hydrolysis was significantly diminished in the AD cases.
      Diminished agonist-stimulated PIP2 hydrolysis correlated with the loss in high
      affinity agonist binding (KL/KH ratio) to the M1 muscarinic receptor subtype in
      the disease. These data further support the hypothesis that muscarinic receptor
      mediated signal transduction is altered in AD, and that the defect lies at the
      level of muscarinic receptor-G protein/effector coupling.

PMID- 8255147
TI  - Adrenoceptor coupling mechanisms which regulate salivary secretion during aging.
AB  - In parotid slices and membranes from Wistar rats 2, 12 and 24 months old, changes
      are noted in adrenoceptor-stimulated K+ fluxes, formation of [3H]inositol
      phosphates ([3H]IPs), cAMP production, and membrane environment. Norepinephrine
      stimulated K+ efflux and formation of [3H]IPs in the slices proceed through an
      alpha 1-adrenergic mechanism and are reduced 20% and 40% during aging,
      respectively. In beta-adrenoceptor stimulation with isoproterenol, no age changes
      were observed in K+ influx and cAMP production. The cholesterol content in
      membranes was reduced with age; concomitantly, the membrane viscosity decreased
      with age. These results indicate that the alterations in the membrane environment
      may provide age-dependent modulation of alpha 1-adrenoceptor coupling mechanisms
      and their functions.

PMID- 8255148
TI  - [125I]PIP HOE 140, a high affinity radioligand for bradykinin B2 receptors.
AB  - A high affinity radioligand for bradykinin B2 receptors was prepared by coupling
      an activated ester of [125I]4-iodobenzoic acid to the amino terminus nitrogen of
      the potent B2 antagonist HOE 140. The ligand, [125I]para-iodophenyl HOE 140
      ([125I]PIP HOE 140), bound to a homogeneous set of sites in guinea pig ileal
      membranes with an equilibrium dissociation constant of 15 pM and a maximal
      binding density of 193 fmole/mg protein. Competition studies with a number of BK
      related peptides indicated that the ligand specifically labeled B2 receptors in
      the preparation. The results suggest that [125I]PIP HOE 140 will be a useful tool
      for future studies of B2 receptors.

PMID- 8255149
TI  - Intrathecal catheterization alone reduces autotomy after sciatic cryoneurolysis
      in the rat.
AB  - There is substantial evidence that sciatic cryoneurolysis (SCN, freeze lesion of
      the sciatic nerve) is a neuropathic pain model in the rat. During
      characterization of this model, SCN was performed 4 days after either a sham
      operation or the insertion of an indwelling intrathecal catheter preparatory to
      selective spinal drug administration. Body weight and autotomy scores were
      recorded for the next 22 days until sacrifice. The catheter group experienced
      significant weight loss (7.5%) by 4 days but rapidly regained to parity with the
      sham group. Autotomy scores and the frequency of severe autotomy (score > 3) were
      less at day 22 in the catheter group as compared with the sham-control group (p <
      0.005, p < 0.03, respectively). Intrathecal catheterization itself effects the
      degree of behavioral response to neurogenic pain and thus, should be controlled
      for in studies using nociceptive animal models.

PMID- 8255150
TI  - The effects of an interferon inducer, polyriboinosinic polyribocytidylic acid on
      cytochrome P-450 dependent hepatic progesterone metabolism.
AB  - A time course study on the effects of an interferon inducing agent,
      polyriboinosinic polyribocytidylic acid (poly rIrC) on the hepatic cytochrome P
      450 dependent progesterone metabolism was performed. Administration of a single
      dose of poly rIrC (10 mg/kg i.p.) to adult male Wistar rats caused a time
      dependent effect on liver weight, microsomal protein and total cytochrome P-450
      levels, as well as the 16 alpha and 6 beta hydroxylation of progesterone. The
      response was multiphasic, with a maximal depression of both hydroxylase activity
      48 hours post-injection, followed by enhanced activity at 72 hours and subsequent
      return to control activity twenty-four hours later. A second less dramatic rise
      in the activities followed, bringing the 16 alpha and 6 beta hydroxylase activity
      to 159% and 141% of their respective control values by 336 hours, at which point
      of time, the trend appeared to be still on the rise. The enhanced activity at 72
      hours was preceded by an increase in serum cortisol and corticosterone levels,
      the ability of which to enhance the activity of 6 beta hydroxylation of steroids
      may partly explain the phenomenon.

PMID- 8255151
TI  - Intrahypothalamic, but not hippocampal, administration of muscimol suppresses
      hyperglycemia induced by hippocampal neostigmine in anesthetized rats.
AB  - We investigated the effects of intrahypothalamic or hippocampal injection of GABA
      receptor agonists on hyperglycemia induced by hippocampal neostigmine. Prior to
      the injection of neostigmine (50 nmol) into the hippocampus (HPC), muscimol (0.01
      1 nmol) or baclofen (1 nmol) was injected into the bilateral ventromedial
      hypothalamus (VMH). Muscimol suppressed the hyperglycemia in a dose-dependent
      manner, but baclofen affected it only minimally. In contrast, neither hippocampal
      muscimol (1 or 2.5 nmol) nor baclofen (1 nmol) suppressed the hippocampal
      neostigmine-dependent hyperglycemia. Intrahypothalamic muscimol (1 nmol) also
      decreased the changes in hepatic venous plasma glucagon and epinephrine
      significantly. These results indicate that intrahypothalamic muscimol suppresses
      hyperglycemia caused by cholinergic neurons originating from the HPC, indicating
      existence of the location specificity.

PMID- 8255152
TI  - Characterization of substantia nigra pars reticulata neurons based on response to
      iontophoretically applied GABA and flurazepam.
AB  - Previous work had suggested that neurons in the pars reticulata of the substantia
      nigra (SNpr) might be differentiated based on responsiveness to GABA and
      benzodiazepines (BZs). To evaluate this possibility, multi-barreled glass
      capillary assemblies were used to examine the effects of GABA and a BZ,
      flurazepam (FZP), on the spontaneous activity of single SNpr neurons in chloral
      hydrate anesthetized rats. Both FZP and GABA, as a function of increasing
      ejection current, decreased the rate of neuronal discharge. SNpr neurons differed
      according to the maximum effect of each agent. For over half of the cells, the
      spontaneous discharge could be inhibited at least 90% by GABA, while the maximum
      FZP effect in the same cells ranged from 20 to 100% inhibition. Except for 3
      neurons, the maximum inhibition produced by GABA was about the same or greater
      than that produced by FZP. No clear anatomical segregation according to BZ effect
      was found.

PMID- 8255153
TI  - Immune cells mediate epinephrine secretion from bovine chromaffin cells in vitro.
AB  - Potential immunological influences on peripheral catecholamine secretion were
      investigated by measuring epinephrine secretion from chromaffin cells in vitro in
      response to cell-free conditioned media from mononuclear cells. Chromaffin cells
      were isolated from bovine adrenals whereas mononuclear cells were isolated from
      bovine spleen tissue or whole bovine blood. In secretion experiments epinephrine
      release and epinephrine remaining in cells was determined such that secretion was
      expressed as % of total cell content. After 90 minutes exposure to conditioned
      media, 22.8 +/- 1.1% of content was released compared to 1.7 +/- 0.2% with RPMI
      media. Secretion after filtration (< 3,000 MW cutoff) was 21.6 +/- 0.9% whereas
      after boiling and boiling in acid, secretion was 10.2 +/- 0.2 and 4.3 +/- 0.1%
      respectively. Dialysis (< 3,000 MW cutoff) reduced the 90 min conditioned media
      stimulated epinephrine secretion from 22.5 +/- 3.8% to 2.3 +/- 0.3%. Neither
      atropine nor hexamethonium blockade altered the conditioned media-stimulated
      epinephrine secretion. These results suggest that mononuclear cells produce a low
      molecular weight substance--most likely a peptide--that contributes to the
      stimulation of epinephrine secretion.

PMID- 8255154
TI  - The association of age and current world cancer mortality rates in relation to a
      century of cancer deaths in the U.S.
AB  - Recent data from a variety of countries and from the individual states in the US
      show that the annual cancer death rate is highly correlated with the percentage
      of the population aged 60 or more years. Historical data for the United States
      over the period 1900-1990 reveal that the percentage of its population > or = 60
      yrs increased with a corresponding increase in the annual cancer death rate. When
      the US data over this time period are viewed against the current world data and
      the current individual state data there is a striking similarity, thereby
      demonstrating that the current world and state cancer mortality values provide an
      accurate historical picture of the US cancer death rate over almost a century.

PMID- 8255155
TI  - Pharmacologic modulation of Th1- and Th2-associated lymphokine production.
AB  - Murine helper T cells can be divided into at least two groups, Th1 and Th2, based
      on the patterns of lymphokine secretion after antigenic or mitogenic stimulation.
      Recently, a similar subdivision was proposed in the human situation.
      Interestingly, the different patterns of lymphokine production correlate with
      different effector functions of the Th subpopulations. Th1 cells appear to
      dominate delayed type hypersensitivity reactions. Conversely, Th2 cells dominate
      the immune response to allergens and probably play an important role in allergic
      disorders. One of the clinical manifestations in which Th2 cells appear to
      dominate the immune response is allergic asthma. The mainstay of therapy in
      asthmatic persons is formed by glucocorticoid and beta-adrenoceptor agonist
      treatment. A differential pharmacological modulation of the lymphokine production
      by Th1 and Th2 cells can be of therapeutic relevance in allergic diseases in
      which an inappropriate balance between Th1 and Th2 cells exists. Such a
      differential modulation may underlie the beneficial usage of glucocorticoids and
      beta-adrenoceptor agonists in the treatment of asthma. The present report
      summarizes the effects of glucocorticoids and cAMP modulating agents on the
      activation and lymphokine production of T lymphocytes and Th subsets.
      Additionally, the effect of other steroid hormones is evaluated.

PMID- 8255156
TI  - Utilization of aspirin, quinine and verapamil in the prevention and treatment of
      scorpion venom intoxication.
AB  - Aside from serotherapy, the treatment of scorpion venom intoxication is
      symptomatic. The aim of this study was to compare the efficacy of drugs usually
      used in scorpion venom intoxications (atropine, propranolol) to that of other
      compounds, chosen in light of the pathophysiology of scorpion venom intoxication:
      dipyridamole, doxapram, quinine formate, lysine-acetyl-salicylate, valproate and
      verapamil. Using mice, the parameters evaluated were the preventive and
      therapeutic effects of drugs during experimental venom intoxication by
      Androctonus australis Hector and one of its toxins AaH 1, and by Buthus occitanus
      and Tityus serrulatus tunetanus on the other hand. It was found that although
      most of the drugs used could prolong the survival of the animals, the
      administration of verapamil and more so that of aspirin or quinine formate led to
      a 50 to 100% loss of venom and toxin toxicity, depending on the drug and the
      origin of the venom. In the case of propranolol, doxapram, atropine, dipyridamole
      and valproate, no or little protection were observed. If these results are
      confirmed in humans, the systematic use of these drugs could be a simple means
      for treating scorpion venom intoxication. The problem of scorpion venom
      intoxication poses a health problem both in the North African Maghreb and in the
      Americas. As a result of considerable information campaigns, the number of
      scorpion venom intoxications in Tunisia has dropped from 3000 in 1967 to 1000 per
      year in the 1980s. Serotherapy has reduced mortality to 0.35%, most deaths
      occurring in underweight children. In light of the large number of countries in
      which there is a risk of scorpion venom intoxication in the summertime, however,
      its prevention and treatment remain a major problem.

PMID- 8255157
TI  - Effects of calcium channel entry blockers on cocaine and amphetamine-induced
      motor activities and toxicities.
AB  - The effects of calcium channel entry blockers on cocaine and amphetamine-induced
      behavioral responses were investigated. Cocaine and amphetamine produced dose
      dependent increases in locomotor activity and stereotyped behavior with a maximum
      response at 40 and 1.2 mg/kg, respectively. The 1,4-dihydropyridine nimodipine
      and the benzothiazepine diltiazem were more effective in inhibiting cocaine (20
      mg/kg)-induced responses than amphetamine (0.6 mg/kg)-induced responses. At doses
      of cocaine and amphetamine that caused seizures and death, nimodipine,
      nitrendipine and diltiazem did not offer any protection; rather, they potentiated
      the toxicities produced by these psychomotor stimulants.

PMID- 8255158
TI  - The modulatory effects of mu and kappa opioid agonists on 5-HT release from
      hippocampal and hypothalamic slices of euthermic and hibernating ground
      squirrels.
AB  - To elucidate the role of opioids in regulating hibernation, the modulatory
      effects of different opioids on 35 mM K(+)-stimulated [3H]-5-HT release from
      brain slices were examined in the Richardson's ground squirrels. DAGO ([D-Ala2,N
      Me-Phe4,Gly-ol5]-enkephalin), a specific mu agonist, evoked a significant dose
      dependent (10(-7)-10(-5) M) inhibition of K(+)-stimulated 5-HT release from
      hippocampal slices of the non-hibernating squirrels. The inhibitory effect of
      DAGO was attenuated by either the opioid antagonist naloxone (10(-6) M) or the
      voltage dependent sodium channel blocker tetrodotoxin (TTX, 10(-6) M). The
      inhibitory effect of DAGO persisted in the hibernating squirrels; however, a ten
      fold higher concentration of DAGO (10(-6)-10(-5) M) was required to elicit a
      significant inhibition. In contrast, kappa agonist U50488 (10(-5) M) exerted a
      significant enhancement of K(+)-stimulated 5-HT release from hippocampal slices
      of the non-hibernating squirrels. This enhancement was blocked by either the
      specific kappa antagonist nor-binaltorphimine (10(-6) M) or TTX (10(-6) M).
      However, in the hibernating squirrels, the stimulatory effect of U50488 (10(-5)
      M) on 5-HT release was absent. DAGO and U50488 had no modulatory effects on K(+)
      stimulated 5-HT release from the hypothalamic slices of either the non
      hibernating or hibernating squirrels. These results demonstrate that the
      modulatory effects of opioids on 5-HT release are receptor-specific and state
      dependent, indicating the complex nature of the roles of different opioids in
      regulating hibernation.

PMID- 8255159
TI  - Normal thrombin binding leads to greater fibrinogen binding and increased
      platelet aggregation in spontaneously hypertensive rats.
AB  - This study was conducted to determine the mechanisms of increased platelet
      reactivity to thrombin in hypertension. Thrombin induced significantly greater
      platelet aggregation in spontaneously hypertensive (SHR) than in normotensive
      (Wistar Kyoto, WKY) rats. Fibrinogen and thrombin binding to platelets was
      determined using [125I]-fibrinogen and [125I]-thrombin respectively. Increased
      platelet aggregation in SHR correlated with thrombin-induced greater binding of
      fibrinogen to SHR than to WKY platelets. However, the number of thrombin
      receptors (binding sites/platelet) in WKY (19,500 +/- 3,000) and SHR (23,100 +/-
      3,000) as well as thrombin dissociation constants were statistically similar in
      WKY (1.17 +/- 0.2 microM) and SHR (1.62 +/- 0.27 microM) platelets. Fura 2/AM, a
      fluorescent calcium indicator, loaded platelets were used to quantify the
      platelet ionized calcium ([Ca2+]i). The [Ca2+]i in unstimulated SHR and WKY
      platelets was essentially the same. In a calcium poor medium, thrombin-induced a
      35% greater increase in [Ca2+]i in SHR than in WKY platelets. These data, taken
      together with our earlier observations that thrombin induces a significantly
      greater hydrolysis of phosphoinositide (Thromb. Res. 49, 5-21, 1988), lead us to
      suggest that thrombin-induced increased generation of inositol 1,4,5
      trisphosphate and diacylglycerol induces greater fibrinogen binding and
      consequently increased aggregation in SHR than WKY platelets. The finding that
      the thrombin binding isotherms are similar in WKY and SHR platelets suggests that
      increased platelet sensitivity to thrombin in hypertension may be due to altered
      signal transduction and not due to changes in the number or affinity of thrombin
      receptors.

PMID- 8255160
TI  - Metallothionein I reduction of cytochrome c.
AB  - Using absorption spectroscopy we have found that metallothionein I at
      concentrations as low as 1 microM reduces ferricytochrome c. This reduction is
      more potent than that of another abundant intracellular thiol, glutathione. Also,
      oxidation of ferricytochrome c which had been reduced by metallothionein I occurs
      more slowly than when the reductant was glutathione. Over a pH range of 6 through
      9 there is no variation in the initial rate of metallothionein I reduction of
      ferricytochrome c. These data demonstrate a potent interaction between
      metallothionein I and ferricytochrome c.

PMID- 8255161
TI  - Influence of bromocriptine administration to mothers on the development of pup
      thymocyte and splenocyte subsets and on mitogen-induced proliferation in the
      mouse.
AB  - The influence of prolactin (PRL) on the development of the immune system in the
      mouse was studied by injecting mothers with bromocriptine (CB-154) to produce
      hypoprolactinemic milk. Alterations in pup thymocyte and splenocyte cell subsets
      were observed to graded doses of CB-154 administered to mothers. There was an
      increase in the relative percentages of neonate thymic CD4 and CD8 cells at 5
      days of age when mothers were injected with 100 micrograms of CB-154 2 x daily
      from day 1 to 5 of lactation, however, there was no alteration in absolute thymic
      subset cell numbers. The relative percentage of pup spleen CD4, CD8 and B cells
      were increased when mothers were administered 50 or 100 micrograms of CB-154 and
      the 50 micrograms dose resulted in a significant increase in the absolute number
      of CD4 cells while the 100 micrograms dose induced a significant decrease in the
      three splenic cell subsets examined. Graded doses of CB-154 administered to
      mothers resulted in decreases in the PRL concentration of stomach milk as
      measured by the Nb2 cell proliferation assay. The serum PRL level of the pups,
      however, was not altered by any dose of CB-154 injected to the mothers. The
      administration of PRL to pups nursing mothers given the 100 micrograms dose of CB
      154 did not alter the pup thymocyte and splenocyte subset population from that of
      litter-mate controls. The administration of mouse PRL and mouse growth hormone
      antisera to pups nursing saline-injected mothers did not alter thymocyte and
      splenocyte subsets from that of saline-injected litter mate controls. The
      proliferation of neonatal thymocytes by Con-A stimulation was not altered by CB
      154 injection to mothers and PRL administration to pups. However, since the
      percentage of thymic CD4 and CD8 cells in the thymus was increased 2 to 3 fold,
      the apparent lack of effect was in fact a decrease in the responsiveness of the
      thymocytes. Con-A stimulation of neonatal splenocytes resulted in a significant
      increase in proliferation for mothers administered CB-154 in keeping with the
      increase relative percentage of CD4 and CD8 cells observed. Prolactin
      administration to the pups did not alter the response. LPS stimulation of
      neonatal splenocytes increased the proliferation of B cells taken from pup
      nursing mothers administered CB-154 and PRL administration appeared to partially
      block this proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8255162
TI  - Chlorinated dibenzo-p-dioxins and dibenzofurans and the human immune system. 1.
      Blood cell receptors in volunteers with moderately increased body burdens.
AB  - Using monoclonal antibodies (mAbs) and flow cytometry, we studied a variety of
      surface receptors on lymphocyte subpopulations of workers with moderately
      increased body burdens of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and of other
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/PCDF), expressed here
      as International-Toxicity Equivalencies (I-TE). The hypothesis to be tested was
      whether or not humans exhibit a similar susceptibility to PCDDs/PCDFs with
      respect to the surface receptors found previously to respond to small doses of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Callithrix jacchus. These are:
      helper-inducer (memory) T cells (CD4+CD45R0+CD45RA-CD29highCD11a+), CD20+ B
      cells, and cytotoxic T cells (CD8+CD56+/CD57+). Furthermore, 68 triple-labellings
      with mAbs were performed on the cells of each volunteer to possibly generate
      further hypotheses. It was evaluated whether any of the variables might be used
      as a biomarker of effects for this class of compounds. There were two main goals:
      (1) to evaluate whether workers with a moderately increased PCDD/PCDF-body burden
      [25-140 ppt TCDD or 104-522 ppt I-TE in blood fat] exhibit changes in the surface
      receptors of white blood cells, as observed in previous studies in non-human
      primates, and (2) to clarify whether persons at the upper range [10-23 ppt TCDD
      or 30-90 ppt I-TE in blood fat] of the body burden reference values of a not
      particularly exposed population show detectable deviations in these immunological
      variables, when compared with persons at the lower and medium range [1-3 ppt TCDD
      or 9-29 ppt I-TE] of these body burden reference values. Regression analysis of
      our data revealed slight trends for some of the biomarkers (e.g. CD45R0+). With
      one exception, these were all increases. None of the alterations observed are of
      medical relevance. The slight increase in the percentage of CD4+CD45R0+ cells
      remained significant even after covariant analysis taking age-related changes
      into account. Altogether, the data do not provide any evidence to support an
      assumption that moderately increased body burdens of PCDDs/PCDFs in adults induce
      decreases in the cellular components of the human immune system. Adult humans
      certainly are less susceptible to this action of PCDDs/PCDFs than adolescent
      Callithrix jacchus.

PMID- 8255163
TI  - Inhibition of cytokine production by a new inotropic agent, vesnarinone, in human
      lymphocytes, T cell line, and monocytic cell line.
AB  - Vesnarinone, a recently synthesized quinolinone derivative with positive
      inotropic properties, has been reported to improve survival of patients with
      congestive heart failure. However, the mechanisms that contribute to the
      increased survival are unknown. In this study, we showed vesnarinone had
      inhibitory effects on the production of tumor necrosis factor-alpha, interferon
      gamma, interleukin-1 beta and interleukin-2 by stimulated human peripheral blood
      mononuclear cells, human Jurkat T cell line and THP-1 monocytic cell line.
      Vesnarinone may exert its beneficial effect on patients with congestive heart
      failure, in part, by its immunomodulating activity.

PMID- 8255164
TI  - Effects of the ANF-C receptor ligand des[Cys105,Cys121]rANF(104-126) on ANF
      internalization and cGMP production by bovine pulmonary artery endothelial cells.
AB  - A role for the ANF-C receptor ligand des[Cys105,Cys121]rANF(104-126) in ANF
      receptor-effector coupling was investigated using cultured bovine pulmonary
      artery endothelial cells as a model system. The ligand was equipotent with
      rANF(99-126) in displacement of [125I]des[Cys105,Cys121]rANF(104-126) binding to
      whole cells and labelled only one population of ANF receptors as shown by
      affinity crosslinking experiments. In cells pretreated with des[Cys105,
      Cys121]rANF(104-126), internalization of [125I]rANF(99-126) binding was reduced
      and enhanced accumulation of cGMP was observed under basal conditions, or in the
      presence of a low concentration (0.1 nM) of rANF(99-126). These results provide a
      mechanistic basis for the observed enhancement of ANF-dependent vasodilation by
      ANF-C receptor selective ligands.

PMID- 8255165
TI  - Involvement of nitric oxide in noradrenaline-induced increase in blood flow
      through brown adipose tissue.
AB  - N omega-nitro-L-arginine methyl ester (L-NAME) (80 mg), a NO synthase blocker,
      completely abolished noradrenaline (NA)-induced increase in blood flow through
      brown adipose tissue (BAT) in the urethan-anesthetized rat. L-NAME suppressed NA
      induced increase in blood flow dose-dependently. L-arginine (80 mg), but not D
      arginine (80 mg), reversed the inhibitory effect of L-NAME (0.8 mg). NA-induced
      increase in BAT temperature was also decreased by L-NAME. These results suggest
      that nitric oxide mediates NA-induced increase in BAT blood flow.

PMID- 8255166
TI  - Preparation, characterization and release of microencapsulated bromodeoxyuridine.
AB  - Biodegradable and biocompatible microspheres with bromodeoxyuridine (BrUrd) have
      been prepared, characterized and tested in vitro and in vivo. Scanning electron
      microscopy and image analysis revealed regular spherical shapes and an average
      size +/- SD of 2.47 +/- 0.59 microns. Total content of BrUrd as determined by
      HPLC was within the range of 0.2-1.5%. Kinetic analyses of two different
      preparations showed similar release half-times (approx. 12 hrs), kinetic
      constants -0.0556, -0.0564, and -0.0557, -0.0597 [h-1], and correlation
      coefficients of 0.998, and 0.999 when fitted to the first order or biphasic first
      order kinetics, respectively. Preliminary data from immunocytochemical studies
      revealed efficient incorporation of BrUrd delivered from these microcapsules into
      nuclei of proliferating cells surrounding brain lesions in rats.

PMID- 8255167
TI  - Interaction of a doxorubicin-transferrin conjugate with isolated transferrin
      receptors.
AB  - It is shown that transferrin-doxorubicin conjugates bind to isolated transferrin
      receptors. The receptors were isolated from human full-term placenta by
      solubilization of trophoblast plasma membranes with the nonionic detergent C12E8
      and then by affinity chromatography on a diferric transferrin-coupled Sepharose
      CL-4B column. The binding affinity of such conjugate was similar to that of
      transferrin. Dissociation of conjugate from the isolated receptor occurred with
      time-dependent kinetics similar to those of transferrin when the experimental
      conditions mimicking the physiological steps of transferrin recycling were
      consecutively applied. These results support the idea that a) binding of such
      conjugates is primarily governed by the interaction between the transferrin part
      of the conjugates and the transferrin receptor, and b) it is not the transferrin
      receptor itself which participates in the putative secondary interaction between
      the receptor-bound conjugates and plasma membrane.

PMID- 8255168
TI  - Effect of ganglioside GM1 on arachidonic acid release in bovine aortic
      endothelial cells.
AB  - A role for the ganglioside GM1 in arachidonic acid release in bovine aortic
      endothelial cells (BAEC) was investigated. [3H]Arachidonic acid-labeled BAEC were
      preincubated with GM1 and incubated with one of four different stimulators. GM1
      inhibited arachidonic acid release when stimulated with maitotoxin or melittin
      but not with ionomycin or thapsigargin. A 10 microM GM1 concentration achieved a
      50% and 100% inhibition of the maitotoxin and melittin responses, respectively.
      The selective inhibition displayed by GM1 on the maitotoxin and melittin
      responses was not due to its ability to bind calcium since all four drugs,
      maitotoxin, melittin, ionomycin, and thapsigargin, required extracellular
      calcium. The effect of GM1 was not specific to arachidonic acid release. GM1 at
      50 microM inhibited phosphatidylinositol polyphosphate (PIP) hydrolysis mediated
      by melittin, but did not affect hydrolysis mediated by ionomycin. Moreover, the
      activity of GM1 was not restricted to phospholipid metabolism since it also
      inhibited calcium influx that was stimulated by maitotoxin or melittin but not by
      ionomycin. We conclude that GM1 is not a specific inhibitor of phospholipases in
      bovine aortic endothelial cells, but rather its activity is dependent on the type
      of stimulant used to activate the cell.

PMID- 8255169
TI  - In vitro femoral arterial responses to vasoconstrictor and vasodilator agents in
      endotoxin shock.
AB  - The hypothesis for this study is that the decreased arterial response to
      catecholamines may be due to the effect of endotoxemia on vessel tone. One
      control ring was taken from one femoral artery of a Wistar rat and after
      endotoxin (ENDT) infusion (i.v. 6 mg/kg-1 hr.), one ring was removed from the
      contralateral artery. The post-ENDT rings were tested in four groups which were
      determined by the mean arterial pressure (MAP) levels at the time of dissection:
      100 mmHg (120 min), 80 mmHg (270 min), 60 mmHg (300 min) or 40 mmHg (330 min).
      KCl, phenylephrine (PHE) and arginine-vasopressin (AVP) dose-response curves (DR)
      were obtained at a preload of 500 mg which allowed the maximum response in
      control rings. When compared at 500 mg preload the maximal active response to all
      agonists post-ENDT was decreased by about 50%. By increasing the preload on the
      ENDT rings to 800 mg, the active tension became 2.49 times the active tension of
      the control rings. Length-tension experiments also showed a greater response for
      post-ENDT rings and a greater preload at maximum response but the ring
      circumference was the same. In contrast the in vivo femoral artery diameters at
      90 min post-ENDT (100 mmHg) were 82.6% of control. Endothelium-dependent
      relaxation by acetylcholine (ACh) was abolished by ENDT but endothelium
      independent relaxation to nitroprusside (NP) was not affected. It is concluded
      that the resting tone and active tension of femoral artery smooth muscle is
      increased by ENDT and the decreased in vivo responsiveness to vasoconstrictor
      agonists may be the result of vessel constriction due to loss of endothelium. The
      results also suggest that in vitro comparison of vessels in studies of endotoxin
      shock be done at the same muscle length rather than at the same preload.

PMID- 8255170
TI  - Prodynorphin and vasopressin mRNA levels are differentially affected by chronic
      ethanol ingestion in the mouse.
AB  - Opioid peptides derived from the precursor, prodynorphin, are co-localized with
      vasopressin in the hypothalamus and posterior pituitary, and vasopressin and
      prodynorphin synthesis are coordinately regulated during salt-loading. We had
      previously found that chronic ethanol ingestion resulted in decreased levels of
      hypothalamic and extrahypothalamic vasopressin mRNA, and the current study
      investigated the effect of ethanol ingestion on prodynorphin mRNA levels. A cRNA
      probe was constructed from a PCR product amplified from mouse genomic DNA.
      Cloning and sequencing of the PCR product revealed that the sequence of the mouse
      prodynorphin gene used to synthesize the probe is highly conserved, with high
      sequence similarity to corresponding regions of the gene in other mammalian
      species. In situ hybridization using the cRNA probe showed a widespread
      distribution of prodynorphin mRNA in mouse brain. In dehydrated mice,
      prodynorphin mRNA was significantly increased in the hypothalamus and nearly all
      other brain areas examined. In ethanol-fed mice, prodynorphin mRNA was also
      significantly increased in hypothalamus (50-60%) and in most brain areas. In the
      same mice, measurement of hypothalamic vasopressin mRNA confirmed a significant
      (approximately 60%) decrease. These results indicate that hypothalamic
      vasopressin and prodynorphin mRNA can be differentially regulated in certain
      situations.

PMID- 8255171
TI  - Ontogeny, sex dimorphism, and neonatal sex hormone determination of synapse
      associated messenger RNAs in rat brain.
AB  - Sex hormones influence neurite outgrowth and synaptogenesis in certain hormone
      dependent areas of the rat brain during neonatal development. These alterations
      are thought to mediate changes in brain structure and function between the sexes.
      Growth-associated protein 43 kDa (GAP-43) gene expression is estrogen-regulated
      in the adult ventromedial hypothalamus (VMH) and sexually dimorphic (M:F = 1.8:1)
      in adult cortex (CTX). Such effects intimate hormonal regulation of synaptic
      plasticity. To investigate the nature of these dimorphisms, the present study
      examined the ontogeny of expression of mRNAs encoding 3 neural-specific proteins:
      GAP-43, SCG10, and synaptosomal-associated protein 25 kDa (SNAP-25); and
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in the VMH and CTX; and also
      the effects of altering the neonatal sex hormonal milieu on the development of
      these adult dimorphisms. Levels of specific mRNAs in VMH and CTX were quantitated
      by slot-blot hybridization in rats of both sexes at different postnatal ages. To
      determine the involvement of neonatal sex hormones on the levels of these mRNAs,
      male neonatal rat pups were treated with an estrogen receptor antagonist or an
      aromatase inhibitor, and neonatal female pups were treated with testosterone or
      estrogen prior to slot-blot evaluations in adulthood. In VMH, GAP-43 mRNA levels
      were high on days P1 and P4 with a 3-fold decrease by day P23; in CTX, GAP-43
      mRNA first increased by day P11, then fell to baseline by day P23. In VMH, SCG10
      mRNA showed only small increases with time; but in CTX, there was a 5-fold drop
      from days P4 to P23. In VMH, SNAP-25 mRNA was low and changed only slightly; but
      in CTX there was a 5-fold increase between days P4 and P60. At birth, there was
      no sex dimorphism in either VMH or CTX, but the levels of all 3 neural-specific
      mRNAs were sexually dimorphic in adult CTX (M:F = 1.76 for GAP-43, 1.46 for
      SCG10, 1.44 for SNAP-25). GAPDH mRNA levels were regulated developmentally in VMH
      and CTX, but there was no sex dimorphism in either area. In male rats who
      received either an estrogen antagonist or aromatase inhibitor at birth, the CTX
      GAP-43 and SNAP-25 mRNA levels fell by 30%, to levels similar to untreated
      females. Conversely, in female rats, neonatal treatment with either testosterone
      or estrogen increased GAP-43 and SNAP-25 mRNA levels by about 30%, to levels
      similar to the untreated adult male. SCG10 levels did not demonstrate neonatal
      hormonal dependence.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8255172
TI  - Modulation of the phospholipase C activity in rat brain cortical membranes by
      simultaneous activation of distinct monoaminergic and cholinergic muscarinic
      receptors.
AB  - The activation of phospholipase C (PLC) was examined in membranes of rat cerebral
      cortex simultaneously exposed to monoaminergic receptor and muscarinic receptor
      agonists after the treatment of membranes with two alkylating agents, N
      ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (100 microM EEDQ) and
      propylbenzilylcholine (10 nM PrBCM). Treatment of membranes with PrBCM results in
      a selective inactivation of M3 muscarinic receptors, while treatment with EEDQ
      results in a relative sparing of M1 muscarinic receptors. Stimulation of PLC by
      GTP gamma S alone in rat cortical membranes had an apparent EC50 of about 0.4
      microM, but in the presence of carbachol (1 mM) was 0.09 microM. Treatment of rat
      cortical membranes with EEDQ or PrBCM did not modify the concentration-response
      curves for GTP gamma S alone, but the ability of carbachol (1 mM) to shift the
      EC50 of GTP gamma S was lost in PrBCM-treated membranes. We have previously shown
      that dopamine, working through D1-like dopamine receptors, alters the PLC
      response to carbachol by preventing this shift in the apparent EC50 for GTP gamma
      S16. When we reproduced these experiments in EEDQ- and PrBCM-treated membranes,
      only in EEDQ-treated membranes was dopamine able to inhibit the PLC response to
      carbachol. The results indicate that the post-receptor mechanisms of PLC
      activation are distinct for the putative M1 as opposed to M3 muscarinic receptors
      in rat cortical membranes. Further, there appears to be a specific interaction
      between D1 and M3 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255173
TI  - Metrazole induction of c-fos and proenkephalin gene expression in the rat adrenal
      and hippocampus: pharmacological characterization.
AB  - We have previously reported that the administration of metrazole (MTZ) produces a
      sequential, dose-dependent induction of c-fos and proenkephalin (Penk) gene
      expression in the rat hippocampus and adrenal. The adrenal is more sensitive to
      induction of these genes by MTZ. In the present study, we have compared the
      induction of c-fos and Penk in the hippocampus and adrenal, and examined the
      consequences of selected pharmacological manipulations. Treatment with LY274614,
      a competitive NMDA-receptor antagonist, blocked MTZ-induced convulsions and the
      MTZ-induction of c-fos and PPenk mRNAs in the hippocampus, and PPenk mRNA in the
      adrenal. However, in the adrenal the MTZ-induction of c-fos was only partially
      inhibited by LY274614. A combination of peripheral acting cholinergic antagonists
      (chlorisondamine plus methylatropine) prevented the MTZ-induction of adrenal c
      fos and PPenk mRNA without significant alterations in the MTZ-induction of
      hippocampal c-fos mRNA or convulsions. Trifluoperazine, a calcium/calmodulin
      inhibitor, attenuated the MTZ-induction of c-fos mRNA while potentiating the MTZ
      induction of PPenk mRNA in both the hippocampus and the adrenal. These results
      demonstrate that the MTZ induction of c-fos and Penk gene expression in the rat
      adrenal can be modulated by drugs acting in the CNS at NMDA receptors, in the
      periphery at postsynaptic cholinergic receptors and intracellularly at the
      calcium/calmodulin signal transduction pathway. Furthermore, we provide
      additional evidence that MTZ-induction of c-fos and Penk mRNAs can be dissociated
      by drugs acting at these sites.

PMID- 8255174
TI  - Comparison of alpha-tubulin mRNA and heat shock protein-70 mRNA in gerbil brain
      following 10 min of ischemia.
AB  - In situ hybridization and Northern blot analysis were used to characterize the
      mRNA expression of alpha-tubulin, a neuroprotein crucial for neuronal structural
      and functional restoration, in comparison to that of the stress inducible heat
      shock protein-70 (HSP-70), in the same gerbil brain following 10 min of forebrain
      ischemia. The HSP-70 expression was noted in the dentate granule layer 1 h
      postischemia (PI) and became prominent in all pyramidal cell fields of the
      hippocampus in addition to the dentate layer at 6 h PI. The induction of HSP-70
      persisted in CA1 and CA2 regions and partly in dentate gyrus for up to the 1 day
      PI period examined. There was no significant HSP-70 expression in any of the
      regions of the nonischemic or 15 min PI brain. alpha-Tubulin, on the other hand,
      was expressed in all pyramidal fields of the hippocampus as well as dentate gyrus
      in nonischemic controls. A decline was noted in the CA1 region 1 h PI onward and
      was maximal at 6 h PI. Its expression, however, increased at 24 h PI (significant
      only in comparison to 15 min and 6 h PI but not to control) when it became rather
      strong in the dentate gyrus. Thus, the temporal pattern of expression of alpha
      tubulin sharply contrasted with that of HSP-70 in the PI brain as it declined in
      the vulnerable CA1 region during the 1st 24 h PI, i.e., the period when HSP-70
      was induced and its expression was lowest in the 6 h group when HSP-70 peaked. It
      was maximum in the dentate gyrus at 24 h PI when HSP-70 was marginally detectable
      in that region. These studies indicate that in early recirculation period
      following prolonged ischemia, HSP-70 mRNA is expressed in both vulnerable regions
      as well as in regions of the brain that are destined to survive while alpha
      tubulin is diminished in vulnerable regions. These data suggest a positive
      correlation between the loss of alpha-tubulin mRNA and delayed neuronal necrosis
      that follows in the vulnerable CA1 region.

PMID- 8255175
TI  - NF-kappa B-like factors in the murine brain. Developmentally-regulated and tissue
      specific expression.
AB  - NF-kappa B and related factors are important transducers of external signals to
      the cell nucleus. They are abundant in the brain, where they may be significant
      for the regulation of gene transcription in plasticity-related processes for
      instance, via activation of protein kinase C. The subunit composition and levels
      of these factors in the mouse and rat brain and other tissues, using an assay
      based on gel retardation of the oligonucleotides corresponding to the kappa B DNA
      element, are reported here. Three major kappa B-binding factors were observed.
      Factors I and II were activated by the dissociating agent deoxycholate. DNA
      protein cross-linking and antibody neutralization experiments suggest that factor
      I is a heterodimer of c-Rel and p65; factor II is a heterodimer of p50 and p65
      (authentic NF-kappa B), and of p50 and c-Rel; factor III is the p50 homodimer
      (KBF1). All three factors were generally expressed in the 17-day-old rat embryo
      and 5-day-old pup, whereas in the adult rat, expression was more limited and
      showed certain tissue specificity. Factor II was the most generally expressed and
      the only factor observed in adult brain. Factor I was only detected in the adult
      testis whereas factor III was observed in the adult spleen and, in small amounts,
      in the liver and lung. Two minor kappa B-specific factors (A and B), distinctive
      to the brain and spleen, respectively, showed very slow gel mobility. Their
      estimated molecular weights were about 125 kDa and 95 kDa, respectively.
      Expression of factor A was stable in the rat brain during development. Factor A
      may be identical to a previously described brain-specific factor, BETA (Korner et
      al., Neuron, 3 (1989) 563-572). Thus, the expression pattern of kappa B-binding
      activities is apparently developmentally regulated and tissue-specific
      particularly in the adult. In the adult mouse and rat brain, only factors II
      (probably NF-kappa B and p50/c-Rel heterodimer) and A (probably BETA) could be
      observed.

PMID- 8255176
TI  - Brief exposure to a novel environment enhances binding of hippocampal
      transcription factors to their DNA recognition elements.
AB  - The behavioral regulation of transcription factor function in hippocampus, a
      brain region activated by novelty and important for information storage, has not
      been previously studied. Sixty min after a 4 min exploration of a novel space by
      adult albino rats, electrophoretic mobility shift assays revealed a selective
      increase in specific binding to particular consensus recognition elements. For
      both AP-1 and CRE, an upper and lower band were observed in the electrophoretic
      mobility shift assay. The upper band showed increased binding restricted to the
      60 min time point after exploration; no increase was observed 30 min or less, or
      120 min or more after the novel experience. Increased binding to the lower of
      either AP-1 or CREB was observed at 30 and 120 min. When the time of exploration
      was increased from 4 to 15 min, no alterations in either the upper or lower band
      were observed in the transcription factor binding to either the AP-1 or the CRE
      element. Since the animals ceased to explore the environment after 10 min, the
      lack of binding may reflect behavioral habituation, leading to transcription
      factor deactivation. We conclude that brief, naturalistic stimulation can
      activate brain transcription factors in a time-delimited fashion, suggesting post
      translational control of protein-DNA binding. We propose that promoter elements
      of target genes critically involved in the storage of information are turned on
      by environmentally-activated transcription factors.

PMID- 8255177
TI  - In situ hybridization study of interleukin-1 beta mRNA induced by kainic acid in
      the rat brain.
AB  - The distribution patterns of interleukin-1 beta (IL-1 beta) mRNA in various brain
      regions of saline- and kainic acid-treated rats were examined using in situ
      hybridization technique. In normal rat brain, the signals of IL-1 beta mRNA were
      observed in the cerebellar Purkinje cells and in dispersed cells in the
      hypothalamus. In the case of the kainic acid treatment, IL-1 beta mRNA was
      intensely induced in the olfactory bulb, lateral septum, thalamus, hypothalamus,
      polymorphic layers of hippocampus, piriform cortex, amygdala, entorhinal cortex
      and cerebral cortex at 2 h after the injection of kainic acid. In the
      hypothalamic region, we observed the induction of IL-1 beta mRNA around the
      paraventricular hypothalamic nucleus, anterior hypothalamic area, dorsomedial and
      ventromedial hypothalamic nucleus, mammillary regions and arcuate nucleus. The
      signal of IL-1 beta mRNA was still expressed 4 h after treatment with kainic
      acid, less intensely than at 2 h, but above the control level. In these regions,
      IL-1 beta mRNA was expressed mainly in the glial cells, which were densely
      stained by Cresyl violet and did not contain glial fibrillary acidic protein.
      These results suggest that IL-1 beta is produced by a certain type of glial
      cells, maybe microglia, and might have regulatory functions in the central
      nervous system.

PMID- 8255178
TI  - Acute nicotine injections induce c-fos mostly in non-dopaminergic neurons of the
      midbrain of the rat.
AB  - Induction of c-fos gene is an immediate and early response in the cascade of
      molecular events that ultimately lead to long-term alterations in gene expression
      in neurons. The psychomotor stimulant and positive reinforcing effects of
      nicotine have been speculated to be mediated by the dopaminergic neurons of the
      ventral tegmental area (VTA). To identify the precise subsets of VTA neurons of
      the rat that mediate the acute nicotinergic effects, the pattern of expression of
      c-fos gene was mapped using immunocytochemical methods. Acute nicotine injections
      resulted in prominent Fos-like immunoreactivity (-LI) in the medial terminal
      nucleus of the accessory optic system, the interpeduncular nucleus, and in the
      caudal linear subnucleus of VTA. The neurons of other VTA subnuclei, viz., the
      rostral linear, paranigralis, nucleus parabrachialis pigmentosus, and nucleus
      interfascicularis or the substantia nigra pars compacta did not contain any cells
      with Fos-LI. Mecamylamine abolished Fos-LI in most of the VTA neurons. These
      results suggest that acute nicotine injections induce c-fos expression mostly in
      non-dopaminergic neurons of the ventral tegmental area of the rat and that
      nicotine induces c-fos most intensely in the interpeduncular nucleus, the
      superior colliculus, and several other subnuclei of the accessory optic system.

PMID- 8255179
TI  - Phosphorylation of rat brain nicotinic acetylcholine receptor by cAMP-dependent
      protein kinase in vitro.
AB  - The participation of protein kinases in phosphorylation of nicotinic
      acetylcholine receptor (nAChR) in electric organ and muscle has been precisely
      investigated in vitro and in vivo whereas phosphorylation of neuronal nAChR is
      not yet fully characterized. Here, we first report the in vitro phosphorylation
      of brain nAChR. nAChR purified from rat brains was phosphorylated in vitro by
      cAMP-dependent protein kinase (PKA), immunoprecipitated with monoclonal antibody
      against the receptor, and subjected to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) followed by autoradiography. PKA specifically
      phosphorylated nAChR on the alpha 4 subunits, and H8, an inhibitor of PKA,
      inhibited completely the phosphorylation. Under the conditions used, a maximal
      stoichiometry of the phosphorylation by PKA was near to 1 mol of phosphate/mol of
      the alpha 4 subunits. The 32P-labeled subunits were digested with S. aureas V8
      protease followed by SDS-PAGE autoradiography and the resultant phosphopeptide
      maps revealed three distinct phosphopeptide bands, one major band and two minor
      bands. Phosphoamino acid analysis of the 32P-labeled alpha 4 subunits showed that
      serine residues were exclusively phosphorylated. Based on these results,
      participation of PKA in the regulation of neuronal nAChR is discussed.

PMID- 8255180
TI  - Regional distribution in the rat central nervous system of a mRNA encoding a
      portion of the cardiac sodium/calcium exchanger isolated from cerebellar granule
      neurons.
AB  - The cardiac Na+/Ca2+ exchanger is a bidirectional electrogenic ion transporter
      that exchanges three Na+ ions for each Ca2+ ion and plays a critical role in
      returning sarcolemma Ca2+ concentrations to their resting levels. Because of the
      importance that the Na+/Ca2+ exchanger may play in maintaining neuronal Ca2+
      homeostasis in the central nervous system, we subcloned a 456 bp portion of the
      Na+/Ca2+ exchanger cDNA from RNA isolated from primary cultures of rat cerebellar
      granule neurons using the polymerase chain reaction (PCR). This cDNA fragment was
      sequenced and shown to share 91.4% sequence identity with the human and 88%
      sequence identity with the canine cardiac Na+/Ca2+ exchangers. The PCR
      amplification product was used to analyze the distribution of this portion of the
      Na+/Ca2+ exchanger mRNA in various regions of the CNS by both Northern blotting
      and in situ hybridization histochemistry. The Northern analysis showed that the
      rank order of abundance of this mRNA was: hippocampus > cortex > cerebellum >
      hypothalamus > midbrain > striatum. The in situ hybridization data indicated that
      the corresponding mRNA containing this portion of the exchanger was present in
      numerous brain regions including multiple cortical layers, the hippocampus,
      septal nuclei, various thalamic nuclei, cerebellum, hypothalamus, olfactory bulb,
      brainstem, in various regions of the thoracic spinal cord and to a lesser extent
      in the striatum. The differential distribution of the mRNA as revealed by the in
      situ hybridization pattern suggests that either additional molecular variants
      exist or that different Na+/Ca2+ exchange mechanisms may be operative in those
      cell types that contain low amounts of this fragment of the exchanger mRNA.

PMID- 8255181
TI  - Differential expression of mRNAs encoding gamma and delta subunits of
      Ca2+/calmodulin-dependent protein kinase type II (CaM kinase II) in the mature
      and postnatally developing rat brain.
AB  - The expression of mRNAs encoding gamma and delta subunits of Ca2+/calmodulin
      dependent protein kinase type II (CaM kinase II) in the brain of mature and
      postnatally developing rats was examined by in situ hybridization histochemistry.
      At the adult stage, mRNAs for both subunits were expressed in the olfactory bulb,
      and piriform cortex. The cerebral neocortex expressed the gamma subunit mRNA
      evenly through the layers II to VI at a moderate level, whereas the delta subunit
      mRNA was expressed in a distinctly laminar distribution. The hippocampal
      pyramidal and dentate granule cells expressed the gamma subunit mRNA intensely
      without any significant expression signals for the delta subunit. In the
      cerebellum, moderate expression signals for the gamma subunit were confined to
      the Purkinje cell layer, while intense expression signals for the delta subunit
      were detected in the cerebellar granule cell layer, without any significant
      expression signals in the Purkinje cell layer. In the spinal cord, mRNA for the
      gamma subunit was expressed in neurons throughout the gray matter, while the
      expression of mRNA for the delta subunit was confined to neurons in laminae I and
      IX. The expression pattern of genes for both subunits was basically accomplished
      at birth with lower intensity, except for the striatum and cerebellar Purkinje
      cells, which transiently expressed mRNA for the gamma and delta subunits,
      respectively, at birth. These results indicate that the expression of genes for
      each of the subunits of CaM kinase II is differentially regulated in various
      brain regions and that the individual subunits are involved in differential
      functions in mature and developing rat brain.

PMID- 8255182
TI  - A splice variant of the N-methyl-D-aspartate (NMDAR1) receptor.
AB  - A splice variant of the NMDA receptor (NMDAR1) was discovered containing a
      deletion of 37 amino acids near the carboxyl tail and has been designated
      NMDAR1b. The 111 nucleotides corresponding to the deleted amino acid sequence
      were found in a separate exon bounded by consensus intron/exon junction sequences
      in rat genomic DNA. A partial restriction map of genomic DNA bounding this region
      placed the deleted exon approximately 600 base pairs (bp) downstream of the
      upstream exon. RT/PCR analysis of RNA from different brain regions showed that
      the deletion variant is more abundantly expressed in the brain stem and
      cerebellum while the full-length form is expressed more abundantly in the
      olfactory bulb, striatum, hippocampus, and cortex. Northern analysis of poly(A)+
      RNA from different brain regions with probes specific for the deleted exon (i.e.,
      full-length form) and for the splice junction (deletion form) indicated
      approximately 4.4 kb transcripts. The probe for the deleted exon hybridized to
      transcripts in olfactory bulb, cortex, striatum, and hippocampus while the splice
      junction probe hybridized most strongly to transcripts in cerebellum. The results
      suggest an interesting rostral to caudal shift in the expression of splice
      variants of the NMDAR1 which may signify important functional differences in
      native forms of NMDA receptors.

PMID- 8255183
TI  - Morphine amplifies norepinephrine (NE)-induced LH release but blocks NE
      stimulated increases in LHRH mRNA levels: comparison of responses obtained in
      ovariectomized, estrogen-treated normal and androgen-sterilized rats.
AB  - In these studies we examined the temporal effects of intracerebroventricular
      (i.c.v.) infusions of norepinephrine (NE) on plasma LH and on LHRH mRNA levels in
      the organum vasculosum of the lamina terminalis (OVLT) and in neurons located in
      the rostral (r), middle (m) and caudal (c) preoptic areas (POA) of
      ovariectomized, estrogen-treated rats. Thereafter, we compared these responses to
      those which occur in androgen-sterilized rats (ASR). NE infusions not only
      increased plasma LH concentrations but within 1 h after NE, LHRH mRNA levels also
      were increased significantly in the OVLT and rPOA but not in the mPOA or cPOA. By
      4 h, these message levels still were elevated in the OVLT and rPOA and they now
      also were significantly higher than control values in the mPOA and cPOA. While NE
      also increased LH secretion in ASR, the plasma LH concentrations obtained were
      markedly blunted compared to control values. Moreover, NE infusions did not alter
      single cell levels of LHRH mRNA in any region of the rostral hypothalamus.
      Previously, we have reported that morphine (s.c.) markedly amplifies NE-induced
      LH release and questioned whether these responses are accompanied by concomitant
      augmented increases in LHRH mRNA levels. Morphine alone did not affect basal LHRH
      mRNA or plasma LH levels. However, when rats were pretreated with morphine (-15
      min) and NE was infused i.c.v. at 0 time, significant amplification of LH release
      occurred but, unexpectedly, morphine completely blocked NE-induced increases in
      LHRH mRNA levels in all of the neurons we examined. Morphine also amplified LH
      release in ASR but these responses were significantly less than those obtained in
      control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255184
TI  - Circulating gonadal steroid hormones regulate estrogen receptor mRNA in the male
      rat forebrain.
AB  - In male rats, the conversion of testosterone to estrogen via aromatization is a
      critical step in a number of androgen-mediated functions, especially reproductive
      behavior. Within the central nervous system (CNS), locally formed estrogen binds
      to its cognate estrogen receptor protein. Little is known about what factors
      regulate the expression of estrogen receptors in the male rat CNS. This study
      examined whether circulating male gonadal steroid hormones have a role in the
      regulation of estrogen receptor mRNA in brain regions critical for the expression
      of male reproductive behavior. Male rats were gonadectomized or sham operated,
      and 3 days later were sacrificed. Their brains were fixed by perfusion, frozen,
      and sectioned. Tissue sections were hybridized to an 35S-labeled 850 base cDNA
      probe, complementary primarily to the steroid binding domain of the estrogen
      receptor mRNA. Following post-hybridization washes, slides were dipped in
      photographic emulsion and exposed for 2 weeks. Estrogen receptor mRNA-containing
      neurons were observed in all brain regions previously shown by steroid hormone
      autoradiography to concentrate estrogen. Gonadectomy did not alter the number of
      estrogen receptor mRNA-producing neurons, but did produce a two-fold increase in
      the relative amount of estrogen receptor mRNA per cell in the medial preoptic
      nucleus, periventricular preoptic area, and bed nucleus of the stria terminalis.
      This study shows that circulating gonadal steroids down-regulate steady state
      levels of estrogen receptor mRNA within specific brain regions, and thereby have
      the potential to regulate the sensitivity of particular target regions in the CNS
      to estrogen.

PMID- 8255185
TI  - Expression of the rat calmodulin gene II in the central nervous system: a 294
      base promoter and 68-base leader segment mediates neuron-specific gene expression
      in transgenic mice.
AB  - Deletion analysis of the rat CaMII promoter demonstrated that the segment from 
      294 to +68 bases of CaMII was efficient as a promoter in NIH3T3 by transient
      assay. We developed transgenic mice carrying a fusion gene of this promoter
      segment and a beta-galactosidase reporter gene. This short CaMII promoter
      mediated the transgene expression in pyramidal cells of the cerebral neocortex,
      the pyriformcortex and the hippocampal regions CA1 to CA3, in granule cells of
      the dentate gyrus, in Purkinje cells of the cerebellum, and in neurons of the
      lateral vestibular nucleus of pons and the spinal cord of adult transgenic mice.
      The expression of endogenous CaMII was precisely analyzed by in situ
      hybridization in the nervous tissues. The localization of transgene expression
      was consistent with those of the endogenous CaMII in the adult transgenic mice.
      In the embryos at 13.5-15.5 days of gestation, the transgene was expressed in
      various neurons similarly to the endogenous CaMII but certain subtle differences
      were observed in the localization of expression. This short promoter of rat CaMII
      carried two sequence stretches highly conserved in the mouse, dog, chicken and
      Xenopus CaMII promoters. These conserved stretches may be involved in the
      observed neuron-specific expression of rat CaMII gene.

PMID- 8255186
TI  - Brain transcription factor expression: effects of acute and chronic amphetamine
      and injection stress.
AB  - Amphetamine influences behaviors and the expression of transcription factor genes
      in the central nervous system (CNS). A single d-amphetamine dose (7.5 mg/kg,
      i.p.) enhances behavioral stereotypy and augments brain expression of c-fos, fos
      B, fra-1, zif268, jun-B, and c-jun by 2-11 fold. When the single amphetamine dose
      is preceded by 28 saline injections over 14 days, it is half as effective in
      enhancing expression of these genes. Rats injected with 7.5 mg/kg i.p. twice
      daily for 2 weeks and sacrificed after the last injection reveal further
      attenuation or abolition of the amphetamine-induced mRNA upregulation. These
      stigmata of 'tolerance' in gene expression display partial overlap with
      behavioral tolerance, manifest as changes in locomotor activity. Rats receiving
      low (2 mg/kg) amphetamine challenge doses following the 2-week 7.5 mg/kg b.i.d.
      amphetamine treatment show tolerance to the locomotor activating effects of the
      drug; no tolerance is evident following a high (7.5 mg/kg) challenge dose. These
      data suggest that amphetamine-induced alterations in brain transcription factor
      gene expression can display 'tolerance' and possibly 'cross-tolerance' with the
      stress caused by i.p. injection.

PMID- 8255187
TI  - Functional MRI of the brain. A report on the SMRM/SMRI Workshop held in
      Arlington, Virginia. June 17-19, 1993.

PMID- 8255188
TI  - Fast proton spectroscopic imaging of human brain using multiple spin-echoes.
AB  - We introduce a multi-echo multi-slice MR proton spectroscopic imaging method,
      which allows for a dramatic reduction of the measurement time by acquiring
      multiple spin-echoes within a single repetition time. In the multi-echo multi
      slice experiment discussed in this paper, a threefold reduction in measurement
      time is obtained by sacrificing some spectral resolution. Signal-to-noise ratio
      and spatial resolution are preserved. Metabolite images of N-acetyl aspartate,
      and total choline+total creatine from multiple slices through the human brain are
      presented and compared with images obtained with a conventional single-echo multi
      slice method.

PMID- 8255189
TI  - Dynamic 13C-1H nuclear polarization of lipid methylene resonances applied to
      broadband proton-decoupled in vivo 13C MR spectroscopy of human breast and calf
      tissue.
AB  - Dynamic nuclear polarization of the coupled 13C-1H spin system was studied for
      optimizing the signal-to-noise ratio of in vivo 13C MR spectra. In particular,
      the truncated driven and transient nuclear Overhauser effect (NOE) of the proton
      decoupled 13C resonances from methylene carbons in vegetable oil and in human
      calf tissue was observed. Maximum in vivo NOE enhancements eta = 1.5 and 0.9 were
      found, respectively. Theoretical fits to the data yield 13C-1H cross-relaxation
      times in the order of 0.6 s. Significant signal enhancement over the whole in
      vivo 13C chemical shift range is obtained with minimum expense utilizing the NOE
      of the dipolar coupled 13C-1H spin system in addition to proton-decoupling. NOE
      enhanced proton-decoupled in vivo 13C MR spectra were acquired within 17 min in
      volunteer examinations from the human breast and the calf. These spectra show
      well-resolved resonances of carbons in lipids and several other cellular
      compounds.

PMID- 8255190
TI  - Development of the human brain: in vivo quantification of metabolite and water
      content with proton magnetic resonance spectroscopy.
AB  - Cerebral metabolite concentrations and water content were measured by means of
      localized proton magnetic resonance spectroscopy in 50 children, while metabolite
      peak ratios in short echo time spectra were evaluated in 173 examinations.
      Normative curves for normal development were established for two cerebral
      locations. The current report presents the first study of absolute metabolite
      concentrations and T1- and T2- relaxation as a function of age. Myo-inositol was
      found dominating the spectra at birth (12 mmoles/kg), while choline is
      responsible for the strongest peak in older infants (2.5 mmoles/kg). Creatine and
      N-acetyl groups are at significantly lower concentrations in the neonate than in
      the adult (Cr: 6, NA: 5 mmoles/kg). NA and Cr are determined by gestational age,
      whereas the concentration of ml correlates best with postnatal age. Quantitative
      1H MRS is expected to be of particular value in diagnosis and monitoring of
      pathology in infants, since metabolite ratios are often misleading.

PMID- 8255191
TI  - Generalized K-space analysis and correction of motion effects in MR imaging.
AB  - A new approach to understanding and reducing motion artifacts in magnetic
      resonance imaging (MRI) is introduced. This paper presents a novel technique for
      correcting generalized motion artifacts arising from translation, rotation,
      dilation, and compression, or any combination thereof. We also describe a new
      pulse sequence and a specialized postprocessing technique required to suppress
      these motion artifacts. The correction algorithm corrects for generalized motion.
      The theoretical basis of the correction scheme is founded upon the (k,t)-space
      formalism and the concept of pulse sequence contrast mapping functions. The
      proposed (k,t) formalism is based on the Fourier projection slice theorem and
      allows us to determine how motion artifacts arise. The correction technique
      currently suffers from some spatial resolution and signal-to-noise ratio
      limitations, and works better for small objects than large objects. These
      problems will be investigated in subsequent studies.

PMID- 8255192
TI  - Time of flight quantification of coronary flow with echo-planar MRI.
AB  - Detection and quantification of flow of the left anterior descending (LAD)
      coronary artery in healthy volunteers are demonstrated using echo-planar imaging
      (EPI). A time-of-flight (TOF) model was used to derive coronary flow velocities
      from wash-in curves, free of cardiac wall motion contamination. Short-axis
      cardiac studies were performed using a gated, gradient echo EPI technique to
      limit the effect of cardiac wall motion on coronary vessel imaging. A series of
      10 to 20 single or multislice images were acquired within a single breath-hold.
      Real-time cine series showed the LAD coronary artery with a detectability of 91%
      (n = 23) and revealed beat-to-beat variability in vessel position of a magnitude
      equal to or greater than its diameter. Flow velocity was measured in the proximal
      portion of the artery at rest and during exercise. The data demonstrated the
      known phasic pattern of LAD flow: Vsystole < or = 5 cm/s and peak Vdiastole = 14
      +/- 3 cm/s (n = 11, V = mean laminar flow velocity). During isometric exercise, a
      LAD flow velocity increase (52 +/- 24%) was detected in eight of nine subjects.
      The capacity of the EPI TOF method to detect flow velocity changes should prove
      clinically useful for future assessment of coronary flow reserve.

PMID- 8255193
TI  - Quantitative proton spectroscopy and histology of a canine brain tumor model.
AB  - Quantitative, single voxel proton nuclear magnetic resonance (NMR) spectroscopy
      and histological analysis was performed in eight dogs implanted with the
      transplantable canine glioma model of Wodinsky (Proc. Am. Assoc. Cancer Res. 10,
      99 (1969)). Signals from choline, creatine, N-Acetyl Aspartate (NAA) and lactate
      were converted to molar concentration units and correlated with the quantitative
      analysis of histologically determined tissue types within the localized volume
      selected for NMR spectroscopy. In general, compared with normal brain, the
      lesions were associated with reductions in all metabolite concentrations, with
      the exception of lactate, which was increased. NAA and creatine decreases were
      most significantly correlated with the total lesion volume (P < 0.01), suggesting
      that these compounds are present in normal brain only. Changes in choline levels
      did not correlate strongly with any particular tissue type. Lactate was found to
      increase with increasing total lesion volume (P < 0.01), but not with increasing
      percent tumor, suggesting that it accumulates in abnormal tissue other than the
      tumor. The spectra reported were similar to those observed in human
      glioblastomas, with the exception that elevations of choline were not observed.
      The transplantable canine gliosarcoma system appears to be a suitable tumor model
      for evaluation by clinical radiological techniques such as magnetic resonance
      imaging (MRI) and proton NMR spectroscopy.

PMID- 8255194
TI  - 23Na-NMR detects hypoxic injury in intact kidney: increases in sodium inhibited
      by DMSO and DMTU.
AB  - Hypoxic injury in the isolated perfused rat kidney (IPRK) was monitored using
      23Na-NMR in the presence or absence of 1.5 and 15 mM dimethylthiourea (DMTU) or
      15 mM dimethylsulphoxide (DMSO) before and after inducing hypoxia. Hypoxia
      induced a prompt exponential increase in total renal 23Na+, renal vascular
      resistance, and sodium excretion and decreased inulin clearance and adenine
      nucleotides and reduced glutathione concentrations. Lipid peroxide metabolites
      were unaltered. The increase in 23Na+ was significantly reduced (P < 0.001) by
      both DMTU and DMSO although hypoxic perturbations of function and biochemical
      parameters were not. Posthypoxic increases in renal 23Na+ include approximately
      10% from the intratubular compartment, but principally reflect the intracellular
      and interstitial compartments. The results demonstrate that 23Na-NMR is a
      sensitive indicator of hypoxic renal injury in intact kidney and suggest that
      DMTU and DMSO protect against hypoxic injury by a mechanism independent of free
      radical-binding.

PMID- 8255195
TI  - Analysis of saturated phosphatidylcholine in amniotic fluid by 31P NMR.
AB  - A technique using solubilization with sodium cholate to resolve 31P NMR
      resonances of phospholipid molecular species was applied to amniotic fluid
      samples from 16 subjects. Gestational ages from 25 to 40 weeks were represented,
      and two subjects were sampled sequentially. Fitting of the partially resolved 31P
      NMR signal of phosphatidylcholine (PC) generated an estimate of percent
      disaturated acyl PC (%dsPC) which correlated more highly with gestational age
      than did several other potential indices of fetal lung maturation, such as the
      ratio of PC to inorganic phosphate from the solubilized spectra, or PC to
      sphingomyelin from extract spectra. In a few cases, enzyme-catalyzed PC
      hydrolysis limited the precision, but did not appear to affect the accuracy, of
      the %dsPC estimates. Resolution of palmitoyl and oleoyl lyso-PC species was
      observed for both the 1- and 2-acyl isomers. Upfield shifts due to the presence
      of cis double bonds in the lone acyl chain of the lyso-PCs were analogous to
      those observed for the diacyl PCs.

PMID- 8255196
TI  - Differentiation of chronic lesions after stroke in stroke-prone spontaneously
      hypertensive rats using diffusion weighted MRI.
AB  - Apparent diffusion coefficients (ADCs) of tissue water were determined in chronic
      brain lesions of a rat stroke model, stroke-prone spontaneously hypertensive rats
      and compared with histology. ADCs increased in the order control < edema <
      gliosis < cyst. The differences between individual groups were statistically
      significant. The increase in ADC is thought to mainly reflect a relative increase
      in the extracellular space in brain tissue. ADC values may be a clinically useful
      parameter for tissue characterization.

PMID- 8255197
TI  - Cylindrical coils near self-resonance.
AB  - We present a model of birdcage resonator operation when the size of the resonator
      approaches a quarter wave length resulting in significant phase shifts along the
      current conducting elements. In the model resonators are treated as generalized
      transmission lines. Line termination determines whether the resonator is of the
      low pass or high pass type. The model correctly describes the dependence of
      resonant frequency on resonant mode number as well as the distribution of current
      along the length of the resonator.

PMID- 8255198
TI  - 31P NMR spectra of intact red blood cells: quantitation of UDPGlucose and
      UDPGalactose.
AB  - The combined levels of uridine diphosphogalactose (UDPGal) and uridine
      diphosphoglucose (UDPGlu) were measured directly by 31P NMR spectroscopy in
      intact fully oxygenated erythrocytes. Quantitative analysis was obtained using a
      sealed capillary of methylene diphosphonate (MDP) calibrated with standard
      solutions of UDPGlu and UDPGal of known concentration prepared in KRB/BSA. The
      combined peaks of UDPGlu and UDPGal were integrated after subtraction of the
      underlying broad component originating from membrane phospholipids. The average
      concentration of 27.16 +/- 5.18 nmole/ml or 8.08 +/- 1.36 mumole/100 g hemoglobin
      obtained for these metabolites correlated well with their total determined by
      HPLC of trichloracetic acid (TCA) extracts of the same samples.

PMID- 8255199
TI  - 31P relaxation rates to evaluate physiological events in the heart.
AB  - The present study was performed to determine whether 31P NMR relaxation times
      (T1) of adenosine triphosphate (ATP) might be used to monitor the resultant
      altered myocardial physiology produced by ischemia and possibly to explain
      mechanisms of altered physiology. To this end, pre- and postischemic T1s were
      determined in hearts perfused in the Langendorff mode, using 31P NMR inversion
      recovery methods. In hearts without any pretreatment (CON), post-ischemic ATP T1
      values were significantly decreased compared with pre-ischemic values (P < 0.05);
      Pre-isch: gamma = 0.58 +/- 0.08; alpha = 0.62 +/- 0.06; beta = 0.38 +/- 0.08;
      Post-isch: gamma = 0.33 +/- 0.05; alpha = 0.43 +/- 0.03; beta = 0.23 +/- 0.05. In
      groups pretreated with creatine (CR), cyclocreatine (CY), or superoxide dismutase
      plus catalase (SOD-CAT) before ischemia, the post-ischemic ATP T1 values were
      similar and were not significantly changed from pre-ischemic values. These
      combined data suggest that T1s of ATP might be used to monitor altered myocardial
      physiology and could provide insight into mechanisms of alteration.

PMID- 8255200
TI  - Complete elimination of the extracellular 23Na NMR signal in triple quantum
      filtered spectra of rat hearts in the presence of shift reagents.
AB  - A method is suggested whereby the shifted extracellular triple quantum filtered
      23Na signal of an isolated organ is completely eliminated. The method is based on
      the long relaxation time of the triple quantum coherence and on its fast
      evolution rate. When the carrier frequency is set on top of the intracellular
      sodium signal and the time interval between the last two pulses to (12 delta nu)
      1 (delta nu is the frequency difference between the intracellular and the
      extracellular signals), a complete elimination of the extracellular 23Na signal
      is achieved. The method is demonstrated for isolated rat hearts and the
      quantification of intracellular sodium using triple quantum filtered spectroscopy
      is discussed.

PMID- 8255201
TI  - A monitoring, feedback, and triggering system for reproducible breath-hold MR
      imaging.
AB  - A technique is described that provides improved reproducibility of breath-holding
      for MR image acquisition by monitoring the superior-inferior (S/I) position of
      the diaphragm. The method incorporates detection of the level of inspiration
      using an MR signal, rapid display to the patient of diaphragm position to enable
      breath-hold adjustment, and triggering of image data acquisition once appropriate
      position is attained. The response time of the system is short, approximately 10
      ms. Studies in six volunteers using this method demonstrate a considerable
      decrease in the S/I range of diaphragm position over 10 consecutive periods of
      suspended respiration. The mean range is 1.3 mm with the system, while it is 8.3
      mm without using it. It is expected that this method will be of assistance in
      many abdominal and cardiothoracic studies that use breath-hold techniques.

PMID- 8255202
TI  - A new T2*-weighting technique for magnetic resonance imaging.
AB  - This paper describes a method that prepares the longitudinal magnetization with
      T2* weighting for subsequent acquisition. The main advantage of our technique is
      its insensitivity to static field inhomogeneity. We have combined this approach
      with an ultrafast gradient-echo (Turbo-FLASH) sequence and conducted experiments
      on phantoms and volunteers to demonstrate its capability and utility. With such a
      technique a T2*-weighted image can be generated in less than a second. In the
      paper, the detail of the technique and experimental results are presented.

PMID- 8255203
TI  - Calculating spectral modulations of AB systems during PRESS acquisitions.

PMID- 8255204
TI  - Transparent 0 pi pulses.

PMID- 8255205
TI  - Development of an anti-idiotype monoclonal antibody mimicking the structure of
      lipopolysaccharide (LPS) inner-core determinants.
AB  - An anti-idiotype antibody has been developed which is specific for idiotypic
      determinants of a BALB/c mouse IgG3 monoclonal antibody (MAbY1-4A6) directed
      against the inner-core Kdo region of lipopolysaccharide (LPS). Armenian hamsters
      were immunized with MAbY1-4A6 and splenocytes from immunized animals fused with
      Sp2/0 myeloma cells. Eight clones secreting antibodies that bound to MAbY1-4A6,
      but not control IgG3, were identified and subcloned. Culture supernatants from
      one hybridoma, termed MAb4G2, contain monoclonal antibody that binds to the
      variable region of MAbY1-4A6 and dose-dependently inhibits binding of MAbY1-4A6
      to Re chemotype rough mutant LPS (Re-LPS). This antibody also inhibits binding of
      three additional mouse monoclonal antibodies specific for the inner-core of Re
      LPS. MAb4G2 also recognizes a significant proportion of antibodies present in
      polyclonal R-chemotype antisera generated in mice (Re-LPS) and rabbits (J5 Rc
      LPS). Mice and hamsters immunized with MAb4G2 or Re-LPS generate antibodies which
      cross-react with both immunogens. Cumulatively, these data suggest that MAb4G2
      can function as an internal image of the Kdo-specific monoclonal antibody, MAbY1
      4A6, mimicking the antigenic structure and immunogenicity of a portion of the LPS
      inner-core Kdo region.

PMID- 8255206
TI  - Antibodies directed against Haemophilus ducreyi heat shock proteins.
AB  - The response to heat shock in Haemophilus ducreyi has been investigated by
      labelling newly synthesized proteins with a pulse of 35S-methionine at a range of
      temperatures between 30-40 degrees C. Proteins were then separated by SDS-PAGE
      and analysed by autoradiography of the resultant profiles. Four heat shock
      proteins (HSP) were identified of apparent molecular weight < 14, 58.5, 74 and 78
      kDa. The three larger proteins appeared to be independently controlled and
      inducible in a range of H. ducreyi strains. The protein profiles were also probed
      by Western blot with serum from an immunized rabbit, serum from a rabbit infected
      intradermally with H. ducreyi, mouse monoclonal antibodies (MAb) and a pool of
      human sera from patients with chancroid. The rabbit sera, the human serum pool
      and MAb (BB11) reacted with epitopes on the HSP of 58.5 kDa, whereas only the
      immunized rabbit serum and another MAb (CC11) reacted with epitopes on the HSP of
      78 kDa. The HSP of 58.5 kDa appears to be immunogenic and may play a part in the
      host response to H. ducreyi and the pathogenesis of chancroid.

PMID- 8255207
TI  - A mouse model for varicella-zoster virus latency.
AB  - Following primary infection with varicella-zoster virus (VZV), the virus
      establishes a latent infection in humans. The molecular pathogenesis of VZV
      latency is not well understood, mainly due to the lack of an adequate animal
      model. We report here that we have developed a mouse model for VZV infection that
      involves corneal inoculation of mice. Although infected animals showed no signs
      of disease, most of the animals could not eliminate the virus early after
      infection. By PCR, we demonstrated that at 33 days post-infection (p.i.), viral
      DNA was still present in more than 60% of the animals (14/21). VZV DNA was most
      frequently detected in the trigeminal ganglia (7/14) followed by the brain stem
      (10/21), kidneys (4/21), spleen (3/20), liver (2/21) and brain (1/21). By in situ
      hybridization, a few cells positive for VZV mRNA were detected in the trigeminal
      ganglia, brain stem, cerebellum and spleen of a small number of the infected
      animals as late as 33 days p.i. No viral proteins were detected at the site of
      inoculation or in any other tissue by immunostaining. Our results suggest that
      VZV spreads in mice by both viraemia and axonal transport and establishes a non
      productive (latent) infection.

PMID- 8255208
TI  - Identification of a domain in Bordetella pertussis adenylyl cyclase important for
      subunit interactions and cell invasion activity.
AB  - Bordetella pertussis produces a calmodulin-stimulated adenylyl cyclase that
      invades animal cells and raises intracellular cAMP levels. The enzyme does not
      enter animal cells by receptor-mediated endocytosis, but the mechanism for
      invasion of animal cells has not been defined. We have proposed that the 177 kDa
      adenylyl cyclase is proteolyzed to a 45 kDa catalytic subunit and one or more
      polypeptides (invasive factor) that facilitate entry of the catalytic subunit
      into animal cells. In this study, we report the identification of a sequence of
      amino acids within the adenylyl cyclase catalytic subunit that is important for
      entry of the enzyme into eukaryotic cells. A synthetic peptide corresponding to
      amino acids 313-339 within the catalytic subunit was shown to inhibit invasion of
      neuroblastoma cells by the adenylyl cyclase. In addition, this peptide inhibited
      the association of the catalytic subunit with invasive factor. We propose that
      this domain is a site for interaction between the catalytic subunit and invasive
      factor.

PMID- 8255209
TI  - Viral, neuronal and immune factors which may influence herpes simplex virus (HSV)
      latency and reactivation.

PMID- 8255210
TI  - Use of incompatible plasmids to control expression of antigen by Salmonella
      typhimurium and analysis of immunogenicity in mice.
AB  - Salmonella spp. have been investigated as live vaccine vectors because they are
      heat stable and can elicit humoral, cellular, and secretory immune responses.
      However, the expression of some foreign antigens is toxic to bacterial vectors.
      We therefore studied an approach for the controlled expression of antigen in
      Salmonella typhimurium wherein the antigen is not expressed in vitro but is
      expressed in vivo. A model antigen, beta-galactosidase, was expressed from the
      trc promoter on one plasmid, while repression was achieved by Lacl expressed in
      trans from a second plasmid. The second repressor plasmid was incompatible with
      the expression plasmid encoding beta-galactosidase. Loss by segregation of the
      repressor plasmid in vitro correlated with increased expression of beta
      galactosidase. Oral inoculation of mice with salmonellae containing both plasmids
      induced serum IgG but not nasal, salivary, or biliary IgA antibody to beta
      galactosidase. Serum IgG as well as biliary IgA anti-S. typhimurium antibody, but
      not salivary or nasal IgA, were also detected. This salmonella vector system for
      the controlled expression of recombinant antigens may be of value for inducing
      systemic but not mucosal immunity to antigens that are toxic to bacterial
      vectors.

PMID- 8255211
TI  - [Lukwik Rajchman, leader in international health].
AB  - Ludwik Rajchman was a man caught up in the whirlwind of international politics.
      He suffered from the conquest of this country, Poland, by both Nazism and
      Communism yet managed to rise to eminence as a leader of the Health Organisation
      of the League of Nations and then of UNICEF.

PMID- 8255212
TI  - [Use of mathematical models for quantitative environmental health risk
      assessment].
AB  - Two groups of mathematical models used in the quantitative assessment of cancer
      risk resulting from exposure to chemical substances for identifying a dose
      response relationship are presented. They are as follows: statistical and
      stochastic models or those biologically motivated. Among statistical models, the
      logit, probit and Weibull models were considered. Among those biologically
      motivated, a one-hit model was analysed with special reference to they way from
      assumptions of the carcinogenesis theory to obtaining a dose-response curve. The
      two remaining models--multi-hit and multi-stage are discussed very briefly. An
      example of the fitting dose-response curves to experimental data is presented.

PMID- 8255213
TI  - [Determination of natural ionizing radiation exposure near copper mines in
      Poland].
AB  - The results of preliminary tests of natural ionising radiation performed in the
      area of mining plants and their surroundings have been presented. The survey
      included measurements of radon concentration and gamma-ray dose rate in free air
      at 25 locations, 40K, 226Ra and 228Th determination in 48 samples of ore, ore
      concentrate, floatation tailings, rock and soil as well as 226Ra determination in
      11 samples of mine water and river. It was found that the natural radioactivity
      of ore, rock, concentrate and tailings from mine is higher than the environmental
      background. For that reason a technologically enhanced natural radiation may
      occur at some places of mining plants and surrounding areas. Those places must
      undergo full dosimetric investigation and be under control. It was impossible to
      estimate how much the environment is contaminated by radon and water coming from
      mine. However one can say that generally the gamma ray background and radon
      concentration in free air of this region are at the level considered as a normal.

PMID- 8255214
TI  - [Effect of gamma radiation on the concentration of pyruvate and lactate in
      erythrocytes of healthy men after submaximal physical exercise].
AB  - The aim of this work was to study the effect of gamma radiation and submaximal
      physical exercise on the concentration of final products of anaerobic glycolytic
      pathway in erythrocytes of healthy men. Twenty one men aged 20-22 were examined.
      They underwent physical exercise at doses of 2 w/kg body weight for 15 min.
      Erythrocytes were taken in the rest and after physical exercise and were exposed
      to gamma radiation (500 Gy doses) from 60Co source. The concentration of pyruvate
      was estimated by Fermognost tests and the concentration of lactate by Boehringer
      Mannheim tests. The submaximal physical exercise was found to cause a
      significantly increased concentration of pyruvate and lactate in the non-radiated
      and irradiated erythrocytes. Gamma radiation at 500 Gy dose was found to increase
      concentration of pyruvate in erythrocytes (in the rest and after physical
      exercise) with simultaneous decrease of lactate concentration.

PMID- 8255215
TI  - [Evaluation of the usefulness of 2-hydroxypyrene determination in urine and other
      possible tests for determining exposure to polycyclic aromatic hydrocarbons].
AB  - Exposure to airborne polycyclic aromatic hydrocarbons (PAHs) occurring at
      production of coce and aluminium is one of the major occupational health
      problems. In workers exposed to airborne PAHs at high concentrations an increased
      incidence of lung cancer has been found. In the last decade numerous attempts
      were made to develop methods for the biological monitoring of exposure to this
      group od compounds. However, some of the methods like determination of thioethers
      in urine or urinary mutagenicity proved to be influenced to a large extent by
      cigarette smoking. Determination of 1-hydroxypyrene (1-HP) (pyrene metabolite) in
      urine seems to be a more promising approach. In a number of investigations
      relatively good correlation has been found between the concentration of pyrene
      and PAHs in the air as well as between the level of occupational exposure to
      pyrene and urinary excretion of 1-HP. The influence of cigarette smoking on the
      excretion of 1-HP in urine seems to be negligible as compared to the increase in
      1-HP excretion in urine resulting from occupational exposure. Further
      investigations on the kinetics of excretion of 1-HP in urine and the quantitative
      relationship between the concentration of PAHs in the air and excretion of 1-HP
      in urine under relatively well controlled conditions are necessary.

PMID- 8255216
TI  - [Analysis of the effect of physico-chemical factors on the stability of lead and
      mercury levels in biological. II. Biological material obtained from exposed
      individuals. Structural examinations].
AB  - In order to identify the structure of sediments produced in the stored urine of
      persons exposed to lead and mercury compounds, the technique of transmission
      electron microscopy was used. It was observed that the addition of preserving
      thiocyanate to urine containing lead may evoke changes in precipitation
      mechanisms. Sediments of chlorides, among others, ammonium chloride, contain
      lead.

PMID- 8255217
TI  - [Level of total cholesterol and triglycerides in blood of workers involved in
      production of ferromanganese alloys].
AB  - In the serum of steel mill workers exposed to manganese, iron, chromates,
      ultraviolet radiation and noise, levels of total cholesterol and triglycerides
      were determined. In workers under study only increased level of triglycerides was
      found in comparison with the control group. But in the group of smokers, the
      level of cholesterol increased in persons above the age of 40 and in persons
      working longer than 10 years.

PMID- 8255218
TI  - [Death rate in acute poisonings].
AB  - The analysis of death rate, based on data for the years 1989-1990, obtained from
      nine regional centres of clinical toxicology, is reported. A high death rate is
      observed in poisonings with toxic mushroom (Amanita phalloides), ethylene glycol,
      methyl, alcohol, pesticides, corrosive substances and metabolic compounds. As to
      pesticides the highest death rate is produced by poisonings with dipyridyl
      derivatives and organophosphorous compounds. A low death rate is observed in the
      case of poisonings with drugs.

PMID- 8255219
TI  - [Analysis of military service disability due to discopathy and spondylosis].
AB  - One hundred medical certificates issued by the Local Military Medical Commission
      and which served as a basis for discharging the military from the Polish Army
      were used for the analysis of discopathy and spondylosis observed in this group
      of population. The age of subjects, length of military service and service
      conditions were taken into consideration. It was revealed that over 30% of active
      military men had been discharged from the army due to discopathy and spondylosis.
      The largest group of the military suffering from these diseases (about 60%) was
      found in troops of the line.

PMID- 8255220
TI  - [Guidelines concerning criteria for confirming occupational diseases].
AB  - The authors shared their comments on the criteria for diagnosing occupational
      diseases operating nowadays in our country. This work has been inspired by an
      increasing number of inaccuracies observed in medical certificates sent to the
      Nofer Institute of Occupational Medicine in Lodz. It is believed that
      explanations presented in this paper will assist local sanitary inspectorates in
      taking proper decisions after receiving reports on clinical diagnoses of
      occupational diseases.

PMID- 8255221
TI  - Certification of health status and work ability of individuals with radicular
      pain syndrome.
AB  - Methods for diagnosis and determination of work ability of persons with
      radiculalgia were discussed following the literature and own experience. The
      author identified elements of neurological examinations, additional tests and
      consultations with other specialists which should best serve the purpose, and
      indicated the most common inaccuracies found in medical certificates.

PMID- 8255222
TI  - Two-dimensional nuclear magnetic resonance of paramagnetic metalloproteins.

PMID- 8255223
TI  - Calcium nuclear magnetic resonance.

PMID- 8255224
TI  - Pulsed electron nuclear multiple resonance spectroscopic methods for
      metalloproteins and metalloenzymes.

PMID- 8255225
TI  - Cadmium-113 nuclear magnetic resonance applied to metalloproteins.

PMID- 8255226
TI  - Continuous wave electron nuclear double resonance spectroscopy.

PMID- 8255227
TI  - Vanadyl(IV) electron nuclear double resonance/electron spin echo envelope
      modulation spin probes.

PMID- 8255228
TI  - Multidimensional nuclear magnetic resonance methods to probe metal environments
      in proteins.

PMID- 8255229
TI  - Electron paramagnetic resonance spectroscopy of iron complexes and iron
      containing proteins.

PMID- 8255230
TI  - Electron paramagnetic resonance spectroelectrochemical titration.

PMID- 8255231
TI  - Lanthanide shift reagents.

PMID- 8255232
TI  - Multifield saturation magnetization of metalloproteins.

PMID- 8255233
TI  - Combining Mossbauer spectroscopy with integer spin electron paramagnetic
      resonance.

PMID- 8255234
TI  - Voltammetric studies of redox-active centers in metalloproteins adsorbed on
      electrodes.

PMID- 8255235
TI  - Direct and indirect electrochemical investigations of metalloenzymes.

PMID- 8255236
TI  - Pulse radiolysis.

PMID- 8255237
TI  - Physical methods to locate metal atoms in biological systems.

PMID- 8255238
TI  - Alkali metal nuclear magnetic resonance.

PMID- 8255239
TI  - The immune response: an overview.

PMID- 8255240
TI  - Immunoprecipitation methods.

PMID- 8255241
TI  - A quantitative solid-phase binding assay for tubulin.

PMID- 8255242
TI  - Confocal immunofluorescence microscopy of microtubules in oocytes, eggs, and
      embryos of algae and amphibians.

PMID- 8255243
TI  - Immunolabeling of antigens in plant cells.

PMID- 8255244
TI  - Antigen localization in fission yeast.

PMID- 8255245
TI  - Nonfluorescent immunolocalization of antigens in mitotic sea urchin blastomeres.

PMID- 8255246
TI  - Ultrasmall gold probes: characteristics and use in immuno(cyto)chemical studies.

PMID- 8255247
TI  - Electron microscopy immunocytochemistry following cryofixation and freeze
      substitution.

PMID- 8255248
TI  - Microinjection of antibodies in the analysis of cellular architecture and
      motility.

PMID- 8255249
TI  - Immunoselection and characterization of cDNA clones.

PMID- 8255250
TI  - Making monoclonal antibodies.

PMID- 8255251
TI  - Production of polyclonal antibodies against proteins and peptides.

PMID- 8255252
TI  - Purification of mouse antibodies and Fab fragments.
AB  - Although monoclonal antibodies can have different properties, it should still be
      possible to purify any antibody to homogeneity. Often, by utilizing these
      differences, the purification procedure can be improved. All of the methods
      discussed are fairly simple and fast. With 1 week of work, over 50 mg of purified
      antibody can be realized. These methods can also yield material of sufficient
      quality for structural studies.

PMID- 8255253
TI  - Blot-affinity purification of antibodies.

PMID- 8255254
TI  - Influence of short-chain fatty acids produced by anaerobic bacteria on
      procoagulant activity produced by Escherichia coli and Bacteroides fragilis
      stimulated leucocytes: possible role in intra-abdominal abscess formation.
AB  - The effect of selected short-chain fatty acids (SCFA) produced by anaerobic
      bacteria on the production in vitro of procoagulant activity (PCA) by human
      mononuclear cells stimulated by either Escherichia coli or Bacteroides fragilis
      which are common pathogens in intra-abdominal infections was investigated. In
      particular, acetic, propionic, succinic, butyric, and isobutyric acids were
      evaluated. Acetic, butyric, and isobutyric acids were able to inhibit
      significantly the production of PCA by bacteria-stimulated mononuclear cells.
      Since the production of PCA leads to the deposition of fibrin which is considered
      critical to the establishment of intra-abdominal abscesses, the inhibitory effect
      exerted by SCFA present in the inflammatory environment might play an important
      modulating role in the development of abscesses complicating intra-abdominal
      infections.

PMID- 8255255
TI  - Certain fatty acids and steroids protect Tetrahymena from cell division stress
      caused by shaking.
AB  - Cultures of Tetrahymena are routinely shaken to ensure proper access to oxygen.
      Recent work showed that growth of dilute cultures (inocula < 10(4) cells ml-1) of
      T. pyriformis was sensitive to shaking. Addition of oleic acid (9 microM) or
      linoleic acid (140 microM) before or at the onset of shaking gave considerable
      protection to the cells. A similar effect was seen with ergosterol (25 microM)
      and to some extent with cholesterol (100 microM). Octanoic acid (20 microM),
      palmitic acid (140 microM) and palmitoleic acid (100 microM) had no effect.
      Paraquat (230 microM), which induced peroxidation of unsaturated fatty acids,
      increased the effect of shaking-induced cell division stress. Such results may be
      due to changes in the membrane composition of Tetrahymena. It has not been
      possible to demonstrate differences in the 14C-oleic acid labelling of
      phospholipids of cells with and without shaking.

PMID- 8255256
TI  - Haemagglutinating activities of oral strains of Streptococcus milleri group.
AB  - Of a total 148 strains of Streptococcus milleri group, 66 agglutinated sheep
      erythrocytes. The haemagglutinating strains were confined to serotypes g, h, i, j
      or were untypeable, and had no Lancefield group antigens (A to G and K), all of
      which have been shown to belong to Streptococcus intermedius. Cell surface
      hydrophobicity did not significantly differ even between the agglutinating and
      non-agglutinating S. intermedius strains. The haemagglutinating activity of
      strain 0813-1 (serotype i) was partially sensitive to heat (100 degrees C, 30
      min) or trypsin (1 mg/ml, 30 min) treatment, but completely lost after the heat
      and subsequent trypsin treatments. Only L-arginine, L-lysine (100 mM), mucin, and
      fetuin (1 mg/ml) partially inhibited the haemagglutination with native bacterial
      cells but completely inhibited that with heated cells, whereas none was
      inhibitory in the reaction with trypsin-treated cells. The results suggest that
      at least two haemagglutinins are involved in the agglutination of the S.
      intermedius strain and that the heat-stable but trypsin-sensitive haemagglutinin
      recognizes the receptors on the erythrocyte surface which contain L-arginine and
      L-lysine at the reactive site.

PMID- 8255257
TI  - [The International Chemical Safety Cards].
AB  - Information is given on a new form of safety data sheets for chemical substances:
      the "International Chemical Safety Cards", that were developed by the
      "International Programme on Chemical Safety" of the WHO, in cooperation with the
      Commission of the European Communities. The Cards are prepared by various
      scientific institutions and then peer-reviewed by a committee of internationally
      recognized experts. At the moment, 349 Cards are available in English. The
      Commission has also translated 78 Cards into the other eight official languages
      of the European Community. Among the aims of this undertaking, the most
      significant are: (a) the possibility of comparing risks associated with different
      substances, through the use of "standard phrases", whose meaning is given in a
      specific Guide; (b) circulation of information on chemical risks on a global
      level, particularly in those countries that are not able to make their own
      evaluations.

PMID- 8255258
TI  - Criteria for the ergonomic evaluation of work chairs.
AB  - On the basis of a critical overview of specialised ergonomics literature and of
      national and international standards on the subjects, this paper outlines the
      main ergonomic requirements and characteristics for work chairs. The main
      ergonomic requirements for work chairs are the following: SAFETY: the chair
      should not be the source or cause of accidents. Adaptability: the chair's
      dimensions and control features should be such that they meet the anthropometric
      characteristics of at least 90% of the potential users. Comfort: the chair should
      be physiologically comfortable for the user. To this end, the following are all
      important features: seat-plane and backrest contours, backrest height and
      inclination adjustability, padding and covering materials that allow the body to
      breath. Practicality: the chair, and in particular the control features, should
      be practical and easy to control use. Durability: the chair should offer good
      wear and durability of its components and controls. Suitability for the job: the
      chair should be appropriately designed for the intended type of job and working
      environment. For each of these requirements single parameters are considered and
      for each parameter specific qualitative and/or quantitative data are given in
      order to class each single item as: "not acceptable", "acceptable" or "good", as
      regards standards and regulations, anthropometric parameters and intended uses.
      Criteria are given for a concise assessment of each of the six main requirements
      and for a comprehensive assessment of the "ergonomic quality" of the work chair.

PMID- 8255259
TI  - Asbestosis mortality in Italy.
AB  - A total of 204 deaths due to asbestosis occurred in Italy in the period 1970
      1989, including 24 females; asbestosis death rates (per million) were 0.31 +/-
      0.05 among males and 0.4 +/- 0.02 among females. The rates increased a little
      when comparing 1980-89 with 1970-79. Deaths were concentrated in a limited number
      of geographical areas where an extensive industrial use of asbestos is known to
      have occurred and where there were also high rates of mortality due to primary
      pleural tumours.

PMID- 8255260
TI  - Evaluation of carcinogenic risk in friction product workers.
AB  - Mortality rates of two cohorts of asbestos friction product (FP) workers were
      studied in comparison with the population of the adjoining towns over periods of
      20 and 40 years respectively. The second cohort was subdivided into 3 subcohorts
      exposed to chrysotile asbestos (CA), vulcanization and/or polymerization vapours
      and gases (VPGV) and asbestos bakelite (AB) or asbestos rubber (AR) dusts. In the
      first cohort no deaths from lung cancer were recorded, even though the total
      tumour mortality was higher than in the general population. In the second cohort
      an excess tumour mortality was observed in the first subcohort for stomach cancer
      only. In the other two subcohorts the expected rates were higher for all the
      tumour sites. Following intraperitoneal injection of CA, AB and AR dusts,
      malignant tumours developed in 31.5% of the rats which received CA, and in about
      10% of the rats which were injected with AB and AR dusts. Also, the mean
      longevity of CA-treated animals was significantly lower than in the other two
      groups. Thus, the carcinogenic risk was real in the group of FP production
      workers with significant CA exposure only.

PMID- 8255261
TI  - [The problem of determining asbestos in bulk materials: a study of the effect of
      grinding on the diffractometric response of the chrysotile content in an asbestos
      cement sample].
AB  - To determine the asbestos content in a bulk sample by X-ray diffractometry, the
      sample must be previously comminuted until an adequate granulometry is reached.
      However, this treatment can produce a decrease in fibre crystallinity which, in
      turn, causes an attenuation of the diffractometric response of asbestos. The
      authors studied a "wet" comminution method that was tested on an asbestos-cement
      sample containing chrysotile. This procedure made it possible to limit the
      attenuation of the diffractometric response of chrysotile to reasonable values
      (about 20%). Moreover, the study of the comminution kinetics revealed a time
      interval during which both fibre granulometry and diffractometric response tend
      to reach a plateau value. In this interval, the comminution time is not a
      critical factor with respect to the diffractometric behaviour of chrysotile.
      Therefore, this interval offers favourable conditions for preparing bulk samples
      to be submitted to X-ray diffraction.

PMID- 8255262
TI  - [The risk of vibrations to the hand-arm system and cumulative trauma disorders in
      shoe manufacturing: a clinical case report].
AB  - The article reports the case of a woman working in a shoe factory who had been
      using vibrating tools for 5 years. Because of paresthesia in her left hand, in
      1989 she underwent various diagnostic trials that revealed an initial carpal
      tunnel syndrome of the left wrist and a homolateral epicondylitis. Measurement of
      the vibrations transmitted to the hand from the vibrating tool confirmed the
      probability of a high risk of exposure for the hand-arm system. Such adverse
      effects have been described by British authors as "cumulative trauma disorders"
      and were confirmed in this study. The importance of further studies aimed at
      estimating the type and degree of exposure to vibrations in shoe manufacturing
      workers is stressed.

PMID- 8255263
TI  - [The relationship between work and vision in a preventive medicine context: the
      initial guidelines for a correct ergonomic ophthalmological approach proposed by
      the Italian Group for the Study of the Relationships between Work and Vision
      (G.I.L.V.). I. The presentation].
AB  - Modern technology poses numerous and complex problems concerning the implications
      for health in the work/vision relationship. While many of the hypotheses made in
      the past about the possibility of serious eye alterations in non-industrial
      workers have not been confirmed by recent investigations, considerable attention
      is at present being addressed to the short- and long-term effects of office work,
      especially in the case of tasks requiring prolonged visual effort "at near
      point". The prevalence of asthenopia in such workers is rather high, between 40
      and 80%. The considerable specificity of the symptoms and the shortcomings in
      assessment of exposure in most of the research done so far has meant that no
      clear and unequivocal causal relationship between work involving intense visual
      effort and onset of asthenopia has been established. Nevertheless, from an
      analysis of the literature three main guidelines for a correct ergophthalmologic
      assessment can be identified: a) ophthalmologic assessments that will detect any
      transitory inefficiencies of the accommodation and convergence system; b)
      specific analysis of the technical and illumination conditions with special
      attention to the distribution of the natural and artificial light sources; c)
      quantification of airborne pollutants that have a potential irritative effect on
      the "ocular surface". Other environmental parameters that could be considered are
      electric and magnetic fields in the vicinity of VDTs and PCs and the microclimate
      of the workplace.

PMID- 8255264
TI  - [The relationship between work and vision in a preventive medicine context: the
      initial guidelines for a correct ergonomic ophthalmological approach proposed by
      the Italian Group for the Study of the Relationship between Work and Vision
      (G.I.L.V.). II. The method].
AB  - In view of the numerous problems concerning the relationship between work and
      vision, the Italian Group for the Study of Work/Vision Relationships has
      developed a document that sets out initial guidelines for environmental
      monitoring and health surveillance in ergophthalmology. Particular emphasis is
      given to fact-finding inspections and collection of subjective assessments that
      will enable the occupational health physician to identify any adverse factors in
      the working environment and assess the visual effort of the operators. The
      importance of cooperation between occupational health physicians and
      ophthalmologists in the various phases of ergophthalmological assessment is
      stressed. An analytical list is provided of the parameters that the
      ophthalmologist should measure during eye examination as well as the appropriate
      assessments that the occupational health physician should perform if an
      ophthalmological specialist is not available. Suggestions for periodic controls
      on the basis of visual effort and ophthalmological status are made. It is the
      task of the occupational health physician to establish the fitness or otherwise
      of the patients for the job, and for this the Group is preparing further
      documents.

PMID- 8255265
TI  - Are evaluations of carcinogenicity by various committees worth comparing?

PMID- 8255266
TI  - [A new proposal of the EEC Directorate for the protection of workers against the
      risks related to chemical agent exposure].

PMID- 8255267
TI  - [Bone marrow transplantation in thalassemia major. The progress and prospects
      after 10 years of clinical experience].

PMID- 8255268
TI  - Ultrasonography in congenital dysplasia and immature hip in infants.
AB  - The authors report about the possibilities to evaluate correct and early
      diagnosis by ultrasonographic technique in congenital infant hip dysplasia. The
      authors report the data concerning 4666 infant hips studied by clinical and
      ultrasonographic examinations during the years 1990-1991. The cases have been
      divided according to the age of patients into three groups in the first group,
      infants less than 1 month old in the II group, infants one to 3 month old; and in
      the III group, infants 3 month old and over. The use of subdivisions according to
      age allows higher statistical incidence of dysplasia and immature hip. The
      newborns and infants included in this study were at their I ultrasonographic
      examination, had not an instrumental diagnosis of dysplasia, and were not
      orthopaedic treatment. Treatment with different types of retractors were made in
      patients with ultrasonographic diagnosis of dysplasia or immature hip, according
      to the type of dysplasia and age of patient. It has been observed, according to
      attendance, in the I group of age an high incidence of immature hip (38.03%
      versus 13.01% in II group and 2.18% in third group) and dysplasia (2.81% versus
      0.07% in II group and 0.13% in III group of children). Ultrasonography is
      replacing conventional radiography as primary method for the diagnosis is of hip
      dysplasia and thereby, the evaluation of its treatment. The ultrasonography
      techniques, being harmless for the patient, simple to perform, non-invasive, and
      economical, make then attractive early diagnostic tools for screening infant
      congenital hip dysplasia. With early diagnosis, it is possible to begin immediate
      treatment of congenital dysplasia, resulting a quick resolution of pathological
      hip disorders. To achieve these results, it is necessary that the orthopaedic
      surgeon conducts an ultrasonographic examination.

PMID- 8255269
TI  - [The evaluation of body composition in children by anthropometry and impedance
      measurement].
AB  - Several anthropometric parameters (weight, height, thickness skinfolds, and body
      circumferences) together with the bioelectric impedance (BIA) were measured in a
      group of 407 healthy prepuberal children (205 males, mean age +/- SD: 6.8 +/- 1.6
      years; 202 females, mean age +/- SD: 6.6 +/- 1.6 years) who did not practice any
      competitive sport. The group was divided into six weight classes (underweight to
      obese 3). The average values of the anthropometric data, BIA, FM (which is
      derived from the thickness skinfolds and BIA), TBW (derived from BIA), AFA and
      AMA (both derived from the forearm circumference and triceps skinfold) were all
      evaluated in relation to sex and weight classes. The average values of all the
      measured thickness skinfolds, FM and AFA were higher in the females. When
      considering the body circumferences, only the wrist circumference showed a
      statistically significant difference between sexes, being higher in males. In
      contrast both the rates waist/hips circumferences and waist/thigh circumferences
      were higher in males. As far as the BIA and FM average values is concerned, these
      were higher in females. The average value of FM derived from measuring the
      thickness skinfolds (males = 17.65 +/- 4.89%: females = 23.81 +/- 4.72% of body
      weight) proved higher than that one derived from BIA (males = 17 +/- 9.02%;
      females = 19.27 +/- 9.18%). The analysis of anthropometric and BIA data in
      relation to the weight classes showed significant variations of the mean values,
      except the rates waist/hips circumferences and waist/thigh circumferences.
      Therefore our data seem to exclude the presence of any difference of the fat
      distribution between sexes in paediatric age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255270
TI  - [Reiter's syndrome. Apropos a pediatric case].
AB  - The authors report the case of a 13-year-old girl affected with urethritis,
      conjunctivitis, and oligoarticular arthritis. These symptoms represent the
      classical triad of Fiessinger-Leroy-Reiter's syndrome. The research for HIV was
      negative and the antigen HLA B27 was absent. The young patients has been treated
      by FANS and tetracycline. The authors reviewed the literature and analyses the
      epidemiology-cal, etiological and clinical problems of this disease.

PMID- 8255271
TI  - [The Bartter-like syndrome in 2 twins].
AB  - We present a case of two twins, admitted to our department at the age of 9 years
      and 9 months for poor stature-ponderal growth. Hematochemical tests showed
      hypokalemia, hypomagnesemia, metabolic alkalosis, renin increase, normal
      aldosterone values, hypocalciuria. Arterial pressure values were normal in both
      patients. Renal hypokalemia with metabolic alkalosis was hypothesized and
      therefore tubular functions during diuresis induced by intravenous 5% dextrose in
      water were evaluated and fractionated tubular resorption values of chlorides were
      identified. The two patients presented many characteristics typical of Bartter
      syndrome (suggestive facies, short stature, hypokalemia, metabolic alkalosis,
      renin increase, decreased chloride resorption) and of Gitelman syndrome (late
      onset, few symptoms, hypomagnesemia, hypocalciuria, normal renal concentration).
      The definition "Bartter-like syndrome" seems to be more suitable for these
      patients, since it can include all the clinical characteristics and biochemical
      anomalies observed.

PMID- 8255272
TI  - [2 cases of Langerhans-cell histiocytosis located in the mastoid].
AB  - The authors report two cases of eosinophilic granuloma (histiocytosis X) located
      on the mastoid, position more or less rare and similar to other kinds of
      pathology. The authors discuss the problems of the nosologic position of
      "histiocytosis X", the problems of etiopathology, the variety of symptoms and the
      complications. The many possibilities of therapy (surgical, radiant and
      chemotherapeutic) will be examined. At the end it's important to locate this
      pathology in a multidisciplinary management.

PMID- 8255273
TI  - [The partial parenteral nutrition of preterm infants with a body weight < 1000 g:
      the effects of an infusion of human albumin on plasma amino acid concentration].
AB  - This paper concerns with the changes of plasma amino acid (AA) concentrations of
      N. 10 ELBW infants receiving a regimen of partial parenteral nutrition including
      human serum albumin (HSA) as a protein supply. The plasma AA concentration has
      been compared with VLBW infants orally fed with human milk (HM) or human milk
      supplemented with human milk protein (HMP). As for the essential AA: in
      comparison to VLBW infants fed HM, the plasma concentration of VAL, PHE and LYS
      is significantly higher, that of THR, MET, LEU and HIS is similar, whereas that
      of ILE is significantly lower; in comparison to VLBW infants fed HMP, with the
      exception of PHE whose plasma concentration is higher, concentration of essential
      AA significantly lower; the percentage ratio between plasma concentration and
      intake is in the range of 1,4 to 3,3, except for LYS (= 0.83), indicating a good
      efficacy of the i.v. administered HSA as AA source, or a slow plasma clearance or
      a sustained flux of AA from body protein catabolism. Further researches are
      needed to investigate these aspects and the intermediate steps between i.v.
      infusion of HSA and the utilization of the component AA for body protein
      synthesis.

PMID- 8255274
TI  - [89th Annual meeting of the German Pediatrics Association. Wurzburg, 11-14
      September 1993. Abstracts].

PMID- 8255275
TI  - New-style abuse of press freedom.

PMID- 8255276
TI  - NIH acts to reduce discrimination.

PMID- 8255277
TI  - Funding problems loom for new German institutes.

PMID- 8255278
TI  - Survey shows concern about biotechnology continues to grow.

PMID- 8255279
TI  - Montagnier's AIDS report covers all angles.

PMID- 8255280
TI  - Genetics test report urges moratorium on disclosure.

PMID- 8255281
TI  - Taiwan to boost biomedical research.

PMID- 8255282
TI  - WHO plans guidelines for genetics research.

PMID- 8255283
TI  - Testing for Alzheimer's.

PMID- 8255284
TI  - Electronic publishing.

PMID- 8255285
TI  - A dose of molecular medicine.

PMID- 8255286
TI  - DNA replication. Replicator renaissance.

PMID- 8255287
TI  - Ancient DNA. Less cause for grave concern.

PMID- 8255288
TI  - Atavistic reaction centre.

PMID- 8255289
TI  - Music and spatial task performance.

PMID- 8255290
TI  - Human basophil degranulation is not triggered by very dilute antiserum against
      human IgE.
AB  - We have attempted to reproduce the findings of Benveniste and co-workers, who
      reported in 1988 that degranulation of human basophil leukocytes is triggered by
      very dilute (10(2)-10(120)) antiserum against IgE. The results were contrary to
      conventional scientific theory and were not satisfactorily explained. Following
      as closely as possible the methods of the original study, we can find no evidence
      for any periodic or polynomial change of degranulation as a function of anti-IgE
      dilution. Our results contain a source of variation for which we cannot account,
      but no aspect of the data is consistent with the previously published claims.

PMID- 8255291
TI  - Eukaryotic activators function during multiple steps of preinitiation complex
      assembly.
AB  - Eukaryotic activator proteins (activators) stimulate transcription by increasing
      assembly of the preinitiation complex. We have developed methods to quantify the
      stable assembly of general transcription factors into transcriptional complexes
      in response to activators. We show that activators function during at least two
      stages of preinitiation complex assembly: first, to recruit the general
      transcription factor TFIIB, and then at a second step, after TFIIB entry. It is
      at this second step that the TATA-box binding protein associated factors act.
      This step also seems to be critical for activators to stimulate transcription
      synergistically.

PMID- 8255292
TI  - Crystal structure of a bacterial non-haem iron hydroxylase that catalyses the
      biological oxidation of methane.
AB  - The 2.2 A crystal structure of the 251K alpha 2 beta 2 gamma 2 dimeric
      hydroxylase protein of methane monooxygenase from Methylococcus capsulatus (Bath)
      reveals the geometry of the catalytic di-iron core. The two iron atoms are
      bridged by exogenous hydroxide and acetate ligands and further coordinated by
      four glutamate residues, two histidine residues and a water molecule. The
      dinuclear iron centre lies in a hydrophobic active-site cavity for binding
      methane. An extended canyon runs between alpha beta pairs, which have many long
      alpha-helices, for possible docking of the reductase and coupling proteins
      required for catalysis.

PMID- 8255293
TI  - Localized hedgehog activity controls spatial limits of wingless transcription in
      the Drosophila embryo.
AB  - Cell patterning in the body segments of the Drosophila embryo requires activity
      of the segment polarity genes, a molecularly heterogeneous group defined by a
      generic mutant phenotype. Two of these genes, wingless (wg) and hedgehog (hh),
      encode proteins that enter the secretory pathway, implicating them as signals
      that instruct the fates of neighbouring cells. Genetic analysis has identified wg
      transcription as one of the targets of hh activity and it has been suggested that
      the spatial control of wg expression depends on the limited range of the hh
      signal and the differential competence of responding cells. I have tested this
      model by driving ubiquitous expression of the hh gene using the Hsp70 promoter.
      Here I report that, as predicted, this causes the ectopic activation of wg in
      only a subset of the cells of each parasegment. Using another target of hh
      activity as a probe, I demonstrate that the competence of cells to express wg is
      independent of their ability to receive the hh signal. Finally, I show that wg
      activation requires the function of the segment polarity gene fused, suggesting
      that the putative hh signal is transduced by the serine/threonine kinase that
      fused encodes.

PMID- 8255294
TI  - Neuronal growth cone collapse and inhibition of protein fatty acylation by nitric
      oxide.
AB  - Nitric oxide, a free-radical gas produced endogenously by several mammalian cell
      types, has been implicated as a diffusible intercellular messenger subserving use
      dependent modification of synaptic efficacy in the mature central nervous system.
      It has been suggested on theoretical grounds that nitric oxide might play an
      analogous role during the establishment of ordered connections by developing
      neurons. We report here that nitric oxide rapidly and reversibly inhibits growth
      of neurites of rat dorsal root ganglion neurons in vitro. In addition, we show
      that exposure to nitric oxide inhibits thioester-linked long-chain fatty
      acylation of neuronal proteins, possibly through a direct modification of
      substrate cysteine thiols. Our results demonstrate a potential role for nitric
      oxide in the regulation of process outgrowth and remodelling during neuronal
      development, which may be effected at least in part through modulation of dynamic
      protein fatty acylation in neuronal growth cones.

PMID- 8255295
TI  - Phosphatidylinositol transfer protein required for ATP-dependent priming of
      Ca(2+)-activated secretion.
AB  - Elucidation of the reactions responsible for the calcium-regulated fusion of
      secretory granules with the plasma membrane in secretory cells would be
      facilitated by the identification of participant proteins having known
      biochemical activities. The successful characterization of cytosolic and vesicle
      proteins that may function in calcium-regulated secretion has not yet revealed
      the molecular events underlying this process. Regulated secretion consists of
      sequential priming and triggering steps which depend on ATP and Ca2+,
      respectively, and require distinct cytosolic proteins. Characterization of
      priming-specific factors (PEP proteins) should enable the ATP-requiring reactions
      to be identified. Here we show that one of the mammalian priming factors (PEP3)
      is identical to phosphatidylinositol transfer protein (PITP). The physiological
      role of PITP was previously unknown. We also find that SEC14p, the yeast
      phosphatidylinositol transfer protein which is essential for constitutive
      secretion, can substitute for PEP3/PITP in priming. Our results indicate that a
      role for phospholipid transfer proteins is conserved in the constitutive and
      regulated secretory pathways.

PMID- 8255296
TI  - Cloning and characterization of an extracellular Ca(2+)-sensing receptor from
      bovine parathyroid.
AB  - Maintenance of a stable internal environment within complex organisms requires
      specialized cells that sense changes in the extracellular concentration of
      specific ions (such as Ca2+). Although the molecular nature of such ion sensors
      is unknown, parathyroid cells possess a cell surface Ca(2+)-sensing mechanism
      that also recognizes trivalent and polyvalent cations (such as neomycin) and
      couples by changes in phosphoinositide turnover and cytosolic Ca2+ to regulation
      of parathyroid hormone secretion. The latter restores normocalcaemia by acting on
      kidney and bone. We now report the cloning of complementary DNA encoding an
      extracellular Ca(2+)-sensing receptor from bovine parathyroid with
      pharmacological and functional properties nearly identical to those of the native
      receptor. The novel approximately 120K receptor shares limited similarity with
      the metabotropic glutamate receptors and features a large extracellular domain,
      containing clusters of acidic amino-acid residues possibly involved in calcium
      binding, coupled to a seven-membrane-spanning domain like those in the G-protein
      coupled receptor superfamily.

PMID- 8255297
TI  - Characterization of proteins that interact with the cell-cycle regulatory protein
      Ran/TC4.
AB  - The human Ras-related nuclear protein Ran/TC4 (refs 1-4) is the prototype of a
      well conserved family of GTPases that can regulate both cell-cycle progression
      and messenger RNA transport. Ran has been proposed to undergo tightly controlled
      cycles of GTP binding and hydrolysis, to operate as a GTPase switch whose GTP-
      and GDP-bound forms interact differentially with regulators and effectors. One
      known regulator, the protein RCC1 (refs 12, 13), interacts with Ran to catalyse
      guanine nucleotide exchange, and both RCC1 and Ran are components of an intrinsic
      checkpoint control that prevents the premature initiation of mitosis. To test and
      extend the GTPase-switch model, we searched for a Ran-specific GTPase-activating
      protein (GAP), and for putative effectors (proteins that interact specifically
      with Ran/TC4-GTP). We report here the identification of a Ran GAP and its use to
      characterize the GTP-hydrolysing properties of mutant Ran proteins, and the
      identification and cloning of a binding protein specific for Ran/TC4-GTP.

PMID- 8255298
TI  - Replication structure of the human beta-globin gene domain.
AB  - The animal cell genome is organized into a series of replicons with an average
      size of 50-300 kilobases; each of these units is characterized by its own origin
      of replication which serves as the point of initiation for DNA synthesis. In
      animal viruses, origin usage can be regulated by cis-acting elements, and in some
      cases, replication may be cell-type specific. Little is known, however, about the
      organization and control of endogenous tissue-specific gene replication. To
      understand this process, we have used a replication direction assay to examine
      DNA fragments covering more than 200 kilobases of the human beta-like globin
      domain, and have identified a single bidirectional origin located upstream of the
      beta-globin itself. This locus is used to initiate DNA synthesis in expressing
      cells, where the globin domain replicates early, and in non-expressing cells,
      which are characterized by late replication of the same region. Deletion of this
      origin sequence, as occurs in the haemoglobin Lepore syndrome, cancels
      bidirectional DNA synthesis at this site and leads to a striking reversal of
      replication direction upstream to the locus. This represents the first genetic
      proof of the existence of specific, discrete origins of replication in animal
      cells.

PMID- 8255299
TI  - A morphological biosensor for mammalian cells.
AB  - An electrical biosensor is described that can continuously track morphological
      changes of adherent cells providing quantitative data from both sparse and
      confluent cultures. The method is capable of detecting vertical motion of cells
      of the order of 1 nm, much below the resolution of an optical microscope.

PMID- 8255301
TI  - Special issue: Rural health in North Carolina.

PMID- 8255300
TI  - Rural health in North Carolina.

PMID- 8255302
TI  - A report from the Community Practitioner Program.

PMID- 8255304
TI  - Caring for people in eastern North Carolina.

PMID- 8255303
TI  - Extending and enhancing health care through the North Carolina Cooperative
      Extension Service.

PMID- 8255305
TI  - An injury control strategy for rural North Carolina.

PMID- 8255306
TI  - Agricultural hazards in North Carolina.

PMID- 8255307
TI  - AIDS in rural North Carolina.

PMID- 8255308
TI  - Drug compliance. Are you getting the most out of your medicine?

PMID- 8255309
TI  - When "my heart stood still".

PMID- 8255310
TI  - Infant mortality in rural North Carolina.

PMID- 8255311
TI  - Reducing the burden of chronic disease in rural North Carolina.

PMID- 8255312
TI  - Infections acquired in the great out-of-doors of North Carolina.

PMID- 8255313
TI  - Environmental conditions in rural North Carolina.

PMID- 8255314
TI  - Confronting psychiatric problems and issues in rural areas with help from primary
      care physicians.

PMID- 8255315
TI  - The reinvention of traditional medicine in western North Carolina.

PMID- 8255316
TI  - [An insidious worm: Strongyloides stercoralis].

PMID- 8255318
TI  - [Disorders of the facial nerve as a cause of facial asymmetry at birth].

PMID- 8255317
TI  - [The surgical treatment of epilepsy].

PMID- 8255319
TI  - [Cell and disease. IX. Receptor pathology].

PMID- 8255320
TI  - [Strongyloides stercoralis, an insidious oddity].

PMID- 8255321
TI  - [Results of the neurosurgical treatment of patients with drug-resistant epilepsy:
      psychosocial aspects].
AB  - OBJECTIVE: Evaluation of psychological and social functioning of patients after
      neurosurgical treatment for pharmacologically intractable epilepsy. DESIGN:
      Descriptive study. SETTING: University Hospital Utrecht in collaboration with the
      Institute for Epilepsy in Heemstede, the Netherlands. METHOD: After two years'
      follow-up, social functioning, vocational adjustment and emotional stability were
      assessed in a group of 13 adult patients treated surgically between 1985 and 1992
      for intractable seizures. RESULTS: The majority of the patients improved or at
      least maintained their social and employment status. Emotional functioning showed
      minor changes for anxiety and emotional stability. CONCLUSION: The outlook for
      improvement in psychosocial functioning for epileptic patients treated
      neurosurgically is promising. Minor changes were found in emotional stability.

PMID- 8255322
TI  - [Mild sequelae 12 years following massive aspiration of barium sulfate in the
      lungs].
AB  - A twelve-year-old girl, who as a baby underwent an investigation of the
      oesophagus and stomach with barium roentgen contrast fluid, during which there
      was massive aspiration of barium contrast into the right lung, at follow-up
      showed no abnormalities, apart from slight signs of peribronchial granulomatosis
      or fibrosis. If there is an enhanced risk of aspiration or an oesophago-tracheal
      fistula is suspected it is better to use an isotonic water-soluble contrast
      fluid.

PMID- 8255323
TI  - [Carbon monoxide poisoning as a trigger for myocardial infarction].
AB  - A male aged 70 became unwell during work on the motor of his boat. He had an
      acute myocardial infarction, complicated by arrhythmias, which had probably been
      triggered by carbon monoxide intoxication. After treatment with, among other
      things, oxygen he recovered. Although the patient had experienced mild angina
      pectoris in the past, he had been symptom-free for years without medication. It
      is therefore suggested that the carbon monoxide intoxication played an important
      part in this case.

PMID- 8255324
TI  - [Is laparoscopy of value in acute appendicitis].

PMID- 8255325
TI  - [Treatment possibilities in basal cell carcinoma].

PMID- 8255326
TI  - [Cost and effectiveness of diagnosis and treatment of patients with dyspepsia as
      determined by computer model].

PMID- 8255327
TI  - [Consequences of drug addiction of the mother for the child: current status in
      relation to knowledge and management policy in The Netherlands].

PMID- 8255328
TI  - [Pain in the upper abdomen caused by pulmonary embolism].

PMID- 8255329
TI  - [In search of a second opinion].

PMID- 8255330
TI  - [Phenylketonuria inspite of screening].

PMID- 8255331
TI  - [Dyspnea without wheezing in children with COPD].

PMID- 8255332
TI  - [Stricter examination: the final hours of the WAO? (Law for Work Disability
      Insurance)].

PMID- 8255333
TI  - [Hyperventilation: not a cause of panic attacks].

PMID- 8255334
TI  - [The significance of cluster analysis in the study of causes of leukemia in
      children].

PMID- 8255335
TI  - [Current viewpoint concerning chronic lymphatic leukemia].

PMID- 8255336
TI  - [Life insurance medicine: insurance for risk of dying].

PMID- 8255337
TI  - [Cell and disease. X. disorders in signal transduction: dysregulation of cell
      growth in cancer].

PMID- 8255338
TI  - [Hyperventilation: not a cause of panic attacks].
AB  - OBJECTIVE: To investigate the importance of hyperventilation in the pathogenesis
      of panic attacks. DESIGN: Descriptive. SETTING: The Jelgersma Outpatient Clinic
      at Oegstgeest and the University Hospital Leiden, the Netherlands. METHOD: In 57
      psychiatric patients with a panic disorder and 96 somatic patients with
      unexplained somatic complaints suggestive of hyperventilation, a Hyperventilation
      Provocation Test (HVPT) was conducted. Of the somatic patients, 33 had recently
      experienced a panic attack. During the test, various physiological and symptom
      criteria for the Hyperventilation Syndrome were assessed. Several measures for
      concomitant psychopathology were collected as well. RESULTS: No significant
      differences were found in physiological criteria for the Hyperventilation
      Syndrome between psychiatric patients with a panic disorder (PD) and somatic
      patients with (PA+) or without (PA-) a recent panic attack. On all symptom
      criteria, however, PD and PA+ patients obtained comparable scores, while both
      groups scored higher than PA- patients. On most measures for concomitant
      psychopathology, PD patients scored higher than PA+ patients, who on their part
      scored higher than PA- patients. CONCLUSION: Hyperventilation is of secondary
      importance in the pathogenesis of panic attacks and an early diagnosis of panic
      attacks or panic disorder may be conducive to more adequate treatment.

PMID- 8255339
TI  - [Marked variations in phototherapy policy for neonatal jaundice in Dutch
      centers].
AB  - OBJECTIVE: To determine what guidelines are used in Dutch hospitals in the
      management of neonatal hyperbilirubinaemia. DESIGN: Descriptive. MATERIAL AND
      METHOD: Paediatricians in 63 hospitals were sent a standard guideline diagram of
      phototherapy management and asked to describe how their management differed. The
      10 neonatal intensive care units in the Netherlands were asked to send their
      phototherapy guidelines in more detail. RESULTS: Thirty-four hospitals (54%) and
      the 10 neonatal centres (100%) responded. The data obtained showed no general
      agreement; several different guidelines were used, notably with respect to the
      serum bilirubin concentration levels and the number of postnatal hours.
      CONCLUSION: We recommend that consensus should be reached on the use of
      phototherapy. A more restricted use of phototherapy probably would save costs
      without loss of quality.

PMID- 8255340
TI  - [The clinical diagnostic value of studies using magnetic stimulation].
AB  - OBJECTIVE: To assess the clinical value of magnetic stimulation in various
      neurological disorders. DESIGN: A retrospective, descriptive study. SETTING:
      Department of Neurology and Clinical Neurophysiology, Medisch Spectrum Twente,
      Enschede. METHOD: Evaluation of motor pathways by magnetic stimulation of the
      human brain and peripheral nervous system is a new, noninvasive technique. A
      magnetic field pulse, produced by a wire coil, induces a small stimulating
      current applied to the motor cortex, cervical or lumbar spine or peripheral
      nerves. Muscle responses can be recorded by EMG recording systems in upper and
      lower extremities. Central conduction times can be obtained by computing latency
      differences between cortical and cervical or lumbar stimulation respectively.
      Magnetic motor evoked potentials were recorded in 60 patients with various
      neurological disorders, including multiple sclerosis, motor neuron disease,
      spinal and peripheral disorders. RESULTS: Abnormal motor evoked potentials were
      recorded in 5 of 8 patients with multiple sclerosis, 5 of 5 with motor neuron
      disorder, 5 of 6 with hereditary spastic paraplegia, 12 of 16 with various spinal
      disorders, 6 of 11 with lower motor neuron disorders, 0 of 4 with hysterical
      paralyses and 7 of the 10 remaining patients. However, these abnormalities were
      non-specific and could be suspected in most cases after physical examination.
      CONCLUSION: Magnetic stimulation is a painless and safe technique of which the
      clinical usefulness is still limited. It is likely that it will gain an important
      place in diagnosing neurological disorders, especially with involvement of motor
      pathways.

PMID- 8255341
TI  - [Ameboma of the large intestine and rectum].
AB  - Amoeboma was diagnosed in three patients: a Bengal seaman aged 40 and two Dutch
      citizens who had lived in the tropics, a man aged 41 and a woman aged 56. The
      first-mentioned patient had a rectal tumour easily inspected by sigmoidoscopy; a
      biopsy sample contained Entamoeba histolytica. The faeces contained no cysts. The
      two other patients had coecal amoebomas. They had been operated elsewhere on
      suspicion of appendicitis and had been treated with metronidazole, which had
      failed to eliminate the amoebae. The faeces still contained cysts. One patient
      had trophozoites in a biopsy sample. The serum of all three patients contained
      anti-amoeba antibodies. Two patients were treated successfully with a combination
      of metronidazole (a tissue amoebicide) and diloxanide (a lumenal amoebicide). In
      one patient this combination failed, and emetine had to be substituted for the
      metronidazole, also because of an allergic reaction. Amoeboma of colon or rectum
      is one of the many manifestation forms of amoebiasis, but it is rare. While in
      amoebic colitis tissue necrosis (histolysis) is encountered almost exclusively,
      in amoeboma there is a violent inflammatory reaction with formation of a
      pseudotumour by granulation tissue, possibly due to secondary bacterial
      infection. Endoscopy and determination of circulating antibodies against the
      causative agent E. histolytica have by now improved the diagnosis so much that
      adequate treatment without surgical intervention is possible in principle. As
      with so many exotic diseases, a stay in the tropics is the key to the diagnosis.

PMID- 8255342
TI  - [Peer review: the all-seeing eye].

PMID- 8255343
TI  - [Intravenously administered immunoglobulin first-choice remedy in autoimmune
      diseases?].

PMID- 8255344
TI  - [Neurological symptoms in newborn infants as a result of the use of
      psychopharmaceuticals during pregnancy].

PMID- 8255345
TI  - [Neurological symptoms in newborn infants as a result of the use of
      psychopharmaceuticals during pregnancy].

PMID- 8255346
TI  - [Home care of patients with a cerebrovascular accident].

PMID- 8255347
TI  - [10 years of chorionic villi sampling and the weighing against amniocentesis].

PMID- 8255348
TI  - Not all dementia is secondary to Alzheimer's disease.

PMID- 8255349
TI  - Public attitudes, legislation, and ethical components of organ donation.

PMID- 8255350
TI  - Choice of primary care specialties by graduates of the University of Nebraska
      Medical Center 1978-1992.

PMID- 8255351
TI  - Heart transplantation in Lincoln, Nebraska: the Nebraska Heart Transplant Program
      experience.
AB  - The results of the Nebraska Heart Transplant Program are presented. Survival at
      one and four years, cost, waiting time and return to work rates are reported and
      compared to known standards. Survival is 91 percent at one year and 76 percent at
      four years after transplant. These data as well as costs, waiting time and return
      to work compare favorably with published and reported data. We conclude the
      results of the Nebraska Heart Transplant Program by all parameters evaluated are
      excellent. Referral of patients to distant programs causes needles inconvenience
      and higher patient costs, and is not justified.

PMID- 8255352
TI  - Is morphine dependence mediated exclusively by the Mu receptor?
AB  - Regional cerebral glucose utilization (RCGU) and behavior during naloxone
      precipitated withdrawal were studied in rats made dependent on either sufentanil,
      a highly selective mu opiate agonist, or morphine. Changes in RCGU during
      withdrawal in 23 of 24 anatomically related limbic and brainstem structures were
      indistinguishable between rats dependent on morphine or sufentanil. Linear
      regression analysis indicated that RCGU changes during withdrawal in these two
      groups were highly correlated (r = 0.95). Withdrawal behaviors (autonomic signs
      of withdrawal, jumps, weight loss, and incidence of diarrhea) were likewise
      indistinguishable between the two groups. The correlations of both these
      measurements of dependence suggest that chronic occupation of mu opiate receptors
      alone is sufficient to produce dependence that is indistinguishable from morphine
      dependence.

PMID- 8255353
TI  - Effects of membrane peroxidation on [3H]acetylcholine release in rat cerebral
      cortical synaptosomes.
AB  - [3H]Acetylcholine (ACh) release, malonaldehyde formation and 45calcium-uptake
      were measured in rat cerebral cortical nerve terminal that were exposed to
      various concentrations of ferrous and ascorbate ions. At a constant molar ratio
      of 25:1, ferrous:ascorbate, these ions increased malonaldehyde (MA) synthesis in
      a concentration-dependent manner. Treatment with these ions in the same ratio
      also induced a dose-related inhibition of the K(+)-depolarization-induced release
      of newly synthesized [3H]ACh. Combined exposure to Fe2+/ascorbate also reduced
      calcium ionophore A23187-induced [3H]ACh release. Neither ferrous nor ascorbate
      ions alone altered depolarization- or ionophore-induced [3H]ACh release over this
      concentration range. Depolarization- and A23187-induced 45calcium uptake were not
      affected by peroxidation, suggesting that membrane peroxidation influenced some
      process in the release-process subsequent to calcium influx in a manner similar
      to what is observed during aging.

PMID- 8255354
TI  - Autoradiographic localization of strychnine-sensitive glycine receptor in bovine
      adrenal medulla.
AB  - The presence of an uptake system and a functional glycine receptor in adrenal
      medulla chromaffin cells was investigated using an autoradiographic technique in
      adrenal gland slices. Specific 3[H]glycine binding was observed in both adrenal
      cortex and medulla slices, while only specific binding of [3H]strychnine was seen
      only in chromaffin cells and was not associated with cortical cells. [3H]Glycine
      binding sites in the cortex are apparently different from those of [3H]strychnine
      binding sites in the medulla since excess strychnine does not displace
      [3H]glycine from adrenal cortex but does so from medulla. This difference
      supports biochemical evidence for glycine transport into medulla cells and
      glycine receptor sites on the chromaffin cell membrane.

PMID- 8255355
TI  - Characterization of [3H]vesamicol binding in rat brain preparations.
AB  - The binding of (1)-[3H]vesamicol was characterized in several subcellular
      fractions and brain regions of the rat. Binding to a lysed P2 fraction from the
      rat cerebral cortex reached equilibrium within 4 min at 37 degrees C and was
      reversible (dissociation half-time 4.9 min). At least two binding affinities were
      found in P2 fractions from the cerebral cortex (Kd: 21 nM and 980 nM), striatum
      (Kd: 28 nM and 690 nM), and cerebellum (Kd: 22 nM and 833 nM). High affinity Bmax
      values were highest in striatum (1.17 pmol/mg protein), followed by cerebellum
      (0.67 pmol/mg protein), and cerebral cortex (0.38 pmol/mg protein). Low affinity
      Bmax values were highest in cerebellum (5.2 pmol/mg protein), with similar values
      for cerebral cortex (3.7 pmol/mg protein) and striatum (3.8 pmol/mg protein).
      High affinity but not low affinity binding in each brain region was
      stereospecific. Another inhibitor of vesicular ACh-transport also displaced 1
      vesamicol binding potently (IC50: 17 nM) and efficaciously (over 90%). Both high
      affinity and low affinity Bmax values for [3H]vesamicol-binding were highest in a
      partially purified synaptic vesicle fraction, followed by purified synaptosomes,
      crude membranes and P2 fractions. Specific binding was not observed in a
      mitochondria-enriched fraction. Crude membrane preparations of primary, neuron
      enriched whole brain cultures also exhibited high (64 nM) and low affinity (1062
      nM) [3H]vesamicol binding. Isoosmotic replacement of 0.18 M KCl in the binding
      buffer with NaCl had no effect on binding. These results suggest that at least
      some high affinity [3H]vesamicol binding in rat brain preparations may be
      associated with synaptic vesicles, some of which may not be cholinergic in
      origin.

PMID- 8255356
TI  - Vesicular and carrier-mediated depolarization-induced release of [3H]GABA:
      inhibition by amiloride and verapamil.
AB  - The Ca(2+)-dependent, presumably exocytotic fraction of the [3H]GABA released by
      depolarization is dissected from the depolarization-induced Na(+)-dependent,
      carrier-mediated fraction of [3H]GABA release in mouse brain synaptosomes. GABA
      homoexchange is prevented by the [3H]GABA carrier blocker, DABA. The absence of
      external Na+ completely abolishes the release of the carrier-mediated, presumably
      cytoplasmic release of [3H]GABA induced by homoexchange and heteroexchange with
      GABA and DABA, respectively. The carrier-mediated, Na(+)-dependent fraction of
      the depolarization-induced release of [3H]GABA is resistant to tetrodotoxin (TTX)
      but is sensitive to amiloride and verapamil. The Ca(2+)-dependent fraction of the
      [3H]GABA released by high K+ depolarization is also completely abolished by
      amiloride (from 300 microM) and sensitive to verapamil (30 microM), but in
      contrast is insensitive to the absence of external Na+ and to DABA. On the basis
      of these results we conclude that amiloride and verapamil inhibit high K(+)
      induced release of [3H]GABA by antagonizing the entrance of Ca2+ (and possibly
      Na+ when external Ca2+ is absent) through a population of voltage sensitive
      presynaptic Ca2+ channels activated by depolarization.

PMID- 8255357
TI  - Fusogenic properties of Sendai virosome envelopes in rat brain preparations.
AB  - Sendai virosomes were characterized with respect to their ability to bind to,
      fuse with, and introduce substances into several rat brain preparations.
      Encapsulation efficiency for Sendai virosomes was enhanced but binding to
      cerebral cortical P2 preparations was attenuated by addition of bovine brain
      phosphatidylcholine during reconstitution. A higher percentage of Sendai
      virosomes than phosphatidylcholine liposomes appeared to bind to, fuse with and
      subsequently deliver [14C]sucrose into osmotically labile pools of the P2
      preparation. Fusogenic activity was estimated by measuring dequenching of
      fluorescently labelled N-NBD-phosphatidylethanolamine. More virosomally
      encapsulated [14C]sucrose was bound to the P2 fraction than introduced into
      osmotically labile organelles, and the fraction of vesicles undergoing fusion was
      intermediate between these two values. Non-encapsulated [14C]sucrose did not bind
      to and was not taken up by the P2 fraction in a quantifiable manner. Virosomal
      envelopes also bound to primary cultures of rat brain neurons and glia in an
      apparently saturable manner. Addition of increasing amounts of the
      adenoassociated virus-derived vector pJDT95 increased encapsulation efficiency,
      and virosomes reconstituted in the presence of 60 micrograms DNA retained most of
      their binding activity (5.4% of total label) compared to those containing
      [14C]sucrose alone (8.4%). These data indicate that Sendai virosomes may be
      useful in the delivery of substances into brain-derived tissues, potentially for
      the modulation of gene expression and neurotransmission.

PMID- 8255358
TI  - Absence of an effect of the lithium-induced increase in cyclic GMP on the cyclic
      GMP-stimulated phosphodiesterase (PDE II). Evidence for cyclic AMP-specific
      hydrolysis.
AB  - Chronic treatment of rats with LiCl is known to induce a decrease in cAMP, while
      this decrease has also been found to occur together with both a simultaneous
      increase in total cortical phosphodiesterase (PDE; EC 3.1.4.17) activity and a
      concomitant increase in cGMP. These studies have implicated an involvement of PDE
      in lithium (Li+) action and it has been suggested that cGMP and the cGMP
      stimulated PDE may be instrumental in the observed effects of Li+ on cAMP. In
      this study, three isozymes of PDE were isolated and identified from rat cortex
      and their activity determined, together with simultaneous measurement of cAMP and
      cGMP, after chronic treatment with oral LiCl (0.35% m/m). Li+ treatment exerted
      profound effects on cyclic nucleotides in the cortex, inducing significant
      suppression of cAMP while increasing cGMP levels. However, the ion only induced a
      slight but insignificant increase in the activities of the three PDE isozymes. To
      confirm these observations, methylparaben (MPB), a drug demonstrating both an
      ability to induce a selective stimulation of cAMP-specific PDE and also to lower
      intracellular levels of cGMP, was co-administration orally (0.4% m/m) with Li+
      over the same period. This combination emphasized certain actions of Li+ not
      noted with Li+ alone. MPB inhibited the Li(+)-induced increase in cGMP, yet did
      not prevent the ion from decreasing cAMP. However, the combination of Li+ and MPB
      engendered a synergistic 100% increase in the activity of the membrane-bound,
      cAMP-specific PDE, PDE IV. This combination also produced a significant
      suppression of cAMP, while no reduction in cGMP was observed.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8255359
TI  - Experimental Parkinson's disease in monkeys. Effect of ergot alkaloid derivative
      on lipid peroxidation in different brain areas.
AB  - The effects of the Parkinsonism induced by the neurotoxin 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) were evaluated in four different monkey brain
      areas (frontal and occipital cortex, caudate putamen, substantia nigra). The
      basal and stimulated lipid peroxidation and the reduced glutathione (GSH)
      concentration were evaluated in three groups of male Macaca fascicularis monkeys
      (6 animals/group): (a) controls; (b) MPTP-treated animals; (c) animals treated
      with MPTP and alpha-dihydroergocryptine (DEK; ergot alkaloid characterized by a
      dopaminergic agonist action). In MPTP-treated animals the GSH concentration was
      unchanged or decreased in a non-significant way in the frontal and occipital
      cortex, and in substantia nigra. The basal thiobabituric acid reactive substance
      (TBARS) concentrations were significantly higher in the caudate putamen and
      substantia nigra of MPTP-treated animals. In the MPTP-treated monkeys the DEK
      administration induced a restoration of basal TBARS values to nearly normal ones.
      By incubating tissue from different brain areas with FeSO4 plus ascorbic acid,
      the stimulation of lipid peroxidation decreased the TBARS production in the
      substantia nigra of the MPTP-treated animals. These results, taken together, may
      indicate that an increased lipid peroxidation could possibly play a role in
      producing the Parkinson-like syndrome by MPTP and that a free radical excess
      could be responsible for the degeneration of the substantia nigra. The treatment
      with an ergot alkaloid (i.e., alpha-dihydroergocryptine) partially antagonizes
      the MPTP-induced increase in basal TBARS concentration in caudate putamen.

PMID- 8255360
TI  - Utilization of ketone bodies by chick brain and spinal cord during embryonic and
      postnatal development.
AB  - Lipid synthesis from acetoacetate and 3-hydroxybutyrate was studied in chick
      embryo from 15 to 21 days and in chick neonate from 1 to 21 days. Embryonic
      spinal cord showed higher ability than brain to incorporate acetoacetate into
      total lipids, although a sharp decrease was found at hatching. 3-Hydroxybutyrate
      incorporation into total lipids was also higher in spinal cord than in brain,
      especially during the embryonic period. Phospholipids were the main lipids formed
      in both tissues from both precursors. An appreciable percentage of radioactivity
      was also recovered as free cholesterol, especially during the embryonic phase.
      The developmental patterns of amino acid synthesis from acetoacetate and 3
      hydroxybutyrate were similar in both tissues: a clear increase after hatching was
      followed by a decrease at day 4 of neonatal life. Acetoacetate was a better
      substrate for amino acid synthesis than 3-hydroxybutyrate during the embryonic
      development in both tissues. Oxidation of both precursors to CO2 strongly
      decreased between 15 and 21 days of embryonic development both in brain and
      spinal cord.

PMID- 8255361
TI  - Substrate-stimulated oxygen consumption by isolated rat brain microvessels in the
      presence and absence of ATP.
AB  - We report here properties of isolated brain microvessels such as the rate of
      oxygen consumption with different substrates; the permeabilizing effect of added
      ATP is studied. With the isolation procedure presented the cerebral endothelium
      has a metabolic activity comparable to that reported in the literature. The
      respiratory rate of the microvessels is not affected by the addition of ATP,
      whereas it is significantly increased by addition of succinate and alpha
      chetoglutarate. The exposure of the isolated brain capillaries to ATP, in a
      Ca(2+)-free medium, increases the uptake of 6-carboxyfluorescein. This may be due
      to pores opened by ATP in the endothelial cell membrane in the absence of
      divalent cations.

PMID- 8255362
TI  - N-terminal arginylation of proteins in explants of injured sciatic nerves and
      embryonic brains of rats.
AB  - Posttranslational modification of proteins by arginine and lysine has been
      demonstrated in crude extracts of vertebrate nerves and brain but not in intact
      cells. In the present experiments we have exploited the fact that Arg is added
      posttranslationally only at the N-terminus of target proteins, to demonstrate
      these reactions in intact cells of sciatic nerves and embryonic brains of rats.
      Sciatic nerves were crushed in anaesthesized rats and 2 hrs later segments of
      nerve, including the site of the crush, were removed and incubated in media
      containing [3H]Arg. Incorporation of [3H]Arg into total proteins was analyzed by
      acid precipitation and the presence of label at the N-terminus was determined by
      a modification of the Edman degradation procedure. Approximately 25% of protein
      bound [3H]Arg was released from the N-terminus by the Edman reaction indicating
      that it was added posttranslationally rather than through protein synthesis. N
      terminal labeling was not detectable in nerves not crushed prior to explant and
      incubation. Slices of embryonic day 20 visual cortex, when incubated under
      similar conditions as injured sciatic nerves, also showed approximately 25% of
      the protein incorporated [3H]Arg at the N-terminus, while arginylation was not
      detectable in adult rat brain slices. Since Lys is not added posttranslationally
      to the N-terminus, we have attempted to observe lysylation of proteins in intact
      cells by using cycloheximide (Cx) to block protein synthesis without interfering
      with protein modification. The posttranslational incorporation of Arg/Lys into
      proteins was found to be insensitive to up to 2.0 mM Cx in tissue extracts (in
      vitro).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255363
TI  - Potent, extra-channel influence of several calcium-channel modulators on striatal
      binding of [3H]tyramine.
AB  - A number of Ca(2+)-, K(+)-, and Na(+)-channel modulators has been tested with
      respect to their effects on [3H]tyramine (TY) binding, as a putative marker for
      the vesicular dopamine (DA) transporter in striatal membrane preparations
      containing vesicle ghosts. Among organic Ca(2+)-channel modulators, the
      diphenylalkylamines tested consistently inhibited TY binding: the order of
      potency was prenylamine > lidoflazine > flunarizine > cinnarizine, with Ki values
      of 0.1, 0.2, 0.5 and 1.2 microM, respectively. Low (up to 100 nM) concentrations
      of prenylamine did competitively inhibit TY binding, and higher concentrations
      provoked a mixed-type inhibition. Furthermore, LIGAND-analysis of competition
      curves revealed a high- and a low-affinity binding site for prenylamine and
      flunarizine. The TY binding process was also sensitive to selected K(+)- and
      Na(+)-channel modulators. Since several Ca(2+)-antagonists are known to affect
      H(+)-ATPase and the bioenergetics of catecholamine storage vesicles in chromaffin
      granules, thus affecting monoamine storage, the energy requirements for the
      formation of the TY/carrier complex were here assessed, assuming similarity
      between chromaffin granules and synaptic vesicles. TY binding, though not
      reflecting endovesicle-sequestered TY, was indeed strongly sensitive (with Ki
      coefficients in the fM or low nM range) to the dissipation of the vesicular
      transmembrane proton concentration (delta pH), electrical (delta psi), and proton
      electrochemical (delta microH+) gradients, provoked by a number of specifically
      targeted agents. It is concluded that Ca(2+)-channel agents of the
      diphenylalkylamine group may directly affect striatal TY binding due to an
      extrachannel-regulated competition with TY for the vesicular carrier of DA, as
      well indirectly, by disruption of the transmembrane energization of the reserpine
      sensitive carrier.

PMID- 8255364
TI  - Effects of CGP 28014 on the in vivo release and metabolism of dopamine in the rat
      striatum assessed by brain microdialysis.
AB  - The effects on rat striatal dopamine (DA) metabolism of systemic and local
      administration of CGP 28014, an inhibitor of catechol-O-methyl-transferase
      (COMT), were studied by in vivo microdialysis. CGP 28014 (30 mg/kg i.p.)
      significantly reduced the levels of homovanillic acid (HVA), but did not modify
      DA and 3,4-dihydroxyphenylacetic acid (DOPAC). The intrastriatal administration
      (via the microdialysis probe) of 5, 7.5, 10, and 20 mM of CGP 28014 elicited a
      concentration-dependent, several-fold increase in extracellular DA but did not
      alter the levels of HVA and DOPAC. Thus, the effects of CGP 28014 observed after
      i.p. injection (decrease in HVA levels) are different from those measured after
      intrastriatal administration (increase in DA release). Therefore, the inhibition
      of COMT is likely to be due to the action of a metabolite of CGP 28014 formed in
      the periphery and not in the brain.

PMID- 8255365
TI  - Monoamine oxidase inhibitors and the cheese effect.
AB  - The behavior of inhibitors of monoamine oxidase-A (MAO-A) is considered in terms
      of the possibility of having an effective antidepressant that does not give rise
      to hypertensive interactions with dietary tyramine. Studies with punch-biopsy
      samples of human intestine and rat intestinal samples show MAO-A to be the
      predominant form of the enzyme in both species. Transport studies with everted
      rat intestinal preparations indicate that tyramine is extensively metabolized
      during transport through the intestine. Selective inhibition of MAO-A by
      clorgyline results in a large increase in the amount of unchanged tyramine
      transported, whereas selective inhibition of MAO-B with L-deprenyl (selegiline)
      has no significant effect. The behavior of reversible MAO-A inhibitors can
      significantly reduce, but not entirely eliminate, these effects on the intestinal
      metabolism of tyramine, but only if the inhibition is competitive in nature.

PMID- 8255366
TI  - Ganglioside composition of subcellular fractions, including pre- and postsynaptic
      membranes, from Torpedo electric organ.
AB  - Gangliosides were isolated from four subcellular fractions of the electric organ
      of Torpedo marmorata: synaptosomes, presynaptic membranes, postsynaptic
      membranes, and synaptic vesicle membranes. This exploited a principal advantage
      offered by this tissue: facile separation of pre-and postsynaptic elements. Total
      ganglioside concentration in presynaptic membranes was approximately twice that
      of synaptosomes and 15 times that of postsynaptic membranes (47.7, 24.4, and 3.21
      micrograms of lipid sialic acid per mg protein, respectively). Synaptic vesicle
      membranes had the highest overall concentration (78.9) relative to protein, but a
      concentration approximately comparable to that of presynaptic membranes when
      expressed relative to phospholipid. The thin-layer patterns of these two
      fractions were similar, both in terms of total pattern and the specific pattern
      of gangliotetraose structures as revealed by overlay with cholera toxin B
      subunit; these were notable for the paucity of monosialo structures and the
      virtual absence of GM1. Postsynaptic membranes, on the other hand, had a
      significantly higher content of monosialogangliosides including the presence of
      GM1. The synaptosomal pattern resembled that of the presynaptic membranes and
      synaptic vesicles. Thus, a clear difference in ganglioside pattern could be
      discerned between the pre- and postsynaptic elements of the electric organ.

PMID- 8255367
TI  - Effect of acetyl-L-carnitine on lipid peroxidation and xanthine oxidase activity
      in rat skeletal muscle.
AB  - It has been reported that acetyl-L-carnitine (AcCn) can reduce the degenerative
      processes in the central nervous system of rats, modify the fluidity of membranes
      and decrease the accumulation of lipofuscins in neurones. In light of these
      considerations we have assayed the in vitro effect of acetyl-L-carnitine on
      spontaneous and induced lipoperoxidation in rat skeletal muscle; in addition, the
      effect of AcCn on XD/XO ratio was evaluated. The presence of AcCn (10-40 mM) in
      incubation medium significantly reduced MDA and conjugated diene formation in rat
      skeletal muscle; moreover, a significant decrease in induced MDA levels was
      observed when microsomal preparation where incubated in the presence of 10-40 mM
      AcCn. Since a significant reduction of XO activity was detected in the presence
      of 10-80 mM AcCn, the reduced lipid peroxidation by AcCn seems to be due to an
      inhibition of XO activity.

PMID- 8255369
TI  - Changes of NMDA receptor binding in spontaneously epileptic rat and parent
      strains.
AB  - We measured the binding of [3H]3-[(+/-)2-carboxypiperazin-4-yl] propyl-1
      phosphonic acid ([3H]CPP), a competitive ligand for N-methyl-D-aspartate (NMDA)
      receptors, in double mutant spontaneously epileptic rats (SER: zi/zi, tm/tm) and
      their parent strains, zitter rats and tremor rats, and WTC rats (control rats
      from tremor rats derived from Kyoto:Wistar rats) before and after the onset of
      seizures in tremor rats and SER. Significantly lower [3H]CPP binding receptor
      density (Bmax) was found in the cortex of SER and zitter rats at 12-15 weeks of
      age than in that of WTC rats and tremor rats, and at 4 weeks of age the Bmax in
      zitter rats was lower than that in the other strains. The reduction of Bmax in
      SER at 12-15 weeks of age may reflect a down regulation of NMDA receptors due to
      repetitive tonic seizures in SER.

PMID- 8255368
TI  - Clinical pharmacology of the new COMT inhibitor CGP 28,014.
AB  - CGP 28,014 is a specific inhibitor of catechol-O-methyltransferase (COMT) in
      vivo. In humans, the inhibition was assessed by measuring urinary excretion of
      isoquinolines and with the levodopa test. Following administration of CGP 28,014,
      urinary excretion of isoquinolines was significantly increased. In rats, CGP
      28,014 reduced plasma and striatal concentrations of 3-O-methyldopa (30MD) in a
      dose-dependent manner. Acute and subchronic administration of CGP 28,014 alone or
      in combination with the peripherally acting decarboxylase inhibitor benserazide
      decreased plasma 30MD as an index of COMT inhibition by about 50%. There seems to
      be a close relationship between the time-course of plasma concentrations of CGP
      28,014 and the extent of COMT inhibition assessed by the 30MD/DOPA ratio in
      plasma.

PMID- 8255370
TI  - The determination of hydroxydopamines and other trace amines in the urine of
      parkinsonian patients and normal controls.
AB  - 5- and 6-Hydroxydopamine, which we had earlier identified as naturally occurring
      amines in human urine, were quantified in Parkinson's patients treated with L
      DOPA, Parkinson's patients whose treatment did not include L-DOPA and in age
      matched controls. Analysis was carried out by GC-MS of the
      ditrifluoromethylbenzoyl-trimethylsilyl (DTFMB-TMS) derivatives of the compounds.
      The concentrations of 5- and 6-hydroxydopamine in the urine of DOPA treated
      Parkinson's patients were significantly higher than the concentrations from
      patients not treated and from normal controls. Urinary dopamine levels were
      greatly elevated in DOPA treated Parkinson's patients while p-tyramine levels
      were suppressed. No marked differences were seen between the three groups in
      terms of the urinary concentrations of any of the other amines measured.

PMID- 8255371
TI  - Analysis of biogenic amines in plasma of hypertensive patients and a control
      group.
AB  - Procedures were developed for the determination of 17 circulating amines using
      gas chromatography-negative ion chemical ionisation mass spectrometry. The amines
      were quantified against their appropriate deuterated isotopomers. The mean
      concentrations and ranges of catecholamines and trace amines were high compared
      with previous studies. In comparison with nonhypertensives, plasma from
      hypertensives had higher concentrations of the following amines: noradrenaline (t
      = 4.0%); normetanephrine (t = 6.1%) and metanephrine (t = 1.9%). There were no
      significant differences between 5HT levels in plasma from hypertensives and
      controls. The following trace amines could be detected in variable amounts in
      plasma: p-tyramine, m-tyramine, p-octopamine, m-octopamine, p-synephrine, m
      synephrine, and salsolinol. The trace amines melatonin, N-acetyl 5HT, tryptamine,
      6-hydroxymelatonin and 5-methoxytryptamine could not be detected in plasma with
      limits of detection lying in the range 20-100 pg ml-1.

PMID- 8255374
TI  - [MRI findings and endocrinological dysfunction in hemorrhagic pituitary adenoma].
AB  - Magnetic resonance image (MRI) findings, intraoperative macroscopic findings and
      endocrinological functions were reported in 13 cases of hemorrhagic pituitary
      adenoma (HPA) according to clinical severity. The cases were divided into 3
      groups: (1) classical pituitary apoplexy (PA) (n = 2), (2) subacute PA (n = 4),
      (3) asymptomatic HPA (n = 7). Based on MRI intensity and intraoperative findings,
      there were 7 cases with hemorrhagic PA and 5 with necrotic cyst formation. MRI
      intensities predicted the cyst contents, either hemorrhagic or xanthochromic,
      more accurately than CT findings. In addition, two classical cases of the PA
      group disclosed niveau formation on MRI, but MRI intensity in the first case
      differed from that in the second case. Classical PA of the first case occurred
      during the pregnancy. MRI intensity in the case 7 months after the onset
      disclosed high intensity of the upper part and normointensity of the lower part.
      T1 weighted image and proton image showed homogeneous intensity. On the contrast,
      PA of the second case showed water-like intensity on the upper part and
      methemoglobin-like intensity on the lower part. These different MRI intensities
      suggest different etiologies of niveau formation. MRI findings in the first case
      may indicate the chronic stage of massive intratumoral hemorrhage but the
      mechanism may be the same in both cases. From MRI intensity and clinical course,
      the cause of niveau formation in the second case is similar to that found in the
      literature. That is, hemorrhage was thought to have occurred in the pre-existing
      cyst cavity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255372
TI  - Dopamine metabolism and free-radical related mitochondrial injury during
      transient brain ischemia in gerbils.
AB  - Regional extracellular release of dopamine (DA) and its metabolites, 3,4
      dihydroxy-phenylacetic acid (DOPAC), homovanillic acid (HVA) and 3
      methoxytyramine (3-MT) was measured in gerbils (with or without pargyline
      pretreatment) subjected to bilateral carotid artery occlusion (15 min) and
      various periods of recirculation (up to 6 hr), utilizing intracerebral
      microdialysis and high-performance liquid chromatography (HPLC) with
      electrochemical detection. Mitochondrial monoamine oxidase (MAO) and superoxide
      dismutase (SOD) activities and in vitro stimulated lipid peroxidation (TBARM)
      were determined in separate experimental groups of animals. The ischemically
      induced DA release, decrease of MAO-derived DA metabolites DOPAC and HVA, and
      accumulation of 3-MT were potentiated and prolonged by pargyline pretreatment.
      Mitochondrial MAO and SOD activities were significantly reduced during ischemia
      alone and up to 1 hr of reperfusion, whereas TBARM was enhanced during reflow
      only. The data suggest that reduced activity of mitochondrial antioxidative
      enzyme(s) but not DA metabolism by MAO may contribute to free radical-mediated
      injury of (mitochondrial) membranes.

PMID- 8255375
TI  - [Opening of the carotid canal in the skull base surgery: drilling of the carotid
      canal triangle].
AB  - With the recent advance in skull base surgery, approaches to the cavernous sinus
      and frontal skull base have been established and introduced positively. The
      author has applied extensive transbasal approach to lesions in the frontal skull
      base, and transzygomatic approach to those in the middle skull base, but since
      the fact that the internal carotid artery runs inside the temporal bone restricts
      surgical procedure for lesions extending not only to the middle skull base but to
      the infratemporal fossa, preservation of the internal carotid artery during
      surgery is demanded. Radical surgery was performed for 5 patients with malignant
      tumor occupying the infratemporal fossa, resulting in successful en-bloc
      resection of the tumor by securing a substantial operative space during surgery
      after early opening of the carotid canal for preservation of the internal carotid
      artery. In opening the carotid canal, the carotid canal triangle is first
      identified, then its bone is shaved and cut as far as the spine of the sphenoid,
      allowing a look at the inside of the tumor, or a view of the internal carotid
      artery, that permits en-bloc resection of the tumor. Representative cases are
      reported here and microanatomical information for surgical procedure in opening
      the carotid canal is also presented with the relevant literature.

PMID- 8255373
TI  - Site and mechanism of behavioral tolerance to cocaine: a study of dopamine
      release in Wistar-Kyoto and spontaneously hypertensive rats.
AB  - Wistar-Kyoto and spontaneously hypertensive rats received i.v. infusions of
      cocaine hydrochloride (60 mg/kg per day) for 3, 7, and 14 days, or saline for 7
      days. Acute cocaine challenge (40 mg/kg, s.c.) was given to treated and control
      rats 24 hr after the termination of each infusion period. There were no strain
      differences in brain levels of cocaine during cocaine infusion, nor after cocaine
      challenges. There were no strain differences in resting levels of [3H]dopamine
      release. Release of [3H]dopamine decreased in nuclei accumbens of 7- and 14-day
      cocaine-infused animals. Release of [3H]dopamine was maximal in both brain
      regions 2 hr after acute cocaine challenge. After 14 days of cocaine infusion,
      cocaine challenge in both strains reduced [3H]dopamine release in the nucleus
      accumbens, but not in the striatum; the reduction being greater in Wistar-Kyoto
      rats. The behavioral tolerance which accompanies similar cocaine infusion
      regimens may be related to striatal "tolerance" to cocaine-induced dopamine
      release.

PMID- 8255376
TI  - [Significance of serum neuron-specific enolase levels after head injury].
AB  - Enolase is an enzyme involved in glycolysis and neurospecific enolase (NSE) has
      two types of isoenzyme (alpha gamma and gamma gamma enolase). Found in nerve
      cells and axons, the NSE is reported to be released into the serum and
      cerebrospinal fluid following nerve injury. We recently analyzed serum NSE levels
      in 47 patients with solitary head injury who were transported to our center
      immediately after injury. There were 35 men and 12 women, with a mean age of 35.1
      years. In each case, blood was sampled within 8 hours after injury. Serum NSE was
      measured and analyzed in relation to the level of consciousness (Japan Coma
      Scale) upon admission, the modified Araki's classification, the presence or
      absence of skull fracture, findings from computed tomography (CT) scans and the
      prognosis according to the Glasgow outcome scale. Differences were compared by t
      test to determine significance. When the level of consciousness was compared with
      the serum NSE level upon admission, the NSE level was significantly higher in
      patients showing a three digit code disturbance of consciousness than in the
      other patients (p < 0.005). When NSE was analyzed in relation to the modified
      Araki's classification, the NSE level for the prolonged type with focal signs was
      higher than the NSE level for any other type (p < 0.001 compared to the transient
      type). The NSE level was significantly higher in patients with skull fracture
      than in patients without skull fracture (p < 0.01). The NSE level was
      significantly higher in patients showing contusion on CT scans than in patients
      without contusion (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255377
TI  - [Sinus thrombosis during CDDP and VP-16 (PE) therapy for suprasellar germ-cell
      tumor: case report].
AB  - A case of sinus thrombosis occurring during combination chemotherapy with CDDP
      and VP-16 (PE) for a suprasellar germ-cell tumor is presented. A 5-year-old girl
      developed polyuria, polydipsia and headache in April, 1991 and became unconscious
      on May 10, 1991, when MRI and CT demonstrated a suprasellar tumor and marked
      hydrocephalus. After a ventriculo-peritoneal shunt operation, radiotherapy and
      two courses of PE therapy were carried out. During the second course of PE
      therapy, diabetes insipidus became quite difficult to control and severe
      hypovolemic hypernatremia developed. While it was being treated, the patient
      developed a clonic convulsion of her left extremities and visual disturbance. CT
      scan demonstrated a right parietal hemorrhagic infarction and IV-DSA suggested
      thrombosis of the superior sagittal sinus. Laboratory data disclosed DIC. The
      main cause of sinus thrombosis in this patient was considered severe dehydration.
      It is also possible that cisplatin and steroid played a role. In addition to
      these, dysfunction of hypothalamus, which is one of the regulatory centers of the
      plasma concentration of factor VIII, may have contributed to the acceleration of
      blood coagulation. This case re-emphasized the importance of preventing
      dehydration and monitoring the blood coagulation fibrinolytic system during PE
      therapy in patients with a suprasellar germ-cell tumor accompanied with diabetes
      insipidus.

PMID- 8255378
TI  - [A case of primary intracranial choriocarcinoma with a carotid-cavernous
      fistula].
AB  - A 14-year-old Japanese girl was admitted to Kosei General Hospital on May 28,
      1987 because of disturbance of visual acuity, bitemporal hemianopsia and general
      fatigue. About two months before, she had noticed disturbance of visual acuity
      and headache. The CT scans demonstrated iso density mass in the chiasmatic region
      with ring enhancement. Bilateral carotid angiograms showed bilateral carotid
      cavernous fistulas. The serum HCG rose to 13000 IU/ml (HCG-beta, 480 ng/ml)
      whereas the urinary level was 2200 mIU/ml and alpha-feto protein was normal. A
      diagnosis of choriocarcinoma was made. Radiation therapy and combined
      chemotherapy (cisplatinum, vinblastine, bleomycin) were begun. But radiation and
      chemotherapy had little effect. On June 12, 1987, chest X-ray film showed several
      abnormal shadows in both lungs, and her general condition continued to
      deteriorate. She died on June 21, 1987. Histologic examination of the tumor
      disclosed cytotrophoblastic cells and syncytiotrophoblastic cells with extensive
      hemorrhage and necrosis. Extracranial metastasis was found only in both lungs.

PMID- 8255379
TI  - [Surgical decompression for the C-1 and C-2 sensory roots and upper cervical cord
      in a case with cervical myelopathy and occipital neuralgia due to bilateral
      fenestration of vertebral artery: a case report].
AB  - A case of bilateral fenestration of the vertebral artery at the level of the
      atlas in a patient who had occipital neuralgia and cervical myelopathy is
      presented. MRI and vertebral angiogram demonstrated the fenestrated vertebral
      artery compressing the upper cervical cord. Surgical decompression for the C-1
      and C-2 sensory roots and the upper cervical cord was performed. Fenestration of
      the vertebral artery is mostly of no clinical significance. However, considering
      the pathway of the fenestrated vertebral artery, it is quite possible that the
      fenestrated vertebral artery might compress the neural structures, resulting in
      some clinical problems. Although occipital neuralgia may result from a variety of
      causes, this case was caused by the fenestrated vertebral artery compressing the
      C-1 and C-2 sensory roots. The authors wish to emphasize that microsurgical
      vascular decompression may be the only effective treatment in such cases as well
      as in facial spasm and trigeminal neuralgia.

PMID- 8255380
TI  - [Peduncular hallucination in brain stem cavernous angioma: a case report].
AB  - A case of brain stem cavernous angioma associated with peduncular hallucination
      is reported. A 68-year-old man was admitted with complaints of left sensory
      disturbance. On the evening of the first hospital day, he developed vividly
      formed hallucinations. The hallucinations were accompanied by sleep disturbance
      and agitation. At approximately 2:00 am, he began to feel as though he could see
      his daughter watching television in a room. At one point he saw vivid pictures.
      MRI revealed a round mass with a mixed signal intensity core surrounded by a low
      signal intensity rim in the right brain stem. On the 10th hospital day, there
      were no hallucinations. On October 12th suboccipital craniectomy was performed
      and cavernous angioma and the surrounding hematoma was partially removed. Soon
      after that the patient was discharged with improvement of both ocular movement
      and left-sided sensory disturbance.

PMID- 8255381
TI  - [Aneurysmal bone cyst of the sixth cervical spine: case report].
AB  - A 19-year-old girl was admitted with a history of difficulty in moving her neck
      for several years and a sudden onset of neck pain three months before. Plain
      radiographs of the cervical spine revealed destruction of the left half of the
      6th cervical body with an expansive soap-bubble appearance. Neurological
      examination on admission was within normal limits. The angiography and bone
      scintigraphy revealed no abnormality. MRI of T1-weighted image showed a cystic
      lesion with various signal intensities. T2-weighted image demonstrated a
      hyperintense balloon-like lesion in the vertebral body and left lamina. At
      surgery, a cystic tumor was fully extirpated by the posterior approach and the
      bony defect was packed with apatite granules. She was discharged without any
      neurological deficits. This disease should be considered as one of the etiologies
      when a patient with difficulty in neck movement is encountered in young
      generation.

PMID- 8255382
TI  - [A case of metastatic spinal tumor from renal cancer reduced by interferon
      alpha].
AB  - A case of metastatic spinal tumor from renal cancer reduced by interferon-alpha
      is reported. A 54-year-old man was admitted to Tane General Hospital on April 12,
      1990, with the complaint of difficulty in walking. Abdominal CT scan revealed
      right renal carcinoma, and MRI demonstrated metastatic spinal tumor at Th6, which
      was mainly occupying the entire lamina, spinous process and right pedicle of Th6.
      Nephrectomy was performed and, instead of operating on the spinal lesion, the
      patient was given follow-up treatment with administration of interferon-alpha (5
      million units twice a week) and steroid. 1 year and 6 months later the patient's
      walking ability began to deteriorate and paraparesis progressed, although the
      size of the metastatic spinal tumor had gradually reduced. This was thought to be
      because of atrophy of the legs due to prolonged bed rest and steroid
      administration. Laminectomy with total removal of the tumor was performed on
      January 16, 1992. In the 12 months postoperatively, there has been neither
      recurrence nor remote metastasis seemingly due to the administration of
      interferon-alpha. This appears to be the first report of metastatic spinal tumor
      from renal cancer reduced by interferon-alpha.

PMID- 8255383
TI  - [A case of tectal glioma].
AB  - A case of tectal glioma with mild choked disc is reported. An 11-year-old boy was
      admitted to our hospital because of visual disturbance and choked disc.
      Neurologically, the patient had nothing but choked disc. Magnetic resonance
      imaging (1.5T) was performed. Relative T1 weighted image showed a lesion of low
      signal intensity, and T2 weighted image showed high intensity, about 1.0 x 1.0 cm
      in size, at the pineal region. The sagittal view showed a mass at the tectum, and
      stenosis of the aqueduct. It was diagnosed as tectal glioma. Left occipital
      craniotomy was performed and the tumor was removed subtotally. Histological
      examination demonstrated a fibrillary astrocytoma. Radiochemotherapy was
      performed postoperatively. Tectal glioma is very rare. The differential diagnosis
      from germ cell tumor or pineal cyst is essential for treatment. The authors
      performed an operation in order to remove the tumor and determine the course of
      treatment.

PMID- 8255384
TI  - [Primary malignant lymphoma of the skull presenting a huge mass lesion: case
      report].
AB  - A rare case of primary malignant lymphoma of the skull presenting a huge mass
      lesion is reported. A 65-year-old male was admitted complaining of a huge scalp
      mass (largest 13 x 9 x 4 cm) which was growing rapidly. On admission he showed
      hemiparesis. The craniogram revealed a large osteolytic lesion of the right
      parietal bone. Computed tomography and magnetic resonance images revealed a huge
      tumoral mass lesion expanding from the epidural to the subcutaneous space at the
      frontoparietal region. The angiogram showed marked tumor stain feeding from the
      bilateral middle meningeal artery and the superficial temporal artery. On
      operation, the tumor was shown to be elastic soft, and existed in the epidural
      and subcutaneous space. It was invading the diploic, with infiltration into the
      dura. The tumor was detached from the dura matter and totally resected. The
      histological diagnosis was malignant lymphoma (B cell type). After the operation,
      the patient's left hemiparesis improved without additional neurological deficit.
      Bone and tumor scintigraphy disclosed no uptake other than that of the head. The
      tumor was diagnosed at primary malignant lymphoma of the skull. After 50-Gy
      radiation and chemotherapy, the postoperative course was uneventful. Although the
      number of reports on malignant lymphoma has increased recently, there are only 15
      case reports concerning those in the skull. The neuroradiological findings and
      differential diagnosis of malignant lymphoma in the skull were mainly discussed.

PMID- 8255385
TI  - [Clinicopathological concepts and classification of diffuse brain injury].

PMID- 8255386
TI  - [Direct clipping of paraclinoid large aneurysms using retrograde balloon suction
      decompression].

PMID- 8255387
TI  - [Gamma-radiosurgery of metastatic brain tumors].
AB  - Twenty-six cases of various brain metastases were treated with Gamma-knife. Their
      primary sites were: lung in 13, colon in 5, breast in 2, kidney in 2, liver in 1,
      ovary in 1, and a malignant melanoma. The origin of one case was not verified.
      There were 11 single and 15 multiple metastases. In total 70 tumors were
      involved. Following localization with MRI and dose planning using a computer
      system, radiosurgery was carried out. Tumors were treated with the maximum dose
      between 24 and 50Gy, and with the marginal dose between 12 and 25Gy. Early follow
      up results demonstrated favorable responses chiefly by tumor shrinkage, central
      tumor necrosis or by decreased peritumoral edema. In fact after radiosurgery, the
      rates of tumor shrinkage were 55.7%, 61.8% and 66.7% at 3, 6 and 9 months
      respectively. The tumor control rates, including regressed and stable tumors,
      were 98.6%, 97.1 and 85.7 at 3, 6 and 9 month intervals respectively. Meanwhile,
      14 cases were neurologically improved, and another 4 showed either no perceivable
      change. Neurological deterioration occurred in 4 cases by progression of brain
      metastasis in 2 and by perifocal edema after radiosurgery. Recurrent brain
      metastases occurring after radiosurgery were treated with a repetition of Gamma
      knife surgery in 4 cases, resulting in good tumor control. In conclusion most of
      the brain metastasis can be well controlled by radiosurgery for relatively long
      period of time.

PMID- 8255388
TI  - [High dose nicardipine therapy for delayed cerebral vasospasm after aneurysmal
      subarachnoid hemorrhage].
AB  - The effect of high dose nicardipine on delayed cerebral vasospasm was studied in
      33 patients with aneurysmal subarachnoid hemorrhage (SAH). Intravenous infusion
      of nicardipine started before or immediately after early operation. The dosage
      was from 4 to 10 mg/h with an average of 7.4 mg/h. The duration was from 2 to 17
      days with an average of 12.3 days. Symptomatic vasospasm was observed in only one
      (3%) out of 33 patients. The remaining 32 patients (97%) showed neither ischemic
      symptoms nor low-density areas on computed tomography. Severe angiographical
      vasospasm was diagnosed in 3 patients, who entered hospital on day 3 to 5 after
      initial attacks. They were operated upon on day 4 to 6 under the administration
      of nicardipine before or immediately after the operation. No patients showed
      symptomatic vasospasm and angiographical vasospasm was improved markedly. The
      present study demonstrated that high dose nicardipine appeared to prevent both
      brain ischemia and angiographical vasospasm after aneurysmal SAH.

PMID- 8255389
TI  - Restoration by bromocriptine of glucocorticoid receptors and glucocorticoid
      negative feedback on prolactin secretion in estrogen-induced pituitary tumors.
AB  - We previously reported a reduction of glucocorticoid receptors (GCR) in
      diethylstilbestrol-induced pituitary tumors (DES-T) in rats. Presently, we found
      that bromocriptine (BROM) treatment increased the levels of GCR in DES-T,
      demonstrated by steroid binding assays and immunocytochemistry using a monoclonal
      antibody against the type II GCR. We also found that the high content of nuclear
      estradiol receptors in the adenomata and the elevated levels of PRL in serum of
      DES-T were significantly reduced after BROM treatment. In parallel studies, PRL
      secretion was measured after administration of ether stress. In controls, serum
      PRL markedly increased after ether and this effect was blunted by prior
      dexamethasone (DEX) administration, due to the steroid negative feedback on PRL
      secretion. In animals with DES-T, ether stress had no effect on serum PRL, and
      the inhibition by DEX was lost unless they received BROM, which restored the
      negative feedback of DEX on serum PRL. Although increases of PRL titers in
      pituitary tumors may be due to estrogenic stimulation of lactotroph proliferation
      and function, coupled to absent dopaminergic inhibition on these cells, other
      mechanisms are possible. In this respect, inefficient steroid negative feedback
      on PRL synthesis due to down-regulation of GCR may contribute to
      hyperprolactinemia. This mechanism is supported from the restoration of GCR and
      steroid negative feedback on serum PRL by treatment of tumor-bearing rats with
      BROM.

PMID- 8255390
TI  - Dopamine regulation of swim stress induction of the pituitary intermediate lobe
      proopiomelanocortin system.
AB  - Previous studies have indicated that 30 min of swimming in room temperature water
      is a potent stimulus for the secretion of beta-endorphin (beta E) from the
      intermediate lobe (IL) of the pituitary in rodents. Repeated daily challenge with
      this paradigm over days to weeks leads to a progressive increase in
      proopiomelanocortin (POMC)-derived IL peptides and POMC mRNA levels as well as an
      increase in the stimulated secretion of beta E in response to rechallenge with
      swim. The current studies were undertaken to examine the possible role of
      dopamine systems in mediating swim stress-induced changes in IL beta E
      biosynthesis and release. Confirming previous results, a 30 min swim stress
      exposure caused plasma concentrations of beta E to increase several fold.
      Apomorphine (APO), a dopaminergic agonist, completely blocked this effect,
      suggesting that dopamine receptors may mediate the acute IL response to swim
      stress. Animals that swam once daily for 14 days displayed elevated beta E levels
      in both the IL and plasma 24 h after the last swim session. In these animals,
      repeated administration of APO did not reverse swim-stress-induced changes in
      beta E. Immediately following an acute-swim rechallenge, animals which had been
      previously swim-stressed for 14 days demonstrated significantly greater beta E
      release than naive animals. Again, an acute injection of APO inhibited the acute
      increase in IL secretion, suggesting that repeatedly swum animals are still
      responsive to the acute effects of APO even though repeated coadministration of
      APO with swim exposure had no effect on IL beta E peptide stores or plasma beta E
      concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255391
TI  - Dissociation of the effect of aminoglutethimide on corticosterone biosynthesis
      from ataxic and hypothermic effects in DBA and C57 mice.
AB  - Adrenalectomy is frequently used to deplete adrenocortical hormones in
      physiological and receptor-binding studies in animals. However, this procedure is
      irreversible, removes both the cortex and medulla, and produces many negative
      side effects such as hypotension and hypoglycemia. Aminoglutethimide is a steroid
      synthesis inhibitor which depletes adrenocortical hormones without these negative
      effects. However, aminoglutethimide itself has been shown to produce behavioral
      and physiological deficits. In the present experiments, dose-response
      relationships were determined for the effects of aminoglutethimide on
      corticosterone levels, motor coordination, and body temperature in C57 and DBA
      mice. Aminoglutethimide (5.4-54 mg/kg) inhibited the increase in plasma
      corticosterone concentrations normally observed in response to restraint stress.
      Only at higher doses (170-1,000 mg/kg) were rotarod performance and body
      temperature affected. The corticosterone response to restraint stress recovered
      fully between 12 and 24 h after aminoglutethimide. In the present study, doses of
      aminoglutethimide were found that temporarily inhibit stressed corticosterone
      release without producing motor deficits and temperature decreases. These results
      indicate that aminoglutethimide is a potential substitute for adrenalectomy in
      studies on the effects of removal of adrenocortical hormones.

PMID- 8255392
TI  - Sex and regional differences in intracellular localization of estrogen receptor
      immunoreactivity in adult ferret forebrain.
AB  - Estrogen receptors were visualized in adult ferret brains using the H222 estrogen
      receptor antibody and immunocytochemical techniques. H222 immunoreactive (H222ir)
      cell nuclei were present in many forebrain regions in gonadectomized ferrets of
      both sexes. In many instances, H222ir cells also had immunoreaction product in
      their processes. All cells with H222ir processes also contained H222ir nuclei.
      More H222ir processes were observed in females in the medial and lateral preoptic
      area/anterior hypothalamus, and at the level of the descending fornix and caudal
      anterior commissure. Quantitative image analysis confirmed that females had
      significantly more (approximately 50%) extranuclear H222 immunoreaction product
      than males in cells in the magnocellular or preoptic subnuclei of the bed nucleus
      of the stria terminalis. Cells in the principal subnucleus of the bed nucleus of
      the stria terminalis and ventrolateral septum were notable for the relative
      paucity of H222ir processes. Sex differences in the intracellular extranuclear
      distribution of estrogen receptor protein in particular brain regions might
      contribute to the differential regulation of estrogen-dependent functions in the
      two sexes.

PMID- 8255393
TI  - Obesity-associated decrease in growth hormone-releasing hormone gene expression:
      a mechanism for reduced growth hormone mRNA levels in genetically obese Zucker
      rats.
AB  - The secretion of growth hormone (GH) is impaired in the genetically obese Zucker
      rat where GH gene expression and plasma GH levels are depressed; however, the
      underlying mechanism of this abnormality remains unclear. We have evaluated the
      potential causative role of hypothalamic GH-releasing hormone (GHRH) and
      somatostatin (SRIH) gene expression in the onset of the decreased GH mRNA levels
      by studying both GHRH and SRIH mRNA and peptide levels in obese and lean rats at
      5 weeks of age when the decrease in GH mRNA is first detected. At that age both
      GHRH content and GHRH mRNA were significantly reduced in obese rats as compared
      to lean controls; hypothalamic SRIH content was also decreased in obese rats, but
      SRIH mRNA levels did not differ. Since GHRH is capable of stimulating GH gene
      expression, the decreased GHRH mRNA level could be a critical factor in causing
      the attenuation in GH gene expression and consequent diminution of circulating
      plasma GH.

PMID- 8255394
TI  - Effects of growth hormone and thyroxine on thymulin secretion in aging rats.
AB  - It is well-established that the activity of the endocrine thymus is under
      neuroendocrine control. In particular, growth hormone (GH) and thyroxine (T4)
      have been shown to be capable of reconstituting thymus function in hormone
      deficient animals. It was therefore of interest to assess the effect of combined
      administration of ovine GH (0.1 mg/100 g BW/day) and T4 (10 micrograms/100 g
      BW/day) on serum thymulin levels in young (5 months), old (21 months) and
      senescent (29-30 months) male Sprague-Dawley rats. Age-matched controls received
      0.1 mg bovine serum albumin/100 g BW daily during the same period (14 days).
      Prolactin (Prl), GH, T4 and triiodothyronine (T3) were measured in serum by
      radioimmunoassay, whereas serum thymulin was determined by rosette bioassay. As
      expected, GH and T4 were lower in the old and senescent controls whereas serum
      Prl displayed a slight age-related increase. No age changes were detected in
      serum T3. Hormone-treated animals showed supraphysiologic levels of both T4 and
      T3, but serum levels were comparable among the three treated age groups for each
      thyroid hormone. Endogenous GH levels were moderately elevated in the treated
      rats. In the control rats serum thymulin showed a marked reduction from 5 to 21
      months of age but no further reduction was observed between 21 and 29-30 months.
      Hormone treatment induced a mean relative increase (% increase relative to age
      matched controls) in serum thymulin of 44, 38 and 48% in young, old and senescent
      rats, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255395
TI  - Short- and long-term effects of perinatal interleukin-1 beta-application in rats.
AB  - Nervous, endocrine and immune systems are regarded as a complex functional unit,
      interacting by their specific chemical messengers-neurotransmitters, systemic
      hormones and hormone-like mediators of immune cells (cytokines). Cytokines are
      known to affect several endocrine axes. Interleukin-1 beta (IL) was administered
      in rats intraperitoneally twice daily from day 17 to 21 of pregnancy. Some of the
      IL-treated mothers were rapidly decapitated 1.5 h after the last injection. The
      fetuses were delivered by cesarean section. Maternal plasma CRF, ACTH and
      corticosterone were found to be significantly elevated. Fetal adrenal and thymus
      weights were lower, and plasma corticosterone did not differ from controls. Fetal
      plasma testosterone was decreased in males, androstenedione was increased in
      females. Open-field testing revealed a higher total locomotor activity of IL
      offspring than of controls. IL offspring showed worse results in Skinner box
      learning than controls. Sexual behavior was only affected in males, showing a
      higher percentage of female-type lordosis behavior after castration and estrogen
      treatment compared to controls. At the age of 6 months responsiveness to 'novel
      environment stress' of IL groups was significantly lower than that of controls in
      terms of plasma corticosterone. These results indicate that prenatal treatment
      with IL-1 beta results in long-lasting alterations in psychomotor development,
      behavior as well as in the neuroendocrine system.

PMID- 8255396
TI  - Induction of FOS immunoreactivity in oxytocin neurons after sexual activity in
      female rats.
AB  - Several lines of evidence suggest that centrally released oxytocin (OT) may act
      in the hypothalamic ventromedial nucleus (VMN) to facilitate sexual behavior in
      female rats primed with estradiol and progesterone. The present experiment used a
      marker of neuronal activation, expression of the transcription factor FOS, to
      locate OT neurons activated during sexual behavior. Sexual behavior significantly
      increased the percentage of OT neurons in the hypothalamic paraventricular
      nucleus (PVN) expressing FOS in rats treated with estradiol and progesterone,
      compared to hormone-treated, nonmated controls. The OT neurons colabelled with
      FOS immunoreactivity were found in regions of the PVN, but not in the supraoptic
      nucleus. As reported by others, FOS expression also was induced in the preoptic
      area and the VMN. Taken together with other evidence, the results are consistent
      with the hypothesis that endogenous OT is involved in female sexual behavior, and
      suggest that the source of oxytocinergic innervation to the oxytocin receptors in
      the VMN may be neurons in the PVN. Interestingly, FOS expression in the VMN
      occurred in cells in the vicinity of OT fibers.

PMID- 8255397
TI  - Melatonin receptors in the lamb pars tuberalis/median eminence throughout the
      day.
AB  - After validation of the methodology, melatonin receptors have been measured by
      binding of (125I)-melatonin to membranes of individual pars tuberalis/median
      eminence of lambs at different times of the day in the course of three
      experiments. Plasma melatonin was assessed by radioimmunoassay 60 min, 30 min and
      just before slaughter. Kd was found in the range of 10-25 pM and did not vary
      with the time of slaughter. Particularly, the mean Kd values were identical and
      equal to 17 pM in animals slaughtered either during the light or the dark phase
      of the day. The pattern of Bmax changes was similar in the three experiments and
      varied significantly (p < 0.001) with the time of the day. The apparent numbers
      of receptors were found to be the highest at the end of the day and at the onset
      of the night and to be the lowest at the end of the night: 63.4 +/- 6.3, 61.4 +/-
      6.5 and 34.4 +/- 2.8 fmol/mg protein (mean +/- SEM), respectively. Values were
      found to be intermediary either at the middle of the day (51.1 +/- 5.3 fmol/mg
      protein) or at the middle of the night (40.4 +/- 6.3 fmol/mg protein).
      Furthermore, plasma melatonin was positively correlated to the melatonin receptor
      number (p < 0.02) but only at the onset of the night. In conclusion, the results
      are strongly suggestive of the existence of a circadian rhythm in the apparent
      number of melatonin receptors in the lamb pars tuberalis/median eminence with a
      possible downregulation occurring during the night.

PMID- 8255399
TI  - Current bibliographies of Neuropeptides prepared by the University of Sheffield
      Biomedical Information Service.

PMID- 8255398
TI  - Binding characteristics of hypothalamic mu opioid receptors throughout the
      estrous cycle in the rat.
AB  - This study presents a detailed analysis of the binding characteristics of
      hypothalamic mu opioid receptors during the different phases of the estrous cycle
      of the female rat. Different groups of adult female rats with a regular 4-day
      estrous cycle were killed by decapitation at 10.00 h of diestrus days 1 and 2, at
      10.00, 12.00, 14.00, 16.00, 18.00 and 20.00 h of the day of proestrus and at
      10.00, 12.00, 14.00, 16.00 and 18.00 h of the day of estrus. At sacrifice, the
      hypothalami of the animals were dissected out, plasma membrane preparations were
      obtained and the binding characteristics (Bmax, Kd) of the specific mu opioid
      ligand dihydromorphine (DHM) on mu opioid receptors were evaluated. Blood has
      been collected from the trunk vessels to monitor with specific radioimmunoassays
      serum levels of LH, estradiol and progesterone. The data obtained indicate that
      in the hypothalamus of female rats with a regular 4-day estrous cycle, the
      binding characteristics of DHM for mu receptors show important variations during
      the different phases of the estrous cycle. In general, the number of mu opioid
      receptors is elevated during the morning of diestrus day 2 and during the day of
      proestrus being maximal at 14.00 h and declining significantly at 18.00 and 20.00
      h of the same day. At estrus, the number of mu receptors appears high at 10.00
      and 16.00 h and low at 12.00, 14.00 and 18.00 h. All these variations take place
      without any significant change of the affinity (Kd) of DHM for the mu
      receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255400
TI  - The effects of chronic glucocorticoid excess, adrenalectomy and stress on
      neuropeptide Y in individual rat hypothalamic nuclei.
AB  - Several lines of evidence indicate a role for neuropeptide Y (NPY) in the
      modulation of the corticotroph axis. In two separate studies reported here, the
      concentrations of NPY and noradrenaline (NA), as well as corticotropin-releasing
      factor (CRF) and arginine vasopressin (AVP), were measured in extracts of
      individual rat hypothalamic nuclei after various manipulations producing either a
      state of chronic glucocorticoid excess or depletion, and also following repeated
      restraint stress. Alterations induced in the activity of hypothalamic neurones
      were inferred from the respective changes in these concentrations. 12 days after
      bilateral adrenalectomy (ADX), NPY levels were decreased by 24% in the arcuate
      nucleus (ARC) and 23% in the paraventricular nucleus (PVN, p < 0.05 vs controls).
      Forced immobilization of the animals for 4 h each day for 9 consecutive days
      (repeated stress) also decreased NPY content of the ARC by 25% (p < 0.01 vs
      controls), an effect blocked by the administration of glucocorticoids. NA levels
      in both hypothalamic nuclei were unaffected by repeated stress or ADX.
      Administration of glucocorticoids in the first of these studies induced decreases
      in NA levels by 15% and 25% in the ARC and PVN respectively (p < 0.05 vs
      controls). However, in subsequent experiments no significant effect of
      glucocorticoids on NA was observed. Our results demonstrate that the activity of
      the hypothalamic NPY-ergic neurones is modulated by glucocorticoids and by
      chronic stress. They also suggest that brainstem catecholaminergic and
      hypothalamic NPY-ergic neurones are differentially affected by altered
      glucocorticoid concentrations or by chronic stress, possibly in a stimulus
      specific way.

PMID- 8255401
TI  - Identification of alpha-carboxamidated and carboxy-terminal glycine forms of
      peptides in bovine hypothalamus, bovine pituitary and porcine heart extracts.
AB  - Two chemical assays have been developed for identifying and quantifying peptides
      which either could be biologically active by virtue of their alpha
      carboxamidation or could be substrates for peptidylglycine alpha-amidating mono
      oxygenase. The first assay is specific for the alpha-carboxamide of peptides.
      Using bis[trifluoroacetoxy]iodobenzene, the alpha-carboxamide was converted via a
      Hoffman reaction into a primary amine, which was then quantified by ninhydrin.
      The second assay is specific for glycine at the carboxy-terminus of a peptide.
      Glycine at the carboxy-terminus was derivatized to form 2-thiohydantoin, which
      was then separated and quantified by reverse phase HPLC. These assays were used
      to detect peptides in HPLC-separated extracts of bovine hypothalamus, bovine
      anterior lobe pituitary and porcine heart which may be of biological interest.

PMID- 8255402
TI  - Use of endoscopic biopsies and microelectrodes to study human gastric acid
      secretion in vitro.
AB  - We have investigated the possibility of measuring acid secretion from human
      gastric mucosa in vitro as a potential pharmacological preparation. We used open
      ended 10 microns-tip, lix-based glass microelectrodes to measure the pH of the
      mucus layer of gastric biopsies superfused with a HEPES buffered solution in an
      organ bath. With no drugs added the pH of the mucus layer of biopsies from the
      body of the stomach stayed constant but the pH of antral biopsies fell slightly
      by a median of 0.12 pH units over 80 min (P < 0.05). Stimulation of the biopsies
      with 1-100 microM histamine produced a dose-dependent decrease in pH which was
      significantly greater in biopsies from the gastric body than from the antrum. 500
      pM pentagastrin produced a median fall in pH of 1.20 (P < 0.01) which was
      prevented by the prior addition of 100 microM omeprazole or 10 microM ranitidine.
      Omeprazole or ranitidine alone produced slight rises in the median pH of 0.47 (P
      < 0.05) and 0.26 (P < 0.05) units respectively. Those biopsies which were
      infected with Helicobacter pylori had a slightly elevated initial pH of about 0.2
      of a pH unit (P < 0.05). This novel system provides a means to study human
      gastric acid secretion in vitro and may be valuable in the testing of new drugs
      on the stomach.

PMID- 8255403
TI  - Bimodal shape of individual variation in behavior of Wistar rats: the overall
      outcome of a fundamentally different make-up and reactivity of the brain, the
      endocrinological and the immunological system.
AB  - An overview of the most important features of the two distinct types of
      individuals which normally co-occur in an unselected population of Wistar rats is
      given. It reveals that the overall make-up and reactivity of the brain, as well
      as the endocrinological and immunological systems differ completely between the
      two types of individuals. Each of these types of individuals has its own
      individual-specific hardware and software to cope with challenges from the
      internal or external environment, requires its own optimal niche, and is
      vulnerable for its own set of stressors.

PMID- 8255404
TI  - Neurobiological concepts of fever generation and suppression.
AB  - Fever is induced by interactions of bacterial pyrogens with cells from the immune
      system, which subsequently release a cascade of cytokines. After intramuscular
      injection of lipopolysaccharide (LPS) from E. coli, increased amounts of tumor
      necrosis factor (TNF) and interleukin-6 (IL-6) can be measured in blood plasma
      and in perfusates of the anterior hypothalamus, where body temperature is
      regulated. These substances are therefore candidates to be involved in the
      modification of thermoregulatory structures leading to the febrile rise in body
      temperature. This increase of body temperature is limited and sometimes even
      prevented by the actions of endogenous antipyretic neuropeptides like arginine
      vasopressin (AVP), adrenocorticotropin (ACTH) and melanocyte-stimulating hormones
      (MSHs) liberated within the brain or systemically during fever. For AVP, most
      experimental evidence confirms antipyretic pathways from the hypothalamic
      paraventricular nucleus to the septal area of the limbic system, which are
      activated during fever and by several stressful stimuli. Fever and endogenous
      antipyresis are interconnected and result from interactions between the immune
      system and the central nervous system.

PMID- 8255405
TI  - Psychophysiology, psychoneuroendocrinology, and the laterality concept of the
      brain.
AB  - Twenty-two patients--11 paranoid schizophrenics and 11 major depressed--were
      investigated by means of a hypothalamic-pituitary challenge (HPC). The latter
      contained insulin, TRH and metoclopramide. Response with regard to blood glucose,
      serum GH, PRL, TSH and cortisol were measured 30, 60, 90, 120 and 180 min after
      the baseline. Temporal alpha power was split into 2 groups with high and low
      alpha power, respectively. The aim was to see whether high cortical-limbic
      hypothalamic-pituitary and hypothalamic-pituitary-adrenal reactivity correlated
      with high temporal alpha power. Poor results were found with regard to diagnoses.
      Only TSH and glucose response were correlated with diagnoses. But, GH and
      cortisol responses reacted in relation to different alpha levels. Cell loss due
      to hormonal stress and consecutive miswiring of axons due to wrong sprouting are
      discussed as possible reasons for abnormal lateralized HPC response.

PMID- 8255406
TI  - Alterations of neuroendocrine brain asymmetry: a neural risk factor affecting
      physical health.
AB  - It was examined whether the specific pattern of brain asymmetry in cerebral
      control of cortisol secretion existing in a specific individual is suitable to
      predict the individual's physical health status. Results indicate that subjects
      with an altered, strong left hemisphere dominance of cortisol regulation show a
      clearly higher amount of physical complaints than subjects with a normal, strong
      right hemisphere dominance. In addition, results suggest that the subjects'
      specific pattern of neuroendocrine brain asymmetry can be used with relatively
      good success to separate individuals with high versus low degrees of physical
      complaints and thus, probably, to predict physical complaints of an individual.

PMID- 8255407
TI  - P-impulsive sensation seeking and its behavioral, psychophysiological and
      biochemical correlates.
AB  - Impulsive unsocialized sensation seeking (ImpUSS) is a major factor discovered in
      factor analyses of scales used in psychobiological research. It is strongly
      convergent with Eysenck's P dimension and conscientiousness in the 'big five'.
      The components of the dimension and the P scale, have been validated as
      correlates of various kinds of disinhibited behaviors, criminality, sexuality,
      and substance use and abuse. ImpUSS is related to a failure in passive avoidance
      learning, probably as a function of impulsivity and attention to reward stimuli.
      Psychophysiological markers for the trait include strong orienting and weak
      defensive reflexes and an augmenting, rather than reducing, of cortical reaction
      to intense stimuli. At the neurochemical level the trait is related to low levels
      of monoamine oxidase (MAO) and the neurotransmitters norepinephrine and
      serotonin, and theoretically high levels of dopaminergic activity. The trait
      components have high heritabilities for a personality trait.

PMID- 8255408
TI  - Lowering of body core temperature by exposure to a cold environment and by a 5
      HT1A agonist: effects on physiological and psychological variables and blood
      serotonin levels.
AB  - The present study was designed to compare the effects of a pharmacologically
      induced decrease in body core temperature to the effects observed with lowering
      of body temperature by exposure to a cold environment. Our special interest was
      the involvement of 5-HT in thermoregulatory responses. Sixty healthy male
      volunteers were randomly assigned to one of the following conditions: exposure to
      normal ambient temperature (28 degrees C) and placebo, exposure to cold ambient
      temperature (5 degrees C) and placebo, or normal ambient temperature and 10 mg of
      the partial 5-HT1A agonist ipsapirone. As indicators of physiological responses
      to lowering of body temperature, tympanic temperature, skin temperature, EMA,
      metabolic rate, and heart rate were monitored and saliva cortisol levels and
      peripheral 5-HT concentrations were determined. In addition, ratings on ambient
      temperature, thermal discomfort, and feelings of irritability were obtained.
      While lowering of body core temperature was associated with marked
      counterregulations (decrease of skin temperature, increase in EMA and metabolic
      rate) and feelings of discomfort, this was not observed with ipsapirone. An
      increase in cortisol levels was primarily observed in the ipsapirone group and
      was not reflected by respective changes in whole blood or platelet 5-HT
      indicating that brain and platelet 5-HT are not related.

PMID- 8255409
TI  - Cholinergic control of cognitive resources.
AB  - In this paper, we describe our approach to the investigation of cholinergic
      modulation of human information processing. In a continuing series of studies
      from our laboratories, we have systematically examined the extent to which
      current psychological models of information processing provide an adequate
      framework for the interpretation of the modulatory effects of cholinergic agents
      on cognitive performance measures. We suggest that the data are consistent with
      the view of attention and memory as processes which operate through a common,
      limited capacity executive mechanism, rather than separable serial processes
      described in the traditional modular models of memory.

PMID- 8255410
TI  - Extrapituitary effects of corticotropin-releasing hormone and thyrotropin
      releasing hormone.
AB  - Besides their regulation of the pituitary-adrenal and pituitary-thyroidal axis,
      respectively, the neurohormones CRH and TRH act within the central nervous system
      to evoke and modulate a number of behavioral and physiological processes. In
      particular, an increase in the sympathetic nervous system and respiratory
      activity has been observed. The data communicated in this review article
      emphasize the role of these neurohormones with regard to the neuroendocrine
      regulation of the autonomic nervous system, sleep and cognitive performance.
      Moreover, a possible therapeutic role is suggested by the beneficial effects in
      patients at risk of hypoventilation-associated disorders.

PMID- 8255411
TI  - Functional recovery and morphological changes after injury to the optic nerve.
AB  - Physiological and morphological parameters of optic nerve lesions followed by
      functional recovery are discussed in detail. To study functional and/or
      morphological recovery processes, a recently developed model of the 'graded optic
      nerve crush' is compared with other models of lesioning. It is concluded that the
      optic nerve crush model is a valuable tool when studying brain repair mechanisms.
      First results show that functional recovery depends on the initial preservation
      of a sufficiently large population of ganglion cells in the retina. It takes
      place despite the progressive loss of retinal ganglion cells during the recovery
      period.

PMID- 8255412
TI  - Psychobiology of coping and defence strategies.
AB  - The stress response should be regarded as an alarm system, occurring whenever
      there is something missing. Lack of information (uncertainty), and the absence or
      loss of control produce alarm, presence of information and control (coping), or
      cognitive defence mechanisms (distorted stimulus expectancies) reduce the alarm.
      Both immune and endocrine parameters of stress are dampened by defence and
      coping. Biologically, these two mechanisms have different time axes. While coping
      is related to the fast catecholamine response, defence is related to the slower
      pituitary-adrenal response. The role of cortisol seems to be to suppress and
      dampen the acute stress response in the later phase, once it has been elicited.
      The relation between stress and health depends on the stress-dampening
      mechanisms, on how the alarm is turned off, why it sometimes seems to be left on,
      and what the consequences really are of leaving the alarm on.

PMID- 8255413
TI  - Indices of mental workload in a complex task environment.
AB  - The aim of the present experiment is to evaluate heart rate variability (HRV) and
      cortisol as indices of mental workload in a complex environment. Heart rate was
      continuously recorded during flight scenarios that differed in difficulty. The
      HRV nicely reflected the changes in difficulty. The results support the idea that
      HRV is a sensitive index for mental workload when tasks are highly demanding and
      subjects are motivated to exert additional effort whenever the task becomes more
      demanding. Cortisol was only slightly increased on the experimental day compared
      to the training day. On the experimental day, post-task levels did not differ
      from pre-task levels. The level of cortisol in saliva was, however, related to
      overall task performance. Subjects who had a high level of cortisol had a low
      level of performance.

PMID- 8255414
TI  - The 'Trier Social Stress Test'--a tool for investigating psychobiological stress
      responses in a laboratory setting.
AB  - This paper describes a protocol for induction of moderate psychological stress in
      a laboratory setting and evaluates its effects on physiological responses. The
      'Trier Social Stress Test' (TSST) mainly consists of an anticipation period (10
      min) and a test period (10 min) in which the subjects have to deliver a free
      speech and perform mental arithmetic in front of an audience. In six independent
      studies this protocol has been found to induce considerable changes in the
      concentration of ACTH, cortisol (serum and saliva), GH, prolactin as well as
      significant increases in heart rate. As for salivary cortisol levels, the TSST
      reliably led to 2- to 4-fold elevations above baseline with similar peak cortisol
      concentrations. Studies are summarized in which TSST-induced cortisol increases
      elucidated some of the multiple variables contributing to the interindividual
      variation in adrenocortical stress responses. The results suggest that gender,
      genetics and nicotine consumption can influence the individual's stress
      responsiveness to psychological stress while personality traits showed no
      correlation with cortisol responses to TSST stimulation. From these data we
      conclude that the TSST can serve as a tool for psychobiological research.

PMID- 8255415
TI  - Immune cell and cortisol responses to physically and pharmacologically induced
      lowering of body core temperature.
AB  - In a placebo-controlled double-blind study described by Rammsayer and co-workers
      in this volume, we investigated the influence of decreased body core temperature
      (BCT) on responses of cortisol and the immune system. As described in the first
      paper, the decrease in BCT was achieved by: (a) exposure to ambient cold
      temperature of 5 degrees C for 20 min (CT group), or (b) application of a 5HT-1a
      agonist under normal temperature conditions (5HT group). A third group serving as
      control was exposed to normal temperature and placebo (NT group). The decrease of
      BCT seen in both CT and 5HT was accompanied by an increase in cortisol. This
      seemed to be due to stress experience in the CT group and to the pharmacological
      challenge in the 5HT group. The number of peripheral CD4+ cells was reduced in
      both experimental groups. This was not mediated by decreased BCT. In the CT group
      the reduction of CD4+ cells showed no relationship to changes in cortisol.
      However, in the 5HT group cortisol could be demonstrated to be the mediator of
      changes in peripheral CD4+ cells.

PMID- 8255416
TI  - Psychophysiological, neuroendocrine and cellular immune reactions under
      psychological stress.
AB  - Emotional stress is often followed by increased susceptibility to infections.
      Natural killer (NK) cells play a major role in the immediate immune response
      controlling this susceptibility. In this study on 45 first-time parachutists, it
      is demonstrated that highly controlled psychological stress increased
      psychophysiological variables, enhanced the secretion of sympathetic-adrenal
      hormones and also led to a significant increase of NK cells and their cytotoxic
      activity followed by a decrease below starting values. This immunological
      alteration is correlated with the secretion of noradrenaline during the emotional
      strain. Quick mobilization of these cytotoxic effector cells is suggested as a
      major mechanism for the effective adaptation of the immune system to stress
      situations.

PMID- 8255417
TI  - Cytokine production during sleep and wakefulness and its relationship to cortisol
      in healthy humans.
AB  - A growing body of evidence indicates that cytokines, especially interleukin-1
      beta, are involved in the regulation of sleep and wakefulness. The aim of the
      present pilot study was to investigate the relationship between interleukin-1
      beta (IL-1 beta) and gamma-interferon (gamma-IFN) production and the regulation
      of sleep and wakefulness. Four healthy male volunteers were investigated. After
      one adaptation night, beginning at 8 a.m. in the morning, the EEG was recorded by
      means of a mobile long-term EEG and blood samples were drawn every 45 min for the
      analysis of IL-1 beta, gamma-IFN and cortisol for 24 h. For the analysis of
      cytokines whole blood cultures were established. After 48 h of incubation in the
      presence of endotoxin Salmonella typhimurium, IL-1 beta and gamma-IFN levels were
      measured in the culture supernatants using specific immunodetection assays.
      Methods of stochastic time series analysis were adopted to evaluate the
      biochemical data. Our results show the capability of cultured blood cells to
      produce cytokines upon endotoxin challenge to be at a maximum around the time of
      sleep onset and during the first hours of sleep, declining during the night to a
      minimum level in the morning hours. The opposite was observed for cortisol. The
      analysis of autocorrelation functions gives evidence of a 24-hour rhythm of
      cortisol and cytokines. The results indicate that the cytokines IL-1 beta and
      gamma-IFN may play a role in sleep regulation.

PMID- 8255418
TI  - Immunological responses to social stress: dependence on social environment and
      coping abilities.
AB  - Social interactions as a consequence of the social position represent stressful
      conditions for the individual. Manipulation of social conditions or forming long
      term social hierarchies by colony aggregation allow to investigate the regulation
      of immune defense mechanisms under seminatural circumstances. The present paper
      describes the effects of dyadic social interaction in male rats with or without
      direct aggressive interactions on some indices of humoral and cellular immunity.
      In addition, for comparative and reference purposes, in one experiment the
      conventional stressor of inescapable footshock was used as well. Primary humoral
      immune response to sheep red blood cell antigen is suppressed by repeated
      experience of both defeat and inescapable footshock. At individual level the
      social stressor is as effective as the conventional stressor of inescapable
      footshock, less individual rats show suppression following the social than after
      the conventional stress. The social stressors, i.e. being exposed to a resident
      or intruder of the territory, facilitate lymphocyte proliferation in the spleen
      by the mitogen ConA and PHA independently of the presence or absence of direct
      aggressive interaction. Finally, the different social stressors have some impact
      on the lymphocyte subpopulation in the spleen. Social stimulation without
      aggressive interactions increases the relative number of T-helper cells, whereas
      defeat leads to an increase in the T-suppressor/cytotoxic subpopulation. The data
      suggest multiple and differential effects of social stress on immune system
      functioning in the rat. Individual characteristics of the coping with stress, the
      social environment, and the immune indices under investigation determine the
      magnitude and direction of the changes in immune functioning.

PMID- 8255419
TI  - Loss of cannabinoid receptors in the substantia nigra in Huntington's disease.
AB  - Previous autoradiographic studies in rats using [3H]CP55,940 have demonstrated
      the cannabinoid receptor to be located on the axon terminals of striatal efferent
      neurons projecting to the globus pallidus and substantia nigra. Because these
      neurons are selectively lost in Huntington's disease, a loss of [3H]CP55,940
      binding is predicted in the substantia nigra of the Huntington's disease brain.
      We have used autoradiography to compare the binding of [3H]CP55,940 in the
      substantia nigra of Huntington's disease and neurologically normal brains. The
      results have demonstrated that cannabinoid receptors in the normal human
      substantia nigra are discreetly localized within the substantia nigra pars
      reticulata. In contrast, the Huntington's disease brains show a massive loss
      (97.5%) of cannabinoid receptor binding in the substantia nigra pars reticulata.
      These results show that in the substantia nigra of the human brain cannabinoid
      receptors are located on striatonigral terminals which degenerate in Huntington's
      disease.

PMID- 8255420
TI  - Mitosis and apoptosis of microglia in vivo induced by an anti-CR3 antibody which
      crosses the blood-brain barrier.
AB  - Microglia, the resident tissue macrophages of the central nervous system, have a
      highly differentiated morphology and do not express many of the antigens
      typically associated with other tissue macrophages. Activation of microglia is
      associated with a change in morphology and an increase in their repertoire of
      antigen expression. Microglia become activated in many neuropathological
      conditions including chronic neurodegenerative diseases and human
      immunodeficiency virus neuropathology, yet little is known of the mechanisms
      involved. Here we demonstrate for the first time that microglia can be activated
      and induced to divide and/or undergo apoptosis via a beta 2-integrin (complement
      receptor type 3, CR3, Mac-1 or CD11b/CD18) using an anti-CR3 monoclonal antibody
      (McAb5C6). This antibody, which has been shown to block myelomonocytic
      recruitment during central nervous system inflammation, is unique in that it can
      cross the intact blood-brain barrier to activate microglia. Since CR3 not only
      binds the iC3b component of the alternative complement cascade but also denatured
      proteins this suggests a potential route for microglia activation in
      neuropathological conditions.

PMID- 8255421
TI  - Kinetics of noradrenaline released by sympathetic nerves.
AB  - At the skeletal neuromuscular junction the released neurotransmitter,
      acetylcholine, is eliminated within some milliseconds. This time course is known
      with great precision through the electrical response of target cells. At the
      sympathetic neuroeffector junction the fast electrical response is not mediated
      by noradrenaline but by a cotransmitter: ATP. The slow electrical response and
      the slow component of smooth muscle contraction are principally mediated by
      noradrenaline. These responses are two orders of magnitude slower than the
      electrical response to ATP. Therefore, great uncertainty remains regarding the
      kinetics of noradrenaline appearance and elimination. Here, the local
      noradrenaline concentration at the surface of the isolated rat tail artery was
      electrochemically monitored in real time using a carbon fibre electrode. We have
      shown that the time course of the neurogenically released noradrenaline is at
      least one order of magnitude faster than the resulting contraction. The kinetics
      of noradrenaline inactivation by neuronal reuptake were also precisely measured.

PMID- 8255422
TI  - Early degeneration of calretinin-containing neurons in the rat hippocampus after
      ischemia.
AB  - The mechanism of delayed death of pyramidal cells in the hippocampal CA1 region
      and the acute death of various types of hilar neurons after ischemia is still
      unknown. Excitotoxicity may play a role in ischemic cell death, a prerequisite of
      which is the development of increased excitability or an enhanced excitatory
      transmission in the selectively vulnerable subfields of the hippocampus. Such
      changes may take place upon the loss or malfunction of local inhibitory neurons
      in the early postischemic period. In the present study we examined the
      vulnerability of non-pyramidal neurons containing a recently discovered calcium
      binding protein, calretinin, in the rat hippocampus following 15 min ischemia
      induced by four-vessel occlusion. Immunostaining for calretinin enabled us to
      visualize a new type of spiny non-pyramidal cell in the hippocampus specifically
      associated with the mossy fiber system. This cell type is present exclusively in
      regions where mossy fiber terminals occur, i.e. in the hilus of the dentate gyrus
      and in stratum lucidum of the CA3 subfield. A selective loss of immunoreactivity
      in these neurons was already observed at 12-24 h after ischemia, when the
      pyramidal cells in the CA1 region showed no signs of damage. At a survival time
      of two to three days, most if not all spiny calretinin-immunoreactive cells had
      disappeared from the hippocampus. Other types of calretinin-containing GABAergic
      neurons were also reduced in number, but only at a time when CA1 pyramidal cells
      also started to degenerate, i.e. two to three days after ischemia. We speculate
      that the early loss of spiny calretinin-containing cells, together with other non
      pyramidal cells associated with the mossy fiber system (somatostatin-containing
      neurons and mossy cells of the hilus), may result in pathological network
      activity in the hippocampus, which may ultimately lead to an increased excitatory
      transmission and delayed pyramidal cell death in the CA1 region.

PMID- 8255423
TI  - Prolonged increases in neurotrophic activity associated with kainate-induced
      hippocampal synaptic reorganization.
AB  - Synaptic reorganization occurs in the hippocampus following various forms of
      seizure activity and injury, and may contribute to epileptogenesis. To address
      the hypothesis that neurotrophic factors play an inductive role in synaptic
      reorganization following seizures, we directly measured neurotrophic activity in
      rat hippocampal extracts after kainate injection or prolonged stimulation of the
      perforant path. Serial dilutions of hippocampal extracts were added to cultures
      of chick dorsal root ganglia, which are known to require trophic support from
      nerve growth factor and other neurotrophins, or ciliary ganglia neurons, which
      require trophic support from ciliary neurotrophic factor. Neurotrophic activity
      was significantly increased in hippocampal extracts harvested from 12 h to 2
      months after kainate treatment, with the peak effect seen at seven days. This
      neurotrophic activity was substantially blocked by an anti-nerve growth factor
      antibody. Extracts at seven days also showed a significant increase in ciliary
      neurotrophic factor-like activity. Sulfide/silver histochemistry, which stains
      dentate granule cell axon terminals, revealed that mossy fiber sprouting was
      evident two weeks following kainate treatment and increased progressively over
      the next two to six weeks. Perforant path stimulation that produced
      hyperexcitability in the dentate gyrus, but no sprouting, failed to induce
      changes in neurotrophic activity. These results suggest there are significant
      increases in neurotrophic factors following kainate-induced seizures, and the
      increases may be related to kainate-induced hippocampal injury rather than
      seizures per se. Furthermore, the timecourse of increased neurotrophic activity
      parallels that of mossy fiber reorganization, and is consistent with the
      hypothesis that neurotrophic factors play a role in the injury-induced synaptic
      reorganization seen in epilepsy.

PMID- 8255424
TI  - The cerebellum as a predictor of neural messages--I. The stable estimator
      hypothesis.
AB  - To describe how the central nervous system combines sensory messages, the
      hypothesis of a "stable estimator" is proposed: the central nervous system would
      construct internal estimates of the physical variables characterizing the body
      movements (e.g. head rotational velocity in space), while a regulating circuit
      would optimize the process of estimation of each variable, according to the
      available information and the overall performances of the sensorimotor reactions.
      The stable estimator of each variable would be embedded in a definite folium of
      the cerebellar cortex and the related cerebellar and brainstem nuclei. It would
      be controlled by the related part of the inferior olive. The estimate of each
      physical variable would be constructed by complementing the message from a
      dedicated sensory system (e.g. the semi-circular canals, which measure head
      rotational velocity in space) by neural messages related to the same variable
      (e.g. eye velocity in the head and retinal slip). Thus, the estimate would be
      accurate over the widest possible physiological ranges of frequency and velocity.
      The complementing signals would result from combining estimates of other
      variables (such as gaze velocity and eye velocity in the orbit), according to
      rules reproducing the relationships between physical variables. From the same
      complementing signals, the message from the dedicated sensory system would be
      predicted, and it is argued that this predictive function resides in the
      cerebellar cortex. The inferior olive would compare an actual signal about the
      performance of a sensorimotor reaction to signals of expected performance,
      computed from the various internal estimates of the variables which determine
      this performance. Any erroneous setting in a stable estimator would cause
      differences between the actual and the expected values. Then the inferior olive
      would compute an error signal directing compensatory functional plasticity.
      Finally, the whole estimating circuit would be regulated so that the internal
      coherence between neural messages and the performance of sensorimotor reactions
      would be achieved. Anatomical identifications and rules of functional plasticity
      are proposed.

PMID- 8255425
TI  - The cerebellum as a predictor of neural messages--II. Role in motor control and
      motion sickness.
AB  - The hypothesis of a "stable estimator" was proposed in the preceding article as a
      circuit computing an internal estimate of a body movement variable and endowed
      with regulating properties. Such a circuit would exist for each variable, and
      would be embedded in a particular folium of the cerebellar cortex and the related
      paths of the brainstem nuclei and the inferior olive. In this article, the action
      of the premotor orders on the stable estimator circuit is studied, at initiation
      and during execution of voluntary movements. A feedback loop via the cerebellar
      cortex would control on-going movements and maintain the efficacy of the
      stabilizing sensorimotor reaction, while preventing its interfering with the
      movement. The regulating loop via the inferior olive would have a short-term role
      in initiating movements and would boost insufficient stabilizing reactions. The
      discrepancy between internal estimates of the same variable would be reflected in
      motion sickness.

PMID- 8255426
TI  - Effects of chronic alcohol consumption and of dehydration on the supraoptic
      nucleus of adult male and female rats.
AB  - Ethanol ingestion affects the hypothalamo-neurohypophysial system resulting in
      increased diuresis, dehydration and hyperosmolality. We studied the supraoptic
      nucleus, of the hypothalamus, in ethanol-treated rats, to determine if ethanol
      alone and/or the associated disturbances of water metabolism lead to structural
      alterations in a nucleus known to play a central role in fluid homeostasis.
      Groups of male and female rats were ethanol-treated until 12 and 18 months of age
      and compared with age-matched pair-fed controls. Twelve and 18-month-old control
      groups and 12-month-old water control groups (rats submitted to chronic
      dehydration) were also included in this study in an attempt to differentiate
      between the effects of undernutrition and dehydration/hyperosmolality, and the
      specific neurotoxic effects of ethanol. We estimated the volume of the supraoptic
      nucleus and the numerical density of its neurons and calculated the total number
      of supraoptic neurons. The volume of both supraoptic neurons and neuropil were
      also estimated. In immunostained material the ratio of vasopressin to oxytocin
      neurons and the cross-sectional areas of the two neuronal types were evaluated.
      There was marked neuronal loss in alcohol-treated rats, but the volume of the
      supraoptic nucleus was increased. The increase in the volume of the supraoptic
      nucleus correlated with and was due to increases in the volume was particularly
      marked for vasopressin neurons. No significant differences were found between
      controls and pair-fed controls in any of the parameters investigated. In water
      control rats, the volume of the supraoptic nucleus and of the supraoptic neurons
      and neuropil was also greater than in pair-fed controls. However, the variations
      found were not as marked as in ethanol-treated rats and there was no cell loss.
      These findings reveal, for the first time, that chronic ethanol consumption
      affects the morphology of supraoptic neurons and neuropil and, consequently, the
      structure of the entire supraoptic nucleus. Moreover, this study supports the
      view that ethanol has direct neurotoxic effects on supraoptic neurons because the
      alterations that occur are not mimicked in animals in which water metabolism
      alone is disturbed.

PMID- 8255427
TI  - Effect of 5,7-dihydroxytryptamine lesion on mianserin-induced conditioned place
      aversion and on 5-hydroxytryptamine1C receptors in the rat brain.
AB  - The lesion of serotonergic neurons (by an intraventricular injection of 5,7
      dihydroxytryptamine) potentiated the conditioned place aversion induced by the 5
      hydroxytryptamine1C/5-hydroxytryptamine2 antagonist mianserin in rats. This
      effect was selective for mianserin as the same lesion suppressed the conditioned
      place aversion induced by the benzodiazepine inverse agonist FG-7142. Previous
      results had shown the involvement of the 5-hydroxytryptamine1C receptors in the
      conditioned place aversion induced by mianserin [Rocha et al. (1993) Behav.
      Pharmac. 4, 101-106]. It was thus of interest to investigate the effect of the
      lesion on these receptor binding sites. Autoradiographic binding studies showed
      that the lesion significantly increased the concentration of the 5
      hydroxytryptamine1C binding sites in various brain regions, including the
      amygdala, the hippocampus and the nucleus accumbens. Contrastingly, in these same
      brain regions, in situ hybridization histochemistry did not reveal an alteration
      of the level of messenger RNA coding for these receptors. On the one hand,
      correlating potentiation of the aversive effects of mianserin and increase of 5
      hydroxytryptamine1C binding sites in the limbic system represent an interesting
      step in the comprehension of the molecular and motivational effects of
      serotonergic drugs. On the other hand, showing a dissociation between the
      expression of 5-hydroxytryptamine1C receptors and their corresponding messenger
      RNA, suggest that post-transcriptional mechanisms are involved in the regulation
      of these receptors.

PMID- 8255428
TI  - Anticonvulsant agents, dizocilpine maleate, enadoline and HA 966 have different
      effects on N-methyl-DL-aspartate-induced immediate early gene induction in mice.
AB  - Administration of N-methyl-DL-aspartate (85 mg/ml) was given by infusion (0.14
      ml/min) until a clonic seizure was elicited. In situ hybridization was used to
      assess regional levels of four immediate early gene messenger RNA levels (c-fos,
      c-jun, junB, and a nerve growth factor induced gene, NGFI-A). Messenger RNA
      levels were highest at 25 min following infusion of N-methyl-DL-aspartate. c-jun
      messenger RNA levels remained elevated for over 2 h; however, c-fos, junB and,
      NGFI-A messenger RNA levels had returned to control levels by this time.
      Expression was detected in the hippocampus, hypothalamus and piriform cortex. Pre
      treatment (30 min prior to N-methyl-DL-aspartate) with the anticonvulsant drugs
      dizocilpine maleate (1 mg/kg) and HA 966 (200 micrograms, i.c.v.) resulted in
      significantly reduced immediate early gene messenger RNA levels in the
      hypothalamus and piriform cortex, and attenuated levels in the hippocampus. Pre
      treatment with the anticonvulsant agent enadoline (3 mg/kg), given at an
      anticonvulsant dose, did not result in reduced immediate early gene messenger RNA
      levels. These results suggest that monitoring immediate early gene expression may
      lead to advances in the understanding of the mechanism of action of many
      pharmacological agents, such as the kappa-opioid agonist enadoline.

PMID- 8255429
TI  - Effect of pentylentetrazol-induced seizures on A1 adenosine receptor regional
      density in the mouse brain: a quantitative autoradiographic study.
AB  - Adenosine has been shown to be a major regulator of neuronal activity in
      convulsive disorders, exerting its anticonvulsant effect through central A1
      adenosine receptors. The aim of the present study was to investigate the effect
      of generalized tonic-clonic seizures induced by pentylentetrazol on regional
      changes in A1 adenosine receptor density and distribution in the mouse brain by
      in vitro quantitative autoradiography. As radioligand the specific agonist of A1
      receptors [3H]cyclohexyladenosine was used. After two consecutive (once daily)
      pentylentetrazol-induced convulsions a widespread upregulation of A1 receptor
      density was detected with a marked enhancement in structures that mediate seizure
      activity like hippocampus, mamillary bodies, septum, substantia nigra, thalamic
      nuclei and cerebral cortices. On the contrary, in basal ganglia a significant
      downregulation of A1 receptors was observed. These results indicate that: (i) the
      observed increases or decreases in A1 receptor density are organized in selective
      anatomical structures related to seizure development rather than uniform in the
      brain; and (ii) since the upregulation of A1 receptors is sufficient to enhance
      the physiological depressive response of adenosine, the overall evoked increases
      seen here may lead to a stronger inhibitory tone and accordingly to a more
      efficient anticonvulsant effect of endogenous adenosine.

PMID- 8255430
TI  - Correlations between immediate early gene induction and the persistence of long
      term potentiation.
AB  - The duration of long-term potentiation in the dentate gyrus of awake rats was
      examined following systematic manipulation of the number of stimulus trains
      delivered. This was correlated with the induction of immediate early genes in
      separate groups of animals given identical stimulus regimes. Following 10 trains
      of stimulation, long-term potentiation decayed with a time constant of up to
      several days (long-term potentiation 2), and this correlated with the appearance
      of an increase in the messenger RNA and protein levels of zif/268. Increasing the
      number of stimulus trains resulted in a greater probability of eliciting long
      term potentiation with a time constant of several weeks (long-term potentiation
      3), as well as increasing the induction of zif/268, c-Jun, Jun-B, Jun-D and Fos
      related proteins. When 10 trains were delivered repeatedly on up to five
      consecutive days, only the zif/268 protein levels showed associated changes.
      These data provide support for the hypothesis that long-term potentiation 3
      involves mechanisms additional to those for long-term potentiation 2. One
      possible mechanism is altered gene expression, initiated by immediate early gene
      transcription factors such as zif/268 and possibly homo- or heterodimers of Fos
      and Jun family members, that then contributes to the stabilization or maintenance
      of long-term potentiation 3.

PMID- 8255431
TI  - The regional distribution of extracellularly regulated kinase-1 and -2 messenger
      RNA in the adult rat central nervous system.
AB  - It has previously been shown that an intracellular serine/threonine kinase known
      as extracellularly signal-regulated kinase, also known as microtubule-associated
      protein kinase, is phosphorylated and activated in response to a range of
      hormones, growth factors (e.g. nerve growth factor) and neurotransmitters (e.g. N
      methyl-D-aspartate) in a variety of cells including neurons. Extracellularly
      regulated kinases phosphorylate transcription factors, cytoskeletal proteins and
      enzyme targets. As such they are believed to function in neuronal signal
      transduction. In situ hybridization histochemistry using synthetic
      oligonucleotide probes has been used to identify cells in the adult rat central
      nervous system containing messenger RNAs coding for two isoforms of
      extracellularly regulated kinase. Extracellularly regulated kinase-2 messenger
      RNA was observed in many regions including the cerebral cortex, olfactory bulb,
      hippocampus, amygdala, basal ganglia (except the globus pallidus and
      endopeduncular nucleus), basal nucleus, thalamus, hypothalamus, brain stem
      nuclei, cerebellum and neurons in the spinal cord. Extracellularly regulated
      kinase-1 messenger RNA was confined to fewer regions than extracellularly
      regulated kinase-2 messenger RNA. Hybridization signals for extracellularly
      regulated kinase-1 were seen in the olfactory bulb, cortex, regions of the
      hippocampus, amygdala, nucleus basalis of Maynert, substantia nigra, some
      hypothalamic and brainstem nuclei and cerebellum, as well as neurons of the
      spinal cord. Of particular interest, extracellularly regulated kinase-1 messenger
      RNA was absent from all regions of the basal ganglia and thalamus. Furthermore,
      extracellularly regulated kinase-1 was almost absent from the CA1 region, whereas
      extracellularly regulated kinase-2 was present in all neurons of the hippocampus.
      There were no CNS regions that expressed extracellularly regulated kinase-1 but
      not extracellularly regulated kinase-2; however, neurons of the dorsal root
      ganglia showed extracellularly regulated kinase-1 but not extracellularly
      regulated kinase-2 messenger RNA. Although extracellularly regulated kinase-1 and
      extracellularly regulated kinase-2 expression was selectively neuronal in the
      brain, extracellularly regulated kinase-1 messenger RNA was localized to glia in
      the spinal cord. The distinct cellular distribution of individual extracellularly
      regulated kinases in the adult rat CNS suggests that they play unique signalling
      roles.

PMID- 8255432
TI  - Characterization of potassium currents in adult rat sensory neurons and
      modulation by opioids and cyclic AMP.
AB  - Using the whole-cell patch-clamp technique on acutely dissociated and cultured
      adult rat sensory neurons, we characterized the K+ currents by voltage
      dependence, kinetics, calcium dependence, and pharmacology. In the presence of Ca
      channel blockers, the cells heterogeneously expressed transient and sustained
      outward K+ currents. The transient current was a high-threshold A-current which
      activated at potentials greater than -30 mV and was blocked by 4-aminopyridine.
      Some of the sustained current was classified as a delayed rectifier. It
      demonstrated shallow voltage-dependent inactivation and was blocked by
      tetraethylammonium. Capsaicin produced large reductions in both transient and
      sustained currents with an EC50 of 8 microM. Likewise, dendrotoxin partially
      blocked both currents but with an EC50 of 21 nM. In the absence of Ca channel
      blockers, a prominent Ca-dependent K+ current was observed. The kinetics of whole
      cell potassium currents varied widely among cells, perhaps reflecting the
      different functional properties of sensory neurons. We also investigated the
      effects of elevating intracellular cyclic AMP and applying opioids on K+
      currents. Membrane-permanent analogs of cyclic AMP and phosphodiesterase
      inhibitors caused small reductions in voltage-dependent outward current. In
      contrast, forskolin produced a large reduction in outward current. This response
      was not solely mediated by cyclic AMP, since large responses were elicited with
      an inactive congener, 1,9-dideoxyforskolin, but not with the active, water
      soluble congener, 7-deacetyl-6-[N-acetylglycyl]-forskolin. Surprisingly, opioids
      had no effect on resting or voltage-dependent K+ conductances. However, opioid
      inhibition of Ca2+ currents and Ca-dependent K+ currents was observed. The
      failure to demonstrate opioid modulation of resting or voltage dependent K+
      currents suggests that modulation of Ca2+ currents is the principal mechanism for
      the inhibitory effect of opioids on sensory neurons.

PMID- 8255433
TI  - Training-induced increases in neuronal activity recorded from the forebrain of
      the day-old chick are time dependent.
AB  - Spontaneous neuronal bursting occurs in many areas of chick forebrain. Day-old
      chicks trained using a one-trial task to avoid a methylanthranilate-coated bead
      (methyl-chicks) show a significant increase in bursting when compared to chicks
      trained to peck a water-coated bead (water-chicks). This increase occurs in two
      forebrain areas: the intermediate medial hyperstriatum ventrale and the lobus
      parolfactorius. Bursting was recorded from the intermediate medial hyperstriatum
      ventrale of anaesthetized methyl- and water-chicks at eight time-points over the
      period 1-9 h post-test. Data merged over this period showed that methyl-chicks
      displayed an overall increase in bursting in both left and right hemispheres when
      compared to water-chicks. When burst activity was compared against time, bursting
      in methyl-chicks was significantly elevated only during the period 3-7 h post
      test. Maximal bursting in methyl-chicks was seen 6-7 h post-test. These results
      suggest that the training-induced increase in bursting seen in the intermediate
      medial hyperstriatum ventrale of methyl-chicks is not a simple, generalized
      increase with time but rather has a significant temporal aspect. These results
      may have particular relevance to previously proposed models of memory formation
      in the chick.

PMID- 8255434
TI  - Expression of highly polysialylated neural cell adhesion molecule in calcitonin
      producing cells.
AB  - Calcitonin-producing cells are endocrine derivatives of the neural crest and have
      several neuron-like properties. Expression of the neural cell adhesion molecule
      in calcitonin-producing cells was examined using two types of antibodies to
      neural cell adhesion molecule: monoclonal antibody 12E3 recognizes the polysialic
      acid portion of highly polysialylated neural cell adhesion molecule, and
      monoclonal antibody AF11 and polyclonal antiserum react with the polypeptide
      portion common to three major isoforms of neural cell adhesion molecule. An
      immunohistochemical study revealed that highly polysialylated neural cell
      adhesion molecule was expressed both in fetal rat thyroidal calcitonin-producing
      cells and in a calcitonin-producing cell line, rMTC 6-23, established from
      explantable neoplasm of rat calcitonin-producing cells. The neural cell adhesion
      molecule in the rMTC 6-23 cells was further characterized by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis and immunoblot analysis. Two anti
      neural cell adhesion molecule monoclonal antibodies, 12E3 and AF11, revealed a
      broad positive band around 200,000-250,000 mol. wt in solubilized proteins. When
      the polysialic acids were eliminated by neuraminidase treatment, the
      immunoreactivity to monoclonal antibody 12E3 was completely abolished, and core
      polypeptide corresponding to neural cell adhesion molecule with a molecular
      weight of 120,000 was detected by monoclonal antibody AF11. These results suggest
      that cells of the calcitonin-producing cell line express on their surfaces highly
      polysialylated 120,000 mol. wt form of neural cell adhesion molecule polypeptide.

PMID- 8255435
TI  - Bioequivalency revisited: epitol versus tegretol.

PMID- 8255436
TI  - Monitoring clinical trials.

PMID- 8255437
TI  - Fourth nerve palsy: historical review and study of 215 inpatients.
AB  - A review of inpatient trochlear nerve pareses diagnosed over 23 years revealed
      head trauma as the principal cause, with surgical injury, inflammation, and brain
      tumors seen occasionally. Ischemic (microvascular) neuropathies were rare. About
      one-half of the patients (52%) had no other neuro-ophthalmologic signs, but only
      5% were truly isolated, without other neurologic or ophthalmologic signs or
      symptoms. Fourth nerve palsies are underdiagnosed on hospital services, where
      stuporous patients encounter unsuspecting physicians.

PMID- 8255438
TI  - Driving and Alzheimer's disease: the risk of crashes.
AB  - We designed this questionnaire-based study to determine the risk of auto crashes
      among Alzheimer's disease (AD) patients who continued to drive after the onset of
      AD, compared with normal age-matched control subjects and other drivers'
      statistical records. While ultimately all AD patients will become incapable of
      driving, it is not known whether, under current licensing regulations and self
      imposed limitations, patients with AD present a definably increased risk of being
      involved in crashes, and if so, the relative magnitude of the risk and at what
      point in the course of the disease the risk may become significantly increased.
      We administered a brief questionnaire to the caregivers of 130 AD patients and to
      112 age-matched, nondemented control subjects and their spouses. Annual rates of
      occurrence and severity of all crashes, and of crashes reported to the
      authorities, were determined from spousal or other caregiver responses. For all
      years of driving following the onset of dementia, AD patients had a mean of 0.091
      reported crashes per year compared with matched controls, who had an average of
      0.040 reported crashes per year in the same period of time. The average number of
      crashes per year changed with each year of driving following the onset of AD,
      with considerably lower reported crash rates during the initial years of
      dementia: in year 1, the crash rate was 0.068; in year 2, 0.097; in year 3,
      0.093; in year 4, 0.159; in year 5 and beyond, 0.129.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8255439
TI  - The consortium to establish a registry for Alzheimer's disease (CERAD). Part IV.
      Rates of cognitive change in the longitudinal assessment of probable Alzheimer's
      disease.
AB  - Reliable information on rate of progression of cognitive impairment in probable
      Alzheimer's disease (AD) is important for evaluating possible beneficial effects
      of therapeutic agents and in planning long-term care for patients with this
      chronic illness. However, wide variability exists in published rates of change
      for psychometric measures of the dementing process, and there is need for an
      accurate analysis of large numbers of persons with the disorder studied over long
      periods. Utilizing the large, well-characterized sample of the Consortium to
      Establish a Registry for Alzheimer's Disease and employing a least squares
      regression method to adjust for different levels of impairment and periods of
      observation, we report rates of change on the Short Blessed Test, Mini-Mental
      State Examination, Blessed Dementia Scale, Clinical Dementia Rating, and other
      cognitive measures in 430 patients with probable AD (mean age at entry = 70.9 +/-
      8.0 SD years) studied for up to 4 years. We found that rate-of-change
      determinations are less reliable when the observation period is 1 year or less,
      that dementia progression may be nonlinear when described by certain measures,
      and that simple change scores do not accurately characterize the rate of decline.
      We also found that rate of progression in AD is determined by the severity of
      cognitive impairment: the less severe the dementia, the slower the rate of
      decline.

PMID- 8255440
TI  - Branched-chain amino acids and amyotrophic lateral sclerosis: a treatment
      failure? The Italian ALS Study Group.
AB  - We initiated a double-blind, placebo-controlled trial to test the efficacy and
      safety of branched-chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 6 g,
      and L-valine 6 g daily) in amyotrophic lateral sclerosis (ALS) patients. There
      was an excess mortality in subjects randomized to active treatment (24 BCAA, 13
      placebo) when a total of 126 ALS patients had been recruited. This finding,
      associated with the lack of efficacy of BCAA (measured by comparing the
      disability scales in the two treatment groups), led the Data Monitoring Committee
      to require cessation of the trial.

PMID- 8255441
TI  - MELAS syndrome masquerading as herpes simplex encephalitis.
AB  - Herpes simplex encephalitis (HSE) is commonly treated empirically with acyclovir
      without confirmatory brain biopsy. Three consecutive adults with molecularly
      verified mitochondrial encephalomyopathy, lactic acidosis, and stroke-like
      episodes (MELAS) syndrome presented with, and were treated for, apparent HSE.
      MELAS syndrome in adults may present as an atypical, recurrent form of HSE and
      should be added to the list of neurologic diseases that can mimic HSE.

PMID- 8255442
TI  - Migraine and migrainous stroke: risk factors and prognosis.
AB  - We compared epidemiologic and clinical data from 310 patients with migraine and
      30 patients with acute migrainous stroke to identify factors predictive of
      migrainous stroke and assess the risk of future stroke in these two populations.
      We found no significant differences in gender ratio or in the frequency of
      smoking, estrogen use, hypertension, mitral valve prolapse, or family history of
      migraine between the two groups. A history of migraine with aura was
      significantly more common in the migrainous stroke group (24 of 30 [80%] versus
      142 of 310 [46%]; p < 0.001), as was a history of prior stroke (nine of 30 [30%]
      versus four of 310 [1.3%]; p < 0.001). We followed 173 of the migraine patients
      for at least 1 year and a mean of 35.8 months, and no strokes occurred in this
      group. We followed 28 of the migrainous stroke patients for a mean of 25.3
      months, and there were six recurrent strokes in that group, all again migraine
      associated. Migrainous stroke is more common in individuals with aura than in
      those who are aura-free, but this association is of little value in attempting to
      distinguish patients destined for migrainous stroke from the migraine population
      at large. Patients with a history of migraine-associated stroke are at
      significantly increased risk for recurrent stroke.

PMID- 8255443
TI  - Migraine-related seizures in adults with epilepsy, with EEG correlation.
AB  - We studied the relationship between migraine and epilepsy in 395 adult seizure
      patients. Seventy-nine patients (20%) also had migraine syndrome, and 13 of these
      patients (3%) experienced seizures during or immediately following a migraine
      aura. Patients with catamenial epilepsy and patients with migraine with aura were
      at an increased risk for an association between these two disorders. In two
      patients, we recorded the entire sequence from migraine aura to partial seizure,
      and in both there were distinctive changes on the EEG during the migraine aura
      that preceded the onset of an electrographic complex partial seizure. Periodic
      lateralized epileptiform discharges were recorded in five other patients in close
      temporal relation to their migraine attacks. There was improved seizure control
      with combination antimigraine and antiepileptic drugs (AEDs) in six patients who
      failed to respond to AEDs alone.

PMID- 8255444
TI  - Proton MR spectroscopic characterization of differences in regional brain
      metabolic abnormalities in mitochondrial encephalomyopathies.
AB  - Localized brain proton MR spectra were acquired from patients with different
      mitochondrial encephalomyopathies (myoclonus epilepsy with ragged-red fibers
      [MERRF], Kearns-Sayre syndrome [KSS], and mitochondrial encephalomyopathy, lactic
      acidosis, and stroke-like episodes [MELAS]). The regional brain metabolic
      abnormalities in patients with these syndromes showed different features
      consistent with the distinct phenotypes. In MERRF, only one of four patients
      showed an increase in the lactate/creatine resonance intensity ratio (an index of
      impairment of oxidative metabolism) in spectra from central (supraventricular) or
      occipital brain volumes, and this was small. There were significant decreases in
      N-acetylaspartate/creatine (a measure of neuronal loss or dysfunction) in central
      cerebral volumes of demented patients and, more prominently, in occipital
      volumes. In the one patient in whom it was studied, the cerebellum also showed a
      decreased N-acetylaspartate/creatine. Spectra from two patients with KSS both
      showed large (four- to sevenfold) increases in lactate/creatine and large
      decreases in N-acetylaspartate/creatine in central brain volumes. Yet another
      pattern of regional metabolic abnormality was present in the MELAS syndrome,
      where proton spectroscopic imaging demonstrated focal localization of abnormally
      increased lactate/creatine and decreased N-acetylaspartate/creatine to the
      regions of the stroke-like lesions on conventional MR images. Serial studies
      emphasized that the regional metabolic abnormalities in MELAS are highly variable
      as the stroke-like lesions appear and evolve.

PMID- 8255445
TI  - Neuropsychologic correlates of MRI white matter hyperintensities: a study of 150
      normal volunteers.
AB  - To determine the effects of MRI white matter hyperintensities (WMH) on cognitive
      functioning, we used neuropsychologic tests and MRI to study 150 elderly
      volunteers free of neuropsychiatric or general disease. There were 76 (50.3%)
      individuals without and 74 (49.7%) with WMH. The latter subset was older (61.3 +/
      6.6 years versus 58.5 +/- 5.8 years, p = 0.005), had a higher mean arterial
      blood pressure (103.7 +/- 11.4 mm Hg versus 99.9 +/- 10.3 mm Hg, p = 0.03), and a
      larger ventricular-to-intracranial-cavity ratio (6.3 +/- 5.6% versus 4.7 +/-
      1.6%, p = 0.02). Individuals with WMH performed worse than their counterparts
      without such abnormalities on all tests administered. After adjusting for the
      group differences in age, arterial blood pressure, and ventricular size, we noted
      statistically significant results on form B of the Trail Making Test (121.8 +/-
      37.8 msec versus 100.3 +/- 47.9 msec, p = 0.04), a complex reaction time task
      (680.8 +/- 104.9 msec versus 607.1 +/- 93.9 msec, p = 0.001), and the assembly
      procedure of the Purdue Peg-board Test (27.5 +/- 5.8 versus 30.6 +/- 5.9, p =
      0.02). Partial correlations did not reveal any relationship between test scores
      and the semiautomatically assessed total area of WMH. Our data suggest that the
      presence of WMH exerts a subtle effect on neuropsychologic performance of normal
      elderly individuals, which becomes particularly evident on tasks measuring the
      speed of more complex mental processing.

PMID- 8255446
TI  - Parkinson's disease and somatosensory evoked potentials: apomorphine-induced
      transient potentiation of frontal components.
AB  - We recorded somatosensory evoked potentials (SEPs) to median nerve stimulation
      from parietal and frontal districts in 32 patients with Parkinson's disease by
      evaluating latency/amplitude characteristics of the parietal P14-N20-P25 and of
      the frontal P20-N30-P40 wave complexes before and 10, 20, 30, and 60 minutes
      after subcutaneous administration of apomorphine chloride. The frontal complex
      N30-P40 was smaller than normal in 17 patients in baseline recordings. Following
      apomorphine, the parietal responses did not significantly vary in amplitude, but
      the frontal complex showed a remarkable amplitude potentiation in 22 of 32
      patients (68.7%, p < 0.001), 19 of whom were also improving clinically. Amplitude
      potentiation was evident 10 minutes after apomorphine and faded away nearly in
      parallel with the end of its clinical efficacy. There were no SEP changes in
      three healthy controls after apomorphine.

PMID- 8255447
TI  - Evaluation of the effects of vigabatrin on cognitive abilities and quality of
      life in epilepsy.
AB  - We evaluated the psychological effects of the antiepilepsy drug vigabatrin in a
      randomized multicenter double-blind placebo-controlled parallel group study that
      compared 3 grams oral vigabatrin with placebo as daily add-on therapy in patients
      with focal epilepsy whose complex partial seizures were difficult to control.
      Testing at baseline and after 12 weeks of vigabatrin (n = 83) or placebo (n = 85)
      used eight measures of cognitive abilities and three of mood and adjustment. The
      vigabatrin and placebo groups were highly similar at entry into the study. At the
      end of the study, there were no differences between the vigabatrin and placebo
      groups on any cognitive variable or on any measure of mood and adjustment.
      Analysis of the results related to relief from seizures demonstrated only chance
      findings. In a similar manner, there were no relationships between vigabatrin
      serum levels at the end of the study and changes on measures of abilities and
      adjustment. Vigabatrin appears to be a useful antiepilepsy drug with little
      impact upon tests of either cognitive abilities or quality of life.

PMID- 8255448
TI  - Neurophysiologic and clinical correlations of epileptic nystagmus.
AB  - Epileptic nystagmus (EN) is a rare sign of seizure activity. We describe eight
      patients with horizontal EN and hypothesize that the frequency of ictal
      discharge, anatomic localization of ictal activity, and level of consciousness
      determine its occurrence and mechanism. We believe that EN is due to epileptic
      activation of a cortical saccade region; in each case, quick phases were
      generated away from the side of the focus, and both quick and slow phases were
      totally confined to the field contraversive to the seizure focus.

PMID- 8255449
TI  - Twin birth is not a risk factor for seizures.
AB  - There is a belief that perinatal factors are a major cause of epilepsy. We
      studied a community-based sample of twins, a group with a marked excess of
      adverse perinatal events. The observed number of non-twin siblings with seizures
      did not differ from that predicted by the age-specific cumulative incidence rate
      of seizures (4.2% at age 10 years) in the twins. The types of epilepsies in the
      twins were largely benign and self-limited and not those associated with brain
      damage. Zygosity, birth order, and birth weight did not predict affected status.
      Within affected sibships, the frequency of seizures in co-twins of dizygotic
      probands (9%) was not different from the frequency in non-twin siblings (12%) but
      was much less than the frequency in co-twins of monozygotic probands (38%; p <
      0.001), reflecting a major genetic component to certain epilepsies. These data
      show that twins do not have an increased risk of seizures and strongly suggest
      that perinatal factors have little bearing on the etiology of the common
      epilepsies in the community.

PMID- 8255450
TI  - Lateralizing signs in intractable partial epilepsy: blinded multiple-observer
      analysis.
AB  - We evaluated the accuracy and interobserver variability of selected ictal and
      postictal behavioral changes. Three observers, blinded to clinical history, EEG,
      and side of surgical resection, analyzed videotapes of 166 seizures in 38
      patients, looking for lateralizing signs. Twenty-seven patients with temporal
      lobe resections were seizure-free for > or = 1 year postoperatively, and 11 with
      extratemporal resections had at least 90% reduction in seizures > or = 1 year
      postsurgery. The epileptogenic region (ER) was lateralized by analyzing
      lateralizing signs in 78% of patients; positive predictive value (PPV) was 94%
      (90% CI = 87% to 100%). Overall kappa was 0.68. Signs were considered present if
      seen by two or more observers. Forty-five percent had version, ie, forced and
      sustained head deviation (kappa = 0.76, PPV = 94%); 37% had dystonic posturing of
      the upper extremity (kappa = 0.47, PPV = 93%); and 34% had unilateral mouth
      deviation (kappa = 0.83, PPV = 92%). These signs indicated a contralateral ER.
      Twenty-one percent had unilateral upper extremity automatisms, all ipsilateral to
      the ER (kappa = 0.65, PPV = 100%); 21% had postictal dysnomia, indicating a
      dominant-hemisphere ER (kappa = 0.89, PPV = 100%); and 16% had ictal speech,
      usually indicating a nondominant-hemisphere ER (kappa = 0.75, PPV = 83%).
      Dystonic posturing, postictal dysnomia, ictal speech, and unilateral upper
      extremity automatisms may indicate a higher probability of temporal lobe
      epilepsy. Analysis of lateralizing signs shows good interobserver agreement and
      provides useful clinical information.

PMID- 8255451
TI  - Reliability of seizure classification using a semistructured interview.
AB  - Methods for standardized classification of epileptic seizures are important for
      both clinical practice and epidemiologic research. In this study, we developed a
      strategy for standardized classification using a semistructured telephone
      interview and operational diagnostic criteria. We interviewed 1,957 adults with
      epilepsy ascertained from voluntary organizations. To confirm and expand the
      seizure history, we also interviewed a first-degree relative for 67% of subjects
      and obtained medical records for 59%. Three lay reviewers used all available
      information to classify seizures. To assess reliability, each reviewer classified
      a sample of subjects assigned to the others. In addition, an expert physician
      classified a sample of subjects assigned to two of the reviewers. Agreement was
      "moderate-substantial" for generalized-onset seizures, both for the comparisons
      between pairs of lay reviewers and for the neurologist versus lay reviewers.
      Agreement was "substantial-almost perfect" for partial-onset seizures, both for
      pairs of lay reviewers and for the neurologist versus lay reviewers. These
      results suggest that seizures can be reliably classified by lay reviewers, using
      operational criteria applied to symptoms ascertained in a semistructured
      telephone interview.

PMID- 8255452
TI  - Seizure localization in temporal lobe epilepsy: a comparison of scalp-sphenoidal
      EEG and volumetric MRI.
AB  - We determined the accuracy of volumetric MRI (based on identification of
      unilateral hippocampal atrophy) and scalp-sphenoidal EEG (based on concordant
      interpretations of scalp-sphenoidal ictal EEG by three independent interpreters)
      for seizure focus localization in 20 patients with temporal lobe epilepsy. All
      patients became seizure-free or had rare seizures following temporal lobectomy.
      Among the 20 patients, nine (45%) met both MRI and EEG localization criteria, six
      (30%) met MRI localization criteria alone, three (15%) met EEG localization
      criteria alone, and two patients (10%) did not meet either localization criteria.
      In the 18 patients meeting MRI or EEG localization criteria, the predicted
      localization agreed with the side of temporal lobectomy. These results suggest
      that a noninvasive approach combining MRI and EEG will correctly localize the
      side of seizure onset in most patients with temporal lobe epilepsy.

PMID- 8255453
TI  - Intravenous glucose after out-of-hospital cardiopulmonary arrest: a community
      based randomized trial.
AB  - QUESTION: Does the common practice of infusing small amounts of glucose after
      cardiopulmonary arrest worsen neurologic outcome? DESIGN AND SETTING: A community
      based randomized trial in Seattle, WA. Paramedics treated all patients with out
      of-hospital cardiac arrest in a standard fashion except that the intravenous
      infusion did or did not contain glucose; ie, patients received either usual
      treatment, with 5% dextrose in water (D5W), or alternative, with half normal
      saline (0.45S). OUTCOMES: The main outcome was awakening, defined as the patient
      having comprehensible speech or following commands as determined by chart review.
      Other outcomes were survival to hospital admission and to discharge. RESULTS:
      Over 2 years, paramedics randomized 748 patients. The type of fluid administered
      was not significantly related to awakening (16.7% for D5W versus 14.6% for
      0.45S), admission (38.0% for D5W versus 39.8% for 0.45S), or discharge (15.1% for
      D5W versus 13.3% for 0.45S). As in previous studies, patients whose arrest had
      likely been on a cardiac basis with initial rhythms of ventricular fibrillation
      or asystole had admission blood glucose levels significantly related to
      awakening: mean = 309 mg/dl for never awakening and 251 mg/dl for awakening. Of
      note, the relation between glucose and awakening was reversed in the remaining
      patients, who had electromechanical dissociation or noncardiac mechanisms of
      arrest. CONCLUSION: Current practices of using limited amounts of glucose
      containing solutions after cardiopulmonary arrest do not need to be changed.
      Blood glucose level on admission is a prognostic indicator but depends on the
      type of arrest.

PMID- 8255454
TI  - Horizontal semicircular canal variant of benign positional vertigo.
AB  - We report the clinical features and results of quantitative eye-movement testing
      in 13 patients with episodic positional vertigo and nonfatiguing direction
      changing horizontal positional nystagmus (beating to the right with the head
      turned to the right and beating to the left with the head turned to the left).
      The benign history and lack of associated neurologic findings support a
      peripheral localization of the lesion. This syndrome probably represents a
      horizontal semicircular canal variant of benign positional vertigo. Free-floating
      debris in one horizontal canal may explain many of the clinical and oculographic
      findings.

PMID- 8255455
TI  - Lumbosacral radiculoplexopathy as a manifestation of Epstein-Barr virus
      infection.
AB  - We report the clinical features of five patients with lumbosacral
      radiculoplexopathy (LSRP) and one patient with a femoral neuropathy, all of whom
      had serologic evidence of a recent Epstein-Barr virus (EBV) infection. After a
      thorough investigation, no other etiology was apparent. Pain was a prominent
      feature in all cases, and the prognosis was generally good, with recovery in
      weeks to months. We conclude that LSRP may occur as a postinfectious process
      following recent EBV infection.

PMID- 8255456
TI  - Strokes in children due to vertebral artery trauma.
AB  - Strokes due to vertebral artery lesions are rare in children. We describe three
      new patients and compare them with the 16 other patients described in the
      literature. All of these patients are boys. Traumatic vertebral artery lesion at
      C1-2 level was the most common cause of stroke, and the prognosis for neurologic
      recovery was good. We suggest that vertebral artery disease be considered in boys
      with posterior circulation ischemia.

PMID- 8255457
TI  - Intermediate nerve conduction velocities define X-linked Charcot-Marie-Tooth
      neuropathy families.
AB  - Three genetic loci for the Charcot-Marie-Tooth (CMT) syndromes with slow motor
      nerve conduction velocities (hereditary motor and sensory neuropathy: HMSN type
      I) have been mapped to chromosomes 1 (CMT1B), 17 (CMT1A), and the X chromosome
      (CMTX). The clinical features of these three CMT subgroups are similar. To
      determine whether any clinical features distinguish CMTX families, the range of
      clinical findings and motor nerve conduction velocities were examined in two
      large CMTX families, the range of clinical findings and motor nerve conduction
      velocities were examined in two large CMTX families with CMTX proven by linkage
      to X-chromosome markers. CMTX males had more wasting and weakness than CMTX
      females or individuals with CMT1A. Patellar reflexes were more often retained in
      CMTX. Motor nerve conduction velocities were faster than in CMT1A. Intermediate
      range median nerve conduction velocities were present in CMTX females (45 +/- 9
      m/sec; range, 26 to 61 m/sec). These velocities were significantly faster than
      those for CMT1A females (22 +/- 8 m/sec, p < 0.0001). Median nerve conduction
      velocities in CMTX males (31 +/- 6 m/sec) were significantly slower than in CMTX
      females and faster than in CMT1A males (20 +/- 6 m/sec, p < 0.0001). The
      combination of slow conduction velocities in affected males (< 40 m/sec) and
      intermediate-range median motor conduction velocity results (> 40 m/sec) in
      affected or obligate carrier females is a useful distinguishing feature to
      separate CMTX from CMT1A, as intermediate conduction velocities are not present
      in autosomal-dominant dominant CMT1A families. This feature defines possible CMTX
      families for linkage studies. Families with no male-to-male inheritance of the
      syndrome, slow motor nerve conductions in affected males, and normal or
      intermediate-range conduction velocities in carrier females should be considered
      to be X-linked CMT families.

PMID- 8255458
TI  - [18F]FDG PET in fatal familial insomnia: the functional effects of thalamic
      lesions.
AB  - We used [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission
      tomography (PET) to study regional cerebral glucose utilization (rCMRglc) in four
      patients with fatal familial insomnia (FFI), a prion disease with a mutation at
      codon 178 of the prion protein gene. Two patients, presenting only with insomnia
      and dysautonomia, had a prominent and, in one case, selective thalamic
      hypometabolism. The remaining two cases presented a more complex clinical picture
      with multiple neurologic deficits, with both thalamic and widespread brain
      hypometabolism involving the majority of cortical structures, basal ganglia, and
      the cerebellum. This widespread pattern was present in the early stage of the
      disease and showed significant worsening as the disease progressed in one patient
      examined twice. The thalamic hypometabolism, consistently found with PET in FFI
      patients, is in agreement with the neuropathologic findings and is a hallmark of
      the disease.

PMID- 8255459
TI  - MRI pallidal hyperintensity and brain atrophy in cirrhotic patients: two
      different MRI patterns of clinical deterioration?
AB  - In cirrhotic patients, even in a stable nonencephalopathic state, MRI may show
      cerebral atrophy and increased signal in globus pallidus on T1-weighted
      sequences. We investigated the relationship between cerebral atrophy and
      increased pallidal signal and the clinical status of 30 cirrhotic patients. We
      found a weak association between the two MRI findings. There were different
      patterns of clinical variables related to the imaging findings. Performance on
      motor tasks involving speed correlated with the pallidal signal and plasma
      ammonia levels but not with atrophy. Test results for memory and frontal-premotor
      function were associated with brain atrophy but not with the pallidal signal or
      with ammonia.

PMID- 8255460
TI  - Antineuronal antibodies in patients with neurologic complications of primary
      Sjogren's syndrome.
AB  - Neurologic complications of both the central and peripheral nervous systems occur
      frequently in patients with primary Sjogren's syndrome (primary SS), but the
      underlying cause of these complications is unknown. We studied the presence of
      antineuronal antibodies in relation to neurologic complications in a consecutive
      series of 45 patients with primary SS. Twenty-five patients had neurologic
      complications: 12 patients with polyneuropathy, three with psychiatric disorders,
      four with carpal tunnel syndrome, seven with migraine, seven with myalgia, and
      four with other complications (transverse myelitis, stroke, Bell's palsy, and
      pyramidal signs). Ten patients had more than one neurologic complication. Eleven
      patients had major and 14 had minor complications according to criteria used for
      rating neurologic complications in patients with systemic lupus erythematosus.
      Antineuronal antibodies were present in six of 11 (55%) patients with major
      neurologic complications and in four of 34 (11%) of patients without major
      neurologic complications (p = 0.001). This difference could be attributed mainly
      to the group of patients with polyneuropathy. Three of the 10 sera of patients
      with positive antineuronal antibodies had antibodies reacting with a 38-kd
      neuronal protein on immunoblotting, identical to the anti-Hu antibody reactivity
      in paraneoplastic neurologic disease associated with small-cell lung cancer.

PMID- 8255461
TI  - Cytosol protein kinase C downregulation in fibroblasts from Alzheimer's disease
      patients.
AB  - We attempted to determine whether changes in protein kinase C (PKC) activity in
      Alzheimer's disease (AD) brains are also present in cultured skin fibroblasts
      from living patients. Biopsies collected from shoulder skin were transferred to
      culture plates with an appropriate growth medium, and histone-directed PKC
      activity as well as phorbol ester binding were individually determined in soluble
      and particulate fractions prepared from AD and non-AD fibroblast cell lines.
      Binding experiments indicated that PKC was unevenly distributed between cytosol
      (78%) and particulate (22%). The Bmax values for phorbol ester binding in soluble
      and particulate fractions were similar in AD and non-AD patients. Kd values in
      the cytosol were 94% higher in AD patients, indicating lower affinity of the
      enzyme for the ligand. Accordingly, the soluble PKC activity was 30% lower in AD
      patients. The data suggest that the changes in PKC phosphorylating activity
      represent a diffuse cellular defect in AD and are not confined to the brain. The
      alterations of the enzyme may participate in the disregulation in processing of
      beta-amyloid precursor protein in AD.

PMID- 8255462
TI  - Novel brainstem syndrome associated with prostate carcinoma.
AB  - Two patients successfully treated for prostatic cancer developed a progressive
      neurologic syndrome beginning with loss of voluntary horizontal eye movements
      followed by severe, persistent muscle spasms of the face, jaw, and pharynx. Both
      had mild gait unsteadiness, and one exhibited facial and abdominal myoclonus.
      Extensive diagnostic studies, including MRIs of the brainstem (with and without
      contrast), were normal. CSF examination showed mild pleocytosis and elevated IgG.
      Quantitative eye movement recordings documented selective involvement of
      voluntary horizontal saccades with sparing of horizontal slow eye movements.
      Neither patient had antineuronal antibodies in the blood. Postmortem examination
      revealed perivascular chronic inflammatory cells and microglial infiltration of
      the pons and medulla. One patient also had perivascular infiltrates in both
      mesial temporal lobes. Neuronal loss was localized to the pontine tegmentum, the
      medullary sensory nuclei, and the cerebellum. Brainstem motor nuclei were
      preserved. The clinical and pathologic findings suggest an autoimmune process
      (probably paraneoplastic) with selective damage to a subpopulation of brainstem
      neurons critical for horizontal eye movements and recurrent inhibition of bulbar
      nuclei.

PMID- 8255463
TI  - Rapid-onset dystonia-parkinsonism.
AB  - We studied a large family with a previously undescribed, autosomal dominant
      dystonia-parkinsonism syndrome. We chose to call the disorder "rapid-onset
      dystonia-parkinsonism" (RDP) based on the unusually rapid evolution of signs and
      symptoms. Affected individuals developed dystonia and parkinsonism between 14 and
      45 years of age. The onset was acute in six individuals with the abrupt onset of
      symptoms over the course of several hours, and subacute in four others who had
      evolution over several days or weeks. Thereafter, progression of symptoms was
      usually very slow. Two had intermittent focal dystonia without parkinsonism, and
      one obligate gene carrier was asymptomatic at 68 years. CSF levels of
      homovanillic acid were decreased in the two individuals tested, but dopaminergic
      therapy provided only slight benefit. The DYT1 gene responsible for early-onset,
      generalized idiopathic torsion dystonia in Jewish and some non-Jewish families
      has been mapped to chromosome 9q34. Linkage analysis with three markers near the
      DYT1 gene showed several obligate recombinations, excluding DYT1 as a candidate
      gene for RDP. We believe RDP is unique and should be classified separately from
      other forms of hereditary dystonia-parkinsonism.

PMID- 8255464
TI  - Communicating hydrocephalus, basilar invagination, and other neurologic features
      in osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is anecdotally associated with macrocephaly,
      hydrocephalus, basilar invagination, and cerebral atrophy, but the frequency and
      the spectrum of neurologic features of this condition are poorly defined. We
      report our experience with 76 patients with OI seen at NIH. Neuroimaging studies
      demonstrated sulcal prominence and ventriculomegaly consistent with communicating
      hydrocephalus in 17 patients. Eight individuals with severe OI types displayed
      basilar invagination, causing brainstem compression in three patients. Head
      circumference growth showed abnormal kinetics with percentile crossing after
      fontanelle closure in 13 patients, and absolute macrocephaly was present in 11
      patients. Additional neurologic complications included skull fracture (10
      individuals); seizure disorders (five); transient, unexplained long tract signs
      (three); and spinal compression and pontine, cervical, and thoracic
      syringohydromyelia (one patient each). The clinically important neurologic
      complications appear to be brainstem compression from basilar invagination, skull
      fracture, and seizure disorders. Neurologic evaluation should be part of a team
      approach in the management of patients with severe OI types.

PMID- 8255466
TI  - Facilitation of magnetic motor evoked potentials during the cortical stimulation
      silent period.
AB  - We investigated the relationship between stimulus intensity and magnetic motor
      evoked potentials (MEPs) elicited 100 msec after a conditioning stimulus that was
      25% of stimulator output above resting motor threshold (RMT) during tonic
      contraction of abductor pollicis brevis. In five subjects, MEPs elicited with
      stimuli less than 25% above RMT were inhibited during the EMG cortical
      stimulation silent period (CSSP) produced by the conditioning stimulus, relative
      to MEPs elicited with the test stimulus given at rest. However, increasing the
      intensity of the test stimulus increased the amplitude of MEPs elicited during
      the CSSP relative to MEPs elicited at rest, such that MEPs elicited with stimuli
      30 to 45% above RMT were facilitated during the CSSP. Increasing the intensity of
      the test stimulus also increased the amplitude of MEPs elicited with paired
      stimulation at rest, and caused facilitation in one subject. Since facilitation
      of MEPs was never accompanied by shortening of MEP latency, our observations
      point to supraspinal facilitory mechanisms. We suggest that facilitation of MEPs
      during the CSSP reflects temporal and spatial summation of conditioning and test
      stimuli.

PMID- 8255465
TI  - Neurologic manifestations in children with North American Lyme disease.
AB  - To delineate the spectrum of neurologic manifestations and the relative
      frequencies of different syndromes associated with North American Lyme disease,
      we describe 96 children referred for neurologic problems in the setting of
      Borrelia burgdorferi infection. The most frequent neurologic symptom was
      headache, and the most common sign was facial palsy. Less common manifestations
      were sleep disturbance, and papilledema associated with increased intracranial
      pressure. Signs and symptoms of peripheral nervous system involvement were
      infrequent. The most common clinical syndromes were mild encephalopathy,
      lymphocytic meningitis, and cranial neuropathy (facial nerve palsy). In contrast
      with adult patients with neurologic Lyme disease, meningoradiculitis (Bannwarth's
      syndrome) and peripheral neuropathy syndromes were rare. However, a "pseudotumor
      cerebri-like" syndrome seems to be unique to North American pediatric Lyme
      disease.

PMID- 8255467
TI  - Spinal cord MRI using multi-array coils and fast spin echo. I. Technical aspects
      and findings in healthy adults.
AB  - It is time-consuming to detect intrinsic spinal cord lesions in multiple
      sclerosis (MS) by MRI using conventional surface coils and T2-weighted spin-echo
      pulse sequences. Multi-array coils and fast spin-echo pulse sequences permit the
      generation of high-resolution T2-weighted sagittal images of the whole spinal
      cord in about 5 minutes. Using these advances, we found an area of high signal
      within the cord in only 1/45 (2%) healthy subjects aged 18 to 72 years, whereas
      26% of those who underwent brain imaging had cerebral white matter abnormalities.
      Degenerative vertebral column changes, especially in the cervical region, were
      present in 64% and were associated with cord compression in 11%. Cord cross
      sectional areas in mm2, measured from axial gradient-echo images, were usually
      highly reproducible and showed a significant correlation with the subject's
      height. We conclude that (1) MRI signal abnormalities within the spinal cord may
      be more specific for MS than cerebral white matter lesions, especially in
      subjects over 50 years old; (2) asymptomatic degenerative changes in the
      vertebral column are common, even in younger adults; (3) measurement of cord
      cross-sectional area should allow accurate quantitation of the degree of atrophy
      in MS and other spinal cord diseases; and (4) multi-array coils and fast spin
      echo represent an important advance in MRI of the spinal cord.

PMID- 8255468
TI  - Spinal cord MRI using multi-array coils and fast spin echo. II. Findings in
      multiple sclerosis.
AB  - We performed MRI of brain and spinal cord on 80 patients with multiple sclerosis
      (MS). Using multi-array coils and fast spin echo, 139 intrinsic lesions were
      identified in 59 patients (74%). Lesions were more common in the cervical than in
      the thoracic cord. Cross-sectional areas of the cord, measured from axial images
      at four levels, showed atrophy in 40%. Clinical disability correlated with cord
      atrophy but not with cord lesion load. These results show that the use of multi
      array coils and fast spin echo allows rapid and sensitive detection of spinal
      cord lesions in MS and that the cord is involved in the majority of patients. A
      lack of association between cord lesions and disability may relate to limitations
      in MR resolution but also suggests that the mechanisms of disability in MS are
      complex and multifactorial.

PMID- 8255469
TI  - Dissociable cognitive and neural mechanisms of unilateral visual neglect.
AB  - We administered two experimental tasks to 16 patients with neglect following
      unilateral right hemisphere strokes, designed to probe processing of information
      in the neglected left visual field. A semantic priming/lexical decision task
      examined implicit processing of stimuli presented to the neglected field, and a
      discrimination task required explicit recognition of the same stimuli. We grouped
      patients according to three patterns of performance: (1) poor discrimination in
      the left visual field but intact priming, (2) normal priming and discrimination
      in both fields, and (3) normal priming but poor discrimination in both fields.
      Although patients in group 1 had posterior lesions, patients in groups 2 and 3
      had extensive deep anterior lesions. These results suggest that the clinical
      phenomenon of unilateral visual neglect can be the surface manifestation of
      deficits in two different and interacting processes--attentional processes (group
      1) and intentional processes (group 2)--or it may be a global attentional
      disturbance superimposed on these deficits (group 3).

PMID- 8255471
TI  - The effect of nicotine on recurrent inhibition in the spinal cord.
AB  - Recurrent inhibition via Renshaw cells provides a mechanism by which spinal and
      supraspinal centers exert control over movement. The conditioned H-reflex
      technique of Pierrot-Deseilligny and Bussel permits noninvasive assessment of
      recurrent inhibitory pathways. We employed this technique to investigate changes
      in Renshaw cell activity due to nicotine (a potent CNS cholinergic agonist that
      excites Renshaw cells in animals) contained in inhaled tobacco smoke. In 10
      normal subjects, cigarette smoking caused a large, rapid drop in the conditioned
      H-response amplitude, implying increased activation of Renshaw cells. The time
      course of the change in conditioned H-response amplitude closely approximated the
      known pharmacokinetics of inhaled nicotine. Nicotine administered via chewing gum
      had a much slower and less dramatic effect, probably due to the slower rise in
      blood levels with this mode of administration. Increased activity in Renshaw
      cells may contribute to spasticity in spinal cord-injured patients, raising the
      possibility that cigarette smoking could cause further increases in tone in such
      patients.

PMID- 8255470
TI  - Serum folate and chronic fatigue syndrome.
AB  - We assayed serum folate levels of 60 patients with chronic fatigue syndrome (CFS)
      and found that 50% had values below 3.0 micrograms/l. Some patients with CFS are
      deficient in folic acid.

PMID- 8255472
TI  - Exclusion of mutations in the gene for type III collagen (COL3A1) as a common
      cause of intracranial aneurysms or cervical artery dissections: results from
      sequence analysis of the coding sequences of type III collagen from 55 unrelated
      patients.
AB  - We performed detailed DNA sequencing analysis on type III collagen cDNA from 58
      patients with either intracranial artery aneurysms or cervical artery
      dissections. The 58 patients were of seven different nationalities; among the
      patients were three pairs of relatives, so that 55 were unrelated, and of these,
      29 had at least one blood relative with either an intracranial artery aneurysm or
      a cervical artery dissection. The age of the patients at the time of diagnosis
      ranged from 15 to 68 years (mean +/- SD = 40.3 +/- 11.0). The study group
      consisted of 25 males and 33 females. The analysis covered 3,232 nucleotides of
      significant (nonredundant) sequences per allele; therefore, we analyzed as many
      as 355,520 nucleotides. Mutations in the coding sequences for the triple-helical
      domain of type III collagen were excluded in 40 individuals with intracranial
      aneurysms and 18 individuals with cervical artery dissections. Direct sequencing
      of polymerase chain reaction products allowed mutations to be excluded with a
      high degree of confidence. Mutations that markedly decreased expression from one
      allele were also excluded in 42 of the 58 individuals, since the presence of both
      bases at one or more polymorphic sites in the 42 patients showed that two alleles
      were transcribed. The results indicated that mutations in the gene for type III
      procollagen (COL3A1) are not a common cause of either intracranial artery
      aneurysms or cervical artery dissections.

PMID- 8255473
TI  - Uniform slowing of conduction velocities in Charcot-Marie-Tooth polyneuropathy
      type 1.
AB  - We evaluated motor conduction studies in 129 patients with Charcot-Marie-Tooth
      disease type 1 (CMT1) to assess the uniformity of conduction slowing within
      individual patients. Conduction velocities were nearly identical in proximal and
      distal nerve segments (r = 0.86), from side to side (r = 0.95), in ipsilateral
      median and ulnar nerves (r = 0.94), and even in the median and peroneal nerves (r
      = 0.70). Segmental amplitude reductions suggestive of possible conduction block
      or differential dispersion were present in only 19 of 360 nerve segments studied
      (5.3%), and interphase cancellation or focal compression were likely alternative
      explanations in these cases. These findings support the concept that uniform
      conduction slowing characterizes CMT1, in distinction to acquired demyelinating
      polyneuropathies, which feature multifocal conduction abnormalities. We conclude
      that normal nerve conduction velocity in a single motor nerve can reliably
      exclude CMT1, but evaluation of several nerves and nerve segments to establish
      uniformity of conduction slowing is important in making this diagnosis. The
      homogeneity of the disturbance of nerve conduction favors a primary Schwann-cell
      disorder as the basis of CMT1.

PMID- 8255475
TI  - Somatic instability of CTG repeat in myotonic dystrophy.
AB  - An unstable expansion of the CTG repeat in the 3' untranslated region of the
      myotonin protein kinase (MT-PK) gene is the mutation specific for myotonic
      dystrophy (DM). To examine somatic stability of the repeat, we studied tissue
      variability of the repeat size. In five DM patients, the restriction fragment
      containing the repeat region was substantially larger in skeletal muscle than in
      peripheral blood leukocytes (PBL). In addition, one normal subject showed a size
      discrepancy in one of the normal alleles by one repeat on the polymerase chain
      reaction analysis. In most DM patients, the repeat size of native PBL differed
      from the transformed lymphoblastoid cells after passages. In contrast, various
      tissues from a congenital DM patient showed a similar size of the expanded
      repeat, including the transformed lymphoblastoid cells. We conclude that somatic
      instability of the CTG repeat may cause substantial tissue variability of the CTG
      repeat size in adult-onset DM, providing a potential mechanism for the variable
      pleiotropism.

PMID- 8255474
TI  - Nerve growth factor reverses neuronal atrophy in a Down syndrome model of age
      related neurodegeneration.
AB  - Atrophy and dysfunction of certain neurons, including cholinergic neurons in the
      basal forebrain, are key features of the neuropathology of Alzheimer's disease
      (AD). Since all individuals with Down syndrome (DS) develop AD neuropathology by
      the 4th decade, we reasoned that a genetic model of DS, the trisomy 16 (Ts 16)
      mouse, may provide an animal model to study the neurodegeneration in AD. Ts 16
      mice fail to survive birth; to evaluate neurons for long periods in vivo required
      transplantation of fetal tissue. We previously demonstrated that Ts 16 basal
      forebrain cholinergic neurons (BFCNs) undergo age-related atrophy similar to DS
      and AD, and now show that a specific neurotrophic factor, nerve growth factor
      (NGF), acts to reverse Ts 16-induced atrophy of BFCNs and stimulates hypertrophy
      of these cells. As NGF levels were not decreased in the host, abnormalities
      intrinsic to Ts 16 BFCNs presumably caused the atrophy. Our results suggest that
      NGF may be useful in reversing cholinergic neurodegeneration in DS and AD.

PMID- 8255476
TI  - Increased levels of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis
      factor receptor in the cerebrospinal fluid of patients with multiple sclerosis.
AB  - We investigated the presence of soluble intercellular adhesion molecule-1 (sICAM
      1) and soluble tumor necrosis factor receptor (sTNF-R) antigens in the CSF of
      patients with multiple sclerosis (MS) using a double-determinant ELISA. Patients
      with acute relapsing MS during an exacerbation (p < 0.001) and those with chronic
      progressive MS (p < 0.001) had significantly increased CSF levels of sICAM-1
      compared with subjects with other neurologic diseases. CSF levels of sTNF-R were
      also significantly increased in patients with acute relapsing MS during an
      exacerbation (p < 0.001) and chronic progressive MS (p < 0.001) compared with
      subjects with other neurologic diseases. CSF levels of sICAM-1 and sTNF-R were
      positively correlated in patients with acute relapsing MS during an exacerbation
      (r = 0.81, p < 0.01) and chronic progressive MS (r = 0.86, p < 0.001). These
      results suggest that active immune reactions involving ICAM-1 and TNF-R
      production are present within the CNS and that both sICAM-1 and sTNF-R are
      important immunologic markers of the clinical activity of MS.

PMID- 8255477
TI  - Coital cerebral hemorrhage.
AB  - Sudden headache, confusion, and hemiparesis followed within minutes of late
      morning sexual intercourse in a 39-year-old man. Imaging studies revealed
      hemorrhage into a vascular malformation. Sexual intercourse and circadian rhythm
      independently elevate blood pressure, and their concurrence may predispose to
      cerebral hemorrhage in the presence of a vascular malformation.

PMID- 8255478
TI  - Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa
      action in parkinsonian patients.
AB  - The wearing-off phenomenon frequently complicates levodopa therapy of Parkinson's
      disease (PD). These response fluctuations appear when intrasynaptic dopamine
      concentrations begin to reflect the swings in levodopa availability that attend
      standard dosing regimens. Drugs that prolong the biologic half-life of levodopa
      and dopamine should thus prove beneficial. We administered levodopa/carbidopa in
      combination with single oral doses of tolcapone (Ro 40-7592), an inhibitor of
      catechol-O-methyltransferase, under controlled conditions to 10 PD patients with
      the wearing-off phenomenon. Tolcapone prolonged the antiparkinson response to
      levodopa/carbidopa by about 67% at several doses ranging from 50 to 400 mg (p <
      0.05). There was no significant change in the peak levodopa effect on
      parkinsonian signs or in the severity of dyskinesias. No dose-limiting adverse
      effects occurred. Multiple daily dosing with tolcapone would thus be expected to
      safely reduce the wearing-off phenomenon associated with levodopa/carbidopa
      therapy.

PMID- 8255479
TI  - Evidence for impairment of energy metabolism in vivo in Huntington's disease
      using localized 1H NMR spectroscopy.
AB  - The Huntington's disease (HD) gene mutation has recently been found; however, the
      biochemical defect that leads to neurodegeneration is still unknown. A
      progressive impairment of neuronal energy metabolism is a possible etiologic
      factor. We tested this possibility using localized proton nuclear magnetic
      resonance (NMR) spectroscopy in 18 patients at high risk for, or suffering from,
      HD as compared with normal controls. Lactate concentrations were increased in the
      occipital cortex of symptomatic HD patients when compared with normal controls,
      and the lactate level correlated with duration of illness. In addition, several
      patients showed highly elevated lactate levels in the basal ganglia. Basal
      ganglia levels of N-acetylaspartate were lowered and choline dramatically
      elevated, relative to creatine, reflecting neuronal loss and gliosis in this
      brain region. These findings are consistent with a possible defect in energy
      metabolism in HD, which could contribute to the pathogenesis of the disease. The
      presence of elevated lactate in HD brains may provide a simple marker that can be
      followed over time noninvasively and repeatedly to aid in devising and monitoring
      possible therapies for HD patients.

PMID- 8255480
TI  - Carbamazepine toxicity resulting from generic substitution.
AB  - Generic substitution is practiced widely in both hospital and community settings.
      There have been several reports of reduced serum concentrations and seizure
      exacerbation following generic substitution of Tegretol. We describe the first 2
      cases of carbamazepine toxicity resulting from the substitution of Tegretol with
      Epitol. Two 6-year-old children experienced increases in the maximum serum
      carbamazepine concentration, one of 22% and one of 41%. Both became asymptomatic
      when their serum concentrations were lowered and had no residual effects.

PMID- 8255481
TI  - Pathologic changes associated with intracranial hypotension and meningeal
      enhancement on MRI.
AB  - We report a patient with a 6-week history of postural headache due to
      intracranial hypotension whose MRI revealed findings typical of this syndrome,
      including diffuse meningeal enhancement following gadolinium infusion. Biopsy
      revealed extensive fibrocollagenous proliferation in the leptomeninges without
      evidence of inflammation. The pathologic changes in this patient, which occurred
      soon after the onset of symptoms, are probably related to the striking meningeal
      enhancement seen in this syndrome.

PMID- 8255482
TI  - Ifosfamide causes a diazepam-sensitive encephalopathy.
AB  - An encephalopathy characterized by confusion, stupor, and mutism frequently
      occurs during administration of the chemotherapeutic drug ifosfamide (IFX). We
      investigated two patients who developed encephalopathy during IFX infusion. Both
      exhibited a rapid and near-complete restoration of baseline mental status
      functioning concurrent with EEG improvement after administration of intravenous
      diazepam. We recommend an EEG and trial of benzodiazepines in patients with IFX
      encephalopathy.

PMID- 8255483
TI  - Sudden hearing loss as the initial monosymptom of multiple sclerosis.
AB  - Hearing loss is an uncommon symptom in multiple sclerosis. We report two patients
      in whom unilateral sudden hearing loss was the first monosymptomatic
      manifestation of multiple sclerosis. We confirmed the initial central auditory
      dysfunction suggested by audiometric findings and brainstem auditory evoked
      potentials by MRI, which showed a unilateral pontine lesion in one patient and a
      lesion in the medulla oblongata in the other.

PMID- 8255484
TI  - Stroke due to Lyme disease.
AB  - A 56-year-old Connecticut woman suffered multiple strokes 18 months after
      antibiotic treatment for early Lyme disease with facial palsy. Pleocytosis,
      intrathecal synthesis of anti-Borrelia burgdorferi antibody, and the response to
      antibiotic treatment substantiated the diagnosis of neuroborreliosis. This is the
      first report of stroke caused by Lyme disease acquired in North America.

PMID- 8255485
TI  - A case of cerebral endometriosis causing catamenial epilepsy.
AB  - We present the second reported patient with cerebral endometriosis. She had
      repetitive partial seizures on the first day of her menstrual cycle. The seizures
      were controlled by danazol after the causative lesions were surgically removed.

PMID- 8255486
TI  - How many alien hand syndromes? Follow-up of a case.
AB  - We report the follow-up of a patient affected by a persistent alien left
      nondominant hand. CT and MRI showed an ischemic lesion localized to the mesial
      frontal region and involving the supplementary motor area and anterior fibers of
      the corpus callosum. These findings support theories suggesting a critical role
      of both these lesions in determining "chronic" forms of alien hand of either
      upper limb.

PMID- 8255487
TI  - Q fever mimicking herpetic encephalitis.
AB  - We describe a patient with temporal lobe encephalitis associated with primary
      Coxiella burnetii infection who presented with CT and MRI findings suggestive of
      herpes simplex encephalitis and an initial improvement during treatment with
      acyclovir. Q fever should be considered in the differential diagnosis of patients
      whose manifestations suggest herpes encephalitis.

PMID- 8255488
TI  - Spontaneous calcific embolization to the supraclinoid internal carotid artery
      from a regurgitant bicuspid aortic valve.
AB  - Calcific brain embolization leading to stroke is rarely recognized. We report a
      case of spontaneous embolization to the right cerebral circulation from a
      severely regurgitant, calcified bicuspid valve. Bicuspid aortic valves constitute
      the most common congenital heart abnormality, and have a tendency to become
      stenosed, regurgitant, calcified, or infected. The presence of heavy
      calcification in a noninfected bicuspid valve may lead to dislodgement of
      calcific embolic material which is not necessarily heralded by acute valvular
      rupture. Accurate localization of the calcific embolus to the right supraclinoid
      internal carotid artery was provided by spiral CT imaging in this case.

PMID- 8255489
TI  - Association of the 11778 mitochondrial DNA mutation and demyelinating disease.
AB  - Leber's hereditary optic neuropathy is a maternally inherited disorder most
      commonly associated with a mitochondrial DNA mutation at nucleotide position
      11778. We report four patients, including a man and a black woman, with the 11778
      mutation, who have optic neuropathy and clinical or paraclinical evidence of
      demyelinating disease. These data support an association of this mitochondrial
      DNA mutation with demyelinating disease that has a marked female predominance.

PMID- 8255490
TI  - Combination therapy for PD.

PMID- 8255491
TI  - Combination therapy for PD.

PMID- 8255493
TI  - Selegiline.

PMID- 8255492
TI  - Immunoglobulin therapy.

PMID- 8255494
TI  - Controlled-release levodopa.

PMID- 8255495
TI  - Intravenous immunoglobulin versus plasma exchange in Guillain-Barre syndrome.

PMID- 8255496
TI  - Intravenous immunoglobulin versus plasma exchange in Guillain-Barre syndrome.

PMID- 8255497
TI  - Treatment of optic neuritis.

PMID- 8255498
TI  - [The role of the Vabra aspirator in the screening of endometrial carcinoma. Our
      experience].
AB  - The aim of study was to estimate the utility of Vabra aspirator in the screening
      of endometrial carcinoma. For this and 656 patients aged over 40 were subjected
      to cytologic examination and we compared the date obtained with the histologic
      examination, when the woman was subjected to surgical operation. The research
      which we carried out was of the retrospective type and it lasted two years. The
      patients were recruited at the division out-clinic and locally. All the
      examinations were carried out at the division, using the method of Vabra
      aspirator with the Kit of Sterilab. The patients admitted to examination showed
      some menstrual anomalies, (spotting, abnormal uterine bleeding, metrorrhagias and
      after postmenopausal uterine bleeding), and stayed at our USSL or at neighbouring
      ones. The cytologic examination have been read beside a single centre and the
      cytologic diagnosis has been compared with the histology one on the operating
      organ. The result obtained agrees with the literature. In fact, out of 888
      screened women, 656 were aged over 40 and 232 aged less than 40. In the group of
      656 patients 3 adenocarcinoma have been diagnosed and 4 atypical hyperplasia,
      equivalent to 0.33% and to 0.45% respectively. In conclusion, we can say that the
      method has shown a good diagnostic reliability into the diagnosis of malignant
      neoplasia. According to other authors, its limit is, instead, the high number of
      inadequate, besides the impossibility to diagnose other uterine pathologies, such
      as the endometrial polyps and the uterine myoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255499
TI  - [Prenatal screening for Down's syndrome: a simplified method].
AB  - Prenatal screening for Down's syndrome (DS) can be achieved by combining maternal
      age risks and maternal serum additional parameters (AFP, HCG, uE3) by computer
      assisted statistical analysis. Nevertheless this measure of risk is far from
      broad and practical application in Italy, due to cultural and organization
      difficulties. So we suggest a different technical approach, the age specific risk
      being multiplied by the HCG/AFP likelihood ratio. HCG and AFP can be tested by an
      automated Elisa assay, and calculations performed by a simple method, excluding
      computer and software package use. About 100 pregnancies were evaluated both by a
      modified version of the Wald test and the method described hereafter. Using the
      automated HCG and AFP Elisa Testing and Crossley statistical calculation a higher
      False Positive Rate was observed. On the other hand no different Detection Rate
      was observed for the two tests. On a retrospective study we found that 5 sera
      from affected pregnancies were correctly identified both by the modified Wald
      test and the other method. It is concluded that, despite different False Positive
      Rates, the choice of which test to use depends on evaluation of local resources,
      one test being easier-to-perform and more sensitive, the other one probably being
      more specific but more difficult to perform.

PMID- 8255500
TI  - [Guidance for the obstetrician encountering a multiple pregnancy].
AB  - A retrospective review of multiple birth of higher order delivered at the
      Obstetric Clinic of University of Rome "La Sapienza" from 1982-1991 was
      performed. Comparison was made between this group (study group) and other
      published data. Since 1982 there has been more liberal use of abdominal delivery.
      Of the 25 multiple pregnancies, 17 were delivered by cesarean section (CS) and 8
      by vaginal delivery. The corrected mortality rate in the study group was 19.2%
      (5/26) for vaginal delivery and 17.5% (10/57) for CS. Indication for CS was:
      elective (35%), fetal (18%) and maternal (47%). The main neonatal complications
      resulted from prematurity, and maternal noted complication were post-partum
      hemorrhage necessitating hysterectomy in one patient. The preferable mode of
      delivery cannot be stated dogmatically.

PMID- 8255501
TI  - [Endometrial ablation. A review of the technics and results].
AB  - The authors make a careful examination of a very new surgical hysteroscopic
      technique, endometrial ablation, which is proposed as an alternative to
      hysterectomy in cases of persistent uterine bleeding not supported by endometrial
      atypia or adenocarcinoma. In addition to examining the indications for this type
      of surgery the authors also assess the state of the art of two techniques
      currently used: the laser technique and the method based on electroresection. The
      risks, benefits, collateral effects and results are evaluated for each method.

PMID- 8255502
TI  - [The selective embolization of the hypogastric arteries in the treatment of
      hemorrhages due to cervical carcinoma. The report of 2 clinical cases].
AB  - Transcatheter arterial embolization (TAE) has been reported to effectively
      control bleeding in the gynecological and obstetric field. We report the use of
      selective hypogastric arteries embolization in the management of severe
      persistent cervical bleeding in two patients affected by advanced cervical
      cancer. Bleeding stopped in both cases; no serious side-effects were noticed. In
      a short time hematological status was restored and both patients had a long
      bleeding-free time. We consider TAE the treatment of choice in controlling
      persistent neoplastic cervical bleeding. Indications, usefulness and
      complications of such a technique are herein discussed.

PMID- 8255503
TI  - [Giant-cell arteritis of the female genital tract].
AB  - One case of giant-cell arteritis involving the female genital tract of a post
      menopausal woman is reported. The patient was a 75 year-old female, who presented
      anemia, fatigue, weight loss and a palpable abdominal mass. A hysterectomy and
      bilateral salpingo-oophorectomy proved multiple uterine leiomyomas. The uterus,
      ovaries and tubes unexpectedly revealed extensive giant-cell arteritis of small
      and medium sized vessels. Giant-cell arteritis of the female genital tract is a
      rare finding that may occur as an isolated form or as part of generalized giant
      cell arteritis.

PMID- 8255504
TI  - [The hand-foot-uterus syndrome. A report of a case with recessive autosomal
      inheritance].
AB  - The authors report a new case of hand-foot-uterus syndrome, an infrequent and
      peculiar clinical condition characterized by skeletal anomalies of the
      extremities associated with alterations in the development of Mullerian
      derivation structures. The female patient in fact present morphological and
      skeletal anomalies to the extremities and a bicornate, twin-necked uterus with
      double vagina. This genetic condition is normally transmitted with a autosomal
      dominant pattern. The consanguinity of the parents and the absence of other like
      cases in the family led the authors to suppose that this is an even rarer form
      with a recessive autosomic-type inheritance. The importance of an accurate
      diagnosis is underlined not only to ensure better management, but above all for a
      more appropriate examination of their reproductivity.

PMID- 8255505
TI  - [The conservative treatment of placenta accreta. A clinical case report].
AB  - The following description is a clinical case of placenta accreta and its
      conservative treatment. According to some authors, abnormal adhesion of the
      placenta depends on the alteration of the equilibrium between the trophoblastic
      tissue invasion and the reaction of the decidua. Consequently we have various
      degrees of penetration of the myometrium by chorionic villi into areas of
      deficit, sparse or absent decidua. Whatever the pathogenetic mechanism, the final
      clinical picture is slight to deep penetration of the trophoblastic tissue into
      the uterine wall. That causes absence of the normal plane of cleavage between
      placenta and maternal decidua, no spontaneous placental detachment during the
      third stage of labour and no possible manual removal. The patient, primigravida,
      was admitted at the 36th Week of gestation with PROM and physiologically
      delivered a neonate weighing 1820 g, after she spontaneously began labour. The
      newborn was admitted in the neonatal-pathology ward because it was premature
      although the Apgar score at 1-5 minutes after birth was 5-9. Placental ejection
      was awaited for 1 hour, then manual exploration of the uterine cavity was
      undertaken. The normal plane of cleavage between placental tissue and decidua was
      absent and therefore manual extraction of the placenta was impossible. Surgery
      was stopped and, after informed consensus was obtained from the patient, a
      conservative treatment was tried. After cutting the umbilical cord as short as
      possible and checking for vaginal bleeding, the patient was moved to obstetrics
      ward.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255506
TI  - [Urinary calculi in an intestinal loop used for ureteral substitution. A case
      report].
AB  - The authors report the case of large urinary calculi formed inside the ileal
      conduit diversion in a patient who underwent radical surgery for an ovarian
      carcinoma involving the right ureter. Two ureter stents were left to ensure
      drainage and were endoscopically removed after six months. Renal function and
      ureteral canalization were normal. However, because of a knot in the proximal end
      of stents, a piece 5 cm-long-was left inside the diversion. After six months the
      patient developed recurrent renal colics: plain abdomen X-ray and urography
      showed a large urinary stone around the stents fragment and several smaller
      stones nearby. They all were removed surgically. The pathogenesis of such
      complications was considered: even though the slow flux of urine in the
      diversion, the abnormal mucus production from the ileal mucosa and the excessive
      and chronic bicarbonate loss played an important role in the developing of
      urinary calculi, the authors believe that in this case the main responsible for
      the stone formation was the foreign body in the urinary diversion.

PMID- 8255507
TI  - [Endometriosis of the large intestine. A report of 2 clinical cases].
AB  - Intestinal involvement of endometriosis requiring treatment is 5%, but only 0.7%
      needs intestinal resection. The authors report two cases of colic endometriosis
      and illustrate problems in diagnosis and management of this disease. Usually
      intestinal endometriosis takes the form of asymptomatic superficial serosal
      implants, encountered incidentally at laparotomy for other diseases, but it can
      also result in obstruction and occasionally bleeding. Any premenopausal woman
      with episodic bowel symptoms associated with gynecologic complaints should be
      suspected of endometriosis of the colon. Diagnosis can be suspected by double
      contrast enema examination and colonoscopy with biopsy, although neither is
      likely to establish the diagnosis with certainty. In fact there are no radiologic
      or diagnostic imaging findings that are specific for endometriosis and
      unequivocal diagnosis requires microscopic examination. Differential diagnosis
      includes primary carcinoma of the colon and other benign diseases (pelvic
      inflammatory disease, diverticulitis, inflammatory bowel disease, pelvic abscess,
      polyps, etc.). The treatment of patients with uncomplicated, but symptomatic
      gastrointestinal endometriosis depends on the age of the patient and her
      childbearing attitude. Resection of the affected bowel should be done in patient
      with pain, bleeding, changes in bowel habits and intestinal obstruction and it is
      necessary to avoid neglecting a malignant tumor. Total abdominal hysterectomy and
      bilateral oophorectomy is the treatment of choice in the perimenopausal and
      menopausal women. In symptomatic women desiring children the only resection of
      involved colon may be appropriate treatment. In these subjects hormonal therapy
      can be useful.

PMID- 8255508
TI  - [The induction of labor by using extra-amniotic intrauterine estrogens. Our
      experience].
AB  - Induction of labour using extra-amniotic intrauterine estrogens. Personal
      experience. The study was carried out in a series of 20 primagravidae in whom it
      was necessary to induce labour. The method used entailed the introduction, via an
      extra-amniotic transcervical route, of approximately 16 mg of estrogen paste.
      There is a full discussion of the technical details and results obtained which
      appear to be encouraging for the routine use of this method.

PMID- 8255509
TI  - Beta 2-microglobulin-derived amyloidosis: clinical use of scintigraphy and
      insights into its pathogenesis.

PMID- 8255510
TI  - Renal hypoperfusion as the primary cause of cyclosporin-induced nephropathy.

PMID- 8255511
TI  - Enhancement of screening tests for renovascular hypertension by angiotensin
      converting enzyme inhibition.

PMID- 8255512
TI  - Angiotensin-converting enzyme inhibition and the combination of a beta blocker
      and a diuretic are equally effective in lowering proteinuria in patients with
      glomerulonephritis.
AB  - In this study we compared the antihypertensive and antiproteinuric efficacies of
      an angiotensin-converting enzyme inhibitor and of conventional treatment
      consisting of a beta blocker and a diuretic in 13 patients with biopsy-proven
      glomerulonephritis and a proteinuria of more than 2 g/24 h. Ten of these 13
      patients were normotensive. None had diabetes mellitus. In a randomized cross
      over design with two treatment periods of 6 weeks, each preceded by a washout
      period of 4 weeks, patients were treated with benazepril (20 mg o.d.) and the
      combination of metoprolol (200 mg o.d.) and chlorthalidone (25 mg o.d.). At the
      end of the treatment periods with benazepril or metoprolol/chlorthalidone mean
      arterial pressure was lowered to a similar degree by 7.4 (mean, 95% confidence
      interval 2.0-12.7) and 9.7 (5.7-13.7) mmHg respectively. Both treatment
      modalities caused similar reductions in proteinuria, being 3.4 g/24 h (mean, 95%
      confidence interval 2.1-4.8) on benazepril and 3.2 (1.2-5.1) g/24 h on
      metoprolol/chlorthalidone. Glomerular filtration rate and renal plasma flow were
      slightly less during metoprolol/chlorthalidone treatment. Subgroup analysis of
      normotensive patients gave similar results. In conclusion, in these patients with
      glomerular disease angiotensin-converting enzyme inhibition was not more
      effective than the conventional treatment with the combination of a beta blocker
      and a diuretic in reducing blood pressure and proteinuria. Both treatments
      reduced proteinuria not only in hypertensive, but also in normotensive patients.

PMID- 8255513
TI  - Extracorporeal treatment of hypercholesterolaemia.
AB  - Extracorporeal removal of LDL cholesterol (LDL apheresis) has been carried out in
      patients with diet- and drug-resistant hypercholesterolaemia to prevent or to
      reduce coronary heart disease. Plasma separation is the first step in all five
      LDL-apheresis methods presently available. Plain plasma exchange and double
      membrane filtration are unselective and remove HDL cholesterol and plasma
      proteins. Adsorption of LDL to dextran sulphate, to LDL antibodies, or
      precipitation of LDL by heparin at low pH are more selective. With all methods
      LDL cholesterol reduction per treatment is 60-70%. In most patients one treatment
      per week is sufficient to reduce mean LDL to 100-150 mg/dl. Minor side-effects
      occur in 10 +/- 5% of treatments. Major side-effects are rare. Long-term LDL
      apheresis increased survival in patients with homozygous familial
      hypercholesterolaemia. In heterozygous familial hypercholesterolaemia controlled
      studies regarding survival are not available. Uncontrolled trials indicate
      regression of coronary artery disease in heterozygotes with drug- and diet
      resistant LDL cholesterol > 200 mg/dl. Hence, LDL apheresis is indicated in all
      patients with homozygous familial hypercholesterolaemia. LDL apheresis in
      heterozygous familial hypercholesterolaemia should be restricted to patients with
      diet- and drug-resistant LDL cholesterol > 200 mg/dl with coronary heart disease
      and/or other atherosclerotic vascular lesion.

PMID- 8255514
TI  - Tubulointerstitial nephritis and uveitis: association with suppressed cellular
      immunity.
AB  - It is suggested that tubulointerstitial nephritis and uveitis (TINU) is a cell
      mediated immune disease with a favourable response to treatment with steroids.
      However, long-term follow-up has not been described and data on immunological
      studies are limited. The aim of this study was to evaluate the clinical features
      in patients with TINU who have had a long follow-up period, and in parallel to
      assess their cellular immunity and HLA typing. Four women with TINU were followed
      for 5.7 +/- 3.6 years. On remission they were studied for T-cell-mediated
      immunity by skin tests, T-cell subpopulations, and lymphokine secretion in vitro.
      The lymphokines included interleukin-2, gamma-interferon, tumour necrosis factor,
      and colony-stimulating factor. The in vitro response to AS101, a previously
      described immunomodulator, was evaluated. HLA-typing was also performed. The
      nephritis, which occurred once, was resolved in all patients and did not recur.
      In contrast, numerous relapses of uveitis occurred despite topical or systemic
      steroid treatment. The patients' T-cell subpopulations did not differ from
      controls, but they revealed anergy to skin tests and a very low secretion rate of
      lymphokines. AS101 corrected the suppressed secretion in vitro. A high frequency
      of HLA-DR6 antigen was found in the TINU patients. TINU is probably a systemic
      disease with a chronic relapsing course of the uveitis but with complete clinical
      recovery of the nephritis. Both in vivo and in vitro T-cell functions are
      suppressed during remission.

PMID- 8255515
TI  - Acute renal failure in the elderly: experience from a single centre in India.
AB  - A total of 139 patients with acute renal failure (ARF) were studied, of which 41
      (29.4%) were elderly with mean age of 67.1 years and 98 (70.6%) were younger with
      mean age of 32.3 years. Surgical causes accounted for 65% of geriatric ARF while
      medical causes were predominant in the younger patients (55.1%). Amongst the
      surgical causes, prostate-related problems due to obstruction or following
      transurethral resection of prostate were seen in 20 patients (74%). Drugs and
      sepsis were the predominant causes of medical ARF in the geriatric patients
      (85.7%). Of all the causes of geriatric ARF, which included both medical and
      surgical, nephrotoxic drugs either alone or in combination with other
      predisposing factors were the cause in 22 (51%) patients. Haemodialysis was
      needed in 15 of geriatric (36.6%) and 64 of younger (65.3%) ARF patients.
      Recovery from ARF, as evidenced by normalization of serum creatinine, was delayed
      in the elderly as compared to the younger patients (32.0 versus 11.4 days, P <
      0.001). Mortality, though higher in the elderly as compared to the younger
      patients, was not significantly different (9.75% versus 6.1%).

PMID- 8255516
TI  - Plasma lipoproteins and renal apolipoproteins in rats with chronic adriamycin
      nephrosis.
AB  - The relation between plasma lipoprotein composition and renal apolipoprotein
      deposition was studied in nephrotic rats in which stable renal function had been
      monitored for 7 months after a single low dose of adriamycin (ADR, 3 mg/kg).
      Proteinuria was observed 3 weeks after ADR and increased progressively up to
      about 0.5 g/day (versus 0.07 g/day in controls; P < 0.001), while the creatinine
      clearance remained stable at about 80% of control values. Hypercholesterolaemia
      was observed 6 weeks after ADR, and increased progressively up to 7.0 +/- 1.0
      mmol/l (versus 2.3 +/- 0.1 mmol/l in controls; P < 0.001). Cholesterol was
      primarily located in LDL2 and HDL2 lipoproteins. Plasma apolipoprotein (apo) A-I
      increased by more than 400% in the nephrotic rats (P < 0.001). Apo B and apo E
      increased by about 60% (P < 0.01), whereas apo A-IV remained unchanged. Focal
      sclerotic lesions in glomeruli had an incidence of 50 +/- 10% in ADR rats versus
      2 +/- 1% in controls (P < 0.001). Immunohistochemistry revealed apo A-I and apo A
      IV in the visceral epithelium. Apo E immunoreactivity and lipid deposits were
      observed in focal glomerular sclerotic lesions of ADR rats. Neither
      apolipoproteins nor lipids were detected in glomeruli of controls. Proximal
      tubular localization of apolipoproteins was extensive for apo A-I, apo A-IV and
      apo E, but no differences were observed in tubular deposition of apolipoproteins
      between ADR and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255517
TI  - ANCA in haemodialysis patients.
AB  - The prevalence of positive ANCA as well as the prevalence of PR-3 and MPO
      antibodies were examined in a cross-sectional sample of 1277 haemodialysis
      patients from 16 German haemodialysis centres. We found 32 patients positive for
      c-ANCA (median titre 1:40; range 1:20-1:320) and 65 for p-ANCA (1:80; 1:20
      1:1280). Twenty-two percent of the c-ANCA-positive and 31% of the p-ANCA-positive
      patients had PR-3 and MPO antibodies by ELISA respectively. Clinical evidence of
      vasculitis was found in 11 of 32 c-ANCA-positive and 19 of 65 p-ANCA-positive
      patients. Of the 11 c-ANCA-positive, four had a known diagnosis of Wegener's
      granulomatosis (WG); WG was recognized after the test in a further five patients
      and two had renal limited RPGN. Of the 19 p-ANCA-positive patients, three had a
      clinical diagnosis of microscopic polyarteritis (MP), MP was newly diagnosed in a
      further 12, WG in one and renal limited RPGN in three. The patients had not
      received cyclophosphamide (the diagnosis had been non-specified 'systemic
      disease'). Thus false-positive ANCA, as defined by absence of vasculitis, was
      found in 5% of dialysis patients versus 0% in patients with preterminal renal
      failure (n = 152) or blood donors (n = 150). Patients with vasculitis tended to
      have higher c-ANCA and p-ANCA titres respectively, but there was a considerable
      overlap. Titres were not higher in patients symptomatic at the time of
      examination (6 of 11 c-ANCA and 10 of 19 p-ANCA), but PR-3 and MPO ELISA were
      positive in all but two.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255518
TI  - Monitoring of iron requirements in renal patients on erythropoietin.
AB  - We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis, 11 advanced
      renal failure) over the first 12 weeks of erythropoietin therapy. In 14 iron
      overloaded patients (ferritin > 500 micrograms/l the haemoglobin (+/- SEM)
      increased from 6.74 +/- 0.27 to 9.85 +/- 0.36 g/dl (P < 0.0001) entirely by
      mobilizing iron reserves (reduced from 1,220 +/- 73 to 739 +/- 111 mg, P <
      0.0001). In the 24 non-overloaded patients (ferritin < 500 micrograms/l) the
      haemoglobin rose similarly from 7.04 +/- 0.18 to 10.70 +/- 0.36 g/dl (P <
      0.0001), partly from iron reserves (depleted from 200 +/- 74 to -44 +/- 77 mg, P
      = 0.016) and partly from oral iron supplements (305 +/- 110 mg). In the
      overloaded patients the ferritin declined from 1057 micrograms/l (geometric mean,
      range 504-3699) to 317 micrograms/l (42-1505, P < 0.0001). In the non-overloaded
      patients it declined from 82 micrograms/l (8-461) to 45 micrograms/l (5-379, P =
      0.016). The transferrin saturation (TS) in the overloaded patients appeared to
      decline from 38.3 +/- 7.2% to 24.0 +/- 3.7% but this was not statistically
      significant. In the non-overloaded the TS was unchanged (23.3 +/- 2.4 before and
      28.1 +/- 3.6% after treatment). Considering all 38 patients together, the
      haemoglobin correlated negatively with the ferritin (r = 0.3731, P < 0.001) but
      not with the TS. The TS correlated with the serum ferritin initially (r = 0.75, P
      < 0.001) but not after the first 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255519
TI  - Acid-base responses to high-volume haemofiltration in the critically ill.
AB  - We have studied the acid-base and cardiorespiratory effects of intermittent
      pumped high-volume venovenous haemofiltration (HVHF) using replacement fluid
      containing lactate as the source of bicarbonate in critically ill patients. We
      demonstrated significant hyperlactataemia throughout the procedure, but there was
      no deterioration in acid-base status, haemodynamics, or oxygen delivery. These
      observations suggest that the worsening of acidosis and the hypotension that have
      been described with this technique can be avoided by appropriate monitoring and
      resuscitation prior to haemofiltration, and may be due to unrecognized
      inadequacies in the oxygen transport system.

PMID- 8255520
TI  - Effect of prophylactic ganciclovir on cytomegalovirus infection in renal
      transplant recipients.
AB  - Cytomegalovirus (CMV) infection is the most frequent infectious complication
      observed in renal-transplant recipients and induces a significant morbidity in
      these patients due to CMV disease itself and to associated renal dysfunction or
      opportunistic superinfection. In order to evaluate the effect of gangiclovir
      prophylaxis we conducted an open-label prospective randomized study of
      ganciclovir administration in CMV seronegative recipients of a renal allograft
      from CMV seropositive donors. Ganciclovir (5 mg/kg b.i.d./day for 14 days) was
      started on day 14 after transplantation. Thirty-two patients were included in
      this study (15 in the control group, 17 in the ganciclovir group). There was no
      significant difference between the two groups for age, immunosuppressive regimen,
      number of rejection, steroid pulses, and OKT3 treatments. Renal and patient
      outcomes were similar in both groups. The rate of CMV infection and CMV disease
      were similar in both groups (80% and 73.3% in the control group versus 70.6% and
      47.1% in the ganciclovir group; P = NS). Less severe CMV disease was observed in
      the ganciclovir group compared to controls. The delay between transplantation and
      CMV infection was significantly longer in the ganciclovir group compared to
      control group (68.1 +/- 5.1 versus 44.0 +/- 5.2 days, P < 0.005). Twelve group
      patients (80%) versus nine (53%) of the ganciclovir group required curative
      treatment with ganciclovir after the diagnosis of CMV infection (NS). All the
      patients recovered from CMV disease and no significant side effect was observed
      during ganciclovir administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255521
TI  - Serum lipoprotein (a) in renal transplant recipients receiving cyclosporin
      monotherapy.
AB  - Coronary heart disease is more common in patients with chronic renal failure and
      is a major cause of death after renal transplantation. Elevated serum lipoprotein
      (a) (Lp(a)) is a known risk factor for coronary heart disease in the general
      population. We measured the serum concentration of Lp(a) in 58 renal transplant
      recipients (40 male, 18 female) on cyclosporin monotherapy, and in 58 age- and
      sex-matched controls. Serum Lp(a) was significantly elevated in the transplant
      patients with a median of 27.5 (range < 0.8-140.3) mg/dl compared to 7.6 (range <
      0.8-87.4) mg/dl in controls (P < 0.001). Total serum cholesterol, low-density
      lipoprotein cholesterol, and total triglyceride concentrations were also
      significantly raised (P < 0.001) in the transplant recipients. The increased
      serum Lp(a) may contribute to the increased cardiovascular morbidity associated
      with renal transplantation.

PMID- 8255522
TI  - Bone tuberculosis: an unusual case of mycobacterial infection in a renal
      allograft recipient.

PMID- 8255523
TI  - Antineutrophil cytoplasmic autoantibody associated vasculitis and renal failure
      in Behcet disease.

PMID- 8255524
TI  - Human urogenital myiasis due to Eristalis larva: an unusual cause of ureteric
      obstruction.

PMID- 8255525
TI  - Radiological retrieval of transplant ureteric stents.

PMID- 8255526
TI  - Acanthocyturia detects glomerular bleeding.

PMID- 8255527
TI  - Beneficial effects of calcium antagonists on cyclosporin nephrotoxicity after
      clinical renal transplantation.

PMID- 8255528
TI  - Demographic data about The Netherlands.

PMID- 8255529
TI  - Mycobacterium bovis infection complicating renal transplantation.

PMID- 8255530
TI  - Peroxidase procedure in renal sections already prepared for immunofluorescence
      microscopy.

PMID- 8255531
TI  - Soft-tissue calcification after subtotal parathyroidectomy.

PMID- 8255532
TI  - Is the development of 'de novo' allograft membranes nephropathy linked to
      ureteric obstruction?

PMID- 8255533
TI  - Capsaicin applied to rat lumbar intervertebral disc causes extravasation in the
      groin skin: a possible mechanism of referred pain of the intervertebral disc.
AB  - Administration of 10 micrograms of capsaicin into the anterior portion of a
      lumbar intervertebral disc of rats pretreated with Evans blue (i.v.) caused dye
      extravasation in the groin skin. This phenomenon occurred even when the spinal
      nerve of the same segment, bilateral sympathetic trunks, and/or the anterior L2
      spinal root had been cut; it did not occur in rats with a cut genitofemoral
      nerve. Infiltration of capsaicin solution directly into the genitofemoral nerve
      did not cause dye extravasation. These results suggested the presence of
      dichotomizing sensory C-fibers which innervate both the intervertebral discs and
      the groin skin in the L2 spinal nerve. If such dichotomizing fibers exist in man,
      they may contribute to the groin pain sometimes associated with intervertebral
      disc lesions.

PMID- 8255534
TI  - 3,5,3'-L-triiodothyronine regulation of beta-adrenergic receptor density and
      adenylyl cyclase activity in synaptosomal membranes of aged rats.
AB  - To determine the effect of aging on T3 up-regulation of beta-adrenergic receptor
      activity of purified synaptosomal membranes (SPM), beta-adrenergic receptor
      density (Bmax) and adenylyl cyclase (AC) activity were measured in young (6
      months old) and aged (26 months old) male F-344 rats at baseline and after
      treatment with triiodothyronine (T3), 15 micrograms/100 g, intraperitoneally for
      10 days. The Bmax (fmol/mg protein) as measured by 125I-iodocyanopindolol binding
      was reduced in aged rats (70.8 +/- 4.1) compared to young rats (93.5 +/- 11.2).
      T3 treatment resulted in a significant increase in Bmax of young rats but not in
      aged rats (P < 0.05). The AC activity (pmol cAMP/mg) in response to prostaglandin
      E1 (PGE1) was reduced in aged rats compared to young rats (67.8 +/- 2.9 vs 108.3
      +/- 18.6; P < 0.01). The sodium fluoride (NaF) stimulated AC activity was not
      altered with age. A net isoproterenol stimulated AC activity could not be
      demonstrated in any age group. T3 treatment did not alter AC activity of SPM. It
      is concluded that aging is associated with reduced responsiveness to T3
      stimulated up-regulation of beta-adrenergic receptor number in synaptosomal
      membranes.

PMID- 8255535
TI  - An increase in the growth of hair associated with hyperinnervation of the
      underlying vessels in rabbit skin.
AB  - The localization of sympathetic nerves was studied histochemically in specimens
      of abdominal free flaps or revascularized graft and anastomosed epigastric
      arteries (i.e. the cut epigastric artery was resutured) from the operated and
      contralateral sides of rabbits, compared to controls. In the abdominal skin from
      control animals, noradrenaline-containing nerves were seen around blood vessels,
      hair follicles, sweat glands and dermis. In the free flaps, no noradrenaline
      containing nerves were present after day 7. However, on the contralateral side,
      there was an increase in the density of these nerves by day 30, compared with
      controls. In the epigastric artery, noradrenaline-containing nerves were confined
      to the adventitial-medial border in control animals and were absent from the
      anastomosed epigastric arteries, but on the contralateral side they penetrated a
      third of the medial wall by day 15. Concomitantly, there was excessive growth of
      hair on the contralateral side. Understanding of the mechanism involved may be of
      importance in solving the problems associated with hair loss.

PMID- 8255536
TI  - Characteristics of [125I]omega-conotoxin MVIIA binding to rat neocortical
      membranes.
AB  - [125I]omega-Conotoxin MVIIA (omega-CTM) binding to N-type voltage-sensitive
      calcium channels (VSCCs) was characterized using rat neocortical membranes.
      [125I]omega-CTM bound rapidly and with high affinity; these parameters were
      similar to binding using omega-conotoxin GVIA ([125I]omega-CTG). Unlike
      [125I]omega-CTG, however, [125I]omega-CTM readily dissociated from its binding
      site. Monovalent and divalent cations, polyamines, and aminoglycosides inhibited
      [125I]omega-CTM binding. Since [125I]omega-CTM appears to bind to the same site
      as [125I]omega-CTG in mammalian neurons, the reversibility of [125I]omega-CTM
      binding makes this ligand preferable for equilibrium binding analyses.

PMID- 8255537
TI  - Prostaglandin E2-induced sensitization of the heat response of canine visceral
      polymodal receptors in vitro.
AB  - The sensitizing effect of prostaglandin (PG) E2 on the heat response of
      testicular polymodal receptors was studied in vitro by recording single polymodal
      receptor activities from the testis-spermatic nerve preparations excised from
      deeply anesthetized dogs. PG E2 at 10(-7) M had no significant influence on the
      heat response. PG E2 at 10(-6) and 10(-5) M did not induce substantial increases
      in discharge rates, yet it significantly augmented the heat response. The
      concentration necessary for augmenting the heat response is thus 100 times
      greater than that (10(-8) M) previously reported for bradykinin [Naunyn
      Schmiedebergs Arch. Pharmacol., 344 (1991) 368-376].

PMID- 8255538
TI  - Alterations of Ca2+ currents and their sensitivities to Ca2+ antagonists during
      application and after deprivation of nerve growth factor.
AB  - The alterations in morphology and Ca2+ currents (ICa) were assessed in PC12
      cells, which were (1) control (untreated), (2) treated with nerve growth factor
      (NGF), and (3) deprived of NGF. NGF treatment induced neuronal differentiation
      morphologically and increased the current density of ICa, and especially that of
      the omega-conotoxin (omega-CgTX)-sensitive component. NGF-deprived cells
      manifested morphological deterioration and did not exhibit remarkable changes in
      the current density of the total ICa and dihydropyridine components, whereas the
      omega-CgTX-sensitive ICa component was decreased significantly compared with that
      in NGF-treated cells. The results suggest that the total function of Ca2+
      channels, including the dihydropyridine component, does not seem to be lost at
      the initial stage of neuronal deterioration, whereas omega-CgTX-sensitive Ca2+
      channels lost their function early.

PMID- 8255539
TI  - Autoradiographic analysis of serotonin receptors and transporter in kindled rat
      brain.
AB  - While serotonin (5-HT) has been shown to be anticonvulsant in several types of
      experimentally induced seizures, 5-HT receptor binding has not been investigated
      in the kindling model of epilepsy. The present study examined the effects of
      amygdala kindling on two 5-HT receptor subtypes and on the 5-HT transporter in
      rat brain. Kindling induced a persistent bilateral increase in 5-HT1A binding in
      the dentate gyrus, while 5-HT1B receptors increased only in a delayed fashion.
      Binding to the 5-HT transporter was transiently decreased in dentate gyrus. In
      cerebral cortex, binding of the three ligands was unchanged. Alterations in 5-HT
      receptors and the 5-HT transporter may endogenously modulate kindled seizures.
      Additionally, autoradiography of adenosine A1 receptors revealed no change for
      these receptors in any brain region.

PMID- 8255540
TI  - Sensory reinnervation of muscle receptor in human.
AB  - This report describes sensory reinnervation of muscle receptors in humans. In
      this study, sensory function was investigated in fourteen patients with brachial
      plexus injury, whose musculocutaneous nerve was surgically sutured with
      intercostal nerves for reconstruction of elbow flexion. Tapping the intercostal
      nerve-reinnervated brachial biceps muscle (IC-biceps) induced somatosensory
      evoked potentials (IC-biceps SEP) in four patients. Tapping also induced reflex
      IC-biceps activity in all IC-biceps SEP (+) patients, but not in eight out of
      nine IC-biceps SEP (-) patients. Results show that muscle afferent fibers in the
      intercostal nerves reinnervated mechanoreceptors in IC-biceps, and induced both
      cortical sensory activity and muscle activity that indicated the classical
      stretch reflex.

PMID- 8255541
TI  - Retinopetal projections from diencephalic neurons in a primitive actinopterygian
      fish, the sterlet Acipenser ruthenus.
AB  - Horseradish peroxidase (HRP) injections into the sterlet (Acipenser ruthenus)
      retina retrogradely label neurons in the dorso-medial thalamus, bilaterally. On
      the contralateral side, 5-7 cells were labelled, whereas ipsilaterally, only 2-3
      cells were backfilled. Such diencephalic retinopetal cells have, so far, only
      been found in teleosts and in tetrapods. It has, therefore, been suggested that
      they evolved independently in these two vertebrate groups. Our findings on a
      primitive actinopterygian fish, suggest a more ancient origin of diencephalic
      projections to the retina.

PMID- 8255542
TI  - Characterization of proteases with the specificity to cleave at the secretase
      site of beta-APP.
AB  - The beta-amyloid precursor protein (APP) can be proteolytically processed in at
      least two different ways either in a secretory pathway or in a lysosomal pathway.
      The proposed sites for the 'secretase' cleavage are the Gln15-Lys16 and Lys16
      Leu17 peptide bonds within the beta A4 domain. Using chromogenic peptide
      substrates derived from these APP sites, proteolytic enzymes were investigated in
      the brain of AD patients and control individuals. Mean differences in enzyme
      activity were observed between the two groups, although no statistical
      significance was reached. Further analysis in rat brain allowed identification of
      the lysosomal cathepsin B and the cytosolic proteasome as secretase-like enzymes.
      They are probably not involved in APP secretion but possibly in removal of
      amyloidogenic fragments.

PMID- 8255543
TI  - Response of rat cerebral glycolytic enzymes to hyperammonemic states.
AB  - Activity levels of enzymes of glycolytic pathway viz., hexokinase (EC.2.7.1.1),
      phosphofructokinase (EC.2.7.1.11), aldolase (EC.4.1.2.13), glyceraldehyde-3
      phosphate dehydrogenase (EC.1.2.1.12), enolase (EC.4.2.1.11), pyruvate kinase
      (EC.2.7.1.40) and lactate dehydrogenase (EC.1.1.1.27) were estimated in cerebral
      cortex, cerebellum and brainstem of the rats treated with subacute and acute
      doses of ammonium acetate and compared with those of control animals. In general,
      the activities of all the enzymes except for hexokinase and lactate
      dehydrogenase, were elevated in all the three regions of the brain. The results
      suggests an enhanced rate of glycolysis in brain in hyperammonemic states and
      strengthens the role of ammonium ion in stimulating certain enzymes of the
      glycolytic pathway.

PMID- 8255544
TI  - Autoradiographical evaluation of [3H]glycine uptake in rat forebrain: cellular
      localization in the hippocampus.
AB  - The cellular elements responsible for the uptake of [3H]glycine into rat
      hippocampal slices were investigated. The diffuse laminar distribution of
      labelling observed under control conditions was greatly reduced seven days after
      intrahippocampal injection of a neurotoxic dose of quinolinic acid, suggesting a
      neuronal localization. Glycine was also taken up into glial cells, since dense
      clusters of silver grains were present on small sized cells throughout the
      hippocampus which were apparently increased in number after the lesion. The
      pattern of [3H]glycine uptake into rat cerebral cortex and cerebellar slices was
      also consistent with both neuronal and glial localization. These glycine
      transport sites may be strategically located to control excitatory
      neurotransmission mediated by the N-methyl-D-aspartate sub-type of glutamate
      receptors.

PMID- 8255545
TI  - Anti-nociceptive effects of the GM1 ganglioside derivative AGF 44 on the formalin
      test in normal and streptozotocin-diabetic rats.
AB  - The effect of AGF 44, an ester derivative of ganglioside GM1, on formalin-induced
      nociceptive behavior was examined in normal and streptozotocin-diabetic rats. AGF
      44 (30 mg/kg/day i.p. for 7 days) produced a significant reduction of the second
      phase (20-40 min) and a lesser degree of suppression of the first phase (1-2 min)
      of the formalin test in both control and diabetic rats. Diabetic rats showed an
      increased response during the quiescent period (5-16 min) which was ameliorated
      by treatment with AGF 44 (30 mg/kg i.p.) for the last 7 days of a 5 week period
      of diabetes. These results indicate that AGF 44 can diminish responses to a
      prolonged nociceptive stimulus in both normal and diabetic rats and reduces the
      exaggerated nociceptive behavior of diabetic rats.

PMID- 8255546
TI  - Sexual differences in the synaptic connectivity in the rat dentate gyrus.
AB  - The volume density of synapses in the hilus of the dentate gyrus was
      quantitatively assessed in adult rats. A gender difference was found, with males
      showing a significantly higher number of mossy fiber synapses. Other types of
      nerve endings on dendritic shafts and dendritic spines were not different between
      the two sexes. Since it has been previously shown that the volume density of
      mossy fiber synapses in the CA3 area of the hippocampus is higher in females than
      in males, the present findings suggest that the sexually dimorphic synaptic
      patterns may be determined not only by the presynaptic elements, but also by the
      postsynaptic target area.

PMID- 8255547
TI  - Effects of intrathecal FK888, a novel dipeptide NK1 receptor antagonist, on the
      formalin test in the rat.
AB  - This study investigates the effects of intrathecally administered FK888, a novel
      dipeptide NK1 receptor antagonist, on the formalin test in the rat. Subcutaneous
      formalin induces biphasic episodes of flinching behavior at 0-5 min (Phase 1) and
      10-60 min (Phase 2) after treatment. FK888 administered intrathecally 10 min
      before the formalin injection depresses the Phase 2 flinching behavior in a dose
      dependent manner, but not the Phase 1 flinching behavior. FK888 has no effect on
      the Phase 2 flinching behavior when administered intrathecally 60 min before or 9
      min after the formalin injection. Intrathecally administered FK888 has no effect
      on the motor function. These results suggest that FK888 is good drug to study the
      role of the NK1 receptor in the spinal cord of the rat.

PMID- 8255548
TI  - Neuropeptide Y modulation of A1 noradrenergic neuron input to supraoptic
      vasopressin cells.
AB  - A1 noradrenaline (NA) neurons provide a direct excitatory input to supraoptic
      nucleus (SON) vasopressin (VP) cells. Many A1 cells contain neuropeptide Y (NPY)
      and past studies have established that NPY exerts excitatory postsynaptic effects
      on VP cell activity. We have now investigated whether NPY might also modulate A1
      input to VP cells via presynaptic mechanisms. Experiments done in pentobarbitone
      anesthetized rats demonstrated that SON application of NPY (10 microM) excited VP
      cells but also depressed their response to activation of the A1 input. These two
      effects were not correlated, suggesting independent mechanisms. The putative Y1
      agonist [Leu31,Pro34]NPY (10 microM) also excited VP cells but did not alter
      their response to activation of the A1 input. In contrast, the putative Y2
      receptor agonist Ac-[Leu28,Leu31]NPY24-36 mimicked the synaptic depression
      produced by NPY but did not significantly alter spontaneous activity. These data
      are consistent with the proposal that NPY acts on Y1-like receptors to excite VP
      cells but can also act on a presynaptic Y2-like receptor to depress A1-VP cell
      synaptic transmission.

PMID- 8255550
TI  - Changes of regional cerebral blood flow during listening to an unfamiliar spoken
      language.
AB  - The regional cerebral blood flow (rCBF) was measured with positron emission
      tomography in eight normal volunteers with the purpose of measuring rCBF changes
      related to the comprehension of an unfamiliar spoken languages. When attempting
      to comprehend the meaning of words, the left hemisphere showed dominant increases
      in rCBF, however, when subjects attempted to evaluate the emotional tone of the
      same spoken passage, relatively large increases in rCBF more found in the right
      hemisphere. The results indicate that there may be several different auditory
      representations of language which involve both left and right hemispheres, both
      of which may contribute to the overall comprehension of spoken language.

PMID- 8255549
TI  - Diode laser irradiation selectively diminishes slow component of axonal volleys
      to dorsal roots from the saphenous nerve in the rat.
AB  - Ga-Al-As laser irradiation (830 nm wavelength) inhibits the action potentials in
      the dorsal roots elicited from the saphenous nerve of the rat. Following laser
      irradiation to the saphenous nerve, the amplitude of slower conduction parts of
      action potentials (conduction velocity < 12 m/s) were suppressed. This
      suppression was irradiation time dependent. After 3 min irradiation, slowest
      conduction velocity group (< 1.3 m/s) were totally diminished and 1.3-12 m/s
      group were reduced to 12-67%. In contrast, faster component (> 12 m/s) was
      unaffected by laser irradiation. These findings suggest that laser irradiation
      may selectively target fibers conducting at slow velocities which include
      afferent axons from nociceptors.

PMID- 8255551
TI  - Extracellular release of acetylcholine, noradrenaline and serotonin increases in
      the cerebral cortex during walking in conscious rats.
AB  - The effect of walking on the extracellular release of acetylcholine (ACh),
      noradrenaline (NA) and serotonin (5-HT) in the parietal lobe of the cerebral
      cortex was examined in conscious rats using the microdialysis technique. Walking
      at the speed of 2.3 m/min for 5 min produced significant increases in ACh, NA and
      5-HT release in the cerebral cortical extracellular space. The increase in ACh
      release was the most prominent among the transmitters examined. It is suggested
      that the increased release of ACh in the cerebral cortex may contribute at least
      partly to the increases in the cerebral cortical blood flow during walking.

PMID- 8255552
TI  - Brain methionine- and leucine-enkephalin receptors in patients with dementia.
AB  - Brain [3H]Met- and [3H]Leu-enkephalin binding was studied in patients with
      Alzheimer's disease (AD) and vascular dementia (VD), and in age-matched controls.
      Brain areas investigated were the internal and external globus pallidus,
      amygdala, hippocampus and temporal cortex. In AD, the binding of both enkephalins
      decreased in all brain areas examined, except in the external globus pallidus for
      both enkephalins and in the internal globus pallidus for leucine-enkephalin.
      Scatchard analysis of amygdaloid samples showed a decrease in the number of
      receptors (Bmax) without any change in their affinity (Kd). In patients with VD,
      no significant changes in enkephalin binding were seen. Thus, in AD, enkephalin
      binding (mainly reflecting delta opioid receptor subtype) is decreased,
      especially in limbic areas.

PMID- 8255553
TI  - Halothane acts on many potassium channels, including a minimal potassium channel.
AB  - There has been considerable controversy over whether general anesthetics act
      directly on membrane proteins, and if so, whether there are uniquely sensitive
      protein targets upon which they act. Here, we examine the actions of halothane on
      a diverse collection of voltage-gated potassium channels expressed in Xenopus
      oocytes, and find that they are all sensitive at clinically relevant
      concentrations. To investigate further the molecular basis of this commonality,
      human and rat minimal potassium (minK) channels, which have exceedingly short
      amino acid sequences, were examined. Current through these channels is reversibly
      reduced to 68% of control values by 0.5% (0.34 mM) halothane. A double deletion
      mutant of the 130-amino acid minK protein, in which 30 amino acids of the N
      terminus, thought to be extracellular, and 37 amino acids of the putative
      intracellular C-terminus are deleted (resulting in a protein in which more than
      half of both the extracellular and intracellular domains have been removed)
      responds to low halothane concentrations similarly to the parent channel. While
      alternative explanations are possible, this result is consistent with a model
      whereby halothane interacts with the channel protein from within the lipid
      bilayer.

PMID- 8255554
TI  - Alterations of locus coeruleus noradrenergic activity in relation to pituitary
      secretion after hemorrhage in cats.
AB  - Noradrenergic (NA) activity in the cat ventral locus coeruleus (vLC), measured
      either by voltammetry or by push-pull perfusion, increased in response to
      hemorrhage. This stimulus also elicited plasma adrenocorticotropin (ACTH) and
      vasopressin responses. Increased vLC NA activity following the initial hemorrhage
      (InHem) persisted even after plasma hormone levels returned toward prestimulus
      values. Upon stimulus repetition, the peak increase in vLC NA activity was
      similar to that observed during InHem while the hormone responses were of greater
      magnitude (i.e. potentiated). Hence, it is suggested that the LC may exert a
      modulatory role in the hemodynamic control of hypothalamic-pituitary axis
      function.

PMID- 8255555
TI  - Microglial reaction in Pick's disease.
AB  - Number and morphology of microglial cells (MC) were compared in 6 cases each of
      Pick's disease (PD), Alzheimer's disease (AD) and controls using
      immunohistochemistry with the monoclonal antibody Ki-M1P. The severely involved
      neocortex of both PD and AD, and in particular the white matter subjacent to
      spongy PD lesions showed a marked increase of MC density, whereas non-affected PD
      areas and AD white matter showed no MC changes. The PD hippocampus, particularly
      the dentate gyrus, showed reduction of MC density and processes. We conclude that
      (1) MC reaction represents a major element of PD histopathology, and (2) density,
      morphology and distribution of MC are different in AD and PD.

PMID- 8255556
TI  - Amphetamine enhances human-memory consolidation.
AB  - Although it is generally accepted that CNS stimulants have enhancing effects on
      long-term storage processes in laboratory animals, little is known about their
      influence on human learning. We report a series of experiments with free recall
      of lists of unrelated words, demonstrating a significant enhancement on long-term
      retention after amphetamine administration. A gradual increase of recall was
      observed up to 1 h after learning, remaining stable for at least 3 days, after
      oral administration before learning as well as intramuscular injection after
      learning. The results show that research on humans with drug-induced memory
      enhancement techniques is necessary to supplement the animal studies for the
      understanding of the mechanisms involved in information consolidation.

PMID- 8255557
TI  - The excitatory response of the adrenal sympathetic nerve to severe hypoxia
      decreases in aged rats.
AB  - The age-related changes in the sensitivity of the adrenal sympathetic nerve to
      hypoxia were investigated in anesthetized young adult (3-4 months old) and aged
      rats (25-26 months old). Hypoxia with end-tidal O2 concentration (FETO2) at 6-2%
      caused excitation of adrenal nerve activity in the young adult and the aged rats.
      There was a significant decrease in the responses at 3 and 2% FETO2 in the aged
      rats compared to the young adult rats at either peripheral chemoreceptors-intact
      or -denervated condition. Reduced responsiveness of the central chemoreceptors to
      severe hypoxia is suggested as a possible factor in the age-related decreases.

PMID- 8255558
TI  - Cost of coronary heart disease in New Zealand.
AB  - AIM: To conservatively estimate the costs of coronary heart disease from the
      perspective of New Zealand society. METHODS: A cross sectional or prevalence
      analysis (cases and associated costs in one year) was undertaken of the total
      annual cost of coronary heart disease. Estimates were made on an incremental
      basis of direct, indirect and intangible costs. Costs relate to 1989 volumes
      measured in March quarter 1992 dollars (net of goods and services tax). RESULTS:
      Cost estimates were in all instances conservative values. Direct medical costs
      amounted to $179 million and indirect costs were between $14 million and $24
      million. Loss of life using the human capital approach ranged from $114 million
      to $264 million, but using the willingness to pay criteria, loss of life was
      $14,568 million. CONCLUSION: Because of the magnitude of the costs of coronary
      heart disease even small reductions in the incidence of coronary heart disease
      will produce substantial savings to society.

PMID- 8255560
TI  - Women's health research in New Zealand.

PMID- 8255559
TI  - Giardiasis in Canterbury: the first nine months reported cases.
AB  - AIM: To obtain epidemiological information about giardiasis in Canterbury.
      METHOD: From October 1990 general practitioners were requested to report
      laboratory confirmed cases. The first 100 cases were sent a questionnaire and
      also asked to provide the details of two persons to be controls. RESULTS: In the
      first nine months 109 cases were reported. Eighty four cases completed
      questionnaires and 51 were matched with controls. The overall reported attack
      rate was 4.0 per 10,000 population per year. The rate was highest for preschool
      children and young adults and in rural areas. There was a significant risk
      associated with having contact with sewage or travelling overseas and a marginal
      risk for drinking water outside Christchurch. CONCLUSION: The results indicated
      that giardiasis was relatively common in Canterbury and confirmed that the major
      mechanisms of infection were probably the same as those previously identified
      overseas, namely person to person spread via faecal-oral transmission and the
      drinking of inadequately filtered water.

PMID- 8255561
TI  - A community wide promotion of asthma self management: process evaluation.
AB  - AIMS: During the months February through July 1991, a community wide promotion of
      asthma self-management was undertaken as a pilot study for the national launch of
      an asthma action plan developed by the Asthma Foundation of New Zealand in
      conjunction with the Royal New Zealand College of General Practitioners. METHODS:
      A multidisciplinary team of hospital and community-based health workers was
      established, with the aim of educating and resourcing general practitioners,
      practice nurses and retail pharmacists to enable them to effectively promote and
      distribute the asthma action plan. 332 general practitioners and 148 retail
      pharmacists were surveyed through postal and telephone questionnaires at the
      completion of the promotion, to assess its impact on health professionals and to
      obtain feedback for the national promotion of the asthma action plan. RESULTS:
      108 (73%) of pharmacists who responded and were involved with the promotion found
      their participation to be worthwhile, although some had difficulty allocating
      sufficient time to give detailed advice to patients. Of the 240 general
      practitioners who responded, 77% indicated that they had used the asthma action
      plan with their patients. They were positive about the use of the workshop format
      that had provided education and resources for the plan, and of those that had
      used the plan, 94% indicated that they would continue to promote the plan, or one
      similar. CONCLUSIONS: The promotion of the asthma action plan in Canterbury had a
      major impact on health professionals. The community-wide promotion might have had
      a greater impact on people with asthma had television advertising been used. The
      pilot project provided useful feedback for the Asthma Foundation in their
      preparation for the national launch.

PMID- 8255563
TI  - A study of the content and clarity of general practitioner referral letters to an
      emergency department.

PMID- 8255562
TI  - Increasing the uptake of cervical smears: strategies implemented among general
      practitioners in Auckland.
AB  - AIM: To evaluate three strategies designed to increase the uptake of cervical
      smears among specified groups of women through a collaborative partnership
      between the Auckland Area Health Board and selected Auckland general
      practitioners. METHOD: Using action-based research general practitioners and
      practice nurses were engaged to initiate ways of inviting women in their
      practices to have cervical smears. Both formative and process evaluations were
      made. Concurrently, outcomes were measured in terms of call/recall systems,
      uptake rates and cost barriers. RESULTS: Where financial incentives were given to
      establish call/recall systems for older women, overall uptake rates increased by
      21%, and by 154% for women over 45 years. Over one third of a targeted group of
      women aged between 60 and 70 years responded to an invitation to have a free
      smear. Of these 109 women, fourteen, with a median age of 67 years, had their
      first smear. Almost two thirds indicated that cost had never been a barrier.
      CONCLUSIONS: The determining factor for women having a cervical smear in all
      three strategies was a personal invitation from their general practitioner or
      practice nurse. Invitations were dependent upon having accurate call/recall
      systems. This evaluation of the collaborative process between Auckland Area
      Health Board and local general practitioners demonstrated how manager and
      provider partnerships can benefit the consumer.

PMID- 8255564
TI  - First annual report of the New Zealand Preferred Medicines Centre 1993.

PMID- 8255565
TI  - Betamethasone rules OK!

PMID- 8255566
TI  - Food for New Zealanders.

PMID- 8255567
TI  - In vitro fertilisation and gamete intrafallopian transfer.

PMID- 8255569
TI  - Improving immunisation uptake.

PMID- 8255568
TI  - Solvent-induced hyperactivity.

PMID- 8255570
TI  - [Causes, diagnosis and therapy of habitual abortions].
AB  - Recent knowledge concerning the etiology of habitual abortions is reviewed by the
      author. The anatomic, genetic, endocrine and immunologic causes furthermore the
      assumed role of maternal diseases and infections are summarised. Besides
      diagnostic procedures and therapeutic possibilities are discussed.

PMID- 8255571
TI  - [Value of the ejection fraction in patients with right ventricular necrosis
      during the rehabilitation period].
AB  - The right ventricular ejection fraction was determined in 58 patients with
      simultaneous right and left ventricular myocardial infarction and in 77 patients
      with only left ventricular myocardial infarction. The results were analysed in
      four groups of patients (patients with anterior, anterior and right ventricular,
      posterior, posterior and right ventricular myocardial infarction). Furthermore,
      the relation between left and right ventricular ejection fraction, stress
      capacity and heart volume was investigated. There was no influence of the age and
      gender of patients on the observed values of right and left ventricular ejection
      fraction. In younger patients, after myocardial infarction, the heart volume was
      found to be less and the stress capacity to be higher then in elderly patients.
      The right ventricular ejection fraction was normal in patients with "poor" left
      ventricular infarction, and it was decreased in patients with right ventricular
      myocardial infarction. The right ventricular ejection fraction did not influence
      the stress capacity and the heart volume of the patients. The left ventricular
      ejection fraction found to be less in anterior, compared to posterior myocardial
      infarction. This difference was independent on the presence of right ventricular
      infarction. The authors consider the decreased right ventricular ejection
      fraction as a valuable indicator of the abnormal contractility of the right
      ventricle even at the time of the rehabilitation after myocardial infarction.

PMID- 8255572
TI  - [The place of pentachlorophenol in general medicinal practice].
AB  - Pentachlorophenol is a substance whose widespread use has led to substantial
      environmental contamination. Causing local irritations the pentachlorophenol can
      be absorbed into the body by all the routes of occupational exposure. The acute
      pentachlorophenol intoxication is dangerous for the life: its quick diagnose and
      adequate therapy is very important. Chronic high pentachlorophenol exposure may
      increase the incidence of several diseases, eg. immunodeficiency, blood
      disorders, hepatic lesions and malignancies. The prevalence of alcoholism in
      working places applying pentachlorophenol is between 6 and 10 per cent, so the
      general practitioner of these workers should take precautions to distinguish
      between of drunkenness and acute pentachlorophenol intoxication.

PMID- 8255573
TI  - [Rasmussen syndrome].
AB  - Authors report about a boy with Rasmussen syndrome. This is a chronic localised
      encephalitis with focal epileptic seizures causing progressive neurologic
      deficits and mental impairment. The etiology and the clinical features of the
      syndrome are discussed, and the diagnostic role of the new imaging modalities is
      emphasized. This is the first report about this entity in Hungary.

PMID- 8255574
TI  - [The legacy of Albert Szentgyrgyi].

PMID- 8255575
TI  - [Scientific connections of Albert Szentgyorgyi in Serbia (on the centenary of the
      birth of the Nobel prize-winning Hungarian scientist)].

PMID- 8255576
TI  - [Sandor Koranyi in Hungarian public health].

PMID- 8255577
TI  - [Cholesterol level and diet].

PMID- 8255578
TI  - [Cholesterol levels and diet].

PMID- 8255579
TI  - [Duplex ultrasonography in the study of carotid and vertebral artery stenosis
      (comparison with intra-arterial digitalized subtraction angiography)].
AB  - A prospective comparison was completed between duplex sonography and
      intraarterial digitalized subtraction angiography of the carotid and vertebral
      arteries. The sensitivity, specificity and overall accuracy of the duplex
      ultrasound were evaluated. In 85 patients 169 sides were investigated. The
      vessels were divided into normal, 1-24%, 25-49%, 50-74%, 75-99% stenosis and
      occlusion categories. For stenoses of less than 50% in the proximal internal
      carotid artery, sensitivity and specificity were excellent (95 and 92%), for
      lesions causing more than 50% stenosis were 87 and 95%, respectively. The overall
      accuracy for 0-99% stenosis was 93% and for total occlusions increased to 99%.
      Sensitivity was lesser (49-54%), but the specificity (92-96%) and overall
      accuracy (85-86%) were good for the evaluation of common and proximal external
      carotid artery. Our results indicate that duplex scanning is a valuable technique
      for measurement of patency and direction of blood flow in the vertebral arteries.
      The conventional duplex ultrasound can be regarded as an accurate, relatively
      cheap, and nonevasive screening method for stenoses and occlusions of cervical
      carotid and vertebral arteries of patients with ischaemic cerebrovascular
      disease.

PMID- 8255580
TI  - [Postischemic inverted T waves: does gradual regression indicate improved
      prognosis?].
AB  - This study has followed up the natural history of postischemic inverted T waves
      and assessed the prognosis. 40 consecutive patients with unstable angina with
      postischemic precordial inverted T waves in the noninfarcted, previously ischemic
      area were followed during the persistence (negative T wave period) and after
      resolution of inverted T waves (positive T wave period). The outcome with
      frequencies of acute myocardial infarction, acute ischemic syndrome, angina
      pectoris, positive exercise test, silent myocardial ischemia, anterior wall
      motion abnormalities on echocardiogram, positive coronary arteriography were
      determined and compared in the negative versus positive T wave periods.
      Postischemic inverted T waves showed resolution within the postischemic 3-21 days
      (at a mean of 10.6 days) in 31 patients on medical treatment alone during the
      whole study period. Frequencies of parameters/patients determined in negative
      versus positive T wave periods are as follows: acute myocardial infarction: 5/40
      versus 0/31 (non significant), acute ischemic syndrome: 25/40 versus 2/31 (p <
      0.001), angina pectoris: 32/40 versus 11/31 (p < 0.001), positive treadmill
      exercise test: 14/16 versus 14/30 (p < 0.02), silent myocardial ischemia: 14/14
      versus 16/31 (p < 0.01), hypokinesis 26/34 versus 4/24 (p < 0.001), positive
      coronary arteriography: 4/4 versus 11/11 (non significant). In most patients on
      medical treatment, the postischemic inverted T waves tend to resolve within 3
      weeks. Attention has to be paid to the patients with postischemic inverted T
      waves during the negative T wave period: the high ischemic risk gradually
      decreases with resolution of negative T waves.

PMID- 8255581
TI  - [Antibiotic prophylaxis in cholecystectomy performed by micro- and modern mini
      laparotomy].
AB  - The authors review the results of the use of antibiotic prophylaxis (AP) during
      412 cases of micro (MLC) and modern mini-laparotomy cholecystectomy (MMLC). 2 gr
      of Mandokef (M) or 1.5 gr of Zinacef (Z) were the employed antibiotics,
      administered intravenously 30 minutes before the commencement of the operations.
      In the case of patients above the age of 50 AP was given on routine basis. Apart
      from cases of obstructive cholecystitis (OC), a single shot of Mandokef or
      Zinacef proved effective; there was no occurrence of suppuration. Out of 94 under
      fifty patients--where in accordance with the accepted standpoint applied to
      traditional cholecystectomy AP would not have been necessary--AP was administered
      in 43 cases: no suppuration occurred. 51 patients did not receive AP; here 2
      cases of suppuration occurred (4%). In 99 patients suffering from obstructive
      cholecystitis (OC), the single-shot AP was supplemented and continued with cover
      therapy where necessary. On the basis of the time elapsed between the
      presentation of the OC and the operation, the cases were classified in the
      following groups: 1.27 patients operated on within 10 days: no cases of
      suppuration or other complications II. 34 patients operated on between 10 days
      and 6 weeks: 2 cases (5.9%) III. 38 patients operated on after 6 weeks: 3 cases
      (7.9%) of suppuration or other complications were encountered. After MLC and MMLC
      the patients are emitted form hospital within 24-72 hours. However, 80% of the
      bacteria resoiling in the gallbladder can cause wound suppuration 4-10 days post
      operatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255582
TI  - [Submolecular theory of cancer. In memoriam Albert Szent-Gyorgyi].
AB  - The author surveys the way leading to the electronic theory of cancer and
      analyses the role of methylglyoxal and glyoxalases. Based on the comparison of
      experimental data with the theory it can be concluded that (i) data being at
      disposal are not convincing enough either to verify or to confute the theory;
      (ii) compounds having function to influence the glyoxalase system can, however,
      be considered as tumour-selective anticancer agents.

PMID- 8255583
TI  - [Carcinoma of the postcricoid area of the hypopharynx: treatment and results].
AB  - Squamous cell carcinoma arising in the postcricoid area of the hypopharynx is
      relatively late diagnose. Previous observation concerning patients treated in our
      Clinic and the data from literature confirmed very bad diagnosis in this cases.
      The results of the Clinical observation of 58 patients and pathomorphology
      findings in 35 preparates have been described. In that group we have found only
      16 cases (27.6%) with 3 years long surviving rate. Morphological findings,
      relating lymphatic system, partially explained so bed prognosis.

PMID- 8255584
TI  - [Neoplasms of neurilemmal sheath in the light of experience of the Department of
      Otolaryngology, Medical University in Krakow].
AB  - In the years 1986-91, five patients with neoplasms of neurolemmal sheath were
      treated in the Department of Otolaryngology, Medical University in Cracow. Two
      patients suffered from malignant neurinoma (malignant neurinoma of orbit or
      maxillary sinus) and the other three had neurinoma (neurinoma of the floor of
      mouth, nasal cavity and neck). There were four men and one woman. The age of
      patients ranged from 23 to 52 years. The tumors were surgically removed, patients
      with malignant neurinoma required additional irradiation. Currently, no tumor
      recurrence has been noticed.

PMID- 8255585
TI  - [The ultrasound examination of salivary gland].
AB  - The results obtained after the examination of 107 ultrasound cases of changed
      salivary glands were presented. The characteristic features for changes most
      often appearing in salivary glands were presented. In case of tumours and cysts
      the diagnosis was formed on the basis of the ultrasound character of the change
      (low homogenas, density in cysts, higher density, non homogenous character in
      tumours), the degree of separation from the surrounding tissue (clear capsule in
      cyst and benign tumours, lack of capsule, indistinctive image in change of
      malignant character, in case of infiltration of surrounding tissues). The
      diagnosis of inflammation was made depending on the character of the change of
      the parenchyma of salivary gland--the increase of the gland with the lowering of
      density characteristic for acute inflammation, the reduction of size, increased
      sonographic density, enlarged leading out (duct), the echo of concrement is
      characteristic together with the accompanying acoustic shade for bigger
      concrements.

PMID- 8255586
TI  - [Epidemiological risk factors of larynx cancer among natives and immigrants in
      the Upper Silesian region].
AB  - A case-control study has been used to analyse risk factors such as tobacco
      smoking, pollution exposure in the microenvironment of the place of work, ambient
      air pollution in the living place among natives and immigrants for larynx cancer
      in Upper Silesia Region. There were tested 399 cases (269 natives and 130
      immigrants) and 942 controls (557 and 385 respectively). Tobacco smoking and
      exposure to air pollution in the place of work is connected with increased
      incidence of larynx cancer risk among natives and immigrants. It was shown that
      there is no connection between larynx cancer and the degree of air pollution in
      the living place among natives.

PMID- 8255587
TI  - [Facial palsy in Equatorial Africa].
AB  - The author presents the analysis of 29 cases of facial palsy collected in Shaba,
      Zaire (former Katanga, Belgian Congo) between 1984-1988 in the region called
      Copperbelt. Because to date there has been no work done on these problems in this
      part of Africa, it would be interesting to present a short report. Patients with
      facial palsy came to the ENT Department mostly for other reasons, and very late.
      Only 5 patients came before 3 mos after the onset. The different etiologies were
      as follows: 2--post traumatic, 7--otogenic, 9--tumors, 4--iatrogenic, 6--Bells
      palsy, 1--other. The assessment, comparison and the treatment of such cases in an
      underdeveloped country is very difficult or almost impossible. The small number
      of cases is insufficient for any conclusions, but the author tried to get some
      data, which would be a starting point in the future researches.

PMID- 8255588
TI  - [Experimental studies of mechanism and efficiency of sclerosing agents: varicocid
      and paraffin].
AB  - Based on the analyse of publications the authors treated of history and
      contemporary applications of sclerotherapy. The role, methodics and results of
      sclerosing therapy among patients with oesophageal varices were also presented.
      The aim of the study was to examine the mechanism and efficiency of two
      sclerosing agents which are frequently used in Poland. Examinations were
      performed on 30 Wistar rats. Their caudal veins were injected with 0.1 ml of
      Varicocid or paraffin. In the control group the 0.9% solution of NaCl was
      applicated. Clinical and histologic appraisal were done at 3 weeks postinjection
      (first or second) of sclerosants. On the base of obtained results the necro
      inflammatory properties and considerable higher efficiency of Varicocid were
      confirmed.

PMID- 8255589
TI  - [Diagnostic value of the second phase nystagmus].
AB  - The aim of our work was the presence of the second phase nystagmus after
      rotatory, caloric and optokinetic irritation; estimation of this nystagmus
      magnitude and the clinical application of the second phase nystagmus. The
      investigation was performed in 30 healthy subjects and 65 cases of the peripheral
      and central vestibular pathology. Our results show that the second phase
      nystagmus appears more often after strong vestibular or visual irritation; the
      largeness of this reaction is bigger than the first reaction nystagmus. Only the
      asymmetry of the second phase nystagmus has the clinical apply. Labyrinthine
      disorders has the influence on the formation of the post-optokinetic reaction.

PMID- 8255590
TI  - [Diagnostic value of the peripheral and central vestibular recruitment and
      decruitment].
AB  - The subject of our investigation was the diagnostic value of the distinguish of
      peripheral and central type of the vestibular recruitment and decruitment. The
      examination was performed in the healthy subjects and in the two groups of the
      peripheral and central vestibular pathology cases. For the definition of the
      presence of peripheral or central type of the recruitment/decruitment phenomenon
      we used Ghosh and Kacker method for the labyrinth irritation. The results of this
      study show that for more detail topographic diagnosis of the vestibular disorders
      one must search the type of recruitment and decruitment.

PMID- 8255591
TI  - [Mechanism of hearing. I. Efferent system of innervation of the organ of Corti].
AB  - The authors present some morphological, physiological and pathophysiological
      aspects of efferent system of innervation (i.e. olivocochlear system) of the
      organ of Corti. The cochlea is innervated by two different systems: 1) the medial
      efferent system which originates in the medial nucleus of the trapezoid body and
      synapses on outer hair cells, 2) the lateral efferent system which originates in
      the superior olivary nucleus and synapses on the dendrites of the auditory nerve
      under inner hair cells. An electrical stimulation as well as an acoustic
      stimulation of efferent fibers results in: a) suppression of the auditory nerve
      response (N1 amplitude reduction), b) increase in amplitude of cochlear
      microphonics and c) reduction of the endolymphatic potential. Due to presence of
      the crossed olivocochlear bundle, an ipsilateral stimulation of efferent fibers
      results in both ipsi- and contralateral response. Efferent fibers response is a
      feedback response to afferent fibers stimulation. There are some evidence that
      efferent system of innervation protects the cochlea against the effects of
      intense sound exposure.

PMID- 8255592
TI  - [Follicular carcinoma of the ectopic lingual thyroid].
AB  - The ways of origin and the methods of diagnosing of the ectopic thyroid gland
      have been described. The authors have shown the case of follicular carcinoma of
      ectopic lingual thyroid gland in 35 years woman. The effective surgery
      (labiomandibuloglossotomy and total extirpation of the tumor) and following
      irradiation therapy with 131I haven't revealed recurrence of the disease during
      2.5 years observation. The permanent substitution therapy with thyroxine has
      secured the euthyreotic state for the patient.

PMID- 8255593
TI  - [Apudoma: a rare case of the laryngeal tumor].
AB  - The authors present the problem of endocrine function of some neoplasmatic tumors
      based on their own very rare case of the larynx apudoma. They pay attention to
      the value of some modern diagnostic methods including radioimmunological
      determination of the serum peptide hormone levels and some specific
      immunofluorescence assays with monoclonal antibodies.

PMID- 8255594
TI  - [Lucja Frey (1889-1943) in the 50th anniversary of her tragic death and 70th
      anniversary of the auriculotemporal syndrome].
AB  - Lucja Frey was a Polish neurologist born and lived in Lwow, former east Polish
      town, and died during the war in Lwow's ghetto. In 1923 she described the
      auriculo-temporalis syndrome, at present well known all over the world. But
      personality and history of the extraordinary Polish scientist remains obscure.
      The aim of this paper is to present her silhouette. Because a great number of
      Polish scientists are also not known abroad, the authors tried to explain the
      causes of their absence in the world bibliography.

PMID- 8255596
TI  - Doctor-lawyer questions tort reform article.

PMID- 8255595
TI  - [Alfred Marcin Sokolowski (1849-1924): an eminent physiatrist was he also a
      distinguished laryngologist? Should our medical textbooks be supplemented?].
AB  - This paper is the work on the distinguished Polish physician, pulmonologist,
      laryngologist Alfred Marcin Sokolowski (1849-1924), who was a ward head of
      internist department and chief of out-patients department in the St. Spirit
      Hospital in Warsaw. The scientific and professional activities in the area of
      laryngology of Sokolowski were presented. His achievements in the popularization
      of knowledge about laryngology are described. Sokolowski's education in
      laryngology in Warsaw, Heidelberg, Vienna, Paris and other places was strongly
      pointed out. In this paper many laryngological works and books are described, his
      activity in the many congresses is also depicted.

PMID- 8255597
TI  - Author offers follow-up to cult survey article.

PMID- 8255598
TI  - Finding the best response to health system reform: medical practice mergers.
AB  - Though specific legislation to revamp the nation's health care system may be more
      than a year away, health system reform has already impacted physician practices
      in a number of ways. This first in a series of two articles on finding the best
      response to health system reform overviews how practices have been affected and
      outlines physician considerations in merging practices.

PMID- 8255599
TI  - State Society expands managed care services.
AB  - All indicators surrounding the Clinton health care package point in one
      direction: managed care. But managed care, already a reality for many physicians
      involved in health maintenance organizations, preferred provider organizations,
      and point-of-service networks, has a myriad of meanings and facets. The Society
      is looking at every possible means to help members in these changing times.

PMID- 8255600
TI  - Retirement: getting it right the first time.
AB  - After a lifetime of being on call, retirement should be a snap. But getting to
      that state called "retirement" can be as hazardous as wading through an alligator
      infested swamp. Like anything else in life, retirement requires more preparation
      than meets the eye.

PMID- 8255601
TI  - Mistakes to avoid in recruiting a physician. The Health Care Group.

PMID- 8255602
TI  - Expanded AIDS case definition increases Pennsylvania's reported AIDS cases.
AB  - At the beginning of 1993, the Centers for Disease Control and Prevention adopted
      an expanded case definition of AIDS and a revision of the classification system
      for HIV infection for persons ages 13 years or older. This article explains the
      changes and their effects, defines the new system categories, and offers
      resources for physicians treating HIV-infected patients.

PMID- 8255603
TI  - Round two for physician-specific data due in December.

PMID- 8255604
TI  - Questioning the value of PROs: one more time.

PMID- 8255606
TI  - Considering ethical contrasts.

PMID- 8255605
TI  - Physician sets diabetes education as top priority.
AB  - Rachmel Cherner, MD, FACP, is an endocrinologist in private practice in
      Jenkintown, an active member of the Philadelphia County Medical Society, and a
      delegate to the State Society's House. He writes for Consultant magazine and
      serves on the staff of North Penn Hospital, and his work as a physician-educator
      was described in a Medical Economics publication called "Patient Satisfaction."
      In 1987, he established the Pavilion Diabetes Treatment Center.

PMID- 8255607
TI  - [The imidazoline receptor and the central regulation of arterial pressure].

PMID- 8255608
TI  - [Implication of tyrosine kinase p56lck in the activation of T lymphocytes].

PMID- 8255609
TI  - [Absence of distinctive characteristics between Staphylococcus epidermidis
      strains responsible of non-hospital infectious endocarditis and commensal
      strains].
AB  - In order to recognize particular characteristics of pathogenic strains,
      epidemiologic markers of 27 Staphylococcus epidermidis strains (9 pathological
      and 18 commensal) were studied. Nine strains were responsible of infective
      endocarditis (8 on native valves, and 1 on prosthetic valve). No case occurred
      after admission to hospital or surgery. Eighteen commensal strains were isolated
      from control subjects who had had no contact with the hospital environment and
      who had not received a recent antibiotic treatment. The microbiological
      characteristics were so diverse that no differentiation between the pathogenic
      strains and commensal strains could be done and no particular pathogenic clone
      was recognized.

PMID- 8255610
TI  - [Study of susceptibility of Haemophilus influenzae to beta-lactams by using HTM
      gelose (Haemophilus test medium)].
AB  - HTM agar was used for in vitro study of beta-lactam antibiotics activity on H.
      influenzae. Tested strains belong to the three ampicillin phenotypes: sensitive,
      betalactamase production and ampicillin resistance without production of
      betalactamase. Using 2 micrograms ampicillin disk, diameters > or = 20 mm and <
      20 mm separate ampicillin sensitive and resistant strains. The following zone
      size breakpoints could be suggested: ampicillin (10 micrograms) > or = 25 and <
      22 mm; amoxicillin (25 micrograms) > or = 26 mm and < 23 mm; ampicillin/sulbactam
      (10/10 micrograms) > or = 25 mm and < 22 mm; amoxicillin/clavulanic acid (20/10
      micrograms) > or = 26 mm and < 23 mm; cefaclor (30 micrograms) > or = 25 mm and <
      20 mm; cefuroxime (10 micrograms) > or = 22 mm and < 19 mm; cefixime (10
      micrograms) and cefpodoxime (10 micrograms) > or = 26 mm; cefotaxime (30
      micrograms) et ceftriaxone (30 micrograms) > or = 30 mm. The zone-size
      breakpoints concentrations, distribution of bacterial populations, mechanisms of
      resistance. In vitro study may screen for ampicillin resistance mechanisms.

PMID- 8255611
TI  - [Study of susceptibility of Haemophilus influenzae to antibiotics (other than
      beta-lactams) by using HTM gelose (Haemophilus test medium)].
AB  - HTM agar was used for in vitro study for antibiotics activity (other than beta
      lactams) on H. influenzae. Tested strains belong to various phenotypes. The zone
      size breakpoints were determined according to breakpoints concentrations,
      distribution of bacterial populations and mechanism of resistance. The following
      zone-size breakpoints could be suggested: chloramphenicol (30 micrograms) > or =
      28 and < 24 mm; kanamycin (30 UI) > or = 18 and < 15 mm; gentamicin (10 UI) > or
      = 16 and < 14 mm; tetracycline (30 UI) > or = 23 and < 18 mm; doxycycline (30 UI)
      > or = 20 and < 14 mm; minocycline (30 UI) > or = 20 mm; rifampicin (30
      micrograms) > or = 24 and < 20 mm; pristinamycin (15 micrograms) > or = 20 mm;
      erythromycin (15 UI) > or = 22 and < 18 mm; ciprofloxacin (5 micrograms) > or =
      30 mm; trimethoprim and co-trimoxazole > or = 24 and < 20 mm.

PMID- 8255612
TI  - [Sideroses of alveolar macrophages. Analysis of a continuous series of 360
      bronchoalveolar lavages].
AB  - 360 consecutive bronchoalveolar lavage fluids (BAL) were studied using semi
      quantitative method described by GOLDE (GOLDE score). 44 hemosiderosis were
      detected (12%). Most of them corresponded to massive alveolar hemorrhage (AH).
      Depending on pathological contexts, we distinguished three main groups of AH
      frequency: a group of high frequency (around 40%), an intermediate group (10%)
      and a low frequency group with less than 5%. Matching cytological results with
      clinical and radiological data, revealed that AH was often too late diagnosed
      because inconstancy of typical clinical and radiological signs. Even with a
      variable prognosis related to different physiopathological mechanisms, AH
      evolution is unpredictable. The authors suggest thus BAL cytological examination
      may systematically include a research of hemosiderosis in AH high frequency
      groups.

PMID- 8255613
TI  - [Activity of plasma dopamine-beta-hydroxylase in newborn infants. Implication in
      prematurity, maternal pathology and growth].
AB  - The aim of the study was to determine plasma dopamine-beta-hydroxylase activity
      (DBH) in newborn infants and possible changes with maturation, mode of delivery
      and maternal disease: pregnancy-induced hypertension and gestational diabetes.
      DBH activity was determined by high performance liquid chromatography from 82
      neonates divided in 2 groups: group I: 27 neonates (age: 1 to 8 days) including 6
      preterm and 21 full-term neonates; group II: 55 full-term neonates divided in 5
      classes: A: vaginal delivery; B: forceps; C: elective caesarean section; D:
      vaginal delivery and maternal hypertension; E: vaginal delivery and gestational
      diabetes. The plasma DBH activity was low in neonates and not influenced by
      prematurity. Significantly lower DBH activity was found after caesarean section.
      Hypertension and gestational diabetes did not affect umbilical cord plasma DBH
      activity.

PMID- 8255614
TI  - [The tyrosine kinases of the Src family: properties and roles in cells].
AB  - The protein tyrosine kinases (PTK) are implicated in cell proliferation
      processes. Furthermore, a number of viral oncogenes encode constitutively active
      variants of tyrosine kinases and several growth factor receptors possess
      intrinsic tyrosine kinase activity. The regulation and biological function of the
      kinase activity of Src family PTK are not yet well established. However, three of
      these kinases (src, yes and fgr) have been initially identified as products of
      viral oncogenes and a fourth (lck) is activated and overexpressed in certain
      lymphomas. In fact, several biological systems implicate and early and transient
      activation of Scr family PTK.

PMID- 8255615
TI  - [In vitro antibacterial activity of pristinamycin against penicillin resistant
      Streptococcus pneumoniae].
AB  - Pristinamycin, a member of streptogramin family, is the association of two groups
      (components I and pristinamycin II A) which have a high synergistic activity.
      Given the increasing rates of penicillin resistance in Streptococcus pneumoniae
      in many countries, and in particular of strains exhibiting multiple resistance to
      commonly used antibiotics, it was interesting to study the in vitro activity of
      pristinamycin against penicillin resistant S. pneumoniae (47 strains) and compare
      it with that of erythromycin. All strains were isolated from otitis media.
      Minimal inhibitory concentrations (MICs) were determined by an agar dilution
      technique using Mueller-Hinton medium supplemented with 5% horse blood. An
      inoculum of 10(4)-10(5) CFU per spot was delivered by a Steers replicator. This
      study showed that, among the 47 penicillin resistant strains, 29 (61.7%) were
      resistant to erythromycin but none of them were resistant to pristinamycin. The
      good in vitro activity of pristinamycin against S. pneumoniae could be of
      particular interest in cases of infections with multiresistant strains.

PMID- 8255616
TI  - [Evaluation of in vitro activity of pristinamycin against Haemophilus
      influenzae].
AB  - The activity of pristinamycin against H. influenzae was evaluated using various
      in vitro tests. Minimal inhibitory concentrations (MICs) were determined by an
      agar dilution method. The range of MICs was from 0.25 mg/l to 8 mg/l. MIC 50 was
      2 mg/l; MIC 90 was 4 mg/l. The activity of component pristinamycin II (PII) is
      similar to that of pristinamycin and superior to that of component pristinamycin
      I (PI). Minimal bactericidal concentrations (MBCs) were equal to or two times
      higher than MICs. Killing curves showed a bactericidal activity obtained after 6
      hours at MIC x 2 and MIC x 4 of pristinamycin. Component PII exhibited a
      bactericidal activity at MIC x 4. The post-antibiotic effect was high with
      pristinamycin: after two hours of contact with the antibiotic, PAEs were 2 hours
      with 1 mg/l, from 4 to 6.8 hours with 2 mg/l, and 6.7 hours with 4 mg/l. The PAEs
      with component PII were from 1 hour to 2 hours at concentrations of 1, 2, or 4
      mg/l. Antibiotic resistance to various antibiotics did not influence the
      antibacterial activity of pristinamycin. At a breakpoint < or = 2 mg/l, more than
      85% of the strains were sensitive to pristinamycin. The unimodal distribution of
      the strains showed the lack of acquired resistance to pristinamycin in these
      bacterial species.

PMID- 8255617
TI  - [Detection of hepatitis A virus by riboprobe labeled with digoxigenin: comparison
      of methods].
AB  - A riboprobe (RNA probe), corresponding to the 5' end of the HM175 hepatitis A
      virus (HAV) genome, was synthetized in vitro and was digoxigenin-labeled. Then
      the riboprobe was used to detect the CF53 HAV strain. Conditions of virus
      denaturation (with or without SDS and proteinase K, timing of assay) to release
      viral RNA were tested by dot-blot hybridization on a ten fold dilution of HAV
      suspension. Densitometric measures of dot-blot spots allowed to appreciate
      optimization of the method. Sensitivity of hybridization was compared with
      sensitivity of radioimmunoassay (RIA) and cell culture methods. Hybridization
      signals and scale of HAV suspension were consistent when 0.05% SDS, 0.17
      micrograms/ml Proteinase K, 37 degrees C, 30 mn or 3 hours are used. 8.10(2)
      TCID50 HAV was detected by hybridization with digoxigenin-labeled RNA probes.
      Detection threshold was the same as radioimmunoassay and lower comparatively to
      cell culture.

PMID- 8255618
TI  - Inguinal hernia and umbilical anomalies.
AB  - Inguinal hernias and umbilical anomalies remain the most common congenital
      anomalies. The loss of testis, ovary, or a portion of bowel from an irreducible
      hernia and the infectious complications of umbilical anomalies continue to be a
      threat to infants and young children. This article reviews the embryology,
      clinical features, and treatments of these anomalies and discusses some of the
      unusual and special considerations of these children.

PMID- 8255619
TI  - Scalp and neck masses.
AB  - The evaluation of head and neck masses involves an orderly approach based on a
      careful history and accurate physical examination. Additional information
      sometimes is necessary using appropriate laboratory and radiologic investigation.
      In the vast majority of cases, surgery for biopsy or removal of the mass is
      required. Accurate preoperative diagnosis may require evaluation by appropriate
      consultants to avoid unnecessary or inappropriate operations.

PMID- 8255620
TI  - The jaundiced newborn.
AB  - Evaluation of the newborn with hyperbilirubinemia is an important and commonly
      encountered problem in all clinical pediatric-based practices. Cholestatic
      jaundice is always pathologic and warrants prompt assessment. The timely
      evaluation and directed treatment of any jaundiced newborn are essential to
      prevent serious metabolic consequences and irreversible hepatic damage.

PMID- 8255621
TI  - Hemangiomas and vascular malformations of infancy and childhood.
AB  - The vast majority of vascular anomalies of infancy and childhood can be
      biologically classified as hemangioma or vascular malformation. Hemangiomas are
      benign neoplasms that proliferate rapidly in infancy only to involute in early
      childhood. The majority of hemangiomas do not need treatment. Pharmacologic
      therapy, with corticosteroids or interferon-alpha-2a, is indicated for lesions
      that threaten vital function or are grossly deforming. Vascular malformations are
      not tumors, but rather vessel abnormalities due to errors of vascular
      morphogenesis. They derive from embryonal capillary, venous, arterial, or
      lymphatic channels, or combinations thereof. The appearance, clinical behavior,
      and therapy differ based on their channel types. All too often, unfortunately,
      children with vascular anomalies are shuffled from physician-to-physician because
      a single practitioner, even a specialist, does not have sufficient knowledge to
      properly treat the vascular lesion. The authors recommend that every major
      referral center have a multidisciplinary "Vascular Anomalies Team." We also
      endorse a biologic classification of vascular lesions to facilitate
      interspecialty communication regarding diagnosis, natural history, and therapy.

PMID- 8255622
TI  - The right lower quadrant "revisited".
AB  - Appendicitis remains a common and morbid illness in children. The history,
      epidemiology, pathophysiology, clinical presentation, diagnostic evaluation, and
      management of acute appendicitis are discussed in this article.

PMID- 8255623
TI  - Inflammatory bowel disease.
AB  - Inflammatory bowel disease in children encompasses at least two forms of
      intestinal inflammation: ulcerative colitis and Crohn's disease. These two
      disease processes are differentiated based on clinical presentation, radiologic
      findings, endoscopic findings, histologic evaluation, and exclusion of
      alternative causes. The treatment and operative interventions are reviewed.

PMID- 8255624
TI  - Gastroesophageal reflux in children.
AB  - Operations for the control of complicated gastroesophageal reflux in children are
      commonly performed procedures in large pediatric centers. The comprehensive
      diagnostic scheme includes radiologic and endoscopic work-up coupled with
      extended pH probe analysis. Medical therapy remains the principle form of
      management, with surgery reserved for treatment failure.

PMID- 8255625
TI  - Abdominal tumors in infancy and childhood.
AB  - Detection of an abdominal mass in a child is an alarming finding for both parent
      and practitioner. Diagnostic studies including ultrasonography, computed
      tomography, and magnetic resonance imaging provide an accurate diagnosis in most
      cases. The current treatment of Wilms' tumor results in an 85% to 90% survival.
      Hepatoblastoma and neuroblastoma often present in an advanced stage and require
      preoperative chemotherapy before resection is attempted. Improved survival for
      children with these tumors awaits better detection, chemotherapy, and
      understanding of the biology of their growth.

PMID- 8255626
TI  - Newborn surgical emergencies. Gastrointestinal anomalies, abdominal wall defects.
AB  - Structural anomalies of the gastrointestinal tract and anterior abdominal wall
      diagnosed in the perinatal period often require prompt surgical intervention.
      This article highlights the pathophysiology, evaluation, and management of the
      more common lesions encountered in the neonate.

PMID- 8255627
TI  - Newborn surgical emergencies. Congenital diaphragmatic hernia and extracorporeal
      membrane oxygenation.
AB  - Bochdalek hernia is a posterolateral defect in the embryogenesis of the
      diaphragm. Abdominal contents enter the thorax during fetal development and
      result in pulmonary hypoplasia. A cause of respiratory distress in the newborn,
      the management of this disease has undergone dramatic changes. The defect
      requires surgical repair, but success depends more on preoperative and
      postoperative management of the associated physiologic derangements.

PMID- 8255628
TI  - Management of the short bowel syndrome in the pediatric population.
AB  - The short bowel syndrome in the pediatric population most commonly results from
      neonatal necrotizing enterocolitis. Multiple remedial surgical procedures have
      been developed to manage the rapid intestinal transit, decreased mucosal surface
      area, ineffective peristalsis, and short intestinal length in these patients.
      Despite significant morbidity, the overall outcome is favorable and warrants
      aggressive nutritional support, medical management, and surgical intervention in
      selected patients.

PMID- 8255629
TI  - Birth trauma.
AB  - Although significant birth injury accounts for few neonatal deaths and stillborns
      in the United States, it still occasionally and unavoidably occurs. This article
      reviews soft tissue, peripheral nerve, intrathoracic, and intra-abdominal injury.

PMID- 8255630
TI  - Pediatric trauma. Prevention strategies.
AB  - Injury is the most important threat to the health of children in the United
      States and the leading cause of death after the first year of life. Injuries must
      be viewed as diseases that can be prevented by using principles of epidemiology,
      engineering, biomechanics, and health education. Effective preventative
      strategies coupled with improvements in access and delivery of pediatric trauma
      care can reduce the tremendous toll on children.

PMID- 8255631
TI  - Parental childhood respiratory illness and respiratory illness in their infants.
      Group Health Medical Associates.
AB  - Parental histories of childhood respiratory trouble (CRT) were examined as risk
      factors for lower respiratory tract illnesses in healthy infants enrolled in the
      Children's Respiratory Study, Tucson, Arizona. A parental history of childhood
      respiratory trouble before age 16 was a risk factor for infantile lower
      respiratory tract illnesses (LRIs). Early age of onset of the parental CRT and
      those illnesses described as asthma or bronchiolitis showed the greatest risk:
      odds ratio = 2.8, P < 0.05. After controlling for known and suspected
      confounders, a parental history of CRT described as asthma or bronchiolitis with
      onset before age 3 was associated with wheezing LRIs in their children, with an
      odds ratio of 2.6, P < 0.05. A parental history of CRT described as
      bronchitis/croup was associated with nonwheezing LRIs in their children: odds
      ratio = 2.2, P < 0.05. These findings suggest a familial component to childhood
      respiratory trouble which may have a hereditary basis.

PMID- 8255632
TI  - Effects of sidestream smoke exposure and age on pulmonary function and airway
      reactivity in developing rats.
AB  - Children exposed to environmental tobacco smoke (ETS) in their homes have
      increased cough, respiratory illness, airway obstruction, and hyperreactivity.
      Since an animal model is needed to understand the mechanism by which this occurs,
      our study was designed to determine if immature rats develop airway obstruction
      and increased airway reactivity when exposed to sidestream smoke (SSS, respirable
      suspended particulate concentration 1.00 +/- 0.03 mg/m3, CO concentration 6.48 +/
      0.29 ppm). In the first of 3 studies, rats were exposed to filtered air (FA) or
      SSS for 6 hr/day, 5 days/week from day 2 to week 8 or week 15 of life (n = 6-8 in
      each group). SSS exposure did not change lung resistance (RL), dynamic lung
      compliance (CLdyn), lung weight/body weight ratio (LW/BW), pulmonary artery
      pressure (PPA), body weight, or airway reactivity to methacholine (all P > 0.2, 2
      way ANOVA). Regardless of exposure, lungs from younger rats were relatively
      heavier and more reactive to methacholine than lungs from older rats (P < 0.05, 2
      way ANOVA). In the second study, 15-week-old rats were exposed to FA or SSS for 3
      hr or for 4 days (6 hr/day, n = 6 in each group). SSS exposure again had no
      effect on CLdyn, RL, LW/BW, PPA, or airway reactivity to methacholine (all P >
      0.2, ANOVA). In the third study, rats were exposed to FA or SSS from day 2 to
      week 11 of life (n = 7 in each group). SSS exposure reduced airway (P = 0.004)
      but not pulmonary artery (P = 0.63) reactivity to serotonin.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8255633
TI  - Regional distribution of myosin heavy chain isoforms in rib cage muscles as a
      function of postnatal development.
AB  - We studied the expression of myosin heavy chain (MHC) isoforms, utilizing
      electrophoretic methods, in rib cage (RC) muscles: the scalenus medius, the
      parasternal, cephalic, midthoracic, and caudal intercostal muscles; and in the
      diaphragm (DI) of rats during postnatal development and when mature. At day 1,
      all RC muscles and the DI expressed MHC neonatal/embryonic (69-92% of total MHC
      complement) with little MHC slow and 2A; the RC muscles alone expressed a small
      proportion of MHC 2B (2-4%). On day 4, MHC neonatal/embryonic expression still
      predominated (55-71%) but increased MHC 2A expression was observed in both the RC
      (11-21%) and DI (31%); MHC 2B (5-7%) was noted in the RC muscles but not the DI.
      By day 14, MHC neonatal/embryonic and 2A expression each comprised a third of the
      total MHC complement of the RC muscles, MHC 2X was first observed, and MHC 2B
      expression increased. The day 14 DI was comprised of equal proportions of MHC
      neonatal/embryonic, slow and 2A with little MHC 2X (11%). The adult and day 30
      animals expressed comparable muscle-specific MHC phenotypes: the DI characterized
      by a proportional mixture of MHC slow, MHC 2A, and MHC 2X, with little MHC 2B,
      whereas the RC muscles expressed predominantly MHC 2B (40-62%). We conclude that
      the RC muscles and DI show comparable MHC phenotypes in the immediate newborn
      period but differ in their MHC expression during postnatal development and when
      mature. The RC muscles show only minor intermuscle variations in MHC phenotype
      during development, and when mature are characterized by fast MHC isoform
      expression, particularly MHC 2B.

PMID- 8255634
TI  - Low-frequency vs. high-frequency respiratory mechanics after methacholine
      challenge in artificially ventilated rabbits.
AB  - Respiratory system resistance (Rrs) and elastance (Ers) were estimated by two
      methods, before and after methacholine in six anesthetized, paralyzed, and
      artificially ventilated rabbits. Rrs and Ers were obtained (1) by multiple linear
      regression analysis of the relationship between tracheal pressure and tidal
      volume and flow [Rrs(mlr)], Ers(mlr), and (2) by analysis of the Fourier
      transforms of tracheal pressure and flow resulting from 4 to 30 Hz pseudorandom
      pressure oscillations delivered by an Infant Star respirator [Rrs(os), Ers(os)].
      Rrs(os) was significantly lower than Rrs(mlr). For instance, Rrs(os) at 20 Hz
      [Rrs(os)20] was (mean +/- SD) 17.3 +/- 3.5 vs 21.4 +/- 3.6 cm H2O x L-1 x s (P <
      0.01) for Rrs(mlr). Ers(os) was significantly higher than the respective value
      obtained by multiple linear regression (718.2 +/- 81.0 vs 403.7 +/- 43.0 cm H2O L
      1; P < 0.01). After methacholine, the changes of respiratory mechanics were
      similar with both methods. Rrs(mlr) and Rrs(os)20 increased respectively by 131
      +/- 45 and 134 +/- 76%, and Ers(mlr) and Ers(os) increased respectively by 63 +/-
      7 and 54 +/- 13%. A significant correlation was observed between Rrs(mlr) and
      Rrs(os)20 (r = 0.97) and between Ers(mlr) and Ers(os) (r = 0.96). We conclude
      that positive response to methacholine may be detected by forced oscillation as
      well as by multiple linear regression. However, the identified physiological
      components of the lung response (alteration in lung viscoelastic properties,
      increased lung inhomogeneity or increased intrathoracic airway shunt) are likely
      to be different with each method.

PMID- 8255635
TI  - Effect of amrinone during group B Streptococcus-induced pulmonary hypertension in
      piglets.
AB  - Intravenous infusion of group B Streptococcus (GBS) into neonatal animals
      produces pulmonary hypertension, ventilation/perfusion (VA/Q) mismatch, and an
      increase in serum levels of thromboxane B2 (TxB2) and tumor necrosis factor (TNF)
      alpha. The vasodilator amrinone (amr) is a cGMP-inhibited phosphodiesterase
      inhibitor and is reported to inhibit thromboxane A2 and TNF production. We
      hypothesized that infusion of amr would cause pulmonary vasodilation and reduce
      serum TxB2 and TNF levels in piglets with late phase GBS-induced pulmonary
      hypertension. The effect of amr on gas exchange was also determined. A continuous
      infusion of GBS was administered for 5 hr to 4 groups of anesthetized,
      mechanically ventilated neonatal piglets. An amr bolus of 8 mg/kg was given at 4
      hr followed by a 1 hr continuous infusion of either 10 or 20 micrograms/kg/min of
      amr (amr 10 and amr 20, respectively). Control piglets received a bolus and 1 hr
      infusion of amr carrier. The infusion of amr, but not of carrier reversed late
      phase GBS-induced pulmonary hypertension. Piglets infused with amr 20 showed
      transient selective pulmonary vasodilation, based on a reduced ratio of pulmonary
      to systemic vascular resistance (PVR/SVR ratio) value at 30 min but not at 1 hr,
      compared to pre-amr treatment values. The PVR/SVR ratio values for amr 10 and
      control group did not change after treatment with either amr or carrier.
      Treatment with amr 10 or 20 did not decrease serum TxB2 or TNF levels or increase
      VA/Q mismatch.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255636
TI  - Comparison of efficacy of salbutamol and sodium cromoglycate in the prevention of
      ticarcillin-induced bronchoconstriction.
AB  - Nebulized ticarcillin can cause bronchoconstriction in children with cystic
      fibrosis (CF). We assessed whether pretreatment with salbutamol or sodium
      cromoglycate (SCG) would prevent this side-effect using a randomized, double
      blind, placebo-controlled design. Fifteen children with CF received pretreatments
      of saline, SCG, or salbutamol, in random order, one on each day. Baseline lung
      function was measured before and after pretreatment, and after ticarcillin
      nebulization. On the control day (saline pretreatment), ticarcillin caused a
      reduction in forced expiratory volume in one second (FEV1), which was maximal 10
      minutes after receiving the aerosol and persisted for 120 minutes. The mean
      maximal fall in FEV1 was 9%. Pretreatment with salbutamol abolished the fall in
      FEV1 seen with ticarcillin at all time points. Pretreatment with SCG diminished
      the maximal fall in FEV1 at 10 minutes (mean, 4%) and resulted in the FEV1
      returning to baseline within 120 minutes. These data suggest that pretreatment
      with salbutamol is more effective in preventing ticarcillin-induced
      bronchoconstriction in the doses used in routine clinical practice, than it is
      with SCG.

PMID- 8255637
TI  - The effect of instrumental dead space on measurement of breathing pattern and
      pulmonary mechanics in the newborn.
AB  - The effect of the instrumental dead space on breathing pattern and the values of
      pulmonary mechanics was evaluated because of concern about the relatively large
      dead space of 26 mL in a commercially available system. Sixty-three healthy
      newborn infants were studied with a system as commercially supplied, and with the
      dead space eliminated using a 2 L/min biased flow. This led to a significant
      reduction in mean (+/- SD) values of respiratory rate from 56.8 (+/- 11.7) to
      48.2 (+/- 11.7) breath/min (P < 0.0001), tidal volume from 5.2 (+/- 1.3) to 4.9
      (+/- 0.9) mL/kg (P < 0.05), minute volume from 284 (+/- 68) to 220 (+/- 63)
      mL/min/kg (P < 0.0001), and work of breathing from 13.7 (+/- 6.6) to 11.8 (+/-
      7.6) g.cm/kg (P < 0.02). There was a significant increase in dynamic lung
      compliance from 5.2 (+/- 1.5) to 5.6 (+/- 1.2) mL/cm H2O (P < 0.01) but no
      difference for total pulmonary resistance 39.6 (+/- 22.8) and 38.8 (+/- 22.2) cm
      H2O/L/sec. This shows that the instrumental dead space prevents measurement of
      the basal breathing patterns and alters the values of pulmonary mechanics. It is,
      therefore, important to use equipment with low dead space or make efforts to
      remove it by using a biased flow system such as we describe when measuring
      breathing patterns and pulmonary mechanics in the newborn.

PMID- 8255638
TI  - Bronchogenic cyst associated with left lower lobe bronchiectasis.

PMID- 8255639
TI  - Munchausen's syndrome presenting as cystic fibrosis with hemoptysis.

PMID- 8255640
TI  - Types and complications of femoral neck fractures in children.
AB  - This multicenter collaborative study was undertaken to review the types and
      complications of femoral neck fractures in children. It is a retrospective
      clinical and radiological review of 108 femoral neck fractures. Cases originated
      from four different pediatric hospitals. All the patients had plain radiographs.
      Fractures occurred at all ages (one day to 18 years), and 63% of the patients
      were boys. Forty-nine fractures were traumatic; 37 were pathologic, 19 were
      insufficiency fractures; and three were fatigue fractures. Unless the underlying
      bone was abnormal, significant high velocity trauma, fall from a height or other
      severe violence was required to fracture the femoral neck. A unicameral bone cyst
      was the underlying lesion in 40% of pathologic femoral neck fractures and
      malignancy in 35%. Osteoporosis as in myelodysplasia, osteogenesis imperfecta and
      from other causes was responsible for 52% of insufficiency fractures. Because of
      the unique osseous and vascular anatomy of the femoral head and neck in the
      growing child, these fractures have a high incidence of complications.
      Complications included avascular necrosis 13%, premature closure of the
      epiphyseal plate 12%, varus deformity 8.3%, and nonunion 3.7%. Unless there is a
      clear history of significant violence, a cause for a femoral neck fracture should
      be sought, e.g. an underlying bone lesion or a metabolic bone disease. These
      fractures are rare, but are serious injuries since their complications may lead
      to a life-long disability.

PMID- 8255641
TI  - Physeal and epiphyseal extent of primary malignant bone tumors in childhood.
      Correlation of preoperative MRI and the pathologic examination.
AB  - Twenty-two patients with metaphyseal primary malignant bone tumors (17
      osteosarcomas, 5 Ewing's tumors) occurring before closure of the growth plate
      were examined with plain radiographs and MRI in order to determine the physeal or
      epiphyseal extent of the tumor. Results were correlated with the pathologic
      examination. Transphyseal spread was pathologically proven in 13 cases (59%): 12
      cases of osteosarcoma and 1 case of Ewing's tumor (70% and 20%, respectively).
      There was no significant relation between epiphyseal invasion, age of patient,
      length of tumor or, in the cases of osteosarcoma, response to chemotherapy. Plain
      radiographs showed epiphyseal involvement in 4 cases and there were 10 false
      negatives. MRI revealed epiphyseal involvement in all cases; there were no false
      positives or false negatives. T1-weighted images in coronal or sagittal planes
      appeared to be sufficient. These findings are very useful in planning surgical
      limb salvage procedures and stress the ineffectiveness of the "barrier effect" of
      the growth plate against tumor spread.

PMID- 8255643
TI  - MRI evaluation and follow-up of bone necrosis after meningococcal infection and
      disseminated intravascular coagulation.
AB  - Disseminated intravascular coagulation (DIC) is a serious complication of
      meningococcal septicaemia. It often results in infarction of various tissues
      namely the skin, adrenal glands, kidneys, brain and, much less commonly, bones.
      We describe a patient who presented bone lesions after meningococcal septicaemia.
      In addition to plain radiography and scintigraphy the lesions were evaluated with
      MRI and have proved to be extensive and still progressive, approximately 18
      months after the onset of the disease.

PMID- 8255642
TI  - MRI evaluation of superficial soft tissue lesions in children.
AB  - The role of MRI in the evaluation of superficial soft tissue lesions in children
      has not been well established. We present our experience with MRI in the
      evaluation of nineteen children with a variety of cutaneous and subcutaneous
      lesions. We find MRI to have a definite role in the evaluation of these lesions
      particularly when determining extent or depth of involvement would affect medical
      or surgical management. MRI has a less well defined role in tissue determination.
      Spin echo T1 and T2 weighted images were sufficient for evaluation in most cases.
      Fat suppression images added additional information in fatty tumors. The MRI
      appearance of juvenile hyaline fibromatosis and lipoblastomatosis has not been
      previously described and is included in this study.

PMID- 8255644
TI  - Orofacial abscesses of odontogenic origin in the pediatric patient. Report of two
      cases.
AB  - Odontogenic infections rarely spread beyond the periapical space. Occasionally
      spread of infection into contiguous anatomic areas occurs through bone, fascial
      or muscular barriers. Two cases of orofacial abscess of odontogenic origin in the
      pediatric patient are presented, one imaged with CT and the other with MRI. Both
      abscesses involved the deep and superficial tissues of the face. Additionally,
      one of the abscesses extended into the orbit and the other involved the preseptal
      soft tissue. The pathogenesis, mechanism of spread and management of the disease
      are discussed.

PMID- 8255645
TI  - Iron deposition in cranial bone marrow with sickle cell disease: MR assessment
      using a fat suppression technique.
AB  - Thirteen patients with sickle cell disease (SCD) undergoing transfusion therapy
      and 8 control patients were examined by magnetic resonance imaging to
      discriminate bone marrow change due to iron deposition from hematologic marrow
      hyperplasia. Using T1-weighted spin echo images, only two subjects showed
      extremely low signal intensity marrow compatible with iron deposition. However,
      using T2-weighted fast spin echo images with fat suppression, cranial bone marrow
      in SCD patients with transfusion therapy showed considerably lower signal than
      that of controls. The main cause of marrow signal decrease in SCD patients with
      transfusion therapy was considered to be iron deposition due to repeated
      transfusion therapy rather than red marrow hyperplasia.

PMID- 8255646
TI  - Optimizing conventional cardiac MRI in the rabbit at 0.3 T.
AB  - The aim of this study was to define the most efficient way of performing cardiac
      MRI for anatomic information in small experimental animals, using a vertical
      magnetic field with a strength of 0.3 T (FONAR beta-3000M). This information may
      be used to improve cardiac MRI in infants and small children, since the size of a
      rabbit is considered comparable to that of a neonate. Experimental axial cardiac
      MRI studies were performed in a rabbit under general anesthesia in order to study
      the effects on image quality of changing various imaging parameters. These are
      ECG-gating, number of excitations (averages), number of warp levels, echo time
      (TE) and repetition time (TR). The effects of changing the size of the field of
      view (FOV), the slice thickness and the phase-encoding direction were also
      studied. We found that ECG-gating was crucial and that three excitations, TE 16
      ms, and 257 vertical phase-encoding warp levels were adequate. Five-millimeter
      slice thickness and FOV 20 cm were preferred.

PMID- 8255647
TI  - Short stature, mental retardation, craniosynostosis, Klippel-Feil syndrome,
      Scheuerman kyphosis, rib gaps and other distinctive skeletal and genital
      anomalies. A new syndrome?

PMID- 8255648
TI  - Micromelic dwarfism--humerus, femur, tibia type. Report of a case.
AB  - A 12.5-year-old girl with severe micromelic dwarfism and characteristic
      radiographic findings is reported. The most important phenotypic abnormality was
      dwarfism (stature < 100 cm); the patient had a normal face and intelligence. The
      diagnostic radiographic findings were those of spondylo-epimetaphyseal dysplasia
      characterized by severe shortening of humerus, femur and tibia, hypoplastic but
      normal-shaped fibula, ulna and radius, uniform shortening of the short tubular
      bones and moderately severe platyspondyly. These radiographic changes were
      already present at birth, which should make it possible to recognize the disease
      in the newborn. We propose naming this disorder micromelic dwarfism-humerus,
      femur, tibia type.

PMID- 8255649
TI  - Osteosclerotic metaphyseal dysplasia.
AB  - A new sclerosing bone disease in two Japanese siblings born to first-degree
      cousin parents is reported. Clinically the disease is characterized by early
      developmental delay, hypotonia and later spastic paraplegia. The unique
      radiographic changes consist of peripheral osteosclerosis affecting predominantly
      metaphyses of the long bones and to a lesser degree ends of the ribs and
      clavicles, iliac crests, acetabulae, ischio-pubic synchondroses and vertebrae.
      The epiphyses are sclerotic in early life. The round bones, short tubular bones
      and the skull are little affected. The shafts of the tubular bones are
      osteopenic. Increased serum alkaline phosphatase was the only laboratory
      abnormality detected. We suggest the name "osteosclerotic metaphyseal dysplasia"
      for this disorder.

PMID- 8255650
TI  - ACTH induced adrenal enlargement in infants treated for infantile spasms and
      acute cerebellar encephalopathy.
AB  - ACTH is used in childhood to treat infantile spasms and acute cerebellar
      encephalopathy (opsoclonus-cerebellar ataxia syndrome). We report two infants
      with ultrasonographic and CT evidence of massive, reversible adrenal enlargement
      secondary to exogenous ACTH therapy for these disorders.

PMID- 8255651
TI  - Adrenal hemorrhage complicating ACTH therapy in Crohn's disease.
AB  - Huge dose ACTH therapy is used in some severely ill patients with inflammatory
      bowel disease. We report a teenage girl with Crohn's disease who developed an
      acute abdomen following ACTH therapy. CT revealed the mass to be a hemorrhagic
      adrenal gland; the opposite adrenal gland was hypertrophied but without signs of
      hemorrhage.

PMID- 8255652
TI  - Chronic intoxication by ethane-1-hydroxy-1,1-diphosphonate (EHDP) in a child with
      myositis ossificans progressiva.
AB  - A child with myositis ossificans progressiva was treated for 8 years with ethane
      1-hydroxy-1,1-diphosphonate (EHDP) 30-40 mg/kg per day. Latterly he complained of
      severe, progressive bone and joint pain which made standing and walking almost
      impossible. A radiographic skeletal survey showed diffuse ricket-like lesions.
      Withdrawal of EHDP therapy produced substantial improvement in his general
      condition as well as in the radiographic appearance of the bones. Multiple
      exostoses were observed in this case and, particularly those around the knees,
      presented a peculiar morphology. This supports the theory that exostoses
      originate from a defect of metaphyseal modelling.

PMID- 8255653
TI  - Multifocal primary neuroblastoma.
AB  - The purpose of this study is to present three patients with multifocal primary
      neuroblastoma, to review the literature, and describe the radiographic findings.
      SUBJECTS AND METHODS: Three children with multifocal neuroblastoma have been
      identified. The case histories and imaging findings in these patients are
      reviewed. RESULTS: Two children had synchronous and one child had metachronous
      multifocal primary neuroblastoma. The primary tumors were both in the abdomen in
      one patient, both in the chest in another patient, and in the chest and abdomen
      in the third patient. Evidence for multifocal origin of these tumors, rather than
      metastatic spread, is presented. CONCLUSION: Multifocal primary neuroblastomas
      can occur. The tumors maybe synchronous or metachronous. Awareness of this
      disorder may prevent errors in diagnosis and staging. Although not identified in
      our patients there is a strong familial incidence of neuroblastomas in those
      patients with multifocal tumors.

PMID- 8255654
TI  - A complete ileo-tumor-colic fistula in a child with Burkitt's lymphoma.
AB  - A boy with abdominal Burkitt's lymphoma developed rectal bleeding, abdominal
      distension, pain, and fever three weeks after diagnosis. Imaging studies revealed
      a necrotic tumor mass allowing a fistulous pathway from the ileum to the proximal
      colon. A laparotomy was performed, with resection of the large necrotic tumor.
      The child recovered, and has had no further evidence of Burkitt's disease. The
      radiological evaluation performed in this case ensured proper medical management
      and surgical intervention during a life-threatening event. The possibility of
      bowel perforation as a complication of therapy for abdominal lymphoma must be
      recognized.

PMID- 8255655
TI  - Infiltrating lipoma of the chest wall.

PMID- 8255656
TI  - Visualization of enlarged mesenteric lymph nodes at US examination. Clinical
      significance.
AB  - PURPOSE: To identify conditions associated with enlarged mesenteric lymph nodes
      in children with acute abdominal pain and determine the ability of US to detect
      associated abnormalities. METHODS: Two hundred and fifty children with acute
      abdominal pain were evaluated for the presence of enlarged mesenteric lymph nodes
      (AP diameter > 4 mm). Additionally, a reference group of 50 asymptomatic children
      was also studied for the presence of enlarged mesenteric lymph nodes. RESULTS:
      Enlarged mesenteric lymph nodes were noted in 35 (14%) symptomatic children and
      two (4%) asymptomatic children. A specific diagnosis was established in 16/35
      (46%) symptomatic children with mesenteric lymphadenopathy. Acute appendicitis
      was the most common diagnosis. The discharge diagnosis in the remaining 19
      children was abdominal pain or gastroenteritis of unknown origin. US suggested
      the correct diagnosis in 12/16 (75%) children in whom a definite diagnosis was
      established. Histopathologic examination of enlarged mesenteric lymph nodes in
      three patients demonstrated non-specific inflammatory changes. CONCLUSION:
      Enlarged mesenteric lymph nodes in children with acute abdominal pain represents
      a nonspecific finding. Mesenteric lymphadenopathy is associated with a variety of
      medical and surgical conditions in symptomatic children and is occasionally seen
      in asymptomatic children. Sonography is useful in establishing a primary
      diagnosis in these children.

PMID- 8255657
TI  - Torsion of wandering spleen: the whorled appearance of the splenic pedicle on CT.
AB  - Congenital deficiency or acquired laxity of the suspensory ligaments of the
      spleen may result in extreme splenic mobility. This rare condition, which is
      termed wandering or ectopic spleen predisposes the elongated splenic pedicle to
      torsion. We present a case of splenic torsion with a new CT finding consisting of
      a whorled appearance of the splenic pedicle. To our knowledge this finding has
      not been described before.

PMID- 8255658
TI  - Ultrasound grading of hydronephrosis: introduction to the system used by the
      Society for Fetal Urology.
AB  - The Society for Fetal Urology (SFU) was founded in 1988 to study the postnatal
      evolution of prenatally detected anomalies of the urinary tract by following
      those neonates whose prenatal studies have brought them to medical attention
      while asymptomatic. The SFU has attempted to standardize methods of performing
      and grading the ultrasound and radionuclide examinations in this population. A
      system to grade upper tract dilatation or hydronephrosis (HN) imaged by
      ultrasound has been developed and is being used by SFU members in 36
      institutions. The appearance of the calices, renal pelvis and renal parenchyma
      are key in determining the grade of HN and are illustrated in this article.

PMID- 8255659
TI  - Acute scrotum in an infant: post-herniorrhaphy complication. Sonographic
      evaluation.
AB  - The complications of herniorrhaphy mainly involve hematoma and other fluid
      collections within the scrotum. Discussed here is a case of another post
      herniorrhaphy complication, recurrent scrotal hernia, in an infant who presented
      with an acute scrotum and was evaluated sonographically.

PMID- 8255660
TI  - Testicular torsion: missed diagnosis on colour Doppler sonography.
AB  - Colour Doppler sonography is of value in diagnosing scrotal pathology. We report
      a case of testicular torsion misdiagnosed as a paratesticular tumour by colour
      Doppler sonography and highlight some of the pitfalls involved in this technique.

PMID- 8255661
TI  - The value of baseline CT head scans in the assessment of shunt complications in
      hydrocephalus.
AB  - The purpose of this study was to determine the value of a baseline CT head scan
      in the assessment of patients who subsequently presented with symptoms which may
      have been due to shunt complications (such as blockage or infection). In all
      these patients the shunt had been inserted in the treatment of hydrocephalus. We
      conclude that the presence of a baseline scan does not add to the interpretation
      of CT scans done when the patient presents with symptoms of possible shunt
      malfunction.

PMID- 8255662
TI  - Neuroimaging of Rasmussen's encephalitis.
AB  - A case of Rasmussen's encephalitis is reviewed. Focal seizures and hemiparesis in
      a 5-year-old child progressed over a period of 2 1/2 years. Neuroimaging findings
      showed progressive atrophy of the right temporal lobe. The diagnosis of this
      syndrome is possible using a combination of the clinical symptoms and
      neuroimaging findings.

PMID- 8255663
TI  - Tuberous sclerosis associated with pachygyria. CT findings.
AB  - The case is presented of a 1.5-year-old with the typical CT features of tuberous
      sclerosis and pachygyria, in combination. Tuberous sclerosis was evidenced by
      multiple subependymal calcifications, and pachygyria by the relevant CT
      appearances. Periventricular heterotopia and total callosal agenesis were
      associated findings. The findings in this patient convincingly suggest a close
      relationship between tuberous sclerosis and pachygyria, although the case is the
      first to be reported in the literature.

PMID- 8255664
TI  - Gyriform calcifications following purulent meningitis.
AB  - The case is presented of an 8-month-old boy who developed gyriform calcifications
      in the parieto-occipital region 5 months after purulent E. coli meningitis.
      Subcortical calcifications were also evident, and the entire region was
      contracted. It is apparent that severely damaged parenchyma due to purulent
      meningitis can produce cortical/subcortical calcifications.

PMID- 8255665
TI  - Aspergillosis in children with acquired immune deficiency.
AB  - Two children are presented with AIDS and aspergillosis. One child had pulmonary
      involvement while the other had invasion of the skull and brain. The rarity of
      aspergillosis in AIDS patients is discussed as well.

PMID- 8255666
TI  - American Pediatric Society Presidential Address 1993: the fetal frontier.

PMID- 8255667
TI  - Society for Pediatric Research Presidential Address 1993: development of the
      academic pediatrician.

PMID- 8255668
TI  - The molecular genetics of pediatric lipid disorders: recent progress and future
      research directions.
AB  - Over the last 10 years, the explosion of molecular biology and molecular genetic
      techniques have allowed major advances in the diagnosis and management of a wide
      variety of human disorders. These range from accurate and simple screening for
      carriers of thalassemia (Old JM, Varawalla NY, Weatherall DJ: Lancet 2:834-837,
      1990) to the use of preimplantation diagnosis of embryos at risk for untreatable
      congenital defects (Monk M, Holding C: Lancet 1:985-988, 1990) and the
      development of gene therapy for treatment of disorders such as adenosine
      deaminase deficiency (Sharp D: Lancet 1:1277-1278, 1991). These same molecular
      techniques have also been applied to pediatric lipid disorders with some notable
      successes, both in their diagnosis and understanding the mechanisms of the
      resulting pathology, including the recent experiments (Wilson JM, Grossman M, Wu
      CH, Chowdhury NR, Wu GY, Chowdhury JR: J Biol Chem 267:963-967, 1992) that have
      led to proposals to treat homozygous familial hypercholesterolemia by gene
      therapy. The purpose of this review is to detail this molecular genetic progress
      for two of the disorders that result in disturbed triglyceride metabolism in
      infants, lipoprotein lipase deficiency and apo CII deficiency, and four disorders
      that lead to disturbed cholesterol levels in infancy, abetalipoproteinemia,
      hypobetalipoproteinemia, familial defective apo B, and familial
      hypercholesterolemia. We will also address the question of how knowledge of the
      mutation causing the defect in a particular patient could be clinically useful
      and highlight areas of research for the future.

PMID- 8255669
TI  - Developmental and tissue-specific modulation of rat galactose-1-phosphate
      uridyltransferase steady state messenger RNA and specific activity levels.
AB  - To assess the role of genetic regulation as a modulating factor in the
      variability of rat tissue galactose-1-phosphate uridyltransferase (GALT) sp act,
      we have determined steady state GALT mRNA and sp act in rat liver during
      postnatal development. Steady state GALT mRNA levels increase from birth to d 5
      and subsequently decrease toward adult levels. GALT sp act mirrors the mRNA
      pattern. A survey of steady state mRNA and GALT sp act of several adult rat
      tissues revealed marked tissue differences with a good correlation of the two
      parameters. Liver had the highest GALT mRNA and sp act; kidney, ovary, and heart
      had similar but lower mRNA and sp act; skeletal muscle and testes had the least
      GALT mRNA and enzyme sp act. These findings suggest that genetic regulation is
      important in the variable expression of GALT tissue sp act.

PMID- 8255670
TI  - Purification of fibroblast-derived celiac disease autoantigen molecules.
AB  - We have recently purified autoantigen polypeptides reacting with celiac disease
      patient sera IgA from the extracellular noncollagenous matrix compartment of
      fetal lung tissue. These molecules trigger the production of different tissue
      antibodies, the so-called antireticulin and antiendomysium antibodies in celiac
      disease. In the present report, we show that fibroblasts synthesize and secrete
      celiac disease autoantigen molecules. The secretion product, reactive with IgA
      from celiac disease patients, is a large-molecular-weight protein aggregate. When
      the protein complex was treated with 4 M guanidinium hydrochloride and 0.1% SDS,
      11 monocomponent polypeptides could be detected by PAGE. Of these, four single
      polypeptides with molecular weights of 17,000-39,500 and isoelectric points of
      5.0-7.0 were observed to react with IgA separated from sera of children with
      celiac disease. The polypeptide molecules produced by fibroblasts in vitro bound
      to antireticulin and antiendomysium antibodies but not to antigliadin antibodies.
      The present observations show that tissue antibodies found to be specifically
      associated with celiac disease are generated against a synthesis product of
      fibroblasts, a cell-type known to synthesize a number of biologically active
      polypeptides. The fibroblast-derived extracellular matrix proteins and the formed
      autoantibodies may be important in the pathogenesis of gluten-sensitive
      enteropathy.

PMID- 8255671
TI  - Antibodies to human HSP60 in patients with juvenile chronic arthritis, diabetes
      mellitus, and cystic fibrosis.
AB  - The 60-kD heat shock protein (hsp60) has been implicated in the etiology and
      pathogenesis of both experimental and naturally occurring autoimmune diseases
      such as juvenile chronic arthritis (JCA). Human hsp60 is expressed in inflamed
      synovial tissue, and T lymphocytes both from peripheral blood and synovial fluid
      show reactivity to human hsp60. Because the anti-hsp60 B lymphocyte response has
      been less well studied, we have determined the occurrence of IgG anti-human hsp60
      antibodies in patients with JCA and various other autoimmune diseases of
      childhood. Serum IgG anti-human hsp60 antibodies in JCA patients were
      significantly higher compared with control children (358 and 163 U/mL,
      respectively). Within the group of JCA patients, the highest antibody titers were
      found in the subgroup with a polyarticular onset of JCA. IgG anti-human hsp60
      antibody levels in synovial fluid were 3- to 4-fold higher compared with paired
      serum samples. Because this difference was not found for total IgG or for
      irrelevant antibodies (anti-polyribosylribitol phosphate), this suggests local
      anti-hsp60 antibody production in the synovial compartment. The occurrence of
      anti-hsp60 antibodies is not specific for JCA but also is found in children with
      systemic lupus erythematosus and in cystic fibrosis, whereas mixed connective
      tissue disease and insulin-dependent diabetes are negative in this respect.
      Whether the anti-human hsp60 antibodies are directed toward species-specific
      sequences or to conserved sequences of the hsp60 molecule remains to be
      determined.

PMID- 8255672
TI  - Urinary oligosaccharide excretion in nephrotic syndrome.
AB  - Urinary oligosaccharides from nephrotic syndrome patients were investigated by
      Bio-Gel P-4 column chromatography and methylation analysis to clarify the
      electrostatic defects and size barrier defects in the glomerular basement
      membrane of nephrotic syndrome patients. The levels of urinary oligosaccharides
      (nmol/mg creatinine) in nephrotic syndrome patients were about 25 times the
      levels in controls. The ratio of neutral oligosaccharides to sialyl
      oligosaccharides was about 1:1 in the urine of nephrotic syndrome patients. The
      levels of neutral oligosaccharides in the urine of nephrotic syndrome patients
      were about 13 times that of controls. The proportion of trisialylated
      oligosaccharides in the urine of nephrotic syndrome patients was higher than that
      in galactosialidosis patients. These findings suggest that electrostatic defects
      and size barrier defects in the glomerular basement membrane might contribute to
      the characteristic oligosacchariduria of nephrotic syndrome patients. In
      addition, the structures of 11 different kinds of oligosaccharides that have not
      been previously reported were identified in the urine of nephrotic syndrome
      patients.

PMID- 8255673
TI  - Urinary insulin-like growth factor-II excretion in healthy infants and children
      with normal and abnormal growth.
AB  - The output of urinary IGF-II was measured by RIA in 12-h overnight urine samples
      obtained from 22 preterm and 15 full-term infants, 40 normal children, 18
      children with growth hormone (GH) deficiency, and 25 patients with idiopathic
      short stature. GH deficiency was defined as a peak to GH provocative tests < or =
      9.9 micrograms/L during two provocative tests. The authenticity of urinary IGF-II
      was confirmed by size exclusion chromatography. Statistical analysis was
      performed by one-way analysis of variance using the Student Neuman-Keuls test to
      detect intergroup differences at the level of p < 0.05. The preterm and full-term
      infants excreted significantly higher amounts of urinary IGF-II (18.4 +/- 1.7 and
      5.7 +/- 1.0 pmol/kg, respectively) compared with normal children (2.4 +/- 0.25
      pmol/kg; p < 0.001). The output of urinary IGF-II in preterm infants was greater
      than that observed in full-term infants (F = 84.7, p < 0.001). The control
      children excreted significantly more IGF-II (2.4 +/- 0.2 pmol/kg) than children
      with GH deficiency (0.9 +/- 0.1 pmol/kg) or idiopathic short stature (1.0 +/- 0.1
      pmol/kg; F = 13.5; p < 0.001). Analysis of urinary IGF-II excretion based on
      creatinine output yielded similar results. Data on urinary IGF-I and GH
      previously published were correlated and compared with the excretion pattern of
      urinary IGF-II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255674
TI  - Placental growth hormone levels in normal pregnancy and in pregnancies with
      intrauterine growth retardation.
AB  - To assess the possible role of placental growth hormone (GH) in fetoplacental
      growth, we measured placental and pituitary GH (GHN) in maternal plasma by means
      of two RIA using two MAb (5B4 recognizing both placental GH and GHN, and K24
      recognizing only GHN) during pregnancy. IGF-I also was measured by RIA in the
      same samples after extraction. A transverse study of 186 samples obtained between
      8 wk of amenorrhea (WA) and term confirmed the reported rise in GH
      immunoreactivity with 5B4 after 24 to 25 WA from 12.3 +/- 2.0 mU/L (mean +/- SEM)
      to a plateau of 27.5 +/- 3.4 mU/L at 34 to 35 WA together with the decrease in
      GHN to undetectable levels by 24 to 25 WA. IGF-I levels increased from 164.0 +/-
      44.6 micrograms/L at 24 to 25 WA to 331.6 +/- 63.6 micrograms/L at term. A
      longitudinal study of 31 normal pregnant women confirmed this hormonal pattern
      and the reported placental GH plateau after 35 WA. A drastic decrease in
      placental GH was observed with the onset of labor (from 26.9 +/- 2.1 to 2.7 +/-
      1.1 mU/L), whereas the decrease in IGF-I was not significant (from 212.9 +/- 26.5
      to 162.4 +/- 16.9 micrograms/L).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255675
TI  - Postnatal glucose kinetics in newborns of tightly controlled insulin-dependent
      diabetic mothers.
AB  - Infants of diabetic mothers are at risk of developing hypoglycemia postnatally.
      Strict control of blood glucose during pregnancy might result in adequate glucose
      homeostasis in the neonate. We followed 15 mother-infant pairs from the beginning
      of pregnancy until birth. Glucose kinetics in the infants were measured on the
      first day of life, using a stable isotope dilution technique. Furthermore, levels
      of alternative substrates, FFA, and ketone bodies were measured. All infants
      received i.v. glucose from birth onward at a rate of 3.4 +/- 0.7 mg/kg/min (mean
      +/- SD). There was no relationship between the parameters of control of the
      insulin-dependent diabetes mellitus in the mothers and glucose kinetics in their
      infants. Glucose turnover was 5.2 +/- 1.1 mg/kg/min, glucose production rate
      (GPR) was 1.8 +/- 1.1 mg/kg/min. GPR was significantly lower in the infants
      studied at the end of the first day of life (p < 0.01), irrespective of the
      glucose infusion rate. Furthermore, the lower GPR was associated with an
      increased concentration of ketone bodies, suggesting an increased production of
      ketone bodies in these infants. The relatively high GPR measured in the infants
      who were studied in the first hours postnatally may be the result of postnatal
      hormonal stimulation of glycogenolysis and/or gluconeogenesis. From this study,
      we conclude that glucose kinetics in infants of tightly controlled diabetic
      mothers appear to be normal. Interestingly, despite the near-optimal insulin
      therapy in the mothers, there is a relationship between the SD scores of birth
      weight and the mean 3rd-trimester blood glucose values.

PMID- 8255676
TI  - Estimation of total body fat and subcutaneous adipose tissue in full-term infants
      less than 3 months old.
AB  - Both fetal and neonatal nutrition may influence the body fat content of infants.
      Epidemiologic field studies would be facilitated by a simple method of measuring
      total body fat (TBF). The accuracy of a method, based on skinfold measurements,
      of estimating TBF was evaluated in 22 infants by comparing the results with those
      obtained by the body water dilution technique. Because the accuracy was poor, a
      modification was evaluated in 14 of the infants. The measurements were used to
      calculate the amounts of subcutaneous and nonsubcutaneous body fat. Estimates of
      the thickness of subcutaneous adipose tissue made with calipers and
      ultrasonography were compared with each other and with those obtained with Futrex
      5000, a device based on the principle of near-infrared interactance. The
      composition of the adipose tissue in biopsy specimen from 38 infants was analyzed
      and contained a mean of 0.66 g of fat/cm3. Results obtained by Futrex 5000
      correlated with subcutaneous adipose tissue thickness only when the latter was
      thin. Estimates of adipose tissue thickness by calipers were significantly higher
      than estimates by ultrasonography at the forearm, thigh, and calf, whereas the
      opposite was found at the triceps, biceps, umbilicus, and nipple. The amount of
      nonsubcutaneous fat, in relation to body weight minus subcutaneous fat, increased
      with age and was higher in girls than in boys. Skinfolds were poor predictors of
      TBF. However, it may be possible to predict TBF from anthropometric measurements
      if appropriate knowledge about the growth and development of adipose tissue in
      infancy are available.

PMID- 8255677
TI  - Pubertal changes in calcium kinetics in girls assessed using 42Ca.
AB  - The rate of calcium deposition in bone (Vo+) and the size of the exchangeable
      calcium pool in bone (EP) were measured in 50 girls aged 4.9 to 16.7 y using i.v.
      administered 42Ca. Both Vo+ and EP reached a maximum during early puberty and
      decreased in late puberty and more than 2 y postmenarche. In contrast, the
      initial mass of calcium distribution did not decrease in late puberty. The ratio
      of calcium deposition in bone to the exchangeable pool size, i.e. ko+ = Vo+/EP,
      was more closely correlated with length of time since menarche (r = 0.83, p <
      0.001) than with age (r = 0.65, p < 0.001), weight (r = 0.51, p < 0.001), or body
      mass index (r = 0.28, p = 0.05). The lower ko+ in late puberty indicates that as
      bone matures the fraction of the calcium pool that enters bone decreases.

PMID- 8255678
TI  - Relationship of carnitine and carnitine precursors lysine, epsilon-N
      trimethyllysine, and gamma-butyrobetaine in drug-induced carnitine depletion.
AB  - Plasma concentrations and rates of urinary excretion of carnitine and some of its
      precursors were studied in three groups of children receiving drugs known to
      cause carnitine depletion. Patients in group A received pivampicillin and a molar
      equivalent of carnitine for 7 d. Patients in group B received pivampicillin with
      a 5.8-fold molar excess of carnitine for 1 wk. Patients in group C were treated
      chronically with valproic acid and received a molar equivalent (to valproic acid)
      of carnitine for 14 d. Patients in group A had markedly increased (16-fold)
      urinary carnitine ester excretion concomitant with diminished urinary free
      carnitine and gamma-butyrobetaine output and lower plasma free carnitine
      concentration. Supplementation with one molar equivalent of carnitine (to
      pivampicillin) was ineffective in preventing the reduction of plasma carnitine
      concentration observed with pivampicillin treatment alone. For group B patients,
      administration of excess carnitine resulted in a further increase (35-fold) of
      urinary carnitine ester output with no decrease of plasma carnitine
      concentration, urinary gamma-butyrobetaine, or free carnitine excretion. For
      patients in group C, the initially low plasma free and total carnitine
      concentrations and urinary output of carnitine and carnitine esters markedly
      increased with carnitine supplementation, but urinary excretion of gamma
      butyrobetaine remained unchanged. The plasma concentrations and urinary output of
      L-lysine and epsilon-N-trimethyllysine remained unchanged within each group
      before and after treatment. A positive linear correlation was found between
      urinary epsilon-N-trimethyllysine and 3-methylhistidine output, indicating that
      the rate of epsilon-N-trimethyllysine excretion correlates with the amount of 3
      methylhistidine liberated by protein turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255679
TI  - Control of the cardiac consequences of myocardial ischemia and reperfusion by L
      propionylcarnitine: age-response and dose-response studies in the rat heart.
AB  - We assessed the protective effects of L-propionylcarnitine, a liposoluble
      analogue of carnitine, in the isolated heart from rats of different ages
      subjected to global ischemia and reperfusion. Hearts from neonatal (3- to 7-d
      old), immature (2- to 3-wk-old), and adult rats were retrogradely perfused with a
      modified Krebs bicarbonate buffer and subjected to ischemia and reperfusion. L
      Pro-pionylcarnitine was given either before ischemia and throughout reperfusion
      (protocol 1) or during reperfusion only (protocol 2). Coronary flow, heart rate,
      left ventricular developed pressure, and left ventricular end-diastolic pressure
      were measured throughout the perfusion period. Ventricular arrhythmias and
      creatine kinase leakage were measured at the time of reperfusion. Postischemic
      recovery of coronary flow and left ventricular developed pressure were age
      dependent and were not affected by L-propionylcarnitine, but recovery of heart
      rate was decreased in neonatal and immature hearts by 10(-4) M and 10(-5) M (p <
      0.05), compared with controls (protocol 2). L-Propionylcarnitine always reduced
      creatine kinase leakage in the adult (p < 0.05) compared with controls (protocol
      1). No effects on creatine kinase leakage were observed in neonatal and immature
      hearts. This study found that injury induced by ischemia and reperfusion was age
      dependent. Neonatal and immature hearts were more resistant to injury than adult
      hearts. The recovery of cardiac function was not affected by L
      propionylcarnitine. However, in the adult rat hearts, L-propionylcarnitine given
      before ischemia and throughout reperfusion was protective by reducing creatine
      kinase leakage.

PMID- 8255680
TI  - Left ventricular oxygen and substrate uptake in chronically hypoxemic lambs.
AB  - Myocardial oxygen demand may be increased in chronically hypoxemic lambs because
      of their increased heart rate. Therefore, we determined whether left ventricular
      (LV) oxygen supply, oxygen uptake and oxygen demand were proportionally increased
      in 6-wk-old lambs, after 4 wk of hypoxemia (n = 15), as compared with control
      lambs (n = 14). In addition, we determined whether LV glucose, pyruvate, lactate,
      FFA and ketoacids uptake were altered in hypoxemic lambs, because of alterations
      in arterial glucose, pyruvate and lactate concentrations, that may occur in
      hypoxemia. Hypoxemia was induced by the combination of an atrial septal defect
      and pulmonary stenosis. Arterial oxygen saturation was decreased in hypoxemic
      lambs (67 +/- 8 versus 91 +/- 3%, p < 0.001), Hb concentration was increased, so
      that arterial oxygen concentration was similar in both groups of lambs.
      Myocardial mass (61 +/- 13 versus 44 +/- 9 g, p < 0.001) and total myocardial
      blood flow (117 +/- 36 versus 62 +/- 27 mL.min-1, p < 0.001) were increased,
      mainly due to right ventricular hypertrophy. LV oxygen demand, estimated by the
      rate pressure product (2072 +/- 465 versus 1467 +/- 358 kPa.beat.min-1, p <
      0.001), and oxygen uptake (723 +/- 223 versus 556 +/- 184 mumol.min-1 x 100 g-1,
      p < 0.05) were proportionally increased in hypoxemic lambs. LV oxygen supply
      increased linearly with oxygen uptake (r = 0.96) in all lambs, by adjustments in
      LV blood flow, which was increased in hypoxemic lambs (168 +/- 41 versus 134 +/-
      45 mL.min-1 x 100g-1, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255681
TI  - Specific approach on dose-response curves to inhaled carbachol assessed by the
      interruption technique in children.
AB  - To determine significant thresholds obtained by bronchial challenge tests in
      children for assessment of bronchial reactivity, changes of respiratory
      resistance (Rint) induced by inhaled carbachol were evaluated in 20 asthmatic
      children (10 boys and 10 girls, mean age 9.1 +/- 2.8 y, range 5 to 15 y) and 20
      healthy control children (10 boys and 10 girls, mean age 12.1 +/- 2.6 y, range 8
      to 16 y). Baseline lung function was assessed by whole body plethysmography. The
      carbachol challenge test was performed by the interruption technique. The
      objectives were to search for the most predictable provocation dose (PD)
      according to statistical and practical considerations. The statistical argument
      is given by the condition that the target PD must definitively be out of the
      measurement error of baseline values. From the practical point of view, the
      object is to provoke the subjects the least amount possible. As thresholds of
      bronchial reactivity, the provocation doses inducing a 50%, 65%, 75%, or 100%
      increase in baseline Rint (PD50, PD65, PD75, PD100) were computed by a 4th power
      polynomial function analysis including data points of the entire dose-response
      curve. In comparison, a new threshold, the "variance based" provocation dose
      (PDvb), was defined as threshold to be definitively above the range of the
      baseline Rint variation before initiating challenge [PDvb > mean + 2 SD range of
      Rint(0)]. Although the PD50, PD65, PD75, and PD100 can be adequately computed by
      the 4th power function from the whole dose-response curve, comparison between the
      different provocation thresholds revealed that PDvb gives the best values to
      differentiate between healthy and asthmatic children (p < 0.002).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8255682
TI  - Maturation of the ventilatory response to CO2 in the newborn piglet.
AB  - In 12 piglets aged 0 to 1.5 d, we assessed the contribution of the peripheral and
      central chemoreceptors in mediating the ventilatory response to CO2 and the
      apneic threshold during normoxia (arterial O2 tension, 13 kPa) using the dynamic
      end-tidal forcing technique. With this technique, the ventilatory response is
      separated into a peripheral and a central component using a two-compartment
      model. Each component is described by a CO2 sensitivity, a time constant, a
      transport delay time, and an apneic threshold. The means of the estimated
      parameters per piglet were compared with those obtained in a previous study in
      piglets aged 2 to 11 d (Wolsink JG, Berkenbosch A, DeGoede J, Olievier CN: J
      Physiol (Lond) 456:39-48, 1992). The ratio of the peripheral CO2 sensitivity to
      the total CO2 sensitivity was found to be significantly lower in the younger
      group of piglets (0.14 +/- 0.10 versus 0.29 +/- 0.10), whereas the apneic
      threshold was significantly higher (2.52 +/- 1.12 kPa versus 1.06 +/- 1.46 kPa).
      We conclude that the peripheral chemoreceptors are responsive to CO2 shortly
      after birth. However, the ventilatory response to CO2 maturates in the first few
      days after birth by an increase in the relative contribution of the peripheral
      chemoreceptors to the total ventilatory response and a decreasing apneic
      threshold.

PMID- 8255683
TI  - Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged
      rabbits are influenced by the instillation technique.
AB  - Surfactant bolus instillation has been reported to cause changes in arterial
      blood pressure (BP) and cerebral blood flow velocities which may increase the
      risk of intraventricular haemorrhage. To avoid these effects, slow tracheal
      infusion was evaluated as a possible alternative method of surfactant
      administration. Saline lung lavages were performed in 13 anesthetized and
      artificially ventilated adult rabbits to produce respiratory distress syndrome.
      Curosurf (CS, 200 mg/kg) labeled with 14C-dipalmitoyl-phosphatidylcholine (-DPPC)
      and/or red microspheres (RMS) was instilled into the trachea either as a single
      bolus (n = 8) or by infusion during 45 min via a side-channel within the wall of
      the tracheal tube (n = 5). An arterial cannula was placed for monitoring of blood
      gases and BP. To determine surfactant distribution, the lungs were cut into 60-70
      pieces and radioactivity and/or the number of RMS were measured in each piece.
      The distribution of RMS was closely related to the distribution of 14C-DPPC (r =
      0.96). Bolus instillation of CS led to a prompt and sustained increase in PaO2
      (from < 10.5 to > 40 kPa within 2 min), a transient decrease in BP, and a
      reasonably homogeneous pulmonary surfactant distribution. Tracheal infusion of CS
      changed neither BP nor PaO2 during the observation period of 60 min. The
      pulmonary distribution of CS was extremely uneven after infusion. The
      distribution of exogenous surfactant and its effects on gas exchange are
      influenced by the instillation method. An inadequate instillation technique may
      add to the causes of "poor response" after surfactant replacement.

PMID- 8255684
TI  - The physiologic effects of surfactant treatment on gas exchange in newborn
      premature infants with hyaline membrane disease.
AB  - To describe the physiologic effects of surfactant treatment on gas exchange in
      human premature infants with hyaline membrane disease, functional residual
      capacity (FRC), tidal volume (VT), the alveolar portion of tidal volume (VA),
      alveolar ventilation (VA), nitrogen clearance index, effective breath fraction
      calculated as VA/VT, compliance of the respiratory system, and arterial oxygen
      and carbon dioxide tensions were measured in 17 patients before and 0.5, 2, and 6
      h after the administration of a single dose of either a synthetic surfactant
      (SS), Exosurf (n = 10), or a bovine surfactant (BS), Survanta (n = 7). By 2 h,
      treatment with either BS or SS was followed by an increase in the
      arterial/alveolar ratio of PO2 (a/A) and in FRC (p < 0.01 for both a/A and FRC).
      The a/A and FRC improved sooner (p < 0.001) and to a greater extent (p < 0.01)
      after BS than after SS. Compliance of the respiratory system and VT were
      decreased after either BS or SS at 0.5 h (p < 0.01) and remained decreased after
      SS at 2 h (p < 0.01). There was no significant change in VA or VA after either BS
      or SS. Because FRC and a/A increased without an accompanying increase in VA, VA,
      or compliance of the respiratory system, we believe that the immediate increase
      in FRC in this study was caused by stabilization of gas exchange units already
      being ventilated in addition to recruitment of new units.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8255685
TI  - Expression of immunoreactive cytidine 5'-triphosphate: cholinephosphate
      cytidylyltransferase in developing rat lung.
AB  - The principle rate-limiting enzyme required for phosphatidylcholine production is
      cytidine 5'-triphosphate:cholinephosphate cytidylyltransferase. Two functional
      forms of cytosolic cytidylyltransferase have been previously identified: an
      active high-molecular weight multimer (H-form) and a relatively inactive low
      molecular-weight species (L-form). In the present study, we examined the
      maturational changes in enzyme mass in the subcellular fractions of fetal,
      neonatal, and adult rat lungs. Total enzyme mass, measured by immunoblotting of
      total cellular lung homogenates, revealed a large amount of immunoreactive enzyme
      during the fetal and neonatal periods and relatively low levels of enzyme in the
      adult lung. A similar developmental profile for enzyme mass was noted in the
      cytosolic and microsomal fractions. Further, in the fetus, the majority of
      cytosolic enzyme mass was expressed as an inactive form (L-form). Stimulation of
      fetal cytosol with phosphatidylglycerol converted the enzyme mass from an
      inactive form (L-form) to an active form (H-form). In the adult, a substantial
      portion of the cytosolic enzyme mass was expressed as the active species (H
      form). These observations suggest that cytidylyltransferase activity early in
      lung development is accompanied by an increase in enzyme mass, the majority of
      which exists as an inactive low-molecular-weight species. In contrast, high
      levels of enzyme activity are maintained in the adult lung, despite relatively
      low levels of enzyme mass, because a significantly greater portion of the enzyme
      mass is expressed as an active high-molecular-weight multimer.

PMID- 8255686
TI  - A noninvasive transcutaneous alternative to rectal thermometry for continuous
      measurement of core temperature in the piglet.
AB  - Deep body temperature is an important and accepted index of health status in
      newborn infants. There are no easily used accurate methods for continuous deep
      body temperature measurements. Oral and tympanic membrane temperatures correlate
      well with rectal temperature but are not easily adapted to continuous
      measurement. We devised a noninvasive transcutaneous temperature sensor for
      continuous deep body temperature measurement that relies on the principle that,
      under steady state conditions, the temperature at the thermally insulated surface
      of a warm body, i.e. a zero heat loss surface, will be in equilibrium with the
      warmest part of the body. We used a standard clinical temperature probe placed
      between the skin and the mattress and attached to the skin with a foam adhesive
      disk. We used standard skin temperature probe attachment disks, which are also
      designed to provide thermal insulation to the skin temperature probe. We tested
      the hypothesis that this transcutaneous temperature would track body temperature
      as indicated by rectal temperature. In six anesthetized (pentobarbital) newborn
      piglets (1600 +/- 200 g) placed on their abdomen in a convectively warmed infant
      incubator, we measured continuously the following temperatures for 5 h:
      transcutaneous over lower and upper abdomen, brown fat, rectal, and descending
      aorta. To examine the influence of environment, we varied the incubator air
      temperature between 32 degrees and 36 degrees C. Both transcutaneous temperatures
      tracked the rectal temperature, within 0.2 degree C for transcutaneous over lower
      abdomen and within 0.3 degree C for transcutaneous over upper abdomen.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8255687
TI  - Apnea and rapid eye movement sleep excess in the piglet during recovery from
      hyperthermia.
AB  - This investigation tested the hypothesis that artificially induced mild
      hyperthermia and recovery from hyperthermia in the developing newborn piglet (2
      10 d of age) alter sleep state patterns and respiratory control. Continuous
      measurements of sleep state, respiratory pattern, carbon dioxide production and
      oxygen consumption were made before, during, and after a 3-h period of sustained
      hyperthermia. During hyperthermia, rectal temperatures were raised a mild 1-1.5
      degree C above normal, well below the levels likely to cause severe physiologic
      distress in this species. This resulted in a disruption of the sleep state
      pattern characterized by a decrease in duration of rapid eye movement (REM)
      episodes, whereas immediately afterwards, during recovery, the amount of REM
      sleep increased. In some cases the amount of REM sleep in recovery more than
      doubled the basal level. Apneas were rarely observed during hyperthermia, but in
      recovery there was an increase in the total amount of time spent in apnea in both
      REM and non-rapid eye movement sleep states with a predominance in the REM state.
      Arousal responses to chemostimulation were not affected at this time. We conclude
      that the sleeping newborn piglet does indeed show marked changes in sleep state
      pattern (particularly REM sleep) and in the amount of apnea recorded during and
      immediately after only a mild increase in core temperature.

PMID- 8255688
TI  - Influence of mild hypothermia on hypoxic-ischemic brain damage in the immature
      rat.
AB  - Recent studies in adult animals have shown that even small decreases in brain or
      core temperature ameliorate the damage resulting from hypoxic-ischemic insults.
      To determine the effect of minor reductions in ambient temperature either during
      or after an hypoxic-ischemic insult on the brain of the immature rat, 7-d
      postnatal rat pups underwent unilateral common carotid artery ligation followed
      by exposure to hypoxia in 8% oxygen for 3 h. Control animals were maintained at
      37 degrees C during hypoxia-ischemia. Intraischemic hypothermia was induced
      during the insult at temperatures of 34 degrees C and 31 degrees C. Postischemic
      hypothermia was induced by exposing rat pups that underwent hypoxia at 37 degrees
      C to recovering environments of 34 degrees C and 31 degrees C. Temperatures were
      recorded every 15 min from thermistor probes placed in the ipsilateral hemisphere
      and rectally. Neuropathologic alterations were assessed at 30 postnatal d. During
      hypoxia, animals became poikilothermic. Brain damage occurred in 90% of rat pups
      exposed to hypoxia-ischemia at 37 degrees C. Cerebral injury significantly
      decreased with decreasing temperatures during hypoxia-ischemia (p < 0.01). Only
      30% of rats had brain damage when exposed to hypoxia-ischemia at 34 degrees C,
      and none of the rats exposed at 31 degrees C had brain damage. In contrast, there
      was no difference in the extent of cerebral injury between rat pups recovered
      under hypothermic conditions of either 34 degrees C or 31 degrees C compared with
      those recovered at 37 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255690
TI  - Fahraeus and Fahreaus-Lindqvist effects for neonatal and adult red blood cell
      suspensions.
AB  - In blood vessels with diameters less than 500 microns, both the hematocrit and
      viscosity decrease with decreasing tube diameter [Fahraeus effect (FE) and
      Fahraeus-Lindqvist effect (FLE)]. Because both effects may be influenced by red
      blood cell (RBC) volume and osmolality, the effects of RBC type and suspending
      medium osmolality (216, 294, and 473 mosmol/kg) on tube hematocrit (HT) and
      relative viscosity (eta r) in narrow tubes (32 to 145 microns diameter) were
      studied for 0.40 L/L (40%) hematocrit suspensions of human neonatal and adult RBC
      in buffer. Osmolality of 473 mosmol/kg caused shrinkage of RBC by 20% so that
      neonatal RBC assume the volume of adult RBC in isotonic buffer. The FLE and FE
      were present for both neonatal and adult RBC suspensions regardless of
      osmolality. The viscosity reduction when going from a 145- to a 32-microns tube
      was greatest for the hypertonic neonatal and adult RBC: changes were -44% (473
      mosmol/kg) and -31% (294 mosmol/kg) for neonatal RBC, and -39% (473 mosmol/kg), 
      34% (294 mosmol/kg), and -21% (216 mosmol/kg) for adult RBC. The eta r were
      significantly lower (7% on average) for isotonic neonatal RBC compared with adult
      cells in 32-microns (p < 0.025), 46-microns, and 146-microns tubes (p < 0.001).
      In contrast, HT and thus the FE were less affected by RBC type or osmolality
      (only 13% change over entire range of osmolality and diameter): relative HT
      values were systematically lower (p < 0.02), and the FE greater, for isotonic
      neonatal versus adult RBC.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255689
TI  - Polyethylene glycol-conjugated superoxide dismutase improves recovery of
      postischemic hypercapnic cerebral blood flow in piglets.
AB  - We tested the hypothesis that administering polyethylene glycol-conjugated
      superoxide dismutase (PEG-SOD) either before global cerebral ischemia or at the
      time of reperfusion would alter recovery of cerebral blood flow (CBF;
      microspheres) response to alteration in arterial PCO2 in pentobarbital
      anesthetized, mechanically ventilated piglets (1 to 2-wk old). CBF was measured
      at an arterial PCO2 of approximately 3.3, 5.3, and 8.7 kPa before and 2 h after
      ischemia (10 min aortic cross clamp). To determine the effect of preischemic
      versus postischemic treatment with PEG-SOD, each piglet received two i.v. drug
      injections of either 30,000 U PEG-SOD or an equal volume of PEG diluent in a
      randomized, blinded fashion before ischemia and just before reperfusion. Cerebral
      oxygen consumption and somatosensory evoked potentials were measured during
      reperfusion as an assessment of brain function. During reperfusion, no group
      demonstrated delayed hypoperfusion. Hypercapnic CBF was less during reperfusion
      (48 +/- 6 mL/min/100 g) compared with preischemia (69 +/- 10 mL/min/100 g) in
      PEG/PEG-treated piglets. However, hypercapnic CBF during reperfusion was not
      different from preischemic values with either preischemic or postischemic PEG-SOD
      treatment. Improved return of hypercapnic CBF in PEG-SOD-treated piglets was not
      attributable to improved postischemic cerebral oxygen consumption. Somatosensory
      evoked potential amplitude was decreased similarly during reperfusion
      (approximately 25% of preischemic values) in all groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8255691
TI  - Decreased superoxide anion and hydrogen peroxide production by neutrophils and
      monocytes in human immunodeficiency virus-infected children and adults.
AB  - The higher susceptibility to serious bacterial infections of patients,
      particularly children, infected with the human immunodeficiency virus (HIV) may
      be due in part to defective function of their phagocytic cells. We examined the
      ability of polymorphonuclear cells and monocytes of HIV-infected children and
      adults to generate superoxide anion (SO) and hydrogen peroxide (HP) and compared
      it with that of cells from normal children and adults. SO was measured by
      reduction of cytochrome c and HP by horseradish peroxidase-dependent oxidation of
      phenol red. The cells were incubated in 96-well plates at 37 degrees C for 2 h
      before the assay and the nonadherent cells then removed. Readings for SO were
      taken at 10, 30, 60, and 120 min after stimulation with phorbol myristate
      acetate; HP production was assayed after 90 min. The SO and HP production by
      polymorphonuclear cells and monocytes from both HIV-infected children and adults
      was consistently found to be markedly lower than that of cells from age-matched
      controls. The magnitude of the difference in response between patients and
      control cells also increased with increasing incubation time. Thus, phagocytic
      cells from HIV-infected children and adults are defective in their ability to
      generate reactive oxygen intermediates, and this defect may make them more
      vulnerable to bacterial and fungal infections.

PMID- 8255693
TI  - Acceptance of the Howland Award: childhood nutrition--50 years later.

PMID- 8255692
TI  - Howland Award presentation to Lewis A. Barness.

PMID- 8255694
TI  - Smart bombs and dumb scientists?

PMID- 8255695
TI  - Visual alchemy: stereoscopic adaptation produces kinetic depth from random noise.
AB  - Observers perceive incoherent motion and no hint of depth when viewing stochastic
      motion, in which stimulus elements move in all possible directions. As earlier
      work has shown, depth can be specified by introducing a brief interocular delay
      between the presentation of corresponding animation frames of this 'noise' to the
      left and right eyes. A study is reported in which observers were adapted to a
      stereoscopic display consisting of coherent planes of motion at different depths.
      This stereoscopic adaptation caused incoherent depthless motion to take on the
      qualities of structure and depth, and it could nullify the depth induced by
      interocular delay. The findings are interpreted within the context of a neural
      model consisting of units selectively responsive to different directions of
      motion at different planes of depth.

PMID- 8255696
TI  - Head movement changes apparent depth order in a motion-parallax display.
AB  - The hypothesis that the apparent visual depth is determined by the proximal
      velocity relative to the position of the head was examined in three experiments.
      Apparent protrusion/recession changed when subjects observed a moving random-dot
      pattern with their heads tilted sideways or rotated in the horizontal plane. This
      is ascribed to lateral head movement, which increases the proximal velocity when
      the dots and the subjects' heads are moving in opposite directions, and decreases
      the proximal velocity when both are moving in the same direction. Changes in the
      direction of movement of the stimulus caused a reversal of the apparent
      protrusion/recession. The resultant proximal velocity of the stimulus determined
      the order of depth of surfaces when the movement of the stimulus was linked to
      the subject's head movement.

PMID- 8255697
TI  - Four questions of time to contact: a critical examination of research on
      interceptive timing.
AB  - Four questions concerning the use and perception of time to contact, tc, are
      identified. (i) Is tc information used in the timing of interceptive actions?
      (ii) If so, what control strategies are used? (iii) What are the perceptual
      sources of tc information and which of them do people use? (iv) How is the
      information extracted by the perceptual systems? Research relevant to these
      questions is reviewed and analysed. In connection with question (i), theoretical
      work on the special case of catching a moving object is analysed. It is concluded
      that treatments of catching which involve the use of tc information provide the
      best account of timing. In connection with question (ii), two types of control
      strategy suggested in the literature are identified: an intermittent strategy and
      a continuous strategy. Evidence for a continuous strategy is reconsidered and
      shown to be at least as well if not better accounted for by an intermittent
      strategy. Other empirical evidence for intermittent control is also discussed. In
      connection with question (iii) a simple unifying method is outlined with which
      all tc information so far presented in the literature can be derived, and
      examples are given. The viability of various types of information as sources of
      tc is examined by considering the errors which would result from their use.
      Finally, in connection with question (iv) the role of 'looming detectors' in the
      extraction of tc information is considered. These are frequently proposed as
      mechanisms for extracting the tc information provided by Lee's optic variable,
      tau. The analysis provided indicates that, despite the existence of a well-known
      and popular theory, due mainly to Lee, about how interceptive actions are timed,
      very little is actually known about perceptual timing. It is not yet certain
      whether tc information is used in interceptive timing tasks, what kinds of
      control strategies are involved, what sources of information people use to time
      their actions, or what perceptual processing is involved in the extraction of tc
      information.

PMID- 8255698
TI  - Selective attention and temporal-order judgment.
AB  - A procedure originally introduced by Sternberg and coworkers was used to examine
      the effect of selective attention on temporal-order judgment. Two-response and
      three-response paradigms were employed. As in Sternberg et al's work, a shift of
      psychometric functions for the two-response paradigm was found that suggested
      shorter latency for the stimulus to which attention was directed. However, no
      shift was noted for the three-response paradigm. This discrepancy can be
      explained by the assumption that the shift obtained for the two-response paradigm
      results from an artifact caused by a specific task. The artifact occurs because
      the instruction to attend to a particular stimulus induces a response bias when
      the subject is forced to guess in situations where he/she cannot recognize the
      temporal order of stimuli. The artifact disappears with the three-response
      paradigm where the subject has the additional option to respond "simultaneous".

PMID- 8255699
TI  - New depth to the Muller-Lyer illusion.
AB  - It is demonstrated that when the two halves of the Muller-Lyer illusion are shown
      separately to the two eyes this can result in a perception of the binocularly
      viewed shaft as slanted in depth. For short fin lengths, the magnitude of this
      slant can be predicted by the extent of the ordinary two-dimensional illusion.
      This result is discussed in relation to Julesz's claim that stereoscopic matching
      of the images in the two eyes must precede whatever process is responsible for
      the Muller-Lyer illusion (whereas the reported illusion seems to imply the
      reverse). The cyclopean Muller-Lyer demonstration on which Julesz's argument is
      based is reexamined. It is suggested that the matching of coarse-scale features
      in the images in the two eyes may help to explain both the cyclopean and the
      reported three-dimensional Muller-Lyer illusion.

PMID- 8255700
TI  - Obliquity integration: variations on a theme of Delboeuf.
AB  - An optical-geometrical illusion, described by Delboeuf and not familiar to
      specialists, is investigated. The results of two experiments show that the
      divergence between a bar filled with parallel slanting lines and a line drawn
      above it is clearly related to this angle of the lines which fill the bar. The
      illusion is already present when this angle is 10 degrees, reaches its maximum at
      20 degrees, decreases at 30 degrees, and almost disappears at 40 degrees. These
      results are similar to those found for the tilt illusion, are slightly different
      from those found for the rod-and-frame illusion, and differ greatly from those
      found for the Zollner illusion. The other variables considered-the distance
      between the slanting lines filling up the bar, the distance between the upper
      line and the bar, and the width of the bar--do not influence the illusion as
      much. Since either the line appears as diverging from the bar, or the bar seems
      inclined in relation to the line, the illusion should be considered a complex
      one. The small oblique lines inside the bar induce obliquity in the opposite
      sense in the display, but which of the elements is seen as diverging from the
      other depends on which of the two is established as the frame of reference.

PMID- 8255701
TI  - Amodal completion in mouse vision.
AB  - The question of whether phenomena of human perception such as amodal completion
      are also present in visual perception in the mouse was investigated. Three
      experiments based on a simultaneous-discrimination task were carried out with the
      aid of a jumping-stand similar to the one used by Lashley. The subjects were 36
      male mice (DBA/J); 12 took part in each experiment. After reaching the learning
      criterion (87% correct responses), the mice performed 15 test trials which were
      interpolated between the learning trials. The test trials were constructed so as
      to allow the observation of any perceptual phenomena similar to amodal
      perception. Of the 36 subjects, 23 reached the criterion necessary to access the
      test phase. A significant number of them (17 out of 23, chi 2 = 5.261, p = 0.021)
      adopted a decisional strategy that seemed to indicate the occurrence of phenomena
      similar to amodal completion, and a trend in the same direction was observed in
      the performance of the other 6 subjects. The results allow the conclusion that a
      perceptual phenomenon which is similar to amodal completion in humans is present
      even at this phylogenetic level. Alternative interpretations are discussed.

PMID- 8255702
TI  - Constraints on haptic integration of spatially shared object dimensions.
AB  - A study of the haptic integration of texture, shape, and hardness of nonplanar
      solid objects is reported. In experiment 1 the relative discriminability of the
      objects along each dimension was assessed. While levels of texture and shape were
      equally discriminable, hardness discriminations proved considerably more
      difficult. The extent of dimensional integration in a speeded classification task
      when both dimensions could be extracted from the same local patch was
      investigated in experiments 2 and 3. In experiment 2 subjects were initially
      encouraged to attend to a nontargeted dimension covarying with a targeted one.
      The nontargeted dimension was subsequently held constant (withdrawn). In
      experiment 3 dimensional variation was introduced which was uncorrelated with the
      targeted property during the course of categorization and hence discouraged
      subjects from attending to the nontargeted property. The results of these two
      studies converged in showing evidence of bidirectional dimensional integration
      between texture and shape and unidirectional integration when hardness was the
      targeted dimension. The failure to integrate hardness into categorization based
      on texture or shape was attributed to the difficulty of hardness discriminations.
      Integration effects in experiment 3 were not consistently smaller than those in
      experiment 2, which suggests a strong involuntary component to dimensional
      integration. The results of an analysis of the accompanying hand movements are
      interpreted in terms of constraints on dimensional integration. Implications for
      visual, cross-modal, and two-handed codimensional processing are also discussed.

PMID- 8255703
TI  - The possible pain experienced during execution by different methods.
AB  - The physiology and pathology of different methods of capital punishment are
      described. Information about this physiology and pathology can be derived from
      observations on the condemned persons, postmortem examinations, physiological
      studies on animals undergoing similar procedures, and the literature on emergency
      medicine. It is difficult to know how much pain the person being executed feels
      or for how long, because many of the signs of pain are obscured by the procedure
      or by physical restraints, but one can identify those steps which are likely to
      be painful. The general view has been that most of the methods used are virtually
      painless, and lead to rapid dignified death. Evidence is presented which shows
      that, with the possible exception of intravenous injection, this view is almost
      certainly wrong.

PMID- 8255704
TI  - Similarity between concurrent visual discriminations: dimensions and objects.
AB  - Accuracy is often reduced when two visual discriminations must be made
      concurrently ("divided attention"). According to a hypothesis originally proposed
      by Treisman (1969) and Allport (1971), this result should depend on the
      similarity of required discriminations. When discriminations concern different
      visual dimensions, they should be made in somewhat separate visual subsystems,
      reducing interference between them. This prediction was tested in two
      experiments, involving discriminations of shape, size, orientation, and spatial
      frequency. In different conditions of divided attention, concurrent
      discriminations concerned either the same or different dimensions, and either one
      or two objects. The results showed that performance depends only on the number of
      relevant objects, not on the number or similarity of required discriminations.
      They suggest that selective attention to an object is a coordinated state in
      which the outputs of multiple visual subsystems are made concurrently available
      for control of behavior.

PMID- 8255705
TI  - Evidence for the persistence of visual guidance information.
AB  - An earlier study from our laboratory provided initial support for the hypothesis
      that information facilitating visual guidance persists in the absence of retinal
      stimulation. The present study supports and extends this hypothesis with three
      experiments in which visually occluded subjects positioned a point of light at
      the location of a previously viewed target and also walked in the direction of a
      previously viewed path. In both tasks, performance was possible following
      occlusion, and in all cases, performance slowly and significantly decreased with
      longer durations of occlusion. This decay in performance was gradual and had a
      "half-life" of greater than 15 sec. Absolute performance was correlated across
      tasks. The effect of occlusion on absolute error in the localization performance
      was relatively stable within individuals over a 3-week period. The biological
      utility of guidance information persistence is discussed along with implications
      for space constancy, illusions of motion, and problems of disorientation.

PMID- 8255706
TI  - Analyzing coefficients of psychophysical power functions.
AB  - Some mathematical properties of coefficients of power functions were analyzed.
      The size of correlations between intercepts (the logarithm of the coefficient)
      and exponents depends on the choice of unit of measurement of the physical
      stimuli. When the mean of logarithms of a set of responses is uncorrelated with
      the exponent, the absolute size of the correlation between the intercept and the
      exponent increases as the geometric mean of the stimulus measures deviates from
      one. When the geometric mean is less than one, the correlation is positive, and
      when it is greater than one, the correlation is negative. Similar trends hold for
      a nonzero correlation between the exponent and the mean logarithm of a set of
      responses. The power of statistical tests of differences between mean intercepts
      also depends on the geometric mean of the stimuli. Power is reduced as the
      geometric mean deviates from one. Effects are illustrated with real data.

PMID- 8255707
TI  - Lightness, brightness, and brightness contrast: 1. Illuminance variation.
AB  - Changes of annulus luminance in traditional disk-and-annulus patterns are
      perceptually ambiguous; they could be either reflectance or illuminance changes.
      In more complicated patterns, apparent reflectances are less ambiguous, letting
      us place test and standard patches on surrounds perceived to be different grays.
      Our subjects matched the apparent amounts of light coming from the patches
      (brightnesses), their apparent reflectances (lightnesses), or the brightness
      differences between the patches and their surrounds (brightness contrasts). The
      three criteria produced quantitatively different results. Brightness contrasts
      matched when the patch/surround luminance ratio of the test was approximately
      equal to that of the standard. Lightness matches were illumination invariant but
      were not exact reflectance matches; the different surrounds of test and standard
      produced a small illumination-invariant error. This constant error was negligible
      for increments, but, for decrements, it was approximately 1.5 Munsell value
      steps. Brightness matches covaried substantially with illuminance.

PMID- 8255708
TI  - Lightness, brightness, and brightness contrast: 2. Reflectance variation.
AB  - Changes of annulus luminance in traditional disk-and-annulus patterns can be
      perceived to be either reflectance or illuminance changes. In the present
      experiments, we examined the effect of varying annulus reflectance. In Experiment
      1, we placed test and standard patch-and-surround patterns in identical Mondrian
      patchworks. Only the luminance of the test surround changed from trial to trial,
      appearing as reflectance variation under constant illumination. Lightness matches
      were identical to brightness matches, as expected. In Experiment 2, we used only
      the patch and surround (no Mondrian). Instructions said that the illumination
      would change from trial to trial. Lightness and brightness-contrast data were
      identical; illumination gradients were indistinguishable from reflectance
      gradients. In Experiment 3, the patterns were the same, but the instructions said
      that the shade of gray of the test surround would change from trial to trial.
      Lightness matches were identical to brightness matches, again confirming the
      ambiguity of disk-and-annulus patterns.

PMID- 8255709
TI  - Mesopic lightness, brightness, and brightness contrast.
AB  - At mesopic mean luminances, a fixed luminance contrast produces less brightness
      contrast than it does at photopic luminances. This suggests that lightnesses of
      surfaces might also be altered at low luminances. I measured lightness,
      brightness, and brightness contrast in CRT simulations of achromatic paper
      patchworks. The illuminance of the standard pattern was fixed, producing 0.12,
      1.2, or 12 cd/m2. The illuminance on the test pattern was varied in a lightness
      constancy paradigm. Constant brightness contrast required more luminance contrast
      at lower mean luminances. Failures of lightness constancy occurred at the lowest
      mean luminances, but they were minor in comparison with the loss of brightness
      contrast in the same pattern. These results have implications for imaging
      applications. Often, image content falls in both the photopic and the mesopic
      ranges. Our results indicate that brightness contrast may decrease substantially
      in low-luminance regions without large changes of surface lightness.

PMID- 8255710
TI  - Context effects in judging taste intensity: a comparison of variable line and
      category rating methods.
AB  - The effect of stimulus range and stimulus spacing was examined when subjects
      registered the perceived intensity of sweet liquids using either a matching
      procedure (Experiment 1) or category rating (Experiment 2). The matching
      procedure is conceptually similar to absolute magnitude estimation, whereby
      subjects match their impression of number size to their impression of the
      subjective magnitude of a stimulus. In Experiment 1, subjects matched their
      impression of the stimulus to their impression of the magnitude of the length of
      a continuously variable line under their control. In Experiment 2, subjects rated
      perceived sweetness on a vertical 13-point scale with five equally spaced verbal
      labels. In both experiments, three sets of four sucrose concentrations were
      employed. In two of these sets, a set of weaker solutions and a set of stronger
      solutions, concentrations were separated by 0.25 log units. In a third set, which
      spanned the range of concentrations used in the other two sets (0.87 to 27.36%
      w/v), solutions were separated by 0.5 log units. An examination of both
      individual and group data showed the matching procedure to be less susceptible to
      a range bias than the rating procedure. In particular, a single intensity
      function accommodated data from individual ranges better when the matching
      procedure was used than when the rating procedure was used. No effect of stimulus
      spacing was evident in the data from either procedure.

PMID- 8255711
TI  - Perceiving the size of trees: biological form and the horizon ratio.
AB  - Physical constraints produce variations in the shapes of biological objects that
      correspond to their sizes. Bingham (in press-b) showed that two properties of
      tree form could be used to evaluate the height of trees. Observers judged
      simulated tree silhouettes of constant image size appearing on a ground texture
      gradient with a horizon. According to the horizon ratio hypothesis, the horizon
      can be used to judge object size because it intersects the image of an object at
      eye height. The present study was an investigation of whether the locus of the
      horizon might account for Bingham's previous results. Tree images were projected
      to a simulated eye height that was twice that used previously. Judgments were not
      halved, as predicted by the horizon ratio hypothesis. Next, the original results
      were replicated in viewing conditions that encouraged the use of the horizon
      ratio by including correct eye height, gaze level, and visual angles. The heights
      of cylinders were inaccurately judged when they appeared with horizon but without
      trees. Judgments were much more accurate when the cylinders also appeared in the
      context of trees.

PMID- 8255712
TI  - The frame turns also: factors in differential rotation in pictures.
AB  - When pictures of simple shapes (square, diamond) were seen frontally and
      obliquely, (1) the shapes with a deeper extent into pictured space underwent more
      rotation (Goldstein, 1979), which is an apparent turning to keep an orientation
      toward an observer's changing position; (2) there was little effect of whether
      the observer knew the picture surface's orientation in real space, except that
      such knowledge could prevent multistability; and (3) depicted picture frames also
      rotated. In other experiments, figural and frame rotations were independent of
      each other, and rotation was shown for real frames. The rotation of depthless
      depictions suggests that at least two rotational factors exist, one that involves
      the object's virtual depth and one that does not. The nature of this second
      factor is discussed. Frame rotation appeared to subtract from object rotation
      when the two were being compared; this could explain a paradox in picture
      perception: Depicted orientations often seem little changed over viewpoints,
      despite (apparent) rotations with respect to real-space coordinates.

PMID- 8255713
TI  - Distractor clustering enhances detection speed and accuracy during selective
      listening.
AB  - The effects of distractor clustering on target detection were examined in two
      experiments in which subjects attended to binaural tone bursts of one frequency
      while ignoring distracting tones of two competing frequencies. The subjects
      pressed a button in response to occasional target tones of longer duration
      (Experiment 1) or increased loudness (Experiment 2). In evenly spaced conditions,
      attended and distractor frequencies differed by 6 and 12 semitones, respectively
      (e.g., 2096-Hz targets vs. 1482- and 1048-Hz distractors). In clustered
      conditions, distractor frequencies were grouped; attended tones differed from the
      distractors by 6 and 7 semitones, respectively (e.g., 2096-Hz targets vs. 1482-
      and 1400-Hz distractors). The tones were presented in randomized sequences at
      fixed or random stimulus onset asynchronies (SOAs). In both experiments,
      clustering of the unattended frequencies improved the detectability of targets
      and speeded target reaction times. Similar effects were found at fixed and
      variable SOAs. Results from the analysis of stimulus sequence suggest that
      clustering improved performance primarily by reducing the interference caused by
      distractors that immediately preceded the target.

PMID- 8255714
TI  - The McCollough effect: dissociating retinal from spatial coordinates.
AB  - Three experiments were conducted to dissociate the perceived orientation of a
      stimulus from its orientation on the retina while inducing the McCollough effect.
      In the first experiment, the typical contingency between color and retinal
      orientation was eliminated by having subjects tilt their head 90 degrees for half
      of the induction trials while the stimuli remained the same. The only relation
      remaining was that between color and the perceived or spatial orientation, which
      led to only a small contingent aftereffect. In contrast, when the spatial
      contingency was eliminated in the second experiment, the aftereffect was as large
      as when both contingencies were present. Finally, a third experiment determined
      that part of the small spatial effect obtained in the first experiment could be
      traced to hidden higher order retinal contingencies. The study suggested that
      even under optimal conditions the McCollough effect is not concerned with real
      world properties of objects or events. Implications for several classes of
      theories are discussed.

PMID- 8255715
TI  - The Muller-Lyer contrast illusion: a computational approach.
AB  - When a temporal delay is interposed between the contextual elements (wings) and
      the focal element (central axis) of the Muller-Lyer figures, the usual
      assimilation illusion changes to an illusion of contrast; that is, judged axis
      length is contrasted away from rather than assimilated toward the context
      provided by parallel extents between wings. Presentation time for the preceding
      contextual wings on the order of 1 sec or more was needed to produce contrast
      effects in judgments of the following focal axis (Experiment 3) and, given
      sufficient presentation time, these contrast effects were largely unaffected by
      the length of the temporal delay between contextual and focal elements, appearing
      equally strong for delays between 0 and 2 sec (Experiments 1 and 2). These
      results are consistent with a representational basis for these contrast effects
      that is high-level and long-lived. The Muller-Lyer contrast illusion may reflect
      the inadvertent error arising from basing judgments about particular objects on
      information about attribute differences among objects. Such judgmental errors may
      be the natural consequence of constrained computations that make explicit
      information required for certain common tasks, but at the expense of obscuring
      information required for less common tasks.

PMID- 8255716
TI  - Providing a sensory basis for models of visual information acquisition.
AB  - Our major goal is to account for some simple digit-recall data with a theory that
      integrates two models from two scientific traditions. The random-sampling model,
      founded in the memory and attention literature, holds that (1) stimulus features
      are randomly sampled throughout the course of stimulus presence and (2)
      proportion correct recall is equal to the ratio of sampled features to total
      features. The linear-filter model, founded in the vision and sensation
      literature, holds that the initial stages of the visual system act as a low-pass
      temporal filter on the input stimulus, resulting in a time-varying sensory
      response in the nervous system. We report two experiments in which a variable
      duration, masked, four-digit string had to be immediately recalled. Experiment 1
      was designed principally to replicate past data confirming the basic random
      sampling model. Like others, we were able to confirm the model only by endowing
      it with an additional processing-delay assumption: that feature sampling does not
      begin until the stimulus has been physically present for some minimal duration.
      Experiment 2 was an extension of Experiment 1 in which the target stimulus was
      preceded, 250 msec prior to its onset, by a 50-msec pre-presentation of the same
      stimulus called a prime. The Experiment 2 results allowed the following
      conclusions. First, the initial processing delay found in Experiment 1 is
      immutably tied to stimulus onset; that is, if there are two stimulus onsets,
      separated even briefly in time, there are two associated processing delays.
      Second, processing rate is essentially unaffected by the prime's presentation.
      Third, being presented with a 50-msec prime is equivalent, in terms of memory
      performance, to increasing unprimed stimulus duration by approximately 30 msec;
      the prime can thus said to be worth 30 msec of additional exposure duration. This
      third conclusion seems superficially paradoxical, in the sense that one would
      expect that having seen a 50-msec prime would be equivalent to increasing
      exposure duration by at least the same 50 msec. However, both the initial
      processing delays and the 30-msec prime's worth are natural consequences of our
      theory that conjoins the random-sampling model with the linear-filter model.

PMID- 8255717
TI  - The range effect as a function of stimulus set, presence of a standard, and
      modulus.
AB  - The intramodal range effect (an inverse relationship between stimulus range and
      exponent in Stevens's power law) has been well documented, but its conditions
      have not been tested. Both the estimates of stimulus magnitudes and their
      exponents are affected by context, stimulus location, and different standards and
      moduli, but how these variables might interact with the variable of stimulus
      range has not been studied. In the present research, exponents were derived from
      magnitude estimates of line length for each of three different stimulus ranges at
      two different locations on the scale of length, with or without a modulus. Moduli
      of 50 and 500 permitted an analysis of the effect of response magnitude on the
      range effect. Because different ranges had stimulus values in common, the effect
      of range and location on exponents from those common values could be determined.
      Exponents decreased as stimulus range increased, but only in the free-modulus
      condition. For that condition, exponents derived from magnitude estimates of only
      the common stimuli also showed the range effect and response magnitude did not
      influence the range effect. Exponents were higher for stimulus ranges at the
      lower location, but location does not appear to contribute to the range effect.
      Although the range effect is not explained, the conditions under which it holds
      and some factors that may influence it are considered.

PMID- 8255718
TI  - Exercise training fails to prevent glucocorticoid-induced muscle alterations in
      young growing rats.
AB  - The aim of this study was to determine the impact of chronic treatment for 8
      weeks with hydrocortisone acetate (5 mg kg-1 day-1) on skeletal muscles, and to
      evaluate whether sprint training can prevent glucocorticoid-induced muscle
      atrophy better than endurance training. Biochemical, histological and contractile
      properties were employed to determine the influence of this steroid on skeletal
      musculature, and the results were compared to pair-weight animals to take into
      account the influence of corticoids on growth rate. It was found that
      hydrocortisone acetate treatment results in a stunted growth, adrenal atrophy and
      depressed plasma corticosterone levels. Mild corticoid-induced losses of muscle
      mass and protein content (9%-13%) were observed in fast-twitch skeletal muscles.
      It appeared that the impact of corticoids is strictly directed toward type IIb
      fibres, which displayed a 12%-18% reduction in cross-sectional areas. No
      alterations occurred in plantaris contractile speed or tensions properties.
      Neither endurance training (30 m/min; 90 min/day; 5 days/week) nor sprint
      training (60 m/min; 15 min/day; 5 days/week) for 8 weeks was able to counteract
      the effects of corticoids. These data suggest that increased contractile
      activity, as induced by treadmill running, is not sufficient to counteract the
      muscular effects of glucocorticoids when administered at a dose of 5 mg kg-1 day
      1.

PMID- 8255719
TI  - Identification of PTH-responsive Na/H-exchanger isoforms in a rabbit proximal
      tubule cell line (RKPC-2).
AB  - Renal epithelial cells may express apical and basolateral Na/H exchangers which
      are different in their physiological regulation and different in their
      sensitivities to the inhibitor amiloride. In the present study RKPC-2 cells [a
      Simian virus 40 (SV-40) transformed cell line of rabbit S2 proximal tubular
      origin] were examined for localization (apical vs basolateral) and regulation of
      Na/H-exchange activity(ies) by parathyroid hormone (PTH). In addition, using
      specific cDNA probes we determined the expression of multiple isoforms of Na/H
      exchangers in RKPC-2 cells. By the use of BCECF [2',7',bis(2-carboxyethyl)-5,6
      carboxyfluorescein intracellular pH (pHi) indicator] and single cell fluorescence
      microscopy, Na/H-exchange activities (defined as initial rate of Na-dependent pHi
      recovery) were found on the apical and basolateral membrane of RKPC-2 cells;
      apical and basolateral transport activities differed in sensitivity to
      dimethylamiloride, the basolateral being more sensitive. Northern blot analysis
      demonstrated the presence of a 5.2-kb transcript, related to Na/H-exchanger
      activity NHE-1, and a 3.2-kb transcript, related to Na/H-exchanger activity NHE
      2. PTH (10(-8) M) inhibited apically and basolaterally located Na/H-exchanger
      activities. The inhibitory effect of PTH was mimicked by 8-bromo-adenosine 3'5'
      cyclic monophosphate (cAMP); it was blunted in the presence of H-89 (inhibitor of
      protein kinase A) and was unaffected by calphostin C (inhibitor of protein kinase
      C). In contrast to 8-bromo-cAMP (and PTH), exposure of RKPC-2 cells to phorbol 12
      myristate 13-acetate (TPA) caused a significant stimulation of both Na/H-exchange
      activities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255720
TI  - Intracellular ATP modulates desensitization of acetylcholine receptors
      controlling chloride current in Lymnaea neurons.
AB  - Chloride current activated by nicotinic acetylcholine receptors (AChR) was
      examined in dialysed voltage-clamp neurons of Lymnaea stagnalis. Fast superfusion
      of acetylcholine (ACh) evoked an inward current rapidly rising to a peak followed
      by a decline due to desensitization. When adenosine triphosphate with Mg2+
      (MgATP, 2-10 mM) was added intracellularly the peak of the ACh-induced current
      was increased and its decay was slowed down. ATP without Mg2+ did not affect
      desensitization. Mg2+ alone accelerated desensitization. Intracellular treatment
      with an inhibitor of ATP synthesis, sodium arsenate, increased the
      desensitization rate and decreased the peak current. MgATP after arsenate wash
      out restored the initial characteristics of the response; a mixture of glycolytic
      substrates had a similar effect. A non-hydrolysable analogue of ATP, adenosine
      [gamma-thio]triphosphate mimicked ATP action after arsenate removal but was
      weaker; another non-hydrolysable analogue, adenylyl imidodiphosphate, did not
      affect desensitization at all. Intracellular treatment of the neurons with
      alkaline phosphatase accelerated current decay. The data suggest that a change in
      intracellular ATP concentration modulates AChR desensitization via an enzymatic
      process that might be phosphorylation of AChR or some associated protein(s).
      Involvement of Ca2+ homeostasis cannot be excluded. The results are compared with
      the data obtained on vertebrate tissues under conditions promoting
      phosphorylation.

PMID- 8255721
TI  - Rapid stimulation of Na+/H+ exchange by 1,25-dihydroxyvitamin D3; interaction
      with parathyroid-hormone-dependent inhibition.
AB  - We have examined the rapid effect of 1,25-dihydroxyvitamin-D3 [1,25(OH)2D3] on
      apical Na+/H+ exchange activity in opossum kidney (OK) cells and in MCT cells (a
      culture of simian-virus-40-immortalized mouse cortical tubule cells) grown on
      filter support. Addition of 1,25(OH)2D3 (10 nM) for 1 min increased apical Na+/H+
      exchange activity [recovery from an acid load; measured by 2',7'-bis(2
      carboxyethyl)-5(6)-carboxyfluorescein] in OK cells (by 56%) and in MCT cells (by
      36%). The cellular mechanisms involved in 1,25(OH)2D3-dependent stimulation of
      Na+/H+ exchange were analysed in OK cells; stimulation of Na+/H+ exchange by
      1,25(OH)2D3 was not prevented by actinomycin D. Applying parathyroid hormone
      (PTH) reduced Na+/H+ exchange activity in OK cells (by 34% at 10 nM, 5 min);
      1,25(OH)2D3 "reversed" PTH-induced inhibition, either when PTH was added prior to
      1,25(OH)2D3 or when the two agonists were applied together. 1,25(OH)2D3 had no
      effect on basal OK cell cAMP content or on [Ca2+]i (fura-2). 1,25(OH)2D3
      attenuated PTH-induced cAMP accumulation and had no effect on the PTH-dependent
      increase in [Ca2+]i. These data suggest a regulatory control (stimulation) of
      proximal tubular brush-border Na+/H+ exchange by 1,25(OH)2D3. This effect is non
      genomic and might in part be explained by a release from cAMP-dependent control
      of transport activity.

PMID- 8255722
TI  - Valine oxidation in the rat medullary thick ascending limb.
AB  - In the kidney, a branched-chain amino acid transferase (BCAAT) activity has been
      localized mainly in the medullary thick ascending limb (MTAL) of the rat nephron.
      BCAAT is the first enzyme involved in the metabolic pathway of the three branched
      chain amino acids (BCAA): leucine, isoleucine and valine. The present work has
      been designed to study valine catabolism. Valine and leucine oxidation in MTAL
      were compared by measuring the rate of 14CO2 produced when these substrates were
      incubated as sole substrates at a final concentration of 1 mM. Since glucose is
      also metabolized in MTAL, valine and leucine oxidation were quantified also in
      the presence of glucose (1 mM). The results show that: (1) valine oxidation was
      greater than that of leucine (63.0 +/- 4.7 vs 39.7 +/- 5.2 pmol.h-1 x micrograms
      1 protein, respectively; P < 0.001). As previously shown, leucine oxidation was
      found to be increased in the presence of glucose whereas glucose oxidation
      decreased. In contrast, the presence of glucose strongly diminished valine
      oxidation (19.2 +/- 1.9 vs 63.1 +/- 4.7 pmol.h-1 x micrograms-1 protein; P <
      0.001) whereas glucose oxidation was increased in the presence of valine (268.2
      +/- 14.9 vs 229.6 +/- 16.2 pmol.h-1 x micrograms-1 protein; P < 0.05). We
      conclude that in rat MTAL, under near physiological conditions (in the presence
      of glucose, as in vivo), leucine is a preferential respiratory fuel as compared
      to valine. However, valine supports energetic salt transport and facilitates
      glucose oxidation.

PMID- 8255723
TI  - Furosemide stimulates renin expression in the kidneys of salt-supplemented rats.
AB  - This study was conducted to obtain information about a possible influence of salt
      transport by the thick ascending limb of Henle (TALH) and the macula densa on the
      expression of renin in the kidney. To this end, adult male rats were
      subcutaneously infused with furosemide (12 mg/24 h), an established inhibitor of
      TALH and macula densa salt transport, or with vehicle for 6 days. The animals had
      free access to chow, water and salt water (0.8% NaCl, 0.1% KCl) to maintain salt
      and water balance. Chronic furosemide treatment led to a 20-fold increase in
      urine flow rates and 50% increase in kidney weights, while urine osmolality
      decreased by 60% and body weight gain decreased by 40% in the furosemide-treated
      animals. Plasma renin activities increased from 2.9 +/- 0.5 ng angiotensin I h-1
      ml-1 in controls to 10.6 +/- 2.2 ng angiotensin I h-1 ml-1 in furosemide-treated
      rats. In parallel, kidney areas immunoreactive for renin increased by 80% and the
      renal content of renin mRNA increased by 120% in the animals receiving
      furosemide. Under the assumption that the effects seen on renal renin expression
      were primarily due to the inhibition of TALH and macula densa function by
      furosemide, our findings suggest that salt transport across the TALH and macula
      densa exerts a negative control function not only on the secretion but also on
      the expression of renin in the kidney.

PMID- 8255724
TI  - Adenosine reduces the potassium conductance of guinea pig submucosal plexus
      neurons by activating protein kinase A.
AB  - Intracellular recordings were made from S neurons of the submucosal plexus
      isolated from the guinea pig ileum. Adenosine or its analog 2-chloroadenosine
      (CADO) depolarized about 80% of neurons; previous work has shown that this
      results from activation of an A2 receptor. The depolarization was associated with
      an increase in membrane input resistance, became smaller with membrane
      hyperpolarization, reversed polarity at the potassium equilibrium potential and
      was mimicked and occluded by calcium-free solutions or by cadmium, suggesting
      that it is due to a reduction in a calcium-dependent potassium conductance. Both
      forskolin (though not 1,9-dideoxyforskolin) and phorbol 12,13-dibutyrate (PDBu)
      mimicked and occluded the action of CADO. Staurosporine (a nonspecific inhibitor
      of protein kinases) blocked the depolarization induced by the phorbol ester
      within 5 min, and blocked the effects of forskolin and CADO in 15-35 min. The
      depolarization caused by CADO was inhibited by the specific inhibitor of protein
      kinase A KT5720 [(8R*,9S*,11S*)-(-)-9-hydroxy-9-n-hexylester-8-methyl-2,3,9,10
      tet rahydro-8,11-epoxy-1H,8H,11H-2,7b,11a-triazadibenzo[a,g]c ycloocta[cd e]-trin
      den-1-one], whereas this inhibitor did not affect the depolarization induced by
      PDBu. The results are consistent with the control of this potassium conductance
      by protein kinase C, protein kinase A and intracellular calcium, and they
      indicate that adenosine reduces the conductance by activating protein kinase A.

PMID- 8255726
TI  - Evidence for agonist-induced export of intracellular Ca2+ in epithelial cells.
AB  - There is increasing evidence that some agonists not only induce intracellular
      Ca2+ increases, due to store release and transmembranous influx, but also that
      they stimulate Ca2+ efflux. We have investigated the agonist-stimulated response
      on the intracellular Ca2+ activity ([Ca2+]i) in the presence of thapsigargin (10(
      8) mol/l, TG) in HT29 and CFPAC-1 cells. For CFPAC-1 the agonists ATP (10(-7)-10(
      3) mol/l, n = 9), carbachol (10(-6)-10(-3) mol/l, n = 5) and neurotensin (10(-10)
      10(-7) mol/l, n = 6) all induced a concentration-dependent decrease in [Ca2+]i in
      the presence of TG. Similar results were obtained with HT29 cells. This decrease
      of [Ca2+]i could be caused by a reduced Ca2+ influx, either due to a reduced
      driving force for Ca2+ in the presence of depolarizing agonists or due to agonist
      regulated decrease in Ca2+ permeability. Using the fura-2 Mn2+ quenching
      technique we demonstrated that ATP did not slow the TG-induced Mn2+ quench. This
      indicates that the agonist-induced [Ca2+]i decrease in the presence of TG was not
      due to a reduced influx of Ca2+ into the cell, but rather due to stimulation of
      Ca2+ export. We used the cell attached nystatin patch clamp technique in CFPAC-1
      cells to examine whether, in the presence of TG, the above agonists still led to
      the previously described electrical changes. The cells had a mean membrane
      voltage of -49 +/- 3.6 mV (n = 9). Within the first 3 min ATP was still able to
      induce a depolarization which could be attributed to an increase in Cl-
      conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255725
TI  - Comparison of acid/base status in conscious and anaesthetized rats during acute
      hypothermia.
AB  - Acute hypothermia was surface-induced in unrestrained conscious rats at two
      different levels, moderate (30 degrees C TB) and severe (20 degrees C TB). Data
      reflecting the acid/base status were determined. The values obtained for moderate
      hypothermia were compared with the acid/base pattern observed during hypothermia
      induced by two different anaesthetics, sodium pentobarbital and urethane, at room
      temperature. Conscious, hypothermic animals developed an apparent respiratory
      alkalosis, with an increase in pHa (from 7.476 to 7.546 in moderate hypothermia
      and from 7.484 to 7.563 in severe hypothermia) correlated with a decrease in
      arterial bicarbonate levels (from 22.9 to 16.8 mmol l-1 and from 20.7 to 14.9
      mmol l-1 respectively). Lactate increased slightly in conscious, severely
      hypothermic rats (1.02 mmol l-1). This acid/base pattern was clearly different
      from that seen in sodium pentobarbital (mild respiratory acidosis) and urethane
      induced hypothermia (metabolic acidosis). These results suggest that conscious
      rats follow a pattern closer to that underlying the relative alkalinity shown by
      many poikilotherms than to that underlying the constant pH shown in hibernating
      mammals. This latter pattern, nevertheless, approaches that observed during
      moderate pentobarbital hypothermia and the acid/base pattern during shallow
      hypothermia in birds. Anaesthesia may interfere with the development of the
      processes that lead to the acid/base pattern observed in conscious animals.

PMID- 8255727
TI  - Oscillations of receptor-operated cationic current and internal calcium in single
      guinea-pig ileal smooth muscle cells.
AB  - In single cells isolated from guinea-pig ileal smooth muscle, held under voltage
      clamp at -40 mV or -50 mV by patch pipette in the whole-cell recording mode,
      carbachol (CCh) evoked an oscillatory inward cationic current. The frequency of
      current oscillations increased with increasing CCh concentration. CCh-evoked
      current oscillations were followed very closely by oscillations in intracellular
      free Ca2+ estimated from the Indo-1 signal, and were abolished by inclusion of
      EGTA in the pipette solution. Ryanodine and heparin, but not nifedipine, blocked
      the generation of current oscillations. CCh-evoked current oscillations were
      abolished upon withdrawal of extracellular calcium and restored upon its
      reintroduction. Inclusion of GTP[gamma S] in the pipette solution caused the
      generation of an oscillatory inward current, which was blocked by ryanodine. The
      present results are consistent with the hypothesis that CCh-evoked cationic
      current is gated by activation of a G protein and is steeply dependent on
      [Ca2+]i, fluctuations in the release of Ca2+ from stores during carbachol's
      action produce oscillations in [Ca2+]i which cause similar oscillations in the
      cationic current.

PMID- 8255728
TI  - Is there a Na+/Ca2+ exchanger in macrophages and in lymphocytes?
AB  - In two blood cell types, peritoneal murine macrophages and Jurkat cells (a human
      T cell line), we have examined whether a Na+/Ca2+ exchange was present and what
      could be its functional importance. In non-stimulated macrophages, the
      intracellular Ca2+ concentration, [Ca2+]i, was unchanged when Li+ was substituted
      for external Na+. However, after stimulation by platelet-activating factor (PAF),
      the Ca2+ response was larger when the extracellular solution contained Li+ rather
      than Na+ ions. In stimulated macrophages, the rate of Ca2+ extrusion was smaller
      in a Li(+)- than in a Na(+)-containing medium. The net electrochemical gradient
      for ionic movements through the Na+/Ca2+ exchanger, during the course of the
      response of macrophages to PAF, was determined by combining the measurements of
      membrane potential (in patch-clamp), of [Ca2+]i (with fura-2), and of the
      intracellular Na+ concentration (with sodium-binding benzofuran isophthalate).
      These results show that macrophages possess a Na+/Ca2+ exchange that only
      functions as a Ca2+ extruder, and this only when [Ca2+]i has been increased, for
      instance following PAF stimulation. In T lymphocytes, before or after stimulation
      by an anti-CD3 antibody, no Na+/Ca2+ activity could be detected by measuring
      either [Ca2+]i, or the rate of Ca2+ extrusion. Even if a Na+/Ca2+ exchanger was
      present in these cells, its equilibrium potential would be such that it would not
      allow Ca2+ influx but only Ca2+ extrusion.

PMID- 8255729
TI  - Small and intermediate conductance chloride channels in HT29 cells.
AB  - Recently, it has been shown that intermediate conductance outwardly rectifying
      chloride channels (ICOR) are blocked by cytosolic inhibitor (C. I.) found in the
      cytosol of human placenta and epithelial cells. C. I. also reduced the baseline
      current in excised membrane patches of HT29 cells. In the present study, this
      effect of C. I. was characterized further. Heat treated human placental cytosol
      was extracted in organic solvents and dissolved in different electrolyte
      solutions. It is shown that the reduction of baseline conductance (g(o)) is
      caused by inhibition of small non-resolvable channels, which are impermeable to
      Na+ and SO4(2-), but permeable to Cl-. The regulation of these small Cl(-)
      conducting channels (g(o)) and of ICOR was examined further. First, no activating
      effects of protein kinase A (PKA) on the open probability (Po) of the ICOR or on
      the g(o)) were observed. The Po of the ICOR was reduced by 22% in a Ca(2+)-free
      solution. g(o) was insensitive to changes in the Ca2+ activity. The effects of C.
      I. from a cystic fibrosis (CF) placenta and the CF pancreatic duct cell line
      CFPAC-1 were compared with the effects of corresponding control cytosols, and no
      significant differences between CF and control cytosols were found. We conclude
      that the excised patches of HT29 cells contain ICOR and small non-resolvable Cl(
      )-conducting channels which are similarly inhibited by C. I.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8255730
TI  - The pathway for refilling intracellular Ca2+ stores passes through the cytosol in
      human leukaemia cells.
AB  - The pathway for refilling the intracellular Ca2+ stores of HL60 and U937 human
      leukaemia cells loaded with fura-2 has been investigated. On addition of external
      Ca2+ to cells with empty stores there was an increase in the cytosolic Ca2+
      concentration ([Ca2+]i) which preceded the refilling of the stores. The increase
      in [Ca2+]i was faster than the refilling, by 3- to 15-fold, depending on the cell
      type. In measurements in single HL60 cells we found that the refilling of the
      stores correlated with the extent of the [Ca2+]i increase on addition of external
      Ca2+. The cells showing no [Ca2+]i increase were unable to refill their stores.
      The addition of Ni2+ to the extracellular medium prevented both the [Ca2+]i
      increase and the refilling of the stores. These results indicate that the
      limiting step for store refilling is the entry of Ca2+ from the extracellular
      medium to the cytosol. Hence, we conclude that extracellular Ca2+ cannot gain
      access directly to the intracellular Ca2+ stores in these cells, but must first
      enter the cytosol and be taken up from there into the stores.

PMID- 8255731
TI  - Force-velocity relation and isomyosins in soleus muscles from two strains of mice
      (C57 and NMRI).
AB  - We compared soleus muscles from two strains of mice, NMRI and C57. Soleus muscles
      from NMRI mice produced slower twitches and lower maximum tetanic force (Fo) but
      higher maximum tetanic stress (So), (owing to their smaller weight). Their Hill's
      velocity constant (b) was lower, but their force constant (a/So), their maximum
      velocity of unloaded shortening (Vu) and their maximal mechanical power (Pmax)
      were similar. All soleus muscles contained two isomyosins (SM2 and IM) and the
      two myosin heavy chains (MHC1 and MHC2A) corresponding to type I fibres and type
      IIA fibres; however, soleus muscles from NMRI strain had higher proportions of
      isomyosin SM2 and of myosin heavy chain 2A. Regression equations were computed
      between the mechanical variables and the myosin heavy chain content. Using a
      simple hypothesis, the results were used to estimate the mechanical properties of
      type I and type IIA fibres. We conclude that type IIA fibres from soleus muscle
      are mechanically more similar to slow-twitch type I fibres than to fast-twitch
      type II fibres. The results also suggest a hypothesis to account for the
      diversity of isomyosins, by a matching diversity of mechanical properties based
      on a separate physiological control of the three factors that control Pmax.

PMID- 8255732
TI  - Peripheral blood flows during colorectal distension in anaesthetised dogs.
AB  - Distension of the descending colon elicits reflex cardiovascular responses,
      including increases in heart rate and arterial blood pressure. To study the
      relative contribution of vasoconstriction in individual vascular beds to this
      reflex response, experiments were performed on seven dogs anaesthetised with
      chloralose and instrumented with electromagnetic flowmeters around the superior
      mesenteric, the left renal and the left external iliac arteries. The colorectal
      portion of the intestine was distended at constant pressure (36.6 mm Hg, 4.9 kPa
      mean; range 25-50 mm Hg, 3.3-6.7 kPa) with warm Ringer solution for periods of 2
      min. After a set of control distensions, the experiments were performed whilst
      the reflex rise in arterial pressure was prevented by removal of blood from the
      arterial tree. In control distensions arterial pressure increased by 11.3 +/- 1.5
      mm Hg, 1.51 +/- 0.12 kPa (mean +/- SEM). In distensions at constant arterial
      pressure, peripheral blood flows were altered to different extents in the three
      territories studied: vascular resistance increased by 30.8 +/- 5.6% (P < 0.01) in
      the mesenteric, by 4.1 +/- 1.5% (P < 0.03) in the renal, and by 15.2 +/- 6.8%
      (NS) in the external iliac bed. We conclude that colorectal distension may
      reflect activation of a function-specific pathway of the sympathetic nervous
      system, which leads to much greater vasoconstriction in the splanchnic
      circulation than in renal or musculocutaneous circulations.

PMID- 8255733
TI  - Muscle fiber types of women after resistance training--quantitative
      ultrastructure and enzyme activity.
AB  - Muscle biopsies of the vastus lateralis muscle taken before and after 18 weeks of
      resistance training were compared by preparing frozen cross sections for electron
      microscopy and using adjacent sections for fiber typing by myosin ATPase
      activity. Quantitative ultrastructural changes were observed in histochemically
      identified muscle fiber types of twelve young women who underwent the training.
      The percentage of type IIB fibers decreased and IIA fibers increased. The cross
      sectional area of all major fiber types increased with training. The absolute
      volume of myofibrils, intermyofibrillar space, and mitochondria increased with
      training for most major fiber types (type I, IIA and IIAB), but the relative
      volume percentages were not significantly changed because of corresponding fiber
      hypertrophy. Mean mitochondrial size for types I and IIA and myofibril size for
      types IIC and IIB increased significantly with training. The capillary number per
      fiber and density did not change with training. Activity levels were measured for
      selected glycolytic and oxidative enzymes. Cytochrome oxidase and hexokinase
      increased significantly with training, while creatine kinase, citrate synthase,
      phosphofructokinase, glyceraldehyde phosphate dehydrogenase and hydroxyacyl CoA
      dehydrogenase enzymes were not significantly altered. The results suggest that
      this type of high-repetition resistance training causes the intracellular
      components of all fiber types to increase proportionally with an increase in
      fiber size. In addition, the enzyme analysis indicates the muscle as a whole may
      increase its oxidative phosphorylation capacity in conjunction with the decreased
      percentage of type IIB fibers.

PMID- 8255734
TI  - Adenosine and adenine nucleotides are independently released from both the nerve
      terminals and the muscle fibres upon electrical stimulation of the innervated
      skeletal muscle of the frog.
AB  - The independent release of adenosine and adenine nucleotides upon electrical
      stimulation was studied in the innervated sartorius muscle of the frog after
      blockade of the extracellular catabolism of adenosine monophosphate (AMP) through
      exo-AMP deaminase and ecto-5'-nucleotidase. Nerve stimulation (30 min, 0.2Hz)
      induced the release of both adenosine (19 +/- 3 pmol) and adenine nucleotides
      (101 +/- 7 pmol). Experiments performed in the presence of tubocurarine (5
      microM) to prevent purine release due to nerve-evoked muscle twitching, or under
      direct stimulation of the muscle in low calcium solutions to prevent pre-synaptic
      release of purines, showed that there was an evoked release of adenosine and
      adenine nucleotides both from the nerve endings and from the twitching muscle
      fibres. Removal of ecto-5'-nucleotidase inhibition shows that the catabolism of
      adenine nucleotides released during stimulation contributes in about 50% to the
      amount of endogenous extracellular adenosine. When only one of the enzymes
      catabolizing AMP (ecto-5'-nucleotidase or exo-AMP deaminase) was inhibited, the
      evoked release of adenine nucleotides was undetectable, suggesting that each
      enzyme is able to catabolize all the AMP formed from adenine nucleotides released
      upon stimulation. It is concluded that the concentration of endogenous
      extracellular adenosine is under the control of the relative activities of exo
      AMP deaminase and ecto-5'-nucleotidase.

PMID- 8255735
TI  - Criteria for perforated-patch recordings: ion currents versus dye permeation in
      human T lymphocytes.
AB  - Nystatin-perforated patches are now frequently used to help preserve cytoplasmic
      integrity during patch-clamp recordings. We used voltage-dependent K+ currents in
      human T lymphocytes to compare conventional whole-cell recordings with perforated
      patch recordings (PPR). Although there were pronounced differences in the
      inactivation kinetics, we discovered that our PPR recordings were not "intact".
      In every case, coinciding with the gradual capacitance transient increase and
      decrease in access resistance, we observed that large (> MW 800) fluorescent dyes
      enter the cell from the pipette. These results suggest that caution is required
      when using differences in the properties of the currents to confirm that the
      nystatin-containing patch is intact.

PMID- 8255736
TI  - Bell-shaped activation of inositol-1,4,5-trisphosphate-induced Ca2+ release by
      thimerosal in permeabilized A7r5 smooth-muscle cells.
AB  - There is no consensus about the different types of Ca2+ transport processes in
      the endoplasmic reticulum that are targeted by the sulphydryl reagent thimerosal.
      We have therefore investigated how thimerosal affects the various Ca2+ transport
      processes in permeabilized A7r5 smooth-muscle cells, using an unidirectional
      45Ca2+ flux technique. Thimerosal up to a concentration of 32 microM did not have
      an effect on the passive 45Ca2+ leak from the stores, while higher concentrations
      increased this aspecific leak. Thimerosal inhibited the endoplasmic reticulum
      Ca2+ pump with an EC50 of 9 microM. Thimerosal exerted a biphasic effect on the
      Ca2+ release induced by inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] with a
      stimulation of the release at thimerosal concentrations below 10 microM, and an
      inhibitory effect at higher concentrations. Thimerosal (2.5-250 microM) did not
      exert an effect on the specific binding of [3H]Ins(1,4,5)P3 to its receptor,
      indicating that it probably did not act at the level of the binding site. This
      finding contrasts with the effect of the closely related sulphydryl reagent
      parachloromercuriphenylsulphonate, which, at high concentrations, inhibited
      [3H]Ins(1,4,5)P3 binding. The effects of thimerosal were largely prevented by the
      sulphydryl reducing agent dithiothreitol (3 mM). We conclude that thimerosal
      concentrations ranging from 0.32 to 1 microM can stimulate the Ins(1,4,5)P3
      induced Ca2+ release without inhibiting the Ca2+ pumps or without increasing the
      passive Ca2+ permeability of the endoplasmic reticulum.

PMID- 8255737
TI  - Responses of fatigable and fatigue-resistant fibres of rabbit muscle to low
      frequency stimulation.
AB  - This study investigates early adaptive responses of fast-twitch muscle to
      increased contractile activity by low-frequency stimulation. Changes in
      metabolite levels and activities of regulatory enzymes of carbohydrate metabolism
      were investigated in rabbit tibialis anterior muscle after 24 h of stimulation.
      In addition, changes elicited during a 5-min lasting acute stimulation experiment
      were compared between 24-h-prestimulated and contralateral control muscles.
      Stimulation for 5 min reduced energy-rich phosphates and glycogen, and increased
      lactate in the control muscle. A transient elevation of fructose 2,6-bisphosphate
      demonstrated that activation of phosphofructokinase 2 was an immediate response
      to contractile activity. Prestimulated muscles displayed nearly normal values for
      ATP, phosphocreatine and glycogen, and did not augment lactate. Increased
      activities of hexokinase and phosphofructokinase 2 and permanently elevated
      levels of fructose 2,6-bisphosphate pointed to enhanced glycolysis with glucose
      as the main fuel in the prestimulated muscle. Isometric tension of the control
      muscle decreased rapidly a few minutes after the onset of stimulation. In the
      prestimulated muscles, tension was almost stable, but amounted to only 30%-40% of
      the initial tension of the control muscle. In view of the fibre type distribution
      of rabbit tibialis anterior, these findings suggested that a large fibre fraction
      of the prestimulated muscle, possibly the glycolytic type IID fibres, did not
      contract. Therefore, the possibility must be considered that the metabolite
      pattern of the 24-h-stimulated muscle primarily reflected metabolic activities of
      the contracting, less fatigable fibres, most likely type IIA and type I
      fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255738
TI  - Phosphorylation enhances inactivation of N-type calcium channel current in
      bullfrog sympathetic neurons.
AB  - We have investigated the effects of phosphatase and protein kinase inhibitors on
      calcium channel currents of bullfrog sympathetic neurons using the whole cell
      configuration of the patch clamp technique. Intracellular dialysis with the
      phosphatase inhibitors okadaic acid and calyculin A markedly enhanced the decline
      of inward current during a depolarizing voltage step. Tail current analysis
      demonstrated that this was genuine inactivation of calcium channel current, not
      activation of an outward current. The rapidly inactivating current is N-type
      calcium current (blocked by omega-conotoxin and resistant to nifedipine).
      Staurosporine, a nonselective protein kinase inhibitor, prevented the action of
      okadaic acid, suggesting that protein phosphorylation is involved. Under control
      conditions, the time course of inactivation could be described by the sum of two
      exponentials (tau = 150 ms and 1200 ms), plus a constant (apparently
      noninactivating) component, during depolarizations lasting 2 s. Okadaic acid
      induced a rapid inactivation process (tau = 15 ms) that was absent or negligible
      under control conditions, without obvious effect on the two slower time
      constants. As in control cells, inactivation in okadaic-acid-treated cells was
      strongest near -20 mV, with less inactivation at more positive voltages. However,
      inactivation did not depend on calcium influx. Modulation of calcium channel
      activity by phosphorylation may underly the spontaneous shift between
      inactivating and noninactivating modes recently observed for N-type calcium
      channels. Differences in basal phosphorylation levels could also explain why N
      type calcium channels, originally described as rapidly and completely
      inactivating, inactivate slowly and incompletely in many neurons.

PMID- 8255739
TI  - The enhancement of catecholamine-induced Cl- current by cyclic GMP revealed using
      photolabile caged compounds in guinea-pig ventricular cells.
AB  - Whole cell currents were recorded in single myocytes dissociated from guinea-pig
      ventricles, and caged compounds were loaded intracellularly through the patch
      electrodes. Flash photolysis of caged cyclic GMP (cGMP) increased the amplitudes
      of both catecholamine-induced Cl- (ICl) and Ca2+ currents (ICa) which were pre
      activated by submaximum doses of isoprenaline. Transient activation of ICl by
      photo-release of cyclic AMP (cAMP) showed a half decay time (t1/2) of 16.7 +/-
      1.4 sec (mean +/- S.E.M., n = 14). This decay was markedly delayed by inhibiting
      phosphodiesterases using 3-isobutyl-1-methyl-xanthine (IBMX). The intracellular
      application of cGMP (10-50 microM) also prolonged the decay of the ICl response
      to caged cAMP (t1/2 = 38.0 +/- 7.1 sec, n = 12). These findings strongly support
      the hypothesis that cGMP facilitates the beta-adrenergic response of ionic
      currents through the inhibition of phosphodiesterase in mammalian cardiac
      myocytes.

PMID- 8255740
TI  - Interleukin-1 receptor antagonist in newborn babies and pregnant women.
AB  - We have investigated the possible role of the interleukin-1 receptor antagonist
      (IL-1ra) in the attenuated fever response in the newborn. Umbilical cord blood
      was collected from normal full-term infants (n = 12), and venous blood was
      obtained from afebrile, non-pregnant adults, of both genders (n = 12) and women
      in late pregnancy (n = 12). Plasma IL-1ra, and IL-1ra produced in vitro by
      peripheral blood monocytes stimulated with IL-1 alpha or LPS, were assayed by
      ELISA. Significantly higher concentrations of IL-1ra (P < 0.01, t test) were
      found in umbilical cord plasma than in plasma of non-pregnant adults. Furthermore
      concentrations of IL-1ra in the plasma of women in late pregnancy were
      significantly higher than in the plasma of neonates and non-pregnant adults (P <
      0.01, Mann-Whitney rank-sum test). Neonatal monocytes failed to produce
      significant amounts of IL-1ra upon stimulation in vitro. The monocytes of
      pregnant women produced much higher concentrations of IL-1ra than the monocytes
      of non-pregnant adults (P < 0.01 Mann-Whitney rank-sum test). We speculate that
      IL-1ra may attenuate the febrile response to Gram-negative pyrogens in women in
      late pregnancy, and by crossing the placenta, also in the newborn.

PMID- 8255741
TI  - The benzazepine/benzothiazepine binding domain of the cardiac L-type Ca2+ channel
      is accessible only from the extracellular side.
AB  - The whole-cell tight seal recording technique was used to investigate location of
      benzothiazepine binding site of the cardiac L-type Ca2+ channel. For this we
      utilized a permanently charged compound, SQ 32.428, out of a series of
      benzazepine drugs which have been characterized as competitive inhibitors of
      diltiazem binding. The non-permanently charged derivative SQ 32.910 was initially
      tested to electrophysiologically establish Ca2+ antagonistic properties of
      benzazepines. Upon extracellular application, either compound was able to
      completely block Ca2+ currents. At a stimulating frequency of 0.2 Hz IC50
      concentrations of SQ 32.910 and SQ 32.428 were determined as 35 nM and 15 microM,
      respectively. Intracellular application of SQ 32.428 was then compared to control
      experiments in the absence of drug. Initially, adequate drug dialysis was
      confirmed with 100 microM D890, which produced a progressive inhibition of Ca2+
      currents within 10 min after whole-cell access. In contrast, internal application
      of 100 microM SQ 32.428 did not change time-course of Ca2+ currents compared to
      control run-down. These results show that the benzazepine/benzothiazepine binding
      domain of the cardiac L-type Ca2+ channel is accessible only from the
      extracellular side and therefore suggest an extracellular location on the alpha 1
      subunit of the Ca2+ channel protein.

PMID- 8255742
TI  - Erythrocyte osmotic resistance during acute hypothermia in awake unrestrained
      rats.
AB  - Erythrocyte osmotic fragility and plasma ionic composition were studied in rats
      subjected to acute hypothermia. A decrease in osmotic fragility and a significant
      increase in plasma magnesium and total phosphorus were observed in blood from
      hypothermic rats in relation to control. A decrease in erythrocyte osmotic
      fragility from hypothermic animals was observed when the test was performed at 37
      degrees C, whereas osmotic fragility was unaltered if the test was carried out at
      body temperature. This could be interpreted as an adaptative response to
      counteract the opposite effect on erythrocyte osmotic fragility observed at low
      temperature 'in vitro'.

PMID- 8255743
TI  - Ca2+, Mg2+ and K+ transport in the cortical and medullary thick ascending limb of
      the rat nephron: influence of transepithelial voltage.
AB  - Isolated segments of rat cortical (cTAL) and medullary (mTAL) thick ascending
      limbs were microperfused and the transepithelial net fluxes (JX) were determined
      by measuring the composition of the collected fluid with an electron microprobe.
      When perfused with symmetrical solutions both segments showed similar JNa and JCl
      and lumen-positive transepithelial voltage (Vte = 7-8 mV). JMg, JCa and JK were
      not significantly different from zero. When perfused with asymmetrical solutions
      (lumen 50 mM, bath 150 mM NaCl), the mean Vte were 23 mV and 17 mV in the cTAL
      and mTAL respectively; this rise was accompanied by significant increases in JMg
      and JCa in the cTAL, but not in the mTAL, and a marked increase in JK in both
      segments. It is concluded that, in the rat, divalent cations can be reabsorbed in
      the cTAL, and K+ can be reabsorbed in the cTAL and mTAL. The transport is voltage
      dependent. The mTAL can reabsorb neither Mg2+ nor Ca2+, whatever Vte.

PMID- 8255744
TI  - [Ultrasonographic diagnosis of breast diseases: a review of diagnostic criteria
      of sonomammography on a real-time scanner].
AB  - Fifteen sonomammographic findings of 341 histologically proved breast masses were
      reviewed to improve and objectify the current diagnostic criteria of
      sonomammography enacted by the Japan Society of Ultrasonics in Medicine. The
      author suggested revised diagnostic criteria and a method of evaluating benign or
      malignant breast masses on a real time scanner, especially an electronic linear
      scanner, and presented an original diagnostic concept based particularly on shape
      and internal echo. By examining sensitivity, specificity and accuracy, shape,
      border and internal echo were set up as major criteria, while boundary echo,
      posterior echo, DW ratio, transverse direction, anterior borderline and posterior
      borderline were set up as minor criteria. If two or more major criteria or one
      major and two or more minor criteria are found, the breast mass is diagnosed as
      malignant, whereas if one major and one or no minor criteria, or only three or
      fewer minor criteria are recognized, the mass is diagnosed as benign. This
      diagnostic approach demonstrated a sensitivity of 93.2%, specificity of 85.9%,
      and accuracy of 89.7%, which were superior to current diagnostic criteria for the
      differential diagnosis of breast masses.

PMID- 8255745
TI  - [CT assessment of residual contrast medium in the kidney 12-24 hours after
      angiography].
AB  - Residual contrast medium in the kidney on delayed film is sometimes reported in
      patients with problems in the urinary system following the administration of
      contrast medium. However, we frequently found residual contrast medium in the
      kidney of patients with normal renal function on delayed CT after angiography.
      Thus we carried out CT examination 12-24 hours after angiography with four kinds
      of contrast media to prospectively study the incidence of residual contrast
      medium in the kidney. Residual contrast medium in the kidney was observed on
      delayed CT in 286 of 536 patients (53%). We found a relatively higher incidence
      with ioxaglate (63%) and iohexol (60%) than that with iopamidol (28%) and
      diatrizoate (38%). The incidence of residual contrast medium in the kidney
      increased with the dose of contrast medium administered except in the case of
      iopamidol. The influence of hepatobiliary and renal function on residual contrast
      medium in the kidney was examined. We found a higher incidence of residual
      contrast medium in the group with abnormal hepatobiliary function than in the
      group with normal function. This implied that the hepatobiliary pathway is an
      important tract in the excretion of contrast medium even if the dose of excretion
      is small. A high frequency of residual contrast medium in the kidney was
      recognized on delayed CT not only in the renal dysfunction group but also in the
      normal renal function group. We suggest that residual contrast medium in the
      kidney is a normal phenomenon on delayed CT.

PMID- 8255746
TI  - [An application of dynamic CT for diagnosis of abnormal external ocular muscle
      movement].
AB  - To evaluate the movements of retrobulbar structures radiologically, we have
      developed a new technique called "external ocular muscle movement CT" (EOM CT),
      in which dynamic CT scanning is performed while the patient performs controlled
      eye movements. This new technique was applied in one volunteer and 72 patients
      with external ophthalmoplegia due to orbital mass lesion, hyperthyroid
      ophthalmopathy, blowout fracture, and other retrobulbar lesions. EOM CT permits
      the assessment of extraocular muscle contraction in cases of blowout fracture,
      the evaluation of muscular contraction in hypertrophy of the extraocular muscles,
      and the diagnosis of adhesions between the extraocular muscles and intraorbital
      masses. Radiation dose to the lens from EOM CT was measured using a phantom and
      TLD, and was compared with that of conventional CT scanning with a 5 mm slice
      thickness. The dose to the lens from EOM CT was three times higher than that for
      conventional CT in axial scanning, but in the coronal section of the retrobulbar
      region, the dose to the lens from EOM CT decreases to one twelfth that of
      conventional CT. EOM CT promises to be a powerful modality for functional
      evaluation of the extraocular muscles and other retrobulbar structures.

PMID- 8255747
TI  - [Differentiation of benign from malignant pulmonary nodules with the digital
      analysis of computed radiography].
AB  - To differentiate benign pulmonary nodules from malignant nodules, digital
      analysis of computed radiography (CR) was performed retrospectively. A total of
      142 histologically or clinically proved cases were studied. Digital analysis was
      performed using the method of gradient processing reported by Sherrier et al.
      Gradient number with and without background trend correction and gradient number
      corrected by L-value were obtained from the raw data of CR. The mean gradient of
      93 malignant nodules was significantly different from that of 49 benign nodules.
      The analysis of gradient number without background trend correction and L-value
      correction was most sensitive. Seven radiologists evaluated these nodules as to
      benign or malignant, status, degree of calcification and homogeneity. A
      correlation was found between the detectability of benign nodules and degree of
      calcification. In conclusion, CR-gradient analysis is useful as a screening test
      to differentiate benign nodules from malignant ones.

PMID- 8255748
TI  - [CT and MR imaging of post-aortic left brachiocephalic vein].
AB  - The usefulness of CT and MR imaging (MRI) for the diagnosis of post-aortic left
      brachiocephalic vein (PALBV) is discussed. The subjects of the present study
      consisted of five patients with PALBV, two males and three females, aged four
      months to sixty years. Chest CT and MRI were performed as a follow-up study of
      other intrathoracic lesions in two cases, and for further examination of
      congenital heart diseases in two infant cases. The other patient underwent both
      CT and MRI to evaluate sporadic chest pain. Therefore, all PALBV were found
      incidentally. PALBV passes below the aortic arch in front of the trachea,
      draining the superior vena cava behind the ascending aorta. This finding was
      particularly well documented on consecutive coronal sections on MRI. In patients
      with intrathoracic malignant or specific inflammatory lesion, differentiation
      between PALBV and lymphadenopathy is necessary for treatment. From our
      experience, marked enhancement on CT and no signal intensity on MRI in PALBV
      could differentiate this anomaly from mediastinal lymphadenopathy. In two
      infantile cases with congenital cardiovascular anomalies such as tetralogy of
      Fallot, right aortic arch and pulmonary arterial stenosis, MRI was found to be
      superior to CT in demonstrating these anomalies.

PMID- 8255749
TI  - [Basic study of bone mineral density in os calcis by single energy X-ray
      absorptiometry].
AB  - We studied bone mineral density (BMD) in the os calcis by means of single energy
      X-ray absorptiometry (SXA), and BMD in the third lumbar spine by means of dual
      energy X-ray absorptiometry (DXA), results were as follows. (1) The doses
      absorbed in SXA at the exposure site and the opposite site were measured by
      thermoluminescent dosimetry. The dose absorbed in SXA may be lower than that in
      DXA. (2) The BMD of the os calcis was measured in 30 female volunteers by SXA and
      that of the third lumbar spine by DXA, and age, weight, height, and consequences
      of physical exertion were investigated. BMD as determined by SXA was
      significantly correlated with that determined by DXA (r = 0.65). BMD as
      determined by SXA and DXA tended to decrease with age, to increase with height
      and weight, and to be significantly higher in those who made some physical
      exertion. In conclusion, SXA may be a useful method for the measurement of BMD.

PMID- 8255750
TI  - [Evaluation of the potential benefit of computer-aided diagnosis (CAD) for lung
      cancer screenings using photofluorography: analysis of an observer study].
AB  - To evaluate the potential benefit of computer-aided diagnosis (CAD) in lung
      cancer screenings using photofluorographic films, we performed an observer test
      with 12 radiologists. We used 60 photofluorographic films obtained from a lung
      cancer screening program in Yamaguchi Prefecture (30 contained cancerous nodules
      and 30 had no nodules). In these cases, our current automated detection scheme
      achieved a sensitivity of 80%, but yielded an average of 11 false-positives per
      image. The observer study consisted of three viewing conditions: 1) only the
      original image (single reading), 2) the original image and computer output
      obtained from the current CAD scheme (CAD 1), 3) the original image and computer
      output obtained from a simulated improved CAD scheme with the same 80% true
      positive rate, but with an average of one false-positive per image (CAD 2).
      Compared with double reading using independent interpretations, which is based on
      a higher score between two single readings, CAD 2 was more sensitive in subtle
      cases. The specificity of CAD was superior to that of double reading. Although
      CAD 1 (Az = 0.805) was inferior to double reading (Az = 0.837) in terms of the
      ROC curve, CAD 2 (Az = 0.872) significantly improved the ROC curve and also
      significantly reduced observation time (p < 0.05). If the number of false
      positives can be reduced, computer-aided diagnosis may play an important role in
      lung cancer screening programs.

PMID- 8255751
TI  - Evolutionary relationships among group II intron-encoded proteins and
      identification of a conserved domain that may be related to maturase function.
AB  - Many group II introns encode reverse transcriptase-like proteins that potentially
      function in intron mobility and RNA splicing. We compared 34 intron-encoded open
      reading frames and four related open reading frames that are not encoded in
      introns. Many of these open reading frames have a reverse transcriptase-like
      domain, followed by an additional conserved domain X, and a Zn(2+)-finger-like
      region. Some open reading frames have lost conserved sequence blocks or key amino
      acids characteristic of functional reverse transcriptases, and some lack the
      Zn(2+)-finger-like region. The open reading frames encoded by the chloroplast
      tRNA(Lys) genes and the related Epifagus virginiana matK open reading frame lack
      a Zn(2+)-finger-like region and have only remnants of a reverse transcriptase
      like domain, but retain a readily identifiable domain X. Several findings lead us
      to speculate that domain X may function in binding of the intron RNA during
      reverse transcription and RNA splicing. Overall, our findings are consistent with
      the hypothesis that all of the known group II intron open reading frames evolved
      from an ancestral open reading frame, which contained reverse transcriptase, X,
      and Zn(2+)-finger-like domains, and that the reverse transcriptase and Zn(2+)
      finger-like domains were lost in some cases. The retention of domain X in most
      proteins may reflect an essential function in RNA splicing, which is independent
      of the reverse transcriptase activity of these proteins.

PMID- 8255752
TI  - The retinoblastoma protein binds E2F residues required for activation in vivo and
      TBP binding in vitro.
AB  - The retinoblastoma (RB) tumour suppressor protein is capable of repressing the
      activity of promoters containing DNA binding sites for the transcription factor
      E2F. Recently a protein which binds RB and possesses the DNA binding
      characteristics of E2F has been cloned. Here we show that the E2F activation
      domain is the target for RB-induced repression. RB can silence the 57 residue E2F
      activation domain but cannot effectively repress an E2F mutant which has reduced
      RB binding capacity. Extensive mutagenesis of E2F shows residues involved in RB
      binding are required for transcription activation. Mutations which affect both
      functions most dramatically lie within the minimal RB binding region. A further
      subset of sensitive residues lies within a new repeat motif E/DF XX L X P which
      flanks the minimum RB binding site. These data show that RB can mask E2F residues
      involved in the activation process, possibly by mimicking a component of the
      transcriptional machinery. Consistent with this model, we find that the TATA box
      binding protein TBP can bind to the E2F activation domain in vitro in a manner
      indistinguishable from that of RB.

PMID- 8255753
TI  - Deuteriation of sugar protons simplify NMR assignments and structure
      determination of large oligonucleotide by the 1H-NMR window approach.
AB  - The concept of the 1H-NMR window has been developed and examined through a
      comparative study of NOESY spectra of a self-complementary Dickerson's dodecamer
      (I) [5'd(5C6G7C8G9A10A11T12T13C-14G15C16G)2(3')], a self-complementary 20-mer
      (II) [(5'd(1C2G3C4G5C6G7C8G9A10A11T12T13C14G15C16G17C18G19C20G)2(3')] in which
      the core part consists of the same Dickerson's dodecamer sequence with the
      flanking CGCG residues at both 3' and 5'-ends, and the partly-deuteriated (shown
      by underlined CGCG residues at both 3' and 5'-ends) analogous duplex (III)
      [5'd(1C2G3C4G5C6G7C8G9A10A11T12T13C14G15C16G17C18G19C20G)2(3')] in which the core
      5C to 16G part (i.e. 1H-NMR window) consists of the natural Dickerson's dodecamer
      sequence. A comparison of their NOESY spectra clearly demonstrates that the
      severe overlap of proton resonances in the larger DNA duplex (II) has been
      successfully reduced in the partly-deuterated duplex (III) as a result of
      specific incorporations of the sugar-deuteriated nucleotide residues in the
      latter [stereospecific > 97 atom % 2H enrichment at H2', H2'' and H3' sites,
      approximately 85 atom % 2H enrichment at H4' and approximately 20 atom % 2H
      enrichment at H1' (see refs. 10 and 11) in the 20-mer duplex (III)]. These
      simplifications of the resonance overlap by the deuteriation approach have
      enabled unequivocal chemical shift assignments and extraction of the quantitative
      NOE data in the 1H-NMR window part of duplex (III). A comparison of the 12
      nucleotide long 1H-NMR window in (III) with that of the 12-mer duplex (I) also
      shows the scope of studying the changes in conformation and dynamics of the core
      12-mer region in (III) which result from the increase of molecular weight due to
      the DNA chain extension. It is noteworthy that such a study is clearly impossible
      for the natural 20-mer (II) because of the inherent problem of the overlap of
      resonances.

PMID- 8255754
TI  - A tRNA gene transcription initiation site is similar to mRNA and rRNA promoters
      in plant mitochondria.
AB  - The gene for tRNA(Phe) is located 292 nucleotides upstream of the tRNA(Pro) gene
      in the Oenothera mitochondrial genome. Hybridization with in vitro capped primary
      transcripts indicates a transcription initiation site in the 5' region of the
      gene for tRNA(Phe). Primer extension experiments show the presence of precursor
      transcripts covering tRNA(Phe) and adjacent sequences up to a transcription
      initiation site 181 or 180 nucleotides upstream of the tRNA gene. The genomic
      sequence at this transcription initiation site contains the consensus motif
      derived for putative promoters of mitochondrial protein and rRNA coding genes in
      dicotyledonous plants. This sequence similarity suggests that tRNAs, rRNAs and
      mRNAs can be transcribed from homologous promoters in plant mitochondria.

PMID- 8255755
TI  - In vivo selection of randomly mutated retroviral genomes.
AB  - Darwinian evolution, that is the outgrowth of the fittest variants in a
      population, usually applies to living organisms over long periods of time.
      Recently, in vitro selection/amplification techniques have been developed that
      allow for the rapid evolution of functionally active nucleic acids from a pool of
      randomized sequences. We now describe a modification of the nucleic acid
      evolution protocol in which selection and amplification take place inside living
      cells by means of a retroviral-based replication system. We have generated a
      library of HIV-1 DNA genomes with random sequences in particular domains of the
      TAR element, which is the binding site for the Tat trans-activator protein. This
      mixture of HIV genomes was transfected into T cells and outgrowth of the fittest
      viruses was observed within two weeks of viral replication. The results of this
      in vivo selection analysis are consistent with the notion that primary sequence
      elements in both TAR bulge and loop domains are critical for Tat-mediated trans
      activation and viral replication.

PMID- 8255756
TI  - The structure of the initiation complex at the replication origin, oriC, of
      Escherichia coli.
AB  - Two distinct regions in the replication origin, oriC, of Escherichia coli are
      separately distorted upon initiation complex formation by the initiator protein
      DnaA. The AT-rich region in the left part of oriC and the start site region in
      the right part of oriC. Chemical modification of single-stranded DNA was observed
      at both regions whereas endonuclease recognition of DNA mini-bulges specifically
      occurred in the start site region. We show that the helical phasing of binding
      sites for DnaA protein in oriC is important for origin function. An insertion or
      deletion of one helical turn between the two rightmost binding sites does not
      alter the efficiency of replication initiation, whereas all modifications of
      distance by less or more than one helical turn result in inactivation of oriC.
      DnaA binding and helical distortions in the AT-rich region as well as in the
      start site region are not affected in the distance mutants irrespective of their
      functionality in vivo. We propose a specific compact nucleoprotein structure for
      the initiation complex.

PMID- 8255757
TI  - Homologous recombination in plant cells is enhanced by in vivo induction of
      double strand breaks into DNA by a site-specific endonuclease.
AB  - Induction of double strand breaks (DSBs) is coupled to meiotic and mitotic
      recombination in yeast. We show that also in a higher eukaryote induction of DSBs
      is directly correlated with a strong enhancement of recombination frequencies. We
      cotransfected Nicotiana plumbaginifolia protoplasts with a plasmid carrying a
      synthetic I-SceI gene, coding for a highly sequence specific endonuclease,
      together with recombination substrates carrying an I-SceI-site adjacent to their
      homologous sequences. We measured efficiencies of extrachromosomal recombination,
      using a well established transient beta-glucuronidase (GUS) assay. GUS enzyme
      activities were strongly increased when a plasmid carrying the I-SceI gene in
      sense but not in antisense orientation with respect to the promoter was included
      in the transfections. The in vivo induced DSBs were detected in the recombination
      substrates by Southern blotting, demonstrating that the yeast enzyme is
      functional in plant cells. At high ratios of transfected I-SceI-genes to I-SceI
      sites the majority of the I-SceI-sites in the recombination substrates are
      cleaved, indicating that the induction of the DSBs is the rate limiting step in
      the described recombination reaction. These results imply that in vivo induction
      of transient breaks at specific sites in the plant genome could allow foreign DNA
      to be targeted to these sites via homologous recombination.

PMID- 8255759
TI  - Proteolytic degradation of MAD3 (I kappa B alpha) and enhanced processing of the
      NF-kappa B precursor p105 are obligatory steps in the activation of NF-kappa B.
AB  - We have studied the role of protein turnover in the induction of NF-kappa B DNA
      binding activity. Treatment of cells with tumour necrosis factor (TNF), double
      stranded RNA (dsRNA), or phorbol esters is shown to be associated with an
      increase in the rate of p105 to p50 processing, and the loss of immunologically
      detectable MAD3/I kappa B alpha. Phosphate-labelling experiments indicate that
      these events are preceded by the phosphorylation of MAD3 and p105. The protease
      inhibitors TLCK (N alpha-p-Tosyl-L-Lysine Chloromethyl Ketone) and TPCK (N alpha
      p-Tosyl-L-Phenylalanine Chloromethyl Ketone) inhibit both p105 to p50 processing
      and MAD3 degradation, and also cause a complete block to NF-kappa B activation.
      These data suggest a model for NF-kappa B activation in which phosphorylation
      destabilises the NF-kappa B/MAD3 complex but that, in vivo, this is insufficient
      to lead to activation in the absence of an obligatory mechanism that degrades
      MAD3.

PMID- 8255758
TI  - The Drosophila copia retrotransposon contains binding sites for transcriptional
      regulation by homeoproteins.
AB  - We have identified in the 5' untranslated region of the Drosophila copia
      retrotransposon, 3' to the left LTR, a sequence for transcriptional regulation by
      homeoproteins. Co-transfection assays using expression vectors for homeoproteins
      and reporter vectors containing the lacZ gene under the control of either the
      entire copia LTR with 5' untranslated sequence, or a minimal heterologous
      promoter flanked with a 130 bp fragment containing the copia untranslated region,
      disclosed both positive and negative modulations of promoter activity in
      Drosophila cells in culture: a 5-10 fold decrease with engrailed, even-skipped
      and zerknullt in DH33 cells, and a 10-30 fold increase with fushi tarazu and
      zerknullt in Schneider II cells. In all cases, the regulatory effects were
      abolished with reporter plasmids deleted for a 58 bp fragment encompassing the
      putative homeoprotein binding sites. Mobility shift assays with a purified
      homeodomain-containing peptide demonstrated direct interaction with the 58 bp
      fragment, with an affinity in the 1-10 nM range as reported with the same peptide
      for other well characterized homeodomain binding regulatory sites. Foot-printing
      experiments with the extended LTR demonstrated protection of 'consensus'
      sequences, located within the 58 bp fragment. These homeodomain binding sites
      could be involved in the developmental regulation of the copia retrotransposon.

PMID- 8255760
TI  - Molecular cloning of a zinc finger protein which binds to the heptamer of the
      signal sequence for V(D)J recombination.
AB  - The somatic V(D)J recombination for the assembly of the Ig and TCR genes is
      mediated by the recombination signal sequences (Rss) and the V(D)J recombinase. A
      cDNA clone was isolated from a lambda gt11 expression library made from mouse
      thymocyte poly(A)+ RNA, using the Rss as a ligand. The deduced amino acid
      sequence of the putative protein, designated Recognition component (Rc), reveals
      a pair of Cys2-His2 zinc fingers followed by a Glu- and Asp-rich acidic domain.
      In addition, there are five copies of the Ser/Thr-Pro-X-Arg/Lys sequence, which
      are putative DNA binding units. The zinc finger-acidic domain structures present
      in Rc are also found in several enhancer binding proteins, such as those for the
      kappa B motif of the Ig kappa light chain enhancer or related sequences.
      Bacterial fusion proteins for Rc bind preferentially to the Rss heptamer and to
      the kappa B motif. The dual affinities of Rc for the Rss heptamer and the kappa B
      motif suggest a possible link between Ig transcription and somatic recombination.
      The formation of multiple 'gel-shifted' DNA-protein complexes for Rc and its DNA
      ligand suggests that these complexes tend to multimerize.

PMID- 8255761
TI  - Anticodon bases C34 and C35 are major, positive, identity elements in
      Saccharomyces cerevisiae tRNA(Trp).
AB  - A single form of tRNA(Trp) exists in the yeast cytoplasm to respond to the unique
      codon, UGG, which specifies this amino acid. Mutations in the anticodon of the
      corresponding gene, which generate potential nonsense suppressor tRNAs, have been
      generated in vitro and tested in vivo for biological activity. The amber (C35U)
      and opal (C34U) suppressors show strong and weak activities respectively while
      the ochre suppressor (C34U,C35U) has no detectable biological activity. To
      understand the basis for these differences, a set of synthetic tRNA(Trp) genes
      has been constructed to permit in vitro, T7 RNA polymerase synthesis of
      transcripts corresponding to the normal and mutant tRNAs. Kinetic parameters for
      aminoacylation of these transcripts by purified, yeast, tryptophanyl-tRNA
      synthetase have been measured and compared to values observed using the naturally
      occurring tRNA(Trp) as a substrate. The efficiency of aminoacylation is reduced
      by 40, 2000, and 30,000 fold by the C35U, C34U, and C34U,C35U mutations
      respectively. Interestingly, the C35U change affects only tRNA binding while C34U
      also alters catalytic efficiency. We conclude that both C34 and C35 are major
      identity elements in the recognition of tRNA(Trp) by its cognate synthetase.
      These differences in aminoacylation efficiency closely parallel the in vivo
      suppressor activities of the mutants.

PMID- 8255762
TI  - Specific cleavage of transcription factors by the thiol protease, m-calpain.
AB  - The intracellular nonlysosomal calcium-dependent cysteine protease, m-calpain, is
      shown to specifically cleave the bHLHzip transcription factor USF leaving the
      binding and dimerisation domains intact. The resultant protein is capable of
      efficient DNA binding but is no longer able to activate transcription. A
      surprisingly high proportion of other transcription factors tested, AP1 (c-Fos/c
      Jun), Pit-1, Oct-1, CP1a and b, c-Myc, ATF/CREB, AP2 and AP3 but not Sp1, were
      similarly cleaved by m-calpain to produce specific partial digestion products.
      These properties make m-calpain a particularly useful protease for proteolytic
      studies of transcription factors and also raise the possibility that m-calpain
      may be involved in vivo in regulation of turnover or transcriptional activity of
      a number of transcription factors.

PMID- 8255763
TI  - SIN1 interacts with a protein that binds the URS1 region of the yeast HO gene.
AB  - Evidence has recently been mounting suggesting that a number of chromatin
      components previously thought to primarily or exclusively have structural
      function, also have a regulatory role in eukaryotic transcription. Notably, in
      yeast, histone H4 N-terminal sequence has been shown to be required for promoter
      activation of certain genes in vivo, and mutations in histone H3 (SIN2) or in
      SIN1 (which has some sequence similarity to HMG1) are able to suppress swi1,
      swi2, and swi3 mutations, restoring transcription to HO as well as a number of
      other genes. In this paper we report the identification of a novel protein or
      protein complex that specifically binds a short sequence in the HO regulatory
      region on the one hand, and on the other somehow appears to contact the SIN1
      protein. We have shown that the DNA binding activity itself does not contain
      SIN1, since extracts from sin1 delta strains retain the activity. Interestingly,
      extracts made from cells carrying the dominant sin1-2 point mutation lack the
      binding activity. Furthermore, bacterially produced sin1-2 protein can dissociate
      a DNA/protein complex while a similarly produced SIN1 protein has no effect on
      the complex at similar concentrations. When the DNA sequence to which the protein
      complex binds is placed in a CYC1 promoter lacking a UAS (upstream activating
      sequence), it can serve as a weak UAS in a SIN1 dependent way. Our data imply
      that a sequence specific DNA binding protein(s) may mediate between the SIN1
      protein and the basal transcription apparatus transcribing HO.

PMID- 8255764
TI  - Reconstitution of mammalian excision repair activity with mutant cell-free
      extracts and XPAC and ERCC1 proteins expressed in Escherichia coli.
AB  - Nucleotide excision repair in humans involves the coordinated actions of 8-10
      proteins. To understand the roles of each of these proteins in excision it is
      necessary to develop an in vitro excision repair system reconstituted entirely
      from purified proteins. Towards this goal we have expressed in E. coli two of the
      8 genes known to be essential for the excision reaction. XPAC and ERCC1 were
      expressed as fusion proteins with the Escherichia coli maltose binding protein
      (MBP) and purified to > 80% homogeneity by affinity chromatography. The purified
      proteins either as fusions or after cleavage from the MBP were able to complement
      the CFE of cells with mutations in the corresponding genes in an excision assay
      with thymine dimer containing substrate.

PMID- 8255765
TI  - Coincidence painting: a rapid method for cloning region specific DNA sequences.
AB  - We have developed a novel coincidence cloning strategy, termed Coincidence
      Painting, which enables the rapid generation of large numbers of region specific
      sequences. Coincidence Painting utilises Degenerate Oligonucleotide Primed PCR
      (DOP-PCR) amplification of flow sorted derivative translocation chromosomes. The
      PCR products are hybridised in situ onto specific flow sorted chromosomes for
      coincident sequence selection. Eluted and reamplified material is then cloned
      using a novel insert end revelation and ligation technique. Cloned inserts range
      in size from 150-1300 bps of which approximately 54% appear to be single copy
      sequences. The cloning method permits the excision of vector free probe for
      library hybridisation screening and the small insert size facilitates analysis
      for the generation of sequence tagged sites (STSs). We have used such clones
      successfully for YAC screening by PCR and for cosmid screening by filter
      hybridisation. This new methodology should allow the rapid saturation with probes
      of regions defined by specific translocation breakpoints.

PMID- 8255766
TI  - Novel internal promoter/enhancer of HTLV-I for Tax expression.
AB  - The transcription initiation signals in retroviruses lie within the long terminal
      repeat (LTR) sequences. We have found a new transcriptional promoter in a central
      portion of the genome of human T-cell leukaemia virus type I (HTLV-I). The
      transcription start site is located just upstream to the ATG codon of the
      transcriptional trans-activator molecule, tax protein (Tax). The internal
      promoter may provide a new insight into gene expression of HTLV-I. The mechanism
      of leukaemogenesis by the defective HTLV-I is also discussed. Furthermore, we
      have identified two repeats of a novel enhancer sequence AGTTCT, which are
      located around the initiation site. We call the sequence HIRE (HTLV-I Internal
      Regulatory Element).

PMID- 8255767
TI  - Purification and characterization of human autoantibodies directed to specific
      regions on U1RNA; recognition of native U1RNP complexes.
AB  - Antibodies against naked U1RNA can be found in sera from patients with overlap
      syndromes of systemic lupus erythematosus (SLE) in addition to antibodies
      directed to the proteins of U1 ribonucleoproteins (U1RNP). We investigated the
      reactivity of these U1RNA specific autoantibodies with the native U1RNP particle
      both in vitro and inside the cell. For this purpose a method was developed to
      purify human autoantibodies directed to specific regions of U1RNA. The antibodies
      are specifically directed to either stemloop II or stemloop IV of U1RNA and do
      not crossreact with protein components of U1RNP. Both types of antibody are able
      to precipitate from cell extracts native U1snRNPs containing most, if not all,
      protein components. Immunofluorescence patterns indicate that the antigenic sites
      on the RNA, i.e. the stem of stemloop II and the loop of stemloop IV, are also
      available after fixation of the cells. Immunoelectron microscopy employing anti
      stemloop IV antibodies and purified, complete U1snRNP particles showed that
      stemloop IV is located within the body of the U1RNP complex, which also comprises
      the Sm site and the common Sm proteins. The anti-U1RNA autoantibodies described
      in this paper recognize native U1RNP particles within the cell and can therefore
      be used as tools to study mechanisms involved in splicing of pre-mRNA.

PMID- 8255768
TI  - Influence of nearest neighbor sequence on the stability of base pair mismatches
      in long DNA; determination by temperature-gradient gel electrophoresis.
AB  - Temperature-gradient gel electrophoresis (TGGE) was employed to determine the
      thermal stabilities of 48 DNA fragments that differ by single base pair
      mismatches. The approach provides a rapid way for studying how specific base
      mismatches effect the stability of a long DNA fragment. Homologous 373 bp DNA
      fragments differing by single base pair substitutions in their first melting
      domain were employed. Heteroduplexes were formed by melting and reannealing pairs
      of DNAs, one of which was 32P-labeled on its 5'-end. Product DNAs were separated
      based on their thermal stability by parallel and perpendicular temperature
      gradient gel electrophoresis. The order of stability was determined for all
      common base pairs and mismatched bases in four different nearest neighbor
      environments; d(GXT).d(AYC), d(GXG).d(CYC), d(CXA).d(TYG), and d(TXT).d(AYA) with
      X,Y = A, T, C, or G. DNA fragments containing a single mismatch were destabilized
      by 1 to 5 degrees C with respect to homologous DNAs with complete Watson-Crick
      base pairing. Both the bases at the mismatch site and neighboring stacking
      interactions influence the destabilization caused by a mismatch. G.T, G.G and G.A
      mismatches were always among the most stable mismatches for all nearest neighbor
      environments examined. Purine.purine mismatches were generally more stable than
      pyrimidine.pyrimidine mispairs. Our results are in very good agreement with data
      where available from solution studies of short DNA oligomers.

PMID- 8255769
TI  - Contrasted cis-acting effects of downstream 5' splice sites on the splicing of a
      retained intron: the adenoviral E1A pre-mRNA model.
AB  - The adenoviral E1A pre-mRNA contains an upstream intron (the 216 nucleotide
      intron) which is spliced only weakly both in vivo and in vitro. We have chosen
      the E1A transcript as a model to analyse, in vitro, the role of downstream cis
      elements involved in the alternative splicing of this retained intron. By using a
      series of constructs containing specific deletions, mutations and/or truncations,
      we show that the 13S 5' splice site, positioned 259 nucleotides downstream of the
      216 nucleotide intron, is the main cis-element which activates the splicing of
      this intron. Our results establish the importance of a downstream 5' splice site
      for the activation of the 3' splice site, which is known to be suboptimal within
      this retained intron. Unexpectedly, the 12S 5' splice site, although positioned
      at an ideal distance (121 nucleotides) from the upstream intron, does not exhibit
      such a cis-acting effect. In contrast, its improvement to a consensus sequence
      may even result in a slight negative cis-acting effect in the presence of the 13S
      5' splice site, which is the first observation of such a feature. We have shown
      that this unexpected behaviour is due, at least partly, to the unusual
      characteristics of the wild-type upstream intron, which requires a hairpin
      structure between the branch sites and the 3' splice site to reduce the
      operational distance between these two sites. Possible mechanisms involved in the
      contrasted cis-acting effects of the 13S and 12S 5' splice sites are discussed.

PMID- 8255770
TI  - Discover 1: a new program to search for unusually represented DNA motifs.
AB  - DISCOVER1 (DIStribution COunter VERsion 1) is a new program that can identify DNA
      motifs occurring with a high deviation from the expected frequency. The program
      generates families of patterns, each family having a common set of defined bases.
      Undefined bases are inserted amongst the defined bases in different ways, thus
      generating the diverse patterns of each family. The occurrences of the different
      patterns are then compared and analysed within each family, assuming that all
      patterns should have the same probability of occurrence. An extensive use of
      computer memory, combined with the immediate sorting of counts by address
      calculation allow a complete counting of all DNA motifs on a single pass on the
      DNA sequence. This approach offers a very fast way to search for unusually
      distributed patterns and can identify inexact patterns as well as exact patterns.

PMID- 8255771
TI  - Induction of cleavage in topoisomerase I c-DNA by topoisomerase I enzymes from
      calf thymus and wheat germ in the presence and absence of camptothecin.
AB  - In this study, we further examined the sequence selectivity of camptothecin in
      mammalian topoisomerase I cDNA from human and Chinese hamster. In the absence of
      camptothecin, almost all the bases at the 3'-terminus of cleavage sites are T for
      calf thymus and wheat germ topoisomerase I. In addition, wheat germ topoisomerase
      I exhibits preference for C (or not T) at -3 and for T at -2 position. As for
      camptothecin-stimulated cleavage with topoisomerase I, G (or not T) at +1 is an
      additional strong preference. This sequence selectivity of camptothecin is
      similar to that previously found in SV40 DNA, suggesting that camptothecin
      preferentially interacts with topoisomerase I-mediated cleavage sites where G is
      the base at the 5'-terminus. These results support the stacking model of
      camptothecin (Jaxel et al. (1991) J. Biol. Chem. 266, 20418-20423). Comparison of
      calf thymus and wheat germ topoisomerase I-mediated cleavage sites in the
      presence of camptothecin shows that many major cleavage sites are similar.
      However, the relative intensities are often different. One of the differences was
      attributable to a bias at position -3 where calf thymus topoisomerase I prefers G
      and wheat germ topoisomerase I prefers C. This difference may explain the unique
      patterns of cleavage sites induced by the two enzymes. Sequencing analysis of
      camptothecin-stimulated cleavage sites in the surrounding regions of point
      mutations in topoisomerase I cDNA, which were found in camptothecin-resistant
      cell lines, reveals no direct relationship between DNA cleavage sites in vitro
      and mutation sites.

PMID- 8255772
TI  - Biological origins of long-range correlations and compositional variations in
      DNA.
AB  - The occurrence of certain long-range correlations between nucleotides in DNA
      sequences of living organisms has recently been reported. The biological origin
      of these correlations was unknown. The correlations were proposed to be concerned
      with fractal structure and differences between intron-containing and intron-less
      sequences. We and others have reported that no consistent difference exists
      between intron-containing and intron-less sequences. In agreement with this, we
      demonstrate here that the long-range correlations are trivially equivalent to the
      varying ratio R between pyrimidines and purines (or any other nucleotide
      combinations) in different regions of a DNA sequence. Moreover, we show that this
      variation of R has simple biological explanations: Differences in base
      composition occur along most DNA sequences and are associated with (i) simple
      repeats (ii) differences in codon composition (due to the amino acid composition
      in the encoded protein), (iii) change of the direction of transcription (and thus
      also translation), and (iv) differences between protein- and rRNA-encoding
      segments. Seven biological examples are given.

PMID- 8255773
TI  - Design and specificity of hammerhead ribozymes against calretinin mRNA.
AB  - We obtained a partial sequence of mouse calretinin mRNA from cDNA clones, and
      designed hammerhead ribozymes to cleave positions within it. With a view to
      optimising hammerhead ribozymes for eliminating the mRNA in vivo, we varied the
      length and sequence of the three duplex 'arms' and measured the cleavage of long
      RNA substrates in vitro at 37 degrees C (as well as 50 degrees C). Precise
      cleavage occurred, but it could only go to completion with a large excess of
      ribozyme. The evidence suggests that the rate-limiting step with a large target
      is not the cleavage, but the formation of the active ribozyme: substrate complex.
      The efficiency varied unpredictably according to the target site, the length of
      the substrate RNA, and the length of the ribozyme; secondary structure in vitro
      may be responsible. We particularly investigated the degree of sequence
      specificity. Some mismatches could be tolerated, but shortening of the total
      basepairing with the substrate to less than 14 bp drastically reduced activity,
      implying that interaction with weakly-matched RNAs is unlikely to be a serious
      problem in vivo. These results suggest that specific and complete cleavage of a
      mRNA in vivo should be possible, given high-level expression of a ribozyme
      against a favourable target site.

PMID- 8255774
TI  - Synthesis of a carboxamide linked T*T dimer and its incorporation in
      oligonucleotides.
AB  - The condensation of 5'-O-protected 3'-O-(2-aminoethyl)thymidine with 1,2-dideoxy
      1-thyminyl-beta-D-erythro-pentofuranuronic acid gives a T*T dimer with *
      representing a 3'-OCH2CH2NHC(O)-4' linkage connecting the two pentofuranosyl
      moieties. The incorporation of this dimer in oligonucleotide sequences show only
      moderately lowered Tm values when hybridized with a complementary DNA relative to
      the unmodified DNA duplex. Consistently, no looped-out or bubble-type structure
      could be detected in DNA duplexes with an internal T*T module. Moreover, the 5
      atom carboxamide linker causes complete stop on DNA polymerization and on
      exonuclease III degradation.

PMID- 8255776
TI  - In vivo cloning of PCR products in E. coli.
AB  - This report describes an efficient method to clone PCR products exploiting
      endogenous Escherichia coli enzymatic activities. PCR products are engineered to
      contain terminal sequences identical to sequences at the two ends of a linearized
      vector. PCR products and vector DNA are then simply co-transfected into E. coli
      strain JC8679, obviating the requirement for enzymatic treatment of the PCR
      product or in vitro ligation. The high rate of homologous recombination in this
      strain results in efficient incorporation of the insert into the vector, a
      process we refer to as in vivo cloning (IVC).

PMID- 8255777
TI  - Efficient selection of 3'-terminal exons from vertebrate DNA.
AB  - Identification of expressed sequences within genomic DNA is a hurdle in the
      characterization of complex genomes. We developed an exon trapping scheme that
      provides a positive selection for vertebrate 3'-terminal exons. A copy of the
      trapped exon sequence is obtained by RT/PCR amplification. The technique detects
      valid terminal exons without interference from partial exons or non-specific
      sequences, including simple human repeated sequences. Application to random human
      cosmids yielded one unique trapped terminal exon per cosmid on average. Because
      vertebrate terminal exons average 600-700 nucleotides in length, the technique
      provides transcribed sequences of sufficient length to assist further mapping
      efforts.

PMID- 8255775
TI  - A single amino-acid substitution in the Ets domain alters core DNA binding
      specificity of Ets1 to that of the related transcription factors Elf1 and E74.
AB  - Ets proteins form a family of sequence specific DNA binding proteins which bind
      DNA through a 85 aminoacids conserved domain, the Ets domain, whose sequence is
      unrelated to any other characterized DNA binding domain. Unlike all other known
      Ets proteins, which bind specific DNA sequences centered over either GGAA or GGAT
      core motifs, E74 and Elf1 selectively bind to GGAA corecontaining sites. Elf1 and
      E74 differ from other Ets proteins in three residues located in an otherwise
      highly conserved region of the Ets domain, referred to as conserved region III
      (CRIII). We show that a restricted selectivity for GGAA core-containing sites
      could be conferred to Ets1 upon changing a single lysine residue within CRIII to
      the threonine found in Elf1 and E74 at this position. Conversely, the reciprocal
      mutation in Elf1 confers to this protein the ability to bind to GGAT core
      containing EBS. This, together with the fact that mutation of two invariant
      arginine residues in CRIII abolishes DNA binding, indicates that CRIII plays a
      key role in Ets domain recognition of the GGAA/T core motif and lead us to
      discuss a model of Ets proteins--core motif interaction.

PMID- 8255778
TI  - A truncated herpes simplex virus origin binding protein which contains the
      carboxyl terminal origin binding domain binds to the origin of replication but
      does not alter its conformation.
AB  - We have studied the DNA binding properties of a polypeptide consisting of the
      carboxyl terminal 37% of UL9, the herpes simplex virus type 1 (HSV-1) origin of
      replication binding protein. Using a Sindbis virus expression system, we
      expressed and partially purified this truncated form of UL9 (UL9CT) which
      contains the site-specific DNA binding domain. UL9CT specifically recognized UL9
      binding sites on a 200 base pair DNA fragment containing the HSV origin ori(s)
      and appeared to bind as a dimer to each site. DNAse I footprint analysis showed
      that UL9CT protected the two high affinity binding sites of ori(s), but unlike
      full-length UL9, UL9CT did not induce a conformational change in the origin.
      Addition of anti-UL9CT antibody to the UL9CT-origin complex, however, caused a
      conformational change in the origin to be evident. Our results suggest that a
      domain, or domains, in the amino terminus are necessary for a UL9-induced origin
      conformational change to occur and that UL9-UL9 interactions between binding
      sites are involved.

PMID- 8255779
TI  - Characterization of a multisubunit human protein which selectively binds single
      stranded d(GA)n and d(GT)n sequence repeats in DNA.
AB  - A protein which selectively binds d(GA)n and d(GT)n sequence repeats in single
      stranded DNA has been identified in human fibroblasts. This protein, designated
      PGB, has been purified at least 500-fold by ammonium sulfate precipitation
      followed by DEAE-Sepharose column chromatography and affinity chromatography in a
      column of d(GA)-Sepharose. Electrophoretic mobility shift assays revealed that
      the PGB protein bound most avidly d(GA)n and d(GT)n tracts of n > 5. It also
      bound other G-rich DNA sequence repeats, including dGn tracts, with lower
      affinities. It did not manifest significant binding affinities to single stranded
      M13 DNA, or to the homopolynucleotides poly dA, poly dC and poly dT, or to
      various DNA sequence repeats which do not contain G residues, such as d(A-C)n and
      d(TC)n. It did not bind double stranded d(T-C)n.d(GA)n tracts or other double
      stranded DNA sequences. In glycerol gradient centrifugation assays the d(GA)n-
      and the d(GT)n-binding activities cosedimented as a homogeneous protein species
      having an S20,w = 9.4 +/- 0.7 and an estimated native molecular weight of 190,000
      +/- 7,000. UV crosslinking assays revealed that the protein contains 33.6 +/- 2.1
      kd subunits which bind d(GA)n and d(GT)n sequences. However, SDS-polyacrylamide
      gel electrophoresis of the purified protein followed by silver staining indicated
      that it may also contain other subunits that do not contact the DNA. It is
      proposed that binding of the PGB protein to single stranded d(GA)n or d(GT)n
      tracts in double stranded topologically restricted DNA may stimulate strand
      separation and formation of triple helices or other unusual DNA structures.

PMID- 8255780
TI  - Oncogene activation of HIV-LTR-driven expression via the NF-kappa B binding
      sites.
AB  - The Raf-1 proto-oncogene product is a highly regulated serine/threonine kinase
      that functions in signal transduction downstream from growth factor receptors and
      upstream from nuclear proto-oncogene products. Using a transient cotransfection
      assay we have found that activated Raf-1 activates expression from the HIV-LTR.
      Analysis of a series of 5' deletion and point mutations revealed the NF-kappa B
      motifs as the Raf-responsive element in the HIV-LTR. Moreover, Raf-BXB activated
      expression from heterologous promoters driven by the HIV NF-kappa B binding
      sites. In addition to Raf, we show that v-Src, v-H-Ras and v-Mos activate HIV-LTR
      expression through the NF-kappa B binding sites and v-H-Ras-induced HIV-LTR
      expression is mediated by Raf-1. These findings may have implications for the
      involvement of the cellular homologues of these oncogenes in the switch from
      latent to productive infection by HIV in response to T-cell activation.

PMID- 8255781
TI  - Functional redundancy of octamer elements in the mouse mammary tumor virus
      promoter.
AB  - The promoter of mouse mammary tumor virus contains three overlapping sequence
      elements related to the octamer consensus (ATGCAAAT) that are largely contained
      within two 10 bp direct repeats (CTTATGTAAA) separated by a 2 bp spacer between
      60 and 39 relative to the start of transcription. Gel electrophoresis mobility
      shift competition assays demonstrate that the most distal of these octamer
      related elements is recognized by a protein that also binds to the most proximal
      element, while the central octamer-related element is not efficiently recognized.
      Transient transfection assays with altered promoters reveal that the portion of
      the 10 bp repeat that is not related to the octamer consensus appears not to be
      important for transcription. The distal and proximal octamer-related elements
      are, at least to some extent, functionally redundant. Complete deletion of one
      element has little or no effect on promoter activity so long as certain spacing
      constraints among remaining promoter elements are maintained. Systematic
      variation of such spacing reveals a cyclic effect on promoter activity
      corresponding to the periodicity of Bform DNA, suggesting functional interactions
      between proteins bound to adjacent sites.

PMID- 8255782
TI  - Inhibition of HIV-1 replication by ribozymes that show poor activity in vitro.
AB  - Self-cleaving RNAs (ribozymes) can be engineered to cleave target RNAs of choice
      in a sequence-specific manner (1). Consequently, they could be used to inhibit
      virus replication or to analyse host gene function in vivo. However, ribozymes
      that are catalytic in vitro are generally disappointing when analysed in cells
      unless expressed at high levels relative to their target RNAs (2, 3). Here we
      provide evidence that this can be overcome by optimizing ribozyme structure using
      cellular rather than cell-free assays. We show that ribozymes of relatively long
      flanking complementary regions (FCRs), while poor catalysts in vitro, can produce
      profound inhibition of HIV replication in cells. By examining a series of
      ribozymes in which the FCRs vary from 9 to 564 nucleotides, we establish that the
      optimum length for activity in the cell is > or = 33 nucleotides.

PMID- 8255783
TI  - Polyadenylation site selection cannot occur in vivo after excision of the 3'
      terminal intron.
AB  - Splicing of 3'-terminal introns and polyadenylation of pre-mRNAs can be coupled
      in an appropriate cell-free system. However, definitive evidence has been lacking
      as to whether these events are coupled in vivo and whether the order of these two
      processing events is obligatory. Here, we investigated these questions by
      examining the in vivo processing of transcripts that differ solely by the precise
      insertion of an intron within the first of two polyadenylation signals.
      Quantitative S1 nuclease mapping and PCR techniques were utilized to analyze the
      processed RNAs that accumulated in monkey cells transfected with plasmids
      encoding these transcripts. We found that, whereas all of the primary transcripts
      that lacked the inserted intron were processed via utilization of the 5'-proximal
      polyadenylation signal, none of the transcripts initially disrupted in this
      signal were processed this way even though the disrupting intron had been
      properly excised and excision sometimes preceded polyadenylation. In addition,
      deletion of the second polyadenylation signal resulted in failure of spliced
      transcripts to accumulate. We conclude that selection of, but not necessarily
      cleavage at the polyadenylation site precedes excision of the 3'-terminal intron
      in vivo; although coupling exists during selection of the sites to be used for
      polyadenylation and excision of the 3'-terminal intron, the actual order of the
      subsequent enzymatic reactions is probably simply a reflection of their relative
      kinetics.

PMID- 8255784
TI  - MUST, a computer package of Management Utilities for Sequences and Trees.
AB  - The MUST package is a phylogenetically oriented set of programs for data
      management and display, allowing one to handle both raw data (sequences) and
      results (trees, number of steps, bootstrap proportions). It is complementary to
      the main available software for phylogenetic analysis (PHYLIP, PAUP, HENNING86,
      CLUSTAL) with which it is fully compatible. The first part of MUST consists of
      the acquisition of new sequences, their storage, modification, and checking of
      sequence integrity in files of aligned sequences. In order to improve alignment,
      an editor function for aligned sequences offers numerous options, such as
      selection of subsets of sequences, display of consensus sequences, and search for
      similarities over small sequence fragments. For phylogenetic reconstruction, the
      choice of species and portions of sequences to be analyzed is easy and very
      rapid, permitting fast testing of numerous combinations of sequences and taxa.
      The resulting files can be formatted for most programs of tree construction. An
      interactive tree-display program recovers the output of all these programs.
      Finally, various modules allow an in-depth analysis of results, such as
      comparison of distance matrices, variation of bootstrap proportions with respect
      to various parameters or comparison of the number of steps per position. All
      presently available complete sequences of 28S rRNA are furnished aligned in the
      package. MUST therefore allows the management of all the operations required for
      phylogenetic reconstructions.

PMID- 8255785
TI  - Duplicated region of sequence similarity to the human XRCC1 DNA repair gene in
      the Schizosaccharomyces pombe rad4/cut5 gene.

PMID- 8255786
TI  - YAC subclone contig assembly by serial interspersed repetitive sequence (IRS)-PCR
      product hybridizations.

PMID- 8255787
TI  - ICI 164,384: a control for investigating estrogen responsive genes.

PMID- 8255788
TI  - Isolation of genomic DNAs from plants, fungi and bacteria using benzyl chloride.

PMID- 8255789
TI  - Formation of protein conjugates of phosphorothioate nucleoside diphosphate beta
      S.

PMID- 8255790
TI  - PCR amplification of highly GC-rich DNA template after denaturation by NaOH.

PMID- 8255792
TI  - Aortic diastolic pressure decay in congenital arteriovenous malformations.
AB  - We describe three infants with large congenital arteriovenous malformations, two
      intracranial and one intrathoracic, who have high output congestive heart failure
      but normal pulse pressures. The theoretical basis of these pulse pressure
      findings in contrast to those in infants with shunting secondary to the patent
      ductus arteriosus is presented.

PMID- 8255791
TI  - Atrial tachycardia in infants and children: electrocardiographic classification
      and its significance.
AB  - An electrocardiographic classification of atrial tachycardia and its significance
      in children has not been reported. We reviewed the clinical histories and 12-lead
      surface electro-cardiograms (ECG) of 21 children with atrial tachycardia. Atrial
      rate and P-wave axis were determined for each patient. Some patients had features
      of typical atrial flutter (AF). Tachycardia was classified by atrial rate <
      340/min or atrial rate > 340/min. Children with atrial tachycardia rate > 340/min
      consistently responded to conservative treatment (digoxin and/or cardioversion)
      without recurrences (p < 0.05 and p > 0.025); whereas in children with atrial
      rate < 340/min, only one case responded to conservative therapy. P-wave axis had
      no prognostic significance for either group. Additionally, high atrial rate (>
      340/min) during tachycardia was noted in early infancy, compared to older
      children and adults, and probably represents the function of age. Classification
      of atrial tachycardia by rate is clinically useful for planning therapy and
      predicting response in children.

PMID- 8255793
TI  - Congenital coronary artery fistulae: a review of 18 cases with special emphasis
      on spontaneous closure.
AB  - Between 1972 and 1990, 18 patients (median age 3 years, range 0.1-14 years) with
      coronary artery fistulae (CAF) were seen at this institution. Of the 16 patients
      without associated heart defects, two patients presented with congestive heart
      failure and the remaining 14 were asymptomatic. Fifteen patients had normal
      origin of two coronary arteries. Two patients had atresia of the proximal right
      coronary artery and, in one patient, the right coronary artery originated from
      the left main coronary artery. The QP/QS ranged between 1.0 and 2.8, with a mean
      of 1.4. Fifteen patients underwent operative closure without any deaths. One
      patient is being followed medically at present. Two patients showed spontaneous
      clinical improvement of CAF (complete closure in one and near complete in the
      other) and remained asymptomatic during a decade of follow-up. Review of the
      literature suggests operative closure of symptomatic and asymptomatic small CAF
      during childhood. However, the natural history of minute CAF remains unclear. In
      addition, symptoms from CAF may spontaneously improve with time.

PMID- 8255795
TI  - Parental knowledge of bacterial endocarditis prophylaxis.
AB  - The aim of this study was to determine parental knowledge of bacterial
      endocarditis prophylaxis (BEP). Parents of 135 patients attending a pediatric
      cardiology clinic in a university center were mailed an eight-question survey
      pertaining to their knowledge of their child's cardiac disease, medications, and
      BEP. The patients' cardiac lesions and current medications were verified by a
      review of clinic and echocardiographic records. Each patient's need for BEP was
      determined according to American Heart Association (AHA) recommendations. Eighty
      four (62%) parents returned complete surveys. The patients' mean age was 5 years
      with a range of 9 weeks to 19 years. Eighty-two (98%) respondents were high
      school graduates. Fifty-two (62%) respondents correctly defined endocarditis.
      Eighty-two (98%) parents knew the correct name of their child's cardiac condition
      and 27/32 (84%) knew the names of their child's current medications. Only 36/64
      (56%) parents of at-risk children knew measures to prevent endocarditis. While
      most parents know the name of their child's heart lesion and current medications,
      parental knowledge of endocarditis and BEP was limited. Intensified education and
      awareness programs are needed in order to prevent potential major morbidity and
      mortality for pediatric patients with heart disease.

PMID- 8255794
TI  - Clinical significance of late potential in patients with Duchenne muscular
      dystrophy.
AB  - The relationship between late ventricular potentials (LP) and myocardial ischemic
      changes or ventricular arrhythmias was investigated in patients with Duchenne
      muscular dystrophy (DMD). Twenty-six DMD patients aged 10-33 years (mean 18.2
      years) and 27 age-matched healthy volunteers were studied. Ventricular
      arrhythmias were detected by 24-h Holter ECGs and LPs were determined using
      signal-averaged ECGs. In DMD patients filtered QRS duration, late duration, and
      low-amplitude signal under 40 microV were significantly prolonged compared with
      those of the controls. The root mean square voltage of the f-QRS complex in the
      last 40 ms was lower in DMD patients than in the controls. None of the control
      subjects had LP. However, LP was detected in 8 (31%) of the 26 DMD patients. The
      patients with LP had more frequent ST-T depression and ventricular arrhythmias
      than the patients without LP. LP had 60% sensitivity and 87% specificity for
      documented ventricular arrhythmias. It is concluded that LP in DMD patients
      indicates the presence of substrate for ventricular arrhythmias associated with
      local myocardial fibrosis, and is useful in identifying those at high risk for
      malignant ventricular arrhythmias.

PMID- 8255796
TI  - Atypical presentation of Kawasaki disease in an infant.
AB  - A 7-month-old male infant with clinical symptoms of severe toxic shock syndrome
      died on day 9 of illness. At autopsy, demonstration of coronary vasculitis
      together with thrombosis of the left coronary artery revealed the true diagnosis
      of atypical Kawasaki disease. The marked similarity in many clinical features
      makes the distinction between these two diseases difficult when atypical clinical
      presentation of Kawasaki disease is present.

PMID- 8255797
TI  - Captopril-induced bone marrow suppression in two cardiac patients with trisomy
      21.
AB  - Neutropenia is an infrequent complication following administration of the
      angiotensin-converting enzyme (ACE) inhibitor, captopril. Most reports have been
      in adult patients, with rare reports in the pediatric population. We report two
      cases of neutropenia following captopril use in cardiac patients with trisomy 21.
      As this was not seen in patients without Down's syndrome, we postulate that
      patients with trisomy 21 have bone marrow which is "at risk" for suppression,
      and, thus warrant close evaluation while on such medications.

PMID- 8255798
TI  - Pulmonary blood supply by a branch from the distal ascending aorta in pulmonary
      atresia with ventricular septal defect: differential diagnosis of fifth aortic
      arch.
AB  - A patient with pulmonary atresia and a ventricular septal defect is described in
      whom an arterial branch from the distal ascending aorta supplied segments of both
      lungs. The branch is considered to represent a persistent fifth aortic arch. The
      possible morphogenesis and differential diagnosis of a communication between the
      ascending aorta and the pulmonary artery in pulmonary atresia with ventricular
      septal defect are discussed.

PMID- 8255799
TI  - Scimitar syndrome associated with partial anomalous pulmonary venous connection
      at the supracardiac, cardiac, and infracardiac levels.
AB  - A 1-year-old female child was diagnosed to have scimitar syndrome associated with
      partial anomalous pulmonary venous connection of the right lung at the superior
      vena cava-right atrial junction, right atrium, and inferior vena cava. To our
      knowledge, this pattern of pulmonary venous connection has not been previously
      described in this syndrome.

PMID- 8255800
TI  - Superoinferior ventricles with criss-cross atrioventricular connections and
      intact ventricular septum.
AB  - We report a 6-year-old girl with superoinferior ventricles, criss-cross
      atrioventricular (AV) relationships with solitus atria, a D-loop, L-transposition
      of the great arteries, subpulmonary stenosis, but without a ventricular septal
      defect (VSD). The diagnosis was made by echocardiographic examination and was
      strengthened by cardiac catheterization and angiocardiography. Balloon atrial
      septostomy in the neonatal period and a modified Blalock-Taussig shunt at the age
      of 16 months were performed to alleviate hypoxia. Following the shunt operation,
      the clinical condition of the patient deteriorated with progressive cardiac
      enlargement, congestive heart failure, and tricuspid regurgitation. We assume
      that the absence of a VSD contributed to this deterioration. Subsequent
      improvement was obtained with balloon enlargement of the atrial septal defect and
      a bidirectional Glenn anastomosis.

PMID- 8255801
TI  - Definition of inseparably fused ventricular myocardium in thoracopagus: fetal
      echocardiographic utility and pathologic refinement.
AB  - Correlative echocardiographic and pathological findings in a thoracopagus with
      conjoined hearts are reported. One twin had tricuspid atresia with discordant
      atrioventricular connections and concordant ventriculoarterial connections. The
      morphologic right ventricle was hypoplastic and there was a large muscular
      ventricular septal defect. The other twin had hypoplasia of the mitral valve
      anulus and left ventricle with double-outlet right ventricle and pulmonary valve
      atresia. The tricuspid valve was severely insufficient in part because of a large
      orifice and redundant, elongated leaflets with abnormal chordal attachments. The
      left ventricles of these two twins shared a perforated common "free wall" with at
      least two large defects allowing mixing of the circulations at that level. Not
      all anatomic details were established conclusively by fetal echocardiography;
      however, sufficient diagnostic information was obtained to support a decision not
      to aggressively resuscitate these twins after elective cesarean delivery at 31
      weeks' gestation.

PMID- 8255802
TI  - "Eight-chamber" view.

PMID- 8255803
TI  - Why do outcomes research?

PMID- 8255804
TI  - Closure of the physis after pinning of slipped capital femoral epiphysis.
AB  - A study was conducted to determine what effect pinning in situ for slipped
      capital femoral epiphysis (SCFE) had on the timing of subsequent closure of the
      growth plate. Eighty-nine patients with a SCFE were reviewed. Twenty-six patients
      with a unilateral SCFE were treated with closed pinning in situ; no manipulative
      reductions were performed. The timing of physeal closure was assessed using
      postoperative radiographs of both pinned and non-pinned sides. The average time
      until physeal closure was 12.0 months for the pinned physis and 22.2 months for
      the non-pinned physis. In two cases, the physes closed simultaneously, and in no
      patient did the non-pinned physis close earlier than the pinned physis. The
      pinned physes closed an average of 10.2 months (range: 0 to 22) earlier than the
      unpinned physes. No difference was noted in the rates of closure with different
      types of internal fixation. This study supports the theory that pinning SCFE in
      situ causes early closure of the physis.

PMID- 8255805
TI  - Intravenous regional anesthesia for outpatient foot and ankle surgery: a
      prospective study.
AB  - A prospective study was undertaken in 39 patients undergoing 48 foot and ankle
      procedures using intravenous regional anesthesia (IVRA). IVRA was administered
      using 35 cc of 0.33% or 0.5% lidocaine. Single tourniquets inflated to 250 mm Hg
      were used at the ankle level. No supplemental analgesia or sedation was used.
      Those requiring supplemental local anesthetic infiltration were defined as IVRA
      failures. Thirty-one of the 39 patients (79.5%) tolerated the procedures with
      little or no discomfort, and 8 (20.5%) required additional local infiltration
      with 1% lidocaine. All 39 patients completed the procedures at the outpatient
      surgical unit without requiring conversion to other forms of anesthesia. Patchy
      non-anesthetic areas were noted in 14 patients (36.8%). In 7 patients, because
      the non-anesthetic areas were excluded from the operative fields, the procedures
      were completed without discomfort. However, in 8 patients where the non
      anesthetic areas were directly involved in the operative fields, supplemental
      local anesthesia was required. Only 1 of the 39 patients complained of tourniquet
      pain. IVRA compared favorably with other methods of regional anesthesia in the
      lower extremity with respect to ease of technique, speed of onset, safety, and
      patient acceptance. However, it appears that it is less reliable than IVRA in the
      upper extremity. The reasons for this difference will require further
      investigation.

PMID- 8255806
TI  - Metastatic carcinoma of the spine with neurologic complications: an autopsy
      review.
AB  - We conducted post-mortem examinations on 12 patients who had documented
      metastatic carcinoma to the spine with attendant neurologic complications. The
      examinations were studied to determine the location of the metastatic lesion in
      relation to the spinal cord. Both gross and microscopic examinations were
      performed, with particular attention to the level of compression. The majority of
      the metastatic tumors involved the vertebral body and pedicles anterior to the
      spinal cord. The findings of this autopsy review support previous surgical
      findings, and re-emphasize the importance of considering tumor location before
      treating compression of the spinal cord secondary to metastatic carcinoma.

PMID- 8255807
TI  - Ankle weight effect on gait: orthotic implications.
AB  - Oxygen consumption during ambulation was measured in 10 normal subjects wearing
      ankle weights of 0.91 kg, 1.82 kg, and 2.73 kg, either on the right ankle or
      bilaterally. Subjects walked at self-selected speeds and oxygen consumption was
      measured over 1-minute intervals during steady-state walking. Oxygen consumption
      per unit distance and oxygen consumption rate demonstrated significant positive
      linear correlations with added weight (P = .001, P = 0.007, respectively).
      Velocity demonstrated a significant decrease when correlated with added weight (P
      = 0.03). Multiple regression analysis was used to relate these measures of oxygen
      consumption rates to velocity, age, and added weight, yielding predictive
      relationships. Based on these results, the weight of orthoses should be minimized
      in order to maximize walking velocity and minimize oxygen consumption per unit
      distance. The advantage of a light-weight, molded plastic ankle-foot orthosis
      (AFO) over heavier AFO designs is demonstrated by this study.

PMID- 8255808
TI  - Neuropathic arthropathy of the shoulder mimicking soft tissue sarcoma.

PMID- 8255809
TI  - Failure of the polyethylene tibial component of a TKR associated with aseptic
      loosening secondary to polyethylene and metallic wear debris.

PMID- 8255810
TI  - Rapidly destructive squamous cell carcinoma as a complication of chronic
      osteomyelitis.

PMID- 8255811
TI  - Traumatic dislocation of the hip in a child: usefulness of MRI.

PMID- 8255812
TI  - Plantar fasciitis.

PMID- 8255813
TI  - Use of a modified Quengel hinge to prevent posterior displacement of the tibia
      during treatment of PCL injury.
AB  - During treatment of posterior cruciate ligament (PCL) injuries, posterior
      displacement of the tibia may occur inside the cast due to the effect of gravity
      on the lower leg. To prevent this problem the authors attempted to apply the
      original Quengel cast, first described by Mommsen in 1922 and perfected by
      Jordan, to correct the flexion contracture of the knee in hemophiliacs. However,
      the authors found that the cast was not effective in preventing the posterior
      displacement of the tibia during management of PCL injuries. They modified the
      design of the original Quengel hinge to obtain a more effective anterior traction
      on the tibia parallel to the knee joint line. Of the 32 patients who used the
      modified Quengel brace, 15 who could be followed had less than a 3 mm difference
      between the injured and uninjured knee 3 months postoperatively.

PMID- 8255814
TI  - Benign giant cell tumor.

PMID- 8255815
TI  - Radiologic case study. Spondylolysis in a 2-year-old girl.

PMID- 8255816
TI  - Guides for record review. Closed head injury. American Board of Pediatrics.

PMID- 8255817
TI  - Role of the general pediatrician in the management of human immunodeficiency
      virus infection in children.

PMID- 8255818
TI  - Depression and suicide in children and adolescents.
AB  - Depression, suicide, and suicidal behavior in the pediatric population are
      serious public health problems. Pediatricians in collaboration with psychiatrists
      and other mental health professionals can make an important contribution to the
      mental health of children and adolescents through the identification, referral,
      and management of depressed and suicidal youth.

PMID- 8255819
TI  - Skull fractures in infancy and childhood.

PMID- 8255820
TI  - Managing patients who have asthma: the pediatrician and the school.

PMID- 8255821
TI  - Foot and leg problems.

PMID- 8255822
TI  - Sexuality in children.

PMID- 8255823
TI  - IgG subclasses: importance in pediatric practice.
AB  - Although many clinical studies provide evidence of a relation between IgG
      subclass deficiency and increased susceptibility to infection, a direct cause-and
      effect relationship clearly does not exist. Each patient must be managed in the
      full context of clinical symptomatology, reliable measurement of IgG subclasses,
      and evaluation of specific antibody production. Future studies may clarify the
      factors that stimulate and regulate the production of IgG subclasses and improve
      our understanding of their role in the health of children.

PMID- 8255824
TI  - Screening for scoliosis.

PMID- 8255825
TI  - When parents become critical observers: caring for the child who has a head
      injury.

PMID- 8255826
TI  - Abdominal pain unrelated to trauma.

PMID- 8255827
TI  - Recurrent abdominal pain during childhood.
AB  - RAP offers a complex and often confusing array of symptoms and diagnostic
      possibilities. This may be due to its unique age of presentation, its inherent
      somatic and cognitive developmental issues, or the physiology of abdominal pain
      itself. A careful examination of the historic and physical findings should
      produce a therapeutic plan that addresses somatic, psychological, and
      environmental aspects of the child. This process will avoid overly simplistic and
      premature misdiagnosis or potentially unnecessary investigations that convey a
      sense of disinterest, haste, and disbelief in the problem. The successful
      management of RAP lies in the recognition that serious underlying disease
      frequently is not present and that time usually is on our side. It is the process
      of continued and thoughtful evaluation and reassurance over time that counts.

PMID- 8255828
TI  - Otitis media.

PMID- 8255829
TI  - Point-counterpoint. Sexual abuse--the yellow flag is still up.

PMID- 8255830
TI  - Who should be offered genetic screening?

PMID- 8255831
TI  - Renal replacement therapy in multiple myeloma and systemic amyloidosis.

PMID- 8255833
TI  - Comparison of clock drawing with Mini Mental State Examination as a screening
      test in elderly acute hospital admissions.
AB  - Clock drawing is a quick, easy to remember test that is well received by
      patients. It is a good screening test for Alzheimer's disease in the outpatient
      setting. We evaluated its usefulness compared with the standard Mini Mental State
      Examination (MMSE) in elderly acute medical and surgical hospital admissions.
      Within 48 hours of admission, 117 patients over 70 years old were administered
      the MMSE and asked to draw a clock. Using the MMSE as the standard, clock drawing
      had a sensitivity of 77% and a specificity of 87%. Patients with discrepant
      scores were then further evaluated. The findings suggest that normal clock
      drawing ability reasonably excludes cognitive impairment or other causes of an
      abnormal MMSE in elderly acute medical and surgical hospital admissions, where
      cognitive impairment is common and frequently missed.

PMID- 8255834
TI  - Restless legs syndrome in the elderly.
AB  - The prevalence and significance of restless legs syndrome was assessed in 307
      patients presenting to an acute-care geriatric medical service. Fifteen patients
      (5%) had restless legs syndrome; 13 (87%) of these patients had insomnia and 10
      (67%) reported troublesome or frequent leg symptoms. Of 147 patients with current
      insomnia, iron deficiency (serum ferritin < 18 ng/ml) was present in 4/13 (31%)
      patients with restless legs and 8/134 (6%) patients without restless legs (P <
      0.025). Improvement in symptoms of restless legs was noted with iron repletion.
      These findings suggest that restless legs syndrome is relatively common in the
      elderly and causes significant discomfort and sleep disturbance. Iron deficiency
      is a common and treatable cause.

PMID- 8255835
TI  - Microalbuminuria and coronary heart disease in non-diabetics.
AB  - Microalbuminuria (or urinary albumin excretion rates (AER) above normal limits)
      is associated with coronary heart disease (CHD) particularly in diabetics. To
      determine the sensitivity and specificity of AER for CHD in a non-diabetic
      population we prospectively studied 115 consecutive patients undergoing coronary
      angiography and 66 undergoing exercise electrocardiography (ECG). There was no
      relationship between AER and the severity of CHD determined by angiography
      (Gensini-scored). While microalbuminuria (AER > 20 micrograms/minute) was 91%
      specific it had low sensitivity (12%). Microalbuminuria is not a sensitive
      indicator of CHD in a non-diabetic population.

PMID- 8255832
TI  - Triglycerides and disease.

PMID- 8255836
TI  - Serum soluble interleukin 2 receptor levels in anti-neutrophil cytoplasmic
      autoantibodies--positive systemic vasculitis.
AB  - Systemic vasculitis is characterized by the presence of autoantibodies to
      neutrophil cytoplasmic antigens (ANCA). The role of T-lymphocytes in systemic
      vasculitis remains uncertain. In the present study, we attempted to explore the
      role of T-lymphocytes in systemic vasculitis by measuring the serum soluble
      interleukin 2 receptor (sIL2R) levels in seven vasculitic patients and comparing
      the sequential measurements with the titres of ANCA which satisfactorily reflect
      the disease activity. The serum levels of both ANCA and sIL2R were elevated at
      clinical presentation. Contrary to ANCA, the serum sIL2R remained elevated in
      most patients despite clinical remission following immunosuppressive therapy.
      These findings suggest that T-lymphocytes may be activated in the acute phase of
      the disease. The finding of elevated serum sIL2R levels in most patients during
      clinical remission indicates that it is not a good measure of the disease
      activity and tends to argue against the role of T-lymphocytes as a major effector
      mediating inflammatory injuries in systemic vasculitis.

PMID- 8255837
TI  - Gastro-duodenal injury associated with intake of 100-325 mg aspirin daily.
AB  - During the year 1991, 43 patients with upper gastrointestinal bleeding and one
      with severe epigastric pain associated with intake of non-steroidal anti
      inflammatory drugs were admitted for emergency endoscopy to our unit. Fourteen
      patients (33%) had been treated with 100-325 mg aspirin daily, 11 of them for at
      least one year. The mean age of this group was 71. Only two patients had a
      previous history of peptic ulcer. Five patients used anticoagulants or
      antiplatelet drugs concomitantly with aspirin. The endoscopic diagnosis of the
      sources of bleeding was erosive gastritis in eight patients, gastric ulcer in
      four, duodenal ulcer in five and oesophageal ulcer in one. Our results support
      findings by other groups, showing that doses of aspirin as low as 75 mg daily
      should be used in the management of elderly patients with thrombo-embolic
      disease.

PMID- 8255838
TI  - Liver/spleen scintigraphy for diagnosis of splenic infarction in cirrhotic
      patients.
AB  - Splenic infarction is rare in cirrhotic patients. The diagnosis of the condition
      is based on clinical findings and splenic imaging. In recent years,
      ultrasonography and computed tomographic scan have gained popularity over the
      more classical scintigraphy as the preferred investigations for the diagnosis of
      splenic infarction. We report three cases of splenic infarction in patients with
      cirrhosis and portal hypertension. Computed tomographic scan, angiography and
      ultrasonography failed to identify the lesions and the diagnoses were finally
      made with the aid of liver--spleen scintigraphy. We suggest that scintigraphy is
      the investigation of choice if splenic infarction is suspected in patients with
      congestive splenomegaly secondary to liver cirrhosis.

PMID- 8255839
TI  - The singularity of pluralism.

PMID- 8255840
TI  - Cervical spondylotic myelopathy with occult foramen magnum meningioma--a case for
      MRI?
AB  - A fatal case of occult foramen magnum meningioma is described which presented
      with features of cervical myelopathy confirmed by cervical myelogram. Surgical
      decompression led to initial improvement followed by progressive deterioration
      and death. Postmortem examination revealed a 4 cm diameter foramen magnum
      meningioma. The dangers of using only standard radiographic investigations of the
      cervical cord are discussed.

PMID- 8255841
TI  - Rigors in tuberculosis.
AB  - Rigors are not a recognized characteristic of miliary tuberculosis. We report two
      patients presenting with persistent rigors, thought to be suggestive of acute
      pyogenic infection, who were subsequently found to have miliary tuberculosis. In
      both cases, there was significant diagnostic delay. Miliary tuberculosis should
      therefore be included in the differential diagnosis of any patient presenting
      with unexplained rigors.

PMID- 8255842
TI  - Bowel obstruction.

PMID- 8255843
TI  - Introducing the student and trainee to biomedical experimentation--a selective
      annotated bibliography.

PMID- 8255844
TI  - Gram-negative meningitis and chronic constipation: an unusual presentation of
      caudal regression syndrome.
AB  - Congenital malformations may present as meningitis caused by enteric organisms,
      but this is extremely rare and occurs almost exclusively in the paediatric
      population. We report an unusual case of a young man with chronic constipation
      presenting with spontaneous Gram-negative meningitis due to an underlying
      congenital spinal malformation known as the caudal regression syndrome.

PMID- 8255845
TI  - Effects of octreotide on circulating islet B cell products in endogenous
      hyperinsulinism.
AB  - The role of somatostatin analogues in the medical management of insulinomas is
      unclear. We describe an elderly patient with clinical and biochemical features of
      endogenous hyperinsulinism attributable to a benign islet B cell disorder whose
      incapacitating neuroglycopaenic symptoms responded dramatically to octreotide 50
      micrograms subcutaneously at 2200 h each night. Octreotide suppressed
      inappropriate plasma concentrations of insulin thereby preventing fasting
      hypoglycaemia. Fasting concentrations of proinsulin, and 32-33 split proinsulin,
      as determined by two-site monoclonal antibody-based immunoradiometric assays,
      were also suppressed by octreotide.

PMID- 8255846
TI  - Cardiac arrest: a rare complication of pallid syncope?
AB  - Cardiac arrest is rare in children. Breath-holding, on the other hand, is fairly
      common. We report a case in which one complicated the other with serious
      consequences. A review of the literature on the subject was undertaken.

PMID- 8255847
TI  - Spontaneous biloma in an elderly patient.
AB  - A previously well 84 year old man without prior history of abdominal trauma,
      instrumentation or surgery presented with localized biliary peritonitis (biloma).
      An associated bile duct stone was detected by abdominal ultrasound and endoscopic
      retrograde cholangiopancreatography and was successfully treated with systemic
      antibiotics and percutaneous and endoscopic stenting. The case is unusual in that
      the presentation was spontaneous.

PMID- 8255848
TI  - Osteomyelitis of symphysis pubis following renal transplantation.
AB  - We describe what we believe is the first reported case of osteomyelitis of the
      symphysis pubis following renal transplantation. Computed tomographic and
      magnetic resonance imaging scans were useful in establishing the diagnosis.

PMID- 8255849
TI  - Spontaneous rupture of the spleen in association with idiopathic
      thrombocytopaenic purpura.
AB  - Spontaneous rupture of the spleen is rare and has not been previously reported in
      association with idiopathic thrombocytopaenic purpura. Its rarity makes
      familiarity with its presentation difficult and may result in a potentially fatal
      delay in diagnosis and treatment.

PMID- 8255850
TI  - Spinal ganglioneuroblastoma--complete response to chemotherapy alone.
AB  - Ganglioneuroblastoma in the spinal region is rare, the treatment of choice being
      surgical excision. We present a 21 year old male who was diagnosed to have this
      condition in the dorsolumbar spinal region. The tumour was extending
      intraspinally and was unresectable. Combination chemotherapy with Adriamycin
      (doxorubicin hydrochloride), vincristine, cyclophosphamide, etoposide, ifosfamide
      and cisplatin resulted in histologically proven complete remission. No
      radiotherapy or curative resection was done. The patient is alive without
      evidence of disease 24 months later. Never before has chemotherapy been
      successfully used as the sole modality of treatment in this condition. Our report
      raises important questions about the management of this rare condition,
      particularly in a situation of unresectability.

PMID- 8255851
TI  - Is clubbing a feature of the anti-phospholipid antibody syndrome?
AB  - A patient with the anti-phospholipid antibody syndrome and digital clubbing is
      described. No recognized cause for the clubbing was found. It is suggested that
      platelet aggregation and microthrombi formation as a result of anti-phospholipid
      antibody may be involved in the pathogenesis of the digital clubbing. This may be
      a new feature of the anti-phospholipid antibody.

PMID- 8255852
TI  - The development of spontaneous colo-umbilical fistula.
AB  - A patient with colo-umbilical fistula is reported. This presentation is unique
      because it documents the development of a fistula from a colonic diverticulum.
      Sigmoid colectomy was undertaken successfully.

PMID- 8255853
TI  - A patient with recurrent hypothermia associated with thrombocytopenia.

PMID- 8255854
TI  - Hypertension and hypoparathyroidism--narrowed therapeutic safety with nifedipine.

PMID- 8255855
TI  - Lymphopaenia in elderly in-patients.

PMID- 8255856
TI  - Hyperplastic gingivitis: an oral manifestation of Wegener's granulomatosis.

PMID- 8255857
TI  - Laser treatment of endometriosis.

PMID- 8255858
TI  - Postviral fatigue syndrome.

PMID- 8255860
TI  - Urinary incontinence.

PMID- 8255859
TI  - Non-specific urethritis.

PMID- 8255861
TI  - Calcium-channel antagonists.

PMID- 8255862
TI  - Women and HIV infection.

PMID- 8255863
TI  - Starting out as a trainee.

PMID- 8255864
TI  - The trainee's view.

PMID- 8255866
TI  - A strategy for success.

PMID- 8255865
TI  - Talking about sex.

PMID- 8255867
TI  - Behavioural problems.

PMID- 8255868
TI  - The febrile child.

PMID- 8255869
TI  - Caring for handicapped children.

PMID- 8255870
TI  - The vomiting child.

PMID- 8255871
TI  - Prevention of malaria.

PMID- 8255872
TI  - Inflammatory cervical smears.

PMID- 8255873
TI  - Primary health care teams.

PMID- 8255874
TI  - Erectile impotence.

PMID- 8255875
TI  - Passing the MCQ.

PMID- 8255876
TI  - Viral infections.

PMID- 8255877
TI  - Sore throat.

PMID- 8255878
TI  - Infection and pregnancy.

PMID- 8255879
TI  - Antibiotic policies.

PMID- 8255880
TI  - Penetrating wounds.

PMID- 8255881
TI  - New drugs for asthma.

PMID- 8255882
TI  - Pathology of acute and chronic pancreatitis.

PMID- 8255883
TI  - Evaluation of the clinical usefulness of APACHE II and SAPS systems in the
      initial prognostic classification of acute pancreatitis: a multicenter study.
AB  - The clinical usefulness of the APACHE II and SAPS systems in the early prognostic
      classification of patients with acute pancreatitis has been evaluated in a
      prospective multicenter study. We aimed to identify early those patients with
      acute pancreatitis who should be monitored closely to expedite the detection and
      treatment of complications. One hundred eighty-two patients with acute
      pancreatitis were included; 28 were classified as severe, having developed at
      least one major complication of the disease. The scores obtained through the
      APACHE II and SAPS systems in these severe cases were significantly higher than
      the scores in the mild cases of acute pancreatitis (p < 0.001). The sensitivity
      of these systems in the prognostic classification of acute pancreatitis was 70.4%
      for APACHE II and 66.7% for SAPS, and the specificity was 79.1% for both. When
      applying APACHE II and SAPS systems in the early phase of acute pancreatitis, the
      possibility of misdiagnosing the severity exists, thus limiting the application
      of these systems in the initial assessment of prognostic classification. In
      conclusion, APACHE II and SAPS systems are of limited clinical utility in the
      early prognostic evaluation of acute pancreatitis because of their low positive
      predictive value.

PMID- 8255884
TI  - Arterial complications of pancreatitis: diagnostic and therapeutic role of
      radiology.
AB  - Hemorrhage from pseudoaneurysm complicating pancreatitis is an infrequent but
      very severe condition. In most cases, acute, massive gastrointestinal bleeding is
      typical at onset, and prognosis of these cases is usually poor. Nine cases of
      arterial lesions secondary to pancreatic inflammation are presented, eight
      related to chronic pancreatitis and one to acute postoperative pancreatitis. Five
      patients were evaluated during emergency episodes because of acutely
      gastrointestinal bleeding (four cases), and pseudocyst acute bleeding (one case).
      Four patients were selectively evaluated: three had a history of self-limiting
      gastrointestinal hemorrhage, whereas one had experienced no episodes of
      gastrointestinal hemorrhage. Angiography was performed in all cases and was
      always diagnostic, even in the two cases of very small pseudoaneurysms.
      Transcatheter arterial blockade was attempted in five patients and failed to
      control the hemorrhage in one acutely bleeding patient because of irreversible
      shock. Two cases of pancreatic hemorrhage not related to a pseudocyst were
      effectively and permanently treated by embolization. A case of a pseudoaneurysm
      associated with a pseudocyst required surgery in addition to embolization for a
      definite treatment. Nevertheless, when a pseudoaneurysm or a pseudocyst
      hemorrhages acutely, transcatheter arterial blockade can control the hemorrhage
      and improve the hemodynamic status of the patient before surgery.

PMID- 8255885
TI  - Expression and distribution of VLA receptors in the pancreas: an
      immunohistochemical study.
AB  - Very late activation (VLA) receptors mediate cell adhesion to extracellular
      matrix, mainly by acting as adhesion receptors to fibronectin, collagen, and
      laminin as well as to other cells. These interactions not only regulate normal
      cell-extracellular matrix contact, but also are thought to be involved in
      metastasis and invasive tumor growth. Using immunohistochemistry [the alkaline
      phosphatase-anti-alkaline phosphatase (APAAP) technique] we compared the
      expression and distribution of VLA receptors in normal pancreatic tissue, chronic
      pancreatitis, and ductal pancreatic adenocarcinoma. Immunohistochemically, VLA
      alpha 2 and VLA alpha 6 were moderately to strongly expressed on the basal
      surface of ductal and acinar cells in normal pancreatic tissue, whereas
      centroacinar cells predominantly expressed VLA alpha 3 and VLA alpha 5.
      Similarly, pancreatic carcinoma showed an intensive staining for VLA alpha 2 and
      VLA alpha 6 with a diffuse distribution on the cell surface. Expression of VLA
      alpha 3 and VLA alpha 5 in pancreatic carcinoma was heterogeneous, ranging from
      moderate to weak and lost in about 50% of the cells. As our results suggest, cell
      basement membrane interaction in ductal and acinar pancreatic cells is primarily
      mediated through VLA alpha 2 and VLA alpha 6, whereas VLA alpha 3 and VLA alpha 5
      are the major VLA receptors on centroacinar cells. In pancreatic carcinoma a loss
      (VLA alpha 5) or redistribution (VLA alpha 2, VLA alpha 6) of VLAs was observed.
      This redistribution of VLA alpha 2 and VLA alpha 6 may reflect a loss of spatial
      arrangement of tumor cells and their ability to randomly interact with
      extracellular matrix structures during invasion and metastasis.

PMID- 8255886
TI  - Chronic hyperglycemia and the human fetal beta cell.
AB  - It is well known that the ability of the immature rodent fetal beta cell to
      release insulin in response to a glucose challenge can be enhanced by chronic
      exposure to a high concentration of glucose in vitro. It might be thought that
      the human fetal beta cell would mature similarly in vitro, because neonates born
      of diabetic mothers release insulin in a more mature manner than normal infants.
      Using an organ culture of human fetal pancreatic explants, we have examined this
      possibility by exposing the tissue to 0-30 mM glucose. Six weeks of exposure of
      pancreatic explants to as high a concentration of glucose as 30 mM did not cause
      significant enhancement of the insulinogenic response to an acute challenge with
      20 mM glucose. In contrast, chronic insulin release was enhanced, although
      culture medium containing 2.8 mM glucose was equally as efficacious as that with
      30 mM glucose. Just as with insulin, proinsulin levels in the culture media
      containing no glucose also were suppressed. Degranulation of the beta cell
      exposed to high concentrations of glucose did not occur, the insulin content of
      the explants at the end of culture being enhanced in those maintained in 5.6-30
      mM but not 2.8 mM glucose. Desensitization to the acute stimulatory effect of 10
      mM theophylline did not eventuate, even in explants exposed to 30 mM glucose. In
      contrast to the human explants, rat fetal pancreatic explants did mature when
      exposed to 11.2 mM glucose for 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255887
TI  - Effects of pulsatile glucose stimuli on long-term insulin secretory patterns in
      islets of Langerhans microdissected from Syrian hamsters.
AB  - The long-term effects of continuous and pulsatile glucose stimulation of islets
      of Langerhans microdissected from Syrian hamsters were examined. In the presence
      of a continuous glucose stimulus insulin secretion peaked during the first 3 h of
      stimulation followed by a decrease. In the presence of 11.2 mM glucose a second
      smaller peak of insulin secretion was observed 14-16 h after the perifusion
      started. Irrespective of the glucose concentration, insulin secretion then
      steadily decreased and reached very low levels by the end of the 48-h perifusion.
      However, glucose stimulus provided in a pulsatile manner appeared to reduce this
      rate of decrease in insulin secretion. Thus, after 48 h, islets exposed to the
      pulsatile glucose stimulus showed greater insulin responsiveness to glucose than
      those exposed to a constant glucose stimulus.

PMID- 8255888
TI  - Clinically based classification system for acute pancreatitis.

PMID- 8255889
TI  - Pancreatic duct permeability and pancreatitis.

PMID- 8255890
TI  - Angiographic embolization therapy of pseudoaneurysm: comment on "arterial
      complications of pancreatitis".

PMID- 8255891
TI  - Late pancreatic metastasis from renal cell carcinoma.

PMID- 8255892
TI  - Choledochal cyst with a rare type of anomalous pancreaticobiliary ductal union.

PMID- 8255893
TI  - [The attitudes and behaviors of nursing students towards smoking].

PMID- 8255894
TI  - [Nursing care and the quality of the services].

PMID- 8255895
TI  - [The nursing profession in relation to efficiency and costs].

PMID- 8255896
TI  - [Quality, costs and nursing care].

PMID- 8255897
TI  - [Human experimentation: the ethical implications. The Italian Red Cross and the
      Edoardo e Virginia Agnelli School for Professional Nurses, Rome].

PMID- 8255898
TI  - [The updating of personnel: from the scheduling to the conducting of courses].

PMID- 8255899
TI  - Bicuculline infused into the hamster ventral tegmentum inhibits, while sodium
      valproate facilitates, sexual receptivity.
AB  - Progesterone's (P) actions on both the ventral medial nucleus of the hypothalamus
      (VMH) and the ventral tegmental area (VTA) are essential for sexual receptivity
      in female hamsters. Evidence suggests that progesterone's actions in the hamster
      VMH may be genomic while those in the VTA may be mediated nongenomically, via
      GABAA. Ovariectomized female hamsters were bilaterally implanted with cannulae
      aimed toward the VTA. One week after surgery, animals were SC injected with 10
      micrograms estradiol benzoate (EB) and 40 h later with 200 or 500 micrograms P.
      At hour 43.5, 50 ng bicuculline, a GABAA antagonist, was infused into each
      available cannula. Control animals received 0.5 microliter sterile saline
      vehicle, or no infusion. At hour 44, animals were tested for sexual receptivity
      in an observation arena with a sexually experienced male. Histology revealed that
      only animals with bicuculline infused into the VTA had reduced lordosis durations
      compared to controls. Other animals, primed with EB and 200 micrograms
      progesterone, showed a facilitation of sexual receptivity after infusion into the
      VTA of 50 micrograms sodium valproate, a GABAA transaminase inhibitor. These
      results suggest that GABAA plays a necessary role in the mechanism of
      progesterone's actions on sexual receptivity in hamster VTA.

PMID- 8255900
TI  - Neuroendocrine and neurochemical responses to novelty stress in young and old
      male F344 rats: effects of d-fenfluramine treatment.
AB  - To understand some of the mechanisms underlying the neuroendocrine and
      neurochemical changes associated with aging, we administered the serotonin [5
      hydroxytryptamine (5-HT)] releaser and reuptake inhibitor d-fenfluramine (d-FEN;
      0.0, 0.2, or 0.6 mg/kg/day, p.o) for 30-38 days to young (4 months) and old (22
      months) F344 male rats. Rats were stressed by placement into a novel open field
      (OF) for 20 min before sacrifice. Control animals were sacrificed immediately
      upon removal from their home cage (HC). Old rats exhibited less (p < 0.05)
      exploratory behavior than young rats, which was not altered by treatment with d
      FEN. Old HC rats also had higher (p < 0.05) basal plasma levels of
      adrenocorticotropic hormone (ACTH) and prolactin (PRL) than young HC rats. Old OF
      rats showed higher (p < 0.05) levels of ACTH and corticosterone (CORT) than young
      OF animals. A stress-induced increase in PRL secretion was not observed in old
      rats. Subchronic low-dose d-FEN normalized the enhanced ACTH and CORT responses
      of old animals to novelty. In addition to these endocrine changes, stress-induced
      increases in medial frontal cortex (MFC) dopamine (DA) and norepinephrine (NE)
      turnover also were observed. The increase in NE turnover was greater (p < 0.01)
      in old than in young rats. d-FEN treatment blocked the stress-induced increase in
      MFC NE but not MFC DA turnover in both young and old rats. These data support a
      role for 5-HT and/or NE in some age-related neuroendocrine perturbations and
      suggest that increased 5-HT neurotransmission can normalize the hyperactivation
      of the hypothalamo-pituitary-adrenal axis of old male rats.

PMID- 8255901
TI  - Effect of naloxone on the habituation of novelty-induced hypoalgesia: the
      collateral inhibition hypothesis revisited.
AB  - Repeated daily administration of the opiate receptor antagonist naloxone prior to
      hotplate tests provokes longer paw-lick latencies by attenuating the habituation
      of novelty-induced hypoalgesia. This hypoalgesia has been found to persist when
      pain tests are subsequently conducted following saline administration. The
      present experiments were conducted to determine whether the substrates mediating
      the hypoalgesia observed during naloxone and saline tests are similar or
      distinct. Neither the hypoalgesia observed during naloxone nor saline tests were
      affected by the induction of tolerance to the hypoalgesic effect of morphine,
      suggesting that both effects are mediated by nonopioid antinociceptive
      mechanisms. Previous work from our laboratory demonstrated that the hypoalgesia
      observed during naloxone tests is inhibited by clonidine, enhanced by yohimbine,
      and unaffected by prazosin and phentolamine. In the present article, we report a
      similar pattern of results for the hypoalgesia observed during saline tests. It
      is concluded that the substrates mediating both effects are similar. The results
      are discussed in relation to the possibility that an opioid substrate involved in
      habituative learning may be inhibitory on a nonopioid antinociceptive substrate.

PMID- 8255902
TI  - Amperozide, a 5-HT2 antagonist, attenuates craving for cocaine by rats.
AB  - Amperozide, a novel 5-HT2 receptor antagonist with little affinity for the
      dopamine receptor, suppresses the intake of alcohol in rats without affecting
      food intake or inducing other side effects. Because of these actions, amperozide
      was examined for its efficacy on the oral preference by the rat for a solution of
      cocaine. In this study, rats were selected for their voluntary consumption of at
      least 10 mg/kg of cocaine per day in a two-choice paradigm. A solution of 0.02%
      to 0.06% cocaine plus 0.03% saccharin in water was offered to each animal
      simultaneously with a solution of only 0.03% saccharin in water. The consumption
      of food and both fluids, as well as body weight, was recorded daily for three
      successive periods: 4 days of pretreatment baseline; 3 days during injections of
      either amperozide or the saline vehicle solution; and 4 days postinjections.
      Amperozide was administered SC twice daily in a dose of 0.5, 1.0, or 2.5 mg/kg.
      The volitional intake of cocaine was significantly reduced not only during the 3
      day period of injections of amperozide but also during the 4-day posttreatment
      period. Amperozide exerted little or no effect on the intake of food or on body
      weight. Radioligand binding experiments confirmed that amperozide has at least a
      twentyfold greater affinity for 5-HT2 receptors in the frontal cortex of the rat,
      as compared to striatal DA1 and DA2 receptors, with the proportion value similar
      to that of the 5-HT2 receptor antagonist, ritanserin.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8255903
TI  - 5-HT1A-mediated lower lip retraction: effects of 5-HT1A agonists and antagonists.
AB  - This study investigated the production of lower lip retraction (LLR) in the rat
      by the 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)
      tetralin (8-OH-DPAT) and the effect of the putative 5-HT1A antagonists pindolol
      and (1-(2-methoxy-phenyl)-4-[4-(2-phthalimido)-butyl]-piperazine (NAN190). 8-OH
      DPAT (0.125-1.0 mg/kg, IP) caused a dose-related increase in LLR. Pindolol (10-40
      mg/kg, IP) and NAN190 (2.5-10 mg/kg, IP) produced a dose-related block of 8-OH
      DPAT-induced LLR. Pindolol (10-40 mg/kg, IP) when administered alone was also
      found to cause LLR, suggesting that pindolol behaves as a partial agonist in this
      model. This was not the case with NAN190 (2.5-10 mg/kg, IP), which failed to
      produce LLR; however, NAN190 (2.5-10 mg/kg, IP) produced a dose-related block of
      the pindolol-induced LLR. These results clearly demonstrate that the LLR model
      can be used to detect 5-HT1A agonists, partial agonists, and antagonists.

PMID- 8255904
TI  - Naloxone-induced analgesia: involvement of kappa-opiate receptors.
AB  - Rats treated with an acute high dose (30 mg/kg) or 4 days with a lower dose (5
      mg/kg) of naloxone or naltrexone show an analgesic response at the hot-plate
      test. This paradoxical analgesic effect of the two mu-opiate receptor antagonists
      is blocked by the kappa opiate receptor antagonist MR 1452, and is modulated by
      the kappa opiate receptor agonist U 50-488. Our results suggest that kappa opiate
      receptors are involved in naloxone-induced analgesia and are consistent with a
      high degree of plasticity of the opiatergic system.

PMID- 8255905
TI  - Morphine as a cue in associative tolerance to morphine's analgesic effects.
AB  - This study examined the extent to which low doses of morphine paired explicitly
      with high doses would gain associative control over tolerance development in
      rats. Tolerance development was assessed by evaluating dose-response curves to
      the analgesic effects of morphine on the tail-flick test. The results indicated
      that tolerance development was not influenced by the pairing of low doses with
      high doses.

PMID- 8255906
TI  - MK-801 and enantiomers: potential antidepressants or false positives in classical
      screening models?
AB  - In the present experiments, the noncompetitive NMDA antagonist 5-methyl-10,11
      dihydroxy-5H-dibenzo(a,d)cyclo-hepten-5,10-imine (MK-801) and its (+) and (-)
      enantiomers were tested in classical screening models used to detect potential
      antidepressants. The drug and its enantiomers were active in the tail suspension
      test (TST). The racemate was also active in the forced swimming test (FST). The
      effects in these tests occurred, however, at doses with marked stimulant
      activity. Further investigations (reserpine, apomorphine, and yohimbine tests)
      could not confirm the suspected antidepressant activity. Other NMDA antagonists-
      2-amino-7-phosphonoheptanoic acid (AP7), kynurenic acid, and 1-glutamic acid
      diethylester (GDEE)--showed no activity in the TST. These findings throw doubt
      concerning the potential antidepressant activity of MK-801 and other NMDA
      antagonists.

PMID- 8255907
TI  - Benzodiazepine receptor-mediated behavioral effects of nitrous oxide in the rat
      social interaction test.
AB  - The present study was conducted to ascertain whether an anxiolytic effect of
      nitrous oxide was demonstrable in rats using the social interaction test and
      whether this drug effect might be mediated by benzodiazepine receptors. Compared
      to behavior of vehicle-pretreated, room air-exposed rats, rat pairs exposed to
      nitrous oxide showed a generally inverted U-shaped dose-response curve with the
      maximum increase in social interaction encounters occurring at 25% and
      significant increase in time of active social interaction at 15-35%; higher
      concentrations produced a sedative effect that reduced social interaction.
      Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine chlordiazepoxide also
      increased social interaction. Pretreatment with 10 mg/kg of the benzodiazepine
      receptor blocker flumazenil, which alone had no effect, significantly antagonized
      the social interaction-increasing effects of both nitrous oxide and
      chlordiazepoxide. In summary, these findings suggest that nitrous oxide produces
      a flumazenil-sensitive effect comparable to that of chlordiazepoxide and
      implicate central benzodiazepine mechanisms in mediation of the anxiolytic effect
      of nitrous oxide.

PMID- 8255908
TI  - Effects of alprazolam on influenza virus infection in stressed mice.
AB  - The review of the literature shows that stress can adversely affect influenza A
      virus infection. In this report, we study the effects of chronic alprazolam (1
      mg/kg/day), a central benzodiazepine agonist anxiolytic, on the influenza A (PR
      8/34) virus specific immune injury in mice exposed to a chronic auditory
      stressor. Treatment with alprazolam resulted in a significant reduction of stress
      induced increase of virus titters and pulmonary vascular permeability. A
      correlation with the lethality of mice was also observed.

PMID- 8255909
TI  - Greater abundance of serotonin1A receptor in some brain areas of alcohol
      preferring (P) rats compared to nonpreferring (NP) rats.
AB  - Saturable [3H]8-OHDPAT binding to recognition sites of 5-HT1A receptors was shown
      to be higher in cortical membranes of alcohol-preferring (P) than in membranes of
      alcohol-nonpreferring (NP) rats. Neither the P nor the NP lines had been
      previously exposed to ethanol. The increase in binding was mainly due to 40-56%
      higher density or maximum of binding sites (Bmax) without significant change in
      affinity or dissociation constant (Kd) for the radioligand. Although Bmax values
      were also consistently higher in membranes isolated from other brain areas of P
      rats, including hypothalamus, striatum, and hippocampus, the differences did not
      reach statistical significance. Similar to the previously reported lack of
      difference in [3H]ketanserin binding to 5-HT2 receptors in cortical membranes
      from P and NP rats, there were also no significant differences in saturable
      binding of [3H]mesulergine and [3H]LY278584 to recognition sites of 5-HT1C and 5
      HT3 receptors, respectively. Thus, an upregulation of 5-HT1A receptors in
      cerebral cortex and possibly in other brain areas of ethanol-naive P rats appears
      to have occurred as a consequence of the lower 5-HT innervation in this selected
      line of rats (13,15,27,28).

PMID- 8255910
TI  - Bidirectional effects of GABAergic agonists and antagonists on maintenance of
      voluntary ethanol intake in rats.
AB  - The effects of THIP (GABAA agonist) and picrotoxin (GABA antagonist) on the
      maintenance of voluntary ethanol ingestion were examined. Thirty-three male Long
      Evans rats were initially exposed to a screening procedure in which increasing
      concentrations of ethanol (from 2% to 9%) were presented in a free choice with
      water, on an alternate day schedule. Following the screening procedure, the rats
      were exposed to five ethanol presentations at a concentration of 9%, which
      constituted the baseline period, and five additional ethanol presentations during
      which the effects of the GABAergic manipulations were determined (test period).
      During the test period, the animals received IP injections of either 16 mg/kg of
      THIP, 2 mg/kg of picrotoxin or saline. The results suggested that the
      differential GABA manipulations resulted in bidirectional effects on the
      consumption of ethanol. More specifically, the GABAA agonist THIP increased the
      intake of ethanol as compared to baseline measures, while the GABA antagonist
      picrotoxin decreased ethanol intake. Similarly, the administration of THIP
      increased ethanol preference. In contrast, preference for ethanol over water was
      decreased following the administration of picrotoxin. It appears that the effects
      of these GABAergic manipulations are specific to ethanol, since total fluid
      intake was not influenced by the administration of either drug (i.e., THIP or
      picrotoxin). In light of the literature suggesting that THIP and picrotoxin are
      active at different sites within the GABAA chloride-ionophore receptor complex,
      the present findings would suggest that the GABAA receptor may play a role in
      regulating the voluntary intake of ethanol.

PMID- 8255911
TI  - Reward and reinforcement produced by drinking water: role of opioids and dopamine
      receptor subtypes.
AB  - The conditioned place preference procedure was used to evaluate the reinforcing
      properties of drinking in water-deprived rats. Subjects were allowed to drink for
      8 min and were then transferred to place preference cages. In Experiment 1, the
      effects of naloxone and pimozide on drinking-induced place preference were
      analyzed. Animals treated with naloxone, 16 mg/kg, before the conditioning
      sessions showed a place aversion instead of the place preference found in saline
      treated animals. Naloxone also reduced drinking. It was proposed that naloxone
      induced a state of frustrative nonreward. Pimozide, 1 mg/kg, blocked place
      preference and somewhat reduced drinking. In Experiment 2, doses of 1 and 4 mg/kg
      naloxone were used. Both doses blocked place preference. A dose of 4 mg/kg had a
      marginal effect on drinking, while 1 mg/kg lacked effect on this behavior. Thus,
      naloxone may block the establishment of place preference without modifying
      drinking. The effects of the dopamine D1 antagonist SCH23390 and the D2
      antagonist raclopride were studied in Experiment 3. SCH23390 blocked place
      preference and reduced drinking at doses of 0.25 and 0.125 mg/kg. A dose of 0.06
      mg/kg did not affect drinking but inhibited place preference. Raclopride, 0.25
      mg/kg, had the same effects as SCH23390 at the same dose while 0.125 mg/kg
      blocked place preference without affecting drinking. It appears that the effects
      of a D1 and a D2 antagonist are similar. Because the effects of these latter
      drugs also are similar to those obtained with naloxone, it is suggested that both
      dopamine and opioids are important for water-induced reinforcement. Possible
      interactions between these two neurotransmitter systems are discussed.

PMID- 8255912
TI  - Reduction of food intake and morphine analgesia by central glybenclamide.
AB  - Previous research has indicated the presence of a reciprocal relationship between
      food intake and opioid-mediated analgesia. We believe the cellular candidate most
      likely acting as a common mediator of both ingestive and nociceptive behaviors is
      the ATP-sensitive K+ channel (K+ATP). This ion channel appears to be opened by mu
      and delta 1 opioid receptor agonists in the service of analgesia, and closed as
      cellular ATP availability rises. To further examine the role of the K+ATP in the
      relationship between feeding and opioid function, we administered 80 nmol of
      glybenclamide (a K+ATP antagonist) to male SD rats via the lateral ventricle.
      Chow consumption in the treated animals was significantly reduced over the
      following 48 h (F = 2.62, p < 0.013), with the peak effect (78% of control)
      occurring at 6 h. In the tail-flick test, 4 mg/kg morphine sulfate provided
      analgesia of 42.38 +/- 8.4% and 18.89 +/- 7.67% in vehicle and treated animals,
      respectively (p < 0.05, n = 8/group, one-tailed t-test). These results support
      the hypothesis that food intake and analgesia are reciprocally modulated through
      activity at the K+ATP.

PMID- 8255913
TI  - Effects of nicotine cycling on weight loss and regain in male rats.
AB  - Over successive periods of weight loss and regain caused by deprivation and
      refeeding, weight loss becomes slower during deprivation and weight is regained
      quicker during refeeding. One period of nicotine administration and termination
      results in changes in intake and weight gain comparable to that caused by one
      period of food deprivation and refeeding. However, no study has examined the
      effect of multiple periods of nicotine administration and cessation on weight
      loss and regain. The present study examined the effect of repeated cycles of
      nicotine administration and cessation on growth rate. Thirty-two male Sprague
      Dawley rats underwent three nicotine administration cycles. Cycles consisted of 2
      weeks of nicotine or saline followed by 2 weeks of no drug. Nicotine
      administration decreased growth and food consumption, and cessation resulted in a
      resumption of normal growth and intake. However, changes in food consumption and
      body weight were similar across cycles. Thus, although nicotine administration
      and cessation produced reliable changes in food consumption and body weight
      similar to those caused by diet cycling, there were no comparable cumulative
      effects of nicotine cycling on growth rate.

PMID- 8255914
TI  - Behavioral effects of the intraventricular administration of 5-HT and dopamine in
      the common marmoset (Callithrix jacchus).
AB  - The effects of IVT serotonin [5-hydroxytryptamine (5-HT)] and dopamine (DA)
      administration have been studied in rats and marmosets (Callithrix jacchus). In
      rats, 5-HT (114 and 170 micrograms/10 microliters) produced the same behavioral
      effects observed after IP administration of its precursors and agonists. The same
      doses of 5-HT used for rats produced only part of the behavioral effects in
      marmosets after IP administration of 5-HT precursors and agonists. Ataxia,
      vomiting, and decreased motor activity were observed, but not drowsiness or teeth
      chattering. However, IVT administration of DA (400 micrograms/10 microliters
      dose) produced head movements or checking, ataxia, tongue out, and decreased
      motor activity. These findings differ from those observed after IP administration
      of l-DOPA and DA agonists, which increase motor activity.

PMID- 8255915
TI  - Induction of antidepressive activity by monoaminergic transplants in rat
      neocortex.
AB  - To assess the ability of monoaminergic transplants to reduce immobility in the
      forced swimming test (FST), either adrenal medullary tissue, pineal gland tissue,
      or equal volumes of sciatic nerve were transplanted into the rat frontal
      neocortex. In the FST the duration of immobility is thought to indicate the level
      of antidepressant activity, as immobility times are reliably reduced by
      antidepressant therapies. Immobility times were reduced in rats with adrenal
      medullary grafts and pineal grafts to the rat frontal neocortex. In contrast,
      immobility times were not reduced in control sciatic nerve tissue grafts.
      Biochemical analysis using HPLC revealed that pineal-grafted neocortex contained
      higher levels of serotonin (5-HT) and adrenal medullary-grafted neocortex
      contained higher levels of norepinephrine (NE) than sciatic nerve-grafted or
      nongrafted controls. Immunocytochemical studies showed that the monoaminergic
      grafts survived well and continue to produce high levels of monoamines. These
      results support an important role for neocortical 5-HT and NE transmission in
      antidepressant activity and suggest that transplants of monoaminergic-containing
      tissue can reduce biochemical deficits in depression.

PMID- 8255916
TI  - Learned helplessness and in vivo hippocampal norepinephrine release.
AB  - Hippocampal norepinephrine release was measured using in vivo microdialysis in
      rats before and after exposure to inescapable tail shock stress and after testing
      for learned helplessness. Rats that did not develop learned helplessness after
      stress had higher basal norepinephrine release after stress than rats developing
      learned helplessness or than control rats. After the shuttlebox test for learned
      helplessness, K(+)-stimulated norepinephrine release was lower in learned
      helpless than in nonhelpless or control rats. These results confirm an important
      role for the hippocampal noradrenergic system in differential behavioral
      responses to stress.

PMID- 8255917
TI  - An assessment of the interaction between cholecystokinin and the opiates within a
      drug discrimination procedure.
AB  - Recently, cholecystokinin (CCK) has been reported to antagonize a variety of
      opiate-induced effects, including nociception, body shaking, thermoregulation,
      and locomotion. Consistent with these results, a number of CCK antagonists
      potentiate the opiates in a range of behavioral and physiological assessments.
      The present study further examined the interaction between CCK and the opiates
      within the conditioned taste aversion baseline of drug discrimination learning, a
      design that utilizes the stimulus properties of the drug to control consummatory
      behavior. Specifically, animals injected with CCK prior to saccharin-LiCl
      pairings and the CCK vehicle prior to saccharin alone rapidly acquired the CCK
      vehicle discrimination, avoiding saccharin consumption following the
      administration of CCK and consuming the same saccharin solution following the
      vehicle. Although the stimulus properties of CCK did not generalize to either
      naloxone or diprenorphine, morphine blocked and naloxone potentiated CCK's
      stimulus effects. These data are thus consistent with a physiological (rather
      than a pharmacological) interaction between CCK and the opiates.

PMID- 8255918
TI  - Effects of thyroxine and thyroparathyroidectomy on circadian wheel running in
      rats.
AB  - Thyroparathyroidectomized (TPX) and thyroidectomized male rats display shorter
      free-running activity periods and enhanced activity levels. These experiments
      were designed to determine whether this effect is due to the loss of thyroid
      hormones. The running wheel activity of 36 male rats, 19 TPX and 17 sham
      operated, was studied. The animals were kept in constant conditions for 7 weeks
      to obtain baseline data. Half the rats were then injected SC with capsules
      containing T4, while the other half were injected with blanks. All animals were
      then allowed to free-run undisturbed for another 8-9 weeks. TPX rats displayed
      significantly shorter baseline periods (average difference: 0.26 h) and
      heightened activity. Thyroxine treatment significantly lengthened TPX animals'
      cycles (average increase: 0.28 h) but did not affect intact rats' circadian
      rhythms. Thyroxine did, however, significantly decreased the activity levels of
      both TPX and sham-operated rats. These findings indicate that changes in TPX
      rats' activity cycles are caused by a reduction in thyroid hormones and that
      thyroxine acts on activity rhythms and levels by different mechanisms.

PMID- 8255919
TI  - Thyroid and thyroxine effects on adrenoreceptors in relation to circadian
      activity.
AB  - Experiments were conducted to ascertain if changes in central adrenergic
      receptors could be associated with altered circadian activity patterns induced by
      thyroparathyroidectomy (TPX) and thyroxine. An initial experiment used TPX and
      sham-operated rats that had been exposed to dim red light for 7 months. The alpha
      and beta receptor densities were compared in the suprachiasmatic nuclei (SCN),
      preoptic (PO), septum, and caudate-putamen. TPX animals showed significant
      reductions in beta 1 and beta 2 receptor densities in SCN and PO, and alpha 1
      densities in SCN, but no other changes. A second experiment, lasting 4 months,
      examined the effects of thyroxine, which has been shown to reverse the period
      shortening effects of TPX surgery. Thyroxine significantly increased beta 1
      receptors in both the SCN and ventromedial hypothalamus (VMH), the only regions
      that displayed significant reductions in TPXs during the second experiment.
      Increases of sevenfold and threefold were observed in the SCNs of TPXs and shams,
      respectively, but thyroxine's action in the VMH was limited to TPX animals, an
      effect that mimics thyroxine's action on circadian activity rhythms.

PMID- 8255920
TI  - Absence of impairments in spatial and temporal discrimination learning in Lewis
      rats after chronic ethanol consumption.
AB  - Many studies reported that chronic ethanol consumption leads to cognitive
      dysfunction in rodents. It has been suggested that the effects of chronic ethanol
      consumption resemble those of aging because of the behavioral and neurochemical
      similarities between the two processes. The present study examined the effects of
      a chronic ethanol treatment (20% aqueous solution) in Lewis rats on performance
      in three different tasks: the Morris spatial navigation task, a cone-field task,
      and a temporal discrimination task. Although an age-related deficit was found in
      water escape learning, chronic ethanol consumption did not affect the performance
      of adult and old rats. The results of this experiment were, however, not
      conclusive. No differences between old control and ethanol-treated rats were
      found for spatial (cone-field task) and temporal discrimination learning.
      However, old ethanol-treated rats showed a transient tendency to perseverate in
      the temporal discrimination task. The present results are at variance with the
      generally found cognitive impairments after chronic ethanol consumption using
      aqueous solutions. It is suggested that the effects of ethanol could be related
      to strain of rat, task complexity, method of ethanol administering, and housing
      conditions and may explain the discrepancy between results.

PMID- 8255921
TI  - EtOH self-administration in anticipation of noise stress in C57BL/6J mice.
AB  - C57BL/6J mice were studied for self-administration of ethanol (EtOH) during a
      signal period that preceded delivery of an environmental stressor (noise) in the
      home cage. Animals were given 5 weeks of conditioning in which a 5-min period of
      75-dB pulsed noise (SIGNAL) preceded a 20-min period of more intense, 90-dB
      pulsed noise (NOISE) five times daily. EtOH (10% w/v) was then provided in a
      choice procedure, and drink tube contacts were monitored by computer. Mice that
      had received the 5 weeks of SIGNAL and NOISE pairings showed an increase in EtOH
      seeking behavior, as reflected in EtOH tube contacts during the SIGNAL period.
      The increase was significant as compared to contacts during baseline or QUIET
      periods and also as compared to contacts during the same period for control
      (Ctrl) mice that had received only the 75-dB SIGNAL during conditioning. A
      subsequent test for passive avoidance confirmed that the 75-dB SIGNAL was
      aversive for mice that had received noise conditioning but not for Ctrl mice. In
      sum, the results were in accord with a priori predictions that mice would not
      show increased EtOH tube contacts during occurrence of intense noise itself but
      would show increased contacts during the signal that preceded noise. These
      results were interpreted as preliminary evidence that C57BL/6J mice show self
      administration of EtOH in anticipation of an environmental stressor.

PMID- 8255922
TI  - Successful use of S20098 and melatonin in an animal model of delayed sleep-phase
      syndrome (DSPS).
AB  - In human delayed sleep-phase syndrome (DSPS), sleep onset and wake times occur
      far later than normal. In the population, DSPS may be an important contributor to
      complaints of sleep onset insomnia. We previously reported an animal model of
      DSPS in laboratory rats in which the onset of nocturnal activity is delayed by
      several hours [negative phase angle difference (PAD)]. The effect of melatonin 1
      mg/kg SC and S20098 (Servier) 1 and 3 mg/kg on the negative PAD was investigated
      over 22 days of injections. In comparison to control injections of
      dimethylsulfoxide (DMSO), both melatonin and S20098 over approximately 9 days
      phase advanced the onset of activity toward the onset of darkness. At cessation
      of injections, activity onset delayed over approximately 11 days back toward, but
      as a group did not reach the original PAD. This effect of melatonin on the phase
      angle of entrained rats is consistent with its effects on delayed sleep in
      humans. It is likely, therefore, that S20098 may be of use to ameliorate DSPS in
      humans.

PMID- 8255923
TI  - Acute cocaine toxicity: the effect of agents in non-seizure-induced death.
AB  - Death from cocaine intoxication results from one or more of the multiple
      mechanisms including seizures, cardiovascular collapse, or apnea. In the free
      moving rat model, continuous seizures are a major cause of death. To study other
      mechanisms of death unrelated to seizures in this model, we suppressed lethal
      seizures with diazepam (DZP) and investigated the effect of several
      pharmacological agents. Rats were pretreated with vehicle alone, diazepam 5 mg/kg
      alone, or a combination of DZP plus either nifedipine (NIFD) 2 mg/kg, propranolol
      (PROP) 10 mg/kg, or prazosin (PRAZ) 5 mg/kg. Five minutes after pretreatment, all
      animals received cocaine 100 mg/kg. Each test group consisted of 15 animals and
      all agents were given IP. Two animals in each group had cortical electrodes
      implanted. Animals that received vehicle followed by cocaine had 100% incidence
      of seizures and death. Those rats that received DZP alone followed by cocaine had
      no seizures and 53% death. Rats that received DZP plus NIFD or DZP plus PROP had
      suppression of seizures but no significant change in the incidence of death. The
      group that received DZP and PRAZ followed by cocaine had no seizures and 13%
      incidence of death (p < 0.001). Electroencephalogram recordings showed cortical
      electrical spike activity or spike-and-wave afterdischarges in all animals
      clinically observed to have seizures. In the absence of clinical seizure
      activity, no significant cortical spike activity was noted. It is concluded that
      animals protected from seizures with diazepam can still have nonseizure deaths
      after high-dose cocaine. The incidence of death in these animals is not reduced
      with nifedipine or propranolol pretreatment but is reduced with prazosin
      pretreatment.

PMID- 8255924
TI  - Effects of pindobind 5-hydroxytryptamine1A (5-HT1A), a novel and potent 5-HT1A
      antagonist, on social and agonistic behaviour in male albino mice.
AB  - In view of inconsistent results reported for 5-hydroxytryptamine1A (5-HT1A)
      receptor involvement in murine social conflict, this study examined the effects
      of N1-(bromoacetyl)-N8-[3-(4-indolyloxy)-2- hydroxypropyl]-(Z)-1,8-diamino-p
      menthane (pindobind) 5-HT1A, a novel 5-HT1A antagonist, on agonistic and social
      behaviour in mice. Employing a resident-intruder paradigm, administration of
      pindobind 5-HT1A (0.5-10 mg/kg) to resident animals produced a reduction in
      offensive sideways and chasing behaviour. Defensive postures were unchanged
      except for evasion, which was reduced. Within social behaviour, nonspecific
      social behaviour and following behaviour were reduced while stretch/attend
      behaviour was enhanced. Nonsocial behavioural changes included an increase in
      resident cage exploration and rearing. Intruder data indicated no significant
      change in offensive behaviours, an attenuation of defensive sideways posturing
      and evasion, decreases in attend behaviour, and increases in cage exploration,
      rearing, and digging. Results are discussed in relation to the effects of 5-HT1A
      receptor (ant)agonism on murine offensive behaviour.

PMID- 8255925
TI  - Interaction of the competitive AMPA receptor antagonist NBQX with hexobarbital.
AB  - IP administration of hexobarbital to rats caused a mean sleeping time of 93.6 min
      (SD 21.5). IV infusion of 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline
      (NBQX) at a dose rate of 0.11 mg/kg/min starting 30 min after administration of
      hexobarbital prolonged the mean sleeping time to 132.2 min (SD 14.9). Dose rates
      of 0.33 and 1.10 mg/kg/min prolonged the mean sleeping times to 176.4 min (SD
      33.3) and 444.1 min (SD 72.0), respectively. Measured 180 and 450 min after the
      start of the study, there were no differences in the plasma concentrations of
      hexobarbital in groups receiving hexobarbital alone compared to groups receiving
      the high-dose rate of NBQX starting 30 min after administration of hexobarbital.
      The present results demonstrate that by IV infusion NBQX dose dependently
      prolonged the sleeping time of hexobarbital. There were no indications of
      interactions on hexobarbital elimination of either isomer. It is therefore likely
      that NBQX acts synergistically with hexobarbital to depress the central nervous
      activity.

PMID- 8255926
TI  - Involvement of brain tryptophan hydroxylase in the mechanism of hibernation.
AB  - Marked changes were revealed in the activity of the key enzyme in serotonin
      biosynthesis, tryptophan hydroxylase (TPH), during entry into hibernation,
      hibernation, and arousal in ground squirrels (Citellus erythrogenys). An increase
      in TPH activity was found in the midbrain, hippocampus, and striatum during the
      prehibernation period in euthermic ground squirrels. A further increase in TPH
      activity was observed during the entry into hibernation. Significant elevation
      was found not only in potential TPH activity measured at the incubation
      temperature of 37 degrees C but also at incubation temperature of 7 degrees C,
      approximating the body temperature in hibernation. Vmax in the midbrain of
      hibernating animals was about 50% higher than in active ones without significant
      changes in Km. Thus, brain TPH maintains functionality during torpidity and is
      activated before the entry into hibernation. The results support the idea that
      brain serotonin is crucially involved in the transition to and the maintenance of
      the hibernation state.

PMID- 8255927
TI  - Effects of (S)-alpha-fluoromethylhistidine and (R)-alpha-methylhistamine on
      locomotion of W/Wv mice.
AB  - We studied the effects of inactivators of the central histaminergic neuron
      system, (R)-alpha-methylhistamine, a histamine H3 receptor agonist, and (S)-alpha
      fluoromethylhistidine, a histamine synthesis inhibitor, on locomotor activity and
      brain histamine content of mast cell-deficient W/Wv mice using a recently
      developed high-performance liquid chromatography system coupled with a
      fluorometric detector. IP injection of (R)-alpha-methylhistamine (6-50 mg/kg)
      increased brain histamine content after 1 h but caused no significant change in
      locomotor activity. IP injection of (S)-alpha-fluoromethylhistidine decreased
      brain histamine content at doses of 6-50 mg/kg and locomotor activity at doses of
      12.5-50 mg/kg. However, locomotor activity was decreased significantly (in
      Student's t-test) by sequential administrations of (S)-alpha
      fluoromethylhistidine (6 mg/kg) and (R)-alpha-methylhistamine (12.5 or 25 mg/kg),
      but not by (S)-alpha-fluoromethylhistidine (6 mg/kg) and other doses of (R)-alpha
      methylhistamine (6 or 50 mg/kg). These results support the hypothesis that the
      central histaminergic neuron system is involved in the control of spontaneous
      locomotion or alertness.

PMID- 8255928
TI  - Report of the results of a double-blind, randomized, single-dose trial of a
      topical 2% escin gel versus placebo in the acute treatment of experimentally
      induced hematoma in volunteers.
AB  - The efficiency of topically applied 2% escin gel in reducing tenderness to
      pressure on experimentally induced hematoma is demonstrated. A double-blind,
      randomized signal dose trial versus placebo in healthy volunteers was used.

PMID- 8255929
TI  - Sedative effect of galphimine B, a nor-seco-triterpenoid from Galphimia glauca.
AB  - Galphimia glauca Cav. (Malpighiaceae) is used in Mexican traditional medicine as
      a sedative in the treatment of mental disorders. Sedative properties of a
      methanolic extract of the aerial parts of this plant have been established in
      animal trials and an active compound, named galphimine B, has already been
      isolated. This compound was submitted to neuropharmacological testing, where it
      was shown that galphimine B had no significant effect as an anticonvulsant, while
      it exhibited a strong depressant activity on the nervous system.

PMID- 8255930
TI  - Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia
      euchroma.
AB  - Four antiplatelet components were isolated from Arnebia euchroma. They inhibited
      the aggregation of washed rabbit platelets caused by collagen, arachidonic acid,
      platelet-activating factor, ADP, or thrombin. The potency of inhibiting collagen
      induced platelet aggregation is in the following order: acetylshikonin (IC50 =
      2.1 microM), teracrylshikonin (2.8 microM), beta, beta-dimethylacrylshikonin (4.2
      microM), and shikonin (10.7 microM). In rat aorta, acetylshikonin and shikonin
      inhibited high potassium and norepinephrine-induced contractions, while beta,
      beta-dimethylacrylshikonin and teracrylshikonin potentiated the phasic
      contraction caused by norepinephrine.

PMID- 8255931
TI  - Antihypertensive principles from the leaves of Melastoma candidum.
AB  - Three active principles were isolated from the leaf of Melastoma candidum using
      the screening of hypotensive effects on spontaneously hypertensive rats (SHR).
      Intravenous injection of castalagin, procyanidin B-2, or helichrysoside into SHR
      lowered the mean blood pressure in a dose-dependent manner, with helichrysoside
      being the most potent compound. Plasma noradrenaline (NA) levels, both basal in
      SHR and elevated in normal rats through cold-stress stimulation, were attenuated
      by these compounds in a way which was not influenced by adrenalectomy. Decrease
      of NA release from sympathetic nerves was assumed to be responsible. Moreover,
      the hypertensive effect of various vasoconstrictors in anesthetized rats was
      reduced by helichrysoside. The same results were also observed in castalagin or
      procyanidin B-2 treated animals. The results indicate that the three principles
      possess the ability to lower blood pressure through a decrease of sympathetic
      tone as well as due to direct vasodilatation in SHRs.

PMID- 8255932
TI  - Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica
      charantia on normal and diabetic model rats.
AB  - Extracts of Momordica charantia fruit pulp, seed, and whole plant were tested for
      their hypoglycemic effects on normal and diabetic rat models. The results show
      that during the oral glucose tolerance test the peak blood glucose values in rats
      are obtained much earlier (15-45 min) than in human subjects (around 60 min).
      Pulp juice of M. charantia lowered fasting blood glucose levels in normal rats (p
      < 0.05 at 120 min); the effect was more pronounced with the saponin-free methanol
      extract of the pulp juice (p < 0.05 at 60 min and p < 0.01 at 120 min). The pulp
      juice also had a significant hypoglycemic effect in the glucose-fed normal rats
      when the extract was fed 45 minutes before the oral glucose load [percentage
      increments over basal value (M +/- SE): 85 +/- 10 in the control group vs. 54 +/-
      7 in the pulp juice group, p < 0.01]. In the IDDM model rats the pulp juice had
      no significant effect on blood glucose levels either in fasting or postprandial
      states. In the NIDDM model rats the saponin-free methanol extract of juice
      produced a significant hypoglycemic effect both in fasting (p < 0.05 at 120 min)
      and in postprandial states (sum of percentage increments over basal value: 140 +/
      26 in the control vs. 71 +/- 7 in the pulp juice group, p < 0.05). Methanol
      extracts of seed and of whole plant, and saponin-free methanol extract of whole
      plant produced no hypoglycemic effects in normal or IDDM model rats either in
      fasting or in postprandial states.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255933
TI  - Evaluation of the liver protective potential of piperine, an active principle of
      black and long peppers.
AB  - Piperine, an active alkaloidal constituent of the extract obtained from Piper
      longum and Piper nigrum, was evaluated for its antihepatotoxic potential in order
      to validate its use in traditional therapeutic formulations. This plant principle
      exerted a significant protection against tert-butyl hydroperoxide and carbon
      tetrachloride hepatotoxicity by reducing both in vitro and in vivo lipid
      peroxidation, enzymatic leakage of GPT and AP, and by preventing the depletion of
      GSH and total thiols in the intoxicated mice. Silymarin, a known hepatoprotective
      drug was tested simultaneously for comparison. Piperine showed a lower
      hepatoprotective potency than silymarin.

PMID- 8255934
TI  - Perfusion with picroliv reverses biochemical changes induced in livers of rats
      toxicated with galactosamine or thioacetamide.
AB  - Perfusion of liver of rats toxicated with galactosamine or thioacetamide with a
      0.02% solution of picroliv (glycoside fraction of Picrorhiza kurroa) for 30 min
      (1 ml/min; 6 mg/rat), significantly reversed toxicant-induced changes in the
      activities of several enzymes. Galactosamine induced increases in the activities
      of alkaline phosphatase, gamma-glutamyl transpeptidase, acid ribonuclease, acid
      phosphatase, succinate dehydrogenase and decreases in the activities of Na(+)
      K(+)-adenosine triphosphatase (ATPase) and glucose-6-phosphatase (reversed by 40
      87%). Similarly, thioacetamide-induced inhibitions of the activities of Na(+)
      K(+)-ATPase, Ca(++)-ATPase, Mg(++)-ATPase, succinate dehydrogenase and elevations
      in the activities of alkaline phosphatase, gamma-glutamyl transpeptidase, and
      acid ribonuclease were also significantly reversed. A significant reversal of the
      toxicants-induced decrease in [14C]-leucine incorporation was also observed.
      These results indicate that picroliv can also reverse D-galactosamine- or
      thioacetamide-induced hepatic damage in rats.

PMID- 8255935
TI  - Protective effect of Dunaliella bardawil on water-immersion-induced stress in
      rats.
AB  - The functional activity of a natural isomer mixture as compared with synthetic
      all-trans beta-carotene in rats was investigated in a rat model produced by water
      immersion restraint stress. Five-week-old male rats were fed diets supplemented
      with synthetic all-trans beta-carotene, dry Dunaliella bardawil, and purified
      natural beta-carotene from D. bardawil at equivalent levels of beta-carotene.
      After the rats were fed diets containing up to 0.1% beta-carotene for 2 weeks,
      they were restrained in a wire cage and immersed in a 23 degree C water bath for
      20 h. Liver analyses indicated that rats showed higher accumulations of the algal
      beta-carotene isomer mixture than of the synthetic all-trans beta-carotene.
      Dunaliella bardawil and purified natural beta-carotene significantly decreased
      the gastric mucosal lesions. Synthetic beta-carotene did not decrease the
      lesions. These results suggest that the gastric cytoprotective effect of beta
      carotene depends on the amount of beta-carotene accumulated in the body.

PMID- 8255936
TI  - Suppression by kampo medicines in preneoplastic mammary hyperplastic alveolar
      nodules of SHN virgin mice.
AB  - Sho-saiko-to (SST), Keishi-bukuryo-gan (KBG), and Shakuyaku-kanzo-to (SKT) are
      Japanese modified traditional Chinese herbal medicines (Kampo medicines)
      consisting of 7, 5, and 2 medical plants, respectively. It is known that the
      hyperplastic alveolar nodule (HAN) is a representative preneoplastic state in the
      mammary glands of mice. We examined the effects of SST, KBG, and SKT on the
      formation and growth of HAN in a high-mammary-tumor strain of SHN virgin mice.
      Oral administration of SST for 60 days beginning at 90 days of age reduced the
      number and area of HAN and mammary thymidylate synthetase activity with a
      reduction of serum prolactin level. There was little difference between the other
      experimental groups and the control in the formation and growth of HAN and the
      enzyme activities. These results indicate that SST may have a preventive effect
      on malignant mammary transformations.

PMID- 8255937
TI  - Biological activities of terthiophenes and polyynes from the Asteraceae.
AB  - We evaluated a number of terthiophenes and polyynes, from the Asteraceae, for
      biological activities against microorganisms, viruses, and tumor cells, with and
      without the aid of UVA (long wavelength ultraviolet) radiation. The
      terthiophenes, which represented the basic alpha-terthienyl nucleus with simple
      side chains, showed impressive UVA-dependent activities, some of which were
      superior to alpha-terthienyl itself. In contrast, the polyynes had no significant
      biological activity, with or without UVA. We believe that these terthiophenes
      would be worthwhile evaluating in animal models of infectious diseases.

PMID- 8255938
TI  - Three non-phenolic diarylheptanoids with anti-inflammatory activity from Curcuma
      xanthorrhiza.
AB  - Bioassay-guided fractionation of a hexane extract of the rhizomes of Curcuma
      xanthorrhiza Roxb. (Zingiberaceae) led to the isolation of three non-phenolic
      diarylheptanoids, identified mainly by high-field 1H-NMR as trans-trans-1,7
      diphenyl-1,3-heptadien-4-one (alnustone), trans-1,7-diphenyl-1-hepten-5-ol, and
      trans,trans-1,7-diphenyl-1,3-heptadien-5-ol. The latter is reported for the first
      time as a plant constituent. Germacrone, curzerenone, and cinnamaldehyde were
      also isolated and identified. The three diarylheptanoids all exerted significant
      anti-inflammatory activity in the assay of carrageenin-induced hind paw edema in
      rats.

PMID- 8255939
TI  - Biologically active compounds from the Euphorbiaceae; Part 1. Triterpenoids of
      Euphorbia nicaeensis subsp. glareosa.

PMID- 8255940
TI  - Piperine: a potent inhibitor of Leishmania donovani promastigotes in vitro.

PMID- 8255941
TI  - Vasodilator effects of bisbenzylisoquinoline alkaloids from Stephania
      cepharantha.

PMID- 8255942
TI  - [Personality as a predictor of therapy effectiveness in endogenous depression].
AB  - On the basis of personality assessment (MMPI, MPI) patients with endogenous
      depression were shown to react differently to treatment. Women who obtained low
      scores on the Lie (L), Depression (D) and Repression (R) scales as well as high
      scores on the Psychopathic deviate (Pd) and Alcoholism (Mac) scales had better
      therapy outcomes. On the other hand from among men with endogenous depression
      those reacting better to treatment were those who obtained low scores on the
      Depression (D) and high scores on the Mania (Ma) scales.

PMID- 8255943
TI  - [Influence of personality traits of female patients hospitalized with coronary
      disease upon their susceptibility to iatrogenic psychical trauma].
AB  - The analysed problem dealt with personality determinants of susceptibility to
      iatrogenic psychical trauma. A group of 35 female patients with coronary disease
      and another group consisting of 35 healthy women were tested with C.D.
      Spielberger's State-Trait Anxiety Inventory, Z. Bizon's Questionnaire of Neurotic
      Symptoms, J.B. Rotter's I-E Scale, and the author's own method for the
      determination of susceptibility to iatrogenic psychical trauma. In comparison
      with healthy women, the patients displayed significantly higher level of anxiety
      both as a state and as a trait, lower level of psychical endurance, more external
      sense of control and higher susceptibility to iatrogenic trauma. More over, the
      patients with lower psychical endurance and external sense of control displayed
      high susceptibility to iatrogenic psychical trauma.

PMID- 8255944
TI  - [The psychological meaning of abnormal behavior in mental retardation].
AB  - The aim of the article is to encourage psychiatrists to follow the
      psychopathological approach to mental retardation. According to the author's
      opinion it is impossible to explain mental retardation only by using neurological
      and genetic categories. Mental retardation belongs to the group of psychological
      disorders like the psychoses and the neuroses. This disorder is characterized by
      pathological organisation of personality, that inhibits the development of the
      cognitive functions. The author presents the conditions of life in social care
      homes (where the basic needs concerning dignity, love and freedom are absent) as
      an example of the factors pathologizing the personality. She explains the
      psychological meaning of some abnormal behaviours by persons with mental
      retardation living in such conditions.

PMID- 8255945
TI  - [Prevalence of the dementia syndrome among elderly people in an urban area. A
      pilot study].
AB  - Data was collected from a group of 100 randomly selected subjects from a city
      population above the age of 65 years. The aim of the research was to prove the
      reliability and validity of the research tools: the Folstein's MMSE and the
      Blessed's IMC. Thirty subjects were eliminated from the sample the remaining 70
      were grouped according to gender for further analysis. The intergroup correlation
      indicated a high reliability of both tests. The hypothesis about the normal
      distribution of both groups was supported. In eleven subjects the results
      indicated the existence of a dementia syndrome f not great severity.

PMID- 8255947
TI  - [Buspirone in the treatment of Generalized Anxiety Disorders].
AB  - A group of 86 patients, diagnosed with GAD, were treated with doses of 25 mg of
      Buspirone or 20 mg of Diazepam in a blind study. Comparative efficacy of both
      drugs and placebo was conducted on 40 patients (archival data). Greater efficacy
      of Diazepam and Buspirone in states of chronic anxiety was indicated. There were
      no differences in the intensity of efficacy of both drugs. The effects of
      Buspirone were equally strong but more general on psychic and somatic anxiety,
      with the exception of sleep disturbance, in comparison with Diazepam. The
      efficacy of Buspirone increased after 2 weeks of application. No serious or
      intensified adverse effects were observed. The incidence of adverse effects was
      slightly higher in the Buspirone group, and included dizziness, weakness and
      disturbance of sleep. There were no significant changes in physical examination
      or laboratory measures.

PMID- 8255946
TI  - [Problems concerning the use of alcohol and other dependence including drugs used
      by children and adolescents of the region of Lodz in the years 1980-1992 in the
      light of epidemiological studies by the Institute of Mental Hygiene of the
      Military Academy of Medicine].
AB  - In the years 1980-1992 the authors with the cooperation of persons quoted in the
      References, investigated children from elementary and secondary schools, among
      them particularly children of unemployed parents, recruits, students of high
      schools and juvenile alcoholics and drug addicts. They found a decrease in the
      age of initiation of the use of alcohol and drugs in the last years, significant
      increase in the use of alcohol in all investigated groups and described the
      common reasons and mechanisms of development of dependency among children and
      youth.

PMID- 8255948
TI  - [Clinical evaluation of Clozapol in the treatment of schizophrenia].
AB  - The clinical research on Klozapol included 28 patients (17 female and 11 male)
      diagnosed as suffering from schizophrenia. The drug was tested in open trial
      without comparison with original medication. This research revealed a high
      therapeutic effectiveness of Klozapol in roughly 2/3 of the cases. The side
      effects which have been observed were slight, and occurred with similar frequency
      as Leponex. The hematological complications such as granulocytopenia and
      agranulocytosis were not observed. The range of the doses was quite wide between
      50 and 900 mg per day.

PMID- 8255949
TI  - [Controversy regarding private practice in psychiatry and psychotherapy: notes
      from panel discussion].

PMID- 8255950
TI  - Dissociated overt and covert recognition as an emergent property of a lesioned
      neural network.
AB  - Covert recognition of faces in prosopagnosia, in which patients cannot overtly
      recognize faces but nevertheless manifest recognition when tested in certain
      indirect ways, has been interpreted as the functioning of an intact visual face
      recognition system deprived of access to other brain systems necessary for
      consciousness. The authors propose an alternative hypothesis: that the visual
      face recognition system is damaged but not obliterated in these patients and that
      damaged neural networks will manifest their residual knowledge in just the kinds
      of tasks used to measure covert recognition. To test this, a simple model of face
      recognition is lesioned in the parts of the model corresponding to visual
      processing. The model demonstrates covert recognition in 3 qualitatively
      different tasks. Implications for the nature of prosopagnosia, and for other
      types of dissociations between conscious and unconscious perception, are
      discussed.

PMID- 8255951
TI  - How do we know that we know? The accessibility model of the feeling of knowing.
AB  - Even when Ss fail to recall a solicited target, they can provide feeling-of
      knowing (FOK) judgments about its availability in memory. Most previous studies
      addressed the question of FOK accuracy, only a few examined how FOK itself is
      determined, and none asked how the processes assumed to underlie FOK also account
      for its accuracy. The present work examined all 3 questions within a unified
      model, with the aim of demystifying the FOK phenomenon. The model postulates that
      the computation of FOK is parasitic on the processes involved in attempting to
      retrieve the target, relying on the accessibility of pertinent information. It
      specifies the links between memory strength, accessibility of correct and
      incorrect information about the target, FOK judgments, and recognition memory.
      Evidence from 3 experiments is presented. The results challenge the view that FOK
      is based on a direct, privileged access to an internal monitor.

PMID- 8255952
TI  - The nature and function of interoceptive signals to feed: toward integration of
      physiological and learning perspectives.
AB  - The idea that different states of energy need give rise to distinct interoceptive
      sensations has been basic to many accounts of the physiological and the learned
      controls of feeding. Yet, a number of difficulties have complicated attempts to
      provide direct evidence for this view. The present article describes a research
      strategy that confirms that food deprivation states produce salient interoceptive
      stimuli in rats. The implications of this research for the physiological origins
      of energy state signals, the brain structures involved with processing energy
      state information, and the manner in which signals of energy need influence
      feeding were considered. The possibility that food deprivation cues influence
      feeding by modulating the activation of associations involving external events
      and their postingestive aftereffects was discussed with reference to earlier
      associative accounts of the function of hunger signals.

PMID- 8255953
TI  - Adolescence-limited and life-course-persistent antisocial behavior: a
      developmental taxonomy.
AB  - A dual taxonomy is presented to reconcile 2 incongruous facts about antisocial
      behavior: (a) It shows impressive continuity over age, but (b) its prevalence
      changes dramatically over age, increasing almost 10-fold temporarily during
      adolescence. This article suggests that delinquency conceals 2 distinct
      categories of individuals, each with a unique natural history and etiology: A
      small group engages in antisocial behavior of 1 sort or another at every life
      stage, whereas a larger group is antisocial only during adolescence. According to
      the theory of life-course-persistent antisocial behavior, children's
      neuropsychological problems interact cumulatively with their criminogenic
      environments across development, culminating in a pathological personality.
      According to the theory of adolescence-limited antisocial behavior, a
      contemporary maturity gap encourages teens to mimic antisocial behavior in ways
      that are normative and adjustive.

PMID- 8255954
TI  - A queue-series model for reaction time, with discrete-stage and continuous-flow
      models as special cases.
AB  - This article presents a new reaction time model that includes both sequential
      stage (discrete) and overlapping-stage (continuous-flow) models as special cases.
      In the new model, task performance is carried out by a series of distinct
      processing stages, each of which functions as a queue. A stimulus conveys 1 or
      more distinct components of information (e.g., features), and each stage can
      begin processing as soon as it receives 1 component from its predecessor. If a
      stimulus activates only 1 component, successive stages operate in strict
      sequence; if it activates multiple components, successive stages operate with
      temporal overlap. Within this class of models, experimental factors affecting
      different processing stages always have additive effects on reaction time with
      sequential stages but rarely do so with overlapping stages. Within this class of
      models, then, observations of factor additivity support discrete-stage models.

PMID- 8255955
TI  - Reflectivity and learning from aversive events: toward a psychological mechanism
      for the syndromes of disinhibition.
AB  - Gorenstein and Newman (1980) proposed that poorly modulated responding for reward
      is the common diathesis underlying disinhibited behavior in several traditionally
      distinct person categories: psychopathy, hysteria, early onset alcoholism,
      childhood hyperactivity, and nonpathological impulsivity (e.g., extraversion).
      The authors extend this proposal by theorizing a psychological mechanism that
      highlights relations among disinhibition, reflection, and failures to learn from
      aversive feedback. The hypothesized mechanism is presented as 4 generic stages of
      response modulation: the dominant response set, the reaction to an aversive
      event, the subsequent behavioral adaptation, and the immediate and long-term
      consequences of reflection, or the lack thereof. The mechanism has implications
      for disinhibited individuals' impulsivity and provides a point of departure to
      study factors responsible for similarities and differences among these syndromes.

PMID- 8255956
TI  - On measuring (in)dependence of cognitive processes.
AB  - The authors provide a critical evaluation of the use of stochastic independence
      in psychological research. Specifically, they consider problems of confirming the
      null hypothesis, power of the statistical test, Simpson's paradox, and between
      subjects and within-subject correlations. These problems are discussed in the
      context of research on theories of memory and cognitive development and
      illustrated with data on reasoning-remembering relationships. The authors
      conclude that demonstrations of response independence do not, by themselves,
      provide sufficient grounds for deciding whether a single process or multiple
      processes are necessary to account for performance. Instead, they argue that
      formal models are necessary if findings of (in)dependence are to be interpreted
      meaningfully in terms of underlying theoretical processes.

PMID- 8255957
TI  - A neural-network model enabling sensorimotor learning: application to the control
      of arm movements and some implications for speech-motor control and stuttering.
AB  - Low-level motor control is defined as adapting an organism to the unique physical
      properties of its own limbs. The two-jointed arm serves to exemplify that
      effective low-level motor control demands a neurally medicated inversion of the
      dynamics, as well as of the kinematics, of a limb system. Reflex-like processing-
      that is, feedforword of either actual or predicted proprioceptive signals--is
      thereby assumed to be the principle of the dynamics control. As regards speech
      motor control, the overall tool transformation is assumed to transform the force
      pattern of the articulatory muscles into speech sounds. Like the arm model, the
      vocal-tract transformation thus defined is also divided into two parts, namely
      the transformation relating the muscle forces to the mechanospatial states of the
      vocal tract (which is analogous to the forward dynamics including natural
      interarticulatory couplings), and the transformation relating the mechanospatial
      states to the speech sounds. Low-level speech-motor control, then, needs to
      invert both transformations, each of which can be learned by means of the self
      imitation algorithm. Erroneous learning can fail to decouple interarticulatory
      coupling and therefore lead to abnormal feedback loops through the reflex-like
      operating neural network, which in turn can cause stuttering if audiophonatoric
      coupling is involved in learning.

PMID- 8255958
TI  - The effects of alphabetic-reading competence on language representation in
      bilingual Chinese subjects.
AB  - The metaphonological abilities of two groups of bilingual Chinese adults residing
      in the Netherlands were examined. All subjects were able to read Chinese
      logograms, but those in the alphabetic group had, unlike those in the non
      alphabetic group, also acquired some competence in reading Dutch. In Experiment
      1, strong, significant differences between the two groups were obtained in the
      task of deleting the initial consonant of a Dutch spoken pseudo-word and also in
      a task consisting of segmenting a sentence into progressively smaller fragments,
      but there was no difference in a rhyme--nonrhyme classification task with pairs
      of Dutch words. In the latter task, the subjects in the two groups performed at a
      near-ceiling level. In Experiment 2, a significant difference was obtained again
      for the consonant-deletion task and no difference with an initial syllabic-vowel
      deletion task, but the non-alphabetic subjects performed at a significantly lower
      level than the alphabetic subjects in the rhyme-judgement task. Taken together,
      these results are consistent with the earlier evidence that learning a non
      alphabetic orthography does not promote awareness of the segmental structure of
      utterances. On the other hand, they confirm, for a population of Chinese readers,
      the conclusion drawn earlier from work with illiterate subjects that explicit
      instruction is more critical for the development of segmental representations of
      language than of representations of higher levels such as those of rhymes and
      syllables.

PMID- 8255959
TI  - Chest pain, normal coronaries: whose problem?

PMID- 8255960
TI  - Campylobacter jejuni and Guillain-Barre syndrome.
AB  - Campylobacter jejuni is the most frequently identified bacterial cause of
      gastroenteritis in the UK, and commonly precedes Guillain-Barre syndrome (GBS).
      There is some evidence that the resultant neurological disease may be a more
      severe variant of GBS with predominant axonal degeneration. Crossreactivity
      between neural antigens and C. jejuni may be one of the mechanisms by which GBS
      is triggered. Unravelling the immunopathogenesis of GBS following C. jejuni
      enteritis may shed light on the way in which bacterial infections induce
      autoimmune disease.

PMID- 8255961
TI  - Microbiological lung surveillance in mechanically ventilated patients, using non
      directed bronchial lavage and quantitative culture.
AB  - We surveyed bronchial microflora by alternate-day, non-directed bronchial lavage
      (NBL) in 150 patients requiring mechanical ventilation on an intensive care unit.
      This simple technique uses a 20 ml non-bronchoscopic lung lavage, then
      quantitative bacterial culture. NBL bacteriological findings were identical to
      those obtained by same-day bronchoscopic broncho-alveolar lavage on 16/20
      occasions. Using serial NBLs, the bronchial bacterial population was
      characterized during 65 episodes of pneumonia defined by clinical and
      retrospective criteria. Mean bacterial colony counts increased significantly
      during the 2 days preceding the clinical onset of pneumonia, from < or = 10(3)
      cfu/ml to > or = 10(5) cfu/ml (p < 0.05). In 51 patients showing a clinical
      response to antibiotic treatment, mean colony counts fell significantly after
      antibiotic initiation (p < 0.05). By contrast, in 14 patients who showed
      progressive clinical deterioration or relapse, there was no significant fall in
      NBL counts, and serial NBLs revealed antibiotic resistance or superinfection. The
      surveillance data altered clinical management in 42% of patients. Positive NBLs
      guided the choice of antibiotics, whilst negative NBLs encouraged the withholding
      of antibiotics, or detection of alternative pathology. We propose routine
      bacteriological lung surveillance of mechanically ventilated patients using this
      simple, inexpensive and safe technique.

PMID- 8255962
TI  - Managing severe alcoholic hepatitis complicated by renal failure.
AB  - We examined the management and outcome of 15 patients admitted consecutively to a
      specialist Liver Unit with severe alcoholic hepatitis complicated by renal
      failure. Fourteen patients were managed conservatively. Of these, 11/14 underwent
      renal dialysis for a mean of 24 days. Three patients, including two requiring
      dialysis, recovered renal function. Despite intensive care, 12/14 patients died.
      Death was frequently associated with bacterial and fungal sepsis. One patient
      underwent liver transplantation with prompt post-operative recovery of renal
      function. He was discharged from hospital 16 days later, and remains abstinent
      from alcohol with normal liver function after one year. Most patients with renal
      failure complicating severe alcoholic hepatitis will die, despite intensive care
      including renal dialysis. Selected patients may be suitable for liver
      transplantation.

PMID- 8255963
TI  - Smoking and mitochondrial function: a model for environmental toxins.
AB  - Defects of the human mitochondrial respiratory chain have been associated with
      several diseases including, most recently, certain neurodegenerative disorders.
      Several studies have used platelet mitochondrial function as a means to determine
      the potential contribution of respiratory chain defects to the pathogenesis of
      Parkinson's disease. Platelet biochemistry is subject to modulation by numerous
      factors that may circulate in the blood, including environmental agents, some of
      which may be relevant to mitochondrial dysfunction and neuronal toxicity. We
      measured mitochondrial respiratory chain enzyme activities in platelets from 18
      normal healthy non-smoking controls and compared them with those from 23
      similarly healthy cigarette smoking individuals. A 24% decrease (p < 0.02) was
      observed in the mean NADH CoQ1 reductase (complex I) activity of the smoking
      group compared with that of the non-smoking group. There was no significant
      change in the activity of any of the other respiratory chain enzymes. This is the
      first demonstration in vivo of mitochondrial inhibition by a common environmental
      agent. The results offer a novel mechanism of action for the cellular toxicity,
      or even mutagenicity, associated with cigarette smoking. In addition, these data
      have important implications for the interpretation of platelet mitochondrial
      complex I activities in disease states. They are particularly relevant to our
      interpretation and understanding of the complex I deficiency in Parkinson's
      disease platelets.

PMID- 8255964
TI  - Hydrocarbon exposure and tubular damage: additional factors in the progression of
      renal failure in primary glomerulonephritis.
AB  - To investigate the role of hydrocarbon exposure in the progression of
      glomerulonephritis, 68 patients (12 female) with biopsy-proven primary
      glomerulonephritis (60 proliferative cases, 8 membranous) were blindly assessed
      for chronic hydrocarbon exposure by a validated questionnaire. Serum creatinine,
      proteinuria, and urinary excretion of markers of renal tubular damage were
      measured. Patients were assessed for evidence of progressive renal failure (PRF)
      (defined as persistent rise of serum creatinine > 50 mumol/l above the baseline)
      during a mean follow up period of 5 years. Patients were divided according to the
      presence or absence of PRF, (group 1, n = 29, with PRF) and (group 2, n = 39,
      without PRF). The two groups were comparable in age, sex, duration of diagnosis
      (since the time of biopsy) and blood pressure control. The derived chronic
      hydrocarbon exposure scores were significantly higher in group 1 than 2 (p <
      0.001). Moreover, hydrocarbon exposure score since the diagnosis of
      glomerulonephritis was significantly higher in group 1 than 2 (p < 0.001). In
      group 1, 73% of patients continued to be exposed to hydrocarbons at their work
      site after the diagnosis of glomerulonephritis, compared to only 13% in group 2
      (p < 0.001). At renal biopsy, group 1 had a significantly higher mean serum
      creatinine than group 2 but the degree of proteinuria and proportion of patients
      with hypertension were similar. During follow-up serum creatinine rose
      significantly in group 1 but not in group 2. In group 2, proteinuria fell
      significantly during follow-up but remained unchanged in group 1. A higher
      proportion of patients from group 1 developed hypertension requiring
      antihypertensive drugs (84% vs. 28%; p < 0.001). Urinary marker secretion data
      indicated a possible association between tubular damage and renal impairment.
      These results suggest that chronic hydrocarbon exposure and renal tubular damage
      are important additional risk factors in the progression of primary
      glomerulonephritis.

PMID- 8255965
TI  - A study of acute community-acquired pneumonia, including details of cardiac
      changes.
AB  - We prospectively studied 102 patients, aged 15-50 years, with acute community
      acquired lobar pneumonia without underlying cardiorespiratory illness, admitted
      to Baragwanath Hospital May 1990-April 1991. Demographic, clinical,
      microbiological and laboratory data and negative prognostic features of these
      patients are described. In particular, we documented electrocardiographic changes
      and studied their possible relevance in patients with pneumonia.
      Electrocardiographic changes occurred in 32 patients (31%). The commonest changes
      were clockwise rotation (16%), followed by P. pulmonale (9.8%) and S1 Q3 T3
      pattern (7.8%) Other changes included right axis deviation (n = 6), right bundle
      branch block (n = 3), ventricular extrasystoles (n = 2), atrial fibrillation (n =
      1) and nodal rhythm (n = 1). These changes returned to normal in survivors after
      a mean of 2 days. The S1 Q3 T3 pattern was associated with cardiac enzyme leak
      (CK-MB fraction), hypoxia and a high Simplified Acute Physiology Score (SAPS). In
      addition, P. pulmonale, right axis deviation and clockwise rotation correlated
      with hypoxia and a high SAPS score. Clockwise rotation also correlated with serum
      (including cardiac fraction) enzymes leak (LDH and CK-MB fraction), and pulmonary
      artery pressure. The overall mortality rate was 10.8%, with no association
      between electrocardiographic changes and mortality. The negative prognostic
      factors documented were hypoxia (p < 0.0001), multilobar pulmonary consolidation
      (p < 0.0001), tachycardia (p = 0.0001), tachypnoea (p = 0.0002), renal
      dysfunction function (p = 0.0009), hypotension (systolic p < 0.02, diastolic p <
      0.003), bacteraemia (p = 0.003), and serum (including cardiac fraction) enzymes
      leak: LDH (p < 0.02), CK (p < 0.002) and CK-MB fraction (p = 0.0002). These
      factors, with the exception of renal dysfunction, also correlated with the need
      for intensive care unit admission. Acute and reversible electrocardiographic
      changes are common in acute community-acquired lobar pneumonia.
      Electrocardiographic changes, especially those compatible with acute cor
      pulmonale and accompanied by cardiac enzyme (CK-MB fraction) leak, correlated
      with severity of illness but not with mortality.

PMID- 8255966
TI  - Community screening for non-insulin-dependent diabetes mellitus: self-testing for
      post-prandial glycosuria.
AB  - Recent requirements of the GP contract have included the testing of random urine
      samples from all patients aged 16-75 years for glycosuria. As a means of
      detecting diabetes this will be both inefficient and wasteful of resources,
      because of the method employed and age group screened. We examined a simple
      method for screening large populations for non-insulin-dependent diabetes
      mellitus using self-testing for post-prandial glycosuria, and compared its
      performance to that using fasting plasma glucose and haemoglobin A1. The study
      involved five general practices, screening over 13,000 subjects aged between 45
      and 70 years. Of the 13,795 subjects screened, 10,348 responded (75%). Glycosuria
      was detected in 343 subjects (3.3%), of whom 330 (95.9%) attended for oral
      glucose tolerance testing. Of these 99 (30%) had newly diagnosed diabetes, 56
      (17%) had impaired glucose tolerance. A further 65 subjects were identified as
      having diabetes but were not on a register of cases. Prevalence of diabetes in
      this age group rose from 2.26% to 4.1%. In a normal population control group (442
      subjects from Ely), this system gave a sensitivity of 43%, specificity of 98% and
      positive predictive value of 53%, and compared favourably to the use of a fasting
      plasma glucose of 6 mmol/l, which gave a sensitivity of 65%, but only a
      specificity of 64% and positive predictive value of 9%. These results support the
      use of this simple system in large population screening for diabetes.

PMID- 8255967
TI  - Hyperhomocysteinaemia: a metabolic risk factor for coronary heart disease
      determined by both genetic and environmental influences?

PMID- 8255968
TI  - Management of paroxysmal atrial fibrillation.

PMID- 8255969
TI  - Inhaled nitric oxide: a magic bullet?

PMID- 8255970
TI  - The thalassaemia syndromes.

PMID- 8255971
TI  - Adult-type Gaucher disease in children: genetics, clinical features and enzyme
      replacement therapy.
AB  - Clinical manifestations of type 1 (Adult) Gaucher disease usually start in
      childhood. However, most of the previously published data describe the features
      of this disorder in adults. We present the clinical and genetic characteristics
      of 34 children and adolescents with type 1 Gaucher disease evaluated in our
      clinic during the past two years. Patients were aged 2-18 years; 18 were boys and
      16 girls. The majority presented before the age of 10. Growth retardation
      appeared as a prominent feature, with 26% in or below the third percentile in
      weight, and 30% so in height, especially in the youngest age group (2-5 years).
      Anaemia and thrombocytopenia occurred in 80% and 60% of the children,
      respectively. Hepatosplenomegaly was noted in all the children; only 3 were
      splenectomized. Skeletal involvement was evident on X-rays in 90% of the
      patients, but only 50% complained of bone pains. Three patients had severe bone
      disease, with avascular necrosis of the hip joint. Mutation analysis at the DNA
      level revealed the 1226/1226 genotype in 12 (35%) patients and 1226/84GG in 13
      (38%). Correlation was found between the genotypes and the severity of the
      disease, including growth retardation. A positive response was documented in all
      9 patients who completed 12 months of the recently-introduced enzyme replacement
      therapy for Gaucher disease.

PMID- 8255972
TI  - Human mannose-binding protein gene is regulated by interleukins, dexamethasone
      and heat shock.
AB  - Mannose-binding protein (MBP) is a plasma protein synthesized by hepatocytes.
      MBP, a structural analogue of the complement component C1q, can activate
      complement via the classical pathway and plays an important role in host defence.
      Expression of the human MBP gene was studied using the human hepatoma cell line
      HuH-7. RNA extracted from HuH-7 cells was reverse-transcribed to cDNA, amplified
      by the polymerase chain reaction and analysed by Southern blot hybridization. MBP
      mRNA expression in HuH-7 cells was increased by interleukin-6 (IL-6),
      dexamethasone and heat shock, decreased by interleukin 1 (IL-1), and unaffected
      by interferon gamma (IFN gamma), tumour necrosis factor alpha (TNF alpha) and
      transforming growth factor beta (TGF beta). Gel shift assays demonstrated Sp-1
      binding sites in the 5' region of the gene, and formation of specific complexes
      between DNA and nuclear protein extracted from HuH-7 cells treated with IL-1 or
      IL-6. Human MBP is an acute-phase protein, and transcription of its gene is
      enhanced by IL-6, dexamethasone and heat shock but inhibited by IL-1. The actions
      of the cytokines appear to be mediated by specific transcription factors.

PMID- 8255973
TI  - Psychosocial outcome and use of medical resources in patients with chest pain and
      normal or near-normal coronary arteries: a long-term follow-up study.
AB  - Forty-six patients who were investigated in 1979-80 for chest pain, and found to
      have normal or insignificantly narrowed coronary arteries on coronary
      angiography, were followed up after a mean interval of 11.4 years. Patients were
      interviewed and given standardized questionnaires covering chest pain and other
      physical symptoms, psychiatric morbidity, and functional capacity. Medical
      records for the follow-up period were reviewed, as were death certificates and
      post-mortem reports, where appropriate. All patients (100%) were traced to death
      or their current address. Four had died (11.4 year survival rate 91%), one from
      ischaemic heart disease. Continuing chest pain was reported by 74%, and in 16
      patients (38%), chest pain was either frequent, severe or both. A poor outcome
      for chest pain was associated with other physical symptoms and increased
      psychiatric morbidity, which for the entire cohort was higher than at 1 year
      after angiography. Twenty-six patients (58%) had received further hospital
      treatment for chest pain, including, in six patients, further coronary
      angiography. Twenty-nine survivors (71%) were taking cardiac medication, 12 (29%)
      were unable to work for medical reasons, and levels of functional disability were
      similar to those found in patients with myocardial infarction or angina. This
      study confirms the findings of previous studies with shorter follow-up intervals.
      Mortality was low, but high levels of chest pain, psychological distress, and
      functional incapacity persisted long after angiography. Patients reported many
      physical symptoms other than chest pain, and had made heavy use of medical
      resources. For many patients, reassurance after angiography had been ineffective,
      and the prognosis was poor. Early identification and effective management of such
      patients could offer the NHS substantial savings.

PMID- 8255974
TI  - Do beta 3-adrenoceptors mediate metabolic responses to isoprenaline.
AB  - We investigated whether the putative beta 3-adrenoceptors mediated metabolic
      responses to isoprenaline. Seven normal volunteers received infusions of
      isoprenaline, a (beta 1, beta 2 and beta 3-agonist), at 0.5-3.0 micrograms/min.
      They were pretreated with either placebo, 25 mg atenolol (a selective beta 1
      antagonist), or 5, 20 and 80 mg nadolol (which blocks beta 1 and beta 2 but not
      beta 3-adrenoceptors). Isoprenaline markedly (30.6%) increased basal metabolic
      rate (BMR): this increase was significantly reduced by 25 mg atenolol but not by
      5 mg nadolol. Significant beta 2-blockade (from tremor data) occurred with 5 mg
      nadolol but not with 25 mg atenolol. This suggests that beta 1 but not beta 2
      adrenoceptors are involved in the mediating thermogenic effects of isoprenaline.
      However, the rise in BMR was not totally blocked even by 80 mg nadolol (9.5%),
      which produced complete beta 1/beta 2 blockade, as evidenced by the elimination
      of the chronotropic effect of isoprenaline. This implies that the thermogenic
      response has a non-beta 1/beta 2-mediated component. There were also significant
      increases in plasma free fatty acids, glycerol, glucose, insulin and lactate, but
      these were completely abolished by beta 1/beta 2 blockade. Overall, isoprenaline
      produced an increase in BMR which is only partly due to stimulation of beta 1
      adrenoceptors, and which is not associated with beta 1/beta 2-mediated effects on
      carbohydrate and fat metabolism. This suggests the possibility of thermogenic
      beta 3-adrenoceptors in man, although their location and role remain unknown.

PMID- 8255975
TI  - The relationship between serial measures of disease activity and outcome in
      rheumatoid arthritis.
AB  - Disease activity was measured annually over a median period of 7 years (range 5
      9) in a cohort of 127 patients with rheumatoid arthritis. The measurements were
      plotted, and the area under the resultant curve measured. The relationship of
      serial measures of disease activity (area under the curve) to outcome (measured
      radiologically, functionally and by global assessment) was investigated. A
      significant correlation was found between persistent disease activity and
      radiographic deterioration. Similar results were found for functional outcome, as
      measured by Steinbrocker grade, health assessment questionnaire score or global
      assessment (by analogue score). Single measures of disease activity did not
      predict outcome. Although imprecise, current methods of measuring disease
      activity in RA, if measured serially, are valuable in predicting outcome over a 5
      10 year period.

PMID- 8255976
TI  - Plasma potassium, serum magnesium and ventricular fibrillation: a prospective
      study.
AB  - Low plasma potassium and magnesium concentrations have been advanced as risk
      factors for ventricular fibrillation (VF). For potassium, this assertion is based
      almost exclusively on retrospective data; for magnesium the evidence shows an
      association with ventricular arrhythmias but no direct association with VF. We
      studied the relationship between these electrolytes and VF prospectively. Plasma
      potassium and serum magnesium concentrations were measured on admission to our
      coronary care unit. Drug therapy, time from onset of symptoms, ECG, enzyme
      changes and clinical status were all recorded. VF was confirmed by analysis of 24
      h monitoring tapes. Mean plasma potassium in the 21 patients with VF who had
      measurements prior to their arrhythmia was 3.49 +/- 0.54 mmol/l, lower than that
      of the 1165 patients without VF (mean K 3.88 +/- 0.57 mmol/l, p < 0.05). Plasma
      potassium concentrations in the 17 patients with myocardial infarction and VF
      were lower (mean 3.58 +/- 0.41 mmol/l) than in those without VF (n = 417, mean
      3.89 +/- 0.61 mmol/l) (p < 0.05). Mean serum magnesium in the 12 patients with
      VF, measured prior to their arrhythmia (all with myocardial infarction) was 0.80
      +/- 0.07 mmol/l, which was not different from the mean for patients without VF (n
      = 781, 0.82 +/- 0.09 mmol/l) or from the mean of 0.81 +/- 0.08 mmol/l for those
      with infarction but not VF (n = 331). Low plasma potassium concentrations are
      associated with increased risk of ventricular fibrillation, but low serum
      magnesium concentrations are not.

PMID- 8255977
TI  - Lactic acidosis and falciparum malaria.

PMID- 8255978
TI  - Links of the Association of Physicians with developing countries.

PMID- 8255979
TI  - RSNA index to imaging literature. Volumes 178-189(I), 1991-1993.

PMID- 8255980
TI  - Activity and excitatory amino acid receptors.
AB  - 1. In lower vertebrates, optic fibers form a highly ordered retinotopic
      projection to the contralateral midbrain. 2. The formation of fine retinotopy
      during development or regeneration requires patterned impulse activity in optic
      fibers. 3. The transmitter used by optic fibers is probably glutamate. 4.
      Blockade of NMDA receptors prevents the formation of fine retinotopy. 5. The
      available evidence leaves open several different interpretations for these NMDA
      effects.

PMID- 8255981
TI  - Asian/non-Asian transcultural tricyclic antidepressant psychopharmacology: a
      review.
AB  - 1. Transcultural psychopharmacology is a discipline that seeks to determine the
      relative importance of society, culture, environment, genetics, and biophysiology
      on the prescribing and metabolism of, and response to psychotherapeutic
      medications. 2. Studies and surveys comparing psychotropic medication use in
      Asian and non-Asian populations suggest that differences may exist in drug dosage
      requirements, plasma drug concentrations corresponding to therapeutic and toxic
      effects, and the incidence and severity of adverse drug reactions. 3. This paper
      reviews and critiques the published controlled studies on Asian/non-Asian
      transcultural tricyclic antidepressant psychopharmacology, provides guidelines
      for the use of psychotropic medications in Asian populations, and offers
      suggestions for future transcultural studies. 4. Anecdotal reports suggest that
      differences exist between Asian and non-Asian populations in the pharmacokinetics
      of tricyclic antidepressants. Controlled studies have not consistently supported
      this view. 5. Studies with larger sample sizes and more rigorous controls are
      needed to determine if such differences do, in fact, exist.

PMID- 8255982
TI  - Clinical overview on moclobemide.
AB  - 1. Moclobemide is a novel benzamide reversible inhibitor of monoamine oxidase A
      and has clinical efficacy in a wide spectrum of depressive illness including
      endogenous and non-endogenous depression, in younger adults and in the elderly.
      2. Comparisons have shown similar efficacy to all main classes of antidepressants
      and much greater tolerability and safety in overdose than tricyclic
      antidepressants. Clinically, it is neither sedative nor alerting. 3. There is no
      need for dietary restrictions for patients on moclobemide on a normal diet, and
      drug interactions are few and usually mild. Specific cautions are noted with
      pethidine and with selective serotonin re-uptake inhibitor antidepressants. 4.
      Moclobemide is a useful addition to the range of antidepressants in clinical
      practice.

PMID- 8255983
TI  - Investigations of the cellular immunity during depression and the free interval:
      evidence for an immune activation in affective psychosis.
AB  - 1. Results of investigations of the immune function in affective disorders are
      conflicting. Some authors described an immune suppression, others an immune
      activation in major depression. The authors performed a study of cellular
      immunity in the MDD subtype endogenous depression. 23 patients suffering from
      endogenous depression were investigated during the depressive state, the results
      were compared with a group of 14 patients during the free interval and 51 healthy
      controls. 2. The lymphocyte proliferation after incubation with diphtheria- and
      tetanus toxoid, mainly stimulating T-cells, was reduced but after incubation with
      an antigen-cocktail, stimulating both, T- and B-cells, was increased in patients
      during depression and during the free interval compared to controls. 3. The
      CD3(+)- and CD4(+)-cells were significantly enhanced in both groups of patients
      while the CD8(+)-cells showed no differences to the controls. The ratio CD4+/CD8+
      was increased in patients, too, as described in some autoimmune disorders. 4. The
      suppressor cell activity was significantly reduced in the PWM-assay and in the
      PHA-assay. The mixed lymphocyte culture showed a tendency to reduced suppressor
      cell activity as well. 5. The results point to an immune activation and to a
      disturbed control of the proliferative activity in affective psychosis. A T-cell
      related defect, not compensated by an increased number of CD3+- and CD4+ -cells
      is discussed. 6. From our point of view, the conflicting results of
      psychoneuroimmunological investigations in depressive disorders may be related to
      etiologically different subgroups of depression. The diagnostic category of MDD
      is possibly one of the traps in psychoneuroimmunology.

PMID- 8255984
TI  - A preliminary trial of ascorbic acid as supplemental therapy for autism.
AB  - 1. This study presents the results of a 30-week double-blind, placebo-controlled
      trial exploring the effectiveness of ascorbic acid (8g/70kg/day) as a
      supplemental pharmacological treatment for autistic children in residential
      treatment. 2. Residential school children (N = 18) were randomly assigned to
      either ascorbate-ascorbate-placebo treatment order group or ascorbate-placebo
      ascorbate treatment order group. Each treatment phase lasted 10 weeks and
      behaviors were rated weekly using the Ritvo-Freeman scale. 3. Significant group
      by phase interactions were found for total scores and also sensory motor scores
      indicating a reduction in symptom severity associated with the ascorbic acid
      treatment. 4. These results were consistent with a hypothesized dopaminergic
      mechanism of action of ascorbic acid.

PMID- 8255985
TI  - The relationship of clinical psychopathologic rating and cognitive factors to
      clinical dementia staging.
AB  - 1. Sixty-six patients were assessed by one of three physicians employing CERAD
      assessment and were staged by CDR criteria. 2. The same day, trained raters
      completed the Brief Psychiatric Rating Scale, the Cornell Scale for Depression in
      Dementia and the Mini-mental State Examination. 3. Clinician's Global Rating of
      the CDR is strongly related to the Mini-mental State Examination Score. 4. The
      CDR is insensitive to mild psychopathology in this population.

PMID- 8255986
TI  - Within-session changes in sensory gating assessed by P50 evoked potentials in
      normal subjects.
AB  - 1. The authors studied within-session changes in P50 suppression occurring in a
      group of 28 normal subjects. 2. A conditioning-testing paradigm was used with 120
      pairs of 110 Db peak intensity clicks. Clicks were of 0.04 msec duration, 500
      msec separation and delivered through headphones at 10 second intervals. 3. Mean
      P50 suppression ranged from 60.5% during the first 30 click pairs to -19.1%
      during the last 30 pairs, with an overall mean suppression of 25.4%. 4. The
      authors concluded that P50 suppression is a dynamic process in normal subjects,
      and that further work is necessary to elucidate the factors affecting P50
      suppression.

PMID- 8255987
TI  - Increased anti-Sm antibodies in schizophrenic patients and their families.
AB  - 1. Autoantibodies in the Sm complex have become a useful serologic aid in the
      diagnosis of systemic lupus erythematosus (SLE) and have rarely been observed in
      other diseases. 2. A subset of SLE patients have a variety of psychiatric
      abnormalities, including schizophrenia. 3. The authors have recently observed
      that schizophrenic patients have a high incidence of autoantibodies suggesting
      that autoimmune phenomena may play a role in the pathogenesis of this disease. 4.
      In the present study the authors investigated multicase families with
      schizophrenia for the presence of anti-Sm antibodies and showed that these
      autoantibodies are elevated both in patients and in their healthy relatives. 5.
      An autoimmune process may be involved in the pathology of schizophrenia.

PMID- 8255988
TI  - Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits.
AB  - 1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been
      studied in the rabbit. Subsequently we tested the neurophysiological and
      behavioural interactions between ondansetron and L-5-HTP induced serotonergic
      syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.)
      increase in the cortical power density spectrum, particularly in the range of the
      lowest frequencies bands. This effect is expression of cortical synchronization.
      3. The lowest and mild dose, but not the highest, failed to produce behavioural
      sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5
      HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural
      pattern characterized by a decrease of cortical power spectrum density and
      stereotyped movements. The EEGraphic effects were significantly suppressed by
      administration of mild and higher doses of ondansetron, while the behavioural
      effects were inhibited by all doses tested. 5. It is concluded that ondansetron
      acts with considerably efficacy on central nervous system. The administration of
      low and mild doses shows a singular dissociation between EEGraphic and
      behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by
      ondansetron suggests that this drug acts on behaviour only when there is an
      altered physiological pattern.

PMID- 8255989
TI  - Characteristics of inositol polyphosphate metabolism in cultured adrenal
      chromaffin cells.
AB  - 1. Nicotine, high K+ and maitotoxin caused the inositol polyphosphate
      accumulation concomitant with 45Ca2+ uptake. 2. Angiotensin II (Ang II) and ATP
      induced the inositol polyphosphate accumulation without 45Ca2+ uptake. 3.
      Nifedipine-treatment and Ca(2+)-deprivation inhibited the high K(+)-induced
      inositol polyphosphate accumulation but failed to inhibit the Ang II-induced
      inositol polyphosphate accumulation. 4. 12-O-tetradecanoylphorbol-13-acetate
      inhibited the Ang II-induced inositol polyphosphate accumulation but failed to
      inhibit the high K(+)-induced one. 5. These results suggest that the formation of
      inositol polyphosphates may be regulated by two mechanisms, i.e. Ca2+ uptake
      dependent mechanisms represented by high K+, and Ca2+ uptake-independent
      mechanisms represented by Ang II.

PMID- 8255990
TI  - Phenelzine produces subsensitivity to nicotine.
AB  - 1. The authors attempted to detect a possible effect of treatment with phenelzine
      on a physiological response to nicotine in the rat. 2. Positive findings in an
      animal model suggest the feasibility of more complicated experiments in animals
      and the possibility of studies involving human subjects. 3. Treatment of Sprague
      Dawley rats (n = 10) with phenelzine sulfate (15.0 mg/kg ip) every 48 hours for
      14 days was associated with a 73.3% decrease in the hypothermic response to
      nicotine. 4. Treatment with phenelzine did not enhance the rate of elimination of
      nicotine. 5. The authors discuss a possible relationship between changes in
      nicotinic mechanisms and the therapeutic actions of drugs used to treat affective
      illness.

PMID- 8255991
TI  - [Subsequent psychological effects].
AB  - In connection with the concept of temporality and psychic causality, the notion
      of deferred action plays a significant role in Freud's thinking. Early
      experiences, impressions and recollections are later revised in the light of new
      experience and thus subsequently given a meaning that they did not originally
      have. The author's main concern here is to show that psychoanalysis of such a
      strictly hermeneutic nature--regarding the past entirely in terms of the present
      and projecting a whole system of new meanings onto it which the patient finds
      immediately convincing--is unable to satisfy the rigorous scientific standards
      implicit in Freud's approach to causal explanation and will thus necessarily fail
      to identify the actual past causes of present illness. Kerz-Ruhling's article is
      a call for a more empirically oriented form of psychoanalysis de-potentiating
      empathy and understanding in counter-transference and reinstating the inductive
      method of establishing causes.

PMID- 8255992
TI  - [Psychoanalysis, adolescence and subsequent psychological effects].
AB  - Theories of the avant-garde in art aim at discovering new meanings in what appear
      to be securely established traditions. This approach also plays an important role
      in psychoanalysis, inquiring as it does into the human capacity for subsequently
      relating to the past in such a way as to create new traditions with a view to
      restructuring the present. Erdheim's contention is that this historical capacity
      is a product of the two-phase nature of human sexual development and comes to
      fruition in adolescence: "Adolescence is the avant-garde of the individual." With
      reference to three specific factors--male-female polarity, the meaning of
      aggression and omnipotence, antagonism between family and culture--the author
      traces the way in which this past-oriented and future-related structure takes
      shape in adolescence.

PMID- 8255993
TI  - [Two authors in search of persons. The relationship, the field, the history].
AB  - The story developing within the two-person field of the psychoanalytic situation
      is usually interpreted in terms of transference phenomena of body fantasies.
      Ferro, by contrast, elects a narratological approach. He traces the way in which
      micro-stories develop within the psychoanalytic field reflecting the unconscious
      psychic collaboration between the two participants. The point of analysis is
      creative narrative, not precise reconstruction. With reference to a number of
      actual cases, the author argues that in each psychoanalytic interview "persons"
      are created expressing the projective identifications taking place between the
      participants. The result is a story of the psychoanalytic couple in which sense
      impressions from early childhood assume a subsequent significance.

PMID- 8255994
TI  - [Understanding Freud. On an essay by Ilse Grubrich-Simitis].

PMID- 8255995
TI  - The justification for a surgical staging system in endometrial carcinoma.
AB  - Three hundred and one patients with endometrial carcinoma who were surgically
      staged and treated postoperatively with irradiation at the Fox Chase Cancer
      Center or the Hospital of the University of Pennsylvania were retrospectively
      substaged by the 1988 FIGO staging system. For pathological stage I endometrial
      carcinoma, FIGO substage (IA/IB vs. IC) in addition to depth by thirds (< or =
      2/3 vs. > 2/3), grade (1 or 2 vs. 3), age (< or = 60 vs. > 60), and type of
      postoperative irradiation (vaginal alone vs. external +/- vaginal) were
      predictive for 5-year cause-specific survival in univariate analysis. For all
      pathological stages, excluding IIIB and IV endometrial carcinoma, FIGO stage (I
      or II vs. III) in addition to depth by thirds (< or = 2/3 vs. > 2/3), grade (1 or
      2 vs. 3), age (< or = 60 vs. > 60), and type of postoperative irradiation
      (vaginal alone vs. external +/- vaginal) were predictive for 5-year cause
      specific survival in univariate analysis. Clinical stage (I vs. II or III) was
      not a significant predictor of outcome in univariate analysis. Multivariate
      analysis of the above factors revealed FIGO stage in addition to grade, age and
      depth by thirds to be independent predictors of outcome. In conclusion, the FIGO
      surgical staging system better predicts outcome compared with the prior clinical
      staging system, although the FIGO substaging needs refinement. Grade, age, and
      depth by thirds are equally important prognostic factors in addition to FIGO
      stage and can add to the predictive value of the current FIGO staging system.

PMID- 8255996
TI  - Re-irradiation tolerance of rat spinal cord to fractionated X-ray doses.
AB  - Experiments were performed to assess the re-irradiation fractionation sensitivity
      in the rat cervical spinal cord. Animals were given initially three daily
      fractions of 9 Gy representing 75% of tolerance at the ED50 level. After an
      interval of 20 weeks, they were re-irradiated with graded doses of X-ray in
      single, 2, 5, 10 and 20 daily fractions, or a single retreatment top-up dose of
      12.8 Gy (equivalent to 80% of retreatment tolerance) followed by doses in 1, 2,
      4, 10 and 20 daily fractions. The end-point was paralysis of the forelimbs
      secondary to white matter necrosis. Latent periods to paralysis ranged from 188
      to 245 days from initial irradiation, or from 48 to 105 days from re-irradiation.
      For a given fractionated retreatment schedule, shorter latent times were observed
      in animals re-irradiated to higher total doses. The re-irradiation ED50 values
      for single, 2, 5, 10 and 20 fractions were 14.0 (95% CI 13.3, 14.2), 20.5 (19.9,
      21.2), 29.1 (28.0, 30.1), 36.3 (35.1, 37.4) and 47.8 Gy (46.2, 48.3),
      respectively. For re-irradiations with a 12.8 Gy top-up dose followed by doses in
      single, 2, 4 and 20 fractions, the retreatment ED50 values excluding the 12.8 Gy
      top-up dose were 4.5 (95% CI 3.0, 5.4), 6.5 (5.6, 7.3), 7.0 (5.0, 8.1) and 10.9
      Gy (8.9, 12.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8255997
TI  - Nicotinamide and carbogen: major effect on the radiosensitivity of EMT6 and HRT18
      tumours.
AB  - The effect of nicotinamide and/or carbogen breathing on the response of EMT6 and
      HRT18 tumours, irradiated in vivo, was evaluated using an in vitro colony assay.
      In the single dose schedules, the most efficient treatment was carbogen plus
      nicotinamide compared to air breathing mice. In a fractionated regime carbogen
      plus nicotinamide increased also response to radiation.

PMID- 8255998
TI  - Pentoxifylline: its pharmacokinetics and ability to improve tumour perfusion and
      radiosensitivity in mice.
AB  - The pharmacokinetics of pentoxifylline and its three major metabolites were
      measured after intraperitoneal administration of 10 mg/g or 100 mg/kg of drug in
      C3H mice. Peak concentrations of pentoxifylline were approximately 10 and 100
      micrograms/ml, respectively, with elimination half-lives (+/- 2 SE) of 4.6 (4.2
      5.1) and 7.5 (7.2-7.9) min, respectively. Plasma concentrations of the
      pharmacologically active hydroxy metabolite were approximately one-tenth those of
      the parent compound. In vitro evidence of the ability of pentoxifylline to
      increase blood cell deformability indicates that concentrations of up to 30
      micrograms/ml can increase deformability of both red and white blood cells; doses
      between 5 mg/kg and 100 mg/kg were therefore tested 15 min after administration
      to test the effect of the drug on tumour and normal tissue perfusion, tumour
      radiosensitivity and renal function immediately after exposure to appropriate
      drug concentrations. Using 86Rb extraction, doses of 10-100 mg/kg pentoxifylline
      were shown to increase relative tumour perfusion of the RIF-1 tumour to 140-170%
      of control, with no effect in skin, muscle, kidney, liver or lung, but with
      similar increases in spleen perfusion; there was no significant effect in any
      tissue after 5 mg/kg. Using a clonogenic assay, this increased tumour perfusion
      was shown to be reflected in increased tumour radiosensitivity to 25 Gy 15 min
      after pentoxifylline, with the same dose threshold of 10 mg/kg, and similar lack
      of dose-dependence at higher doses; the response indicated reduction in hypoxic
      fraction by a factor of 2-3. Renal function, measured by [51Cr]EDTA and
      [125I]iodohippurate clearance was unaffected at doses up to 50 mg/kg, with a
      slight effect at 100 mg/kg. The data indicate that pentoxifylline is effective at
      increasing relative tumour perfusion, with minimal effects on other tissues, and
      this increase is reflected in improved radiosensitivity. The doses at which the
      drug is effective are compatible with the mechanism being modification of blood
      cell deformability. Pentoxifylline shows promise as a clinical radiosensitiser
      acting by direct increase in tumour oxygenation.

PMID- 8255999
TI  - Cell-cycle progression during continuous low dose rate irradiation of a human
      bladder carcinoma cell line.
AB  - At very low radiation dose rates, the proliferation of mammalian cells continues
      unaffected but as the dose rate is increased there comes a point at which it is
      interrupted. The dose rate at which this happens is often thought to be a
      significant factor in the effects of brachytherapy: it may determine the range
      from an implanted source at which cell-cycle redistribution and repopulation
      effects will occur. By means of mitotic counts and DNA flow cytometry, we have
      examined the dose rate effect in a human bladder carcinoma cell line (MGH-U1).
      Irradiation at dose rate 0.1 cGy/min had little or no effect on cell-cycle
      progression. Suppression of mitosis and arrest of cells in G2 was observed at 0.4
      cGy/min and above. Surprisingly, the duration of mitotic arrest showed little
      dose rate dependence; it was followed by an overshoot of cells in mitosis after
      24-39 h of irradiation. An even more pronounced overshoot of cells in G2 occurred
      and persisted throughout the irradiation period. The cell kinetic data indicate
      that after the temporary block in cell-cycle progression, cell proliferation
      continued at all dose rates up to 1.4 cGy/min. We have evaluated these results in
      the light of previous studies in this department of the dose rate effect for cell
      survival in the MGH-U1 cell line. After 24 h irradiation at 1.4 cGy/min the
      surviving fraction was below 10(-2), also after 30 h at 1.0 cGy/min. When cell
      cycle blockade is considerable, so is the level of cell killing. Flow-cytometric
      data therefore are dominated by the properties of cells that are doomed to
      die.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256000
TI  - Three-field isocentric breast irradiation using asymmetric jaws and a tilt board.
AB  - Perfect abutment of medial and lateral tangential breast portals with the
      adjacent supraclavicular field may be achieved with ease. A simple and safe
      approach was developed using a tilt board and new technology that is standard on
      a popular linear accelerator. The patient is secured on a tilt board as a means
      to level the chest wall. Isocenter is placed at depth on the matchline, where
      asymmetric jaws are used to produce non-divergent field edges and a perfect
      abutment. This is done without the need for table or collimator rotations, beam
      splitters, or vertical cephalad blocks. The dorsal beam edge of the tangents is
      made coplanar by rotating the gantry more than 180 degrees. This procedure
      produces a dosimetrically sharp field edge and eliminates concern about block
      transmission and excess dose to the contralateral breast. Set-up is fast, and the
      steps involved are simple and few. Advantages and limitations of this technique
      are presented.

PMID- 8256001
TI  - A 3-D radiosurgical methodology for complex arteriovenous malformations.
AB  - A 3-D methodology, the associated targets methodology, for planning radiosurgical
      irradiations of complex arteriovenous malformations (AVMs) is presented. It uses
      the ARTEMIS-3D treatment planning system and has been devised and adopted by our
      group since January 1990. Its main features are: (a) prescription and delivery of
      a minimal target dose on the surface of the lesion, corresponding to a 60-70%
      isodose range. The dose to adjacent functional neurological structures is taken
      into account as well as the maximum dose to the lesion; (b) An optimisation
      approach consisting of obtaining the optimal superimposition of the isodose
      surface and the 3-D contour of the lesion and sharp fall-offs by interactive
      manipulation of the treatment parameters. The clinical choice of the treatment
      plan is based on a compromise between the optimal reference isodose surface
      encompassing the lesion and the minimisation of the volumetric dose fall-off. In
      complex AVMs the angiographic results have been significantly improved in
      comparison with our previous experience because of the better achieved lesion
      encompassing.

PMID- 8256002
TI  - Stereotactic radiotherapy of irregular targets: a comparison between static
      conformal beams and non-coplanar arcs.
AB  - Stereotactic radiotherapy using a linear accelerator is usually equated with the
      technique of delivery using multiple non-coplanar arcs, which achieves a
      spherical dose distribution. As the majority of intracranial lesions are not
      spherical, a range of schematized tumour shapes were planned to assess the role
      of static conformal beams in the treatment of irregular lesions. A sphere and 2
      ellipsoids, ranging from 20 to 50 mm maximum diameter located intracranially were
      planned using 3, 4, and 6 non-coplanar static beams with conformal blocks and
      were compared with four 120 degree non-coplanar arcs. Comparison of the plans was
      made by the relative sparing of normal tissue outside the target volume using
      three-dimensional dose-volume distributions. Non-coplanar arcs spared more normal
      tissue at low isodoses and achieved the best high dose sparing for spherical
      targets. For the majority of irregular targets, 3 and 4 static beams spared more
      tissue at doses > or = 50% and > or = 80% than the arc technique. For all
      irregular volumes, maximum sparing of normal tissue to isodoses > or = 50% and >
      or = 80% of the treatment isodose was obtained with 6 static conformal beams. We
      conclude that irregularly shaped tumours suitable for stereotactic radiotherapy
      with a linear accelerator are better treated with conformal static non-coplanar
      beams rather than with the multiple arc technique.

PMID- 8256003
TI  - Feasibility of curative radiotherapy with a concomitant boost technique in 33
      patients with non-small cell lung cancer (NSCLC)
AB  - Thirty-three patients with an inoperable NSCLC were treated with a dose of 60
      Gy/20 fractions/25 days, using a concomitant boost technique. A dose of 40 Gy/2
      Gy/25 days was given to the tumor area and a part (15 patients) or the whole (18
      patients) mediastinum. During each session a simultaneous boost to the tumor of 1
      Gy was administered. Moderate acute oesophageal toxicity was observed in 7/33
      patients (22%). One out of 33 patients developed serious late oesophageal
      toxicity. A correlation between the oesophageal toxicity, absorbed oesophageal
      dose of irradiation and length of the elective field was observed. Five out of 33
      patients developed subacute radiation pneumonitis grade 2 or 3. In selected
      patients with inoperable NSCLC radiotherapy, with a dose of 60 Gy/20 fractions/25
      days, using a concomitant technique is feasible.

PMID- 8256004
TI  - Esophageal ulceration following high-dose-rate intraluminal brachytherapy for
      esophageal cancer.
AB  - Prophylaxis of esophageal ulceration was studied in 78 esophageal carcinoma
      patients after high-dose-rate intraluminal brachytherapy. Before the standard
      treatment regimen of radiotherapy was established, 15/17 patients developed
      ulcers. This decreased to 19/38 with the standard treatment regimen, and to 9/23
      when antiulcer therapy was added (p < 0.01).

PMID- 8256005
TI  - [Angiotensin converting enzyme and sarcoidosis].

PMID- 8256007
TI  - [Tuberculosis in 1991. A hospital based study].
AB  - A retrospective clinical, epidemiological study was carried out with the 53 cases
      of tuberculosis diagnosed in our center during 1991. The incidence rate was 4.4
      per 1,000 clinical histories. Fifteen patients (28.3%) were HIV+, and five were
      marginalized illegal immigrants (9.4%). Seventy-three percent of the HIV+
      patients and 42% of the HIV- patients presented extrapulmonary involvement. In
      hospital mortality was 20% in HIV+ patients and 2.6% among the remainder.

PMID- 8256006
TI  - [Elevated negative predictive value of angiotensin converting enzyme in the
      diagnosis of active sarcoidosis].
AB  - OBJECTIVE: To evaluate the usefulness of angiotensin converting enzyme (ACE) in
      the differential diagnosis of active sarcoidosis in action with other
      interstitial and granulomatous processes. METHODS: The study involved 30 patients
      with a histological diagnosis of sarcoidosis, 38 subjects with
      anatomopathologically and/or microbiologically confirmed pleuropulmonary
      tuberculosis, and 12 subjects with idiopathic pulmonary fibrosis confirmed by
      histological studies. Following the technique developed by Rohatgi and Ryan, a
      radioenzymatic system was used to determine the activity of serum ACE. In
      patients with sarcoidosis, levels of ACE were measured in active cases as well as
      those in remission. Our laboratory reference values for those over 20 years of
      age are 39.84 +/- 9.19 mumol/min/l. RESULTS: Levels of ACE were significantly
      higher (p < 0.001) in active sarcoidosis (67.71 +/- 17.73 mumol/min/l) than
      during inactivity (41.18 +/- 16.00 mumol/min/l), tuberculosis (46.99 +/- 13.65
      mumol/min/l), or fibrosis (35.87 +/- 11.36 mumol/mol/l). A cut-off point of 59
      mumol/min/l shows a significant association with the diagnosis of active
      sarcoidosis (p < 0.001) and reaches a negative predictive value of 90.90%.
      CONCLUSION: The usefulness of serum ACE in the differential diagnosis of
      sarcoidosis should be reconsidered.

PMID- 8256008
TI  - [Heparinoids versus nitroglycerin in the treatment of superficial phlebitis].
AB  - The purpose of this study was to evaluate the beneficial effects of transdermal
      nitroglycerine (TNG) in the treatment of superficial phlebitis caused by
      endovenous catheters and to compare them with the effects from the application of
      heparinoid substances. The study performed was prospective, randomized during a
      six-day period. One hundred patients (73 male and 27 female), aged 28-89 years
      (mean 67.3), participated in the study; all presented phlebitis, diagnosed by the
      presence of pain, erythema, edema, and fibrous cord in the area around the
      catheter. Among 50 subjects, two cm of NTG gel were administered to the affected
      zone once a day, and for the other 50 subjects, heparinoid substances were
      applied three times a day. The value parameters were: time for the disappearance
      of pain and time for reducing erythema, edema, and fibrous cord in half (all
      measured in hours). We found significant differences between the two treatments
      with TNG yielding greater improvement in terms of disappearance of pain (TNG:
      50.2 +/- 39.7, heparinoids: 72.0 +/- 39.9), time for reducing erythema in half
      (TNG: 28.0 +/- 24.2, heparinoids: 54.6 +/- 34.5), and time for reducing fibrous
      cord in half (TNG: 58.3 +/- 38.4, heparinoids: 84.5 +/- 41.5). Edema was reduce
      before with TNG; however, this difference was not significant (TNG: 31.2 +/-
      20.3, heparinoids: 33.0 +/- 25.7). We conclude that transcutaneous TNG should be
      applied systematically in patients with superficial phlebitis, given that it is
      more effective than the usual treatment with heparinoid substances.

PMID- 8256009
TI  - [Cranio-encephalitic manifestations in neurofibromatosis. A study with magnetic
      resonance and computed tomography].
AB  - We present the cranioencephalitic alterations of twelve patients with
      neurofibromatosis (eleven type 1 and one type 2) we studied using both computed
      tomography (CT) and magnetic resonance (MR). In addition, we made a comparison of
      the two techniques. MR allows greater differentiation of gliomas, neurinomas, and
      neurofibromas and better characterizes tumoral vascularization. Lesions
      undetected by CT can be identified, and it is a non-invasive method. For these
      reasons, we consider MR the technique of choice in the study of
      neurofibromatosis, even though CT continues to be superior in examining osteal
      dysplasias and calcifications and should thus be used as a complementary
      technique for an exact assessment of the lesions.

PMID- 8256010
TI  - [Pyogenic sacroiliitis. Presentation of 10 cases].
AB  - We report the clinical, radiological and microbiological features of ten patients
      diagnosed of pyogenic sacroiliitis in an Internal Medicine Department during a 13
      years period. Clinical signs and radiological or scintigraphical findings were
      present in every case. Staphylococcus aureus was isolated in blood cultures in
      eight cases. We remark mean age (26.2 years), male predominance and the high
      prevalence of intravenous drug abuse as the main epidemiological data in our
      patients. Onset was acute in 60% of the cases, and subacute in the others.
      Erythrocyte sedimentation rate and a high white blood cell count were uniformly
      elevated among laboratory tests. Initial roentgenograms were normal in 60%. Bone
      scans were the most sensitive diagnostic aid. All the patients were treated with
      intravenous cloxacilin between two and eight weeks; aminoglycosides were added in
      four patients. We have observed two cases of psoas abscesses that required
      surgical drainage.

PMID- 8256011
TI  - [Pulmonary carcinoma associated with bullous emphysema].
AB  - Malignant complication of pulmonary bullous disease is rare but not negligible.
      Its importance lies in the young age when it appears. Eighty-nine cases in the
      literature, including four of our own cases, are included in this review.
      Etiopathogenic theories are discussed along with clinical, radiological,
      pathological, diagnostic, prognostic, and treatment characteristics. Smoking is a
      primary factor in this process, and quitting is key in terms of prevention.
      Surgical methods are usually necessary to perform the diagnosis, but that does
      not exclude the use of other techniques-particularly, fine-needle aspiration
      biopsy under radiological control-whose role should be validated. The prognosis
      is bad if there is no commitment to prevention. Even though the value of serial
      radiological controls is unknown, such controls may help in the early detection
      of neoplastic degeneration in bullous disease. The nature of the problem in
      handling these cases therapeutically is determined by the severity of bullous
      dystrophy: therefore, surgery should be considered on an individual basis.

PMID- 8256012
TI  - [Treatment of aggressive and high-grade lymphomas].

PMID- 8256013
TI  - [Nutrition and mental function in the elderly].
AB  - A deterioration in cognitive functions is characteristic of the ageing process
      and is one of the principle causes for disability in old age. It is possible that
      some of the neuropsychiatric alterations associated with old age may be due to
      certain subclinical vitamin deficiencies and, as such, may be corrected in some
      cases with adequate nutrition. This article presents a broad review of the
      various research efforts published on the subject.

PMID- 8256014
TI  - [Influence of nutritional status on the organism's response to infectious
      disease].
AB  - The nutritional status of a patient determines to a great extent his/her
      susceptibility and capacity in responding to infections. Protein and caloric
      malnutrition as well as many selective mineral and vitamin deficiencies
      deteriorate the immune and inflammatory metabolic response, increasing the
      frequency of infections and worsening their evolution and prognosis. Furthermore,
      recurrent infections can deteriorate nutritional status, with both problems
      forming a vicious circle that needs to be recognized for adequate treatment. This
      problem is not as foreign to us as we might think, given that many hospitalized
      patients as well as those with chronic diseases suffer from serious nutritional
      deficiencies. If we also take into account the proposition that the nutritional
      status of a patient can affect his/her response to treatment with antibiotics and
      vaccines, we realize then that not enough attention has been paid to this
      important public health risk factor to date.

PMID- 8256015
TI  - [Effects of n-3 polyunsaturated fatty acids on the cardiovascular system. Should
      their use be recommended?].
AB  - The effects of n-3 polyunsaturated fatty acid (n-3 PFA) intake on lipoprotein
      metabolism, eicosanoid metabolism, coagulation and the fibrinolytic system,
      mediators of inflammation, and blood pressure are discussed. The possible role
      such effects may have on the process of atherogenesis is examined. Laboratory
      animal studies with n-3 PFA supplements are reviewed. Finally, a review of
      clinical and epidemiological studies in human subjects is made in order to
      evaluate whether the experimental findings have clinical relevance. The
      conclusion is that, at the present time, there is insufficient support for the
      use of n-3 PFA supplements either in prophylaxis or in treating ischemic
      cardiopathy.

PMID- 8256016
TI  - [Recurrent hypotension and cutaneous lesions].

PMID- 8256017
TI  - [Splenomegaly and obstructive uropathy].

PMID- 8256018
TI  - [Intoxication by methanol: meta-analysis of 37 cases].

PMID- 8256019
TI  - [Hypoglycemia secondary to intravenous pentamidine treatment without subsequent
      diabetes mellitus].

PMID- 8256020
TI  - [Cholestasis in a woman taking oral contraceptives: occasionally it is necessary
      to rule out associated extrahepatic biliary pathology].

PMID- 8256021
TI  - [Polyneuropathy from sniffing glue].

PMID- 8256022
TI  - [Osteoarthritis due to Coxiella burnetii].

PMID- 8256023
TI  - [Ventilation accessories at home].

PMID- 8256024
TI  - [Atmospheric pollution and asthma].

PMID- 8256025
TI  - [Does sleep apnea syndrome merit treatment with continuous positive pressure?].

PMID- 8256026
TI  - [Chronic respiratory insufficiency. Non-invasive long-term ventilation methods].
AB  - The techniques of non-invasive ventilation have reappeared in force as an
      assortment of therapeutic techniques since the end of the 1980's. At the same
      time there was a transient renewed interest in perithoracic ventilation favouring
      the use of new methods of connection to the patient (e.g. poncho). The principal
      feature has been the use of intermittent positive pressure ventilation by the
      nasal route, which rapidly became essential for home therapy in patients with
      chronic restrictive respiratory failure notably in those secondary to thoracic
      deformation and to neuromuscular pathology. The concept of resting the
      respiratory muscles has been the basis for techniques of ventilatory assistance
      and in part the nasal route has now replaced home ventilation using a
      tracheotomy. Also in certain types of acute respiratory failure, nasal
      ventilation widely preferred over endotracheal ventilation.

PMID- 8256027
TI  - [The role of radiotherapy in bronchopulmonary cancer].
AB  - Pulmonary cancer is a major problem as much in terms of public health as for
      treatment. Radiotherapy plays an important therapeutic role. For a long time it
      has been used to treat inoperable tumours and for palliation, none the less in
      certain clinical situations it can be used as an alternative cure: in that case
      it's most often integrated with surgery and-or chemotherapy. Modern techniques of
      localization and of planning treatment have been briefly reviewed. In small cell
      cancer the survival is improved, as well as local control by thoracic
      irradiation. Current research has produced new knowledge in radiobiology which is
      opening up new therapeutic possibilities in the treatment of this disease.
      Various schemas for fractionating the radiotherapy and its sophisticated
      integration with chemotherapy have enable notable progress. Non-small cell
      bronchial cancer presents a particular challenge on account of its relative
      insensitivity to chemotherapy. Treatment is based on surgery and radiotherapy.
      Radiotherapy is a useful alternative to surgery for those patients who are
      inoperable on account of poor respiratory function. For cancer which has advanced
      locally new strategies of induction by associating radiotherapy and chemotherapy
      prior to surgery are under evaluation. Numerous cases of advanced disease are
      typically treated with radiotherapy alone. New schemas for hyperfractioning are
      giving rise to promising results and are clearly beneficial in combination with
      other therapeutic approaches. The side effects of thoracic irradiation can be
      controlled; the most serious can be prevented by careful attention to the volume
      treated and to the technique of irradiation. Radiotherapy offers an effective
      alternative and has a good cost effective relationship for the palliative
      treatment of metastatic lesions. The optimal use of these local and systemic
      therapies would enable an improvement in the evolution of the disease in these
      patients with pulmonary cancer.

PMID- 8256028
TI  - [The epidemiology of asthma in the elderly. Apropos of a review of the
      literature].
AB  - Increased longevity and the maintenance of autonomy in the elderly has lead to an
      enlargement of the study of asthma beyond 65 years. If the majority of published
      work in the literature concludes there is an excess mortality in the elderly
      asthmatic one cannot exclude the possibility that this excess mortality is due to
      the association, at this age, of asthma with other respiratory problems. This
      association would also explain the great variations in prevalence reported by
      different authors, from 3 to 6% with notable differences according to the sex.
      Bronchial reactivity appears to be less linked to allergy after 65 than in the
      young subject. In the elderly asthmatic the frequency of a past history of
      allergy and of positive cutaneous tests are weaker than in the young, and there
      is little difference when compared to the non-asthmatic subject. On the other
      hand the majority of studies show that smoking, respiratory infections, and
      social class are particularly linked to asthma beyond the age of 65. Although the
      data on predictive factors may be rare and contradictory certain published works
      suggest that deterioration in respiratory function most often precedes the
      appearance of symptoms suggesting the diagnosis. Many uncertainties remain in
      relation to asthma in the elderly. This is because in large part there are
      insufficiently specific identifying criteria. There is a need to develop
      standardised methods of evaluating respiratory handicap, notably specific data on
      the quality of life as this would be indispensable in evaluating the consequence
      of asthma in the elderly subject.

PMID- 8256029
TI  - [Spontaneous pneumothorax. A comparison of thoracoscopy and thoracotomy].
AB  - The aims of this study were to assess the advantages of surgical thoracoscopy
      versus thoracotomy. Two 16-patient groups (thoracotomy, thoracoscopy) were
      compared. They were equivalent with regards to technique, age, etiology and lung
      dystrophy. Patients were called by phone to evaluate the surgical and functional
      results. The questionnaire was filled out by an independent physician who ignored
      the surgical technique used. Hospital stay was 7 +/- 2 days for thoracoscopy
      versus 11.5 +/- 5 days for thoracotomy (p < 0.003). During the J30 to J60 period
      of time, pain was mild in 94% of thoracoscopy cases and severe or unbearable in
      69% of thoracotomy cases (p < 0.002). Mobility of the shoulder was fully
      recovered in all thoracoscopy patients within the first month versus only 62% of
      recovery at 3 months in the thoracotomy group (p < 0.0001). Working was possible
      at 1 +/- 0.8 month in the thoracoscopy group versus 2.6 +/- 0.8 months in the
      thoracotomy group (p < 0.002). Leisure activities were resumed at 2 +/- 1 month
      in the thoracoscopy group versus 4 +/- 1 months in the thoracotomy group (p <
      0.0005). Only one relapse occurred in the thoracoscopy group. Thoracoscopy
      prevents the drawbacks of thoracotomy but keeps the same efficiency in the
      treatment of pneumothorax.

PMID- 8256030
TI  - [A trial comparing artificial noses and heat exchangers during assisted
      ventilation using tracheotomy at home. CARDIF. The Committee of the Organization
      of Respiratory Assistance of the Ile-de-France].
AB  - Thirteen patients with a tracheostomy who were undergoing artificial ventilation
      at home were included in a study covering 62 episodes, during a month of
      treatment, which was undertaken with three different humidification systems: A
      Puritan Bennet Cascade humidifier (C), a Swedish nose Vygon-(V) (a hydroscopic
      condenser humidifier) and a Pall filter (P). Five patients abandoned the study
      because of discomfort with C (1), P (2), or V (2). The discomfort described by
      three patients was identical with the three systems used during ventilation. The
      two systems using the artificial heat humidification exchanger were considered
      more simple to use than the Cascade for the patients. Using the system for three
      years for a patient who was being ventilated for 12 hours out of 24 showed the
      increasing cost ranging from the Vygon nose, to the Cascade and finally to the
      Pall filter. The percentage of time spent on antibiotics was identical with the
      three systems (11% of the time). A bacteriological study showed that only the
      Pall filter permitted the respirator tubes to be kept sterile. The most polluted
      circuit from the bacteriological point of view was that used with the Cascade. In
      conclusion, when it was compared to the humidifier Cascade the two artificial
      noses appeared as simple to use and the Pall filter was the safest
      bacteriologically.

PMID- 8256031
TI  - [Clinical and economic evaluation of the initial assessment of small cell cancer
      of the lung. Alternatives to classic evaluation. LGTO. The Lyon Group of Thoracic
      Oncology].
AB  - Alternatively to the usual evaluation summary, a characteristic of small cell
      lung cancer, is the probability of significant diffuse metastases; the prognosis
      is directly linked to the extent of these metastases. Moreover, the assessment of
      the initial extension becomes heavier and more costly as investigations continue
      and each new technology appears. In order to evaluate the contribution of each
      examination, a classification has been established as a function of the time
      scale to obtain the results, of the technology involved, or whether the
      investigation is painful or not and any likelihood of iatrogenic side-effects. An
      assessment in three stages is proposed to achieve the most effective and cheapest
      diagnosis possible. In relation to the usual technique of assessment this
      sequential approach allows for a 27% reduction in the time-scale for the
      diagnosis of diffuse disease, 51.3% in terms of technical involvement, 46.3% in
      terms of pain and discomfort and 53.9% in terms of iatrogenic potential. At the
      same time a reduction in cost of 47.5% is observed.

PMID- 8256032
TI  - [Unrecognized occupational risk of pleural mesothelioma. The example of the Rhone
      Alps region].
AB  - A retrospective study of pleural mesothelioma diagnosed between 1980 and 1988 in
      the Rhone-Alpes region allowed to identify 224 cases. From the 187 patients in
      which occupational history was available 105 (56%) had been exposed to asbestos
      at work and 44 had been recognised as occupation disease and compensated. These
      data illustrate that the real incidence of the disease is largely underestimated
      and that legal procedure for occupational disease recognition is highly
      deficient.

PMID- 8256033
TI  - [Clinical data and descriptive epidemiology of primary bronchial cancer. 9 years
      of activity of the Isere Registry].
AB  - Systematical registration of morbidity for lung carcinoma of the primary type was
      performed since January 1979 for the department of Isere, where a population of
      940,000 inhabitants are living. Results for nine years registration (1979-1987)
      are dealing with 2,590 new cases. Crude incidence for primary lung carcinoma is
      55.7 per 100,000 among men, and 5.9 for women (sex ratio: 11.7). Upper lobe is
      the site more concerned. There is no preference as regard laterality. When
      lymphatic nodes are explored (32%), there is an extension of the carcinoma for
      75.2% of them. At the moment of the diagnostic, there is already a metastasis for
      24% of the patients, mainly for bones. Among men and women, proportions for the
      squamous cell type are respectively 52.6% and 22.3% (60.8% and 28.7% of
      histologically identified cases), for the small cell type: 18.4% and 16.3% (21.2%
      and 21.0% of histologically identified cases), and for glandular carcinomas:
      13.2% and 32.1% (11.9% and 41.5% of histologically identified cases). Results of
      the pathological examination are known in 92.8% for primary lung carcinoma cases.
      As regard first course treatment, surgery is performed in 34.9% of the cases,
      radiotherapy in 60.4%, and chemotherapy in 32.2%. Fairly high incidence of lung
      carcinoma in man in Isere, contrasts with rather low incidence in woman, a
      situation rather different that the one in England and North America, where
      figures for women are slowly gaining over the one's for men.

PMID- 8256034
TI  - [Thymoma and primary Gougerot-Sjogren syndrome progressing to severe
      bronchiolitis].
AB  - The authors report a case of a thymoma associated with Gougerot-Sjogren's
      syndrome in a patient aged 40 years. The excision of the thymic tumour and
      complementary radiotherapy lead to a remission in the patient. There was an
      unfavourable progression of this syndrome from a respiratory stand-point with the
      development of a predominantly bronchiolitic picture over four years.

PMID- 8256035
TI  - [Bronchiolo-alveolar carcinoma complicating myasthenia treated by azathioprine].
AB  - We report a case of broncho-alveolar carcinoma (CBA) in a man of 64 who had been
      treated with azathioprine for severe myasthenia gravis. The myasthenia was
      characterized by predominant involvement of the respiratory muscles, by
      resistance to anticholinesterase and by association with a thymoma without
      improvement after thymectomy. The CBA was associated with alveolar haemorrhage
      (HA) confirmed by lung biopsy and also by an infection due to Mycobacterium
      chelonae. The occurrence of HA in an immunodepressed patient is often due to an
      infection, notably aspergillosis. The role of CBA and the mycobacterial
      infections in the pathogenesis of HA is discussed. The use of azathioprine may
      lead to the occurrence of cancers, notably lung cancers, and also to haemopoietic
      neoplasia when doses of greater than 50 grams are used. We think that
      azathioprine may have contributed to the genesis of CBA in our patients.

PMID- 8256036
TI  - [Fistulous pulmonary abscess in the bronchi detected by staphylococcal
      spondylodiscitis, with the presence of bony sequestra in the bronchial
      secretions].
AB  - The authors report the case of a man aged 70 who was admitted to hospital for
      staphylococcal pulmonary suppuration which occurred during the long-term follow
      up for an osteosynthesis for a fractured humerus. The diagnosis of a pulmonary
      abscess in contiguity with a staphylococcal spondylodiscitis was only established
      by computed tomographic examination and the aspiration from a vertebral body. The
      outcome was fatal, despite appropriate antibiotic treatment, on account of the
      past medical history of the patient. The diagnosis might have been made by the
      presence of osseous sequestra in the bronchial secretions, the bronchial fistulae
      in contiguity with the vertebral column was confirmed at autopsy.

PMID- 8256037
TI  - [Chylomediastinum after mediastinoscopy. Apropos of a case].
AB  - A mediastinal chylous effusion occurred in a young woman after a mediastinoscopy.
      This effusion healed rapidly with medical treatment. An understanding of the
      anatomy of these intra-thoracic/lymphatic channels explains that intra-thoracic
      chylous effusions may occur in case of incontinence of the lymphatic vessels
      which connect the tracheo-bronchial nodes to the thoracic duct in the
      mediastinum. This is very important following the surgical excision of a node
      because incontinent lymphatic vessels are directly sectioned. When the lymph
      nodes are biopsied in an enclosed cavity such as the mediastinum, the quantity of
      lymphoid tissue acts as an obstacle to reflux of the lymph which is thus less
      significant and more easily controlled.

PMID- 8256038
TI  - [Mercury pulmonary embolism after voluntary injection].
AB  - We describe a case of pulmonary emboli due to mercury in a female drug addict who
      was HIV positive and had voluntarily injected herself with mercury. The diagnosis
      was guided by the history and by the characteristics of the chest radiograph and
      was confirmed by blood and urine levels of mercury and the radiograph taken of
      the site of the intravenous injection. Three years after the injection the
      patient did not reveal any signs suggesting disturbance due to the chronic
      pulmonary exposure to mercury, but there was a reduced carbon monoxide transfer,
      whose interpretation was difficult due to the past respiratory history and to the
      drug addiction.

PMID- 8256039
TI  - [Acquired hypogammaglobulinemia and multifocal granulomatosis].
AB  - In adult acquired hypogammaglobulinaemia multi focal granulomas have often been
      described and have regularly led to the hypothesis of an association with
      sarcoidosis. We present a case of this type in a man aged 29 who was a smoker
      with a hypoglobulinaemia involving IgG, IgA and IgM and which was discovered
      following pneumococcal pneumonias. He presented with a significant
      hepatosplenomegaly and absent cutaneous reactions to T dependent antigens with an
      elevated ACE activity. Histological examination of the splenectomy specimen and
      of the liver biopsy showed an infiltration by epithelioid follicles and confluent
      giant cells without necrosis. The pulmonary studies showed a normal chest
      radiograph but the bronchial biopsy again found a granulomatous infiltration. The
      broncho-alveolar lavage was cytologically normal and a very slight and
      paradoxical reduction of the alveolar immunoglobulins was noted implying either
      an active intra-alveolar concentration of immunoglobulins or a local synthesis.
      In the light of the few reported cases it seems that the diagnosis of sarcoidosis
      should be dismissed here in favour of multi focal granulomatosis with
      hypogammaglobulinaemia. In hypogammaglobulinaemia there is no clinical or
      biological method (IDR tuberculin, ACE, Kveim, histology) to confirm a superadded
      diagnosis of sarcoidosis.

PMID- 8256040
TI  - [A pleural tumor disclosing a non-Hodgkin's lymphoma: the value of thoracoscopy].

PMID- 8256041
TI  - [Thoracic opacity and standard pulmonary radiography].

PMID- 8256042
TI  - [Need for large sample size in clinical trial and statistical analysis of data
      from the trials].

PMID- 8256043
TI  - [Coronary thrombolysis].

PMID- 8256044
TI  - [Antiarrhythmic drugs].

PMID- 8256045
TI  - [Antihypertensive drugs and prevention of myocardial infarction].

PMID- 8256046
TI  - [The prevention of stroke in atrial fibrillation].

PMID- 8256047
TI  - [Study of suitable analyzed signal duration and criteria for abnormal signal
      averaged electrocardiogram on frequency-domain analysis in patients with
      Duchenne's muscular dystrophy].
AB  - We investigated the optimal condition to detect abnormalities on the fast-Fourier
      transformation of the signal-averaged electrocardiogram (SA-ECG) by studying the
      effects of analyzed signal duration, attenuation of low frequency components by
      using filtering processing and the criteria for abnormal SA-ECG. Subjects were 23
      patients with Duchenne's muscular dystrophy (DMD) and were divided into two
      groups by the presence of ventricular tachycardia (VT). Age-matched healthy
      volunteers were obtained as controls. Abnormal SA-ECG was identified from the
      data in the controls as over 97 percentile of H/L ratio. Frequency domain
      analysis from last 40 ms of QRS wave to 80 ms of ST segment was most capable to
      distinguish the DMD patients with VT from the patients without VT, compared to
      analysis from last 20 ms. Whereas, analysis from QRS onset failed to detect VT
      patients. Although filter processing reduce the power of low frequency and
      increase the H/L ratio, sensitivity for predicting VT was not enhanced
      significantly. In conclusion, the frequency-domain analysis during the terminal
      40 ms of the QRS complex and 80 ms of ST segment was most optimal condition to
      distinguish the DMD patients with VT.

PMID- 8256048
TI  - [Effective dose of flecainide for arrhythmia in children].
AB  - Nine children with arrhythmia (1 automatic atrial tachycardia, 1 premature
      ventricular construction, and 7 ventricular tachycardia) who started oral
      treatment using flecainide were studied. All but 2 cases (1 post operative
      ventricular septal defect, 1 post operative tetralogy of Fallot) had ostensibly
      normal heart on physical examination, chest X ray and echocardiogram. To raise
      serum level above 200ng/ml, flecainide dose over 80mg/m2 or 3mg/kg was needed.
      There was negative correlation between dose (y: mg/kg) and age (x: year) (y = 5.2
      0.16x, r = 0.88) in this group. No serious side effect indicating the need to
      discontinue further medication was detected. In electrocardiogram, PR, QRS and QT
      interval was not changed before or after the medication. Premature ventricular
      contraction disappeared in 2 of 8 cases (25%), decreased in number in 3 (38%),
      did not change in 1 (13%) and increased in number in 2 (25%). However ventricular
      tachycardia rate decreased or disappeared in all of the 5 cases whose ventricular
      tachycardia was detected in Holter electrocardiogram. Flecainide seems more
      effective for sustained ventricular tachycardia than for nonsustained ventricular
      tachycardia.

PMID- 8256049
TI  - [Comparison of standard-dose epinephrine and high-dose epinephrine in
      cardiopulmonary arrest outside the hospital].
AB  - We compared high-dose epinephrine (HDE) with standard-dose epinephrine (SDE) in
      improving the outcome of resuscitation after out-of-hospital cardiopulmonary
      arrest. The SDE group received epinephrine 1mg, and the HDE group received
      epinephrine 5mg respectively every 5 minutes until the return of spontaneous
      circulation. There were no significant differences between the SDE group and the
      HDE group in the rate of return of spontaneous circulation, rate of successful
      resuscitation and neurologic outcome. However, the rate of successful
      resuscitation tended to be higher in the SDE group. The ineffectiveness of HDE
      was considered to be due to the existence coronary artery diseases in the
      majority of patients, or increase in myocardial oxygen demand by the beta 1
      adrenergic effects of epinephrine.

PMID- 8256050
TI  - [Assessment of myocardial perfusion abnormalities in patients with apical
      hypertrophic cardiomyopathy using exercise 201Tl scintigraphy].
AB  - Regional myocardial perfusion abnormalities commonly occur during exercise in
      patients with hypertrophic cardiomyopathy (HCM). Exercise 201Tl myocardial
      scintigraphy has provided a noninvasive means of identifying myocardial perfusion
      abnormalities in patients with HCM. On the other hand, apical hypertrophic
      cardiomyopathy (APH) is reported as a subtype of HCM. Whether APH is essentially
      equal to HCM or not is controversial. To assess myocardial ischemia in patients
      with APH, we studied 28 patients with APH, with exercise 201Tl SPECT. Myocardial
      perfusion images were obtained immediately after submaximal exercise and again
      after a 3-hour delay. Regional perfusion defects during exercise were identified
      in 19 of the 28 patients (68%) with APH. Complete reversible defects were
      observed in 15 (79%) patients with APH. Although perfusion defects were present
      in all regions of the left ventricle in patients with HCM, they were present only
      in the apical region in patients with APH. Thus, reversible 201Tl perfusion
      abnormalities commonly occur during exercise in patients with APH as well as in
      patients with HCM.

PMID- 8256051
TI  - [Two cases of Swyer-James syndrome].
AB  - Case 1: 55-year-old male was admitted to our hospital for further examination of
      increased transparency of X-ray in the left lower lung. He had history of
      pneumonia in his childhood. Left bronchography revealed mild cylindrical bronchi
      ectasia in the proximal bronchi but poor filling by contrast in the peripheral
      bronchi. Case 2: 61-year-old male was referred to our hospital with palpitation
      and dyspnea. Chest X-ray film revealed hyperlucency of the left lower lung. The
      ventilation scan showed a marked decrease in ventilation to the left lung and air
      trapping was present in the left lung. The perfusion scan showed a matched
      decrease in blood supply to the left lung. In both cases, pulmonary arteriogram
      showed narrowed and withered-tree-like left pulmonary arteries. From these
      clinical findings, we diagnosed these two cases as Swyer-James syndrome. We are
      reporting two cases of Swyer-James syndrome and describing the clinical feature,
      differential diagnosis and etiology of the syndrome.

PMID- 8256052
TI  - [Successful documentation by coronary angiography of spontaneous simultaneous
      multivessel coronary spasm in a variant angina patient: a case report].
AB  - A 59-year old female who complained of chest discomfort was admitted to our
      hospital. Electrocardiogram (ECG) on admission and treadmill exercise test showed
      negative for ischemia. She underwent coronary arteriography. Initial angiography
      showed there was no significant coronary arterial stenosis. However, when we were
      preparing the spasm provocation test, she complained of the same kind of chest
      discomfort as she had felt before. We found that ST segment was elevated in both
      the anterior and inferior leads on the ECG. Coronary arteriography showed that
      severe spasm occurred in both the left anterior descending artery (Seg. 6) and
      the right coronary artery (Seg. 1). Heart rate decreased and electromechanical
      dissociation occurred. She temporarily lost consciousness. After cardiopulmonary
      resuscitation, she recovered and the elevation of ST segment returned on the ECG.
      This is the first case report which has documented spontaneous simultaneous
      multivessel coronary spasm by coronary arteriography.

PMID- 8256053
TI  - [Lethal arrhythmias in a patient with coarctation of the aorta and severe heart
      failure: their control by combination of low dose amiodarone with procainamide
      for 3 years].
AB  - In 1970, a 19 year-old man was diagnosed as having coarctation of the aorta
      (CoA). But the patient and his family rejected further examination for CoA and
      high blood pressure was treated after that time. When the patient was 37 years
      old, he was admitted to our hospital because of congestive heart failure. During
      the 2nd admission for determining the operability of CoA in December, 1988, non
      sustained ventricular tachycardia was detected. Immediately, intravenous
      administration of lidocaine or/and mexiletine were started. However, cardiac
      arrest occurred. After his recovery, lethal ventricular arrhythmias were still
      observed frequently despite administration of class Ia or Ib antiarrhythmic
      drugs. Oral amiodarone administration (600 mg) with procainamide (1000 mg) was
      started on 1st of May, 1989. Axillo-femoral bypass graft was performed during the
      2nd admission because curable operation was abandoned because of severely
      impaired cardiac function. Subsequently, the patient was admitted 5 times due to
      exacerbated congestive heart failure. However, lethal arrhythmias were able to be
      controlled by the combination of low dose amiodarone (100-200 mg) with
      procainamide until he died of congestive heart failure on 9th of May, 1992. We
      reported a rare adult case with CoA and severe heart failure. Lethal arrhythmias
      in this case were well controlled by the combined administration of low dose
      amiodarone with procainamide regardless of severely impaired cardiac function.

PMID- 8256054
TI  - [Adult case of aortopulmonary window with aortic regurgitation: a case report].
AB  - A 45-year-old woman was admitted to our hospital because of the evaluation of
      heart murmur. Her height was 152 cm and body weight was 46 kg. The physical
      examination showed a grade 4 continuous murmur widely audible on the anterior
      chest wall. The chest X-ray film was normal. The electrocardiogram showed
      premature ventricular contractions and left ventricular (LV) hypertrophy. The two
      dimensional echocardiogram demonstrated the presence of moderate aortic
      regurgitation (AR), however, aortopulmonary window could not be detected. The
      aortic valve showed neither atherosclerotic nor rheumatic changes. At cardiac
      catheterization, pulmonary artery (PA) pressure was 20/11 mmHg and aortic
      pressure was 133/60 mmHg, and a step-up of O2 saturation between right ventricule
      and pulmonary artery (PA) was demonstrated. The aortography revealed an
      aortopulmonary window between the proximal ascending aorta and the main PA, and
      grade 2 AR. The pulmonary to systemic flow ratio averaged 1.5:1. The coronary
      artery and the LV wall motion was normal. Aortopulmonary window is a very rare
      anomaly and often requires operation in childhood because of its large left-to
      right shunt in most cases. Neither an asymptomatic adult case with this anomaly
      nor a case with AR has not been reported so far.

PMID- 8256055
TI  - [A case of life-threatening ventricular arrhythmias probably due to psychotropic
      drugs].
AB  - We present a case provoked life-threatening ventricular arrhythmias probably due
      to psychotropic drugs. The patient was a 55-year-old man who had previously twice
      operations of aortic valve replacement (AVR). The signs of cardiac failure were
      recurrently appeared from the end of 1991, and he had received promethazine and
      sulpiride for his depressive state. From cardiac catheterization, we planned his
      third AVR. The electrocardiographic (ECG) QTc interval was prolonged to 0.48
      seconds on this admission. In March 1992 syncopal attack appeared suddenly, and
      his monitor ECG revealed frequent polymorphous ventricular tachycardia (VT) and
      Torsade de Pointes (Tdp). These arrhythmias stopped by emergent cardiac pacing.
      After discontinuing these psychotropic drugs, no ventricular arrhythmias
      appeared. Since the patient complained severe insomnia one month before
      operation, the diminished dose of psychotropic drugs (promethazine and
      levomepromazine) was readministered. Ten days after the operation, syncopal
      attack reappeared and his ECG recorded frequent VT and Tdp. During both syncopal
      attacks his serum potassium and magnesium were within normal limits. Two days
      later, he died from multi-organ failure. We concluded that life-threatening
      arrhythmias such as VT and Tdp might develop under the administration of mild
      psychotropic drugs (promethazine or levomepromazine), therefore, must better take
      a care of ECG changes in cases of using any psychotropic drugs.

PMID- 8256056
TI  - [Physical examination in the monitoring of normal pregnancy].

PMID- 8256057
TI  - [Ultrasonography in normal pregnancy].

PMID- 8256058
TI  - [Hematological problems in pregnancy].

PMID- 8256059
TI  - [Infectious diseases and pregnancy].

PMID- 8256060
TI  - [Pregnancy and sports].

PMID- 8256061
TI  - [Pregnancy and travel].

PMID- 8256062
TI  - [Pregnancy and sex].

PMID- 8256063
TI  - [Psychiatry and health policy. Introduction].

PMID- 8256064
TI  - [Psychiatry and civil servant].

PMID- 8256065
TI  - [Cost and benefits in social psychiatry: should one economize or develop?].

PMID- 8256066
TI  - [Psychiatry in Valais: perspectives and developments].

PMID- 8256067
TI  - [The physician facing deviant behavior and prison system: elaboration of a
      specific health policy].

PMID- 8256068
TI  - [Procedures in economics: from an authoritarian method to a participative
      method].

PMID- 8256069
TI  - [Ambulatory charges in psychiatry: description and comments].

PMID- 8256070
TI  - [Psychogeriatrics in the medical-social network].

PMID- 8256071
TI  - [Alcoholism: a paradigm for a new health policy].

PMID- 8256072
TI  - [The Clinic of Vallon: from concept to practice].

PMID- 8256073
TI  - [The place of psychiatry in the management network of drug addicts: apropos of
      public psychiatry in Lausanne].

PMID- 8256074
TI  - [Psychiatry and drug addiction in Geneva].

PMID- 8256075
TI  - [Psychiatry in the management network of drug addicts].

PMID- 8256076
TI  - The effect of ostial opening on experimental maxillary sinusitis in rabbits.
AB  - Obstruction of the natural ostium is known to be one of the major factors in the
      pathogenesis of maxillary sinusitis. To explore the therapeutic effect of ostial
      patency, sinusitis was induced in 32 rabbits by obstruction of the natural ostium
      and inocculation of Streptococcus pneumoniae. They were divided into two groups:
      the first ("open") group included 16 rabbits with experimentally induced
      sinusitis, from which bone chips for obstruction of the natural ostium were
      removed after a period of 5 days, and the second ("closed") group included 16
      rabbits with continuous obstruction of the natural ostium. The induction of
      sinusitis was found to be successful in all cases, when examined after five days.
      The amount of nasal and sinus secretion as well as histopathological findings of
      the sinus mucosa were investigated with light microscopy, scanning and
      transmission electron microscopy, two and four weeks after induction of
      sinusitis. The findings were significantly improved in the "open" group.

PMID- 8256077
TI  - Effect of S-carboxymethylcysteine on ciliary activity in chronic sinusitis.
AB  - This study was designed to investigate the possible pharmacological effect of S
      carboxy-methylcysteine (S-CMC) on the ciliary activity, using an in vitro
      experimental system after removing mucus. Ciliary activity from healthy rabbit
      maxillary sinus and from healthy human nasal mucosa demonstrated no significant
      change in RPMI 1640 containing S-CMC. On the other hand, the effect of S-CMC on
      the reduced ciliary activity from patients with chronic sinusitis was quite
      varied among the cases examined. S-CMC demonstrated no stimulatory effect on the
      beating activity of cilia that have a baseline activity of less than 400
      beats/min. However, S-CMC was able to enhance the beating activity of cilia that
      demonstrated a baseline activity of more than 400 beats/min. S-CMC at 0.5%
      induced a larger ciliostimulatory effect than 0.05% S-CMC. In conclusion, our
      study has clearly demonstrated that S-CMC could directly enhance ciliary activity
      of chronic sinusitis in the absence of significant organic change of ciliated
      cells.

PMID- 8256078
TI  - External rhinoplasty. Comparison of two approaches.
AB  - This paper compares two different techniques of external rhinoplasty, in which
      the lower lateral cartilages are either elevated with the columellar skin (i.e.,
      Gillies-Meyer approach) or left attached to the main body of the nose (i.e.,
      Rethi-Sercer approach). Both techniques give good access and exposure, but we
      found the Gillies-Meyer approach somewhat easier to perform. It can also be used
      to provide extended access if difficulty is experienced during a closed
      rhinoplasty operation.

PMID- 8256079
TI  - Endonasal endoscopy and posterior epistaxis.
AB  - The availability of a comprehensive range of endonasal telescopes facilitates
      systematic examination of the nasal cavity. Epistaxis is normally divided into
      anterior and posterior. Posterior epistaxis is diagnosed when anterior rhinoscopy
      fails to visualize anterior-located bleeding points. With the aid of endonasal
      endoscopy the exact location of bleeding points can be identified and diathermy
      applied under direct vision. Twenty-seven cases of the so-called posterior
      epistaxis were treated successfully by endonasal endoscopy. The technique is
      particularly useful during acute nose bleeds, it shortens hospital stay, and
      reduces the discomfort inflicted by the presence of nasal packing. The need for
      blood transfusion is reduced by using endonasal endoscopy in the acute stage of
      epistaxis.

PMID- 8256080
TI  - The influence of beta-adrenoceptors on nasal mucosal function.
AB  - The aim of the study was to elucidate the role of beta-adrenoceptors in normal
      human nasal mucosa. In two studies, beta-receptor function was tested by the
      application of agonists and antagonists. Measurements of nasal secretion and
      nasal peak expiratory flow were performed at 4-min intervals, during 12 min of
      rest, pre- and post-treatment, 12 min of exercise and 20 min of recovery. In
      Study 1, placebo was compared with 100 micrograms salbutamol and 2 mg
      propranolol. Neither placebo nor 100 mg salbutamol affected nasal secretion
      production at rest, but propranolol caused a transient significant increase (p <
      0.05). Exercise significantly increased secretion production in all three
      treatment groups (p < 0.05). Nasal peak expiratory flow was not altered at rest,
      but increased significantly (p < 0.05) during exercise in the three treatment
      groups. In Study 2 placebo was compared with 200 mg salbutamol, 80 micrograms
      isoprenaline and 2 mg atenolol. Secretion production was not altered at rest by
      any treatment and increased during exercise in all four (p < 0.05). There was no
      significant difference between weights of secretions produced between any of the
      treatment groups during exercise. Salbutamol significantly decreased nasal peak
      expiratory flow at rest compared with placebo (p < 0.05). During exercise nasal
      peak flow increased in all groups, but peak exercise values were significantly
      reduced by both salbutamol and isoprenaline (p < 0.05). Atenolol appeared to have
      no effect on nasal peak expiratory flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256081
TI  - Immunocompetent cells in human nasal polyps and normal mucosa.
AB  - The distribution of T- and B-lymphocytes, HLA-DR-expressing cells, and
      macrophages was determined using monoclonal antibodies in frozen biopsy sections
      of nasal polyps from 12 patients, and of nasal mucosa from five disease-free
      controls. The relative proportion and spatial distribution of different lymphoid
      cells was similar with regards to both nasal polyps and normal mucosa. Numerous
      scattered T lymphocytes (Leu4-positive) and HLA-DR-expressing
      macrophage/dendritic-like cells were shown and tended to accumulate in the
      subepithelial areas. Aggregates of T lymphocytes and HLA-DR-positive cells were
      also found close to deeper glands. In the submucosal clusters, the Leu3a-positive
      ("helper/inducer") cells were more common than the Leu2a-positive
      ("suppressor/cytotoxic") cells. Furthermore, a number of epithelial, non-lymphoid
      cells were found to express the HLA-DR antigen, which suggests an active role for
      the epithelium in the immunological response of the normal mucosa as well as that
      of the nasal polyp.

PMID- 8256082
TI  - A randomized double-blind trial of glypressin in the management of acute
      epistaxis.
AB  - This is the first randomised double-blind trial of glypressin in the treatment of
      acute epistaxis, where no localized bleeding point was found and where the
      patient would normally be treated with a form of nasal packing. It shows a
      statistically significant benefit with the intravenous drug compared to placebo.
      In addition, the dose of glypressin used to achieve control appears to be free of
      major side effects. Acute epistaxis is a common problem, nasal packing is
      unpleasant and not without side effects, and therefore an alternative form of
      treatment would have clear advantages. The mechanism of action of glypressin is
      discussed along with the implications of the results for the future role of
      glypressin in the treatment of acute epistaxis.

PMID- 8256083
TI  - An unusual case of sphenoid sinus mucocele with severe intracranial extension.
AB  - We present an unusual case of sphenoid sinus mucocele with severe intracranial
      extension, which was diagnosed and treated at the AHEPA General Hospital,
      University of Thessaloniki, Greece. The patient was a 54-year-old female who
      presented with endocrine, nasal and ophthalmological symptoms, and headache. She
      was successfully treated by surgery using an intranasal approach. While
      presenting this case, we briefly review the literature on the subject of sphenoid
      sinus mucoceles.

PMID- 8256084
TI  - Cholesterol granuloma of the frontal sinus. A case report.
AB  - A rare case of cholesterol granuloma of the frontal sinus is reported. The
      pathogenetical mechanisms and the tumour's behaviour are discussed on the basis
      of the patient's, the radiologic examination and the pathologist's finding's. A
      follow-up of three years is given.

PMID- 8256085
TI  - Demonstration of bilateral cholinergic secretory response after unilateral nasal
      cold, dry air challenge.
AB  - Cold, dry air (CDA) causes rhinorrhoea and nasal congestion in some individuals.
      This response can be mimicked in the laboratory by exposing susceptible
      individuals to cold, dry air nasal breathing. One of the characteristics of this
      response is that nasal secretions are produced by both nostrils after a
      unilateral challenge. This study evaluated the role of cholinergic innervation on
      the ipsi- and contralateral responses to unilateral CDA challenge. Twelve
      individuals participated in a randomized, double-blind, placebo-controlled, 3-way
      crossover study where local atropine and placebo were alternated ipsilateral and
      the contralateral to the CDA challenge. The reproducibility of the model,
      assessed by the response after pre-treating with placebo, was excellent; after
      placebo, the ipsilateral response was double the size of the contralateral.
      Regardless of the site of application, atropine significantly reduced the
      secretory response to CDA by 60-70%. However, significant secretions were still
      induced by CDA, even after atropine treatment. We conclude that cholinergically
      mediated neuronal pathways play a major role in the nasal secretory response to
      CDA. Additional neuronal pathways may, however, be involved. This method is a
      tool to understand the different components of the mucosal response to a cold and
      dry environment.

PMID- 8256086
TI  - Identification of a zinc finger encoding gene in Onchocerca volvulus.
AB  - Eukaryotic transcription factors can be identified and classified according to
      conserved DNA-binding motifs and conserved regulatory domains. The functional and
      structural analysis, and the conservation of these genes among metazoans
      emphasizes the importance of these DNA-binding proteins in development and
      differentiation. In order to identify genes with common DNA-binding motifs in the
      genome of Onchocerca volvulus we have cloned a zinc finger encoding gene of the
      structure C2-H2. Using the Caenorhabditis elegans sex determining tra-1 gene as a
      probe we have identified two tra-1 related genes in the genome of O. volvulus.
      The zinc finger region of one of these genes (OvZf1) was subcloned and sequenced.
      The predicted protein has at least eight consecutive zinc fingers and each finger
      possesses the characteristic paired cysteine- and histidine residues and the
      proper spacing of the amino acids between the conserved residues.

PMID- 8256087
TI  - Antibody responses to Onchocerca volvulus in Ecuadorian Indians and blacks.
AB  - In Ecuador, previous epidemiological studies of onchocerciasis affecting a
      population consisting of Blacks of African origin and Amerindians of the Chachi
      tribe, have demonstrated different frequencies of clinical disease manifestations
      in each racial group. To explore the possibility of differential antibody
      responses to O. volvulus antigens in this population, a subset of sera from these
      two groups of Ecuadorians with onchocerciasis was analyzed for antibody to O.
      volvulus antigens using ELISA and Western blot techniques. Significantly higher
      levels of immunoglobulin against O. volvulus were demonstrated in Chachi Indians
      compared to native Blacks of African origin: total Ig (p = 0.049), IgG (P =
      0.002) IgG4 (p = 0.019) and IgA (p = 0.035). Western blot analysis of sera from
      41 persons demonstrated more intense and more frequent recognition of low
      molecular weight parasite antigens in the Chachi compared to a similar group of
      male and female Ecuadorian Blacks. These data suggest that the intensity of
      antibody responses to O. volvulus antigens may reflect the influence of racial
      factors in the pathogenesis of onchocerciasis in Ecuador.

PMID- 8256088
TI  - Absence of sperm from the seminal receptacle of female Onchocerca volvulus
      following multiple doses of ivermectin.
AB  - It is already known that multiple doses of ivermectin have a profound effect on
      embryonic development in Onchocerca volvulus and that this appears to operate
      mainly at the single cell stage. To investigate this further, we examined adult
      female O. volvulus originating from patients treated either with placebo or one,
      four or five doses of ivermectin. The reproductive organs were dissected out of
      the worm and examined for evidence of oogenesis and for the quantity of sperm and
      oocytes in the seminal receptacles. A single dose of ivermectin had no measurable
      effect on oogenesis or on the amount of sperm and oocytes compared to placebo.
      However after multiple doses of ivermectin a significantly lower proportion of
      seminal receptacles contained sperm and there was a significantly higher
      proportion of ovaries with impaired oogenesis compared to placebo. It is
      concluded that the reduction in the number of multicellular embryonic stages from
      worms exposed to multiple doses of ivermectin is due, at least in part, to a
      major reduction in the effective insemination of female worms and to a minor
      impairment of oogenesis.

PMID- 8256089
TI  - Distribution of onchocerciasis in selected river basins of four west African
      countries.
AB  - Detailed epidemiological mapping of eight river basins was conducted in four West
      African countries as part of an effort to identify the communities at risk of
      onchocercal blindness to guide a programme of large scale ivermectin
      distribution, attempting control of eye disease. The results show a surprising
      variability of pattern in the geographical distribution of intensity of
      onchocerciasis infections in the communities of the river basins investigated.
      These patterns were at time very different from what was expected on the basis of
      the available entomological and demographic information. The technique of
      detailed mapping proved very useful in achieving an excellent coverage of the
      communities at risk of onchocercal blindness where, so far, satisfactory
      treatment coverage has been attained for four consecutive yearly treatments.

PMID- 8256090
TI  - Chromosomal diagnostic criteria for some members of Simulium damnosum complex in
      east Africa.
AB  - Identification of Simulium damnosum s.l. vectors of onchocerciasis demands
      adequate knowledge of the chromosomal features that distinguish human-biting
      members from nonanthropophilic forms. In this study, 955 S. damnosum larvae
      collected from various geographical locations in Tanzania were chromosomally
      analyzed. 358 larvae from small mountain streams in the northeast and central
      regions of Tanzania, were identified as mainly Nyamagasani and Sanje forms, with
      only one Kiwira form. 378 larvae from plain and lowland rivers, also in the
      northeast and central regions, were identified as Nkusi, Kisiwani and Kibwezi
      forms. Chromosomal examination of 219 larvae from the southern highlands zone
      revealed the presence of Kiwira and Nyamagasani forms. A further 27 larvae of S.
      damnosum complex collected from 5 rivers in Uganda were identified as Sebwe and
      Nkusi forms. Chromosomal photomicrographs on which the distinguishing characters
      were based are provided. These observations are discussed in the light of
      previous studies carried out on the S. damnosum cytological forms in Eastern
      Africa.

PMID- 8256091
TI  - Anti-Dirofilaria immitis IgE: seroepidemiology and seasonal variation in an
      exposed human population.
AB  - The seroprevalence of seasonal variation of human anti-Dirofilaria immitis IgE
      levels were studied in an area where specific IgM and IgG had been previously
      investigated. An antibody capture ELISA assay was used to detect specific IgE.
      The IgE seroprevalence observed in the whole population was 12.6%. No specific
      IgE was detected in atopic individuals or in sera from people suffering other
      helminthiases. The distribution of the IgE anti-D. immitis seroprevalence by age
      groups did not show differences. Females had significantly higher levels than
      males. This isotype of immunoglobulin peaks in July, decreasing sharply in
      October, and persisting at a level similar to that of a non exposed population
      during the rest of the year. No specific IgE were detected in subjects with
      pulmonary alterations related to the parasite, suggesting a possible relationship
      between the clinico-radiological status and the type of immunoglobulin
      synthesized in subjects infected by D. immitis.

PMID- 8256092
TI  - Schistosomiasis and intestinal parasites in rural villages in southwest Nigeria:
      an indication for expanded programme on drug distribution and integrated control
      programme in Nigeria.
AB  - A cross sectional survey of schistosomiasis, intestinal parasite infections and
      pattern of schistosomiasis transmission was undertaken in four rural villages
      around the Erinle dam, Nigeria. The prevalence of Schistosoma haematobium ranged
      from 10% to 60%. 30% of infected school children excreted over 50 eggs/10 ml
      urine and high rates of haematuria, proteinuria, leucocyturia and nitrites in
      urine were observed in infected children and the villagers. Prevalence of
      infection with S. mansoni ranged from 11.4% to 36.8%. Intensity of infection
      based on geometric mean eggs/gram of faeces ranged between 100 and 545.7 eggs/g.
      Malacological surveys showed that Biomphalaria pfeifferi was the predominant
      potential snail hosts recovered at all the contact sites. Higher infections with
      schistosome parasites were also recorded for B. pfeifferi than Bulinus globosus.
      The pattern of transmission of schistosomiasis by the snails is consistent and
      makes incorporation of community-based focal application of a molluscicide such
      as Tetrapleura tetraptera in integrated control of schistosomiasis feasible in
      the area. Prevalence and intensity with Ascaris lumbricoides was high. The
      highest prevalence was 68.9% while the highest intensity of infection was 2,440.9
      eggs/gram of faeces. Multiple infections occured with various combinations of
      Ascaris lumbricoides, hookworm, S. haematobium, Fasciola gigantica, S. mansoni,
      and Entamoeba histolytica (as double, triple or quadruple infections). The
      results suggest an integrated approach to the control of schistosomiasis and
      intestinal parasites in this part of the country.

PMID- 8256093
TI  - An epidemiological assessment of Ambrosia maritima on the transmission of
      schistosomiasis in the Egyptian Nile Delta.
AB  - Ambrosia maritima (Damsissa), a proven molluscicide, was investigated in a seven
      year epidemiological trial in four villages in the northern Egyptian Nile Delta.
      Schistosoma mansoni prevalence and other measures of infection were initially
      high in the four villages before the trial began. Two villages were used to test
      the impact of A. maritima application both on snail populations and on infection
      in the village population. Two villages were held as controls and not treated
      with A. maritima. The entire population of all four villages was included in the
      study. Prevalence and other measures of infection fell dramatically following
      treatment with praziquantel 40 mg kg-1 body weight. On annual follow ups, the
      prevalence of infection and geometric mean egg counts began to increase back to
      original levels in both test and control villages; age adjusted incidence rates
      were lower in one test village, but higher in the other when compared to the
      control villages. Snail populations were destroyed in the treated canals and
      drains located near the test villages. The lack of a clear epidemiologic impact
      is discussed.

PMID- 8256095
TI  - Combination of praziquantel and albendazole in the treatment of hydatid disease.
AB  - This is a preliminary report on the first four patients with pelvic, abdominal
      and thoracic hydatid disease, who are receiving combined medical treatment
      (albendazole 400 mg bd on monthly courses plus praziquantel 50 mg/kg in different
      regimens). Response to treatment was monitored clinically, biochemically and
      radiologically by means of computed tomography (CT) and abdominal sonography
      (US). No side effects were observed in the course of this treatment. After 3
      months of using the combined treatment, cysts disappeared completely in three
      patients and in the fourth patient, a reduction in cysts size by more than 75%
      after two months combination treatment was observed. This combination therapy as
      a human trial has not been reported previously. This preliminary report shows
      that the response to combined treatment is better and much quicker compared to
      albendazole alone.

PMID- 8256094
TI  - Use of human infection and vaccine-protected baboon sera for the characterisation
      of cloned Schistosoma haematobium antigen genes.
AB  - A Schistosoma haematobium adult worm cDNA library was screened with sera from
      demonstrably immune baboons (mean worm reduction 94%) vaccinated with highly
      irradiated cercariae (VBabS) and also with sera from adult S. haematobium
      infected humans (HIS Sh). As species-specificity is a characteristic feature of
      the immunity induced by irradiated cercariae, S. haematobium species-specific
      clones were identified by rescreening positives with sera from S. mansoni
      vaccinated animals or infected humans. Six species-specific clones, 3 initially
      detected with vaccinated baboon sera (D11, D14 and D26) and 3 with human
      infection sera (E1, E2 and E16) were further characterized by Western blotting.
      The three HIS-selected clones did not react significantly with VBabS or acutely
      infected baboon sera (ABabS) while D11, D14 and D26 showed increasing reactivity
      with successive vaccinations. In addition D11 and D14 but not D26 responded to
      ABabS. When tested against HIS Sh from 24 patients of varying ages, D11 and D26
      reacted most frequently with sera from individuals in the older age groups (> 17
      yrs). A species cross reactive clone, D12, which was used as a positive control
      throughout, was found to react with all schistosome specific sera tested.

PMID- 8256096
TI  - Superoxide dismutase of Trichinella spiralis and Trichinella pseudospiralis
      larvae.
AB  - The aim of this study was to compare the in vitro and in vivo activities of
      superoxide dismutase, an enzyme acting against free-radicals, in Trichinella
      spiralis and T. pseudospiralis isolates. In vitro, the activity of the superoxide
      dismutase in T. pseudospiralis was determined to be about two times higher than
      in T. spiralis. Only one band representing superoxide dismutase was found by
      electrophoretic analysis. In vivo, in muscles infected with T. spiralis, a strong
      histochemical reaction in the capsule and the layer directly adhering to it was
      found. In muscles infected with T. pseudospiralis, the activity was most marked
      in the vicinity of the larva and becomes less marked with the distance. The
      character of the reaction indicated that the enzyme is excreted by the larvae.

PMID- 8256097
TI  - Proteolytic enzymes of pathogenic and non-pathogenic strains of Acanthamoeba spp.
AB  - The aim of this work was biochemical characterization and classification of
      proteinases in pathogenic and non-pathogenic strains of Acanthamoeba spp. The
      authors showed two proteinase (acid 35 kDa and alkaline 65 kDa) which could be
      separated electrophoretically. Acid proteinase was inhibited by serine proteinase
      inhibitors such as DIFP. The second enzyme which was active at alkaline pH, was
      enhanced by EDTA and inhibited by iodoacetate (IAA) and (p-CMB) p
      chloromercuribenzoate. These substances are known to inhibit cysteine type
      proteinases. The alkaline proteinase was more distinctively active in pathogenic
      strains and belongs to cysteine class (EC 3.4.22), whereas the acid proteinase
      was similar active in pathogenic and non-pathogenic strains and belong to serine
      class (EC 3.4.21).

PMID- 8256098
TI  - A comparative study of diagnosis by the polymerase chain reaction and by current
      clinical methods using biopsies from Colombian patients with suspected
      leishmaniasis.
AB  - The results of a preliminary trial are reported in which the diagnostic value of
      a Polymerase Chain Reaction (PCR) specific for Leishmania of the subgenus Viannia
      was compared with that of currently recommended methods. These methods were
      microscopic examination of dermal scrapings, in vitro culture of both patient
      biopsies and aspirates, an in vitro culture of hamster aspirates following
      inoculation with patient biopsies. The tests were performed on biopsies of
      Colombian patients with leishmaniasis or with nonleishmanial ethiologies. The
      outcome of this trial was that PCR was consistently more sensitive than any of
      the four currently recommended methods of diagnosis, an gave results much faster
      than the three culture-based methods. Clinical specificity did not match the
      absolute specificity obtained in the laboratory when tested against purified
      kDNAs from various Leishmania species. This is thought to be due to the small
      sample size and to possible subclinical presence of the parasite in the
      population. The results nevertheless show that, given a more extensive trial
      directed at clinical validation, PCR can provide the means for early and rapid
      diagnosis of leishmaniasis. This should reduce morbidity and treatment costs.
      Further improvements to the method, its introduction in endemic settings and its
      possible further clinical uses are also discussed.

PMID- 8256099
TI  - A comparison of in vitro assay systems for the measurement of drug sensitivity of
      Trypanosoma evansi.
AB  - Two in vitro assay systems were investigated for their effectiveness in detecting
      the sensitivity of Trypanosoma evansi stocks to the trypanocide suramin. These
      assay systems measured 1) incorporation of radiolabelled nucleic acid precursor,
      hypoxanthine; and 2) pyruvate production. They were compared with the direct
      counting method in which numbers of motile trypanosomes were estimated using a
      Neubauer haemocytometer chamber. Three stocks of T. evansi were tested-2 suramin
      sensitive stocks from Indonesia, TREU 1840 and TREU 1981, and a suramin resistant
      stock from the Sudan, TREU 2136. Each assay system distinguished between the
      suramin sensitive and resistant stocks. However, inhibition compared to untreated
      control cultures was less when assessed from pyruvate concentration in culture
      supernatants than by direct counting. The length of incubation with drug before
      addition of radio-label was the most important variable in the hypoxanthine
      incorporation assay. A pre-incubation time of 16 hours with the drug before
      adding the label for the further 8 hours of the assay was found to be the most
      sensitive. Under these conditions, the IC50 values (drug concentrations causing
      50% inhibition) were similar to those obtained from direct counts. Pre-incubation
      of parasites with drug before adding the label resulted in a decrease of the
      IC50. These results suggest that the discrepancy between the levels of pyruvate
      production and relative growth at inhibitory concentrations of the drug are due
      to metabolism by the parasites during the initial stages of the assay, before the
      drug has began to inhibit cell growth.

PMID- 8256100
TI  - Man-fly contact in the Gambian trypanosomiasis focus of Nola-Bilolo (Central
      African Republic).
AB  - A study using bipyramid tetse fly traps in the Nola-Bilolo sleeping sickness
      focus (Central African Republic) reveals ecological and behavioural differences
      between two vectors, Glossina palpalis palpalis and G. fuscipes fuscipes. The
      latter species inhabits mainly open water sites and surrounding forest, whereas
      G. p. palpalis occurs mainly in coffe plantations near villages. Consequently,
      the man-fly contact differs considerably according to the species. The intensity
      of trypanosomiasis transmission, estimated by the probable distribution of cases,
      showed significant positive correlation with the density of the flies. Analysis
      of the fly blood meals in two villages show that, unlike G. g. palpalis, G. f.
      fuscipes feeds on men more than on pigs. Trypanosoma vivax infection was observed
      only in G. fuscipes fuscipes. The differences in occupation of the environment
      between the two vectors must be taken in account in trapping programmes which may
      modify this distribution.

PMID- 8256101
TI  - An outbreak of vampire bat bite in a Brazilian village.
AB  - An outbreak of 26 cases of vampire bat bite in one month in the rural area of
      Honoropolis, a Brazilian village, is reported. All patients were bitten during
      the night, when they were asleep, and most bites were on their toes. No
      complication attributed to the bite was reported. The patients were given
      prophylactic antirabies serum and rabies vaccine. Control of the outbreak was
      achieved by visiting bat roosting sites, smearing captured vampire bats (Desmodus
      rotundus) with a paste of 2% warfarin in vaseline, and releasing them. No case of
      human or animal rabies was diagnosed in a 5-month follow-up. A possible
      explanation for the outbreak of bat bite is that, because of man-induced
      environmental modifications in their habitats, vampire bats in Honoropolis now
      live in the peridomiciliar area, where people are more exposed to their bites. An
      alternative explanation is related to the use in cattle of a pyrethroid
      insecticide to control the horn fly, Haematobia irritans, as both events were
      temporally related. The insecticide could have had a repellent effect on bats,
      that then started to seek alternative food sources.

PMID- 8256102
TI  - Further data on the compatibility between Schistosoma intercalatum (lower Guinea
      strain) and Bulinus forskalii: epidemiological consequences.
AB  - A study of the compatibility between Schistosoma intercalatum from Cameroon and
      its potential vectors Bulinus forskalii from Cameroon, Equatorial Guinea, Ivory
      Coast and Niger has been carried out. As compatibility test, the snail infection
      test, completed by an histological study, was used. Snail infection experiments
      showed that all the populations of B. forskalii we tested are very good potential
      vectors, with infection rates ranging between 76.5 and 93%. The histological
      study revealed no defense reaction in the snails, which confirms the perfect
      compatibility of the B. forskalii populations we studied. In an epidemiological
      perspective, this study confirms the ever present risk of extension of S.
      intercalatum parasitosis in Africa.

PMID- 8256103
TI  - A pictorial guide to the chromosomal identification of members of the Simulium
      damnosum Theobald complex in west Africa with particular reference to the
      Onchocerciasis Control Programme Area.
AB  - Simulium damnosum Theobald is made up of a complex of sibling species. Nine
      species are described in the area covered by the World Health Organisation's
      Onchocerciasis Control Programme in West Africa (OCP). These are, S. squamosum,
      S. yahense, S. canctipauli, S. soubrense, S. leonense, S. konkourense, S.
      damnosum s.s., S. sirbanum and S. dieguerense. All of them are vectors of human
      onchocerciasis, albeit to different capacities. Reliable species determination
      presently depends on larval cytotaxonomic criteria. The diagnostic chromosomal
      inversions and other micromorphological characters used in the identification of
      the species found in the OCP area are presented with figures for their
      recognition, some distributional information is also given.

PMID- 8256104
TI  - Malaria and travelers--practical aspects.
AB  - As international air travel becomes more and more common, we are witnessing an
      increase in the incidence of imported malaria caused by Plasmodium falciparum, a
      fatal variety resistant to antimalarial drugs. With the development of drug
      resistance, travelers can no longer rely on chemoprophylaxis alone for absolute
      protection against malaria; they need to take a number of complementary measures.
      The most important among these are steps to prevent mosquito bites (mosquito
      screens and nets impregnated with insecticide, insecticides and repellents in
      various formulations; nocturnal air-conditioning) which can be instituted
      anywhere. Chemoprophylaxis must be adapted in each case with regard to individual
      characteristics (laboratory and medical status), the drug used
      (contraindications, side effects) and the travel itinerary (departure date,
      places to be visited, duration of journey). The back-up treatment prescribed for
      a traveler before his departure is intended as cover in the event that the
      chemoprophylaxis used should prove to be ineffective. If people planning trips to
      malarious regions are to apply preventive measures, they have to be informed,
      aware and motivated. Information is an integral part of prevention. Objective,
      scientifically accurate information is provided by specialized centres and
      official bodies in the form of recommendations subject to regular updating. A
      recommendation of a nonmedical nature must be given by travel agents and tour
      operators, by airlines and shipping companies, embassies and consulates, and also
      by the media at peak periods of travel to the tropics. Information disseminated
      on this scale will produce the required degree of awareness, and the travelers
      targeted will then probably consult a doctor for the chemoprophylaxis they need.

PMID- 8256105
TI  - Commitment of Roche in malaria and other tropical diseases.
AB  - In the absence of a suitable malaria case definition, reliable surveillance data
      on the impact of malaria are not available. Determinants of case loads, including
      population movements, environmental changes, lack of political commitment and
      resources, and resistance to antimalarials and residual insecticides, work
      towards global deterioration. Some 90% of the Plasmodium falciparum burden is
      carried by Africa south of the Sahara. There, in 1992, the number of children
      under five years of age and exposed to high risk was about 106 million. Assuming
      a malaria attack rate of 0.5-1.5 per child per year, and a case fatality rate of
      2%, annual clinical cases and malaria deaths in this population alone come to 53
      160 million and 1-3 million, respectively. Roche, a pharmaceutical company with
      major research efforts in tropical medicine, in collaboration with research
      centers and international institutions, has recently set up a tropical medicine
      unit that coordinates and concentrates corporate efforts in this field. The unit
      aims to make affordable and innovative products available which are effective
      against major tropical diseases. A commercial product of the unit is Lariam, a
      major antimalarial used alone or in simultaneous or sequential combinations. The
      single dose combination of Lariam plus Fansidar (Fansimef) is particularly useful
      for stand-by or emergency oral therapy. Artemisinine, or its derivatives,
      followed by one to two doses of Lariam are effective against severe and
      multiresistant P. falciparum malaria. A new Roche peroxide antimalarial is
      currently in phase II clinical trials. The unit is also involved in research and
      development of malaria sporozoite and asexual blood stage vaccine candidates.

PMID- 8256106
TI  - Comparative tolerability and kinetics during long-term intake of Lariam and
      Fansidar for malaria prophylaxis in nonimmune volunteers.
AB  - One hundred and five healthy nonimmunes in Colombia took part in a randomize,
      double-blind comparison of 250 mg of Lariam (L) (active ingredient: mefloquine)
      on alternate weeks or one tablet of Fansidar (F) (active ingredients: sulfadoxine
      and pyrimethamine) weekly for malaria prophylaxis during at least six months.
      Volunteers also gave blood for determination of drug concentrations after six
      months and/or 24-27 months of prophylaxis. Twenty-five volunteers withdrew
      involuntarily when they lost their jobs in the company. Two who took L withdrew
      due to moderate diarrhea and mild nausea or headache, weakness, drowsiness and
      anxiety. One volunteer stopped taking F due to severe unilateral hypostatic
      eczema and slight S-T depressions on the ECG. The rest completed at least six
      (range 6-36) months of prophylaxis. The mean half-life for L was 26 days. The
      AUCs in the time interval 0-14 days for L varied between 19.3-31.5 mumol x
      days/l. For the main metabolite, the corresponding range was 28.8-81.3 mumol x
      days/l. The range of trough concentrations at day 0 and 14 were 0.95-2.01 mumol/l
      for L and 1.69-5.62 mumol/l for the metabolite. No differences in tolerability
      and efficacy were noted between L and F. Our kinetic results do not indicate that
      enzymatic induction or inhibition would be important during long-term prophylaxis
      with mefloquine. This favors a continued use of the drug for very long periods of
      time (= years).

PMID- 8256107
TI  - Tolerability of prophylactic Lariam regimens.
AB  - Three hundred and fifty-nine US Marines participated in a randomized double-blind
      clinical trial to assess tolerance of two prophylactic mefloquine regimens [250
      mg salt weekly (n = 157) or 250 mg daily for 3 days followed by 250 mg weekly (n
      = 46)] compared with 300 mg weekly chloroquine (n = 156) over a 12-week period.
      The study participants were seen daily for four days, then weekly for 11 weeks.
      On each visit, the subject answered two computerized questionnaires (a review of
      body systems and an evaluation of mood states), participated in a physician
      interview, and was administered medications under supervision. A random sample of
      each group was assigned to either pharmacokinetic sampling or two wear a wrist
      watch size computerized sleep monitor (actigraph). The frequencies of
      intercurrent illness and other concomitant medications were tabulated. End study
      mefloquine plasma levels were obtained on all study participants. The results
      obtained showed no compromise in function due to dizziness or incoordination in
      the mefloquine groups. Overall, both weekly mefloquine and loading dose
      mefloquine were well tolerated. Sleep disturbance and increased dream activity
      were detected in the mefloquine groups. Depressive feelings were noted in two to
      three times more individuals in the mefloquine groups than in the chloroquine
      group early in the course of the study, and resolved in the majority of subjects
      as tolerance developed. Steady state mefloquine plasma levels were attained
      rapidly with the loading dose regimen in four days versus seven weeks with weekly
      mefloquine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256108
TI  - Nairobi Hospital, Kenya: the management of nonimmune P. falciparum malaria
      abroad.
AB  - A retrospective analysis of all malaria cases admitted to the Nairobi Hospital
      was performed by reviewing patient records. Six hundred and three cases were
      recorded between the period of January 1987 and July 1990 (43 months). The mean
      age of the patients was 32.5 years and 57.5% were male. Although 81.4% were
      permanent residents of Kenya, only 18.2% could be said to have lived in a
      malarial zone. One-quarter of the patients (25.6%) admitted having had a previous
      episode of malaria, and 57.7% were taking regular chemoprophylaxis. The most
      common presenting symptoms were fever, headache, vomiting and myarthralgia; the
      most commonly recorded accompanying signs were jaundice and splenomegaly. Sixty
      patients met the criteria for severe malaria. During their hospital stay, six
      patients (1%) died; five of whom were severely ill from the time of for the USA
      and UK, especially as it represents a selected population of the more serious
      malarial cases admitted to the hospital. Therefore, it may indeed represent clear
      evidence to support the hypothesis that a high index of suspicion combined with
      early diagnosis and treatment will result in improved outcome. Comparative
      features illustrating these points are presented. As the malaria parasite, P.
      falciparum, has dynamic antimalarial sensitivity and as more travelers are under
      threat from this disease, it is vital that ignorance of this danger should not be
      allowed to put individuals at risk for death. Continuing education of both the
      traveling public and the medical profession is the only way that both parties
      will shoulder their respective responsibilities.

PMID- 8256109
TI  - Phenotypic characterization of splenic T cells from mice infected with Plasmodium
      chabaudi chabaudi.
AB  - T cells from spleens of mice infected with the erythrocytic stages of Plasmodium
      chabaudi chabaudi have been analysed with respect to their expression of surface
      molecules CD3, CD4 and CD8 and T-cell receptor (TCR) alpha beta and gamma delta.
      The majority of T cells from infected mice were alpha beta TCR+. However, there
      was an increase of approximately 8-10-fold in the proportion and total number of
      gamma delta T cells. Immunocytochemical analysis of sections of spleens taken
      from infected C57BL/6 mice during a primary infection showed that this increase
      took place particularly in the non-lymphoid areas. Within the alpha beta TCR+ T
      cell population, both CD4+ T cells and CD8+ T cells were represented in
      proportions similar to those observed in normal uninfected mice. Stimulation of
      splenic T cells from infected mice with P. chabaudi-infected erythrocytes in
      vitro resulted in a blasted cell population composed predominantly of alpha beta
      TCR+ T cells with no preferential expansion of gamma delta TCR+ T cells. There
      was no evidence of superantigen-like stimulation of T cells bearing particular V
      beta chains of the TCR. The representation of the different V beta chains within
      the population was not significantly different from that seen in uninfected mice.

PMID- 8256110
TI  - T-cell stimulation induced by idiotypes on monoclonal immunoglobulins in patients
      with monoclonal gammopathies.
AB  - The stimulation of peripheral blood mononuclear cells by purified autologous
      and/or allogeneic monoclonal IgG was studied in five patients with multiple
      myeloma (MM), nine patients with monoclonal gammopathy of undetermined
      significance (MGUS) and six healthy individuals. Single cells secreting IFN-gamma
      or IL-2 were identified using an enzyme-linked immunospot assay. Patients' cells
      were preferentially stimulated by autologous monoclonal IgG at low concentrations
      (1-100 pg/ml), while 100 ng/ml or higher stimulated T cells both from patients
      and, to a lesser degree, healthy individuals. This biphasic dose-response of T
      cell stimulation by autologous monoclonal IgG was reproduced in all patients. The
      numbers of cells secreting IFN-gamma and IL-2 in response to allogeneic IgG were
      significantly lower than the numbers obtained using autologous IgG in patients
      with MM and MGUS. Cells from healthy individuals were stimulated by allogeneic
      monoclonal IgG, but to a lesser extent. The results of this study support the
      presence of idiotype-reactive T cells in patients with MM and MGUS and also may
      suggest a general but less pronounced T-cell reactivity to monoclonal IgG among
      these patients.

PMID- 8256111
TI  - 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen
      expression, accessory activity, and phagocytosis of human monocytes.
AB  - To investigate the differentiation and activation of monocytes, the combined
      effects of 1,25-dihydroxyvitamin D3 (D3) and IL-4 on human blood monocytes were
      examined with respect to expression of MHC class-II antigens, accessory activity,
      and phagocytic capacity. IL-4 was reported to upregulate the expression of MHC
      class-II antigens and accessory activity of monocytes. The experiments described
      here demonstrate that D3 inhibits the expression of all three subtypes of MHC
      class-II antigens (HLA-DR, -DP and -DQ) as well as the accessory activity of
      monocytes, both in a dose- and time-dependent manner. However, D3 enhances the
      immunoglobulin- and complement-dependent phagocytosis by monocytes in a dose- and
      time-dependent manner. When monocytes are treated with both IL-4 and D3, the
      effects of D3 are reverted by IL-4, suggesting that IL-4 induces the development
      of monocytes into accessory cells, whereas D3 stimulates differentiation of
      monocytes into classical macrophages. These findings provide further evidence for
      the contention that, depending on defined stimuli, monocytes may develop either
      into accessory cells or into classical macrophages.

PMID- 8256112
TI  - Redistribution of lymphocytes following E. coli sepsis.
AB  - Infusion of endotoxin elicits lymphopenia and a transient granulocytopenia
      followed by granulocytosis in peripheral blood. The purpose of this study was to
      investigate which tissues the lymphocytes are redistributed to in response to
      endotoxaemia. Lymphocytes were isolated from the peripheral blood of 20 rabbits,
      labelled with 111Indium-tropolene and reinjected intravenously into the rabbits.
      Ten rabbits received an infusion of Escherichia coli endotoxin 2 micrograms/kg-1,
      while 10 rabbits received isotonic saline and served as a control group. The
      redistribution of lymphocytes was imaged with a gamma camera, and calculated with
      an interfaced computer before, and 2, 4 and 6 h after infusion of endotoxin or
      saline. Interleukin-1 beta and serum cortisol were measured. Following
      endotoxaemia the lymphocytes in peripheral blood decreased from 1.95 10(9)/l to
      0.83 6 h later. Interleukin-1 beta and serum cortisol increased significantly.
      The radioactivity of labelled cells in the spleen and in the heart and lungs
      decreased to 83.3% and 87.8% of initial values respectively, 6 h after infusion
      of endotoxin. The radioactivity of the lymphatic tissue in and around the
      intestine increased to 128.8% of initial values. The results indicate that
      endotoxaemia induces redistribution of lymphocytes from peripheral blood and
      spleen to lymphatic tissue.

PMID- 8256113
TI  - Dermatitis herpetiformis--an autoimmune disease due to cross-reaction between
      dietary glutenin and dermal elastin?
AB  - Dermatitis herpetiformis (DH), is associated with skin eruptions and granular
      depositions of IgA in the papillary dermis, but this is not a feature of coeliac
      disease (CD). The specificity of the IgA in the skin is unknown. High molecular
      weight glutenin (HMW-g), a component of gluten, has been shown to have structural
      similarities to human elastin. This paper reports immunoadsorption studies which
      suggest that human serum may contain antibodies which cross-react with HMW-g and
      elastin. DH patients had significantly lower levels of IgA antibodies to HMW-g
      and to elastin than both CD patients and healthy controls. Furthermore,
      introduction of a gluten-free diet (GFD) was associated with a further reduction
      in the amount of IgA antibodies to elastin in the DH patients. This diet
      associated decrease of elastin antibodies was restricted to the IgA isotype. A
      significant correlation was observed between IgA antibodies to HMW-g and elastin
      in healthy controls and CD patients, while no such correlation was found in
      patients with DH. These findings could indicate that HMW-g induces production of
      antibodies to elastin, which are deposited in the skin, and that when the
      antigenic stimulus is removed, these antibodies are further reduced due to
      continuous dermal deposition. It is postulated that DH may be an autoimmune
      disease due to cross-reactivity between dietary glutenin and dermal elastin.

PMID- 8256114
TI  - IFN-gamma, IL-6 and IL-4 modulate M. leprae- or PPD-specific cytotoxic T cells in
      leprosy patients.
AB  - Specific cytotoxic T cells against intracellular pathogens may be generated in
      vitro. On the other hand it is well known that cytokines can regulate almost
      every aspect of immune function. The aim of this study was to evaluate the effect
      of some cytokines on the generation of cytotoxic T cells with specificity for
      Mycobacterium leprae- or PPD-pulsed autologous macrophages from leprosy patients
      and normal controls. Peripheral blood mononuclear cells from M. bovis BCG
      immunized controls or from leprosy patients were stimulated with antigen, in the
      presence or absence of cytokines, for 7 days. These were used as effector cells
      in a 4-h [51Cr]-release assay. Our results show that development of cytotoxic T
      cells may be enhanced by gamma-IFN, IL-6 or the combination of IL-6 and IL-2.
      Addition of IL-2 or TNF-alpha alone did not modify the generation of cytotoxic
      activity. IL-4 down-regulated the cytotoxic response and gamma-IFN was able to
      counteract this effect. Hence, the generation of specific cytotoxic T cells can
      be modulated by cytokines. Whether this cytotoxic mechanism contributes to
      protection or tissue damage in M. leprae infection remains to be determined.

PMID- 8256115
TI  - B cells carrying surrogate receptors in their membranes process and present
      antigen to specific murine T cells.
AB  - A palmitate-conjugate derivative of ovalbumin which can be inserted into the
      membrane of B cells has been prepared. The ability of these cells to act as
      antigen-presenting cells for specific T lymphocytes obtained from immunized mice
      was tested. It was found that the conjugates were more efficiently processed and
      presented than the naive form of the antigen. Palmitate-conjugated antibodies
      specific to ovalbumin were also inserted into the cell membrane of normal B
      lymphocytes. These cells were pulsed with the antigen and tested as antigen
      presenting cells for T cells obtained from immunized mice. The antibody-decorated
      B cells presented ovalbumin more efficiently than non-decorated controls. Whether
      antibody-decorated, antigen-pulsed B cells could prime T cells in vivo was
      investigated. Some priming activity was found.

PMID- 8256117
TI  - [Perioperative transesophageal echocardiography in heart surgery].
AB  - Transesophageal echocardiography (TEE) has proven to be a safe and useful method
      in open heart surgery. TEE allows the anesthesiologist to monitor global and
      regional ventricular function continuously and to optimize hemodynamic
      management. It offers the cardiac surgeon additional information and more safety
      with regard to planning and conduct of surgery as well as the possibility of
      immediate assessment of the surgical result. Correctly applied, TEE improves the
      overall quality of perioperative patient care.

PMID- 8256116
TI  - Okadaic acid, a phosphatase inhibitor, enhances the phorbol ester-induced
      interleukin-1 beta expression via an AP-1-mediated mechanism.
AB  - Protein kinase C (PKC)-activating phorbol esters are known to induce the
      expression of several genes in monocytic cells. As the effect of serine-threonine
      kinases, such as PKC, is often counteracted by specific protein phosphatases, we
      have now examined the role of phosphatases in the regulation of the phorbol ester
      (PMA)-induced interleukin-1 beta (IL-1 beta) gene expression in the THP-1
      monocytic leukaemia cell line. Okadaic acid (OA) is a potent tumour promoter, the
      function of which is based on its activity to inhibit the serine/threonine
      specific phosphatases 1 and 2A (PP1 and PP2A, respectively). Thus, it mimicks or
      potentiates the action of PKC activators in several cell types. Our data
      demonstrate that alone OA induced a very weak expression of IL-1 beta mRNA, but
      it strongly enhanced the PMA-induced IL-1 beta expression. To analyse the site of
      action of OA, the cells were transiently transfected with a chloramphenicol
      acetyl transferase (CAT)-reporter plasmid containing the AP-1 binding site as the
      enhancer. Alone, OA was a weak inducer of CAT-activity in these cells, but again
      it strongly enhanced the PMA-induced response. Similar data were obtained with
      cells transfected with a reporter plasmid containing the PMA-responsive element
      (containing a putative AP-1 binding site) of the IL-1 beta gene. Thus, these data
      indicate that the PMA-induced AP-1 enhancer activity, which is required for the
      expression of the IL-1 beta gene, is controlled in these cells by PP1 and/or
      PP2A. As OA did not synergize with PMA in the induction of expression of genes
      encoding the AP-1 proteins (c-fos, c-jun, junB), it is likely that OA potentiates
      the AP-1 enhancer activity by its effect on protein phosphorylation.

PMID- 8256118
TI  - [Role of transesophageal echocardiography in the diagnosis of cardiac disorders].
AB  - Transesophageal echocardiography provides a new window for ultrasound examination
      of the heart. The approach allows ultrasonic access to the heart in patients with
      transthoracic images of inadequate quality. Furthermore, transesophageal
      examination may provide information additional to that from the conventional
      transthoracic approach in the search for lesions including complications of
      endocarditis, mitral prosthesis dysfunction, aortic dissection, embolism of
      cardiac origin and selected cardiac malformations.

PMID- 8256119
TI  - An overview of intravascular ultrasound.
AB  - Intravascular ultrasound is a new technique based on the use of high-frequency
      transducers mounted in or on flexible catheters which can be inserted into
      arteries or veins. Although this technique is extremely promising for the
      evaluation or guidance of intravascular interventions, this application has yet
      to be proven conclusively. Intravascular ultrasound is already established as a
      research technique, especially for the evaluation of details of lesion size,
      morphology, or the results of interventions. Catheters can be divided into two
      principles of operation, mechanical or electronic. The mechanical systems can be
      further subdivided according whether the core, rotating element is fixed relative
      to the outside sheath, or can be moved. Interpretation of images requires
      knowledge of the histology of the arterial wall, as well as of the physics of
      ultrasound at high frequencies. Studies are now underway to assess the
      contribution of intravascular ultrasound to prognosis and outcome in
      interventional procedures.

PMID- 8256120
TI  - [Non-linear models for real time image processing and their applications in image
      enhancement, surface area determination and volume visualization].
AB  - This paper presents non-linear filter models that are suitable for real-time
      operations. The requirements imposed on these models by ultrasonic imaging are
      discussed. In particular, we study the characteristics of temporal filtering in
      cardiac imaging. Non-linear filter models incorporating these requirements are
      presented and compared with filtering schemes traditional in ultrasonic imaging.
      Furthermore, we illustrate how these filter models can be utilized to improve the
      quality and noise tolerance of automatic, real-time area detection algorithms.
      Finally, we present results from a 3D ultrasonic study of a foetus. The
      experiments illustrate how non-linear processing can increase the clinical
      information content that can be extracted from such investigations.

PMID- 8256121
TI  - [Digital processing and evaluation of ultrasound images].
AB  - With the help of workstations and PCs, on-site image processing has become
      possible. If the images are not available in digital form the video signal has to
      be A/D converted. In the case of colour images the colour channels R (red), G
      (green) and B (blue) have to be digitized separately. "Truecolour" imaging calls
      for an 8 bit resolution per channel, leading to 24 bits per pixel. Out of a pool
      of 2(24) possible values only the relevant 128 gray values and 64 shades of red
      and blue respectively needed for a colour-coded ultrasound image have to be
      isolated. Digital images can be changed and evaluated with the help of readily
      available image evaluation programmes. It is mandatory that during image
      manipulation the gray scale and colour pixels and LUTs (Look-Up-Table) must be
      worked on separately. Using relatively simple LUT manipulations astonishing image
      improvements are possible. Application of simple mathematical operations can lead
      to completely new clinical results. For example, by subtracting two consecutive
      colour flow images in time and special LUT operations, local acceleration of
      blood flow can be visualized (Colour Acceleration Imaging).

PMID- 8256122
TI  - [Signal processing in ultrasound imaging, Doppler and Doppler imaging].
AB  - The main purpose of signal processing in ultrasound imaging is the improvement of
      the image quality. The basics of three-dimensional, nonlinear image filtering are
      described in a simple way. For Doppler several million operations are computed
      per second to obtain the velocity distribution as a function of time. Various
      methods are described for overcoming the alias problem. For Doppler imaging the
      necessary computing power increases to several hundred million operations per
      second. Like other medical imaging methods, diagnostic ultrasound depends on
      powerful electronic computers.

PMID- 8256123
TI  - [Procedures in color Doppler ultrasound--comparison of methods].
AB  - Various colour flow imaging techniques for diagnostic ultrasound have been
      reported in the literature, each claiming distinctive performance characteristics
      for the benefit of the user. The following is a review of the principles of
      autocorrelation, autoregression (or maximum entropy), and of cross-correlation
      methods. All three approaches are based on the same principle of physics, i.e.
      the analysis of echoes backscattered from red blood cells of fluctuating density
      due to motion, but differ in their sampling requirements and in signal
      processing. A comparison of major performance features and challenges is given.

PMID- 8256124
TI  - [Significance of technical parameters in color-coded duplex ultrasound for
      vascular studies].
AB  - Reliable colour-coded ultrasound duplex investigations of the vascular system
      require sufficient knowledge of its technical features. The most important
      parameters are the emitted ultrasound frequency, the axial and lateral
      resolution, the relationship between the colour-coded and B-mode gain, the
      Doppler insonation angle of the vessels, the upper (aliasing threshold) and lower
      (wall filter) cut-off frequencies, the frame rate as well as the influence of
      digital image processing. The practical relevance of these features for assessing
      the velocity, direction, pulsatility, localisation and disturbance of flow in
      blood vessels is discussed in comparison to conventional Doppler and duplex
      techniques.

PMID- 8256125
TI  - [Determination of the length of the occlusion in extremity arteries--color duplex
      ultrasound versus angiography].
AB  - In the management of patients with peripheral arterial occlusive disease the
      length and location of an arterial occlusion has an impact on the choice of the
      method of arterial reconstruction, i.e. percutaneous transluminal angioplasty or
      vascular surgery. The aim of this study was to determine the accuracy of colour
      coded Doppler sonography (CDS) compared to conventional contrast arteriography in
      detecting the length and localisation of an occlusion in peripheral arteries. 100
      legs of 94 patients (27 women, 44 to 82 years of age [mean 60.9 years] and 67
      men, 21 to 78 years of age [mean 61.3 years]) with clinically suspected artery
      occlusion were examined prospectively with CDS before angiography and
      angioplasty. The exact localisation was correctly diagnosed by CDS in 95% with a
      high correlation (r = 0.95) of occlusion length between both methods. The
      sensitivity in detecting occlusions was 98% (positive predictive value 98%). It
      is concluded that colour-coded Doppler sonography can diagnose the length and
      location of an occlusion in peripheral arteries accurately and therefore can be
      used as a noninvasive method to select patients for further therapy management.

PMID- 8256126
TI  - Gastrocolic fistula-secondary to aspirin abuse.
AB  - Gastrocolic fistula is a rare complication of benign gastric ulcer disease. It
      has been associated more commonly, in the past, with marginal ulceration
      following gastrojejunostomy for peptic ulcer disease. We will describe a classic
      case of gastrocolic fistula as a complication of acetylsalicylic acid abuse in a
      middle aged female with a remote history of aspirin induced ulcer. Her
      presentation was classic and required a surgical approach with excellent
      recovery. We will describe the clinical, radiographic, endoscopic and surgical
      aspects of this interesting and unusual disorder.

PMID- 8256127
TI  - Rural health care networks in South Dakota.
AB  - To address health care access concerns, a Regional Coordinated Care Network
      (RCCN) program, through Robert Wood Johnson Foundation Practice Sights Initiative
      funding, is being developed by the South Dakota Office of Rural Health. The
      intent of the initiative is to expand primary and preventive care and, hopefully,
      permanently reduce the number of Health Professional Shortage Areas (HPSAs) in
      the state by linking and enhancing providers and services. In rural areas such
      networking will be crucial for the delivery of health care. Surely, the impact on
      family physicians will be significant and salutary.

PMID- 8256128
TI  - DEEP, the South Dakota Medicaid drug use review program. Is the hassle justified?
AB  - Governmentally-mandated programs are a fact of life in health care. Such programs
      are often considered "hassles" by health care providers, who sometimes question
      whether such programs can justify themselves. The South Dakota Drug Evaluation
      and Education Program (DEEP) is a federally-mandated program of drug use review
      for Medicaid patients. While the program does not mandate changes in therapy,
      review of the program's first year of data indicates it caused change in 68.1% of
      the cases resulting in benefits which include a reduction in unnecessary/unneeded
      medication.

PMID- 8256129
TI  - What their caregivers don't know may hurt them.

PMID- 8256130
TI  - Perspectives on drug interactions.

PMID- 8256131
TI  - Health care reform--SoDaPAC.

PMID- 8256132
TI  - From school without walls to library without walls--continued medical progress on
      the wide open plains!

PMID- 8256133
TI  - Postintubation tracheal stenosis: diagnosis and management.
AB  - Postintubation damage is a potential hazard in any patient intubated with an oral
      or nasal endotracheal tube or with a tracheostomy tube for ventilatory support.
      Postintubation tracheal stenosis may be fatal unless it is recognized and treated
      promptly. This paper reviews the important features of diagnosis and treatment of
      postintubation tracheal stenosis.

PMID- 8256134
TI  - Carcinoma of the extrahepatic bile duct.
AB  - We present a case of a 70-year old American Indian who had a previous
      cholecystectomy for symptomatic cholelithiasis and who presented, one year later,
      with progressive painless jaundice and a dilated common bile duct. Work-up
      revealed an adenocarcinoma of the extrahepatic bile duct. In this article we
      discuss the common presentation, work-up, and treatment of carcinoma of the bile
      ducts.

PMID- 8256135
TI  - Physicians and health care reform--a perspective.

PMID- 8256136
TI  - Scintigraphic evaluation of the growth plate.
AB  - Multiphase bone scintigraphy is used to assess growth plate function in the
      growing skeleton. It can identify an evolving total or segmental closure by
      comparing an affected plate with a contralateral normal plate. Although visual
      interpretation is usually adequate, quantitative methods permit a more objective
      assessment. Total or partial closure occurs in response to trauma and infection;
      plate closure also may be induced surgically to prevent progressive leg length
      inequality. As new orthopaedic procedures for correcting early plate closure are
      developed, the need for accurate physiological assessment of the growth plate is
      critical.

PMID- 8256137
TI  - A scintigraphic classification of Legg-Calve-Perthes disease.
AB  - The onset of Legg-Calve-Perthes (LCP) disease, avascular necrosis of the proximal
      femoral epiphysis, frequently is clinically undetectable for months before
      presentation. This traditional X-ray methods of diagnosis are insensitive for the
      diagnosis of early LCP as well as nonspecific for the diagnosis of advanced LCP.
      The X-ray may remain normal for weeks to months after the onset of LCP, and other
      disorders (steroid osteopathy, epiphyseal dysplasia) simulate the X-ray
      appearance of LCP during its later stages. Localization of bone-avid
      radiopharmaceuticals depends principally on bone perfusion and metabolism. Bone
      scintigraphy is a highly sensitive and specific means of detecting changes in
      bone perfusion. An understanding of the vascular anatomy of the pediatric hip and
      its revascularization mechanisms is essential for correlating the scintigraphic
      findings with the stages of healing in this disorder. Revascularization of bone
      can occur by recanalization of existing vessels or by neovascularization through
      the development of new vessels. Recanalization is a rapidly occurring process
      (minutes to weeks), whereas neovascularization is a prolonged process (months to
      years). The recanalization process has a characteristic scintigraphic pattern
      beginning with the visualization of a "lateral column" and is associated with a
      good prognosis for eventual outcome in LCP. Neovascularization also has a
      characteristic scintigraphic appearance ("base filling" and "mushrooming"), which
      is associated with a poorer prognosis because of the prolonged interval required
      for healing, which places the femoral head at risk for complications such as
      fracture, collapse, and extrusion. The scintigraphic staging classification
      presented here, when correlated with a modified Waldenstrom X-ray staging,
      readily differentiates three mechanisms of revascularization. The A (allright)
      track scintigraphic pattern represents the recanalization process, a process of
      short duration and good prognosis. The B (bad) track scintigraphic pattern
      represents the process of neovascularization, a process of long duration and
      poorer prognosis. A third process also is described in which complications of the
      healing process (collapse, extrusion), particularly during the reabsorptive
      phases of bone reconstitution when the bone is weakened, can cause conversion
      from track A to track B. Bone scintigraphy is useful in LCP for its ability to
      detect the disorder in its initial stages, thus allowing earlier treatment, and
      to provide prognostic information that may affect therapy.

PMID- 8256138
TI  - Spine pain in children.
AB  - Spine pain in children as an isolated symptom is infrequently seen in clinical
      practice. However, as opposed to spine pain in adults, it is accompanied by a
      relatively higher frequency of pathology. Diagnostic imaging is a necessary
      follow up to the physical examination and laboratory studies. Standard
      radiography is usually the initial imaging study. Frequently, however, additional
      imaging with bone scintigraphy, computed tomography, or magnetic resonance
      imaging is necessary to add sensitivity and specificity to the clinical
      presentation. We describe the disease entities, pathophysiology, and imaging
      characteristics of the varied pathologies responsible for spine pain in children.

PMID- 8256139
TI  - The role of bone scintigraphy in detecting child abuse.
AB  - This review of diagnostic imaging in cases of suspected child abuse characterizes
      the significant differences between bone scintigraphy and x-ray evaluation,
      describes the advantages and disadvantages of each modality, postulates on the
      specific mechanisms of injury that produce the characteristic scintigraphic
      findings, and emphasizes the influences that scintigraphic studies have on the
      medical, social, and legal aspects of child abuse. The major advantages of bone
      scintigraphy are its increased sensitivity (25% to 50%) in detecting evidence of
      soft tissue as well as bone trauma in child abuse. Furthermore, it is postulated
      that the specific mechanisms of inflicting the trauma relate to the patient's
      size and are characterized by bone scintigraphy. During fits of anger or
      frustration, the perpetrator of child abuse grasps the small infant or child by
      the thorax during the shaking activity. This produces characteristic rib
      injuries. The older and heavier child is more likely to be grabbed by the
      extremities, which produces periosteal injuries manifested as characteristic
      abnormal localizations in the diaphyses of the extremities. The roentgenograms of
      these injuries are frequently normal. The importance of bone scintigraphy is its
      complementary nature in defining and characterizing the extent and severity of
      trauma from child abuse. Such findings have direct bearing on the medical,
      social, and legal outcomes for the abused child. The quality of scintigraphic
      imaging is important, requiring the use of magnification techniques in the
      infant. The interpretation of the scintigraphic images depends on an
      understanding of the mechanisms by which the radionuclide localizes in bone. The
      same traumatic incident can lead to decreased, normal, or increased localization
      at the trauma site. Radionuclide scintigraphy is a complementary rather than
      competitive imaging modality to X-ray evaluation in the diagnosis and management
      of physical child abuse.

PMID- 8256140
TI  - A multiscintigraphic approach to imaging of lymphedema and other causes of the
      congenitally enlarged extremity.
AB  - Nuclear imaging in the definition of the components of the congenitally enlarged
      extremity is important in the design of a successful therapeutic regimen. In our
      series of 32 patients evaluated for primary lymphedema, 85% were determined to
      have abnormalities that were not purely lymphatic in origin. The
      multiscintigraphic approach defines the components of the lymphatic and vascular
      systems with the use of technetium-99m [99mTc] antimony sulfide colloid (99mTc
      Sb2S3) for lymphatic, 99mTc diethylenetriamine pentacetic acid (DTPA) for
      capillary-interstitial, and 99mTc-tagged red blood cells for venous systems.

PMID- 8256141
TI  - Chronic child neglect in perspective.
AB  - Although the concept of chronic neglect is used in child welfare practice,
      studies have not differentiated chronic cases of neglect from those of more
      recent onset. In this study three groups of families referred to a large
      metropolitan county child welfare agency for child neglect are considered: those
      known to the agency for three years or more (chronic group), those more recently
      referred and substantiated (newly neglecting group), and those in which neglect
      was not substantiated (unconfirmed group). Significant differences among the
      three study groups included family size and composition, numbers and kinds of
      problems, neighborhood characteristics, family relationships, parenting knowledge
      and expectations, and mental health. Findings demonstrate the need for changes in
      social policy and social services delivery systems to supplement intervention
      with individual families.

PMID- 8256142
TI  - Empowerment and self-help agency practice for people with mental disabilities.
AB  - During the past 15 years, there has been tremendous growth in the number of self
      help groups and agencies for mental health clients. This article examines the
      self-help perspective in relation to problems with traditional mental health
      services and the need for client-run services. Self-help agencies see their goal
      as empowerment on an individual, organizational, and societal level. They strive
      to accomplish this by helping members obtain needed resources and develop coping
      skills; providing means of enhancing members' self-concept and lessening the
      stigma of perceived mental disability; giving members control in the agencies'
      governance, administration, and service delivery; and furthering member
      involvement in social policy-making. The goal of this article is not to endorse
      the self-help perspective but to use it as the basis for raising research
      questions that will further the mental health practitioner's understanding of
      this service modality.

PMID- 8256143
TI  - Discharge planning revisited: what do social workers actually do in discharge
      planning?
AB  - The professional literature reflects a lack of clarity regarding the activities
      performed in discharge planning. Does discharge planning primarily focus on the
      provision of concrete services, counseling, or both? Within a structured
      interview format, 80 social workers in 36 acute care hospitals were asked to
      estimate the amount of time they spent on and the importance of 73 discharge
      planning tasks. Respondents were also asked to locate themselves on an activity
      continuum. The survey results are discussed in terms of the prospective payment
      system's emphasis on expeditious discharge and the challenge to social workers in
      enabling patients and families to have some control over decision making in this
      climate.

PMID- 8256145
TI  - Understanding death and grief for children three and younger.
AB  - Although the average toddler's cognitive skills may be limited, children three
      and younger have emotional responses to the death of someone they have known.
      Theories and research indicate that children's individual characteristics, their
      developmental stage including cognitive level, and their environmental and
      familial experiences must be considered to understand their grief. Myriad
      misconceptions and euphemisms can complicate and exacerbate children's grief. The
      authors address the possibilities for age-appropriate, theory-based interventions
      by clinicians and parents to effectively assist children three and younger in
      their grief work.

PMID- 8256144
TI  - Research strategies for consumer empowerment of people with severe mental
      illness.
AB  - Research concerning the care and treatment of people with severe mental illness
      has not been consonant with the well-established emphasis on consumer empowerment
      in social work and the psychiatric rehabilitation field. This article provides a
      set of research strategies that would help bridge the gap. We argue that research
      should amplify "the voice of the consumer" by attending to the context of
      research, the vantage point, the process of formulating research questions, the
      selection of interventions to be tested, the selection of outcomes and measures,
      and the dissemination of research results.

PMID- 8256146
TI  - Families with children with emotional disorders: a review of the literature.
AB  - This review identifies and explores a body of literature that correlates a
      child's emotional or behavioral problems with some aspect of the family and a
      body of literature that considers a wider ecological perspective. This literature
      is examined in relation to two questions: (1) What do we know about families with
      children with emotional disorders? and (2) How does that information help us
      design social policy and social work interventions for these families and their
      children? The hope for social work research and practice, as well as program and
      policy development, lies in expanding the ecological work that considers factors
      related to children's referral for mental health services, parents' perspectives
      of what they expect from mental health services, and parents' perspectives of
      their experiences and needs in relation to their child with emotional or
      behavioral problems.

PMID- 8256147
TI  - [Volvulus of the cecum].
AB  - The authors present a group of seven patients treated at the First Surgical
      Clinic of the Faculty Hospital Olomouc on account of volvulus of the caecum
      during the period between 1963 and 1992. Based on their own experience which is
      consistent with results reported in the literature, the authors discuss the
      problem of diagnosis and optimal treatment of volvulus of the caecum.

PMID- 8256148
TI  - [Stab and gunshot thoracoabdominal injuries].
AB  - The authors give an account of their experience with the treatment of punctures
      and gunshot injuries of the chest and abdomen in 43 patients hospitalized at the
      Surgical Clinic of the Third Medical Faculty, Charles University Prague 10
      between 1989 and 1992. Injuries of the chest were recorded 15 times, abdominal
      injuries in 25 patients and concurrent injuries of the chest and abdomen in three
      patients. To ensure treatment of penetrating injuries the authors present an
      algorithm which comprises differentiated care as well as some non-interventional
      diagnostic methods (ultrasonography, computed tomography). Based on analysis of
      their own results and data in the literature, the authors recommend in casualties
      with penetrating chest injuries and abdominal injuries early indicated surgical
      revision which alone ensures adequate treatment with minimal diagnostic errors.
      They also draw attention to the necessity to ensure effective first aid and rapid
      transport of casualties to prevent the development of irreversible changes as a
      result of haemorrhage, as observed in a single patient who died after a piercing
      heart injury.

PMID- 8256149
TI  - [Laparoscopic resection of the sigmoid].
AB  - The authors present their own experience with laparoscopic resection of the
      sigmoid colon. They discuss the technique, the postoperative course and the
      contribution of this new method.

PMID- 8256150
TI  - [Prophylactic and therapeutic use of Avrazor in abdominal surgery].
AB  - The authors investigated in a group of 30 patients the prophylactic and
      therapeutic action of ornidazole (the Czech preparation Avrazor) injections for
      infusion produced by Leciva Co. Prophylactically Avrazor was used most frequently
      in elective colorectal surgery, therapeutically in peritonitis. In a control
      group comprising 30 patients with the same indications the commonly used
      Metronidazole was administered and the results in the two groups were compared.
      Avrazor was administered most frequently combined with aminoglycosides. The
      authors did not observe side-effects after Avrazor administration and the
      preparation was very well tolerated. Because of its antimicrobial effect in the
      prophylaxis and therapy of intraabdominal infections the preparation can be
      recommended for clinical use.

PMID- 8256151
TI  - [Can the system for ordering blood for elective surgery be improved?].
AB  - The authors investigated the effectiveness of ordering of blood for elective
      surgery. Analysis of a group of 333 operated patients revealed that blood was
      administered only in 9% of the operations, i.e when compared with the number
      ordered the ratio ordered: issued was 13:1. Based on their own experience the
      authors present the possibility how to improve the blood ordering system from the
      surgical as well as blood bank activity aspect.

PMID- 8256152
TI  - [Arterial embolization in the care of massive hemorrhage from the rectum].
AB  - Haemorrhage from distal parts of the GIT is as a rule associated with diagnostic
      and therapeutic difficulties, in particular when massive haemorrhage is involved.
      The authors describe a group of three patients where the source of haemorrhage
      was an inoperable rectal tumour. This problematic condition was successfully
      treated by embolization of the upper rectal artery.

PMID- 8256153
TI  - [The Lichtenstein "tension free" operation for inguinal hernia].
AB  - The authors present their experience with operations of 264 inguinal hernias in
      238 subjects where Lichtenstein's technique was used. The principle of the
      operation is reconstruction of the posterior wall of the inguinal canal by means
      of a synthetic mesh-tension free. The attained results in this group (L) were
      compared with a control group of 68 operated patients (group C) where the
      classical McVaye technique was used. They did not find a difference in the time
      taken up by the operation or the time of hospitalization. The postoperative
      mortality was 0.4% in group L and 2.9% in group C, the morbidity was 15.5% and
      42.6% resp. So far they did not record a case of relapsing hernia or rejection of
      the mesh. The operation is easy to perform, economically unpretentious, the
      postoperative pain is milder and the sensation of discomfort slighter than after
      the classical operation. With regard to the assembled experience, the authors
      recommend the new operation not only in inguinal but also other types of hernias
      where tension free repair is impossible. For reconstruction they use polyester
      mesh CHS 100 manufactured by the Hosiery Research Institute in Brno.

PMID- 8256154
TI  - [Cardiac complications in patients after elective pelvic reconstruction in
      ischemia of the lower extremities].
AB  - The authors investigated the incidence of cardiac complications in patients after
      elective pelvic reconstructions on account of ischaemic disease of the lower
      extremities in 1985-1990 and in 1990-1993. The first group of patients was
      examined by an experienced internist and the second by a cardiologist. The second
      group had a substantially higher percentage of risk factors than the first one.
      In the first group the postoperative cardiac morbidity was 3.4 and the mortality
      2.1%. In the second group of patients both morbidity and mortality were 2.7%. The
      mortality quoted in the world literature is lower than 3%. The authors emphasize
      the necessity of comprehensive preoperative examination of patients indicated for
      pelvic reconstruction, perfect surgical technique and anaesthesia provided by an
      anaesthesiologist with experience with patients suffering from vascular diseases.
      It is very important to monitor rheological parameters in patients during the
      postoperative period immediately after surgery.

PMID- 8256155
TI  - [Aggressive fibromatosis in the extremities].
AB  - The authors demonstrate in a group of 10 patients treated in the course of 15
      years the rare incidence of aggressive fibromatosis of the extremities and the
      large number of relapses after surgery. They also emphasize the necessity of
      detailed preoperative examination, priority of a surgical approach, as compared
      with radiotherapeutic procedures, and the possibility of skeletal and vascular
      reconstruction after radical surgery.

PMID- 8256156
TI  - [Retroperitoneal fibrosis in children].
AB  - The authors describe retroperitoneal fibrosis (RPF) in general and the case of a
      six-year-old child who suffered from RPF. Due to the atypical course of the
      disease the diagnosis was very difficult not only due to the clinical course but
      also because of the histological examination. The atypical course was manifested
      by affection of the lungs, liver, pancreas and porta hepatis. The urinary system
      was also affected by the fibrotic disease. The authors reached the conclusion
      that in an atypical course of the disease only repeated biopsy is decisive for
      establishment of the diagnosis.

PMID- 8256157
TI  - [A multidisciplinary approach in the treatment of endocrine orbitopathy].
AB  - Despite the knowledge of immunological mechanisms of Graves-Basedow's disease the
      pathogenesis of endocrine orbitopathy remains obscure. Apart from the most
      frequent association with GB disease it may occur also in patients with primary
      hypothyroidism, Hashimoto's thyroiditis or in rare instances in euthyroid
      patients not suffering from thyroid disease. Endocrine orbitopathy is a typical
      example of a disease with a multidisciplinary approach to its diagnosis and
      treatment. In the submitted paper the authors demonstrate the collaboration of
      four clinics of the Faculty Hospital when dealing with this problem. Complete or
      almost complete removal of the thyroid gland leads within 1-4 years to regression
      of the protrusion of the bulbus by 1 mm. In combination with decompression of the
      orbit by a modification of Ogura's and Walsh's method improvement of visual
      acuity by 50% was achieved and the mean value of the exophthalmus diminished by
      3.5 mm.

PMID- 8256158
TI  - [Surgical treatment of thoracic empyema].
AB  - During the seven-year period from 1986-1992 85 patients with a purulent process
      in the pleural cavity were treated. The author classifies the disease by its
      aetiology and mentions different surgical approaches. Treatment was successful in
      the group of pneumonic empyemas and the author mentions also the marked decline
      of empyemas after resections of the lungs during the last three years.

PMID- 8256159
TI  - [Initial experience with videothoracoscopy].
AB  - In the course of five months the authors made 32 videothoracoscopies. They
      consider this surgical operation as a completely new quality in thoracic surgery.
      The hitherto limited scope of these examinations will, no doubt, expand as a
      result of the assembled experience.

PMID- 8256160
TI  - [Initial experience with a new silicone drain made by Rubena Nachod].
AB  - At the Surgical Clinic in Plzen in 1992 clinical trials were made to test drains
      manufactured in Rubena Nachod (plant in Velke Porici). These soft silicone X-ray
      contrasting drains were used in 40 patients. A total of 70 drains were used, all
      in abdominal operations incl. acute abdominal surgery and injuries. The mean
      drainage period was 9.2 days, the longest period was 38 days. In all instances
      the drainage was effective, none of the patients developed a residual abscess or
      intestinal fistula. The material from which the drains are made was well
      tolerated by all patients and none of them developed a reaction.

PMID- 8256161
TI  - [Initial experience with the use of fibrin glue in clinical surgery].
AB  - The use of tissue glue has been extended to all parts of surgery. There is not
      much experience in its application in this country. The report deals with the
      first clinical results of its use on various indications in general,
      traumatological, thoracic, vascular and pediatric surgery. A total of 100
      patients were investigated. The fibrin system was found to be reliable, effective
      and safe. A successful use was noted in 88%, unsuccessful in 12% and
      complications occurred in 4%. Differences in success were statistically important
      in various indications. Special attention was given to serious complications that
      must be avoided.

PMID- 8256162
TI  - [Rheumatoid arthritis and microbial infection: a review].

PMID- 8256163
TI  - [Clinical study of Still's disease as a distinct disease entity].
AB  - There seems to be yet unresolved questions as to whether child-onset and adult
      onset Still's disease are truly the same disease and whether adult-onset Still's
      disease is a disease entity independent of other rheumatic diseases in the adult.
      In order to clarify these issues, we have analyzed statistically the clinical
      features of Still's disease of various age-onset and also compared the features
      of adult-onset Still's disease with those of other rheumatic diseases having
      similar manifestations. Clinical data used for the study were those collected
      from 32 institutions in Japan through questionnaire method by Adult Still's
      Disease Research Committee, and the patients with adult Still's disease and with
      other rheumatic diseases were definitely diagnosed by the Committee. When the
      sensitivity of each of total 90 clinical items was compared between child-onset
      adult Still's disease (11 cases) and adult-onset Still's disease (77 cases), and
      between young adult-onset (16-35 years) Still's disease (48 cases) and aged adult
      onset (45 years or older) Still's disease (15 cases), only 7-9% of the items
      showed significant difference by chi 2-test. This was the same range as when the
      sensitivity of the clinical items obtained from the literature of child-onset
      Still's disease (26 cases) was compared with that of adult-onset Still's disease
      (77 cases). On contrary to this range, over half of the items showed the
      significant difference in sensitivity when adult-onset Still's disease was
      compared with other rheumatic diseases such as seronegative rheumatoid arthritis
      (31 cases), malignant rheumatoid arthritis (25 cases), and polyarteritis nodosa
      (31 cases).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256164
TI  - [Plasma coagulation and fibrinolysis parameters in patients with vascular
      Behcet's disease, and analysis of the multimeric structure of von Willebrand
      factor (vWF)].
AB  - We studied the relationship between vascular complications and coagulation and
      fibrinolysis parameters in ten subjects with Behcet's disease. We found that
      patients with Behcet's disease were in a state of hypercoagulation and
      hyperfibrinolysis. In vascular Behcet's disease in particular, coagulation and
      fibrinolysis parameters appeared to be indices of vascular complications.
      Analysis of the multimeric structure of von Willebrand factor (vWF) revealed a
      tendency for large multimer of vWF to increase in patients with Behcet's disease
      with accompanying vascular complications, whereas such increase were not observed
      in patients with Behcet's disease without any vascular complications. Therefore,
      analysis of vWF multimeric structure and the determination of coagulation and
      fibrinolysis parameters in plasma appear to be useful indicators of vascular
      complications in Behcet's disease.

PMID- 8256165
TI  - [Osteolytic and osteosclerotic lesion of the femur associated with pustulosis
      palmaris plantaris].
AB  - The cases with pustulosis palmaris et plantaris associated with lesions in sterno
      cost clavicular region, spine and ilio sacral joint have been in the previous
      literatures. We encountered four rare cases of this pustulosis in association
      with femoral lesion. We mainly reported their radiological and pathologic
      findings. Three cases had lesions in the diaphysis of the femur, while one case
      had lesion in the lesser trochanter. The average age was 55.5 years (range 53-60)
      All patients complained of thigh pain. Three cases suffered sterno cost
      clavicular pain also. Laboratory data showed the elevation of white blood cell
      number, ESR and tested positive for C-reactive protein. The radiological findings
      showed osteolytic lesions of the femoral cortex at the onset of the disease,
      followed by thickening and sclerosis in the cortex. A biopsy was performed in
      three cases and the pathological results showed no malignancy. The specimens
      showed only chronic inflammation. Pathological results and radiological
      abnormalities suggested that femoral lesion of pustulosis palmaris et plantaris
      originated from the periostenum or the cortex of bone.

PMID- 8256166
TI  - [Development of Stevens-Johnson syndrome following sulindac administration in a
      patient with mixed connective tissue disease].
AB  - Nineteen-year-old woman with mixed connective tissue disease developed Stevens
      Johnson syndrome following treatment of arthritis using sulindac. Involvements of
      infectious and malignant diseases have been ruled out and sulindac has strongly
      been suspected as a causative agent for Stevens-Johnson syndrome. Ten out of 13
      cases with Stevens-Johnson syndrome associated with non-steroidal anti
      inflammatory drugs, sulindac has been administrated. Four cases also presented
      with severe liver disease. Patients who developed Stevens-Johnson syndrome
      following sulindac administration did not have apparent common clinical or
      laboratory findings which might be implicated for development of this severe side
      effects. Among the various non-steroidal anti-inflammatory drugs, safety of
      sulindac has widely been appreciated. However, occurrence of severe adverse
      events as reported here indicated that sulindac should be administrated as
      carefully as other non-steroidal anti-inflammatory drugs.

PMID- 8256167
TI  - [Autoimmune and collagen disease manifestations in HIV infection or AIDS].

PMID- 8256168
TI  - [Collagen diseases and fever of unknown origin].

PMID- 8256169
TI  - [Guidelines for the diagnosis of rheumatic fever: Jones criteria, updated 1992].

PMID- 8256170
TI  - Bringing it home: Israeli social workers implement leadership program values.
AB  - To date, ten Israeli senior social workers have graduated from the Mount Sinai
      Leadership Exchange Program. This report describes the impact of the program on
      the activities back home of the first six graduates, two of whom had graduated in
      1989, two in 1990, and two in early 1991. The report evaluates the outcomes of
      the exchange program in terms of change in the graduates' knowledge, attitudes,
      and beliefs, and in their actions within their organizations and at a national
      level.

PMID- 8256171
TI  - Bringing it home: Australian social workers implement leadership program values.
AB  - Two senior social workers from major teaching hospitals in Adelaide, South
      Australia, were the first participants from Australia in Mount Sinai's leadership
      exchange program, from November 1, 1990 to January 31, 1992. The two participants
      were eager, excited, and strongly committed to participating fully in the
      project. They left Australia with the intent to bring back new skills, insights,
      and vision--for themselves, their hospitals, and the social work profession. They
      returned with advanced skills and insights and remarkably altered attitudes
      toward research, writing for publication, their relationship with academia,
      leadership and management, the development of innovative programs, and
      information systems. And, they returned with a clear international perspective of
      their profession, its uniqueness and its opportunities.

PMID- 8256172
TI  - A personal-professional re-view of the leadership enhancement program.

PMID- 8256173
TI  - Enhancing leadership skills through an international exchange: the Mount Sinai
      experience.
AB  - The development of an international social work educational exchange between
      Mount Sinai Medical Center and key social workers in health care organizations in
      Israel and Australia supported the notion that western social workers from
      different parts of the world, facing comparable social-health problems, can learn
      from each other, but only if ideas and "methodologies are selectively adapted"
      (Midgley, 1990, p. 297) to allow for regional and cultural differences. When
      objectives are comparable, content and experiences can be shared, and knowledge
      and practice can be adapted to meet social-health needs of given populations,
      within the context of respective government policies and expectations.

PMID- 8256174
TI  - Chemical warfare: disaster preparation in an Israeli hospital.
AB  - The situation in the Middle East makes it imperative that Israeli hospitals be
      prepared for disaster, particularly that associated with chemical warfare. To
      prepare for the impact of chemical warfare, Israeli hospitals have designed mass
      trauma programs, which include staff training and simulated disaster drill
      exercises. These have been incorporated in the conventional disaster program
      since 1989. This article provides a brief overview of the trauma program at
      Beilinson Medical Center in Petach Tikva, Israel, including definition of four
      stages of injury, guidelines for intervention, and a discussion of the role of
      the social worker in the disaster plan.

PMID- 8256175
TI  - Disaster preparation and the functioning of a hospital social work department
      during the Gulf War.
AB  - The nature of the Gulf War and its consequences for the public at the personal
      and community levels, called for considerable alterations in organization and
      management at the Chaim Sheba Medical Center, the largest government general
      hospital in Israel, with constant adaptation to the changing situation. The
      preparations and exercises preceding the state of emergency, combined with the
      knowledge and experience gained in similar situations in the past, equipped the
      staff of the Social Work Department to function adequately and to make
      appropriate decisions and changes in the face of moral and ethical dilemmas, as
      well as immediate physical threat. This article presents the rationale for the
      model of intervention that guided the hospital during the Gulf War in offering
      services to casualty victims and their families. Also discussed are the process
      of developing an organizational framework and its content that meets wartime
      demands, and the implications for social work practice in dealing with a war
      crisis.

PMID- 8256176
TI  - Emergency room: individuals, families and groups in trauma.
AB  - Each year in Israel hundreds of people lose their lives in road accidents; many
      more are injured (Field Staff, 1986). The effect on families, on hospital staff,
      and even on whole communities can be debilitating. Recognizing the grave impact
      of trauma and its aftermath, the Haemak Medical Center, Afula, established an
      emergency/trauma program in 1986. The program was developed by the Department of
      Social Work Services, with the cooperation of the emergency room (ER) team. Based
      on meetings with and preparation of the ER team (physicians, nurses, and social
      work staff), the department developed a protocol for integrating social workers
      and psychosocial concepts into the emergency/trauma situation.

PMID- 8256177
TI  - Rape crisis: development of a center in an Israeli hospital.
AB  - The Social Work Department at B'nai Zion Medical Center in Haifa, Israel worked
      with health care professionals within the hospital and in community organizations
      to establish a rape crisis center in the emergency room. The department developed
      procedures, guidelines, and protocols for the center; developed and conducted
      training seminars for hospital and community organization staff; and created a
      plan for crisis intervention.

PMID- 8256178
TI  - Termination of pregnancy: development of a high-risk screening and counseling
      program.
AB  - The Social Work Department of The Queen Elizabeth Hospital in Adelaide, South
      Australia, developed a social work service for women presenting for elective
      termination of pregnancy. They used a high social risk identification and
      screening process and developed a protocol describing essential elements of the
      clinical social work practice. Program development was practice-based and
      empirical, using practice experience and drawing from relevant literature.

PMID- 8256179
TI  - Respite care in a geriatric rehabilitation hospital: a support system for
      caregivers of disabled elderly.
AB  - Respite care is one of a wide range of services designed to help maintain the
      infirm elderly at home by reducing the burden on the caregiver. The availability
      and results of respite care may alter decisions to institutionalize an elderly
      relative. Fliman Hospital, a geriatric rehabilitation hospital in Haifa, provides
      short-term, inpatient care for bedridden frail or disabled elderly persons living
      in the community with the support of an informal network.

PMID- 8256180
TI  - Teaching bedside interviewing skills in a social work training program.
AB  - Teaching interviewing skills has become a permanent feature of the training of
      social workers, although no standardization exits for interview training. At a
      learning center established through a collaborative effort between Haifa
      University and the Kupat Holim, an effective program for teaching bedside
      interviewing skills was established.

PMID- 8256181
TI  - A call for international exchange among social work leaders.

PMID- 8256182
TI  - Social work leadership development through international exchange.
AB  - Social workers in large bureaucratic settings face the pressure to define their
      service in relation to other professional disciplines and to maintain a quality
      service despite conflicting mandates and economic restraints. Few strategies
      exist for providing training and education to senior social workers in order to
      help them develop leadership roles in multidisciplinary environments. This paper
      examines the characteristics and qualities necessary to provide social work
      leadership in a complex hospital environment. The ideas emerged from an
      international leadership exchange program with The Mount Sinai Medical Center in
      New York City. Aspects of this experience are used to illustrate leadership
      roles.

PMID- 8256184
TI  - Proxy law in New York State and Victoria, Australia: a social work perspective.
AB  - Both the State of New York and Victoria, Australia, have enacted health care
      proxy legislation in the past two years. The provisions are similar, although
      there is some difference in detail. This article reviews and compares the health
      proxy laws in each of these two states.

PMID- 8256183
TI  - Australia: its land, its people, its health care system, and unique health
      issues.

PMID- 8256185
TI  - Evaluating the Mount Sinai Leadership Enhancement Program: a developmental
      perspective.
AB  - The principal evaluators of the Mount Sinai Leadership Exchange program used a
      developmental approach to evaluating the program, applying qualitative and
      quantitative data within the program as the program developed. Over the course of
      its development, evaluation, and refinement, the leadership enhancement program
      emerged as a vehicle for true international exchange of ideas, skills, resources,
      and collegiality.

PMID- 8256186
TI  - A critical analysis of recent innovations in the treatment of intra-abdominal
      infection.
AB  - Toward the end of the last decade, clinical trial results in the surgical
      literature reported a major improvement in survival from serious intra-abdominal
      infection. Mortality rates for certain complex infections, such as necrotizing
      pancreatitis and postoperative abscess, decreased by almost 50 percent when
      compared with both hospital controls and the predicted mortality rate according
      to severity of illness (1-3). This remarkable improvement in outcome can be
      attributed to innovations in perioperative methods, image-guided therapy for
      management of postoperative abscesses and other complications and more effective
      antimicrobial therapy. Advances in each area, along with supporting data and the
      limitations of therapy, will be reviewed critically. Methods that have been
      proved by clinical trial will be emphasized.

PMID- 8256187
TI  - A clinical comparison of cefepime and metronidazole versus gentamicin and
      clindamycin in the antibiotic management of surgically treated advanced
      appendicitis.
AB  - Many antibiotics and antibiotic combinations are used for the treatment of
      peritonitis because of advanced (gangrenous or perforated) appendicitis. An
      aminoglycoside combined with an antianaerobe antibiotic is one standard
      treatment, but there is concern about the potential nephrotoxicity of the
      aminoglycoside and the necessity for monitoring aminoglycoside blood levels.
      Cefepime, a new broad-spectrum cephalosporin with a prolonged serum half-life,
      has excellent activity against gram-positive and gram-negative bacteria,
      including Pseudomonas aeruginosa. Its spectrum of activity is similar to the
      aminoglycosides, but it has less potential for inducing renal injury. A double
      blind, randomized study compared cefepime, 2 grams every 12 hours IVPB plus
      metronidazole 0.5 grams every eight hours IVPB (C/M) with gentamicin 1.5
      milligrams per kilograms of IVPB plus clindamycin 0.9 grams q eight hours IVPB
      (G/C), administered up to 14 days, in 96 surgically treated patients with
      gangrenous or perforated appendicitis. Fifty patients had advanced appendicitis
      (nine gangrenous and 41 perforated) in the C/M group and 46 patients (six
      gangrenous and 40 perforated) in the G/C group. The mean number of days of
      postoperative fever (C/M, 4.4 +/- 2.7 versus G/C, 5.0 +/- 2.2), postoperative
      hospitalization (C/M, 2.0 +/- 1.9 versus G/C, 2.0 +/- 2.1) and antibiotic therapy
      (C/M, 6.3 +/- 1.9 versus G/C, 6.9 +/- 1.9) was similar in the two treatment
      groups. There were 11 treatment failures (C/M, three; G/C, eight; p = 0.13), six
      of which were probably a result of enterococci. No deaths occurred. Our study
      results show that the efficacy of cefepime plus metronidazole is equivalent to
      that of clindamycin plus gentamicin.

PMID- 8256188
TI  - A randomized study of cefepime versus the combination of gentamicin and
      mezlocillin as an adjunct to surgical treatment in patients with acute
      cholecystitis.
AB  - In patients with acute cholecystitis, antibiotics are used as an adjunct to
      cholecystectomy to reduce the incidence of postoperative septic complications
      thought to be related to bactibilia. Combinations of penicillins, or
      cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth
      generation cephalosporin with excellent activity against gram-positive and gram
      negative bacteria, including Pseudomonas species. It has a prolonged serum half
      life, allowing twice-daily dosing, and is not nephrotoxic. This study was
      undertaken to determine whether or not cefepime was as effective as the
      combination of gentamicin and mezlocillin in patients with acute cholecystitis.
      One hundred and forty-nine patients were randomized, two to one, to receive
      cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2
      grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight
      hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients
      underwent cholecystectomy. Bile cultures were obtained, and concentrations of
      cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a
      subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable
      gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56
      cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin
      treated patients (29.4 percent). Enterococci were recovered in six cefepime
      treated patients. Clinical and bacteriologic responses were similar for the
      cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure
      in each group, a wound infection in a patient receiving cefepime and a subhepatic
      abscess in a patients receiving gentamicin and mezlocillin. Other measures of
      outcome, such as the number of days of fever, days nothing by mouth, days of
      hospitalization and days of antibiotic therapy were similar in both groups.
      Cefepime, with every 12 hour dosing, achieved extremely high concentrations in
      all tissues assayed at the time of the operation, a mean of eight hours after
      administration. Adverse clinical events were similar in both treatment groups.
      Cefepime is as effective as gentamicin and mezlocillin in preventing septic
      complications after cholecystectomy for acute cholecystitis. Cefepime requires
      fewer doses, does not require drug monitoring, is not associated with
      nephrotoxicity and may therefore prove to be a cost-effective alternative to
      combination therapy that uses an aminoglycoside.

PMID- 8256189
TI  - Cefepime for infections of the biliary tract.
AB  - Antibiotic treatment of biliary tract infections is widely accepted. An open,
      prospective, randomized, multicenter trial comparing cefepime (2 grams every 12
      hours) with gentamicin (1.5 milligrams per kilograms every eight hours) plus
      mezlocillin (3 grams every four hours) for a minimum of five days was undertaken.
      Of the 149 patients enrolled, 120 were evaluable; 80 were randomized to receive
      cefepime and 40 were randomized to receive gentamicin plus mezlocillin (two to
      one randomization schedule). The diagnosis was acute cholecystitis in 101
      patients and acute cholangitis in the remainder. There were no differences
      between the two treatment groups with regard to gender, age, disease, signs and
      symptoms, admitting temperature or laboratory values. All patients (100 percent)
      treated with gentamicin and mezlocillin were cured of the infection, as were 78
      (97.5 percent) of the patients treated with cefepime (difference not
      significant). The incidence and spectrum of adverse events and complications were
      similar between the two groups (8.8 percent for cefepime versus 10 percent for
      gentamicin and mezlocillin). Our data show that the efficacy and safety of
      cefepime administered every 12 hours is equivalent to that of gentamicin and
      mezlocillin combination for treating patients with acute infections of the
      biliary tract. In addition, twice-daily administration of cefepime may be more
      cost-effective than the aminoglycoside-based combination.

PMID- 8256190
TI  - Postoperative pneumonia in the intensive care unit.
AB  - Postoperative pneumonia in the surgical patient may occur from atelectasis and
      inadequate postoperative TV, from ventilator-associated pathophysiology and from
      aspiration. Each process ultimately elicits the proinflammatory responses from
      the lung in the effort to eradicate the infectious pathogens. Postoperative
      pneumonia is best prevented by maintaining a clear understanding of the biologic
      basis for infection in the lung. Therapy requires aggressive tracheobronchial
      drainage strategies and antibiotic therapy directed toward the pathogens that are
      producing the pulmonary inflammatory response.

PMID- 8256191
TI  - Risk of infection, infecting flora and treatment considerations in penetrating
      abdominal trauma.
AB  - Infectious complications postoperatively for penetrating abdominal trauma are a
      major cause of morbidity, which contributes significantly to increased length of
      hospitalization stay and the cost of patient care. The results of recent studies
      have suggested that the probability of a major infection after traumatic
      intestinal perforation of the individual patient can be predicted from risk
      factors noted at the time of the operation. The factor most closely associated
      with the development of infection is peritoneal contamination by intestinal
      contents. Other significant risk factors (p < 0.05) are the number of organs
      injured, number of units of blood administered, ostomy formation for left colonic
      injury and patient age. The risk of patients being infected can be predicted and
      thereby used to guide postoperative treatment decisions. Adjusting trauma care
      choices in antibiotics, duration of antibiotic administration and incisional
      wound management could result in significant savings. Standard operative
      procedures, the use of parenteral antibiotics (the duration of which has been one
      to two days in most recent studies) effective against endogenous aerobic and
      anaerobic organisms and leaving the surgical incision open decrease the incidence
      of postoperative wound infection. Despite such preventive measures, major
      infection remains a problem.

PMID- 8256192
TI  - Emerging problems in gram-positive infections in the postoperative patient.
AB  - Gram-positive bacteria are increasingly prevalent in the postoperative patient
      population and are important as pathogens. As increasingly ill and elderly
      patients undergo surgical treatment and as increased use is made of invasive or
      immunosuppressive treatment modalities, this trend is likely to accelerate. The
      increasing use of broad-spectrum antibiotics results in the emergence of
      resistant pathogens or superinfections that are increasingly difficult to treat.
      Examples of such pathogens include methicillin-resistant Staphylococcus
      epidermidis, vancomycin-resistant enterococci and Clostridium difficile. No acute
      care setting, from large urban teaching hospital to small rural community
      hospital, is immune to the trend. The clinical challenge posed by these organisms
      is compounded by the fact that serious gram-positive infections can be impossible
      to distinguish on clinical grounds from their gram-negative counterparts. The
      host inflammatory response to gram-positive infection is quite similar to that
      caused by gram-negative infection, including elaboration of cytokine mediators
      and progression to visceral organ dysfunction. The clinician must be cognizant
      that serious infections, especially of nosocomial origin, may be caused by gram
      positive bacteria.

PMID- 8256193
TI  - Molecular characteristics of anti-polysaccharide antibodies.

PMID- 8256194
TI  - Content and dynamics of the human antibody variable region repertoire to the
      Haemophilus influenzae type b polysaccharide.

PMID- 8256195
TI  - Natural and pathologic human autoimmune responses to carbohydrate antigens on red
      blood cells.

PMID- 8256196
TI  - Bacterial carbohydrates in neonatal sepsis: targets for immunotherapy.

PMID- 8256197
TI  - Carbohydrate immunity in American trypanosomiasis.

PMID- 8256198
TI  - Antigenic analysis of the saccharide moiety of the lipooligosaccharide of
      Bordetella pertussis.

PMID- 8256199
TI  - Conjugate vaccines: practice and theory.

PMID- 8256201
TI  - In vitro antibody response of human lymphocytes to the Haemophilus influenzae
      type b capsular polysaccharide.

PMID- 8256200
TI  - Anti-idiotypic antibodies as vaccines against carbohydrate antigens.

PMID- 8256202
TI  - Cooperative binding by mouse IgG3 antibodies: implications for functional
      affinity, effector function, and isotype restriction.

PMID- 8256203
TI  - Prospective evaluation of selective venous sampling for parathyroid hormone
      concentration in patients undergoing reoperations for primary
      hyperparathyroidism.
AB  - BACKGROUND: The utility of standard radiologic imaging studies in guiding
      reoperative parathyroid surgery for primary hyperparathyroidism is widely known
      and accepted. The additional information gained by selective venous sampling in
      that patient population has not been well defined. We report the results of our
      experience with this method. METHODS: Between 1982 and 1992, 223 consecutive
      patients underwent reoperations for persistent or recurrent primary
      hyperparathyroidism after a prospectively determined series of imaging studies.
      Patients underwent noninvasive testing consisting of ultrasonography, computed
      tomography, technetium thallium scanning, and magnetic resonance imaging.
      Patients with negative, equivocal, or discordant results on the noninvasive
      studies proceeded to angiography. If angiography was negative, selective venous
      sampling was performed. RESULTS: Eighty-six patients (39%) with negative or
      equivocal noninvasive test and angiogram results underwent selective venous
      sampling. Seventy-six patients (88%) had a significant gradient in levels of
      parathyroid hormone from veins draining the left side of the neck (n = 25), the
      right side of the neck (n = 33), both sides of the neck (n = 7), and the thymus
      (n = 11). Correlation of these findings with operative findings revealed a
      sensitivity of 88% and a specificity of 86%. In the subgroup of patients who
      underwent venous sampling and had completely negative results of standard
      radiologic studies (35 of 86; 40%), 28 patients (80%) had venous gradients and
      seven patients (20%) had no gradient. Of those 28 patients in whom the venous
      sampling gradients were the only positive localization study, the venous
      samplings were helpful in 23 patients (true positive gradients), and the
      operative success rate was 93%. In the seven patients with no positive
      preoperative localizing studies including venous sampling, there were two
      operative failures (operative success, 71%). CONCLUSIONS: Our results show that
      selective venous sampling is a highly sensitive and specific method to regionally
      localize abnormal parathyroid glands not imaged by standard noninvasive and
      invasive radiologic techniques. Venous sampling is the study of choice in guiding
      reoperative procedures for occult abnormal parathyroid glands that are undetected
      despite the use of all available imaging studies.

PMID- 8256204
TI  - Value of technetium 99m sestamibi iodine 123 imaging in reoperative parathyroid
      surgery.
AB  - BACKGROUND: The purpose of this study was to assess the contribution of
      technetium 99m sestamibi iodine 123 (T/S) imaging to preoperative and
      intraoperative management of patients with persistent hyperparathyroidism.
      METHODS: During a period of 10 months, all patients being prepared for
      reoperative parathyroid surgery (n = 10), two patients deemed significant
      operative risks (one patient with severe chronic obstructive pulmonary disease
      and one patient with severe cervical spine ankylosing spondylitis), and two
      patients who had undergone prior thyroid operation were studied with T/S imaging.
      Six patients undergoing reoperative surgery had undergone one, three had
      undergone two, and one had undergone three prior procedures. RESULTS: T/S imaging
      correctly localized 14 of 16 parathyroid tumors. By comparison, only 1 of 6
      thallium technetium and 3 of 12 computed tomography (CT) scans (in seven
      patients) were positive. T/S imaging guided the reoperative surgical approach
      accurately in 12 of 14 patients, including one case of an undescended left lower
      gland at the level of the mandible and identification of a third gland on the
      left in another case. Sternal split was required to remove three lesions
      localized by T/S imaging, two beneath the aortic arch and one nestled in the
      aortopulmonary window in a patient who had undergone two prior procedures
      including a sternal split. In these three cases T/S imaging was particularly
      useful, because CT scans, thallium technetium scans, magnetic resonance imaging,
      and arteriography were not diagnostic. The outcome after operation was favorable
      in all 14 cases, with correction of hypercalcemia and no permanent laryngeal
      nerve injuries or hypocalcemia. CONCLUSIONS: We concluded that T/S imaging is
      more accurate than thallium technetium and CT scans in evaluation of patients
      with persistent hyperparathyroidism.

PMID- 8256205
TI  - Clinical usefulness of an intraoperative "quick parathyroid hormone" assay.
AB  - BACKGROUND: Intraoperative assays of parathyroid hormone (PTH) in the surgical
      management of hyperparathyroidism have been limited by an extended "turnaround"
      time, making it impractical for the operating surgeon. With our modification of a
      standard immunoradiometric assay for intact PTH, results are reported in 12
      minutes. The operative usefulness and the ability of this "quick PTH" assay to
      predict postoperative serum calcium levels are reported here. METHODS: Quick PTH
      levels from whole blood samples taken 10 minutes after excision of
      hyperfunctioning parathyroid glands were compared with preoperative and
      preexcision samples in patients undergoing 63 parathyroidectomies. Patients were
      divided into two groups with assay incubation times of 10 and 6 minutes. The
      latter was clearly not sensitive enough and resulted in a 20% false-negative
      rate. However, with a 10-minute incubation time, a decrease of 54% or more in
      quick PTH levels resulted in postoperative normocalcemia in patients with primary
      hyperparathyroidism. RESULTS: With these criteria used to predict the
      postoperative return to normocalcemia in 29 patients with primary
      hyperparathyroidism, the quick PTH assay had a sensitivity of 96%, specificity of
      100%, and overall accuracy of 97%. CONCLUSIONS: The quick PTH assay was
      especially helpful in predicting postoperative calcium levels when multiple
      excisions were necessary to remove all hyperfunctioning tissue or some normal
      parathyroid glands were not visualized.

PMID- 8256206
TI  - Success of unilateral neck exploration for sporadic primary hyperparathyroidism.
AB  - BACKGROUND: Unilateral neck exploration for primary hyperparathyroidism (PHPTH)
      is controversial because of concern about missed multiglandular disease. METHODS:
      In patients with sporadic PHPTH our approach has been arbitrarily to surgically
      explore the right neck first unless preoperative or intraoperative evidence
      suggests left-sided parathyroid pathologic condition. When an adenoma is
      identified and a normal ipsilateral gland is confirmed on histologic examination,
      the contralateral side is not explored. A 15-year series of 371 patients with
      sporadic PHPTH was reviewed retrospectively to determine the efficacy of this
      strategy. RESULTS: At operation unilateral exploration was possible in 125
      patients (34%). Of these 122 had a single adenoma and two patients had
      parathyroid carcinoma. One patient with unrecognized hyperplasia required
      subsequent subtotal parathyroidectomy. There were no major complications.
      Bilateral surgical exploration was required in 246 patients including 18 with
      hyperplasia, 4 with double adenomas, and 4 with parathyroid cancer. Bilateral
      surgical exploration failed in 18 patients (14 persistent and 4 recurrent PHPTH)
      and was complicated by one recurrent nerve palsy and two cases of permanent
      hypocalcemia. Operative time was significantly shorter in the unilaterally
      explored group. CONCLUSIONS: When possible, unilateral exploration for PHPTH is
      safe and effective, avoids obliterative scarring of the contralateral neck, and
      may reduce morbidity and operative time.

PMID- 8256207
TI  - Surgical and medical management of patients with pulmonary metastasis from
      parathyroid carcinoma.
AB  - BACKGROUND: The aim of this study was to characterize patients with pulmonary
      metastasis of parathyroid carcinoma and to evaluate the long-term effect of
      surgical and medical therapy. METHODS: Seven patients with pulmonary metastasis
      of parathyroid carcinoma were treated between 1980 and 1992. Six patients
      underwent resection of pulmonary metastases, and one patient has had long-term
      bisphosphonate therapy alone. Bisphosphonate was also given before or after
      operation to three patients. RESULTS: Two patients underwent a unilateral
      thoracotomy for a single pulmonary lesion, and four other patients with multiple
      lesions underwent staged bilateral thoracotomies. The postoperative serum calcium
      level returned to normal after each thoracotomy in three patients who were alive
      and well 3, 8, and 12 years after the first thoracotomy. Hypercalcemia persisted
      in the other three patients. In two of the patients, bisphosphonate therapy was
      also unable to control hypercalcemia. In one patient the serum calcium level has
      been maintained in the 13 mg/dl range by bimonthly bisphosphonate therapy alone
      for 3 years. CONCLUSIONS: The aggressive surgical approach to pulmonary
      metastasis of parathyroid carcinoma was shown to be effective for palliation in
      selected patients. Bisphosphonate therapy is an alternative to resection but has
      only a temporary calcium-lowering effect.

PMID- 8256208
TI  - Predicting outcome in papillary thyroid carcinoma: development of a reliable
      prognostic scoring system in a cohort of 1779 patients surgically treated at one
      institution during 1940 through 1989.
AB  - BACKGROUND: Multivariate analyses in papillary thyroid carcinoma (PTC) have shown
      that age, tumor size, local invasion and distant metastasis are independent
      predictive variables. This study attempted to define a reliable prognostic
      scoring system for predicting PTC mortality rates with 15 candidate variables
      that included completeness of primary tumor resection but excluded histologic
      grade and DNA ploidy. METHODS: The study group comprised 1779 patients with PTC
      (followed up for > 26,000 patient-years), divided by treatment dates into 1940 to
      1964 (n = 764) and 1965 to 1989 (n = 1015). Cox model analysis and stepwise
      variable selection led to a prognostic model initially derived from the training
      set (n = 764). The initial prognostic score was thereafter validated externally
      with the later (1965 to 1989) "test" data set. RESULTS: The final model included
      five variables abbreviated by metastasis, age, completeness of resection,
      invasion, and size (MACIS). The final prognostic score was defined as MACIS = 3.1
      (if aged < or = 39 years) or 0.08 x age (if aged > or = 40 years), + 0.3 x tumor
      size (in centimeters), +1 (if incompletely resected), +1 (if locally invasive),
      +3 (if distant metastases present). Twenty-year cause-specific survival rates for
      patients with MACIS less than 6, 6 to 6.99, 7 to 7.99, and 8+ were 99%, 89%, 56%,
      and 24%, respectively (p < 0.0001). CONCLUSIONS: Because the five variables
      needed for MACIS scoring are readily available after primary operation, such a
      prognostic system could have widespread applicability in assessment of PTC.

PMID- 8256209
TI  - Thyroid-stimulating hormone activates phospholipase C in normal and neoplastic
      thyroid tissue.
AB  - BACKGROUND: Thyroid-stimulating hormone (TSH) stimulates thyroid growth through
      two signal transduction pathways: the G protein-adenylate cyclase system and the
      G protein-phospholipase C (PLC) system. The adenylate cyclase system has been
      studied extensively, but there is little information available concerning PLC
      activity in thyroid neoplasms. METHODS: Human thyroid membranes were incubated
      for 30 minutes at 37 degrees C in the presence or absence of bovine TSH (300
      mU/ml). PLC activity was assayed by liberation of inositol phosphates from the
      enzymatic hydrolysis of tritiated phosphatidylinositol bisphosphate. Fifty-six
      tissues were assayed (normal, 23; multinodular goiter, 5; follicular adenoma, 9;
      and differentiated thyroid cancer, 19 [9 low risk and 10 high risk]). RESULTS:
      TSH significantly increased PLC activity in normal, benign, and most malignant
      thyroid neoplasms. Although there were no differences in basal or TSH-stimulated
      PLC activity between the groups of normal thyroid, multinodular goiter,
      follicular adenoma, or the cancers, one half of the high-risk cancers had an
      aberrant PLC response. CONCLUSIONS: This is the first demonstration that TSH
      stimulates PLC activity in normal and neoplastic human thyroid tissue. Aberrant
      TSH-stimulated PLC activity was present in half of the aggressive thyroid
      neoplasms.

PMID- 8256210
TI  - Impact of therapeutic regional lymph node dissection for medullary carcinoma of
      the thyroid gland.
AB  - BACKGROUND: Medullary carcinoma of the thyroid gland (MCT) is a disease commonly
      associated with regional metastases. Apart from surgical resection, there are
      limited therapeutic options for such patients. Given the variable and often
      prolonged survival of such patients, the benefit of surgical resection is
      difficult to evaluate. We have reviewed our experience with regional lymph node
      dissection for metastatic MCT. METHODS: From Jan. 1, 1980, to Dec. 31, 1991, 36
      patients underwent dissection of regional lymph node metastases for MCT at our
      institution. Survival was calculated by the Kaplan-Meier method and comparisons
      by log rank analysis. Significance was defined as p < 0.05. RESULTS: Thirty-six
      patients (13 women), with a mean age of 48 years (range 16 to 78 years),
      underwent operation for clinically palpable or radiologically identified nodal
      disease. Median follow-up was 53 months, with an overall actuarial 5-year
      survival of 65%. Factors significantly associated with a poor outcome included
      the following: age greater than 40 years, mediastinal metastases, incomplete
      excision, extranodal disease, and failure to reduce the thyrocalcitonin level.
      CONCLUSIONS: The resection of metastatic MCT to regional lymph nodes can be
      associated with appreciable survival. Prognostic parameters are identified that
      adversely affect survival.

PMID- 8256211
TI  - Preoperative localization of occult medullary carcinoma of the thyroid gland with
      single-photon emission tomography dimercaptosuccinic acid.
AB  - BACKGROUND: Patients who undergo thyroidectomy for medullary carcinoma of the
      thyroid gland (MTC) often have elevations of postoperative serum calcitonin
      levels, which are indicative of metastatic or residual disease. It has been
      extremely difficult to localize tumor in these patients with standard diagnostic
      studies such as ultrasonography, computed tomography, or magnetic resonance
      imaging scans. Previous studies have suggested that planar technetium 99m (V)
      dimercaptosuccinic acid (DMSA) scintigraphic scans can localize MTC in these
      patients. We have recently increased the sensitivity of planar scintigraphic
      images by using single-photon emission tomography (SPECT). This study was
      performed to compare the sensitivity of planar DMSA scans with that of SPECT DMSA
      scans. METHODS: Two normal volunteers and three patients with occult MTC after
      previous total thyroidectomy underwent planar and SPECT DMSA scans. Each patient
      subsequently underwent surgical exploration based on the DMSA scans. RESULTS:
      Physiologic DMSA uptake was noted in the nasopharynx, axial skeleton, breast,
      liver, spleen, heart, kidneys, urinary bladder, great vessels, and skeletal
      muscles in both normal volunteers and patients with occult MTC. Planar DMSA scans
      and dynamic computed tomographic scans failed to localize MTC in any of these
      patients who had minimal disease. SPECT DMSA scans correctly localized cervical
      MTC in two of three patients, as proved by subsequent surgical resection. One
      patient who had a negative cervical exploration is presumed to have had a false
      positive SPECT DMSA scan. CONCLUSIONS: SPECT DMSA scans appear to be a sensitive,
      safe, and noninvasive localization technique for patients with occult MTC who
      have undergone previous thyroidectomy.

PMID- 8256212
TI  - Reoperation for recurrent or persistent medullary thyroid cancer.
AB  - BACKGROUND: Initial operations for medullary thyroid cancer (MTC) frequently do
      not eradicate all disease, as evidenced by persistently elevated levels of
      stimulated plasma calcitonin. METHODS: Thirty-two patients with MTC and elevated
      stimulated plasma calcitonin levels after thyroidectomy were studied between 1990
      and 1993. Thirty-five repeat neck explorations and microdissections were
      performed. Four patients also underwent a median sternotomy and mediastinal
      dissection. RESULTS: In nine patients (group 1), stimulated plasma calcitonin
      levels were undetectable after reoperation, whereas in 13 cases (group 2) the
      calcitonin levels decreased by 40% or more. In 10 cases (group 3) the CT levels
      did not decrease. Primary tumors that exhibited invasive features (invasion of
      adjacent structures or extranodal or extracapsular spread) were found more often
      in patients from group 3 than in patients from groups 1 or 2 (p < 0.05, Fisher's
      exact test). CONCLUSIONS: Reoperation resulted in normalization of calcitonin
      levels in 28% of patients and a decrease in calcitonin levels by 40% or more in
      another 42% of patients. The data also suggest that patients whose primary MTC
      has invaded tissues beyond the thyroid gland or a lymph node capsule are less
      likely to benefit from repeat operation.

PMID- 8256213
TI  - Prospective, randomized, double-blind study about effectiveness of levothyroxine
      suppressive therapy in prevention of recurrence after operation: result at the
      third year of follow-up.
AB  - BACKGROUND: Levothyroxine has often been given to patients operated on for
      nodular goiter to prevent recurrence. The rationale is that suppression of
      thyroid-stimulating hormone (TSH), considered to be the main growth factor in
      this disease, can be obtained by administration of levothyroxine. METHODS: Sixty
      patients undergoing operation for nontoxic nodular goiter were randomized in two
      groups: (1) thirty-two were administered levothyroxine at substitutive dosage
      (100 micrograms) or placebo and (2) twenty-eight were given levothyroxine at
      suppressive dosage (2.2 to 3 micrograms/kg/day). Levels of thyroid hormones and
      TSH were evaluated every 6 months. Recurrences detected by echography were then
      considered. RESULTS: After a 3-year follow-up we observed 25 of 32 recurrences in
      group 1 and 6 of 28 in group 2 (p < 0.005). Subjects with endemic goiter problems
      responded better to therapy. Patients with a multinodular goiter responded better
      than patients with a uninodular goiter. No difference was found regarding the
      type of surgical treatment (subtotal thyroidectomy vs lobectomy). CONCLUSIONS:
      The results confirmed suppressive therapy as actually being effective in
      preventing recurrences at least in iodine-deficient regions like Italy. Thus for
      these patients it may be suggested as a prophylactic treatment after operation.

PMID- 8256214
TI  - Management of ectopic thyroid nodules.
AB  - BACKGROUND: Surgical dictum states that the so-called lateral aberrant thyroid
      represents metastatic thyroid cancer. METHODS AND RESULTS: We present sixteen
      cases of patients with benign ectopic thyroid tissue. Seven cases were discovered
      during evaluation and treatment of hyperparathyroidism. The remaining nine cases
      were discovered during the evaluation and treatment of thyroid disorders or
      cervical nodules. In fifteen cases there is benign histology on the nodules. One
      case has been followed for 4 years with scans revealing a normal thyroid gland
      with an unchanging ectopic thyroid nodule in the superior mediastinum. In eight
      of our cases there have been thyroid resections searching for occult carcinomas.
      Histologic examination on these eight thyroid glands revealed either normal
      thyroid or benign nodules. CONCLUSIONS: Not all lateral aberrant thyroid tissue
      is malignant. The histologic condition of the nodule combined with intraoperative
      examination of the ipsilateral thyroid lobe can reliably guide therapy. The old
      dictum concerning lateral aberrant thyroid representing metastatic cancer should
      be removed from or modified in review texts and surgical examinations.

PMID- 8256215
TI  - Surgery still has a role in Graves' hyperthyroidism.
AB  - BACKGROUND: A recent survey of American thyroidologists defining their management
      of a 43-year-old woman with hyperthyroid Graves' disease and a thyroid weighing
      40 to 50 grams revealed that 69% recommended iodine 131 therapy, 30% prolonged
      antithyroid drug therapy, and only 1% operation. If the patient was younger or
      had a larger thyroid, 4% to 7% of the respondents recommended operation. METHODS:
      In our clinic we often recommend operation for young adult patients with large
      goiters who have had recurrent hyperthyroidism after antithyroid drug (ATD)
      therapy, have allergic reactions to ATD, are not compliant, are ATD failures, or
      refuse 131I therapy. Thus operation for Graves' disease is recommended more
      frequently in our clinic than this survey indicates. From 1980 to 1992, 81
      patients with Graves' disease (15 men and 66 women; mean age, 30 years) underwent
      a subtotal thyroidectomy. Patients had been pretreated with antithyroid drugs and
      saturated solution of potassium iodide, and thyroid conditions were normal at the
      time of operation. All patients underwent subtotal thyroidectomy by one surgeon
      and 3 to 5 grams of thyroid were left on each side. RESULTS: There was no
      permanent recurrent nerve damage or hypoparathyroidism. Hyperthyroidism recurred
      in one patient (1.2%). Hypothyroidism developed in 59% of our patients, 77%
      within 1 year after operation, which was easily managed with replacement doses of
      levothyroxine. Ophthalmopathy had not developed or progressed in any patient, as
      has recently been suggested to occur after 131I therapy of Graves' disease.
      CONCLUSIONS: Because our patients are almost always hospitalized for no more than
      24 to 36 hours, have had no complications except for hypothyroidism, have had
      their disease abruptly terminated, did not have ophthalmopathy, required far
      fewer physician visits and laboratory tests compared with patients treated with
      ATD or 131I, surgery remains a reasonable approach to the management of Graves'
      disease.

PMID- 8256216
TI  - Amiodarone-induced thyrotoxicosis: clinical presentation and expanded indications
      for thyroidectomy.
AB  - BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) is a rare disorder that is
      frequently refractory to conventional pharmacologic therapy. METHODS: An analysis
      of seven patients who underwent thyroidectomy for control of AIT between 1987 and
      1993 was completed to examine the clinical manifestations and the indications for
      surgical therapy. RESULTS: Five men and two women, 53 to 72 years of age, had AIT
      after 3 to 55 months of amiodarone treatment (mean, 21 months). The primary
      manifestations of AIT were ventricular tachycardia (five), exacerbation of
      chronic pulmonary disease (one), and occult hyperthyroidism (one). Medical
      therapy included propylthiouracil in doses up to 1200 mg/day in five patients, a
      beta-receptor antagonist in three, and withdrawal of amiodarone in five. Near
      total or total thyroidectomy resulted in resolution of thyrotoxicosis in all
      patients. Morbidity included pneumonia (one) and cardiac dysrhythmias (two). One
      patient died of ventricular dysrhythmias 4 months after thyroidectomy. The mean
      thyroid weight was 50 gm (range, 17 to 216 gm). Microscopic examination showed
      destructive follicular lesions with fibrosis in all patients. Associated thyroid
      pathologic condition included multinodular goiter in four patients and a
      follicular adenoma in one. CONCLUSIONS: AIT may be clinically occult or
      manifested by unusual symptoms requiring a high index of suspicion for diagnosis.
      Near-total thyroidectomy is safe and effective in producing rapid resolution of
      AIT and is indicated for the initial treatment of patients who present with a
      resurgence of life-threatening cardiac arrhythmias and for all patients with AIT
      refractory to medical therapy.

PMID- 8256217
TI  - Early experience with laparoscopic approach for adrenalectomy.
AB  - BACKGROUND: Adrenalectomy performed by a posterior or transabdominal approach
      causes substantial postoperative pain. The purpose of this study was to evaluate
      laparoscopy as a potential approach for adrenalectomy. METHODS: We performed 25
      consecutive laparoscopic adrenalectomies on 22 patients from April 1, 1992, to
      March 30, 1993. Laparoscopic surgery was performed by using a lateral decubitus
      flank approach with four 11 mm trocars. RESULTS: Twelve right and 13 left adrenal
      glands were removed in a mean time of 2.3 hours. Three patients underwent
      bilateral adrenalectomies in a mean time of 5.3 hours. The 15 women and 7 men
      range in age from 31 to 60 years (mean, 42 years). The adrenal gland diseases
      were nonfunctional adenoma (seven), pheochromocytoma (five), Cushing's disease
      (four), Cushing's adenoma (four), primary aldosteronism (two),
      dehydroepiandrostenedione sulfate hypersecretion (one), angiomyolipoma (one), and
      medullary cyst (one). Average tumor size was 4.1 cm (range, 1 to 15 cm).
      Laparoscopic adrenalectomy was successful in 96% of patients, with one patient
      requiring a laparotomy because of inadequate exposure. The median postoperative
      stay was 4 days (range, 2 to 19), with a mean of five narcotic injections. There
      were no deaths, and morbidity was minor. CONCLUSIONS: Laparoscopy can be used
      successfully for adrenalectomy. It produces less postoperative pain and rapid
      return to normal activity. It may be the preferred method for removing most
      adrenal gland lesions that require operation.

PMID- 8256218
TI  - Safety of the posterior approach in adrenal surgery: experience in 105 cases.
AB  - BACKGROUND: At the advent of laparoscopic adrenalectomy when it was timely to
      reappreciate the results of time-honored procedures, we reviewed the cases of 105
      patients who underwent adrenalectomy through the posterior approach. METHODS:
      Between 1970 and 1992 among 331 patients, 105 underwent adrenalectomy through the
      posterior approach (0 of 111 pheochromocytomas, 48 of 64 Conn's disease, 37 of 57
      Cushing's disease, 2 of 20 virilizing-feminizing tumors, 13 of 61 nonsecreting
      adrenalomas, 3 of 12 metastases, 2 of 6 cysts). Adrenalectomy was bilateral in 20
      cases. Among 86 tumors, 28 (32.6%) were larger than 5 cm in diameter, none
      exceeding 10 cm. Posterior approach, initially performed in the prone position,
      was used in the lateral position for the last 40 patients with tumors. A hockey
      stick incision was made on the twelfth or eleventh rib, which was resected.
      RESULTS: During operation no patient died; one minimal caval tear and 13 pleural
      tears occurred and were sutured, with two pleural drainages; six patients
      received blood transfusion. Average operative time was 132 minutes (range, 45 to
      290 minutes). After operation one patient died of iatrogenic sepsis, average time
      to ambulation was 1.5 days, and average in-hospital stay was 7.6 days (range, 1
      to 21), which after the fourth day was mostly justified for nonsurgical reasons.
      From 1990 through 1992, 37 of 38 patients were walking the day after operation
      and average postoperative stay dropped to 4.5 days (range, 1 to 7 days).
      CONCLUSIONS: Adrenalectomy through the posterior approach is safe and allows
      early postoperative discharge.

PMID- 8256219
TI  - Fine-needle aspiration biopsy of adrenal masses in patients with extraadrenal
      malignancy.
AB  - BACKGROUND: Reports evaluating the efficacy of fine needle aspiration (FNA) of
      the adrenal gland have suggested a possible correlation between size of an
      adrenal mass and the presence of a primary or metastatic malignancy. These
      studies have focused on FNAs of all adrenal gland masses regardless of clinical
      history. This study investigates this relationship in a subpopulation of patients
      with a known history of primary extraadrenal malignancy. METHODS: All patients
      who have undergone computed tomographic-guided FNA biopsy of an adrenal mass at
      Loyola University Medical Center and Hines Veterans Administration Hospital, from
      1985 to 1991, were reviewed. RESULTS: If size was assumed to be an independent
      predictor for presence of metastases, the highest efficiency was obtained with a
      cutoff value of 3 cm. This value divided the group into 15 (42%) "low-risk" (< or
      = 3 cm) and 21 (58%) "high-risk" (> 3 cm) subjects. In the "low-risk" group, 87%
      of the masses (13 of 15) were benign and 13% (2 of 15) were malignant. Within the
      "high-risk" group, more than 95% of the masses (20 of 21) were malignant, with a
      single (5%) benign case (p < 0.05). CONCLUSIONS: There is a significant
      correlation between the size of an adrenal nodule and the presence of metastases
      in patients with a known primary extraadrenal malignancy. Nodules greater than 3
      cm have a very high probability of involvement by metastatic tumor. Nodules 3 cm
      or smaller are usually benign, but metastatic tumor can still be found in up to
      13%. FNA biopsy is useful in evaluating adrenal masses in this setting.

PMID- 8256220
TI  - Effective reversibility of the signs and symptoms of hypercortisolism by
      bilateral adrenalectomy.
AB  - BACKGROUND: The long-term outcome of bilateral adrenalectomy in the management of
      patients with Cushing's syndrome has not been previously well studied. METHODS:
      We reviewed our long-term results in 34 patients treated with bilateral
      adrenalectomy between 1983 and the present. Fourteen presented with occult or
      metastatic ectopic adrenocorticotropic hormone (ACTH) syndrome, 10 with failed
      treatment of Cushing's disease, five with primary micronodular and four with
      massive macronodular adrenocortical disease and one with indeterminate cause of
      Cushing's syndrome. RESULTS: All patients underwent bilateral adrenalectomy. Of
      19 patients who required antihypertensive medications before operation, 15 (79%)
      had significant improvement and were either off all antihypertensive medication
      or required less medication after operation. Of 7 patients who required
      medications for diabetes mellitus, after operation 6 (86%) required no medication
      or changed from injections to oral hypoglycemic agents. Of 9 patients with mood
      changes or depression, the symptoms of 8 (88%) resolved. Of 29 patients with
      documented weight gain, 23 (79%) showed marked weight loss. Of 13 hirsute
      patients, 10 (77%) had resolutions of symptoms. Of 21 patients with complaints of
      fatigue, the symptoms of 16 (76%) resolved. Of 8 women with amenorrhea, 6 (75%)
      had resolution of symptoms. Each patient in the primary adrenocortical disease
      group, except one with residual fatigue, had complete resolution of his or her
      symptoms. There was no difference in resolution of symptoms between the ectopic
      ACTH and Cushing's disease groups. Six patients died: in the ectopic ACTH group
      one died of suicide at 1 month, and four of metastatic tumor at 9, 24, 25, and 48
      months, and the patient with macronodular adrenocortical hyperplasia died of a
      myocardial infarction at 30 months. The remainder of the patients have been
      followed for a mean of 32 months (3 to 67 months). None of the patients had any
      evidence of recurrent hypercortisolism. CONCLUSIONS: We conclude that bilateral
      adrenalectomy is a safe, effective, and long-lasting method to ameliorate the
      devastating signs and symptoms of hypercortisolism in patients with Cushing's
      syndrome.

PMID- 8256221
TI  - Clinical features of duodenal somatostatinomas.
AB  - BACKGROUND: Duodenal somatostatinomas are rare tumors that are often asymptomatic
      or present with local symptoms rather than with evidence of excess somatostatin
      production. To characterize the clinical presentation and management of these
      neoplasms we reviewed the course of four patients. METHODS: The records of three
      men and one woman with duodenal somatostatinomas, who were treated between 1988
      and 1992, are reviewed. RESULTS: Three of the patients presented with vague
      gastrointestinal complaints, and one was free of symptoms. No patient had
      symptoms of somatostatinoma syndrome, nor did any have associated
      neurofibromatosis. Three patients were diagnosed after biopsy of a submucosal
      mass during upper endoscopy. Three patients with tumors that measured less than 2
      x 2 cm underwent local resection. One patient with a large tumor and liver
      metastases underwent a Whipple's operation and resection of the liver lesions.
      Immunohistochemically all tumors predominantly contained somatostatin, although
      each had traces of other neuropeptides. All tumors contained psammoma bodies.
      Follow-up periods ranged from 1 to 4 years. CONCLUSIONS: Duodenal
      somatostatinomas often appear with only local symptoms or are completely
      asymptomatic. Small tumors may be locally excised. Intraarterial methylene blue
      injection may help localize very small tumors during operation. Larger tumors,
      including those with localized metastases, should also be resected when possible.

PMID- 8256223
TI  - Comparison of adrenal and extraadrenal pheochromocytomas.
AB  - BACKGROUND: It is commonly believed that extraadrenal tumors (EAT) of the
      paraganglion system are more likely to be malignant than adrenal tumors (AT) and
      carry a poorer prognosis. We analyzed 73 paraganglion tumors (PT) to determine
      whether EATs are more likely to be malignant or have a poorer prognosis than ATs.
      METHODS: A review of patients with PTs at three institutions was performed.
      Malignant tumors were defined as those that metastasized. Comparison of the
      frequencies of malignant tumors was performed by chi-squared analysis. Survival
      distributions were determined by Kaplan and Meier analysis. Comparison of
      survival distributions was performed by log-rank analysis. RESULTS: There were 73
      patients. There were 51 ATs, of which 24 were malignant, and 22 EATs, of which 11
      were malignant (p = 0.82). The 5-year survival rate was 77% for patients with ATs
      and 82% for patients with EATs (p = 0.29). The 5-year survival rate for patients
      with malignant ATs was 57%, and 74% for patients with malignant EATs (p = 0.15).
      There were no significant differences in disease-free survival rates on the basis
      of tumor site. CONCLUSIONS: We were unable to demonstrate that EATs are
      significantly more likely to be malignant than ATs. The survival and disease-free
      survival rates for malignant ATs and EATs are similar, and among malignant
      tumors, there may be no prognostic value of the anatomic location.

PMID- 8256222
TI  - Pheochromocytoma--continuing evolution of surgical therapy.
AB  - BACKGROUND: The management of pheochromocytoma has evolved through refinements in
      diagnosis, localization, and pharmacologic therapy for hemodynamic control both
      before and during operation. To provide a benchmark for comparison and to assess
      the feasibility of surgical resection using a posterior or laparoscopic approach,
      we reviewed the overall management and outcome of 110 patients who underwent
      primary resection of pheochromocytoma or paraganglioma between 1980 and January
      1992 at the Mayo Clinic. METHODS: Patient records were reviewed for demographic
      information, associated conditions, symptoms, laboratory evaluation, localizing
      techniques, preoperative adrenergic blockade, intraoperative hemodynamics, tumor
      location, pathologic conditions, and outcome. RESULTS: The most prominent
      symptoms included headaches, sweating, and palpitations. Forty-seven percent of
      patients had sustained hypertension, and classic paroxysmal attacks were present
      in 72%. The combination of urinary metanephrines and vanillylmandelic acid had a
      sensitivity of 98% in detecting the disease. The positive and negative predictive
      values for localization of tumors by computed tomography scan were 95% and 100%,
      respectively. With routine alpha- and beta-blockade, there were no complications
      associated with intraoperative hypertension. Perioperative mortality was less
      than 1% and morbidity was 16%. More than 90% of patients were restored to a
      condition of normotension; only 20% of these required medication. CONCLUSIONS:
      Surgical resection of these tumors, via a transabdominal approach, can be
      accomplished safely and hospitalization usually extends a week. Today the
      diagnosis, localization, preoperative blockade, intraoperative hemodynamic
      control, and postoperative management have reached a level sufficient to permit
      either a posterior or laparoscopic approach, but only if they can be mastered
      technically.

PMID- 8256224
TI  - Medicolegal analysis of errors in diagnosis and treatment of surgical endocrine
      disease.
AB  - BACKGROUND: The medicolegal impact of adverse events in surgical endocrine
      disease has not been described previously. This study was undertaken to determine
      the causes, costs, and outcomes of endocrine malpractice litigation. METHODS:
      Jury verdict reports from the U.S. civil court system from 1985 through 1991 were
      reviewed. Sixty-two malpractice cases were identified from 21 states. RESULTS:
      The 62 cases were classified into three categories, totaling 63 adverse events:
      (1) complications (n = 34, 54%) from thyroid (n = 32, 51%) or parathyroid (n = 2,
      3%) surgery; (2) delayed diagnosis (n = 22, 35%) of thyroid cancer (n = 11, 18%),
      adrenal tumors (n = 9, 14%), and hyperparathyroidism (n = 2, 3%); and (3) medical
      morbidity (n = 7, 11%) from radioactive iodine (n = 5, 8%) or from
      propylthiouracil (n = 2, 3%). Surgical injuries, mostly recurrent nerve injuries
      by general surgeons, accounted for the greatest number of cases and the highest
      cost of litigation. CONCLUSIONS: Medical malpractice involving endocrine disease
      results in expensive litigation, a result of serious harm. Technical
      misadventures account for most cases, followed closely by delays in diagnosis.
      These data may aid design of risk prevention strategies in endocrine disease.

PMID- 8256225
TI  - Persistent hypertension after successful adrenal operation.
AB  - BACKGROUND: Up to 80% of patients with adrenocortical tumors comprising Conn's or
      Cushing's syndrome and patients with pheochromocytomas suffer from hypertension.
      Its implications in cardiovascular disease and its impact on quality of life make
      it the most important aim in therapeutic efforts. The aim of our study was to
      assess the long-term results in postoperative blood pressure after adrenalectomy
      and to evaluate potential risk factors for persistent hypertension. METHODS:
      Forty four patients with adrenal hypertension operated on between April 1986 and
      April 1991 underwent follow-up consisting of exact history, hormonal analysis,
      and adrenal imaging. RESULTS: Forty three patients were reexamined, which showed
      11 patients (26%) with hypertension at dismissal from hospital and 17 patients
      (40%) with hypertension after a median of 2 years. Except for two recurrent
      tumors in adrenocortical carcinoma all patients were surgically cured.
      Antihypertensive medication could be reduced in 13 of 17 patients with persistent
      hypertension. Persistent hypertension did not correlate with the degree of
      preoperative blood pressure elevation, age, and gender, but it did correlate
      strongly with history of hypertension. Patients with normal blood pressure level
      after operation had a mean history of 5.7 years versus 11.5 years in patients
      with persistent hypertension (p < 0.03). CONCLUSIONS: The success of surgical
      treatment for adrenal hypertension strongly depends on early diagnosis and
      surgical intervention.

PMID- 8256226
TI  - Reoperative insulinomas, 1927 to 1992: an institutional experience.
AB  - BACKGROUND: Between 1927 and 1992, 313 patients have undergone surgery for
      insulinoma(s) at our institution, 12% of which were reoperations. We
      retrospectively reviewed all cases (n = 39) of reoperative surgery for persistent
      hyperinsulinism to identify changing patterns in surgical approach, morbidity,
      and outcome and to evaluate the influence of preoperative and intraoperative
      localization studies. METHODS: The diagnosis of endogenous hyperinsulinism has
      evolved from satisfying Whipple's triad to documenting concomitant hypoglycemia
      and endogenous hyperinsulinemia. Thirty-nine patients were divided into two
      groups for comparison: those treated before localization studies were available
      (1927 to 1967) (n = 17) and those treated since that time (n = 22). Initial
      operations were also compared with reoperations among these 39 patients. RESULTS:
      There were 26 women and 13 men (mean age, 42 years). There was at least one
      positive preoperative localization study in 16 of 22 patients (73%).
      Intraoperative ultrasonogram and careful palpation successfully identified 10 of
      11 tumors in the reoperative setting. Blind or completion pancreatectomies were
      common before 1967 (10 of 17 patients). Since 1967, 14 of 22 patients have
      undergone enucleation of their primary tumor. Operative morbidity increased from
      21% to 58% with reoperation but decreased from 65% to 29% (p = 0.026) when
      comparing the preangiography to the postangiography eras. The development of
      iatrogenic diabetes mellitus occurred in 13 patients (33%) after reoperation.
      Forty-one percent had diabetes before 1967 and 27% since that time (p = not
      significant). Thirty-four of 36 patients (94%) without malignant tumors were
      cured by reoperation. There was one operative death. Survival for patients who
      underwent completion or total pancreatectomy was significantly reduced (p =
      0.003). CONCLUSIONS: Reoperations for persistent hyperinsulinism can be highly
      successful in experienced hands. These reoperations, however, are associated with
      increased morbidity and iatrogenic diabetes. With experience and the use of
      selected localization studies, first-time failures can be avoided in most cases
      thus reducing the need for reoperations and its inherent sequelae.

PMID- 8256227
TI  - The role of surgical endocrinologists in the national cancer program of the
      United States.

PMID- 8256228
TI  - Adult cystic fibrosis: association of acute pulmonary exacerbations and
      increasing severity of lung disease with auxotrophic mutants of Pseudomonas
      aeruginosa.
AB  - BACKGROUND: Pseudomonas aeruginosa has been located in the endobronchiolar spaces
      of patients with cystic fibrosis where nutrients may be limited. In these sites
      it is thought that adaptation of the pathogen might occur and growth factors,
      present in relative excess, may thus promote survival of the organism. Auxotrophy
      of pulmonary isolates of P aeruginosa has previously been shown to be a feature
      of cystic fibrosis and chronic lung sepsis; auxotrophic isolates have additional
      nutritional requirements to the prototrophic "wild types" of the species. A study
      was therefore carried out to determine whether the proportion of auxotrophs
      differs between stable and acutely ill patients, or correlates with the extent of
      underlying disease. METHODS: Sputum samples were cultured for P aeruginosa and
      tested for auxotrophy by spreading serial dilutions of homogenised sputum on to a
      minimal medium which supports only prototrophs, and a complete medium which
      supports both nutritional types. The proportion of auxotrophs to prototrophs was
      determined and growth factors of confirmed auxotrophs were identified. RESULTS:
      Thirty two (86%) of 37 adults with cystic fibrosis infected with P aeruginosa
      harboured auxotrophs; methionine dependent mutants were isolated from seven of 16
      patients tested (44%). More than 50% of the total number of colonies were
      auxotrophic in 19 of 26 samples (73%) from patients with acute exacerbations and
      in only six of 15 samples (40%) from clinically stable patients. In four patients
      from whom samples in both the acute and stable states were available, the
      proportion of auxotrophs fell in the sample taken when stable. Auxotrophs
      predominated in all samples from 11 of those patients with very severe underlying
      lung disease, in contrast to 13 of 30 samples from patients with less severe
      disease. There was no association between the percentage of auxotrophs and the
      presence of other respiratory pathogens. CONCLUSIONS: The majority of adults with
      cystic fibrosis infected with P aeruginosa harbour auxotrophs in the sputum. A
      significant proportion of acutely ill patients and those with severe underlying
      disease have a preponderance of auxotrophs in the sputum compared with stable
      patients and those with less severe disease.

PMID- 8256229
TI  - In vitro bioelectric properties of bronchial epithelium from transplanted lungs
      in recipients with cystic fibrosis.
AB  - BACKGROUND--Bronchial epithelial function after heart-lung transplantation (HLT)
      for cystic fibrosis (CF) may be affected by the original disease as well as other
      factors such as prolonged organ ischaemic time, the interruption of bronchial
      arterial and lymphatic supply, infection, rejection, and cyclosporin. In vitro
      measurement of the bioelectric properties of the bronchial mucosal lining may be
      an effective means of characterising the mucosal function of the lung allografts
      in response to pharmacological agents. METHODS--Bronchial mucosal tissues from
      explanted native lungs of CF and non-CF patients at transplantation were used to
      assess the possible application of a mini-Ussing chamber. With this technique,
      the bioelectric responses of bronchial mucosal biopsies from six patients with
      CF, one patient with congenital heart disease, four with primary pulmonary
      hypertension, and one with emphysema, all after HLT, were studied. The
      bioelectric and pharmacological responses of biopsies of bronchial mucosa from
      patients after HLT were compared with biopsies from non-CF non-HLT subjects.
      RESULTS--The altered bioelectric properties of CF tissues could be detected by
      the mini-Ussing chamber technique. The basal bioelectric values and the responses
      to amiloride and isoprenaline in CF patients were not different from those in non
      CF patients two years after HLT. No significant difference in the basal
      bioelectric properties and responses to amiloride and isoprenaline was found
      between HLT recipients and non-CF non-HLT subjects. CONCLUSIONS--The mini-Ussing
      chamber is an effective means of characterising the typical CF bioelectric defect
      which was not found in the transplanted lungs of CF patients up to two years
      after HLT. Furthermore, values were unaltered in comparison with non-transplanted
      lungs, suggesting that bronchial epithelial function is maintained after HLT.

PMID- 8256230
TI  - Relation between distal airspace size, bronchiolar attachments, and lung
      function.
AB  - BACKGROUND--Smoking related fixed airway obstruction may be due to airway
      scarring and narrowing or decreased support due to loss of adjacent alveolar
      walls. In this study of resected specimens, preoperative pulmonary function was
      compared with results of a morphometric study of lung structure. METHODS-
      Morphometric measurements were made on 42 inflation fixed lung specimens as
      follows: airspace wall surface area per unit volume (AWUV) was measured on at
      least 25 l mm2 histological fields from each specimen, expressed as a mean, and
      the mean of the lowest five measurements for each case (LF5). Minimum diameter,
      maximum diameter, diameter ratio (ellipticality), lumen area, and lumen
      circumference were measured on at least 16 non-respiratory bronchioles from each
      lung. Peribronchiolar alveolar support was measured as mean interalveolar
      attachment distance (IAAD). Measurements of pulmonary function included forced
      expiratory volume in one second (FEV1) (absolute and % predicted values; n = 42),
      slope of phase III (single breath nitrogen test; n = 28), closing volume
      (expressed as a percentage of vital capacity (CV/VC%); n = 28). RESULTS-
      Bronchiolar size was not independently related to the tests of lung function
      used. Percentage predicted FEV1 was related to mean IAAD, ellipticality, and mean
      AWUV. CV/VC% showed significant relation with ellipticality, mean AWUV, and LF5
      AWUV. Slope of phase III increased with increasing IAAD. Significant correlations
      were found between ellipticality and AWUV (mean and LF5), and between
      ellipticality and IAAD. Both IAAD and ellipticality were significantly increased
      in patients with abnormally low FEV1. CONCLUSION--Destruction of airspace walls,
      particularly those attached to the peripheral bronchioles, is more influential in
      determining airflow limitation than bronchiolar size.

PMID- 8256231
TI  - Variability in ciliary beat frequency in normal subjects and in patients with
      bronchiectasis.
AB  - BACKGROUND: There is a wide variation in tracheobronchial clearance of inhaled
      aerosol in normal subjects and in patients with bronchiectasis, but little
      information is available on the variability in ciliary beat frequency (CBF).
      METHODS: The variability in CBF was measured in 10 nasal mucosal samples from
      each of 19 normal controls and 23 stable bronchiectatic subjects. RESULTS: The
      CBF varied at different mucosal sites in both normal subjects and bronchiectatic
      patients. Although the CBF of the fastest beating cilia was similar in both
      groups, the CBF of the slowest beating cilia was, on average, lower and showed
      greater within subject variation in bronchiectatic than in normal subjects.
      CONCLUSIONS: There is a wide variation in CBF in nasal mucosal samples and this
      is significantly wider in bronchiectatic subjects with some cilia beating slowly.
      This may be a consequence of chronic inflammation or infection.

PMID- 8256232
TI  - Lower respiratory tract symptoms in Queensland schoolchildren: risk factors for
      wheeze, cough and diminished ventilatory function.
AB  - BACKGROUND: The occurrence of respiratory symptoms and abnormal lung function in
      children is known to be influenced by genetic and many environmental factors. The
      association between specific respiratory symptoms in children of school age and
      their parents has been examined. METHODS: Respiratory symptoms and ventilatory
      function were recorded for 4549 schoolchildren in Queensland, Australia. RESULTS:
      The cumulative prevalence of wheezing was 23.1% of 8 year olds and 20.8% of 12
      year olds, and the prevalence of wheezing within the previous 12 months was 13.9%
      and 10.5% respectively. A parental history of asthma or wheeze and hayfever was
      associated with wheeze in the child, but did not affect either the age of onset
      or frequency of episodes. A history of frequent cough in children who had never
      wheezed was associated with a parental history of frequent bronchitis, but less
      strongly with parental wheeze. These familial aggregations were not mediated by
      common exposure to cigarette smoke. Both a history of parental wheeze and
      maternal cigarette use were associated with a decrease in FEF25-75 in the child
      and these effects were additive. CONCLUSIONS: The association of specific
      symptoms (wheeze and cough without wheeze) in parent and offspring is interpreted
      as evidence for different mechanisms of familial transmission, which may be
      genetic.

PMID- 8256234
TI  - Massive haemoptysis caused by congenital absence of a segment of inferior vena
      cava.
AB  - A patient with congenital absence of a part of the inferior vena cava is
      described. This resulted in spontaneous rupture of a bronchial vein leading to
      massive haemoptysis.

PMID- 8256233
TI  - Pulmonary rehabilitation in chronic respiratory insufficiency. 3. Ventilatory
      muscle training.

PMID- 8256235
TI  - Comparison of nebulised aerosol deposition in the lungs of healthy adults
      following oral and nasal inhalation.
AB  - A standard jet nebuliser was used to generate a radiolabelled aerosol and the
      pattern of deposition within the airways of eight healthy adults was studied with
      a gamma camera. Penetration of aerosol to the lung was greatly reduced when
      breathing through the nose compared with mouth breathing.

PMID- 8256236
TI  - Case of spontaneous haemothorax associated with an endodermal sinus tumour.
AB  - Spontaneous haemothorax is rare in infants. A case is reported of a nine month
      old infant who was found to have an endodermal sinus tumour.

PMID- 8256237
TI  - Catamenial haemoptysis: a rare cause.
AB  - Since the first report of pulmonary endometriosis as a cause of catamenial
      haemoptysis all cases have been assumed to be due to pulmonary endometriosis,
      even in the absence of histopathological proof. A case is presented where the
      histological findings were of a pulmonary arteriovenous malformation.

PMID- 8256238
TI  - Guidelines on the management of asthma.

PMID- 8256239
TI  - TGF-beta antibodies: a novel treatment for pulmonary fibrosis?

PMID- 8256240
TI  - Systemic effects of inhaled corticosteroids.

PMID- 8256241
TI  - Drug resistant tuberculosis: problems on the horizon.

PMID- 8256242
TI  - Systemic effects of high dose inhaled steroids: comparison of beclomethasone
      dipropionate and budesonide in healthy subjects.
AB  - BACKGROUND: Systemic absorption of inhaled corticosteroids may adversely
      influence the function of the hypothalamo-pituitary-adrenal axis, bone
      metabolism, and circulating leucocytes. These changes can be used to assess the
      safety of different types and modes of administration of these drugs. METHODS:
      The study was a randomised, double dummy, crossover design with nine healthy
      adults. It compared the effects of beclomethasone dipropionate and budesonide
      (given by metered dose aerosols with and without their respective large volume
      spacers (Volumatic and Nebuhaler) attached) on serum cortisol, 24 hour urinary
      free cortisol, and plasma osteocalcin concentrations, and circulating neutrophils
      and lymphocytes. Subjects inhaled the drug (1 mg) and matching placebo at 0900
      and 2200 hours on each of six study days. Blood samples were taken hourly for six
      hours after the morning dose and at the end of the study period. RESULTS: All
      results were within the reference ranges. Both drugs caused similar reductions in
      serum cortisol four to six hours after inhalation. These changes were not
      affected by the use of a large spacer and did not persist at 24 hours. Use of
      spacers tended to increase the haematological effects of the steroids.
      Beclomethasone dipropionate inhaled through a Volumatic provoked a rise in
      circulating neutrophils compared with placebo although lymphocyte numbers were
      unaffected. Budesonide did not influence neutrophil numbers but did reduce
      circulating lymphocytes, numbers of which were further reduced when the Nebuhaler
      was used. There were no significant changes in plasma osteocalcin concentration
      or 24 hour urinary free cortisol excretion with budesonide, with or without a
      spacer. Beclomethasone dipropionate inhaled without a spacer reduced urinary
      cortisol and plasma osteocalcin at 24 hours; however, use of the Volumatic
      protected against these effects. CONCLUSIONS: Attaching a Volumatic reduces the
      systemic effects of 2 mg aerosol beclomethasone dipropionate on the hypothalamo
      pituitary-adrenal axis and circulating osteocalcin concentrations. This study did
      not establish whether the Nebuhaler reduces the systemic effects of budesonide.
      When large spacers are used, 2 mg per day of beclomethasone dipropionate and
      budesonide seem to be equivalent in terms of unwanted effects.

PMID- 8256243
TI  - Effect of eight months of inhaled beclomethasone dipropionate and budesonide on
      carbohydrate metabolism in adults with asthma.
AB  - BACKGROUND: The safety of high dose inhaled steroids has been a subject of
      debate. The efficacy and safety of beclomethasone dipropionate and budesonide
      inhalations were evaluated by measuring their effects on pulmonary function, on
      the hypothalamic-pituitary-adrenocortical axis, and on carbohydrate metabolism in
      adults with unstable asthma. METHODS: Fifteen adults with unstable asthma and 15
      healthy controls were studied. Eight patients were treated with beclomethasone
      dipropionate in initially high (2 mg/day for five months) and subsequently lower
      (1 mg/day for three months) doses. Seven patients were treated with budesonide at
      doses of 1.6 mg/day for five months followed by 0.8 mg/day for three months.
      Blood glucose and serum insulin were measured in an oral glucose tolerance test
      and plasma cortisol in an adrenocorticotrophic hormone test. The antiasthmatic
      effect of treatment was evaluated by measuring peak morning expiratory flow rates
      and forced expiratory volume in one second (FEV1). RESULTS: The FEV1 increased
      significantly after one month of treatment (medians 88% v 96%, p < 0.01), and
      nocturnal symptoms disappeared within two weeks of treatment in both groups. At
      one month, the high dose significantly decreased serum insulin concentrations as
      calculated from the areas under the incremental two hours curves in the glucose
      tolerance test. The decrease was 59% for beclomethasone dipropionate (medians 76
      v 31 mU/l/h, p < 0.005) and 42% for budesonide (medians 79 v 46 mU/l/h, p <
      0.01). The median areas at five and eight months were intermediate for both
      drugs. No significant differences were found when the five and eight month values
      were compared either with the baseline or with one month values. The difference
      between the baseline values of both groups and the respective values in healthy
      controls was significant (medians 79 v 49 mU/l/h, p < 0.01). The one month values
      for the patients and control subjects were similar. Paralleling the changes for
      insulin, the area under the incremental two hour blood glucose curve decreased
      significantly (medians 1.4 v 0.4 mmol/l/h, p < 0.05) during the first month of
      treatment. The five and eight month values were intermediate (medians 0.8 and 0.7
      mmol/l/h, respectively). These changes were not significant compared with the
      baseline or the one month areas. Similar changes were seen in both treatment
      groups. Neither treatment had any significant effect on plasma cortisol in the
      one hour adrenocorticotrophic hormone test. CONCLUSIONS: In patients stressed by
      uncontrolled asthma, the antiasthmatic effect of high dose beclomethasone
      dipropionate and budesonide was accompanied by a significant initial decrease in
      insulin resistance with a parallel improvement in glucose tolerance. During
      prolonged treatment a small increase in insulin sensitivity was found. The
      overall effect of beclomethasone dipropionate and budesonide inhalations on
      carbohydrate metabolism may be beneficial in patients with uncontrolled asthma.

PMID- 8256244
TI  - Sternomastoid muscle fatigue and twitch maximum relaxation rate in patients with
      steroid dependent asthma.
AB  - BACKGROUND: Long term oral corticosteroid treatment is a cause of myopathy of the
      skeletal muscles. The effect of long term treatment with oral corticosteroids on
      the respiratory muscles is uncertain. Respiratory muscle function and fatigue in
      sternomastoid muscle were investigated in a group of patients with chronic severe
      asthma who were taking oral corticosteroids. The results were compared with those
      from a group of patients with chronic airflow limitation who were not taking oral
      steroids. METHODS: Twelve patients with chronic severe asthma, taking a mean
      daily dosage of 8 mg of prednisolone for a mean (SD) of 16.8 (9.1) years, were
      compared with patients with chronic airflow limitation and individually matched
      for sex, age, and severity of airflow limitation. Lung function tests, maximal
      mouth pressures, and quadriceps and sternomastoid muscle strength were measured.
      The sternomastoid muscle was fatigued by maximal headlift exercise to 70% of
      initial headlift force and the endurance time noted. Sternomastoid fatigue was
      assessed by twitch maximum relaxation rate (TMRR) measured in the fresh state and
      for 30 minutes after exercise. RESULTS: There was no significant difference
      between the control group and the corticosteroid group for maximal mouth
      pressures, fresh state TMRR, and quadriceps and sternomastoid strength. The
      control group had a significantly longer mean (SD) endurance time than the
      corticosteroid group (121 (47) s v 86 (24) s), and also had significantly less
      slowing and faster recovery of the TMRR after exercise. The slowing and recovery
      of the TMRR in the corticosteroid group, however, was similar to that previously
      reported for normal subjects. CONCLUSION: Respiratory muscle weakness does not
      occur more often in patients taking oral corticosteroids. The corticosteroid
      group was more prone to fatigue than the control group, but was similar to normal
      subjects. This suggests that chronic airflow limitation may produce a training
      effect on the respiratory muscles that might be attenuated by long term oral
      corticosteroid treatment.

PMID- 8256245
TI  - Correction of glutathione deficiency in the lower respiratory tract of HIV
      seropositive individuals by glutathione aerosol treatment.
AB  - BACKGROUND: Concentrations of glutathione, a ubiquitous tripeptide with immune
      enhancing and antioxidant properties, are decreased in the blood and lung
      epithelial lining fluid of human immunodeficiency virus (HIV) seropositive
      individuals. Since the lung is the most common site of infection in those who
      progress to AIDS it is rational to consider whether it is possible to safely
      augment glutathione levels in the epithelial lining fluid of HIV seropositive
      individuals, thus potentially improving local host defence. METHODS: Purified
      reduced glutathione was delivered by aerosol to HIV seropositive individuals (n =
      14) and the glutathione levels in lung epithelial lining fluid were compared
      before and at one, two, and three hours after aerosol administration. RESULTS:
      Before treatment total glutathione concentrations in the epithelial lining fluid
      were approximately 60% of controls. After three days of twice daily doses each of
      600 mg reduced glutathione, total glutathione levels in the epithelial lining
      fluid increased and remained in the normal range for at least three hours after
      treatment. Strikingly, even though > 95% of the glutathione in the aerosol was in
      its reduced form, the percentage of oxidised glutathione in epithelial lining
      fluid increased from 5% before treatment to about 40% three hours after
      treatment, probably reflecting the use of glutathione as an antioxidant in vivo.
      No adverse effects were observed. CONCLUSIONS: It is feasible and safe to use
      aerosolised reduced glutathione to augment the deficient glutathione levels of
      the lower respiratory tract of HIV seropositive individuals. It is rational to
      evaluate further the efficacy of this tripeptide in improving host defence in HIV
      seropositive individuals.

PMID- 8256246
TI  - Isolation of mycobacteria from patients seropositive for the human
      immunodeficiency virus (HIV) in south east England: 1984-92.
AB  - BACKGROUND: Tuberculosis and other mycobacterial infections are well recognised
      complications of HIV infection and surveillance is thus required. METHODS: All
      mycobacteria isolated from HIV positive subjects and referred to the Public
      Health Laboratory Service South East Regional Tuberculosis Centre (SERTC) from
      the first such case in 1984 until the end of 1992 were reviewed. RESULTS: A total
      of 803 mycobacteria isolated from 727 HIV positive subjects were referred to the
      SERTC during the study period. A single species was isolated from 660 patients:
      150 members of the tuberculosis complex (146 M tuberculosis, two M bovis, and two
      M africanum), 356 M avium-intracellulare (MAI), and 154 other environmental
      mycobacteria. More than one mycobacterium was isolated from 67 patients. In 12
      cases M tuberculosis and MAI were isolated from the same patient, almost always
      in that sequence, with an interval of 8-41 months between isolations. Most of the
      407 isolates of MAI (74%) were considered to be clinically significant and often
      caused disseminated disease. In other cases single isolates of MAI were obtained
      from sputum or faeces and occasionally such isolates preceded disseminated
      disease by several months. Only 33 (14%) of the 229 isolates of environmental
      mycobacteria other than MAI were considered clinically significant. CONCLUSIONS:
      HIV related mycobacterial disease is increasing in incidence in south east
      England. Further studies are required to determine the significance of single
      isolates of MAI and other environmental mycobacteria as a guide to the need for
      preventive chemotherapy or immunotherapy.

PMID- 8256247
TI  - Histologically atypical Pneumocystis carinii pneumonia.
AB  - BACKGROUND: Infection with Pneumocystis carinii typically results in a pneumonia
      which histologically is seen to consist of an eosinophilic foamy alveolar exudate
      associated with a mild plasma cell interstitial infiltrate. Special stains show
      that cysts of P carinii lie within the alveolar exudate. Atypical histological
      appearances may occasionally be seen, including a granulomatous pneumonia and
      diffuse alveolar damage. In these patients the clinical presentation may be
      atypical and results of investigations negative unless lung biopsies are
      performed and tissue obtained for histological examination. METHODS: The
      incidence and mode of presentation of histologically atypical pneumocystis
      pneumonia was studied in a cohort of HIV-I antibody positive patients. RESULTS:
      Over a 30 month period 138 patients had pneumocystis pneumonia, of whom eight
      (6%) had atypical histological appearances which were diagnosed (after negative
      bronchoalveolar lavage) by open lung biopsy in five, percutaneous biopsy in one,
      and at post mortem examination in two. Atypical appearances included
      granulomatous inflammation in four patients, "pneumocystoma" in two (one also had
      extrapulmonary pneumocystosis), bronchiolitis obliterans organising pneumonia in
      one patient, diffuse alveolar damage and subpleural cysts in one (who also had
      intrapulmonary cytomegalovirus infection), and extrapulmonary pneumocystosis in
      two patients. CONCLUSIONS: Various atypical histological appearances may be seen
      in pneumocystis pneumonia. Lung biopsy (either percutaneous or open) should be
      considered when bronchoalveolar lavage is repeatedly negative and evidence of P
      carinii should be sought, by use of special stains, in all lung biopsy material
      from HIV-I antibody positive patients.

PMID- 8256248
TI  - [Latency of Brucella abortus causes problems in oriented control: a review].
AB  - This review on Brucella abortus in cattle covers the pathogenesis, the
      epidemiology and the diagnostics of brucellosis. Emphasis is given to the
      presence of latent infections in young stock. Calves infected by B. abortus in
      utero or after ingestion of infected milk may acquire a persistent infection.
      These animals might present a significant problem in brucellosis control and
      eradication schemes, since they are difficult to detect by the usual serological
      tests as they remain negative until near the first calving or abortion. The
      diagnostics must be improved: (new) tests need to be made more sensitive and
      herds and/or animals should be tested more frequently after introduction of
      cattle into a herd. Moreover more attention should be paid to cases of abortion.
      It is also suggested that if the slaughter of infected herds is limited to adult
      animals, the heifer calves could be a source of infection to the restocked herd.

PMID- 8256249
TI  - [Perinatal mortality and the birth of weak calves].
AB  - In this review article the problem of perinatal mortality and the birth of weak
      calves is discussed. Two main causes can be distinguished: hypoxia and
      infections. It is emphasized that for a correct diagnosis a combination of a
      comprehensive anamnesis, a thorough examination of the calf and a laboratory
      investigation is necessary. Treatment of weak calves is in many cases
      disappointing. Preventive measures as an excellent management of periparturient
      cows are important.

PMID- 8256250
TI  - [Cats after sterilization].

PMID- 8256251
TI  - [Counting of unborn lambs in sheep using echography].

PMID- 8256252
TI  - [Chicken vaccine].

PMID- 8256253
TI  - The synthesis of estriol 16- and 17-monoglucuronide from estriol.
AB  - An efficient and convenient procedure for the synthesis of estriol 16- and 17
      monoglucuronides from estriol is described. This is achieved by the selective
      protection and deprotection of the hydroxy groups in estriol, Koenigs-Knorr
      reactions with methyl 1-bromo-1-deoxy-2,3,4-tri-O-acetyl-alpha-D
      glucopyranuronate and subsequent hydrolysis. The products have been characterized
      by proton nuclear magnetic resonance (1H NMR), two-dimensional 1H homonuclear
      shift-correlated spectra (2D-COSY) and mass spectra. The selective Koenigs-Knorr
      reaction of the alcoholic hydroxyl group in the presence of a phenolic hydroxyl
      group is also reported.

PMID- 8256254
TI  - Anticoagulant and estrogenic effects of two new 17 beta-aminoestrogens, butolame
      [17 beta-(4-hydroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol] and pentolame [17
      beta-(5-hydroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol].
AB  - The syntheses and characterizations of two new 17 beta-aminoestrogens, butolame
      [17 beta-(4-hydroxy-1-butylamino)-1,3,5(10)-estratrien-3-ol] and pentolame [17
      beta-(5-hydroxy-1-pentylamino)-1,3,5(10)-estratrien-3-ol], are presented. Both
      compounds, when administered in single subcutaneous injections to male mice and
      rats, produce dose-dependent increases in blood clotting times that may last
      several days. The estrogenic effects assessed by the vaginal cornification test
      are of relatively short duration.

PMID- 8256255
TI  - Photoaffinity labeling of chick intestinal 1 alpha,25-dihydroxyvitamin D3
      receptor.

PMID- 8256256
TI  - Effect of ovariectomy followed by administration of ovarian steroid hormones on
      the pig pinealocyte ultrastructure.
AB  - The ultrastructure of female pig pinealocytes was studied after ovariectomy alone
      and ovariectomy followed by administration of estradiol, progesterone, or both.
      Administration of estradiol as well as a combination of estradiol and
      progesterone induced qualitative ultrastructural changes in pinealocytes relative
      to Golgi apparatus and cytoplasmic dense bodies as well as quantitative ones,
      such as a decrease in relative volume of cytoplasmic dense bodies and lysosomes.
      Administration of progesterone caused the formation of dense bodies and a
      decrease in the relative volume of lysosomes. The results point to a relationship
      between the pineal gland and gonads in the pig and suggest that gonadal steroids,
      particularly estradiol, could be involved in a feedback mechanism of the
      hypothalamic-hypophyseal-gonadal system to the pineal gland.

PMID- 8256257
TI  - Phospholipid requirement of epididymal testosterone 5 alpha-reductase and
      phospholipid composition of epididymal microsomes.
AB  - We have investigated phospholipid requirement for testosterone 5 alpha-reductase
      solubilized from microsomal and nuclear fractions of rat epididymis. The 5 alpha
      reductase from microsomal fraction was stimulated by phosphatidylcholine (PC)
      with long acyl-chain lengths, but inhibited by short chain PC. The nuclear enzyme
      activity was weakly activated by PC with various acyl-chain lengths tested.
      Synthetic phosphatidylserine (PS), such as dioleoylPS, most strongly stimulated
      the microsomal enzyme activity, but did not exhibit any activation of the nuclear
      enzyme activity. Endogenous phospholipids, such as PC, PS, and
      phosphatidylethanolamine (PE) separated from bovine epididymal microsomes were
      tested for their stimulatory effects on microsomal and nuclear enzymes. Among
      these endogenous phospholipids, PS most greatly stimulated the microsomal 5 alpha
      reductase activity, whereas both PC and PE weakly activated the enzyme activity.
      On the other hand, endogenous PC and PS had no ability to support the nuclear
      enzyme activity. The fatty acid compositions of PC and PS from bovine epididymal
      microsomes were determined, in order to elucidate the relationship between 5
      alpha-reductase activation by these phospholipids and the structure of their acyl
      chains. The relative content of fatty acids in PC, in a decreasing order, was
      palmitate > linoleate > oleate; that in PS was stearate > oleate > palmitate.
      Based on these observations, the roles of microsomal PS and PC in epididymal 5
      alpha-reductase reaction will be discussed.

PMID- 8256258
TI  - Nuclear receptors for progesterone and estradiol in the guinea pig uterine
      compartment during gestation.
AB  - Because progesterone suppresses myometrial contractility, the assumption is often
      made that the withdrawal of this steroid is a prerequisite for parturition.
      However, steroid patterns in maternal blood of the guinea pig do not consistently
      change with impending parturition and it has been claimed that progesterone does
      not suppress guinea pig myometrial contraction. The present study investigated
      progesterone and estrogen nuclear receptor binding in myometrium, endometrium,
      and chorion between 32 days of gestation and delivery at 67-71 days. Binding
      characteristics and behavior during sedimentation in sucrose density gradients
      were typical of the steroid hormone receptor family. Decreased progestin binding
      occurred in the myometrium, from a high of 1600 fmol/mg DNA at 49-51 days to a
      low of 450 fmol/mg DNA (P < 0.01) on the day of detectable pubic relaxation. This
      decrease commenced at 60-63 days just before the onset of relaxation. A similar,
      though less well defined change occurred in endometrium. Estradiol nuclear
      receptor binding in myometrium remained at about 350 fmol/mg DNA from 32 days
      until 1-2 days pre-partum when it increased to about 650 fmol/mg DNA (P < 0.05).
      Estradiol binding in endometrium showed an inconsistent pattern and chorion
      binding for both progestin and estradiol was low and unremarkable. We conclude
      that there is a potential for decreased progesterone effect in myometrium at
      about one week before delivery and increased estrogen action in that tissue
      immediately before delivery.

PMID- 8256259
TI  - Transformation of cholic acid by Arthrobacter simplex.
AB  - Fermentation of cholic acid with Arthrobacter simplex (IICB 227) under aerobic
      conditions yielded 3,12-dioxo-23,24-dinorchola-4,6-dienoic acid, 7 alpha-hydroxy
      3,12-dioxo-23,24-dinorchol-4-enoic acid, 3 alpha, 7 alpha-dihydroxy-12-oxo-5 beta
      cholan-24-oic acid, 3 alpha, 7 alpha-dihydroxy-12-oxo-5 beta-23,24-dinorcholan-22
      oic acid, 7 alpha, 12 alpha-dihydroxy-3-oxo-5 beta-cholan-24-oic acid, 7 alpha-12
      alpha-dihydroxy-3-oxo-4-cholenoic acid, 7 alpha, 12 alpha-dihydroxy-3-oxo-23,24
      dinorchol-4-enoic acid, and methyl-3 alpha-7 alpha, 12 alpha-trihydroxy-5 beta
      cholan-24-oate in addition to a new metabolite 2 beta-hydroxy-3,12-dioxo-23,24
      dinorchola-4,6-dienoic acid. Each microbial metabolite was characterized by the
      application of various spectroscopic methods. The availability of some of the
      metabolites' enabled complete elucidation of their 13C NMR spectra.

PMID- 8256260
TI  - Na+/H+ exchange and PLA2 activity act interdependently to mediate the rapid
      effects of 1 alpha, 25-dihydroxyvitamin D3.
AB  - 1 alpha, 25-Dihydroxyvitamin D3 (1 alpha, 25-(OH)2D3) has been shown to rapidly
      increase cytosolic calcium in freshly isolated and cultured rat hepatocytes. The
      rise in cytosolic calcium is dependent on phospholipase A2 (PLA2) activation and
      cell alkalinization through the Na+/H+ antiport system. To further characterize
      the rapid effects of 1 alpha, 25-(OH)2D3, cultured hepatocytes were treated with
      inhibitors of PLA2 and the Na+/H+ antiport system. 1 alpha, 25-(OH)2D3 treatment
      caused a 31-66% increase in [32P]lysophosphatidylinositol (LPI) and a 0.04
      increase in pH within 5 minutes. Inhibition of the Na+/H+ antiport system with
      amiloride or removal of extracellular sodium abolished the 1 alpha, 25-(OH)2D3
      rise in LPI. Inhibition of PLA2 with bromophenacylbromide also blocked the 1
      alpha, 25-(OH)2D3-induced rise in [32P]LPI and cytosolic alkalinization in
      response to 1 alpha, 25-(OH)2D3. The data indicate that 1 alpha, 25-(OH)2D3
      rapidly increases the activity of PLA2 and the Na+/H+ antiport system. The
      production of LPI is dependent on PLA2 activation and cell alkalinization through
      the Na+/H+ antiport system. It appears that the two events are interdependent in
      hepatocytes.

PMID- 8256261
TI  - Synthesis and characterization of the 6 alpha- and 6 beta-hydroxylated
      derivatives of corticosterone, 11-dehydrocorticosterone, and 11-deoxycortisol.
AB  - This report describes the synthesis of 6 alpha, 17,21- and 6 beta, 17,21
      trihydroxypregn-4-ene-3,20-dione, 6 alpha, 7,21- and 6 beta, 11 beta, 21
      trihydroxypregn-4-ene-3,20-dione, and--for the first time--that of 6 alpha, 21-
      and 6 beta, 21-dihydroxypregn-4-ene-3,11,20-trione. The former four compounds
      were prepared by 6-hydroxylation of 17,21-trihydroxypregn-4-ene-3,20-dione and 11
      beta, 21-dihydroxypregn-4-ene-3,20-dione, respectively. This was achieved by
      autoxidation or by oxidation with 3-chloroperbenzoic acid, of the 3-methoxy
      pregna-3,5-dienes of the latter two steroids. The yield of the 6 beta
      hydroxylated steroids, but not of their corresponding 6 alpha-epimers, was higher
      using autoxidation than the peracid. The two 6-hydroxylated pregnenetriones were
      prepared from 6 alpha, 21-diacetoxy-11 beta-hydroxypregn-4-ene-3,20-dione and 6
      beta, 21-diacetoxy-11 beta-hydroxypregn-4-ene-3,20-dione, respectively, by
      oxidation with pyridinium chlorochromate. The above-mentioned six steroids were
      identified and characterized by nuclear magnetic resonance, infrared,
      ultraviolet, high performance liquid chromatography, gas chromatography, and mass
      spectrometry.

PMID- 8256262
TI  - Mechanisms of translocation of proteins across membranes.

PMID- 8256263
TI  - The intermediate compartment between endoplasmic reticulum and Golgi complex in
      mammalian cells.

PMID- 8256264
TI  - The endoplasmic reticulum as a site of protein degradation.

PMID- 8256265
TI  - The endoplasmic reticulum is the site of lipoprotein assembly and regulation of
      secretion.

PMID- 8256266
TI  - Components and mechanisms involved in transport of proteins into the endoplasmic
      reticulum.

PMID- 8256267
TI  - Endoplasmic reticulum and the control of Ca2+ homeostasis.

PMID- 8256268
TI  - Antigen processing and presentation. The role of the endoplasmic reticulum.

PMID- 8256269
TI  - Distribution, biosynthesis, and function of mevalonate pathway lipids.

PMID- 8256270
TI  - Phospholipid translocation in the endoplasmic reticulum.

PMID- 8256271
TI  - Cytochrome P-450 in the endoplasmic reticulum. Biosynthesis, distribution,
      induction, and degradation.

PMID- 8256272
TI  - NADH-cytochrome b5 reductase and cytochrome b5. The problem of posttranslational
      targeting to the endoplasmic reticulum.

PMID- 8256273
TI  - Motility and construction of the endoplasmic reticulum in living cells.

PMID- 8256274
TI  - Folding, assembly, and posttranslational modification of proteins within the
      lumen of the endoplasmic reticulum.

PMID- 8256275
TI  - Biological functions and biosynthesis of glycolipid-anchored membrane proteins.

PMID- 8256276
TI  - Membrane cycling between the ER and Golgi apparatus and its role in biosynthetic
      transport.
AB  - Membrane traffic between the ER and Golgi is now recognized as a carefully
      regulated process controlled by distinct anterograde (to the Golgi) and
      retrograde (to the ER) pathways. These pathways link two organelles with
      different morphologies, structures, and localizations within the cell. The ER,
      which is involved in multiple cellular functions including protein biosynthesis
      and folding, extends to the cell periphery and forms a dynamic tubule reticulum.
      By contrast, the Golgi apparatus, which functions in membrane sorting and
      recycling events, is localized at the center of the cell near the MTOC and is
      comprised of compact cisternal units. The required transport into the Golgi
      apparatus of newly synthesized proteins exported from the ER offers a twofold
      advantage to the cell. First, the rate of movement of membrane and protein
      through the biosynthetic pathway can be controlled by the selective use of a
      recycling pathway. Second, membrane moving through the biosynthetic pathway
      enters a structure specialized for sorting of membrane to different final
      destinations in the cell Control of biosynthetic transport within the ER/Golgi
      system involves the utilization of two alternative transport pathways:
      anterograde (ER to Golgi) and retrograde (Golgi to ER). These two pathways share
      a common regulatory system involving membrane assembly/disassembly of cytosolic
      coatomer proteins. Thus, conditions that favor irreversible coatomer binding
      (i.e., GTP gamma S) inhibit retrograde transport while producing anterograde
      transport intermediates. Conditions that prevent coatomer binding (i.e., BFA)
      inhibit anterograde transport and enhance retrograde transport. The underlying
      biochemical machinery that normally balances anterograde and retrograde membrane
      traffic between the ER and Golgi is only just beginning to be understood. Any
      model to explain this system, however, must account for the morphologic
      characteristics of the membranes involved. Whereas anterograde traffic involves
      discontinuous "coated" structures moving from peripheral sites in the ER toward
      the central Golgi, retrograde traffic utilizes continuous "noncoated" tubule
      structures that move from a central site (i.e., the CGN) to the peripheral ER
      (see Figure 3). Such a system maximizes volume transport (utilizing vacuolar
      structures) in the anterograde direction and membrane transport (utilizing
      tubules) in the retrograde direction. It is therefore ideal for sorting of bulk
      flow lumenal contents from recycling membrane early in the biosynthetic pathway.

PMID- 8256277
TI  - [Cardiovascular diseases in the elderly: living longer but more illnesses?].

PMID- 8256278
TI  - [Longitudinal study in the elderly in The Netherlands: an inventory focused on
      policy relevance].
AB  - With the purpose of gathering policy relevant information on changes in
      functioning of older persons, in 1989/1990 an inventory was made of longitudinal
      research in the Netherlands in which data on the older population are collected.
      The inventory resulted in a list of over thirty studies in a wide range of
      disciplines. The stage of these studies was updated in mid-1992. In this paper,
      the studies are categorized according to ten themes relevant to the policy on
      aging. The themes are based on the Lalonde model of prevention and on the WHO
      classification of impairments-disabilities-handicaps, which were extended to the
      full life sphere of older persons. Each study is briefly described. For each
      theme is indicated what contribution the existing research can make to the policy
      relevant information sought. It is concluded that thus far no comprehensive,
      multidisciplinary study was available which can provide integrated information on
      changes in functioning of older adults.

PMID- 8256279
TI  - [Public information on normal forgetfulness and dementia: effectiveness of a
      systematically developed information pamphlet].
AB  - Previous research revealed that many elderly people are worried about their
      memory and are afraid of falling victim to dementia. An information brochure was
      developed in 1991 for this target group. After reading the brochure, 63% of all
      respondents who were worried about dementia beforehand (n = 307), said that their
      anxiety had decreased or disappeared. Approximately 3% of the total group of 400
      respondents became more worried. A cognitive test battery was used to determine
      whether people's increased or decreased anxiety was justifiable. This test
      battery gave an indication of the severity of cognitive problems. A sample of 104
      people was tested. Thirty subjects achieved a low test score and sixteen of them
      were inappropriately reassured by the brochure. Approximately 64% of fifty-four
      subjects who performed well on cognitive test and were worried about dementia
      beforehand, were rightly reassured, but the other 36% were (still) unnecessarily
      worried. The occurrence of dementia in a close relative covaried with worries
      about possible dementia in people with good test results. In conclusion, it
      appeared that an information brochure about normal forgetfulness and dementia may
      reduce the anxiety for dementia.

PMID- 8256280
TI  - [The role of general or regional anesthesia in the etiology of cognitive
      disorders in elderly subjects. Literature review].
AB  - In the eighties and nineties, eighteen papers were published concerning the
      influence of general or regional anaesthesia on mental function of elderly
      patients. In both groups mental changes can be found in the immediate post
      operative period, but not on the long term. Analysis of these studies shows a
      relation between postoperative mental changes and, for example, high doses of
      drugs, a low preoperative level of mental performance or other factors,
      associated with personality and environment of the patient.

PMID- 8256281
TI  - Is the slow exchange core the protein folding core?

PMID- 8256282
TI  - The tertiary structure of tRNA and the development of the genetic code.

PMID- 8256283
TI  - Co-translational protein import into mitochondria: an alternative view.
AB  - Recent in vitro and in vivo experiments suggest that the synthesis and import of
      mitochondrial proteins are very tightly coupled and that a co-translational
      import reaction may be mandatory for some proteins. These results are entirely
      consistent with early experiments which suggested that import occurs co
      translationally and that cytosolic polysomes synthesizing mitochondrial proteins
      are bound to protein import sites on isolated mitochondria. This article
      discusses and seemingly contradictory reports concerning the involvement of co
      translational and post-translational mechanisms in the import process and
      examines the impact of recent developments in the field.

PMID- 8256284
TI  - On the origin of enzymatic species.
AB  - The diversity of enzyme catalytic function is remarkable, particularly when one
      considers that ancestral life forms must have started with a much smaller
      ensemble of proteins. In this article, we discuss the evolution of the mandelate
      pathway in pseudomonads as an example of how catalytic diversity may have
      evolved. We suggest that existing enzymes that catalyse the chemistry needed to
      accomplish a transformation were recruited, followed by the evolution of specific
      binding.

PMID- 8256285
TI  - Amino acid sequence similarity between CL100, a dual-specificity MAP kinase
      phosphatase and cdc25.

PMID- 8256286
TI  - Related GAP domains in inositol polyphosphate 5-phosphatase and the p85 subunit
      of phosphatidylinositol 3-kinase.

PMID- 8256287
TI  - Beat the clock: paradigms for NTPases in the maintenance of biological fidelity.
AB  - Kinetic proofreading is a strategy used by cells to reduce the number of errors
      made when replicating and expressing genetic information. Recent advances in mRNA
      splicing suggest a variation on the theme of previously described kinetic
      proofreading mechanisms, which may apply to other multicomponent assembly
      processes in the cell.

PMID- 8256288
TI  - Transduction of binding energy into hemoglobin cooperativity.
AB  - Hemoglobin is a tetrameric molecule consisting of two identical alpha beta dimers
      which assemble into either of two quaternary structures, T or R. Recent studies
      on mutant and partially ligated hemoglobins have revealed that cooperativity
      exists between the alpha and the beta hemes of each dimeric half-molecule and
      have led to a symmetry rule for quaternary T-->R switching: the quaternary R
      structure is energetically favored over the T structure when each dimeric half
      molecule contains at least one ligated subunit.

PMID- 8256289
TI  - Rendering a membrane protein soluble in water: a common packing motif in
      bacterial protein toxins.
AB  - The recently determined structures of three different protein toxins by X-ray
      crystallography has unexpectedly revealed a common membrane-insertion domain.
      This domain consists of an alpha-helical bundle of between seven and ten helices,
      some of which are hydrophobic. The three toxins, colicin, insecticidal delta
      endotoxin and diphtheria toxin are directed towards different hosts, have
      different killing mechanisms and bear no sequence homology. The observation of a
      common membrane-insertion domain has implications for the design of therapeutic
      agents in combating disease.

PMID- 8256290
TI  - Eukaryotic membrane traffic: retrieval and retention mechanisms to achieve
      organelle residence.
AB  - The localization of integral membrane proteins to specific organelles is
      necessary to maintain the functional integrity of eukaryotic cells. Recent
      studies indicate firstly, that retrieval and retention mechanisms, requiring
      specific primary sequence motifs, are used to ensure that proteins reside in
      specific membranes of the secretory and endocytic pathways and secondly, that
      these membranes exist as components of two juxtaposed systems separated by the
      cisternae of the Golgi stack.

PMID- 8256291
TI  - Networking on the internet.

PMID- 8256292
TI  - An ultrastructural study of six cases of chronic active C hepatitis. A comparison
      with chronic active B hepatitis.
AB  - Liver biopsies from six patients affected by chronic active hepatitis (CAH)
      induced by hepatitis C virus (HCV) have been investigated ultrastructurally and
      their features compared with those of five cases of CAH induced by hepatitis B
      virus (HBV). Clusters of deeply packed nuclear inclusions (18 to 22 nm in
      diameter) were found in patients with HCV-CAH. They were irregularly round and
      ill-delimited. These inclusions were distinct from the regular round and well
      delimited nuclear inclusions associated with HBV. HCV-associated nuclear
      inclusions were similar to a peculiar type of intranuclear particle described in
      non-A, non-B hepatitis before the HCV disease had been recognized as a distinct
      entity. These inclusions have never been hitherto reported in infections caused
      by HBV or other known hepatotropic viruses. Together, these data suggest that the
      occurrence of these inclusions can be related to HCV activity in hepatocytes.
      Changes in the microarchitecture of the liver cell and its microenvironment were
      similar in HCV- and HBV-CAH. They were heterogeneous in different cases and did
      not display a clear correlation with the severity of the disease.

PMID- 8256293
TI  - Malignant mixed exocrine-endocrine tumor of the pancreas with unusual
      intracytoplasmic inclusions.
AB  - A case of malignant mixed exocrine-endocrine tumor of the pancreas is reported.
      Electron microscopy revealed abundant neurosecretory granules in most cels.
      Zymogen granules indicating acinar differentiation were seen in a few cells.
      Ductal features, including microvilli with prominent filamentous cores and
      intracytoplasmic mucin granules, were also noted in this lesion.
      immunocytochemical strains were positive for serotonin and glucagon. Unusual
      intracytoplasmic fibrillary inclusions are described and their possible origin
      discussed.

PMID- 8256294
TI  - Ultrastructural study of a black insulinoma.
AB  - A case of black insulinoma is reported. The color was due to a cytoplasmic
      pigment. Immunostaining for neuron-specific enolase and chromogranin was positive
      in the tumor cells, and the pigment granules themselves reacted with the
      chromogranin antibody. Numerous beta cell type dense core granules as well as
      atypical granules were found by electron microscopy. An important finding was
      that the dense core granules contribute to the lipofuscin pigment formation.

PMID- 8256295
TI  - Crystalline inclusions in a subependymal giant cell tumor in a patient with
      tuberous sclerosis.
AB  - Unusual crystalline cytoplasmic inclusions were encountered in tumor cells in a
      subependymal giant cell tumor (SEGT) in a 16-year-old girl with tuberous
      sclerosis. By electron microscopy, the tumor cells demonstrated typical features
      previously described in SEGT, including abundant dense bodies, prominent Golgi
      complexes, abundant mitochondria, rough and smooth endoplasmic reticulum,
      scattered intermediate filaments and microtubules, glycogen, and rare synaptic
      contacts as well as primitive intercellular junctions. The dense bodies were
      bound by a single membrane and were round, ovoid, irregular, or cylindric in
      appearance with electron-dense homogenous content or fingerprint profiles. Of
      note was the presence of numerous cytoplasmic rhomboidal or rectangular
      crystalline inclusions akin to those seen in alveolar soft part sarcoma. These
      inclusions measured as much as 8 microns in length and had 7-nm periodicities,
      often with intersecting lamellae. Rarely, the membrane-bound dense bodies showed
      areas of similar periodicities, indicating that the crystalline inclusions are
      related to and might originate from the dense bodies. While crystalline
      inclusions have previously been described in one patient with SEGT (Bender and
      Yunis, Ultrastruct Pathol 1980; 1:287-299), the inclusions in the present case
      were a striking feature and add to the spectrum of the ultrastructural pathology
      of SEGT.

PMID- 8256296
TI  - Synthesis and in situ localization of lysosomal alpha-glucosidase in muscle of an
      unusual variant of glycogen storage disease type II.
AB  - The lysosomal alpha-glucosidase activity is reduced to 10% to 25% of the average
      control value in most late-onset cases of glycogen storage disease type II
      (GSDII). Some adult patients, however, have been identified with an exceptionally
      low (< 5%) residual enzyme activity. We have investigated one such unusual
      variant. The rate of alpha-glucosidase synthesis appeared normal but the residual
      enzyme activity was only approximately 3% in cultured fibroblasts, cultured
      muscle cells, and muscle tissue of the patient. It appeared that fully matured
      enzyme molecules were more abundantly present in muscle tissue than in cultured
      cells. The acid phosphatase activity of affected muscle fibers was enhanced due
      to an increased number of lysosomes. Lysosomes were particularly abundant in
      vacuolated areas and they contained, as judged by immunoelectron microscopy, even
      more alpha-glucosidase molecules than usual. An excessive amount of enzyme
      molecules were also observed in the endoplasmic reticulum, the site of lysosomal
      enzyme synthesis, and the cisternae were dilated. These observations suggest that
      the lysosomal system is stimulated in response to intralysosomal glycogen storage
      and onset of cellular injury. We hypothesize that the onset of gross pathologic
      abnormalities is delayed in this particular case of adult GSDII by an increased
      synthesis of lysosomal alpha-glucosidase, and as a consequence, an increased
      residual activity in storage-prone muscle fibers.

PMID- 8256297
TI  - Renal chromophobe cell carcinoma: limitations of paraffin-embedded tissue.
AB  - Chromophobe cell carcinoma of the kidney is distinguished from other renal
      cortical tumors by the ultrastructural presence of numerous cytoplasmic vesicles
      of unknown composition. Failure to detect vesicles in paraffin-embedded tissue in
      the archival material of 10 putative chromophobe cell tumors stimulated an
      investigation into the effects of fixatives and dehydrating solvents on vesicle
      integrity. We found that although vesicles are removed by dehydrating agents
      during paraffin embedding, osmium tetroxide postfixation prevents vesicle loss
      during dehydration for electron microscopy. We conclude that paraffin-embedded
      tissue is useless for histochemical studies of vesicle composition and cannot be
      employed for the ultrastructural confirmation of a histologic diagnosis of
      chromophobe cell carcinoma since the intracellular vesicles are no longer
      present.

PMID- 8256298
TI  - Use of frozen biologic material for combined light and electron microscopy.
AB  - A simple and rapid method that enables the use of unfixed frozen material for
      light and electron microscopic purposes is described. At the light microscopic
      (LM) level, unfixed cryostat sections were used for enzyme histochemistry. When
      electron microscopic (EM) inspection was needed, tissue blocks, which were stored
      at -80 degrees C, were fixed at 4 degrees C and prepared for EM according to
      standard procedures. Ultrastructural analysis of this material demonstrated that
      most morphologic aspects of normal (human pancreas and rat liver) and pathologic
      (human pancreatic adenocarcinoma and rat colon carcinoma metastases in liver)
      tissue were rather well retained. Cryostat sectioning at -25 degrees C did not
      appear to have damaging effects on the morphology. The method was applied to
      correlate enzyme histochemical (LM) data with ultrastructural (EM) aspects of
      mineralization of stroma in explants of human pancreatic adenocarcinoma grown in
      nude mice and of nonparenchymal cells around metastases of colon carcinoma in rat
      liver.

PMID- 8256299
TI  - Concentric membranous bodies and giant mitochondria in hepatocytes from a patient
      with AIDS.
AB  - The cytoplasm of hepatocytes in a liver biopsy from a patient with acquired
      immunodeficiency syndrome (AIDS) treated with sulfamethazole-trimethoprim
      contained concentric membranous bodies (CMB) and giant mitochondria. By light
      microscopy the general architecture of the liver was unaltered. By electron
      microscopy one to three CMB were present in random distribution within several
      cells in equal periportal and centrilobular localization. CMB were irregularly
      rounded or ovoid, loosely ribosome-studded lamellar whorls. Some were agranular
      or in parallel arrangement. Giant mitochondria often with paracrystalline
      inclusions were frequently in close association with CMB. Tubuloreticular
      inclusions were noted in Kupffer cell cytoplasm. Since CMB have been infrequently
      observed in human hepatocytes, are rare in nonneoplastic human liver, and have
      not been previously reported in association with AIDS, their appearance may
      relate to regenerative changes and/or sulfamethazole-trimethoprim therapy.

PMID- 8256300
TI  - Incidence and significance of oligocilia in normal and pathologic tissues.

PMID- 8256301
TI  - [Local anesthesia and sedation].

PMID- 8256302
TI  - [Dental amalgam: a toxicological evaluation].
AB  - During the latest decades the use of dental amalgam has been discussed with
      respect to potential toxic effects of the mercury component. In order to evaluate
      potential risks from this practice the recent literature is reviewed. Corrosion
      of fillings results in liberation of mercury. The absorption from this source in
      the Danish population can be estimated to be one to five micrograms/24 hrs. This
      exposure level is far below that accepted in occupational exposure and far below
      the minimum toxic level. Investigation of placental transfer of mercury has not
      provided any reason to avoid using amalgam during pregnancy. Micromercurialism or
      metal syndrome is claimed to be related to amalgam fillings. This syndrome
      consists mainly of complaints from the central nervous system, but also from
      muscles, joints and the gastrointestinal tract. The symptoms are non-specific and
      the documentation of the existence of such a syndrome related to mercury exposure
      is weak. The symptoms reported can be due to other chemical exposures, but psycho
      social conditions may also play an important role. Information on disappearance
      of symptoms after removal of fillings may be a result of a placebo effect, which
      may be suggested until controlled experiments are performed. For this reason the
      use of chelating therapy is not indicated. Allergic contact eczema observed in
      few individuals is the only problem documented in connection with the use of
      amalgam fillings.

PMID- 8256303
TI  - [Development of caries in a group of Danish school-age children after cessation
      of systematic fluoride rinsing].
AB  - In a municipality near Copenhagen, Denmark, where fortnightly fluoride rinses
      with 0.2% neutral sodium fluoride had been performed for more than a decade, 1306
      children from kindergarten through sixth grade were stratified by school and
      grade and randomly distributed into two groups. One group continued with the
      fluoride rinses, the other group had the fluoride solution replaced with
      distilled water. Both solutions were slightly flavored. One thousand and eighty
      three children completed the three-year trial. Caries was recorded clinically by
      the dentists in the municipal dental service using criteria common for the Child
      Dental Health Services, and on bitewing radiographs by one of the authors
      applying criteria developed by Grondahl et al. Permanent molars and premolars
      were included in the study. Clinically, caries increment in the two groups was
      the same, with 94% of caries lesions and fillings situated in pits and fissures.
      According to the radiographs, caries progression in the water group was higher
      than in the fluoride group. This difference was statistically significant for the
      surfaces erupting during the study (p < 0.05).

PMID- 8256304
TI  - [Aspiration pneumonia].
AB  - Pulmonary aspiration of stomach contents is a common clinical problem. Symptoms
      and consequences depend on the aspired volume, the pH and the content of food
      particles and bacteria. There are two phases following an aspiration of stomach
      contents into the lungs. The first phase is nonspecific and begins a few minutes
      after the aspiration. This phase is due to the chemical injury. The second phase
      is an inflammatory reaction. The reaction is haemorrhagic, granulocytic and
      necrotizing when the aspirate is acid (pH < 2.5). The presence of food particles
      causes granulomas. The immunological reactions are biphasic as well. The
      bacterial infection is mainly secondary to the chemical inflammation and occurs
      with an infection rate of 25-50%. The optimum management is symptomatic and
      should entail immediate endotracheal suction, aggressive ventilatory support with
      supplemental oxygen, CPAP or PEEP if indicated by clinical assessment and blood
      gas measurements, adequate fluid replacement and antibiotics if there is evidence
      of bacterial infection.

PMID- 8256305
TI  - [Hypertrophic tonsils, upper airway obstruction and cardiac complications. A
      combined otological, medical and anesthesiological problem].
AB  - Hypoventilation in children with hypertrophied tonsils can cause hypoxemia,
      hypercarbia, acidosis and pulmonary vasoconstriction resulting in cardiac
      arrhythmias or cor pulmonale. In addition, cerebral symptoms such as day-time
      hypersomnia or even seizures may be present. Early recognition of hypertrophied
      tonsils is necessary to avoid development of severe cardiac symptoms. If cardiac
      incompensation is present, medical treatment is advocated prior to tonsillectomy.
      Anaesthesia for tonsillectomy in these children is associated with special
      considerations. Preoperative sedation should be excluded, and inhalational
      induction with O2 and Halothane is recommended. On induction a difficult
      intubation should be expected.

PMID- 8256306
TI  - [Young persons sentenced to psychiatric treatment in Copenhagen].
AB  - The material consisted of 87 persons given a sentence in the years 1978 to 1987.
      Twenty-seven were under 23 years. There was no significant difference in the
      number of persons sentenced each year in the ten year period. The age of the
      patients was between 16 and 29 years with the median age being nearly 25 years.
      Most of the patients had a psychosis. The youngest group (less than 23 years) had
      a greater proportion of non-psychotic illness. Most of the patients were males.
      They had committed serious crimes and were sentenced to treatment in psychiatric
      hospitals with contact to a probation officer during out-patient treatment. Most
      of the patients were treated with neuroleptics, whereas psychotherapy, education
      and work-training were rare. The ability to attend out-patient treatment was
      generally low, and most of the patients were taken in for hospital treatment,
      according to the requirements of the sentence, because they did not keep their
      appointments. In order to increase the quality of the treatment offered it is
      recommended that special forensic psychiatric departments are established. This
      has taken place in the Copenhagen mental health hospital in 1989.

PMID- 8256307
TI  - [Hearing loss after spinal anesthesia. An audiological controlled trial].
AB  - Audiological tests were conducted on 34 patients before and after undergoing an
      operation in spinal anaesthesia. One of these patients developed a considerable
      unilateral hearing loss in the low-frequency range, which persisted until an
      epidural blood-patch was given. Unexpectedly, we also found a general small but
      significant threshold shift at 500 Hz, which has never before been described in
      the literature. The biological mechanism is discussed, and the results suggest
      that the explanation of the hearing loss could be a condition similar to
      endolymphatic hydrops, resulting from perilymphatic hypotension due to loss of
      liquor during and after the spinal anaesthesia.

PMID- 8256308
TI  - [Reversible hearing loss in the contralateral ear after surgery of acoustic
      neurinoma].
AB  - In a prospective study of 12 patients undergoing operation for acoustic neuromas,
      the hearing on the contralateral ear was tested before and systematically after
      operation. In 11 cases a perceptive loss of at least 20 dB was found at one or
      more frequencies during the first two postoperative weeks. The maximal average
      threshold decrease was 16.5 dB in the treble and 19.6 in the low frequencies.
      After three months the hearing had normalized in all cases. The loss of
      cerebrospinal fluid during operation diminishes the CSF pressure, which is then
      transmitted to the perilymph via the cochlear aqueduct, producing a transitory
      perilymphatic hypotonia and a relative endolymphatic hypertension mimicking an
      endolymphatic hydrops.

PMID- 8256309
TI  - [Cholesterol-lowering effect of a new fermented milk product in healthy 44-year
      old Danish men].
AB  - The potential cholesterol-lowering effect of a new fermented milk product was
      tested in a homogeneous group of Danish men (all 44-year-old; n = 58) in a
      randomised, double blinded and placebo-controlled study. Two hundred ml of the
      fremented milk or placebo (chemically acidified) was taken daily for six weeks.
      After these six weeks total cholesterol decreased significantly in the fermented
      milk group by -0.37 mmol/l (confidence interval: -0.51 to -0.23 mmol/l) and no
      changes were observed in the placebo group (-0.02 mmol/l) (p < 0.01). This
      decrement in total cholesterol could be completely ascribed to a reduction of LDL
      cholesterol by 10% (i.e. -0.42 mmol/l), since HDL-cholesterol and triglyceride
      were unchanged in both groups during the study. Thus, in the present short term
      study, the tested fermented milk product was able to reduce LDL-cholesterol in
      middle-aged men.

PMID- 8256310
TI  - [Granulosa cell tumor. A 30-year material from a central hospital].
AB  - During a 30-years period seventeen women were correctly diagnosed as having a
      granulosa cell tumour. Two died of the tumour, while six women died of other
      causes. No pathological features correlated to prognosis. A conservative surgical
      approach to preserve fertility is not recommended; of the three fertile women in
      our group one died of the disease and another one had two relapses within three
      years. Eleven tumours showed evidence of increased oestradiol production, and
      this proved useful as a tumour marker. Follow up is rarely performed unless
      relapse occurs.

PMID- 8256311
TI  - [T/QRS-ratio and cardiotocographic changes in the second stage of labor--related
      to fetal condition at delivery].
AB  - The T/QRS ratio of the foetal electrocardiogram (ECG) was recorded from 92 women
      in labour. Recordings to within 30 min of delivery from 55 women were available
      for analysis. There was a weak but statistically significant correlation between
      increasing mean T/QRS ratio and increasing pH/standard base excess (SBE) in the
      umbilical artery of the 55 foetuses (Spearman, respectively r = 0.28, p = 0.04
      and r = 0.29, p = 0.04); the corresponding numbers for the subgroup of 22 where
      the cardiotocogram was classified as normal being respectively r = 0.51, p = 0.02
      and r = 0.61, p = 0.003. The mean T/QRS ratio of foetuses born with an umbilical
      artery pH of > 7.15 was 0.12 (range -0.05-0.32). There was no significant
      difference in mean T/QRS ratio between foetuses born with an umbilical artery pH
      < 7.16 (n = 10) and those born with a pH > 7.15. No trend in T/QRS ratio was
      found as labour progressed. There were only three cases of metabolic acidose (SBE
      = -10.3 to -10.6 mmol/l and pH = 7.09-7.14. In two of the cases the CTG was
      abnormal and in one case intermediate; mean T/QRS ratio was normal in all three
      cases with metabolic acidosis. Abnormal CTG was able to predict an umbilical
      artery pH < 7.15 with a sensitivity of 67% and a positive predictive value of
      27%. T/QRS ratio (T/QRS = -0.05-0.25: "normal") was not able to predict a low pH.
      The chance of finding significant changes in T/QRS ratio was limited by the small
      number of foetuses with clinically significant acidosis.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8256312
TI  - [Thalidomide treatment of prurigo nodularis].
AB  - Twenty-two patients suffering from prurigo nodularis were treated with
      thalidomide 50-300 mg daily for an average of 12 months (two weeks to five
      years), following a special arrangement between the Danish Government and the
      producer Grunenthal GMBH, by which the Government took full economical
      responsibility for any claims related to the treatment. All patients received
      prior to treatment a detailed written information about all potential side
      effects from the treatment, and had by their signature acknowledged, that they
      wished to be treated. All but two of the patients had an immediate pronounced
      effect on their main symptom, the tormenting itching. The same patients had a
      significant decrease in size and numbers of skin lesions after one to two months
      of treatment. However, the therapy had to be discontinued in thirteen patients
      (59%) due to side-effects. The most important side-effect, neuropathy, was the
      reason for discontinuation of thalidomide in five patients (22%). In spite of the
      high frequency of side-effects, we consider that this treatment modality should
      still be offered to the patients with the most severe symptoms due to the
      pronounced effect on this otherwise therapy resistant disease.

PMID- 8256313
TI  - [Hip luxation caused by fibrous dysplasia of the acetabulum].
AB  - A case of monostotic acetabular fibrous dysplasia in 12 month old twin-girl is
      described. The location of the disease caused dislocation of the left hip. Open
      reduction, synovectomy and curettage of the tumor was performed. A stable
      reduction and no sign of recurrence was found at follow-up.

PMID- 8256314
TI  - [Somatization conceals emotional problems].

PMID- 8256315
TI  - [Ugeskrift--a copy journal?].

PMID- 8256316
TI  - [Local analgesics. Pharmacology, use and adverse effects].

PMID- 8256317
TI  - [Side effects of perioperative blood transfusion--still a challenge].

PMID- 8256318
TI  - [Blood transfusion increases the risk of surgical infection].
AB  - In a prospective randomized trial the frequency of infectious complications and
      natural killer cell function were investigated in 197 patients undergoing
      elective colorectal surgery and having either no blood transfusion (n = 93),
      transfusion with whole blood (n = 56), or filtered blood free from leucocytes (n
      = 48). Postoperative infections developed in 13 patients transfused with whole
      blood (23%), in one patient transfused with blood free from leucocytes (2%) and
      in two non-transfused patients (2%) (p < 0.01). Natural killer cell function was
      significantly (p < 0.001) impaired up to 30 days after surgery in patients
      transfused with whole blood. These data provide a strong case against the use of
      whole blood transfusion in patients undergoing elective colorectal surgery.

PMID- 8256319
TI  - [Optimal treatment of chronic heart failure--with particular emphasis on
      angiotensin-converting enzyme (ACE) inhibitors].
AB  - The article reviews recent discoveries about the pathophysiology of chronic heart
      failure, especially where new insights have led to new treatment strategies, with
      particular emphasis on the use of angiotensin converting enzyme inhibitors.
      Indications for referral of patients with chronic heart failure to hospital for
      further investigation or treatment are also given. It is concluded that ACE
      inhibitors represent a new era in the treatment of chronic heart failure in
      patients with isolated or for the main part systolic left ventricle dysfunction,
      and that ACE-inhibitor treatment must be regarded as a first line drug in this
      condition, along with diuretics and perhaps digoxin. Patients in NYHA class IIIb
      IV should be referred to a specialist or hospital with regard to supplemental
      cardiological investigations and initiation of ACE-inhibitor treatment, if such
      treatment has not already ben started. Patients with slight to moderate heart
      failure (NYHA class II-IIIa) should be referred as well, unless it is known that
      the cause of heart failure is an ischaemic heart condition that does not require
      operation. In the latter case, after the relevant investigations have been
      conducted, ACE-inhibitor treatment can usually be started in a general practice
      setting, bearing the usual safety regulations and contraindications in mind.

PMID- 8256320
TI  - [Screening for colorectal neoplasms. A review and recommendations].
AB  - A review is given of methods and results of screening for colorectal cancer in
      average-risk and high-risk groups. Possible methods are digital rectal
      exploration, endoscopic examination, barium enemas, faecal occult blood tests,
      tumour markers like carcinoembryonic antigen, Ca-19-9, and others, and gene
      markers. Final results of large randomized population studies with faecal occult
      blood tests are expected within the next few years, but it will probably be
      necessary to add flexible sigmoidoscopy to achieve a major reduction in mortality
      from colorectal cancer in average-risk persons. Recommendations for screening in
      high-risk groups are proposed, but strong support for these guidelines are still
      missing, an exception being first-degree relatives of individuals with familial
      adenomatous polyposis; the other high-risk groups include members of hereditary
      non-polyposis colorectal cancer families, relatives of patients with sporadic
      colorectal cancer, patients with colorectal adenomas, patients with previous
      colorectal cancer, and patients with inflammatory bowel disease.

PMID- 8256321
TI  - [Staging of colorectal cancer with the aim of optimal treatment].
AB  - Staging of colorectal cancer has become important with respect to selection of
      patients for minor surgery, major surgery and adjuvant radio- and chemotherapy.
      The most important treatment is still surgical, but the prognosis can be improved
      in some patients with adjuvant treatment, even though it involves more side
      effects. Exact staging is necessary in order to avoid overtreatment of some and
      undertreatment of others. This article critically reviews the staging systems
      used at present.

PMID- 8256322
TI  - [Fertility after conservative surgical treatment of ectopic pregnancy, evaluated
      by a randomized trial].
AB  - In order to evaluate the fertility outcome after laparoscopic surgery for ectopic
      pregnancy, randomised trial of laparoscopy versus laparotomy was performed
      between May 1987 and June 1989. The study was conducted in a clinical university
      centre, Sahlgrens Hospital. A group a 105 patients with tubal pregnancy were
      stratified with regard to risk determinants and age randomized to laparoscopy or
      laparotomy. Eighty-seven patients who desired pregnancy were evaluated for
      subsequent fertility outcome. Linear salpingotomy was performed in both groups.
      The fertility outcome after laparoscopic salpingotomy was compared with that
      following laparotomy. There was no difference between the groups in the overall
      fertility outcome. A substantially higher proportion of patients in the
      laparotomy group were subjected to adhesiolysis performed at a second-look
      laparoscopic surgery. Adhesiolysis at a second-look laparoscopy, especially after
      laparotomy, might be beneficial in selected cases and may serve to improve
      subsequent fertility.

PMID- 8256323
TI  - [Tetracycline pleurodesis in the treatment of spontaneous pneumothorax].
AB  - From 1979 to 1988 483 patients were admitted with primary spontaneous
      pneumothorax. All patients underwent thoracoscopy to identify the cause of
      pneumothorax. Chemical pleurodesis with tetracycline was performed if cysts less
      than 2 cm in diameter were found. If larger cysts were found the patient
      underwent thoractomy. In 93 patients with cysts larger than 2 cm the recurrence
      rate after thoracotomy was 4%. In 390 patients treated with intrapleural
      instillation of tetracycline, the recurrence rate was 16% (61 patients). The
      cause of recurrence in 42 patients was cysts missed at the initial thoracoscopy.
      This study has demonstrated that thoracoscopy is a reliable and safe method for
      selection of patients for chemical pleurodesis.

PMID- 8256324
TI  - [The circulating occupational medical record in the county of Roskilde].
AB  - The aim of the circulating occupational medical record (COMR) is to coordinate
      activities and documents concerning the patient who has an occupational disease.
      This new case record belongs to the patient, which solves the problems concerning
      the professional secrecy of the involved authorities. The general practitioner,
      the trade union and amongst others the safety organisation of the work place all
      have their own schematic pages in the record. The number and use of COMRs were
      studied. Postal questionnaires were sent to the primary users of the COMRs.
      Altogether 345 COMRs were started over the two year period 1989-1991. Two hundred
      and ninety-eight COMRs were evaluable. The page of the general practitioner was
      used in 90% of the records, versus 64% in the case of the unionpage and 21% in
      the case of the safety organisation. In 78% there were documents from medical
      specialists, psychologists or physiotherapists. The majority of the documents
      were from the department of occupational medicine. In half of the COMRs there
      were documents from more than four different sources. Only 76% of the patients
      were referred to the department of occupational medicine. It is recommended that
      the COMR should be extended to the whole country.

PMID- 8256325
TI  - [Ventricular fibrillation and cardiac aneurysms caused by sarcoidosis].
AB  - A 27-year-old woman presented during a football match with sudden cardiac arrest
      due to ventricular fibrillation. After electrical defibrillation the
      electrocardiogram showed sinus rhythm with left bundle branch block.
      Ventriculography, echocardiography and magnetic resonance imaging revealed an
      aneurysm in the basal part of the ventricular septum and another aneurysm on the
      anterior wall of the right ventricle. She had normal coronary arteries.
      Ventricular tachycardia was induced in the outflow tract of the right ventricle
      during electrophysiological study. She was treated surgically by aneurysmectomy
      and cryocoagulation. No ventricular tachyarrythmia could be provoked at
      postoperative electrophysiological testing. Histological examination of the right
      ventricular aneurysm showed the presence of noncaseating granulomas and scar
      tissue consistent with cardiac sarcoidosis. She had no other systemic
      manifestations of the disease. The patient was doing well and had no cardiac
      symptoms after the operation. She died suddenly of unknown cause 21 months later.
      No autopsy was performed.

PMID- 8256326
TI  - [Renal vein thrombosis in the neonatal period].
AB  - Renal vein thrombosis is a rare disease, which most often occurs in the newborn,
      in premature babies with complicated deliveries, dehydration, septicaemia or
      congenital heart defects or in neonates delivered by diabetic mothers. Renal vein
      thrombosis is due to venous stasis secondary to haemoconcentration or decreased
      renal perfusion. The typical features are a palpable flank mass, microscopic
      haematuria, thrombocytopenia, leucocytosis and fever. Ultrasonographic
      examination shows an enlarged kidney with decreased echogenicity and loss of
      corticomedullary differentiation combined with hyperechoic streaks throughout the
      kidney. In Doppler sonography the obstruction of the peripheral veins causes a
      missing or even negative diastolic flow in the renal arteries. Intravenous
      pyelography and CT demonstrate missing or delayed excretion in the enlarged
      kidney. Usually the affected kidney becomes atrophic with calcifications of the
      renal parenchyma, the renal vein or the inferior vena cava. Therapy is
      symptomatic. The prognosis is dependent on the extent of the thrombus. In 25% of
      cases the affected kidney will improve or regain its normal function.

PMID- 8256327
TI  - [Perinatal mortality in Denmark].

PMID- 8256328
TI  - [New classification of diseases. The 10th revision of the WHO classification of
      diseases will be used in Denmark after January 1, 1994].

PMID- 8256329
TI  - [Gene-related peptide in Raynaud phenomenon].

PMID- 8256330
TI  - [Decreasing quality of semen--increasing incidence of testicular cancer?].

PMID- 8256331
TI  - [Clinical trials in cancer therapy].

PMID- 8256332
TI  - [Healthy children].

PMID- 8256333
TI  - [Treatment of purulent meningitis].

PMID- 8256334
TI  - [Purulent meningitis among adults in the county of Frederiksborg. Therapeutic
      results in the period 1 January 1980--31 December 1990].
AB  - A review of 158 cases of bacterial meningitis and meningococcal sepsis in adults
      is presented. The patients were admitted during a 11-year period, from 1980-1990.
      The incidence was 5.5/100,000 adults per year, which is high. The area had
      epidemics of meningococcal disease in the years 1987 and 1989. The bacterial
      agent was meningococci in 40.5%, pneumococci in 21.5% and unknown in 27.2%. The
      overall lethality was 13.9%, highest (26%) in patients who were infected by
      pneumococci. The meningococcal relative lethality was 14%. In the period of high
      meningococcal incidence 1986-1989, we found a relative lethality of 17%. The
      overall local hospital lethality was 18.3%, which has to be compared with 11.2%
      among patients primarily admitted to the County hospital. The lethality among
      patients who underwent emergency transfer from one of the local hospitals to the
      County hospital was 20%, which is as high as in the group of patients treated
      locally. Neither of these trends lethality are statistically significant at the
      level of 5%, tested by chi square tests.

PMID- 8256335
TI  - [Meningococcal disease 1987-1989. Outbreak of serogroup B:15:P1.16 in the county
      of Frederiksborg].
AB  - Epidemiological features of an outbreak of group B:15:P1.16 meningococcal disease
      in Frederiksborg County 1987-1989 were investigated. The study comprised 149
      cases notified during the outbreak and the two preceding years. One hundred and
      fifteen were confirmed by the isolation of Neisseria meningitidis. In 1989 the
      incidence had increased to 14.1 per 100,000 population. Among group B strains,
      B:15:P1.16. accounted for 80%. The overall mortality rate was 10%. Regarding
      cases due to group B:15:P1.16 strains, a significant time-space clustering was
      demonstrated, occurring exclusively within the 10-19 year-old group. The
      prophylactic measures used included administration of rifampicin to household
      contacts. During the outbreak the proportion of secondary cases was high (six to
      fifteen percent). All secondary cases occurred outside the household, indicating
      that the household had been protected.

PMID- 8256336
TI  - [Infarction expansion and ventricular remodelling after acute myocardial
      infarction].
AB  - Infarct expansion (IE) and ventricular remodelling (VR) are interdependent
      pathophysiologic processes in the heart following acute myocardial infarction
      (AMI), and may contribute to dilatation of the left ventricle, heart failure,
      left ventricular aneurysm and/or rupture, and poor prognosis. IE and VR are
      demonstrated by echocardiography, and are usually seen with large, transmural,
      anterior AMI, hypertension and persisting occlusion of the infarct-related
      coronary artery. All myocardial tissue components are involved in IE and VR, and
      local generation of growth factors, vasoactive mediators, oxygen-derived free
      radicals, and activation of the renin-aldosterone-angiotensin system may have
      pathophysiological significance. These mechanisms can provide the opportunity for
      therapy, and evidence suggests that treatment with angiotensin converting enzyme
      inhibitors can attenuate IE and VR.

PMID- 8256337
TI  - [Intracranial angiomatous malformations].
AB  - During a four year period, 21 patients with intracranial arteriovenous
      malformations, and six with cavernous angiomas, were operated at Hvidovre
      Hospital. Of these, 16 had ruptured. There was one operative death, and five
      displayed normal perfusion pressure breakthrough during the post-operative
      course, one of these disabling. Radical surgery was performed in 21 cases, for
      the main part of the ruptured cases with ensuing good quality of life, and for
      the unruptured cases with elimination of the risk of bleeding, in addition to
      seizure control.

PMID- 8256338
TI  - [Endovascular neuroradiologic interventions. Embolization of aneurysms and
      arteriovenous malformations. Sclerotherapy of cavernous hemangiomas].
AB  - Endovascular interventional neuroradiology was introduced less than 20 years ago,
      and has since then evolved to be an established treatment. Endovascular
      embolization is particularly well-suited for treatment of patients with
      intra/extracranial arterio-venous malformations, arteriovenous fistulae and
      inaccessible arterial aneurysms. Initiated through cooperation with a French team
      we have until now at the Radiological Department, Odense University Hospital,
      treated a total of 13 patients (one year). Eight arterio-venous malformations or
      fistulae have been completely (three patients) or partially (five patients)
      occluded with Histoacryl glue. In two other patients the internal carotid artery
      has been occluded with detachable balloons. Three additional patients with an
      extracranial cavernous hemangioma have been treated with direct puncture and
      injection of sclerosing agent (Alcohol) into the lesion, with resulting shrinkage
      of the lesion in all patients. Non-intended embolization of an artery was
      observed in one case. Endovascular interventional neuroradiology, especially
      embolization, is a step forward in the treatment of delicate vascular lesions in
      the brain and face.

PMID- 8256339
TI  - [Percutaneous cholecystectomy in acute cholecystitis].
AB  - Seventy-two patients with acute cholecystitis were treated with initial
      ultrasound-guided percutaneous transperitoneal cholecystostomy (PTCS). PTCS could
      be performed in all 72 patients almost without procedure related complications,
      and subsequent elective treatment could be done in all, except three patients
      where acute cholecystectomy was necessary because of accidental catheter
      dislocation. Seven patients died of their severe underlying illness without
      relationship to PTCS or cholecystitis. Eight patients with acalculous
      cholecystitis had no further treatment after removal of the drainage catheter. It
      is concluded that PTCS is a safe method for acute drainage in patients with acute
      cholecystitis.

PMID- 8256340
TI  - [Peritonsillar abscess treated with puncture and aspiration--a prospective 3-year
      follow-up].
AB  - Forty-one selected patients were treated with needle aspiration for peritonsillar
      abscess in our department in 1988. Two patients were treated with quinsy
      tonsillectomy secondary to needle aspiration, because of failure of treatment.
      The follow-up group consisted of 39 patients and the median follow-up time was 38
      months (range 36-44 months). There were three recurrences of the abscess, and one
      patient had recurrent tonsillitis subsequent to discharge. The rate of recurrent
      tonsillitis/abscess among patients younger than 30 and 40 years was respectively
      21% (4/19) and 14% (4/28). The rate in the corresponding older age groups was 0%.
      The overall recurrence rate was 10% (4/39). Needle aspiration is suggested as
      part of a selected strategy of treatment.

PMID- 8256341
TI  - [Radioiodine therapy of thyrotoxicosis in a central hospital].
AB  - The aim of this study was to assess the results of 131-I therapy on
      hyperthyroidism. 131-I doses were individually calculated on the basis of thyroid
      gland classification, size and iodine-uptake. All patients were pretreated with
      propylthiouracil or methimazole. Seventy-nine patients treated with radio-iodine
      during the period 1.3.81-1.6.88 were followed up. The period of observation was
      12-100 months (median 57). After eight years and four months the cumulative
      incidence of hypothyroidism was 45%, being 69% for diffuse goitre, 31% for
      multinodular goitre and 24% for solitary adenoma. A Cox-analysis showed a
      significantly greater cumulative incidence of hypothyroidism in patients with
      diffuse goitre as opposed to non-diffuse. From our data we conclude that radio
      iodine therapy of hyperthyroidism with individually calculated doses of 131-I is
      a satisfactory method, assuming that patients are subjected to lifelong follow
      up.

PMID- 8256342
TI  - [Hemangioblastomas in the central nervous system].
AB  - Examples of MR findings in the central nervous system in two patients with von
      Hippel Lindau syndrome are presented. MR examination is recommended as the method
      of choice in patients with known or suspected von Hippel Lindau syndrome. Terms:
      Von Hippel-Lindau syndrome. Haemangioblastoma. Magnetic resonance imaging. MRI.
      Central nervous system.

PMID- 8256343
TI  - [Massive theophylline poisoning. A case with survival without hemoperfusion].
AB  - We describe a case of intentional acute theophylline intoxication with a very
      high theophylline level managed successfully without haemoperfusion. Treatment
      included aggressive support of the cardiovascular system and control of seizure
      activity.

PMID- 8256344
TI  - [Pregnancy-induced diabetes insipidus].
AB  - A case of transient diabetes insipidus in pregnancy occurring in a 26 year-old
      woman is reported, and possible mechanisms leading to this disorder are
      considered. Delivery of a healthy boy was uneventful after induction of labor
      with prostin, and the condition remitted spontaneously shortly after delivery,
      following a short period of exogenous desmopressin administration. A water
      deprivation test confirmed undetectable serum ADH values, presumably due to
      temporary inappropriate ADH secretion or excessive vasopressinase activity.

PMID- 8256345
TI  - [Genetic measurements in the occupational environment].

PMID- 8256346
TI  - [New therapeutic methods for childless couples when the man's quality of semen is
      strongly reduced].

PMID- 8256347
TI  - [Cytomegalovirus infection transmitted via transfusion].

PMID- 8256349
TI  - [Nickel allergy and tubal clips].

PMID- 8256350
TI  - [Athletic injuries].

PMID- 8256348
TI  - [Choice of pharmacotherapy after narco-curare electric stimulation].

PMID- 8256352
TI  - [Soccer injuries. A prospective epidemiological and socioeconomic study].
AB  - In one year 715 soccer injuries were registered and treated in the casualty ward
      of Randers City Hospital. We conducted a prospective study of these patients,
      using a questionnaire in order to determine the most common locations, types,
      mechanisms and treatments of injury. Financial costs to society and the
      individual were also examined. Finally, we compared the most common types of
      injury definition in sports medicine. According to the Abbreviated Injury Scale,
      A.I.S., 44% of the injuries were classified as minor, 46% as moderate injury and
      9% as severe. Fractures accounted for 17% of all injuries. Sprains and contusions
      were the most frequent injuries, accounting for 46% and 25% respectively. Most
      injuries (63%) were treated in the casualty ward, whilst 20% were treated as
      outpatients. 7% were admitted to the hospital immediately, and a further 2% were
      later admitted from the outpatient clinic. A total of 88% of those hospitalized
      were treated as inpatients for 1-7 days, and 12% for more than two weeks. 31% of
      all the soccer players seen in the casualty ward were absent from work, and 12%
      were absent from work for more than three weeks. 8% of the injured soccer players
      suffered loss of income. 40% had financial losses between $0-250, 40% between
      $250-750, seven per cent between $750-1,250, and 14% more than $1,250. From the
      data presented in this study, we conclude that the injury rate among soccer
      players increases with age, and the severity of the injuries is greatest in the
      oldest age groups. Soccer injuries constitute the major part of sports injuries
      seen in the casualty ward.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256351
TI  - [Handball injuries. An epidemiological and socioeconomic study].
AB  - A total of 570 injuries in handball players were prospectively registered in a
      well-defined geographical area of 124,321 inhabitants. The incidence of handball
      injuries was 46/10,000 inhabitants/year and in females (61/10,000/year) double
      that for males (31/10,000/year). Sixty-two percent of the injuries were
      distortions and sprains and 12% were fractures. A total of 7% were hospitalised
      and the loss of income because of sick leave was in total $3870. Sixty-eight
      percent of the injured handball players did not play for more than one week.
      Surprisingly, 8% of the minor injuries resulted in a risk leave of more than six
      days. Five percent of these injured quit a tournament of training after
      sustaining a handball injury.

PMID- 8256353
TI  - [Importance of thiols (SH group) in the cardiovascular system].
AB  - Reduced glutathione (GSH) is the main intracellular non-protein thiol compound.
      GSH is important in a variety of reactions including reductive processes,
      protection of cells against oxidative stress, free oxygen species and other toxic
      compounds of endogenous and exogenous origin. In the cardiovascular field, thiol
      compounds may protect against ischaemia-reperfusion injuries, regulate enzyme
      activities and modify the function of organic nitrates and vascular tone.
      Metabolic manipulation with thiol compounds (i.e. by treatment with N
      acetylcysteine or oxothiazolidine) may provide a safe method for protecting cells
      against ischaemia and may be a relevant supplement to current cardiovascular
      therapy.

PMID- 8256354
TI  - [Indications for the use of differential ventilation and selective positive end
      expiratory pressure].
AB  - In some cases of unilateral or bilateral severe lung disease, there is serious
      hypoxia despite a high level of oxygen in the inspiratory gas mixture.
      Disturbances in the ventilation/perfusion ratio (V/Q) is a major contributing
      factor to the hypoxia seen in acute lung disease. The use of positive end
      expiratory pressure (PEEP) has in some cases been shown to make this V/Q mismatch
      even worse, and the use of high levels of PEEP is known to increase the risk of
      barotrauma and to reduce cardiac output. In this article, a method is described
      which makes it possible to ventilate each lung separately in proportion to its
      expected perfusion (differential lung ventilation), with or without the use of
      PEEP to one or both lungs (selective PEEP). Because of a more uniform V/Q the
      oxygenation in unilateral as well as in bilateral lung disease is improved. The
      risk of barotrauma as well as the impact on cardiac output is reduced. The
      patient has to be intubated with a double lumen endotracheal catheter. The gas is
      delivered by two ventilators synchronized by a master-slave cable. This method
      can also be used in the operating room, when surgical procedures have to take
      place in the lateral position, in order to counteract V/Q mismatch and hypoxia.

PMID- 8256355
TI  - [Peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.
      Evaluation of cephalothin/cephalexin monotherapy as initial treatment].
AB  - To evaluate the initial antibiotic regime of cephalothin monotherapy in the
      treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis
      (CAPD), the frequency of peritonitis was registered retrospectively together with
      the frequency of recurrent episodes and change of antibiotic. A median frequency
      of 0.96 episodes per year of dialysis was found. In 24% of the episodes no
      microorganism was cultured. 82% of the microorganisms were gram-positive cocci,
      17% gram-negative rods. The frequency of recurrent episodes was 7%. The initial
      antibiotic treatment with cephalothin had to be changed in 33% of the cases due
      to microbial resistance. In another 33% the antibiotic treatment was changed to
      something with a narrower spectrum. More than one third of the resistant
      microorganisms were methicillin-resistant coagulase-negative staphylococci. With
      quick and reliable microbiological diagnostic technique that makes it possible to
      change the antibiotic treatment early, we find cephalothin to be a suitable
      initial monotherapy.

PMID- 8256356
TI  - [Finger tip injuries. A comparative study of silver sulfadiazine and fucidin
      gauze].
AB  - Eighty-eight superficial finger-tip lesions were randomized after thorough
      cleaning to either silver sulphadiazine treatment of Fucidin fusidic acid gauze.
      In the silver sulphadiazine group the wounds were covered with a non-sterile PVC
      gloce and redressed at least every third day; in the other group Fucidin gauze
      was applied and a tubigauze dressing was left in situ for ten days, after which a
      new dressing was applied. All patients were treated until healed and followed for
      at least six months after injury. Patients in the silver sulphadiazine group
      required shorter time for healing and shorter sick leave. The treatment is
      recommended because of the easy procedure and the good results.

PMID- 8256357
TI  - [Health economical benefits of personalized hospital treatment of chronic
      bronchitis].
AB  - One hundred patients (aged 48 to 89) with chronic obstructive pulmonary disease
      were allocated to receive either "personalized hospital practice" (PHP), which
      includes training in aspects of their disease, or standard hospital practice.
      Changes in "consumption" of health services per patient from one year before
      until one year after the intervention admission were evaluated in 82 (PHP group
      42, controls 40). The increase in consumption of health services after
      intervention was on average kr 15.298 per patient per year less in the PHP group
      than in the control group (p = 0.048). Consumption of general practitioner
      services was significantly increased in the control group compared with the PHP
      group (mean 95% confidence limits) kr 1346 (549-2143) versus -89 (-423-245) per
      patient per year, p = 0.001). PHP reduces the consumption of health services by
      patients with chronic obstructive pulmonary disease, probably by increasing
      patients knowledge of disease and their ability to manage themselves.

PMID- 8256358
TI  - [Iron levels in 1359 Danish women in relation to menstruation, use of oral
      contraceptives and parity].
AB  - Iron status was assessed by measuring serum ferritin and haemoglobin in a
      population survey in Copenhagen County, comprising 1359 nonpregnant women in age
      cohorts of 30, 40, 50, and 60 years; 809 were premenopausal and 550
      postmenopausal. Premenopausal women had lower serum ferritin (median 37
      micrograms/l) than postmenopausal women (median 71 micrograms/l), p < 0.0001. Of
      premenopausal women, 17.7% had ferritin < 15 micrograms/l (depleted iron stores),
      and 23.1% had ferritin levels of 15-30 micrograms/l (small iron stores).
      Corresponding figures in postmenopausal women were 3.3% and 10.3%. Iron
      deficiency anaemia (ferritin < 15 micrograms/l and haemoglobin < 121 g/l) was
      observed in 2.6% of pre- and 0.36% of postmenopausal women. After menstruations
      had ceased, there was a steep rise in ferritin levels, being most pronounced
      during the first 7 postmenopausal years. Pre- and postmenopausal multipara had
      lower ferritin than nulli- and unipara (p < 0.04), indicating that pregnancy and
      childbirth had a long lasting reducing influence on iron stores. The use of oral
      hormonal contraceptives had a marked increasing effect on iron stores, being
      correlated to the number of years the women had been taking the pill.

PMID- 8256359
TI  - [Pneumococcal bacteremia in Hvidovre Hospital 1986-1990].
AB  - The study describes 156 consecutive cases of pneumococcal bacteraemia among
      patients admitted to Hvidovre Hospital during the five-year period 1986-1990.
      Pneumococcal bacteraemia was most common in the age groups 0-4 and 50-99 years.
      The most common focus of infection was the lungs (84%). 81% had preexisting
      diseases and the most common were: Immunosuppression due to drugs, alcoholism,
      cardiovascular disease, chronic obstructive lung disease, diabetes and
      myelomatosis. Patients over 65 years of age had a higher case fatality (35%) than
      younger (12%). The overall case fatality rate was 24%. Twenty-three percent of
      cases were hospital-acquired, and associated with a case fatality of 37%.
      Pneumococcal bacteraemia was most common during the winter season and unrelated
      to influenza. Eighty-four percent of the examined isolates represented capsular
      types included in the 23-valent pneumococcal vaccine. Three percent of the tested
      strains were relatively resistant to penicillin (MIC > 0.1 microgram/ml). Despite
      antibiotic treatment, the mortality from pneumococcal bacteraemia, particularly
      in elderly, remains high. With this in mind, one may consider offering
      pneumococcal vaccination to persons over 65 years of age with chronic
      predisposing diseases.

PMID- 8256360
TI  - [Chylous ascites after surgery on the abdominal aorta].
AB  - Chylous ascites is a rare clinical condition and especially rare as a
      complication of surgical intervention. Its pathophysiology is poorly understood.
      We report a case of chylous ascites following aortic femoral bypass managed by
      conservative approaches involving multiple paracenteses, dietary restriction of
      fat and parenteral nutrition. We suggest that cases of surgically induced chylous
      ascites which do not respond to conservative treatment within a few weeks should
      have a laparatomy to close the fistula.

PMID- 8256362
TI  - [Toxic epidermal necrolysis].

PMID- 8256361
TI  - [Eosinophilic gastroenteritis].
AB  - Two case stories of eosinophilic gastroenteritis are described. Both patients
      presented with chronic diarrhoea and weight loss. The first patient had
      eosinophilic infiltration predominantly in the mucosal layer of the intestine,
      and had in addition loss of protein in the stool. The other patient had
      predominantly subserosal eosinophilic infiltration and presented with
      eosinophilic ascites. Both patients were treated with prednisolone and responded
      immediately to therapy.

PMID- 8256363
TI  - [Treatment of primary hyperlipidemia].

PMID- 8256364
TI  - [Decreased cholesterol level shortens life].

PMID- 8256365
TI  - [Vascular surgery and amputation].

PMID- 8256366
TI  - [Can vascular surgery reduce the amputation frequency? A study of amputations in
      the county of Viborg before and after establishment of an own department of
      vascular surgery].
AB  - In June 1988 a Department of Vascular Surgery was established in the County of
      Viborg, Denmark. In a retrospective study, 314 patients had 337 major amputations
      within two time periods: 1986-1987, and 1989-1990. The number of patients seen by
      a vascular surgeon rose significantly from 19% in the first period to 49% in the
      last period, and the number of amputations was concurrently significantly reduced
      by 25%. The largest reduction was observed in 1990, probably due to an increase
      of vascular reconstructions of 43%. Assuming there is a latency between
      diagnosing "critical leg ischaemia" and amputation, this will further delay the
      already convincing results showing that vascular surgery does reduce the
      frequency of amputations. All patients with suspected critical leg ischaemia or
      threatened by amputation must be seen, or at least conferred with a vascular
      surgeon.

PMID- 8256367
TI  - [Surgery of abdominal aortic aneurysm in a department of vascular surgery
      integrated into a department of general surgery--is it satisfactory?].
AB  - Seventy-two operations for abdominal aortic aneurysm (AAA), i.e 104 per mill. per
      year, were carried out by a vascular surgical unit integrated into a general
      surgical department. Mortality rate for elective operation was 3.8%, for acute
      operation without rupture 3.8% and with rupture 31.6%. Fifty percent of patients
      with rupture reached operation, which gives an overall mortality of about 66% and
      an incidence of 56 per mill. per year. Twice as many acute operations were
      carried out in this area compared to the rest of Denmark, and no haemodialysis
      demanding complications occurred. These observations suggest that short transfer
      time is an important prognostic factor when treating ruptured AAA.

PMID- 8256368
TI  - [Retinopathy in premature infants].
AB  - Retinopathy of prematurity (ROP) is a complication of very preterm birth. The
      problem is relatively common in Denmark; although only 10 infants are blinded
      each year, this represents a high incidence in international comparison. The very
      complete Danish registry of the blind may be partly responsible. The incidence
      remains high due to the increased survival rate in very preterm infants. Although
      free oxygen radical injury most likely plays a central role, it is doubtful if
      reduction of supplementary oxygen under careful monitoring can reduce the risk of
      ROP. Unfortunately, the most preterm and most unstable infants, who are at
      highest risk of ROP, are also particularly exposed to hypoxia. It is possible
      that light increases the risk, even for other reasons it is recommended to reduce
      the intensity of light in the ward or to use eye pads, at least some of the time.
      There is no effective drug prevention, in particular there is no evidence that
      vitamin E is useful. Cryotherapy, however, in the acute phase of threshold
      disease (stage 3+), can reduce the risk of permanent loss of central vision from
      about 50% to 25%. Effective screening for ROP has become part of modern
      neonatology. Diagnosis as well as cryotherapy requires particular skill and
      experience.

PMID- 8256369
TI  - [Treatment of early stage Hodgkin disease].
AB  - In early stage Hodgkin's disease the optimal choice of treatment is still an
      unresolved issue. Twenty-two randomized trials of radiotherapy alone versus
      radiotherapy plus combination chemotherapy have been carried out world-wide. The
      preliminary results of a global meta-analysis of these trials indicate that we
      still do not definitively know whether or not the early addition of prophylactic
      chemotherapy improves survival. Arguments in favour of early chemotherapy are:
      that laparotomy may be avoided, that radiation fields and doses may perhaps be
      reduced, and that the stress of experiencing a relapse is avoided in many
      patients. The major argument against early chemotherapy is: that by careful
      staging and selection of patients and by careful radiotherapy techniques the
      number of patients exposed to potentially toxic chemotherapy may be kept at a
      minimum. Recently, trials have been carried out testing chemotherapy alone,
      results are, however, conflicting. In order not to jeopardize the good results
      achieved with the standard treatments developed over the last three decades,
      newer treatment approaches should be carefully tested in large randomized trials
      before being implemented for general clinical use.

PMID- 8256370
TI  - [Non-Hodgkin lymphoma in the elderly].
AB  - Within a seven year period, 1597 newly diagnosed cases of non-Hodgkins lymphoma
      (NHL) were included in a Danish population-based NHL-register. Of these, 602
      (38%) were aged 70 or older (age range 70-94, median: 76.8) and represented the
      population defined as "elderly" patients in the present study. Their average
      annual incidence rate was 35.7/10(5), as compared to 6.6/10(5) for patients aged
      < 70 (overall annual incidence: 9.5/105). Localised cases (stage I and II) and
      extranodal manifestations were more frequent among elderly patients. The most
      common sites of extranodal involvement were stomach (21% of all extranodal cases)
      and bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases
      were found to be less frequent (p < 0.01) in elderly patients as compared to
      their younger counterparts (< 70 years), who on the other hand had a lower
      occurrence of diffuse centroblastic cases (p < 0.01). Overall seven year survival
      for the elderly patient population was 35% (median: 1.7 years), and for patients
      aged < 70 it was 57%. This difference persisted after correction for apparently
      NHL-unrelated deaths (52% vs. 66% respectively, p < 0.0001). The following poor
      prognostic factors for elderly patients were identified by multivariate analysis:
      hepatic involvement, presence of B-symptoms, high-grade histology and elevated s
      LDH. The corresponding relative risk values were respectively 2.4, 2.2, 1.9 and
      1.6.

PMID- 8256371
TI  - [Gilles de la Tourette syndrome].
AB  - Gilles de la Tourette syndrome has its onset in childhood and is characterized by
      chronic motor and vocal tics and also complex tics. It is a lifelong illness with
      shorter and longer fluctuations in its severity. During puberty an aggravation in
      number and severity of tics is often observed, while symptoms in the third decade
      are reported to fade to some extent. The syndrome is found among all social
      classes, the male to female ratio is three to one, and it is probably inherited
      as an autosomal single dominant gene with varying penetrance. Gilles de la
      Tourette syndrome was earlier thought to be rare, but during the last years less
      pronounced cases have been seen. The etiology is not known, but a relative
      dopaminergic overactivity is a likely mechanism. It is possible to treat the
      symptoms with neuroleptics.

PMID- 8256372
TI  - [Incidence of short hamstrings and leg muscles at ages 3-17 years].
AB  - In 1991, 769 children and adolescents, 98% of the pupils in the various age
      groups in seven schools and ten kindergartens on Funen, were examined. Seventy
      five percent of the boys and 35% of the girls over the age of ten proved to have
      such short hamstrings that one knee had a extension deficit without violence of >
      or = 40 degrees when the hip was flexed 90 degrees. More than 10% of the boys
      over the age of ten had an extension deficit of > or = 60 degrees. Forty-five
      children had a difference > or = 15 degrees between the two legs. The triceps
      surae muscles are too short if the corrected foot can only be pressed slowly to
      the right angle. This was found to be the case for 25-64% of the children from
      the age of three to 17. Therefore, we must conclude that it is necessary to allow
      time in kindergarten and school for the children to stretch their muscles a few
      minutes daily.

PMID- 8256373
TI  - [Long-term prognosis of patients with ulcerative colitis].
AB  - A regional inception cohort of 1161 ulcerative colitis patients was followed from
      diagnosis to the end of 1987. Follow-up rate for death and occurrence of cancer
      was 99.9%. Median observation time 11.7 years, range 0-26 years. One hundred and
      forty-one deaths were observed, 26 due to ulcerative colitis or complications
      thereof. No significant excess mortality was found after the first year, but in
      the year of diagnosis the relative risk of death was 2.4 (p < 0.001). The
      cumulative colectomy rate was 32.4% 25 years after diagnosis. The initial extent
      of disease significantly influenced the colectomy probability, being 35% in total
      colitis, 19% in substantial colitis and 9% in distal colitis within the first
      five years after diagnosis. Six patients developed colorectal cancer within the
      observation period. Compared to the expected number of 6.6 the relative risk for
      patients with ulcerative colitis was 0.9. The calculated cumulative cancer
      incidence was 3.1% after 25 years (95% confidence limits 0.0-6.8). The calculated
      lifetime risk (0 to 74 years) for development of colorectal cancer was 3.5% for
      the patients compared to 3.7% for the Danish population. We conclude that with an
      active approach to medical and surgical treatment as was practiced here, those
      patients who are left with their colon intact bear no significantly increased
      risk of colo-rectal malignancy.

PMID- 8256374
TI  - [Effect of a safe-sex campaign on women attending a clinic of venereology. Sex
      behavior and prevalence of sexually transmitted diseases in women examined at the
      Venereaklinik in Copenhagen in 1984 and 1988].
AB  - Consecutive female patients attending the Copenhagen Venereal Disease Clinic were
      interviewed about sexual behaviour in 1984 (981 women) and in 1988 (684 women).
      Details of symptoms, age at coitarche, number of sexual partners, contraceptive
      methods, and obstetric history were recorded together with the results of the
      venereological examination. A substantially higher proportion of women used
      condoms in 1988 (51%) than in 1984 (11%), but otherwise the safe sex campaigns
      had had a limited effect on the sexual behaviour in this group of women until
      1988. The prevalence of gonorrhea decreased significantly (from 22% to 6%, p <
      0.01), whereas an increase in the prevalence of genital warts was observed (from
      4% to 10%, p < 0.01).

PMID- 8256375
TI  - [Pulmonary edema after intravenous injection of eyedrops containing adrenaline].
AB  - A case of adrenaline overdose in a 27 year old male drug addict is reported.
      Following accidental injection of 20 mg adrenaline he developed pulmonary oedema
      and severe metabolic acidosis, which responded well to symptomatic treatment.

PMID- 8256376
TI  - [CYP2D6 genotype determination].

PMID- 8256377
TI  - [Is Q10 safe?].

PMID- 8256378
TI  - [The bronchodilating effect of ephedrine tablets in bronchial asthma].

PMID- 8256379
TI  - [Left-sided colonic obstruction].

PMID- 8256380
TI  - [Hartmann's procedure in the treatment of acute obstructive left-sided colonic
      cancer].
AB  - This retrospective study included all patients over a five-year period who
      underwent the Hartmann's procedure because of a malignant left-sided large bowel
      obstruction. Twenty-nine patients were treated with this procedure. The
      cumulative operative mortality was 14%, and the five-year survival was 31%.
      Intestinal continuity was restored in seven patients (24%). There were no
      anastomotic leakages. The treatment resulted in a permanent colostomy in 62% of
      the patients. The Hartmann's procedure can be employed as a treatment of
      malignant left-sided large bowel obstruction, but will cause a high frequency of
      permanent colostomy.

PMID- 8256381
TI  - [Ovarian function after premenopausal hysterectomy].
AB  - In Denmark, about 6000 hysterectomies are performed annually, and about 75% are
      performed on benign indications in women less than 50 years of age. When deciding
      on oophorectomia per occasionem, the risk of disease in the retained ovaries must
      be weighed against the advantages of continued ovarian function. The literature
      about ovarian function after hysterectomy consists predominantly of older,
      retrospective and uncontrolled investigations describing earlier menopause,
      increased frequency of climacteric symptoms and increased risk of benign ovarian
      cysts. Hysterectomy is followed by histological changes in the retained ovaries,
      but a significant reduction in the ovarian hormone production is not documented.
      Several studies have indicated that hysterectomy is followed by an increased risk
      of ischaemic heart disease, but the literature is equivocal. A possible
      explanation for the altered ovarian function after hysterectomy is reduced
      ovarian blood supply caused by the operation, but the existence of a direct
      endocrine function of the uterus can not be excluded. Solid prospective studies
      of the ovarian function following hysterectomy are needed.

PMID- 8256382
TI  - [Renal insufficiency in myelomatosis. Causes and treatment].
AB  - Renal failure is a frequent complication in multiple myeloma and it is present in
      about 50% of patients with newly-diagnosed multiple myeloma. Renal failure at the
      time of diagnosis has earlier been associated with a bad prognosis, but a better
      prognostic factor is the response to chemotherapy. In general, it is important to
      distinguish between 1) renal insufficiency at the time of diagnosis, 2) acute
      renal insufficiency and 3) chronic renal insufficiency developing during the
      course of the disease. The patients in the first two groups are treated with
      intensive therapy which is long-lasting (median four to six weeks). The improved
      function of the kidney is correlated to an improved survival. Patients developing
      chronic renal insufficiency late in the course of the disease should receive
      palliative therapy. The most important factors that provoke acute renal
      insufficiency are dehydration, hypercalcaemia and/or infection, but renal
      insufficiency is also provoked by the use of nephrotoxic drugs, hyperuricaemia
      and/or hyperviscosity. Chronic renal insufficiency is provoked by deposits of
      light chains, infiltration by plasma cells or deposits of amyloid. The treatment
      consists of elimination of the provoking factors and start of chemotherapy.

PMID- 8256383
TI  - [Conservative treatment of clavicular fractures].
AB  - The outcome of 99 clavicular fractures was examined retrospectively through a
      questionnaire and, in 20 cases, clinical examination. Primary treatment was in
      all cases a simple sling or a figure of eight bandage. The aim of the study was
      to examine prognostic factors in relation to the end-result. The fractures were
      classified, according to the roentgenograms, and the primary dislocation, primary
      shortening and secondary shortening of the shoulder were recorded. The end-result
      was expressed as the degree of pain. Statistically significantly more patients
      with group two type two fractures had a poor result. No other prognostic factors
      were found.

PMID- 8256384
TI  - [Citrate and kidney stones].
AB  - Citrate is an important naturally occurring inhibitor of calcium stone formation
      in urine. Urinary citrate excretion was examined in 43 consecutive patients with
      recurrent idiopathic calcium nephrolithiasis and in 50 normal controls by a
      specific enzymatic technique. Hypocitraturia (< 1.6 mmol/24h) was found in 14
      (33%) stone formers compared to 6 (12%) normal controls (p = 0.03). Citrate
      excretion expressed as citrate-creatinine ratio in 24 hour urine samples was
      significantly lower in the stone formers than in the healthy controls (p = 0.03),
      and significantly lower in healthy men, compared to healthy females (p = 0.006).
      There was a great variability in urinary citrate levels in both groups, and a
      considerable overlap in the urinary citrate excretion between normal subjects and
      stone formers. Factors other than urinary citrate excretion must therefore be of
      importance in the pathophysiology of calcium stone formation. Citrate-calcium
      ratio in urine proved to be a reliable index in discriminating stone formers from
      healthy subjects.

PMID- 8256385
TI  - [An analysis of 99 consecutive shifts in the selection of antibiotics used in
      therapy in a medical department].
AB  - During 208 days 2836 patients were admitted to Sundby Hospital, medical ward. A
      total of 734 antibiotic cures were initiated. About 632 (22-23%) of the patients
      had antibiotic treatment. Penicillin, ampicillin and sulfamethizole were the most
      frequently used antibiotics. The use of erythromycin was 42-50% and 64-78% of
      that of penicillin and ampicillin respectively. Antibiotic treatment was changed
      in 99 cures in 73 patients. Fifty-seven of ninety-nine (43-71%) shifts were based
      on culture or serology and 42/99 (29-57%) shifts were based on clinical
      evaluation including microscopy and urinary stix. In 26 of the latter 42 cases
      positive culture or serology was obtained after the antibiotic was changed.
      Thirteen of the 26 shifts improved treatment, six were unlucky and seven
      indifferent, thus giving a net advantage of 13-6 = 7 of 26 shifts. This net
      advantage was due to shifts from penicillin. In ten cases the antibiotic was
      shifted to erythromycin due to suspected atypical pneumonia, but only one case
      was verified. In ten antibiotic shifts in pneumonia patients the etiologic agents
      were not identified. In 4/99 shifts in 4/73 patients relevant specimens were not
      obtained. The antibiotic most often changed compared with its total use was
      ampicillin (32/152 congruent to 1/5 of initiated cures) and shifts from
      ampicillin were more often (21/32) based on culture than shifts from penicillin
      (16/36) (p < 0.1). Initial supplementation of ampicillin with aminoglycosides was
      retrospectively relevant in 13/28 cases. Cephalosporines (p < 0.001) and
      dicloxacillin (p < 0.02) were significantly more often used as second drug,
      whereas penicillin was most often used as first drug (p < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256386
TI  - [Effects of low concentrations of NO2 on alveolar permeability and glutathione
      peroxidase in healthy subjects].
AB  - Potential toxic effects of prolonged NO2 exposure below the current threshold
      limit value (TLV) were examined in 14 healthy, non-smoking adults. The subjects
      were exposed to 2,3 ppm NO2 and to clean air for five hours with a one week
      interval between exposures. Physiological and biochemical measurements were
      obtained during exposure and the following 24 hours after. A 14% decrease in
      serum glutathione peroxidase activity (GSH-Px) was observed 24 hours after the
      start of the NO2 exposure while indications of a 22% decrease in alveolar
      permeability were found 11 hours after the start. There were no indications of
      mucous membrane irritation or of decreased lung function during or after NO2
      exposures. The results support the assumption that a delayed response is a
      feature of the human reaction to NO2 even below the current TLV of three ppm, and
      they stress the importance of an extended period of observation in future NO2
      exposure studies.

PMID- 8256387
TI  - [Obstetric health care offered to Turkish immigrant women--a quality assessment].
AB  - The object of this investigation was to make a quality-assessment of the care
      offered to pregnant and delivering Turkish immigrant women by the Danish health
      care system. The quality-assessment was made as a Medical Audit using data
      obtained from relevant medical records as well as from semi-structured interviews
      with the women. Thirteen cases were evaluated among the 65 Turkish women included
      in the project by having delivered at Aarhus Kommunehospital in the period
      between April 1 and December 15 1989. In this material no severe obstetrical
      deficiencies were found, but other types of deficiencies were observed. Bad
      communication due to insufficient use of trained interpreters and to the health
      personnel's lack of knowledge about cultural background often resulted in mutual
      misunderstandings. Most of the women were examined by many different doctors and
      midwives during pregnancy and delivery. It is demonstrated, that the lack of
      continuity was an additional strain of these women. It is concluded that the
      difficulties in communication are potentially dangerous, increasing the risk of
      delayed or missing obstetrical intervention. The insufficient communication
      demonstrated causes insecurity and inappropriate care.

PMID- 8256388
TI  - [Spontaneously bleeding renal hemangioma treated by embolization].
AB  - Until 1990, a total of 198 cases of renal haemangiomas have been reported; these
      patients often have to undergo partial or total nephrectomy. We report a case of
      a 37 year old female admitted with severe haematuria. Selective renal angiography
      revealed a haemangioma with arteriovenous shunting, situated centrally in her
      left kidney. Embolization of the artery supplying the shunt was performed with
      five coils, and four months later isotope renography showed that both kidneys
      were functioning equally well. The only observed side-effect was mild
      hypertension.

PMID- 8256389
TI  - [When basic research opens new ways in the treatment of cancer].

PMID- 8256390
TI  - [Withdrawal of antihypertensive treatment].

PMID- 8256391
TI  - [Withdrawal of antihypertensive treatment].

PMID- 8256392
TI  - When to operate on neonatal hydronephrosis.

PMID- 8256393
TI  - Hydronephrosis in the neonate.

PMID- 8256394
TI  - Patient-reported complications and follow-up treatment after radical
      prostatectomy. The National Medicare Experience: 1988-1990 (updated June 1993).
AB  - To estimate the probabilities of complications and follow-up treatment, a sample
      of Medicare patients who underwent radical prostatectomy (1988 through 1990) was
      surveyed by mail, telephone, and personal interview. Respondents reported their
      current status with respect to continence and sexual function as well as post
      surgical treatments they had had to treat residual or recurrent cancer or
      surgical complications. Over 30 percent reported currently wearing pads or clamps
      to deal with wetness; over 40 percent said they drip urine when they cough or
      when their bladders are full; 23 percent reported daily wetting of more than a
      few drops. About 60 percent of patients reported having no full or partial
      erections since their surgery, and only 11 percent had any erections sufficient
      for intercourse during the month prior to the survey. Six percent had surgery
      after the radical prostatectomy to treat incontinence; 15 percent had treatments
      or used devices to help with sexual function; 20 percent report having had post
      surgical treatment for urethral strictures. In addition 16 percent, 22 percent,
      and 28 percent reported follow-up treatment for cancer (radiation or androgen
      deprivation therapy) at two, three, and four years after radical prostatectomy.
      These estimates of complication and follow-up treatment rates are generally
      higher, and almost certainly more representative for older men, than estimates
      previously published. Patients and physicians may want to weight heavily the
      complications and need for follow-up treatments when considering radical
      prostatectomy for prostate cancer.

PMID- 8256395
TI  - Extra-anatomic renal revascularization in patients with renal artery stenosis and
      abdominal aortic occlusion.
AB  - Thirteen patients with atherosclerotic renal artery stenosis and total abdominal
      aortic occlusion underwent extra-anatomic surgical renal revascularization
      without aortic replacement. Renal artery stenosis was present unilaterally (n =
      2), bilaterally (n = 7), or in a solitary kidney (n = 4). Surgical renal
      revascularization was indicated for treatment of severe hypertension in all
      patients and for preservation of renal function in 10 patients. The level of
      abdominal aortic occlusion was suprarenal (n = 3), perirenal (n = 2), or
      infrarenal (n = 8). All patients had extensive collateral vascular supply to the
      lower extremities with absent (n = 7) or mild (n = 6) claudication. Surgical
      renal revascularization was achieved with hepatorenal bypass (n = 6),
      mesenterorenal bypass (n = 4), or splenorenal bypass (n = 3). None of the
      patients underwent concomitant aortic replacement. There were no operative
      deaths. Postoperatively, hypertension was improved in 10 patients, unchanged in 2
      patients, and worse in 1 patient. Renal function was improved in 8 patients,
      stable in 2 patients, and worse in 3 patients. After surgical renal
      revascularization, no patient required aortic replacement, while 1 patient
      underwent extra-anatomic revascularization of the lower extremities. We conclude
      that some patients with renal artery stenosis and abdominal aortic occlusion can
      be managed by surgical renal revascularization alone without a more extensive and
      potentially hazardous aortic replacement. In these patients, extra-anatomic
      techniques can allow safe and successful surgical renal revascularization while
      avoiding surgery on the diseased aorta.

PMID- 8256396
TI  - Urachal cancer: role of conservative surgery.
AB  - Urachal carcinoma is a rare neoplasm (0.22% of all bladder cancers) associated
      with a dismal prognosis. The obscure anatomic position of the tumor often
      minimizes early symptoms and precludes a timely diagnosis. The reported survival
      for urachal neoplasms has been inauspicious, and radical surgery (en bloc
      cystoprostatectomy and wide excision of the urachus and umbilicus) has been
      recommended as the primary treatment. To provide a rationale for the surgical
      management of this cancer, 38 patients with urachal carcinoma were reviewed,
      including 28 men and 10 women (2.8:1) (median age at diagnosis, 56 years; range,
      28 to 88 years). The majority of the tumors were of high grade and stage at the
      time of diagnosis; they were exclusively DNA aneuploid in the 10 patients
      studied. Most patients had partial (segmental) cystectomy/umbilectomy (n = 30) or
      en bloc radical cystoprostatectomy/umbilectomy (n = 4) as their initial
      treatment; five-year overall survival of 43 percent and 50 percent revealed
      essentially comparable outcomes for the two surgical approaches. Thus, in the
      initial management of urachal carcinoma, umbilectomy with partial cystectomy may
      be considered in selected cases; this can enhance quality of life without
      necessarily influencing survival adversely. Rather, disease outcome seems more
      dependent on the adverse biologic potential of this usually DNA aneuploid tumor,
      necessitating the development of more innovative systemic treatment modalities.

PMID- 8256397
TI  - Transrectal ultrasound urodynamics.
AB  - Seventy-seven male patients (34 with cervical spine injury, 32 with thoracic
      spine injury, 9 with lumbosacral spine injury, and 2 with multiple sclerosis) who
      were referred to our spinal cord injury unit for urologic evaluation had
      videourodynamic studies using transrectal ultrasound and fluoroscopy. All were
      studied twice in the same session: first with transrectal ultrasound urodynamics
      (TRUSU) and the second time with conventional fluoroscopic videourodynamics
      (VUD). The findings were compared. Efficacy of TRUSU: (1) clearly documented flow
      of fluid through bladder neck into posterior urethra before clinical leakage
      occurred per urethra; (2) allowed accurate placement of EMG needle electrodes in
      external urinary sphincter under visual guidance; (3) provided high-quality
      imaging of surrounding structures and allowed assessment of bladder neck,
      prostate, seminal vesicles, and posterior urethra; (4) eliminated radiation
      exposure to the patient and the examiner, with no time limit imposed on imaging
      so that repeat studies could be done to evaluate patients on new drug treatments
      or postoperatively at no increased risks; and (5) its availability to most
      urologists at their office at considerably less cost to set up than fluoroscopy.
      In our study TRUSU identified a hypoechoic lesion in the prostate of 1 patient
      and a tumor in the bladder neck of another patient. Fluoroscopic VUD identified 6
      patients with bladder diverticula and 2 with grades 1 and 2 vesicoureteral reflux
      which TRUSU did not identify. Our experience indicates TRUSU is a valid and
      preferable alternative to fluoroscopic VUD for patients with spinal cord injury.

PMID- 8256398
TI  - Effect of repeated instillation of interstitial cystitis urine on the rabbit
      urinary bladder.
AB  - One theory for the etiology of interstitial cystitis (IC) proposes toxic
      substances in the urine. This hypothesis was tested in our laboratory by infusing
      urine into the bladders of rabbits twice weekly for six weeks. For the first
      study rabbits were treated by one-hour biweekly intravesical exposure to urine
      from a symptomatic interstitial cystitis patient, a normal volunteer, or
      physiologic saline. For the second study, animals were exposed to both a high and
      a low molecular weight fraction of urine pooled from 7 interstitial cystitis
      patients, 7 normal female volunteers, and physiologic saline. At the end of six
      weeks the animals were cystoscoped and the bladder was removed the following day
      for histologic and contractile studies. Post-distention glomerulations were
      observed in 3 of the 4 whole IC urine-treated animals and an ulcer identical to
      the classic "Hunner's ulcer" was seen in one of these animals. Post-distention
      petechial hemorrhages were also noted in all 5 of the high molecular weight IC
      urine-treated animals but in none of the others, suggesting a difference between
      IC and normal urine. These IC urine-treated groups also showed the greatest
      degree of histologic changes including edema and plasma cell infiltrates in the
      lamina propria, submucosa and perivascular tissue. However, there was no
      statistically significant difference in bladder capacity, micturition patterns,
      or contractile response of bladder strips. These results indicate that there are
      substances with nominal molecular weight greater than 10 kD in interstitial
      cystitis urine that induce changes in the rabbit bladder that resemble bladders
      of interstitial cystitis patients.

PMID- 8256399
TI  - Personality variables involved in chronic prostatitis.
AB  - Psychologic factors have been considered to play an important role in the
      etiology of chronic prostatitis. Earlier studies are often based on a
      psychoanalytical perspective and seldomly used quantitative approaches. In the
      present study quantitative tests are used to investigate personality variables
      which are suggested in the literature as underlying chronic prostatitis. A group
      of 50 chronic prostatitis patients was compared with a group of 50 patients seen
      for a vasectomy. Psychologic measures were taken by means of a personality
      inventory (NVM, Dutch short form of the MMPI), a symptom checklist (SLC-90), and
      a depression inventory (IDD). Results showed statistically significant
      differences between the groups, with the chronic prostatitis patients scoring
      consistently higher on the measures than vasectomy patients. However, these
      differences in scores were not of a great magnitude and minor compared with
      differences in scores from psychiatric patients. Discriminant analysis suggested
      somatization and depression to be the key variables to distinguish chronic
      prostatitis patients from vasectomy patients. Overall, it seemed unfounded to
      label chronic prostatitis patients "neurotic" or "psychopathologic," and it was
      impossible to conclude that there are personality variables that specifically
      identify the chronic prostatitis patients.

PMID- 8256400
TI  - Comparison of ultrasound-guided and digitally directed transrectal biopsy of
      palpable prostate lesions.
AB  - The role of ultrasound in the diagnosis of prostate cancer is still evolving. We
      used ultrasound to examine 202 patients with palpably abnormal prostates. Of 151
      patients undergoing biopsy, ultrasound-guided biopsy was comparable to digitally
      directed biopsies in cancer detection (92% vs 90.7%). The two methods are
      complementary and should both be considered in patients with palpably abnormal
      prostates.

PMID- 8256401
TI  - Selection of patients for laparoscopic pelvic lymphadenectomy prior to radical
      prostatectomy: a decision analysis.
AB  - Indications for laparoscopic pelvic lymphadenectomy prior to radical
      prostatectomy have not been established. Criteria to predict lymph node
      metastases were derived from the preoperative evaluations of 164 prostate cancer
      patients undergoing pelvic lymphadenectomy. Decision analysis was used to
      determine which criteria would be optimal indicators for laparoscopic pelvic
      lymphadenectomy prior to intended radical prostatectomy. Besides a digital rectal
      examination suggesting uncontained tumor, which was the best indication for
      laparoscopic pelvic lymphadenectomy, the most useful criteria were sonographic
      tumor volume > or = 3 cc and prostate-specific antigen (PSA) > or = 20 ng/mL. If
      either parameter was met, the sensitivity for identifying patients with pelvic
      lymph node metastases was 88 percent and the positive predictive value was 42
      percent. When both were met, the sensitivity fell to 47 percent but the positive
      predictive value increased to 67 percent. A combination of Gleason biopsy score
      and PSA was the best criterion that was independent of transrectal
      ultrasonography. Using a PSA > or = 15 ng/mL for tumors with Gleason biopsy score
      > or = 7 or a PSA > or = 25 ng/mL for tumors with a Gleason biopsy score of 5-6
      had a sensitivity of 71 percent and positive predictive value of 48 percent for
      identifying patients with pelvic lymph node metastases. In selecting patients for
      laparoscopic pelvic lymphadenectomy prior to radical retropubic prostatectomy,
      criteria with a positive predictive value greater than 39 percent maximize the
      utility of laparoscopic pelvic lymphadenectomy. Prior to radical perineal
      prostatectomy, laparoscopic pelvic lymphadenectomy will identify pelvic lymph
      node metastases that would otherwise be undetected by prostatectomy alone. The
      sensitivity of selection criteria, therefore, should be increased, as long as the
      positive predictive value remains above 20 percent.

PMID- 8256402
TI  - Effect of multidose intracorporeal injection and audiovisual sexual stimulation
      in vasculogenic impotence.
AB  - Erections are inhibited by sympathetic stimulation. Anxiety or psychologic
      inhibition may produce abnormal response during impotence workup. The use of
      intracorporeal alpha blockers (phentolamine) and audiovisual sexual stimulation
      (AVSS) has been used to decrease sympathetic outflow and enhance erectile
      response. Thirty-three patients with suspected vasculogenic impotence were
      studied. They underwent pulsed Doppler ultrasound (PDUS) with multiple doses of
      tri-mix (mix of papaverine, phentolamine, and prostaglandin E1). AVSS was applied
      after maximal response to tri-mix. Seventeen patients (51.5%) responded to
      multidose with grade IV or V erection. When AVSS was started, 5 more patients
      responded, and 7 upgraded to grade V with overall response of 40 percent. AVSS
      can augment the in-office response to pharmacologic testing above that obtained
      by "maximal" pharmacologic dosing, thereby increasing the sensitivity and
      specificity of the test.

PMID- 8256403
TI  - Relationship between contraction and relaxation in human and rabbit corpus
      cavernosum.
AB  - Although alterations in corporeal smooth muscle tone undoubtedly play an
      important role in the etiology of erectile dysfunction, the relationship between
      the degree of corporeal smooth muscle contraction and the magnitude of the
      observed relaxation response has never been quantitated. Thus, in vitro studies
      were conducted to examine the relationship between alpha 1-adrenergic
      contractility, and relaxations elicited by the clinically and physiologically
      relevant vasorelaxants, nitroglycerin, nitroprusside, and prostaglandin E1.
      Corporeal tissues strips were isolated from impotent and potent men, as well as
      sexually mature rabbits, and precontracted over a wide range of phenylephrine
      doses, prior to exposure of each tissue to the same dose of vasorelaxant. Plots
      of percent contraction versus percent relaxation revealed that the relationship
      between contraction and relaxation was accurately described by a first order
      linear equation, and characterized by an inverse relationship in all tissues
      studied, for all vasorelaxants examined. Statistical analysis indicated that the
      slope of the regression line was significantly greater than unity in all
      corporeal tissues obtained from patients with organic impotence; however,
      corporeal tissues obtained from patients with documented erections and from
      sexually mature rabbits had significantly lower slopes that were
      indistinguishable from unity. The existence of an inverse relationship between
      contraction and relaxation, even in the absence of organic disease, emphasizes
      the importance of the level of basal corporeal smooth muscle tone per se. These
      studies provide further evidence implicating heightened adrenergic tone as a
      significant etiologic factor in erectile dysfunction.

PMID- 8256404
TI  - Ureteral reimplantation: postoperative management without catheters.
AB  - We reviewed the medical records of 34 consecutive children with reflux who
      underwent simple ureteroneocystostomy at our institution and an affiliated
      hospital between 1991 and 1992. Fourteen patients were managed with ureteral and
      urethral catheters during the initial postoperative period, and 20 patients were
      managed with a "catheterless" technique employing neither of these devices. The
      latter group had a 50 percent decrease in length of hospital stay with 20 percent
      decrease in hospital costs when compared with the former. They also seemed to
      have less postoperative discomfort as evidenced by a 50 percent decrease in
      administered pain medicine. Complete follow-up was obtained in all cases, and
      there were no complications or failures.

PMID- 8256405
TI  - Congenital penile curvature (chordee without hypospadias).
AB  - We treated 30 patients aged six months to nine years with congenital penile
      curvature from 1988 to 1993. Twenty-four patients appeared to have a primary
      curvature with normal corpus spongiosum. In 12 of these 24 patients dissecting
      skin and dartos fascia were adequate to straighten the penis. In the other 12
      patients, artificial erection demonstrated a varied degree of convexity of the
      penis after the skin and dartos fascia release, implying a disproportion of the
      corpora cavernosa bodies. We corrected this deformity using dorsal tumica
      albuginea plications (TAP). The remaining 6 patients presented with a primary
      curvature and hypoplastic urethra. In 5 of these patients we divided the
      hypoplastic midportion of the urethra leaving the meatus naturally on the glans
      and replaced the midurethral segment using a tubularized island flap. Of these 5
      patients 2 required TAP for penile straightening. The final patient with a
      hypoplastic urethra was managed by preserving the urethral plate and applying an
      only island flap urethroplasty. Complications were one fistula and two mild
      ventral penile curvatures, presently not severe enough for reoperation (mean
      follow-up 2.6 years). We present a systematic approach for the repair of
      congenital penile curvature using intraoperative artificial erection, TAP, and
      the island flap urethroplasty when needed.

PMID- 8256406
TI  - New technique for repair of rectal injury.
AB  - Injury to the rectum is a potentially serious complication of pelvic surgery. The
      management of rectal injury is controversial. We present a technique of using
      flaps of endopelvic fascia to reinforce the repair and isolate the injury site.
      We have utilized this approach in 4 men undergoing retropubic prostatectomy
      without complications.

PMID- 8256407
TI  - Operative management of adrenal metastases from lung carcinoma.
AB  - Most surgeons consider patients with solitary adrenal metastasis from a primary
      lung carcinoma incurable and avoid excision of both the adrenal and primary lung
      tumors. However, several cases of successful surgical management of these
      patients recently have been reported. We reviewed 12 surgically treated patients
      with isolated adrenal and lung disease and identified 2 survivors of greater than
      fifteen years (17%) and 4 additional patients who are still alive following
      combined resection (34%). This survival rate, albeit in a selected population,
      represents an improvement over the natural history of nine months' survival. We
      suggest that if after six to twelve months of following patients with lung cancer
      and isolated adrenal metastasis no other evidence of spread of disease is
      evident, the tumor biology may be favorable and resection of both adrenal and
      lung lesions is reasonable.

PMID- 8256408
TI  - Missile injury of upper ureter treated by delayed renal autotransplantation and
      ureteropyelostomy.
AB  - We report a case of extensive upper ureteral loss due to a missile injury managed
      by delayed renal autotransplantation and ureteropyelostomy using the residual
      lower ureteral segment. The successful outcome attests to the value of this
      therapeutic strategy in severe traumatic injuries to the ureter secondary to
      bullet or shrapnel fragments.

PMID- 8256409
TI  - Active chemotherapy for metastatic stromal cell tumor of the testis.
AB  - Metastatic stromal cell tumors of the testis are largely refractory to
      chemotherapy. We report a case of a young man with widely metastatic testicular
      stromal cell tumor who achieved complete clinical remission following
      chemotherapy with etoposide, ifosfamide, cisplatin, and bleomycin.

PMID- 8256410
TI  - Sonographic demonstration of calculi within a urethral diverticulum.
AB  - A case in which sonography demonstrated that calculi may arise in female urethral
      diverticula is presented. The diagnosis of female urethral diverticula is
      reviewed.

PMID- 8256411
TI  - Reservoir characteristics of Mainz pouch studied in animal model. Osmolality of
      filling solution and effect of oxybutynin.
AB  - In a canine model of the Mainz pouch, intracavitary pressure and compliance were
      measured during instillation of isosmotic and hyperosmotic (900 mmol/kg water)
      solutions of saline. Wall properties of small- and large-bowel segments of the
      pouch were assessed individually by sonomicrometry. Intraluminal pressures
      increased more steeply during filling with hyperosmotic solution, resulting in
      reduced distensibility of small- and large-bowel segments. Additionally,
      instillation of the hyperosmotic solution resulted in increased amplitudes and
      frequency of intracavitary pressure waves. The results indicate that this was the
      result of a combination of intensified bowel contractions and an increased mural
      tension. Topical application of oxybutynin abolished these effects. These
      findings are reviewed in light of the nocturnal increase in urine osmolality, its
      correlation with nocturnal incontinence in patients with enterocystoplasty, and
      possible treatment choices.

PMID- 8256412
TI  - Effects of pregnancy on urethral and bladder neck function.
AB  - Pregnancy and menopause induce morphologic as well as functional changes in the
      female urethra. Symptoms of bladder irritation (frequency, urgency) and
      incontinence are frequent findings in these conditions and are considered to be
      due to alterations in the distribution of autonomic receptors induced by the
      changes in the hormonal milieu. In the present study, the functional responses to
      field stimulation (FS) and autonomic agonists of the bladder neck and urethra of
      pregnant, and virgin New Zealand White rabbits were compared using isolated
      muscle strips. Passive length-tension studies demonstrated a significantly
      greater compliance of strips (bladder neck and urethra) from pregnant rabbits
      than from virgin rabbits. FS elicited frequency dependent contractile responses
      in all strips. Phentolamine was significantly more effective at inhibiting the
      field stimulated contractile response of urethral strips from pregnant than from
      virgin rabbits. Atropine was significantly more effective at inhibiting the
      response to FS of strips isolated from bladder necks of virgin rabbits than in
      strips isolated from pregnant rabbits. Atropine was significantly less effective
      at inhibiting the response to FS of strips isolated from urethras of pregnant
      rabbits than of strips from virgin rabbits. Strips of bladder neck and urethra
      isolated from virgin rabbits responded with significantly greater contraction to
      phenylephrine than strips isolated from pregnant rabbits. The magnitude of field
      stimulated relaxation was significantly greater in urethral strips than in
      bladder neck strips, and also greater in urethral strips isolated from virgin
      rabbits than in strips isolated from pregnant rabbits. In conclusion, pregnancy
      induces profound hormonal changes which, in turn, result in the alteration of the
      compliance and functional responses of the bladder neck and urethra to various
      forms of autonomic stimulation and relaxation.

PMID- 8256413
TI  - [Increasing criminal insurance fraud is only partly detected by the law].

PMID- 8256414
TI  - [Amputation of fingers or a hand. Accident or self-mutilation].
AB  - Among the high number of cases of hand injuries investigated each year by
      accident insurance companies, cases continually occur which give rise to the
      suspicion of attempted insurance fraud by means of purposely inflicted injuries.
      Such cases are often difficult to prove. Based on 3 case reports (amputation by
      means of a chain saw, a blow with an axe and a cutting machine), reconstruction
      at the place of the crime is shown to be extremely advantageous. The
      reconstruction of the crime is one of the most important evidential elements. It
      is recommended for all cases where there is any doubt.

PMID- 8256415
TI  - [Comments on simulation and experts. A contribution from forensic practice].
AB  - The report deals with an insurant (private accident and health insurance), who
      succeeded in deceiving the university hospital of his mothertown for a long time
      and in a cost intensive way after he had an alleged concussion followed by an
      extreme, consecutive decline of his ability to see. The malingerer finally
      processed some documents, which forced the person inchange in case of a high
      percentage of disability to pay a sum insured of about one million DM or more. In
      the practice of an expert it was possible to find him guilty in a simple and
      cheap way.

PMID- 8256416
TI  - [Driver's license and diabetes. Legal and social medicine aspects].
AB  - The diagnosis of diabetes mellitus is accompanied by a lot of personal and social
      consequences for the patient himself. One of the most important problems is the
      influence of the disease on the patients driving skills. This aspect is discussed
      according to the recommendations of the German ministry of traffic, and advice is
      given for the diabetic patient taking part at the daily traffic as a car driver.

PMID- 8256417
TI  - [Incomplete clinical inquiry and documentation of findings as the cause of legal
      problems after accidental injuries].
AB  - The starting point of every expert opinion is the clinical inquiry and the
      description of clinical findings based on a sorrow and complete examination.
      Without this it can be difficult or even impossible for the expert to answer with
      sufficient safety the relevant question concerning the sequelae of an accident,
      or concerning the causal connection between trauma and damage or, as well,
      concerning possible medical malpractice. Based on 238 expert opinions given by
      the author within two years, it becomes obvious, that in 18% (41 cases) the
      opinion ended in an unsatisfactory manner, exclusively for incomplete description
      of (clinical) findings. This was on one hand because the specific question to the
      expert could not be answered in a sufficient and safe way, or, on the other hand,
      because the incomplete inquiry was the very reason for a legal dispute.

PMID- 8256418
TI  - [The significance of imaging procedures for expert assessment of tendon and
      meniscus ruptures].
AB  - Degenerative soft tissue lesions could be proved witherto only histologically-
      supposed biopsy was carried out early and sufficiently. This is rarely done.
      Morphologic changes can be demonstrated by sonographic and MRI investigation at
      any time, in any region other than the lesion and especially on the contralateral
      side for comparison. The visualisation of degenerative changes, fresh and old
      ruptures of soft tissue and scarifications has a striking evidence even for
      medical laymen and allows--contrary to histologic examination--diagnostic
      assessment in time. Thus misinterpretations by physician, patient and insurance
      company can be avoided. The phasical development of soft tissue disease
      (necrobiosis, degeneration, defect, reparation) can be demonstrated and related
      to conventional x-ray findings. The visualisation of a chronological process
      emphasizes the importance of the patient's history, clinical and x-ray signs and
      thus improves diagnostic accuracy by combination of all diagnostic means. The
      false negative result of conventional x-rays can be avoided as well as the
      misinterpretation or simplification of complex medical legal problems.

PMID- 8256419
TI  - [Eponyms of distal radius fractures. Colles-Pouteau, Smith-Goyrand and Barton
      fractures and their importance in the trauma surgery patient sample].
AB  - Fractures at the distal end of the radius are quite common. So, these fractures
      are well known to represent consequences of industrial accidents leading to
      temporary unfitness for work, too. Eponym descriptions of fractures may mislead
      authors and readers as well if used in a non-uniform way in medical literature.
      Using the original articles of the first describing authors a clear distinction
      of eponyms concerning fractures near to the wrist joint is given. The authors of
      this feature report of the clinical experience in treatment and results of distal
      radius fractures in combination with aspects of expert opinions on these
      fractures.

PMID- 8256420
TI  - [Dislocation injury of the cervical spine. Which factors are responsible for
      persistence of complaints?--A study of 112 patients in expert assessment].
AB  - A retrospective study of 112 patients reveals that persisting symptoms are
      frequently found in the victims of car accidents and in combination with
      psychogenic factors. As far as insurance claims are concerned, we suggest
      orthopedic and neurologic analysis at an early stage.

PMID- 8256421
TI  - Spongiform encephalopathy in a herd of greater kudu (Tragelaphus strepsiceros):
      epidemiological observations.
AB  - A small herd of greater kudu, derived from three individuals, has been maintained
      at the Zoological Society of London since 1970. Spongiform encephalopathy has
      been diagnosed in five out of eight of the animals born in this herd since 1987.
      With the possible exception of the first confirmed case, none of these is thought
      to have been exposed to feeds containing ruminant-derived protein. The pattern of
      incidence suggests that greater kudu are very susceptible to the disease and that
      natural lateral transmission may have occurred among them.

PMID- 8256422
TI  - An evaluation of the potential effects of ivermectin on the decomposition of
      cattle dung pats.
AB  - The parasiticide ivermectin has been administered to domestic livestock since
      1981 to control internal and external parasites, including insects; some of the
      ivermectin is excreted unchanged in faeces. Concerns over the effects of
      ivermectin on dung-utilising insect populations and the potential for consequent
      persistence of dung on pastures have been raised. This paper presents the results
      of a study over two grazing seasons of the rate of decomposition of cattle dung
      pats exposed to normal environmental influences. The cattle had been treated at
      therapeutic levels with either an injectable or a sustained release bolus
      formulation of ivermectin. It was concluded that the rate of decomposition of the
      dung pats, the extent of their avoidance by the cows, the organic matter content
      of the soil and the populations of earthworms in the pastures were not affected
      by the use of ivermectin.

PMID- 8256423
TI  - Bovine abortion associated with Yersinia pseudotuberculosis.

PMID- 8256424
TI  - Clinical efficacy of injectable amoxycillin against furunculosis in Atlantic
      salmon broodstock.

PMID- 8256425
TI  - Warbles survey of British cattle.

PMID- 8256426
TI  - Bovine Neospora caninum abortion in the UK.

PMID- 8256427
TI  - Persistent infection with Streptococcus equi and the epidemiology of strangles.

PMID- 8256428
TI  - PCR-based detection of CEM agent.

PMID- 8256429
TI  - Isolation and characterization of gamma delta T lymphocyte cell lines from
      Sinclair swine peripheral blood.
AB  - Sinclair miniature swine represent a breed of miniature swine which display a
      significant incidence of inheritable melanoma which undergo a developmentally
      regulated spontaneous regression. In an attempt to characterize the host cellular
      immune response to the melanoma, lymphocyte cell lines have been generated from
      peripheral blood and designated as peripheral blood lymphocyte cell lines
      (PBLCLs). The cell lines were expanded in vitro without the addition of exogenous
      mediators, cloned by limiting dilution, and characterized by flow
      microfluorimetry, Western, and Northern blot analysis. The cell lines were shown
      to be CD2-, CD4-, CD8-, and slg-, a phenotype consistent with a null cell
      population described in swine. The null cell population in swine has been
      reported to consist of a subpopulation of cells which express the gamma delta T
      cell receptor (TCR) heterodimer, swine gamma delta T lymphocytes. The PBLCLs were
      further analyzed by flow microfluorimetry and observed to express the IL-2R,
      swine MHC Class II antigens, and the endothelial lymphocyte adhesion marker
      (CD44), which can function as a homing receptor for the skin. In addition, the
      PBLCLs were observed to express the antigen which is recognized by mAb 86D, an
      antibody that has been reported to recognize an external epitope on a subset of
      gamma delta TCR bearing swine T lymphocytes. Western blot analysis of Triton X
      114 phase fractions of a PBLCL revealed a protein recognized by the W6 antibody,
      an antibody which recognizes a conserved region of the C delta chain.
      Furthermore, Southern and Northern blot analysis indicated that the PBLCL have
      rearranged the TCR gamma chain gene and express mRNA from the TCR gamma and delta
      chain genes prior to and following treatment with ionomycin or Concanavalin A.
      Therefore, the data indicates that the PBLCLs represent swine gamma delta T
      lymphocyte cell lines which should enable us to enhance our understanding of the
      role of gamma delta T lymphocytes in the porcine immune system.

PMID- 8256430
TI  - Concentrations of passively acquired IgG1 antibodies in the intestinal lumen of
      the neonatal calf.
AB  - Passively acquired specific antibodies in the intestinal lumen are thought to
      provide protective immunity against infections with rotaviruses and other
      enteropathogens. In this study, concentrations of functional antibody in the
      intestinal lumen derived from diet and circulation were measured using 2,4
      dinitrophenol (DNP) specific antibody of the IgG1 isotype, radiolabelled with
      125I. The labelled IgG1 antibody was administered to neonatal calves either
      orally in the daily milk diet for three consecutive days (Group 1), or by a
      single intravenous injection (Group 2). After equilibration, the concentrations
      of protein-bound 125I and the specific DNP binding activities of the labelled
      protein in the intestinal lumen were measured, and intestinal concentrations of
      functional IgG1 were estimated. In Group 1 calves, protein bound 125I
      concentrations in the pooled small intestinal contents at 2 and 12 h after a milk
      meal were 50.8 +/- 20.5% and 7.9 +/- 3.4%, respectively, of the milk
      concentration. Protein bound 125I concentrations in the small intestinal contents
      were 0.7 +/- 0.4% (mean +/- SD) of serum concentrations of Group 2 calves, and
      were similar at 2 and 12 h after a milk meal. For a calf with average serum
      passive IgG1 concentrations drinking milk with normal IgG1 content, these results
      predict IgG1 concentrations in the small intestinal contents of milk fed calves
      at 2 h after a milk meal to be 0.6 mg ml-1, half of which originates from the
      milk and half from the circulation. At 12 h after a milk meal, intestinal IgG1
      concentrations fall to approximately 0.3 mg ml-1, most of which originates from
      the circulation. Antibody in the intestinal lumen originating from serum retained
      more antigen (DNP) binding affinity than that ingested in the milk diet.
      Therefore, both dietary and circulating IgG1 contribute significantly to passive
      IgG1 antibody concentrations in the small intestinal lumen of neonatal calves,
      but milk derived IgG1 antibody concentrations in the small intestinal lumen were
      not maintained between twice daily feedings.

PMID- 8256431
TI  - Inhibition of bovine mononuclear cell proliferation, interleukin-2 synthesis,
      protein-tyrosine kinase and leukotriene B4 production by a protein-tyrosine
      kinase inhibitor, genistein.
AB  - Genistein, an isoflavanoid compound, a selective inhibitor of protein-tyrosine
      kinase (PTK), inhibited PHA-stimulated bovine peripheral blood mononuclear cell
      proliferation (PBMC), interleukin-2 (IL-2) production, phosphorylation of PTK
      p56lck. Further, genistein also inhibited leukotriene B4 production from A-23187
      stimulated cultures. Our data suggest that the PTK plays an important role in the
      signal transduction of bovine PBMC proliferation.

PMID- 8256432
TI  - Immunocytochemical and immunoelectron microscopy study of dendritic cells in the
      caecal tonsils of chickens infected with Eimeria tenella.
AB  - In the present study S-100 protein containing cells in the caecal tonsil were
      investigated, both at light microscopic and at electron microscopic levels, after
      oral coccidia inoculation (Eimeria tenella). The birds were infected with a
      single (Day 0) or two (Days 0 and 21) infective doses of 500 oocysts.
      Immunoelectron reactivity for S-100 protein was demonstrated in infected
      chickens, but not in controls. It was found in follicular dendritic cells and
      interdigitating dendritic cells which were present in the germinal center and
      diffuse lymphoid tissue respectively, both of them being located in the deep
      lymphoid tissue near the muscular layer and around the deep glands. Outside the
      lymphoid tissue, immunoreactivity for S-100 protein was found in cells lying
      between the epithelial cells of the deep crypt epithelium. Positivity for S-100
      protein was observed at 3, 12, 18, 24 and 48 h after the first inoculation as
      well as on Days 3, 5, 6, 7, 8, 25 and 30 of the experiment. Positive reaction for
      S-100 protein was detected both while schizont (the more immunogenic stage)
      development occurs and the number of sporozoites in the caeca lumen was higher,
      as well as when the production of oocysts reached a maximum. Complementary
      studies demonstrated that S-100 positive dendritic cells gave a negative reaction
      for esterase activity, whereas a subset of S-100 negative intraepithelial
      lymphocytes located between epithelial cells lining the deep glands exhibited
      esterase activity. These esterase positive cells are hypothesized to be involved
      in the regulation of local defences.

PMID- 8256433
TI  - Purification and characterization of equine complement factor C3.
AB  - A rapid method for purifying equine C3 which yields milligram quantities of pure
      C3 is described. Protein from equine plasma was selectively precipitated with
      polyethylene glycol, and the C3 was purified by anionic and cationic exchange
      HPLC. The yield from this procedure was 12%. The purified C3 was composed of an
      alpha chain (118 kD) and a beta chain (68 kD) linked by at least one disulfide
      bond, and it had an isoelectric point of 4.7. Amino acid analysis indicated a
      strong conservation of amino acid usage between equine and human C3. The N
      terminal sequences of the alpha and beta chains were homologous to human, mouse,
      and rat C3, and activation of C3 produced breakdown products similar in molecular
      weight to C3b and iC3b of other species. Equine C3 appeared to be functionally
      dependent upon a reactive thiolester as treatment of fresh equine serum with
      methylamine abrogated its hemolytic activity.

PMID- 8256434
TI  - A non-hemolytic assay for the activation of the alternative pathway of bovine
      complement.
AB  - An assay for assessing activation of the bovine alternative pathway of complement
      was developed. The assay focused on events on the surface of yeast. Yeast cells
      were incubated with EGTA-Mg2+ plasma, washed and the yeast-bound complement
      proteins eluted by 100 mM methylamine. Detection of eluted proteins was achieved
      by Western blot and ELISA. An ELISA for the quantification of the Bb fragment of
      factor B was chosen to measure activation of the alternative pathway of
      complement. Using this system, it was possible to demonstrate the kinetics of
      deposition of Bb on yeast incubated with plasma samples from individual cattle
      and to show differences between cattle. We were able to categorize cattle into
      'fast or slow amplifiers' of the alternative pathway of complement. We suggest
      that this classification has implications for host protection against invading
      microorganisms.

PMID- 8256435
TI  - Immune lysis of Trypanosoma congolense: generation of a soluble covalent complex
      of variant surface glycoprotein and bovine complement component C3b.
AB  - Organisms of Trypanosoma congolense variant antigenic type TC13 (VAT TC13) were
      incubated, at 37 degrees C for 60 min, with fresh bovine serum in the presence of
      antibody specific for the variant surface glycoprotein (VSG). Upon immune lysis,
      soluble VSG (54 kDa) and a larger complex (about 225 kDa), containing VSG, was
      detected in the supernatant fluid of the mixture. Neither soluble VSG nor the VSG
      complex were detected when fresh bovine serum was incubated with organisms of T.
      congolense in the absence of specific antibody. Within a narrow range of low
      antibody concentration, the release of soluble VSG and the formation of the VSG
      complex were correlated with the amount of specific antibody added to the
      mixture. The VSG complex could be precipitated with rabbit antibodies specific
      for VSG of VAT TC13 or antibodies specific for bovine complement C3. The VSG
      complex was detected by Western blot with rabbit anti-VSG of VAT TC13 as well as
      rabbit antibovine C3. The complex was found to consist of VSG covalently bound to
      bovine complement component C3b. Potential pathophysiological implications are
      discussed.

PMID- 8256436
TI  - A study on the engraftment and trafficking of bovine peripheral blood leukocytes
      in severe combined immunodeficient mice.
AB  - Bovine lymphoid cells were engrafted into untreated and into sublethally
      irradiated scid/scid mice, following intraperitoneal (i.p.) injection of bovine
      peripheral blood leukocytes (PBL). To distinguish bovine from murine cells,
      bovine PBL were stained prior to i.p. injection with a fluorescent cell linker
      compound, PKH26-GL and, after cell recovery, labelled with a monoclonal antibody
      (mAb) reactive with the bovine pan leukocyte cell surface marker, CD45, and
      analyzed by flow cytometry. This dual labelling system was used to monitor tissue
      localization and migration of bovine cells within PBL-SCID-bo from 30 min to 64
      days after bovine PBL injection. Inoculated bovine PBL were rapidly cleared from
      the peritoneal cavity of PBL-SCID-bo over the first 24 h after injection, then
      bovine cell numbers within the peritoneal cavity increased gradually over the
      next 35 days. No bovine cells were observed in the peritoneal wash from either
      non-irradiated or irradiated mice after Day 56. Bovine cells were detected in the
      spleens of both non-irradiated and irradiated mice 12-14 days after inoculation,
      but were undetectable in non-irradiated and irradiated mice after Day 56, and in
      irradiated mice after Day 35. This decrease coincided with a significant
      reduction in both the numbers of bovine cells in the peritoneal cavity, and in
      the levels of bovine Ig detected in the sera. Bovine IgG and bovine IgM were
      detected in both normal and irradiated PBL-SCID-bo by 4 days after PBL injection,
      and remained detectable to 8 weeks after inoculation. T-cells appeared to be the
      predominant bovine cell population in the spleens. In a small proportion of both
      normal and irradiated PBL-SCID-bo, spleens three to 20 times the size of a normal
      SCID mouse spleen were observed. Relatively high levels of bovine cells were
      detected in the thymuses of some irradiated PBL-SCID-bo. Sporadic, low levels of
      bovine cells were observed in the mesenteric lymph nodes, peripheral blood, and
      kidneys of normal and irradiated mice, and in the lungs and livers of non
      irradiated but not irradiated PBL-SCID-bo. Sublethal gamma irradiation of SCID
      recipients appeared to enhance engraftment of bovine cells into the murine spleen
      and thymus.

PMID- 8256437
TI  - In vitro and in vivo canine mononuclear cell production of tumor necrosis factor
      induced by muramyl peptides and lipopolysaccharide.
AB  - Tumor necrosis factor (TNF) is a potent mediator of tumor cell killing by
      activated monocytes and macrophages. We measured TNF activity induced by muramyl
      peptides and lipopolysaccharide (LPS) in normal dogs. Canine adherent mononuclear
      cells were isolated and cultured in either medium alone or medium containing
      muramyl dipeptide (MDP) or MDP plus LPS. After 18 h, culture supernatants were
      collected and assayed for TNF activity. Sera from dogs injected with liposome
      encapsulated muramyl tripeptide-phosphatidylethanolamine (L-MTP-PE) were also
      evaluated for TNF activity. TNF activity both in supernatants and in sera was
      detected in a 18 h WEHI-164 cell cytotoxicity assay and was confirmed by a
      monoclonal antibody directed against recombinant human TNF-alpha. Results showed
      a significant increase in TNF activity from mononuclear cells exposed to MDP or
      MDP plus LPS of 20% and 88%, respectively; P < 0.0005. Serum TNF activity rapidly
      increased within 2-3 h post L-MTP-PE injection and subsequently declined to
      pretreatment level at 4 h post administration. This study demonstrates that MDP
      +/- LPS can stimulate canine adherent mononuclear cells to release TNF and
      intravenous injection of L-MTP-PE is capable of rendering the in vivo release of
      TNF in normal dogs.

PMID- 8256438
TI  - Cloning and expression in mammalian cells of porcine tumor necrosis factor alpha:
      examination of biological properties.
AB  - We have cloned a full length complementary DNA (cDNA) of the porcine tumor
      necrosis factor alpha (pTNF-alpha) gene and expressed it in porcine and murine
      cells. Total RNA obtained from lipopolysaccharide (LPS) stimulated porcine
      peripheral blood mononuclear cells was reverse transcribed with a specific
      antisense pTNF-alpha primer to generate a single stranded cDNA which was
      subsequently amplified by the polymerase chain reaction utilizing an additional
      pTNF-alpha specific sense primer. The resulting double stranded cDNA was
      introduced into the pBMGNeo expression vector and transfected by electroporation
      in porcine (PK(15)) and murine (L929) cell lines. TNF-alpha bioactivity was
      detected in the supernatant of the transfected cells using a standard L929
      bioassay or a PK(15) bioassay. The activity was zinc inducible as expected for a
      gene controlled by a metallothionein promoter. The bioactivity was not lowered by
      an anti-mouse TNF-alpha antiserum neutralizing murine, but not human TNF-alpha
      and a broad immunoreactive band of 17-19 kD was detected using an anti-mouse TNF
      alpha serum suitable for immunoblotting. This newly developed tool will allow us
      to investigate the role of TNF-alpha in pathogenesis of viral infections and gram
      negative sepsis.

PMID- 8256439
TI  - Delayed hypersensitivity testing as a clinical measure of cell-mediated immunity
      in the cat.
AB  - The purposes of this study were to examine the cell-mediated immune response of
      the normal cat to the modified live feline viral rhinitis, calicivirus, and
      parvovirus (FVRCP) vaccine (Felocell CVR, Norden, Lincoln, NE), and to evaluate
      the intradermal skin test as a clinical measure of the immune response of cats.
      Vaccine and diluent were injected intradermally on the dorsal pinna of 34 normal
      adult cats. Skin thickness measurements, lymphocyte counts, and Concanavalin A
      mitogenesis indices were evaluated in 18 of these cats. Skin biopsies were
      obtained in 16 cats. In normal cats, the FVRCP vaccine induced a delayed
      hypersensitivity response characterized by a mononuclear infiltrate most
      pronounced at 72 h. Five cats with either feline leukemia (FeLV) or feline
      immunodeficiency virus (FIV) were tested and had a significantly reduced response
      to the skin test. The skin test provides a clinically useful method of evaluating
      immune function in cats and may be useful in development of a prognostic index.

PMID- 8256440
TI  - [The isolation and identification of a Clostridium botulinum serotype A strain].
AB  - 319 soil specimens were collected from different places of China for isolating
      Clostridium botulinum. A strain of Clostridium botulinum was isolated from a
      culture of soil specimens in Ruoergai of Sichuan Province, the strain was called
      As-3. The As-3 was identified as Clostridium botulinum serotype A according to
      its biological properties, biochemical serological and toxicological
      characteristics and DNA determination. Its DNA G + C mol is 24.9%. The toxin
      produced by As-3 strain can only be neutralized by type A antiserum.

PMID- 8256441
TI  - [The isolation of Vibrio alginolyticus bacteriophage].
AB  - We identified 4 bacteriophages of V. alginolyticus in 29 ones, which were first
      isolated from seafood. According to their character of the plaques, they were
      classified into two kinds: one plaque was clear, the other was opaque. The size
      of these plaques were different and their diameters are 0.5-3.0mm. By electron
      microscopy observation, they could be classified into two kinds; one has a long
      axie and hexagemal head, and a thin-long tail, the other has an equal axie
      hexagenal head and a very short tail, but the edges and corners aren't clear. The
      multiplication valence of the phages attained to 10(8-9) pfu/ml. Total lysis rate
      of 4 bacteriophages was 72.22% to V. alginolyticus. However, the lysis rate of
      single phage was 9.72-44.4%. 4 bacteriophages all had high host specificity.
      Cross-lysis reaction wasn't found in the test of original solution of
      bacteriophages to 612 strains of different genus bacteria and 697 strains of
      genus Vibrio, but they only showed 39% cross-lysis rate to V. parahaemolyticus
      and most part of this phenomenon disappeared at 10 RTD of the phages. Thus, the
      obvious relation of consanguinity was showed between two kinds of bacteria
      strains.

PMID- 8256442
TI  - [Analysis of fatty acid composition of spotted fever group rickettsiae isolated
      in China by gas chromatography].
AB  - In present paper, fatty acid composition of seven Chinese isolates of SFG
      rickettsiae and six prototype strains of SFG rickettsiae were analyzed by GC-MS.
      Tested prototype strains of SFG rickettsiae were R. sibirica (strains 232 and
      246), R. conorii (Simko), R. rickettsi (R), R. akari (Kaplan), R. australis
      (W58); Chinese isolates were An-84, Se-85, W-88 (human strain), MT-84, FT-84 (D.
      nuttalli strain), TO-85 (ova of nuttalli) and Chinese reference strain -JH-74 (D.
      nuttalli). They were propagated in yolk sacs of embryonated hen eggs and purified
      by centrifugation in a 30%-36%-42% discontinuous renografin density gradient. The
      fatty acid composition of selected strains of SFG rickettsiae was analyzed by gas
      chromatography, and then comparison being carried out by single linkage on mini
      computer. Identification of the strains was performed based on the results
      obtained from GC-MS. Results showed that the fatty acid profiles of all the
      isolates from China were quantitatively similar to that of R. sibirica and quite
      different from other prototype strains of SFG rickettsiae.

PMID- 8256443
TI  - [Screening of L-glutamate oxidase forming strains and conditions for enzyme
      production].
AB  - A strain P-26 producing extracellular L-glutamate oxidase was screened out from
      125 Actinomyces. The formation of enzyme was induced by L-glutamate, it reached
      maximum when the microorganism was grown in wheat bran medium containing 0.2% L
      glutamate, 0.5% Na2CO3 and 100% H2O at 28 degrees C for 6 days. The enzyme
      activity could be moderately enhanced by extra supplement of inorganic salts such
      as MgSO4 x 7H2O and CaCl2.

PMID- 8256444
TI  - Anabolic-androgenic steroids.

PMID- 8256445
TI  - [Anabolic-androgenic steroids towards the year 2000].

PMID- 8256446
TI  - History, chemistry and pharmacodynamics of anabolic-androgenic steroids.
AB  - It had been known for centuries that castration resulted in the loss of certain
      secondary male sex characteristics. The first inkling as to the cause of these
      changes were provided in 1849 by a prevention of the regression of the comb and
      wattles of capons by implantation of testis into the abdominal cavity of the
      castrated rooster. The results were correctly interpreted that the testis
      secreted a substance into the blood to regulate the development and maintenance
      of the male characteristics. The first active extract of testis, however, was not
      prepared until 1927. Shortly thereafter (1929), a similar type of activity was
      found in men's urine which was followed (1931) by the isolation of a pure
      substance, androsterone. A substance with the properties of the testis extract
      was quickly (1935) synthesized and proved to be identical to a pure substance,
      testosterone, obtained almost simultaneously from testis extract. Testosterone
      influences the growth, development, and function of practically every organ in
      the body. The chemically and endogenously modified steroids do not have parallel
      effects on the different biological properties of testosterone. Furthermore
      animal species and dose of steroid affect the response of the different organs.
      Many chemically modified steroids and some endogenous steroids of both the C19
      and C21 series exhibit definite separation of undesirable biological effects.

PMID- 8256447
TI  - Anabolic steroids--action on cellular level.
AB  - Although the nature of actions of anabolic steroids is principally that of
      androgens, it still remains difficult to relate the effects observed to specific
      cellular processes and to describe them clearly as related to specific mechanisms
      of action. The dissociation between "anabolic" and "androgenic" actions of a
      steroid can in part be explained by organ specific patterns of steroid
      metabolizing enzymes, which lead to the formation of more or less active
      compounds in different organs. Some actions of anabolic steroids, particularly
      that in skeletal muscle are obviously also mediated by interaction of the parent
      compound or a metabolite with receptors of other steroid classes than androgens,
      e.g. that of glucocorticoids and/or estrogens.

PMID- 8256448
TI  - Pharmacokinetics of anabolic steroids.
AB  - After an anabolic steroid is administered orally there is a rapid increase in its
      concentration in the blood in the following few hours. Excretion of the compound
      and its metabolites takes place via the urine and faeces, usually taking several
      days to completely pass through the system. Parenteral anabolic preparations,
      such as microcrystal suspensions, implants and solutions of nandrolone esters in
      a vegetable oil, are absorbed slowly. The absorption of esters from the site of
      injection is a logarithmic process and depends on the nature of the ester
      concerned. The absorption rate is slower the longer the fatty acid chain in the
      ester. The rate of absorption is important regarding the length of the action,
      and is also relevant for the compound's pharmacodynamic pattern. Metabolism of
      anabolic steroids takes place mainly in the liver and involves reduction,
      hydroxylation and the formation of conjugates. The enzymes that bring about these
      changes and the metabolic pathways involved are similar to endogenous steroids.
      The presence of high concentrations of metabolites in the bile and in the
      intestinal tract points to enterohepatic circulation of metabolites. After the
      administration of slowly-absorbed nandrolone esters the excretion of the
      metabolites continues for weeks or even months. It is probable that the
      absorption rate of the esters from the injection depot is the rate-limiting
      process in the pharmacokinetics of these compounds.

PMID- 8256449
TI  - Metabolic effects of anabolic steroids.
AB  - After 1935 the best method of discovering and measuring the protein-building
      action of androgenic steroids in humans proved to be metabolic balance studies.
      In 1955, when anabolic steroids with less androgens were developed, the nitrogen
      balance method was used again to evaluate and compare the nitrogen-sparing effect
      of the various preparations. The findings of the numerous balance studies that
      were performed are as follows: The injectable 17 beta-esters, such as nandrolone
      phenylpropionate, nandrolone decanoate and methenolone oenanthate exert a strong
      anabolic action for several weeks, amounting to 2-2.50 g nitrogen/day, which
      corresponds to a daily gain of 12-15 g protein or 60-75 g lean body mass. The
      orally active 17-alkyl derivatives induce a dose-dependent nitrogen-saving effect
      of the same order. While the drug is being administered, nitrogen-, calcium- and
      phosphorus-balance studies in osteoporotic patients show calcium and phosphorus
      retention in most cases. Anabolic steroids can abolish a negative nitrogen
      balance brought about by the administration of corticosteroids and anti
      androgens. They thus possess anti-catabolic properties. Nitrogen loss after
      surgical procedures and following accidental traumata can be significantly
      reduced by pre-operative or post-operative treatment with anabolic agents.
      Comparison of the metabolic balance method with isotope studies showed a
      satisfactorily positive correlation. Later calcium metabolism studies in
      osteoporotic patients were mostly performed with various methods such as in vivo
      neutron activation analysis and osteodensitometry. They confirm the calcium
      anabolic effect of certain anabolic steroids.

PMID- 8256450
TI  - Anabolic steroids and total parenteral nutrition.
AB  - Malnutrition develops rapidly with total starvation, especially when a catabolic
      stress is superimposed. The measurement of body composition provides an accurate
      and quantitative measurement of both the nutritional state and the response to
      nutritional therapy. With malnutrition there is a loss of body fat and BCM with a
      concomitant expansion of the ECM. With the appropriate administration of calories
      and amino acid as TPN, a malnourished body composition is restored to normal.
      However the nutritional state is restored relatively slowly, particularly when
      compared to the rapid rate at which malnutrition may develop, especially in the
      septic and starving patient. The administration of nandrolone decanoate, a potent
      anabolic steroid, significantly improves the efficacy of TPN, resulting in a more
      rapid correction of the malnourished state. However, to demonstrate this effect
      an accurate and precise measurement of the nutritional state is required.
      Furthermore it is essential to account for a number of important independent
      variable which influence this response; specifically the caloric intake, the
      nutritional state and the age.

PMID- 8256451
TI  - Anabolic steroids and blood cell production.
AB  - In the past anabolic steroids were the first-choice treatment for pancytopenic
      disorders that were often poorly classified. They are now superseded by other
      more recently developed methods of treatment--for example bone marrow
      transplantation and immunosuppression. This contrasts to the authors' experience,
      and to that of many other haematologists, who have noted anabolic steroid-induced
      responses in patients who were unsuitable for or unresponsive to the new
      treatments. Anabolic steroids did not, however, demonstrate an obvious effect in
      recent controlled trials involving patients with aplastic anaemia. Their use with
      immunosuppressive treatment is currently under investigation. Although anabolic
      steroids rarely reverse the course of anaemia in a myelodysplastic syndrome, even
      a slight haemopoietic improvement is desirable. Children with Fanconi's anaemia
      may benefit from a reduced transfusion requirement. Uraemic patients may
      experience significant side effects on standard erythropoietin (epo) treatment.
      There have been no controlled trials comparing epo versus anabolic steroids or
      epo versus epo in conjunction with anabolic steroids. Data from uncontrolled
      studies indicate a better response to anabolic steroids in children and females
      than in men. In spite of the fact that anabolic steroids have been used for
      almost 30 years, they should be carefully re-evaluated in scientifically
      controlled trials to test their efficacy and to compare them with the new
      treatments. Such trials, however, are impeded by the limited knowledge available
      with regard to pharmacological parameters and optimal treatment schedules.

PMID- 8256452
TI  - Anabolic steroids and fibrinolysis.
AB  - Anabolic steroids increase the activity of the fibrinolytic system by reducing
      plasma levels of inhibitors (plasminogen activator inhibitor type I, histidine
      rich glycoprotein, alpha-2-macroglobulin) and increasing plasma levels of tissue
      type plasminogen activator activity, plasminogen, and plasmin activity (B beta 15
      42 fragment of fibrinogen). Plasminogen activator inhibitor levels are elevated,
      and tissue-type plasminogen activator activity is depressed, in a variety of
      disease states, including premature venous or arterial thrombosis, connective
      tissue disorders, and cancer. Such abnormalities can be reversed by anabolic
      steroids. However the clinical benefits and adverse effects of such treatment
      remain to be established by large, randomized controlled trials.

PMID- 8256453
TI  - The action of anabolic steroids on bone in experimental animals.
AB  - Anabolic steroids are currently used in the treatment of established
      osteoporosis. It has been demonstrated that, at least partly, anabolic steroids
      increase bone density by stimulating bone formation. Very little is known about
      how anabolic steroids affect bone in experimental animals. Because bone studies
      in animals have been performed only with the anabolic steroid nandrolone, or its
      long-acting ester nandrolone decanoate (ND), we present a general overview in
      this paper of the effect of these anabolic agents in various steroid-affected
      animal models for osteoporosis, viz. gonadectomized rats, heparin-treated mice
      and intact or ovariectomized dogs. In rats and mice these agents increase
      longitudinal and periosteal bone growth and bone mass, thus demonstrating their
      anabolic action. They also decrease trabecular bone resorption in ovariectomized
      and orchidectomized rats, which indicates that they have anti-catabolic effects.
      In ovariectomized rats, ND was found to increase the mechanical strength of
      cortical bone, which is an important property in a drug that is intended to be
      used in treating established osteoporosis. In elderly dogs, ND was found to
      stimulate endosteal bone formation. These findings indicate that nandrolone and
      ND have beneficial effects on bone in both oestrogen and androgen-deficient
      animals.

PMID- 8256454
TI  - Epidemiology, biochemistry and some results with treatment of postmenopausal
      osteoporosis.
AB  - The present chapter deals with postmenopausal osteoporosis. This is an important
      disease because it affects millions of people throughout the world. The most
      serious of the osteoporotic fractures, the hip fractures, needs hospitalization,
      causes a high degree of mortality, and results often in dependent people.
      Osteoporosis is thus a significant socioeconomic burden. At the menopause bone
      turnover increases and bone loss accelerates. Postmenopausal bone loss and
      osteoporosis may be prevented by oestrogen replacement therapy, but convincing
      therapy for established osteoporosis does not yet exist. Anabolic steroid therapy
      can, however, increase the bone mineral content a few percentages a year in
      postmenopausal osteoporotic women.

PMID- 8256455
TI  - Anabolic steroids in postmenopausal osteoporosis.
AB  - The anabolic steroids were first developed in the 1950's to provide the anabolic
      advantages of androgens with less androgenic action. They are widely used in the
      treatment of osteoporosis, although their effectiveness has only recently been
      demonstrated with the advent of bone densitometry. It is now established that
      their administration leads to a significant increase in bone mass in osteoporotic
      men and women associated with an apparent conversion of fat into muscle tissue.
      The bone gain is of the order of 3% per annum but the maximal effect is obtained
      in the first few months. The bone gain is probably due to stimulation of bone
      formation and is associated with elevation of serum albumin and fat-free skinfold
      thickness. The most serious side-effect with parenteral use is lowering of voice
      pitch but there is some evidence that oral anabolic steroids may adversely affect
      liver function. The optimum dose and duration of therapy has not yet been
      established.

PMID- 8256456
TI  - Anabolic steroids in corticosteroid-induced osteoporosis.
AB  - Severe osteoporosis represents a major complication of corticosteroid (CST)
      excess. Steroid-induced osteoporosis is characterized by both increased bone
      resorption and inhibition of bone formation. Excessive bone resorption is
      attributed to hyperparathyroidism which is secondary to calcium malabsorption.
      Calcium and vitamin D supplementation or treatment with inhibitors of bone
      resorption are of benefit but they usually lead to further inhibition of bone
      formation. The inhibition of bone formation in CST treated patients is due in
      part to suppression of adrenal androgen secretion. Thus the suppressed
      circulating levels of osteocalcin, a biochemical marker of osteoblast activity,
      in patients on CST can be reverted to normal by administration of anabolic
      steroids. In a prospective controlled trial in patients on long-term CST therapy
      we have observed that nandrolone decanoate therapy, 50 mg intramuscularly every 3
      weeks for 18 months, induces a transient increase in bone mass within the first 6
      months of treatment and prevent further losses thereafter. The sequential
      biochemical changes indicate that nandrolone decanoate in patients on CST
      inhibits bone resorption without affecting or even increasing bone formation.
      Furthermore in patients on CST treatment the virilizing activity of nandrolone
      decanoate was virtually negligible at least within the 18 months of treatment.
      These results indicate that anabolic steroid administration may represent a
      rational and convenient strategy for preventing and treating CST-induced
      osteoporosis.

PMID- 8256457
TI  - Side effects of anabolic steroids and contraindications.
AB  - The endocrine side effects are mainly androgenic and concern particularly but not
      exclusively females and children. Depending on individual sensitivity, the dosage
      used and the androgenicity of the drug concerned, signs of virilization ranging
      from slight voice disturbances to severe derangement of reproduction can develop,
      the latter occurring in both sexes. Progestational effects are of little
      importance. Hepatic alterations are caused almost exclusively by 17 alpha
      alkylated steroids and can range from abnormal liver function tests to life
      threatening liver tumours. Atherogenic changes in the lipid-lipoprotein balance,
      again a domain of the 17 alpha-alkylated preparations, might increase the risk of
      coronary heart disease. The metabolic influences of anabolic compounds can--at
      excessive dosage levels--create a prediabetic condition and polycythaemia. The
      influence of anabolic agents on psyche and behavior in normal doses are mostly
      positive, rendering the drugs useful for adjuvant therapy in patients whose
      general condition is poor, irrespective of the origin. If given in excessive
      doses they can cause grave psychic and behavioral disturbances and possibly
      dependence. Anabolic-androgenic steroids should be used with caution in patients
      who are particularly sensitive to side effects, where fluid retention must be
      prevented, in subjects with liver diseases, skeletal metastases of mammary
      carcinoma, and when longitudinal growth is not completed. They are
      contraindicated in carcinoma of the prostate and mammary carcinoma in the male
      and their use should be discouraged in pregnancy and during lactation.

PMID- 8256458
TI  - Interactions of anabolic steroids.
AB  - Drug-drug interactions, or interference between drugs and other treatments,
      depend on many factors and are therefore difficult to predict. However, a number
      are clearly established in the case of anabolic-androgenic steroids. The
      beneficial interactions between anabolic steroids and radiotherapy or cytostatic
      drugs respectively are of therapeutic value. Adjuvant treatment with anabolic
      compounds in patients undergoing radiation and/or cytostatic therapy is
      beneficial because it can prevent or reduce depression of erythropoiesis,
      granulopoiesis and thrombopoiesis. It also diminishes protein catabolism,
      supports recovery, improves the general condition of the patient and minimizes
      radiation sickness. Potentially adverse interactions with anabolic steroids must
      be expected in the case of oral anticoagulants and antidiabetic drugs, since
      sensitivity to each of the latter is increased. This makes it particularly
      advisable to monitor patients receiving either oral anticoagulants or
      antidiabetic treatment concurrently with anabolic drugs.

PMID- 8256459
TI  - Patent foramen ovale and paradoxical embolization: a historical perspective.
AB  - The use of transesophageal echocardiography for intraoperative management of
      critically ill patients allows for routine evaluation of foramen ovale patency.
      The high prevalence of preoperatively unrecognized flow-patency of this structure
      has led investigators to emphasize the potential for paradoxical embolization in
      any patient undergoing anesthesia. This perspective led us to research earliest
      documentation of paradoxical embolization through a patent foramen ovale as a
      historical issue with present day relevance. This report examines the 1877 text
      of Julius Cohnheim in which he described a fatal case of paradoxical embolization
      to the middle meningeal artery. The 1880 manuscript of Moritz Litten documenting
      paradoxical embolization to the lower extremity is also presented. Both
      translations, to our knowledge, represent the first such representations of both
      the original 1877 edition of Cohnheim's work and Litten's journal article.

PMID- 8256460
TI  - Geographic distribution of white-tailed deer with ticks and antibodies to
      Borrelia burgdorferi in Connecticut.
AB  - Ticks and blood specimens were collected from white-tailed deer (Odocoileus
      virginianus) in Connecticut and analyzed to identify foci for Lyme borreliosis.
      Males and females of Ixodes scapularis, the chief vector of Borrelia burgdorferi,
      were collected from deer in five of eight counties during 1989-1991. Analysis by
      indirect fluorescent antibody (IFA) staining of midgut tissues showed that
      prevalence of infection was highest (9.5% of 367 ticks) in south central and
      southeastern Connecticut. Infected I. scapularis also were collected from
      southwestern regions of the state (12.1% of 99 ticks), but prevalence of
      infection in northern counties was considerably lower (0.8% of 124 ticks). Deer
      sera, obtained in 1980 and 1989-1991, were analyzed by an enzyme-linked
      immunosorbent assay or by IFA staining methods. Antibodies to B. burgdorferi were
      detected in sera collected from all eight counties in Connecticut. Deer had been
      infected by this spirochete in at least 50 towns, 17 (34%) of which are in south
      central and southeastern parts of the state. Borrelia burgdorferi is widely
      distributed in I. scapularis populations in Connecticut.

PMID- 8256461
TI  - The microvascular pathophysiology of chronic venous insufficiency.
AB  - Severe chronic venous insufficiency (CVI) demonstrates as chronic, hard-to-heal
      wounds of the lower extremity. The wound is the result of poor skin perfusion due
      to a complex series of pathologic events, often initiated by a deep vein
      thrombosis (DVT). As years pass, the DVT causes venous valvular damage and
      incompetence. The calf muscle pump fails to augment venous return, and venous
      blood pressure is chronically elevated upon standing. Mechanisms that normally
      prevent the transmission of venous hypertension back upstream to the dermal
      microcirculation are lost. Early dermal microvascular responses include increased
      fluid filtration and edema. An inflammatory response induces white cell
      activation and adhesion. It is thought that activated white cells are trapped in
      dermal capillaries and increase microvascular permeability. Plasma proteins leak
      into the tissue space, increasing the edema. Ischemic damage to the epidermis
      leads to epithelial cell necrosis and ulceration. The ulcer is often slow to
      heal, due to inadequate perfusion and delivery of substrates required for proper
      wound healing. Current treatments aim to improve calf pump function, reduce
      edema, improve perfusion, and enhance wound healing.

PMID- 8256462
TI  - A successful transplant of embryonic adrenal tissue in a patient with Addison's
      disease.
AB  - Well documented reports of the successful transplantation of human adrenal
      cortical tissue cannot be found in the literature. In 1951 we achieved the
      successful transplantation of human embryonic adrenal gland (cortical tissue) in
      a patient with symptomatic adrenal insufficiency (Addison's disease), apparently
      the first instance of histologically documented successful homografting of human
      adrenal cortex. Because of its historical pertinence, the authors, many years
      later, herein report on this case, which appeared in the senior author's medical
      thesis. The report must be viewed in the context of the existing clinical
      knowledge and technology available 40 years ago.

PMID- 8256463
TI  - Microangiopathy of cutaneous blood and lymphatic capillaries in chronic venous
      insufficiency (CVI).
AB  - The severity of microangiopathy in patients with chronic venous insufficiency
      (CVI) determines the extent of the trophic disturbances of the skin. Resulting
      from valvular incompetence of deep and/or perforating veins and the accompanying
      venous outflow obstruction caused by deep venous thrombosis (DVT), the increased
      ambulatory venous pressure heads are transmitted retrograde into the
      microvasculature of the skin at the ankle region. In the present study, we have
      assessed the changes in the cutaneous microvasculature by dynamic fluorescence
      video microscopy, fluorescence microlymphography, and transcutaneous oxygen
      tension (tcPO2) measurements. In mild forms of CVI, capillary density,
      morphologic characteristics, and tcPO2 are still normal. Fluorescent light
      intensity is, however, significantly increased, indicating an increased
      transcapillary diffusion of sodium fluorescein (NaF) as a marker for enhanced
      leakage of the capillaries in the early stage of the disease. The pericapillary
      halo diameters are significantly enlarged, compared to controls (p < 0.01). In
      the severe stages of CVI and in patients with venous ulcers, capillary
      thromboses, probably caused by endothelium-blood cell interactions, may lead to a
      reduced capillary density. In order to enlarge the exchange surface area, the
      remaining skin capillaries become tortuous (capillary tufts). Parallel to the
      reduced capillary number, tcPO2 decreases and can be extremely low at the ulcer
      rim or at white atrophy spots. Fibrin cuffs are not a specific finding for venous
      ulceration and do not significantly impair oxygen diffusion. Fluorescence
      microlymphography permits visualization of the lymphatic capillaries of the
      superficial skin. In severe stages of CVI, the lymphatic capillary network at the
      medial ankle area is destroyed, and the remaining lymphatic capillary fragments
      have an increased permeability to FITC-dextran with a molecular weight of
      150,000. These findings demonstrate a special lymphatic microangiopathy in CVI,
      suggesting an additional lymphatic component in the edema formation.

PMID- 8256464
TI  - Pathogenesis of chronic venous insufficiency and possible effects of compression
      and pentoxifylline.
AB  - It has been recognized for over 2000 years that ulceration of the leg may be
      associated with visible varices of the lower limb. More recent physiological
      investigation has shown that the pressure in the veins of the lower limb remains
      raised in patients with venous ulceration during ambulation, whereas in normal
      subjects the pressure in superficial veins falls to a low level. This elevated
      pressure appears to cause damage to the superficial capillaries in the skin
      culminating in the production of venous ulceration. Events in the dermal
      capillaries which result in skin destruction have yet to be fully defined.
      Pericapillary fibrin cuffs have been demonstrated histologically and suggested as
      a cause of diminished nutrition to the skin. White blood cells have been shown to
      accumulate in the lower limb of patients with venous disease and these
      accumulations are particularly located around the dermal capillaries. Activated
      white blood cells releasing free radicals and destructive enzymes may precipitate
      skin destruction. An understanding of these mechanisms may help to explain the
      efficacy of compression hosiery and bandaging as well as some of the new
      pharmacological agents which have been shown to influence venous ulcer healing.

PMID- 8256465
TI  - [Functional studies of the autonomic nervous system].
AB  - There are many methods to choose from in the investigation of the autonomic
      nervous system. The value of the individual tests to the clinician varies
      according to the method of investigation used. No one test can elucidate all the
      information needed for all functional disturbances. As a routine, measurement of
      blood pressure and heart rate reaction to active orthostasis and heart rate
      variation with deep breathing and the Valsalva manoeuvre can be useful. Spectral
      analysis of the heart rate is an easily performed test, only minimally disturbing
      for the patient, and is a valid means of investigation which may find a way into
      routine clinical use in the future.

PMID- 8256466
TI  - [The blood pressure lowering effect of bisoprolol, a beta 1-selective receptor
      blocker--a multicenter study in general practice conditions].
AB  - The antihypertensive efficacy and compatibility of 5 or 10 mg bisoprolol (Concor)
      was investigated in patients suffering from essential hypertension (stages I and
      II according to WHO) in a multicentre, open, non-randomized study. In total, 132
      patients were included in the study of 11 outpatient departments. Seventeen
      patients dropped out because of personal reasons or mistakes of the protocol. If
      the diastolic blood pressure did not decrease to values < or = 90 mm Hg at the
      end of the first period of treatment with 5 mg bisoprolol, the dose was doubled
      to 10 mg within the second period of antihypertensive treatment. At the end of
      the first period the mean blood pressure decreased from 161.5/104.1 to 141.4/90.8
      and after additional 4 weeks to 137.3/87.9 mm Hg. The mean heart rate decreased
      from 77.5 to 68.8 and 67.7/min, resp. The physicians who treated the patients
      rated the antihypertensive effect on 80.9% of the patients as good. Undesirable
      effects of bisoprolol were observed in 20 patients (15.2%). In total, bisoprolol
      has a good antihypertensive effect. It can be used in most patients as a
      monotherapeutic drug for treatment of stages I and II of hypertension with daily
      doses of 5 mg.

PMID- 8256467
TI  - [Arterial vascular diagnosis by Doppler pulse curve analysis of the first dorsal
      metatarsal artery].
AB  - In patients with peripheral arterial occlusive disease diagnostics by Doppler
      sonography at the toe arteries and by Doppler-pressure measurement at the ankle
      arteries is often difficult and sometimes impossible. Using the first dorsal
      metatarsal artery for Doppler-waveform analysis yields exact information on
      haemodynamically relevant circulatory disturbances. Painful ulcers, gangrene,
      oedemata, mediasclerosis, burns, plaster casts, posttraumatic or postoperative
      conditions prevent the application of cuffs at the lower leg or foot. This
      Doppler-waveform analysis evidently represents the degree and the specialties of
      a disturbed blood circulation and allows an additional assessment of the vessels
      distal from the ankle arteries and enables a functional test on the anastomosis
      of the artery tibialis posterior and the artery dorsalis pedis. Functional and
      pharmacological influences on the tone of the vessels can be shown. The typical
      diagnostic features of Doppler-wave-form analysis used at the proximal measuring
      points are also valid at the dorsal metatarsal artery. The results of own
      comparative investigations in 69 patients and 44 healthy test persons are
      demonstrated.

PMID- 8256468
TI  - [Alcohol-induced toxic hepatitis--a "free radical" associated disease. Lowering
      fatality by adjuvant antioxidant therapy].
AB  - Toxic liver diseases coincide with oxidative stress correlating positively with
      the seriousness of the course of disease. For the purpose of elucidating the
      pathogenic significance of an increased radical generation. 56 patients suffering
      from acute alcohol-toxic hepatitis of the clinical grade of seriousness B and C
      according to Child/Pugh were classified randomly into antioxidant subgroups (n =
      31) and control groups (= 25). The basis therapy being identical, the patients of
      the antioxidant group received additionally 600 mg of D-alpha tocopherol per day,
      200 micrograms of selenium and 12 mg of zinc. Due to the supplementation of
      antioxidants there were quicker significant changes in the concentration of
      bilirubin, malondialdehyde and of ammonia in the serum. In comparison with the
      control group the length of stay in hospital could be reduced by 6 days. In the
      control group the mortality rates amounted to 40% (10 of 25), in the antioxidant
      group to 6.5% (2 of 31). The results confirm the pathogenic significance of
      oxidative stress in alcohol-toxic liver disease because a distinct improvement of
      prognosis could be achieved by using a low-cost adjuvant antioxidant
      supplementation.

PMID- 8256469
TI  - [The effect of timing of surgical intervention on fatality of acute
      endocarditis].
AB  - Between 1/1986 and 5/1992 a total of 5283 surgical procedures involving
      extracorporal circulation were performed at our clinic, including 44 patients who
      underwent a total of 54 operations for acute endocarditis. On the basis of a
      retrospective study, this paper presents the pre-operative findings and the
      results of surgery in relation to the duration of the case history. Pathogenic
      microorganisms were successfully grown from the blood cultures of 63.6% (n = 31)
      of the patients. Among these microorganisms were viridans streptococci (n = 12),
      coagulase-negative staphylococci (n = 5), staph. aureus (n = 5), beta-haemolytic
      streptococci (n = 2) as well as combined infections (n = 2) and miscellanea.
      Preoperatively, 38 patients were in NYHA stage III or IV. Surgery resulted in an
      average improvement of 1.6 NYHA classes from NYHA 3.3 to NYHA 1.7. The total
      mortality rate was n = 13; early mortality was n = 3. The mean follow-up period
      was 3.9 years (minimum 5 weeks, maximum 6.4 years). The time elapsed between
      initial clinical manifestation of the disease and operation had a significant
      influence on mortality and on the prevalence of complications. Patients who died
      of endocarditis had a significantly longer case history (p < 0.05). The prognosis
      was poorer, according to our data, if the case history extended over more than 80
      days. Our results demonstrate clearly the necessity for such patients to be
      referred to a heart surgeon without delay.

PMID- 8256470
TI  - [Circulatory changes in acute sauna hyperthermia after heart transplantation].
AB  - The authors report on the influence of a single sauna-stay of patients following
      heart transplantation (HTX) during the rehabilitation phase III. Investigations
      of blood pressure, heart rate, changer in hemodynamics in the small and large
      vessels in 8 male patients following HTX (medium age: 42 years) showed that sauna
      hyperthermia is well tolerated. We watched significant decreases of blood
      pressure (systolic and diastolic values), an improvement of the microcirculation
      in the small vessels, an increase of the left ventricular ejection fraction
      (LVEF) and a decrease of the total peripheric vascular resistance (TPVR).
      Possibilities and limitations of sauna-therapy for the therapy of risk factors
      following HTX especially under immunosuppression are discussed. First results are
      demonstrated.

PMID- 8256471
TI  - [Chronic pollution with environmental toxins: formaldehyde].
AB  - Formaline is a colourless, strongly odoriferous gas. It is a very important basic
      component in chemical industry. It has become well known as a poison in
      residential areas due to its appearance in chipboard panels. Formaline causes a
      variety of acute and chronic toxic stress symptoms. In many cases the relation of
      formaline exposition and symptoms is difficult to demonstrate. The main keys to
      diagnosis are a very careful anamnesis and the cumulated appearance of symptoms.
      We intend to show several possible sources of stress symptoms caused by
      formaline, as well as diagnostic possibilities. This includes several methods of
      diagnostic assessing formaline concentration in the air, and several suggestions
      for the reduction of formaline emission.

PMID- 8256472
TI  - [Pancreas penetration by ofloxacin--a pilot study].
AB  - The use of antibiotics in patients with necrotizing pancreatitis is indicated
      since bacterial complications are the most common cause of death in this
      condition. Olfloxacin was studied in six patients regarding its permeation into
      pancreatic juice and bile and into pancreatic tissue in cases of chronic
      pancreatitis and pancreatic carcinoma. The peak concentrations in pancreatic
      juice (3.7 mg/l) and bile (12.9 mg/l) were found 20 minutes after i.v.
      administration of 3 mg/kg ofloxacin, these are 79 and 275% of the corresponding
      serum level, respectively. Pancreatic tissue concentrations varied between 54 and
      333% of serum values in relation to the removal time of specimens and to the
      stage of inflammation. After three days and five days of ofloxacin treatment with
      doses of 2 x 200 mg daily even in pancreatic necroses concentrations were
      detected between 0.8 and 3.7 mg/kg wet weight. This suggests that in all
      pancreatic compartments analyzed, sufficient antibacterial ofloxacin levels above
      the MIC of relevant germs were found. Therefore, from a pharmacokinetic point of
      view, ofloxacin could be a potentially effective drug in prophylaxis and therapy
      of bacterial infections of the pancreas.

PMID- 8256473
TI  - [Excretory pancreas function. Secretion of protein, calcium and citrate in
      probands with a normal pancreas and in patients with chronic pancreatitis].
AB  - Recent studies described an increased concentration of protein and calcium in
      association with a decreased concentration of citrate in pancreatic juice of
      patients suffering from chronic pancreatitis. These secretory changes may be of
      importance in the pathogenesis of chronic pancreatitis. The present study
      investigates pancreatic juices of 18 patients without pancreatic disease and 12
      patients in an early phase of chronic pancreatitis in order to detect changes of
      the exocrine function of the pancreas in an early stage of the disease. In all
      persons the pancreatic juice was collected by endoscopic cannulation of the main
      pancreatic duct after i.v. stimulation with secretin and pancreozymin. The
      outputs and concentrations of protein, calcium and citrate were estimated. All of
      these parameters did not differ in control subjects and patients with chronic
      pancreatitis by univariate statistical analysis. However, a multivariate analysis
      detects differences in the biochemical composition of the secretions of controls
      and patients with chronic pancreatitis (efficiency of discrimination = 100%).
      Both in controls and in patients with chronic pancreatitis two calcium fractions
      were found after secretin stimulation: one secretory protein-associated fraction
      of 94 nmol calcium/mg protein and a protein-independent calcium fraction of 0.248
      mmol/l, which diffuses paracellularly from the interstitium into the pancreatic
      juice. The results show that the secretory function of the exocrine pancreas is
      already disturbed in an early phase of chronic pancreatitis, whereas an increased
      lithogenity of the pancreatic juice cannot be detected.

PMID- 8256474
TI  - [In vitro contractility behavior of portal veins in normal rats and in rats with
      liver cirrhosis--effect of calcium antagonists and octreotide].
AB  - According to Poiseuille's law portal pressure is inversely related to r4. Thus,
      minor changes in radius dramatically influence intravascular pressure. Since the
      radius is actively regulated by contraction, this study elucidates in vitro
      contractility patterns of portal veins from healthy and liver cirrhotic rats. The
      results demonstrate that contractility amplitudes of portal veins from cirrhotic
      rats are increased in comparison to healthy animals. Calcium antagonists reduce
      amplitude and motility both in cirrhotic and healthy rats to the same degree. The
      same holds true for octreotide but significantly more in the cirrhotic group.
      Obviously, the maintenance of portal hypertension is supported by an active
      element of the portal vein, which can be controlled in vitro.

PMID- 8256475
TI  - Body acupuncture: effect on colonic function in chronic constipation.
AB  - Acupuncture has been claimed to be an efficacious treatment for chronic
      constipation, though there are no studies to prove this. We therefore
      investigated the effect of body acupuncture on stool frequency and colonic
      transit time of radiopaque markers in 8 constipated patients (58 +/- 6 years, 3
      female; vigorous straining necessary to open bowels without the use of laxatives
      for more than one year, total colonic marker transit > 60 h) in a control period
      and during a three weeks treatment period with six sessions. Acupuncture was
      performed as body acupuncture with electric needles (10 Hz, current titrated to
      individual threshold, 25 min each session) on acupuncture points Di4 [He Gu],
      Ma25 [Tian Shu], Le3 [Yuan], and B125 [Da Chang Yu]). Two patients dropped out
      during acupuncture because symptoms of constipation worsened. In the other 6
      patients, stool frequencies and colonic transit times were not significantly
      different during control and acupuncture period (0.38 +/- 0.09 vs. 0.40 +/- 0.14
      defecations per day +/- s.e.m., 95% confidence interval for the difference
      control minus acupuncture [-0.34; 0.30], and 97 +/- 17 vs. 108 +/- 24h, 95% Cl [
      50; 27]). Segmental transit times for right and left hemicolon, and rectosigmoid
      colon did not differ significantly either. In conclusion, acupuncture as
      performed in this study does not influence objective parameters of colonic
      function to a clinically relevant degree.

PMID- 8256476
TI  - [Transient insulin-dependent diabetes mellitus with alpha-interferon therapy in
      chronic active hepatitis].
AB  - Since alpha-interferon has been introduced an efficient therapy of chronic active
      hepatitis has become available for the first time. Among some of the treated
      patients, however, alpha-interferon therapy causes typical side effects. Fever,
      chills, loss of weight, fatigue as well as arthralgia, myalgia, loss of
      concentration and hematologic side effects have to be mentioned in particular. We
      report the occurrence of a diabetes mellitus under alpha-interferon therapy. The
      metabolic disorder gradually normalized after 3 weeks of antidiabetic treatment,
      although the interferon medication had been continued. We consider this disorder
      to be an effect caused by the alpha-interferon. The underlying mechanism might be
      an insulin resistance or an autoimmunologic defect. For that reason, when
      administering alpha-interferon, we recommend regular analyses of the blood sugar
      level during the regular patient monitoring.

PMID- 8256477
TI  - A combined biopsy-plugging device based on the Menghini- or Trucut needle for
      percutaneous liver biopsy: clinical experience.
AB  - Impaired blood clotting precludes percutaneous liver biopsy for histologic
      examination of liver tissue. The transjugular or laparoscopic approach are ways
      to reduce the risk of bleeding. These techniques, however, are laborious and
      confined to specialized centers. Methods of plugging the needle track with
      sealant presented so far are hampered by the need to leave either the cannula in
      situ or the need for a second percutaneous approach for the application of the
      sealant. We have tested a combined plugging-biopsy device allowing to perform the
      biopsy as a one-step procedure in patients with impaired clotting under
      laparoscopic vision control. In 37 patients either a modified Trucut or Menghini
      needle was tested. Handling of the Trucut needle proved easier. Tissue yield was
      satisfactory with both needles. Only one episode of bleeding was observed with a
      prototype Menghini needle. We conclude, that the combined plugging-biopsy device
      is a safe and reliable tool for obtaining liver tissue in patients with impaired
      blood coagulation.

PMID- 8256478
TI  - [Gas in the portal vein system of the liver. Value of ultrasound].
AB  - We report on 9 patients presenting with different diseases of varying severity,
      who were found to have hepatic portal venous gas (HPVG) identified by diagnostic
      ultrasonography. Intrahepatic gas was a shortlasting phenomenon, which could not
      be seen radiologically in most cases. Earlier beliefs that HPVG is a poor
      prognostic sign associated with high mortality, should be revised.

PMID- 8256479
TI  - [Growth factors in pancreatic cancer: the key to new therapy concepts for the
      future?].

PMID- 8256480
TI  - [Old times revived: surgery again for patients with reflux disease?].

PMID- 8256481
TI  - [Therapy of primary biliary cirrhosis with ursodeoxycholic acid].

PMID- 8256482
TI  - Chronic gastritis, prostaglandins and Helicobacter pylori.

PMID- 8256483
TI  - [The role of colonoscopy in patients with chronic inflammatory intestinal
      diseases. German Society of Digestive and Metabolic Diseases].

PMID- 8256484
TI  - [Biomechanical principles of diarthroses and synarthroses. III: Mechanical
      aspects of the tibiofemoral joint and role of the cruciate ligaments].
AB  - The tibiofemoral joint (TFJ) is force-locked. It takes its function as it is
      compressively loaded. The geometrical shape of the articulating surfaces and the
      acting force system (given by muscles and gravity) determine the kinematics as
      well as the quality and extent of static stability of the knee. The mechanism of
      the TFJ is derived from the anatomical shape of the articulating surfaces. In
      antero-posterior direction the joint guidance is structurally given by a
      stretched and overlapped dimeric link chain in lateral and medial region,
      respectively. Altogether, the two chains are linked up to a four-bar-chain (link
      quadrangle) that solely allows the tibia to strike backwards. The extent of
      individual extension can be rejected to morphological data of the femoral
      condylus. In squat position the extent of mechanical stability of the joint can
      be changed and even reversed to instability by a rotation of the resulting
      compressive joint force around the momentary rotational axis of the gear system
      while the joint position remains unaltered. Thus e.g. the process of
      straightening up is structurally explained. The cruciate ligaments do not bear
      any direct mechanical guiding function. They represent a sensor system which
      structurally resembles a mechanical bridge circuit. Beside detecting the degree
      of flexion it is able to monitor the indispensable contacting of the articulating
      surfaces. The menisci represent an additional, similarly working sensor system.
      At first approximation these two sensor systems are aligned in two planes which
      are perpendicular. Therefore they form a spatial sensor system. The presented
      theory is derived from mechanical, morphological, and physiological findings and
      gets evidence by measurements on knee loads during seated cycling.

PMID- 8256485
TI  - [Material properties of meniscus tissue and the effect of the menisci on the
      compression behavior of the knee joint].
AB  - Specimens of meniscus tissue were taken from different locations of the medial
      and lateral meniscus. They were tested to failure in the tensometer and force
      elongation diagrams were recorded. 28 meniscus specimens (14 medial, 14 lateral)
      gained at autopsy were available for testing. The posterior third of the medial
      meniscus and the middle third of the lateral meniscus were the strongest and
      stiffest parts of the meniscus. Yet local differences within one meniscus were
      only subtle. One clinical significance of these data is, that for replacement of
      the medial and lateral meniscus the same homogeneous material can be employed.
      Six tests under compression were carried out using six knee specimens gained at
      autopsy. Knee compression tests yielded different results after radial cutting of
      the meniscus, whereas partial meniscectomy had no effect on deformation and
      hysteresis. These biomechanical results support the concept of partial
      meniscectomy and preservation of the meniscal periphery. But they cannot be
      related to the problem of possible degenerative arthritis after partial
      meniscectomy.

PMID- 8256486
TI  - [The value of meniscus sonography--a study with reference to clinical and
      arthroscopic findings].
AB  - In a prospective study the sonographic findings of 250 patients were compared
      with the results of their clinical and arthroscopic examinations, in order to
      test the value of ultrasonography of the meniscus. At the same time the influence
      of interfering factors and the value of certain sonographic criteria were
      investigated. Diagnostic sensitivity of sonography proved to be 71% for the
      medial meniscus and 85% for the lateral meniscus. The division into parts made us
      realize that there was a high rate of errors. Sonography did not provide us with
      an essentially greater degree of information, except in certain cases such as
      ganglions, for example. Errors in diagnosis were evident in radial tears and in
      certain parts of the meniscus (Pars intermedia, Pars anterior and lateral
      meniscus). There is insufficient imaging especially in radial tears and cases of
      adiposis and osteoarthritis.

PMID- 8256487
TI  - [Reflex studies of the patellar tendon reflex in patients with varus
      gonarthrosis].
AB  - We discuss the role of the neuromuscular system following biomechanical
      circumstances for the development of osteoarthritis of the knee joint. We
      examined in 58 patients suffering from osteoarthritis with varus deformity and 22
      healthy people the latency and velocity of the patellar tendon reflex. We found
      with increasing age and by osteoarthritis of the knees shorter reflex latencies,
      that we see as disintegration of motor system.

PMID- 8256488
TI  - [Osteochondritis dissecans of the knee joint. Results of follow-up].
AB  - In a long-term follow-up examination (5-15 years postoperatively) clinical and
      radiological results after surgical treatment of osteochondritis dissecans of the
      knee of 97 patients with 109 osteochondritic lesions were controlled. The
      treatment consisted of retrograde removal of the subchondral osteonecrosis and 
      sclerosis with following autologous bone grafting in cases with intact hyaline
      cartilage. In cases of partial or total loosening of the osteochondritic lesion
      this procedure was done anterograde. For refixation different techniques such as
      fibrin glue or acylate glue were used. Using the classification of Arcq in 59.6%
      of the knee joints excellent and in 18.3% good results were obtained. Regarding
      the development of osteoarthritis in 56% no signs of osteoarthritis were visible.
      Worst results were obtained in knee joints in which non-resorbable acrylate glue
      was used for refixation of dissecates. In contrast to that patients in which
      loose dissecates were refixated with fibrin glue reached a significant better
      postoperative long-term result. In addition postoperative results were influenced
      by the age in which first symptoms were complained, by the stage of cartilaginous
      lesion, the kind of intraoperative technique and by additional morphological
      disturbances at the knee such as varus- or valgus mallaignment. In general for
      the treatment of osteochondritis dissecans of the knee an early operation before
      occurrence of cartilaginous lesions is recommended to avoid osteoarthritic
      changes. In cases of partial or complete loosening fibrin glue is recommended as
      the fixation technique of first choice.

PMID- 8256489
TI  - [Neurohistological studies in allogeneic cruciate ligament transplants as intra
      articular ligament replacement].
AB  - A multiplicity of surgical operations have been developed in an attempt to
      achieve satisfactory function after ACL repair. None of these procedures have
      been able to duplicate the fiber organization, attachment site anatomy,
      vascularity, or function of the ACL. 18 foxhounds received a deep frozen bone-ACL
      bone allograft and a ligament augmentation device (LAD). Neurohistological
      changes were evaluated 3, 6, and 12 months following implantation. Modified
      silver impregnation method and gold chloride technique were used to examine the
      presence of nerve endings and axons. Two morphological distinct mechanoreceptors
      were identified, and then were categorized as follows: free nerve-endings golgi
      like tendon receptors. Fine nerve endings were frequently ramified freely into
      ligament collagen bundles. Nerves and blood vessels were commonly associated.
      Like in normal ACL's both neuroreceptors were mostly located near the surface of
      the allografts and at both bony attachments. This study demonstrated the first
      histological evidence of viable mechanoreceptors and free nerve-endings in
      transplanted ACL-allografts, not previously reported in other ACL-substitutes
      using for ACL-reconstruction. Particularly important for post-op. rehabilitation,
      this technique may allow to reconstruct the proprioreceptive functions of normal
      anterior cruciate ligaments.

PMID- 8256490
TI  - [Is GSB knee prosthesis implantation for patellar problems still justifiable?
      Experiences and results based on 230 implanted GSB knee joint prostheses].
AB  - In our clinical the GSB-prosthesis has proved to be a good therapeutic concept.
      In 1988 we controlled 230 patients who had got GSB-prostheses in the years 1979
      1987. The average age of our patients was 75 years. Most times surgery had been
      done because of idiopathic osteoarthrosis, rarely because of post-traumatic or
      rheumatoid arthritis. Indications for surgery were usually severe pain, limited
      range of movement and deformities of the knee joint. In the beginning of the
      studied period we had implanted GSB-type I-prostheses, later we had implanted GSB
      type II-prostheses with or without femoropatellar surface. We achieved good
      results in pain reduction and in range of movement. However the major
      complications were caused by the patella. These patients had problems at climbing
      stairs, pain at the beginning of movements and at getting up from chairs. They
      presented with increased pain sensitivity at the tip of the patella and to
      friction of the patella. Regular radiological findings were severe destructions
      or fractures of the upper patellar pole. These problems led in 40 cases (17% of
      our cases) to reoperations until 1988 (At all we reoperated 50 times because some
      patients needed additional reoperations). According to our studies results there
      will be a need for reoperations in about 50 other cases. We discuss the following
      reasons for this high rate of severe patellar complications demanding re-surgery:
      1. Localisation of the patella: according to our studies the patella is
      frequently dranged cranially, seldom laterally. 2. Often we found an internal
      rotation of the tibia against the femur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256491
TI  - [Patient analysis of roentgenologically diagnosable skeletal manifestations of
      hemoblastoses].
AB  - A patient analyse about 672 adults and 164 children at the medical hospital of
      Leipzig University between 1978 and 1990 will be introduced here. The results
      will be discussed under following aspects: I. diagnostical criterions to limit
      the number of diseases, which may be the cause of roentgenological diagnosed bone
      lesions: 1. morbidity peak of the most common entities causing lesions of the
      skeleton, 2. how frequently one of these diseases causes bone alterations, 3.
      location and distribution of the skeleton manifestations, 4. character of these
      lesions. II. recommendations for the procedure enables to diagnose bone lesions
      by recognized haemoblastoses. III. criterions to evaluate by control-X-ray's of
      the skeleton changes the therapeutical effects in comparison with the dynamic of
      the disease causing the bone lesions. It will be accentuate the importance to
      consider more-frequently haemoblastoses in the differential diagnosis of bone
      lesions.

PMID- 8256492
TI  - [Tumor simulating manifestations of renal osteopathy: differential diagnosis and
      follow-up clinical examples].
AB  - The course of renal osteodystrophy possibly includes changes, which can
      mistakenly considered malignant. Especially dialysis-associated tumoral
      calcinosis may mislead to an inadequate aggressive surgical procedure.
      Spontaneous involution of these lesions takes place after subtotal
      parathyroidectomy. Brown tumors subsequent secondary hyperparathyroidism are
      extremely rare. During maintenance hemodialysis frequently appearing intraosseous
      cysts develop secondary to beta-2-microglobulin-amyloidosis. Surgery only should
      be performed in case of occurring pathologic fractures. Other cases are treated
      conservatively under continuous nephrologic supervision.

PMID- 8256493
TI  - [Use of the tumor prosthesis in secondary neoplastic destruction of the proximal
      end of the femur].
AB  - Total hip arthroplasty was performed with PMMA-augmented tumor prostheses in 42
      individuals suffering from metastatic destruction of the proximal end of the
      femur at the Orthopedic University Hospital Mainz from 1980 to 1992. Neoplastic
      lesions had been triggered by carcinomas of the breast in 25 female patients. 24
      of our patients presented with pathologic fractures. In all patients capable of
      walking preoperatively early mobilization could be attained by total hip
      arthroplasty. Pain relief was achieved in each patient. Resection of the major
      trochanter and, partially, of the pelvitrochanteric muscle sleeve entailed
      luxation of the prosthesis six times in 5 individuals during the first
      postoperative two months; closed reduction was practicable in all of them.
      Postoperative survival time amounted to an average of 10.5 months. Leg length and
      hip function were successfully re-established by implanting tumor prostheses
      after resection of the proximal part of the femur.

PMID- 8256494
TI  - [The Borggreve rotation-plasty. A surgical method in therapy of malignant bone
      tumors and functional results].
AB  - From 1980 to 1992, 39 Borggreve-rotation-plasties were performed in patients with
      malignant bone tumors at the Orthopaedic Clinic of the University of Hamburg. The
      rotation-plasty was first published in 1930 by Borggreve. Salzer (Wien) described
      the method in 1981 for the operative treatment of osteosarcomas about the knee.
      The rotation-plasty is feasible for tumors of the distal femur, even when other
      limb-saving procedures are impossible, e.g. due to skip metastases, insufficient
      soft tissue coverage or involvement of the knee joint. The procedure was done on
      26 female and 13 male patients, the age ranging between 7 and 45 years with a
      mean age of 17 years. The histological diagnosis was osteosarcoma in 36 cases,
      MFH, Ewing's sarcoma and Giant cell tumor in one case, respectively. The
      operative technique was slightly modified, compared to the method described
      originally by Salzer. The range of error of the different preoperative imaging
      procedures was evaluated and compared with the tumor extent in the resected
      specimen. MRI was found to be most precise. We saw no local recurrencies. Three
      patients had early thromboses, two of those had to be amputated, slow
      preoperative compression of the popliteal vein being the main cause in both. One
      patient developed a lymphatic fistula ten years postoperatively, which was
      eliminated in a second operation. All patients are followed routinely in the
      oncologic outpatient service. The functional results were rates "excellent" or
      "good" for all patients in six of seven categories, according to the Enneking
      evaluation system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256495
TI  - [Tendinosis calcarea--results of treatment with needling].
AB  - In a prospective study, 33 patients with calcifying tendinitis had a needling in
      local anaesthesia performed under control of an image converter. There was at
      least a one year follow-up period. Resorption of the hydroxyapatite deposits was
      seen in 23 instances; 75% of all patients were free of symptoms or had
      considerably improved (Table 3). For better assessment of these results we
      embarked on an additional retrospective study observing the spontaneous evolution
      of 235 hydroxyapatite deposits for 3 years on average. On the x-ray, these
      deposits had a characteristic appearance and could be classified into one of
      three types: either sharply outlined and densely structured (type I), or with
      cloudy limitations and transparent in structure (type III). In addition we saw
      deposits combining the features of both of the above named types (type II) (Table
      5, Fig. 6). Based on this classification, a clear correlation was revealed to
      exist between initial x-ray findings and the frequency of resorption after
      needling: with type I, complete resorption was seen in 33% of the cases, with
      type II in 71%, and with type III in 85% of the cases (Table 6). With type II,
      however, only half of the patients were free of symptoms. Surgical removal of the
      hydroxyapatite deposits became necessary in 3 patients because of persisting
      heavy pains. As complication we observed intraoperatively an incomplete tear of
      the rotator cuff, the relation of which to the needling remained unsure. In this
      context, the question is discussed whether calcifying tendinitis and rupture of
      the rotator cuff may represent two disease entities of identical origin.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256496
TI  - [Is tendinosis calcarea associated with HLA-A1?].
AB  - Increased frequency of HLA-A1 in calcifying tendinitis? In a study with 46
      patients Sengar et al. observed an association of calcifying tendinitis and HLA
      A1 in 50% (normal regional frequency: 26.7%). In our study with 55 patients we
      found a presence of HLA-A1 in only 32.7% (normal regional frequency: 30.5%),
      there was no increased frequency.

PMID- 8256497
TI  - [Initial experiences with extracorporeal shockwave lithotripsy (ESWL) in
      treatment of tendinosis calcarea of the shoulder].
AB  - In a prospective investigation the use of high energetic shock waves for
      treatment of chronical painful calcareous tendinitis of the shoulder was examined
      in a pilot group of 5 patients. The deposits were localized by sonography.
      Immediately after treatment 1 patient felt complete release of pain, the calcium
      deposit had disappeared on the x-ray control one day after treatment. In 3 cases
      pain release and elimination of the calcification appeared during 6 weeks after
      treatment. One patient showed only radiological disintegration of the
      calcification with no release of pain.

PMID- 8256498
TI  - Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen vector
      systems.
AB  - Cholera toxin (CT) and the analogous heat-labile enterotoxin (LT) from
      Escherichia coli have several immunomodulating effects which alone or in
      combination might explain their strong adjuvant action in stimulating mucosal IgA
      and other immune responses to admixed unrelated antigens after oral immunization.
      These effects include, depending on animal species and experimental systems,
      enhanced antigen presentation by a variety of cell types; promotion of isotype
      differentiation in B cells leading to increased IgA formation; and complex
      stimulatory as well as inhibitory effects on T-cell proliferation and lymphokine
      production. This adjuvant activity appears to be closely linked to the ADP
      ribosylating action of CT and LT associated with enhanced cyclic AMP formation in
      the affected cells, and thus it may prove difficult to eliminate the enterotoxic
      activity without loss of adjuvanticity. However, through a separate mechanism, as
      an antigen-carrier system providing specific binding to epithelium including the
      M cells of intestinal Peyer's patches, both CT and its non-toxic binding subunit
      moiety (CTB) have been shown to markedly enhance the mucosal immune response to
      various foreign antigens or epitopes covalently linked to these molecules. This
      gives promise for the future use of CTB or related non-toxic binding derivatives
      as vehicles to facilitate induction of mucosal immune responses to a broad range
      of antigens for human vaccination purposes.

PMID- 8256499
TI  - Recombinant secreted haemagglutinin protects mice against a lethal challenge of
      influenza virus.
AB  - Balb/c mice were immunized with 2 x 2 micrograms of purified recombinant secreted
      haemagglutinin, derived from the A/Victoria/3/75 (H3N2) virus. In the first
      immunization, Ribi adjuvant was used, while for the booster injection a
      monophosphoryl lipid A/muramyl dipeptide combination was chosen. Mice immunized
      in this way were 90-100% protected against a challenge with 20 LD50 of mouse
      adapted, homologous virus (strain X47). Bromelain-solubilized haemagglutinin gave
      only 70% protection under comparable conditions.

PMID- 8256500
TI  - Haptoglobin polymorphism and the immune response after hepatitis B vaccination.
AB  - One hundred healthy Caucasian medical students (age 22 +/- 1 years) were
      vaccinated with a recombinant hepatitis B vaccine and their haptoglobin types
      were determined. A relationship between haptoglobin type and immune response to
      the vaccine was observed. Subjects with a 2-2 haptoglobin phenotype produced
      significantly lower hepatitis B antibody titres than those having a 1-1 or 2-1
      haptoglobin phenotype. The haptoglobin phenotypes not only influenced the
      magnitude but also the kinetics of the anti-HBs response. For all haptoglobin
      types, haptoglobin concentration and immune response to the vaccine behaved
      independently.

PMID- 8256501
TI  - GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside
      GD3.
AB  - The gangliosides of melanoma and other tumours of neuroectodermal origin are
      suitable targets for immune intervention with tumour vaccines. The optimal
      vaccines in current use contain ganglioside plus bacillus Calmette-Guerin and
      induce considerable morbidity. We have screened a variety of new adjuvants in the
      mouse, and describe one antigen-delivery system, proteosomes, which is especially
      effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form
      multimolecular liposome-like vesicular structures termed proteosomes which can
      readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal
      GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse
      is determined. Interestingly, the use of potent immunological adjuvants in
      addition to proteosomes augments the IgM and IgG antibody titres against OMP in
      these vaccines but GD3 antibody titres are unaffected. The application of
      proteosomes to enhance the immune response to GD3 extends the concept of the
      proteosome immunopotentiating system from lipopeptides to amphipathic
      carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety
      of meningococcal OMP in humans and the data in mice presented here suggest that
      proteosome vaccines have potential for augmenting the immunogenicity of
      amphipathic tumour antigens in humans.

PMID- 8256503
TI  - Expression and immunogenicity of the V3 loop from the envelope of human
      immunodeficiency virus type 1 in an attenuated aroA strain of Salmonella
      typhimurium upon genetic coupling to two Escherichia coli carrier proteins.
AB  - A peptide comprising residues glu293 to ser334 from the principal neutralization
      determinant (V3 loop) of the envelope of human immunodeficiency virus type 1
      (HIV1 LAVBRU isolate) has been inserted within internal permissive sites of
      either LamB or MalE, two envelope proteins from Escherichia coli K12. The MalE
      hybrid protein (MalE133-V3 loop) was stably expressed in the periplasm of
      Escherichia coli K12, and the V3 loop peptide was detectable on the surface of
      the native protein by an anti-gp160 monoclonal antibody (mAb 110-A). The
      disulfide bridge between the two cysteines of the loop was formed. In contrast,
      genetic coupling to the outer membrane protein LamB did not allow the expression
      of a stable hybrid protein, and major proteolytic cleavage products of the
      LamB153-V3 loop were detected by mAb 110-A. The two plasmid-encoded hybrid genes
      were transferred to an aroA mutant of Salmonella typhimurium. Constitutive
      expression of the MalE133-V3 loop had no detectable effect on cell growth and on
      the survival in vivo of the recipient strain. The LamB153-V3 loop was not stably
      expressed in Salmonella, either in vitro or in vivo. Live recombinant salmonellas
      expressing MalE-V3 and LamB-V3 loop hybrids were used to immunize mice. The MalE
      V3 loop hybrid induced anti-HIV1 envelope antibodies detectable by Western blot
      and ELISA, while the anti-HIV1 envelope antibodies induced by the LamB-V3 loop
      hybrid were only detectable by Western blot. In addition, purified MalE-V3 loop
      hybrid protein was able to stimulate in vitro and induce in vivo a V3 loop
      specific T-cell proliferative response.

PMID- 8256502
TI  - Transferrin-binding proteins isolated from Neisseria meningitidis elicit
      protective and bactericidal antibodies in laboratory animals.
AB  - Transferrin-binding proteins (Tbps) were affinity-isolated from group B Neisseria
      meningitidis strain B16B6 and used to raise specific antisera. Administration of
      the antisera to mice loaded with human transferrin before bacterial challenge
      significantly protected the animals from death. In active immunization studies,
      mice received three 25 micrograms injections of purified Tbps over a period of 28
      days, 7 days after which they were challenged with N. meningitidis. The survival
      rate in immunized mice was much higher than in control groups. In both active and
      passive immunization experiments mice were protected against at least 100 LD50. A
      specific Tbp antiserum was highly bactericidal against the parent strain and
      against approximately half of the strains tested.

PMID- 8256504
TI  - Hepatitis B vaccination and booster in predialysis patients: a 4-year analysis.
AB  - Patients undergoing chronic haemodialysis are at increased risk for infection
      with hepatitis B virus (HBV), but response to currently available vaccines is
      suboptimal. We undertook a 4-year prospective study of the efficacy of hepatitis
      B vaccine in patients with renal insufficiency, who were not yet dialysis
      dependent. A booster dose of Recombivax HB was given at 3 or 4 years to those
      whose antibody levels fell below a predetermined point. Progression to dialysis
      was associated with poorer initial response to vaccination compared with those
      remaining dialysis-independent, but response to booster immunization was
      favourable in both groups. It is concluded that immunization of predialysis
      patients and subsequent booster vaccine results in a more favourable antibody
      response than has been seen historically in haemodialysis patients. Local
      endemicity and cost of vaccine should be considered when determining the best
      strategy for HBV immunization of patients with chronic renal failure.

PMID- 8256505
TI  - Expression of human immunodeficiency virus type 1 Nef antigen on the surface of
      acutely and persistently infected human T cells.
AB  - The authors have previously shown the role of human immunodeficiency virus type 1
      (HIV-1) Nef protein as a growth inhibitor to CD4+ T lymphocytes. We now report
      that the Nef antigen is partly expressed on both acutely and persistently
      infected human T cells. To investigate the cell surface expression of the Nef
      antigen, murine monoclonal antibodies (mAbs) were prepared by immunization with a
      recombinant Nef protein. The recombinant Nef was expressed by a baculovirus
      expression system as a truncated Nef protein with 22 kDa containing the middle to
      the C-terminus. Three clones were found to produce mAbs with IgM isotype against
      Nef protein by ELISA with the same truncated Nef. All these mAbs reacted on
      immunoblotting with two forms of Nef, 25 kDa and 27 kDa, in an HIV-1-infected
      human T-cell line and with the 27 kDa Nef in retroviral vector-infected mouse
      fibroblasts expressing a full-length Nef protein. Membrane immunofluorescence and
      flow cytometry with these mAbs revealed the Nef antigen to be expressed, at least
      in part, on the surface of these cells. Thus, the cell-surface form of Nef might
      play an important role in the selective depletion of CD4+ cells in HIV-1
      infection.

PMID- 8256506
TI  - A genetically engineered vaccine against the alpha-toxin of Clostridium
      perfringens protects mice against experimental gas gangrene.
AB  - Fragments of the alpha-toxin of Clostridium perfringens have been produced using
      genetic manipulation techniques. Antibody which cross-reacted with the alpha
      toxin was induced after immunization with fragments representing the N- (Cpa1
      249) and C-terminal (Cpa247-370) domains of the toxin. Smaller fragments of the
      alpha-toxin did not induce cross-reacting antibody. Anti-Cpa1-249 serum
      neutralized phospholipase C activity but not haemolytic activity of the toxin.
      Anti-Cpa247-370 serum neutralized both the phospholipase C and haemolytic
      activities. Only immunization with Cpa247-370 induced protection against the
      lethal effects of the toxin. Immunization with Cpa247-370 also provided
      protection in a mouse model against at least 10 LD100 doses of C. perfringens
      type A. This result confirms the essential role of this toxin in the pathogenesis
      of gas gangrene.

PMID- 8256507
TI  - Protective activity of a murine monoclonal antibody against European bat
      lyssavirus 1 (EBL1) infection in mice.
AB  - A mouse model was designed to test in vivo the efficacy of rabies immune
      globulins and specific neutralizing monoclonal antibodies to prevent European bat
      lyssavirus 1 infection. Human or equine rabies immune globulins previously found
      to contain variable amounts of neutralizing bat lyssavirus crossreactive
      antibodies were passively transferred to mice receiving intramuscularly a lethal
      dose of bat lyssavirus type 1. Immune globulins did not protect mice well against
      bat lyssavirus 1 whereas they reduced the mortality caused by rabies virus. In
      contrast, mice inoculated with bat lyssavirus 1 or rabies virus survived when
      passively immunized with bat lyssavirus 1 specific monoclonal antibody (mAb 8-2).
      This monoclonal antibody, an IgG2 alpha, recognized an epitope located in the
      antigenic site IIa of rabies glycoprotein. A mutation replacing the lysine 198 by
      glutamate in a rabies variant abrogated sensitivity to this neutralizing
      antibody. Because of its broad neutralizing spectrum against wild virus isolates,
      including European bat lyssaviruses, this monoclonal antibody should be a good
      candidate for rabies immune globulin replacement. It could improve efficacy of
      rabies vaccination, used either alone or in conjunction with human rabies immune
      globulins or monoclonal antibody cocktail to supplement their lack of
      crossreactivity to European bat lyssavirus 1.

PMID- 8256508
TI  - Role of EIPV in 1988 Israel polio outbreak.

PMID- 8256509
TI  - Measles vaccine controversy.

PMID- 8256510
TI  - Comparison of the biochemical and biological functions of tyrosine phosphatases
      from fission yeast, budding yeast and animal cells.
AB  - In a previous communication, we have shown that two protein tyrosine tyrosine
      phosphatases (PTPases) from fission yeast, pyp1+ and pyp2+, act as novel
      inhibitors of mitosis upstream of the wee1+/mik1+ pathway (Ottilie et al., 1992).
      Here we describe that both genes possess intrinsic PTPase activity as judged by
      in vitro PTPase assays using 32P-labeled Raytide as a substrate, and that 32P
      labeled p107wee1 is an in vitro substrate for pyp1. To compare the biological
      activity of pyp1 and pyp2 to that of other known PTPases, we expressed the
      budding yeast PTP1 and human placental phosphatase 1B (PTP1B) genes in either a
      cdc25-22 or wee1-50 genetic background and established that, in contrast to pyp1+
      and pyp2+, Saccharomyces cerevisiae PTP1 and human PTP1B complement the cdc25
      mutant, opposing the wee1+/mik1+ pathway.

PMID- 8256511
TI  - Treatment of yeast cells with wall lytic enzymes is not required to prepare
      chromosomes for pulsed-field gel analysis.

PMID- 8256512
TI  - KTR2: a new member of the KRE2 mannosyltransferase gene family.
AB  - The KTR2 gene from Saccharomyces cerevisiae was identified by polymerase chain
      reaction amplification of genomic DNA using primers derived from regions of high
      homology between the products of three yeast genes, KRE2, YUR1 and KTR1. The
      product encoded by the KTR2 gene is a predicted type II membrane protein of 425
      amino acid residues with a short cytoplasmic N-terminus, a membrane-spanning
      region and a large lumenal domain containing residues with a short cytoplasmic N
      terminus, a membrane-spanning region and a large lumenal domain containing four
      potential N-glycosylation sites. Ktr2p has 58% identity with Yur1p, 39% with
      Ktr1p and 34% with Kre2p. One member of this gene family, KRE2 (also known as
      MNT1; Hausler and Robbins, 1992), encodes an alpha-1,2 mannosyltransferase which
      adds the third mannose onto O-linked glycoprotein side-chains (Hausler et al.,
      1992). In contrast to KRE2 null mutants, which produce shortened (two-mannose)
      chains, mutants harboring a KTR2 gene disruption synthesize O-linked chains with
      the wild-type patterns of five mannose residues. A null mutation in KTR2 leads to
      partial resistance to killer toxin and hints that KTR2, which encodes a putative
      mannosyltransferase, is involved in extracellular matrix assembly.

PMID- 8256513
TI  - Regulation of the amino acid permeases in nitrogen-limited continuous cultures of
      the yeast Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae, there is a general amino acid permease,
      regulated by nitrogen catabolite repression, and several specific permeases whose
      nitrogen regulation is not well understood. In this study, we used continuous
      cultures to analyse the effect of nitrogen limitation and pH on the activity of
      general and several specific amino acid permeases. General permease activity was
      maximal in severe nitrogen limitation and diminished 400-fold in cells grown
      under nitrogen excess. For the specific permeases, the maximal uptake activity
      was found between mild limitation and nitrogen excess, while very small activity
      was detected under strict limitation. These results indicate that the nitrogen
      regulation of the general and the specific amino acid carriers is coordinated in
      such a way that no redundancy exists in amino acid transport. The regulation of
      the specific permeases was similar to that found for a system with anabolic
      function in nitrogen metabolism. All of these permeases are supposed to work
      through a proton symport mechanism, and thus rely on pH gradients to carry out
      their function. We studied the effect of pH on the kinetic constants of the
      general permease. Our results show that the effect of pH on the Km was different
      for acidic, neutral and basic amino acids, while the effect on Vmax was
      independent of the electrical charge of the amino acids.

PMID- 8256514
TI  - Transcriptional regulation by glucose of the yeast PMA1 gene encoding the plasma
      membrane H(+)-ATPase.
AB  - The yeast plasma membrane H(+)-ATPase generates a membrane electrochemical
      gradient which is required for the secondary uptake of nutrients. Although the
      ATPase has previously been shown to be post-translationally regulated in response
      to the availability of glucose, there has been no evidence to date for
      transcriptional regulation of the ATPase gene (PMA1). In this work, we have
      examined the pool of newly synthesized ATPase that accumulates in secretory
      vesicles en route to the cell surface in the temperature-sensitive secretory
      mutant sec6-4, and have observed changes in the level of ATPase polypeptide as a
      function of the glucose concentration in the growth medium. In parallel, there
      were rapid and reversible changes in the levels of ATPase mRNA. Finally, when
      cells were grown on a variety of carbon sources, the amount of ATPase polypeptide
      was proportional to the specific growth rate, suggesting that PMA1 expression is
      adjusted according to the metabolic state of the cell. These results complement
      the findings of Capieaux et al. (Capieaux, E., Vignais, M.-L., Sentenac, A. and
      Goffeau, A. (1989). J. Biol. Chem. 264, 7437-7446), who show that the
      transcriptional factor TUF/RAP1 binds to upstream activating sequences in the
      PMA1 gene. Taken together, the results suggest a model in which transcriptional
      regulation of the ATPase gene by glucose is mediated by TUF/RAP1.

PMID- 8256515
TI  - Two distinct yeast proteins are related to the mammalian ribosomal polypeptide
      L7.
AB  - The RLP7 gene of Saccharomyces cerevisiae was cloned, sequenced and localized to
      the right arm of chromosome XIV, close to the centromere. It encodes a predicted
      polypeptide (RLP7p) of 322 amino acids, with a calculated molecular mass of 36
      kDa and an isoelectric point of 9.6. Putative open reading frames very similar to
      RLP7 are present in two other yeasts, Kluyveromyces lactis and Candida utilis.
      The RLP7p gene product has significant sequence similarity to the S. cerevisiae
      YL8 polypeptide of the large ribosomal subunit (Mizuta et al., 1992), itself
      homologous to the L7 subunit of mammalian ribosomes. However, RLP7p and YL8 do
      not functionally replace each other, since an rlp7-delta::HIS3 strain is
      completely inviable. Judging from its predicted mass, isoelectric point and amino
      acid sequence, RLP7p does not correspond to any ribosomal component biochemically
      identified so far in S. cerevisiae, and also differs from all known ribosomal
      proteins by the low codon usage bias of its gene.

PMID- 8256516
TI  - Theoretical analysis of the effects of mitotic crossover in large yeast
      populations.
AB  - In a diploid yeast population which is heterozygous for a given marker, A1A2,
      mitotic crossover (mit. c.o.) between the centromere and the marker will give
      rise to homozygous daughter cells, A1A1 and A2A2. Since this causes a decrease in
      the frequency of A1A2 cells, mit. c.o. is an important population genetic process
      in vegetatively propagated yeast cultures. The effect of mit. c.o. is
      counteracted by mutations and, in the case of heterosis, by selection. We present
      a mathematical analysis of these interactions.

PMID- 8256517
TI  - Mapping of the RIB1 and RIB7 genes involved in the biosynthesis of riboflavin in
      Saccharomyces cerevisiae.

PMID- 8256518
TI  - PFK2, ISP42, ERG2 and RAD14 are located on the right arm of chromosome XIII.
AB  - An 11 kb yeast DNA insertion isolated from a genomic library by complementation
      of a phosphofructokinase-deficient strain was used as a source for a partial
      sequence analysis. Four genes were shown to reside on this fragment, namely PFK2,
      ISP42, ERG2 and RAD14. PFK2 was mapped previously to the right arm of chromosome
      XIII, locating the latter three genes to the same chromosome.

PMID- 8256519
TI  - The nucleotide sequence of a 2.1 kb fragment from chromosome VI of Saccharomyces
      cerevisiae identifies a tRNA(Gly) gene, part of a delta element and a palindromic
      sequence.
AB  - The nucleotide sequence was determined of a 2.1 kb DNA fragment located at
      approximately 35 kb to the right of the centromere of chromosome VI from
      Saccharomyces cerevisiae. Analysis revealed the presence of a tRNA(GLy) gene,
      part of a delta element and a remarkable palindromic sequence. The longest open
      reading frame found encodes a putative protein of 195 amino acids. Although the
      fragment was isolated by hybridization to a human diacylglycerol kinase cDNA, no
      evidence was obtained for the presence of a gene encoding diacylglycerol kinase.

PMID- 8256520
TI  - Identification of two divergently transcribed genes centromere-proximal to the
      ARG4 locus on chromosome VIII of Saccharomyces cerevisiae.
AB  - We have sequenced a 3296 bp segment of the chromosome VIII adjacent to the 3' end
      of the ARG4 gene. This segment contains two divergently oriented open reading
      frames (YSC83 and YSC84). Northern blot analysis showed the presence of
      transcripts corresponding to these two open reading frames in vegetative cells.
      Levels of these transcripts increase five to ten-fold during sporulation. These
      two genes are not essential for vegetative growth or sporulation. Analysis of the
      putative protein products on the SwissProt database revealed that the C-terminal
      region of the Ysc84 protein contains a putative SH3 domain.

PMID- 8256521
TI  - GUT2, a gene for mitochondrial glycerol 3-phosphate dehydrogenase of
      Saccharomyces cerevisiae.
AB  - A gut2 mutant of Saccharomyces cerevisiae is deficient in the mitochondrial
      glycerol 3-phosphate dehydrogenase and hence cannot utilize glycerol. Upon
      transformation of a gut2 mutant strain with a low-copy yeast genomic library,
      hybrid plasmids were isolated which complemented the gut2 mutation. The
      nucleotide sequence of a 3.2 kb PstI-XhoI fragment complementing a gut2 mutant
      strain is presented. The fragment reveals an open reading frame (ORF) encoding a
      polypeptide with a predicted molecular weight of 68.8 kDa. Disruption of the ORF
      leads to a glycerol non-utilizing phenotype. A putative flavin-binding domain,
      located at the amino terminus, was identified by comparison with the amino acid
      sequences of other flavoproteins. The cloned gene has been mapped both physically
      and genetically to the left arm of chromosome IX, where the original gut2
      mutation also maps. We conclude that the presented ORF is the GUT2 gene and
      propose that it is the structural gene for the mitochondrial glycerol 3-phosphate
      dehydrogenase.

PMID- 8256522
TI  - The complete sequence of a 6794 bp segment located on the right arm of chromosome
      II of Saccharomyces cerevisiae. Finding of a putative dUTPase in a yeast.
AB  - The DNA sequence of a 6794 bp fragment located at about 100 kb from the right
      telomere of chromosome II from Saccharomyces cerevisiae has been determined.
      Sequence analysis reveals five open reading frames. One is the ARO4 gene encoding
      the 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase. Another presents strong
      homology with the S5 ribosomal protein from bacteria. The open reading frame
      YBR1705 shows significant homology with dUTPase, suggesting for the first time
      the existence of such an enzyme in S. cerevisiae.

PMID- 8256523
TI  - The RHO4a and NUD1 genes on Saccharomyces cerevisiae chromosome XI.
AB  - Sequence analysis of a 4 kb fragment from the right arm of Saccharomyces
      cerevisiae chromosome XI, in combination with Northern hybridization experiments
      revealed the presence of two genes, designated RHO4a and NUD1. The first gene
      encodes a 32 kDa protein showing significant sequence similarity with members of
      the ras family. Its 3'-terminal sequence is virtually identical to a sequence
      published previously as the RHO4 gene [Matsui and Toh-e, Gene 114 (1992), 43-49],
      which, however, appears to start at an internal ATG codon. The RHO4a sequence
      also overlaps the 5'-terminal sequence of the RNC1 gene [Chow et al., Nucl. Acids
      Res. 20 (1992), 5215-5221] proposed to encode the yeast yNucR endo/exonuclease.
      The remainder of this RNC1 gene overlaps with the 5'-end of the NUD1 gene.
      However, the RNC1 sequence lacks a portion of 276 bp that in our fragment is part
      of the intergenic region separating RHO4a and NUD1. From these results we
      conclude that the proposed RNC1 gene is the result of a cloning artefact and that
      the yNucR protein is instead encoded by the NUD1 gene.

PMID- 8256525
TI  - Current awareness on yeast.

PMID- 8256524
TI  - DNA sequence analysis of a 17 kb fragment of yeast chromosome XI physically
      localizes the MRB1 gene and reveals eight new open reading frames, including a
      homologue of the KIN1/KIN2 and SNF1 protein kinases.
AB  - We report in this paper the sequence of a part of chromosome XI of Saccharomyces
      cerevisiae. This 17 kbp nucleotide sequence represents the right half of cosmid
      pUKG151 and contains nine open reading frames, YKL453, 450, 449, 448, 445, 443,
      442, 441 and the 5' part of YKL440. YKL440 was previously identified as the MBR1
      gene and plays a role in mitochondrial biogenesis. YKL443 is a homologue of the
      yeast serine-rich protein (SRP1), while YKL453 presents strong homologies with
      the KIN1/KIN2/SNF1 kinase family. It must be pointed out that the size of this
      gene is well above average for yeast.

PMID- 8256526
TI  - Social and preventive medicine: a scientific approach to questions of practical
      relevance.

PMID- 8256527
TI  - Research and teaching in social and preventive medicine and in public health.
AB  - Both public health and social and preventive medicine are characterised by the
      common goal of promoting, maintaining and improving health and preventing
      disease, and both are concerned with a population-related, preventive and
      environmental perspective. But whereas public health is interdisciplinary and
      goes far beyond the medical focus, social and preventive medicine is medically
      based and forms a bridge between public health and medical practice. Research in
      a department of social and preventive medicine serves to support preventive and
      medico-social activities in medical practice as well as in public health. This is
      illustrated by results from research conducted at the author's department during
      the last twenty years. Examples are research in support of smoking cessation
      activities, and research used for the planning of care for the elderly. Both the
      research and the teaching activities of the department take into account the
      population focus of public health as well as the focus on individual medicine in
      clinical practice.

PMID- 8256528
TI  - The public health perspective of social and preventive medicine.

PMID- 8256529
TI  - Epidemiological approach to the explanation of social differentiation in
      mortality: the Whitehall studies.
AB  - A consistent feature of mortality statistics in England and Wales are the social
      class differences which have even widened in the decade from 1971 to 1981. Two
      large studies of British Civil Servants, the Whitehall and Whitehall II studies,
      add to the understanding of social class differences in mortality and morbidity.
      Some of their results are presented to illustrate current concepts of social
      class differences in health. There is no evidence for an effect of health
      selection. The magnitude of social class differences vary for different causes of
      death, presumably as a sign of the effect of specific factors for specific
      disease. The observation that social class differences apply to most causes of
      death, however, suggest that factors like early life experience, difference in
      behaviour, material and psychosocial conditions act in an unspecific way.

PMID- 8256530
TI  - Preliminary results of primary screening for breast cancer with the Mama Program.
AB  - In 1972 a comprehensive BSE screening strategy for the early detection of breast
      cancer, the "Mama Program Screening" (MPS), was developed in Finland by the
      author on the initiative of women's organizations. The program consists of a)
      initial information about the facilities of the program and BSE-performance, b)
      prospective surveillance of the BSE-behaviour of complying women, who use a
      specially designed Mama calendar for regular notes on their BSE behaviour and c)
      a pre-organized system for women with self-identified anomalies in the breasts to
      self-refer to physicians in public health care. From 1973 to 1975 an MPS project
      was carried out in Finland with 56,000 exposed women. Compliance to BSE
      performance of once a month increased from 2% prior to the enrollment to 55%, and
      resulted in 2% of self-referrers. In the compliers, mortality from breast cancer
      was reduced overall by 29%, the screening being effective in all age groups, also
      in those under 50 years. The MPS was easy and inexpensive to implement in
      existing public health care systems with the information material developed for
      the study and with physicians in PHC facilities.

PMID- 8256531
TI  - Mammographic screening for breast cancer: background of a pilot program in the
      Canton of Vaud.
AB  - For several years now, substantial efforts have been devoted to the development
      and the implementation of a screening program for breast cancer in the Canton of
      Vaud. A four-year pilot phase is now starting, involving two regional hospitals
      with their catchment areas; women over 50 and under 70 years old will be invited
      to participate in the program. A double view mammography will be made, with a
      double reading made by the hospital radiologists; a third reading will be made in
      case of discrepancy between the two first radiologists. Patients classified as
      positive for screening (e.g., with a suspect radiological image) will be referred
      to their practitioner for further diagnosis and treatment. The medical and public
      health background of this program is discussed, more specifically the reasons for
      developing a screening program, the choice of mammography rather than other
      tools, and the need to implement screening as an organized program.

PMID- 8256532
TI  - Breast cancer screening: should it be introduced and how?
AB  - This brief discussion of the papers by Gastrin and Paccaud is looking at
      differences in the results of different study types. Introducing screening means
      changing unsystematic to systematic screening: only the latter has been shown to
      be effective. The comparison between randomized trials, and follow-up of
      acceptors only, suggests that the non-acceptors have much higher risks.
      Programmes should therefore concentrate on trying to reach non-acceptors. The
      combination of mammographic screening and self-examination in a randomized trial
      could add to the existing evidence.

PMID- 8256533
TI  - Reported disease and psychological well-being in Swiss adults.
AB  - In Switzerland, and in many other countries as well, the distribution of
      morbidity and perceived health in the general population and their determining
      factors have not been systematically studied so far. This article reports on
      exploratory study of prevalence of two complex health indicators, long-standing
      disease (Disease) and psychological well-being (Well-being) and of their
      environmental, person-specific and behavioural determinants. Data from a health
      survey conducted in five cantons and three language regions as part of the Swiss
      Intercantonal Health Indicators Project were used. Whereas distributions of
      prevalence of Disease according to gender, age, level of education and place of
      living confirm results of other studies, unexpected prevalence patterns were
      found for Well-being, especially with regard to gender differences. Multivariate
      analyses by general linear models (independent sub-samples of the study
      population were used to develop and validate models) showed different sets of
      environmental, person-specific and behavioural factors to explain inter
      individual differences of Disease and Well-being, both in the total validation
      sample and in sub-samples of women and men. The results are discussed with regard
      to implications for socioepidemiological health research.

PMID- 8256534
TI  - Socio-economic factors and mortality in Switzerland.
AB  - This review paper is concerned with the topic of mortality differences by socio
      economic group in Switzerland. After a short introduction to the topic and the
      pitfalls associated with it, the paper reviews work done in the course of a ten
      year programme investigating socio-economic mortality differentials in
      Switzerland. This programme was carried out by a working group at the Department
      of Social and Preventive Medicine of the University of Berne. The paper reviews
      methodological difficulties and pitfalls and relates the Swiss results to
      findings from other countries including England and Wales and Sweden. The
      disadvantages of socially isolated groups such as children of single women are
      shown. The relatively high mortality of groups under economic pressure, such as
      skilled manual workers in Switzerland, is demonstrated. The Swiss situation is
      interesting in that skilled manual workers have a higher mortality than the
      unskilled and semi-skilled groups. It is concluded that this is not an artifact
      but may be due to the fact that only Swiss workers were investigated and that
      Switzerland has a large proportion of foreign workers, especially in the less
      skilled groups. In addition, some results of an investigation of cancer mortality
      by occupation are reported too. Apart from some occupation-specific findings,
      there are some interesting cross-references to socio-economic differential
      mortality.

PMID- 8256535
TI  - WHO launches a new method to study adolescents' sexual behaviour.

PMID- 8256536
TI  - [Computed tomography in the diagnosis of intervertebral disk hernias].
AB  - Computed tomography (CT) was conducted in 75 patients with discogenic
      radiculitis. In 15 patients the study was carried out without intensified
      contrasting of the spinal cord meningeal spaces (native CT), in 60 with
      contrasting of the meningeal spaces with air (42 patients) or Omnipaque (18
      patients). The CT was analysed at the level of the bony and articular segments of
      the spinal canal. Deformity of the dural sac of the spinal cord was the most
      frequent sign of Schmorl's body. It was encountered in 96.2% of verified cases.
      CT is one of the methods for establishing the diagnosis of Schmorl's body.

PMID- 8256537
TI  - [Magnetic resonance tomography in the diagnosis of tumor processes in the area of
      the cerebellopontile angle].
AB  - The paper provides the results of magnetic resonance tomographic examination of
      patients with acoustic neurinoma, and shows that the method can be used in the
      defining the site of a focus, its size, and relations of the tumor with adjacent
      tissues. The paper also outlines the image structure of the tumor in relation to
      scanning techniques and gives magnetic resonance criteria for differential
      diagnosis of tumor processes in the region of the cerebellopontine angle. It is
      concluded that magnetic resonance tomography is of high informative value in the
      diagnosis of extra-axial tumors of the posterior cranial fossa.

PMID- 8256538
TI  - [The terminology of hydrocephalus following craniocerebral trauma].

PMID- 8256539
TI  - [The diagnosis and surgical treatment of posttraumatic hydrocephalus].
AB  - Posttraumatic hydrocephalus is an active progressive process of excessive
      accumulation of cerebrospinal fluid due to liquorodynamic disturbances following
      cerebrocranial injury. In addition to clinical assessments, it is necessary to
      use special diagnostic techniques to define indications for bypass surgeries
      which are an effective therapy for progressive posttraumatic hydrocephalus.

PMID- 8256540
TI  - [Internal hydrocephalus and basal liquorrhea (radionuclide data)].
AB  - The paper shows the value of radionuclide cysternomyelography in the diagnosis of
      internal hydrocephalus concurrent with basal liquorrhea. The authors examined
      1522 patients of whom 105 were found to have the pathology, this yielded
      radionuclide differential diagnostic criteria for this nosological entity. They
      proposed new technological conditions for enhancing its diagnostic value.

PMID- 8256541
TI  - [The treatment of hydrocephalus by ventriculojugular shunting].
AB  - A total of 43 patients with hydrocephalus of various etiology were examined.
      Ventriculojugulostomy was performed in 20 patients, its modification in 23.
      Bypass surgery was made on the internal jugular vein in 9 patients, on the common
      facial vein in 9 and on the external jugular vein in 5. There was an improvement
      in 43 patients in the immediate postoperative period, which was followed by
      regression of global brain symptoms and cessation of hydrocephalus progression.
      Long-term results are known in 32 patients who were discharged having a well
      functioning drainage valvular system. The follow-ups lasted from 6 months to 17
      years.

PMID- 8256542
TI  - [Epileptic seizures after cerebrospinal fluid shunting operations].
AB  - The paper analyzes one of the complication of spinal fluid bypass surgeries, i.e.
      epileptoid seizures. It is suggested that a significant role in the occurrence of
      seizures is played by irritation of the brain with an implantable drainage
      system, namely with the thickened drainage portion plunged into the brain at the
      junction of a pump and a ventricular catheter. The study provides evidence for
      the value of the presence of pathology risk for seizures which occurs after
      anastomosis implantation. This risk appears as EEG epileptoid activity even in
      the absence of clinical manifestations. Infectious complications and poor
      anastomosis drainage function are shown to be essential for the implantable
      anastomosis to provoke the seizures. The authors give recommendations to prevent
      epileptoid seizures following bypass surgeries and treat them if they occur,
      which allows this complication to be effectively combatted.

PMID- 8256543
TI  - [Spinal cord hernias and hydrocephalus].

PMID- 8256544
TI  - [Pathology of the cerebrospinal fluid tract after subarachnoid hemorrhages (the x
      ray and radiological aspect)].
AB  - The authors examined the semiotics of hydrocephalus occurring after
      subarachnoidal hemorrhages (SAH) from arterial aneurysms and arteriovenous
      malformations to provide pathogenetic evidence for surgical or conservative
      hydrocephalus. The spinal fluid tract was examined in 44 patients after SAH by
      computed tomography and radionuclide cysternomyelography using 99mTc. Variability
      was found in the radiological semiotics of open internal hydrocephalus.
      Radiological studies revealed frequently open internal hydrocephalus in patients
      with arterial aneurysms and arteriovenous malformations without subarachnoidal
      hemorrhages. The radiological semiotics of open hydrocephalus after SAH
      determines both morphological changes of the spinal fluid tract and
      liquorodynamic disturbances.

PMID- 8256545
TI  - [Hydrocephalus in ruptured aneurysm of the cerebral vessels].

PMID- 8256546
TI  - [Mobile x-ray computed tomography in the examination of neurosurgical patients].

PMID- 8256547
TI  - [Experience in using the new nonionic x-ray contrast medium Ultravist in
      neuroroentgenology].

PMID- 8256548
TI  - [Microvascular decompression in facial hemispasm].
AB  - Microvascular decompression in facial hemispasm is an operation rather
      infrequently performed in the CIS, while patients with facial hemispasms are
      great in number. The author obtained satisfactory results of the surgical
      intervention. Of special interest is the site of compression of the nervous root
      where the surgical intervention should be made.

PMID- 8256549
TI  - [The use of short-latency auditory evoked potentials in the diagnosis of acoustic
      neurinomas].
AB  - The short-latent acoustic evoked potentials in patients with unilateral
      neurosensory hypoacusis due to the tumor of the acoustic nerve or other etiology
      were recorded. It was found that the patients had no potential in the diseased
      area in monaural sound stimulation, but binaural sound stimulation enabled these
      potentials to be recorded. With this, the short-latent acoustic evoked potentials
      in patients with verified neurinoma showed a reduction in the third wave to the
      point of its disappearance. Those in patients whose neurosensory hypoacusis were
      unassociated with the development of neoplasms in the area of the acoustic nerve
      involve the third wave whose magnitude did not differ from that recorded in the
      examinees with otologically normal hearing. The authors propose to measure the
      third wave of the short-latent acoustic evoked potential recorded in binaural
      sound stimulation as a possible screening of persons at a high risk for neurinoma
      among patients with unilateral neurosensory hypoacusis.

PMID- 8256550
TI  - [24th Annual meeting of the Austrian Internal Medicine Association. 1993.
      Abstracts].

PMID- 8256551
TI  - Multiple sclerosis in the Faroe Islands. 5. The occurrence of the fourth epidemic
      as validation of transmission.
AB  - Based on 32 cases with clinical onset 1943-73, we previously described the
      occurrence of clinical neurologic multiple sclerosis (CNMS) on the Faroe Islands
      as constituting three consecutive epidemics, with 20, 9, and 3 cases
      respectively. As of 1991 there were seven additional cases of CNMS with clinical
      onset 1984-1989 constituting the fourth epidemic, as well as three more members
      of epidemic III. We have proposed that CNMS is the rare late result of infection
      with PMSA (the primary multiple sclerosis affection), a state requiring some two
      years of exposure from age 11+ for acquisition by Faroese, and that PMSA was
      first transmitted during World War II by affected but asymptomatic British troops
      to Faroese residents; part of this (F1) cohort of affected asymptomatic Faroese
      transmitted PMSA to the next (F2) cohort comprising Faroese reaching age 11 in
      the interval when that F1 subset was present, and the F2 cohort similarly
      transmitted PMSA to the third (F3) cohort. Cases of CNMS defining epidemic I-III
      were members of the respective F1-F3 cohorts. The existence of epidemic IV within
      the F4 cohort of Faroese may be taken as validation of our transmission models
      and of our theses as to the nature of multiple sclerosis.

PMID- 8256552
TI  - Increased generation of superoxide radicals in the blood of MS patients.
AB  - Increased generation of superoxide radical (O2-) in the blood stimulated with
      phorbol myristate acetate (PMA) has been found in multiple sclerosis (MS)
      patients. All the subjects studied were non-smokers and received the same
      hospital diet. In the MS group treated with prednisone superoxide radical
      generation was lower than in untreated patients, but was still above the level of
      O2- generation in controls. Plasma lipid peroxidation products, measured as
      thiobarbituric-reactive substances, were slightly elevated in both prednisone
      treated and non-treated MS patients in comparison with controls. Erythrocyte
      superoxide dismutase activity (SOD) was at the same level in MS and control
      groups. These results suggest that increased generation of reactive oxygen
      species may occur in MS patients during acute relapse. This phenomenon may be
      involved in the pathomechanism of demyelinating disorders.

PMID- 8256553
TI  - Cerebrospinal fluid IgG profiles and multiple sclerosis in Japan.
AB  - We analyzed the cerebrospinal fluid (CSF) IgG profiles of 46 Japanese patients
      with relapsing and remitting types of multiple sclerosis (MS). There were 12, 13
      and 21 patients, with inactive, active and both clinical conditions,
      respectively. The values for IgG, IgG/Alb ratio, IgG index and IgG synthesis rate
      were significantly higher during active than during inactive stages, but the
      patients with high values for these IgG profiles during active stages tend to
      also have high values during inactive stages. None of 33 (0%) and 2 of 34
      patients (5.9%) exhibited abnormal IgG levels, 3 (9.1%) and 8 (23.5%) an abnormal
      IgG/Alb ratio, 9 (27.3%) and 18 (52.9%) an abnormal IgG index, and 5 (15.2%) and
      14 (41.2%) an abnormal IgG synthesis rate, during inactive and active stages,
      respectively. Some of HLA antigen frequencies were significantly different
      between the patients with and without abnormal CNS IgG profiles. Increased CSF
      IgG was of lesser diagnostic value for MS in Japan, and seemed to be a function
      of immunogenetics rather than clinical activity.

PMID- 8256554
TI  - Anticardiolipin antibodies in Japanese patients with multiple sclerosis.
AB  - We evaluated circulating anticardiolipin antibodies (aCL) in 38 Japanese patients
      who fulfilled the criteria of clinically definite multiple sclerosis (MS), using
      a newly developed EIA system with aCL-cofactor. Two of 38 patients (5.3%) had a
      aCL-cofactor-dependent positive serology, and differences compared with findings
      in controls were statistically significant. The 2 aCL-positive patients had
      similar clinical features with acute transverse myelopathy (ATM), optic
      neuropathy (OPN), normal cranial MRI and negative oligoclonal IgG bands (OCBs) in
      the cerebrospinal fluid (CSF). Among the 38 patients, 3 had ATM, OPN, normal
      cranial MRI and negative OCBs, hence, in a significant number of the patients
      (2/3; 67%) with these distinctive features, serology for aCL was positive.
      Therefore, they may have another condition associated with aCL, masquerading as
      MS. Serological testing for aCL with aCL-cofactor is recommended for the patients
      with clinical diagnosis of MS, especially for those showing OPN and ATM during
      the clinical course, and in Asian peoples where the incidence of ATM and OPN is
      relatively high among the patients with diagnosis of MS.

PMID- 8256555
TI  - Do endogenous retroviruses have etiological implications in inflammatory and
      degenerative nervous system diseases?
AB  - Vertebrates carry large numbers of endogenous retroviruses (ERVs) and related
      sequences in their genomes. These retroviral elements are inherited as Mendelian
      traits. Generally, ERVs are defective without the ability of being expressed as
      viral particles. However, ERV sequences often have a potential for expression of
      at least some proteins. So far, the possible biological significance of ERVs is
      not clear. Nonetheless, there are observations suggesting a connection between
      ERVs and various diseases. This is the case with murine lupus and a spinal cord
      disease of certain mouse strains. In the present review, we discuss possible
      mechanisms by which ERVs could contribute to the development of human
      degenerative and inflammatory nervous system diseases, including direct effects
      on nervous system cells and immune cells. Interactions between ERVs and
      infectious viruses are also discussed. Finally, we review a possible retroviral
      etiology of multiple sclerosis.

PMID- 8256556
TI  - Possible association of HTLV-I infection and dementia.
AB  - We report a Swedish patient with progressive dementia possibly associated with
      human T cell-lymphotropic virus type I (HTLV-I) infection. The clinical
      investigation revealed no typical sings of other neurological disorders. The
      patient was probably infected in East-Asia 35 years before onset of the disease.
      High titers of specific HTLV-I antibodies were detectable with solid-phase
      peptide ELISA in serum (1:1.600) and cerebrospinal fluid (CSF) (1:20), and the
      CSF/serum anti-HTLV-I antibody ratio indicated intrathecal HTLV-I antibody
      synthesis. Western blot for HTLV-I and polymerase chain reaction with primers
      selected for the HTLV-I pol gene were positive in both peripheral blood and
      cerebrospinal fluid. HTLV-I antigen was also demonstrated after in vitro co
      cultivation of mononuclear cells from peripheral blood. Thus, our findings
      indicate that HTLV-I infection also may be associated with dementia. In addition,
      this case report calls attention upon HTLV-I as a possible etiologic agent to
      neurological diseases in countries previously spared from the infection.

PMID- 8256557
TI  - Changes in red blood cells with valproate therapy.
AB  - Increase in the red blood cell mean corpuscular volume (MCV), and mean
      corpuscular haemoglobin (MCH) values in patients receiving Valproate as mono or
      polytherapy was noted. To investigate this situation 41 epileptic patients were
      studied on Valproate alone (Group 1) and 20 patients on Valproate added to
      another antiepileptic drug (AED), (Group 4), and compared with 19 patients on
      carbamazepine (CBZ) (Group 2) and 12 patients on phenytoin (PHT), (Group 3). The
      results showed significant rise in MCV values in Groups 1 and 4. The peripheral
      blood smear and other tests including reticulocyte counts of the patients with
      abnormal values ruled out macrocytic anemias. We postulate a generalized effect
      which is the result of alteration in erythrocyte membrane phospholipids.

PMID- 8256558
TI  - Temperature effects on nerve conduction studies in patients with carpal tunnel
      syndrome.
AB  - This study was done to evaluate the effect of rising temperature on nerve
      conduction parameters in 22 patients with carpal tunnel syndrome (CTS). We wanted
      to find out whether diseased nerves responded to temperature rise in a different
      manner from normal controls. For this purpose a group of 20 healthy individuals
      were also tested. With rising temperature motor nerve conduction velocities
      increased, whereas latencies, amplitudes and duration of the compound muscle
      action potential decreased in both groups. These changes were not statistically
      significant between the two groups. Sensory nerve conduction parameters yielded
      basically similar findings except for a significantly smaller reduction in
      amplitude of the compound nerve action potential (CNAP) in the CTS group (p <
      0.005). We conclude that there is a different response in the sensory CNAP
      amplitude between normal and CTS groups, but the same nerve conduction correction
      formulae for temperature can be used in CTS patients as in normal individuals in
      the event of low skin temperature.

PMID- 8256559
TI  - An improved sedimentation technique for the cytologic preparation of
      cerebrospinal fluid cells.
AB  - The conventional CSF cell preparation methods suffer from a poor cell recovery
      rate (mean rates of 10-50% with the sedimentation techniques, which makes it
      unlikely, that the cell sampling on the slide is representative) or from
      suboptimal cell visualization (filter techniques). An improved sedimentation
      technique is described with a mean recovery rate of 80% and excellent cell
      visualization.

PMID- 8256560
TI  - Low frequency of post-lumbar puncture headache in demented patients.
AB  - The frequency of post-lumbar puncture headache (PLPH) was registered
      prospectively in 395 consecutive demented patients at a dementia diagnostic unit.
      The incidence of PLPH was low, occurring in only 8 patients (2.0%), the severity
      was mild, and the duration was less than 2 days in all cases but one. The reasons
      for this low frequency of PLPH in patients with dementia disorders may include
      disease- and/or age-related low pain sensitivity, rigid dural fibres and
      arteriosclerotic vessels, and large CSF space due to cerebral atrophy. Analysis
      of CSF is essential to identify secondary causes of dementia, preferentially
      chronic infections. The low frequency and severity of PLPH found in the present
      study shows that, with low risk of complications, lumbar puncture can be included
      in the routine clinical examination of demented patients.

PMID- 8256561
TI  - Arnold-Chiari malformation associated with sleep apnea and central dysregulation
      of arterial pressure.
AB  - The natural history of symptomatic adult type I Arnold-Chiari (ACM1) malformation
      is variable. Patients with this condition frequently develop corticospinal and
      sensory deficits, together with cerebellar signs and lower cranial nerve palsies
      in various combinations. In the present report we describe a patient with ACM1 in
      whom sleep apnea together with disturbances in the central regulation of arterial
      pressure were a major component of the symptomatology. These paroxysmal blood
      pressure changes has not been previously reported. The decompression of our
      patient's medulla, which contains the primary respiratory centers and
      baroreceptors, resulted in a marked improvement and indicate that the origin may
      have been on a central basis.

PMID- 8256562
TI  - Palatal myoclonus and opioid peptides.
AB  - We report a patient who presented palatal myoclonus (PM) after anoxic brain
      damage that was completely abolished by the administration of opioid agonists.
      This suggests the involvement of peptide systems in the development of PM.

PMID- 8256563
TI  - Efficacy of methylprednisolone administration in a case of continuous abnormal
      muscle activity syndrome.
AB  - We report a 20-year-old woman with continuous abnormal muscle activity syndrome
      in which pharmacological blockade of different sites of the motor unit
      demonstrates a peripheral nerve origin for the abnormal muscle activity. The case
      showed no markers of autoimmune disease. A rapid recovery after high dose i.v.
      methylprednisolone was observed supporting the hypothesis of an autoimmune
      pathogenesis.

PMID- 8256564
TI  - Rapid detection of cytomegalovirus structures in cerebrospinal fluid and brain
      biopsies by polymerase chain reaction.
AB  - The joint application of stereotactic brain biopsy and DNA amplification methods,
      like the polymerase chain reaction (PCR) are diagnostic purposes that allows in
      approximately 24 h to clarify the viral etiology of central nervous system
      infections. We demonstrate PCR results from the brain biopsy of an HIV-1 patient
      with two cerebral lesions. Beside the neuropathological diagnosis of a B-cell non
      Hodgkin lymphoma the experimental results are indicative of active transcription
      of cytomegalovirus (CMV) in cerebral tissue. The markedly higher amount of CMV
      specific RNA found in the biopsy specimens and CSF suggest the presence of an
      active infection with viral replication. CT-guided stereotactic brain biopsies
      followed by PCR fulfill the demands of a clinician, namely to get the results as
      fast as possible to initiate adequate treatment.

PMID- 8256565
TI  - Prevalence of MS in south Estonia. Evidence of a new border of the Fennoscandian
      focus.
AB  - A population-based study of MS was carried out in South Estonia in 1988-1989.
      Cases were identified from the Tartu University Hospital archives where all MS
      cases in South Estonia are diagnosed, from all neurologists and nursing homes of
      the region, and from the local Multiple Sclerosis Society. The prevalence in
      South Estonia is 51 per 100,000, for native Estonians 55, for Russians 29, for
      other nationalities 42 per 100,000. The prevalence rate in different counties was
      demonstrated as low as 31 per 100,000 in the County of Tartu, to 72 per 100,000
      in Polva County; 55% of patients have retired because of their handicap and only
      2 patients (1%) were living in nursing homes.

PMID- 8256566
TI  - Organic solvents and multiple sclerosis: a case-control study.
AB  - A case-control study of multiple sclerosis (MS) has been carried out in western
      Norway. The study included 93% of the patients who had clinical onset of MS in
      the county of Hordaland during the years 1976-86 (N = 155) and 200 controls,
      marginally matched for age, sex and residence. There was no statistically
      significant difference between MS patients and controls with regard to exposure
      to organic solvents, exposure to the combination organic solvents and welding or
      to organic solvents and other chemical compounds.

PMID- 8256567
TI  - Peroneal muscular atrophy with parkinsonism, ptosis, and congenital strabismus.
AB  - Peroneal muscular atrophy (PMA) may be occasionally associated with other
      neurodegenerative features including parkinsonism. We report the association of
      PMA of neuronal type with parkinsonism, ptosis and congenital strabismus in a 62
      year-old Sicilian woman. The complete syndrome was present only in the proband,
      but variously combined features were present in ten other family members over
      four generations, with likely autosomal dominant inheritance. Although a similar
      syndrome of PMA, ptosis, parkinsonism and dementia was already reported, this
      family showed a previously undescribed combination of features in view of the
      presence of congenital strabismus.

PMID- 8256568
TI  - Causes of morbidity and mortality, with special reference to surgical
      complications, after early aneurysm operation: a prospective, one-year study from
      neurosurgical units in Sweden.
AB  - In the present prospective study, 6.93 of Sweden's 8.59 million inhabitants (81%)
      were covered by the five participating centres. All patients with verified
      aneurysmal SAH admitted between June 1, 1989 and May 31, 1990, were enrolled.
      Basically, all participating centres have the same management protocol for SAH
      victims, including ultra-early referral to a neurosurgical unit, followed by pan
      angiography and surgery as early as logistically possible. In this presentation,
      145 patients who preoperatively were in Hunt & Hess Grades I-III and who
      underwent surgery for a supratentorial aneurysm within 72 h after the bleed, are
      evaluated. Eighty-one % (117 patients) made a good recovery. The morbidity was
      12% (17 patients) and the mortality 7% (11 patients). The most common cause of
      unfavorable outcome was surgical complications, which accounted for 8% of the
      total series (12 patients). A subanalysis of these cases did reveal a positive
      correlation to higher age and more severe SAH on CAT scan.

PMID- 8256569
TI  - Cavernous angiomatosis of the central nervous system: usefulness of screening the
      family.
AB  - A 23-year-old woman presented with cerebellar hemorrhage from a cavernous angioma
      (CA). A history of spinal hemorrhage and a supratentorial calcified lesion on CT
      and MRI suggested cavernous angiomatosis of the CNS. Familial investigation in 20
      relatives revealed 4 additional patients with symptomatic CA and one person with
      asymptomatic CA. In the symptomatic patients, CA had not been recognized as the
      cause of their neurologic symptoms prior to our investigation. The number of CA
      lesions in asymptomatic relatives was low. This study shows that, when a patient
      with cavernous angiomatosis of the CNS is encountered, systematic clinical and
      MRI investigations in other family members with a history or symptoms of
      neurologic disorder should be carried out.

PMID- 8256570
TI  - Capsular infarcts: location, size and etiology of pure motor hemiparesis,
      sensorimotor stroke and ataxic hemiparesis.
AB  - We investigated the types of syndrome, location, size and presumed causes of 72
      patients with acute capsular lacunar infarction. Clinical syndromes were
      classified into pure motor hemiparesis (PM), sensorimotor stroke (SM) and ataxic
      hemiparesis (AH). Lesion sizes of AH were significantly smaller than those of PM
      (p < 0.01) or SM (p < 0.01). When the lesion volume was classified into two
      groups, > or = 1 ml and < 1 ml, the large volume group had more frequent
      cardioembolic sources than the small volume group (41% and 18% respectively, p <
      0.05). In AH patients no cardioembolic sources could be detected. Significant
      carotid stenosis was found in only 4% of patients. Patients with anterior
      choroidal artery territory infarction had infrequent cardioembolic sources (7%).
      The results suggest that the lesion size varies with clinical syndrome and some
      etiological trends are seen in the volume and the location of lesions.

PMID- 8256572
TI  - A clinically oriented approach to smooth pursuit eye movement quantitative
      evaluation.
AB  - The electrooculographic technique was used to record smooth pursuit eye movements
      in 71 healthy subjects homogeneously distributed within an age range between the
      2nd and the 6th decades. The target moved at constant velocity (triangular ramps)
      and 9 different target velocities (V), from 10 deg/s to 50 deg/s were considered
      and presented according to pseudorandom sequence. Ad hoc software suppressed
      catch-up saccades so that a pursuit index (PI) value was computed for each ramp
      taking into account only the smooth pursuit tracking modality. It was
      demonstrated that the relationship between V and PI could be described by the
      linear model PI = a + b * V. Pursuit index was proved to be influenced by the age
      of subject (decade factor in the analysis of variance), since an almost linear
      increase in b values yields a reduction of pursuit index values. The method was
      tested in 22 multiple sclerosis patients and an association was found between the
      occurrence of cerebellar signs and the reduction of a value.

PMID- 8256571
TI  - AT-877, a Ca2+ antagonist, fails to reduce infarct size following rat middle
      cerebral artery occlusion.
AB  - We investigated the effects of AT-877, a Ca2+ antagonist, on rat middle-cerebral
      artery occlusion. All rats had 6-h ischemia, and treated animals received either
      3 or 10 mg/kg AT-877 s.c. just after the occlusion. Control animals received an
      equal volume of the vehicle. Prior to sacrifice, significant changes in the
      decrease of blood pressure and the increase of plasma glucose were observed in
      the treated rats. Although the infarct size tended to decrease, this decrease was
      not significant. Only when the blood pressure- or plasma glucose-matched
      subgroups were compared, the infarct volume decreased significantly in the drug
      treated animals. Thus, AT-877 failed to reduce ischemic brain damage unless the
      blood pressure or plasma glucose were controlled.

PMID- 8256573
TI  - Diagnosis of alcohol-related neurological diseases by analysis of carbohydrate
      deficient transferrin in serum.
AB  - Analysis of carbohydrate-deficient transferrin (CDT) in serum has been shown to
      be a good marker of current regular alcohol consumption at levels that are
      potentially harmful both to the liver and the nervous system. In this study CDT
      was analyzed by anion exchange chromatography and the results were evaluated in
      134 consecutively examined patients with neurological symptoms of possible or
      probable alcohol-related etiology. A total of 22% of the patients were regarded
      as current alcohol abusers and 93% of them had elevated CDT values. The majority
      of these cases suffered from diseases such as epilepsy, neuropathies, cerebral
      atrophy/dementia and cerebellopathy. Most of them were still in a socially
      functioning condition. Low alcohol consuming patients and abstaining patients
      with a previous history of alcohol abuse had CDT levels within the normal range.
      The results demonstrated that determination of CDT is a valuable tool in the
      diagnosis of alcohol-related neurological disorders provided that its biological
      turnover is taken into account.

PMID- 8256574
TI  - Effect of barbiturate on epileptiform activity: comparison between intravenous
      and oral administration. Sphenoidal, zygomatic and temporal recordings.
AB  - The present study was performed in order to compare: 1) the differences between
      oral and intravenous barbiturate on interictal epileptiform activity (sharp-waves
      and spikes) in the EEG, and 2) interictal epileptiform activity in the sphenoidal
      electrode compared to the temporal and zygomatic electrodes (an electrode placed
      at the cutaneous entry of the sphenoidal electrode) during intravenous
      barbiturate administration in patients with epilepsy. Two procedures were
      performed: 1) an oral pentobarbital sleep induction with 10-20 electrode
      placement including a zygomatic electrode, and 2) an intravenous thiopental sleep
      induction with the same electrode placement including a sphenoidal electrode.
      Thirty eight patients with complex partial seizures were included. During the
      oral pentobarbital procedure 34 of 38 (90%) patients showed interictal
      epileptiform activity compared with 22 of 38 (55%) patients during the
      intravenous thiopental procedure (p < 0.005). A interictal epileptiform focus was
      observed in 33 (87%) patients in the oral procedure and in 19 (50%) patients in
      the intravenous procedure (p < 0.01). Interictal epileptiform activity recorded
      in the sphenoidal electrode was also recorded in the zygomatic electrode. Except
      from two patients a good correlation was observed between the zygomatic
      electrodes and the F7/F8 electrodes. We conclude that administration of
      intravenous thiopental offers no advantage compared to the administration of oral
      pentobarbital as an activating procedure, and for standard interictal EEG
      recordings with sleep activation procedures, suitable places scalp electrodes
      including a zygomatic electrode with the use of oral pentobarbital may be
      sufficient.

PMID- 8256575
TI  - Focal myositis of the thigh: report of two cases.
AB  - Focal myositis is a benign inflammatory pseudotumor of skeletal muscle,
      presenting as a localized painful swelling within the soft tissue of an
      extremity. Histological examination reveals lymphocytic infiltration, scattered
      muscle fiber necrosis and regeneration, and interstitial fibrosis. Complete
      recovery follows surgical removal of the lesion. Two cases are presented of young
      active males with a localized painful swelling of the thigh. Clinical
      examination, standard laboratory tests, electromyography (EMG), magnetic
      resonance imaging (MRI) and surgical biopsies were performed. Surgical biopsies
      were formalin-fixed, paraffin-embedded and sections were stained with hematoxylin
      and eosin, van Gieson, modified Gomori trichrome and Mallory's method for iron.
      Clinical examination in both cases revealed an indolent lump in the quadriceps
      femoris muscle. Standard laboratory tests and electromyography were normal. MRI
      prior to surgery visualized the focal nature of the lesions. Histological
      examination of repeated surgical biopsies showed scattered muscle fiber necrosis,
      regeneration, and interstitial fibrosis but few lymphocytes. Both patients
      recovered after surgical removal of the lesion. Two years after surgery there was
      no recurrence of the lesions and repeated EMGs were normal.

PMID- 8256576
TI  - Electrophysiological and immunogenetic findings in recurrent monosymptomatic-type
      hypersomnia: a study of two unrelated Italian cases.
AB  - MSLT and immunogenetic findings in two unrelated Italian subjects with recurrent
      monosymptomatic hypersomnia are reported. In both patients MSLT documented a
      markedly increased daytime sleep propensity during the attacks without augmented
      REM sleep pressure. Both patients share the same HLA haplotype (HLA-DR1, DQ1)
      which has been found in Kleine-Levin syndrome. This makes these subtypes of
      recurrent hypersomnia indistinguishable one from the other, under the
      immunogenetic profile, but permits differentiation from narcolepsy which is HLA
      DR2, DQ1 closely linked.

PMID- 8256577
TI  - Cerebral cysticercosis in Norway.
AB  - Neurocysticercosis has been rare in Scandinavia. Due to immigration from and
      travels to endemic areas, we expect the number of such patients to increase. We
      here report the first four patients from Norway with diagnosed
      neurocysticercosis. Three are immigrants; one is of Norwegian heritage and was
      probably infested during short trips to other European countries.

PMID- 8256578
TI  - Nervous system involvement in systemic lupus erythematosus, Sjogren syndrome and
      scleroderma.
AB  - INTRODUCTION: The purpose of this study was to determine, whether there are any
      differences in the occurrence of nervous system involvement in different systemic
      rheumatic diseases. The further aim of the present study was to identify and
      distinguish primary involvement of the nervous system by these diseases and
      involvement that may be secondary to confounding factors. MATERIAL AND METHODS:
      The patient population consisted of 122 patients with a connective tissue disease
      (42 with systemic lupus erythematosus (SLE), 48 with Sjogren's syndrome and 32
      with scleroderma). The methods included neurological examination and standard
      electrophysiological tests. RESULTS: At least one neurological defect was
      diagnosed in 69% of SLE patients, in 71% of Sjogren's syndrome patients and in
      66% of scleroderma patients. Secondary factors might have contributed to the
      pathogenesis of neurological symptoms and signs in up to 25-34% of events.
      CONCLUSION: No significant differences were noted in the occurrence of
      neurological events in patients with SLE, Sjogren's syndrome and scleroderma. The
      necessity to differentiate between neurological phenomena directly attributed to
      the systemic rheumatic disease and those which are totally unrelated or secondary
      events resulting indirectly from involvement of other organ systems is
      emphasized.

PMID- 8256579
TI  - Aseptic meningoencephalitis in primary Sjogren's syndrome. Response to
      plasmapheresis and absence of CNS vasculitis at autopsy.
AB  - It has been suggested that cerebral vasculitis is the pathogenetic mechanism of
      the central nervous system manifestations of primary Sjogren's syndrome. We
      present a fatal case of aseptic meningoencephalitis in an 18-year-old woman with
      primary Sjogren's syndrome in whom there was no evidence of cerebral vasculitis
      at autopsy. On two occasions her condition improved markedly following
      plasmapheresis.

PMID- 8256580
TI  - In situ hybridization of myoglobin mRNA: results on the skeletal muscles of
      normal subjects and patients with neuromuscular diseases.
AB  - The intracellular localization of myoglobin(Mb) mRNA in the skeletal muscles of
      normal subjects and patients with Duchenne muscular dystrophy(DMD) or amyotrophic
      lateral sclerosis(ALS) was examined by in situ hybridization using a biotin
      labeled cDNA probe. In cross sections of normal muscles, Mb mRNA signals were
      demonstrated to be diffusely distributed as granular reaction products throughout
      the sarcoplasm, and in longitudinal sections the products were observed
      preferentially on the A-band. In DMD or ALS muscles, the distribution of granular
      mRNA signals showed some similarities with that in normal muscles, although
      degenerated fibers revealed a heterogenous distribution of the signals. In DMD
      muscles, the optical density(OD) of stained signal was higher in non-atrophic
      fibers and lower in atrophic fibers than in normal muscles. In ALS muscles, the
      OD was lower than in normal muscles. These results suggest that Mb mRNA is
      distributed preferentially on the A-band of the muscle fibers, and that in
      diseased muscle fibers Mb synthesis is affected by pathological changes.

PMID- 8256581
TI  - Ultrastructural observations on neuronal lipofuscin (age pigment) and dense
      bodies induced by a proteinase inhibitor, leupeptin, in rat hippocampus.
AB  - The ultrastructure of lipofuscin (age pigment) and dense bodies induced by
      intraventricular administration of leupeptin, a cysteine proteinase inhibitor,
      were investigated in the neurons of rat hippocampal dentate gyrus. Four-day
      treatment with leupeptin (0.5 mg/day) rapidly caused a considerable accumulation
      of intracytoplasmic dense bodies and swelling of neuronal processes. We
      demonstrated, as inner structures of the pigments, that penta-laminar structure
      with a thickness of 12-13 nm and finely granular matrix were exactly common to
      the leupeptin-induced dense bodies and lipofuscin granules. Furthermore, the
      transitional stages from lysosomes into the dense granules were observed in the
      neurons of the leupeptin-treated rats. On the other hand, some morphological
      differences between the leupeptin-induced dense bodies and lipofuscin granules
      have been shown: (1) distribution in different cell types, (2) intracytoplasmic
      location, (3) tendencies to associate with vacuoles, and (4) electron density.
      The present findings suggested that the decline of the lysosomal protein
      degradation could play a role in lipofuscinogenesis, especially in the genesis of
      their electron-dense portion, but some other mechanisms might participate in the
      formation and accumulation of lipofuscin with aging.

PMID- 8256582
TI  - Recovery of protein synthesis in tolerance-induced hippocampal CA1 neurons after
      transient forebrain ischemia.
AB  - Protein synthesis at various recirculation times after 5-min transient forebrain
      ischemia was evaluated in gerbil hippocampal CA1 pyramidal neurons that had
      acquired tolerance to delayed-type ischemic injury. Evaluation was performed by
      observing polyribosomes under electron microscopy, and by [14C]leucine
      autoradiography. Hippocampal CA1 pyramidal neurons in the gerbils acquired stable
      and reproducible tolerance to delayed-type ischemic injury subsequent to a 5-min
      ischemia by pretreatment that consisted of loading two 2-min ischemic periods at
      a 1-day interval, followed by 48 h of recirculation. During the early phase
      following the 5-min ischemia, polyribosomal disaggregation, loss of dendritic
      microtubules, and significant suppression of radiolabeled leucine incorporation
      were observed in the tolerance-induced CA1 neurons as well as in the non
      tolerance-induced neurons. While these findings persisted in the non-tolerance
      induced neurons throughout the duration of the experiment, most of the tolerance
      induced neurons demonstrated reaggregation of cytosomal ribosomes, increase in
      the number of dendritic microtubules, and restoration of impaired amino acid
      incorporation 24 h after the ischemia. These findings suggest that recovery of
      protein synthesis during the early post ischemic phase is essential for CA1
      neuron survival after ischemic injury.

PMID- 8256583
TI  - Immunohistochemical study of microglia in the Creutzfeldt-Jakob diseased brain.
AB  - Immunohistochemical techniques have been used to investigate microglial reaction
      in Creutzfeldt-Jakob diseased (CJD) brains. Autopsy cases of six patients with
      CJD and age-matched controls were studied. Formalin-fixed, paraffin-embedded
      brain tissue samples were stained with antibodies against major
      histocompatibility complex (MHC) class II antigen (Ag), leukocyte common antigen
      (LCA), CDw75, CD68 and glial fibrillary acidic protein. Of the patients with CJD,
      two with a subacute spongiform encephalopathic type and short-survival periods
      after onset of the disease showed an increased number of reactive microglia
      labeled with anti-MHC class II Ag or LCA in the affected cerebral cortex. In
      advanced cases of the panencephalopathic type of CJD, in which both cerebral
      atrophy and astrocytosis were marked, the increase of reactive microglia was
      small. Some vacuoles developing in the neuropil of the CJD patients were
      surrounded by MHC class II Ag- or LCA-immunoreactive microglial cells. The number
      of ramified microglia in the affected lesions was decreased, although their
      number in the hippocampus was not affected. These results indicate that microglia
      can frequently be involved in the process of CJD and may be activated at the
      early stage of the disease.

PMID- 8256584
TI  - Stabilization of c-myc protein in human glioma cells.
AB  - The regulation of c-myc protein, product of c-myc/genes, was studied in four
      glioma cell lines by Northern blot, pulse-chase dot blot, immunoblot and
      immunoprecipitation analyses. Northern blot analysis revealed no overexpression
      of c-myc transcript, and pulse-chase dot blot analysis showed normal turnover
      rate of c-myc transcript, suggestive of no evidence of aberrant regulation of c
      myc at post-transcriptional level. The synthesis levels of c-myc protein were
      shown by immunoprecipitation and closely associated with the c-myc transcript
      levels demonstrated by Northern blot, suggestive of no evidence of aberrant
      translational control of c-myc, whereas they were dissociated from the
      accumulation levels of c-myc protein shown by immunoblot, suggestive of an
      evidence of aberrant regulation of c-myc at post-translational level. The mean
      (+/- standard deviation) half-lives of c-myc protein in four glioma cell lines
      were calculated from the pulse-chase immunoprecipitation analysis, and being 98
      +/- 8 to 143 +/- 11 min, were about four- to sixfold longer than normal. In
      surgical specimens, the immunostain of c-myc protein was not found in normal
      astrocytes but localized heterogenously in nuclei of reactive astrocytes and
      glioma cells, and increased in stained cell number in proportion to malignancy.
      Although this study was limited to four glioma cell lines, it suggests that the c
      myc protein in glioma cells may be accumulated due to its prolonged half-life
      contributing to an uncontrolled proliferation.

PMID- 8256585
TI  - Proteins immunologically related to erythrocyte anion transporter band 3 are
      altered in brain areas affected by Alzheimer's disease.
AB  - Proteins immunologically related to the human erythrocyte anion transporter band
      3 are present in neurons of the human neocortex and hippocampus.
      Immunocytochemical studies show increased band 3 immunoreactivity in neurons in
      the brains of patients with Alzheimer's disease. Immunoblot studies show the
      presence of band 3-like molecules in brain membrane fractions, and suggest
      changes in expression and/or processing of band 3-like molecules in Alzheimer's
      disease-affected regions. We postulate that alterations in membrane-bound, band 3
      like molecules may reflect termination of neuronal lifespan in Alzheimer's
      disease.

PMID- 8256586
TI  - Comparison of integrin adhesion molecules expressed by primary brain lymphomas
      and nodal lymphomas.
AB  - The expression of 17 adhesion molecules was immunohistochemically examined in 5
      primary cerebral lymphomas (PCL) and in 5 histologically similar nodal lymphomas
      (NL) to evaluate their possible involvement in selective targeting of lymphoma
      cells to the brain. PCL and NL tumor cells showed very similar expression
      patterns: they were consistently positive for alpha 3, alpha 4 and beta 1
      integrin chains; negative for alpha 1, alpha 2, alpha 6, beta 3 and beta 4
      integrin chains; and heterogeneous for alpha 5, alpha L, alpha M, alpha X, beta 2
      and beta 7 integrin chains, as well as for intercellular adhesion molecule-1
      (ICAM-1) and the selectin LECAM-1. Loosely infiltrating PCL showed lower levels
      of the alpha L beta 2 integrin than compact cell clusters. Vessels stained for
      ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1). We conclude that the
      adhesion molecules implicated in the extravasation of non-neoplastic leukocytes
      (alpha 4 beta 1/VCAM-1 and alpha L beta 2/ICAM-1) are also expressed by both PCL
      and NL. The adhesion molecules examined are apparently not selective mediators of
      lymphoma cell homing to the brain, but at least alpha L beta 2 integrin might be
      related to the infiltration pattern of PCL within the brain parenchyma.

PMID- 8256587
TI  - Differential incorporation of processes derived from different classes of neurons
      into senile plaques in Alzheimer's disease.
AB  - The incorporation of neurites into amyloid deposits is an important step in the
      formation of senile plaques in Alzheimer's disease. It is unknown whether all
      neuronal types contribute neurites equally to plaques, or whether the processes
      of certain types are preferentially incorporated. We addressed this question by
      comparing the incorporation into neocortical plaques of neurites containing the
      widely distributed neuronal markers chromogranin A (CgA), parvalbumin (PV) and
      calbindin D-28K (CaBP) in relation to the number of neuronal perikarya expressing
      each of these substances in the neocortex. We found a consistent, statistically
      significant ranking, so that CgA-immunoreactive (ir) neurites were preferentially
      incorporated into plaques in comparison with PV-ir, and PV-ir were favoured over
      CaBP-ir neurites.

PMID- 8256588
TI  - Aluminum-induced alteration of surface anionic sites in cultured brain
      microvascular endothelial cells.
AB  - Confluent monolayers of cultured microvascular endothelial cells from goat brain
      were used as an in vitro model system of the blood-brain barrier to study the
      effect of aluminum on the anionic sites located on the cell surface. Four
      experimental groups were used: (1) untreated (control 1) cells growing in normal
      medium; (2) cells growing in a medium containing 50 microM maltol (control 2);
      (3) cells growing in a medium containing 50 microM aluminum maltolate; and (4)
      cells growing in a medium containing 6 microM cadmium chloride as a known
      cytotoxic substance. The cell cultures were exposed to the substances listed
      above for 4 days. The anionic sites were detected at the ultrastructural level
      with cationic colloidal gold and cationized ferritin in non-fixed and fixed cells
      (prefixation and postfixation procedures). In the applied experimental
      conditions, aluminum maltolate was found to affect the surface density of anionic
      sites, as manifested by their redistribution and segmental disappearance from the
      apical plasmalemma of the endothelial cells. These changes were more pronounced
      in the non-fixed than the fixed cells and are reversible. Most probably,
      aluminum, because of its unique properties as a cross-linker, facilitates the
      lateral migration of anionic sites induced by cationic probes. Whether these
      alterations contribute to in vivo aluminum-induced blood-brain barrier
      dysfunction requires further elucidation.

PMID- 8256589
TI  - Cerebrovascular permeability and brain edema after cortical photochemical
      infarcts in the rat.
AB  - The importance of protein extravasation for the development of vasogenic brain
      edema is still controversial. We, therefore, assessed the cerebrovascular
      permeability to serum proteins in relation to the development and resolution of
      brain edema in a photochemical cortical lesion in the rat. Cortical infarction
      was induced by in situ thrombosis using an argon laser beam aimed at the exposed
      parietal bone in animals given rose bengal i.v. The histology and the
      cerebrovascular permeability to serum proteins were scrutinized from 2 h to 3
      weeks after the insult. The presence of serum proteins was demonstrated by an
      immunoperoxidase technique. The cerebral water content was estimated by specific
      gravity measurements of the cortical tissue in a kerosene-monobromobenzene
      gradient column from 2 h to 7 days after infarction. The blood-brain barrier was
      permeable to proteins at 2 h following the insult and proteins spread into the
      medial and lateral tissue reaching a maximum at 24 h. The specific gravity did
      not deviate from control values at 2 h. After 8 h the specific gravity of the
      lesion decreased with smaller decreases in the immediately adjacent tissue. At 24
      h the changes in specific gravities reached a maximum in all regions except the
      immediately lateral area. The edema was generally worse in tissue medial to
      rather than lateral to the infarct. The degradation of serum proteins and the
      resolution of the brain edema followed the same time course with partial
      resolution of 72 h. By 1 week serum proteins and edema were confined to the
      central necrotic core. The results suggest a relationship between cerebrovascular
      permeability and cerebral edema in photochemical cortical infarction.

PMID- 8256590
TI  - Congenital muscular dystrophy. A study on the variability of morphological
      changes and dystrophin distribution in muscle biopsies.
AB  - Histomorphological and histochemical variability was studied in muscle specimens
      from 30 patients with congenital muscular dystrophy (CMD). We found involvement
      of the central nervous system in 8 patients (Fukuyama CMD, F-CMD), involvement of
      the brain and the eyes in 5 patients (muscle, eye and brain disease, MEB-D) and
      hypodense white matter on the CT scans of 2 patients with (sub)normal
      intelligence (occidental-type cerebromuscular dystrophy, O-CMD). No morphological
      hallmarks were found to differentiate these subgroups. Only fat cell infiltration
      was found to be increased with increasing age in 'pure' CMD (pure-CMD). The
      morphological data did not appear to be correlated with the clinical severity or
      type of dystrophy (pure-CMD, F-CMD, MEB-D and O-CMD). Immunohistochemistry with
      dystrophin, vimentin and desmin antibodies in 14 patients (6 pure-CMD, 5 F-CMD, 2
      MEB-D and 1 O-CMD) showed a normal expression pattern.

PMID- 8256591
TI  - Parkinson's disease with involvement of the parasympathetic ganglia.
AB  - We report the distribution of Lewy bodies in an 83-year-old man who was diagnosed
      histopathologically as having Parkinson's disease. Many sections were taken from
      the brain, spinal cord, spinal dorsal root ganglia and peripheral autonomic
      systems. In the central nervous system, Lewy bodies were present in many of the
      areas already reported by previous authors. In the peripheral nervous system,
      Lewy bodies were present in the sympathetic ganglia, enteric nervous system of
      the alimentary tract and the submandibular ganglion, which is a peripheral
      parasympathetic ganglion. The present case indicates that the peripheral
      parasympathetic ganglia are involved in the disease process of Parkinson's
      disease.

PMID- 8256593
TI  - Striatonigral degeneration with neurofibrillary tangles.
AB  - An autopsy was performed on a 48-year-old woman with clinical features of
      parkinsonism-plus syndrome with dominating akinesia. Neuropathological
      examination revealed striato-nigral degeneration (SND) and neurofibrillary
      tangles (NFT) characterizing progressive supranuclear palsy. Such an unusual
      combination of pathological findings may constitute a distinct clinico
      pathological entity, with akinesia as the main clinical symptom, and with a
      pathological substrate of SND and NFT. We suggest that such cases may establish a
      separate variant within multisystem atrophies syndromes.

PMID- 8256592
TI  - Inherited syndrome of infantile olivopontocerebellar atrophy, micronodular
      cirrhosis, and renal tubular microcysts: review of the literature and a report of
      an additional case.
AB  - An 8-month-old male infant who presented in the neonatal period with failure to
      thrive, bilateral pleural and pericardial effusions, and hepatic insufficiency
      characterized by elevated liver functions tests and hypoalbuminemia was found at
      autopsy to have an unusual combination of olivopontocerebellar atrophy (OPCA),
      micronodular cirrhosis, and renal tubular microcysts. Metabolic evaluation was
      significant only for elevated urine dicarboxylic acids. In the brain, sections
      from the cerebellum showed marked atrophy of folia most severe in the vermal and
      paravermal regions. In addition, mild neuronal loss was present in the basis
      pontis and inferior olivary nuclei accompanied by gliosis. Residual Purkinje
      cells in the cerebellar hemispheres exhibited greatly expanded and swollen
      arbors, which ultrastructurally were found to contain densely packed membranous
      cytoplasmic body-like inclusions that had the appearance of unwinding, lamellar
      coils. Review of the literature shows that this constellation of findings has
      been associated with carbohydrate-deficient transferrin. This biochemical marker
      along with the distinctive clinical presentation and pathological features
      clearly delineates a unique subset of OPCA.

PMID- 8256594
TI  - Glial fibrillary acidic protein-like immunoreactivity in the human fetal inner
      ear.
AB  - The distribution of glial fibrillary acidic protein (GFAP)-like immunoreactivity
      (IR) was analyzed in the human fetal inner ear using immunohistochemical
      techniques. In the 11-week-old human fetal cochlea, nerve fibers labelled with
      GFAP had reached the basilar membrane, but innervation stained by antisera
      against GFAP to the hair cells reached only as far as the basal coil. In the 11
      week-old human fetal vestibular organs, little GFAP-IR was present in the
      epithelia. In 14- and 15-week-old human fetal cochleae, rich immunoreactive
      neural networks were observed, including the inner spiral bundle. Many
      immunoreactive sites were found below inner hair cells in all coils. Outer spiral
      bundles in the first, second and third rows in the basal coil were labelled, but
      the outer spiral bundle in the third row in the apical coil was not stained by
      the antisera. In the macula utriculi, many heavily stained sites and a rich
      immunoreactive network in the sensory epithelium were labelled, while
      considerably fewer positive nerve fibers and sites were present in the sensory
      epithelia in the macula utriculi and cristae ampullares. These results suggest
      that GFAP-IR is a very useful marker of differentiation of Schwann cells in the
      peripheral nerve in the human inner ear.

PMID- 8256595
TI  - Tympanic membrane temperature in a patient with vertigo.
AB  - Tympanic membrane temperature (TMT) is greatly influenced by the internal carotid
      artery and the jugular vein. Average human brain temperature is influenced by the
      differences between the temperature of the internal carotid artery and of the
      jugular vein. TMT has been used extensively as an indicator of brain temperature.
      Tympanic membrane temperature was measured in six healthy men (control group) and
      one patient with vertigo. In the control group, TMT showed considerable circadian
      changes parallel to the core temperature. In the patient with vertigo, TMT varied
      widely after the attack of vertigo. These data can provide a basis for the
      understanding of vertigo attacks.

PMID- 8256596
TI  - Calcium mobilization in isolated cochlear spiral ganglion cells of the guinea
      pig.
AB  - Single cochlear spiral ganglion cells (SGCs) were isolated using enzymatic and
      mechanical techniques. Intracellular free calcium ion concentrations ([Ca2+]i) in
      the SGCs were measured using a digital imaging microscope and the Ca(2+)
      sensitive fluorescence dye fura-2. In the presence of the Ca2+ ionophore
      ionomycin (1 microM), there was an irreversible increase in [Ca2+]i.
      Depolarization by high K+ (150 mM) led to an increase in [Ca2+]i in SGCs, and
      this effect was reversible. The SGCs apparently possess voltage-gated calcium
      channels.

PMID- 8256597
TI  - Vagal and sympathetic nerve activities influenced by posterior cerebral
      circulation in rabbits.
AB  - Vagal and sympathetic nervous activities in the rabbit were recorded while
      vertebral blood flow was partially blocked by the injection of adenosine 5'
      diphosphate (ADP; platelet aggregator). When a small dose of ADP (0.2 mg/kg) was
      administered into a unilateral vertebral artery, sympathetic nerve (SN) activity
      increased, and its magnitude was inversely correlated with the extent of the
      decrease in blood pressure (BP). A larger dose (2 mg/kg) of ADP suppressed SN
      activity on the injected side, whereas the change was small on the non-injected
      side. Vagal nerve (VN) activity showed a monophasic excitatory response on both
      sides, although the change was larger on the injected than on the non-injected
      side. As a result, asymmetry in autonomic nerve activity was more distinct in SN
      than in VN. The present study demonstrated that asymmetry of autonomic nervous
      function can result from changes in blood flow in the cerebellum and brainstem.

PMID- 8256598
TI  - Immunohistochemical study of superoxide dismutase in the olfactory mucosa.
AB  - We used an anti-copper, zinc-superoxide dismutase (Cu,Zn-SOD) antibody in an
      immunohistochemical investigation of the distribution of SOD in the mouse
      olfactory mucosa. We also investigated differential staining with this antibody
      in comparison with an antibody specific to carnosine, a marker of mature
      olfactory cells. Mouse olfactory mucosa were immunostained with the ABC method
      with anti-SOD and anti-carnosine antibodies. When anti-SOD antibody was used, the
      sustentacular cells were positive in the olfactory region, whereas the olfactory
      cells were negative. In the respiratory region, the columnar epithelial cells
      were positive, whereas goblet cells were negative. The olfactory cells, olfactory
      vesicles and axons showed positive staining with anti-carnosine antibody, whereas
      the sustentacular and basal cells were negative.

PMID- 8256599
TI  - Nerve growth factor (NGF) and its receptor in rat olfactory epithelium.
AB  - Nerve Growth Factor (NGF) is a bioactive protein that plays an important role in
      the genesis, differentiation, growth, maintenance and aging of the central and
      peripheral nervous systems. The purpose of this study was to explore the
      significance of NGF in the turnover, regeneration and maintenance of the
      olfactory epithelium. We tried to detect NGF and NGF-receptor in the olfactory
      epithelium of young and mature rats with an immunohistochemical technique.
      Immunoreactivity to NGF and NGF-receptor was detected in all specimens of
      olfactory epithelium. Immunoreactivity to NGF was positive in the olfactory nerve
      cells, especially in the cytoplasm and dendrites, in the basal cell layer, and on
      fibers piercing the olfactory epithelium. Immunoreactivity to NGF-receptor was
      positive in the basal cell layer and on fibers piercing the olfactory epithelium.
      These results suggest that NGF plays a role in the maintenance of olfactory nerve
      cells, and in the differentiation from the basal cell to the mature olfactory
      nerve cell, in both the young and the mature rat. In addition, the differences in
      the density of immunoreactive cells between different parts of the olfactory
      epithelium support the concept of an active and a quiescent zone in olfactory
      epithelium turnover.

PMID- 8256600
TI  - Sympathetic nerve disturbance and fine structure of adrenergic nerve terminals in
      nasal mucosa after experimentally-induced nasal hypersensitivity.
AB  - Electron microscopic observations were used to study the relation between the
      adrenergic nerve terminal and the effector cell in the nasal mucosa of toluene
      diisocyanate-sensitized and non-sensitized guinea pigs. Adrenergic nerve
      terminals were abundantly distributed in the adventitia of arterioles, however,
      no synapse formation was observed in smooth muscle cells of the mesothelium,
      i.e., effector cells. Adrenergic nerve terminals were observed separated from
      smooth muscle cells of the mesothelium of the arteriole by distances of 1000 A
      3000 A. Neurotransmission by the sympathetic nerve in the nasal mucosa is assumed
      to be by diffusion of norepinephrine (NE) or by diffusive synaptic conduction.
      The mechanism of sympathetic hypofunction in the nasal mucosa in nasal
      hypersensitivity is assumed to be as follows: Released histamine directly
      stimulates H-1 receptors at the sympathetic nerve terminal, leading to the
      release of NE. Once released, NE is not readily reabsorbed, and is gradually
      depleted in the sympathetic nerve terminal, leading to hypofunction of the
      sympathetic nerve.

PMID- 8256601
TI  - The nasal cycle in patients with autonomic nervous disturbance.
AB  - The nasal cycle is thought to be controlled by the autonomic nervous system. In
      this study, we measured nasal airflow resistance in patients with lesions of the
      autonomic nerves that supply the nasal mucosa. We examined 20 patients with
      facial palsy as examples of parasympathetic disturbance, five with Horner's
      syndrome as examples of sympathetic disturbance, and one with acute
      pandysautonomia. The nasal cycle was observed in 13 patients with facial palsy
      and four patients with Horner's syndrome. The nasal cycle was also observed in
      one patient with acute pandysautonomia and disturbance of the sympathetic
      parasympathetic nerves. Our results indicate that disturbance of the
      parasympathetic and sympathetic nerves has little influence on the nasal cycle.

PMID- 8256602
TI  - Interleukin-5 preferentially recruits eosinophils from vessels in nasal mucosa.
AB  - Interleukin-5 (IL-5), initially described as possessing eosinophil
      differentiating and proliferating activity, has now been shown to exert its
      effects on mature eosinophils. To investigate the ability of recombinant human IL
      5 (rhIL-5) to cause the migration of eosinophils in the nasal mucosa in vivo, we
      compared the eosinophil counts in nasal mucosa without and after the nasal
      application of rhIL-5. In addition, the percentages of eosinophils in leukocytes
      within the vascular lumens in the nasal mucosa were counted to determine whether
      IL-5 recruited eosinophils from the vessels. The total number of eosinophils in
      both the epithelium and lamina propria, as well as the percentage of eosinophils
      in leukocytes within the lumens of vessels in the nasal mucosa after the
      application of IL-5, were higher than those in control nasal mucosa. Conversely,
      neither the number of neutrophils in the nasal mucosa nor the percentages of
      neutrophils in vessels differed between the two groups of nasal mucosa. The
      results strongly suggest that IL-5 preferentially recruits eosinophils from
      vessels into the lamina propria.

PMID- 8256603
TI  - Immunocytochemical localization of intermediate filaments in the guinea pig
      vestibular periphery with special reference to their alteration after ototoxic
      drug administration.
AB  - The present study examined the immunocytochemical localization of various
      intermediate filaments (IFs), 68 kDa, 160 kDa and 200 kDa neurofilament protein
      (NFP), cytokeratin (CK) 1, 8, 10 and 19, vimentin, and glial fibrillary acidic
      protein (GFAP) in the vestibular end-organs and ganglia of normal and
      streptomycin-treated guinea pigs. In normal animals, 68 kDa, 160 kDa and 200 kDa
      NFP were found in afferent nerve fibers and nerve terminals (probably nerve
      chalices). Fine nerve fibers (probably efferent and/or sympathetic nerve fibers)
      were also immunoreactive to NFP. In the vestibular ganglia, 68 kDa and 160 kDa
      NFP were predominantly distributed in larger cells, whereas 200 kDa NFP was also
      found in some small ganglion cells. Cytokeratin 8 and 19 were located in
      supporting cells, transitional cells, dark cells of vestibular end-organs, and
      the epithelial cell lining of the membranous labyrinth. Vimentin was observed in
      the hair cells distributed in the central region of the end organs, supporting
      cells, most connective tissue cells, and Schwann cells of the vestibular
      ganglion. Although GFAP-like immunoreactivity was evident in glial cells of the
      proximal vestibular nerve, no immunoreactivity was detected in the distal portion
      of the vestibular nerve, vestibular ganglion, or vestibular end-organs. These
      highly distinct staining patterns of IFs indicated that they may play different
      roles in the different cell types, and that they may serve as a specific marker
      for each cell type. In streptomycin-treated guinea pigs, immunoreactivities for
      NFP and vimentin (found in the hair cells) decreased after treatment, whereas
      immunoreactivities for the other IFs were not affected.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8256604
TI  - Misdirected reinnervation in the feline intrinsic laryngeal muscles after long
      term denervation.
AB  - Nerve terminals which resembled the autonomic nerve varicosities were found at
      all neuromuscular junctions of the feline intrinsic laryngeal muscles after 21
      months of unilateral laryngeal paralysis. The structure of muscle fibers was
      preserved throughout this period, although there was no evidence of regeneration
      of transected recurrent laryngeal nerve. In the cricothyroid muscle, misdirected
      reinnervation was recognized in the different pathways from the other intrinsic
      laryngeal muscles.

PMID- 8256605
TI  - Immunohistochemical study and an electron microscopic observation of the nucleus
      of the optic tract in the rat.
AB  - In the present study, gamma aminobutyric acid (GABA)-positive cells and terminals
      were detected in the nucleus of the optic tract (NOT) in the rat. However, GABA
      positive cells in the NOT receiving projections directly from retinal ganglion
      cells could not be identified. To determine the role of GABA in the projection
      from the retinal ganglion cells to the NOT, we used electron microscopy to
      observe this nucleus of a rat in which one eyeball had been removed. In the nerve
      synapse binding region of the NOT on the side opposite to the enucleated eyeball,
      the symmetrical and asymmetrical types were recognized; the ratio between the two
      was the same as before the eyeball was enucleated. From these results, we
      conclude that the inhibitory axon terminals in the NOT do not have GABA activity.
      The GABA-positive cells seem to act indirectly as intrinsic interneurons, when
      processing or transmitting the information from the retina to the inferior
      olivary nucleus.

PMID- 8256606
TI  - Distribution of calcium binding proteins in sensory organs of the ear, nose and
      throat.
AB  - Distributions of spot-35 protein (S-35), calbindin (CaB), and parvalbumin (PaV),
      three types of calcium-binding protein, were examined immunohistochemically in
      sensory organs of the ear, nose and throat in guinea pigs and rats.
      Immunoreactivity of S-35 and CaB was found in the outer hair cells and in
      vestibular sensory cells situated at the top of the ampulla, and in some cells in
      the macula. Microvillar cells in the olfactory epithelium, periglomerular cells,
      and small numbers of cells in the mitral cell layer in the olfactory bulb reacted
      to anti-S-35 and anti-CaB antisera. In taste buds, most gustatory receptor cells
      reacted to anti-CaB, although a few reacted to anti-S-35 antiserum. Neuron-like
      cells in the upper respiratory tract reacted similarly to these antisera. No PaV
      immunoreactivity was found in any region. These results indicate that S-35 and
      CaB play important roles in the special kinds of mechanoreceptor and
      chemoreceptor cells found in the otolaryngeal area.

PMID- 8256607
TI  - Autonomic innervations in the middle ear and pharynx.
AB  - Autonomic innervations of the mucosa in the middle ear and pharynx were
      investigated by retrograde labelling of the autonomic ganglia with horseradish
      peroxidase (HRP). Of the sympathetic ganglia, the superior cervical ganglion
      (SCG), middle cervical ganglion (MCG) and stellate ganglion (StG) were examined,
      and of the parasympathetic ganglia, the pterygopalatine ganglion (PpG) and the
      otic ganglion (OtG) were examined. Sympathetic innervation of the middle ear
      mucosa was accomplished by fibers originating in the ipsilateral SCG, but not by
      those originating in the MSG or StG. Parasympathetic innervation was by fibers
      originating in the ipsilateral PpG, but not by those originating in the OtG. The
      epipharynx received sympathetic innervation from the ipsilateral SCG, but not
      from the MCG or StG. Its parasympathetic innervation was from the PpG
      bilaterally, but not from the OtG. Sympathetic innervation of the mesopharynx was
      supplied by the SCG, MCG and StG, but no parasympathetic supply came from the PpG
      or the OtG. Sympathetic innervation was bilateral, but predominantly from the
      ipsilateral side. The hypopharynx resembled the mesopharynx, but had more
      innervation from the MCG and StG.

PMID- 8256608
TI  - [Herpetic vestibular neuronitis: a hypothesis].
AB  - Abundant experimental research has shown the potentially damaging effects that
      the herpes simplex virus (HSV) may have on peripheral or central nervous
      pathways. Fifty subjects (ages 20-45) with labial herpes virus (HSV-1) and 15
      (ages 25-35) with genital herpes virus (HSV-2) were studied through recording
      spontaneous and optokinetic nystagmus (OKN) and using the eye-tracking-test (ETT)
      by means of electronystagmography (ENG). Recording was carried out during the
      first two days after vesicular eruption and seven days later, when cutaneous
      manifestations had disappeared. Thirty-five of the 50 subjects with HSV-1 showed
      spontaneous nystagmus, frequently with a vertical component, which in most cases
      had disappeared by the seventh control day. We recorded qualitative alterations
      of OKN as well as ETT in 19 patients while in 3 subjects only ETT was abnormal.
      All the subjects were normal on the seventh control day. At no time did any of
      the patients with HSV-2 show objective signs involving the peripheral or central
      vestibular system. Our research shows that HSV infection, especially HSV-1
      infection, determines subclinical alterations of the vestibular function,
      probably due to the involvement of the brainstem. Therefore the virus is to be
      taken into account in establishing the etiology of "unknown" vertigo.

PMID- 8256609
TI  - [The combined esthetic and functional treatment of microtia].
AB  - In the treatment of unilateral microtia, most authors give precedence to external
      reconstruction, neglecting a middle ear surgery. On the other hand, in bilateral
      microtia more importance is given to the functional component which has to be
      dealt with before a child begins his school career in order to facilitate optimal
      harmonious psychophysical development. One author in particular has been
      attempting to solve the problem in its entirety, for more than 20 years. In the
      last years, thanks to the close collaboration with otologists, results which
      confirm the existing hypothesis have been obtained. This was possible because
      plastic reconstruction was done before the functional procedure and also because
      of improvement in surgical techniques of the latter. Thus it appears that
      collaboration between both specialists is basically mandatory. Authors tend to
      aim for complete aesthetic and functional solution in bilateral microtia as well.
      However in these cases, external reconstruction has to performed before a child
      begins his school cancer.

PMID- 8256610
TI  - [Bronchoalveolar lavage (BAL) in the diagnosis of pulmonary infections in
      immunocompromised children].
AB  - The authors report their personal case records of broncho-alveolar lavage in
      immuno-compromised children. 22 children were observed from 1991 to 1992 at the
      E.N.T. Department of the Bambino Gesu Hospital, National Research Institute, in
      Rome. Flexible bronchoscopy is used under both local and general anesthesia
      without muscle relaxants. The epithelial lining fluid collection is greater than
      that obtained when muscle relaxation is used. For each patient 3 specimens are
      collected: for virological, bacteriological, mycological and immunological
      analysis. In 90% of the cases a correct etiological diagnosis of the pulmonary
      disease was possible. In 14 cases the diagnosis was possible even after a week
      from the beginning of the antibiotic therapy.

PMID- 8256611
TI  - [A cancer marker study in patients with neoplastic pathology of the neck and head
      area].
AB  - Specific markers able to detect either the presence of tumours or to identify the
      histological type of tumour are not currently available. Previous work yields an
      inconsistent picture of actual effectiveness of oncological markers, we therefore
      carried out a study on the cancer patients in our clinic. The present paper
      considered five markers (CEA, SCC, ca 19-9, TPA and Ferritin) and tested their
      effectiveness in diagnosing and following patients with head and neck neoplasias.
      The study was carried out on 102 patients, divided into three groups: 59 had been
      histologically diagnosed cancer but had not received any treatment (first group),
      the remaining 43 who had been treated (second group). We have also monitored the
      first group of no treated patients six months after therapy (third group). Our
      results suggest that while no significant conclusions may be drawn from SCC and
      CA 19-9, we found interesting results concerning Ferritin. Indeed Ferritin values
      increased by 22% in the first group, by 26% in the second one and by 19% in the
      third one. CEA and TPA values increased in non treated patients only by 22% and
      12% respectively while they did not alter in the treated ones and they altered by
      10.5% and by 10% respectively six months after therapy. Although our data are
      still preliminary and speculative and further evidence is needed, we can infer
      that the stage of the cancer and the positive markers appear to be concluded. The
      correlation is even stronger when all the cases are considered, without
      introducing the statistical and epidemiological variables.

PMID- 8256612
TI  - [Morbidity and the morphofunctional aspects of myocutaneous flaps used in the
      head and neck area].
AB  - The authors analysed the data obtained from their experiences in extensive head
      and neck resections as well as reconstructive treatments using myocutaneous
      flaps. They tried to evaluate the reconstructive approach in terms of morbidity
      and functional results. Sixty-nine patients, treated from January 90 to November
      92 for advances intra-oral cancer, were considered in this study. The
      reconstructive procedure in 68 cases was the pectoralis major myocutaneous flap
      while in 5 cases the trapezius flap was utilized. Even though the oncological
      results were poor, the functional ones were quite encouraging. In fact, the
      assessment of speech and swallowing was extremely satisfactory in 83% of the
      cases. The morbidity related to both flap procedures was low and the patients'
      life quality was good. Indeed, the use of a free flap offers additional
      advantages, without necessarily compromising safety of the reconstruction. Free
      flaps in general allow greater leeway in flap design and donor-site choice than
      pedicled flaps. Several reports have already demonstrated the versatility,
      usefulness and reliability of these flaps, especially in intra-oral
      reconstruction. The intricate nature of microsurgery and the expense of
      microsurgical equipment inhibit this kind surgery in many institutions around the
      world where the standard myocutaneous flaps would be a more practical procedure.
      In conclusion, even those patients with a poor prognosis may be considered
      potential candidates for demolitive and reconstructive treatment with which
      satisfactory results may be obtained.

PMID- 8256613
TI  - [The prognostic significance of the extralaryngeal microscopic extension of a T3
      glottic carcinoma].
AB  - Incidence of microscopic infiltration of the laryngeal framework, with or without
      extra-laryngeal extension, was studied retrospectively in a series of 63 patients
      treated surgically for glottic T3 carcinomas in order to establish prognostic
      values. The results of histopathological examination revealed neoplastic invasion
      of the fibro-cartilaginous skeleton in 46 of the patients examined and in half of
      these microscopic diffusion in peri-laryngeal tissue. As far as prognosis is
      concerned, there was a clear-cut correlation between a decrease in survival rates
      and a contemporaneous increase in the real extension of the neoplasia, even if
      microscopic. In fact the NED survival rate of confirmed T3 patients was 85% while
      in cases reclassified as pT4, it was 64% and 47% on the basis on the absence or
      presence of extra-laryngeal extension. With these observations it is possible to
      affirm that the major staging is also attributable to cases with initial
      infiltration of the "laryngeal framework" without an extensive extension toward
      peri-laryngeal tissue. As far as T recurrences are concerned, a high incidence of
      relapse of the neoplasia was observed principally in the cases with extra
      cartilaginous diffusion. This observation may have a predictive role and
      therefore direct post-surgery follow-up as well as eventual complementary
      treatment.

PMID- 8256614
TI  - [Pharyngeal cysts of branchial origin, a review of the literature and a clinical
      case report].
AB  - Nasal pharyngeal swellings are very often treated without a previous complete
      clinical examination of the patient and of the disease site. For this reason the
      recurrence rate of this pathology is quite high. The causes for this phenomenon
      are likely due to the benign aspect of the tumor and the easy approach to the
      pharynx. Leaving aside the therapeutical aspect, there are also multiple theories
      concerning the etiology of pharyngeal cyst based on epidemiological and
      histopathological observations. Branchiogenic origin very likely seems to be the
      cause of cystic swelling arising at the lateral side of the pharynx, between the
      Eustachian tube and the posterior tonsillar pillar. Examination of the case
      review collected from literature, revealed that diagnostic and therapeutical
      procedures performed by various authors seem to be very haphazard, ranging from
      simple physical examination and puncture draining to CT and/or MRI scanning and
      external trans-mandibular approach to the cyst. The authors describe one case of
      a subject with a pharyngeal branchial cyst, who had been previously undergone
      puncture drainage. The correct diagnosis was achieved through MRI and cytologic
      examination of the fluid aspirated from the cyst. With MRI it was possible to
      make a correct topo-diagnosis, which localized the position of the cyst in the
      left pharyngo-tonsillar recesses, medial to the pharyngeal constrictor muscles.
      MRI also confirmed the absence of fistulous ducts connected to the cyst. These
      clinical and laboratory data induced us to use an intra-oral approach to the
      cyst, which was removed by blunt dissection. Physical examination and MRI were
      repeated six months later and showed the complete removal of the cyst and the
      presence of a synechia between the upper part of the left posterior pillar and
      the pharyngeal wall. No further treatment was given because of the absence of
      symptoms. The authors stress the importance of less invasive surgery in the case
      of pharyngeal cyst possible after detailed monitoring of the disease site with
      modern computed tomography CT, MRI.

PMID- 8256615
TI  - [Rhinoplasty across the centuries].

PMID- 8256616
TI  - [The quantitative effects of competition on verbal intelligibility in the
      elderly].
AB  - The Speech Reception Threshold (SRT) was adaptively measured using sentences in
      two groups of subjects: young, normal-hearing subjects and elderly hearing
      impaired subjects with high frequency loss. SRT was recorded in quiet and in
      noisy conditions with competition consisting in "speech noise" and continuous
      discourse delivered at intensities between 11.4 and 98.6 dBA SPL. A significant
      difference was found between the groups in that elderly subjects had higher SRTs
      in noise than the young counterparts expressed as signal to noise (s/n) ratio.
      Moreover, at noise intensities typical of everyday life, the SRTs of the elderly
      is 6 and 11.4 dBs/n higher than normal-hearing subjects, with speech noise and
      discourse respectively as competition. Communicative strategies that enhance s/n
      ratio should be considered in order to overcome the heavy effects of hearing loss
      in the elderly.

PMID- 8256618
TI  - Screening for growth hormone deficiency using urinary growth hormone measurement.
AB  - The diagnostic approach in growth hormone deficiency (GHD) is complicated. Two or
      more provocative tests are essential for definitive diagnosis of GHD. However,
      such testing cannot be carried out routinely on all subjects with short stature
      because of the need for hospitalization and blood sampling. A simple screening
      method for GHD would be of great value. Human growth hormone (hGH) levels were
      measured in the early morning urine of 192 children aged 7-15 years with height
      2.0 s.d. below the mean for their ages. Sixty-eight subjects were selected
      because they showed a urinary hGH level < 10 ng/g creatinine. They were further
      examined in terms of bone age and plasma insulin-like growth factor (IGF-I)
      levels. In 30 subjects, the ratio of bone age: chronological age was < 0.8 and/or
      plasma IGF-I level was < 0.7 U/mL. Finally 24 of these subjects were examined
      with provocative tests and other endocrinological tests. Eleven subjects proved
      to have poor growth hormone secretion and one subject was diagnosed as having
      Turner syndrome. In conclusion, 11 patients with GHD were diagnosed from 192
      children with short stature using urinary hGH measurement as the first screening
      method. These findings suggests that urinary hGH measurement could be a useful
      and simple method for detecting GHD.

PMID- 8256617
TI  - Assessment of body composition measured by bioelectrical impedance in children.
AB  - Bioelectrical impedance methods have been found to be a valid and reliable way of
      estimating per cent body fat (%BF) in adults. We applied them to healthy children
      and compared them with conventional anthropometry methods. One thousand two
      hundred and sixteen children participated in this study. Impedance and skinfold
      thickness were measured, and %BF was estimated using these values. Bodyweight and
      height were measured, and per cent obesity (%OB) and body mass index (BMI) were
      obtained. The values of %BF by the bioelectrical impedance method (%BFi) were 8.6
      +/- 4.0% in the junior male group, 14.2 +/- 2.8% in the junior female group, 7.9
      +/- 4.7% in the senior male group and 16.1 +/- 2.9% in the senior female group.
      The %BFi correlated strongly with skinfold thickness, %OB and BMI. Thus %BFi
      correlated strongly with variables from conventional methods. It was concluded
      that it is a reliable way of assessing lipid storage in children.

PMID- 8256619
TI  - Relapses after termination of therapy of acute lymphoblastic leukemia in
      children.
AB  - In the past 16 years, 2004 children with acute lymphoblastic leukemia (ALL) have
      been treated in the Polish Pediatric Group centers. Eight hundred and eighty
      seven (44.3%) of these patients discontinued treatment after the first remission.
      Acute lymphoblastic leukemia relapse occurred in 180 patients (20.3%). This group
      was analyzed for the method of treatment and its influence on long-term survival,
      the time between cessation of treatment and relapse, the character and
      localization of relapse and later follow-up. It was shown that the patients with
      the best chance of a second remission are those with late testicular relapse. The
      most frequent and prognostically poor are bone marrow (BM) relapses which warrant
      intensive chemotherapy with BM transplantation. Patients with ALL relapse still
      have the possibility of a second remission and long-term survival.

PMID- 8256620
TI  - Virological and serological studies on poliomyelitis in Karachi, Pakistan. I.
      Outbreaks in 1990-91.
AB  - Between October 1989 and September 1991, 124 cases of poliomyelitis visited the
      Department of Paediatrics, Civil Hospital Karachi, Pakistan. The majority of them
      were between 6 months and 2 years of age and the epidemics occurred during the
      hot seasons. The dominant serotype was poliovirus type 1 during the epidemic
      season in 1990 and type 2 in 1991. All the polioviruses isolated from the
      patients were wild-type. Virological studies also disclosed that enteroviruses
      other than polioviruses were prevalent among healthy children as well as among
      diarrheal and polio patients. A serological survey to elucidate the serological
      efficacy of oral polio vaccine (OPV) showed that: (i) in 112 unimmunized
      children, after disappearance of transplacental maternal antibody during early
      infancy, antibody prevalence increased gradually and > 80% of the children were
      seropositive against all three types of polioviruses at 5 years of age; (ii) in
      201 children immunized with full doses of OPV in their infancy, the decrease in
      antibody titer during infancy was less and seroprevalence rose sharply
      afterwards: at 2 years of age, > 80% of them were seropositive against all three
      types of the virus. The rapid increase of seroprevalence might be the effect of
      OPV administration. However, the prevalence was lower than that in developed
      countries.

PMID- 8256621
TI  - Increased urinary excretion of human cytomegalovirus in children with malignancy:
      detection by polymerase chain reaction.
AB  - Human cytomegalovirus (HCMV) is one of the most important agents causing
      opportunistic infections in immunocompromised hosts. In this study, we examined
      the urinary excretion of HCMV in children with malignancy using polymerase chain
      reaction (PCR). Urine samples were collected from on-therapy, off-therapy
      patients with malignancy, and healthy controls. A simple DNA extraction method
      using glass powder was employed, and inhibitory effect of urine on PCR was
      prevented. For PCR, a pair of primers from the HCMV major immediate early gene
      sequence was used. Among patients who received intensive chemotherapy, 52.0% had
      urinary HCMV excretion after the chemotherapy course. In contrast, off-therapy
      patients and healthy controls showed a lower incidence of urinary HCMV excretion
      (20.4 and 8.7%, respectively). The incidence of HCMV urinary excretion in the on
      therapy group was significantly higher than healthy controls (P < 0.05). In the
      on-therapy group, the total white blood cell count of the virus excreters was
      lower than that of non-excreters. The incidence of HCMV excretion was high in on
      therapy patients. Most of the virus excreters were seropositive, so their viruria
      was thought to be caused by reactivation. Repeated monitoring of virus excretion
      by this rapid and simple method may be useful to detect HCMV infection early and
      to control it in such patients.

PMID- 8256622
TI  - Defective activity of Epstein-Barr virus (EBV) specific cytotoxic T lymphocytes
      in children with chronic active EBV infection and in their parents.
AB  - Antibodies of Epstein-Barr virus (EBV), EBV-specific cytotoxic T lymphocyte
      (EBVCTL) activity and the lymphocyte subset of CTL were examined in 13 Japanese
      children with chronic active EBV infection (CAEBV) and their parents (eight
      fathers and 10 mothers). Anti-virus-capsid antigen (VCA)-IgG antibody titers
      ranged from 1:640 to 1:5120 in the patients with CAEBV and from 1:40 to 1:640 in
      the parents. While anti-VCA-IgM antibody was detected in three patients, anti-VCA
      IgA antibody in five and anti-early-antigen (EA)-IgG antibody in 11, no antibody
      was detected in the parents except anti-EA antibody, which was positive in the
      mothers of cases 5 and 13 (1:10 and 1:40). Anti-EBV-associated nuclear antigen
      (EBNA) antibody was < or = 1:10 in six out of 13 patients with CAEBV and in 10
      out of 18 parents tested. Epstein-Barr virus activity was significantly lower (P
      < 0.005) both in the children with CAEBV and in their parents than in
      seropositive age-matched controls. Proportions of a CTL subset (CD8+ CD11-
      lymphocytes) in the patients with CAEBV were significantly higher (P < 0.005)
      than in controls, while those in the parents were at the same level as in
      controls. Defective EBVCTL activity and anti-EBNA-antibody responses were
      frequently observed both in children with CAEBV and in their parents, which may
      suggest that the abnormal immune response to EBV may be based on a familial
      disorder, though no familial involvement has been reported in Japanese children
      with CAEBV.

PMID- 8256623
TI  - Active immunization of children with leukemias and lymphomas against infection by
      hepatitis B virus.
AB  - Engerix B vaccine was administered to 54 children with leukemias and lymphomas
      aged from 2 to 15 years. In 36 cases chemotherapy was completely stopped, and 18
      cases were receiving maintenance treatment. Engerix B was given at 0, 1, 2 and 6
      months in a dose of 20 micrograms to children < 10 years, and 40 micrograms to
      older patients. The effectiveness of active immunization was demonstrated after
      complete therapy cessation in 88% of cases. The levels of antibodies determined 1
      year after primary vaccination remained high, and in most of the vaccinated
      children they were > 1000 mIU/mL. In children vaccinated in the course of
      maintenance treatment the levels of antibodies did not give sufficient protection
      against infection.

PMID- 8256624
TI  - Bone marrow transplantation for late infantile metachromatic leukodystrophy:
      pathogenic investigation for graft rejection.
AB  - A Japanese boy aged 2 years 11 months with late infantile metachromatic
      leukodystrophy underwent bone marrow transplantation (BMT) from his human
      leukocyte antigen (HLA) identical but mixed lymphocyte culture reactive father.
      Chimerism and increased arylsulfatase A activities of leukocytes had been
      observed with retarded progression of neurological deterioration during the first
      3 months post-BMT. Graft rejection gradually occurred and donor cells were almost
      completely eliminated from the patient at 1 year after BMT. The process of
      neurodegeneration progressed clinically and neuroradiologically. Three possible
      reasons for the pathogenesis of graft rejection are: (i) T cell depletion of
      donor marrow cells as graft-versus-host disease (GVHD) prophylaxis; (ii) a
      slightly weak conditioning regimen: and (iii) a small number of marrow cells
      transplanted. It is stressed that as BMT is still a preliminary therapy for
      metachromatic leukodystrophy indications, conditioning, and GVHD prophylaxis for
      BMT should be considered individually.

PMID- 8256625
TI  - Asymptomatic Becker muscular dystrophy: histological changes in biopsied muscles.
AB  - The histological changes observed in consecutive tests of biopsied muscles from
      an asymptomatic patient with Becker muscular dystrophy (BMD) are reported. The
      first biopsy showed active muscle necrosis and clustered regenerating fibers. The
      second biopsy revealed chronic myopathic changes mixed with neurogenic
      involvement. It is stressed that active myogenic changes observed in younger and
      asymptomatic BMD patients were followed by chronic myogenic or neurogenic change
      with age. Finally, we confirm the necessity of checking for dystrophin of
      abnormal size or reduced abundance by immunoblot analysis.

PMID- 8256626
TI  - The increase of yellow skin colour beyond that of serum bilirubin: a proposed
      indicator of risk for bilirubin encephalopathy in the newborn.
AB  - Forty-seven newborn infants with 1 min Apgar score < 7 were studied. On the third
      postnatal day the following measurements were made: yellow skin colour, serum
      bilirubin concentration, reserve albumin concentration and plasma pH. Given the
      bilirubin concentration and the regression curve between the yellow skin colour
      and the bilirubin concentration, delta-TcB was calculated as the difference
      between measured yellow skin colour and the expected yellow skin colour. There
      was a negative correlation between delta-TcB and Apgar score (P = 0.003), pH (P =
      0.026) and reserve albumin concentration (P = 0.045). Fourteen of the included
      newborns had central nervous system symptoms in the days just following birth. A
      tendency towards higher delta-TcB was noted in this group (P = 0.08). The results
      suggest that further study of delta-TcB determination as a tool in the assessment
      of the icteric newborn infant is justified.

PMID- 8256627
TI  - Stroke and meningitis in a case of SLE with anti-phospholipid antibodies.
AB  - Anti-phospholipid antibodies (aPL) are concerned with many central nervous system
      diseases in systemic lupus erythematosus (SLE). However, no report has described
      the relationship between aseptic meningitis and aPL in SLE. We report a case of
      SLE with aPL, presenting cerebral infarction and aseptic meningitis. A 14 year
      old female with SLE with aPL experienced cerebral infarction and recurrent
      aseptic meningitis. Combination therapy with steroids and aspirin improved the
      condition and prevented relapses. The aPL are associated with cerebral
      infarction, even in young patients with SLE. In addition, aPL may induce aseptic
      meningitis in SLE.

PMID- 8256628
TI  - Immunological aspects of juvenile rheumatoid arthritis.
AB  - This article reviews the evidence from recent studies on immunological
      abnormalities associated with pathophysiologic mechanisms operating in three
      clinical subtypes of juvenile rheumatoid arthritis (JRA) (polyarticular,
      pauciarticular and systemic). The main discussion is focused on three hallmarks
      of immunopathological studies. First, abnormalities in phenotype and function of
      lymphocytes from peripheral blood and inflamed synovium are discussed. The
      aberrations of lymphocytes are elucidated by T and B cells expressing phenotypic
      cell-markers such as CD20, CD21, CD4, CD8 and DR in association with different
      subtypes and disease activity. The functional imbalance and impairment of T and B
      cells are mainly observed by abnormal proliferation and/or in vitro Ig production
      in response to mitogens and alloantigens. Second, because the appearance of
      rheumatoid factors (RF) in serum indicates that the pathogenesis of JRA may be
      based on the autoimmune mechanism, the prevalence of RF including IgM, IgA and
      IgG isotype, hidden IgM RF and cross-reactive idiotype RF, and their
      characteristic properties are discussed. Moreover, specific auto-antibodies
      (antinuclear antibodies and others) for JRA are illustrated in this paper. Third,
      the production of various pro-inflammatory cytokines resulting in the release of
      tissue-damaging chemical mediators is also discussed. This may play a central
      role in the generation of systemic inflammation and joint involvement in JRA.

PMID- 8256629
TI  - A study of prognosis in 52 cases with juvenile rheumatoid arthritis.
AB  - The prognosis in 52 patients with juvenile rheumatoid arthritis (JRA) was
      studied. There were 35 cases of systemic onset, 12 of polyarticular onset and 5
      of pauciarticular onset. Thirteen systemic cases developed a polycyclic course
      with chronic polyarthritis. Many monocyclic JRA in systemic cases subsided within
      1 year. There were no instances of polyarticular cases or pauciarticular cases
      that shifted to other type. However, there were many cases with a long active
      polyarticular JRA and with remission at an early stage in the pauciarticular
      type. The stage and class were I or II in 90% of cases with a good prognosis for
      the joints, but there were some serious cases. Transient carditis or iritis which
      developed at an early stage subsided later. The intractable systemic cases had
      drug-induced complications. The cases with steroid-induced complications tended
      to be chronic. One death in a systemic case was caused by hepatic failure.

PMID- 8256630
TI  - Non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs in
      juvenile rheumatoid arthritis.
AB  - The preferred drugs for the initial treatment of juvenile rheumatoid arthritis
      (JRA) are salicylates or other non-steroidal anti-inflammatory drugs (NSAID) such
      as tolmetin or naproxen. If the disease activity does not respond adequately to
      the treatment, slow-acting anti-rheumatic drugs (SAARD) such as oral gold agents,
      low-dose D-penicillamine, or sulfasalazine should be given in addition to NSAID.
      If the systemic manifestations are severe, corticosteroid therapy may be
      commenced. Furthermore, if the joint destruction is progressive,
      immunosuppressants such as methotrexate would be selected as the third-line drugs
      of choice. The safety and efficacy of SAARD and immunosuppressants for the
      treatment of children with JRA, however, have not yet been confirmed, as the
      adverse effects such as bone marrow suppression, oncogenicity and mutagenicity
      are sometimes intense. Consequently, the strict indications for use and new
      therapeutic concepts for the management of JRA based on its pathogenesis are
      required.

PMID- 8256631
TI  - Quality of life and daily management of children with rheumatic disease.
AB  - Appropriate management of the daily life of patients with rheumatic diseases is
      an important part of therapy for favorable results and a high quality of life. At
      home, gymnastic exercise, night splints and appropriate fun activities will help
      to preserve the function of affected joints of patients with juvenile rheumatoid
      arthritis (JRA). Improvement of home fixtures according to patient disability
      will provide a higher quality of life for the patients. The patient should be
      helped to perform as many school activities as would normally be possible.
      Instructional charts for management of school life for patients with JRA and
      systemic lupus erythematosus is shown in this article. Cooperation with school
      personnel is also crucial to support the patient emotionally and physiologically.
      For the best long-term treatment and a good relationship between patient and
      physician, comprehensive management is essential. Not only physicians, but also
      psychiatrists, occupational therapists, physical therapists and social workers
      should be involved in the treatment of children with rheumatic diseases.

PMID- 8256633
TI  - Mixed connective tissue disease in childhood.
AB  - Since 1981, 21 children diagnosed with mixed connective tissue disease (MCTD)
      have been reported in detail in the literature in Japan. Overlapping clinical
      features and laboratory findings of these children were analyzed according to the
      established criteria of the Ministry of Health and Welfare, Japan. Mixed
      connective tissue disease in childhood typically begins with Raynaud's phenomenon
      preceded by several months or years with the appearance of other symptoms and
      signs including fever, arthralgia, myalgia, and/or progressive systemic sclerosis
      like skin manifestations. Serologically all the children with MCTD were positive
      for anti-ribonuclear protein (RNP) antibody with speckled-type antinuclear
      antibody. Hypergammaglobulinemia, positive rheumatoid factor, and
      normocomplementemia were characteristic. In general, prognosis is considered to
      be fairly good as opposed to systemic lupus erythematosus in childhood, but
      severe pericarditis/myocarditis or nephrotic syndrome can occur. Long-term follow
      up study and improved laboratory detection of anti-ribonucleoprotein antibodies
      will be necessary for further characterization of MCTD in childhood, and for the
      improvement of therapy.

PMID- 8256632
TI  - Current issues in Kawasaki disease.
AB  - The most important clinical aspect of Kawasaki disease is the cardiovascular
      problems. This article reports on the cardiovascular spectrum in acute Kawasaki
      disease, analysis of myocardial infarction and fatal cases, a follow-up study on
      the natural history of coronary artery lesions, long-term cardiovascular problems
      including premature atherosclerosis, problems in the adult cardiology and the
      treatment of acute Kawasaki disease. The etiology and pathogenesis of this
      disease are still unknown. Current hypotheses and leading studies on the etiology
      and the pathogenesis of Kawasaki disease are also reviewed.

PMID- 8256634
TI  - Current topics in childhood lupus nephritis.
AB  - Lupus nephritis is a major predictor of the prognosis of systemic lupus
      erythematosus (SLE). The present paper discusses lupus nephritis from clinical
      and immunopathological points of view. Although recent advances in diagnosis and
      treatment improve the prognosis of children with SLE, there remain many unsolved
      clinical problems. One of the current topics in the treatment for SLE is
      intermittent intravenous cyclophosphamide therapy which is effective even for the
      steroid-resistant patients with severe lupus nephritis, at least for short-term
      observation. Immunopathologically, the following issues are discussed: (i) The
      C5b-9 terminal complement complex plays an important role in the pathogenesis of
      lupus nephritis. The possible interaction of vitronectin and SP-40,40 is also
      mentioned; (ii) A semi-quantitative analysis of the charge barrier of the
      glomerular basement membrane reveals that the charge barrier dysfunction plays an
      important role in the pathogenesis of proteinuria in lupus nephritis. This study
      also demonstrates that the charge of immune deposits is important for the
      initiation of glomerular injury in lupus nephritis; (iii) It is demonstrated that
      the histopathological diversity of lupus nephritis is based on biological
      properties of nephritogenic auto-antibodies in murine lupus models.

PMID- 8256635
TI  - Excluding linkage between panic disorder and the gamma-aminobutyric acid beta 1
      receptor locus in five Icelandic pedigrees.
AB  - The GABAA receptor subunits are candidate genes for panic disorder because the
      receptor is the site of action for the anxiolytic effects of the benzodiazepines.
      We tested for linkage between a tetranucleotide repeat polymorphism at the GABAA
      beta 1 locus, located on chromosome 4p13-p12, and panic disorder defined by DSM
      III-R criteria in 5 Icelandic pedigrees. Both a narrow affection status (definite
      panic disorder and agoraphobia) and a broad one (including probable cases of
      these disorders) were tested. With the narrow definition, at a recombination
      fraction of 0.00, the lod scores in the 5 pedigrees ranged from -3.240 to +0.063,
      the total score across all 5 pedigrees being -8.299. With the broad definition at
      the same recombination fraction, the individual lod scores ranged from -2.614 to 
      0.489, with the total being -8.089. Thus, linkage between panic
      disorder/agoraphobia and the GABAA beta 1 locus in these pedigrees is exceedingly
      unlikely.

PMID- 8256636
TI  - Pathways to psychiatric care in Cantabria.
AB  - This article delineates the pathways taken in different health areas of Cantabria
      (Spain) by a series of newly referred patients to the mental health services and
      explores the influence of sociodemographic, medical and service-related factors
      on the delays in referral. The work forms part of an ongoing World Health
      Organization multicentre research programme aimed at exploring and optimizing the
      quality of mental health care in different centres of the world. We found that,
      in a rural health area, the majority of newly referred patients establish the
      first contact with the general practitioner and to a lesser extent with the
      hospital doctor and from there directly progress to the psychiatric services; in
      the urban health area there is a greater tendency to contact specialized medical
      and psychiatric services. Delays in these health areas are remarkably short and
      are comparable to the ones in other European centres. Our data also show that
      somatic symptoms are the main presenting problem both at the primary care and at
      the mental health level; and that, in general, psychotropic drug prescriptions
      are high both in hospital and in general medical settings, and that women were
      more often prescribed psychotropic medication than men.

PMID- 8256637
TI  - Emergence of depressive symptoms during treatment for panic disorder with
      specific 5-hydroxytryptophan reuptake inhibitors.
AB  - Selective serotonin reuptake inhibitors (SSRI) have been established as effective
      drugs in the treatment of depressive and anxiety disorders. However, there are
      also reports that they can induce depressive symptoms and suicidal thoughts in
      patients. Eighty of 230 patients who met the DSM-III-R criteria for panic
      disorder received, during the course of treatment, fluvoxamine (a selective
      serotonin reuptake inhibitor) at a dose level between 50-200 mg/day. The patients
      were clinically evaluated for a history of affective disorder and for the
      presence of affective symptoms before the treatment and for emergence of
      depressive symptoms during the treatment. Seven of the 80 patients (9%) developed
      symptoms of depression despite a good antianxiety response. Five of the 7
      patients received fluvoxamine as second choice after tricyclic antidepressants
      (TCA). These patients had no history of affective disorder, and no symptoms of
      depression were present before the treatment with fluvoxamine. The depressive
      symptoms abated after the fluvoxamine was discontinued and TCA or clonazepam was
      prescribed. The depressive symptoms reappeared when fluoxetine was administered.
      None of these 7 patients developed depressive symptoms while treated with TCA or
      clonazepam. Among the 150 patients treated with TCA and benzodiazepines, not a
      single case of depression was seen in patients without a previous history of
      depression. These results suggest a vulnerability among some of panic disorder
      patients to noradrenergic-serotonergic imbalance caused by SSRI, which has to be
      taken into clinical consideration.

PMID- 8256638
TI  - Cooperatives as a social enterprise in Italy: a place for social integration and
      rehabilitation.
AB  - This article analyses the history and development of an integrated cooperative
      established in 1981 in northern Italy. Integrated cooperatives, otherwise known
      as social enterprises, are among the most interesting activities developed in the
      area of social assistance and rehabilitation in recent years in Italy. In
      particular, they acquired relevance in the care of mentally disordered people by
      providing them with job opportunities, which is an important rehabilitative and
      integrative factor. The aim of social enterprises is two-fold. They have the
      economic goal of offering remunerative work just as any other commercial
      enterprise, as well as the social mandate of promoting the physical, social, and
      mental health of their members. A positive coexistence between market competition
      and rehabilitation is therefore constantly pursued. This research aimed at
      analysing the working and social experience of people employed by the cooperative
      during its 10-year life. The study was limited to those who had a social or
      health problem when entering the cooperative. The investigation was promoted by
      cooperative members, who felt the need to document their experience and to
      undertake initiatives towards evaluating the rehabilitative value of the social
      enterprise. The results show that cooperative members come from different
      marginalized areas of social and health distress, of which the two largest are
      social service users and psychiatric service users. There is a noticeable turn
      over rate, which underlines one function of the cooperative as being a
      transitional working context from which users can gain access to other more
      rewarding job opportunities in the labour market.

PMID- 8256639
TI  - Depression and the experience of psychological deficits in schizophrenia.
AB  - A study of the relationships between depression and the subjective experience of
      psychological deficits was carried out in a group of 50 schizophrenic patients
      selected from a population of long-term mentally ill patients. Experience of
      psychological deficits was associated with depression, and furthermore the
      temporal relationships between the phenomena supported the hypothesis that
      experience of psychological deficits is associated with vulnerability to
      depression in schizophrenia. In addition, the patients' self-reporting of
      depressed mood and negative cognitions was congruent with an observer's
      assessment of depression. These findings indicate that subjective experiences of
      deficits characteristic of the schizophrenic illness confer vulnerability to
      depression, but nonetheless the patients' experience of depression resembles that
      typical of depressed non-schizophrenic patients.

PMID- 8256640
TI  - The influence of premenstrual syndrome on ratings of anxiety in women with
      generalized anxiety disorder.
AB  - During the premenstrual and follicular phases of the menstrual cycle, 41 women
      who had generalized anxiety disorder (GAD) plus premenstrual syndrome (PMS) were
      assessed with psychiatric rating scales and compared with 21 GAD patients without
      PMS and 19 controls. The latter two groups were rated only once, in the typical
      open-ended manner. Symptoms during both phases of the menstrual cycle were more
      severe in the GAD + PMS patients than in the controls and were more severe during
      the premenstruum. For the GAD + PMS patients, ratings obtained in the typical
      open-ended manner were influenced by how patients felt during the premenstruum.
      Thus, the assessment of women with GAD + PMS may be complicated by cyclical
      fluctuations in symptom severity, and ratings obtained in the typical manner may
      be influenced disproportionately by how these patients feel premenstrually.

PMID- 8256641
TI  - The profile of C-reactive proteins in functional psychotic states in a cohort in
      Nigeria.
AB  - Based on the findings of previous work involving the measurement of 8 acute-phase
      proteins in 8 subjects receiving electroconvulsive therapy, we assayed the levels
      of C-reactive proteins (CRP) in 40 functional psychotic subjects, 37 of whom were
      consecutive admissions at the psychiatric ward. From 16 subjects, a second sample
      of blood for assay of CRP was collected 6 weeks after discharge from hospital,
      when the patients were no longer experiencing psychotic symptoms. The patients
      and controls were screened for tissue injury, inflammatory conditions and other
      diseases. We found that 14 (35%) of the psychiatric patients and only one (2%) of
      50 normal control subjects had detectable levels of CRP. At follow-up, none of
      the 7 patients in whom CRP had been earlier detectable had measurable levels of
      CRP in the non-psychotic state. The presence of CRP was not related to
      biochemical indexes of nutritional status (total proteins and albumin), nor did
      clinical variables such as type of psychosis, pacing in acutely disturbed
      patients, use of intramuscular injections or diet and drugs distinguish the two
      groups of patients. It is suggested that the presence of CRP in the psychotic
      state is probably a state-dependent expression of nonspecific humoral immune
      alteration in subjects in whom more specific tests could reveal some immune
      alteration.

PMID- 8256642
TI  - The relationship between mental health and drug use.
AB  - The aim was to examine the relationship between mental health and use of
      different kinds of drugs. The study was a cross-sectional survey of a total
      population aged 45-69 years, conducted in 2 municipalities in southwestern
      Finland. Altogether 1821 people (80% of those invited), 815 men and 1006 women,
      took part in the screening. The subjects were examined by a questionnaire mailed
      beforehand and checked in a personal interview. The questionnaire contained
      questions about the currently used drugs and Goldberg's questionnaire on mental
      health. Half of the people examined used prescribed drugs currently, more women
      used drugs than men, and the use of drugs increased with age. Mental symptoms
      measured with the Goldberg Index appeared in one fifth of the subjects, showing a
      slight increase with age. Men with mental symptoms showed a fourfold psychotropic
      drug use compared with the men without mental symptoms. The women with mental
      symptoms showed a threefold use of psychotropic drugs compared with the women
      without mental symptoms. Similar differences were found also in other drug
      groups, for example cardiac glycosides, other cardiovascular drugs, analgesics
      and drugs for respiratory and digestive organs. Persons with mental disorders
      showed a high tendency to drug use, also when those drugs had no direct
      attachment to the mental problem. Men seemed more liable to somatization of
      mental problems than women.

PMID- 8256643
TI  - Subclinical eating disorders in male athletes. A study of the low weight category
      in rowers and wrestlers.
AB  - This study investigated the possibility that male athletes who, owing to the
      rules of their sport, are pressured to maintain a low weight show an elevated
      prevalence of subclinical eating disorders. Twenty-five wrestlers and 59 rowers
      in the lower weight categories were investigated using the Eating Disorder
      Inventory (EDI). Fifty-two percent of the athletes reported the occurrence of
      binging. The EDI profiles of 11% of the athletes suggested the presence of a
      subclinical eating disorder. These figures are clearly elevated compared with the
      normal male population. Low-weight wrestlers and rowers should be considered a
      high-risk male population for subclinical eating disorders. These findings are
      comparable to high-risk groups consisting mainly of women (such as ballet and
      modelling students). The causal relationship between the specific sport and the
      development of a psychogenic eating disorder is discussed.

PMID- 8256644
TI  - Clinicians' information habits, patients' knowledge of diagnoses and etiological
      concepts in four different clinical samples.
AB  - A total of 230 psychiatric inpatients and their physicians in charge took part in
      semistandardized interviews. Patients suffering from schizophrenia received
      information less frequently and less comprehensively than other patients. The
      label of schizophrenia was often paraphrased or not communicated at all; patients
      knew their diagnosis less exactly than other subgroups. Asked to indicate the
      most important cause of their disorder, neurotics tended to name their living
      conditions (60%), and addicts preferred to blame themselves (73%). Only 26% of
      the patients with affective disorders or schizophrenia accepted the idea of their
      disorders as diseases in a medical sense, whereas the psychiatrists favored a
      biological concept in more than 90% of the cases. The findings stress the need to
      improve communication between patients and psychiatrists as regards information
      on illness and treatment.

PMID- 8256645
TI  - Characteristics of chronic outpatients with unipolar depression.
AB  - Among the long-term clinic attenders with unipolar depression, there are some who
      continue to visit the hospital after their affective symptoms have long abated.
      They constitute "new chronic" psychiatric outpatients and remain consumers of
      medical resources. We studied these patients' characteristics through a case
      control study with former patients who received treatment for the same diagnosis
      but are currently not under treatment and not depressed. The long-term clinic
      attenders tended to show fewer psychomotor symptoms and criteria symptoms than
      the control group. Although the groups were similar in terms of the severity of
      current depressive symptoms, the patients showed significantly poorer functioning
      in many areas of social adjustment. With regard to premorbid psychosocial
      variables, the chronic clinic attenders reported poorer friendship relationships
      during their adolescence, poorer premorbid global functioning and higher
      extraversion scores. These findings support the hypothesis that the social
      maladjustment of the chronic clinic attenders is not a sequela of their affective
      disorders but represents the patients' enduring characteristics.

PMID- 8256646
TI  - Mental illness and social integration among suicide attempters in Copenhagen.
      Comparison with the general population and a four-year follow-up study of 100
      patients.
AB  - In order to describe a population of suicide attempters in an affluent suburb of
      Copenhagen, 100 patients were interviewed, randomly chosen from a group of 246
      patients referred to psychiatric consultation after a suicide attempt. The group
      consisted of 71 women and 29 men. Single status, abuse, and previous suicide
      attempts occurred frequently as did suicide among first-degree relatives. The
      most frequent reason for a suicide attempt was conflict with partners. In
      comparison with the normal population in the same catchment area, the patients
      were alone and felt lonely, but no difference was found in the group's relation
      to the labor market. After a four-year follow-up period, 9 persons had died by
      suicide. Borderline personality disorder and affective psychosis, no employment,
      2 or more previous attempts, violent method and potential lethal attempt proved
      to be predictors of suicide later on. Alcohol and drug abuse, lack of social
      support and loneliness did not influence the risk.

PMID- 8256647
TI  - Daytime consumption of triazolam.
AB  - Six cases of daytime use of triazolam are reported. In all cases, daytime anxiety
      following the night-time use of this short-acting, high-potency hypnotic
      benzodiazepine led to the use of the drug during the day. Tolerance to the
      hypnotic and anxiolytic effects of the drug developed, as shown by a significant
      escalation of both the bedtime and daytime doses.

PMID- 8256648
TI  - Intoxication in manic patients following chaotic self-administration of lithium.
AB  - Intoxication is a serious complication of lithium therapy. Suicides attempted by
      depressive patients or excessive serum levels due to reduced renal elimination
      are typical causes of these intoxications. So far, lithium intoxications
      following excessive intake by patients with manic disorders have not been
      reported. We present 4 case histories of manic patients in whom the diagnosis of
      lithium intoxication was delayed, even though their affective disorders and
      medication were known. Lithium should be determined immediately on a routine
      basis in all patients who, on the basis of their history, are known to receive or
      who, considering the underlying mental illness, possibly receive lithium therapy.

PMID- 8256649
TI  - Treatment of winter depression in Norway. I. Short- and long-term effects of 1500
      lux white light for 6 days.
AB  - Patients with seasonal affective disorder (winter depression) from the Oslo area
      (at about 60 degrees N) recruited through mass media advertising were treated
      with 1500-lx white full-spectrum light for 2 h in the morning for 6 days. Their
      clinical state was assessed at baseline and 1, 3, 6, 10 and 14 weeks after
      commencement of treatment with an extended version of Montgomery-Asberg
      Depression Rating Scale (MADRS) and Clinical Global Impression. Forty patients
      (35 women, 5 men, age range 24 to 64 years) completed 1 week of light treatment.
      A subgroup of 9 patients received light in addition to ongoing drug treatment.
      The mean reduction in total extended MADRS score at week 1 was 48% in patients
      receiving only light and 56% in patients receiving light in addition to drugs. In
      spite of the low dose of light given, this is comparable to other reported
      results using light treatment for winter depression. In contrast to most other
      studies, however, the improvement at week 1 was maintained for the rest of the
      season in most patients. Only 5 patients were given another light treatment
      course, and another 5 were switched to drug treatment due to their unsatisfactory
      response to light treatment.

PMID- 8256650
TI  - Lithium augmentation in sertraline-resistant depression: a preliminary dose
      response study.
AB  - Eleven patients with DSM-III-R major depression who were treatment-resistant to
      sertraline were allocated for lithium augmentation therapy. In conjunction with
      their sertraline, 6 received lithium carbonate 400 mg at night and 5 received 800
      mg at night. A total of 7 patients responded within 1 week. The degree of
      response was not related to the serum lithium level. Patients with lithium levels
      as low as 0.3 mEq/l responded. No significant side effects were reported.

PMID- 8256651
TI  - Carisoprodol abuse: a report from India.
AB  - Carisoprodol, a centrally acting muscle relaxant, has recently been noticed to be
      abused. A series of 16 cases with carisoprodol abuse or dependence is described.
      Carisoprodol was started by the majority of patients as a substitute for opiates,
      although its independent distinct effects, similar to the features of hypomania,
      were recognized and described by most users. The drug is currently available
      freely over the counter and is a much cheaper substitute for the legally
      prohibited "harder" drugs. Unless awareness spreads and cautionary measures are
      taken, carisoprodol abuse might become a great menace in the near future.

PMID- 8256652
TI  - PCR detection of cytokines in normal human and pagetic osteoblast-like cells.
AB  - We investigated the expression of cytokine transcripts in osteoblast-like cells
      derived from explants of pagetic and normal bone. A reverse transcription-linked
      PCR was used that allowed the simultaneous analysis of a range of cytokines.
      Normal osteoblast-like cells were found to contain the transcripts for IL-1 beta,
      IL-6, and TGF-beta 1. For the first time we detected in bone cells the two other
      mammalian isoforms of TGF-beta, beta 2, and beta 3. Furthermore, we have also
      identified mRNA for IL-3 and the novel chemotactic factor, IL-8. Using this
      sensitive technique it was not possible to detect mRNA for IL-1 alpha, IL-2, IL
      4, IL-5, IL-7, TNF-alpha, or interferon-gamma. The human osteosarcoma cell line
      Saos-2 also showed a similar pattern of expression of these cytokines to primary
      osteoblast-like cells, with the exception that TNF-alpha was also identified.
      Cells isolated from pagetic bone showed essentially the same profile of cytokine
      expression as normal bone except that TNF-alpha was also detected in two of four
      samples. The cytokine profile of successive populations of cells harvested from
      one explant culture at 9, 22, and 57 days showed a consistent pattern of cytokine
      expression, demonstrating the phenotypic stability of the osteoblast-like cells
      in long-term cultures.

PMID- 8256654
TI  - Preliminary characterization of porcine bone marrow stromal cells: skeletogenic
      potential, colony-forming activity, and response to dexamethasone, transforming
      growth factor beta, and basic fibroblast growth factor.
AB  - Neonatal pig bone marrow stromal cells (PBMSC) were tested in vivo and in vitro
      to establish their use as a large-animal model for the study of skeletogenesis.
      When implanted in diffusion chambers in athymic mice for 6-8 weeks, both freshly
      isolated pig bone marrow and passage 2 PBMSC formed partially mineralized
      cartilage, bone-like material, and fibrous tissue. The cartilage showed
      metachromatic, perilacunar staining with toluidine blue and safronin O, alcian
      blue staining for chondroitin and keratan sulfate, and intense immunostaining for
      type II collagen. Osteocalcin was immunolocalized to the mineralized regions,
      consistent with the formation of bone. Alkaline phosphatase was primarily
      observed in cell layers at boundaries between tissue types. Unstimulated
      monolayer cultures of PBMSC produced type I but not type II collagen, responded
      to dexamethasone (10(-8) M) with a 1.7-fold increase in alkaline phosphatase
      activity, and were stimulated to divide by basic fibroblast growth factor (1.5
      fold; EC50 1 ng/ml). Transforming growth factor beta (TGF-beta) blocked both
      dexamethasone-induced alkaline phosphatase expression (EC50, 1 ng/ml of TGF-beta)
      and the mitogenic effects of bFGF (EC50 0.06 ng/ml of TGF-beta). When incubated
      for 10-14 days in medium containing dexamethasone, beta-glycerophosphate and
      ascorbate PBMSC formed mineralized nodules. Calcification occurred in the middle
      of the aggregates and was associated with intensely alkaline phosphatase positive
      cells and a dense type I collagen-rich matrix. PBMSC also displayed colony
      forming unit-fibroblastic activity, with approximately 1 in 80 of the plated
      cells formed colonies > 128 cells over 14-21 days. PBMSC therefore mimic the
      known activities of stromal cells from other species, including the human,
      suggesting that they are a valid model for skeletal research.

PMID- 8256653
TI  - Regulation of cytokine expression in osteoblasts by parathyroid hormone: rapid
      stimulation of interleukin-6 and leukemia inhibitory factor mRNA.
AB  - PTH and other hormones that stimulate resorption affect osteoclasts indirectly by
      modulating cytokine production by osteoblasts. However, the identity and role of
      the osteoblast-derived cytokines involved in this process are unclear. To examine
      which cytokines are regulated by PTH, we assessed cytokine mRNA levels in
      osteoblasts using the reverse transcription-polymerase chain reaction technique.
      Of the 16 cytokines we examined, unstimulated MC3T3-E1 osteoblastic cells
      expressed mRNA for interleukins 5, 6, and 7, macrophage and granulocyte
      macrophage colony-stimulating factors, transforming growth factor beta 1, and
      leukemia inhibitory factor. PTH specifically increased expression of interleukin
      6 (approximately 50-fold) and leukemia inhibitory factor (approximately 10-fold).
      Levels of both IL-6 and LIF mRNA peaked 30-60 minutes after addition of PTH and
      returned to baseline by 4-6 h. This rapid and transient mRNA response, which
      resembles that of immediate early genes, was also observed in primary rat
      osteoblasts. The transient mRNA response was accompanied by increased secretion
      of IL-6 protein. Lipopolysaccharide, another stimulator of resorption, increased
      mRNA levels of a group of cytokines that were not induced by PTH, namely
      interleukin-1 alpha, tumor necrosis factor alpha, and granulocyte-macrophage and
      granulocyte colony-stimulating factors. We conclude that osteoblasts produce
      complex networks of cytokines that (1) are regulated by bone-resorptive agents
      and (2) may be involved in controlling bone resorption.

PMID- 8256655
TI  - Effect of different amounts of sodium intake for 4 months on calcium metabolism
      in normal and oophorectomized rats.
AB  - The effects of different amounts of salt intake on urinary calcium and
      hydroxyproline (OHP) excretion were studied in oophorectomized (O) and sham
      operated (S) rats on normal calcium diet. Groups of O and S rats were given
      either tap water or 2, 6, or 18 g/liter of NaCl to drink. Urinary excretion of
      sodium, calcium, and OHP was monitored at 0, 2, and 4 months. Urinary excretion
      of calcium and OHP increased with increasing salt intake (P < 0.001 by ANOVA) in
      S and O groups. Oophorectomy did not have any additional effect on calcium or OHP
      excretion. We conclude that increased salt intake causes increased excretion of
      calcium and OHP and oophorectomy does not further aggravate the loss.

PMID- 8256656
TI  - Tumor necrosis factor alpha modulates parathyroid hormone action in UMR-106-01
      osteoblastic cells.
AB  - Tumor necrosis factor (TNF-alpha) has been shown to play an important role in
      local control of bone remodeling. The interaction of TNF-alpha and PTH was
      evaluated in UMR-106-01 cells, a phenotypic osteoblastic osteosarcoma cell line.
      We examined the influence of TNF-alpha on the two signal transduction systems
      triggered by PTH in UMR-106-01 cells, adenylate cyclase and free cytosolic
      calcium ([Ca2+]i). cAMP generation was inhibited in TNF-alpha-pretreated cells by
      69, 61, 34, and 21% at PTH concentrations of 0.1, 1, 10, and 100 nM,
      respectively. Inhibition was seen at TNF-alpha doses of 100-1500 units/ml after a
      minimum incubation time of 12 h. TNF-alpha inhibition of the PTH-stimulated
      increase in [Ca2+]i was even more pronounced: treated cells showed no change in
      baseline [Ca2+]i after stimulation with 40 nM PTH. Treatment with TNF-alpha was
      also found to inhibit both arms of the PTH response in the nontransformed
      osteoblastic cell line, MC3T3-E1. TNF-alpha treatment did not alter cAMP
      generation in response to PGE2. TNF-alpha inhibition of the PTH-stimulated cAMP
      response was reversed completely by addition of cholera toxin (5 micrograms/ml)
      and partially by forskolin (10 microM) but not pertussis toxin (100 and 500
      ng/ml). Scatchard analysis using PTHrP revealed that TNF-alpha treatment reduced
      the number of receptors but had no effect on KD. These findings suggest that TNF
      alpha inhibits the osteoblastic response to PTH at least in part because of a
      reduction in receptor number. Further investigation is indicated to provide
      insight into the interaction of calciotropic hormones and cytokines in vivo.

PMID- 8256657
TI  - Expression of annexin I, II, V, and VI by rat osteoblasts in primary culture:
      stimulation of annexin I expression by dexamethasone.
AB  - To determine whether rat osteoblasts synthesize proteins of the annexin family
      and to evaluate the extent to which glucocorticoids modulate the expression of
      annexins by these cells, osteoblasts were grown in primary cultures in the
      absence or presence of dexamethasone, and the expression of annexins was
      evaluated by immunoblotting using polyclonal antibodies against human annexins.
      Four different annexins (I, II, V, and VI) were found to be expressed by rat
      osteoblasts. The expression of annexin I, but not the other annexins studied, was
      increased in osteoblasts cultured in the presence of dexamethasone (173 +/- 33%
      increase comparing untreated cells and cells treated for 10 days with 5 x 10(-7)
      M dexamethasone). Increased expression of annexin I was observed after the third
      day of exposure to dexamethasone and rose thereafter until day 10; annexin I
      expression increased with dexamethasone concentrations above 10(-10) M throughout
      the range of concentrations studied. The increase in annexin I protein was
      associated with an increase in annexin I mRNA and was completely blocked by the
      concomitant addition of the glucocorticoid receptor antagonist RU 38486. The
      increase in annexin I content following dexamethasone treatment was associated
      with an increase in alkaline phosphatase activity and PTH-induced cAMP
      stimulation, whereas phospholipase A2 activity in the culture medium was reduced
      to undetectable levels. The finding that four annexins are expressed in rat
      osteoblasts in primary culture raises the possibility that these proteins could
      play an important role in bone formation by virtue of their ability to bind
      calcium and phospholipids, serve as Ca2+ channels, interact with cytoskeletal
      elements, and/or regulate phospholipase A2 activity. In addition, the
      dexamethasone-induced increase in annexin I may represent a mechanism by which
      glucocorticoids modify osteoblast function.

PMID- 8256658
TI  - Simple measurement of femoral geometry predicts hip fracture: the study of
      osteoporotic fractures.
AB  - Based on engineering principles, geometric measurements of femoral size should be
      related to femoral strength and the risk for hip fracture. To evaluate whether a
      simple measurement of femoral geometry is associated with hip fracture risk, we
      obtained dual x-ray absorptiometry scans of the proximal femur on 8074 white
      women age 67 or older. During an average of 1.6 years of follow-up, 64
      participants suffered hip fractures. In all fracture cases and in a random sample
      of 134 women who did not subsequently suffer a hip fracture, we measured hip axis
      length (the distance from greater trochanter to inner pelvic brim), neck width,
      and the neck/shaft angle on the scan printout, with the observer blinded to
      subsequent fracture status of the participant. Results were analyzed using
      multiple logistic models, and odds ratios were determined. After adjustment for
      age, each standard deviation decrease in femoral neck bone mineral density
      increased hip fracture risk 2.7-fold (95% confidence interval 1.7, 4.3), and each
      standard deviation increase in hip axis length nearly doubled the risk of hip
      fracture (odds ratio = 1.8; 95% CI 1.3, 2.5). The relationship between hip axis
      length and fracture risk persisted even after adjustment for age, femoral neck
      density, height, and weight. A longer hip axis length was associated with an
      increased risk of both femoral neck (OR = 1.9; 95% CI 1.3, 3.0) and trochanteric
      fractures (1.6; 1.0, 2.4). We found no significant association between the neck
      width (1.1; 0.8, 1.5) or the neck/shaft angle (1.4; 0.9, 2.2) and risk of hip
      fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256659
TI  - Stimulation by interleukin-1 of renal calcium reabsorption in
      thyroparathyroidectomized rats.
AB  - Recombinant human interleukin-1 (rhIL-1) can induce an elevation in calcium that
      has been ascribed exclusively to the stimulation of bone resorption. In the
      present study, we investigated whether rhIL-1 could also enhance the renal
      tubular reabsorption of calcium. The chronic influence of recombinant human rhIL
      1 on renal calcium transport was investigated in thyroparathyroidectomized rats.
      Administration of rhIL-1 at the dose of 1.5 micrograms/day sc for 6 days induced
      a significant elevation in plasma calcium that was associated with a slight but
      significant decrease in the urinary excretion of calcium. Recording of the
      urinary calcium excretion expressed per ml glomerular filtrate at various plasma
      calcium levels, as achieved by acutely infusing calcium gluconate, indicates that
      rhIL-1 enhanced the tubular reabsorption of calcium. The calculated index of the
      tubular reabsorption of calcium (TRCal) was significantly increased by rhIL-1
      (2.18 +/- 0.14 versus 1.79 +/- 0.07 mmol/l GFR, p < 0.05, in vehicle-treated
      rats). The change in the renal handling of calcium was not associated with
      stimulation of the tubular reabsorption of magnesium. Acute administration of a
      large dose (24 micrograms given in a bolus IV injection) of rhIL-1 enhanced
      within minutes the urinary excretion of prostaglandin E2. This effect was
      followed by a significant increase in urinary cAMP excretion and associated with
      a lower urinary calcium excretion. In conclusion, the results presented in this
      study indicate that rhIL-1 administered chronically selectively stimulated the
      tubular reabsorption of calcium. Experimental evidence suggests that this effect
      is mediated by prostaglandin-induced cAMP generation. These data strongly suggest
      that changes in the tubular handling of calcium could contribute to rhIL-1
      induced hypercalcemia.

PMID- 8256661
TI  - Circulating levels of vitamins K1 and K2 decreased in elderly women with hip
      fracture.
AB  - We measured the serum levels of phylloquinone (vitamin K1) and of the
      menaquinones, MK-7 and MK-8, in a group of 51 women with a mean age of 81 years
      who were studied within a few hours after a hip fracture. A group of 38 healthy
      age-matched women randomly chosen from the same population served as controls.
      Patients with hip fracture had a marked reduction in serum vitamin K1 (336 +/-
      302 versus 585 +/- 490 pg/ml, p < 0.01), MK-7 (120 +/- 84 versus 226 +/- 178
      pg/ml, p < 0.001), and MK-8 (89 +/- 113 versus 161 +/- 145 pg/ml, p < 0.01), and
      a large number had undetectable levels, especially of MK-8. Vitamin K levels were
      not correlated with the time elapsed after fracture or with serum cortisol or
      other biochemical variables. These data suggest that patients with hip fracture
      have vitamin K deficiency, an abnormality that could affect bone metabolism
      through an impairment of the gamma carboxylation of the gla-containing proteins
      of bone.

PMID- 8256660
TI  - Long-term fracture prediction by bone mineral assessed at different skeletal
      sites.
AB  - Bone mineral density (BMD) was measured at the lumbar spine and cervical and
      intertrochanteric regions of the proximal femur by dual-photon absorptiometry and
      bone mineral content was assessed at the distal and midradius by single-photon
      absorptiometry in an age-stratified random sample of 304 Rochester, Minnesota
      women aged 30-94 years. Over follow-up extending to 10 years (median 8.3 years),
      93 women experienced 163 new fractures. After adjusting for age, these bone
      mineral measurements predicted the likelihood of any incident fracture due to
      moderate trauma, with relative hazards varying from 1.4 to 1.6 per SD decrease in
      baseline bone mineral. A 1 SD decrease in lumbar spine BMD increased the risk of
      a new vertebral fracture comparably to a 17 year increase in age; a 1 SD decrease
      in femoral BMD was comparable to a 13-14 year increase in age on the risk of a
      hip fracture. We conclude that bone mineral measurements made at a variety of
      skeletal sites can predict the occurrence for at least 8-10 years of moderate
      trauma fractures of the sort that might be related to osteoporosis.

PMID- 8256662
TI  - Reactive oxygen species activate and tetracyclines inhibit rat osteoblast
      collagenase.
AB  - Recent studies have demonstrated that tetracyclines (TCs) scavenge reactive
      oxygen species (ROS). Hypochlorous acid (HOCl), an ROS produced by neutrophils,
      has been shown to activate neutrophil procollagenase. The objective of the
      present study was to determine whether (1) HOCl also activated osteoblast
      procollagenase and (2) TCs inhibited this enzyme in the presence of HOCl. HOCl (5
      microM) activated the proenzyme approximately sixfold (P < 0.01) from the medium
      of PTH-treated UMR-106-01 osteoblastic osteosarcoma cells as determined by
      functional collagenase assay (3H-methyl-labeled collagen substrate). Doxycycline
      (50-400 microM) and chemically modified tetracycline, CMT-1 (100-400 microM),
      significantly inhibited collagenase activity 50-90% and 40-80%, respectively, in
      the presence of 5 microM HOCl. Concentrations of 6-25 microM doxycycline and 10
      50 microM CMT-1 had no significant effect. Furthermore, an excess concentration
      of cation (50 mM CaCl2 or 50 microM ZnCl2) added to the incubation mixtures
      containing either doxycycline or CMT-1 did not restore collagenase activity, as
      demonstrated by SDS-PAGE-fluorography. These data suggested that TCs reduced
      available HOCl and thus prevented the hypochlorous acid conversion of the
      osteoblast proenzyme to active collagenase. TCs may have therapeutic potential in
      the treatment of periodontitis and other diseases by several mechanisms that
      inhibit pathologic collagen breakdown.

PMID- 8256664
TI  - Cloning and characterization of the 5'-flanking region of the mouse tartrate
      resistant acid phosphatase gene.
AB  - Little information is available on the molecular mechanisms controlling
      osteoclastic bone resorption. We used tartrate-resistant acid phosphatase (TRAP)
      to begin to investigate the regulation of bone resorption at the molecular level.
      TRAP is expressed at high levels in osteoclasts and may play an important role in
      the bone resorptive process. Therefore, we isolated the murine TRAP gene from a
      mouse spleen genomic library and characterized its promoter. A restriction map
      was generated for the 17 kb TRAP insert. A 2 kb SmaI fragment, containing the 5'
      flanking region, was subcloned and the nucleotide sequence determined. Sequence
      analysis of the SmaI fragment revealed the presence of numerous candidate
      transcription factor binding sequences, including those for AP1 and H-APF-1. The
      H-APF-1 site matches the consensus sequence for the IL-6-regulated transcription
      factor. An intron was identified at -1 to -393 bp relative to the ATG. The
      presence of an intron was confirmed by PCR analysis of RNA isolated from murine
      osteoclasts. Primer extension analysis indicated the presence of a transcription
      initiation site at -552 bp from the ATG. The region from -1846 to 2bp relative to
      the ATG initiation codon drove the transient expression of a luciferase reporter
      gene when transfected into HRE H9 rabbit endometrial cells. PMA treatment of HRE
      H9 cells enhanced luciferase transcription approximately threefold. These data
      suggest that the TRAP promoter is complex and contains multiple regulatory
      elements. The availability of the TRAP promoter may also permit production of
      transgenic mice, which can be used to develop previously unavailable osteoclast
      cell lines.

PMID- 8256663
TI  - Parenteral pamidronate prevents thyroid hormone-induced bone loss in rats.
AB  - Pamidronate (APD) is a bisphosphonate that prevents bone loss from a variety of
      causes. We studied the role of APD in preventing thyroid hormone-induced bone
      loss. A total of 32 rats were assigned to one of four treatment groups: (1) 
      APD/triiodothyronine (-T3), (2) -APD/+T3, (3) +APD/-T3, or (4) +APD/+T3. In the
      first of two studies, the rats received APD for the first week and T3 for the
      second week, and then their blood was analyzed for alkaline phosphatase and
      osteocalcin. Alkaline phosphatase and osteocalcin were significantly higher (p <
      0.05) in hyperthyroid rats (-APD/+T3, 3.9 +/- 0.25 mukat/liter and 23 +/- 1.6 nM,
      respectively) than in control animals (2.53 +/- 0.28 mukat/liter and 18.3 +/- 1.4
      nM, respectively). Hyperthyroid rats pretreated with APD (+APD/+T3) had levels of
      alkaline phosphatase and osteocalcin no different from controls. In a second
      study, rats were divided into the same four groups, except they received
      APD/placebo and T3/placebo concomitantly for 3 weeks. At the end of the study,
      bone mineral density (BMD) of the femur, spine, and whole body was measured by
      dual-energy x-ray absorptiometry, and the calcium content of the femora was
      measured directly. In hyperthyroid rats (-APD/+T3) BMD was significantly lower
      than in controls in the spine (0.201 +/- 0.004 versus 0.214 +/- 0.002 g/cm2, p <
      0.05) and femur (0.204 +/- 0.003 versus 0.218 +/- 0.002, p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256665
TI  - [Ultrastructural immunohistochemical localization of elastin in the human
      trabecular meshwork].
AB  - An electron microscopy study on the distribution of elastin in the trabecular
      meshwork of normal human eyes and in that of eyes with primary open angle
      glaucoma (POAG) was done using a protein-A gold immunohistochemical method with
      antiserum to either alpha-elastin or tropoelastin. Four types of elastic fibers
      were found to have elastin: (1) elastic-like fibers without the sheath, (2)
      fibers surrounded with a sheath of periodic structure, (3) fibers surrounded with
      fine granular-like material, and (4) connecting fibrils. No individual
      differences were observed in the labeling for these four types of elastic fibers.
      Antigenic sites against elastin of the elastic fibers were observed mainly in the
      low electron density amorphous elements. In the subendothelial layer of Schlemm's
      canal of the eyes with POAG, a marked increase of elastin was noted within the
      area containing fine fibrillar-like material. This phenomenon did not occur in
      age-matched normal eyes. The results suggest that elastin plays an important role
      in the development of POAG.

PMID- 8256666
TI  - [Porcine trabecular meshwork organ culture].
AB  - In order to investigate whether porcine eyes could be useful for trabecular
      meshwork (TM) organ culture, changes in ultrastructure and synthesis of
      glycosaminoglycans (GAGs) of organ-cultured porcine TM were studied. The presence
      of thrombospondin was also detected in porcine TM, using an immunohistochemical
      method. Explants were cultured for periods of 7 to 21 days and subsequently some
      of them were labeled with 3H-glucosamine and 35S-sulfate for 48 hours. There was
      very little change in the ultrastructure of the explants during our culture
      periods. The total incorporation of 3H-glucosamine and 35S-sulfate into
      trabecular GAGs for up to 21 days showed similar patterns. Immunoreactivity for
      thrombospondin was found in the trabecular sheets. This organ culture system
      suggests a model for studying the various drug and hormone induced alterations in
      this tissue.

PMID- 8256667
TI  - [Magnetic resonance imaging study on rat sugar cataract].
AB  - Proton nuclear magnetic resonance (1H-NMR) is one of the most important methods
      for noninvasively evaluating the state of water in the biological system. It
      could be useful for evaluation of the early changes of cataract. In this study,
      in vivo magnetic resonance imaging (MRI) was applied to rat galactosemic
      cataract, which is a model of the human diabetic cataract, and compared with the
      histological findings. The relationship between the relaxation times (T1, T2) and
      the water contents were discussed. The T1 and T2 values were prolonged and the
      high intensity area of the lens cortex was enlarged from the early stage of the
      cataract (two days after the intake of galactose). These changes preceded the
      histological changes. This suggests that MRI is applicable for the evaluation of
      anti-cataract agents, for example aldose reductase inhibitors, against human
      diabetic cataract.

PMID- 8256668
TI  - [Fibronectin in the chorioretinal wound after laser photocoagulation].
AB  - Fibronectin (Fn) is a glycoprotein which mediates adhesion, extension, migration,
      and chemotaxis of the cells. We did a histochemical study of the time course of
      appearance and distribution of Fn in the chorioretinal wound after laser
      photocoagulation. In the normal chorioretinal tissue, Fn was detected in the
      internal limiting membrane, Bruch's membrane, and the endothelium of
      chorioretinal vessels. Shortly after laser photocoagulation, Fn appeared on
      Bruch's membrane and in the endothelium of choroidal vessels and choroidal
      stroma, and was prominent by one week after laser photocoagulation. Although Fn
      disappeared when wound healing was accomplished, it was still detected on Bruch's
      membrane one month after laser photocoagulation. These findings suggest that Fn
      is related to chorioretinal wound healing after laser photocoagulation.

PMID- 8256669
TI  - [Histological evaluation of brush cytology of rabbit conjunctiva].
AB  - The number of the cells and the layers of the conjunctiva which can be obtained
      by brush cytology was studied on rabbit conjunctiva using cytological and
      histological methods. About 1,000, 3,500, and 10,000 conjunctival epithelial
      cells can be obtained by 7, 14, and 20 brush strokes histological observations
      showed that all varieties of the layers including basal cells were obtained
      without destroying the basement membrane. This study showed that the brush
      cytology can offer single cell suspension only from the conjunctival epithelium,
      and that brush cytology is useful to investigate the conjunctival epithelium by
      flow cytometry, polymerase chain reaction, and other methods.

PMID- 8256670
TI  - [New membrane filter (PORETEC) method for ocular diagnostic cytopathology].
AB  - We describe a new membrane filter (PORETEC) technique for processing
      cytopathologic fluid specimens. This procedure provides excellent cytologic
      preparations because there is no background staining and only a small amount of
      fluid specimen is necessary, as there is little cell loss. We compared the number
      of cells collected by the membrane filter technique with that collected by
      cytocentrifugation using conjunctival brush cytology specimens from 6 subjects.
      The number of cells obtained by the new method was significantly higher than that
      obtained by the cytocentrifugation technique. This method was very useful for
      ocular fluid specimens such as aqueous humor, vitreous specimens, and scrapings
      from the cornea and conjunctiva. We showed some examples of these specimens
      including immunocytochemical staining done by this method. We confirm that this
      is valuable for diagnostic cytopathologic study of various fluid specimens in
      ophthalmology.

PMID- 8256671
TI  - [Anterior chamber dimensions in normal subjects on Kume Island, Okinawa].
AB  - The anterior chamber dimension and axial length were studied by photogrammetry
      and ultrasonography in 365 normal subjects over 21 years of age on Kume island,
      Okinawa. There was no difference between right and left eyes in the anterior
      chamber dimensions, corneal curvature, or axial length. Male subjects had a
      larger anterior chamber and longer axial length than female subjects. The volume,
      depth, and diameter of the anterior chamber diminished with age and degree of
      hyperopia. The axial length was related to the anterior chamber dimensions,
      corneal curvature, and degree of ametropia. The anterior chamber dimensions and
      axial length in subjects over 60 years of age on Kume island were significantly
      smaller than in normal subjects over 60 years in Tokyo.

PMID- 8256672
TI  - [Changes in corneal astigmatism with aging].
AB  - Change in physiologic corneal astigmatism due to aging was studied. A series of
      868 cases (1,660 eyes) was evaluated. These eyes were divided into 6 groups by
      age; A) below 40 years, B) in the 40's, C) in the 50's, D) in the 60's, E) in the
      70's, and F) over 80. Corneal astigmatism was examined with an autokeratometer.
      In Group A, 88.5% had with-the-rule astigmatism (WTR), whereas only 3.7% had
      against-the-rule astigmatism (ATR). The cylindrical diopter (CD) of WTR was 1.29
      +/- 0.73 D, which was significantly the largest among the groups. In Group C, WTR
      decreased to 55.9% and ATR increased to 22.9%. The CD of WTR also decreased to
      0.85 +/- 0.47 D. In Group E, WTR was 31.4% and ATR was 49.3%. The CD of ATR
      increased to 0.88 +/- 0.70 D. In Group F, WTR was 19.9%, whereas ATR was 65.9%.
      The CD of ATR was 1.48 +/- 0.88 D, which was the largest among the groups. As
      such, WTR was dominant at younger ages, and ATR increased with aging at older
      ages. The CD of WTR decreased, and ATR increased, with aging.

PMID- 8256673
TI  - [Long-term results of transscleral retinal detachment surgery with special
      reference to visual function].
AB  - We studied visual acuity and visual field of 44 eyes in 42 patients who had
      undergone transscleral retinal detachment surgery, they were classified into a
      preoperative group, a postoperative group, and a group ten years after surgery.
      With regard to visual acuity, the postoperative group showed a significant
      increase compared with the preoperative group (p < 0.001), and there was no
      significance between the postoperative group and the group ten years after
      surgery. In order to quantify the visual field obtained by Goldmann perimeter,
      the areal size of V-4 isopter, the areal size of I-4 isopter and the volume of
      the visual field were adopted in the present study. Each of the three mean values
      was high in the following order: the group ten years after surgery, the
      postoperative group, and the preoperative group. The mean value of the group ten
      years after surgery was respectively equivalent to 80.6%, 65.5%, and 71.1% of
      that of normal control in the order: the areal size of V-4 isopter, the areal
      size of I-4 isopter, and the volume of the visual field. Our results support the
      conclusion that the visual acuity acquired postoperatively can be maintained for
      ten years after surgery. The visual field acquired postoperatively also seems to
      be retained ten years after surgery.

PMID- 8256674
TI  - [Diagnostic vitrectomy for chronic uveitis].
AB  - Uveitis is diagnosed by ophthalmologic and systemic examination, but it may be
      difficult to diagnose accurately in some chronic cases. We performed diagnostic
      and therapeutic vitrectomy for chronic uveitis in 6 eyes of 4 patients, and
      examined vitreous specimens with immunohistochemical staining. Visual acuity
      improved in all cases due to clearing up of the vitreous cells. One patient had
      sarcoidosis, one had B cell malignant lymphoma (ocular reticulum cell sarcoma),
      and two had reactive lymphoid hyperplasia. Vitrectomy for chronic uveitis is
      useful for diagnosis and improvement of vision, and we recommend
      immunohistological staining of vitreous specimens. Particularly, when intraocular
      lymphoma is suspected, vitrectomy must be performed early.

PMID- 8256675
TI  - [Changes in optic disc rim color with glaucomatous visual field damage--a
      quantitative study on pattern of color changes].
AB  - We developed a new computerized method for measuring the color of the optic disc
      directly with objective reproductivity. We compared the optic disc color with
      sensitivity loss in visual fields corresponding to the disc area measured by
      Humphrey Field Analyzer. 11 normal eyes, 40 glaucomatous eyes, and 27 eyes with
      ocular hypertension were studied. In the temporal segment of the disc rim, with
      the exception of the area, a significant correlation between rim color and
      sensitivity loss was detected. In the nasal rim and macular area, however, the
      correlation was less significant in early stage glaucoma. Compared with normal
      discs, glaucomatous discs showed significant decrease in the red color element of
      the rim area, and some discs with ocular hypertension showed a decrease without
      any visual field defect.

PMID- 8256676
TI  - [Fluorescein angiographic findings regarding the optic disc in cases of low
      tension glaucoma and the chronic stage of anterior ischemic optic neuropathy].
AB  - The optic disc was studied by stereofluorescein angiography in 7 cases of the
      chronic stage of anterior ischemic optic neuropathy (AION) and 20 cases of low
      tension glaucoma (LTG), to clarify the difference in vasculature. In the LTG
      patients, a selective and well-defined decrease of laminar and prelaminar
      capillaries in the upper and (or) lower temporal area of the optic disc was found
      in 38 (95%) of 40 eyes in the 20 cases. In the AION patients, a decrease of
      laminar and prelaminar capillaries was also found in 3 (43%) of 7 eyes in the 7
      unilateral cases, but the specific area and form of vascular reduction were not
      found. These results show that the angiographic picture of the optic disc in LTG
      is clearly different from that in AION.

PMID- 8256677
TI  - [The clinical evaluation of UF-021, a new prostaglandin related compound, in low
      tension glaucoma patients].
AB  - We administered UF-021 isopropyl unoprostone (Rescula) ophthalmic solution, a new
      prostaglandin-related compound developed as an anti-glaucoma agent, to 13 low
      tension glaucoma patients for 24 weeks, and clinically evaluated the effect of
      the intraocular pressure (IOP) reduction, visual field change, and side effects
      of the agent. Intraocular pressure was reduced in 11 out of 12 patients who were
      studied for statistical analysis. In these 12 patients, significant IOP reduction
      was recognized in the mean IOP for 24 weeks after the administration of UF-021.
      No side effects were detected in any of the 13 patients. From these results, UF
      021 could be used as a new anti-glaucoma agent for low tension glaucoma, and also
      safer than many other anti-glaucoma agents.

PMID- 8256678
TI  - [Convergence-retraction nystagmus associated with vascular disorders of the
      brainstem].
AB  - We report two cases of convergence-retraction nystagmus due to cerebral
      infarction and hemorrhage. Magnetic resonance imaging disclosed a small area of
      abnormal signal in the thalamo-mesencephalic junction in each patient. This
      lesion appeared to include the rostral interstitial nucleus of the medial
      longitudinal fasciculus (rostral iMLF). The precise oculography of nystagmus in
      these patients demonstrated the fast adductive movements and slow exponential
      tract of abduction. The velocity of the fast phase was equal to or less than that
      of ordinary saccadic eye movements. The time constant of the slow phase was about
      0.3 second. These characteristics are identical to those of pineal tumor cases.

PMID- 8256679
TI  - [Cataracts in a patient treated with busulfan (Mablin powder) for eight years].
AB  - Busulfan (Mablin powder) has been used in the treatment of chronic myelogenous
      leukemia for a long time. Although cataract is known to be an ocular side effect
      of prolonged Busulfan therapy, it has rarely been reported, especially in Japan.
      This report describes mature cataracts in a 59-year-old woman with chronic
      myelogenous leukemia, who had received a total dose of 2,249.7 mg Busulfan over
      eight years. In our department, the average age at the time of senile cataract
      operation was 72 years in men and 73.4 years in women during the past five years,
      so this patient was younger than the average senile cataract patient. A review of
      case reports, including the present one, suggests that Busulfan cataract
      characteristically develops rapidly in both eyes of young patients treated with a
      total dose of over 2,000 mg of Busulfan for more than four years. Busulfan
      cataracts have rarely been reported probably because cataract is regarded as
      senile and patients treated with Busulfan usually die before cataract appears.

PMID- 8256680
TI  - [Neuroendocrine tumors of the prostate].
AB  - Neuroendocrine carcinomas of the prostate is rare and usually concern patients
      with an initial diagnosis of adenocarcinoma of the prostate which become
      refractory to hormonal treatment. Here is reported the case of a patient who
      presented with a primary neuroendocrine tumor of the prostate. A review of the
      literature shows the differences with usual adenocarcinoma and the diagnostic and
      therapeutic implications.

PMID- 8256681
TI  - Hypervascularization of the glans penis after a venous leakage and
      revascularisation procedure: a case report.
AB  - A patient, in which unsuccessful venous leakage procedure followed by
      revascularisation of the penis, lead to a hypervascularization of the glans and
      important oedema of the penis is presented. After embolization of the epigastric
      artery, these symptoms disappeared and the patient had normal erectile function.

PMID- 8256682
TI  - Incrusted cystitis after intravesical mitomycin C treatment.
AB  - Bladder wall calcification is a rare complication of intravesical therapy of
      superficial bladder cancer with Mitomycin C. A review of the literature revealed
      2 other cases. We report a new case and discuss the pathogenic mechanism of this
      consequence of the intravesical treatment with Mitomycin C.

PMID- 8256683
TI  - [Hemangiopericytoma: a case report].
AB  - We describe one case of hemangiopericytoma touching a 44-year-old man. It is a
      rare vascular tumor originating from pericytes surrounding capillaries. The main
      typical features of it are the difficulty in doing an histologic diagnosis and
      the impossibility to make out a reliable prognosis. The therapy of choice is a
      surgical procedure sometimes in combination with radio- and/or chemotherapy.

PMID- 8256684
TI  - Vaginal leiomyoma: the female prostate.
AB  - We report one case of vaginal leiomyoma revealed by dysuria operated with
      success. Our observation are discussed with the review of the literature data.

PMID- 8256685
TI  - Urinary retention due to prostatic involvement in testicular lymphoma: a case
      report.
AB  - Testicular involvement was the first manifestation of malignant lymphoma in the
      present case; after six months the disease became generalized but repeated
      chemotherapy achieved amelioration with negative bone-marrow biopsy after one
      year. Then urinary retention appeared, due to prostatic involvement from primary
      testicular lymphocytic lymphoma. We believe that this is the first reported case
      of primary malignant lymphoma of the testicle with secondary localization to the
      prostate and acute urinary retention.

PMID- 8256686
TI  - [Non-Hodgkin's lymphoma: unusual testicular localization: case report].
AB  - We report on a 58-year-old man, in whom a clinical suspicion of orchitis of the
      right testicle was treated with antibiotics. The instored antibiotics failed to
      improve the clinical condition of orchitis. Previous medical history revealed a
      gastric lymphoma for which gastrectomy was performed, followed by combination
      chemotherapy. Therefore testicular biopsies were performed. These biopsies
      confirmed the diagnosis of testicular localisation of lymphoma. A combination
      chemotherapy, in association with alpha-Interferon was instaured. One year after
      instauration of combination therapy, the patient is in complete remission. This
      unusual localisation of lymphoma is discussed in regard of other cases described
      in literature.

PMID- 8256687
TI  - The value of performing both IVU and DMSA scan in patients with urinary stone
      disease.
AB  - A study of 60 patients with stone disease was done, all patients had an IVU and
      DMSA scan. A DMSA scan helps to show clear cortical images, diagnose cortical
      scars and absence of cortical tissue. While the IVU allows gross evaluation of
      kidney function and morphological changes, the DMSA scan is an accurate measure
      of functioning renal mass. Anyhow, both studies are complementary to each other
      in patients with stones disease.

PMID- 8256688
TI  - Inhibition and enhancement in the analysis of airborne endotoxin levels in
      various occupational environments.
AB  - Inhibition and enhancement effects on the Limulus Amebocyte Lysate (LAL) assay
      were studied in a series of endotoxin exposure samples from various occupational
      environments. Two types of analyses were performed, with various dilutions and
      with spiked samples. Results showed that inhibition and enhancement occurred in
      some samples, leading to respective underestimation and overestimation of the
      endotoxin concentration. When inhibition or enhancement is present, the result of
      this study shows that large differences in endotoxin concentration may be found,
      depending on the dilution at which the sample is analyzed. False conclusions
      about exposure levels and their potential health effects might be introduced.
      Results show that quality control procedures need to become standard practice
      when endotoxins are analyzed in occupational environments and development of a
      validated, generally accepted protocol should be encouraged.

PMID- 8256689
TI  - Variation of exposure between workers in homogeneous exposure groups.
AB  - It is generally assumed that workers employed in the same job at a given location
      are uniformly exposed, i.e., that they have the same long-term mean exposure.
      This assumption has led to observational schemes for classifying workers into
      homogeneous exposure groups (HEGs), based on job title, location, and other
      identifiable features of the work environment. This paper presents results from
      analysis of 183 HEGs (comprised of 15,495 personal measurements) in which it was
      possible to determine the between-worker component of variance in exposure. The
      results indicate that, contrary to popular belief, only about one fifth of the
      HEGs were uniformly exposed (less than a two-fold difference among 95% of
      individual mean exposures) while an equal number showed a high degree of
      variation between workers (more than 15-fold differences among 95% of
      individuals). Further analyses indicate that the identifiable features of the
      work environment, which are typically used to establish HEGs, are only marginally
      related to the between-person variation (accounting for only 13% of this variance
      component). It is concluded that industrial hygienists should not rely on
      observational schemes to guarantee that groups of workers are uniformly exposed.
      Rather, they should adopt methods of statistical sampling and analysis that allow
      the variance components to be estimated so that decisions regarding the
      evaluation of hazard and selection of controls will be appropriate.

PMID- 8256690
TI  - A survey of airborne HDI, HDI-based polyisocyanate and solvent concentrations in
      the manufacture and application of polyurethane coatings.
AB  - This study summarizes the results of industrial hygiene surveys performed between
      1979 and 1987 in paint manufacturing and application operations using
      polyurethane coatings containing hexamethylene diisocyanate (HDI) and HDI-based
      polyisocyanates (trade name Desmodur N). A total of 466 Desmodur N and 457 HDI
      samples were collected from 47 operations most of which were in application. The
      application surveys covered manufacture and refinishing of transportation
      vehicles, painting of large military and civilian equipment, industrial finishing
      operations, and maintenance and construction operations. The primary objective of
      the surveys was to assess the potential exposure to HDI and HDI-based
      polyisocyanate. In more than 60% of the surveys, concentrations of airborne
      organic solvents also were monitored. Isocyanates were sampled using
      toluene/nitroreagent in midget impingers, and solvents were collected using
      charcoal tubes. They were analyzed using high pressure liquid chromatography and
      gas chromatography, respectively. The data from these workplace situations show
      there is some potential for isocyanate overexposure of unprotected workers and
      that it is greater in spray than in nonspray operations.

PMID- 8256691
TI  - A hazard and operability study of anhydrous ammonia application in agriculture.
AB  - Researchers from the National Institute for Occupational Safety and Health
      (NIOSH) applied Hazard and Operability (HAZOP) analysis to examine hazards during
      the use of anhydrous ammonia by farmers. This analysis evaluated the storage,
      transfer, and application of anhydrous ammonia, identifying credible hazard
      scenarios, practical solutions, and research needs. Ninety-five findings were
      developed that are of use to farmers, distributors of ammonia and application
      equipment, and manufacturers of application equipment. The findings generally
      involve training, equipment design changes, preventive maintenance, and material
      compatibilities. The HAZOP team found that additional safety features need to be
      developed or implemented. The study also pointed out where correct operator
      procedure and preventive maintenance can prevent inadvertent releases. Other
      inadvertent releases are caused by incompatible materials, or by using equipment
      in ways other than intended. Several examples of the findings are given to
      emphasize the HAZOP technique and the high-risk scenarios. Strategies for
      dissemination to the agricultural community are presented.

PMID- 8256692
TI  - Health and safety's stewardship of key business values: employees, public trust,
      and responsibility to shareholders.
AB  - This paper reviews how one company has been able to develop and implement a
      highly effective job safety and health system and to sustain it at a high level
      of performance. This process begins with a simple but clear corporate safety and
      health policy statement: "Procter & Gamble insists on safe operation." It is
      driven by three critical values, namely: 1) its employees, 2) its public trust,
      and 3) its profits. The impact of workers' compensation costs on company profits
      is examined, along with the enormous savings in these costs that have been
      achieved by the company's commitment to total quality. This is followed by brief
      descriptions of the company's "Total Incident Rate" and it's "Key Elements"
      systems, and the relationships between them. The paper concludes with a
      description of the company's model for enabling all employees to make
      recommendations for continuous improvement of health and safety systems
      throughout all of the company's operations.

PMID- 8256693
TI  - Do workers' compensation laws protect industrial hygienists from lawsuits by
      injured workers?
AB  - Workers' compensation laws provide injured employees with a swifter, more
      certain, and less litigious system of compensation than existed under the common
      law. Although workers' compensation is almost always an injured employee's
      exclusive remedy against the employer, the employee may bring a common-law tort
      action against a "third party" who may be liable in whole or in part for the
      employee's injury. This article investigates whether industrial hygienists are
      "third parties" and therefore subject to suit by injured employees who claim that
      industrial hygienists negligently caused their injuries. The author concludes
      that in most states, where the industrial hygienist and the injured worker are
      fellow employees, the industrial hygienist shares the employer's immunity from
      suit. As to the consultant who performs industrial hygiene services as an
      independent contractor, the author concludes that the employer's nondelegable
      duty to provide a safe workplace offers industrial hygiene consultants an
      argument that they share the employer's immunity from suit. Countervailing
      arguments, however, leave the industrial hygiene consultant vulnerable to
      negligence claims in many jurisdictions. There is a trend among the states to
      extend the employer's immunity to those who provide safety and health services to
      the employer.

PMID- 8256694
TI  - Relation of coronary artery disease in women < 60 years of age to the combined
      elevation of serum lipoprotein (a) and total cholesterol to high-density
      cholesterol ratio.
AB  - After age 40 years, coronary artery disease (CAD) is the leading cause of death
      in both women and men, yet in women the factors associated with, or leading to,
      CAD have been less extensively studied. This study examined the strength of
      association of a number of risk factors to CAD in groups of women < 60 years of
      age with (n = 108) and without (n = 66) angiographically documented significant
      narrowing of coronary arteries. In univariate analyses, there were significant
      differences between control subjects and patients with regard to age (49 +/- 6 vs
      52 +/- 7 years) and total lipids and apolipoproteins measured. The relative
      frequency of cigarette smoking and diabetes was higher and that of estrogen
      replacement therapy lower in patients with CAD than in control subjects. In
      multivariate analysis the following factors were independently associated with
      CAD (adjusted odds ratios and 95% confidence intervals): total cholesterol to
      high-density lipoprotein (HDL) cholesterol (1.91; 1.56 to 2.34); lipoprotein (a)
      (10.66; 3.51 to 32.35); estrogen replacement (0.24; 0.11 to 0.54); age (1.12;
      1.04 to 1.18); and smoking (1.50; 0.98 to 2.29). The nonadjusted odds ratio of
      CAD, based on combined tercile values of lipoprotein (a) serum level and total
      cholesterol to HDL cholesterol ratio, was very low (0.15; 0.06 to 0.36) when both
      values were within the first tercile, but very high (16.63; 3.54 to 78.07) when
      both were in the third tercile.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256695
TI  - Usefulness of dobutamine echocardiography for detecting restenosis after
      percutaneous transluminal coronary angioplasty.
AB  - To determine the usefulness of dobutamine stress echocardiography for detecting
      restenosis after percutaneous transluminal coronary angioplasty, the results of
      coronary arteriography and dobutamine stress echocardiography were compared in
      103 patients 6 months after percutaneous transluminal coronary angiography. The
      dobutamine stress echocardiograms were obtained on the same day as the coronary
      arteriograms, which were analyzed by both quantitative and visual estimates of
      luminal narrowing. The angiographic restenosis rate was 44% by quantitative and
      31% by visual estimates of stenosis. Dobutamine stress echocardiography was
      abnormal in 38% of previously dilated regions with restenosis and normal in 79%
      of previously dilated regions without restenosis by quantitative coronary
      angiography. Dobutamine stress echocardiography was concordant in 69% of 16
      patients with multivessel disease compared with 40% of 41 patients with 1-vessel
      disease (p < 0.05). By quantitative coronary angiography, 64% of patients with
      significant disease in the left anterior descending artery were identified by
      dobutamine stress echocardiography compared to 12 and 24% of patients with
      disease in the left circumflex and right coronary arteries, respectively (p <
      0.009). Concordance was seen in 79% of patients with baseline wall motion
      abnormalities compared with 54% of patients without baseline wall motion
      abnormalities. Dobutamine stress echocardiography has a low sensitivity but high
      specificity for detecting restenosis after coronary angioplasty, which may be
      explained in part by the high prevalence of 1-vessel disease in this patient
      population. The variables associated with significantly higher degrees of
      concordance were the presence of left anterior descending artery disease,
      multivessel disease, and baseline wall motion abnormalities.

PMID- 8256697
TI  - Measurement by intracoronary ultrasound of in vivo arterial distensibility within
      atherosclerotic lesions.
AB  - Arterial distensibility is diminished by atherosclerosis. This process has not
      been well studied in the coronary arteries. The purpose of this study was to
      assess changes in coronary arterial distensibility in 4 groups of patients. Group
      I (n = 20) consisted of patients with normal vessels, group II (n = 40) with
      diseased undilated vessels, group III (n = 15) after successful percutaneous
      transluminal coronary angioplasty (PTCA), and Group IV (n = 20) after successful
      directional coronary atherectomy (DCA). Intracoronary ultrasound imaging was used
      to assess distensibility, plaque morphology and atherosclerotic burden (expressed
      as the percentage of total vessel cross-sectional area occupied by plaque:
      percent plaque area). Distensibility was defined as percent change in lumen area
      in a cardiac cycle. Group I (normal vessels) had a distensibility = 14 +/- 5%,
      which was significantly greater than that seen in group II (distensibility = 4 +/
      2%, p < 0.001). In undilated vessels, distensibility was related to the degree
      of atherosclerotic burden (r = 0.75). This relation was curvilinear with a marked
      decrease in distensibility when percent plaque area exceeded 30%. Distensibility
      in group III (after PTCA) was higher than in group II (10 +/- 3 vs 4 +/- 2%, p <
      0.001) despite a larger plaque burden (percent plaque area of 56 +/- 12 vs 46 +/-
      11%, p < 0.005). The distensibility in group IV (after DCA) was also higher than
      in group II (8 +/- 4 vs 4 +/- 2%, p < 0.001) despite a similar residual percent
      plaque area (49 +/- 13 vs 46 +/- 11%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256696
TI  - Comparison of dobutamine and exercise echocardiography for detecting coronary
      artery disease.
AB  - There has been no study comparing the efficacy of dobutamine and exercise
      echocardiography in detecting coronary artery disease (CAD) or their physiologic
      effects at ischemic threshold in the same group of patients. To accomplish this,
      52 patients presenting for coronary angiography underwent supine ergometer
      exercise and dobutamine echocardiography. Compared with angiography, the overall
      sensitivity of detecting CAD was 78% for exercise and 86% for dobutamine
      echocardiography (p = NS). The sensitivities of detecting patients with 1-, 2-, 3
      and multivessel CAD with exercise echocardiography were 63, 80, 100 and 90%,
      respectively, and with dobutamine echocardiography 75, 90, 100 and 95%,
      respectively (p = NS, exercise vs dobutamine). The specificity of both tests was
      87%. At ischemic threshold, heart rate was significantly lower with dobutamine
      than with exercise echocardiography (91 +/- 3 vs 114 +/- 3 beats/min; p < 0.001),
      systolic blood pressure was significantly lower with dobutamine testing (155 +/-
      5 vs 176 +/- 6 mm Hg; p < 0.01), and rate-pressure product was significantly
      lower with dobutamine stress (14.1 +/- 0.7 vs 19.8 +/- 0.8 x 10(3) beats/min x mm
      Hg; p < 0.001). It is concluded that the efficacy of detecting CAD by exercise
      and dobutamine echocardiography is comparable, and the physiology at ischemic
      threshold of the 2 methods is significantly different and suggests a different
      means of inducing myocardial ischemia.

PMID- 8256698
TI  - Noninvasive assessment of coronary flow dynamics before and after coronary
      angioplasty using transesophageal Doppler.
AB  - Recent invasive studies using intracoronary Doppler catheters or guide wires
      reported improved coronary flow dynamics after successful percutaneous
      transluminal coronary angioplasty. Transesophageal Doppler enables the
      measurement of coronary flow velocities within the left anterior descending
      artery. The present study was designed to test: (1) whether transesophageal
      Doppler may detect coronary flow velocity changes in patients undergoing
      angioplasty for left anterior descending artery stenosis, and (2) whether this
      technique may help to evaluate non-invasively the results of the procedure.
      Twenty-three patients undergoing angioplasty of the left anterior descending
      artery were studied by transesophageal Doppler before and < or = 24 hours after
      the interventional procedure. Coronary flow velocities were measured in the
      proximal part of the left anterior descending artery with the use of pulsed
      Doppler guided by color flow imaging. The degree of stenosis was measured by
      computerized quantitative coronary arteriography. Coronary flow velocity signals
      were successfully obtained in 19 of 23 patients (83%). In 16 successful
      angioplasty procedures, peak diastolic velocity increased from 37 +/- 14 cm/s
      before angioplasty to 51 +/- 16 cm/s after (p = 0.0001). In the 3 patients in
      whom angioplasty was unsuccessful, transesophageal Doppler showed no significant
      increase in peak diastolic coronary flow velocity. In a total of 19 angioplasty
      procedures, a good linear relation was found between the percent changes in
      coronary flow diastolic velocity and the reduction in the degree of stenosis (r =
      0.85; p = 0.0001). All patients with > 20% increase in peak diastolic velocity
      had > 40% stenosis reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256699
TI  - Efficacy and safety of extended-release isosorbide mononitrate for stable effort
      angina pectoris.
AB  - The efficacy and safety of extended-release isosorbide mononitrate tablets were
      evaluated in patients with stable effort angina. In a double-blind study, 313
      patients with stable effort-induced angina were randomized to receive placebo or
      extended-release isosorbide mononitrate: 30, 60, 120 or 240 mg once daily in the
      morning. Serial exercise testing was performed using the standard Bruce treadmill
      protocol on days 1, 7, 14, 28 and 42 immediately before morning drug
      administration, and 4 and 12 hours after administration. After initial dosing,
      all groups that received extended-release isosorbide mononitrate had significant
      (p < 0.01) increases in mean total exercise time of approximately 30 to 50
      seconds in relation to placebo 4 and 12 hours after administration. On day 42,
      mean changes from baseline in total exercise time of patients who received 120 or
      240 mg of extended-release isosorbide mononitrate exceeded placebo by
      approximately 50 to 60 seconds 4 hours after dosing (p < 0.01), and by 30 to 35
      seconds 12 hours after dosing (p < or = 0.05). No significant difference was
      detected between responses to extended-release isosorbide mononitrate and placebo
      24 hours after administration (i.e., immediately before the next dose). Thus,
      there was neither significant activity nor demonstrable rebound of effort-induced
      angina (zero-hour effect) at the end of the dosing interval. Transient headache
      was the most prevalent adverse experience. Extended-release isosorbide
      mononitrate (120 and 240 mg administered orally once daily) significantly
      prolonged exercise time to development of moderate effort-induced angina 4 and 12
      hours after dosing during long-term therapy, without development of nitrate
      tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256700
TI  - Dipyridamole thallium-201 imaging versus dobutamine echocardiography for the
      evaluation of coronary artery disease in patients unable to exercise.
AB  - The present study used 51 patients in a prospective, crossover, blinded
      comparison of dipyridamole thallium-201 imaging and dobutamine echocardiography
      for (1) detection of coronary artery disease (CAD), (2) detection of inducible
      ischemia, and (3) determination of myocardial viability. The detection of CAD was
      based on quantitative defects on initial planar thallium-201 images and resting
      or inducible wall motion abnormalities on echocardiography. Detection of ischemia
      was based on redistribution on delayed thallium-201 images and inducible wall
      motion abnormality on echocardiography. The myocardium in a region with resting
      wall motion abnormality was considered viable if it showed either redistribution
      or > 50% activity on delayed thallium-201 images, and if regional function either
      improved or worsened on echocardiography. The tests were comparable for the
      detection of CAD (53 and 59%, respectively, p = 0.23). Thallium-201 was superior
      to echocardiography for the detection of ischemia (35 vs 14%, respectively, p =
      0.01). Although the incidence of viable myocardium was equivalent by the 2 tests
      (100 and 96%, respectively, p = 0.99) for each abnormally moving segment in the
      24 patients with resting wall motion abnormality on echocardiography, it was
      greater on thallium-201 imaging (98 vs 68%, p < 0.01). It is concluded that
      because of its better ability to detect inducible myocardial ischemia and
      determine viability in myocardial segments showing reduced function, dipyridamole
      thallium-201 imaging appears to be superior to dobutamine echocardiography for
      the evaluation of CAD in patients unable to exercise.

PMID- 8256701
TI  - Influence of left ventricular function on survival and mode of death after
      implantable defibrillator therapy (Cleveland Clinic Foundation and Montefiore
      Medical Center experience).
AB  - To determine the influence of left ventricular (LV) function on survival and mode
      of death in patients with an implantable cardioverter-defibrillator (ICD), sudden
      death, surgical mortality, total arrhythmia-related death, total cardiac death
      and total death were retrospectively evaluated in 377 consecutive patients. The
      outcomes were also compared between patients with an LV ejection fraction > or =
      30% (214 patients, group 1) and < 30% (148 patients, group 2). Surgical mortality
      was 3.9% (1.8% in group 1, 7% in group 2). During the follow-up of 25 +/- 20
      months, actuarial survival rates of all patients at 3 years were 96% for sudden
      deaths, 81% for total cardiac deaths and 74% for total mortality. When the 2
      groups were compared, survival rates of groups 1 and 2 at 3 years, respectively,
      were 99 and 90% for sudden death (p < 0.05), 97 and 84% for sudden death and
      surgical mortality (p < 0.01), 94 and 80% for the total arrhythmia-related death
      (p < 0.001), 88 and 68% for total cardiac death (p < 0.0001), and 81 and 62% for
      total mortality (p < 0.002). In group 2, 73% of total cardiac deaths within 1
      year were causally related to the arrhythmia. Thus, in patients with an ICD,
      sudden death rates were very low. However, total cardiac death and total death
      rates were relatively higher. The outcomes of patients with an ICD were strongly
      influenced by the degree of LV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256702
TI  - Ventricular septal summit stimulation in atrioventricular nodal reentrant
      tachycardia.
AB  - In all, 18 consecutive patients with atrioventricular nodal reentry tachycardia
      (AVNRT) underwent right ventricular (RV) stimulation during AVNRT from either the
      RV apex or summit. Stimulation from the RV apex advanced the tachycardia with the
      same atrial sequence in 6 of 18 patients (33%), but never conclusively excluded
      the presence of a low atrial tachycardia. RV summit stimulation resulted in
      direct stimulation of the low septal right atrium in 6 patients. RV summit
      stimulation advanced the tachycardia in 4 patients, delayed it in 2 and
      terminated it in 3 without an atrial electrogram. The latter 2 findings exclude
      the presence of a low atrial tachycardia. Thus, in patients with AVNRT,
      application of extrastimuli closer to the putative reentrant site enables greater
      efficacy in tachycardia resetting and in excluding a low septal atrial
      tachycardia.

PMID- 8256703
TI  - The 12-lead electrocardiogram in midseptal, anteroseptal, posteroseptal and right
      free wall accessory pathways.
AB  - The 12-lead electrocardiograms of 50 patients with 1 anterogradely conducting
      accessory pathway were analyzed to obtain characteristics of electrocardiographic
      findings in the midseptal, anteroseptal, true posteroseptal and right free wall
      accessory pathway locations. Locations were confirmed by surgery (33 patients) or
      radiofrequency catheter ablation (17 patients). This study analyzed (1) QRS in
      the frontal plane, (2) delta wave axis in the frontal plane, (3) the angle
      between QRS and delta wave axes, (4) the R/S ratio in lead III, (5) negativity of
      delta wave in inferior leads, and (6) the R/S ratio in precordial leads.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256704
TI  - Determinants of induction of ventricular tachycardia in nonsustained ventricular
      tachycardia after myocardial infarction and the usefulness of the signal-averaged
      electrocardiogram.
AB  - Assessment of the implications of clinical and noninvasive variables, including
      the results of signal-averaged electrocardiography, was performed > or = 3 weeks
      after myocardial infarction in 57 patients with nonsustained ventricular
      tachycardia (VT) who underwent programmed ventricular stimulation to guide
      antiarrhythmic therapy. The clinical and noninvasive parameters assessed included
      ages, left ventricular ejection fractions, sites of infarction, presence of
      akinetic or dyskinetic left ventricular segments, history of syncope, history of
      coronary artery bypass surgery, and presence or absence of late potentials from
      signal-averaged electrocardiography. Other than the presence of late potentials,
      no clinical or noninvasive parameters identified such persons with a
      significantly higher likelihood of inducible VT. When assessed as positive if 1
      or more variables were abnormal, 16 of 16 (100%) patients with versus 17 of 41
      without inducible VT had late potentials (p < 0.002). With more stringent
      criteria required (defined as prolongation of the QRS vector complex duration and
      low root-mean-square voltage of the terminal 40 ms of the vector complex) 8 of 16
      patients (50%) with and 4 of 41 (10%) without inducible VT had late potentials
      recorded (p < 0.002). Thus, the signal-averaged electrocardiogram may enable
      identification of persons with nonsustained VT after myocardial infarction who
      are most likely to have VT induced at programmed ventricular stimulation.

PMID- 8256705
TI  - Evaluation of edrophonium as a provocative agent for vasovagal syncope during
      head-up tilt-table testing.
AB  - Vasovagal syncope after head-up tilting is thought to be secondary to a complex,
      neurally-mediated reflex with both vasodepressor and cardioinhibitory efferent
      components. The efficacy of edrophonium, an acetylcholinesterase inhibitor, as a
      provocative agent for triggering syncope during head-up tilt testing was
      evaluated. Forty-five consecutive patients (22 female and 23 male) with history
      of recurrent unexplained syncope received edrophonium (10 mg intravenous) after
      30 minutes of 60 degrees head-up tilting alone. Twenty normal control subjects (9
      female and 11 male) were tested with head-up tilt testing and edrophonium.
      Syncope was induced in 19 of 45 patients with the diagnosis of unexplained
      syncope. In 9 patients who developed syncope with head-up tilting alone, the
      predominant hemodynamic finding was marked vasodepression. In contrast, in 10
      patients who developed syncope only after head-up tilting and edrophonium, the
      predominant hemodynamic findings were marked vasodepression and bradycardia.
      Syncope was induced in 1 of 20 normal subjects after head-up tilting and
      edrophonium. There was no long-term complication from using edrophonium. It is
      concluded that head-up tilt testing with edrophonium: (1) significantly increases
      the identification of patients with vasovagal syncope, (2) may be particularly
      useful when provocation with isoproterenol is undesirable, and (3) may be an
      effective method to help differentiate patients with a significant reflex
      cardioinhibitory component from those with a predominantly reflex vasodepressor
      component.

PMID- 8256706
TI  - Usefulness of electrophysiologic studies for new-onset sustained ventricular
      tachyarrhythmias shortly after coronary artery bypass grafting.
AB  - We retrospectively studied a group of 17 patients who developed life-threatening
      ventricular tachyarrhythmias shortly after coronary artery bypass grafting. The
      initial clinical event was sustained monomorphic ventricular tachycardia (VT) in
      15 and ventricular fibrillation (VF) in 2, occurring at an average of 3.6 days
      postoperatively. All patients underwent electrophysiologic testing, with
      sustained monomorphic tachyarrhythmias inducible in 7. Three early deaths
      occurred after this initial evaluation. Among the 9 survivors with nonsustained,
      nonclinical or noninducible VT, 4 received no antiarrhythmic therapy and remained
      free of recurrence, whereas of the 5 that received drugs, implantable
      defibrillators, or both, 2 had spontaneous recurrence. For the surviving subgroup
      with inducible monomorphic VT, serial drug testing culminated in maintenance
      therapy with class IA agents or amiodarone, whereas defibrillators were also
      implanted in 3 patients. Overall, recurrence of life-threatening tachyarrhythmias
      beyond the immediate postoperative period was seen in 40% of patients with
      monomorphic clinical tachycardias and inducible sustained monomorphic VT.
      Ventricular tachyarrhythmias appearing shortly after cardiac surgery demonstrate
      significant chronicity and resistance to antiarrhythmic drug therapy, while
      statistically significant predictors of inducibility or their recurrence remain
      undefined.

PMID- 8256707
TI  - Rehospitalization in surviving patients of out-of-hospital ventricular
      fibrillation (the CASCADE Study). Cardiac Arrest in Seattle: Conventional
      Amiodarone Drug Evaluation.
AB  - Surviving patients of out-of-hospital ventricular fibrillation (VF) often need
      rehospitalization after initial hospital discharge, but little is known regarding
      the frequency of or reasons for rehospitalization. Rehospitalization was examined
      in 224 patients enrolled in the Cardiac Arrest in Seattle: Conventional
      Amiodarone Drug Evaluation (CASCADE) study, a randomized clinical trial comparing
      amiodarone with other antiarrhythmic drug therapy in survivors of out-of-hospital
      VF. The annual rate of rehospitalization was 79/100 patients/year; 168 of 224
      patients (75%) were hospitalized at least once before censoring or cardiac
      mortality. Baseline left ventricular ejection fraction was significantly lower in
      patients who were rehospitalized. Rehospitalization rates were lower in patients
      randomized to amiodarone therapy and in those with the automatic implantable
      cardioverter-defibrillator, although neither difference was statistically
      significant. However, length of stay for the first rehospitalization was shorter
      for patients with automatic implantable cardioverter-defibrillators (p = 0.005).
      More than 50% of patients were rehospitalized in the first year after enrollment;
      65% with ejection fractions < or = 0.3 were rehospitalized in the first year.
      Rehospitalization was a frequent occurrence for surviving patients of out-of
      hospital VF, particularly in those with low ejection fractions.

PMID- 8256708
TI  - Effects of sustained-release isradipine on left ventricular anatomy and function
      in systemic hypertension.
AB  - With use of digitized M-mode echocardiograms and 24-hour noninvasive ambulatory
      blood pressure (BP) monitoring, the effects of chronic treatment with sustained
      release isradipine on left ventricular (LV) morphology and function in
      hypertensive patients were evaluated. We selected 12 patients with LV hypertrophy
      and normal LV diastolic diameter. Echocardiograms and 24-hour BP monitoring were
      performed after 2 weeks of placebo and after 6 months of oral treatment with
      sustained-release isradipine (5 mg once daily). Therapy significantly reduced BP
      without changes in heart rate. LV mass decreased in all patients and peak
      lengthening rate of LV diameter, index of diastolic function, increased in all,
      with normalization in 7 of the 9 with basal diastolic impairment. Peak shortening
      rate of LV diameter, index of systolic function, was normal in all patients at
      basal evaluation and did not change after therapy. Reduction in LV mass
      significantly (p < 0.05) correlated with the decrease in average 24-hour and
      daytime systolic and diastolic BP. Sustained-release isradipine administered once
      daily is an effective antihypertensive agent; the drug also induces regression of
      LV hypertrophy, with significant improvement in LV diastolic function and no
      deterioration in systolic function.

PMID- 8256709
TI  - Which physical factors determine tricuspid regurgitation jet area in the clinical
      setting?
AB  - The visual assessment of jet area has become the most common method used in daily
      clinic practice to evaluate valvular regurgitation. Despite the high prevalence
      of tricuspid regurgitation, however, few studies have systematically compared TR
      jet areas with a quantitative standard. To evaluate this, 40 patients in sinus
      rhythm with tricuspid regurgitation were analyzed: 16 with centrally directed
      free jets and 24 with impinging wall jets. The size of the maximal planimetered
      color jet area (cm2) was compared with parameters derived using the pulsed
      Doppler 2-dimensional echocardiographic method: regurgitant fraction and the flow
      convergence method (peak flow rate, effective regurgitant orifice area and
      momentum). Mean tricuspid regurgitant fraction averaged 33 +/- 15%, peak flow
      rate 76 +/- 54 cm3/s, effective regurgitant orifice area 27 +/- 21 mm2 and
      momentum 21,717 +/- 15,014 cm4/s2. An average of 4-chamber, and long- and short
      axis areas in free jets correlated well with regurgitant fraction (r = 0.81, p <
      0.001), better with peak flow rate (r = 0.94, p < 0.001), effective regurgitant
      orifice (r = 0.92, p < 0.001) and momentum (r = 0.94, p < 0.001). The correlation
      was worse, but still significant, in wall jets. For the same peak flow rate, wall
      jets were 75% of the size of a corresponding free jet. Jet area measurement is a
      good semiquantitative tool to measure tricuspid regurgitation in free jets, which
      correlates well with regurgitant fraction and better with new parameters
      available from analysis of the proximal acceleration field. In patients with
      eccentrically directed wall jets the correlation with planimetered jet area was
      worse, but still significant.

PMID- 8256710
TI  - Usefulness of pulmonary venous flow pattern and maximal mosaic jet area detected
      by transesophageal echocardiography in assessing the severity of mitral
      regurgitation.
AB  - Pulmonary venous flow pattern detected by transesophageal echocardiography (TEE)
      has been reported to be a good marker of mitral regurgitation (MR) severity. In
      89 patients with MR detected by TEE, both pulmonary venous flow pattern and
      maximal mosaic jet area were recorded for evaluating the severity of MR. Cardiac
      catheterization was performed in all patients for grading the severity of MR.
      Systolic reversed flow in pulmonary veins was a good marker for angiographic
      grade 3 or 4 MR with a sensitivity of 97% (33 of 34) and specificity of 95% (52
      of 55). Maximal mosaic jet area had a good correlation with the grading of MR (r
      = 0.79). When a maximal mosaic jet area of > 6 cm2 was used to detect grade 3 or
      4 MR, the sensitivity and specificity were lower than those of the systolic
      reversed flow (sensitivity 82 vs 97%, p = 0.073; specificity 80 vs 95%, p =
      0.013). The accuracy of systolic reversed flow was not influenced by the cardiac
      rhythm or jet eccentricity. However, the sensitivity of maximal mosaic jet area
      was lower in patients with an eccentric jet than in patients with a central jet
      (67 vs 95%, p = 0.046). In conclusion, systolic reversed flow in pulmonary veins
      detected by TEE is better than the maximal mosaic jet area in detecting grade 3
      or 4 MR, especially in patients with eccentric jet.

PMID- 8256711
TI  - Do patients with neurally mediated syncope have augmented vagal tone?

PMID- 8256712
TI  - Clinical and morphologic features of mitral valve prolapse in octogenarians.

PMID- 8256713
TI  - Non-thoracotomy closure of persistent ductus arteriosus beyond age 60 years.

PMID- 8256714
TI  - Mechanism of pericardial window creation by balloon pericardiotomy.

PMID- 8256715
TI  - Safety and cost of outpatient radiofrequency ablation of the slow pathway in
      patients with atrioventricular nodal reentrant tachycardia.

PMID- 8256716
TI  - Abnormal hemodynamic response to Valsalva maneuver in mitral stenosis.

PMID- 8256717
TI  - Usefulness of prolonged prostaglandin infusion in neonates with Ebstein's
      anomaly.

PMID- 8256718
TI  - How many patients with acute dissection of the thoracic aorta would erroneously
      receive thrombolytic therapy based on the electrocardiographic findings on
      admission?

PMID- 8256719
TI  - Physician use of transesophageal echocardiography varies with time after
      introduction into a hospital setting.

PMID- 8256720
TI  - Use of Doppler-derived left ventricular time intervals for noninvasive assessment
      of systolic function.

PMID- 8256721
TI  - Noninvasive estimation of coronary flow reserve by transesophageal Doppler
      measurement of coronary sinus flow.

PMID- 8256722
TI  - Usefulness of transesophageal echocardiography to screen for left atrial thrombus
      before elective cardioversion for atrial fibrillation.

PMID- 8256723
TI  - Usefulness of repeat coronary angiography 24 hours after successful balloon
      angioplasty to evaluate early luminal deterioration and facilitate quantitative
      analysis.
AB  - Because of the unavoidable occurrence of vessel disruption after successful
      coronary balloon angioplasty, the reliability of quantitative angiographic
      analysis in that setting has been questioned. For this reason and the suggested
      occurrence of delayed elastic recoil, repeat angiography at 24 hours has been
      advocated in clinical interventional trials. In this study, these issues are
      confronted by performing comprehensive quantitative analysis (Cardiovascular
      Angiographic Analysis System) of coronary angiograms, acquired in multiple
      identical projections immediately after and 24 hours after angioplasty, in 102
      patients with 110 successfully dilated lesions. Vasomotion was controlled by
      intracoronary nitrate before angiography and all patients were fully
      anticoagulated (activated partial thromboplastin time 85 to 120 seconds) for > 24
      hours. Paired Student's t tests applied to angiographic measurements revealed
      that there was no significant deterioration in minimal luminal diameter or cross
      sectional area from immediately after angioplasty to 24 hours later. It can thus
      be inferred that there is no phenomenon of delayed elastic recoil, at least
      during this time period. Measurement accuracy and precision of the Cardiovascular
      Angiographic Analysis System from the postangioplasty angiogram are highly
      acceptable, at < 0.01 and +/- 0.20 mm, respectively. Therefore, it is concluded
      that routine repeat 24-hour angiography is not indicated after successful
      angioplasty. A highly significant increase (p < 0.001) in reference diameter
      (+0.11 +/- 0.18 mm) was responsible for the apparent increase in percent diameter
      stenosis (2.4 +/- 7%), a finding that demonstrates the potential for error by
      selective application of percent diameter stenosis measurements alone.
      Preferential use of absolute luminal measurements is thus strongly recommended
      for clinical trials with angiographic monitoring.

PMID- 8256724
TI  - Comparison of results of coronary angioplasty during acute myocardial infarction
      with and without previous coronary bypass surgery.
AB  - Six hundred one consecutive patients undergoing reperfusion within 6 hours of
      acute myocardial infarction were studied with regard to impact of previous
      coronary artery bypass grafting (CABG) on direct coronary angioplasty performance
      and results. Forty-nine patients (8%) had previously undergone CABG, whereas 552
      (92%) had not. Direct angioplasty was used for reperfusion in 35 patients (71%)
      in the CABG group, and in 258 (47%) in the non-CABG group (p < 0.01). No
      significant differences between these groups were noted with regard to gender,
      age, infarction site, time to reperfusion or angioplasty success (34 of 35 CABG
      patients [97%] vs 236 of 258 non-CABG patients [92%]). CABG patients were more
      likely to have had previous infarction (17 of 35 [49%] vs 35 of 258 [14%] [p <
      0.001]), multivessel disease (34 of 35 [97%] vs 127 of 258 [49%] [p < 0.001]) and
      lower mean ejection fraction (0.36 +/- 0.13 vs 0.46 +/- 0.12, p < 0.001). Over a
      mean follow-up of 151 weeks, 24 patients (69%) in the CABG group were restudied
      versus 112 (43%) in the non-CABG group (p < 0.01). Restenosis occurred in 14
      patients (40%) in the CABG group versus 58 (22%) in the group without previous
      CABG (p = 0.04). In the CABG group, restenosis occurred significantly more often
      in saphenous vein grafts than in native vessels (12 of 17 [71%] vs 2 of 11 [18%]
      [p < 0.02]). There was no significant difference in the overall performance of
      repeat angioplasty between the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256725
TI  - Effect of percutaneous transluminal coronary angioplasty on circulating
      endothelin levels.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is frequently associated
      with vasoconstriction involving large vessels as well as microcirculation, but
      the potential mechanisms remain poorly defined. In this study, we tested the
      hypothesis that endothelial disruption during PTCA is associated with an increase
      in circulating levels of endothelin, a potent endothelium-derived vasoconstrictor
      peptide. Circulating levels of endothelin and other potential vasoactive
      mediators such as atrial natriuretic factor, epinephrine and norepinephrine were
      measured immediately before and after PTCA in 23 patients with coronary artery
      disease. Although there was no change in the endothelin levels after angiography
      alone (43 +/- 5 vs 44 +/- 7 pg/ml, p = 0.5), there was a significant increase
      after PTCA (32 +/- 8 to 37 +/- 10 pg/ml, p < 0.005). The increase in endothelin
      was associated with a significant increase in atrial natriuretic factor (78 +/-
      57 to 129 +/- 131 ng/ml, p = 0.01) and a decrease in epinephrine and
      norepinephrine levels (111 +/- 64 to 59 +/- 36 pg/ml, p = 0.005, and 1,131 +/-
      500 to 811 +/- 311 pg/ml, p = 0.003, respectively). Circulating levels of
      endothelin did not correlate with the percent coronary stenosis before or after
      PTCA or the presence or absence of angiographically visible thrombus. These
      findings suggest that endothelial injury during PTCA may be associated with
      increased circulating levels of endothelin and its counter-regulatory hormone,
      atrial natriuretic factor, and also with a reciprocal decrease in epinephrine and
      norepinephrine levels. Thus, these humoral changes may modulate changes in
      coronary vascular tone after PTCA.

PMID- 8256726
TI  - Usefulness and tolerability of hirulog, a direct thrombin-inhibitor, in unstable
      angina pectoris.
AB  - In an open-label pilot study of 20 patients with unstable angina (Braunwald class
      I-IIIB), hirulog was administered as a continuous intravenous infusion for 5 days
      in a dose of 0.2 mg/kg/hour to produce an activated partial thromboplastin time
      of approximately 200% of control. The primary end points of the study were:
      death, development of a transmural myocardial infarction, and intractable angina
      needing interventions such as an intraaortic balloon pump insertion, angioplasty
      and surgery. The secondary end points were the presence of an intracoronary
      thrombus detected on angiography and hemorrhagic complications during therapy.
      There was no death or transmural infarction in this study cohort; however, 1
      patient developed intractable angina. Intracoronary thrombus was documented in 2
      patients. Infusion of hirulog resulted in a steady prolongation of the activated
      partial thromboplastin time without any hemorrhagic or other adverse effect.
      Hirulog appears to be an effective antithrombotic agent that is tolerated well
      and may have advantages over heparin in the management of patients with unstable
      angina.

PMID- 8256727
TI  - Anger report predicts coronary artery vasomotor response to mental stress in
      atherosclerotic segments.
AB  - To determine the effects of anger on coronary artery vasoconstriction, 12
      patients with symptomatic myocardial ischemia were studied during cardiac
      catheterization. During catheterization, the patients were asked to recall a
      recent event that had produced anger. One narrowed and 2 non-narrowed arterial
      segments were selected using predetermined criteria. Patients also completed
      various self-report measurements upon entering the catheterization laboratory
      before any procedures, after completion of the clinical angiogram and after the
      anger recall stressor. There was a significant increase in subject reports of
      anger (F[1,6] = 21.94, p < 0.01) and arousal (F [2,6] = 5.49, p < 0.05) during
      the anger stressor. There were no significant changes in heart rate, systolic or
      diastolic blood pressure, or heart rate x systolic blood pressure product during
      the anger stressor. A total of 27 arterial segments (9 narrowed and 18 non
      narrowed) were selected and analyzed using quantitative angiographic techniques.
      Repeated-measures analysis of variance (baseline vs anger stressor) found no
      significant group differences with regard to changes in arterial diameter between
      conditions or among segments. Reported anger was significantly correlated with a
      decrease in both mean (r = -0.76, p < 0.05) and minimal (r = -0.82, p < 0.05)
      diameter changes in narrowed arteries. Vasoconstriction only occurred with high
      levels of anger. There were no significant correlations between anger report and
      diameter change in non-narrowed arteries. Thus, anger may produce coronary
      vasoconstriction in previously narrowed coronary arteries.

PMID- 8256729
TI  - Clinical and angiographic prediction of myocardial infarction and recurrence of
      severe angina during a five-year follow-up after coronary artery bypass grafting.
AB  - In a prospective, angiographically controlled study, 339 consecutive patients
      were examined to evaluate the pre-, peri- and postoperative risk factors for
      occurrence of myocardial infarction, and recurrence of severe angina during 5
      years after coronary artery bypass grafting (CABG). The incidence of myocardial
      infarction was 6% and the recurrence of severe angina 13%. No pre- or
      perioperative variable could predict the occurrence of myocardial infarction.
      Postoperative ejection fraction was significantly lower in patients with than
      without myocardial infarction (58 +/- 10% vs 50 +/- 11%; p < 0.001), and the Cox
      proportional-hazards method showed a low postoperative ejection fraction to be
      the only significant risk factor for the occurrence of myocardial infarction (p =
      0.02). Patients with a recurrence of severe angina had higher blood total
      cholesterol concentrations (7.7 +/- 1.4 vs 7.0 +/- 1.3 mmol/liter; p < 0.05) and
      triglyceride levels (2.7 mmol/l +/- 1.5 vs 2.0 +/- 1.0 mmol/liter; p < 0.01) than
      did those without angina, and also more often had > or = 1 occluded bypass graft
      3 months after CABG (p < 0.05). No other pre- or postoperative variable could
      predict the recurrence of angina. Both total blood cholesterol concentration and
      triglyceride level were significant predictors of the risk of recurrent severe
      angina by the Cox proportional-hazards method (p = 0.01 and 0.03, respectively).
      Thus, reduced ejection fraction is a risk factor for subsequent myocardial
      infarction, whereas blood lipid abnormalities predict the recurrence of severe
      angina during the 5 years after CABG.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256728
TI  - Immediate and long-term prognostic significance of a first anterior versus first
      inferior wall Q-wave acute myocardial infarction. Secondary Prevention
      Reinfarction Israeli Nifedipine Trial (SPRINT) Study Group.
AB  - Of 3,981 patients with a first Q-wave acute myocardial infarction (AMI), 1,929
      (48%) had an anterior and 1,724 (43%) an inferior wall AMI. These 2 groups were
      well-matched with respect to age, gender and relevant history. The in-hospital
      mortality rate was 18%, and the 1- and 5-year post-discharge mortality rates were
      9 and 25%, respectively, in patients with anterior wall AMI compared with the
      corresponding rates of 11, 6 and 19% in those with inferior wall AMI (p < 0.0001
      for each category). The frequency of recurrent nonfatal AMI in the year after the
      index AMI was 8% in the patients with anterior wall AMI compared with 4% in those
      with inferior wall AMI (p < 0.0001). By multiple logistic regression analysis of
      events, anterior wall AMI was an independent predictor of in-hospital mortality
      only. The findings indicate that the anatomic location of a Q-wave AMI influences
      immediate and short-term survival of patients with a first Q-wave AMI.

PMID- 8256730
TI  - Site of myocardial ischemia as a determinant of postexercise blood pressure and
      heart rate response in coronary artery disease.
AB  - Forty patients with coronary artery disease and 15 normal subjects (group C) were
      studied to assess the influence of the site of stress-induced myocardial ischemia
      on cardiovascular response after exercise. Patients were divided in 2 groups
      according to myocardial thallium-201 scintigraphy: those with an anteroseptal
      reversible perfusion defect (group A; n = 24), and those with an inferoposterior
      reversible perfusion defect (group I; n = 16). All patients underwent serial
      bicycle exercise stress tests. The first 2 stress tests were interrupted when 0.1
      mV of ST-segment depression was achieved (2,000 to 2,500 kg-m); a third test was
      stopped before the onset of ischemia (1,500 kg-m). Normal subjects performed
      stress tests at comparable work loads. At ischemic threshold, there was no
      difference in ejection fraction between groups A (65.5%) and I (67.3%). Mean
      values and recovery ratios of heart rate and systolic blood pressure were
      significantly higher in group A than in C and I during the recovery period of the
      2,000 to 2,500 kg-m stress test. In contrast, no significant difference was
      observed among the groups in the 1,500 kg-m stress test, and between groups I and
      C in any stress test. The data show that in patients with the same degree of
      stress-induced impairment of ventricular function, the anterior site of ischemia
      leads to persistently higher values of heart rate and blood pressure after
      exercise, which are likely due to an enhanced adrenergic discharge.

PMID- 8256731
TI  - Epidemiology of silent myocardial ischemia in asymptomatic middle-aged men (the
      ECCIS Project).
AB  - To evaluate the prevalence of type I silent myocardial ischemia and silent
      myocardial infarction, 4,842 men aged 40 to 59 years, identified in occupational
      samples in Florence and Rome, and free from major heart disease, severe illnesses
      and chest pain, underwent a 3-stage diagnostic procedure. The first stage
      included resting electrocardiogram, hyperventilation test, exercise
      electrocardiogram and 24-hour Holter electrocardiogram. The subjects who were
      suspected of having type 1 silent myocardial ischemia or previous silent
      infarction at the first stage (n = 439; 9.1%) were entered into the second stage,
      which included echocardiogram, thallium 201 scintigraphy in conjunction with
      exercise testing or dipyridamole test, exercise radionuclide ventriculography and
      ergonovine test. Three hundred eighty-seven men participated in the second stage;
      after the diagnostic procedures were performed, 104 men (2.1%) were still
      suspected of having type 1 silent myocardial ischemia or infarction on the basis
      of predefined criteria. Sixty-two men continued on into the third diagnostic
      workup including coronary angiography. The final diagnosis of type 1 silent
      myocardial ischemia or infarction was reached in 25 patients (prevalence 0.52%;
      adjusted estimate 0.89%). Of these 25, 19 had coronary atherosclerotic disease, 1
      had Kawasaki disease, 1 had coronary anomaly, 1 had induced focal coronary spasm,
      and 2 had normal coronary arteriograms despite the presence of unquestionable old
      myocardial infarction. Altogether, 6 patients with silent myocardial infarction
      were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256732
TI  - Comparison of electrophysiologic effects of quinidine and amiodarone in sustained
      ventricular tachyarrhythmias associated with coronary artery disease.
AB  - Fifteen patients with spontaneous ventricular tachyarrhythmias underwent
      electrophysiologic studies at baseline and during therapy with quinidine and
      amiodarone. In 9, ventricular tachycardia (VT) with a similar QRS morphology was
      induced with quinidine, amiodarone and under the control state. Both quinidine
      and amiodarone significantly increased QRS duration and the VT cycle length.
      Amiodarone increased the VT cycle length more than quinidine (85 vs 121 ms, p <
      0.05). Amiodarone increased the percent QRS duration (during sinus rhythm,
      ventricular pacing and VT) significantly less than percent VT cycle length,
      whereas quinidine did so only at slow rates (at faster rates the percent increase
      in QRS duration is not different from the percent increase in VT cycle length).
      The percent increase in QRS duration produced by quinidine correlated
      significantly with the percent increase in VT cycle length (the best correlation
      was observed during pacing, r = 0.78). In contrast, no such significant
      correlations were obtained for amiodarone. Thus, amiodarone prolongs VT cycle
      length more than quinidine (at the doses used). The effects of quinidine on
      conduction in tissue mostly unrelated to tachycardia origin predict effects in
      the tachycardia cycle length. In contrast, the effects of amiodarone on the
      latter are more intense but not predicted by those on tissue unrelated to the
      tachycardia origin.

PMID- 8256733
TI  - Oral amiodarone loading for the rapid treatment of frequent, refractory,
      sustained ventricular arrhythmias associated with coronary artery disease.
AB  - To evaluate the efficacy and safety of oral amiodarone in the treatment of
      recurrent, sustained, refractory ventricular arrhythmias, rapid high-dose oral
      loading was used to treat 12 critically ill patients with frequent, sometimes
      incessant, sustained ventricular arrhythmias refractory to 2 to 6 antiarrhythmic
      agents. Presenting arrhythmias included sustained monomorphic ventricular
      tachycardia and ventricular fibrillation associated with cardiac arrests in 6
      patients. Patients experienced 2 to 10 episodes (mean 5 +/- 2) of sustained
      ventricular arrhythmias over a mean period of 6.2 +/- 5.0 days (range 1 to 14)
      before oral amiodarone was initiated at 1,200 to 1,400 mg/day. This included at
      least 1 to 4 episodes (mean 2.2 +/- 1.1) within 24 hours before amiodarone. One
      to 4 antiarrhythmic drugs were administered concurrently during amiodarone
      loading. Sustained ventricular arrhythmias no longer occurred after a mean of 5.2
      days (range 1 to 22) with amiodarone. Arrhythmias were controlled in 4 patients
      within 24 hours, 5 patients within 48 hours, 7 patients within 4 days and 10
      patients within 6 days. Patients experienced a mean of 0.6 +/- 0.8 episodes
      within 24 hours after amiodarone. Nine patients survived to hospital discharge.
      No patient had significant adverse effects during high-dose loading. In
      conclusion, high-dose oral amiodarone loading, when added to previously
      unsuccessful conventional antiarrhythmic therapy, is safe and often rapidly
      effective for at least short-term control of frequent, refractory, sustained
      ventricular arrhythmias.

PMID- 8256734
TI  - Serial electropharmacologic studies in patients with ischemic heart disease and
      sustained ventricular tachyarrhythmias: when is drug testing sufficient?
AB  - Serial testing of antiarrhythmic drugs by programmed electrical stimulation can
      be costly in time, expense and risk. The purpose of this study was to evaluate
      the results of serial electropharmacologic tests for similarities that might
      obviate the need for protracted drug testing. Serial electropharmacologic testing
      was performed in 283 patients with coronary artery disease and clinical sustained
      ventricular tachycardia (VT) or fibrillation (VF). Drug tests were defined as
      concordant if sustained VT or VF could be consistently induced, or failed to be
      consistently induced during all such trials in a given patient. The following
      drugs were included for testing: procainamide, quinidine and disopyramide (class
      IA); phenytoin, mexiletine and tocainide (class IB); and flecainide and encainide
      (class IC). All patients were serially tested with > or = 2 (mean and median, 3)
      antiarrhythmic agents regardless of results from drug-free testing or initial
      acute drug testing. Overall, the results of serial drug trials directed by
      programmed stimulation were concordant in more than two thirds of patients.
      Concordance was comparably high whether patients were serially tested with drugs
      within the same antiarrhythmic class, or with drugs from differing classes, and
      was not related to patients' clinical or electrophysiologic characteristics.
      Protracted serial electropharmacologic testing does not appear necessary for
      predicting successful or unsuccessful antiarrhythmic drug therapy in survivors of
      clinical VT or VF. Single drug testing can identify most patients whose
      arrhythmia will or will not respond to medications.

PMID- 8256735
TI  - A randomized comparison of the right- and left-sided approaches to ablation of
      the atrioventricular junction.
AB  - Radiofrequency ablation of the atrioventricular (AV) junction may be performed
      using either a right- or left-sided approach. This study prospectively compared
      the left-sided approach with persistent attempts from the right side in patients
      in whom initial radiofrequency applications on the right side were unsuccessful.
      Twenty-one of 54 patients did not have complete AV block induced after 3 right
      sided radiofrequency applications. These 21 patients were randomly assigned to
      undergo either the left-sided approach (n = 10) or to undergo additional attempts
      from the right side (n = 11). The right-sided approach was performed by
      positioning the ablation catheter to record the largest possible atrial and His
      bundle electrograms. The left-sided approach was performed by positioning the
      ablation catheter along the left ventricular septum, where a His bundle potential
      was recorded. If either approach was not successful after an additional 17
      radiofrequency applications, the alternative approach was then used. The AV
      junction was successfully ablated in all 10 patients randomized to the left-sided
      approach, but in only 6 of 11 patients randomized to persistent right-sided
      attempts (p < 0.05). The 5 patients in whom the AV junction was not successfully
      ablated using the right-sided approach underwent the left-sided approach and had
      a successful outcome after a mean of 1.2 +/- 0.4 radiofrequency applications. The
      left-sided approach required significantly fewer radiofrequency applications
      after randomization than the right-sided approach (3 +/- 3.4 vs 11 +/- 7.6, p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256736
TI  - Transthoracic and transesophageal echocardiographic sizing of the aortic annulus
      to determine prosthesis size.
AB  - To assess the accuracy of 2-dimensional echocardiography versus transesophageal
      echocardiography (TEE) in predicting aortic annulus diameter, and to determine
      which part of the cardiac cycle should be used for measuring the size of the
      aortic valve prosthesis in patients undergoing aortic valve replacement, the
      aortic annulus was measured retrospectively in a blinded fashion in a group of 94
      patients who had undergone aortic valve replacement: 66 had preoperative
      transthoracic echocardiography (TTE), 69 had intraoperative TEE, and 41 had both.
      Accuracy of measurements was calculated by the mean biases (differences between
      annular size by echo and actual valve size chosen by intraoperative mechanical
      sizing of the aortic annulus). TTE was compared with TEE and end-diastolic (ED)
      measurements with end-systolic (ES) measurements. The mean biases +/- SD were 
      1.7 +/- 3.4 mm by TTE-ES versus -0.9 +/- 3.5 mm by TEE-ES measurements (p = NS),
      and +0.03 +/- 3 mm by TTE-ED versus +0.5 +/- 2.8 mm by TEE-ED (p = NS).
      Examination of the magnitudes of the biases gave the same result. ED measurements
      were found to have a smaller amount of bias than ES measurements, both by TTE and
      by TEE: -1.7 +/- 3.4 mm by TTE-ES versus +0.03 +/- 3 mm by TTE-ED (p = 0.0001)
      and -0.9 +/- 3.5 mm by TEE-ES versus +0.5 +/- 2.8 mm by TEE-ED (p = 0.0001).
      Examination of the magnitudes of the biases also gave the same result.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256737
TI  - Relation of left ventricular function to habitual alcohol consumption.
AB  - Left ventricular (LV) dysfunction is a frequent finding in chronic alcoholic
      subjects. LV function's relation to alcohol use in the general population, where
      low and moderate consumption predominate, was studied in this work. A random
      sample of 120 people born in 1954 was invited to participate in the study, and 93
      (42 men and 51 women) enrolled. Ethanol use was studied by 2-month daily
      recording of all alcoholic drinks; smoking and physical activity were quantified
      likewise, and salt intake by 7-day food records. Subsequently, subjects underwent
      an LV examination by M-mode echocardiography, and a transmitral flow velocity
      study by pulsed Doppler ultrasound. The relations of LV measurements to alcohol
      use were studied by multiple linear regression adjusting for sex, body size,
      blood pressure, heart rate, smoking, physical activity and dietary salt intake.
      No subject had clinical heart disease. The average daily ethanol consumption
      ranged from 0 to 1.2 g/kg of body weight (median 0.2). Statistically significant
      associations with square-root daily ethanol use were found for LV end-systolic
      diameter (regression coefficient [b] +/- SE 4.0 +/- 1.5 mm/square root of g/kg; p
      < 0.01), fractional shortening (b = -3.9 +/- 1.8%/square root of g/kg; p < 0.05),
      peak early transmitral velocity (b = -8.9 +/- 3.5 cm/s/square root of g/kg; p <
      0.05), and peak atrial transmitral velocity (b = -4.9 +/- 1.9 cm/s/square root of
      g/kg; p < 0.05). No interactions with sex were observed.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8256738
TI  - Assessment of flow profile of left anterior descending coronary artery in
      hypertrophic cardiomyopathy by transesophageal pulsed Doppler echocardiography.
AB  - This study assessed the flow velocity profiles of the left anterior descending
      coronary artery (LAD) in 7 patients with nonobstructive hypertrophic
      cardiomyopathy (HC) and in 6 normal subjects by transesophageal pulsed Doppler
      echocardiography, and evaluated their characteristics and the hemodynamic
      determinants. Systolic peak flow velocity of the LAD (7 +/- 30 cm/sec) was
      significantly lower in patients with HC than in normal subjects (34 +/- 11 cm/s,
      p < 0.05), and there was a significant inverse correlation between systolic peak
      flow velocity and the thickness of the ventricular septum (r = 0.81, p < 0.01).
      In 2 cases of HC with ventricular septal thickness of > 20 mm, a remarkable
      systolic reverse flow was observed in the LAD. However, there was no significant
      difference in diastolic peak flow velocity between HC and normal subjects. During
      early diastole, the acceleration time of LAD flow velocity was significantly
      prolonged (210 +/- 67 vs 95 +/- 15 ms, p < 0.01) and the acceleration rate was
      significantly decreased (3.6 +/- 2.0 vs 6.6 +/- 1.8 m/s2, p < 0.02) in patients
      with HC. The time constant of the left ventricular pressure decay was
      significantly prolonged in patients with HC (55 +/- 6 ms) compared with normal
      subjects (39 +/- 2 ms, p < 0.001). In HC, increased intramural perivascular
      pressure of the thickened ventricular septum during systole may be attributed to
      systolic LAD flow pattern. However, the early and mid-diastolic LAD flow pattern
      may be affected by impaired left ventricular relaxation.

PMID- 8256739
TI  - Long-term follow-up (9 to 20 years) after surgical closure of atrial septal
      defect at a young age.
AB  - To assess the long-term cardiac status after surgical closure of an atrial septal
      defect (ASD) at a young age, 104 of 135 children who consecutively underwent
      surgery (aged 0 to 14 years) at 1 institution between 1968 and 1980 participated
      in a follow-up study and underwent a complete cardiologic examination. Mean
      follow-up was 14.5 +/- 2.8 years. Most patients (87%) believed their health to be
      good or very good. At physical examination, all patients were in good health.
      Ninety-three patients (89%) were in sinus rhythm. Echocardiography showed that
      right ventricular dilatation was present in 27 patients (26%), 2 of whom had a
      residual ASD. Bicycle ergometry revealed that 88 patients (88%) had a normal
      exercise capacity. Both supraventricular and ventricular arrhythmias were
      observed in 67% of patients by 24-hour ambulatory electrocardiography, but only 3
      (3%) had received antiarrhythmic medication, and 4 (4%) had needed a pacemaker.
      In the group of patients with right ventricular dilatation, the exercise capacity
      and prevalence of arrhythmias did not differ significantly from those in the
      group with a normal sized right ventricule. The outcome in patients with a
      secundum-type ASD was not different from that of those with a sinus venosus-type
      ASD. The finding of anatomic, functional or electrophysiologic abnormalities was
      not associated with a longer duration of follow-up.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8256740
TI  - Magnetic resonance imaging of constant total heart volume and center of mass in
      patients with functional single ventricle before and after staged Fontan
      procedure.
AB  - It has been previously demonstrated that total heart volume (contents of
      pericardium) throughout the cardiac cycle varies by < 5% and location of center
      of mass by < 3 mm. The hypothesis has thus developed that for maximal efficiency,
      the heart should expend minimal energy in displacing extracardiac structures by
      maintaining a constant intracycle total heart volume and center of mass. This is
      achieved in the normal heart mainly by a piston-like movement of the
      atrioventricular valve plane toward the ventricular apex. As this has never been
      studied in the single ventricle heart or at various stages of Fontan
      reconstruction, it is conceivable that these patients may not exhibit the
      constancy of total heart volume and location of center of mass, which may lead to
      a poor outcome in some. The total heart volume and center of mass relationship
      was therefore evaluated in 25 children (0.4 to 237 months) with functional single
      ventricles at all stages of Fontan reconstruction using multiphase, multislice
      spin-echo or cine-magnetic resonance imaging. No significant difference was seen
      in variation between total heart volume and maximal volume between patients
      before bilateral cavopulmonary anastomosis (hemiFontan) (5.1 +/- 2.9%), after
      hemiFontan (3.6 +/- 1.6%) and after Fontan (8.2 +/- 7.7%); however, in 4 of 10, 1
      of 8 and 5 of 7 patients, respectively, the total heart volume varied by < 5%.
      Across surgical subgroups, significant differences were found in the center of
      mass displacement (total, anteroposterior and superoinferior planes) but not in
      directionality of displacement.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256741
TI  - Cardiopulmonary performance at rest and exercise after repair of total anomalous
      pulmonary venous connection.
AB  - Although long-term evaluations of patients after repair of total anomalous
      pulmonary venous connection have generally shown them to be clinically
      asymptomatic, assessment of their cardiovascular and pulmonary systems have been
      limited. Residual cardiopulmonary abnormalities undetected at rest may result in
      impaired function during exercise. To evaluate this hypothesis 9 patients
      underwent exercise testing after repair of total anomalous pulmonary venous
      connection. Pulmonary function testing was performed before exercise. Patients
      exercised using a 1-minute incremental bicycle or treadmill protocol monitoring
      heart rate, oxygen consumption, carbon dioxide production and minute ventilation.
      Compared with healthy children, the study patients had reduced maximal oxygen
      consumption and reduced oxygen consumption at ventilatory anaerobic threshold.
      Chronotropic response was impaired in 5 patients. Resting pulmonary functions
      showed evidence of mild restrictive lung disease. Breathing reserve was within
      normal limits. It is concluded that (1) aerobic capacity is mildly reduced after
      repair of total anomalous pulmonary venous connection, (2) chronotropic
      impairment is a common occurrence, and (3) pulmonary testing suggests mild
      restrictive lung disease that does not compromise exercise performance.

PMID- 8256742
TI  - Usefulness of transesophageal echocardiography in unexplained cerebral ischemia.
AB  - Two-hundred seventy consecutive patients with "unexplained cerebral ischemia"
      were studied with transesophageal echocardiography to determine the value of this
      test in identifying potential cardiac sources of cerebral embolism. The findings
      of this group were compared with those of 772 consecutive patients undergoing
      transesophageal echocardiographic evaluation for indications other than cerebral
      ischemia. This study also examined this group of patients with unexplained
      cerebral ischemia to determine differences in relation to underlying cardiac
      rhythm and patient age. Intracardiac thrombus, atrial septal aneurysm, patent
      foramen ovale, spontaneous left atrial contrast and protruding debris in the
      thoracic aorta were found more often in patients with unexplained cerebral
      ischemia. Wall motion abnormalities of the left ventricle, as well as mild to
      moderate valvular lesions including mitral valve prolapse, were found to be
      similar in both groups. Spontaneous left atrial contrast, as well as mild to
      moderate valvular abnormalities, were found more often in patients with atrial
      fibrillation (22% of the group with unexplained cerebral ischemia). However, the
      presence of intracardiac thrombus was no more frequent in patients with atrial
      fibrillation than in those with normal sinus rhythm. Patients aged > 50 years
      were found to have atrial fibrillation and larger left atrial size more often
      than their younger cohorts, as well as a greater incidence of valvular
      abnormalities and left ventricular wall motion abnormalities. Mitral valve
      prolapse was seen more frequently in the younger cohort of patients.

PMID- 8256743
TI  - Hypothetical death rates of patients with implantable defibrillators remain very
      hypothetical.

PMID- 8256744
TI  - Stunning and angina.

PMID- 8256745
TI  - Improved methods for intracoronary Doppler flow velocity.

PMID- 8256746
TI  - Misplacements involving the ground (right leg) electrode.

PMID- 8256747
TI  - Nonsurgical treatment of membranous obstruction of the inferior vena cava by
      percutaneous Inoue balloon angioplasty.

PMID- 8256748
TI  - Relations of QTc prolongation on the electrocardiogram to torsades de pointes:
      definitions and mechanisms.
AB  - Antiarrhythmic drug-induced ventricular tachyarrhythmias have traditionally been
      identified on the basis of prolongation of the QT interval and the appearance of
      undulating peaks of sequential QRS complexes and T waves that give the
      tachycardia a "twisting" aspect (so-called torsades de pointes). It is now
      understood, however, that a precise lengthening of the QT interval is not a
      necessary or sufficient criterion for the development of torsades de pointes
      associated with drug therapy. Indeed, not all agents that have been linked with
      torsades de pointes cause significant lengthening of the QT interval. Moreover,
      sufficiently accurate determination of QT interval duration to judge a
      prolongation is confounded by a number of difficulties, including considerable
      intraindividual variability. It is possible that the development of abnormal
      giant U waves may be involved in the genesis of these tachyarrhythmias. Such U
      waves are believed to represent the summation of early afterdepolarizations
      occurring throughout the myocardium. The prepause ventricular rate determines the
      amplitude of the U wave, and larger U waves give rise to longer and faster runs
      of ventricular tachycardia. These arrhythmias tend to be self-perpetuating in a
      bigeminal feedback pattern. At present, our knowledge base about the relation of
      the QT interval and torsades de pointes is grossly incomplete. More basic and
      clinical data are required before hard clinical judgments can be made with any
      precision.

PMID- 8256749
TI  - How to measure the QT interval--what is normal?
AB  - The QT interval extends from the beginning of the QRS complex to the end of the T
      wave. Since the report of Jervell and Lange-Nielsen in 1957, it has been
      difficult to determine whether to measure a QT or a QU interval. U waves are more
      prominent in the left chest leads and less prominent in lead II, with the end of
      the T wave in lead II corresponding to the end of significant repolarization in
      any other lead. Therefore, by convention, lead II has been chosen to measure the
      QT interval. Numerous attempts at correction have been made, but Bazett's
      correction (QT/square root of RR) remains the current standard. In stable sinus
      rhythm, a QT interval corrected for heart rate (QTc) of > 0.44 sec is considered
      abnormal. In this study, in the presence of sinus arrhythmia, the QT interval
      following the shortest RR interval was > 0.46 sec in 98.4% of patients with the
      congenital long QT syndrome, but in only 3.8% of control subjects (p < 0.0001).
      Likewise, in the presence of sinus arrhythmia, the uncorrected QT interval varied
      by > 0.03 seconds in a 10-sec rhythm strip of lead II in 33% of long QT syndrome
      patients but in 0% of controls (p < 0.01). The QT interval varied depending on
      autonomic tone and state of wakefulness, being approximately 19 msec longer in
      sleeping patients with a heart rate of 60 beats/min than in awake patients with
      the same heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256750
TI  - Rate-corrected QT interval: techniques and limitations.
AB  - The duration of the QT interval on the surface electrocardiogram represents the
      time required for all ventricular depolarization and repolarization processes to
      occur. Among the many physiologic and pathologic factors that contribute to the
      QT interval, heart rate plays a major role. Several approaches have been used to
      correct the QT interval, all of which take into account the heart rate at which
      the interval is measured. The simplest and most common approach to correcting the
      QT interval is to divide its value by the square root of the preceding RR
      interval expressed in seconds, i.e., by using Bazett's formula. This calculation
      provides a corrected QT (QTc) interval that represents the QT interval normalized
      for a heart rate of 60 beats/min. However, several studies have shown that
      Bazett's correction formula is not optimal. Fridericia's cube-root formula has
      been shown to perform better in correcting the QT interval for heart rate. Other
      formulas require the measurement of several QT-RR pairs at various heart rates to
      obtain a reliable QTc interval and are therefore not easily usable. Any
      correction formula is likely to introduce an error in assessing the QTc interval.
      Although the importance of this error should not be minimized, the corrected QT
      interval remains useful in assessing the effects of drugs on the duration of
      repolarization. For this purpose, Fridericia's cube-root formula is preferable to
      Bazett's square-root formula.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256751
TI  - Measurement of the QT interval and the risk associated with QTc interval
      prolongation: a review.
AB  - The accurate measurement of the QT interval and its correction or adjustment for
      cycle length, age, and gender have been topics of increasing interest over the
      course of the past 70 years. The availability of digitized electrocardiographic
      recordings on large normal populations together with statistical adjustment for
      pertinent covariates has provided useful data for defining QT interval
      prolongation. Data from the International Long QT Syndrome Registry indicate that
      the probabilistic risk of developing malignant arrhythmias in patients with QT
      prolongation is exponentially related to the length of the QTc interval. The risk
      is further accentuated by the development of T-wave alternans, particularly at
      very prolonged QTc intervals.

PMID- 8256752
TI  - Variability of the QTc interval: impact on defining drug effect and low-frequency
      cardiac event.
AB  - Prolongation of the QT interval corrected for heart rate (QTc) can lead to the
      development of torsades de pointes, a life-threatening form of polymorphic
      ventricular tachycardia. However, the QTc interval duration exhibits a high
      degree of spontaneous variability and is not necessarily a direct predictor of
      the risk of torsades. This observation holds implications for the assessment of
      the potential proarrhythmic effects of noncardiac pharmacologic agents. To date,
      the antihistamine terfenadine is the only noncardiac drug that has undergone a
      comprehensive and systematic evaluation related to the consequences of its
      causing QTc prolongation. The results suggest that QTc prolongation resulting
      solely from terfenadine at clinical doses does not have an important impact on
      clinically relevant endpoints. The risk of serious ventricular arrhythmias with
      terfenadine using epidemiologic data is the same or less than that associated
      with traditional first-generation antihistamines. The risk of a clinical cardiac
      event (QTc prolongation, ventricular arrhythmias, syncope, or sudden death) with
      terfenadine is similar to that of other antihistamines. Factors associated with
      increased risk in patients taking terfenadine include significant liver disease,
      hypokalemia, overdose, and concomitant administration of ketoconazole-like agents
      or erythromycin; use of terfenadine is relatively contraindicated in these
      settings. No increased risk of serious arrhythmias has been confirmed in
      conjunction with the use of terfenadine in patients with cardiac disease.

PMID- 8256753
TI  - QT interval: a measure of drug action.
AB  - Historically, QT prolongation, occurring with or without drug therapy, has been
      considered primarily as a clinical marker for risk of arrhythmia. However, as
      understanding of cardiac repolarization improves and ability to measure
      accurately small changes in QT interval increases, the QT interval will be used
      as a marker for drug action as well. In addition, QT prolongation may prove to be
      a valuable tool for detecting and quantifying risk of arrhythmia due to drugs.
      This has been emphasized recently by the experience with terfenadine. Use of the
      QT interval as a marker for toxicity and efficacy will require sensitive and
      specific methods that are currently being developed and validated. The current
      methodologies for detecting small changes in the QT interval and the significance
      of those changes are discussed.

PMID- 8256754
TI  - Mechanisms and models to predict a QTc effect.
AB  - Prolongation of the QT interval with consequent ventricular tachyarrhythmias may
      arise in the context of bradycardia (pause dependent) or may reflect sympathetic
      imbalances (adrenergic dependent). The normal repolarization process of
      ventricular myocardial cells is not entirely synchronous; some cells recover
      early and some later, resulting in a normal heterogeneity in refractoriness among
      ventricular cells during the inscription of the T wave. If the normal
      heterogeneity in ventricular repolarization is increased, as can occur following
      administration of some class IA and class III antiarrhythmic agents, then the QT
      interval will be prolonged. All-or-none action potentials can be evoked only in
      cells that have repolarized to a critical membrane potential of about -60 mV.
      Thus, the late-recovering cells (which terminate the T wave) may still be
      refractory and incapable of generating propagated action potentials while the
      early-recovering cells (which initiate the T wave) are fully excitable. In normal
      hearts, the period between repolarization of the earliest and the latest cells is
      insufficient to allow even very premature ventricular beats that occur early
      during the T wave (R-on-T phenomenon) to precipitate a sustained tachyarrhythmia.
      When the recovery process among ventricular cells becomes more inhomogeneous,
      however, as in the prolonged QT syndrome, the accompanying increased
      heterogeneity in ventricular repolarization and refractoriness can lead to the
      development of malignant ventricular arrhythmias, including torsades de pointes.
      Any drug that increases the dispersion of the repolarization process may prolong
      the QT interval and raise the potential for arrhythmias.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8256755
TI  - Current status of class III antiarrhythmic drug therapy.
AB  - Studies in animal models, as well as clinical experience with amiodarone and
      sotalol, suggest that action potential prolongation may be a useful
      antiarrhythmic mode of action. A number of agents that produce this class III
      effect are currently under development. The single greatest liability for further
      development of this group of drugs is the occasional, and apparently
      unpredictable, development of exaggerated QT prolongation and polymorphic
      ventricular tachycardia (torsades de pointes). Available data suggest that QT
      interval prolongation is not a good indicator of whether or not a class III
      antiarrhythmic will suppress a target arrhythmia; however, exaggerated QT
      prolongation is a predictor of torsades de pointes. Further studies to delineate
      the mechanism underlying the development of torsades de pointes might lead to
      safer and more effective antiarrhythmic drugs.

PMID- 8256756
TI  - Is QT interval prolongation harmful? A regulatory perspective.
AB  - Drugs that prolong the QT interval may increase the risk of torsades de pointes,
      a potentially lethal ventricular arrhythmia. In recent years, spontaneous reports
      have highlighted these complications in patients receiving certain antihistamines
      (e.g., terfenadine or astemizole) or an agent for the treatment of incontinence
      (terodiline). Examination of these reports has revealed that hepatic disease or
      concomitant therapy with ketoconazole or macrolide antibiotics may increase the
      risk of QT prolongation or torsades in patients receiving terfenadine. In
      patients receiving astemizole, doses exceeding that recommended or concomitant
      therapy with ketoconazole or macrolide antibiotics have been implicated in the
      increased risk of these complications. With terodiline (which remains
      investigational in the United States), the risk of QT prolongation and torsades
      are of particular concern in the frail elderly, who are most likely to be treated
      with this agent. A possible explanation for the elevated risk may be marked
      increases in the elimination half-life and serum level of the drug in this group.
      The lessons learned from the experiences with these drugs hold implications for
      the future development of agents that prolong the QT interval and suggest the
      need for dose-response relation data and metabolic evaluations to define the
      subpopulations at particular risk.

PMID- 8256757
TI  - A viewpoint on drugs that prolong the QTc interval.
AB  - Insufficient evidence exists to suggest that prolongation of the QT interval
      corrected for heart rate (QTc) is necessarily beneficial. In all but life
      threatening situations, QTc prolongation resulting from pharmacologic agents must
      be considered a risk. Because dose-response relations for torsades de pointes
      cannot be established and because prolongation of the QTc interval is thought to
      precede the development of torsades, it is reasonable to assume that the QTc
      prolongation itself constitutes the marker of risk. An assessment of the relation
      between the dose of a given drug and its effect on the QTc interval will aid in
      making the judgment that the potential benefit outweighs the risk. Ideally, a
      drug should demonstrate as wide a safety margin as possible, as reflected in a
      large separation between the ED50 value associated with therapeutic benefit and
      that associated with QTc prolongation.

PMID- 8256758
TI  - Concomitant alpha-interferon and chemotherapy in advanced squamous cell carcinoma
      of the head and neck.
AB  - The combination of chemotherapy and interferons has been tested in several human
      tumors but, until now, no clinical data have been reported in head and neck
      cancer. At the Istituto Nazionale per la Ricerca sul Cancro of Genoa, 14 patients
      with previously treated SCC-HN underwent the following regimen: cisplatin, 20
      mg/m2/day, 5-fluorouracil, 200 mg/m2/day i.v. bolus and recombinant interferon
      alpha-2b (r-IFN-alpha-2b) (Intron-A, Shering-Plough), 3 MIU/day i.m., for 5
      consecutive days. Recombinant IFN-alpha-2b was also administered, at the same
      dosage, 3 times per week during the 2 weeks interval among cycles. Grade III-IV
      hematological toxicity was recorded in 43% of patients. Increasing fatigue,
      anorexia, and flu-like symptoms were experienced by most patients. For these
      reasons 9 of 14 patients needed a chemotherapy delay and a r-IFN-alpha-2b
      discontinuation. Therefore, due to the heavy toxicity observed, accural was
      terminated early. The overall response rate was 54% (31% CR, 23% PR). Among the 5
      patients who never delayed chemotherapy and discontinued r-IFN-alpha-2b, all but
      one responded. In conclusion, a synergistic activity between chemotherapy and r
      IFN-alpha-2b in head and neck cancer cannot be excluded, but, in our opinion,
      further investigations should consider less aggressive regimens and/or more
      selected patients.

PMID- 8256759
TI  - Evaluation of 45 degrees C hyperthermia and irradiation. I. Studies in a murine
      rhabdomyosarcoma model.
AB  - This report describes biologic experiments using transplanted RIF-1 tumors
      (diameter 0.5 or 1 cm) in C3H/He inbred mice (12 to 20 per treatment group) to
      compare the results with heat alone (43 degrees C for 60 minutes or 45 degrees C
      for 15 minutes, twice weekly via radiofrequency electrodes), irradiation alone
      (400 cGy twice weekly for a total of 4,000 cGy with 140 kVp x-rays), or a
      combination of both therapies. Animals receiving combined treatment had
      significantly greater complete regression than those treated with either therapy
      alone. Tumor regrowth curves were equivalent for 43 degrees C or 45 degrees C
      following irradiation. In tumors 0.5 cm in diameter the overall tumor cure rates
      were 17% for 43 degrees C for 60 minutes and 25% for 45 degrees C for 15 minutes
      with heat alone and 8% with irradiation alone; the combination of irradiation and
      heat at both temperatures yielded comparable complete cure rates (75 and 67%).
      With 1-cm tumors the corresponding cure rates were 0% with heat alone (either
      temperature), 5% for irradiation alone, 33% for irradiation and 43 degrees C
      heat, and 64% for irradiation and 45 degrees C heat (p = .3). Approximately 20%
      of the animals in the various groups developed moist or dry desquamation in the
      area treated, whereas 40 to 66% exhibited moist desquamation. There was a slight
      increase in this sequela (73%) for mice that received irradiation and 45 degrees
      C compared with 50% in mice treated with 43 degrees C, but the difference was not
      statistically different (p = .54). Experimental studies demonstrated equivalent
      efficacy of 10 hyperthermia sessions at 43 degrees C or 45 degrees C combined
      with irradiation. Caution must be exercised in the clinical application of
      thermal iso-effect heat dose concepts until further clinical trials have been
      performed and there is a better understanding of the time-temperature
      relationship.

PMID- 8256760
TI  - Evaluation of 45 degrees C hyperthermia and irradiation. II. A phase I clinical
      trial in humans by the Radiation Therapy Oncology Group.
AB  - This report describes the experience in 40 evaluable patients entered into a
      Radiation Therapy Oncology Group (RTOG) study to evaluate the feasibility of
      administering 45 degrees C for 15 minutes for superficial malignant lesions: 18
      patients (45%) tolerated only 1 heat session at 45 degrees C; 7 (17.5%), 2
      sessions; 4 (10%), 3 sessions; and 3 (7.5%) tolerated > or = 4 sessions. The
      overriding reason for discontinuing at 45 degrees C treatment was pain. Of the 40
      evaluable patients, 22 (55%) had complete tumor regression, and 8 (20%) had
      partial regression. Tumors < or = 3 cm in diameter had significantly better
      complete tumor response than lesions > 3 cm (85% vs 41%) (p = .02). We conclude
      that 45 degrees C heating is difficult to use in patients chiefly because of
      pain; this may be due in part to inadequacy of currently available external
      hyperthermia equipment. Caution must be exercised in the application of thermal
      isoeffect heat dose concepts in clinical practice until further trials have been
      performed and a better understanding of the time-temperature relationship is
      established.

PMID- 8256761
TI  - The reirradiation of recurrent bronchogenic carcinoma with external beam
      irradiation.
AB  - Symptomatic local failure following thoracic irradiation for bronchogenic
      carcinoma presents a clinical challenge to the Radiation Oncologist. We
      retrospectively evaluated the efficiency of reirradiation with external beam
      radiation of 30 patients. The median dose of initial irradiation was 6,000 cGy in
      6 weeks. The median time following initial irradiation to recurrence was 12
      months. The median dose of retreatment was 3,030 cGy in 3 weeks. Of the
      symptomatic patients, 88% and 70% subjectively responded to initial irradiation
      and to reirradiation, respectively. Retreatment toxicity included radiation
      esophagitis (6 patients), dry desquamation (4 patients), and symptomatic
      radiation pneumonitis (1 patient). Based on this study, doses of external beam
      radiation in the range of 2,000-3,000 cGy in 2 to 3 weeks appear safe and
      effective in reirradiating recurrent bronchogenic carcinoma.

PMID- 8256762
TI  - 14-Day continuous infusion of mitoxantrone in hormone-refractory metastatic
      adenocarcinoma of the prostate.
AB  - A dose-finding investigation was conducted with mitoxantrone administered as 14
      day continuous infusions to patients with hormone-refractory metastatic
      adenocarcinoma of the prostate. Fifteen men participated in four dosage groups:
      mitoxantrone 1.0, 1.25, 1.4, and 1.5 mg/m2/day; a treatment cycle was defined as
      a dose of mitoxantrone given over 2 weeks, followed by 2 weeks of monitoring
      prior to the next course. The patients received 1 to 10 courses, with the
      majority receiving 1 to 3. The maximum tolerated dose was 1.25 mg/m2/day for 14
      days of continuous infusion. Two patients discontinued treatment because of
      gastrointestinal effects. Most adverse clinical experiences were mild or moderate
      in intensity. A decrease in prostate-specific antigen (PSA) response was seen
      after one course in 6 of 14 patients who had PSA measurements. Stable disease was
      achieved in 40% of the evaluable patients, and some quality of life parameters
      improved. Further clinical trials with mitoxantrone are indicated in patients
      with prostatic cancer, especially in those who have had less previous treatment.

PMID- 8256763
TI  - Echinomycin in recurrent and metastatic endometrial carcinoma. A phase II trial
      of the Gynecologic Oncology Group.
AB  - Twenty-one evaluable patients with recurrent or metastatic endometrial carcinoma
      were treated with 1,500 micrograms/m2 of echinomycin every 3 weeks. All patients
      had received prior chemotherapy. There was one complete response (5%), 95%
      confidence interval for response is 0.9-22.7%. The major toxicity was nausea and
      vomiting which was moderate to severe in 42% of patients. Myelosuppression was
      minimal. Echinomycin, in this dose and schedule, displays minimal activity in
      patients with advanced endometrial carcinoma who have had prior chemotherapy.

PMID- 8256765
TI  - Intraoperative orthovoltage radiation therapy in the treatment of recurrent
      gynecologic malignancies.
AB  - A Phase I/II study was initiated to evaluate complications of orthovoltage
      intraoperative radiation therapy utilized in the treatment of patients with
      incompletely resected recurrent gynecologic malignancies. There were no osseous,
      vascular, neurologic, or ureteral complications. Of the 23 treated patients, 2
      patients (8.7%) had complications outside the treated area. Survival of patients
      treated with intraoperative radiation therapy was highest among patients treated
      to a field of < or = 3 cm in greatest diameter and a tumor thickness of < or = 1
      mm. A subgroup of patients (5) with microscopically positive margins following
      total pelvic exenteration demonstrated an absence of recurrence in the treated
      field. The role of intraoperative radiation therapy (IORT) in the treatment of
      recurrent and incompletely resectable gynecologic malignancies remains
      investigational.

PMID- 8256764
TI  - Circadian-timed combination doxorubicin-cisplatin chemotherapy for advanced
      endometrial carcinoma. A phase II study of the Gynecologic Oncology Group.
AB  - Patients with advanced or recurrent endometrial cancer of any cell type having
      measurable disease have been entered into this study to determine the
      effectiveness and toxicity of circadian-timed doxorubicin-cisplatin chemotherapy.
      This Phase II study involved no randomization with treatment initiated with
      doxorubicin 60 mg/m2 over 30 minutes at 6:00 a.m., followed by cisplatin 60 mg/m2
      over 30 minutes at 6:00 p.m. every 28 days. Treatment was continued for eight
      cycles or to a maximum tolerable doxorubicin dose of 480 mg/m2 for patients
      without progression. Thereafter, responders continued on cisplatin alone. A
      review of 30 evaluable patients showed 6 (20%) complete responses, 12 (40%)
      partial responses, and 7 (23%) with stable disease. The number of treatment
      courses ranged from 2 to 14 with a median of 6.5. the median white blood cell
      nadir for the 27 patients experiencing leukopenia was 1,600/mm3 (range: 300
      3,600/mm3) For the 16 patients experiencing thrombocytopenia the median nadir was
      48,500/mm3 (range: 8,000-138,000/mm3). There were no treatment-related deaths.
      Circadian-timed delivery of doxorubicin-cisplatin chemotherapy was reasonably
      well tolerated and demonstrated notable response rates in patients with advanced
      or recurrent endometrial carcinoma.

PMID- 8256766
TI  - Combined modality therapy for locally advanced penile squamous cell carcinoma.
AB  - We report here a patient who presented with locally advanced Jackson Stage IV
      penile squamous cell carcinoma who was managed with preoperative 5-fluorouracil,
      mitomycin C chemotherapy, and concurrent radiation therapy. He experienced an
      excellent partial response which allowed more limited surgery than would
      otherwise be indicated. He is still alive and well 5 years after completion of
      his treatment without side effects, local recurrence, or distant metastatic
      disease.

PMID- 8256767
TI  - A phase II trial of tricyclic nucleoside phosphate in patients with advanced
      squamous cell carcinoma of the cervix. A Gynecologic Oncology Group Study.
AB  - A Phase II trial of TCN-P was conducted in metastatic or recurrent squamous cell
      carcinoma of the cervix using a 5-day continuous infusion schedule. The starting
      dose was 35 mg/m2 x 5 days and courses were repeated every 6 weeks. Among 21
      evaluable patients, 2 responses were observed. One patient had a complete
      response for 19+ months. Another patient had a partial response for 5+ months,
      but developed symptomatic hypocalcemia, requiring discontinuation of the drug.
      Using this dose and schedule TCN-P appears to have limited activity in metastatic
      or recurrent squamous cell cancer of the cervix.

PMID- 8256768
TI  - T3 squamous cell carcinoma of the larynx treated by a split-course radiation
      protocol. A multiinstitutional study.
AB  - A retrospective multiinstitutional study was initiated analyzing patients with T3
      squamous cell carcinoma of the larynx, treated between 1975 and 1984 in eight
      Dutch head and neck cancer centers. In two institutions the treatment modalities
      used depended on the assessment of the response of the primary tumor to a first
      series of radiation. According to this split-course regime protocol, poor
      responders were offered surgery, that is, subsequent to a first series of
      radiation, a laryngectomy was performed (RT + S). For good responders (RT-I) or
      poor responders but medically unfit for and/or refusing surgery (RT-II), the
      radiation was continued after variable rest periods had elapsed (split-course
      radiation therapy). This paper analyzes 131 patients treated in the two
      institutions by this split-course regime protocol. Mean follow-up was 84 months;
      89% were male, 11% female. At 10 years a corrected survival of 55% and an overall
      survival of 20% was observed. For the RT-I the actuarial local relapse rate was
      56% versus a relapse rate of only 13% for the RT + S group. The corrected
      survival rates of the RT-I and RT + S were 54% and 70%, respectively. In
      contrast: 10 of 12 RT-II patients relapsed locally, and a corrected survival of
      only 21% was observed. The influence of overall treatment time (OTT) was studied
      by using the equation of the biological effective dose (BED), being defined as
      D(1 + d/alpha/beta) - (ln 2/alpha*Tp)*OTT). However, no clear relationship
      between BED and the risk for local and/or regional relapse could be established.

PMID- 8256769
TI  - Carboplatin (CBDCA) plus alpha interferon in metastatic non-small cell lung
      cancer. A Hoosier Oncology Group phase II trial.
AB  - Interferons have been shown to increase in vitro cytotoxicity of platinum
      compounds. The Hoosier Oncology Group has conducted a Phase II clinical trial to
      determine if interferon alpha-2a (IFN-alpha-2a) given in combination with
      carboplatin (CBDCA) can increase response rates or survival in patients with
      metastatic or recurrent inoperable non-small-cell lung cancer. Forty-four
      patients with no prior chemotherapy and high KPS (80-100) were enrolled. CBDCA
      400 mg/m2 was given intravenously on day 1 and IFN-alpha-2a 9 million units was
      given subcutaneously on days 1, 3, and 5. Treatment was administered every 4
      weeks until onset of progressive disease or to a maximum of 4 courses: 37
      patients (84%) received at least 2 courses, whereas only 16 (36%) received the
      full 4 courses. Dose-limiting toxicities were leukopenia (27%) and
      thrombocytopenia (20%) attributable to CBDCA. Grade 2-3 anemia occurred in 32%.
      Only 4-7% of patients experienced severe fever, fatigue, or flu-like symptoms
      attributable to interferon administration. Of 41 patients evaluable for response,
      there were no complete responses and only 3 (7.3%) partial remissions. The
      overall median survival was 6 months. The combination of CBDCA and IFN-alpha-2a
      given in this dose and schedule does not appear to have superior activity
      compared to CBDCA alone in patients with non-small-cell lung cancer.

PMID- 8256770
TI  - Second-line hormonotherapy for breast cancer. Uselessness of first-line
      continuation.
AB  - The hypothesis that the results of second line hormonotherapy for breast cancer
      may be ameliorated with continuation of the first line has been explored in a
      randomized trial. Patients progressing under tamoxifen were randomly allocated to
      aminoglutethimide and hydrocortisone acetate with or without tamoxifen
      continuation. No difference has been observed between the two arms in terms of
      response rate and progression-free overall survival.

PMID- 8256771
TI  - Multicenter phase II study of brequinar sodium in patients with advanced breast
      cancer.
AB  - In this study, 34 patients with advanced breast cancer were treated with
      brequinar sodium: 75% of the patients were postmenopausal, and 94% had received
      chemotherapy previously; 50% had previously received an anthracycline-containing
      regimen. Brequinar was administered intravenously at a median weekly dose of
      1,200 mg/m2. The toxicity was moderate, with 17 patients (50%) experiencing grade
      3 or 4 toxicity. There were 33 patients evaluable for response: 4 patients (12%;
      95% confidence interval, 3.4-28.2%) achieved partial responses, 10 patients (30%)
      were stable, and 19 patients (58%) had progressive disease. We conclude that, at
      this dose and schedule, brequinar has only modest activity in patients with
      advanced breast cancer.

PMID- 8256772
TI  - A Gynecologic Oncology Group phase II study of amonafide (NSC 308847) in
      epithelial ovarian cancer.
AB  - In this study, 19 evaluable patients with epithelial ovarian cancer were treated
      with amonafide 300 mg/m2 over an hour for 5 consecutive days every 3 weeks. One
      partial response (5%) was seen. Hematologic toxicity was substantial with grade 3
      or 4 toxicity occurring as follows: leukopenia, 10 patients (45%);
      thrombocytopenia, 6 patients (27%); granulocytopenia, 8 patients (36%). No other
      unusual or severe toxicity occurred. In view of the low response rate and high
      toxicity, amonafide does not warrant further investigation in epithelial ovarian
      cancer.

PMID- 8256773
TI  - Prospective: breast cancer adjuvant therapy after two decades. Clinical progress
      but a "partial circle" in investigation.

PMID- 8256774
TI  - Cisplatin and 5-fluorouracil as salvage therapy for recurrent metastatic squamous
      cell carcinoma of the anal canal.

PMID- 8256775
TI  - Use of the positive predictive value to correct for disease misclassification in
      epidemiologic studies.
AB  - Misclassification problems of the disease status often arise in large
      epidemiologic cohort studies in which the outcome is classified on the basis of
      record linkage with routinely collected error-prone data sources, such as cancer
      registries or mortality statistics. If the misclassification is nondifferential,
      i.e., independent of the exposure status, this leads to bias toward the null in
      estimates of relative risk. A variety of methods have been proposed to correct
      for this bias. Most approaches are based on estimates of the sensitivity and
      specificity of disease classification from validation studies, which typically
      require invasive and time-consuming diagnostic procedures. For ethical and
      practical reasons, such procedures may often not be applied on individuals
      classified as not having the disease, in which case estimates of sensitivity and
      specificity cannot be obtained. In this paper, an alternative correction method
      is proposed based on estimates of the positive predictive value, which requires
      validation of the diagnosis among samples of individuals classified as having the
      disease only. The method is applicable in situations with either differential or
      nondifferential specificity of disease classification as long as the sensitivity
      is nondifferential. Point estimates and large-sample interval estimates of the
      corrected relative risk are algebraically derived. The performance of the method
      is assessed by extensive simulations and found to be satisfactory even for small
      sample sizes.

PMID- 8256776
TI  - Has risk-factor epidemiology outlived its usefulness?

PMID- 8256777
TI  - Re: "Magnetic fields of video display terminals and spontaneous abortion".

PMID- 8256778
TI  - Re: "Pregnancy and lactation as determinants of bone mineral density in
      postmenopausal women".

PMID- 8256779
TI  - Bacterial pneumonia in adult populations with human immunodeficiency virus (HIV)
      infection.
AB  - Recurrent bacterial pneumonia was recently added to the definition of the
      acquired immunodeficiency syndrome (AIDS), based on the observation that
      bacterial pneumonia rates have been increased in human immunodeficiency virus
      (HIV)-infected persons and are indicative of immunosuppression in this
      population. Nonetheless, risk factors for bacterial pneumonia among HIV-infected
      persons remain largely uninvestigated. Identification of risk factors that may be
      associated with bacterial pneumonia can guide development of future interventions
      and further clarify target groups for such interventions. From a methodological
      viewpoint, diagnostic algorithms need to be further standardized to provide
      comparable estimates of disease incidence. Epidemiologic studies will also need
      to address the effectiveness of chemoprophylaxis and vaccine interventions in HIV
      infected populations. Since clinical trials will not be feasible for testing
      efficacy of interventions that are already recommended, observational data will
      be critically important in guiding clinical practice.

PMID- 8256780
TI  - Simulation study of confounder-selection strategies.
AB  - In the absence of prior knowledge about population relations, investigators
      frequently employ a strategy that uses the data to help them decide whether to
      adjust for a variable. The authors compared the performance of several such
      strategies for fitting multiplicative Poisson regression models to cohort data:
      1) the "change-in-estimate" strategy, in which a variable is controlled if the
      adjusted and unadjusted estimates differ by some important amount; 2) the
      "significance-test-of-the-covariate" strategy, in which a variable is controlled
      if its coefficient is significantly different from zero at some predetermined
      significance level; 3) the "significance-test-of-the-difference" strategy, which
      tests the difference between the adjusted and unadjusted exposure coefficients;
      4) the "equivalence-test-of-the-difference" strategy, which significance-tests
      the equivalence of the adjusted and unadjusted exposure coefficients; and 5) a
      hybrid strategy that takes a weighted average of adjusted and unadjusted
      estimates. Data were generated from 8,100 population structures at each of
      several sample sizes. The performance of the different strategies was evaluated
      by computing bias, mean squared error, and coverage rates of confidence
      intervals. At least one variation of each strategy that was examined performed
      acceptably. The change-in-estimate and equivalence-test-of-the-difference
      strategies performed best when the cut-point for deciding whether crude and
      adjusted estimates differed by an important amount was set to a low value (10%).
      The significance test strategies performed best when the alpha level was set to
      much higher than conventional levels (0.20).

PMID- 8256781
TI  - Risk factors for cancers of the nasal cavity and paranasal sinuses among white
      men in the United States.
AB  - A case-control analysis of cancer of the nasal cavity and sinuses was performed
      using data from the 1986 National Mortality Followback Survey. Data on cigarette
      smoking, alcohol consumption, usual diet, and other factors from 147 white men
      who died from nasal cancer and from 449 controls who died from other causes were
      compared. Cigarette smoking was related to an increased risk of nasal cancer,
      with a doubling of risk among heavy or long-term smokers and a reduction in risk
      among long-term quitters. Among nonsmokers, having a spouse who smoked was
      associated with a significantly elevated risk of nasal cancer. After adjustment
      for smoking, a significant dose-response relation was also noted between alcohol
      drinking and risk of nasal cancer. High consumption of salted/smoked foods was
      associated with elevated risk, and risk tended to decrease with increasing intake
      of vegetables. Associations were more pronounced for cigarette smoking and
      certain dietary items when the analysis was restricted to maxillary sinus cancer.
      The study confirms that cigarette smoking is a risk factor for nasal cancer, and
      provides further evidence that dietary factors may play a role in the etiology of
      this malignancy.

PMID- 8256782
TI  - Longitudinal study of blood pressure: changes and determinants from adolescence
      to middle age. The Dormont High School follow-up study, 1957-1963 to 1989-1990.
AB  - The changes and determinants of blood pressure were examined in the Dormont High
      School (Pittsburgh, Pennsylvania) cohort of 86 men and 116 women with mean ages
      of 17 years during high school (1957-1963), 34 years at follow-up I (1977-1978),
      and 47 years at current follow-up II (1989-1990). Over the 30-year period, the
      subjects' mean systolic blood pressure changed relatively little, whereas the
      increase in mean diastolic blood pressure was significantly higher in men than in
      women (p < 0.01). Based on the criteria of diastolic blood pressure > or = 90
      mmHg, and/or current use of antihypertensive medication, 18% developed
      hypertension. Compared with nonhypertensives, hypertensives had significantly
      higher baseline systolic blood pressure (p < 0.001); higher weight at all ages (p
      < 0.05); and gained more weight over the period (p < 0.01). By means of
      multivariate analyses, it was found that baseline systolic blood pressure,
      current weight, and weight gain were significantly and independently associated
      with current systolic blood pressure level and hypertension. These data indicate
      that initial systolic blood pressure level at adolescence, current weight, and
      weight gain are important determinants of risk of high blood pressure, and there
      is a further suggestion of sex and age differences in the critical period of
      risk.

PMID- 8256783
TI  - Incidence of insulin-dependent diabetes mellitus in young adults: experience of
      1,587,630 US Navy enlisted personnel.
AB  - First hospitalizations (n = 1,293) for diabetes mellitus between 1974 and 1988
      were used as a surrogate for insulin-dependent diabetes mellitus incidence among
      17-34-year-old US Navy enlisted personnel followed for 6,077,856 person-years. In
      the 15-year period, the overall incidence of insulin-dependent diabetes mellitus
      was 21.3 per 100,000 person-years. Incidence did not differ significantly by sex,
      but was higher for blacks than whites (28.4 vs. 20.2 per 100,000 person-years,
      respectively; p < 0.05). Incidence increased with age threefold for white men and
      fivefold for black men (p < 0.05) between the ages of 17-19 and 30-34 years.

PMID- 8256784
TI  - Immunologic response to oral cholera vaccination in a crossover study: a novel
      placebo effect.
AB  - The authors conducted a two-period crossover study of the reactogenicity and
      immunogenicity of live oral cholera vaccine CVD 103-HgR among US university
      students. Subjects ingested 5 x 10(8) colony forming units of either killed
      Escherichia coli K12 placebo or vaccine, followed by the opposite treatment one
      week later. Surprisingly, the dynamics of the immunologic response were
      influenced by prior ingestion of placebo. Subjects who received placebo first
      showed stronger vibriocidal antibody responses 2 weeks after vaccination compared
      with subjects who received vaccine first; this same pattern was seen for
      antitoxin titers. The authors suggest that ingestion of E. coli K12 one week
      prior to immunization boosts the immunologic response to vaccine by an unknown
      mechanism. Future crossover studies that examine immunologic outcomes might be
      designed to explore the ubiquity of such an effect.

PMID- 8256785
TI  - Estimation of design effects and diarrhea clustering within households and
      villages.
AB  - The degree to which diarrheal disease clustered within households and within
      villages among preschool age children was examined using data from four
      population-based prevalence surveys undertaken in Malawi, Zambia, Indonesia, and
      Nepal over the past decade. The design effect for each cluster survey was
      calculated using the diarrhea prevalence, the cluster sizes, and the magnitude of
      diarrhea clustering within the sampling unit (villages). A recently developed
      statistical method, alternating logistic regression, was used to estimate disease
      associations within households of up to nine preschool age children residing
      within villages of up to 589 such children. Pairwise odds ratios estimating
      diarrhea clustering within villages ranged from 1.03 (95% confidence interval
      (CI) 1.01-1.07) in Zambia to 2.19 (95% CI 1.73-2.78) in Indonesia. The design
      effects ranged from 2.07 (95% CI 1.26-3.19) in Zambia to 7.93 (95% CI 5.16-11.52)
      in Indonesia. Design effects were strongly dependent on cluster size. The design
      effects for clusters of size 50 would have ranged from 1.38 to 4.73. Pairwise
      odds ratios for diarrhea clustering within households ranged from 1.88 (95% CI
      1.61-2.19) in Nepal to 10.05 (95% CI 8.46-11.94) in Indonesia. Household odds
      ratios were always larger than village odds ratios. The village and household
      pairwise odds ratios adjusted for age, the type of latrine used by the household,
      and presence of a market in the village were slightly higher than the unadjusted
      odds ratios. Alternating logistic regression provided useful estimates of disease
      clustering within villages and household while allowing for covariate adjustment.

PMID- 8256786
TI  - Consensus Development Conference on Osteoporosis. Hong Kong, April 1-2, 1993.

PMID- 8256787
TI  - Biochemical markers of bone turnover. I: Theoretical considerations and clinical
      use in osteoporosis.
AB  - The recent development of noninvasive techniques to measure bone mass and bone
      turnover represents a major advance in the diagnosis and management of
      osteoporosis. The rate of formation or degradation of the bone matrix can be
      assessed either by measuring a prominent enzymatic activity of the bone-forming
      or resorbing cells, such as alkaline and acid phosphatase activity, or by
      measuring bone matrix components released into the circulation during formation
      or resorption. Recent studies have shown that the appropriate combination of the
      most efficient markers of bone resorption and formation will provide a powerful
      tool in the clinical investigation of osteoporosis.

PMID- 8256788
TI  - Biochemical markers of bone turnover. II: Diagnosis, prophylaxis, and treatment
      of osteoporosis.
AB  - Osteoporosis is a major health problem and is becoming increasingly important in
      our aging society. In many of the Western countries, patients with hip fracture
      occupy more hospital beds than patients with any other disease. Measures to
      combat osteoporosis are urgently needed, but the best way of doing so is
      uncertain. Osteoporosis prevention can be targeted at a subgroup of the
      population at high risk of disease. Alternatively, the intervention can be aimed
      at the entire population. Both preventive strategies have been proposed for
      osteoporotic fractures. Some researchers advocate population programs to increase
      weight-bearing exercise and calcium intake or to reduce smoking, but there is
      little direct evidence of their effectiveness. The most widespread opinion is
      that bone mass measurement is the most accurate predictor of fracture risk.
      Prediction of fracture risk may mean treatment for several years with drugs with
      not only effects, but also adverse effects. This encourages attempts to optimize
      the diagnostic procedures.

PMID- 8256789
TI  - Risk assessment: theoretical considerations.
AB  - Measurements of bone mass and several other skeletal characteristics can
      effectively identify women at high risk for fractures. These measurements are now
      widely available, and other clinical data cannot provide equivalent information.
      Treatments exist that will preserve bone mass and presumably reduce fracture risk
      (although for newer treatments this requires further study). It should also be
      noted that the prevention of very rapid bone loss may also protect against the
      development of micro-architectural abnormalities, thereby further reducing risk.
      Even in the very old, for whom preservation of bone mass may be of less value,
      there now appears to be an intervention that diminishes the impact trauma
      associated with falls. In this group bone mass measurements may also aid in
      identification of the highest risk groups. It is worth noting that measurement of
      bone mass may further serve to motivate patients to accept or to continue with a
      therapy.

PMID- 8256790
TI  - Osteoporosis in men: epidemiology, pathophysiology, and treatment possibilities.
AB  - The neglect of the problem of fractures in men may be the result of the focus on
      the enormity of the problem in women, attention to vertebral fractures and the
      role of menopause in the pathogenesis of fractures and cardiovascular disease,
      and the role of hormone replacement therapy in the prevention of fractures and
      cardiovascular disease. The use of epidemiology as a means of understanding the
      disease in individuals has confirmed that fractures are a common and serious
      consequence of osteoporosis in women--and in men.

PMID- 8256791
TI  - Bone mass, nutrition, and other lifestyle factors.
AB  - Since the proceedings of the last Consensus Conference on Osteoporosis were
      published as a supplement to The American Journal of Medicine in November 1991,
      there has been a plethora of well-documented studies reported in the literature.
      This article will address some of the issues concerning the relation between bone
      mass and nutrition raised in those studies.

PMID- 8256792
TI  - Bone mass and exercise.
AB  - The overall role of exercise as an integral part of osteoporosis prevention and
      treatment remains unclear and controversial. Comparatively well accepted are the
      facts that disuse results in bone mass loss, that sedentary individuals in
      general have less bone mass than exercising individuals (from cross-sectional
      study data), that exercise may produce a modest increase in bone mass (from
      longitudinal study data), and that exercise cannot compensate for estrogen loss.
      However, numerous questions regarding exercise and the skeleton remain to be
      answered, such as how the apparent osteogenic effect of exercise is mediated,
      what is the relationship of exercise in reducing fractures, how to reconcile the
      discrepancy between exercise-induced bone mass gain (lesser) and disuse bone loss
      (greater). At present, it seems reasonable to recommend avoidance of a sedentary
      existence, and participation in a moderate exercise program, for individuals
      seeking to prevent or treat osteoporosis, recognizing that much of the benefit
      may be in the resultant increase in muscle strength, in coordination, and in
      flexibility associated with such a program.

PMID- 8256793
TI  - Hormone replacement therapy for prevention and treatment of osteoporosis.
AB  - Estrogen therapy is clearly effective in the prevention and treatment of
      osteoporosis. Several estrogens and routes of administration are available. A
      progestin is required to protect the endometrium if the patient has a uterus. The
      duration of treatment required is unknown but probably is > or = 10 years for
      prevention and may be life-long, which is the requirement for patients with
      established disease. A regimen of patient monitoring can be easily established
      and must become routine for all patients on long-term treatment.

PMID- 8256794
TI  - Estrogen and estrogen-progestogen replacement: therapy and cardiovascular
      diseases.
AB  - The use of postmenopausal estrogens primarily to prevent heart disease should be
      reserved for women at high risk by virtue of an unfavorable low-density
      lipoprotein: high-density lipoprotein (LDL:HDL) ratio or the presence of manifest
      disease. Unopposed oral estrogen should improve lipoproteins within a few weeks,
      and this change, if sustained, should reduce the risk of cardiovascular disease.
      There is no reason to give progestins to a woman without a uterus. The management
      of a woman with an intact uterus is less well defined, given the unknowns about
      progestin's long-term effects on lipids or the heart.

PMID- 8256795
TI  - Calcitonin for prevention and treatment of osteoporosis.
AB  - There appears to be a consensus that 100 IU/day of nasally administered salmon
      calcitonin may prevent trabecular bone loss during the first year of the
      menopause. Strong evidence exists that half that dose may also be sufficient to
      prevent trabecular bone loss and that higher doses (> or = 200 IU/day) induce a
      significant increase in spinal bone mineral content. Calcium supplements should
      be systemically administered when calcitonin is given, particularly at high
      doses. Rectal calcitonin seems also to be an efficient alternative in prevention
      of trabecular bone loss. Further studies are required to evaluate the effect of
      calcitonin in prevention of cortical bone loss. In established osteoporosis
      calcitonin may prevent further bone loss at trabecular and cortical sites. A
      similar benefit is obtained following parenteral or nasal administration of the
      drug. Long-term administration of nasal salmon calcitonin induces a significant
      dose-dependent gain of bone at the lumbar spine, whereas discontinuous therapy
      with a ratio of 1:2 or 2:3 between the treatment and nontreatment periods is the
      best regimen for cortical bone. Epidemiological, retrospective, and prospective
      studies provide a convergent network of evidence that calcitonin administration
      in osteoporosis contributes to reduce significantly the frequency of subsequent
      fractures, both in the spine and in the hip. Finally, in established
      osteoporosis, nasal calcitonin possesses a potent analgesic effect, reduces the
      duration of bed confinement, and decreases the number of concomitant analgesic
      medications. The well-demonstrated effects of nasal calcitonin permit it to be
      considered as a highly rational solution for the prevention and the treatment of
      postmenopausal osteoporosis.

PMID- 8256796
TI  - The role of bisphosphonates in the prevention and treatment of osteoporosis.
AB  - Bisphosphonates are synthetic compounds that are taken up preferentially by the
      skeleton and suppress osteoclast-mediated bone resorption. There are structural
      differences among the various bisphosphonates that account for considerable
      differences in antiresorptive potencies and in activity/toxicity ratios.
      Bisphosphonates are given to patients with established vertebral osteoporosis,
      either intermittently or continuously, but controlled, long-term data are only
      available for intermittent regimens. They decrease the rate of bone loss,
      increase spinal bone mineral density (BMD), and stabilize BMD for at least 4
      years of treatment without any significant side effects. This increase in bone
      mass is not due to redistribution of calcium in the skeleton, as at sites with
      predominantly cortical bone, BMD values either do not change or increase with
      treatment. Bisphosphonates also appear to decrease the frequency of new vertebral
      fractures in some patients with established osteoporosis, but this effect needs
      to be verified. Other issues that need to be addressed include the optimal mode
      and dose of administration and hence the choice of bisphosphonate, the duration
      of treatment, the changes in bone metabolism following treatment arrest, and
      finally the efficacy of bisphosphonates in the prevention of hip fractures.

PMID- 8256797
TI  - Treatment of symptomatic osteoporosis with fluoride.
AB  - Fluoride has been used for > 30 years in the management of osteoporosis. It is
      one of the few agents that has marked anabolic effects on the skeleton. Indeed,
      treatment results in continued increments in cancellous bone volume so that
      cancellous bone volume can be restored to normal in patients with advanced
      osteoporosis. Despite its long history, both the efficacy and risks of fluoride
      regimens continue to be the subject of controversy. One of its problems is its
      age, and much of the early work undertaken utilized methodology and proofs that
      are today unacceptable. A further problem is that sodium fluoride as a treatment
      is cheap and not patented (although some formulations are), so that it has been
      difficult for investigators or industry to make the investments required to
      provide a modern program of evaluation.

PMID- 8256798
TI  - Bone mass measurement: prediction of risk.
AB  - Accurate assessment of individual fracture risk requires measurement of bone mass
      (density). Another strong risk factor for identifying women or men who will
      develop fractures in the near future is the presence of previous (spine and
      nonspine) fractures. However, the occurrence of a low-trauma fracture almost
      anywhere in the skeleton is indicative of a more advanced stage of disease and is
      associated with a substantial, further increase in fracture risk, independent of
      bone mass. Thus, prevention of the first fracture should receive priority. In a
      clinical setting, initial assessment of bone mass can be combined with other,
      known risk factors and projected over the patient's remaining life expectancy, to
      estimate future, cumulative fracture probability. Estimates such as "remaining
      lifetime fracture probability" can also approximate the impact and cost
      effectiveness of treatment, allowing for more objective and rational therapeutic
      planning for individual patients.

PMID- 8256799
TI  - Formation-stimulating regimens other than sodium fluoride.
AB  - Although no bone formation-stimulating regimen has been approved for treatment of
      established osteoporosis, there are a number of potentially effective drugs that
      are in various stages of preclinical and clinical testing. The two that show the
      greatest potential and the ones most likely to become available initially for
      clinical treatment are a parathyroid hormone fragment, PTH(1-34), and insulin
      like growth factor-I. A promising approach for the future is to discover orally
      active agents that enhance the local production of growth factors by bone cells.
      It is likely that effective formation-stimulating regimens will become available
      for treating established osteoporosis within the next 5 years.

PMID- 8256800
TI  - New treatment strategies: ipriflavone, strontium, vitamin D metabolites and
      analogs.
AB  - Drugs used to treat osteoporosis can be grouped in two main categories: those
      that decrease bone resorption and those that increase bone formation.
      Antiresorptive drugs are active in preventing bone fractures in patients
      characterized by a negative calcium balance. However, because antiresorptive
      agents are often coupled to inhibition of bone formation, inhibitors of bone
      resorption may not be candidates as potential curative drugs in osteoporosis.
      Conversely, drugs that act by increasing bone formation produce an increase in
      bone mass above the fracture threshold; therefore, these agents are good
      candidates for the treatment of osteoporosis. The ideal curative drug in
      osteoporosis should have the ability both to decrease bone resorption and to
      maintain a relatively high rate of bone formation, thus inducing a favorable
      uncoupling of bone remodeling.

PMID- 8256801
TI  - Prevention of hip fractures.
AB  - For a 50-year old Caucasian woman today, the risk of a hip fracture over her
      remaining life-time is about 17%. Tomorrow the situation will clearly be worse
      because the continuous increase in life expectancy will cause a three-fold
      increase in worldwide fracture incidence over the next 60 years. Through
      diagnostic bone mass measurements at the hip and assessment of biochemical
      parameters, a great deal has been learned in recent years about reduction of hip
      fracture risk. Preventive strategies are based on prevention of falls, use of hip
      protectors, and prevention of bone fragility. The latter includes the
      optimization of peak bone mass during childhood, postmenopausal estrogen
      replacement therapy, and also late prevention consisting in reversing senile
      secondary hyperparathyroidism, which plays an important role in the decrease of
      skeletal strength. This secondary hyperparathyroidism, which results from both
      vitamin D insufficiency and low calcium intake, is preventable with vitamin D3
      and calcium supplements. They have recently been shown capable of providing
      effective prevention of hip fractures in elderly women living in nursing homes,
      with a reduction of about 25% in the number of hip fractures noted in a 3-year
      controlled study in 3,270 women (intention-to-treat analysis). In conclusion, it
      is never too early to reduce the risk of osteoporosis and never too late to
      prevent hip fractures.

PMID- 8256802
TI  - Varadi syndrome (OFD VI) or Opitz trigonocephaly syndrome: overlapping
      manifestations in two cousins.
AB  - We report on 2 cousins, offspring of consanguineous matings, with multiple
      congenital anomalies. Square face, frontal bossing with metopic ridge, small
      anteverted nose, flat nasal bridge, slanted palpebral fissures, and epicanthal
      folds contributed to an unusual appearance. Multiple bucco-alveolar frenula and
      notched inferior alveolar ridges were present at birth and one had a notched
      uvula and submucous cleft of the hard palate. Both had congenital heart
      anomalies, micropenis, and cryptorchidism. Persistence of Mullerian structures
      was documented at necropsy in one patient. The surviving patient was mentally
      retarded and had unilateral central hexadactyly and partial agenesis of the
      corpus callosum. Bulimia and episodic hyperthermia were attributed to
      hypothalamic dysfunction. Results of unstimulated endocrine studies and
      gonadotropin releasing hormone (GnRH), and human chorionic gonadotropin (HCG)
      stimulation tests were normal. The manifestations of the 2 patients overlap those
      reported in the OFD VI and Opitz trigonocephaly syndromes.

PMID- 8256803
TI  - Is there a relationship between inborn errors of metabolism and extensive
      mongolian spots?
AB  - We report on a case of inborn errors of metabolism in association with extensive
      mongolian spots. We suggest that this association may be due to a disequilibrium
      of metabolism during embryonic development.

PMID- 8256804
TI  - Evaluation of families wherein a single male manifests a phenotype of X-linked
      lymphoproliferative disease (XLP).
AB  - The Epstein-Barr virus (EBV)-induced diseases of males with X-linked
      lymphoproliferative disease (XLP) include fatal infectious mononucleosis (IM),
      non-Hodgkin lymphoma (ML), agammaglobulinemia, and aplastic anemia. These
      phenotypes also occur as sporadic cases in families, and EBV seronegative males
      in these families must be considered at risk for XLP until they seroconvert
      normally to EBV. Given that 50% of males inheriting the defective XLP gene die
      following primary EBV infection, it is vital that they be identified pre-EBV
      infection. Here we report results using molecular genetic techniques to provide
      information as to the relative risks of EBV negative males and potential carrier
      females in ten families wherein a single male had died of IM.

PMID- 8256805
TI  - Congenital hypothyroidism presenting as apparent spondyloepiphyseal dysplasia.
AB  - An 11-year-old boy with short stature, dysplastic epiphyses, and vertebral
      abnormalities was thought to have spondyloepiphyseal dysplasia. He was
      subsequently found to have epiphyseal dysplasia secondary to congenital
      hypothyroidism. The radiographic findings in longstanding congenital
      hypothyroidism and spondyloepiphyseal dysplasia are compared and a possible
      mechanism for the dysplasia of hypothyroidism is discussed.

PMID- 8256806
TI  - The Williams syndrome: evidence for possible autosomal dominant inheritance.
AB  - We recently evaluated a mother and son with the Williams syndrome. Documentation
      of the clinical phenotype in two generations of this family suggests that some
      cases of the Williams syndrome are autosomal dominantly inherited. Recognition of
      the heritable nature of the Williams syndrome should prompt careful clinical
      evaluation of other at-risk relatives in order to provide accurate recurrence
      risk counseling.

PMID- 8256807
TI  - Metacarpophalangeal pattern profile analysis in Williams syndrome.
AB  - Many patients with Williams syndrome (WS) are not diagnosed until they are old
      enough to demonstrate the characteristic personality and facial changes. A number
      of these changes are quite subtle and none of them is present in all affected
      individuals. The cause of WS remains obscure and consequently, there are no
      cytogenetic, biochemical, or molecular studies to help in the diagnosis of
      patients in whom the diagnosis is uncertain. We have generated a mean WS
      metacarpophalangeal pattern profile (MCPP) on 21 clinically diagnosed individuals
      with WS. This mean syndrome profile shows that WS hands are smaller than average
      age-matched control hands and that the distal phalanx of the thumb is
      disproportionately large with respect to the rest of the hand. A mathematical
      model, which effectively discriminates WS patients from unaffected control
      individuals, was developed using discriminant analysis of the MCPP data. Of the
      21 WS patients classified by this method, only 2 were misclassified as "normal."
      Similarly, 2 of the 24 control individuals were misclassified as "WS," yielding
      an over-all successful classification rate of 91%.

PMID- 8256808
TI  - Williams-Beuren syndrome in monozygotic twins with variable expression.
AB  - Five sets of monozygotic (MZ) twins with Williams-Beuren syndrome (WBS) have been
      reported so far. We report on an additional pair of mz twins concordant for WBS
      but variable expression for the syndrome. Although both faces look different
      monozygosity of the twins was proven by DNA fingerprint analysis, HLA, and blood
      group pattern. Both girls had the typical facial appearance with strabismus. Both
      had developmental delay, mild supravalvular aortic stenosis (SVAS), hypoplasia of
      both pulmonary arteries and multiple peripheral pulmonary stenoses, and inguinal
      hernia. Unilateral renal agenesis was seen in one of the twins. In addition the
      pedigree pointed to a second disorder with probably autosomal dominant
      inheritance. Both twins had a cleft palate, but their father had cleft lip and
      the grandfather as well as the greatgrandfather had cleft lip/palate. Findings of
      linkage analysis in pedigrees with nonsyndromic oral facial cleft were taken to
      suggest that a major locus for nonsyndromal oral facial cleft is located on the
      distal portion of chromosome 6. Linkage studies could serve as a starting point
      to examine a locus associated with WBS. Our observation and reports on the
      literature support the hypothesis that WBS is a genetic disorder.

PMID- 8256809
TI  - Williams syndrome: autosomal dominant inheritance.
AB  - Williams syndrome (WS) usually occurs sporadically. Few familial cases of
      Williams syndrome have been described, and those reports have often lacked
      photographic documentation. We describe 3 families, including a 3-year-old boy
      and his 34-year-old father, a 2-year-old girl and her 30-year-old mother, and a 3
      year-old girl and her 31-year-old mother. None of these patients has
      supravalvular aortic stenosis or chromosome abnormalities. In all 3 families, the
      parent with Williams syndrome was diagnosed after the identification of the
      syndrome in the affected child.

PMID- 8256810
TI  - Inverted duplication of 8p: ten new patients and review of the literature.
AB  - We evaluated 10 patients with an inverted tandem duplication of 8p. Inverted
      duplications of chromosome 8 have been reported infrequently, and no syndrome has
      been previously identified. All 8 patients on whom birth histories were available
      were hypotonic at birth, and had feeding difficulties in the neonatal period. All
      patients have significant developmental delay. Manifestations present in 5 or
      more patients were prominent forehead, high arched palate, large mouth with a
      thin upper lip, malformed and/or apparently low-set ears, broad nasal bridge,
      dental and skeletal abnormalities, and joint laxity or hyperextensibility.
      Variation in the phenotype may, in part, be explained by the different
      breakpoints. Recurrence risks of de novo rearrangements are probably very low,
      but for the recombinants the risk may be significant. The duplication appeared to
      be de novo in 6 patients (both parental karyotypes were normal); maternal
      karyotypes were normal in 2 patients, and both parents of 1 patient were not
      available. One propositus had a monocentric recombinant of a paracentric inv(8)
      (p12p23.3) carried by the mother, and is one of only 6 known cases of duplication
      associated with a balanced paracentric inversion in a parent. The carrier parent
      was the mother in 5 of those 6 cases. Each case involved a different chromosome,
      and each probably was created by an unusual meiotic recombination event. Inverted
      duplication 8p is one of the most common duplications observed in our
      laboratories, and ranks in frequency with the classical deletions, such as Wolf
      Hirschhorn and cri-du-chat syndromes and duplication or secondary trisomy
      15q1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256811
TI  - Blepharophimosis sequence (BPES) and microcephaly in a girl with del(3)
      (q22.2q23): a putative gene responsible for microcephaly close to the BPES gene?
AB  - We report on a girl with the blepharophimosis sequence (BPES), microcephaly of
      postnatal onset, mild developmental retardation, and a deletion: 46,XX,del(3)
      (q22.2q23) de novo. A gene for BPES is suspected to be located at 3q23. Almost
      all cases with interstitial deletions containing 3q23 have not only BPES but also
      microcephaly and developmental retardation, while those without deletions,
      including those with apparently balanced translocations, only have BPES. Thus, a
      putative gene responsible for microcephaly may exist close to BPES gene. BPES,
      microcephaly, developmental retardation, and primary amenorrhea might constitute
      a contiguous gene syndrome.

PMID- 8256812
TI  - X-inactivation pattern in an Ullrich-Turner syndrome patient with a small ring X
      and normal intelligence.
AB  - In a description of 8 girls who had Ullrich-Turner syndrome (UTS) with a small
      r(X), mental retardation, and other unusual findings, it was hypothesized that
      the distinctive phenotype was associated with the loss of the X inactivation
      center from the r(X) and lack of genetic inactivation of the ring [Van Dyke et
      al., 1992]. Here, we present a 17-year-old young woman with
      45,X/46,X,r(X)(?p11q13) mosaicism, Ullrich-Turner syndrome, and normal
      intelligence. In situ hybridization with the X-centromere DNA probe DXZ1 (Oncor,
      Inc., Gaithersburg, MD) was performed on previously G-banded slides, and the
      probe hybridized to the centromere regions of the normal X and the ring. The r(X)
      appears to be inactivated since a buccal smear demonstrated 5% Barr bodies.
      Furthermore, DAPI stain and FISH analysis with the X-centromere DNA probe DXZ1
      was employed to distinguish the inactive X from the active X, and verified the
      presence of a sex chromatin mass in fibroblasts. These observations are
      consistent with the active-ring-X-and-mental-retardation hypothesis since the
      ring in this patient, although very small, appears to be normally inactivated and
      she has normal intelligence.

PMID- 8256813
TI  - Persistence of mullerian derivatives, lymphangiectasis, hepatic failure,
      postaxial polydactyly, renal and craniofacial anomalies.
AB  - We describe 3 unrelated newborn males with a previously unreported constellation
      of congenital anomalies. All 3 died neonatally of hepatic failure. Clinically,
      they presented with a pattern of malformations characterized by prenatal linear
      growth deficiency, hypertrophied alveolar ridges, redundant nuchal skin, and
      postaxial polydactyly. All 3 cases had male external genitalia with
      cryptorchidism, and 2 of them, a small penis. Necropsies showed similar internal
      anomalies, consisting of mullerian duct remnants, lymphangiectasis, and renal
      anomalies. The karyotypes were normal (46, XY) in skin fibroblasts (Case 1) and
      in peripheral blood lymphocytes (Case 3). Although this pattern of congenital
      anomalies must be differentiated from several other lethal syndromes, to our
      knowledge, no similar cases have been described previously. Cause of this
      syndrome is unknown. Because Case 2 had a previous brother with similar
      anomalies, we suspect that this new entity probably is an autosomal recessive or
      X-linked trait.

PMID- 8256814
TI  - Clinical, cytogenetic, and molecular evidence for an infant with Smith-Magenis
      syndrome born from a mother having a mosaic 17p11.2p12 deletion.
AB  - We describe an infant with del(17) (p11.2p12) whose deleted chromosome was
      inherited from a mosaic mother. The child had manifestations consistent with
      Smith-Magenis syndrome. The mother appeared to be of normal intelligence and she
      had minimal findings of Smith-Magenis syndrome. Separation of chromosome 17
      homologues in somatic cell hybrids and molecular studies confirmed the
      cytogenetic diagnoses and the fact that the mother was mosaic. Furthermore,
      molecular analysis demonstrated novel breakpoints in this family, with the
      deletion extending into and completely encompassing the markers duplicated in
      Charcot-Marie-Tooth (CMT) disease. Although this Smith-Magenis syndrome patient
      is completely deleted for the CMT region, her electrophysiological findings are
      different from those found in CMT. This is the only reported case of Smith
      Magenis syndrome with transmission from a partially affected mosaic mother.
      Transmission of interstitial deletions from mosaic parents may be more common
      than thought; therefore, parental chromosomes should be examined when
      interstitial deletions are identified.

PMID- 8256815
TI  - Natural history of the recombinant (8) syndrome.
AB  - The recombinant 8[Rec(8)] syndrome [rec(8), (8qter-->8q22.1::8p23.1-->8qter] is
      due to a parental inv(8)(8pter-->8p23.1::8q22.1-->8p23.1::8q22+ ++.1-->8qter).
      All inv(8) parents we have studied were of Hispanic origin. The Rec(8) phenotype
      consists of a characteristic set of minor facial anomalies, cardiovascular and
      other major malformations, and moderate to severe mental retardation. The
      clinical phenotype is relatively consistent in all published cases; however the
      natural history of the condition has remained unknown. Retrospective and
      prospective information on 42 propositi, spanning a period from 5 days to 23
      years, allowed us to define the natural history of this syndrome, tabulate the
      frequency and the evolution of phenotypic abnormalities, and share our experience
      with different therapeutic approaches.

PMID- 8256816
TI  - Schwartz-Jampel syndrome: an atypical form?
AB  - The Schwartz-Jampel syndrome (SJS) is an autosomal recessive disorder of
      myotonia, short stature, "mask-like" face, blepharophimosis, stiff joints, spinal
      malalignment, and pectus carinatum. The authors report on a 10-year-old girl with
      expressionless face, blepharophimosis, mild thoracic asymmetry, and myotonic
      electromyographic pattern, but without osteoarticular, spinal, and statural
      involvement. This appears to be one of the mildest form of SJS described so far.
      Contiguous genes could be an explanation for this and other atypical cases of
      SJS.

PMID- 8256817
TI  - Nonimmune hydrops fetalis in a 49,XXXXY fetus at 16 menstrual weeks.

PMID- 8256818
TI  - Mosaic r(13) in an infant with aprosencephaly.
AB  - We report on a stillborn male infant with a mosaic ring 13 karyotype (45,XY,
      13/46,XY,-13,+r(13)) with apparent aprosencephaly and clinical findings similar
      to those reported previously in the XK-aprosencephaly syndrome. Findings of
      patients with r(13) are often similar to those seen in individuals with del(13q).
      This case was unusual because of the presence of aprosencephaly, although brain
      malformations such as arhinencephaly and cerebellar hypoplasia are present in at
      least one-half of reported patients with 13q-. The overlap between these
      syndromes suggests a possible chromosomal model of the XK-aprosencephaly
      syndrome.

PMID- 8256819
TI  - DOOR syndrome (deafness, onycho-osteodystrophy, and mental retardation): a new
      patient and delineation of neurologic variability among recessive cases.
AB  - We report the seventeenth case of the recessive form of the DOOR syndrome. The
      parents were Guatemalan and not known to be consanguineous. The patient had
      developmental delay, severe sensorineural deafness, and abnormal nails and
      phalanges in the hands and feet. Urinary 2-oxoglutarate excretion was normal. The
      patient was among a subset of DOOR syndrome patients without seizures in infancy.
      This observation may be useful in discussing the prognosis for newly identified
      cases.

PMID- 8256820
TI  - Leukonychia totalis in two sibs.
AB  - A sister and a brother, offspring of unaffected consanguineous Arab parents, were
      found to have leukonychia totalis and flat, wide nails. To our knowledge this is
      the first report of apparent autosomal recessive transmission of this trait. A
      parental somatic mutation with gonadal mosaicism may explain the unusual
      segregation of the trait in this family.

PMID- 8256821
TI  - Cincinnati myocardial infarction and hormone family study: family resemblance for
      testosterone in random and MI families.
AB  - Familial correlations for total testosterone and free testosterone were examined
      in both random and nonrandom families participating in the Cincinnati Myocardial
      Infarction and Hormone Family Study (CIMIH). The non-random families were
      ascertained through Caucasian males who had survived a myocardial infarction (MI)
      prior to age 56 years, while random families were recruited largely through an
      adolescent boy maturation study. Eight sex-specific familial correlations were
      estimated (father-mother, father-son, father-daughter, mother-son, mother
      daughter, son-son, daughter-daughter, and son-daughter) for each of the MI and
      random samples using maximum likelihood methods with appropriate ascertainment
      correction. These familial correlations were examined for differences between the
      random and MI samples, as well as for sex-specific familial patterns. The results
      suggest that total testosterone levels may have a limited role in determining MI
      risk, as evidenced by the overall heterogeneity between samples, and lower serum
      levels in MI than random probands. The pattern of correlations for both androgens
      suggests that a simple genetic model appears unlikely; however, familiarity
      cannot be ruled out. Although possible covariate effects such as age and sex may
      have masked some potentially significant results, especially in males,
      familiarity in females is suggested (correlations ranging from .3-.9). The
      relative stability of these hormones in females as compared to that in males may
      have contributed to its identification, and suggests the familial
      transmissibility may be associated with adrenal production and/or metabolic
      clearance of testosterone.

PMID- 8256822
TI  - Malformations and minor anomalies in non-trisomic, autosomal aneuploidy.
AB  - We examined the medical records of 43 individuals with non-trisomic, autosomal
      aneuploidy evaluated by the Arkansas Genetics Program. Birthweight and the
      presence of malformations and minor anomalies by organ system were analyzed on
      each patient. Low birthweight was present in 28% (N = 12) of the patients, 72% (N
      = 31) of the subjects had a malformation, and 93% (N = 40) had a minor anomaly.
      Of the entire sample, the most common site of a malformation or minor anomaly was
      the limbs (79%). The most common site of a malformation was the head (21%), eyes
      (21%), or heart (26%). If a malformation was present, the head was significantly
      more likely (P < .04) than another body system to be the site of an additional
      malformation or minor anomaly. A malformation or minor anomaly of the ears was
      significantly more likely (P < .03) to be present when there was an associated
      eye anomaly than when no anomaly of the eye was identified. These data have
      implications for chromosome screening of individuals with malformations or minor
      anomalies and for the clinical evaluation of those found to have non-trisomic
      autosomal aneuploidy.

PMID- 8256823
TI  - Non-allelic heterogeneity of familial adenomatous polyposis.
AB  - Linkage studies on familial adenomatous polyposis (FAP) reported so far suggest
      that FAP is a genetically homogeneous disease. Recently, we found that the
      putative gene for Turcot syndrome, an apparently autosomal recessive clinical
      variant of FAP, is not allelic to FAP. Here we describe another family,
      segregating for an autosomal dominant disease clinically indistinguishable from
      FAP but genetically not linked to the APC locus, adding further evidence for the
      occurrence of non-allelic heterogeneity of FAP. These observations have
      implications to the linkage-based genetic counselling of persons at risk for FAP
      especially when they are drawn from small families giving insufficient
      information.

PMID- 8256824
TI  - Syndrome of tetraamelia with pulmonary hypoplasia.

PMID- 8256825
TI  - Cholesterol defect in Smith-Lemli-Opitz syndrome.

PMID- 8256826
TI  - Beyond the hospital walls.

PMID- 8256827
TI  - What you don't say can hurt you.

PMID- 8256828
TI  - This wasn't euthanasia.

PMID- 8256829
TI  - Case mismanagement.

PMID- 8256830
TI  - Nifedipine news.

PMID- 8256831
TI  - A four-step approach to pulmonary assessment.

PMID- 8256832
TI  - How to help confused patients.

PMID- 8256833
TI  - What color is that urine specimen?

PMID- 8256834
TI  - What patients really want from their nurses.

PMID- 8256835
TI  - CABG surgery: the second time around.

PMID- 8256836
TI  - Hip dislocation.

PMID- 8256837
TI  - New drugs. In the realm of the brain.

PMID- 8256838
TI  - Huntington's disease: helping the patient retain function.

PMID- 8256839
TI  - MedWatch: the new medical products reporting program.

PMID- 8256840
TI  - President picks Kristine Gebbie as the nation's first AIDS czar.

PMID- 8256841
TI  - With love always.

PMID- 8256842
TI  - Looking for angels.

PMID- 8256844
TI  - Selective ultraviolet radiation fractionation and polymerase chain reaction
      analysis of genetic alterations.

PMID- 8256843
TI  - The SCID mouse: relevance as an animal model system for studying human disease.
AB  - The simultaneous description some 5 years ago of two methods for the partial
      reconstitution of a human immune system in severe combined immune-deficient
      (SCID) mice (collectively, human:SCID mice) was met with great enthusiasm. At the
      time, it was hoped that human:SCID mice would provide experimental animal model
      systems for studying human disease and the human immune system. Many of these
      hopes have been borne out. Importantly, the experimental results obtained from
      these chimeric human/animal studies appear to be relevant to human disease and
      immune function. In spite of these glowing achievements, the SCID mouse may not
      represent the optimal experimental system with which to address these questions.
      The incomplete penetrance ("leakiness") of the scid mutation and the recent
      discovery that the mutation is not lymphoid specific, but rather affects a
      general DNA repair pathway, will only serve to complicate the interpretation of
      already complex biological interactions. Recently other immune-deficient mice
      have been described that appear to overcome one or both of these problems and
      thus these mice could represent improved hosts for the adaptive transfer of a
      human immune system. The current status of the SCID mouse in light of these new
      findings is discussed.

PMID- 8256845
TI  - In situ cDNA polymerase chain reaction. A novel technique for detecting mRNA
      expression.
AB  - We report a novel method for detecting intracellular messenger RNA by combining
      the techniques of in situ hybridization and polymerase chain reaction (PCR) (in
      situ cDNA PCR). The technique could detect low abundancy signals and distinguish
      different levels of gene expression. We examined the expression of the functional
      markers of activated cytotoxic T lymphocytes, granzyme A, and perforin in human
      lymphocytes from in vitro cultures. The amplification products were found in the
      cells and the supernatants, with the distribution critically affected by the
      protease digestion conditions. The specificity of amplification was confirmed by
      electrophoretic analysis and Southern blotting. We conclude that the in situ cDNA
      PCR technique offers a sensitive method of measuring the frequency of signal
      expressing cells and has significant research and clinical applications.

PMID- 8256846
TI  - Detection of anti-sense transcripts of the insulin-like growth factor-2 gene in
      Wilms' tumor.
AB  - The expression of the insulin-like growth factor-2 (IGF-2) gene was studied by
      means of both in situ hybridization and immunohistochemistry in eight cases of
      Wilms' tumor with different histological features. An anti-sense cRNA IGF-2 probe
      revealed the presence of abundant IGF-2 mRNAs in all eight tumors examined,
      localized in the most undifferentiated tumoral cells (blastemal cells); none of
      the tumors showed immunoreactivity for the anti-IGF-2 antibody. Using a sense
      cRNA IGF-2 probe, we also detected anti-sense transcripts of the IGF-2 gene in
      five of eight tumors. These transcripts were exclusively localized in the cells
      expressing the IGF-2 mRNAs. Although the function of these anti-sense transcripts
      is unknown, we think that their presence could explain the lack of IGF-2 peptides
      in Wilms' tumors despite increased expression of IGF-2 mRNAs.

PMID- 8256847
TI  - Expression of the apoptosis-suppressing protein bcl-2, in neuroblastoma is
      associated with unfavorable histology and N-myc amplification.
AB  - Survival rate in neuroblastoma, a tumor of post-ganglionic sympathetic
      neuroblasts, correlates with disease stage, tumor histology, and N-myc gene
      amplification. N-myc amplification is associated with rapid tumor progression and
      poor survival, but is not present in all cases of poor prognosis neuroblastoma.
      Moreover, overexpression of N-myc is not sufficient to cause cellular
      transformation. These data suggest that other genetic factors are important for
      neuroblastoma development. We investigated the expression of the, bcl-2 proto
      oncogene in untreated cases of neuroblastoma. bcl-2 is a novel proto-oncogene
      that promotes cell growth by inhibiting programmed cell death (apoptosis), a form
      of cellular demise common during normal neurogenesis. Immunocytochemical
      localization using a monoclonal anti-bcl-2 antibody revealed that 16 of 40
      patient specimens stained positive for bcl-2. bcl-2 was strongly associated with
      unfavorable histology (P = 0.002) and N-myc gene amplification (P = 0.002) and
      marginally associated with poor stage disease (P = 0.06). A logistic regression
      model evaluating the simultaneous association of stage, histology, and N-myc
      revealed that bcl-2 was most associated with unfavorable histology and N-myc gene
      amplification. These results support the notion that bcl-2 may play an important
      role in the genesis or progression of malignant neuroblastoma.

PMID- 8256849
TI  - Immunohistochemical detection of the NS4 antigen of hepatitis C virus and its
      relation to histopathology.
AB  - The immunohistochemical localization of the hepatitis C virus (HCV) nonstructural
      antigen 4 (NS4) was investigated in formalin-fixed human liver biopsy samples
      taken from 10 patients who were anti-HCV positive. NS4 was detected within the
      cytoplasm of hepatocytes in all HCV-positive patients studied, but not in the
      mononuclear cell infiltrates, bile duct epithelium, or endothelial cells. A high
      proportion of hepatocytes appeared positive, but the staining intensity was
      variable. After a coded histological evaluation of the liver tissue, the pattern
      of liver injury was shown to have no significant correlation with antigen
      positive hepatocytes, and no direct relationship was observed between the
      distribution of antigen-positive hepatocytes and areas of hepatocyte necrosis.
      The staining pattern was considered to be specific because liver samples from
      patients chronically infected with hepatitis B virus or from uninfected
      individuals were negative. Furthermore, no staining was noted when either
      preimmune rabbit serum or anti-NS4 adsorbed against the specific synthetic
      peptide was substituted for the primary antibody.

PMID- 8256848
TI  - Immunohistochemical localization of Trk receptor protein in pediatric small round
      blue cell tumors.
AB  - Expression of Trk protein has been documented by Northern analysis in
      neuroblastomas with good prognosis. To localize the expression of this protein at
      the cellular level within individual tumors, we adapted a recently characterized
      pan-Trk antibody for use in formalin fixed, paraffin-embedded tissue. We have
      examined a group of small round blue cell tumors occurring in children, including
      both high and low stage neuroblastomas, to assess the presence or absence of Trk
      expression and its cellular localization. Positive staining for Trk protein was
      observed in four of four low stage (good prognosis) neuroblastomas, five of five
      primitive neuroectodermal tumors/Ewing's sarcoma, five of five rhabdomyosarcomas,
      and no lymphomas. Within the neuroblastomas, expression of Trk protein was most
      striking in ganglion cells, in which positive cytoplasmic staining was
      demonstrated regardless of tumor stage. The latter observation may lend further
      insight into the pathobiology of this malignant childhood tumor.

PMID- 8256850
TI  - Somatostatin analogue (octreotide) inhibits bile duct epithelial cell
      proliferation and fibrosis after extrahepatic biliary obstruction.
AB  - Extrahepatic biliary obstruction leads to bile duct epithelial cell
      proliferation. Somatostatin and its analogue, octreotide, have been shown to
      inhibit DNA synthesis and proliferation in hepatocytes. We investigated the
      effect of octreotide on the biliary epithelial cell proliferative responses to
      biliary obstruction. Male Sprague-Dawley rats underwent common bile duct ligation
      and subcutaneous injection of either saline or octreotide (6 micrograms/kg) twice
      daily for 7 days. Morphometric analysis of hepatocytes, bile duct epithelial
      cells, and periportal connective tissue was performed by computerized point
      counting. Hepatocyte volume was preserved with octreotide treatment, which also
      significantly decreased bile duct proliferation and periportal extracellular
      matrix deposition in response to biliary obstruction compared with saline
      treated, duct-ligated animals. These results indicate that octreotide prevents
      the morphological changes that accompany extrahepatic biliary obstruction.

PMID- 8256851
TI  - Is the "preamyloid" of diffuse plaques in Alzheimer's disease really
      nonfibrillar?
AB  - Several papers have described an 'amorphous' component of the amyloid in diffuse
      plaques and it has been suggested that this is 'preamyloid,' which is not
      organized into fibrils. Because most of the studies have been performed on
      autopsy tissue it was the purpose of this study to compare the ultrastructure of
      diffuse amyloid deposits in well preserved Alzheimer's disease biopsy specimens
      with autopsy tissues from patients with Alzheimer's disease and Down's syndrome.
      A postembedding immunogold technique with anti-beta/A4 protein demonstrated gold
      particles exclusively on extracellular amyloid fibrils in both biopsy and autopsy
      brains. We have presented evidence that suggests the claim for the existence of
      an amorphous component within the beta/A4 protein-positive material is
      unconvincing.

PMID- 8256852
TI  - Acute side effects of homologous interleukin-3 in rhesus monkeys.
AB  - Interleukin-3 treatment of juvenile rhesus monkeys elicits a dose- and time
      dependent syndrome that includes urticaria, palpable lymph nodes, splenomegaly,
      thrombocytopenia, anemia, vomiting, diarrhea, intestinal bleeding, edema, and
      arthritis, apart from a strong stimulation of hemopoiesis. Arthritis was found to
      occur significantly more often in animals expressing the major histocompatibility
      complex alleles B9 and Dr5. Histological analysis revealed an abundance of mast
      cells in urticaria and, to a lesser extent, in lungs and synovia of arthritic
      joints. Active osteoclasts were abundant in ribs and arthritic joints.
      Extramedullary hemopoiesis was encountered in liver, spleen, and kidneys. The
      spleen showed deposits of hemosiderin, and in the liver, Kupffer cells were
      loaded with iron, indicating enhanced turnover of hemoglobin. Lymph nodes and
      bone marrow showed macrophages involved in hemophagocytosis, which probably
      contributed to the development of anemia and thrombopenia. Biochemical parameters
      in sera were indicative of parenchymal liver damage, with cholestasis and
      increased erythrocyte destruction. The side effects were strongly reduced in
      monkeys subjected to total body irradiation just before interleukin-3 treatment.
      Histamine antagonists were not significantly effective in preventing side
      effects, which is explained by the perpetual stimulation of basophilic
      granulocytes by exogenous interleukin-3. The nature of the side effects indicates
      that interleukin-3 may be involved in the pathogenesis of acute type
      hypersensitivity reactions and arthritis.

PMID- 8256853
TI  - Immunohistochemical localization of advanced glycosylation end products in
      coronary atheroma and cardiac tissue in diabetes mellitus.
AB  - Advanced glycosylation end products (AGEs) accumulate on long-lived extracellular
      matrix proteins and have been implicated in the micro- and macrovascular
      complications of diabetes mellitus. Within the arterial wall, AGE-modified
      proteins increase vascular permeability, inactivate nitric oxide activity, and
      induce the release of growth-promoting cytokines. Recently developed anti-AGE
      antibodies were used in an immunohistochemical analysis of coronary arteries
      obtained from type II diabetic and nondiabetic patients. High levels of AGE
      reactivity were observed within the atherosclerotic plaque present in vessels
      from selected patients with diabetes. Considered together with the pathological
      effects of AGEs on vascular wall homeostasis, these data support the role of
      advanced glycosylation in the rapidly progressive atherosclerosis associated with
      diabetes mellitus.

PMID- 8256854
TI  - Localization of mRNAs representing collagenase and TIMP in sections of healing
      human burn wounds.
AB  - Interstitial collagenase, a matrix metalloproteinase, is known to be actively
      involved in remodeling of cutaneous tissues including those affected by trauma,
      neoplasia, and inflammation. Conversely, collagenase activity is blocked by
      tissue inhibitor of metalloproteinases (TIMP). Because both collagenase and TIMP
      are rapidly secreted into the extracellular matrix, their sites of synthesis
      remain ambiguous. To determine the site and sequence of collagenase and TIMP
      expression in cutaneous wound repair, we examined partial and full thickness
      excisions of human burn wounds representing days 2 to 34 postinjury. Prominent
      labeling for collagenase and TIMP was detected in epithelial cells at the burn
      margin and at the edges of surviving hair follicles and eccrine sweat structures
      in the wound bed. Within the dermis, cells expressing collagenase and TIMP were
      at first perivascular in location and later appeared at the interface zone
      between viable and nonviable dermis. A diversity of cell types including
      macrophages, fibroblasts, endothelial cells, and keratinocytes appeared to
      express mRNAs for collagenase and TIMP. Little if any labeling was detected in
      necrotic regions, in adjacent nonwounded dermis, or epidermis. Our data indicate
      that collagenase and TIMP are temporally and spatially regulated during cutaneous
      wound repair.

PMID- 8256855
TI  - Differential expression of SKALP/Elafin in human epidermal tumors.
AB  - Recently we described a new epidermal serine proteinase inhibitor, skin-derived
      antileukoproteinase (SKALP), also known as elafin. SKALP/elafin was found to be
      absent in normal human epidermis, but can be induced in vitro and in vivo under
      hyperproliferative conditions. Here we studied the expression of SKALP/elafin in
      several types of epidermal tumors (basal cell carcinoma, squamous cell carcinoma,
      Bowen's disease, actinic keratosis, and keratoacanthoma). Using
      immunohistochemical staining SKALP/elafin appeared to be differentially expressed
      in these tumors. Functional measurements of anti-proteinase activity, and Western
      blotting of tumor extracts confirmed our findings at the histological level. In
      well differentiated squamous cell carcinoma, SKALP/elafin messenger RNA was
      demonstrated by non-radioactive in situ hybridization. We conclude that
      SKALP/elafin is a marker for abnormal or disturbed squamous differentiation. A
      possible role of SKALP/elafin in the control of tumor cell invasion is discussed.

PMID- 8256856
TI  - The human peripheral lymph node vascular addressin. An inducible endothelial
      antigen involved in lymphocyte homing.
AB  - The extravasation of blood-borne lymphocytes into organized lymphoid tissues and
      sites of chronic inflammation is directed in part by interactions of lymphocyte
      surface adhesion molecules, known as homing receptors, with tissue-selective
      endothelial ligands called vascular addressins. In mice and humans, lymphocyte L
      selectin and the peripheral lymph node addressin (PNAd) form a homing receptor
      endothelial ligand pair involved in lymphocyte traffic to peripheral lymph node
      (PLN). We have examined the tissue distribution and function of human PNAd, using
      monoclonal antibody MECA-79 and in vitro assays of L-selectin-dependent
      lymphocyte binding. We demonstrate that PNAd is expressed by human high
      endothelial venules (HEV) in lymphoid tissues which support lymphocyte adhesion
      via a PLN-associated recognition system. MECA-79 inhibits adhesion to these HEV
      of a cell line that binds predominantly via the PLN-homing receptor, L-selectin,
      but has no effect on adhesion by a mucosal HEV-binding cell line. Furthermore,
      MECA-79 blocks binding of human peripheral blood mononuclear cells to both PLN
      and tonsil HEV, but not significantly to HEV in the appendix. In addition, we
      demonstrate PNAd induction on venules at chronic inflammatory sites in humans,
      particularly sites with severe or long-standing chronic inflammatory involvement.
      These results confirm that PNAd functions as a PLN vascular addressin in humans,
      and that in addition to directing normal lymphocyte recirculation to lymph nodes
      and tonsils, this addressin likely participates in lymphocyte recruitment to
      sites of chronic inflammation.

PMID- 8256857
TI  - Survey of the distribution of a newly characterized receptor for advanced
      glycation end products in tissues.
AB  - Advanced glycation end products (AGEs), the final products of nonenzymatic
      glycation and oxidation of proteins, are found in the plasma and accumulate in
      the tissues during aging and at an accelerated rate in diabetes. A novel integral
      membrane protein, termed receptor for AGE (RAGE), forms a central part of the
      cell surface binding site for AGEs. Using monospecific, polyclonal antibody
      raised to human recombinant and bovine RAGE, immunostaining of bovine tissues
      showed RAGE in the vasculature, endothelium, and smooth muscle cells and in
      mononuclear cells in the tissues. Consistent with these data, RAGE antigen and
      mRNA were identified in cultured bovine endothelium, vascular smooth muscle, and
      monocyte-derived macrophages. RAGE antigen was also visualized in bovine cardiac
      myocytes as well as in cultures of neonatal rat cardiac myocytes and in neural
      tissue where motor neurons, peripheral nerves, and a population of cortical
      neurons were positive. In situ hybridization confirmed the presence of RAGE mRNA
      in the tissues, and studies with rat PC12 pheochromocytes indicated that they
      provide a neuronal-related cell culture model for examining RAGE expression.
      Pathological studies of human atherosclerotic plaques showed infiltration of RAGE
      expressing cells in the expanded intima. These results indicate that RAGE is
      present in multiple tissues and suggest the potential relevance of AGE-RAGE
      interactions for modulating properties of the vasculature as well as neural and
      cardiac function, prominent areas of involvement in diabetes and in the normal
      aging process.

PMID- 8256858
TI  - Protection from tumor necrosis factor-mediated cytolysis by platelets.
AB  - Infiltrating macrophages elicit tumor-destructive reactions by releasing
      cytolytic factors including tumor necrosis factor alpha (TNF-alpha). Because
      platelets represent another major component of the cell infiltrate in tumors, we
      examined whether they could affect TNF alpha-induced cell death. Exposure of L
      929 fibrosarcoma cells to human platelets reduced TNF alpha-induced cytotoxicity
      and cytolysis, as determined by 51Cr release assay and DNA fragmentation assay.
      This inhibitory effect, which depended on the concentration of platelets (0.1 to
      10 x 10(6)/0.1 ml), was as high as 50%. The decrease in responsiveness to TNF
      alpha reflected neither a degradation of TNF-alpha nor an inability of L-929
      cells to bind TNF-alpha. Indeed, even though Scatchard analysis indicated the
      presence of 100 to 150 125I-TNF-alpha binding sites/platelet with a kd of 3.8 to
      6.4 nM, addition of platelets up to 5 x 10(6)/0.1 ml did not compete with 125I
      TNF-alpha binding to L-929 cells. Furthermore, addition of platelets 1 or 2 hours
      after that of TNF-alpha was still protective suggesting that platelets rather
      promoted hyporesponsiveness of L-929 cells to a postbinding effect of TNF-alpha
      Platelet-induced reduction of TNF-alpha response could be reproduced with
      supernatant fluids from platelets incubated at 37 degrees C for 24 hours. The
      platelet-derived factor responsible for this effect was found to be a lipid of
      low molecular weight with high affinity for albumin and charcoal. A role for
      12(S) hydroxyeicosatetraenoic acid is proposed because this metabolite reduced
      TNF-alpha-induced cytolysis in a dose-dependent manner, whereas other platelet
      derived lipids including thromboxane A2 and platelet activating factor were
      inactive. These observations indicate that the role of associated platelets has
      to be considered when analyzing the cytotoxic and cytolytic activity of
      macrophage-derived TNF-alpha on tumor cells.

PMID- 8256859
TI  - Differential loss of E-cadherin expression in infiltrating ductal and lobular
      breast carcinomas.
AB  - The epithelial-specific cell-cell adhesion molecule E-cadherin was analyzed
      immunohistochemically on tissue sections of 89 human primary infiltrating breast
      carcinomas, using monoclonal antibodies 6F9 (for cryostat sections) and 5H9 (for
      cryostat and paraffin sections). The tumors included 41 well and moderately
      differentiated infiltrating ductal carcinomas (IDCs) most of which (78%) showed
      strong linear staining at the cell borders at a level, as high as luminal cells
      of normal mammary glands. The 26 poorly differentiated, more highly malignant
      IDCs examined also were all positive for E-cadherin, although a higher proportion
      of them (54%) showed reduced staining, which was heterogeneous and dotted over
      the cell borders. In contrast, 19 of 22 infiltrating lobular carcinomas (ILCs),
      which were either of the dispersed (classical), solid, or the mixed type, did not
      express E-cadherin, whereas three cases showed weak staining. In situ lesions of
      ILCs and pure lobular carcinoma in situ (four cases) were all E-cadherin
      negative, whereas intraductal carcinomas (11 cases) exhibited mostly strong
      staining. The results were confirmed by Western blotting. The data indicate that
      loss of E-cadherin expression is an early event in the formation of the lobular
      type of breast carcinomas. The absence of E-cadherin signifies a partial loss of
      epithelial differentiation and may account for the extended spread of lobular
      carcinoma in situ and the peculiar diffuse invasion mode of ILC. The generation
      of dedifferentiated IDCs can only in part be correlated with reduced expression
      of the intercellular adhesion molecule E-cadherin. Other factors are obviously
      also involved during invasion of this carcinoma type.

PMID- 8256860
TI  - Overexpression and abnormal modification of the stress proteins alpha B
      crystallin and HSP27 in Alexander disease.
AB  - Alexander disease is a leukodystrophy characterized by the presence of numerous
      Rosenthal fibers, inclusion bodies in astrocytes. A major component of Rosenthal
      fibers is alpha B-crystallin, some of which is ubiquitinated. In this report, we
      show that Alexander central nervous system (CNS) tissues contain elevated
      messenger RNA and protein levels of both alpha B-crystallin and the related small
      heat shock protein, hsp27, and that Rosenthal fibers contain hsp27. The alpha B
      crystallin and hsp27 polypeptide isoform patterns of Alexander disease CNS are
      also distinct from those of control samples, suggesting that postranslational
      modifications may be involved in Rosenthal fiber formation. We advance the
      hypothesis that Rosenthal fibers may be regarded as stress protein inclusions
      formed in astrocytes as part of a chronic stress response to an as yet unknown
      stimulus in the CNS of Alexander patients.

PMID- 8256861
TI  - Identification of carbohydrate structures in glycoprotein peptide maps by the use
      of LC/MS with selected ion extraction with special reference to tissue
      plasminogen activator and a glycosylation variant produced by site directed
      mutagenesis.
AB  - Electrospray ionization mass spectrometry utilizing a single quadrupole on line
      with reversed-phase HPLC (LC/MS) enables the characterization of glycoproteins in
      a relatively short period of time. In this approach the protein is digested with
      a suitable protease and the peptides are separated by reversed-phase HPLC and
      detected by electrospray ionization mass spectrometry. The glycopeptides are
      initially observed as a cluster of negatively sloping ions in a contour plot of
      data from the LC/MS run (m/z vs retention time) or as a characteristics series of
      masses at different elution times. The search for a particular glycopeptide is
      based on previously known carbohydrate structures and on consensus glycosylation
      sites. Further structural information is obtainable with glycosidase digestion
      and LC/MS analysis. The mass shifts following glycosidase digestion allow further
      confirmation of the structure. This approach identifies the site of attachment of
      two hybrid glycoforms to the T11 tryptic peptide in a reversed-phase tryptic map
      of recombinant tissue plasminogen activator (rt-PA). Use of selected ion
      extraction of the LC/MS data files allows one to graphically describe the elution
      order of closely related glycopeptides. The potential of LC/MS for the
      characterization of small amounts of unknown glycoproteins is shown by the study
      of an rt-PA mutant. A new potential site for glycosylation is created by site
      directed mutagenesis of wild type rt-PA with replacement of a threonine residue
      with asparagine at residue 103. An examination of a tryptic map shows that the
      mutant contains two new complex carbohydrate chains. The introduction of the new
      asparagine proximal to asparagine 117 changes this native high-mannose site in rt
      PA to a complex-type glycosylation. This method allows rapid identification of
      carbohydrate containing peptides and yields useful structural information on
      microgram amounts of material.

PMID- 8256862
TI  - Optimizing fluorescence detection in chemical separations for analyte bands
      traveling at different velocities.
AB  - In many separation techniques, such as field flow fractionation, liquid
      chromatography, and electrophoresis, chemical species form bands that migrate at
      distinct velocities. If these bands are to be quantified on-line using a shot
      noise-limited detection system, then attention must be given to the data
      digitization rate and to the removal rate of molecules from the analyte pool as a
      result of the detection process. A theory is developed for calculating the signal
      to-noise ratio under such conditions, and it is specialized to the case of
      fluorescence detection in capillary electrophoresis. Using standard detection
      procedures in which the data-digitization rate and excitation intensity remain
      constant for the duration of a separation, detection sensitivity can vary by more
      than a factor of five for bands that arrive at the detection zone between
      migration times tau fast and 10 tau fast, where tau fast is the time after the
      start of the separation that the fastest migrating band arrives at the detection
      zone. To compensate for different band velocities, both the data-digitization
      rate and the excitation intensity must be decreased as separation time (tau)
      increases by the factor tau fast/tau. Only when these corrections are made can
      uniform sensitivity with the highest possible signal-to-noise ratio be achieved
      for each peak. These predictions are experimentally tested and compare favorably
      to observations.

PMID- 8256863
TI  - Stabilization of reactive species within polystyrene divinylbenzene polymer
      networks.
AB  - The effect of cross-linking, surface area, and porous nature of modified
      polystyrene-divinylbenzene (STY-DVB) reagents has been investigated. The supports
      were prepared via two techniques and modified to contain various chemical
      functionalities. These reagents were used in an on-line reactor for automated
      derivatization of amines in HPLC. The reproducibility of the response vs the
      physical nature of the porous support and the chemical functionality was
      determined. The ability to stabilize highly reactive acylating reagents toward
      high concentrations of aqueous base was found to be a complex interaction of pore
      size distribution, percent cross-linking, surface area, and absolute loading of
      the analytical reagent on the porous support.

PMID- 8256864
TI  - Sensitive circular dichroism spectroscopy based on nonlinear degenerate four-wave
      mixing.
AB  - Degenerate four-wave mixing is demonstrated as an effective and sensitive laser
      analytical spectroscopic method for circular dichroism measurements. A forward
      scattering degenerate four-wave mixing optical setup is used to obtain simple
      optical alignment, highly efficient wave mixing, and very effective use of low
      laser power. This nonlinear laser-based circular dichroism method offers many
      advantages, including easy and efficient optical signal collection, use of very
      short analyte path lengths (e.g., 0.1 mm), and excellent detection sensitivity
      that is comparable or better than conventional laser-based or non-laser-based
      circular dichroism methods. Using an analyte path length of only 0.1 mm, and a
      probe volume of 98 pL, a circular dichroism mass detection limit of 0.68 pg or
      2.8 fmol is reported for (+)Co(en)3(3+).

PMID- 8256865
TI  - Identification of the facile gas-phase cleavage of the Asp-Pro and Asp-Xxx
      peptide bonds in matrix-assisted laser desorption time-of-flight mass
      spectrometry.
AB  - Abundant ions corresponding to the gas-phase cleavage of the Asp-Pro and Asp-Xxx
      bonds of peptides in the process of matrix-assisted laser desorption were
      observed using a time-of-flight mass spectrometer equipped with both linear and
      reflector mass analyzers. Peptides containing the N-terminal sequence, Asp-Pro
      ... from an endoproteinase Asp-N digest yielded one peak in the molecular ion
      region in the linear mode and two equally abundant peaks in the reflector mode
      TOF mass spectra. The lower molecular masses in the reflector mode mass spectra
      could be eliminated by removing the Asp residue or derivatizing its side-chain
      carboxyl group. The observed mass differences did not correspond to any amino
      acid; however, by lowering the potential of the reflector to correct for the
      energy loss the mass difference was determined to be 115 Da, i.e., Asp. The
      extent and rate of this decomposition was compared with that obtained using a
      four-sector tandem mass spectrometer in the MS/MS mode of operation without and
      with a collision gas at collision cell potentials of 3.0 and 9.86 kV. These data
      suggest the Asp-Pro peptide bond is more labile than other peptide bonds in the
      gas phase. Abundant metastable decomposition of internal Asp-Pro bonds was also
      observed in larger peptides and proteins. Based on these latter data, a mechanism
      for this gas-phase cleavage is proposed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256866
TI  - High-performance liquid chromatography of amino acids, peptides, and proteins.
      123. Dynamics of peptides in reversed-phase high-performance liquid
      chromatography.
AB  - The dynamics of several peptides in reversed-phase high-performance liquid
      chromatography (RP-HPLC) have been investigated on both n-octadecyl (C18) silica
      and n-butyl (C4) silica sorbents. In particular, the conformational
      interconversions and the relative rates of chromatographic relaxation of
      bombesin, glucagon, and beta-endorphin on both C18 and C4 n-alkylsilicas were
      monitored by examining changes in the experimental bandwidths of these peptides
      as a function of temperature and column residence time under linear gradient
      elution RP-HPLC conditions. The observed band-broadening trends were correlated
      with previously derived retention parameters and thermodynamic descriptors of the
      association process determined for bombesin, beta-endorphin, glucagon, and a
      control peptide, penta-L-phenylalanine. This study confirms that bandwidth
      measurements can be used as an integral experimental component to study the
      effect of the secondary structure of peptidic solutes on their RP-HPLC retention
      behavior. Further, the data demonstrate the utility of RP-HPLC as a tool to
      examine peptide conformational dynamics at hydrophobic surfaces. The relevance of
      these results to the general phenomenon of peptide-lipid interactions is
      discussed in terms of the associated evidence for lipid-induced changes in the
      conformation of these three bioactive peptides.

PMID- 8256867
TI  - Flow-through optical biosensor based on the permanent immobilization of an enzyme
      and transient retention of a reaction product.
AB  - A new sensor based on the twofold immobilization of a catalyst and a reaction
      product in an optical flow cell is proposed. The packing material of the flow
      cell consists of two physically distinct layers: an upper layer of controlled
      pore glass (CPG) onto which the enzyme is immobilized, and a lower layer of
      suitable exchanger where the product of the enzymatic reaction is temporarily
      retained. The performance of the biosensor was tested by immobilizing peroxidase
      on CPG and retaining the product of the reaction between hydrogen peroxide, 4
      aminophenazone, and an aniline derivative on a Sephadex resin. The sensor can be
      used to monitor hydrogen peroxide and any previous reaction which yields it
      (e.g., any reaction catalyzed by an oxidase). The biosensor was applied to the
      determination of hydrogen peroxide and glucose in serum. The features of the
      determinations (linear ranges between 10 and 200 ng/mL, and RSD values smaller
      than 2%), in addition to the great consistency of the results with those obtained
      in the clinical determination of glucose by an AACC method and analyte recoveries
      between 95 and 105% testify to the excellent performance of the sensor.

PMID- 8256868
TI  - Characterization of immobilized Escherichia coli alkaline phosphatase reactors in
      flow injection analysis.
AB  - The characterization of immobilized Escherichia coli alkaline phosphatase
      reactors used in flow injection analysis is reported for factors such as optimum
      pH, activity, ionic strength, product inhibition, and substrate specificity. The
      kinetics of the immobilized enzyme was studied, and mathematical descriptions
      were developed for the use of an immobilized enzyme packed-bed reactor to
      evaluate the kinetic parameters and the number of active sites on the immobilized
      enzyme. Suppression of phosphatase activity by orthophosphate was found to be
      significantly reduced, and the Michaelis-Menten constant increased when the
      enzyme was immobilized and packed in a reactor. Immobilized E. coli alkaline
      phosphatase exhibited similar activity at pH 8 in Tris-HCl, NaHCO3 and borate-HCl
      buffers but slightly lower activity in NH3H2O-NH4Ac buffer. The performance of
      the immobilized enzyme reactor was not affected by the presence of up to 10 M
      Mg(II), Ni(II), Cd(II), Co(II), Mn(II), Cu(II), or urea, 1 M Fe(II), or 0.1 M
      Fe(III) in the substrate stream. The chelating agent EDTA, however, gradually
      deactivated the immobilized enzyme. The periodic restoration of enzyme activity
      was achieved following the removal and addition of zinc ions. The immobilized E.
      coli alkaline phosphatase packed-bed reactor was used to measure the alkaline
      phosphatase available phosphorus content of a number of model organophosphorus
      compounds. p-Nitrophenyl phosphate showed a linear response in the range of 1.6 x
      10(-7)-1.6 x 10(-4) M. This study forms part of a larger program to develop
      enzymatic systems for water quality measurement.

PMID- 8256869
TI  - Characterization of the thiol/disulfide chemistry of neurohypophyseal peptide
      hormones by high-performance liquid chromatography.
AB  - Methodology is described for characterization of the kinetics and equilibria of
      thiol/disulfide interchange reactions of the disulfide bonds in the
      neurohypophyseal peptide hormones arginine vasopressin and oxytocin and the
      related peptides pressinoic acid and tocinoic acid. Thiol/disulfide interchange
      reaction mixtures are analyzed by reversed-phase high-performance liquid
      chromatography. The effect of mobile-phase composition and pH on the HPLC
      capacity factors for the native disulfide and reduced dithiol forms of each
      peptide was examined. In each case, the capacity factor decreases as the
      acetonitrile content of the mobile phase increases. For each disulfide/dithiol
      peptide pair, the capacity factor is larger for the dithiol form of the peptide,
      indicating that the hydrophobic side chains of the linear peptide are more
      accessible for interaction with the hydrophobic stationary phase. To illustrate
      application of the methodology, rate and equilibrium constants are reported for
      the thiol/disulfide interchange reactions of cysteine with arginine vasopressin
      at pH 7.0. Cysteine reacts with arginine vasopressin to form two mixed
      disulfides, which in turn react with another molecule of cysteine to give the
      dithiol form of arginine vasopressin and cystine. Rate and equilibrium constants
      were determined for each step by analysis of reaction mixtures by HPLC. The
      results are compared to rate and equilibrium constants for reaction of cysteine
      with oxidized glutathione.

PMID- 8256870
TI  - Chemical transformation/derivatization of O6-methyl- and O6-(hydroxyethyl)guanine
      for detection by GC-EC/MS.
AB  - In this project we set out to make an important class of DNA adducts, comprising
      O6-alkyl and O6-(hydroxyalkyl)guanines, susceptible to sensitive detection by GC
      EC/MS. While existing literature indicated that pentafluorobenzylation would be
      useful for the ring NH site on these compounds, how to best overcome the polarity
      of the exocyclic NH2 and OH groups, without losing the O6-alkyl moiety, was less
      clear. Working with O6-methylguanine and O6-(2'-hydroxyethyl)guanine as
      representative analytes, we found that the NH2 group could be converted into
      fluoro without loss of the O6 substituent. For the OH group, a comparison of
      several derivatives (OR') led to R' = tert-butyl as the best choice at this
      stage. The latter work, especially via NMR, also allowed exact structural
      assignments to be made for the N7 and N9 pentafluorobenzyl isomeric derivatives
      that formed. Of these R' derivatives, the N7 isomers migrated slower on silica
      TLC, had higher GC retention times, had lower responses by GC-EC/MS, and were
      preferentially destroyed as the GC column aged. However, the N9 isomer was slower
      on TLC when the OH was not derivatized. This behavior was rationalized using a
      concept of "polar footprint" for the derivatives. The concept also seemed to
      explain the puzzling GC-EC/MS behavior of some related compounds in our
      laboratory. Apparently the polar footprint should be minimized in designing
      derivatives for trace detection by GC-EC/MS.

PMID- 8256871
TI  - Fluorometric-enzymatic lactate determination based on enzyme cytochrome b2
      fluorescence.
AB  - This paper presents a procedure for fluorometric-enzymatic lactate determination
      based on the modification of the fluorometric properties of the enzyme L-lactic
      dehydrogenase (cytochrome b2). during the enzymatic oxidation of the analyte with
      ferricyanide. During the reaction one can observe an irreversible fall in the
      intensity of the enzyme's fluorescence, the rate of which is proportional to the
      concentration of the lactate. The source of this signal has been investigated and
      it has been shown that, besides the formation of a complex between the enzyme and
      the ferricyanide (the constant of which can be determined), this signal loss can
      be explained by simultaneous inner filter effects caused by the ferricyanide and
      the ferrocyanide (generated in the enzymatic reaction). A mathematical model has
      been developed which makes it possible to establish a linear response between the
      enzyme's analytical signal of fluorescence and the concentrations of the lactate,
      the cytochrome, and the ferricyanide. The procedure makes it possible to
      determine the lactate in concentrations ranging from 0.2 to 45 mg/L.
      Determination of the analyte has been carried out in milk samples with great
      precision and accuracy.

PMID- 8256872
TI  - Quantitative structure-retention and structure-odor intensity relationships for a
      diverse group of odor-active compounds.
AB  - Numerical representations of structure-based features are used to estimate both
      the retention indexes and sweetnesses of a diverse set of industrially important
      fragrance compounds. Retention indexes measured on nonpolar as well as polar
      stationary phases are modeled with accuracies of 3.6% and 5.6% at the mean of the
      respective retention ranges. Similar success was achieved when the developed
      equations were applied to predict the retention indexes of external data set
      compounds. Finally, the implications of using strictly 2-D structural information
      versus incorporating geometrical information are explored and discussed. The
      intensity of sweetness attributed to each compound is quantitatively predicted
      using identical multiple linear regression techniques. Difficulties encountered
      in this portion of the study warranted a critique of the procedures used to gain
      access to the odor data. As a consequence, the limited control exerted over
      several experimental variables is questioned.

PMID- 8256873
TI  - Changing ground rules for basic research.

PMID- 8256874
TI  - The science of prevention. A conceptual framework and some directions for a
      national research program.
AB  - A conceptual framework for studying the prevention of human dysfunction is
      offered. On the basis of recent advances in research on the development of
      psychological disorders and methods of preventive intervention, generalizations
      about the relation of risk and protective factors to disorder are put forward,
      along with a set of principles for what may be identified as the science of
      prevention. Emerging themes from the study of human development, in general, need
      to be incorporated in the models for explaining and preventing serious problems
      of human adaptation. The article concludes with a set of recommendations for a
      national prevention research agenda.

PMID- 8256875
TI  - Psychological interventions to prevent HIV infection are urgently needed. New
      priorities for behavioral research in the second decade of AIDS.
AB  - Behavior change remains the only means for primary prevention of HIV disease.
      Psychology should take a leading role in efforts to curtail the epidemic, but has
      not contributed to HIV prevention at a level proportionate to the urgency of the
      crisis. The authors propose an updated agenda for behavioral research on AIDS-HIV
      prevention implementing accelerated community trials of promising behavior change
      models, conducting trials of community-level interventions on a large scale and
      focused on populations most vulnerable to HIV infections, establishing
      partnerships between HIV research and community service organizations,
      integrating efforts from across psychology disciplines to advance and refine HIV
      prevention interventions, and mobilizing interdisciplinary HIV prevention
      resources and communication mechanisms to rapidly translate research findings to
      community and public policy arenas.

PMID- 8256877
TI  - Male violence against women. Current research and future directions.
AB  - This Psychology in the Public Forum section, authored by the American
      Psychological Association's Committee on Women in Psychology's Task Force on Male
      Violence Against Women and by Senator Joseph Biden, examines the prevalence,
      impact, and public policy dimensions of physical assault, sexual assault, and
      sexual harassment of women. This introduction reviews common themes that emerge
      from the articles that follow. It concludes by emphasizing that the problem of
      violence against women cannot be fully understood, let alone solved, by focusing
      exclusively on individual psychology. Only by changing the social and cultural
      institutions that have given rise to the problem can a lasting solution be
      achieved.

PMID- 8256876
TI  - Substance use and risky sexual behavior for exposure to HIV. Issues in
      methodology, interpretation, and prevention.
AB  - Recent reports have suggested that the use of alcohol or drugs is related to
      sexual behavior that is high risk for HIV infection. If substance use leads to
      unsafe sexual activity, understanding the dynamics of this relationship can
      contribute to research and preventive and educational efforts to contain the
      spread of AIDS. In this article, we review research on the relationship between
      substance use and high-risk sexual behavior. We then consider the inherent
      limitations of the research designs used to study this relationship, outline some
      methodological concerns including measurement and sampling issues, and comment on
      causal interpretations of correlational research findings. We end with a
      consideration of potential avenues for future research and a discussion of
      implications of these findings for current AIDS prevention policies.

PMID- 8256878
TI  - Violence against women. The congressional response.
AB  - America as a nation has for too long failed to grasp either the scope or the
      seriousness of violence against women. In this article, Senator Biden describes
      his attempt to address this issue through federal legislation. The Violence
      Against Women Act, first introduced in 1990 and reported favorably out of
      committee in May of 1993, takes aim at the problem from four different
      perspectives: rectifying imbalances, helping survivors, providing education, and
      requiring equal treatment. Each of these aspects of the legislation is discussed.

PMID- 8256879
TI  - Rape. Scope, impact, interventions, and public policy responses.
AB  - There are many ways for women to be victimized by strangers and by people they
      know, but rape is the crime women fear most. The research on the frequency,
      psychological aftereffects, somatic consequences, and immediate as well as
      delayed interventions for rape is reviewed; a brief consensus of the literature
      within each of these areas is developed; and the implications of the research for
      public policy are considered. Among the suggested policy responses are
      improvements in the databases on rape frequency, increased attention to
      measurement, a higher priority for teaching about rape in the education of health
      care providers, increased funding and technical assistance to rape crisis
      centers, and more diversity of interventions and research on their effects.

PMID- 8256880
TI  - Sexual harassment. Violence against women in the workplace.
AB  - Sexual harassment has been a fixture of the workplace since women first began to
      work outside the home. Although true epidemiological studies do not exist, large
      scale surveys of working women suggest that approximately 1 of every 2 women will
      be harassed at some point during their academic or working lives. The data
      indicate that harassment is degrading, frightening, and sometimes physically
      violent; frequently extends over a considerable period of time; and can result in
      profound job-related, psychological; and health-related consequences. This
      article provides a brief review of the prevalence and consequences of sexual
      harassment and outlines social policy implications for research, legislation, and
      primary prevention.

PMID- 8256881
TI  - Violence against women by male partners. Prevalence, outcomes, and policy
      implications.
AB  - Violence against women has only recently been addressed in national policy and
      legislation. Responses by most societal institutions to women assaulted by male
      partners are still based primarily on a lack of knowledge about the prevalence,
      severity, and outcomes of violence perpetrated by men against female intimates.
      Although well suited to make a vital contribution, psychologists still rarely
      involve themselves in proactive interventions with women victims. This article
      reviews empirical literature on the physical and sexual assault of women by their
      male intimates and discusses potential physical and psychological outcomes, with
      a focus on linking what is known about abused women's reactions with the rich
      literature on survivors' responses to trauma. Implications for research,
      treatment interventions, and policy are discussed.

PMID- 8256882
TI  - Mechanism of bronchospasm in aspirin-sensitive asthma.

PMID- 8256883
TI  - The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive
      asthmatics to aspirin.
AB  - A subset of persons with asthma develop bronchospasm, naso-ocular,
      gastrointestinal, and/or dermal reactions after ingesting aspirin (ASA) or agents
      with the capacity to inhibit cyclooxygenase. The bronchopulmonary reactions have
      been associated with a rise in urinary LTE4. We examined the effects of an
      inhibitor of 5-lipoxygenase, zileuton, in a group of eight asthmatic patients
      with known sensitivity to ASA accompanied by LTE4 hyperexcretion. We first
      confirmed ASA sensitivity and an increase in urinary LTE4 after ASA ingestion in
      these patients using a placebo-controlled ASA challenge. Subjects were then
      randomized to a double-blind, crossover trial to examine the effects of zileuton
      versus placebo on the response to ASA. Zileuton treatment decreased baseline
      urinary LTE4 excretion from a mean of 469 +/- 141 pg/mg creatinine to 137 +/- 69
      pg/mg creatinine (p < 0.02) and blunted the maximum increase in urinary LTE4
      after ingestion of ASA (3,539 +/- 826 pg/mg creatinine versus 1,120 +/- 316 pg/mg
      creatinine [p < 0.01]). The pre-ASA challenge FEV1 was unchanged by zileuton
      (3.41 +/- 0.15 L versus 3.35 +/- 0.17 L, zileuton versus placebo). Zileuton
      prevented the fall in FEV1 in response to ingestion of ASA; post-ASA ingestion
      the mean of the minimal FEV1 fell to 2.72 +/- 0.18 L on the placebo day while
      there was no significant fall on the zileuton day (3.26 +/- 0.17 L; p < 0.014).
      Zileuton also prevented the development of the nasal, gastrointestinal (p < 0.006
      and p < 0.025, respectively), and dermal symptoms which developed after ASA
      ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256884
TI  - Breathlessness during acute bronchoconstriction in asthma. Pathophysiologic
      mechanisms.
AB  - The purpose of this study was to examine potential contributing factors to
      breathlessness during bronchoconstriction, in particular, to evaluate the role of
      lung hyperinflation. We also wished to elucidate qualitative aspects of the
      unpleasant sensory experience and to identify factors that contribute to
      intersubject variability in subjective and objective assessments of airflow
      obstruction. We studied sensory-mechanical interrelationships during and after
      induced bronchoconstriction in 21 subjects with mild stable asthma.
      Breathlessness (Borg scale), spirometry, and inspiratory capacity (IC) were
      measured after each dose during methacholine bronchoprovocation to a maximal
      change (delta) in FEV1 of 50%. Breathing pattern, specific airway resistance
      (SRaw), plethysmographic thoracic gas volume, and maximal inspiratory mouth
      pressure (MIP) were recorded at baseline, at maximal response, and at full
      symptom recovery. End-expiratory lung volume (EELV) was derived from IC. Borg
      increased from 0.4 +/- 0.1 (very, very slight) at baseline to 5.0 +/- 0.5
      (severe) at maximal bronchoconstriction (mean +/- SEM, p < 0.001). FEV1 fell
      significantly (p < 0.001) to 48% predicted at maximal response. Of the 21
      subjects, 19 reported increased inspiratory rather than expiratory difficulty and
      predominantly described sensations of reduced inspiratory capacity and unrewarded
      inspiratory effort. Stepwise multiple regression analysis using delta Borg
      (outcome variable) versus changes in spirometry, SRaw, IC, and breathing pattern
      components, selected delta IC as the principal contributing factor: delta Borg =
      0.09 (delta IC, %fall); n = 193, r = 0.86, p < 0.001. delta IC continued to
      contribute significantly (p < 0.001) to the variance in Borg ratings after
      accounting for delta FEV1, and it was the strongest predictor of symptom recovery
      (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256885
TI  - Seasonal and allergenic predictors of bronchial responsiveness to distilled
      water.
AB  - To evaluate a possible seasonal change in bronchial responsiveness and the
      relation of such change to atopy, we administered 2,537 bronchial challenge tests
      in winter and spring to a dynamic population cohort of children 7 to 10 yr of
      age. The bronchial challenge test consisted of 10 min of tidal inhalation of an
      aerosol of ultrasonically nebulized distilled water; the resulting percentage
      decrease in FEV1 (dFEV1%) was recorded. Atopy was determined on the basis of skin
      test positivity (any wheal with a diameter greater than that obtained with a
      positive control) to seven allergens (cat dander, dog dander, house-dust mite,
      birch, raygrass, orchard grass, and Alternaria). Greater bronchial responsiveness
      in winter was independently and significantly predicted by a physician's
      diagnosis of asthma (difference in dFEV1%, 5.6; 95% confidence intervals [95%
      CI], 2.8 to 8.5; p = 0.0001) and by shortness of breath (difference in dFEV1%,
      4.2; 95% CI, 2.1 to 6.3; p = 0.0001). These factors were also predictive of
      greater responsiveness in the spring, as was atopy (difference in dFEV1%, 3.2;
      95% CI, 1.8 to 4.6; p = 0.0001). Analysis of specific allergens further revealed
      that reactivity to perennial allergens (house-dust mite, cat dander) was
      predictive of bronchial responsiveness in both winter and spring. However, the
      change in responsiveness between seasons was most significantly predicted by
      allergy to seasonal grass pollen, i.e., ragweed or orchard grass (change in
      dFEV1%, 2.6; 95% CI, 0.6 to 4.5; p = 0.01). In summary, our study demonstrates
      increased bronchial responsiveness in spring among children allergic to grass
      pollen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256886
TI  - Neutral endopeptidase activity and airway hyperresponsiveness to neurokinin A in
      asthmatic subjects in vivo.
AB  - In a previous study we have shown that inhibition of the endogenous neuropeptide
      degrading enzyme, neutral endopeptidase (NEP), potentiates airway narrowing to
      neurokinin A (NKA) in normal humans in vivo. In the present study, we tested the
      hypothesis that hyperresponsiveness to NKA in asthma is caused by a reduction in
      endogenous NEP activity. To that end, we used the NEP inhibitor, thiorphan, or
      placebo as inhaled pretreatment to NKA challenge in eight atopic asthmatic men,
      who were controlled by on-demand usage of beta 2-agonists alone. The dose of
      thiorphan pretreatment was obtained from pilot experiments in which 0.5 ml of a
      2.5-mg/ml concentration appeared to be the maximally effective nebulized dose.
      Dose-response curves to inhaled NKA (1 to 125 micrograms/ml, 0.5 ml/dose) were
      recorded on 2 randomized days 1 wk apart, in a cross-over study. To detect any
      effects of thiorphan on bronchoconstriction per se, we also investigated the
      effect of thiorphan or placebo on the dose-response curve to inhaled methacholine
      in a separate set of experiments. The response was measured by FEV1 and by
      partial expiratory flow-volume curves (V40p). The position of the dose-response
      curves was expressed as the concentration causing a 20% fall in FEV1 (PC20FEV1)
      or a 40% fall in V40p (PC40V40p). Baseline FEV1 and V40p were not affected by
      either pretreatment (p > 0.06). PC20FEV1 and PC40V40p to NKA were significantly
      lower after thiorphan pretreatment as compared with placebo (mean difference +/-
      SEM: 2.3 +/- 0.6 and 1.6 +/- 0.5 doubling dose, respectively; p <
      0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256887
TI  - Diet-induced thermogenesis in chronic obstructive pulmonary disease.
AB  - Increased resting energy expenditure and malnutrition are frequently observed in
      patients with COPD. The aim of this study was to examine the possible
      contribution of an increased diet-induced thermogenesis (DIT) to weight loss.
      Eleven patients with COPD in stable clinical state and 11 healthy control
      subjects were studied. Resting energy expenditure (REE) was measured by standard
      methods of indirect calorimetry, using a ventilated canopy. Premeal REE was
      measured after an overnight fast. All subjects then received a balanced liquid
      test meal with a caloric content that was 0.3 times their REE extrapolated to 24
      h. Diet-induced thermogenesis was measured over 130 min. Premeal REE was 109.9 +/
      11.7% of predicted values in the COPD group and 97.5 +/- 9.6% of predicted in
      the control group (p < 0.01). Seventy minutes after the test meal, REE had
      increased by 18.8 +/- 8.5% in the COPD group and by 15.1 +/- 5.8% in the control
      group (NS). After 130 min, REE had increased by 16.4 +/- 7.1% in the COPD group
      and by 12.4 +/- 5.3% in the control group (NS). The DIT expressed as a percentage
      of the caloric content of the meal was 4.3 +/- 1.6% in the COPD group and 3.3 +/-
      1.4% in the control group (NS). We conclude that patients with stable COPD,
      although hypermetabolic at rest, do not show an increased DIT.

PMID- 8256888
TI  - Large lungs after childhood asthma. A case-control study.
AB  - Several studies have suggested that the TLC after childhood asthma is increased
      compared wtih that in healthy subjects. The aim of this study was to assess
      whether TLC is increased after childhood asthma and whether this is associated
      with an increased growth of the lung during adolescence. During a mean period of
      29 months we studied 53 patients and 106 healthy control subjects who were
      matched for sex, age, and standing height. The patients had had asthma for a mean
      period of 10 yr. We found that in asthmatics TLC was increased in both sexes by
      about 7% predicted compared with that in the matched control subjects. The growth
      of TLC in ml/yr during adolescence was less in patients; this can be accounted
      for by a delay in pubertal development. When corrected for the delay in growth of
      stature, growth of TLC in ml/cm in asthmatics was similar to that found in
      control subjects. These findings support the hypothesis of a developmental change
      of enhanced lung growth during childhood asthma; they do not support a mechanism
      with progressive loss of elastic recoil of the lung.

PMID- 8256889
TI  - Risk factors for the persistence of respiratory symptoms in childhood asthma.
AB  - We studied the prognosis of childhood asthma in a cohort of 406 children 8 to 12
      yr of age when enrolled. Subjects were followed for a mean of 14.8 yr after their
      initial evaluation, with a follow-up rate of 86%. The mean age at follow-up was
      24.7 yr. We assessed the predictive value of sex and various childhood variables
      on the outcome of symptoms and medication use in adulthood. Although only 19% of
      subjects were still under a physician's supervision at the time of follow-up, 76%
      had respiratory symptoms, 32% used maintenance medication, and 22% used
      medication intermittently. The incidence of cigarette smoking was disturbingly
      high (33%). In adulthood, women were more likely than men to have symptoms (85
      versus 72%, respectively). The childhood symptom severity and the childhood
      degree of bronchial responsiveness in combination with a low %FEV1 were also
      related to the outcome of asthma in adulthood. The high prevalence of symptoms in
      adults at follow-up coupled with the low rate of physician supervision and
      medication usage suggest that more aggressive treatment may be indicated in
      asthmatic children.

PMID- 8256890
TI  - Comparison of nitrogen washout and plethysmographic measurements of lung volume
      in healthy infants.
AB  - Functional residual capacity (FRC), the only lung volume to be assessed routinely
      in infants, can be measured using plethysmography or gas dilution. Although it is
      well recognized that both methods yield similar FRC values in healthy adults, gas
      dilution techniques have consistently produced lower values in healthy infants
      when compared with plethysmography. However, interpretation of this difference is
      difficult since data comparing the different techniques within the same infants
      have rarely been reported. We performed paired measurements of FRC using an
      automated open-circuit nitrogen washout technique (FRCN2) and whole-body
      plethysmography (FRCpleth) in 11 healthy infants with a median age of 12 months
      (range, 2 to 18 months). The mean (SD) FRC was 21.7 (4.0) ml/kg for the N2
      washout and 25.6 (4.9) ml/kg for plethysmography. The mean within-subject
      difference between FRCN2 and FRCpleth was 3.9 (range, -0.3 to 7.2) ml/kg (p =
      0.001). Both N2 washout and plethysmography yielded reproducible results, with
      the mean of the coefficients of variation (CV) being 3.6 and 3.9%, respectively.
      The results from these paired measurements support previously reported data from
      separate populations of infants which suggest that gas dilution techniques
      consistently yield smaller values for FRC than do those measured by
      plethysmography.

PMID- 8256891
TI  - Pulmonary function growth velocity in children 6 to 18 years of age.
AB  - Pulmonary function growth rate varies with a child's stage of growth. Since
      attained pulmonary function reflects the cumulative effects of growth, insults,
      and repair, rate of growth may be a more sensitive indicator of a child's current
      pulmonary health status. The sample for analyses included 2,478 white boys and
      2,785 white girls followed annually by questionnaire and spirometry. Empirically
      derived annual growth velocities, peak velocity (Vpk), and age at which peak
      velocity occurred (Agepk) were determined for height, FVC, FEV1, and FEF25-75 for
      each child. Mean velocity curves for height, FVC, FEV1, and FEF25-75, stratified
      by sex and Agepk of height (an indicator for early, middle, or late maturity)
      were produced as a function of age. The differences between Agepk of FVC, FEV1,
      and FEF25-75 and Agepk of height (i.e., the lag period) were compared by sex and
      by the indicator of maturity. Linear regression analyses were performed to
      investigate associations between Vpk and Agepk of height, as well as between the
      lag period and Agepk of height. As is generally observed in height growth, there
      were considerable variations in the age of onset and magnitudes of the adolescent
      growth spurts of the pulmonary function parameters both between sexes and among
      children of the same sex. The duration of adolescent growth spurt appeared to be
      similar for all children, regardless of early, middle, or late maturity. Thus,
      those who matured earlier had shorter total growth periods than those who matured
      later. On the other hand, early maturers had greater growth velocities during
      preadolescence and greater adolescent Vpk than later maturers.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8256892
TI  - Reversible pulmonary responses to formaldehyde. A study of clinical anatomy
      students.
AB  - Epidemiologic studies of irritants are difficult to perform using standard
      epidemiologic methods for several reasons, including the reversible nature of the
      health outcomes, the selection of sensitive individuals from the study
      population, and the wide heterogeneity in normal responses to irritants. This
      study examined the feasibility of using repeated measurements of peak expiratory
      flow (PEF) and reported symptoms to study respiratory irritants and their effects
      in students exposed to formaldehyde during a clinical anatomy laboratory course.
      We studied 24 physical therapy students dissecting cadavers for 3 h per week over
      a 10-wk period. Formaldehyde exposures in the breathing zone ranged from 0.49 to
      0.93 ppm (geometric mean +/- geometric SD, 0.73 +/- 1.22). Irritant symptoms
      increased strongly over the course of the average laboratory period, but this
      effect was stronger at the beginning than at the end of the semester. PEF
      measured before each laboratory session declined over the semester by an average
      of about 10 L/min (2% of baseline), a trend that was statistically significant in
      random-effects regression models. After 14 wk away from the laboratory, the
      group's mean baseline PEF had returned to its preexposure level. Mean PEF also
      declined over each laboratory period, although this effect was attenuated over
      the course of the semester. Other important predictors of cross-laboratory PEF
      decrements were asthma and reporting throat irritation during the laboratory. It
      appears that mild irritant effects can be detected in naive subjects using a
      repeated monitoring design and relatively simple instrumentation.

PMID- 8256893
TI  - Association of indoor and outdoor particulate level with chronic respiratory
      illness.
AB  - The effect of indoor and outdoor particulate level on respiratory health was
      examined in 1,576 never smokers, 40 to 69 yr of age residing in industrial,
      residential, and suburban areas. The health outcomes of interest in this report
      were physician-diagnosed bronchitis, asthma, and six respiratory symptoms
      including chronic cough, chronic phlegm, bouts of cough and phlegm, shortness of
      breath (SOB), wheeze, and wheeze with SOB. Households with coal stoves had
      substantially higher indoor particulate levels than those with gas stoves.
      Subjects were grouped into three exposure categories according to the indoor use
      of coal stoves for both cooking and heating (B), either cooking or heating (E),
      or neither (N). The adjusted odds ratios for chronic phlegm, bouts of cough and
      phlegm, wheeze, and wheeze with SOB were significantly higher in the B than in
      the N group; the odds ratios for chronic cough and SOB were also higher for B
      than N, although these were not significant. The odds ratios in the E group were
      significantly greater for wheeze with SOB than in the N group but not for the
      other symptoms. The global estimates of the odds ratios for the six symptoms were
      1.4 and 2.0, respectively, for the E and B groups. The particulate level was
      highest in the industrial area and lowest in the suburban area. There was an
      excess risk of all respiratory symptoms among subjects residing in industrial and
      residential areas, with an increase in symptom prevalence with outdoor
      particulate levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256895
TI  - Tuberculosis control policies in major metropolitan health departments in the
      United States. V. Standard of practice in 1992.
AB  - Since 1978, we have surveyed the 28 metropolitan health departments initially
      reporting > 250 cases of tuberculosis/yr to determine the standard of practice in
      the control of pulmonary tuberculosis and the factors affecting treatment policy.
      In this survey, results were compared with data obtained in 1978, 1980, 1984, and
      1988. As in the previous years, all departments completed the survey. The
      predominant treatment regimen was 6 months of chemotherapy (64 +/- 1.33% of
      patients) involving isoniazid (I), rifampin (R), and pyrazinamide (Z). Estimated
      duration of treatment, which had decreased from 20.2 +/- 2.1 months in 1980 to
      7.58 +/- 1.02 months in 1988, increased to 9.34 +/- 2.32 months in 1992 (p <
      0.01). This was attributed to an increase in drug-resistant cases (17 of 25
      programs) and to increased incidence of HIV infection during the previous 4 yr.
      In 1984, HIV infection was estimated to coincide with tuberculosis in 2.54% of
      all patients, 7.72% in 1988, and 17.42% in 1992. Several other major departures
      from prior perceived practices were reported. In 1980, 32.1% of all patients were
      hospitalized initially for tuberculosis treatment, and this number decreased
      progressively to 17.8% in 1988; in 1992, 34.2 +/- 1.32% of patients with
      tuberculosis were hospitalized for initial treatment. In 1988, no program
      reported regular use of alternative therapy to isoniazid for chemoprophylaxis; in
      1992, 21 programs used alternative regimens (predominantly R-containing). In
      1992, nine programs reported increased funds for treatment of tuberculosis (27.2
      +/- 1.97% after inflation), whereas 16 reported a mean decrease of 14% after
      inflation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256894
TI  - Respiratory illness in persons with human immunodeficiency virus infection. The
      Pulmonary Complications of HIV Infection Study Group.
AB  - Although the pulmonary complications of advanced human immunodeficiency virus
      (HIV) infection have been well described, there is little information on
      respiratory manifestations of earlier disease. This report describes the
      respiratory disorders diagnosed over an 18-month period in a cohort of persons
      with or at risk for HIV infection with variable immunologic status. Cohort
      members were followed routinely and evaluated for respiratory disease by standard
      diagnostic algorithms. The 18-month incidence of each respiratory diagnosis was
      determined, and for frequent diagnoses, incidence by transmission category,
      location of residence, smoking status, CD4 count, and performance score at entry
      were compared. The most frequent respiratory diagnoses in HIV-seropositive cohort
      members were common to the general population: upper respiratory infection
      (33.4%), acute bronchitis (16.0%), acute sinusitis (5.3%), and bacterial
      pneumonia (4.8%). Pneumocystis carinii pneumonia occurred in 3.9%. Ambulatory
      respiratory illnesses were reported frequently regardless of immunologic status.
      The rates of P. carinii pneumonia and bacterial pneumonia were significantly
      greater in cohort members with entry CD4 counts < 250. Bacterial pneumonia
      occurred more frequently in injecting drug users and in cohort members with entry
      Karnofsky scores < 90. Disease stage and demographic and exposure factors are
      important variables affecting the respiratory manifestations of HIV infection.

PMID- 8256896
TI  - Two-step tuberculin testing in staff and residents of a nursing home.
AB  - This study examined the prevalence and determinants of tuberculin reactors and
      the booster response in 272 (97%) residents and 218 (69%) staff of an urban
      nursing home where a case of miliary TB was being investigated. Many subjects
      were foreign born (56%), and 15% had a history of BCG vaccination (34% of staff).
      Testing was done with 5 TU PPD-S (Connaught). Those with < 10 mm induration at 48
      h were retested at 1 wk. Test sizes > 9 mm were classified positive (reactors). A
      questionnaire was given to collect information on risk factors for a positive
      test. Results showed that 28% (36% staff and 22% of residents) of subjects were
      reactors at the initial test, 6% at the booster test (staff and residents), and
      32% at either test (40% staff and 26% residents). BCG (OR 4.8) and foreign birth
      (OR 1.7) were significantly associated with total reactors. The association with
      foreign birth was inversely related to the time since immigration. Only BCG was
      associated with a positive booster test (OR 6.7). Of positive tuberculin
      reactions in individuals with a history of BCG, 72% were attributed to the
      vaccine. We concluded that (1) staff as well as residents should be two-step
      tested when retesting is anticipated; (2) the prevalence of tuberculin reactors
      is highly related to the prevalence of BCG vaccinees and foreign birth; and (3)
      chemoprophylaxis is probably not indicated for isolated tuberculin reactors with
      a history of BCG.

PMID- 8256897
TI  - Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of
      tuberculosis in mice.
AB  - To identify alternative regimens for preventive therapy of tuberculosis, the
      pharmacokinetics and antimicrobial activities of rifampin (RMP), rifabutin (RBT),
      and rifapentine (RPT) were compared in BCG-vaccinated and M. tuberculosis
      infected immunocompetent mice. RPT showed the highest serum peak level (Cmax) and
      the longest half-life (t1/2), whereas RBT displayed the lowest Cmax and the
      shortest t1/2. On weight-to-weight basis, both RPT and RBT were more bactericidal
      than RMP. The activity of RMP was significantly reduced when the frequency of
      administration was reduced from six to three times weekly, whereas significant
      bactericidal activity was still observed in mice treated with RPT, 10 mg/kg up to
      once fortnightly, or RBT, 10 mg/kg twice weekly. Because the bactericidal
      activity of RBT, 10 mg/kg six times/wk for 6 wk, or RPT, 10 mg/kg two times/wk
      for 12 wk, was comparable to that of RMP, 10 mg/kg six times/wk for 12 wk in
      mice, the two regimens are appropriate for clinical trials of preventive therapy
      of tuberculosis.

PMID- 8256899
TI  - Quantitative cultures of endotracheal aspirates for the diagnosis of ventilator
      associated pneumonia.
AB  - Bronchoalveolar lavage (BAL) and protected specimen brushing (PSB) are the most
      commonly used methods for diagnosing ventilator-associated (VA) pneumonia
      although they require bronchoscopy. Endotracheal aspiration (EA) is a simple and
      less costly technique than PSB or BAL. The purpose of our study was to
      investigate the diagnostic value of EA quantitative cultures and to compare the
      results obtained using EA with those obtained using PSB and BAL in mechanically
      ventilated patients with or without pneumonia. We prospectively studied 102
      intubated patients divided into three diagnostic categories: Group I (definite
      pneumonia, n = 26), Group II (uncertain status, n = 48), and Group III (control
      group, n = 28). All patients received prior antibiotic treatment. EA, PSB, and
      BAL were obtained sequentially in all patients. When comparing Group I with Group
      III and using 10(5) cfu/ml as a threshold, we found that EA quantitative cultures
      represented a relatively sensitive (70%) and relatively specific (72%) method to
      diagnose VA pneumonia. The specificity of BAL and PSB (87% and 93%, respectively)
      was better than that of EA. The negative predictive value of EA cultures was
      higher (72%) when compared with that obtained using PSB (34%) (p < 0.05). EA
      quantitative cultures correlated with PSB and BAL quantitative cultures in
      patients with definite pneumonia. Although EA quantitative cultures are less
      specific than PSB and BAL for diagnosing VA pneumonia, our results suggest that
      the former approach may be used to treat these patients when bronchoscopic
      procedures are not available.

PMID- 8256898
TI  - Early bactericidal and sterilizing activities of ciprofloxacin in pulmonary
      tuberculosis.
AB  - The early bactericidal and sterilizing activities of ciprofloxacin were evaluated
      in the treatment of adult patients with smear positive pulmonary tuberculosis.
      Two randomized prospective studies were performed in Northern Tanzania. In study
      1, ten patients received either 750 mg ciprofloxacin or 300 ng isoniazid daily
      for 7 days. Counts of colony-forming units (cfu) of Mycobacterium tuberculosis in
      early morning sputum were performed. In study 2, twenty patients received either
      a standard regimen of rifampin (R), isoniazid (H), pyrazinamide (Z), and
      ethambutol (E) (regimen HRZE) or a trial regimen of ciprofloxacin (C), isoniazid
      (H), and rifampin (R) (regimen HRC). Sputum colony counts were performed for 8
      wk. Patients were tested for antibodies to human immunodeficiency virus (HIV)-1.
      The results demonstrate that ciprofloxacin alone has useful early bactericidal
      activity, resulting in a mean daily fall of 0.20 log10cfu/ml/day during 7 days
      compared with 0.25 log10cfu/ml/day for isoniazid. When HRZE and HRC regimens were
      compared, the HRC regimen appeared to be inferior in its sterilizing ability,
      with a culture conversion rate of 67% at 2 months compared with 100% for HRZE.
      The difference in outcome was most marked in HIV-1 positive patients. The role of
      ciprofloxacin in combination regimens may be as a bactericidal rather than a
      sterilizing agent.

PMID- 8256900
TI  - Serum type III procollagen peptide in patients with Pneumocystis carinii
      infection. The Copenhagen-Amsterdam PCP-Prednisolone Study Group.
AB  - Inflammation may play a central role in the pathogenesis of HIV-related
      Pneumocystis carinii pneumonia (PCP). Serum levels of the amino-terminal
      propeptide of Type III procollagen (PIIINP) reflect inflammatory activity in
      granulation tissue and in chronic rheumatic and liver disorders. To investigate
      changes in PIIINP serum levels during an episode of HIV-related PCP, consecutive
      serum samples were taken from 48 HIV-infected patients with PCP in a randomized,
      placebo-controlled study of the effect of adjunctive methylprednisolone therapy
      (26 in corticosteroid [CS] group and 22 in control group). All patients were
      treated with co-trimoxazole. In the control group, PIIINP serum levels at day of
      initiation of therapy (Day 0) were significantly higher in patients requiring
      mechanical ventilation and/or dying during the course of the pneumonia, and serum
      levels of PIIINP higher than 5 ng/ml were associated with a higher mortality than
      levels below 5 ng/ml. The level of PIIINP increased from Day 0 to Day 5. There
      was a significant correlation between changes in PIIINP levels and changes in the
      alveolar-arterial oxygen gradient from Day 0 to Day 5. In the CS group, the
      PIIINP levels decreased while steroid was administered. At Days 21 to 28 there
      were no difference in the levels of PIIINP between the two groups. PIIINP serum
      levels may predict the clinical outcome of PCP. The antimicrobial therapy may
      exacerbate the inflammatory reaction in HIV-related PCP, leading to respiratory
      failure. CS prevents this increased inflammatory activity.

PMID- 8256901
TI  - Upper and middle lobe bronchoalveolar lavage to diagnose Pneumocystis carinii
      pneumonia.
AB  - Pneumocystis carinii pneumonia (PCP) remains the most common lethal opportunistic
      pulmonary infection in patients infected with the human immunodeficiency virus
      (HIV). Although the use of prophylactic inhaled pentamidine has effectively
      reduced the frequency of primary and recurrent episodes of PCP, the
      aerosolization of pentamidine may have altered the localization of active PCP,
      resulting in more upper lobe disease. The distribution of disease may have also
      affected the diagnostic accuracy of standard bronchoalveolar lavage of the middle
      lobe, with a reduction in sensitivity from about 90 to 65%. In retrospective
      surveys of patients from our institution, Steiger and Fahy found that pooled
      multiple-lobe radiographic site-directed bronchoalveolar lavage resulted in
      diagnostic sensitivities of 91 and 100%, respectively. We performed a follow-up
      prospective study of 38 consecutive patients on aerosolized pentamidine in whom
      we lavaged both the middle lobe and an upper lobe. We found that bilobar lavage
      including routine lavage of an upper lobe increases the diagnostic sensitivity of
      bronchoalveolar lavage alone to 95% compared with 65% if lavage is performed only
      in the middle lobe (p < 0.05). Radiographic studies demonstrate a concordant
      increase in exclusive or predominant upper lobe disease in patients on
      aerosolized pentamidine, but our results indicate that PCP is recovered more
      frequently from the upper lobe regardless of the radiographic appearance. We
      conclude that all patients on prophylactic inhaled pentamidine should undergo
      bilobar lavage with the inclusion of an upper lobe in the initial evaluation of
      possible PCP. The diagnostic sensitivity of 95% makes bilobar bronchoalveolar
      lavage an acceptable sole initial diagnostic modality without the need for
      initial transbronchial lung biopsy.

PMID- 8256902
TI  - Metered-dose inhaler versus nebulized albuterol in mechanically ventilated
      patients.
AB  - In nonintubated patients, beta 2-agonist bronchodilators are equally effective
      when delivered by metered-dose inhalers (MDI) or nebulizers (NEB). The delivery
      of these drugs by MDI to intubated, mechanically ventilated patients has become a
      widespread practice. To compare the efficacy of the two delivery systems and
      establish optimal dosing, we prospectively randomized 10 mechanically ventilated
      patients, with increased airways resistance, to receive albuterol by either MDI
      or nebulizer in incrementally higher doses. After a 4-hr washout, patients were
      crossed-over to receive the drug by the alternative route of administration.
      Albuterol delivered by NEB to a total dose of 2.5 mg reduced the inspiratory flow
      resistive pressure (peak-pause airway pressures) from 21.5 +/- 5.7 to 17.6 +/-
      5.4 cm H2O (p < 0.01). Nebulized albuterol at cumulative doses of 7.5 mg led to
      further reductions in 8 of 10 patients (p < 0.1), but led to toxic side effects
      in 4 of them; in the remaining 6 patients toxicity occurred at a cumulative dose
      of 15.0 mg. By contrast, albuterol in cumulative doses reaching 100 puffs (9 mg)
      from an MDI administered into an endotracheal tube adapter did not significantly
      reduce resistive pressures, and produced no toxicity. We conclude that nebulized
      albuterol provides objective physiologic improvement, while albuterol
      administered by MDI through an endotracheal tube adapter has no effect in
      mechanically ventilated patients with airflow obstruction. Nebulizer treatments
      can and should be titrated to higher-than-conventional doses, using toxic side
      effects and physiologic response to guide therapy.

PMID- 8256903
TI  - Diaphragmatic fatigue after exercise in healthy human subjects.
AB  - The purpose of this study was to determine whether diaphragmatic fatigue occurs
      after high-intensity constant-load whole-body exercise to volitional exhaustion.
      Ten sedentary subjects with a maximal oxygen uptake of 2.52 +/- 0.47 L/min were
      studied. Subjects exercised on a bicycle ergometer at 80% of their maximal
      working capacity until volitional exhaustion. Minute ventilation during the last
      minute of exercise was 89.9 +/- 13.6 L/min, which represented 50 +/- 6% of the
      subjects' 12-s maximal voluntary ventilation. During the last minute of exercise,
      mean inspiratory esophageal pressure was 18.1 +/- 5.3 cm H2O, which represented
      only 15 +/- 4% of the subjects' maximal static inspiratory pressure. Bilateral
      transcutaneous supramaximal phrenic nerve stimulation was performed before and
      10, 30, 45 and 60 min after exercise. Twitch diaphragmatic pressure (twitch Pdi)
      was significantly decreased after exercise in seven of the 10 subjects. For the
      group as a whole, twitch Pdi fell from 28.9 +/- 3.7 cm H2O during control to 23.9
      +/- 5.1 cm H2O at 10 min after exercise (p < 0.005). The fall in twitch Pdi was
      due to a significant decrease in twitch esophageal pressure from 19.6 +/- 4.3 cm
      H2O during control to 15.5 +/- 4.9 cm H2O (p < 0.001). Twitch gastric pressure
      was not significantly different: 8.7 +/- 4.0 cm H2O, compared with 9.2 +/- 3.8 cm
      H2O during control. Twitch Pdi recovered to 93 +/- 7% of control values at 60 min
      after exercise. The fall in twitch Pdi after exercise indicates that
      diaphragmatic fatigue can occur following heavy endurance exercise in sedentary
      healthy persons.

PMID- 8256904
TI  - Effects of treatment on airway dynamics and respiratory muscle strength in
      Parkinson's disease.
AB  - To investigate how treatment can affect airway dynamics and respiratory muscle
      strength in Parkinson's disease (PD), we assessed maximum effort inspiratory and
      expiratory mouth pressures (MIP and MEP), oscillatory impedance, and maximum
      expiratory and inspiratory flow-volume curves (MEFV and MIFV) in 10 patients (8
      male and 2 female; mean age 51 +/- 5.3 yr, SD) after temporary interruption of
      antiparkinsonian therapy (off) and during continuous subcutaneous infusion of a
      direct stimulant of dopamine receptors, apomorphine (on). Treatment improved
      neurologic scores (off 25 +/- 5, on 9 +/- 5, modified Webster scale, p < 0.001),
      MEP (off 45 +/- 25, on 63 +/- 29 cm H2O, p = 0.003), and peak inspiratory flow
      (PIF; off 3.83 +/- 1.6, on 4.37 +/- 1.7 L/s, p = 0.028). Maximum inspiratory
      pressure was very low off treatment (-25 +/- 16 cm H2O) and improved moderately
      with apomorphine (-33 +/- 17 cm H2O) (p = 0.064). Total respiratory resistance
      during tidal breathing was normal in 9 patients both off and on treatment
      despite, in some cases, dramatic changes in MEFV and MIFV curves. These results
      suggest that abnormalities of the flow-volume curves may be due to problems in
      the rapid activation and coordination of contraction of upper airways and chest
      wall muscles during forced maneuvers, which is improved by apomorphine treatment.

PMID- 8256905
TI  - Corticosteroid withdrawal restores responses to calcium chelators and enhances
      cholinergic responsiveness.
AB  - To investigate the importance of the inflammatory response in acute peripheral
      airway constriction, we measured peripheral airway responses to calcium chelators
      and acetylcholine in anesthetized Basenji-Greyhound (BG) dogs before, during, and
      after chronic corticosteroid treatment. A wedged bronchoscope technique was used
      to measure peripheral airway resistance before and after aerosol challenge with
      4% Na2EDTA or acetylcholine (10 micrograms/ml) in contralateral lungs. After the
      initial measurements, five BG dogs received long-term treatment with
      methylprednisolone (2 mg/kg/d, subcutaneously), and five dogs were not treated
      and served as controls. Four weeks of methylprednisolone treatment almost totally
      abolished responses to Na2EDTA, but responses to acetylcholine did not change
      significantly. After discontinuing corticosteroid therapy, responses to Na2EDTA
      returned to levels found before corticosteroid treatment; responses to
      acetylcholine were significantly enhanced. We conclude that chronic
      corticosteroid treatment reduces acute response to calcium chelators and that
      withdrawal of corticosteroid therapy is associated with enhanced cholinergic
      responsiveness.

PMID- 8256906
TI  - Effects of aging on respiratory load compensation and dyspnea sensation.
AB  - To clarify effects of aging on the load compensation response and the sensation
      of dyspnea, we examined 28 healthy male volunteers for ventilatory and P0.1
      responses to hyperoxic progressive hypercapnia with and without inspiratory flow
      resistive loading (17 cm H2O/L/s) while the intensity of dyspnea was
      simultaneously assessed by visual analogue scaling every 15 s. Of the 28
      subjects, 14 were 61 to 79 yr of age and were classified as the older group; the
      others, 19 to 48 yr of age, were classified as the control group. Neither delta
      VE/delta PETCO2 nor delta P0.1/delta PETCO2 was different between the two groups
      without loading. In the control group, the delta P0.1/delta PETCO2 increased with
      loading (p < 0.01) without a change in the delta VE/delta PETCO2. In the older
      group, the delta P0.1/delta PETCO2 did not change with loading so that the delta
      VE/delta PETCO2 decreased with loading (p < 0.01). In the 28 subjects as a whole,
      the percent change in delta P0.1/delta PETCO2 with loading was inversely
      correlated with age (r = -0.53, p < 0.01). At PETCO2 levels of 45, 50, and 55 mm
      Hg, irrespective of loading, the dyspnea intensity was greater in the older group
      than in the control group, whereas the P0.1 expressed as its ratio to the
      predicted maximal inspiratory mouth pressure was not different between the two
      groups. We conclude that aging attenuates the compensatory response to
      inspiratory flow-resistive loading and it increases the intensity of dyspnea for
      a given level of PETCO2.

PMID- 8256907
TI  - Assessment of hypoxemia in patients with sleep disorders using saturation
      impairment time.
AB  - A method of recording cumulative nocturnal oxygen desaturation was utilized to
      develop a quantitative index of nocturnal hypoxemia (SIT index) to provide
      reference values and distributional properties for apneic and nonapneic sleep
      disordered patients. The SIT indices were compared in patients with varying
      degrees of obstructive sleep apnea (OSA) as determined by traditional methods of
      counting apneas and hypopneas. We studied 298 patients who were divided into five
      groups based on the presence and frequency of apnea or sleep-related respiratory
      deterioration. SIT indices for patient groups and individual patients were
      compared with the respiratory disturbance index (apneas + hypopneas x 60/total
      sleep time = RDI) using scatter plots, Kruskal-Wallis analysis of variance, and
      Mann-Whitney U tests. The OSA and non-respiratory-impaired patient groups had
      mean SIT values that were significantly different (p < 0.05). Subjects with
      severe apnea differed (p < 0.05) from subjects with mild and moderate apnea at
      SIT index thresholds < baseline, < 90, < 80, and < 70% SaO2, but subjects with
      mild and moderate apnea did not differ statistically from each other at any
      threshold. In individual patients with similar RDI values, considerable variation
      in SIT index can be seen, and the reverse is also true. This suggests that using
      both RDI and SIT may provide complementary information in assessing the severity
      of OSA.

PMID- 8256908
TI  - Transcutaneous and end-tidal carbon dioxide pressures should be measured during
      pediatric polysomnography.
AB  - Pediatric obstructive sleep apnea (OSAS) is characterized by partial airway
      obstruction, alveolar hypoventilation, and elevated arterial CO2 (PaCO2). Thus, a
      reliable, practical method of estimating CO2 is needed for pediatric
      polysomnography. Therefore, we measured both transcutaneous CO2 (PtcCO2) and end
      tidal CO2 (PETCO2) in 15 pediatric polysomnographic evaluations. Sleep state, the
      highest PtcCO2, and the highest PETCO2 were recorded for 5,159 thirty-second
      epochs. Although PtcCO2 and PETCO2 were available for 78.5 and 73.0% of epochs,
      respectively, at least one estimator was available for 92% of the epochs. One
      infant who would not tolerate a nasal sampling catheter had no PETCO2 data. For
      13 of 14 studies there was a relatively constant difference between PtcCO2 and
      PETCO2. The difference between PtcCO2 and PETCO2 was within 4 mm Hg in 63.9% of
      3,072 epochs. Across 14 studies, mean PtcCO2 exceeded mean PETCO2 by 2.8 +/- 3.0
      mm Hg, and it was within 4 mm Hg in 10 studies. In three subjects, PETCO2 was
      intermittently or consistently less than PtcCO2 because of tachypnea, increased
      physiologic dead space, or severe partial airway obstruction; in one subject
      PtcCO2 exceeded PETCO2 for undetermined reasons during one electrode application.
      The results of this study indicate that PtcCO2, as well as PETCO2, should be
      measured during pediatric polysomnography. By utilizing both PtcCO2 and PETCO2
      there was a 70% reduction in the number of epochs that could not be assessed for
      hypoventilation. For an individual subject or electrode application there was a
      constant, and usually close, relationship, between PtcCO2 and PETCO2.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256909
TI  - Comparison of peripheral chemoreceptor responses in monozygotic and dizygotic
      twin infants.
AB  - The peripheral chemoresponses of infant twin pairs were determined using a single
      breath hyperoxic stimulus. A total of 43 twin pairs of comparable gestation and
      birth weight were studied during sleep at a mean (SD) age of 8 wk (1.4) while
      alternately breathing either air or 16% oxygen in nitrogen. Infants responded to
      a single breath of 100% oxygen by a reduction in ventilation; the mean (SEM)
      reduction in air was 273 ml/min (10.6) and in 16% oxygen 560 ml/min (18.4).
      Within-pair variances were compared in 14 monozygotic and 28 dizygotic pairs
      utilizing combined responses (air + 16% oxygen) computed for measurements made in
      behavioral quiet sleep and in 9 monozygotic and 20 dizygotic pairs for whom data
      were complete in polygraphically confirmed quiet sleep. The variance of responses
      within dizygotic twin pairs was greater than in monozygotic pairs when expressed
      in ml/min: F ratio 4.11 (p = 0.005) for all data and F ratio 7.67 (p = 0.003) in
      quiet sleep. Expressed in ml/min/kg the difference was less significant: F ratio
      1.83 (p = 0.126) for all data and F ratio 3.46 (p = 0.039) in quiet sleep.
      Gender, birth weight, and birth order had no effect on these findings. This
      closer similarity of response in monozygotic twin pairs is explained by proposing
      a high degree of heritability for the response.

PMID- 8256910
TI  - Depressed ventilatory load compensation in sleep apnea. Reversal by nasal CPAP.
AB  - Abnormal inspiratory load compensation may be one factor leading to development
      of obstructive sleep apnea (OSA). Alternatively, abnormalities in ventilatory
      load compensation may be a consequence of the manifestations of OSA. This
      investigation was designed to determine if impairment of awake inspiratory load
      compensation exists in OSA and to determine if abnormalities in this parameter
      are reversible by nasal CPAP therapy. A new technique for assessment of awake
      inspiratory load compensation was devised to standardize the degree of
      ventilatory stimulation applied during load compensation assessment in each
      subject. This eliminates intersubject differences in degree of ventilatory
      stimulation during testing, which are inevitable with standard techniques and
      which have been shown to affect the measurement of load compensation. Inspiratory
      load compensation was assessed during resting room air ventilation and during
      steady state CO2 and exercise stimulation titrated to provide similar degrees of
      ventilatory stimulation in each subject. Impairment of awake inspiratory load
      compensation was found during all conditions in the patients with moderate to
      severe OSA studied compared with that in weight-matched control subjects.
      Normalization of awake inspiratory load compensation was observed after 4 wk of
      nasal CPAP therapy in five patients. These results indicate that impairment of
      awake inspiratory load compensation is a reversible consequence rather than a
      cause of OSA.

PMID- 8256911
TI  - Reflex activation of nasal secretion by unilateral inhalation of cold dry air.
AB  - Exposure to cold dry air induces rhinorrhea and other nasal symptoms in many
      persons. To evaluate whether this response involves a neurogenic component, we
      delivered a unilateral cold dry air (UniCDA) nasal challenge to volunteers with
      previously documented reactivity to cold dry air. We measured their nasal
      secretory responses bilaterally using small filter paper discs to absorb
      secretions from the nasal mucosa. UniCDA increased nasal secretion both
      ipsilateral (p < 0.001) and contralateral (p < 0.001) to the challenge when
      compared with control challenge. Topical atropine (0.225 mg), a muscarinic
      antagonist, inhibited ipsilateral secretion (p < 0.002) when given ipsilateral to
      UniCDA. When atropine was given contralateral to UniCDA, there was a trend toward
      reduction of contralateral secretion but no effect on ipsilateral secretion.
      Topical anesthesia with lidocaine given ipsilateral to UniCDA inhibited
      ipsilateral (p < 0.02) and contralateral (p < 0.05) secretion immediately after
      challenge. Topical anesthesia did not inhibit methacholine-induced nasal
      secretion. Thus, UniCDA stimulates reflex secretion both ipsilateral and
      contralateral to challenge which is inhibitable by interrupting either the
      efferent or the afferent arm of the reflex arc. This human in vivo model supports
      the importance of neural mechanisms in airway responsiveness to an environmental
      stimulus.

PMID- 8256912
TI  - Elemental composition of human airway surface fluid in healthy and diseased
      airways.
AB  - The fluid that covers the surface of conducting airways (airway surface fluid,
      ASF) is a critical component of one of the first defense mechanisms of the lung
      against microbial and other environmental insults. Despite its physiologic
      importance, ASF is one of the only fluids in the human body whose composition
      remains poorly defined and understood. Attempts to analyze ASF have been hampered
      greatly by the fact that it exists only as a very thin layer covering the mucosal
      surface of airway epithelia. To overcome some of these limitations, we have
      applied ultramicroanalytic techniques to microsamples collected in human airways
      in vivo. In contrast to previous thinking from studies on sputum samples, ASF
      collected from healthy airways contains much less Na and Cl (approximately 45%
      less) and much more K (around 600% more) than extracellular fluid or plasma
      (ECF), which shows that steep ion gradients exist across normal airway epithelia.
      These differences also show that ASF composition must be regulated and maintained
      by active electrolyte transport processes of airway epithelia and that it is not
      merely the evaporated residue of isotonic secretions or extracellular fluid
      exudate. However, in patients with sustained airway irritation, infection, or
      cystic fibrosis, we find that ASF composition appears to become more isotonic
      with respect to plasma and much more hypotonic in patients with asthma.

PMID- 8256913
TI  - Effects of endotoxin in vivo on endothelial and smooth-muscle function in rabbit
      and rat aorta.
AB  - In order to determine whether endotoxemia induced generalized defects in vascular
      contraction and endothelium-dependent relaxation, we studied the effect of in
      vivo endotoxin administration in Sprague-Dawley rats and New Zealand White
      rabbits on endothelial and arterial smooth-muscle responses of isolated thoracic
      aorta in vitro. Endotoxin treatment significantly decreased contractile responses
      to phenylephrine (PE), angiotensin II (AII), serotonin (5-HT), and potassium
      chloride. This effect was not altered by indomethacin or endothelial denudation.
      Treatment of vessels with NG-nitro-L-arginine (NNLA), an inhibitor of arginine
      dependent nitric oxide biosynthesis, or with methylene blue, an inhibitor of
      soluble guanylate cyclase, resulted in significant improvement of the contractile
      defect in endotoxin-treated vessels. The restorative effect of NNLA on
      contractile responses in endotoxin-treated aortic rings was similar in the
      presence or absence of an intact endothelium. Endothelium-dependent relaxation in
      response to acetylcholine, substance P, or the calcium ionophore A23187 was
      markedly impaired in vessels from endotoxin-treated rabbits, while endothelium
      independent relaxation in response to nitroprusside was similar in both groups.
      These results suggest that endotoxemia both induces basal, nonendothelial nitric
      oxide synthesis and impairs the agonist-stimulated release of endothelium-derived
      relaxing factor (EDRF). These findings may have mechanistic importance in the
      hemodynamic derangements of endotoxemia.

PMID- 8256914
TI  - Endothelin-1 in acute lung injury and the adult respiratory distress syndrome.
AB  - Endothelial damage is a hallmark of acute lung injury. Endothelial mediators may
      increase pulmonary vascular tone and induce pulmonary arterial muscularization,
      thereby contributing to the pulmonary hypertension seen with acute lung injury.
      We measured plasma levels and net pulmonary clearance of endothelin-1, a potent
      endothelium-derived vasoconstrictor peptide and smooth muscle mitogen, in 26
      patients with early acute lung injury, the adult respiratory distress syndrome,
      and pulmonary hypertension. Nineteen had another data collection at clinical
      improvement or worsening. Control subjects (n = 25) had no pulmonary hypertension
      or lung injury. Initial mixed venous and systemic arterial plasma endothelin-1
      levels were elevated (4.6 +/- 0.6 SEM and 4.9 +/- 0.6 pg/ml, respectively) as
      compared with control subjects (0.9 +/- 0.1 and 0.6 +/- 0.1 pg/ml). The systemic
      arterial/venous endothelin-1 ratio was 1.1 +/- 0.1 (0.7 +/- 0.1 in control
      subjects), indicating a reduction in normal net pulmonary endothelin-1 clearance.
      With clinical improvement, as compared with clinical worsening, mean plasma
      endothelin-1 levels, arterial/venous ratio, and pulmonary arterial pressure fell
      significantly towards normal. Thus, patients with acute lung injury have marked
      early increases in circulating plasma endothelin-1 levels, associated with
      abnormal pulmonary endothelin-1 metabolism. These abnormalities reverse in
      patients who recover. Through its actions, endothelin-1 could contribute to the
      pulmonary hypertension seen in acute lung injury.

PMID- 8256915
TI  - Differing effects of acute and prolonged alkalosis on hypoxic pulmonary
      vasoconstriction.
AB  - Animal studies and clinical pediatric practice have shown that acute alkalosis
      attenuates hypoxic pulmonary vasoconstriction (HPV). However, increased
      intracellular pH appears to enhance pulmonary vasoreactivity. We therefore
      hypothesized that prolonged alkalosis augments HPV. This study compares the
      effects of acute and prolonged alkalosis on HPV in isolated perfused lungs of 1
      month-old lambs (n = 5) and the hypoxic responses of 300- to 500-microns diameter
      segments of pulmonary arteries (n = 7) from mature cats at control pH and after
      30 min of alkalosis. In isolated lamb lungs, normocarbic (5% CO2) hypoxia (4% O2)
      increased the total pressure gradient (delta PT) by 6.0 +/- 2.7 (SEM) mm Hg (p <
      or = 0.05). Acute hypocarbia (3% CO2) increased the perfusate pH to approximately
      7.52 and significantly decreased the hypoxic delta PT to normocarbic, normoxic
      (28% O2) levels. Subsequent exposure to normoxia (while maintaining alkalosis)
      further decreased delta PT. However, re-exposure to hypoxia after 60 min of
      normoxic alkalosis significantly increased delta PT by 11.6 +/- 1.6 mm Hg (p < or
      = 0.05) to a level similar to that seen during normocarbic hypoxia. The increased
      hypoxic reactivity (i.e., change in pressure between normoxia and hypoxia) during
      prolonged alkalosis was due to enhanced HPV of the small vessels within the
      middle segment of the pulmonary circuit, as defined by an inflow-outflow
      occlusion technique (p < or = 0.05). The occlusion data also suggested that most
      of this increase occurred in small arteries. Moreover, the hypoxic response of
      isolated small arteries from the cat was increased almost threefold (p < or =
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256917
TI  - alpha 1-Proteinase inhibitor, elastase activity, and lung disease severity in
      cystic fibrosis.
AB  - The potential role of neutrophil elastase in exacerbating pulmonary infection and
      tissue damage in cystic fibrosis (CF) has led to proposals for treatment of lung
      disease in CF with the elastase inhibitor, alpha 1-proteinase inhibitor (alpha
      1PI). Reports that alpha 1PI is inactivated in the CF lung suggest that the
      effectiveness of alpha 1PI therapy depends on the quantity of elastase present
      and the extent of alpha 1PI inactivation, both of which are expected to vary with
      disease severity. In this study we assessed the elastase-alpha 1PI profile in
      sputum and plasma from CF patients with various degrees of pulmonary involvement.
      Levels of active elastase in sputum samples increased with severity of pulmonary
      disease (F ratio = 5.63, p < 0.01), as did sputum levels of alpha 1PI (F ratio =
      4.88, p < 0.01). A positive correlation was observed between sputum levels of
      active elastase and alpha 1PI (r = 0.68, p < 0.005). Plasma alpha 1PI levels were
      also elevated in CF patients compared with control subjects (p < 0.005),
      indicating a compensatory increase in plasma and sputum levels of alpha 1PI in
      response to increased elastase load. Molar levels of total immunogenic neutrophil
      elastase were, on average, 12 times higher than alpha 1PI in CF sputum. These
      results suggest that the major contributor to the elevated levels of active
      elastase observed in the CF lung is an increase in elastase release rather than
      inactivation of alpha 1PI.

PMID- 8256916
TI  - Effects of positive end-expiratory pressure and body position on pressure in the
      thoracic great veins.
AB  - Positive end-expiratory pressure (PEEP) commonly decreases cardiac output. The
      major cause of this is believed to be decreased venous return due to increased
      right atrial pressure. We hypothesized that when the lungs were hyperinflated
      they could also restrict venous return by directly compressing the thoracic vena
      cavae. We measured the longitudinal distribution of pressure in the thoracic vena
      cavae of 10 dogs on and off 10 mm Hg PEEP, in the supine (S), prone (P), right
      lateral (RL), and left lateral decubitus (LL) positions. In the superior vena
      cava (SVC) both on and off PEEP, and in the inferior vena cava (IVC) off PEEP,
      pressure fell uniformly from the thoracic inlet to the right atrium. However, in
      the IVC on PEEP, intravascular pressure fell abruptly by up to 5 mm Hg. This
      pressure drop occurred in a discrete (1 to 2-cm) segment of the IVC, suggesting a
      localized increased in extravascular surface pressure. When this pressure
      inflection was present, changes in right atrial pressure had no effect on
      pressure in the IVC upstream of the inflection, consistent with a "vascular
      waterfall." These observations were most prominent in the LL, least common in the
      RL, and variably present in the P and S positions. Occlusion of the right
      bronchus intermedius prior to PEEP (preventing right lower, middle, and accessory
      lobe inflation) prevented the appearance of the pressure inflection during PEEP
      in the LL but not in the S or P positions. We conclude that PEEP impedes venous
      return partly by direct compression of the IVC, predominantly in positions in
      which the IVC is non-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256918
TI  - Radiation pneumonitis. Bronchoalveolar lavage assessment and modulation by a
      recombinant cytokine.
AB  - A common side effect of radiotherapy is the development of fibrosis in the
      irradiated tissue. To study the mechanisms of this fibrogenic response, we
      developed a model system of whole-lung radiation in the rat and studied the
      evolution of injury by assessment of the cells and protein recovered by lavage.
      Once the pattern of injury was known, we attempted to modulate this reaction by
      administering the cytokine interferon-gamma (IFN-gamma). Rats received 15 Gy
      radiation to the whole thorax and were studied by lung lavage at intervals of 1
      to 35 days after radiation. The effect of radiation was an initial (24 h) leak of
      protein, unaccompanied by cellular alterations, that resolved by 48 h. This was
      followed 2 wk later by a phase of inflammatory cell recruitment and more
      significant protein leak. A third phase of increase in inflammatory cells and
      further increase in protein flux was noted at Day 35. A significant cellular
      infiltrate was seen in lung sections obtained from animals treated in parallel
      experiments. IFN-gamma was given by osmotic pump from Day 0 to Day 35. This
      treatment significantly attenuated the PMN recruitment and protein leak (p <
      0.002 and 0.01, respectively) at Days 25 and 35. Histologic sections demonstrated
      reduced alveolar cellularity and exudate at Day 25 (p < 0.05); however,
      significant numbers of inflammatory cells and exudate were present in irradiated
      and IFN-gamma-treated animals at Day 35. These data indicate that inflammatory
      cell recruitment may play a role in the lung injury following radiation.
      Furthermore, these preliminary data indicate that a cytokine blocks this
      reaction.

PMID- 8256919
TI  - The effects of inhaled interferon gamma in normal human airways.
AB  - Recent studies suggest that cytokines such as recombinant interferon-gamma (rIFN
      gamma) may play a role in the treatment of certain respiratory conditions
      associated with infection and inflammation. This study was designed to determine
      if rIFN-gamma could be delivered effectively in a group of normal human
      volunteers. The effectiveness of the inhaled delivery system was demonstrated by
      the recovery of free IFN-gamma in bronchoalveolar lavage (BAL) fluid and
      macrophage (M phi) expression of IP-10, an IFN-gamma-inducible molecule, after
      therapy but not at baseline. IL-1 beta, but not IL-8, gene transcripts also
      showed evidence for up-regulation after rIFN-gamma therapy. Compared with
      baseline, inhaled rIFN-gamma did not significantly alter clinical symptom scores,
      spirometry, morning peak expiratory flow rate (PEFR), or the response to
      methacholine. Of interest, the evening PEFR increased significantly (p = 0.02),
      from 568 +/- 36 L/min at baseline to 584 +/- 33 L/min after inhaled rIFN-gamma.
      Although there was no significant change in total white cell count in BAL fluid,
      the cellular composition did demonstrate a significant decrease in percentage of
      alveolar M phi (p = 0.02) and an increase in percentage of lymphocytes (p = 0.02)
      after rIFN-gamma. There were no histologic differences seen in bronchial biopsy
      specimens, and there was no evidence for up-regulation of ICAM-1 or HLA-DR
      expression after rIFN-gamma. We conclude that, in normal persons, rIFN-gamma can
      be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma
      appear to be warranted for certain pulmonary diseases.

PMID- 8256920
TI  - T-lymphocytes with gamma delta+ V delta 2+ antigen receptors are present in
      increased proportions in a fraction of patients with tuberculosis or with
      sarcoidosis.
AB  - T-lymphocytes with T-cell antigen receptor (TCR) comprising a gamma chain and a
      delta chain (gamma delta+ T cells) are believed to be involved in the immune
      reaction to mycobacterial antigens, and they have been found in increased
      proportions in sarcoid patients. We evaluated the proportions of gamma delta+ T
      lymphocytes and of two major gamma delta+ subpopulations, the V delta 1+ and the
      V delta 2+ T-cell subsets, in 10 normal blood donors, in 15 patients with
      tuberculosis (TB), seven of whom had pleural effusion (PE), and in 12 patients
      with pulmonary sarcoidosis (PS), nine of whom underwent bronchoalveolar lavage
      (BAL). T-cell subsets were evaluated in peripheral blood (PBL) of all subjects
      and in PE from patients with TB and in BAL from patients with PS. Compared with
      normal blood donors, patients with TB had increased proportions of PBL CD3+ gamma
      delta+ T cells (6 +/- 1% versus 14 +/- 3% of CD3+ T cells, p < 0.05) because of
      the presence of four patients who had an increase (respectively, 18.3, 22.0,
      24.2, and 35.4% of CD3+ T cells) of gamma delta+ T cells. In patients with TB and
      PE, gamma delta+ T cells were 7.9 +/- 2.7%, a value not different from that in
      the tubercular PBL and in normal PBL. Although patients with PS had proportions
      of PBL gamma delta+ T cells (9.2 +/- 3.4%) similar to those in normal PBL, two
      patients had increased (35 and 31%) PBL gamma delta+ T-lymphocytes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8256921
TI  - Resection of pulmonary metastases.

PMID- 8256922
TI  - Adhesion molecules in the lung. An overview.
AB  - Several distinct cell adhesion molecule families have recently been identified
      and found to be important in the inflammatory response and for epithelial and
      endothelial homeostasis. The integrin family of adhesion molecules functions in
      both cell-matrix and cell-cell interactions, whereas the cadherins serve as
      important cell-cell receptors for maintenance of epithelial integrity. The
      leukocyte integrins, selectins, members of the immunoglobulin supergene family,
      and specific carbohydrates mediate adhesive interactions between leukocytes and
      endothelial cells. The mechanisms of leukocyte-epithelial adhesion are less well
      understood, but integrins and members of the immunoglobulin supergene family are
      also involved. The role of these molecules in pulmonary structure and
      inflammation is currently being actively explored. Further knowledge of these
      interactions, and the interplay of adhesion molecules, cytokines, and
      chemoattractants is likely to lead to novel therapeutic modalities in
      inflammatory diseases of the airway and lung parenchyma. In this overview, the
      families of adhesion molecules will be summarized, and their relevance for
      pulmonary structure and inflammation will be discussed.

PMID- 8256923
TI  - Identification and characterization of novel airway epithelial integrins.
AB  - Integrins are heterodimeric glycoproteins that mediate cell-to-matrix and some
      cell-to-cell interactions. Recent evidence underscores the important roles of
      these receptors in signaling machines that transduce positional information into
      complex changes in cell behavior. As such, integrins have been shown to play
      critical roles in cell growth, differentiation, and migration. Most cells express
      multiple members of this family, but the integrin repertoire of any given cell
      appears to be highly tissue- and cell-type-specific. We have used the homology
      based polymerase chain reaction to identify known and novel integrin subunits in
      airway epithelial cells. With this technique we have identified three novel
      integrin subunits that participate in the formation of at least four novel
      integrin heterodimers. The best characterized of these, alpha v beta 6, is a
      receptor for the extracellular matrix protein fibronectin, and appears to be
      expressed only in terminally differentiated mucosal epithelial cells. The novel
      alpha subunit, alpha 9, forms a heterodimer with the known beta subunit, beta 1,
      in some epithelial cell lines. Elucidatation of the specific roles these
      receptors play in airway health and disease will likely provide unique insights
      into both the biology of integrins and the biology of the airway epithelium.

PMID- 8256924
TI  - Mechanisms of neutrophil and eosinophil accumulation in vivo.
AB  - The accumulation of leukocytes into tissues is a characteristic feature of
      inflammatory reactions. This process is triggered by chemical signals generated
      in a tissue in response to an inflammatory stimulus e.g., invading microbes,
      other foreign organisms, allergens, or damaged tissue cells. The mechanisms
      involved in neutrophil and eosinophil accumulation in vivo are complex and
      dependent on an initial interaction between the leukocytes and the microvascular
      endothelial cells. This response is regulated by the coordinated expression
      and/or activation of leukocyte and endothelial cell adhesion molecules. The
      precise mechanisms that control the selective accumulation of eosinophils, as
      opposed to neutrophils, in certain inflammatory reactions (e.g., in IgE-mediated
      allergic reactions) remain unclear. This may be explained partly by the
      generation of eosinophil-specific inflammatory mediators and activation of
      selective adhesion pathways such as the VLA-4/VCAM-1 interaction. Although the
      neutrophil and eosinophil have distinct roles in host defense, they have been
      implicated in the pathogenesis of a number of inflammatory disorders. Thus, a
      better understanding of the events mediating and regulating neutrophil and
      eosinophil accumulation in vivo will be of considerable value in the development
      of therapeutic strategies for inflammatory disease states.

PMID- 8256925
TI  - Molecular mechanisms mediating lymphocyte recirculation, inflammation, and
      metastasis formation.
AB  - A multitude of glycoproteins expressed in cellular membranes have been identified
      by monoclonal antibodies. Besides mediating transient cell/cell contacts, these
      molecules unequivocally function as receptor structures capable of transmitting
      signals for cell growth and differentiation. They are the central determinators
      of local immune responses, and they allow an adjustment of the recirculating
      immunocompetent cells to their respective local microenvironments. Given that
      receptor/ligand interactions are characteristic of particular in vivo sites,
      knowledge of structural and functional features of adhesion receptors can provide
      new prospects for a more targeted clinical immune intervention.

PMID- 8256926
TI  - Adhesion molecules and cytokine production.
AB  - The exchange of cross-talks between cells relies on soluble factors or direct
      cell-cell contact. Soluble factors increase the expression of cell surface
      molecules that activate adjacent cells by direct contact to produce cytokines. In
      the lung, dendritic cells are potent inducers of T-cell proliferation, and the
      interaction between the two leads to the production of high amounts of TNF alpha
      and TNF beta. Of the molecules involved in these biologic functions, LFA-3,
      CD11c, and the combination of beta 1 and beta 2 integrins are the most efficient.
      However, blocking TNF alpha or TNF beta production does not affect the
      alloreaction. The interaction between activated T cells and monocytes resulted in
      a large production of IL-1 beta. In this reaction, CD69, CD2, and the beta 2
      integrins (CD11a, b, c, and CD18) and also other molecules such as a 25- to 35-kD
      glycoprotein play an important part. Finally, interaction between monocytes and
      fibroblasts leads to the production of large amounts of collagenase and PGE2 by
      fibroblasts. Cell-associated IL-1, particularly IL-1 alpha and membrane-bound TNF
      alpha, can also play a crucial role in the process of cell-cell interaction. This
      interaction may be controlled by inhibitors to IL-1 and TNF.

PMID- 8256927
TI  - Cell adhesion molecules and the bronchial epithelium.
AB  - The bronchial epithelium is the major barrier between the host and the provoking
      antigens in bronchial asthma. Recent studies have indicated that the epithelium
      is a truly stratified structure, with the superficial columnar cells depending on
      the underlying basal cells for anchorage. Only columnar cells are shed into
      bronchial lavage fluid. The epithelium is more fragile in asthma and more cells
      are lost in clusters. Desmosomes appear to be the major structural adhesion
      mechanism at the plane of cleavage between the columnar cells and the basal
      cells. The alpha 6- and beta 4-integrins, which contribute to hemidesmosomes and
      anchor cells to the underlying basement membrane, are expressed solely by basal
      cells. The apical aspects of the columnar cells are sealed by tight and
      intermediate junctions. There is constitutive expression of ICAM-1 and E-selectin
      in the vasculature of the bronchial mucosa, and ICAM is also present within the
      epithelium. These findings indicate that the bronchial epithelium is a complex
      structure that, as a mucosal surface, has constitutive expression of inflammatory
      cell adhesion molecules to serve normal leukocyte traffic.

PMID- 8256928
TI  - Laparoscopic cholecystectomy in critically ill cardiac patients.
AB  - From August 1989 to January 1993, the authors performed laparoscopic biliary
      operations in 900 patients, 13 of whom had severe cardiac dysfunction. Nine
      patients were Goldman Class IV, and four patients were Goldman Class III. Three
      patients had recent myocardial infarction, five patients were known to have low
      left ventricular ejection fractions (10%, 21%, 25%, 26%, and 30%), one had severe
      myocardial ischemia, one had severe congestive heart failure, and one was in
      profound shock. Nine patients underwent successful laparoscopic cholecystectomy.
      Laparoscopic cholecystostomies were performed in three patients. One operation
      was converted to an open cholecystectomy. There was one death within 30 days of
      surgery. With appropriate hemodynamic monitoring and adequate perioperative
      support of cardiac function, laparoscopic cholecystectomy can be performed safely
      for acute cholecystitis in patients with severe cardiac disease. When compared
      with historical controls, laparoscopic cholecystectomy appears to be safer than
      open cholecystectomy.

PMID- 8256929
TI  - Inhibition of intra-abdominal adhesions: fibrin glue in a long term model.
AB  - Fibrin glue is being used more frequently to assist in the control of surgical
      bleeding in the abdominal and thoracic cavities. Prior investigation at this
      institution has indicated that fibrin glue actually inhibits adhesion formation
      in the peritoneal cavity of rats up to the first week postoperatively. To
      ascertain whether this protective effect is borne out in the long term, a
      randomized study was performed in 42 rats. As in the initial study, bilateral
      circular peritoneal-muscular defects were created to induce adhesion formation.
      The right-sided defects were closed linearly with interrupted sutures, thus
      closing the peritoneum, and the left-sided defects were closed with a continuous
      suture placed circumferentially, leaving the peritoneal defect open. The rats
      were randomized to two groups. In 21 animals, the abdomen was closed with no
      further treatment. In the other 21 animals the defects were covered with fibrin
      glue made from 0.2 mL of human fibrinogen (31.5 g/L) from cryoprecipitate and 0.2
      mL of bovine thrombin and calcium. All rats were killed at 30 days, and adhesions
      were graded on a scale of 0 to 4 by a blinded observer. In the control group, 15
      of 21 rats had high grade adhesions to the closed defect compared with 3 of 21 in
      the experimental (fibrin glue) group (P = 0.0003). For the left-sided lesions, 16
      of 21 animals in the control group had high grade adhesions compared with 2 of 21
      animals in the experimental group (P = 0.0004).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256930
TI  - Susceptibility of intra-abdominal isolates at operation: a predictor of
      postoperative infection.
AB  - Antimicrobial resistance of operative site flora was correlated with
      postoperative infection in 175 patients undergoing operation for intra-abdominal
      sepsis: Diagnoses for study patients were acute or gangrenous appendicitis in 48
      (27%), complicated appendicitis in 98 (56%), perforated viscus other than
      appendix in 21 (12%), and eight (5%) had other intra-abdominal infections. One
      hundred thirty-six (78%) patients were males. The average age was 33 +/- 14
      years, average number of hospital days was 11.6 +/- 13.5, and average number of
      days on antibiotics was 6.9 +/- 2.5. Overall recovery without infection was 75
      per cent (131/175). Analysis of susceptibility of 939 intraoperative isolates
      indicated a significant relationship (P = 0.0002) between resistance to the
      empiric antimicrobials received and postoperative infection. Of 131 patients with
      resolution of the intra-abdominal infection, 57 (44%) had resistant isolates
      while 36 (82%) of 44 patients with postoperative infectious complications had
      resistant isolates. Streptococcus Group D, Escherichia coli, and Bacteroides
      fragilis were the most prevalent resistant organisms isolated from both intra-
      and postoperative cultures. Other variables that were significantly different
      between those without complications and those who had complications were,
      respectively: average age 31 versus 38; admission WBC 14.5 versus 16.7; and
      diagnosis, acute appendicitis 28 per cent versus 2 per cent. A stepwise logistic
      regression analysis confirmed the predictive value of intraoperative isolate
      resistance, age, and admission WBC, in that order, on outcome.

PMID- 8256931
TI  - Superoxide dismutase and allopurinol improve survival in an animal model of
      hemorrhagic shock.
AB  - We studied the efficacy of resuscitation with antioxidants in an animal model of
      hemorrhagic shock. Male Sprague-Dawley rats were anesthetized, and 27 mL/kg of
      blood was withdrawn from the carotid artery over 2 minutes. The animals remained
      in hemorrhagic shock for 45 minutes, followed by 1 hour of resuscitation.
      Experimental groups were as follows: 1) 15,000 u/kg superoxide dismutase (SOD) in
      54 mL/kg lactated Ringer (LR); 2) 175,000 u/kg catalase (CAT) in LR; 3) 15,000
      u/kg SOD+175,000 u/kg CAT in LR; 4) allopurinol in LR; 5) deferoxamine bound to
      pentafraction (DFO), 27 mL/kg; 6) pentafraction alone; and 7) LR alone. Compared
      with resuscitation with LR alone, SOD and allopurinol improved survival over 72
      hours, P < 0.05. Survival with SOD+CAT was not different from LR alone.
      Deferoxamine bound to pentafraction did not increase survival over that with
      pentafraction alone. CAT had increased mortality compared to LR, P < 0.01. The
      efficacy of both SOD and allopurinol in decreasing mortality suggests the
      importance of superoxide radicals after hemorrhagic shock and resuscitation.
      These and other antioxidants are potential therapeutic agents in the clinical
      setting of trauma and hemorrhagic shock.

PMID- 8256932
TI  - Pulmonary sequestration: 17-year experience at UCLA.
AB  - Pulmonary sequestration is a complex anomaly involving the pulmonary parenchyma
      and its vascularity. From 1975 to 1992, 10 cases have been treated at the UCLA
      Medical Center. The ages of the seven females and three males were bimodal, the
      median age of the seven children was 29 days (range 1 day-6 years); it was 32
      years (range 28-39) for the three adults. One child was delivered by cesarean
      section for fetal distress and another was born at 29 weeks gestation. Symptoms
      included: recurrent pneumonia (5), respiratory distress (5), hemoptysis (2),
      stridor (1), and pleuritis (1). Chest radiographs were consistent with
      sequestration in seven patients and diaphragmatic hernia in another, but
      incorrectly diagnosed one diaphragmatic eventration and one pulmonary varix.
      Computed tomographs suggested sequestration in five patients, but mistakenly
      interpreted a pulmonary varix in one case. Angiography, ultrasonography, and
      magnetic resonance imaging were infrequent investigative studies and yielded
      variable results. All patients underwent thoracotomy and lobectomy without
      morbidity or mortality. Five had intralobar and five had extralobar
      sequestration. All adults had intralobar sequestration. Two had aberrant
      subdiaphragmatic arterial vessels. Eight had vessels originating from the
      descending thoracic aorta. Nine patients are asymptomatic at six months to 10
      years follow up. The 29-week-old premature infant died 30 days postoperatively
      due to necrotizing enterocolitis. Pulmonary sequestration remains an uncommon
      entity. The radiologic investigations that provide the most information are the
      chest radiography and computed tomography. Definitive diagnosis is made at
      thoracotomy. Pulmonary sequestrations are resected with excellent results by the
      trained thoracic surgeon who is aware of the unusual vascular connections.

PMID- 8256933
TI  - Radical resection combined with liver transplantation for foregut tumors.
AB  - Between February 1984 and July 1992, six adults with advanced pancreatic
      adenocarcinoma (n = 1), pancreatic neuroendocrine tumor (n = 2), and
      cholangiocarcinoma (n = 3) underwent radical foregut resections (n = 3) or
      radical pancreaticoduodenectomy (n = 3) combined with liver transplantation. The
      major postoperative complications included diarrhea (n = 4),
      pancreaticojejunostomy leak (n = 3), infection (n = 7), malnutrition (n = 3),
      refractory ascites (n = 2), and late hepatic artery thrombosis (n = 1). Tumor
      recurrence occurred in one patient. The actuarial survival for the group is 82
      per cent at 1 year and 55 per cent at 2 years. The results demonstrate that
      radical pancreaticoduodenectomy/foregut resections combined with liver
      transplantation offer potential surgical cure of malignancies involving these
      organs. However, the procedure is formidable, with frequent complications.

PMID- 8256934
TI  - Iatrogenic vascular trauma associated with intra-aortic balloon pumping:
      identification of risk factors.
AB  - The most important noncardiac consequence of use of the intra-aortic balloon pump
      (IABP) is associated iatrogenic vascular trauma. A retrospective analysis was
      undertaken of all patients at our institution (n = 90, mean age 60 years) who had
      insertion of an IABP over a 10-year period to assess the possibility of
      preoperative identification of patients at high risk of IABP associated vascular
      injury. Catheters were introduced via the common femoral artery (n = 84; 30
      percutaneous, 4 open Seldinger technique, 50 via a dacron sleeve), external iliac
      artery (n = 2), and ascending aorta (n = 4). Thirty patients (33.3%) developed
      one or more complications, with 25 vascular complications, six major septic
      complications, and four deaths. Variables identified as significant risk factors
      for IABP complications were female gender (P < 0.01) and concomitant peripheral
      vascular disease (P < 0.05). Site of insertion, method or difficulty of
      insertion, age, duration of counterpulsation, and use of anticoagulation and
      antibiotics did not significantly affect the incidence of vascular complications
      (P > 0.05). In conclusion, prior to cardiac surgery, we recommend screening for
      peripheral vascular disease to identify patients at increased risk of
      complications should IABP counterpulsation be required. Ankle/brachial systolic
      pressure indices may be used to detect subclinical disease.

PMID- 8256935
TI  - Pseudoaneurysms of the aorta after cardiac surgery or chest trauma.
AB  - Between March 1982 and June 1992, 17 patients (age: 21-76 years) were diagnosed
      with pseudoaneurysm of the thoracic aorta (PTA). Four PTAs developed post-trauma
      while 13 developed after aortic or cardiac surgery. Unusual presentations
      included: dyspnea, hoarseness, dysphagia, massive hemoptysis (2 degrees to
      aortobronchial fistula), massive hematemesis (2 degrees to aorto-esophageal
      fistula), superior vena cava syndrome, paralyzed right hemidiaphragm, and herald
      bleeding from the sternotomy. The interval between initial operation and
      recognition of PTA varied from three months to eight years while the four
      posttraumatic PTAs presented 5 to 26 years postinjury. The sites of postoperative
      PTA were: the aortotomy (3), proximal vein graft anastomosis (4), aortic
      cannulation site (2), and distal anastomosis of ascending aortic graft
      replacement (4). Aortography was very sensitive, outlining the false aneurysm in
      13/13. Five patients had transesophageal echo-cardiography with one false
      negative. Seven patients died (41%), three from postoperative PTAs from massive
      hemorrhage intraoperatively and four from sepsis and multiorgan failure following
      repair. We conclude that patients who have previously had aortic or cardiac
      surgery or a history of blunt chest trauma presenting with unusual
      cardiorespiratory symptoms should be aggressively evaluated for PTA. Due to the
      magnitude of the operative problems encountered, repair of PTA is associated with
      a significantly high rate of mortality.

PMID- 8256936
TI  - Laparoscopic inguinal hernia repair results: 131 cases.
AB  - Since its introduction, laparoscopic inguinal hernia has been plagued with
      multiple technical problems. A series of 131 laparoscopic inguino-femoral hernia
      repairs is presented. The technique used was an original transabdominal pre
      peritoneal approach using a SurgiPro mesh with two technical variations. In the
      beginning, this procedure was only offered to patients less than 50 years of age.
      These guidelines were eliminated as the study progressed. For our first 10 cases,
      our average operating time was 1 hour and 39 minutes. For the last 40 cases, it
      averaged 63 minutes. All but four patients were discharged the same day. Ninety
      six per cent of all patients felt minimal pain or discomfort within 72 hours.
      Four per cent felt pain or discomfort until the tenth post-operative day. All
      patients were ambulatory the day of surgery, and 94 per cent of all patients
      resumed regular activities before the tenth postoperative day. No significant
      morbidity and no mortality were identified with the exception of five
      postoperative inguinal seromas, which were successfully aspirated. No recurrence
      was demonstrated, but this series is clearly insufficient to establish a rate of
      recurrence. The cost of these procedures appeared to be higher than for a
      conventional repair; however, it has recently been reduced. The procedures remain
      difficult, but the rate of recovery for these patients is shown to be
      significantly improved. The superiority of this procedure over its open
      counterpart has not yet been proven.

PMID- 8256937
TI  - Medical and economic consequences of gang-related shootings.
AB  - Treatment costs for victims of gang violence have fueled the withdrawal of
      hospitals from trauma networks. Not included in such tallies are the medical
      resources that these seriously ill and medically indigent patients divert from
      other areas. We examined the surgical care requirements, costs incurred, and
      outcomes at a Level I trauma center. Local law enforcement records were matched
      with hospital admissions over a 1-year period to identify with hospital
      admissions over a 1-year period to identify casualties of gang violence. Of 191
      gunshot wound admissions, 107 (56%) were gang related. The majority were males
      (92%); ages ranged from 14 to 50 and trauma scores from 1-16. Eighty-six were
      admitted during periods of minimum staffing (7:00 PM to 7:00 AM), pre-emptying
      the use of limited resources for other medical/surgical emergencies. Fifty-eight
      (54%) needed emergency surgery: laparotomy (38), thoracotomy (5), and
      neck/extremity (15). Forty required multiple surgical procedures, and eight
      patients required nine subsequent surgeries. There were two deaths. Average
      hospital stay ranged from 1 to 180 days; inpatient days totalled 1003, 270 of
      which were spent in the ICU. Total charges neared +2.0 million. Ninety-four
      patients (88%) were medically indigent. On discharge, 75 patients were disabled,
      six permanently. We conclude: 1) Gang activity caused the majority of gunshot
      wounds at our trauma center; 2) multiple injuries predominated, requiring
      extensive ICU use; 3) the combination of indigent patients and high hospital
      costs underestimate the financial burden as valuable resources are diverted from
      other areas; 4) subsequent community costs include rehabilitation and chronic
      care.

PMID- 8256938
TI  - Emergency thoracotomy with lung resection following trauma.
AB  - Over a 7-year period, 9443 trauma patients were evaluated with 2934 (31%)
      sustaining chest trauma. Of these, 347 (12%) patients required thoracotomy, with
      12 patients undergoing emergency lung resection. Mean age was 23.1 years with
      mean Injury Severity Score of 32. Mechanism of injury was blunt in three (25%),
      gunshot wound in seven (58%), and stab wound in two (17%). Associated injuries
      included head injury in two (17%), intra-abdominal injury requiring laparotomy in
      four (33%), cardiac injury in three (25%), and great vessel injury in one (8%).
      Indications for operation included persistent hemorrhage in 11 and suspected
      tracheobronchial disruption in one. Non-anatomic lung resection was performed in
      five patients, lobectomy in three patients, and pneumonectomy in four patients.
      Overall mortality was 33 per cent: 20 per cent for non-anatomical lung resection,
      33 per cent for lobectomy, and 50 per cent for pneumonectomy. All survivors fully
      recovered except for one patient with an associated head injury. Our experience
      supports the selective use of lung resection, including pneumonectomy, to
      immediately control hemorrhage and to impact survival in severe chest trauma.

PMID- 8256939
TI  - Reduction of wound infection in high-risk surgical patients.
AB  - During a 9-year period, 183 consecutive patients underwent total colectomy and
      the endorectal ileal pull-through procedure (ERIPT) for ulcerative colitis (UC)
      (n = 156), familial polyposis (n = 25), or Hirschsprung's disease (n = 2). The
      average age was 29.4 years (range 7.1-59.1 years). All patients with UC were
      steroid-dependent at the time of operation. Two groups were retrospectively
      reviewed based on the management of their midline abdominal wounds. Ninety
      consecutive patients underwent the ERIPT procedure between 1983 and 1987 with
      stapled skin closure and perioperative intravenous antibiotics (group 1A).
      Between 1988 and 1992, 93 patients had abdominal wall closure in the same manner,
      however, the wounds were probed daily in four to six sites for the first five
      postoperative days with a Q-tip moistened with 2 per cent aqueous mercurachrome
      solution (group 2A). Approximately four months after ERIPT, ileostomy closure was
      performed on 176 of the patients, of whom 89 had no wound probing (group 1B), and
      87 had probing (group 2B). Following colectomy and the ERIPT procedure, 22/90
      group 1A patients (24.4%) and 4/93 group 2A patients (4.3%) developed wound
      infections. Following ileostomy closure only 3/89 (3.4%) group 1B patients and
      1/87 (1.2%) group 2B patients developed wound infections. No group 2A or B
      patients required wound packing, and none had prolonged hospitalization. In
      contrast, 17 group 1A patients spent more than 1 extra day of hospitalization
      (mean 2.8 days) and required wound packing a mean of 22.6 days after hospital
      discharge. This wound infection rate is significantly lower for group 2A versus
      1A patients (P < 0.0001, ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8256940
TI  - Staged Zenker's diverticulectomy with cervical esophagostomy and secondary
      esophagostomy closure for treatment of massive diverticulum in severely
      debilitated patients.
AB  - Cricopharyngeal myotomy and diverticulectomy have become the standard therapy for
      the vast majority of patients with pharyngoesophageal diverticula. Potential
      complications from this approach, however, may be devastating in debilitated,
      elderly patients with massive Zenker's diverticula. Because of potentially fatal
      complications, we advocate a staged approach to treat debilitated patients with
      massive Zenker's diverticula. In the first stage, myotomy, diverticulectomy, and
      cervical esophagostomy are performed, and a gastric feeding tube is positioned
      through the esophagostomy. After recovery from pulmonary complications and
      nutritional improvement, the feeding tube is removed and the esophagostomy is
      closed. From 1987 to 1992, we treated five severely debilitated patients, four
      men and one woman with massive Zenker's diverticula, with this novel approach.
      Age of the patients averaged 80 years, range 58 to 93. All patients had symptoms
      of pulmonary aspiration requiring multiple hospitalizations for life-threatening
      pneumonia. Three patients had severe malnutrition associated with major weight
      loss and cachexia. All patients underwent first stage repair without morbidity or
      mortality. After an average of 7 weeks, patients had significant nutritional
      improvement and the esophagostomy was closed. Local wound care adequately treated
      one wound infection after esophagostomy closure. Although myotomy and
      diverticulectomy are safe procedures, a staged approach, diverticulectomy and
      cervical esophagostomy, followed by esophagostomy closure, is advocated for the
      elderly, severely debilitated patient with massive Zenker's diverticulum.

PMID- 8256941
TI  - Small bowel obstruction after abdominal aortic surgery.
AB  - Early postoperative small bowel obstruction (SBO) is a known complication of
      intestinal surgery, but its frequency, etiology, and morbidity after abdominal
      aortic procedures have not been reported. To study this complication, the records
      of 1475 patients who had an abdominal aortic operation for aneurysmal (n = 818)
      or occlusive (n = 657) disease on a private surgical service from 1963 to 1990
      were reviewed. Forty-four patients (2.9%) developed a postoperative SBO. Small
      bowel obstruction occurred from 4 to 28 (mean 6) days postoperatively. All
      patients were treated with nasogastric suction. Eighteen of the 44 (41%) required
      reoperation from 6 to 30 (mean 14.2) days after the initial aortic procedure. All
      18 had lysis of adhesions, and two required small bowel resections. There were no
      bowel infarctions and no late graft infections. Overall mortality was 5 per cent,
      and morbidity was 16 per cent. Incidence of pancreatitis in the entire series was
      0.5 per cent, and incidence of colonic ischemia in the aneurysm group was 0.9 per
      cent. We conclude that 1) Early postoperative small bowel obstruction is an
      unusual complication of aortic surgery but is more frequent than other
      gastrointestinal complications such as intestinal ischemia and pancreatitis; 2)
      Management principles are similar to those for early postoperative bowel
      obstruction following other procedures; 3) Reoperation is required in nearly half
      of patients, particularly when SBO does not resolve within 2 weeks.

PMID- 8256942
TI  - The contributions of patient factors, physician delay, and tumor biology to the
      outcome of gastric cancer.
AB  - Patients with gastric cancer were presenting at advanced stage to our hospital.
      We were concerned that patient or physician controlled factors might have been
      responsible. A retrospective review of 49 analytic gastric cancer cases
      presenting to UCIMC between 1984 and 1989 was conducted. Twenty-four patients
      were determined to have gastric cancer as outpatients, with a median duration of
      symptoms of 4 months. The other 25 patients had initial physician contact in the
      emergency room, with a median duration of symptoms of only 1.5 months (P =
      0.007). Minority ethnic groups were urgently admitted more frequently than
      Caucasians (P = 0.004). Multivariate analysis revealed that the worst prognostic
      factors for gastric cancer were urgent admission of Caucasians and Asians (P =
      0.0013) and distant metastases (P = 0.005). Age, gender, duration of symptoms,
      and physician delay, could not be shown to have any effect on survival. This
      study demonstrates that the aggressive nature of gastric cancer, particularly in
      certain minority ethnic groups, is the overriding prognostic feature.

PMID- 8256943
TI  - Factors influencing survival in advanced gastric cancer.
AB  - Even though the incidence of gastric carcinoma is decreasing, the prognosis
      remains poor. A review of 88 patients with advanced gastric cancer was evaluated
      by univariate and multivariate analysis to determine prognostic factors.
      Univariate analysis showed that both "curative" resection (P = 0.006) and
      adjuvant chemotherapy (P = 0.02) were important therapy variables. These factors
      were not independent when evaluated by multivariate analysis. However, when they
      were combined and re-evaluated by multivariate analysis, the combination of
      "curative" surgery and adjuvant chemotherapy significantly improved survival in
      advanced gastric cancer (P = 0.04).

PMID- 8256944
TI  - Subtotal splenectomy for Gaucher's disease: a follow-up study.
AB  - Three patients with Gaucher's disease who underwent partial splenectomy have been
      followed for 3, 7 3/4, and 8 1/2 years. All have had significant regrowth of the
      the splenic remnant and some recurrence of hypersplenism. A review of all
      previously reported cases also substantiates the recurrence of splenomegaly and
      hypersplenism. Among new options for the therapy of Gaucher's disease, enzyme
      replacement therapy (Ceredase) holds great promise for effective treatment.

PMID- 8256945
TI  - [Life-or-death emergencies in pediatrics: new approaches, new drugs].

PMID- 8256946
TI  - [Chronic encephalopathy in patients with sex-linked agammaglobulinemia].
AB  - The clinical and neuroradiological findings of two patients with X-linked
      agammaglobulinemia, who developed a chronic encephalopathy, are presented. The
      main neurological manifestations in both patients were: progressive spastic
      tetraparesis, cortico-subcortical type of dementia and seizures. No infectious
      agent was identified in either patient. A systematic review of the clinical
      findings of 37 patients reported in the literature with X-linked
      agammaglobulinemia and chronic encephalopathy allows the distinction of two
      subgroups of patients according to their form of presentation (acute or
      insidious). In each subgroup there are significant clinical differences. The
      clinical-neuroradiological similarities between this complication and the ones
      derived from the vertically transmitted form of the human immunodeficiency virus
      are pointed out. Finally, emphasis is made on the need for CSF viral cultures on
      patients with X-linked agammaglobulinemia as soon as a neurological complication
      is suspected.

PMID- 8256947
TI  - [Histological lesions and Helicobacter pylori colonization in children].
AB  - We have assessed the relationship between histologic findings and the
      Helicobacter pylori (HP) colonization in 115 patients (age: 9.8 +/- 3.5 years)
      with HP infection. Normal antral histology was found in 8.7% of the patients.
      Signs of histological activity were observed in 58.2% of the patients and
      glandular lesions in 3.5%. A significantly greater HP colonization was observed
      in patients with signs of histological activity (p < 0.001). A significant
      correlation was found between the HP colonization score and histological score
      (rs = 0.62) with a significant association between the degree of HP colonization
      and the histologic categories (p < 0.001).

PMID- 8256948
TI  - [A critical analysis of school screenings. The performance of each type of
      examination].
AB  - The results of a student screening program performed by the Primary Care Team of
      Gandia on 359 children (180 males and 179 females) that attended 1. EGB are
      presented. We reviewed the following: vision, hearing, dentition, somatometry,
      immunization, and urological and traumatological problems. Children with
      pathologies were referred to specialists to confirm the diagnosis. Of these
      children, 78% had some form of pathology. The most frequent system involved was
      hearing, followed by dentition and vision. The correlation of these results with
      those of the specialists was good (> 50%). The best results were obtained on
      vision screening results (100% correlation and 2/3 of the problems formerly
      detected). Twenty-four percent of the children had caries and this was not of
      major concern to the families. The worst results were obtained in auditive
      screening. Because the primary care examination model is not generalized, school
      screening is still a good method to detect previously undiagnosed pathologies in
      children.

PMID- 8256949
TI  - [Vitreous fluorophotometry and nocturnal GH secretion in young insulin-dependent
      diabetics treated with oral pirenzepine].
AB  - With the aim of finding a correlation between the blocking of G.H. secretion and
      the irregularities in the permeability of the hematoretinal barrier, we have
      studied the average nocturnal G.H. levels (NAGHL) and the vitreous penetration
      rate (VPR) in five young diabetic patients. These patients, 3 males and 2
      females, were between the ages of 12 and 17 years with a mean age of 16.0. They
      were studies both before and after receiving treatment for one month with an oral
      nocturnal dose of 0.6 mg/kg of pirenzepine (gastrozepin) and 1 mg/kg during the
      subsequent five months. We also tried to find a relationship between the VPR post
      treatment and the evolution time of their illness and with their BA1C. The most
      important results found in this study were: 1) the nocturnal oral pirenzepine
      modified the NAGHL in the study population (10.48 +/- 4.94 vs; 4.34 +/- 2.53
      ng/ml; p < 0.05). 2) Ingestion of the aforementioned drug did not affect the VPR
      (4.84 +/- 2.08 vs 4.53 +/- 2.54 x 10(-6)/min; p > 0.05). We have not found a
      relationship between the VPR after treatment with either the HBA1C levels or with
      the evolution time of the illness. Therefore, we conclude that the dose of oral
      pirenzepine used for 6 months, although it definitely decreases G.H. secretion,
      does not modify the permeability of the B.H.R. within this group of young
      diabetics. Hence, we can infer that the G.H. hypersecretion does not seem to have
      a relationship, at least exclusively, with the development of diabetic
      retinopathy.

PMID- 8256950
TI  - [Lactose-free formula versus adapted formula in acute infantile diarrhea].
AB  - We have studied a population of 60 children with acute diarrhea. In order to
      evaluate the benefit of lactose suppression from the diet on the clinical course
      of the disease, these children were randomly assigned to either the control group
      or the experimental group. No differences were found in respects to the duration
      of the illness (lactose containing formula 4.8 +/- 2 days vs lactose free formula
      4.4 +/- 3.1 days). Similarly, body weight change did not change significantly
      (12.5 +/- 235.8 gr vs 55.9 +/- 238.0 gr, t-test non-significant). Children fed
      with the lactose free diet voided less frequently than did children in the
      control group (12.8 +/- 10.5 vs 19.8 +/- 9.5 times; p < 0.01). This difference
      disappeared when only invasive diarrheas were considered (26.6 +/- 12 vs 21.5 +/-
      9.5 voidings; t-test nonsignificant). Finally, only 2 of the 32 cases fed with
      lactose containing formula showed clinical intolerance to lactose. Therefore, we
      conclude that in patients with mild-to-moderate acute diarrhea, the resumption of
      feeding should be undertaken with the same formula that they were previously fed,
      restricting the use of lactose free formulas to selected cases and to those
      children in whom a standard milk made symptoms reappear.

PMID- 8256951
TI  - [Pediatric fiber bronchoscopy. Apropos 55 children examined].
AB  - We present our experience with 55 children in which we performed flexible
      fiberoptic bronchoscopy (FFB) using an Olympus BF3C20 instrument and by using
      sedation and local anaesthesia or laryngeal mask airway. Indications for
      performing this procedure were stridor, opportunist or recurrent pneumonia,
      persistent atelectasis, a suspected foreign body, confirmation of endobronchial
      tuberculosis and evaluation of tracheostomy. In 70% of the cases, the diagnosis
      was made by the FFB and 14 cases were normal. One child with severe hypoxia
      presented respiratory arrest and need intubation. Our results suggest that FFB is
      safe, has advantages over rigid bronchoscopy, avoids general anaesthetic and with
      laryngeal mask airway is possible to perform in patients of every age.

PMID- 8256952
TI  - [Tuberculosis: a present reality].
AB  - Some of the causes which may account for the high incidence of tuberculosis in
      children in our environment have been analyzed. Twelve cases of tuberculosis have
      been included in the study (seven pulmonary cases, two cases of bone
      tuberculosis, one nodosum erythema and one miliary tuberculosis in an HIV
      positive patient). Based upon our series, we report on some mistakes in the
      diagnosis, specific treatment and chemoprophylaxis. We have tried to briefly
      outline the steps which should be taken to overcome these problems.

PMID- 8256953
TI  - [Enuresis and encopresis: their relationship].
AB  - The incidence and types of enuresis in 113 encopretic children were studied. The
      sex ratio was 5.17 males to every 1 female. Half of the patients were enuretics
      (50.44%). Of these, 78.9% were primary and secondary enuretics. No primary
      encopretic manifested secondary enuresis. The ratio of primary to secondary
      enuresis (3.75:1) in children with encopresis was much lower than in the
      population of enuretics. Of the enuretic encopretics, 40.34% had mixed or diurnal
      bladder incontinence. The results emphasize the role of peripheral dysfunctions
      and constipation-encopresis in the etiology of some enuresis. The therapeutic
      implications of these findings are also discussed.

PMID- 8256954
TI  - [Bronchiectasis in early childhood. Its surgical treatment].
AB  - We discuss the measures used, including physical examination, radiology,
      scintigraphy, T.A.C. and bronchography, to diagnoses 34 patients with
      bronchiectasis. In addition, the treatment used up until the time where the
      decision to perform surgery is also presented. Ten patients were submitted to
      surgical intervention and their operations, as well as the effected lobes, are
      described. The guidelines for surgical preparation, surgical difficulties
      encountered, postoperative care and the results of the surgeries are all
      discussed. Due to the age of some of these patients, obvious difficulties
      prevented functional testing. In those patients in whom it was possible, no loss
      in respiratory capacity has been observed.

PMID- 8256956
TI  - [Consensus conference. The clinical indications and risks with fresh frozen
      plasma].

PMID- 8256955
TI  - [Symptomatic Chiari type-II malformation in the neonatal period: a review of 4
      cases].
AB  - Four newborn patients with symptomatic Chiari II malformations were studied
      retrospectively. Clinical manifestations and surgical results are presented. All
      of these patients had hydrocephalus, which was symptomatic in two patients from
      the first day of life. Three of them had bradycardia and apnea spells. Two
      patients had lower cranial nerve palsies. Cranial sonography was the first
      neuroimaging procedure used and it played an important role during the follow-up
      period, especially for the study of the hydrocephalus. Two newborns could be
      studied with Magnetic Resonance Imaging (MRI). It defined the level of the decent
      of the fossa posterior structures and the associated malformations. All of the
      patients were treated with surgical repair of the spinal dysraphism, ventricular
      shunt and decompressive surgery. Two patients died before the age of three
      months. Two other patients showed better evolution after their two year and four
      year check-ups, respectively. Bradycardia and apnea spells are features that
      worsen the prognosis as compared with other manifestations.

PMID- 8256957
TI  - [Invasive angiology in acute arterial pathology in a critically ill newborn
      infant].

PMID- 8256958
TI  - [Children of a mother with a kidney transplant. Apropos 4 cases. A bibliographic
      review].

PMID- 8256959
TI  - [Persistent neutropenia in congenital cytomegalovirus infection. A case report].

PMID- 8256960
TI  - [Congenital toxoplasmosis in a newborn infant with AIDS].

PMID- 8256961
TI  - [Neonatal hyperthyroidism].

PMID- 8256962
TI  - [Acute encephalopathy caused by Shigella sonnei].

PMID- 8256963
TI  - [Acute bacterial tracheobronchitis: a pathology forgotten in the diagnosis of
      severe croup].

PMID- 8256964
TI  - [Secondary renal amyloidosis in childhood. A review apropos 2 cases].

PMID- 8256965
TI  - [Otitis media due to Vibrio alginolyticus: the risks of the Mediterranean Sea].

PMID- 8256966
TI  - [Fetal surgery in 1992].

PMID- 8256967
TI  - [Accidental dextromethorphan poisoning].

PMID- 8256968
TI  - The effect of comorbidity on 3-year survival of women with primary breast cancer.
AB  - OBJECTIVE: To determine the effect of comorbidity and stage of disease on 3-year
      survival in women with primary breast cancer. DESIGN: Longitudinal, observational
      study. SETTING: Metropolitan Detroit. PATIENTS: 936 women ages 40 to 84 years.
      MEASUREMENTS: Data on stage of breast cancer, treatment type, and comorbidity
      were obtained from Metropolitan Detroit Cancer Surveillance System (MDCSS) files
      and medical records. Personal interviews were the source of information on social
      and behavioral factors. Vital status and cause of death were obtained from MDCSS
      files. RESULTS: Patients who had 3 or more of 7 selected comorbid conditions had
      a 20-fold higher rate of mortality from causes other than breast cancer and a 4
      fold higher rate of all-cause mortality when compared with patients who had no
      comorbid conditions. The effects of comorbidity were independent of age, disease
      stage, tumor size, histologic type, type of treatment, race, and social and
      behavioral factors. Moreover, women with severe comorbid conditions had uniformly
      higher mortality rates, and early diagnosis in these women conferred no survival
      advantage. CONCLUSION: Comorbidity in patients with breast cancer appears to be a
      strong predictor of 3-year survival, independent of the effects of breast cancer
      stage. This finding suggest that trials assessing the efficacy of screening
      should routinely include measures of comorbidity.

PMID- 8256969
TI  - Effects of coronary angioplasty, coronary bypass surgery, and medical therapy on
      employment in patients with coronary artery disease. A prospective comparison
      study.
AB  - OBJECTIVE: To compare return-to-work rates after coronary angioplasty, coronary
      bypass surgery, and medical therapy in patients with coronary disease. DESIGN:
      Prospective cohort study. SETTING: Tertiary care referral center. PATIENTS:
      Between March 1986 and June 1990, we enrolled 1252 patients who were younger than
      65 years, who had not had previous coronary revascularization, and who were
      employed. All patients were followed for 1 year. MAIN OUTCOME MEASURE: One-year
      employment status. RESULTS: After 1 year, 84% of patients who had coronary
      angioplasty were still working compared with 79% of patients who had bypass
      surgery and with 76% of patients who received medicine. After adjusting for the
      more favorable baseline characteristics of patients who had angioplasty (less
      severe coronary artery disease, better left ventricular function, and less
      functional impairment), however, no significant differences were noted in 1-year
      employment rates among the three groups. These adjusted 1-year return-to-work
      rates were 84% for angioplasty, 80% for surgery, and 79% for medicine (P > 0.05).
      In a random subset of 72 patients, 23 patients who had angioplasty returned to
      work after a median of 18 days (mean, 27 days) compared with 54 days (mean, 67
      days) for 24 patients having bypass surgery and with 14 days (mean, 45 days) for
      25 patients receiving medicine (P = 0.002). CONCLUSIONS: Patients who had
      coronary angioplasty were able to return to work earlier than those who had
      bypass surgery, but by 1 year no significant difference was noted in employment
      rates. Neither revascularization strategy improved employment rates when compared
      with initial treatment using medical therapy.

PMID- 8256970
TI  - Clinical and epidemiologic characteristics of Mycobacterium haemophilum, an
      emerging pathogen in immunocompromised patients.
AB  - OBJECTIVE: To describe 13 infections caused by Mycobacterium haemophilum. DESIGN:
      Identification of patients by microbiologic record review, followed by medical
      record review and a case-control study. SETTING: Seven metropolitan hospitals in
      New York. PATIENTS: All patients with M. haemophilum infections diagnosed between
      January 1989 and September 1991 and followed through September 1992. Surviving
      patients were enrolled in the case-control study. RESULTS: Infection with M.
      haemophilum causes disseminated cutaneous lesions, bacteremia, and diseases of
      the bones, joints, lymphatics, and the lungs. Improper culture techniques may
      delay laboratory diagnosis, and isolates may be identified incorrectly as other
      mycobacterial species. Persons with profound deficits in cell-mediated immunity
      have an increased risk for infection. These include persons with human
      immunodeficiency virus infection or lymphoma and those receiving medication to
      treat immunosuppression after organ transplant. Various antimycobacterial
      regimens have been used with apparent success to treat M. haemophilum infection.
      However, standards for defining antimicrobial susceptibility to the organism do
      not exist. CONCLUSIONS: Clinicians should consider this pathogen when evaluating
      an immunocompromised patient with cutaneous ulcerating lesions, joint effusions,
      or osteomyelitis. Microbiologists must be familiar with the fastidious growth
      requirements of this organism and screen appropriate specimens for mycobacteria
      using an acid-fast stain. If acid-fast bacilli are seen, M. haemophilum should be
      considered as the infecting organism as well as other mycobacteria, and
      appropriate media and incubation conditions should be used.

PMID- 8256971
TI  - Health of family members caring for elderly persons with dementia. A longitudinal
      study.
AB  - OBJECTIVE: To estimate the change in depression and physical symptoms during a 1
      year period in a group of caregivers for elderly persons with dementia and in a
      group of comparison participants. DESIGN: Cohort study with a comparison group.
      SETTING: Outpatient geriatric assessment unit and ophthalmology service in an
      acute care hospital. PARTICIPANTS: 218 close family members of a consecutive
      sample of patients with dementia and patients having cataract surgery were
      interviewed to obtain a baseline assessment. Of these, 86 caregivers (family
      members of patients with dementia) and 95 comparison participants (family members
      of patients with cataracts) were interviewed again approximately 1 year later.
      MAIN OUTCOME MEASURES: Center for Epidemiologic Studies depression scale and Aday
      and Andersen's 24-item physical symptom checklist. RESULTS: For the Center for
      Epidemiologic Studies depression score, the difference between caregivers and
      comparison participants with respect to change during the 1-year study period was
      2.1 (95% CI, 1.0 to 5.2); for physical symptoms, the difference was 0.4 (CI, -0.3
      to 1.1). A higher level of behavioral disturbance in the patients with dementia
      at time 1 and institutionalization of the patient between time 1 and time 2 were
      predictive of worsening caregiver depression and physical symptoms during the
      study period. The magnitude and direction of changes in caregiver health varied
      considerably. CONCLUSIONS: Overall mean changes in depression and physical
      symptoms during 1 year were small. The observed variability in the individual
      response to the caregiving situation suggests that future research should focus
      on the identification of salient prognostic factors.

PMID- 8256972
TI  - Liver transplantation as a treatment for familial amyloidotic polyneuropathy.

PMID- 8256973
TI  - Effects of computer-based clinical decision support systems on clinician
      performance and patient outcome. A critical appraisal of research.
AB  - OBJECTIVE: To review the evidence from controlled trials of the effects of
      computer-based clinical decision support systems (CDSSs) on clinician performance
      and patient outcomes. DATA SOURCES: The literature in the MEDLARS, EMBASE,
      SCISEARCH, and INSPEC databases was searched from 1974 to the present. Conference
      proceedings and reference lists of relevant articles were reviewed. Evaluators of
      CDSSs were asked to identify additional studies. STUDY SELECTION: 793 citations
      were examined, and 28 controlled trials that met predefined criteria were
      reviewed in detail. DATA EXTRACTION: Study quality was assessed, and data on
      setting, clinicians and patients, method of allocation, computer system, and
      outcomes were abstracted and verified using a structured form. Separate summaries
      were prepared for physician and patient outcomes. Within each of these
      categories, studies were classified further according to the primary purpose of
      the CDSS: drug dose determination, diagnosis, or quality assurance. RESULTS:
      Three of 4 studies of computer-assisted dosing, 1 of 5 studies of computer-aided
      diagnosis, 4 of 6 studies of preventive care reminder systems, and 7 of 9 studies
      of computer-aided quality assurance for active medical care that assessed
      clinician performance showed improvements in clinician performance using a CDSS.
      Three of 10 studies that assessed patient outcomes reported significant
      improvements. CONCLUSIONS: Strong evidence suggests that some CDSSs can improve
      physician performance. Additional well-designed studies are needed to assess
      their effects and cost-effectiveness, especially on patient outcomes.

PMID- 8256974
TI  - Recommended guidelines for the management of autologous and allogeneic bone
      marrow transplantation. A report from the Eastern Cooperative Oncology Group
      (ECOG)
AB  - OBJECTIVE: To define the basic state-of-the-art medical care of the patients
      after bone marrow transplantation as practiced by the Eastern Cooperative
      Oncology Group. DATA IDENTIFICATION: Studies examining the role of bone marrow
      transplantation in the care of neoplastic disorders identified using computer and
      bibliographic searches. STUDY SELECTION: More than 500 articles, book chapters,
      and abstracts from meetings, covering all therapeutic and diagnostic aspects of
      the patient having bone marrow transplantation were critically reviewed;
      information from over 200 publications is included. RESULTS OF DATA ANALYSIS:
      Enormous progress has been made in understanding the biology, therapy, and
      prophylaxis strategies of bone marrow transplantation and in extending the range
      of potential marrow donors to include unrelated persons. Dramatic advances have
      occurred in the prevention of serious infection, including cytomegalovirus
      infection, formerly a cause of a high rate of mortality. The advent of newer
      combination, high-dose chemotherapy regimens and advances in cryopreservation and
      in vitro marrow purging techniques have led to increased use and greater efficacy
      of autologous transplantation. Recent advances using recombinant hematopoietic
      growth factors and autologous peripheral stem cells are likely to reduce
      morbidity and mortality and significantly shorten the length of hospitalization
      and the cost of bone marrow transplantation. CONCLUSIONS: Bone marrow
      transplantation now is a common procedure done throughout the world. Cooperative
      groups have assumed a major role in conducting clinical trials. A standardized
      approach defining basic standards of care will assure uniformity of management,
      better interpretation of data, and continued progress in the care of the patient
      who has had a bone marrow transplantation. Basic research and clinical trials are
      ongoing to define better methods for the treatment and prevention of graft-versus
      host disease and hepatic veno-occlusive disease.

PMID- 8256975
TI  - He's still alive!

PMID- 8256976
TI  - Antisense oligonucleotide therapies: are they the "magic bullets"?

PMID- 8256977
TI  - The injured worker and the internist.

PMID- 8256978
TI  - Assessing the cure of the Zollinger-Ellison syndrome after gastrinoma resection.

PMID- 8256979
TI  - Urea excretion rate as a contributor to trimethoprim-induced hyperkalemia.

PMID- 8256980
TI  - Halofantrine treatment of Plasmodium falciparum malaria.

PMID- 8256981
TI  - Reversed form of differential collapsing pulses.

PMID- 8256982
TI  - Hypothyroidism and primary pulmonary hypertension.

PMID- 8256983
TI  - CD4+ lymphocytopenia in systemic lupus erythematosus.

PMID- 8256984
TI  - Monitoring heparin therapy.

PMID- 8256985
TI  - Monitoring heparin therapy.

PMID- 8256986
TI  - Individualizing therapy.

PMID- 8256987
TI  - The course of non-A, non-B hepatitis unrelated to transfusion.

PMID- 8256988
TI  - Calcium supplementation with and without hormone replacement therapy to prevent
      postmenopausal bone loss.
AB  - OBJECTIVE: To determine whether augmentation of dietary calcium is effective in
      the prevention of early postmenopausal bone loss. DESIGN: Three-arm, placebo
      controlled, randomized parallel trial. The study duration was 2.9 +/- 1.1 (SD)
      years. SETTING: General community. PARTICIPANTS: 118 healthy, white women 3 to 6
      years after spontaneous menopause, recruited by community announcement.
      INTERVENTIONS: Random allocation to daily intake of 1700 mg of calcium (calcium
      carbonate given in divided doses with meals); placebo; or conjugated equine
      estrogens (0.625 mg; days 1 to 25), progesterone (10 mg; days 16 to 25), and 1700
      mg of elemental calcium daily. Each participant  received 400 IU of vitamin D
      daily. MAIN OUTCOME MEASURES: Total body calcium measured by delayed gamma
      neutron activation  analysis and whole-body counting; bone mineral density of the
      spine, femur, and radius measured by photon absorptiometry. RESULTS: Bone mineral
      density declined in the placebo group for the lumbar spine (-2.1%/y; 95% Cl, -3.3
      to -0.9), femoral neck (-2.0%/y; Cl, -2.6 to -1.2), trochanter (-1.6%/y; Cl, -2.4
      to -0.8), Ward triangle (-2.7%/y; Cl, -3.7 to -1.7), and total body calcium (
      2.0%/y; Cl, -2.2 to -1.8). Rates of change were intermediate for calcium
      augmentation compared with placebo and estrogen-progesterone-calcium but
      statistically significant compared with placebo for total body calcium (-0.5%/y;
      Cl, -0.9 to -0.1; P = 0.006) and the femoral neck (-0.8%/y; Cl, -1.4 to -0.2; P =
      0.03). CONCLUSIONS: Although less effective than estrogen-progesterone-calcium,
      calcium augmentation alone significantly retards bone loss from the femoral neck
      and improves calcium balance in recently postmenopausal women. Dietary calcium
      augmentation should be recommended as a strategic option in helping to prevent
      early postmenopausal bone loss.

PMID- 8256989
TI  - [Special proceedings of a law project concerning "the accusation of dementia":
      case of Joseph Firmin nicknamed Retif (1794-1799)].
AB  - The study of a long neglected bill about the accused in a state of mental
      alienation debated by the legislative assembly of the french Directoire (1794
      1799) following a ruling in the Joseph Firmin case. The parliamentary debate on
      this bill is of real historical interest, since for the first time after the
      french Revolution its thirteen sections propose to institute special proceedings
      in case of mental alienation, midway between the penal code of 1791, which does
      not contain such provisions and the napoleonic code of 1810, it opens the way for
      the wellknown section 64 of this later code which sets the rules for over a
      hundred and eighty years.

PMID- 8256990
TI  - [The annals and Medical-psychological Society. Their historical dynamics].

PMID- 8256991
TI  - [Jules Baillarger (1809-1891), founder of The Medical-Psychological Annals].

PMID- 8256992
TI  - [150 years of The Medical-psychological Annals].

PMID- 8256993
TI  - [The Medical-psychological Annals and French psychiatric literature 150 years
      later. Bilan 1992].

PMID- 8256994
TI  - [The place of Toulouse in the history of French psychiatry].

PMID- 8256995
TI  - [The place of French psychiatry in European psychiatry].

PMID- 8256996
TI  - [The creation of a judiciary pavilion in connection with difficult diseases of
      Cadillac. The first undertaking in French psychiatry].

PMID- 8256997
TI  - [Historical epistemology and history of psychiatry].

PMID- 8256998
TI  - [Epistemological monism in reference to scientific psychiatry].

PMID- 8256999
TI  - [Adam Cygielstrejch's two prophetic texts, published in The Medical-
      psychological annals in 1912, on "mental disorders of war during the Russian
      Japanese war in 1904-1905].

PMID- 8257000
TI  - [History of the borderline concept].

PMID- 8257001
TI  - [Anorexia and lycanthropy ++: grandiosity and fall].

PMID- 8257002
TI  - [On the family placement at the service of family therapy: 150 years of Medical
      psychological annals].
AB  - The historic of families colony (Geel in Belgium) brought a great debate in the
      "Annales Medico-Psychologiques", 150 years ago. The controversy stay very actual
      between hospitalocentrisme orientation and deinstitutionalization movement. The
      economic motivations influence very often on the final orientation of the mental
      health system.

PMID- 8257003
TI  - [Against the death penalty, an abolitionist in the Medical-psychological
      Society:Felix Voisin].

PMID- 8257004
TI  - Corticotropin-releasing factor-binding protein. A putative peripheral and central
      modulator of the CRF family of neuropeptides.

PMID- 8257005
TI  - Neuropeptides, the stress response, and the hypothalamo-pituitary-gonadal axis in
      the female rhesus monkey.
AB  - In conclusion, we have demonstrated that in the primate increased activity of the
      immune system and the consequent IL-1 release result in the activation of
      neuropeptides of the adrenal axis, mainly CRF and AVP. These neuropeptides,
      through a direct effect on the GnRH pulse generator or indirectly through the
      hypothalamic endogenous opioid peptides, inhibit the GnRH pulse generator. Some
      of the POMC derivatives, such as alpha-MSH, may antagonize these effects. The
      consequential decrease in GnRH pulse frequency results in an acute decrease in LH
      and FSH secretion. This decrease in gonadotropin release may explain the
      deleterious effects of stress on the menstrual cycle. However, an acute decrease
      in gonadotropins following activation of the adrenal axis is not observed in the
      presence of estradiol. Thus, during the menstrual cycle, a relative protection
      against the deleterious effects of acute stress may exist. How potent this
      protective mechanism is against repetitive stress is not known.

PMID- 8257006
TI  - Central mechanisms and sites of action involved in the inhibitory effects of CRF
      and cytokines on LHRH neuronal activity.

PMID- 8257007
TI  - The role of limbic and hypothalamic corticotropin-releasing factor in behavioral
      responses to stress.
AB  - CRF in the central nervous system appears to have activating properties on
      behavior and to coordinate behavioral responses to stress. These behavioral
      effects of CRF appear to be independent of the pituitary-adrenal axis and can be
      reversed by a CRF antagonist, alpha-helical CRF9-41. The CRF antagonist reverses
      not only decreases in behavior associated with stress, but also increases in
      behavior associated with stress, thus suggesting that the role of CRF is stress
      dependent and not intrinsic to a given behavioral response. Further,
      microinjection of alpha-helical CRF9-41 and immunotargeting of CRF neurons in
      separate brain compartments reveal a link between the anatomical sites that
      contain CRF and the nature of the behavioral response to stress that can be
      modified by suppression of endogenous CRF activity therein. Hence, consistent
      with the dual role of other hypothalamic-releasing factors in integrating
      hormonal and neural mechanisms by acting both as secretagogues for anterior
      pituitary hormones and as extrapituitary peptide neurotransmitters, CRF may
      coordinate coping responses to stress at several bodily levels (Fig. 6).
      Moreover, dysfunction in such a fundamental homeostatic system may be the key to
      a variety of pathophysiological conditions including mental disorders.

PMID- 8257008
TI  - Involvement of corticotropin-releasing factor in the control of food intake and
      energy expenditure.

PMID- 8257009
TI  - Role of cytokines in infection-induced stress.

PMID- 8257010
TI  - Stress-induced immune suppression. Role of the autonomic nervous system.
AB  - Experimental data together with clinical studies have generated information about
      the association between sympathetic nervous system activity and immunity as
      measured by in vitro correlates of cellular immune function. In addition, studies
      on the in vivo role of central CRF in coordinating sympathetic outflow and
      modulating immune function have provided an opportunity to examine central
      mechanisms important in the link between brain, behavior, and immune function.
      Finally, use of CRF as a neuropeptide probe will likely continue to give
      information about the central mechanisms relevant to the abnormal regulation of
      sympathetic nervous activity and immune function in stress and possibly in aging.

PMID- 8257011
TI  - CRF and related peptides as anti-inflammatory agonists.
AB  - The permeability of endothelial surfaces increases in response to injury. We have
      shown that vascular leakage in experimental models of tissue injury can be
      inhibited by CRF and by a novel class of peptides that we call mystixins. Binding
      sites for iodinated-Tyro-CRF have been revealed in mucous membranes, and
      immunoreactive CRF-like materials have been found in inflamed tissues. Perhaps
      the breakdown of cytoskeletal intermediate filaments after insult generates or
      exposes peptide domains similar to mystixins. Endogenous CRF-like or mystixin
      like peptides, if activated or released locally in injured tissues, may function
      as agonists to counteract the immediate inflammatory response. If this is so, the
      peripheral actions of these peptides add a new dimension to the idea that CRF and
      related substances organize and regulate an organism's response to stress.

PMID- 8257012
TI  - "Restraint ulcer" as a model of stress-induced gastric lesion. A historical note.

PMID- 8257013
TI  - Role of CRF in stress-related alterations of gastric and colonic motor function.
AB  - Major advances have been made in the understanding of the pathophysiology of
      stress-related alteration of gut function. A wealth of information indicates that
      CRF is involved in the central mechanisms by which stress inhibits gastric
      emptying while stimulating colonic motor function. CRF acts in the PVN to trigger
      both the inhibition of gastric emptying and the stimulation of colonic motor
      function in response to stress, in addition to previously established endocrine
      and behavioral responses. Preliminary evidence exists that CRF acts in the locus
      coeruleus to induce a selective stimulation of colonic transit without
      influencing gastric emptying. The central actions of CRF to alter gastric and
      colonic motor function are conveyed by autonomic pathways and are unrelated to
      the associated stimulation of pituitary hormone secretion. The demonstration that
      central CRF plays a role in mediating gastric stasis resulting from surgery,
      peritonitis or high levels of central interleukin-1 provides new insight into the
      mechanisms involved in gastric ileus induced postoperatively or by infectious
      disease. Likewise, the demonstration that CRF in the PVN and locus coeruleus
      induce the anxiogenic and colonic motor responses to stress and that colonic
      distention activates neurons in the locus coeruleus opens new avenues for the
      understanding of the pathogenesis of a subset of IBS patients with colonic
      hypersensitivity associated with psychopathological disturbance and diarrhea
      predominant symptoms.

PMID- 8257014
TI  - Interaction between neuropeptide Y and sigma ligands in the modulation of CRF and
      stress-induced alteration of gastrointestinal function.

PMID- 8257015
TI  - Regulation of small intestinal and pancreaticobiliary functions by CRF.

PMID- 8257016
TI  - Immunopathology of ulcer disease.

PMID- 8257017
TI  - Stress and behavior in domestic animals. Temperament as a predisposing factor to
      stereotypies.

PMID- 8257018
TI  - Stress and reproduction in domestic animals.

PMID- 8257020
TI  - Stress and disease in domestic animals.

PMID- 8257019
TI  - CRF mRNA in normal and stress conditions.

PMID- 8257021
TI  - Phenotypic plasticity of CRF neurons during stress.

PMID- 8257022
TI  - Amygdaloid CRF pathways. Role in autonomic, neuroendocrine, and behavioral
      responses to stress.
AB  - The results of numerous studies have provided compelling evidence that CRF plays
      an important function in the amygdala. Stimulation of the amygdala produces
      physiological changes similar those observed after central injections of CRF.
      Central injections of CRF activate neurons in the amygdala as measured by
      increases in c-fos protein expression. Destruction of cells or injections of CRF
      antagonist in the amygdala can attenuate some of the central effects of CRF. The
      amygdala is the origin of major CRF-containing pathways in the brain. Amygdaloid
      CRF neurons project to widespread regions of the basal forebrain and brain stem.
      These amygdaloid pathways mainly arise from the central amygdaloid nucleus where
      there are a large number of CRF immunoreactive neuronal perikarya. Glucocorticoid
      and CRF-binding protein are located in cells of the central amygdaloid nucleus.
      CRF neurons in the central nucleus send their axons to the bed nucleus of the
      stria terminalis, lateral hypothalamus, midbrain central gray, raphe nuclei,
      parabrachial region, and the nucleus of the solitary tract. Tract tracing studies
      have suggested that amygdaloid CRF neurons also innervate CRF neurons in some of
      these regions and, furthermore, that CRF neurons in some of these areas project
      back to the CRF neurons in the amygdala. Thus, the amygdala is part of a network
      of brain nuclei interconnected by CRF pathways. In addition, amygdaloid CRF
      neurons may project directly to dopaminergic, noradrenergic, and serotonergic
      neurons, which have widespread projections throughout the neuroaxis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257023
TI  - The psychoendocrinology of stress.

PMID- 8257024
TI  - Individual differences in the hypothalamic-pituitary-adrenal stress response and
      the hypothalamic CRF system.

PMID- 8257025
TI  - Neuroendocrine effects of prenatal alcohol exposure.

PMID- 8257026
TI  - Corticotropin-releasing factor and interleukin-1 receptors in the brain-endocrine
      immune axis. Role in stress response and infection.
AB  - CRF and IL-1 receptors were identified, characterized, and localized in brain,
      endocrine, and immune tissues. CRF receptors with comparable kinetic and
      pharmacological characteristics were localized in the anterior and intermediate
      lobes of the pituitary, in brain areas involved in mediating stress responses,
      and in the macrophage-enriched marginal zones of the spleen. The discrete
      localization of IL-1 receptors in neurons of the hippocampus provides further
      support for the role of IL-1 as a neurotransmitter/neuromodulator/growth factor
      in the CNS. The neuroendocrine effects of IL-1 may be mediated through actions of
      the cytokine in brain. However, given the high densities of IL-1 receptors in the
      anterior pituitary and testis, direct effects of the cytokine at the pituitary or
      gonadal levels seem highly likely. Overall, these data support a role for IL-1
      and CRF in coordinating and integrating the brain-endocrine-immune responses to
      physiological, pharmacological, and pathological stimuli.

PMID- 8257027
TI  - Effect of peripheral and central cytokines on the hypothalamic-pituitary-adrenal
      axis of the rat.

PMID- 8257028
TI  - [Repartition of mankind on the earth and role of cutaneous melanization].

PMID- 8257029
TI  - [Familial form of rheumatoid nodulosis].
AB  - We report a familial form of rheumatoid nodulosis where the early lesions
      appeared in the first years of life in a young man and his son. The numerous
      papular and nodular skin lesions disclosed an ulcerative evolution leaving
      atrophic scars mainly near the limbs' joints. In both patients the evolution was
      characterized by the late onset of polyarthralgias and of a non-destructive
      seronegative polyarthritis; intra-osseous lesions were present in the metatarsal
      bones in the father. Rheumatoid nodulosis is a rare disease, sometimes considered
      as a benign variant of rheumatoid arthritis without destructive joint
      involvement. A serum rheumatoid factor is inconstantly present and the intra
      osseous geodes have been shown to be rheumatoid nodules exhibiting the same
      histological structures of palisading granulomas as the subcutaneous nodules. The
      main symptom of the disease is the occurrence of multiple nodules followed by the
      delayed onset of a polyarthritis with a benign course without systemic
      involvement.

PMID- 8257030
TI  - [Granuloma annulare and carpal tunnel syndrome].
AB  - This is a report of 4 cases of cutaneous granuloma annulare associated with
      carpal-tunnel syndrome. Biopsies of skin lesions and carpal flexor synovialis
      both show a picture of palisading granuloma consistent with granuloma annulare.

PMID- 8257031
TI  - [Sturge-Weber-Krabbe syndrome. A severe form in a monozygote female twin].
AB  - We report a severe case of Sturge-Weber syndrome in one of two monozygotic twins.
      This syndrome included a facial portwine stain over the trigeminal ophthalmic V1
      area, and ipsilateral vascular anomalies of the eye and of the pia mater. CT
      scans and MRI were very informative. The cerebral regional blood flow, studied
      with SPECT, showed a paradoxically high rate.

PMID- 8257032
TI  - [Cutaneous ciliated cyst of the scapular area].
AB  - We report a case of ciliated cutaneous cyst located on the dorsal side of the
      right shoulder in a 22-years old woman. The anatomoclinical features of this rare
      variety of cyst are described and compared with those of the 17 published cases.
      The differential diagnosis with other glandular cysts is presented. The mullerian
      duct origin of ciliated cutaneous cysts is controverted, and the starting point
      of this lesion remains mysterious.

PMID- 8257033
TI  - [Type IV Ehlers-Danlos syndrome disclosed by acute obstructive renal
      insufficiency].
AB  - A 64 year-old man was admitted for congestive heart failure induced by an acute
      renal failure due to obstruction. Retroperitoneal periaortic-aneurysmal fibrosis
      was the etiology of the obstruction. Type IV Ehlers-Danlos syndrome was diagnosed
      based upon clinical and histological cutaneous signs.

PMID- 8257034
TI  - [Pseudoxanthoma elasticum and pregnancy].
AB  - We report the case of a pregnant woman suffering from pseudoxanthoma elasticum
      with typical cutaneous manifestations, arteritis of the lower limbs and angioid
      striae. The course of pregnancy was marked by transient inflection of the foetal
      growth curve with return to normal after a few weeks of rest in hospital.
      Delivery was effected by caesarean section in the 35th week of amenorrhoea; the
      placenta contained numerous calcifications. Two years after pregnancy, our
      patient experienced aggravation of skin lesions, but the arteritis and the ocular
      involvement remained unchanged. These "at risk" pregnancies must be closely
      monitored.

PMID- 8257035
TI  - [High predictive value of straightened hair for HIV infection in the adult
      population of Central Africa].

PMID- 8257036
TI  - [A case for diagnosis: white sponge nevus].

PMID- 8257037
TI  - [Protease inhibitors deficiencies in dermatology].

PMID- 8257038
TI  - [Treatment of squamous cell carcinoma of the penis by surgery and brachytherapy].

PMID- 8257039
TI  - [Question of the month: Behcet disease and contraception].

PMID- 8257040
TI  - [Surgical research in France].

PMID- 8257041
TI  - [Celioscopic surgery and law about the protection of persons in biomedical
      research].

PMID- 8257042
TI  - [Pediatric liver transplantation and related live donor. Technical and ethical
      considerations].
AB  - With improved results of liver transplantation, the number of candidates is
      increasing. However the scarcity of suitable grafts from cadaveric donors remains
      a limitation. In spite of the use of full size or reduced size grafts or partial
      grafts from split livers, some children still die while waiting for liver
      transplantation. We describe a successful orthotopic liver transplantation in a
      10 months old female using the left lateral lobe (segments II and III) from her
      27 years old father. The child suffered from biliary atresia, her condition was
      deteriorating with intractable ascites and increasing jaundice. The father asked
      us to give a part of his own liver to his daughter. The concept of this
      innovative therapy had already been submitted to a research-ethics consultation
      which gave us favorable conclusions. After careful donor evaluation, the left
      lateral lobe was harvested on July 22, 1992, including the left hepatic artery,
      left portal vein and left hepatic vein; hepatic artery for segment IV, which
      arose from the right structures, was preserved, The graft was immediately
      transplanted orthotopically after recipient total hepatectomy with inferior vena
      cava preservation. Cold ischemia time was 1 hour and 45 minutes,
      revascularization of the graft was homogeneous from the very beginning and its
      early function was excellent. Thirteen days after the operation, the donor was
      discharged in good condition. The child was reoperated at day 9 for a small
      biliary leak originating from the cut surface of the liver. After resolution of
      an episode of rejection and an intra-abdominal abscess, the child was discharged
      in good health with normal liver function 1 month post-transplant.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257043
TI  - [Risk factors of hepatectomies: results of a multivariate study. Apropos of 113
      cases].
AB  - 113 consecutive elective liver resections were performed in 107 patients over a
      period of 8 and half years. The indication was a malignant tumor in 75.2% of
      cases and a benign lesion in 24.8%. The remnant liver was pathologic in 22.1% of
      cases (16 steatosis, 8 cirrhosis and 1 fibrosis). The extent of liver resection
      was major (> or = 3 segments according to Couinaud classification) in 60 cases
      and minor in 45 cases. No intraoperative mortality occurred. Hospital mortality
      was 4.4%. Major complications, including death, occurred in 36.3% of cases
      (41/113). Statistical analysis of various risk factors was performed, regarding
      age, type of liver disease, cholestasis, surgical approach, extent of resection,
      type of hepatic vascular clamping, liver ischemia, quality of the remnant liver,
      intraoperative hemorrhage and length of the procedure. Multivariate analysis
      demonstrated three major statistically significant risk factors: pre operative
      cholestasis (r = 0.373; p = 0.0012), extent of liver resection (r = 0.377; p =
      0.0011), and intra operative blood transfusion (r = 0.364; p < 0.008) with a
      global correlation coefficient of 0.582 (p < 0.0001). These results should lead
      to better surgical selection for liver resection and reduced morbidity and
      mortality.

PMID- 8257044
TI  - [Lithiasis of the common bile duct (CBD) at the time of laparoscopic surgery.
      What strategy to follow?].
AB  - The best treatment for symptomatic or complicated gallstones is laparoscopic
      cholecystectomy, now performed in all countries throughout the world. Today, the
      new problem is how to treat common bile duct stones discovered during
      laparoscopic cholecystectomy. Between traditional "open surgery" and "exclusive
      laparoscopy" only reserved for experienced surgeons with new devices and
      technologies, endoscopic sphincterotomies can be performed in different
      situations, discussed in this paper to offer the patient, a modern minimally
      invasive treatment for gallstone disease.

PMID- 8257045
TI  - [Treatment of postoperative incisional hernias by a composite prosthesis
      (polyester-polyglactin 910). Clinical and experimental study].
AB  - Because of complications resulting from the use of intraperitoneal prosthetic
      materials, the authors studied a new double Layered composite mesh (formed by a
      Dacron mesh, and a polyglactin 910 mesh). The experimental study (40 rats)
      compared the composite mesh with Dacron mesh. Statistical analysis demonstrated
      the following conclusions. At 6 months, the poor fibroblastic activity with the
      composite mesh, indicated the absence of replacement of the polyglactin 910 mesh
      by a neo-tissue. The Dacron mesh remained in contact the abdominal viscera and
      contracted with them as many adhesions as when Dacron mesh was used alone. The
      composite mesh showed poor biological tolerance, lower than that of Dacron mesh.
      The clinical study concerned 24 patients, 3 recurrences were observed. In one
      case, we observed migration of the mesh in the small bowel. The unfavorable
      results of the experimentation, and the risk of visceral migration lead us to
      avoid the use of composite mesh in intraperitoneal sites.

PMID- 8257046
TI  - [Repair of inguinal hernia by properitoneal positioning of an ePTFE soft patch
      (112 patches--75 patients)].
AB  - From January 1987 to December 1991, 112 ePTFE patches were inserted in
      properitoneal sites in 75 patients by median (61 patients) or inguinal (14
      patients) approach to cure inguinal hernias. The hernia was direct or combined in
      60 patients, bilateral in 37 patients and recurrent in 37 patients. These 75
      patients accounted for 19.7% of the 380 patients treated for hernia during the
      same period. Complications occurred in 5 patients, 3 of whom needed a second
      operation: 2 periprosthetic seromas, 2 femoral nerve irritations and one
      periprosthetic infection which resolved after treatment without patch removal. No
      patch was removed. Ninety three percent of the patients had an uneventful
      postoperative recovery. All patients were followed (range: 4 months-5 years) for
      an average of 28 months; 88% for one year or more. There were 3 recurrences which
      healed after reoperation. No late infection of sinus occurred. One patient
      complained of severe pain without any attributable cause. One patient had femoral
      hypoesthesia, 7 others suffered slight intermittent pain without any local
      complication. Discomfort in these 8 cases was very mild. Sixty-eight patients
      (91%) rated the result of their surgery as good or excellent. This clinical study
      confirms the biomechanical properties of ePTFE and demonstrates that, in
      comparison with mesh of equal strength, the infection rate and its severity would
      be decreased with ePTFE soft tissue patch.

PMID- 8257047
TI  - [Local recurrence after surgery for cancer of the rectum].
AB  - Local tumor recurrence rates after curative rectal cancer surgery are reportedly
      high and herald a poor diagnosis. Extramural recurrence is most common and is due
      to the failure to remove all of the tumor during the initial operation. In the
      rarer anastomotic recurrence, the implantation of exfoliated malignant cells is
      possible, but histochemical changes in the mucosa surrounding a tumor may be
      considered as an alternative cause of local recurrence. Local recurrence rates
      did not improve when the distal margins were extended over 2 cm, but microscopic
      lateral tumor extension appears to be the major determinant of recurrence. Early
      diagnosis is based on frequent CEA assays, history, physical examination,
      endoscopy, endoluminal ultrasound and pelvic CT scan. Aggressive treatment
      involving a combination of field irradiation, surgical debulking and intra
      operative radiation can result in local control and long-term survival in 10 to
      25% of patients.

PMID- 8257048
TI  - [Abdominal approach of rectocele and colpocele].
AB  - The authors report a series of 62 female patients operated for rectocele and/or
      elytrocele via an abdominal approach. The technique was based on insertion of a
      retrovaginal prosthesis attached to the sacrum. Other surgical procedures can be
      performed at the same operation: hysterectomy, insertion of a prevaginal
      prosthesis, retropubic colpopexy. The anatomical and functional results were
      excellent in these patients previously operated for urinary incontinence or
      prolapse (99%). The indication for total hysterectomy during the same operation
      must be limited as this procedure increases the morbidity and impairs the
      functional results. Dyschexia is improved, but may be followed by postoperative
      constipation. Abdominal treatment of rectoceles and/or elytroceles by
      interposition of an interrectovaginal prosthesis attached to the sacrum is
      particularly indicated after hysterectomy in the case of associated or recurrent
      genitourinary prolapse.

PMID- 8257049
TI  - [Pure dysgerminomas of the ovary. Retrospective analysis of 17 cases treated at
      the Claudius Regaud Center from 1974 to 1989].
AB  - From 1974 to 1989, 17 dysgerminomas of the ovary were treated at the Centre
      Claudius Regaud. The mean age of the patients was 21 years: 53% were FIGO stage
      IA, 17% were stage IB, 6% were stage IIB and 24% were stage IIIC. Conservative
      surgery was performed in 13 patients (unilateral salpingo-oophorectomy) and non
      conservative surgery was performed in the others patients. 70% of the patients
      underwent complete resection. Post-operative treatment was administered in every
      case but one (radiotherapy: 15 patients; combined chemo-radiotherapy: 1 patient).
      All patients achieved complete remission after the first-line treatment, but 2 of
      them recurred (1 IA, 1 IIB). A second remission was achieved in both cases. The
      overall survival rates were 100% at 2 years, 94% at 5 years and 89% at 10 years.
      The dual objective of curing the patient of her malignant disease while
      preserving her reproductive function was achieved in 53% of the patients.

PMID- 8257050
TI  - [Malignant epidermoid degeneration of dermoid cysts of the ovary. Apropos of 2
      cases].
AB  - Malignant transformation of benign ovarian cystic teratomas has been reported in
      0.5 to 2% of cases. Many different types of cancer can develop, including
      squamous cell carcinoma, which is by far the most frequent (75%). The mean age of
      diagnosis is over 50 years. Minimal surgical techniques have been increasingly
      popular and laparoscopic removal of benign ovarian cysts has become common
      practice. Malignant transformation is rare but needs to be recognized in order to
      avoid dissemination of malignant cells during surgery. Direct invasion of the
      adjacent pelvic structures and small intestine represents the most common mode of
      spread. Survival is not improved by post-operative radiotherapy or adjuvant
      chemotherapy in patients with extracapsular disease. We report two cases, one of
      which presented with spontaneous ovarian abscess and paraneoplastic
      hypercalcemia.

PMID- 8257051
TI  - [Ultrasonic endoscopy of superficial epidermoid cancer of the esophagus].
AB  - Superficial squamous cell carcinomas of the oesophagus are defined as cancers
      confined to the mucosa or involving the submucosa but sparing the muscularis
      mucosae, with or without lymph node extension. Although lymph node involvement is
      rare (less than 5%) in tumours confined to the mucosa, it is frequent (30 to 45%)
      in tumours involving the submucosa, which have a prognosis similar to that of the
      usual obstructive tumours. Endoscopic ultrasonography is the most accurate
      examination (diagnostic accuracy greater than 95%) to distinguish between
      superficial and advanced cancers. The absence of visualization of the muscularis
      mucosae with the currently available transducers limits the decision-making value
      of such a distinction except in the case of flat tumours in which the absence of
      ultrasonographically detectable parietal thickening indicates the presence of a
      cancer confined to the mucosa, with an excellent prognosis.

PMID- 8257052
TI  - Thyroid disorders.

PMID- 8257053
TI  - Thyroid disorders in Singapore.

PMID- 8257054
TI  - Thyroid hormones and autoantibodies in pregnant patients with thyroid diseases.
AB  - Serum concentrations of thyroid stimulating hormone (TSH) and thyroid
      autoantibodies in pregnant patients with thyroid disease at various stages of
      pregnancy were determined by in-house ELISAs. In normal pregnancy, serum TSH
      levels were significantly elevated (p < 0.05) from 13 weeks of gestation. The
      normal reference ranges for TSH for the second (0.6-5.0 mIU/l) and third
      trimester (0.6-5.6 mIU/l) were significantly higher (p < 0.05; p < 0.01
      respectively) compared to 0.4-4.5 mIU/l for the first trimester. In pregnant
      thyroid patients, serum TSH levels correlated highly (p < 0.001) to T4 (r =
      0.740), FT4I (r = 0.683) and MicAb (microsomal antibodies) (r = 0.825) but weaker
      (p < 0.01) to T3 (r = -0.512), FT3I (r = 0.520) and TgAb (thyroglobulin
      antibodies) (r = 0.618). Thus, measurement of TSH with the highly sensitive ELISA
      (enzyme linked immunosorbent assay) would form a useful first line test for
      thyroid dysfunction in pregnancy while measurement of thyroid autoantibodies
      would aid in the diagnosis of autoimmune hypothyroidism.

PMID- 8257055
TI  - Occurrence of antibodies to insulin in patients with autoimmune thyroid disease.
AB  - Insulin autoantibodies (IAA) in patients with autoimmune thyroid disease (n = 97)
      were determined by a displacement-based ELISA technique. There were 78 patients
      with Graves' disease and 19 with autoimmune thyroiditis. The assay precision
      unit, standard deviation score, was used to assess the presence of IAA. It was
      determined that 7.2% were assessed to be IAA-positive. None of the patients had
      islet cell antibodies. Thyrotrophin receptor antibodies (TRAb) were only present
      in patients with Graves' disease. The mean TRAb levels in patients who relapsed
      (95.0 +/- 141 IU/l, n = 36) were significantly higher (p = 0.042) than those
      newly diagnosed for Graves' disease (38.3 +/- 36 IU/l, n = 28). Insulin
      autoantibody levels in these two subgroups were not different from each other. In
      addition, TRAb levels were not related to IAA levels. A retrospective study of 12
      patients on carbimazole treatment indicated that modulation of TRAb levels had no
      concomitant effect on the development of IAA.

PMID- 8257057
TI  - Role of technetium-99m sestamibi in localisation of thyroid cancer metastases.
AB  - Technetium-99m sestamibi (MIBI) is a routinely used myocardial perfusion imaging
      agent. We have studied groups of patients with differentiated thyroid carcinoma,
      in order to evaluate the usefulness of this agent in localising regional neck and
      nodal disease and metastases. There are three groups of patients. Group 1
      consisted of patients with known nodal disease or metastases (22 patients) and
      with raised serum thyroglobulin levels (Tg). Group 2 comprised patients with
      normal I-131 scans and normal Tg levels (nine patients). Non-thyroid malignancies
      (six patients) comprised an additional group 3. In group 1, the MIBI scan showed
      47 sites of metastases, while the I-131 scan revealed 49 sites. The MIBI scan was
      positive in two patients where the I-131 scan was negative, while in two other
      patients, the MIBI study was negative whereas the I-131 scan was positive. In
      group 2, 6/9 patients had no disease, 2/9 had thyroid remnants, and 1/9 had a
      fresh primary lung tumour, unrelated to the earlier thyroid cancer. All of them
      had normal MIBI scans. In group 3, two patients with lung cancer and two with
      breast cancer and metastases had normal MIBI scans. A further two patients with
      nasopharyngeal cancer (NPC) had mildly increased MIBI localisation in neck nodes
      and bone metastases. In summary, Tc-99m sestamibi appears to be as good as I-131
      in search for thyroid carcinoma metastatic spread, especially nodal disease and
      this tracer does not localise well in the primary or metastases of other
      cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257056
TI  - Free thyroxine as a supplement to thyrotropin in cord screening for
      hypothyroidism.
AB  - The low specificity of cord serum T4 levels for detecting hypothyroidism, the
      need to reduce recall rates and the availability of a reliable and quick assay
      system led to this study designed to determine the advantages of using cord serum
      free thyroxine levels over total thyroxine levels as a supplement to cord thyroid
      stimulating hormone (TSH) determination. Sixty-eight out of 75 newborns with a
      cord TSH > 23 mU/l had both free thyroxine (fT4) and T4 levels measured in the
      cord serum. All were recalled within the first month of life for reevaluation of
      their thyroid status. In the majority of cases (46), the fT4 and T4 values
      corresponded. Hypothyroidism was diagnosed in eight cases; both fT4 and T4 were
      below the mean in five cases and above the mean in one case; only T4 was below
      the mean in one and in the remaining one, only fT4 was below the mean. Recall
      rates were 0.9% with TSH alone and 0.7% when either a fT4 or T4 level that was
      less than 1 sd above the mean was used as a supplement to TSH. In this cohort,
      using the fT4 levels instead of the T4 levels brought no change to the
      specificity or the sensitivity of the screening. The diagnostic sensitivity would
      have dropped from 100% to 75% if either T4 or fT4 values below the mean were used
      as a cut-off point for recall.

PMID- 8257058
TI  - Investigation of thyroid nodules using technetium-99m sestamibi.

PMID- 8257059
TI  - Racial disparity in the prevalence of thyroid disorder during pregnancy.
AB  - A study to determine the prevalence of goitre and abnormal thyroid status during
      pregnancy in Malaysian women was conducted. Two hundred and three women (Malay =
      85, Chinese = 47 and Indian = 71) in the third trimester and with no known
      thyroid disease were studied. There was a marked racial disparity in the
      prevalence of goitre: Indian 61%, Malay 28% and Chinese 29% (p = 0.001). The
      serum thyrotropic hormone (TSH) was significantly higher in Indians (median: 1.36
      uIU/ml) compared to Malays (1.14 uIU/ml, p = 0.009). The serum albumin was also
      significantly lower in Indians (mean +/- sd; 36.12 +/- 3.9 mmol/l) compared to
      Malays (39.3 +/- 4.8 mmol/l) or Chinese (39.1 +/- 5.2) (p < 0.001). Thyroid
      antibody was detected in 14.6% of these women with no significant racial
      difference in its prevalence. Three women were found to be thyrotoxic but none
      were hypothyroid. This study found a high prevalence of goitre among the pregnant
      Indian women, probably related to the protein malnutrition state. The high
      prevalence of positive thyroid antibody in our population indicates that a high
      percentage of women are at risk of developing postpartum thyroiditis.

PMID- 8257060
TI  - Acetylcholine receptor antibody assay kit: establishment of controls in normals
      and non-myasthenics and evaluation of sera from patients with thyroid disease.
AB  - Immunoprecipitation assays for antibodies to the nicotinic acetylcholine receptor
      are a specific test for the diagnosis of myasthenia gravis. However, testing has
      largely been confined to reference laboratories because the preparation of the
      reagents is laborious, making it less accessible to practising clinicians
      locally. We recently acquired a test kit produced by RSR Ltd (Avenue Park,
      Pentwyn, Cardiff) which makes testing of serum samples practicable in smaller
      centres. We describe our experience in establishing normal and control values in
      30 separate samples. We also assayed the sera of ten patients with thyroid
      disease, some of whom had ophthalmopathy and/or weakness due to periodic
      paralysis, and none of these tested positive. Three additional patients with
      thyroid disease and concurrent myasthenia gravis were also inadvertently included
      in the latter assay and two had high titres and one had equivocal titres. The
      assay is now run regularly every quarter of the year.

PMID- 8257061
TI  - Clinical features, investigations and pathology in surgically treated
      thyrotoxicosis.
AB  - A retrospective study was conducted on 41 thyrotoxic patients operated from
      January 1986 to June 1992 in Alexandra Hospital. One had multinodular goitre, and
      the rest had autoimmune thyroid diseases. Analysis of the histopathological
      features of the 40 patients with autoimmune thyroid diseases revealed that 32 had
      Graves' disease, four had Hashimoto's thyroiditis and four had a mixed form of
      Graves' disease and Hashimoto's thyroiditis. Only 14 out of 32 patients had eye
      and/or cutaneous manifestation of Graves' disease. None of the patients with
      Graves' disease developed hypothyroidism over a mean follow-up period of two
      years post-operatively, whereas one out of four Hashimoto's thyroiditis and two
      out of the four with the mixed form of Graves' and Hashimoto's thyroiditis had
      hypothyroidism after surgery. We conclude that it may be difficult to make a
      diagnosis of Hashimoto's thyroiditis in the early phase when it presents with
      thyrotoxicosis. Besides, there are cases with a mixed form of both Graves' and
      Hashimoto's thyroiditis. However, it is important that the diagnosis of
      Hashimoto's thyroiditis be made before surgery, otherwise progression to
      hypothyroidism would be accelerated.

PMID- 8257062
TI  - Human leucocyte antigen DNA typing in Singaporean Chinese patients with Graves'
      disease.
AB  - Human Leucocyte Antigen (HLA) A, B, C, DR, DQ and DP locus alleles in 35 Chinese
      patients with Graves' disease and 80 controls were typed for using serological
      and DNA polymerase chain reaction/sequence specific oligonucleotide (PCR/SSO)
      methods. B46 was found to be strongly associated with male patients (p = 0.0002;
      RR = 8.2, 95% confidence interval 2.1-32.2). In HLA class 1 alleles, besides B46,
      the frequencies of A2 and Cw1 were increased and A24 and B63 decreased in
      patients compared to controls. In HLA class 2 alleles, the frequencies of
      DRB1*1602, *0301, *1405, DRB5*02, DQB1*0502 were increased and DRB1*1501,
      DQB1*0301 decreased in patients.

PMID- 8257063
TI  - Tuberculosis of the thyroid gland--a review.
AB  - A review of the literature reveals that tuberculosis of the thyroid gland is a
      very rare condition. Only one case was notified in Singapore over the last ten
      years. It can occur either as part of a miliary spread or as a primary lesion in
      the thyroid. It is difficult to diagnose clinically and the thyroid enlargement
      is often mistaken for carcinoma, suppurative abscess or a haemorrhage into a
      thyroid cyst. Signs and symptoms are variable, and are mostly related to
      enlargement of the gland. Thyroid dysfunction is rare. Diagnosis is made by
      histological examination and demonstration of the tubercle bacilli from biopsy or
      aspiration specimen.

PMID- 8257065
TI  - Postpartum thyroid dysfunction: a viewpoint from Thailand.
AB  - Postpartum thyroid dysfunction (PPTD) refers to changes in thyroid function that
      occur during the first 12 months postpartum. The changes in thyroid function can
      either be thyrotoxicosis or hypothyroidism which may be transient or permanent in
      nature. The aetiology is multiple, including postpartum thyroiditis, new onset or
      exacerbation of Graves' disease, exacerbation of primary hypothyroidism due to
      Hashimoto's thyroiditis, central hypothyroidism due to postpartum pituitary
      necrosis or central hypothyroidism due to lymphocytic hypophysitis. There is a
      paucity of data concerning PPTD in South East Asia. However, available data
      indicate a seemingly high prevalence of central hypothyroidism due to postpartum
      pituitary necrosis in Thailand. The alterations in the course of Graves' disease
      during pregnancy and postpartum are similar to those reported elsewhere. However,
      the dosage of antithyroid drug used during pregnancy in Thai women is quite
      small. The lower environmental iodine in Thailand may be one of the responsible
      factors. Interestingly, the prevalence of PPTD due to postpartum thyroiditis
      reported from Thailand was only 1.1% which was less than that reported in other
      countries. The discrepancy in the geographic prevalence of postpartum thyroiditis
      may result from the interaction of immunogenetic heterogeneity of different
      ethnic background, environmental iodine intake, and other unidentified
      environmental factors.

PMID- 8257064
TI  - Thyroxine replacement therapy.
AB  - There is much debate about what is the correct dose of thyroxine replacement
      therapy and whether suppression of the serum TSH concentration, when measured by
      an assay with a lower limit of detection of 0.1 mU/l or less, is a risk factor
      for osteoporosis. Nor is there agreement about whether patients with subclinical
      hypothyroidism are at an increased risk of developing ischaemic heart disease.
      Normalisation of serum TSH in such patients is by no means a universal policy.
      Increasingly, it is recognised that hypothyroidism may be temporary and may even
      remit spontaneously after many years of treatment with thyroxine.

PMID- 8257066
TI  - The solitary thyroid nodule revisited.
AB  - A series of 195 clinically solitary thyroid nodules is presented and compared
      with a matching series reported a decade ago. Changes in the pattern of
      presentation, preoperative diagnosis and options of operative management are
      highlighted. Although the pattern of presentation has not changed significantly
      over the last decade, there was a shift noted towards reliance on fine needle
      aspiration for preoperative diagnosis. The false negative rate was two percent in
      this series and there were no false positives. There was also a shift towards
      more conservative surgery in the form of "nodulectomies" in the present series
      compared to the previous one. The incidence of malignancy in this series was 10.2
      percent.

PMID- 8257067
TI  - Langerhans cell histiocytosis presenting as a goitre: a case report.
AB  - We report a case of Langerhans cell histiocytosis (histiocytosis X) in a 36-year
      old female with an euthyroid nodular goitre as the rare initial presentation. She
      subsequently developed a pathological fracture of the lumbar spine which was
      initially thought to be due to malignant infiltration, possibly from metastatic
      thyroid carcinoma. Open vertebral biopsy and total thyroidectomy were performed.
      Histological features of histiocytic proliferation with erythrophagocytosis were
      found in both the thyroid gland and in the involved vertebral body. The diagnosis
      of histiocytosis X was made on the basis of the positive immunoperoxidase
      staining of the histiocytic cells with S-100 and peanut agglutinin (PNA) as well
      as the clinical picture. Despite systemic chemotherapy with low dose
      corticosteroids and vinblastine, diabetes insipidus with a suprasellar mass
      occurred three years post thyroidectomy. Successful management of this uncommon
      disease is difficult to conduct and evaluate at the present time.

PMID- 8257068
TI  - Hyperthyroidism and Down syndrome.
AB  - Down syndrome has long been associated with a variety of autoimmune conditions. A
      significant link has also been described between Down syndrome and autoimmune
      thyroid disease, usually hypothyroidism. We report two cases of Down syndrome
      with Graves disease both with significantly elevated titres of thyrotropin
      receptor antibody and the presence of the HLA Bw46. We also comment on the
      problems in diagnosis and management of such patients.

PMID- 8257069
TI  - Primary papillary carcinoma in a thyroglossal cyst--a case report.
AB  - A benign thyroglossal cyst is a common clinical condition and is second only to a
      cervical lymph node as the most common cause of a solitary neck swelling. Primary
      carcinoma of a thyroglossal cyst, however, is rare and has been described in only
      115 cases in the literature. The malignant cysts are clinically difficult to
      differentiate from benign lesions and the diagnosis often rests on
      histopathological examination. Before initiating treatment, primary papillary
      carcinoma of the thyroid gland must be excluded. The treatment options range from
      simple excision to a Sistrunk operation with concurrent cervical lymph node
      dissection. We describe here a case of papillary carcinoma of a thyroglossal cyst
      and review the 115 reported cases.

PMID- 8257070
TI  - Conduction abnormalities in thyrotoxicosis--a report of three cases.
AB  - Cardiac arrhythmias are common in patients with thyrotoxicosis. Conduction
      abnormalities have been seen in a few thyrotoxic patients, but these, in
      particular high grade atrioventricular (AV) block, often occur in the presence of
      other conditions. Three thyrotoxic patients with conduction abnormalities are
      described: two were associated with severe hypokalaemia and the third had
      congestive cardiac failure. Conditions predisposing to conduction abnormality
      should be identified when this occurs in a thyrotoxic patient as their correction
      may help resolve or explain the conduction abnormality.

PMID- 8257071
TI  - Thyroid cancer in the 1980s--a decade of change.
AB  - Changes in the 1980s in thyroid cancer included an increased incidence of
      papillary carcinoma and a decrease in anaplastic carcinoma in the UK; the
      establishment of cytology as the prime agent in diagnosis; and total
      thyroidectomy became the operation of choice in many centres and block
      dissections gave way to local node removal. Thyroxine was shown to give
      significant improvement in survival. Histological type remained the prime factor
      in prognosis with papillary carcinoma showing excellent long-term survival rates
      compared to follicular carcinoma, while anaplastic carcinoma had few survivors
      over two years (log rank X2 = 304.57, p < 0.005). In the totality of thyroid
      tumours, excluding consideration of the histology, we found that increasing age,
      progression of stage T1 and T3 and stage M1 all contributed to reduce survival
      and that females outlived males. We contrasted technical aspects in total and sub
      total lobectomy and showed that the more radical procedures reduced local
      recurrence at the price of increased parathyroid and nerve damage without
      evidence of improved long-term survival. We found that the critical factor in
      surgical results was whether the operation cleared all cancer from the neck and
      suggested near total thyroidectomy as the standard procedure in follicular cell
      tumours, reserving total thyroidectomy for gross bilateral spread.

PMID- 8257072
TI  - Major blinding complications of intraocular implantation.
AB  - Modern implant surgery for cataract by trained ophthalmologists gives excellent
      results in the vast majority of patients. All eye surgeons have a grave
      responsibility to ensure that blinding complications are avoided. The major
      blinding postoperative complications include endophthalmitis, problems with lens
      implants, corneal decompensation, uveitis and glaucoma, retinal complications and
      inadequate microsurgical training. The most disastrous of these is postoperative
      endophthalmitis which is preventable and can result in total blindness.

PMID- 8257073
TI  - Continuous ambulatory peritoneal dialysis in type II diabetics.
AB  - Forty-two Type II diabetic patients with end stage renal failure who had never
      previously received dialysis treatment were treated with continuous ambulatory
      peritoneal dialysis (CAPD) for a period of two to 48 months (average 16.8 months)
      with a total experience of 640 patient-months. Of the 42 patients, 29 (69%) were
      male and 13 (31%) were female. The mean duration of diabetes before dialysis was
      12 years. Eleven patients (40%) were on dietary control alone, seven patients
      (24%) on oral hypoglycaemic control and ten patients (36%) on insulin treatment.
      Blood glucose control between these groups did not differ significantly. There
      was a significant gain in dry weight from a mean of 60.3 kg prior to dialysis to
      74 kg two years after dialysis. There was no significant improvement in the
      haemoglobin level. Blood triglyceride levels increased from 214 +/- 63 mgm/dl to
      283 mgm +/- 156 mgm/dl with an insignificant reduction in the cholesterol level.
      Serum calcium levels increased significantly from 8.0 +/- 1.3 to 9.1 +/- 1.0
      mgm/dl in 12 months (p < 0.05). Serum alkaline phosphatase level remained stable.
      Blood pressure was stable throughout the dialysis period. Adequacy of dialysis
      clearance was shown by the mean value of serum urea 115 +/- 40 mgm/dl, serum
      creatinine 10.6 +/- 2.7 mgm/dl and serum phosphate 4.65 +/- 1.6 mgm/dl after two
      years on CAPD. No peritoneal membrane failure was reported.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8257074
TI  - Fetal salvage in maternal systemic lupus erythematosus.
AB  - Fifty-two pregnancies in 30 patients with systemic lupus erythematosus were
      studied prospectively. There were two spontaneous abortions, two therapeutic
      terminations for active disease, two intrauterine deaths before 28 weeks and one
      stillbirth. Forty-five (86.6%) pregnancies had a successful outcome. Five
      patients had renal involvement before or during pregnancy whilst 12 (23%) had
      preeclampsia. Placental insufficiency and intrauterine hypoxia contributed to a
      high Caesarean section rate (44%). The selection of patients for pregnancy,
      optimal medical care, antenatal monitoring and intensive neonatal care have
      improved fetal salvage in this condition.

PMID- 8257075
TI  - Nasopharyngeal carcinoma--a review of radiotherapy techniques.
AB  - With modern megavoltage external X-ray treatment for nasopharyngeal carcinoma,
      results have improved but late sequelae, which are more often associated with the
      treatment of advanced tumours or multiple courses of external treatment, have
      also surfaced. Life-threatening complications include temporal lobe necrosis and
      hypothalamic-pituitary dysfunction. As CT scanning is superior to conventional
      radiography in tumour mapping, a new dedicated working staging system, catering
      for cross-sectional imaging parameters, is proposed for a prospective, multi
      centre exercise to finalise on a badly needed common system. With it, case
      selection for more conservative (to minimise complications) or intensified
      treatments is facilitated. Intracavitary radiation has now been developed well
      enough for the nasopharynx. For earlier cases, based on the new staging system,
      this method has the potential to complement a "sub-radical" external treatment
      dose designed to minimise complications. A multi-centre trial is indicated. To
      reach cancericidal doses for the more advanced tumours coming very close to vital
      structures, extra machine time, though precious, is fully justified so that
      smaller treatment fractions delivered with facial shells for accurate
      reproduction of precise machine geometry and field geography can be implemented.
      Otherwise, subsequent management of possible serious treatment complications may
      cost more than the treatment itself. Various possible complications of
      radiotherapy and avoidance and management are outlined.

PMID- 8257076
TI  - Galloway Memorial Lecture. Protein engineering of tumor necrosis factor-beta and
      its applications in cancer, septicaemia and cachexia.
AB  - The tumour necrosis factors (TNFs) are cytokines, small proteins produced by
      cells as part of the intercellular signalling network. The exact physiological
      role of TNFs is unknown, but interest in them focused on three of their
      capabilities: as potential anti-tumour agents, as humoral mediators of an
      organism's response to injury and as effector molecules in cachexia. The first
      TNF to be described, now known as TNF-alpha, has been relatively well studied
      because the recombinant protein was easily produced since it was cloned in 1984.
      Studies on TNF-beta or lymphotoxin were hampered by the inability of most groups
      to express the recombinant protein. This paper describes the expression and
      purification of recombinant TNF-beta in Escherichia coli, followed by studies to
      localise the receptor binding site of the molecule through site-directed
      mutagenesis. Mutants with single amino acid changes at either of two distinct
      loop regions, at positions aspartic acid-50 or tyrosine-108, were found to have
      greatly reduced receptor binding and cytotoxic activity. These two regions in TNF
      beta correspond to known loop regions where mutations also result in loss of
      biological activity of TNF-alpha, a related cytokine which shares the same
      cellular receptors with TNF-beta. This provides evidence for a new hypothesis
      that both the TNFs bind to their receptors as trimers, each of which is capable
      of binding simultaneously to three receptors. This leads further to the
      intriguing possibility of a new mechanism of receptor clustering through
      simultaneous binding to a single ligand.

PMID- 8257077
TI  - Adiposity in Czech children followed from 1 month of age to adulthood: analysis
      of individual BMI patterns.
AB  - In Czechoslovakia, overweight and nutrition-associated pathologies are frequent.
      The body mass index (BMI) is often used in the clinical assessment of adiposity
      in children and adults. Its variations during growth are well documented. A
      cohort of 300 newborns were selected at random in Prague between 1956 and 1960.
      Weight and height were collected in these subjects at the ages of 3, 6, 9, and 12
      months and twice a year from 1 to 20 years. Charts of longitudinal variations of
      the BMI were drawn for males and females. The three expected phases of BMI
      development were observed: initial rise until 12 months, subsequent decrease, and
      second augmentation (the 'adiposity rebound', 'AR') between 4 and 8 years of age.
      The inverse relationship between age at AR and the BMI in adulthood was
      confirmed: in the leanest adults, AR had happened by age 7.6 years, in the
      heaviest adults, age at AR was around 5 years. Many lean (44%) and fat (58%)
      infants developed into average-size adults. The risk of becoming a heavy adult
      was increased in fat infants (31%) as opposed to non-fat (22%) ones. The relative
      risk of fat infants to become obese adults as compared to non-fat infants is
      31/22 = 1.8. Individual growth curves of children with very high or very low
      adult BMI values illustrate the relationships between BMI at 12 months, age at AR
      and adult BMI. The Czech BMI distribution was higher than a comparable French one
      at all percentiles after age 7 years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257078
TI  - A serial study of normal facial asymmetry in monozygotic twins.
AB  - Asymmetry of the soft tissues of the face was measured by comparing three pairs
      of bilateral facial parameters connecting the landmarks external canthus, tip of
      nose and angle of mouth. The subjects were six pairs of monozygotic twins (eight
      girls and four boys) in the age range 8-19 years. A clinical contour mapping
      technique known as short-base stereophotogrammetry provided life-size facial maps
      on which the parameters were measured in three dimensions. The study was based on
      annual serial records over an average period of 9 years for each pair, and was
      almost entirely longitudinal. The asymmetry in millimetres was given a positive
      or negative sign, depending on whether right or left side dominated. Asymmetry in
      the facial parameters was found to be very small, amounting at most to a few
      millimetres, and was not much larger than the measuring error of the method.
      Nevertheless, asymmetry was statistically significant (p < 0.05) in 12 out of 60
      indicators, and of these seven were at p < 0.01 level. Asymmetry could not be
      related to twin zygosity, adolescence or age.

PMID- 8257079
TI  - Inbreeding effects on prereproductive mortality: a case-control study in Saguenay
      Lac-Saint-Jean (Quebec, Canada) based on a population registry 1838-1971.
AB  - Effects of inbreeding on the prereproductive mortality, excluding spontaneous
      abortions, were investigated among offspring of 251 marriages between first
      degree cousins (2:2) and 358 marriages between first-degree cousins once removed
      (2:3) from Saguenay-Lac-Saint-Jean. A control group matched on the demographic
      and socioeconomic characteristics of the consanguineous marriages was created.
      The mortality rates were calculated from a computerized population registry. The
      stillbirth rate was not significantly higher in the 2:2 and 2:3 groups compared
      with their respective control groups (p > 0.05). Mortality during the first year
      was significantly higher in both consanguineous groups (p < 0.01) whereas
      mortality between 1 and 15 years was not (p > 0.05). In Saguenay-Lac-Saint-Jean,
      less than 1% of the prereproductive mortality, excluding spontaneous abortions,
      can be attributed to consanguineous marriages. This study is in agreement with
      previous reports showing that inbreeding had a minor impact in prereproductive
      mortality.

PMID- 8257080
TI  - Inbreeding effects on fertility and sterility: a case-control study in Saguenay
      Lac-Saint-Jean (Quebec, Canada) based on a population registry 1838-1971.
AB  - Effects of inbreeding on couples' fertility and primary sterility were
      investigated in five marriages between uncle and niece, 251 marriages between
      first-degree cousins, and 358 marriages between first-degree cousins once removed
      from Saguenay-Lac-Saint-Jean. Three control groups matched on the demographic and
      socioeconomic characteristics of the consanguineous couples were created. The
      number of children born to each couple was extracted from a computerized
      population registry. The level of primary sterility was found to be similar in
      all consanguineous and non-consanguineous groups. The mean number of children in
      all three consanguineous groups was not found to be significantly different from
      that calculated in their respective control groups (p > 0.05). These results are
      compatible with those obtained in virtually all the studies reported thus far in
      different populations.

PMID- 8257081
TI  - Fluctuating dermatoglyphic asymmetry: genetic and prenatal influences.
AB  - Genetic and environmental prenatal factors influencing the fluctuating asymmetry
      of the a-b interdigital ridge count are examined. From the results obtained we
      can conclude that fluctuating asymmetry of the a-b interdigital ridge count is
      poorly influenced by genetic factors. We suggest that fluctuating asymmetry of
      dermatoglyphics provides a good measure of developmental stability in humans,
      especially for males. The results also indicate that random environmental
      factors, acting before the 19th week of embryonic development, could be related
      to the differential timing of maturation of the sexes.

PMID- 8257082
TI  - Population structure and immigration; a study of the Valserine valley (French
      Jura) from the 17th century until the present.
AB  - The establishment of the genealogies and biographies of inhabitants of selected
      villages from the Haut-Jura from the 17th century up to the present day has
      enabled us to demonstrate the major role of immigration on the genetic structure
      of a population. The evaluation of the effective descendance of native versus
      immigrant couples shows the imbalance of demographic contribution in favour of
      the first category. Immigrant couples account for 26% of all couples with at
      least one offspring in the valley, but account for 7.2% of all couples with an
      effective descendance. In our opinion, this effective immigration reflects in a
      much better way the measurement of immigration impact on population genetic
      parameters, especially the genetic 'opening' of the population due to
      immigration. This measurement of the effective descendance divides the population
      into two major groups: a core of stable lineage characterized by 70% of couples
      with an effective descendance, 'surrounded' by an unstable group from which only
      30% of couples have an effective descendence in the population. Furthermore, from
      any given point in time this difference between the two groups can be observed
      among their descendants during the following generations. The existence of such a
      core can be explained by the social history of the valley, and shows that any
      specific unfavorable genetic fostered by the core can be locked within the
      population and transmitted throughout generations.

PMID- 8257083
TI  - Respiratory adaptation to high altitude in adolescent Bod girls of the Western
      Himalayas.
AB  - The impact of high-altitude environment was studied on respiratory functions and
      body measurements in adolescent Bod girls of Ladakh, Jammu and Kashmir, India.
      Data were collected on 133 high-altitude and 141 low-altitude Bod girls in the
      age range 12-18 years. Lung functions were, age to age, higher in high-altitude
      girls than their coeval lowlanders. This has been explained as an adaptation to
      the stress of low atmospheric pressure at high altitude. This response is similar
      to the one observed in growing Bod boys living in the same area (Malik and Singh
      1979, 1984). High-altitude girls were shorter and lighter, the difference was
      more pronounced in weight and especially after 14 years of age.

PMID- 8257084
TI  - Secondary sexual development in rural and urban South African black children.
AB  - The timing and duration of secondary sexual development in two samples of rural
      and urban South African black children were investigated using the Tanner staging
      techniques and compared to similar data from Switzerland and England. In general
      rural black children were consistently delayed in the age at which they entered
      the events of puberty, and took longer to pass through each of the stages. Urban
      black children, from good socioeconomic backgrounds, were advanced in relation to
      their rural peers and slightly ahead of the European samples. There were no
      significant differences in the sequence of events. Estimates of testicular volume
      on the well-off urban boys demonstrated that they exhibited similar volumes to
      European boys at similar ages. It is suggested that the British clinical
      longitudinal growth standards could be effectively used to sensitively monitor
      the growth and maturation of black urban children from good socioeconomic
      backgrounds.

PMID- 8257085
TI  - A case study of daily growth during adolescence: a single spurt or changes in the
      dynamics of saltatory growth?
AB  - Standing height of one adolescent male was measured daily between the ages of
      12.83 and 13.95 years on 328 days out of 389 consecutive days according to
      standard techniques for maximal stature measurement. The serial growth data were
      analysed by a modification of techniques developed to identify patterns in serial
      hormone data. The entire growth in height during this interval occurred during 12
      non-periodic saltatory episodes with amplitude of 0.92 +/- 0.09 cm (SEM) in < or
      = 24 h separated by 3-100 days of no significant growth. The proposition that
      adolescent growth is characterized by a change in the dynamics of growth saltus
      amplitude and/or frequency is suggested.

PMID- 8257086
TI  - Germline rearrangement of MCC and APC detected by pulsed field gel
      electrophoresis and fluorescent in situ hybridization.
AB  - Pulsed field gel electrophoresis was carried out on lymphocyte DNA obtained from
      ten patients with the inherited premalignant condition adenomatous polyposis coli
      and a similar number of control samples to search for large scale molecular
      rearrangements in the vicinity of the APC locus. DNA from one patient showed a
      rearranged pattern which was interpreted as evidence for an inversion of
      approximately 150 kb, changing the transcriptional orientation of the
      neighbouring MCC gene and bringing it closer to APC. Such an interpretation was
      supported by fluorescent in situ hybridization data.

PMID- 8257087
TI  - Regional localization of the lactase-phlorizin hydrolase gene, LCT, to chromosome
      2q21.
AB  - The gene LCT which codes for the intestinal disaccharidase lactase-phlorizin
      hydrolase has previously been mapped, using somatic cell hybrids and linkage
      analysis, using the CEPH families, to chromosome 2. We describe here the regional
      localization of LCT to chromosome 2q21 by polymerase chain reaction (PCR)
      analysis of somatic cell hybrids and in situ hybridization. LCT is closely linked
      to D2S44, with a lod score of 30.6 at theta = 0.10.

PMID- 8257088
TI  - Regional localization of the gene coding for the GM2 activator protein (GM2A) to
      chromosome 5q32-33 and confirmation of the assignment of GM2AP to chromosome 3.
AB  - The gene coding for the GM2 activator protein (GM2A) was previously mapped by us
      to chromosome 5 by an ELISA-based technique. Here we confirm this assignment
      using a PCR analysis of somatic cell hybrids and describe a regional localization
      to chromosome 5q32-33 by in situ hybridization. We also confirm the assignment of
      a pseudogene GM2AP to chromosome 3.

PMID- 8257089
TI  - Localization of the retinoid X receptor alpha gene (RXRA) to chromosome 9q34.
AB  - The retinoid X receptor alpha is one of a number of retinoic acid receptors which
      are members of the steroid/thyroid hormone superfamily. Localization of RXRA was
      achieved using the polymerase chain reaction on a panel of somatic cell hybrids.
      A cosmid clone was isolated using the RXRA PCR product, and this was used to
      further localize the gene by fluorescence in situ hybridization to chromosome
      9q34 distal to the dopamine beta hydroxylase gene (DBH). This mapping position
      was confirmed by PCR on a panel of translocation hybrids.

PMID- 8257090
TI  - Mapping of RXRB to human chromosome 6p21.3.
AB  - Retinoid X Receptor beta (RXRB) is a member of the retinoid X receptor (RXR)
      family of nuclear receptors which are involved in mediating the effects of
      retinoic acid (RA). We have confirmed the localization of RXRB to chromosome 6
      and we have mapped the gene to chromosome 6p21.3-p21.1 by PCR amplification of 5'
      untranslated sequence in panels of rodent-human somatic cell hybrids and to
      6p21.3 by fluorescent in situ hybridization.

PMID- 8257091
TI  - Sex ratio and natural selection in humans: a comparative analysis of two
      Caucasian populations.
AB  - In the course of the last century industrialized countries have experienced
      significant changes in mortality rates. Since the sex ratio of a population may
      be considered a function of, among other factors, differential mortality in the
      two sexes, it is expected to correlate with changes in sex-specific mortality
      rates. In this paper secular changes in the sex ratio at birth and after the
      action of relevant components of early selection (stillbirth, mortality within
      the first month and within the first year of life) have been studied in the
      Italian and in the USA White populations. The results can be summarized as
      follows. (i) In the past, extra male-specific mortality appeared to reduce the
      relatively large values of the sex ratio observed at birth, and this held true in
      both populations. (ii) In more recent times, male-specific mortality has been
      decreasing in all age groups, and the sex ratios before and after the action of
      early selection now tend to identical values. Therefore, it can be envisaged that
      in the near future the sex ratio observed at birth will be maintained up to the
      reproductive age. If the reproductive value is stabilized by natural selection,
      as is likely, new relationships between sex ratio and selection may be expected
      to develop in a relatively short time.

PMID- 8257092
TI  - A new approach for interpreting the genetic diversity in space: 'Mobile Site
      Method'. Application to Gm haplotype distribution of twenty-seven Amerindian
      tribes from North and Central America.
AB  - We present a new approach, called 'Mobile Site Method' (MSM), to the construction
      of 'genetic similarity maps' more efficient than that described in a preceding
      paper (Hazout et al. 1991). After building a triangular mesh between the
      geographical sites, the method consists of moving these locations at each
      iteration to reduce the overall differences between the geographic and genetic
      distances. The genetic similarity map, i.e. the final distorted map, allows the
      interpretation of the genetic diversity of a population set. We have applied this
      method to the study of Gm immunoglobulin allotypes of twenty-seven Amerindian
      groups from North and Central America. By a local weighted linear regression, we
      have reconstituted the distorted contour of America. This representation
      completes the observations of the sites during the map distortion. In this study,
      we have defined a large geographical factor in the genetic data (84% of the
      variability explained), related to a linguistic factor.

PMID- 8257093
TI  - Testing for haplotype concordance with incomplete parental data--modified Q and
      correction for modified N.
AB  - Some errors have been found in the distribution of modified N in a paper by Green
      & Grennan (1991). These have now been corrected, also a modified form of a new
      test--criterion Q is presented. Both are applied to data.

PMID- 8257094
TI  - Reflections of a microbiologist, or how to learn from the microbes.
AB  - This autobiographical chapter summarizes the author's work with a defined mineral
      medium for fastidious sulfide-oxidizing phototrophic purple and green sulfur
      bacteria that were known already from Winogradsky's and Lauterborn's
      descriptions. The pure cultures, isolated from natural mud deposits, revealed
      interesting new cytological and biochemical features. In the wake of these
      studies, new anaerobic bacteria with unusual metabolic capacities were isolated
      and characterized. Ecologically most significant is the dehydrogenation of
      acetate to carbon dioxide. Electron acceptors are sulfur for the sulfur reducers
      and sulfate for the new sulfate reducers obtained by Widdel. Thauer and Fuchs
      showed that a modified TCA-cycle and the new acetyl-CoA:carbon monoxide
      dehydrogenase pathway operates in the oxidation of acetate. Many aliphatic and
      aromatic compounds were shown to be completely degradable by marine sulfate
      reducers. The biogeochemical transformations of the anoxic sulfur cycle are now
      understood in terms of the capacities of the phototrophic and chemotrophic
      bacterial species involved in the cycle.

PMID- 8257095
TI  - Molecular determinants of the virulence and infectivity of California serogroup
      bunyaviruses.
AB  - California bunyaviruses cause encephalitis in mammalian hosts after peripheral
      infection. The virulence of these viruses is determined by their ability to
      replicate sequentially in striated muscle, cause viremia, and invade and
      replicate in the central nervous system. These viruses are also able to infect
      vector mosquitoes following ingestion of a blood meal containing virus.
      Bunyaviruses are negative stranded RNA viruses with a trisegmented genome, and
      the large, medium, and small RNA segments encode the polymerase, the
      glycoproteins, and the nucleoprotein, respectively. Reassortants between virulent
      and avirulent virus clones have been used to map virulence determinants in mice
      as well as determinants of infectivity in mosquitoes. Attenuation in mice and
      infectivity in mosquitoes of some virus clones maps to the medium RNA segment,
      implying that the virus glycoproteins, which are involved in virus entry, play a
      role in virulence. Attenuation in mice and mosquito infectivity of other clones
      maps to the large RNA segment, suggesting that cell-specific differences in the
      function of the viral polymerase can also determine virulence and host range.

PMID- 8257096
TI  - Suicidal genetic elements and their use in biological containment of bacteria.
AB  - The potential risks of unintentional releases of genetically modified organisms,
      and the lack of predictable behavior of these in the environment, are the subject
      of considerable concern. This concern is accentuated in connection with the next
      phase of gene technology comprising deliberate releases. The possibilities of
      reducing such potential risks and increasing the predictability of the organisms
      are discussed for genetically engineered bacteria. Different approaches towards
      designing disabled strains without seriously reducing their beneficial effects
      are presented. Principally two types of strain design are discussed: actively
      contained bacteria based on the introduction of controlled suicide systems, and
      passively contained strains based on genetic interference with their survival
      under environmental-stress conditions.

PMID- 8257097
TI  - Transport of nucleic acids through membrane channels: snaking through small
      holes.
AB  - Transport of nucleic acids through cell membranes is an essential biological
      process that occurs in all living organisms. This review focuses on two plant
      systems in which nucleic acid molecules are transported through membrane
      channels: transport of Agrobacterium T-DNA through nuclear pores and movement of
      plant viruses through intracellular connections. To provide a broader
      perspective, nuclear uptake of animal viruses and nuclear import/export of small
      nuclear (sn) RNA and messenger (m) RNA are described. By comparing the examined
      cases of nucleic acid transport, the review proposes a set of general rules for
      this type of transport through membrane channels.

PMID- 8257098
TI  - The cell cycle of Escherichia coli.
AB  - For E. coli cells, growth to a critical mass leads to initiation of chromosome
      replication. Initiation requires ATP-bound DnaA protein, together with
      replication proteins. Replication is followed by decatenation and monomerization
      of sister-chromosome molecules. Sister chromosomes are rapidly partitioned into
      opposite halves of the cell, perhaps by a kinesin-like protein (MukB).
      Cytokinesis starts with the formation of a ring of a GTP-binding protein (FtsZ),
      usually around the cell center. A specific enzyme (PBP3) and other proteins
      (FtsQ, FtsA, FtsL, FtsW) are responsible for the coordinate ingrowth of the
      peptidoglycan cell wall at this location. EnvA protein is required to split the
      resultant cross-wall to form new cell poles. The formation of the FtsZ ring is
      inhibited by activated MinC protein, but the MinE protein reverses this
      inhibition at potential division sites. A minimum cell length is probably
      required for partition and a minimum-size DNA-free zone for septum formation.

PMID- 8257099
TI  - Chromosome segregation in yeast.
AB  - Because of their genetic tractability, much has been learned concerning the
      mechanisms of chromosome segregation in budding yeast, Saccharomyces cerevisiae,
      and fission yeast, Schizosaccharomyces pombe. This chapter reviews the cytology
      and molecular and cell biology of mitosis in both of these yeasts. Current
      knowledge about the components of the mitotic spindle apparatus, including
      spindle pole bodies, centromeres, and microtubule components and motors, is
      summarized. Mechanisms of mitosis such as establishment and positioning of the
      mitotic spindle apparatus, anaphase A, and anaphase B are reviewed.

PMID- 8257100
TI  - Dissimilatory metal reduction.
AB  - Microorganisms can enzymatically reduce a variety of metals in metabolic
      processes that are not related to metal assimilation. Some microorganisms can
      conserve energy to support growth by coupling the oxidation of simple organic
      acids and alcohols, H2, or aromatic compounds to the reduction of Fe(III) or
      Mn(IV). This dissimilatory Fe(III) and Mn(IV) reduction influences the organic as
      well as the inorganic geochemistry of anaerobic aquatic sediments and ground
      water. Microorganisms that use U(VI) as a terminal electron acceptor play an
      important role in uranium geochemistry and may be a useful tool for removing
      uranium from contaminated environments. Se(VI) serves as a terminal electron
      acceptor to support anaerobic growth of some microorganisms. Reduction of Se(VI)
      to Se(O) is an important mechanism for the precipitation of selenium from
      contaminated waters. Enzymatic reduction of Cr(VI) to the less mobile and less
      toxic Cr(III), and reduction of soluble Hg(II) to volatile Hg(O) may affect the
      fate of these compounds in the environment and might be used as a remediation
      strategy. Microorganisms can also enzymatically reduce other metals such as
      technetium, vanadium, molybdenum, gold, silver, and copper, but reduction of
      these metals has not been studied extensively.

PMID- 8257101
TI  - Regulation of sulfur and nitrogen metabolism in filamentous fungi.
AB  - In the filamentous fungi, N. crassa and A. nidulans, complex regulatory circuits
      control nitrogen metabolism and sulfur metabolism. The expression of entire sets
      of unlinked structural genes that encode metabolic enzymes is repressed when
      favored sulfur or nitrogen sources are available. These structural genes are
      coregulated by global positive-acting regulatory proteins and often are also
      controlled by metabolic inducers and pathway-specific regulatory proteins. The
      recent isolation of regulatory genes and representative structural genes of these
      circuits has provided significant new insight into the operation of both the
      nitrogen and the sulfur regulatory circuits, which involve sequence-specific DNA
      binding proteins, promoter control elements, metabolic inducers and repressors,
      and autogenous regulation.

PMID- 8257102
TI  - Molecular biology of hydrogen utilization in aerobic chemolithotrophs.
AB  - The aerobic bacteria capable of obtaining energy from the oxidation of H2 form a
      heterogenous group that includes both facultative and obligate chemolithotrophs
      and representatives of both gram-negative and gram-positive genera. H2-oxidizing
      aerobes inhabit such diverse biotypes as soil, oceans, and hot springs. The
      oxidation of H2 in these bacteria is catalyzed by [NiFe] metalloenzymes called
      hydrogenases. The hydrogenases studied so far belong to two families: dimeric,
      membrane-bound enzymes (MBH) coupled to electron transport chains and tetrameric,
      cytoplasmic NAD-reducing enzymes (SH). Ni2+ is an essential component of the
      active site contained in the large subunit of the MBH enzymes. The genes for the
      MBH enzymes are located in conserved clusters of accessory genes, some of which
      encode maturation functions and hydrogenase-related redox proteins. Maturation of
      both types of hydrogenase is apparently complex, involving specific nickel
      incorporation and proteolytic processing steps. In Alcaligenes eutrophus and
      Rhodobacter capsulatus, hydrogenase expression is regulated by transcriptional
      activators belonging to the response-regulator family.

PMID- 8257103
TI  - The surface trans-sialidase family of Trypanosoma cruzi.
AB  - Trypanosomes cannot synthesize sialic acids. Infectious stages of the life cycle
      of the human pathogen Trypanosoma cruzi express a cell-surface glycolipid
      anchored trans-sialidase, which can transfer sialic acid between glyco
      conjugates. Sialic acid is transferred from host cell-surface and serum
      sialylglycoproteins to trypanosome cell-surface glycoconjugates. The transfer
      reaction is specific for donors with terminal alpha-2,3-linked sialic acid, and
      terminal beta-1,4-linked galactose is the preferred acceptor. In the absence of
      an acceptor, the enzyme acts as a hydrolase, but cleavage is less efficient than
      transfer. Trans-sialidase activity is attributable to a few members of a large
      family of T. cruzi surface glycoproteins, many of which are simultaneously
      expressed. The functions of the trans-sialidase surface glycoprotein family are
      unknown but may be important for adhesion, invasion, virulence, or pathogenicity.
      A trans-sialidase is also expressed in the procyclic forms of Trypanosoma brucei.

PMID- 8257104
TI  - Trans-splicing of nematode premessenger RNA.
AB  - In nematodes, many mRNAs contain a common 5' terminal 22-nt sequence. This
      sequence, the spliced leader (SL), is acquired from a small (approximately 100
      nt) SL RNA via trans-splicing. Parallel in vitro and in vivo experiments have
      begun to clarify both the mechanism and biological role of trans-splicing. In
      vitro analysis (in cell free extracts) has shown that trans-splicing is
      remarkably similar to the snRNP mediated removal of intervening sequences from
      pre-mRNAs (cis-splicing). Additionally, this analysis has suggested a mechanism
      that may explain how the two substrates of trans-splicing (the SL RNA and pre
      mRNA) efficiently associate with one another in the absence of sequence
      complementarity. In vivo experiments suggest that a major biological function of
      trans-splicing in nematodes may be to process polycistronic transcription units.
      Results obtained from the study of both parasitic and free-living species are
      discussed, and trans-splicing in nematodes is compared and contrasted to the
      analogous process in trypanosomatid protozoans.

PMID- 8257105
TI  - Regulation of the phosphorelay and the initiation of sporulation in Bacillus
      subtilis.
AB  - The initiation of sporulation of bacteria is a complex cellular event controlled
      by an extensive network of regulatory proteins that serve to ensure that a cell
      embarks on this differentiation process only when appropriate conditions are met.
      The major signal-transduction pathway for the initiation of sporulation is the
      phosphorelay, which responds to environmental, cell cycle, and metabolic signals,
      and phosphorylates the Spo0A transcription factor activating its function. Signal
      input into the phosphorelay occurs through activation of kinases to phosphorylate
      a secondary-messenger protein, Spo0F. Spo0F-P serves as a substrate for
      phosphoprotein phosphotransferase, Spo0B, which phosphorylates Spo0A. The pathway
      is regulated by transcriptional control of its component proteins and by
      regulating phosphate flux through the pathway. This is accomplished by several
      regulatory proteins, and by activated Spo0A, which regulates transcription of
      genes for its own synthesis. Spo0A-P indirectly controls the transcription of
      numerous genes by regulating the level of other transcription regulators and
      directly activates the transcription of several regulatory proteins and sigma
      factors required for progression to the second stage of sporulation. Although the
      pathway and regulatory proteins have been identified, the signals and effectors
      for these regulators remain a mystery.

PMID- 8257107
TI  - Genetics and molecular biology of chitin synthesis in fungi.
AB  - In Saccharomyces cerevisiae, three chitin synthases have been detected. Chitin
      synthases I and II, the products of the CHS1 and CHS2 genes, respectively, are
      closely related proteins that require partial proteolysis for activity in vitro.
      In contrast, chitin synthase III is active in vitro without protease treatment,
      and three genes, CSD2 (= CAL1), CSD4 (= CAL2), and CAL3, are required for its
      activity. In the cell, the three enzymes have different functions. Chitin
      synthase I and II make only a small portion, < 10%, of the cellular chitin. In
      acidic media, chitin synthase I is required for normal budding. Chitin synthase
      II is required for normal morphology, septation, and cell separation. Chitin
      synthase III is required for the synthesis of 90% of the cellular chitin,
      including the chitin in the bud scars and lateral wall. Mutants defective in
      chitin synthase III are resistant to Calcofluor and Kluyveromyces lactis killer
      toxin, they lack alkali-insoluble glucan, and under certain circumstances, they
      are temperature-sensitive for growth. The available data suggest that many fungi
      have more than one chitin synthase and that these synthases are related to the S.
      cerevisiae CHS and CSD gene products.

PMID- 8257106
TI  - Adaptive mutation: the uses of adversity.
AB  - When populations of microorganisms are subjected to certain nonlethal selections,
      useful mutants arise among the nongrowing cells whereas useless mutants do not.
      This phenomenon, known as adaptive, directed, or selection-induced mutation,
      challenges the long-held belief that mutations only arise at random and without
      regard for utility. In recent years a growing number of studies have examined
      adaptive mutation in both bacteria and yeast. Although conflicts and
      controversies remain, the weight of the evidence indicates that adaptive mutation
      cannot be explained by trivial artifacts and that nondividing cells accumulate
      mutations in the absence of genomic replication. Because this process tends to
      produce only useful mutations, the cells appear to have a mechanism for
      preventing useless genetic changes from occurring or for eliminating them after
      they occur. The model that most readily explains the evidence is that cells under
      stress produce genetic variants continuously and at random, but these variants
      are immortalized as mutations only if they allow the cell to grow.

PMID- 8257108
TI  - Antibiotics synthesized by posttranslational modification.
AB  - Peptides that have antimicrobial activity are synthesized by many prokaryotic and
      eukaryotic organisms. Antimicrobial peptides commonly contain unusual amino acids
      that contribute to their properties and functions. Although bacteria synthesize
      most of these peptides by nonribosomal mechanisms, this review focuses on those
      that are synthesized by pathways that involve posttranslational modification of
      ribosomally synthesized precursor peptides. A particularly interesting class of
      these antimicrobial peptides is the lantibiotics, of which nisin and subtilin are
      the longest-known examples, although nearly a dozen new lantibiotics have been
      discovered in recent years. The fact that the lantibiotic structures are derived
      from gene-encoded peptides means that structural analogs of natural lantibiotics
      can be constructed by mutagenesis of their structural genes. Recent advances in
      our understanding of the molecular genetics of lantibiotics has made the
      construction of novel lantibiotics with enhanced chemical and antimicrobial
      properties possible. This review describes these advances and proposes future
      trends of research, as well as potential application of engineered lantibiotics,
      in the context of the general field of antimicrobial peptides.

PMID- 8257109
TI  - Agroactive compounds of microbial origin.
AB  - Microbial metabolites attract increasing attention as potential pesticides. They
      are expected to overcome the resistance and pollution that have accompanied the
      use of synthetic pesticides. Several microbial metabolites, such as avermectin,
      have proved useful as agroactive agents. In this review, we attempt to identify
      newer agroactive microbial metabolites with feasible activity or interesting
      action sites from those reported in recent years. In addition, microbial and
      chemical modifications of existing microbial agrochemicals are discussed to
      illustrate the usefulness of these technologies in potentiating agroactivity and
      stability. We discuss the possibility of future discovery of excellent microbial
      agrochemicals, and the importance of efforts to promote positive public
      perception and public acceptance of pesticide chemicals.

PMID- 8257110
TI  - Molecular biology of the LysR family of transcriptional regulators.
AB  - The LysR family is composed of > 50 similar-sized, autoregulatory transcriptional
      regulators (LTTRs) that apparently evolved from a distant ancestor into
      subfamilies found in diverse prokaryotic genera. In response to different
      coinducers, LTTRs activate divergent transcription of linked target genes or
      unlinked regulons encoding extremely diverse functions. Mutational studies and
      amino acid sequence similarities of LTTRs identify: (a) a DNA-binding domain
      employing a helix-turn-helix motif (residues 1-65), (b) domains involved in
      coinducer recognition and/or response (residues 100-173 and 196-206), (c) a
      domain required for both DNA binding and coinducer response (residues 227-253).
      DNA footprinting studies suggest that in the absence of coinducer many LTTRs bind
      to regulated promoters via a 15-bp dyadic sequence with a common structure and
      position (near -65). Coinducer causes additional interactions of LTTRs with
      sequences near the -35 RNA polymerase binding site and/or DNA bending that
      results in transcription activation.

PMID- 8257111
TI  - Enzymes and proteins from organisms that grow near and above 100 degrees C.
AB  - Microorganisms that can grow at and above 100 degrees C were discovered a decade
      ago, and about 20 different genera are now known. These so-called
      hyperthermophiles are the most ancient of all extant life; all but two genera are
      classified as Archaea. All have been isolated from geothermal heated environments
      including deep-sea hydrothermal vents. This group includes some methanogenic and
      sulfate-reducing species, but the majority are strictly anaerobic heterotrophs
      that utilize complex peptide mixtures as sources of energy, carbon, and nitrogen.
      Only a few species are saccharolytic. Most of the hyperthermophiles absolutely
      depend on the reduction of elemental sulfur (S0) to H2S for significant growth, a
      property that severely limits their large-scale culture in conventional
      fermentation systems. Consequently, most physiological and metabolic studies have
      focused on those that can also grow in the absence of S0, including species of
      the Archaea, Pyrococcus and Thermococcus, and the bacterium Thermotoga. The
      fermentative pathways for the metabolism of both peptides and carbohydrates in
      the Archaea appear to depend upon enzymes that contain tungsten, an element
      seldom used in biological systems. The mechanisms of S0 reduction and energy
      conservation remain unclear. Enzymes purified from the S0-reducing
      hyperthermophiles include proteases, amylolytic-type enzymes, hydrogenases, redox
      proteins, various ferredoxin-linked oxidoreductases, dehydrogenases, and DNA
      polymerases, some of which are active up to 140 degrees C. However, complete
      amino acid sequences are known for only a handful of these proteins, and the
      three-dimensional structure of only one hyperthermophilic protein has been
      determined. Potential mechanisms by which proteins and various biological
      cofactors and organic intermediates are stabilized at extreme temperatures are
      only now beginning to emerge.

PMID- 8257112
TI  - Genetics for all bacteria.
AB  - The availability of genetic analysis has now been extended to a wide variety of
      bacteria. While the traditional methods of conjugation, transduction, and
      transformation have made major contributions to microbiology and genetics, new
      recombinant DNA techniques and the development of new equipment for
      characterization and isolation of DNA fragments have enabled genome analysis of
      many bacteria for which no genetic information was previously available. These
      new procedures have enabled the construction of detailed physical/genetic maps as
      well as precise measurements of genome size, and provided new data on functional
      arrangements of genes in the bacterial genome. Such information is proving
      increasingly valuable for many aspects of microbiology as well as for the genetic
      manipulation of bacteria important in human disease, agriculture, and
      biotechnology.

PMID- 8257113
TI  - Evaluating bioremediation: distinguishing fact from fiction.
AB  - Bioremediation options encompass diverse types of biochemical mechanisms that may
      lead to a target's mineralization, partial transformation, humification, or
      altered redox state (e.g. for metallic elements). Because these various
      mechanisms produce alternative fates of the targeted pollutants, it is often
      necessary to use diverse evaluation criteria to qualify a successful
      bioremediation. Too often target depletion from a treated matrix can be
      mistakenly ascribed to biological activity when in fact the depletion is caused
      by abiotic losses (e.g. volatilization, leaching, and stripping). Thus,
      effective, and therefore convincing, evaluation requires that experimental and
      engineering designs anticipate all possible routes of target depletion and that
      these routes be carefully monitored.

PMID- 8257114
TI  - Genetically engineered protection against viruses in transgenic plants.
AB  - Transgenic plants carrying nucleotide sequences derived from plant viruses can
      exhibit increased resistance to viral disease. Many viral sequences confer some
      level of either resistance to infection or suppression of disease symptoms
      (tolerance). These include segments of viral genomes encoding capsid or coat
      proteins, sequences encoding proteins that are or may be subunits of the viral
      replicase, sequences incapable of encoding proteins, entire genomes of defective
      interfering viruses and satellite viruses, and complete genomes of mild strains
      of virus. The transgene may act on initiation of infection, replication of virus,
      spread of the infection throughout the plant, and symptom development. More than
      one of these processes can be impaired by a single transgene derived from a
      single viral gene. The level of protection ranges from very low to high, while
      the breadth of protection ranges from very narrow, where protection is only
      observed against closely related strains of the virus from which the transgene
      was derived, to moderately broad, extending to other viruses. Data are
      insufficient to establish a molecular mechanism of resistance for most of the
      described examples. In addition, although the use of a particular segment of the
      viral genome confers resistance in one virus-host system, analogous sequences
      from a different virus in another host may be ineffective.

PMID- 8257115
TI  - Genetic manipulation of negative-strand RNA virus genomes.
AB  - Negative-strand RNA viruses have been refractory to genetic manipulation using
      recombinant DNA techniques. Recently, new techniques were developed that allowed
      the rescue of synthetic RNA molecules into influenza A viruses and, subsequently,
      into other negative-strand RNA viruses. These techniques are presently being used
      to study the molecular biology of these viruses. Questions concerning cis- and
      trans-acting elements that are involved in transcription and replication of
      negative-sense RNA viral genomes can now be addressed with reverse genetic
      approaches. Further development of this methodology has enabled the construction-
      by recombinant DNA techniques--of influenza A viruses that contain altered
      genomes. The phenotypic characteristics and possible applications of these novel
      transfectant viruses are also discussed.

PMID- 8257116
TI  - The cellulosome: the exocellular organelle of Clostridium.
AB  - The cellulolytic enzyme complex of the anaerobic thermophile Clostridium
      thermocellum is reviewed. This complex, called the cellulosome, is cell
      associated and has a mass of from 2 x 10(6) to 6.5 x 10(6) Daltons. It consists
      of from 14 to 26 different polypeptides. Cellulosomes form larger complexes,
      polycellulosomes, with masses from 50 x 10(6) to 80 x 10(6) Daltons. The
      cellulosome efficiently hydrolyzes crystalline cellulose whereas individual
      polypeptides alone or in mixtures do not. Many of the polypeptides are
      catalytically active and can be characterized as endoglucanases, xylanases, and
      cellodextrinases. Several of the polypeptides have been sequenced including the
      largest subunit, CipA, that is a glycoprotein with a mass of 210 kDa. CipA has a
      cellulose-binding domain and nine internal repeated sequences postulated to bind
      eight catalytic subunits and a special peptide (ORF3p). The ORF3p anchors the
      CipA to the cell surface. CipA can be characterized as a scaffold holding the
      catalytic subunits that line up with the cellulose fiber. This arrangement allows
      a multiple cutting of the cellulose glucan chain. A similar system has been
      observed for other cellulosome-like complexes, notably Clostridium cellulovorans.

PMID- 8257117
TI  - The proteases and pathogenicity of parasitic protozoa.
AB  - Protozoan parasites are among the most prevalent pathogens worldwide. Diseases
      like malaria, leishmaniasis, amebiasis, and trypanosomiasis affect hundreds of
      millions of people. Recent advances in our understanding of the biochemistry and
      molecular biology of these organisms has focused attention on specific parasite
      molecules that are key to the parasite life cycle or the pathogenesis of the
      diseases they produce. One group of enzymes that plays myriad roles in these
      processes are the parasite-derived proteases. Different types of proteases are
      frequently expressed at different stages of the parasite life cycle to support
      parasite replication and metamorphosis. Intracellular parasites such as those
      that produce malaria and Chagas' disease express high levels of protease activity
      to efficiently degrade host proteins like hemoglobin. In other instances, such as
      infection with Entamoeba histolytica, the causative agent of amebiasis, proteases
      released by the parasite can damage host cells and tissues, contributing to host
      tissue damage and parasite invasion. Detailed studies of these enzymes have led
      to model systems for the study of parasite gene regulation, parasite metabolism,
      and the host-parasite interplay. In some instances, proteases appear to be
      promising targets for the development of new antiparasitic chemotherapy.

PMID- 8257118
TI  - The stationary phase of the bacterial life cycle.
AB  - In the natural environment bacteria seldom encounter conditions that permit
      periods of exponential growth. Rather, bacterial growth is characterized by long
      periods of nutritional deprivation punctuated by short periods that allow fast
      growth, a feature that is commonly referred to as the feast-or-famine lifestyle.
      In this chapter we review the recent advances made in our understanding of the
      molecular events that allow some gram-negative bacteria to survive prolonged
      periods of starvation. After an introductory description of the properties of
      starved gram-negative bacteria, the review presents three aspects of stationary
      phase: entry into stationary phase, responses during prolonged starvation, and
      reentry into the growth cycle.

PMID- 8257119
TI  - Polyketide synthesis: prospects for hybrid antibiotics.
AB  - Polyketides fall into two structural classes: aromatic and complex. The former
      are built mainly from acetate units through a reiterative process wherein the
      beta-carbonyl groups formed after each condensation cycle are left largely
      unreduced. Complex polyketides are composed of acetates, propionates, or
      butyrates, and the extent of beta-carbonyl reduction varies from one cycle to the
      next. Two themes for polyketide synthases are emerging. Aromatic PKSs are
      determined by four to six genes encoding mono- or bifunctional enzymes; one PKS
      complex is used for all synthesis steps. Complex PKSs are composed of several
      multifunctional polypeptides that contain enzymatic domains for the condensation
      and reduction steps; each domain is used at a unique step in the pathways, and
      the extent of beta-carbonyl processing depends on the functional domains
      operating at that cycle. Mutations rendering certain domains nonfunctional have
      been introduced into genes for complex polyketides, resulting in the production
      of novel molecules.

PMID- 8257120
TI  - Release of recombinant microorganisms.
AB  - This review addresses current environmental applications of naturally occurring,
      nonrecombinant microorganisms and potential future genetic modifications of such
      organisms, as well as releases of recombinant microorganisms that have occurred
      to date. Awareness of the current uses of nonrecombinant microorganisms provides
      insight into the diversity of habitats in which recombinant microorganisms may be
      released in the future, while an examination of potential and realized genetic
      modifications provides insight into the variety of applications for which
      recombinant microorganisms may be used. Analysis of the behavior, persistence,
      and dispersal of nonrecombinant strains further provides valuable information
      required for the assessment of the risk involved in release of recombinant
      derivatives of those strains. Approximately 27 distinct releases of recombinant
      microorganisms have occurred to date. This review assesses what has been learned
      from such releases regarding persistence, dispersal, and potential deleterious
      environmental effects.

PMID- 8257122
TI  - Direct, automated detection of rifampin-resistant Mycobacterium tuberculosis by
      polymerase chain reaction and single-strand conformation polymorphism analysis.
AB  - A rapid screening test was recently established for the detection of mutations in
      the rpoB gene of Mycobacterium tuberculosis, a region identified as the locus for
      rifampin resistance (Rifr). The detection method involved the amplification by
      polymerase chain reaction (PCR) of the Rifr region and the identification of
      mutations by single-strand DNA conformation polymorphism analysis (SSCP) of the
      amplification products. Experience using two different PCR-SSCP formats for the
      evaluation of BACTEC cultures and sputum is presented here; the previously
      described manual procedure for the detection for the detection of radiolabelled
      amplification products and an automated SSCP by which fluorescein-labelled
      products were detected on a Pharmacia DNA sequencer apparatus. All 17 different
      Rifr mutations known to date were consistently detected. PCR-SSCP could be used
      for the evaluation of minimally grown cultures (BACTEC 12B medium with a growth
      index of < or = 100) and for direct screening of microscopically positive sputa
      with greater than 10 organisms per field (magnification, x250). Implementation of
      this technique could result in rapid detection of rifampin resistance in M.
      tuberculosis, a marker of multidrug-resistant tuberculosis.

PMID- 8257123
TI  - Characterization of a new TEM-type beta-lactamase resistant to clavulanate,
      sulbactam, and tazobactam in a clinical isolate of Escherichia coli.
AB  - A clinical Escherichia coli strain highly resistant to the combinations of
      amoxicillin-clavulanate, ampicillin-sulbactam, and piperacillin-tazobactam was
      isolated from a patient with a community-acquired urinary tract infection who was
      previously treated with amoxicillin-clavulanate. These resistances were carried
      by a 45-kb conjugative plasmid encoding for a single beta-lactamase with a pI of
      5.4. Cloning and sequencing of the new beta-lactamase, IRT-3, revealed identity
      with the blaT1 gene encoding the TEM-1 beta-lactamase except for a replacement of
      the methionine residue at position 67 by isoleucine and of the methionine residue
      at position 180 by threonine. Both mutations were segregated by the construction
      of hybrid genes, and only the mutation at methionine at position 67 was related
      to resistance to the suicide inhibitors. The inhibitory effects of clavulanate,
      sulbactam, and tazobactam on the TEM-1 enzyme were substantially decreased in
      comparison with those on IRT-3, as indicated by the 50% inhibitory
      concentrations.

PMID- 8257121
TI  - Penicillin-binding proteins and bacterial resistance to beta-lactams.

PMID- 8257124
TI  - Treatment of tinea unguium with medium and high doses of ultramicrosize
      griseofulvin compared with that with itraconazole.
AB  - Toenail tinea is a very recalcitrant dermatosis. Griseofulvin at > or = 500
      mg/day is the current medication of choice, but it is minimally successful. In a
      controlled open trial ultramicrosize griseofulvin (UMSG) at doses of 660 and 990
      mg/day was compared with itraconazole at 100 mg/day in 109 patients. At 4-week
      intervals, the patients were evaluated for their clinical and mycological
      statuses and adverse reactions. Treatment was given for up to 18 months.
      Compliance was checked by tablet counting. Response (cure, partial cure, marked
      improvement) was analyzed by the intent-to-treat method. Cured and partially
      cured patients were followed up. Except for one early dropout, the toenails
      (mean, 6 to 7) were involved. Cure or partial cure was found in 6% (UMSG at 660
      mg), 14% (UMSG at 990 mg), and 19% (itraconazole at 100 mg) of patients (P =
      0.2097); marked improvement was found in 36, 44, and 39% of patients in the three
      treatment groups, respectively. Most patients had to be treated for 18 months.
      Failure was related to short medication periods (adverse drug reactions,
      dropout). While stable cure was not obtained with UMSG at 660 mg, the higher dose
      of UMSG and itraconazole gave stable cures in the other patients. Side effects of
      nausea, diarrhea, and headache were found in 20, 26, and 11 patients,
      respectively (P = 0.0028), and the numbers in whom medication had to be
      discontinued differed, too (P = 0.0137). While there was no major difference with
      glutamic-pyruvic transaminase and gamma-GT, total and low-density lipoprotein
      cholesterol levels declined slightly in the itraconazole group (P = 0.0357 and P
      = 0.0639, respectively, at 3 months). More than 70% of the patients had an
      average compliance of > or = 90%; four patients (two dropouts) were poor
      compliers. In conclusion, it appears questionable whether griseofulvin can
      continue to be considered the "gold standard" in the treatment of toenail tinea.
      At present, itraconazole at 100 mg shows better efficacy and is better tolerated.

PMID- 8257125
TI  - Antibiotic treatment of experimental endocarditis due to vancomycin- and
      ampicillin-resistant Enterococcus faecium.
AB  - We compared ciprofloxacin, rifampin, and gentamicin treatments, alone and in
      combination, for 5 days in the therapy of experimental aortic valve endocarditis
      in rats caused by a clinical isolate of vancomycin-resistant Enterococcus
      faecium. The MICs and MBCs of vancomycin, ciprofloxacin, rifampin, and gentamicin
      were 250 and > 1,000, 3.1 and 6.3, 0.098 and 1.6, and 12.5 and > 50
      micrograms/ml, respectively. Infected rats were sacrificed after completing 5
      days of therapy. Additional rats within each treatment group were followed for 5
      days beyond the last dose of antibiotic therapy. Although survivals in the
      different groups were not significantly different after 5 days of therapy,
      survival was significantly better 5 days beyond the last dose of antibiotic
      therapy in rats treated with rifampin-containing regimens. The combination of
      ciprofloxacin and gentamicin was bactericidal in vitro and in vegetations from
      rats with enterococcal endocarditis. Rifampin alone was similarly bactericidal in
      vivo, but it was not significantly better than rifampin in combination with other
      antibiotics. Subpopulations resistant to rifampin, but not ciprofloxacin, were
      detected in the inoculum and in most vegetations during therapy. However, the
      combination of ciprofloxacin plus both gentamicin and rifampin reduced both the
      rifampin-susceptible and -resistant population in vegetations of 9 of 10 animals
      below the level of detection after 5 days of therapy. Nevertheless, a residual
      enterococcal population apparently remained in numbers of < 2 log10 CFU/g after 5
      days of therapy, which resulted in relapse. Perhaps a longer course of therapy
      would have eliminated this residual population and improved efficacy.

PMID- 8257126
TI  - Analysis of the aac(3)-VIa gene encoding a novel 3-N-acetyltransferase.
AB  - Biochemical analysis (G. A. Papanicolaou, R. S. Hare, R. Mierzwa, and G. H.
      Miller, abstr. 152, Program Abstr. 29th Intersci. Conf. Antimicrob. Agents
      Chemother., 1989) demonstrated the presence of a novel 3-N-acetyltransferase in
      Enterobacter cloacae 88020217. This organism was resistant to gentamicin, and the
      MIC of 2'-N-ethylnetilmicin for it was fourfold lower than that of 6'-N
      ethylnetilmicin, a resistance pattern which suggested 2'-acetylating activity.
      However, high-pressure liquid chromatography analysis demonstrated that the
      enzyme acetylated sisomicin in the 3 position. We have cloned the structural gene
      for this enzyme from a large (> 70-kb) conjugative plasmid present in E. cloacae.
      Subcloning experiments have localized the aac(3)-VIa gene to a 2.1-kb Sau3A
      fragment. The deduced AAC(3)-VIa protein showed 48% amino acid identity to the
      AAC(3)-IIa protein and 39% identity to the AAC(3)-VII protein. Examination of the
      5'-flanking sequences demonstrated that the aac(3)-VIa gene was located 167 bp
      downstream of the aadA1 gene and was present in an integron. In addition, the
      aac(3)-VIa gene is also downstream of a 59-base element often seen in an integron
      environment. Primer extension analysis has identified a promoter for the aac(3)
      VIa gene downstream of both the aadA1 gene and a 59-base element.

PMID- 8257127
TI  - Erythromycin, clarithromycin, and azithromycin: use of frequency distribution
      curves, scattergrams, and regression analyses to compare in vitro activities and
      describe cross-resistance.
AB  - MICs of erythromycin, clarithromycin, and azithromycin for 852 recent clinical
      isolates were determined by broth microdilution methods. Frequency distribution
      curves, scattergrams, and regression analyses were used to compare in vitro
      activities and describe cross-resistance. Clarithromycin was the most active drug
      against Bacteroides spp. but the least active against Haemophilus influenzae.
      Azithromycin was most active against H. influenzae, Moraxella catarrhalis,
      Pasteurella multocida, and Fusobacterium spp. but the least active against
      Streptococcus spp. and Enterococcus spp. All three drugs had equivalent
      activities against Staphylococcus spp. and gram-positive anaerobes. None of the
      three drugs was particularly active against members of the family
      Enterobacteriaceae or nonfermentative gram-negative bacilli, although
      concentrations of 4 micrograms of azithromycin per ml inhibited some strains of
      the family Enterobacteriaceae (particularly Escherichia coli and Citrobacter
      diversus) and Acinetobacter baumannii. Although relative drug activities varied
      by organism, organisms relatively susceptible to one were relatively susceptible
      to all and organisms relatively resistant to one were relatively resistant to
      all; an exception was fusobacteria, which were usually susceptible only to
      azithromycin. Cross-susceptibility and cross-resistance were, therefore, the rule
      (except for Fusobacterium spp.), although the percentage of susceptible organisms
      could be varied considerably on the basis of the selection of breakpoints.

PMID- 8257128
TI  - CGP 53437, an orally bioavailable inhibitor of human immunodeficiency virus type
      1 protease with potent antiviral activity.
AB  - CGP 53437 is a peptidomimetic inhibitor of human immunodeficiency virus type 1
      (HIV-1) protease containing a hydroxyethylene isostere. The compound inhibited
      recombinant HIV-1 protease with a Ki of 0.2 nM. The inhibition constant versus
      human cathepsin D and human cathepsin E was 4 nM. Human pepsin and gastricsin
      were inhibited with Kis of 8 and 500 nM, respectively, and human renin was
      inhibited with a Ki of 190 microM. The replication of HIV-1/LAV, HIV-1/Z-84, and
      HIV-1/pLAI was inhibited with a 90% effective dose of 0.1 microM in acutely
      infected MT-2 cells. The 50% cytotoxic dose was 100 microM. Similar antiviral
      activity was observed when the compound was added up to 10 h after infection. At
      the effective concentration, processing of Gag precursor protein p55 was greatly
      reduced, confirming an action on the late stage of the virus life cycle, as
      expected. The efficacy of the inhibitor was also demonstrated by using primary
      human peripheral blood lymphocytes infected with the HIV-1/LAV strain, low
      passage clinical isolates obtained from HIV-1-seropositive individuals (including
      a zidovudine-resistant strain), and HIV-2/ROD. In these cells, CGP 53437 delayed
      the onset of HIV replication in a dose-dependent fashion (substantial effects
      with concentrations of > or = 0.1 microM) as long as the inhibitor was maintained
      in the culture. CGP 53437 was orally bioavailable in mice. Concentrations in
      plasma 10-fold in excess of the in vitro antiviral 90% effective dose could be
      sustained for several hours after oral application of 120 mg/kg. Therefore, CGP
      53437 has the potential to be a therapeutically useful anti-HIV agent for the
      treatment of AIDS.

PMID- 8257129
TI  - Characterization of Acinetobacter haemolyticus aac(6')-Ig gene encoding an
      aminoglycoside 6'-N-acetyltransferase which modifies amikacin.
AB  - The amikacin resistance gene acc(6')-Ig of Acinetobacter haemolyticus BM2685
      encoding an aminoglycoside 6'-N-acetyltransferase was characterized. The gene was
      identified as a coding sequence of 438 bp corresponding to a protein with a
      calculated mass of 16,522 Da. Analysis of the deduced amino acid sequence
      suggested that it was the fourth member of a subfamily of aminoglycoside 6'-N
      acetyltransferases. The resistance gene was not transferable either by
      conjugation to Escherichia coli or to Acinetobacter baumannii or by
      transformation into Acinetobacter calcoaceticus. Plasmid DNA from strain BM2685
      did not hybridize with an intragenic aac(6')-Ig probe. These results suggest a
      chromosomal location for this gene. The gene was detected by DNA hybridization in
      all 20 strains of A. haemolyticus tested but not in 179 other Acinetobacter
      strains, including A. baumannii, A. lwoffii, A. junii, and A. johnsonii and
      genospecies 3, 6, 11, 13, 14, 15, 16, and 17, of which 162 were amikacin
      resistant. The probe did not hybridize in dot blot assays with DNAs purified from
      members of the families Enterobacteriaceae and Pseudomonadaceae that encode 6'-N
      acetyltransferases. These data suggest that the aac(6')-Ig gene is species
      specific and may be used to identify A. haemolyticus.

PMID- 8257130
TI  - Effects of itraconazole on cytochrome P-450-dependent sterol 14 alpha
      demethylation and reduction of 3-ketosteroids in Cryptococcus neoformans.
AB  - As in other pathogenic fungi, the major sterol synthesized by Cryptococcus
      neoformans var. neoformans is ergosterol. This yeast also shares with most
      pathogenic fungi a susceptibility of its cytochrome P-450-dependent ergosterol
      synthesis to nanomolar concentrations of itraconazole. Fifty percent inhibition
      of ergosterol synthesis was reached after 16 h of growth in the presence of 6.0
      +/- 4.7 nM itraconazole, and complete inhibition was reached at approximately 100
      nM itraconazole. This inhibition coincided with the accumulation of mainly
      eburicol and the 3-ketosteroid obtusifolione. The radioactivity incorporated from
      [14C]acetate in both compounds represents 64.2% +/- 12.9% of the radioactivity
      incorporated into the sterols plus squalene extracted from cells incubated in the
      presence of 10 nM itraconazole. The accumulation of obtusifolione as well as
      eburicol indicates that itraconazole inhibits not only the 14 alpha-demethylase
      but also (directly or indirectly) the NADPH-dependent 3-ketosteroid reductase,
      i.e., the enzyme catalyzing the last step in the demethylation at C-4. This
      latter inhibition obviates the synthesis of 4,4-demethylated 14 alpha
      methylsterols that may function at least partly as surrogates of ergosterol.
      Eburicol and obtusifolione are unable to support cell growth, and the 3
      ketosteroid has been shown to disturb membranes. The complete inhibition of
      ergosterol synthesis and the accumulation of the 4,4,14-trimethylsterol and of
      the 3-ketosteroid together with the absence of sterols, such as 14 alpha
      methylfecosterol and lanosterol, which can partly fulfill some functions of
      ergosterol, are at the origin of the high activity of itraconazole against C.
      neoformans. Fifty percent inhibition of growth achieved after 16 h of incubation
      in the presence of 3.2 +/- 2.6 nM itraconazole.

PMID- 8257131
TI  - Effects of cardiopulmonary bypass surgery on intravenous ciprofloxacin
      disposition.
AB  - The pharmacokinetic parameters of intravenous ciprofloxacin were examined in five
      adult male patients on three separate occasions of open heart surgery: the 24 h
      before cardiopulmonary bypass (CPB) surgery, (PRE), during surgery (SURG), and 48
      to 72 h after surgery (POST). Serial blood (n = 16), urine, and SURG tissue
      samples were collected after intravenous administration of a single 300-mg dose
      of ciprofloxacin during each study period. All samples were assayed for
      ciprofloxacin by a specific high-performance liquid chromatographic method. Serum
      ciprofloxacin concentrations remained constant or continued to decline during the
      course of CPB surgery. A significant (P < 0.05) decrease in total body clearance
      was observed during the SURG and POST phases (298 and 306 ml/min/1.73 m2,
      respectively) compared with that during the PRE phase (364 ml/min/1.73 m2). Renal
      clearances and elimination half-lives were similar during all three study phases.
      A nonsignificant decline occurred in the apparent volume of distribution, from
      mean values of 2.1 and 2.0 liters/kg during the PRE and POST phases,
      respectively, to 1.7 liters/kg during the SURG phase. The mediastinal fat tissue
      ciprofloxacin concentrations ranged from 0.45 to 2.89 micrograms/g. Overall,
      little significant difference was noted in the disposition of intravenous
      ciprofloxacin during CPB surgery compared with that before and after surgery.

PMID- 8257132
TI  - Antimicrobial activity of DV-7751a, a new fluoroquinolone.
AB  - We compared the in vitro antibacterial activity of DV-7751a against gram-positive
      and -negative bacteria with those of quinolones currently available. MICs for 90%
      of the strains tested (MIC90s) against clinical isolates of methicillin
      susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis
      were 0.20, 0.39, 0.20, and 0.78 micrograms/ml, respectively. Moreover, MIC50s for
      DV-7751a against ofloxacin-resistant methicillin-resistant S. aureus were 4-, 8-,
      16-, 32-, and 64-fold lower than those for tosufloxacin and sparfloxacin,
      levofloxacin, ofloxacin and fleroxacin, ciprofloxacin, and lomefloxacin,
      respectively. DV-7751a inhibited the growth of all strains of Streptococcus
      pneumoniae, Streptococcus pyogenes, and Peptostreptococcus spp. at 0.39, 0.39,
      and 0.78 micrograms/ml, respectively, and was 4- to > 16-fold more active against
      enterococci at the MIC90 level than the other quinolones tested. The activity of
      DV-7751a against Pseudomonas aeruginosa was roughly comparable to those of
      levofloxacin and sparfloxacin at the MIC90 level and was two- to fourfold less
      than that of ciprofloxacin. DV-7751a showed activity comparable to those of
      levofloxacin and ciprofloxacin against the other glucose-nonfermenting bacteria
      Haemophilus influenzae, Neisseria gonorrhoeae, and Moraxella catarrhalis (MIC90s
      of 0.025, 0.20, and 0.10 micrograms/ml, respectively). DV-7751a activity was not
      affected by medium, inoculum size, or the addition of human serum but was
      decreased under acidic conditions and in human urine, as were the other
      quinolones tested. Time-kill curve studies demonstrated the rapid bactericidal
      action of DV-7751a against S. aureus, S. pneumoniae, Escherichia coli, and P.
      aeruginosa. The frequency of spontaneous resistance to DV-7751a was less than or
      equal to those of the reference drugs. DV-7751a inhibited the supercoiling
      activity of DNA gyrases from S. aureus, E. coli, and P. aeruginosa at
      concentrations comparable to those of levofloxacin and sparfloxacin.

PMID- 8257133
TI  - Identification of the satA gene encoding a streptogramin A acetyltransferase in
      Enterococcus faecium BM4145.
AB  - Enterococcus faecium BM4145, a clinical isolate from urine, was resistant to
      streptogramin group A antibiotics by inactivation. The strain harbored a plasmid
      containing a gene, satA, responsible for this resistance; this gene was cloned
      and sequenced. It encoded SatA, a protein deduced to be 23,634 Da in mass and
      homologous with a new family of chloramphenicol acetyltransferases described in
      Agrobacterium tumefaciens, Escherichia coli, Pseudomonas aeruginosa, and
      Staphylococcus aureus. The similarity of SatA to other acetyltransferases, LacA
      (thiogalactoside acetyltransferase) and CysE (serine acetyltransferase) from E.
      coli, and to two putative acetyltransferases, NodL from Rhizobium leguminosarum
      and Urf1 from E. coli, was also observed in a region considered to be the
      enzyme's active site. Acetylation experiments indicated that acetyl coenzyme A
      was necessary for SatA activity and that a single acetylated derivative of
      pristinamycin IIA was produced. Other members of the streptogramin A group such
      as virginiamycin M and RP54476 were also substrates for the enzyme. We conclude
      that resistance to the streptogramin A group of antibiotics in E. faecium BM4145
      is due to acetylation by an enzyme related to the novel chloramphenicol
      acetyltransferase family.

PMID- 8257134
TI  - In vitro studies of a new antifungal triazole, D0870, against Candida albicans,
      Cryptococcus neoformans, and other pathogenic yeasts.
AB  - We investigated the effects of various assay conditions on the activity of D0870
      against seven species of fungi in the broth macrodilution testing procedure
      proposed by the National Committee for Clinical Laboratory Standards (NCCLS).
      Multivariate analysis demonstrated that endpoint definition, starting inoculum
      size, medium composition, type of buffer, and length of incubation, but not pH or
      temperature, had significant effects on results. Increasing the inoculum from
      10(2) to 10(5) yeast cells/ml raised the MICs for all isolates up to > 75,000
      fold. This effect was greatest when endpoints corresponded to a 90% reduction in
      visually determined turbidity (MIC90), was less prominent with an 80% inhibition
      visual endpoint (MIC80), and was nearly absent with a 50% endpoint measured by a
      spectrophotometer (IC1/2). Differences due to medium composition were
      attributable to antibiotic medium 3 with RPMI and yeast nitrogen base media
      performing nearly identically. Under standardized conditions as specified in
      NCCLS document M27-P (Reference Method for Broth Dilution Antifungal
      Susceptibility Testing of Yeasts; Proposed Standard, 1992), 79 strains (5 to 25
      strains for each species) demonstrated median MIC80s of 0.0037 and 0.0075
      microgram/ml for Candida albicans and Cryptococcus neoformans, respectively. In
      contrast, Candida krusei and Torulopsis glabrata had a median MIC80 of 1.0
      microgram/ml. Our studies indicate that the pathogenic yeasts C. albicans and C.
      neoformans are more susceptible to D0870 than other pathogenic yeasts.

PMID- 8257135
TI  - Influence of rifampin on fleroxacin pharmacokinetics.
AB  - Staphylococcus aureus infections have been successfully treated in animal models
      with the combination of fleroxacin and rifampin. We studied the influence of
      rifampin, a potent cytochrome P-450 inducer, on the pharmacokinetics and
      biotransformation of fleroxacin in 14 healthy young male volunteers. Subjects
      were given 400 mg of fleroxacin orally once a day for 3 days to reach steady
      state. After a wash-out period of 2 days, the same subjects received 600 mg of
      rifampin orally once daily for 7 days. On days 5 to 7 of rifampin treatment, 400
      mg of fleroxacin was again administered once daily. Concentrations of fleroxacin
      as well as its two major urinary metabolites, N-demethyl- and N-oxide-fleroxacin,
      in plasma and urine were determined by reverse-phase high-performance liquid
      chromatography. The extent of hepatic enzyme induction by rifampin was confirmed
      by a significant increase of 6-beta-hydroxycortisol urinary output from 160.8 +/-
      41.4 to 544.8 +/- 120.7 micrograms/4 h. There were no significant changes in the
      peak fleroxacin concentration in plasma (6.3 +/- 1.2 versus 6.2 +/- 1.9
      mg/liter), time to maximum concentration of fleroxacin in plasma (1.1 +/- 0.9
      versus 1.3 +/- 1.1 h), or renal clearance (58.3 +/- 16.4 versus 61.9 +/- 19.2
      ml/min). The area under the curve AUC (71.4 +/- 15.8 versus 62.2 +/- 13.7
      mg.h/liter) and the terminal half-life of fleroxacin (11.4 +/- 2.2 versus 9.2 +/-
      1.1 h) decreased (P < 0.05), while the total plasma clearance increased from 97.7
      +/- 21.6 to 112.3 +/- 25.8 ml/min (P < 0.01). Despite being statistically
      significant, this 15% increase in total plasma clearance does not appear to be
      clinically relevant. Metabolic clearance by N demethylation was increased ( 6.9
      +/- 2.4 versus 12.5 +/- 3.2 ml/min; P < 0.01), whereas clearance by N oxidation
      did not change (5.8 +/- 1.1 versus 5.8 +/- 1.5 ml/min). Fleroxacin elimination
      was slightly increased (about 15%) through induction of metabolic clearance to N
      demethyl-fleroxacin. Since fleroxacin levels remained above the MIC for 90% of
      the tested isolates of methicillin-susceptible S. aureus for at least 24 h, dose
      adjustment does not appear necessary, at least for short-term treatments.

PMID- 8257136
TI  - Vancomycin skin tests and prediction of "red man syndrome" in healthy volunteers.
AB  - The purpose of the present study was to assess the cutaneous response to
      intradermally administered vancomycin in healthy adults and to determine whether
      the magnitude of the cutaneous response correlated to the severity of "red man
      syndrome" (RMS) following intravenous administration of vancomycin to the same
      subjects. Eleven healthy males were skin tested with intradermally administered
      histamine and saline controls and intradermally administered vancomycin at
      different concentrations. Vancomycin caused a dose-dependent area of flare in all
      subjects. The sigmoidal maximal flare model was used to fit each dose-response
      curve, and cutaneous responsiveness to vancomycin was quantified by various
      methods, including the flare area at each dose, maximum flare area (maximal
      flare), dose required to produce 50% of maximum flare, dose required to produce a
      flare area of 400 mm2, and the slope of the dose-response curve. One week after
      skin testing, subjects received an infusion of vancomycin, 15 mg/kg of body
      weight over 60 min. For the assessment of the severity of RMS, we used previously
      described methods. Although all subjects experienced erythema from the
      intravenously administered vancomycin and 10 subjects had pruritus, there was no
      significant correlation between vancomycin skin test results and the severity of
      RMS. We conclude that vancomycin skin tests do not predict the severity of RMS.
      In addition, vancomycin skin tests may be of no benefit for assessing
      immunoglobulin E-mediated allergy to vancomycin, since all subjects had a
      positive reaction at concentrations of > or = 10 micrograms/ml.

PMID- 8257137
TI  - Pharmacokinetics of [18F]fleroxacin in healthy human subjects studied by using
      positron emission tomography.
AB  - Positron emission tomography (PET) with [18F]fleroxacin was used to study the
      pharmacokinetics of fleroxacin, a new broad-spectrum fluoroquinolone, in 12
      healthy volunteers (9 men and 3 women). The subjects were infused with a standard
      therapeutic dose of fleroxacin (400 mg) supplemented with approximately 20 mCi of
      [18F]fleroxacin. Serial PET images were made and blood samples were collected for
      8 h, starting at the initiation of the infusion. The subjects were then treated
      with unlabeled drug for 3 days (400 mg/day). On the fifth day, infusion of
      radiolabeled drug, PET imaging, and blood collection were repeated. In most
      organs, there was rapid accumulation of radiolabeled drug, with stable levels
      achieved within 1 h after completion of the infusion. Especially high peak
      concentrations (in micrograms per gram) were achieved in the kidney (> 34), liver
      (> 25), lung (> 20), myocardium (> 19), and spleen (> 18). Peak concentrations of
      drug more than two times the MIC for 90% of Enterobacteriaceae strains tested (>
      10-fold for most organisms) were achieved in all tissues except the brain and
      remained above this level for more than 6 to 8 h. The plateau concentrations in
      tissues (2 to 8 h, in micrograms per gram +/- standard error of the mean) of drug
      were as follows: brain, 0.83 +/- 0.032; myocardium, 4.53 +/- 0.24; lung, 5.80 +/-
      0.48; liver, 7.31 +/- 0.33; spleen, 6.00 +/- 0.47; bowel, 3.53 +/- 0.74; kidney,
      8.85 +/- 0.64; bone, 2.87 +/- 0.29; muscle, 4.60 +/- 0.33; prostate, 4.65 +/-
      0.48; uterus, 3.87 +/- 0.39; breast, 2.68 +/- 0.11; and blood, 2.35 +/- 0.09.
      Concentrations of fleroxacin in tissue were similar in males and females, before
      and after pretreatment with unlabeled drug.

PMID- 8257138
TI  - Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients
      with AIDS.
AB  - The influence of a standard breakfast on the single-dose pharmacokinetics of
      zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied
      in 27 subjects with advanced human immunodeficiency virus infection (Centers for
      Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide
      metabolite (GAZT) in serum and urine were measured by a high-pressure liquid
      chromatographic method. Pharmacokinetic analysis was done by an open one
      compartment model as well as noncompartmentally. The results were summarized as
      medians with 50% confidence ranges because of the high degree of interindividual
      variability. Peak levels in plasma were moderately reduced after administration
      of 100 mg AZT in the nonfasting group (1.79 mumol/liter in the fasting group [F],
      1.12 mumol/liter in the group that received breakfast [B]) and were markedly
      reduced after administration of 250 mg AZT (6.51 mumol/liter [F], 1.79
      mumol/liter [B]). The terminal half-life in plasma was prolonged almost twofold
      after breakfast with 100 and 250 mg of AZT (100 mg, 36.4 min [F] and 51.6 min
      [B]; 250 mg, 35.3 min [F] and 63.6 min [B]). Recoveries (AZT and GAZT) in urine
      varied with both dosages, reflecting more a problem of accounting for the
      metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5%
      [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in
      human immunodeficiency virus-infected subjects is extremely variable, with a high
      degree of interindividual differences. Furthermore, breakfast had a marked
      influence on the absorption of AZT, suggesting that the drug should be taken in a
      fasting state.

PMID- 8257139
TI  - Analysis of pristinamycin-resistant Staphylococcus epidermidis isolates
      responsible for an outbreak in a Parisian hospital.
AB  - In 1990, over a 6-month period, an increase from 1 to 10% in the incidence of
      pristinamycin resistance among coagulase-negative staphylococci was observed in
      four intensive care units of a Parisian hospital. Twenty-three such isolates, as
      well as 25 pristinamycin-susceptible Staphylococcus epidermidis isolates, were
      collected and typed by analyzing various bacterial constituents. Two structurally
      related plasmids of 7.3 and 14.3 kb, carrying the gene vga encoding resistance to
      pristinamycin, were detected in the 23 pristinamycin-resistant coagulase-negative
      staphylococci which were identified as S. epidermidis. Although related by
      numerous common characteristics, 20 of these 23 isolates could be divided into
      two types, A (17 isolates) and B (three isolates). These types were characterized
      on the basis of their plasmid contents and hybridization patterns obtained when
      the EcoRI-digested DNA was probed with plasmid pIP1551 containing an internal
      fragment of the insertion sequence IS256. These findings suggest that the
      dissemination of type A epidemic strains was, in large part, responsible for the
      outbreak.

PMID- 8257140
TI  - 8-aminoquinolines effective against Pneumocystis carinii in vitro and in vivo.
AB  - The activities of 25 8-aminoquinolines were compared in tests assessing the
      ability of the compounds to inhibit the growth of Pneumocystis carinii in
      culture. Six compounds were effective at or below 0.03 microM: CDRI 80/53,
      NSC19894, NSC305805, NSC305812, WR182234, and primaquine. Four others were
      effective at between 0.2 and 0.03 microM: NSC305835, WR225448, WR238605, and
      WR242511. Fourteen drugs were also tested in a standard model of P. carinii
      pneumonia in rats at daily doses of 2 mg/kg of body weight in drinking water.
      CDRI 80/53, NSC305805, NSC305835, and WR225448 were extremely effective in the
      animal model. The effectiveness of WR238605, WR242511, and primaquine in the rat
      model has been reported elsewhere (M. S. Bartlett, S. F. Queener, R. R. Tidwell,
      W. K. Milhouse, J. D. Berman, W. Y. Ellis, and J. W. Smith, Antimicrob. Agents
      Chemother. 35:277-282, 1991). The length of the alkyl chain separating the
      nitrogens in the substituent at position 8 of the quinoline ring was a strong
      determinant of anti-P. carinii activity.

PMID- 8257141
TI  - Mechanistic study of inhibition of levofloxacin absorption by aluminum hydroxide.
AB  - The mechanisms of reduction in absorption of levofloxacin (LVFX) by
      coadministration of aluminum hydroxide were studied. The partition coefficient of
      LVFX (0.1 mM) between chloroform and phosphate buffer (pH 5.0) was reduced by 60
      to 70% with the addition of metal ions such as Cu2+, Al3+, and Fe2+ (0.8 mM),
      which indicated the formation of LVFX-metal ion chelates. However, there was no
      significant difference in absorption from rat intestine between the synthetic
      LVFX-Al3+ (1:1) chelate (6.75 mM) and LVFX (6.75 mM) in an in situ recirculation
      experiment. On the other hand, Al(NO3)3 (1.5 mM) significantly inhibited the
      absorption of LVFX (1.5 mM) by 20% of the control in the in situ ligated loop
      experiment, in which partial precipitation of aluminum hydroxide was observed in
      the dosing solution. Data for adsorption of LVFX and ofloxacin (OFLX) from
      aqueous solution by aluminum hydroxide were shown to fit Langmuir plots, and the
      adsorptive capacities (rmax) and the K values were 7.0 mg/g and 1.77 x 10(4) M-1
      for LVFX and 7.4 mg/g and 1.42 x 10(4) M-1 for OFLX, respectively. The rate of
      adsorption of several quinolones (50 microM) onto aluminum hydroxide (2.5 mg/ml)
      followed the order norfloxacin (NFLX) (72.0%) > enoxacin (ENX) (61.0%) > OFLX
      (47.2%) approximately LVFX (48.1%). The elution rate of adsorbed quinolones with
      water followed the rank order LVFX (17.9%) approximately OFLX (20.9%)
      approximately ENX (18.3%) > NFLX (11.9%). These results strongly suggest that
      adsorption of quinolones by aluminum hydroxide reprecipitated in the small
      intestine would play an important role in the reduced bioavailability of
      quinolones after coadministration with aluminum-containing antacids.

PMID- 8257142
TI  - Drug features that contribute to the activity of quinolones against mammalian
      topoisomerase II and cultured cells: correlation between enhancement of enzyme
      mediated DNA cleavage in vitro and cytotoxic potential.
AB  - CP-115,953 [6,8-difluoro-7-(4'-hydroxyphenyl)-1-cyclopropyl-4- quinolone-3
      carboxylic acid] is a novel quinolone that is highly active against topoisomerase
      II in vitro and in mammalian cells in culture (M. J. Robinson, B. A. Martin, T.
      D. Gootz, P. R. McGuirk, M. Moynihan, J. A. Sutcliffe, and N. Osheroff, J. Biol.
      Chem. 266:14585-14592, 1991). However, the features of the drug that contribute
      to its activity towards mammalian systems have not been characterized. Therefore,
      CP-115,953 and a series of related quinolones were examined for their activity
      against calf thymus topoisomerase II and cultured mammalian cells. CP-115,953
      stimulated DNA cleavage mediated by the type II enzyme with a potency that was
      approximately 600-fold greater than that of the antimicrobial quinolone
      ciprofloxacin and approximately 50-fold greater than that of the antineoplastic
      drug etoposide. As determined by the ability to enhance enzyme-mediated DNA
      cleavage, quinolone activity towards calf thymus topoisomerase II was enhanced by
      the presence of a cyclopropyl group at the N-1 ring position and by the presence
      of a fluorine at C-8. Furthermore, the 4'-hydroxyphenyl substituent at the C-7
      position was critical for the potency of CP-115,953 towards the mammalian type II
      enzyme. In this regard, the aromatic nature of the C-7 ring as well as the
      presence and the position of the 4'-hydroxyl group contributed greatly to drug
      activity. Finally, the cytotoxicity of quinolones in the CP-115,953 series
      towards mammalian cells paralleled the in vitro stimulation of DNA cleavage by
      topoisomerase II rather than the inhibition of enzyme-catalyzed DNA relaxation.
      This correlation strongly suggests that these quinolones promote cell death by
      converting topoisomerase II to a cellular poison.

PMID- 8257143
TI  - Pharmacokinetics and bioavailability of fluconazole in patients with AIDS.
AB  - Fluconazole pharmacokinetics were evaluated for 10 volunteers with AIDS who had
      no clinical evidence of gastroenteritis. Single 100-mg intravenous (i.v.) and
      oral (p.o.) doses were administered in a randomized, crossover design. i.v. doses
      were delivered by a constant-rate infusion over 30 min. Serum fluconazole
      concentrations were measured by gas-liquid chromatography. The i.v. and p.o.
      studies were modelled simultaneously by iterative two-stage analysis, which
      provided individual parameter estimates and a population pharmacokinetic model.
      Median areas under the concentration-time curves for i.v. and p.o. studies did
      not differ (90.6 and 99.3 micrograms/ml.h, respectively). Consistent with this
      finding, the median fractional bioavailability was 1.1 (range, 0.45 to 1.3),
      comparable to those in healthy subjects. Serum pharmacokinetics in these AIDS
      patients were generally similar to published data for healthy volunteers.
      However, following p.o. dosing, we observed a slightly delayed and highly
      variable time to maximum concentration in serum (median, 2 h; range, 15 min to 8
      h). Data were well described by a linear, two-compartment pharmacokinetic model
      with first-order absorption and elimination. Repeated-measures analysis of
      variance found no significant differences among any of the pharmacokinetic
      parameters between i.v. and p.o. studies. On the basis of our findings, we
      suggest no change in dosage of p.o. fluconazole in patients with AIDS who show no
      clinical signs of enteropathy.

PMID- 8257144
TI  - Pharmacokinetics and serum bactericidal titers of ciprofloxacin and ofloxacin
      following multiple oral doses in healthy volunteers.
AB  - Fourteen adult males participated in a randomized three-way crossover study to
      compare the pharmacokinetics and serum bactericidal titers (SBTs) of 500 mg of
      ciprofloxacin (regimen A), 750 mg of ciprofloxacin (regimen B), and 400 mg of
      ofloxacin (regimen C) administered every 12 h for seven doses. Mean steady-state
      peak concentrations in serum for regimens A, B, and C were 3.0, 4.4, and 6.5
      micrograms/ml, respectively (P < 0.01, all comparisons) and mean half-lives were
      4.5, 4.3, and 6.5 h, respectively (P < 0.05, C versus A and B). Mean steady-state
      areas under the concentration-time curve were 14.1, 21.1, and 48.1
      micrograms/h/ml for regimens A, B, and C, respectively (P < 0.05, all
      comparisons). SBTs were determined at different times postdose for three isolates
      each of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli,
      Enterobacter cloacae, and Pseudomonas aeruginosa. Mean steady-state peak SBTs for
      regimens A, B, and C, respectively, were as follows: S. pneumoniae, < 1:2, 1:8,
      1:8, S. aureus, 1:16, 1:16, 1:16; E. coli, 1: > or = 128, 1: > or = 128, 1:64; E.
      cloacae, 1: > or = 128, 1: > or = 128, 1:64; P. aeruginosa, 1:8, 1:8, 1:2. These
      differences in SBTs within each genus were statistically significant. The
      majority of predicted SBTs were within one dilution of measured SBTs. Areas under
      the serum bactericidal time curves for E. coli, E. cloacae, and P. aeruginosa
      were significantly higher for ciprofloxacin; areas under the serum bactericidal
      time curves for S. pneumoniae and S. aureus were significantly greater for
      ofloxacin. Ofloxacin achieved higher concentrations in serum than ciprofloxacin,
      but differences in in vitro activity were a more important determinant of SBTs.

PMID- 8257145
TI  - A new method to determine postantibiotic effect and effects of subinhibitory
      antibiotic concentrations.
AB  - It has been shown that bacteria in a postantibiotic (PA) phase exposed to
      subinhibitory concentrations (sub-MICs) of antibiotics show a long delay before
      regrowth. This effect has been named the PA sub-MIC effect (PA SME). In the
      present study, we have used a new method to demonstrate this phenomenon. A
      computerized incubator for bacteria, Bioscreen C (Lab Systems, Helsinki,
      Finland), which incubates the bacteria, measures growth continuously by vertical
      photometry, processes the data, and provides a printout of the results was used.
      With this method, one may easily test several antibiotics against different
      bacteria for PA effects (PAEs), PA SMEs, and SMEs. In this study, the effects of
      benzylpenicillin against beta-hemolytic streptococci and pneumococci were
      examined. The bacteria were exposed to 2, 10, or 50x MIC for 2 h, washed and
      diluted, incubated in the Bioscreen C incubator, and then exposed to 0.1 to 0.9x
      MIC. The regrowth was monitored for 20 h. The PAE was calculated as the
      difference in the time required for the exposed and unexposed bacteria to grow to
      a defined point (A50) on the absorbance curve. A50 was defined as 50% of the
      maximum absorbance for the control cultures. The PA SMEs were calculated as the
      difference in the time required for the reexposed cultures and the unexposed
      controls to reach A50. The PAEs ranged between 0.6 and 3.2 h and varied little
      with the concentration used for the induction of the PAEs. At 0.2x MIC, the PA
      SMEs were 2 to 3 h longer than the PAEs. Higher sub-MICs increased this delay
      before regrowth. Most cultures exposed to sub-MICs alone were only slightly
      affected compared with the controls.

PMID- 8257146
TI  - Effects of magnesium-aluminum hydroxide antacid on absorption of rufloxacin.
AB  - The present study was designed to determine the effects of an antacid suspension
      containing magnesium hydroxide and aluminum hydroxide (30 ml of Maalox) on the
      oral bioavailability of rufloxacin (400 mg). Rufloxacin was administered orally
      to 12 healthy volunteers according to a randomized, balanced, crossover design.
      Three treatments were administered to each subject, with a 10-day washout period
      between treatments; the treatments included rufloxacin alone, rufloxacin taken 5
      min after antacid, and rufloxacin taken 4 h before antacid. Administration of
      antacid within 5 min before the administration of rufloxacin resulted in a
      substantial decrease in rufloxacin absorption, with a mean percent relative
      bioavailability compared with control values of 64% (range, 42 to 77%).
      Administration of antacid 4 h after the administration of rufloxacin slightly
      affected the absorption of the quinolone (mean relative bioavailability, 87%;
      range, 51 to 110%). Antacids that contain magnesium and aluminum salts reduce the
      absorption of rufloxacin. The extent of this interaction depends on the time that
      elapses between administration of the two drugs.

PMID- 8257147
TI  - Reduced phototoxicity of a fluoroquinolone antibacterial agent with a methoxy
      group at the 8 position in mice irradiated with long-wavelength UV light.
AB  - A newly developed fluoroquinoline, Q-35 (8-OCH3), in which a methoxy group was
      substituted at the 8 position of the quinoline nucleus, was very stable under
      irradiation with long-wave UV light (UVA). Derivatives, a fluoroquinolone with no
      substitution (the 8-H analog) and one in which a fluorine was substituted (the 8
      F analog), were degraded in their solutions by the UVA irradiation. The
      phototoxic inducibility by these derivatives was further studied in a murine
      model. When mice were dosed orally with 800 mg of Q-35 (8-OCH3) per kg of body
      weight, the maximum dose given, and exposed to the UVA light, no inflammatory
      lesions were observed in their ears. Ear redness was marked in mice given more
      than 12.5 mg of the 8-F analog or 200 mg of the 8-H analog per kg.
      Histopathological changes, edema, and infiltration of neutrophils were also
      observed microscopically in groups receiving the 8-H or 8-F analog but not in
      groups receiving Q-35 (8-OCH3). Similar inflammatory reactions were observed to
      occur in a dose-dependent manner with other available fluoroquinolone
      antibacterial agents such as lomefloxacin, enoxacin, norfloxacin, ciprofloxacin
      and ofloxacin. These results suggest that the introduction of a methoxy group at
      the 8 position of the quinolone nucleus is important for the reduction of
      phototoxicity.

PMID- 8257148
TI  - Discrepancies in bioassay and chromatography determinations explained by
      metabolism of itraconazole to hydroxyitraconazole: studies of interpatient
      variations in concentrations.
AB  - Pharmacologic studies of itraconazole (IZ), a triazole antifungal, indicated
      unexplained differences between bioassay and chromatographic determinations and
      large variations in steady-state blood concentrations. We show that
      concentrations of a hydroxylated metabolite, hydroxyitraconazole (HIZ), are
      approximately twofold higher than IZ over a range of concentrations. Though HIZ
      and IZ appear equipotent against selected pathogens, HIZ is two to three times
      more active against a commonly used bioassay fungus but minimally affects IZ
      activity. Hence, HIZ probably contributes importantly to the therapeutic activity
      attributed to IZ and contributes approximately four to six times the activity of
      IZ in bioassays, explaining discrepancies observed between assay methods.

PMID- 8257149
TI  - Augmentation of murine tumor necrosis factor production by amphotericin B in
      vitro and in vivo.
AB  - Murine peritoneal macrophages were preincubated with amphotericin B (AMPH) and
      were then stimulated with bacterial lipopolysaccharide or streptococcal
      preparation (OK432). These macrophages produced a large amount of tumor necrosis
      factor. When administered to mice, the priming activity of amphotericin B for
      tumor necrosis factor production in vivo was also observed.

PMID- 8257151
TI  - Susceptibilities to rimantadine of influenza A/H1N1 and A/H3N2 viruses isolated
      during the epidemics of 1988 to 1989 and 1989 to 1990.
AB  - Clinical isolates of influenza A viruses identified during outbreaks in two
      winters were tested for their rimantadine susceptibilities by an enzyme-linked
      immunosorbent assay modified from that described previously by Belshe et al. (R.
      B. Belshe, B. Burk, F. Newman, R. L. Cerruti, and I. S. Sim, J. Virol. 62:1508
      1512, 1988). The infectivity titer and the 50% inhibitory concentration of
      rimantadine were calculated for each virus. Of 105 influenza virus A isolates
      tested, 28 influenza A/H1N1 isolates from the 1988 and 1989 outbreak and 77
      influenza A/H3N2 isolates from the outbreak in following year, were susceptible
      to the antiviral action of rimantadine.

PMID- 8257150
TI  - Inhibition of host cell invasion and intracellular replication of Trypanosoma
      cruzi by N,N'-bis(benzyl)-substituted polyamine analogs.
AB  - We studied the effects of two N,N'-bis(benzyl)-substituted polyamine analogs on
      the capacities of Trypanosoma cruzi to invade and multiply within a mammalian
      host cell. At concentrations as low as 1 microM, these compounds reduced
      significantly the infectivity of the parasite for rat heart myoblasts in a time
      dependent manner. Pretreatment of virulent T. cruzi trypomastigotes, but not
      myoblast pretreatment, reduced the level of infectivity. The inhibitory effects
      started to subside 3 h after removal of the drugs and were no longer detectable
      after 4 h. A significant decrease in the rate of intracellular amastigote
      multiplication was also seen when the drugs were added to myoblast cultures which
      had been previously infected with untreated T. cruzi. These results show that
      N,N'-bis(benzyl)-substituted polyamine analogs meet the two most important
      criteria for potential chemotherapeutic agents against T. cruzi infection,
      namely, inhibition of both host cell invasion and intracellular replication by
      this parasite.

PMID- 8257152
TI  - In vitro activity of penciclovir against clinical isolates of acyclovir-resistant
      and foscarnet-resistant herpes simplex virus.
AB  - We tested 23 clinical isolates of acyclovir-susceptible, acyclovir-resistant, and
      foscarnet-resistant herpes simplex virus for susceptibility to penciclovir.
      Isolates showed cross-resistance to penciclovir and acyclovir, but penciclovir
      retained a relative activity against foscarnet-resistant isolates. Its clinical
      utility for the treatment of resistant herpes simplex virus infections remains to
      be studied.

PMID- 8257153
TI  - Antibacterial activities of OPC-17116, ofloxacin, and ciprofloxacin against 200
      isolates of Neisseria gonorrhoeae.
AB  - OPC-17116 is a new fluoroquinolone with potent activity against aerobic and
      anaerobic organisms. We evaluated the susceptibilities of 200 clinical gonococcal
      isolates including organisms with plasmid and chromosomally mediated resistance
      to beta-lactams and tetracycline. The antibiotics studied included OPC-17116,
      ofloxacin, ciprofloxacin, penicillin, tetracycline, erythromycin, azithromycin,
      and ceftriaxone. All isolates tested were susceptible to the quinolone class of
      antibiotics. The MICs of ciprofloxacin, ofloxacin, and OPC-17116 for 90% of
      isolates tested were 0.004, 0.03, and 0.004 micrograms/ml, respectively. For
      organisms with chromosomally mediated resistance to penicillin and tetracycline,
      geometric mean MICs of all antibiotics including the quinolones were increased.

PMID- 8257154
TI  - Metabolism and in vitro antiretroviral activities of bis(pivaloyloxymethyl)
      prodrugs of acyclic nucleoside phosphonates.
AB  - Bis(pivaloyloxymethyl) [bis(pom)] derivatives of various acyclic nucleoside
      phosphonates--9-(2-phosphonylmethoxyethyl)adenine (PMEA), 9-(2
      phosphonylmethoxypropyl)adenine (PMPA), and 9-(2
      phosphonylmethoxypropyl)diaminopurine (PMPDAP)--were found to exhibit 9- to 23
      fold greater antiviral activity than their corresponding unmodified compounds.
      The cytotoxicity of the bis(pom) analogs was also increased by various degrees,
      thus altering the therapeutic indexes of these compounds. Metabolic studies using
      [3H]bis(pom)PMEA and [3H]PMEA as model compounds suggested a > 100-fold increase
      in the cellular uptake of the bis(pom) derivative and formation of active
      diphosphorylated metabolite. However, the bis(pom) derivatives were chemically
      unstable and highly susceptible to serum-mediated hydrolysis, factors which limit
      their potential utility for intracellular drug delivery.

PMID- 8257156
TI  - Shared governance, super units in the surgical suite. Management ideas for
      empowerment, innovation.

PMID- 8257157
TI  - Recommended practices. Laser safety in the practice setting. Association of
      Operating Room Nurses.

PMID- 8257155
TI  - Susceptibilities of oxyR regulon mutants of Escherichia coli and Salmonella
      typhimurium to isoniazid.
AB  - Escherichia coli and Salmonella typhimurium are normally resistant to > 500
      micrograms of the antituberculosis drug isonicotinic acid hydrazide (isoniazid;
      INH) per ml. Susceptibility to INH (< 50 micrograms/ml) has now been found for
      mutants that are deficient in OxyR, the oxidative stress response regulator. Two
      OxyR-regulated enzymes, alkyl hydroperoxide reductase and hydroperoxidase I, were
      identified as playing important roles in INH resistance. OxyR regulon mutants
      should be useful for identifying other determinants of INH resistance in both E.
      coli and Mycobacterium tuberculosis and for finding new INH-like drugs.

PMID- 8257158
TI  - States continue to wrestle with HIV/AIDS issues.

PMID- 8257159
TI  - Be courageous--take care of yourself.

PMID- 8257160
TI  - Organ transplantation.

PMID- 8257161
TI  - Organ transplantation.

PMID- 8257162
TI  - Tonsillectomy, adenoidectomy in the day surgery unit: a case study.

PMID- 8257163
TI  - Transurethral prostate resection not state-of-the-art.

PMID- 8257164
TI  - What future will perioperative nurses choose by 2010?
AB  - The future does not just happen. Events of yesterday provide the brick and mortar
      for today. The future of perioperative nursing practice depends on how we arrange
      the brick and mortar today. We cannot predict the future; the future is chosen
      based on what actions we plan for tomorrow. Health care, surgical care, and
      illness care will change a great deal as we enter the twenty-first century. Our
      specialty cannot afford to be preoccupied with past accomplishments, reacting
      only to daily events rather than creating a chosen future. AORN has taken a major
      step by establishing the Project 2000 teams to analyze the present and plan for
      the future. Members must be willing to abandon the status quo. Looking beyond
      current practice to the expanding edges of perioperative nursing offers new
      opportunities. Where will we be in 2010? The future is ours to choose.

PMID- 8257165
TI  - New technology goes to Taiwan. Perioperative nurses make international journey
      with new technology.

PMID- 8257166
TI  - Arthroscopic temporomandibular joint surgery. A new approach to temporomandibular
      joint disorders.
AB  - Temporomandibular joint arthroscopy provides a minimally invasive surgical means
      of gaining access to the TMJ. It offers valuable diagnostic information and
      options in the treatment of TMJ dysfunction. Recovery and healing are more rapid,
      thereby reducing patient discomfort and rehabilitation time. It is estimated that
      there is an 85% to 90% success rate of this procedure. Patients with TMJ problems
      resulting from an emotional component can be helped, but their pain may persist
      because of related muscle tension.

PMID- 8257167
TI  - Endoscopic lithotripsy for urinary calculi. Treatment alternatives.

PMID- 8257168
TI  - Laser lithotripsy. Patient care, staff education.
AB  - The high cost of laser equipment and the required specialization of staff members
      make extension of laser lithotripsy to every hospital impractical. At present, in
      Ontario, laser lithotripsy is available only in Toronto and Kingston, and ESWL is
      available only in Toronto and London. Laser lithotripsy is a viable alternative
      to invasive surgical treatment of urinary calculi that are resistant to ESWL. For
      the suitable candidate, laser lithotripsy is a welcome alternative to an
      extensive surgical procedure and recovery period. Hospitalization is reduced
      significantly, and patients can return to work after the calculus and residue
      have been passed. Patients can be managed safely and effectively, resulting in
      reduced morbidity and mortality and reduced cost in time and expense to the
      patient and hospital.

PMID- 8257169
TI  - In-house sterilization of implants. Standardizing the procedure.

PMID- 8257170
TI  - AORN membership survey results.
AB  - The 1993 survey is the first step in a planned, systematic method of eliciting
      members' opinions, demographic information, and program preferences. The data
      collected will be used to analyze current programs and services and plan for the
      future. There are limitations to survey research. Questions may be deleted
      accidentally or worded in such a way that respondents answer them incorrectly. In
      this survey, there were limitations in the questions pertaining to salary.
      Respondents were not asked to identify if they were employed full time or part
      time when they selected salary ranges. Even with these limitations, the
      respondent population appears to be of sufficient size to ensure a validity in
      the 95% range.

PMID- 8257171
TI  - Nutritional support in liver disease.

PMID- 8257172
TI  - Cytokines in childhood rheumatic diseases.

PMID- 8257173
TI  - Remission death in acute lymphoblastic leukaemia: a changing pattern.
AB  - The pattern of remission deaths was examined in 842 children with acute
      lymphoblastic leukaemia (ALL) treated at a single centre over 18 years. The
      mortality rate from leukaemia fell significantly during three consecutive time
      periods during which treatment became progressively more intensive and that
      during remission induction fell from 3.5% to under 1%, but the rate of death in
      remission stayed constant at 5-6%. The factors associated with an increased risk
      of remission death were: young age, a higher leucocyte count, bone marrow
      transplantation, and Down's syndrome. The pattern of remission deaths changed
      over the years; measles and herpes viruses decreased while deaths associated with
      periods of intensification and gut toxicity increased. Four children developed
      second neoplasms. Treatment of ALL is still associated with a significant risk of
      death in remission but the pattern of infective deaths has changed. Many should
      be avoidable by provision of adequate supportive care, close supervision after
      periods of intensive treatment, and appropriate antibiotic, antifungal, and
      cytokine therapy.

PMID- 8257174
TI  - Increased plasma thyroid stimulating hormone in treated congenital
      hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone
      status, and daily dose of thyroxine.
AB  - Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first
      four years of treatment in 418 children with congenital hypothyroidism,
      identified by neonatal screening, were examined in relation to paired
      measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836),
      triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated
      daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was
      above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to
      severity of hypothyroidism at diagnosis. Mean values for thyroxine and free
      thyroxine, and to a lesser extent free triiodothyronine, were consistently lower
      in samples with TSH concentrations over 7 mU/l and this was the case in patients
      with either severe or less severe hypothyroidism. Raised TSH concentrations were
      also associated with lower mean doses of thyroxine (micrograms/kg/day) but here
      the mean doses of thyroxine in children with severe hypothyroidism were higher
      than in the children with less severe hypothyroidism. The mean dose of thyroxine
      associated with low/normal TSH values was highest in the first 6 months and fell
      progressively. Thyroxine dose was significantly related to thyroxine and free
      thyroxine concentrations but not to triiodothyronine and free triiodothyronine
      and the latter appeared to be of limited value as measures of plasma thyroid
      hormone status during treatment.

PMID- 8257175
TI  - Use of hospital inpatient care in adolescence.
AB  - Epidemiological information about detailed patterns of physical morbidity within
      the adolescent age group is not generally available. To illustrate the
      distinctive patterns of morbidity indicated by the use of hospital inpatient
      care, hospital admission rates in the Oxford region (1979-86) were analysed at
      each single year of age from 10 to 19 years. At the age of 10 years 22% of
      general hospital admissions were to paediatrics, 24% to general surgery, 23% to
      ear, nose, and throat surgery, and 20% to trauma and orthopaedics. By 14 years of
      age only 6% of general hospital admissions were to paediatrics. By 16 years of
      age 24% of general hospital admissions of young women were to gynaecology and 40%
      of admissions of young men were to trauma and orthopaedics. The most common
      reason for hospital admission in young men was head injury and the second most
      common was appendicectomy. Termination of pregnancy was the single most common
      reason for admission for girls aged 15 and 16 years; childbirth and terminations
      were the most common reasons for admission in girls aged 17-19 years and over.
      Self poisoning was also common in older teenage girls. Younger girls were
      admitted most commonly for tonsillectomy. Most admissions of adolescents are thus
      for surgical rather than medical reasons and some of the most common individual
      reasons for admission are attributable to behavioural factors rather than disease
      processes.

PMID- 8257176
TI  - Effects of a few food diet in attention deficit disorder.
AB  - Seventy-eight children, referred to a diet clinic because of hyperactive
      behaviour, were placed on a 'few foods' elimination diet. Fifty nine improved in
      behaviour during this open trial. For 19 of these children it was possible to
      disguise foods or additives, or both, that reliably provoked behavioural problems
      by mixing them with other tolerated foods and to test their effect in a placebo
      controlled double blind challenge protocol. The results of a crossover trial on
      these 19 children showed a significant effect for the provoking foods to worsen
      ratings of behaviour and to impair psychological test performance. This study
      shows that observations of change in behaviour associated with diet made by
      parents and other people with a role in the child's care can be reproduced using
      double blind methodology and objective assessments. Clinicians should give weight
      to the accounts of parents and consider this treatment in selected children with
      a suggestive medical history.

PMID- 8257177
TI  - Reference ranges for respiratory rate measured by thermistry (12-84 months).
AB  - Previous studies of respiratory rate in children have had a number of
      methodological problems. The aim of this study was to construct age specific
      reference ranges for respiratory rate. Respiratory rate in children attending
      childcare centres, kindergartens, and schools was measured using a nasal
      thermocouple to obtain respiratory waveforms. Reference ranges were constructed
      using data from 293 awake children between 12 and 84 months, and from 123
      sleeping children between 12 and 60 months. The mean respiratory rate declined
      with increasing age and was significantly lower, with lower variability, during
      sleep than wakefulness. Neither the awake nor sleeping reference ranges were
      significantly affected by sex, nor by the presence of past respiratory nor
      current respiratory symptoms.

PMID- 8257178
TI  - Mycoplasma pneumoniae infection and neurological disease.
AB  - The cases are reported of 13 children seen over a 22 month period who presented
      with a variety of acute neurological illnesses associated with Mycoplasma
      pneumoniae infection. Although presentation with a decreased level of
      consciousness or seizures was common, psychosis, hemiparesis, cranial nerve
      palsies, and Guillain-Barre syndrome were also seen. In contrast with published
      reports, only one child had an associated chest infection. Although some children
      have been left with residual disability, most have made a complete recovery. In
      this recent experience, M pneumoniae is a not rare cause of neurological illness
      in childhood and may present in unusual ways.

PMID- 8257179
TI  - Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity
      during treatment for acute lymphoblastic leukaemia.
AB  - Two children with acute lymphoblastic leukaemia (ALL) taking daily 6
      mercaptopurine as part of a national UK therapeutic trial repeatedly developed
      profound myelosuppression on 25% of the standard protocol dose. Both were found
      to have undetectable intracellular activity of thiopurine methyltransferase
      (TPMT), an enzyme controlling one of the major alternative catabolic pathways of
      6-mercaptopurine, and both produced higher concentrations of cytotoxic drug
      metabolites at 10-25% of the protocol dose than other patients taking 100%. It is
      supposed that these patients represent the 0.33% of the normal population
      constitutionally lacking TPMT. It is important to recognise such individuals both
      to avoid fatal bone marrow failure through inadvertent overdosage, and to be
      reassured that an adequate drug effect can be achieved at around 10% of the
      standard dose.

PMID- 8257180
TI  - Non-cardiac benefits of human recombinant erythropoietin in end stage renal
      failure and anaemia.
AB  - Recombinant human erythropoietin (r-HuEpo) is now available to correct the
      anaemia of end stage renal failure. The clinical consequences of increasing the
      haemoglobin concentration in children on dialysis are incompletely documented; a
      placebo controlled study is essential when assessing subjective changes, for
      example in appetite or other aspects of quality of life. A single blind, placebo
      controlled crossover study in 11 children with end stage renal failure was
      performed to assess the clinical benefits resulting from correction of anaemia.
      Ten of the 11 children completed 36 weeks of the study and seven completed both
      24 week limbs. Subcutaneous administration of r-HuEpo twice a week resulted in an
      increase in haemoglobin concentration, from 73 to 112 g/l. This was associated
      with an objective improvement in exercise tolerance, and a subjective improvement
      in physical performance and health, and better school attendance. No consistent
      effect was seen on appetite, growth, psychosocial functioning, biochemical
      control, or peritoneal dialysis efficiency. A small but clinically unimportant
      increase in systolic and diastolic blood pressure was seen in five children. One
      child on antihypertensive treatment required an increase in dosage during r-HuEpo
      while another child required a reduction in treatment. These findings, together
      with the important cardiac benefits previously described during r-HuEpo
      treatment, support the use of r-HuEpo in all children with end stage renal
      failure and anaemia.

PMID- 8257181
TI  - Thoracic empyema: a study of 56 patients.
AB  - Fifty seven children with thoracic empyema (37 boys and 20 girls) aged less than
      12 years were seen at the University of Port Harcourt Teaching Hospital between
      January 1989 and December 1991. Staphylococcus aureus was the most common
      organism isolated from the pus of these patients (36 (63%) patients). Pseudomonas
      aeruginosa, the next most common organism, was isolated in 10 (18%) patients. The
      most common symptoms at presentation were acute illness with fever and cough (51
      (89%) patients). All the patients were treated with closed intercostal tube
      drainage and appropriate antibiotics. Decortication was resorted to in only one
      patient. There were two deaths and the overall survival rate was 97%.

PMID- 8257182
TI  - Effect of diet on infant subcutaneous tissue triglyceride fatty acids.
AB  - Having demonstrated a deficiency in infant cerebral cortex docosahexaenoic acid
      of formula fed compared with breast milk fed infants, we sought to identify why
      the extensive subcutaneous tissue triglyceride fatty acid reserves in term new
      born infants appeared to be ineffectual in its prevention. In addition to 24 term
      and six preterm infants who died from 'cot death', tissue was analysed from four
      perinatal surgical patients and in the former the results were correlated with
      dietary milk intake. The higher amounts (about 15% by weight) of unsaturated
      linoleic acid supplied in the formula milks were quantitatively incorporated into
      the subcutaneous tissue largely at the expense of the saturated palmitic acid
      possibly compromising adipocyte fluidity. The six preterm infants were in two
      formula fed groups and there was only one significant difference, namely a higher
      subcutaneous tissue concentration of alpha-linolenic acid in one of the preterm
      groups, distinguishing them from their term counterparts. This may imply that the
      enzymes involved in absorption and digestion of fatty acids are mature in the
      preterm infant. From birth the mean weight percentage of docosahexaenoic acid
      (0.4%) fell rapidly to undetectable levels (< 0.05%) in the formula fed group
      after about two months. It is therefore concluded that if breast feeding is not
      possible then a minimum daily requirement of 30 mg docosahexaenoic acid
      (approximately 0.2 g/100 g fatty acids) should be supplied in formulas designed
      for term infants to prevent the cerebral cortical deficiency of docosahexaenoic
      acid.

PMID- 8257183
TI  - Decline in hepatitis B infection in sickle cell anaemia and beta thalassaemia
      major.
AB  - Seventy five Saudi children, 55 with sickle cell anaemia and 20 with beta
      thalassaemia major, who were negative for all hepatitis B virus (HBV) markers
      five years ago were recently investigated for exposure to HBV and hepatitis C
      virus (HCV) infection. Of the 55 patients with sickle cell anaemia and 20 with
      beta thalassaemia major, 20 and five patients respectively had been vaccinated
      against HBV earlier and all of them still had protective antibody (anti-HBs 42-96
      IU) 3-5 years after vaccination and there was no vaccine failure. Among the non
      vaccinated children the exposure rates to HBV were 14.3% among those with sickle
      cell anaemia and 26.7% among those with beta thalassaemia and this was not
      statistically significant when compared with the exposure rate to HBV among the
      general paediatric population (20.1%). Anti-HCV positivity among those with beta
      thalassaemia major and sickle cell anaemia was 70% and 18.2%, respectively, and
      this was significantly higher than anti-HCV positivity among the control group
      (0.8%). Anti-HCV positivity was directly related to the amount of blood
      transfused and to the duration of transfusion. The results of the study show that
      although the exposure rates to HBV among patients with sickle cell anaemia and
      beta thalassaemia major were not significantly different than that among the
      general paediatric population, infection with HBV still takes place among non
      vaccinated patients despite strict precautionary measures taken. Hence early
      vaccination against HBV would probably be the only effective way of controlling
      HBV infection. For HCV infection, and because a vaccine against HCV is still not
      available, preventive measures such as blood screening for anti-HCV before
      transfusion and stringent infection control measures are crucial steps to be
      implemented for the control of spread of HCV among these groups of patients.

PMID- 8257184
TI  - Persistent mild hip deformation in preterm infants.
AB  - Preterm infants often develop a postural deformation of the legs with wide hip
      abduction and external rotation giving a 'frog leg' posture. It has been shown
      that the deformation persists at the age of 3-4.5 years and the use of postural
      techniques aimed at reducing the deformation is recommended.

PMID- 8257185
TI  - Overtight nappy precipitating thrombosis in antithrombin III deficiency.
AB  - An antithrombin III deficient infant presented with iliac vein thrombosis,
      apparently precipitated by an overtight nappy. Venous thrombosis is unusual, both
      in normal and in antithrombin III deficient children, but children with venous
      thrombosis should have their natural anticoagulants assayed and obvious risk
      factors avoided.

PMID- 8257186
TI  - Monitoring the vaccine cold chain.
AB  - Maintaining the vaccine cold chain is an essential part of a successful
      immunisation programme. A continuous electronic temperature monitor helped to
      identify breaks in the cold chain in the community and the study led to the issue
      of proper guidelines and replacement of faulty equipment.

PMID- 8257187
TI  - Isolated vitamin E deficiency and progressive ataxia.
AB  - A case of progressive spinocerebellar syndrome due to isolated vitamin E
      deficiency is reported. Measurement of the vitamin E concentration in serum
      should be included when investigating all children with unexplained, progressive
      ataxia, even in the absence of malabsorption. Replacement treatment in patients
      with a vitamin E deficiency can arrest or improve the associated neurological
      disorder.

PMID- 8257188
TI  - Identification and management of problem eaters.

PMID- 8257190
TI  - Munchausen syndrome.

PMID- 8257189
TI  - Infantile spasms.

PMID- 8257191
TI  - Surgery and benign facial lesions.

PMID- 8257192
TI  - The power of words.

PMID- 8257193
TI  - Designing interventions in psychosocial research.
AB  - There is little guidance in the literature on how to design cost-effective
      interventions for preventing or treating psychosocial health care problems. Four
      sources of information are described for developing interventions that are based
      on a strong theoretical and empirical foundation: (1) an explicit theory for
      intervention, (2) supporting descriptive data, (3) an evaluation of possible
      intervention strategies that are consistent with the theory and the supporting
      data, and (4) focus groups to examine the feasibility and external validity of
      the intervention before formal testing.

PMID- 8257194
TI  - An exploration of the characteristics of post-traumatic stress disorder in
      reserve forces deployed during Desert Storm.
AB  - Post-traumatic stress disorder (PTSD), previously defined in Vietnam War
      veterans, was described in 251 Desert Storm reservists. The Mississippi Scale,
      Revised, was used with a brief demographic profile to survey Army, Marine, and
      Air Force personnel who had been deployed to Saudi Arabia. Age, sex, marital
      status, race, rank, duty, length of deployment, and branch of service were not
      found to be significantly related to PTSD symptoms. However, those surveyed
      within 3 to 6 months of homecoming reported significantly greater symptoms than
      those surveyed after 6 months. Five percent of subjects were found to have
      clinically diagnostic levels of PTSD symptoms 6 months after homecoming.
      Individuals who expressed difficulty discussing their experiences with more than
      one person also showed significantly higher PTSD scores. These findings indicate
      that readjustment reactions were prevalent during the first 6 months and that
      PTSD could be identified in 5% of the Desert Storm veterans.

PMID- 8257195
TI  - Explaining social isolation through concept analysis.
AB  - Psychiatric nurses need to develop protocols and interventions for clients who
      are at risk for social isolation or who are socially isolated. Development of
      protocols and interventions should not be performed unless nurses have a clear
      understanding of what the term social isolation means. Existing definitions of
      social isolation have been vague and contradictory. This article presents a
      concept analysis of social isolation.

PMID- 8257196
TI  - Comparison of effectiveness of group interventions for depression in women.
AB  - The purpose of this study was to evaluate the effectiveness of a structured
      cognitive-behavioral group intervention designed by Verona Gordon to reduce
      depression in women. An experimental three group pretest and posttest design was
      used. Women were randomly assigned to the structured and support groups. The
      structured group was found to be significantly more effective in reducing
      depression, hopelessness, anxiety, and improving self-esteem than either the
      support or untreated control groups.

PMID- 8257197
TI  - Effects of individualized music on confused and agitated elderly patients.
AB  - The Progressively Lowered Stress Threshold Model in conjunction with an
      identified theoretical basis provides a framework for the use of individualized
      music in individuals with Dementia of the Alzheimer's Type (DAT). The effects of
      individualized music is explored in five elderly patients who are confused and
      agitated and residing in a long-term care facility. The Modified Cohen-Mansfield
      Agitation Inventory is used to measure the outcome. The immediate and 1-hour
      residual effects suggest the potential of individualized music as an alternative
      approach to the management of agitation in confused elderly patients.

PMID- 8257198
TI  - Catastrophic reactions and other behaviors of Alzheimer's residents: special unit
      compared with traditional units.
AB  - Using a quasi-experimental pretest/posttest design, the effects of a Special Care
      Unit (SCU) on the incidence of catastrophic reactions and other behaviors of
      nursing home residents with Alzheimer's disease (AD) were examined. Findings
      indicate significantly fewer catastrophic reactions and other selected behavior
      changes occurred during the posttest period for subjects in the experimental
      group compared with the subjects in the control group. Implications for
      psychiatric consultation/liaison nurses (PCLNs) working with this vulnerable
      population are discussed.

PMID- 8257199
TI  - The parallel process of resistance by clients and therapists to starting groups:
      a guide for nurses.
AB  - Group psychotherapy is well recognized as a treatment modality with a powerful
      healing capacity. Yet, as experienced group therapists will attest, it is
      immensely difficult to begin a group. Assembling clients who have sufficiently
      dealt with their resistance to join a psychotherapy group is a painstaking
      process. Students in group psychotherapy training programs also find beginning a
      new group an arduous and frustrating task. The authors have had the benefit of
      postgraduate group psychotherapy training program to build on the expertise and
      skills already familiar to the Clinical Nurse Specialist. Our understanding of
      the parallel process in the resistance to beginning a group grew out of our
      training experience. We will explore within the parallel process framework some
      of the factors that make the development of a group psychotherapy practice as
      complex. Parallels will be drawn between clinician resistance to beginning a new
      group and client resistance to joining a group.

PMID- 8257200
TI  - A special population: nursing diagnoses for the psychiatric client with mental
      retardation.
AB  - Adult psychiatric clients who are also mentally retarded represent a population
      with unique nursing care needs. Nursing diagnoses provide information about
      current functional and potential problems, thus aiding in diagnosis and
      treatment. Additional research is needed regarding nursing diagnoses for this
      population.

PMID- 8257201
TI  - Letter from China (No. 4).

PMID- 8257202
TI  - Extreme abuse of confidentiality.

PMID- 8257203
TI  - Evaluating new physical treatments.

PMID- 8257204
TI  - Rhazes.

PMID- 8257206
TI  - Epidemiological study of the relation between arthritis of the hip and hip
      fractures.
AB  - OBJECTIVES: To clarify the nature of the relation between hip fractures and
      osteoarthritis. METHODS: The study was a population based case-control study
      conducted in Sydney, Australia. Four hundred and sixteen men and women aged 65
      years and over were recruited (209 cases, 207 controls). The presence of
      osteoarthritis was based on self reported pain, swelling, or stiffness of joints
      in the past year. RESULTS: Among 189 subjects aged 65 to 79 years, but not in
      older subjects, there was an inverse relation between self reported arthritis in
      any joint(s) and risk of hip fracture: the age and gender adjusted odds ratio was
      0.52 (95% confidence interval 0.27 to 0.98). The prevalence of self reported
      arthritis of the hip was much lower in patients with hip fracture (4%) than in
      controls randomly selected from the community (13%); the age and gender adjusted
      odds ratio was 0.33 (95% confidence interval 0.15 to 0.74). There was also an
      inverse association between the number of joints reported to be affected by
      arthritis and risk of hip fracture. These associations were not explained by
      differences between cases and controls in body mass index or physical activity.
      CONCLUSIONS: The findings of this study support the hypothesis that there is a
      causal association between osteoarthritis and osteoporosis of the hip.

PMID- 8257205
TI  - A double blind randomised trial of low power laser treatment in rheumatoid
      arthritis.
AB  - OBJECTIVES: To define the value of low power laser treatment in small joint
      rheumatoid arthritis. METHODS: Twenty five women with active disease were
      recruited. The metacarpophalangeal and proximal interphalangeal joints of one
      hand were treated with 12 J/cm2 for 30 s with a gallium-aluminium-arsenate laser.
      The other hand received a sham laser treatment designed so that neither therapist
      nor patient could distinguish the active laser from the sham laser. Each patient
      received 12 treatments over four weeks. The following parameters were measured:
      pain as assessed by visual analogue scale; range of joint movements; grip
      strength; duration of early morning stiffness, joint circumference, Jebsen's hand
      assessment; drug usage; total swollen joint counts; Arthritis Impact Measurement
      Scales; three phase bone scans; haematological and serological tests. RESULTS: A
      total of 72% of patients reported pain relief but this reduction was reported
      equally in both hands. No significant changes were seen in other clinical,
      functional, scintigraphic, or laboratory features. Neither patients nor staff
      were able to detect which hand was treated with the active laser. CONCLUSION:
      When this specific laser and dose regimen was used, low power laser treatment had
      no objective effect on patients with rheumatoid arthritis. It did appear to
      produce analgesia through a powerful placebo effect.

PMID- 8257207
TI  - Gadolinium-DTPA enhanced magnetic resonance imaging of bone cysts in patients
      with rheumatoid arthritis.
AB  - OBJECTIVES: To examine the contents of intraosseous cysts in patients with
      rheumatoid arthritis (RA) through the signal intensity characteristics on
      gadolinium-DTPA (Gd-DTPA) enhanced magnetic resonance imaging. METHODS: The hand
      or foot joints of nine patients with the cystic form of RA (where the initial
      radiological abnormality consisted of intraosseous cysts without erosions) were
      imaged before and after intravenous administration of Gd-DTPA. A 0.6 unit, T1
      weighted spin echo and T2* weighted gradient echo were used to obtain images in
      at least two perpendicular planes. RESULTS: Most cysts showed a low signal
      intensity on the non-enhanced T1 weighted (spin echo) images and a high signal
      intensity on the T2* weighted (gradient echo) images, consistent with a fluid
      content. No cyst showed an enhancement of signal intensity on the T1 weighted
      images after intravenous administration of Gd-DTPA, whereas synovium hyperplasia
      at the site of bony erosions did show an increased signal intensity after Gd
      DTPA. Magnetic resonance imaging detected more cysts (as small as 2 mm) than
      plain films, and the cysts were located truly intraosseously. In six patients no
      other joint abnormalities were identified by magnetic resonance imaging; the
      three other patients also showed, after Gd-DTPA administration, an enhanced
      synovium at the site of bony erosions. CONCLUSIONS: It is suggested that
      intraosseous bone cysts in patients with RA do not contain hyperaemic synovial
      proliferation. The bone cysts in patients with the cystic form of RA may be the
      only joint abnormality.

PMID- 8257208
TI  - Environmental factors predicting nephritis in systemic lupus erythematosus.
AB  - OBJECTIVES: To evaluate social class, ethnic origin, and various endocrine
      variables as potential risk factors in the development of nephritis in patients
      with systemic lupus erythematosus (SLE). METHODS: A cross-sectional survey was
      carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's
      Hospital from March to October 1992 using retrospective survival data. The main
      outcome measure was the duration of SLE before the onset of nephritis. RESULTS:
      Two hundred and ninety six women and 11 men were studied; the male patients were
      excluded from the analysis. Univariate analysis showed an increased risk of
      nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis
      at five years, in patients of lower social class, in patients who did not drink
      alcohol, and in those with a history of fetal loss after the onset of lupus. No
      significant effect of the age of onset of SLE, use of oral contraceptives, normal
      pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin
      did not influence the risk of nephritis independently of social class.
      CONCLUSIONS: Factors associated with socioeconomic deprivation may increase
      disease severity in patients with SLE.

PMID- 8257209
TI  - Circulating T cell subtypes in polymyalgia rheumatica and giant cell arteritis:
      variation in the percentage of CD8+ cells with prednisolone treatment.
AB  - OBJECTIVES: Some reports have described a decreased percentage of circulating
      CD8+ cells in patients with polymyalgia rheumatica and giant cell arteritis
      (PMR/GCA) before treatment and persisting for some months during treatment with
      corticosteroids. Other studies have found no such changes. There are overt
      methodological variations between these studies and there may also hidden
      differences, such as the timing of blood samples. The purpose of this study was
      to investigate T cell subtypes in patients with PMR/GCA while controlling for
      variables known to affect T cells. METHODS: Circulating T cell subsets were
      measured in 36 patients with PMR/GCA before and during treatment with
      prednisolone. Blood samples during treatment were taken before the daily dose of
      prednisolone. The whole blood lysis method was used followed by flow cytometry.
      RESULTS: Compared with controls, CD8+ cells were not reduced before treatment in
      patients with PMR/GCA (0.44 x 10(9)/l; 28% of lymphocytes). CD4+ cells were also
      normal (0.78 x 10(9)/l; 48% of lymphocytes). During treatment with prednisolone
      total T cells increased from 1.18 to 1.59 x 10(9)/l and CD4+ cells increased from
      0.78 to 1.05 x 10(9)/l. The percentage of CD8+ cells decreased on treatment from
      28 to 25%. CONCLUSIONS: This study does not confirm the finding of some groups
      that the percentage of circulating CD8+ cells is reduced in patients with PMR/GCA
      before treatment. It does show that the percentage of CD8+ cells decreases during
      treatment with corticosteroids. This needs to be considered when designing
      studies of lymphocyte subsets in diseases treated with corticosteroids.

PMID- 8257210
TI  - Maintenance of the synthesis of large proteoglycans in anatomically intact murine
      articular cartilage by steroids and insulin-like growth factor I.
AB  - OBJECTIVES: The exact regulation of the synthesis of cartilage specific
      molecules, such as collagen type II and aggrecan, by articular chondrocytes is
      unknown, but growth factors and hormones probably play an important part. The
      effects of glucocorticosteroids (prednisolone and triamcinolone), in combination
      with insulin-like growth factor I (IGF-I), on the synthesis and hydrodynamic
      volume of proteoglycans from murine patellar cartilage were investigated.
      METHODS: The in vitro effect of IGF-I and steroids on proteoglycan synthesis in
      murine patellar cartilage was evaluated by [35S]sulphate incorporation in
      combination with dissociative gel chromatography using a Sephacryl S-1000 column.
      The impact of in vivo prednisolone (0-5 mg/kg) on proteoglycan synthesis in
      murine patellar cartilage was analysed by [35S]sulphate incorporation immediately
      after dissection from the knee joint. RESULTS: Prednisolone stimulated
      proteoglycan synthesis in murine patellar cartilage from normal knees and in
      cartilage from knees injected with papain in vitro in the absence and presence of
      IGF-I. Moreover, oral administration of prednisolone for seven days to C57Bl10
      mice resulted in enhanced proteoglycan synthesis in patellar cartilage. The
      incubation of patellar cartilage for 48 hours without serum or growth factors led
      to the synthesis of proteoglycans with a smaller hydrodynamic volume than those
      synthesised immediately after dissection of the patellae. This could either be
      circumvented by the addition of IGF-I or by the addition of glucocorticosteroids
      (prednisolone or triamcinolone) to the culture medium. CONCLUSIONS: These results
      show that in a dose range of 0.0003-0.3 mmol/l, glucocorticosteroids, like IGF-I,
      stimulate proteoglycan synthesis and maintain the synthesis of hydrodynamically
      large proteoglycans by chondrocytes from murine articular cartilage. This
      indicates that glucocorticosteroids might play a part in the preservation of
      matrix integrity in articular cartilage.

PMID- 8257211
TI  - Pathogenic serum IgG anticardiolipin antibodies and the idiotypic network.
AB  - OBJECTIVES: To determine whether active immunisation of mice with pathogenic
      anticardiolipin antibodies (IgG and IgM), derived from the serum of a patient
      with the antiphospholipid syndrome, could dysregulate the idiotypic cascade and
      induce the production of anti-anti-anti-cardiolipin (Ab3) with anticardiolipin
      activity by the mice with the association of overt antiphospholipid syndrome.
      METHODS: Anticardiolipin antibodies were purified from the serum of a patient
      with the antiphospholipid syndrome. The purified anticardiolipin antibodies were
      used to immunise mice at the footpads and the mice were then followed up for
      serological and clinical manifestations of the antiphospholipid syndrome.
      RESULTS: The IgG anticardiolipin antibody was found to be monospecific and to
      bind cardiolipin with high affinity. Immunisation of naive BALB/c mice with the
      purified IgG anticardiolipin antibody was followed by production in the mice of
      sustained high titres of IgG anticardiolipin antibody, associated with a
      prolonged activated partial thromboplastin time (64.5 (9.7) v 30.1 (1.7) seconds
      in control mice) and thrombocytopenia (0.4 (0.06) x 10(9) v 1.0 (0.09) x 10(9)/l
      platelets in controls). The titres of other autoantibodies (for example,
      antibodies to DNA, histone), though high after the immunisation, decreased
      rapidly and were almost undetected one month after the boost injection. The mice
      immunised with the IgG anticardiolipin antibody showed low fecundity (36% of mice
      became pregnant v 62% in the group immunised with control IgG). The pregnant mice
      had an increased resorption rate (the equivalent of fetal loss in the human) of
      61 (9)% v 5 (4)% in the control group. The mean (SD) embryo and placental weights
      in mice with the antiphospholipid syndrome were significantly lower than in the
      mice injected with control IgG (641 (210) and 103 (14) mg v 1303 (105) and 145
      (8) mg respectively. The IgM anticardiolipin antibodies purified from the same
      patient were found to be polyspecific, binding with low affinity to
      anticardiolipin antibodies and double stranded DNA, and carried the anti-DNA
      idiotype 16/6. Mice immunised with the purified IgM anticardiolipin antibodies,
      though showing reduced fecundity (30%), had only a slightly increased resorption
      rate (12 (9) v 3 (5)% in controls) and only a slight and statistically non
      significant decrease in mean (SD) embryo and placental weights (1134 (188) and
      136 (11) mg respectively). CONCLUSIONS: The results confirm the induction of
      pathogenic anticardiolipin antibodies by immunisation with serum anticardiolipin,
      dysregulating the idiotypic network, and point to the higher pathogenic potential
      of serum IgG v IgM anticardiolipin antibodies.

PMID- 8257212
TI  - Effects of methotrexate on glycosaminoglycan production by scleroderma
      fibroblasts in culture.
AB  - OBJECTIVE: To determine the effects of increasing concentrations of methotrexate
      on the proliferation and glycosaminoglycan (GAG) synthesis of cultured dermal
      fibroblasts from patients with scleroderma. METHODS: Cultured dermal fibroblasts
      from nine patients with scleroderma and nine normal volunteers were grown for 72
      hours in media containing various concentrations of methotrexate. The GAG
      synthesis in each cell was measured after incubating the fibroblasts with
      [3H]glucosamine and [35S]sulphate. RESULTS: A negative correlation was found
      between the concentration of methotrexate and numbers of fibroblasts from
      patients with scleroderma and normal controls. A positive correlation was found
      between GAG synthesis in each cell, as measured by [3H]glucosamine and
      [35S]sulphate incorporation, and increasing methotrexate concentrations in
      fibroblasts from patients with scleroderma and normal controls. CONCLUSIONS:
      These data indicate increased GAG synthesis in scleroderma and normal fibroblasts
      with increasing concentrations of methotrexate. Therefore the reported beneficial
      effect of methotrexate on skin fibrosis in scleroderma is most probably not the
      result of direct inhibition of GAG synthesis by fibroblasts.

PMID- 8257213
TI  - Multiallelic polymorphism of the cartilage collagen gene: no association with
      osteoarthrosis.
AB  - OBJECTIVES: To determine whether any of the type II collagen alleles are
      associated with generalised osteoarthrosis or osteoarthrosis of the finger joints
      in the genetically isolated Finnish population. METHODS: Two patient cohorts with
      evidence for only primary osteoarthrosis and a cohort of healthy control subjects
      were selected from the Helsinki University Central Hospital and the Rheumatism
      Foundation Hospital in Finland. Forty one patients with primary generalised
      osteoarthrosis, 49 patients with osteoarthrosis of the finger joints, and 48
      control subjects were included. Two markers of the type II collagen gene, a PvuII
      polymorphism and a VNTR polymorphism, were analysed from each subject. RESULTS:
      Four different alleles of the VNTR marker were observed and the relative risks
      associated with the different VNTR alleles varied between 0.39 and 1.24 among the
      patients with generalised osteoarthrosis and between 0.67 and 2.33 among the
      patients with osteoarthrosis of the finger joints. The PvuII polymorphism
      detected two different alleles and the associated relative risks were 0.82 and
      1.82 for the patients with generalised osteoarthrosis, and 1.04 and 0.96 for the
      patients with osteoarthrosis of the finger joints. CONCLUSIONS: A major
      predisposing allele of the type II collagen gene as the causative factor for
      osteoarthrosis could be excluded in this population. A spectrum of mutations
      associated with different alleles of this gene could not be excluded, however.
      Further, these two forms of cartilage disease can be caused by gene defects with
      reduced penetrance and the effect of such an allele is easily masked under the
      high frequency of normal alleles.

PMID- 8257214
TI  - The role of T cells in rheumatoid arthritis.

PMID- 8257215
TI  - Occurrence of arthritis in hyperimmunoglobulinaemia D.

PMID- 8257216
TI  - Erythema induratum and pulmonary tuberculosis.

PMID- 8257217
TI  - CREST syndrome with pericardial but not peripheral calcinosis.

PMID- 8257218
TI  - Surgical treatment of pulmonary metastases. Where do we stand?

PMID- 8257219
TI  - Development and treatment of pulmonary metastases in adult patients with
      extremity soft tissue sarcoma.
AB  - OBJECTIVE: The authors reviewed a series of adult patients with extremity soft
      tissue sarcoma to determine the incidence of pulmonary metastases and outcome
      after treatment. METHODS: Of 716 patients admitted between January 1983 and
      December 1990, 135 (19%) had isolated pulmonary metastases as the initial site of
      distant recurrence. Fifty-eight percent (78 of 135) of the patients were treated
      surgically, and 83% of them had their tumors completely resected. RESULTS: The
      median survival after complete resection was 19 months; incomplete resection, 10
      months; and no operation, 8 months (p = 0.005). The 3-year survival rate after
      complete resection was 23%, compared with a 2% rate (1 of 57) in those treated
      nonsurgically (p < 0.001). Factors associated with an increased risk of pulmonary
      metastases included high tumor grade, tumor size greater than 5 cm, lower
      extremity site, and histologic type (spindle cell, tendosynovial, and
      extraskeletal osteosarcoma). Factors associated with complete resectability were
      the histologic types of spindle cell and extraskeletal osteosarcoma. CONCLUSIONS:
      Complete surgical resection remains the only possibility for cure from pulmonary
      metastases in soft tissue sarcoma; however, only 11% of the 19% of patients with
      an extremity sarcoma whose first distant recurrence is in the lung will be alive
      at 3 years, despite therapy. Complete resection and the development of more
      effective adjuvant treatments are imperative to improve outcome for this group of
      patients.

PMID- 8257220
TI  - It can be fixed, but should it be?

PMID- 8257221
TI  - Glutamine and cancer.
AB  - OBJECTIVE: This overview on glutamine and cancer discusses the importance of
      glutamine for tumor growth, summarizes the alterations in interorgan glutamine
      metabolism that develop in the tumor-bearing host, and reviews the potential
      benefits of glutamine nutrition in the patient with cancer. SUMMARY BACKGROUND
      DATA: Glutamine is the most abundant amino acid in the blood and tissues. It is
      essential for tumor growth and marked changes in organ glutamine metabolism are
      characteristic of the host with cancer. Because host glutamine depletion has
      adverse effects, it is important to study the regulation of glutamine metabolism
      in cancer and to evaluate the impact of glutamine nutrition in the tumor-bearing
      state. METHODS: Data from a variety of investigations on glutamine metabolism and
      nutrition related to the host with cancer were compiled and summarized. RESULTS:
      Numerous studies on glutamine metabolism in cancer indicate that many tumors are
      avid glutamine consumers in vivo and in vitro. As a consequence of progressive
      tumor growth, host glutamine depletion develops and becomes a hallmark. This
      glutamine depletion occurs in part because the tumor behaves as a "glutamine
      trap" but also because of cytokine-mediated alterations in glutamine metabolism
      in host tissues. Animal and human studies that have investigated the use of
      glutamine-supplemented nutrition in the host with cancer suggest that
      pharmacologic doses of dietary glutamine may be beneficial. CONCLUSIONS:
      Understanding the control of glutamine metabolism in the tumor-bearing host not
      only improves the knowledge of metabolic regulation in the patient with cancer
      but also will lead to improved nutritional support regimens targeted to benefit
      the host.

PMID- 8257222
TI  - Incidence of gross and microscopic carcinoma in specimens from patients with
      breast cancer after re-excision lumpectomy.
AB  - OBJECTIVE: The aims of this study were to quantify the amount of the residual
      carcinoma in re-excision lumpectomy specimens and retrospectively analyze the
      relationship between clinical parameters and the characteristics of the primary
      excision to these quantities of the residual tumor. SUMMARY BACKGROUND DATA:
      Because complete gross surgical excision of the primary tumor is important in
      minimizing local recurrence in women undergoing breast conservation therapy, re
      excision of the initial biopsy site is commonly practiced when the initial
      primary tumor excision shows inadequate or undeterminable margins. Several
      studies have reported a significant proportion of re-excision specimens to
      contain residual tumor (32% to 63%), but to the authors' knowledge, none have
      quantified the amount of residual tumor. METHODS: The authors reviewed 192 re
      excisions retrospectively to quantify the amount of residual carcinoma and
      correlate the quantities with the characteristics of the primary tumor resection.
      RESULTS: No tumor was found in 105 (54.7%) specimens, 46 (23.9%) had minimal
      microscopic disease, 23 (12.0%) had extensive microscopic disease, and 18 (9.4%)
      had gross residual cancer. Characteristics significantly associated with the
      quantity of residual disease included clinical tumor stage (T stage), pathologic
      T stage, and the margin status of the primary excision. The majority (62.1%) of
      re-excision specimens containing residual carcinoma had an invasive component.
      CONCLUSIONS: It was concluded that re-excision lumpectomy yields an important
      number of patients with residual carcinoma and that characteristics of both the
      primary tumor and primary excision significantly predict the quantity of residual
      cancer in the specimen. In addition, these results support the policy of
      performing re-excision for patients with inadequate or undeterminable margins for
      the primary excision.

PMID- 8257223
TI  - The effect of endogenous cholecystokinin released by bombesin and trypsin
      inhibitor on the regeneration of the pancreas.
AB  - OBJECTIVE: This study examined the effects of endogenous cholecystokinin (CCK)
      released by bombesin and FOY-305 (a synthetic inhibitor of trypsin on pancreatic
      regeneration in rats). SUMMARY BACKGROUND DATA: Trophic gut hormones (CCK and
      bombesin) stimulate the growth of the normal rat pancreas. However, the influence
      of endogenous gut hormones on pancreatic regeneration is unclear. METHODS: Male
      Fisher rats (n = 6 to 8 per group) were fed a protein-free diet and given
      ethionine (700 mg/kg intraperitoneally daily) for 8 to 9 days to induce
      degeneration of the pancreas. Regeneration was stimulated by giving the rats a
      regular chow diet. The effects of bombesin (10 micrograms/kg three times a day
      for 7 days) or FOY-305 (200 mg/kg daily for 8 days) on the process of
      regeneration were examined. RESULTS: At the end of the degeneration phase, there
      was near-total destruction of pancreatic acinar cells. Both bombesin and FOY-305
      stimulated pancreatic regeneration. Growth measurements (weight and total content
      of DNA and protein) were significantly increased (p < 0.05) in the bombesin- and
      FOY-305-treated rats compared with controls. Histologic examination revealed
      widespread repopulation of the pancreas with acinar cells in the bombesin- and
      FOY-305-treated groups. The stimulating effects of both bombesin and FOY-305 on
      pancreatic regeneration were blocked completely by the CCK-receptor antagonist L
      364,718. Growth measurements were not significantly increased in the groups of
      control rats or rats given L-364,718 alone. CONCLUSIONS: These results show that
      bombesin and FOY-305 significantly stimulated pancreatic regeneration. Because
      the stimulating effects of bombesin and FOY-305 on regeneration were blocked by
      the specific CCK-receptor antagonist L-364,718, it was concluded that this effect
      was mediated by endogenous CCK.

PMID- 8257224
TI  - Selective management of gastroschisis according to the degree of visceroabdominal
      disproportion.
AB  - OBJECTIVE: This study analyzed the factors influencing the postoperative results
      after the repair of gastroschisis defects during the past 27 years. SUMMARY
      BACKGROUND DATA: The clinical results after the repair of gastroschisis abdominal
      defects have improved appreciably during the past 25 years, with the long-term
      survival rate in most large children's centers currently being approximately 90%.
      The improvement in survival has been largely attributed to advances in
      perioperative care, frequent use of parenteral nutrition, and better techniques
      of surgical repair. METHODS: Between 1965 and 1992, 84 infants with gastroschisis
      underwent surgical repair. The management of 52 infants after 1979 was compared
      with that of 32 during the previous 14 years. Associated anomalies were present
      in 29%. The average birth weight was 2412 g. In 31%, primary fascial closure was
      performed. In another 31% with moderate visceroabdominal disproportion (VAD), a
      silastic chimney was used initially, and complete repair was performed at a
      second operation. For 25% who had severe VAD, more than two operative
      reconstructions were necessary. Seven of 52 infants with moderate VAD underwent
      initial skin-flap closure and secondary repair within 12 days. RESULTS: Almost
      all complications (27%) and deaths (4%) occurred in infants with severe VAD and
      were largely unrelated to associated malformations or birth weight. The length of
      postoperative mechanical ventilation, need for parenteral nutrition, need for
      multiple operations, and length of hospitalization were all directly related to
      the severity of the VAD. CONCLUSIONS: Complete repair of gastroschisis at the
      initial operation is the optimal goal; however, the severity of VAD has permitted
      this approach in only one third of patients in this study. Delayed repair with a
      silastic chimney and one or more reconstructive procedures has provided excellent
      long-term survival with low morbidity and mortality rates. Although skin-flap
      closure is no longer used initially, this technique has been helpful for the
      residual defect in infants with severe VAD who have had multiple silon chimney
      repairs (Applied Biomaterial, Silverdale, WA).

PMID- 8257225
TI  - Drainage after elective hepatic resection. A randomized trial.
AB  - OBJECTIVE: This prospective randomized study determined the influence of closed
      suction drainage on the incidence of postoperative complications after elective
      hepatic resection. SUMMARY BACKGROUND DATA: Routine drainage is no longer
      advocated after several intra-abdominal surgical procedures. METHODS: A series of
      81 patients who underwent elective hepatic resection were randomly allocated to
      either a nondrainage group (n = 39) and a drainage group with closed-suction
      drainage (n = 42). Indications for resection were 42 benign lesions and 39
      malignant tumors, including 19 with cirrhosis. Major hepatic resection was
      performed in 25 patients and minor resection, in 56. All patients underwent
      ultrasonography with puncture for bacteriologic cultures of all fluid collections
      within the first 5 postoperative days. RESULTS: One patient died in each group.
      Ultrasonography found a significantly higher rate of subphrenic collections in
      the drainage group compared with the nondrainage group (respectively, 36% vs.
      15%, p < 0.05). These collections were more frequently infected in the drainage
      group (n = 6) than in the nondrainage group (n = 2). After major liver resection,
      the rate of intra-abdominal postoperative complications (i.e., subphrenic fluid
      collections, hematomas, and bilomas) was similar between the two groups.
      CONCLUSIONS: Minor liver resection is safer without drainage. Major liver
      resection can be performed with or without abdominal drainage.

PMID- 8257226
TI  - Rectal wall contractility in healthy subjects and in patients with chronic severe
      constipation.
AB  - OBJECTIVE: The aim of this study was to identify differences in rectal wall
      contractility between healthy volunteers and patients with chronic severe
      constipation. SUMMARY BACKGROUND DATA: Whether motor function of the rectum
      contributes to slow-transit constipation is unknown. Measurements of rectal
      contractility have been performed traditionally with perfused catheters or
      microtransducers. The rectal barostat is a new technique that quantifies the
      volume of air within an infinitely compliant intrarectal bag maintained at
      constant pressure; decreases in bag volume therefore reflect increases in rectal
      muscular contractility (tone). Increases in volume reflect decreased
      contractility. METHODS: Fifteen healthy volunteers (ten women and five men; mean
      age, 36 years) and eight patients (seven women and one man; mean age, 44 years)
      were studied. Barostat recordings were made for 1 hour before and after a meal.
      Randomly, neostigmine (0.5 mg) or glucagon (1 unit) was then given intravenously.
      After 1 hour, the other medication was given. RESULTS: The fasting rectal volume
      was similar in the patient and control groups (113 +/- 7 mL vs. 103 +/- 4 mL,
      respectively; p > 0.05). Compared with controls, constipated patients had a
      significantly lower reduction in rectal volume after a meal (constipated, 35 +/-
      8% vs. controls, 65 +/- 7%; p < 0.05) and after neostigmine administration
      (constipated, 39 +/- 6% vs. controls, 58 +/- 6%; p < 0.05). Moreover, constipated
      patients had a smaller increase in rectal volume after glucagon administration
      than did controls (28 +/- 6% vs. 64 +/- 18%, respectively; p < 0.05. CONCLUSIONS:
      Changes in rectal wall contractility in response to feeding, a cholinergic
      agonist, and a smooth muscle relaxant were decreased in constipated patients.
      These findings suggest that an abnormality of rectal muscular wall contractility
      is present in constipated patients.

PMID- 8257227
TI  - Cytokine patterns in patients after major vascular surgery, hemorrhagic shock,
      and severe blunt trauma. Relation with subsequent adult respiratory distress
      syndrome and multiple organ failure.
AB  - OBJECTIVE: This study investigates the course of serum cytokine levels in
      patients with multiple trauma, patients with a ruptured abdominal aortic aneurysm
      (AAA), and patients undergoing elective AAA repair and the relationship of these
      cytokines to the development of adult respiratory distress syndrome (ARDS) and
      multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Severe tissue trauma,
      hemorrhagic shock, and ischemia-reperfusion injury are pathophysiologic
      mechanisms that may result in an excessive uncontrolled activation of
      inflammatory cells and mediators. This inflammatory response is thought to play a
      key role in the development of (remote) cell and organ dysfunction, which is the
      basis of ARDS and MOF. METHODS: The study concerns 28 patients with multiple
      trauma, 20 patients admitted in shock because of a ruptured AAA, and 18 patients
      undergoing elective AAA repair. Arterial blood was serially sampled from
      admission (or at the start of elective operation) to day 13 in the intensive care
      unit, and the serum concentrations of tumor necrosis factor-alpha (TNF-alpha),
      interleukin (IL)-1 beta, and IL-6 were determined. RESULTS: Twenty-two patients
      died, 15 within 48 hours and 7 after several weeks, as a result of ARDS/MOF. At
      hospital admission and after 6 hours, these nonsurvivors had significantly higher
      plasma TNF-alpha and IL-1 beta levels than did the survivors. At the same
      measuring points, TNF-alpha and IL-1 beta were significantly more elevated in
      patients with ruptured AAA than in traumatized patients. However, IL-6 was
      significantly higher in the traumatized patients. In 10 patients, ARDS/MOF
      developed, and 41 had an uncomplicated course in this respect. Those with
      ARDS/MOF exhibited significantly different cytokine patterns in the early
      postinjury phase. TNF-alpha and IL-1 beta levels were higher mainly on the first
      day of admission; IL-6 concentrations were significantly elevated in patients
      with ARDS/MOF from the second day onward. The latter cytokine showed a good
      correlation with the daily MOF score during the whole 2-week observation period.
      CONCLUSIONS: In the early postinjury phase, higher concentrations of these
      cytokines are associated, not only with an increased mortality rate, but also
      with an increased risk for subsequent ARDS and MOF. These data therefore support
      the concept that these syndromes are caused by an overwhelming autodestructive
      inflammatory response.

PMID- 8257228
TI  - A prospective trial of subxiphoid pericardiotomy in the diagnosis and treatment
      of large pericardial effusion. A follow-up report.
AB  - OBJECTIVE: This study was designed to determine the cause of large pericardial
      effusions and evaluate the efficacy of subxiphoid pericardiotomy. SUMMARY
      BACKGROUND DATA: Despite great advances in the techniques used to diagnose
      pericardial effusions, much controversy remains concerning their cause and the
      optimal treatment of these effusions. METHODS: In a prospective consecutive case
      series, 57 patients underwent a thorough preoperative evaluation followed by a
      subxiphoid pericardiotomy. All tissue and fluid was exhaustively evaluated.
      Postoperatively, all patients were followed for a least 1 year. RESULTS: Surgery
      was performed under local anesthesia in 77% of patients, and the complications of
      surgery were minimal. Pericardial tissue and fluid established or aided in
      establishing a diagnosis in 81% of patients. Infection and malignancy were the
      leading causes; the condition in only 4 patients remained undiagnosed. Follow-up
      revealed recurrent effusion in nine (16%) patients, but only five (9%) required
      further surgery. The mortality rate at 30 days was 12%, and at 1 year, it was
      37%. Fourteen of the 21 deaths occurred in patients with malignancies.
      CONCLUSIONS: These data show that the cause of most large pericardial effusions
      can be determined by a thorough evaluation accompanied by subxiphoid
      pericardiotomy. In addition, subxiphoid pericardial biopsy and window creation is
      safe and effective in the treatment of these effusions.

PMID- 8257229
TI  - Traumatic diaphragmatic hernia. Occult marker of serious injury.
AB  - OBJECTIVE: Recent experience with traumatic diaphragmatic hernias at the
      Massachusetts General Hospital was reviewed to identify pitfalls in the diagnosis
      and treatment of this injury. SUMMARY BACKGROUND DATA: Traumatic diaphragmatic
      disruption is a common injury and a marker of severe trauma. It occurs in 5% of
      hospitalized automobile accident victims and 10% of victims of penetrating chest
      trauma. Numerous reports describe splenic rupture in 25% of patients with blunt
      diaphragmatic rupture, liver lacerations in 25%, pelvic fracture in 40%, and
      thoracic aortic tears in 5%. Diaphragmatic rupture is a predictor of serious
      associated injuries which, unfortunately, is itself often occult. METHODS: A
      chart review of all patients admitted to the Trauma Service with traumatic
      diaphragmatic hernias was undertaken for the period of January 1982 to June 1992.
      RESULTS: Data on 68 patients sustaining blunt (n = 25) and penetrating (n = 43)
      diaphragmatic rupture or laceration were presented. The diagnosis was made
      preoperatively in only 21 (31%). Associated injuries were frequent in those
      injured by either blunt or penetrating trauma. Sixty-six patients underwent
      repair, 54 (82%) through a laparotomy alone and 12 (18%) with the addition of a
      thoracotomy. There were five (7.4%) deaths that were caused by coagulopathy,
      hemorrhagic shock, multisystem organ failure, and pulmonary embolism.
      Complications were twice as frequent in the blunt-trauma group and included
      abscess, pneumonia, and the sequelae of closed head injuries. CONCLUSIONS: The
      recognition of diaphragmatic rupture is important because of the frequency and
      severity of associated injuries. The difficulties in reaching the diagnosis
      require an aggressive search in patients at risk.

PMID- 8257230
TI  - Macrophage elimination increases bacterial translocation and gut-origin
      septicemia but attenuates symptoms and mortality rate in a model of systemic
      inflammation.
AB  - OBJECTIVE: The central question tested in this study was whether
      dichloromethylene-diphosphonate (CL2MDP) liposome-mediated elimination of hepatic
      and splenic macrophages would influence zymosan-induced bacterial translocation
      and the zymosan-induced generalized inflammatory response. SUMMARY BACKGROUND
      DATA: Both an uncontrolled activation of macrophages and the loss of intestinal
      barrier function have been implicated in the development of adult respiratory
      distress syndrome and multiple organ failure. METHODS: Macrophage elimination was
      accomplished by intravenous injection of 200 microL of CL2MDP-liposome
      suspension. Control mice received an intravenous injection of 200 microL of
      phosphate-buffered saline. Two days later, the animals were challenged
      intraperitoneally with zymosan suspended in paraffin to determine a dose-response
      curve (0.1, 0.5, or 1.0 mg/g body weight). Twenty-four hours after zymosan
      challenge, signs of systemic stress were determined, and bacterial translocation
      to the mesenteric lymph node, liver, spleen, and blood was measured. A separate
      mortality study was performed with a dose of 1.0 mg/g of zymosan suspension.
      RESULTS: The incidence of the systemic spread of bacteria was significantly
      increased in the macrophage-depleted mice. Although systemic bacterial
      translocation was promoted by macrophage elimination, the systemic toxic response
      was significantly decreased in all macrophage-depleted groups (p < or = 0.01).
      The 12-day mortality rate was 0% in the macrophage-depleted groups and 27% in the
      control group (p = 0.05). CONCLUSIONS: The lethal and toxic effects of zymosan
      appear to be related more to the excessive activation of macrophages than to the
      systemic spread of bacteria.

PMID- 8257232
TI  - Community participation in vector-borne disease control.
AB  - Because vertical approaches, such as insecticidal house-spraying, to vector
      control problems have not been very successful in many instances in reducing the
      incidence of diseases such as malaria and Chagas, combined with the fact that
      there have been resurgences of some diseases, greater attention has been focused
      on 'bottom-up'-type control strategies. However, many attempts to actively
      involve the community in reducing its risks of becoming ill have met with
      failure. It has usually proved difficult to motivate communities into action, but
      there have been some successes, although it is generally too early to know
      whether such successes can be sustained. Apart from greater efforts to educate
      communities to disease risks and disease prevention methods, sociologists and
      anthropologists argue that we need to listen more to the people and pay greater
      attention to their beliefs and customs. The present paper discusses the problems
      of introducing self-help methods to minimize vector-borne disease transmission,
      and reviews the successes and failures of this approach.

PMID- 8257231
TI  - Opposite effects of interleukin-2 on normal and transfusion-suppressed healing of
      experimental intestinal anastomoses.
AB  - OBJECTIVE: This study was done to investigate whether administration of
      interleukin-2 (IL-2) can abrogate the negative effects of blood transfusions on
      anastomotic healing. SUMMARY BACKGROUND DATA: Recently, the authors showed that
      blood transfusion severely impairs anastomotic repair and significantly increases
      the susceptibility to intra-abdominal septic complications in rats. It has been
      reported that blood transfusions suppress IL-2 production and that IL-2 may
      stimulate wound healing. METHODS: Lewis rats underwent resection and anastomosis
      of both the ileum and colon. Subsequently, they received either 3 mL of saline
      (control and IL-2 groups) or 3 mL of blood from brown Norway donors (transfusion
      and transfusion/IL-2 groups) intravenously. From the operation onward, the
      animals in the IL-2 and transfusion/IL-2 groups received daily injections of 5.4
      x 10(5) IU of IL-2 in dextrose solution subcutaneously; the rats in the other
      groups received only the dextrose solution. The animals were killed 3 or 7 days
      after the operation and examined for septic complications and anastomotic repair.
      RESULTS: Transfusion led to an enhanced incidence of anastomotic abscesses, which
      was almost completely abrogated after IL-2 administration. The anastomotic
      strength was consistently and significantly reduced after transfusion. Seven days
      after surgery, the anastomotic strength was completely restored by IL-2
      treatment. For instance, the average bursting pressure (+/- the standard
      deviation) of the ileal anastomoses in the control, transfusion, and
      transfusion/IL-2 groups were 86 +/- 15, 32 +/- 8,* and 63 +/- 10 mmHg* [symbol:
      see text] on day 3 and 293 +/- 36, 227 +/- 16,* and 299 +/- 19 mmHg on day 7,
      respectively (where * = significant vs. control group and [symbol: see text] =
      significant vs. transfusion group). In addition, IL-2 administration elevated the
      anastomotic hydroxyproline content, which was significantly decreased by
      transfusion alone, to the level found in the control group. The administration of
      IL-2 to control animals resulted unexpectedly in a significant reduction in
      anastomotic strength. CONCLUSIONS: Exogenous IL-2 reverses the negative effects
      of blood transfusions on anastomotic repair, but it impairs healing under normal
      conditions.

PMID- 8257233
TI  - In vitro sensitivity of southern African isolates of Plasmodium falciparum to
      halofantrine.
AB  - Twenty southern African isolates of Plasmodium falciparum and a 'control' Gambian
      strain were tested in vitro for their sensitivity to halofantrine. The
      concentration required to inhibit 50% of parasite growth, the IC50, ranged from
      0.039 to 15.000 nmol/litre, with a mean of 4.619 nmol/litre. These IC50 values
      were comparable with those obtained in studies carried out in West Africa but
      were higher than the IC50 of South-East Asian isolates. All 21 isolates examined
      in the present study had minimum inhibitory concentrations (MIC) of 32 nmol/litre
      or less, with a median MIC value of 8 nmol/litre. Halofantrine was equally active
      against chloroquine-sensitive and chloroquine-resistant isolates and was also
      active against pyrimethamine-resistant strains. Indications are that this drug
      would be suitable for the treatment of P. falciparum malaria in the southern
      African region.

PMID- 8257234
TI  - Albendazole therapy of hydatid disease: 2-year follow-up of 40 cases.
AB  - Forty patients with 63 Echinococcus granulosus cysts affecting different sites
      were treated with albendazole and have been followed up for at least 24 months
      from completion of therapy. Twenty-one patients (53%) with 37 cysts (59%) showed
      evidence of healing. The criteria and pattern of healing are outlined. The most
      serious complication of albendazole therapy was hepatoxic jaundice, which
      occurred in 5% of patients. Recurrence during the observation period was
      encountered in 9.5% of patients with a positive response. It is suggested that
      patients suffering from uncomplicated hydatid disease should be given the benefit
      of a trial course of albendazole therapy, before surgery is undertaken.

PMID- 8257235
TI  - Reduction of filaritic lymphoedema and elephantiasis by 5,6 benzo-alpha-pyrone
      (coumarin), and the effects of diethylcarbamazine (DEC).
AB  - Chronic filaritic lymphoedema and elephantiasis, in India, were treated orally
      with 5,6 benzo-alpha-pyrone (56 BaP; 1,2 benzo-alpha-pyrone; coumarin) in a
      double-blind, randomized, matched-group trial. Each group finally contained 40-55
      patients. Patients were observed for about 2 years (ranging from 6 to 45 months,
      with 75% completing the 2 years). The 56 BaP slowly, but very significantly (P <
      0.0001), reduced all grades of lymphoedema and elephantiasis. Two thirds of the
      oedema was lost by grade 2 over 2 years. Grades 3 to 5 were reduced by a fifty
      over that time. The greater the initial oedema, the greater was its rate of
      resolution. A slowly worsening condition thus became a slowly improving one.
      Slowness has its advantages: compression stockings, that are impractical in hot,
      wet or dirty conditions, are not necessary. The slowly remodelling fibrous
      tissue, while lessening in amount, is still able to hold the tissues together.
      The 56 BaP considerably improved many symptoms and complications, particularly
      bursting-pains, inflammation and ulcers. It is cheap and of very low toxicity.
      Diethylcarbamazine (DEC) was studied with and without 56 BaP. DEC alone gave some
      reduction of the oedema, but this was much smaller than that with 56 BaP. It
      considerably worsened the reductions by 56 BaP, while 56 Bap slightly improved
      those by DEC and reduced the fever caused by DEC. Together, they reduced feelings
      of swelling and bursting-pain, fungal infections, lymphangitis and lymphadenitis
      more than when used alone.

PMID- 8257236
TI  - Ophthalmomyiasis externa caused by Oestrus ovis L. in the Ajloun area of northern
      Jordan.
AB  - During the years 1990-1991 17 cases of ophthalmomyiasis externa due to the sheep
      nasal botfly, Oestrus ovis, were reported from the Ajloun area in northern
      Jordan. Symptoms included mild to severe conjunctivitis, cellulitis, lacrimation
      and conjunctival hyperaemia. All cases were among males, and they occurred either
      from April to July or from September to November.

PMID- 8257237
TI  - The gonotrophic status and diel pattern of entry to outdoor oviposition sites of
      female Aedes aegypti (L.) (Diptera: Culicidae).
AB  - Experimental observations, made outdoors during the dry and wet seasons in
      Trinidad, confirm earlier findings regarding the diel pattern of entry to
      ovitraps and oviposition there and the taking of more than one bloodmeal during a
      single gonotrophic cycle. For 6-h but not for 6-h exposure periods, significantly
      more eggs were laid in the morning peak during the dry season than during the wet
      season. At the study site females were encountered singly, and only in ovitraps
      that contained eggs. With regard to their gonotrophic status, we conclude that,
      when captured, most and probably all of these females were about to oviposit,
      were in the process of ovipositing or had just finished ovipositing, and moreover
      that the laid eggs in an ovitrap were usually the product of a single female.
      There was no indication that females normally enter an ovitrap in the early
      afternoon 2 or more hours before ovipositing there.

PMID- 8257238
TI  - Cuticular hydrocarbon discrimination/variation among strains of the mosquito,
      Anopheles (Cellia) stephensi Liston.
AB  - Cuticular lipids were removed from adult female Anopheles stephensi Liston and
      the hydrocarbons present were separated and quantified by gas chromatography.
      Comparison was made between the hydrocarbons of four An. stephensi strains: Russ,
      sensitive to DDT and malathion and originally isolated in the former U.S.S.R.;
      Beech, a DDT-resistant Indian strain with high sensitivity to Plasmodium species;
      St Mal, a strain from Pakistan shown to be resistant to malathion; and Iraq, a
      DDT-susceptible strain from Iraq. Discriminant analysis indicated that the four
      groups were distinct and that, on average, 78% of the population could be
      separated on the basis of the quantities of some of the cuticular hydrocarbons.
      The profiles of Beech and Russ or Russ and St Mal could be separated in 98% of
      the cases. There was reduced segregation between the profiles of St. Mal and
      Iraq, suggesting greater similarity in the hydrocarbons of these two strains. The
      usefulness of cuticular hydrocarbon in determining species relationships is
      discussed.

PMID- 8257239
TI  - Use of the median process of the pygophore in the identification of Rhodnius
      nasutus, R. neglectus, R. prolixus and R. robustus (Hemiptera: Reduviidae).
AB  - The morphometrics of the median process of the male pygophore of four species of
      blood-sucking bugs (Rhodnius prolixus, R. robustus, R. nasutus and R. neglectus)
      were compared using one-way analysis of variance. Although there were no
      significant differences in the pygophoral patterns within the R. nasutus-R.
      neglectus or R. prolixus-R. robustus species pairs, there were clear-cut
      differences between them; the median process of R. nasutus-R. neglectus is stout
      and subtriangular whereas that of R. prolixus-R. robustus is more narrow and
      elongated. The basal width of the process, classically used to separate R.
      robustus from R. prolixus and R. nasutus from R. neglectus, seems to have little
      taxonomic value. Other characters which have been assumed to be species-specific
      should be subjected to a similar quantitative analysis.

PMID- 8257240
TI  - Polyparasitism on the Kenya coast. 2. Spatial heterogeneity in parasite
      distributions.
AB  - In a parasitological survey of people living in 20 clusters of homes within 50 km
      of Kilifi, Coast Province, Kenya, internally age-standardized prevalences showed
      considerable variation. While this was correlated, in part, with the steep
      gradients of environmental variables related to distance from the coast,
      considerable residual variation remained. Indeed, isopleths for parasite
      prevalence frequently transected those for environmental parameters. It is
      concluded that broad environmental parameters are limited in their predictive
      value for determining parasite presence or prevalence; a study of the causes of
      major differences between villages in the same environment might indicate
      relatively simple control measures.

PMID- 8257241
TI  - Clinical and immunological study of schistosomal myeloradiculopathy.

PMID- 8257242
TI  - Avidin-biotin enzyme-linked immunosorbent assay (AB-ELISA) for the detection of
      bancroftian filariasis.

PMID- 8257243
TI  - Haemagglutinin activity in tick (Rhipicephalus appendiculatus) haemolymph and
      extracts of gut and salivary gland.

PMID- 8257244
TI  - Typing of Simulium using mitochondrial DNA PCR products with restriction
      endonuclease digestion.

PMID- 8257245
TI  - Storage time of ELISA bloodmeal test kits.

PMID- 8257246
TI  - The end of life and the goals of medicine.

PMID- 8257247
TI  - Patient refusal of hydration and nutrition. An alternative to physician-assisted
      suicide or voluntary active euthanasia.

PMID- 8257248
TI  - How much is too much? Advising patients about safe levels of alcohol consumption.
AB  - United States physicians are increasingly encouraged to advise patients about
      health-related behaviors, such as smoking, but there is minimal discussion in the
      US medical literature about the need to advise patients about safe levels of
      alcohol consumption. Several factors likely contribute to this lack of focus on
      safe drinking practices. These include the complex relationship between drinking
      and health, limitations in the available epidemiologic data, misinterpretation of
      the disease model of alcoholism, and physician attitudes. Nevertheless,
      epidemiologic evidence clearly relates increasing levels of alcohol consumption
      to increased morbidity and mortality, and research has shown that physician
      advice can reduce both alcohol consumption and alcohol-related problems. We
      propose that physicians thoroughly assess patients' alcohol consumption and
      advise patients who drink about safe levels of consumption.

PMID- 8257249
TI  - A review of common errors in the indirect measurement of blood pressure.
      Sphygmomanometry.
AB  - There are three sources of error in the indirect measurement of blood pressure:
      (1) observer bias, (2) faulty equipment, and (3) failure to standardize the
      techniques of measurement. This article examines each area extensively, discusses
      the cumulative effect of these errors on the accuracy of indirect blood pressure
      measurement, and reviews the recommendations for proper indirect measurement of
      blood pressure.

PMID- 8257250
TI  - Predicting the outcomes of human immunodeficiency virus infection. How well are
      we doing.
AB  - An important determinant of patient outcomes is illness severity, which must be
      classified to guide clinical decision making and evaluate the effectiveness of
      diagnostic and therapeutic interventions. Currently, no widely accepted framework
      for grading illness severity in human immunodeficiency virus-infected patients
      exists. The best known classification systems for human immunodeficiency virus
      infection (Centers for Disease Control and Prevention; Walter Reed) are not based
      on illness severity, and provide stages that are not all inclusive so that a
      large number of persons cannot be classified (Walter Reed). Although much
      previous research has focused on individual prognostic factors (oral thrush, CD4
      cell count, serum beta 2-microglobulin), little attention has been given to
      incorporating these factors into illness severity scales that are easy to use in
      clinical settings. In addition, despite the progressive functional disability of
      human immunodeficiency virus-infected individuals, few of the existing approaches
      to illness severity classification have examined the contribution of functional
      status. We urge investigators to develop clinically sensible severity scales that
      are easy to use. Such scales will considerably improve existing approaches that
      tend to rely solely on the CD4 cell count and do not take into account the known
      prognostic effects of other variables.

PMID- 8257251
TI  - Prevalence of fatigue and chronic fatigue syndrome in a primary care practice.
AB  - BACKGROUND: Our goals were to determine the prevalence of unusual, debilitating
      fatigue and the frequency with which it was associated with the chronic fatigue
      syndrome (CFS) or other physical or psychological illness in an outpatient clinic
      population. METHODS: We prospectively evaluated a cohort of 1000 consecutive
      patients in a primary care clinic in an urban, hospital-based general medicine
      practice. The study protocol included a detailed history, physical examination,
      and laboratory and psychiatric testing. RESULTS: Five patients who came because
      of CFS studies were excluded. Of the remaining 995, 323 reported fatigue, and 271
      (27%) complained of at least 6 months of unusual fatigue that interfered with
      their daily lives. Of the 271, self-report or record review revealed a medical or
      psychiatric condition that could have explained the fatigue in 186 (69%). Thus,
      85 (8.5%) of 995 patients had a debilitating fatigue of at least 6 months'
      duration, without apparent cause. Of these patients, 48 refused further
      evaluation, and 11 were unavailable for follow-up; 26 completed the protocol.
      Three of the 26 were hypothyroid, and one had a major psychiatric disorder. Of
      the remaining 22 patients, three met Centers for Disease Control and Prevention
      criteria for CFS, four met British criteria, and 10 met the Australian case
      definition. The point prevalences of CFS were thus 0.3% (95% confidence interval
      [CI], 0% to 0.6%), 0.4% (95% CI, 0% to 0.8%), and 1.0% (95% CI, 0.4% to 1.6%)
      using the Centers for Disease Control and Prevention, British, and Australian
      case definitions, respectively. These estimates were conservative, because they
      assumed that none of the patients who refused evaluation or were unavailable for
      follow-up would meet criteria for CFS. CONCLUSIONS: While chronic, debilitating
      fatigue is common in medical outpatients, CFS is relatively uncommon. Prevalence
      depends substantially on the case definition used.

PMID- 8257252
TI  - The Loyola University lung transplant experience.
AB  - BACKGROUND: We reviewed our experience with isolated lung transplantation at
      Loyola University Medical Center, Maywood, Ill. From April 1990 through June
      1992, 33 lung transplantations for end-stage pulmonary disease were performed (30
      single lung, three bilateral single lung). Recipient diagnoses include chronic
      obstructive pulmonary disease, alpha 1-antiprotease deficiency, pulmonary
      fibrosis, primary pulmonary hypertension, Eisenmenger's syndrome, sarcoidosis,
      cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. METHODS: For
      patients who underwent transplantation for end-stage obstructive airway disease,
      we retrospectively reviewed functional indexes before and after transplantation.
      In addition, the overall survival rate was determined. RESULTS: Successful
      transplantation resulted in a marked improvement in functional capacity. Single
      lung transplantation for end-stage obstructive airway disease resulted in a
      threefold improvement in the 1-second forced expiratory volume, from 0.49 to 1.64
      L. The actual survival for all isolated lung transplant recipients (including
      both single-lung and bilateral single-lung procedures) was 73%, with a 15% 30-day
      mortality. CONCLUSION: Isolated lung transplantation can significantly improve
      functional capacity as well as the quality of life in patients with end-stage
      lung disease.

PMID- 8257253
TI  - Distribution of thrombosis in patients with symptomatic deep vein thrombosis.
      Implications for simplifying the diagnostic process with compression ultrasound.
AB  - BACKGROUND: Two different diagnostic strategies are used to perform compression
      (real-time) ultrasound for the diagnosis of clinically suspected deep-vein
      thrombosis. One is to examine the entire proximal venous system from common
      femoral to distal popliteal vein; the other is a limited examination of only the
      common femoral and the entire popliteal vein. The latter strategy, which is less
      time-consuming and requires less expensive equipment, is based on a strong
      impression from prospective studies using limited compression ultrasound that
      proximal vein thrombi always involve the common femoral or popliteal vein. This
      impression, which is supported by the demonstrated safety at long-term follow-up
      of not treating patients whose limited compression ultrasound is normal at
      presentation and then repeated within the next week, has not been tested in a
      formal study. Therefore, we reviewed a large series of venograms performed in
      consecutive patients with clinically suspected venous thrombosis to determine the
      distribution of venous thrombosis in symptomatic patients. METHODS: Venograms
      were performed using 150 mL of radiographic contrast material. Before the study,
      a panel of experts agreed on the standardized criteria for the assessment of
      venograms. Venograms were adjudicated blindly for the presence of deep vein
      thrombosis and to determine the distribution of proximal vein thrombosis and
      isolated calf-vein thrombosis, the size of proximal thrombi, and whether they
      were occlusive or nonocclusive. Subsequently, the duration of symptoms was
      related to the venographic findings. RESULTS: Five hundred sixty-two venograms
      from consecutive patients with a first episode of clinically suspected deep vein
      thrombosis were adjudicated. Of these, 20 (3.6%) were inadequate for
      interpretation. In the remaining 542, venous thrombosis was demonstrated in 189
      instances (prevalence, 35%; 95% confidence interval, 31% to 39%) and were located
      in the proximal veins in 166 (88%; 95% confidence interval, 82% to 92%)
      venograms. Isolated calf-vein thrombosis was present in the remaining 23 (12%;
      95% confidence interval, 8% to 18%) venograms. Proximal with concurrent calf
      thrombosis was detected in 164 (99%) of the 166 patients. Proximal thrombi
      involved only the popliteal vein in 16 (10%); the popliteal and superficial
      femoral veins in 70 (42%); and the popliteal, superficial, and common femoral
      vein in eight (5%); whereas thrombi involving the entire proximal deep venous
      system were detected in 58 (35%) venograms. Isolated thrombosis of the
      superficial femoral, common femoral, and iliac vein was not observed. Proximal
      venous thrombi were occlusive in 146 (88%) patients. No relation between the
      duration of symptoms and the extent or the occlusiveness of venous thrombi could
      be demonstrated. CONCLUSIONS: Most symptomatic patients have extensive occlusive
      proximal vein thrombosis at the time of presentation. Thrombi isolated to the
      superficial femoral or iliac vein were not observed in this large sample of
      consecutive patients. Our data support the use of the relatively simple,
      inexpensive, and rapid compression ultrasound method that limits the examination
      of the proximal veins to the common femoral and popliteal veins.

PMID- 8257254
TI  - Racial variations in the rates of carotid angiography and endarterectomy in
      patients with stroke and transient ischemic attack.
AB  - BACKGROUND: Carotid endarterectomy is emerging as the treatment of choice for
      patients with symptomatic carotid artery stenosis at low operative risk. We
      sought to determine if racial variations in the rate of carotid angiography and
      endarterectomy exist in the Veteran Affairs health care system among patients who
      are insulated from the cost of their care. METHODS: From a national database of
      all hospitalizations at Veterans Affairs medical centers, we identified a cohort
      of patients with diagnoses of stroke or transient ischemic attack who were likely
      to be candidates for carotid angiography and endarterectomy. We used logistic
      regression to determine if the patient's race was associated with receiving
      carotid angiography and endarterectomy, after adjusting for patient's age, degree
      of eligibility for Veterans Affairs care, socioeconomic status, comorbidities
      associated with hospital admission, and geographic region of the hospital.
      RESULTS: Of the 35 922 veterans in the cohort, 3535 (9.8%) underwent angiography
      during the study period and 1249 (3.5%) had carotid endarterectomy. Blacks
      constituted 18.2% of the patients with a history of stroke or transient ischemic
      attack, 9.8% of the patients having angiography, but only 4.2% of the patients
      undergoing carotid endarterectomy. Whites constituted 77.1% of the patients with
      a history of stroke or transient ischemic attack, 86.1% of the patients receiving
      angiography, and 93.0% of those having carotid endarterectomies. After adjusting
      for confounding variables, black patients continued to have a significantly lower
      likelihood than white patients of undergoing angiography (risk ratio = 0.47; 95%
      confidence interval = 0.42, 0.53) and subsequent endarterectomy (risk ratio =
      0.28; 95% confidence interval = 0.20, 0.38). CONCLUSIONS: Socioeconomic status
      and access to care within a large managed health care system do not fully explain
      racial differences in the rate of carotid angiography and endarterectomy. Either
      referral bias for evaluation for carotid endarterectomy or racial differences in
      the extent and location of cerebrovascular disease are more important
      explanations for the observed racial variations.

PMID- 8257255
TI  - Gout and pseudogout in hospitalized patients.
AB  - BACKGROUND: We determined the clinical characteristics of acute gout and
      pseudogout in hospitalized patients and examined the morbidity of inappropriate
      treatment and misdirected investigation when the diagnosis of acute crystal
      induced synovitis was delayed. PATIENTS AND METHODS: We reviewed the medical
      records of 67 hospitalized adults seen in consultation consecutively by one
      hospital-based rheumatologist during a 64-month period between 1986 and 1991 with
      the diagnosis of acute gout or pseudogout. RESULTS: Gout was diagnosed in 41
      patients, pseudogout in 24, and both crystal-induced diseases in two. The average
      age was 75.3 years. Polyarticular disease was common in both gout (49%) and
      pseudogout (42%). Fever attributable to synovitis was present in 34% of the
      patients and was more prevalent in patients with polyarticular (50%) than
      monoarticular (20%) inflammation. A quarter of the patients encountered errors in
      diagnosis, treatment, or both before rheumatologic consultation. Eleven patients
      experienced delays in diagnosis, and six patients had the correct diagnosis but
      received ineffective treatment. CONCLUSIONS: Fever and polyarticular arthritis
      are noteworthy features in the hospitalized patient with acute gout or
      pseudogout. When the diagnosis of crystal-induced synovitis is overlooked,
      misdirected investigation and inappropriate treatment compound the morbidity of
      continued pain.

PMID- 8257256
TI  - Giant splenomegaly and refractory hypercalcemia due to extrapulmonary
      sarcoidosis. Successful treatment by splenectomy.
AB  - Sarcoidosis is a granulomatous disease of unknown origin with a variable clinical
      presentation. The presenting complaint is usually referable to the lung. We
      describe an unusual presentation of sarcoidosis in a young black man who received
      medical attention for evaluation of pancytopenia, giant splenomegaly, and marked,
      refractory hypercalcemia. After extensive evaluation, including exploratory
      laparotomy, he was found to have sarcoidosis, with extensive involvement of his
      spleen, liver, and abdominal lymph nodes. Pulmonary involvement was notably
      absent, with no suggestive findings radiographically on gallium citrate Ga 67
      scanning or on bronchoscopy with transbronchial biopsy. This patient underwent
      splenectomy and, following removal of the massive splenic granuloma burden, the
      hypercalcemia resolved completely with no other therapy.

PMID- 8257257
TI  - [Apparently supernatural healing forces from a prepared shoe].
AB  - Authors report on results of the examination of a specially prepared shoe,
      therapeutically used by a faith-healer. The patients felt unexpected sensations
      caused by an electrical circuit built in the shoe and released by the doctors big
      toe. The faith-healer justified his method to be a special kind of
      "electrophysiological therapy". The public prosecutor withdrew the impeachment on
      trickery.

PMID- 8257258
TI  - [Skull injuries caused by blow with glass bottles].
AB  - Six cases of blows with glass bottles on the skull are reported. The glass
      bottles varied in size, weight, shape and filling level. In all cases the bottles
      broke, but there were no fractures of the skull or injuries of the brain or
      meninges. As consequences of the blows with the glass bottles bruises,
      lacerations and incised wounds were seen. The only cause contributing or leading
      to death was a fatal bleeding from lacerations of the scalp.

PMID- 8257259
TI  - [Detection of skin reddening in leaving probands].
AB  - The results of 665 physical examinations of the years 1990-1992 (Department of
      Legal Medicine, Munich) were evaluated and the maximum time-interval in which
      reddenings of the skin were detectable was investigated. Reddenings without
      additional findings like pinpoint intracutaneous bleedings or superficial
      scratches could be observed up to approximately 2 days (1 day 7 hours). In cases
      with particular pin-point bleedings the changes were found up to approximately 3
      days (2 days 9 hours) after the event. The observation that reddenings with
      additional changes are longer detectable than reddenings without pin-point
      bleedings can be interpreted as an argument against a possible development of
      reddenings without additional pin-point bleedings from changes with such
      findings. This may be important for the refutation of statements concerning the
      development of such changes at a considerably earlier point of time.

PMID- 8257260
TI  - [Death sounds--a postmortem phenomenon].
AB  - "Death sounds" are monotonous sounds produced by a corpse without rigor mortis.
      Such sounds may be mistaken for signs of life, which may be of importance under
      criminal aspects. Three relevant cases are discussed.

PMID- 8257261
TI  - [Pediatric cardiology in Europe].

PMID- 8257262
TI  - [Surgical treatment of the scimitar syndrome in children, adolescents and adults.
      A cooperative study of 37 cases].
AB  - The authors report the results of a cooperative study of 37 operated cases of the
      scimitar syndrome. The diagnostic procedures, the operative indications, the
      surgical indications, the postoperative complications and the long-term outcome
      were reviewed. The results were disappointing irrespective of the surgical
      technique that was used (reimplantation of the right pulmonary veins in the left
      atrium, lobectomy, pneumonectomy). Only 12 patients had a satisfactory
      postoperative outcome and good long-term results; 21 patients had long-term
      chronic respiratory failure with a reduced exercise capacity and 4 patients died
      after surgery. Of the 21 patients with long-term sequellae, 17 had a thrombosis
      of the anastomosis between the right pulmonary veins and the left atrium; this
      occurred immediately after surgery.

PMID- 8257263
TI  - [Dilatation of critical aortic value stenosis in infants under 3 months of age.
      Our experience from 15 cases].
AB  - Between April 1988 and October 1992, 15 consecutive infants aged less than 3
      months (average 17 days) with critical valvular stenosis underwent balloon
      dilatation. Thirteen were less than 1 month old and all had low output syndromes.
      The diagnosis and follow-up assessments were made by Doppler echocardiography.
      Before valvuloplasty the maximum instantaneous gradient was 75 +/- 34 mmHg. The
      average diameter of the aortic ring was 6.8 +/- 1.3 mm. Seven patients had aortic
      rings with diameters of less than 7 mm. Ten infants had a right-to-left shunt via
      a patent ductus arteriosus and pulmonary hypertension. Dilatation was performed
      after surgical denudation of the left carotid artery: a balloon catheter with a
      diameter 0.85 times that of the aortic ring was used. After dilatation, the
      gradient was 26 +/- 18 mmHg (p < 0.001). Grade I aortic regurgitation was
      observed in 4 cases and Grade II in 2 cases. Eight patients died 1 to 100 days
      after dilatation (seven of low output and one sudden death). Of these patients, 6
      had aortic rings < 7 mm diameter. The average follow-up was 20.6 +/- 15.5 months
      (range 2 to 48 months). None of the patients had a precordial or carotid
      diastolic murmur. The gradient increased with improvement in left ventricular
      function. Two patients had a stable Grade I aortic regurgitation. Carotid Doppler
      echocardiographic control examinations performed in 4 patients were normal. Poor
      prognostic factors were: aortic ring diameter < 7 mm (p < 0.025) and a low
      gradient after dilatation (p < 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257264
TI  - [Percutaneous aortic valvuloplasty in children, non invasive evaluation and
      criteria of success].
AB  - The results of percutaneous aortic valvuloplasty in 15 children (average 8.4
      years) were evaluated by echocardiography and non-invasive criteria of the
      indication of this procedure were defined. The aortic valve was unthickened in 7
      patients (Group I) and dystrophic in the other 8 (Group II). Valvuloplasty
      decreased the transvalvular pressure gradient by 47 +/- 33%. Aortic regurgitation
      was aggravated in 4 patients. The reduction in pressure gradient was
      significantly greater in Group I than in Group II (64 +/- 19% vs 31 +/- 35%, p <
      0.05). In Group I, in contrast to Group II, the results remained stable after an
      average follow-up of 14.5 months. When the maximal instantaneous pressure
      gradient on Doppler examination was < 80 mmHg, the peak-to-peak gradient at
      catheterisation was on average 21% less, whereas when the Doppler gradient was 80
      mmHg or more, the percentage difference was only 8%. The myocardial mass index
      was over the 95th percentile in 7/8 patients with gradients > 80 mmHg whilst it
      was only increased in 1 patient with a gradient < 80 mmHg. Electrocardiographic
      LVH was observed in 6 of the 8 patients with a gradient > 80 mmHg but in none of
      the others. Although valvuloplasty reduced the transvalvular pressure gradient,
      the results were much less satisfactory in the dystrophic valves. The following
      indications were proposed for this techniques: a Doppler maximal pressure
      gradient > or = 80 mmHg, associated with at least one criterion of left
      ventricular hypertrophy.

PMID- 8257265
TI  - [Mid-term results of balloon percutaneous valvuloplasty in the treatment of
      aortic valve stenosis in children and adolescents].
AB  - Fourteen consecutive patients aged 10.2 +/- 4.2 years with congenital valvular
      aortic stenosis underwent percutaneous balloon aortic valvuloplasty (PBAV) which
      reduced the peak-to-peak LV-aortic pressure gradient from 81.2 +/- 16.7 mmHg to
      27.5 +/- 12.5 mmHg and the maximal instantaneous Doppler gradient (Dopp G) from
      70.0 +/- 13.4 mmHg to 31.4 +/- 12.3 mmHg. These 14 patients were followed up 3.6
      +/- 1.1 years after PBAV. Control Doppler examination showed the Dopp G (34.8 +/-
      15.4 mmHg) to be comparable to that measured just after PBAV (31.4 +/- 12.3
      mmHg). One patient, the only one with a mediocre, immediate result, had to be
      operated 5.5 years after PBAV. Aortic regurgitation was observed on aortography
      before PBAV in 10 patients: it remained unchanged in 7 and was aggravated in 3
      patients. Aortic regurgitation was observed for the first time after PBAV in 3
      patients. At control Doppler examination, aortic regurgitation was present on
      color Doppler in all cases but was mild or minimal in 9 cases. In one patient,
      secondary aggravation of aortic regurgitation required aortic valve replacement
      (homograft) 3 years after PBAV. Four of the 16 PBAV (25%) were performed in these
      14 patients were complicated by a femoral arterial thrombosis. This study shows
      that the good primary results of PBAV in the treatment of congenital valvular
      aortic stenosis in childhood and adolescence, are maintained at medium-term. The
      risk of creating severe aortic regurgitation is not completely negligible but
      does not seem to be out of proportion compared with surgical valvotomy.

PMID- 8257266
TI  - [Percutaneous angioplasty of aortic recoarctation: short- and mid-term results in
      18 cases].
AB  - Between January 1986 and July 1992, 18 percutaneous angioplasties were performed
      in 18 consecutive patients with recoarctation of the aorta, who were aged 2
      months to 29 years. Fifteen had been operated for coarctation of the aorta and 3
      for interruption of the aortic arch. The diameter of the dilating balloon was the
      same, to 1 mm, as that of the healthy aorta, usually measured just proximal to
      the stenosis. There were 3 femoral artery thromboses; one small aneurysm which
      did not increase in size, and 1 hypertensive crisis in a child. The diameter of
      the stenosis increased by 42.39 +/- 34.24%, the gradient decreased from 41.39 +/-
      14.58 mmHg to 23.7 +/- 16.30 mmHg and the Doppler gradient from 57.89 +/- 15.29
      mmHg to 36.55 +/- 16.50 mmHg. Eight angioplasties, including 5 of the last 7
      procedures, were considered primary successes by 2 criteria: increase of the
      diameter of the stenosis by at least 40% and a residual catheter gradient of less
      than 20 mmHg. The best results were obtained in severe, localised central
      stenoses. Sixteen patients were followed up for 2 to 69 months. Two were operated
      after failed angioplasty, without complications. No late aneurysms or restenoses
      were observed in the cases successfully dilated followed up clinically (7), by
      MRI (5) or catheterisation (2). In one case, aortography showed remodelling with
      normalisation of the aortic arch after 24 months. These results indicate that
      percutaneous angioplasty is a simple method of treating recoarctation of the
      aorta, which is most effective in severe stenoses: the immediate risk is low. The
      late risks of recoarctation and aneurysm justify systematic follow-up.

PMID- 8257267
TI  - [Perforation-dilatation of pulmonary atresia with intact interventricular septum
      in neonates and infants].
AB  - Sixteen children (14 neonates less than 1 week old and 2 infants aged 3 and 6
      months) had a "favorable" type of pulmonary atresia with an intact
      interventricular septum in which the hypoplasia of the right ventricle was mild
      and the cavity tripartite with a well developed infundibulum arriving in contact
      with a good-sized pulmonary artery from which it was separated by a totally or
      almost totally imperforate dome. They underwent a procedure associating an
      infusion of prostaglandin. E1 and an attempted pulmonary valve disobliteration by
      interventional catheterisation: needle puncture followed by balloon dilatation.
      There were 4 failed procedures (impossible puncture or dilatation), only one of
      which in the last 10 cases. The outcome of the 12 primary successes was related
      to the rapidity of recovery of right ventricular diastolic function: 7 patients
      were cured within a few days or weeks with prostaglandin therapy: 5 children
      required surgical anastomosis with a longer recovery period--3 cures but 2
      deaths. Overall, there were two myocardial effractions without serious
      complications and 1 enterocolitis which was long-lasting but eventually cured.
      Two mild residual stenoses were redilated. In conclusion, the puncture-dilatation
      technique may be used instead of surgical valvectomy in favorable forms of
      pulmonary atresia with intact septum in the neonate. With experience, it was
      possible to remove the obstruction in 9 out of 10 cases with a minimum of
      complications. It is the compulsory first stage to complete cure, the probability
      and rapidity of which depend on recovery of right ventricular compliance.

PMID- 8257268
TI  - [Atresia or congenital stenosis of the left coronary ostium. Myocardial
      revascularization in 5 children].
AB  - Five patients, 3 months to 13 year old with atresia (4) or stenosis (1) of the
      left coronary artery underwent myocardial revascularisation at Marie Lannelongue
      Hospital. The preoperative symptoms were dominated in one case by cardiac failure
      due to myocardial infarction and in the other cases by effort angina with
      syncope. The operative technique of revascularisation in one case was angioplasty
      with enlargement of the left main coronary artery with a patch and, in the
      others, bypass graft of the left coronary artery with the left internal mammary
      artery. All 5 patients survived surgery and are asymptomatic with a follow-up of
      6 months to 7 years. Control coronary angiography confirmed the patency of the
      different procedures of myocardial revascularisation. In 3 children, exercise
      electrocardiography was normal. Myocardial revascularisation of a child with a
      congenital stenotic abnormality of the left coronary network is possible, the
      technique of which depends on the diameter of the left main stenosis when the
      vessel is absent or atresic, left internal mammary artery bypass graft is the
      only solution. When the left main coronary is stenosed but patent, direct
      reconstructive surgery is an interesting alternative.

PMID- 8257269
TI  - [Comparison of long-term results of arterial switch and Senning procedure in
      transposition of great vessels with intact ventricular septum].
AB  - One hundred and five survivors after the 30th day of complete cure of
      transposition of the great arteries with intact ventricular septum between 1980
      and 1985 were followed up. Fifty-four had an arterial switch (AS) in a single
      stage at an average age of 10 +/- 9 days and 51 had Senning's procedure (S) at an
      average age of 4 +/- 2.5 months. The average follow-up (97% of patients) was 5.8
      +/- 1.1 years for the AS group and 9.3 +/- 2.3 years for the S group. The
      actuarial survival at 5 years was 100% in the AS group and 85.8% in the S group
      (p < 0.01) (8 late deaths). In the AS group, 3 patients were reoperated for
      stenosis of the pulmonary artery and, in the S group, 4 patients underwent 6
      reoperations. All but 3 patients in the S group and all but 1 patient in the AS
      group are in functional Class I of the NYHA classification. Doppler
      echocardiographic studies have shown mild to severe dysfunction of the systemic
      ventricle in 2% of the AS group and 26% of the S group (p < 0.001). Holter
      monitoring, performed in 70% of patients in the S group showed sinus node
      dysfunction in 60% and sinus rhythm in 40% of cases. In conclusion, good
      functional results were observed at over 5 years in both groups. However, the
      absence of late mortality and the minimal incidence of systemic ventricular
      dysfunction in the AS group confirm the authors' choice of indication of arterial
      switch for the treatment of transposition of the great arteries with intact
      ventricular septum.

PMID- 8257270
TI  - [Cavopulmonary shunts in the treatment of univentricular heart diseases in
      children. An experience of 60 cases].
AB  - Sixty children with a complex cardiac malformation consisting of a single
      functional ventricle and a protected pulmonary circulation, previously palliated
      by one or several Blalock anastomoses (40 cases) underwent a cavopulmonary shunt
      procedure. All but one had an excellent hemodynamic status: ventricular end
      diastolic pressure < 15 mmHg, mean pulmonary pressure < 20 mmHg, pulmonary
      vascular resistance < 3 units and a Mayo Clinic index (a combination of these
      parameters and pulmonary and systemic blood flow) < 4. The shunt was complete
      from the outset in the 27 most favorable cases which did not require any other
      surgical procedure. There were 2 immediate failures which necessitated reducing
      the reconstruction to a partial shunt; 9 cases were complicated by thrombosis of
      the intercaval connection (2 case, 1 death), by neurological complications (2
      cases, 1 death), by chronic serous effusions (5 cases): of the 21 survivors
      followed up for a maximum of 54 months (average 28 +/- 9 months), 18 were well
      and 2 handicapped by venous stasis. The shunt was partial in 33 cases, especially
      in 17 cases because it was necessary to operate the pulmonary branches, the
      subaortic area, or an atrioventricular valve; there was no immediate mortality
      but 5 complications which were related to an associated procedure in 3 cases.
      There were no complications in 28 cases: of the 30 children followed up an
      average of 24 months, there were 3 secondary degradations (2 deaths and 1 cardiac
      transplantation), 10 shunts completed 2 to 32 months later with no deaths and 8
      excellent results, and 17 children waiting for more favorable
      conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257271
TI  - [Double-chamber right ventricle, aortic subvalvular stenosis and interventricular
      septal defect. Apropos of 12 cases].
AB  - The authors report 12 cases of double-chamber right ventricle associated with
      discrete subaortic stenosis and ventricle septal defect. The statistics derived
      from 3,292 surgical reports of congenital heart diseases operated on at the Marie
      Lannelongue Surgical Center over an 8 years period show that this association is
      7 times more frequent than the law of chance. Twenty-two per cent of double
      chamber right ventricles had an associated discrete subaortic stenosis and, in 9%
      of cases of subaortic stenosis a double-chamber right ventricle was observed. The
      cause of this malformation could be a developmental defect of the primitive
      interampullar ring.

PMID- 8257272
TI  - [Mice SI/Col: a study model in the research of genes involved in situs inversus].
AB  - The SI/Col mouse is carrier of the i.v. mutation which expresses itself in an
      autosomal recessive mode. Fifty per cent of mice born of homozygotic i.v./i.v.
      parents are normal and 50% present an abnormality of lateralisation of the
      thoracic and abdominal organs with cardiac malformations involving the venous,
      atrial, ventricular and arterial segments. Identifying the i.v. mutation may
      improve our understanding of the genesis of the heterotaxic syndrome in man. With
      the help of return crossing with wild mice, the authors studied segregation of 10
      makers of the murine, chromosome 12 of the situs inversus mice. The genetic map
      constructed from this data places the i.v. mutation near the telomeric extremity
      of the murine chromosome 12. Given the inter-species conservation between this
      region and the telomeric region of the human chromosome 14, it is a candidate
      region for the search of a homologous human gene in syndromes of heterotaxis.

PMID- 8257273
TI  - [Percutaneous implantation of endoprosthesis for stenosis of branches of the
      pulmonary artery. Apropos of a case].
AB  - The authors report the case of a young man operated for tetralogy of Fallot and
      in whom surgical treatment of severe stenosis of the origins of the right and
      left pulmonary arteries had failed. Correction of these stenoses was obtained by
      implanting percutaneously an endoprosthesis in the right pulmonary artery with a
      good result: control angiography showed that the stenosis had disappeared and an
      increase in the right pulmonary artery diameter from: 5 to 11 mm, and the left
      pulmonary artery diameter from 7 to 14 mm. Perfusion pulmonary scintigraphy
      showed equal flow in the two lungs.

PMID- 8257274
TI  - [Severe hemolysis after endoluminal closure of the ductus arteriosus and recovery
      following implantation of a second obturator].
AB  - A few hours after closure of a large patent ductus arteriosus by the endoluminal
      approach in a 28 month old infant, severe hemolysis occurred due to incomplete
      closure; cure was obtained by the implantation of a second obturator by the
      femoral vein. Definitive complete occlusion of the ductus was followed by
      immediate disappearance of the hemolysis.

PMID- 8257275
TI  - [Taussig-Bing malformation with straddling of both atrioventricular valves.
      Echocardiographic description of a case].
AB  - The authors report the case of an infant with the Taussig-Bing malformation and
      straddling of the two atrioventricular valves, the diagnosis of which was made by
      echocardiography and confirmed at surgery. Anatomic repair of the transposed
      great arteries was preceded by reconstruction of the interventricular septum
      which left the abnormal tricuspid subvalvular apparatus in the right ventricle
      and the abnormal mitral subvalvular apparatus in the left ventricle.
      Postoperative Doppler echocardiography confirmed the absence of left ventricular
      outflow obstruction.

PMID- 8257276
TI  - [Familial scimitar syndrome].
AB  - The authors report a new case of a familial form of the scimitar syndrome: father
      and son. Both presented an adult form which was well tolerated. Another familial
      form has been reported in the medical literature: father and daughter. The
      authors discuss the possible genetic mode of transmission in the light of these
      two cases.

PMID- 8257277
TI  - [Aptitude for sports in case of congenital heart block. Apropos of a case].
AB  - Cardiorespiratory adaptation of congenital atrioventricular block is not well
      known. The authors present the case of a 20 year old patient with excellent
      muscular force and maximal aerobic capacity despite severe chronotropic
      insufficiency on exercise, the heart rate not exceeding 80/mn. This condition may
      be explained by increased peripheral oxygen uptake and an increased oxygen
      transport due to high hemoglobin level.

PMID- 8257278
TI  - [Exertion syncope disclosing supravalvular mitral stenosis in an infant].
AB  - An infant with frequent upper airways infections presented syncopes during meals
      and weeping since the age of eleven months. Cardiac examination was always
      normal. At 14 months of age, an echocardiogram with colour Doppler demonstrated a
      severely stenotic isolated supramitral membrane with severe pulmonary
      hypertension. The membrane was immediately excised curing the malformation and
      suppressing definitively the syncopes, probably due to decreased cerebral blood
      flow during exertion. An echocardiogram should always be performed when syncopes
      remain unexplained in small children. It allows early diagnosis and treatment of
      congenital heart defects which do not have auscultatory findings especially those
      resulting in severe pulmonary venous obstruction.

PMID- 8257279
TI  - Zymobacter palmae gen. nov., sp. nov., a new ethanol-fermenting peritrichous
      bacterium isolated from palm sap.
AB  - Zymobacter palmae gen. nov., sp. nov. was proposed for a new ethanol-fermenting
      bacterium that was isolated from palm sap in Okinawa Prefecture, Japan. The
      bacterium is gram-negative, facultatively anaerobic, catalase-positive, oxidase
      negative, nonsporeforming and peritrichously flagellated. It requires nicotinic
      acid for growth. It ferments hexoses, alpha-linked di- and tri-saccharides, and
      sugar alcohols (fructose, galactose, glucose, mannose, maltose, melibiose,
      saccharose, raffinose, mannitol and sorbitol). Fifteen percent of maltose in
      broth medium is effectively fermented, whereas glucose with a concentration
      higher than 10% delayed growth initiation and decreased growth rates. Maltose is
      fermented to produce ethanol and CO2 with a trace amount of acids. Approximately
      2 mol of ethanol are produced from 1 mol moiety of hexose of maltose. The
      organism possesses ubiquinone-9. The G + C content of the DNA is 55.8 +/- 0.4
      mol%. Major cellular fatty acids were palmitic and oleic acids and cyclopropanic
      acid of C19:0. Characteristic hydroxylated acid was 3-hydroxy dodecanoic acid.
      The bacterium is distinct from other ethanol-fermenting bacteria belonging to the
      genera Zymomonas Kluyver and van Niel 1936 and Saccharobacter Yaping et al. 1990
      with respect to chemotaxonomic and other phenotypic characters to warrant to
      compose a new genus and a new species. The type strain is strain T109 (= IAM
      14233).

PMID- 8257280
TI  - Biosynthesis and cytoplasmic accumulation of a chlorinated catechol pigment
      during 3-chlorobenzoate aerobic co-metabolism in Pseudomonas fluorescens.
AB  - A strain of Pseudomonas fluorescens was capable of co-metabolizing 3
      chlorobenzoic acid with the production of a chlorinated catechol black pigment. A
      peroxidase and another enzymatic activity referred to as a polyphenol oxidase
      were found to be involved in the oxidation of 4-chlorocatechol to 4-chloro-1,2
      benzoquinone, i.e. in the production of highly reactive substrates for pigment
      formation. Therefore, P. fluorescens cells were seen to take an active part not
      only in 3-chlorobenzoate mineralization but also in overall pigment production.
      pH was found to be a key parameter in the regulation of the activity of P.
      fluorescens oxidoreductive enzymes. Ultrastructural investigations showed that
      electron dense granules of pigment were distributed throughout the cytoplasm of
      Pseudomonas fluorescens cells grown in presence of 3-chlorobenzoate, as confirmed
      also by Thiery cytochemical investigations. In these cells, an extensive
      contraction of the cytoplasm as well as a significant damage to the cell wall
      after two days of incubation, suggested that pigment production caused a
      premature death of the cells accompanied by the leakage of the cell content.
      Pigment production seemed to occur mostly in the cytoplasmic context where the
      electron dense material accumulates until it is released in the medium after the
      cell lysis.

PMID- 8257281
TI  - Is intracytoplasmic membrane structure a generic criterion? It does not coincide
      with phylogenetic interrelationships among phototrophic purple nonsulfur
      bacteria.
AB  - The 16S rRNA or rRNA gene sequences of the type strains of 5 species of
      Rhodobacter, Rhodopseudomonas blastica and Paracoccus denitrificans were
      determined. The sequence analysis revealed that Rhodobacter species, whose
      intracytoplasmic membrane systems were characteristically vesicular, composed a
      sole cluster. Rhodopseudomonas blastica, whose intracytoplasmic membrane system
      was lamellar, was included in the cluster of Rhodobacter. The phylogenetic co
      clustering of these bacteria conformed to their possessing of the identical types
      of carotenoids. Paracoccus denitrificans, which is nonphototrophic, is a right
      member of the Rhodobacter cluster. Rhodobacter species, Rhodopseudomonas blastica
      and Paracoccus denitrificans are apart from the other phototrophic bacteria and
      have the common deletions of 21 bases at the positions 1258 to 1278 (Escherichia
      coli numbering system). It was demonstrated that the morphological character
      "intracytoplasmic membrane structure", that has been regarded as a generic
      criterion does not reflect the phylogeny in the phototrophic bacteria. The
      transfer of Rhodopseudomonas blastica to the genus Rhodobacter is proposed.

PMID- 8257282
TI  - Characterization of hydrogenosomes and their role in glucose metabolism of
      Neocallimastix sp. L2.
AB  - In the anaerobic fungus Neocallimastix sp. L2 fermentation of glucose proceeds
      via the Embden-Meyerhof-Parnas pathway. Enzyme activities leading to the
      formation of succinate, lactate, ethanol, and formate are associated with the
      cytoplasmic fraction. The enzymes 'malic enzyme,' NAD(P)H:ferredoxin
      oxidoreductase, pyruvate:ferredoxin oxidoreductase, hydrogenase,
      acetate:succinate CoA transferase and succinate thiokinase leading to the
      formation of H2,CO2, acetate, and ATP are localized in microbodies. Thus, these
      organelles are identified as hydrogenosomes. In addition, the microbodies contain
      the O2-scavenging enzymes NADH- and NADPH oxidase, while NAD(P)H peroxidase,
      catalase, or superoxide dismutase could not be detected. In cell-free extracts
      from zoospores of Neocallimastix sp. L2 the specific activities of hydrogenosomal
      enzymes as well as the quantities of these proteins are 2- to 6-fold higher than
      in mycelium extracts. These findings suggest that hydrogenosomes perform an
      important role--especially in zoospores--as H2-evolving, ATP-generating and O2
      scavenging organelles.

PMID- 8257283
TI  - Characterization of acetyl-CoA: L-lysine N6-acetyltransferase, which catalyses
      the first step of carbon catabolism from lysine in Saccharomyces cerevisiae.
AB  - The carbon catabolism of L-lysine starts in Saccharomyces cerevisiae with
      acetylation by an acetyl-CoA:L-lysine N6-acetyltransferase. The enzyme is
      strongly induced in cells grown on L-lysine as sole carbon source and has been
      purified about 530-fold. Its activity was specific for acetyl-CoA and, in
      addition to L-lysine, 5-hydroxylysine and thialysine act as acetyl acceptor. The
      following apparent Michaelis constants were determined: acetyl-CoA 0.8 mM, L
      lysine 5.8 mM, DL-5-hydroxylysine, 2.8 mM, L-thialysine 100 mM. The enzyme had a
      maximum activity at pH 8.5 and 37 degrees C. Its molecular mass, estimated by
      sodium dodecyl sulphate-polyacrylamide gel electrophoresis, was 52 kDa. Since the
      native molecular mass, determined by gel filtration, was 48 kDa, the enzyme is a
      monomer.

PMID- 8257284
TI  - Delivery of primary care to the physically challenged.
AB  - The specialty of physical medicine and rehabilitation evolved beyond conventional
      medical views to include consideration of the needs of the physically disabled
      person's function and quality of life. A care delivery system of medical
      rehabilitation programs and services then evolved. Recently, the United States'
      health care system has been recognized as being deficient in meeting the on-going
      health care needs of the physically disabled after they have completed medical
      rehabilitation needs. We discuss the history of the health care needs of the
      physically challenged and we examine current issues of need and delivery of
      services. We also describe an innovative model program designed to meet those
      needs.

PMID- 8257285
TI  - Post-rehabilitation health care for people with disabilities: an update on the
      1989 White Paper of the American Congress of Rehabilitation Medicine.

PMID- 8257286
TI  - Addressing the post-rehabilitation health care needs of persons with
      disabilities. The ACRM Committee on Social, Ethical, and Environmental Aspects of
      Rehabilitation. American Congress of Rehabilitation Medicine.

PMID- 8257287
TI  - Cell-to-cell movement of plant viruses. Insights from amino acid sequence
      comparisons of movement proteins and from analogies with cellular transport
      systems.
AB  - Cell-to-cell movement is a crucial step in plant virus infection. In many
      viruses, the movement function is secured by specific virus-encoded proteins.
      Amino acid sequence comparisons of these proteins revealed a vast superfamily
      containing a conserved sequence motif that may comprise a hydrophobic interaction
      domain. This superfamily combines proteins of viruses belonging to all principal
      groups of positive-strand RNA viruses, as well as single-stranded DNA containing
      geminiviruses, double-stranded DNA-containing pararetroviruses (caulimoviruses
      and badnaviruses), and tospoviruses that have negative-strand RNA genomes with
      two ambisense segments. In several groups of positive-strand RNA viruses, the
      movement function is provided by the proteins encoded by the so-called triple
      gene block including two putative small membrane-associated proteins and a
      putative RNA helicase. A distinct type of movement proteins with very high
      content of proline is found in tymoviruses. It is concluded that classification
      of movement proteins based on comparison of their amino acid sequences does not
      correlate with the type of genome nucleic acid or with grouping of viruses based
      on phylogenetic analysis of replicative proteins or with the virus host range.
      Recombination between unrelated or distantly related viruses could have played a
      major role in the evolution of the movement function. Limited sequence
      similarities were observed between i) movement proteins of dianthoviruses and the
      MIP family of cellular integral membrane proteins, and ii) between movement
      proteins of bromoviruses and cucumoviruses and M1 protein of influenza viruses
      which is involved in nuclear export of viral ribonucleoproteins. It is
      hypothesized that all movement proteins of plant viruses may mediate hydrophobic
      interactions between viral and cellular macromolecules.

PMID- 8257289
TI  - Determination of human rotavirus VP4 using serotype-specific cDNA probes.
AB  - The VP4 genetic groups of 151 field strains of human rotaviruses obtained from
      infants and young children with diarrhea from four locations in Malaysia were
      analyzed. The strains were adapted to growth in tissue culture and studied
      further by molecular hybridization of northern blotted RNA to PCR-generated cDNA
      probes representing amino acids 84-180 of the KU strain VP4, 83-181 of the DS-1
      strain VP4, and 83-180 of either the 1076 or K8 strain VP4, representing VP4
      genetic groups 1-4 (P1A, P1B, P2, and P3), respectively. The majority (79% of the
      field strains hybridized with the KU VP4 genetic group 1 probe and were
      associated with G1, G3, G4, untypable, or mixed G serotypes. VP4 genetic group 1
      (P1A) strains were the most common in all locations in Malaysia between 1978
      1988. Three strains which exhibited G3 and subgroup I specificity hybridized with
      the K8 VP4 genetic group 4 probe. These three VP4 genetic group 4 (P3) strains
      were detected in two different years and locations, extending the initial
      detection of this VP4 genetic group (the K8 strain) in Japan to a larger
      geographical area of Asia.

PMID- 8257288
TI  - The pathogenicity of a US3 protein kinase-deficient mutant of herpes simplex
      virus type 2 in mice.
AB  - We have investigated the pathogenicity of a US3 protein kinase-deficient mutant
      (L1 BR1) of herpes simplex virus type 2 (HSV-2) for 4-week-old ICR mice to define
      the role of the viral protein kinase in virus-host interaction. When mice were
      intraperitoneally infected with 10(5)PFU of L1 BR1, the virus disappeared from
      the peritoneal cavity by 2 days postinfection and failed to induce any
      significant histopathological changes in the liver and spleen although viral
      antigens were occasionally detected in the epithelial cells of small bile ducts
      and small vascular wall. The parental virus (HSV-2 186) and a revertant of the
      mutant (L1 B-11) both caused severe hepatitis, and viral antigens were clearly
      detected in the hepatocytes and Kupffer cells in the focal necrotic areas. Both
      of the virulent viruses, unlike L1 BR1, could produce infectious progeny and
      cytopathic effects in freshly harvested peritoneal macrophages. The growth of L1
      BR1 in peritoneal macrophages was restricted at a stage of or prior to viral DNA
      synthesis but after the induction of viral DNA polymerase. In addition, the
      production and/or the spread of mutant in mouse embryo fibroblasts (MEF) was
      found to be much more effectively suppressed by cocultivation of peritoneal
      macrophages than that of 186. An almost complete inhibition of L1 BR1-plaque
      formation was observed at a macrophage-to-MEF ratio of 4:1. These results suggest
      that the attenuation of L1 BR1 following intraperitoneal infection is primarily
      due to its high sensitivity to intrinsic and extrinsic inhibition of peritoneal
      macrophages and that the US3 protein kinase may play a role in viral DNA
      replication in peritoneal macrophages.

PMID- 8257290
TI  - Regulatory effects of matrix protein variations on influenza virus growth.
AB  - Influenza virus A/WSN/33 forms large plaques (> 3 mm diameter) on MDCK cells
      whereas A/Aichi/2/68 forms only small plaques (< 1 mm diameter). Fast growing
      reassortants (AWM), isolated by mixed infection of MDCK cells with these two
      virus strains in the presence of anti-WSN antibodies, all carried the M gene from
      WSN. On MDCK cells, these reassortants produced progeny viruses as rapidly as did
      WSN, and the virus yield was as high as Aichi. The fast-growing reassortants
      overcame the growth inhibitory effect of lignins. Pulse-labeling experiments at
      various times after virus infection showed that the reassortant AWM started to
      synthesize viral proteins earlier than Aichi. Taken together, we conclude that
      upon infecting MDCK cells, the reassortant viruses advance rapidly into the
      growth cycle, thereby leading to an elevated level of progeny viruses in the
      early period of infection. Possible mechanisms of the M gene involvement in the
      determination of virus growth rate are discussed, in connection with multiple
      functions of the M proteins.

PMID- 8257291
TI  - Interleukin-1 production and cell-activation response to cytomegalovirus
      infection of vascular endothelial cells.
AB  - Human cytomegalovirus (HCMV) is a source of major complications in
      immunosuppressed individuals, and endothelial involvement in HCMV infection is
      well documented. Traditionally laboratory strains of HCMV have been used in
      experimental investigations in vitro; however the continuous propagation of these
      strains in fibroblasts have attenuated the virus making it unsuitable for
      infecting other cell systems such as endothelial cells. In this study a recent
      clinical isolate of HCMV was propagated through several passages in endothelial
      cells and was used to investigate the effect of HCMV infection of human umbilical
      vein endothelial cells (HUVEC) on IL-1 production and cell proliferation.
      Infection of HUVEC with the clinical isolate of HCMV (at multiplicity of
      infection 5:1) suppressed the production of IL-1 alpha (82%) and IL-1 beta (99%)
      at 5 h post infection; the levels returned to that of the control within 24h post
      infection. Ultraviolet inactivated (but not heat killed) virus produced similar
      suppression confirming that a thermolabile viral structural protein or intact
      virion were responsible for this suppression. Infection of HUVEC with the
      clinical isolate increased the number of these cells and the rate of their
      proliferation. An increase of infected HUVEC number under quiescent growth
      conditions continued as the infection progressed (6-10 days post infection),
      exhibiting, at 3 days post infection, 5 times the number of uninfected HUVEC
      (control) which did not tolerate the quiescent culture conditions for more than 4
      days. Live virus is responsible for this increase because UV-inactivated virus
      did not maintain the proliferation of HUVEC. These studies suggest that while
      infection of HUVEC with a recent clinical isolate of HCMV suppressed the
      production of IL-1 at early hours after infection, it increased the proliferation
      of these cells at later stages of infection.

PMID- 8257292
TI  - Dynamics of bovine respiratory syncytial virus infections: a longitudinal
      epidemiological study in dairy herds.
AB  - To study the epidemiology of respiratory syncytial virus (RSV) infections during
      the year, the incidences of primary infections and reinfections were monitored by
      titrating antibodies to bovine RSV (BRSV) in cattle above 2 months of age in 6
      dairy herds in the Netherlands. From August 1990 until September 1991, 884 cattle
      were sampled at one-month intervals. A total of 155 cattle, most under two years
      of age, had a primary antibody response. Antibody rises were found in 259 cattle
      of all ages. The highest incidences of BRSV infections were found in one period
      either in autumn or winter. In other seasons, primary infections were rare,
      whereas reinfections were not uncommon. In 5 out of the 6 herds, two seronegative
      sentinel calves were introduced at the end of the winter and none developed
      specific antibodies before the next winter. The observations strongly suggest
      that, in spite of regular reinfections, BRSV circulates during spring or summer
      at a very low level or not at all. Persistent BRSV infection in a number of cows
      might be a means for the virus to survive during summer, but a steady rate of
      reinfection of seropositive cows throughout the year at a low level might also
      maintain a reservoir of infectious virus. This study adds to the knowledge of
      frequency and timings of primary infections and reinfections of BRSV and it might
      contribute to the study of these issues of human RSV.

PMID- 8257293
TI  - Structure, function, and intracellular localization of glycoprotein B of
      herpesvirus simian agent 8 expressed in insect and mammalian cells.
AB  - The cloned gene of glycoprotein B (gB) of herpesvirus simian agent 8 (SA 8) was
      expressed with a baculovirus system in insect cells. Expression of gB was easily
      detectable over the cellular background by Coomassie staining of
      electrophoretically separated proteins. Endoglycosidase digestion of
      immunoprecipitated gB revealed that the gene product is N-glycosylated, but only
      with unprocessed, endoglycosidase-H sensitive carbohydrates. The lack of terminal
      glycosylation of gB is consistent with the observation that gB expressed in
      insect cells has a molecular weight slightly lower than gB synthesized during an
      SA 8 infection in mammalian cells. The truncated carbohydrates of gB from insect
      cells have no measurable effect on the tertiary structure of gB.
      Immunofluorescence studies on mammalian cells expressing gB from a simian virus
      40 based vector revealed that the glycoprotein is localized to cytoplasmic
      membranes, to the plasma membrane and to the nuclear envelope. Cells expressing
      gB were fused to polykaryons, which shows that gB has cell fusing activity in the
      absence of any other SA 8 gene product.

PMID- 8257294
TI  - Two proteinase activities in HCV polypeptide expressed in insect cells using
      baculovirus vector.
AB  - Processing of HCV viral precursor protein requires at least two viral
      proteinases, Cpro-1 and Cpro-2, in addition to cellular proteinases. The HCV
      polypeptide that covers the region for the two viral proteinase domains was
      expressed in insect cells using a baculovirus expression system. The two
      proteinase activities were demonstrated in the infected cells. The Cpro-1
      dependent cleavage site was estimated from the amino acid sequence of the N
      terminus of the processed product. Analyses of the susceptibilities of various
      mutants altered at position P1 and P1' of the putative cleavage site suggested
      that amino acid residues at these positions is not essential for recognition and
      cleavage by Cpro-1-dependent activity.

PMID- 8257295
TI  - Sequence analysis of hepatitis B virus DNA in immunologically negative infection.
AB  - It was previously demonstrated that the serum of some patients without
      immunological evidence of HBV infection contains the virus. Here we demonstrated
      by sequence analysis that the serum of such a patient contained a mixed HBV
      population. In comparison with HBV genomes of different genotypes twenty-two
      nucleotide variations were found in all clones sequenced in parallel. One
      nucleotide variation was identified within the enhancer I. Twelve of the twenty
      two nucleotide variations caused altogether fifteen changes of amino acid
      sequence in known or predicted viral proteins. The proteins of the P open reading
      frame, which are most important for viral replication, were affected by nine
      amino acid substitutions. Three amino acid substitutions concerned the product of
      the X gene, a transcriptional transactivator of various viral and cellular
      promoters. Three mutations were only observed in some of the clones. One point
      mutation affected the direct repeats of the enhancer II. It occurred together
      with an 8 bp-deletion involving the C promoter region and the X gene. The third
      mutation was a single insertion, causing a fusion of the X and C gene. One or
      several of the identified mutations could be responsible for the diminished rate
      of replication and consequently for the low-titred, immunologically negative HBV
      infection.

PMID- 8257296
TI  - Characterization of two divergent adenovirus 31 strains.
AB  - Two divergent strains of adenovirus type 31 were analyzed by neutralization test
      and restriction endonuclease (RE) patterns in an effort to find the basis for
      their genetic variability. One strain, isolated from the throat of a child in
      Maryland during an upper respiratory illness in 1968, was partially neutralized
      by Ad 31 antisera (to 16-fold lower than homologous titer) while its own
      antiserum fully neutralized prototype Ad 31 virus, but shared only 9% of
      comigrating RE fragments with Ad 31 prototype (vs. 30% with Ad 18 prototype);
      however, PCR tests specific for the inverted terminal repeat (ITR) sequence of
      Ads 12 and 18 were negative. The other strain, recovered from a stool sample from
      an infant with diarrhea in Georgia in 1979, was inhibited by Ad 31 antiserum to
      within 4-fold homologous titer, but shared only 15% of comigrating fragments with
      Ad 31 prototype (vs. 91% with Ad 18 prototype); ITR-specific PCR tests with this
      virus were positive for Ad 12/Ad 18. These data suggest that both strains are
      from separate evolutionary lines of Ad 31 unrelated to all other isolates studied
      to date by RE analysis, and that the partial neutralization by prototype Ad 31
      antisera might represent small mutations in the hexon gene.

PMID- 8257297
TI  - Ebola protein analyses for the determination of genetic organization.
AB  - Amino-acid sequencing of the purified major nucleoprotein (NP), VP35 and VP40
      from purified Ebola virus proved that they are the protein products of the first
      three genes, and that the open reading frame (ORF) of the NP begins at nucleotide
      470. Because of the many unusual features of the ORFs of Ebola virus, we thought
      that our conclusions should be substantiated. Comparisons of in vitro-translation
      products to purified viral proteins were used to demonstrate conclusively that
      the NP, VP35 and VP40 were the protein products of genes one, two, and three,
      respectively. Studies using antibodies to synthetic peptides matching the N- and
      C-termini of the deduced sequences from these genes confirmed these conclusions
      and that the ORF for the NP begins at nucleotide 470. Subsequent studies
      confirmed that VP30 is encoded by the fifth gene.

PMID- 8257298
TI  - Influenza A virus reassortants with surface glycoprotein genes of the avian
      parent viruses: effects of HA and NA gene combinations on virus aggregation.
AB  - A series of 33 human-avian and human-mammalian influenza virus reassortant clones
      possessing either HA or both HA and NA genes of the avian or mammalian virus was
      obtained by crosses of A/USSR/90/77 (H1N1) human virus with 5 avian and 1
      mammalian influenza virus strains. All of the reassortants possessing NA genes of
      the H1N1 human parent virus and HA gene of an avian or mammalian parent virus had
      high values of infectivity/HA activity ratio. Since this feature could result
      from a limited virion aggregation, several reassortants were analyzed by velocity
      sucrose gradient centrifugation. In all cases tested, the reassortants of H3N1,
      H4N1, H10N1 and H13N1 composition were shown to be aggregated, whereas the
      preparations of the parent H1N1 virus and the reassortants possessing both HA and
      NA genes from the avian parents were represented mostly by single virions. The
      aggregates were formed at 4 degrees C and dissociated at 37 degrees C. The
      dissociation was blocked by an inhibitor of neuraminidase activity (2-deoxy-2,3
      dehydro-N-acetyl-neuraminic acid). The dissociation was reversible since the
      virions reaggregated at 4 degrees C; however, treatment with bacterial
      neuraminidase led to an irreversible dissociation of the aggregates. The tendency
      of the reassortants to aggregate correlates with an increased infectivity/HA
      ratio. No regular decrease in the neuraminidase activity in the virions of
      reassortants as compared to the parent H1N1 virus was revealed. The most likely
      explanation of the observed phenomenon seems to be an inefficient removal of
      sialic acid residues from the avian virus hemagglutinin by the human virus N1
      neuraminidase.

PMID- 8257299
TI  - In vitro reconstitution of rotavirus transcriptional activity using viral cores
      and recombinant baculovirus expressed VP6.
AB  - Purified baculovirus-expressed group A rotavirus VP6 polypeptide was shown to be
      active in the recovery of the transcriptase activity associated with the
      reconstitution of the single-shelled rotavirus particle. Recombinant VP6
      polypeptide was able to restore the transcriptional activity in purified viral
      cores from both SA-11 and RF rotavirus strains. Recombinant group C VP 6 (Cowden
      strain) is capable of binding as a trimer to group A viral core particles but
      unable to restore the transcriptase activity, suggesting that the binding of the
      polypeptide to cores is not the only requirement to restore the transcriptase
      activity. The VP 6 group A polypeptide was shown to bind as a monomer to viral
      cores, indicating that trimerization of VP 6 may be not required for
      reconstitution of the polymerase activity.

PMID- 8257300
TI  - Tumour induction by transplacental infection with polyoma virus of the F1
      generation of Wistar rats.
AB  - Intravenous polyoma virus inoculation into pregnant Wistar rats resulted in
      transplacental infection of the foetus, causing tumours and hydronephroses.
      Cyclosporin A reduced these effects significantly.

PMID- 8257301
TI  - Consumption coagulopathy associated with shock in acute African swine fever.
AB  - We studied the evolution of shock using a comprehensive array of haematological
      tests in pigs infected with the highly virulent strain Malawi '83 (Lilongwe
      20/1). A sudden onset of illness was observed between day 5 and 7 after
      inoculation with development of flush, episodes of epistaxis and melaena. Prior
      to these clinical signs, initiation of a consumption coagulopathy was
      demonstrated with loss of antithrombin III and plasminogen activity. Our findings
      indicate that during infection with this highly virulent strain the development
      of a consumption coagulopathy precedes and possibly contributes to shock, which
      results in haemorrhage and death.

PMID- 8257302
TI  - Enhanced replication of porcine reproductive and respiratory syndrome (PRRS)
      virus in a homogeneous subpopulation of MA-104 cell line.
AB  - Two different cell populations, high- (MARC-145) and low-permissive cell clones
      (L-1) to porcine reproductive and respiratory syndrome (PRRS) virus, were derived
      from MA-104 cell line (parent cell: P) by cell cloning. Maximum virus yields in
      MARC-145, P, and L-1 cell clones were 10(8.5), 10(3.5), and 10(2.5) tissue
      culture infective dose 50 (TCID50)/0.1 ml, respectively. The MARC-145 cell clone
      supported replication of all 11 different porcine reproductive and respiratory
      syndrome virus isolates that were tested. These results indicated that the MARC
      145 cells will be useful for PRRS virus replication.

PMID- 8257303
TI  - Three new cases of R-type virus-like particles in hamster tumours.
AB  - R-type virus-like particles (VLP) in fibrosarcoma and myeloid tumour induced in
      hamsters with the myeloleukaemic virus of Graffi and in hamster embryonic
      fibroblasts infected with the lympholeukaemic virus Ly/Ya are described. The
      particles are found in the cysternae of the rough surface endoplasmic reticulum
      (RER). The VLP are classified as endogenous virus (EV) whose expression is
      determined by the initial infection with murine leukaemia virus (MLV).

PMID- 8257304
TI  - On stuttering and global ischemia.

PMID- 8257305
TI  - An aggressive approach to massive middle cerebral artery infarction.
AB  - OBJECTIVE: We report favorable outcome after surgical decompression, or
      strokectomy, guided by xenon-enhanced computed tomographic studies of cerebral
      blood flow in the setting of potentially fatal swelling from massive cerebral
      infarction. DESIGN: Retrospective analysis with 3 months to 3 years of follow-up.
      SETTING: University of Pittsburgh (Pa) Medical Center, a tertiary care university
      referral center. PATIENTS: Four patients, aged 14 to 46 years, presented with
      focal neurologic deficits appropriate for a massive middle cerebral artery
      infarction (two dominant and two nondominant). In spite of medical therapy, all
      patients deteriorated to at least a decreased level of consciousness.
      INTERVENTION: Using xenon-enhanced computed tomographic studies of cerebral blood
      flow in three patients, areas of severely ischemic (blood flow, < 5 mL/100 g per
      minute), nonviable brain were identified and resected. OUTCOME MEASURE: Outcome
      was measured by survival and ability to perform activities of daily living.
      RESULTS: Postoperatively, all patients recovered rapidly (< 6 hours) to the level
      of function at admission and were able to perform the activities of daily living
      with minimal or no assistance. CONCLUSION: Despite deficits appropriate to the
      area of infarction, prompt management of life-threatening postinfarction swelling
      by surgical decompression can yield favorable outcome.

PMID- 8257306
TI  - Anti-peripheral nerve myelin antibodies and terminal activation products of
      complement in serum of patients with acute brachial plexus neuropathy.
AB  - OBJECTIVE: To determine if complement-fixing antibodies to peripheral nerve
      myelin (anti-PNM antibodies) and terminal complement activation products were
      increased in serum of patients with brachial plexus neuropathy compared with
      normal controls. DESIGN: Case series. SETTING: University medical center.
      PATIENTS: Three patients (aged 6, 39, and 51 years) with acute brachial plexus
      neuropathy were studied during the acute and recovery phase of their disease.
      METHODS: Anti-PNM antibodies were measured in serum samples obtained from three
      patients and 25 normal controls with the C1 fixation and transfer assay. Soluble
      terminal complement activation products, SC5b-9, were measured by enzyme-linked
      immunosorbent assay (ELISA) in serum samples of one patient with brachial plexus
      neuropathy and of five normal controls. RESULTS: Both serum anti-PNM antibodies
      and soluble terminal complement activation products were increased in the acute
      phase of brachial plexus neuropathy compared with normal control values and
      decreased several months later during clinical recovery. CONCLUSION: Complement
      dependent, antibody-mediated demyelination may participate in the peripheral
      nerve damage of brachial plexus neuropathy.

PMID- 8257307
TI  - Locomotion of autistic adults.
AB  - OBJECTIVE: To assess gait in patients with autism. DESIGN: Clinical and
      physiologic assessment. SETTING: Research hospital. PATIENTS AND SUBJECTS: Five
      adults with autism and five healthy, age-matched control subjects. MAIN OUTCOME
      MEASURE(S): Clinical and biomechanical assessment. RESULTS: Clinical assessment
      showed mild clumsiness in four patients and upper limb posturing during gait in
      three patients. The velocity of gait, step length, cadence, step width, stance
      time, and vertical ground reaction forces were normal in all patients. The only
      significant abnormality was decreased range of motion of the ankle. Some patients
      exhibited slightly decreased knee flexion in early stance. Clinically, the gait
      appeared to be irregular in three patients, but the variability was not
      significantly increased. CONCLUSIONS: The findings in patients with autism
      indicate a nonspecific, neurological disturbance involving the motor system. The
      normal velocity of gait and the normal step length argue against a parkinsonian
      type disturbance, whereas the clinical picture suggests a disturbance of the
      cerebellum.

PMID- 8257308
TI  - End-stage Alzheimer's disease. Glasgow Coma Scale and the neurologic examination.
AB  - OBJECTIVE: To characterize the cognitive and neurologic features of patients with
      end-stage Alzheimer's disease using a standard neurologic examination and the
      Glasgow Coma Scale. DESIGN: Case series. SETTING: Local community nursing homes.
      PATIENTS: Forty patients with Alzheimer's disease were drawn from previously
      enrolled subjects in the Rochester Alzheimer's Disease Project with Clinical
      Dementia Rating scores of 3, 4, or 5. MAIN OUTCOME MEASURES: Scores on the
      Glasgow Coma Scale and cognitive screening examinations and the prevalence of
      neurologic manifestations such as primitive reflexes and extrapyramidal signs
      were compared across the Clinical Dementia Rating groups. RESULTS: When compared
      with patients in the Clinical Dementia Rating stages 3 and 4, patients with a
      stage 5 scored significantly lower on the Glasgow Coma Scale, with the
      discriminating subscales being verbal and motor responses. Primitive reflexes,
      myoclonus, and dyskinesia were increasingly prevalent in the more terminal
      stages. Cognitive screening assessments did not discriminate between groups.
      CONCLUSIONS: Rudimentary neurologic functions can be readily assessed and, when
      viewed together with the Glasgow Coma Scale, may circumvent the "floor effect"
      frequently encountered when using the currently available cognitive and
      functional scales and, thereby, better define patients with end-stage Alzheimer's
      disease.

PMID- 8257309
TI  - Human immunodeficiency virus-associated motor axonal polyradiculoneuropathy.
AB  - OBJECTIVE: To report two cases of an axonal motor polyradiculoneuropathy
      associated with human immunodeficiency virus infection in otherwise asymptomatic
      subjects. DESIGN: Case series. SETTING: Tertiary care hospital neurology
      inpatient service. RESULTS: Electrophysiologic testing showed acute denervation
      with almost normal sensory potentials and no evidence of demyelination.
      CONCLUSIONS: These cases present an example of an acute axonal
      polyradiculoneuropathy in persons infected with human immunodeficiency virus
      without acquired immunodeficiency syndrome.

PMID- 8257310
TI  - Trimethyltin encephalopathy.
AB  - A chemistry student was acutely exposed to vapors of an organotin compound.
      Seventy-two hours later, he exhibited delirium, spatial disorientation,
      perseveration, inappropriate affect, and memory defects. Five months later, he
      experienced episodes of complex partial seizures, which continue to require
      anticonvulsant medication after 7 years. Trimethyltin was identified in blood and
      urine samples taken 17 days after the accident; the blood level of trimethyltin
      was elevated 35 days after exposure. Serial electroencephalograms showed
      persistent left temporal paroxysmal epileptogenic potentials. Serial
      neuropsychological tests revealed persistent memory defects, cognitive
      dysfunction, and dysphoria 4 years after exposure. We review acute, resolving,
      and long-term residual neurotoxic effects of trimethyltin in man. We describe
      detailed clinical observations, serial neuropsychological test results,
      electroencephalographic findings, and exposure data in this patient, confirming
      the limbic system effects of trimethyltin and relating them to the known
      histopathologic pattern of this condition.

PMID- 8257311
TI  - Lower motor neuron dysfunction associated with human immunodeficiency virus
      infection.
AB  - OBJECTIVE: The association of human immunodeficiency virus with a clinical
      picture of motor neuron disease is uncommon, with three cases reported to date.
      This case represents an additional case of a human immunodeficiency virus
      infected patient with apparent motor neuron disease. DESIGN: Single patient case
      report. SETTING: Large urban public hospital. PATIENT: A 45-year-old human
      immunodeficiency virus-positive Hispanic man who presented with muscle wasting,
      fasciculations, areflexia, cranial nerve deficits, and weakness progressing to a
      complete quadriplegia. RESULTS: Electrophysiologic data showed evidence of
      diffuse denervation with normal sensory and motor nerve conductions and no
      evidence of demyelination. Electromyography showed diffuse sharp waves and
      fibrillation. CONCLUSIONS: This case demonstrates a progressive motor neuron
      dysfunction in a patient positive for the human immunodeficiency virus and
      provides additional evidence that infection with the human immunodeficiency virus
      should be considered in the differential diagnosis of apparent motor neuron
      disease.

PMID- 8257312
TI  - Echocardiographic values in the greyhound.
AB  - Serial B- and M-mode echocardiography was performed on Greyhounds to determine
      normal cardiac values for this breed. These were generally of greater magnitude
      than predicted from previous echocardiographic research on other breeds and cross
      breeds. In particular, left ventricular posterior wall thickness, measured at
      both systole and diastole, was consistently greater.

PMID- 8257313
TI  - Factors affecting the prevalence and severity of footrot in a merino flock
      selected for resistance to Haemonchus contortus.
AB  - An outbreak of virulent footrot occurred in three lines of sheep selected for
      different levels of resistance to Haemonchus contortus, providing an opportunity
      to examine the factors affecting footrot severity. The selection lines did not
      differ significantly in average footrot score, but various other factors were
      found to have an effect. In breeding ewes, the average score was 10.2 (maximum
      possible score 20) and the prevalence of footrot was 96%. There was a significant
      age effect, with average score increasing from 9.1 +/- 0.8 in 2-year-old ewes, to
      13.4 +/- 0.9 in 7-year-old ewes. Ewes that lost their lambs tended to have higher
      scores than those that either failed to lamb or successfully reared their litter.
      Significant differences in footrot score were caused by the lambing paddock in
      which the ewes had been, during the period seven weeks to one week before
      infection. Among lambs, aged about 20 weeks, the average footrot score was lower
      (5.0), as was the prevalence (75%). The score increased by an average of 0.09 +/-
      0.03 per day of age and the prevalence increased by an average of 0.6% +/- 0.3%
      per day of age. Lambs born and reared as twins had significantly lower scores
      than singles, and progeny of maiden dams had lower scores than progeny of older
      ewes. There was no significant difference because of the sex of the
      lamb.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257314
TI  - Veterinary education in the world--changing attitudes.
AB  - Veterinary educators all over the world are concerned about the explosion in
      knowledge and about the way veterinary science is taught at present. How can we
      produce veterinarians who will provide the sort of care that will be expected in
      the year 2000 and beyond? In the recent past many schools have increased the
      information presented in their courses without removing any material. Student
      stress has increased, and under-graduates do not retain what they are taught. The
      type of assessment that is currently used often requires regurgitation of 'facts'
      rather than the solution of problems. This paper considers some of the issues
      that are pertinent to the future of veterinary education and suggests ways in
      which the situation may be improved. There is a need for increased activity by
      the Australian Veterinary Association to convince government that present funding
      is inadequate and that increased funding is urgently needed if we are to produce
      veterinarians of the quality the country will need in the next century.

PMID- 8257315
TI  - Real-time ultrasonography for pregnancy diagnosis and foetal ageing in fallow
      deer.
AB  - Three groups of 15 to 17 adult fallow does with some additional yearling does in
      2 of the groups were treated to synchronize oestrous cycles, and mated. All does
      were scanned by ultrasound at 4 weeks of gestation and at weekly intervals from
      week 7 to week 14 of gestation. Growth rates of 13 foetal and uterine characters,
      which have been used for ageing foetuses of red deer, were similar for adult and
      yearling does and among the 3 groups. Transrectal ultrasound scanning was a
      reliable and accurate means of detecting pregnancy and of ageing foetuses of
      fallow deer during weeks 7 to 17 of pregnancy.

PMID- 8257316
TI  - Abnormalities of foetal fluids in sheep: two case reports.
AB  - Two cases of abnormal accumulation of foetal fluids in sheep are described. In
      the first case, a ewe, at 64 days of pregnancy, had 2 sacs of fluid, one at each
      of the tips of the pregnant and non-pregnant horns. Neither sac contained a
      foetus. The composition of the fluids differed from those of the amniotic and
      allantoic fluids associated with a single foetus. The composition resembled that
      of foetal plasma. We conclude that the 2 sacs were amniotic sacs from conceptuses
      that had been resorbed, and that at this early (0.4) stage of pregnancy, amniotic
      fluid can accumulate in the absence of a viable foetus. The second case was a
      rare case of hydrallantois in a ewe at 100 days of pregnancy. The volume of
      allantoic fluid (1800 mL) was more than 10 times normal. The composition was
      normal, except for high chloride and calcium concentrations and a very low
      creatinine concentration. The foetus and the volume and composition of the
      amniotic fluid were normal. The hydrallantois might have occurred as a result of
      some alteration in function of the allantoic membrane, perhaps as a result of
      altered hormonal status of the ewe.

PMID- 8257317
TI  - Phosphorus supplements and fluorosis in cattle--a northern Australian experience.
AB  - Chronic fluoride toxicosis caused lameness, dental lesions and illthrift in an
      extensive beef cattle herd in northern Australia. Up to 15% of the herd was lame
      and the disease forced the culling of large numbers of cows. The source of
      fluoride was fertiliser-grade monoammonium and diammonium phosphate fed as part
      of a mineral supplement. Large quantities of mineral supplement were provided to
      the cattle because lameness was attributed to phosphorus deficiency, which is
      endemic in the area. Most lameness developed in the late dry season in the post
      lactation phase. Severe lameness was caused by fractured pedal bones.

PMID- 8257318
TI  - Failure of therapeutic vaccination of a bull infected with Campylobacter fetus.

PMID- 8257319
TI  - Colour mutant alopecia in a kelpie x border collie dog.

PMID- 8257320
TI  - A serological survey of dogs, cats and horses in south-eastern Australia for
      leptospiral antibodies.

PMID- 8257321
TI  - In-vitro antibacterial properties of tilmicosin against Australian isolates of
      Pasteurella multocida and Pasteurella haemolytica from cattle.

PMID- 8257322
TI  - Effect of zinc sulphate on diazinon concentrations in dipwash containing
      colloidal clay particles.

PMID- 8257323
TI  - Isolation of Leptospira interrogans serovars hardjo and zanoni from a dairy herd
      in north Queensland.

PMID- 8257324
TI  - Secondary degenerative arthropathy (osteoarthrosis) of the hip joints in ageing,
      free-living koalas.

PMID- 8257325
TI  - Enzootic ataxia in red deer, Cervus elaphus.

PMID- 8257326
TI  - Acute intracerebral haematomas: assessment for possible underlying cause with MRI
      scanning.
AB  - Forty-seven patients presenting with acute intracerebral haematomas between 1989
      and 1992 were retrospectively examined to assess the role of Magnetic Resonance
      Imaging (MRI) in identifying any underlying lesion. None had any prior known
      intracerebral pathology. Magnetic resonance imaging scans were done on a 0.5 T
      unit. Ten patients with an average age of 35 years had angiographically occult
      vascular malformations (AOVM) found by MRI (one with biopsy confirmation). One of
      three cases of glioma, three of three cases with secondary tumour, one case of
      superior sagittal sinus thrombosis with haemorrhagic infarction, one of two cases
      of venous angioma and one case of arteriovenous malformation were detected by
      MRI. Progress computed tomography scans discovered two cases of glioma and
      angiography found a venous angioma and an arterial aneurysm, all undetected by
      MRI. It is concluded that MRI scanning is helpful in detecting underlying AOVM as
      a cause of intracerebral haemorrhage but its role in imaging haemorrhagic tumours
      remains unclear.

PMID- 8257327
TI  - Imaging of the ureters on intravenous urography: does a valsalva help?
AB  - A prospective trial, comparing filling of the ureters on routine urography with
      ureteric filling following a valsalva manoeuvre, was performed. A significantly
      greater length of ureter was filled by the study patients than controls, allowing
      this frequently poorly imaged structure to be visualized more consistently.

PMID- 8257328
TI  - Retrograde venography and colour Doppler imaging of a popliteal venous aneurysm.
AB  - Popliteal venous aneurysms are rare and usually manifest with formation of
      thrombus and embolization to the lungs. The radiological features of a popliteal
      venous aneurysm, without thrombus, initially identified by ultrasound with colour
      Doppler imaging and further investigated with retrograde venography is described.

PMID- 8257329
TI  - Postoperative bile duct strictures: ultrasound and endoscopic retrograde
      cholangiopancreatography/percutaneous transhepatic cholangiography evaluation.
AB  - This retrospective study was undertaken to assess the role of ultrasound (US) and
      to compare it with endoscopic retrograde cholangiopancreatography (ERCP) and
      percutaneous transhepatic cholangiography (PTC) in the evaluation of post
      operative common bile duct (CBD) strictures. Seventy-four patients with
      postoperative CBD strictures were evaluated by ERCP and/or PTC. Of these, US
      scans were available in 52 patients. Ultrasound findings of CBD strictures were:
      proximal dilatation of CBD with smooth tapering stenosis (41%); abrupt cut off of
      CBD (18%); and echogenic nodule, without acoustic shadowing, in 16%. Of the
      remainder, mild proximal dilatation of the CBD was seen in 6%, and 19% of the
      patients had normal US scans.

PMID- 8257330
TI  - Retrograde transpopliteal salvage of the failed antegrade transfemoral
      angioplasty.
AB  - Following unsuccessful conventional antegrade transfemoral angioplasty (six
      occlusions, one stenosis) seven patients underwent retrograde transpopliteal
      catheterization to retrieve the situation. The procedure was successful in five
      patients. The other two patients had small calibre popliteal arteries that went
      into spasm on attempted puncture. Provided the popliteal artery is of adequate
      calibre, the procedure is a relatively straightforward technique recommended for
      retrieval of failed antegrade angioplasty.

PMID- 8257331
TI  - The juxtaphrenic peak (Katten's sign) is produced by rotation of an inferior
      accessory fissure.
AB  - Tenting of the diaphragm (Katten's sign) is a common finding in upper lobe
      collapse or where there is loss of volume. Twenty-nine patients have been
      studied, 12 of these prospectively following upper lobectomy. Division of the
      inferior pulmonary ligament was carried out in these 12 patients. The computed
      tomography findings confirm that this sign is due to an accessory oblique
      fissure.

PMID- 8257332
TI  - Decision making in diagnostic radiology.
AB  - Radiology can be more interesting if the principles of decision making are
      understood and used to the advantage of the radiologist, referring clinician and
      patient. This article seeks to revise the principles that radiologists use
      intuitively. Particular emphasis is placed on the importance of the pre-test
      probability, as it can be shown to: (i) vary with the referral pool of patients;
      (ii) be a major determinant of the amount of additional information gained from
      the test; (iii) alter the sensitivity and specificity of the test; and (iv)
      determine largely the significance of a positive or negative test result. An
      investigation helps a clinician by providing information that will move the
      probability of disease above an action threshold or below its exclusion
      threshold. If this does not occur as a result of one study, another is selected.
      This article also describes the factors involved in such a decision tree
      analysis, as well as discussing the reasons for both selecting a particular
      examination and deciding when a test should not be performed.

PMID- 8257333
TI  - The aboriginal chest: a diagnostic approach to the radiological appearances of
      aboriginal patients of the Northern Territory of Australia.

PMID- 8257334
TI  - The role of endoscopic ultrasonography in the upper gastrointestinal tract: a
      review with illustrative cases.
AB  - In this article the current applications of endoscopic ultrasound in the upper
      gastrointestinal tract and its adnexa, as well as the areas of likely
      development, are reviewed. Illustrative cases are shown from the author's
      experience. Pitfalls and limitations of the technique are also discussed.

PMID- 8257335
TI  - Leukaemia clusters: support for radiation as a cause crumbles.

PMID- 8257336
TI  - Superior vena cava syndrome induced by bronchogenic carcinoma: is this an
      oncological emergency?
AB  - This study was initiated to assess the validity of the traditional view that
      superior vena cava syndrome (SVCS) is a life-threatening condition requiring
      immediate treatment without necessarily obtaining a tissue diagnosis. A
      retrospective review of 6504 patients diagnosed to have lung cancer and treated
      at the Queensland Radium Institute between 1979 and 1991 was performed. From this
      group, 249 patients with well-documented SVCS treated with radiotherapy were
      identified. An analysis with respect to duration of symptoms, time to treatment,
      degree of response and overall survival was performed. Although deaths did occur
      in this series due to associated tracheal obstruction, deaths due to venous
      compression per se were not seen. The response to radiotherapy was generally
      poor, with only 19% of patients achieving a complete resolution of their symptoms
      and signs while 30% of patients had no demonstrable response. The overall
      survival of patients in the study group was 5% at two years. Patients
      demonstrating a complete or partial response to treatment survived significantly
      longer than patients who did not respond at all. The median survival for complete
      responders was 6 months while for non-responders it was 1 month. Although 71% of
      patients had commenced radiotherapy within 24 h of presentation, many patients
      had been experiencing symptoms or signs of SVCS for quite some time. Only 29% of
      patients had experienced symptoms for 7 days or less while 49% of the study group
      had experienced symptoms for over 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257337
TI  - Radiation therapy for early stage seminoma of the testis. Analysis of survival
      and gastrointestinal toxicity in patients treated with modern megavoltage
      techniques over 10 years.
AB  - Seventy-seven patients treated with megavoltage irradiation to the para-aortic
      and/or pelvic nodal areas, for stage I and non-bulky (< 5 cm) stage II seminoma
      of the testis, were studied at the Royal Adelaide Hospital from 1981 to 1990. The
      aim was not only to assess overall and relapse-free survival, but also early and
      late gastrointestinal toxicity in a group of patients treated in a uniform manner
      using modern techniques. The 10 year actuarial survival was 96.1% for all
      patients, being 95.6% for stage I and 100% for stage II. The 10 year actuarial
      complication rate for all late gastrointestinal effects was 9.1%. This consisted
      of a 6.5% risk of peptic ulceration and a 2.6% risk of chronic diarrhoea at 10
      years. At least one acute gastrointestinal effect occurred during radiotherapy in
      the vast majority of patients (90.9%). Analysis of the effect of age (< or = 34
      years vs > 34 years), stage (I vs II) and dose of radiation (< or = 30 Gy vs > 30
      Gy), showed none of these variables to have a significant influence on overall
      survival or on the incidence of late complications. The results of these findings
      are discussed in the light of recent studies of a surveillance policy following
      orchidectomy for stage I seminoma of the testis. Given that gastrointestinal
      toxicity is the major toxicity associated with the treatment of stage I patients,
      the data from this study should assist clinicians and their patients to arrive at
      an informed decision regarding adjuvant radiotherapy.

PMID- 8257338
TI  - Craniopharyngioma and the moustache sign.
AB  - Craniopharyngiomas are common suprasellar tumours but these are rarely associated
      with vasogenic oedema. Because the oedema extends into the optic tracts and optic
      radiations, a characteristic pattern is produced that resembles a moustache. The
      oedema is though to be due to leakage of craniopharyngioma contents. Such a case
      is presented in this communication.

PMID- 8257339
TI  - Ocular involvement in primary central nervous system lymphoma: an increasing
      clinical problem?
AB  - A case of unilateral vitreous relapse in a patient with primary central nervous
      system lymphoma (PCNSL) following sequential systemic chemotherapy and
      radiotherapy is reported. A literature review reveals that ocular involvement may
      occur in up to 15-25% of cases during the course of this disease. Full
      ophthalmological assessment, including slit lamp examination, should be included
      in the routine staging of PCNSL at the time of initial diagnosis and subsequently
      if relapse occurs.

PMID- 8257340
TI  - The dense basilar artery as a sign of basilar territory infarction.
AB  - Three cases of basilar artery territory infarction, in which a dense basilar
      artery was noted, are described. The dense basilar artery was recognized on
      computed tomography (CT) by comparing its density with that of other unaffected
      intracranial vessels. This sign is thought to represent basilar thrombosis or
      embolism and has similarities to the dense middle cerebral artery sign. The dense
      basilar artery is an early sign suggesting basilar territory infarction and its
      use improves the CT detection of basilar territory infarction.

PMID- 8257341
TI  - Unusual complications of pancreatitis.
AB  - The computed tomography (CT) appearances of varying grades of severity of acute
      pancreatitis, and its complications, have been described. Bodywall ecchymosis in
      the periumbilical region (Cullen's sign) and loins (Grey Turner's sign), though
      rare, are frequently mentioned in the clinical literature. Massive, exclusively
      retroperitoneal, involvement is also exceedingly rare. Computed tomography
      depiction of these signs is sparsely documented. The CT documentation, with
      clinicosurgical correlation, of two cases of severe acute pancreatitis with these
      unusual complications, is presented.

PMID- 8257342
TI  - Malignant large-cell non-Hodgkin's lymphoma of the spleen.
AB  - Primary malignant tumours of the spleen are rare, with non-Hodgkin's lymphoma
      being the most common. A case of malignant large-cell lymphoma of the spleen in a
      patient with unexplained splenomegaly, is presented. There are very few previous
      reports on this condition in the radiological literature. The sonographic,
      computed tomographic and angiographic findings are described, with a brief review
      of the literature on this condition. Although there are no specific radiological
      findings to diagnose this condition, it has to be considered in the differential
      diagnosis of a solitary lesion in the spleen.

PMID- 8257343
TI  - Duplex sonography in detection of renal artery stenosis: a simplified approach
      using new parameters.
AB  - A case report illustrating a new investigation for detecting renal artery
      stenosis (RAS) is reported. Colour Doppler ultrasound evaluation of the readily
      accessible intrarenal arteries is a fast and accurate technique. Acceleration
      time and acceleration are the Doppler parameters used for measuring systolic
      upstroke on the waveforms obtained. Prolonged acceleration time (> or = 0.07s)
      and diminished acceleration (< or = 3 m/s2) indicate haemodynamically significant
      stenosis. Intrarenal Doppler ultrasound should provide a safe noninvasive
      screening examination for the detection of RAS.

PMID- 8257344
TI  - Acardiac twins.
AB  - Three cases of twin pregnancy complicated by an acardiac twin are reported. This
      is a rare abnormality of twins. A vascular communication exists between the twins
      and the usually normal twin or so called 'pump' twin may develop cardiac failure
      as a result of perfusion of the abnormal twin. The acardiac twin is, generally,
      grossly abnormal with reduction anomalies, particularly of the upper part of the
      body, and gross oedema. Unless this abnormality is recognized the misdiagnosis of
      fetal death in utero may be made and the complications of the 'pump' twin may not
      be predicted. Three cases are presented with only one survivor.

PMID- 8257345
TI  - Torsion of accessory fallopian tube: ultrasound findings in two premenarchal
      girls.
AB  - The ultrasound findings of two cases of fallopian tube duplication, both of which
      had undergone torsion, are described. Two premenarchal girls were examined with
      ultrasound because of clinical evidence of pelvic pathology. Both were found to
      have complex cystic structures that on surgery and subsequent pathological
      examination were shown to be twisted accessory fallopian tubes. Accessory
      fallopian tubes have been reported to occur in 6-13% of selected patient groups.
      To our knowledge, torsion of an accessory tube has not been reported in the
      literature.

PMID- 8257346
TI  - Thrombolytic therapy in paroxysmal nocturnal haemoglobinuria complicated by
      hepatic vein thrombosis.
AB  - Hepatic vein thrombus is a common and often fatal complication of paroxysmal
      nocturnal haemoglobinuria. Rapid diagnosis with ultrasound, computed tomography
      or venography is required to improve the prognosis. Although heparin is often the
      initial therapy of choice, thrombolytic agents may be more beneficial in the
      early management.

PMID- 8257347
TI  - Fatal Clostridium septicum myonecrosis.
AB  - A 20 year old leukaemic patient with neutropaenia secondary to chemotherapy, who
      developed overwhelming sepsis, myonecrosis, vascular occlusion and necrotizing
      enterocolitis due to Clostridium septicum infection is described. Plain abdominal
      radiographs and a computed tomography scan of the abdomen and pelvis showed gas
      in the retroperitoneal soft tissues. Clostridium septicum septicaemia has a
      recognized association with malignancy and neutropaenia and has a high mortality
      if not diagnosed and treated early. Computed tomography scanning of the abdomen,
      pelvis and head is advised in any patient with a positive C. septicum blood
      culture.

PMID- 8257348
TI  - Case Quiz. Left kidney contained an intra renal haematoma and the bladder a layer
      of blood clot capping the trigone and bladder outlet.

PMID- 8257349
TI  - Low dose teletherapy and tumour response.

PMID- 8257350
TI  - The Wellington waiting list system for radiation therapy.

PMID- 8257351
TI  - Congenital obstruction of the posterior urethra.

PMID- 8257352
TI  - Effect of temperature on the stability of avian influenza virus antigens under
      different storage conditions.
AB  - The combined effect of time and temperature on the stability of two avian
      influenza virus (AIV) isolates concentrated with polyethylene glycol (PEG),
      stored at different temperatures, and used in the preparation of avian influenza
      vaccine was evaluated in turkeys at 24 hr and at 12, 24, 30, 36, and 42 months of
      storage. The differences detected between antibodies raised in turkeys by
      vaccines made from isolates under different storage conditions, times, and
      temperatures were not significant (P > 0.05), especially with vaccines prepared
      from one isolate. Virus recovery rates following challenge studies of vaccinated
      birds were similar. However, birds that were vaccinated twice had lower rates of
      virus recovery from the trachea, lungs, pancreas, and fecal samples following
      challenge infection. The results suggest that if stable isolates of AIV can be
      identified, such isolates can be rapidly concentrated with PEG and stored at -20
      C or -196 C for at least 42 months without any loss of potency in the vaccine
      prepared from these isolates. This would reduce the costs associated with vaccine
      storage and subsequent expiration dates.

PMID- 8257353
TI  - Studies on antigenic relatedness of classic and variant strains of infectious
      bursal disease viruses.
AB  - Antigenic relatedness of six classic and variant strains of serotype 1 infectious
      bursal disease virus (IBDV) and one serotype 2 IBDV was investigated by Western
      blotting and enzyme-linked immunosorbent assay (ELISA) using polyclonal,
      monoclonal, and monospecific antibodies to single viral proteins (VP2 and VP3).
      All virus strains cross-reacted similarly, and the viruses were not
      distinguishable from each other by ELISA or Western blot analysis performed with
      polyclonal or non-neutralizing monoclonal and monospecific antibodies. Non
      neutralizing antibodies against the VP2 (40 kilodaltons) reacted strongly with
      VP2 of classic and variant strains of serotype 1 and reacted weakly with VP2 of
      serotype 2 OH strain. This indicated that common antigens were recognized and
      that these epitopes were not strictly dependent on the native structure of the
      virus.

PMID- 8257354
TI  - Comparative pathogenicity and serogrouping of three Washington isolates of
      infectious bursal disease virus.
AB  - The pathology of three infectious bursal disease virus (IBDV) isolates of
      Washington poultry origin (WA-678, WA-770, and WA-994) and seven other known IBDV
      strains (SAL, D-78, MO, OH, Var-A, 2512, and IM) was studied in 3-week-old
      specific-pathogen-free chickens. Inoculation with IM and 2512 strains resulted in
      illness and death. No clinical signs or mortality were present with WA-678, WA
      770, and WA-994. Macroscopically, bursae were swollen and gelatinous with
      occasional hemorrhages. Isolate WA-994 caused marked bursal atrophy. Isolate WA
      678 elicited moderate bursal pathology. Isolate WA-770 resulted in minimal
      atrophy. Strains IM and 2512 caused severe bursal atrophy, and strains Var-A and
      D-78 caused moderate atrophy. Strains SAL, MO, and OH caused no demonstrable
      bursal atrophy. Results of the cross-neutralization study showed that the three
      isolates were more closely related to serotype 1 than to serotype 2 IBDV.

PMID- 8257355
TI  - Effect of hypobaric hypoxia on slow- and fast-growing chickens fed diets with
      high and low protein levels.
AB  - The occurrence of pulmonary hypertension syndrome in fast-growing broiler
      chickens and slow-growing leghorns was studied. In two similar trials, broiler
      chickens and white leghorns were placed either at low altitude (295 m) or in
      hypobaric chambers (simulated high altitude of 2054 m) and fed either a high-
      (22%) or low-protein (17%) ration. Right ventricular hypertrophy as measured by
      right-ventricle:total-ventricle (RV:TV) weight ratio was used as an indicator of
      pulmonary hypertension. The leghorns did not develop pulmonary hypertension as
      the result of polycythemia induced by simulated high altitude. Compared with low
      altitude broilers and leghorns, broilers reared at high altitude responded with
      significantly higher hematological values and 56% ascites mortality because of
      right ventricular failure from pulmonary hypertension, as measured by an
      increased RV:TV ratio.

PMID- 8257357
TI  - Efficacy of norfloxacin nicotinate treatment of broiler breeders against
      Haemophilus paragallinarum.
AB  - The efficacy of the antimicrobial drug norfloxacin for treating infectious coryza
      was examined in 26-week-old male broiler breeders. Chickens were inoculated in
      the infraorbital sinus with the causal organism, Haemophilus paragallinarum. Four
      experimental groups were set up: control uninfected chickens, infected untreated
      chickens, and infected chickens treated for 5 days with either 20 mg
      norfloxacin/kg body weight or 40 mg norfloxacin/kg body weight. The first
      clinical signs were seen 24 hr postinfection. Of the observed clinical signs,
      sinus edema was ameliorated by the treatment, and the percentage of birds
      presenting sinus edema, sneezing, and increased lacrimation was significantly
      reduced after treatment. Clinical signs disappeared rapidly and were gone by the
      second day of treatment. The other signs disappeared gradually over 2 weeks after
      treatment began. There were no significant differences between the two dosage
      levels. H. paragallinarum was not reisolated from the infected infraorbital
      sinuses of birds treated with the higher dose of the drug, whereas the
      reisolation rate was 17% from those treated with the lower dose and 86% from the
      infected untreated birds.

PMID- 8257356
TI  - IgA, IgG, and anti-Pasteurella multocida antibody levels in bursectomized and/or
      cyclophosphamide-treated turkeys after CU vaccination.
AB  - In bursectomized, cyclophosphamide-treated, and bursectomized/cyclophosphamide
      treated turkeys, IgA, IgG, and anti-Pasteurella multocida were determined before
      and after vaccination with the Clemson University (CU) strain of P. multocida.
      Before vaccination, the average total serum level of IgA was significantly (P <
      0.05) lower in bursectomized and bursectomized/cyclophosphamide-treated turkeys
      than in untreated controls, and the average serum levels of anti-P. multocida
      were significantly (P < 0.05) lower in bursectomized, cyclophosphamide-treated,
      and bursectomized/cyclophosphamide-treated turkeys than in untreated controls.
      After vaccination, average serum IgA levels were still significantly (P < 0.05)
      lower in all treated groups of turkeys than in the untreated controls. Also after
      vaccination, total IgG increased significantly (P < 0.05) only in the
      bursectomized turkeys, and serum anti-P. multocida antibody levels increased
      significantly (P < 0.05) in cyclophosphamide-treated,
      bursectomized/cyclophosphamide-treated, and untreated turkeys. After challenge
      with virulent P. multocida, survivability was significantly (P < 0.05) lower in
      the three treated groups of turkeys than in the untreated groups.

PMID- 8257358
TI  - Monoclonal antibodies to Mycoplasma gallisepticum membrane proteins.
AB  - Monoclonal antibodies (MAbs) were prepared to study the immunogenesis of
      Mycoplasma gallisepticum. Balb/c mice were immunized with M. gallisepticum
      immunostimulating complexes and the supernatant of heterokaryotes screened with
      M. gallisepticum and closely related M. synoviae as antigens in indirect enzyme
      linked immunosorbent assay. All selected MAbs proved to be M. gallisepticum
      species-specific when they were tested against 10 different avian Mycoplasma
      species. After immunoblotting analysis, five polypeptides were identified with
      estimated molecular weights of 110,000, 66,000, 64,000, 56,000, and 50,000. Cell
      membrane localization of the recognized polypeptides was studied by
      immunoelectron microscopy. None of the MAbs inhibited the hemagglutinating
      activity of freshly prepared M. gallisepticum. However, one MAb (B3) specific for
      p56 agglutinated the stained M. gallisepticum antigen in the slide agglutination
      test. Results seemed to correlate with published information on the protein
      composition and agglutinating activity of Mycoplasma gallisepticum.

PMID- 8257359
TI  - Protective immune response to Mycoplasma gallisepticum demonstrated in
      respiratory-tract washings from M. gallisepticum-infected chickens.
AB  - Chickens inoculated with Mycoplasma gallisepticum (MG) produced IgA, IgM, and IgG
      detectable in washings from the upper respiratory tract (URTW; nasal sinuses and
      turbinates) and lower respiratory tract (LRTW; trachea, lungs, and air sacs).
      URTW and LRTW from infected chickens had significant protective effects in a MG
      inoculated tracheal-ring-organ-culture system. Protective effects in vitro
      correlated positively with total MG-specific immunoglobulin titer, but not IgA
      titer, as determined by enzyme-linked immunosorbent assay. URTW and LRTW from
      infected chickens inhibited attachment of MG to tracheal-ring-organ cultures in a
      dose-dependent manner. This suggests that chickens produce a protective immune
      response to MG that locates in the respiratory tract and that attachment
      inhibition may be responsible for this protective effect.

PMID- 8257360
TI  - Inhibition of Mycoplasma gallisepticum growth and attachment to chick tracheal
      rings by antibodies to a 64-kilodalton membrane protein of M. gallisepticum.
AB  - A Mycoplasma gallisepticum (MG) strain R protein of 64 kilodaltons (p64) was
      partially digested from the surface of the bacterium by trypsin. Monospecific
      polyclonal anti-p64 IgG inhibited attachment of MG to chick tracheal rings by as
      much as 69%. However, trypsin treatment of viable MG cells did not reduce
      attachment to tracheal rings or hemagglutination titer. Anti-p64 IgG inhibited
      growth of MG strain R in broth and on solid media, inhibited the uptake of
      radiolabeled thymidine, but did not inhibit hemagglutination. Anti-p64 IgG
      inhibited growth of eight MG strains on solid medium. The degree of growth
      inhibition varied widely depending on the strain and correlated positively with
      the reported virulence of the MG strains with one exception (A5969). An IgG
      monoclonal antibody to p64 (MyG 001) inhibited growth of MG strain R on solid and
      in broth media. The strong attachment-inhibition activity of anti-p64 IgG may
      result from its growth-inhibiting activity. Sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis of MG strains suggested that p64 is expressed in higher
      amounts in vitro in virulent strains (R, S6) than in strains of low virulence (F,
      M876, K503, K703, K730). P64 should be used to immunize chickens to determine if
      it can stimulate a growth and attachment-inhibiting response in the respiratory
      tract.

PMID- 8257361
TI  - Serotypes of Salmonella isolated from California turkey flocks and their
      environment in 1984-89 and comparison with human isolates.
AB  - Serotypes of Salmonella from turkeys and their environment identified at the
      California Veterinary Diagnostic Laboratory System (CVDLS) between 1984 and 1989
      are reported. Between 1988 and 1989, Salmonella serotypes from turkeys were
      compared from two sources: from routine submissions to the CVDLS (primarily
      associated with the National Poultry Improvement Plan), and from a random sample
      of turkey farms conducted by the National Animal Health Monitoring System
      (NAHMS). Serotype isolation frequencies were ver similar under these two systems.
      Serotypes identified most frequently under both systems were (listed from most to
      least frequent): Salmonella kentucky, S. anatum, S. heidelberg, S. reading, and
      S. senftenberg. This isolation pattern was different from that found in humans in
      California; only S. heidelberg was relatively common in both humans and turkeys
      during this period.

PMID- 8257362
TI  - Early chick mortality associated with rupture of the yolk sac.
AB  - Rupture of the yolk sac was identified in leghorn chicks from six placements of a
      commercial hatchery that had high mortality (up to 3%) during the first 3 days.
      The abdomens of these chicks were filled with cloudy yellowish fluid; kidneys
      were swollen, and many chicks also had severe visceral urate deposition (visceral
      gout). No significant bacterial growth was detected. The hatchery had recently
      hired new sexors. After the sexors were cautioned to handle the chicks more
      carefully, the problem abruptly subsided. In an experimental attempt to reproduce
      the condition, a graded series of doses (0, 0.5, 1.0, 2.0, and 4.0 ml) of egg
      yolk were injected intraperitoneally into five groups of twenty 1-day-old chicks.
      Twelve of the 20 chicks that received the 4-ml dose died. They developed swollen,
      pale kidneys and had cloudy yellow fluid in the abdominal cavity, but no visceral
      urate deposition. Only six of the remaining 80 chicks that received lesser doses
      or no yolk died.

PMID- 8257363
TI  - An oligonucleotide probe that distinguishes isolates of low virulence from the
      more pathogenic strains of Newcastle disease virus.
AB  - A synthesized oligonucleotide, termed cleavage probe (NDV-CL), has been designed
      to complement the cleavage-activation site of the fusion gene of the Texas GB
      isolate of Newcastle disease virus (NDV). This oligonucleotide probe, 21 bases in
      length, bound with RNA from velogenic strains of NDV tested in a slot-blot
      hybridization assay. The probe also recognized RNA from the mesogenic strains
      used in this assay, although no signal was observed with RNA isolated from
      lentogenic NDVs or with that from other common avian viruses used as controls.
      This probe did not recognize RNA from isolates of other paramyxovirus serotypes
      (PMV-2 or PMV-3) included in this study. The ability of this probe to distinguish
      lentogenic NDVs, which cause little or no clinical disease, from those strains
      that may produce severe morbidity and/or mortality suggests a potential use for
      the probe in a molecular diagnostic assay.

PMID- 8257364
TI  - Adjuvanticity of dimethyl dioctadecyl ammonium bromide, complete Freund's
      adjuvant and Corynebacterium parvum with respect to host immune response to
      coccidial antigens.
AB  - Immune response of chickens to Eimeria was investigated following immunization
      with coccidial antigens in combination with various immunological adjuvants. The
      adjuvanticity of dimethyl dioctadecyl ammonium bromide (DDA) was comparable to
      that of two other adjuvants known to stimulate cell-mediated immunity: complete
      Freund's adjuvant (CFA) and Corynebacterium parvum. However, DDA is considered
      less toxic than CFA and appeared to evoke longer-lasting immunity than C. parvum.
      In general, intramuscular immunization of chickens with merozoite antigens in DDA
      engendered higher protective immunity than did oral immunization. Immunization of
      chickens with merozoite antigens in CFA, DDA, or C. parvum engendered serum IgG
      and biliary secretory IgA (sIgA) antibody responses, as well as coccidial antigen
      specific T-cell lymphoproliferation responses. This study presents evidence that
      DDA acts as an adjuvant for both coccidia antigen-specific antibody and T-cell
      immunity in the avian system.

PMID- 8257365
TI  - Presence of lesions without virus replication in the thymus of chickens exposed
      to infectious bursal disease virus.
AB  - Specific-pathogen-free (SPF) chickens were exposed to the IM and VA isolates of
      virulent infectious bursal disease virus (IBDV). Both viruses induced rapidly
      progressing lymphoid cell depletion in the bursa. The bursal lesions persisted
      through the observation period of 16 days. The virus-exposed birds also had
      histologic lesions in the thymus. Thymic lesions peaked at 3-4 days
      postinoculation (PI) and then subsided. Immunofluorescence (IF) and antigen
      capture enzyme-linked immunosorbent assay (ELISA) detected abundant viral antigen
      in the bursa, but not in the thymus, of chickens during the first week after
      infection with IM-IBDV or VA-IBDV. This result indicated that the presence of
      histologic lesions in the thymus was not associated with active infection and
      replication of the virus in thymic cells. Inoculation of homogenates of bursal
      and thymic tissues from virus-exposed chickens into embryonated chicken eggs
      revealed the presence of infectious virus from both tissues. We speculated that
      the virus recovered from thymus may have been contributed by virus-infected cells
      that were circulating through the thymus at the time when this tissue was
      homogenized.

PMID- 8257366
TI  - Characterization of a group D rotavirus.
AB  - A rotavirus isolated from the intestinal contents of commercial ring-neck
      pheasant chicks was determined to be a group D rotavirus based on its RNA
      electropherotype and its serologic relatedness to known turkey group A and D
      rotaviruses using immune electron microscopy and agar-gel immunodiffusion assays.
      Further characterization revealed a buoyant density in cesium chloride of 1.347
      g/cm3 for double-shelled particles and 1.365 g/cm3 for single-shelled particles.
      The average size for the pheasant-origin group D rotavirus was determined to be
      80 nm for double-shelled particles and 70 nm for single-shelled particles. In
      contrast, the average size for a turkey group A rotavirus isolate was determined
      to be 73 nm for double-shelled particles and 60 nm for single-shelled particles.
      There was no evidence of viral replication by the pheasant-origin group D
      rotavirus (either cytopathic effect or increase in numbers of viral particles)
      after six passages in MA104 cells. The hemagglutinating activity of the pheasant
      origin group D rotavirus was compared with that of a turkey origin group A
      rotavirus. Differences and similarities were noted depending upon the species of
      erythrocytes employed and the temperature of incubation.

PMID- 8257367
TI  - Cellular defense of the avian respiratory system: dose-response relationship and
      duration of response in intratracheal stimulation of avian respiratory phagocytes
      by a Pasteurella multocida bacterin.
AB  - In experiments analyzing dose-response, intratracheal inoculation of chickens
      with 10(8) and 10(9) avirulent Pasteurella multocida organisms induced the
      migration within 24 hr of large numbers of respiratory lavage cells (RLC) with
      increased phagocytic proportions and phagocytic capacity. Doses from 10(4) to
      10(7) organisms per bird resulted in elevated numbers of RLCs that were not
      significantly higher (P > 0.05) than values of uninoculated or mock-inoculated
      control chickens. When analyzing the duration of response, we found that
      inoculation with 10(9) organisms resulted in significantly higher (P < 0.05)
      numbers of RLCs for 63 to 89 hr without significant elevation in phagocytic
      proportion and capacity. The numbers of RLCs were elevated, although not
      significantly (P > 0.05), up to 11 days after inoculation. These results indicate
      that RLCs migrate to the respiratory tract only in response to a relatively high
      number of stimulating bacterial organisms and that the duration of response is
      relatively short. Although there were elevated numbers of RLCs beyond 89 hours
      after stimulation, the question remains as to whether these cells would enhance
      nonspecific defense of the respiratory system of chickens.

PMID- 8257368
TI  - Effect of spectinomycin on Escherichia coli infection in 1-day-old ducklings.
AB  - Two challenge trials and one confirmation trial were conducted to evaluate the
      efficacy of spectinomycin in the treatment of 1-day-old ducklings infected with
      Escherichia coli. In the challenge trials, ducklings were injected in the right
      posterior thoracic air sac with 0.2 cm3 of broth containing 10(8) colony-forming
      units E. coli (strain O78, E38)/ml. Spectinomycin at dosage levels of 2.5 mg, 5.0
      mg, and 10.0 mg of activity was injected subcutaneously 6 hours following
      infection. The confirmation trial was conducted to confirm the challenge trials;
      procedures were similar to those used in the challenge trials, except that only
      the 5.0 mg of activity dosage of spectinomycin was used. In both types of trials,
      spectinomycin-treated ducklings had significantly lower mortality and higher
      average weight gain, average daily gain, and feed consumption than infected
      unmedicated controls. These results indicate that spectinomycin is effective in
      treating ducks for experimentally induced colibacillosis caused by E. coli
      (strain O78, E38).

PMID- 8257369
TI  - A monoclonal antibody-based latex bead agglutination test for the detection of
      Bordetella avium.
AB  - The purpose of this study was to develop a rapid method to distinguish Bordetella
      avium from closely related Bordetella avium-like and B. bronchiseptica bacteria.
      A monoclonal antibody of the IgM isotype was produced in Balb/c mice against live
      B. avium strain 75. The monoclonal antibody, in the form of ascites fluid, was
      added to a bovine serum albumin-glycine buffer (pH 8.6) and adsorbed to 3.03
      microns-diameter latex beads. Optimum concentrations of antibody, beads, and
      bacteria were determined. The latex bead conjugate was tested against 40 isolates
      of B. avium, 24 isolates of B. avium-like bacteria, 17 isolates of B.
      bronchiseptica, two isolates of Alcaligenes faecalis, and several other common
      genera. Strong agglutination occurred with all B. avium isolates and the two
      isolates of A. faecalis. Weak agglutination occurred with Staphylococcus aureus
      and two isolates of B. bronchiseptica. There was no agglutination with any of the
      B. avium-like isolates. The latex bead agglutination test may be useful as an aid
      in the identification of B. avium when used in conjunction with other criteria.

PMID- 8257370
TI  - Comparative evaluation of tissue trophism characteristics in turkeys and mallard
      ducks after intravenous inoculation of type A influenza viruses.
AB  - Ten avian type A influenza viruses consisting of seven waterfowl-origin, one
      pheasant-origin, and two turkey-origin viruses were evaluated for their
      pathogenicity potential after intravenous inoculation into domestic turkeys and
      mallard ducks (Anas platyrhynchos). The replicative abilities and tissue trophism
      properties of each virus isolate were examined in both species. The overall virus
      isolation rate and histopathological lesion score were greater in the turkeys
      than in the ducks. The waterfowl-origin viruses caused more tissue damage in
      turkeys than in ducks but had a narrower tissue distribution range. The pheasant
      isolate was extremely pathogenic in turkeys but had limited distribution and
      little effect in ducks. The turkey isolates were more pathogenic in turkeys than
      in ducks. The pancreas was the most severely affected organ in turkeys, followed
      by kidney and liver. The spleen and bursa were the most commonly affected organs
      in ducks.

PMID- 8257371
TI  - Pathogenicity of Pasteurella multocida: its variable nature demonstrated by in
      vivo passages.
AB  - Pasteurella multocida serotype 3,4 was isolated from a dead turkey, and the
      variable nature of its pathogenicity was demonstrated after in vivo passages. The
      original isolate was encapsulated, and its mean infectious dose (ID50) was higher
      than 10(8.2) colony-forming units (CFU). To increase virulence, the organism was
      passaged intravenously in turkeys. After five passages, the encapsulated organism
      caused 67% mortality with a 10(2) CFU dose, and 50% of the contact control birds
      also died. A non-encapsulated variant that developed from the original isolate
      resulted in no mortality, even at a dose as high as 10(9) CFU. After four
      intratracheal passages, however, the virulence of the non-encapsulated variant
      increased (ID50 approximately 10(6) CFU), despite no apparent change in its
      morphological characteristics. These results suggest that both encapsulated and
      non-encapsulated forms of P. multocida can increase their pathogenicity by bird
      to-bird transmission in a short period of time.

PMID- 8257372
TI  - Rapid and quantitative assay system for measuring anti-infectious bursal disease
      virus antibody using monoclonal antibody bound to polystyrene latex microspheres.
AB  - A monoclonal antibody (MAb) to infectious bursal disease virus (IBDV) that has
      virus-neutralizing activity was bound to polystyrene latex microspheres The
      microspheres agglutinated with extracts of bursae from chickens infected with
      IBDV. Agglutination was inhibited in a competitive manner by adding serum
      obtained from IBDV-infected chickens. The level of agglutination-inhibition
      depended on the serum antibody titer against IBDV. The reaction was visually
      accomplished within 5 minutes. The titer of this rapid assay showed a close
      relationship with that of the virus-neutralization test.

PMID- 8257373
TI  - Biological and molecular characterization of H13N2 influenza type A viruses
      isolated from turkeys and surface water.
AB  - The pathogenicity potential of two H13N2 influenza viruses, one isolated from
      turkeys and the other isolated from surface water, was evaluated in turkeys,
      chickens, and mallard ducks (Anas platyrhynchos) after intracranial and
      oculonasal inoculation. Both isolates replicated in turkey poults, causing
      depressed weight gain, morbidity and mortality; both also caused
      histopathological lesions, such as mild to severe pancreatitis, hepatitis, and
      nephritis in turkeys. These isolates replicated in mallard ducklings but not in
      chickens. There was depressed weight gain in ducklings given the H13N2 isolate
      from water. Neither isolate caused morbidity or mortality in ducklings or chicks
      after inoculation.

PMID- 8257374
TI  - Correlation of circulating antibody and cellular immunity with resistance against
      Cryptosporidium baileyi in broiler chickens.
AB  - The correlation of circulating antibody and cell-mediated immunity (CMI) with
      resistance to Cryptosporidium baileyi was studied using hormonal and chemical
      bursectomy in the one experiment and cyclosporin A in a second experiment. In
      Expt. 1, there was no correlation between antibody (confirmed by enzyme-linked
      immunosorbent assay) and resistance to infection as measured by body weight,
      gross lesions, morbidity, and mortality. Bursectomy altered antibody production,
      but not CMI, as measured by the delayed-type hypersensitivity skin reaction. In
      Expt. 2, cyclosporin A reduced CMI, but not antibody production. Chicks treated
      with cyclosporin A were more susceptible to C. baileyi (more severe respiratory
      disease) than untreated controls. Results suggested that CMI is more important in
      resistance to C. baileyi than circulating antibody.

PMID- 8257375
TI  - Isolation of Salmonella from chickens reacting in the pullorum-typhoid
      agglutination test.
AB  - Over a 3-year period, 134,171 serum samples were screened by the pullorum-typhoid
      tube agglutination test. Of the 680 (0.5%) reactors, Salmonella organisms were
      isolated from 226 of the chickens. Thirteen serotypes of Salmonella were
      isolated. The predominant serotypes were heidelberg, pullorum, kentucky,
      saintpaul, and enteritidis, and they were isolated from 60%, 18%, 5%, 4%, and 3%
      of the chickens, respectively. Salmonella were isolated from the ceca of 161
      chickens, the cecal tonsils of 148 chickens, the organ pool of 150 chickens, and
      the ovary-oviduct pool of 110 chickens. Delayed secondary enrichment was required
      to isolate Salmonella from 36 (15%) of the 226 Salmonella-positive chickens and
      to detect 20% of the total isolations.

PMID- 8257376
TI  - Development of an enzyme-linked immunosorbent assay for the serological diagnosis
      of big liver and spleen disease.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for the serological
      diagnosis of big liver and spleen (BLS) disease. The test utilizes a soluble, BLS
      specific antigen that can be recovered from the livers of infected hens and that
      is known to react in the agar gel immunodiffusion (AGID) test. For use in ELISA,
      the BLS-specific antigen is fractionated by gel filtration chromatography and
      immobilized on microtiter plates using glutaraldehyde. The ELISA was evaluated
      using sera from infected and uninfected flocks originating in the United Kingdom
      and the United States. An ELISA format that incorporated control antigen
      recovered from the livers of uninfected birds for each serum tested was found to
      be more sensitive than the AGID test. A less sensitive but more cost-effective
      format that did not incorporate this control is considered suitable for large
      scale flock screening programs.

PMID- 8257377
TI  - Chlamydia latex agglutination antigen and protocol improvement and psittacine
      bird anti-chlamydial immunoglobulin reactivity.
AB  - Latex agglutination detection of chlamydial antibody activity in psittacine bird
      sera was significantly more sensitive when an improved protocol was followed than
      was a test using the previously used protocol. Titers of antibody-positive sera
      were fourfold to 32-fold higher by the improved protocol than titers by the
      previously used protocol, whereas antibody-negative sera were negative by both
      protocols. Column chromatography was used to separate immunoglobulins in
      psittacine bird serum. Immunoglobulin M was reactive in latex agglutination (LA)
      but non-reactive in direct complement fixation (DCF). Immunoglobulin G was
      reactive in LA and DCF. The fifth supernatant fluid of serum multiply absorbed
      with latex beads was non-reactive in LA and DCF. The immunoglobulins reactive in
      LA had high avidity and affinity for latex beads. Prolonged storage at 4 C to 6 C
      preserved LA reactivity of absorbed immunoglobulins better than storage at 21 C
      to 23 C.

PMID- 8257378
TI  - Antibody detection in matched chicken sera and egg-yolk samples by commercial
      enzyme-linked immunosorbent assay kits for Newcastle disease virus, infectious
      bronchitis virus, infectious bursal disease virus, and avian reovirus.
AB  - ELISA kits have been used to detect antibody in egg yolk. The major advantage
      eggs offer over blood samples is the ability to collect samples without
      compromising flock biosecurity. A disadvantage to using egg yolk over sera
      concerns the method of preparing yolk for antibody testing. The technique used in
      this study involved a simple dilution method with no mixing or extraction. To
      determine the adequacy of yolk samples to replace serum samples, a serum sample
      and the first six eggs were obtained from each of 50 commercial leghorn hens.
      Mean titers were consistently larger for serum than for yolk, but the size of the
      difference varied with the virus. The variation of mean egg titer was comparable
      to that of the serum titer. Correlations between a hen's serum titer and the mean
      titer from hen eggs were only moderate, ranging from 0.35 to 0.85 across viruses
      and systems. The ability to predict the serum titer of a single hen by the mean
      titer from hen eggs may be inadequate.

PMID- 8257379
TI  - Chicken heterophil chemotaxis using Staphylococcus-generated chemoattractants.
AB  - Heterophil chemotaxis, in response to chemotactic factors generated by three
      different strains of staphylococcal bacteria, was measured using the modified
      Boyden-chamber technique. Heterophils were obtained from healthy 6-to-8-week-old
      broiler chickens. Each bacterial strain generated factors that were chemotactic
      for chicken heterophils. Factors generated by two pathogenic isolates of
      Staphylococcus aureus, however, induced significantly greater chemotaxis in
      chicken heterophils than those generated by a nonpathogenic Staphylococcus
      isolate.

PMID- 8257380
TI  - Focal dermatitis and cellulitis in broiler chickens: bacteriological and
      pathological findings.
AB  - Involvement of aerobic bacteria, especially Escherichia coli, in lesions of
      cellulitis in broiler chickens was investigated. Samples of subcutaneous caseous
      material for bacteriological examination were collected aseptically at the
      slaughterhouse from 109 broilers with lesions. Skin tissue was taken from five of
      these birds for histopathological examination. In 96 of the 109 (88.1%) broilers
      sampled, E. coli was isolated from the lesion, and in 60 of these birds it was
      the only bacterial species found. In 33 broilers, Streptococcus dysgalactiae was
      found along with E. coli. Although serotype O78 was isolated the most frequently,
      numerous other serotypes were found; no correlation could be established between
      the size of the lesions and the serotype isolated. The microscopic lesions were
      characterized by thickening of the dermis with a granulomatous inflammatory
      reaction. This study confirms the frequent association of E. coli with cellulitis
      lesions in broiler chickens and reports the frequent isolation of S. dysgalactiae
      from the lesion.

PMID- 8257381
TI  - Effect of an H5N1 avian influenza virus infection on the immune system of mallard
      ducks.
AB  - Avian influenza virus (AIV) of waterfowl origin, A/Mallard/Ohio/184/86 (H5N1),
      was used to evaluate the effect of AIV infection on the functional capabilities
      of the immune system in mallard ducks. The three main arms of the immune system-
      humoral, cell-mediated, and cellular--were evaluated. The integrity of the
      humoral immune system after AIV infection was evaluated by measuring total
      immunoglobulin and IgG antibody production to sheep erythrocytes and Brucella
      abortus antigen using hemagglutination and microagglutination assays,
      respectively. Cell-mediated immunity was evaluated using mitogen/antigen
      stimulation assays, and by measuring the cutaneous basophilic hypersensitivity
      response to intradermal phytohemagglutinin-P inoculation. The cellular component
      of the immune response was evaluated using whole-blood chemiluminescence and
      bacterial clearance assays. Results showed that infection with this AIV isolate
      suppressed T-cell function and enhanced macrophage phagocytic activity.

PMID- 8257382
TI  - Clinical Mycoplasma gallisepticum infection in multiplier breeder and meat
      turkeys caused by F strain: identification by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, restriction endonuclease analysis, and the
      polymerase chain reaction.
AB  - In February 1991, a flock of North Carolina multiplier breeder turkeys
      experienced respiratory signs, sinusitis, airsacculitis, and increased mortality.
      Mycoplasma gallisepticum (MG) was isolated, and appropriate control measures were
      initiated. Ultimately, this outbreak involved several breeder flocks of an
      integrated turkey production company before the last infected flock was
      identified in May 1991. During this time, MG was also isolated from a flock of
      commercial layer-type chickens raised as pullets in close proximity to the index
      turkey flock. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      restriction endonuclease analysis indicated that these isolates were identical to
      each other and to examples of the vaccinal F strain. Additionally, MG isolates
      from the affected turkey breeder and layer flocks were identified as MG F strain
      by use of an F strain-specific DNA probe and polymerase chain reaction. A
      separate outbreak of MG disease in several meat-turkey flocks of a Midwest
      producer/processor yielded isolates identified as F strain by the polymerase
      chain reaction. These studies demonstrated: 1) the utility of newer technologies
      for disease outbreak investigations; and 2) the potential of MG F strain to cause
      disease in breeder and meat turkeys under field conditions.

PMID- 8257383
TI  - Decreased cell-mediated immunity and lack of skeletal problems in broiler
      chickens consuming diets amended with fusaric acid.
AB  - Young female broiler chickens fed diets amended with 0, 35, 75, and 150 mg
      fusaric acid (FA)/kg diet for 3 weeks showed no aberrations in behavior, feed
      intake, weight gain, or appearance of the visceral organs. Furthermore, there was
      no correlation between the dietary concentration of FA and incidence of tibial
      dyschondroplasia and leg-shape deformities. Ash content of dry fat-free tibiae
      was not influenced by FA; thus, no rickets was present in these chickens. FA
      enhanced the humoral response to sheep erythrocytes but significantly reduced
      cell-mediated cutaneous response to phytohemagglutinin-P.

PMID- 8257384
TI  - Histologic and morphometric examination of avian glomeruli from normal and
      swollen kidneys of broilers at slaughter.
AB  - Normal and abnormal kidneys collected from broiler chickens at slaughter (6 to 7
      weeks of age and of mixed sex) were evaluated to establish histopathologic and
      morphometric parameters for broilers. Normal kidneys (group D) had an overall
      mean glomerular diameter of 67.4 +/- 27.8 microns. Abnormal groups (Groups A, B,
      and C) had an average glomerular diameter of 75.2 +/- 32.1 microns, which was
      significantly different (P < 0.01) from that of Group D. All glomerular diameters
      in Group A (otherwise normal birds with swollen kidneys) were significantly
      different (P < 0.01) from corresponding diameters in Group D. In Group B (birds
      condemned for Marek's disease virus), only the mammalian glomeruli were
      significantly different from Group D mammalian glomeruli (P < 0.01). A
      significant increase in glomerular density was observed for all abnormal groups
      and glomerular types. The data indicate that glomerular diameter and cellularity
      might be practical and sensitive indicators of early glomerular changes that can
      occur in grossly swollen kidneys. Increased glomerular density indicates tubular
      loss or increase in glomerular numbers.

PMID- 8257385
TI  - Detection of Mycoplasma gallisepticum infection in field samples using a species
      specific DNA probe.
AB  - Species-specific DNA probes for Mycoplasma gallisepticum (MG) were compared with
      serologic and isolation procedures as a routine diagnostic tool on field
      specimens acquired from chicken flocks experiencing egg-production losses and
      suspected of MG infection. The MG DNA probe clearly identified MG directly from
      tracheal specimens within 2 days, unlike the 7 to 10 days required for culture
      procedures. Cross-reaction of MG with M. synoviae continues to be a stumbling
      block in the serum plate agglutination test.

PMID- 8257386
TI  - Influence of enrichment incubation time on the isolation of Salmonella.
AB  - The optimum incubation times for Salmonella enrichment cultures were determined
      by inoculation of enrichment broths onto plating media after 24 hours at 37 C,
      after 48 hours at 37 C, after a 3-day delayed secondary enrichment (DSE), and
      after a 5-day DSE procedure. The results showed a step-wise increase in
      Salmonella isolations with the longer incubation times. Inoculation of the
      enrichment broths onto plating media after 24 hours incubation followed by a 5
      day DSE made possible the detection of 96% to 98% of the Salmonella-positive
      samples and was the best combination of conditions.

PMID- 8257387
TI  - Monoclonal antibodies species-specific to Mycoplasma gallisepticum and M.
      synoviae.
AB  - Two species-specific monoclonal antibodies (MAbs) were produced against
      Mycoplasma gallisepticum and M. synoviae. The MAb against M. synoviae recognizes
      an antigen of 90,000 molecular weight present in strain WVU 1853 and in two
      Brazilian field isolates. The MAb produced against M. gallisepticum recognizes a
      surface antigen in strains S6 and R and in three Brazilian field isolates of
      different molecular weights. The MAbs do not recognize antigens in M. gallinarum
      and M. iowae.

PMID- 8257388
TI  - Tyzzer's disease in a neonatal cockatiel.
AB  - A 4-day-old cockatiel that died suddenly had a pale, mottled liver at necropsy.
      Extensive necrosis and numerous bacilli were present microscopically in the
      liver. The organism was identified as Bacillus piliformis, the causative agent of
      Tyzzer's disease, by special staining and electron microscopy. This is the first
      report of Tyzzer's disease in an avian species.

PMID- 8257389
TI  - Pullorum disease with unusual signs in two backyard chicken flocks.
AB  - Atypical pullorum disease in two backyard chicken flocks occurred as sudden death
      of many adult birds in one backyard chicken flock and chronic wasting with high
      mortality in a second flock. Chicks had been added to both flocks for several
      months before losses occurred. The chicks, which were not affected, came from a
      previously infected hatchery that did not totally depopulate.

PMID- 8257390
TI  - A diprosopus in a domestic chicken embryo.

PMID- 8257391
TI  - Hepatic protoporphyrin accumulation in a broiler chicken.
AB  - Hepatocellular accumulation and biliary excretion of protoporphyrin in a 6-week
      old chicken are described. The affected liver was grossly dark gray to black.
      Histologically, hepatocytes, bile canaliculi, and bile-duct lumina contained dark
      brown granules. These protoporphyrin pigment accumulations were brightly
      birefringent under polarized light. The ultrastructural appearance of granules
      revealed hair-like crystals in a radial arrangement. Extracted levels of
      protoporphyrin in the affected liver were determined to be 630 micrograms per
      gram of wet (frozen) liver. Spectrofluorometric scans of liver extracts and
      sedimented crystals were characteristic of protoporphyrin.

PMID- 8257392
TI  - Staphylococcus hyicus associated with turkey stifle joint osteomyelitis.
AB  - Essentially pure cultures of Staphylococcus hyicus were isolated in moderate to
      high numbers from tibia growth-plate lesions from five of nine turkey hens
      showing clinical signs of stifle joint osteomyelitis. Of the four other tibia
      growth-plate specimens examined, Salmonella sp. and Enterococcus faecalis were
      individually isolated from one bird each, and no bacterial pathogens were
      isolated from the remaining two cases. Staphylococcus aureus, considered the most
      common cause of osteomyelitis in turkeys, was isolated from none of the nine
      birds examined in this flock. These findings suggest a strong association between
      S. hyicus and turkey stifle joint osteomyelitis.

PMID- 8257393
TI  - Pasteurella anatipestifer-like bacteria associated with respiratory disease in
      pigeons.
AB  - Two cases of respiratory disease in pigeons are described. The first case
      involved pneumonia and tracheitis, and the second case involved tracheitis. In
      both cases, unusual gram-negative, non-fermenting, short rod-shaped bacteria were
      recovered along with other microorganisms. The bacteria produced small,
      glistening, gray colonies on blood agar, did not grow on MacConkey agar, were
      unreactive on several biochemical tests, and resembled Pasteurella anatipestifer.
      Neither pigeon isolate was distinguished from P. anatipestifer by biochemical
      tests. However, there were morphologic and growth differences between the pigeon
      isolates and P. anatipestifer. Furthermore, unlike P. anatipestifer, both pigeon
      isolates were sensitive to aminoglycoside antibiotics and to polymyxin B.
      Finally, neither isolate was agglutinated by antisera to 15 serotypes of P.
      anatipestifer. Diagnosticians, especially those who seldom encounter P.
      anatipestifer, might have difficulty distinguishing the pigeon isolates from P.
      anatipestifer because of their close resemblance.

PMID- 8257394
TI  - True hermaphrodites in a flock of Cochin bantams.
AB  - Three birds from a flock of 125 Cochin bantam chickens were true hermaphrodites,
      having both ovarian and testicular tissues. These birds were recognizable by
      their intermediate comb size, intermediate plumage, and spur development. At
      necropsy, the left gonad of all three birds was an ovotestis and the right gonad
      was a testis. Microscopically, both ovarian follicles and seminiferous tubules
      were present within the ovotestes. Chromosomal analysis of lymphocytes from the
      whole blood of the third bird revealed triploid ZZW sex chromosomes. This high
      incidence (2.4%) of hermaphrodism suggests that there may be a hereditary
      predisposition for genetic intersex.

PMID- 8257395
TI  - Cerebral encephalomalacia in commercial turkeys.
AB  - A flock of 9 1/2-week-old commercial tom turkeys experienced high mortality after
      consuming a complete feed containing an unidentified toxic substance. Initially,
      turkeys were found dead. Clinically, the birds were calm and still but became
      hyperexcitable with noise. A small percentage of birds exhibited torticollis,
      opisthotonos, circling, ataxia, and blindness. Findings at necropsy and upon
      microscopic examination were bilaterally symmetrical areas of necrosis of the
      cerebral hemispheres in the area of the neostriatum that were well demarcated
      from the surrounding normal neuropil. A feeding trial with the suspect feed in
      twelve 4-week-old turkey hens induced clinical disease and gross and microscopic
      brain changes similar to those observed in the field case. Analyses for the
      following substances in the suspect feed were either negative or within
      acceptable limits: salt, selenium, furazolidone, monensin, amprolium, 3-nitro-4
      hydroxyphenylarsonic acid, aflatoxin, deoxynivalenol, zearalenone, T-2 toxin,
      ochratoxin, fumonisin, organophosphates, chlorinated hydrocarbons, and
      carbamates. The toxic component of the feed remains unidentified.

PMID- 8257396
TI  - Application of enzyme-immunohistochemistry for the diagnosis of aspergillosis,
      candidiasis, and zygomycosis in three lovebirds.
AB  - Aspergillosis, candidiasis, and zygomycosis were diagnosed in tissues from three
      lovebirds (Agapornis roseicollis) using indirect enzyme-immunohistochemical
      techniques. In these techniques, the first antibody was raised against fungal
      antigen. A second antibody, which was raised in another animal species, was added
      to link the first antibody to enzyme-immunocomplexes. The reactivity of specific
      monoclonal and polyclonal antibodies was visualized by immunoreactivity of
      alkaline phosphatase anti-alkaline phosphatase and peroxidase anti-peroxidase
      immunocomplexes. All three birds examined had dermal candidiasis. In addition,
      one of the birds was diagnosed with concomitant acute ocular aspergillosis, and
      another bird was diagnosed with chronic zygomycotic myocarditis.

PMID- 8257397
TI  - Antibiotic in general surgery: selection, timing and duration of administration.
AB  - A continuous surveillance of hospital acquired infection (HAI) was done in the
      Department of Surgery, Dhaka Medical College Hospital during the period of 1st
      February '90 to 31st March '90. A new antibiogramme was prepared and applied in
      the same unit for chemotherapy and chemoprophylaxis of surgical cases in the
      subsequent six months from April '90 to September '90. The result of this
      selection, timing of administration and the duration of antimicrobial use have
      been described in this report. The antibiotic policy adopted in this study has
      been found to improve the problem of infection in our surgical practice
      substantially. The incidence of HAI has been reduced to 0.5% from 3.9% which was
      seen in our previous study. The median post operative hospital stay has been
      reduced to 15.5 days from 18.5 days in case with HAI and to 8.5 days from 9 days
      without HAI. We conclude that a continuous surveillance of hospital acquired
      infection is necessary to develop an appropriate antibiogramme. The appropriate
      antibiotic should be started at the induction of anaesthesia and may be a part of
      the induction procedure.

PMID- 8257398
TI  - Psychiatric morbidity in cancer patients.
AB  - One hundred and two patients of cancer were studied by two stage screening
      methods to detect the psychiatric morbidity in these patients. The General Health
      Questionnaire (60 item version) was used to detect the psychiatric morbidity. The
      psychiatric diagnosis was made according to DSM-IIIR criteria. Eighty seven
      patients (85.29%) were found to have psychiatric illness, depression being the
      commonest illness (45.10%). Anxiety disorder was present among 18.63% and other
      minor emotional disorders in 21.56%. Fifteen patients (14.71%) were found to be
      free from any psychiatric symptoms.

PMID- 8257399
TI  - Ketamine infusion for postoperative analgesia: a prospective cohort study in
      asthmatics.
AB  - Ketamine, most often used as an anaesthetic agent can provide adequate post
      operative analgesia when delivered in the form of infusion, replacing narcotics,
      which can cause bronchospasm in susceptible individuals. This cohort study was
      undertaken to assess the feasibility of providing complete post operative
      analgesia in asthmatics with ketamine delivered in sub-anaesthetic doses (6.10
      6.41 ugm./kg.-1/min-1). Diazepam (0.97-1.02 ugm./kg.-1/min-1) was delivered from
      the same infusion to eliminate the unwanted effects of ketamine. Ketamine induced
      little alteration in blood pressure while tachycardia was significant (P < 0.05).
      Respiratory functions observed, were favourable for asthmatics. Diazepam helped
      in reducing ketamine induced side effects, but after infusion over long periods
      tendency of cumulation was observed. Complications encountered were minimum with
      more than 93% patient acceptability for this method of analgesia.

PMID- 8257400
TI  - Dissecting microscopic (DM) and light microscopic (LM) study of the intestinal
      mucosa of Bangladeshi population.
AB  - A total of 67 specimens of proximal intestinal mucosa, one from each subject,
      were examined under dissecting microscopy (DM) and light microscopy (LM).
      Majority of the subjects were adults and males. The overall per-oral biopsy
      failure was 13. DM was found to be useful to demonstrate gross villous atrophy.
      It also helped to orientate the specimens properly before fixation for embedding
      and sectioning. DM and LM findings did not concord in 17% of the specimens. In
      all of these specimens the mucosal surface which appeared normal under DM
      revealed grade-2 change under LM. The present study showed that dissecting
      microscopy (DM) of the intestinal mucosa is not an alternative for histologic
      examination under LM. However, scanner of light microscope (SLM) can be used as
      an alternative for DM.

PMID- 8257401
TI  - Effect of high protein carbohydrate free diet on the evolution of diabetes
      mellitus in rats.
AB  - Diabetes was induced in seventy seven Long Evans rats of both sexes by injecting
      streptozotocin (STZ). Some of these diabetic rats were provided with a high
      protein-carbohydrate (HP-CHO) free diet. The diabetic state of the rats on HP-CHO
      free diet was compared with that of the diabetic rats on normal diet and the
      control rats on normal diet. Diabetic state was assessed through the diet
      consumption, body weight changes, urinary glucose loss and blood glucose
      estimation. From the fifth day the rats on HP-CHO free diet showed significant
      reduction of blood glucose level and urinary glucose loss.

PMID- 8257402
TI  - Obsessive intrusive thoughts in nonclinical subjects. Part I. Content and
      relation with depressive, anxious and obsessional symptoms.
AB  - The present study reports on the development and preliminary validation of a 52
      item self-report instrument designed to assess intrusive thoughts, images and
      impulses that are similar to the aggressive, sexual and disease-related thinking
      characteristic of clinical obsessions. Two hundred and ninety-three students
      completed the Obsessive Intrusions Inventory (OII) as well as standard self
      report measures of negative cognitions and obsessive, anxious and depressive
      symptoms. Regression analysis revealed that intrusive thinking was a significant
      and unique predictor of obsessional but not anxious or depressive symptoms.
      Furthermore, intrusive thinking showed a moderate correlation with anxious but
      not depressive cognitions. The results indicate that the intrusive thoughts
      assessed by the OII are distinct from other forms of negative thinking and may,
      in fact, constitute an analogue form of clinical obsessions in nonclinical
      populations.

PMID- 8257403
TI  - Cues to obsessive-compulsive symptoms: relationships with other patient
      characteristics.
AB  - The waxing and waning of symptoms in obsessive-compulsive disorder (OCD) suggests
      that environmental cues may impact on exacerbations of this disorder. Eighty-one
      Ss with OCD completed the Cues Checklist (CCL; Mackenzie, Ristvedt, Christenson,
      Lebow & Mitchell, 1992), a 339-item checklist of rationally-derived cues and
      circumstances that might be expected to elicit or worsen symptoms. Principal
      components analysis revealed four components: household order and organization,
      contamination and cleaning, negative affect, and prevention of harm and checking.
      Total number of cues endorsed and component scores were correlated with other
      characteristics of the disorder, and with the presence of other Axis I and II
      disorders. Patterns of cue endorsement related to standard measures of obsessive
      compulsive content but not to symptom severity. Early-onset Ss endorsed a greater
      number of cues. History of depression, anxiety disorders and Axis II pathology
      related most strongly to scores on the negative affect component. The values and
      limitations of this approach are discussed.

PMID- 8257404
TI  - The role of CS-US contingency in human evaluative conditioning.
AB  - Recent studies suggest that in Pavlovian conditioning, two different processes
      may be operative: signal learning and evaluative learning, resulting in two
      qualitatively different associative structures. Signal-learning is hypothesized
      to be responsible for providing us with genuine predictors (CS) for significant
      events (US). This proposition logically entails that the statistical
      correlational relation, i.e. the contingency between CS and US should be a
      crucial determinant of signal learning. Evaluative conditioning, on the other
      hand, refers to the observation that the mere pairing of neutral with (dis)liked
      stimuli changes the valence of the originally neutral stimuli in a (negative)
      positive direction. As argued elsewhere, evaluative conditioning is probably
      based on the CS acquiring a mere referential value to the US, without any genuine
      CS-US expectancy being involved. From this, it was hypothesized that evaluative
      conditioning might not be dependent on CS-US contingency. Using the standard
      evaluative conditioning paradigm, four different levels of CS-US contingency were
      created on a between-subject base. The overall effect of evaluative conditioning
      was strongly significant, and was not mediated by awareness of the CS-US
      relation. Of crucial importance, this conditioning effect did not interact with
      the level of contingency, supporting the hypothesis that CS-US contingency is not
      a crucial determinant of evaluative conditioning. Moreover, this effect was
      obtained in a situation in which Ss simultaneously evidence to have consciously
      registered quite accurately the different levels of CS-US contingency.

PMID- 8257406
TI  - An experimental study of the relationship between thoughts and eating behaviour
      in bulimia nervosa.
AB  - This study tested the hypothesis that cognitive disturbance has a causal role in
      the maintenance of disturbed eating in bulimia nervosa. Thoughts about eating,
      weight and shape were activated in one group of patients with bulimia nervosa
      (the experimental group) but not in another (the control group). There was an
      increase in negative self-statements in the experimental group following the
      experimental manipulation. Food consumption was then measured in a taste test. As
      predicted, the experimental group ate less in the short term than the control
      group. Contrary to expectations, they did not subsequently report more objective
      bulimic episodes as a consequence of this decreased food intake. They did,
      however, report significantly fewer subjective bulimic episodes.

PMID- 8257405
TI  - Formation of food aversions in cancer patients receiving repeated infusions of
      chemotherapy.
AB  - Patients receiving emetogenic chemotherapy for cancer have been found to develop
      aversions to normal dietary items consumed in close temporal relation to
      treatment administrations. These aversions are presumed to develop via
      conditioning processes as demonstrated in experimental studies of food aversion
      learning. The present study used a prospective, longitudinal design to evaluate
      the possible role of conditioning in the formation of aversions to normal dietary
      items in women receiving adjuvant chemotherapy for breast cancer. Patients were
      monitored for the development of aversions to foods and beverages consumed in the
      24 hr periods before and after each of eight consecutive chemotherapy infusions
      beginning with the initial infusion. Data on the prevalence, course, and
      prediction of aversions to normal dietary items are reported. These results
      pointed to similarities and differences between aversions formed to normal
      dietary items during chemotherapy treatment and aversions formed to taste stimuli
      during experimental conditioning studies. In addition to their theoretical
      significance, results also suggest possible strategies for preventing the
      clinical problem of aversions to normal dietary items in chemotherapy patients.

PMID- 8257407
TI  - Memory in sub-clinical obsessive-compulsive checkers.
AB  - In a series of experiments we extended the research on possible memory deficits
      in subclinical obsessive-compulsive Ss who reported excessive checking. Using a
      variety of memory tests we compared 20 subclinical checkers to 20 Ss without
      obsessive-compulsive symptomatology. Contrary to hypothesis, checkers remembered
      self-generated words better than read words just as much as did normals, but they
      were more likely than normals to report thinking they had studied words that, in
      fact, had not been on the study list. Further, they more often confused whether
      they read or generated the words at study. Checkers did not appear to perseverate
      on already-recalled words on repeated free recall tests any more than did
      normals. However, checkers remembered fewer actions overall and more often
      misremembered whether they had performed, observed, or written these actions.
      Such memory deficits may contribute to the development of excessive checking.

PMID- 8257408
TI  - Compliance during sessions and homework in exposure-based treatment of
      agoraphobia.
AB  - The relationship between compliance with cognitive-behavioral treatment
      instructions and outcome was examined for 56 agoraphobic clients treated with in
      vivo exposure and training in anxiety management strategies. Clients who complied
      more often with anxiety management instructions during treatment sessions tended
      to improve more on a behavioral avoidance test than those who were less
      compliant, but did not differ on three other outcome variables. Compliance with
      instructions for self-directed exposure between sessions was examined in a subset
      of 28 of these Ss. Clients who spent more time doing homework reported
      significantly greater decrements in fear of fear than less compliant clients and
      also tended to report larger changes on avoidance behavior. However, a quasi
      experimental comparison of homework vs no-homework treatment protocols yielded no
      difference in outcome. Less compliant clients were more symptomatic pretreatment
      and rated their therapists as less caring and less self-confident.

PMID- 8257409
TI  - Effects of endorphin blocking on conditioned SCR in humans.
AB  - In order to test the hypothesis that low levels of endogenous opioids
      (endorphins) predispose to strong conditioning effects, female Ss (N = 36) were
      assigned to a placebo group, a low-dose naltrexone group, or a high-dose
      naltrexone group and then underwent a classical conditioning procedure. This
      procedure consisted of an acquisition phase in which all Ss received 5 pairings
      of a CS+ (neutral picture) and a UCS (100 dB white noise). The CS- (neutral
      picture) was never followed by a UCS. During extinction, Ss received 4
      unreinforced presentations of CS+ and CS-. Throughout the experiment, skin
      conductance responses (SCRs) to the CSs and UCSs were recorded. Acquisition was
      successful in that CS+ slides elicited stronger SCRs than CS- slides. However,
      during acquisition, there was no interaction between drug and differential
      response (CS+ vs CS-). During extinction, there was no overall remaining effect
      of conditioning. Again, no evidence was found to suggest that (remaining) effects
      of conditioning were stronger in the naltrexone treated Ss than in the placebo
      Ss. If anything, the opposite seemed to be true with especially high-dose
      naltrexone Ss showing relatively weak conditioning effects.

PMID- 8257410
TI  - Estimating and testing autocorrelation with small samples: a comparison of the C
      statistic to a modified estimator.
AB  - Huitema and McKean (Psychological Bulletin, 110, 291-304, 1991) recently showed,
      in a Monte-Carlo study, that five conventional estimators of first-order
      autocorrelation perform poorly for small (< 50) sample sizes. They suggested a
      modified estimator and a test for autocorrelation. We examine an estimator not
      considered by Huitema and McKean: the C-statistic (Young, Annals of Mathematical
      Statistics, 12, 293-300, 1941). A Monte-Carlo study of the small sample
      properties of the C-statistic shows that it performs as well or better than the
      modified estimator suggested by Huitema and McKean (1991). The C-statistic is
      also shown to be closely related to the d-statistic of the widely used Durbin
      Watson test.

PMID- 8257411
TI  - Macroscopic marital interaction coding systems: are they interchangeable?
AB  - The present study sought to determine the convergent validity of two macroscopic
      marital interaction coding systems: the Marital Interaction Coding System-Global
      and the Global Couple Interaction Coding System. The sample consisted of 40
      couples who completed the Dyadic Adjustment Scale, the Potential Problem
      Checklist and a 30-min problem solving interactional task. Filmed interactions
      were coded by separate teams of observers using the Marital Interaction Coding
      System-Global and the Global Couple Interaction Coding System. Results showed
      that interobserver agreement, as assessed through intraclass correlations, was
      satisfactory for both coding systems. Between-system comparisons revealed that
      convergent validity coefficients were moderate; thus, it seems premature to
      conclude that macroscopic coding systems are interchangeable. Finally, multiple
      regression analyses indicated that both systems contained significant non
      redundant behavioral predictors of marital adjustment. Implications of these
      results are discussed.

PMID- 8257413
TI  - The human phenolsulphotransferase polymorphism is determined by the level of
      expression of the enzyme protein.
AB  - We have examined the expression of platelet phenolsulphotransferase (PST) in 60
      individuals. Using an antibody which recognizes both forms of PST present in man
      (P-PST and M-PST), we determined that the polymorphism of platelet P-PST activity
      is determined by the level of expression of the enzyme protein. The implications
      for susceptibility to adverse drug reactions and chemical carcinogenesis are
      discussed.

PMID- 8257412
TI  - The Na+/H+ exchanger: an update on structure, regulation and cardiac physiology.

PMID- 8257414
TI  - Salmonella typhimurium neuraminidase acts with inversion of configuration.
AB  - When the time course of the hydrolysis of identical solutions of p-nitrophenyl N
      acetyl-alpha-D-neuraminide by Salmonella typhimurium neuraminidase is monitored
      by u.v. and by its optical rotation, the rotation change is synchronous with, or
      even marginally in advance of, the absorbance change. In experiments under the
      same conditions with influenza-virus neuraminidase, known to react with retention
      of configuration [Chong, Pegg, Taylor and von Itzstein (1992) Eur. J. Biochem.
      207, 335-343], the rotation change is much slower than the absorbance change. The
      inverting, presumably single-displacement, mode of action of the S. typhimurium
      enzyme follows from these observations, and the position (92.5% beta) of the
      slowly established mutarotational equilibrium of N-acetylneuraminic acid
      [Friebolin, Kunzelmann, Supp, Brossmer, Keilich and Ziegler (1981) Tetrahedron
      Lett. 22, 1383-1386].

PMID- 8257415
TI  - Phosphohistidine and phospholysine phosphatase activities in the rat: potential
      protein-lysine and protein-histidine phosphatases?
AB  - We have detected phosphohistidine and phospholysine phosphatase activities in rat
      tissue extracts using partially phosphorylated, high-molecular-mass (> 10 kDa)
      polymers of histidine and lysine as substrates. Multiple phosphohistidine- and
      phospholysine-specific phosphatases were present in these extracts based on
      observed differences in heat stability, sensitivity to bivalent metal ions and
      thiol modifying reagents, and/or elution from DE-52 cellulose. The properties of
      these phosphohistidine and phospholysine phosphatases were distinct from those of
      the phosphomonoester-specific protein phosphatases or the N-P phosphohydrolases
      that act on the free phosphoamino acids phosphoarginine, 3-phosphohistidine or
      phospholysine.

PMID- 8257416
TI  - Wortmannin is a potent phosphatidylinositol 3-kinase inhibitor: the role of
      phosphatidylinositol 3,4,5-trisphosphate in neutrophil responses.
AB  - Phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3) is rapidly produced upon
      exposure of neutrophils to the chemoattractant N-formylmethionyl
      leucylphenylalanine (fMLP), and has been proposed to act as a second messenger
      mediating actin polymerization and respiratory-burst activity. Here we present
      evidence that wortmannin, a known inhibitor of respiratory-burst activity, acts
      on PtdIns 3-kinase, the enzyme producing PtdInsP3 from PtdIns(4,5)P2.
      Pretreatment of 32P-labelled human neutrophils with 100 nM wortmannin totally
      abolished fMLP-mediated PtdInsP3 production, raised PtdInsP2 levels, and did not
      affect cellular PtdInsP and PtdIns contents. The inhibitory effect on PtdInsP3
      formation in intact cells was dose-dependent, with an IC50 of approximately 5 nM.
      Similar results were obtained with PtdIns 3-kinase immunoprecipitated by
      antibodies against the p85 regulatory subunit: wortmannin totally inhibited
      PtdIns3P production in immunoprecipitates at concentrations of 10-100 nM (IC50
      approximately 1 nM). These results illustrate the direct and specific inhibition
      of PtdIns 3-kinase by wortmannin. Since agonist-mediated respiratory-burst
      activation is most sensitive to wortmannin (IC50 = 12 nM), this suggests that
      agonist-mediated PtdInsP3 formation is indispensable for this cell response.
      Neutrophils pretreated with wortmannin develop oscillatory changes in F-actin
      content, but actin polymerization in response to fMLP is not inhibited. This, and
      the absence of PtdInsP3 under these conditions, are in agreement with a
      modulatory role for PtdInsP3 in cytoskeletal rearrangements, but imply that
      PtdInsP3 production is not a primary event triggering elongation of actin
      filaments in neutrophils.

PMID- 8257417
TI  - Phosphorylation of the purified cardiac ryanodine receptor by exogenous and
      endogenous protein kinases.
AB  - The ryanodine receptor is the main Ca(2+)-release structure in skeletal and
      cardiac sarcoplasmic reticulum. In both tissues, phosphorylation of the ryanodine
      receptor has been proposed to be involved in the regulation of Ca2+ release. In
      the present study, we have examined the ability of the purified cardiac ryanodine
      receptor to serve as a substrate for phosphorylation by exogenously added
      catalytic subunit of the cyclic AMP (cAMP)-dependent protein kinase (PK-A),
      cyclic GMP (cGMP)-dependent protein kinase (PK-G), or calmodulin-dependent
      protein kinase (PK-CaM). A large amount of phosphate incorporation was observed
      for PK-CaM (938 +/- 48 pmol of Pi/mg of purified channel protein), whereas the
      level of phosphorylation was considerably lower with PK-A or PK-G (345 +/- 139
      and 96 +/- 6 pmol/mg respectively). In addition, endogenous PK-CaM activity co
      migrates with the ryanodine receptor through several steps of purification,
      suggesting a strong association of the two proteins. This endogenous PK-CaM
      activity is abolished by a PK-CaM-specific synthetic peptide inhibitor.
      Endogenous cAMP- and cGMP-dependent phosphorylation was not observed in the
      purified ryanodine-receptor preparation. Taken together, these observations imply
      that PK-CaM is the physiologically relevant protein kinase, capable of
      phosphorylating the channel protein to a minimum stoichiometry of 2 mol of Pi per
      mol of tetramer.

PMID- 8257418
TI  - Thapsigargin inhibits voltage-activated calcium channels in adrenal glomerulosa
      cells.
AB  - Thapsigargin, an inhibitor of the microsomal Ca2+ pumps, has been extensively
      used to study the intracellular Ca2+ pool participating in the generation of the
      agonist-induced Ca2+ signal in various cell types. A dual effect of this agent
      was observed in bovine adrenal zona glomerulosa cells. At nanomolar
      concentrations, thapsigargin stimulated a sustained Ca2+ influx, probably
      resulting from Ca(2+)-store depletion. In contrast, when added at micromolar
      concentrations, thapsigargin prevented the rise in cytosolic free Ca2+
      concentration ([Ca2+]c) induced by K+. This inhibitory effect of thapsigargin on
      voltage-activated Ca2+ channels was confirmed by measuring Ba2+ currents by the
      patch-clamp technique. Both low-threshold (T-type) and high-threshold (L-type)
      Ca2+ channels were affected by micromolar concentrations of thapsigargin.
      Analysis of the current-voltage relationship for T-type channels revealed that
      thapsigargin did not modify the sensitivity of these channels to the voltage, but
      decreased the maximal current flowing through the channels. In conclusion,
      thapsigargin appears to exert a dual effect on adrenal glomerulosa cells. At
      lower concentrations, this agent induces a sustained Ca2+ entry, whereas at
      higher concentrations it decreases [Ca2+]c by blocking voltage-activated Ca2+
      channels.

PMID- 8257419
TI  - Chloroquine inhibits glucose-transporter recruitment induced by insulin in rat
      adipocytes independently of its action on endomembrane pH.
AB  - In adipocytes, stimulation of glucose transport by insulin is mediated largely by
      translocation of the GLUT4 isoform of glucose transporters from an intracellular
      store to the plasma membrane. Most endomembrane compartments are endowed with
      H(+)-pumping ATPases, and the resulting luminal acidification is thought to play
      a role in vesicular traffic. Chloroquine (Clq), a permeant weak base, was used to
      test whether endomembrane pH is an important factor in GLUT4 translocation. Under
      conditions chosen to optimize Clq uptake, the weak base precluded insulin-induced
      GLUT4 translocation and the associated stimulation of glucose transport. Clq also
      effectively dissipated the delta pH of acidic endomembrane compartments, assessed
      fluorimetrically. To define whether the intracellular GLUT4 storage compartment
      is acidic, immunoadsorption and immunoblotting experiments were performed to
      determine whether glucose transporters and vacuolar-type H+ pumps coexist in the
      same membranes. Unexpectedly, H+ pumps were not detectable in vesicles bearing
      GLUT4. Moreover, dissipation of endomembrane delta pH by monensin failed to
      inhibit insulin-stimulated GLUT4 translocation and hexose transport. Finally, the
      inhibitory effect of Clq persisted in the presence of monensin. We conclude that
      GLUT4 resides in an intracellular compartment devoid of H+ pumps. The insertion
      of this compartment into the plasmalemma is not regulated by transmembrane pH
      gradients. Clq impairs the stimulation of glucose transport by blocking
      translocation of GLUT4 by a pH-independent mechanism. Clq may provide a useful
      tool to elucidate the signalling or fusion steps involved in insulin-induced
      GLUT4 translocation.

PMID- 8257420
TI  - Metabolism of endogenous nutrients in islets of Goto-Kakizaki (GK) rats.
AB  - The metabolism of endogenous nutrients was examined in pancreatic islets of
      control and Goto-Kakizaki (GK) rats. At the ultrastructural level, no glycogen
      was found in the islet cells of GK rats, a situation similar to that prevailing
      in normal islets. Likewise, by measuring the output of L-lactate from islets
      first incubated at 16.7 mM D-glucose and then at 2.8 mM D-glucose, no evidence of
      glycogenolysis was found in the islets of GK rats. The production of NH4+ and
      that of 14CO2 from islets prelabelled with either L-[U-14C]glutamine or [U
      14C]palmitate were higher, however, in GK than in control rats. The changes in
      NH4+ and 14CO2 production evoked by D-glucose, by a non-metabolized analogue of L
      leucine (2-amino-bicyclo[2,2,1]heptane-2-carboxylic acid; BCH) and by 3
      phenylpyruvate were qualitatively comparable in control and GK rats. The
      secretory response to these three secretagogues was severely decreased in the
      islets of GK rats. This coincided with an impaired enhancing action of D-glucose
      on the conversion of [2-3H]glycerol into 3HOH. It is concluded that the
      catabolism of endogenous amino and fatty acids in islets is greater in GK than in
      control rats, especially at low D-glucose concentration. This may account, in
      part at least, for the altered secretory response to BCH and 3-phenylpyruvate.
      For glucose-induced insulin release, however, an impaired acceleration of the
      glycerol phosphate shuttle apparently also participates in the secretory defect.

PMID- 8257421
TI  - Correlation between prolactin secretion and Gs protein expression during
      sustained cholera-toxin stimulation.
AB  - We have studied the chronic effect of cholera toxin (CTX) on prolactin synthesis
      and secretion in GH3 pituitary-tumour cells. Time-course analysis showed that
      prolactin secretion increased with time of CTX exposure, reached a peak at 3 h,
      and decreased thereafter. Prolactin synthesis was also shown to be stimulated by
      CTX. The basic and forskolin-stimulated cyclic AMP levels of the CTX-treated
      cells followed a biphasic time response similar to that of prolactin secretion.
      Exposure of cells to CTX for more than 3 h abolished the subsequent CTX-catalysed
      ADP-ribosylation in vitro. Moreover, a significant decrease in the pertussis
      toxin-catalysed ADP-ribosylation was found after cells were exposed to CTX for
      longer than 6 h. Western-blot analysis indicated that the amount of Gs alpha
      (alpha-subunit of Gs) protein increased within 3 h, followed by a gradual
      decrease to 50% of the control level at 24 h. The accumulation of Gs alpha mRNA
      increased within 6 h of CTX exposure, and decreased thereafter to 40% of the
      basal level at 48 h. Our findings that prolonged treatment of CTX induced similar
      patterns of time responses in Gs alpha protein expression, cyclic AMP production
      and prolactin secretion indicate that CTX-induced changes in Gs alpha protein
      levels may be responsible for the cellular response leading to prolactin
      secretion.

PMID- 8257422
TI  - Cytotoxicity of nitric oxide in Fu5 rat hepatoma cells: evidence for co-operative
      action with hydrogen peroxide.
AB  - The NO-releasing compounds 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1),
      sodium nitroprusside (SNP) and S-nitroso-N-acetyl-DL-penicillamine (SNAP)
      mediated a rapid loss of viability of Fu5 rat hepatoma cells. SIN-1 in addition
      to NO also released the superoxide anion radical (O2-.). Its cytotoxicity,
      however, was not affected by superoxide dismutase. In contrast, the H2O2
      converting enzyme catalase significantly, but not completely, diminished cell
      damage, indicating participation of H2O2 in the tumoricidal activity of SIN-1.
      Glucose oxidase (5 m-units/ml), producing similar amounts of H2O2 to 5 mM SIN-1,
      had no effect on cell viability. When 5 m-units/ml glucose oxidase was added to
      incubations with 5 mM SNP, which alone initiated cell injury of about 40%, cell
      damage was significantly increased up to 95%. Similar results were observed with
      1 mM SNAP and 20 m-units/ml xanthine oxidase, which mediated cytotoxicity of
      about 90% when both compounds were added together, compared with 35% and 55% cell
      injury, respectively, induced by the single compounds. The results indicate that
      a co-operative action with H2O2 enhances the tumoricidal activity of NO in Fu5
      cells. No evidence for an interplay of NO with O2-. in cytotoxicity, e.g. via the
      peroxynitrite anion (ONOO-), was found.

PMID- 8257423
TI  - Preparation and characterization of fragments from the N-terminal end of bovine
      serum albumin under native conditions.
AB  - The domain I of BSA, containing residues 1-183 of the protein sequence, was
      isolated by CNBr treatment. It was further reductively cleaved into two
      subfragments, N1 and N2, in 8 M urea; the subfragments were regenerated in GSH
      and GSSG. The fragment N and subfragments N1 and N2 were found to be homogeneous
      with respect to size and charge. Results for amino acid composition, N-terminal
      amino acid sequence, thiol groups and M(r) suggested that the fragments N1 and N2
      contain residues 88-183 and 1-87 of the intact BSA respectively. Optical studies,
      intrinsic-viscosity measurements, gel-filtration data and derived hydrodynamic
      parameters, taken together with the results on proteolytic digestion, showed that
      fragment N, as well as its subfragments N1 and N2, exist in compact and globular
      conformation and that the conformation of N2 fragment is more compact than that
      of the N1 fragment.

PMID- 8257424
TI  - Differential distribution in white and grey matter of tau phosphoisoforms
      containing four tubulin-binding motifs.
AB  - The microtubule-associated protein tau has been isolated and purified from both
      white and grey brain matter. Tau isoforms were fractionated, based on their
      different phosphate contents, by iron-chelating affinity chromatography.
      Differences were observed in the proportions of phosphorylated isoforms of tau
      protein (containing four tubulin-binding motifs) present in white and grey
      matter. In white matter, isoforms containing four tubulin-binding motifs are
      mainly present in a phosphorylated form. Thus there appears to be a correlation
      between the modification, by phosphorylation, of some sites in the tau molecule
      and the subcellular localization (axonal or somatodendritic compartments) of the
      modified isoforms.

PMID- 8257425
TI  - Functional, spectroscopic and structural properties of haemoglobin from chamois
      (Rupicapra rupicapra) and steinbock (Capra hircus ibex).
AB  - The functional and spectroscopic properties of chamois (Rupicapra rupicapra) and
      steinbock (Capra hircus ibex) haemoglobin (Hb) have been studied with special
      reference to the action of allosteric effectors and temperature. Moreover, the
      amino acid sequences of the N-terminal segments of the alpha- and beta-chains
      have been determined. The present results indicate that chamois and steinbock Hbs
      display a low affinity for O2, which appears to be modulated in vivo by Cl- ions
      rather than 2,3-bisphosphoglycerate. The Bohr effect for O2 binding to chamois
      and steinbock Hb is higher than for reindeer and bovine Hbs, being similar to
      that of human Hb. Moreover, the temperature-dependence of oxygenation appears
      intermediate between that of human and reindeer Hbs. E.p.r. and absorption
      spectroscopic properties of the ferrous nitrosylated derivative of chamois and
      steinbock Hbs suggest that both haemoproteins are in a low-affinity conformation
      even in the absence of InsP6. The reduced effect of polyphosphates on the
      functional and spectroscopic properties of chamois and steinbock Hb agree with
      amino acid differences in the N-terminal segment of the beta-chains (i.e. the
      deletion of Val(NA1) and the replacement of His(NA2), present in human Hb, and
      Gln(NA2), present in horse Hb, by Met). The molecular mechanism modulating the
      basic reaction of O2 with chamois and steinbock Hb may be linked to specific
      physiological needs related to the high-altitude habitats of these two animals.

PMID- 8257426
TI  - Activation of NADPH oxidase of human neutrophils involves the phosphorylation and
      the translocation of cytosolic p67phox.
AB  - Activation of human neutrophil NADPH oxidase requires the interaction of
      cytosolic and membrane-associated components. Evidence has been accumulated that
      in phorbol 12-myristate 13-acetate (PMA)-stimulated neutrophils, the
      translocation to the plasma membrane of the cytosolic components p47phox and
      p67phox and the phosphorylation of p47phox are essential steps in activation of
      NADPH oxidase. No direct evidence has been presented to date as to whether
      p67phox is also phosphorylated. To address this problem we have
      immunoprecipitated p67phox from neutrophil cytosol and membrane fractions. The
      results indicate that, very soon after activation with PMA (20 s), p67phox was
      present in a phosphorylated form in the cytosol and in the membranes. At later
      times (1-3 min) the extent of p67phox phosphorylation continuously increased both
      in the cytosol and in the membrane fraction, while oxygen consumption reached the
      maximal rate within 40 s, and then remained linear. p67phox was also
      phosphorylated in formyl-methionyl-leucyl-phenylalanine-activated neutrophils.
      That the phosphorylated p67 protein we identified in immunoprecipitation
      experiments was p67phox was confirmed by the observation that no phosphorylated
      band of 67 kDa was immunoprecipitated from the cytosol and membranes of PMA
      stimulated neutrophils from a p67phox-deficient chronic granulomatous disease
      patient. In this case, p47phox was normally phosphorylated. These data
      demonstrate that: (1) the phosphorylation of p67phox is correlated with
      activation of NADPH oxidase, and (2) continuous phosphorylation of p67phox is
      required in order to maintain the linearity of the respiratory burst.

PMID- 8257427
TI  - Involvement of human plasma angiotensin I-converting enzyme in the degradation of
      the haemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline.
AB  - The degradation of N-Ac-Ser-Asp-Lys-Pro (AcSDKP), a negative regulator
      controlling the proliferation of the haematopoietic stem cell, by enzymes present
      in human plasma, has been investigated. Radiolabelled AcSD[4-3H]KP ([3H]AcSDKP, 1
      mM) was completely metabolized in human plasma with a half-life of 80 min,
      leading exclusively to the formation of radiolabelled lysine. The cleavage of
      AcSDKP was insensitive to classical proteinase inhibitors including leupeptin,
      but sensitive to metalloprotease inhibitors. The degradation was completely
      blocked by specific inhibitors of angiotensin I-converting enzyme (ACE; kininase
      II; peptidyldipeptide hydrolase, EC 3.4.15.1), showing that the first step of the
      hydrolysis was indeed due to ACE. In dialysed plasma, the hydrolysis proceeded at
      only 17% of the maximal rate, whereas addition of 20 mM NaCl led to the recovery
      of the initial rate observed with normal plasma. Hydrolysis of AcSDKP by
      commercial rabbit lung ACE generated the C-terminal dipeptide Lys-Pro. Thus, ACE
      cleaves AcSDKP by a dipeptidyl carboxypeptidase activity. In fact the formation
      of Lys-Pro was observed when AcSDKP was incubated in human plasma in the presence
      of HgCl2. These results suggest that ACE is involved in the first limiting step
      of AcSDKP degradation in human plasma. The second step seems to be under the
      control of a leupeptin- and E-64-insensitive, HgCl2-sensitive plasmatic enzyme.

PMID- 8257428
TI  - 13C n.m.r. isotopomer and computer-simulation studies of the non-oxidative
      pentose phosphate pathway of human erythrocytes.
AB  - 13C double-quantum filtered correlation spectroscopy (DQF-COSY) provides a novel
      method for the detection of reactions involving carbon-bond scissions. We report
      the use of this technique to investigate isotopic exchange reactions of the non
      oxidative pentose phosphate pathway in human erythrocytes. These exchange
      reactions resulted in the formation of a range of isotopic isomers (isotopomers)
      of glucose 6-phosphate after incubation of a mixture of universally 13C-labelled
      and unlabelled glucose 6-phosphate with fructose 1,6-bisphosphate and
      haemolysates. These isotopomers were detected in the coupling patterns of cross
      peaks within the DQF-COSY spectrum of the deproteinized sample. A computer model
      which fully describes the reactions of the non-oxidative pentose phosphate
      pathway in human erythrocytes has previously been constructed and tested with 31P
      n.m.r. time-course data in our laboratory. This model was refined using 13C
      n.m.r. time-course data and extended to include the range of isotopomers which
      may be formed experimentally by the reactions of the non-oxidative pentose
      phosphate pathway. The isotopomer ratios obtained experimentally from the DQF
      COSY spectrum were consistent with simulations generated by this model.

PMID- 8257429
TI  - Structure-activity relationships in the inhibition of serine beta-lactamases by
      phosphonic acid derivatives.
AB  - A new series of phosphonyl derivatives has been prepared and tested for
      inhibition of serine (classes A and C) beta-lactamases. The results were compared
      with those previously acquired with aryl phosphonate monoesters and with alkaline
      hydrolysis rates. A methyl p-nitrophenyl phosphate monoanion was markedly poorer
      as an inhibitor of the class C beta-lactamase of Enterobacter cloacae P99 than a
      comparable p-nitrophenyl phosphonate. Phosphonyl fluorides, thiophenyl esters, N
      phenylphosphonamidates and a p-nitrophenyl thionophosphonate were, in general,
      comparable with p-nitrophenyl phosphonates in inhibitory power. The incorporation
      of a specific amino side chain led to an increase in the rates of inhibition of
      around 10(4)-fold. Apparently unresponsive to the addition of the side chain to
      the enzyme was N-phenyl methylphosphonamidate, where binding of the side chain
      may interfere with access of the leaving group to a proton which is necessary to
      active-site phosphonylation and inhibition. Typical class A beta-lactamases were
      significantly more refractory than the class C enzyme to all of these reagents.

PMID- 8257430
TI  - Purification of highly intact plastids from various heterotrophic plant tissues:
      analysis of enzymic equipment and precursor dependency for starch biosynthesis.
AB  - Starting with a protocol originally developed for the purification of intact
      plastids from cauliflower buds [Journet and Douce (1985) Plant Physiol. 79, 458
      467] we have modified this method to obtain intact heterotrophic plastids from
      etiolated barley leaves (Hordeum vulgare) and pea (Pisum sativum) and maize (Zea
      mays) endosperm. Two subsequent centrifugation steps on Percoll gradients were
      performed, the first as an isopycnic, the second as zonal, centrifugation step in
      a swing-out rotor. Percoll density and centrifugation time were adjusted for the
      various tissues. The obtained plastid preparations are characterized by a low
      degree of contamination with other cellular components and an intactness of at
      least 90%. In isolated maize endosperm amyloplasts, starch synthesis is driven by
      exogenously applied hexose phosphates (glucose 6-phosphate and glucose 1
      phosphate) rather than by dihydroxyacetone phosphate. The hexose-phosphate
      dependent starch synthesis is strictly dependent upon the intactness of the
      plastids and is increased up to 9-fold when ATP and 3-phosphoglyceric acid are
      added to the incubation medium. The occurrence of fructose-1,6-bisphosphatase and
      malate dehydrogenases in some plastid types is discussed in relation to their
      possible role in starch synthesis.

PMID- 8257431
TI  - Correlation of apoptosis with change in intracellular labile Zn(II) using zinquin
      [(2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)acetic acid], a new specific
      fluorescent probe for Zn(II).
AB  - Zinquin [(2-methyl-8-p-toluenesulphonamido-6-quinolyloxy)-acetic acid], a
      membrane-permeant fluorophore specific for Zn(II), was used with
      spectrofluorimetry and video image analysis to reveal and quantify labile
      intracellular Zn. Zinquin labelled human chronic-lymphocytic-leukaemia
      lymphocytes, rat splenocytes and thymocytes with a weak diffuse fluorescence that
      was quenched when intracellular Zn was chelated with NNN'N'-tetrakis-(2
      pyridylmethyl)ethylenediamine (TPEN) and was greatly intensified by pretreatment
      of cells with the Zn ionophore pyrithione and exogenous Zn. There was substantial
      heterogeneity of labile Zn among ionophore-treated cells, and fluorescence was
      largely extranuclear. The average contents of labile Zn in human leukaemic
      lymphocytes, rat splenocytes and rat thymocytes were approx. 20, 31 and 14
      pmol/10(6) cells respectively. Morphological changes and internucleosomal DNA
      fragmentation indicated substantial apoptosis in these cells when the level of
      intracellular labile Zn was decreased by treatment with TPEN. Conversely,
      increasing labile Zn by pretreatment with Zn plus pyrithione suppressed both
      spontaneous DNA fragmentation and that induced by the potent apoptosis-induced
      agents colchicine and dexamethasone. These results suggest that prevention of
      apoptosis is a function of labile Zn, and that a reduction below a threshold
      concentration in this Zn pool induces apoptosis.

PMID- 8257432
TI  - The 50 kDa protein subunit of assembly polypeptide (AP) AP-2 adaptor from
      clathrin-coated vesicles is phosphorylated on threonine-156 by AP-1 and a soluble
      AP50 kinase which co-purifies with the assembly polypeptides.
AB  - AP50 is a subunit of the assembly polypeptide (AP) subclass AP-2 from bovine
      brain coated vesicles. It can be phosphorylated in vivo and in vitro on a
      threonine residue by means of the AP50 kinase activity associated with AP. We
      have undertaken an analysis of the amino acid sequence around the AP50
      phosphorylation site. After phosphorylation in vitro of AP50 followed by tryptic
      cleavage, only one radioactive peptide was isolated following Mono-Q ion-exchange
      f.p.l.c. and reverse-phase h.p.l.c. The amino acid sequence of this peptide:
      Glu146-Glu-Gln-Ser-Gln-Ile-Thr-Ser-Gln-Val-Thr*-Gly-Gly-Ile-Gly-Tr p-Arg162,
      displayed two threonine residues. Analysis of the yield and radioactivity of the
      product from automated Edman degradation indicated that only Thr-156 was
      phosphorylated, reflecting the presence of a single phosphorylation site in AP50.
      AP phosphorylated the corresponding synthetic peptide on the same threonyl
      residue. We demonstrated that AP50 was a phosphorylation substrate unable to
      autophosphorylate. The enzyme involved in the AP50 phosphorylation was shown to
      be associated with AP-1 and with a soluble protein complex co-purified with APs
      but resolved from the latter by hydroxyapatite-column exclusion chromatography.
      This AP50 kinase activity corresponded to a 280 kDa protein complex according to
      gel-filtration data.

PMID- 8257433
TI  - Phosphoglucomutase 1: a gene with two promoters and a duplicated first exon.
AB  - In view of its central role in glycolysis and gluconeogenesis and its polymorphic
      genetic variability, the phosphoglucomutase 1 (PGM1) gene in man has been the
      target of protein structural studies and genetic analysis for more than 25 years.
      We have now isolated genomic clones containing the complete PGM1 gene and have
      shown that it spans over 65 kb and contains 11 exons. We have also shown that the
      sites of the two mutations which form the molecular basis for the common PGM1
      protein polymorphism lie in exons 4 and 8 and are 18 kb apart. Within this region
      there is a site of intragenic recombination. We have discovered two alternatively
      spliced first exons, one of which, exon 1A, is transcribed in a wide variety of
      cell types; the other, exon 1B, is transcribed in fast muscle. Exon 1A is
      transcribed from a promoter which has the structural hallmarks of a housekeeping
      promoter but lies more than 35 kb upstream of exon 2. Exon 1B lies 6 kb upstream
      of exon 2 within the large first intron of the ubiquitously expressed PGM1
      transcript. The fast-muscle form of PGM1 is characterized by 18 extra amino acid
      residues at its N-terminal end. Sequence comparisons show that exons 1A and 1B
      are structurally related and have arisen by duplication.

PMID- 8257434
TI  - Flux control coefficients determined by inhibitor titration: the design and
      analysis of experiments to minimize errors.
AB  - This paper is a study into the effects of experimental error on the estimated
      values of flux control coefficients obtained using specific inhibitors. Two
      possible techniques for analysing the experimental data are compared: a simple
      extrapolation method (the so-called graph method) and a non-linear function
      fitting method. For these techniques, the sources of systematic errors are
      identified and the effects of systematic and random errors are quantified, using
      both statistical analysis and numerical computation. It is shown that the graph
      method is very sensitive to random errors and, under all conditions studied, that
      the fitting method, even under conditions where the assumptions underlying the
      fitted function do not hold, outperformed the graph method. Possible ways of
      designing experiments to minimize the effects of experimental errors are analysed
      and discussed.

PMID- 8257435
TI  - A comparison of Zn(II) and Co(II) in the kinetics of inactivation of aminoacylase
      by 1,10-phenanthroline and reconstitution of the apoenzyme.
AB  - The kinetics of reconstitution of apoacylase with either Zn(II) or Co(II) and the
      inactivation of the Co(II) reconstituted enzyme by 1,10-phenanthroline (OP) has
      been studied by following the substrate reaction continuously in presence of the
      metal ion or OP respectively. Although the native Zn(II)-containing and the
      Co(II)-reconstituted enzymes have closely similar Michaelis constants and maximal
      velocities, the kinetics for both the inactivation by OP and the reconstitution
      of the apoenzyme with the metal ions differs considerably. For Co(II), both the
      inactivation by OP and the reconstitution show simple kinetics, but for Zn(II),
      the inhibition by OP is a multi-phasic process [Wang, Wu, Wang, Zhou and Tsou
      (1992) Biochem. J. 281, 285-290], and the kinetics of reconstitution is also much
      more complicated. Both the native and the Co(II)-reconstituted enzymes are
      inhibited by excess of Zn(II), but not by Co(II). The inhibition by Zn(II) in
      excess and the reconstitution of the apoenzyme with Zn(II) are co-operative
      processes. The inhibition by Zn and its effect on the fluorescence emission of 1
      anilinonaphthalene-8-sulphonic acid bound to the native enzyme indicate multiple
      Zn(II)-binding sites.

PMID- 8257436
TI  - A mutant mouse (tx) with increased hepatic metallothionein stability and
      accumulation.
AB  - Metallothioneins (MTs) are low-molecular-mass cysteine-rich proteins implicated
      in metal homoeostasis and resistance to toxicity induced by heavy metals and
      alkylating agents. We report high hepatic MT protein accumulation (greater than
      100-fold compared with wild-type mice) in toxic milk (tx) mice, along with
      markedly higher cytosol copper and zinc levels. Increased MT-gene transcription
      alone could not account for the high constitutive MT protein levels, since MT
      mRNA levels were not increased in tx mouse livers. However, hepatic MT was
      significantly more stable in adult tx mice: MT half-life (t1/2) was 79 or 77%
      greater than in wild-type mice before and after Cd induction respectively. Cd or
      Zn treatment increased MT mRNA, but not MT protein, accumulation in tx mouse
      livers: Cd displaced MT-bound Zn and Cu in preexisting MT. Thus tx mice appear to
      accumulate hepatic MT as a result of decreased protein degradation. These animals
      may provide a useful model to study the physiological role of MT, and human
      diseases (such as Wilson's disease) with abnormal copper metabolism.

PMID- 8257437
TI  - Characterization of the 3-dehydroquinase domain of the pentafunctional AROM
      protein, and the quinate dehydrogenase from Aspergillus nidulans, and the
      overproduction of the type II 3-dehydroquinase from neurospora crassa.
AB  - The AROM protein of Aspergillus nidulans is a multidomain pentafunctional
      polypeptide that is active as a dimer and catalyses steps 2-6 in the
      prechorismate section of the shikimate pathway. The three C-terminal domains
      (including the type I 3-dehydroquinase) of the AROM protein are homologous with
      the qutR-encoded QUTR protein that represses transcription of the eight genes
      comprising the quinic acid utilization (qut) gene cluster, and the two N-terminal
      domains are homologous with the qutA-encoded QUTA protein that transcribes the
      qut genes. As part of a larger research programme designed to compare the
      structures of the three proteins and to probe the domain structure and
      interaction within each protein, we have overproduced and purified the 3
      dehydroquinase domain of the AROM protein. Additionally we have overproduced and
      purified the qutB-encoded quinate dehydrogenase and overproduced the qa-2 encoded
      type II 3-dehydroquinase of Neurospora crassa. We report that the AROM 3
      dehydroquinase domain has a monomeric native state, with an apparent kcat./Km
      ratio that is approx. 160-fold lower than the value for the native N. crassa AROM
      protein. The AROM protein 3-dehydroquinase domain is sensitive to inactivation by
      borohydride in the presence of the substrate 3-dehydroquinate, confirming that it
      is a typical type I 3-dehydroquinase. The purified quinate dehydrogenase is
      bifunctional, being able to metabolize shikimate as a substrate. The apparent Km
      values for quinate (450 microM), shikimate (1.7 mM) and NAD+ (150 microM) are all
      similar to values reported for the qa-3-encoded enzyme from N. crassa.

PMID- 8257438
TI  - Identification and characterization of a neutral endopeptidase activity in
      Aplysia californica.
AB  - Kidney plasma membranes of Aplysia californica were shown to contain an
      endopeptidase activity which cleaved [Leu]enkephalin (Tyr-Gly-Gly-Phe-Leu) and
      [Leu]enkephalinamide (Tyr-Gly-Gly-Phe-Leu-NH2) at the Gly3-Phe4 bond, as
      determined by reverse-phase h.p.l.c. analysis of metabolites. The optimal pH was
      shown to be 6.5. The bivalent cation chelating agent, 1,10-phenanthroline
      protected [Leu]enkephalin from degradation, suggesting that this enzyme is a
      metallopeptidase. The degradation of [Leu]enkephalin was also abolished by the
      neutral endopeptidase-24.11 inhibitors RB104 (2-[(3-iodo-4-hydroxyl)
      phenylmethyl]-4-N-[3-(hydroxyamino-3-oxo-1- phenylmethyl)-propyl]amino-4
      oxobutanoic acid), HABCO-Gly [(3-hydroxy-aminocarbonyl-2-benzyl-1
      oxypropyl)glycine], phosphoramidon and thiorphan, with IC50 values of 1 nM, 1
      microM, 20 microM and 30 microM respectively. By contrast, the angiotensin
      converting enzyme inhibitor captopril and the serine proteinase inhibitor
      phenylmethanesulphonyl fluoride were without effect. Phase separation experiments
      using Triton X-114 showed that about 64% of the neutral endopeptidase activity in
      the Aplysia kidney membrane corresponds to an integral membrane protein. A
      specific radioiodinated inhibitor ([125I]RB104) was shown to bind the Aplysia
      endopeptidase with high affinity; the KD and Bmax. values were 21 +/- 5 pM and
      20.3 +/- 5 fmol/mg of proteins respectively. This inhibitor was used to determine
      the molecular form of the enzyme, after separation of solubilized membrane
      proteins on SDS/PAGE and transfer on to nitrocellulose membranes. A single
      protein band with an apparent molecular mass of 140 kDa was observed. The
      labelling was abolished by specific neutral endopeptidase inhibitors. This study
      provides the first biochemical characterization of an endopeptidase with
      catalytic properties similar to those of neutral endopeptidase-24.11 in the
      mollusc Aplysia californica.

PMID- 8257439
TI  - Activated protein kinase C binds to intracellular receptors in rat hepatocytes.
AB  - The aim of this study was to identify in rat hepatocytes cellular polypeptides
      that bind protein kinase C (PKC) and may influence its activity and its
      compartmentation. At least seven proteins, with apparent M(r) values between
      12,000 and 36,000, that behave like Receptors for Activated C-Kinase (RACKs) were
      found in the Triton-X-100-insoluble fraction of these cells; i.e. PKC bound to
      these polypeptides when it was in its active form. RACKS seem to be PKC
      substrates. Studies using isotype-specific PKC antibodies suggested some
      selectivity of RACKs, i.e. RACKs in the M(r) approximately 28,000-36,000 region
      bound PKC-alpha and PKC-beta in the presence of phosphatidylserine, diolein and
      Ca2+, whereas those of M(r) approximately 12,000-14,000 bound all isoforms
      studied, and, in contrast with the other RACKs, they did this even in the absence
      of Ca2+. Peptide I (KGDYEKILVALCGGN), which has a sequence suggested to be
      involved in the PKC-RACKs interaction [Mochly-Rosen, Khaner, Lopez and Smith
      (1991) J. Biol. Chem. 266, 14866-14868], inhibited PKC activity. Preincubation of
      RACKs with antisera directed against peptide I prevented PKC binding to them. The
      data suggest that peptide I blocks PKC binding to RACKs by two mechanisms:
      inhibition of PKC activity and competition with a putative binding site.

PMID- 8257440
TI  - Structure of the glycosyl-phosphatidylinositol membrane anchor of
      acetylcholinesterase from the electric organ of the electric-fish, Torpedo
      californica.
AB  - The structure of the glycan moiety of the glycosyl-phosphatidylinositol (GPI)
      membrane anchor from Torpedo californica (electric fish) electric-organ
      acetylcholinesterase was solved using n.m.r., methylation analysis and chemical
      and enzymic micro-sequencing. Two structures were found to be present: Glc alpha
      1-2Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN alpha 1-6myo-inositol and Glc
      alpha 1-2Man alpha 1-2Man alpha 1-6(GalNAc beta 1-4)Man alpha 1-4GlcN alpha 1
      6myo-inositol. The presence of glucose in this GPI anchor structure is a novel
      feature. The anchor was also shown to contain 2.3 residues of ethanolamine per
      molecule.

PMID- 8257441
TI  - Activation of phosphatidylinositol 4,5-bisphosphate supply by agonists and non
      hydrolysable GTP analogues.
AB  - PtdIns(4,5)P2 serves as a precursor of a diverse family of signalling molecules,
      including diacylglycerol (and hence phosphatidic acid), Ins(1,4,5)P3 [and hence
      Ins(1,3,4,5)P4] and PtdIns(3,4,5)P3. The production of these messengers can be
      activated by agonists, and therefore the rate of utilization of PtdIns(4,5)P2 can
      vary dramatically. Although cells can only meet these large changes in demand for
      PtdIns(4,5)P2 by increasing its synthesis and/or by continuously cycling it at a
      rate that exceeds its potential consumption (avoiding the need for a co-ordinated
      activation mechanism), no satisfactory explanation for how this is achieved in
      agonist-stimulated cells has yet been provided. We show here that, in
      streptolysin-O-permeabilized neutrophils, N-formylmethionyl-leucyl-phenylalanine
      (FMLP), platelet-activating factor (PAF) and non-hydrolysable GTP analogues can
      cause large activations of PtdIns4P 5-kinase, suggesting that cells can
      accommodate agonist-activated rates of consumption of PtdIns(4,5)P2 without
      having to sustain continuous, comparably rapid and energetically expensive
      'futile cycling' reactions.

PMID- 8257442
TI  - Chemistry of collagen cross-links: glucose-mediated covalent cross-linking of
      type-IV collagen in lens capsules.
AB  - The incubation of lens capsules with glucose in vitro resulted in changes in the
      mechanical and thermal properties of type-IV collagen consistent with increased
      cross-linking. Differential scanning calorimetry (d.s.c.) of fresh lens capsules
      showed two major peaks at melting temperatures Tm 1 and Tm 2 at approx. 54
      degrees C and 90 degrees C, which can be attributed to the denaturation of the
      triple helix and 7S domains respectively. Glycosylation of lens capsules in vitro
      for 24 weeks caused an increase in Tm 1 from 54 degrees C to 61 degrees C, while
      non-glycosylated, control incubated capsules increased to a Tm 1 of 57 degrees C.
      The higher temperature required to denature the type-IV collagen after incubation
      in vitro suggested increased intermolecular cross-linking. Glycosylated lens
      capsules were more brittle than fresh samples, breaking at a maximum strain of
      36.8 +/- 1.8% compared with 75.6 +/- 6.3% for the fresh samples. The stress at
      maximum strain (or 'strength') was dramatically reduced from 12.0 to 4.7 N.mm.mg
      1 after glycosylation in vitro. The increased constraints within the system
      leading to loss of strength and increased brittleness suggested not only the
      presence of more cross-links but a difference in the location of these cross
      links compared with the natural lysyl-aldehyde-derived cross-links. The chemical
      nature of the fluorescent glucose-derived cross-link following glycosylation was
      determined as pentosidine, at a concentration of 1 pentosidine molecule per 600
      collagen molecules after 24 weeks incubation. Pentosidine was also determined in
      the lens capsules obtained from uncontrolled diabetics at a level of about 1 per
      100 collagen molecules. The concentration of these pentosidine cross-links is far
      too small to account for the observed changes in the thermal and mechanical
      properties following incubation in vitro, clearly indicating that another as yet
      undefined, but apparently more important cross-linking mechanism mediated by
      glucose is taking place.

PMID- 8257443
TI  - Specific inhibition of the activity of the urokinase receptor-mediated cell
      surface plasminogen activation system by suramin.
AB  - Urokinase-type plasminogen activator (uPA) is involved in generating the
      proteolytic activity necessary for invasive processes, and is dependent on
      binding to its specific cellular receptor (uPAR) for efficient function. We
      report here that the polysulphonated napthylurea compound suramin inhibits the
      activity of this cell-associated proteolytic system, in a manner independent of
      its antagonism of the uPA-uPAR interaction [Behrendt, Ronne and Dano (1993) J.
      Biol. Chem. 268, 5985-5989], occurring at a 25-100-fold-lower suramin
      concentration. This inhibition was found to be due to effects on the activation
      of both pro-uPA and plasminogen. Suramin inhibited plasmin activation of pro-uPA
      by a non-competitive mechanism (Ki approx. 2 micrograms/ml), which did not
      involve a direct effect on plasmin catalytic activity. Similarly, its effect on
      plasminogen activation was not due to a direct inhibition of uPA. The inhibition
      of plasminogen activation, which occurred exclusively with receptor-bound uPA,
      appeared to be due to a reversal of the favourable kinetics which result from the
      activation of cell-associated plasminogen, although suramin did not inhibit the
      cellular binding of 125I-labelled plasminogen. This suggests that this effect is
      due to interference with interactions between components of this system on the
      cell surface, and that suramin may be useful in gaining further insight into the
      molecular mechanisms involved in the functional assembly of this proteolytic
      system. Furthermore the effective inhibition of this system by suramin indicates
      an anti-invasive potential that may contribute to the anti-tumour effect of
      suramin in vivo.

PMID- 8257444
TI  - Reconstitution of the folding pathway of collagen in a cell-free system:
      formation of correctly aligned and hydroxylated triple helices.
AB  - We describe here a cell-free system which will carry out the initial stages in
      the synthesis, post-translational modification and assembly of type-X collagen.
      The mRNA coding for bovine type-X collagen was synthesized in vitro and
      translated in a rabbit reticulocyte lysate to yield a protein that was
      collagenase sensitive and could be immunoprecipitated with antibodies raised to
      purified avian type-X collagen. When type-X collagen was synthesized in the
      absence of added microsomes or in the presence of canine pancreas microsomes, the
      translation products showed partial resistance to digestion with pepsin but were
      completely degraded with a mixture of chymotrypsin and trypsin, suggesting that
      only incorrectly aligned non-native collagen molecules were synthesized under
      these conditions. When the protein was synthesized in the presence of microsomes
      derived from avian fibroblasts or a human fibrosarcoma cell line, the
      translocated product migrated as a diffuse band characteristic of hydroxylated
      collagen. The synthesized polypeptides were also resistant to both pepsin and
      trypsin/chymotrypsin digestion, demonstrating the formation of correctly aligned
      native collagen. Furthermore, the collagen polypeptides assembled into higher
      order structures, possibly trimers, which were stabilized by interchain
      disulphide bonds. The collagen helix synthesized in vitro had a melting
      temperature of 41 degrees C which is comparable with the protein synthesized in
      vivo, further demonstrating that the polypeptides were hydroxylated and that the
      triple helix formed was correctly aligned.

PMID- 8257445
TI  - Homology between neurohypophyseal hormone receptors.

PMID- 8257446
TI  - Early extracoronary atherosclerosis and coronary heart disease risk factors in a
      sample of civil servants in southern Italy.
AB  - One hundred and thirty-eight male subjects working as civil servants in the
      Catanzaro city hall, aged over 45, underwent Echo-Doppler examination of carotid
      and femoral arteries. Forty-one subjects (30%) presented evidence of early
      atherosclerotic lesions in at least 1 of the 10 examined arteries. Age, systolic
      blood pressure, serum triglycerides and serum glucose were higher in this group
      when compared with subjects without evidence of extracoronary atherosclerosis
      (EA), while HDL cholesterol and apolipoprotein A-I were lower. After adjustment
      for age, only serum triglycerides and apolipoprotein A-I levels remained
      significantly different. Only 21 subjects had no major coronary heart disease
      (CHD) risk factors, 46 had one, 47 two and 24 more than two risk factors. The
      prevalence of lesions was significantly higher in individuals with total
      cholesterol/HDL cholesterol ratio greater than 5. The presence of smoking and
      hypertension was almost equally represented in individuals with or without
      lesions. Serum triglycerides, total cholesterol/HDL cholesterol > 5 and
      apolipoprotein A-I seem to play a fundamental role in the development of EA, as
      detected by Duplex examination of carotid and femoral arteries. Age is also
      closely related to the presence of lesions, probably reflecting the exposure
      duration to CHD risk factors.

PMID- 8257448
TI  - Elevations in total plasma homocysteine in premature coronary artery,
      cerebrovascular and peripheral vascular disease.

PMID- 8257447
TI  - Effects of pravastatin on apolipoprotein-specific high density lipoprotein
      subpopulations and low density lipoprotein subclass phenotypes in patients with
      primary hypercholesterolemia.
AB  - The HMG-CoA reductase inhibitor class of cholesterol-lowering agents reduces very
      low density lipoproteins (VLDL) and low density lipoproteins (LDL) and slightly
      increases high density lipoproteins (HDL). However, the effects of these agents
      on subclasses within the LDL and HDL fractions are not well understood. We have
      employed an HMG-CoA reductase inhibitor, pravastatin, to determine if LDL
      subclass phenotypes, as determined by gradient gel electrophoresis, and HDL
      particles containing both apolipoprotein (apo) A-I and A-II, Lp(AI w AII), and
      those containing apo A-I but not A-II, Lp(AI w/o AII) are affected by pravastatin
      (10 mg daily). Twenty-four subjects with LDL-cholesterol (LDL-C) > 160 mg/dl,
      triglyceride (TG) < 350 mg/dl and no recent myocardial infarction or secondary
      causes of hypercholesterolemia were enrolled. Compared with an age- and sex
      matched normolipidemic reference group (controls), the hypercholesterolemic
      subjects had reduced levels of Lp(AI w/o AII) and increased levels of Lp(AI w
      AII) at baseline. In addition, both of their HDL subpopulations had significantly
      more small (7.0-8.2 nm) particles (P < 0.02 and 0.0001) but significantly fewer
      large (9.2-11.2 nm) particles (P < 0.002 and 0.0001). Pravastatin induced
      statistically significant (P < 0.001) reductions in plasma total C (15%), LDL-C
      (18%), and apo B (16%). While apo A-I and A-II levels increased 5% (P < 0.001)
      and 6% (P < 0.05), respectively, concentration, composition, and size
      abnormalities in Lp(AI w AII) and Lp(AI w/o AII) persisted. Lp(a), apo E and
      cholesteryl ester transfer protein (CETP) levels also did not change. Although
      changes in LDL subclass phenotypes were observed, all changes involved the
      intermediate phenotype, and no significant changes in LDL peak particle diameter
      were seen in either group. Interrelationships between CETP, LDL subclass
      phenotypes and HDL subpopulations were also seen. CONCLUSIONS: Although
      pravastatin decreased plasma apo B and LDL lipid concentrations, no major changes
      were seen in LDL subclass phenotypes or HDL subpopulations even in the presence
      of abnormalities associated with arteriosclerosis. Similarly, CETP, which is
      believed to play a role in HDL and LDL particle size distribution, did not change
      with pravastatin treatment. Further research is needed to determine the
      pathophysiological basis of abnormal HDL and LDL subclasses in
      hypercholesterolemia and explore methods of rectifying the abnormalities.

PMID- 8257449
TI  - In memoriam David H. Blankenhorn, M.D. 1924-1993.

PMID- 8257450
TI  - Effect of hyperapo B LDL on cholesterol esterification in THP-1 macrophages.
AB  - Hyperapobetalipoproteinemia (hyperapo B), a common disorder associated with
      coronary artery disease, is characterized by an increased number of small, dense,
      low density lipoprotein (LDL) particles. The cellular mechanisms responsible for
      early atherosclerosis in hyperapo B are unknown. We tested the hypothesis that
      hyperapo B LDL may be preferentially metabolized through an LDL receptor
      independent pathway promoting the accumulation of cellular cholesteryl ester
      (CE). THP-1 macrophages have little inducible LDL receptor activity after
      differentiation with phorbol esters and are, therefore, suitable for assessing
      non-LDL receptor mediated uptake of lipoproteins. LDL isolated from hyperapo B
      donors was found to have significantly lower total cholesterol to protein ratio
      (P = 0.03), higher average density (P = 0.0001) and smaller particle diameter (P
      = 0.016) compared with normal (control) LDL. LDL (250 micrograms lipoprotein
      protein/ml) from normal (n = 11) and hyperapo B (n = 18) subjects were incubated
      for 24 h with THP-1 macrophages. The mean (S.D.) CE accumulation was 6.2 (3.6)
      for the normal and 6.4 (2.6) for the hyperapo B LDL (P = 0.84). CE accumulation
      in cells incubated with malondialdehyde modified (MDA) LDL, or without added
      lipoprotein, was 18.2 (2.0) and 0.6 (0.7), respectively. CE mass accumulation was
      significantly correlated with time (6-48 h) of incubation and concentration (100
      500 micrograms/ml) of LDL protein (P < 0.05); no differences were observed
      between normal and hyperapo B LDL. Similarly, when the major LDL species was
      isolated by density gradient ultracentrifugation, mean (S.D.) CE was similar for
      the normal and hyperapo B LDL (8.7 (1.2) vs. 6.9 (1.5)). There were no
      differences in the mean (S.D.) incorporation of [14C]oleate into CE (nmol/mg cell
      protein per 6 h) in THP-1 macrophages incubated with normal or hyperapo B LDL
      (0.238 (0.045) vs. 0.211 (0.046)); results were comparable in human monocyte
      derived (HMD) macrophages (0.298 (0.037) vs. 0.258 (0.022)). Also, mean (S.D.)
      cellular uptake and degradation (ng 125I/mg cell protein per h) in THP
      macrophages of normal and hyperapo B LDL were similar (uptake: 18 (14) vs. 12
      (6.0); degradation: 58 (32) vs. 44 (8)). In summary: (1) hyperapo B LDL did not
      stimulate the accumulation of cellular CE via LDL receptor independent pathways
      in THP-1 macrophages, (2) normal and hyperapo B LDL stimulation of CE synthesis
      is similar in THP-1 and HMD macrophages and (3) no differences in cellular uptake
      and degradation of normal and hyperapo B LDL were observed in THP macrophages.

PMID- 8257451
TI  - Effect of coarctation on matrix content of experimental aortic atherosclerosis:
      relation to location, plaque size and blood pressure.
AB  - Cynomolgus monkeys were fed an atherogenic diet for 6 months following surgically
      produced high-grade (n = 10) or mild (n = 16) mid-thoracic aortic coarctation. A
      diet-control (DC) group (n = 13) was fed the diet without coarctation. High-grade
      coarctation (HGC) resulted in 74.1% +/- 8.3% stenosis by aortography prior to
      sacrifice and was associated with systolic brachial blood pressures of 143.3 +/-
      26.0 mmHg and gradients across the stenoses of 36.8 +/- 23.6 mmHg. Mild
      coarctation (MC) resulted in stenoses of 50.9% +/- 12.9%, brachial systolic
      pressures of 119.4 +/- 25.7 and gradients of 12.5 +/- 15.2 mm Hg (P < 0.01, P =
      0.03 and P < 0.005, respectively, compared with HGC). When total plaque cross
      sectional area exceeded 0.8 mm2, the entire arterial circumference was usually
      involved. HGC resulted in complete sparing or minimal plaque formation in
      sections distal to the stenoses compared with proximal sections (P < 0.001).
      There were no significant differences between MC and DC animals in plaque
      location or size. Matrix content increased with plaque area regardless of degree
      of stenosis or sampling level (P < 0.01), but lesions with more than 75% matrix
      content were more numerous in distal than in proximal sections despite their
      smaller size. The number of plaques with greater than 75% matrix content was
      increased proximal to HGC (P < 0.04). Thus, distal location and plaque size were
      independent determinants of plaque matrix content and matrix content was
      increased proximal to HGC regardless of plaque size. Attempts to evaluate effects
      of various regimens and interventions on plaque composition need to take location
      and plaque size, as well as blood pressure differences, into account.

PMID- 8257452
TI  - The binding of very low density lipoprotein remnants to the low density
      lipoprotein receptor in familial defective apolipoprotein B-100.
AB  - We have compared the affinity for low density lipoprotein (LDL) receptors of LDL
      and very low density lipoprotein (VLDL) remnants from patients with familial
      defective apo B-100 (FDB) with that of LDL and VLDL remnants from normal
      subjects. The binding affinity of FDB LDL was markedly reduced in all 14 FDB
      patients examined, hut the affinity of FDB remnants did not differ significantly
      from that of remnants prepared from normal subjects. Since the mutant form of apo
      B-100 present in FDB is recognized by LDL receptors with greatly reduced
      efficiency, we suggest that apo B plays only a minor role in the receptor
      mediated uptake of VLDL remnants by the liver in man. These results are
      consistent with our previous suggestion that the ability of drugs that stimulate
      hepatic receptor activity to lower the plasma LDL level in FDB is due in part to
      increased hepatic uptake of lipoprotein precursors of LDL, including remnant
      particles with normal apo B-100 and those with mutant apo B-100.

PMID- 8257453
TI  - Glycosylated low density lipoprotein is more sensitive to oxidation: implications
      for the diabetic patient?
AB  - Oxidised low density lipoprotein (LDL) is considered to be atherogenic. This
      study examined the relationship between glycosylation and oxidation of LDL from
      10 normocholesterolaemic Type 2 diabetic patients, 10 hypercholesterolaemic Type
      2 diabetic patients, and 10 normocholesterolaemic non-diabetic subjects. LDL was
      isolated by sequential ultracentrifugation and susceptibility to oxidation
      assessed by measuring thiobarbituric reactive substances (TBARS) during a 4-h
      oxidation period. LDL glycosylation was measured by aminophenylborate gel
      chromatography. Results demonstrated an increased susceptibility to oxidation in
      LDL from both diabetic groups, the mean 3-h TBARS values being 35.2 +/- 2.1 and
      36.4 +/- 2.6 nmol MDA/mg LDL protein for normocholesterolaemic and
      hypercholesterolaemic diabetic patients compared with 24.5 +/- 2.5 nmol MDA/mg
      LDL protein for control subjects. LDL glycosylation of 2.20% +/- 0.11% and 2.89%
      +/- 0.46% for normocholesterolaemic and hypercholesterolaemic diabetic LDL was
      significantly higher than that for the non-diabetic control subjects of 1.60% +/-
      0.12% (P < 0.02). There was a significant positive correlation (P < 0.005)
      between LDL glycosylation and LDL oxidation. The esterified/free cholesterol
      ratio which correlated positively with oxidation (P < 0.01) was significantly
      higher in LDL from both diabetic groups compared with LDL from control subjects
      (P < 0.01). Thus the increased incidence of atherosclerosis in diabetes may be
      related to glycosylation of LDL through its increased susceptibility to
      oxidation.

PMID- 8257454
TI  - Indications for the presence of circulating peroxidized low density lipoproteins
      in WHHL rabbits treated with antioxidants.
AB  - Low density apolipoprotein (apo) B-100 in homozygous WHHL rabbits appears
      heterogeneous on SDS-PAGE. At least four high molecular weight apolipoproteins
      were identified in contrast to the uniform apo B-100 band in the very low density
      lipoprotein (VLDL) fraction of WHHL-homozygotes and the apo B containing
      lipoproteins present in WHHL heterozygotes or New Zealand White rabbits. We
      studied whether these aberrations in homozygote WHHL-LDL were due to physical
      changes induced by lipid peroxidation. Therefore we treated WHHL rabbits for 28
      days with a standard dose of 1% probucol or with a dose of 0.1% vitamin E and
      studied the parameters indicating lipid peroxidation in circulating LDL and in
      vitro in relation to its antioxidant content. The LDL of probucol-fed rabbits
      appeared completely resistant against oxidation in vitro with Cu2+ ions. LDL
      fluorescence and serum malondialdehyde concentrations, indicators of lipid
      peroxidized LDL, were lower than in the control WHHL rabbits. LDL of vitamin E
      fed WHHL rabbits showed a twofold increased lag phase in comparison with LDL of
      control-fed animals; the maximal rate of oxidation was 2- to 3-fold lower while
      LDL fluorescence was between the values obtained in the two other groups.
      Malondialdehyde concentration in the vitamin E-treated group was also decreased
      when compared with controls. Despite these indications of increased lipid
      peroxidized circulating LDL in WHHL controls which could be reversed, at least
      partially, by the antioxidant treatments applied, these treatments were without
      effect on the physical structure of LDL as examined with agarose gel
      electrophoresis. Neither antioxidant treatment changed the typical apo B-100
      pattern in WHHL-LDL.

PMID- 8257455
TI  - Effect of gemfibrozil on high density lipoprotein subspecies in non-insulin
      dependent diabetes mellitus. Relations to lipolytic enzymes and to the
      cholesteryl ester transfer protein activity.
AB  - Twenty patients (18 men, 2 women) with non-insulin dependent diabetes mellitus
      (NIDDM) were randomized to receive either gemfibrozil 1200 mg daily or placebo
      for 3 months in a double-blind study. The effect of gemfibrozil on plasma HDL
      subfraction distribution was studied with sequential and density gradient
      ultracentrifugation and in gradient gel electrophoresis. The concentrations of
      apo A-I, apo A-II, Lp A-I and Lp A-I:A-II particles were measured. Postheparin
      plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and plasma
      cholesteryl ester transfer protein (CETP) activities were also determined.
      Gemfibrozil increased the concentration of HDL cholesterol (P < 0.01), which was
      due to the rise of HDL3 cholesterol (+16%), while in the placebo group these
      values remained unchanged. Gemfibrozil increased the concentrations of apo A
      I(+12.6%, NS), apo A-II (+28.2%, P < 0.01) and Lp A-I:A-II particles (+21.6%, P <
      0.06) but there were no changes in the placebo group. Neither gemfibrozil nor
      placebo had any effect on the concentration of Lp A-I particles. As determined by
      density-gradient ultracentrifugation, gemfibrozil increased the concentration of
      cholesterol in the most dense HDL fractions (mean density 1.193 g/ml, +22%, P <
      0.05 and mean density 1.158 g/ml, +19.3%, P < 0.05). In gradient gel
      electrophoresis, the gemfibrozil-induced elevations of the cholesterol and
      protein were most pronounced in the HDL3a (8.8-8.2 nm) region. Gemfibrozil
      increased LPL and HL activities by 14.7% (P < 0.05) and by 18.8% (P < 0.01),
      respectively, while in the placebo group LPL and HL activities remained
      unchanged. Plasma CETP activity was also increased during gemfibrozil treatment
      while in the placebo group it remained unchanged. We conclude that gemfibrozil
      causes multiple changes in plasma HDL metabolism. The gemfibrozil-induced
      elevation of HDL3 and dense HDL subpopulations may reflect the concerted action
      of LPL, HL and CETP on plasma HDL metabolism.

PMID- 8257456
TI  - The relationship between the degree of dietary-induced hypercholesterolemia in
      the rabbit and atherosclerotic lesion formation.
AB  - A biochemical, histologic and morphometric evaluation of spontaneous, diet
      induced (thoracic aorta) and injury-induced (iliac-femoral) atherosclerotic
      lesions was performed in rabbits maintained on varying levels of dietary
      cholesterol. Rabbits were meal-fed a 3% peanut oil, 3% coconut oil diet
      containing 0%, 0.1%, 0.25%, 0.5%, 1.0%, 1.5% or 2.0% cholesterol for 9 weeks.
      Plasma total cholesterol exposure (area under cholesterol-time curve (TC-AUC))
      increased diet-dependently over the course of the study. VLDL and LDL cholesterol
      (VLDL-C, LDL-C) comprised 41% and 55%, respectively, of the plasma total
      cholesterol at cholesterol levels > 700 mg/dl (TC-AUC > 31,868 mg day/dl) and
      both VLDL-C and LDL-C were linearly related to TC-AUC (r = 0.98). Plasma TC-AUC
      was linearly related to thoracic aortic cholesteryl ester (CE) content (r = 0.74)
      and thoracic aortic lesion coverage (r = 0.66). In the injury-induced iliac
      femoral lesion, plasma TC-AUC was linearly related to both iliac-femoral CE
      content (r = 0.80) and macrophage/lesion ratio (r = 0.64). At plasma cholesterol
      levels greater than 700 mg/dl, CE content of the iliac-femoral lesion ranged from
      35 to 69 micrograms/mg dry defatted tissue, > 75% of the lesions were fibrofoamy
      in nature and macrophage/lesion area ratio was 0.46 to 0.55 while lesion area
      remained constant. VLDL-C and LDL-C were highly correlated with the CE content of
      both thoracic and iliac-femoral lesions, thoracic aortic lesion coverage and
      macrophage/lesion area ratio (r = 0.86-0.99). We conclude that the composition,
      extent and type of atherosclerotic lesion induced in rabbits is dependent upon
      the overall plasma cholesterol exposure, VLDL and LDL cholesterol content and
      whether lesions are induced by diet alone or both diet and chronic endothelial
      injury. In addition, various stages of atherosclerotic lesion formation can be
      replicated in the rabbit by titrating the animal's overall plasma cholesterol
      exposure.

PMID- 8257457
TI  - Thromboxane production in the blood of women increases after menopause whereas
      tumor necrosis factor is reduced in women compared with men.
AB  - Previously we have shown that incubation of heparinized blood with a low dose of
      lipopolysaccharides (5 ng/ml) resulted in a 60% higher generation of TxB2 in the
      blood of young men as compared with that of young women. In the present study, we
      investigated a group consisting of 38 healthy men and 38 healthy postmenopausal
      women aged 50-73 years with no drug use and no known chronic disease. In contrast
      to our earlier observation that young men produce more TxB2 than young women, no
      significant difference was observed between the men and women when all the
      participants above 50 years of age were included (5.7 +/- 0.6 ng/l for men versus
      5.2 +/- 0.7 ng/l for women). However, a strong correlation was found with simple
      regression analysis when increasing TxB2 generation was compared with years after
      menopause (P < 0.0001). No such correlation was observed for increasing age of
      men and their TxB2 production. The LPS stimulation system of whole blood was also
      used to evaluate the production of tumor necrosis factor (TNF-alpha) in older
      people. Men were found to generate 60% more TNF-alpha than women, but no
      correlation was found between increasing age of women and TNF-alpha production as
      observed with TxB2. Risk factors such as SDS-cholesterol, fibrinogen and factor
      VII were the same in men and women, whereas total cholesterol was higher in women
      than in men (P < 0.05). Since TxA2 is known to be a mediator of atherosclerotic
      induced lesions and TNF-alpha is a well-established indicator of inflammatory
      reactions, we propose that the reduced production of TxB2 and TNF-alpha in women
      in our model system may partially explain the lower incidence of atherosclerosis
      in women as compared with men, and the phenomenon of increased incidence of this
      disease after menopause.

PMID- 8257458
TI  - Carotid intima-media wall thickness in elderly women with and without
      atherosclerosis of the abdominal aorta.
AB  - In the present study the association was evaluated between non-invasively
      assessed atherosclerosis of the abdominal aorta and ultrasonographically measured
      intima-media wall thickness of the common carotid arteries in a population-based
      study of 41 elderly women. Atherosclerosis of the abdominal aorta was assessed in
      1985 using a lateral X-ray of the lumbar spine, on which the presence of
      calcified deposits was determined. The carotid arteries were ultrasonographically
      evaluated in 1990 for presence of atherosclerotic plaques and intima-media wall
      thickness of the distal common carotid was measured off line using dedicated
      software. The age-adjusted mean intima-media wall thickness of the right common
      carotid artery was significantly higher in subjects with calcified deposits in
      the aorta (n = 16) compared with those without deposits (n = 25) with a mean
      difference of 0.15 mm (95% confidence interval (CI) 0.03, 0.26). For the left
      side similar results were observed. Mean common carotid intima-media wall
      thickness, ((left+right)/2), differed significantly across groups with a mean
      difference of 0.11 mm (95% CI 0.01, 021). Additional adjustment for differences
      across groups in body mass index, serum cholesterol, hypertension and smoking did
      not change the magnitude of the observed association: mean difference of 0.12 mm
      (95% CI -0.01, 0.25). The findings of the present study provide evidence that
      among subjects with atherosclerotic plaques in the abdominal aorta, the intima
      media wall thickness of the distal common carotid arteries is increased.

PMID- 8257459
TI  - Controlling costs by "managed competition"--would it work?

PMID- 8257460
TI  - Surgical repair of an anterior tibialis muscle hernia with Mersilene mesh.
AB  - The most frequent muscle hernia of the lower extremities is the anterior tibialis
      muscle hernia. A number of surgical procedures are available for the treatment of
      symptomatic anterior tibialis muscle hernias. However, in case of a large fascial
      defect, their use may be unfeasible or inconvenient. Moreover, current surgical
      procedures are prone to the risk of an anterior tibial compartment syndrome. The
      use of a synthetic patch could provide an alternative, particularly for large
      defects. In this paper we report the repair of a large, symptomatic, long
      standing anterior tibialis muscle hernia with polyester mesh (Mersilene) fixed to
      the edges of the defect (muscular fascia and tibial periosteum). This simple
      procedure provided excellent functional results and a good cosmetic appearance
      without complications and sequelae.

PMID- 8257461
TI  - Sliding toward nutrition malpractice: time to reconsider and redeploy.

PMID- 8257462
TI  - The central nervous system serotonin syndrome.

PMID- 8257463
TI  - A new approach to prenatal cystic fibrosis carrier screening.

PMID- 8257464
TI  - Gastrointestinal motility disorders during pregnancy.
AB  - PURPOSE: To review the pathophysiology of gastrointestinal motility disorders
      during pregnancy, their clinical manifestations, and their management. DATA
      SOURCES: Studies published from 1963 to 1992 identified by computerized
      literature searches of Index Medicus and MEDLINE; hand searches; contact with
      pharmaceutical representatives for information on drug therapy during pregnancy;
      and selected texts on drugs and obstetrics. STUDY SELECTION: Selected studies
      were those involving controlled design of physiology related to pregnancy or to
      hormonal effects on the gastrointestinal tract or both, and clinical studies or
      previous reviews that contributed to the understanding of the gastrointestinal
      effects of pregnancy. DATA EXTRACTION: Data concerning the epidemiology, causes,
      clinical manifestations, and complications of altered gastrointestinal motility
      during pregnancy as well as the strength of association between gastrointestinal
      disorders of pregnancy and hormonal changes were evaluated and used to develop a
      practical approach to evaluate and manage these patients. RESULTS OF DATA
      SYNTHESIS: Effects on the gastrointestinal tract during pregnancy are caused
      primarily by hormonal changes and not the physical effects of the gravid uterus.
      Motility changes occur throughout the gastrointestinal tract, including a
      reduction in lower esophageal sphincter pressure and its physiologic function
      with resulting gastroesophageal reflux and the risk for aspiration; alterations
      in gastric motor function associated with nausea and vomiting; and a decrease in
      the rate of small-bowel and colonic transit manifested primarily as abdominal
      bloating and constipation. These effects are mediated by progesterone, with
      estrogen probably acting as a primer. CONCLUSIONS: Given the large number of
      pregnancies each year complicated by gastrointestinal motility disorders, many
      physicians (including internists and gastroenterologists) must manage these
      problems. Knowledge of the underlying physiologic alterations in gastrointestinal
      motility during pregnancy and of safe treatment options is essential to the care
      of the pregnant patient.

PMID- 8257465
TI  - Rapidly progressive aphasic dementia and motor neuron disease.
AB  - Articulatory and language impairment heralded rapidly progressive motor neuron
      disease in 7 patients aged 54 to 77 years. One patient had a family history of a
      similar disorder. Severe nonfluent aphasia developed in all 7 patients and 4 were
      anarthric within a year. Other cognitive domains were impaired, yet 2 patients
      lived alone until 1 month before their deaths. Four died within 2 years.
      Abnormalities were found on electromyography, computed tomography, magnetic
      resonance imaging, single-photon emission computed tomography, and
      electroencephalography. Neuropathological examination in 3 patients showed
      bilateral hemispheric atrophy with neuronal loss and gliosis predominantly of
      superficial cortical layers. Pigmented and hypoglossal nuclei were relatively
      preserved. At all spinal levels there was degeneration of corticospinal tracts
      and loss of anterior horn cells with gliosis. Rapidly progressive aphasic
      dementia and motor neuron disease are a distinctive clinical entity whose
      nosology is poorly understood.

PMID- 8257466
TI  - Percutaneous tracheostomy.
AB  - Elective tracheostomy is commonly performed on patients in intensive care units
      who require assisted ventilation for more than 1-2 weeks. Percutaneous
      dilatational techniques have recently been developed which allow tracheostomies
      to be performed at the bedside. These compare favourably with conventional
      techniques.

PMID- 8257467
TI  - The therapeutic alliance and the psychiatric emergency room.

PMID- 8257468
TI  - Cold preservation of enteric free flaps: an experimental study.
AB  - Enteric free flaps have proven to be useful in the reconstruction of the
      esophagus. This study was designed to determine whether cold preservation can
      prolong the ischemia time of enteric flaps from the distal small bowel. Adult
      mongrel dogs were anesthetized, and the abdomen was opened at the midline. Two 10
      cm portions of the distal small bowel were identified and dissected out on a
      single pedicle. The bowel was then divided, and one segment was cooled with iced
      saline sponges while the second segment was not. The blood supply to both
      segments was then clamped. After 2 hours, the bowel was reanastomosed, and the
      cold segment was marked. Twenty-four hours later, the dogs were reanesthetized
      and given fluorescein and the bowel was then examined under the Woods lamp.
      Sections from both the warm ischemia and cold ischemia bowel were examined
      histologically. Results indicated that cooling the bowel can retard histologic
      changes that ischemia produces in the bowel.

PMID- 8257469
TI  - Ancestors may provide clinical answers, say 'Darwinian' medical evolutionists.

PMID- 8257470
TI  - Effect of problem-based, self-directed undergraduate education on life-long
      learning.
AB  - OBJECTIVE: To compare how well graduates of a self-directed, problem-based
      undergraduate curriculum (at McMaster University [MU], Hamilton, Ont.) and those
      of a traditional curriculum (at the University of Toronto [UT]) who go on to
      primary care careers keep up to date with current clinical practice guidelines.
      DESIGN: Analytic survey. Management of hypertension was chosen as an appropriate
      topic to assess guideline adherence. An updated version of a previously validated
      questionnaire was mailed to the participants for self-completion. SETTING:
      Private primary care practices in southern Ontario. PARTICIPANTS: A random sample
      of 48 MU graduates and 48 UT graduates, stratified for year of graduation (1974
      to 1985) and sex, who were in family or general practice in Ontario; 87% of the
      eligible subjects in each group responded. MAIN OUTCOME MEASURES: Overall and
      component-specific scores; analysis was blind to study group. RESULTS: The
      overall mean scores were 56 (68%) of a possible 82 for the MU graduates and 51
      (62%) for the UT graduates (difference between the means 5, 95% confidence
      interval 1.9 to 8.2; p < 0.01). Multivariate linear regression analysis of seven
      factors that might affect questionnaire scores revealed that only the medical
      school was statistically significant (p < 0.01). The MU graduates had
      significantly higher mean scores than the UT graduates for two components of the
      questionnaire: knowledge of recommended blood pressures for treatment (p < 0.05)
      and successful approaches to enhance compliance (p < 0.005). The trends were
      similar for the other components but but were not significant. CONCLUSIONS: The
      graduates of a problem-based, self-directed undergraduate curriculum are more up
      to date in knowledge of the management of hypertension than graduates of a
      traditional curriculum.

PMID- 8257471
TI  - Administration of metered dose inhalers during anesthesia via CO2 monitor port.

PMID- 8257472
TI  - Effect of early amniotomy on the risk of dystocia in nulliparous women. The
      Canadian Early Amniotomy Study Group.
AB  - BACKGROUND: Early amniotomy has been advocated as a means of preventing dystocia,
      but its efficacy has not been studied prospectively. The purpose of this
      multicenter study was to determine whether routine early amniotomy reduces the
      risk of dystocia for nulliparous women in spontaneous labor. METHODS: We studied
      925 nulliparous women in labor, who were stratified according to the degree of
      cervical dilatation (< 3 cm vs. > or = 3 cm) and randomly assigned to either
      early rupture of the membranes (amniotomy group) or conservative management of
      labor (conservative-management group). Dystocia was defined as a period of at
      least four hours after dilatation of the cervix to 3 cm had been reached during
      which the mean rate of cervical dilatation was less than 0.5 cm per hour.
      RESULTS: Dystocia was significantly less frequent in the amniotomy group than in
      the conservative-management group (34 percent vs. 45 percent; relative risk, 0.8;
      95 percent confidence interval, 0.6 to 0.9). The median length of time from
      randomization to full dilatation was 136 minutes shorter in the amniotomy group,
      and there was a trend toward less frequent use of oxytocin among the women
      assigned to amniotomy (36 percent vs. 41 percent; relative risk, 0.9; 95 percent
      confidence interval, 0.8 to 1.0). In a stratified analysis, the frequency of
      dystocia associated with amniotomy was reduced only among women with > or = 3 cm
      initial dilatation. The cesarean-section rate was similar in the two groups
      (amniotomy, 12 percent; conservative management, 11 percent). There were no
      statistically significant differences in outcome between the infants delivered by
      the women in the two groups; the measures of an adverse outcome included
      admission to a neonatal intensive care unit, five-minute Apgar score below 7, and
      arterial cord-blood pH below 7.2. CONCLUSIONS: Early amniotomy is an effective
      method of shortening the duration of labor and reducing the frequency of dystocia
      among nulliparous women in labor, but it does not lower the rate of cesarean
      section.

PMID- 8257473
TI  - An autopsy case of cerebellar degeneration following lithium intoxication with
      neuroleptic malignant syndrome.
AB  - We report a rare case of cerebellar degeneration that was diagnosed at autopsy in
      a patient who developed lithium intoxication accompanied by neuroleptic malignant
      syndrome. This 63 year old female, who suffered from manic depressive psychosis,
      had received lithium bicarbonate at a daily dose of about 1000 mg for 4 years.
      She developed a high fever and extrapyramidal symptoms resembling a neuroleptic
      type of malignant syndrome and died 1 month later. Autopsy revealed an almost
      complete loss of Purkinje cells with a mild reduction of granule cells in most
      areas of the cerebellar hemisphere and vermis, except for the tonsil and
      flocculus, and mild gliosis in the dentate nucleus. In cases of suspected lithium
      intoxication, one must be alert to the possibility of neuroleptic malignant
      syndrome and to prevent cerebellar degeneration.

PMID- 8257474
TI  - Lest we forget: our investment in animal research.

PMID- 8257475
TI  - Dietary fiber, inulin, and oligofructose: a review comparing their physiological
      effects.
AB  - Dietary fiber is a general term. It covers a wide variety of substances that
      belong to the family of carbohydrates that resist hydrolysis by human alimentary
      enzymes but are fermented by colonic microflora. The main physiological effects
      of dietary fiber are primarily on gastric emptying and small intestinal transit
      time, resulting in an improved glucose tolerance and a decreased digestion of
      starch: second, on colonic transit time and large bowel functions due to
      fermentation by ceco-colonic microbial flora or bulking action. The so-called
      soluble dietary fibers are fermented to a large extent by a wide variety of
      anaerobic bacteria that result in an increase in bacterial biomass, an increase
      in fecal mass, a change in intracolonic pH, and production of short chain fatty
      acids and various gases as metabolic end products. The insoluble fibers are only
      marginally fermented: they serve almost exclusively as bulking agents that result
      in shorter transit time and increased fecal mass. The short chain fatty acids
      resulting from the colonic fermentation of dietary fiber are largely absorbed via
      the portal blood and reach both the liver and the peripheral tissues. They induce
      changes in glucose and fat metabolism leading to post-prandial hypoglycemia and
      long-term hypolipidemia. Inulin and oligofructose are fructans with a degree of
      polymerization of 2 to 60 and 2 to 20, respectively. Due to the structural
      conformation of their osidic bridge (beta 2-1), they both resist the hydrolysis
      by human alimentary enzymes. Moreover, when reaching the colon, both inulin and
      oligofructose are almost quantitatively fermented almost exclusively by colonic
      bifidobacteria and bacteroides. Such an extensive fermentation causes an increase
      in fecal bacterial biomass, a decrease in ceco-colonic pH, and produces a large
      amount of fermentation products among which the short chain fatty acids that
      exert systemic effects on lipid metabolism. Thus, both inulin and oligofructose
      have most of the characteristics of a dietary fiber and the proposal is made to
      classify them as such. Moreover, they are bifidogenic factors, because, due to
      still unknown reasons, they are primarily fermented by bifidobacteria. It is
      concluded from this review that "nondigestible fructo-oligosaccharides," even
      though they are not included in the carbohydrate fraction that is quantified as
      dietary fiber by classic analytical methods, have most of the physiological
      effects of a dietary fiber.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8257476
TI  - Treatment of cancer patients with ex vivo anti-CD3-activated killer cells and
      interleukin-2.
AB  - PURPOSE: This study describes the physiologic and biologic effects resulting from
      the adoptive transfer of ex vivo anti-CD3-stimulated T-killer cells (T-AK) to
      patients with advanced cancer in combination with interleukin-2 (IL-2). METHODS:
      Autologous peripheral-blood mononuclear cells were obtained by leukapheresis and
      stimulated ex vivo with anti-CD3. The stimulated cells were reinfused at one of
      three dose levels on the next day (5 x 10(9), 7.5 x 10(9), and 1 x 10(10)). Cell
      administration was followed by IL-2 given by bolus and continuous infusion (1.5 x
      10(6) U/m2 and 3.0 x 10(6) U/m2, respectively) for 7 days, or continuous infusion
      alone (3.0 x 10(6) U/m2) for 14 days. RESULTS: Pronounced leukocytosis and
      atypical lymphocytosis were observed with individual values as high as 80,000 and
      50,000 cells/microL, respectively. The other major clinical sequelae included a
      marked lactic acidosis with bicarbonate levels as low as 4.0 mmol/L in some
      patients, and prolongation of the prothrombin time (PT) and partial
      thromboplastin time (PTT) due to decreases in clotting factors VII, IX, and X.
      Antithrombin III levels were also reduced. Hypotension associated with increased
      serum nitrate and neopterin levels was observed. These toxicities were
      accompanied by increases in hepatocellular enzymes and creatinine previously
      described with IL-2. These events occurred at a time when the number of
      circulating T-AK cells reached their peak. The amount of bolus IL-2 correlated
      with increases in WBC count (P = .0311), atypical lymphocytes (P = .0241), PT (P
      = .0006), and PTT (P = .0122). CONCLUSION: Substantial in vivo expansion of
      activated T lymphocytes was induced by a protocol combining ex vivo activation of
      peripheral-blood cells with anti-CD3 antibody followed by adoptive transfer and
      IL-2 administration. The synchronous expansion of these T cells superimposed on
      diminished liver and kidney function from IL-2 can cause profound but reversible
      metabolic changes.

PMID- 8257477
TI  - The use of qualitative research in the development of the "Heartwise" program for
      general practitioners.

PMID- 8257478
TI  - Oral 5'-methyltetrahydrofolic acid in senile organic mental disorders with
      depression: results of a double-blind multicenter study.
AB  - 5'-Methyltetrahydrofolic acid (5'-MTHF) in addition to standard psychotropic
      medication significantly improved clinical recovery in depressed patients with
      borderline or definite folate deficiency, and significantly reduced depressive
      symptoms in elderly normofolatemic patients after 3 weeks of treatment. In this
      equivalence study the effect of 5'-MTHF on depressive symptoms and cognitive
      status was compared to Trazodone (TRZ) in normofolatemic elderly patients with
      mild to moderate dementia and depression. Ninety-six patients with dementia,
      scoring 12-23 at the Mini Mental State Examination (MMSE) and > or = 18 at the
      Hamilton Depression Rating Scale (HDRS) after a 2-week placebo run-in, were
      randomized to receive either 5'-MTHF (50 mg/day p.o.) (47 patients) or TRZ (100
      mg/day p.o.) (49 patients) in a double-blind design for 8 weeks. HDRS was
      assessed before, after 4 weeks and at the end of treatment; Rey's Verbal Memory
      (RVM) test for immediate and delayed recall was evaluated before and after
      treatment. After 4 weeks of treatment HDRS score was reduced from 23 +/- 5 to 20
      +/- 6 in the 5'-MTHF (p < 0.05 vs baseline), and from 23 +/- 3 to 21 +/- 4 in the
      TRZ group (p < 0.05 vs baseline). A further significant decrease to 18 +/- 6 and
      19 +/- 5 respectively was obtained at the end of the treatment period (p < 0.05
      vs week 4) with 5'-MTHF and TRZ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257479
TI  - An epidemic outbreak of hepatitis E in Yangon of Myanmar: antibody assay and
      animal transmission of the virus.
AB  - An epidemic outbreak of hepatitis E occurred in an army recruit camp of Yangon,
      Myanmar, in October 1989. One hundred and eleven patients among 600 residents
      were hospitalized. As high as 83.7% of these patients were positive for the acute
      phase antibody against hepatitis E virus by an enzyme-linked immunosorbent assay
      developed in our laboratory. Also, 30.6% of 49 symptom-free residents examined
      were positive for the antibody. We prepared a stool extract from six patients and
      inoculated it into 10 rhesus monkeys for a series of three sub-passages. All of
      them developed acute biochemical hepatitis along with an elevation of antibody
      levels. A rechallenge with viruses of the present outbreak failed to provoke
      hepatitis in two monkeys that had previously recovered from acute hepatitis
      caused by an isolate of sporadic hepatitis E of the same area. Similarly, the
      rechallenge of the sporadic strain did not induce hepatitis in two monkeys that
      had been previously infected with the epidemic virus. These data suggested that
      the subjects would obtain neutralizing antibodies against the hepatitis E virus
      once infected, and many adult inhabitants of the endemic area had no protective
      antibodies and were still susceptible to hepatitis E infection.

PMID- 8257480
TI  - Criteria for valid preclinical trials using animal stroke models.

PMID- 8257481
TI  - The hospital--creating a pain-free environment: a program to improve pain control
      in hospitalized patients.

PMID- 8257482
TI  - Controlled studies of multivitamin supplementation on pregnancy outcomes.
AB  - The Hungarian Family Planning Program includes a randomized prospective blind
      study of periconceptional multivitamin and trace element supplementation to test
      the efficacy of this treatment in the reduction of the first occurrence of neural
      tube defect. This program is appropriate for the evaluation of pregnancy outcomes
      in general. Periconceptional multivitamin supplementation had no beneficial
      effect on fetal death, that is, chemical and ectopic pregnancies, missed
      miscarriages, miscarriages, and stillbirths. The proportion of low birth weight
      (5.8%) was higher in the combined vitamin I-II sample than in the combined trace
      element I-II sample (4.3%), but it was explained by a higher rate of multiple
      births in the vitamin sample. The estimated rate of monozygotic twins was higher
      after periconceptional multivitamin supplementation. The number of informative
      pregnancies using vitamin and trace elements was 2104 and 2052, respectively. The
      rate of cases with congenital abnormality was significantly higher in the total
      trace element sample (22.4 per 1000) than in the total vitamin sample (13.3 per
      1000).

PMID- 8257483
TI  - Laser microprobe analysis of brain aluminum in Alzheimer's disease.
AB  - Aluminum (Al) levels were measured in the cytoplasm and nucleus of 241
      neurofibrillary tangle (NFT)-bearing neurons, in 217 NFT-free neurons and
      adjacent neuropil from 7 autopsy-confirmed Alzheimer's disease (AD) patients, and
      in 316 normal neurons from 5 control subjects, by laser microprobe mass
      spectrometry. Grand mean Al levels (dry weight basis) in AD samples were 2.93 +/-
      1.24 micrograms/gm for NFT-bearing neuron cytoplasm, 3.54 +/- 1.39 micrograms/gm
      for NFT-bearing neuron nuclei, 2.31 +/- 1.09 micrograms/gm for NFT-free neuron
      cytoplasm, and 3.23 +/- 1.09 micrograms/gm for NFT-free neuron nuclei. Control
      values were 1.85 +/- 0.78 micrograms/gm for cytoplasm and 2.01 +/- 0.93
      micrograms/gm for nuclei. The differences between corresponding regions of AD NFT
      bearing, AD NFT-free, and control neurons were not significant (p > 0.05,
      analysis of variance). Al levels in neuropil were identical for AD and control
      samples at 2.16 +/- 0.93 micrograms/gm. In contrast to some literature reports,
      we found very few (< 2.5%) extremely high Al values (> 20 micrograms/gm, dry
      weight) on a cellular basis in AD samples. AD neurons did exhibit a higher number
      of Al values (9.6-14.3%) that were > 3 sigma above the corresponding control
      means, than did control neurons (1.3-1.6%), indicating that small elevations of
      Al may exist in patients with AD. Our data suggest that any Al accumulation in
      patients with AD is small and generalized in both NFT-free and NFT-bearing
      neurons and that analyses of large bulk brain samples are likely to have
      AD/control differences masked by the large amount of unaffected neuropil sampled.

PMID- 8257484
TI  - Thrombolytic therapy for myocardial infarction. Treatment introduced in northern
      Ontario.
AB  - In remote regions of Canada, most patients with acute myocardial infarctions (MI)
      are treated by general practitioners. In hospitals served by cardiologists,
      intravenous thrombolytic therapy for MI is now routinely available. In a survey
      of northern Ontario general hospitals, 32 of 45 offered IV thrombolytic therapy.
      The use of streptokinase in one family physician-run hospital was also reviewed.

PMID- 8257485
TI  - Screening for asymptomatic diseases in your patients. Practical tips for doing it
      right.
AB  - Ms. Smith is a 64-year-old white woman who comes to the office for a "check-up."
      She has had a slight "weight problem" and some "high blood pressure," but has
      been in otherwise good health. She is 64 inches tall, weighs 186 pounds, and her
      blood pressure is 145/90. At the conclusion of an otherwise normal exam, the
      topic of health screening regarding breast cancer comes up. She declines a
      mammogram stating that she checks herself "pretty often" and that no other
      physician has ever felt lumps. Besides, she is "too old to worry about getting
      mammograms now," and one of her best friends told her that mammograms "really
      hurt bad."

PMID- 8257486
TI  - Unlicensed practice.

PMID- 8257487
TI  - Powerful bactericidal activities of clarithromycin and minocycline against
      Mycobacterium leprae in lepromatous leprosy.
AB  - Thirty-six patients with newly diagnosed lepromatous leprosy were allocated
      randomly to three groups and treated for 56 days with minocycline (100 mg daily),
      clarithromycin (500 mg daily), or clarithromycin (500 mg) plus minocycline (100
      mg daily). All groups had rapid and remarkable clinical improvement and
      significant decline of the bacterial and morphologic indices in skin smears
      during treatment. More than 99% and > 99.9% of the viable Mycobacterium leprae
      had been killed by 28 and 56 days of treatment, respectively, as measured by
      inoculation of organisms recovered from skin samples, taken before and during
      treatment, into the footpads of immunocompetent and nude mice. Clinical
      improvement and bactericidal activity did not differ significantly among the
      three groups. Adverse reactions were rare and mild, and no laboratory abnormality
      was detected during the trial. Both clarithromycin and minocycline displayed
      powerful bactericidal activities against M. leprae in leprosy patients and may be
      considered important components of new multidrug regimens for the treatment of
      multibacillary leprosy.

PMID- 8257488
TI  - Competition and the death of science.

PMID- 8257489
TI  - Travellers' diarrhoea.

PMID- 8257490
TI  - Damage to DNA in cervical epithelium related to smoking tobacco.
AB  - OBJECTIVE: To determine whether tobacco smoking causes increased DNA modification
      (adducts) in human cervical epithelium. DESIGN: Comparison of DNA adducts
      measured by the technique of postlabelling with phosphorus-32 in normal
      ectocervical epithelium of smokers and non-smokers. A questionnaire on smoking
      habit and a urinary cotinine assay were used to identify smokers and non-smokers.
      SETTING: Cytology unit in large teaching hospital. SUBJECTS: 39 women (11 current
      smokers, seven former smokers, and 21 who had never smoked) undergoing
      gynaecological treatment (colposcopy or hysterectomy). Nineteen members of staff
      who did not smoke as controls. INTERVENTIONS: Biopsy of normal ectocervical
      epithelium. Urine sample. MAIN OUTCOME MEASURES: Measurement of DNA adducts in
      cervical epithelial tissue of smokers and non-smokers. Smoking habit derived from
      results of questionnaire and urinary cotinine:creatinine ratio. Proportion of
      adducts in women with abnormal and normal results of cervical smear test.
      RESULTS: DNA samples from smokers (identified from questionnaire) had
      significantly higher median proportions of DNA adducts that non-smokers (4.62
      (95% confidence interval 4.04 to 7.74) v 3.47 (2.84 to 4.78) adducts/10(8)
      nucleotides; p = 0.048). Exclusion of women whose urinary cotinine:creatinine
      ratio did not confirm their self reported smoking habit (smoker or non-smoker)
      increased this difference (4.7 (3.85 to 8.08) v 3.52 (2.32 to 4.95) adducts/10(8)
      nucleotides; p = 0.03). Women who had abnormal results of cervical smear tests
      had significantly higher proportions of adducts than those with normal results
      (4.7 (3.90 to 8.13) v 3.47 (3.06 to 5.36) adducts/10(8) nucleotides; p = 0.03).
      CONCLUSIONS: Tobacco smoking by women leads to increased modification of DNA in
      cervical epithelium, suggesting biochemical evidence consistent with smoking as a
      cause of cervical cancer.

PMID- 8257491
TI  - Rationing in practice: the case of in vitro fertilisation.
AB  - One of the few examples of explicit rationing in the National Health Service is
      provided by in vitro fertilisation. Of six purchasing authorities examined three
      have decided against buying in vitro fertilisation while three have decided in
      favour. The decisions reflect local factors such as the absence or presence of
      local providers and the views of the public and health professionals. But in
      vitro fertilisation also illustrates some of the wider issues involved in all
      decisions about purchasing: questions about what should be provided by the
      National Health Service, about what procedures should be compared when weighing
      up value for money, and whether equity demands national decisions about what to
      provide.

PMID- 8257492
TI  - The pharmacokinetics of recombinant human relaxin in nonpregnant women after
      intravenous, intravaginal, and intracervical administration.
AB  - The pharmacokinetics of recombinant human relaxin (rhRlx) after intravenous (iv)
      bolus administration and the absorption of rhRlx after intracervical or
      intravaginal administration were determined in nonpregnant women. The study was
      conducted in two parts. In part I, 25 women received 0.01 mg/kg rhRlx iv. After a
      minimum 7-day washout period, these women were dosed intracervically (n = 10) or
      intravaginally (n = 15) with 0.75 or 1.5 mg rhRlx, respectively, in 3%
      methylcellulose gel. Part II was a double-blind, randomized, three-way crossover
      study in 26 women. At 1-month intervals, each woman received one of three
      intravaginal treatments consisting of 0 (placebo), 1, or 6 mg rhRlx in 3%
      methylcellulose gel. The serum concentrations of relaxin following iv
      administration were described as the sum of three exponentials. The mean (+/- SD)
      initial, intermediate, and terminal half-lives were 0.09 +/- 0.04, 0.72 +/- 0.11,
      and 4.6 +/- 1.2 hr, respectively. Most of the area under the curve was associated
      with the intermediate half-life. The weight-normalized clearance was 170 +/- 50
      mL/hr/kg. The observed peak concentration was 98 +/- 29 ng/mL, and the weight
      normalized initial volume of distribution was 78 +/- 40 mL/kg, which is
      approximately equivalent to the serum volume. If central compartment elimination
      was assumed, the volume of distribution at steady state (Vss/W) was 280 +/- 100
      mL/kg, which is approximately equivalent to extracellular fluid volume. Vss/W
      could be as large as 1300 +/- 400 mL/kg without this assumption.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257493
TI  - Straight wire: the next generation.
AB  - Frequently, the anticipated results of treatment are not achieved by using
      preadjusted appliances and straight wires. This is due to inaccurate bracket
      placement, variations in tooth structure, variations in the maxillary/mandibular
      relationships, tissue rebound, and mechanical deficiencies of edgewise
      orthodontic appliances. Clearly, one preadjusted appliance prescription cannot
      fit all orthodontic patients. Individualized prescriptions for preadjusted
      orthodontic appliances can be fabricated once all of these reasons are
      recognized. From the cephalogram and visual treatment objective, the desired
      position of maxillary and mandibular incisors can be determined according to the
      maxillary/mandibular relationships. The torque angle of the labial surface of
      maxillary and mandibular incisors relative to the arch wire plane can be measured
      with an incisor torque template. The development and refinement of a system to
      vary the orientation of the bracket arch wire slot relative to the labial surface
      of each tooth provides a solution to these problems. Beyond the accuracy or
      inaccuracy of bracket placement and the fact that brackets are placed away from
      the center of resistance, orthodontic appliances have two additional significant
      mechanical deficiencies; play between the arch wire and the arch wire slot, and
      force diminution. These deficiencies cannot be eliminated from current
      appliances, however, they can be minimized by using reasonably stiff arch wires
      approximating the size of the arch wire slots. The amount of play plus the amount
      of force diminution inherent in your appliance can be added to or subtracted from
      the torque, tip, rotation, and height parameters for each bracket to deliver the
      teeth to the desired positions. Therefore treatment goals can be achieved with
      maximum efficiency.

PMID- 8257494
TI  - ABC of one to seven. Febrile convulsions.

PMID- 8257495
TI  - Left main coronary aneurysm.

PMID- 8257496
TI  - Yet another use for the Touhy-Borst system.

PMID- 8257497
TI  - Densitometer designed pressure-sensitive film.

PMID- 8257498
TI  - Education in the NICU.

PMID- 8257499
TI  - Physicians need to encourage responsibility, not gun control.

PMID- 8257500
TI  - Somatic symptoms, fear, and panic.

PMID- 8257501
TI  - Appropriateness of cardiac surgery in the elderly.

PMID- 8257502
TI  - Long-term antidepressant treatment in the elderly.

PMID- 8257503
TI  - Measures of postural sway.

PMID- 8257504
TI  - Modifying stature estimation from the femur and tibia.

PMID- 8257505
TI  - Rethinking management of localized neuroblastoma.

PMID- 8257506
TI  - Labeling of antibodies with technetium-99m.

PMID- 8257507
TI  - Bone marrow transplantation for leukemia.

PMID- 8257508
TI  - Intraocular pressure fluctuations.

PMID- 8257509
TI  - Post-operative wound infections in Belize.

PMID- 8257510
TI  - 'Windows of opportunity' to address patients' concerns: too small and too few?

PMID- 8257511
TI  - Beauty parlor stroke: when a beautician becomes a physician.

PMID- 8257512
TI  - Mitochondrial abnormalities in oculopharyngeal muscular dystrophy.

PMID- 8257513
TI  - The marketplace in health care reform.

PMID- 8257514
TI  - Amniotomy in labor.

PMID- 8257515
TI  - A historical review of heart failure. J. Nolan SMJ 1993; 38:53.

PMID- 8257516
TI  - Multiresistant typhoid fever in Bangladesh.

PMID- 8257517
TI  - Acute basophilic leukemia and acute eosinophilic leukemia after therapy for non
      Hodgkin's lymphoma.

PMID- 8257518
TI  - Re: R. Peto et al., Effects on 4080 rats of chronic ingestion of N
      nitrosodiethylamine or N-nitrosodimethylamine: a detailed dose-response study.
      Cancer Res., 51: 6415-6451, 1991, and K. S. Crump et al., Fundamental
      carcinogenic processes and their implications for low dose risk assessment.
      Cancer Res., 36: 2973-2979, 1976.

PMID- 8257519
TI  - BSAC guidelines on sensitivity testing.

PMID- 8257520
TI  - Ball-valve and cyst formation.

PMID- 8257521
TI  - Old times: nasty, brutish, and short--but at least no injected pharmaceuticals.

PMID- 8257522
TI  - Importance of the bronchial circulation in preserving lung function.

PMID- 8257523
TI  - Management of chronic obstructive pulmonary disease.

PMID- 8257524
TI  - Determining whitefly species.

PMID- 8257525
TI  - Treatment of gastrointestinal motility disorders in pregnancy.

PMID- 8257526
TI  - Ondansetron versus metoclopramide and droperidol: an unfair comparison.

PMID- 8257528
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 40-1993. A 61-year-old woman with jaundice, anemia,
      thrombocytopenia, and leukocytosis.

PMID- 8257527
TI  - Pretreatment with somatostatin analog SMS 201-995 potentiates growth hormone (GH)
      responsiveness to GH-releasing factor in short children.
AB  - Previous studies in children have shown inconsistent, poorly reproducible GH
      responses to exogenous GH-releasing factor (GRF), with wide individual
      variability. In the present study, we tested the hypothesis that prior
      administration of the long-acting somatostatin analog, SMS 201-995 (SMS), will
      enhance GH responsiveness to a subsequent GRF challenge. Two study protocols were
      employed in 37 children with short stature [M = 31, F = 6, ages 11.8 +/- 1.6 yr
      (mean +/- SEM), height -2.25 +/- 0.55 SDS (SD scores)]. In both studies, each
      subject served as his/her own control. In the first study, which was designed to
      determine optimal SMS dose and regimen, SMS, in doses ranging from 0.8-2.2
      micrograms/kg sc, was randomly administered or omitted at 0800 h after an
      overnight fast, and a GRF bolus (50 micrograms, iv) was given 4 h later. In the
      second study, we employed a protocol identical to study 1 except for the use of
      standard doses of SMS (1 microgram/kg, sc) and GRF (1 microgram/kg, iv) and an
      additional 1-h delay of the GRF injection. Plasma GH levels were measured every
      20 min from 0800 h until 2 h after the GRF injection in both studies. In study 1
      (n = 12; M = 10, F = 2), SMS significantly suppressed spontaneous GH secretion
      (expressed as the mean +/- SEM GH AUC during the 4-h SMS-GRF interval, AUC 1:2.2
      +/- 0.4 vs. 6.2 +/- 0.9 micrograms/L.h; P < 0.001), GH responsiveness to GRF (GH
      AUC during the 2 h after the GRF injection, AUC 2: 41.5 +/- 7.8 vs. 85.0 +/- 13.5
      micrograms/L.h; P < 0.001), and the GH peak response (17.4 +/- 3.1 vs. 36.0 +/-
      6.2 micrograms/L; P < 0.001), compared to control tests. In contrast, in study 2
      (n = 25; M = 21, F = 4), whereas spontaneous GH secretion was still suppressed
      during the 5-h SMS-GRF interval (AUC 1:3.8 +/- 0.4 vs. 7.4 +/- 1.1
      micrograms/L.h; P < 0.001), both the GH peak response (56.7 +/- 5.5 vs. 30.5 +/-
      3.0 micrograms/L; P < 0.0001) and the GH AUC (AUC 2: 103.7 +/- 10.3 vs. 77.5 +/-
      6.8 micrograms/L.h; P < 0.05) after GRF administration were significantly
      augmented by pretreatment with SMS, compared to control tests. Taken together,
      these results indicate that a priming SMS dose of 1 microgram/kg has a
      significant permissive effect on GH responsiveness to exogenous GRF administered
      5 h later.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8257529
TI  - Determining the ideal of continuity of care.

PMID- 8257530
TI  - Travellers' diarrhea. Consider enteral immunotherapy.

PMID- 8257531
TI  - Cancer support services in the voluntary sector.

PMID- 8257532
TI  - Interpreting inflammatory changes in cervical smears.

PMID- 8257533
TI  - Health in the developing world. Health loses out to the arms trade.

PMID- 8257534
TI  - The Somers plan: an early managed competition proposal.

PMID- 8257535
TI  - Immobilisation for scaphoid fractures.

PMID- 8257536
TI  - The role of optometrists in dealing with patients suffering from visual
      impairments.

PMID- 8257537
TI  - DNR policy.

PMID- 8257538
TI  - Oxygen desaturation during endoscopy in the elderly.

PMID- 8257539
TI  - Liability for failure to diagnose HIV infection.

PMID- 8257540
TI  - Medicine at the fringes.

PMID- 8257541
TI  - Developmentally disabled people as a culture.

PMID- 8257542
TI  - Acute effects of mycoprotein on subsequent energy intake and appetite variables.
AB  - The effect of mycoprotein, a food produced by continuous fermentation of Fusarium
      graminearum (Schwabe), on energy intake and appetite was investigated. Female
      subjects, all classified as nonrestrained eaters, participated in two 3-d study
      periods. Subjects weighed food consumed on the day before the study, on the day
      of the meal, and on the following day. Subjects were presented with an
      isoenergetic meal containing either mycoprotein or chicken and visual analogue
      scales were completed immediately premeal, postmeal, and at hourly intervals for
      3 h. Energy intake was significantly reduced the day of the study (by 24%) and
      the next day (by 16.5%) after eating mycoprotein compared with chicken. When
      measured 3 h after consumption, prospective food consumption and desire to eat
      decreased after mycoprotein compared with chicken. Evidence is increasing that
      fiber can have an effect on appetite and we have demonstrated that fiber
      containing mycoprotein also has this affect.

PMID- 8257543
TI  - Nutritionists in the Third World.

PMID- 8257544
TI  - Nutrition engineer.

PMID- 8257545
TI  - Prazosin, diuretics, and glucose intolerance.

PMID- 8257546
TI  - Surgical face masks: protection for self or patient?

PMID- 8257547
TI  - Differential pulse voltammetric determination of 7-hydroxycoumarin in human
      urine.
AB  - The electrochemical behaviour of 7-OH-coumarin at the bare glassy carbon
      electrode has been studied using differential pulse voltammetry, and based on
      anodic detection of this metabolite at 0.66 V (vs SCE) using DC amperometry, a
      method has been developed for the determination of 7-OH-coumarin levels in urine
      samples, and a pharmacokinetic profile established.

PMID- 8257548
TI  - Spontaneous bacterial peritonitis due to Neisseria meningitidis serogroup Z.

PMID- 8257549
TI  - Determination of gastroduodenal permeability.

PMID- 8257550
TI  - Comparison of two local anaesthetics in transvaginal ultrasound-guided oocyte
      retrieval.
AB  - Transvaginal ultrasound-guided oocyte retrieval is an accepted procedure in most
      in-vitro fertilization programmes. In order to simplify the anaesthetic procedure
      into a minimally invasive one, we perform the oocyte retrieval under a modified
      para-cervical block combined with a standard pre-medication. In order to maximize
      the patient's comfort we evaluated two different local anaesthetics and their
      side-effects. Patients were allocated at random to receive a modified para
      cervical block with mepivacaine 1% (n = 46) or with prilocaine 1% (n = 54). The
      patients were asked to fill in a visual analogue scale (VAS) including assessment
      of anxiety, pain and comfort concerning the procedure. The two local anaesthetics
      were both effective in reducing pain during transvaginal oocyte retrieval. The
      mean VAS scores were acceptable and were efficient as indicators of patient's
      comfort during the procedure. Mepivacaine was selected for routine use since
      prilocaine induced methaemoglobinaemia.

PMID- 8257551
TI  - Buprenorphine in opiate withdrawal: a comparison with clonidine.
AB  - Clinical efficacy of buprenorphine in controlling withdrawal symptoms was
      compared against clonidine among 44 opiate dependent males. Subjective and
      objective withdrawal symptoms were assessed by withdrawal rating scales daily for
      10 days. The subjects were randomly assigned to fixed dose schedule of either
      buprenorphine (0.6-1.2 mg per day, sublingually) or clonidine (0.3-0.9 mg per
      day, oral) for 10 days. Buprenorphine was found superior to clonidine in
      alleviating most of the subjective and objective opiate withdrawal symptoms.
      Subjective symptoms declined earlier among the subjects receiving buprenorphine.
      No untoward side-effects of buprenorphine were noticed.

PMID- 8257552
TI  - Varicella-zoster vaccine.

PMID- 8257553
TI  - Walking--aspects of homelessness.

PMID- 8257554
TI  - Vitamin E and the risk of coronary disease.

PMID- 8257555
TI  - Brodmann's numbers.

PMID- 8257556
TI  - Psychogenic myoclonus.

PMID- 8257557
TI  - Epidemiologic evidence for a causal relation between vaccination and fibrosarcoma
      tumorigenesis in cats.
AB  - Within the past 2 years, a putative causal relationship has been reported between
      vaccination against rabies and the development of fibrosarcomas at injection
      sites in cats. A retrospective study was undertaken, involving 345 cats with
      fibrosarcomas diagnosed between January 1991 and May 1992, to assess the causal
      hypothesis. Cats with fibrosarcomas developing at body locations where vaccines
      are typically administered (n = 185) were compared with controls (n = 160) having
      fibrosarcomas at locations not typically used for vaccination. In cats receiving
      FeLV vaccination within 2 years of tumorigenesis, the time between vaccination
      and tumor development was significantly (P = 0.005) shorter for tumors developing
      at sites where vaccines are typically administered than for tumors at other
      sites. Univariate analysis, adjusted for age, revealed associations between FeLV
      vaccination (odds ratio [OR] = 2.82; 95% confidence interval [CI] = 1.54 to
      5.15), rabies vaccination at the cervical/interscapular region (OR = 2.09; 95% CI
      = 1.01 to 4.31), and rabies vaccination at the femoral region (OR = 1.83; 95% CI
      = 0.65 to 5.10) with fibrosarcoma development at the vaccination site within 1
      year of vaccination. Multivariate analysis, adjusted for age and other vaccines,
      also revealed increased risks after FeLV (OR = 5.49; 95% CI = 1.98 to 15.24) and
      rabies (OR = 1.99; 95% CI = 0.72 to 5.54) vaccination.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8257558
TI  - The expression of rat GAP-43 cDNA in transgenic carp.
AB  - To understand more about growth-associated protein-43 (GAP-43), we produced
      transgenic carp by introduction of a rat GAP-43 cDNA linked to the Rous sarcoma
      virus-long terminal repeat into fertilized eggs. Of 180 eggs microinjected with
      exogenous gene, 59 embryos hatched and 4 fish were found to contain the exogenous
      gene sequences in the genomic DNA. From a mature female transgenic carp,
      parthenogenetically, 126 progeny were derived and 52 of them survived for more
      than 90 days. The exogenous gene sequences were detected in 22 F1 progeny, and
      its messenger RNA was detected in all of 10 transgenic F1 carp examined. In serum
      free medium, cultured retinal ganglion cells isolated from transgenic carp
      elongated their axons, while non-transgenic cells did not elongate axons.

PMID- 8257559
TI  - Two major signal pathways linked.

PMID- 8257560
TI  - Hydration forces.

PMID- 8257561
TI  - Pressure stability of proteins.

PMID- 8257562
TI  - Differential expression of insulin-like growth factor-II in specific regions of
      the late (post day 9.5) murine placenta.
AB  - Insulin-like growth factor-II (IGF-II) expression has been implicated as a major
      determinant of fetal size during murine pregnancy. It remains unclear whether
      expression in the fetus, the placenta, or both is the overriding factor
      controlling growth. To gain further understanding of the placental contribution,
      we mapped IGF-II expression in the fetal vascular and trophoblastic portions of
      the late murine placenta (day 9.5-18.5). We found that, as in the fetus itself,
      vasculogenic mesenchyme, in this case derived from the allantois, was the
      strongest expressor of IGF-II. Trophoblast, on the other hand, while expressing
      somewhat less IGF-II, showed a dynamic pattern of IGF-II expression, which
      reflected its continuing differentiation during late pregnancy. Initially (days
      9.5 and 12.5), the spongiotrophoblast, which is homologous to the cytotrophoblast
      columns and shell in early human pregnancy, strongly expressed IGF-II. Later,
      expression in the spongiotrophoblast was down-regulated as a new population, the
      so-called glycogen cells, emerged within the spongiotrophoblast (day 12.5-15.5)
      and went on to invade the mesometrial decidua. Glycogen cells, which are
      homologous to human intermediate trophoblast, strongly expressed IGF-II.
      Trophoblast lining the area of maternal-fetal exchange, the labyrinth, on the
      other hand, maintained a constitutive lower level of IGF-II expression throughout
      late pregnancy.

PMID- 8257563
TI  - Pluripotency of cultured rabbit inner cell mass cells detected by isozyme
      analysis and eye pigmentation of fetuses following injection into blastocysts or
      morulae.
AB  - Pluripotency of isolated rabbit inner cell masses (ICMs) and cultured (3 days)
      inner cell mass (ICM) cells was tested by injecting these donor cells into day
      3.5 blastocysts (experiment 1) or day 3 morulae (experiment 2) to produce
      chimeric embryos. Injected (n = 107) and noninjected (n = 103) embryos were
      transferred to the opposite uterine horns of the same recipient females.
      Chimerism was determined by adenosine deaminase (ADA) isozyme analysis on fetal
      tissue and by eye pigmentation at midgestation. In experiment 1, 53% and 64%,
      respectively, of blastocysts injected with ICMs or cultured ICM cells developed
      to midgestation, compared with 52% and 48% for controls. Of these fetuses, four
      (31%) and one (6%), respectively, had ADA chimerism. In experiment 2, 38% and
      62%, respectively, of the morulae injected with ICMs or cultured ICM cells
      developed to midgestation, compared with 46% and 56% for control morulae. Six
      (43%) chimeric fetuses from morulae injected with ICMs were detected by ADA
      analysis, but 12 (86%) chimeric fetuses were detected by eye pigmentation,
      indicating that eye pigmentation was a more sensitive marker for chimerism than
      our ADA assay. None of the 14 fetuses recovered after injecting morulae with
      cultured ICM cells were chimeric with either marker. No chimeras developed from
      control embryos. These studies demonstrate 1) that pregnancy rates are not
      compromised by injection of blastocysts or morulae with ICMs or cultured ICM
      cells, 2) that chimeric rabbit fetuses can be produced by injecting ICMs into
      either blastocysts or morulae, and 3) that cultured ICM cells can contribute to
      embryonic development when injected into blastocysts.

PMID- 8257564
TI  - Embryonic stem cells derived from morulae, inner cell mass, and blastocysts of
      mink: comparisons of their pluripotencies.
AB  - A characterization of cell lines that we derived from morulae (three lines),
      blastocysts (two lines), and the inner cell mass (ICM) is given. The karyotype of
      all the lines was normal; the genotype of four lines was XX, and four lines were
      genotypically XY. The pluripotencies and commitment status of the derived lines
      were estimated. First, there were not less than two-thirds of cells in the
      populations of the lines derived from morulae and the ICM with both Xs active; 70
      100% of cells of the blastocyst-derived lines had one of the Xs in an inactive
      state. The activity of glucose-6-phosphate dehydrogenase (G6PD) in the lines
      (genotype XX) derived from morulae and ICM was found to be twofold higher than in
      lines with genotype XY, and G6PD activity was the same in the blastocyst-derived
      XX lines and XY lines. Second, when injected intraperitoneally into athymic mice,
      morulae- and ICM-derived cells gave rise to simple and complex embryoid bodies
      (EB) resembling to typical "cystic" mouse EBs. Third, when injected
      subcutaneously to athymic mice, the ICM- or morula-derived cells gave rise to
      typical teratomas containing derivatives of the three germ layers and components
      of organogenesis. Comparisons of cell lines of different derivations demonstrated
      that the pluripotencies of the ES cells derived from morulae or the ICM are
      higher than those of blastocyst derivation.

PMID- 8257565
TI  - Evidence for the production of a growth-inhibitory factor by human granulosa
      luteal cells.
AB  - The factors involved in the inhibition of ovarian follicular cellular growth
      after the luteinizing hormone (LH) surge are poorly established. The aim of this
      study was to investigate the production of an inhibitory growth factor by human
      ovarian cells. Luteinized granulosa cells were obtained from an assisted
      fertilization program and were cultured in the presence or absence of follicle
      stimulating hormone (FSH) and estradiol. Data obtained by cell counting showed
      that the number of human luteinized granulosa cells cultured in the presence of
      fetal bovine serum (10%) increased 1.8-fold within a 2-day period. In serum-free
      medium, human luteinized granulosa cells were able to incorporate 3H-thymidine,
      measured during consecutive 48 h periods. During all the periods tested (up to 7
      days), low basal levels of thymidine incorporation were measured and were further
      reduced in the presence of FSH (200 ng/ml) and estradiol (500 ng/ml). To
      elucidate the possible production of an inhibitory growth factor, 3H-thymidine
      incorporation by rat granulosa cell cultures was measured in the presence of
      conditioned media (CM; from human granulosa cell cultures). In this system, FSH
      and estradiol elicited a tenfold increase in thymidine incorporation. The
      addition of CM (10% v/v collected on day 2) to FSH- and estradiol-treated
      granulosa cell cultures produced an inhibition (61%) of thymidine incorporation.
      The active factor in CM withstood freeze-thawing, was stable for several weeks at
      -20 degrees C, became unstable at 4 degrees C, and was heat labile and sensitive
      to proteolysis. Ultrafiltration using membranes with different molecular weight
      cutoffs suggested that the factor had a molecular weight > 30,000
      dalton.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257566
TI  - The abundant 19-kilodalton protein associated with human sperm nuclei that is
      related to seminal plasma alpha-inhibins.
AB  - A basic protein with a relative molecular mass of 19 kDa has been identified and
      isolated to purity from sonication-resistant, partially demembranized human sperm
      nuclei. Several criteria prove that this is the unique sperm-specific protein,
      which was previously thought to be a sperm/testis histone. Partial primary
      structure sequencing demonstrates homologies with human seminal alpha-inhibins
      and semenogelin. From the sequence and Western-blotting data with antibodies
      against basic seminal inhibin-like peptide, we propose that this 19-kD protein is
      a product of 52-kDa semenogelin processing. The 19-kDa protein was not found
      among seminal plasma proteins and may be protected from further cleavage into
      inhibin-like peptides by its association with the sperm head. Immunofluorescence
      data indicate its localization in the nuclear periphery, with preferential
      concentration at the acrosome calyx boundary.

PMID- 8257567
TI  - Evaluation of mouse sperm acrosomal status and viability by flow cytometry.
AB  - A procedure was developed to evaluate mouse sperm acrosomal status and viability
      simultaneously utilizing flow cytometry. Four fluorescein isothiocyanate (FITC)
      conjugated lectins, peanut agglutinin (PNA), concanavalin agglutinin (ConA),
      Pisum sativum agglutinin (PSA), and soybean agglutinin (SBA), were investigated,
      with PNA providing the greatest sensitivity and specificity in distinguishing
      acrosome-present and acrosome-absent mouse spermatozoa. To expose lectin binding
      sites, digitonin (20 microM at room temperature for 10 min) was used to
      permeabilize sperm plasma membranes. Sperm cell viability was determined by
      Hoechst 33258-(H258) exclusion. To prevent permeabilized cells from staining with
      H258, salmon sperm DNA (SS-DNA) was applied to bind excess dye in the solutions
      after supravital staining. Calcium ionophore (A23187; 5 or 20 microM) was used to
      induce acrosome reactions. The results of flow cytometric analyses were compared
      with epifluorescence microscopic observation and were highly correlated (r =
      0.999; P < 0.001). The method developed provides an objective and efficient
      procedure to estimate simultaneously both acrosomal status and viability of mouse
      spermatozoa.

PMID- 8257568
TI  - Surface-associated glycosyltransferase activities in rat Sertoli cells in vitro.
AB  - We have previously demonstrated fucosyltransferase (FT) activity on mouse germ
      cell surfaces at different stages of spermatogenesis. To complement these
      findings, here we report FT activity on the Sertoli cell (SC) surface. SC
      isolated and cultured from 20-day-old rat testes displayed FT activity with a
      Vmax of 12.5 pmoles/mg protein/min and a Km of 22 microM, while purified Sertoli
      cell plasma membranes (SCPM) showed FT activity with a Vmax of 10 pmoles/mg
      protein/min and a Km of 18.2 microM for GDP-[14C]-L-fucose. Fucosyltransferase
      activities were 16.7 and 2.6 pmoles/mg protein/min in SC and SCPM, respectively;
      approximately 16% of FT activity is, therefore, on the cell surface. To test
      whether the expression of FT activity in SC was regulated by hormones and growth
      factors, SC were cultured in serum-free medium supplemented with insulin,
      transferrin, sodium selenite, and epidermal growth factor (medium 4F) or in 4F
      plus follicle-stimulating hormone, testosterone, hydrocortisone, and vitamin E
      (medium 8F). We found that FT activity in SC is not modulated by these hormones
      or growth factors (4F or 8F). For comparison with FT, galactosyltransferase
      (GalTase) activities in SC and SCPM were also determined. SC displayed GalTase
      activity with a Vmax of 50 pmoles/mg protein/min and a Km of 38.5 microM, while
      SCPM showed GalTase activity with a Vmax of 25 pmoles/mg protein/min and a Km of
      20.8 microM for UDP-[3H]-galactose. Galactosyl-transferase activities were 29.2
      and 9.6 pmoles/mg protein/min in SC and SCPM, respectively. Therefore,
      approximately 33% of the total cell GalTase activity was detected on the surface
      membranes of rat Sertoli cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257569
TI  - Actin polymerization in boar spermatozoa: fertilization is reduced with use of
      cytochalasin D.
AB  - The aggregational state of actin in boar spermatozoa after capacitation and the
      acrosome reaction has been examined by several methods. In vitro fertilization
      (IVF) experiments were conducted in the presence and absence of cytochalasin D
      (CD) to evaluate the role of actin polymerization in the events of fertilization.
      The fertilizing capacity was very high in controls, but, when CD (an inhibitor of
      the polymerization of actin) was added to the capacitation medium, there was a
      marked decrease in the fertilizing capacity of the boar spermatozoa. There was a
      further decrease when CD was present during both capacitation and fertilization
      processes. In addition to the IVF tests, biochemical and immunoelectron
      microscopic methods were used to analyze the state of aggregation of actin in
      boar spermatozoa after capacitation, and the acrosome reaction. By immunoelectron
      microscopy with a phalloidin probe, there were no gold particles, indicating the
      presence of F-actin on boar sperm heads capacitated and acrosome-reacted in media
      containing CD. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis there
      were differences in NP-40 solubility, reflecting actin polymerization, between CD
      treated and untreated sperm. These results suggest that actin polymerizes during
      capacitation and the acrosome reaction and that this polymerization is essential
      to the fertilization process.

PMID- 8257570
TI  - Mammalian oocytes exhibit specific recognition of the RGD (Arg-Gly-Asp)
      tripeptide and express oolemmal integrins.
AB  - Integrins are a family of cell adhesion receptors involved in many cell-cell and
      cell-matrix interactions. Some of these heterodimeric receptors, such as alpha 5
      beta 1 and alpha v beta 1, specifically recognize the amino acid sequence Arg-Gly
      Asp (RGD) within their ligands. The RGD sequence is found in fibronectin,
      vitronectin, and other extracellular matrix proteins. Our results demonstrate
      that the oolemmas of eggs from human and several other mammalian species contain
      receptors capable of binding to RGD ligands, and that integrin subunits are
      expressed by oocytes. Four distinct techniques were utilized to identify the
      presence of functional integrins on mammalian eggs. RGD-binding receptors were
      detected on the surfaces of zona-free eggs from all species tested. Covaspheres
      coated with PepTite-2000, which contains RGD, bound to the eggs and formed
      rosettes. Rosetting was competitively inhibited by PepTite-2000 and by GRGDTP, a
      soluble RGD peptide, but not by RGES. An ELISA using polyclonal antibodies
      directed against the cytoplasmic tails of the integrin subunits identified the
      integrin subunits alpha 5, beta 1, and alpha v, but not beta 3, in detergent
      extracts of Syrian hamster eggs. A dot blot confirmed the presence of alpha v in
      hamster egg lysates. Finally, the integrin subunits alpha 2, alpha 5, alpha 6,
      but not alpha 4, were detected on the surfaces of zona-free eggs from human and
      Syrian hamster. Immunobeads coated with monoclonal antibodies specific for alpha
      2, alpha 5, and alpha 6 bound to the eggs and formed rosettes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8257571
TI  - Role of tubulin and dynein in spermatozoan motility.

PMID- 8257572
TI  - Analysis of sperm motility by computer assisted methods, with special
      consideration of in vitro fertilization.

PMID- 8257573
TI  - In vitro fertilization in cattle.

PMID- 8257574
TI  - Cryopreservation of bovine oocytes and embryos following microsurgical
      operations.

PMID- 8257575
TI  - Bovine embryo transfer and related techniques.

PMID- 8257576
TI  - Embryo sexing by male specific antibody and by PCR using male specific (SRY)
      primer.

PMID- 8257577
TI  - Inheritance and tissue-specific expression of transgenes in rabbits and pigs.

PMID- 8257578
TI  - Transgenic mouse model for human genetic diseases.

PMID- 8257579
TI  - Recent progress in the transgenic modification of swine and sheep.

PMID- 8257580
TI  - Recent advances in sperm cell mediated gene transfer.

PMID- 8257581
TI  - Gene transfer in the chicken by sperm-mediated methods.

PMID- 8257582
TI  - Prospects for improving the survival rate of transferred embryos.

PMID- 8257583
TI  - Embryo production: alternative methods.

PMID- 8257584
TI  - Folliculogenesis and oocyte maturation in superovulated cattle.

PMID- 8257585
TI  - Nuclear transfer in cattle.

PMID- 8257586
TI  - Totipotency and pluripotency of embryonic nuclei in the mouse.

PMID- 8257587
TI  - Role of the oviduct in the development of the mouse embryo.

PMID- 8257588
TI  - Rabbit microfertilization.

PMID- 8257589
TI  - Micromanipulation-assisted fertilization.

PMID- 8257590
TI  - Bovine microfertilization and embryo transfer.

PMID- 8257591
TI  - Ozonolysis products of membrane fatty acids activate eicosanoid metabolism in
      human airway epithelial cells.
AB  - When inhaled, ozone reacts at the airway luminal surface with unsaturated fatty
      acids contained in the extracellular fluid and plasma membrane to form an
      aldehyde and hydroxyhydroperoxide. The resulting hydroxyhydroperoxide degrades in
      aqueous systems to yield a second aldehyde and hydrogen peroxide (H2O2).
      Previously, we demonstrated that ozone can augment eicosanoid metabolism in
      bovine airway epithelial cells. To examine structure-activity relationships of
      ozone-fatty acid degradation products on eicosanoid metabolism in human airway
      epithelial cells, 3-, 6-, and 9-carbon saturated aldehydes and
      hydroxyhydroperoxides were synthesized and purified. Eicosanoid metabolism was
      evaluated by determination of total 3H-activity release from confluent cells
      previously incubated with [3H]arachidonic acid and by identification of specific
      metabolites with high performance liquid chromatography and radioimmunoassay. The
      major metabolites detected were prostaglandin E2, prostaglandin F2 alpha, and 15
      hydroxyeicosatetraenoic acid. The 9-carbon aldehyde, nonanal, in contrast to 3-
      or 6-carbon aldehydes, stimulated release at concentrations > or = 100 microM,
      suggesting that the stimulatory effect increases with increasing chain length.
      When tested under identical conditions, the 3-, 6-, and 9-carbon
      hydroxyhydroperoxides were more potent than the corresponding aldehydes. Again, a
      greater effect was noted when the chain length was increased. One possible
      explanation for the increased potency of the hydroxyhydroperoxides over the
      aldehydes could be due to degradation of the hydroxyhydroperoxide into H2O2 and
      aldehyde. We consider this an unlikely explanation because responses varied with
      chain length (although each hydroxyhydroperoxide would produce an equivalent
      amount of H2O2) and because exposure to H2O2 alone or H2O2 plus hexanal produced
      a response dissimilar to 1-hydroxy-1-hexanehydroperoxide.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8257592
TI  - Modulation of hydrogen peroxide release from vascular endothelial cells by
      oxygen.
AB  - We have investigated factors that regulate hydrogen peroxide (H2O2) release from
      vascular endothelial cells. Endothelial cells produce H2O2 at an intracellular
      site in the vicinity of peroxisomes and at a second site near the cell surface
      that is inaccessible to intracellular catalase or glutathione peroxidase.
      Regulation of H2O2 generation at the intracellular site was studied using
      aminotriazole, which inactivates catalase in the presence of H2O2. Regulation of
      H2O2 generation at the second site was studied by measuring H2O2 release into the
      medium. The rate of H2O2 release was constant over 2 h when cells were incubated
      in room air. Changing O2 levels in the atmosphere from 0% to 10% O2 resulted in a
      threefold increase in the rate of H2O2 release. Elevation of O2 levels from 10%
      to 95% O2 produced no further enhancement in the rate of release. Preincubation
      of cells under hypoxic conditions did not lead to an exaggerated rate of H2O2
      release when cells were returned to room air. Pretreatment of cells with
      exogenous H2O2 inhibited subsequent H2O2 release while pretreatment with catalase
      enhanced H2O2 release. Although arachidonic acid transiently enhanced the rate of
      H2O2 release through a mechanism dependent on PGH synthase, basal H2O2 release
      was independent of this enzyme. Neither hypoxia, hyperoxia, or hypoxia followed
      by reoxygenation altered H2O2 generation at the intracellular site accessible to
      peroxisomal catalase. These data demonstrate that H2O2 release from endothelial
      cells is responsive to changes in O2 concentrations over a narrow range. The
      mechanisms involved are subject to product inhibition and appear to be saturated
      at 10% O2 in the atmosphere.

PMID- 8257593
TI  - MnSOD protein content changes in hypoxic/hypoperfused lung tissue.
AB  - Previous studies using an in vivo rabbit model in which lung tissue
      hypoxia/hypoperfusion was created by unilateral lung collapse for 7 days
      demonstrated a decrease in MnSOD activity in previously hypoxic/hypoperfused
      lungs. In the present study, we determined whether tissue hypoxia/hypoperfusion
      decreased MnSOD protein concentration or mRNA expression in the lung as well,
      changes that would suggest pretranslational regulation of enzyme activity.
      Expression of MnSOD may be critical in determining the degree of tissue injury
      during re-oxygenation because the mitochondrial electron transport system
      produces reactive oxygen species (ROS) both during hypoxia and re-oxygenation. We
      purified MnSOD protein from rabbit livers to a specific activity of approximately
      3,500 U/mg protein and found the amino terminal sequence nearly identical to
      those of the rat and human MnSOD proteins. Lung MnSOD protein content was
      quantitated by immunoassay, and MnSOD mRNA content was determined by slot
      blotting. Results from five control and six experimental rabbits, the right lungs
      of which had been hypoxic/hypoperfused because of collapse for 7 days,
      demonstrated a 32% decrease (P < 0.03) in MnSOD protein content (42 +/- 8
      micrograms/mg DNA in hypoxic lungs compared with 61 +/- 3 micrograms/mg DNA in
      contralateral lungs) that was not due to decreased numbers of mitochondria. Lung
      succinate dehydrogenase activity, a mitochondrial marker, did not change in
      hypoxic/hypoperfused lungs. The mRNA for MnSOD did not change relative to B-actin
      mRNA in lungs that had been hypoxic and hypoperfused for 7 days.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257594
TI  - Role for C5 and neutrophils in the pulmonary intravascular clearance of
      circulating Cryptococcus neoformans.
AB  - Although C5a-induced intravascular pulmonary sequestration of neutrophils has
      been investigated with regards to lung injury, relatively few studies have
      addressed the possible role for this mechanism in the intravascular clearance of
      circulating microorganisms. A murine model was used in which the complement
      fixing, encapsulated yeast Cryptococcus neoformans (Cne) was inoculated
      intravenously (IV), and lung clearance of the organism was measured 24 h later.
      In normal mice, clearance was remarkably effective, but in leukocyte-depleted or
      C5-deficient (C5-) animals, clearance was significantly decreased. In vitro
      assays indicated that C5 was necessary for neutrophils to kill encapsulated Cne
      and evidence was obtained that C5a was involved. In vivo studies using light and
      electron microscopy demonstrated that 30 min after an IV inoculation of
      encapsulated yeast into C5-sufficient (C5+) mice, neutrophils accumulated in
      pulmonary vessels and engulfed Cne. However, in C5- mice, neutrophils failed to
      accumulate in pulmonary vessels and there was no endocytosis of encapsulated
      yeasts. These studies suggested that following Cne interaction with complement in
      the blood, release of C5a activated circulating neutrophils to adhere to Cne, and
      perhaps to adjacent endothelium, which facilitated rapid phagocytosis and killing
      of the organism. In contrast to the IV infection model, when Cne was inoculated
      into the tracheas of C5+ and C5- mice, no evidence was obtained for an early PMN
      C5-dependent clearance mechanism. C5a-dependent neutrophil killing in the lung
      vasculature may provide important host protection against Cne during vascular
      dissemination and perhaps against other disseminating microorganisms that
      activate complement.

PMID- 8257595
TI  - Interleukin-1 beta stimulates the proliferation of cultured airway smooth muscle
      cells via platelet-derived growth factor.
AB  - Bronchoalveolar lavage fluid from symptomatic asthmatics contains elevated levels
      of several proinflammatory interleukins including interleukin-1 beta (IL-1 beta).
      Biologic activities of IL-1 beta are considered to be critical in the
      inflammatory process. Since these characteristics include mitogenic properties,
      we investigated the effect of IL-1 beta on the proliferation of airway smooth
      muscle (ASM) cells isolated from guinea pig tracheas. Primary tissue culture of
      ASM cells was maintained in media containing 0%, 1%, or 10% fetal bovine serum
      (FBS). Cultures were exposed up to 6 days to human recombinant IL-1 beta (20, 40,
      or 100 pg/ml) in the presence or absence of indomethacin. The proliferation of
      ASM cells was assessed with two techniques: a direct counting of cells with a
      hemocytometer and/or with a [3H]-thymidine incorporation, an established marker
      of DNA synthesis. The evaluation was done daily, up to the sixth day after
      exposure of cells to different doses of IL-1 beta. We found that the exposure of
      ASM cells to human recombinant IL-1 beta significantly (P < 0.01) increased the
      number of tracheal myocytes as well as the [3H]-thymidine incorporation into ASM
      cells. These changes were dependent upon the dose of IL-1 beta and the
      concentration of FBS in the cultured medium. The most active proliferation of ASM
      cells was observed in medium containing 1% FBS, indomethacin (1 microgram/ml),
      and IL-1 beta (100 pg/ml). The presence of indomethacin in the culture medium was
      essential to demonstrate the proliferative effect of IL-1 beta.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257596
TI  - Pulmonary surfactant inhibits interleukin-2-induced proliferation and the
      generation of lymphokine-activated killer cells.
AB  - The generation of lymphokine-activated killer (LAK) cell activity and the
      proliferative response to human recombinant interleukin-2 (IL-2) were
      significantly reduced when either human peripheral blood lymphocytes (PBL) or
      purified CD56+/CD3- lymphocytes were cultured in the presence of pulmonary
      surfactant. Surfactant concentrations ranging between 30 and 500 micrograms/ml
      produced increasing levels of inhibition ranging from 20 to 95%. For any given
      concentration of surfactant, increasing the IL-2 concentration produced
      increasing levels of LAK activity but never overcame the suppressive effects of
      the surfactant. Time course studies demonstrated that surfactant is inhibitory
      only if added to PBL during the first 2 days of IL-2 culture, suggesting a
      preferential action during the induction phase of LAK activity. Pretreatment of
      PBL with surfactant for as little as 2 to 4 h inhibited their subsequent response
      to IL-2 culture, suggesting that inhibition is rapid, persistent, and directly
      due to alterations in PBL responsiveness. To determine if surfactant alters cell
      membrane function, we measured the effects of surfactant exposure on LAK:tumor
      binding. Binding of LAK cells to both K562 and M14 tumor targets was inhibited in
      a concentration-dependent manner. Concurrently, we observed a reduced expression
      of IL-2 alpha-chain receptors on surfactant-treated CD56+/CD3- cells and a
      dramatic reduction in the expression of adhesion molecules including CD2, LFA-1,
      LFA-3, and ICAM-1. We conclude that pulmonary surfactant has the potential to
      suppress cytotoxic and proliferative responses to IL-2, alters cell-to-cell
      interactions, and reduces the expression of activation and adhesion molecules on
      LAK cells.

PMID- 8257597
TI  - Inhibition of natural killer cell activity by therapeutic levels of theophylline.
AB  - Theophylline, as used for the treatment of asthma and chronic obstructive
      pulmonary disease, may have several effects, including direct bronchodilation,
      improvement in diaphragmatic and ciliary function, and possibly immune
      modulation. In this study, we quantified the capacity for theophylline to inhibit
      natural killer (NK) cells and investigated the mechanism(s) that mediate this
      inhibition. Theophylline at 10 micrograms/ml and 20 micrograms/ml inhibited the
      tumoricidal activity of isolated peripheral blood lymphocytes (PBL) by 19 +/- 5%
      and 36 +/- 6%, respectively (n = 6). Using fluorescence-activated cell sorting,
      we purified NK cells from PBL and tested theophylline's effects on the kinetics
      of tumor lysis (Vmax) and on tumor binding. Theophylline at 20 micrograms/ml
      reduced Vmax by 40 +/- 9% but had no effect on tumor binding. We compared the
      effects of theophylline, which is both a phosphodiesterase (PDE) inhibitor and an
      adenosine receptor (AdR) antagonist, with agents that range from relatively pure
      AdR antagonists to pure PDE inhibitors. Inhibition of NK activity occurred only
      with PDE inhibitors. We also extracted lymphocyte PDE and observed a direct
      correlation (r2 = 0.99) between theophylline's activity as a PDE inhibitor and
      its capacity to inhibit NK activity. These results suggest that theophylline
      inhibits NK cytotoxicity through its activity as a PDE inhibitor. The clinical
      relevance of these findings awaits further study.

PMID- 8257598
TI  - Human alpha 1-proteinase inhibitor binds to extracellular matrix in vitro.
AB  - alpha 1-Proteinase inhibitor (alpha 1-PI) is the major endogenous inhibitor of
      human leukocyte elastase (HLE). We have employed two different methods to
      quantitate the binding of alpha 1-PI to extracellular matrix (ECM), composed of
      51% glycoproteins and proteoglycans, 37% types I and III collagen, and 12%
      elastin, derived from rat heart smooth muscle cells. alpha 1-PI is tightly bound
      to ECM via a saturable adsorption process; the bound protein fails to dissociate
      from the matrix after repeated washing. Binding of alpha 1-PI is unaffected by
      the prior removal of ECM glycoproteins with trypsin. Binding to ECM is not
      decreased in the presence of high salt but is decreased at low pH. A 40-fold
      excess of unlabeled alpha 1-PI displaces only 50% of [125I]alpha 1-PI prebound to
      ECM. A 30% decrease in the levels of alpha 1-PI bound to ECM is observed after
      DTT washes of ECM preincubated with alpha 1-PI or when alpha 1-PI is modified
      with iodoacetamide prior to incubation with ECM, implying that a fraction of
      bound alpha 1-PI is covalently linked to ECM via disulfide bond formation.
      Moreover, high molecular weight complexes between [125I]alpha 1-PI and ECM
      components can be visualized by SDS-PAGE under nonreducing conditions but
      disappear upon reduction. Approximately 50% of the total alpha 1-PI bound
      covalently or noncovalently to ECM retains the ability to inhibit HLE-mediated
      ECM proteolysis. alpha 1-PI-HLE complexes bound to ECM can be visualized by SDS
      PAGE following the addition of HLE to ECM that was pretreated with [125I]alpha 1
      PI. alpha 1-PI from normal plasma or serum also binds to ECM with retention of
      immunoreactivity and partial retention of inhibitory activity. However, ECM
      pretreated with alpha 1-PI-deficient serum retains no HLE-inhibitory activity.

PMID- 8257599
TI  - Translocation of proteins across the endoplasmic reticulum.

PMID- 8257600
TI  - Antigen processing and intracellular traffic of antigens and MHC molecules.
AB  - Antigen processing leads to binding of antigenic peptides to major
      histocompatibility complex (MHC) molecules, and these peptide-MHC complexes are
      recognized by T cells. The class I and class II MHC antigen processing pathways
      employ different mechanisms and patterns of intracellular transport that allow
      the two classes to bind and present peptides from different subcellular
      compartments, determining the source and nature of peptides to be presented.

PMID- 8257601
TI  - Targeting and retention of Golgi membrane proteins.
AB  - Recent cloning of genes encoding membrane proteins of the Golgi complex has
      allowed investigation of protein targeting to this organelle. Targeting signals
      have been identified in three glycosyltransferases, a viral envelope protein and
      several proteins of the trans-Golgi network. Interestingly, the targeting signals
      for membrane proteins of the Golgi stacks seem to be contained in transmembrane
      domains. Information in the cytoplasmic tails is required for the targeting of
      trans-Golgi network proteins. Mechanisms involving both retention and retrieval
      have been invoked.

PMID- 8257602
TI  - Rab GTPases in vesicular transport.
AB  - Specificity and directionality are two features shared by the numerous steps of
      membrane transport that connect cellular organelles. By shuttling between
      specific membrane compartments and the cytoplasm, small GTPases of the Rab family
      appear to regulate membrane traffic in a cyclical manner. The restriction of
      certain Rab proteins to differentiated cell types supports a role for these
      GTPases in defining the specificity of membrane trafficking.

PMID- 8257603
TI  - Biochemical requirements for the formation of clathrin- and COP-coated transport
      vesicles.
AB  - Clathrin-coated vesicles and COP-coated vesicles constitute two major classes of
      functionally and structurally distinct transport vesicles. Cell-free assays that
      directly measure the formation of either class of vesicle are revealing important
      similarities and differences in the biochemical requirements for transport
      vesicle formation.

PMID- 8257604
TI  - Biogenesis of constitutive secretory vesicles, secretory granules and synaptic
      vesicles.
AB  - The formation of constitutive secretory vesicles and secretory granules from the
      trans-Golgi network is inhibited by brefeldin A, suggesting a role for ADP
      ribosylation factor and other coat proteins in the budding process, and is
      regulated by multiple heterotrimeric G proteins. Membrane proteins are sorted to
      secretory granules through signals in their cytoplasmic domains and, like
      secretory proteins, by aggregation of their lumenal domains. Synaptic vesicle
      membrane proteins undergo exocytotic-endocytotic recycling before synapse
      formation, consistent with the proposed biogenesis of synaptic vesicles from
      early endosomes.

PMID- 8257605
TI  - Protein sorting in the endomembrane system of plant cells.
AB  - Although many properties of the targeting of plant endomembrane proteins are
      similar to mammalian and yeast systems, several clear differences are found that
      will be stressed in this review. In the past year, significant advances in our
      understanding of storage protein segregation in the endoplasmic reticulum,
      compartmentation of Golgi, and the signals for vacuolar protein targeting have
      been made. This work will form the basis for determining the mechanism of these
      sorting phenomena.

PMID- 8257606
TI  - Genetic and biochemical studies of protein sorting to the yeast vacuole.
AB  - Studies of vacuolar protein sorting in yeast are revealing important new insights
      into the mechanisms of intracellular membrane trafficking. Recent work has raised
      questions about the prevailing view concerning membrane protein transport to the
      vacuole, and has indicated roles in vacuolar protein sorting for GTP-binding
      proteins, clathrin, a serine/threonine protein kinase and a phosphatidylinositol
      3-kinase.

PMID- 8257607
TI  - Microfilaments and membranes.
AB  - Microfilaments are intimately involved in many plasma and internal membrane
      functions. Recent studies of microfilament-membrane linking proteins and non
      filamentous myosins implicate microfilaments in diverse functions, including
      transmembrane signaling and vesicular transport. Evidence from animal and yeast
      cells suggests that microfilaments are regulated by protein phosphosphorylation,
      small GTP-binding proteins and associations involving SH3 domains.

PMID- 8257608
TI  - Transport and sorting of membrane lipids.
AB  - The lipid composition of cellular membranes may seem unnecessarily complex.
      However, the lipid composition of each membrane is carefully regulated by local
      metabolism and specificity in transport, marking the functional significance for
      the cell. Recent research has revealed unexpected discoveries concerning the
      topology of lipid synthesis, specificity in lipid transport, and the function of
      lipid and protein microdomains in sorting.

PMID- 8257609
TI  - Protein import into mitochondria: a paradigm for the translocation of
      polypeptides across membranes.
AB  - The translocation of proteins across membranes usually requires specific
      transport systems composed of membrane-bound and soluble components. A
      combination of biochemical and genetic approaches has led to the identification
      and preliminary characterization of some of these components.

PMID- 8257610
TI  - Bacterial porins: structure and function.
AB  - Within the class of integral membrane proteins, the bacterial porins display a
      remarkable resistance to denaturants and proteases. This stability is probably
      crucial for the formation of highly ordered, three-dimensional crystals.
      Structural analysis of these crystals has been possible in atomic detail. This
      analysis has revealed interesting features, such as the aromatic girdles, and has
      helped to explain several observations, including the porins' ability to
      discriminate between polar and non-polar solutes. Recent research has thus
      improved our understanding of the porins in a qualitative fashion.

PMID- 8257611
TI  - The 12-transmembrane helix transporters.
AB  - From the hydropathic profiles of their amino acid sequences many transport
      proteins are conceived to comprise 12-transmembrane alpha-helices. In only a few
      examples, however, is there genetical and/or biochemical evidence to support the
      12-helix structure or illuminate the molecular mechanism of the transport
      process. A number of these transport proteins occur in evolutionarily related
      families, and sometimes superfamilies, indicating divergent evolution of the 12
      helix structure. Other individual members or families of transport proteins are
      sufficiently different in amino acid sequence for their evolution to have taken
      place by convergence from independent ancestral origins.

PMID- 8257612
TI  - Membranes.

PMID- 8257613
TI  - Membrane permeability.

PMID- 8257614
TI  - Cystic fibrosis carrier screening: knowledge and attitudes of prenatal care
      providers.
AB  - We are conducting a trial of population carrier screening for cystic fibrosis
      (CF), targeting pregnant and nonpregnant patients of prenatal care providers. We
      first enlisted providers by presenting a description of the trial to the
      obstetrical staffs of the five Rochester, New York, hospitals having delivery
      services. Of the 124 prenatal care providers (111 obstetricians and 13 family
      practitioners) with delivery privileges at the five hospitals, only 81 (65%)
      attended one of our presentations. Providers who attended lacked knowledge about
      CF screening and counseling and expressed divergent attitudes about prenatal
      diagnosis for carrier women having test-negative partners. Of the 79 providers
      completing an attitude questionnaire, 68 (86%) were willing to offer carrier
      screening to all their patients if educational materials, testing, and counseling
      were all provided without charge. After visiting participating physicians'
      offices to orient their staff, we reached two additional conclusions. First, in
      considering whether to offer CF carrier screening to their patients, prenatal
      care providers are less concerned about imperfect test sensitivity, false
      reassurance of those testing negative, or discrimination against those testing
      positive than about time required to answer patients' questions if they screen
      and about legal liability if they do not. Second, some providers are more
      resistant to offering screening to nonpregnant patients than to pregnant
      patients, not because they believe that the timing is less appropriate, but
      because nonpregnant patients do not routinely receive an advance mailing, have
      phlebotomy, or return for follow-up. Our experience raises concerns about the
      willingness and capability of prenatal care providers to translate advances in
      molecular medicine into prenatal screening services.

PMID- 8257615
TI  - Alcohol use before and during pregnancy. PRAMS Working Group.
AB  - A woman's excessive drinking during pregnancy can cause structural and behavioral
      abnormalities in her offspring. However, population-based data concerning
      maternal drinking behaviors are sparse. To describe drinking prevalences and
      patterns, we analyzed self-reported data from the Pregnancy Risk Assessment
      Monitoring Systems of Maine, Michigan, Oklahoma, and West Virginia. During 1988
      and 1989, 6,319 mothers were surveyed two to six months after delivery; state
      specific response rates ranged from 65.6% to 83.5%. We applied statistical
      weights to the sample from each state; thus, the results estimate state-specific
      prevalences. State-specific prevalences of drinking during the last three months
      of pregnancy were low: 6.8% to 15.1% of mothers reported light drinking (one to
      six drinks per week), 0.06% to 0.30% reported moderate drinking (seven to 13
      drinks per week), and 0.03% to 0.13% reported heavy drinking (14 or more drinks
      per week). In contrast, prevalences of drinking during the three months before
      pregnancy were much higher: the range was 31.9% to 53.8% for light drinking, 1.6%
      to 3.0% for moderate drinking, and 0.6% to 1.3% for heavy drinking. State
      specific prevalences of mothers who reported receiving prenatal counseling about
      alcohol's effects ranged from 66.3% to 75.0%. More heavy drinkers than light
      drinkers received counseling. These findings indicate that moderate and heavy
      drinking during late pregnancy is relatively rare. However, all levels of
      drinking near the time of conception are much higher, and these results suggest
      the need for research into methods of reducing drinking before pregnancy.

PMID- 8257616
TI  - Use and outcomes of a cholesterol-lowering intervention for rural elderly
      subjects.
AB  - Few studies have evaluated the efficacy of cholesterol-lowering interventions in
      a community setting and have included a control or comparison group. As part of a
      preventive health demonstration project in rural Pennsylvania, Medicare
      beneficiaries underwent cholesterol screening to identify high-risk individuals
      with serum cholesterol levels > or = 240 mg/dL. These high-risk individuals were
      randomized to a cholesterol-lowering intervention through either local hospitals
      or physicians' offices or to a control group. Baseline and follow-up serum
      cholesterol levels collected two to three years later were compared according to
      service location (hospital versus physician's office), intervention attendance,
      degree of participation, baseline heart disease history, and cholesterol-lowering
      medication use at follow-up. Serum cholesterol levels decreased between 5.7% and
      6.6% in the hospital-based and physician-based groups, as well as in a control
      group not offered the intervention. Participation rates did not differ between
      treatment groups, nor did participation affect serum cholesterol levels.
      Attendance level and heart disease history were not associated with a greater
      decrease in serum cholesterol levels. Individuals reporting cholesterol-lowering
      drug use at follow-up had significantly higher baseline serum cholesterol levels
      and a significantly greater decrease in total serum cholesterol (P < .0001) than
      those not on medication. Both nonpharmacological (diet) and pharmacological
      (drug) interventions will reduce serum cholesterol levels and heart attack risk.
      The study results suggest that, at least for older individuals, the impact of
      nonpharmacological interventions on the community is minimal. We conclude that
      only very aggressive treatment will significantly loser serum cholesterol levels
      in older individuals at risk for heart attack.

PMID- 8257617
TI  - Cholesterol-related knowledge, attitudes, and behaviors in a low-income, urban
      patient population.
AB  - To determine knowledge, attitudes, behaviors, and self-reported cholesterol
      measurement in a low-income, urban patient population, we conducted an interview
      survey of users and potential users of primary care services in a public health
      care system for low-income Harris County, Texas, residents. The response rate was
      93%, with a final sample of 547 randomly selected subjects 18 years of age and
      older, who were Hispanic (54%), black (28%), non-Hispanic white (14%), and Asian,
      Native American, or other (4%). Results indicated that 76% had heard of serum or
      blood cholesterol, and 30% reported past cholesterol measurement. Knowledge that
      dietary saturated fat can raise blood cholesterol ranged from 11% in Hispanic men
      to 51% in non-Hispanic white men and women. A lower percentage of Hispanics
      correctly answered all knowledge questions, and Hispanics reported higher-fat
      food choices than blacks and non-Hispanic whites. More than 90% of the
      respondents expressed interest in more information on diet, 60% reported that
      they read nutrition labels, and 15% said they have been trying to reduce blood
      cholesterol levels. A lower percentage of Hispanics reported previous cholesterol
      measurement than blacks or non-Hispanic whites, a difference that persisted after
      adjusting for multiple factors associated with cholesterol measurement. Older age
      (older than 50) and more physician visits in the past year also were associated
      with past cholesterol measurement. Comparisons with national surveys show that
      cholesterol knowledge and actual measurement in this low-income sample lag behind
      those of the national population. Yet, despite gaps in knowledge and cholesterol
      measurement, respondents showed positive attitudes about and interest in
      cholesterol-lowering interventions.

PMID- 8257618
TI  - Use of peer role models to increase Pap smear and mammogram screening in Mexican
      American and black women.
AB  - We evaluated the use of a community-based intervention model to increase Pap
      smear and mammogram screening in minority women. The community programs were
      based on the A Su Salud (To Your Health) model, which includes the presentation
      of positive role models in the media and positive social reinforcement by
      community volunteers. Mexican-American women 40-70 years of age in Corpus
      Christi, Texas, and black women 40-70 years of age in Galveston, Texas, were
      targeted. Role models from the target community told their personal stories about
      cancer screening through local media (television, radio, and newspapers).
      Volunteers reinforced media messages among the target audience by distributing
      newsletters. Preintervention and postintervention cross-sectional surveys among
      the target group measured relative increases in knowledge, attitude, and
      practice. Pap smear use (past two years) was not substantially improved.
      Mammogram use (past two years) increased 57% among Mexican-American women
      (prevalence rate ratio [PRR] = 1.57; 90% confidence interval [CI] = 1.19, 2.08)
      and 30% among black women (PRR = 1.30; 90% CI = 1.04, 1.63). We demonstrated the
      feasibility of implementing a peer role model intervention at the local health
      department level. The improvement in mammogram use among high-risk women is
      encouraging, but further controlled research is needed to test the effectiveness
      and cost-efficiency of this approach.

PMID- 8257619
TI  - Knowledge of AIDS transmission, risk behavior, and perceptions of risk among
      urban, low-income, African-American and Hispanic youth.
AB  - Low-income, urban, African-American and Hispanic youth have been identified as a
      group that may be at risk for the spread of human immunodeficiency virus (HIV).
      This article evaluates general knowledge of acquired immunodeficiency syndrome
      (AIDS), knowledge of routes of sexual transmission of HIV, risk behaviors related
      to sex, and perceived susceptibility to AIDS of urban low-income youth in
      Detroit. We drew data from a household probability sample of 1,435 of these
      Detroit youth. The data indicate that, with a few exceptions, general knowledge
      of AIDS and routes of sexual HIV transmission was good; there were small ethnic
      and gender differences in knowledge. However, we found substantial ethnic and
      gender differences in risk behaviors. Young African-American men reported the
      earliest initiation of sexual activity and the most partners. Young Hispanic
      women reported the latest initiation of sexual activity and the fewest partners.
      A substantial minority of the youth were concerned about becoming infected with
      HIV, and these concerns were related to risk behavior. We demonstrate from these
      data a need for interventions in this population to correct misconceptions and to
      promote use of condoms and other safer sexual behaviors.

PMID- 8257620
TI  - Preventing HIV transmission: behavior and attitudes of medical house staff in a
      high-prevalence area.
AB  - Our objective was to evaluate human immunodeficiency virus (HIV) risk-factor
      assessment and counseling behavior in 86 medical house staff and to ascertain the
      effect of question format (closed versus open) on reported physician behaviors.
      We designed a cross-sectional survey using a self-report questionnaire; we
      received 78 returns of 86 questionnaires (91% response) from one-year and three
      year medical housestaff at two general medical clinics in a university-affiliated
      Bronx municipal hospital. House staff reported assessing sexual behavior (51%)
      and intravenous drug use (81%) in new patients significantly less often than they
      assessed smoking (95%) or alcohol use (94%). Counseling to reduce the risk of HIV
      transmission among all patients occurred even less frequently (41%, all P < .05).
      Question format (closed versus open) significantly affected response rate;
      respondents to closed-format questions reported far more behaviors performed.
      Intravenous drug users (IVDUs) received more frequent advice than general clinic
      patients about reducing HIV transmission (85% versus 41%), but house staff may
      ignore sexual risks in IVDUs. Resident confidence that IVDUs would change sexual
      or drug risk behavior was equally low, 1.5 on a 4-point scale. They reported
      greater discomfort discussing sexuality than drug use (2.4 versus 1.7; 4-point
      scale, P = .003). Discomfort discussing sexuality inversely associated with
      sexual history-taking in multi-variate analysis. Greater involvement with HIV
      positive patients and fewer perceived barriers to counseling were also associated
      with more assessment or counseling about risks for HIV transmission. These
      results suggest that enhancing house staff assessment and counseling efforts to
      reduce risks for HIV transmission requires interventions that foster involvement
      with HIV positive patients, emphasize the importance of sexual transmission in
      IVDUs, facilitate competence in discussing sexual behavior, and address provider
      belief that IVDUs will not change risk behaviors. Results also demonstrate a
      significant effect of question format on reported physician behavior.

PMID- 8257621
TI  - Limitations of AIDS reporting under favorable circumstances.
AB  - To assess completeness of acquired immunodeficiency syndrome (AIDS) reporting by
      a consortium of Philadelphia physicians, we compared the consortium's patient
      data base to AIDS case reports received by the Philadelphia Department of Public
      Health (PDPH). Several circumstances favored better than ordinary reporting.
      Consortium physicians were highly motivated, specialized in the care of patients
      with human immunodeficiency virus disease, had worked with PDPH physicians for
      years, and knew beforehand about the plan to compare data bases. Of 295 patients
      in the consortium data base diagnosed with AIDS at least nine months prior to
      this study, 267 (90.5%) had been reported to the PDPH and 28 (9.5%) had not. Only
      two of the missed reports were deliberately withheld, each in response to the
      patient's request. Reporting completeness increased with the time elapsed since
      diagnosis, varied by practice from 70% to 100%, and was unrelated to patient
      demographic, insurance status, or occupational characteristics. AIDS reporting
      for patients in health care occupations (11/13 = 85% reported) was not
      significantly different from reporting for patients in other occupations (256/282
      = 91% reported). We conclude that, under conditions favorable to reporting,
      approximately 10% of AIDS patients are not reported; the only patient
      characteristic that predicts reporting is the time elapsed since diagnosis; and
      nearly all reporting failures are inadvertent.

PMID- 8257622
TI  - You, me, or us: prevention and health promotion.

PMID- 8257623
TI  - Three days ago, this woman had her gallbladder removed. A remarkable new
      procedure shortens hospital stay and speeds healing.

PMID- 8257624
TI  - Gallstone disease: current therapy.
AB  - After a decade of effort to develop a minimalist alternative to standard
      cholecystectomy as the treatment for gallstone disease, laparoscopic
      cholecystectomy (LC) has emerged as the treatment of choice. Gallstone
      dissolution and lithotripsy failed to meet the tests of applicability and
      reliability. In fact, lithotripsy was denied approval by the US Food and Drug
      Administration in 1989. LC achieves the benchmark of treatment--removal of the
      diseased gallbladder and its stones--with less pain, disability, and
      disfigurement than standard surgery. The procedure is applicable in more than 90%
      of cases, being limited primarily by the severity of inflammation and the
      surgeon's experience. During the past 3 years, the special instrumentation has
      improved and operative techniques have been standardized resulting in fewer
      complications. For these reasons, laparoscopic surgical techniques are now being
      applied to a widening array of procedures including hernia repairs, bowel
      resections, antireflux procedures, common bile duct stone removal, lymph node
      dissections, and peptide ulcer disease treatment.

PMID- 8257625
TI  - Operative cholangiography performed during laparoscopic cholecystectomy.
AB  - Operative cholangiography is an important adjunct to laparoscopic
      cholecystectomy, a recently developed surgical procedure in which cholecystectomy
      is performed through four abdominal ports under sustained pneumoperitoneum and
      the direct vision of a video laparoscope. Operative cholangiogram can effectively
      identify incidental choledocholithiasis or anatomic variation in the biliary
      system that may significantly influence the surgical approach or postoperative
      management of the patient. Unique features portrayed on operative cholangiogram
      in patients undergoing laparoscopic cholecystectomy include unusual displays of
      pneumoperitoneum, subcutaneous emphysema, visualization of the unresected
      gallbladder, and overlying surgical hardware that must remain in the operating
      field during film exposure.

PMID- 8257626
TI  - Laparoscopic cholecystectomy: intraoperative ultrasound of the extrahepatic
      biliary tree and the natural history of postoperative transabdominal ultrasound
      findings.
AB  - Laparoscopic cholecystectomy (LC) has been rapidly embraced as an alternative to
      conventional open cholecystectomy (OC). While LC is less invasive than OC, it is
      still a surgical procedure with potential complications such as retained bile
      duct stones, iatrogenic injury to the bile duct with or without bile leak,
      hemorrhage, intestinal injury, and abscess formation. This article discusses the
      feasibility of intraoperative transmural ultrasound of the extrahepatic biliary
      tree with a 6.2 French catheter-based ultrasound probe and reviews the natural
      history of postoperative changes in the liver and gallbladder bed with
      conventional transabdominal ultrasound.

PMID- 8257627
TI  - Clinical features and mechanisms of major laparoscopic biliary injury.
AB  - Laparoscopic cholecystectomy has quickly become the gold standard for the
      treatment of symptomatic cholelithiasis. With the introduction of this new
      technique has come a learning curve, with a higher than expected initial rate of
      complications. The most significant complication, as with open cholecystectomy,
      is injury to the bile duct. This article reviews the clinical features and
      mechanisms of major biliary injury in laparoscopic cholecystectomy.

PMID- 8257628
TI  - Bile duct disruption after laparoscopic cholecystectomy.
AB  - The reported prevalence of biliary tract disruption following laparoscopic
      cholecystectomy has ranged from 0% to 7% in early reports. We have reviewed the
      first 823 laparoscopic cholecystectomies performed at our institution and found
      13 symptomatic biliary complications necessitating further therapy (prevalence
      1.6%). This finding represents a decrease from the 2.7% prevalence found in our
      earlier series. The incidence of biliary complications will likely continue to
      vary depending on patient selection, operator experience, and new developments in
      laparoscopic technique. Bile duct injury and bile leaks are often difficult to
      diagnose but must be strongly considered in postoperative patients with abdominal
      pain, fever, jaundice, or continued bilious drainage from a surgical drain.
      Whereas computed tomography (CT) and sonography are sensitive in detecting
      perihepatic or free peritoneal fluid collections, they are nonspecific and
      definitive diagnosis of biliary tract injury requires hepatobiliary scintigraphy,
      endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic
      cholangiography (PTC), or percutaneous aspiration. Disruption of the biliary tree
      has commonly been treated with reoperation or percutaneous drainage. More
      recently, endoscopic management has shown encouraging results for bile leaks and
      strictures in small series.

PMID- 8257629
TI  - CT findings after uncomplicated and complicated laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy (LC) is quickly becoming the standard procedure for
      gallbladder removal. Recent studies indicate that this new procedure compares
      favorably with open cholecystectomy in mortality and overall morbidity. Imaging
      has assumed an important role in the diagnosis and management of postoperative
      complications. This report reviews the CT findings after uncomplicated LC as well
      as the spectrum of CT findings seen with various postoperative complications.

PMID- 8257630
TI  - Cholescintigraphy in the diagnosis of the complications of laparoscopic
      cholecystectomy.
AB  - Cholescintigraphy has been used to diagnose postoperative bile leaks and
      obstructions after open cholecystectomy. This imaging technique has been found to
      be sensitive for detecting bile leaks that arise from cholecystectomy and defects
      in the filling and emptying of bile ducts. These observations can be applied to
      patients who are suspected of having bile duct injury after laparoscopic
      cholecystectomy. Cholescintigraphy can detect a variety of bile leaks including
      those arising from the gallbladder fossa, cystic duct, and the common bile duct.
      In addition, cholescintigraphy can be used for management of patients after
      stenting or bypass surgery, to assess bile flow and operative sites for any
      residual bile leaks. Postoperative bile duct obstructions can also be seen with
      cholescintigraphy. In this article we discuss a comprehensive postoperative
      strategy for the management and diagnosis of biliary defects after laparoscopic
      cholecystectomy with cholescintigraphy.

PMID- 8257631
TI  - Endoscopic repair of bile leaks after laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy has quickly eclipsed open cholecystectomy as the
      standard approach to symptomatic gallstones and acalculous biliary disease.
      Procedure-related morbidity and mortality continue to be defined, but a higher
      incidence of bile duct injuries has been reported to date using present
      technology and procedure. Key principles in the management of these problems
      include definition of the anatomy, relief of any impedance to biliary-enteric
      flow, and drainage of significant extrahepatic fluid collections. A cooperative,
      multispecialty approach involving surgeons, radiologists, and gastroenterologists
      is critical to successful outcomes. Future studies will help streamline the
      management of bile duct injuries and aid physicians in their selection of the
      best approach for each individual patient.

PMID- 8257632
TI  - Activation of the human immunodeficiency virus type 1 long terminal repeat by
      BTEB, a GC box-binding transcription factor.
AB  - BTEB, a GC box-binding transcription factor, was tested for its ability to
      activate the human immunodeficiency virus type 1 long terminal repeat (HIV-1
      LTR). An electrophoretic mobility shift assay demonstrated specific binding of
      BTEB to GC boxes of the HIV-1 LTR. When a BTEB expression vector was
      cotransfected into A3.01 cells with a fusion gene of HIV-1 LTR and
      chloramphenicol acetyltransferase (CAT) structural gene, the CAT activity was
      increased. This increase was accompanied by an increase in the content of CAT
      mRNA. Transcriptional activity of the HIV-1 LTR, stimulated by Tat, was further
      enhanced by the expression of BTEB. BTEB also activated the LTR activity in
      cooperation with phorbol 12-myristate 13-acetate. Northern blot analysis showed
      that various T cell and macrophage/monocyte cell lines expressed the BTEB mRNA to
      a level comparable with that of Sp1, another GC box-binding transcription factor.
      These results suggest that BTEB, like Sp1, is involved in transcriptional
      activation of the HIV-1 LTR.

PMID- 8257633
TI  - Human immunodeficiency virus type 2 (HIV-2) trans-activator (Tat): functional
      domains and the search for trans-dominant negative mutants.
AB  - Human immunodeficiency virus type 2 (HIV-2) trans-activator (Tat) is an important
      trans-regulator of viral gene expression. It differs from the related HIV-1 Tat
      in certain aspects of its structure and function. HIV-2 Tat is composed of 130
      amino acids versus 86 amino acids for HIV-1 Tat. Apart from certain conserved
      regions, there is little homology between the two Tats. They also differ in their
      ability to trans-activate HIV-2 and HIV-1 long terminal repeat (LTR)-directed
      gene expression. As an aid to understanding its mechanism of action, the
      functional domains important for HIV-2 Tat trans-activation of HIV-2 and HIV-1
      LTR-directed gene expression were investigated. Like HIV-1 Tat, HIV-2 Tat
      contains conserved cysteine- and arginine-rich domains important for its
      function. However, HIV-2 Tat differs from HIV-1 Tat in that about 20% of the HIV
      2 Tat at the amino terminus was not essential for its trans-activation function
      while HIV-1 Tat amino terminus is reportedly a part of its activation domain.
      Similarly, about 30% of the protein at the carboxy terminus of HIV-2 Tat was not
      essential. A domain critical for HIV-2 Tat-mediated trans-activation was located
      just upstream of the cysteine-rich domain. This segment is predicted to adopt an
      alpha-helical conformation and also contains acidic amino acid residues; thus, it
      may resemble amphipathic helix-type activation domains found in some
      transcriptional factors. A region with predicted hydrophobic alpha-helical
      character located between the cysteine- and arginine-rich domains was also
      important for HIV-2 Tat function. HIV-2 Tat mutants that were analogs of HIV-1
      Tat trans-dominant negative mutants did not display such a phenotype.

PMID- 8257634
TI  - Molecular cloning, expression, and biological characterization of an HTLV-II
      envelope glycoprotein: HIV-1 expression is permissive for HTLV-II-induced cell
      fusion.
AB  - The human T cell leukemia virus II (HTLV-II) is a type C retrovirus closely
      related to the human transforming retrovirus HTLV-I. In contrast to HTLV-I, the
      role of HTLV-II in human disease is controversial. However, HTLV-II infection has
      been documented in several cases of a clinically benign hairy cell leukemia and
      has also been suggested as a cofactor for HIV-1 disease progression. We report
      that an HTLV-II isolate (designated FLW) derived from a serum-positive white male
      can induce cell fusion and significant cytopathic effects in tissue culture. This
      HTLV-II isolate induced syncytium formation with human T and B cell lines,
      several human fibroblast cell lines, and, interestingly, HIV-1- and HIV-2
      infected cell lines. To elucidate the role in the FLW envelope in this
      phenomenon, we have cloned the envelope glycoproteins gp46 and gp21 of this
      isolate. The envelope glycoproteins expressed in the absence of the rest of the
      viral genome were sufficient to drive syncytium formation in vitro, and preserved
      the cellular tropism for syncytium formation observed with the native retroviral
      isolate. Amino acid (aa) sequence analysis demonstrated 88% overall similarity
      with other HTLV-II envelope glycoproteins. Interestingly, only cells infected by
      HIV-I, but not parental H9 cells, form syncytia with FLW env-transfected cells as
      well as with HTLV-II/FLW-infected BJAB-WH cells. Furthermore, antibodies directed
      at the CD4 receptor failed to inhibit the induction of giant cell formation,
      implying that the FLW envelope protein was responsible for driving syncytium
      formation in this system. These observations may be important for the
      understanding of the processes involved in human retroviral-mediated syncytium
      formation and may suggest a mechanism whereby HTLV-II could influence the disease
      process in individuals dually infected with HIV-1 and HTLV-II.

PMID- 8257635
TI  - A quantitative assay for trans-activation by HIV-1 Tat, using liposome-mediated
      DNA uptake and a parallel ELISA system.
AB  - A cellular assay is described in which transient high-level expression of a
      heterologous reporter gene (chloramphenicol acetyltransferase, CAT) driven by the
      HIV LTR is used to determine trans-activation in a cell line constitutively
      expressing Tat. The use of a parallel ELISA system to determine effects on
      expression of CAT and of the neomycin phosphotransferase (NPT) marker gene
      effectively eliminated sample variability caused by cumulative processing errors
      or cell culture conditions. In addition the use of cationic liposome-mediated
      transfection minimized delay between DNA treatment that initiates trans
      activation and addition of inhibitors, thereby eliminating background expression
      levels in treated samples. The assay has the potential to discriminate between
      inhibition of trans-activation and nonspecific effects such as inhibition of
      transfection and cytotoxicity. It has been adapted to a 96-well format suitable
      for high-throughput screening of natural products and synthetic chemicals.

PMID- 8257636
TI  - Neutralization of HIV-1 and inhibition of HIV-1-induced syncytia by 1,8
      naphthalimide photoactive compound.
AB  - The antiviral property of a newly designed class of 1,8-naphthalimide
      photochemical compounds was investigated. One such photoactive compound, 1,14-bis
      (N-hexyl-3'-bromo-1,8'-naphthalimide-4'-yl)-1,4,11,14- tetraazatetradecane-5,10
      dione (diED66Br), when activated to an excited state by visible light (420 nm),
      effectively neutralized the in vitro infectivity of human immunodeficiency virus
      (HIV-1). Light-activated diED66Br also inhibited syncytium formation induced by
      cells infected with HIV-1. Nonactivated diED66Br was completely ineffective. The
      neutralizing and syncytium-inhibiting doses of activated diED66Br had no effect
      on normal human peripheral blood mononuclear cells. Radioimmunoprecipitation
      analysis indicated that diED66Br neutralizing activity resulted primarily from
      its ability to inhibit the binding of HIV-1 envelope glycoprotein gp120 to the
      CD4 cellular receptors. Although the exact molecular mechanism of viral
      neutralization by diED66Br has not been elucidated, its ability to neutralize HIV
      1 infectivity and to inhibit syncytium formation supports further investigations
      of this photochemical as a potential therapeutic treatment of HIV-1 infection.

PMID- 8257637
TI  - The effect of age on the course of experimental feline immunodeficiency virus
      infection in cats.
AB  - Neonatal, young adult, and aged specific pathogen-free cats were experimentally
      infected with cat-passaged Petaluma strain of feline immunodeficiency virus. The
      primary stage of illness occurred 6-8 weeks following infection in cats of all
      ages, but it differed in severity and clinical signs. Generalized lymphadenopathy
      persisted for the entire 42-week study period in neonatally infected cats, was
      transient in young adults, but inapparent in aged cats. Only two aged cats became
      chronically and severely ill during the study. One aged cat died with severe
      necrotizing transmural enteritis, while a second developed chronic generalized
      staphylococcal pyoderma that was partially controlled with antibiotics.
      Neutropenia appeared 6-8 weeks following infection in cats of all ages, but was
      more severe in newborn and aged cats than in young adults. A persistent decrease
      in CD4+/CD8+ T lymphocyte ratios, due to both increased CD8+ and decreased CD4+ T
      lymphocytes, occurred in the neonatal and aged cats. Decreased CD4+/CD8+ T
      lymphocyte ratios in the young adult cats was due solely to decreased CD4+ T
      lymphocytes. Antibody response to FIV virus, as measured by ELISA to recombinant
      FIV p24 antigen, was lower in aged cats than the other age groups during the
      first 6 weeks after infection. Antibody levels were not significantly different
      among the three age groups thereafter. Although there are some differences
      between FIV infection of cats and HIV infection of human beings, age at infection
      influences the severity of disease in both species.

PMID- 8257638
TI  - Dynamics of maternal IgG antibody decay and HIV-specific antibody synthesis in
      infants born to seropositive mothers. The NYC Perinatal HIV Transmission Study
      Group.
AB  - We have used a human immunodeficiency virus type 1 (HIV-1)-specific IgG-Fc
      capture enzyme immunoassay (IgG-CEIA) to elucidate the dynamics of HIV-1 maternal
      antibody decay and de novo synthesis of HIV-1 antibodies in infants. Two hundred
      and thirty-nine serum specimens from 77 infants were analyzed by the IgG-CEIA and
      by two different conventional EIAs. With the IgG-CEIA, IgG was captured by an
      anti-human IgG monoclonal antibody (3C8) that reacts with all subclasses and was
      detected by recombinant HIV-1 envelope protein (CBre3)-peroxidase conjugate.
      Unlike the conventional EIAs, the IgG-CEIA showed a rapid decay of HIV-1-specific
      antibody in uninfected infants, with decline to background levels by 6 months
      (T1/2 [half-life] = 28-30 days). All 69 specimens collected from 39 uninfected
      infants between 6 and 15 months of age were negative by IgG-CEIA. However, HIV-1
      antibodies remained high in infected infants; 20/22 infants (90.9%) with
      specimens between the ages of 6 to 23 months were positive by IgG-CEIA.
      Subtracting mean IgG-CEIA optical density values of seroreverting infants from
      those of HIV-1-infected infants in corresponding age groups provided a model for
      seroconversion in infected infants, with detectable IgG antibody synthesis
      starting about 3 months after birth. The IgG-CEIA may be a simple and important
      tool for early diagnosis of HIV-1 infection in infants at 6 months of age.

PMID- 8257639
TI  - A new subtype of HIV-1 gag sequence detected in Taiwan.

PMID- 8257640
TI  - Confidentiality--at any price?
AB  - Confidentiality is a well respected and integral part of medical and dental
      practice and not without good reason. So fundamental is it to medicine in all its
      aspects, and so entrenched in the attitudes of those of us in the health care
      field, that it is never questioned. All patients are individuals in their own
      right and treated as such in strict confidence.

PMID- 8257641
TI  - Toothfriendly.

PMID- 8257642
TI  - Funding for dental schools.

PMID- 8257643
TI  - 'Patients' views of oral day surgery'.

PMID- 8257644
TI  - Rubber dam in general dental practice.

PMID- 8257645
TI  - The release, absorption and possible health effects of mercury from dental
      amalgam: a review of recent findings.
AB  - Recently many articles have appeared on the subject of mercury from dental
      amalgam and some of these have questioned its safety as a dental material. This
      article reviews critically the evidence on mercury release from dental amalgam
      restorations, its absorption, accumulation and excretion by the body, and its
      possible relationship to ill-effects. Finally, brief recommendations are given
      for the handling and usage of dental amalgam.

PMID- 8257646
TI  - Bonded amalgam restorations: a comparative study of glass-ionomer and resin
      adhesives.
AB  - This study assessed the effectiveness of a glass-ionomer liner/base (Vitrebond)
      and two adhesive resins (Amalgambond and Panavia Ex) in bonding amalgam to
      enamel/dentine cavities in vitro. Restorations placed without any intermediary,
      or with varnish, served for comparison purposes. Standardised unretentive
      cavities on the buccal sides of a total of 78 extracted human molar teeth were
      prepared to receive the restorations. After application of the adhesive materials
      (without light curing the Vitrebond), the cavities were filled with amalgam
      (Dispersalloy). Each specimen was stored for 24 hours in distilled water at 37
      degrees C. The amalgam restorations were then pulled from the cavities using an
      Instron machine and the retentive strength values were recorded. The results
      showed that any of the three adhesive intermediary agents substantially enhanced
      the retention of the amalgam restorations. The Vitrebond specimens had the
      highest mean retentive strength value (133 N), followed by Amalgambond (18%
      lower) and Panavia Ex (38% lower); the difference between the value for the
      Vitrebond specimens and that for the Panavia Ex specimens was statistically
      significant. The Vitrebond specimens failed due to gross enamel fractures and a
      cohesive failure of the glass-ionomer layer. The Amalgambond specimens failed at
      the resin/amalgam interface, while the Panavia Ex specimens showed enamel
      fractures and failure at the resin/dentine interface. It appears that Vitrebond
      has the potential for being an effective amalgam adhesive in vivo.

PMID- 8257647
TI  - The voluntary reflux phenomenon.
AB  - Dental erosion can be caused by recurrent contact with regurgitated gastric acid
      and there are a number of recognised conditions in which this can occur. A
      previously undescribed condition, which we have termed the 'voluntary reflux
      phenomenon', is described, and an illustrative case history given, together with
      details of several other similar cases. The condition may well be first
      recognised by the dentist, may have serious psychiatric implications, and has
      features which can help distinguish it from other causes of gastric acid mediated
      dental erosion. These features are described and discussed, and some suggestions
      for initial management in general practice made, should the condition be
      suspected.

PMID- 8257648
TI  - Multi-focal oral non-Hodgkin's lymphoma in an AIDS patient.
AB  - Cases of non-Hodgkin's lymphoma (NHL) occurring in immunosuppressed patients,
      including those who are infected with the human immunodeficiency virus, may
      develop in areas other than the lymph nodes. In AIDS-associated NHL, about 5% of
      cases of extranodal NHL are intra-oral. This case report describes the
      presentation of malignant non-Hodgkin's lymphoma in the mouth of a man who had
      AIDS. The lesion arose on separate occasions at three distinct sites,
      spontaneously regressing at each site prior to appearing at another intra-oral
      site.

PMID- 8257649
TI  - An unusual cause of burning mouth sensation.
AB  - A case of burning mouth and disturbed taste following accidental exposure to
      pyrethroid in an insecticide is reported. The symptoms were more prolonged than
      have been previously reported following cutaneous exposure.

PMID- 8257650
TI  - Can HIV be transmitted from dental personnel to patients by dentistry?
AB  - Over 19,000 patients treated by 57 HIV-infected health care workers (HCWs) have
      been tested for HIV. Apart from the notorious Florida dental case, no patient has
      been shown to be infected by treatment given by an HIV-infected HCW. Cases of 10
      HIV-infected HCWs have been examined in some depth. The evidence indicates that
      HIV transmission from HCWs to patient is exceedingly improbable, and almost
      impossible where recommended infection control procedures are adhered to.

PMID- 8257651
TI  - Transmission of HIV in a dental practice--the facts.
AB  - There is compelling evidence that six patients of a Florida dentist were infected
      with HIV at the dental practice. The strain of HIV in the dentist and patients
      was virtually identical. There is no evidence that either lapses in infection
      control or deliberate attempts to infect patients were responsible for this
      cluster of cases. Recent media analyses have emphasised that handpieces should be
      taken seriously as a potential source of cross infection but no evidence is
      available to confirm this as the route in the Florida practice. The unusual
      circumstances leading up to the detection of this cluster suggest that there
      could be other undetected cases and clusters.

PMID- 8257652
TI  - Public convenience.

PMID- 8257653
TI  - Saliva and HIV.

PMID- 8257654
TI  - Detection, identification and characterization of bacteriocin-producing lactic
      acid bacteria from retail food products.
AB  - Forty bacteriocin-producing (Bac+) lactic acid bacteria (LAB) were isolated from
      food samples purchased from retail supermarkets and local farms. Of the 40 Bac+
      isolates, 18 were isolated from 85 food samples by enrichment (21% isolation
      rate) whereas eight were obtained from 63 samples by direct plating (13%
      isolation rate). By direct plating, Bac+ LAB were detected at levels up to 2.4 x
      10(5) cfu/g in ready-to-eat meats. The Bac+ isolates were identified by
      carbohydrate fermentation patterns, SDS-PAGE protein patterns, and other
      biochemical characteristics; SDS-PAGE proved invaluable in identifying strains
      that could not be identified by other means. Differential inhibitory spectra
      against indicator microorganisms assisted in the identification of 19 unique Bac+
      isolates. Bac+ LAB included Enterococcus faecalis, Lactobacillus curvatus, Lb.
      delbrueckii, Lb. plantarum, Lactococcus lactis, and Pediococcus acidilactici. Lb.
      curvatus (four strains) and Lc. lactis (nine strains) were the only isolates
      inhibitory to foodborne pathogens including Listeria monocytogenes, Bacillus
      cereus, Clostridium perfringens and Staphylococcus aureus. Some Lc. lactis
      isolates inhibited as many as nine Gram-positive genera. Lb. curvatus FS47 and
      FS65 grew to high cell densities and produced bacteriocin at 6 degrees C;
      however, Lc. lactis FS56 produced greater levels of bacteriocin at lower cell
      densities. The high incidence of Bac+ LAB detected in retail foods indicates that
      the public is consuming a wide variety of Bac+ LAB that occur as natural
      contaminants. These data suggest a greater role for bacteriocins as
      biopreservatives in food.

PMID- 8257655
TI  - Interactive behavior of Saccharomyces cerevisiae, Bacillus pumilus and
      Propionibacterium freudenreichii subsp. shermanii.
AB  - Prevention of ropy bread caused by mucoid variants of certain bacilli presents a
      major problem for developing countries where cost of preservatives is
      prohibitive. Control of ropiness may be achieved by using propionic acid
      producing bacteria in mixed culture with leavening yeasts. Therefore, interaction
      studies between Propionibacterium freudenreichii subsp. shermanii, Bacillus
      pumilus and Saccharomyces cerevisiae were conducted in a chemically defined
      medium to test the relevance of such an approach. Growth of vegetative cells and
      germination of spores of B. pumilus were inhibited in media preincubated with P.
      shermanii at 30 degrees C for 13 h. Inhibition was bacteriostatic for the first 6
      h of incubation, becoming bactericidal between 6 and 12 h. Inhibition of B.
      pumilus spore germination was greater than inhibition of growth of vegetative
      cells of the bacterium. Culturing of either P. shermanii with S. cerevisiae or B.
      pumilus with S. cerevisiae did not produce inhibitory effects on any of the
      organisms. Inhibition of B. pumilus by P. shermanii may be useful for prevention
      of ropiness in bread prepared by the sponge method, involving fermentation of a
      portion of the dough.

PMID- 8257656
TI  - The effects of diacetate with nitrite, lactate, or pediocin on the viability of
      Listeria monocytogenes in turkey slurries.
AB  - The antilisterial effects of sodium diacetate (0.1, 0.3 and 0.5%) alone or in
      combination with sodium nitrite (30 ppm), sodium lactate (2.5%) or pediocin (5000
      arbitrary units/ml) were evaluated in slurries (25% meat in sterile deionized
      H2O) prepared from vacuum-packaged, ready-to-eat turkey breast meat and
      challenged with Listeria monocytogenes. In the absence of food additives, counts
      of L. monocytogenes increased from 4.5 log10 cfu/ml to ca. 8 log10 cfu/ml within
      1 day at 25 degrees C and within 14 days at 4 degrees C. Similarly, the pathogen
      grew to ca. 8 log10 cfu/ml within 1 d at 25 degrees C and within 28 days at 4
      degrees C in slurries containing nitrite or lactate. In the presence of pediocin,
      after an initial decrease of 0.9 log10 cfu/ml, numbers of the pathogen reached
      ca. 8 log10 cfu/ml within 5 days at 25 degrees C and within 28 days at 4 degrees
      C. However, 0.3 and 0.5% diacetate in turkey slurries were listericidal at 4 and
      25 degree C, respectively. In the presence of nitrite with diacetate, there was
      no appreciable difference in growth of L. monocytogenes compared with diacetate
      alone. Antilisterial activity was potentiated in treatments containing lactate
      with 0.3% diacetate at 25 degrees C and lactate with 0.1% diacetate at 4 degrees
      C, compared to similar treatments containing diacetate or lactate alone. A
      listericidal effect (ca. 7 log10 cfu/ml difference compared to slurries without
      additives) was observed in treatments containing pediocin with 0.5% diacetate at
      25 degrees C and pediocin with 0.3% diacetate at 4 degrees C. The pH of slurries
      containing 0.3 or 0.5% diacetate was 5.5 and 5.2, respectively, whereas nitrite
      (pH 6.2), lactate (pH 6.3) or pediocin (pH 6.2) in slurries had a negligible
      effect on pH compared to the control (pH 6.2). The increased antilisterial
      activity in slurries with diacetate in combination with other additives was due
      to synergistic effects and not just pH. Thus, sodium diacetate alone can be used
      to delay growth of L. monocytogenes in turkey, and an additional level of safety
      can be achieved using diacetate in combination with sodium lactate or pediocin.

PMID- 8257657
TI  - Spoilage and shelf-life of cod fillets packed in vacuum or modified atmospheres.
AB  - Microbial growth, sensory and chemical changes and composition of gas atmosphere
      were studied in vacuum packed (VP) and modified atmosphere packed (MAP) cod
      fillets stored at 0 degree C. Contrary to previous studies, coccobacilli and
      pleomorphic Gram-negative microorganisms (2-4 by 2-5 microns) and not Shewanella
      putrefaciens were found most likely to be the main spoilage organisms. These
      microorganisms, which may be Photobacterium phosphoreum, can explain the short
      shelf-life extension of VP and MAP fish products compared to meat products. It is
      suggested that they may inhibit the typical H2S-producing fish spoilage bacteria,
      S. putrefaciens, as the maximum concentration of H2S-producing bacteria found in
      MAP fish products is very low. Compared to VP, a shelf-life extension of 6-7 days
      was obtained with 48% CO2 in MAP. However, with pure CO2 the shelf life was only
      extended by 2-3 days. Poor texture and high drip loss indicated that the shelf
      life of these fillets was limited by chemical reactions and not only by microbial
      activity.

PMID- 8257658
TI  - Temporal frequency responsivity shows multiple maturational phases: state
      dependent visual evoked potential luminance flicker fusion from birth to 9
      months.
AB  - Maturation of temporal resolution was investigated in a visual evoked potential
      study in 77 infants from birth to 9 months of age. Luminance evoked potential
      measures in response to homogeneous sinusoidal flickering light (1-64 Hz) were
      recorded under behavioral state-defined conditions. Behavioral state was
      determined by direct observation and by polygraphic recording of the
      electroencephalogram (EEG), eye movements (EOG), muscle activity (EMG), heart
      rate (ECG), and respiration. Temporal-frequency functions of the amplitude of the
      fundamental response across the temporal-frequency range were recorded during
      sleep and wakefulness. The highest temporal-frequency response recorded during
      wakefulness was accepted as a measure for inclusion in a growth function of
      temporal-frequency responsiveness. The resulting temporal resolution frequency
      vs. age function showed three separate maturational phases. Maturational phases
      were defined as (1) an initial slow phase from 1-32 days postnatal during which
      maturation of temporal vision is unremarkable; (2) an intermediate rapid phase of
      improvement from age 26 to 170 days; and (3) an overlapping but final slow phase
      from 151 to at least 270 days during which adult-like flicker resolution is
      approximated. This study suggests that the multiple maturational phases of the
      infant's responses to flickering light are due to maturational differences, which
      correspond with maturation of structural factors of brain function. Finally,
      across the age span tested, high-frequency responsivity was influenced
      significantly by the degree of infant arousal.

PMID- 8257659
TI  - Direction selectivity and physiological compensation in the superior colliculus
      following removal of areas 17 and 18.
AB  - Previous studies indicate that cortical areas 17 and 18 play a prominent role in
      generating the direction selectivities of neurons in the superior colliculus of
      the cat. This hypothesis was tested by quantifying the activities of neurons in
      the superficial collicular layers in intact cats and cats which incurred ablation
      of areas 17 and 18 and part of area 19. In addition, since behavioral and
      anatomical studies suggest a functional adjustment in the superior colliculus
      following removal of inputs from areas 17, 18, and 19 in the neonatal cat, we
      included a group of neonatally lesioned cats. Computation of an index of
      directionality indicated that the majority of neurons in intact cats preferred
      movement in one direction, thus confirming reports of others. Following ablation
      of areas 17 and 18 and part of area 19 in both groups of lesioned cats, only
      modest changes in the population indices were detected when poorly responsive
      neurons were eliminated from the analyses. Based upon levels of visually evoked
      neuronal activity, our data suggest a physiological compensation by neurons in
      stratum griseum superficiale following removal of areas 17, 18, and 19 inputs. In
      the intact and neonatally operated groups, activity in stratum griseum
      superficiale is high, whereas in the adult lesioned group activity is low. In
      stratum opticum, neuronal activity was similar in all three groups of cats. These
      results show that neurons in stratum griseum superficiale undergo a physiological
      compensation following removal of immature areas 17 and 18.

PMID- 8257660
TI  - ON and OFF activity gradients in the lateral geniculate nucleus of the cat: a
      combined 14C 2-deoxyglucose and D,L-2-amino-4-phosphonobutyric acid study.
AB  - Experiments on the lateral geniculate nucleus (LGN) of the cat based on 14C 2
      deoxyglucose (2-DG) autoradiography and intraocular injections of 2-amino-4
      phosphonobutyric acid (APB) provided evidence for gradients of metabolic activity
      in the ON and OFF pathways in layer A, but only very weakly, if at all, in layer
      A1. Alert and freely moving cats were exposed to square-wave gratings over a 45
      min period after injection of the 2-DG. When one eye had been treated previously
      with APB, contralateral layer A showed a clear gradient of 2-DG label indicating
      that the remaining OFF pathway was most active ventrally in the layer and, by
      implication, that the ON pathway is normally most active dorsally. No gradient
      was apparent in layer A1 ipsilateral to the APB eye. Control experiments based on
      binocular injections of tetrodotoxin (TTX) demonstrated that no gradients were
      present in the baseline activity within the layers. Finally, monocular injections
      of TTX provided evidence for gradients of nondominant eye activity in layers A
      and A1 that were maximal near the interlaminar zone between layers A and A1 and
      declined in mirror-symmetric fashion toward the dorsal border of A and the
      ventral border of A1. Combined with earlier anatomical studies showing depth
      dependent patterns of geniculo-cortical projection, these results indicate that
      in the cat, as in several other species, the visual input to striate cortex is
      partly organized around ON and OFF pathways. In addition, the results suggest
      that a systematic variation of binocular interaction, perhaps related to ocular
      dominance, exists through the depths of the geniculate layers.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8257661
TI  - Parvalbumin immunoreactivity in the lateral geniculate nucleus of rhesus monkeys
      raised under monocular and binocular deprivation conditions.
AB  - Newborn rhesus monkeys were raised under monocular (lid suture, aphakia, aphakia
      corrected optically with contact lenses, and occlusion with opaque occluder
      lenses) and under binocular visual deprivation conditions (aphakia combined with
      occlusion or optical undercorrection of the fellow eye). Routine
      immunohistochemical methods with an antibody to the calcium-binding protein
      paravalbumin (PV) were used to examine the distribution of PV+ neurons and PV+
      processes in the LGN of these monkeys. Under all rearing conditions, we found no
      obvious difference in PV density in neurons in any lamina, although in all
      monocularly deprived and in two of the three binocularly deprived monkeys neurons
      connected to the deprived eye were of reduced size. Furthermore, PV
      immunoreactive processes in the neuropil of deprived laminae were as numerous and
      of the same morphologies as those in nondeprived laminae or as in normal
      controls. Thus, in the LGN of rhesus monkeys, the calcium-binding protein
      paravalbumin is resistant to monocular as well as binocular visual deprivation
      during the postnatal maturation process of the visual system.

PMID- 8257662
TI  - Retinal transformation at metamorphosis in the winter flounder
      (Pseudopleuronectes americanus).
AB  - Winter flounder (Pseudopleuronectes americanus) are hatched as bilaterally
      symmetric larvae which live near the ocean surface. At metamorphosis, they become
      laterally compressed, one eye migrates to the opposite side of the head, and they
      live the remainder of their lives lying on their blind side on the ocean floor.
      The present study characterizes and quantifies retinal cell distribution
      throughout the larval period and contrasts it with the adult retina. Based on
      light- and electron-microscopic analyses, retinas of larval flounder contain only
      a single cone-like photoreceptor type, arranged in a hexagonal array. In
      contrast, after metamorphosis, the adult retina has three types of
      photoreceptors: rods, single cones, and double cones. Rod photoreceptors are
      numerous in the ventral retina and decrease in density dorsad. The cone
      photoreceptor density, in contrast to rods, is higher in the dorsal retina
      decreasing ventrad. Adult cone photoreceptors are arranged in a square mosaic
      with four double cones surrounding one single cone. The differences in larval and
      adult retinal morphology reflect the distinctly different habitat each occupies.

PMID- 8257663
TI  - Photoreceptor spectral absorbance in larval and adult winter flounder
      (Pseudopleuronectes americanus).
AB  - The habitat occupied by larval winter flounder (Pseudopleuronectes americanus)
      differs considerably in light regime from that of the adult. To understand how
      the visual system has adapted to such changes, photoreceptor spectral absorbance
      was measured microspectrophotometrically in premetamorphic and postmetamorphic
      specimens of winter flounder. Before metamorphosis, larval flounder retinas
      contain only one kind of photoreceptor which is morphologically cone-like with
      peak absorbance at 519 nm. After metamorphosis, the adult retina has three types
      of photoreceptors: single cones, double cones, and rods. The visual pigment in
      single cones has a peak absorbance at lambda max = 457 nm, the double cones at
      lambda max = 531 and 547 nm, and the rod photoreceptors at lambda max = 506 nm.
      Double cones were morphologically identical, but the two members contained either
      different (531/547 nm) or identical pigments (531/531 nm). The latter type were
      found only in the dorsal retina. The measured spectral half-bandwidths (HBW) were
      typical of visual pigments with chromophores derived from vitamin A1 with the
      possible exception of the long-wavelength absorbing pigment in double cones which
      appeared slightly broader. Because the premetamorphic pigment absorbance has a
      different lambda max than those of the postmetamorphic pigments, different opsin
      genes must be expressed before and after metamorphosis.

PMID- 8257664
TI  - Pharmacological separation of mechanisms contributing to human contrast
      sensitivity.
AB  - Two basic types of cholinergic receptor have been identified in nervous systems:
      nicotinic and muscarinic. In the mammalian visual system, the balance of evidence
      suggests that nicotinic activity is associated primarily with transmission and
      processing of information while muscarinic activity reflects modulatory
      influences arising in the brainstem and basal forebrain. We have measured
      contrast sensitivity functions using a two-alternative forced-choice procedure in
      young human volunteers with and without administration of nicotine (1.5 mg by
      buccal absorption) or the muscarinic antagonist scopolamine (1.2 mg orally).
      Scopolamine elevates contrast-detection thresholds uniformly at all spatial
      frequencies, consistent with blocking of a nonspecific arousal system. Nicotine,
      in contrast, improves sensitivity at low spatial frequencies (below about 4
      cycle/deg); at higher spatial frequencies sensitivity is, if anything, impaired.
      Using counterphase gratings, we find that scopolamine elevates thresholds
      uniformly at all temporal frequencies. Nicotine lowers thresholds at high but not
      low temporal frequencies. The results obtained with nicotine suggest that
      contrast sensitivity reflects the activity of two mechanisms, or sets of
      spatiotemporal filters, that are pharmacologically distinct, the contrast
      sensitivity function reflecting the envelope of their sensitivities.

PMID- 8257665
TI  - Morphology of a small-field bistratified ganglion cell type in the macaque and
      human retina.
AB  - In in-vitro preparations of both macaque and human retina, intracellular
      injections of Neurobiotin and horseradish peroxidase were used to characterize
      the morphology, depth of stratification, and mosaic organization of a type of
      bistratified ganglion cell. This cell type, here called the small bistratified
      cell, has been shown to project to the parvocellular layers of the dorsal lateral
      geniculate nucleus (Rodieck, 1991) and is therefore likely to show color-opponent
      response properties. In both human and macaque, the two dendritic tiers of the
      bistratified cell are narrowly stratified close to the inner and outer borders of
      the inner plexiform layer. The inner tier is larger in diameter and more densely
      branched than the outer tier and gives rise to distinct spine-like branchlets
      bearing large, often lobulated heads. By contrast the smaller, outer tier is
      sparsely branched and relatively spine-free. In human retina, the small
      bistratified cells range in dendritic field diameter from approximately 50
      microns in central retina to approximately 400 microns in the far periphery. The
      human small bistratified cells are about 20% larger in dendritic-field diameter
      than their counterparts in the macaque. However, when the difference in retinal
      magnification between human and macaque is taken into account, the small
      bistratified cells are similar in size in both species. In macaque, the small
      bistratified cell has a dendritic-field size that is approximately 10% larger
      than that of the magnocellular-projecting parasol ganglion cell. Human small
      bistratified ganglion cells tend to have smaller dendritic-field diameters than
      parasol cells. This is because parasol ganglion cells are larger in human than in
      macaque retina (Dacey & Petersen, 1992). In macaque retina, intracellular
      injections of Neurobiotin revealed heterotypic tracer coupling to a distinct
      mosaic of amacrine cells and probable homotypic coupling to an array of
      neighboring ganglion cells around the perimeter of the injected cell's dendritic
      tree. The amacrine cell mosaic had a density of 1700 cells/mm2 in peripheral
      retina. Individual amacrines had small, densely branched and bistratified
      dendritic fields. From the homotypic coupling, it was possible to estimate for
      the small bistratified cell a coverage factor of approximately 1.8, and a density
      of approximately 1% of the total ganglion cells in central retina, increasing to
      approximately 6-10% in the retinal periphery. The estimated density, dendritic
      field size, and depth of stratification all suggest that the small bistratified
      ganglion cell type is the morphological counterpart of the common short
      wavelength sensitive or 'blue-ON' physiological type.

PMID- 8257666
TI  - Color-reversal learning: effects after lesions of thalamic visual structures in
      pigeons.
AB  - The performance of pigeons on a color-reversal learning task was assessed after
      thalamic lesions disrupting the thalamofugal and tectofugal visual pathways.
      Successful performance of a simultaneous color discrimination was accomplished
      after surgery, and a series of reversals of the original discrimination followed
      during which the positive and negative consequences associated with the stimuli
      were interchanged. Shimizu and Hodos (1989) had reported that lesions of two
      laminae in the visual wulst (IHA and HD), both targets of the avian thalamofugal
      pathway, resulted in increased errors in a color-reversal learning task in
      pigeons. This finding suggested that the thalamofugal pathway might play a role
      in visual discrimination involving stimulus context changes. In the present
      study, lesions of the OPT complex (the thalamic source of afferents to IHA and
      HD) were found to have no effect on color-reversal learning performance. Instead,
      we found that damage to nucleus rotundus (the thalamic component of the
      tectofugal pathway) resulted in deficits that were far in excess of those that
      had been obtained after IHA and HD lesions. We suggest that the color-reversal
      learning deficits after Wulst lesions are not due to the Wulst's connections with
      the thalamofugal pathway, but rather to its connections with the tectofugal
      pathway.

PMID- 8257667
TI  - Neurochemical compartmentation of monkey and human visual cortex: similarities
      and variations in calbindin immunoreactivity across species.
AB  - The compartmental organization of visual cortical neurons was examined across
      species of primates by directly comparing the pattern of immunoreactivity for the
      28-kD vitamin D-dependent calcium-binding protein (calbindin) in area 17 of
      squirrel monkeys, macaques, and neurologically normal adult humans. Area 17 of
      macaques and squirrel monkeys was similar in that somata and processes intensely
      immunoreactive for calbindin were present in the same layers (II-III, IVB, and V)
      and in both species formed a well-stained matrix that surrounded the CO-rich
      puffs in layer III. These intensely calbindin-immunoreactive neurons were
      identified as subpopulations of GABA-immunoreactive neurons. Among the most
      obvious differences in the two monkey species was the distribution of calbindin
      positive elements outside of layer III: a dense immunostained matrix surrounded
      the puffs in layers II, IVB, V, and VI of squirrel monkeys but the immunostained
      neurons adopted no regular pattern outside layer III in macaques. In addition,
      although somata lightly immunoreactive for calbindin were present in both
      species, they were much more abundant in squirrel monkeys than macaques. The
      pattern of calbindin immunostaining in human area 17 resembled that of macaques
      in forming an intense matrix that surrounded puffs only in layer III, yet also
      resembled that of squirrel monkeys by including large numbers of light
      immunoreactive somata. These lightly immunostained somata included a very dense
      population forming a prominent band in layer IVA of human visual cortex. We
      conclude that for layer III of primary visual cortex, a similar pattern of
      neuronal chemistry exists across species of primates which is related to this
      layer's compartmental organization. Yet for other layers, the expression of
      calbindin immunoreactivity varies from one species to the next, perhaps
      reflecting variations in other neuronal properties.

PMID- 8257668
TI  - Contrast adaptation in striate cortical neurons of the nocturnal primate bush
      baby (Galago crassicaudatus).
AB  - It has been argued that in order for the visual system to detect edges accurately
      under a range of conditions, the visual system needs to adapt to the local
      contrast level to preserve sensitivity (Blakemore & Campbell, 1969). Cells in the
      primary visual cortex of cats adapt to stimuli with low to moderate contrast.
      Curiously, macaque monkey neurons in primary visual cortex (V1) do not show
      evidence for similar adaptation. To address the question of whether this
      differential sensitivity in contrast adaptation might be due to phylogenetic
      variation between cats and primates or to specializations for visual niche (e.g.
      nocturnal vs. diurnal), contrast adaptation to temporally and spatially optimized
      gratings was examined in 30 V1 cells of three nocturnal primate bush babies
      (Galago crassicaudatus). A second objective was to examine the relationship
      between the degree of contrast adaptation and cell classification or cell
      location relative to cortical layers or compartments [i.e. cytochrome-oxidase
      (CO) blobs and interblobs]. All cells were classified (simple vs. complex) and
      anatomically localized relative to cortical layers and cytochrome-oxidase (CO)
      blob and interblob compartments. Two independent measures of contrast adaptation
      were used. In the first test, contrast was sequentially increased from 3-56% and
      then decreased. The contrast required to maintain a half-maximum response
      amplitude in the 30 cells tested increased an average of 0.24 (+/- 0.12) log
      units during the sequential decrements in contrast. For the second test, four
      sets of five interleaved contrasts within +/- 1 octave of a central adapting
      contrast (10%, 14%, 20%, and 28%, respectively) were presented. The cells
      produced a mean adaptation index of 0.57 (+/- 0.47) which is very similar to that
      exhibited by cat cortical neurons (0.54 +/- 0.41). Interestingly, cells in
      interblobs showed a trend toward greater adaptation than did blob cells.
      Moreover, cells in the supragranular layers exhibited greater adaptation than
      cells in the infragranular layers. No significant differences in adaptation were
      found to correlate with other cell classification indices. Taken together, our
      results suggest that contrast adaptation may be more important for maintaining
      sensitivity in nocturnal species (primates or cats) than in diurnal species
      (macaque monkeys), and that in the nocturnal bush baby, cells in cortical layers
      and compartments may be differentially specialized for contrast adaptation.

PMID- 8257669
TI  - Spatial summation in blindsight.
AB  - Spatial summation curves were determined in the circumscribed visual-field
      defects of five patients with blindsight. Under light-adapted conditions that
      favor the color-opponent system, increment thresholds for white and red targets
      presented on a white background were measured as a function of stimulus size
      which ranged from 9-110 min arc. In both normal and defective hemifields,
      summation was linear for the red stimuli. In contrast, the curves measured with
      the white stimuli showed some nonlinearity in the normal hemifield, and a
      pronounced eccentricity-dependent notch in the field defect. The results indicate
      that the neurons mediating sensitivity differ in their summation properties for
      wavelength and intensity information.

PMID- 8257670
TI  - Excitation and inhibition in orientation selectivity of cat visual cortex neurons
      revealed by whole-cell recordings in vivo.
AB  - One striking transformation in response properties that occurs in the geniculo
      cortical pathway is the appearance of a high degree of orientation selectivity in
      the cortex. This property may be conceived as arising purely from the excitatory
      inputs to the cell, as being structured largely by the inhibition a cortical cell
      receives or could be due to a combination of the two. We have studied the
      contributions of excitatory and inhibitory inputs to cortical cells' orientation
      selectivity by analyzing the postsynaptic potentials evoked in cat striate
      neurones by flashing stimuli of different orientations. We made these recordings
      using the in vivo whole-cell technique (Xing Pei et al., 1991), which provides
      more stable and reliable results than classical intracellular recording methods.
      Our results show that the cat striate cortex exhibits a variety of mechanisms to
      achieve orientation selectivity. Orientation selectivity of a particular cell can
      be created by excitatory, by inhibitory, or by a combination of both mechanisms.

PMID- 8257671
TI  - Responses of neurons in macaque MT to stochastic motion signals.
AB  - Dynamic random-dot stimuli have been widely used to explore central mechanisms of
      motion processing. We have measured the responses of neurons in area MT of the
      alert monkey while we varied the strength and direction of the motion signal in
      such displays. The strength of motion is controlled by the proportion of
      spatiotemporally correlated dots, which we term the correlation of the stimulus.
      For many MT cells, responses varied approximately linearly with stimulus
      correlation. When they occurred, nonlinearities were equally likely to be either
      positively or negatively accelerated. We also explored the relationship between
      response magnitude and response variance for these cells and found, in general
      agreement with other investigators, that this relationship conforms to a power
      law with an exponent slightly greater than 1. The variance of the cells'
      discharge is little influenced by the trial-to-trial fluctuations inherent in our
      stochastic display, and is therefore likely to be of neural origin. Linear
      responses to these stochastic motion stimuli are predicted by simple, low-level
      motion models incorporating sensors having relatively broad spatial and temporal
      frequency tuning.

PMID- 8257672
TI  - Synaptic feedback, depolarization, and color opponency in cone photoreceptors.
AB  - For some 20 years, synaptic feedback from horizontal cells to cones has often
      been invoked, more or less convincingly, in discussions of retinal action and
      vision. However, feedback in cones has proved to be rather complex and difficult
      to study experimentally. The mechanisms and consequences of feedback are
      therefore still only partly understood. This review attempts to assess the knowns
      and unknowns. The limitations of the evidence for feedback are reviewed to
      support the position that unequivocal evidence still largely rests on
      intracellular recording from cones. Of the three distinct types of depolarization
      observed in cones, the graded depolarization is taken as the fundamental
      manifestation of feedback. The evidence for the hypothesis that GABA is the
      neurotransmitter for feedback appears reasonably strong but several complications
      will have to be resolved to make the hypothesis more secure. There is evidence
      that feedback contributes to aspects of light adaptation and spatiotemporal
      processing of visual information. The contributions seem modest in magnitude. The
      role of feedback in shaping the color-opponent responses of retinal neurons is
      evaluated with particular emphasis on pharmacological studies, spatial and
      temporal aspects of the response of chromatic horizontal cells, and the enigmatic
      nature of depolarizations in blue- and green-sensitive cones. On this and other
      evidence, it is suggested that feedback may impress some detectable wavelength
      dependency in some cones but the dominant mechanisms for color opponency probably
      reside beyond the photoreceptors.

PMID- 8257673
TI  - Stimulus configuration and location in the visual field affect appetitive
      responses by the praying mantis, Sphodromantis lineola (Burr.).
AB  - Adult female praying mantises, Sphodromantis lineola (Burr.), were presented with
      computer-generated black rectangular stimuli that moved horizontally or
      vertically at 82 deg/s against a homogeneous white background. Both stimulus
      configuration (orientation in relation to direction) and the retinal location of
      the stimulus image affected the rate at which mantises responded appetitively
      (approached or struck at the stimulus). Mantises responded most to square stimuli
      (12.5 deg x 12.5 deg) when they moved horizontally or vertically through, or
      horizontally at 24.5 deg below the center of their visual field. Mantises also
      responded most to vertically (vs. horizontally) oriented rectangular stimuli
      (12.5 deg x 47 deg) that moved through their visual-field center, irrespective of
      whether the stimuli moved downward or horizontally. Upward moving stimuli
      elicited intermediate amounts of behavior with no configuration preference.
      Mantises did not demonstrate a configuration preference when rectangular stimuli
      moved > or = 24.5 deg outside of the visual-field center. Furthermore, mantises
      responded very little and demonstrated no configuration preferences to stimuli
      that moved less than approximately 83 deg through their visual field even if the
      stimuli moved through the visual-field center.

PMID- 8257674
TI  - Structure of the Mg(2+)-bound form of CheY and mechanism of phosphoryl transfer
      in bacterial chemotaxis.
AB  - The response regulator protein of bacterial chemotaxis, CheY, is representative
      of a large family of signal transduction proteins that function as
      phosphorylation-activated switches to regulate the activities of associated
      effector domains. These regulators catalyze the metal ion-dependent phosphoryl
      transfer and dephosphorylation reactions that control the effector activities.
      The crystal structures of Salmonella typhimurium CheY with and without Mg2+ bound
      at the active site have been determined and refined at 1.8-A resolution. While
      the overall structures of metal-bound and metal-free CheY are similar,
      significant rearrangements occur within the active site involving the three most
      highly conserved residues of the response regulator family. Conservation of the
      cluster of carboxylate side chains at the active site of response regulator
      domains can be rationalized in terms of their role in coordinating the
      catalytically essential divalent metal ion. The Mg2+ coordination geometry
      provides insights to the mechanism of phosphoryl transfer.

PMID- 8257675
TI  - Structure and thermodynamics of nonalternating C.G base pairs in Z-DNA: the 1.3-A
      crystal structure of the asymmetric hexanucleotide d(m5CGGGm5CG).d(m5CGCCm5CG).
AB  - We have solved the single-crystal X-ray structure of the complementary
      hexanucleotides d(m5-CGGGm5CG) and d(m5CGCCm5CG). The hexamer duplex was
      crystallized as Z-DNA, but contains a single C.G base pair that does not follow
      the alternating pyrimidine/purine rule for Z-DNA formation. This is the first
      crystal structure which serves to illustrate the structural consequences of
      placing a cytosine in the sterically disfavored syn conformation. In addition,
      since these sequences are not self-complementary, the individual strands of this
      asymmetric hexamer are unique in sequence and therefore distinguishable in the
      crystal lattice. Nevertheless, the crystal of this duplex is isomorphous with
      other Z-DNA hexamer structures. The asymmetry of this hexamer sequence required
      that the structure be solved using two unique models, which are distinguished by
      the orientation of hexanucleotides in the crystal lattice. In one model (the GG
      model) the cytosine in the syn conformation is packed against the terminal
      guanine base of a symmetry-related hexamer, while in the alternative model (the
      CC model) this cytosine sits exposed in a solvent channel of the lattice. We find
      that neither model alone can completely account for the observed electron
      densities. The two models ultimately were refined together. A composite structure
      consisting of 65% GG model and 35% CC model refined to an R-factor of 19.3%,
      which was significantly lower than refinements using either model alone. A
      detailed analysis of these two structures shows that, in spite of the out-of
      alternation C.G base pair, the features characteristic of Z-DNA have been
      maintained. Both models, however, show significant local structural adjustments
      to accommodate the single cytosine base which is forced to adopt the syn
      conformation in each hexamer. In general, it appears that in order to relieve the
      energetically unfavorable steric contacts between the cytosine base in the syn
      conformation and the deoxyribose sugar, the base is forced into a highly buckled
      conformation, and that this large buckle in turn alters the conformation of
      neighboring residues. This unusual conformation also significantly weakens base
      stacking interactions between the cytosine in syn and the adjacent residues in
      the helix and affects the exposure of the bases to solvent. We conclude that this
      crystal structure provides a molecular rationale for why nonalternating bases are
      energetically disfavored in Z-DNA.

PMID- 8257676
TI  - DNA helicase associated with DNA polymerase alpha: isolation by a modified
      immunoaffinity chromatography.
AB  - We have developed a novel immunoaffinity method for isolating a DNA polymerase
      alpha-associated DNA helicase from the yeast Saccharomyces cerevisiae. Earlier we
      have reported the characterization of a DNA helicase activity associated with the
      multiprotein DNA polymerase alpha complex from yeast [Biswas, E. E., Ewing, C.
      M., & Biswas, S. B. (1993) Biochemistry 32, 3030-3027]. We report here the
      isolation of the DNA helicase from the DNA polymerase alpha (pol alpha) complex
      bound to an anti-pol alpha immunoaffinity matrix. The DNA helicase activity
      eluted at approximately 0.35 M NaCl concentration. The eluted ATPase/helicase
      peak was further purified by size-exclusion high-performance liquid
      chromatography (HPLC). At low ionic strength (50 mM NaCl), it remained associated
      with other proteins and eluted as a large polypeptide complex. At high ionic
      strength (500 mM NaCl), the helicase dissociated, and the eluted ATPase/helicase
      fraction contained 90-, 60-, and 50-kDa polypeptides. Photoaffinity cross-linking
      of helicase with ATP during the isolation process demonstrated a 90-kDa
      polypeptide to be the likely ATP binding component of the helicase protein. The
      DNA helicase has single-stranded DNA (ssDNA)-stimulated ATPase and dATPase
      activities. The ATPase activity was stimulated by yeast replication protein A
      (RPA). The DNA helicase activity was stimulated by Escherichia coli ssDNA binding
      protein and RPA. The DNA helicase migrated on a DNA template in the 5'-->3'
      direction which is also the overall direction of migration of pol alpha on the
      lagging strand of the replication fork.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257677
TI  - Structure and dynamics of the sialic acid moiety of GM3-ganglioside at the
      surface of a magnetically oriented membrane.
AB  - 13C-NMR techniques in oriented bilayer systems composed of DMPC and CHAPSO have
      been used to measure dipolar interactions between 13C-13C and 13C-1H pairs
      located in the sialic acid moiety of ganglioside GM3. These interactions are
      reduced to a structural and motional model for the headgroup of this glycolipid
      using an order matrix approach. The analysis shows an average structure
      possessing a high degree of order and is most consistent with structures that are
      well extended from the membrane surface. Saturation of the ganglioside
      environment with high concentrations of Ca2+ (0.28 M) produces a small
      perturbation of the headgroup. GM3 dissolved in a DMPC/CHAPSO system can also be
      demonstrated to bind wheat germ agglutinin (WGA). The minimal perturbation of
      structure-dependent parameters suggests that the dominant structure of the sialic
      acid moiety in the isolated membrane system is favored for binding by the
      protein.

PMID- 8257678
TI  - Solution structure of a conserved DNA sequence from the HIV-1 genome: restrained
      molecular dynamics simulation with distance and torsion angle restraints derived
      from two-dimensional NMR spectra.
AB  - The three-dimensional solution structure of a trisdecamer DNA duplex sequence,
      d(AGCTTGCCTTGAG).d(CTCAAGGCAAGCT), from a conserved region of HIV-1 genome's long
      terminal repeat, has been investigated using NMR spectroscopy and restrained
      molecular dynamics calculations. Interproton distances derived from two
      dimensional nuclear Overhauser enhancement (2D NOE) experiments, using the
      iterative complete relaxation matrix algorithm MARDIGRAS, and torsion angles for
      sugar rings, estimated from stimulated fitting of double-quantum-filtered
      correlation (2QF-COSY) spectra, were obtained [Mujeeb, A., Kerwin, S. M., Egan,
      W. M., Kenyon, G. L., & James, T. L. (1992) Biochemistry 31, 9325-38]. These
      structural restraints have now been employed as the basis for structure
      refinement using restrained molecular dynamics (rMD) to search conformational
      space for structures consistent with the experimental restraints. Specifically,
      upper and lower bounds on the restraints were incorporated into the AMBER
      (version 4.0) total potential energy function of the system, the bounds being
      used to define the width of a flat-well penalty term in the AMBER force field.
      Confidence in the time-averaged structure obtained is engendered by convergence
      to essentially the same structure (root-mean-square deviation approximately 0.9
      A) when two quite different DNA models, A-DNA and B-DNA (RMSD approximately 6.5
      A), were employed as starting structures and when various initial trajectories
      were used for the rMD runs. The derived structure is further supported by the
      total energy calculated, the restraint violation energy, the restraint
      deviations, and the fit with experimental data. For the latter, the sixth-root
      residual index indicated a good fit of the determined structure with experimental
      2D NOE spectral intensities (R1x < 0.07), and the RMS difference between vicinal
      proton coupling constants calculated for the derived structure and experimental
      coupling constants were also in reasonable agreement (JRMS = 0.9 Hz). While the
      structure of the trisdecamer is basically in the B-DNA family, some structural
      parameters manifest interesting local variations. The helix parameters indicate
      that, compared with classical B-DNA, the structure is longitudinally more
      compressed. Local structural variations at the two TG steps in particular
      together create bending into the major groove of the duplex. Comparison of the
      two-CTTG-tetrads in the duplex reveals that they have similar structures, with
      the TT moieties being almost identical; however, the -CTTG-pur sequence has a
      larger roll and slide for the -TG- step than for the -CTTG-pyr sequence, in
      accord with published X-ray crystallographic conclusions.

PMID- 8257679
TI  - NMR solution structure and flexibility of a peptide antigen representing the
      receptor binding domain of Pseudomonas aeruginosa.
AB  - A synthetic peptide antigen corresponding to the C-terminus of Pseudomonas
      aeruginosa K strain pilin has been studied by one and two-dimensional NMR
      techniques. This peptide exists in two isomeric forms which arise as a result of
      the I138-P139 amide bond. An ensemble of solution conformations for the trans
      form of this 17-residue disulfide-bridged peptide (PAK 128-144) has been
      generated using a simulated annealing procedure in conjunction with distance and
      torsion angle restraints derived from NMR data. One major class of backbone
      conformations has been identified for this potential synthetic vaccine and
      indicates the presence of two beta-turns in the region 134-142. The region that
      has been established as the epitope for the monoclonal antibody PK99H is
      consistent with the region of the major conformers that exhibit the most
      definition in the ensemble (134-140) and also includes a type I beta-turn from
      residues 134 to 137. The generated structures are also consistent with observed
      NOEs characteristic of beta-turns and amide proton temperature coefficient data,
      which indicate the presence of two turns between residues 134 and 142. The
      presence of secondary structure within the epitope substantiates the theory that
      immunogenic regions of proteins are those which contain surface-exposed
      structural elements such as beta-turns. Further implications of the structure on
      antigenicity and cross-reactivity are discussed.

PMID- 8257680
TI  - Direct observation and elucidation of the structures of aged and nonaged
      phosphorylated cholinesterases by 31P NMR spectroscopy.
AB  - 31P NMR spectroscopy of butyrylcholinesterase (BChE), acetylcholinesterase
      (AChE), and chymotrypsin (Cht) inhibited by pinacolyl methylphosphonofluoridate
      (soman), methylphosphonodifluoridate (MPDF), and diisopropyl phosphorofluoridate
      (DFP) allowed direct observation of the OP-linked moiety of aged
      (nonreactivatable) and nonaged organophosphorus (OP)-ChE conjugates. The 31P NMR
      chemical shifts of OP-ChE conjugates clearly demonstrated insertion of a P-O-
      bond into the active site of aged OP-ChE adducts. The OP moiety of nonaged OP
      ChEs was shown to be uncharged. The OP-bound pinacolyl moiety of soman-inhibited
      and aged AChE was detached completely, whereas only partial dealkylation of the
      pinacolyl group was observed for soman-inhibited BChEs. This suggests that the
      latter enzyme reacted with the less active stereoisomer(s) of soman. In the case
      of soman-inhibited Cht, no dealkylation could be experimentally detected for any
      of the four stereoisomers of OP-Cht adducts. Results are consistent with the
      contention that the phenomenon of enzyme-catalyzed dealkylation of OP adducts of
      serine hydrolases strongly depends on the orientation of both the catalytic His
      and the carboxyl side chain of either Glu or Asp positioned next to the catalytic
      Ser. The denatured protein of aged OP-ChE or OP-Cht is a convenient leaving group
      in nucleophilic displacements of tetrahedral OP compounds despite the presence of
      a P-O- bond. This indicates that the unusual resistance to reactivation of the
      aged enzyme cannot be ascribed to simple electrostatic repulsion of an
      approaching nucleophile. The broadening of the 31P NMR signal of native OP-ChEs
      relative to that of OP-Cht is in agreement with the crystal structure of AChE,
      showing that the active site region of ChEs in solution resides in a deep, narrow
      gorge.

PMID- 8257681
TI  - Refined solution structure of the glucocorticoid receptor DNA-binding domain.
AB  - A refined solution structure of the glucocorticoid receptor DNA-binding domain
      (GR DBD) has been determined using two- and three-dimensional nuclear magnetic
      resonance (NMR) spectroscopy on an 15N-labeled GR DBD fragment in conjunction
      with distance geometry and simulated annealing calculations. Thirty structures of
      the fragment C440-R510 of the rat GR were calculated based on 906 distance
      constraints obtained from NOE intensities (168 intraresidue and 738 interresidue
      NOEs) and 43 dihedral constraints. Average atomic root mean square (rms)
      differences between the 24 best structures and their geometric average are 0.70 A
      for backbone atoms and 1.44 A for all heavy atoms. Several regions that were not
      well defined in a previous NMR structure determination of a similar protein
      fragment [Hard, T., Kellenbach, E., Boelens, R., Maler, B.A., Dahlman, K.,
      Freedman, L.P., Carlstedt-Duke, J., Yamamoto, K.R., Gustafsson, J.-A., & Kaptein,
      R. (1990b) Science 249, 157-160] are now well-defined. The refined structure of
      the uncomplexed GR DBD is very similar to the crystal structure of GR DBD in a
      sequence specific DNA complex [Luisi, B. F., Xu, W. X., Otwinowski, Z., Freeman,
      L. P., Yamamoto, K. R., & Sigler, P. B. (1991) Nature 352, 497-505], in
      particular with regard to the presence and relative positions of secondary
      structure elements. The backbone atom rms difference between the average NMR
      solution structure and the crystal structure of the DNA-complexed GR DBD is 1.8
      A. The most pronounced differences between the free and DNA-complexed states are
      found within the fragment C476-C482 in the second zinc-coordinating
      domain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257682
TI  - Catalysis of acetoin formation by brewers' yeast pyruvate decarboxylase isozymes.
AB  - Catalysis of C(alpha)-proton transfer from 2-(1-hydroxyethyl)thiamin diphosphate
      (HETDP) by pyruvate decarboxylase isozymes (PDC; EC 4.1.1.1) from Saccharomyces
      carlsbergensis was investigated by determining the steady-state kinetics of the
      reaction of [1-L]acetaldehyde (L = H, D, or T) to form acetoin and the primary
      kinetic isotope effects on the reaction. The PDC isozyme mixture and alpha 4
      isozyme (alpha 4-PDC) have different steady-state kinetic parameters and isotope
      effects for acetoin formation in the presence and absence of the nonsubstrate
      allosteric effector pyruvamide: pyruvamide activation occurs by stabilization of
      the acetaldehyde/PDC ternary complex. The magnitudes of primary L(V/K)-type (L =
      D or T) isotope effects on C(alpha)-proton transfer from alpha 4-PDC-bound HETDP
      provide no evidence for significant breakdown of the Swain-Schaad relationship
      that would indicate partitioning of the putative C(alpha)-carbanion/enamine
      intermediate between HETDP and products. The substrate concentration dependence
      of the deuterium primary kinetic isotope effects provides evidence for an
      intrinsic isotope effect of 4.1 for C(alpha)-proton transfer from alpha 4-PDC
      bound HETDP. A 1.10 +/- 0.02-fold 14C isotope discrimination against [1,2
      14C]acetaldehyde in acetoin formation is inconsistent with a stepwise mechanism,
      in which the addition step occurs after rate-limiting formation of the C(alpha)
      carbanion/enamine as a discrete enzyme-bound intermediate, and provides evidence
      for a concerted reaction mechanism with an important component of carbon-carbon
      bond formation in the transition state.

PMID- 8257683
TI  - NMR investigation of isotopically labeled cyanide derivatives of lignin
      peroxidase and manganese peroxidase.
AB  - The 1H NMR spectroscopy was used to study lignin peroxidase (LiP) and manganese
      peroxidase (MnP) containing deuterated histidines. LiP and MnP were obtained from
      a histidine auxotroph of the fungus Phanerochaete chrysosporium grown in the
      presence of deuterated histidines. The derivatives with deuterated histidines
      have allowed a firm assignment of the protons of the distal and proximal
      histidines. We have also found that the LiP from this strain exhibits different
      orientations of the 2-vinyl group compared to the LiP from the strain previously
      studied. Mobility of the group has also been detected, thus explaining the
      apparent inconsistency between X-ray solid-state and NMR solution data. The 15N
      shift values of 15N-enriched CN- in the cyanide derivatives of LiP and MnP have
      also been measured. The shift patterns, both for 15N and for the proximal
      histidine protons of several peroxidases, are consistent with predominant contact
      shift contributions which reflect the bond strength of the metal-axial ligand.
      Finally, our results confirm a correlation between shift values of 15N and those
      of proximal histidine protons and the Fe3+/Fe2+ redox potentials.

PMID- 8257684
TI  - 7Li NMR relaxation study of Li+ binding in human erythrocytes.
AB  - We used 7Li NMR spin-lattice (T1) and spin-spin (T2) relaxation time measurements
      to investigate the binding of Li+ in human red blood cell (RBC) suspensions. In
      RBCs containing 1.4 mM Li+, the intracellular 7Li NMR T2 relaxation value (0.30
      +/- 0.03 s) was much smaller than the corresponding T1 value (6.0 +/- 0.1 s),
      yielding a ratio of T1 to T2 of 20. For 1.5 mM LiCl solutions whose viscosities
      were adjusted to 5 cP with glycerol, the values of the T1/T2 ratios were as
      follows: 49 for unsealed RBC membrane (2.0 mg of protein/mL); 4.4 for spectrin
      (1.9 mg/mL); 1.5 for 5.4 mM 2,3-bisphosphoglycerate (BPG); 2.2 for 2.7 mM
      carbonmonoxyhemoglobin (COHb); 1.6 for 2.0 mM ATP; and 1.2 for a 50/50% (v/v)
      glycerol-water mixture. Intracellular viscosity and the electric field gradients
      experienced by Li+ when traversing the spectrin-actin network therefore are not
      responsible for the large values of the T1/T2 ratios observed in Li(+)-loaded
      RBCs. We conclude that the RBC membrane is the major Li+ binding site in Li(+)
      loaded RBCs (Kb = 215 +/- 36 M-1) and that the binding of Li+ to COHb, BPG,
      spectrin-actin, or ATP is weak. Partially relaxed 7Li NMR spectra of Li(+)
      containing RBC membrane suspensions indicated the presence of two relaxation
      components, one broad and one narrow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257685
TI  - Mass spectrometric characterization of arachidonate-containing plasmalogens in
      human pancreatic islets and in rat islet beta-cells and subcellular membranes.
AB  - Pancreatic islets, when stimulated with D-glucose, secrete insulin by processes
      requiring glycolytic metabolism and generation of ATP. Hydrolysis of membrane
      phospholipids also occurs in glucose-stimulated islets, resulting in accumulation
      of nonesterified arachidonate, which facilitates Ca2+ entry and the rise in beta
      cell [Ca2+] that triggers insulin secretion. Glucose-induced hydrolysis of
      arachidonate from islet phospholipids is mediated in part by an ATP-stimulated,
      Ca(2+)-independent (ASCI) phospholipase A2 (PLA2) which prefers plasmenyl over
      diacyl phospholipid substrates. Here we characterize the endogenous plasmalogen
      content of islet cells and subcellular membranes. Fast atom bombardment mass
      spectrometric analyses demonstrated that three of the most abundant molecular
      species of ethanolamine phospholipids in rat pancreatic islets were plasmalogens
      with sn-2 arachidonate residues and palmitic, oleic, or stearic aldehyde
      residues, respectively, in the sn-1 position. Purified populations of beta-cells
      prepared by fluorescence-activated cell sorting were also found to contain these
      plasmenylethanolamine molecular species in abundance similar to that in intact
      islets and greater than that in islet alpha-cells. Both islet plasma membranes
      (PM) and endoplasmic reticulum (ER) also contained these plasmenylethanolamine
      species, which accounted for 42% (PM) to 64% (ER) of the ethanolamine
      phospholipid arachidonate content of these membranes, as measured by stable
      isotope dilution mass spectrometry. Plasmenylethanolamine species were also
      abundant constituents of human pancreatic islets (accounting for 58% of their
      ethanolamine phospholipid arachidonate content) and were hydrolyzed more rapidly
      than diacyl ethanolamine phospholipid by human islet cytosolic ASCI-PLA2. Both
      secretagogue-induced eicosanoid release and insulin secretion from human islets
      were attenuated by an ASCI-PLA2 suicide substrate which sterically resembles
      plasmalogens. These observations are consistent with the hypotheses that islet
      beta-cell ASCI-PLA2-catalyzed hydrolysis of arachidonate from endogenous
      plasmenylethanolamine substrates may occur in membrane compartments which
      participate in regulation of the beta-cell cytosolic [Ca2+] and that this may be
      an intermediary biochemical event in the induction of insulin secretion.

PMID- 8257686
TI  - Heat shock protein 70 is associated in substoichiometric amounts with the rat
      hepatic glucocorticoid receptor.
AB  - The 70-kDa heat shock protein (hsp70) has been shown to be an important
      participant in several intracellular events, including protein folding and
      trafficking. Hsp70 binds to many, if not all, proteins during their translation
      and maintains its association with some protein complexes as a subunit. We have
      examined the possibility that hsp70 may be associated with one or more forms of
      the rat hepatic glucocorticoid receptor (GR). Unliganded GR was
      immunoprecipitated from cytosol with the anti-GR monoclonal antibody BUGR2 and
      then subjected to western blotting. Both hsp70 and the 90-kDa heat shock protein
      (hsp90) were found to be specifically associated with the GR. Hsp70 was also
      bound to the liganded unactivated and activated (transformed) forms of the GR
      complex, while as expected, hsp90 was absent from the activated GR.
      Immunoprecipitation of cytosolic hsp70 with the anti-hsp70 monoclonal antibody
      N27 resulted in coprecipitation of GR. The components of the immunopurified GR
      were also analyzed by laser densitometry after polyacrylamide gel electrophoresis
      and Coomassie blue staining. These experiments revealed that hsp70 is bound to
      the GR in an approximate 1:5 ratio. Unactivated GR complexes isolated via a
      ligand affinity purification scheme contained hsp90 and trace amounts of hsp70.
      Collectively, these experiments demonstrate that hsp70 is specifically associated
      with several forms of the native rat hepatic GR, although its binding is
      substoichiometric. This is in direct contrast to hsp90, which binds as a dimeric
      subunit to the heteromeric unactivated GR complex.

PMID- 8257687
TI  - Site-directed mutagenesis of the Na,K-ATPase: consequences of substitutions of
      negatively-charged amino acids localized in the transmembrane domains.
AB  - Site-directed mutagenesis was used to examine the importance of five carboxyl
      containing amino acids localized in the putative membrane-spanning regions of the
      Na,K-ATPase (i.e., E327, E778, D803, D807, and D925 of the rat alpha 2 isoform).
      The substitutions were introduced into a cDNA encoding a ouabain-resistant
      isoform (i.e., rat alpha 2* which was mutated to encode a ouabain-resistant
      isoform), and the effect of these substitutions on Na,K-ATPase function was
      assessed by screening the altered enzymes for their ability to confer ouabain
      resistance when expressed in otherwise ouabain-sensitive cells. The expression of
      the alpha isoform containing certain substitutions at positions 327 and 925 was
      able to confer ouabain resistance to HeLa cells while the expression of rat alpha
      2* containing substitutions at positions 778, 803, and 807 was not. In
      particular, amino acids in each of these positions were substituted with leucine
      to evaluate the importance of the carboxyl-containing side chain. The ability of
      rat alpha 2* containing E327L and D925L to confer ouabain resistance to HeLa
      cells indicates that neither the negative charge nor the oxygen-containing side
      chain is absolutely essential for overall function in this position. In contrast,
      the inability of rat alpha 2* carrying E778L, D803L, and D807L to confer ouabain
      resistance suggests that the naturally occurring amino acid may be more critical
      structurally and/or functionally for the Na,K-ATPase. Other more conservative
      substitutions introduced to further characterize the role of particular amino
      acid side chains include E327D, E327Q, D803N, D803E, and D925N.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257688
TI  - Characterization of human placental insulin-like growth factor-I/insulin hybrid
      receptors by protein microsequencing and purification.
AB  - Protein microsequencing of human placental IGF-I receptors purified by
      immunoaffinity chromatography using IGF-I receptor specific monoclonal antibody
      revealed amino acid sequences of both IGF-I and insulin receptors. Since this
      finding indicated the presence of IGF-I/insulin receptor hybrids, hybrid
      receptors were further purified by immunoaffinity chromatography using insulin
      receptor specific monoclonal antibody. The molecular size of the nonreduced
      hybrid receptor was approximately 350K, indicating that the IGF-I and insulin
      receptor alpha beta halves were disulfide-linked. The ratio of IGF/insulin
      binding activity of purified hybrid receptors was approximately 25 when measured
      using tracer amounts of radioactive ligands. 125I-IGF binding to these receptors
      was inhibited by IGF-I and insulin with IC50s of approximately 2 and
      approximately 1000 nM, respectively. 125I-Insulin binding to these receptors was
      similarly inhibited by IGF-I and insulin with IC50 of approximately 3 nM.
      Autophosphorylation and kinase activities of the hybrid receptor were stimulated
      by IGF-I more effectively than insulin in a dose-dependent manner. Thus, the
      present studies indicate that hybrid receptors purified from human placenta have
      the functional properties of an IGF-I receptor.

PMID- 8257689
TI  - Direct identification of an extracellular agonist binding site in the renal V2
      vasopressin receptor.
AB  - To purify the renal V2 receptor and identify domains involved in hormone binding,
      photoaffinity labeling of the membrane-bound bovine V2 receptor with a tritium
      labeled photoreactive vasopressin agonist was performed. The labeled 30,000 M(r)
      protein was purified to homogeneity by anion-exchange chromatography, isoelectric
      focusing, gel filtration, gel electrophoresis, and reversed-phase HPLC. N
      terminal sequencing showed that the isolated protein which contains the
      covalently bound hormonal ligand, represents an N-terminal truncated bovine V2
      receptor. The purified labeled V2 vasopressin receptor protein was digested with
      V8 protease, and peptide fragments were isolated. Protein microsequencing and
      comparison with the cDNA sequence of a cloned PCR product identified two extra-
      and two intracellular peptides of the bovine V2 receptor. Radioactivity was
      incorporated into two amino acid residues localized in the second extracellular
      domain. Our results indicate that this extracellular domain is involved in
      peptide agonist binding of the V2 receptor.

PMID- 8257690
TI  - Deletion of exon 21 of the insulin receptor eliminates tyrosine kinase activity
      but preserves mitogenic signaling.
AB  - To study the function of exon 21 of the insulin receptor, a mutant human insulin
      receptor lacking this domain was constructed. The mutant HIR delta E21 cDNA was
      transfected into Rat-1 fibroblasts and stable cell lines were selected. The HIR
      delta E21 receptors were expressed on the cell surface, and they bound insulin
      with the same affinity as did the wild-type-expressing cell line, hIRcB. The HIR
      delta E21 receptors did not display detectable autophosphorylation or kinase
      activity, and as expected, internalization was impaired and metabolic signaling
      properties were absent. Unexpectedly, insulin's ability to stimulate DNA
      synthesis in cells expressing HIR delta E21 receptors was far greater than that
      in the parental Rat-1 cells and equal to that measured in the hIRcB cell line.
      The enhanced mitogenic signaling properties of the HIR delta E21 receptors was
      confirmed by showing that treatment of HIR delta E21 cells with a human-specific
      insulin-mimetic anti-insulin receptor antibody also led to enhanced DNA
      synthesis. Thus, although no insulin receptor autophosphorylation or kinase
      activity was detectable in HIR delta E21 cells, these cells displayed enhanced
      insulin-induced mitogenic signaling. These results suggest that an alternative
      non-kinase-dependent stimulus-response pathway exists for the long-term
      biological effects of insulin.

PMID- 8257691
TI  - Molecular mechanism of colchicine action: induced local unfolding of beta
      tubulin.
AB  - Colchicine, the classic antimitotic poison, disrupts cell division by preventing
      proper assembly of microtubules in the mitotic spindle. Colchicine is known to
      act by binding to tubulin, the heterodimeric subunit of microtubules. How this
      binding to tubulin changes the structure of the protein and results in
      polymerization poisoning has not been characterized. The structural locus of
      spectroscopically detected conformational changes induced by colchicine is
      unknown. We report here that colchicine induces the unfolding of a small region
      in the carboxyl-terminal region of beta-tubulin, around Arg-390. This unfolding
      is detected by proteolysis with trypsin and chymotrypsin. Chymotrypsin cleaves
      this region after Phe-389, and trypsin cleaves after Lys-392. The unfolded region
      appears to be the carboxyl end of an amphipathic helix in the absence of
      colchicine, and we propose that this unfolding prevents contacts necessary for
      assembly. Our results suggest that beta-tubulin is exposed on the growing end of
      the microtubule, which provides a mechanism for coupling GTP hydrolysis to
      polymerization.

PMID- 8257692
TI  - Collapse of parallel folding channels in dihydrofolate reductase from Escherichia
      coli by site-directed mutagenesis.
AB  - The rate-limiting steps in the folding of dihydrofolate reductase from
      Escherichia coli have been shown to involve the conversion of a set of four
      intermediates to a corresponding set of native conformers via four parallel
      channels [Jennings et al. (1993) Biochemistry 32, 3783-3789]. Fluorescence and
      absorbance studies of the unfolding and refolding of the C85S/C152E double mutant
      at various final urea concentrations reveal two slow folding reactions, two fewer
      than observed in the wild-type protein. Refolding in the presence of
      substoichiometric levels of the inhibitor methotrexate shows that the two
      remaining slow reactions correspond to two parallel channels which lead to a pair
      of native conformers capable of binding the inhibitor. A combination of stopped
      flow circular dichroism and cofactor binding studies confirms that the four
      parallel channels observed in the wild-type protein have collapsed into two
      channels in the mutant. Kinetic and equilibrium studies of the single cysteine
      mutants suggest that replacements of Cysteine-85 which perturb the hydrophobic
      core containing this side chain are responsible for the simplification of the
      kinetic mechanism. These results demonstrate that at least two of the parallel
      folding channels in dihydrofolate reductase arise when tertiary structure
      develops and are not dependent upon cis/trans isomerization at prolyl peptide
      bonds.

PMID- 8257693
TI  - Solution dynamics of p21ras proteins bound with fluorescent nucleotides: a time
      resolved fluorescence study.
AB  - The solution dynamics of normal and transforming p21ras proteins in both the GTP-
      and GDP-bound forms were examined with time-resolved fluorescence spectroscopy.
      The fluorescent 2'(3')-O-(N-methylanthraniloyl) derivatives (mant derivatives) of
      GTP, dGTP, and GDP and the aminocoumarin and fluorescein derivatives of GTP and
      GDP were synthesized and used as reporter groups. The fluorescence lifetimes at 5
      degrees C of the mant nucleotide derivatives increased from approximately 4 ns in
      solution to approximately 9 ns when bound to p21ras. At 30 degrees C, there was a
      7.8% difference in lifetime between normal p21ras.mantGTP and p21ras.mantGDP, but
      no difference between similar complexes of the [Asp-12]p21ras protein. These data
      are consistent with steady-state fluorescence intensity differences among
      p21ras.mantGTP, p21ras.mantGDP, and the free nucleotides. Rotational correlation
      times for the mantGTP- and mantGDP-bound p21 proteins, N-ras, K-ras, and H-ras,
      were similar at 26 ns (5 degrees C), which is significantly longer than the 15-ns
      rotational correlation time predicted for a globular 21,000-Da protein. The p21
      bound fluorescein and aminocoumarin nucleotide derivatives reported correlation
      times of 19 and 29 ns, respectively. Global analysis of the three fluorophore.p21
      complexes with linked protein rotational correlation functions were best fit with
      a common rotational correlation time of 28 ns. Gel permeation chromatography of
      the GDP and mantGDP complexes of normal p21N-ras also showed greater apparent
      molecular weights than were expected in both cases, demonstrating that the high
      rotational correlation times obtained from time-resolved fluorescence
      measurements were not a result of the introduction of the fluorophore.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257694
TI  - Rationally designing the accumulation of a folding intermediate of barnase by
      protein engineering.
AB  - A method for the stabilization of transient folding intermediates is presented.
      Barnase folds and unfolds via such an intermediate. Mutations that destabilize
      the folded state relative to the folding intermediate had been previously
      identified from the free energy profiles for the unfolding of mutant proteins. It
      is predicted that the accumulation of such mutations should lead to the
      intermediate being the most stable species at certain concentrations of
      denaturant. Mutants were prepared that contained combinations of such mutations.
      The behavior of these mutants on urea denaturation was studied by probes for
      tertiary structure (fluorescence, near-UV CD), secondary structure (far-UV CD),
      and hydrodynamic volume (size-exclusion chromatography). Whereas wild-type shows
      a two-state transition in all cases, with the same thermodynamic values being
      found by all probes, some of the mutants show different transitions with
      different structural probes. On increasing concentration of denaturant, the
      tertiary structure of these mutants is lost before all the secondary structure
      and before the protein shows the maximum expanded volume that is characteristic
      of the unfolded state. These mutants thus accumulate an intermediate state at
      equilibrium under certain urea concentrations. The intermediate state retains
      some degree of secondary structure but has a disrupted tertiary structure, and
      its degree of compactness is intermediate between the folded and the unfolded
      forms, probably expanding with increasing concentration of denaturant. The
      accumulation of the intermediate should allow its direct characterization by
      spectroscopy, especially NMR.

PMID- 8257695
TI  - Parental nucleosomes segregated to newly replicated chromatin are underacetylated
      relative to those assembled de novo.
AB  - Antibodies specific for acetylated histone H4 were used to examine the
      acetylation state of parental histones that segregate to newly replicated DNA. To
      generate newly replicated chromatin containing only segregated parental
      nucleosomes, isolated nuclei were labeled with [3H]TTP in vitro; alternatively,
      whole cells were labeled with [3H]thymidine in the presence of cycloheximide.
      Soluble chromatin was prepared by micrococcal nuclease digestion, and subjected
      to immunoprecipitation with "penta" antibodies (Lin et al., 1989). In sharp
      contrast to nucleosomes containing newly synthesized, diacetylated H4 (Perry et
      al., 1993), chromatin replicated in vitro was only marginally susceptible to
      immunoprecipitation. Control experiments established that bona fide acetylated
      chromatin was selectively immunoprecipitated by the same techniques and that
      segregated nucleosomes were not disassembled during treatment with "penta"
      antibodies. When replication was coupled to an in vitro histone acetylation
      system, the enrichment for segregated nucleosomes in the immunopellet increased
      approximately 3-fold, demonstrating that changes in the acetylation state of
      segregated histones can be detected immunologically and that parental histones on
      new DNA are accessible to acetyltransferases during, or immediately after, DNA
      replication. In vivo pulse-chase experiments, performed in the presence of
      cycloheximide, confirmed these results. Uptake experiments further established
      that concurrent histone acetylation did not alter the rate of DNA synthesis in
      vitro. Our results provide evidence that replication-competent chromatin is not
      obligatorily acetylated, and indicate that the acetylation status of segregated
      histones may be maintained during chromatin replication. The possible
      significance of this, with respect to the regulation of chromatin higher order
      structures during DNA replication, and the propagation of transcriptionally
      active vs inactive chromatin structures, is discussed.

PMID- 8257696
TI  - Eicosanoid metabolism in cholesterol-enriched arterial smooth muscle cells.
      Evidence for reduced posttranscriptional processing of cyclooxygenase I and
      reduced cyclooxygenase II gene expression.
AB  - Eicosanoid biosynthetic activity by the cyclooxygenase pathway is reduced in
      smooth muscle cell-derived foam cells [Pomerantz, K.B., & Hajjar, D.P. (1989) J.
      Lipid Res. 30, 1219-1231; Pomerantz, K.B., & Hajjar, D.P. (1990) Biochemistry 29,
      1892-1899]. The present study identifies those mechanisms which contribute to
      reduced production of cyclooxygenase products following cholesterol enrichment of
      arterial smooth muscle cells. Cyclooxygenase activity, as assessed by the
      conversion of exogenous arachidonate to 6-keto-PGF1 alpha, was reduced
      approximately 8-fold in intact lipid-laden cells relative to untreated cells.
      Microsomes from cholesterol-enriched cells also converted less [3H]arachidonic
      acid to 6-keto-PGF1 alpha and PGE2 relative to microsomes from untreated cells.
      The reduction in cyclooxygenase activity paralleled the reduced mass of the
      constitutive form of cyclooxygenase (COX-1) and PGI2 synthase by approximately
      80% and 33%, respectively. Northern blot hybridization analyses of COX-1 mRNA
      steady-state levels revealed no differences between normal and cholesterol
      enriched cells under basal conditions, indicating that cholesterol enrichment did
      not alter COX-1 gene expression. Furthermore, cholesterol enrichment did not
      alter the relative levels of COX-1 mRNA expression over time following exposure
      of the cells to actinomycin D, indicating that cholesterol enrichment did not
      significantly alter the rate of COX-1 mRNA degradation. Recovery of PGI2
      biosynthesis in untreated cells exposed to serum following the inactivation of
      COX occurred within 12 h, while the recovery of COX activity in lipid-enriched
      cells did not return to levels observed in untreated cells even after up to 48 h,
      suggesting that the induction of COX-2 (inducible form of cyclooxygenase)
      synthesis by growth factors or cytokines is impaired. Indeed, cholesterol
      enrichment attenuated IL-1 beta-, PDGF-, and TNF alpha-induced PGI2 synthesis
      relative to controls and was consistent with the results of in vitro labeling
      experiments demonstrating that cholesterol enrichment reduced the incorporation
      of [35S]methionine into immunoprecipitable COX-1 and COX-2 following induction by
      PDGF. Cholesterol enrichment also reduced the induction of COX-2 mRNA steady
      state levels following exposure to PDGF. Taken together, these data demonstrate
      that reduced eicosanoid synthesis in smooth muscle-derived foam cells is due, in
      part, to impaired transcription of mRNA for COX-1 and COX-2 as well as fatty acid
      remodeling in membrane phospholipids. These findings support the hypothesis that
      cholesterol enrichment alters posttranscriptional processing of COX-1 expression,
      as well as altering COX-2 gene expression.

PMID- 8257697
TI  - Involvement of threonine 234 in catalysis of tyrosyl adenylate formation by
      tyrosyl-tRNA synthetase.
AB  - There is a mobile loop in the tyrosyl-tRNA synthetase that contains the KMSKS
      signature sequence of class I aminoacyl-tRNA synthetases. As it has not been
      possible to determine the role of the mobile loop in catalysis from X-ray
      crystallographic studies, we are investigating its importance by a series of site
      directed mutagenic and kinetic studies. Here we examine the role of threonine 234
      (T234) in the catalysis of tyrosyl adenylate formation by tyrosyl-tRNA synthetase
      from Bacillus stearothermophilus. This residue is the carboxy-terminal residue in
      the signature sequence and is either a serine or threonine in eight of the ten
      class I aminoacyl-tRNA synthetases isolated from Escherichia coli. Kinetic
      analyses of tyrosyl adenylate formation in the mutant enzymes indicate that k3,
      the forward rate constant for the formation of tyrosyl adenylate, is reduced 500
      fold on mutation of T234 to alanine. In contrast, mutation of T234 to serine
      results in only a 4-fold decrease in k3, suggesting that the loss of the hydroxyl
      group in the T234A mutant is responsible for its decreased reaction rate.
      Deletion of the hydroxyl group destabilizes the transition state for the
      formation of tyrosyl adenylate by 2.7 kcal/mol. The transition state is also
      destabilized by 1.4 kcal/mol on the mutation of K230 to alanine. The effects of
      mutation of both T234 and K230 to alanine are less than additive; there is a
      coupling energy of -1.3 kcal/mol in the transition state. The effects of mutating
      K230 and T234 to alanine are also nonadditive in the E.Tyr-AMP complex (coupling
      energy = -1.9 kcal/mol).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257698
TI  - Mutation of lysine 233 to alanine introduces positive cooperativity into tyrosyl
      tRNA synthetase.
AB  - Tyrosyl-tRNA synthetase from Bacillus stearothermophilus is a dimeric enzyme
      which displays half-of-sites reactivity with respect to the binding of both
      tyrosine and ATP. The binding of both substrates follows Michaelis-Menten
      kinetics. Mutation of lysine 233 to alanine (K233A) decreases the affinity of the
      active subunit for ATP at both saturating and subsaturating tyrosine
      concentrations (from the Hill plot, kcat = 0.56 s-1, nH = 1.54, Kd = 372 mM at 50
      microM tyrosine). In addition, this mutant displays sigmoidal kinetics
      (characteristic of positive cooperativity) with respect to the binding of ATP.
      These two effects can be reversed by the addition of NaCl (0.5 m final
      concentration) or by a second alanine mutation at either position K230 or T234.
      The effect of either NaCl or second site mutation is to increase the binding
      affinity of the K233A mutant for ATP (KATP values are 22 mM for the K233A mutant
      in the presence of 0.5 M NaCl, 0.16 mM for the K230A/K233A mutant, and 0.14 mM
      for the K233A/T234A mutant). With the restoration of the tight binding of ATP,
      Michaelis-Menten kinetics are restored since the kinetic analysis of tyrosyl
      adenylate formation involves only binding of ATP to the active subunit. It is
      likely that the physical mechanism for the positive cooperativity present in the
      K233A mutant actually exists in the wild-type enzyme but is not observed
      kinetically due to the initial binding of ATP to the active subunit. These
      results indicate that, in some cases, a decrease in substrate affinity is
      sufficient to introduce cooperativity into a noncooperative enzyme.

PMID- 8257699
TI  - Mutational and kinetic analysis of a mobile loop in tyrosyl-tRNA synthetase.
AB  - The role of a mobile loop in tyrosyl-tRNA synthetase has been investigated by
      mutating each amino acid in the loop and kinetically analyzing the effect that
      each mutation has on the formation of the enzyme-bound tyrosyl adenylate
      intermediate. Kinetic analyses of mutations at three of the nine positions in the
      loop, K230, K233, and T234, have been reported elsewhere (Fersht et al., 1988;
      First & Fersht, 1993a,b). In this paper, the kinetic analyses of mutants in the
      remaining six positions, as well as a mutant in which the entire loop is deleted,
      are reported. With the exception of E235, which stabilizes the E.-[Tyr-ATP]++ and
      E.Tyr.ATP complexes by 1.0 and 1.2 kcal/mol, respectively, none of the remaining
      amino acids appears to be directly involved in the catalytic mechanism of the
      enzyme. Instead, mutation of these residues results in small alterations in the
      stability of E.Tyr.ATP, E.[Tyr-ATP]++ and E.Tyr.AMP.PPi complexes. The precise
      amino acid residues which stabilize each state vary, suggesting that the loop
      adopts different conformations in each of the complexes with the most highly
      constrained conformation being in the E.[Tyr-ATP]++ complex. Deletion of the loop
      reveals that the net effect of the loop in catalysis is two-fold: (1) to
      destabilize the E.Tyr.ATP complex preceding formation of the E.[Tyr.ATP]++
      complex and (2) to stabilize the E.[Tyr-ATP]++ complex, indicating that the
      involvement of the loop in catalysis occurs at the expense of ATP-binding
      energy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257700
TI  - O6-methylguanine in DNA inhibits replication in vitro by human cell extracts.
AB  - To study the effects of methylation damage on DNA replication in vitro, the
      plasmid pSVori containing the SV40 origin of replication was reacted with N
      methyl-N-nitrosourea and used as a substrate for SV40 T antigen dependent
      replication by HeLa cell extracts. The plasmid was methylated with a range of N
      methyl-N-nitrosourea concentrations that introduced an average of 0.3-2.5 O6
      methylguanine and equal amounts of 3-methyladenine lesions per DNA molecule. When
      methylated plasmid was incubated with extract of Mex-HeLaMR cells under
      conditions favoring DNA replication, an impairment of replication was observed as
      the accumulation of incompletely replicated form II plasmid molecules. These
      extracts simultaneously performed a T antigen independent, DpnI-sensitive DNA
      repair synthesis that increased with increasing DNA damage. Subtraction of this
      repair DNA synthesis revealed that methylation inhibited overall replication. At
      low levels of methylation (< or = 1 O6-methylguanine and < or = 1 3-methyladenine
      lesion per plasmid), inhibition was transient, while more extensive damage
      resulted in apparently irreversible inhibition of replication. Removal of O6
      methylguanine by pretreatment of the methylated plasmid with purified human O6
      methylguanine-DNA methyltransferase restored replication to almost normal levels.
      When the methylated plasmid was replicated by extracts of Mex+ HeLaS3 cells
      proficient in the repair of O6-methylguanine, a lower level of inhibition and
      less repair DNA synthesis was observed. The inhibition of DNA synthesis and the
      stimulation of repair DNA synthesis are thus both largely due to the presence of
      O6-methylguanine in DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257701
TI  - Herpes simplex virus type 1 ribonucleotide reductase large subunit: regions of
      the protein essential for subunit interaction and dimerization.
AB  - We have constructed a series of random N-terminal deletions of the large subunit
      (R1) of the herpes simplex virus type 1 ribonucleotide reductase. Deletions
      extended throughout the R1 gene open reading frame and, in total, 31 different
      truncated polypeptides were expressed in Escherichia coli using the T7 expression
      system. N-Terminal truncations were analyzed for their interaction with the small
      subunit (R2) of ribonucleotide reductase using a sensitive enzyme-linked
      immunosorbent assay (ELISA) method and for their ability to complement R2 in
      ribonucleotide reductase assays. Truncated proteins were also tested for
      homodimerization using gel-filtration chromatography. The results identified a
      region of R1 between amino acids 349 and 373 which was essential for subunit
      interaction. Proteins lacking up to 348 amino-terminal residues associated with
      R2 and complemented R2 in ribonucleotide reductase assays. Proteins commencing at
      amino acid 373 and beyond did not interact with R2 and were inactive in enzyme
      assays. Using a plasmid which expressed an N-terminal deleted protein commencing
      at amino acid 247, we constructed two defined C-terminal deletions to give
      proteins comprising amino acids 247-434 and 247-996 of R1. Neither of these
      truncated proteins bound R2 and we concluded that a second region between amino
      acids 996 and 1137 (the C-terminus) is required for interaction with R2. Gel
      filtration studies indicated that deletion of the first 420 amino acids from R1
      did not affect dimerization. However, deletions of 457 amino acids and larger
      gave proteins which existed as monomers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257702
TI  - Comparison of the lysine binding functions of lipoprotein(a) and plasminogen.
AB  - Regions of apoprotein(a) of lipoprotein(a) [Lp(a)] exhibit striking primary
      sequence homology to the kringles of plasminogen. The kringles of plasminogen are
      lysine binding structures and mediate interactions of plasmin(ogen) with
      substrates and inhibitors. In the current study, the lysine binding properties of
      Lp(a) have been compared to those of plasminogen and isolated kringle 4 of
      plasminogen (K4). An analytical assay was implemented to quantitate the
      interaction of kringle-containing molecules with lysine-Sepharose beads.
      Radioiodinated ligands, Lp(a), plasminogen, and K4, bound to the beads, and their
      interactions were inhibited by lysine analogues in a dose-dependent fashion. A
      series of omega-aminocarboxylic acids inhibited Lp(a), plasminogen, and K4
      binding to the lysine-Sepharose beads, but marked differences in the
      effectiveness of these compounds were observed with each ligand. In this series
      of compounds, 6-aminohexanoic acid was the most potent inhibitor of binding to
      lysine-Sepharose for all three ligands. The pH had little effect on the
      inhibition of plasminogen binding by these compounds. For Lp(a), a low pH caused
      a marked decrease in inhibition by the 5-carbon and 4-carbon omega-amino acids.
      In addition, tranexamic acid was 750-fold more potent than lysine in inhibiting
      plasminogen and 55-fold more potent for K4 binding to the beads. In contrast, the
      differential potency of these compounds on Lp(a) binding was only 3-fold. These
      results suggest that the kringles of Lp(a) possess lysine binding functions which
      are similar, but not identical, to those of plasminogen and its K4.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257703
TI  - Site-directed mutagenesis in hemoglobin: functional and structural study of the
      intersubunit hydrogen bond of threonine-38(C3)alpha at the alpha 1-beta 2
      interface in human hemoglobin.
AB  - To clarify the functional and structural roles of Thr-38 alpha at the alpha 1
      beta 2 interface, two artificial alpha-chain mutants, in which Thr-38 alpha is
      replaced by Ser (Hb T38 alpha S) or Val (Hb T38 alpha V), were prepared. Thr-38
      alpha is one of the highly conserved amino acid residues in hemoglobins and forms
      a hydrogen bond to Asp-99 beta, which is a crucial residue to stabilize the T
      state, via a water molecule in the deoxygenated form. We investigated their
      oxygen binding properties together with structural consequences of the mutations
      by using various spectroscopic probes. Their oxygen equilibrium curves showed
      small changes in the oxygen binding properties. Structural probes such as
      ultraviolet-region derivative and oxy-minus-deoxy difference spectra, resonance
      Raman scattering, and 1H-NMR spectra also indicated that the oxy and deoxy forms
      of these mutants show spectra characteristic of the R and T states, respectively,
      and the R-T transition is not very disturbed. The present structural and
      functional data of the mutants imply that the hydrogen bond between Thr-38 alpha
      and Asp-99 beta does not play a key role in stabilizing the deoxy T structure,
      which is in sharp contrast to the role of the hydrogen bond between Tyr-42 alpha
      and Asp-99 beta, and suggest that the interactions via the intersubunit hydrogen
      bonds are highly site-specific, depending on the amino acid residue which
      participates in them.

PMID- 8257704
TI  - An active-site peptide containing the second essential carboxyl group of
      dextransucrase from Leuconostoc mesenteroides by chemical modifications.
AB  - The treatment of Leuconostoc mesenteroides B-512F dextransucrase with 10 mM 1
      ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC) and glycine ethyl ester (GEE)
      inactivated the enzyme almost completely within 24 min where the modification of
      one carboxyl group/mol of the enzyme by EDC was attained. Though 30 mM diethyl
      pyrocarbonate (DEP) also inactivated the enzyme, about 35% of the activity
      remained during a 36-min incubation. When 10 mol of imidazole residues/mol of the
      enzyme was modified by DEP, 50% of the activity was still retained. The addition
      of the substrate sucrose greatly retarded the enzyme inactivation by EDC.
      However, the addition of dextran slightly protected the inactivation of the
      glucosyl-transferring activity and accelerated the inactivation of the sucrose
      cleaving activity. In the case of DEP, the addition of sucrose or dextran gave no
      influence on the inactivation of the enzyme. Therefore, the carboxyl group seemed
      to play a more important role in the substrate binding and in the catalytic
      activity of the dextransucrase than the imidazolium group. Differential labeling
      of Leuconostoc dextransucrase by EDC was conducted in the presence of a sucrose
      analog, sucrose monocaprate. The fluorescent probe N-(1-naphthyl)ethylenediamine
      (EDAN) was used as the nucleophile instead of GEE. A fluorescent labeled peptide
      was isolated from a trypsin digest of the EDC-EDAN modified enzyme. The amino
      acid sequence of the isolated peptide was Leu-Gln-Glu-Asp-Asn-Ser-Asn-Val-Val-Val
      Glu-Ala.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257705
TI  - Analysis of the redox reaction of an archaebacterial copper protein, halocyanin,
      by electrochemistry and FTIR difference spectroscopy.
AB  - Halocyanin is a recently discovered archaebacterial copper protein classified as
      "type I" small blue copper protein (Scharf, B., Ph.D. Thesis, University of
      Bochum, Germany). Its redox properties were investigated by a combination of
      protein electrochemical and spectroscopic techniques. Using electrochemical
      reactions in an ultrathin-layer electrochemical cell developed for UV/vis and IR
      spectroscopy, halocyanin could be quantitatively and reversibly oxidized and
      reduced. The titration of the absorption band at 600 nm can be perfectly
      described by a Nernst curve with n = 1 electron transferred; a quantitative fit
      yields a midpoint potential, Em, of 183 mV (vs SHE) at a pH of 7.3. The midpoint
      potential falls constantly from +333 mV at pH 4 to +119 mV at pH 10, with three
      regions around pH 4.5, 6.5, and 8.5 where the pH dependence is ca. -60 mV/pH
      unit, indicating the uptake of a proton with the reduction. By analogy with other
      small type I copper proteins, the three pK values suggested by the pH dependency
      of Em might be associated with three histidines which interact with the redox
      site. Electrochemically induced reduced-minus-oxidized Fourier transform infrared
      difference spectra in the 1800-1000 cm-1 range at neutral pH show a number of
      strong difference bands between ca. 1700 and 1600 cm-1 as well as smaller
      difference structures between 1600 and 1200 cm-1. The maximum amplitude of the
      difference bands--only ca. 1% of the amide-I absorption at ca. 1639 cm-1-
      indicates that only small protein rearrangements occur upon the redox
      transition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257706
TI  - ENDOR and ESEEM studies of cytochrome c oxidase: evidence for exchangeable
      protons at the CuA site.
AB  - Electron nuclear double resonance (ENDOR) and electron spin echo envelope
      modulation (ESEEM) spectroscopies were used to study whether protons in the
      immediate protein environment around CuA in cytochrome c oxidase are susceptible
      to solvent exchange. The enzyme was incubated in buffered D2O under resting or
      turnover conditions for 90 min and then frozen to quench the hydrogen/deuterium
      exchange process. ENDOR spectra of the deuterated sample were essentially
      identical to those of control samples. The ESEEM spectra, however, provided a
      clear indication of the introduction of deuterium into the CuA environment
      following incubation in buffered D2O. The extent of deuterium incorporation was
      not affected by enzyme turnover. An analysis of the ESEEM data indicated that
      water is in reasonably close proximity to the CuA site, but not in the immediate
      coordination sphere of the metal(s). We estimate a minimum distance of 5.4 A
      between the CuA center and the protein/water interface. This relatively short
      surface separation distance is consistent with the role of CuA as the immediate
      oxidant of cytochrome c in the cytochrome oxidase (Hill, B. C. (1991) J. Biol.
      Chem. 266, 2219-2226).

PMID- 8257707
TI  - Nitrogenase reactivity: effects of pH on substrate reduction and CO inhibition.
AB  - Molybdenum nitrogenase is composed of two separately purified proteins designated
      the iron protein (Fe protein) and the molybdenum-iron protein (MoFe protein),
      with the latter containing the substrate reduction site which is a metal cluster
      designated the iron-molybdenum cofactor (FeMo cofactor). In addition to its
      physiological substrates H+ and N2, nitrogenase reduces a number of
      nonphysiological substrates (e.g. C2H2 and N3-) and interacts with a number of
      similar molecules (e.g. CH3NC and CO) that serve as specific inhibitors. Despite
      their great diversity, all substrates are reduced by multiples of two electrons
      and require equivalent numbers of electrons and protons. Although the electron
      donor to a substrate is believed to be FeMo cofactor, the nature of the proton
      donor is unknown and might be different for different substrates. Here we report
      a three-component buffer assay system that eliminates variables of buffer type,
      ionic strength, and ATP and reductant availability and that is compatible with
      the nitrogenase system in the pH range 5.0-9.8. Preincubated studies and studies
      of the effects of pH on H2 evolution under Ar, H2 evolution under N2, H2
      evolution under CO, and C2H2 reduction show that there is a group with a pK of
      ca. 6.3 that must be deprotonated for substrate reduction to occur and that there
      is a group with a pK of ca. 9.0 that must be protonated for substrate reduction
      to occur.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257708
TI  - Cytochrome P450BM-3 (CYP102): regiospecificity of oxidation of omega-unsaturated
      fatty acids and mechanism-based inactivation.
AB  - Cytochrome P450BM-3 preferentially oxidized fatty acids with terminal double or
      triple bonds to the omega-2 hydroxylated fatty acids rather than, respectively,
      to the epoxide or diacid metabolites. The enzyme is inactivated during catalytic
      turnover of long, terminally unsaturated fatty acids but not by the analogous
      medium-length fatty acids. Enzyme inactivation by 17-octadecynoic acid and 16
      hydroxy-17-octadecynoic acid is due to alkylation of the prosthetic heme group to
      given an adduct tentatively identified as N-(2-oxo-3-hydroxy-17
      carboxyheptadecyl)protoporphyrin IX by its chromatographic and spectroscopic
      properties. Catalytic turnover of 17-octadecenoic acid also results in heme
      modification. Fatty diacid monoethyl thioesters are introduced as a new class of
      irreversible inhibitors that exploit the omega-2 oxidation specificity of
      cytochrome P450BM-3. Catalytic oxidation of the monoethyl thioesters of
      dodecanedioic and hexadecanedioic acids results in enzyme inactivation and
      formation of the parent diacids as metabolites. Limited tryptic digestion of the
      enzyme after incubation with the monoethyl thioester of [14C]hexadecanedioic acid
      shows that the inactivating agent binds covalently to both the heme and flavin
      domains. This finding, and the observation that glutathione prevents inactivation
      of the enzyme by the monoethyl thioesters, indicate that a diffusible metabolite,
      probably the sulfoxide, is responsible for enzyme inactivation. The strong
      preference for omega-2 allylic or propargylic hydroxylation over terminal pi-bond
      oxidation is opposite to the usual cytochrome P450 pattern and requires that the
      enzyme actively suppress terminal pi-bond oxidation. The inference that the
      enzyme binds and sequesters the terminal carbon in a lipophilic pocket is
      consistent with the crystal structure of the hemoprotein domain of cytochrome
      P450BM-3.

PMID- 8257709
TI  - Spectroscopic evidence from site-directed mutants of Synechocystis PCC6803 in
      favor of a close interaction between histidine 189 and redox-active tyrosine 160,
      both of polypeptide D2 of the photosystem II reaction center.
AB  - The reaction center of photosystem II of oxygenic photosynthesis contains two
      redox-active tyrosines called Z and D, each of which can act as an electron donor
      to the oxidized primary electron donor, P680+. These tyrosines are located in
      homologous positions on the third transmembrane alpha-helix of each of the two
      homologous polypeptides, D1 and D2, that comprise the reaction center. Tyrosine D
      of polypeptide D2 has been proposed, upon oxidation, to give up its phenolic
      proton to a nearby basic amino acid residue, forming a neutral radical. Modeling
      studies have pointed to His190 (spinach numbering) as a likely candidate for this
      basic residue. As a test of this hypothesis, we have constructed three site
      directed mutations in the D2 polypeptide of the cyanobacterium Synechocystis sp.
      PCC6803. His189 (the Synechocystis homologue of His190 of spinach) has been
      replaced by glutamine, aspartate, or leucine. Instead of the normal D. EPR signal
      (g = 2.0046; line width 16-19 G), PSII core complexes isolated from these three
      mutants show an altered dark-stable EPR signal with a narrowed line width (11-13
      G), and g values of 2.0046, 2.0043, and 2.0042 for the His189Gln, His189Asp, and
      His189Leu mutants, respectively. Despite the reduced line width, these EPR
      signals show g values and microwave-power saturation properties similar to the
      normal D. signal. Furthermore, specific deuteration in one of those mutants at
      the 3 and 5 positions of the phenol ring of the photosystem II reaction center
      tyrosines results in a loss of hyperfine structure of the EPR signal, proving
      that the signal indeed arises from tyrosine.2+ This observation provides support
      for a model in which an imidazole nitrogen of His189 accepts the phenolic proton
      of Tyr160 upon oxidation of D, forming a back hydrogen bond to the phenolic
      oxygen of the neutral tyrosyl radical.

PMID- 8257710
TI  - Endocytosis and degradation of bovine apo- and holo-lactoferrin by isolated rat
      hepatocytes are mediated by recycling calcium-dependent binding sites.
AB  - We characterized endocytosis of iron-saturated (holo) and iron-depleted (apo)
      125I-labeled bovine lactoferrin (Lf) by isolated rat hepatocytes. Hepatocytes
      ingested both Lf forms--determined by EGTA/dextran sulfate removal of surface
      bound Lf--at maximal endocytic rates of 1.85 and 1.52 fmol cell-1 min-1 for 125I
      apo-Lf and 125I-holo-Lf, respectively. First-order endocytic rate constants (37
      degrees C) for 125I-apo-Lf and 125I-holo-Lf were 0.276 and 0.292 min-1,
      respectively. Regardless of Lf's iron content, hyperosmotic media (approximately
      500 mmol/kg) inhibited Lf uptake by approximately 90%, indicating endocytosis of
      both Lf forms was primarily clathrin-dependent. Endocytosis of both Lf forms was
      not altered significantly in the presence of excess iron chelator desferrioxamine
      or rat holo-transferrin, or by cycloheximide treatment. Fluorescein
      isothiocyanate- and cyclohexanedione-modified Lf competed fully with native Lf
      for binding and endocytosis, indicating that, unlike human Lf, modification of
      lysine or arginine residues does not block the interaction of bovine Lf with
      cells. After binding Lf at 4 degrees C, cells at 37 degrees C internalized
      approximately 90% of Lf bound to Ca(2+)-dependent sites but not Lf bound to
      Ca(2+)-independent sites. Following uptake, hepatocytes released acid-soluble
      (degraded) products of 125I-Lf biphasically at 37 degrees C, an initial rapid
      phase within the first 20 min--more pronounced with 125I-holo-Lf--followed by a
      sustained linear release of 298 and 355 molecule equiv cell-1 min-1 for 125I-apo
      Lf and 125I-holo-Lf, respectively. At 4 degrees C, both digitonin-permeabilized
      and intact cells bound approximately 1.1 x 10(6) 125I-Lf molecules to Ca(2+)
      dependent sites per cell, indicating that hepatocytes do not contain a sizeable
      intracellular pool of these sites. Moreover, cells retained > 70% of Ca(2+)
      dependent sites on the surface during sustained Lf endocytosis. Thus, these Lf
      binding sites recycle during endocytosis at an estimated 4-5 min/circuit.

PMID- 8257711
TI  - Phospholipid asymmetry of goat sperm plasma membrane during epididymal
      maturation.
AB  - The phospholipids and their fatty acids of the inner and outer plasma membrane
      leaflets of the maturing goat caput-, corpus-and cauda-epididymal spermatozoa
      were analyzed by treating the intact spermatozoa with phospholipase C and
      trinitrobenzene sulphonate. The inner and outer membrane showed marked
      differences in the phospholipid composition at all stages of epididymal sperm
      maturation. The outer membrane was rich in phosphatidylcholine (PC) and
      sphingomyelin (SPH) whereas the inner leaflet was dominated by
      phosphatidylethanolamine (PE). Although the ratio of PE/PC in the inner membrane
      was similar in both the mature cauda sperm and the immature caput sperm, it
      decreased significantly in sperm undergoing maturation in the corpus-epididymis.
      The distribution of the saturated and unsaturated fatty acids in the phospholipid
      fractions of both the membrane leaflets underwent profound alterations during the
      epididymal maturation. The data demonstrate asymmetry of phospholipids and their
      fatty acids in the sperm inner and outer plasma membranes and this lipid
      asymmetry is greatly altered during epididymal maturity of the male gametes.

PMID- 8257712
TI  - Attenuation of diacylglycerol signal in the primordial human placenta: role of
      phosphatidylcholine formation.
AB  - Metabolic conversion of the synthetic DAG, dioctanoylglycerol (DOCG) into the
      dioctanoyl species of phosphatidic acid (PADOCG) and phosphatidylcholine (PCDOCG)
      in minced human primordial placenta incubated with [32P]phosphate was studied.
      Time-course experiments performed with 0.25 mM DOCG revealed a much higher
      capacity of the placenta to synthetize PCDOCG than PADOCG and indicated the rapid
      metabolism of PCDOCG. In addition, DOCG stimulated the labeling of PC whereas no
      such effects on the labeling of lyso-PC and PA were observed. This effect of DOCG
      is not related to the synthesis of PC de novo, because DOCG did not exhibit any
      stimulating effect on the synthesis of PC from [3H]glycerol or [3H]glucose.
      Experiments with varying concentrations of DOCG (0.025-0.5 mM) showed increasing
      rate of formation of PCDOCG over a concentration range from 0.05 to 0.5 mM
      whereas 0.5 mM DOCG was the lowest concentration where significant formation of
      PADOCG was found. Labeling of PC was about 30% over control at 0.125 mM as well
      as at 0.25 mM DOCG, and decreased below the control level at 0.5 mM DOCG.
      Labeling of PA and PI was not influenced by these DOCG concentrations. Labeling
      of PC, either stimulated by DOCG or not, was more sensitive to the inhibitory
      effect of 1 mM of the DAG analog: dioctanoylethyleneglycol (DOEG) than that of
      PA. Moreover, 1 mM DOEG inhibited the formation of PCDOCG without such an effect
      on the labeling of PADOCG. These findings indicate that in the primordial human
      placenta PC synthesis represents a more efficient attenuation pathway of DAG
      signal than the formation of PA by DAG kinase.

PMID- 8257713
TI  - Lipoprotein lipases, lipoprotein density gradient profile and LDL receptor
      activity in miniature pigs fed fish oil and corn oil.
AB  - The effects of fish oil and corn oil on plasma lipoprotein concentrations, the
      lipolytic enzymes, lipoprotein lipase and hepatic triacylglycerol lipase, the
      density distribution of the plasma lipoproteins and LDL receptor activity were
      studied. These experiments were designed, in part, to define the mechanism(s)
      responsible for the increased conversion of plasma VLDL apolipoprotein B to LDL
      and a decreased LDL apolipoprotein B fractional catabolic rate described in
      previous apolipoprotein B kinetic studies. Miniature pigs were fed diets for 3 to
      6 weeks containing supplements of corn oil or fish oil as Maxepa. Triacylglycerol
      and cholesterol in plasma and VLDL were significantly reduced by the fish oil
      diet. LDL and HDL cholesterol were not significantly changed. The fish oil diet
      significantly reduced post-heparin plasma lipoprotein lipase and hepatic
      triacylglycerol lipase activities, which may be an adaptive response to the low
      concentration of substrates (triacylglycerol-rich lipoproteins) for these
      enzymes. No differences were observed in the density of VLDL, LDL or HDL as
      determined by density gradient ultracentrifugation with the fish oil diet. No
      major changes in percent lipid composition of VLDL, LDL and HDL were observed. No
      differences were found with respect to LDL uptake by J774 macrophages. Receptor
      mediated clearance of LDL in vivo, as assessed by measuring the difference in
      fractional catabolic rate of native vs. methylated LDL decreased significantly by
      17% (P < 0.032). We conclude that the increased conversion of VLDL apolipoprotein
      B to LDL in miniature pigs fed fish oil is not related to an increase in
      lipolytic enzymes or density distribution of VLDL, but may be due in part to a
      decrease in LDL receptor activity.

PMID- 8257714
TI  - Dietary palmitic acid raises plasma LDL cholesterol relative to oleic acid only
      at a high intake of cholesterol.
AB  - Using a crossover design, the effects of exchanging up to 10% dietary energy
      (%en) between oleic (18:1) and palmitic acid (16:0) on plasma lipoprotein
      metabolism was investigated in 12 normocholesterolemic cebus monkeys, both in the
      absence and presence of dietary cholesterol (0.3%, w/w). In all the purified
      diets, which contained 33%en as fat blends, myristic acid (14:0) and linoleic
      acid (18:2) were held constant at 0.3%en and 3.7%en, respectively. Cholesterol
      free diets containing either high 18:1 (19%en), roughly equivalent levels of 16:0
      and 18:1 (12 and 15%en, respectively), or a high level of 16:0 (18%en), generated
      similar values for total plasma cholesterol (TC), HDL-C and LDL-C. Plasma
      triacylglycerol concentrations (TG) were significantly higher when monkeys were
      fed the 16: 0-rich diet than when fed the 18: 1-rich diet (75 +/- 6 vs. 52 +/- 8
      mg/dl; P < 0.05). LDL and HDL kinetic parameters (assessed after simultaneous
      injection of homologous 131I-LDL and 125I-HDL) revealed no significant
      differences between the 18: 1-rich or 16: 0-rich diets. By contrast, with added
      dietary cholesterol (0.78 mg/kcal) the 16: 0-rich diet resulted in significantly
      higher TC (318 +/- 20 vs. 299 +/- 20 mg/dl; P < 0.05) and LDL-C (136 +/- 10 vs.
      117 +/- 10 mg/dl; P < 0.05) in comparison to the 18: 1-rich diet. HDL-C was
      unaffected (159 +/- 8 vs. 156 +/- 5 mg/dl), but plasma TG concentrations also
      tended to be higher (70 +/- 8 vs. 60 +/- 6 mg/dl, P < 0.08). Kinetic studies
      revealed that the higher LDL-C concentration was associated with an elevated pool
      size of LDL apo B (40 +/- 2 vs. 34 +/- 2 mg/kg body weight; P < 0.005), the
      latter attributed to decreased FCR (1.06 +/- 0.07 vs. 1.27 +/- 0.12 pools/day; P
      < 0.04) with no effect on the transport rate of LDL apo B (41 +/- 2 vs. 42 +/- 3
      mg/kg body weight per day). HDL kinetic parameters were comparable during the 16:
      0 and 18: 1 dietary periods, but dietary cholesterol caused an increase in apo A
      I pool size and transport rate without impacting FCR. In this study a palmitic
      acid-rich diet failed to alter plasma or LDL-C when compared to an oleic acid
      rich diet, unless the diet also contained cholesterol. In the latter case, 16: 0
      increased LDL-C, which reflected a decrease in the efficiency of LDL apo B
      removal.

PMID- 8257715
TI  - Circannual variation in the fatty acid composition of high-density lipoprotein
      phospholipids during acclimatization in trout.
AB  - A circannual variation in the fatty acid composition of plasma and high-density
      lipoprotein (HDL) phospholipids occurs in rainbow trout (Oncorhynchus mykiss) in
      response to seasonal alterations in environmental water temperature. The
      compensatory mechanisms employed in cold adaptation include a decrease in the
      level of saturated fatty acids and of monoenes of the oleic acid (n-9) family and
      an increase in the level of unsaturated fatty acids of the linolenic acid (n-3)
      family, especially in docosahexaenoic acid (22:6(n-3)). The present study
      demonstrates that in trout, a poikilothermic vertebrate, the weight percentage of
      22:6(n-3) in HDL phospholipids is inversely correlated (r = -0.88, P < 0.0001)
      with water temperature.

PMID- 8257716
TI  - The glycolipid of Halobacterium trapanicum.
AB  - The structural elucidation of the polar lipids in Halobacterium trapanicum is
      reported with particular emphasis on a new sulfated disaccharide derivative of
      2,3-di-O-phytanyl-sn-glycerol. The full structural designation of this glycolipid
      is 2,3-di-O-phytanyl-1-O- (mannopyranosyl-(2-sulfate)-alpha-D-1-2-glucopyranosyl
      alpha-D)-sn-glyce rol. The value of glycolipid structures in the taxonomy of
      halophilic Archaea is also discussed.

PMID- 8257717
TI  - Human apolipoprotein A-IV gene expression is modulated by members of the nuclear
      hormone receptor superfamily.
AB  - Human apolipoprotein A-IV (apo A-IV) is essentially synthesized in intestine and
      to a lower extent in liver. The presence of detectable amounts of apo A-IV
      messenger in HepG2 and Caco-2 cells enables us to study the transcription
      regulation of the gene in these cells. A main hypersensitive site to DNase I is
      detected in the DNA of HepG2 nuclei, in a region situated about 3400 base pairs
      upstream from the cap site. Transient expression experiments in HepG2, Caco-2 and
      HeLa cells indicate that HNF-4 activates the transcription of a reporter gene
      through the -3500/+67 sequence of the apo A-IV gene. This activation is repressed
      by another transcription factor, Ear3/COUP-TF. On the contrary, HNF-1, whose
      expression is controlled by HNF-4, is not involved in the regulation of the
      reporter gene transcription through the -6700/+67 genome sequence. These results
      indicate that the apo A-IV gene expression is modulated by orphan ligand members
      of the superfamily of nuclear hormone receptors.

PMID- 8257718
TI  - Phospholipase D and exocytosis of the ram sperm acrosome.
AB  - We have investigated whether phospholipase D (PLD) is involved in events leading
      to acrosomal exocytosis. Ram spermatozoa pre-labelled with [3H]alkyl
      lysophosphatidylcholine and stimulated with the ionophore A23187 (1 microM) and
      Ca2+ (3 mM) in the presence of ethanol, showed a slow time-dependent increase in
      [3H]phosphatidic acid and [3H]phosphatidylethanol (PEt), the latter being clear
      evidence of PLD activity. Unlabelled cells similarly treated underwent acrosomal
      exocytosis. However, [3H]PEt formation was inhibited by high Ca2+ concentrations,
      although such conditions result in maximal acrosomal exocytosis. Treatment with
      A23187/Ca2+ led to a fast generation of [3H]alkyl-diglyceride and an increase in
      1,2-diacylglycerol mass, which preceded [3H]PEt formation. The rises in [3H]alkyl
      diglyceride and 1,2-diacylglycerol mass took place regardless of the presence or
      absence of ethanol. Inclusion of propranolol, a phosphatidic acid
      phosphohydrolase inhibitor, did not affect the early rise of labelled or
      unlabelled 1,2-diglycerides either. Stimulation of spermatozoa with A23187/Ca2+
      in the presence of either ethanol or propranolol did not affect the occurrence of
      acrosomal exocytosis. Taken together, these results indicate that although Ca2+
      entry triggers a late activation of PLD, this enzyme is not involved in the early
      generation of diglycerides. Moreover, they suggest that PLD does not make a
      substantial contribution in events leading to exocytosis of the sperm acrosome.
      Therefore, generation of diglycerides may take place primarily via phospholipase
      C.

PMID- 8257719
TI  - Changes of n-3 and n-6 fatty acids in plasma and circulating cells of normal
      subjects, after prolonged administration of 20:5 (EPA) and 22:6 (DHA) ethyl
      esters and prolonged washout.
AB  - Eight normal volunteers (four men and four women) were treated with 3 x 1 g
      capsules of n-3 fatty acid ethyl esters for a period of 18 weeks, followed by a
      24 week washout. Fatty acids of plasma, platelets, monocytes and red blood cells
      were analyzed at 0, 6, 12 and 18 weeks of treatment and at 4, 14 and 24 weeks of
      washout. During treatment, accumulation of EPA in plasma and cells was almost
      maximal at 6 weeks, whereas that of DHA reached a peak at 18 weeks. Arachidonic
      acid declined somewhat at 12 weeks in plasma and more markedly at 18 weeks in red
      blood cells and monocytes. During washout, EPA returned rapidly toward
      pretreatment values in all compartments, but it remained significantly higher in
      plasma and platelets at the end of washout. DHA declined more slowly, maintaining
      higher than basal values in plasma and platelets and lower than basal in red
      blood cells, at the end of washout. Rebound increments of AA occurred in plasma.
      Finally, the plasma levels of AA, but not those of the n-3 fatty acids, were more
      markedly modified in males than in females. The presented results suggest
      interactions between circulating fatty acids in the different compartment after n
      3 FA administration, and indicate that very long washouts are necessary for a
      complete recovery from the induced fatty acid modifications.

PMID- 8257720
TI  - Endocytosed LDL and beta-VLDL follow different intracellular pathways in rat
      liver.
AB  - The intracellular transport of [125I]tyramine cellobiose low-density lipoprotein
      ([125ITC]LDL) and [131ITC]beta-very-low-density lipoprotein ([131ITC]beta-VLDL)
      in rat liver was studied by means of centrifugation in sucrose and Nycodenz
      gradients. At time-points up to 45 min after intravenous injection, the two
      ligands were found in endosomes with distinctly different buoyant densities. In
      the Nycodenz gradients [131ITC]beta-VLDL appeared at 1.08 g/ml partly coinciding
      with the distribution of the cation independent (alpha)mannose-6-phosphate
      receptor, whereas [125ITC]LDL was found at 1.13 mg/ml, where the degradation of
      [125ITC]LDL started. [131ITC]beta-VLDL, on the other hand, was transferred to
      denser vesicles, banding at 1.16 g/ml, and degradation started in these
      organelles, similar to that observed with asialoorosomucoid (ASOR) that was used
      as a control ligand. Since degradation products coincided with beta-N
      acetylglucosaminidase we assume that these organelles are secondary lysosomes.
      [125ITC]LDL was subsequently also transferred to these dense secondary lysosomes,
      and the distribution of degraded [125ITC]LDL was therefore bimodal until
      [125ITC]LDL was completely cleared from the circulation. Furthermore our results
      show that the different intracellular pathways observed are not due to uptake in
      different liver cell types, since the bimodal distribution of [125ITC]LDL was
      also evident in purified liver parenchymal cells. The data suggest that LDL and
      beta-VLDL follow different endosomal pathways in the rat hepatocytes and that
      both pathways meet in a common final lysosome. The data also support the notion
      that LDL and beta-VLDL are taken up through different endocytic receptors.
      However, following estradiol treatment, both ligands seem to follow a common
      pathway. In this case the density distributions of the two ligands coincide and
      resemble the pathway of LDL observed in control animals. This may be due to a
      pronounced up-regulation of LDL receptors following estradiol treatment, and beta
      VLDL may under these conditions be taken up via the LDL receptor.

PMID- 8257721
TI  - Bile acid synthesis in hamster hepatocytes in primary culture: sources of
      cholesterol and comparison with other species.
AB  - The synthesis of bile acids by primary hamster hepatocytes in culture has been
      studied. Measurable rates of bile acid synthesis were obtained from cells
      prepared from livers of animals fed 2% w/w cholestyramine to induce the synthesis
      of bile acids through the rate-limiting enzyme cholesterol 7 alpha-hydroxylase.
      The effects of various sources of substrate for bile acid synthesis in these
      cultured cells were examined over a period of 24 h and the results compared with
      published or parallel studies in primary rat hepatocytes or in the human hepatoma
      cell line, HepG2. In all the cells, bile acid synthesis was stimulated by the
      addition of 7 alpha-hydroxycholesterol, indicating the rate-limiting role of the
      cholesterol 7 alpha-hydroxylase. Bile acid synthesis in the hamster hepatocytes
      was also stimulated by a variety of sources of cholesterol as substrate,
      mevalonic acid (increasing the production of newly-synthesised cholesterol in the
      cell), and as an exogenous source, hamster LDL. Similarly, if cholesterol was
      diverted from intracellular esterification using the ACAT inhibitor Dup128, a
      further increase in bile acid synthesis could be demonstrated. These results show
      that hepatocytes obtained from cholestyramine-treated hamsters are deficient in
      substrate cholesterol for bile acid synthesis. A similar conclusion can be drawn
      from the published work with rat hepatocytes and is further supported by
      experiments on the regulation of cholesterol 7 alpha-hydroxylase activity at the
      mRNA and the protein level, although some in vivo studies in animals and studies
      in man have led authors to suggest that cholesterol 7 alpha-hydroxylase is
      saturated with substrate.

PMID- 8257722
TI  - Dietary lipids induce phase 2 enzymes in rat small intestine.
AB  - We examined the role of dietary lipids in determining the activities of
      glutathione S-transferase (GST) and UDPglucuronosyl-transferase (UGT) in rat
      small intestine. Male Wistar rats were fed a fat-free (FF) diet or isocaloric
      control diet containing 5% corn oil (CO) or 5% fish oil (FO) for 3 weeks. The
      activities of these enzymes were about 2-fold higher in rats fed the FO diet vs.
      the FF diet. Intermediate levels of enzyme activity were found in rats fed the CO
      diet. Diet-induced differences in enzyme levels were shown by immunoblotting. The
      highest levels of glutathione S-transferase and UDPglucuronosyltransferase were
      detected in rats fed the FO diet. The lowest levels of these enzymes were found
      in rats fed the FF diet. Intermediate levels of enzyme were detected in rats fed
      the CO diet. Thus, diet-induced differences in enzyme activities were paralleled
      by changes in enzyme levels. Fatty acid analysis of mucosal lipids showed that
      the FF and FO diets were associated with decreased levels of linoleic and
      arachidonic acids as compared with the CO diet.

PMID- 8257723
TI  - Effects of metal chelating agents on the oxidation of lipids induced by copper
      and iron.
AB  - The non-enzymatic oxidations of soybean phosphatidylcholine liposomes, methyl
      linoleate micelles and low-density lipoprotein in aqueous dispersions induced by
      copper and iron have been studied aiming specifically at elucidating the action
      of the metal chelating agents such as ethylenediaminetetraacetic acid disodium
      salt (EDTA), nitrilotriacetic acid (NTA), adenosine-5'-diphosphate disodium salt
      (ADP), desferrioxamine (DFO), penicillamine (PCM), and triethylene tetramine
      (TTM). The effects of chelators on chemiluminescence emitted from its probe
      luminol in the decomposition of tert-butyl hydroperoxide by metal ion were also
      studied. The effects of chelators on the oxidations depended both on the metal
      ion and the substrate. Namely, in the oxidations of both liposomes and micelles,
      EDTA and NTA suppressed the copper-induced oxidations, whereas they enhanced the
      oxidations induced by iron. ADP had little effect, while PCM and TTM had
      accelerating effect for both metal ions. On the other hand, in the oxidation of
      LDL, none of these chelators enhanced the oxidation. Especially, TTM and PCM
      suppressed the copper-induced oxidation of LDL, suggesting that the chelating
      agents blocked the access of the metal ion to the hydroperoxide within LDL. The
      effects of chelators on chemiluminescence emission were similar to those on the
      oxidations of liposomes and micelles. The cyclic voltammograms of metal complexes
      were also measured. The multiple effects of chelators on the rate of non
      enzymatic, metal-catalyzed oxidations of lipids were interpreted by their
      influence on redox-potential and accessibility to hydroperoxide of the metal
      chelator complex.

PMID- 8257724
TI  - Purified dietary n-3 polyunsaturated fatty acids alter diacylglycerol mass and
      molecular species composition in concanavalin A-stimulated murine splenocytes.
AB  - A low-dose, short-term dietary supplementation with highly purified (n-3) fatty
      acid ethyl esters was studied in mice to determine the effect on splenic cell
      membrane diacylglycerol mass and composition. Mice were fed diets containing
      either 3% safflower oil (SAF) ethyl esters, 2% SAF plus 1% eicosapentaenoic acid
      ethyl ester (EPA), or 2% SAF plus 1% docosahexaenoic acid ethyl ester (DHA).
      Following a 10-day feeding period, pathogen-free mice were sacrificed and splenic
      cells isolated and stimulated with concanavalin A (Con A) at 10 micrograms/ml.
      After 0 min (basal), 5 min, and 180 min, 1,2-diacyl, 1-O-alkyl-2-acyl, and 1-O
      alkenyl-2-acyl-sn-glycerol subclasses were isolated and quantitated by HPLC.
      Diacylglycerol (DAG) was found to be the major diradylglycerol (DG) component in
      murine splenocytes. DHA-fed mice had significantly (P < 0.05) higher levels of
      DAG at all stimulation time points relative to EPA and SAF animals. Significant
      effects (P < 0.05) of diet, time, and a diet x time interaction (P < 0.05) were
      noted for various DAG molecular species. In general, a significantly higher (n-3)
      polyunsaturated fatty acid (PUFA) content in the EPA and DHA groups, and a
      significantly higher (n-6) PUFA content in the SAF group was noted. 18:0-22:5(n
      3), 18:1-22:5(n-3) and 16:1-20:5(n-3) species were present only in EPA and DHA
      DAG, confirming the incorporation of (n-3) fatty acids into splenocyte DAG. The
      data indicate that the molecular species composition of murine splenocyte DAG is
      significantly modulated by low-dose, short-term EPA and DHA feeding. In addition,
      substitution of SAF with DHA results in an increase in DAG mass. These
      alterations could potentially influence signal transduction pathways regulating
      lymphocyte function.

PMID- 8257725
TI  - Sphingosine inhibits sphingomyelinase-induced cholesteryl ester formation in
      cultured fibroblasts.
AB  - We have in this study examined the effects of sphingosine, a possible secondary
      degradation product following sphingomyelin hydrolysis, on cholesterol
      homeostasis in cultured human fibroblasts treated with sphingomyelinase. The
      activation of cholesterol esterification, which resulted from the degradation of
      plasma membrane sphingomyelin (by sphingomyelinase), was observed to be
      effectively blocked by sphingosine (half-maximal dose 6-7 microM). The inhibitory
      action of sphingosine could not be reproduced with other amines (e.g., dodecyl
      amine or imipramine). The onset of inhibition of cholesteryl ester formation by
      sphingosine was rapid (maximal effect within 15 min). Sphingosine itself had no
      spontaneous effects on the distribution of cellular cholesterol. At
      concentrations below 10 microM, sphingosine was not cytotoxic, as determined by
      cellular trypan blue permeability. The inhibitory action of sphingosine on
      cholesteryl ester formation apparently did not result from a direct inhibition of
      acyl-CoA cholesterol acyltransferase (ACAT), since the activity of this enzyme
      was unaffected by sphingosine (10 microM) in a cell-free homogenate, using
      [14C]oleoyl-CoA as a co-substrate. Sphingosine was also unable to prevent the
      formation of activated fatty acids (oleoyl-CoA), since acyl-CoA synthetase
      activity in a cell-free homogenate was not inhibited by sphingosine (at 5
      microM). The cellular cholesteryl ester cycle (i.e., the neutral cholesteryl
      ester hydrolase) was unaffected by sphingosine (at 5 microM). Down-regulation of
      PKC activity (24 h exposure of cells to 100 nM (62 ng/ml) phorbol ester) did not
      affect the sphingomyelinase-induced stimulation of [3H]cholesteryl ester
      formation. In addition, the sphingosine-induced inhibition of [3H]cholesteryl
      ester formation was not reversed in the presence of phorbol ester (short-term
      exposures), suggesting that the effect of sphingosine was not mediated via PKC.
      In conclusion, we have shown that sphingosine is an inhibitor of cholesteryl
      ester formation in fibroblasts. The inhibition is only seen with intact cells,
      which may suggest that a secondary metabolite of sphingosine was responsible for
      the observed inhibition of cholesteryl ester formation.

PMID- 8257726
TI  - Quantitative 1H-NMR analysis of amniotic fluid.
AB  - Ten amniotic fluid samples (36-38 weeks gestation) are analysed by NMR
      spectroscopy. Of the species identified in the spectra, valine (mean 198 microM:
      SEM 57 microM), lactate (9.73 mM; 2.05 mM), alanine (689 microM: 115 microM),
      acetate (6.87 mM: 1.54 mM), citrate (363 microM: 59 microM), glucose (4.54 mM:
      1.28 mM) indoxyl-sulphate (n = 4,270 microM), histidine (n = 6, 125 microM: 31
      microM) and formate (n = 4, 92 microM) are quantified using standard addition.
      The factors governing the detection limits and lowest quantifiable amounts are
      discussed as are the extension of the work into in vivo magnetic resonance
      spectroscopy (MRS) in the clinic.

PMID- 8257727
TI  - Determination of penicillamine or tiopronin in pharmaceutical preparations by
      flow injection analysis.
AB  - Two flow injection analysis (FIA) methods, using spectrophotometric detection,
      are proposed for the determination of penicillamine or tiopronin [N-(2
      mercaptopropionylglycine)]. The procedures are based on the formation of yellow
      complexes between these thiol-containing drugs and Pd(II), in a 1 M or 0.25 M HCl
      medium, respectively. With peak height as a quantitative parameter, penicillamine
      is determined over the range 1.0 x 10(-5)-7.0 x 10(-4) M; for tiopronin the range
      is 1.0 x 10(-5)-6.0 x 10(-4) M. The methods have been applied to the routine
      determination of the drugs in pharmaceutical preparations.

PMID- 8257728
TI  - Spectrophotometric analysis of some guanidino drugs by acid-dye and charge
      transfer complexation methods.
AB  - Two spectrophotometric methods are described for the determination of
      guanethidine sulphate (I), guanfacine hydrochloride (II), guanoclor sulphate
      (III), guanoxan sulphate (IV) and debrisoquine sulphate (V). The first method
      involves ion-pair formation of the selected compounds (I-V) with bromocresol
      purple at pH 3.8. The yellow ion pair is extracted with chloroform and the
      absorbance is measured at about 415 nm. The second method is based on the
      reaction of the basic guanidino compounds (I, III-V) with iodine in chloroform to
      give molecular charge-transfer complexes with maximum absorbance at 292 and 345
      nm. Beer's law was obeyed for both methods and the relative standard deviations
      were found to be less than 2%. The apparent molar absorptivities were found to be
      2.1 x 10(4) to 6.9 x 10(4) l mol-1 cm-1 using bromocresol purple and 0.7 x 10(4)
      to 2.4 x 10(4) l mol-1 cm-1 using iodine. The investigated drugs were assayed in
      tablets. The mean percentage recoveries were found to be 99.8-100.8% by the acid
      dye method and around 100.4% by the charge-transfer complexation method.

PMID- 8257729
TI  - Spectrophotometric determination of dihydralazine in pharmaceuticals after
      derivatization with 2-hydroxy-1-naphthaldehyde.
AB  - A sensitive and selective colorimetric assay has been developed for the
      determination of dihydralazine. The method is based on the interaction of
      dihydralazine with an ethanolic solution of 2-hydroxy-1-naphthaldehyde to yield a
      water-insoluble yellow product, 1,4-bis[(2-hydroxy-1-naphthyl)methylene
      hydrazine]phthazine. This colour can be quantified spectrophotometrically at 420
      nm. The calibration curve was linear between 0.4 and 8 micrograms ml-1 of
      dihydralazine. The molar absorptivity at 420 nm is 24000 l mol-1 cm-1. The method
      was successfully applied to the determination of dihydralazine in mixtures
      containing other drugs (reserpine, hydrochlorothiazide, oxprenolol, xanthinol,
      rutoside, chlorthalidone and bietaserpine).

PMID- 8257730
TI  - 600 MHz 1H-NMR spectroscopy of human cerebrospinal fluid: effects of sample
      manipulation and assignment of resonances.
AB  - Extensive assignments of resonances in the 600 MHz 1H-NMR spectra of
      cerebrospinal fluid are reported. These have been achieved by the measurement of
      a combination of two-dimensional experiments comprising homonuclear J-resolved,
      COSY45, and double-quantum filtered COSY (DQCOSY) spectra. By these means the
      previous total of 18 endogenous metabolites, of which in general only selected
      resonances have been assigned, has been augmented to 46 molecules including all
      of the resonances of both alpha- and beta-anomers of glucose. With only a few
      exceptions all resonances have been assigned for all of the metabolites. In
      addition, the effect of freeze-drying on the 600 MHz 1H-NMR spectrum of human
      cerebrospinal fluid (CSF) is presented using both lyophilization with
      reconstitution into either H2O or D2O. Freeze-drying and reconstitution into H2O
      causes a significant sharpening of many small molecule resonances, including
      notably those of glutamate and glutamine as well as other amino acids and in
      addition causes the loss of volatile components, principally acetone. Further
      exchange of the H2O solvent by D2O causes no additional changes in the spectra.

PMID- 8257731
TI  - Determination of the optical purity and absolute configuration of threo
      methylphenidate by proton nuclear magnetic resonance spectroscopy with chiral
      solvating agent.
AB  - The direct determination of both the optical purity and absolute configuration of
      threo-methylphenidate has been accomplished in a simple, specific, and accurate
      manner by 1H-NMR spectroscopy. The enantiomeric resonances of threo
      methylphenidate were effectively resolved in CDCl3 solution by the addition of
      the chiral solvating agents (R)-(-)- or (S)-(+)-2,2,2,-trifluoro-1-(9
      anthryl)ethanol. Optical purities were determined on the basis of the intensities
      of the enantiomeric ester methyl proton resonances; the assignment of
      enantiomeric configurations was based on the relative field positions of these
      resonances and the examination of molecular models. The analysis of synthetic
      enantiomeric mixtures of threo-methylphenidate by the proposed NMR method
      resulted in assay values that agreed closely with the known quantities of each
      enantiomer in the mixtures tested. The mean +/- SD recovery value for the
      (2S,2'S)-(-)-threo-enantiomer, amounting to 99.9 +/- 0.6% of added (n = 10),
      correlated well with that previously found by 1H-NMR spectroscopy with a chiral
      Eu(III) shift reagent. However, the present approach is simpler, shows less
      reliance on reagents and solvents of a high purity, and does not require strict
      anaerobic working conditions.

PMID- 8257732
TI  - Deuterium NMR spectroscopy of biofluids for the identification of drug
      metabolites: application to N,N-dimethylformamide.
AB  - The metabolism of N,N-dimethylformamide in the Sprague-Dawley rat has been
      reinvestigated using NMR spectroscopy of urine. In particular, through the use of
      N,N-dimethylformamide-d7 (DMF-d7) and 2H-NMR spectroscopy, the principal
      metabolites of this compound have been confirmed in a direct manner. The use of
      inverse-detected two-dimensional 2H-13C correlation with 13C decoupling aided
      metabolite identification through the provision of 13C chemical shifts.

PMID- 8257733
TI  - Challenging declarations of abstinence by the determination of morphine in hair
      by radioimmunoassay.
AB  - Morphine extracted from dated hair segments and analysed by adaptation of a
      specific solid-phase 125I radioimmunoassay for the measurement of morphine in
      urine has provided long term histories of the heroin usage of individual
      patients. Results expressed as ng morphine/mg hair are compared with a pre
      determined cut-off level of 0.3 ng morphine/mg hair, from a known drug-free
      population (n = 21). Morphine concentrations in hair samples from known heroin
      abusers are found to be above the cut-off limit (range 0.6-9.4 ng morphine/mg
      hair), and suggest a possible correlation between heroin intake and concentration
      of morphine in hair. Intra-assay relative standard deviation (RSD), at morphine
      levels of 9.27 and 1.12 ng morphine/mg hair are 2.4 and 5.5%, respectively, and
      acceptable recoveries from drug-free hair spiked with morphine are also achieved.
      The developed segmental hair analysis regime has been used successfully to
      challenge a self-declaration of heroin abstinence. Routine cumulative urine
      screening was unable to provide such evidence. The potential for hair drug
      analysis is discussed.

PMID- 8257734
TI  - Determination of amantadine in human plasma by capillary gas chromatography using
      electron-capture detection following derivatization with pentafluorobenzoyl
      chloride.
AB  - A specific, sensitive, and accurate capillary gas chromatographic method for the
      quantitation of amantadine in human plasma is described. Amantadine and the
      internal standard, rimantadine were extracted from plasma under alkaline
      conditions into toluene. Both compounds were derivatized with pentafluorobenzoyl
      chloride. The derivatives were separated on a HP-1 capillary column at 180
      degrees C and detected using a 63Ni electron-capture detector. The minimum
      quantifiable limit of the assay is 2.3 ng ml-1 of amantadine base using 1 ml of
      plasma. The method was used to evaluate the bioequivalence of two different
      formulations of amantadine hydrochloride.

PMID- 8257735
TI  - The development and application of coupled HPLC-TLC for pharmaceutical analysis.
AB  - Successful coupling of high-performance liquid chromatography (HPLC) and thin
      layer chromatography (TLC) facilitates correlation of the retention factor (Rf)
      of a component in a TLC separation with a peak observed in HPLC, thus eliminating
      the need for isolation of the component. Experiments were designed to optimize
      flow and spotting rates for typical HPLC mobile phases, evaluating such
      parameters as band broadening and on-plate loading. Also investigated were the
      application of flow splitting and semi-microbore HPLC columns. The problems
      encountered with the development of TLC plates upon which the HPLC eluent has
      been applied as a linear streak were studied, as were detection methods for the
      resulting spots. This paper describes the successful development of the
      technique, using model compounds of pharmaceutical interest.

PMID- 8257736
TI  - A micellar liquid chromatographic procedure for the determination of amiloride,
      bendroflumethiazide, chlorthalidone, spironolactone and triamterene in
      pharmaceuticals.
AB  - A procedure for the determination of amiloride, bendroflumethiazide,
      chlorthalidone, spironolactone and triamterene in pharmaceutical preparations
      (tablets) by micellar liquid chromatography, using a 0.07 M SDS-0.5% pentanol
      mobile phase, is proposed. Recoveries were found in the 100-108% range, with
      relative standard deviations of 0.4-3.1%. Elution of the most retained diuretics
      occurred in less than 18 min (at a 1 ml min-1 flow rate). The change in the
      values of the solute-micelle binding constants and the partition coefficients of
      the diuretics between the stationary phase and water, upon addition of pentanol,
      was also studied.

PMID- 8257737
TI  - The suitability of carboplatin solutions for 14-day continuous infusion by
      ambulatory pump: an HPLC-dynamic FAB study.
AB  - The stability of aqueous carboplatin solutions over 14 days has been studied at
      37 and 60 degrees C. High-performance liquid chromatography and dynamic FAB mass
      spectrometry studies have shown that carboplatin solutions were stable at 37
      degrees C but degraded at 60 degrees C. Fluid loss through evaporation was
      significant at the higher temperature.

PMID- 8257738
TI  - The use of ultraviolet spectra and chromatographic retention data as an aid to
      metabolite identification.
AB  - Phenoxypropanolamines and their putative 4-hydroxy metabolites have been
      chromatographed using reversed-phase HPLC and UV spectra recorded using a linear
      diode array detector. Analysis of the chromatographic data using the functional
      group contribution approach allowed peaks to be tentatively characterized as
      hydroxy metabolites. This characterization was further enhanced by the
      examination of the UV spectra which showed distinct changes following
      hydroxylation. Used in combination, the two techniques allow discrimination
      between the possible isomeric hydroxy metabolites. The chromatographic and
      spectral changes observed with the relatively complex phenoxypropanolamines can
      be successfully modelled using simple compounds to further facilitate
      identification.

PMID- 8257739
TI  - RP-HPLC peptide mapping methods for the analysis of recombinant human pro
      urokinase.
AB  - Among the techniques available for the detection of protein structure variants
      such as single point mutations, RP-HPLC peptide mapping plays a key role owing to
      the high reproducibility of peptide retention times, determined as identity
      indexes. Because of the possible co-elution of some proteolytic fragments, an
      improvement of the array of information given by the technique can be achieved by
      setting up a series of experiments under hydrolytic conditions with different
      enzymes, followed by appropriate RP-HPLC gradient elutions. Such an experimental
      approach appears to be particularly useful in the examination of proteins with a
      high molecular weight, where the resulting RP-HPLC maps are complex. Therefore
      different RP-HPLC peptide mapping methods have been studied for recombinant human
      pro-urokinase (r-h-proUK), a thrombolytic agent of apparent molecular weight of
      46 kD. The RP-HPLC maps indicate that the methods developed are not only suitable
      for the qualitative control of the amino acid sequence and arrangement of
      disulphide bonds but also represent the first demonstration of the identity of
      the primary structure of the recombinant and of the native species, within the
      limits of the technique.

PMID- 8257740
TI  - Determination of debrisoquine and 4-hydroxydebrisoquine in urine by high
      performance liquid chromatography with fluorescence detection after solid-phase
      extraction.
AB  - A simple, selective and sensitive method has been developed to determine
      debrisoquine and 4-hydroxydebrisoquine in human urine. Separation of the analytes
      was obtained using a mobile phase of 0.1 M sodium dihydrogen phosphate
      acetonitrile (87:13, v/v) and a muBondapak C18 column. The column effluent was
      monitored with fluorescence detection at 210 nm (ex) and 290 nm (em). Rapid
      sample preparation was achieved by solid-phase extraction columns (Bond Elut CBA,
      3 ml capacity) which provided excellent recovery values for both compounds. The
      cost per sample using this approach could be minimized by column regeneration and
      re-use. The within-day and the day-to-day reproducibilities were less than 7% for
      both components. The method was shown to be suitable for the study of the
      debrisoquine-sparteine type genetic polymorphism in man.

PMID- 8257741
TI  - HPLC study of the impurities present in different ursodeoxycholic acid
      preparations: comparative evaluation of four detectors.
AB  - The use of HPLC with different detectors has been investigated for the analysis
      of bile acid impurities present in four different commercially available
      ursodeoxycholic acid preparations. The bile acids were efficiently separated by
      C18 reversed-phase HPLC using methanol-water (3:2, v/v) as the mobile phase. The
      detectors used for bile acid detection were: UV at 200 nm refractive index (RI)
      and an evaporative light scattering mass detector (ELSD II). A prederivatization
      method with the formation of a fluorescent naphthacyl ester has also been used.
      GC-MS analysis of Me-TMS bile acid derivatives was included as a reference
      method. The four ursodeoxycholic acid samples were 98-99% pure. The main
      impurities present in the samples were chenodeoxycholic acid and to a lesser
      extent lithocholic acid. Only one sample was found to be almost 100% pure using
      all the detectors. Significant agreement of the data was found between RI, ELSD
      II detectors and the fluorescent method; the UV detector was unsuitable for use
      in this method. The analytical performances of the four detectors for bile acid
      analysis are reported and discussed. When the four-detector data were compared
      with the GC-MS method, reasonable agreement resulted. Discordant results were
      found in the quantitation of trace impurities like lithocholic acid and/or other
      minor bile acids present in amounts less than 0.1%.

PMID- 8257742
TI  - HPLC-fluorescence determination of bile acids in pharmaceuticals and bile after
      derivatization with 2-bromoacetyl-6-methoxynaphthalene.
AB  - 2-Bromoacetyl-6-methoxynaphthalene was used as a pre-chromatographic fluorescent
      labelling reagent for the high-performance liquid chromatographic (HPLC) analysis
      of bile acids. The derivatization reaction was performed in an aqueous medium in
      the presence of tetrahexylammonium bromide by ultrasonication at 40 degrees C to
      give fluorescent esters which were separated by reversed-phase HPLC and detected
      fluorimetrically (lambda ex = 300 nm, lambda em = 460 nm). Applications to the
      determination of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) in
      their pharmaceutical formulations are described. The method was also applied to
      the determination of free and conjugated bile acids in human bile samples.

PMID- 8257743
TI  - The determination of bromazepam in plasma by reversed-phase high-performance
      liquid chromatography.
AB  - A reversed-phase high-performance liquid chromatographic method has been
      developed for the determination of bromazepam, an anxiolytic benzodiazepine, in
      plasma. After a single-step extraction from alkalinized plasma with diethyl-ether
      in the presence of an internal standard (alpha-hydroxy-triazolam), the residues
      were chromatographed on a reversed-phase Nova Pak 5 microns C18 column, with a
      mobile phase of acetonitrile-water-triethylamine (700:300:4, v/v/v) adjusted to
      pH 7.4 with orthophosphoric acid. The limit of detection was 50 ng ml-1, using a
      20 microliters injection with UV detection at 240 nm. Between-day and within-day
      relative standard deviations were lower than 6%. Studies of drug stability during
      sample storage at -20 degrees C and at +4 degrees C showed no degradation of
      bromazepam. However, bromazepam seemed to be degraded at ambient temperature,
      without any influence of light. This method is applied to the determination of
      bromazepam plasma levels in analytical toxicology.

PMID- 8257744
TI  - Fluorimetric determination of tauromustine (a novel antitumour agent) in
      formulations and biological fluids.

PMID- 8257745
TI  - Quantitative determination of ambroxol hydrochloride in tablets.

PMID- 8257746
TI  - [Maintaining professional competence of the family doctor: recertification and
      accreditation].

PMID- 8257747
TI  - [Diagnosis and control of hypercholesterolemia: implications in clinical
      practice].

PMID- 8257748
TI  - [Acceptability, reliability and validity of the Corney and Clare social problems
      questionnaire].
AB  - OBJECTIVE: To evaluate the acceptability, reliability and concurrent validity of
      the CORNEY and CLARE self-administered social problems questionnaire. DESIGN:
      Reliability was studied by a test-retest (24 hours). Validity (concordance) was
      studied through comparison with a standard social adaptation interview. SETTING:
      Primary Health Care. PATIENTS: Consecutive patients attached to a long-treatment
      nursing station and 4 medical clinics. MEASUREMENTS AND MAIN RESULTS: The
      questionnaire consisted of 33 items and evaluated 9 areas of social functioning.
      In each area, the items covered 2 types of evaluation: problems in objective
      circumstances or in functioning and level of satisfaction. There were no
      significant difficulties in the questionnaire's administration. In the test
      retest evaluation, there was adequate concordance of the average scores of the
      items evaluating difficulties and problems. This was not the case for the average
      scores of the items which evaluated satisfaction. The validity of 28 of the
      questionnaire's 33 items was examined. A moderate concordance level was found for
      11 items on the questionnaire. An average score taken from these items provided a
      sufficient measurement of tendency regarding the overall seriousness of the
      subjects' social problems. CONCLUSIONS: The results do not favour the use of this
      questionnaire as a substitute for standard interviews in the evaluation of
      specific social problems, but do support the use of part of it in order to obtain
      a valid tendency measurement.

PMID- 8257749
TI  - [Knowledge and attitudes of practice of health workers in Bizkaia health centers
      toward diet and cholesterol].
AB  - OBJECTIVE: Analyze the extent to which criteria and practice of the Sanitary
      Personnel approximate the recommendations of the Consensus on the Control of
      Hypercholesterolemia in Spain, find out how extensive their dietary knowledge in
      and how skillful they are to interview and counsel a patient with hyperlipidemia.
      DESIGN: Transversal study with simple aleatory sampling using a questionnaire.
      PARTICIPANTS AND LOCATION: 101 physicians and 95 nurses working in Primary Health
      Care Teams in Bizkaia, during the monthly of June 1991; deputies for periods
      inferior to 3 months were excluded. MEASUREMENTS AND MAIN RESULTS: 82% of
      physicians (P) counselled dietetic treatment for cholesterolemic levels
      coinciding with those set in the Consensus and 70% demanded excessive analytical
      controls for hypercholesterolemic patients under treatment already normalized;
      37% (P) and 12% of nurses (N) knew that the polyunsaturated/saturated fat ratio
      is the main dietetic factor; various errors were detected in questions relating
      to olive oil, unsaturated fat in fish and fibre values of legume; accurate
      responses between 13-54% (N) and 23-77% (P). CONCLUSIONS: The "mediterranean
      diet" is not sufficiently known; our ability for the dietetic interview and
      personalized counsel needs to be improved. In the light of the above and taking
      into accounted the gaps and deviations existing between our practice and the
      Consensus and its applications, we consider a better diffusion of the cited
      document is necessary among Primary Health Care Teams.

PMID- 8257751
TI  - [Who prescribes? Origin and adequacy of long term prescriptions included in a
      computerized long term treatment programme at a health center].
AB  - OBJECTIVE: To quantify medications not prescribed at the primary level and their
      suitability for patients included in a programme of compliance and computerised
      control of long treatments at a Health Centre. DESIGN: Descriptive study.
      SETTING: Zumaia Health Centre (Guipuzcoa). PATIENTS: The study sampled 75
      patients out of a total of 397 in treatment. MEASUREMENTS AND MAIN RESULTS: The
      total number of drugs studied was 230, out of which 23% were prescribed by the
      General Practitioner and 77% referred from other care levels. Of these last, the
      bibliographical sources consulted advised against their use in chronic treatments
      in one out of every 5 cases, which depended on the pathology which was the cause
      of referral. CONCLUSIONS: Much of the medication included in our long-treatment
      programme was prescribed at other care levels than our Health Centre. The
      elaboration of a list of medications excluded from long-treatment programmes
      should bear in mind the prescription's real origin in order to avoid negative
      consequences both for the user and the system. The computerisation of
      prescriptions could be extremely valuable both in the control of our programmes
      and the analysis of their attributable costs. We propose that the validity of the
      type of referred medications used for long-treatment patients should be studied
      as an indicator of a Health Centre's proper functioning.

PMID- 8257750
TI  - [Results of 5 campaigns to detect previously unidentified cases of hypertension].
AB  - OBJECTIVE: To find the efficacy of two methods of detecting previously unknown
      hypertension--systematic taking of blood pressure (ST) and the Mobile Unit (MU)-
      and to evaluate the over-diagnosis of arterial hypertension (AHT) in crossover
      studies which only use epidemiological criteria (EC). DESIGN: A descriptive study
      with population and opportunist strategies. An operative MU team attended
      commercial and work centres within the chosen area. ST looked for AHT in patients
      attending Health Centre clinics. INTERVENTION: EC in screening, in line with WHO
      guidelines and clinical confirmation (CC) in the Health Centres. SETTING: MU in
      the catchment areas of Novelda, Carrus and C. Jardin Health areas. ST in the San
      Miguel de Salinas and C. Jardin Health Centres. PATIENTS: 1654 people over 19
      with the MU and 4138 through ST. RESULTS: Both methods discovered more
      hypertension in men (MU p = 0.009 and ST p = 0.000) and in the 20 to 39 age group
      (MU p = 0.000 and ST p = 0.000). EC led to over-diagnosis (5.8% MU and 6.3% ST);
      greater in men (6.6% and 6.5%) and +/- 60 years old (8.7% and 7.5%). Positive
      predictive values obtained were 59.8% with MU and 47.4% with ST. CONCLUSIONS:
      Both methods are useful ways of identifying people suffering hypertension: both
      young people and men. But CC is essential in order to make a real diagnosis of
      AHT. Out of every 10 people detected by using EC, only 5 were confirmed by ST and
      6 by MU. This information must be borne in mind when evaluating the the
      prevalence of AHT in epidemiological studies.

PMID- 8257752
TI  - [Patients' adherence to therapy and their understanding of hypertension at health
      centers].
AB  - OBJECTIVE: The main aim was to find the prevalence of therapy adherence by means
      of self-reporting, therapy aims and its association to determined variables.
      Secondary aims were to evaluate the Morisky test and assess the patients'
      understanding of hypertension. DESIGN: A descriptive crossover study using
      questionnaires and stratified random sampling. SETTING: Nursing stations (NS) at
      a rural teaching Health Centre. PATIENTS: A sample of 122 hypertense patients,
      who were not diabetic, were treated pharmacologically, were over 25 and had
      attended the NS for at least 6 months. MEASUREMENTS AND MAIN RESULTS: 64.8%
      prevalence of adherence (CI 0.558 p < = 0.738). 99% were very satisfied with
      their relationship to the nursing staff, although their understanding of AHT was
      very low. 12% were wrongly diagnosed or over-prescribed. No statistical
      significance was found between adherence by self-reporting and the independent
      variables, but it was between adherence by control and the number of doses: p <
      0.05, OR = 0.22, CI 0.8; 0.05. Those patients with three doses had worse control
      than those with one. Test sensitivity = 0.843; Specificity = 0.16. CONCLUSIONS: A
      profile of the patient adhering to treatment could not be defined: the adherence
      rate was situated at the upper limit of other studies. The AHT procedure should
      have been checked in order to bring into line diagnosis and treatment criteria
      and to implement special adherence measures in those patients with over two daily
      doses. There was no evidence that adherence improved in line with time spent at
      the NS. The test did not predict adherence with accuracy.

PMID- 8257753
TI  - [Metabolic improvement of diabetes mellitus through pamphlets on the norms of
      self-monitoring control measures].
AB  - OBJECTIVE: To assess whether giving a leaflet containing norms of self-control to
      diabetics receiving insulin treatment results in a metabolic improvement. The
      HbA1c was established prior and subsequent to giving out the leaflet. The written
      norms contained in the leaflet were highlighted from the wider range of
      instructions obtained from diabetes education. DESIGN: A longitudinal
      intervention study with no random allocation. SETTING: Hospital care in a
      specialised Endocrinology clinic. PATIENTS AND OTHER PARTICIPANTS: 122 types 1
      and 2 diabetics, treated with various insulin diets, who had received prior
      diabetes education and carried out blood self-controls. Cases of meta-diabetic
      syndrome, serious illnesses and those without apparent hypoglycaemia symptoms
      were excluded. INTERVENTIONS: Giving out of a leaflet with written norms of self
      control. MEASUREMENTS AND MAIN RESULTS: The averages, standard deviations and 95%
      confidence intervals of the basal HbA1c and of those at four-monthly check-ups
      were calculated. Basal 8.07 (CI 7.75 - 8.39); 4th month 6.88 (CI 6.74 - 7.17);
      8th month 6.59 CI 6.29 - 6.90); 12th month 6.60 (CI 6.23 - 6.94); 16th month 6.06
      (CI 5.63 - 6.49); 20th month 5.40 (CI 3.04 - 7.75). Averages were compared by the
      Student T test and all values had p < 0.005 against the basal. CONCLUSIONS:
      Following the written norms produced a clear metabolic improvement, represented
      by the significant fall of HbA1c. Therefore, though without ignoring the overall
      context of treatment and diabetes education, it is proposed that the relationship
      of the most practical features of insulin dosing to written norms of self-control
      should be emphasised.

PMID- 8257754
TI  - [Vaccination against hepatitis B in health workers and other staff in Barcelona].
AB  - OBJECTIVE: To analyse the results of a hepatitis B vaccination programme, in
      order to find the levels of acceptance of the programme and adherence to it, as
      well as the immunological response and the impact of age, gender and the index of
      corporal mass (ICM). DESIGN: This was a retrospective study. SETTING: Primary
      Care. PATIENTS AND OTHER PARTICIPANTS: 2,055 Primary Care professionals
      considered at risk (43.3% of the Area total). MEASUREMENTS AND MAIN RESULTS: Out
      of the total number of professionals at risk, 1,294 (63%) agreed to have the
      serological markers. The prevalence of markers of the hepatitis B virus (HBV) was
      16.07% (208), which increased with age (p < 0.0001). 87% had three doses
      (961/1,106). 863 (89.8%) of these went through the post-vaccination controls and
      levels of HB antibodies above 10 IU/ml were found in 790 (91.5%). The fourth dose
      produced favorable results (66.7%) in individuals with HB antibodies between 10
      and 100 IU/ml and unfavorable ones (3.8%) where the HB antibodies were below 10
      IU/ml. CONCLUSIONS: The hepatitis B vaccination programme has not enjoyed total
      acceptance by Primary Care professionals, although a satisfactory level of
      adherence has been reached. Age is the variable linked most closely to the risk
      of a poor immunological response, though ICM and gender should not be ignored.

PMID- 8257755
TI  - [An increase in alkaline phosphatases: an approach to the diagnosis of
      hyperthyroidism].

PMID- 8257756
TI  - [Diabetes: impact of the systematic use of the reflectometer in a rural
      population].

PMID- 8257757
TI  - [Sign of positive modesty].

PMID- 8257758
TI  - [Compliance with antihypertensive treatment].

PMID- 8257759
TI  - [The grieving process in a home for the aged].

PMID- 8257760
TI  - [Asthma: overlapping psychological and social factors].

PMID- 8257761
TI  - [How much does cerebral vasotherapy cost us?].

PMID- 8257762
TI  - [Lyell's syndrome: a problem to keep in mind in primary care].

PMID- 8257763
TI  - [Evaluation of the health care demand at a primary care center and its
      codification by the WONCA-CIPSAP-2 classification].

PMID- 8257764
TI  - Modular analysis of the control of complex metabolic pathways.
AB  - The understanding of the functioning of the intact cell would be simplified
      appreciably if it were possible first to analyze particular modules of cell
      physiology separately, and then to integrate the information so as to yield
      understanding of the control structure in terms of the mutual regulation of the
      modules. Here we develop a quantitative method based on Metabolic Control
      Analysis that makes this possible: The relevant properties of the modules are
      contained in "overall" elasticity coefficients, which reflect the changes in
      fluxes in the module upon a small variation of the environment of the module,
      allowing the latter to attain steady state. We show how overall control
      coefficients, which reflect the control exerted by the processes catalyzed by
      each module, can be expressed into the overall elasticity coefficients. We derive
      corresponding summation and connectivity theorems. A number of possible divisions
      of physiological systems into modules is discussed. This work is a generalization
      of previous analyses of overall control properties in that it allows for multiple
      fluxes to connect the modules, and reaction stoichiometries of any complexity.

PMID- 8257765
TI  - A new front-face optical cell for measuring weak fluorescent emissions with time
      resolution in the picosecond time scale.
AB  - Recent developments of ultrafast fluorimeters allow measuring time-resolved
      fluorescence on the picosecond time scale. This implies one is able to monitor
      lifetimes and anisotropy decays of highly quenched systems and of systems that
      contain fluorophores having lifetimes in the subnanosecond range; both systems
      that emit weak signals. The combination of weak signals and very short lifetimes
      makes the measurements prone to distortions which are negligible in standard
      fluorescence experiments. To cope with these difficulties, we have designed a new
      optical cell for front-face optics which offers to the excitation beam a
      horizontal free liquid surface in the absence of interactions with optical
      windows. The new cell has been tested with probes of known lifetimes and
      anisotropies. It proved very useful in detecting tryptophan fluorescence in
      hemoglobin. If only diluted samples are available, which cannot be used in front
      face optics, regular square geometry can still be utilized by inserting light
      absorbers into a cuvette of 1 cm path length.

PMID- 8257766
TI  - Intramolecular dynamics in the environment of the single tryptophan residue in
      staphylococcal nuclease.
AB  - The dipole relaxational dynamics in the environment of a single tryptophan
      residue Trp-140 in staphylococcal nuclease was studied by time-resolved (multi
      frequency phase-modulation) spectroscopy and selective red-edge excitation. The
      long-wavelength position of the fluorescence spectrum (at 343 nm) and the absence
      of red-edge excitation effects at 0 and 20 degrees C indicate that this residue
      is surrounded by very mobile protein groups which relax on the subnanosecond time
      scale. For these temperatures (0-20 degrees C) the steady-state emission spectra
      did not show the excitation-wavelength dependent shifts (red-edge effects) for
      excitation wavelengths from 295 to 308 nm; however, the anisotropy decay rate is
      slow (tens of nanoseconds). This suggests that the spectral relaxation is due to
      mobility of the surrounding groups rather than the motion of the tryptophan
      itself. The motions of the tryptophan surrounding are substantially retarded at
      reduced temperatures in viscous solvent (60% glycerol). The temperature
      dependence of the difference in position of fluorescence spectra at excitation
      wavelengths 295 and 305 nm demonstrate the existence of red-edge effect at sub
      zero temperatures, reaching a maximum value at -50 degrees C, where the steady
      state emission spectrum is shifted to 332 nm. The excitation and emission
      wavelength dependence of multi-frequency phase-modulation data at the half
      transition point (-40 degrees C) demonstrates the existence of the nanosecond
      dipolar relaxations. At -40 degrees C the time-dependent spectral shift is close
      to monoexponential with the relaxation time of 1.4 ns.

PMID- 8257768
TI  - A thermodynamic and spectroscopic study on the binding of berenil to poly d(AT)
      and to poly (dA) x poly (dT).
AB  - The complete thermodynamic profile for the non-intercalative binding of berenil
      to the alternating copolymer poly d(AT) and to the homopolymer poly (dA) x poly
      (dT) was investigated. Differential Scanning Calorimetry (DSC) and UV absorbance
      spectroscopy have been used to characterize and to compare the binding of berenil
      to the different synthetic polymers. Both double stranded DNA's show two types of
      binding; one stronger binding mode at low berenil concentrations and a weaker, in
      the case of poly d(AT)-berenil complexes slightly cooperative binding mode at
      higher drug to base pair ratios. For the interaction of berenil with poly d(AT)
      the thermodynamic data delta G(bind)0 = -33 kJ/mol drug, delta H(bind)0 = -29
      kJ/mol of drug and delta S(bind)0 = +13 J/Kmol of drug were calculated. For the
      minor groove binding of berenil to poly (dA) x poly (dT) the following values
      were obtained: delta G(bind)0 = -34 kJ/mol of drug, delta H(bind)0 = -25 kJ/mol
      of drug and delta S(bind)0 = +30 J/Kmol of drug. Temperature-dependent UV
      absorbance spectroscopy revealed for both duplexes a biphasic "melting" behavior.
      However, the saturated nucleic acids (drug to base pair ratio 0.33) "melted"
      monophasically and with a decreased length of the cooperative unit. The obtained
      apparent equilibrium constants K(app) for the complexation with the discharged
      drug molecule showed to be a sensitive function of the ionic environment. But in
      contradiction to the expected release of two counterions into the solvent only a
      value of 1.0 was observed for the alternating copolymer poly d(AT). The
      complexation of berenil with poly (dA) x poly (dT) is followed by a release of
      1.4 ions indicating stronger electrostatic interactions. For both polynucleotides
      the predicted release of two ions is not achieved. This is due to the presence of
      a binding mode, which involves less electrostatic interactions. From the complete
      data set it is proposed that the mode of binding is closely related to that found
      for the analogue minor groove binders DAPI and netropsin.

PMID- 8257767
TI  - Tryptophan fluorescence quenching in rabbit skeletal myosin rod.
AB  - The solvent accessibility of the four tryptophans of rabbit skeletal muscle
      myosin rod was investigated using steady-state and time-resolved fluorescence
      quenching by iodide, acrylamide, and cesium. The quenching by iodide and
      acrylamide was biphasic; the discrete, long lifetime component was quenched with
      bimolecular collision constants (kq) of 1 x 10(9) M-1 s-1 and 1.6 x 10(9) M-1 s
      1, respectively, while the Gaussian distributed, short lifetime component was
      quenched with a kq value of 0.3 x 10(9) M-1 s-1 and 0.04 x 10(9) M-1 s-1,
      respectively. Comparison with kq values for N-acetyl-tryptophanamide indicated
      that the fractional solvent accessibility was about 25% for the long and less
      than 10% for the short lifetime component. Cesium quenching was monophasic and
      provided evidence of an excess of positive charge around these tryptophans. Our
      findings cast doubt on the general application of the simple coiled-coil model to
      describe coiled-coil interactions in this protein in solution.

PMID- 8257769
TI  - Production methods for generating human monoclonal antibodies.

PMID- 8257770
TI  - An animal model to predict the immunogenicity of murine V regions in humans.
AB  - Clinical trials with genetically engineered chimeric mouse/human monoclonal
      antibodies have demonstrated that mouse variable regions differ dramatically in
      their degree of immunogenicity. These observations led us to search for an animal
      model that could predict mouse variable region (V region) immunogenicity prior to
      human clinical trials. We selected monoclonal antibodies 17-1A and B72.3 for
      study because human trials have demonstrated the very low immunogenicity of the
      mouse 17-1A V region and the high immunogenicity of the mouse B72.3 V region.
      Random-bred New Zealand white rabbits were injected intravenously with mouse 17
      1A, B72.3, or both using a dose and schedule comparable to human trials. After
      initial injection only two of ten rabbits developed an antibody response to mouse
      17-1A, while all five animals receiving a second injection developed antibody
      that was entirely mouse constant region-specific. On the other hand, nine of ten
      rabbits demonstrated an antibody response to initial infusion of mouse B72.3 that
      was greater than 90% specific for the complementarity-determining region
      components of the V regions. Competitive inhibition with isolated heavy and light
      chains demonstrated specificity for heavy or light chains (approximately 60%) or
      a requirement for both (40%). Thus, as in humans, the V region of 17-1A elicited
      little or no immune response in rabbits, while the V region of B72.3 was highly
      immunogenic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257771
TI  - Preparation of a human monoclonal antibody derived from cervical lymph nodes of a
      patient with anaplastic carcinoma of the thyroid.
AB  - An anaplastic carcinoma cell line, KOA-2, was established from a 59-year-old
      patient with anaplastic carcinoma of the thyroid who died only one month after
      diagnosis in association with rapid progress of her disease. A human monoclonal
      antibody, 3C5 (IgM), was generated by a fusion of human B lymphoblastoid cell
      line, HO-323, with lymphocytes from cervical lymph nodes of the patient, who had
      been treated with local immunotherapy. Immunocytostaining demonstrated that 3C5
      reacted with KOA-2, and membrane immunofluorescence demonstrated that 3C5 reacted
      with cell membranes. Immunohistochemical staining studies demonstrated selective
      reaction of 3C5 with three malignant tumors, anaplastic carcinoma of the thyroid
      (2/4 sampled tested), papillary carcinoma of the thyroid (8/12), and breast
      cancer (2/6), but no reaction with specimens of benign thyroid disease or normal
      thyroid gland was demonstrated. The monoclonal antibody and the cell line
      established from one patient have potential use in the analysis of carcinogenesis
      and applications to therapy of anaplastic carcinoma of the thyroid.

PMID- 8257772
TI  - Cancer-specific binding of a mouse MAb vs. Candida krusei cytochrome c: an
      antigen recognized by a cancer-associated human MAb HB4C5.
AB  - More than 60 mouse monoclonal antibodies directed to cytochrome c from Candida
      krusei with different specificities were raised. Most of these monoclonal
      antibodies, except for three of them, did not cross-react with bovine cytochrome
      c. By the immunoblotting method, the monoclonal antibodies of clones HCC 5-13, 9
      2, and 10-5 reacted with the Candida cytochrome c, which had been transferred
      onto nitrocellulose membrane, but those of clones HCC 1-22, 6-3, and 17-3 did
      not, although all these monoclonal antibodies strongly reacted with coated
      Candida cytochrome c on plastic immunoplates when examined by ELISA. On the
      contrary, monoclonal antibody activities of clones HCC 1-22, 6-3, and 17-3 in
      binding to the coated cytochrome c in ELISA were inhibited competitively by the
      addition of extra Candida cytochrome c, whereas those of clones HCC 5-13, 9-2,
      and 10-5 were not inhibited. Among these monoclonal antibodies, the antibody of
      clone HCC 6-3, which showed a good reactivity to added cytochrome c in inhibiting
      ELISA reaction but was not reactive with the transblotted cytochrome c on
      nitrocellulose, was found to be reactive with human lung cancer tissues
      specifically with no reactivity to normal tissues. The immunostaining of lung
      cancer tissue showed that this mouse monoclonal antibody to Candida cytochrome c
      reacted to the cytoplasmic fraction of the cancer cells specifically.

PMID- 8257773
TI  - Direct localization comparison of murine and chimeric B72.3 antibodies in
      patients with colon cancer.
AB  - To compare radiolocalization of murine B72.3 (m-B72.3) and mouse/human chimeric
      B72.3 (ch-B72.3) antibodies, five patients with biopsy confirmed adenocarcinoma
      of the colon received both radiolabeled antibodies 4 or 7 days before laparotomy.
      Following antibody administration, preoperative gamma camera images showed
      localization to sites of disease in four of the five patients. Autoradiography of
      resected specimens showed that both labeled antibodies localized specifically to
      the tumor with only minimal amounts in normal tissues. Radioactivity from each
      isotope in biopsy specimens of tumor and normal tissues was quantitated by
      scintillation gamma counting. Comparison of the percentages of injected
      activities for each antibody in resected tumor and normal tissue yields tumor to
      normal tissue radiolocalization ratios of 2.7-13.3 and 0.9-6.3 for murine and
      chimeric antibodies, respectively. The higher ratios for murine antibody were due
      to lower normal tissue levels, reflecting its faster clearance from the
      circulation, whereas the quantitative uptake of labeled antibody was always
      greater with the chimeric antibody. The chimera to murine antibody ratios in
      tumor of 1.1-2.7 suggest modest enhancement of tumor localization with chimeric
      antibody because of its longer half-life.

PMID- 8257774
TI  - Application of cellular ELISA (CELISA) to the detection of human monoclonal
      autoantibodies.
AB  - This work describes the application of cellular enzyme-linked immunosorbent assay
      (CELISA) for the detection of both polyreactive and monospecific human monoclonal
      antibodies against autoantigens. The CELISA is ideally suited for the screening
      of a large number of hybridoma culture supernatants, being, in this way, superior
      to other methods commonly used for the detection of autoantibody activity, such
      as indirect immunofluorescence on tissue sections and slide cell preparations, in
      terms of speed and sensitivity. This assay demonstrated higher sensitivity than
      ELISA using autoantigenic extracts from rabbit thymus, human spleen,
      nucleoprotamine, and salmon sperm nuclei, and enzyme immunoassays using ssDNA,
      dsDNA, and affinity purified autoantigens as substrate. The CELISA has been also
      successfully applied to the detection of autolymphocytotoxic antibody activity in
      heterohybridoma supernatants.

PMID- 8257775
TI  - Extracellular phospholipase A2 expression and inflammation: the relationship with
      associated disease states.
AB  - Human non-pancreatic PLA2 has been the object of intense scrutiny for a
      relatively short period of time. Its role in physiology remains enigmatic. While
      PLA2 may serve to remodel or remove peroxidised or senescent phospholipids, the
      enormous magnitude of its upregulation during infectious or inflammatory episodes
      is consistent with a role in host defense. However, the nature of this role
      remains elusive. Attempts to relegate this enzyme to the genre of acute phase
      reactants have not been helpful in unravelling its role. Difficulty in obtaining
      adequate amounts of native snp-PLA2 prior to the availability of recombinant snp
      PLA2 led to the widespread use of snake venom homologs, particularly in studies
      of the biology of PLA2. This review has underscored the pitfalls inherent in that
      approach given the major differences between some venom PLA2s as compared to snp
      PLA2. In addition, it bears reiterating that the complex composition of venom
      allows for potentiation of PLA2 activity by other constituents present in venom.
      Whether human host defense networks employ this interactive strategy is largely
      unknown. Nonetheless, in spite of these reservations, some very compelling data
      have emerged in recent years implicating snp-PLA2 in the initiation or
      potentiation of local and systemic inflammatory processes. These include sepsis
      and associated acute lung injury as well as inflammatory arthritides, with
      rheumatoid arthritis as the prototype. The mechanisms of snp-PLA2 homeostasis are
      considerably better understood, and it has become apparent that snp-PLA2 is an
      integral part of a larger network of proinflammatory cytokines, growth factors
      and lipid mediators. The interrelationship between the functions of secretory and
      cytosolic PLA2s remains to be defined. A number of selective PLA2 inhibitors have
      been identified which will allow for discrimination between the actions of these
      classes of PLA2. The availability of synthetic inhibitors in conjunction with
      endogenous modulators of PLA2s will shift the biology of PLA2 from the realm of
      the inferential to that of the mechanistic.

PMID- 8257776
TI  - Biochemical and pharmacological properties of SR 27388, a dual antioxidant and
      PAF receptor antagonist.
AB  - SR 27388 (N-(2-dimethylaminoethyl)-N-(3-pyridinylmethyl[4-(3,5-di(tert- butyl)-4
      hydroxylphenyl)thiazol-2-yl]amine) is a potent and competitive antagonist of the
      binding of [3H]PAF to its receptor on rabbit platelets exhibiting an equilibrium
      inhibition constant for PAF binding of 10.5 +/- 1.2 nM (n = 3). SR 27388 potently
      inhibited PAF-induced aggregation of rabbit platelets in vitro (IC50 = 65 +/- 12
      nM) (n = 4). In this respect, SR 27388 was as potent as the
      triazolothienodiazepine WEB-2086 against PAF-induced aggregation of rabbit
      platelets and had no effect on the action of other platelet aggregating agents.
      SR 27388 prevented in a dose-dependent manner the formation of thiobarbituric
      acid reactive substances during membrane peroxidation (IC50 = 0.7 microM) and
      inhibited reduction of the stable 1,1-diphenyl-2-picrylhydrazyl radical,
      indicating that the antioxidant potency of SR 27388 was due to an efficient
      radical scavenging activity. SR 27388 displayed marked in vitro inhibition of
      zymosan-induced oxidative burst in human monuclear cells (IC50 = 3 microM). In
      vivo, SR 27388 protected mice from 100 micrograms/kg PAF-induced death with an
      ED50 value of 500 micrograms/kg, when given i.v., 5 min before PAF challenge or
      p.o. (ED50 = 800 micrograms/kg) when given 1 h before PAF administration.
      Similarly, i.v. or oral doses of SR 27388 afforded in mice complete protection
      against endotoxin-induced lethality (ED50 values were 250 micrograms/kg and 1.3
      mg/kg, respectively). Neither BHT, vitamin E nor catechin exhibited significant
      protection against PAF- or endotoxin-induced death. In ovalbumin-presensitized
      rabbits, SR 27388 premixed with the allergen inhibited in a dose-dependent manner
      allergen-induced oedema formation in the skin (ED50 = 0.1 mumol/site). After an
      i.v. administration of 10 mg/kg, SR 27388 significantly protected mice against
      alloxan-induced diabetes. These results show that SR 27388 is a potent and orally
      active dual PAF receptor antagonist and antioxidant.

PMID- 8257777
TI  - Platelet activating factor interaction with tumor necrosis factor in myocardial
      ischaemia-reperfusion injury.
AB  - The role played by platelet-activating factor (PAF) and tumor necrosis factor
      (TNF-alpha) in myocardial ischaemia-reperfusion injury was investigated.
      Pentobarbital anaesthetized rats were subjected to left main coronary artery
      ligation (1 h) followed by reperfusion (1 h; MI/R). Sham-operated rats were used
      as controls (Sham MI/R). Myocardial ischaemia-reperfusion injury produced a
      marked myocardial injury (necrotic area/area-at-risk = 60 +/- 5%; necrotic
      area/total area = 50 +/- 6%), high serum creatine phosphokinase activity (Sham
      MI/R = 25 +/- 10 U/ml; MI/R = 190 +/- 12 U/ml), a severe leukopenia (Sham MI/R =
      10367 +/- 630 WBC x mm3; MI/R = 4123 +/- 120 WBC x mm3) and elevated myocardial
      myeloperoxidase activity (investigated as an index of leukocytes adhesion and
      accumulation) in the area-at-risk (6.2 +/- 0.5 U x 10(-3)/g tissue) and in
      necrotic area (6.6 +/- 0.7 U x 10(-3)/g tissue. Plasma PAF and serum TNF-alpha
      were significantly increased only during reperfusion. The peak of PAF plasma
      levels (6.5 +/- 1.2 pmol/ml) occurred earlier (15 min of reperfusion) than the
      peak of serum TNF-alpha (150 U/ml at 30 min of reperfusion). At the end of
      reperfusion, macrophage TNF-alpha was also enhanced (Sham MI/R = undetectable;
      MI/R = 148 +/- 12 U/ml). The administration of CV 6209, a specific PAF receptor
      antagonist (5 mg/kg, 5 min after occlusion), significantly reduced myocardial
      injury (necrotic area/area-at-risk = 27 +/- 3%, P < 0.001; necrotic area/total
      area = 10 +/- 2%, P < 0.001), blunted the increase in serum creatine
      phosphokinase (70 +/- 12 U/ml), partially restored leukopenia (8234 +/- 143 WBC x
      mm3) and lowered myeloperoxidase activity in area-at-risk (2.3 +/- 0.3 U x 10(
      3)/g tissue; P < 0.001) and in necrotic area (2.8 +/- 0.5 U x 10(-3)/g tissue).
      In addition, administration of CV 6209 reduced the serum and macrophage levels of
      TNF-alpha. The results of this study, therefore, suggest that PAF and TNF-alpha
      are key mediators of myocardial ischaemia-reperfusion injury and that PAF plays a
      permissive role in inducing the release of other factor(s) relevant to
      reperfusion injury.

PMID- 8257778
TI  - Adhesion molecules and inhibitors of glycosylation in cancer.
AB  - Expression of aberrant oligosaccharide moieties of glycoproteins and glycolipids
      is a typical characteristic of essentially all animal and human tumors,
      irrespective of the carcinogenic mechanism. Evidence is presented to document
      that transformation-associated alternations in the oligosaccharide moieties of
      surface and adhesive glycoproteins are responsible, at least in part, for
      expression of the malignant phenotype. However, the contribution of carbohydrates
      to tumor progression and metastasis cannot be fully assessed until more
      information is available concerning the multiple mechanisms that regulate cell
      adhesion and carbohydrate biosynthesis. Nevertheless, our rudimentary
      understanding of the carbohydrate-dependent events involved in cell adhesion and
      metastasis has resulted in animal studies to develop novel and exciting
      approaches to cancer therapy.

PMID- 8257779
TI  - Adhesion molecules in lymphoma metastasis.
AB  - Lymphoma cells are derived from normal lymphocytes and therefore their metastatic
      behavior is probably based on mechanisms of migration of these normal
      progenitors. Several adhesion molecules that are involved in this normal
      migration, have been identified. These include the 'lymph node homing receptors'
      and the leukocyte (beta 2) integrins. The limited evidence available for a role
      of these molecules in lymphoma metastasis is reviewed here. Recently, the
      regulation of the activity of adhesion molecules was shown to be of pivotal
      importance for the control of leukocyte traffic. The implications of these
      findings for lymphoma metastasis are discussed.

PMID- 8257780
TI  - Fibronectin and cancer: rationales for the use of antiadhesives in cancer
      treatment.
AB  - Alterations in the rate and pattern of cell movement are prominent features of
      many human diseases, including inflammation, cardiovascular disease and cancer.
      The ability to regulate the interactions of cells with each other and with
      adhesion factors in extracellular matrices therefore offers a novel approach to
      the treatment of these diseases. The intention of this article is to provide an
      overview of the role of the adhesive glycoprotein fibronectin and its receptors
      in the adhesive behavior of tumors, to review ongoing work that is aimed at
      developing agents with the ability to regulate adhesion to fibronectin, and to
      highlight aspects of the malignant phenotype that are potential targets for
      intervention with such agents.

PMID- 8257781
TI  - Differential expression of the 67 kDa laminin receptor in cancer.
AB  - During tumor invasion and metastasis, cancer cells interact with host tissues.
      Penetration of the extracellular matrix by cancer cells is mediated in part by
      interaction of cell surface receptors with laminin, the major glycoprotein
      component of the basement membrane. A variety of cell surface laminin binding
      proteins have been identified, including members of both the integrin and non
      integrin families. The 67 kDa laminin receptor is a non-integrin protein with a
      high affinity for laminin. Immunohistochemical, immunoblot, RNA blot and in situ
      hybridization studies have demonstrated that levels of 67 kDa laminin receptor
      protein and/or mRNA are increased in a variety of human adenocarcinomas. In
      contrast, cancers of squamous cell origin may not demonstrate the same pattern of
      laminin receptor expression.

PMID- 8257782
TI  - The molecular basis for the cytoadherence of Plasmodium falciparum-infected
      erythrocytes to endothelium.
AB  - Human erythrocytes infected with the human malaria parasite Plasmodium
      falciparum, bind to post-capillary venular endothelium and to uninfected red
      blood cells via specific receptor-ligand interactions. The interactions between
      malaria-parasitized erythrocytes and host cells is a highly cooperative and
      finely regulated process which contributes both to the evasion of host immune
      mechanisms and to the pathogenesis of the disease, in particular the development
      of cerebral malaria. The cellular and molecular interactions responsible for the
      adhesion of parasitized red cells to host cells are the subject of this review.

PMID- 8257783
TI  - Leishmania-macrophage interactions: multiple receptors, multiple ligands and
      diverse cellular responses.
AB  - Although a great deal of progress has been made over the last several years in
      understanding the interactions of leishmania with mammalian cells, much work
      remains. The consensus from many of these studies is that promastigotes utilize
      multiple receptors to bind to macrophages. Ongoing studies involving the use of
      both purified and molecularly cloned receptors and ligands should eventually
      provide a more detailed understanding of the mechanisms by which promastigotes
      infect macrophages. At this time, the mechanism(s) involved in the interaction of
      amastigotes with mammalian cells remains somewhat enigmatic. Since amastigotes
      are responsible for the cell to cell spread of leishmania, gaining a better
      understanding of amastigote-macrophage interactions represents an important goal
      of future leishmania research.

PMID- 8257784
TI  - Trypanosoma cruzi: mechanisms for entry into host cells.
AB  - Infective trypomastigote stages of the obligate intracellular protozoan parasite
      Trypanosoma cruzi are capable of entering virtually any mammalian cell in vitro.
      Entry is a complex process, involving initial parasite attachment to surface
      moieties of the target cell, internalization of the parasite via formation of a
      vacuole, and finally disruption of the vacuolar membrane to permit access of the
      parasite to the host cell cytoplasm. Attachment requires parasite metabolic
      energy. At sites of parasite entry recruitment of host cell lysosomes may occur,
      and lysosomal membrane components contribute prominently to formation of the
      parasitophorous vacuole. Parasite escape from the vacuole depends upon vacuolar
      acidification and is mediated by the coordinated action of a parasite-derived
      neuraminidase/trans-sialidase that is capable of desialylating host-derived
      vacuolar membrane constituents, and a parasite-derived trans-membrane pore
      forming protein. Dissection of the entry process at both the organellar and
      molecular level is providing fundamental and complementary insights into
      microbial pathogenesis and cell biology.

PMID- 8257785
TI  - Interactions between Toxoplasma gondii and its mammalian host cells.
AB  - Toxoplasma is a protozoan parasite that is uniquely adapted for invading and
      surviving within a wide range of host cells. The parasite actively invades the
      cell, forming a novel vacuole that originates from the host cell plasma membrane.
      The vacuole membrane is rapidly modified to remove host cell proteins and this
      compartment subsequently resists fusion with all other host cell endocytic
      compartments. Shortly after invasion, the parasite secretes a variety of proteins
      by a process of regulation exocytosis and elaborates an extensive array of
      membranous tubules that form a network connecting with the vacuolar membrane.
      Understanding the formation and modification of this unique vacuole may reveal
      novel mechanisms for subverting host cell endocytic pathways that lead to
      intracellular survival.

PMID- 8257786
TI  - Export of parasite proteins to the erythrocyte in Plasmodium falciparum-infected
      cells.
AB  - The human malaria parasite Plasmodium falciparum invades erythrocytes and
      develops within a parasitophorous vacuole. It has been proposed that constitutive
      protein export from the intracellular parasite is mediated by two types of
      secretory vesicles. One is targeted to the parasite plasma membrane and the other
      to a domain where the plasma and vacuolar membranes of the parasite are fused
      into a single bilayer. This differential targeting of vesicles may be regulated
      by the developmental stage of the parasite. Regulated secretion through the
      apical organelles at or immediately after the invasion of a new red cell may
      allow protein insertion at the erythrocyte surface and mediate formation of the
      joint membrane domain of constitutive secretion.

PMID- 8257787
TI  - Hemoglobin degradation in Plasmodium-infected red blood cells.
AB  - Intraerythrocytic malaria parasites (Plasmodia) degrade enormous amounts of
      hemoglobin during a short period of their life cycle. The process involves
      ingestion of red blood cell cytoplasm through the cytostome, delivery to acidic
      digestive vacuoles and sequential, efficient proteolysis by a set of specific
      hydrolases. Amino acids are generated for the growth and maturation of the
      organism; the heme byproduct is sequestered into a crystalline lattice called
      hemozoin. These specialized functions makes the digestive vacuole a prime target
      for antimalarial chemotherapy.

PMID- 8257788
TI  - The molecular basis of transformation of lymphocytes by Theileria parva
      infection.
AB  - The protozoan intracellular parasites, Theileria parva and Theileria annulata,
      infect cattle and cause severe and fatal leukocytic proliferative diseases. The
      proliferation is dependent on the presence of the parasites in the host cell
      cytoplasm. T. parva-infected cells proliferate permanently in cell culture and
      exhibit many features characteristic of tumor cells. The proliferation is
      reversible by treatment with parasite-specific drugs. Constitutive expression of
      interleukin-2, its receptor and their transcription factor, NF-kappa B, are
      dependent on the parasite and suggest autocrine growth. Cell-cell contact
      possibly via T cell adhesion molecules has been shown to stimulate proliferation.

PMID- 8257789
TI  - Effects of intestinal insulin-like peptide on glucose catabolism in mealworm
      larval fat body in vitro: dependence on extracellular Ca2+ for its stimulatory
      action.
AB  - In vitro hormonally induced variations of glucose catabolism in mealworm fat body
      tissue were examined by a microradiorespirometric method. An insulin-like peptide
      (ILP) extracted from the midgut of last larval instar mealworm larvae
      significantly modified glucose catabolism and was dependent on energy metabolism
      and on the Ca2+ concentration in the culture medium. Using two different labelled
      substrate molecules, the stimulatory effects of ILP (compared with those of
      mammalian insulin) on the relative use of the pentose cycle as opposed to the
      glycolytic-citric acid cycle by the mealworm fat body were measured in vitro.
      Metabolic variations were evaluated using either [1-14C]glucose or [6-14C]glucose
      as substrates. Time course and dose-response curves of ILP and the hormonally
      induced variations in total CO2 and 14CO2 kinetics were determined. Modification
      in the specific radioactivity kinetics of 14CO2 derived from [1-14C] glucose and
      [6-14C]glucose molecules under hormonal effects were observed. As demonstrated in
      in vivo studies, ILP stimulated the relative utilization of the pentose cycle.
      However, this effect was observed much more rapidly, but for a shorter time, with
      fat body in vitro. Mammalian insulin produced similar, but not identical effects.
      Variations in transmembranous Ca2+ cellular exchanges, induced by either EGTA,
      nifedipine, or calcium ionophore ionomycin included in the culture medium,
      indicated that the stimulatory effects of ILP depends on this cation.

PMID- 8257790
TI  - Expression of a parasitism-specific protein in lepidopteran hosts of Chelonus sp.
AB  - The hemolymph of each noctuid species successfully parasitized by Chelonus near
      curvimaculatus possessed a parasitism-specific protein (PSP) previously
      identified in host T. ni (Insect Biochem. 19:445;21:845). Expression of PSP
      occurred in a stage-specific manner in the stadium during which the host
      undergoes precocious metamorphosis. The appearance of the protein was not due to
      nutritional stress associated with parasitism of hosts, since starved
      nonparasitized larvae did not produce the protein, or to low juvenile hormone
      titers occurring in precociously metamorphosing hosts, but rather was dependent
      on the presence of the endoparasite larva. Results of an in vivo incorporation
      experiments with [35S]-methionine showed that synthesis and subsequent appearance
      of the protein in the hemolymph of parasitized hosts was abrogated by prior
      surgical removal of endoparasite. Immunoprecipitation analysis of proteins from
      C. near curvimaculatus larvae cultured in vitro using antibodies specific to PSP
      indicated that the source of the protein was the endoparasite. Synthesis of PSP
      by the endoparasitic larvae with its subsequent secretion into the hemocoel of
      hosts was specific to the advanced stages of parasite development prior to its
      regression from the host.

PMID- 8257791
TI  - The beta 4 subunit cytoplasmic domain mediates the interaction of alpha 6 beta 4
      integrin with the cytoskeleton of hemidesmosomes.
AB  - The alpha 6 beta 4 integrin is structurally distinct from all the other known
      integrins because the cytoplasmic domain of beta 4 is unusually large and
      contains four type III fibronectin-like modules toward its C-terminus. To examine
      the function of the beta 4 cytoplasmic tail, we have expressed full-length and
      truncated human beta 4 cDNAs in rat bladder epithelial 804G cells, which form
      hemidesmosome-like adhesions in vitro. The cDNA encoded wild-type beta 4 subunit
      associated with endogenous alpha 6 and was recruited at the cell surface within
      hemidesmosome-like adhesions. A recombinant form of beta 4, lacking almost the
      entire cytoplasmic domain associated with alpha 6, reached the cell surface but
      remained diffusely distributed. A beta 4 molecule lacking almost the entire
      extracellular portion did not associate with alpha 6 but was correctly targeted
      to the hemidesmosome-like adhesions. Thus, the cytoplasmic portion of beta 4
      contains sequences that are required and may be sufficient for the assembly of
      the alpha 6 beta 4 integrin into hemidesmosomes. To localize these sequences we
      examined the properties of additional mutant forms of beta 4. A truncated beta 4
      subunit, lacking the most C-terminal pair of type III fibronectin homology
      domains, was incorporated into hemidesmosome-like adhesions, but another
      recombinant beta 4 molecule, lacking both pairs of type III fibronectin repeats,
      was not. Finally a recombinant beta 4 molecule, which was created by adjoining
      the region of the cytoplasmic domain including all type III repeats to the
      transmembrane segment, was efficiently recruited in hemidesmosome-like adhesions.
      Taken together these results suggest that the assembly of the alpha 6 beta 4
      integrin into hemidesmosomes is mediated by a 303-amino acid region of beta 4
      tail that comprises the first pair of type III fibronectin repeats and the
      segment between the second and third repeats. These data imply a function of a
      specific segment of the beta 4 cytoplasmic domain in interaction with
      cytoskeletal components of hemidesmosomes.

PMID- 8257792
TI  - Delays in anaphase initiation occur in individual nuclei of the syncytial
      Drosophila embryo.
AB  - The syncytial divisions of the Drosophila melanogaster embryo lack some of the
      well established cell-cycle checkpoints. It has been suggested that without these
      checkpoints the divisions would display a reduced fidelity. To test this idea, we
      examined division error frequencies in individuals bearing an abnormally long and
      rearranged second chromosome, designated C(2)EN. Relative to a normal chromosome,
      this chromosome imposes additional structural demands on the mitotic apparatus in
      both the early syncytial embryonic divisions and the later somatic divisions. We
      demonstrate that the C(2)EN chromosome does not increase the error frequency of
      the late larva neuroblast divisions. However, in the syncytial embryonic nuclear
      divisions, the C(2)EN chromosome produces a 10-fold increase in division errors
      relative to embryos with a normal karyotype. During late anaphase of the
      neuroblast divisions, the sister C(2)EN chromosomes cleanly separate from one
      another. In contrast, during late anaphase of the syncytial divisions in C(2)EN
      bearing nuclei, large amounts of chromatin often lag on the metaphase plate. Live
      analysis of C(2)EN-bearing embryos demonstrates that individual nuclei in the
      syncytial population of dividing nuclei often delay in their initiation of
      anaphase. These delays frequently lead to division errors. Eventually the
      products of the nuclei delayed in anaphase sink inward and are removed from the
      dividing population of syncytial nuclei. These results suggest that the
      Drosophila embryo may be equipped with mechanisms that monitor the fidelity of
      the syncytial nuclear divisions. Unlike checkpoints that rely on cell cycle
      delays to identify and correct division errors, these embryonic mechanisms rely
      on cell cycle delays to identify and discard the products of division errors.

PMID- 8257793
TI  - The alpha and beta subunits of nematode actin capping protein function in yeast.
AB  - We cloned and analyzed two genes, cap-1 and cap-2, which encode the alpha and
      beta subunits of Caenorhabditis elegans capping protein (CP). The nematode CP
      subunits are 55% (cap-1) and 66% (cap-2) identical to the chicken CP subunits and
      32% (cap-1) and 48% (cap-2) identical to the yeast CP subunits. Purified nematode
      CP made by expression of both subunits in yeast is functionally similar to
      chicken skeletal muscle CP in two different actin polymerization assays. The
      abnormal cell morphology and disorganized actin cytoskeleton of yeast CP null
      mutants are restored to wild-type by expression of the nematode CP subunits.
      Expression of the nematode CP alpha or beta subunit is sufficient to restore
      viability to yeast cap1 sac6 or cap2 sac6 double mutants, respectively.
      Therefore, despite evolution of the nematode actin cytoskeleton to a state far
      more complex than that of yeast, one important component can function in both
      organisms.

PMID- 8257794
TI  - Suppression of a sec63 mutation identifies a novel component of the yeast
      endoplasmic reticulum translocation apparatus.
AB  - Mutations in the SEC63 gene are associated with defects in protein translocation
      into the endoplasmic reticulum (ER) as well as in nuclear protein localization in
      Saccharomyces cerevisiae. To identify proteins that might interact and/or
      function with SEC63p, we cloned a high copy suppressor (HSS1) of the temperature
      sensitive lethal phenotype of the sec63-101 mutant. HSS1 is an allele-specific
      sec63 suppressor that encodes an integral ER membrane glycoprotein of 206 amino
      acids with the N-terminus in the ER lumen and C-terminal region in the cytoplasm.
      Haploid strains disrupted for HSS1 are temperature-sensitive for growth and
      accumulate precursor forms of Kar2p and invertase. The HSS1 null allele is
      synthetically lethal in combination with mutations affecting ER translocation. We
      propose that HSS1p is important for ER translocation and interacts with
      previously identified components of the yeast translocation apparatus. HSS1 is
      identical to SEC66, which encodes a glycoprotein complexed with SEC62p and
      SEC63p.

PMID- 8257795
TI  - Structural and functional characterization of Sec66p, a new subunit of the
      polypeptide translocation apparatus in the yeast endoplasmic reticulum.
AB  - SEC66 encodes the 31.5-kDa glycoprotein of the Sec63p complex, an integral
      endoplasmic reticulum membrane protein complex required for translocation of
      presecretory proteins in Saccharomyces cerevisiae. DNA sequence analysis of SEC66
      predicts a 23-kDa protein with no obvious NH2-terminal signal sequence but with
      one domain of sufficient length and hydrophobicity to span a lipid bilayer.
      Antibodies directed against a recombinant form of Sec66p were used to confirm the
      membrane location of Sec66p and that Sec66p is a glycoprotein of 31.5 kDa. A null
      mutation in SEC66 renders yeast cells temperature sensitive for growth. sec66
      cells accumulate some secretory precursors at a permissive temperature and a
      variety of precursors at the restrictive temperature. sec66 cells show defects in
      Sec63p complex formation. Because sec66 cells affect the translocation of some,
      but not all secretory precursor polypeptides, the role of Sec66p may be to
      interact with the signal peptide of presecretory proteins.

PMID- 8257796
TI  - The Caenorhabditis elegans homologue of the extracellular calcium binding protein
      SPARC/osteonectin affects nematode body morphology and mobility.
AB  - The extracellular matrix-associated protein, SPARC (osteonectin [Secreted Protein
      Acidic and Rich in Cysteine]), modulates cell adhesion and induces a change in
      cell morphology. SPARC expression in mammals is developmentally regulated and is
      highest at sites of extracellular matrix assembly and remodeling such as parietal
      endoderm and bone. We have isolated cDNA and genomic DNA clones encoding the
      Caenorhabditis elegans homologue of SPARC. The gene organization is highly
      conserved, and the proteins encoded by mouse, human, and nematode genes are about
      38% identical. SPARC consists of four domains (I-IV) based on predicted secondary
      structure. Using bacterial fusion proteins containing nematode domain I or the
      domain IV EF-hand motif, we show that, like the mammalian proteins, both domains
      bind calcium. In transgenic nematodes expressing a SPARC-lacZ fusion gene, beta
      galactosidase staining accumulated in a striated pattern in the more heavily
      stained muscle cells along the body. Comparison of the pattern of transgene
      expression to unc-54-lacZ animals demonstrated that SPARC is expressed by body
      wall and sex muscle cells. Appropriate levels of SPARC are essential for normal
      C. elegans development and muscle function. Transgenic nematodes overexpressing
      the wild-type SPARC gene were abnormal. Embryos were deformed, and adult
      hermaphrodites had vulval protrusions and an uncoordinated (Unc) phenotype with
      reduced mobility and paralysis.

PMID- 8257797
TI  - The extracellular matrix as a cell survival factor.
AB  - Programmed cell death (PCD) or apoptosis is a naturally occurring cell suicide
      pathway induced in a variety of cell types. In many cases, PCD is induced by the
      withdrawal of specific hormones or growth factors that function as survival
      factors. In this study, we have investigated the potential role of the
      extracellular matrix (ECM) as a cell survival factor. Our results indicate that
      in the absence of any ECM interactions, human endothelial cells rapidly undergo
      PCD, as determined by cell morphology, nuclei fragmentation, DNA degradation,
      protein cross-linking, and the expression of the PCD-specific gene TRPM-2. PCD
      was blocked by plating cells on an immobilized integrin beta 1 antibody but not
      by antibodies to either the class I histocompatibility antigen (HLA) or vascular
      cell adhesion molecule-1 (VCAM-1), suggesting that integrin-mediated signals were
      required for maintaining cell viability. Treatment of the cells in suspension
      with the tyrosine phosphatase inhibitor sodium orthovanadate also blocked PCD.
      When other cell types were examined, some, but not all, underwent rapid cell
      death when deprived of adhesion to the ECM. These results suggest that in
      addition to regulating cell growth and differentiation, the ECM also functions as
      a survival factor for many cell types.

PMID- 8257798
TI  - Heterokaryon myotubes with normal mouse and Duchenne nuclei exhibit sarcolemmal
      dystrophin staining and efficient intracellular free calcium control.
AB  - Duchenne and mdx muscle tissues lack dystrophin where it normally interacts with
      glycoproteins in the sarcolemma. Intracellular free calcium ([Ca2+]i) is elevated
      in Duchenne and mdx myotubes and is correlated with abnormally active calcium
      specific leak channels in dystrophic myotubes. We fused Duchenne human and normal
      mouse myoblasts and identified heterokaryon myotubes by Hoechst 33342 staining to
      measure the degree to which dystrophin introduced by normal nuclei could
      incorporate throughout the myotube at the sarcolemma and restore normal calcium
      homeostasis. Dystrophin expression in myotubes was determined by
      immunofluorescence and confocal laser scanning microscopy. Dystrophin was
      expressed at the sarcolemma in normal mouse and heterokaryon myotubes, but not in
      Duchenne myotubes. In heterokaryons, extensive dystrophin localization occurred
      at the sarcolemma even where only Duchenne nuclei were present, indicating that
      dystrophin does not exhibit nuclear domains. Heterokaryon, normal mouse and
      Duchenne myotube [Ca2+]i was measured using fura-2 and fluorescence ratio
      imaging. Heterokaryon and normal mouse myotubes were found to maintain similar
      levels of [Ca2+]i. In contrast, Duchenne myotubes had significantly higher
      [Ca2+]i (p < 0.001). Furthermore, the ability of heterokaryons to maintain normal
      [Ca2+]i did not depend on greater numbers of normal nuclei than Duchenne being
      present in the myotube. These results support the view that dystrophin expression
      in heterokaryons allows for efficient control of [Ca2+]i.

PMID- 8257799
TI  - Truncated analogues of endothelin and sarafotoxin are selective for the ETB
      receptor subtype.
AB  - The sarafotoxins (SRTXs) are a family of 21-amino acid bicyclic peptides that are
      structurally similar to the potent vasoconstrictors, the endothelins (ETs). SRTX
      6c exhibits high selectivity for the ETB receptor subtype over the ETA subtype.
      This selectivity may be a result of a modification at positions 9 or 13, which
      are Glu9 and Asn13 in SRTX-6c and Lys9 and Tyr13 in ET-1. The truncated linear
      endothelin [Ala11,15]ET-18-21 was also on ETB receptor-selective ligand with 6-nM
      binding affinity. Therefore, a series of truncated endothelin/sarafotoxin (8-21)
      hybrid analogues were prepared, varying the amino acid at residues 9 and/or 13.
      These peptides were assayed for binding in tissues selectively expressing either
      the ETA or the ETB receptor subtypes. All linear analogues showed poor ETA
      binding, while ETB affinity was sequence dependent. Monocyclic 11-15 disulfide
      containing analogues failed to bind to either ETA or ETB receptors at
      concentrations of up to 10 microM.

PMID- 8257800
TI  - Identification of cysteine-containing peptides during the peptide mapping of
      recombinant proteins.
AB  - Confirmation of a protein's cysteine content and of its location within the amino
      acid sequence is crucial in investigating the structural integrity of recombinant
      proteins. A combination of thiol-specific chemistry and peptide mapping by
      reversed-phase microbore HPLC was used to confirm the presence and map the
      location of cysteine residues in the primary sequences of recombinant porcine
      growth hormone and human tumor necrosis factor alpha. Recombinant proteins were
      conjugated with a hydrophobic iodoacetamide derivative, dimethylaminoazo-benzene
      iodoacetamide, and digested with trypsin. The peptide fragments were separated on
      a C8 microbore reversed-phase column using a linear acetonitrile gradient. The
      peptides containing the cysteine residues were selectively identified by
      monitoring with a diode-array detector at 215 nm with the reference wavelength
      set at 450 nm. Cysteine-containing peptides could be readily distinguished as
      inverted "negative" peaks relative to the baseline and noncysteine-containing
      peptides. Isolated peptide fragments were then sequenced in order to confirm the
      location of the cysteines in the proteins. This approach offers the benefits of
      selectively and rapidly identifying, from a single chromatrophic step, the
      cysteine-containing peptides of proteins. Furthermore, the use of the labeling
      reagent renders the cysteine-containing peptides more hydrophobic, thereby making
      them easier to separate from noncysteine-containing peptides.

PMID- 8257801
TI  - Rapid, high-resolution HPLC separation of peptides using small particles at
      elevated temperatures.
AB  - Practical advantages are described for operating small-particle columns at
      elevated temperatures to increase the peak capacity, resolution or speed for
      separating peptides. Columns of small, highly-purified porous silica microspheres
      with a dense covalently bonded, bulky alkylsilane stationary phase permit
      continuous operation at temperatures of at least 90 degrees C. Operation at
      elevated temperatures decreases mobile phase viscosity and enhances solute
      diffusion, resulting in increased column plate number and separation resolution.
      Higher temperatures also decrease column back pressure, permitting longer columns
      of small particles for separating complex mixtures requiring large plate numbers.
      Use of a sterically protecting di-isobutyl-n-octadecylsilane stationary phase
      ensures stable and reproducible columns for operation at high temperatures, with
      the aggressive low pH mobile phase preferred for separating peptides. The
      monomeric nature of this phase ensures rapid mass transfer and high column
      efficiency.

PMID- 8257802
TI  - Predictions from the regularities of the primary structure of proteins.
AB  - Statistical analysis of large data sets indicates the existence of short-range
      regularities in the primary structure of proteins. In this paper the range and
      measure of these short-range regularities and various prediction methods based on
      them are discussed. The methods include predictions for domain boundaries of
      multidomain proteins; sizes of low-energy building blocks used in the calculation
      of protein structure as an assembly of stable overlapping segments;
      replaceability of amino acids; cis and trans conformation of proline residues;
      disulfide-forming Cys residues; surface exposure of amino acids; and tyrosine
      sulfation sites in proteins.

PMID- 8257803
TI  - Branched polypeptides as antigens for influenza virus hemagglutinin and T-cell
      receptor subunits.
AB  - The multiple antigenic peptide (MAP) method was applied to improve the
      immunogenicity of synthetic peptides representing distinct regions of the
      influenza virus hemagglutinin (HA). A tetrameric MAP with multiply incorporated
      overlapping B- and T-cell epitopes was combined with a particular HA sequence
      representing the slightly modified fusion peptide on the C-terminus of the Lys
      core (MAP-1). As a result of repeated injections of BALB/c mice with MAP-1 but
      not with the monomeric HA1C[Arg] peptide, the appearance of MAP-1-specific
      antibodies crossreactive with the acid-pretreated virus could be observed. In
      vitro studies revealed the potency of the MAP-1 structure to induce proliferation
      of HA1C[Arg]-primed T-cells, and in vivo studies demonstrated the protective
      feature of the immune response elicited by MAP-1 and to a lesser extent by the
      monomeric HA1C[Arg]. The increased level of MAP-1 specific antibodies upon viral
      challenge shows the activation of MAP-1-specific B- and/or T-cells. The advantage
      of the previously verified FP3 helper T-cell epitope included in MAP-1 was
      further utilized to synthesize chimeric structures comprising short fragments of
      the zeta of (MAP-2) or delta (MAP-3) subunits of the T-cell antigen receptor
      (TCR) complex. The selected peptides of the zeta and delta-chain regions failed
      to elicit an antibody response in BALB/c mice as tetra- or octamers, but the
      inclusion of the modified fusion region resulted in an immunogenic
      construction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257804
TI  - Chromosome aberrations induced by Eumaitenine, a sesquiterpene isolated from
      Maytenus boaria Mol. in cultured CHO cells.

PMID- 8257805
TI  - Effect of thiola on acetaminophen induced hepatic necrosis in mice.

PMID- 8257806
TI  - Relationship between termiticide treatment and human pollution by chlordane,
      oxychlordane, and nonachlor.

PMID- 8257807
TI  - Markers of occupational exposure to pentachlorophenol.

PMID- 8257808
TI  - Hexachlorobenzene (HCB) in human milk in Spain from 1984 to 1991.

PMID- 8257809
TI  - Organochlorine residues in human milk in Spain. Polychlorinated biphenyls (PCBs)
      from 1988 to 1991.

PMID- 8257810
TI  - Cadmium contamination of deer livers in Connecticut.

PMID- 8257811
TI  - Evaluation of immunoassay tests in screening soil contaminated with
      polychlorinated biphenyls.

PMID- 8257812
TI  - Levels of Cd, Pb, and Ni in different types of vinegars.

PMID- 8257813
TI  - Copper contamination of sandy soils and effects on young Hamlin orange trees.

PMID- 8257814
TI  - Distribution of polycyclic aromatic hydrocarbons (PAHs) in three northern New
      Jersey waterways.

PMID- 8257815
TI  - Effects of sediment organic carbon on distribution of radiolabeled fluoranthene
      and PCBs among sediment, interstitial water, and biota.

PMID- 8257816
TI  - Degradational behavior of the pesticides glyphosate and diflubenzuron in water.

PMID- 8257817
TI  - Toxicity of verrucarin A to gametes and embryos of the purple sea urchin (Arbacia
      punctulata).

PMID- 8257818
TI  - Histopathological changes induced by malathion in the liver of a freshwater
      catfish, Heteropneustes fossilis (Bloch).

PMID- 8257819
TI  - Pharmacokinetic model for the disposition of 3-methylcholanthrene in channel
      catfish after slow intraaortic infusion.

PMID- 8257820
TI  - Predictive ability of the Daphnia magna IQ Toxicity Test for ten diverse water
      treatment additives.

PMID- 8257821
TI  - Uptake and translocation of Cd109 by two aquatic ferns in relation to relative
      toxic response.

PMID- 8257822
TI  - Effect of lethal and sublethal concentrations of cadmium on energetics in the
      gills of fry and fingerlings of Cyprinus carpio.

PMID- 8257824
TI  - Definition and functions of natural killer cells.

PMID- 8257823
TI  - Influence of production, processing, and storage conditions of resting eggs of
      Streptocephalus proboscideus (Crustacea: Branchiopoda: Anostraca) on the
      sensitivity of larvae to selected reference toxicants.

PMID- 8257825
TI  - Production and differentiation of NK linkage cells in bone marrow.
AB  - The production of natural killer (NK) cells from their bone marrow progenitors is
      a multistep developmental process requiring interaction of hemopoietic NK lineage
      cells, stromal cells and growth factors. In this review, recent studies on the
      generation of NK cells provide the basis for a model of NK cell production. The
      development of NK cells is suggested to be similar to that of B cells, the other
      major lymphocyte population produced in the bone marrow. This scheme, for which
      substantial data already exist and which is testable vis-a-vis other points, can
      be summarized as follows: large, proliferating progenitor NK cells (pro-NK) give
      rise, under the influence of stromal cells and/or growth factors to less rapidly
      proliferating NK precursor cells (pre-NK) which exhibit some but not all of the
      phenotypic and morphologic characteristics of NK cells. Pre-NK cells divided and
      differentiate into phenotypically recognizable primary NK cells in the bone
      marrow. Primary NK cells are not in cell cycle, have low but measurable lytic
      activity, and express the phenotype of resting NK cells. They exit the bone
      marrow to populate peripheral sites where they undergo further maturation, become
      activated by such agents as interferon and may undergo a new cycle of
      proliferation in response to viral infections or other stimuli.

PMID- 8257826
TI  - Natural killer cell subsets: maturation, differentiation and regulation.
AB  - Studies of the maturation and differentiation of human peripheral blood-derived
      natural killer (NK) cells were examined on isolated three subsets of NK cells.
      These subsets were separated based on their ability to bind and/or kill the
      target cells. Flow cytometry and cell-sorting analyses enabled the separation of
      free, binder and killer cells. These three subsets were subjected to various
      phenotypic and functional analyses. The findings suggest that the three subsets
      belong to the same lineage of maturation and differentiation, e.g. free and
      binders can mature into killer cells. The killer cells are not terminally
      differentiated as they respond to IL-2 and targets and proliferate. The response
      of free cells to IL-2 and IFN-alpha proceeds by distinct pathways, namely IL-2
      mediated activation and proliferation is under the control of endogenous TNF
      alpha production but not IFN-alpha-mediated activation. Regulation of several
      surface markers' expression is associated with functional maturation. In addition
      to activation, the cells can also undergo inactivation or anergy following
      interaction with targets. The binder and killer cells are the predominant subsets
      that become inactivated for cytotoxicity and their response to IL-2 is inhibited.
      The studies also show that various events associated with activation of
      cytotoxicity are under different regulatory controls than those for proliferation
      and secretion. These studies suggest that biochemical and molecular events
      associated with signalling and differentiation are now possible to unravel using
      the NK subsets.

PMID- 8257827
TI  - Human natural killer cell development from bone marrow progenitors: analysis of
      phenotype, cytotoxicity and growth.
AB  - We have developed a culture system allowing for generation of NK cells from human
      CD34+ bone marrow progenitors. The appearance of NK cells expressing CD56+, CD3-
      phenotype and large granular lymphocyte morphology was observed after 2-3 weeks
      of culture with IL-2. The NK cell appearance coincided with development of lytic
      activity. NK cells generated in bone marrow cultures proliferated actively
      (expansion index ranged from 2- to 200-fold). The phenotype of NK cells generated
      from CD34+ bone marrow deviated from peripheral blood NK cells in that a lower
      percentage of the former cells expressed CD16, CD2, CD7, and CD8 antigens. NK
      cells were also generated from CD34+ populations depleted of the CD34+, CD33+
      subset indicating that myeloid-committed progenitors are not required for NK cell
      development. The dose of IL-2 was not important for generation of NK cells;
      however, only high doses of IL-2 supported development of optimal NK cell
      cytotoxic potential. Addition of TNF-alpha facilitated IL-2-dependent NK cell
      generation. These data showed that NK cells can develop from early bone marrow
      progenitors and that this system may be instrumental in studies on NK cell
      lineage and differentiation.

PMID- 8257828
TI  - Receptors for the Fc fragment of IgG on natural killer cells.
AB  - Natural killer (NK) cells are capable of binding to immune-complexed IgG via CD16
      Fc gamma RIIIA molecules on their surface. This interaction activates the NK cell
      lytic mechanism and induces production of lymphokines by the activated cells. The
      exact molecular basis for CD16-mediated NK cell activation remains unclear;
      however, a number of recent studies have provided a framework for future
      research. It has been shown that CD16 perturbation on NK cells evokes a variety
      of early signal transduction events in these cells, such as
      polyphosphatidylinositol hydrolysis, [Ca2+]i increases and protein tyrosine
      kinase activation. Furthermore, the identification, of CD3-zeta/eta and/or Fc
      epsilon RI-gamma polypeptides complexed with CD16 in NK cells suggests a signal
      transduction mechanism analogous to those studied for the T cell receptor and Fc
      epsilon-receptor complexes. Therefore, research on each of these receptor
      complexes should now be viewed in light of a potential common signal transduction
      mechanism. Comparison of the similarities and differences observed should yield
      valuable insight into the complex network of molecular interactions apparently
      necessary for CD16-mediated NK cell activation.

PMID- 8257829
TI  - Regulation of natural killer function by nonlymphoid cells.
AB  - Natural killer (NK) cells and interleukin-2 activated NK cells, termed lymphokine
      activated killer (LAK) cells, can lyse tumor cells without restriction by the MHC
      complex. The cytotoxic activity of these cells is subject to regulation by
      nonlymphoid cells in vitro. Interaction of NK cells with red blood cells (RBC)
      increases NK cytotoxicity. Interaction with polymorphonuclear neutrophils (PMN)
      suppresses LAK development and also inhibits NK- and LAK-mediated cytotoxicity at
      the effector cell phase. Exposure to tumor necrosis factor-alpha greatly enhances
      the inhibitory effect of PMN at the effector cell phase. Depending on their
      states of activation and differentiation, monocytes have the capacity to either
      enhance or suppress LAK induction. In contrast, macrophages derived from the lung
      are potent inhibitors of NK and LAK activity at both the induction and effector
      cell phases. Several cytokines are secreted by monocytes and macrophages and
      these include both suppressive and enhansive factors of cytotoxic function.
      Platelets are also capable of releasing suppressive factors. NK cells are
      believed to be involved in host surveillance of tumors, control of microbial
      infections and regulation of hematopoiesis. Regulation of NK cells by nonlymphoid
      cells and their products likely provides an in vivo mechanism for locally
      regulating NK function.

PMID- 8257830
TI  - Effect of UV light on tumor cell sensitivity to NK and NC cell-mediated lysis.
AB  - The effect of UV light irradiation on the immunobiological properties of murine
      tumor cells was studied. In vitro irradiation of MCA 102 and MCA 105
      fibrosarcomas with a short-wavelength UVC light rendered them highly immunogenic
      and sensitive to natural cell-mediated cytotoxicity (NCMC). Analysis of the
      effector cells involved in NCMC revealed that UV irradiation stably increased
      tumor cell sensitivity to both NK and NC cell lysis. Studies of the mechanisms
      responsible for increased sensitivity to NK cells indicate that UV treatment did
      not affect tumor-cell recognition by NK cells but increased their susceptibility
      to NK-derived lytic granules. Augmentation of UV-treated tumor cell sensitivity
      to NC cell-mediated lysis was found to be due to their increase in sensitivity to
      the effector-cell-released TNF. In parallel, UV-treated cells showed high
      sensitivity to human recombinant TNF whereas untreated parental cells were
      resistant to rTNF. UV irradiation did not affect rTNF binding, internalization
      and degradation but increased tumor cell vulnerability to TNF-induced DNA
      fragmentation. Thus, UV light appears as a potent modulator of tumor cell
      sensitivity to T cell- and natural cell-mediated immunity.

PMID- 8257831
TI  - Role of NK cell cytotoxic factor against fresh human tumors.
AB  - Blood lymphocytes of cancer patients lysed autologous, freshly isolated tumor
      cells. The autologous tumor-killing (ATK) activity is strongly associated with
      postoperative clinical course, indicating that ATK is a meaningful prognostic
      indicator and provides evidence for immunological control of tumor growth and
      metastasis. Large granular lymphocytes (LGL) with ATK activity released a soluble
      cytotoxic factor(s), termed LGL-CF (LGL-derived cytotoxic factor) during
      interaction with autologous tumor cells. The cytotoxic factor lysed autologous
      and allogeneic freshly isolated human tumor cells, while they were resistant to
      any of recombinant cytokines, including tumor necrosis factor (TNF), lymphotoxin
      (LT), interferon (IFN) alpha, IFN gamma, interleukin (IL)-1 alpha and IL-2.
      Biological activity of LGL-CF was not abrogated by monoclonal and polyclonal
      antibodies against these cytokines. LGL-CF also exhibited lysis of a variety of
      tumor cell lines, but not of nonmalignant cells. Actinomycin D augmented the
      lysis of LGL-CF. LGL-CF was stable at 56 degrees C, but was destroyed at 100
      degrees C. Treatment of LGL-CF with trypsin or proteinase K reduced or abrogated
      the lytic effect, respectively, while it was resistant to papain, catalase, and
      superoxide dismutase. These results indicate that LGL produce a novel cytotoxic
      factor in response to autologous tumor cells that mediates lysis of fresh human
      tumor cells.

PMID- 8257832
TI  - Role of natural killer cells in cancer.
AB  - This paper reviews recent publications and presents data dealing with natural
      killer (NK) cell activity in the tumor-infiltrating lymphocytes (TIL) and
      peripheral blood (PBL) of patients with solid tumors and leukemia. Cells with NK
      markers or function are not a prominent feature of lymphoid infiltrates in solid
      tumors and, when present, do not appear to correlate with other prognostic
      variables. Nevertheless, NK cells among IL-2-activated TIL mediate antitumor
      cytotoxicity. Many studies indicate that NK activity is reduced in patients with
      advanced cancer. In some of these studies, low NK activity has been shown to be
      an unfavorable prognostic variable. PBL, splenic and bone marrow NK activity in
      patients with acute myelogenous leukemia (AML) is also decreased. However,
      adherent IL-2-activated lymphocytes composed primarily of NK cells were found to
      be cytotoxic against AML blasts and could be generated from patients in remission
      and relapse. The question of whether low NK activity in solid tumors and leukemia
      is the result of the disease state or contributes to it, remains unanswered. Data
      are also presented here showing that treated, apparently disease-free patients
      with high PBL NK activity have a significantly longer metastasis-free survival
      time than those with low NK activity (n = 91, p < 0.026, Cox proportional hazards
      test).

PMID- 8257833
TI  - [Chinese material medica combined with cisplatin and lipiodol through
      transcatheter arterial embolization in the treatment of primary hepatoma].
AB  - Transcatheter arterial embolization (TAE) using hydroxycamptothecin, cantharidin
      and cisplatin which were mixed thoroughly with lipiodol, combined with large
      doses interferon and interleukin-2 as adoptive immunotherapy were carried out in
      the treatment of 48 patients with unresectable advanced stage primary hepatoma,
      evaluation of therapeutic effect showed that partial remission rate was 54.2%,
      significantly higher than that of embolization group using chemotherapeutic
      agents alone (cisplatin, adriamycin and mitomycin), the partial remission rate
      was 32.1% (P < 0.01). The side effects of camptothecin and cantharidin including
      hematuria, urodynia were also successfully eliminated.

PMID- 8257834
TI  - [Clinical effects of perfusing drugs into hepatic artery to promote blood
      circulation in late stage of hepatocarcinoma].
AB  - The sophisticated technology of hepatic artery catheterization was used since
      1990 in treating exacerbated patient after chemotherapy, 4-8 ml Salvia
      miltiorrhizae composita injection with 20 ml of 10% glucose was used. The same
      Chinese herbal drug based on Syndrome Differentiation as well as Western drug to
      relieve the symptoms was used in both treated and control groups. After two
      treatment courses, the symptom of treated group was relieved, the tumor mass
      shrunk and the biochemical parameters improved, the total effective rate was 65%,
      while that of control group was 25%, the difference between two groups was very
      significant, P < 0.01. This result suggests that is one of effective methods
      which worth further investigation.

PMID- 8257835
TI  - [Effect of electroacupuncture at zusanli (ST36) point in regulating the pylorus
      peristaltic function].
AB  - The effect of electroacupunture at Zusanli (ST36) point in regulating the human
      pylorus sphincter pressure was investigated in this study by means of the
      endoscopic manometry. The result showed: After electrostimulating Zusanli point,
      the amplitude of the low wave of pylorus sphincter pressure was raised and the
      amplitude of the high wave was reduced significantly while the amplitude of the
      middle wave did not reveal significant change, compared with the results of the
      controls and the non-acupuncture point group. It is indicated that Zusanli point
      may have dual effect on the regulation of the pylorus peristaltic function, which
      expressed itself as enhancing the hypofunction and weakening the hyperfunction of
      pylorus peristalsis.

PMID- 8257836
TI  - [Treatment of 60 cases of HIV-infected patients with glyke].
AB  - 60 HIV-infected patients were treated with Glyke, a Chinese materia medica, 40
      mg, 3 times daily x 3-6 months were given. The total effective rate was 35%. The
      effective + unchanged rate of immune function was 68.3-90%. 18-64% of patients
      improved in clinical symptoms. PCR assay was checked in one of the two
      seronegative patients, it showed positive. Glyke could both inhibit the SIV
      activity as well as enhance the immunity experimentally.

PMID- 8257837
TI  - [Xi xie ting in the treatment of infantile diarrhea].
AB  - In this study, children suffering from viral and dietetic diarrhea were treated
      by bathing their legs and feet with Xi Xie Ting according to the TCM therapeutic
      principle of Clearing Dampness-Heat, eliminating inflammation to stop diarrhea,
      diuresis and regulating the functions of Spleen and Stomach. The results showed
      that there was a significant difference in mean days for disappearance of
      diarrhea between treatment group and control group (P < 0.01). There were
      beneficial effects on curtailing the therapeutic course, reducing the times of
      diarrhea and amount of stool and ameliorating the shape and property of stool.

PMID- 8257838
TI  - [Clinical and experimental studies on membranous pulp-capping agent with Chinese
      medicinal herbs].
AB  - A membranous pulp-capping agent of Chinese medicinal herbs was made by ourselves
      prescription, and was filled in capsules for medication. Direct pulp-capping and
      pulpotomy were performed on 102 permanent teeth. During the observation period of
      more than one year, the successful rate was 82.4%. Under light microscope, the
      artificial exposed sites of normal sheep teeth were fully sealed after capping
      for 45 days. There were calcification under the exposed sites. The inner lines
      were preparative dentins. Experiments on dogs' teeth revealed that the pulps were
      normal after two month's direct pulp-capping, and the new dentins appeared. The
      bacteria culture test was made before and after the pulp-capping agent was used
      on ten deep carious teeth. It revealed that the bacteria all converted negative
      after medication of two weeks. Clinical and experimental studies indicated that
      the pulp-capping agent is valuable in clinical treatment.

PMID- 8257839
TI  - [Effect of suo quan pill for reducing clozapine induced salivation].
AB  - 40 Schizophrenic inpatients with clozapine induced salivation were divided into
      two groups randomly. They were treated with Suo Quan pill and a control study of
      the placebo (neutral pill) for reducing clozapine induced salivation. These cases
      were also classified by TCM Syndrome Differentiation and laboratory examinations
      were performed. RESULTS: There was a significant difference in effect on
      salivation between the therapeutic group (21 cases) and the controlled group (19
      cases), P < 0.01. According to their TCM subtypes two subtypes (Stagnation of
      Phlegm-Dampness and Yin Deficiency) showed the best results. No correlation
      between the peripheral clozapine level and salivation was found. No side effect
      was recorded.

PMID- 8257840
TI  - [Effect of wuzi yanzong liquid on hypothalamus, monoamines, sexual hormones and
      reproductivity in male rats].
AB  - About 100 male SD rats aged 2, 5, 10, 18 and 24 months (each age group for about
      20 rats) were used in the anti-senility experiment. The animals of each age group
      were further subdivided into two groups randomly: one group administered with
      Wuzi Yanzong Liquid (WYL) daily for 5 weeks, and the other group with normal
      saline. After treatment, plasma testosterone (T) and estradiol (E2), hypothalamus
      norepinephrine (NE), dopamine (DA) and serotonin (5-HT) levels were determined.
      In comparison with younger groups, the 18 and 24 months old rats administered
      with saline had markedly lowered plasma T, hypothalamus NE and DA levels, and
      elevated 5-HT, E2 levels and 5-HT/DA, E2/T ratios; while in the 18 and 24 months
      rats administered with WYL the above mentioned changes were much less remarkable.
      Since WYL only raised plasma T level in old rats but not in younger ones, this
      drug seems to have different action from testosterone preparations. In another
      animal experiment, the reproduction promoting effect of WYL was shown by the
      increase of sperm count and motility of sperms in old male rats as well as its
      reproductive ability.

PMID- 8257841
TI  - [Effects of magnesium lithospermate B on D-galactosamine induced rat liver
      injury].
AB  - To investigate the effective ingredients of Salvia miltiorrhizae on anti-liver
      injury, the water soluble component of the above drug, magnesium lithosperamate
      B, was used to conduct the experimental treatment of acute liver injury by D
      galactosamine (10 mg/kg body weight, orally). The results showed that the
      component could obviously attenuate the necrosis of liver tissues, lower the
      activities of serum alanine amino transferase (ALT) and aspartate amino
      transferase (AST), P < 0.05. Compared with those of the normal rats, the levels
      of the products of cyclo-oxygenase (6-keto-prostaglandin F1 alpha, prostaglandin
      D2 and total prostaglandins) in the metabolism of arachidonic acid in non
      parenchymal cells of acute liver-injured rats were markedly decreased (P < 0.05).
      These data revealed that magnesium lithosperamate B might be one of the main
      components of Salvia miltiorrhizae in anti-liver injury, while increasing the
      levels of total prostaglandins in liver non-parenchymal cells was perhaps one of
      the mechanisms of anti-liver injury.

PMID- 8257842
TI  - [Effects of Salvia miltiorrhizae compositae on phosphoinositides metabolism in
      acute myocardial ischemia].
AB  - The effects of Salvia miltiorrhizae compositae (SMC) on phosphoinositides
      metabolism of acute myocardial ischemia in rats were studied. The results showed
      that the function of the phosphoinositide signaling system was enhanced 10 min.
      after acute myocardial ischemia. Both of the accumulations of
      phosphatidylinositol-4,5-biphosphate (PIP2) and inositol-1,4,5-triphosphate (IP3)
      were higher than those of the non-ischemic control group (P < 0.01, n = 7). The
      rise of the levels of PIP2 and IP3 caused by acute myocardial ischemia was
      remarkably inhibited by the SMC (2g/kg body wt.), and the levels of PIP2 and IP3
      were lower than those of the ischemic group (P < 0.01, n = 7).

PMID- 8257843
TI  - [On similarities and differences of kidney yang deficiency and potent energy of
      aged patients based upon the view of internal environment adjustment].

PMID- 8257844
TI  - [Immunosuppressive effect of Tripterygium wilfordii and its application in
      transplantation].

PMID- 8257845
TI  - [Influence of Trpterygium wilfordii on genital organ and sexual hormones].

PMID- 8257846
TI  - Neural glycoproteins: do they provide specific clues for our understanding of
      glycan functions?

PMID- 8257847
TI  - Some comments on the importance of myxoviral glycoproteins.

PMID- 8257848
TI  - Structures of asparagine linked oligosaccharides of immunoglobulins (IgY)
      isolated from egg-yolk of Japanese quail.
AB  - Structures of the Asn linked oligosaccharides of quail egg-yolk immunoglobulin
      (IgY) were determined in this study. Asn linked oligosaccharides were cleaved
      from IgY by hydrazinolysis and labelled with p-aminobenzoic acid ethyl ester
      (ABEE) after N-acetylation. The ABEE labelled oligosaccharides were then
      fractionated by a combination of Concanavalin A-agarose column chromatography and
      anion exchange, normal phase and reversed phase HPLC before their structures were
      determined by sequential exoglycosidase digestion, methylation analysis, HPLC,
      and 500 MHz 1H-NMR spectroscopy. Quail IgY contained only neutral
      oligosaccharides of the following categories: the glucosylated oligomannose type
      (0.6% Glc alpha 1-3Glc alpha 1-3Man9GlcNAc2; 35.6%, Glc alpha 1-3Man7-9GlcNAc2).
      oligomannose type (15.0%, with the structure Man5-9GlcNAc2) and biantennary
      complex type with core structures of -Man alpha 1-3(-Man alpha 1-6)Man beta 1
      4GlcNAc beta 1-4GlcNAc (9.9%), -Man alpha 1-3 (GlcNAc beta 1-4)(-Man alpha 1
      6)Man beta 1-4GlcNAc beta 1-4GlcNAc (25.1%) and -Man alpha 1-3(GlcNAc beta 1-4)(
      Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4(Fuc alpha 1-6)GlcNAc (11.4%). Although
      never found in mammalian proteins, glucosylated oligosaccharides (Glc1Man7
      9GlcNAc2) have been located previously in hen IgY.

PMID- 8257849
TI  - A model for cleavage of O-glycosidic bonds in glycoproteins.
AB  - The present work investigated the possibility of cleavage of alpha-linkages
      between mannose or galactose and serine/threonine residues by alpha-mannosidase
      and alpha-galactosidase. The study was carried out initially with model synthetic
      compounds imitating the O-glycosidic bond in glycoproteins, and further with
      glucoamylase. It was shown that alpha-mannosidase and alpha-galactosidase can
      hydrolyse these linkages after proteolytic digestion of glucoamylase.

PMID- 8257850
TI  - Structure identification of natural rhamnolipid mixtures by fast atom bombardment
      tandem mass spectrometry.
AB  - Two rhamnobiose-lipid preparations have been studied by fast atom bombardment
      (FAB) tandem mass spectrometry. The principal rhamnobiose-lipids contain the beta
      hydroxydecanoyl-beta-hydroxydecanoate Rha-Rha-C10-C10 and the beta
      hydroxytetradecanoyl-beta-hydroxytetradecanoate Rha-Rha-C14-C14. Both
      preparations contain minor components which are heterogenous in beta-hydroxy
      fatty acid composition. FAB ionization of rhamnobiose-lipids in the presence of
      Na+ shows the formation of both [M + Na]+, [M +2Na-H]+, [M + 3Na-2H]+ and [M - H]
      ions. Tandem mass spectrometry of the [M + 2Na-H]+ and [M - H]- ions give
      information about the sequence of the building blocks. Particularly,
      heterogeneity in beta-hydroxy fatty acid composition is determined for the
      principal components and all the minor components present in the preparations.

PMID- 8257851
TI  - Synthetic glycosylation of peptides using unprotected saccharide beta
      glycosylamines.
AB  - Glycopeptides can be valuable tools in determining the influence of carbohydrate
      moieties on the intrinsic properties of glycoproteins. However, glycopeptides of
      sufficient quantity and purity are as yet not readily available from biological
      sources. The chemical coupling of a beta-glycosylamino group of an unprotected
      carbohydrate with an activated aspartic acid residue of an unprotected peptide is
      a simple method for synthesizing asparagine-linked glycopeptides. In this report
      we demonstrate that the use of this method is not restricted to beta
      glycosylamines of simple monosaccharides or short aspartic acid-containing
      pentapeptides. This is illustrated by the syntheses of several glycopentapeptides
      containing N,N'-diacetylchitobiose, a glutamine-linked glycopentapeptide
      containing a biantennary complex oligosaccharide, and glycosylated variants of
      two analogs of a polypeptide hormone, atriopeptin, containing N,N'
      diacetylchitobiose.

PMID- 8257852
TI  - Synthesis of 2,3-di-O-phytanyl-1-O-(alpha-D-glucopyranosyl)-sn-glycerol
      derivatives, analogues of polar lipids isolated from a halophilic bacterial
      strain.
AB  - 2,3-Di-O-phytanyl-1-O-glucopyranosylglycerol and polar derivatives of its 6'
      glucose moiety have been synthesized. The target molecule contains the diphytanyl
      sn-glycerol moiety which is alpha-linked to glucose. The key step in its
      synthesis involves the coupling of phytanyl bromide and isopropylidene threitol.
      We also demonstrated that the 6'-hydroxyl group of glycolipids can be
      functionalized without protection of the sugar moiety.

PMID- 8257853
TI  - Glycosylation of the thrombin-like serine protease ancrod from Agkistrodon
      rhodostoma venom. Oligosaccharide substitution pattern at each N-glycosylation
      site.
AB  - In a previous study, we determined the structures of the glycans present in
      ancrod, a thrombin-like serine protease from the venom of the Malayan pit viper
      Agkistrodon rhodostoma (Pfeiffer et al. (1992) Eur J Biochem 205:961-78). In
      order to allocate the various carbohydrate chains to distinct N-glycosylation
      sites of the molecule, we have now isolated individual glycopeptides. Peptide
      moieties were identified after deglycosylation with peptide-N4-(N-acetyl-beta
      glucosaminyl)asparagine amidase F by amino acid analysis and sequencing.
      Liberated oligosaccharides were assigned to the previously deduced carbohydrate
      structures by high performance liquid chromatography. Although only quantitative
      differences were observed, the results indicate that each glycosylation site of
      ancrod carries its characteristic oligosaccharide pattern. Furthermore, all
      potential sites were shown to be substituted by carbohydrates.

PMID- 8257854
TI  - Developmental changes in neutral glycosphingolipids of mouse placenta.
AB  - The mammalian placenta is a unique organ for the study of developmental changes.
      Placentas of laboratory animals such as the mouse allow for the determination of
      the exact stage of pregnancy, which cannot be achieved with human placenta. In
      this study, neutral glycosphingolipids were isolated from mouse (inbred strain
      C57BL/6) placentas, from day 10 to day 18 of gestation, and were separated by
      high performance thin layer chromatography. Densitometric measurements after
      orcinol staining showed, at day 10 of gestation, the presence of mono-, tetra-,
      tri- and dihexosylceramide in decreasing quantities, as well as four unidentified
      spots. On day 12, the glycosphingolipid composition changed with the
      disappearance of the unidentified spots and the appearance of an orcinol positive
      migrating similarly to the Forssman antigen; no further changes occurred between
      days 12 and 18 of gestation. The identity of the Forssman-like glycosphingolipid
      with the Forssman antigen was established by binding of 125I labelled Helix
      pomatia agglutinin (alpha-GalNAc specific) to glycosphingolipids separated on
      high performance thin layer chromatography plates, and by the reaction of the
      isolated glycosphingolipid with a monoclonal anti-Forssman antibody. The
      appearance of the Forssman antigen at day 12 of gestation coincided with the day
      of final maturation of the mouse placenta and subsequent cessation of growth,
      suggesting a possible role of the glycosphingolipid during embryonic development.

PMID- 8257855
TI  - The role of cytokines in the development of autoimmune thyroid disease.

PMID- 8257856
TI  - Pathogenesis of autoimmune hypothyroidism induced by lymphokine-activated killer
      (LAK) cell therapy: in vitro inhibition of human thyroid function by interleukin
      2 in the presence of autologous intrathyroidal lymphocytes.
AB  - Lymphokine-activated killer (LAK) cell therapy frequently results in primary
      hypothyroidism. To elucidate the responsible mechanism, we investigated the
      effects of interleukin-2 (IL-2) on thyroid function of cultured human thyroid
      follicles in the presence or absence of autologous thyroid-derived lymphoid cells
      (TDLC). Human thyroid follicles, obtained by subtotal thyroidectomy from patients
      with Graves' disease, were cultured in serum-free medium containing bTSH and
      various concentrations of human IL-2, with or without TDLC. After 5 days of
      culture, 125I was added, and after an additional 3 days of culture, 125I
      incorporated into thyroid follicles and organic 125I (125I-T4 + 125I-T3) released
      into the culture medium were estimated. In the absence of TDLC, IL-2 did not
      affect bTSH-induced thyroid function. In the presence of TDLC, however, IL-2
      inhibited the bTSH-stimulated thyroid function in a concentration-dependent
      manner. The minimum IL-2 concentration required to inhibit thyroid function was 1
      U/ml. At 100 U/ml, IL-2 inhibited thyroid function completely. IL-2 increased the
      concentration of IFN-gamma in the culture medium conditioned by TDLC but not by
      thyroid follicles. When both were cocultured, IL-2 more significantly increased
      the concentration of IFN-gamma to an extent sufficient for inhibiting thyroid
      function per se. Furthermore, the addition of anti-IFN-gamma antibody to the
      medium partially restored the IL-2-inhibited thyroid function. In summary, by
      coculturing human thyroid follicles and autologous intrathyroidal lymphocytes
      with IL-2, it was possible to reproduce the thyroid dysfunction associated with
      LAK cell therapy. Our data indicate that IL-2 inhibits thyroid function, at least
      partly, by stimulating production of IFN-gamma, a potent inhibitory cytokine for
      thyroid cells.

PMID- 8257857
TI  - Crucial role of serum human chorionic gonadotropin for the aggravation of
      thyrotoxicosis in early pregnancy in Graves' disease.
AB  - Thyrotoxicosis in Graves' disease is often aggravated in early pregnancy and is
      closely associated with postpartum recurrence of stimulative thyrotoxicosis. To
      examine whether thyroid-stimulating TSH receptor antibody (TSAb) or human
      chorionic gonadotropin (hCG), which also has thyroid-stimulating activity (TSA),
      was responsible for this early aggravation, the respective TSA due to TSAb or hCG
      was evaluated by a highly sensitive cAMP accumulation assay using FRTL-5 cells.
      TSA was detectable in all of 11 women in normal early pregnancy, correlated
      positively with serum hCG concentration, and was abolished completely by the
      pretreatment of serum sample with the solid-phase hCG antibody coupled with
      Sepharose 4B. The model serum samples of Graves' disease with pregnancy were made
      by the mixture of normal pregnant and Graves' sera, and their TSA were reduced by
      the pretreatment with the solid-phase hCG antibody, just corresponding with the
      reduction in hCG-induced TSA. TSA of early pregnant sera in 20 patients with
      Graves' disease decreased significantly but were still positive even after the
      pretreatment with the hCG antibody. Serial changes in TSAb and hCG-induced TSA
      were measured in 5 of these 20 pregnant patients. hCG-induced TSA increased
      associated with the increase in free thyroxine, while TSAb did not show striking
      change in early pregnancy. These data indicate that (1) respective TSA due to
      TSAb or hCG can be measured distinctively by using the solid-phase hCG antibody
      and (2) hCG plays a crucial role in the aggravation of Graves' thyrotoxicosis in
      early pregnancy.

PMID- 8257858
TI  - Positron emission tomography of thyroid masses.
AB  - Nine patients with suspicious thyroid nodules were studied with positron emission
      tomography (PET) following the administration of [18F]-2-deoxy-2-fluoro-D-glucose
      (FDG) prior to surgical excision. Three patients were ultimately determined to
      have papillary carcinoma, four were shown to have follicular adenomas, and two
      were proven to have multinodular goiters with dominant nodules. All three
      malignancies and four of the six benign lesions were easily detected visually as
      areas of increased FDG uptake. While visual analysis alone did not discriminate
      between the benign and malignant lesions, all three malignancies had dose uptake
      ratios (DURs) for FDG in excess of 8.5 while the DURs for benign lesions ranged
      between 1.9 and 6.3. The mean FDG DUR for the three papillary carcinomas (10.9 +/
      3.9; mean +/- SD) was significantly greater (p = 0.0019) than that of the six
      benign lesions (3.2 +/- 1.7). There was no significant difference between the FDG
      DUR for the follicular adenomas and the dominant nodules of multinodular goiters.
      Further research is needed to confirm the usefulness of PET in the differential
      diagnosis of thyroid nodules, and, in particular, whether or not PET can
      discriminate between benign and malignant follicular neoplasms.

PMID- 8257859
TI  - Pulsatile TSH secretion during 48-hour continuous TRH infusions.
AB  - Thyroid-stimulating hormone (TSH), like other anterior pituitary hormones, is
      normally secreted in a series of pulses over 24 h. However, the factors that
      control TSH pulse generation are unknown. We investigated the potential role of
      thyrotropin-releasing hormone (TRH) in TSH pulse generation by measuring TSH
      pulses during constant TRH infusions. Two groups of subjects were studied: five
      healthy subjects and five subjects with treated primary hypothyroidism and normal
      TSH levels. Each subject underwent four separate studies: (1) TSH levels were
      measured every 15 min over 24 h (baseline study). (2) TSH levels were measured
      every 15 min over 48 h during TRH infusions at 0.1 microgram/min (low dose TRH
      study). (3) TSH levels were measured every 15 min over 48 h during TRH infusion
      at 0.5 microgram/min (medium dose TRH study). (4) TSH levels were measured every
      15 min over 48 h during TRH infusions at 1.0 microgram/min (high dose TRH study).
      TSH pulses were located by cluster analysis. We found that constant TRH infusions
      at any of the doses utilized did not alter TSH pulse frequency in normal or
      treated hypothyroid subjects, although pulse amplitude increased. Normal subjects
      had lower TSH pulse amplitude than treated hypothyroid subjects at all TRH doses,
      perhaps due to slightly higher serum T3 levels. This suggests that, at least
      acutely, pulsatile input of TRH to the pituitary gland does not determine
      pulsatile TSH release. However, TRH may modulate TSH pulse amplitude.

PMID- 8257860
TI  - Analysis of fibroblast-stimulating activity in IgG from patients with Graves'
      dermopathy.
AB  - Conflicting results have been reported on the effect of IgGs from patients with
      Graves' dermopathy on dermal fibroblast function. We have analyzed 14 dermopathy
      IgGs prepared by protein G affinity chromatography. These caused FRTL-5 thyroid
      cells to synthesize significantly greater amounts of glycosaminoglycans (GAG) and
      protein than IgGs from normal controls (p < 0.05). [3H]Thymidine incorporation
      was also significantly increased (p < 0.05) and there was a significant
      correlation between all three parameters and the ability of these IgGs to
      stimulate iodide incorporation (p < 0.001). Dermopathy and control IgGs caused a
      modest increase in GAG synthesis by dermal fibroblasts but there was no
      significant difference between the two types of IgG. Increased GAG production was
      detectable in both culture medium and the extracellular matrix, and there was no
      difference between fibroblasts derived from the arm and leg. Conditioned medium
      from thyroid cells treated with dermopathy or control IgGs caused a greater
      increase in GAG production than the IgGs alone, but again there was no difference
      between the two sources of IgG. Neither control nor dermopathy IgG affected
      fibroblast protein synthesis or [3H]thymidine incorporation. Our results argue
      against a role for circulating IgGs in mediating Graves' dermopathy and make it
      unlikely that the TSH receptor antibodies are acting directly on a functional
      receptor expressed by dermal fibroblasts in this disorder.

PMID- 8257861
TI  - Basal and thyrotropin-stimulated secretion rates of thyroglobulin from the human
      thyroid gland during surgery.
AB  - The secretion rates of thyroglobulin were measured under basal conditions and
      after exogenous and endogenous thyrotropin stimulation in 23 patients during
      surgery. In 11 patients with normal thyroid glands the median secretion rate of
      thyroglobulin was 0.7 pmol/24 h. Higher secretion rates were observed in 8
      patients with nontoxic nodular goiter (median 22 pmol/24 h; p < 0.001) and in 4
      patients with thyroid malignancy (median 2.2 pmol/24h; p < 0.05). Within 10 min
      after administration of highly purified human thyrotropin into the thyroid artery
      an increase of the secretion rates was observed in the 9 patients studied with
      normal thyroid glands and 5 patients with nontoxic nodular goiter. TRH
      administration to 5 patients induced a slight but nonsignificant increase of the
      secretion rate of thyroglobulin after 20 min. These results show that
      thyroglobulin is secreted directly into the thyroid venous blood. They also
      confirm that thyrotropin is an important regulator of the thyroglobulin
      secretion.

PMID- 8257862
TI  - Liquid hybridization analysis of TSH receptor mRNA in normal and abnormal human
      thyroid tissues.
AB  - Radiolabeled human TSH receptor (hTSHR) cRNA probes encoding nucleotides 37-2298
      and 37-209, with unlabeled sense RNA control segments, were used in a liquid
      hybridization assay and found to be highly specific and sensitive enabling
      detection of 0.5 fmol of hTSHR mRNA. Using normal human thyroid monolayer cell
      cultures we calculated that the average number of TSHR mRNA transcripts was 95 +/
      5 per cell under in vitro basal conditions. We found no significant difference
      between the hTSHR mRNA concentrations of intact normal human thyroid tissue (n =
      4) and specimens from patients with multinodular goiter (n = 5) and Graves'
      disease thyroid tissues (n = 5) (23.0, 25.2, and 27.6 fmol of hTSHR and mRNA/mg
      total cellular RNA, respectively). However, there was a relative deficiency of
      hTSHR mRNA in some samples of thyroid papillary carcinoma tissue (n = 5) (12 fmol
      of hTSHR mRNA/mg total RNA, p < 0.05). The hTSHR 37-2298 probe was fully
      protected in normal and abnormal thyroid tissues, consistent with the absence of
      large deletions or insertions in the hTSHR mRNA transcripts but additional bands
      were present, consistent with the production of splicing variants.

PMID- 8257863
TI  - Is TPO detectable in the circulation?
AB  - Recent reports have suggested that thyroid peroxidase (TPO) can be detected in
      the circulation of normal subjects and of patients with Graves' disease and we
      have attempted to confirm and extend these observations. A TPO radioimmunoassay
      with a sensitivity of 1 ng/mL was used to measure TPO in the sera from 20 normal
      subjects and 21 patients with Graves' disease. In addition, TPO was measured in
      serum samples from six normal subjects before and after oral TRH. We were unable
      to detect TPO in 46 out of the 47 sera studied (normals and autoimmune thyroid
      disease). In the one remaining serum (from a normal subject), low levels of TPO
      were apparently detected, but we demonstrated that this result was due to assay
      interference from TPO autoantibodies. Overall our studies suggest that (1)
      thyroid peroxidase is not detectable in normal subjects nor in TPO autoantibody
      negative patients with Graves' disease; (2) endogenous TPO autoantibodies can
      interfere in the TPO radioimmunoassay leading to false positive results; and (3)
      an acute increase of TSH in normal subjects does not result in TPO release into
      the circulation.

PMID- 8257864
TI  - Urinary cortisol metabolites in the assessment of peripheral thyroid hormone
      action: application for diagnosis of resistance to thyroid hormone.
AB  - Urinary cortisol metabolites are altered both quantitatively and qualitatively in
      thyroid dysfunction. This study was conducted to elucidate the usefulness of
      urinary cortisol metabolites in the assessment of peripheral thyroid hormone
      action, particularly in the patients with inappropriate thyrotropin secretion.
      Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) level and gas
      chromatographical steroid profile were studied in 25 hyperthyroid, 18
      hypothyroid, and 24 euthyroid control subjects. Five patients with generalized
      thyroid hormone resistance and two patients with thyrotropin secreting pituitary
      tumor were also studied. The ratio of urinary tetrahydrocortisone to
      tetrahydrocortisol (THE/THF) was significantly elevated in hyperthyroidism (4.58
      +/- 1.49) and depressed in hypothyroidism (1.31 +/- 0.55) compared to control
      (1.93 +/- 0.35). There were good correlations between THE/THF and serum thyroid
      hormone levels, especially in hypothyroidism. THE/THF can be a good biochemical
      indicator for deficiency of peripheral thyroid hormone action. Two patients with
      thyrotropin-secreting tumor showed high THE/THF, which reflected thyroid hormone
      excess. In contrast, THE/THF in the patients with generalized thyroid hormone
      resistance was low as compared to high serum thyroid hormone levels. Similar
      findings were demonstrated with 17-OHCS but discrimination of thyroid hormone
      resistance was insufficient. Thus, the ratio of the urinary concentrations of
      cortisol metabolites, THE/THF, appears to be a good marker for peripheral thyroid
      hormone resistance.

PMID- 8257865
TI  - Cutaneous metastasis from follicular carcinoma of the thyroid gland.
AB  - A 65-year-old man with a history of malignant melanoma presented a reddish nodule
      on the left temporal region of the scalp. Histologic features and
      immunoperoxidase staining on the skin biopsy specimen confirmed the diagnosis of
      metastatic thyroid follicular carcinoma. The patient presented recurrences of
      metastatic skin nodules, lung and bone metastases, and died after a 3-year follow
      up.

PMID- 8257866
TI  - Iodine regulation of endothelin-1 gene expression in cultured porcine thyroid
      cells: possible involvement in autoregulation of the thyroid.
AB  - We studied the regulation of endothelin (ET)-1 gene expression in porcine thyroid
      cells in culture. First, we demonstrated prepro-ET-1 mRNA in porcine thyroid
      cells. The level of the mRNA was increased by phorbol 12-myristate 13-acetate
      (TPA), a protein kinase C stimulator, but was decreased by TSH (1 mU/mL).
      However, transforming growth factor-beta and interleukin-1 beta had no effect.
      The amount of immunoreactive (ir)-ET-1 secreted from the cells was also increased
      by TPA and was decreased by TSH. Next, we studied the effect of iodide, as iodide
      has various effects on thyroid cells. NaI (100 microM) increased the prepro-ET-1
      mRNA level. The effect of NaI was attenuated by 1 mM methimazole (MMl). The
      amount of ir-ET-1 released from the cells was also increased by the NaI treatment
      and the increase was also attenuated by MMl. These observations indicate that ET
      1 gene expression is induced by organified iodine compounds in thyroid cells in a
      manner very similar to the inhibitory actions of iodide on thyroid cell function.
      The protein synthesis inhibitor, cycloheximide, superinduced prepro-ET-1 mRNA
      within 4 h, but NaI did not. The difference between cycloheximide and NaI
      suggests that the iodine effect on the gene expression is not due to nonspecific
      inhibition of protein synthesis. Together with our previous findings that porcine
      thyroid cells have ET-1 receptors and that ET-1 modulates iodine metabolism, we
      speculate that ET-1 produced by thyroid cells is involved in thyroid
      autoregulation including thyroid blood flow.

PMID- 8257867
TI  - 1,25-dihydroxyvitamin D3 attenuates TSH and 8-(4-chlorophenylthio)-cAMP
      stimulated growth and iodide uptake by rat thyroid cells (FRTL-5).
AB  - The effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on TSH and the 3',5'
      cyclic adenosine monophosphate (cAMP) analogue 8-(4-chlorophenylthio)-cAMP
      stimulated cell growth and iodide uptake were studied in a rat thyroid cell line
      (FRTL-5). 1,25-(OH)2D3 inhibited both TSH and 8-(4-chlorophenylthio)-cAMP-induced
      cell proliferation with the maximum effect at 100 nmol/L. The inhibitory effect
      of 1,25-(OH)2D3 (10 nmol/L) on TSH and 8-(4-chlorophenylthio)-cAMP-stimulated
      iodide uptake was observed after 2 days of incubation, and the effect was maximal
      after 4 days. The inhibition was dose-dependent and maximal at 100 nmol/L 1,25
      (OH)2D3. 1,25-(OH)2D3 (10 nmol/L, 4 days) increased the median concentrations of
      TSH required to stimulate both cAMP production and iodide uptake half-maximally
      by 124 and 187%, respectively, whereas the median 8-(4-chlorophenylthio)-cAMP
      concentration was not changed. Lineweaver-Burke plots revealed that 1,25-(OH)2D3
      reduced the Vmax of the sodium-driven iodide carriers to 30% of the control cells
      without effect on the Km. Iodide efflux was only slightly increased in the 1,25
      (OH)2D3-treated cells. In conclusion, 1,25-(OH)2D3 potently inhibited the TSH
      stimulated growth and iodide uptake by FRTL-5 cells both by reducing the TSH
      stimulated cAMP production and by attenuating the stimulatory effects of cAMP.

PMID- 8257868
TI  - The management of subacute (DeQuervain's) thyroiditis.
AB  - Subacute (DeQuervain's) thyroiditis is a transient inflammatory thyroid disease
      usually associated with pain and tenderness of the gland, as well as generalized
      somatic symptoms, which can cause great discomfort or even complete prostration
      for weeks or months if left untreated. It is almost certainly the result of a
      viral infection. There is no definitive therapy for painful subacute thyroiditis,
      but there is effective treatment that will ameliorate the symptoms and allow the
      disease to run its spontaneous course in an asymptomatic fashion. Salicylates and
      nonsteroidal antiinflammatory drugs can be used in patients with mild or moderate
      forms of the disorder. In more severe forms of the condition, corticosteroids in
      suitable pharmacological dosage will generally cause a rapid relief of symptoms
      within 24-48 h. Prednisone may be initiated in dosages of 40 mg daily, with a
      gradual reduction in dosage thereafter over several weeks. Recurrences do appear
      in a small percentage of patients, necessitating restoration of a higher dose
      once again. Repeat exacerbations are uncommon. Other less common forms of
      treatment include triiodothyronine or thyroxine, generally to prevent repeated
      exacerbations. Irradiation is no longer employed. Thyroidectomy should be
      considered only in that very small minority of patients who have repeated
      relapses despite appropriate treatment. During the period of transient
      hypothyroidism, thyroxine may be provided but can usually be discontinued
      subsequently. General recovery is almost the universal rule and only less than 1%
      become permanently hypothyroid.

PMID- 8257869
TI  - Chronic nicotine reverses working memory deficits caused by lesions of the
      fimbria or medial basalocortical projection.
AB  - Nicotine has been found in a variety of studies to improve performance in memory
      tasks. This study was conducted to determine if chronic nicotine administration
      is useful in counteracting the working memory deficits seen after lesions of the
      fimbria or the medial basalocortical projection. Rats were trained to asymptotic
      performance on a working memory version of the radial-arm maze. Then, they were
      given knife cut lesions of the fimbria or the medial basalocortical projection or
      underwent sham surgeries. At the time of surgery, rats in each treatment group
      were implanted with either nicotine-containing or placebo glass and Silastic
      pellets. Rats with fimbria or basalocortical lesions showed a significant decline
      in working memory performance. Chronic nicotine significantly improved choice
      accuracy in both lesioned and unlesioned rats. Nicotine treatment restored
      performance of the lesioned rats to control levels. These data show that in
      addition to improving memory performance in normal rats, nicotine can counteract
      lesion-induced memory impairments. Nicotine also may be useful for treatment of
      disease-related memory impairments such as seen in Alzheimer's disease.

PMID- 8257870
TI  - Topographic differences of slow event-related brain potentials in blind and
      sighted adult human subjects during haptic mental rotation.
AB  - Twelve blindfolded sighted, nine congenitally blind, and seven adventitiously
      blind subjects were tested in a haptic mental rotation task while slow event
      related brain potentials in the EEG were recorded from 17 scalp locations. The
      overall topography of the slow wave pattern which prevailed during the task
      differed for sighted and for blind, but not for congenitally and adventitiously
      blind subjects. While the tactile stimuli were encoded, the blind showed a
      pronounced occipital and the sighted a pronounced frontal activation. The task
      specific amplitude increment of a negative slow wave which can be understood as a
      manifestation of the process of mental rotation proper, showed a different
      topography for sighted and for blind subjects too. It had its maximum over
      central to parietal cortical areas in both groups, but it extended more towards
      occipital regions in the blind. In both groups, the effects were very similar to
      those observed in former studies with visual versions of the mental rotation
      task, i.e. the slow wave amplitude over central to parietal areas increased
      monotonously with an increasing angular disparity of the two stimuli to be
      compared. These results are discussed with respect to the question of whether
      visual deprivation in the blind can cause a reorganization of cortical
      representational maps.

PMID- 8257871
TI  - The effects of age on the N200 component of the auditory event-related
      potentials.
AB  - This study was undertaken to determine the effects of development and aging on
      N200 of event-related potentials from childhood to adulthood. Event-related
      potentials were recorded from 164 normal subjects ranging in age from 4 to 77
      years. A total of 127 of the 164 subjects demonstrated N200 peaks. N200 showed
      marked developmental changes. During childhood, the N200 latency decreased
      rapidly with age to the minimum (217 +/- 17.3 ms) at 16 years of age, while it
      was prolonged gradually with age during adulthood. The latency/age slope in the
      subjects from 5 to 15 years of age was -9.03 ms/year, while +0.97 ms/year in
      those from 16 to 77. The N200-P300 interpeak latency remained constant in all age
      groups and showed no age-related changes. The N200 amplitude decreased as age
      increased. Nineteen young cases showed N200 peaks to the frequent stimuli. Their
      ages ranged from 5 to 17 years. Our study suggests that N200 is valuable in
      evaluating the developmental and aging processes in the central nervous system.
      The results of this study could be used as normative data in clinical practices.

PMID- 8257872
TI  - Motion-onset visual-evoked potentials as a function of retinal eccentricity in
      man.
AB  - Visual-evoked potentials were elicited by the motion-onset of a black-and-white
      square-wave grating of 2.4 cycles/deg that drifted from right to left at a
      velocity of 3 deg/s. The center of the 2 x 2 deg stimulus field was binocularly
      viewed either foveally or at eccentricities of 6, 12, or 20 deg in the lower
      visual field along the vertical meridian. Peak-to-peak amplitudes P1-N2 and N2-P2
      were found to decrease non-linearly as a function of eccentricity. The VEP
      amplitudes were standardized by setting each foveal value to 100%, and a relative
      measure was derived for peripheral values given by the ratio of the peripheral to
      the foveal values. The decrease of the relative VEP-values with eccentricity was
      significantly smaller than that of the relative cortical magnification factor of
      striate cortex in man, whereas it agreed fairly well with that of the relative
      point-image size of the area MT in Macaque monkey. In this respect, the motion
      onset VEP is distinct from the pattern-reversal VEP, the amplitude of which
      decreases much more rapidly with retinal eccentricity; hence, it may involve
      different generating structures of the brain.

PMID- 8257873
TI  - A dynamical analysis of oscillatory responses in the optic tectum.
AB  - Multi-unit recordings from the optic tectum of an awake pigeon displaying
      oscillatory behavior evoked by visual stimulus are highly non-stationary and
      contain a broad band of frequencies under a time-window analysis. Here we extend
      these observations by a non-linear dynamical analysis of these oscillatory
      signals (local fields potentials) in successive epochs during background activity
      and visual responses. Two numerical estimates have been obtained from the
      original data every 200 ms: (1) correlation dimension and (2) non-linear
      forecasting of the trajectories. Results from eight different recording sites
      analyzed are consistent and indicate, in the average, an increase in complexity
      of the signal during the oscillatory periods.

PMID- 8257874
TI  - Event-related brain potentials during natural speech processing: effects of
      semantic, morphological and syntactic violations.
AB  - The present study investigated different aspects of auditory language
      comprehension. The sentences which were presented as connected speech were either
      correct or incorrect including a semantic error (selectional restriction), a
      morphological error (verb inflection), or a syntactic error (phrase structure).
      After each sentence, a probe word was presented auditorily, and subjects had to
      decide whether this word was part of the preceding sentence or not. Event-related
      brain potentials (ERPs) were recorded from 7 scalp electrodes. The ERPs evoked by
      incorrect sentences differed significantly from the correct ones as a function of
      error type. Semantic anomalies evoked a 'classical' N400 pattern. Morphological
      errors elicited a pronounced negativity between 300 and 600 ms followed by a late
      positivity. Syntactic errors, in contrast, evoked an early negativity peaking
      around 180 ms followed by a negativity around 400 ms. The early negativity was
      only significant over the left anterior electrode. The present data demonstrate
      that linguistic errors of different categories evoke different ERP patterns. They
      indicate that with using connected speech as input, different aspects of language
      comprehension processes cannot only be described with respect to their temporal
      structure, but eventually also with respect to possible brain systems subserving
      these processes.

PMID- 8257875
TI  - Chronometrical analysis of event-related potentials and reaction time in patients
      with multiple lacunar infarcts.
AB  - We measured the visual event-related potentials (ERPs) and reaction time (RT) in
      31 patients with multiple lacunar infarcts and 18 age-equivalent normal subjects.
      The N2 and RT latencies of the patients were significantly longer than those of
      normal subjects, although P2 and P3 latencies did not differ between the two
      groups. However, the time from N2 to RT did not differ between the two groups.
      These observations suggest that the impairment of cognitive information
      processing in these patients arises from an uncertainty in classifying the
      perceived event, while motor organization time is relatively well preserved. In
      addition, the N2 latency may be more sensitive in detecting cognitive impairment
      in such patients.

PMID- 8257876
TI  - Intensity to force translation: a new effect of stimulus-response compatibility
      revealed by analysis of response time and electromyographic activity of a prime
      mover.
AB  - In reaction time studies of stimulus-response compatibility, emphasis has been
      placed on the influence of spatial stimulus-response relationships, but what
      seems to be essential for the emergence of an effect of stimulus-response
      compatibility is the existence of a conceptual match between stimulus and
      response variables. This notion was at the origin of the present study to assess
      the compatibility relationship between the intensity of a visual stimulus and the
      force of a voluntary muscle contraction. A stimulus-response compatibility effect
      was demonstrated. This effect was entirely due to premotoric processes.

PMID- 8257877
TI  - Supporting the injured lung.

PMID- 8257878
TI  - Lessons from measles vaccination in developing countries.

PMID- 8257879
TI  - Ethnic composition of NHS boards.

PMID- 8257880
TI  - Publishing the results of sponsored clinical research.

PMID- 8257881
TI  - Managing stroke: the way forward.

PMID- 8257882
TI  - Repetitive strain injury.

PMID- 8257883
TI  - Access to coronary catheterisation: fair shares for all?
AB  - OBJECTIVE: To determine the effects of patient's sex and area's material
      deprivation on utilisation rates of coronary catheterisation and angiography in
      the investigation of ischaemic heart disease. DESIGN: Retrospective analysis of
      routinely collected hospital statistics. SETTING: Acute hospitals throughout
      Northern Ireland. SUBJECTS: 24,179 episodes of patients discharged from hospital
      with a primary diagnosis of ischaemic heart disease and 1270 episodes relating to
      patients with an underlying diagnosis of ischaemic heart disease who had either
      coronary catheterisation or angiography. MAIN OUTCOME MEASURES: Age standardised
      admission rates for heart disease and age standardised utilisation rates for
      catheterisation or angiography, or both, for 566 electoral wards ranked by
      Townsend "deprivation" scores. RESULTS: Catheterisation-angiography rates in men
      were over fivefold those of women, ranging from 85.5/100,000 v 16/100,000 in
      patients from "well off" areas to 123/100,000 v 22/100,000 for patients from
      deprived areas. After admission rates for heart disease were controlled for, the
      overall rate ratio for women was 0.48 (95% confidence interval 0.38 to 0.60).
      After differential admission rates for heart disease and other potential clinical
      confounders were controlled for, the investigation rates of patients from the
      least and most "deprived" areas were not significantly different (rate ratio 1.04
      (0.87 to 1.25)). CONCLUSION: Although investigation rates were significantly
      lower in women than in men, further clinical data would be required before
      labelling this underutilisation as evidence of bias. There was no significant
      difference in invasive investigation rates for heart disease in areas of varying
      deprivation or affluence.

PMID- 8257884
TI  - Reduced childhood mortality after standard measles vaccination at 4-8 months
      compared with 9-11 months of age.
AB  - OBJECTIVE: To evaluate the impact on mortality of standard Schwarz measles
      immunisation before 9 months of age. DESIGN: Children vaccinated in 1980-3 at 4
      5, 6-8, and 9-11 months of age were followed to migration, death, or the age of 5
      years. SETTING: One urban district and nine villages in two rural areas of Guinea
      Bissau. SUBJECT: 307 children vaccinated at 4-8 months and 256 at 9-11 months.
      MAIN OUTCOME MEASURES: Mortality from 9 months to 5 years of age for children
      immunised at 4-5, 6-8, and 9-11 months. RESULTS: Mortality was significantly
      lower in children vaccinated at 6-8 months than at 9-11 months (mortality ratio =
      0.63, (95% confidence interval 0.41 to 0.97), p = 0.047). As vaccination was
      provided in semiannual or annual campaigns it is unlikely that age at vaccination
      reflected a selection bias. The trend was the same in all three study areas.
      Improved survival after early immunisation was not related to better protection
      against measles infection. With a Cox multivariate regression model to adjust for
      age, sex, season at risk, season at birth, measles infection, and region,
      children vaccinated at 4-8 months had a mortality ratio of 0.61 (0.40 to 0.92, p
      = 0.020) compared with children vaccinated at 9-11 months. Reimmunised children
      tended to have lower mortality than children who received only one vaccine (0.59
      (0.28 to 1.27, p = 0.176)). CONCLUSION: Standard measles vaccination before 9
      months is not associated with higher childhood mortality than is the currently
      recommended strategy of immunising from 9 months, and it may reduce mortality.
      This has implications for measles immunisation strategy in developing countries.

PMID- 8257885
TI  - Bed sharing, smoking, and alcohol in the sudden infant death syndrome. New
      Zealand Cot Death Study Group.
AB  - OBJECTIVES: To investigate why sharing the bed with an infant is a not consistent
      risk factor for the sudden infant death syndrome in ethnic subgroups in New
      Zealand and to see if the risk of sudden infant death associated with this
      practice is related to other factors, particularly maternal smoking and alcohol
      consumption. DESIGN: Nationwide case-control study. SETTING: Region of New
      Zealand with 78% of all births during 1987-90. SUBJECTS: Home interviews were
      completed with parents of 393 (81.0% of total) infants who died from the sudden
      infant death syndrome in the postneonatal age group, and 1592 (88.4% of total)
      controls who were a representative sample of all hospital births in the study
      region. RESULTS: Maternal smoking interacted with infant bed sharing on the risk
      of sudden infant death. Compared with infants not exposed to either risk factor,
      the relative risk for infants of mothers who smoked was 3.94 (95% confidence
      interval 2.47 to 6.27) for bed sharing in the last two weeks and 4.55 (2.63 to
      7.88) for bed sharing in the last sleep, after other confounders were controlled
      for. The results for infants of non-smoking mothers were inconsistent with the
      relative risk being significantly increased for usual bed sharing in the last two
      weeks (1.73; 1.11 to 2.70) but not for bed sharing in the last sleep (0.98; 0.44
      to 2.18). Neither maternal alcohol consumption nor the thermal resistance of the
      infant's clothing and bedding interacted with bed sharing to increase the risk of
      sudden infant death, and alcohol was not a risk factor by itself. CONCLUSION:
      Infant bed sharing is associated with a significantly raised risk of the sudden
      infant death syndrome, particularly among infants of mothers who smoke. The
      interaction between maternal smoking and bed sharing suggests that a mechanism
      involving passive smoking, rather than the previously proposed mechanisms of
      overlaying and hyperthermia, increases the risk of sudden infant death from bed
      sharing.

PMID- 8257886
TI  - Non-fasting serum triglyceride concentration and mortality from coronary heart
      disease and any cause in middle aged Norwegian women.
AB  - OBJECTIVE: To study the association between non-fasting serum triglyceride
      concentrations and mortality in women from coronary and cardiovascular disease
      and all causes. DESIGN: Follow up by ambulatory teams of men and women who
      underwent cardiovascular screening for a mean of 14.6 years. SETTING: National
      health screening service in Norway. SUBJECTS: 25,058 men and 24,535 women aged 35
      49 years. MAIN OUTCOME MEASURE: Predictive value of non-fasting serum
      triglyceride concentrations. RESULTS: At initial screening total serum
      cholesterol concentration, serum triglyceride concentration, blood pressure,
      height, and weight were measured, and self reported information about smoking
      habits, physical activity, and time since last meal were recorded. During
      subsequent follow up 108 women died from coronary heart disease, 238 from
      cardiovascular diseases, and 931 from all causes. In women mortality increased
      steadily with increasing triglyceride concentration for all three causes of
      death. With the proportional hazards model and adjustment for age, systolic blood
      pressure, total cholesterol concentration, time since last meal, and number of
      cigarettes a day the relative risk between triglyceride concentration > or = 3.5
      mmol/l and < 1.5 mmol/l was 4.7 (95% confidence interval 2.5 to 8.9) for deaths
      from coronary heart disease, 3.0 (1.9 to 4.8) for deaths from cardiovascular
      disease, 2.3 (1.8 to 2.9) for total deaths in all women. CONCLUSIONS: A raised
      non-fasting concentration of triglycerides is an independent risk factor for
      mortality from coronary heart disease, cardiovascular disease, and any cause
      mortality among middle aged Norwegian women in contrast to what is seen in men.

PMID- 8257887
TI  - Cost effectiveness analysis of early zidovudine treatment of HIV infected
      patients.
AB  - OBJECTIVE--To compare cost effectiveness of early and later treatment with
      zidovudine for patients infected with HIV. DESIGN--Markov chain analysis of cost
      effectiveness based on results of use of health care and efficacy from a trial of
      zidovudine treatment. SETTING--Seven Veterans Affairs medical centres in the
      United States. SUBJECTS--338 patients with symptomatic HIV infection and a
      lymphocyte count of 200 x 10(6) to 500 x 10(6) CD4 cells/l. INTERVENTIONS-
      Zidovudine 1500 mg/day started either at recruitment to the trial or when CD4
      cell count fell below 200 x 10(6)/l. MAIN OUTCOME MEASURES--Health care costs and
      rates of disease progression between six clinical states of HIV infection.
      RESULTS--Patients given early treatment with zidovudine remained without AIDS for
      an extra two months at a cost of $10,750 for each extra month without AIDS (at
      1991 costs). Cost effectiveness ratio was most sensitive to the cost of
      zidovudine and to the quality of life of patients receiving early treatment. At
      treatment of 500 mg/day the cost effectiveness ratio for early treatment was
      $5432 for each extra month without AIDS. Patients given early treatment
      experienced more side effects, and if their quality of life was devalued by 8%
      compared with patients treated later the two treatments were equivalent in terms
      of quality adjusted months of life without AIDS. CONCLUSIONS--Early treatment
      with zidovudine is expensive and is very sensitive to the cost of zidovudine and
      to potential reductions in quality of life of patients who experience side
      effects. Doctors should reconsider early treatment with zidovudine for patients
      who experience side effects that substantially compromise their quality of life.

PMID- 8257888
TI  - High prevalence of asthma in cross country skiers.
AB  - OBJECTIVES: To study the prevalence of asthma (asthma symptoms and bronchial
      hyperresponsiveness) in Swedish cross country skiers compared with non-skiers and
      monitor changes in symptoms and bronchial hyperresponsiveness during the year.
      DESIGN: Cross sectional study during the winter ski season and in the summer.
      SETTING: Six ski clubs for elite skiers (total 47) in two different areas of
      Sweden. SUBJECTS: 42 elite cross country skiers and 29 non-skiing referents. MAIN
      OUTCOME MEASURES: Bronchial responsiveness, asthma symptoms, and lung function.
      RESULTS: Bronchial responsiveness was significantly greater and asthma symptoms
      more prevalent in the skiers than in the referents. There was no difference in
      bronchial responsiveness within either group between winter and summer. 15 of the
      42 skiers used antiasthmatic drugs regularly and 23 had a combination of asthma
      symptoms and hyperresponsive airways or physician diagnosed asthma, or both.
      Altogether 33 skiers had symptoms of asthma or bronchial hyperresponsiveness. One
      of the referents had symptoms of asthma and bronchial hyperresponsiveness, and
      none used antiasthmatic drugs regularly. CONCLUSIONS: Asthma, asthma-like
      symptoms, and bronchial hyperresponsiveness are much more common in cross country
      skiers than in the general population and non-skiers. Strenuous exercise at low
      temperatures entailing breathing large volumes of cold air is the most probable
      explanation of persistent asthma in skiers.

PMID- 8257889
TI  - Importance of placement of intra-articular steroid injections.

PMID- 8257890
TI  - Avoiding the pitfalls of sponsored multicentre research in general practice.
AB  - Research in general practice is becoming increasingly popular, and most general
      practitioners will sooner or later have to decide whether to become involved with
      clinical trials sponsored by drug companies. This paper outlines the advantages
      and disadvantages of multicentre research--based on experience of running a
      research group since the early 1980s--to enable doctors to reach the appropriate
      decision and to avoid involvement in trials which are either unethical or
      ineffective.

PMID- 8257891
TI  - Publishing the findings of clinical research.
AB  - Current regulations and practice may not prevent a sponsor of clinical research
      from delaying or preventing the dissemination of findings that do not support his
      or her commercial, professional, or managerial interests. Pharmaceutical trials
      are particularly subject to this concern, but the issue of non-publication has a
      wider significance. Patients participate in research on the understanding that it
      will be of public benefit. To be fair to these patients we must confirm that data
      will be analysed without bias and that findings will be regarded as being in the
      public domain and hence available to interested reviewers even if the results do
      not justify publication. Clinical investigators and ethics committees have the
      power and the duty to enforce this outcome.

PMID- 8257892
TI  - ABC of emergency radiology. The abdomen--I.

PMID- 8257893
TI  - Advanced techniques in abdominal surgery.
AB  - Almost every abdominal organ is now amenable to laparoscopic surgery.
      Laparoscopic appendicectomy is a routine procedure which also permits
      identification of other conditions initially confused with an inflamed appendix.
      However, assessment of appendiceal inflammation is more difficult. Almost all
      colonic procedures can be performed laparoscopically, at least partly, though
      resection for colonic cancer is still controversial. For simple patch repair of
      perforated duodenal ulcers laparoscopy is ideal, and inguinal groin hernia can be
      repaired satisfactorily with a patch of synthetic mesh. Many upper abdominal
      procedures, however, still take more time than the open operations. These
      techniques reduce postoperative pain and the incidence of wound infections and
      allow a much earlier return to normal activity compared with open surgery. They
      have also brought new disciplines: surgeons must learn different hand-eye
      coordination, meticulous haemostasis is needed to maintain picture quality, and
      delivery of specimens may be problematic. The widespread introduction of
      laparoscopic techniques has emphasised the need for adequate training (operations
      that were straight-forward open procedures may require considerable laparoscopic
      expertise) and has raised questions about trainee surgeons acquiring adequate
      experience of open procedures.

PMID- 8257894
TI  - The need for chaperones. Is greatest during intimate examination.

PMID- 8257895
TI  - Schistosomiasis in Malawi.

PMID- 8257896
TI  - Urination and fluid intake.

PMID- 8257897
TI  - Suspended doctors.

PMID- 8257898
TI  - Altered inflammatory responses in smokers.

PMID- 8257899
TI  - Care of suicidal prisoners.

PMID- 8257900
TI  - Performance indicators in general practice.

PMID- 8257901
TI  - Waiting list times for treatment.

PMID- 8257902
TI  - Natural family planning. Natural methods have cross cultural appeal.

PMID- 8257903
TI  - Natural family planning. Unplanned pregnancy rates declining.

PMID- 8257904
TI  - Natural family planning. Cheap, effective, and free of side effects.

PMID- 8257905
TI  - Natural family planning. ...and empowers couples.

PMID- 8257906
TI  - Natural family planning. The tide is turning in favour.

PMID- 8257907
TI  - Natural family planning. Both partners need instruction.

PMID- 8257908
TI  - Natural family planning. Attitudes against natural methods must change.

PMID- 8257909
TI  - Natural family planning. Demand is increasing.

PMID- 8257910
TI  - Natural family planning. Low failure rate with symptothermal method.

PMID- 8257911
TI  - Natural family planning. Advocates and detractors have different sexual
      philosophies.

PMID- 8257912
TI  - Natural family planning. Author's reply.

PMID- 8257913
TI  - Natural family planning. The family planning method of the future.

PMID- 8257914
TI  - Transcription control elements of the rat neuronal nicotinic acetylcholine
      receptor subunit alpha 3.
AB  - 1. In situ hybridization histochemistry has revealed that neuronal nicotinic
      acetylcholine receptor subunits are widely expressed in unique although
      overlapping patterns in the central and peripheral nervous systems. In addition,
      an intricate regulation of expression is apparent during development. This raises
      the question of the transcription control of these complex distributions. 2. An
      analysis of the transcription control elements of one nicotinic receptor subunit,
      alpha 3, which is expressed both in the central and peripheral nervous systems as
      well as in PC12 cells, is presented here. 3. Overlapping genomic clones
      containing the rat beta 4, alpha 3, and alpha 5 gene cluster were isolated and a
      restriction map of this region was constructed. 4. The transcription start sites
      of the alpha 3 gene were mapped by RNase protection experiments. Surprisingly,
      there is no consensus TATA box upstream of these sites. This is consistent with
      the finding of multiple initiation sites. 5. Functional assays were done in PC12
      cells using the bacterial chloramphenicol acetyltransferase gene as a reporter
      gene. Several restriction fragments from the region located 5' and including the
      transcription start sites were shown to promote transcription of the reporter
      gene and thus contain at least part of the alpha 3 promoter. In addition, a
      region further upstream, within the beta 4 transcription unit, appears to reduce
      transcriptional activity and thus could be a silencer. 6. It is proposed that
      this putative silencer is a selective force in maintaining the tight linkage of
      these three genes.

PMID- 8257915
TI  - Kinetic studies of nitrite uptake by Aspergillus nidulans.
AB  - 1. In the filamentous mold Aspergillus nidulans, net nitrite uptake is inducible
      by nitrate and nitrite, is probably different from the nitrate uptake system and
      is partially repressed by ammonium. 2. The concentration dependence of net
      nitrite uptake by the biA1 facA303 strain of A. nidulans shows a saturation
      kinetics with an apparent Km value of 0.64 mM. 3. Strains of A. nidulans carrying
      the nihA1 and nihA1 chlA14 mutations considerably reduced the affinity of the
      nitrite uptake system for the substrate when nitrite concentrations ranging from
      2.5 mM to 10.0 mM were tested (apparent Km values of 5.9 mM and 23.6 mM,
      respectively). 4. These results suggest that the toxic effect of nitrite on A.
      nidulans is due to enhanced nitrite uptake by nihA strains when high
      concentrations are present in the medium.

PMID- 8257916
TI  - Purification, physicochemical characterization and N-terminal-amino acid sequence
      of a phospholipase A2 from Bothrops jararaca venom.
AB  - Snake venoms usually contain multiple molecular forms of phospholipase A2 enzymes
      (phosphatide acyl hydrolase, E.C. 3.1.1.4; PLA2). Phospholipases A2 induce a wide
      range of pharmacological effects which may depend or not on the hydrolysis of
      phospholipids. In this study, a PLA2 from Bothrops jararaca venom was purified to
      homogeneity by gel filtration on a Sephacryl S-200 column, followed by FPLC
      reverse-phase chromatography on a Pep-RPC HR 5/5 column (yield 1.63% of venom
      protein). The PLA2 activity of the fractions was determined by indirect hemolysis
      using hen's egg yolk lecithin as substrate. The enzyme is an acidic protein with
      PI 4.5 and an apparent molecular weight of 14,200, as estimated by gel filtration
      on a Superose 12 FPLC column. Similar properties have been described for PLA2
      from other snake venoms. The N-terminal-sequence of the purified protein was
      NLMQFETMIMXXAGQ. These partial sequence data show a high degree of homology
      between the B. jararaca PLA2 and the enzymes from other snake venoms as well as
      bovine pancreatic PLA2.

PMID- 8257917
TI  - Heterogeneity of cysteine proteinases in Leishmania braziliensis and Leishmania
      major.
AB  - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with
      acrylamide copolymerized with gelatin (substrate-SDS-PAGE) was used to compare
      promastigote proteinases from two Leishmania species (L. braziliensis and L.
      major-like). Substrate-SDS-PAGE resolved at least 6 distinct proteinase
      activities with relative molecular masses between 20 and 65 kDa. The profile of
      proteinase activity was the same for both species, although qualitative
      differences were observed. L. major-like expressed a low molecular weight (20
      kDa) proteinase with maximum activity at pH 7.0, which was demonstrable from pH
      5.0 to pH 8.0. The 20-kDa protease was recovered in the detergent phase of TX-114
      and was inhibited by the sulfhydryl group-blocking reagent E-64 (2.5 mM) and the
      non-specific inhibitor iodoacetic acid (1 mM). Pepstatin (1 microM) and PMSF (2.5
      mM) did not inhibit the 20-kDa enzyme. The present study suggests that both
      Leishmania species studied express hydrophobic cysteine proteases of different
      molecular weights, since about 2 x 10(7) parasites were analyzed in each lane and
      the proteolytic activity developed at 37 degrees C for 16 h.

PMID- 8257918
TI  - Left ventricular mass estimated by M-mode echocardiogram is not altered by
      changes in cardiac shape and dimensions due to acute arterial hypertension.
AB  - The effect of changes in left ventricular (LV) shape and dimensions due to acute
      arterial hypertension induced by mechanical obstruction of the aorta for 10 min
      on LV mass values estimated by M-mode echocardiogram was studied in 14
      anesthetized dogs. Although the systolic pressure increased from 117.5 +/- 19.9
      to 175.4 +/- 22.9 mmHg altered ventricular diameter from 2.77 +/- 0.49 cm to 3.17
      +/- 0.67 cm (P < 0.05) and wall thickness from 0.83 +/- 0.09 to 0.75 +/- 0.09 cm
      (P < 0.05), LV mass estimated before (73.5 +/- 19.1 g) and after (78.3 +/- 26.4
      g) hypertension was not significantly different. We demonstrate here for the
      first time that changes in LV dimensions induced by acute arterial hypertension
      do not modify LV mass values estimated by the M-mode electrocardiogram method.

PMID- 8257919
TI  - Adrenal response to adrenocorticotropin hormone and HLA typing of subjects with
      different degrees of 21-hydroxylase deficiency.
AB  - 1. To evaluate different degrees of 21-hydroxylase (21-OH) deficiency we studied
      the 17-hydroxyprogesterone (17-OHP) and cortisol response to the
      adrenocorticotropin hormone (ACTH) stimulation test. In a study of 13 families we
      characterized the relatives of patients with classical 21-OH deficiency using HLA
      antigen typing and the ACTH test. The subjects were divided into five groups: 12
      patients with the classical form, 11 patients with the nonclassical form, 38
      heterozygotes, 6 normal homozygotes and 33 controls. 2. The 17
      hydroxyprogesterone response to ACTH (mean +/- SD) varied as follows according to
      the degree of 21-OH deficiency: 25442 +/- 15718 ng/dl for the classical group,
      4198 +/- 1637 ng/dl for the nonclassical group, 348 +/- 267 ng/dl for the
      heterozygotes, 127 +/- 81 ng/dl for normal homozygotes, and 164 +/- 120 ng/dl for
      the controls. Basal plasma cortisol did not differ among the five groups. The
      cortisol response to ACTH was not different among controls (30 +/- 8
      micrograms/dl), normal homozygotes (28 +/- 7 micrograms/dl) and heterozygotes
      (26.5 +/- 7 micrograms/dl). The cortisol response was decreased in the patient
      groups and was lower in the classical (14 +/- 10 micrograms/dl) than in the
      nonclassical group (20 +/- 4 micrograms/dl). 3. In most families (11/13), HLA
      typing was informative in identifying the 21-OH deficiency containing haplotype,
      which correlated with the hormonal profile. In two families there was no
      correlation between the HLA genotype and the clinical expression of 21-OH
      activity for two HLA identical pairs of siblings.

PMID- 8257920
TI  - Thoracic lymph node metastasis and carcinomatous lymphangitis after inoculation
      of Walker 256 tumor through the trachea.
AB  - 1. Experimental models of carcinomatous lymphangitis have not been described.
      This is an important clinical entity which usually results in the patients'
      death, although its natural history is still controversial. This study was
      undertaken to investigate whether the pattern of lung involvement after Walker
      256 tumor inoculation through the trachea is a good model of carcinomatous
      lymphangitis. 2. Fifty male Wistar rats were inoculated through the trachea with
      2.5 x 10(6) Walker 256 tumor cells and killed in groups of 5 animals each at 6 h
      and on days 1, 3, 7, 14, 21, 28, 35, 45, and 60 of the experiment. The lungs and
      thoracic lymph nodes were examined by light microscopy. 3. There were no tumors
      in the 25 animals killed before the 21st day of the experiment. The remaining 25
      rats were sacrificed after 3 weeks of the experiment; 52% of them displayed
      thoracic lymph node metastases, and 40% developed a mild carcinomatous
      lymphangitis. The lung involvement did not correlate with respiratory distress,
      tumor dissemination or additional histological abnormalities. 4. We conclude that
      invasion of the lung is possible after intratracheal tumor cell inoculation, and
      that spreading follows a lymphatic pattern. This finding establishes this
      approach as a viable experimental model of carcinomatous lymphangitis. New
      approaches to increase the intensity and frequency of lung involvement, as well
      as the development of respiratory distress should be pursued in order to improve
      the efficiency of this model.

PMID- 8257921
TI  - Fast growth of a Brazilian hepatitis A virus (HAF-203) in a primate cell line.
AB  - A hepatitis A virus (HAV, HAF-203) isolated in Brazil was submitted to 8 serial
      passages through fetal Rhesus kidney cells (FRhK-4). The kinetics of replication
      were monitored by enzyme immunoassay (EIA-HAVAg) and cDNA-RNA dot blot
      hybridization. The maximum level of RNA, which was observed 21 days post
      infection (p.i.) during the 3rd passage, when HAVAg was still undetectable by
      EIA, served as a basis to establish subsequent passages every 21 days p.i. This
      schedule of passage resulted in a progressive reduction of time between culture
      infection and HAVAg and RNA production, together with an enhancement in antigen
      titer content of cell lysates. During the 7th passage, maximum HAVAg and RNA
      levels were detected at 7 days. Fourteen days after the 8th passage, clear
      morphological modifications appeared, suggesting a good adaptation of HAF-203 to
      FRhK-4 cells. Obtaining a fast-growing Brazilian HAV is very important for the
      development of vaccines.

PMID- 8257922
TI  - In vitro granuloma modulation induced by immune complexes in human
      Schistosomiasis mansoni.
AB  - Immune complexes (IC) were isolated from sera of six chronic schistosomiasis
      patients in order to study the regulatory mechanisms of granulomatous
      hypersensitivity to Schistosoma mansoni egg antigens in vitro. Purified blood
      mononuclear cells (PBMC) from patients (N = 14) with active schistosome infection
      when treated with a pool of isolated IC were able to inhibit granulomatous
      hypersensitivity as determined in an in vitro model of granuloma formation. The
      suppressive effect of IC on granuloma index varied from 33% to 73%. Analysis of
      the in vitro proliferation of PBMC from individuals infected with S. mansoni on
      blastogenesis assay (N = 7) showed that isolated IC were able to induce a
      suppression degree on cell proliferation from 31% to 93%. Significant inhibition
      of the in vitro granuloma reaction continued to be present after treatment of
      PBMC with supernatant from IC treated chronic patient cells. These results
      demonstrate that circulating IC may down-regulate granulomatous hypersensitivity
      to S. mansoni eggs in patients with chronic intestinal schistosomiasis.

PMID- 8257923
TI  - Effect of cannabidiol on plasma prolactin, growth hormone and cortisol in human
      volunteers.
AB  - In the present study, we investigated the effects of cannabidiol (CBD) on plasma
      prolactin, growth hormone and cortisol of 11 normal volunteers who received
      placebo or CBD at the doses of 300 mg (N = 7) or 600 mg (N = 4), po, in a double
      blind manner during two experimental sessions separated by an interval of at
      least one week. The sessions were held in the morning and consisted of blood
      collection and application of self-evaluation scales before and after drug
      injection (-35 to 180 min). Hormonal measurements were performed by
      radioimmunoassay. Basal prolactin (11.5 +/- 4.3 ng/ml) and growth hormone (1.5 +/
      0.7 ng/ml) levels were unchanged after placebo and CBD. In contrast, plasma
      cortisol levels decreased significantly during the placebo sessions (basal
      measurement = 11.0 +/- 3.7 micrograms/dl; 120 min after placebo = 7.1 +/- 3.9
      micrograms/dl), in agreement with the normal circadian rhythm of this hormone.
      This decrease in cortisol levels was significantly attenuated after CBD (basal
      measurement = 10.5 +/- 4.9 micrograms/dl; 120 min after 300 mg CBD = 9.9 +/- 6.2
      micrograms/dl; 120 min after 600 mg CBD = 11.6 +/- 11.6 micrograms/dl). CBD was
      also found to have a sedative effect as determined by the self-evaluation scales.
      The present results suggest that CBD interferes with cortisol secretion.

PMID- 8257924
TI  - Effect of time on remnant glomerular function.
AB  - 1. Although hypertrophy and hyperfiltration have been identified in remnant
      nephrons, the time of their appearance and the relationship between them have not
      been established. In order to evaluate remnant glomerular hemodynamics over
      different periods of time, we studied Munich-Wistar rats 7, 30 and 60 days after
      5/6 renal mass ablation. 2. Kidney weight increased after 7 days, continued to
      increase after 30 days and decreased after 60 days. Glomerular filtration rate
      (GFR) and renal plasma flow decreased by 67% and 7 days, were 35% lower than
      normal after 30 days, and after 60 days presented the same values as after 7
      days. Single-nephron GFR and glomerular plasma flow increased slightly after 7
      days, were 118% higher than control after 30 days, and decreased after 60 days.
      Hydraulic glomerular capillary pressure tended to increase after 30 days (6%),
      reaching statistical significance after 60 days (45 vs 62 mmHg). The glomerular
      ultrafiltration coefficient increased significantly after 30 days (82%) and
      decreased to values similar to the control group after 60 days. 3. These data
      suggest that kidney hypertrophy occurs early after reduction of renal mass,
      before the hemodynamic adaptations are complete. Glomerular hypertension was
      observed after 60 days, when single-nephron GFR and the glomerular
      ultrafiltration coefficient were decreased compared to rats studied after 30
      days. 4. These data may indicate that, once glomerular hypertension starts,
      structural abnormalities are followed by a decline in glomerular function.

PMID- 8257925
TI  - Simian viruses, organ xenotransplantation and a hypothesis about the origin of
      AIDS.

PMID- 8257926
TI  - Pharmacological analysis of fear-potentiated startle.
AB  - 1. The potentiated startle paradigm measures conditioned fear by an increase in
      the amplitude of a simple reflex (the acoustic startle reflex) in the presence of
      a cue previously paired with shock. This paradigm offers a number of advantages
      as an alternative to most animal tests of fear or anxiety because it involves no
      operant and is reflected by an enhancement rather than a suppression of ongoing
      behavior. 2. A variety of drugs which block anxiety in people block fear
      potentiated startle in rats. Although the 5-HT1A agonist buspirone is especially
      effective in blocking fear-potentiated startle, more selective 5-HT1A agonists
      have been less consistently effective. However, when these drugs are combined
      with only partially effective doses of the D1 antagonist, SCH23390, a full
      blockade of fear-potentiated startle is achieved. Hence, synergistic actions
      appear to occur between serotonin and dopamine in modulating the expression of
      fear-potentiated startle. 3. In addition to pharmacological studies,
      physiological studies are being used to define the neural pathways necessary for
      a visual conditioned stimulus to alter the acoustic startle reflex. The current
      working hypothesis is that the conditioned stimulus activates the central nucleus
      of the amygdala through a pathway involving the lateral geniculate nucleus,
      perirhinal cortex, and lateral and basolateral amygdaloid nuclei. The central
      nucleus of the amygdala then projects directly to the acoustic startle pathway so
      as to modulate the startle response. Chemical or electrolytic lesions of either
      the central nucleus or the lateral and basolateral nuclei of the amygdala block
      the expression of fear-potentiated startle. These latter amygdaloid nuclei may
      actually be the site of plasticity for fear conditioning, because local infusion
      of the NMDA antagonist AP5 blocks the acquisition but not the expression of fear
      potentiated startle. 4. Finally, we have begun to investigate brain systems that
      might be involved in the inhibition of fear. Local infusion of AP5 into the
      amygdala was found to block the acquisition of experimental extinction, a
      prototypical method for reducing fear. We have also established a reliable
      procedure for producing conditioned inhibition of fear-potentiated startle and
      hope to eventually understand the neural systems involved in this phenomenon.

PMID- 8257927
TI  - Cloned genes of the aerobactin system of virulent avian Escherichia coli do not
      confer virulence to recombinant strains.
AB  - 1. We cloned the aerobactin region and its receptor from pMV14, a large
      nonconjugative plasmid isolated from the virulent strain UEL14, to assess the
      importance of the aerobactin iron uptake system as a virulence determinant in
      septicemic avian Escherichia coli. 2. The physical map of the region of the
      recombinant plasmid (pGMV1) containing the genes for synthesis of aerobactin and
      its receptor was very similar to the corresponding region in pABN1 containing the
      genetic determinants for the aerobactin system of pColV-K30. 3. The 74-kDa outer
      membrane protein encoded by pGMV1 cross-reacted immunologically with the 74-kDa
      aerobactin receptor protein encoded by pABN1. 4. Various avirulent E. coli
      strains carrying the recombinant plasmid, which contains only the aerobactin
      system, were assayed for virulence and were found to be avirulent for chickens.
      Only the wild-type aerobactin-producing strain was virulent in a pathogenicity
      test for chickens. 5. These results show that the aerobactin system by itself
      does not confer virulence, and that other factors are necessary for virulence of
      avian strains of E. coli.

PMID- 8257928
TI  - Steroid receptors in Brazilian patients with large bowel cancer.
AB  - 1. Twenty-two colorectal carcinomas were examined for the presence of estrogen
      (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a
      charcoal dextran assay. 2. ER was detected in 4/13 (31%) and 5/9 (56%) of the
      rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and
      from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa
      presented similar incidence and ER density values within the tumor ranges. 3. The
      incidence of PR-positive samples was also higher in colon than in rectal
      carcinomas (44% vs 23%). Normal mucosa displayed significantly higher PR titers
      than the corresponding tumor tissue. It seems reasonable to assume that normal
      colorectal mucosa may be one of the target tissues of progesterone activity. Most
      tumor biopsies and normal mucosa were completely AR negative, whilst GR was
      present in a larger fraction (63%) of tumoral specimens, occurring more commonly
      in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms
      than in normal mucosa (54% vs 38% in rectum and 78% vs 56% in colon), suggesting
      that glucocorticoids may be involved in the control of tumor-cell proliferation.
      4. Our findings which indicate low densities of ER, PR, and absence of AR in some
      large bowel cancers, suggest sex hormone and endocrine independence for those
      cancers. The role of glucocorticoid receptors in those forms of cancer remains to
      be elucidated.

PMID- 8257929
TI  - Mononuclear phagocytic system in acute pancreatitis.
AB  - 1. Functional alterations of the mononuclear phagocytic system (MPS) may be an
      important factor in the pathogenesis of infection in acute pancreatitis (AP). In
      the present study, MPS activity was investigated in rats and hepatic blood flow
      (HBF) was also determined. 2. A total of 122 male Wistar rats were divided into
      three groups: 1, AP group (N = 51); 2, sham-operated (SO) (N = 49); 3, intact
      group (IG) (N = 22). AP was induced by retrograde injection of 0.5 ml of 2.5%
      sodium taurocholate saline into the main biliopancreatic duct under ketamine
      chloride anesthesia. SO animals were submitted to the same surgical steps as AP
      animals except for AP induction. 3. Each experimental group was subdivided into
      two subgroups. The first subgroup was submitted to the study of MPS activity as
      follows: each group was injected with colloidal 198Au and liver clearance
      parameters were determined 2 h (N = 11), 12 h (N = 10) and 24 h (N = 10) later in
      the AP group, and 2 h (N = 9), 12 h (N = 10) and 24 h (N = 11) later in the SO
      group. In the second subgroup, HBF was assessed using 131I-bromosulphalein at 2 h
      (N = 10) and 24 h (N = 10) in the AP group and at 2 h (N = 10) and 24 h (N = 10)
      in the SO group. The IG was submitted to both radioactive tracer studies. Each
      animal was used for only one experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257930
TI  - Serum serotonin levels of normal and autistic children.
AB  - 1. Serum serotonin (5HT) was determined in normal and autistic children by high
      performance liquid chromatography with electrochemical detection (HPLC-ED), after
      serum deproteinization. 2. The sample deproteinization was carried out by the
      addition of 3.4 M HCLO4 to a small volume of the serum, followed by freezing,
      centrifugation, dilution and injection of sample into the HPLC. 3. Serum 5HT
      concentration was significantly increased in autistic children (303 +/- 92 ng/ml)
      (N = 19) when compared to that of normal children (215 +/- 67 ng/ml) (N = 46).
      The data of normal children analyzed by ANOVA for sex or age showed no
      difference. 4. The method employed in this study showed high resolution, good
      sensitivity and can be used for routine determination of serum 5HT in the
      clinical investigation of hyperserotonemia in autism.

PMID- 8257931
TI  - The diphenhydramine-induced decrease in general open-field activity of female
      rats is gonadal steroid dependent.
AB  - The effect of ovarian steroids on sedative effects of diphenhydramine (D), a
      histamine H1 receptor blocker, was determined. Seventy-five female Wistar rats
      were randomly divided into three groups: Group 1 (N = 54) was ovariectomized,
      group 2 (N = 7) was sham-operated, and group 3 (N = 14) was intact. The
      ovariectomized rats were then subdivided into 4 groups. Two groups received
      peanut oil 54 and 6 h before treatment with saline solution (group OS) or 20
      mg/kg D (group OD). The other two groups received 50 micrograms/kg 17-beta
      estradiol and 2 mg/kg progesterone, respectively, 54 and 6h before treatment with
      saline solution (group OHS) or 20 mg/kg D (group OHD). The sham-operated animals
      were treated as the OS group. Intact animals were injected with saline (group IS)
      or 20 mg/kg D (group ID) on the day of estrus, as determined by vaginal smears
      taken in the morning before the behavioral observations. Rats were observed for 6
      min in the open field during the dark period of the cycle, 15 min after the
      administration of saline or D. There was a similar decrease in locomotion and
      rearing frequencies in OHS vs OHD and IS vs ID groups. Nevertheless, a lack of D
      sedative effect was observed in OD rats (locomotion and rearing frequencies, 56.0
      +/- 3.3 vs 46.1 +/- 3.8 and 15.5 +/- 1.6 vs 15.2 +/- 1.6., for OS and OD groups,
      respectively). The results suggest that the sedative effect of diphenhydramine
      depends on the presence of ovarian steroids.

PMID- 8257932
TI  - 2-deoxyglucose-induced food intake by Nile tilapia, Oreochromis niloticus (L.).
AB  - The alimentary and glycemic responses to cytoglycopenia were studied in thirty
      one Nile tilapia alevins of indeterminate sex and age, measuring on average 10.67
      +/- 0.82 cm. The cytoglycopenia was provoked by ip injection of 60 mg/kg 2-deoxy
      D-glucose (2-DG, N = 16). The control group (N = 15) was submitted to ip
      injection of 0.2 ml saline. Blood samples for glucose determination were obtained
      before and three hours after drug administration by cardiac puncture. Food was
      then offered ad libitum. One hour later the animals were sacrificed and their
      stomachs removed. The difference in wet weight between full and empty stomach was
      utilized to quantify the food intake. Median food intake was 0.3877 g for the
      fish treated with 2-DG and 0.107 g for the animals injected with saline. This
      difference was statistically significant by the Mann-Whitney test (P < 0.05). The
      median values of blood glucose levels before drug injection were 46.19 mg/100 ml
      in the 2-DG-treated fish and 44.54 mg/100 ml in the control group. Three hours
      after drug administration, the values were 48.64 mg/100 ml in the experimental
      group and 56.90 mg/100 ml in the control group. The difference between the values
      of blood glucose before and after the drug was not significant for either group.
      We conclude that glucoprivation provokes food intake in fish and that the same
      glucoprivation was not sufficient to provoke hyperglycemia.

PMID- 8257933
TI  - Ca2+ transport and oxidative damage of mitochondria.
AB  - 1. Mitochondria from a wide range of sources have the ability to accumulate Ca2+
      down their electrochemical gradient mediated by a uniport mechanism. 2. Ca2+
      efflux occurs via two separate pathways: a Na+/Ca2+ exchanger that predominates
      in mitochondria from excitable tissues and a Na(+)-independent pathway that
      predominates in mitochondria from non-excitable tissues. 3. The kinetic
      characteristics of these calcium influx-efflux pathways appear to be incompatible
      with any role for mitochondria as cytosolic Ca2+ buffers, under resting normal
      physiological conditions. Instead, the biological role of this Ca(2+)
      transporting system seems to be the regulation of matrix Ca2+ in a range that
      permits the regulation of three intramitochondrial Ca(2+)-dependent
      dehydrogenases which catalyze rate-limiting reactions of the Krebs cycle. 4.
      Under conditions in which a high cytosolic Ca2+ concentration is sustained, the
      matrix Ca2+ concentration may attain levels that lead to impairment of
      mitochondrial functions such as inhibition of oxidative phosphorylation and
      increase in inner membrane permeability. 5. Accumulation of Ca2+ by mitochondria
      under conditions of oxidative stress induces an increase in inner membrane
      permeability by a mechanism that appears to be mediated by protein polymerization
      due to thiol cross-linking.

PMID- 8257934
TI  - Partial purification and some physicochemical properties of phospholipases A2
      from the venom of the bushmaster snake (Lachesis muta).
AB  - Screening of the biochemical-pharmacological properties of the crude venom from
      the snake Lachesis muta indicated the presence of phospholipase A2 (PLA2; 5260
      U/mg protein), procoagulant (2630 U/mg protein), platelet aggregating (43 U/mg
      protein) and caseinolytic activities (6670 U/mg protein). These activities were
      separated by filtration of the crude venom on Sephacryl S-200. The material
      containing PLA2 activity was further fractioned by DEAE-cellulose ion exchange
      chromatography into four active fractions (F-I to F-IV, containing 1.7, 1.2, 0.3,
      and 0.05% of the crude venom protein, respectively) by stepwise elution with
      buffers of increasing ionic strength. All fractions presented a molecular weight
      of approximately 15,000 and isoelectric points in the range pH 4.6-6.0. In
      addition to their indirect hemolytic activity, the partially purified fractions
      inhibited platelet aggregation induced either by collagen or thrombin. p
      Bromophenacyl bromide-treated fractions lost both phospholipase A2 activity and
      their inhibitory effect on collagen-induced platelet aggregation.

PMID- 8257935
TI  - Ca(2+)-dependent phosphorylation of the tail domain of myosin-V, a calmodulin
      binding myosin in vertebrate brain.
AB  - 1. Myosin-V from vertebrate brain is a novel molecular motor with a myosin-like
      head domain, a calmodulin-binding neck region and a unique tail domain of unknown
      function. Previous studies showed brain myosin-V to be a phosphoprotein substrate
      for Ca2+/calmodulin-dependent protein kinase associated with actomyosin. In the
      present study we describe the preparation of a specific actin-cytoskeletal
      fraction which is enriched in brain myosin-V. 2. We show that Ca2+/calmodulin
      dependent protein kinase activity is also associated with this preparation and
      phosphorylates brain myosin-V. 3. Calpain, a Ca(2+)-dependent protease, generates
      a M(r) 80,000 fragment from the COOH terminal region of brain myosin-V containing
      most or all of the phosphorylation sites. 4. These results suggest that the
      unique tail domain of this novel myosin is subject to Ca2+ control via
      phosphorylation by kinase activity associated with the actin cytoskeleton.

PMID- 8257936
TI  - Recovery of fibrinogen in cryoprecipitate pasteurized in the presence of sucrose
      and glycine.
AB  - The effect of sucrose (60% w/w) and 1 M glycine as thermal stabilizers for
      fibrinogen in cryoprecipitate was studied. Sucrose (9.2 g) and glycine (0.9 g)
      were dissolved in 6 g of cryoprecipitate and the solution was pasteurized at 60
      degrees C for 10 h. The preparation was then dialyzed for 20 h in phosphate
      buffered saline (PBS), lyophilized, stored for one week at -40 degrees C and
      resuspended in distilled water. The recovery of total proteins and fibrinogen in
      the final product averaged 66.4 +/- 4.1% and 43.8 +/- 6.4% of the initial
      contents, respectively (mean +/- SEM, N = 9). The pasteurization of
      cryoprecipitate in the presence of PBS (control experiments) produced extensive
      precipitation, which is characteristic of protein denaturation. Thus, this method
      partially protected fibrinogen and other proteins in cryoprecipitate from
      inactivation by prolonged exposure to heat during pasteurization.

PMID- 8257937
TI  - Antagonizing the hydroxyl ion free radical (HO.) does not abolish reperfusion
      ventricular fibrillation in anesthetized dogs.
AB  - 1. The hypothesis that the hydroxyl ion free radical, HO; derived from O2 plays a
      pivotal role in the development of reperfusion ventricular fibrillation was
      tested in 63 anesthetized mongrel dogs of either sex weighing 14 +/- 7 kg
      submitted to 90-min coronary occlusion followed by 60-min reperfusion. 2. OH. was
      blocked by the iron chelator deferoxamine (DF, 500 mg) and by dimethylthiourea
      (DMTU, 500 mg/kg), a HO. scavenger both given iv over 30 min before reperfusion.
      3. The frequency of reperfusion ventricular fibrillation was similar in all
      animals, i.e., 7/27 (26%) control dogs, 7/23 (30%) DF-treated dogs and 3/13 (23%)
      DMTU-treated dogs. Arterial pressure, heart rate and double product were not
      significantly different among the three groups during occlusion or reperfusion.
      The hemodynamic variables were also similar among dogs that fibrillated and those
      that did not. Likewise, extent of ischemic areas and necrosis was similar among
      the three experimental groups, with the control values being 34 +/- 4% and 14 +/-
      5%, respectively. 4. We conclude that OH. does not play a major role in the
      induction of reperfusion ventricular fibrillation in the anesthetized dog with
      ischemia/necrosis.

PMID- 8257938
TI  - Heterogenous insulin response to an oral glucose load by patients with the
      indeterminate clinical form of Chagas' disease.
AB  - This study was designed to investigate the behavior of serum glucose and insulin
      in response to an oral glucose load in chagasic patients with the indeterminate
      clinical form of the disease. Sixteen chagasic patients and 28 healthy control
      subjects were studied after an overnight fast and during 2 h after ingestion of
      100 g glucose. There were no significant differences in serum glucose levels
      before and 2 h after the glucose load between chagasic and control subjects.
      However, in 8 chagasic patients, the total area under the insulin curve was
      significantly lower (2976 +/- 448 microU ml-1 120 min-1) than in the control
      (10123 +/- 995 microU ml-1 120 min-1) and in the remaining chagasic patients
      (9220 +/- 826 microU ml-1 120 min-1). These results suggest that the
      hypoinsulinemia of this subgroup of chagasic patients may be secondary to reduced
      insulin secretion and/or to increased peripheral insulin sensitivity probably
      related to autonomic dysfunction.

PMID- 8257939
TI  - Participation of macrophages in chloramphenicol-potentiated carrageenin-induced
      peritonitis in rats.
AB  - 1. We investigated the possible potentiating effect of chloramphenicol succinate
      (30 mg/kg, every 12 h for 4 days, ip) on the response of polymorphonuclear
      neutrophils to carrageenin (150 micrograms, ip) or dextran (100 micrograms, ip)
      in the peritoneal cavity of male Wistar rats (180-230 g; N = 12 in each group).
      2. Chloramphenicol potentiated the cell migration induced by carrageenin (35%)
      but not that induced by dextran. Previous macrophage depletion in the peritoneal
      cavity by washing with sterile saline abolished the cell response, whereas a
      previous thioglycollate-induced increase in macrophage numbers enhanced the
      potentiating effect (60%). 3. These results suggest that the potentiating effect
      on polymorphonuclear neutrophil migration induced by chloramphenicol may be
      related to chemotactic factors released by macrophages.

PMID- 8257940
TI  - Mouse hepatitis virus 3 and interferon gamma binding to extracted macrophage
      proteins correlate with virus growth in A/J and BALB/c mice.
AB  - 1. After immunization, adult A/J mice are resistant and BALB/c mice are
      susceptible to MHV3 infection. After IFN gamma activation, only macrophages
      originating from A/J mice were able to partially restrict MHV3 growth. 2. When
      the binding of MHV3 and interferon (IFN) gamma to solubilized cytoplasmic and
      membrane macrophage proteins of mice was determined by ELISA, there was more
      binding of MHV3 to proteins extracted from BALB/c macrophages than to proteins
      extracted from A/J macrophages. When the proteins were obtained from IFN gamma
      activated macrophages, decreased MHV3 binding was observed only in proteins
      originating from A/J macrophages. 3. ELISA showed a comparable binding of IFN
      gamma to A/J or BALB/c macrophage proteins. When the proteins were obtained from
      IFN gamma-activated macrophages, only IFN gamma-binding to A/J macrophage
      proteins was increased. 4. The results indicate a different expression and IFN
      gamma modulation of MHV3 receptors in macrophages from A/J and BALB/c mice, which
      directly correlated with their acquired resistance or susceptibility to MHV3
      infection.

PMID- 8257941
TI  - Effect of beta-myrcene on pentobarbital sleeping time.
AB  - Evidence that beta-myrcene (MYR) interferes with the metabolic activation of
      premutagens has been provided by in vitro studies. In order to determine whether
      MYR also interferes with the in vivo metabolism of xenobiotics, thereby modifying
      pharmacological responses to drugs, we investigated the effects of this
      monoterpene on pentobarbital (PT) sleeping time in rats. Two experiments were
      carried out. In the first, a single dose of MYR (0.25, 0.5 or 1.0 g/kg po) was
      given 1 h before PT (40 mg/kg ip). No effect was observed with the two lowest
      doses, but the highest MYR dose given 1 h before PT increased the PT-induced
      sleeping time (131 +/- 15 min vs 64 +/- 15 min for controls, mean +/- SD). In the
      second experiment, male rats were treated with MYR (1.0 g/kg po once a day) for
      14 days and injected with PT (40 mg/kg ip) 24 h after the last dose of MYR.
      Repeated treatment with MYR markedly reduced PT sleeping time compared to the
      vehicle-treated control group (21 +/- 13 min vs 35 +/- 19 min for controls, mean
      +/- SD). These results indicate that MYR interferes with the in vivo barbiturate
      metabolism and support the view that MYR induces the phenobarbital-inducible
      cytochrome P-450 (P-450 2B subfamily) enzymes in the rat.

PMID- 8257942
TI  - Effects of deltamethrin on the growth and differentiation of bone marrow
      hematopoietic stem cells.
AB  - 1. The effects of deltamethrin on mouse bone marrow and spleen progenitor cell
      responsiveness to granulocyte and macrophage colony-stimulating factors (CSFs)
      were evaluated. 2. Deltamethrin (1-5 mg/kg) was administered four times
      subcutaneously on alternate days for one week to male BALB/c mice, 5-8 weeks old
      (N = 6 mice/group), raised under pathogen-free conditions and maintained in
      conventional animal rooms for four weeks before use. Soft agar colony formation
      (CFU-C), marrow and spleen cell counts as well as body, spleen and thymus weights
      were determined. 3. Although treatment with the lowest dose (1 mg kg-1 48 h-1)
      produced no significant effect on CFU-C, the administration of 3 and 5 mg kg-1 48
      h-1 caused a more than two-fold increase in the formation of granulocyte and
      macrophage colonies in the marrow, but not in the spleen (control value = 100.5
      +/- 12 for N = 6). Colony numbers returned to normal values within five days
      after the end of deltamethrin administration. 4. No changes were observed in the
      total (range: 1-3 x 10(8) per spleen) and differential marrow and spleen cell
      counts, nor was there any alteration in spleen weight. However, treatment with
      the three doses resulted in a dramatic reduction in thymus weight. 5. These
      effects were not due to the liberation of endotoxin, because if endotoxin had
      been present it would have been < 0.060 ng/ml, a concentration that would not
      have a biological effect. 6. In vitro addition of 0.10 to 10 microM deltamethrin
      to marrow cell cultures obtained from untreated mice did not induce any response.
      7. These data indicate that the CSF-driven granulocyte and macrophage development
      provides a useful model for the study of the effects of toxicants on
      myelopoiesis.

PMID- 8257943
TI  - Biophysical properties of the human cardiac gap junction channel.
AB  - 1. Gap junction channels interconnect cells of the pacemaking, conduction and
      contraction elements of the heart and also endothelial and smooth muscle cells of
      vasculature, thereby providing pathways for electrotonic current spread and for
      second messenger diffusion. The major gap junction protein in the cardiovascular
      system is connexin43. 2. When human connexin43 is stably expressed in pairs of a
      communication-deficient cell line (SKHep1) channels are produced with unitary
      conductance (gamma j), lipophile sensitivity and voltage-dependent gating similar
      to those of mammalian systems in which connexin43 is endogenously expressed. 3.
      At moderate transjunctional voltages (Vj), two gamma j values dominated the
      recordings, about 60 and 90 pS with CsCl patch solution. The smaller channel size
      is favored by phosphorylating treatments and the larger channel, by
      dephosphorylating treatments. 4. Human connexin43 mutants truncated at the
      carboxy termini display a change in gamma j while a point mutation in the third
      transmembrane spanning domain appears to change channel selectivity. 5. Voltage
      dependence of the human connexin43 channel is marked at Vjs, above +/- 50 mV, but
      large residual conductance remains (due probably to a voltage-insensitive
      substate) even at the largest Vj values; kinetic but not steady-state behavior is
      affected by phosphorylation state.

PMID- 8257944
TI  - Lipid effects on nicotinic acetylcholine receptor gating and kinetics: a
      structural-functional correlation.
AB  - The nicotinic acetylcholine receptor (AChR) is still the paradigm of rapid ligand
      gated ion channels. Since the early finding of a motionally restricted shell of
      lipids ("annulus") in the immediate perimeter of the membrane-bound AChR,
      experimental evidence has supported the notion that the interface between the
      protein moiety and the adjacent lipid molecules is the site of action of a
      variety of pharmacologically relevant substances, including non-competitive
      inhibitors of the cholinergic system like some local anesthetics, short-chain
      alcohols, and steroids. Patch-clamp data on cells expressing the AChR protein add
      another dimension to this knowledge, enabling correlations to be established
      between the chemical composition of lipid-modified cells and the functional
      properties (ligand binding, channel gating) of the receptor protein in situ.

PMID- 8257945
TI  - Characteristics of arterial hypertension in response to bolus injection of
      phenylephrine in atropinized patients.
AB  - The changes of arterial pressure promoted by bolus injection of 50 micrograms
      phenylephrine (PHE) were studied in 20 atropinized patients (5 normal subjects,
      13 patients with mitral valve disease, 1 patient with essential arterial
      hypertension and 1 patient with hypertrophic cardiomyopathy) submitted to routine
      catheterism. Patients with aortic valve disease, left ventricular outflow tract
      obstruction and intracardiac shunt were excluded from the study. All patients
      were in sinus rhythm, without heart failure. Arterial pressure started to
      increase at 14.8 +/- 5.4 s (range, 5.6 to 27 s; mean +/- SD) after PHE. There was
      an increase of 37.8 +/- 16.7 mmHg (range, 12.5 to 70 mmHg) in systolic pressure
      and of 26.6 +/- 11.1 mmHg (range, 7.5 to 42.5 mmHg) in diastolic pressure. Peak
      hypertension was attained at 36.6 +/- 16.4 s (range, 10.8 to 64.9 s) and
      hypertension continued for 176 +/- 92 s (range, 11 to 365 s). Heart rate was 114
      +/- 21 bpm before PHE and 111 +/- 21 bpm (P < 0.05) after PHE. There were no
      adverse events associated with intravenous PHE injection in any patient, in
      accordance with the general view that bolus injection of PHE is a safe and
      practical maneuver to promote arterial hypertension.

PMID- 8257946
TI  - Human giant cell formation induced in vitro by Schistosoma mansoni antigens.
AB  - Although multinucleated giant cells have been described for many years in
      association with different chronic inflammatory responses, their participation in
      immunoregulatory mechanisms within the schistosome egg granulomas remains to be
      clarified. In this study we determined if soluble egg antigen (SEA) or adult worm
      antigen preparations (SWAP) from S. mansoni induce giant cell formation in vitro
      and their relationship with the intensity of granulomatous reactivity. Antigenic
      stimulation of peripheral blood mononuclear cells (PBMC) from patients (N = 9)
      with active schistosomiasis infection increased giant cell formation per field
      after the 12th day in culture when treated with S. mansoni SEA conjugated to
      polyacrylamide beads (PB-SEA) (17 +/- 1.2) and SWAP (PB-SWAP) (18.5 +/- 1.5). The
      increase in the number of giant cells was statistically significant when compared
      to the control polyacrylamide beads (PB) (9 +/- 1.1) and purified protein
      derivative conjugated to beads (PB-PPD) (11.6 +/- 1.7). We also observed a
      correlation between an increase in the number of giant cells and a decrease in in
      vitro granuloma index (GI) to PB-SEA (GI decreased from 4.3 +/- 0.2 on the 6th
      day to 3.2 +/- 0.2 on the 12th day) and PB-SWAP (GI decreased from 4.8 +/- 0.3 on
      the 6th day to 3.5 +/- 0.05 on the 12th day). These data suggest that giant cell
      formation may be one of the immunoregulatory mechanisms involved in the down
      regulation of the granuloma reaction against S. mansoni eggs.

PMID- 8257947
TI  - Influence of stimulus preexposure and of context familiarity on conditioned
      freezing behavior.
AB  - 1. This paper reports an experiment examining the influence of context on latent
      inhibition using conditioned freezing behavior as an index. 2. Two groups of 8
      Wistar rats (290-320 g) were placed in one chamber (Context 2) and either exposed
      7 times or not to a sound stimulus (68 dB, 90 s). Two additional groups of 8 rats
      received the same stimulation in a different environment (Context 1). Next, each
      rat was required to form a sound-shock (0.2 mA, 1.5 s) association (20 trials) in
      Context 2. Freezing behavior was measured both during sound (CS) presentation and
      during an equal period of time immediately preceding the CS. 3. When the test
      environment was familiar, the conditioning of fear was greater in the non
      preexposed than in the CS-preexposed group. Acquisition of conditioned freezing
      was intermediate when the test environment was unfamiliar, irrespective of CS
      preexposure. 4. These results further support the context specificity of latent
      inhibition. In addition, they suggest that novelty interferes with sound-shock
      associations.

PMID- 8257948
TI  - Role of the rostral ventrolateral medulla in the pressor response to stimulation
      of the nucleus raphe obscurus.
AB  - 1. Electrical stimulation of the nucleus raphe obscurus (NRO) in urethane
      anesthetized rats increases arterial blood pressure (BP) between 20 and 95 mmHg
      (mean, 61.14 +/- 6.57; N = 30). 2. Unilateral electrolytic destruction of the
      rostral ventrolateral medulla (RVLM) did not reduce BP or heart rate (HR) but
      significantly reduced the pressor response to NRO stimulation (control, delta
      76.0 +/- 5.4 mmHg; after lesion, delta 26.0 +/- 13.9 mmHg; P < 0.01, N = 5). 3.
      Bilateral destruction of the RVLM reduced basal BP (control, 104.1 +/- 11.4 mmHg;
      after lesion, 58.0 +/- 5.7 mmHg; P < 0.01) and the pressor response to NRO
      stimulation (control, delta 71.6 +/- 7.3; after lesion, delta 12.5 +/- 3.8 mmHg;
      P < 0.01, N = 6). 4. When topically applied to or microinjected into the RVLM,
      pentobarbital sodium (200 nl/1 microliters, 10 nmol) decreased BP, HR and the
      pressor response to NRO stimulation (control, delta 56.2 +/- 6.7 mmHg; after
      pentobarbital, delta 11.2 +/- 3.1 mmHg; P < 0.01, N = 13). Similar effects were
      obtained when glycine (200 nl, 50 nmol) was microinjected into RVLM (control,
      delta 40.5 +/- 5.9 mmHg; after glycine, delta 18.1 +/- 4.9 mmHg; P < 0.01, N =
      6). 5. We conclude that RVLM is essential for the pressor response to NRO
      stimulation.

PMID- 8257949
TI  - Nephrotoxicity of human Bence Jones protein in rats: proteinuria and enzymuria
      profile.
AB  - The effect of intravenous administration of 80 mg purified human Bence Jones
      protein twice weekly for 5 weeks was investigated in male Wistar rats (N = 7; 2
      months old). A state of immunological tolerance was demonstrated by the absence
      of a B-cell response (plaque-forming cells and hemagglutination titers) and by
      the absence of detectable antigen or antibody deposition in glomeruli, as
      indicated by light and electron microscopy. No rise in blood urea level was
      detected (33.9 +/- 4.3 vs 32.8 +/- 1.3 mg%). There was an increase in proteinuria
      (5.3 +/- 0.9 vs 32.8 +/- 4.0 mg/day), mainly due to Bence Jones protein excretion
      (0 vs 29.2 +/- 5.2 mg/day), with a slight but significant increase in albuminuria
      (0.2 +/- 0.1 vs 1.0 +/- 0.2 mg/day). There was a significant increase of
      lysosomal N-acetyl-beta-D-glucosaminidase in the urine (6.1 +/- 1.3 vs 72.7 +/-
      18.8 mU/mg in creatinine). Lysosomal accumulation of Bence Jones protein in
      proximal tubular cells was evidenced by immunoelectronmicroscopy with protein A
      gold. These results clearly showed proximal tubular dysfunction induced by
      chronic Bence Jones protein administration, without interference of autologous
      immune response as demonstrated by immunological state of tolerance.

PMID- 8257950
TI  - Prepubertal development of rat prostate and seminal vesicle following chemical
      sympathectomy with guanethidine.
AB  - 1. The internal genital organs of prepubertal, 21-day old male Wistar rats were
      sympathectomized by ip injection of guanethidine (G), at doses of 5 mg/kg per day
      (N = 10) or 10 mg/kg per day (N = 10), for 20 days. Controls (N = 10) received
      saline. 2. Plasma testosterone level (measured by radioimmunoassay) decreased
      significantly in sympathectomized rats from 4.11 +/- 0.57 to 1.76 +/- 0.37 ng/ml
      (5 mg/kg G) and to 1.17 +/- 0.26 ng/ml (10 mg/kg G). Plasma levels of luteinizing
      and follicle-stimulating hormones and of prolactin were unaltered. 3. Chemical
      denervation caused a significant decrease in ventral prostate wet weight from
      74.3 +/- 5.5 to 59.3 +/- 4.7 mg (5 mg/kg G) and to 54.6 +/- 4.1 mg (10 mg/kg G)
      and in seminal vesicle wet weight from 36.5 +/- 6.8 to 31.7 +/- 5.2 mg (5 mg/kg
      G) and to 21.3 +/- 1.6 mg (10 mg/kg G). 4. The potential secretory activity of
      the prostate (measured in terms of fructose content) decreased significantly in
      guanethidine-treated rats from 0.38 +/- 0.02 to 0.30 +/- 0.02 mg/g (5 mg/kg G)
      and to 0.20 +/- 0.02 mg/g (10 mg/kg G). The seminal vesicle fructose content
      (0.33 +/- 0.04 mg/g for controls), however, was not altered by chemical
      denervation. 5. Our data suggested that sympathetic neurons may be involved in
      the control of LH receptors, at least in the prepubertal phase of sexual
      development. They may also be directly related to growth and secretory activity
      of the male accessory sex glands.

PMID- 8257951
TI  - Gastric emptying of a liquid meal in experimental chemical pneumonitis.
AB  - Gastric emptying of a liquid test meal was studied in an experimental model of
      chemical pneumonitis. In the first phase, 160 microliters of a hydrocarbon
      mixture was injected iv into 10 young adult rats, and the same volume of saline
      solution was injected into 10 controls. Arterial blood gases and lung dry and wet
      weight were determined. In the second phase, gastric emptying of a 5% (w/v)
      glucose solution marked with phenol red (6 mg/dl) was studied 5, 10, 20 and 30
      min after orogastric infusion of the test meal. Gastric retention was determined
      by measuring the concentration of the marker in the residual test meal recovered
      from the stomach after killing the animal. Thirty-two experimental and 32 control
      animals were paired and eight pairs were used at each time. The wet weight and
      external volume of the lungs were determined in all animals and 20 experimental
      animals were analyzed histopathologically. The animals of the experimental group
      developed intense macro- and microscopic pulmonary alterations. PaO2 values (mean
      +/- SD) at the first (70.7 +/- 5.9 mmHg) and fifth hour (71.1 +/- 8.5 mmHg) were
      significantly lower than the respective values obtained for the control group
      (109.5 +/- 13.5 and 113.9 +/- 11.2 mmHg). Gastric retention at 5, 10, 20 and 30
      min was significantly higher in animals with pneumonitis (median: 59.1%, 55.4%,
      45.3%, 27.2%) when compared to respective values for the control group (median:
      47.5%, 46.6%, 24.1%, 19.3%). These results indicate a delay in the gastric
      emptying of liquids in serious pulmonary disorders.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8257952
TI  - Effect of sex hormones on gentamicin-induced nephrotoxicity in rats.
AB  - 1. There is clinical and experimental evidence that females are more susceptible
      to gentamicin-induced nephrotoxicity. To assess the role of sex as a risk factor
      in aminoglycoside-related acute renal failure 16 groups of five 120 +/- 15-day
      old (young adult) Wistar rats of both sexes, castrated and non-castrated, were
      treated with gentamicin. These rats were medicated with 40 mg kg-1 24 h-1
      gentamicin alone for 10 days. Some animals received gentamicin after 5 days of
      treatment with depot testosterone or estrogens. 2. Blood urea and creatinine
      levels before and after gentamicin administration were measured to evaluate renal
      function. Histological lesions were studied by light microscopy by two
      pathologists who were unaware of the group. Rats with normal or elevated levels
      of estrogens showed functional impairment after gentamicin. A poor correlation
      was detected between levels of urea/creatinine and histopathological findings. 3.
      Lesions were considerably more severe in females. Testosterone administration to
      intact animals offered partial protection against the renal effects of gentamicin
      in both sexes. In contrast, estradiol administered to intact animals was
      regularly associated with significantly more severe lesions in both males and
      females. Castration by itself attenuated the gentamicin-induced renal alterations
      in males, but not in females. These data provide support for an unfavorable
      effect of estrogens rather than a favorable effect of testosterone. The
      demonstration of more severe lesions in female castrated rats when compared with
      male castrated rats indicates the participation of other factors, possibly of a
      genetic nature, in the pathogenesis of gentamicin-induced renal lesions.

PMID- 8257953
TI  - Does antisense make sense?

PMID- 8257954
TI  - Terfenadine: a mixture of equipotent antihistamine enantiomers without a clear
      'isomeric ballast'.
AB  - Terfenadine was the first non-sedating histamine H1 receptor antagonist and one
      of the most frequently prescribed H1 antihistamines. Terfenadine has one
      asymmetric centre in the molecule and is currently used as a racemate. Different
      methods and approaches for obtaining pure enantiomers of terfenadine are
      summarized and discussed in the present paper. Studies on antihistamine activity
      of the enantiomers, their side-effects on the central nervous system, calcium
      channel affinity and metabolism are also reviewed and analysed.

PMID- 8257955
TI  - Poisoning in children.
AB  - Drug-induced poisoning of children represents a serious medical as well as a
      social problem linked both to the fields of prevention and therapy. This paper
      analyses the occurrence and the causative agents of poisoning cases of children
      under the age of 15, hospitalized in a children's hospital over a two-year period
      (1985-1986). 33 Poisoning cases represented 1.7% of all hospitalizations, and 49%
      thereof were induced by drugs.

PMID- 8257956
TI  - Interindividual variation in the capacity-limited renal glucuronidation of
      probenecid by humans.
AB  - A dose of 1,000 mg probenecid was administered orally to 14 human volunteers in
      order to quantify the maximal rate of formation and excretion of probenecid acyl
      glucuronide in the urine. Probenecid showed dose-dependent pharmacokinetics.
      Plasma protein binding of probenecid was high, being somewhat higher in males
      (90.7 +/- 1.4%) than in females (87.9 +/- 1.4%; p = 0.0019). It was shown that
      probenecid is metabolized by cytochrome P-450 into at least two phase I
      metabolites. Each of the metabolites accounted for less than 12% of the dose
      administered; the main metabolite probenecid acyl glucuronide, representing 42.9
      +/- 13.2% of the dose, was only present in urine and not in plasma. The renal
      excretion rate-time profile of probenecid acyl glucuronide showed a plateau value
      in the presence of an acidic urine pH. This plateau value was maintained for
      about 10 h at the dose of 1,000 mg. The height of the plateau value depended on
      the individual and varied between 250 and 800 micrograms/min (15-50 mg/h). It was
      inferred that probenecid acyl glucuronide is formed in the kidney during blood-to
      lumen passage through the tubular cells. We conclude that the plateau value in
      the renal excretion rate of probenecid glucuronide reflects its Vmax of
      formation.

PMID- 8257957
TI  - A prospective analysis of risk factors for the discontinuation of second-line
      antirheumatic drugs.
AB  - Clinical and laboratory factors influencing the discontinuation of second-line
      antirheumatic drugs were prospectively studied using survival analysis in a
      consecutive series of 245 patients with recently diagnosed rheumatoid arthritis.
      A statistically significant influence of age, sex, serum IgA and HLA-DR3 on the
      discontinuation rate of chrysotherapy because of toxicity was observed. The
      discontinuation of sulfasalazine was increased by advanced age and high rank
      order of prescription. With respect to efficacy, high initial disease activity
      appeared to predispose to treatment termination of hydroxychloroquine,
      sulfasalazine and penicillamine. Furthermore, an influence of the rank order of
      prescription on discontinuation of sulfasalazine therapy because of lack of
      efficacy was found. Of interest is that discontinuation of hydroxychloroquine
      therapy because of lack of efficacy occurred less frequently in HLA-DR3-positive
      than in HLA-DR3-negative patients. Although these prognostic factors are of
      secondary importance in clinical practice, they may be of significance in the
      interpretation and comparison of clinical trials.

PMID- 8257958
TI  - Public health problems and the rapid estimation of the size of the population at
      risk. Torsades de pointes and the use of terfenadine and astemizole in The
      Netherlands.
AB  - Recently, the use of astemizole and terfenadine, both non-sedating H1
      antihistamines, caused considerable concern. Several case reports suggested an
      association of both drugs with an increased risk of torsades de pointes, a
      special form of ventricular tachycardia. The increased risk of both H1
      antihistamines was associated with exposure to supratherapeutic doses; for
      terfenadine the risk was also associated with concomitant exposure to the
      cytochrome P-450 inhibitors ketoconazole, erythromycin and cimetidine. To predict
      the size of the population that runs the risk of developing this potentially
      fatal adverse reaction in the Netherlands, the prevalence of prescribing
      supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome
      P-450 inhibitors was studied. Data were obtained from the PHARMO data base in
      1990, a pharmacy-based record linkage system encompassing a catchment population
      of 300,000 individuals. The results of the study showed that the prescribing of
      supratherapeutic doses and the concomitant exposure to terfenadine and cytochrome
      P-450 inhibitors was low. Furthermore, the results of a sensitivity analysis
      showed that the risk of fatal torsades de pointes has to be as high as 1 in
      10,000 to cause one death in the Netherlands in one year.

PMID- 8257959
TI  - Decision analysis applied to the selection of angiotensin-converting enzyme
      inhibitors.
AB  - Decision analysis is applied to the group of angiotensin-converting enzyme
      inhibitors, in order to select those which should be included in the hospital
      formulary and to establish a research method which allows the reproduction of the
      process with new, related drugs. Captopril, enalapril and lisinopril were the
      alternatives considered. Evaluation criteria were efficacy, clinical experience,
      safety, dosage interval, hepatic bioactivation, interactions, dosage forms and
      cost. A relative weight was assigned through a survey among the hospital's staff.
      Each alternative was evaluated in relation to all criteria. Sensitivity analysis
      was applied to validate the method. Enalapril obtained the highest score,
      followed by lisinopril and captopril. The sensitivity analysis confirms this
      result. Enalapril is selected for the hospital formulary due to its higher score,
      although the differences between the three are very small.

PMID- 8257961
TI  - The antiproteinuric effect of ACE inhibition in renal disease.

PMID- 8257960
TI  - Slow replenishment of carnitine deficiency after cessation of long-term treatment
      with pivaloyl-containing antibiotics.
AB  - Long-term treatment with pivampicillin and pivmecillinam for 6-24 months in five
      adults and one child reduced the total serum carnitine concentration to 3.7-14
      mumol/l (reference value: 25-66 mumol/l). Muscle carnitine was reduced to 0.3-0.7
      mumol/g wet weight (reference value: 3-5 mumol/g) in two cases. All patients had
      muscle symptoms with weakness, asthenia and pains. One showed signs of carnitine
      depletion in the liver with increased secretion of dicarboxylic acids (C6, C8,
      C10) in urine and limited ketone body formation during prolonged fasting. Serum
      carnitine increased slowly after cessation of therapy and reached normal
      concentrations after 6-12 months. All symptoms caused by carnitine depletion
      disappeared. This was achieved on a normal diet without carnitine
      supplementation.

PMID- 8257962
TI  - In-target production of [13N]ammonia: target design, products, and operating
      parameters.
AB  - [13N]Ammonia, commonly used in PET, has been prepared in good yield in the
      target. Up to 800 mCi of radiopharmaceutical was obtained by in-line processing
      of the irradiated water. Relatively low hydrogen pressure was used to control the
      target chemistry. Target designs and the product dependence on beam dose, dose
      rate and pressure are reported. Ethanol as a target additive was also
      investigated. Hydrogen and ethanol together were more effective than either alone
      at high beam dose. Parameters are reported for production needs from single doses
      to synthetic applications. An incidental method for production of [13N]nitrogen
      gas is also reported.

PMID- 8257963
TI  - Radiosynthesis of 6-[C-11]-D-glucose.
AB  - Availability of 6-[C-11]-D-glucose will permit positron emission tomography (PET)
      investigations of glucose utilization derived from the pentose shunt which
      supports biosynthesis in tissues. The first radiosynthesis of 6-[C-11]-D-glucose
      is described. As much as 1 mCi of 6-[C-11]-D-glucose, sufficient for animal
      studies, is obtained from [C-11]CO2 after 100 min with a 16% radiochemical yield
      (EOB). The radiosynthesis has many attractive features. The method uses [C
      11]CH3I and combines a Wittig reaction and a stereoselective OsO4 catalyzed
      alkene hydroxylation. The OsO4 hydroxylation of the [C-11]-labeled alkene (9) is
      accomplished in less than 10 min with high stereoselectivity (94:6) in favor of
      the 6-[C-11]-D-gluco-isomer. HPLC purification (C-18) of the protected labeled
      sugar removes the undesired 6-[C-11]-L-ido-sugar at an early stage and avoids the
      use of an expensive low-capacity ion-exchange HPLC column. OsO4, a highly toxic
      reagent, is removed in the process by adsorption and inactivation on polymer
      bound triphenylphosphine.

PMID- 8257964
TI  - Impurities in the [18O]water target and their effect on the yield of an aromatic
      displacement reaction with [18F]fluoride.
AB  - Fluorine-18 in the form of fluoride ion has widespread utility in PET
      radiochemistry. This paper explores the effect of possible metal ion
      contamination of the water on the yield of the displacement of a nitro group off
      of dinitrobenzene by fluoride has been investigated as a model reaction for
      fluoride displacement. The metal ions were found to have a profound effect if
      they were at the level of the carbonate added to the synthetic procedure. The
      yields from the reaction are best fit by a model in which the metal ions complex
      the carbonate ion and thus reduce the pH which in turn reduces the efficiency of
      the reaction. The formation of [18F]fluoroacetate in the target was explored as a
      mode for making the fluoride in the target unreactive. It was found that
      essentially no fluoroacetate was formed under our irradiation conditions. The
      sources of carrier fluoride were examined. It was found that carrier fluoride was
      introduced during the transfer of water into and out of the target and not during
      the irradiation.

PMID- 8257965
TI  - 205Bi/206Bi cyclotron production from Pb-isotopes for absorption studies in
      humans.
AB  - Pb(p, xn) thick target excitation functions were measured in the energy range 10
      38 MeV in order to optimize the production of isotopically pure radiobismuth from
      natPb, 206Pb, and 207Pb. Additionally, the decay of Po-isotopes from deuteron
      irradiation of natural bismuth (209Bi) was exploited for radiobismuth production.
      205Bi was produced from 206Pb at 20 MeV with only 2% of 206Bi at 4 weeks post
      irradiation. Bismuth compounds as used in the treatment of peptic ulcer were
      labeled with 205Bi for absorption studies in animals and subjects.

PMID- 8257967
TI  - Lung transplantation.

PMID- 8257966
TI  - Survey of 237Np and plutonium isotopes in principal foodstuffs in China.

PMID- 8257968
TI  - Industrial solvents--a cause for concern?

PMID- 8257969
TI  - Cardiopulmonary intermediate intensive unit: time course of two years activity.
AB  - Intermediate intensive care may be defined as a post comprehensive programme,
      where monitoring, combined with necessary treatment, improves and maintains
      physiological functions to complete the cure of underlying diseases. The aims of
      this paper are: 1) to describe the caring activity that patients admitted to our
      12 bed Cardiopulmonary Intermediate Intensive Unit (CPIIU) experience and, 2) to
      demonstrate that a noninvasive choice does not worsen mortality and the quality
      of care needed to improve patient outcome. From September 1st 1990 to September
      30th 1992, 775 patients (135 respiratory subjects) were admitted. The majority of
      these patients came from Coronary Intensive Units or Medical and Surgical
      Intensive Care Units. Noninvasive cardiorespiratory monitoring was assessed in
      these patients, to obtain their clinical improvement. After this post acute
      observance, our patients were followed during a stabilization programme in the
      cardiopulmonary rehabilitation division until a day-hospital or home care
      programme was carried out. By implementing the CPIIU principles in our department
      we have reduced the number of deaths and the necessity for Intensive Care Unit
      admission (from 19 to 9.6%). The estimated risk of death proposed by Apache score
      was higher than that recorded in our patients (estimated Apache = 25 and 6% for
      respiratory and cardiac patients, respectively; actual Apache = 10.4 and 3.1% for
      the same patients, respectively). Average hospitalisation days in our CPIIU was
      18 +/- 9. Our CPIIU showed a mean daily cost for each patient of $370.6.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8257970
TI  - NdYAG laser closure of a bronchopleural fistula.
AB  - We report the successful closure of a small bronchopleural fistula, which
      developed following right lower lobe lobectomy for squamous cell carcinoma. The
      patient underwent fibreoptic bronchoscopy diagnosis of possible bronchopleural
      fistula, manifested by cough and hydropneumothorax, following right lower lobe
      lobectomy. A small fistula was found at the stump of the right lower lobe. A
      chest tube with suction was placed for drainage before the therapeutic fibreoptic
      bronchoscopy. Through the flexible bronchoscope, using the tip of the bare laser
      fibre, a superficial erosion and bleeding around the fistula was created and
      coagulated by using a defocused yttrium aluminium garnet (Yag) laser beam. Close
      follow-up of the patient showed air leakage had stopped completely in 48 h. The
      chest tube was removed and the fistula never recurred. We suggest that this
      procedure may be used in selective patients with a small bronchopleural fistula.
      If successful, it can reduce the morbidity of more invasive surgical procedures.

PMID- 8257971
TI  - Occupational siderosis and welders' lung: a review.
AB  - Siderosis of the lung is generally assumed to be a benign condition, not
      associated with respiratory symptoms. A review of the literature suggests that
      this assumption may be incorrect, and that siderosis may lead both to symptomatic
      and functional changes. It is known that iron ore miners have a raised lung
      cancer mortality, but this has been attributed to smoking, or exposure to tars or
      radon. Mortality studies among iron workers (haematite miners, welders, iron
      foundry and steel workers) show, however, that an association exists between
      working with iron and death, both from lung cancer and other respiratory causes.
      A number of surveys have examined respiratory function and symptoms among
      welders. These indicate that welding is associated with obstructive airways
      disease. The effect of the welding fume on respiratory function and symptoms can
      be as great as that of smoking. Iron has also been shown to cause fibrosis in
      some cases. Small functional changes of restriction and loss of lung compliance
      are often due to iron alone. The fibrosis may be enhanced by associated silica
      exposure. A number of constituents of welding fume could, along with iron,
      contribute to pulmonary changes. The presence of siderosis may act as a good
      marker of exposure to fume and any resulting disability.

PMID- 8257972
TI  - Breathing disorders during sleep in chest wall diseases.
AB  - Chest wall deformity due to kyphoscoliosis may present with two altered breathing
      patterns during sleep; 1) progressive O2 desaturation particularly during REM
      sleep and 2) central apnoea also during REM sleep but rarely accompanied by O2
      desaturation. No typical breathing pattern abnormality is seen in the rigid spine
      syndrome.

PMID- 8257973
TI  - Sleep disorders in neuromuscular diseases.
AB  - This article reports the results of several studies on neuromuscular patients (9
      Duchenne's muscular dystrophy, 10 myotonic muscular dystrophy, 8 mitochondrial
      myopathies, 6 spinal muscular atrophy). An evaluation of respiratory function
      during wakefulness, a sleep questionnaire and an overnight polysomnography were
      performed in all patients. Recurrent hypoxaemia of variable degree was observed
      during sleep. In most cases, night-time hypoxaemia appears not to be predictable
      during wakefulness. Nocturnal hypoxaemia occurs in relation to apnoeas or
      hypopnoeas, mainly of central type, especially when these breathing
      irregularities occur during rapid eye movement (REM) sleep. Moreover, polygraphic
      sleep-apnoea patterns, as defined by international criteria, seem to be an
      infrequent condition, except for those neuromuscular diseases, characterized by
      an involvement of the central nervous system.

PMID- 8257974
TI  - The effect of ventilatory muscle training on respiratory function and capacity in
      ambulatory and bed-ridden patients with neuromuscular disease.
AB  - Most patients with neuromuscular disease develop muscle weakness, including the
      ventilatory muscles leading to respiratory difficulty and, at times, respiratory
      insufficiency. We studied the effect of ventilatory muscle training on the
      ventilatory function and capacity of patients with various types of neuromuscular
      disease. The ambulatory patients were divided into three major groups. Group I (n
      = 6) patients with motor neuron disease (MND), such as amyotrophic latera
      sclerosis; Group II (n = 11) patients with myoneural junction disease (MNJ), such
      as myasthenia gravis and: Group III (n = 7) patients with muscle diseases such as
      progressive muscular disease. Patients were evaluated for their neuromuscular
      diagnosis and status of the disease. A complete physical examination and the
      various neuromuscular tests were performed. A complete respiratory evaluation was
      applied: pulmonary function tests (PFT), maximum inspiratory pressure (MIP).
      Patients then started ventilatory muscle training by resistive breathing, as a
      prophylactic treatment, for 10 min, three times daily, with a resistance which
      would induce fatigue. All tests were repeated every six weeks, and the results
      were as follow: forced vital capacity (FVC) changed from 38.8 +/- 12.3 to 53.2 +/
      9.6% (NS) of predicted value in group I, from 49.8 +/- 8.7 to 66.1 +/- 7.5% (p <
      0.002) in group II, and from 47.0 +/- 7.5 to 53.3 +/- 7.6% (p < 0.04) in group
      III. Forced expiratory volume in one second (FEV1) was 34.8 +/- 11.0, 46.3 +/- 5,
      and 45.1 +/- 9% for the three groups, respectively, and did not change with
      training.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257975
TI  - Nutritional factors in the pathogenesis and therapy of respiratory insufficiency
      in neuromuscular diseases.
AB  - Malnutrition is a serious threat to patients with neuromuscular disease and
      marginally-compensated respiratory muscle weakness. It causes atrophy of
      inspiratory muscles, further weakening them. It reduces respiratory drive,
      potentially aggravating respiratory failure, either directly or indirectly, by
      promoting atelectasis and pneumonia, and it contributes strongly to such
      patients' risk of infection, their most common cause of death. In treating such
      patients, it must be remembered that abrupt increases in nutritional support,
      particularly with high percentages of carbohydrates, will increase CO2
      production, potentially worsening ventilatory failure. Certain selected
      neuromuscular disease patients benefit from specific nutritional treatments
      (carnitine for carnitine deficient patients, high-calorie diets for muscular
      dystrophy and acid-maltase deficiency). Finally, the amino acid, fat, and nucleic
      acid content of the diet affects the immune response in beneficial or harmful
      ways, that are just now being elucidate. The potential for useful nutritional
      interventions in patients with neuromuscular diseases has never looked better,
      but is not yet fully realized. The challenges for the future will be to work out
      the beneficial and harmful effects of the various nutrients in the various
      diseases, to find ways to rapidly identify patients who will benefit, and to
      determine the safest, least uncomfortable, and most effective methods of delivery
      of the required nutrients.

PMID- 8257976
TI  - Comprehensive rehabilitation of the severely disabled ventilator-assisted
      individual.
AB  - The lives of many individuals with severe disability and paralytic/restrictive
      pulmonary conditions, which progress or worsen with time, can be significantly
      prolonged, and the quality of life greatly enhanced, by noninvasive or
      conservative rehabilitation interventions. These interventions are devised to
      maintain or improve the individual's orthopaedic, pulmonary, and functional
      status. The combination of orthopaedic surgery and rehabilitation can reverse or
      ameliorate musculotendinous contractures and scoliosis and, thereby, maintain
      optimal patient comfort, function, and the possibility for nursing or personal
      care. Recent advances in the use of computers, environmental control systems,
      robotics, etc., can increase upper extremity functional activities. Non-invasive
      methods of airway secretion evacuation and ventilatory support can permit
      individuals with little or no vital capacity to avoid acute pulmonary
      complications, intubation and tracheostomy indefinitely.

PMID- 8257977
TI  - Which patients should receive lung transplants?
AB  - Lung transplantation is a therapeutic option for selected patients with end-stage
      respiratory failure from a variety of pulmonary vascular and parenchymal lung
      diseases. Early problems due to ischaemic dehiscence of the bronchial anastomosis
      were avoided with heart-lung transplantation where the coronary bronchial
      collateral circulation remains intact. With the increase in number of cardiac
      transplantation, the number of heart-lung blocks available for heart-lung
      transplantation are declining significantly. Improved techniques now make double
      lung, bilateral single lung and single lung transplantations suitable
      alternatives to heart-lung transplantations for many patients, with good
      anastomotic healing and encouraging results. Patients should only be accepted
      onto the transplant waiting list if they have deteriorating chronic respiratory
      failure with a severely impaired quality of life. All patients require a detailed
      pre-transplant medical and psychosocial assessment. While the absolute
      contraindications to transplantation include pre-existing malignant disease,
      active aspergillus or mycobacterial infection, infection with HIV or hepatitis B
      and noncompliance with treatment, new haemostatic techniques have made it
      possible to treat many patients who have had previous thoracic surgery. Advances
      in immunosuppressive agents and post-operative medical care have led to improved
      survival and quality of life. However, obliterative bronchiolitis remains a
      serious problem. Demand will always be in excess of available human organs. It is
      hoped that the development of successful xenografting will enable more patients
      to benefit from lung transplantation.

PMID- 8257978
TI  - Respiratory measurements of occupational exposure to industrial solvents.
AB  - The authors report the parameters which rule the absorption and elimination of
      polluting solvent vapours in exposed subjects (ventilation, pulmonary capillary
      flow, solubility coefficients, environmental concentration, exposure times).
      These parameters are included in the equations showing the absorption and
      elimination indexes and lung clearances. The absorption and elimination indexes
      implied are discussed stressing their practical usefulness in the field of
      biological monitoring, industrial hygiene and in preventive medicine.

PMID- 8257979
TI  - Evidence for human immunodeficiency virus infection of the lung.
AB  - Pulmonary disease is a frequent manifestation in the terminal stages of acquired
      immune deficiency syndrome (AIDS), and is caused mainly by a number of
      opportunistic microorganisms, most commonly Pneumocystis carinii. Despite the
      extensive involvement of the lung in the pathogenesis of AIDS, until recently
      little was known about the role of human immunodeficiency (HIV). In this review
      we will discuss the cellular tropism and phenotypic characterisation of HIV
      strains isolated from the lung. The available literature on HIV infection of the
      lung is reviewed, and the mechanisms of HIV-induced pathogenesis in the lung is
      discussed.

PMID- 8257980
TI  - The impact of asthma guidelines on clinical practice. A review prepared for the
      GEPOR working group meeting, Milan, June 22-23 1993.
AB  - Guidelines on asthma management may be useful in defining optimal standards of
      care and as a basis for audit. They also have a role in the education of health
      professionals and offer a common approach for use by all who care for those with
      asthma. They should define the goals and outcomes expected from treatment and
      preferably outline several ways in which they may be achieved. It should be made
      clear when the recommendations are based upon the results of clinical trials and
      where they merely reflect current clinical practice. Areas for future research
      should be clearly outlined. The production of guidelines is only likely to
      influence patient care, if the guidelines are adapted and made relevant to
      individual districts or health establishments. There needs to be a realisation
      that they contain much more than advice about drug treatments. A more patient
      centred approach to management and attention to patient education is necessary if
      they are to be effective in reducing the morbidity associated with this common
      condition.

PMID- 8257981
TI  - Impact of education on treatment compliance in patients with asthma.
AB  - Poor or non-compliance with therapy is a common problem, in patients with asthma,
      but one which has been poorly and infrequently studied both in clinical trials
      and in general practice. A common reason proposed for poor compliance is that if
      the patient fails to understand their disease process and the mode of action of
      therapy, then there is little motivation to follow the prescribed regimen. There
      has been a wealth of asthma educational programmes developed over the last 10
      yrs. Booklets, audio cassettes and, more recently, videos, explaining asthma,
      have all become available, but there is still some doubt as to whether such
      knowledge alters patient behaviour and improves compliance with therapy.
      Modifying behaviour and improving asthma control may be achieved with specific
      instruction, such as a self-management plan where the patient has greater control
      of his or her own condition.

PMID- 8257982
TI  - Smoking cessation and respiratory function.

PMID- 8257983
TI  - Drug resistant tuberculosis.

PMID- 8257984
TI  - Molecular diagnostics: past, present, and future.
AB  - Molecular diagnostics (MDx) is currently a clinical reality that has its roots
      deep in the study of gene function, structure, and regulation. The multitude of
      human mutations identified in the various genetic diseases can now be assayed in
      the clinical molecular diagnostics laboratory. The polymerase chain reaction
      (PCR) has facilitated the transition from the research to the clinical
      laboratory, however, many methods which scan and identify known mutations may not
      be applicable in a clinical environment. A few of these methods are discussed and
      one technology that is well suited for clinical use is suggested. Well-trained
      personnel, regulation of MDx laboratories, and automation are a few of the
      requirements that will carry us into the promising future of molecular diagnosis.

PMID- 8257985
TI  - How sensitive is PCR-SSCP?
AB  - Single-strand conformation polymorphism analysis (SSCP) is a rapid method for
      detection of minor sequence changes in polymerase chain reaction-amplified DNA.
      Since the first reported use of SSCP in 1989 (Orita et al., 1989), this technique
      has been used widely to detect mutations in oncogenes, tumor suppressor genes,
      and genes responsible for genetic diseases. Published mutations that have been
      detected using this technique include base substitutions, small insertions and
      deletions, and rearrangements. This technique has also been applied for the
      detection of DNA polymorphisms at various loci of the human genome (reviewed by
      Hayashi, 1991; Hayashi, 1993). However, many factors can influence the
      sensitivity of SSCP, and its optimization is highly empirical. In this review, we
      estimate the percentage of mutations that can be detected by this technique under
      various controlled conditions, and describe some critical elements affecting
      sensitivity.

PMID- 8257986
TI  - Mutational analysis of SRY in XY females.
AB  - The Y chromosome located gene SRY (sex determining region Y gene) was identified
      in the search for the mammalian testis determining factor (TDF). Approaches for
      evaluating SRY as a candidate for TDF included the finding of mutations in SRY in
      the genomes of patients with failed testis development (XY females or 46,XY
      gonadal dysgenesis) and the production of female to male sex reversed mice
      transgenic for the mouse homologue of SRY, [Sry]. Since the initial use of XY
      females in the proof of SRY/TDF identity, many more patients have been analysed
      using different techniques and more mutations identified. A total of 11 mutations
      in SRY have now been described, all in the DNA-binding HMG-box region of the
      gene, and all in patients with apparently complete gonadal dysgenesis.
      Surprisingly, three familial SRY mutations have been identified, where the
      phenotype is either fertile male or sterile sex-reversed female. Estimates of the
      proportion of XY females mutant for SRY average at approximately 15%. Reasons for
      the low frequency of SRY mutations in XY sex reversal could be the presence of
      mutations in regions of SRY not yet discovered, the occurrence of mutations that
      give the same phenotype, perhaps in genes close to SRY in the testis determining
      pathway, or incorrect diagnosis of complete gonadal dysgenesis.

PMID- 8257987
TI  - Genomic instability occurs in colorectal carcinomas but not in adenomas.
AB  - Genomic instability, as demonstrated by the presence of additional alleles at
      short tandemly repeated (STR) loci, has recently been observed in colorectal
      tumours from individuals with hereditary nonpolyposis colorectal cancer (HNPCC),
      and in some sporadic tumours. These neoplasms have been called replication error
      positive (RER+). In this study, we confirm the presence of genomic instability in
      a proportion of unselected colorectal carcinomas but find no evidence of
      instability in adenomas. We further report replication errors in a
      tetranucleotide sequence, and in STRs within two tumour suppressor genes. 108
      colorectal adenocarcinomas and 46 adenomas were analysed for the presence of
      variant bands at 4-15 microsatellite markers. Seven (6.5%) of carcinomas were
      RER+, four of which originated from the proximal colon. Analysis of the adenomas
      and of matched adenoma-carcinoma and carcinoma-metastatic samples from four
      patients suggests that the replication errors may occur during the development of
      carcinomas but are rare in adenomas.

PMID- 8257988
TI  - Single-strand conformation polymorphism (SSCP) analysis of the molecular
      pathology of hemophilia B.
AB  - In the present study, we report the application of polymerase chain reaction
      single-strand conformation polymorphism (PCR-SSCP) analysis to the screening of
      seven functionally important factor IX gene (FIX) regions (total length 2.66 kb)
      in 9 unrelated haemophilia B patients of Portuguese or African origin. In eight
      of the patients an altered migration pattern of single-stranded DNA was observed.
      Direct sequencing of the relevant DNA fragments unveiled the following sequence
      alterations: two novel mutations, namely FIXBarcelos Thr-380-Pro and FIXLousada
      9bp insertion at position 31,309 or 31,318; five mutations previously reported in
      other ethnic groups (FIXPorto Arg-145-His, FIXLuanda Gly-207-Arg, FIXPenafiel Arg
      248-Gln, FIXSesimbra Arg-333-Gln, FIXCascais Arg-333-Stop); and a normal variant,
      G-->T transvertion at position 6,596 in intron 2. We propose hypothetical models
      for the generation of the 9 bp duplication (FIXLousada). We have performed
      molecular modeling studies in order to predict the structure of the variant FIX
      molecules.

PMID- 8257989
TI  - Molecular screening of Japanese patients with Gaucher disease: phenotypic
      variability in the same genotypes.
AB  - Gaucher disease is the most prevalent sphingolipidosis, characterized by genetic
      deficiency of lysosomal hydrolase glucocerebrosidase, and is inherited in an
      autosomal recessive manner. To characterize the molecular basis of Gaucher
      disease in Japan, we analyzed for the presence of the two known mutations (1448C
      and 754A) in the glucocerebrosidase gene of 15 patients (14 families) with
      Gaucher disease by selective amplification and restriction endonuclease analysis.
      We found that the 1448C and 754A mutations occurred in all three clinical
      subtypes of Japanese Gaucher disease patients. The 1448C mutation was found on 12
      (40%) out of 30 chromosomes (44% allele frequency in nonneuronopathic form, and
      33% in neuronopathic forms), while homozygosity for this mutation was only found
      in two nonneuronopathic patients (age of 1 year 6 months and 7 years). We
      detected the 754A mutation on 6 (20%) out of 30 chromosomes. No patient was
      homozygous for 754A mutation. Furthermore, we identified four patients who were
      compound hetrozygote for 754A and 1448C. One of these was a type 3 Gaucher
      patient, but the other three patients were free from central nervous system
      manifestations at the time of observation. These results indicate that phenotypic
      presentation of Gaucher disease including the presence of nervous manifestation,
      progression, and severity of disease, may be affected by other genetic,
      environmental, or developmental factors, as well as the glucocerebrosidase
      genotype.

PMID- 8257990
TI  - Base substitutions in the human dystrophin gene: detection by using the single
      strand conformation polymorphism (SSCP) technique.
AB  - We have established the experimental conditions to screen twenty regions of the
      dystrophin gene using the method of single-strand conformational polymorphism
      (SSCP) analysis. The aim of this study was to identify point mutations in
      patients with Duchenne or Becker muscular dystrophy (DMD or BMD) who have no
      gross DNA rearrangements detectable by Southern blot analysis or multiplex exon
      amplification. The investigation of thirteen patients using this procedure
      resulted in the detection of seven sequence polymorphisms (four identified in
      this study) that will be useful allelic markers in familial DNA analysis. Three
      rare sequence variants could be found (two of them being novel variants) but we
      were unable to demonstrate mutations that could be clearly sufficient to be
      responsible for the phenotype. This analysis confirmed the efficiency of the SSCP
      technique for the detection of nucleotide substitutions. Application of this
      approach to mutation or polymorphism detection to other exons of the gene will
      improve carrier and prenatal diagnosis.

PMID- 8257991
TI  - Identification of two novel beta zero-thalassemia mutations in a Filipino family:
      frameshift codon 67 (-TG) and a beta-globin gene deletion.
AB  - The frequency of beta-thalassemia alleles among Filipinos is estimated to be
      0.02, although little is known about the actual mutations represented in this
      population. Here, we describe a Filipino family in which a child has severe beta
      thalassemia major. Molecular studies of the family revealed that the proband is a
      compound heterozygote for two previously unreported beta zero-thalassemia
      alleles: a frameshift mutation (-TG) at codon 67 and a deletion of the entire
      beta-globin gene. The 5' endpoint of this novel deletion is located approximately
      3.9 kb to approximately 4.3 kb upstream of beta-globin gene, and the deletion
      extends 3' beyond the beta-globin gene for an undetermined distance. The
      occurrence of two novel beta-thalassemia alleles in a single family suggests that
      the Filipino population may have a unique spectrum of beta-thalassemia alleles.

PMID- 8257992
TI  - A de novo G+1-->A mutation at the alpha 2(I) exon 16 splice donor site causes
      skipping of exon 16 in the cDNA of one allele of an OI type IV proband.
AB  - We have investigated the procollagen, collagen, alpha 2(I) mRNA, and DNA of a
      proband with type IV OI. The proband synthesized two alpha 2(I) chains, one with
      normal electrophoretic migration and one more rapidly migrating. The fast alpha
      2(I) chain was relatively retained within the cell and was present in collagens
      synthesized in the presence of alpha,alpha'-dipyridyl. The alpha 2(I) cyanogen
      bromide peptide CB 4-2 contained both normal and rapidly migrating components.
      Thermal stability of helices containing the rapidly migrating alpha 2(I) chain
      was reduced 6 degrees C. Parental fibroblast collagens were normal. RNA/RNA
      hybrids between proband total RNA and antisense riboprobe complementary to alpha
      2(I) nt 236-1390 were digested with RNase A and T1. Digestion products seen
      exclusively in the proband suggested a structural change in the region coding for
      exons 16-19. The region which hybridized to the riboprobe was amplified using RNA
      PCR and subcloned. Multiple restriction enzyme digestions of the two subcloned
      alleles suggested a structural change localized to the region coding for exons 16
      17. Sequencing revealed a deletion of the 54 bp comprising exon 16 in the cDNA of
      one allele. The region of the proband's genomic DNA spanning exons 15-17 was
      amplified by PCR. The subcloned genomic fragments of each allele were
      distinguished by RNA/DNA hybrid analysis using a riboprobe complementary to
      normal genomic DNA from this region. Sequencing revealed a G+1-->A mutation at
      the exon 16 donor site in one allele. The mutation eliminates a StyI
      site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8257993
TI  - Detection of sequence variations in the human insulin-receptor gene by parallel
      denaturing gradient gel electrophoresis.
AB  - We developed a parallel denaturing gradient gel electrophoresis (DGGE) protocol
      to maximize the detection of nucleotide variants in the DNA sequence coding for
      the mature insulin receptor and in splice site junctions. The melting behaviours
      of exons 2 to 22 and flanking intronic sequences were computer-simulated using
      two programs, MELT87 and SQHTX. The data obtained from computer analysis were
      used to select primers for amplification by polymerase chain reaction and optimal
      electrophoretic conditions. The ability of this protocol to detect nucleotide
      changes at the insulin-receptor locus was assessed by studying amplified DNA of a
      patient with leprechaunism whose insulin-receptor mutations were known and by
      screening the insulin-receptor gene for polymorphisms in a population of
      unrelated caucasian individuals. Our results demonstrate that this DGGE protocol
      is sensitive since it detected (1) sequence variants reported to be undetectable
      by means of parallel DGGE, (2) previously characterized insulin-receptor
      nucleotide variants, and (3) unreported polymorphisms at the insulin-receptor
      locus of caucasian individuals. It is also simple as perpendicular denaturing
      gradient gels are not required. Application of this protocol will facilitate the
      search for molecular defects underlying the pathogenesis of insulin resistance
      observed in genetic syndromes of severe insulin resistance as well as in other
      metabolic disorders. In addition, its ability to detect several regions of the
      insulin-receptor gene displaying a number of common polymorphic sites and being
      multiallelic will contribute to linkage studies in families with diabetic and/or
      insulin-resistant subjects.

PMID- 8257994
TI  - Optimization of the single-strand conformation polymorphism (SSCP) technique for
      detection of point mutations.
AB  - The efficiency of detection of single base substitutions by single-stranded
      conformation polymorphism (SSCP) analysis was tested on 86 randomly distributed
      point mutations in a 193-bp-long DNA fragment of the mouse beta-globin gene.
      Multiple parameters were varied, including electrophoresis temperature, buffer
      concentration, gel concentration, acrylamide-to-bis-acrylamide ratio, and/or
      addition of different compounds to the gel matrix. Gels with a higher
      concentration of acrylamide and lower crosslinking gave optimal separation, and
      all 86 mutations can be clearly distinguished from the wild type on a 5% or 7.5%
      (2.6% C) acrylamide gel at 4 degrees C. Most of the mutations are also resolvable
      from wild type on gels with 5% urea or formamide, or 10% dimethylsulfoxide or
      sucrose. The relative position of the purine and pyrimidine-rich single strands
      were followed by an asymmetric PCR-SSCP technique. We found that most of the
      informativity comes from the purine rich strand, which appears to be much more
      sensitive to changes in the gel. The position or type of mutation showed no
      correlation with its ability to be detected. However, the neighboring base
      sequence around the mutation appears to have an effect on mobility. For example,
      A-->G substitutions in GC-rich regions significantly increase the mobility shift
      of the purine-rich strand, while most G-->A changes decrease it. We conclude that
      SSCP is a very efficient method for the detection of point mutations, if the
      parameters that effect the separation are optimized for a particular DNA
      fragment.

PMID- 8257995
TI  - Tay-Sachs disease in an Israeli Arab family: Trp26-->stop in the alpha-subunit of
      hexosaminidase A.

PMID- 8257996
TI  - The first genetic marker detected in the promoter region of the thyroid
      peroxidase gene by single-strand conformational polymorphism analysis.

PMID- 8257997
TI  - Transthyretin ALA 71: a new transthyretin variant in a Spanish family with
      familial amyloidotic polyneuropathy.

PMID- 8257998
TI  - Epidemiology of critical limb ischaemia: north Italian data.
AB  - OBJECTIVES: We confronted the difficult problem of obtaining accurate
      epidemiological data on critical leg ischaemia. METHODS: Three different
      approaches were used. 1) A prospective study, over a total period of 7 years, on
      the incidence of critical leg ischaemia in 200 patients suffering from
      claudication and in 190 controls. 2) A prospective study, over a period of 3
      months, on critical leg ischaemia hospitalization in a sample of hospitals
      located in a Region of Northern Italy (Lombardy). 3) Encoding the amputations
      performed in the hospitals in two regions of Northern Italy: for 6 months in
      Lombardy and for 2 years in Emilia Romagna. RESULTS: The data obtained through
      the three different methodological approaches provided results that were
      substantially equivalent in order of magnitude. The incidence in the population
      aged > 45 years turned out to be 450/million/year for critical leg ischaemia and
      112/million/year for amputations. In the sample of hospitals in Lombardy, the
      incidence in the population aged > 45 years was 652/million/year for critical leg
      ischaemia and 160/million/year for amputations. The incidence of amputations in
      Lombardy and Emilia Romagna in the population aged > 45 years was
      577/million/year for critical leg ischaemia and 172/million/year for amputations
      in Lombardy and 530/million/year for critical leg ischaemia and 154/million/year
      for amputations in Emilia Romagna. CONCLUSION: The results indicate an incidence
      of critical leg ischaemia and amputations lower than expected in the samples
      studied. It is known that Italy is a country with one of the highest rates of
      "cardiovascular protection". Therefore, genetic and dietary factors probably play
      an important role also in the development of critical leg ischaemia and in the
      consequent incidence of amputations.

PMID- 8257999
TI  - Relationship of omega-3 fatty acid supplementation to plasma lipid peroxidation
      in predialysis patients with hypertriglyceridaemia.
AB  - OBJECTIVES: Since it has been suggested that omega-3 polyunsaturated fatty acids
      (PUFA) may be an efficient treatment for dyslipoproteinaemia and renal function
      in uraemic patients, this study was carried out to evaluate the potential adverse
      effects of polyunsaturated acids on lipid peroxidation in patients with chronic
      renal failure. PATIENTS AND METHODS: Five uraemic predialysis patients with
      various renal diseases presenting progressive renal failure and moderate
      hypertriglyceridaemia (1.93 +/- 0.60 g/L) in comparison with the reference values
      of our laboratory (0.88 +/- 0.20 g/L) were given 6 g of fish oil per day for 6
      months in the form of Maxepa capsules containing a low dose of tocopherol acetate
      (10.5 mg/day). During the treatment we investigated the effect (expected to be
      beneficial) of n-3 PUFA on triglyceride plasma levels and renal function. We also
      investigated the potential side effect of such a treatment on lipid peroxidation.
      RESULTS: A moderate decrease of triglycerides early after the introduction of the
      treatment (1.93 +/- 0.6 g/L vs 1.33 +/- 0.58 g/L; 0 vs 0.5 months) was observed.
      In all patients, lipid peroxides measured as thiobarbituric acid reactants
      increased early after the introduction of the n-3 PUFA therapy (2.8 + 0.8 vs 3.76
      +/- 0.15 mumol/L; 0 vs 0.5 months). Organic hyperoxides were significantly
      different in these patients compared with laboratory values, but they did not
      increase significantly during the treatment. CONCLUSION: It must be noted that
      polyunsaturated fatty acids should be used with caution in predialysis patients.

PMID- 8258000
TI  - Spontaneous pneumothorax in patients with the human immunodeficiency virus: study
      of eight cases.
AB  - OBJECTIVE: To evaluate the risk factors and the natural history of spontaneous
      pneumothorax in patients with human immunodeficiency virus infection (HIV).
      METHODS: We studied eight HIV infected patients with spontaneous pneumothorax.
      Variables assessed included sex, age, risk factor for HIV infection, use of
      Pneumocystis carinii pneumonia prophylaxis, total and CD4 positive lymphocyte
      count, previous history of Pneumocystis carinii pneumonia or pulmonary
      tuberculosis, chest X-ray film, presence of simultaneous opportunistic infection,
      partial pressure of oxygen in arterial blood gas determination and clinical
      outcome. RESULTS: The patients were predominantly male and intravenous drug
      abusers. Mean age was 28 years (range: 21-44). Five patients had acquired
      immunodeficiency syndrome, 2 oral candidiasis and one asymptomatic HIV infection.
      Three had previously had Pneumocystis carinii pneumonia and six a concurrent
      opportunistic infection. No one was receiving aerosolized pentamidine
      prophylaxis. The pneumothorax was bilateral in two cases. Chest tube evacuation
      was required in seven, and six patients died. Only two patients without
      opportunistic infection were discharged. CONCLUSIONS: We conclude that
      spontaneous pneumothorax is a serious problem with high mortality in patients
      with advanced human immunodeficiency virus infection. Previous or active
      Pneumocystis carinii pneumonia appear to be a risk factor for developing
      pneumothorax. It seems to be independent of aerosolized pentamidine use.

PMID- 8258001
TI  - Low serum testosterone: a special feature of hepatocellular carcinoma.
AB  - OBJECTIVES: The possible role of sex hormone imbalance in hepatocellular
      carcinogenesis was investigated. PATIENTS AND METHODS: Ten men with
      hepatocellular carcinoma (HCC) and cirrhosis, 10 men with HCC without cirrhosis,
      12 men with cirrhosis of various aetiologies, 8 men with secondary liver tumours
      and 10 normal men were studied. Plasma levels of testosterone, androstenedione,
      oestradiol, sex hormone binding globulin follicle stimulating hormone and
      luteinizing hormone were determined for all patients. RESULTS: Patients of all
      groups had comparable levels of oestradiol, androstenedione, sex hormone binding
      globulin, luteinizing hormone and follicle stimulating hormone. Low testosterone
      values in the serum were found for all patients with primary liver disease. Low
      testosterone was found even in patients with primary HCC who did not have
      cirrhosis or liver failure serious enough as to be responsible for the reduction
      of testosterone levels. On the other hand patients suffering from secondary liver
      tumours had normal values of serum testosterone. CONCLUSIONS: These results
      present an indication that low serum testosterone is a special feature of
      hepatocellular carcinoma.

PMID- 8258003
TI  - Coronary angioplasty: from the conventional balloon technique to molecular
      biology and gene therapy.

PMID- 8258002
TI  - Mortality in pneumococcal meningitis: a multivariate analysis of prognostic
      factors.
AB  - OBJECTIVES: The mortality due to pneumococcal meningitis remains high, ranging
      from 15 to 60%. The purpose of this study was to analyze the prognosis of
      pneumococcal meningitis using a multivariate approach. The objectives were to
      select the most accurate initial mortality risk factors in pneumococcal
      meningitis and to determine an individual probability of death according to these
      prognostic factors. METHODS: The records of 105 consecutive cases of proven
      pneumococcal meningitis were retrospectively reviewed. The following parameters,
      recorded at presentation were considered for prognostic analysis: age, sex,
      duration of symptoms and antimicrobial chemotherapy before admission, underlying
      debilitating conditions, occurrence of seizures, pneumococcal bacteraemia or
      pneumonia, Glasgow coma scale score, Simplified Acute Physiological Score (SAPS),
      Cerebral Spinal Fluid (CSF) leucocyte count, CSF protein level, CSF glucose level
      and CSF/blood glucose ratio. Those parameters having a prognostic value after
      univariate logistic regression analysis were then entered into a multivariate
      stepwise logistic regression model. RESULTS: In multivariate analysis, a fatal
      outcome was best predicted by 4 variables. In descending order, these were the
      Glasgow coma scale score, age, CSF glucose level and concomitant pneumonia. The
      risk of dying was ten times higher in patients with Glasgow coma scale score < 7,
      seven times higher in patients older than 45 or having a CSF glucose level lower
      than 0.6 mmol/L and 4 times higher in patients with pneumonia. The logistic model
      provided an equation for the probability of dying that proved to have predictive
      values greater than 80% in determining the individual prognostic of pneumococcal
      meningitis. CONCLUSIONS: Our results are in agreement with most of previously
      published findings. We further demonstrated that the individual prognosis of
      pneumococcal meningitis could be accurately predicted with only 4 variables and
      highlighted the preeminent prognostic value of Glasgow coma scale score.

PMID- 8258004
TI  - Cardiopulmonary resuscitation preferences in the elderly.
AB  - OBJECTIVE: Many studies have examined the attitudes of elderly Americans towards
      cardiopulmonary resuscitation. A less formal approach to resuscitation decisions
      is usual in Europe, but few comparable studies have been reported in elderly
      European populations. We studied the views on resuscitation in a prospective
      series of elderly Irish patients. METHODS: We administered a standardized
      questionnaire to 100 elderly patients who did not have cognitive impairment,
      depression or terminal or life-threatening illness. Patients were asked if they
      could wish to be resuscitated following a cardiac arrest in their present state
      of health and in a number of hypothetical clinical situations. RESULTS: All of
      our patients would reject resuscitation in the event of severe functional or
      mental impairment. Even in their present state of health, only three patients
      would definitely opt for resuscitation, 74 patients would reject resuscitation,
      and the remainder would leave the decision to their family or doctor.
      CONCLUSIONS: These results suggest that there are substantial differences in
      attitudes to resuscitation between Irish and American elderly patients. Further
      studies in other European populations are necessary.

PMID- 8258005
TI  - Drug-induced liver disease: pathogenetic mechanisms and histopathological
      lesions.

PMID- 8258006
TI  - Nitric oxide and the control of human vascular tone in health and disease.

PMID- 8258007
TI  - Rationale for the utilization of interleukin-4, an immune-recognition induced
      cytokine, in cancer immunotherapy.
AB  - Interleukin-2 use for advanced cancer treatment has demonstrated that cytokines
      are of interest not only in the field of immunology but also in oncology.
      Interleukin-2 is only one member of the ever-growing family of immune recognition
      induced lymphokines. Interleukin-4, a cytokine with pleiotropic effects, shares
      some common properties with interleukin-2. Availability of recombinant
      interleukin-4 has led to a better knowledge of this cytokine's functions, and
      also makes clinical trials possible. This brief review discusses the in vitro and
      in vivo data that support a potential use of interleukin-4 in cancer
      immunotherapy.

PMID- 8258008
TI  - Delayed multiorgan non-neoplastic damage after exposure to radiotherapy in
      infancy.

PMID- 8258009
TI  - Lacrymal gland enlargement as a presenting feature of Wegener's granulomatosis.

PMID- 8258011
TI  - Hairy-cell leukaemia and sarcoidosis.

PMID- 8258010
TI  - Evidence for priming and activation of neutrophils early after coronary
      angioplasty.
AB  - OBJECTIVES: Percutaneous transluminal coronary angioplasty (PTCA) induces deep
      arterial wall injury and transient ischaemia. The aim of this study was to
      demonstrate that PTCA could result in priming or activation of the neutrophils
      and the complement system. METHODS: Blood was drawn from the coronary sinus
      before and immediately after PTCA in 7 patients and before and immediately after
      coronary angiography in 7 patients (to ensure that the changes observed after
      PTCA were not solely related to the angiographic procedure). Neutrophil priming
      was assessed ex vivo by whole blood chemiluminescence stimulated in vitro by
      formyl-methionyl-leucyl-phenylalanine, phorbol myristate and opsonized zymosan.
      Neutrophil activation was assessed by measurement of plasma lactoferrin. RESULTS:
      Whole blood chemiluminescence increased after PTCA, regardless of the stimulus
      used, while it did not after arteriography. After PTCA, lactoferrin increased 2
      fold (p < 0.02) whereas after arteriography a non-significant increase was
      observed. Neutrophil count and adherence properties were not modified by either
      PTCA or arteriography. Total haemolytic complement (CH50), C3, C4 and B factor
      decreased slightly (7 to 16%) after both PTCA and arteriography. CONCLUSIONS:
      Early after PTCA, the neutrophil oxidative response, assessed by stimulated whole
      blood chemiluminescence, increased, suggesting a "priming" effect of PTCA on
      neutrophils. In addition, plasma lactoferrin levels increased, indicating
      neutrophil activation. Finally, there was a mild global activation of the
      complement system, most likely related to the contrast agent, and which may play
      a role in the "priming" process. Neutrophil priming and activation may
      participate in several phenomena occurring after angioplasty such as enhanced
      vasoconstriction and post-ischaemic myocardial dysfunction. In addition, it may
      participate in triggering local inflammatory processes.

PMID- 8258012
TI  - Melatonin in patients with pituitary tumours.

PMID- 8258013
TI  - Idiopathic membranous nephropathy: new therapeutic trends.

PMID- 8258014
TI  - Persistence of Pseudomonas aeruginosa strains in seven cystic fibrosis patients
      followed over 20 months.

PMID- 8258015
TI  - Circulating anticoagulant and antiplatelet immunoglobulin in autoimmune thyroid
      disease.

PMID- 8258016
TI  - Tibial artery thrombosis due to varicella zoster virus in a transplant recipient
      under cyclosporine.

PMID- 8258018
TI  - The Halcion scare: hyperbole or honest truth?

PMID- 8258017
TI  - Candida arthritis treated with intra-articular amphotericin B.

PMID- 8258019
TI  - Present management of Graves' hyperthyroidism: an effective but symptomatic
      approach.

PMID- 8258020
TI  - Treatment of Graves' disease: effects of the administration of L-thyroxine
      associated with methimazole as a single daily dose.
AB  - OBJECTIVES: To reduce the number of tablets to be administered daily during
      antithyroid drug (ATD) treatment of Graves' disease (GD) and to evaluate the
      effectiveness of adding thyroxine after the patients had become euthyroid during
      methimazole therapy. PATIENTS AND METHODS: All patients were given gelatin
      capsules with 30 mg of methimazole 2 times per day for 4-6 weeks, followed by two
      capsules with 20 mg of methimazole and 75 micrograms of thyroxine to be taken
      once a day for 18-24 months. Thirty patients with Graves' disease without
      previous treatment for hyperthyroidism were included. Two were lost to follow-up
      and 28 (24 women and 4 men; age range 14-53 years; mean 34.2 years) were followed
      for 18 to 24 months with methimazole and thyroxine medication plus an additional
      2 years after the treatment was suspended. After completion of the study the
      patients were, retrospectively, divided in two groups: group 1 (G1, n = 20)
      patients considered to be in remission, and group 2 (G2, n = 8) with persistent
      active Graves' disease. RESULTS: All patients in group 1 had a significant
      reduction in the glandular mass, as estimated by ultrasonographic studies (mean
      +/- SD 67 +/- 13 g to 18 +/- 3 g, p < 0.01) whereas subjects in group 2 had no
      significant reduction in glandular mass (67 +/- 14 g to 53 +/- 16 g).
      Thyroglobulin levels (mean +/- SD) in G1 were 54 +/- 55 micrograms/L at baseline
      and decreased to 15 +/- 9 micrograms/L (p < 0.001), and in G2 thyroglobulin
      concentrations did not decrease significantly after therapy (58 +/- 20
      micrograms/L vs 44 +/- 22 micrograms/L). Also, levels of thyroid-stimulating
      hormone receptor inhibiting antibody (TRAb) only decreased in G1 (49-21% to 8 +/-
      5%; p < 0.001). Nineteen patients (all from G1), were euthyroid 2 years after
      treatment withdrawal, indicating a remission rate of 67.8%. CONCLUSION: The
      administration of L-thyroxine during anti-thyroid drug treatment, with subsequent
      inhibition of thyroid-stimulating hormone secretion, may be an important factor
      in glandular mass reduction, decreasing both the production of antibodies to
      thyroid-stimulating hormone receptors and the frequency of recurrence of
      hyperthyroidism.

PMID- 8258021
TI  - Prevalence of aortic valve stenosis in patients affected by gastrointestinal
      angiodysplasia.
AB  - OBJECTIVES: Angiodysplasia is considered to be an important cause of
      gastrointestinal bleeding in the elderly. An association between idiopathic
      gastrointestinal bleeding and aortic valve stenosis has been reported in up to
      25% of the patients. The association between angiodysplasia mainly of the right
      colon and aortic valve stenosis has been suggested, but is not proven. The aim of
      this study was to examine the prevalence of aortic valve stenosis in patients
      with gastrointestinal angiodysplasia. METHODS: We studied retrospectively 83
      patients submitted to gastrointestinal endoscopy and found affected by
      angiodysplasia. Of them 24 (16M and 8F) had died from causes unrelated to
      cardiovascular diseases. The 59 patients still alive (27M and 32F) underwent a
      complete clinical, electrocardiographic and echocardiographic (M-mode, B-mode,
      pulsed and continuous-wave Doppler) evaluation. RESULTS: Fifteen patients (25%)
      had a normal examination, both clinical and echocardiographic. Eleven (19%) had
      minor cardiac abnormalities but had no murmurs. Although no murmurs were present
      in 15 patients (25%), some echocardiographic abnormalities such as aortic leaflet
      sclerosis, mitral annular calcification, their association, or trivial mitral
      regurgitation detectable only at PW-Doppler were found. In 18 patients (31%) both
      systolic murmurs and valvular abnormalities, as revealed by echocardiographic
      examination, were detected: 10 had a regurgitant and 8 an ejectional murmur; of
      these only 1 (1.6%) had a true severe calcified aortic valve stenosis at echo
      Doppler examination. CONCLUSIONS: The low prevalence of aortic valve stenosis in
      patients with gastrointestinal angiodysplasia (1/59 or 1.6%) in this
      retrospective study argues against the association of gastrointestinal
      angiodysplasia and aortic valve stenosis.

PMID- 8258022
TI  - Thyroid function tests in non-alcoholic cirrhotic patients with hepatic
      encephalopathy.
AB  - OBJECTIVES: Changes in thyroid hormone levels in non-alcoholic cirrhotic patients
      with hepatic encephalopathy were investigated in order to determine whether
      thyroid function tests could be a useful prognostic indicator for acute outcome.
      METHODS: Patients with hepatic encephalopathy due to non-alcoholic cirrhosis were
      studied at Erciyes University Hospital, Kayseri, Turkey, between August 1990 and
      October 1991. Nine of them were males and eight females, with ages ranging
      between 22 and 69 years. Eleven cirrhotic patients who had no encephalopathy of
      any degree comprised the control group. Patients with hepatic encephalopathy were
      divided into two groups: survivors and non-survivors. The levels of serum
      triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), free T3 (FT3) and free
      T4 (FT4) were obtained in both patients with and without encephalopathy.
      Alterations of thyroid function tests and their relation to acute outcome were
      evaluated. RESULTS: Serum T3 and FT3 levels were significantly lower in the
      patients who died of encephalopathy compared with controls (p < 0.05). Serum FT3
      and FT4 were also lower in the survivors compared with those of the cirrhotic
      controls (p < 0.05). Albumin was found to be the unique and most important
      prognostic factor with a difference between survivors and cirrhotic controls (p <
      0.05). CONCLUSIONS: These data suggest that patients with liver disease due to
      non-alcoholic cirrhosis are under great risk for hepatic encephalopathy when they
      have low FT3 levels. The decrease of serum T3 and albumin levels could be
      considered as indicators of poor prognosis for acute outcome.

PMID- 8258023
TI  - The Belgian system to control indications for the implantable defibrillator: a
      model for other European countries?
AB  - OBJECTIVES: The purpose of this study was to assess the value of the Belgium
      system to control the indications for the implantable defibrillator. METHODS: We
      reviewed the answers of our official organization (Riijksinstituut voor Ziekte en
      Invaliditeitsverzekering-RIZIV) to our requests of implantable defibrillators in
      49 patients in 1990, 1991 and the first months of 1992. In 1988 and in agreement
      with the RIZIV, 15 implants per year were allowed, but this number had been
      extended to 100 in 1992. RESULTS: There was an increasing first refusal rate from
      1990 (0%) to 1991 (25%) and 1992 (42%), which was caused by: a) Difficulties to
      deal with indications for unusual diseases, particularly young patients with
      cardiac arrest and a structural normal heart; b) Possible distrust by the RIZIV
      towards the physician when the number of requests increases over time. However,
      all patients for whom a defibrillator was requested ultimately had it implanted.
      CONCLUSIONS: In the most ideal type of cooperation between official organisms and
      implanting physicians, such as the Belgian system, the official organization has
      to realize that uncommon patients with disputable indications exist. To avoid
      refusal of reimbursement in these cases, the decision taken by the treating
      physician can be accepted only on condition that the mutual relationship between
      both parties is based on open communication, mutual respect, and trust. The
      Belgian system provides care to all patients requiring a defibrillator with costs
      to society which are very acceptable. The Belgian system may be an excellent
      model for countries without clear regulations for reimbursement of implantable
      defibrillators.

PMID- 8258024
TI  - HIV-related demyelinating disease.
AB  - True demyelination, or at least a leukoencephalopathy with predominant
      involvement of myelin, may occur in many neurological complications of human
      immunodeficiency virus (HIV)-infection, resulting from various mechanisms which
      are not all well understood. These include lesions directly related to infection
      of the nervous tissue by HIV, opportunistic infections and lymphomas secondary to
      the cell-mediated immunodeficiency, and changes due to other general or systemic
      complications of acquired immunodeficiency syndrome (AIDS). HIV-induced pathology
      of the nervous system includes HIV-specific disease, due to direct infection of
      the nervous system by the virus. This is characterized by the presence of
      distinctive multinucleated giant cells and white matter changes, HIV encephalitis
      and HIV leukoencephalopathy, which may overlap in one third of cases. The
      pathogenesis of myelin destruction is unclear. Direct infection of neurons or
      glial cells has never been demonstrated. Indirect immunopathologic, toxic,
      metabolic, or vascular mechanisms secondary to infection of monocytes/macrophages
      are more likely. Less specific HIV-associated central nervous system (CNS)
      pathology including vacuolar myelopathy, and vacuolar leukoencephalopathy are
      characterized by numerous vacuolar myelin swellings in spinal or cerebral white
      matter. The exact aetiopathological relationship of these changes to HIV
      infection is uncertain. It seems likely that factors other than, or additional
      to, HIV infection play a role in their causation. Apart from these changes which
      usually occur at the late stages of the disease, acute perivenous inflammatory
      leukoencephalopathy, presenting either as acute haemorrhagic leukoencephalopathy,
      acute demyelinating perivenous encephalitis, or acute multiple sclerosis-like
      leukoencephalopathy revealing HIV-infection occur in rare cases.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258025
TI  - Early mortality in bone marrow transplantation for acute lymphocytic leukaemia a
      multivariate analysis of risk factors.
AB  - OBJECTIVES: Bone marrow transplantation is still associated with a high case
      fatality rate. This study was conducted to identify the risk factors for early
      mortality in acute lymphocytic leukaemia patients treated with bone marrow
      transplantation. METHODS: Prospectively collected data on 76 acute lymphocytic
      leukaemia patients, treated with 60 mg/kg cyclophosphamide for two consecutive
      days, before (32 patients) or after (44 patients) total body irradiation who
      received an allogeneic (56 patients) or autologous (20 patients) bone marrow
      transplantation were considered in the multivariate analysis including fifteen
      potentially prognostic variables for early mortality. RESULTS: In the entire
      group, patients older than 20 years had a relative risk for early mortality of
      3.96 (95% confidence interval (CI): 1.33-11.76) and those with a Karnofsky Index
      lower than 90% had a relative risk of 5.56 (95% CI: 1.29-25). In the subgroup of
      allogeneic patients, those over 20 years had a relative risk of 5.17 (95% CI:
      1.30-20.6); the relative risk for patients with a Karnofsky index < 90% was 10.55
      (95% CI: 1.55-71.43) and 8.04 (95% CI: 43-45.07) for acute severe graft-versus
      host disease. Among radiation therapy variables only dose-rate showed a trend
      towards better prognosis in patients treated with less than 5 cGy/min.
      CONCLUSIONS: In our patients and within the range of treatment variables studied,
      age, Karnofsky index, and graft-versus-host disease are the most important
      factors related with early mortality.

PMID- 8258027
TI  - Influence of radiotherapy on long-term relapse in clinically non-secreting
      pituitary adenomas. A retrospective study (1970-1988).
AB  - OBJECTIVE: We wished to evaluate the influence of postoperative radiotherapy on
      the incidence of tumour regrowth in non-secreting pituitary adenomas. METHODS:
      The cases of 57 patients with clinically non-secreting pituitary adenomas were
      retained for a retrospective study of long-term disease-free survival out of a
      series of 66 patients treated between 1970 and 1988. Thirty-three patients were
      treated by surgery only (Group A), and twenty-four by surgery followed by
      external radiotherapy (Group B). Disease-free survival curves were calculated
      according to the Kaplan-Meyer method and compared by the Logrank test. The impact
      of some supposed prognostic parameters--such as tumoural volume, macroscopic
      features of invasiveness and quality of surgical resection--on the disease-free
      survival was analyzed according to the Logrank adjusted test. RESULTS: The mean
      follow-up duration was 7.1 +/- 6.2 years, and eleven patients relapsed: nine in
      group A (27.0%) and two in group B (8.3%), with respective free intervals of 6.1
      +/- 5.0 years and 9.6 +/- 2.4 years. Statistical analysis of the disease-free
      survival curves confirmed that this difference was significant (p < 0.01).
      Further analysis of putative risk factors (the importance of extrasellar
      extension and the estimated quality of surgical resection) was attempted, but it
      did not reach statistical significance. CONCLUSIONS: Radiotherapy is effective in
      preventing post-operative regrowth of non-secreting pituitary adenomas. Whether
      it should be systematically proposed or reserved to selected cases remains to be
      evaluated.

PMID- 8258026
TI  - Effect of erythropoietin treatment on tissue oxygenation in patients with severe
      transfusion dependent renal anaemia.
AB  - OBJECTIVES: Severe renal anaemia can now be effectively treated with recombinant
      human erythropoietin (rhEpo). To evaluate muscle tissue oxygenation in patients
      with severe renal anaemia and the effects of an rhEpo treatment, muscle tissue
      oxygen tensions were measured in 9 patients suffering from end stage renal
      disease with severe renal anaemia before and during rhEpo treatment. METHODS:
      Muscle tissue oxygen pressure (method according to Ehrly and Schroeder),
      transcutaneous oxygen pressure (tcpO2) (Radiometer, Copenhagen), haematocrit
      (micro haematocrit method), plasma viscosity (Ostwald capillary viscometer) and
      erythrocyte aggregation (method according to Ehrly and Schmitt) were determined
      before as well as 4, 8, and 24 weeks after onset of treatment with 80 U/kg body
      weight 3 times per week. RESULTS: Muscle tissue pO2 values before treatment were
      markedly diminished when compared with normals and showed a marked increase into
      the normal range parallel to the increase in haematocrit. tcpO2 values were in
      the upper normal range before treatment and did not show significant changes
      during treatment. Erythrocyte aggregation and plasma viscosity did also not show
      significant changes. CONCLUSION: During rhEpo treatment a marked increase of
      muscle tissue pO2 can be found. This increase may be one of the mechanisms
      responsible for the improved well being and physical exercise tolerance in these
      patients due to erythropoietin treatment.

PMID- 8258028
TI  - Acid-base and electrolyte abnormalities in febrile patients with bacteraemia.
AB  - OBJECTIVES: Very commonly febrile patients with bacteraemia develop a variety of
      acid-base and electrolyte disturbances which play a significant role in the
      morbidity and mortality of these patients. This study was undertaken to describe
      the pathogenetic mechanisms of these abnormalities in febrile patients with
      bacteraemia. METHODS: Fifteen febrile patients with bacteraemia, aged 24-62
      years, were studied. In all patients blood cultures revealed Gram-negative rods.
      None of them had septic shock, diabetes mellitus, renal or liver failure and none
      was receiving drugs influencing acid-base balance and electrolyte levels or was a
      heavy alcohol consumer. RESULTS: Nine patients had respiratory alkalosis, which
      was possibly due to bacterial toxins, while the remaining 6 had a wide-gap
      metabolic (lactic) acidosis coexisting with respiratory alkalosis. Hypokalaemia
      was found in four patients and was mainly due to respiratory alkalosis. However,
      kaliuria due to hypomagnesaemia contributed to hypokalaemia in 2 patients.
      Hypomagnesaemia was detected in 3 patients and was attributed to respiratory
      alkalosis as well as to magnesiuria induced by metabolic acidosis or phosphate
      depletion. Hypophosphataemia was found in 5 patients who also had respiratory
      alkalosis and/or phosphaturia due to metabolic acidosis or hypomagnesaemia.
      Finally, one patient had multifactorial origin hypocalcaemia. CONCLUSION: Febrile
      patients with bacteraemia develop a number of acid-base and electrolyte
      disturbances attributed to various pathogenetic mechanisms.

PMID- 8258029
TI  - Relevance of reduced portal flow velocity, low platelet count and enlarged spleen
      diameter in the non-invasive diagnosis of compensated liver cirrhosis.
AB  - OBJECTIVES: The aim of this prospective study was to identify the combination of
      parameters best able to predict the diagnosis of compensated cirrhosis. METHODS:
      One hundred and fourteen patients with suspected chronic compensated liver
      disease were divided, on the basis of bioptical findings, into two groups: group
      A, without cirrhosis (n = 58) and group B, with cirrhosis (n = 56). A number of
      biochemical parameters, the extent of oesophageal varices, spleen size, portal
      vein diameter and maximum and mean portal flow velocity measured by duplex
      Doppler ultrasonography were taken into account in a binary forward-stepwise
      multiple logistic regression analysis. RESULTS: Only three variables were present
      in the final regression equation, maximum portal flow velocity affording the
      highest correlation with the histological diagnosis of cirrhosis (p = 0.0007),
      with an overall predictive value of 87.7%. When associated with the bipolar
      diameter of the spleen (p = 0.0169) and the number of platelets (p = 0.0487), the
      predictive value rose to 94.7%. If all three parameters were normal, a non
      cirrhotic liver disease was most likely (96% probability); if two or three of the
      parameters were abnormal, liver cirrhosis was almost certain (98% probability);
      if only one parameter was abnormal, the clinical diagnosis was uncertain.
      CONCLUSIONS: This study emphasizes the usefulness of duplex Doppler
      ultrasonography in the non-invasive diagnosis of compensated cirrhosis.

PMID- 8258030
TI  - Colonoscopy in the elderly: a study of 200 cases.
AB  - OBJECTIVES: To evaluate tolerance and diagnostic yield of colonoscopy in elderly
      patients. METHODS: We studied retrospectively 200 consecutive colonoscopies
      performed in patients older than 80 years (mean age: 83.5 +/- 3.1). We analyzed
      the following factors: indication, type and tolerance of the preparation,
      analgesia, tolerance of the procedure, information provided by the examination
      and therapeutic consequences. RESULTS: The indications were: anaemia in 81 cases,
      change in bowel habits in 58 cases, rectal bleeding in 26 cases and others in 35
      cases. Preparation (4.2 +/- 1.3 L Polyethylene-glycol) was good 150 times (75%),
      moderate 27 times and poor 23 times. It was tolerated well 122 times (61%) and
      poorly 78 times (39%). Sixty-six colonoscopies were performed without any
      analgesia, diazanalgesia was used in 108 cases, general anesthesia in 8 and
      diazepam and/or antispasmodics in 18. Tolerance of colonoscopy was good in 140
      cases (70%), moderate in 37 cases and poor in 23 cases. Tolerance was better with
      analgesia than without (p < 0.001). The caecum was reached in 167 cases (83.5%).
      Colonoscopy was normal in 68 cases (34%). The lesions discovered were: 40 polyps
      larger than 10 mm, 41 diverticulosis, 29 cancers, 7 ischaemic colitis, 5
      angiodysplasias, 5 sigmoiditis, 3 villous adenomas, 1 Bothriocephalus and 1
      thermometric ulceration. A lesion responsible for the symptoms was diagnosed in
      80 cases (40%). Diagnostic yield was better when indication was anaemia (52%)
      than change in bowel habits (24%) (p < 0.001). The lesions were treated
      endoscopically in 41 cases (38 polypectomies, 3 electrocoagulations) and
      surgically in 22 cases. Colonoscopy as well as its preparation were well
      tolerated in 93 cases (46.5%). CONCLUSION: In a selected elderly population,
      colonoscopy was better tolerated with analgesia; large bowel preparation was
      often difficult. The diagnostic yield was relatively good. A multicentric
      prospective study is underway in order to determine the predictive criterias
      allowing an improvement of colonoscopic yield in the elderly.

PMID- 8258031
TI  - Management of hepatic encephalopathy with oral zinc supplementation: a long-term
      treatment.
AB  - OBJECTIVES: The effect of long-term oral zinc supplementation, in addition to
      standard therapy (protein-restricted diet and lactulose) on recurrent hepatic
      encephalopathy, was assessed in a double-blind study. METHODS: Ninety cirrhotic
      patients with stable recurrent hepatic encephalopathy, after following a one
      month period of standard therapy, were randomized to receive oral zinc acetate
      supplementation (600 mg/day) in addition to standard therapy or to continue only
      standard therapy (a diet containing 0.8 g/kg/day of protein and 90 g/day of
      lactulose) for six months. Psychometric tests, NCT (number correction test) and
      PSE (portal-systemic encephalopathy) Index, were used to evaluate the degree of
      hepatic encephalopathy, both at the beginning and the end of each treatment
      period. RESULTS: Oral zinc supplementation in addition to standard therapy was
      able to normalize serum zinc levels. The patients who never showed clinical signs
      of hepatic encephalopathy during the trial were 88.6% in zinc-group and 86% in
      only standard therapy group. Psychometric tests, NCT and PSE Index, were
      statistically better than basal values either in zinc-group or in only standard
      therapy group. CONCLUSIONS: Final values of psychometric tests were better in
      zinc-group than only standard therapy group but the differences were not
      statistically significant.

PMID- 8258032
TI  - Cytokines: an overview.
AB  - This review is an introduction to cytokines and their involvement in various
      mechanisms of immune defense. These features are then exemplified by reference to
      cytokines in sepsis, malaria, rheumatoid arthritis and schistosomiasis. In so
      doing the different functions of T-helper-1 and T-helper-2 lymphocytes become
      apparent, and how the balance is manipulated by the body in response to
      particular invading agents. Finally the prospect of therapy to reinforce or
      negate particular cytokines is illustrated by examples.

PMID- 8258033
TI  - A model for teaching and assessing ethics and law within the clinical curriculum.

PMID- 8258034
TI  - Do we know enough to introduce semi-automatic defibrillation by ambulancemen in
      Belgium?
AB  - The application of semi-automatic external defibrillators by ambulancemen or
      emergency medical technicians is in the U.S.A. accepted as a substantial progress
      in the treatment of out-of-hospital sudden death. A retrospective estimation of
      the percentage of patients registered by the Belgian Cardio-Pulmonary-Cerebral
      Resuscitation study group between 1983 and 1987 that could benefit from early
      defibrillation yielded a gain in good survival of 1% for the whole population. In
      1991 a prehospital semi automatic external defibrillation program was started as
      a feasibility study in several two-tiered emergency physician staffed systems
      with an ongoing registry of cardiac arrest events. For Bruges and Ghent there was
      a non-significant increase in prolonged survival in the ventricular fibrillation
      subgroups with respectively 4.7% and 5.1% since the introduction of the semi
      automatic external defibrillators. Apparent differences between our emergency
      medical systems and e.g. Seattle, such as the number of 1st tier units covering
      the population and a short delay between 1st and 2nd tier might account for a
      lack of a statistically significant improvement so far.

PMID- 8258035
TI  - Is blood clotting synonymous with thrombosis? Clinical forms of blood
      coagulation.

PMID- 8258036
TI  - Horner's syndrome secondary to benign multinodular goitre with hyperthyroidism.

PMID- 8258037
TI  - Brucella peritonitis in a cirrhotic patient with ascites.

PMID- 8258038
TI  - Polysplenia with congenital short pancreas without other associated
      malformations.

PMID- 8258039
TI  - Alveolar cell carcinoma following treatment of acute non-lymphocytic leukaemia.

PMID- 8258040
TI  - HIV serosurvey in pregnant women in Uganda.

PMID- 8258041
TI  - Liver damage during interferon therapy for chronic myeloid leukaemia.

PMID- 8258042
TI  - Blood lead levels in children admitted to hospitals in Asturias.

PMID- 8258043
TI  - Treatment of multiple myeloma with etidronate: results of a multicentre double
      blind study. Groupe d'Etudes et de Recherches sur le Myelome (GERM).
AB  - OBJECTIVES: Because osteoclastic bone resorption is stimulated in multiple
      myeloma, we evaluated the efficacy of etidronate in this disease, in a
      multicentre controlled study. METHODS: Ninety-four previously untreated patients
      with stage II or III multiple myeloma received, in addition to the same
      chemotherapy, 10 mg/kg/day etidronate per os (n = 49) or placebo (n = 45) for 4
      months. The evaluation was clinical (pain, Karnofsky, survival), biological and
      radiological. Forty-one patients had iliac bone biopsy before the treatment and
      34 patients also at the end of the study. Histologic bone parameters were
      compared with 49 normal controls. RESULTS: No statistical difference was found
      between etidronate and placebo treated patients for clinical, biological and
      radiological parameters. Compared with controls, pretreatment biopsies showed
      markedly increased bone resorption and decreased trabecular bone volume. Bone
      resorption decreased significantly in patients with etidronate compared with
      those with placebo (p < 0.05). CONCLUSION: Though we found no clinical,
      biological and radiological difference with placebo, etidronate inhibited the
      increased bone resorption in multiple myeloma.

PMID- 8258044
TI  - Primary hyperparathyroidism in very old patients.
AB  - OBJECTIVES: To evaluate the clinical presentation and biological features of
      primary hyperparathyroidism (pHPT) in very old subjects. METHODS: Thirty patients
      aged 75 years or more, with pHPT were analyzed retrospectively. The diagnosis of
      pHPT was based on usual biological signs and was always confirmed by the finding
      of morphological abnormalities with parathyroid imaging or neck surgical
      exploration. RESULTS: At initial examination, recent general symptoms and
      neuromuscular symptoms were observed in 87% and 83% of the cases, respectively.
      Neuropsychiatric manifestations were noted in 73% of the cases. Confusion and
      depression were the most frequent findings, observed in 30% and 27% of the cases,
      respectively. In one of two patients with dementia like state, the mental status
      improved dramatically after surgery of the parathyroid adenoma. Serum calcium
      levels were in the normal range in 13% of the cases and equal or below 110 mg/L
      in 47% of the cases. There was no correlation between serum calcium level and the
      severity of mental changes. Serum parathyroid hormone determinations were
      abnormal in 93% of the patients. Thirteen patients underwent surgery with
      biological improvement in all cases. An ultrasonically guided percutaneous
      ethanol injection of parathyroid adenoma was performed in 10 patients with a
      biological cure rate of 50%. CONCLUSION: This study shows the major prevalence
      and potential severity of neuropsychiatric disorders in pHPT in very old
      patients. Because neuropsychiatric disturbances can respond favourably to
      surgical treatment, the clinician must systematically look for pHPT in elderly
      patients with cognitive impairment.

PMID- 8258045
TI  - Acquired cystic kidney disease in renal insufficiency: a multicentre study. Group
      of Nephrologists of the East of France.
AB  - OBJECTIVES: A cross-sectional study was undertaken in order to a) investigate the
      prevalence of acquired cystic kidney disease and the prevalence of associated
      cancer; b) evaluate the best diagnostic procedure; c) look for a possible
      relationship with improvement of anaemia. METHODS: All patients treated in 10
      Dialysis Centres in the East of France, except those with polycystic kidney
      disease, were examined during the same 6-month period by echography and computed
      tomography scanning, when they were at initiation of dialysis (T0) or when they
      reached exactly 5 years (T5), 10 years (T10), 15 years or more (T15) of dialysis.
      RESULTS: One hundred sixty-one patients were evaluated: 50 at T0, 48 at T5, 33 at
      T10 and 30 at T15. CONCLUSION: a) Prevalence of acquired cystic kidney disease
      was 57.2%, ranging from 30% at T0 to 83.3% at T15; prevalence of associated
      cancer was 1.1%; b) computed tomography was the best diagnostic procedure, but
      when compared with it, echography had a sensibility of 0.88 and a specificity of
      1; c) only in patients with large-sized cystic kidneys, there was an improvement
      of anaemia.

PMID- 8258046
TI  - Mild liver abnormalities associated with elevated plasma factor VII and protein C
      in hypertriglyceridaemic patients.
AB  - OBJECTIVES: It is now well established that not only atheroma, but also
      thrombosis play a key role in coronary heart disease. High levels of some
      haemostatic parameters, which increase the risk of thrombosis, are often
      associated with lipid abnormalities. The mechanism by which patients with
      hyperlipidaemia display an increase in some haemostatic parameters remains to be
      established. Therefore, in this study, we measured factor VII antigen and its
      clotting activity as well as protein C-activity in a population of patients who
      had been referred to us for hyperlipidaemia. METHODS: We carefully selected a
      population of 130 healthy asymptomatic males. The study population consisted of
      patients aged 45.5 +/- 12.3 years with mean (+/- SD) levels of cholesterol and
      triglycerides of 2.60 +/- 0.58 g/L and 1.82 +/- 1.95 g/L, respectively. RESULTS:
      We found higher levels of plasma factor VII activity, antigen and protein C
      activity in patients displaying hypertriglyceridaemia. In a univariate analysis
      there was a significant and positive correlation between these coagulating
      factors and the hepatic enzymes. In a multivariate analysis the three parameters
      which could significantly account for the variation of factor VII antigen were
      age, hepatic enzyme and triglyceride concentrations whereas only triglyceride
      levels were associated with factor VII activity; The parameters associated with
      protein C levels were the concentration of the hepatic enzymes and the levels of
      serum triglycerides. CONCLUSIONS: We suggest that mild liver abnormalities such
      as steatosis may be one of the factors which can lead to an increase in factor
      VII and protein C levels.

PMID- 8258047
TI  - Spontaneous dissection of the internal carotid artery in 68 patients.
AB  - OBJECTIVES: Our purpose was to know more about the symptoms and clinical and
      radiological outcome of spontaneous dissections of the internal carotid artery in
      a retrospective study of 68 patients aged 20 to 71 (mean 46). METHODS: The
      diagnosis of dissection was based on angiographic findings. Nine percent of
      patients had minor symptoms such as a subjective bruit or painful Horner's
      syndrome, without an ischaemic event. Cerebral ischaemia was present in 90% of
      cases and occurred within a month of the initial event in all cases but one and
      was the first symptom in 53% of cases. RESULTS: Magnetic resonance imaging
      performed in 21 cases showed haemorrhage in the vessel wall. Resolution of the
      angiographic appearances occurred in 65% of cases after 3 months. In cases of
      stroke, more than half of the patients had poor functional outcome, factors
      conveying poor prognosis were massive stroke, embolic mechanism and lack of local
      recanalization. CONCLUSION: Spontaneous dissection of the internal carotid artery
      is not a rare cause of cerebral ischaemia and can present with minor symptoms
      without an ischaemic event. Doppler ultrasonography and magnetic resonance
      imagery are helpful in diagnosis and follow-up.

PMID- 8258048
TI  - Free and decomplexed human immunodeficiency virus p24 antigenaemia in black
      patients with AIDS and AIDS-related disorders.
AB  - OBJECTIVES: To determine the clinical signification of free and decomplexed p24
      antigenaemia in HIV1-infected black individuals. PATIENTS AND METHODS: Sixty
      African patients with pre-AIDS (n = 12) and AIDS (n = 48), hospitalized in the
      Centre National Hospitalier Universitaire de Bangui, Central African Republic,
      were prospectively included. 15 HIV1-seronegative healthy African subjects served
      as controls. Serum p24 antigenaemia was detected using a polyclonal and a
      monoclonal sandwich enzyme immunoassay (EIA). All sera were tested again after
      acid pretreatment (45 mn incubation of serum with a 0.5 N solution of HCl at +37
      degrees C). RESULTS: The polyclonal EIA and the monoclonal EIA detected
      respectively four (7%) to six (10%) free p24 antigen positive samples from the
      HIV1-infected individuals, with a similar frequency in pre-AIDS and AIDS
      patients. None of the controls were found p24 antigen positive. After acid
      pretreatment, the rate of detectable p24 antigenaemia increased significantly,
      leading with the monoclonal EIA to a 47% positivity rate (p < 0.001), and the
      patients with AIDS became more frequently p24 antigen positive (54%), than the
      patients with pre-AIDS (17%) (p = 0.02). CONCLUSION: Detectable p24 antigenaemia
      in HIV1-infected African subjects could be obtained in nearly half of cases by
      increasing the sensitivity of the assay using monoclonal EIA and acid hydrolysis
      of circulating immune complexes. Decomplexed p24 antigenaemia in HIV1-infected
      Black African patients could have predictive signification similar to free p24
      antigenaemia in Caucasians.

PMID- 8258049
TI  - Direct isotopic assessment of aerosolized pentamidine deposition: influence of
      nebuliser.
AB  - OBJECTIVES: The aim of the present study was to compare the efficiency of
      pulmonary deposition of pentamidine using the Respirgard II jet nebuliser or the
      Fison ultrasonic nebuliser with 99m technetium (99m Tc) labelled pentamidine in
      the current conditions of recommended treatment. The study was designed in three
      stages, to verify particle size distribution, to validate the isotope labelling,
      and to compare pulmonary deposition of pentamidine isethionate with the two
      nebulisers. METHODS: Count median aerodynamic diameter and mass median
      aerodynamic diameter were measured using the velocimetry technique and aerosol
      dispersion was calculated according to the standard deviation defined by the
      ratio of diameters between 84.3% and 50% of the total distribution. Stability of
      labelling was checked both in vitro, by radiochromatography, and in vivo, by the
      absence of free technetium thyroid fixation after intravenous injection of the
      preparation to a rat and inhalation by baboons. The direct isotopic technique was
      used to compare pulmonary deposition of 300 mg aerosolized 99m Tc labelled
      pentamidine isothionate with the two nebulisers in four HIV patients treated with
      primary prophylaxis. RESULTS: Count median aerodynamic diameter and mass median
      aerodynamic diameter (MMAD) were higher with Fisoneb than with Respirgard II.
      Nevertheless Fisoneb MMAD remained in the optimal range for peripheral
      deposition. In one patient, pentamidine lung burden was higher using the
      Respirgard II (13% of dose originally in nebuliser) when compared with the
      Fisoneb (10.2% of dose originally in nebuliser). A better result was obtained in
      the 3 other patients with Fisoneb (mean = 14.3%) compared with Respirgard II
      (mean = 3.8%). In all 4 patients gastric contamination was higher with Fisoneb
      (mean = 5.2%) as compared with Respirgard II (mean = 2.6%). Cough and
      bronchospasm were not observed with either device. CONCLUSION: This study showed
      that Fisoneb, a practical and cheap nebuliser which has proved to be effective in
      clinical studies when used for pentamidine nebulisation, leads to correct
      particle size distribution and pulmonary deposition of the drug. We believe that
      such studies to evaluate aerosol characteristics should be recommended for any
      kind of nebuliser.

PMID- 8258050
TI  - Early social intervention in the emergency department.
AB  - OBJECTIVES: To assess the usefulness of an early medical social intervention
      conducted by a specially oriented medical social workers stationed in the
      Emergency Department. METHODS: Prospective study during a 2-month reference
      period, in a 900-bed inner-city teaching hospital that has approximatively 30,000
      emergency department visits annually, providing health care facilities for a
      metropolitan area with a population of 230,000. RESULTS: Among 6,000 patients
      presenting to the emergency department during the study, 72 were found to require
      social intervention (1.2% of all emergency department visits, 6.85% of admissions
      to the hospital). Social intervention consisted of telephone calls (89%),
      correspondence by letters (26.5%), counsel and advice (23.5%), out-hospital
      intervention (14%) and resulted in: house-keeping help (34.5%) or transferal to
      nursing homes or nursing hospitals (28%) of elderly patients; aid to homeless and
      socially disadvantaged people, such as transferal to homing city shelters,
      clothing supply, etc., allowing extra hospital maintenance (23.5%);
      regularization of health insurance affiliation (10%); aid in various other social
      situations (22%). CONCLUSION: An early medical social intervention in the
      emergency department resulted in alternatives to hospital admission for a high
      proportion of patients (82%).

PMID- 8258051
TI  - Isolated systolic hypertension in the elderly subject.
AB  - Interest in isolated systolic hypertension in the elderly has increased in the
      last few years. The definition of this disorder remains controversial: according
      to most authors, the systolic blood pressure has to be above 160 mm Hg and the
      diastolic under 90 mm Hg. The prevalence depends on number of visits, as well as
      on sex, age and race. The elderly is characterized by haemodynamic and
      neurohormonal features, which have to be pointed out: cardiac output and renal
      blood flow as well as hepatic blood flow are significantly lower than those of
      younger adults; great vessels compliance is diminished, baroreflex is impaired
      and cerebral autoregulation curve is shifted towards the right. From a prognostic
      point of view, systolic hypertension is now recognized as an independent risk
      factor for cardio-vascular morbidity and mortality. Recently, the SHEP study has
      demonstrated that the treatment of isolated systolic hypertension with diuretics
      alone or associated with beta-blockers resulted in a significant reduction in the
      incidence of stroke and major cardio-vascular events. The effectiveness of
      angiotensin-converting enzyme inhibitors and calcium antagonists is still under
      evaluation.

PMID- 8258052
TI  - A diagnostic dilemma: Wegener's granulomatosis, relapsing polychondritis or both?

PMID- 8258053
TI  - Choriocarcinoma and endocrine paraneoplastic syndromes.

PMID- 8258054
TI  - Panniculitis and myelodysplasia: report of 2 cases.

PMID- 8258055
TI  - Reactive polyarthritis induced by intravesical BCG therapy for carcinoma of the
      bladder.

PMID- 8258056
TI  - Isolated pseudotumoural sarcoidosis of the hypothalamic-pituitary area.

PMID- 8258057
TI  - Severe hyperkaliaemia induced by a non-cardioselective beta-adrenergic blocker
      and pheochromocytoma in a normotensive patient.

PMID- 8258058
TI  - Primary involvement of the heart in Hodgkin's disease: prolonged survival in a
      patient.

PMID- 8258059
TI  - Pulmonary Mycobacterium avium intracellulare with transient CD4+ T
      lymphocytopenia without HIV infection.

PMID- 8258060
TI  - Complete resolution of spinal epidural abscess with short medical treatment
      alone.

PMID- 8258061
TI  - Crystalluria prevalence in elderly.

PMID- 8258062
TI  - Reduction of HIV transmission during laparoscopic procedures.

PMID- 8258063
TI  - Open laparoscopic cholecystectomy in pregnancy.
AB  - Since the introduction of laparoscopic cholecystectomy in 1989, surgeons
      worldwide have become familiar with the basic techniques involved. Pregnancy has
      previously been considered an absolute contraindication to laparoscopic
      cholecystectomy; however, we present three cases of laparoscopic cholecystectomy
      in pregnancy. If conservative management fails, this method, far from being
      absolutely contraindicated, should be the procedure of choice in pregnancy, as it
      has already become in nonpregnant patients. Transvaginal ultrasound allows
      continuous monitoring of fetal heart rate in all stages of pregnancy after the
      7th week. The open (Hasson) technique should be strongly considered if accidental
      uterine puncture and potential fetal damage are to be avoided.

PMID- 8258064
TI  - Safe laparoscopic cholecystectomy without intraoperative cholangiography.
AB  - The role of intraoperative cholangiography during laparoscopic cholecystectomy is
      controversial. Between July 1990 and June 1991, 82 of 84 consecutive patients
      (mean age, 46 +/- 14 years) with symptomatic cholelithiasis successfully
      underwent laparoscopic cholecystectomy with only one intraoperative
      cholangiogram. Fourteen patients underwent preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) for suspected choledocholithiasis of which two
      demonstrated common duct stones and underwent sphincterotomy. Complications of
      laparoscopic cholecystectomy included one each of bilioma, umbilical wound
      infection, epigastric trocar site hernia, and flank seroma. No major bile duct or
      vascular injury occurred. Follow-up data was available on all patients for a mean
      of 7.4 months (range, 3-13 months). Three patients developed symptoms suggestive
      of biliary tract disease at 0.25, 4, and 8 months postoperatively. Symptoms
      spontaneously resolved in all three; all underwent ERCP, of which two were normal
      and one unsuccessful. We have concluded that (a) a meticulous operative
      dissection resulted in no major bile duct or vascular injury; (b) patients with
      unsuspected choledocholithiasis preoperatively rarely developed postoperative
      symptoms; and (c) the practice of laparoscopic cholecystectomy can be conducted
      safely without intraoperative cholangiography.

PMID- 8258065
TI  - Reduction of HIV transmission during laparoscopic procedures.
AB  - Laparoscopic surgery has recently been encouraged as an alternative to open
      procedures in patients infected with the human immunodeficiency virus (HIV). The
      laparoscopic technique reduces exposure to blood products and sharp instruments;
      however, it exposes the surgical team to the HIV-infected patient in a manner not
      encountered during open procedures. The evacuation of the pneumoperitoneum during
      laparoscopic procedures releases aerosolized HIV-infected blood and peritoneal
      fluid into the operative suite. Evacuation of the penumoperitoneum into a closed
      system and appropriate precautions during instrument changes will diminish the
      exposure of the surgical team to aerosolized HIV-infected blood and peritoneal
      fluid.

PMID- 8258066
TI  - Introduction of laparoscopic techniques in gastrointestinal surgery: experience
      at a Norwegian university hospital as revealed by prospective comparative
      studies.
AB  - Prospective studies compared (a) laparoscopic and open cholecystectomy and (b)
      laparoscopic and open appendectomy. A second purpose of this study was to assess
      the value of laparoscopic staging of pancreatic and liver tumors. A total of 141
      cholecystectomy cases were studied, comprising a laparoscopic group (n = 50), an
      open prospective control group (n = 50), and historical controls (n = 41). The
      need for postoperative analgesics was significantly reduced with the laparoscopic
      procedure compared with open cholecystectomy. Hospital stay was 1 (1-5) day after
      laparoscopic cholecystectomy versus 6 (5-28) days after open cholecystectomy.
      Time away from work was 9 (4-21) versus 28 (21-60) days. These differences were
      statistically significant (p < 0.001). Complication rates were 8% in both
      prospective groups. A similar comparative study of laparoscopic appendectomy
      versus the open technique was undertaken, with 10 patients in each prospective
      group. Again, hospital stay and time away from work proved shorter for
      laparoscopic procedures. Finally, 15 staging procedures for pancreatic and liver
      cancers were performed. One patient with unresectable liver metastases was spared
      explorative laparotomy.

PMID- 8258067
TI  - Multi-institutional survey of laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy (LC) is being used more frequently in patients
      undergoing gallbladder removal. Most initial studies have centered on the limited
      experience of a few select surgeons or institutions and may not accurately
      reflect the current state of LC. We used written and telephone survey tools to
      103 community hospitals in Michigan to identify the utilization of LC, the
      criteria for training and credentialing, and patient outcome. Of 103 hospitals,
      75 (73%) were involved with LC and 56% of these had < 100 beds. We found a large
      variation in the indications, contraindications, equipment, methods, and
      credentialing criteria. Major complications, including some not previously
      reported, were identified and occurred more frequently than previously described.
      LC is being widely applied and the majority of hospitals have < 100 beds. LC may
      carry higher risks than previously reported. Collected series and registry data
      that include community hospital experiences should better delineate the outcome
      of LC.

PMID- 8258068
TI  - Laparoscopic hernia repair: use of a fenestrated PTFE graft with endo-clips.
AB  - A prospective study of 15 patients undergoing elective laparoscopic herniorrhaphy
      was performed using the introduction of a polytetrafluorethylene (PTFE, GORE-TEX)
      patch fenestrated around the edges to facilitate the use of an Endo-Clip applier.
      Patient tolerance was increased, and time lost from work was reduced. Two
      patients treated for prostatitis resumed sexual activity within the first 10 days
      with no recurrences or intra-abdominal infections. Fenestration of the PTFE patch
      was possible without fraying the material and without compromising the strength
      of the patch. The Endo-Clip applier secures the patch to the ligamentous
      structures. Initial cases were followed for 6 months.

PMID- 8258069
TI  - Laparoscopic repair of incisional abdominal hernias using expanded
      polytetrafluoroethylene: preliminary findings.
AB  - Laparoscopic techniques were used in five cases to repair incisional abdominal
      hernias ranging in size from 1.5 to 6 cm2. Four to five trocars were used in each
      case, one in the upper midline and three or four placed laterally. All repairs
      were made using 1-mm-thick expanded polytetrafluoroethylene patches inserted
      intraperitoneally and stapled to the anterior abdominal wall over the defects,
      making use of intra-abdominal pressure to secure the repair. The surgical
      technique is an extension of our current laparoscopic techniques for repairing
      inguinal hernias and potentially offers a significant decrease in morbidity.

PMID- 8258070
TI  - Techniques of pneumoperitoneum.
AB  - Laparoscopic cholecystectomy has become the standard of care for symptomatic
      gallstone disease. One of the key steps in the procedure is to obtain
      pneumoperitoneum and insert the first trocar safely through the umbilicus. In our
      first 150 laparoscopic cholecystectomies, the pneumoperitoneum was obtained by
      inserting a Veress needle through the umbilicus, followed by blind insertion of
      the first trocar through the umbilicus. This was associated with several
      complications, including bowel laceration. Subsequently, we adopted the open
      laparoscopic technique described by Hasson in 1974. Using this, we have performed
      150 laparoscopic procedures without complications. In this article, we compare
      and analyze the results and complications of both techniques. We find open
      laparoscopy to be a quicker, safer, and superior technique for obtaining
      pneumoperitoneum as well as a more cost-effective procedure.

PMID- 8258072
TI  - A method for controlling bleeding from abdominal wall puncture site after
      laparoscopic surgery.
AB  - Bleeding from puncture sites can complicate laparoscopic procedures. Although it
      is usually self-limited, bleeding can persist into the postoperative course or
      obscure the field during the operative procedure. The following article describes
      a simple method for controlling this type of bleeding. To date, it has been used
      successfully on two separate occasions.

PMID- 8258071
TI  - Coelioscopic cholecystectomy: experience with 201 initial patients.
AB  - Over a 20-month period, 201 patients underwent laparoscopic cholecystectomy,
      including 159 women and 42 men (mean age, 44.2 years). Indications included
      symptomatic cholelithiasis (181 cases), acute cholecystitis (15 cases), gallstone
      pancreatitis (two cases), and cholangitis (three cases). Mean operating time was
      78 min. Overall conversion rate was 5.4% (11 cases). Conversion to open procedure
      was elective in nine patients and enforced in two because of uncontrollable
      bleeding from the cystic artery. Three of the former nine patients who were
      converted subsequently had acute cholecystitis. One case of cellulitis at the
      umbilical stab wound and one case of bile leak, which drained spontaneously,
      occurred in patients operated on for acute cholecystitis. Laparotomy was
      performed on the 7th postoperative day for a liver bed hemorrhage in a patient
      presenting with cholecystitis. One common bile duct injury occurred in a patient
      with cholecystitis necessitating a biliary reconstruction. No perioperative
      deaths occurred. Mean hospital stay was 3.4 days. Despite several advantages,
      laparoscopic cholecystectomy must be performed by surgeons experienced in biliary
      tract surgery.

PMID- 8258073
TI  - Laparoscopic cholecystectomy. A prospective analysis of the potential causes of
      failure.
AB  - Most experienced laparoscopic units suggest a rate of conversion to open
      cholecystectomy of about 5%. Some failures are predictable preoperatively. We
      have reviewed the prospective data collected on our first 285 laparoscopic
      cholecystectomies to provide a basis for advising patients about the likelihood
      of conversion (failure) if laparoscopic cholecystectomy is attempted. Risk factor
      analysis was performed to assess the effect on the conversion rate of clinical
      presentation, preoperative ultrasound features, previous abdominal surgery, and
      morbid obesity. The overall conversion rate was 4.9%. We identified three
      preoperative clinical parameters associated with a high risk of failure at
      laparoscopic cholecystectomy: a contracted gallbladder on ultrasound, gallstone
      pancreatitis, and a previous history of upper abdominal surgery. Factors that did
      not predict failure were: an ultrasound report of a thick gallbladder wall,
      morbid obesity, or acute cholecystitis. It is concluded that laparoscopic
      cholecystectomy is technically feasible in most patients, but those having the
      above-mentioned risk factors should be warned of a higher than usual chance of
      conversion to open cholecystectomy.

PMID- 8258074
TI  - Endoscopic management of the difficult common bile duct stone.
AB  - Over the past two decades, endoscopic sphincterotomy has become the primary
      therapy for retained or recurrent choledocholithiasis. Nevertheless, in about 10%
      of patients, complete ductal clearance is not possible using standard balloon and
      basket techniques. A variety of endoscopically guided lithotripsy devices can
      substantially improve the chances of extracting stones that are resistant to
      conventional methods. Fiberoptic technology has advanced to the point where these
      procedures can be performed under direct vision through ultrathin fiberscopes.
      This paper examines the current experience with these intracorporeal techniques
      for the difficult common bile duct stone.

PMID- 8258075
TI  - Laparoscopic small bowel resection and anastomosis.
AB  - Our aim was to assess the feasibility and safety of performing totally
      intracorporeal laparoscopic small bowel resection and anastomosis using a linear
      stapling device. Laparoscopic small bowel resection and anastomosis were
      performed in five young domestic pigs. Five trocars were used (2-5 mm, 2-11 mm,
      and 1-12 mm) for video laparoscopic access to the peritoneal cavity. Segments of
      jejunum 5 to 10 cm long were excised using two firings of a 30-mm linear stapler
      (Endo-GIA). The bowel was anastomosed with the stapler in a functional end-to-end
      fashion, and the enterotomy was stapled closed. The excised bowel segment was
      then placed in a nylon entrapment sack, morcellated, and aspirated with an
      automatic electrical tissue morcellator. The pigs recovered uneventfully, were
      allowed oral feedings on the day after the operation, and gained weight normally
      in the postoperative period. Sacrifice after 4 to 10 weeks revealed few
      adhesions, no evidence of anastomotic leaks, and the anastomoses to be widely
      patent. Clinical application will be facilitated by the use of longer
      laparoscopic staplers, but surgeons must also develop suturing skills to assure
      safe performance of advanced laparoscopic surgery.

PMID- 8258076
TI  - Retroperitoneal laparoscopic renal biopsy.
AB  - We describe a technique for renal biopsy using laparoscopic guidance.
      Retroperitoneal laparoscopic dissection and exposure is facilitated by a simple
      balloon-expanding device made of a rubber glove tied around a catheter.
      Laparoscopic renal biopsy is associated with less morbidity than open renal
      biopsy and is ideal when percutaneous renal biopsy is contraindicated or is not
      feasible.

PMID- 8258077
TI  - Laparoscopic closure of gastric stab wounds: a case report.
AB  - For years laparoscopy has been used selectively in the diagnosis of blunt and
      penetrating injuries to the abdomen. Recent advances in instrumentation have
      taken laparoscopy beyond its limited role in diagnosis. Use of the laparoscope
      for therapeutic intervention in selected cases of abdominal trauma is now
      possible. Here we report the use of laparoscopic techniques to diagnose and treat
      two stab wounds to the anterior wall of the stomach.

PMID- 8258078
TI  - Laparoscopic cholecystectomy for gallbladder ascariasis.
AB  - A case is presented of persistent gallbladder infestation by Ascaris lumbricoides
      that was successfully treated by laparoscopic cholecystectomy. The management of
      this rare manifestation of ascariasis is reviewed.

PMID- 8258080
TI  - [The blood scandal is presently playing a fundamental role in French society].

PMID- 8258079
TI  - Laparoscopic colostomy closure.
AB  - Perforated sigmoid diverticulitis often results in the patient undergoing a
      sigmoid resection, closure of the rectal stump, and an end sigmoid colostomy. To
      reestablish intestinal continuity, the patient must undergo a second major intra
      abdominal operation. We have developed a technique of laparoscopic colostomy
      closure to reestablish intestinal continuity and have used it in two patients.
      Because of the reduced operative pain and shorter recovery period, this minimally
      invasive technique would be a better surgical alternative to colostomy closure.

PMID- 8258081
TI  - [Working conditions of operating room personnel. Different symptoms observed and
      pregnancy outcome].
AB  - Neuropsychological symptoms and tiredness were reported more frequently by
      workers in less often scavenged theatres than by controls. The rate of
      spontaneous abortions was higher among pregnancies for which women were working
      in operating theatres.

PMID- 8258082
TI  - [A traditional anesthesia consultation or a "telephone interview" within the
      framework of ambulatory surgery?].
AB  - Preoperative assessment for anaesthesia must detect in the setting of ambulatory
      surgery both medical and sociopsychologic problems which may contraindicate the
      ambulatory aspect of the procedure. The goal of our prospective study was to
      assess the efficacy of a preoperative telephone interview in screening the
      medical and sociopsychologic problems of ambulatory patients. 1,000 consenting
      consecutive outpatients participated to the study and were randomly allocated to
      one of two groups: patients in the standard group (STD) had a consultation a few
      days before surgery whereas those in the telephonic group (TEL) called the
      anesthetist a few days before, the physical exam being performed on the day of
      surgery. The cancellation of the ambulatory procedure was decided upon either
      medical criterias (MC) or sociopsychologic criterias (from Waetchler). RESULTS:
      both groups were comparable regarding SPC and MC but prescription of preoperative
      tests was more frequent in the STD group (result statistically significant). In
      conclusion, this new approach is as reliable as the standard consultation in
      screening the SPC which remain the most frequent cause of cancellation in
      ambulatory surgery. Therefore this telephonic interview which is simple and
      reliable for screening outpatients may represent a suitable alternative to a
      standard consultation.

PMID- 8258083
TI  - [Management of the terminal phase in the life of a child].

PMID- 8258084
TI  - [Alprazolam as premedication in ophthalmologic surgery].
AB  - Oral premedication with alprazolam was studied in 83 patients before eye surgery.
      Alprazolam appears to be an excellent anxiolytic drug, with minor cardiovascular
      and respiratory side effects. A double blind study should be carried on to assess
      these properties.

PMID- 8258085
TI  - [Transcutaneous electric stimulation of the brain: a comparative study of the
      effects of its combination with peridural anesthesia using bupivacaine-fentanyl
      during obstetrical analgesia].
AB  - In order to test the effectiveness of Anesthelec (transcutaneous cranial
      electrical stimulation with Limoge currents) during labour and delivery, a
      randomized study was carried out in 120 primiparous women with extradural
      anaesthesia during active labor. Combination of transcutaneous cranial electrical
      stimulation with epidural bupivacaine administration has been showed to provide a
      20% pain relief prolongation of the first bupivacaine injection. Statistical
      studies of drug requirement during labor, of cervical dilatation duration, of
      mode and duration of delivery and of analgesia quality showed no beneficial
      additive effect of electrical stimulation for obstetrical analgesia when
      extradural anaesthesia is performed.

PMID- 8258086
TI  - [Anesthesia in ambulatory vascular surgery. Our experience in private practice].
AB  - Outpatient vascular surgery is now widely performed in our clinic of only 50
      beds. It concerns almost exclusively varicose veins stripping. Almost all
      anaesthetic drugs and techniques were used during the period considered,
      excepting spinal anaesthesia and lower limb regional blocks. According to our
      experience, more than anaesthetic techniques, information of the patients and
      security measures govern a successful outpatient practice.

PMID- 8258087
TI  - [Instrumental treatment of an acute renal failure aboard a hospital ship].

PMID- 8258088
TI  - [Which preoperative tests in ambulatory surgery?].
AB  - Anaesthesia for ambulatory surgery implies a strict selection of patients.
      Screening tests are non specific, compared to these ordered for in-patients.
      However, detailed preoperative evaluation is mandatory for ambulatory care to
      function correctly. Many studies conclude that 60% of routine screening tests are
      of no value: no proven benefit in either anaesthetic management or in the
      detection of pathologies which might interfere with anaesthesia has been shown
      with systematic preoperative examinations in asymptomatic subjects (adults or
      children). The detection of an asymptomatic anomaly by routine testing is
      extremely infrequent and does not lead to changes in the operating schedule or in
      the outcome of anaesthesia. Clinical examination and patient history are the only
      predictive elements, so systematic complementary tests should be abandoned and
      replaced by judicious selective prescription.

PMID- 8258089
TI  - [A severe obstruction of the upper airways in a child: procedure to follow].
AB  - We report the case of a tracheal stenosis in a young child as a result of
      prolonged intubation. The anesthetic management of the airway laser surgery is
      discussed. A multidisciplinary cooperation allowed good results.

PMID- 8258090
TI  - [Usefulness of the laryngeal mask in a case of difficult intubation].

PMID- 8258091
TI  - [Induction of labor with peridural anesthesia].
AB  - Epidural anaesthesia for elective induction of labour allows a better planning
      with many advantages for the medical team. A retrospective study was carried out
      to know the opinion parturients who benefited from this technique. This induction
      of labour, though appearing to a slight extent unnatural, is well accepted by the
      parturients. The reasons of satisfaction are mainly the security of childbirth,
      but also a better family organization.

PMID- 8258092
TI  - [Use of a pediatric anesthesia questionnaire. A retrospective study of 17,000
      cases].

PMID- 8258093
TI  - [Problems arising by the creation of an independent ambulatory surgery unit].
AB  - A day case surgery unit offers unquestionable benefits to patients reluctant to
      hospitalization. Also this practice may contribute to reduce septic risks.
      However starting it requires clearly defined basis and a very strict selection of
      patients and procedures. It needs a perfect organization and adapted premises, as
      well as a thorough collective reflection about patients deep motivations and the
      whole team ability to accept such constraining activities.

PMID- 8258094
TI  - [A prospective study of pediatric anesthesia and complications observed in Italy
      over a period of 18 months (January 1990-June 1992)].

PMID- 8258095
TI  - [A strategy for autologous transfusion and total hip prostheses].

PMID- 8258096
TI  - [Serturner and the discovery of morphine].

PMID- 8258097
TI  - [Prevention and control of viral hepatitis].

PMID- 8258098
TI  - [Hepatitis B X antigen binding to p53 protein in the pathogenesis of primary
      hepatocellular carcinoma].
AB  - Much evidences have showed a close relation between HBV infection and the
      development of primary hepatocellular carcinoma (PHC). Molecular genetic study
      showed loss of heterozygosity in PHC and that point mutation of p53 exon 7 at
      codon 249 was important to PHC. But these changes of PHC associated with
      aflatoxin B1 and HBV were not apparent. Thirteen cases of PHC were examined to
      determine whether there were any relationship between HBxAg and p53 protein. HBV
      DNA was integrated to PHC tissue in 9 of the 13 cases by southern blot; HBsAg,
      HBxAg or HBcAg was found in 8 by immunohistochemical staining. None had the point
      mutation of p53 exon 7 at codon 229, 247 and 249 by PCR and restriction enzymes.
      Immunoprecipitation analyses were carried out to test whether anti-X antibody was
      capable of precipitating p53 or anti-p53 could immunoprecipitate HBxAg
      polypeptides from HBV infected tissue. Specific band was detected at 53,000 in 7
      of the 13 cases as precipitating with anti-HBxAg and western blotting using anti
      p53, and specific band was detected at 13,000, 17,000 or 28,000 in 6 of the 13
      cases as precipitating with anti-p53 and western blotting using anti-HBxAg. These
      results revealed that the binding of HBxAg to p53 may be analogous to that
      observed in tumor antigen encoded from selected papovaviruses, and adenoviruses,
      and may be a crucial step in the development of PHC among most HBV infected
      patients.

PMID- 8258099
TI  - [Distribution of hepatitis B virus in testicle tissue in patients with hepatitis
      B infection].
AB  - To study distribution of HBV in the testicle tissue, we used polyclonal antibody
      and ABC method in detecting autopsy testicle in 34 cases. The positive rate of
      HBsAg and HBcAg was 52.9% and 11.8% respectively. The positive cells of
      spermatogonium, primary spermatocytes, spermatid and sertoli cells were single or
      grouped in clusters form in the seminiferous tubule. Of the 6 cases studied with
      in situ hybridization, 2 had HBV DNA in spermatogenic cells in individual
      nucleus. The findings support morphologically the transmission of HBV via sexual
      contact.

PMID- 8258100
TI  - [Molecular cloning and sequencing of hepatitis C virus gene from human blood].
AB  - To clone and characterize hepatitis C virus strain in China, we extracted RNA
      from the pooled plasma of persons with HCV infection in Hunan, China. HCV gene
      was amplified and cloned by RT-PCR and gene recombinant techniques. A total of
      2,307 nucleotides of the complementary DNA clones of HCV (HCV-Hun), including the
      clone of 5' noncoding region (311bp), core region (340bp), envelope region
      (397bp), NS1 region (634bp), NS3 region (245bp), and NS5 region (380bp) were
      isolated and identified. The homologies in nucleotide sequence between HCV-Hun
      and HCV-US or HCV-J were 98.1% and 98.7% respectively in 5' noncoding region;
      92.6% and 97.4% in core region; 74.3% and 88.7% in envelope region; 83.5% and
      91.0% in NS1 region; 82.9% and 94.7% in NS3 region; and 74.8% and 90.1% in NS5
      region. The similar results were seen in deduced amino acid sequence homologies
      between above HCV stains. These findings indicate that HCV-Hun were more mimic to
      HCV-J than HCV-US, and there were considerable heterogeneity in hepatitis C virus
      genomes isolated from different areas of the world.

PMID- 8258101
TI  - [Hereditable characteristics of attenuated live hepatitis A virus H2 strain].
AB  - The toxicity of attenuated hepatitis A virus H2 strain was not increased in
      testing KMB 17 cells of 5 consecutive generations of monkeys at 36 degrees C.
      After injection of attenuated live hepatitis A virus H2 strain in humans, no
      abnormality was noted. Serum hepatitis A antigen was positive after 38 children
      aged 3-9 years were given oral 10(6.5) TCKD50, whereas it was 100% positive in
      the group of same age after percutaneous vaccination. Noninfection of oral
      administration is an important hereditable characteristic differentiation from
      wild strains.

PMID- 8258102
TI  - [Mapping of the transforming gene by fluorescence in situ hybridization].
AB  - A transforming gene of human nasopharyngeal carcinoma was cloned from Chinese
      nasopharyngeal carcinoma cell line CNE2. This gene was different from a number of
      known oncogenes as was reported previously. The NPC transforming gene was 16kb in
      size, and the Alu negative 2.8kb fragment was cloned into pSP70 plasmid.
      Linearized Tx pSP70 recombinant plasmid was nick translated in the presence of
      biotin-11-dUTP, incubated with an excess of sonicated human DNA, and used as a
      probe for fluorescence in situ hybridization. Signals of hybridization were
      detected by successive treatments with FITC-labeled avidin. 57% of grains were
      located on chromosome 8; 51.8% of them were mapped to the 8q23-->8q24.1 region of
      chromosome 8's. The Tx gene, therefore, could be assigned to the band 8q23-
      >8q24.1.

PMID- 8258103
TI  - [Effect of Rheum officinal on the proliferation of renal tubular cells in vitro].
AB  - Rat renal tubules were isolated and grown in culture medium. The effects of rheum
      officinal (RO) on the proliferation of renal tubular cells were investigated. In
      culture, the addition of the sera obtained from the rat fed with RO inhibited
      significantly the proliferation of renal tubular cells, and the effect become
      even more strong with the increase of the dosage or the long time of
      administration of RO to the rat. The ingredient RO--emodin added directly to
      culture medium suppressed the proliferation of renal tubular cells in a dose
      dependent manner, as measured by the uptake of radiolabeled thymidine. This
      observation may help explain the beneficial effects of RO in the treatment of
      chronic renal failure.

PMID- 8258104
TI  - [Experimental study of portal hemodynamic changes after hepatic artery
      embolization].
AB  - We studied portal hemodynamic changes by using duplex Doppler in 10 pigs with
      hepatic artery embolization (HAE) and hepatic artery ligation (HAL) and in 5 with
      HAL only. Serum concentration of alkaline phosphatase, ALT, direct and indirect
      bilirubin were determined simultaneously. Hepatic angiography and hepatic
      vascular cast were performed in the 5 pigs, and pathological examination in
      others. Portal venous velocity (PVV) and portal blood flow (PBF) increased after
      HAE, ALP, ALT, direct indirect bilirubin slightly elevated (P > 0.05) in the two
      groups after operation and most of them decreased subsequently within 7 days.
      Linear regression of PBF with ALP, ALT, direct and indirect bilirubin occurred in
      the experimental group. Liver necrosis was seen in all pigs of the experimental
      group and only one in the control group. Angiography and vascular cast showed
      that hepatic artery collaterals occurred at the portal hilus in the two groups
      and were more rich in the control group. Extrahepatic and intrahepatic arterial
      collaterals were seen from 1 to 3 weeks after HAE. The estimation of PVV and PBF
      by duplex Doppler may reflect the development of collaterals indirectly and is
      helpful in assessing the effect of HAE.

PMID- 8258105
TI  - [Experimental observation of high portal venous resistance in dogs].
AB  - To study the relationship between portal resistance and formation of portal
      hypertension, we designed a high portal systemic resistance model by injecting
      bletilla hyacinthina into the intrahepatic portal venulae through the portal vein
      in 9 dogs. The portal pressure was measured and the portal hemodynamics studied
      by ultrasonic Doppler before operation, and the data were collected with re
      laparotomy after 10, 20 days respectively. Liver function, portal collateral
      circulation and liver histology were also observed. Our results suggest that the
      portal high resistance could cause portal hypertension. The elevation of FPP was
      maintained and portal blood flow was increased constantly in different degrees.
      The veins of the abdominal wall and esophagus were dilated slightly. Histological
      study of the liver showed fibrotic hyperplasia in the portal area. Liver function
      was not markedly changed except elevation of ALP. It seems that the combination
      of portal resistance and portal hyperdynamics are the necessary pathogenic factor
      of formation of portal hypertension.

PMID- 8258106
TI  - [Pathogenesis of skin pathologic changes and ulceration].
AB  - Twenty-six patients with venous insufficiency and 15 normal controls were studied
      by local skin pathological and ultrastructure changes. Transcutaneous oxygen
      tension (Tcpo2) and tPA, PAI of venous blood were measured. Biopsies from the
      ulcerating and liposclerosis area showed pericapillary fibrins. The patients with
      severe venous disease resulting in liposclerosis or ulceration of the goiter area
      had Tcpo2 levels lower than the controls and patients with venous insufficiency
      but no skin changes. The more serious the skin changes in patients with venous
      insufficiency, the lower the fibrinolysis activity. We conclude that
      extravascular deposition of fibrins in patients with venous disease which block
      the diffusion and exchanges of oxygen between the blood and tissue is an
      important factor in the development of venous ulcerations. The decrease of
      fibrinolysis activity led to the decrease of removing pericapillary fibrins
      deposition, combined with extravascular fibrin caused venous ulceration.

PMID- 8258107
TI  - [Clinical significance of thyrotropin measurement by immunoradiometric assay and
      thyrotropin-releasing hormone test].
AB  - The levels of serum TSH were measured by a sensitive immunoradiometric assay
      (IRMA) method and the responses of TSH to TRH stimulation were observed in three
      groups of hyperthyroidism, primary hypothyroidism and secondary hypothyroidism.
      The levels of serum TSH were found to be undetected in 98% (1/51) of the patients
      with hyperthyroidism, very high in 100% (35/35) of the patients with primary
      hypothyroidism and normal in 91% (30/33) of the patients with secondary
      hypothyroidism. TRH test showed no responses of TSH in all patients with
      hyperthyroidism, high responses in all patients with primary hypothyroidism and
      blunt responses in 69% (11/16) of patients with secondary hypothyroidism. The
      results indicate that the measurement of serum TSH by IRMA is a sensitive index
      in the diagnosis of hyperthyroidism and primary hypothyroidism, but can not be
      differentiated the secondary hypothyroidism from normal conditions. TRH test may
      be helpful in the differential diagnosis between secondary hypothyroidism and
      normal conditions.

PMID- 8258108
TI  - [Changes in 6 trace elements during development of normal fetus vertebrae].
AB  - Six elements: calcium, iron, zinc, copper, manganese and magnesium were detected
      in the central epiphyses of first lumber vertebrae in 60 normal aborted fetus,
      aging from 9 to 32 weeks, by method of AAS. Iron, copper, manganese and zinc
      reached to their high levels during 9-20 weeks, which were related to the
      formation of cartilage vertebrae. Calcium and magnesium, showed a significant
      relationship, and then gradually got to their high value after 16 weeks after
      ossification and remained at a constant level during later period. The data
      indicated that different elements should be given in different stage of fetus
      development.

PMID- 8258109
TI  - [Advances in the research on molecular biology of parathyroid hormones].

PMID- 8258110
TI  - [Current status of the diagnosis of esophageal chest pain].

PMID- 8258111
TI  - Position paper on allergen immunotherapy. Report of a BSACI working party.
      January-October 1992.

PMID- 8258112
TI  - Relationship between periventricular lucencies on computed tomographic scans and
      vascular dementia.
AB  - We evaluated 48 consecutive patients with periventricular lucencies (PVL) on CT
      scan of brain to determine the clinical significance of this finding. Twenty-one
      (43.7%) patients were demented; 27 (56.3%) patients had no dementia but had
      various other diseases. PVL were frequently associated with hypertension and
      previous stroke. We used a PVL scoring system to evaluate the degree of PVL. When
      the score was greater than 3.5, the sensitivity and specificity in separating
      vascular dementia from other diseases with PVL were 78% and 67% respectively
      (Kappa = 0.42). We conclude that although mild PVL may be a frequent but non
      specific finding in patients with hypertension or previous stroke, moderate and
      severe PVL should raise the possibility of vascular dementia.

PMID- 8258113
TI  - Left atrial appendage smoke-like echo in dilated cardiomyopathy: its clinical
      significance and relation to left atrial appendage function.
AB  - To elucidate the clinical significance and pathogenesis of left atrial appendage
      smoke-like echo in dilated cardiomyopathy (DCM), clinical history and
      transesophageal echocardiographic assessment of left atrial appendage (LAA)
      anatomy and function were studied in 18 DCM patients with smoke-like echo (SE),
      34 patients with DCM but no smoke-like echo and in 14 age-matched normal
      subjects. Patients with SE had a larger left atrial appendage area, a lower peak
      LAA systolic flow velocity (PLAAV), a greater incidence of atrial fibrillation,
      with both left atrial appendage thrombi and a history of arterial embolic
      episodes, than did patients without SE. Patients in sinus rhythm with SE had a
      minimal LAA area (5.0 +/- 3.0 cm2) larger than that in the no SE group (3.0 +/-
      1.6 cm2) (p < 0.05), and LAA ejection fraction (18 +/- 10%) and PLAAV (24 +/- 9
      cm/sec) less than that in the no SE group (40 +/- 11% and 39 +/- 16 cm/sec,
      respectively) (P < 0.05). Patients with atrial fibrillation (AF) and SE had PLAAV
      (15 +/- 6 cm/sec) less than that in AF patients without SE (30 +/- 12 cm/sec) (p
      < 0.05). It is concluded that smoke-like echo in LAA is an indicator of DCM
      patients with an increased thromboembolic risk usually associated with dilated
      and poorly contractile LAA.

PMID- 8258114
TI  - Treating carcinomatous pleural effusion by intrapleural injection of OK-432 in
      patients with non-small-cell lung cancer.
AB  - The effect of intrapleural injection of OK-432, a streptococcal preparation, for
      management of carcinomatous pleural effusion was investigated in patients with
      non-small cell lung cancer (NSCLC). Ten patients, including 5 men and 5 women
      with performance status 2-3(ECOG) and average age of 66.4 years, received OK-432
      for different times after the tumor burden in effusion was relieved with adequate
      drainage. The response rate was 100% in terms of decreased reaccumulation of
      pleural fluid, improvement of general status, and disappearance of tumor cells in
      the fluid. The adverse effects of this treatment were mild-including fever,
      chills, chest pain and nausea-and all were tolerable to patients. Median survival
      time was 4.5 months after treatment. This preliminary report indicates that
      intrapleural injection of OK-432 is an effective alternate method for management
      of carcinomatous pleural effusion to improve the quality of life for terminally
      ill cancer patients.

PMID- 8258115
TI  - Postoperative pain relief: lumbar and thoracic epidural morphine in thoracotomy.
AB  - Twenty-two patients undergoing thoracotomy were enrolled in a controlled,
      randomized trial to compare the effects of thoracic (group T) or lumbar (group L)
      epidural morphine in relieving postoperative pain. Epidural morphine was given as
      the patient first complained of pain in the recovery room. The effect of epidural
      morphine on pain relief was assessed by visual analogue scale and subjective
      grade. All patients were investigated 0, 10, 20, 30, 40, 50, 60, 75, 90, 105 and
      120 minutes after a single bolus injection of epidural morphine. In assessment of
      pain relief by visual analogue scale, the difference between two groups was
      statistically significant (p < 0.05), evaluated 20, 30 and 40 minutes following
      treatment. There was no significant difference between two groups with regard to
      the effect of morphine as assessed by subjective grading. We concluded that
      thoracic epidural morphine took effect faster than lumbar epidural morphine.
      However, the effects of both kept similar since 50 minutes after morphine
      injection.

PMID- 8258116
TI  - Program description and preliminary health survey data in Kin-Hu, Kinmen.
AB  - The study subjects were those over 30 years of age in Kin-Hu, Kinmen. From
      January to February 1991, demographic data, physical data, life style and blood
      chemistry parameters were collected from 2929 respondents (1368 men and 1561
      women) out of 4475 eligible subjects. The study, conducted by the Yang-Ming
      Crusade, used a structured questionnaire and venipuncture technique. After
      clarifying missing values, a total number of 2868 (64.1%; 1334 men and 1534
      women) subjects had completed the data set. Of the total subjects, 32.3% were 30
      39 years of age, 24.3% were 40-49 yrs, 22.4% were 50-59 yrs, and 21.0% were above
      60 years old. Fifty-two percent of men and 2.8% of women, were current smokers.
      Most of the surveyed subjects described themselves as having infrequent physical
      activity (men vs. women, 66.4% vs. 81.0%, p < 0.001). Men had significantly lower
      body mass index (BMI) and higher waist-hip ratio (W/H) than women (BMI: 22.9 +/-
      3.2 vs. 23.2 +/- 3.7, p < 0.01; W/H: 0.89 +/- 0.06 vs. 0.84 +/- 0.07, p < 0.01).
      Men also had higher fasting plasma glucose (FPG), systolic/diastolic blood
      pressure (SBP/DBP) than women (FPG: 99 +/- 25.3 vs. 95.7 +/- 25.3 mg/dl, p <
      0.0001; SBP: 132.1 +/- 19 vs. 126.4 +/- 21.5 mmHg, p < 0.0001; DBP: 80.4 +/- 12.5
      vs. 76.5 +/- 12.3 mmHg, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258117
TI  - [Urethral stent: a preliminary report].
AB  - Despite recent progress in endoscopic and reconstructive urology, the management
      of urethral strictures remains a challenge to all urologists. Repeated urethral
      dilation and endoscopic optic urethrotomy may cure the short urethral strictures,
      but they are frustrating and time-consuming both for the patient and the
      physician. Intermittent self-catheterization, which is suggested to maintain a
      satisfactory urethral lumen, is not well accepted by many patients. Urethroplasty
      procedure usually is successful in the treatment of traumatic strictures but it
      requires surgical skills and expertise to which few patients have easy access. We
      describe a new treatment for urethral strictures with the use of the urethral
      Wallstent, which is self-expanding and made of stainless steel, in 4 males with
      difficult urethral stricture (3 recurrent strictures and 1 fresh case). The
      results are satisfactory with less complications. It is a simple, safe and
      effective alternative to other surgical interventions in patients with
      intractable urethral stricture.

PMID- 8258118
TI  - [The clinical effect of slow releasing nicotinate on hyperlipemic impotent
      patients].
AB  - Perycit (Pentaerythriol Tetranicotinate), a slow releasing drug, is one of the
      drugs used for treating hyperlipemia. Patients with erectile dysfunction
      (impotence) associated with hyperlipemia increasingly seek help at urological
      services. This study investigates the clinical effect, both objective and
      subjective of Perycit on anti-hyperlipemia as well as on impotence. Twenty
      patients with a more than one year history of impotence with hyperlipemia were
      enrolled in this randomized, single-blind study. Decrease of total cholesterol,
      and triglyceride, as well as the increase of high density lipoprotein cholesterol
      in the study group (Perycit, 500 mg, tid, for 3 months) were significantly
      different from the pre-treatment period and in the control group (Trental, 100
      mg, tid, for 3 months) (p < 0.05 or p < 0.01). Moreover, improvement in sexual
      function was shown to be better in the study group than in either the
      pretreatment period and control groups, objectively and subjectively (p < 0.05 or
      p < 0.01). Tolerable facial flush was found in 3 of these 20 patients, but no
      major side effects were encountered. In conclusion, this study indicates Perycit
      is effective for anti-hyperlipemia as well as for aiding improvement of sexual
      dysfunction. Since it is a slow-releasing preparation, the side effect is
      minimal. It is recommended for patients with hyperlipemia alone, or those who
      suffer from combined erectile dysfunction.

PMID- 8258119
TI  - [Seasonal variation of peptic ulcer hemorrhage].
AB  - Retrospectively analysis of 2015 episodes of duodenal ulcer (DU) hemorrhage, and
      874 episodes of gastric ulcer (GU) hemorrhage over a 5-year period (April, 1987
      March, 1992) evaluated seasonal incidence. For duodenal ulcers, the highest
      incidence occurred in January, or a total of 231 episodes over 5 years (4.6% of
      all medical admission), whereas the lowest incidence was in August, with only 101
      episodes in the same period (2.1% of medical admission). There was a
      statistically greater incidence of DU bleeding during the relatively cool winter
      months, December to March (835 episodes, 4.3%) vs. the warmer summer months, June
      to September (500 episodes, 2.5%; p < 0.05). For gastric ulcers, the incidence of
      bleeding was highest in January and February (1.9%) and lowest in September
      (1.1%). As with DU, GU bleeding was more common in winter (332 episodes, 1.7%)
      than in summer (243 episodes, 1.2%; p < 0.05). Over one year of this series (DU
      bleeds: 390, GU bleeds: 167), there was no predilection for a particular day of
      the week. Of patients evaluated in that year, 87 with DU and 17 with GU had
      history of bleeding at least one time before. However, there was no seasonal
      correlation with the previous bleeding episodes. It was concluded that there is
      seasonal variation in the incidence of peptic ulcer hemorrhage in our country.
      However, it is not possible to predict when in the year patients are likely to
      rebleed.

PMID- 8258120
TI  - Hemolytic disease of the newborn caused by maternal anti-Dib: a case report in
      Taiwan.
AB  - Possibly the first case of hemolytic disease caused by anti-Dib in a Chinese
      infant is reported. The infant developed jaundice soon after birth; based on
      study, the jaundice has been diagnosed as a result of maternal anti-Dib which was
      most likely induced by previous pregnancies. The phenotype of the mother's red
      cells was Di (a+b-). The frequency of the Dia antigen among Chinese in Taiwan is
      3.2%. In Orientals, hemolytic disease of the newborn caused by maternal anti-Dib
      is likely to be more severe than that caused by anti-Dia.

PMID- 8258121
TI  - Systemic lupus erythematosus with pure red cell aplasia: a case report.
AB  - Pure red cell aplasia (PRCA) is an unusual early manifestation of systemic lupus
      erythematosus (SLE). Review of the 13 cases in literature revealed that the
      immune system played a significant role in disease pathogenesis.
      Immunosuppression has been thought to be the cause of the efficacy of
      corticosteroids in treatment. The case of a 28-year-old woman with SLE is
      described. She presented with PRCA, but has had good response to corticosteroid
      therapy.

PMID- 8258122
TI  - Acute iron intoxication: a case report with ferric chloride ingestion.
AB  - A 24 y/o male, after attempting suicide by ingesting liquid ferric chloride,
      presented with protracted vomiting and epigastric pain. He was noted to have
      leukocytosis, a metabolic acidosis and an elevated serum iron level. Hemorrhagic
      gastritis, coagulation defects and an increase in urine beta 2-microglobulin,
      indicating renal tubular damages were found in the following day. He later
      recovered after treatment with deferoxamine and good supportive care. This is
      Taiwan's first reported case of acute iron intoxication in an attempted suicide.
      We discussed the characteristics of this liquid form of iron intoxication, the
      limitations of local laboratories in providing support and how to diagnose and
      treat acute iron intoxication without waiting for serum iron and total iron
      binding capacity levels. In conclusion, to evaluate the severity of iron
      intoxication, a deferoxamine challenge test and the severity of symptoms and
      signs should be assessed without relying only on serum iron and total iron
      binding capacity levels. Deferoxamine and good supportive care should be given to
      all serious iron intoxications.

PMID- 8258123
TI  - Ataxic hemiparesis following thalamic hemorrhage: a case report.
AB  - A 66-year-old man suddenly developed right ataxic hemiparesis. Sensations,
      somatosensory-evoked potentials and visual-evoked potentials were normal.
      Magnetic resonance imaging and computed tomography of the head showed an acute
      hemorrhage mainly in the ventrolateral nucleus of the left thalamus. Interruption
      of the dentatorubrothalamocortical pathway at the level of the damaged
      ventrolateral nucleus of the thalamus, and the initial edema compressing the
      corticopontine tract in the posterior limb of the internal capsule might have
      contributed to the ataxia. Hemiparesis was related primarily to transient edema
      compressing the corticospinal tract in the posterior limb of the internal
      capsule.

PMID- 8258124
TI  - Glomus tumor of the stomach: a case report.
AB  - The histologic and ultrastructural features of a gastric glomus tumor are
      presented with a brief review of the literature. Initially interpreted as
      carcinoid, the tumor occurred in a 41-year-old female who was first diagnosed by
      radiological examination and microscopic histological study of an endoscopic
      biopsy specimen. Glomus tumor was confirmed by further study of multiple sections
      of a surgical specimen and by electron microscopy. Correct identification of this
      essentially benign, very rare gastric tumor can prevent unnecessary radical
      operative procedures.

PMID- 8258125
TI  - [Malignant transformation of multiple gastric adenomatous polyps in a teenage
      girl: a case report].
AB  - A 14-year-old female was found to have gastric polyposis by gastroscopy and
      barium meal study. During operation, multiple polyps in different sizes were
      noted over the whole stomach, the largest one measured 6 x 6 x 4 cm. The
      pathological report was adenomatous polyps. After 4 years, the polyps finally
      transformed to multifocal gastric adenocarcinoma. The relationship between
      gastric polyps and gastric adenocarcinoma, and the management of gastric
      polyposis were discussed.

PMID- 8258126
TI  - Is the increasing frequency of laparoscopic bile duct injury justifiable?

PMID- 8258127
TI  - Anterior mediastinal masses after cancer therapy: recurrences or benign lesions?

PMID- 8258128
TI  - Beware of the Trendelenburg position during prolonged laparoscopic procedures.

PMID- 8258129
TI  - Bile duct injury during laparoscopic cholecystectomy.
AB  - OBJECTIVE: To determine the nature of bile duct injuries during laparoscopic
      cholecystectomy, the treatment of these injuries and patient outcome. DESIGN:
      Case series review. SETTING: Two tertiary care hospitals. PATIENTS: Twenty-one
      patients (average age 37 years) who sustained bile duct injuries during
      laparoscopic cholecystectomy over a 2-year period. Two groups were analysed:
      patients whose injury was recognized intraoperatively (9 patients) and patients
      in whom it was diagnosed postoperatively (12 patients). INTERVENTIONS:
      Laparoscopic cholecystectomy, duct-to-duct repair over a T tube, Roux-en-Y
      hepaticojejunostomy, endoscopic cholangiopancreatography (ERCP), percutaneous
      transhepatic cholangiography (PTC). RESULTS: Misidentification of the common duct
      during laparoscopic cholecystectomy, resulting in accidental division or
      resection of a portion of the duct, and obstruction of the duct by hemoclips were
      the most common types of injury. Pain, jaundice and bile collections were the
      typical presenting features of injuries that became evident after laparoscopic
      cholecystectomy. ERCP and PTC accurately defined the injuries. Immediate duct-to
      duct repair over a T tube was associated with a high failure rate. Twenty of the
      21 patients required Roux-en-Y hepaticojejunostomy for definitive treatment.
      There were no deaths. CONCLUSIONS: Proper identification of the pertinent anatomy
      will prevent the majority of these injuries. Prompt radiographic visualization of
      the biliary tract is indicated in patients who have pain, jaundice and bile
      collections postoperatively. A hepaticojejunostomy is the procedure of choice for
      repair of these bile duct injuries.

PMID- 8258130
TI  - Use of the external fixation apparatus for percutaneous insertion of pins in the
      distal one-third of the radius: an anatomic study.
AB  - OBJECTIVE: To assess the risk of soft-tissue injury during percutaneous placement
      of external fixation pins in the proximal radius. DESIGN: An anatomic study with
      embalmed cadaver limbs. SETTING: Hand and upper limb centre at a university
      affiliated hospital. INTERVENTIONS: Two 4-mm Hoffman half pins were
      percutaneously placed along the dorsoradial ridge of the radius, four finger
      breadths proximal to the radial styloid process. MAIN OUTCOME MEASURES: Injuries
      to soft tissues including tendons, nerves and vessels were noted. RESULTS: Nerve
      or tendon injuries occurred in 7 of 26 forearms. Three pins transfixed either the
      superficial branch of the radial nerve or lateral antebrachial cutaneous nerves.
      Tendon injuries included the brachioradialis in two forearms, the extensor carpi
      radialis brevis in three forearms, and the extensor carpi radialis longus and the
      abductor pollicis longus in one forearm each. CONCLUSIONS: Percutaneous pin
      placement in the distal radius is unsafe. The authors recommend open pin
      placement for fractures of the distal radius.

PMID- 8258131
TI  - Acute abdominal emergencies in patients on long-term ambulatory peritoneal
      dialysis.
AB  - OBJECTIVE: To review intercurrent abdominal emergencies in patients receiving
      long-term peritoneal dialysis on an ambulatory basis. DESIGN: A chart review.
      SETTING: Tertiary care referral centre. PATIENTS: Seven patients receiving long
      term peritoneal dialysis, who suffered an acute abdominal emergency during a 7
      year study period. INTERVENTIONS: Laparotomy with appropriate management
      depending on the findings. Antibiotic therapy and dialysate culture. RESULTS: In
      all patients the acute abdominal process involved the colon: five patients had
      perforated diverticulitis and two had ischemic colitis. The death rate overall
      was 57%. Peritonitis in these patients was difficult to differentiate from the
      peritonitis that occurs commonly in patients on long-term peritoneal dialysis. As
      a result there was a delay in the initiation of therapy ranging from 2 to 27
      days. CONCLUSIONS: Coincidental abdominal emergency should be considered when
      patients receiving long-term peritoneal dialysis on an ambulatory basis present
      with peritonitis that does not respond to established antibiotic protocols and
      when culture results show evidence of multiple enteric organisms.

PMID- 8258132
TI  - Pediatric free tissue transfer: an evaluation of 99 cases.
AB  - OBJECTIVE: To evaluate the results of free tissue transfers in children who
      undergo reconstructive surgery. DESIGN: Case series chart review. Mean follow-up
      longer than 2 years. SETTING: Two tertiary care pediatric hospitals. PATIENTS:
      Consecutive sample of 99 children. INTERVENTIONS: Free tissue transfers for
      reconstruction of a variety of defects. MAIN OUTCOME MEASURES: Indications,
      operations, complications, survival. RESULTS: The most common indications were
      for restoration of muscle function and for difficulties with soft-tissue
      coverage. Multiple donor sites were used, with the gracilis muscle, fibula,
      latissimus dorsi and groin flaps predominating. The overall survival rate was
      99.0%. Complications were common, with an overall rate of 59.6%; most were graded
      as minor or moderate. CONCLUSIONS: Meticulous planning is paramount in achieving
      a successful outcome. Complications are common but do not include vascular spasm.
      Free tissue transfers can be successfully completed in small children despite the
      dimensions of the tissues.

PMID- 8258133
TI  - Blunt traumatic liver injury associated with clostridial infection of early
      onset.
AB  - Hepatic clostridial infections associated with blunt abdominal trauma are rare.
      Generally they occur from 2 weeks to 3 months after injury and are thought to
      result from the growth of normal enteric organisms, which are carried to the
      liver by the portal venous system and infect devitalized tissue. The authors
      describe two patients in whom the hepatic infection became established in less
      than 24 hours after injury and was due to Clostridium spp. The patients were
      successfully treated by hepatic resection and combination antimicrobial therapy.
      Hyperbaric oxygen was used as an adjunct in one case.

PMID- 8258134
TI  - Unusual isolated common bile duct injury after blunt trauma.
AB  - Isolated injury to the extrahepatic biliary tree after blunt trauma is rare. The
      authors describe the case of a 17-year-old boy who suffered such an injury after
      falling over the handlebar of his motorcycle. Ultrasonography, computed
      tomography and abdominal paracentesis were used to make the diagnosis. At
      laparotomy there was a partial tear of the common bile duct at its junction with
      the cystic duct. A cholecystectomy was performed and a T tube inserted. The
      patient recovered without complication. The authors emphasize that only awareness
      of the condition and diagnostic confirmation by computed tomography and abdominal
      paracentesis can expedite the diagnosis and treatment. The choice of surgical
      repair must be individualized according to the clinical findings and the nature
      of the injury.

PMID- 8258135
TI  - The cardiac surgery program at the Royal Columbian Hospital: review of the first
      fiscal year.
AB  - From a budgetary viewpoint, the authors summarize the operative experience of the
      cardiac surgery program at the Royal Columbian Hospital during its first fiscal
      year of operation. The program was funded for 250 cardiopulmonary bypass (CPB)
      procedures: $16,800 per CPB procedure ($4.2 million for the program). The 250 CPB
      procedures were performed on 248 patients. The 30-day operative mortality was 2%.
      Thirty patients (12.1%) underwent a second operation for complications or delayed
      primary closure of the sternum, or both; the complications included aortic
      prosthetic perivalvular leaks in 2 patients. Eight patients (3.2%) required
      insertion of an intra-aortic balloon pump preoperatively to stabilize their
      condition; 10 others (4.0%) required intra-aortic balloon pump insertion at
      surgery to correct low-cardiac-output syndrome. Blood products were needed for
      149 (59.6%) of the 250 CPB procedures. The average hospital stay was 10.4 days
      for noncoronary procedures and 9.0 days for coronary procedures.

PMID- 8258136
TI  - Thoracoscopic intracavitary drainage for pneumothorax secondary to bullous
      emphysema.
AB  - Most patients with spontaneous pneumothorax secondary to bullous emphysema are
      successfully managed by chest-tube drainage. Occasionally a very large air leak
      prevents full lung expansion. The authors report on a patient in whom
      thoracoscopic intracavitary drainage of a leaking bulla led to rapid resolution
      of the pneumothorax and obliteration of the bulla. A large bronchopleural fistula
      was converted to a controlled bronchocutaneous fistula. The authors conclude that
      when conventional management fails to provide full lung expansion in cases of
      pneumothorax secondary to bullous emphysema, thoracoscopic intracavitary drainage
      is useful.

PMID- 8258137
TI  - Pica in the mentally handicapped: a 15-year surgical perspective.
AB  - OBJECTIVE: To review the general surgical management of mentally handicapped
      persons with pica. DESIGN: A study of hospital records and a review of the
      current literature. SETTING: A community hospital. PATIENTS: Thirty-five patients
      from a large institution for the mentally handicapped were treated for well
      documented pica on 56 occasions at the Orillia Soldiers Memorial Hospital between
      1976 and 1991. INTERVENTIONS: Endoscopy and laparotomy for the removal of foreign
      bodies or to close perforations. RESULTS: Fourteen (25%) cases of pica were
      managed by observation only, but 42 (75%) cases required surgical intervention.
      There were 34 laparotomies. The complication rate was 30% and the death rate 11%.
      CONCLUSIONS: Pica is a serious health risk for mentally handicapped patients.
      Diagnosis and postoperative care can be difficult. Pica should be suspected in
      mentally handicapped patients with gastrointestinal symptoms.

PMID- 8258138
TI  - Noncemented stem tibial component in total knee replacement: the 2- to 6-year
      results.
AB  - OBJECTIVE: To determine if the addition of a stem to the tibial component in
      noncemented total knee replacement affects sinkage of that component or
      micromotion. DESIGN: A cohort of 176 consecutive cases with no exclusions. Follow
      up ranged from 2 to 6 years. SETTING: A university-affiliated institution
      specializing in elective orthopedic surgery. PARTICIPANTS: All 176 patients had
      arthritis of the knee, mainly osteoarthritis. All agreed preoperatively to
      prolonged postoperative follow-up. INTERVENTION: Noncemented total knee
      replacement with the Tricon M long-stem tibial component. MAIN OUTCOME MEASURES:
      Hospital for Special Surgery rating system for clinical results and degree of
      tibial sinkage and stem lucency seen radiologically. RESULTS: Eight (4.5%) of the
      176 prostheses required revision, none for sinkage. Of the remaining 168 knees,
      156 (92.9%) scored good or excellent, 6% fair and 1.2% poor. Sinkage occurred in
      3%, but was not of sufficient severity to require revision. No lucency was
      visible in 33.8% of stems, partial lucency in 62%, complete lucency with the
      lines being parallel to the stem in 3.5% and complete lucency with divergent
      lines, indicating a loose implant, in 1.7%. Lucency, when present, was seen
      mainly in the lateral view, seldom in the anteroposterior view. There was no
      correlation between radiologic results and clinical results. CONCLUSIONS: The
      addition of a metaphyseal stem reduces the incidence of sinkage of the tibial
      component in total knee replacement. The stem largely solves the problem of
      mediolateral micromotion but does not completely prevent anteroposterior
      micromotion.

PMID- 8258139
TI  - Noncemented, porous ingrowth knee prosthesis: the 3- to 8-year results.
AB  - OBJECTIVE: To determine the principal long-term problems encountered in
      noncemented total knee replacement. DESIGN: A cohort of 252 consecutive cases of
      total knee replacement with no exclusions. Follow-up ranged from 3 to 8 years.
      SETTING: A university-affiliated institution specializing in orthopedic surgery.
      PARTICIPANTS: All 252 patients had arthritis of the knee, mainly osteoarthritis.
      All agreed preoperatively to prolonged postoperative follow-up. INTERVENTION:
      Noncemented total knee replacement with the Tricon M prosthesis, which has a
      metal-backed patella. MAIN OUTCOME MEASURES: The Hospital for Special Surgery
      rating system for clinical results and the radiologic results, including reasons
      for revision surgery. RESULTS: Thirty-five prostheses were revised: 11 prostheses
      because of patellar wear only; in 13 prostheses the tibial component (mainly a 6
      mm unit) and patella were revised because of wear; 6 prostheses were revised for
      sepsis, 4 for reflex sympathetic dystrophy and 1 only for sinkage of the tibial
      component. Of the remaining 217 prostheses, 88% scored good or excellent, 6% fair
      and 6% poor. CONCLUSIONS: The single most common cause of failure was
      polyethylene wear. This was associated with the metal backing of the patella and
      the use of thin, polyethylene tibial components.

PMID- 8258140
TI  - T-cell receptor gamma delta diversity and specificity of intestinal
      intraepithelial lymphocytes: analysis of IEL-derived hybridomas.
AB  - The phenotype, T-cell antigen receptor (TCR) usage and specificity of intestinal
      intraepithelial lymphocytes (IEL), and hybridomas derived from IEL have been
      examined. In young conventionally reared mice, approximately 50% of the IEL
      express TCR alpha beta and 50% express TCR gamma delta, although there is
      considerable variation between individuals. Here we demonstrate that T-cell
      hybridomas can be prepared from freshly isolated BALB/c mouse IEL. The expressed
      TCR of these hybridomas reflects the TCR isotype distribution of the IEL
      population. Analysis of the gamma delta TCR expressed by the hybridomas
      demonstrates that IEL express a greater number of TCR V gene segments than has
      been reported for gamma delta T cells in several other epithelial sites. At least
      five types of gamma delta TCRs are expressed by a panel of BALB/c IEL hybridomas,
      although use of the gamma delta TCR V gene repertoire clearly is not random. Some
      TCR gamma delta cells and gamma delta hybridomas have been reported to recognize
      purified protein derivative (PPD); however, none of the IEL hybridomas secreted
      IL-2 in response to PPD. These data suggest that most TCR gamma delta IEL are not
      likely to be PPD reactive.

PMID- 8258141
TI  - T cell-dependent differentiation of human B cells into IgM, IgG, IgA, or IgE
      plasma cells: high rate of antibody production by IgE plasma cells, but limited
      clonal expansion of IgE precursors.
AB  - The development of human functional Ig precursors into plasma cells expressing
      IgM, IgG, IgA, or IgE was compared. Purified human B cells were stimulated at
      limiting dilution with irradiated EL4 helper cells, IL-2, and IL-4. B cells
      proliferated exponentially until Day 8 of culture. Nondividing plasma cells of
      all isotypes were detectable in ELISPOT assays between Days 8 and 10 and secreted
      1.8 +/- 0.7 ng antibody per cell within 24 hr. This indicates that plasma cells
      of all isotypes, including IgE, bear a comparable potential to secrete antibody.
      It further shows that Ig switching does not delay the development into IgE plasma
      cells, despite that switching from IgM to IgE in vitro required 6 days of IL-4
      action. The proliferation and Ig production by B cells readily declined after
      Days 8 and 10, respectively, and could not be prolonged by restimulating B cells
      with fresh helper cells and lymphokines in secondary cultures. This indicates
      that B cells have developed into nondividing, high rate Ig-secreting plasma cells
      within 9 days, and that they do not differentiate any further under the applied
      conditions. In contrast to IgM, IgG, and IgA committed B cells, IgE switched
      cells did not undergo clonal expansion, since the numbers of functional IgE
      precursors corresponded to the maximal numbers of IgE-secreting plasma cells,
      whereas the numbers of IgM-, IgG-, or IgA-secreting cells exceeded the number of
      functional precursors 15-fold. The results demonstrate that human B cells of all
      isotypes, including IgE, have the potential to secrete antibody at a comparably
      high rate, and that the IL-4-induced switch process does not delay the
      differentiation into plasma cells.

PMID- 8258142
TI  - An ovalbumin peptide-specific cytotoxic T cell clone with antigen self
      presentation capacity uses two distinct mechanisms to kill target cells.
AB  - Cloned 10BK.1 T cells with specificity for the ovalbumin peptide OVA257-264 are
      representative of a novel cell type within the CD8+ subset of T cells. In the
      presence and in the absence of added antigen presenting cells these T cells react
      toward antigen (Ag) by proliferation and lymphokine production. These data
      suggest self-presentation of the Ag by 10BK.1 cells. Here we present evidence
      that 10BK.1 cells exhibit cytotoxic activity that involves two different
      cytotoxic effector mechanisms. (i) One mechanism is fast killing activity,
      apparent within 4 hr. Constitutive mouse T cell-specific proteinase-1 (MTSP-1)
      activity, constitutive expression of MTSP-1 RNA, increased by Ag challenge, and
      Ag-inducible perforin RNA expression were observed. Electron microscopic dense
      granules of the CTL were oriented toward Ag-pulsed target cells. The fast form of
      cytotoxicity was triggered by Ag recognition and by contact with IL-2. (ii) The
      other mechanism is slow cytolytic activity, manifested within 2 days. This
      activity was contained in the supernatant of 10BK.1 cells after Ag activation. It
      was inhibited by monoclonal anti-TNF antibodies and therefore presumably
      represents TNF alpha/beta. Cytotoxic T cells capable of antigen self-presentation
      may be responsible for tissue damage during bacterial and viral infections.

PMID- 8258143
TI  - Preservation of the specificity of superantigen to T cell receptor V beta
      elements in the absence of MHC class II molecules.
AB  - Superantigens interact with specific V beta elements of the T cell receptor and
      consequently activate all T cells bearing those elements. The ability of
      superantigens to stimulate T cells depends on the presence of APC that express
      MHC class II molecules on their surface. The question we are addressing is: do
      superantigens have to be seen in context of MHC class II molecules, or can they
      be recognized directly by T cell-receptor elements? We have previously shown that
      the APC requirement for the stimulation of T cells by the streptococcal
      superantigen, pep M5, can be bypassed by the addition of PMA and cytokines or by
      crosslinking CD28 molecules. Here we asked if the response of APC-depleted T
      cells to this superantigen is V beta-restricted and whether in the presence of
      PMA and cytokines the specificity of pep M5 to V beta elements is altered. We
      provide evidence that in the absence of APC, but in the presence of PMA and
      cytokines, the specificity of pep M5 to V beta elements is identical to that
      observed when APC are present, with V beta 2, V beta 4, and V beta 8 being
      significantly expanded. In addition, we ruled out the possibility that the
      response is due to a minor contamination with APC or to the expression of DR
      molecules on T cells because anti-HLA class II monoclonal antibodies did not
      block the reconstituted response, whereas they totally abrogated the response in
      the presence of APC. We conclude that pep M5 does not have to complex with MHC
      class II molecules in order to interact with specific V beta elements. In
      addition, we propose that the inhibitory effects of the anti-class II antibodies
      when APC are present may be due to preventing pep M5 from binding and activating
      APC, thereby blocking the production of costimulatory molecules necessary for T
      cell activation by this superantigen.

PMID- 8258144
TI  - IL2-R alpha chain inhibitory factor (p29) produced by HIV-infected macrophages:
      cell target and mode of action.
AB  - We recently reported that HIV-infected adherent cells spontaneously produce a 29
      kDa protein (p29), most probably of nonviral origin, which inhibits expression of
      the IL2R alpha chain on activated normal T cells. Studying the mode of action of
      this molecule, we observed that monocyte depletion of normal PBMC either by
      plastic adherence or by complement-mediated cytotoxicity using macrophage
      specific monoclonal antibodies abrogated the inhibitory effect of p29. The
      biological activity of p29 in adherent cell-depleted PBMC could be restored
      either with rIL1 or with as little as 10(5) autologous adherent cells/ml.
      Moreover, p29 could not inhibit IL1 biologic activity, nor its binding to IL1
      receptor. In addition, p29 could not inhibit the production of IL1 and TNF alpha
      by normal adherent cells. Positive and negative cell sorting of normal T cells as
      well as two-color immunofluorescence studies revealed that CD8+ subsets are the
      main cell targets of p29, which also mediated an impaired generation of
      alloantigen-specific CTL. Conversely, only a slight inhibitory activity could be
      detected in highly purified CD4+ cells. Our findings suggest that HIV-induced
      production of p29 inhibitory factor by adherent cells may be involved in
      mechanisms responsible for some of the impaired cytotoxic functions observed in
      AIDS patients.

PMID- 8258145
TI  - A novel antigen (H47 Ag) on human lymphocytes involved in T cell activation.
AB  - Surface molecules involved in human T cell activation were investigated using a
      newly developed monoclonal antibody (H47 mAb). H47 antigen (Ag) recognized by H47
      mAb was expressed on approximately 10% of resting T cells (mostly CD4-CD8+), 30%
      of phorbol 12-myristate 13-acetate (PMA)-activated T cells (both CD4+CD8- and CD4
      CD8+), and most NK, B cells, and monocytes in the peripheral blood mononuclear
      cells (PBMC). H47 mAb respectively immunoprecipitated a 100 or 120-kD molecular
      weight (MW) membrane protein of T cells and monocytes under nonreducing or
      reducing conditions, suggesting that H47 Ag consists of a single polypeptide that
      has intramolecular disulfide bonds. H47 mAb significantly enhanced PMA-induced
      proliferation of PBMC in a monocyte-independent fashion. H47 mAb, however, failed
      to enhance T cell proliferation induced by anti-CD3 mAb, anti-CD2 mAb, or
      phytohemagglutinin (PHA). H47 mAb also enhanced PMA-induced interleukin-2
      receptor (IL-2R) expression and IL-2 synthesis, but did not induce a change in
      intracellular free calcium ([Ca2+]i) of T cells. These results suggest that H47
      Ag is a new membrane molecule involved in PMA-induced T cell activation.

PMID- 8258146
TI  - Severe combined immunodeficiency of reduced severity due to homozygosity for an
      adenosine deaminase missense mutation (Arg253Pro).
AB  - Genetic deficiency of adenosine deaminase (ADA) results in varying degrees of
      immunodeficiency, including neonatal onset severe combined immunodeficiency (ADA-
      SCID) and milder, later onset immunodeficiency. We have determined the molecular
      basis of disease in a child from a consanguineous mating with ADA- SCID of
      clinically and biochemically reduced severity, diagnosed at 15 months of age and
      characterized by retention of more immunologic function than is typical of the
      fulminant neonatal onset type. The course was notable for an early predominance
      of bacterial infections and eosinophilia. In contrast to its absence in most ADA-
      SCIDs, residual ADA activity (1-2% of normal) could be detected in EBV
      transformed B cells. Consistent with the increased residual ADA, excretion of the
      substrate deoxyadenosine and accumulation of the toxic metabolite deoxyATP were
      less than seen in ADA- SCID patients with fulminant disease. Sequence analysis of
      cDNA revealed a G853C transversion, predicting a substitution of proline for
      arginine at codon 253 (Arg253Pro). The parents were heterozygous and the child
      was homozygous for the mutation, as shown by sequence analysis of amplified
      genomic DNA. Transient expression of mutant cDNA in Cos cells revealed an
      electrophoretically abnormal, more negatively charged ADA with 1-2% of normal
      activity. These observations are consistent with replacement of positively
      charged arginine by proline, the lower accumulation of toxic metabolites, and the
      milder phenotype. By contrast, transient expression of a Gly216Arg mutant cDNA,
      associated, when homozygous, with neonatal onset ADA-SCID, did not reveal ADA
      activity. Mutations such as Arg253Pro, which retain residual activity of
      monomeric ADA, should be dominant for ameliorating the phenotype in patients
      carrying two different allelic mutations. Identification of additional similar
      mutations may be significant in evaluating the goals for and efficacy of current
      trials of gene and gene product replacement.

PMID- 8258147
TI  - T cell reactivity to acetylcholine receptor in rats orally tolerized against
      experimental autoimmune myasthenia gravis.
AB  - Myasthenia gravis and its animal model experimental autoimmune myasthenia gravis
      (EAMG) represent T cell-dependent autoimmune diseases mediated by antibodies
      against the nicotinic acetylcholine receptor (AChR) of the neuromuscular
      junction. Oral administration of Torpedo AChR to Lewis rats prior to immunization
      with the myasthenogenic Torpedo AChR and complete Freund's adjuvant results in
      the prevention of clinical EAMG, and the suppression of AChR-specific B cell
      responses. To examine the influence of oral tolerance to EAMG on AChR-reactive T
      cells, we determined and enumerated such cells in the popliteal, inguinal, and
      mesenteric lymph nodes, spleen, and thymus by a T cell immunospot assay that is
      based on the secretion of interferon-gamma (IFN-gamma) by antigen-reactive T
      cells. A diminution of such cells was detected in popliteal, inguinal, and
      mesenteric lymph nodes of rats orally tolerized to EAMG compared to unfed or
      vehicle-fed animals. We conclude that oral administration of AChR, in addition to
      preventing clinical signs of EAMG and suppressing AChR-specific B cell responses,
      also counteracts the development of AChR-reactive IFN-gamma-secreting cells in
      certain lymphoid organs.

PMID- 8258148
TI  - Regulation of IgD-receptor expression on murine T cells. I. Characterization and
      metabolic requirements of the process leading to their expression.
AB  - Receptors for IgD (IgD-R) are found on murine CD4+ T cells and T cell clones.
      Previous work has shown that incubation with aggregated (but not monomeric) IgD
      causes the rapid upregulation of IgD-R and enables the T cells to respond with
      augmented helper function in antibody production. In the present study, IgD-R
      upregulation is shown to be (a) rapid, reaching plateau levels by 60 min, (b)
      independent of de novo protein or RNA synthesis, and (c) only slightly reduced at
      4 degrees C. The IgD-R+ T cells present both before and after upregulation of IgD
      R expression are predominantly resting T cells, whose ability to rosette with IgD
      SRBC is inhibited by soluble IgD. The upregulation of IgD-R, even after overnight
      exposure to IgD, does not cause any detectable change in the expression of other
      T cell surface markers. Also characteristic of resting T cells is that they
      exhibit IgD-R in response to IL-2 and IL-4 only after overnight incubation with
      these cytokines, and fail to respond at all to IL-1. In contrast, cloned Th2
      cells, expressing IL-1 and IL-2 receptors, show IgD-R upregulation after a 2-hr
      exposure to IL-1 or IL-2. GM-CSF, TNF-alpha, IL-6, and IL-10 do not modulate IgD
      R expression. T hybridoma cells constitutively express much higher IgD-R levels
      than resting splenic T cells and can be stained with aggregated IgD followed by
      FITC-anti-IgD. Their levels of IgD-R expression decrease, as assayed both by
      rosetting and by staining, on 4-14 hr of incubation with tunicamycin or
      deoxynojirimycin, suggesting that N-linked glycosylation and oligosaccharide
      processing, respectively, are needed for continued expression of IgD-R.
      Tunicamycin-treated cells without detectable IgD-R on their surface still show
      IgD-binding protein in the cell extracts, suggesting that surface expression is
      more dependent on glycosylation of the IgD-R molecules than on the ability to
      bind IgD. Ca2+ ions are needed for optimal binding of IgD to IgD-R, in line with
      previous findings showing IgD-R to be lectin-like in binding carbohydrate rather
      than peptide regions of the IgD molecule.

PMID- 8258150
TI  - Effects of irradiation on development of Theiler's murine encephalomyelitis virus
      (TMEV)-induced demyelinating disease in genetically resistant mice.
AB  - Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV
      IDD), a model for multiple sclerosis, is a chronic T cell-mediated disease.
      Development of clinical symptoms in susceptible mouse strains generally
      correlates with TMEV-specific delayed-type hypersensitivity (DTH) responses.
      These responses, minimal or absent in resistant mouse strains, have been proposed
      as the pathogenic basis for the central nervous system inflammation and
      demyelination characterizing the disease. We demonstrate here that normally
      resistant (C57BL/6 x DBA/2)F1 hybrid mice develop clinical symptoms and DTH
      responses against TMEV after low doses of gamma-irradiation. Parental C57BL/6
      animals remain resistant after similar pretreatment. Thus low-dose irradiation
      elicits a "latent" susceptibility to TMEV-IDD in some, but not all, resistant
      mice. Adoptively transferred spleen cells from syngeneic, unirradiated donors
      reconfer resistance on irradiated, infected B6D2F1 hybrids and reduce DTH
      responsiveness against TMEV, suggesting a protective role for a radiation
      sensitive splenic population(s). The closely related C57BL/6 and C57BL/10 strains
      differ with respect to intrinsic and latent susceptibility.

PMID- 8258149
TI  - Regulation of IgD-receptor expression on murine T cells. II. Upregulation of IgD
      receptors is obtained after activation of various intracellular second-messenger
      systems; tyrosine kinase activity is required for the effect of IgD.
AB  - The presence of IgD receptors (IgD-R) on T cells during a primary response to
      antigen causes augmented antibody production and facilitates priming for a
      secondary response. Cross-linked, but not monomeric IgD leads to a rapid
      upregulation of these receptors on T cells. As shown in the present study, the
      rapid upregulation of IgD-specific receptors is also induced by cross-linking of
      T cell surface molecules known to mediate triggering of T cell activation, such
      as CD3, CD2, and Thy 1. Furthermore, IgD-R are also upregulated by
      pharmacologically active compounds that increase intracellular cAMP and by
      PMA/DiOG plus ionomycin, but not by either PMA or ionomycin alone. The
      upregulation of IgD-R by anti-CD3 is inhibited by both calphostin C and
      herbimycin A, while that due to DiOG plus ionomycin is only inhibited by
      calphostin C. Upregulation of IgD-R by increased cAMP is blocked by HA1004, but
      not by low concentrations of staurosporine or herbimycin A. IgD itself does not
      cause an increase in intracellular cAMP, protein kinase C translocation, influx
      of extracellular Ca2+, or a change in membrane potential. Relatively specific
      inhibitors of these activation pathways, HA1004, calphostin C, and neomycin, also
      fail to interfere with IgD-receptor upregulation by IgD itself. However, tyrosine
      kinase inhibitors, including herbimycin A, tyrphostin C11, and genistein,
      completely prevent the effect of IgD on IgD-R expression. Although an influx of
      Ca2+ is apparently not involved, a role for intracellular Ca2+ in the
      upregulation of IgD-R by IgD on T cells is indicated by the susceptibility to
      inhibition by BAPTA, W7, and FK520. We conclude that activation of at least three
      different second-messenger systems can cause IgD-R upregulation, but that the
      effect of IgD itself requires tyrosine kinase activity, perhaps in an
      intracellular Ca(2+)-dependent manner.

PMID- 8258151
TI  - Analysis of the cellular requirements for the binding of exogenous peptides to
      MHC class II molecules.
AB  - The cellular mechanism regulating the binding of exogenous peptides to MHC class
      II molecule is still an object of controversy. In order to study the cellular
      requirements of peptide binding we have set up an indirect fluorescence assay
      that enables us to detect quantitatively peptide/MHC class II complexes on the
      cell surface of the mouse B lymphoma A20. The absence of binding on several MHC
      class II-negative cell lines and the inhibition of binding in the presence of
      competitor peptides or in the presence of a polyclonal serum against MHC class II
      molecules confirmed the specificity of the assay. A panel of pharmacological and
      physical agents was then used to determine the mechanism of this regulation.
      Binding was not significantly affected by vinblastine or cycloheximide and was
      affected only to a small extent by chloroquine or azide. In contrast to the long
      half-life previously reported for soluble complexes, we found that the half-life
      of a peptide/MHC class II complex expressed on A20 was shorter than 3 hr,
      suggesting that peptide binding might be regulated at the cellular level. The
      energy of activation of peptide binding, estimated from the temperature
      dependence of the rate of peptide binding, was decreased above 27 degrees C,
      suggesting that enhanced peptide binding to MHC class II molecules might depend
      on the fluidity of the cell membrane lipids.

PMID- 8258152
TI  - Clearance of recombinant vaccinia virus expressing IL-2: role of local host
      immune responses.
AB  - Recombinant vaccinia viruses that express the human or mouse IL-2 gene are
      rapidly eliminated from immunoincompetent nude mice whereas control viruses cause
      lethal infections. To understand the role that virus-encoded IL-2 plays in
      attenuation, we investigated the mechanism of virus elimination from nude mice.
      Survival correlated with accelerated clearance of the virus. Treatment of
      infected mice with antibodies to eliminate NK cells or to neutralize interferon
      gamma suggested that both are involved in the elimination of IL-2-producing
      virus. However, lytic activity of NK cells was not necessary as shown by studies
      with beige mice. Coinfection with IL-2-expressing and control virus resulted in
      lethal infection of nude mice, indicating the absence of significant systemic
      immunity. Focally acting immunopotentiating and chemotactic activities of virus
      encoded IL-2 and host-derived interferon-gamma seem to confer protection in this
      novel approach to virus attenuation.

PMID- 8258153
TI  - TNF receptor involvement in TNF-mediated activities against syngeneic malignant
      and normal mouse thymocytes.
AB  - Receptor-dependent tumor necrosis factor (TNF)-mediated activities against mouse
      thymoma cells and normal thymocytes syngeneic for C57 mice were examined to
      determine the specific involvement of TNF receptors R1 and R2. Both receptors are
      expressed by EL4 thymoma cells and normal C57 thymocytes. TNF-mediated activities
      included (a) cytotoxicity, (b) induction of hyposensitivity to TNF-mediated
      lysis, (c) costimulatory stimulation of thymocyte proliferation, and (d)
      activation of NF-kB-like transcription factor. The ability of polyclonal antisera
      against TNF receptors to mimic the above TNF-mediated activities was determined.
      The results clearly showed that anti-TNF-R1 antibodies were cytotoxic against EL4
      cells, induced hyposensitivity of S-EL4 to TNF lysis and activated the NF-kB-like
      transcription factor in EL 4 cells and syngeneic normal thymocytes. Antisera
      against TNF-R2 only mimicked TNF-mediated costimulation of thymocyte
      proliferation with IL2. No direct correlation was noted between TNF activation of
      NF-kB and TNF-mediated lysis.

PMID- 8258154
TI  - Mannoprotein-induced anti-U937 cell cytotoxicity in peripheral blood mononuclear
      cells from uninfected or HIV-infected subjects: role of interferon-gamma and
      tumor necrosis factor-alpha.
AB  - A mannoprotein fraction (MP-F2: mannan, > 90%; protein, 4.5%) from the human
      commensal microorganism Candida albicans was as efficient as interleukin-2 (IL-2)
      in generating cytotoxicity against the uninfected or human immunodeficiency virus
      type-1 (HIV-1) persistently infected monocytoid U937 cell line in cultured
      peripheral blood mononuclear cells (PBMC) from healthy human subjects. MP-F2
      activated killing of U937 cells (U937-MAK) decreased progressively with advancing
      stages of HIV-1 infection to virtually no killing effect in PBMC from advanced
      AIDS subjects (AIDS PBMC). This decrease paralleled a lowered susceptibility of
      U937 cells to natural killer cell activity. In contrast, IL-2-activated killing
      of U937 cells (U937-LAK) was not affected by the progression of HIV infection and
      persisted at high levels in AIDS PBMC. To shed light on the mechanisms of U937
      MAK and its decrease during HIV infection, IL-1 beta, IL-6, TNF-alpha, GM-CSF,
      and IFN-gamma production was analyzed. Decreases in TNF-alpha, GM-CSF, and IFN
      gamma, but not IL-1 beta or IL-6, levels were observed in MP-F2-stimulated PBMC
      from HIV-infected subjects, compared to healthy controls. Interestingly, these
      cytokine levels fell before the onset of AIDS. The greatest relative drop was
      that of IFN-gamma, from 4600 (+/- 600) to 290 (+/- 160) and 217 (+/- 110) mean
      pg/ml (+/- SE) in PBMC from healthy donors (11 subjects), CDC stages II + III (14
      subjects), and CDC stage IV (10 subjects), respectively. The following
      observations suggest that decreased IFN-gamma production plays a role in the
      abrogation of U937-MAK activity: (i) addition of neutralizing anti-IFN-gamma
      antibodies abolished both IFN-gamma and U937-MAK activity in PBMC from healthy
      subjects; (ii) substantial levels of IFN-gamma were detected in supernatants of
      PBMC cultures stimulated by IL-2, in line with preserved U937-LAK activity.
      Interestingly, anti-IFN-gamma antibodies also abolished TNF-alpha production, and
      the anti-TNF-alpha antiserum effect was comparable to that of anti-IFN-gamma in
      U937-MAK inhibition. In contrast, anti-TNF-alpha antibodies abrogated TNF-alpha
      activity, but only partially reduced IFN-gamma production. Thus, in human PBMC,
      U937-MAK activity progressively decreases with advancing stages of HIV infection,
      whereas U937-LAK activity is sustained. Furthermore, the present results indicate
      a pivotal role for IFN-gamma in U937 MAK activity, possibly through activation of
      TNF-alpha production.

PMID- 8258155
TI  - Bacterial phosphatidylcholine-preferring phospholipase C reversibly inhibits the
      membrane component of the NADPH oxidase in human polymorphonuclear leukocytes:
      implications for host defense.
AB  - Bacterial phosphatidylcholine-preferring phospholipase C (PC-PLC) has been
      recognized as a virulence factor and is implicated in the hemolytic and
      dermonecrotic properties associated with certain organisms. Moreover, recent data
      suggest that PC-PLC may be an important component in the signal transduction
      cascade by contributing to diacylglycerol (DAG) mass via the hydrolysis of
      phosphatidylcholine (PC). We have previously shown that PC-PLC can inhibit
      superoxide generation in human polymorphonuclear leukocytes (PMN). We now extend
      these observations and show that the mechanism of PC-PLC inhibition of superoxide
      generation is reversible inhibition of the membrane component of the NADPH
      oxidase (in a cell-free system) accompanied by expected generation of DAG and
      phosphorylcholine. Addition of PC reversed the effects of the enzyme.
      Surprisingly, we also found that phosphatidic acid (PA), the hydrolysis product
      of phospholipase D, was also produced in intact PMN following PC-PLC exposure.
      Subsequent addition of the agonist N-formylmethionyl-phenylalanine resulted in
      further PA production. Restoration of PA in cell-free preparations partially
      restored superoxide generating capability. We conclude that PC-PLC may enhance
      bacterial virulence by inhibiting superoxide generation by human PMN, and that
      this effect is due to direct inhibition of the membrane component of the NADPH
      oxidase.

PMID- 8258156
TI  - Role of macrophage tissue factor in the development of the delayed
      hypersensitivity reaction in monkey skin.
AB  - Delayed-type hypersensitivity (DTH) reaction is a cell-mediated immune response,
      characterized by fibrin deposition. To determine whether macrophage tissue factor
      (TF), an initiator of blood coagulation, was associated with the DTH reaction, TF
      expression on macrophages and resulting fibrin deposition at the site of DTH,
      induced in Bacille-Calmette-Guerin (BCG)-sensitized Japanese monkeys with
      intradermal administration of pure protein derivative of tuberculin (PPD), were
      examined immunohistochemically using monoclonal antibodies (MoAbs) against TF and
      fibrin. Most mononuclear cells, but not polymorphonuclear cells, in DTH reaction
      sites were TF-positive and were identified as macrophages by double
      immunostaining using anti-TF and anti-macrophage MoAbs. Fibrin deposition was
      only observed around TF-positive macrophages in the stroma of DTH reaction sites,
      and the deposition was not seen in the periphery of other TF-positive tissues
      (epidermis, trichoepithelium, and blood vessels). The development of induration
      and the extent of fibrin deposition paralleled an increase of TF-positive
      macrophages in the DTH reaction sites. In PPD-injected skin sites of
      nonsensitized monkeys, neither TF-positive macrophages nor fibrin were seen but
      epidermis, trichoepithelium, and blood vessels were TF-positive. Moreover, the
      development of induration was inhibited by simultaneous administration of anti-TF
      MoAb and PPD into BCG-sensitized monkeys. These results suggest that TF
      expression on macrophages in the reaction site is a key factor for the DTH
      reaction, through the activation of blood coagulation, resulting in fibrin
      deposition.

PMID- 8258157
TI  - Sequence of a prominent 16-residue self-peptide bound to HLA-B27 in a
      lymphoblastoid cell line.

PMID- 8258158
TI  - Antibody Targeted Photolysis.
AB  - The technique of Antibody Targeted Photolysis (ATPL) is reviewed from an
      historical perspective with a summary of the literature since the first
      experiments were performed in 1983. Attention is given to both the biological and
      photophysical properties of the various immunoconjugates that have been
      developed. References to critical discoveries and competing technologies in the
      photodynamic literature are given. Topics include: synthesis of immunoconjugates,
      in vitro vs. in vivo toxicity, in vivo biodistribution, immunoconjugate delivery,
      photosensitizer selection based on photophysical properties, light delivery for
      specific applications, oxygen requirements, and other physicochemical phenomena.
      A mathematical model of the dynamics for cell killing based upon the transport of
      phototoxins to the cell surface is developed. A generalized set of coupled
      differential equations is given, which conveniently summarizes the manifold
      requirements stressed earlier for successful cell killing. Solutions are then
      presented for an idealized set of conditions appropriate for an isolated tumor
      cell. Suggestions for further improvements and follow-up experiments are made
      that could help in the evolution of ATPL into a useful clinical therapy and/or
      probe for cell biological studies.

PMID- 8258159
TI  - Modulated release from drug delivery devices.
AB  - Modulated drug release devices are devices that are capable of adjusting drug
      output to meet a physiological need. Such devices can be broadly grouped as
      externally modulated and self-modulated. In the former case, an externally
      generated signal is applied to the device, which then adjusts drug output in
      response to the intensity of the signal. In the latter case, the changes in drug
      release are caused by changes in the environment surrounding the polymer and no
      external signal is necessary. Because of the real need for an improved treatment
      of diabetes, a significant portion of the research currently under way deals with
      the modulated release of insulin.

PMID- 8258160
TI  - [Experimental study and clinical application of oral administration of Chinese
      herb as an enema substitute].

PMID- 8258162
TI  - [Evaluation of training nurses for intensive care units].

PMID- 8258161
TI  - [Computer software used in analysis of nursing errors].

PMID- 8258163
TI  - [Assessing the quality of the activities of the scrubbing nurse in operating
      room].

PMID- 8258164
TI  - [Nursing care of pituitary prolactinoma with bromocriptine].

PMID- 8258165
TI  - [Nursing care of double channel catheter in femoral vein as temporary vascular
      path for hemodialysis].

PMID- 8258166
TI  - [Postoperative monitoring of pulmonary artery pressure in children in congenital
      heart disease with pulmonary hypertension].

PMID- 8258167
TI  - [Effect of various blood specimen collection methods on the determination of
      neonatal blood oxygen partial pressure].

PMID- 8258169
TI  - [Influence of hemodynamic changes during spine surgery in prone position and its
      nursing].

PMID- 8258168
TI  - [Treatment of allergic purpura nephritis with vincristine in children].

PMID- 8258170
TI  - [Factors influencing on serial checks of the vestibule function and related
      preparation].

PMID- 8258171
TI  - [Improving the hospital environment for clinical teaching].

PMID- 8258172
TI  - [Training for nurses on the use and care of catheterization].

PMID- 8258173
TI  - [A new form of nursing report].

PMID- 8258175
TI  - [Nursing assignments should be made according to position and title].

PMID- 8258174
TI  - [Topography of the points on the posterior aspect of the leg for intramuscular
      injection].

PMID- 8258176
TI  - [Standardized data items from the nursing units in nursing management].

PMID- 8258177
TI  - [Guide to self care of long-term hemodialysis].

PMID- 8258178
TI  - [Operating room nursing in surgery of intracranial neoplasms].

PMID- 8258179
TI  - [Pre and postoperative care of amnionic arthroplasty].

PMID- 8258180
TI  - [Nursing care of complications due to microwave in the treatment of liver
      cancer].

PMID- 8258181
TI  - [Nursing care of tuberculous meningitis in children with lateralis
      ventriculostomy].

PMID- 8258182
TI  - [Application of improved Hertz's eye surgical instrument].

PMID- 8258184
TI  - [Final examination reform on "basic nursing"].

PMID- 8258183
TI  - [Postoperative posture of patients with retinal perforation treated with
      pneumatic retinopexy].

PMID- 8258185
TI  - [Application of stereoscopic teaching method in nursing].

PMID- 8258186
TI  - [Our experience in initiating postgraduate nursing education course in our
      hospital].

PMID- 8258187
TI  - [Psychological effects on the bereaved].

PMID- 8258188
TI  - Normalisation of anti-cancer drug dosage using body weight and surface area: is
      it worthwhile? A review of theoretical and practical considerations.

PMID- 8258189
TI  - Combination treatment of cis- and carboplatin in cancers restricted to the
      peritoneal cavity in the rat.
AB  - In the present study, cisplatin (cDDP) and carboplatin (CBDCA) were combined in
      different in vitro and in vivo assays to determine whether combined cDDP and
      CBDCA treatment would eventually lead to a better antitumor response. Co
      incubation of CC531 cells with cDDP and CBDCA led to higher intracellular Pt
      concentrations (30.5 +/- 3.4 ng Pt/10(6) cells) than did cDDP (16.9 +/- 9.4 ng
      Pt/10(6) cells) or CBDCA (1.28 +/- 0.72 ng Pt/10(6) cells) incubation alone. In
      survival assays an additive cell kill was seen after combined treatment with cDDP
      and CBDCA. DNA binding experiments using isolated salmon-sperm DNA exposed to the
      drugs separately or in combination were in agreement with the survival studies
      (for cDDP a binding of 12.42 micrograms Pt/mg DNA; for CBDCA, 0.49 microgram
      Pt/mg DNA; and for combined CBDCA and cDDP, 12.9 micrograms Pt/mg DNA at 76 h).
      Toxicity studies in rats treated with cDDP plus CBDCA required a dose reduction
      for cDDP amounting to 20% of the MTD, whereas the CBDCA dose could be maintained.
      Pharmacokinetics studies showed higher AUCs and t1/2 beta in plasma as well as
      the peritoneal cavity after combined treatment with cDDP and CBDCA (both given
      i.p.) or following cDDP given i.p. and CBDCA given i.v. Pt concentrations in
      peritoneal tumors corresponded with these observations, with higher Pt
      concentrations following combined treatment than after single-agent injection. In
      addition, combined administration of cDDP i.p. and CBDCA i.v. led to higher Pt
      concentrations in peritoneal tumors than did administration of both drugs i.p.
      (3.93 +/- 0.9 vs 2.76 +/- 0.2 mg Pt/g tissue). The higher Pt concentrations in
      the peritoneal tumors after combined treatment was associated with a
      significantly better antitumor response in comparison with that observed after
      single-agent treatment (a growth delay of 30.2 +/- 5.6 days for cDDP i.p. plus
      CBDCA i.v. vs 16.1 +/- 5.4 days for cDDP alone and 10.8 +/- 4.2 days for CBDCA
      alone).

PMID- 8258190
TI  - Effect of cyclosporine on colchicine partitioning in the rat liver.
AB  - Colchicine is secreted into bile as a major pathway of elimination. Cyclosporine
      (CsA) inhibits colchicine biliary secretion. In the present study, the effects of
      cyclosporine and its vehicle (cremophor) on the partitioning of colchicine across
      the liver were studied. CsA decreased the colchicine bile/plasma ratio from 484
      +/- 39 to 53 +/- 3 (P < 0.001). This effect was due to both a decrease in
      bile/liver partitioning (control, 35.1 +/- 1.2, vs CsA treatment, 9.2 +/- 0.5; p
      < 0.001) as well as a decrease in liver/plasma partitioning (control, 13.7 +/-
      0.8, vs CsA treatment, 5.7 +/- 0.4; P < 0.001). Cremophor also decreased the
      colchicine bile/plasma ratio (317 +/- 19, P < 0.02 vs control), but this effect
      was due to a decrease in the liver/plasma ratio (9.99 +/- 0.7, P < 0.02 vs
      control) rather than the bile/liver ratio (31.9 +/- 2.1, P > 0.2 vs control).
      Inhibition at the canalicular membrane is consistent with the location of gp-170,
      the presumed transporter of colchicine.

PMID- 8258191
TI  - Antineoplastic activity and tolerability of a novel heterocyclic
      alkylphospholipid, D-20133.
AB  - Octadecyl-[2-(N-methylpiperidinio)ethyl]-phosphate (OMPEP, D-20133), a
      heterocyclic analogue of hexadecylphosphocholine (MIL), has been synthesized in
      an attempt to increase the therapeutic range of the parent compound. The
      antineoplastic activity of the novel alkylphospholipid was compared with that of
      MIL in dimethylbenz(a)anthracene-induced mammary carcinoma of the rat. Using
      tumors of different sizes and repeated daily doses as well as high single doses,
      we achieved marked remissions with either compound. However, the therapeutic
      range of OMPEP was broader than that of the parent drug. Furthermore, the emetic
      potential of OMPEP tested on ferrets was distinctly less pronounced than that of
      MIL. In vitro the new alkylphospholipid proved to be more active than MIL in all
      cell lines tested, and its differentiation-inducing capacity turned out to be
      superior to that of MIL. No hematological toxicity was observed at various OMPEP
      doses during a 3-week treatment period.

PMID- 8258192
TI  - Timing of treatment with ICRF-187 and its effect on chronic doxorubicin
      cardiotoxicity.
AB  - Studies were conducted to evaluate whether the timing of administration of ICRF
      187 [(+)-1,2-bis(3,5 dioxopiperazinyl-1-yl)propane] would influence the degree of
      cardioprotection provided by this agent against the development of doxorubicin
      induced chronic cardiomyopathy. Beagle dogs (8.5-14 kg) received either
      doxorubicin alone (1.75 mg/kg, i.v., n = 8), doxorubicin (1.75 mg/kg)
      simultaneously with ICRF-187 (35 mg/kg, i.v., n = 8), or doxorubicin (1.75 mg/kg)
      followed 2 h later by ICRF-187 (35 mg/kg, n = 8). Control animals received ICRF
      187 (35 mg/kg, n = 4) or saline (n = 4). All animals received a course of seven
      treatments, each given 3 weeks apart, and were killed 3 weeks after the last
      treatment. Semiquantitative grading of histologic sections of myocardium showed
      that as compared with animals treated with doxorubicin alone, the incidence and
      the severity of the doxorubicin-induced myocardial lesions were reduced in the
      two groups of animals given doxorubicin plus ICRF-187. However, protection was
      significantly better in dogs receiving ICRF-187 and doxorubicin simultaneously
      than in those given ICRF-187 2 h after doxorubicin. These observations were
      interpreted as indicating that the timing of administration of ICRF-187 with
      respect to that of doxorubicin is an important factor in determining the degree
      of cardioprotection and that there is a "time window" in which ICRF-187 exerts
      optimal effects.

PMID- 8258193
TI  - Assessing permanent damage to primitive hematopoietic stem cells after
      chemotherapy using the competitive repopulation assay.
AB  - The competitive repopulation assay was used to document the effects of six
      chemotherapeutic agents on primitive hematopoietic stem cells. The assay measures
      the relative abilities of donor cells to produce circulating erythrocytes and
      lymphocytes in lethally irradiated congeneic mice over a period of 6 months. Long
      lasting marrow reconstitutive deficits in cells of donor origin occurred after
      exposure to 5-fluorouracil (5FU), bis-chloronitrosourea (BCNU), cyclophosphamide
      (CTX), vincristine (VCR), and actinomycin D (ACT) but not after exposure to
      cytosine arabinoside (ARA). Repopulating abilities were reduced after as little
      as a single dose of CTX or BCNU. A second dose of BCNU caused even more severe
      effects. A single dose of 5FU had no effect on repopulating abilities despite a
      temporary 10-fold reduction in marrow cell number, but multiple doses reduced the
      marrow stem-cell replicative ability to less than half of the normal control
      levels. These effects were not reliably predicted or detected by colony-forming
      assays or by reductions in marrow cell number. Thus, long-lasting proliferative
      defects in the primitive hematopoietic stem-cell (PHSC) population can result
      from the use of chemotherapeutic agents. Such findings may have clinical
      implications, especially in individuals receiving repeated or prolonged
      administration of these agents or in instances of marrow transplantation.

PMID- 8258194
TI  - Modulation of antitumor alkylating agents by novobiocin, topotecan, and
      lonidamine.
AB  - Topoisomerase I and topoisomerase II allow a metabolically active cell to
      mobilize its supercoiled chromosomal DNA and undergo replication, transcription,
      recombination, and repair. Several topoisomerase inhibitors have recently been
      shown to be active in preclinical systems. Topotecan (SK&F 104,864), a water
      soluble camptothecin analog, is an inhibitor of topoisomerase I. Novobiocin is an
      inhibitor of topoisomerase II. Lonidamine depletes cellular adenosine 5'
      triphosphate (ATP) and may impede energy-dependent DNA repair, MCF-7 human breast
      cancer cells were treated in vitro with topotecan, novobiocin, and lonidamine
      alone, in paired combinations, and in combination with CDDP and melphalan. The
      three enzyme inhibitors alone and in combination did not increase tumor cell
      sensitivity to CDDP. However, the combinations of topotecan/novobiocin and
      lonidamine/novobiocin did enhance the cytotoxicity of melphalan. Mice bearing the
      FSaII fibrosarcoma were treated in vivo with topotecan, novobiocin, and
      lonidamine alone, in paired combinations, and in combination with CDDP,
      melphalan, BCNU, and cyclophosphamide. The combination of topotecan/novobiocin
      had the greatest impact on tumor cell sensitivity to each cytotoxic agent tested
      in both tumor cell-survival and tumor growth-delay assays. This sensitization was
      greatest at the highest concentrations of the cytotoxic agent tested.
      Combinations of topoisomerase I and topoisomerase II inhibitors may be useful as
      modulators of antitumor alkylating agents.

PMID- 8258195
TI  - Cytokinetic differences in the action of N-[2-(dimethylamino)ethyl]acridine-4
      carboxamide as compared with that of amsacrine and doxorubicin.
AB  - N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide dihydrochloride (DACA) is a
      topoisomerase II-directed DNA intercalator with high experimental solid-tumour
      activity. The effect of DACA on the cytokinetics of cultured Lewis lung
      adenocarcinoma cells was compared with those of two clinical drugs of this class,
      doxorubicin and amsacrine. Cells were exposed to drugs for a 1-h period at
      concentrations that reduced viability by approximately 99% as measured by
      clonogenic assays. Subsequent progress through the cell cycle was monitored by
      propidium staining of fixed cells and flow cytometry. DACA, amsacrine and
      doxorubicin did not inhibit the G1- to S-phase transition but did delay
      progression through the S-phase. The effect was maximal in the late S-phase and,
      because of the differential rates of progress of cells in various cycle
      positions, led to the development of a synchronous S-phase peak. This peak moved
      to the G2/M-phase position at 11 h after the removal of DACA or at 14 h after the
      removal of amsacrine or doxorubicin. The effects of the drugs on cells initially
      in the G2-phase was measured by scoring mitotic cells in the presence and absence
      of colchicine. DACA had an immediate inhibitory effect on the progression of
      cells from the G2-phase to mitosis. This effect was much greater for DACA than
      for the other two drugs, consistent with the greater effect of DACA on the G2/M
      phase to G1-phase transition. The results suggest that DACA causes cell-cycle
      changes expected for a DNA-damaging drug but differs from doxorubicin and
      amsacrine mainly by its effect on the transition of G2-phase cells to mitosis and
      the G1-phase.

PMID- 8258196
TI  - Treatment of subcutaneous and intracranial brain tumor xenografts with O6
      benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea.
AB  - O6-Alkylguanine-DNA alkyltransferase (AT) is a cellular protein that protects
      cells from the cytotoxic effects of nitrosoureas by repairing alkyl lesions at
      the O6 position of guanine. We have studied the ability of O6-benzylguanine to
      deplete AT activity in brain tumor xenografts and thereby increase the
      sensitivity of these tumors to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). In
      toxicity studies, pretreatment of athymic mice with O6-benzylguanine increased
      the toxicity of BCNU significantly. After i.p. injection of O6-benzylguanine into
      athymic mice carrying subcutaneous (s.c.) D341MED, a human medulloblastoma
      xenograft with a high AT activity, the AT activity of the tumors became
      undetectable within 1 h and remained depleted until 36 h. In s.c. xenografts to
      D341MED, treatment with O6-benzylguanine followed 1 h later by BCNU produced a
      significantly greater growth delay (14.8 days) than was seen with BCNU alone (2.3
      days). A lower pretreatment dose of O6-benzylguanine produced a significantly
      smaller therapeutic effect. Delaying the administration of BCNU until 36 h after
      O6-benzylguanine resulted in a growth delay (1.2 days) that was not significantly
      different from that produced by the control or BCNU alone. In athymic mice with
      intracranial (i.c.) xenografts of D341MED, pretreatment with O6-benzylguanine
      followed 1 h later by BCNU produced a significantly increased survival as
      compared with that of the control, BCNU alone, O6-benzylguanine alone, and O6
      benzylguanine followed 36 h later by BCNU. In experiments with s.c. xenografts of
      D245MG, a human glioma xenograft with undetectable AT activity, pretreatment with
      O6-benzylguanine 1 h prior to BCNU produced a significantly greater effect than
      was seen with BCNU treatment alone. The combination regimen, however, was not as
      effective as an equitoxic dose of BCNU alone. These studies suggest that O6
      benzylguanine may be a useful adjuvant to nitrosourea therapy in human
      malignancies that exhibit a range of AT activities and that dose and timing are
      important variables in achieving therapeutic success. These data also indicate
      that therapeutic potentiation of BCNU by O6-benzylguanine can be achieved in i.c.
      tumors. As a result, this approach may be useful in the treatment of neoplasms of
      the central nervous system.

PMID- 8258198
TI  - A limited sampling model for the pharmacokinetics of etoposide given orally.
AB  - A limited sampling model of etoposide after oral administration to estimate the
      area under the plasma concentration-time curve from 0 to 24 h (AUC) by
      determination of the drug plasma levels at only two time points was developed by
      a multiple regression analysis on a training data set of 15 patients receiving
      oral doses ranging from 54 to 90 mg/m2. The equation describing the model is AUC
      (micrograms ml-1 h) = 5.183 (micrograms ml-1 h) + 1.193 (h) x C1h (micrograms/ml)
      + 8.439 (h) x C4h (micrograms/ml) (R2 = 0.93, P = 0.0001), where C1h and C4h
      represent the plasma etoposide concentrations at 1 and 4 h, respectively. The
      model was validated prospectively on a test data set of 13 patients receiving
      oral doses ranging from 52 to 87 mg/m2 and, additionally, on a data set of 7
      patients receiving oral doses ranging between 176 and 200 mg/m2, investigated in
      a previous study. Validation on both test data sets gave a relative mean
      predictive error of 0.1% and a relative root mean square error of 15.8% and
      16.7%, respectively. The present study shows that it is possible to obtain a good
      estimate of the plasma AUC after oral administration of etoposide using a two
      time-point sampling model. The model can be used to monitor the etoposide AUC in
      patients receiving chronic oral treatment.

PMID- 8258199
TI  - Biliary elimination and pharmacokinetics of vinorelbine in micropigs.
AB  - The biliary elimination and pharmacokinetics of vinorelbine (NVB) were
      investigated in five conscious micropigs provided with a double-terminal
      choledocal fistula allowing the collection and reinstillation of bile. After the
      i.v. administration of NVB (0.5 mg/kg), serum and bile samples were collected
      over a 48-h period. The concentrations of NVB were measured by high-performance
      liquid chromatography. The serum concentrations decreased rapidly from a maximal
      value of 208.6 ng/ml (SD, 111.7 ng/ml). The mean half-life was 10.9 h (SD, 8.6 h)
      and the mean AUC0-48 h was 292.8 ng ml-1 h (SD, 79.4 ng ml-1 h). The bile
      concentrations were high, amounting to 16.0 micrograms/ml (range, 5.4-27.7
      micrograms/ml). The 0- to 48-h biliary excretion of unchanged NVB accounted for
      25.8% (SD, 5.7%) of the injected dose, with 21.5% (SD, 4.0%) being eliminated
      during the 0- to 8-h period. Desacetyl-NVB was found in an inconstant manner and
      in very low amounts in bile samples. In addition, no glucuronide of NVB could be
      detected. Thus, in the micropig, biliary excretion represents an important route
      of elimination for NVB.

PMID- 8258197
TI  - The effects of O6-benzylguanine and hypoxia on the cytotoxicity of 1,3-bis(2
      chloroethyl)-1-nitrosourea in nitrosourea-resistant SF-763 cells.
AB  - O6-Alkylguanine-DNA alkyltransferase (AGT) activity is associated with resistance
      of brain tumor cell lines to the cytotoxic effects of 1,3-bis(2-chloroethyl)-1
      nitrosourea (BCNU). SF-763 cells exhibit high AGT activity and are resistant to
      BCNU. In this study, we compared the effects of the AGT inhibitor O6
      benzylguanine (BG) on the cytotoxicity of BCNU in oxic and hypoxic SF-763 cells;
      we also measured AGT activity, ornithine decarboxylase (ODC) activity, and
      polyamine levels to determine if there was any correlation with cell survival as
      determined by colony-forming efficiency assay. Exponentially growing monolayer
      cells were pretreated with 10 microM BG for 2 h under oxic or hypoxic (95%
      nitrogen/5% CO2) conditions and then exposed to graded concentrations of BCNU for
      1 h. BG significantly lowered AGT activity but had no cytotoxic effect in oxic or
      hypoxic cells; hypoxia alone was not cytotoxic. The cytotoxicity of BCNU was 4
      times higher in BG-treated hypoxic cells than in oxic cells treated with BCNU
      alone; the BCNU doses required for a 1-log cell kill were 75 and 300 microM,
      respectively. ODC activity was lowered by hypoxia alone but was not significantly
      affected by BG in either hypoxic or oxic cells. Polyamine levels were not
      significantly affected by hypoxia or BG. These results indicate that pretreatment
      with BG dramatically lowers AGT activity and increases the cytotoxicity of BCNU
      in both oxic and hypoxic SF-763 cells. The mechanism of this enhanced
      cytotoxicity is apparently unrelated to ODC activity or polyamine levels.

PMID- 8258200
TI  - Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity
      in human liver microsomes.
AB  - The dextromethorphan-O-demethylase activity determined in human liver microsomes
      was used to screen various anticancer drugs for their ability to inhibit this
      cytochrome CYP2D6-dependent activity. Competitive inhibition indicates that the
      drug binds the enzyme and is potentially subjected to a polymorphic metabolism.
      Among the 13 anticancer drugs tested, 4 compounds caused competitive inhibition
      of dextromethorphan-O-demethylation: lomustine (Ki = 7.7 microM), doxorubicin (Ki
      = 75 microM), vinorelbine (Ki = 22 microM), and vinblastine (Ki = 42 microM). The
      results of these studies indicate that the metabolism of the drugs concerned is
      possibly altered in poor metabolizers of debrisoquine and requires further
      investigation to study their specific routes of biotransformation. The metabolism
      of these drugs probably involves various biotransformation pathways, among which
      the CYP2D6-dependent route would be of minor importance. A second hypothesis is
      that these drugs could be inhibitors of the isozyme without being a substrate.

PMID- 8258201
TI  - Acute mucocutaneous toxicity following high-dose hydroxyurea.
AB  - Three patients with advanced acute myeloid leukemia were treated with oral high
      dose hydroxyurea at a dose of 10 g daily for 8-10 days. Severe acute stomatitis
      developed in all three patients. In addition, two of the patients developed a
      peculiar acute cutaneous type of toxicity associated with soreness, violet
      erythema, and edema of the palms and foot soles followed by intense universal
      hyperpigmentation of the skin. Apparently, the pronounced acute mucocutaneous
      toxicity was caused by the sustained high daily dose of hydroxyurea, indicating
      that myelosuppression may not be the dose-limiting toxicity of this drug.

PMID- 8258202
TI  - The clinical value of screening chest radiography in the neonate with lung
      disease.
AB  - To examine the role of routine chest radiography in the management of the
      critically ill neonate with pulmonary disease, 41 term and preterm infants with
      lung diseases were prospectively evaluated. Seventy radiographs (35%) were
      obtained for clinical indications and 128 (65%) for prospective screening.
      Studies were compared with each infant's most recent previous study, if
      available. Every exam was designated Level I, if the radiograph identified a new
      finding that required clinical intervention; Level II, if an abnormality or
      interval change was observed that did not require immediate intervention; or
      Level III, if there was no interval change since the previous radiograph. Thirty
      three (47%) indication radiographs and 63 (49%) screening radiographs showed
      significant changes since the previous study. Twenty-four (34%) of the indication
      radiographs and 42 (33%) of the screening radiographs had Level I abnormalities
      (P = NS). Nine (13%) of the indication radiographs and 21 (16%) of the screening
      radiographs had Level II abnormalities (P = NS). Results suggest that routine
      screening chest radiographic studies are an important adjunct of care in
      critically ill newborns with respiratory disease and may identify potential
      problems before they are reflected in a change in clinical status.

PMID- 8258203
TI  - To x-ray or not to x-ray? That is the question.

PMID- 8258204
TI  - Predictors of mortality, morbidity, and disability in a cohort of infants < or =
      28 weeks' gestation.
AB  - This study attempted to identify predictors for mortality, morbidity, disability,
      and educational handicap at age 4 years in a cohort of 194 infants born at 23 to
      28 weeks' gestation at one regionalized tertiary center from 1983 to 1986. Forty
      one infants died (21%); standardized neurodevelopmental and functional
      assessments were conducted on 149 of 153 (97%) survivors at a mean age of 52
      months. Five significant predictors of death were identified with logistic
      regression analysis: gestational age 23 to 26 weeks, intraventricular hemorrhage
      grades 3 or 4, male gender, five-minute Apgar < or = 3, and absence of
      prophylactic calf lung surfactant extract. Significant predictors of
      neurodevelopmental morbidity included sepsis, male gender, and nonwhite race.
      Significant predictors of disability at age four included neurodevelopmental
      impairment and severe retinopathy of prematurity. Low socioeconomic status,
      nonwhite race and male gender were predictive of educational handicap. These
      findings suggest that outcomes may have distinct pathophysiologies. The role of
      biomedical events appears strongest for death.

PMID- 8258205
TI  - Is treatment of acute otitis media with once-a-day amoxicillin feasible? Results
      of a pilot study.
AB  - We report a study of the feasibility of once-a-day amoxicillin to treat acute
      otitis media (AOM). Seventy-seven children between ages 7 months and 12 years
      with AOM participated in a double-blind, placebo-controlled trial. Subjects
      received amoxicillin 40 mg/kg/day for 10 days. They were similar in age, sex,
      history of ear infections, and presenting symptoms. Group I received one total
      dose of amoxicillin and two doses of placebo daily. Group II received three
      divided doses of amoxicillin daily. Parents kept a daily diary of symptoms
      related to the child's illness and possible medication side effects. Ten children
      were lost to follow-up. In the remaining 67, pneumatic otoscopy and tympanometry
      after 10 to 14 days revealed that AOM had resolved in 82% of group I and 68% of
      group II. Groups showed no significant differences in persistence of middle ear
      effusion; 39% in group I and 24% in group II still had fluid. Diaries showed no
      significant differences between groups in medication side effects. Thus, reduced
      frequency dosing for AOM seems feasible and more realistic than current regimens.

PMID- 8258207
TI  - Anticipatory guidance for the adolescent. Parents' concerns.
AB  - Parents' opinions regarding anticipatory guidance for adolescents have not been
      adequately investigated. In this study, 932 parents of adolescents completed a
      computerized questionnaire listing 30 common psychosocial-medical concerns of
      adolescence. Respondents were asked how important it is for private pediatricians
      to discuss these topics with their teenagers during regular checkups. Ten items
      were rated important by > or = 90% of parents, 22 items by > or = 80%, and 29
      items by > or = 66%. Heeding parents' expectations and concerns, pediatricians
      should incorporate discussions of psychosocial-medical issues as a meaningful
      component of routine adolescent health care.

PMID- 8258206
TI  - Early transfer to a rehabilitation hospital for infants with chronic
      bronchopulmonary dysplasia.
AB  - Shortly after being weaned off the respirator, 43 infants with severe chronic
      bronchopulmonary dysplasia (BPD) were transferred from an intensive-care nursery
      at a teaching hospital to an affiliated children's rehabilitation hospital in a
      program that included special staff instruction. Morbidity, measured by rate of
      transfer back to the acute-care hospital, was lower than in a comparison group of
      15 infants treated for severe BPD during the previous two years. Average length
      of stay was significantly shortened and an average of $60,000 per patient was
      saved. Using a rehabilitation hospital as a step-down unit shifts the emphasis
      from acute needs to chronic and developmental needs and from intensive monitoring
      and nursing care to care given at home by parents with nursing assistance.

PMID- 8258208
TI  - Pediatric residency training: time for a change.

PMID- 8258209
TI  - Neonatal hyponatremic dehydration as an initial presentation of cystic fibrosis.

PMID- 8258210
TI  - Posterior fossa tumors presenting as meningoencephalitis.

PMID- 8258211
TI  - Henoch-Schonlein purpura followed by Wegener's granulomatosis.

PMID- 8258212
TI  - Facial trauma from a rigid infant pacifier face shield. A patient report and
      review of pacifier safety.

PMID- 8258213
TI  - Use of intravenous immunoglobulin in twin neonates with disseminated coxsackie B1
      infection.

PMID- 8258214
TI  - Benign paroxysmal torticollis presenting as "seizures" in infancy.

PMID- 8258215
TI  - Cardiac tamponade in an adolescent female: an unusual manifestation of systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) affects approximately 0.6 children per
      100,000. The disease is extremely rare in children under 5 years of age and is
      diagnosed predominantly in adolescent females. Children tend to present with more
      severe multisystem involvement than adults. Pericarditis occurs in approximately
      25% of patients with SLE in all age groups. Progression to tamponade is extremely
      uncommon in the pediatric population. In the current report, an adolescent girl
      is diagnosed with SLE after presenting with signs and symptoms consistent with
      cardiac tamponade. A review of other pediatric patients with a similar
      presentation is also included.

PMID- 8258216
TI  - A computerized medical record for clinical management of children with cerebral
      palsy.
AB  - Computerization has numerous applications in the administrative, business, and
      personal arenas. Applications in the medical field have produced a myriad of
      programs with varying degrees of impact on direct patient care. A recent
      Institute of Medicine report states that a computer-based medical record should
      become the standard for medical records.

PMID- 8258217
TI  - Staging of melanoma.

PMID- 8258218
TI  - The appearance of normal and abnormal arterial morphology on intravascular
      ultrasound.
AB  - The ultrasonic appearance of in vitro normal and atherosclerotic arterial wall
      was investigated with an intravascular ultrasound (IVUS) probe. Fresh cadaver
      specimens were used: two carotid, two aorta, four iliac and eight superficial
      femoral arteries. The wall of muscular arteries has a three-layered sonographic
      appearance. The central hypoechoic layer corresponds to the media, which is
      primarily composed of smooth muscle. Elastic arteries whose media have a high
      elastin content appear uniformly echogenic. Calcified plaque is strongly
      echogenic with acoustic shadowing, fibrous plaque is moderately echogenic, and
      where there is no cellular matrix the plaque is poorly echogenic. IVUS can
      provide information about internal plaque architecture. Three-dimensional
      reconstructions can be generated using a transputer-based workstation coupled to
      the transducer, providing detailed views of surface contour.

PMID- 8258219
TI  - Radiological and pathological features of AIDS-related polypoid cholangitis.
AB  - A review of the radiographs obtained at ERCP from 31 patients with AIDS-related
      sclerosing cholangitis (ARSC) demonstrated intraluminal polypoidal defects within
      the common bile duct and larger intrahepatic ducts in eight cases (26%). The
      radiological features from this subgroup are described and correlated with the
      microbiological and histological findings from biopsy specimens including two
      patients who underwent post-mortem examination. At microscopy the polypoid
      lesions were demonstrated to consist of granulation tissue. The presence of these
      polyps did not adversely affect the prognosis nor were they associated with any
      particular infective agent. We propose recognizing the existence of this entity
      by the term AIDS-related polypoid cholangitis (ARPC).

PMID- 8258220
TI  - Duplex Doppler measurements of the portal vein in portal hypertension.
AB  - In order to assess the validity of quantitative duplex Doppler measurements of
      portal vein flow, 10 patients with proven diffuse liver disease and portal
      hypertension were examined serially by two independent observers over a 3 month
      period. Multiple measurements of the portal vein were made using a consistent
      technique in an attempt to minimize observer errors. One patient proved
      unsuitable for ultrasound examination. In the remaining nine patients the intra
      observer portal vein measurements for one observer (19 paired examinations)
      correlated significantly for flow velocity (r = 0.80, P < 0.001) and derived bulk
      flow (r = 0.54, P < 0.02) but not for cross-sectional area (r = 0.27, P > 0.05).
      The intra-observer measurements for the second observer (11 paired examinations)
      were significantly correlated for cross-sectional area (r = 0.64, P < 0.05) and
      derived bulk flow (r = 0.61, P < 0.05) but not for flow velocity (r = 0.5, P >
      0.05). The inter-observer measurements (28 paired examinations) of the portal
      vein were all highly significantly correlated for cross-sectional area (r = 0.63,
      P < 0.001), flow velocity (r = 0.79, P < 0.001) and derived bulk flow (r = 0.73,
      P < 0.001). These results suggest that this quantitative Doppler technique may be
      valid for the serial study of portal vein flow in selected groups of patients
      with diffuse liver disease and portal hypertension.

PMID- 8258221
TI  - The ultrasound appearance of the normal psoas muscle.
AB  - One hundred and forty-four psoas muscles in 72 subjects were scanned to study the
      normal ultrasound appearance. For the purpose of description the psoas was
      divided into three sections. Ten of the 432 sections could not be adequately seen
      on ultrasound. The psoas demonstrated hyperechoic striations on a hypoechoic
      background typical of muscle. In addition the upper section, from the origin of
      the muscle to the lower pole of the kidney, contained echogenic planes in 15
      (10%) and the mid section, from the lower pole of kidney to iliac crest,
      demonstrated prominent echogenic planes and focal areas of increased and
      decreased echogenicity in 65 (46%). The lower section, from the iliac crest to
      fusion with the iliacus, demonstrated a single echogenic plane in 96 (70.5%)
      which was best seen running obliquely in the transverse plane and in 40 (29.5%)
      there were more complex echogenic planes or focal areas of increased or decreased
      echogenicity. The cause of the prominent echogenic plane in the lower section was
      not apparent in the anatomical literature and therefore cadaveric dissection of
      nine psoas muscles was performed which demonstrated that the echogenic plane was
      caused by intramuscular tendon fibres formed from the more cranial origins of the
      psoas. The psoas minor was not identified as a separate structure.

PMID- 8258222
TI  - Complex sclerosing lesions (radial scars) of the breast can be palpable.
AB  - Complex sclerosing lesion (CSL)/radial scar and carcinoma of breast can both
      present mammographically as stellate lesions. The mammographic features used to
      distinguish these two entities are reported as being unreliable. All reports to
      date indicate that CSLs are not palpable. Of the 54,407 women screened in the
      first 2 1/2 years of the Warwickshire, Solihull and Coventry Breast Screening
      Service, 24 histologically-proven CSLs were identified. This represents an
      incidence of 0.04%. In six (25%) of these patients a corresponding clinically
      palpable abnormality was identified. We found no imaging or histological features
      that differentiated the palpable lesions from the impalpable lesions. It is
      important not to assume that a palpable stellate lesion is a carcinoma.

PMID- 8258223
TI  - The computed tomographic appearances of angiosarcoma of the liver.
AB  - The computed tomographic (CT) appearances are described in five vinyl chloride
      workers with hepatic angiosarcoma subsequently confirmed at post-mortem. The
      tumour was multifocal in four patients. Non-enhanced scans were available in four
      cases showing hypodense masses relative to background liver. Dynamic scanning
      during intravenous contrast injection was performed in all five patients showing
      peripheral or central foci of enhancement within the tumour. On delayed post
      contrast scans performed in three patients the angiosarcoma became wholly or
      partly isodense compared to normal liver. The CT appearances of angiosarcoma of
      the liver are non-specific but are consistent with a vascular tumour, and the
      differential diagnosis is discussed. Due to the vascularity of angiosarcoma,
      liver biopsy may be hazardous and can be avoided when there is a history of
      exposure to vinyl chloride monomer and the CT findings are consistent with the
      diagnosis.

PMID- 8258224
TI  - MR findings of malignant melanoma of the vagina.
AB  - We report the MR findings in two cases of malignant melanoma of the vagina, one
      arising at the cervicovaginal junction which mimicked squamous cell carcinoma of
      the cervix and the other recurred in the vagina after previous resection. Two
      cases of malignant melanoma had high signal intensity on T1-weighted images and
      enhanced after gadopentetate dimeglumine administration.

PMID- 8258225
TI  - Azygos catheter placement as a cause of failure of dialysis.
AB  - Common complications of venous dialysis catheters include sepsis and accidental
      removal. Angiographic demonstration of dialysis lines is only rarely requested
      usually to confirm the presence of clot or stenosis as a cause for poor dialysis
      flow. Poor flow can also be due to inadvertent placement of the catheter in the
      azygos system. The use of dialysis catheters with a long venous limb which
      extends beyond the arterial port may predispose to such placement as their lumen
      is lateral to the central axis of the catheter. In those patients with poor
      venous access catheter placement under angiographic control may be helpful.

PMID- 8258226
TI  - Case report: unsuspected pericarditis diagnosed with gallium67 scan.
AB  - Gallium67 scanning may be used to localize disease activity in pyrexia of unknown
      origin. In this patient the finding of unsuspected pericarditis also provided a
      pointer to the correct diagnosis.

PMID- 8258227
TI  - Is the appendix where you think it is?

PMID- 8258228
TI  - Pseudoarthrosis complicating ankylosing spondylitis.

PMID- 8258229
TI  - Antibodies to topoisomerase II in idiopathic pulmonary fibrosis.
AB  - Antibodies to DNA topoisomerase II (anti-topoisomerase II) were detected by ELISA
      in the sera of 18 out of 41 (44%) patients with idiopathic pulmonary fibrosis
      (IPF). Follow-up sera were also obtained from 19 of the patients. DNA
      topoisomerase II binding remained constantly high or low in the majority of
      follow-up sera, but 2 out of the 8 positive cases became negative while 3 out of
      the 11 negative cases became positive during follow-up. No association was found
      between occurrence of anti-topoisomerase II antibodies and any indices of disease
      severity. Furthermore, individual patient follow-up did not show any correlation
      between changes in topoisomerase II binding and deterioration or improvement of
      clinical status. In conclusion our study shows that although anti-topoisomerase
      II are detectable in a large fraction (approximately 50%) of IPF patients and are
      useful for diagnostic purposes, they do not provide a measure of clinical
      activity.

PMID- 8258230
TI  - Tissue plasminogen activator, plasminogen activator inhibitor-1 and von
      Willebrand factor in rheumatoid arthritis.
AB  - Tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and
      von Willebrand factor (vWF), all of endothelial origin and active in the
      haemostasis, were analysed in 74 patients with rheumatoid arthritis. The
      concentrations were related to extra-articular disease and to the incidence of
      thromboembolic events (TE) registered in a 2-year follow-up period. Patients with
      extra-articular disease had a significant increase in PAI-1 activity and reduced
      tPA release in the venous occlusion test. von Willebrand factor, PAI-1 and also
      haptoglobin and triglycerides were significantly increased in the group of
      patients who later suffered from TE. In a multiple regression model, in which
      cholesterol, triglycerides and lipoprotein (a) showed significant association
      with TE, vWF had the strongest additive explanatory value. No distinct acute
      phase pattern of PAI-1 was found in any patient subgroup.

PMID- 8258231
TI  - Therapeutic effects of individual physical therapy in ankylosing spondylitis
      related to duration of disease.
AB  - Physical therapy in ankylosing spondylitis (AS) is considered important for
      maintaining or improving mobility, fitness, functioning, and global health. We
      studied the influence of disease duration on the short term effects of supervised
      individual therapy. One hundred forty-four AS outpatients (modified New York
      Criteria; mean age: 43 years; median duration of disease: 4 years; range: 0-33)
      received 12 supervised individual treatments in a 6-week course of 30 minutes.
      Endpoints were: spinal mobility (thoracic and lumbar flexion and extension, chest
      expansion, cervical rotation), fitness (maximum work capacity by ergometry),
      functioning (Sickness Impact Profile (SIP) and the Functional Index (FI)), and
      global patient assessment of change on a visual analogue scale. After 6 weeks
      patients had improved in all endpoints, but only significantly in rotation (8
      degrees, 10%), fitness (6 watt, 4%), and SIP (0.6, 14%; t-test, p < 0.05). Global
      patient assessment improved by 1.1 (22%). Plots of change scores and disease
      duration showed no evident relation. We also divided the population into two
      groups, with the median disease duration as a cut-off. No relevant difference in
      improvement was found between 'short duration' and 'long duration' groups (t-test
      of change scores, p > 0.05). In addition, no relevant correlation was found
      between change scores and disease duration (p > 0.01). It may be concluded that
      irrespective of disease duration, short term supervised individual therapy is
      effective in AS, slightly improving mobility, fitness, functioning and global
      health.

PMID- 8258232
TI  - Effect of therapy for thyroid dysfunction on musculoskeletal symptoms.
AB  - Our purpose was to assess the long-term effect of treatment for thyroid
      dysfunction on musculoskeletal symptoms. Forty-six patients (37 with
      hypothyroidism, 9 with hyperthyroidism), who visited the outpatient clinic of
      rheumatology and had abnormal thyroid function tests on their first visit,
      cooperated in the study. They were interviewed with a structured questionnaire
      about their past and current musculoskeletal complaints. Thyroid dysfunction was
      considered the only explanation for the original musculoskeletal symptoms in 24
      patients (Group I); in 19 patients an additional (rheumatological) diagnosis was
      made (Group II), and in 3 patients no apparent relation between musculoskeletal
      complaints and thyroid dysfunction was found. After treatment for thyroid
      dysfunction, the original complaints decreased in 52% and 47% of the patients in
      Group I and II, respectively. At the time of the follow-up study (mean follow-up
      duration 67 months) 91% of the patients had musculoskeletal symptoms, 80% of the
      patients said their present complaints were similar to their original symptoms.
      Treatment for thyroid dysfunction resulted in a temporary effect on
      musculoskeletal symptoms.

PMID- 8258233
TI  - Childhood systemic lupus erythematosus in songklanagarind hospital: a potential
      unique subgroup.
AB  - Twenty systemic lupus erythematosus patients under the age of 16 who had attended
      the Pediatric Department of Songklanagarind Hospital in the period 1985-1991 were
      reviewed retrospectively. The most common complaints were fever, alopecia, malar
      rash and oedema. The girl/boy ratio was 2.3/1. There were many unusual
      presentations such as Stevens-Johnson syndrome, psoriasis, rheumatoid nodules,
      papillitis and pseudotumor cerebri. Nephritis, haematological disorder and CNS
      involvement were found in 80, 50 and 35% respectively. All cases were positive
      for ANA. Sixty-five percent of cases had complications and mostly more than one.
      Common complications were infection, renal complication and side effects of
      chemotherapy. Five patients died because of renal failure, severe infections,
      cerebral infarction or GI bleeding.

PMID- 8258234
TI  - Anti-Sm: its predictive value in systemic lupus erythematosus.
AB  - The clinical manifestations of 131 rheumatic disease patients with anti-Sm
      antibody were studied. A variety of standard tests was utilized in the study,
      namely, the FANA test with mouse kidney as substrate for the assay of ANA, the
      Crithidia test for anti-double stranded DNA (anti-dsDNA) and double
      immunodiffusion for detecting antibodies to extractable nuclear antigens. The
      patients were grouped according to the presence of anti-Sm alone, or anti-Sm with
      some other antibodies. There were 17 with anti-Sm alone; 55 with anti-Sm+anti
      RNP; 15 with anti-Sm+anti-dsDNA; and 44 with anti-Sm+anti-RNP. The result of our
      study showed that although anti-Sm could be found in other diseases, it was
      exclusively detected in SLE only if anti-dsDNA was also present. Further, the SLE
      patients with anti-Sm alone had more frequent central nervous system
      manifestations than other groups of patients. The renal manifestation was
      observed more frequently in the group of SLE patients with anti-Sm+anti-dsDNA
      (92.9%). Among other major manifestations, haematologic involvement had a
      tendency to be less common in the group of patients with anti-Sm alone. The study
      concludes that the presence of anti-Sm antibody may be of some value to predict
      the clinical outcome.

PMID- 8258235
TI  - Incidence of Yersinia enterocolitica antibodies in patients with inflammatory
      joint diseases.
AB  - Agglutinating antibodies against Yersinia enterocolitica serotypes 0:3, 0:8 and,
      to a minor extent, 0:6 were found in 18 out of 93 patients with inflammatory
      joint diseases. Patients with undifferentiated arthritis showed the highest
      prevalence of antibodies against Yersinia enterocolitica. The possibility that
      serotypes other than 0:3 may be involved in triggering arthritis is discussed.

PMID- 8258236
TI  - One year treatment with low dose methotrexate in rheumatoid arthritis: effect on
      class specific rheumatoid factors.
AB  - We evaluated the effect of a one-year treatment of low dose methotrexate (MTX) on
      class specific rheumatoid factors in 27 patients with rheumatoid arthritis (RA).
      Enzyme-linked immunosorbent assay (ELISA) showed after 6 and 12 months a
      significant reduction of IgM-RF, IgA-RF and IgG-RF levels from the baseline
      values. During MTX treatment, changes of each RF isotype were not correlated with
      any other isotype and its corresponding immunoglobulin changes. Moreover,
      immunological changes were not related to the improvement of clinical parameters.
      Our results showed that low dose MTX can specifically affect levels of RF
      isotypes, which are involved in the immune pathogenesis of RA.

PMID- 8258237
TI  - Increased prevalence of spondylarthropathies in parents of children with
      pauciarticular juvenile chronic arthritis, type 1.
AB  - Using a standard questionnaire, parents of 70 children with type 1 pauciarticular
      juvenile chronic arthritis were asked about inflammatory back-pain. When the
      answer was positive, the parents were seen by a rheumatologist who used the
      preliminary criteria of the European Spondylarthropathy Study Group to decide
      whether the parent had spondylarthropathy or not. A diagnosis of
      spondylarthropathy was established in 6 out of 138 parents (4%). This is
      considerably higher than the expected prevalence of spondylarthropathy, which
      should not exceed 0.25%. This finding sheds a new light on pauciarticular JCA,
      type 1, since no adult counterpart has as yet been described.

PMID- 8258238
TI  - Architecture in cortical bone and ultrasound transmission velocity.
AB  - The square of ultrasound transmission velocity in a material is correlated to the
      modulus of elasticity, which is an indicator of its mechanical properties. This
      might make the measurement of ultrasound transmission velocity useful in the
      noninvasive diagnosis of bone diseases. Bone, however, is not an isotropic
      material but is architecturally structured. The aim of our study was to
      investigate and especially to quantify the influence of architecture in cortical
      bone on ultrasound transmission velocity. Twenty-two rectangular, flat specimens
      of cortical bone were prepared from diaphysis of fresh pig radius. Ultrasound
      transmission velocity was measured parallel and perpendicular to direction of
      Haversian channels. It was found to be 3647 +/- 41 m/s parallel to and 2821 +/-
      29 m/s perpendicular to Haversian channels respectively (p < 0.001). Our results
      clearly indicate that there is an important influence of architecture in cortical
      bone on ultrasound transmission velocity which has to be taken into account in
      its clinical use.

PMID- 8258239
TI  - Soluble CD4, CD8 in patients with polymyositis/dermatomyositis.
AB  - The concentrations of soluble CD4 (sCD4) and soluble CD8 (sCD8) were determined
      in 64 patients with polymyositis/dermatomyositis (PM/MD). The patients with PM/DM
      had significantly higher concentrations of sCD8, though the concentrations of
      sCD4 did not significantly increase. Patients with high concentrations of sCD8
      tended to have too high concentrations of soluble interleukin-2 receptor (sIL
      2R). The patients with high levels of myogenic enzymes tended to have high
      concentrations of sCD8. The results of a serial study indicated that the
      concentrations of sCD8 decreased simultaneously with the decrease of the myogenic
      enzymes. These results may suggest that the activation of CD8+ cells are related
      to muscular involvement.

PMID- 8258240
TI  - Circulating intercellular adhesion molecules-1 and autoantibodies including anti
      endothelial cell, anti-cardiolipin, and anti-neutrophil cytoplasma antibodies in
      patients with vasculitis.
AB  - Circulating intercellular adhesion molecule-1 (ICAM-1) and 3 types of
      autoantibodies were measured in 30 patients with angiographical or pathological
      proved vasculitis. There were 18 patients with systemic vasculitis and 12
      patients with cutaneous vasculitis. The measured antibodies included anti
      endothelial cell antibodies (AECA), anti-cardiolipin (ACL) antibodies of 3
      isotypes and anti-neutrophil cytoplasma antibodies (ANCA). The results showed
      that patients with systemic vasculitis had elevated levels of ICAM-1, AECA and
      IgG isotype antibody as compared with none or lower in patients with cutaneous
      vasculitis. Levels of ICAM-1 and IgG isotype ACL antibodies also decreased
      significantly after disease activity subsided in patients with systemic
      vasculitis. Measurement of ICAM-1 and autoantibodies may be useful in evaluating
      the extent of involvement and in following the disease activity of patients with
      vasculitis.

PMID- 8258241
TI  - Pregnancy outcome in women with antiphospholipid antibodies.
AB  - The association of antiphospholipid antibodies (APA) or lupus anticoagulant (LA)
      and recurrent fetal loss (RFL) is well established; however, the spectrum of
      pregnancy outcome in relation to various therapeutic approaches versus placebo is
      unknown. We studied 49 women with RFL, 14 with immune thrombocytopenia (ITP) 13
      of whom without a history of RFL, and 32 controls (all in the first trimester of
      pregnancy) for the presence of APA. Tests for APA were positive in 15/49 women
      with RFL (30%), 6/14 ITP (43%) and 2/32 controls (6%). Treatment in the APA
      positive patients consisted of: no treatment for the 8 patients who had no
      history of RFL (Group A; all 34 previous pregnancies successful), aspirin alone
      (Group B, 5 patients; all 30 previous pregnancies unsuccessful), aspirin with
      prednisolone (Group C, 9 patients; 69/80 previous pregnancies unsuccessful), or
      aspirin, prednisolone and immunoglobulin G for resistant cases (Group D, 4
      patients, previously in Group C). 10/11 (90.9%), 3/7 (43%), 7/13 (53.8%) and 4/7
      (57.1%) pregnancies were successful in Group A, B, C and D, respectively. There
      was a total of 19/45 (42%) failures including 3 pregnancies in one patient who
      failed to respond to all forms of therapy. This open study with small subgroups
      of patients draws attention to a wide range of pregnancy outcome in women with
      APA and to the fact that APA may serve only as a marker for a wide range of
      pathological conditions with variable degrees of disease severity. More studies
      are, however, needed to explore the real mechanism of RFL in women with APA and
      RFL, especially those who are resistant to therapy.

PMID- 8258242
TI  - Correlation of interleukin-2 receptor and neopterin secretion in rheumatoid
      arthritis.
AB  - In rheumatoid arthritis (RA) an immuno dysregulation alters the release of
      neopterin from human monocytes/macrophages, probably by activation of a feed-back
      regulation mechanism in pterin metabolism. With the overactivation of T
      lymphocytes, the secretion of interleukin-2 and its receptor (IL-2R) is
      influenced. Investigation on 84 RA patients has shown that this immunoactivation
      is accompanied by an increased secretion of neopterin and soluble IL-2R in the
      serum, and that both parameters are very suitable for detection of inflammatory
      disease activity. The significant correlation between neopterin and IL-2R (r =
      0.65; p < or = 0.001) in RA points out a possible connection in pathomechanisms
      of the immune system.

PMID- 8258243
TI  - Seronegative spondylarthropathy without spine involvement in Behcet's syndrome.
AB  - The case of a 49-year-old man affected by Behcet's syndrome (BS) without any
      clinical or radiological evidence of ankylosing spondylitis, exhibiting a
      peripheral enthesitis typical of seronegative spondyloarthropathy (SpA) is
      reported. The diagnosis of SpA is supported by computed tomographic evidence of
      sacroiliitis. This case confirms our hypothesis that patients with BS may have
      other forms of SpA than AS.

PMID- 8258244
TI  - Familial hypertrophic synovitis.
AB  - We describe here a 14-year old male patient with a life-long history of
      deformities of hands and feet, swelling of both knees and both wrists and limited
      motion of hips and elbows. His paternal aunt has similar findings. A two-month
      old brother developed flexion deformities of the hands similar to those of the
      patients.

PMID- 8258245
TI  - A case of anti-nuclear antibody negative systemic lupus erythematosus associated
      with penile ulcer.
AB  - We report here an old male patient with anti-nuclear antibody (ANA) negative
      systemic lupus erythematosus (SLE) with active renal disease and penile ulcer. He
      revealed nephrotic syndrome, malar rash and oral ulcer. SLE was discussed,
      however both ANA and anti-DNA antibody were persistently negative. A penile ulcer
      was also observed. He died of acute respiratory distress. Autopsy findings
      including onion skin lesion in the spleen and haematoxylin body in the kidney
      resulted in the final diagnosis of SLE. To our knowledge, association of penile
      ulcer with SLE has not yet been reported. Therefore, the present case is thought
      to be extremely unusual.

PMID- 8258246
TI  - Chronic leg ulcerations resembling vasculitis in two siblings with prolidase
      deficiency.
AB  - Two cases of prolidase deficiency in two siblings are presented. The patients
      complained of the typical clinical symptoms of the disease, including chronic leg
      ulcerations resembling vasculitis. They were mentally retarded, had typical
      facial characteristics, splenomegaly, and haematologic anomalies. Biochemical and
      morphological investigations confirmed the diagnosis. In these cases, alterations
      of the peripheral nervous system and decreased IgA levels were demonstrated for
      the first time.

PMID- 8258247
TI  - Interstitial lung disease and adult-onset Still's disease.
AB  - Adult-onset Still's disease is an uncommon rheumatological syndrome with a
      diversity of signs and symptoms. Pulmonary manifestations described are pleuritis
      and usually transient radiologic infiltrations. The patient presented in this
      case report had biopsy-proven lung fibrosis when adult-onset Still's disease was
      diagnosed. Three years after diagnosis, the patient developed clinical signs of
      the interstitial lung disorder. Radiological and histological progression was
      observed. Other causes of interstitial lung disorders were excluded. Clinicians
      should be aware that interstitial lung disease can be a complication of adult
      onset Still's disease and can compromise the clinical status of the patient.

PMID- 8258248
TI  - Isolated sternoclavicular joint arthritis in heroin addicts and/or HIV positive
      patients: three cases.
AB  - The authors describe three patients in whom septic arthritis of the
      sternoclavicular joint (SCJ) occurred, drug addiction and human immunodeficiency
      virus (HIV) infection representing the predisposing conditions. Infectious
      arthritis is well known in intravenous drug users, but it is rare in HIV positive
      patients, who are prone to bacterial infections from usual or unusual
      microorganisms. In one case, staphylococcus aureus methicillin sensitive was
      responsible for septic arthritis. In another case, SCJ infection was associated
      with pneumonitis.

PMID- 8258249
TI  - Autoantibodies in juvenile dermatomyositis.

PMID- 8258250
TI  - Scleroderma and motor neuron disease: an unusual association.

PMID- 8258251
TI  - ANCA associated with scleritis and sclerosing keratitis.

PMID- 8258252
TI  - New FDA policy encourages inclusion of women in clinical trials.

PMID- 8258253
TI  - New antiepilepsy drug, felbamate, marketed.

PMID- 8258254
TI  - Dosage of transdermal fentanyl.

PMID- 8258255
TI  - Pharmacologic prophylaxis of acute graft-versus-host disease after allogeneic
      marrow transplantation.
AB  - The immunology, pathophysiology, incidence, clinical manifestations, grading, and
      prevention of acute graft-versus-host disease (GVHD) are reviewed. GVHD occurs
      after allogeneic marrow transplantation when immunologically competent T
      lymphocytes in the donor marrow identify the host's antigens as foreign and
      attempt to reject host tissues. Acute GVHD occurs within three months after
      marrow transplantation and may affect the skin, gastrointestinal tract, liver,
      and immune system. Even with prophylactic immunosuppression, acute GVHD occurs in
      20% to 80% of patients. Moderate to severe GVHD (grades II-IV) is a major cause
      of morbidity and mortality after allogeneic bone marrow transplantation.
      Conventional GVHD prophylaxis consists of immunosuppressives such as
      corticosteroids, methotrexate, and cyclosporine. Methotrexate and cyclosporine
      are equally effective in preventing GVHD. A combination of both drugs is better
      than either drug alone and results in an improved survival rate. The addition of
      corticosteroids to methotrexate, cyclosporine, or antithymocyte globulin is also
      more effective than single-drug therapy. Serial administration of intravenous
      immune globulin may contribute additional protection against acute GVHD. There is
      conflicting evidence concerning the prophylactic efficacy of pentoxifylline.
      Elimination of T lymphocytes from the donor marrow before transplantation has
      been associated with less GVHD but a higher incidence of graft failure. Total
      elimination of GVHD in patients with leukemia may cause loss of a graft-versus
      leukemia effect, resulting in increased relapse rates and decreased long-term
      survival. Promising experimental prophylactic agents include thalidomide,
      zolimomab aritox, tacrolimus, antibodies to cytokines involved in the
      pathogenesis of GVHD, and monoclonal antibodies against cytokine receptors on T
      lymphocytes. Current research efforts are also directed toward eliminating GVHD
      without compromising the graft-versus-leukemia effect.

PMID- 8258256
TI  - Methotrexate for the treatment of chronic corticosteroid-dependent asthma.
AB  - The role and adverse effects of methotrexate in the treatment of chronic
      corticosteroid-dependent asthma are discussed. Methotrexate is a folic acid
      antagonist that has been used as an anti-inflammatory agent in the treatment of
      arthritis. It also appears to be effective in reducing the corticosteroid
      requirements in patients with chronic corticosteroid-dependent asthma, a use that
      was first reported in 1986. Studies of this use of methotrexate in adults support
      a trial of methotrexate in patients with severe asthma who have been unable to
      discontinue corticosteroid use despite aggressive management of their asthma and
      who are experiencing severe corticosteroid toxicity. Experience with methotrexate
      in children with asthma is limited to case series. Adverse effects associated
      with the use of methotrexate for treatment of corticosteroid-dependent asthma
      include nausea, elevated serum aminotransferase, diarrhea, and thinning of hair.
      While methotrexate appears to reduce corticosteroid requirements in patients with
      chronic corticosteroid-dependent asthma, its role in asthma therapy still needs
      to be clarified.

PMID- 8258257
TI  - Pharmacokinetics of mexiletine in middle-aged and elderly patients.

PMID- 8258258
TI  - Assay for midazolam in liquor folliculi during in vitro fertilization under
      anesthesia.

PMID- 8258259
TI  - Amiodarone-induced thyroid dysfunction.
AB  - Cases of hypothyroidism and hyperthyroidism associated with amiodarone therapy
      are described, and the mechanisms, clinical appearance, and management of
      amiodarone-induced thyroid dysfunction are discussed. A 72-year-old man with a
      history of recurrent ventricular tachycardia unresponsive to conventional
      antiarrhythmic drugs was started on amiodarone therapy. Initially he responded
      well, but after three months he began to have fatigue, dry skin, and intolerance
      of cold. His serum thyroid-stimulating hormone (TSH) concentration had risen from
      4.4 microU/mL before amiodarone therapy began to 20 microU/mL, consistent with
      hypothyroidism. He was started on sodium levothyroxine for thyroid hormone
      replacement; the dosage was adjusted in accordance with subsequent TSH
      measurements. His hospital course was complicated by congestive heart failure.
      The second patient was a 43-year-old man with a history of atrial fibrillation
      who developed hyperthyroidism when placed on amiodarone therapy. He had
      persistent sweating, intolerance of heat, restlessness, and tachycardia. Thyroid
      function tests confirmed the presence of hyperthyroidism. The patient was treated
      with propylthiouracil and propranolol, and amiodarone was discontinued. He
      remained unresponsive to the propylthiouracil, which was discontinued, and was
      scheduled for radioactive iodine treatment. The mechanism of amiodarone-induced
      thyroid dysfunction may involve the large iodine content of the drug. Amiodarone
      induced hypothyroidism may range in severity from mild symptoms to severe
      myxedema; the skin, hair, and nails are particularly affected. Persons with
      clinical hyperthyroidism secondary to amiodarone treatment show the signs and
      symptoms of a hypermetabolic state resulting from thyroid hormone excess.
      Amiodarone-induced hypothyroidism is treated with levothyroxine and
      hyperthyroidism with antithyroid drugs. Amiodarone can cause thyroid dysfunction,
      which can have serious consequences.

PMID- 8258260
TI  - Criteria for long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in
      adult inpatients and outpatients.

PMID- 8258261
TI  - Sepsis-bacteraemia and other infections due to non-opportunistic bacterial
      pathogens in a consecutive series of 788 patients hospitalized for HIV infection.
AB  - A retrospective study was carried out to evaluate the incidence, etiology and
      role of non-opportunistic bacterial infections in a series of 788 consecutive HIV
      infected patients hospitalized during the last 7 years; 71.9% of patients were
      i.v. drug addicts, 15.6% homo-bisexual men, 7.4% heterosexuals, 2.7%
      haemophiliacs and 2.4% children with vertically-acquired infection. According to
      the CDC classification of HIV infection, 71 patients were classified as CDC I-II,
      148 as CDC III, and 569 (72.2%) as CDC IV. Diagnosis of bacterial infection was
      based on signs and symptoms, in association with the isolation of microorganisms
      consistent with the clinical picture. Two hundred and nineteen patients out of
      788 (27.8%) (4 in CDC group I-II, 34 in CDC III and 181 in CDC IV), presented one
      or more episodes of non-opportunistic bacterial infection. The morbidity of these
      infections showed a significant correlation with the progression of HIV disease
      (CDC III vs. CDC I-II [p < 0.003] and CDC IV vs. CDC III [p < 0.05]), but no
      significant relation was found with age, sex or type of risk for HIV infection.
      The most frequent clinical picture was sepsis/bacteraemia (33.3%), followed by
      respiratory tract (23.8%), and genitourinary tract (20.8%) infections. A total of
      399 bacterial pathogens were isolated in 303 different episodes of infection: 211
      (52.9%) were gram-positive and 188 gram-negative, with Staphylococcus aureus (69
      isolations), Staphylococcus epidermidis (50), and Pseudomonas spp. (48) as the
      major pathogens. Sepsis/bacteraemia was the most frequent clinical picture
      associated with growth of gram-positive pathogens, while detection of gram
      negative bacteria appeared more significantly related with genitourinary or
      respiratory tract localizations. Bacterial infections in hospitalized HIV
      infected patients, even though rarely life-threatening, need particular attention
      because of the high incidence and recurrence rate, the wide aetiological and
      clinical spectrum, the frequent microbial associations and the strict
      relationship with the progression of HIV disease.

PMID- 8258262
TI  - [The pharmacological options for an immediate intervention in threatened
      premature labor].
AB  - The following preparations, with different mechanism of action, have been
      comparatively tested for induction of immediate tocolysis in case of threatened
      preterm labour: Hyoscine butylbromide, ritodrine, ketoprofen and the association
      of ritodrine with ketoprofen. Hyoscine butylbromide was found to be very easy to
      handle, but its myolytic effect is modest. Ritodrine and ketoprofen have shown a
      high and quantitatively similar tocolytic power. But even better results have
      been achieved with the association of ritodrine with ketoprofen which has shown a
      total myolytic effect. The authors suggest some hypotheses concerning the
      mechanism of action of these drugs, and some precautions for their correct
      clinical use.

PMID- 8258263
TI  - [The use of nimodipine in comatose patients with different types of
      cerebrovascular pathology].
AB  - The authors report on the use of nimodipine in 36 patients for coma due to severe
      cerebral (20 haemorrhagic, 2 ischaemic, 9 post-anoxic, 4 traumatic, 1 neoplastic)
      lesions. In addition to resuscitative therapy, all patients were given nimodipine
      per os, 60 mg every 4 hrs for 21 days. In all patients, survival, duration of the
      coma and degree of disability, according G.O.S., were evaluated. Decrease of
      mortality was highly significant, decrease of disability of surviving patients
      was significant if compared with comatose patients suffering from similar
      diseases, but not treated with nimodipine.

PMID- 8258264
TI  - [The parenteral administration of essential amino acids in patients on periodic
      hemodialysis treatment. A pilot study].
AB  - In an attempt to improve the nutritional status of seven hemodialysed patients,
      500 ml of a 5.5% nephrological essential amino acid solution (EAA) were
      administered during each dialysis session for 2 months. At the end of this
      treatment, a significant increase in albuminemia was found (p < 0.05). These
      results are an encouragement to continue this therapy, especially if it is kept
      in mind that the half-life of albumin is much shorter than the period of EAA
      administration.

PMID- 8258265
TI  - [The assessment of glucose tolerance in hypertensive subjects treated with
      amlodipine].
AB  - The authors studied the side effects of amlodipine on glucose metabolism,
      carrying out an oral glucose tolerance test before and after 8-10 days of
      treatment, in a group of subjects with normal glucose tolerance. No significant
      variation in the average plasma glucose and insulin levels was observed.
      Nevertheless, in some cases, during amlodipine therapy, a decrease in glucose
      plasma level was found.

PMID- 8258266
TI  - [The activity of misoprostol on the gastric and duodenal mucosal damage in
      patients with liver cirrhosis].
AB  - Twenty-five liver cirrhosis patients with endoscopically demonstrated gastro
      duodenal mucosal damage (microhemorrhages, erosions, ulcers) were treated with
      misoprostol (prostaglandin E1) 400 mg/die. Eleven patients (44%) had abdominal
      pain and diarrhea and stopped treatment. Three months later, a new endoscopy was
      performed in the 11 patients that completed the study (3 patients were lost at
      follow up). Mucosal damage was stable in 5 patients (45%) and improved in 6
      patients (55%), with complete absence of mucosal lesions in 2 patients (P =
      0.027, Wilcoxon Ranks test). No case of worsening was observed and no patient had
      digestive bleeding during treatment. Digestive bleeding is a common complication
      of liver cirrhosis, originating in about 50% of cases from gastro-duodenal
      mucosal damage. Misoprostol suggests itself as a possible alternative therapy to
      the drugs usually utilized in these lesions (beta-blockers, H2-inhibitors), but
      individual intolerance is frequent and must be preliminary excluded.

PMID- 8258267
TI  - [Taurodeoxycholic acid in the treatment of primary biliary cirrhosis. A
      controlled study in comparison to ursodeoxycholic acid].
AB  - Thirty patients with primary biliary cirrhosis were enrolled; 25 completed the
      study period (6 months). Of these, 12 were randomised to TUDCA treatment and 13
      to UDCA. Dosage range 12-15 mg/kg daily for both groups which were comparable at
      to age, sex, duration and stage of the disease, as well as for all liver
      laboratory tests. Altogether, the results obtained were satisfactory in both
      groups. What was surprising was that clinical experience failed to confirm the
      greater efficacy of TUDCA compared to UDCA. On the contrary, UDCA appeared to be
      more effective than TUDCA in improving liver function (even significantly so as
      far as GGT was concerned). Also with regard to tolerability, UDCA was definitely
      superior to TUDCA.

PMID- 8258268
TI  - [Images of hepatic parasitic cysts: echotomography, computed tomography and
      magnetic resonance compared].
AB  - Hepatic hydatic cysts are a very common finding in the endemic areas like
      Australia, the Middle East, New Zealand, South Africa and in some countries
      bordering the Mediterranean. Immigration has increased the finding of this
      pathology in some European and North American areas. Our purpose is to show
      possibilities and limits using US, TC and RM to demonstrate the presence of
      parasitic hepatic localizations and their evolution after therapy.

PMID- 8258269
TI  - [L-carnitine: from natural substance to endogenous drug].

PMID- 8258270
TI  - [A project for a registry of the history of obesity].

PMID- 8258271
TI  - [Jan Bedrna. 16 September 1897, Cesky Brod - 25 September 1956, Podebrady].

PMID- 8258272
TI  - [Transesophageal echocardiography in the evaluation of the atrial septum, the
      source of embolisms and ischemic heart disease in the intensive care unit].

PMID- 8258273
TI  - First dawnings.

PMID- 8258274
TI  - Development of the cardiovascular risk in the population of the Czech Republic.
AB  - Population surveys of the major cardiovascular risk factors were conducted in six
      districts of the Czech Republic in 1988 and 1992 as part of the WHO MONICA
      Project. One-percent independent random samples of the population aged 25-64
      years were examined and investigated; in 1988, the survey included 1357 men and
      1412 women (response rates of 85.5% and 88.4%, respectively); 1139 men and 1214
      women with the response rate 71.2% and 75.0%, respectively, were enrolled in
      1992. Over the four years, the mean levels of diastolic blood pressure rose from
      83.8 mmHg to 85.5 mmHg (p < 0.001) in men; the rise in women from 80.7 mmHg to
      81.6 mmHg was non-significant. Systolic blood pressure between the two surveys
      did not differ significantly. Mean total cholesterol levels declined from 6.24
      mmol/l to 5.91 mmol/l (p < 0.001) in men and from 6.16 mmol/l to 5.87 mmol/l (p <
      0.001) in women. Mean BMI decreased from 27.5 to 26.9 (p < 0.001) in men and from
      27.4 to 26.5 (p < 0.001) in women. The authors assume that the significant
      decreases in cholesterolaemia and BMI may be caused by changes in the dietary
      pattern resulting from the market economy principles setting in after the 1989
      revolution, and by an increased attention of the population to their health in
      the new socioeconomic conditions. If the trend continues, one might expect a
      decrease in mortality from IHD. On the other hand, the rise in diastolic blood
      pressure may be due to deteriorated control of hypertension.

PMID- 8258275
TI  - Percutaneous transluminal angioplasty of the deep femoral artery.
AB  - Percutaneous transluminal angioplasty (PTA) of the deep femoral artery (DFA) was
      performed in 21 patients with chronically occluded superficial femoral artery
      (SFA) and a significant DFA lesion as documented by arteriography. The authors
      failed to pass the guidewire through the occlusion in two patients. The results
      do not include another patient who, while the PTA was technically successful, had
      to have a limb amputated because of skin lesion infection. The remaining 18
      patients showed a significant increase in the ankle-arm pressure index,
      prolongation of the claudication interval and reported subjective improvement
      immediately after PTA; plethysmography performed in 14 patients revealed a
      significant increase in maximum foot blood flow. While the claudication intervals
      were found to have further significantly prolonged 6-12 months following PTA, the
      ankle-arm pressure index remained unchanged. There were no serious complications
      during and after the PTA procedure. In patients with both superficial and deep
      femoral artery involvement, where SFA PTA is not suitable or feasible, PTA of the
      DFA seems to be the method of choice. Considering its probable clinical benefits,
      it is appropriate to attempt it even in cases where the chances of technical
      success are low.

PMID- 8258276
TI  - Coronary angioplasty with monorail technique: experience in more than 2000 cases.
AB  - This article describes briefly the short- and long-term results of PTCA with
      monorail technique. From 1988 to 1992, 2183 out of a total of more than 4000
      patients have been treated with this technique. From these patients, a total of
      2693 vessels were dilated. Primary success was achieved in 93% of all attempted
      vessels, while the overall major complication rate of 3% was acceptable in this
      series. Although the primary success rates were comparable between patients with
      stable angina (n = 1288), unstable angina (n = 720), and acute myocardial
      infarction (n = 175), the major complication rate of 5.1% in patients with
      unstable angina was about twice of that in patients with stable angina. The long
      term clinical follow-up of a mean of 22 months was favorable with low mortality
      (2%) and infarction (6%) rates. However, an additional revascularization
      procedure (repeat PTCA or bypass surgery) was necessary in 19% of the patients
      due to restenosis. In conclusion, PTCA using the monorail technique can be
      performed safely and effectively in patients with either stable angina, unstable
      angina, or acute myocardial infarction.

PMID- 8258277
TI  - Hypoxaemic precordial ST mapping in the diagnosis of coronary insufficiency.
AB  - Hypoxaemic precordial ST mapping was compared with precordial exercise mapping in
      a group of 64 patients. During hypoxaemia, IHD patients show ischaemic changes in
      ST maps similar to those found in exercise maps, and a significant increase in
      the sums of ST depressions. The test can be recommended to detect coronary
      insufficiency in cases where the exercise ECG test is not feasible or available,
      and to expand the arsenal of non-invasive diagnostic procedures. The physical
      exercise test, however, remains the strongest test for ECG detection of
      myocardial ischaemia.

PMID- 8258278
TI  - [Hemodynamic effects of enoximone in patients with low left ventricular ejection
      fraction in surgery for ischemic heart disease].
AB  - Acute heart failure following cardiac surgery in extracorporeal circulation (EC)
      still poses a formidable problem requiring intensive pharmacological therapy and,
      often, also mechanical support. Preoperatively reduced left ventricular (LV)
      function raises the risk for the development of this complication. In their pilot
      study, the authors evaluated the haemodynamic effects of enoximone, a selective
      phosphodiesterase III inhibitor, administered at a dose of 1 mg/kg b.w. to 15
      patients with a preoperative LV ejection fraction < or = 35% 15 minutes before
      weaning from EC after an elective myocardial revascularization procedure. All
      patients were weaned from EC at first attempt without any problems and left the
      operating theatre in good condition. Enoximone administration led, in the
      monitored period (45 minutes after administration), to statistically significant
      increases in cardiac index (+68%; p < 0.01), oxygen supply (+75%; p < 0.01) and
      oxygen saturation in mixed venous blood (+10%; p < 0.1) and statistically
      significant decreases in pulmonary and systemic vascular resistance indexes (-52%
      and -48%, respectively; p < 0.001) and in oxygen extraction (-31%; p < 0.001).
      These changes were associated with decreases in central venous, mean pulmonary
      artery, and pulmonary capillary wedge pressure (n.s.). No serious side effects
      were seen, and the authors conclude enoximone can be the drug of first choice in
      high-risk patients following heart surgery in EC and requiring inotropic support.

PMID- 8258279
TI  - [The role of the myocardial interstitium in left ventricular remodeling after
      acute myocardial infarction].
AB  - An acute myocardial infarction (MI) is characterized by a change in the protein
      composition not only in the infarct area but, also, in the area not involved; the
      remodelling of cardiac tissue is the consequence of synthesis of qualitatively
      and quantitatively different collagenous and non-collagenous proteins. The
      authors discuss the biochemical and structural characteristics of extracellular
      space proteins (the main types of cardiac collagen include collagens I, III, IV
      and V, with an important role played by glycoproteins). The mechanisms involved
      in the alteration of the architecture of a left ventricle affected by an MI
      include the changed ratios of these proteins along with an effect on the
      structure and enzymatic activity of contractile proteins and myocyte slippage;
      these factors largely affect not only myocardial function but, also, the
      patient's prognosis. Despite a number of published data (mainly on the effect of
      ACE inhibitors), it is evident that the issue of controlling the quality and scar
      formation following an MI requires further study by clinical and experimental
      cardiologists.

PMID- 8258280
TI  - [Czech heart surgery in 1992].
AB  - A total of 163 operations in extracorporeal circulation per one million
      population (i.e., below 50% of the European average) were performed in the Czech
      Republic in 1992. While the most critical situation exists in the treatment of
      IHD, it is relatively favourable in the treatment of congenital heart defects. To
      improve the current state, it is imperative to recruit more nurses and to install
      better technology in medical facilities.

PMID- 8258281
TI  - [Invasive diagnosis of ischemic heart disease and percutaneous coronary
      angioplasty in the Czech Republic in 1992].
AB  - The rates of 450 diagnostic coronary angiographies and 60 PTCA procedures per one
      million population performed in the Czech Republic in 1992 are 30% of actual
      minimal need for the former, and 15% of the necessary PTCA procedures. The poor
      performance has an adverse effect on indication criteria as well as on the
      potential for timely interventions in patients with chronic IHD and, especially
      so, in patients with acute coronary events. To improve the current situation, it
      is critical to boost the throughput of the existing centres.

PMID- 8258282
TI  - Comparison of morphology and syntax in free narrative and structured tests:
      fluent vs. nonfluent aphasics.
AB  - Seven agrammatic Broca's and seven paragrammatic conduction aphasics were
      evaluated on a free narrative story elicitation test and on a structured, cross
      modal morphology and syntax battery (MSB). The latter permitted comparison of the
      same set of morphosyntactic forms in both production and comprehension. Results
      suggests distinctive oral production profiles, with agrammatics inferior to
      paragrammatics in use of auxiliaries, verb inflection and passive word order.
      Only agrammatics commonly omitted articles or main verbs. The use of noun plurals
      and possessives did not discriminate between the groups. The two groups did not
      differ in level of performance on MSB comprehension subtests, and the order of
      difficulty among the comprehension subtests was unrelated to their difficulty for
      production. This suggests that the source of agrammatic production errors is
      independent of comprehension errors. The production of targeted constructions on
      the MSB, an easily scored instrument, closely paralleled production in free
      narrative.

PMID- 8258283
TI  - Implications from aphasia for the syntax of null-subject sentences: underlying
      subject slots in Bulgarian.
AB  - Evidence for the existence of an underlying sentence-initial subject slot for
      Bulgarian null-subject personal constructions can be found in two aberrant
      tendencies by a Bulgarian patient with aphasia. In response to test sentences
      consisting of personal constructions that contained an object pronominal clitic
      and no lexical subject, the patient tended either to insert a superfluous
      sentence-initial pronominal subject, or to place the object pronominal clitic
      left-adjacent to the verb, in the position that it would have occupied had a
      sentence-initial overt subject been present.

PMID- 8258284
TI  - Emotion-related hemisphere asymmetry: subjective emotional responses to laterally
      presented films.
AB  - To investigate whether the cerebral hemispheres differ in their subjective
      emotional responses 54 adult subjects were presented two films of different
      emotion-related qualities (positive and negative film) either to their left or
      right hemisphere. The films were exposed by means of a technique for the
      lateralization of visual input that allows prolonged viewing while permitting
      free ocular scanning. Subjective emotional responses were assessed by means of a
      continuous rating of emotional arousal experienced during the movie as well as by
      retrospective ratings of ten different emotional qualities. Presenting both films
      to the right hemisphere resulted in stronger subjective responses in the
      continuous emotion rating as well as in some retrospectively assessed ratings
      compared to left-hemispheric presentation. The effects were more pronounced for
      the negative film. Taken together, the findings suggest a higher responsiveness
      of the right hemisphere in subjective emotional experience.

PMID- 8258285
TI  - Dense retrograde amnesia, intact learning capability and abnormal forgetting
      rate: a consolidation deficit?
AB  - Following a thoracic trauma, which caused brain hypoxia, a 24-year-old man
      presented with a dense retrograde amnesia for events, persons and environments
      that spanned his whole life before injury. Knowledge acquired at school or
      through the media were equally lost, with the exception of arithmetical skills
      and some geographical knowledge. No deficit was apparent in language, object
      recognition, motor skills and intellectual tests. Anterograde memory was marked
      by very efficient learning capacity, an almost perfect retention of information
      at delay interval of 4 hours and pathologically rapid forgetting at longer
      delays. Informal observations agreed with test performance in showing that he
      could relearn facts of the past and easily acquire new information, but tended to
      lose these memories if the information was not frequently rehearsed. PET showed a
      hypometabolism of the posterior temporal lobes. Though some points remain
      obscure, we propose that a consolidation deficit hypothesis provides the most
      sensible interpretation of this peculiar pattern of memory deficit.

PMID- 8258286
TI  - Preserved vocabulary acquisition in Down's syndrome: the role of phonological
      short-term memory.
AB  - We report the study of a 23-year-old Italian girl, FF, with Down's syndrome
      (trisomy 21). FF showed a remarkably good developmental acquisition of Italian
      language and vocabulary and was able to learn English and French, although the
      latter with less proficiency. FF showed an entirely preserved function of the
      phonological short-term store and articulatory rehearsal components of verbal
      short-term memory. By contrast, she was impaired in a wide range of tasks
      assessing verbal and non-verbal reasoning, visuo-spatial perception and memory,
      and verbal long-term memory. These findings, in line with evidence from brain
      damaged patients, normal subjects and children, suggest that phonological short
      term memory plays a crucial role in vocabulary acquisition, which may occur in
      the presence of substantial deficits of general intelligence and episodic memory.

PMID- 8258287
TI  - Recency judgements in Wernicke-Korsakoff and post-encephalitic amnesia:
      influences of proactive interference and retention interval.
AB  - This study further examines the performance of diencephalic and temporal lobe
      amnesics on the recency judgement task (Parkin, Leng and Hunkin, 1990). The two
      patient groups were represented by patients with Wernicke-Korsakoff syndrome
      (WKS) and post-Herpes simplex encephalitis (HSE). Experiment 1 demonstrated that
      poorer recency judgements by WKS patients were not due to a general proactive
      interference effect, but from an inability to remember which items had been
      designated targets on a given trial. Experiment 2 demonstrated that the superior
      performance of the HSE group was not attributable to a putative faster forgetting
      rate. In addition, the study found no relationship between recency judgements and
      degree of frontal lobe impairment. It is concluded that diencephalic damage has a
      particular effect on the ability to make recency judgements and that this
      represents a fundamental difference between diencephalic and temporal lobe
      amnesia. Theoretical interpretations of this difference are discussed.

PMID- 8258288
TI  - How to differentiate retrieval from storage deficit: a stochastic approach to
      semantic memory modeling.
AB  - Some of the methods currently used to differentiate retrieval from storage
      deficits in brain damaged patients are revisited. Indices based on association or
      agreement measures among the responses given by the subject on repeated trials,
      as well as direct estimates of storage and retrieval abilities based on crude
      percentages, are open to criticism. A simple Markov chain stochastic approach,
      which is free of the drawbacks of the other methods and which distinguishes
      storage from retrieval deficits more reliably and powerfully, is proposed.

PMID- 8258289
TI  - Diurnal type and hemispheric asymmetry.
AB  - Monk and Leng (1986) postulated that Morning-types (M-types) rely more than
      Evening-types (E-types) on subvocalization strategies, indirectly suggesting a
      difference in their habitual mode of hemispheric engagement. To evaluate this
      hypothesis, 48 right-handed women, 24 M-types and 24 age-matched E-types,
      performed verbal and spatial hemifield tachistoscopic tasks and recorded oral
      temperature at four separate times of day. Oral temperature curves were larger in
      amplitude and phase delayed for E-types. Reaction time curves were slower for E
      types, without M-E phase differences. Error rate curves showed significant time
      of-day effects at left-visual-field verbal tasks for M-types and at right-visual
      field spatial tasks for E-types, indicating a selective trend in relying on left
      hemispheric mode for M-types and on right hemispheric mode for E-types.
      Implications for circadian oscillatory control are discussed.

PMID- 8258290
TI  - Partial recovery from visual object agnosia: a 10 year follow-up study.
AB  - We describe a young woman, J.R., who sustained a very severe head injury in 1981
      at the age of 17 years. She was assessed in 1982 and found to have visual
      agnosia. Since then J.R. has been assessed on several occasions over a period of
      ten years. Her agnosia for real objects has resolved and she has improved on the
      identification of other classes of stimuli. However, she still has some problems
      with the identification of line drawings, photographs and model animals. Her
      drawing from memory remains particularly poor and she has difficulty with visual
      imagery. We consider her residual deficits in the light of Farah's (1990)
      theoretical framework; this proposes that associative agnosia could be due to a
      disconnection syndrome, a loss of stored visual representations or to the loss of
      knowledge of how to perceive objects. J.R.'s residual impairments appear to be
      mainly due to a loss of access to visual representations in the absence of visual
      input.

PMID- 8258291
TI  - The abstraction of a central tendency in amnesic patients.
AB  - Amnesic patients and control subjects were asked to reproduce arm movements of a
      given amplitude and to average amplitudes on series of three such movements. The
      error in averaging was found to be equal in patients and control subjects while
      reproduction performance was clearly affected by amnesia. The implications of
      these data for a theory of amnesia are briefly discussed.

PMID- 8258292
TI  - Unilateral contraction of facial muscles do effect emotions: a "failed
      replication's" failure to perform a replication.
AB  - Kop, Merckelbach and Muris (1991) reported a failure to replicate Schiff and
      Lamon's (1989) finding that unilateral muscle contractions induce emotions and
      influence cognitions in a manner which reflect those emotions. However, the
      procedures they used were different from the original experiment in substantive
      ways. These differences are described and it is explained how they account for
      the failure to replicate. This discussion helps illustrate the nature of the
      phenomenon which has been shown to be both robust and clinically relevant.

PMID- 8258293
TI  - Breast disease: the radiologist's expanding role.
AB  - The role of the diagnostic radiologist in breast cancer has expanded during the
      eight-decade history of breast imaging. The radiologist's role now encompasses
      both breast cancer diagnosis and treatment. This article traces the expansion of
      the radiologist's role through the history of mammography. The current roles of
      the radiologist in breast cancer diagnosis are discussed, including screening
      mammography in the asymptomatic patient, problem-solving breast imaging, breast
      ultrasound, and galactography. The radiologist's roles in breast cancer treatment
      that are discussed include preoperative needle localization, percutaneous breast
      biopsy, and evaluation of the postoperative breast.

PMID- 8258294
TI  - Chromosomal location and expression of the genes coding for Ku p70 and p80 in
      human cell lines and normal tissues.
AB  - Ku protein is a relatively abundant DNA-binding nuclear protein complex composed
      of two polypeptide subunits, p70 and p80. Ku has been recently identified as the
      regulatory component of the DNA-dependent protein kinase that phosphorylates RNA
      polymerase II. To further characterize in vivo regulation of Ku protein, we
      studied the expression of the transcripts coding for the Ku p70 and p80 subunits
      in different human cell lines and normal tissues by Northern blot hybridization,
      using specific cDNA probes. The expression level of both genes was approximately
      10-fold higher in established cell lines than in normal tissues. However, mRNA
      expression levels in permanent cell lines correlated more strongly with their
      proliferative state than with their level of malignant transformation. In
      purified T lymphocytes induced to proliferate by the combined action of
      monoclonal antibodies directed against the CD2 and CD28 adhesion molecules, Ku
      p70 and p80 mRNA steady-state levels increased as soon as 6 h after activation
      and lasted at least 72 h. The human genes coding for the Ku p70 and p80 subunits
      were localized by cytogenetic mapping, using fluorescence in situ hybridization,
      to 22q13 and 2q33-->q35, respectively.

PMID- 8258295
TI  - Seven genes on the short arm of human chromosome 3 map to two regions on Macropus
      eugenii (tammar wallaby) chromosome 2.
AB  - Seven genes were mapped by in situ hybridization to metaphase chromosomes of the
      marsupial species Macropus eugenii, using a series of human-derived cloned probes
      (six cosmids and one cDNA). The genes were located in two widely separated
      clusters on the long arm of M. eugenii chromosome 2, in contrast to their
      location in a single cluster on the distal half of the short arm of human
      chromosome 3. Multiple rearrangements had to be involved in the evolutionary
      divergence of these chromosome segments from the unknown arrangement in the
      common ancestor.

PMID- 8258296
TI  - Cloning and characterization of a fish centromeric satellite DNA.
AB  - A highly repetitive DNA sequence family from the genome of Sparus aurata has been
      cloned and characterized. The family is composed of repeat units of 186 bp in
      length, and it accounts for 2% of the fish genome. Data from Southern blots and
      in situ hybridization demonstrate that repeating units are tandemly arranged at
      the centromeres of all the chromosomes in this species. The repetitive sequence
      is AT rich (67%) and is characterized by short stretches of consecutive AT base
      pairs and by short direct and inverted repeats. Sequence analysis of six cloned
      monomers of the family reveals some variation among clones at random positions
      and also distinguishes two subfamilies of repeats that differ in a highly
      divergent block of 31 bp. These two subfamilies do not seem to be located in
      separate domains but occur together in the centromere of each chromosome pair.
      The presence of this repeat family in the genome of other Sparidae species, some
      of which are relatively distant from S. aurata, indicates that this repetitive
      sequence could be an important component of the centromere in this fish family.

PMID- 8258297
TI  - Characterization of a human chromosome 4 flow-sorted cosmid library.
AB  - A cosmid library has been constructed from a hamster x human hybrid cell line and
      gridded into 270 microtiter plates containing a total of 25,920 single colonies.
      Approximately 84% of the recombinants contain human material, with an average
      length of 29 kb. This library represents a nearly three-fold coverage of human
      chromosome 4. We investigated this library for presumptive genes, using a set of
      oligonucleotides detecting SpI and splice-site consensus sequences. The presence
      of simple repeat motifs was investigated in the cosmids using the
      oligonucleotides (GGATTT)3, (GGAT)4, (CAC)5, (GCC)5, (AGC)5, (GATA)4, (GACA)4,
      and (CA)8 as hybridization probes.

PMID- 8258298
TI  - Chimpanzee Rh-like blood group genes map to chromosome region 1p36.1-->p34.2 by
      in situ hybridization.
AB  - A human Rh cDNA probe was used to map the Rh-like genes in the chimpanzee. The
      data gathered made it possible to uniquely localize these genes to chimpanzee
      chromosome region 1p36.1-->p34.2. This chromosomal localization is homologous to
      the location of the Rh genes in the human genome.

PMID- 8258299
TI  - Demonstration of the X-linkage and order to the genes GLA, G6PD, HPRT, and PGK in
      two vole species of the genus Microtus.
AB  - Using a variety of genetic methods, it is shown in this paper that the genes GLA,
      G6PD, HPRT, and PGK are X-linked in the vole Microtus subarvalis. The order of
      these genes has been investigated in two vole species, M. subarvalis and M.
      kirgisorum, by using the mapping technique of Goss and Harris (1977a, b), which
      depends on the analysis of gamma-ray-induced gene segregation. The experimental
      data were processed with the computer programme RHMAP (Ginsburg et al., 1993).
      The analysis indicated that the correct gene order in M. subarvalis is PGK-HPRT
      G6PD-GLA, and the same gene order was found to be the most probable for M.
      kirgisorum. The relative distances between the genes in the two vole species are
      apparently the same. The RHMAP programme has also been applied to data previously
      reported for the same set of X-linked genes in the American mink (Zhdanova et
      al., 1988), the Australian marsupial Planigale maculata (Dobrovic and Graves,
      1986), and man. The evolutionary conservation of the linear order of these X
      linked genes in different mammalian taxa is discussed.

PMID- 8258300
TI  - Molecular analysis of a human Y;1 translocation in an azoospermic male.
AB  - Cytogenetic studies on an azoospermic male revealed a balanced Y;1 translocation:
      46,X,t(Y;1)(q12;p34.3). In situ hybridization with the probe St35-239 (DXY64) and
      with a probe detecting telomeric sequences revealed that only the Y telomere is
      involved in the translocation. Fluorescence in situ hybridization with a
      chromosome 1 library on meiotic preparations revealed consistent contact of the
      painted chromosome 1 with the sex vesicle at pachytene, the most advanced stage
      of spermatogenesis observed. No deletions were observed after Southern blot
      analysis with probes p49f (DYS1), 50f2 (DYS7), and 52d (DYF27), which map in
      interval 6 of the Y chromosome, which includes the azoospermia factor (AZF) gene.
      The results indicate that the infertility of the translocation carrier could be
      due to an alteration of the sex vesicle structure or to a disturbance of X
      chromosome inactivation as a result of the proximity to the autosomal portion.

PMID- 8258301
TI  - Assignment of the human skeletal muscle alpha actin gene (ACTA1) to 1q42 by
      fluorescence in situ hybridisation.
AB  - The human skeletal muscle alpha actin gene (ACTA1) has previously been localized
      to 1p21-->qter using somatic cell hybrids and a specific probe from the 3'
      untranslated region of the gene. Using fluorescence in situ hybridization the
      localization has been confirmed and the ACTA1 gene precisely mapped to 1q42.

PMID- 8258302
TI  - Intragenic reorganization of RB1 in a complex (4;13) rearrangement demonstrated
      by FISH.
AB  - Reciprocal chromosome translocations with no apparent loss of material are the
      most common de novo structural rearrangements in man. The large majority of these
      cases have been characterized cytogenetically but very few have been investigated
      at the molecular level. Using fluorescence in situ hybridization (FISH) we have
      studied the organization of the tumor suppressor gene RB1 in a patient with
      retinoblastoma and a rearrangement between chromosomes 4 and 13. In addition to
      the hybridization signal on the normal chromosome 13, three distinct sites of
      hybridization of RB1 probes on the translocated chromosomes were detected. These
      findings show that a complex rearrangement occurred involving at least three
      breaks on chromosome 13, two of them in the RB1 gene. This also demonstrates that
      FISH, which offers resolution between that of fine molecular methods and
      classical cytogenetics, is a valuable tool for investigating organization of
      sequences at breakpoints of chromosomal rearrangements.

PMID- 8258304
TI  - The human gene for nuclear protein BM28 (CDCL1), a new member of the early S
      phase family of proteins, maps to chromosome band 3q21.
AB  - BM28, a newly recognized human nuclear protein, possibly plays an important role
      in two crucial steps of the cell cycle e.g. the onset of DNA replication and cell
      division. It shows significant similarity to members of a recently defined family
      of early S-phase proteins. Using total plasmid DNA containing the complete coding
      sequence of the BM28 gene (CDCL1, for cdc-like 1) as a probe for fluorescence in
      situ hybridization, we have mapped the gene to chromosome band 3q21. This region
      is involved in specific structural chromosome aberrations found in acute myeloid
      leukemia (AML). Based on the function of BM28 and the chromosomal location of its
      gene, CDCL1 might prove to be a candidate for an oncogene affected by the
      chromosomal breaks and playing a pathogenetic role in AML.

PMID- 8258303
TI  - Identification of a marsupial OTF1 gene: cross-species STS analysis and in situ
      cross-hybridization to Macropus eugenii chromosomes 3/4 and 5.
AB  - The ability of the human octamer-binding transcription factor 1 (gene symbol:
      OTF1) sequence tagged site (STS) marker to identify cross-species gene homologues
      has been assessed using the marsupial Macropus eugenii genome. Two regions of
      sequence homology with human OTF1 have been located on M. eugenii chromosomes 3/4
      and 5 by in situ hybridization. These regions are likely to represent cross
      reaction with the homologues of human OTF1 and closely related OTF2 genes.

PMID- 8258305
TI  - Is X-Y recombination necessary for spermatocyte survival during mammalian
      spermatogenesis?

PMID- 8258306
TI  - The diabetic foot: aetiopathogenesis and management.

PMID- 8258307
TI  - Alcohol, glucose metabolism and diabetes.

PMID- 8258308
TI  - Management of diabetes in pregnancy.

PMID- 8258309
TI  - The role of DQ alpha-beta heterodimers in genetic susceptibility to insulin
      dependent diabetes.

PMID- 8258310
TI  - Diet and diabetes.

PMID- 8258311
TI  - [Changes in the heart rhythm studied by the PWC170 test following physical
      loading].
AB  - By application of the two-component test PWC170, the changes in the heart rate
      (HR) and the difference in the duration of the minimal and maximal cardiac cycles
      (SAr), were studied. The indices (HR and SAr) were recorded by
      electrocardiography prior to the test (initial values), during the three-minute
      pause between the two loadings and in the three-minute recovery period following
      the second loading. It was found that SAr in the pause after the first loading
      with lower intensity of the test was more markedly expressed with respect to its
      initial values, while in the recovery period after the more intensive second
      loading of the test it was not only less expressed but in a number of cases did
      not reach the initial values. It was assumed that the relationship between the
      expressed in each moment influences of the vagal and sympathetic neuroregulatory
      mechanisms of the heart was significant for the expression of the observed
      rhythmic fluctuations.

PMID- 8258312
TI  - [The effect of anionic complexes on cytochrome c oxidation by cytochrome c
      oxidase].
AB  - The effect of different buffer anions on the maximal velocity (Vmax) and
      Michaelis constant (Km) of the first reaction between horse cytochrome c and beef
      cytochrome c oxidase was studied. The Michaelis constant for the high affinity
      phase varies little as the buffer anions borate, phosphate, succinate and citrate
      were employed, but Vmax varies significantly. At the ionic strength I = 0.1 and
      pH 7.4 the Vmax increases in the order as following: borate < phosphate <
      succinate < > citrate. citrate. The differences in maximal activities in the
      presence of the anions may result from the changes in anion binding side on
      cytochrome c that affect its interaction with cytochrome c oxidase. The effect of
      the phosphate, succinate and citrate anions on the electron transfer reaction
      between cytochrome c and cytochrome c oxidase is important as a control of the
      respiration process in mitochondria at physiological conditions.

PMID- 8258313
TI  - [The sperm-agglutinating activity of the fractions of saline root extracts from
      Arum maculatum].
AB  - Our previous investigations have demonstrated that saline extract of Arum
      maculatum contains lectin (sperm agglutinin) which agglutinates human ejaculated
      spermatozoa of the type tail to tail and head to tail. By means of speed liquid
      chromatography (Mono S XP 5/5) eight fractions (I-VIII) were obtained. The sperm
      agglutinating activity of the fractions was investigated against frog testicular
      spermatozoa and testicular and epididymal spermatozoa of man, rabbit, rat and
      mouse. The fractions did not agglutinate frog spermatozoa. Fraction I
      agglutinated rabbit, rat and murine spermatozoa; fraction II-rabbit and rat
      spermatozoa; fraction VII-only human spermatozoa, and fraction VIII-human, as
      well as animal spermatozoa. The fractions III, IV, V, VI had no sperm
      agglutinating activity. These data could be explained by the assumption that the
      differences in the sperm-agglutinating activity of the fractions are due to
      isoforms (called also isolectins) of the phytospermagglutinin, contained in the
      saline extract of Arum maculatum.

PMID- 8258314
TI  - [The microcomputer study and processing of the values of the blood pressure and
      intersystolic interval in laboratory animals].
AB  - A system is created for study of the agents, affecting the arterial pressure and
      baroreflectory sensitivity, which comprises:transducer for arterial pressure
      Statham P23 ID, connected to a polygraph Biomedica O.T.E.; eight-bite analogous
      numerical transformer; microcomputer, compatible to Apple 2+; two diskette
      devices and printer. The arterial pressure of the lab animals (rats, rabbits,
      cats) is directly measured in a. carotis communis by means of the transducer and
      is recorded on the polygraph. For the system a computer program is designed which
      allows archivation of the primary experimental data; automatic and precise
      determination of the momentary values of the systolic and diastolic arterial
      pressure and intersystolic interval; determination of the baroreflectory
      sensitivity by means of linear regressive analyses; printing of the results under
      the form of diagrams and tables. By means of this system much time is spared,
      related to the accounting and handling of the experimental data.

PMID- 8258315
TI  - [Methemoglobinemias. Cytochrome b5-reductase deficiency].
AB  - In the paper are considered the basic mechanisms, leading to accumulation of
      methemoglobin in the red blood cells. The inherited methemoglobinaemia, due to
      enzymatic failure of cytochrome B5-reductase is considered.

PMID- 8258316
TI  - [Problem solving of the clinical case-method type for the development of clinical
      thinking. The illustrative problem of galactosemia].
AB  - Problem-solving case approach is an effective method for teaching clinical
      concepts. This method makes medical students be aware of the significance of
      Biochemistry for the clinical practice. The students are stimulated to study
      basic biochemical principles. The complete text of a problem case on galactosemia
      is presented. This case, usually given to the students during the final seminar
      on carbohydrate metabolism reflects a real situation, in which the student feels
      responsible to make decisions. He has to make the diagnosis and prescribe a
      treatment. The student's actions are assessed and commented. The students took a
      great interest in that problem case and that shows that it is possible and
      necessary even in the second preclinical year to joint the theoretical principles
      with the future clinical practice.

PMID- 8258317
TI  - [The facilitation and inhibition of monosynaptic reflexes in the upper extremity
      of nursing infants].
AB  - The upper extremity H-reflex was investigated in healthy children, aged from 3 to
      15 months. The electromyographic reflex responses of m. abduct or digiti min. and
      m. flexor carpi uln. were registered after electric stimulation of n. ulnaris. We
      constructed the curve of restoration of H-reflex after application of a couple of
      stimuli with equal duration and intensity, but over increasing intervals. We
      established changes in the excitation of H-reflex, obtained from m. flexor carpi
      uln., by increasing of the interval between the conditional and test stimuli. In
      the interval of 5 ms maximal facilitation was registered, while in the interval
      of 20 and 30 ms-maximal inhibition. In children aged from 3 to 9 months with
      persisting H-reflex in m. abductor digit min. we established possibility for its
      complete inhibition after application of a couple of stimuli with interval of 20
      ms. In children aged from 9 to 15 months with vanished H-reflex in m. abductor
      digiti min. possibility for its obtaining was established after application of a
      couple of stimuli with interval of 5 ms. Quotation is made of evidences in favour
      of the hypothesis for the functional character of the disappearance of H-reflex
      in the small muscles of the arm in the first year of life of the children.

PMID- 8258318
TI  - Analysis of tetanus toxin peptide/DR recognition by human T cell receptors
      reconstituted into a murine T cell hybridoma.
AB  - We have previously reported that human T cell receptors (TcR) selected in the
      class II-restricted (HLA-DRB1*1302) response to a tetanus toxin peptide (tt830
      843) frequently used the V beta 2 germ-line segment which paired with several V
      alpha segments and that the putative CDR3 of both alpha and beta chains showed
      remarkable heterogeneity. To analyze the structural basis for recognition of the
      tt830-843/DR complex, five of these TcR were reconstituted into a murine T cell
      hybridoma, 58 alpha- beta-, by expressing the human alpha and beta variable
      regions joined to the mouse alpha and beta constant regions, respectively. The
      chimeric TcR, expressing the same V beta germ-line segment (V beta 2), two
      expressing V alpha 21.1, two V alpha 17.1 and one V alpha 8.1 were shown to have
      the expected antigen specificity and DR restriction. Two lines of evidence
      suggested that the putative CDR3, although not conserved in these TcR, played a
      key role in recognition. First, two TcR with identical V germ-line segments but
      distinct CDR3 showed large difference in their capacity to react with the ligand.
      Second, interchanging the alpha and beta chains from tt830-843/DR1302-specific
      TcR which differed in their CDR3 sequences invariably led to loss of recognition.
      We also asked whether germ-line V alpha 17.1 could functionally replace V alpha
      21.1, as they appear to be related in their primary sequence. However, as in the
      case of CDR3 exchanges, V alpha replacement abrogated TcR reactivity. Taken
      together, these data underline the fine interdependence of the structural
      components of the TcR binding site in defining a given specificity. Four of the
      TcR studied displaying promiscuous recognition were also tested against different
      DR alleles and site-directed mutants. The results of these experiments suggested
      that, in spite of their structural heterogeneity, anti-tt830-843 TcR may have a
      similar orientation with respect to the peptide/DR complex. The reconstitution
      system described herein should represent a valuable tool for detailed studies of
      human TcR specificity.

PMID- 8258319
TI  - Allergy-associated I epsilon and Ec epsilon receptor II (CD23b) genes activated
      via binding of an interleukin-4-induced transcription factor to a novel
      responsive element.
AB  - Interleukin-4 (IL-4) has important regulatory functions in the immune system,
      particularly in the generation of immunoglobulin E, the principal mediator of
      allergic responses. The molecular basis of IL-4 action has remained elusive so
      far. Here we report on a novel human transcription factor, termed nuclear factor
      IL-4 (NF-IL4), which is posttranslationally activated by IL-4 in lymphoid and
      monocytic cells. Homologous binding sequences for NF-IL4 were identified in the
      promoter regions of the IL-4 controlled CD23b and I epsilon genes. We defined a
      palindromic 9-bp consensus sequence (5'-TYCYRRGAA-3') as IL-4-responsive element
      (IL-4RE). Point mutation analysis of the CD23b promoter showed that binding of NF
      IL4 to the IL-4RE is essential for the initiation of gene transcription in
      response to IL-4. NF-IL4 was not activated by Ca2+ ionophore, phorbol ester and
      cAMP either alone or in combination suggesting a non classical pathway for IL-4
      signal transduction.

PMID- 8258320
TI  - Cyclosporin A inhibits T cell receptor-induced interleukin-2 synthesis of human T
      lymphocytes by selectively preventing a transmembrane signal transduction pathway
      leading to sustained activation of a protein kinase C isoenzyme, protein kinase C
      beta.
AB  - Stimulation of human peripheral blood lymphocytes via T cell receptor/CD3 complex
      resulted in a bimodal activation of protein kinase(s) C (PKC). Within 10 min of
      stimulation PKC-alpha was translocated to, and thus activated in, the plasma
      membranes of human lymphocytes, followed by a fast dissociation of this isotype
      from the plasma membrane. This short term activation and translocation PKC-alpha
      proved to be cyclosporin A (CsA) insensitive. After 90 min of stimulation PKC
      beta was translocated to and remained bound to the plasma membranes for up to 4
      h. Preincubation of human lymphocytes with 200 ng/ml CsA specifically and
      completely abolished the sustained activation of PKC-beta. Neither the phorbol
      ester-induced direct activation of PKC nor the specific activity of the plasma
      membrane-bound enzyme was influenced by CsA, suggesting that a signal
      transduction pathway leading to sustained activation of PKC-beta was influenced
      by the immunosuppressive agent. In fact, CsA inhibited, in a concentration
      dependent manner, the activation of lysophosphatid acyltransferase-catalyzed
      elevated incorporation of cis-polyunsaturated fatty acids into plasma membrane
      phospholipids. While interleukin-2 (IL-2) synthesis and cellular proliferation
      were completely inhibited by 200 ng/ml CsA in BMA 030- or BMA 031-stimulated
      cells, expression of high-affinity IL-2 receptors was not influenced by the
      immunosuppressive drug. These results suggest that synthesis and expression of
      high-affinity IL-2 receptors might be regulated by a signal-transducing pathway
      involving activation and translocation of PKC-alpha. Lysophosphatid
      acyltransferase-catalyzed incorporation of cis-polyunsaturated fatty acids might
      represent another mechanism of signal transduction implicated in the activation
      and translocation of PKC-beta, which is specifically inhibited by CsA.
      Neutralization of PKC-beta by introducing anti-PKC-beta antibodies prevented IL-2
      synthesis and proliferation in stimulated human lymphocytes. The results suggest
      a possible link between activation of PKC-beta and regulation of IL-2 synthesis
      in activated human lymphocytes. Thus, inhibition of the activation and
      translocation of PKC-beta by CsA may result in inhibition of IL-2 gene expression
      in human lymphocytes.

PMID- 8258321
TI  - Differential effect of transporter Tap 2 gene introduction into RMA-S cells on
      viral antigen processing.
AB  - The protein products of the Tap (Transporter associated with antigen processing)
      1 and 2 genes are presumed to deliver peptides across the endoplasmic reticulum
      (ER) for assembly with major histocompatibility complex (MHC) class I molecules.
      The antigen processing-defective cell line RMA-S (H-2b) has a premature stop in
      the Tap 2 gene and probably therefore fails to deliver peptides into the ER,
      which leads to a low level of cell surface MHC class I molecules. Transfection of
      a Tap 2 gene restores to RMA-S both MHC class I molecule expression and the
      ability to present influenza viral antigens. We investigated the ability of RMA-S
      cells transfected with a Tap 2 gene to process and present alloantigens, Sendai
      and Rauscher viral antigens to allogeneic and virus-specific cytotoxic T
      lymphocytes. We found that allogeneic peptides as well as Rauscher and Sendai
      viral peptides can be processed and presented by RMA-S but at reduced levels.
      Transfection of a Tap 2 gene of mouse (BALB/c, H-2d) or rat origin into RMA-S
      increased the presentation of Sendai viral antigens and partially restored the
      presentation of allogeneic antigens. The already low level of Rauscher viral
      peptides presented by RMA-S is not elevated by transfection of either Tap 2 gene
      into RMA-S. This indicates a differential effect of transfection of a Tap 2 gene
      of rat or allogeneic mouse origin into RMA-S on viral antigen processing.

PMID- 8258322
TI  - TH2 activated cells prevent experimental autoimmune uveoretinitis, a TH1
      dependent autoimmune disease.
AB  - Mercuric chloride (HgCl2) injections protect (Lewis x Brown-Norway) F1 (F1) rats
      against experimental autoimmune uveoretinitis (EAU) induced by immunization with
      the retinal S antigen (S-Ag); in contrast HgCl2-injected F1 rats develop EAU
      following transfer of lymph node (LN) cells from rats immunized with S-Ag alone.
      In the present study we demonstrate that the ability of LN cells from rats
      protected against EAU to transfer the disease into naive F1 rats was considerably
      reduced. These LN cells neither produced interleukin (IL)-2 nor (interferon (IFN)
      gamma but exhibited mRNA for IL-4. In contrast, LN cells from diseased rats
      easily transferred EAU into naive F1 rats, produced significant IL-2 and IFN
      gamma levels but barely exhibited mRNA for IL-4. Furthermore protected rats
      predominantly produced IgG1 anti-S-Ag antibodies, while diseased rats produced
      IgG2b anti-S-Ag antibodies and the increase in expression of MHC class II
      molecules on B cells was higher in protected rats than in diseased rats. These
      data suggest that (1) to exert a protective effect, HgCl2 must act at an early
      stage of differentiation of precursors of S-Ag specific T cells, and (2) this
      effect is related to the preferential activation of TH2 cells to the detriment of
      uveitogenic TH1 cells. Finally, these results indicate that activation of TH2
      cells protect from a TH1-dependent autoimmune disease.

PMID- 8258323
TI  - Continuous in vivo activation and transient hyporesponsiveness to TcR/CD3
      triggering of human gut lamina propria lymphocytes.
AB  - Three-color immunofluorescence and flow cytometric analysis showed that the vast
      majority of normal human T-lamina propria lymphocytes (LPL) expressed high levels
      of the early activation antigen CD69, together with CD45R0, irrespective of their
      CD4, CD8 or gamma/delta-TcR phenotype, indicating that they are continuously
      stimulated in vivo. Importantly, measurement of cytoplasmic [Ca2+]i showed that T
      LPL had significantly higher basal [Ca2+]i levels, compared to autologous
      peripheral blood lymphocytes (PBL). Both cytoplasmic [Ca2+]i elevation and
      inositol (1,4,5) trisphosphate generation following CD3 cross-linking by
      monoclonal antibodies in vitro were essentially abolished in T-LPL, as compared
      to autologous T-PBL. Moreover, freshly isolated LPL could be induced to
      proliferate by CD2- or CD28-mediated signals, but not by CD3-mediated signals.
      Surprisingly however, impairment in TcR/CD3-mediated early signaling and
      proliferation in T-LPL could be completely reversed by 24 h incubation of the
      cells at 37 degrees C in culture medium, a condition which allowed basal
      intracellular [Ca2+]i to return to levels comparable to peripheral T cells. Our
      data suggest that selective hyporesponsiveness to TcR/CD3-mediated signaling may
      represent a transient event during continuous in vivo activation of mucosal
      lymphocytes.

PMID- 8258324
TI  - The Bruton's tyrosine kinase gene is expressed throughout B cell differentiation,
      from early precursor B cell stages preceding immunoglobulin gene rearrangement up
      to mature B cell stages.
AB  - X-linked agammaglobulinemia (XLA) is an immunodeficiency disease in man,
      resulting from an arrest in early B cell differentiation. The gene defective in
      XLA has recently been identified and encodes a cytoplasmic protein tyrosine
      kinase, named Bruton's tyrosine kinase (btk), essential for cell differentiation
      and proliferation at the transition from pre-B to later B cell stages. In this
      study we investigated btk expression by Northern blotting experiments in a series
      of human (precursor-) B cell lines, acute lymphoblastic leukemias and
      plasmacytomas. btk was found to be already expressed in very early stages of B
      cell differentiation, even prior to immunoglobulin (Ig) heavy (H) or light (L)
      chain gene rearrangements. Transcripts were also detected at the pre-B cell stage
      and in mature B cells, irrespective of the Ig H chain class expressed.
      Approximately at the transition from mature B cells to plasma cells, expression
      of the btk gene is down-regulated. In addition, the btk gene was found to be
      expressed in myeloid cell lines and acute myeloid leukemias. btk expression in
      myeloid cells is probably not a prerequisite for myeloid differentiation, since
      myeloid cells in XLA patients seem not to be affected. No btk expression was
      found in T-lineage cells. The btk expression profile, i.e. from early precursor-B
      cell stages preceding Ig rearrangement up to mature B cells, supports the
      hypothesis that the XLA defect resides in a critical step of B cell development
      which is independent of the Ig gene recombination machinery.

PMID- 8258325
TI  - Increased number of cytotoxic T cells within CD4+8- T cells in beta 2
      microglobulin, major histocompatibility complex class I-deficient mice.
AB  - Targeted disruption of beta 2-microglobulin gene results in deficient major
      histocompatibility complex class I expression and failure to develop CD4-8+ T
      cells. Despite this, beta 2 M-/- mice reject skin grafts and cope with most viral
      infections tested. We asked whether CD4+8- cytotoxic T cells would play a role in
      compensating for the defect in CD4-8+ cytotoxic T cell function. We found that
      the cytotoxic activity against class II+ targets is significantly higher among
      CD4+8- T cells of beta 2M-/- than among those of beta 2M+/+ mice. In the limiting
      dilution experiment, we showed that the precursor frequency for the cytotoxic,
      CD4+8-, class II-specific T cells is at least fivefold higher in beta 2M-/- than
      in beta 2M+/+ mice. These results suggest that CD4+8- cytotoxic T cells could
      play a major role in carrying out cytotoxic function in beta 2M-/- mice.

PMID- 8258326
TI  - Antigen-independent adhesion of CD4 CD45RA T cells from cord blood.
AB  - Antigen-independent adhesion of resting adult CD4+ CD45RO+ T cells to B
      lymphocytes has been shown to be transient and can be down-regulated by CD4 major
      histocompatibility complex (MHC) class II molecule interactions. Conversely,
      adhesion of adult CD4+ CD45RA+ subpopulation to B cells is not regulated by
      ligands of CD4. We have investigated the regulation of adhesion of cord blood
      CD45RA+ CD4+ T lymphocytes. In contrast to adult CD45RA+ CD4+ T cells, cord blood
      CD45RA+ CD4+ T cells were strongly sensitive to the down-regulation of adhesion
      mediated by the CD4-HLA class II interaction, since adhesion to MHC class II(+) B
      cells was transient and inhibited by an anti-CD4 antibody. In addition, human
      immunodeficiency virus gp160, synthetic gp106-derived peptides encompassing a CD4
      binding site inhibited conjugate formation between cord blood CD45RA+ CD4+ T
      cells and B cells. Following activation of the cord blood CD4 T cells by an anti
      CD3 antibody, a conversion from a transient to a stable adhesion pattern of cord
      blood CD4 T cells to B cells occurred in 2 days. The reversal to a transient
      adhesion occurred at day 8 following anti-CD3 activation in correlation with a
      complete shift to a CD45RO phenotype of the cord blood CD4 T cells. These data
      suggest that CD4 T cell adhesion can be developmentally regulated.

PMID- 8258327
TI  - Interleukin-5 expressed by a recombinant virus vector enhances specific mucosal
      IgA responses in vivo.
AB  - Several in vitro studies have shown that murine interleukin-5 (mIL-5) enhances
      IgA production by activated mucosal B cells. To date, however, there is no
      evidence that this factor significantly up-regulates mucosal IgA responses in
      vivo. Here, we show that expression of the gene for mIL-5 in a recombinant
      vaccinia virus vector markedly increases IgA responses to co-expressed
      heterologous antigen in the lungs of mice given intranasal inocula of the virus.
      The elevated local IgA responses to vectors expressing mIL-5 peaked at a fourfold
      higher level than those elicited by control virus at 14 days after infection and
      were sustained for at least 4 weeks. Increased IgA responses were abrogated in
      mice treated with monoclonal antibody against mIL-5 and were not detected in
      systemic lymphoid tissue. No enhancement of specific IgG levels was found either
      locally or systemically. Our results indicate that mIL-5 selectively enhances the
      development of mucosal IgA responses in vivo and suggest that expression of this
      factor in mucosal vaccine vectors may stimulate local immune reactivity.

PMID- 8258328
TI  - The mitogenic response of T cells to interleukin-2 requires Raf-1.
AB  - The product of the c-raf-1 proto-oncogene, Raf-1, is known to encode a 74-kDa
      ubiquitously expressed cytoplasmic serine/threonine kinase. Various growth
      factors such as epidermal growth factor, acidic fibroblast growth factor,
      platelet-derived growth factor, insulin, granulocyte-macrophage colony
      stimulating factor, interleukin (IL)-2, IL-3 and erythropoietin have been shown
      to induce phosphorylation of Raf-1, thereby activating Raf-1 kinase. Raf-1 is,
      thus, believed to play a role in coupling growth factor receptors to
      proliferation. We have examined the role of Raf-1 in the mitogenic response of
      human peripheral blood-derived IL-2 receptor expressing T cells to human
      recombinant IL-2 employing c-raf antisense (AS) oligodeoxyribonucleotide. Uptake
      studies of oligonucleotides indicated that incorporation of oligomers was maximal
      at 4 h and oligodeoxynucleotides remained stable in these cells for up to 24 h.
      Treatment of T cells with the AS oligodeoxyribonucleotide in intracellular duplex
      formation followed by efficient translation blockade of c-raf-1. In contrast,
      sense (S) and nonsense (NS) oligodeoxynucleotides failed to form intracellular
      duplexes and did not interfere with translation of c-raf-1, suggesting specific
      elimination of c-raf-1 by the AS oligomer. Proliferation of T cells
      ([3H]thymidine incorporation) following exposure to IL-2 was substantially
      reduced when the c-raf-1 AS oligodeoxyribonucleotide was added to cultures, while
      the mitogenic response to this factor remained almost unaffected in the presence
      of S and NS oligodeoxyribonucleotides.

PMID- 8258329
TI  - Development of T cells in SCID mice grafted with fetal thymus from AKR mice or
      F344 rats.
AB  - To examine the development of T cells within an allogeneic or xenogeneic
      environment, we engrafted the fetal thymus from AKR mice or F344 rats under the
      kidney capsule of SCID mice (mTG and rTG mice). T lymphopoiesis developed in SCID
      mice 2 months after transplantation, although the ratio of CD4/CD8 in both
      experimental groups was different from that of normal control. T cells in mTG
      mice did not show in vitro proliferation or cytotoxicity against either host-type
      C.B-17 (H-2d) or donor-type AKR (H-2k) cells, while they exerted potent
      activities against third-party B10 (H-2b) cells. In contrast, T cells in rTG mice
      exhibited proliferation against both host-type C.B-17 and donor-type F344 rat
      cells. Consistently, graft-vs.-host disease symptoms developed in these mice and
      histological examination showed impressive infiltration of lymphocytes into the
      skin or into the mucosal layers of the stomach. Activated state of T cells in rTG
      mice was also evidence by the positive expression of interleukin-2 receptor.
      Taken together, fetal thymus appears to contain progenitor cells which are
      sufficient for in vivo reconstitution of T lymphopoiesis, but species-specific
      environment is important for the induction of tolerance. In mTG mice, V beta 6+ T
      cells reactive to donor Mlsa determinants and V beta 3+ T cells reactive to host
      Mlsc determinants were deleted, suggesting that tolerance was regulated mainly by
      clonal deletion. By contrast, V beta 11+ T cells reactive to Mlsf determinants
      were not deleted possibly due to the lack of their ligands.

PMID- 8258330
TI  - The invariant chain induces compact forms of class II molecules localized in late
      endosomal compartments.
AB  - The invariant chain (Ii) binds to newly synthesized major histocompatibility
      complex (MHC) class II molecules and is targeted to an acidic compartment where
      it is degraded. To evaluate its role on the conformation and the subcellular
      distribution of murine MHC class II molecules we have established stable L cell
      transfectants expressing class II IAk heterodimers alone or in conjunction with
      p31 and p41 Ii chains. In these cells, class II molecules were present under
      three forms: alpha beta heterodimers bearing high mannose carbohydrate moieties,
      and fully glycosylated alpha beta heterodimers that are sensitive or resistant to
      sodium dodecyl sulfate dissociation at 20 degrees C. The latter class II
      molecules called compact heterodimers, were here highly induced in Ii-positive
      cells. Using in situ iodination of endosomal compartments, class II heterodimers
      were detected in late endosomal compartments essentially as compact forms in Ii
      positive cells, and as non-compact forms in Ii-negative cells. Using confocal
      microscopy, IAk molecules were located in compartments distinct from early
      endosomes labeled with transferrin, but partially coincident with vesicles
      containing fluid-phase markers, and highly coincident with compartments
      containing large amounts of cathepsins B, D, H, and L in Ii-positive and Ii
      negative cells. At the ultrastructural level, class II molecules were mostly
      present in multivesicular bodies, even without Ii expression. But Ii chains were
      needed to induce an efficient presentation of the hen egg lysozyme antigen and
      were sufficient to promote a major conformational change of the late endosomal,
      and/or lysosomal resident, class II molecules. Ii molecules are presumably
      playing a chaperoning function favoring the association of peptides with class II
      molecules in endosomal compartments.

PMID- 8258331
TI  - Major histocompatibility complex class II-restricted presentation of secreted and
      endoplasmic reticulum resident antigens requires the invariant chains and is
      sensitive to lysosomotropic agents.
AB  - We have tested the involvement of the invariant chains (Ii) p31 and p41 in the
      presentation of peptides derived from hen egg lysozyme (HEL) constructs targeted
      to different intracellular compartments within transfected fibroblasts. The
      endogenous HEL constructs were either present in the cytosol (HELc), secreted
      (HELs), or linked to the mammalian (KDEL C-terminal sequence that causes
      retention of HEL in the endoplasmic reticulum (ER)/pre-Golgi recycling
      compartment (HELr). Using Ii-negative antigen-presenting cells, the presentation
      of HELr to a HEL 46-61 specific T cell hybridoma was far less efficient than the
      presentation of the HELs. High levels of Ii expression enhanced drastically the
      presentation of the HEL 46-61 determinant derived from both HELr and HELs. HELr
      and HELs presentation was fully sensitive to lysosomotropic agents such as
      chloroquine, indicating that the formation of complexes between major
      histocompatibility complex (MHC) class II molecules and determinants derived from
      endogenous antigens entering the secretory pathway is taking place in an acidic
      compartment. The degradation and dissociation of Ii might be a prerequisite for
      the efficient presentation of endogenously derived determinants by MHC class II
      molecules, as for the presentation of most exogenous antigens. All our results
      are compatible with the notion that endogenous molecules being translocated into
      the lumen of the ER could be presented by class II molecules through a processing
      pathway involving an acidic compartment in which Ii chains dissociate from class
      II molecules.

PMID- 8258332
TI  - Generation of a novel CD8+ cytotoxic T lymphocyte that requires soluble factor to
      lyse autologous antigen-presenting cells.
AB  - We reported the existence of high and low responders to the streptococcal cell
      wall antigen (SCW) in the human population. To analyze the mechanism of the low
      responsiveness to SCW at the cellular level, we established SCW-specific CD4+ T
      cell lines. During the course of generation of a SCW-specific CD4+ T cell line
      restricted by HLA-DQ from a low responder, we obtained autoreactive CD8+
      cytotoxic T lymphocytes as a cell line (HYCD8). They proliferated in the presence
      of autologous monocytes and IL-2, without SCW. HYCD8 lysed autologous monocytes
      and Epstein-Barr virus-transformed B lymphoblastoid cell line (BLCL). This
      cytotoxic activity was specifically inhibited by an anti-HLA class I framework
      monoclonal antibody and restricted by HLA-B52 or B54 specificity, as judged by
      killing activity against panel cells and HLA class I-transfected BLCL. It was
      unique to HYCD8 that the HLA class I-restricted cytotoxicity was observed only in
      the presence of soluble factor with low molecular mass (< 10(4) Da) produced
      mainly by B cells, which could not be replaced by known cytokines and their
      mixtures. We thus describe novel HLA class I-restricted cytotoxic CD8+ T cells
      that kill antigen-presenting cells in a soluble factor-dependent manner.

PMID- 8258333
TI  - Selection of internalization-deficient cells by interleukin-2-Pseudomonas
      exotoxin chimeric protein: the cytoplasmic domain of the interleukin-2 receptor
      beta chain does not contribute to internalization of interleukin-2.
AB  - To study the structural basis of ligand-induced receptor-mediated internalization
      of interleukin-2 (IL-2), a strategy has been developed to generate variant T
      cells that are deficient in internalization of this cytokine. IL-2 receptor (IL
      2R) alpha- and beta-bearing EL4 cells, that express high-affinity IL-2R and
      internalize IL-2, were treated with low doses of IL-2-Pseudomonas exotoxin
      chimeric protein (IL-2-PE40). This treatment resulted in isolation of a variant
      (CX1) that was unable to express high-affinity IL-2R or internalize IL-2.
      Transfection of CX1 with the IL-2R beta cDNA led to surface expression of IL-2R
      beta and high-affinity IL-2R as well as the ability to internalize IL-2. This
      finding indicates that the absence of the beta subunit was the sole defect in CX1
      responsible for its failure to internalize IL-2. By transfecting CX1 with mutated
      beta cDNA, several CX1 transfectants were produced that expressed a beta-subunit
      that lacked all amino acids of the intracytoplasmic region. These transfectants
      expressed high-affinity IL-2R and internalized IL-2 at a rate comparable to cells
      expressing wild-type beta-chain. These results demonstrate that internalization
      of IL-2 is independent of any signals contained in the intracytoplasmic tail of
      the beta subunit and raise the possibility that such signals may be entirely
      contained within the gamma subunit.

PMID- 8258334
TI  - HLA class II molecule-mediated signal transduction mechanism responsible for the
      expression of interleukin-1 beta and tumor necrosis factor-alpha genes induced by
      a staphylococcal superantigen.
AB  - Superantigens including staphylococcal enterotoxins (SE) bind to major
      histocompatibility complex class II molecules and interact with T cells bearing
      particular V beta chains. SEB was shown to induce the expression of interleukin
      (IL)-1 beta and tumor necrosis factor (TNF)-alpha genes in human peripheral blood
      monocytes bearing HLA class II molecules. Monoclonal antibodies directed against
      HLA-DR and -DQ abolished the SEB-induced expression of both the IL-1 beta and TNF
      alpha genes, suggesting that the HLA class II molecules mediated the gene
      expression. Therefore, we investigated the signal transduction mechanism
      responsible for the expression of IL-1 beta and TNF-alpha genes induced by
      binding of SEB to the HLA class II molecules. Three protein tyrosine kinase (PTK)
      inhibitors, genistein, herbimycin A, and tyrphostin, each of which has a
      different mechanism of action, strongly inhibited the expression of the monokine
      mRNA induced by SEB. Analyses of PTK activity revealed that SEB induced a rapid
      increase of membrane-associated PTK activity and this was blocked by tyrphostin.
      Furthermore, H-7 inhibited the expression of the monokine mRNA induced by SEB,
      suggesting the involvement of protein kinase C (PKC) in the signaling pathway.
      The involvement of PKC was confirmed by the observations that phorbol 12
      myristate 13-acetate (PMA), a direct activator of PKC, induced the expression of
      the monokine mRNA and that SEB evoked the activation of membrane-associated PKC.
      Both activation of PKC and expression of the monokine mRNA induced by SEB
      appeared to be inhibited by tyrphostin, but those induced by PMA were not. Taken
      together, these findings indicate that both PTK and PKC play essential roles in
      HLA class II molecule-mediated signal transduction elicited by SEB and that PTK
      activation may precede PKC activation in the signaling pathway.

PMID- 8258335
TI  - Half-life of antigen/major histocompatibility complex class II complexes in vivo:
      intra- and interorgan variations.
AB  - We have determined the half-life in vivo of antigen/MHC class II complexes in
      different organ microenvironments. Mice were "pulsed" with myoglobin
      intravenously and MHC class II-positive antigen-presenting cell (APC) populations
      from different organs were isolated after various time intervals. Specific
      antigen/MHC complexes were quantitated by co-cultivation of the APC subsets with
      myoglobin-specific T-T hybridoma cells in vitro. Half-lives of antigen/MHC
      complexes differed both between organs and between compartments of the same
      organ. Half-lives in peripheral organs (spleen and bone marrow) ranged between 3
      and 8 h, whereas in the thymus half-lives between 13 h (cortical epithelial
      cells) and 22 h (medullary dendritic cells) were observed. Half lives in vivo
      were independent of antigen processing, since intact protein or antigenic
      peptides yielded similar values. The considerably longer half-life of peptide/MHC
      complexes in the thymus as compared to peripheral organs may reflect the distinct
      role which antigen presentation plays in both organs, i.e. induction of tolerance
      versus induction of immunity.

PMID- 8258336
TI  - Carrier-mediated uptake and presentation of a major histocompatibility complex
      class I-restricted peptide.
AB  - Antigenic peptides derived from endogenous or viral proteins can associate with
      class I or class II major histocompatibility complex (MHC) molecules, while
      exogenous antigens are endocytosed, processed intracellularly and presented on
      MHC class II molecules. Here we describe a method that allows the presentation of
      an MHC class I-restricted antigenic peptide on MHC class I molecules, although it
      was taken up from the outside. The HLA-A2-restricted influenza virus matrix
      protein-derived peptide (flu, 57-68) was used either in soluble form or coupled
      via an S-S bridge to transferrin (Tf-flu). Target cells were incubated with flu
      or Tf-flu and the effective antigen presentation was detected in a cytotoxicity
      assay using flu peptide-specific, HLA-A2-restricted CD8+ cytotoxic T lymphocytes.
      Sensitization of target cells with Tf-flu required 5 to 10 times higher molar
      concentrations of peptide compared to sensitization with soluble free peptide.
      The Tf-flu construct was taken up by the cells via the Tf receptor (CD71) as the
      binding of Tf-flu was blocked by an excess of Tf. In contrast to the flu peptide,
      cytotoxicity elicited by Tf-flu was blocked by brefeldin A but not by chloroquine
      nor inhibitors of intracellular reducing steps, like 1-buthionine-(s,r)
      sulfoximine or n-ethylmaleimide. Presentation of the flu peptide derived from Tf
      flu construct is not hindered in the mutant T2 cell line, which lacks genes
      coding for transporter proteins for antigenic peptides (TAP1/TAP2) and
      proteasomes subunits, suggesting that the processing pathway described in this
      report may involve TAP-independent steps.

PMID- 8258337
TI  - Major histocompatibility complex class I-binding peptides are recycled to the
      cell surface after internalization.
AB  - Cytotoxic T lymphocytes (CTL) recognize target antigens as short, processed
      peptides bound to major histocompatibility complex class I (MHC-I) heavy and
      light chains (beta 2-microglobulin; beta 2-m). The heavy chain, which comprise
      the actual peptide binding alpha-1 and alpha-2 domains, can exist at the cell
      surface in different forms, either free, bound to beta 2-m or as a ternary
      complex with beta 2-m and peptides. MHC-I chains are also known to internalize,
      and recycle to the cell surface, and this has been suggested to be important in
      peptide presentation. Whether MHC-I-bound peptides also can recycle is not known.
      We have investigated this by using both peptide transporter mutant RMA-S cells
      and EL4 cells loaded with Db-binding peptides, by two different approaches.
      First, peptides were covalently linked with galabiose (Gal alpha 4Gal) at a
      position which did not interfere with Db binding or immunogenicity, and peptide
      recycling tested with Gal2-specific monoclonal antibodies. By flow cytometry, a
      return of Gal2 epitopes to the cell surface was found, after cellular
      internalization and cell surface clearance by pronase treatment. This peptide
      recycling could be discriminated from free fluid-phase uptake and was inhibited
      by methylamine, chloroquine and low temperature (18 degrees C) but not by
      leupeptin. Second, specific CTL were reacted with peptide-loaded target cells
      after complete removal of surface Db molecules by pronase, and after different
      times of incubation at 37 degrees C to allow reexpression. By this procedure,
      reappearance of target cell susceptibility was confirmed. The results are in
      agreement with a model for optimizing peptide presentation by recycling through
      an intracellular compartment similar to early endosomes in certain antigen
      presenting cells.

PMID- 8258338
TI  - IgE-binding molecules (Mac-2/epsilon BP) expressed by human eosinophils.
      Implication in IgE-dependent eosinophil cytotoxicity.
AB  - Macrophage cell-surface protein 2 (Mac-2), a galactose specific S-type lectin
      identified in inflammatory macrophages, presents a high degree of homology with
      the rat IgE-binding protein (epsilon BP). In the present study, we show by
      different experimental approaches that human eosinophils can express Mac
      2/epsilon BP. Flow cytometry analysis revealed that a large proportion of
      eosinophilic patients expressing binding sites for IgE on their eosinophil
      membrane, were able to bind anti-Mac-2 monoclonal antibody (mAb). Northern blot
      performed with eosinophil RNA hybridized with the human Mac-2 or epsilon BP cDNA
      probes revealed that eosinophils presented a unique transcript at 1.2 kb.
      Immunoprecipitation of eosinophil extracts with anti-Mac-2 mAb revealed the
      presence of a molecule of 29 kDa corresponding to Mac-2 protein, as well as one
      additional molecule of 15 kDa, absent from control alveolar macrophages. The
      function of these molecules was investigated in a radiolabeled IgE binding assay.
      Anti-Mac-2 mAb as well as galactose and lactose saccharides significantly
      inhibited the binding of radiolabeled human myeloma IgE protein to eosinophils.
      Moreover, the dose-dependent inhibition by anti-Mac-2 mAb of IgE-dependent
      eosinophil-mediated cytotoxicity towards parasite targets indicated the role of
      these IgE-binding molecules in the function of human eosinophils. These results
      suggest that in addition to transmembrane receptors, lectin-type molecules can
      participate in the IgE-dependent effector function of eosinophils.

PMID- 8258339
TI  - Enhancement of disease by neutralizing antiviral antibodies in the absence of
      primed antiviral cytotoxic T cells.
AB  - The effects of neutralizing antibodies on the disease course in mice infected
      with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were evaluated.
      Whereas non-neutralizing antisera exhibiting high enzyme-linked immunosorbent
      assay titers had no effect on T cell responses and their consequences,
      neutralizing antisera modulated them variably. Neutralizing antibodies were able
      to prevent lethal choriomeningitis after intracerebral infection with a
      neurotropic LCMV-isolate (ARMSTRONG) although they could not control local virus
      replication. The same antibodies exhibited little or no protective effect on
      choriomeningitis induced by LCMV-WE, a viscerotrope isolate. Surprisingly, these
      antibodies rendered mice much more susceptible to choriomeningitis after
      intracerebral infection with LCMV DOCILE, a very rapidly spreading lymphocyto
      viscerotrope virus; in this situation antibodies prevented overwhelming infection
      which causes deletion of immunopathogenic cytotoxic T cell responses. Thus
      preexisting neutralizing antiviral antibodies had little influence on local virus
      spread in peripheral tissues but they reduced hematogenic spread and infection of
      antigen-presenting cells; thereby they influenced the primary cytotoxic T cell
      (CTL) response and indirectly modulated the extent of T cell-mediated
      immunopathology in peripheral organs. These results may explain why vaccines
      inducing neutralizing antibodies but no CTL may enhance an immunopathological
      disease caused by challenge infection with a noncytopathic virus.

PMID- 8258340
TI  - Beta 2-adrenergic stimulation causes detachment of natural killer cells from
      cultured endothelium.
AB  - Physical exercise, mental stress, or infusion of beta-adrenergic agonists result
      in an increase in the number of natural killer (NK) cells in the peripheral
      circulation. In view of the specific migration pattern of NK cells in vivo, it
      has been suggested that these cells may be released from the marginating pool in
      blood vessels. In the present report, the in vitro effect of catecholamines on
      the adhesion of NK cells to unstimulated human endothelial cells (EC) was
      characterized. Peripheral blood mononuclear cells were allowed to adhere to
      monolayers of EC, after which the adherent lymphocyte fraction was analyzed
      phenotypically by flow cytometry. NK cells were found to adhere preferentially to
      EC, a process that was reversed by the addition of various adrenergic agonists.
      Catecholamines selectively affected adhesion of NK cells and had no effect on T
      cell adhesion to EC, as was determined by the use of purified cell populations.
      Detachment of NK cells from EC could be achieved by short incubations (5 min)
      with epinephrine (EPI) and was concentration-dependent, with an ED50 of 2 x 10(
      10)M. Using a panel of alpha- and beta-adrenergic agonists and antagonists, we
      show that the detachment of NK cells is mediated via beta 2-adrenergic receptors.
      In line with the lower affinity for beta 2-adrenergic receptors, norepinephrine
      was less effective than EPI in inducing detachment of NK cells from EC. Direct
      activation of adenylate-cyclase with forskolin gave similar results as observed
      with EPI, indicating that signaling through cAMP is necessary to induce
      detachment of NK cells from EC. The results of the present study lend support to
      the hypothesis that catecholamines, via beta 2-adrenergic receptors, can induce
      recruitment of NK cells from the marginating pool to the circulating pool, by
      changing the adhesive interactions between NK cells and EC.

PMID- 8258341
TI  - Expressed human immunoglobulin kappa genes and their hypermutation.
AB  - The question of which germ-line V kappa genes are expressed was studied by
      sequencing 70 different cDNA clones from a human spleen library and one clone
      from a fetal liver library. The sequences were compared to a data base containing
      all germ-line V kappa gene and pseudogene sequences. In addition, 51 rearranged
      genomic V kappa genes, 170 cDNA and 74 kappa proteins from the literature were
      assigned to specific germ-line V kappa genes and included in the comparisons. Not
      all the known, potentially functional V kappa genes were found to be expressed,
      while some genes with minor defects are. The total number of expressed genes is
      smaller than expected: so far 21 germ-line genes and 5 pairs of duplicated
      identical genes are known to be transcribed. The corresponding numbers for
      rearranged genomic V kappa genes and kappa proteins are 17 plus 4 and 7 plus 7,
      respectively. A second aim of the study was to find out whether the expressed
      repertoire contains derivatives of germ-line V kappa genes still missing in our
      data base; no evidence for the existence of such genes was found. Several cDNA
      clones contained additional nucleotides between the V kappa and J kappa gene
      segments, which may be germ-line derived, inserted by terminal deoxynucleotidyl
      transferase or introduced by other mechanisms. Somatic gene conversion seems not
      to play a major role in creating the human kappa gene diversity. Various aspects
      of the hypermutation of kappa genes are discussed and the formation of block
      mutations, i.e. the alterations of two or more adjacent nucleotides is stressed
      as a remarkable feature of the process.

PMID- 8258342
TI  - Comparison of human germ-line kappa gene sequences to sequence data from the
      literature.

PMID- 8258343
TI  - Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express
      V kappa genes with no or little somatic mutation throughout life.
AB  - Peripheral blood B cells of a 67-year-old person were separated into IgM+IgD+,
      IgM+IgD-, and IgM-IgD- subsets, and nucleotide sequences of expressed
      immunoglobulin light chain variable (V) regions encoded by V kappa 3 and V kappa
      4 gene family members were determined from amplified cDNA. V region sequences
      from IgM+IgD+ cells (the major B cell population in the blood) showed no or
      little somatic mutation (0.3%), in contrast to V kappa sequences from IgM+IgD-
      and IgM-IgD- B cells (2.0% and 3.9%, respectively). This suggests that in the
      human like in the mouse, and independently of age, somatically mutated memory B
      cells accumulate in the compartment of IgM-IgD- cells, whereas the IgM+IgD+
      subpopulation consists of cells whose antibody repertoire is mainly determined by
      V region gene rearrangements and N-region insertion, at the molecular level. The
      somatically mutated IgM+IgD- cells may represent early descendants of IgM+IgD+
      cells recruited into the memory cell compartment.

PMID- 8258344
TI  - Chemical reactivity of an HLA-B27 thiol group.
AB  - Techniques have been developed to measure the reactivity of free thiols in the
      HLA class I antigen-binding cleft. HLA-B27, which sequencing predicts has a free
      cysteine at position 67, reacts rapidly with the positively charged thiol reagent
      monobromotrimethyl-ammoniobimane bromide (qBBr) to give products which are
      identifiable by isoelectric focusing. HLA-B38, B39, B64 and B65, all of which
      have a similar Cys 67, react less strongly. Several other class I molecules,
      notably HLA-C antigens, are reactive in this system, and it may be capable of
      recognizing subtypes such as A*0207 which also carry free cysteine. The
      accessibility of thiol to qBBr depends both on the chemistry of the class I
      molecule and other factors in the cell. Two human cell lines which are known to
      carry identical B27 genes but do not present the same peptides, differ
      considerably in the accessibility of their B27 thiol. Evidence from mouse cells
      transfected with mutant B27 genes suggests that a unique lysine at position 70 in
      the wild-type molecule increases reactivity to thiol-reactive metabolites. The
      failure of B27 to give a complete reaction with qBBr in our model systems
      suggests that it can exist in more than one chemical form. This may leave the
      molecule susceptible to oxidation, causing errors in T cell recognition and an
      exaggerated inflammatory response.

PMID- 8258345
TI  - Peripheral clonal deletion of antiviral memory CD8+ T cells.
AB  - Antiviral cytotoxic memory CD8+ T cells adoptively transferred to mice which are
      persistently infected with lymphocytic choriomeningitis virus WE or DOCILE
      initially proliferated extensively; they either caused the death of the recipient
      or, alternatively, disappeared within a few days. Apparently, the complete and
      coordinated induction and stimulation by widely distributed viral antigen caused
      these memory T cells to die before virus had been eliminated from the host. Thus
      memory T cells are as susceptible to peripheral exhaustion/deletion as unprimed T
      cells. These results indicate possible limitations of exclusively CD8+ T cell
      mediated adoptive immunotherapy against viral infections or tumors.

PMID- 8258346
TI  - Identification of conserved T cell receptor CDR3 residues contacting known
      exposed peptide side chains from a major histocompatibility complex class I-bound
      determinant.
AB  - We have analyzed the T cell receptor (TCR) repertoire found in the major
      histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL)
      response to the protein ovalbumin (OVA). Despite skewing towards the expression
      of V beta 5.2+TCR by OVA-specific CTL from C57BL/6 mice, we found a relatively
      high degree of diversity in V(D)J usage in both TCR alpha- and beta-chains.
      Closer examination showed that the majority of these sequences encoded negatively
      and positively charged residues at their respective TCR alpha- and beta-chain VJ
      or VDJ junctions. These junctions form the third complementarity-determining
      regions (CDR3) of the TCR polypeptides involved in the direct interaction with
      the class I-bound peptide. Crystallographic analyses of Kb-peptide complexes
      predict that the major determinant from OVA, peptide OVA257-264 (SIINFEKL),
      contains two exposed charged side chains which can contact the TCR. These are the
      negatively charged glutamic acid at determinant position 6 (P6) and the
      positively charged lysine at P7. To examine whether the TCR alpha-chain makes
      contact with P7 lysine, we established a single chain TCR transgenic C57BL/6
      mouse line where all T cells express a TCR beta-chain derived from the V beta
      5.2+ clone B3. OVA-specific T cells derived from in vivo primed transgenic mice
      preferentially expressed TCR alpha-chains that also contained negatively charged
      junctional residues despite some further variation in V alpha and J alpha
      sequences. Stimulation of naive TCR beta-chain transgenic T cells with a P7
      substitution peptide analogue induced a T cell response that was no longer cross
      reactive with the wild-type OVA257-264 determinant, suggesting that the TCR alpha
      chain from the T cell clone B3 can determine the specificity for this residue.
      Consequently, these results reveal the existence of conserved residues in the
      CDR3 of TCR alpha- and beta-chains specific for OVA257-264 and identify their
      possible orientation over the peptide-class I complex.

PMID- 8258347
TI  - VH CDR3-dependent positive selection of murine VH12-expressing B cells in the
      neonate.
AB  - Five to fifteen percent of peritoneal B1 (CD5+) cells from unmanipulated mice
      produce antibodies that bind bromelain-treated mouse red blood cells and the
      hapten phosphatidylcholine (PtC). The majority of these B cells express either of
      two VH/V kappa gene combinations, VH12/V kappa 4 or VH11/V kappa 9. Both the VH11
      and VH12 genes are rearranged to JH1 and encode third complementarity determining
      regions (CDR3) of restricted length and sequence. These and other observations
      argue strongly that PtC-specific B1 cells are antigen selected. To determine when
      selection of PtC-specific B1 cells begins in mice we have used the polymerase
      chain reaction to amplify VH12-D-JH1 rearrangements from livers of fetal and
      neonatal mice, and determined the CDR3 encoding sequences of individual clones.
      We find an unusually low ratio of productive (P) to non-productive (NP)
      rearrangements (0.4-1.0) at both developmental stages. P rearrangements in day 1
      neonates are biased in D gene use and in the sequence and length of their deduced
      VHCDR3. These biases are similar to those of PtC-specific B1 cells in the adult
      peritoneum. D gene use and CDR3 length and sequence are significantly less biased
      among VH12 P rearrangements 2 to 3 days earlier in the day 18 fetal liver. We
      suggest that this rapid change in repertoire is due to positive ligand selection
      that is dependent on the sequence of VHCDR3. We suggest further that the majority
      of VH12-expressing cells are not ligand selected and consequently undergo
      programmed cell death. The evidence of restriction in day 1 neonatal livers and
      the low P/NP ratio in the fetus suggests that selection of VH12-expressing cells
      begins before birth.

PMID- 8258348
TI  - Extensive N nucleotide addition in junctional region of T cell receptor V gamma 5
      genes rearranged in fetal liver-derived thymocytes in radiation chimera mice.
AB  - The V gamma 5 chain of T cell receptor gamma delta is preferentially expressed by
      murine fetal thymocytes. The fetal V gamma 5 gene is known to be homogeneous and
      lacks N nucleotide addition. We previously reported that V gamma 5+ cells were
      detected among donor-derived thymocytes from irradiated C3H/He mice soon after
      reconstitution with AKR/J fetal liver (FL) cells, but that only a few V gamma 5+
      were detected among donor-derived thymocytes from irradiated C3H/He mice
      reconstituted with adult bone marrow (ABM) cells. The results suggest that
      preferential use of V gamma 5 is determined at the level of T cell precursor
      generation. In the present report, we analyzed whether the junctional region of
      FL-derived V gamma 5 genes in the FL chimeras is of fetal type. Sequencing
      analysis showed that V gamma 5 genes from FL chimeras contained extensive N
      nucleotide addition and were diverse both in nucleotide sequences and deduced
      amino acid sequences. V gamma 5 genes from donor-derived thymocytes of ABM
      chimeras, which by polymerase chain reaction were revealed to be less frequent
      than those of FL chimeras, also showed extensive N addition. Furthermore, the
      terminal deoxynucleotidyl transferase (TdT) gene, which encodes an enzyme that
      adds N nucleotides into the junctional region, was expressed at high level in the
      donor-derived thymocytes of FL chimeras and normal 8-week-old AKR/J thymocytes
      but at low level in day 17 fetal AKR/J thymocytes. Our results suggest that the
      preferential rearrangement of the V gamma 5 gene is determined at the level of T
      cell precursor generation but the homogeneous V gamma 5 sequence of fetal type is
      generated only in the fetal thymic microenvironment where TdT gene expression is
      low or absent. The nomenclature of murine TcR gamma chains is according to Reilly
      et al. (Nature 1986. 321: 878). The relationship between the different
      nomenclature systems is summarized in Takagaki et al. (J. Immunol. 1989. 141:
      2112).

PMID- 8258349
TI  - Major histocompatibility complex class I molecules are required for the
      development of insulitis in non-obese diabetic mice.
AB  - An early step in the development of autoimmune diabetes is lymphocyte
      infiltration into the islets of Langerhans of the pancreas, or insulitis. The
      infiltrate contains both CD4+ and CD8+ T cells and both are required for
      progression to diabetes in non-obese diabetic (NOD) mice. It has been thought
      that the CD4+ lymphocytes are the initiators of the disease, the islet invaders,
      while CD8+ cells are the effectors, the islet destroyers. We question this
      interpretation because NOD mice lacking MHC class I molecules, hence CD8+ T
      cells, do not display even insulitis when expected.

PMID- 8258350
TI  - The lymphocyte surface antigen CD38 acts as a nicotinamide adenine dinucleotide
      glycohydrolase in human T lymphocytes.
AB  - The extracellular domain of the lymphocyte surface antigen CD38 has been recently
      shown to share a high sequence homology with a nicotinamide adenine dinucleotide
      (NAD+)-specific hydrolyzing enzyme cloned from the ovotestis of the gastropod
      Aplysia (E. States, D.J., Walseth, T.F., Lee, H. C., Trends Biochem. Sci. 1992.
      17:495). In agreement with this finding, we present here evidence that CD38
      overexpressing T cells, such as human thymocytes and cells from the human HPB-ALL
      T cell line, exhibit a NAD(+)-hydrolyzing enzymatic activity present on the outer
      surface of the cell membrane. In contrast, T lymphocytes with relatively low
      levels of CD38 marker, such as the human Jurkat cell line, display a lower
      activity. This suggests a relationship between ecto-NAD+ glycohydrolase activity
      and CD38 expression, as confirmed here when comparing wild-type Jurkat cells and
      a Jurkat cell variant overexpressing the CD38 molecule. Moreover, CD38
      immunoprecipitates from thymocytes behave as an authentic NAD+ glycohydrolase
      enzyme: it transforms NAD+ stoichiometrically into nicotinamide plus adenosine 5'
      diphosphoribose. Altogether these results strongly support the assumption that
      CD38 is actually a lymphocyte-specific NAD(+)-hydrolyzing enzyme, a finding that
      give new prospects to understand the in vivo function of this cell membrane
      protein.

PMID- 8258351
TI  - Expression of the mucosal T cell integrin alpha M290 beta 7 by a major
      subpopulation of dendritic cells in mice.
AB  - Dendritic interdigitating cells isolated from lymph nodes, Langerhans' cells from
      skin and dendritic cells from the spleen have been tested for expression of the
      mucosal T cell integrin alpha M290 beta 7. Almost all interdigitating cells
      isolated from mesenteric lymph nodes expressed the integrin at high levels; 50
      60% of those from lymph nodes draining non-mucosal sites also expressed this
      adhesion molecule. In contrast, alpha M290 beta 7 was not detected on either
      Langerhans' cells or splenic dendritic cells. Because this integrin has recently
      been shown to recognize a ligand that seems to be expressed mainly or exclusively
      by epithelial cells; it is proposed that this adhesion pathway may be important
      for antigen sampling by dendritic cells in mucosal tissues.

PMID- 8258352
TI  - Calcium ionophore-induced apoptosis of human B cells is preceded by the induced
      expression of early response genes.
AB  - We have investigated the effects of calcium ionophore on apoptosis of Ramos human
      B cells. Our results show that the calcium ionophore A23187 at defined
      concentrations leads to apoptosis of Ramos cells. The majority of cells (> 90%)
      undergo apoptosis in response to ionophore. The response is rapid and nuclear
      condensation and DNA degradation can be detected within 2 h after addition of
      ionophore. In attempts to define the changes in gene expression preceding
      apoptosis, we investigated the expression of a panel of early response genes in
      these cells after ionophore addition. We show that calcium ionophore-induced
      apoptosis of Ramos cells is preceded by the induced expression of a number of
      early response genes. These results are consistent with calcium ionophore
      initiating changes in gene expression which may be important in signaling these
      cells to undergo apoptosis.

PMID- 8258353
TI  - Lineage relationships of the fetal thymocyte subset that expresses the beta chain
      of the interleukin-2 receptor.
AB  - The beta chain (p75) of the interleukin-2 (IL-2) receptor (IL-2R) is expressed on
      up to 5-7% of fetal thymocytes on day 16 of gestation, declining thereafter to a
      minute proportion of less than 1% around birth, and of 1-2% of adult thymocytes.
      A significant part of fetal IL-2R beta+ thymocytes are gamma delta cells. The
      precursor-progeny relationships of fetal IL-2R beta+ thymocytes to the alpha beta
      T cell lineage have not been previously studied, nor has their position within
      the developmental sequence been determined. Here we show that IL-2R beta is
      expressed on a subset of very immature cells, along with high amounts of Pgp1 and
      Fc gamma RII/III, partially preceding the expression of intracellular CD3
      epsilon. IL-2-R beta disappears before expression of IL-2R alpha. IL-2R beta+
      cells, purified by sorting on day 15 of gestation, efficiently reconstituted
      fetal thymic lobes depleted of lymphoid cells by treatment with desoxyguanosine.
      They developed into T cell receptor (TCR) alpha beta+, TCR gamma delta+, and
      CD4/CD8 double- and single-positive cells in similar proportions as did sorted IL
      2R alpha+ day 15 fetal thymocytes. These data suggest that IL-2R beta expression
      marks a short period of very early thymocyte development, perhaps immediately
      after entry into the thymus.

PMID- 8258354
TI  - Requirements for high affinity binding of glycine analogs to the glycine site of
      the NMDA receptor complex.
AB  - Correlation of the isopotential contours of the optimized conformations of a
      series of alpha-amino acids, in their neutral and zwitterionic forms, with their
      potencies to inhibit [3H]glycine binding and to enhance [3H]10,11-dihydro-5
      methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding, leads to the
      following conclusions: (a) steric congestion at the amino group is detrimental to
      binding potency; (b) a zwitterionic amino acid is required for high affinity to
      the receptor; (c) a conformation in which the carboxylate group is at a 90
      degrees dihedral angle to the ammonium nitrogen is preferred for high affinity;
      and (d) placing the carbon backbone of the zwitterionic alpha-amino acid, in its
      preferred conformation, above the plane defined by the ammonium nitrogen and the
      carboxylate oxygen atoms, and viewing the molecule along the nitrogen to
      carboxylate carbon axis, there is a space forbidden to the ligand (receptor
      required-space) to the left.

PMID- 8258355
TI  - Ca2+ antagonists effect an antidepressant-like adaptation of the NMDA receptor
      complex.
AB  - Chronic, but not acute treatment of mice with nimodipine and diltiazem produce
      significant increases in the IC50 of glycine to inhibit [3H]5,7-dichlorokynurenic
      acid binding in cerebral cortex. Such adaptive changes in the ligand binding
      properties of the NMDA receptor complex are also manifested following chronic
      treatment with antidepressants from every principal therapeutic class. These
      findings indicate voltage-dependent calcium channel antagonists would be strong
      candidates for rigorous clinical trials in depressive disorders.

PMID- 8258356
TI  - Binding of serotonin and dopamine to 'serotonin binding proteins' in bovine
      frontal cortex: evidence for iron-induced oxidative mechanisms.
AB  - Binding of [3H]serotonin and of [3H]dopamine to serotonin binding proteins (SBP)
      from soluble extracts of bovine frontal cortex is increased by Fe2+ but not by
      Fe3+. It was generally believed that Fe2+ first binds to sulfhydryl groups of SBP
      and that the monoamines form coordination bonds with the trapped iron. We report
      two series of findings that are incompatible with this mechanism. First, the
      binding of both radioligands is an irreversible process since it is not
      diminished when a large excess (1 mM) of serotonin or dopamine is added to a pre
      equilibrated mixture of SBP, 0.1 mM Fe2+ and 0.2 microM radioligand. Once formed,
      binding is not impaired by chelating agents such as ethyleneglycoltetraacetic
      acid and desferal. Second, the Fe(2+)-stimulated binding is inhibited by reducing
      agents (sodium ascorbate, vitamin E, sodium metabisulfite) and by agents which
      deplete superoxide radicals (superoxide dismutase and hydrogen peroxide).
      Moreover, the effect of Fe2+ can be mimicked by oxidants (sodium periodate,
      potassium superoxide) and by the generation of superoxide radicals by the
      xanthine oxidase-catalysed oxidation of xanthine. To integrate these findings, we
      formulate the hypothesis that Fe2+ reacts with dissolved molecular oxygen to
      produce superoxide radicals, that these radicals oxidise [3H]serotonin and
      [3H]dopamine, and that the formed oxidation products bind covalently to cysteine
      residues of SBP. This alternative mechanism is also based on the ability of
      reagents which contain or modify sulfhydryl groups to decrease the binding and on
      the inability of hydroxyl radical scavengers (dimethyl sulfoxide, mannitol,
      ethanol and thiourea) to do so. Fe2+ is also able to irreversibly inactivate part
      of the binding sites on SBP (81% of the specific binding of [3H]serotonin, and
      61% for [3H]dopamine). This Fe(2+)-mediated inactivation, as well as the covalent
      nature of the binding, preclude the interpretation of saturation and competition
      binding data in terms of reversible bimolecular interactions. Yet, such
      experiments indicate that, at the same concentration, [3H]dopamine binds to 2 to
      3 times more sites than [3H]serotonin. Unlabelled dopamine acts also as a potent
      competitor at all the [3H]serotonin binding sites, whereas unlabelled serotonin
      only acts as a potent competitor at part (30%) of the [3H]dopamine binding sites.
      SBP were initially proposed to be involved in the storage, protection and/or
      transport of serotonin, and recently also of catecholamines. However, these
      potential functions of SBP can hardly be reconciled with the molecular mechanism
      of the binding. Moreover, it is conceivable that this binding actually represents
      an in vitro model for neurodegeneration.

PMID- 8258357
TI  - Natural mutation of GABAA receptor alpha 6 subunit alters benzodiazepine affinity
      but not allosteric GABA effects.
AB  - The binding of the imidazobenzodiazepine, [3H]Ro 15-4513, to cerebellar granule
      cell-specific GABAA/benzodiazepine receptors is typically insensitive to
      benzodiazepine receptor agonists such as diazepam. A mutation in the alpha 6
      subunit, causing replacement of the arginine at the 100 position by glutamine
      (Q100), has recently been found in an alcohol- and benzodiazepine-sensitive rat
      line. The mutant alpha 6(Q100)beta 2 gamma 2 recombinant receptors are sensitive
      to diazepam. The binding of [3H]Ro 15-4513 to cerebellar diazepam-insensitive
      receptors is enhanced by GABA, whereas binding to diazepam-sensitive receptors is
      inhibited. Recombinant receptors consisting of beta 2 and gamma 2 subunits
      together with the wildtype alpha 6 or mutant alpha 6(Q100) subunit showed
      positive modulation of [3H]Ro 15-4513 binding by GABA, whereas alpha 1 beta 2
      gamma 2 receptors showed negative modulation. The picrotoxin-sensitive binding of
      a convulsant, t-butylbicyclophosphoro[35S]thionate ([35S]TBPS), was inhibited in
      the alpha 6 beta 2 gamma 2 and alpha 6(Q100) beta 2 gamma 2 receptors by GABA at
      concentrations less than one-tenth of those required in the alpha 1 beta 2 gamma
      2 receptors. GABA effects on [35S]TBPS binding were only slightly affected by
      diazepam in the alpha 6(Q100) beta 2 gamma 2 receptors, while profound effects
      were seen in the alpha 1 beta 2 gamma 2 receptors in the presence of diazepam.
      The results with the mutant receptor suggest that the alpha 1 and alpha 6
      subunits are responsible for differential allosteric actions by GABA on other
      binding sites, independently of the structures defining the benzodiazepine
      binding pharmacology.

PMID- 8258358
TI  - Direct inhibition of platelet function by organic nitrates via nitric oxide
      formation.
AB  - This study investigates the mechanisms of platelet inhibition by the nitrate
      esters isosorbide dinitrate, isoidide dinitrate, isomannide dinitrate, isosorbide
      2-mononitrate and isosorbide 5-mononitrate as compared to the spontaneous nitric
      oxide (NO)-donor linsidomine, the active metabolite of molsidomine. Nitrates and
      linsidomine dose-dependently inhibited aggregation, ATP secretion and thromboxane
      formation of washed human platelets at a rank order of potency, identical with
      that for stimulation of cyclic GMP in cultured rat lung fibroblasts. While
      linsidomine (0.1 mM) caused a 3-fold platelet cGMP elevation, there was a weak (<
      or = 30%) but significant cGMP stimulation by organic nitroesters, which was
      tightly correlated with inhibition of platelet aggregation (r = 0.926, P =
      0.008). Zaprinast (2 microM) potentiated, while methylene blue (1 microM) and
      oxyhemoglobin (10 microM) reversed the antiaggregatory effects. Linsidomine (0.5
      microM-0.1 mM) dose-dependently released NO in a cell-free system. No spontaneous
      NO release was detected with organic nitroesters (0.1 mM). These data suggest
      that, to some extent, bioactivation of organic nitroesters occurs in platelets,
      resulting in platelet inhibition via the NO/cGMP system.

PMID- 8258359
TI  - Alterations of inositol phosphate turnover in striatum of aged rats.
AB  - Age-related inositol phosphate turnover in the rat central nervous system was
      investigated. Higher phospholipase-C activity and drastically higher (almost 2.5
      fold) inositol 1,4,5-trisphosphate concentration in the corpus striatum (caudate
      putamen) of extremely old (approximately 40 months) female Wistar rats in
      comparison to the young adult (approximately 3.5 months) rats were observed.
      Dopamine seems to slightly inhibit total inositol phosphate formation and this
      effect was antagonized by (-)-sulpiride.

PMID- 8258360
TI  - Characterisation of the non-5-HT3 high-affinity 'R' binding site for (R)
      zacopride in brain and other tissues.
AB  - Previous studies showed that whereas the potent 5-HT3 receptor antagonist (S)
      [3H]zacopride only labels 5-HT3 receptor binding sites, the (R)-enantiomer, (R)
      [3H]zacopride, labels these receptors and another class of high-affinity binding
      sites, named the R sites, in membranes from the rat cerebral cortex and NG 108-15
      clonal cells (Kidd et al., Eur. J. Pharmacol. 211, 133, 1992). Further studies of
      R sites revealed that they existed not only in the cerebral cortex but also in
      various other areas of the rat brain and spinal cord. In addition, R sites were
      also found in post-mortem human brain tissues. Both in the rat and in man, the
      regional distribution of central R sites was markedly different from that of 5
      HT3 receptors specifically labelled with (S)-[3H]zacopride. Under appropriate
      conditions for the specific labelling of R sites (with (R)-[3H]zacopride in the
      presence of 1.0 microM ondansetron to saturate 5-HT3 receptor binding sites--and
      0.1 mM mianserin for the determination of non-specific binding), these R sites
      were also found in rat peripheral tissues (intestine > spleen > kidney >
      testicles = liver > adrenals > lung > heart). At least in the kidney and the
      liver, the pharmacological profile of R sites corresponded exactly to that found
      in NG 108-15 cells. R sites were also detected in membranes from C6 glioma cells
      and glial cells cultured from the whole cortex of new born rats. In contrast, no
      specific binding of (R)-[3H]zacopride to R sites could be found in membranes from
      N1E-115 neuroblastoma cells. Conversely, 5-HT3 receptors could be labelled by (S)
      [3H]zacopride in the latter cells but not in C6 glioma and cultured glial cells.
      As expected from their glial location, the density of R sites increased in the
      rat hippocampus lesioned with kainic or ibotenic acid to induce local gliosis. In
      contrast, the density of hippocampal 5-HT3 receptors was unchanged in lesioned
      rats. Finally, the determination of the apparent molecular size of R sites by
      radiation inactivation gave a value (approximately 30 kDa) which was
      significantly lower than that of 5-HT3 receptor binding sites in the rat
      entorhinal cortex (40 kDa) and NG 108-15 cells (57 kDa). All these data clearly
      showed that R sites and 5-HT3 receptors are different molecular species. Whether
      R sites mediate the 5-HT3 receptor-unrelated actions of (R)-zacopride deserves
      further investigations.

PMID- 8258361
TI  - Labelling of diazepam-sensitive and -insensitive benzodiazepine receptors with
      [3H]tert-butyl-8-chloro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo [1,5
      a][1,4]benzodiazepine 3-carboxylate (ZG-63).
AB  - A diazepam-insensitive subtype of benzodiazepine receptor has been identified in
      the cerebella of several species, including man. t-Butyl-8-chloro-5,6-dihydro-5
      methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine 3-carboxylate (ZG-63) was
      recently described as a selective, high affinity ligand at diazepam-insensitive
      benzodiazepine receptors. This compound was tritiated, and its properties as a
      radioligand evaluated in rat brain membranes. Consistent with the high affinity
      and selectivity described for the non-radioactive form of this compound,
      saturation analyses of [3H]ZG-63 binding to cerebellar diazepam-insensitive and
      other, diazepam-sensitive benzodiazepine receptors revealed Kd values of 2.6 +/-
      0.2 nM and 10.6 +/- 1.4 nM, respectively. The density (Bmax) of cerebellar
      diazepam-insensitive receptors labelled with [3H]ZG-63 was not significantly
      different from values obtained with the prototypical diazepam-insensitive
      receptor ligand [3H]Ro 15-4513, representing approximately 30% of total
      cerebellar benzodiazepine receptors. [3H]ZG-63 also labelled cortical diazepam
      sensitive benzodiazepine receptors, with Bmax values that were not significantly
      different from those obtained with [3H]flunitrazepam. Diazepam-insensitive
      benzodiazepine receptors in rat cerebral cortex could be detected with [3H]ZG-63,
      but the densities of these sites are a very minor component (< or = 5%) of total
      benzodiazepine receptors. In the presence of GABA, [3H]ZG-63 behaved as a 'gamma
      aminobutyric acid (GABA) -positive', 'GABA-negative', and 'GABA-neutral' ligand
      at cortical diazepam-sensitive receptors, cerebellar diazepam-sensitive
      receptors, and cerebellar diazepam-insensitive benzodiazepine receptors,
      respectively. This profile differs from the prototype diazepam-insensitive
      receptor ligand, [3H]Ro 15-4513. Competition studies demonstrated a very high
      correlation (r2 = 0.98; P < 0.002) between the potencies of a series of
      benzodiazepine receptor ligands to inhibit [3H]ZG-63 and [3H]Ro 15-4513 binding
      to cerebellar diazepam-insensitive receptors. The high affinity and selectivity
      of [3H]ZG-63 for diazepam-insensitive receptors (diazepam-insensitive/diazepam
      sensitive ratio of approximately 0.25) together with a GABA-shift profile which
      differs from Ro 15-4513 suggests that this compound may be useful in elucidating
      the function(s) of this benzodiazepine receptor subtype.

PMID- 8258362
TI  - Desipramine desensitizes beta-adrenergic signal transduction in salivary glands:
      differential regulation with age.
AB  - We previously reported that the tricyclic antidepressant, desipramine
      desensitizes beta-adrenergic signal transduction in parotid and submandibular
      salivary glands. To determine the consequences of repeated desipramine
      administration on beta-adrenergic signal transduction in salivary glands from
      aged rats and whether the recovery after drug withdrawal is impaired, we assessed
      the effects of 28-day desipramine administration and the reversibility of this
      treatment following a 15-day washout period on beta-adrenoceptors and adenylyl
      cyclase activity in parotid and submandibular glands from F-344 rats of 6, 12 and
      24 months of age. beta-Adrenoceptors were also assessed in the cerebral cortex.
      Desipramine administration down-regulated receptor number and attenuated
      isoproterenol-stimulated adenylyl cyclase activity in all three ages of rats.
      However, the reduction in isoproterenol-stimulated adenylyl cyclase activity was
      greater than the loss of receptor number. Desipramine administration attenuated
      the efficacy of NaF-stimulated activity with no change in forskolin-stimulated
      adenylyl cyclase activity. These data suggest that in addition to desensitizing
      beta-adrenergic-mediated signal transduction, desipramine impaired G-protein
      mediated adenylyl cyclase stimulation. The recovery from desipramine
      desensitization was age dependent. beta-Adrenoceptor density recovered more
      slowly in the cerebral cortex and the submandibular gland in 24-month-old rats
      than in 6-month-old rats. In contrast, in 12-month-old rats, there was a receptor
      up-regulation and adenylyl cyclase supersensitivity. These data indicate that the
      capacity for receptor modulation is age dependent and suggest that desipramine
      treatment may down-regulate stimulatory G protein.

PMID- 8258363
TI  - Inhibition of protein tyrosine phosphatase activity in HER14 cells by melittin
      and Ca2+ ionophore A23187.
AB  - We investigated the effect of melittin and Ca2+ ionophore A23187 on protein
      tyrosine phosphatase activity in HER14 cells (NIH-3T3 cells transfected with
      human epidermal growth factor 'EGF' receptor). Cell fractions were used to
      measure protein tyrosine phosphatase activity in vitro using 32P-labeled
      poly(Glu/Tyr) (4:1) peptide as a substrate. Treatment of HER14 cells with
      melittin or with A23187, inhibited protein tyrosine phosphatase activity in the
      cell sonicate and homogenate, as well as in cytosolic and particulate fractions
      of these cells. The inhibitory effect of both drugs was prevented by
      preincubating cells with EGTA (ethyleneglycolbis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid). The cyclooxygenase inhibitor indomethacin enhanced the
      inhibitory effect of A23187, but not that of melittin. Addition of arachidonic
      acid to the cells partially prevented the inhibition of protein tyrosine
      phosphatase activity by melittin or A23187. Preexposure of cells to EGF enhanced
      the inhibitory effect of melittin--but not that of A23187. Addition of CaCl2, or
      MgCl2 to the cell homogenate inhibited protein tyrosine phosphatase activity.
      These results show that protein tyrosine phosphatase activity in HER14 cells is
      inhibited by melittin and Ca2+ ionophore A23187 through a Ca(2+)-dependent
      mechanism, and is regulated by arachidonic acid metabolism and EGF receptor
      activation.

PMID- 8258364
TI  - Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption
      in rat brain and choroid plexus.
AB  - The effect of chronic ethanol consumption (60 days) on 5-HT1C receptors as
      measured by [3H]mesulergine binding in the hippocampus, cortex, and choroid
      plexus of rats was investigated. The 5-HT1C receptor-mediated phosphoinositide
      hydrolysis in rat choroid plexus was also investigated. It was observed that
      chronic ethanol treatment significantly increased the 5-HT-stimulated
      [3H]inositol 1-phosphate ([3H]IP1) formation, as well as the density (Bmax) of 5
      HT1C receptors without causing a significant change in affinity (KD) of
      [3H]mesulergine binding in rat choroid plexus. It was also observed that chronic
      ethanol consumption had no significant effect on the Bmax or KD of 5-HT1C
      receptor binding sites in the hippocampus and cortex brain regions of rats. These
      results thus suggest that chronic ethanol consumption causes an up-regulation of
      both 5-HT1C receptors and 5-HT1C receptor-mediated phosphoinositide hydrolysis in
      rat choroid plexus but has no significant effects on the 5-HT1C receptors in
      brain. These results also suggest that 5-HT1C receptors and their functional
      response may be involved in the pathogenesis of alcohol dependence.

PMID- 8258365
TI  - Chronic ethanol exposure potentiates muscarinic receptor and alpha 2-adrenoceptor
      mediated inhibition of cAMP accumulation in PC 12 cells.
AB  - The effects of ethanol on receptor-mediated inhibition of cAMP production were
      investigated in PC 12 cells. The in vitro addition of ethanol enhanced N
      ethylcarboxyadenosine (NECA)-stimulated cAMP production without altering the
      inhibitory action of carbachol or epinephrine. A 4 day exposure of PC 12 cells to
      ethanol decreased the stimulation of cAMP production by NECA, but increased the
      inhibition of NECA-stimulated cAMP production by carbachol and epinephrine.

PMID- 8258366
TI  - Functional endothelin ETB receptors on renal papillary tubules.
AB  - Addition of endothelin-1 or endothelin-3 to rat renal papillary tubules produced
      a dose-dependent inhibition of the cAMP response to vasopressin stimulation. The
      average EC50 values were 1.1 +/- 0.6 and 2.6 +/- 1.1 nM, respectively, indicating
      mediation by an endothelin ETB receptor. Phorbol myristate acetate (1 microM)
      also inhibited the vasopressin-cAMP response and this inhibition was not additive
      with that to endothelin, indicating that the endothelin inhibition is mediated by
      activation of protein kinase C. These findings demonstrate functionally relevant
      endothelin ETB receptors on renal papillary tubules. Such receptors are a
      possible target for endothelin-3 produced within the kidney.

PMID- 8258367
TI  - Immunolocalization of DNA in preimplantation mouse embryos.
AB  - Distribution of embryonic DNA in mouse preimplantation embryos was studied by the
      immunoelectron microscopic method with colloidal gold. The embryos (one-cell,
      early or late two-cell, four-cell) were sampled separately, and immunogold
      labelling has been performed on thawed ultrathin cryosections. Condensed
      chromatin blocks were labelled very intensively. DNA labelling was predominantly
      visible over peripheral chromatin blocks and over small patches of chromatin
      localized throughout the nucleus of one-cell embryo. DNA distribution appeared to
      be more extended in the whole nucleus of early two-cell embryo. A few labelled
      chromatin clumps were observed to be associated with prenucleolar body (nucleolar
      precursor body--NPB) in this stage. Convex-shaped electron-light areas (fibrillar
      centres?) were found at the periphery of NPB in the late two-cell stage. These
      areas were labelled by scattered individual gold particles. In reticulated
      nucleolar regions (detected in four-cell embryos) immunolabelling appeared as
      individual gold particles present over the periphery of areas with loosely
      arranged material (fibrillar centres) surrounded by a denser component (dense
      fibrillar component). These consecutive changes are correlated with
      nucleologenesis and with the onset of transcriptional activity. We conclude that
      at the onset of nucleolar transcriptional activity condensed chromatin does not
      penetrate the NPB of mouse two-cell embryo.

PMID- 8258368
TI  - Kinetics of luminol-enhanced chemiluminescence induced in murine splenocytes and
      bone marrow cells by various stimulating agents.
AB  - The luminol-amplified chemiluminescence (CL) activity of murine splenocytes and
      bone marrow cells was investigated and compared. Phagocytosis was activated by
      adding starch grains, opsonized zymosan particles (OZP), or phorbol myristate
      acetate (PMA) to cell suspensions. CL was studied within a concentration range of
      3.13 x 10(6)-1.25 x 10(8) splenocytes/ml, and 1.56 x 10(6)-6.25 x 10(7) bone
      marrow cells/ml. The CL reaction intensity was increasing with rising cell
      concentration throughout the whole range studied. Starch grains and OZP elicited
      a unimodal kinetics of the CL response with a single peak after 10 min for
      splenocytes and 13-16 min for bone marrow cells. PMA activation induced a bimodal
      reaction with the first peak appearing after 3 min for either of the cell
      populations, and the second maximal peak being recorded after 6-7 min for
      splenocytes and 9-10 min for bone marrow cells.

PMID- 8258369
TI  - Rat liver nuclear receptors for thyroid hormone: binding characteristics after
      stabilization and storage.
AB  - Conditions for both stabilization and storage of rat liver nuclear receptors for
      thyroid hormone for up to 28 days were determined using agents that might protect
      the receptor from spontaneous degradation. Without any protective agent a
      statistically significant (P < 0.05) diminution of 3,5,3'-triiodothyronine (T3)
      binding occurred at 0 degree C within 14 days. Dithiothreitol can maintain the
      initial T3 maximum binding capacity (MBC) for up to 7 days at 0 degree C. The
      compounds tested, including spermine, sodium molybdate, thioglycerol, and
      nitrogen gas, had no stabilization effect on nuclear receptors. A statistically
      significant (P < 0.05) stabilization for up to 28 days at 0 degree C of the
      initial MBC of T3 receptors was observed in the presence of 0.2 mol.l-1 phosphate
      anion or 20% (w/w) glycerol. The protective effect of phosphate anion was due to
      the phosphate ion itself rather than to the high ionic strength.

PMID- 8258370
TI  - Prevention of acute graft-versus-host disease in rats using 9-(2
      phosphonomethoxyethyl) adenine (PMEA).
AB  - Severe graft-versus-host disease (GVHD) developed following intravenous
      administration of parental BN.lx lymphoid cells into (SHR x BN.lx)F1 animals.
      Clinical symptoms, including foot-pad hyperemia, slobbering, melaena, progressive
      weight loss leading to death within 3 to 4 weeks, can be completely abrogated by
      8 injections of PMEA starting 1 h after cell administration. Practically normal
      histological findings in PMEA-treated animals contrasted with nearly complete
      damage of bone marrow, lymphoid infiltration of salivary glands and even
      ulceration with hemorrhage of the epidermoid part of the stomach in untreated
      control GVHD animals.

PMID- 8258371
TI  - Antisense DNA inhibits infection of potato spindle tuber viroid.
AB  - The effect of oligodeoxyribonucleotides complementary to the region of the so
      called pathogenicity domain (nucleotides 42-78) of the upper RNA strand of potato
      spindle tuber viroid (PSTVd) (severe) on viroid infection was investigated. The
      oligonucleotides were allowed to form hybrids with PSTVd in the infection
      mixtures before inoculation. Infectivity tests were performed using intact plants
      and plant protoplasts. It was found that the DNA oligonucleotides caused
      significant reduction of viroid infection at plant and single cell levels. The
      200-fold molar excess of antisense DNA over viroid RNA is usually sufficient for
      the complete blocking of viroid infection. The inhibitory effect is strongly
      sequence specific. Inhibition by corresponding antisense RNA was much less
      efficient than that caused by antisense DNA.

PMID- 8258372
TI  - Effects of growth hormone on nitrogen balance in the hypermetabolic state: a
      selected review of the literature.

PMID- 8258373
TI  - Early emergent coronary bypass after failed angioplasty.
AB  - Emergency CABG for failed coronary angioplasty was required in 3.3 percent of
      1,625 consecutive patients undergoing angioplasties. Twenty-six percent of the
      patients died in the perioperative period. Efforts must be concentrated on
      identifying PTCA failure prior to cardiogenic shock.

PMID- 8258374
TI  - Stark II enacted as part of the Omnibus Budget Reconciliation Act of 1993.

PMID- 8258375
TI  - Thermography: a prototype of failed technology.

PMID- 8258376
TI  - Health care reform plan for Delaware.

PMID- 8258377
TI  - Central nervous system effects of the neurohypophyseal hormones and related
      peptides.
AB  - This review of the CNS effects of the neurohypophyseal hormones and related
      neuropeptides discusses recent data illustrating the significance of these
      principles in brain function, synthesis, distribution, in particular in
      extrahypothalamic brain structures, binding sites, and signal transduction.
      Binding sites for vasopressin of the vascular V1a type have been found in the CNS
      and there is evidence for the existence of a subtype of the antidiuretic V2
      receptor in the brain. Also two types of oxytocin binding sites have been
      detected. One widely distributed throughout the CNS is comparable to the uterine
      type receptor and a sexually dimorphic slightly different type is found in the
      ventromedial nucleus. Vasopressin and oxytocin can be converted to highly
      selective C-terminal fragments as AVP-(4-9) and OXT-(4-9) and shorter fragments.
      Conversely they can be acetylated. This almost completely blocks intrinsic
      activity in bioassays for central and peripheral effects. Such modifications are
      a good example of the plasticity of a neuropeptide system. For a number of CNS
      effects of the neurohypophyseal hormones, the whole molecule is required, as it
      is for their endocrine effects. This is the case for the influence of vasopressin
      on social communication, temperature regulation, epilepsy, and barrel rotation
      which may be an animal model of febrile convulsions, and some aspects of the
      central regulation of the cardiovascular system and for oxytocin on sexual
      behavior, social communication, and grooming. Nonendocrine C-terminal conversion
      products seem to exert their effects exclusively on the brain. These
      neuropeptides modulate learning and memory processes, social recognition, and
      rewarded behavior. The neuroendocrine and neuropeptide effect of vasopressin and
      oxytocin and related neuropeptides often exert their CNS effects in an opposite
      way. Neurochemical and electrophysiological studies suggest that norepinephrine,
      dopamine, serotonin, and glutamate are the neurotransmitters involved in the
      influence of the neurohypophyseal hormones and related neuropeptides on brain
      function. It appears that adequate amounts of vasopressin and oxytocin to induce
      these effects are released at the appropriate sites of action. It is postulated
      that the mix of neuropeptides released in the brain in response to environmental
      changes qualifies the behavioral, neuroendocrine, and immune response and the
      response of the autonomic nervous and vegetative systems of the organism.
      Although various other neuropeptides, such as those colocalized in
      vasopressinergic and oxytocinergic neurons, those produced in pro
      opiomelanocortin (POMC) systems, and others, play a role in the modulation of
      adaptive responses, the neurohypophyseal hormones are unique in that their
      production sites in the hypothalamus serve the periphery, the pituitary, and the
      brain.

PMID- 8258378
TI  - Feast and famine: critical role of glucocorticoids with insulin in daily energy
      flow.
AB  - The hypothesis proposed in this review is that normal diurnal rhythms in the
      hypothalamic-pituitary-adrenal (HPA) axis are highly regulated by activity in
      medial hypothalamic nuclei to effect an interaction between corticosteroids and
      insulin such that optimal metabolism results in response to changes in the fed or
      fasted state of the animal. There are marked diurnal rhythms in function of the
      HPA axis under both basal and stress conditions. The HPA axis controls
      corticosteroid output from the adrenal and, in turn, forward elements of this
      axis are inhibited by feedback from circulating plasma corticosteroid levels.
      Basal activity in the HPA axis of mammals fed ad lib peaks about 2 h before the
      peak of the diurnal feeding rhythm, and is controlled by input from the
      suprachiasmatic nuclei. The rhythm in stress responsiveness is lowest at the time
      of the basal peak and highest at the time of the basal trough in the HPA axis
      activity. There are also diurnal rhythms in corticosteroid feedback sensitivity
      of basal and stress-induced ACTH secretion which peak at the time of the basal
      trough. These rhythms are all overridden when feeding, and thus insulin
      secretion, is disrupted. Corticosteroids interact with insulin on food intake and
      body composition, and corticosteroids also increase insulin secretion.
      Corticosteroids stimulate feeding at low doses but inhibit it at high doses;
      however, it is the high levels of insulin, induced by high levels of
      corticosteroids, that may inhibit feeding. The effects of corticosteroids on
      liver, fat, and muscle cell metabolism, with emphasis on their interactions with
      insulin, are briefly reviewed. Corticosteroids both synergize with and antagonize
      the effects of insulin. The effects of stress hormones, and their interactions
      with insulin on lipid and protein metabolism, followed by some of the metabolic
      effects of injury stress, with or without nutritional support, are evaluated. In
      the presence of elevated insulin stimulated by glucocorticoids and nutrition,
      stress causes less severe catabolic effects. In the central nervous system,
      regulation of function in the HPA axis is clearly affected by the activity of
      medial hypothalamic nuclei that also alter feeding, metabolism, and obesity in
      rats. Lesions of the arcuate (ARC) and ventromedial (VMN) paraventricular (PVN)
      nuclei result in obesity and hyperactivity in the HPA axis. Moreover,
      adrenalectomy inhibits or prevents development of the lesion-induced obesity.
      There are interactions among these nuclei; one mode of communication is via
      inputs of neuropeptide Y (NPY) cells in the ARC to the VMN, dorsomedial nuclei,
      and PVN.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8258379
TI  - Risk assessment of chemical mixtures: biologic and toxicologic issues.

PMID- 8258380
TI  - Studies on the modulating effects of retinoic acid and retinol acetate using dye
      transfer and metabolic cooperation assays.
AB  - The effects of retinoic acid and retinol acetate on gap junctional communication
      were examined in two in vitro tests. Rat liver epithelial cell line IAR 203 was
      used for dye transfer assays, and hamster lung fibroblast V79 cells were used for
      metabolic cooperation assays. A reversible dose-dependent inhibition of dye
      transfer was detected after a 1-hr treatment with retinoic acid or retinol
      acetate at concentrations ranging from 10 to 50 microM. On the other hand,
      enhancement of dye transfer was observed after a 24-hr treatment with retinoic
      acid at 0.1 microM. A dose-dependent inhibition of metabolic cooperation was
      obtained with retinoic acid at noncytotoxic concentrations ranging from 5 to 50
      microM. Retinoids and TPA (1 ng/ml) acted synergistically in their inhibition of
      cell communication. Thus, the assays appear to be complementary: the dye transfer
      assay was useful in studying the time course and the reversibility of the
      inhibition or enhancement of dye transfer, whereas the metabolic cooperation
      assay was effective in quantifying the inhibitory effect of TPA or retinoids and
      interactions between them.

PMID- 8258381
TI  - Prolonged neurobehavioral and visual effects of short-term exposure to 3,3'
      iminodipropionitrile (IDPN) in rats.
AB  - Strategies for neurotoxicity testing often include initial screening tests, such
      as a functional observational battery (FOB) and motor activity assessment,
      followed by detailed characterization studies. In this study, a neurobehavioral
      screening battery (FOB and motor activity) was used to evaluate the effects of 3
      day repeated exposure to 0, 100, 200, or 400 mg/kg/day IDPN. Adult Long-Evans
      rats (males and females) were tested before dosing and 1, 14, 28, 56, and 91 days
      after the third dose. IDPN initially produced generalized CNS depression,
      weakness, and hypothermia. Thereafter, marked hyperactivity, increased
      excitability, decreased reactivity to visual and auditory stimuli, neuromuscular
      weakness, equilibrium changes, and a "waltzing syndrome" (vertical and lateral
      head movements, circling, and retropulsion) emerged and persisted for 3 months.
      Males were more severely affected than females. Following neurobehavioral
      testing, the rats were examined for visual function using flash (three
      intensities) and pattern (three pattern sizes by three contrast levels)-elicited
      visual evoked potentials (VEPs). IDPN produced changes in pattern- and flash
      elicited VEPs, thus verifying predictions made from the screening tests. However,
      the extent of the VEP changes produced by IDPN was insufficient to account for
      some of the deficits detected in the FOB, which are dependent on sensory,
      integrative, and motor functions. Thus, profound neurological effects of IDPN
      were detected using this screening battery and visual effects were confirmed
      using VEPs. These effects, following only three doses of IDPN, lasted for at
      least 3 months and thus may be permanent.

PMID- 8258382
TI  - Quantitative measurement of porphyrins in biological tissues and evaluation of
      tissue porphyrins during toxicant exposures.
AB  - Porphyrins are formed in most eukaryotic tissues as intermediates in the
      biosynthesis of heme. Assessment of changes in tissue porphyrin levels occurring
      in response to the actions of various drugs or toxicants is potentially useful in
      the evaluation of chemical exposures and effects. The present paper describes a
      rapid and sensitive method for the extraction and quantitation of porphyrins in
      biological tissues which overcomes difficulties encountered in previously
      described methods, particularly the loss of porphyrins during extraction and
      interference of porphyrin quantitation by coeluting fluorescent tissue
      constituents. In this procedure 8- through 2-carboxyl porphyrins are
      quantitatively extracted from tissue homogenates using HCl and methanol and are
      subsequently separated from potentially interfering contaminants by sequential
      methanol/phosphate elution on a C-18 preparatory column. Porphyrins are then
      separated and measured by reversed-phase high-performance liquid chromatography
      and spectrofluorometric techniques. Recovery of tissue porphyrins using this
      method is close to 100% with an intraassay variability of less than 10%. We have
      employed this procedure to measure liver and kidney porphyrin concentrations in
      male Fischer rats and to define the distinctive changes in tissue porphyrin
      patterns associated with treatment with the hepatic and renal porphyrinogenic
      chemicals, allylisopropylacetamide, and methyl mercury hydroxide, respectively.
      This method is applicable to the measurement of tissue porphyrin changes
      resulting from drug or toxicant exposures in clinical, experimental or
      environmental assessments.

PMID- 8258383
TI  - Optimization of the Hamilton-Thorn computerized sperm motility analysis system
      for use with rat spermatozoa in toxicological studies.
AB  - To optimize the Hamilton-Thorn Motility Analyzer (HTM; Hamilton-Thorn Research,
      Beverly, MA) for use in reproductive toxicology studies with rat spermatozoa, the
      accuracy and precision of the instrument were assessed under a variety of
      instrument settings. Videotapes of both fast- and slow-swimming sperm were
      analyzed repeatedly to obtain data across a range of sperm velocities as might be
      encountered as a consequence of exposure to reproductive toxicants. Acquisition
      rates were varied across the HTM menu choices (30, 19, 10, or 7 frames/sec) as
      were the number of frames analyzed (5 to 20) at each framing rate. For fast
      swimming samples (mean straight-line velocity (VSL) approximately 130
      microns/sec) generally good agreement between computer-assisted sperm analysis
      (CASA) and manually obtained data was found for percentage of motile sperm and
      straight-line velocity; i.e., CASA values were within 10% of manual values for
      most frame/rate combinations. The accuracy of these measures held true over a
      wide range of sperm concentrations and percentage motilities. However, CASA
      measures were less accurate for sperm samples of lower velocities (mean VSL
      approximately 50 microns/sec and mean VSL approximately 30 microns/sec) in that
      the velocity of very slow sperm was overestimated (particularly at 30
      frames/sec). A soft-ware change (6.5R) and performing analyses at 19 instead of
      30 frames/sec improved straight-line accuracy for the slow sperm and enhanced the
      discrimination between fast (presumably control) and slow (presumably treated)
      sperm samples. These data show that this motility analyzer could be successfully
      configured to evaluate rodent sperm samples. The use of such CASA systems in
      toxicology studies will provide valuable information that may improve human
      reproductive risk assessment.

PMID- 8258384
TI  - Effects of selected neuroactive chemicals on calcium transporting systems in rat
      cerebellum and on survival of cerebellar granule cells.
AB  - This investigation examined the relationship between alteration of Ca(2+)
      transport systems and cytotoxicity in vitro for a number of neuroactive chemicals
      including environmental pollutants. 45Ca2+ uptake as a measure of Ca2+
      sequestration was determined in mitochondria and microsomes isolated from
      cerebella of adult male Long-Evans hooded rats by differential centrifugation.
      Ca2+ extrusion, measured as Ca(2+)-ATPase activity, was determined in
      synaptosomes prepared by sucrose density gradient. Cytotoxicity (lactate
      dehydrogenase leakage) was assessed in primary cultures of cerebellar granule
      cells from 6- to 8-day-old Long-Evans rats. N-Methyl-D-aspartic acid (NMDA) did
      not alter synaptosomal Ca(2+)-ATPase activity or 45Ca2+ uptake in mitochondria
      and microsomes. However, chlorpromazine (CPZ), aluminum (Al), permethrin (PER),
      and deltamethrin (DEL) inhibited Ca2+ sequestration by mitochondria and
      microsomes. The IC50 values (microM) for CPZ, Al, PER, and DEL were 67.8, 671,
      4.2, and 91.2 for mitochondrial 45Ca2+ uptake, and 129.9, 1384, > 50, and > 200
      for microsomal 45Ca2+ uptake, respectively. CPZ, PER, and DEL also inhibited
      synaptosomal Ca(2+)-ATPase activity in a concentration-dependent manner with IC50
      values of 62.5, > 400, and 246.9 microM, indicating an effect on the Ca(2+)
      extrusion process. Al increased Ca(2+)-ATPase activity (EC50 = 833 microM).
      Although NMDA did not inhibit Ca(2+)-transport systems, it was cytotoxic at 250
      microM and higher concentrations after 2 hr of exposure. Similarly, CPZ was
      cytotoxic at concentrations of 25 and 10 microM after 4 hr exposure. However,
      PER, DEL, and Al were not cytotoxic at any concentration up to 500 microM. Of all
      the chemicals tested, CPZ was the most potent in inhibiting Ca(2+)-transporting
      systems and was also cytotoxic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258385
TI  - Styrene inhalation toxicity studies in mice. II. Sex differences in
      susceptibility of B6C3F1 mice.
AB  - Styrene is a commercially important chemical used in the production of plastics
      and resins. In initial short-term styrene inhalation studies, toxicity was
      significantly greater in male B6C3F1 mice than in females, suggesting that males
      may metabolize styrene more extensively and/or may be less able to detoxify
      reactive metabolites. In addition, a nonlinear dose-response was observed where
      toxicity and mortality were greater in mice exposed to 250 ppm than in those
      exposed to 500 ppm. These studies were conducted to investigate potential
      mechanism(s) for sex differences and the nonlinear dose-response in styrene
      toxicity by evaluating the effects of repeated styrene exposure on styrene oxide
      production, hepatic GSH availability, and hepatotoxicity in male and female
      B6C3F1 mice. Mice (36/sex/dose) were exposed to 0, 125, 250, or 500 ppm styrene 6
      hr/day for up to 3 days. Styrene exposure caused increased mortality and
      hepatotoxicity (centrilobular necrosis, increased serum liver enzymes) in males
      and females after one or two exposures to 250 and 500 ppm. Hepatic GSH levels
      were decreased in a dose-dependent manner in males and females. After one
      exposure, GSH levels in males rebounded above controls in all dose groups. After
      three exposures to 125 or 250 ppm males appeared to maintain GSH levels; GSH was
      still decreased in the 500 ppm group. GSH levels in females were decreased after
      each exposure in all dose groups to lower levels than in males, and did not
      rebound above controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258386
TI  - Styrene inhalation toxicity studies in mice. III. Strain differences in
      susceptibility.
AB  - Inhalation toxicity studies were conducted to evaluate mouse strain differences
      in the susceptibility to styrene vapors. Male and female B6C3F1, C57BL/6, Swiss,
      and DBA/2 mice (8 weeks old) were exposed to 0, 125, 250, or 500 ppm styrene 6
      hr/day, for 4 days (20/sex/dose). Histopathological changes and changes in liver
      weights were evaluated as a measure of hepatotoxicity. Styrene uptake and styrene
      7,8-oxide (SO) formation were estimated by measuring levels of styrene and SO in
      blood. An estimate of SO detoxification by conjugation with GSH was obtained by
      measuring hepatic GSH depletion. In general, mortality, increased liver weights,
      and hepatocellular necrosis were observed in the 250 and 500 ppm dose groups for
      all strains and both sexes. Considerable sex and strain differences were
      observed. Mortality, increased liver weights, and hepatocellular necrosis were
      greatest in B6C3F1 and C57BL/6 mice in the 250 ppm dose group and in males;
      hepatotoxicity was similar in both strains. Swiss mice exhibited dose-dependent
      increases in mortality, liver weights, and in hepatocellular necrosis, with only
      slight sex differences at early time points. Hepatotoxicity in DBA/2, B6C3F1, and
      C57BL/6 strains was greater at 250 than 500 ppm; however, toxicity was less
      severe in DBA/2 than in other strains based on absence of mortality in either sex
      and less extensive liver necrosis at both 250 and 500 ppm. Blood styrene and SO
      levels did not correlate well with strain differences in toxicity.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258387
TI  - Estimation of octanol-water partition coefficients and correlation with dermal
      absorption for several polyhalogenated aromatic hydrocarbons.
AB  - n-Octanol-Water partition coefficients (K(ow)) were experimentally estimated for:
      2,3,7,8-tetrachloro-and 2,3,7,8-tetrabromodibenzo-p-dioxin; 2,3,7,8-tetrachloro-,
      2,3,7,8-tetrabromo-, and 1,2,7,8-tetrabromodibenzofuran; 1,2,3,7,8-pentachloro-,
      1,2,3,7,8-pentabromo-, 2,3,4,7,8-pentachloro-, and 2,3,4,7,8
      pentabromodibenzofuran; 1,2,4,6,8,9-hexachlorodibenzofuran (HxCDF), and 3,4,3',4'
      tetrachlorobiphenyl (3,4,3',4'-TCB). The method involved correlation of
      literature K(ow) with reverse-phase high-performance liquid chromatography (RP
      HPLC) retention time for a series of 23 calibration standards and estimation of
      K(ow) for test compounds from measured RP-HPLC retention. Retention times for all
      standards and test chemicals were measured in duplicate on the same
      octadecasilane (C18) reverse-phase column with an isocratic 85:15 methanol:water
      mobile phase; solutes were detected by uv absorbance (254 nm). Literature log
      K(ow) values used for the calibration standards had been measured exclusively by
      the generator column method. Log K(ow) estimates for the test compounds in the
      present study ranged from 5.45 for 3,4,3',4'-TCB to 6.81 for HxCDF. K(ow)
      estimates were then plotted against laboratory data for the in vivo 3-day dermal
      absorption of single equimolar doses (200 pmol and 20 nmol, or approximately 1
      nmol/kg and approximately 0.1 mumol/kg) of selected test compounds in male F344
      rats. Strong inverse correlations were found between octanol-water partition
      coefficient estimates and single-dose dermal absorption for most of the compounds
      studied. In addition, RP-HPLC retention time itself appeared to be as equally
      suited as K(ow) to such correlations with dermal absorption. The structure
      activity relationships suggested in this study were sought in order to explain
      observed differences in the dermal absorption of polyhalogenated dibenzo-p
      dioxin, dibenzofuran, and biphenyl congeners differing in number, position,
      and/or type (Cl or Br) of halogen substituents. Moreover, these results should be
      of predictive value in the risk assessment of dermal exposure to polychlorinated
      dibenzo-p-dioxins, dibenzofurans, biphenyls, and their brominated analogues.

PMID- 8258388
TI  - Deposition, clearance, and shortening of Kevlar para-aramid fibrils in acute,
      subchronic, and chronic inhalation studies in rats.
AB  - The deposition and clearance of lung-deposited Kevlar para-aramid fibrils
      (subfibers) have been investigated as part of a subchronic and chronic inhalation
      toxicity testing program. Fibrils recovered from lung tissue in para-aramid
      exposed Sprague-Dawley rats were microscopically counted and measured after
      exposures to airborne fibrils which were about 12 microns median length (ML) and
      < 0.3 micron median diameter. In each of three studies lung-recovered fibrils
      were progressively shorter with increasing residence time in the lungs. Twenty
      eight days after a single 6-hr exposure at 400 respirable fibrils per cubic
      centimeter (f/cm3) the ML of recovered fibrils decreased to about 5 microns.
      Twenty-four months after a 3-week exposure to 25 or 400 f/cm3, fibrils reached
      about 2 microns ML. After 2 years of continuous exposure at 2.5, 25, or 100 f/cm3
      or 1 year exposure plus 1 year recovery at 400 f/cm3, fibril ML approached 4
      microns. In the 2-year study, the lung-fiber accumulation rate/exposure
      concentration was similar for the three highest concentrations and was about 3 x
      greater than that seen at 2.5 f/cm3, indicating that concentrations of about 25
      f/cm3 or more may overwhelm clearance mechanisms. Time required for fibrils to be
      reduced to < 5 microns in the lung was markedly less at lower exposure
      concentration and shorter exposure time. The primary shortening mechanism is
      proposed to be long fibril cutting by enzymatic attack at fibril defects.
      However, length-selective fibril deposition and clearance may contribute to
      shortening in the first few days after exposure. The enzymatic cutting hypothesis
      is supported by measured increases in numbers of short fibers following cessation
      of exposures, continued shortening of the fibril length distribution up to 2
      years following exposure, and in vitro fibril shortening after 3 months in a
      proteolytic enzyme preparation. The conclusion is that para-aramid fibrils are
      less durable in the lungs of rats than expected from the known chemical
      resistance of commercial yarn. These data suggest that at the low para-aramid
      fibril exposures found in the workplace, this fibril-shortening mechanism may
      limit the residence time of long fibers in the lungs of exposed workers. In
      addition, associated cascade impactor aerodynamic measurements indicate that due
      to their ribbon shape and curly nature, para-aramid fibrils behave
      aerodynamically larger than straight fibers.

PMID- 8258389
TI  - Neurotoxicity evaluation of N,N-diethyl-m-toluamide (DEET) in rats.
AB  - The neurotoxic potential of N,N-diethyl-m-toluamide (DEET) was evaluated
      following acute oral administration or following multigeneration plus chronic
      dietary administration to the rat. For the acute study, rats were administered
      undiluted DEET at dose levels of 50, 200, or 500 mg/kg by gavage. A dose level of
      500 mg/kg was considered to be the highest practical dose that could be evaluated
      in this study based upon observations of overt toxicity at 500 mg/kg and
      mortality at 1000 mg/kg in a dose range-finding study. The two measures of
      neurotoxicity evaluated in the acute study were functional observational battery
      (FOB) and motor activity measurements. An apparent treatment-related effect in
      thermal response time (increased) was noted for both sexes 1 hr after dosing at
      the 500 mg/kg dose level. A questionable effect on rearing activity (decreased)
      also was noted at the same dose level. For the multigeneration plus chronic
      dietary administration study, rats were administered DEET at dietary
      concentrations of 0, 500, 2000, or 5000 ppm continuously over two generations and
      then chronically for 9 months. A dietary concentration of 5000 ppm meets the
      criteria for a maximum tolerated dose (MTD) based on traditional chronic
      toxicology assessments. Evaluations included FOB, motor activity, discriminative
      acquisition and reversal in an M-maze, acoustic startle habituation, passive
      avoidance acquisition and retention, and microscopic examination of central and
      peripheral nervous tissue. The only effect that was considered to be possibly
      treatment-related was a slight increase in exploratory locomotor activity at the
      5000 ppm dose level. Based on the results of these studies, the nervous system
      does not appear to be a selective target when DEET is administered to rats either
      as a single oral dose at high dose levels or chronically at the MTD.

PMID- 8258390
TI  - In vitro cytotoxicity of mono-, di-, and trichloroacetate and its modulation by
      hepatic peroxisome proliferation.
AB  - Dichloroacetate (DCA) and trichloroacetate (TCA) are major by-products of
      drinking water chlorination. Recent experiments have shown that both of these
      compounds produce hepatic tumors in B6C3F1 mice. There was evidence that these
      effects may be associated with cytotoxic effects and/or peroxisomal
      proliferation. Therefore, in the present study the in vitro cytotoxicity of
      monochloroacetate (MCA), DCA, TCA and a metabolite, glycolate (GLY), was
      determined in hepatocyte suspensions prepared from naive and clofibric acid
      pretreated male Sprague-Dawley rats and B6C3F1 mice. Cytotoxic responses,
      measured by release of lactic dehydrogenase and/or trypan blue exclusion, were
      only observed with high concentrations (5.0 mM) of MCA and GLY in hepatocytes
      from naive animals (p = 0.025 and 0.008, respectively, Sprague-Dawley rat; p =
      0.033 and 0.001, respectively, B6C3F1 mouse). The cytotoxic responses to both
      compounds were observed much earlier and at much lower concentrations in
      hepatocytes taken from mice and rats that had been pretreated with clofibric acid
      (p < or = 0.001, Sprague-Dawley rat and B6C3F1 mouse). DCA and TCA produced no
      evidence of cytotoxicity in hepatocytes from naive or clofibric acid-pretreated
      animals of either species at concentrations up to 5.0 mM. Increasing
      concentrations of MCA and GLY resulted in dose-related depletion of intracellular
      reduced glutathione (GSH) that closely paralleled the cytotoxic responses. Only
      GLY (0.25-5.0 mM) produced increased intracellular oxidized glutathione. Neither
      DCA nor TCA was found to alter cellular GSH status in hepatocytes isolated from
      either Sprague-Dawley rats or B6C3F1 mice. It was concluded from these in vitro
      observations that DCA and TCA are not highly cytotoxic to hepatocytes. Moreover,
      the rates of their conversion to MCA or GLY may be insufficient to induce
      cytotoxic effects in hepatocytes in vivo.

PMID- 8258391
TI  - Toxicity of CI-949, a novel anti-allergy agent.
AB  - The toxicity of CI-949, an effective inhibitor of allergic mediator release in
      pharmacology models, was evaluated in rodents and dogs. Median lethal doses at 24
      hr postdose ranged from 343 to 453 mg/kg in mice and 806 to 2058 mg/kg in rats.
      Delayed toxicity was observed at 300 mg/kg and greater in mice and at 500 mg/kg
      and greater in rats. Mortality and clinical intolerance occurred in rats at 200
      and 400 mg/kg in the subacute studies, and at 100 and 150 mg/kg in the 13-week
      study. In rats, dose-dependent lymphoid tissue atrophy and depletion or necrosis
      of lymphocytes in lymphoid tissues were seen in deaths and moribund terminations.
      Although doses up to 60 mg/kg administrated for 2 weeks to dogs were well
      tolerated, 60 and 120 mg/kg in the 13-week dog study were poorly tolerated.
      Cutaneous sores, mucocutaneous purulent discharge, emesis, diarrhea, and weight
      loss were identified at these lethal doses. Histopathologic changes in dogs
      included myocardial, vascular and soft tissue inflammation, and gastric
      ulceration at 60 and 120 mg/kg, and thymic atrophy at 20 mg/kg and greater. Doses
      of 10 and 50 mg/kg were no-effect doses in 13-week repeated dose studies in dogs
      and rats, respectively. These results were used to support initial human clinical
      trials of CI-949.

PMID- 8258392
TI  - Identification of stage-specific changes in protein secretion by isolated
      seminiferous tubules from the rat following exposure to either m-dinitrobenzene
      or nitrobenzene.
AB  - The objective of this study was to identify effects of two known Sertoli cell
      toxicants on the secretion of proteins by seminiferous tubules (ST) isolated from
      adult rats at different stages of the spermatogenic cycle and cultured in vitro
      for 24 hr with [35S]methionine. Adult rats received a single oral dose of 50
      mg/kg metadinitrobenzene (m-DNB) or 300 mg/kg nitrobenzene (NB). Long lengths of
      ST at stages II-V, VI-VIII or IX-XII were then isolated from control and treated
      rats at 1 or 3 days post-treatment; selection of stages was based on the stage
      specificity of the early (24-72 hr) adverse effects of m-DNB and NB on
      spermatogenesis in vivo. In addition, ST at the same stages were isolated from
      untreated rats and cultured in the presence or absence of m-DNB or NB (10(-4)M).
      Incorporation of [35S]methionine into secreted proteins was assessed and the
      pattern of protein secretion evaluated using two-dimensional sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (2-D SDS-PAGE). ST isolated from rats
      pretreated 24 hr earlier with NB in vivo showed a significant decrease in the
      overall incorporation of [35S]methionine into secreted proteins at stages VI-VIII
      and IX-XII, whereas ST at stages II-V showed no such change; comparable protein
      changes were observed when 10(-4) M NB was added in vitro for 24 hr to ST
      isolated at the same stages from untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258393
TI  - Cataractogenic effects in rats following chronic administration of SDZ ICT 322, a
      selective 5-HT3 antagonist.
AB  - SDZ ICT 322, an indole-3-carboxylic acid scopine ester developed for the
      treatment of delayed gastric emptying, was administered in feed to four groups of
      14 male and 14 female Wistar rats at daily doses of 0, 5, 25 or 125 mg/kg/day for
      26 weeks. Clinical and periodic ophthalmic examinations, hematology, clinical
      biochemistry, and urinalysis were performed. Eyes were examined for
      histopathologic and electronmicroscopic alterations as well as for reduced
      glutathione (GSH) and oxidized glutathione (GSSG) levels. Skin effects with hair
      loss, hyperemia, and desquamation were found in the majority of the high-dose
      rats. At study termination, bilateral posterior lens opacities had developed in
      26 of the 28 high-dose rats. Histopathologically, grossly irregular and
      fragmented lens fibres were observed. Severe vacuolization of the lens epithelium
      was seen electronmicroscopically. The GSH/GSSG ratio was statistically
      significantly reduced in lenses of mid- and high-dose animals. Since decreased
      GSH/GSSG ratio is an established indicator for increased oxygen radical
      generation, these data suggest a possible role of oxidative stress in cataracts
      induced by SDZ ICT 322.

PMID- 8258394
TI  - Interferon alfa-2a in the treatment of exudative age-related macular
      degeneration.
AB  - Nineteen patients (20 eyes) with the exudative form of macular degeneration were
      treated with parenteral interferon alfa-2a. Fifteen patients (16 eyes) had
      adequate follow-up for evaluation of outcome of the exudative macular lesion. The
      average follow-up was 8 months (range 5-11 months). Color photographs and
      fluorescein angiograms were evaluated independently by two masked readers for
      change in size, presence of fibrosis, and leakage of the neovascular lesion.
      During the follow-up, none of the exudative lesions resolved: one lesion became
      smaller, four remained the same, nine enlarged, and two could not be graded based
      on the photographs. Visual acuity remained 20/40 or better in four eyes. The
      proportion of eyes with visual acuity of 20/200 or worse increased from 35% at
      the initial visit to 59% at the final visit. Ten patients experienced significant
      but reversible side effects, including weight loss, depression, and/or
      hematopoietic suppression. The data from these cases do not support any
      significant treatment benefit from interferon alfa-2a at the doses used in
      exudative macular degeneration.

PMID- 8258395
TI  - Perfluorocarbon liquids as postoperative short-term vitreous substitutes in
      complicated retinal detachment.
AB  - To avoid postoperative "compartmentalization" of the vitreous cavity, which can
      potentially accelerate the recurrence of proliferative vitreoretinopathy (PVR),
      32 eyes of 32 selected patients with complicated retinal detachment were managed
      with lensectomy, vitrectomy, 5-day internal tamponade with perfluorocarbon
      liquids (PFCL) and postoperative supine positioning until PFCL removal.
      Intraoperatively, 19 eyes had grade C3 or greater PVR; 10 eyes exhibited ocular
      trauma and 6 displayed giant tears. All but 5 patients (PFCL/fluid exchange)
      underwent PFCL/silicone oil exchange 5 days after surgery. Anatomic attachment of
      the retina was achieved with one operation in 25 (78%) of the 32 eyes with a
      median follow-up of 8 months (mean 8.4 months). Of the 20 eyes that underwent
      silicone oil removal, none redetached. Nineteen eyes (61%) showed no or only mild
      reproliferation; a macular pucker developed in 50% of the 20 eyes successfully
      reattached after PFCL/silicone oil exchange and in none of the 5 eyes
      successfully reattached after PFCL/fluid exchange. Intraocular tolerance of PFCL
      for up to 5 days of internal tamponade appeared to be good as judged by static
      threshold perimetry in the two patients tested and by our functional outcomes,
      with 88% of the reattached eyes showing a final visual acuity of 5/200 or better.

PMID- 8258396
TI  - Retinal separation, retinotomy, and macular relocation: I. Experimental studies
      in the rabbit eye.
AB  - An animal model in the rabbit eye was utilized to study mobilization and
      relocation of the fovea as a potentially beneficial surgical approach to age
      related macular disease. After lentectomy and vitrectomy, the retina was
      completely separated from the pigment epithelium by means of infusion into the
      subretinal space. A 360 degrees peripheral retinotomy was performed. The retina
      was rotated up to 60 degrees around the optic nerve as axis and reattached.
      Scanning and transmission electron microscopy revealed the relative intactness of
      outer segments and pigment epithelium after this procedure, both acutely and 3
      days following reattachment.

PMID- 8258397
TI  - Retinal separation, retinotomy, and macular relocation: II. A surgical approach
      for age-related macular degeneration?
AB  - Three cases of age-related maculopathy with severe and recent massive submacular
      hemorrhage were treated by performing complete vitrectomy. A total retinal
      detachment was created by infusion of fluid underneath the retina, followed by a
      peripheral circumferential retinotomy. This allowed access to the subretinal
      space for removal of blood and membranes and, more importantly, permitted
      rotation of the retina with relocation of the fovea. Rotations between 30 degrees
      and 80 degrees were achieved. One patient with 5 months' follow-up had a visual
      improvement from 1/200 to 20/80 and excyclorotation of images. The other two
      patients developed proliferative vitreoretinopathy after initially successful
      rotation. Their retinas were reattached after surgical removal of the membranes
      and silicone oil tamponade, but visual function remained low. The rationale for
      this treatment is that relocating the fovea to an area where pigment epithelium
      is less diseased than in the central area may allow for recovery of some useful
      vision.

PMID- 8258398
TI  - Peripapillary atrophy in unilateral capsular glaucoma.
AB  - Pairwise comparisons of peripapillary crescents and haloes were performed for 56
      eyes of 28 patients with early or moderate unilateral capsular glaucoma and no
      signs of exfoliation in the contralateral eye. The eyes differed highly
      significantly in rim area, rim/disc area ratio, cup area, and cup volume. They
      did not differ in disc areas, scleral ring areas, or size of peripapillary
      crescents. In the nonglaucomatous and glaucomatous eyes a significant correlation
      existed between the intraocular pressure (IOP) and the area of peripapillary
      atrophy. The area of peripapillary atrophy was significantly correlated with the
      damage to the glaucomatous optic nerve head. We concluded that the area of
      peripapillary atrophy is largely an inborn feature, and that nerve fiber loss can
      occur without differences in the peripapillary tissues. Nevertheless, an IOP
      induced change in the retinal pigment epithelium cannot be ruled out.

PMID- 8258399
TI  - Increased lipid peroxide levels and myeloperoxidase activity in the vitreous of
      patients suffering from proliferative diabetic retinopathy.
AB  - Lipid peroxide (LPO) levels, as determined by high-performance liquid
      chromatography (HPLC) and by the thiobarbituric acid (TBA) method, and
      myeloperoxidase (MPO) activity in vitreous of patients vitrectomized because of
      proliferative diabetic retinopathy were compared with LPO levels and MPO activity
      in vitreous of patients with no vitreoretinal proliferation. Both LPO levels and
      MPO activity were significantly elevated in the vitreous of patients with
      fibrovascular vitreoretinal proliferations secondary to diabetes. The TBA method
      produced higher values for LPO levels than did the HPLC method. The correlation
      between the two methods was 0.94. Our results suggest that both oxygen-free
      radicals and inflammation-related reactions can participate in the pathogenesis
      of diabetic retinopathy.

PMID- 8258401
TI  - Different regional changes of fluorescence spectra of clear human lenses and
      nuclear cataracts.
AB  - Fluorescence spectra are recorded from the cortex and nucleus of the same human
      lenses [clear and cataracta brunescens (nigra) with colorless cortex]. When
      comparing clear cortices with either the harder nucleus of a clear lens, or a
      cataracta brunescens for a given excitation wavelength, a shift of the
      fluorescence maxima of the nucleus to longer wavelengths is observed. The shift
      appears to be independent of the degree of coloring since it is very similar for
      different nuclei, and it is not increased in cataracta nigra. The fluorescence
      intensities are similar when comparing the clear cortex of clear lenses and
      cataracta brunescens. For the nuclei, however, the intensity increases by up to
      four to six times with increasing coloring. For constant excitation wavelength,
      the fluorescence band maximum of the nucleus (of clear lenses and of cataracta
      brunescens) exhibits roughly the same shift to longer wavelengths as that of the
      cortex. Upon 320 nm excitation the fluorescence intensity of a cataracta nigra is
      about twice that of a clear lens of juvenile age. Upon 380 nm excitation the
      factor increases to four. Therefore in older and colored lens nuclei a red shift
      of the fluorescence maximum with increasing excitation wavelength is observed. We
      discuss whether or not the changes in the molecular proteins, in addition to
      advanced glycolization end products, may be responsible for the different
      fluorescence properties (and the brown color) with increasing age.

PMID- 8258400
TI  - A removable ocular microdialysis system for measuring vitreous biogenic amines.
AB  - A microdialysis system with a removable probe and a fixed scleral entry port is
      presented. The probe can be inserted several times with minimal trauma,
      permitting repeated sampling in one animal. The functioning of the setup is
      illustrated by the measurement of dopamine, dihydroxyphenyl acetic acid, and
      noradrenaline in the vitreous of healthy rabbits under physiological conditions.

PMID- 8258402
TI  - 193-nm excimer laser sclerostomy using a modified open mask delivery system in
      rhesus monkeys with experimental glaucoma.
AB  - Excimer laser sclerostomy is a new glaucoma filtration procedure in which the
      argon fluoride excimer laser at 193 nm is delivered ab externo through a modified
      open mask system incorporating an en-face air jet to dry the target area and
      preserve hemostasis during ablation and a conjunctival plication mechanism, which
      allows the conjunctival and scleral wounds created by through-and-through
      ablation to separate once the mask is removed. No preparatory dissection of the
      conjunctiva is required. Five 200-microns and five 500-microns sclerostomies were
      formed by ablation at a pulse repetition rate of 20 Hz and a fluence per pulse of
      400 mJ/cm2 in fellow eyes of five rhesus monkeys with experimental glaucoma.
      Overall, seven of the ten eyes attained a functional result, with intraocular
      pressures remaining below 21 mmHg for 6 +/- 1 days and rising to the pre
      operative level after 10 +/- 3 days without adjunctive antifibroblast medication.
      The duration of filtration for 200-microns and 500-microns sclerostomies was
      similar, and parallels that previously observed for posterior lip sclerectomy in
      the same animal model. The three eyes with no functional result all had
      incorrectly positioned sclerostomies. Choroidal detachment and significant
      shallowing of the anterior chamber did not occur. Excimer laser sclerostomy
      appears to be a viable technique for filtration, provided that mask placement is
      accurate.

PMID- 8258403
TI  - Presumed septic emboli following dental extraction.

PMID- 8258404
TI  - Bacterial optic disk mass and toxoplasmic-like encephalitis in an HIV
      seropositive subject.

PMID- 8258405
TI  - A method for real-time intraocular pressure monitoring during scleral buckling
      surgery.

PMID- 8258406
TI  - Exposure to the light of an operating microscope.

PMID- 8258407
TI  - Stanley Chang 1992 recipient of the Hermann Wacker Prize of the Club Jules Gonin.

PMID- 8258408
TI  - The 'vapour-phase' migration of styrene from general purpose polystyrene and high
      impact polystyrene into cooking oil.
AB  - General purpose and high impact polystyrene (GPPS and HIPS, respectively) are
      used in many food packaging applications. In some packaging configurations, where
      there is no direct contact of a liquid surface with the polymer, 'vapour-phase'
      migration of styrene monomer from the polymer with subsequent absorption into
      food is thought to be a significant mode of transfer. Correlation of residual
      styrene concentrations in polystyrene with vapour-phase styrene migration is of
      interest in order to predict potential consumer exposure to styrene from food
      packaging applications of this configuration. Studies of the migration of styrene
      from GPPS and HIPS into air with subsequent absorption of the monomer into
      cooking oil, 'vapour-phase' migration, was determined in a sealed system. The
      results showed that for both polymers the amount of styrene migrating from the
      polystyrene and being absorbed by the oil was proportional to the square root of
      the time of exposure. The diffusion coefficients calculated for the vapour-phase
      migration of styrene from both polymers were found to be in good agreement with
      the diffusion coefficients previously determined for the 'liquid-phase' migration
      of styrene from similar polymers where the polymers were completely submerged in
      the cooking oil. These results indicate that the styrene concentrations measured
      in both experiments were attributable to the intrinsic diffusion of styrene from
      polystyrene, and that contact with cooking oil did not accelerate migration in
      previous experiments.

PMID- 8258409
TI  - Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca
      mulatta) monkeys. Part 1A. Prebreeding phase: clinical health findings.
AB  - A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average
      estimated age of 11.1 +/- 4.1 yr SD, were first randomly allocated to four
      similar test rooms (20 monkeys/room) and then randomly allocated to one of the
      five dose groups (four females/dose group/room). Each day, the females self
      ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor
      1254/kg body weight. After 25 months of daily dosing, approximately 90% of the
      treated females attained a qualitative pharmacokinetic steady state with respect
      to the concentration of polychlorinated biphenyl in their adipose tissue. The
      test monkeys were monitored daily for health and menstrual status, as well as
      feed and water consumption. On a weekly basis, each female's body weight was
      determined and a detailed clinical examination was conducted. Minor treatment
      effects included a slight, but not statistically significant, decrease in feed
      and water consumption as well as a decreased feed conversion ratio and a slight
      increase in the duration of menses. Statistically significant, dose-related
      treatment effects included inflammation and/or prominence of the tarsal
      (Meibomian) glands, eye exudate, and various finger and toe nail changes. These
      results were found at doses lower than those previously reported for non-human
      primates.

PMID- 8258410
TI  - Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca
      mulatta) monkeys. Part 1B. Prebreeding phase: clinical and analytical laboratory
      findings.
AB  - A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average
      estimated age of 11.1 +/- 4.1 yr SD were first randomly allocated to four similar
      test rooms (20 monkeys/room), and then randomly allocated to one of five dose
      groups (four females/dose group/room). Each day, the monkeys self-ingested
      capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body
      weight. After 25 months of daily dosing, approximately 90% of the treated females
      attained a qualitative pharmacokinetic steady state with respect to the
      concentration of polychlorinated biphenyl (PCB) in their adipose tissue.
      Subsequently, oestrogen and progesterone concentrations in serum were determined
      for one complete oestrous cycle and various immunological tests were conducted,
      while the monkeys continued to receive their daily dose of PCB. During the
      prebreeding phase of the study, blood for clinical and analytical monitoring
      including haematology, serum biochemistry, serum hydrocortisone, serum proteins
      (alpha 1, alpha 2, beta and gamma-globulins), serum immunoglobulins (A, G and M)
      and thyroid variables (thyroxine/triiodothyronine (T3) uptake ratio, percentage
      T3 uptake and free thyroxine index), were obtained monthly, as were specimens to
      ascertain the concentration of PCB in the blood, adipose tissue and faeces. Major
      findings among treated monkeys included the following: changes in haematology
      (decreased erythrocyte count, haematocrit, reticulocyte count, and mean platelet
      volume), serum biochemistry (decreased cholesterol and total bilirubin),
      immunotoxicity (decreased antibody production to sheep red blood cells and
      alterations in the percentage of T helper and T suppressor cells) and pathology
      (the number of regions of sebaceous gland lobules per unit of histological length
      was significantly reduced). These effects were observed at PCB doses lower than
      those previously reported for non-human primates.

PMID- 8258411
TI  - Carcinogenicity study of the emulsifier TOSOM and the release agent TOS in Wistar
      rats.
AB  - Groups of 60 Wistar rats of each sex were fed diets containing 3, 6 or 12% of the
      margarine emulsifier TOSOM (thermally oxidized soybean oil interacted with mono-
      and diglycerides of fatty acids) for 2.5 yr. In addition, three groups of 60 rats
      of each sex were fed two products of the release agent TOS (thermally oxidized
      soybean oil) in dietary levels of 1.2% TOS(G) (TOS from Grindsted Product A/S,
      Denmark) and 0.3 and 1.2% TOS(N) (TOS from Nexus Aps, Denmark), respectively for
      2.5 yr. 120 rats of each sex fed a diet containing mono- and diglycerides served
      as controls. The diets given to all groups were isocaloric. Clinical appearance,
      food consumption, body weight and weight gain, survival, haematology, and
      clinical chemistry parameters were examined. Gross and histopathological
      examinations, including neoplastic and non-neoplastic lesions, were performed on
      all groups. Time to occurrence of tumours was recorded. No substance-related
      effect, including carcinogenicity, was found.

PMID- 8258412
TI  - Effect of neomycin on the hydrolysis and toxicity of vicine and convicine in
      rats.
AB  - This study in the rat established the effects that a broad-spectrum and poorly
      absorbed antibiotic, neomycin sulfate, had on the in vitro and in vivo hydrolysis
      of vicine and convicine by the intestinal microflora, and on vicine- and
      convicine-induced depletion of blood glutathione and the resulting toxicity. The
      in vitro studies demonstrated that digesta from the caecum and large intestine
      were highly effective in hydrolysing vicine and convicine, whereas digesta from
      the same sections of the gastro-intestinal tract of neomycin-treated rats were
      much less effective (P < 0.0001). The in vivo studies showed that the total
      amount of vicine and convicine excreted in the urine and faeces was much greater
      in neomycin-treated rats compared with controls (P < 0.05), indicating the
      ability of neomycin to increase the amount of glycosides, particularly that of
      vicine, excreted in the faeces. The ability of glycosides to decrease the
      concentration of glutathione in blood (P < 0.05) and to increase rat mortality
      was greatly reduced in rats that were treated with neomycin, particularly in
      those treated ip with the toxin. Thus, the results demonstrated that neomycin
      reduced the rate at which vicine and convicine were hydrolysed in the lower
      section of the gastro-intestinal tract, and that neomycin treatment was
      associated with a reduced toxicity of the glycosides.

PMID- 8258413
TI  - Toxicity study of the main alkaloids of Datura ferox in broilers.
AB  - Seeds of the weed Datura ferox are frequent contaminants of raw materials used
      for animal feed. These seeds produce various toxic effects and contain mainly the
      alkaloids scopolamine and hyoscyamine. In this 3-month toxicity study, a mixture
      of scopolamine and hyoscyamine (98:2) was incorporated at four total alkaloid
      levels (1.5, 15, 75 or 150 mg/kg feed) into a control diet fed to 100 broilers.
      Alkaloid feeding caused significant reductions in the body weight gain of birds,
      especially of those fed a dose of 150 mg alkaloid/kg feed. Growth-retarding
      effects, however, were transient, as no changes in body weight gain were noted
      after 52 days of alkaloid feeding. Alkaloid-treated broilers showed no
      significant differences from controls with respect to the cardiac rate and
      breathing frequency nor in relation to plasma aspartate aminotransferase, alanine
      aminotransferase and alkaline phosphatase activities. In contrast, plasma leucine
      aminopeptidase activity was significantly reduced after 3 months in all alkaloid
      fed birds. Autopsy and histological examination of tissues by light and electron
      microscopy revealed no pathological changes associated with alkaloid feeding.
      Broilers appeared generally healthy and behaved normally throughout. These data
      should be considered in the formulation of new, improved regulations defining the
      maximum allowable alkaloid content of D. ferox seeds contaminating raw materials
      destined for use as broiler feed.

PMID- 8258414
TI  - Evaluation of the reproductive toxicity of gallium nitrate in mice.
AB  - Reproduction studies were performed with gallium nitrate, an antihypercalcaemic
      drug that is also used as a chemotherapeutic agent for the treatment of certain
      malignancies. Male mice were injected subcutaneously with gallium nitrate at
      doses of 0 (controls), 24, 48 and 96 mg/kg/day every other day for 14 days before
      mating with untreated females. Fertility and reproductive performance in the
      gallium nitrate-treated groups did not differ significantly from controls. No
      significant changes were observed in the relative testes and epididymis weights.
      Sperm counts in the gallium nitrate-dosed groups were comparable with those in
      the control group, whereas the percentage of motile cells was similar between
      treated and untreated animals. Histopathological examination of the testes and
      epididymis did not reveal any changes at any dose of gallium nitrate. The no
      observed-adverse effect level was 96 mg/kg body weight. This dose is about 30
      times higher than the current doses of gallium nitrate administered to humans.

PMID- 8258415
TI  - Preformed volatile nitrosamines in some Nigerian foodstuffs.
AB  - Some common Nigerian foodstuffs were assessed for their content of preformed
      volatile nitrosamine by chemiluminescence detection following gas chromatographic
      separation. Nitrosodimethylamine levels of between 0.4 and 4.6 ppb were detected
      in 75% of the samples analysed. The highest value was found in Brassica
      oleraceae, while Vernonia amygdalina contained the lowest detectable level. These
      data suggest that Nigerians may be exposed to chronic but very low levels of
      carcinogenic nitrosamines in their foods.

PMID- 8258416
TI  - Hepatic peroxisome proliferation in rodents and its significance for humans.
AB  - Peroxisomes are subcellular organelles found in all eukaryotic cells. In the
      liver they are usually round and measure about 0.5-1.0 microns; in rodents they
      contain a prominent crystalloid core, but this may be absent in newly formed
      rodent peroxisomes as well as in human peroxisomes. A major role of the
      peroxisomes is the breakdown of long-chain fatty acids, thereby complementing
      mitochondrial fatty-acid metabolism. Many chemicals are known to increase the
      number of peroxisomes in rat and mouse hepatocytes. This peroxisome proliferation
      is accompanied by replicative DNA synthesis and liver growth. No clear structure
      activity relationships are apparent. Many of these peroxisome proliferators
      contain acid functions that can modulate fatty acid metabolism. Two mechanisms
      have been proposed for the induction of peroxisome proliferation. One is based on
      the existence of one or several specific cytosolic receptors that bind the
      peroxisome proliferator, facilitating its translocation to the cell nucleus and
      the activation of the expression of specific genes. The second, perhaps more
      general, hypothesis involves chemically mediated perturbation of lipid
      metabolism. These two hypotheses are not mutually exclusive. Many peroxisome
      proliferators have been shown to induce hepatocellular tumours, despite being
      uniformly non-genotoxic, when administered at high dose levels to rats and mice
      for long periods. Three mechanisms have been proposed to explain the induction of
      tumours. One is based on increased production of active oxygen species due to
      imbalanced production of peroxisomal enzymes; it has been proposed that these
      reactive oxygen species cause indirect DNA damage with subsequent tumour
      formation. In rodents, an alternative mechanism is the promotion of endogenous
      lesions by sustained DNA synthesis and hyperplasia. Thirdly, it is conceivable
      that sustained growth stimulation may be sufficient for tumour formation. Marked
      species differences are apparent in response to peroxisome proliferations. Rats
      and mice are extremely sensitive, and hamsters show an intermediate response
      while guinea pigs, monkeys and humans appear to be relatively insensitive or non
      responsive at dose levels that produce a marked response in rodents. These
      species differences may be reproduced in vitro using primary culture hepatocytes
      isolated from a variety of species including humans. The available experimental
      evidence suggests a strong association and a probable casual link between
      peroxisome-proliferator-elicited liver growth and the subsequent development of
      liver tumours in rats and mice. Since humans are insensitive or unresponsive, at
      therapeutic dose levels, to peroxisome-proliferator-induced hepatic effects, it
      is reasonable to conclude that the encountered levels of exposure to these non
      genotoxic agents do not present a hepatocarcinogenic hazard to humans.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8258418
TI  - Mycotoxins in the diet.

PMID- 8258417
TI  - The Leon Golberg Memorial Lecture. Recent advances in toxicology relevant to
      carcinogenesis: seven cameos.

PMID- 8258419
TI  - [Phylogenetically old HIV-1 from Cameroon discovered. HIV-2 related virus
      isolate].

PMID- 8258420
TI  - [Interventional possibilities in diabetic nephropathy].

PMID- 8258421
TI  - [Otoacoustic emissions. A futuristic objective hearing test].
AB  - In a third of all persons with normal hearing, the inner ear emits sounds that
      are caused by movements of the hair cells. By applying an acoustic stimulus,
      otoacoustic emissions can be provoked in all healthy ears. These transitory
      evoked otoacoustic emissions (TEOAE) and the distortion products of otoacoustic
      emissions (DPOAE) can be utilized by two different procedures for testing
      hearing. The latter parameter reflects possible damage to the inner ear. Such
      hearing tests are quick, harmless, and can be performed irrespective of patient
      age. For this reason, they are particularly suitable for use in the screening of
      the newborn. In addition, they are also suitable for the early diagnosis of
      hearing impairment and the effects of ototoxic agents, as also for
      differentiating sensorineural hearing loss.

PMID- 8258422
TI  - [Bronchial asthma in childhood. Part 1: Clinical manifestations, diagnosis and
      ground rules of therapy].
AB  - The most common disease met with in childhood is bronchial asthma, the prevalence
      of which in Germany is reported to be as high as 8%. However, the true figure is
      likely to be considerably higher. Bronchial asthma is defined as a variable,
      episodic airways obstruction that is accompanied by hypercontractility of the
      bronchial system. Instead of the characteristic wheezing, in childhood the
      disease often presents as untypical attacks of coughing. In the differential
      diagnosis, aspiration of a foreign body, mucoviscidosis, tuberculosis, immune
      defects and an intrathoracic mass lesion must all be considered. The aim of
      treatment is to normalize pulmonary function and completely restore the child's
      physical robustness.

PMID- 8258423
TI  - [Weight reduction with alternative diets. Principles, philosophy, side effects,
      effectiveness. Part 10: Alternative diets (S)].

PMID- 8258424
TI  - [Treatment of migraine attacks with sumatriptan].
AB  - The serotonin agonist, sumatriptan, is a new, highly promising alternative
      treatment for migraine that has a vasoconstricting effect on the blood vessels
      dilated during an attack. In addition, sumatriptan inhibits the neurogen-mediated
      sterile inflammation associated with migraine. Its effects, pharmacological
      properties and side effects are discussed and considered in relation to its high
      price. The subcutaneous form of sumatriptan is indicated for use in attacks
      accompanied by initial violent vomiting, and the oral form for attacks in which
      standardised medication elicits either no response or side effects, as also to
      treat migraine that regularly renders the sufferer unable to work. When attacks
      are a frequent occurrence, migraine prophylaxis should first be initiated. The
      significance of cardiovascular side effects is interpreted, and hints provided on
      instructing the patient in the use of this drug.

PMID- 8258425
TI  - [The insane of Valencia. Comedy as the key to understanding mental healing in
      Spain during the "Golden Age"].

PMID- 8258426
TI  - [Status of therapy of HIV infections. A long way to standardized procedure].

PMID- 8258427
TI  - [Management of depressed patients by family physicians. Questionnaire study in
      Hamburg].
AB  - METHOD: With the aid of a questionnaire specially developed for the purpose,
      general practitioners were questioned about their management of depressed
      patients attending their offices. A number of physician-related aspects that
      might have been the cause of the differences in prevalence and management of the
      patients, were investigated. RESULTS: Estimations on the part of the physicians
      that patients with psychological problems accounted for some 20% of their total
      case load were in agreement with figures obtained from other studies. Those
      specifically with depression accounted for 8.6%. The practitioners' assessment of
      their own competence in caring for depressed patients, and their cooperation with
      other institutions play a key role in the incidence of the diagnosis and the
      nature of medical treatment--by means of drugs, psychotherapy, referral, yes or
      no. The results obtained suggest a need to improve the psychiatric training of
      general practitioners and for closer cooperation with neurologists,
      psychologists, and hospitals.

PMID- 8258428
TI  - [Weight reduction with alternative diets. Part 11: Alternative diets (Sch to W)].

PMID- 8258429
TI  - [Pharmacokinetics and -dynamics of retard formation of isradipine. Summary of
      studies].
AB  - The newly developed sustained-release form of isradipine (Vascal uno/Lomir SRO)
      releases the active substance continuously from a gel matrix over a period of 24
      hours. In comparison with the standard formulation, the absolute bioavailability
      of the sustained-release preparation is somewhat increased at about 22.5%.
      Maximum plasma levels are reached five to seven hours after oral administration
      of a capsule, and then level off. Both maximum plasma levels and bioavailability
      increase linearly with dose. At therapeutic dosage isradipine does not
      accumulate. Twenty-four hours after ingestion of the capsule, plasma levels are
      still half the maximum. As a result of slow absorption and minimal fluctuations
      in the concentration of the active agent, side effects of the sustained-release
      version of isradipine are even rarer than with the standard preparation.

PMID- 8258430
TI  - [Pregnancy and labor complications--their significance in the development of
      schizophrenic psychoses].
AB  - In a retrospective study of 80 chronic DSM III-R schizophrenics and 80 controls,
      the occurrence of obstetric complications (OCs) into the development of chronic
      schizophrenias was investigated using Leonhard's distinction in systematic
      schizophrenia (no obvious familial loading) and unsystematic schizophrenia
      (mainly genetically determined according to Leonhard). The Lewis & Murray and
      Fuchs scales were used for evaluation. In both scales, unsystematic
      schizophrenias did not differ from controls, but those with OCs were
      significantly (p < 0.01) earlier hospitalized (20.5 years) than those without OCs
      (25.6 years). Systematic schizophrenics had an increased frequency, severity and
      total score of OCs compared to controls in the Fuchs scale (p < 0.01). Likewise,
      in the Lewis & Murray scale systematic schizophrenia showed an increased presence
      of OCs compared to controls (p < 0.05) and to unsystematic schizophrenia (p <
      0.1). Systematic schizophrenias were significantly allocated to maternal
      infectious diseases during mid-gestation. Patients with maternal infections
      showed more additional OCs than those without (p < 0.05; Lewis & Murray scale).
      In systematic schizophrenia, a history of OC was not associated with an early
      onset of the disease. In the genetic determined schizophrenias prenatal and
      perinatal disturbances lead to an early onset of the disease, however, in
      systematic schizophrenias they seem to be of causal importance for the
      development of the disease.

PMID- 8258431
TI  - [Psychosocial development and problems in early adulthood: developmental
      psychological characterization of an important segment of the life cycle].
AB  - Young adulthood represents a genuine developmental phase in the life cycle. In
      its transitional position it shares many traits with the developmental process in
      youth and adulthood. Among its central developmental problems are: establishing a
      secure personal identity, forming mature friendships and mature intimate
      relationships, reorientation of family ties, building up a core of ideological
      values, selecting a long-term vocation, finding one's bearings, looking to the
      future. The perspective of "normative crisis" vs "continuous transformation" is
      discussed. Ths significance of the patterns of adaptation found in young
      adulthood for further psychosocial development is emphasized.

PMID- 8258432
TI  - [Couvade syndrome, a psychogenic illness in the transition to fatherhood].
AB  - More often than generally expected, men experience the transition to fatherhood
      as an emotional strain and become psychosomatically ill during their partner's
      pregnancy. This is known as the "couvade" syndrome. The psychogenic aetiology of
      these, for the most part unspecific somatic symptoms, mostly remains unknown to
      the treating doctors and the patients. On the other hand, psychiatric
      complications including psychotic illness can occur. In the following, the
      syndrome is described with an overview of the literature, and the aetiology is
      examined. In addition to the biographical causes, the ethnological-historical
      roots of the syndrome and possible therapeutic consequences are discussed.

PMID- 8258433
TI  - [New procedures in transesophageal echocardiography: multiplane transesophageal
      echocardiography and transesophageal stress echocardiography].
AB  - Multiplane transesophageal echocardiography is a new development in transducer
      technology, which allows by rotation of the transducer to obtain not only
      transverse and longitudinal planes but also all intermediate planes. Exterior
      control allows continuous rotation of the scanning plane from the conventional
      transverse plane, corresponding to 0 degree, to the longitudinal plane,
      corresponding to 90 degrees and further to a left-right inverted transverse
      plane, corresponding to 180 degrees. Although the echoscope tip, which houses the
      rotatable transducer, is slightly larger than conventional probes, in our
      clinical experience of well over 400 cases, intubation of the esophagus is not
      more difficult than with the mono- or biplane probe. In comparison with the
      biplane technique the adjustment of intermediate planes is easier and less
      unpleasant for the patient, since mechanical irritation due to sideward flexion
      of the probe is less often necessary. Plane rotation, effected by control buttons
      in the echoscope handle, takes eight seconds from 0 degree to 180 degrees. The
      probe incorporates a 5 MHz phased array transducer, which alternatively works at
      3.7 MHz. Pulsed, continuous and color Doppler are also integrated. Multiplane
      transesophageal echocardiography was used to investigate several clinical
      questions. In 41 patients with aortic valve stenosis the valve area was
      determined by planimetry. The valve area was measured in an individually aligned
      short axis view (between 50 degrees and 70 degrees). A high correlation (r =
      0.95; Y = 0.9 X + 0.1; p < 0.01) with invasively determined valve areas by the
      Gorlin formula was found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258434
TI  - [Biplane transesophageal echocardiography. Diagnostic improvement over the mono
      plane technique].
AB  - Monoplane transesophageal echocardiography (TEE) is a well established diagnostic
      tool of examination of great value in determining pathological changes in both
      atria, atrioventricular valves, the left-ventricular outflow tract, and in the
      thoracic aorta (Table 1). With the monoplane technique, however, it is never
      possible to obtain more than parallel, or oblique transverse views of the heart
      and surrounding vessels. The only means with which to examine anatomic structures
      in their cranio-caudal dimension by way of this method is to make a composite of
      a number of transverse sections. This makes three-dimensional interpretation of
      monoplane images difficult. The biplane transesophageal technique provides images
      of orthogonal sections to the transverse plane, allowing three-dimensional
      reconstruction and thus greatly improved insight into the cardial anatomy. By
      ante- or retroflection and lateral angulation of the probe, it becomes possible
      to see structures as a whole, the greatest dimension of which may not lie in the
      strictly sagittal section, but on a craniocaudal diagonal plane, e.g. the
      ascending aorta, or the aortic valve plane. The diagnostic gain of additional
      data through biplane TEE stems from its images of cardial structures, which
      remain either unsatisfactory or not attainable on monoplane examination (Table
      2). Above all this pertains to the superior vena cava in its longitudinal
      extension (Figure 6), the right-ventricular outflow tract with pulmonary valve,
      the longitudinal two-chamber view (Figure 3), and the CW-Doppler analysis in
      presence of tricuspid valve regurgitation (Figure 13). Transversal visualization
      of the aortic arch is only feasible by using biplane imaging technique (Figure
      12). Compared to the monoplane technique, it shows clearly more distinct views of
      the apex of the left ventricle (Figure 1), the atrial anatomy (Figures 5 and 6),
      and here in particular the pathology of interatrial septum (Figure 7), as well as
      the aortic valve and the ascending aorta (Figures 8, 10 and 11). By using the
      longitudinal imaging plane left atrial appendage can be seen without additional
      anteflection of the probe, thus, reducing stress to the patient during
      examination. The loss of an infinite range of planes available to the multiplane
      technique is a disadvantage, but this can usually be compensated by appropriate
      flecting of the probe and adequate simultaneous lateral angulation. The range of
      rotation of the probe in the multiplane method allows better three-dimensional
      imaging of anatomic structures and regurgitant jets than do the mono- and biplane
      techniques, and comparable data are often only attained under much longer
      examination with the biplane instrument.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8258435
TI  - [Diagnostic value of transesophageal echocardiography in diseases of the heart
      valve system].
AB  - Due to high resolution transesophageal echocardiography has been proven to have
      additional diagnostic benefits in valvular heart disease. The quantification of
      aortic and mitral valve insufficiency is possible by the use of semiquantitative
      methods. In aortic valve insufficiency the relation of the regurgitant jet width
      to the left ventricular outflow tract and in mitral valve insufficiency the
      relation of the regurgitant jet area to the left atrium are the parameters with
      the most accurate sensitivity. The main advantage of the method in this point is
      the rapid detection of morphological pathology at the valves. The development of
      multiplane transducers enhanced the quantification of aortic valve stenosis which
      is performed by planimetry of the orifice area in an ideal cross-section of the
      valve reached at a mean angle of 46 degrees. The high resolution image of mitral
      valve anatomy leads to the intraoperative use of the method during valve repair
      identifying inadequate surgical correction, which can be revised instantly.
      Visualization of the valvular and subvalvular mitral apparatus enables a more
      reliable indication for valvuloplasty by detecting the presence or absence of
      atrial thrombi and assessing the severity of calcification, the guide catheter
      and the balloon placement. Transesophageal echocardiography is the method of
      choice in the detection and measurement of vegetations and abscesses in infective
      endocarditis. Imaging an increasing extent of a vegetation during follow-up
      investigations can lead to the necessity of surgical intervention for preventing
      embolic events. The transesophageal approach especially in combination with color
      doppler flow imaging is superior to the transthoracic method in the detection of
      abscesses and secondary complications like communication to adjacent structures
      or implication of the mitral valve. In this point the use of multiplane probes
      permits a more accurate assessment of the extent and the spatial configuration of
      additional masses. Concerning valve prostheses the detection rate of vegetations,
      abscesses as well as degenerations of bioprostheses is higher using the
      transesophageal method than the transthoracic approach. Abscesses located near
      the right coronary sinus or in the ventricular septum are difficult to detect due
      to shadowing caused by prosthetic artefacts. The visualization of bioprostheses
      allows the measurement of the thickness of the leaflets which is necessary for
      the diagnosis of valve sclerosis or degeneration. In combination with color
      doppler flow imaging the method allows the differentiation of transvalvular and
      perivalvular regurgitation. The movements of the occluder can be imaged leading
      to a more reliable diagnosis of obstruction in combination with the trans
      thoracic use of doppler-methods.

PMID- 8258437
TI  - Incidence and management of dysrhythmias after Fontan procedure.
AB  - The modified Fontan procedure for univentricular heart disease results in the
      full spectrum of significant cardiac arrhythmias: tachycardias and bradycardias.
      The tachycardias are primarily supraventricular in origin: 1. atrial flutter, 2.
      primary atrial tachycardia, 3. atrial fibrillation, and 4. accelerated junctional
      rhythm or junctional tachycardia; however, ventricular tachyarrhythmias occur
      also, but less frequently. Bradycardia usually is a result of 1. sinoatrial node
      dysfunction resulting in junctional rhythm or 2. less commonly, atrioventricular
      conduction abnormalities, such as second degree and third degree atrioventricular
      block. Finally, the combination of atrial tachyarrhythmias and sinoatrial node
      dysfunction can occur in a small but significant number of patients after Fontan
      surgery. A complete array of medical and pacemaker therapeutic options is
      necessary for the physician to treat these difficult arrhythmias successfully.

PMID- 8258436
TI  - [Transesophageal echocardiography in patients with systemic arterial embolism].
AB  - The percentage of ischemic strokes or peripheral arterial embolism attributed to
      cardiogenic embolism is about 30% and 75%, respectively. Diagnostic work-up in
      patients with prior arterial embolism is of prognostic importance, because
      embolic events are often recurrent. Cardioembolic sources with major risk of
      embolism are atrial fibrillation, mechanical or biological heart valve
      prosthesis, left ventricular or left atrial thrombi, left atrial myxomas,
      bacterial endocarditis, nonbacterial thrombotic endocarditis and nonischemic
      dilative cardiomyopathies. Cardioembolic sources with minor risk of embolism are
      mitral valve prolapse, isolated mitral annular calcification, patent foramen
      ovale, atrial septal aneurysm and calcific aortic valve stenosis. Studies have
      shown that two-dimensional transthoracic echocardiography yields little useful
      information in patients with arterial embolism. The advent of transesophageal
      echocardiography in the late 1980s allowed a more reliable identification of
      potential cardioembolic sources. The close contact of the echoprobe in the
      esophagus to the heart allows better resolution of intracardiac structures,
      particularly when cardiovascular abnormalities at the atrial level, the base of
      the heart and the thoracic aorta are sought. We studied 153 patients with
      clinically suspected arterial embolism by transthoracic and transesophageal
      echocardiography. Patients with extracranial carotide occlusive disease and
      patients older than 60 years were excluded from the study. In 88 out of 153
      patients (58%) a cardioembolic mechanism could be detected by the combination of
      transthoracic and transesophageal echocardiography. Using the transthoracic
      method alone, a cardioembolic source could only be found in 55 patients (36%).
      Valvular heart disease and regional or global wall motion abnormalities could be
      visualized by both methods with similar results. However, only two out of 22 left
      atrial thrombi detected by transesophageal echocardiography could be documented
      also with the transthoracic approach. Transesophageal echocardiography was
      superior in the evaluation of valvular vegetations, intracardiac tumors, diseases
      of the thoracic aorta and abnormalities of the interatrial septum. Only left
      ventricular thrombi could be better evaluated by the transthoracic method,
      because visualization of the left ventricular apex by the transesophageal
      approach is problematic. In patients with systemic arterial embolism the
      combination of transthoracic and transesophageal echocardiography is the
      diagnostic method of choice to detect a cardioembolic source. Randomized studies
      in the future must prove, whether the echocardiographic findings can lead to
      better therapeutic strategies to improve the prognosis of patients with embolic
      disease.

PMID- 8258438
TI  - Digital models for arterial pressure and respiratory waveforms.
AB  - Digital models for arterial pressure pulse (APP) and respiratory volume waveforms
      (RVW) are proposed for efficient representation of these signals. When these
      signals are discrete cosine transformed (DCT), the pole-zero technique of
      Steiglitz-McBride (SM) gave system functions of much lower order than those
      obtained directly from the signals. The DCT of a bell-shaped biphasic wave needed
      two poles and two zeros. Based on this, the model order is fixed by the number of
      distinct peaks in the magnitude spectrum of the transformed APP/RVW signal. The
      partial fraction expansion (PFE) of the system function allowed delineation of
      component waves present in the time signal. The angles of model poles and zeros
      enabled easy determination of several important features from both of these
      signals. The model performance is evaluated using the normalized root mean-square
      error (NRMSE). A Bayes classifier using the pole angles as the feature vector
      performed satisfactorily when a limited number of RVW's recorded under deep and
      rapid maneuver are classified into normal (n) and abnormal (ab) categories of
      respiratory pathways.

PMID- 8258439
TI  - Selection of myocardial electrogram features for use by implantable devices.
AB  - Implantable devices that terminate ventricular tachycardia must be capable of
      correctly classifying heart rhythms to a high degree of reliability. We evaluated
      the relative discriminating power of several myocardial electrogram (ME) features
      in six human subjects by reducing the order of their corresponding feature spaces
      using three different optimization methods: 1) minimizing univariate Bayes error
      rates (univariate parametric), 2) maximizing the Kullback divergence
      (multivariate parametric), and 3) pruning classification trees (nonparametric).
      We found that although the composition of the optimal subspaces varied
      considerably from one subject to another, one frequency domain feature was common
      to most of the optimal subspaces.

PMID- 8258440
TI  - EView--a workstation-based viewer for intensive clinical electroencephalography.
AB  - We describe a workstation-based EEG viewer that satisfies the requirements for
      high-volume clinical EEG review. It currently supports two 24-h four-bed epilepsy
      monitoring units and a network of routine, intraoperative, and intensive care
      monitors, providing paperless review of over 5000 pages/day by a staff of
      clinical neurophysiologists. The design takes advantage of the development
      environment, processing and graphics resources, and networking capabilities of
      high-performance UNIX workstations. The user interface and operational
      infrastructure have been tailored to the demands of clinical neurophysiologists
      requiring rapid access to large volumes of EEG waveform data in a large clinical
      neurophysiology laboratory. This paper describes the functional requirements,
      system architecture, and implementation details of the current system.

PMID- 8258441
TI  - 3-D computation of E fields by the volume-surface integral equation (VSIE) method
      in comparison with the finite-integration theory (FIT) method.
AB  - An algorithm has been developed for calculation of 3-dimensional E fields by the
      volume-surface integral equation (VSIE) method. Integration over surface elements
      is performed by elementary analytical formulas, assuming a linear interpolation
      of surface charges. Grid points at electrical interfaces are split off, well
      considering the E field behavior at these contours, specifically at sharp bends
      and multimedia junctions. Averaging procedures are utilized in order to avoid
      undefined or infinite values at critical points. The VSIE is solved by iteration
      using GMRES ("general minimum residuum") solver on a SUN workstation SPARC-IPX or
      Cray XMP, whereby convergence speed decreases considerably as the heterogeneity
      of the problem increases. Computation time (e.g., 20 min on a supercomputer for
      approximately 30,000 cells) needs to be reduced by further code development.
      Results for 3-D test cases (plane wave illuminating a layered cylinder) generally
      agree well with the finite-integration-theory (FIT) method if high E field
      gradients occur perpendicular to electrical boundaries. The VSIE method predicts
      slightly higher E fields only in critical regions. On the other hand, the FIT
      method at present is more efficient with respect to computation time for large
      domains with high cell numbers (> 100,000 cells).

PMID- 8258442
TI  - Two-dimensional electrophoresis image interpretation.
AB  - A novel method to interpret two-dimensional electrophoresis gels is presented.
      Genetic background and electrophoretic processes are summarized. Present methods
      to analyze gel images and to exploit series of gels are described, then their
      drawbacks are outlined. Artificial Intelligence techniques are introduced to
      build an image interpretation system which can compensate for certain failures of
      present methods and augment their efficiency. By reproducing methods of
      biological experts, this system automatically identifies proteins--whether
      isolated or inside constellations--on an electrophoretic gel. This system is
      based on a modular architecture, featuring image processing procedures, which
      allows extraction of parameters on the image and a top-down and bottom-up
      reasoning process. The reasoning process first matches extracted parameters to
      possible geometric models of proteins; it then returns to the image to determine
      possible missing elements on the gel. A prototype of this system was implemented
      and tested on plasma gels to identify apolipoproteins.

PMID- 8258443
TI  - Calculations of heating patterns of an array of microwave interstitial antennas.
AB  - In this paper, the heating (temperature) distribution patterns of an array of
      uniformly and step-insulated interstitial antennas located in inhomogeneous
      tissue and cancerous regions of the human body are calculated. Specifically, the
      bioheat equation, which takes into account various heat exchange mechanisms such
      as blood flow rate, heat conduction, and metabolic heat generation, was solved
      using the finite difference method, while the electromagnetic power absorbed
      (SAR) in the tissue region heated using an array of interstitial antennas was
      determined using the finite-difference time-domain (FDTD) method. Numerical
      results showing the validation of the developed computer program are presented,
      and the effect of varying parameters such as the blood flow rate on the resulting
      heating rate and patterns are examined. Possible clinical implementation of the
      developed temperature distribution-EM power deposition pattern computer code in
      treatment planning is described.

PMID- 8258444
TI  - Theoretical and measured electric field distributions within an annular phased
      array: consideration of source antennas.
AB  - The magnitude of E-field patterns generated by an annular array prototype device
      has been calculated and measured. Two models were used to describe the radiating
      sources: a simple linear dipole and a stripline antenna model. The stripline
      model includes detailed geometry of the actual antennas used in the prototype and
      an estimate of the antenna current based on microstrip transmission line theory.
      This more detailed model yields better agreement with the measured field
      patterns, reducing the rms discrepancy by a factor of about 6 (from approximately
      23 to 4%) in the central region of interest where the SEM is within 25% of the
      maximum. We conclude that accurate modeling of source current distributions is
      important for determining SEM distributions associated with such heating devices.

PMID- 8258445
TI  - Optimal application of high-frequency ventilation in infants: a theoretical
      study.
AB  - A recent multicenter study of preterm infants concluded that high-frequency
      ventilation (HFV) applied at 15 Hz, in comparison with conventional mechanical
      ventilation (CMV), did not lead to reduced incidence of barotrauma, contrary to
      previous expectations. The primary goal of the present theoretical study was to
      determine whether computed estimates of lung pressures during HFV and CMV are
      consistent with these findings. An existing theoretical model of lung mechanics
      and gas transport in HFV was modified for applicability to neonates. New
      features, such as expiratory flow limitation and pulmonary air leak, were also
      incorporated. Simulations with the model were conducted assuming combinations of
      frequency and tidal volume that maintained a constant level of eucapnia. We found
      that peak alveolar pressures and the magnitude of alveolar pressure swings
      resulting from HFV at 15 Hz were in general comparable to those produced by CMV
      in healthy neonates and infants with bronchopulmonary dysplasia; peak alveolar
      pressures in the latter group tended to be higher with HFV than in CMV.
      Application of HFV at 15 Hz was even less advantageous than CMV when pulmonary
      air leak was also present in the infants with bronchopulmonary dysplasia.
      However, the model predicted the existence of an optimal range of frequencies
      between 2 and 4 Hz in which alveolar pressure swings and peak alveolar pressures
      could be minimized, and in some cases, reduced below the levels produced by CMV.

PMID- 8258446
TI  - A minimal input-output configuration for a priori identifiability of a
      compartmental model of leucine metabolism.
AB  - To develop a model describing the structure and function of a metabolic system
      using data from an input-output experiment, it is useful to design a pilot tracer
      study first which contains a predicted maximal amount of information. Having
      postulated a physiologically reasonable model structure from the pilot data, two
      questions arise. First, are the model parameters a priori uniquely identifiable?
      That is, assuming an error-free model structure and data, can the parameters be
      uniquely identified from the information content of the pilot experiment? Second,
      if the model parameters are uniquely identifiable, is the pilot experiment a
      minimal one? That is, is the pilot experiment necessary and sufficient, in the
      sense of information content, among feasible experiments to guarantee a priori
      unique identifiability? The purpose of this paper is to determine a minimal input
      output configuration for the a priori unique identifiability of a compartmental
      model describing the metabolism of leucine, an essential amino acid. The original
      pilot tracer experiment was a two-stage experiment consisting first of a two
      input-five output experiment followed by a single input-single output experiment.
      Here we show to guarantee a priori unique identifiability of the leucine model
      that the single input-single output experiment is not necessary, and that two of
      the outputs of the multi-input-multi-output experiment are not required.

PMID- 8258447
TI  - Simultaneous measurement of intracellular calcium and electrical activity from
      patterned neural networks in culture.
AB  - Multisite extracellular electrical activity and intracellular calcium were
      recorded simultaneously. Electrical signals were measured using microelectrode
      array substrates. A novel cell positioning technique was combined with a method
      for controlling neurite outgrowth, which allowed cell-electrode contacts to be
      established easily, thus facilitating the electrical recording. Intracellular
      calcium was measured optically using the indicator fluo 3. Under low-magnesium
      conditions, cultured rat cortical neurons showed periodic transients of fluo-3
      fluorescence, which were synchronized with the periodic bursting observed
      electrically. The intervals between bursts could be determined by electrical
      stimulation through the substrate electrodes. The results suggest that functional
      synaptic connections are formed in the culture system.

PMID- 8258448
TI  - Reflectance pulse oximetry measurements from the retinal fundus.
AB  - Conventional transmission pulse oximetry is a noninvasive technique for the
      continuous monitoring of arterial oxygen saturation (SaO2) from peripheral
      vascular beds such as the finger tip or earlobe. In this paper we propose to
      exploit the unique transparency of the ocular media to make reflectance pulse
      oximetry measurements on the retinal fundus. This technique potentially offers
      significant advantages over conventional pulse oximetry, primarily the ability to
      monitor cerebral, as opposed to peripheral, oxygen saturation. We have developed
      an in vitro system to stimulate the retinal circulation and ocular optics. This
      system consists of a flexible cuvette located in a model eye and an
      extracorporeal blood circuit to stimulate arterial blood flow. The system was
      used to investigate the relationship between SaO2 and the R/IR ratio in
      reflectance pulse oximetry. To enable in vivo measurements to be made, we also
      modified a standard haptic contact lens to hold the pulse oximeter probe in front
      of the pupil. In a preliminary study, the lens was fitted to an awake volunteer
      and cardiac-synchronous signals were detected by the retinal pulse oximeter.

PMID- 8258449
TI  - Bioelectric impedance measurements using synchronous sampling.
AB  - We have applied synchronous sampling to the demodulation of bioelectric impedance
      signals. This overcomes the need for analog demodulators in bioimpedance
      measurements. The sampling rate is determined by signal bandwidth, rather than by
      the highest frequency component before demodulation.

PMID- 8258450
TI  - AC instrumentation amplifier for bioimpedance measurements.
AB  - We analyze the input impedance and CMRR requirements for an amplifier for
      bioimpedance measurements when considering the capacitive components of the
      electrode-skin contact impedance. We describe an ac-coupled instrumentation
      amplifier (IA) that, in addition to fulfilling those requirements, both provides
      interference and noise reduction, and yields a zero phase shift over a wide
      frequency band without using broadband op amps.

PMID- 8258451
TI  - Analysis of arterial waves by the single-pulse-response method.
AB  - This study introduces an improved method to determine experimentally the
      characteristic arterial impedance, and the forward and backward wave components
      in the carotid artery of the rabbit. This method is based on the concept of the
      "single-pulse response," i.e., the pressure and flow responses to a single
      cardiac contraction.

PMID- 8258452
TI  - Optimal detection, classification, and superposition resolution in neural
      waveform recordings.
AB  - The effects of noise autocorrelation on neural waveform recognition (detection,
      classification, and superposition resolution) are investigated in this study
      using microelectrode recordings from the cortex of a monkey. Optimal waveform
      recognition is accomplished by passing the data through a whitening filter before
      matched filtering for detection or template matching for classification and
      superposition resolution. Template matching without whitening requires about 40%
      higher signal-to-noise ratio than template matching with whitening for comparable
      classification and superposition resolution. The comparable difference for
      detection is 15%.

PMID- 8258453
TI  - An image processing scheme to quantitatively extract and validate hyoid bone
      motion based on real-time ultrasound recordings of swallowing.
AB  - An image processing technique with associated hardware was developed to
      quantitatively extract hyoid bone motion from realtime submandibular ultrasound
      images recorded during the swallowing act. Videofluorographic imaging, the "gold
      standard" of swallowing studies, was recorded simultaneously and synchronized to
      the ultrasound. Hyoid position obtained from the ultrasound was validated based
      on the videofluorography using personal computer-based image processing methods.

PMID- 8258454
TI  - Role of cathepsin D in the degradation of human serum albumin by peritoneal
      macrophages and veiled cells in antigen presentation.
AB  - Murine peritoneal macrophages (PMO) and veiled cells (VC) isolated from the
      thoracic duct of irradiated lymphadenectomized (MNLX) mice presented intact human
      serum albumin (HSA) to stimulated T lymphocytes, but VC were not as effective as
      PMO in presenting the antigen. Pepstatin A significantly inhibited the
      presentation of HSA by VC. Lysates prepared from PMO degraded [125I]HSA at pH 4.0
      to peptides as demonstrated by SDS-polyacrylamide-gel electrophoresis and
      autoradiography. Degradation was inhibited by pepstatin A, suggesting that
      cathepsin D might be responsible for processing the antigen. In contrast, lysates
      prepared from VC did not degrade [125I]HSA. The localization of cathepsin D, by
      light microscopy, was examined on cytospins of PMO and VC by means of a
      peroxidase antiperoxidase technique (PAP). Cathepsin D was found in vacuoles in
      the cytoplasm of PMO and, in some cases, appeared to be bound to some areas of
      the cell surface, but the enzyme could not be detected in VC.

PMID- 8258455
TI  - Immunoreactive fucosylceramide as a B-cell differentiation marker.
AB  - The reactivity of PC47H, a monoclonal antibody (mAb) directed against
      fucosylceramide, with cells of lymphoid lineage was examined. Immunoreactive
      fucosylceramide (FC) was recognized only in pokeweed mitogen (PWM)-stimulated B
      blasts, plasma cells and germinal center cells. mAb PC47H did not react with T
      cells at different stages or with peripheral blood B cells. Furthermore, FC was
      expressed abundantly in blastic cells of B-cell lymphoma, multiple lymphoma and
      myeloma cell lines KMS-12-BM and KMS-12-PE. In other words, FC was expressed more
      strongly in mature than in immature B cells. Immunoelectron microscopy showed
      that FC was located in the plasma membrane and rough endoplasmic reticulum. mAb
      PC47H can therefore be used as a unique B-cell differentiation marker for study
      of B-cell activation and differentiation and clonal analysis of lymphoid
      malignancies.

PMID- 8258456
TI  - Time-dependent changes of LAK cell phenotypes correlate with the secretion of
      different cytotoxic proteins.
AB  - Human lymphokine-activated killer (LAK) cells were generated from peripheral
      blood lymphocytes (PBL) of normal volunteers by interleukin-2 (IL-2) stimulation
      for 1-8 days. During the first 3 days the surface marker CD16 characteristic for
      natural killer (NK) cells was expressed and later the CD3 marker characteristic
      for cytotoxic T cells became predominant. The conditioned media of LAK cells
      collected after interaction of LAK cells with K562 target cells was
      chromatographically separated into two cytotoxic fractions: F1 and F2. It was
      demonstrated that fraction F1 contained cytotoxic proteins having molecular
      weights of 30 and 40 kDa, and fraction F2 contained cytotoxic proteins having
      molecular weights of 22, 38 and 75 kDa. The presence of the proteins in each of
      these two fractions correlated with the phenotype changes of LAK cells: the F2
      cytotoxic proteins were characteristic for NK-like cells, and the F1 proteins for
      cytotoxic T-lymphocyte (CTL)-like phenotypes.

PMID- 8258457
TI  - Transcriptional activation of the interleukin-6 gene by HTLV-1 p40tax through an
      NF-kappa B-like binding site.
AB  - The interleukin-6 (IL-6) gene is expressed by various stimuli including cytokines
      or viral infections, such as human T-cell leukemia virus type I (HTLV-1).
      However, it has not been well established how HTLV-1 induces the expression of
      the IL-6 gene. In the present study, we demonstrated that HTLV-1-derived
      transactivator protein, p40tax, could stimulate endogenous IL-6 gene expression.
      Furthermore, we showed that the NF-kappa B binding site (IL-6 kappa B site)
      located between -74 and -62 upstream of the cap site of the IL-6 gene was an
      essential cis-acting element for p40tax-mediated transactivation of the IL-6 gene
      expression by utilizing a series of 5' deletion mutants of the IL-6 5' flanking
      region as well as a construct with a mutated IL-6 kappa B site. We identified the
      presence of two nuclear factor complexes that bound to the IL-6 kappa B site. One
      was constitutively expressed, and the other was inducible by p40tax. Taken
      together, HTLV-1 p40tax directly induces IL-6 gene expression through the IL-6
      kappa B site, indicating the close association between IL-6 overproduction and
      HTLV-1 infection.

PMID- 8258458
TI  - Heterogeneity of helper T cell subsets in Peyer's patches.
AB  - The OX22 monoclonal antibody recognizes the high molecular weight form of the
      CD45 molecule on rat T cells encoded by the CD45RC exon of the leukocyte common
      antigen gene. Its expression on CD4+ T cells is associated with virgin unprimed
      cells and primed cells which produce IL-2 and IFN-gamma on stimulation and
      participate in cell-mediated immune reactions. This suggested that CD45RC
      expression may be useful as a phenotypic marker for cells expressing Th1
      function. In view of our previous data indicating heterogeneity of T-cell helper
      function in different lymphoid compartments in the gut, the helper activity of
      OX22-enriched or OX22-depleted cell populations prepared from Peyer's patches
      (PP) of rats was compared. Following intestinal immunization with keyhole limpet
      haemocyanin, PP cells were isolated and separated by panning. Recovery data
      indicated that the majority of T cells in rat PP express the OX22+ phenotype and,
      after separation, the OX22-enriched population contained 4 times as many cells as
      the OX22-depleted population. Functional studies revealed that both subsets were
      capable of providing cognate help for secondary IgM, IgG and IgA antibody
      responses indicating that on this basis the CD45RC marker does not correlate with
      Th1 function in rats.

PMID- 8258459
TI  - Limited heterogeneity of T-cell receptor V beta gene expression in the early
      stage of insulitis in NOD mice.
AB  - Non-obese-diabetic (NOD) mice spontaneously develop type I diabetes. The disease
      starts with T cells infiltrating the islets of Langerhans. We therefore examined
      the T-cell receptor (TCR) V beta region repertoire in islet infiltrates from
      individual female NOD mice from 4 to 10 week old by polymerase chain reaction
      (PCR) using V beta 1-V beta 17 specific oligonucleotides. The study revealed a
      limited heterogeneity of TCR V beta transcripts with a predominance of V beta 1
      at the onset of insulitis, i.e. at 4 weeks of age. The TCR VDJ beta sequences of
      the V beta 1 PCR fragments were identical in most of the individual mice. Among
      several different mice, similarities in the beta-junctional regions were
      detected. In contrast, a large heterogeneity of TCR V beta usage was found in
      mice with advanced insulitis, i.e., from 6 weeks of age on. Thus, these data
      suggest a limited heterogeneity of TCR V beta usage with a predominance of V beta
      1 at the initiation phase of the disease.

PMID- 8258460
TI  - Phenylarsine oxide (PAO) blocks antigen receptor-induced calcium response and
      tyrosine phosphorylation of a distinct group of proteins.
AB  - Antigen receptor (AgR) crosslinking by antigens or AgR-specific antibodies
      induces a cascade of enzymatic events in lymphocytes which involves activation of
      several non-receptor tyrosine- and serine/threonine kinases, phosphatases,
      phospholipases, etc. Here we show data demonstrating that a thiol group-reactive
      protein tyrosine phosphatase (PTP) inhibitor, phenylarsine oxide (PAO), uncouples
      a crucial part of the signaling events induced by anti-IgM or anti-Leu-4 (CD3) in
      human tonsil B lymphocytes, BL41 and Daudi B cell lines and Jurkat T lymphoma
      cells. PAO treatment (10 microM) resulting in distinct modification of AgR
      induced tyrosine phosphorylation pattern inhibited the AgR-mediated calcium
      response (Ca++ release and influx) of all of these cells completely. Since this
      treatment did not alter the cell viability and the binding capacity of the AgR
      crosslinking antibodies, alteration of the tyrosine phosphorylation pattern and
      blockage of the calcium response indicate prompt inactivation of essential signal
      transduction element(s).

PMID- 8258461
TI  - Cross-reactivity of 75 monoclonal antibodies to human immunoglobulin with sera of
      non-human primates.
AB  - We systematically analyzed a panel of 75 murine monoclonal antibodies (mAbs)
      reactive with human immunoglobulins IgG, IgA, IgM, IgD, and kappa and lambda
      light chains for reactivity with serum immunoglobulins of higher primates. In the
      great apes, and to a lesser extent in other primates, epitopes related to human
      light chains, IgM, IgA, IgD, and all 4 IgG subclasses were identified with many
      of the mAbs. Those mAbs identified as reactive with a given species may be useful
      for immunologic studies of these species. Cladistic analysis of antigenic
      relatedness generated a phylogenetic tree consistent with current anatomic or
      molecular taxonomies.

PMID- 8258462
TI  - Responses of human fetal splenocytes and thymocytes to interleukin-2 and
      comparison with adult peripheral blood lymphocytes.
AB  - By means of cytotoxicity and thymidine uptake assays, the effect of human
      recombinant interleukin-2 (rIL-2) on the induction of lymphokine-activated killer
      (LAK) cell activity and cellular proliferation in splenocytes and thymocytes from
      human fetuses (18-22 weeks) was studied and compared with that in mononuclear
      cells from adult peripheral blood. It was shown that the fetal splenocytes and
      thymocytes incubated with low doses of rIL-2 (10-100 U/ml) developed a broad
      spectrum of antitumor activity (LAK cytotoxicity), although the kinetics and
      magnitudes of the responses were different. It was also suggested that LAK
      precursors were present in fetal spleen and thymus. Furthermore, rIL-2 induced a
      stronger proliferative and cytotoxic response in splenocytes than in thymocytes.
      The human fetal LAK cells isolated from the spleen were found to be 10-20 times
      more potent than those from adult peripheral blood with regard to cell
      proliferation and cytotoxicity in vitro.

PMID- 8258463
TI  - Perturbation of in vitro HIV pathogenic effects by peptides showing sequence
      similarities with the C2 conserved domain of gp120.

PMID- 8258464
TI  - Intracellular processing of hapten-modified protein for MHC class I presentation:
      cytoplasmic delivery by pH-sensitive liposomes.
AB  - Phagocytic or endocytic uptake of pH-sensitive liposomes has been shown to result
      in the release of entrapped material into the cytosol. This system can therefore
      be applied to the targeted delivery of protein antigens into the MHC class I
      presentation pathway of antigen-processing cells. We have used trinitrophenyl
      (TNP)-modified chicken ovalbumin encapsulated in liposomes to examine the
      intracellular processing of haptenated proteins and the presentation of TNP
      modified peptides to MHC class I-restricted hapten-specific CTL. Here, we
      demonstrate for the first time that hapten-modified proteins can undergo
      intracellular processing by macrophages, that similar peptides are produced in
      the form of unmodified or haptenated derivatives, and that TNP-peptides are
      transported to the cell surface and presented to class I-restricted CTL via the
      ER/Golgi pathway. This system can now be used to study T-cell responses to
      naturally processed hapten-conjugated peptides in vitro and in vivo.

PMID- 8258466
TI  - Radiation: an alternative agent for pleurodesis.
AB  - Radiotherapy as an alternative agent has been tried for pleurodesis in four
      proven cases of adenocarcinoma of the lung. This non-invasive technique appears
      to be beneficial, however, this requires further trials.

PMID- 8258465
TI  - Comparative efficacy of oral sustained released bronchodilator in stable
      asthmatics.
AB  - Double blind randomized trial of oral conventional and sustained release
      bronchodilators was undertaken to observe comparative efficacy in 30 patients
      older than 15 years. All cases selected were stable asthmatics at least for last
      2 years having FEV1 improvement > or = 20%. Basal Pulmonary functions like FEV1,
      FVC and PEFR were recorded before and after drug administration at 1/2, 1, 2, 3,
      4, 6, 8, 10, 12 and 24 hours. Four drug regimens were given as a single dose in
      the morning on randomized crossover manner on 1st, 4th, 7th and 10th days,
      sustained release theophylline 300 mg+salbutamol 4 mg (Drug I), salbutamol 4 mg +
      theophylline 300 mg (Drug II), salbutamol sustained released (asthalin SA) 8 mg
      (Drug III), salbutamol sustained released (ventorlin CR) 8 mg (Drug IV). Mean
      FEV1 changes observed at 0, 6 and 12 hours for all the drugs were compared which
      showed no statistical significance (t = 2.3876). Therefore, we conclude that
      using single dose fixed combination of oral salbutamol and aminophylline either
      in a plain or slow released form have no additive bronchodilator effect as
      compared to salbutamol alone in stable asthmatics.

PMID- 8258467
TI  - Diagnostic methods for tuberculosis.
AB  - Tuberculosis (TB) is a major public health problem especially in the third world
      countries. In India, it is estimated that at present there may be approximately
      10 million persons suffering from radiologically evident pulmonary TB of whom
      about 2.5 million would be sputum positive. The number of deaths due to
      tuberculosis is estimated to be approximately 5,000,000 every year. Definitive
      diagnosis of tuberculosis depends on smear examination and culture of appropriate
      biological fluids. Only up to 50% of pulmonary and 25% of extrapulmonary TB are
      diagnosed by smear examination. Traditional culture methods take around 6 weeks
      before the diagnosis can be established. Chemotherapy for tuberculosis is
      prolonged, expensive and not free from serious side effects. If the diagnosis of
      TB is delayed, it leads to increases morbidity and in some cases mortality (e.g.
      tuberculous meningitis). Often the clinicians have to start therapy empirically.
      There is a great need, therefore, for tests which are highly sensitive and
      specific as well as rapid.

PMID- 8258468
TI  - An unusual foreign body in tracheobronchial tree: removed by fiberoptic
      bronchoscope.
AB  - Tracheostomy is a life saving procedure and many a times patients are discharged
      with permanent tracheostomy tubes. Rarely, a tracheostomy tube may break and
      enter the tracheobronchial tree. We present a case of an adult female in whom the
      broken tracheostomy tube entered the right main bronchus and was removed by
      fiberoptic bronchoscopy under topical anaesthesia.

PMID- 8258469
TI  - Fractured polyvinyl chloride tracheostomy tube as a foreign body in
      tracheobronchial tree.

PMID- 8258470
TI  - Hydropneumothorax secondary to hydatid lung disease.
AB  - A case of pulmonary hydatid disease which ruptured to produce a hydropneumothorax
      is reported. Radiologically the patient presented with an oval opacity which
      enlarged with an appearance of air crescent. Diagnosis was established by
      cytological examination of aspirated pleural fluid and an histopathological
      examination of tissue found in the drainage tube. The patient was managed
      conservatively with intercostal drainage, albendazole therapy and other
      supportive measures.

PMID- 8258471
TI  - Tuberculous mainstem bronchostenosis in a ten-year-old girl.
AB  - Tuberculous bronchostenosis involving the main bronchus is rare in children. We
      describe a 10-year-old girl who developed left mainstem tuberculous
      bronchostenosis inspite of effective and adequate chemotherapy for which she
      underwent a left pneumonectomy.

PMID- 8258472
TI  - Intra--arterial chemotherapy in the management of advanced maxillary sinus
      cancer.
AB  - Presented is an update on the current role of intra-arterial chemotherapy in the
      management of advanced maxillary sinus cancer. The potential benefit of such
      chemotherapy is that it permits the delivery of a high concentration of the
      cytotoxic agent directly to the tumour tissue bed in an effort to maximize the
      cytotoxicity and minimize the side effects. In such circumstances it is feasible
      to omit mutilating surgery and treat under an organ-sparing protocol without
      compromising survival.

PMID- 8258473
TI  - Acinetobacter meningitis.
AB  - 10,468 CSF samples from cases of meningitis in different age groups were cultured
      during 1988-1991. Acinetobacter calcoaceticus was isolated in 12 (5.6%) of 211
      positive cultures. The strain were 100% resistant to ampicillin, cotrimoxazole
      and tetracycline 50% resistant to cephazolin gentamicin and kanamycin but 100%
      susceptible to chloramphenicol.

PMID- 8258474
TI  - Sudden blindness from pituitary apoplexy: a report of two cases.
AB  - Two cases of acidophil adenoma of the pituitary causing sudden blindness from
      pituitary apoplexy are presented. The tumours had been clinically silent, without
      producing any symptoms of endocrine dysfunction. Radiological evidence was very
      conclusive. Transfrontal craniotomy with decompression resulted in quick and
      dramatic visual improvement. The interesting syndrome of clinical manifestations
      is discussed.

PMID- 8258475
TI  - Preventive hematology.

PMID- 8258476
TI  - Trends in cancer incidence and mortality.
AB  - Time trends in cancer risk have often been summarised by the observation that
      mortality from cancers associated with tobacco is increasing rapidly, while
      mortality from all other cancers is either stable or falling slightly, this
      slight decline being dominated by the decrease in mortality from stomach cancer.
      Until recently, and with some variation between the sexes, this simple summary of
      cancer mortality trends would have been broadly correct for a number of developed
      countries, and it remains useful in dismissing claims of an impending and
      unexplained epidemic of cancer, but it does not apply to all countries, and in
      some there have recently been striking changes in the trends in mortality from
      cancers associated with tobacco. Cancer mortality has been widely accepted as the
      most important measure of progress against cancer, since it reflects the impact
      of cancer on people, and has been considered less subject to distortion than
      incidence or survival, although this is open to question. Cancer mortality also
      reflects trends in incidence and survival to a greater or lesser extent. There
      has been controversy, however, over how cancer mortality trends should be
      interpreted, as well as over which measures should be used to assess progress in
      cancer control. An overall summary of trends in mortality from all cancers
      combined is of limited value in assessing progress against cancer, in any case.
      Increases in a common lethal cancer may numerically dominate overall mortality
      trends, perhaps concealing declines in less common or less lethal cancers, while
      opposite trends in cancers of the lung and stomach, for example, might lead to an
      overall impression that little has changed. Further, up to a third of cancer
      patients will not die of cancer, and cancer mortality statistics do not reflect
      their experience at all. Cancer mortality trends only indirectly reflect trends
      in the number of people who are diagnosed with cancer in a given year, and those
      who do die of cancer in a given year may have been diagnosed more than 3 years
      previously, even though many die earlier: this blurs the responsiveness of
      routine cancer mortality statistics as a measure of recent progress, and
      alternative measures have been proposed. Trends in competing risks of death,
      especially at higher ages, may also complicate the interpretation of cancer
      mortality trends. The chance of developing cancer, and in that event, the chances
      of surviving it, are of direct interest to individuals.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8258477
TI  - Hearing disability in childhood--a cross-sectional and longitudinal investigation
      of causative factors.
AB  - This contribution describes and compares the causes of hearing disability in a
      cohort of children, born 1980-90, provided with hearing aids and included into
      the longitudinal surveillance programs of hearing-disabled children performed in
      two pediatric audiological units within the Copenhagen area. In addition the
      causes of hearing disability in childhood are compared with the causes found in a
      cohort born 1970-80, within the same geographical area, using the same criteria
      for hearing disability and diagnostic classification. No significant differences
      in the etiology of hearing disability were present in the two districts, and in
      the combined area prenatal causes accounted for 55% with inheritance (46%) being
      the most prominent cause of hearing disability. A significant increase in the
      incidence of inherited hearing disability among the prenatal causes from 69% in
      the 1970-80 cohort to 85% in the 1980-90 cohort was demonstrated, while a
      significant decrease in the incidence of foetal infection (i.e. rubella) from 27%
      to 9% within the two decades was demonstrated. No significant changes in the
      perinatal and postnatal causes were found from the 1970-80 to 1980-90 cohort, and
      although an improvement in the diagnostic procedures was found--i.e. a reduction
      from 26% to 20% in the incidence of unknown cause--the difference in the
      incidence of unknown cause is insignificant between the two decades. The
      investigation supports the need for continuous monitoring of the causes of
      hearing disability in childhood and supports the potential value of worldwide
      accepted criteria for etiological categories.

PMID- 8258478
TI  - Outpatient pediatric oesophagoscopy using a flexible fibreoptic bronchoscope.
      Design of an insufflation-aspiration adaptor.
AB  - The design of an adaptor for use with fibre-optic flexible endoscopes with a
      single instrument channel is described that enables them to be used for
      oesophagoscopy. The adaptor enables both aspiration of secretions as well as gas
      insufflation to expand the oesophagus distal to the tip of the endoscope down the
      single channel. When the adaptor is used on a pediatric bronchoscope it is
      possible to perform oesophagoscopy in an outpatient setting on the awake child.
      This application is particularly useful for the assessment of children who have
      ingested corrosive agents and enables rational management decisions to be based
      on precise knowledge of the extent of the mucosal injury.

PMID- 8258479
TI  - Detection of Haemophilus influenzae in middle ear of otitis media with effusion
      by polymerase chain reaction.
AB  - Otitis media with effusion (OME) is one of the major causes of hearing loss in
      childhood. The pathogenesis still remains unclear, though it is closely related
      to acute otitis media with bacterial infections. It is known that Haemophilus
      influenzae is one of the most common bacteria isolated from middle ear effusions
      (MEEs). Recently, in vitro DNA amplification by polymerase chain reaction (PCR)
      is a new technology that has considerable implication for diagnosis of viral and
      bacterial infections because of its potentially precise specificity and
      sensitivity. In the present experiment polymerase chain reaction (PCR) was
      applied to the detection of DNA genome of H. influenzae contained in middle ear
      effusions. By Southern blot hybridization, two characteristic bands for H.
      influenzae DNA were detected at 273 b.p. and 550 b.p. position in 15 of 27 MEEs.
      However, no organism was cultured by conventional methods. Our results indicate
      the PCR technique is more specific and sensitive in detection of bacteria in
      middle ear effusion of OME, compared with conventional methods. It strongly
      suggests more involvement of the bacteria, especially H. influenzae, in OME
      onset.

PMID- 8258480
TI  - Exposure to environmental tobacco smoke as a risk factor for recurrent acute
      otitis media in children under the age of five years.
AB  - Exposure to environmental tobacco smoke (ETS) has remained a controversial risk
      factor for otitis media in children. This study evaluates the association between
      exposure to ETS and recurrent acute otitis media (RAOM) in 85 cases and 85 age
      and gender matched controls under the age of 5 years. Cases and controls were
      obtained from outpatient otolaryngology and ophthalmology clinics, respectively,
      at the Children's Hospital of Eastern Ontario. Cases were defined as having four
      or more physician documented AOM episodes in the preceding 12 months and controls
      were otitis free in the prior 12 months. Exposure status was assessed via
      parental questionnaire. Controlling for other risk factors (via conditional
      logistic regression), such as daycare attendance, socioeconomic status,
      prematurity and family history of otitis media, a significant association between
      ETS and RAOM was evident (odds ratio = 2.68, 95% CI = 1.27-5.65). When
      categorized, a significant exposure response relationship between increasing
      level of exposure to ETS and increased risk of RAOM was evident. The population
      etiologic fraction indicated that up to 34% of RAOM cases may be accounted for by
      ETS exposure. We conclude that exposure to ETS is an important and modifiable
      risk factor for RAOM in children under the age of 5 years.

PMID- 8258481
TI  - Opsonization and phagocytosis of bacteria during various middle ear infections.
AB  - Samples of middle ear effusions (MEE) obtained from 50 children suffering from
      acute purulent otitis media (AOM; 23 ears), otitis media with effusion (OME; 15
      ears) or chronic suppurative otitis media (COM; 23 ears) were subjected to
      cytological (cellular differentiation, degree of phagocytosis) and
      bacteriological (species quantification and identification, degree of
      opsonization) analyses. Methods used were direct microscopy of acridine orange
      stained material, immunofluorescence assay using fluorescein-labelled antibodies
      to immunoglobulin G (IgG) and complement cleavage product C3b, and standard
      bacterial culturing on agar plates. The most intense opsonization and
      phagocytosis was evident in COM effusions culture-positive for Staphylococcus
      aureus. AOM and OME effusions showed rather poor opsonization and roughly 1% of
      the phagocytes harboured intracellular bacteria. COM effusions, culture-positive
      for Pseudomonas aeruginosa, showed no bacterial opsonization or phagocytosis
      whatsoever. Opsonization and phagocytosis of bacteria in the middle ear cleft is
      highly species-specific.

PMID- 8258482
TI  - Airway endoscopy in the diagnosis and treatment of bacterial tracheitis in
      children.
AB  - Children with bacterial tracheitis present with the symptoms of viral
      laryngotracheobronchitis or epiglottitis, but do not respond to appropriate
      therapy for these diseases and frequently develop acute respiratory
      decompensation. Since the treatment and outcome of bacterial tracheitis differ so
      much from those of viral laryngotracheobronchitis and epiglottitis, prompt and
      accurate diagnosis is essential. The aim of this study was to evaluate the
      significance of different diagnostic characteristics in a group of eleven
      patients and to compare the results to those recently reported in the pediatric
      and otorhinolaryngologic literature. The present study suggests that reliable
      predictive factors do not exist for bacterial tracheitis. No single clinical,
      radiological or laboratory feature was a reliable diagnostic predictor for
      bacterial tracheitis, nor was it any combination of these features. The only
      diagnostic procedure to distinguish bacterial tracheitis accurately and promptly
      from other forms of acute obstructive upper airway diseases was direct laryngo
      tracheo-bronchoscopy. Following endoscopic removal of all tracheal secretions and
      pulmonary toilet, nasotracheal intubation provides sufficient airway maintenance
      and obviates the need for tracheostomy. Endoscopy is thus diagnostic and
      therapeutic at the same time. If bacterial tracheitis is suspected a direct
      laryngoscopy and rigid tracheobronchoscopy should be performed under general
      anesthesia, as prompt diagnosis and adequate treatment are essential to survival.
      The cultures of the purulent tracheal secretions frequently revealed
      Staphylococcus aureus in combination with various pathogens, particularly the
      involvement of Pseudomonas aeruginosa was noted in two patients. Our data imply a
      susceptibility of children with Down's syndrome or immunodeficiency to bacterial
      tracheitis.

PMID- 8258483
TI  - Ectopic salivary gland tissue in the palatine and lingual tonsil.
AB  - A case is reported of a child born with a developmental field defect of the first
      branchial arch in whom there was partial obstruction of the oropharynx by a
      horseshoe-shaped mass of what was thought to be tonsillar tissue. 'Tonsillectomy'
      was performed but histopathological examination of the excised specimens showed
      them to be almost entirely made up of salivary gland tissue.

PMID- 8258484
TI  - Medium term fate of cartilage grafts from children after laryngo-tracheoplasty.
AB  - Cartilage grafts or biopsies of such grafts were obtained from six children who
      had undergone laryngo-tracheoplasty surgery at times ranging from 10 to 38 months
      after surgery. The histological appearance of the grafted cartilage was of
      gradual degeneration with chondrocyte necrosis and replacement of cartilage
      matrix by fibrous tissue.

PMID- 8258485
TI  - Tracheoesophageal fistula: a case report.
AB  - Tracheoesophageal fistula without atresia (H-type) is a known but uncommon cause
      of respiratory distress in the newborn. We present a rare case of a high cervical
      tracheoesophageal fistula unassociated with a laryngeal cleft or esophageal
      atresia. The diagnosis, associated anomalies, and surgical repair of this
      previously undescribed entity are discussed.

PMID- 8258486
TI  - Myxoma of the mandible.
AB  - Myxoma is a rare bone tumor of the jaws. The exact aetiology and pathogenesis of
      this tumor still remains obscure. The tumor is frequently seen in young adults
      and in the mandible. Enucleation or local curetting have been recommended in the
      literature as the treatments of choice, although some authors have suggested more
      radical procedures because of the recurrences. In this paper a case of myxoma of
      the mandible and a review of the literature is presented.

PMID- 8258487
TI  - Acinic cell carcinoma of the parotid gland in childhood.
AB  - A 13-year-old girl underwent surgery at the Ear Nose and Throat Department of the
      Children's Hospital and Scientific Research Institute, Bambino Gesu, Rome,
      because of an acinic cell carcinoma of the parotid gland. Two years after total
      parotidectomy with preservation of the facial nerve, metastasis occurred in a
      lateral cervical lymph node. Acinic cell tumors are uncommon in childhood; in
      children under the age of 16 years only 35 cases have been reported. There are
      too few acinar cell carcinomas occurring in children to yield an idea of their
      natural course. The neoplasm is also referred to as 'acinar cell tumor', in
      contrast to acinar cell carcinoma, because the neoplasm may be benign or
      malignant. Unfortunately, there are no histological distinguishing features that
      permit the pathologist to determine which neoplasm will behave in an aggressive
      fashion.

PMID- 8258488
TI  - Fatal gas embolism as a complication of Nd-YAG laser surgery during treatment of
      bilateral choanal stenosis.
AB  - A 40-day-old infant boy underwent Nd-YAG laser surgery because of congenital
      bilateral choanal stenosis. Cyanosis and cardiovascular collapse occurred during
      the operation. Resuscitation was initiated, but in vain; the patient died. The
      evolution of clinical events was consistent with a diagnosis of gas embolism. In
      the investigation of causes, the use of a sapphire tip with the Nd-YAG laser and
      the cooling of the tip with N2 gas were thought to have contributed to the fatal
      outcome. The authors warn of the potential risk of gas embolism with the Nd-YAG
      laser and a coaxial gas cooling system, and they emphasize the importance of
      monitoring for gas embolism in high-risk patients.

PMID- 8258489
TI  - Early identification of hearing impairment in infants and young children. NIH
      Consensus Development Conference.

PMID- 8258490
TI  - Nonsteroidal anti-inflammatory drugs in ophthalmology.

PMID- 8258491
TI  - Intraocular irrigating solutions: the importance of Ca++ and glass versus
      polypropylene bottles.

PMID- 8258492
TI  - Viscoelastics.

PMID- 8258493
TI  - Corneal wound healing and fibronectin.

PMID- 8258494
TI  - Antifibrotic agents in glaucoma filtering surgery.

PMID- 8258495
TI  - Pharmacology of botulinum toxin.

PMID- 8258496
TI  - Clinical use of cyclosporine in ocular disease.

PMID- 8258497
TI  - Pharmacological treatment of ocular allergic diseases.

PMID- 8258498
TI  - The fluoroquinolones: new antibiotics in ophthalmology.

PMID- 8258499
TI  - Ocular antivirals.

PMID- 8258500
TI  - Prolonged-action drops.

PMID- 8258501
TI  - Steroids.

PMID- 8258502
TI  - Collagen shields.

PMID- 8258503
TI  - Concanavalin A-induced posterior subcapsular cataract: a new model of
      cataractogenesis.
AB  - PURPOSE: To evaluate the effect of Concanavalin A (Con A) on cataract formation
      in New Zealand Albino rabbits. Uveitis is a chronic inflammatory condition of the
      eye involving the anterior and/or posterior segments. It may be acute or chronic
      and is associated with the development of posterior subscapular cataract over
      time. Con A is a nonspecific inflammatory agent and mitogen for T cells and some
      B cells. Used extensively in immunogenic studies Con A has been shown to induce
      uveitis after intravitreal injection in New Zealand Albino rabbits. METHODS: In
      two separate studies, Con A was injected intracamerally or intravitreally into
      one eye of 12 New Zealand Albino rabbits and an equal volume of balanced salt
      solution was injected into the opposite eye as a control. In a third study, the
      effect of topical steroids after intravitreal injection of Con A was evaluated.
      In all studies, anterior and posterior inflammation and the development of
      cataract was monitored by slit lamp biomicroscopy and photography. Cataract
      formation was also studied histopathologically. RESULTS: Initially, all eyes
      treated with Con A demonstrated moderate anterior chamber inflammation while eyes
      treated with balanced salt solution showed no inflammation. Three months after
      treatment, posterior subcapsular cataracts were present in all rabbit eyes
      treated with intravitreal Con A. In the third study, topical steroid treatment of
      Con A-induced inflammation significantly reduced anterior chamber inflammation
      but had no effect on vitreous humor and posterior subcapsular cataract formation.
      CONCLUSION: This experimental model was the first to demonstrate the development
      of posterior subcapsular cataracts after Con-A induced inflammation. The cataract
      was clinically and histologically similar to human posterior subscapular
      cataracts.

PMID- 8258504
TI  - Morphologic characteristics and chemical composition of Christmas tree cataract.
AB  - PURPOSE: Christmas tree cataract consists of highly refractile multicolored
      "needles" crisscrossing the lens fibers of the deep cortex. The fact that the
      colors vary according to the angle of the incident light, and that in
      retroillumination only a dim outline of the cataract is seen, would suggest that
      Christmas tree cataract is a diffractive phenomenon. This study was performed to
      unravel the ultrastructure and chemical composition of the Christmas tree
      needles. METHODS: Eight lenses from donor eyes and four extracapsularly extracted
      lenses with Christmas tree cataract were investigated by scanning and
      transmission electron microscopy. The chemical composition was studied with
      energy-dispersive x-ray microanalysis and Raman microspectroscopy. RESULTS:
      Scanning electron microscope examination showed that the needles are smooth,
      rectangular, plate-like elements bordered by membranes and amorphous material and
      running crisscross through the lens. In the specimens for transmission electron
      microscopic examination, the needles proved to be largely dissolved, but the
      remains showed regular spacings of approximately 5 nm. Material identical in
      spacing and electron density was found in neighboring cells bound to a reticular
      membranous network originating from the fiber-limiting membranes. Energy
      dispersive x-ray and Raman microanalysis showed that the needles have a high
      sulfur content and pronounced S-S, CS-SC, and C-S vibrations. The cytoplasm
      adjacent to the needles and reticular meshwork had an elevated Ca++ content.
      CONCLUSIONS: It is concluded that cystine is the most likely candidate for the
      Christmas tree needles and that the needles probably are formed as the result of
      an age-related aberrant breakdown of crystallins induced by elevated Ca++ levels.

PMID- 8258505
TI  - Posterior subcapsular cataract in endogenous Cushing syndrome: an uncommon
      manifestation.
AB  - PURPOSE: Posterior subcapsular cataract is a well-known complication of
      longstanding glucocorticoid therapy (exogenous Cushing syndrome). The purpose of
      this study was to examine the effect of chronic endogenous hypercortisolism
      (endogenous Cushing syndrome) on the human lens. METHODS: Sixty consecutive
      patients (8 to 67 years of age, 46 females, 14 males) with endogenous Cushing
      syndrome were studied. The exposure to cortisol was estimated based on the
      duration of the disease and measurements of the 24-hour urine free cortisol
      excretion. Complete ocular examination included biomicroscopy of the lens after
      dilation. RESULTS: Duration from the onset of endogenous Cushing syndrome ranged
      from 1 to 20 years (mean +/- SD, 5.5 +/- 3.7). Urine free cortisol excretion
      ranged from 250 to 3065 micrograms/24 hr (mean +/- SD, 693 +/- 547; normal
      values, 20 to 90 micrograms/24 hr). Only two of the 60 patients (3.3%) had
      posterior subcapsular cataract. This low prevalence contrasts to the high
      prevalence attributed to glucocorticoid therapy with grossly equivalent total
      dosage of glucocorticoids. CONCLUSION: It was concluded that posterior
      subcapsular cataract is an infrequent complication of endogenous hypercortisolism
      compared to exogenous Cushing syndrome. Because the total exposure to endogenous
      glucocorticoids was not lower than that of exogenous glucocorticoid therapy, a
      potential explanation for this difference might be the exposure of the lens to
      the natural (cortisol) rather than a synthetic glucocorticoid or pharmacokinetic
      differences of glucocorticoids between the two forms of Cushing syndrome.

PMID- 8258506
TI  - Sensitivity in the nasal and temporal hemifields in children treated for
      cataract.
AB  - PURPOSE: To determine if form-deprived aphakes, like normal infants, show
      especially poor sensitivity in the nasal visual field. The purpose of this
      article was also to examine the influence on their peripheral sensitivity of the
      timing and duration of deprivation, of whether deprivation was monocular or
      binocular, and of having patched the fellow nondeprived eye. METHODS: Static
      perimetry was used to measure intensity thresholds at 20 degrees in the nasal
      visual field and at 30 degrees in the temporal visual field in normal subjects (n
      = 20 7-year-old children, 20 8-year-old children, 12 9-year-old children, and 20
      adults) and in 46 children treated for a dense and central cataract in one (n =
      21) or both (n = 25) eyes. The deprivation began either at birth or after a
      normal early history, and the duration of deprivation varied widely among
      patients. Also tested were two adults who had been treated promptly for
      unilateral cataracts that had developed after the age of 40 years. RESULTS: In
      normal subjects, sensitivity was slightly higher at 20 degrees nasally than at 30
      degrees temporally, with no developmental changes in sensitivity at either
      location. The deprived eyes of the children had losses in sensitivity at both
      locations but only children treated for unilateral congenital cataract had larger
      losses at 20 degrees nasally than at 30 degrees temporally. There were no
      significant effects on their sensitivity of the duration of deprivation or, in
      children treated for unilateral cataract, of patching of the nondeprived eye. In
      contrast, the two patients in whom cataracts did not develop until adulthood had
      normal sensitivity. CONCLUSIONS: Pattern deprivation interferes with the
      development of peripheral sensitivity at both 30 degrees temporally and 20
      degrees nasally. Nasal sensitivity, which is slow to mature, is affected more by
      early monocular deprivation than by early binocular deprivation. The results are
      consistent with the hypothesis that unfair interocular competition during early
      infancy especially affects visual functions that are slow to mature.

PMID- 8258507
TI  - The phenol red thread tear test: a cross-cultural study.
AB  - PURPOSE: To examine the results of the phenol red thread tear test in a cross
      cultural comparison. METHODS: Two groups of 500 controlled normal subjects who do
      not wear contact lenses from the United States and Japan were investigated.
      RESULTS: The mean wet length of the thread for the United States was 23.9 mm (SD
      9.5 mm). The mean for Japan was 18.8 mm (SD 8.6 mm). There was a significant
      difference between the two countries (P < 0.05). Males subjects had significantly
      longer wet lengths than females for both countries (P < 0.05). There was a
      moderate correlation between right and left eye results for both countries.
      CONCLUSIONS: The phenol red thread tear test was found to be easy to administer.
      Results were in line with current knowledge and theories of the lacrimal system.
      Results also indicated that this test may disclose subtle differences not
      previously found with other tear tests.

PMID- 8258508
TI  - Role of wax ester fatty alcohols in chronic blepharitis.
AB  - PURPOSE: This study was performed to determine the difference in the composition
      of wax ester fatty alcohols from meibomian gland secretions from normal people
      and those with blepharitis, and to determine which lipids are associated
      significantly with specific chronic blepharitis disease groups. METHODS: Fatty
      alcohols, isolated by thin-layer chromatography from the wax and sterol ester
      fraction of human meibum, were analyzed by gas chromatography-mass spectroscopy
      after oxidative ozonolysis and silylation of the alcohol groups. Relative amounts
      of individual lipids or lipid groupings in each patient group were analyzed
      statistically by Dunnett's comparison, with the overall significance level
      adjusted for multiple testing (Bonferroni adjustment). RESULTS: Significant
      differences (P < 0.05) between the normal group and five disease groups were
      found in certain alcohol groups. These alcohols included certain normal (straight
      chain-methyl group on chain end) and anteiso (methyl group on second carbon from
      chain end) alcohols, as well as the ratio of iso (methyl group on first carbon
      from chain end) to anteiso alcohols. The results also suggested that alpha
      oxidation activity was significantly different for certain groups. The
      unsaturated alcohols were primarily normal alcohols. Epoxy-fatty acids also were
      present in the alcohol fraction. CONCLUSIONS: These data suggest that meibomian
      gland lipid differences may contribute significantly to some chronic blepharitis
      disease signs and also suggest that peroxisomal or endoplasmic reticulum
      abnormalities may contribute in part to some of these lipid differences.

PMID- 8258509
TI  - Serum levels of tumor necrosis factor-alpha and interleukin-6 in ocular
      cicatricial pemphigoid.
AB  - PURPOSE: These studies examined regulation of the cytokines interleukin-6 and
      tumor necrosis factor-alpha in ocular cicatricial pemphigoid (OCP), a systemic
      autoimmune disease. METHODS: Serum levels of interleukin-6 and tumor necrosis
      factor-alpha in sera collected from 35 patients with OCP, 29 normal persons and
      17 patients with ocular inflammatory diseases were determined using an enzyme
      linked immunosorbent assay. RESULTS: Levels of interleukin-6 were significantly
      decreased in sera of patients with OCP (median, 28.9; range, 7.5 to 136.7 pg/ml,
      P < 0.001) compared with sera from normal subjects (median, 65.2; range, 21.1 to
      303.9 pg/ml). Sera from patients with non-OCP, extraocular inflammatory diseases
      and uveitis, showed no such decrease. In contrast, tumor necrosis factor-alpha
      levels were significantly elevated in OCP patients (median, 22.5; range, 8.3 to
      44.4 pg/ml, P < 0.001), whereas no such increase was observed in sera from
      patients with extraocular inflammatory disease or uveitis, compared to normal
      sera controls (median, 17.4; range, 5 to 27.2 pg/ml). CONCLUSIONS: These results
      suggest that elevated serum tumor necrosis factor-alpha levels and decreased
      serum interleukin-6 levels can be added to the increasing list of systemic
      immunologic correlates of active OCP, again emphasizing that OCP is a systemic
      disease whose primary manifestation is ocular.

PMID- 8258510
TI  - Motion perception in glaucoma.
AB  - PURPOSE: This study was performed to investigate motion perception in patients
      with glaucoma. METHODS: A random dot motion test was used to measure three
      aspects of central motion perception: minimum displacement threshold (Dmin),
      maximum displacement threshold (Dmax), and coherence threshold (signal to noise).
      Motion perception was assessed in 15 patients with primary open-angle glaucoma,
      23 low-risk patients in whom glaucoma was suspected, and 24 age-matched normal
      subjects. RESULTS: Central motion perception was significantly impaired in
      patients with glaucoma; in particular, the Dmin was nearly twice that for the
      normal subjects (glaucoma mean, -0.27 +/- 0.24 log minutes of arc; normal mean, 
      0.56 +/- 0.13 log minutes of arc; F = 21.79, P < 0.001). Furthermore, Dmin values
      fell outside the normal range in 10 of the 15 patients with glaucoma, despite
      normal visual acuity and normal foveal perimetric thresholds. Coherence
      thresholds and Dmax did not discriminate between patients with glaucoma and
      normal subjects. Dmin was not correlated with any indices of perimetric
      sensitivity, and none of the tests of motion perception showed any abnormalities
      in patients in whom glaucoma was suspected. CONCLUSIONS: Central motion
      perception can be affected in glaucoma and may reflect preferential damage to
      larger retinal ganglion cells. Future work will measure Dmin in a larger
      population of patients with suspected glaucoma and those with glaucoma, and
      investigate peripheral motion perception in glaucoma.

PMID- 8258511
TI  - Characteristics of frequency-of-seeing curves in normal subjects, patients with
      suspected glaucoma, and patients with glaucoma.
AB  - PURPOSE: The authors performed this study to determine factors that affect the
      characteristics of frequency-of-seeing curves in normal subjects, patients with
      suspected glaucoma, and patients with glaucoma. METHODS: The sample consisted of
      70 subjects (22 normal subjects, 12 patients with suspected glaucoma, and 36
      patients with glaucoma). A program was written to interface with the Humphrey
      Field Analyzer (Humphrey Instruments, San Leandro, CA) to measure frequency-of
      seeing curves. The authors presented stimuli 8 dB either side of the estimated
      threshold in 1-dB intervals with five repetitions at each stimulus intensity. The
      authors tested four to six locations in each subject, with randomization of the
      stimulus intensity and location. Fixation was monitored with the Heijl-Krakau
      method. Using a probit program, the authors calculated the threshold and slope
      (estimated by the interquartile range) of each curve. RESULTS: The authors
      obtained 124 curves from the normal subjects, 71 from the patients with suspected
      glaucoma, and 183 from the patients with glaucoma. In all three groups, the slope
      of the frequency-of-seeing curve was correlated highly with the threshold or
      threshold deviation, although the correlation was significantly higher in the
      normal subjects compared with the patients with suspected glaucoma and patients
      with glaucoma, even after controlling for the range of the threshold and
      threshold deviation. For this reason, the authors found considerably different
      frequency-of-seeing curves, between subject groups and also within the group of
      patients with glaucoma, in locations with the same threshold. CONCLUSIONS: There
      may be fundamental differences in areas of normal subjects and patients with
      glaucoma with similar thresholds or threshold deviations. These differences also
      may exist within patients with glaucoma.

PMID- 8258512
TI  - Serum proteins and aqueous outflow resistance in bovine eyes.
AB  - PURPOSE: Recent evidence shows that much of the protein in the anterior chamber
      aqueous humor enters diffusively through the root of the iris. The proximity of
      the protein entry point to the trabecular meshwork suggests that the protein
      content of the aqueous humor in the trabecular meshwork might be much higher than
      previously suggested. The authors were interested in investigating the possible
      hydrodynamic implications of these proteins. METHODS: Bovine eyes were perfused
      with concentrations of bovine serum in buffer ranging from 0% to 15% to determine
      the effect on outflow resistance. Immunohistochemical methods were used on these
      eyes and unperfused eyes to determine the distribution of albumin in the anterior
      segment. RESULTS: Preliminary perfusion studies suggested that increasing the
      concentration of serum in buffer from 0% to 15% decreased the rate of "wash-out"
      in bovine eyes, with a 15% solution essentially eliminating the wash-out
      phenomenon. Perfusion of a series of bovine eyes with a total of 5 ml of 15%
      serum in buffer showed a "wash-out" rate of 0.0498 +/- 0.0428
      ([microliters/min/mm Hg]/[ml perfusate]), whereas control eyes perfused with
      buffer washed-out at a rate of 0.1677 +/- 0.0271 (P < 0.05); a second series of
      eyes perfused with a total of 10 ml of 15% serum washed-out at a rate of 0.0533
      +/- 0.0294, whereas control eyes had a rate of 0.1813 +/- 0.0342 (P < 0.02).
      Immunohistochemical investigations showed significant quantities of albumin in
      the outflow pathway of unperfused eyes, whereas perfusion with buffer eliminated
      this protein; perfusion with 10% to 15% serum in buffer maintained the level of
      albumin in the outflow pathway similar to that found in unperfused eyes. Use of
      cuprolinic blue in a critical electrolyte concentration confirmed previous
      findings that sulfated proteoglycans are not eliminated from the trabecular
      meshwork during wash-out. CONCLUSIONS: Wash-out in nonhuman species may result
      from progressive depletion of an anterior segment depot of plasma-derived
      proteins entering the trabecular meshwork. Modeling studies confirm that plasma
      derived proteins in the aqueous humor of the trabecular meshwork can generate a
      significant fraction of aqueous outflow resistance. The lack of wash-out in human
      eyes suggests that this system may maintain flow resistance in a fashion
      fundamentally different from other species.

PMID- 8258513
TI  - Posttranslational phosphorylation of lens fiber connexin46: a slow occurrence.
AB  - PURPOSE: To study in both in situ and primary cultures the posttranslational
      phosphorylation of connexin46 (Cx46), one of two members of the connexin family
      of gap junction proteins expressed by lens fibers. METHODS: Phosphatase
      digestion, gel electrophoresis, cell culture, organ culture, immunoprecipitation,
      metabolic labeling, and phosphoamino acid analysis were the methods used in this
      study. RESULTS: Cx46 immunoprecipitated from either rat or bovine lenses resulted
      in a shift to a more rapidly migrating species. During rat embryonic development,
      the more rapidly migrating, nonphosphorylated form of Cx46 was prevalent at 15
      days gestation; as development progressed, there was a loss of the
      nonphosphorylated form with a concomitant increase in the phosphorylated form,
      such that by 28 days after birth only the phosphorylated form was detectable. The
      rate of posttranslational phosphorylation was very slow compared to previously
      measured rates for connexin43. Primary cultures of rat embryonic lens epithelial
      cells, which contained differentiating lentoids, were labeled with 35S-methionine
      and chased for 8 days. Very low levels of Cx46 were detectable, and none of this
      labeled material shifted to the slower mobility during the 8-day chase period.
      Similarly, in organ culture of bovine lenses, Cx46 could be labeled with 35S
      methionine, but the immunoprecipitated material remained in the rapidly migrating
      form for 1 week, the longest time measured. This immunoprecipitated material was
      shown to be serine-phosphorylated, which was insufficient to cause the
      electrophoretic mobility shift. CONCLUSIONS: There are low levels of Cx46
      synthesis and phosphorylation in rat embryo lens primary cultures and a slow rate
      of phosphorylation of Cx46 in bovine organ cultures.

PMID- 8258514
TI  - Quantal and visual efficiency of fluorescence in the lens of the human eye.
AB  - PURPOSE: To document quantitatively the fluorescence in the human lens relevant
      to its interference with visual function. To explain quantitatively the
      experimental findings relative to loss of visual function. To study the relation
      between the fluorescence and the light transmission of the lens. METHODS: Three
      normal lenses, from 22-, 28-, and 69-year-old donors, were used. Fluorescent
      light was induced by a 4-mm diameter pencil beam of 380, 400, or 420 nm. It was
      measured as a function of the deflection angle from -10 to 150 degrees for
      different wavelengths. RESULTS: The shapes of the emission spectra were
      comparable to those reported in the literature. Total quantal efficiency of
      fluorescence was between 5% for 69 years and 380 nm excitation and 0.4% for 22
      years and 420 nm excitation. The forward intensity was less than the backward
      intensity because of secondary absorption. CONCLUSIONS: Fluorescence of the lens
      causes light with wavelengths of 420 nm and lower to be much more visually
      effective. A marked homogeneous veil is added to the point spread function. The
      total increase in luminous efficiency was a factor 3 to 6 at 400 nm, and a factor
      70 to 150 at 380 nm. For other visual effects (glare) the increase can be larger.

PMID- 8258515
TI  - Apolipoprotein A-I and B distribution in the human cornea.
AB  - PURPOSE: To determine the presence and localization of apolipoprotein A-I, a
      marker for high density lipoprotein, and apolipoprotein B, a marker for low
      density lipoprotein, in human cornea; to examine the relationship of these
      lipoprotein markers with areas of lipid accumulation in the cornea. METHODS: A-I
      and B apolipoproteins were localized in frozen sections of human corneas with
      specific monoclonal antibodies using avidin-biotin immunoperoxidase labelling.
      Corneal lipid was colocalized with apolipoproteins by oil red 0 staining of
      immunostained sections. RESULTS: Staining data showed that apolipoprotein B and
      lipid accumulated in the extracellular spaces of peripheral corneal stroma.
      However, their distributions were not coincident. The posterior region of
      peripheral corneal stroma (including Descemet's membrane) often contained lipid
      without immunodetectable apolipoprotein B. Unexpectedly, apolipoprotein A-I was
      associated with many keratocytes throughout the cornea in addition to an
      extracellular distribution heaviest in peripheral cornea. CONCLUSIONS: Lipid
      deposits lacking apolipoprotein B in peripheral cornea suggest that if
      accumulated corneal arcus lipid is derived from extracellular deposition of
      plasma low density lipoprotein, the low density lipoprotein is altered such that
      it looses its immunoreactive apolipoprotein B. The unexpected association of
      apolipoprotein A-I with keratocytes suggests that these cells are either taking
      up or synthesizing a protein sharing an immunoreactive epitope with
      apolipoprotein A-I.

PMID- 8258516
TI  - Alternatively spliced fibronectin molecules in the wounded cornea: analysis by
      PCR.
AB  - PURPOSE: To determine whether certain fibronectin isoforms participate in corneal
      epithelial wound healing, the authors used the polymerase chain reaction to
      detect different splicing patterns of the EIIIA segment of fibronectin mRNA in
      epithelial scrape-wounded cornea of rats. METHODS: Specific fibronectin cDNA
      sequences synthesized from rat cornea with total RNA were amplified with various
      sets of synthetic oligonucleotide primers. RESULTS: The authors detected both the
      EIIIA+ and EIIIA- fibronectin mRNA isoforms during corneal wound healing. The
      kinetics of corneal expression of both total fibronectin mRNA and the EIIIA-
      fibronectin mRNA isoform was polyphasic; an initial decrease was followed by an
      increase at 45 minutes, a second increase at 2 hours, and a third increase at 4
      days after wounding. EIIIA+ fibronectin mRNA, not found in normal cornea, also
      was detected during healing. CONCLUSIONS: The expression of total fibronectin
      mRNA and both the EIIIA+ and EIIIA- fibronectin mRNA is upregulated during
      corneal epithelial wound healing. The expression of EIIIA+ fibronectin mRNA
      during wound healing, a fibronectin isoform that was highly expressed in
      embryonic tissue, suggests that this fibronectin isoform is involved functionally
      in corneal wound healing.

PMID- 8258517
TI  - Continuous epidermal growth factor delivery in corneal epithelial wound healing.
AB  - PURPOSE: To investigate the effects of a single prolonged exposure to recombinant
      epidermal growth factor on the healing of anterior keratotomy wounds in New
      Zealand white rabbits. METHODS: After wounding, eyes were perfused for 1, 2, 4,
      and 8 hours with either epidermal growth factor solution at a concentration of 50
      micrograms/ml or balanced saline solution using a Morgan therapeutic lens (Mortan
      Inc, Missoula MT) and a syringe pump. Furthermore, concentration response was
      evaluated by perfusing with epidermal growth factor solutions at concentrations
      of 5, 50, 100 and 500 micrograms/ml for 4 hours. Wound healing rates were
      determined by quantitative morphometry of the wound area. The ratio of healing
      rates of eyes perfused with epidermal growth factor and control eyes provided a
      measure of the effect of epidermal growth factor on wound healing, and was
      defined as the epidermal growth factor enhancement factor. RESULTS: The
      enhancement factor was found to be 1.04 +/- 0.08, 1.17 +/- 0.07, 1.43 +/- 0.09,
      and 1.59 +/- 0.07 for perfusion times of 1, 2, 4, and 8 hours, respectively. The
      concentration response enhancement factors were 0.99 +/- 0.08, 1.43 +/- 0.09,
      1.21 +/- 0.09, and 0.95 +/- 0.07 for the 5, 50, 100, and 500 micrograms/ml 4-hour
      perfusions, respectively. CONCLUSION: The results indicated that continuous
      epidermal growth factor exposures of as few as 2 hours produced a significant
      increase in healing rates (P < 0.05); increasing the time of exposure further
      increases the rate of wound healing. Results from the concentration response
      experiments showed that the optimum epidermal growth factor concentration for
      enhancing epithelial wound healing is approximately 50 micrograms/ml.

PMID- 8258518
TI  - Thrombospondin and in vivo angiogenesis induced by basic fibroblast growth factor
      or lipopolysaccharide.
AB  - PURPOSE: To reexamine the possible effect of human thrombospondin on in vivo
      angiogenesis. METHODS: In vivo angiogenesis in the rabbit cornea was induced by
      implants of Elvax-40 sequestering human recombinant basic fibroblast growth
      factor (bFGF) or bacterial endotoxin lipopolysaccharide (LPS). Implants
      sequestering various concentrations of thrombospondin were examined for their
      ability to induce angiogenesis and also for their possible influence on the
      angiogenic potential of bFGF- or LPS-sequestering implants. RESULTS: Constant and
      reproducible angiogenic stimuli were obtained with implants sequestering 250 ng
      or more of bFGF or 100 ng or more of LPS. Implants sequestering 500 ng of
      thrombospondin induce very little clinical change but larger concentrations
      induce infiltration of leukocytes and a mild angiogenic stimulus. Combination of
      thrombospondin implants with bFGF or LPS implants enhanced the angiogenic
      response to either of these factors. The thrombospondin enhancing effect was more
      prominent when LPS was the stimulating factor. Histologic examination of the
      tested corneas disclosed that the LPS angiogenic stimulus follows the influx of
      leukocytes. Conversely, the bFGF angiogenic stimulus appears to be associated
      with the proliferation of stromal keratocytes and corneal epithelial cells. The
      thrombospondin angiogenic enhancing effect on both the LPS and bFGF stimuli was
      correlated with an increased infiltration of polymorphonuclear cells. CONCLUSION:
      In this system, thrombospondin enhanced the in vivo angiogenic process induced by
      bFGF or LPS. This enhancement appears to be associated with an in vivo activation
      and chemotactic effect on the polymorphonuclear cells.

PMID- 8258519
TI  - Effect of aging on retinal macular microcirculation: a blue field simulation
      study.
AB  - PURPOSE: Structural changes in the retina are known to occur with aging. This
      study was performed to investigate whether aging also affects the retinal macular
      microcirculation. METHODS: Healthy volunteers with ages ranging from 20 to 78
      years (mean +/- SD, 49 +/- 19 years) were included in this study. The retinal
      macular microcirculation was assessed with the blue field simulation technique,
      based on the blue field entoptic phenomenon. Subjects were asked to match the
      velocity and density of computer-simulated particles displayed on a screen with
      those of their entoptically observed leukocytes. Ten matching trials were
      performed, and an average leukocyte velocity and density were calculated.
      RESULTS: Significant negative linear correlations were observed between velocity
      and age (P = 0.0001) and density and age (P = 0.009). Older subjects (50 to 78
      years of age) had a significantly slower velocity (0.61 +/- 0.21 mm/s) and
      smaller density (90 +/- 43 particles per field of view) than younger subjects
      (0.92 +/- 0.12 mm/s and 135 +/- 65 particles, respectively; unpaired Student's t
      test, P = 0.001 and P = 0.01, respectively). CONCLUSIONS: These results suggest
      that, in normal subjects, retinal macular blood flow decreases with age. The 20%
      decrease in average velocity with age is very similar to the age-related decrease
      in number of cells observed in the human foveal ganglion cell layer.

PMID- 8258520
TI  - Endothelium-dependent regulation of the ophthalmic microcirculation in the
      perfused porcine eye: role of nitric oxide and endothelins.
AB  - PURPOSE: The endothelium produces nitric oxide and endothelin (ET). This study
      was designed to investigate the endothelium-dependent regulation of the porcine
      ophthalmic microcirculation. METHODS: Isolated porcine eyes were perfused with a
      modified Langendorff setup (Hugo Sachs Elektronik KG, Freiburg, Germany) at a
      perfusion pressure of 80 cm H2O with Krebs-Ringer bicarbonate solution (37
      degrees C; 95% O2, 5% CO2). RESULTS: The inhibitor of nitric oxide formation, L
      nitroarginine methylester (L-NAME; 10(-6) to 10(-4) M), evoked decreases in flow
      (maximal decrease, 39% +/- 6%; P < 0.005 versus control). The endothelium
      dependent vasodilator bradykinin evoked increases in ophthalmic flow (maximal
      increase, 26% +/- 2%; P < 0.05 versus control) prevented by L-NAME. The effect of
      endothelin-1 (ET-1; 10(-12) to 10(-11) M) on flow was biphasic, with early
      vasodilation (1 to 2 minutes) and late vasoconstriction. At 10(-12) M, the
      increase in flow was most pronounced (24% +/- 5%; P < 0.05 versus control),
      whereas 10(-10) M caused only significant decreases in flow (59% +/- 5%; P <
      0.001 versus control). Endothelin-3 (ET-3) evoked similar vasodilator effects as
      ET-1 but less vasoconstriction. The vasodilator effects of ET-3 were prevented by
      pretreatment of the eye with indomethacin (10(-5) M, to block the production of
      prostaglandins; P < 0.05 versus control). The endothelinA receptor antagonist FR
      139317 significantly reduced vasoconstriction to ET-1 (10(-10) M; P < 0.001
      versus control). The thromboxane analogue (U-46619) reduced flow in a
      concentration-dependent manner (P < 0.001 versus control). CONCLUSIONS:
      Endothelium-derived nitric oxide released under basal conditions or stimulated by
      bradykinin significantly regulated flow to the porcine ophthalmic
      microcirculation. This vasodilator system may play an important protective role
      against vasospasm. In contrast, ET-1 has vasodilator effects through the release
      of prostaglandins and potent vasoconstrictor properties mediated through ETA
      receptors.

PMID- 8258521
TI  - Complete elimination ('cure') of progressively growing intraocular tumors by
      local injection of tumor-specific CD8+ T lymphocytes.
AB  - PURPOSE: The purpose of this study was to examine if anterior chamber tumors
      could be eliminated by adoptive immunotherapy. METHODS: Precursor T cells were
      recovered from lymph nodes draining subconjunctival space or anterior chamber
      tumors and restimulated in vitro to obtain fully functional tumor-specific CD8+
      cytolytic T cells. RESULTS: Subconjunctival space tumor-derived cytolytic T cells
      eliminated tumors completely when injected simultaneously into the eye with the
      tumor cells, or when the anterior chamber injection was delayed for up to 3 days.
      In vitro restimulated cytolytic T cells obtained from lymph nodes draining
      progressively growing anterior chamber tumors were as effective as those obtained
      from lymph nodes draining subconjunctival space tumors, indicating that mice with
      anterior chamber tumors possess precursor cytotoxic T cells with the potential to
      differentiate into cytolytic T cells capable of eliminating intraocular tumors.
      By determining the frequency of tumor-specific cytolytic T cells in the effector
      cell inocula, it was estimated that cures of intraocular tumors are possible when
      the ratio of cytolytic T cells to tumor cells is less than 1:50, and the total
      tumor burden at the time of adoptive immunotherapy is less than 80,000 viable
      tumor cells. CONCLUSIONS: It was concluded that terminally differentiated,
      antigen-specific, cytotoxic T cells injected directly into an intraocular tumor
      site are capable of eliminating the tumor, and may represent a mode of ocular
      tumor immunotherapy in the future.

PMID- 8258522
TI  - Integrin expression in uveal melanoma differs from cutaneous melanoma.
AB  - PURPOSE: During the process of metastasis, changes in cell-cell and cell-matrix
      contacts occur; therefore, expression of integrins, a superfamily of adhesion
      molecules, may be important. Expression of integrins has been studied extensively
      in cutaneous melanoma. Because it is known that uveal melanoma has a metastatic
      behavior different from cutaneous melanoma, the authors investigated integrin
      expression in uveal melanoma. METHODS: The authors used monoclonal antibodies
      recognizing integrin subunits alpha 1-6, alpha v, beta 1, and beta 4 and
      integrins alpha v beta 3 and alpha v beta 5 on frozen sections of 32 human
      primary uveal melanomas and 4 metastases, followed by an avidin-biotin-peroxidase
      complex-immunoperoxidase technique. RESULTS: As in cutaneous melanoma, alpha 4
      expression was rare, but most lesions expressed alpha 3 and alpha 6. In contrast
      to cutaneous melanoma, in which alpha 2 is well expressed in most lesions and
      alpha 5 is expressed only in a small percentage of lesions, alpha 2 expression
      was rare in uveal melanoma and alpha 5 expression was found in all lesions. A
      major difference was observed with regard to the alpha v beta 3 vitronectin
      receptor. In contrast to cutaneous melanoma, in which alpha v beta 3 is expressed
      in advanced primary melanomas and metastases, alpha v beta 3 was not detected in
      any of the primary uveal melanomas, but all lesions strongly expressed alpha v
      beta 5. CONCLUSIONS: Integrin expression in uveal melanoma cannot be correlated
      with cell type or invasiveness. In contrast to cutaneous melanoma, it seems that
      determination of the integrin expression profile is not suitable for categorizing
      uveal melanomas as less malignant and highly malignant lesions.

PMID- 8258523
TI  - Difference in PNA label intensity between short- and middle-wavelength sensitive
      cones in the ground squirrel retina.
AB  - PURPOSE: Peanut agglutinin lectin (PNA) is known for its selective binding to
      cone cells and to the cone domains of the interphotoreceptor matrix. In the
      current study, the authors investigated whether there is any difference in PNA
      binding between color-specific cones of the cone-dominant ground squirrel.
      METHODS: Consecutive serial sections of the retina of Spermophilus
      tridecemlineatus were reacted alternately with PNA and antivisual pigment
      antibodies. The PNA labels associated with short- and middle-wavelength-sensitive
      cones (S-cones and M-cones, respectively) were compared with fluorescent lectin
      cytochemistry. RESULTS: Although all rod-like cells were left unstained, the
      cones exhibited a specific lectin label. There was, however, a significant
      difference between the two cone types; the intensity of the ring-like PNA label
      in the matrix sheath around S-cones significantly exceeded that of the M-cones.
      CONCLUSIONS: The difference in PNA label intensity indicates a difference in the
      composition of the matrix sheaths surrounding the two respective cone types. To
      the authors' knowledge, this is the first report on lectin-cytochemical
      discrimination of cone matrix sheaths and the first lectin study in the ground
      squirrel retina leading to the observation that PNA can distinguish the three
      characteristic photoreceptor types in this animal. In this respect, the rod-like
      cells of the ground squirrel retina were shown to be no different from rod cells
      of other species.

PMID- 8258524
TI  - The effects of dystrophin gene mutations on the ERG in mice and humans.
AB  - PURPOSE: The authors' earlier findings of a negative electroretinogram (ERG) in a
      boy with Duchenne muscular dystrophy (DMD) led them to investigate dystrophin
      gene deletions and ERGs in five boys with DMD. The authors wanted to determined
      whether there were similar ERG findings in an animal model for DMD, the mdx
      mouse. METHODS: Ganzfeld ERGs were recorded in five boys with DMD after a
      complete ophthalmic examination. The dystrophin gene was analyzed by Southern
      blot hybridization. ERGs were recorded in anesthetized mdx and control mice with
      a modified Grass photostimulator (Grass Instrument Company, Quincy, MA). RESULTS:
      Ophthalmic examinations in all five boys had normal findings, yet an abnormal
      negative ERG was recorded for each subject. The subjects' gene deletions were
      variable, ranging from large deletions to no detectable deletions. The ERGs of
      the mdx mice were normal and did not differ significantly from those of the
      control mice. CONCLUSIONS: The authors believe the unique ERG recorded for the
      human subjects is a manifestation of DMD associated with defects at the
      dystrophin gene locus and represents a new clinical entity. The ERG of the mdx
      mouse may be spared for several reasons, including milder effects of the mouse
      gene defect, differences in muscle and retinal gene product, or species
      differences in the biochemical role of dystrophin. The ERG shows promise of
      becoming a noninvasive diagnostic tool for DMD and its milder allelic forms.

PMID- 8258525
TI  - A feline model of ocular toxoplasmosis.
AB  - PURPOSE. This study was performed to characterize the clinical, serologic,
      histopathologic, and immunohistochemical features of an experimental model of
      ocular toxoplasmosis in cats. METHODS: Seven specific pathogen-free cats were
      inoculated in the right carotid artery with 5 x 10(3) tachyzoites of the ME49
      strain of Toxoplasma gondii. Control cats received heat-killed tachyzoites.
      RESULTS: Progressive, bilateral, multifocal retinal, and choroidal inflammatory
      foci developed in the principal cats, beginning 5 to 8 days postinoculation (PI).
      Lesion development peaked 3 weeks PI, and the lesions varied in size from
      pinpoint to 5 mm, had a predilection for the central tapetal fundus, and were
      more numerous ipsilateral to the side of inoculation. Resolution of the lesions
      21 to 70 days PI was characterized by foci of tapetal destruction and retinal
      degeneration. Fluorescein angiography showed disruption of the blood-retinal
      barrier at the level of the retinal pigmented epithelium, and occasional retinal
      vasculitis and perivasculitis. Mild anterior uveitis developed in four cats 10 to
      13 days PI. Aside from a slight febrile response 2 to 3 days PI, no physical
      abnormalities were observed. T. gondii antigens were detected intermittently in
      the serum of four of seven cats as early as 8 days PI. T. gondii-specific
      immunoglobulin M titers were present on day 7 PI and continued to increase until
      28 days PI. Immunoglobulin G production was documented on day 13 PI, and titers
      continued to increase throughout the study. Evidence of anterior uveal antibody
      production (mean Goldmann-Witmer coefficient [C value], 80.7; range, 13.4 to
      236.6) was present in 11 of 14 eyes on day 70 PI. On histopathologic evaluation
      70 days PI, multifocal granulomatous chorioretinitis, with retinal degeneration,
      retinal vasculitis, and lymphocytic-plasmacytic anterior uveitis, was documented.
      Tissue cysts in the retina and choroid were found with mouse inoculation of
      tissue suspensions, immunohistochemical studies, and histopathologic examination.
      CONCLUSIONS: This nonfatal, noninvasive method of inducing ocular toxoplasmosis
      may prove to be a useful model for investigation of toxoplasmi retinochoroiditis,
      particularly with the recent characterization of a naturally occurring,
      immunosuppressive feline lentivirus with properties similar to human
      immunodeficiency virus.

PMID- 8258526
TI  - Protection of retinal pigment epithelium from oxidative injury by glutathione and
      precursors.
AB  - PURPOSE: This study was performed to examine the effect of exogenous glutathione
      (GSH) or its precursor amino acids on oxidative injury in cultured human retinal
      pigment epithelium (RPE). METHODS: Cultured human RPE cells were suspended in
      Krebs-Henseleit medium, and 150 microM t-butylhydroperoxide was added. Cell
      viability was assessed by 0.2% trypan blue exclusion 30, 60, and 120 minutes
      after the addition of GSH or its amino acid precursors. RESULTS: Added GSH
      provided protection at concentrations of 0.01 mM and higher. The amino acid
      precursors for GSH, glutamate, cysteine, and glycine also protected against
      injury, but this required at least 0.1 mM of each amino acid. Inhibition of
      intracellular GSH synthesis by inclusion of 1 mM buthionine sulfoximine
      eliminated the protection by added amino acids but did not alter the protection
      by added GSH. CONCLUSIONS: These results indicate that protection by the amino
      acid precursors is mediated through synthesis of GSH, and they also show that
      exogenous GSH can provide protection against oxidative injury.

PMID- 8258527
TI  - An opsin homologue in the retina and pigment epithelium.
AB  - PURPOSE: The aim of this project was to investigate the retinal pigment
      epithelium (RPE) at the molecular level by identification of novel RPE-specific
      cDNAs that may encode proteins of signal transduction pathways or other proteins
      that are expressed preferentially in the RPE. METHODS: A bovine RPE cDNA library
      was constructed in bacteriophage lambda g10 using RPE-enriched poly(A)+ RNA. The
      library was screened by differential hybridization to bovine RPE and kidney cDNA
      probes. RESULTS: A member of the hepatahelical receptor family was identified in
      bovine RPE by molecular cloning. Its deduced amino acid sequence predicts a
      protein that has 291 amino acid residues and resembles most closely the family of
      visual pigments. A lysine residue, analogous to the retinaldehyde attachment site
      in rhodopsin, is conserved in the seventh hydrophobic segment of the novel
      sequence. Messenger RNA encoding the putative G protein-coupled receptor was
      detected by in situ hybridization in the RPE, inner nuclear layer, and specific
      cells of the ganglion cell layer. Immunohistochemical staining of bovine retina
      showed that the receptor protein is localized in Muller cells, as well as in the
      RPE. CONCLUSIONS: A novel heptahelical receptor defines a distant evolutionary
      branch of the visual pigment tree. The selective localization of this putative
      receptor, its abundance in RPE and retina, and its homology to the visual
      pigments suggest that the function of this receptor is important in a visual
      process involving the RPE and Muller cells.

PMID- 8258528
TI  - Polymorphonuclear leukocyte infiltration into the subretinal choroid and optic
      nerve in response to leukotrienes.
AB  - PURPOSE: To describe the pattern of leukocyte infiltration in ocular anterior and
      posterior segment tissues in response to local administration of LTB4 and LTD4.
      METHODS: Leukocyte infiltration after intravitreal administration of LTB4 or LTD4
      was assessed in ocular sagittal cross-sections and compared with vehicle-treated
      control eyes. RESULTS: A dose-dependent eosinophil infiltration was observed in
      the subretinal choroid and the ora serrata region of the ciliary body in response
      to both LTB4 and LTD4, but only LTB4 behaved as a chemoattractant for
      neutrophils. Subretinal eosinophils achieved Bruch's membrane in response to LTB4
      but, though gathered in several foci, this important barrier was not breached and
      leukocytes did not reach the neural retina. Eosinophils and some neutrophils also
      achieved the optic disc in response to LTB4. Tissue damage to the optic nerve
      head coincided with the presence of degranulating eosinophils, indicating that
      visual impairment may result from damage to the optic nerve head, with the retina
      left intact. Apart from the ora serrata and pars plana, no leukocyte infiltration
      in other anterior segment tissues--such as the pars plicata, ciliary process, or
      iris proper--was apparent. CONCLUSIONS: It appears that the ingress of leukocytes
      into intraocular tissues of the eye in response to leukotrienes is discretely
      regulated, probably at the level of the vasculature.

PMID- 8258529
TI  - Outcome after very early treatment of dense congenital unilateral cataract.
AB  - PURPOSE: To evaluate whether very early treatment for congenital unilateral
      cataract results in better long-term functional outcomes, grating acuity,
      contrast sensitivity, recognition acuity, and random-dot stereoacuity were
      evaluated in two groups of children. METHODS: Grating acuity and contrast
      sensitivity data were obtained with standard forced-choice protocols.
      Stereoacuity data were obtained both in a forced-choice laboratory protocol and
      by the Randot test. RESULTS: Immediately after treatment, both the very early (1
      to 6 weeks; n = 8) and early (2 to 8 months; n = 6) treatment groups showed a 0.3
      log unit grating acuity deficit in the aphakic eye. Grating acuity in the early
      group showed some improvement with age but reached a plateau of 0.75 logMAR at 18
      to 24 months; the very early group showed more improvement and reached a plateau
      of 0.22 logMAR at 37 to 48 months. At 5 to 8 years of age, aphakic eyes of the
      very early group had significantly better contrast sensitivity and recognition
      acuity than the aphakic eyes of the early group. Overall, grating acuity deficits
      during years 2 through 5 were significantly correlated with contrast sensitivity
      and recognition acuity outcomes measured at 5 to 8 years of age. No deficits in
      grating acuity, contrast sensitivity, or recognition acuity were found for phakic
      fellow eyes in either group. Three children in the very early treatment group
      (37.5%) were orthotropic and demonstrated gross random-dot stereopsis; one child
      in the early group was orthotropic but none of these children demonstrated random
      dot stereopsis. CONCLUSIONS: These results suggest that treatment initiated at 1
      to 6 weeks of age maximizes the opportunity for normal or near-normal visual
      development of a congenitally cataractous eye with little or no risk to the
      phakic fellow eye.

PMID- 8258530
TI  - Variability of the main sequence.
AB  - PURPOSE: This study investigated the relationship between amplitude and peak
      velocity of saccadic eye movements (the so-called main sequence) and the intra
      individual variability of the main sequence. METHODS: Saccadic amplitudes and
      peak velocities were measured twice in 58 healthy subjects with an infrared
      reflection technique. RESULTS: Considerable intra-individual variability was
      found between the first and second recordings. CONCLUSIONS: Intra-individual
      variability of saccadic peak velocity affects the interpretation of changes in
      repeated recordings of peak velocities, such as before and after medication is
      administered. Furthermore, considerable intra-individual variability decreases
      the probability that statistically significant differences between patients and
      control subjects can be detected, especially when groups are small. Calculating
      the intraclass correlation coefficient allows the number of subjects in
      comparative studies to be determined.

PMID- 8258531
TI  - Promoting the health and fitness of osteopathic medical students.

PMID- 8258533
TI  - Magnetic resonance angiography.
AB  - Magnetic resonance angiography is a noninvasive approach to vascular study that
      recently has become feasible and is quickly proving its usefulness in several
      areas. Currently, advances are concentrated on evaluation of vessels of the head
      and neck. Magnetic resonance angiography has also proved valuable in evaluation
      of the central vasculature, including the heart. Because magnetic resonance
      angiography is not a single technique and the different techniques of which it is
      composed have their own strengths and weaknesses, it is important that
      clinicians, as well as radiologists, be aware of these strengths and weaknesses.
      Various techniques and their applications and limitations are discussed.

PMID- 8258532
TI  - Do medical students' knowledge and attitudes about health and exercise affect
      their physical fitness?
AB  - This study examined the relationship between unselected first-year medical
      students' knowledge and attitudes about health or exercise and their personal
      physical fitness. The 131 subjects performed a maximal exercise test to determine
      physical fitness by measuring maximal oxygen consumption (VO2max), underwent
      hydrostatic weighing to assess body fat content (percent body fat), and completed
      a questionnaire to measure their knowledge and attitudes about health
      promotion/disease prevention and exercise. Many independent variables were
      significantly associated with VO2max in bivariate analyses, but only percent body
      fat, resting systolic blood pressure, and perceived barriers to health
      promotion/disease prevention and to exercise were significant predictors of
      VO2max (mL x kg-1 x min-1) in the multivariate analyses. The absolute VO2max (L x
      min-1) can be predicted from percent body fat, weight, and perceived barriers to
      health promotion/disease prevention. Freshmen medical students' attitudes toward
      health promotion/disease prevention and exercise constitute one of three strong
      predictors of physical fitness levels and should be determined, along with
      percent body fat and resting systolic blood pressure, when estimating fitness
      levels in a medical student population.

PMID- 8258534
TI  - Computed tomography in the diagnosis and management of popliteal artery
      entrapment syndrome.
AB  - Popliteal artery entrapment by an anomalous band of the gastrocnemius muscle is
      an uncommon but apparently under-diagnosed syndrome. Historically, arteriography
      has been used to diagnose this condition, but the standard method may not
      demonstrate arterial deviation or differentiate entrapment from other conditions
      that affect the popliteal artery, such as cystic adventitial disease and
      thrombosed popliteal artery aneurysms. Computed tomography has become
      increasingly useful to vascular surgeons in elucidating arterial disorders of the
      popliteal fossa. This case demonstrates the usefulness of computed tomography
      evaluation in the diagnosis and management of popliteal artery entrapment.

PMID- 8258535
TI  - Lifestyle changes associated with osteopathic medical education.
AB  - A written survey of second-year osteopathic medical students at West Virginia
      School of Osteopathic Medicine was conducted to determine if detrimental
      lifestyle changes had occurred in the first 15 months of their medical education.
      Fifty-two (79%) of the 66 students returned the survey. The large majority of the
      responders (96%) reported a detrimental alteration in at least one area, and 81%,
      in two or more of the four areas surveyed. Changes in eating patterns were
      indicated by 79% of responding students. Increases in caffeinated beverage
      consumption were reported by 71% of respondents, and decreases in activity level,
      by 78%. Weight gains were indicated by 64% of respondents. Entering students
      should be advised of the risk that detrimental lifestyle changes may occur during
      their osteopathic medical education and be encouraged to prevent these harmful
      changes.

PMID- 8258536
TI  - A primer on graduate medical education financing.
AB  - Medical education is recognized as a legitimate cost of doing business in a
      teaching hospital. This article outlines the general principles and concepts
      currently used to determine the actual amount of financial reimbursement that a
      hospital receives for its graduate medical education (GME) programs. Directors of
      Medical Education should have a solid understanding of these principles if they
      are to work successfully with the hospital reimbursement experts to maximize the
      teaching hospital's revenue. To that end, the authors detail 10 rules to ensure
      that all essential elements are included in the reimbursement formulas. Also
      considered are the nonfinancial benefits of GME of which hospital leadership must
      be aware so that they may understand the total contribution that GME makes to the
      teaching hospital.

PMID- 8258537
TI  - More comments on the call to reform the profession.

PMID- 8258538
TI  - More comments on the call to reform the profession.

PMID- 8258539
TI  - More comments on the call to reform the profession.

PMID- 8258540
TI  - More comments on the call to reform the profession.

PMID- 8258541
TI  - An MD's note to his osteopathic medical students.

PMID- 8258542
TI  - Fracture classification systems: do they work and are they useful?

PMID- 8258543
TI  - The Neer classification system for proximal humeral fractures. An assessment of
      interobserver reliability and intraobserver reproducibility.
AB  - The radiographs of fifty fractures of the proximal part of the humerus were used
      to assess the interobserver reliability and intraobserver reproducibility of the
      Neer classification system. A trauma series consisting of scapular
      anteroposterior, scapular lateral, and axillary radiographs was available for
      each fracture. The radiographs were reviewed by an orthopaedic shoulder
      specialist, an orthopaedic traumatologist, a skeletal radiologist, and two
      orthopaedic residents, in their fifth and second years of postgraduate training.
      The radiographs were reviewed on two different occasions, six months apart.
      Interobserver reliability was assessed by comparison of the fracture
      classifications determined by the five observers. Intraobserver reproducibility
      was evaluated by comparison of the classifications determined by each observer on
      the first and second viewings. Kappa (kappa) reliability coefficients were used.
      All five observers agreed on the final classification for 32 and 30 per cent of
      the fractures on the first and second viewings, respectively. Paired comparisons
      between the five observers showed a mean reliability coefficient of 0.48 (range,
      0.43 to 0.58) for the first viewing and 0.52 (range, 0.37 to 0.62) for the second
      viewing. The attending physicians obtained a slightly higher kappa value than the
      orthopaedic residents (0.52 compared with 0.48). Reproducibility ranged from 0.83
      (the shoulder specialist) to 0.50 (the skeletal radiologist), with a mean of
      0.66. Simplification of the Neer classification system, from sixteen categories
      to six more general categories based on fracture type, did not significantly
      improve either interobserver reliability or intraobserver reproducibility.

PMID- 8258544
TI  - The reproducibility of classification of fractures of the proximal end of the
      humerus.
AB  - The radiographs of ninety-five fractures of the proximal end of the humerus were
      classified with the Neer and the AO/ASIF systems by five orthopaedic surgeons who
      had a special interest in problems of the shoulder. Without access to their
      initial interpretations, the same five orthopaedic surgeons reevaluated the same
      radiographs eight weeks later. Intraobserver and intraobserver reliability were
      found to be fair or poor for both classification systems. Kappa values for the
      interobserver reliability were 0.40 for the Neer system and 0.53 for the AO/ASIF
      system. When the fractures were subclassified, according to the recommendations
      of the AO/ASIF, into groups and subgroups, reproducibility became progressively
      worse. Intraobserver reliability showed kappa values of 0.60 and 0.58,
      respectively. A so-called extended radiographic trauma series, consisting of
      three perpendicular radiographs, was available for thirty-five fractures; the
      third perpendicular projection did not significantly improve the reproducibility
      values for either classification compared with those obtained with only two
      perpendicular projections. We concluded that neither the Neer nor the AO/ASIF
      classification of fractures of the proximal end of the humerus is sufficiently
      reproducible to allow meaningful comparison of similarly classified fractures in
      different studies.

PMID- 8258545
TI  - Experimental physeal fracture-separations treated with rigid internal fixation.
AB  - Salter-Harris Type-III and Type-IV epiphyseal injuries were created in the distal
      aspect of the femur in growing rabbits, and the healing process was analyzed both
      in the absence of any treatment and after treatment with anatomical reduction and
      fixation with compression with use of a cortical screw. A sham operation was
      performed on the left knee, to create a control group. Untreated Type-III
      injuries led to an angular deformity of the femur that became more severe with
      time. In the group that had an untreated Type-IV injury, a step-off developed on
      the articular surface and increased with time. Early vascular anastomoses between
      the epiphysis and the metaphysis preceded the formation of osseous bridges in
      these lesions. The healing process in the animals that were treated with
      anatomical reduction and rigid internal fixation occurred without the formation
      of osseous callus, and no marked abnormalities were discernible in the physis.

PMID- 8258546
TI  - Deformity following fracture in diabetic neuropathic osteoarthropathy. Operative
      management of adults who have type-I diabetes.
AB  - We studied fifteen lower extremities that had a deformity following a fracture in
      the region of the ankle or the tarsal bones, in fourteen adults who had type-I
      diabetes and neuropathic osteoarthropathy. The skeletal deformities associated
      with these fractures were either diagnosed late (two limbs) or occurred in lower
      extremities that had been treated by means other than non-weight-bearing and
      immobilization (thirteen limbs). All deformities were severe and secondary to a
      non-union or malunion of the fracture; all were ultimately treated with operative
      reconstruction. Before the reconstruction, the limbs had had either persistent
      ulceration associated with an uncorrectable skeletal deformity (four) or a severe
      deformity that was difficult to contain with a custom-made orthosis (eleven). The
      most recent result was considered a success when the ulceration had healed, the
      involved foot was planti-grade, and the involved limb was capable of bearing
      weight with use of a patellar tendon-bearing orthosis. Following reconstruction,
      ten patients had a plantigrade foot without ulceration, three had a plantigrade
      foot with a persistent draining ulcer, and one had a foot that was not
      plantigrade. In the limbs that had an ulcer at the time of the operation, there
      was one successful outcome and three failures. In contrast, the outcome was
      successful for ten of the limbs that had not had an ulcer and a failure for one.
      There were three complications following sixteen operative reconstructive
      procedures in the fourteen patients, including one infection and two instances of
      accelerated bone resorption and collapse.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258547
TI  - Plate fixation of femoral shaft fractures in multiply injured children.
AB  - A study was done of twelve patients (seven boys and five girls) who, because of
      multiple injuries or a head injury, had been managed with compression plating of
      a unilateral or bilateral femoral-shaft fracture at a level-I trauma center from
      1986 through 1990. The patients had a total of fifteen fractures. The average age
      at the time of the injuries was eight years (range, five years to nine years and
      eleven months). There were nine closed fractures and six open fractures; three of
      the open fractures were Grade I; two, Grade II; and one, Grade IIIA, according to
      the criteria of Gustilo et al. Each patient had an average of three associated
      injuries. All fifteen fractures had healed clinically and radiographically at an
      average of eight weeks (range, six to twelve weeks) after the operation. There
      were no infections. Anatomical alignment was obtained in fourteen limbs. One
      fracture healed with 13 degrees of anterior angulation. The compression plates
      were removed at an average of ten months (range, three to twenty-four months)
      after the index operation. At the latest follow-up evaluation (average, twenty
      six months; range, eleven to fifty-seven months), no patient had restriction of
      activities due to the femoral fracture. Scanograms revealed overgrowth of the
      injured femur averaging 0.9 centimeter (range, 0.3 to 1.4 centimeters) in seven
      patients who had an uninjured contralateral femur. We believe that plate fixation
      of the femur is a good treatment option for children who have a femoral shaft
      fracture and a major head injury or multiple injuries, or both.

PMID- 8258548
TI  - Myoelectric prostheses. A long-term follow-up and a study of the use of alternate
      prostheses.
AB  - Forty-four patients who had had a total of forty-seven amputations of an upper
      extremity and who had had a myoelectric prosthesis for more than two years were
      evaluated retrospectively for the amount of use of the prosthesis, the use of any
      other prosthesis, and the demographic factors that might be related to use of the
      prosthesis. The average duration of follow-up was five years (range, twenty-five
      months to seventeen years). Forty of the forty-four patients also had a
      conventional prosthesis. Twenty-two patients (50 per cent) rejected the
      myoelectric prosthesis completely; thirteen (32 per cent) of the forty patients
      who also had a conventional prosthesis rejected the conventional prosthesis
      completely. The patients who used the myoelectric device the least were employed
      in occupations that required high-demand use of the prosthesis (lifting of more
      than 4.5 kilograms [ten pounds] or repetitive manual labor) or were receiving or
      seeking Workers' Compensation, or both.

PMID- 8258549
TI  - Treatment of cysts of the acromioclavicular joint with shoulder hemiarthroplasty.
AB  - A chronic cyst overlying the acromioclavicular joint was managed in four
      patients, between July 1988 and September 1991. All patients had had previous
      unsuccessful aspiration and excision of the cyst with recurrence. Each cyst was
      associated with a chronic, massive defect of the rotator cuff; superior migration
      of the humeral head; and degenerative osteoarthrosis of the glenohumeral joint.
      All patients had complained of pain and limitation of motion (mean forward
      elevation, 95 degrees; mean external rotation, 20 degrees; and mean internal
      rotation, to the spinous process of the second lumbar vertebra). All procedures
      consisted of a large-humeral-head hemiarthroplasty, with no operative treatment
      directed at the cyst or the acromioclavicular joint. At an average of twenty
      seven months (range, fifteen to thirty-six months) after the operation, the
      patients were all pain-free and had not had a recurrence of the cyst. The average
      postoperative range of motion was 130 degrees of forward elevation, 30 degrees of
      external rotation, and internal rotation to the spinous process of the first
      lumbar vertebra.

PMID- 8258550
TI  - Tendon-healing in a bone tunnel. A biomechanical and histological study in the
      dog.
AB  - Our study evaluated tendon-to-bone healing in a dog model. Twenty adult mongrel
      dogs had a transplantation of the long digital extensor tendon into a 4.8
      millimeter drill-hole in the proximal tibial metaphysis. Four dogs were killed at
      each of five time-periods (two, four, eight, twelve, and twenty-six weeks after
      the transplantation), and the histological and biomechanical characteristics of
      the tendon-bone interface were evaluated. Serial histological analysis revealed
      progressive reestablishment of collagen-fiber continuity between the bone and the
      tendon. A layer of cellular, fibrous tissue was noted between the tendon and the
      bone, along the length of the bone tunnel; this layer progressively matured and
      reorganized during the healing process. The collagen fibers that attached the
      tendon to the bone resembled Sharpey fibers. High-resolution radiographs showed
      remodeling of the trabecular bone that surrounded the tendon. At the two, four,
      and eight-week time-periods, all specimens had failed by pull-out of the tendon
      from the bone tunnel. The strength of the interface was noted to have
      significantly and progressively increased between the second and the twelfth week
      after the transplantation. At the twelve and twenty-six-week time-periods, all
      specimens had failed by pull-out of the tendon from the clamp or by mid-substance
      rupture of the tendon. The progressive increase in strength was correlated with
      the degree of bone ingrowth, mineralization, and maturation of the healing
      tissue, noted histologically.

PMID- 8258551
TI  - Progression of the curve in boys who have idiopathic scoliosis.
AB  - The prevalence of curve progression was evaluated in 210 boys who had idiopathic
      scoliosis. A minimum age of eight years, a deformity of at least 10 degrees, and
      radiographic follow-up of one year or progression of the curve within the first
      year of follow-up were the criteria for inclusion in the study. Of the 210
      patients, sixty-eight (32 per cent) had progression of 10 degrees or more. Four
      of the five patients who had had an initial curve of 50 degrees or more
      subsequently had a spinal arthrodesis. The risk of progression was significantly
      greater for patients who were at an earlier Risser stage (p < 0.002) and for
      those who were younger (p < 0.005). The risk of progression was also greater for
      patients who had had a larger curve at the time of presentation; of the sixty
      three boys for whom the Risser grade was 1, 2, 3, 4, or 5 when they were first
      seen and who had a curve of 25 degrees or more, twenty (32 per cent) had
      progression, compared with only two (5 per cent) of the thirty-eight who had a
      Risser grade of 1, 2, 3, 4, or 5 and a curve of 24 degrees or less. Of the thirty
      four patients for whom the Risser grade was 4 when they were first seen, five (15
      per cent) had progression.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258552
TI  - Musculoskeletal melioidosis.
AB  - During a four-year period, twenty-one patients were found to have melioidosis of
      the musculoskeletal system caused by Pseudomonas pseudomallei. The melioidotic
      patients were matched with thirty-nine patients who had a musculoskeletal
      infection due to some other organism, and the two groups were compared with
      regard to the presence of concurrent disease. The indirect hemagglutination test
      for melioidosis was positive for all of the melioidotic patients; in thirteen,
      cultures also were positive. For the patients who did not have melioidosis, the
      diagnosis was made on the basis of positive cultures of other organisms or
      histological sections. In most of the non-melioidotic patients, the infection was
      due to Staphylococcus aureus (twenty-four patients) or to Mycobacterium
      tuberculosis (twelve patients). The most common concurrent diseases in the
      melioidotic patients were diabetes and thalassemia. The odds that melioidosis was
      the cause of the infection in a patient who had a concurrent disease were twelve
      to one. All melioidotic patients were managed with operative debridement and a
      combination of drugs--usually, trimethoprim and sulfamethoxazole, doxycycline,
      and kanamycin or chloramphenicol--for six months. The mean duration of follow-up
      was one and one-half years. Of the twenty-one patients, eighteen had an excellent
      or good result in terms of motion of the joint and absence of relapse.

PMID- 8258553
TI  - Diagnosis of infection in ununited fractures. Combined imaging with indium-111
      labeled leukocytes and technetium-99m methylene diphosphonate.
AB  - The results of combined scintigraphy in which indium-111-labeled leukocytes and
      technetium-99m methylene diphosphonate were used were compared with the results
      of cultures of open bone at 102 sites of delayed union or non-union, to determine
      the effectiveness of this combination as a preoperative indicator of
      osteomyelitis. There were twenty-five true-positive, fifty-nine true-negative,
      eleven false-positive, four false-negative, and three indeterminate
      interpretations, yielding, for the diagnosis of osteomyelitis, a sensitivity of
      86 per cent, a specificity of 84 per cent, an accuracy of 82 per cent, a positive
      predictive value of 69 per cent, and a negative predictive value of 94 per cent.
      There were few false-negative scans; false-positive results were most likely at a
      metaphyseal site adjacent to a joint in which there was post-traumatic
      arthropathy, at the site of a failed arthrodesis, and at the site of an unstable
      delayed union or non-union.

PMID- 8258554
TI  - The results of operations on the lumbar spine in patients who have diabetes
      mellitus.
AB  - The results for sixty-two patients who had had a diagnosis of diabetes mellitus
      and lumbar disc disease or spinal stenosis and had been managed with a posterior
      decompressive procedure were compared, in a retrospective study, with those for
      sixty-two age and sex-matched non-diabetic (control) patients who had had similar
      operative procedures. Forty-four of the sixty-two diabetic patients and fifty
      five of the non-diabetic patients were available for long-term follow-up (mean,
      five and seven years, respectively). Among the diabetic patients, there were high
      rates of postoperative infection and prolonged hospitalization compared with the
      rates for the control group. The long-term result was excellent or good for
      seventeen (39 per cent) of the forty-four patients who had diabetes mellitus and
      for fifty-two (95 per cent) of the fifty-five non-diabetic patients. The poor
      results in the diabetic patients may have been related to coexisting diabetic
      neuropathy, to the associated microvascular disease that affects the spinal nerve
      roots in diabetic patients, or to the failure of the nerve roots of these
      patients to recover after decompressive procedures.

PMID- 8258555
TI  - Solitary osteoma of a long bone. A case report.

PMID- 8258556
TI  - Extrapleural abscess secondary to infection of the sternoclavicular joint. Report
      of two cases.

PMID- 8258557
TI  - Bilateral pelvitrochanteric heterotopic ossification in a child. A case report.

PMID- 8258558
TI  - The need for confidence intervals in the presentation of orthopaedic data.

PMID- 8258559
TI  - Thallium-201 scanning for the evaluation of osteosarcoma and soft-tissue sarcoma.

PMID- 8258560
TI  - Melting pot or mosaic.

PMID- 8258561
TI  - Four decades of change.

PMID- 8258562
TI  - The dental literature: a reflection of changes in dentistry for children.

PMID- 8258563
TI  - The little mysteries in our chairs.

PMID- 8258564
TI  - Hospital pediatric dentistry: at the crossroads again.

PMID- 8258565
TI  - The oral health of our children: telling governments we have not completed the
      job.

PMID- 8258566
TI  - Restorative dentistry materials for children: the 1990's and beyond.

PMID- 8258567
TI  - A pedodontic beacon.

PMID- 8258568
TI  - Alfred Kantorowicz, pediatric dentistry innovator.
AB  - Alfred Kantorowicz was born in 1880. He received his dental degree in 1900 and
      his medical degree in 1906. After World War I he became the director of the
      dental institute in Bonn, Germany. He was an amazing leader with a special
      interest in pediatric dentistry and was the developer of mobile clinics and
      preventive dentistry programs for children in Germany. In the 1930s and 1940s, he
      was instrumental in modernizing the dental curriculum in Turkey. He died in 1962
      in Germany.

PMID- 8258569
TI  - Pharmacologic patient management in pediatric dentistry: an update.
AB  - This paper reviews the issue of sedation in pediatric dentistry in the light of
      recent controversies and rapidly increasing legal, professional and governmental
      regulations. Consideration is given to "Guidelines for safe administration of
      pharmacologic agents in dental practice". The various avenues of drug
      administration are reviewed with specific comment on recent approaches. Many of
      the older pharmacologic agents used for pediatric sedation are falling into
      disfavor. Chloral hydrate, in particular, would seem to be heading toward its
      demise. The benzodiazepines appear to have a very promising future as sedative
      agents. When administered and monitored appropriately, they have a wide margin of
      safety. Consideration is given to research and development into agents that
      reverse the action of sedative drugs. It is emphasized that contemporary
      electronic monitoring equipment in no way diminishes the necessity for sound and
      expert clinical judgment, supplemented by such simple devices as the precordial
      stethoscope and observation and communication in the form of simple commands.

PMID- 8258570
TI  - Dental management of child and adolescent patients with schizophrenia.
AB  - Schizophrenia is a psychiatric disorder in which thought disturbances and
      aberrant behavior lessen an individual's ability to care for him or herself and
      to effectively work and communicate with others. The disorder affects 1 percent
      of the United States population. Onset of the florid psychotic symptoms most
      commonly occurs during adolescence or young adulthood, but most of these
      youngsters exhibit unusual behavior and peculiar thinking during childhood.
      Medications used in managing the disorder have numerous systemic and orofacial
      adverse side effects that must be recognized by dentists. Dental treatment
      strategies for the identification and management of these side effects are
      described as is a method to improve compliance with oral hygiene techniques.

PMID- 8258571
TI  - An assessment of the success of meperidine and promethazine sedation in medically
      compromised children.
AB  - A retrospective study evaluated the success of orally administered meperidine
      (1.0 mg/lb) and promethazine (0.5 mg/lb) combined with N20:02, and determined
      predictors of success in a medically, physically and/or mentally compromised
      population. Behavior of 143 uncooperative patients (mean age 6.4 years) was
      evaluated during 282 sedations. A simplified Success Index rated outcome: 1
      failure, 2-moderately successful; 3-highly successful. Variables were examined
      for effect on outcome of sedation: physical and/or neurologic component of
      medical diagnosis; previous hospital experience; medication category. Children
      taking medications with CNS actions were significantly less likely to have either
      moderately successful (p = .008) or highly successful appointments (p = .002).
      Children with a neurologic component to their medical diagnosis were
      significantly less likely to have a highly successful appointment (p = .001).
      Oral sedation was effective for this population (77 percent were successful) and
      certain characteristics of the patient's condition can predict success.

PMID- 8258572
TI  - Experience with midazolam as sedative in the dental treatment of uncooperative
      children.
AB  - Shortage of capacity, and the limited range of therapies available for dental
      treatment of uncooperative children involve obvious problems which have given
      rise to new developments in treatment. Over the last two years, 83 children have
      been treated in 181 sessions after sedation with Midazolam. Rectal application is
      clearly superior to giving the drug orally. The results, and the good amnestic
      effect of Midazolam show that sedation employing this drug, while not a
      substitute for general anaesthesia in every case, does constitute an important
      alternative in the treatment of uncooperative children.

PMID- 8258573
TI  - Caries protection after orthodontic band cementation with glass ionomer.
AB  - This study evaluated the resistance of the enamel to an artificial caries
      challenge after removing orthodontic bands cemented with a glass ionomer cement
      (GIC). Ten extracted caries-free molars were cleaned with a slurry of pumice and
      randomly divided into 2 groups of 5 teeth each: Group 1: Cementation with GIC
      (Fuji) and Group 2: Cementation with a zinc phosphate cement (Mizzy). Both
      cements were handled according to manufacturer's instructions. Before cementing
      the bands, an area of S x S mm was masked with adhesive tape on the lingual
      surfaces of all teeth. The orthodontic bands were cemented over this adhesive
      tape. After band cementation, the occlusal and gingival margins of the band were
      delineated with a bur on the tooth surface. The teeth were thermocycled (200
      cycles, 5-55 degrees C, 30-second dwell time) and stored in distilled water for
      24 hours. Then, the bands and adhesive tape were removed and the teeth again
      stored in distilled water for a week, changing the water daily. The teeth were
      then varnished with the exception of a 5 x 5 mm window (including previously
      exposed and covered areas) on the buccal and lingual surfaces. All teeth were
      then placed in an acidified gel (pH 4.5) for 5 weeks to produce artificial
      caries. At least three sections from the exposed and covered areas were made from
      the buccal and lingual challenged areas. Sections were ground to approximately
      100 microns. Polarized microscopy and image analysis were used to analyze the
      results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258574
TI  - Comparison of two methods for evaluating the occlusal marginal adaptation of
      posterior restorations.
AB  - Two methods of evaluating the occlusal marginal adaptation of posterior
      restorations are compared: a direct and an indirect method. The direct method
      uses modified Ryge criteria and assessments are performed with mirror, probe and
      operating lamp. With the indirect method assessments are conducted using
      photographs of impressions of the restorations. For the purpose of the comparison
      a selected group of newly placed amalgam and composite restorations is used and
      attention is paid to a 'section method' of observation. This routine of
      localization the parts of the outline to be measured, permits independent
      comparison of the assessments. The two methods were applied by pairs of observers
      and the indirect photographic method appears to be more reliable (percentual
      agreement between observers 97 percent versus 80-91 percent for the direct
      method). The agreement between the indirect and direct methods is rather low. The
      indirect photographic method is more valid when compared to a yardstick,
      especially if few deficiencies of the margin are expected. It is not clear which
      method is preferable if more deficiencies occur with restorations of higher age.

PMID- 8258575
TI  - Evaluation of occlusal marginal adaptation of Class II resin-composite
      restorations.
AB  - This paper describes the results of an evaluation of the occlusal marginal
      adaptation of Class II restorations in a clinical trial. The margins of 183 resin
      composite and 61 amalgam restorations, made by three dentists, were assessed. An
      indirect evaluative method has been applied, that uses a shadowing photographic
      technique to produce images of impressions. The restorations were classified into
      excellent and nonexcellent marginal adaptation categories and on this basis
      influencing factors were determined. Resin composite restorations appeared to
      show more 'excellent' margins than amalgam restorations (64.5 percent and 21.3
      percent, respectively). The variable mainly influencing the marginal adaptation
      of the composite restorations was the dentist. In addition, the influence of an
      occlusal level is discussed, since a difference of marginal adaptation between
      bevelled and nonbevelled parts of the occlusal outline was observed.

PMID- 8258576
TI  - Specialist clinicians' perceptions of dental fluorosis.

PMID- 8258577
TI  - A statewide survey of dentists' knowledge of abuse.

PMID- 8258578
TI  - Your next pediatric dental patient may have been physically or sexually abused.
AB  - A virtual epidemic of physical, sexual and emotional abuse is spreading to even
      the youngest of our children. Pediatric practitioner awareness of potential
      problems must be incorporated into efforts to establish a working relationship
      with children--even those in the "best of families." Data are presented to
      provide some dimensions of the problem.

PMID- 8258579
TI  - Single parent families.

PMID- 8258580
TI  - Supernumerary rooted primary central incisors: report of seven cases.

PMID- 8258581
TI  - Occlusal caries diagnosis: a changing challenge for clinicians and
      epidemiologists.
AB  - The diagnosis of occlusal caries is an integral part of an epidemiologist's task,
      whether carrying out cross-sectional national caries prevalence surveys to assist
      with planning and the evaluation of service provision, or clinical trials of
      caries preventive agents. Similarly, the clinician also carries out this same
      overall diagnostic procedure in order to plan care for individual patients,
      although he/she will usually have access to improved facilities and diagnostic
      aids. This paper reviews the different problems now being encountered by both
      epidemiologists and clinicians in the face of changes in the presentation of the
      disease at this site and the qualifications which should now be appreciated when
      extrapolating from the results of surveys employing comparatively gross criteria.
      It explores recent developments in diagnostic aids and makes suggestions as to
      how further information might be obtained in future which would aid the valid
      comparison of diagnoses made by these two groups of dentists.

PMID- 8258582
TI  - Performance of electrical resistance measurements adjunct to visual inspection in
      the early diagnosis of occlusal caries.
AB  - The detection of small carious lesions at occlusal surfaces is a difficult task,
      particularly in low caries prevalence populations and individuals. The aim of
      this study was to evaluate the performance of electrical resistance measurements
      (ERM) in diagnosing small dentinal lesions at one site per occlusal surface in
      low caries prevalence populations when used adjunct to visual inspection, and to
      compare the performance of ERM to that of radiographic examination. The occlusal
      surfaces of 81 third permanent molar teeth extracted from young adolescents were
      diagnosed by four examiners, who measured the electrical resistance of enamel on
      a one measurement per surface basis, and furthermore assessed the occlusal
      surfaces visually and radiographically. The teeth were sectioned for validation
      by histological examination. The ERM had the highest sensitivity (0.67), and
      visual inspection had the highest specificity (0.89). ROC analysis showed no
      statistically significant differences between the performance of the observers
      when using visual inspection and ERM (z-score test; P > 0.05). One examiner
      performed statistically significantly better by measuring the electrical
      resistance of enamel than by radiographic examination (P < 0.05). The average
      sensitivity and specificity of the three diagnostic systems were used to express
      the positive and negative predictive values as a function of caries prevalence.
      At a caries prevalence of 0.2 the negative predictive values for visual
      inspection, ERM and radiographic examination were 0.88, 0.91 and 0.89, and the
      positive predictive values were 0.53, 0.48 and 0.42 respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258583
TI  - Five-year study of Class II restorations in permanent teeth using amalgam, glass
      polyalkenoate (ionomer) cerment and resin-based composite materials.
AB  - The aim of this study was to compare the clinical performance of an amalgam, a
      glass polyalkenoate (ionomer) cerment material and a resin-based composite
      material used in small Class II cavities in permanent teeth. All restorations
      were inserted under rubber dam. They were examined yearly for 3 years. One
      clinician continued the study up to 5 years. The clinical examination focused on
      two criteria: clinically acceptable and failure. In addition, impressions were
      taken of the prepared cavities immediately before restoration and at each
      clinical examination using an elastomeric material. The study comprised 274 Class
      II restorations (88 amalgams, 95 cerments and 91 resin composites) placed in 142
      adolescent patients. One hundred and sixty-seven restorations were in molar and
      107 in premolar teeth. Patient dropout after 5 years resulted in the loss of 161
      restorations, evenly distributed for restorative material and type of tooth
      involved. Four amalgam restorations, 22 glass ionomer cerment and nine resin
      composite restorations failed. The glass ionomer cerment and amalgam restorations
      failed primarily due to bulk fractures, while the resin composite restorations
      failed due to secondary caries and bulk fractures.

PMID- 8258584
TI  - Effect of delayed light curing of a resin composite on marginal integrity in
      cylindrical dentine cavities.
AB  - The effect of delayed light curing of resin composite on marginal adaptation has
      been examined by measuring the wall-to-wall polymerization contraction gap when
      using a commercial resin composite together with experimental dentine bonding
      systems to restore cylindrical preparations in dentine. Morphological changes in
      dentine during dentine bonding procedures were observed using a scanning electron
      microscope. In a previous report, the contraction gap width for a resin composite
      increased when irradiation of the resin system was delayed, despite the use of a
      dentine bonding system considered to be 'contraction' gap free. Such
      deterioration in marginal adaptation was minimized by use of an experimental
      dentine primer, 40% erythritol methacrylate aqueous solution (EM), followed by
      the use of a commercial dual- or autocured dentine bonding agent. Under scanning
      electron microscopy, the dentine surface microstructure became unclear after EM
      priming, and a polymer film was detected after polymerization of the dual-cured
      dentine bonding agent. The hydrogelled primer and the formation of a polymer
      network on the dentine surface may prevent the flow of fluid from the pulp
      through the dentine tubules, and maintain marginal integrity if there is delay in
      light curing of light-activated resin composite systems.

PMID- 8258585
TI  - Handling characteristics of gallium alloy for dental restoration.
AB  - The handling characteristics of a gallium alloy (Gallium Alloy GF) were compared
      to those of a spherical high-copper amalgam (Tytin). Ten dentists each restored
      four identical MO preparations in acrylic typodont teeth (no. 30), two with
      amalgam and two with gallium alloy. Each restoration was evaluated immediately
      following completion by the operator for six clinically relevant criteria. Each
      criterion was scored between 1 and 5, where 1 = very poor, 2 = poor, 3 = fair, 4
      = good, and 5 = very good. Three two-sided Mann-Whitney tests were used to
      compare the median scores for significant differences (P < 0.05). The first test
      indicated no significant difference between scores for the first- and second
      placed restorations, within criteria and within alloy type (n = 10). The second
      test indicated a significant difference between amalgam and gallium alloy, within
      criteria and within restoration sequence (n = 10), for each criterion except
      resistance to fracture during removal of the matrix band. The third test
      indicated a significant difference between amalgam and gallium alloy, within each
      criteria, combining scores for first- and second-placed restorations (n = 20).
      During simulated clinical placement, amalgam was rated significantly higher than
      gallium alloy in each handling characteristic evaluated.

PMID- 8258586
TI  - Consultant opinion on orthodontic treatment plans used by dental practitioners: a
      pilot study.
AB  - Prior to 1987, dental practitioners in England and Wales intending to carry out
      all but the simplest orthodontic treatment within the National Health Service,
      were required to submit pretreatment study models, details of the orthodontic
      assessment and the proposed treatment plan to the Dental Estimates Board prior to
      starting treatment. Models taken at the end of treatment were required by the
      Board to enable payment to be made. In this pilot study, the acceptability of
      orthodontic treatment plans used by practitioners working in the General Dental
      Services was assessed by eight hospital consultants, using information about 40
      cases submitted to the Dental Estimates Board in 1987/88. All consultants
      considered a high proportion of plans to be unacceptable, but agreement between
      the consultants was variable and some agreed with one another on very few plans.
      A single scorer used the weighted PAR (Peer Assessment Rating) index to assess
      the degree of departure from normal occlusion of both pre- and post-treatment
      models. Using accepted standards, only nine cases were greatly improved (PAR
      reduction > 70%) and the mean percentage reduction in PAR score was low.
      Consultant opinion on the appropriateness of treatment planning was not related
      to the outcome of orthodontic treatment.

PMID- 8258587
TI  - Displacement Rheometer: a method of measuring working time and setting time of
      elastic impression materials.
AB  - A new method of measuring both working time and setting time of elastomeric
      impression materials has been developed. A Displacement Rheometer was used to
      monitor the development of elasticity in setting elastomers. The results obtained
      with the Displacement Rheometer were compared to the results of the ISO test as
      well as those of the Controlled Stress Rheometer. Working time using the ISO
      method was calculated according to the standard method described in the
      specification, while for both the Controlled Stress Rheometer and the
      Displacement Rheometer working times were the times when initial elastic recovery
      was observed at 23 degrees C. With the Displacement Rheometer the setting time is
      the time when the mixed material reaches optimal elastic recovery at 37 degrees
      C. Statistical analysis with ANOVA showed that for five of the test materials
      there were no differences between the three methods. For three of the materials
      the working time determined by the ISO method was significantly longer than that
      determined by the other two methods. The advantages and disadvantages of each
      method are discussed and the Displacement Rheometer is recommended as a
      supplement to the standard specification method.

PMID- 8258588
TI  - Polyethylene fibre reinforced poly(methylmethacrylate)--water sorption and
      dimensional changes during immersion.
AB  - The reinforcement of acrylic denture base resin with high performance
      polyethylene fibre in chopped, woven and continuous parallel forms resulted in
      significant reductions in water sorption and dimensional changes during
      immersion. The dimensional changes during immersion mainly occur during the non
      steady state of the diffusion process.

PMID- 8258589
TI  - Radiometric and spectroradiometric comparison of power outputs of five visible
      light-curing units.
AB  - The spectral distributions of the radiation emitted by five visible range curing
      lights were measured spectroradiometrically. The light intensities in specific
      wavelength bands were evaluated by graphical integration. The results were then
      compared with the instantaneous readings of power density of all of the units as
      measured with a commercial curing radiometer. The data obtained by both
      techniques correlated well at narrower specific wavelengths (450-500 nm), which
      are assumed to be more effective for photopolymerization. This finding indicates
      that curing radiometer is sensitive to the desired wavelengths and may be an
      effective tool to quickly characterize the curing efficiency of dental
      photocuring sources in a clinical setting.

PMID- 8258590
TI  - The laminate technique: a critique of the Woolford review.

PMID- 8258591
TI  - Quality of life of adults with acute leukaemia.
AB  - The cause of acute leukaemia is unknown. Untreated, the disease is generally
      fatal after a few months. The therapeutic regimen is chemotherapy, and sometimes
      also bone marrow transplantation, and the aim is to cure the patient. Not only
      does the person live under pressure from a life-threatening disease with all the
      physiological complications that therapy can result in, the therapeutic regimen
      also involves a great psychological effect. The concept of quality of life (QOL)
      is individual for each person, as is his/her experience of the value of the
      contents of life. The principal aim of the study was to describe what QOL means
      to adults with acute leukaemia, not to describe the degree of QOL. The second aim
      was to give the concept of QOL a theoretical and empirical significance relevant
      to nursing care. Eight adults with diagnosed acute leukaemia detected in
      adulthood have been interviewed about their quality of life. The concept was
      given one superior dimension in all the interviews; positive attitude to life.
      Below the superior dimension were two further dimensions; interpersonal
      relationships and autonomy. Different qualities were given below these
      dimensions, viz. security, support, respect, information and conversation.

PMID- 8258592
TI  - To understand and alleviate suffering in a caring culture.
AB  - The purpose of this study is to help understand what suffering is, i.e. how
      patients and nurses describe suffering, and how suffering can be alleviated. The
      study has a descriptive-explorative design and its approach is phenomenological
      hermeneutical. The informant (research group) are 11 nurses (nurses, doctors,
      hospital theologians) and five patients in a social-psychiatric nursing unit,
      based on Christian ideology. The results of the study show that the 'what' of
      suffering is unclear. The nurses tend to describe more the 'why' of suffering,
      i.e. the reason for suffering. The what of suffering is pain, fear, despair, lack
      of strength. It is a form of lack of freedom and non-motion. It is a struggle
      between wanting and knowing, between guilt and responsibility. The form of
      suffering tends to mould the caring relation. To be touched in some way by
      another in a meeting can alleviate the deepest suffering. Compassion will always
      alleviate suffering.

PMID- 8258593
TI  - Disclosure of terminal prognoses in a general hospital: the nurse's view.
AB  - Some of the issues which nurses confront when they deal with the disclosure of
      terminal diagnoses and prognoses to patients are explored. In such circumstances,
      the nurse must respond to the competing demands of patients, relatives and
      medical staff. The paper examines the way in which a group of experienced staff
      nurses in a general hospital accounted for their activities during and after the
      disclosure of a lethal diagnosis. In particular, it explores the ways in which
      nurses are included or excluded from decision making about disclosure by medical
      staff.

PMID- 8258594
TI  - The role of the nurse providing therapeutic care for the suicidal patient.
AB  - In this study, nurses perceived that the implementation of special supervision is
      the most effective preventive method in the nursing care of suicidal patients,
      but they also expressed the view that special supervision is non-therapeutic. The
      results of these findings show that it is possible to provide nursing care in the
      prevention of further harm to the patient but that nurses may not necessarily be
      proficient in demonstrating the interpersonal caring skills essential for the
      development of a therapeutic relationship and hence patient recovery. This paper
      demonstrates there is now: (a) a need for special supervision as a preventive
      method when caring for the suicidal patient; (b) a need for a planned therapeutic
      programme of care during special supervision; (c) a need for the development of
      essential interpersonal and counselling skills and dimensions for effective
      therapeutic intervention and empathic nursing care; (d) a need to bridge the gulf
      between theory and practice by giving nurses the opportunity to practise those
      skills in the clinical setting under the supervision of an expert clinician; (e)
      a need for the patient to experience that nurses do care, i.e. experience
      empathy, during the complete therapeutic programme including the period of
      special supervision; and (f) a need for further research regarding the patient's
      perception of nursing care experienced following a failed suicidal attempt.

PMID- 8258595
TI  - Making risk meaningful: developing caring relationships with AIDS patients.
AB  - A qualitative study was conducted in order to understand how nurses cope with the
      risk of contagion while providing care to persons with AIDS (PWAs). Data were
      collected through in-depth interviews with 13 nurses who had cared for PWAs in an
      acute-care hospital in a western Canadian city. The data were analysed using the
      constant comparative methodology of grounded theory. The analysis revealed that
      caring for PWAs involved achieving a sense of control over uncertainty. One
      aspect of this process, making risk meaningful, centred on efforts to justify
      caring for PWAs in the face of risk. The purpose of this paper is to describe how
      nurses make risk meaningful. A sense of meaning was found to be related to three
      major factors: accepting the patient as a person who needs and deserves care,
      finding work enjoyable and worthwhile, and professional commitment to care for
      all patients. Attaining a sense of meaning led to a reappraisal of the risk
      situation as worthy of investment and provided the motivation to care for
      patients in spite of risk. The paper concludes with implications for practice and
      suggestions for further research.

PMID- 8258596
TI  - My death nearing its future: a Heideggerian hermeneutical analysis of the lived
      experience of persons with chronic illness.
AB  - Although over 50% of individuals over the age of 65 live with at least one
      chronic illness, little research has been conducted on the individual lived
      experience. For this phenomenological study, 12 individuals living with any long
      term illness participated in extended, non-structured, audio-recorded interviews.
      Resulting verbatim transcripts were analysed hermeneutically using Heideggerian
      phenomenology as the philosophical framework. The pattern 'my death nearing its
      future' emerged from this research. The understandings gained from these
      individual narratives provide important insight for all individuals interacting
      with persons living with chronic illness.

PMID- 8258597
TI  - Identifying and defining abuse of elderly people, as seen by witnesses.
AB  - The aim of this study was to analyse how Swedish district nurses defined and
      identified abuse of elderly people in practice. Twenty-one district nurses were
      interviewed by means of open-ended questions and their responses were analysed
      qualitatively. The main findings related to a central theme 'overriding the
      boundaries of a person's integrity/autonomy' and four categories; the act of
      abuse, the relationship between the abused person and the perpetrator, the
      experience of the abused person and the intention of the perpetrator. The
      reasoning of the district nurses focused on these issues. The district nurses
      included various aspects in the process of identifying abuse of elderly people
      and the findings demonstrate the complexity of the practitioner's situation. This
      seems logical since such abuse is complex and involves many aspects, which makes
      the diagnostic process difficult. The findings may be useful for nurses when they
      assess and intervene in abuse of elderly people. Thus, the significance of this
      study is mainly practical.

PMID- 8258598
TI  - Nursing and substance misuse: responding to the challenge.
AB  - The widespread use and misuse of alcohol, drug and other psychoactive substances
      are major health and social concerns that affect the lives of many. The social
      and health sequelae of psychoactive drugs and alcohol are preventable and
      manageable with minimal interventions. Nurses and other health workers can
      effectively respond to substance misuse problems and their existing generic
      skills can be easily adapted in working with substance misusers. This paper
      considers some of the issues such as the extent of the problem, attitudinal
      considerations, response to substance misusers and a brief outline of the role of
      the nurse. The urgent need for education and training in substance misuse and
      addictive behaviour for nurse practitioners is also addressed.

PMID- 8258599
TI  - A future perspective on patient/health education in Canada.
AB  - The current climate of health care redefinition and reform in Canada has prompted
      the need to review services and resources with a view to reducing costs,
      refocusing emphasis and maintaining the level of health care services of which
      Canadians are proud. This paper reviews the process of patient/health education
      using the PRECEDE model. This model encompasses the behavioural and non
      behavioural aspects of targeted health problems and their populations at risk,
      and three sets of strategic factors affecting educators and their clients. The
      paper examines the particular challenges implicit in each of the process
      components which are suggested by current trends and their implications for the
      future.

PMID- 8258600
TI  - The meaning of incontinence: a qualitative study of non-geriatric urinary
      incontinence sufferers.
AB  - The meaning of the problem for incontinence suffers is known to be a very
      significant influence on coping. The present study was based on in-depth
      qualitative interviews with 28 young or middle-aged women who suffered urinary
      incontinence. Analysis, aimed at discovering the meaning of their condition for
      the sufferers themselves, led to the following conclusions. Incontinence is
      taboo, meaning not only that it is a socially unacceptable topic of conversation
      (inhibiting the approach of suffers to health professionals), but also that it is
      difficult for suffers themselves to focus on and think about clearly. Sufferers
      can react with apathy, or may perpetually teeter on the edge of taking
      ameliorative action: rational ways of tackling the problem are often not
      followed. The problem is seen as one of personal control: incontinence is lack of
      a grip on bodily propriety. Sufferers may feel horribly unique, and also worry
      that the incontinence is their own fault. They fear a guilty association with
      despised groups. It is noteworthy that the maintenance of 'normality'--allowing
      the sufferer to claim that there is no problem and that she is not incontinent-
      may involve a great deal of work. Although there are indications of defensive
      denial in sufferers' reactions to the problem, an additional interpretation is
      that they are fighting to subordinate the problem in favour of other priorities.
      Implications for practice of each of these features of the meaning of
      incontinence are drawn out.

PMID- 8258601
TI  - The role of the clinical nurse co-ordinator in the provision of cost-effective
      orthopaedic services for elderly people.
AB  - Positions for nurses as coordinators and case managers have developed in response
      to demands for increased efficiency in the provision of hospital care. The
      Fractured Hip Management Programme in Western Sydney is one example of this
      development. The programme was introduced in response to mounting concern about
      the demands on hospital resources from elderly patients with hip fracture. A
      central feature of the programme is the pivotal role given to the nurse
      coordinator working within a multi-disciplinary team. This is not a new nursing
      role; rather it explicitly recognizes skills developed as part of the traditional
      nursing role. Evaluation of the programme found that patients received surgery
      sooner and spent less time in hospital, without adverse affects on outcome. The
      results show that recognition of the role of the nurse as patient advocate and
      care manager can lead to more cost-effective and higher-quality care.

PMID- 8258602
TI  - An international approach to master's-level preparation for clinical nurse
      specialists.
AB  - Nursing is seen as being increasingly a research-based profession with a
      developing knowledge base that demands a continuing programme of education. This
      is necessary to enable the practitioner to function with the level of expertise
      and skill required in today's health care systems. There have been repeated calls
      for and developments in the establishment of a higher-education approach to
      nursing, with degree courses for the advanced practitioner. It is also argued
      that in terms of the European perspective there are many commonalities in nursing
      and health care in Europe, and although cultural and national differences are
      important there can be advantages to nurses from different countries studying
      together. An example of a course which offers this European approach to higher
      education for nurses is described.

PMID- 8258603
TI  - Service evaluation: time to open both eyes.
AB  - This paper draws attention to issues raised by the present emphasis on service
      evaluation. It highlights in particular the limitation of many current models and
      argues the need to adopt a broad approach which takes account of the potentially
      disparate views of differing interest groups. The central tenets of a pluralistic
      model are presented and the benefits of such an approach are illustrated by
      reference to a recent evaluation of a respite care scheme for elderly people and
      their carers.

PMID- 8258604
TI  - Towards a better understanding of patients with irritable bowel syndrome.
AB  - This study was undertaken by sending a questionnaire to 148 people suffering from
      irritable bowel syndrome (IBS). The respondents all were members of the IBS
      Network, a national independent organization formed to help alleviate the
      suffering and distress of people diagnosed as having irritable bowel. They were
      asked about their symptoms, the medical tests they had undergone, how they felt
      about the treatment they received, and how IBS affected their lives. The study
      found that IBS affected all aspects of their lives: work, leisure, travel and
      relationships. Sufferers indicated that they felt they would have coped better if
      they had been provided with more information about IBS, its possible causes and
      treatment, and greater sensitivity from members of the medical profession in
      dealing with them.

PMID- 8258605
TI  - Core temperature measurement in adults: a literature review.
AB  - This paper provides a comprehensive review of the literature related to the
      clinical assessment of core body temperature in adults. It does not attempt to
      address temperature measurement in children. It considers temperature-taking
      instruments used in current practice, and predominantly investigates the use of
      the three main sites of rectum, mouth and axilla.

PMID- 8258606
TI  - An ethnographic study of nursing culture as an exploration for determining the
      existence of a system of ritual.
AB  - The idea that much of nursing is 'ritualized' activity which is harmful to
      patient care assumes that 'ritual' itself is unacceptable behaviour or practice.
      At a time when market forces are clearly influencing the delivery of care and, in
      turn, changes in nursing practice, it has become important both to clarify what
      'ritual' is and to determine its existence and 'form' within nursing. This study
      explored nursing culture for 'ritual' in a ward setting and used ethnography as
      both method and description. Rituals were found to exist in the working day of
      the nurses studied, but was not an indication that 'ritualized behaviour' is
      harmful to individualized patient care. There is a clear need, however, to
      determine specifically the difference between 'unsafe outdated practices' and
      ritual in a cultural 'sense'. This would ensure that what had to be relinquished
      would in no way jeopardize the future existence of nursing and nurses as socially
      cohesive groups with their own culture.

PMID- 8258607
TI  - The apparent desensitization of student nurses during their professional
      socialization: a cognitive perspective.
AB  - It is argued that the structures and processes of traditional patterns of pre
      registration nurse education in the United Kingdom led to an apparent and
      relative desensitization of student nurses to human need. The processes
      underpinning this apparent desensitization were those which promoted both a
      'compartmentalization' of concepts for theory and concepts for practice in the
      cognitions of student nurses and their habituation to examples of poor nursing
      practice. These processes are described and their nursing pedagogical
      implications are discussed. It is suggested that unless clinical learning
      environments are deliberately manipulated to foster the construction and
      utilization of 'appropriate' action schemata, the considerable opportunities
      offered by the implementation of Project 2000 to improve both nursing education
      and nursing practice could be wasted. It is further suggested that this
      deliberate manipulation should include nurse tutors teaching theory and practice
      in clinical areas if they are seriously concerned to render nursing care more
      intelligently responsive to human need.

PMID- 8258608
TI  - Participation of caregivers in elderly-patient hospital care: informal caregiver
      approach.
AB  - This preliminary study is part of an ongoing action research project in three
      different kinds of hospitals. Two wards in each hospital volunteered for the
      study. The purpose was to discover in which activities of daily living informal
      caregivers currently participate and to what extent. Participation of informal
      caregivers consisted of 17 activities. Elderly patients (n = 45) eligible for the
      study and informal caregivers (n = 147) completed a questionnaire. They were
      asked in which daily activities informal caregivers participate and how often,
      options ranging from daily to never. Responses of informal caregivers are
      reported in this paper. Results indicated that relatives and other significant
      others visited elderly hospital patients often; however, their participation in
      activities of daily living in hospitals was limited. Mostly they gave emotional
      support and helped the patient to drink, stand up/get into bed and sit.
      Implications for nursing are discussed.

PMID- 8258609
TI  - The relationship between nursing and higher education.
AB  - The paper explores the relationship between nursing and higher education with
      particular reference to the development of nursing degree programmes in the
      United Kingdom. The literature reveals that the contribution of nurse graduates
      to the profession has been examined to a limited extent: however, this has
      predominantly taken the form of follow-up studies, the majority of which were
      conducted in the 1980s. No empirically based work could be found which explores
      graduates' practice of nursing, the absence of which is significant in view of
      the more recent change in the conventional training programme, Project 2000, and
      the introduction of a number of 3-year nursing degree courses.

PMID- 8258610
TI  - The problem of motivating teaching staff in a complex amalgamation.
AB  - This paper addresses some of the problems brought about by the merger of a number
      of schools of nursing into a new complex amalgamation. A very real concern in the
      new colleges of nursing and midwifery in the United Kingdom is the effect of
      amalgamation on management systems and staff morale. The main focus of this paper
      is the motivation of staff during this time of change. There is currently a lack
      of security amongst staff and in many instances the personal job satisfaction of
      nurse teachers and managers of nurse education has been reduced, which has made
      the task of motivating staff difficult. Hence, two major theories of motivation
      and the implications of these theories for managers of nurse education are
      discussed. The criteria used for the selection of managers within the new
      colleges, leadership styles and organizational structures are reviewed. The
      amalgamations have brought about affiliation with higher-education institutions.
      Some problems associated with these mergers and the effects on the motivation of
      staff both within the higher-education institutions and the nursing colleges are
      outlined. Strategies for overcoming some of the problems are proposed including
      job enlargement, job enrichment, potential achievement rewards and the use of
      individual performance reviews which may be useful for assessing the ability of
      all staff, including managers, in the new amalgamations.

PMID- 8258611
TI  - Effect of multiple doses of nedocromil sodium given after allergen inhalation in
      asthma.
AB  - AIM: Twelve subjects with asthma took part in a placebo-controlled crossover
      study designed to investigate whether nedocromil sodium given after the
      occurrence of the early-phase asthmatic reaction to allergen has an effect on the
      late-phase response and the associated increase in airway responsiveness.
      METHODS: The treatments were administered four times at 4-hour intervals at a
      dose of 4 mg, with the first dose given 1 hour after the last allergen challenge.
      Changes in airway caliber were monitored for 15 hours after allergen exposure by
      measuring forced expiratory volume in 1 second hourly. Airway responsiveness to
      methacholine was determined 24 hours before and 24 hours after allergen
      challenge. RESULTS: Nedocromil sodium failed to reduce significantly the maximum
      late fall in forced expiratory volume in 1 second as compared with placebo but
      delayed its occurrence by 1.5 hours (p = 0.05). Nonspecific airway responsiveness
      to methacholine was similarly increased after allergen challenge when patients
      received nedocromil sodium and placebo. No unusual events were reported during
      the study period by any patient. These results indicate that nedocromil sodium is
      not able to interrupt the ongoing cascade of inflammatory events leading to the
      late-phase reaction and the associated increase in airway responsiveness.
      CONCLUSION: In allergic asthma, nedocromil can be used only as a preventive
      treatment.

PMID- 8258612
TI  - Characterization of grass group I allergens in timothy grass pollen.
AB  - Using Phl p V-depleted timothy grass pollen extract (Phleum pratense) as
      immunogen, we obtained a monoclonal antibody, QG 4, which recognized proteins of
      33, 35, and 37 kd as determined by Western blotting. The antibody cross-reacted
      with pollen proteins of other grass species in the molecular weight range of 30
      to 37 kd. By means of two-dimensional polyacrylamide gel electrophoresis blot of
      timothy grass pollen extract, we demonstrated at least seven protein spots: two
      of 37 kd with isoelectric points of 6.4 and 6.6; four of 35 kd with isoelectric
      points of 6.5, 6.8, 7.1, and 7.3; and one of 33 kd with an isoelectric point of
      8.5. These protein spots were also detected by patients' pooled serum.
      Microsequencing of the 20 N-terminal amino acid residues revealed structures with
      sequence identities up to 90% to the well-established allergen, Lol p I of
      ryegrass (Lolium perenne). Therefore we assume that the monoclonal antibody QG 4
      recognized the corresponding allergen Phl p I in timothy grass pollen.

PMID- 8258613
TI  - Airborne cat (Fel d I), dog (Can f I), and mite (Der I and Der II) allergen
      levels in the homes of Japan.
AB  - We measured the airborne and floor dust allergen levels of the cat (Fel d I), dog
      (Can f I), and mite (Der I and Der II) allergens in 13 houses. Airborne allergens
      were sampled with a low-noise air sampler for 5 to 7 days in the living rooms
      where the inhabitants were living as usual. The mean levels of airborne Fel d I
      and Can f I in houses with cats or dogs were 5960 and 2880 pg/m3, respectively,
      which were about 160 and 100 times higher than levels of airborne Der I. In floor
      dust the mean levels of Fel d I and Can f I were 322 and 236 micrograms/gm fine
      dust, respectively, which were 59 and 10 times higher than the levels of Der I.
      These results suggest that the airborne cat and dog allergens might be important
      sources of allergens for persons who live in a house with those animals, because
      the absolute allergen levels in both the air and dust are significantly higher
      than those of mite.

PMID- 8258614
TI  - Atopic profile of inner-city asthma with a comparative analysis on the cockroach
      sensitive and ragweed-sensitive subgroups.
AB  - BACKGROUND: Inner-city asthma is well known for its high risk of mortality. To
      better understand urban asthma, we examined clinical characteristics and
      aeroallergen sensitivities of 592 of 680 consecutive urban Chicago residents with
      asthma. METHODS: A total of 227 male and 453 female subjects who met the criteria
      for the study were registered. A comprehensive clinical evaluation was followed
      by allergy skin testing (prick and intradermal testing) with 10 groupings (5
      indoor and 5 outdoor) of common aeroallergens. Serum total IgE and selective
      antigen-specific IgE levels, including cockroach-specific IgE, were routinely
      measured. A total of 592 (196 male and 396 female) subjects with an average age
      of 35 years were skin tested. The average duration of asthma was 12.6 years, and
      31% of the population was receiving corticosteroids. RESULTS: Aeroallergen
      sensitivity was noted in 85%, and 94 subjects (15%) were nonallergic. House dust
      sensitivity (76%) was most prevalent, distantly followed by sensitivity to
      cockroach (48%), ragweed (45%), other weeds (42%), cat (40%), and dust mite
      (24%). The average number of aeroallergen sensitivities detected was 4 of 10
      groupings of both indoor and outdoor allergens. Twenty percent of subjects were
      allergic to only indoor allergens, whereas 4% were allergic to outdoor allergens
      only. Serum IgE was 245 +/- 17.3 IU/ml (geometric mean+SEM), and 74% of 444 serum
      samples showed IgE antibody levels greater than or equal to 100 IU/ml. A
      cockroach-sensitive subgroup (283 subjects) had longer duration of asthma (p <
      0.0001) and fewer additional aeroallergen sensitivities (p < 0.0001) than the
      ragweed-sensitive subgroup (264 subjects). CONCLUSION: The results indicate that
      a great majority (85%) of inner-city Chicago residents with asthma have atopic
      asthma, as demonstrated by highly elevated IgE levels and multiple aeroallergen
      sensitivities. Sensitivity to indoor allergens is more prevalent than sensitivity
      to outdoor allergens. The subjects with cockroach-sensitive asthma appear to be a
      distinctive subgroup characterized by chronicity and elevated serum IgE antibody
      levels with fewer aeroallergen skin test sensitivities.

PMID- 8258615
TI  - Intranasal flunisolide spray as an adjunct to oral antibiotic therapy for
      sinusitis.
AB  - BACKGROUND: The diagnosis of sinusitis is difficult and there are few controlled
      studies of customary therapies. In particular, the possible role of topical
      intranasal steroid as an adjunct to antibiotic treatment has not been evaluated.
      METHODS: The study was a multicenter, double-blind, randomized, parallel trial in
      which patients aged 14 years or older were recruited from allergy practices. All
      patients had maxillary sinusitis documented by radiographs. Treatment consisted
      of amoxicillin/clavulanate potassium 500 mg combined with nasal spray of either
      100 micrograms flunisolide or placebo to each nostril three times a day for 3
      weeks (phase I) followed by administration of flunisolide or placebo nasal spray
      alone three times a day for 4 weeks (phase II). RESULTS: Clinical symptoms and
      signs decreased significantly in both treatment groups during phase I (p < 0.01).
      There was a trend to greater improvement in the patients treated with
      flunisolide, but only the decrease in turbinate swelling/obstruction was
      statistically significant at the end of phase I when compared with placebo (p =
      0.041). Patients' global assessment of overall effectiveness of treatment was
      higher for flunisolide than placebo after phase I (p = 0.007) and after phase II
      (p = 0.08). Maxillary sinus radiographs showed improvement in both treatment
      groups during phase I (p < 0.004) with somewhat greater regression of abnormal
      findings in patients treated with flunisolide after phase II (p = 0.066).
      However, 80% of radiographs were still abnormal at the end of phase I. All types
      of inflammatory cells were significantly decreased in nasal cytograms in patients
      treated with flunisolide in comparison with those treated with placebo. Flare-up
      of sinusitis during phase II occurred in 26% of with those treated with placebo.
      Flare-up of sinusitis during phase II occurred in 26% of patients treated with
      flunisolide and 35% of those treated with placebo and tended to be more severe in
      the latter, although these differences were not statistically significant.
      Adverse events, mainly gastrointestinal symptoms and headache, were similar in
      both groups and more frequent in phase I than in phase II, (42 vs 15 patients);
      these side effects were probably due to the antibiotic. CONCLUSION: The addition
      of flunisolide topical nasal spray as an adjunct to antibiotic therapy was most
      effective in global evaluations, tended to improve symptoms, to decrease
      inflammatory cells in nasal cytograms, to normalize ultrasound scans, and to aid
      regression of radiographic abnormalities compared with placebo spray.

PMID- 8258616
TI  - Chronic sinusitis among pediatric patients with chronic respiratory complaints.
AB  - We examined the prevalence of chronic sinusitis among children who presented to
      allergy clinics with chronic (> or = 3 months) respiratory symptoms. Ninety-one
      patients, ranging from 2 to 17 years of age with 62% male and 72% white,
      completed the study. Fifty-nine percent of patients had positive skin test
      results, and 25.3% had chronic asthma. Paranasal sinuses were examined by coronal
      sinus computed tomographic scan. Sixty-three percent (58 to 91) had chronic
      sinusitis, 5.5% (5 of 91) had concha bullosa, 1% (1 of 91) had foreign body, and
      19% (19 of 91) had deviated nasal septums. Among symptoms of sneezing, nasal
      congestion, postnasal drip, coughing, wheezing, rhinorrhea, and headache, no
      single symptom was an acceptable predictor of abnormality on computed tomographic
      scan examinations. Combining the symptoms of moderate to severe rhinorrhea and
      cough with minimum sneezing had a specificity of 95% and a sensitivity of 38% in
      predicting the presence of chronic sinusitis. Allergic rhinitis (p = 0.27), mild
      deviated nasal septum (p = 0.11), unobstructive concha bullosa (p = 0.13), and
      passive exposure to cigarette smoke (p = 0.53) were not risk factors associated
      with sinus abnormalities. Age (r = 0.30, p = 0.004) in pediatric patients with
      chronic respiratory symptoms was the single risk factor significantly associated
      with abnormalities on sinus computed tomographic scan. Seventy-three percent of
      children 2 to 6 years of age, 74% of children 6 to 10 years of age, and 38% of
      children older than 10 had chronic sinusitis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258617
TI  - Duration of venom immunotherapy: relationship to the severity of symptoms of
      initial insect sting anaphylaxis.
AB  - BACKGROUND: This study assessed the postulate that the adequate duration of venom
      immunotherapy (VIT) is related to the severity of the initial sting anaphylactic
      symptoms. METHODS: Data were collected from patients with venom allergy who had
      sting anaphylaxis and subsequent positive venom skin test results, received
      maintenance VIT, and had field re-stings after cessation of VIT. There were 217
      re-stings in 113 patients with 15 systemic reactions in 10 patients (a re-sting
      reaction rate of 9% per sting and 7% per patient). RESULTS: Re-sting reactions
      occurred in 1 of 25 patients with initial mild anaphylaxis (4%), 2 of 41 patients
      with moderate reactions (5%), and 7 of 47 patients with initial severe symptoms
      (15%). The results were not influenced by the duration of VIT or the interval
      between cessation of VIT and the re-sting. Eighteen patients who converted to
      negative skin test reactions had no reactions when re-stung. CONCLUSIONS: These
      results suggest a relationship between the severity of anaphylaxis and subsequent
      duration of VIT. Two to three years is sufficient for patients who had mild to
      moderate anaphylaxis. Longer duration of therapy is advisable for patients who
      had severe symptoms and continue to have positive venom skin test results.

PMID- 8258618
TI  - Identification and characterization of a 30 kd major allergen from Parapenaeus
      fissurus.
AB  - The allergenic components of the shrimp (Parapenaeus fissurus) were identified by
      immunoblotting with sera from 10 allergic patients. Six components, ranging in
      molecular weight from about 86 to 39 kd, showed IgE-binding activity and were
      identified as allergens of the shrimp. The component with a molecular weight of
      about 39 kd showed the highest frequency of IgE binding (70%) and was considered
      to be one of its major allergens. Two monoclonal antibodies against this 39 kd
      component were generated, and their antigenic cross-reactivity with five
      different kinds of seafood, shrimp, crab, cuttlefish, oyster, and pomfret was
      analyzed. Monoclonal antibody 1-6-10B reacted with the 39 kd component from
      shrimp only, but monoclonal antibody 2-7-1E also reacted with the 39 kd component
      from crab. By extraction with 0.5% sodium dodecylsulfate and ethanol
      precipitation, a highly purified shrimp 39 kd component was obtained. In two
      dimensional gel electrophoresis six isoforms of this purified 39 kd component,
      with isoelectric point values from 5.1 to 5.6, were identified. No marked
      difference was observed when the amino acid composition of this purified 39 kd
      allergen was compared with those of serum albumin from different animals. They
      all contain a high proportion of acidic amino acids. There was also a 62% to 83%
      sequence homology among three different pairs of peptide fragments of purified 39
      kd components of shrimp and crab. In conclusion, a 39 kd major allergen from the
      shrimp has been identified and characterized in the present study. According to
      the suggestions of the International Union of Immunological Societies, this
      allergen is designated as Par f I.

PMID- 8258619
TI  - Anaphylaxis after ingestion of beignets contaminated with Dermatophagoides
      farinae.
AB  - A 48-year-old man was evaluated for anaphylaxis associated with ingestion of
      beignets prepared from a commercial mix. Microscopic examination of the patient's
      beignet mix revealed live Dermatophagoides farinae. Another unopened box from the
      same source was not infested. Skin test results to aeroallergens and foods,
      including all beignet mix ingredients, were positive only to D. farinae and D.
      pteronyssinus extracts. Skin prick test results to an infested mix extract (1:5
      wt/vol) were also positive, but no reaction was observed with noninfested mix
      extract. ELISA inhibition studies demonstrated significant inhibition of the
      patient's serum binding to D. farinae strips by infected mix extract. Parallel
      inhibition curves were produced by the infested mix extract and a commercial D.
      farinae extract. Noninfested mix extract showed no inhibition. RAST analysis with
      beignet mix discs showed significant binding of the patient's serum IgE to
      infested mix discs but not to noninfested mix discs. RAST inhibition studies
      revealed more than 86% inhibition of binding of the patient's IgE to infested mix
      discs by infested mix extract and D. farinae extract. No inhibition was observed
      with noninfested mix or 5% fetal calf serum-phosphate-buffered saline. We
      conclude that the allergen to which the patient reacted was most likely D.
      farinae and that ingestion of D. farinae may cause anaphylaxis in sensitive
      persons.

PMID- 8258620
TI  - The effect of local hyperthermia on allergen-induced nasal congestion and
      mediator release.
AB  - BACKGROUND: Local hyperthermia reduces mast cell degranulation, the severity of
      acute lung injury, and exercise-induced asthma and decreases symptoms of
      rhinitis. We have investigated the effect of local hyperthermia on mast cell
      degranulation and symptom generation in allergic rhinitis to assess its effect
      and mechanism of action within the nose. METHODS: In a randomized, double-blind,
      placebo-controlled, crossover study, 10 subjects with rhinitis were treated for
      30 minutes with local hyperthermia or placebo, which was followed 30 minutes
      later by nasal allergen challenge. During the first two visits nasal lavages were
      performed to assess vascular leakage and mediator release. During the last two
      visits nasal airway resistance, the number of sneezes, and mucus secretion were
      monitored. RESULTS: Local hyperthermia significantly reduced both nasal airway
      resistance (p < 0.05) and vascular leakage (p < 0.02) but had no significant
      effect on the number of sneezes, on mucus secretion, or on tryptase release.
      CONCLUSION: Local hyperthermia reduces allergen-provoked nasal blockage and
      vascular leakage but has no effect on sneezing, rhinorrhea, or tryptase release.
      Nasal blockage occurs predominantly via newly formed lipid mediators and kinins,
      whereas sneezing and rhinorrhea occur predominantly via preformed mediators. We
      propose that local hyperthermia inhibits newly formed mediator production or
      release or reduces the sensitivity of the vasculature to inflammatory mediators
      in general. Further investigation into the mechanisms and potential uses of local
      hyperthermia is warranted.

PMID- 8258621
TI  - Airway macrophages from patients with asthma do not proliferate.
AB  - BACKGROUND: Macrophages are involved in asthma, but their pulmonary turnover is
      unknown. We compared the ability of bronchoalveolar lavage (BAL) and bronchial
      macrophages to proliferate in normal subjects and patients with asthma. METHODS:
      BAL cells from eight patients with asthma and eight normal volunteers were
      separated with a discontinuous Percoll gradient (Pharmacia Fine Chemicals,
      Uppsala, Sweden). In a first experiment, nuclei of each alveolar macrophage (AM)
      fraction, stained with propidium iodide, were analyzed for DNA content with a
      flow cytometer, and the proportions of cells in the G0/G1, S, and G2 + M phases
      were determined. In a second experiment, expression of Ki-67-related antigen was
      sought on AMs by immunocytochemistry. Macrophages from 10 patients with asthma
      and 10 normal volunteers were studied in biopsy specimens by means of
      immunohistochemistry with a panmacrophage monoclonal antibody (HAM-56) and a
      monoclonal antibody against proliferating cell nuclear antigen. RESULTS: The
      proportions of BAL AMs in the different phases of the cell cycle were similar in
      normal subjects and patients with asthma for all fractions, and the percentage of
      cells in S and G2 +/- M phases ranged from 7.3% to 11.3%. Under 1% of BAL AMs
      expressed Ki-67-related antigen. None of the macrophages present in the biopsy
      specimens expressed proliferating cell nuclear antigen. CONCLUSIONS: This study
      does not indicate that an important source of airway macrophages is local
      proliferation.

PMID- 8258622
TI  - Interleukin-6 and interleukin-1 alpha production is associated with antigen
      induced late nasal response.
AB  - BACKGROUND: Cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1 alpha, IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) are
      able to potentiate allergic inflammation and seem to be implicated in the
      development of the late allergic reaction. METHODS: To study the time course of
      cytokine production, sequential lavages were performed after nasal allergen
      challenge. Thirteen patients with allergic rhinitis and four healthy subjects
      were exposed to grass pollen (n = 6 and n = 2, respectively) or dust mite
      allergen (n = 7 and n = 2, respectively). RESULTS: Among the patients with
      allergic rhinitis, a single early response (single responders) developed in four,
      eight exhibited a dual response (dual responders) and one patient as well as the
      four healthy subjects did not respond. In addition to the measurement of IL-1
      alpha, IL-6, TNF-alpha and GM-CSF concentrations by ELISA, the release of
      histamine, tryptase, and eosinophil cationic protein was also evaluated by
      radioimmunoassay performed on nasal lavage fluids. Concerning mediator levels in
      nasal lavage fluid, neither histamine release nor cytokine elevation were noted
      in healthy subjects. As previously described, histamine, tryptase and eosinophil
      cationic protein were released in single and dual responders. Concerning
      cytokines, TNF-alpha was undetectable in the majority of nasal lavages and an
      increase in GM-CSF concentration was occasionally observed whatever the type of
      response. In contrast, an increase in IL-1 alpha and IL-6 levels was observed for
      dual responders during the early period (12.6 +/- 3 and 9.2 +/- 2 pg/ml,
      respectively; p < 0.01 in both cases) and at a higher level during the late
      period (14.5 +/- 4, p not significant and 16.7 +/- 8 pg/ml, respectively; p <
      0.01) when compared with baseline values (7.2 +/- 2.2 and 2 +/- 0.7 pg/ml,
      respectively). For single responders IL-1 alpha and IL-6 secretion was detected
      mainly during the early period. CONCLUSION: These data suggest a role for IL-1
      alpha in the induction and perennisation of the inflammatory reaction in allergic
      rhinitis, whereas the role of IL-6 remains to be investigated.

PMID- 8258624
TI  - Cytokine profile of viral and autoimmune chronic active hepatitis.
AB  - BACKGROUND: Patients with hepatitis have multiple immunologic abnormalities,
      which may be related to cytokine production. METHODS: We examined the in vitro
      production of interleukins (IL-2, IL-4, IL-6), tumor necrosis factor-alpha (TNF
      alpha), and interferon-gamma (IFN-gamma) in purified peripheral blood mononuclear
      cells (PBMCs) of patients with hepatitis B virus positive (HBV), acute viral
      hepatitis (A-HBV), HBV + chronic active hepatitis (HBV-CAH), and autoimmune-type
      chronic active hepatitis (AI-ACH). RESULTS: IFN-gamma and TNF-alpha production
      were characteristically higher in patients with A-HBV than in healthy control
      subjects (p < 0.001). However, patients with AI-CAH produced highly elevated
      levels of IL-4 and IL-6 compared with patients with A-HBV and HBV-CAH and healthy
      control subjects. The cytokine profile (PBMC-induced IL-2, IL-4, IL-6, IFN-gamma,
      and TNF-alpha production) is different in A-HBV, HBV-CAH, and AI-CAH disease. The
      increased cytokine secretion (IFN-gamma and TNF-alpha in A-HBV and IL-4 and IL-6
      in AI-CAH) could reflect altered relative frequencies of different cell
      phenotypes in these diseases. CONCLUSIONS: Specific cytokine production may be
      important in the pathophysiology associated with diverse inflammatory states in
      patients with hepatitis.

PMID- 8258623
TI  - Isotype-specific regulation of human lymphocyte production of immunoglobulins by
      sustained exposure to vasoactive intestinal peptide.
AB  - Exposure of lymphocytes to nanomolar to micromolar concentrations of vasoactive
      intestinal peptide (VIP) for 1 to 3 days only modestly suppressed or enhanced the
      production of IgA and IgM, but not IgG. The effects of twice daily additions of
      10(-12) to 10(-7) mol/L VIP for up to 18 days on pokeweed mitogen-stimulated
      peripheral blood mononuclear cells (PBMCs) from normal human subjects was
      examined by quantifying the production of IgG, IgM, and IgA. The maximum
      suppression of IgG by 10(-9) mol/L VIP was 79% +/- 33% (mean +/- SD) (range, 41%
      to 97%; p < 0.015) on day 9 and 84% +/- 1% (range, 74% to 96%; p < 0.0001) on day
      14 and was significant at 6 x 10(-10) to 4 x 10(-9) mol/L VIP. Suppression of IgM
      production by 10(-9) mol/L VIP was significant and was observed first on day 5
      and persisted through day 14. VIP did not alter IgA production or affect the
      proliferation or viability of PBMCs. The production of IgE by interleukin-4
      stimulated PBMCs was enhanced consistently in two subjects but not in two other
      subjects. The duration of exposure to nanomolar concentrations of VIP is thus a
      critical determinant of its immunoregulatory effect, as manifested by late
      suppression of production of IgG and IgM and concurrent enhancement of production
      of IgE in some subjects.

PMID- 8258625
TI  - Food protein-induced enterocolitis to casein hydrolysate formulas.

PMID- 8258626
TI  - A proposed screen for evaluating low-molecular-weight chemicals as potential
      respiratory allergens.
AB  - Allergic asthma can result when reactive low-molecular-weight chemicals (LMWCs)
      haptenate carrier proteins to form immunogenic conjugates, which then induce
      specific allergic antibodies. As part of an overall assessment process for
      evaluating the allergenic potential of LMWCs, an in vitro test for detecting the
      covalent derivatization of proteins by LMWCs was developed. In the assay,
      globulin-free serum albumins were incubated with increasing concentrations of a
      given LMWC and the mixtures separated via reversed-phase high-performance liquid
      chromatography (HPLC). Derivatization was monitored by shifts in the retention
      time of native versus modified protein. Retention time shifts were seen for most
      haptens when incubated with human serum albumin at a 50:1 (hapten:protein)
      starting molar ratio. Some haptens changed the retention time of the protein at a
      5:1 initial ratio. Almost all chemicals that non-covalently bind to proteins did
      not change the protein retention time, even when incubated at 1500:1 molar
      ratios. The screen correctly identified 12/14 known human allergenic haptens and
      23/24 non-allergenic LMWCs. It cannot detect sensitizers which must be
      metabolized into reactive haptens. This screen can be incorporated into an
      overall risk assessment approach for evaluating chemicals as respiratory
      allergens.

PMID- 8258627
TI  - An attempt to improve the SOS chromotest responses.
AB  - The SOS Chromotest was carried out on leachates of ten industrial wastes with the
      standard procedure and a miniaturized version with microplates. The two methods
      gave identical results in nine samples (eight negative and one positive). A
      simple additional manipulation is described for the identification of the false
      positive response that is frequently observed with complex mixtures. It involves
      challenging the SOS Chromotest bacteria with samples (having previously shown a
      positive genotoxic response) just before the enzymatic activities (i.e. beta
      galactosidase and alkaline phosphatase) are estimated colorimetrically. This
      additional step eliminates discrepancies between the results for the standard and
      the miniaturized procedures.

PMID- 8258628
TI  - Decreasing 203Hg retention by intraperitoneal treatment with monoalkyl esters of
      meso-2,3-dimercaptosuccinic acid in rats.
AB  - The effect of nine monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) on
      203Hg retention after a single i.p. dose was evaluated in 6-7 week-old female
      albino rats. The monoesters were the monomethyl (MMDMS), monoethyl (MEDMS), mono
      n-propyl (Mn-PDMS), monoisopropyl (Mi-PDMS), mono-n-butyl (Mn-BDMS), monoisobutyl
      (Mi-BDMS), mono-n-amyl (Mn-ADMS), monoisoamyl (Mi-ADMS) and mono-n-hexyl (Mn
      HDMS). Dimercaptosuccinic acid or one of the monoesters were administered at a
      dose of 0.25 mmol kg-1 body wt. twice, i.e. 30 min and 24 h after 203Hg
      administration. The whole body (WB) radioactivity was determined on the 2nd, 4th
      and 6th days. The radioactivity in the carcass (C) (whole body without the
      gastrointestinal tract), liver (L), both kidneys (K) and brain (B) was determined
      6 days after 203Hg administration. All treated animals had a significantly lower
      body burden of mercury than the controls. The reduction of 203Hg retention in WB
      and other body compartments was higher in animals treated with monoesters than in
      rats treated with DMSA. The relative effectiveness of the monoesters was
      dependent on the nature of the alkyl groups, the efficiency being higher in
      higher analogues. Maximum activity was attained with the C5 (Mn-ADMS, Mi-ADMS)
      and C6 (Mn-HDMS) esters. These chelators reduced WB, C, L, K and B mercury
      retention by 90, 89, 76, 93 and 80%, respectively. Iso derivatives were more
      efficient than the normal isomers (Mi-PDMS > Mn-PDMS; Mi-BDMS > Mn-BDMS; Mi-ADMS
      > Mn-ADMS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258629
TI  - Leakage of mitochondrial and cytosolic GOT in isolated rat hepatocytes exposed to
      halothane: an immunohistochemical study.
AB  - The leakage of mitochondrial (m-) and cytosolic (s-) aspartate aminotransferases
      (glutamic-oxaloacetic transaminase: GOT) from isolated hepatocytes exposed to
      halothane was investigated immunohistochemically. In control isolated
      hepatocytes, a large number of cells were immunopositive (m-GOT, 85%; s-GOT,
      98.5%) at various intensities. Reaction products of m-GOT-immunohistochemistry (m
      GOT-I) were seen exclusively in mitochondria, while those of s-GOT (s-GOT-I) were
      seen in the cytoplasm. When treated with low concentrations of halothane (up to
      0.75%), the number of strongly m-GOT-I-immunopositive cells was reduced to half,
      while that of s-GOT-I showed no noticeable change. The number of m-GOT-I
      immunonegative cells showed a negligible increase, while that of s-GOT-I
      increased gradually. At higher concentrations of halothane (1% or more), strongly
      immunopositive cells in both m- and s-GOT-I almost disappeared, while
      immunonegative cell numbers predominantly increased. This study showed that the
      isolated hepatocyte system was not homogeneous with regard to the quantity of GOT
      isozymes, and that halothane could induce the leakage of these isozymes from
      hepatocytes, along with inducing ultrastructural abnormalities, even at the
      lowest concentration used (0.5%). Furthermore, the data appear to indicate that
      the sensitivity of isolated hepatocytes to halothane is dependent on the nature
      of the hepatocyte itself and on the nature of both types of GOT isozymes.

PMID- 8258630
TI  - Studies on the delayed neuropathic and anticholinesterase potential of quinalphos
      (diethyl 2-quinoxalyl phosphorothionate) in hens.
AB  - Incidence of numerous human poisonings by quinalphos (Ekalux, Bayrusil) in
      agricultural areas near Belgrade initiated this study on the ability of the
      compound to inhibit hen brain neuropathy target esterase, acetylcholinesterase
      and plasma butyrylcholinesterase in vivo. Hens were treated with a single oral
      dose ranging from 25 to 600 mg kg-1 quinalphos (LD50 = 72 mg kg-1) or 500 mg kg-1
      triorthocresyl phosphate (positive control), sacrificed 24-96 h later for enzyme
      assays and monitored for 25 days for evaluation of walking impairments. High
      inhibition (> 80%) of both cholinesterases was obtained with 25 and 50 mg kg-1
      quinalphos. Doses of 200 and 600 mg kg-1 of the agent inhibited up to 23 and 28%
      of hen brain neuropathy target esterase activity, respectively. Clinical signs of
      neuropathy were not seen. Quinalphos was slowly absorbed from the
      gastrointestinal tract, as indicated by the severity of the cholinergic symptoms
      and the inhibition of neuropathy target esterase, which reached its maximum 72
      and 96 h after poisoning. The results suggest that quinalphos, at doses tested,
      has no ability to cause delayed neuropathy in hens without showing signs of
      severe cholinergic intoxication.

PMID- 8258631
TI  - Induction of chromosomal aberrations and sister chromatid exchange in vivo and in
      vitro by the insecticide cypermethrin.
AB  - The induction of chromosomal aberrations and sister chromatid exchange in vivo in
      mouse spleen and bone marrow as well as in vitro in cultured mouse spleen cells
      by the insecticide 'Cypermethrin' (cis-trans 1:1) was investigated. The
      percentage of chromosomal aberrations in the spleen and in the bone marrow as
      almost the same and reached its maximum 6 h following i.p. injection. The
      aberrations induced were chromatid and chromosome gaps, fragments and
      tetraploidy. The insecticide caused a significant and dose-dependent increase in
      the frequency of sister chromatid exchanges (SCEs) in mouse bone-marrow cells: it
      reached 11.12 +/- 0.05 per cell after treatment with Cypermethrin at 300 mg kg-1
      body wt. compared with 3.7 +/- 0.14 per cell and 4.4 +/- 0.26 per cell in the
      solvent and control, respectively. The percentage of viable cells in mouse spleen
      cell cultures reached 87.4% and 99.9% relative to the control after treatment of
      the cell cultures with 10(-3) and 10(-7) Cypermethrin, respectively. All the
      tested concentrations of Cypermethrin (0.25-400 micrograms ml-1) induced a high
      percentage of metaphases with chromosomal aberrations after 4 h of treatment. The
      mean frequency of SCEs per cell reached 15.1 +/- 0.05 after treatment with
      Cypermethrin at 4.00 micrograms ml-1 compared with 8.6 +/- 0.23 and 5.9 +/- 0.39
      in the solvent and control, respectively. The results indicate that Cypermethrin
      is genotoxic in mouse spleen and bone marrow as well as in cultured mouse spleen
      cells.

PMID- 8258632
TI  - The toxicity of seed extracts and their fractions from Lupinus angustifolius L.
      and Lupinus albus L.
AB  - Seed extracts obtained from Lupinus albus and Lupinus angustifolius by treatment
      with 48% ethanol contained ca. 10% alkaloids (on a dry weight basis) and were non
      toxic. Their acute toxicity (LD50) in the mouse is > 4000 mg kg-1 body wt. After
      fractionation, the extract from L. angustifolius seeds afforded several fractions
      with differing toxicities (LD50 750-4000 mg kg-1 body wt.). None of the fractions
      tested in vitro were toxic. The results obtained showed that, in spite of the
      alkaloids, other low-molecular-weight constituents present significantly modified
      the toxicity of the lupin extracts.

PMID- 8258633
TI  - Dominant lethal study of sulfur mustard in male and female rats.
AB  - Sulfur mustard (HD) (bis(2-chloroethyl)sulfide) is a strong alkylating agent with
      known mutagenic and suspected carcinogenic properties, but occupational health
      standards have not been established. The purpose of this study was to determine
      the dominant lethal effect in male and female rats dosed orally with HD, for
      which currently available data are ambiguous. Sprague-Dawley rats of each sex, 6
      7 weeks old, were orally administered 0, 0.08, 0.20 or 0.50 mg kg-1 HD 5 days a
      week for 10 weeks, after which dominant lethal studies were conducted during the
      post-exposure period. The studies were conducted in two phases: a female dominant
      lethal phase in which treated or untreated males were mated with treated females
      and their fetuses were evaluated 14 days after copulation; and a male dominant
      lethal phase in which treated males cohabited with untreated females for 5 days
      and fetuses were evaluated 14 days after the mid-point of the week of
      cohabitation, for each of 10 weeks. In addition, motility, population size and
      morphology were measured in sperm obtained from the cauda epididymis. Parental
      growth rates were reduced in both sexes treated with the high level of HD. Female
      dominant lethal effects were not observed, although significant male dominant
      lethal effects were observed in HD-exposed male rats mated to untreated females
      at 2 and 3 weeks' post-exposure. These effects, which included increases of early
      fetal resorptions and preimplantation losses and decrease in total live embryo
      implants, were most consistently observed at a dose of 0.50 mg kg-1. A
      significant P(P < 0.05) increase in the percentage of abnormal sperm was detected
      in males exposed to 0.50 mg kg-1 HD. The timing of dominant lethal effects is
      consistent with an effect during the post-meiotic stages of spermatogenesis,
      possibly involving the generally sensitive spermatids.

PMID- 8258634
TI  - Effects of high exposure concentrations of inhaled low-toxicity dust on pulmonary
      function in guinea pigs.
AB  - The acute pulmonary function response to graded levels of a low toxicity dust was
      studied in guinea pigs. Four groups of five male guinea pigs each were exposed to
      mean concentrations of 0, 0.25, 1.01 and 5.39 mg Foundry Hill Clay l-1 air with
      mass median aerodynamic diameters of 2.6, 4.6 and 6.7 microns, respectively.
      There was a 15-min pre-exposure period to clean air, a 1-h exposure to the test
      atmosphere and then a 1-h recovery period with exposure to clean air.
      Concentration-related changes, compared to the pre-exposure period, occurred with
      a rapid onset in a number of parameters. Generally, the severity of observed
      effects increased with exposure time and, therefore, with inhaled dose.
      Statistically significant changes (P < 0.05) were observed in tidal volume,
      dynamic compliance, dynamic resistance, flow, pressure and minute volume during
      the last 15 min of exposure. The observed changes were consistent with acute
      bronchoconstriction. These effects reversed rapidly and there were no significant
      changes 1 h post-exposure. These results suggest that adverse physiological
      responses of short duration can occur when animals are exposed via inhalation to
      low-toxicity materials in the concentration range 0.25-5 mg l-1.

PMID- 8258635
TI  - Kidney function in male and female rats chronically exposed to potassium
      dichromate.
AB  - Male and female Wistar rats were given 25 mg l-1 chromium (as potassium
      dichromate) in drinking water for 6 months. Lactate dehydrogenase, lysozyme,
      total proteins, N-acetyl-beta-D-glucosaminidase, albumin and beta 2-microglobulin
      (beta 2-m) were measured in 24-h urine after 3 and 6 months of exposure. Body and
      kidney weight and chromium excretion were also examined. Except for the chromium
      excretion, no statistically significant changes were observed in the exposed male
      rats. In female rats there were significant increases in the urinary excretion of
      albumin after 3 and 6 months of exposure and the urinary excretion of beta 2-m
      after 3 months of exposure.

PMID- 8258636
TI  - Benomyl.

PMID- 8258637
TI  - Affinity methods with lectins: a tool to identify canine alkaline phosphatase
      isoenzymes.
AB  - Affinity methods were used to characterize selective interactions of alkaline
      phosphatase (ALP) isoenzymes from different dog tissues with lectins. Specific
      lectins were used to identify liver, intestinal and steroid-induced ALP
      isoenzymes in serum from dogs with Cushing syndrome or steroid-treated dogs. For
      the first approach, 12 lectins were assayed by affinity dots. Selective
      interactions were found among wheat germ agglutinin (WGA), jacalin, con A
      (concanavalin A) and Helix pomatia agglutinin (HPA) and several ALP-containing
      samples. These four reactive lectins were assayed by line electrophoresis with
      lectins in holes. A strong reactivity of con A with all isoenzymes was found,
      although the patterns were different. WGA interacted with intestinal, bone marrow
      extracts and Cushing syndrome serum. Jacalin changed the electrophoretic patterns
      of intestinal and liver ALP, and Cushing serum. Finally, by crossed
      electrophoresis with lectins in gels, it was possible to distinguish among
      hepatic or intestinal ALPs and the steroid-induced isoenzyme in serum. Affinity
      electrophoresis with lectins provided a clear separation and identification of
      the different dog ALP isoenzymes.

PMID- 8258638
TI  - A flow-through microsampling device applied to an ion-exchange chromatography
      system.
AB  - A flow-through microsampling device that can be inserted in the column elution
      flow line of a chromatographic system has been developed. A sample drop (volume
      2.2 nl) is ejected when a voltage pulse is applied to a piezo-electric
      transducer. The drops can be ejected with up to 70 Hz frequency, giving a sample
      flow range of 0-9 microliters/min. Samples were collected on a moving agarose
      surface during elution of freshly prepared human serum. The precipitate pattern
      obtained after immunoelectrophoresis is similar to what would be obtained in a
      fused rocket electrophoresis of multiple samples from a fraction collector.

PMID- 8258639
TI  - Rapid, sensitive and efficient HPLC assays for HIV-1 proteinase.
AB  - The proteinase encoded by human immunodeficiency virus type 1 (HIV-1) cleaves
      peptide substrates of sequences derived from processing sites in HIV-1 gag-pol
      polypeptide. Based on this cleavage, assays that utilize HPLC to measure activity
      of HIV-1 proteinase are reported herein. In the assay first described, a baseline
      separation of unlabeled substrate and products is achieved with a run time of 10
      min and UV detection. Enzyme concentrations as low as 1 nM, which is the lowest
      reported for an assay employing underivatized peptide substrate, are attained.
      Even more powerful, versatile and sensitive, a second method that takes advantage
      of a peptide substrate labeled at its N-terminus with the fluorescein derivative
      is described as well. Because of the fluorescein label, this method offers
      several superior features, including very fast analysis of substrate and product
      in less than 3 min and fluorescence detection which provides essentially total
      freedom from interference. Synthesis of fluorescein-labeled peptide substrate is
      accomplished by solid-phase peptide synthesis.

PMID- 8258640
TI  - Isoelectric focusing in a multicompartment electrolyzer with zwitterionic
      membranes, exemplified by purification of glucoamylase.
AB  - A highly purified preparation of glucoamylase G1 from Aspergillus niger was
      found, by isoelectric focusing in immobilized pH gradients, to contain a major
      form with a pI of 3.50 and a number of minor, more acidic and more basic
      contaminants. The major isoform was purified to homogeneity by recycling
      isoelectric focusing in a multicompartment electrolyzer, by confining this form
      in between two zwitterionic membranes, with pI 3.49 at the anodic side and pI
      3.52 at the cathodic side. Recoveries were high (90%) and, notwithstanding the
      rather low operational pH, the electrosmotic flow was minimal and no protein
      precipitation occurred up to concentrations of 2.5 mg/ml (at the isoelectric
      point). The forms resolved in an analytical focusing gel were subjected to two
      types of in situ enzyme detections, by the glucose oxidase peroxidase (GOP) test
      and by the starch-iodine test. By both criteria all resolved zones exhibited
      enzyme activity, the GOP assay, however, following more closely the Coomassie
      blue stained protein profile. By computer modelling, it is shown that it is
      impossible to obtain linear pH gradients at such low pH values (pH 2.5-4.5
      intervals) when the mixture has a low buffering power (beta = 2.0 mequiv.l-1 pH
      1). When the beta power was gradually raised (beta = 4, beta = 6, beta = 8) the
      pH gradient became progressively linear until, in a recipe with beta = 10
      mequiv.l-1 pH-1 full linearity of the pH gradient could be obtained. This is
      shown to be due to the substantial buffering power of bulk water in the pH 2.5
      3.5 region.

PMID- 8258641
TI  - New reagents for spectral titration of active site of chymotrypsin.
AB  - The reaction of alpha-chymotrypsin (ChT) with 2-phenyl-(E)-[4-(E)
      cinnamylidene]oxazolin-5-one (E-PCO) or 2-phenyl-(Z)-[4-(E)
      cinnamylidene]oxazolin-5-one (Z-PCO) at pH 4.5 and 25 degrees C led to the
      quantitative accumulation of the corresponding acyl-ChT intermediate. Very large
      changes in molar extinction coefficient were observed in the visible region
      during the conversion of the oxazolinones to the acyl-ChT intermediates. This
      afforded a reliable method for the spectral titration of ChT in the visible
      region. Both E-PCO and Z-PCO were stable under these conditions and did not cause
      any complication in the titration of the active site.

PMID- 8258642
TI  - Effect of human prolactin administration on gonadotropin and thyrotropin
      secretion in normal men.
AB  - To test the hypothesis that PRL is able to feedback negatively on its own
      secretion (short-loop feedback) in humans via augmentation of the turnover of
      tuberoinfundibular dopamine (TIDA), the effects of the administration of purified
      hPRL on endogenous LH, FSH and TSH were assessed. Purified hPRL, given in an i.v.
      loading dose of 90 micrograms followed by a continuous infusion of 1.39
      micrograms/min to 4 normal male volunteers resulted in a tripling of PRL levels
      (10.5 +/- 1.9 micrograms/L increasing to 30.9 +/- 3.6 micrograms/L) at the end of
      90 min. There were no changes in LH, FSH or TSH levels, however, during or
      following the infusion. Purified hPRL was also given in 1 and 8 micrograms/kg
      doses IM to 5 normal male volunteers. Although PRL levels did not rise
      significantly with the 1 microgram/kg dose, levels almost doubled with the 8
      micrograms/kg dose (9.5 +/- 2.2 micrograms/L increasing to 17.4 +/- 1.5
      micrograms/L). Again, LH, FSH and TSH levels did not change significantly over
      the three hour period of sampling with either dose. In conclusion, in this study
      we found that a 2-3 fold increase of circulating PRL levels maintained for 1.5-3
      h exerted no apparent effects on the secretion of endogenous LH, FSH and TSH.
      This study provides direct evidence against the existence of a short-loop
      feedback occurring via TIDA activation in humans over this time interval but does
      not rule out the possibility that such feedback may occur with more prolonged
      states of hyperprolactinemia or via other mechanisms or the possibility of an
      effect on the hypothalamic pulse generator.

PMID- 8258644
TI  - The National Register of infants with congenital hypothyroidism detected by
      neonatal screening in Italy.
AB  - Neonatal screening for congenital hypothyroidism began in Italy in 1977 and then
      progressively developed covering 94% of live births in 1991. The National
      Register of infants with congenital hypothyroidism was established in 1987 as a
      project of the Health Ministry. The results of the Register provided valuable
      epidemiological information about congenital hypothyroidism in Italy and
      evidenced some aspects in the screening organization which had to be improved.
      Discussion of Register data during annual national meetings has recently allowed
      an improvement of the screening program with particular regard to the beginning
      of therapy with L-thyroxine and its dose.

PMID- 8258643
TI  - Hormonal and radiological effects of megavoltage radiotherapy in patients with
      growth hormone-secreting pituitary adenoma.
AB  - Nineteen acromegalic patients (12 females and 7 males, aged 24-71 yr) were
      studied for 1-6 yr after radiotherapy (RT), administered by X-rays (18 MeV) by
      linear accelerator, with parallel opposite beams (doses 45-50.4 Gy, 1.8 Gy
      daily). Basal GH levels gradually decreased from 6.3-76.2 micrograms/L (mean +/-
      SE, 27.8 +/- 4.9) to 0.3-43.4 micrograms/L (11.7 +/- 3.6 micrograms/L; p < 0.005)
      at the last assessment. The earliest significant decrease was observed after one
      yr (14.9 +/- 3.8 micrograms/L; p < 0.005). Significant changes were observed also
      in IGF-I values (basal values 1.93-6.85 mU/ml, 3.22 +/- 0.30; last assessment
      0.55-4.57 mU/mL, 1.58 +/- 0.31; p < 0.01). The earliest significant decrease of
      IGF-I values was observed after 2 yr (1.61 +/- 0.16 mU/ml; p < 0.005). GH levels
      < 5 micrograms/L together with normal IGF-I values were observed in 9 patients, 2
      4 yr after RT. No changes were observed in PRL values, either in patients with
      pretreatment normal or elevated PRL levels. The CT and/or MRI picture of
      macroadenoma disappeared after 6-12 months in 3/12 patients. Moreover, a
      reduction (20-55%) in the diameter of the adenoma was shown after 6-36 months in
      other 4 patients. After RT 5/16 (31%) patients required cortisol and 4/19 (21%)
      thyroid replacement therapy. In 2/3 men a gonadal impairment was shown, that did
      not occur in the three female patients with normal gonadal function before
      RT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258645
TI  - Ovariectomy increases the level of estrogen receptor mRNA and estrogen receptor
      binding sites in female rat adipose tissue.
AB  - The roles of estrogen in the changes in estrogen receptor (ER) mRNA and ER
      binding sites in rat adipose tissue were studied in female rats. To elucidate the
      mechanism(s) behind ovariectomy (OVX)-induced obesity, the levels of ER mRNA and
      ER binding sites in adipose tissue were analyzed three weeks after OVX using
      Northern blot analysis of ER mRNA and the [3H]E2 binding assay, respectively. OVX
      induced an increase in body weight, and replacement of estradiol (E2) prevented
      that increase. Significant increases in the amounts of ER mRNA and in [3H]E2
      specific binding were observed after OVX, and E2 replacement reduced both of
      those increases. These results suggest that E2 may regulate rat obesity directly
      through ER in adipose tissues.

PMID- 8258646
TI  - Variability in the growth hormone response to growth hormone-releasing hormone
      alone or combined with pyridostigmine in type 1 diabetic patients.
AB  - In man the GH response to GHRH is variable within and between subjects.
      Pyridostigmine (PD), an acetylcholinesterase inhibitor, has been shown to reduce
      the variability of the GH response to GHRH in normal subjects. The aim of this
      study was to assess the existence of either inter- or intraindividual variability
      in the GH response to GHRH in type 1 diabetic patients. Moreover, we investigated
      the effect of PD on such variability in the same patients. Seven (4 females-3
      males) nonobese type 1 diabetic patients underwent two experiments performed in
      consecutive days according to a single-blind protocol: 1) 120 mg oral PD 60 min
      before iv injection of human (h) GHRH-(1-29) NH2, 100 micrograms in 2 ml of
      sterile water; 2) oral placebo 60 min before iv injection of 100 micrograms
      hGHRH. The two experiments were then repeated, following the same procedure, one
      and two weeks after the start of the study. The GH peaks after GHRH were variable
      within different subjects but also in the same subject on different occasions.
      However, the mean GH peak levels after GHRH in the three tests were not
      significantly different (14.2 +/- 3.5, 15.3 +/- 3, 16.5 +/- 6.4 micrograms/L,
      respectively), the coefficient of variation for each test was 65%, 51.8%, 102.4%,
      respectively (mean 73.1 +/- 15.1%). The GH response to GHRH was always
      significantly enhanced by PD administration: the mean GH peak levels in the three
      tests were 31.9 +/- 7.1, 44.8 +/- 10.4, 49.9 +/- 13.1 micrograms/L, respectively,
      without significant differences between tests.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258647
TI  - Cellular stress and glucocorticoid hormones protect L929 mouse fibroblasts from
      tumor necrosis factor alpha cytotoxicity.
AB  - Adaptive responses to the environment depend on the induction of the "stress
      response" in less differentiated organisms and cultured cells and the activation
      of the hypothalamic-pituitary-adrenal axis in animals and humans. This indicates
      that adrenal steroids and stress proteins play an important role in regulating
      cell survival in response to noxious stimuli. In an in vitro model, we analyzed
      the effects of either dexamethasone (DEX) treatment or environmental changes
      which can elicit a stress response, on the survival of cultured L-929 mouse
      fibroblasts exposed to the cytotoxic cytokine tumor necrosis factor alpha (TNF
      alpha). DEX treatment produced a significant reduction in the apoptotic death of
      L-929 cells produced by TNF-alpha. Abrogation of the protective effect of DEX by
      actinomycin D and cycloheximide demonstrated that protection against TNF-alpha
      requires de novo synthesis of mRNA and proteins. The results were similar when L
      929 cells were exposed to metabolic (serum starvation) or thermal (heat shock)
      stresses before TNF-alpha treatment. In both cases the stress process afforded
      significant protection against TNF-alpha cytotoxicity. Inhibition of mRNA and
      protein synthesis abrogated the protection exerted by stress (serum starvation)
      or produced massive death during the stress event (heat shock). The similarities
      in the protective activities of DEX and stress response and the reported
      interactions between heat shock proteins and glucocorticoid hormones suggest that
      stress proteins and glucocorticoids both belong to an ancient evolutionary
      pathway which controls cell survival.

PMID- 8258648
TI  - Effect of pulse frequency and amplitude of D-Trp6-luteinizing hormone-releasing
      hormone on the pulsatile secretion of prolactin and LH.
AB  - This work analyzes the effect of the pulse amplitude and frequency of a potent
      LHRH analog, D-Trp6-LHRH, in a perfusion system of isolated rat pituitary cells.
      To this purpose, we studied the LH and PRL secretion in different conditions:
      basal secretion, secretion after increasing concentrations of D-Trp6-LHRL (0.001,
      0.01, 0.1 and 1 nM) secretion in function of the pulses frequency (2,3, and 4
      pulses per h) and amplitude (0.1, 1 and 10 nM). The principal findings were: 1.
      The basal LH and PRL secretions was pulsatile; 2. The stimulation of LH by the
      analog was not dose-dependent; 3. When more than 2 pulses per h were
      administered, a rapid desensitization of gonadotroph to release LH (at 20-30 min)
      occurred; 4. There was a loss of pulsatility of PRL secretion with an increase in
      the pulse frequency and amplitude of the D-Trp6-LHRH, which was produced
      parallelly to the desensitization of the gonadotroph to release LH. In summary,
      these findings suggest that a rapid loss of pulsatility of the PRL when the D
      Trp6-LHRH pulse frequency and amplitude is increased might be due to the early
      desensitization of the gonadotroph to the analog.

PMID- 8258649
TI  - Reduced activation of suppressor T lymphocytes by specific antigens in autoimmune
      thyroid disease.
AB  - In order to study the activation of suppressor T lymphocytes by thyroid-specific
      antigens in autoimmune thyroid disease (AITD), we have investigated the effects
      of the organ-specific antigens, thyroperoxidase (TPO), thyroglobulin (Tg), and
      thyroid microsomal antigen (TMc), as well as renal microsomes (RMc) as a control
      antigen, on the activation of suppressor T lymphocytes; this was accomplished by
      measuring major histocompatibility complex class II (HLA-DR) expression on their
      surfaces by flow cytometric analysis. Peripheral blood mononuclear cells (PBMC),
      obtained from 33 patients with Graves' disease (GD), 26 with Hashimoto's
      thyroiditis (HT), 5 with nontoxic nodular goiter (NTG), and 30 normal persons
      (N), were cultured for 7 days in the presence or absence of TPO, Tg, or RMc at
      final concentration of 10, 100, and 1000 ng/ml. Cultured cells were stained with
      fluorescent-conjugated monoclonal antibodies (anti-CD8, anti-CD11b, and anti-HLA
      DR), and the activation of CD8+ and CD8+CD11b+ (pure suppressor) T cells by the
      antigens was analyzed on a flow cytometer. In the absence of antigen, i.e., the
      autologous mixed lymphocyte reaction (AMLR), CD8+ and CD8+CD11b+ T lymphocytes
      from patients with GD and HT showed significantly lower activation as compared to
      N. We measured the Stimulation Index (Sl) of activated T lymphocytes to compare
      antigen-specific activation between CD8+ and CD8+CD11b+ cells from normal persons
      and patients. With stimulation of 100 and/or 1000 ng/mL of TPO or Tg, Sl of
      activated CD8+ cells was significantly (p < 0.05 to 0.01) lower in GD and HT as
      compared with N.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258650
TI  - Hormonal pattern in women affected by rheumatoid arthritis.
AB  - Gonadal sex hormones may account for the sexual dimorphism in the immune response
      and for the greater incidence of autoimmune disease in females. We have
      previously reported the presence of progesterone (P) deficiency in female
      patients with thyroid and ovarian autoimmune disease. In this context, the
      hormonal profile in 9 women with rheumatoid arthritis (RA) and in 9 age-matched
      ealthy women, were evaluated to verify the presence of a steroid hormone
      secretion impairment in a systemic autoimmune disease, further supporting our
      hypothesis of P deficiency involvement. P and androgen plasma levels, in the
      luteal phase, were significantly lower (p < 0.05 and 0.005, respectively) in RA
      patients than in the control group, with a consequent decrease of the free
      androgen index. Moreover, despite normal cortisol values, corticosterone (B)
      plasma levels were significantly higher in the RA patients (p < 0.01 and 0.05 in
      follicular and luteal phase, respectively). Therefore, our present data confirm
      the androgen deficiency in patients with a systemic autoimmune disease, such as
      RA and support the immunomodulator effect of P. Finally, the higher B plasma
      levels in RA patients may suggest the presence of a slight impairment of the
      immune hypothalamic-pituitary-adrenal axis (HPAA), supporting its role in certain
      phases of RA pathogenesis. In conclusion, in addition to androgens, the
      immunomodulator role of P should also be taken into account in the pathogenesis
      of the systemic autoimmune disease.

PMID- 8258652
TI  - Magnetic resonance characterization of a long-standing pituitary abscess.
AB  - A 56-year-old male patient with panhypopituitarism is presented. Magnetic
      resonance (MR) examination of the pituitary region revealed a pituitary mass with
      markedly increased signal intensity on T1-weighted images and low signal
      intensity on T2-weighted images. At surgery, a large amount of purulent material
      was removed. At light microscopy, the tissue was demonstrated to be a pituitary
      abscess occurring in an otherwise normal pituitary gland. The high signal
      intensity on T1-weighted images does not correspond to the only MR description of
      a pituitary abscess given until now, reporting a mass isointense to white matter.
      These signal characteristics could emanate from the presence of small amounts of
      blood breakdown products in the proteinaceous content of the abscess. MR
      appearance of a pituitary abscess is possibly aspecific and could depend on the
      pathological composition of the lesion.

PMID- 8258651
TI  - Immunolike growth hormone substance in tissues from human embryos/fetuses and
      adults.
AB  - GH immunolike reactivity was measured by RIA and IRMA tests in the extracts of
      tissues from human fetuses (8-32 weeks) and adults. For some fetal tissues a
      comparison was made with the T4 values obtained in a previous study. Both
      hormones were already measurable in peripheral tissues at 8 weeks of gestation.
      The increase in GH was faster than for T4 and it reached the zenith at
      approximately 20 weeks; thereafter, the GH concentration declined until delivery.
      In contrast, T4 progressively increased until term. Thirteen tissues were studied
      both in fetuses and in adults: the GH concentration was about 10 times higher in
      fetal tissues, with the exception of the brain and the pancreas. The brain showed
      the lowest GH concentration throughout fetal life and adulthood, whereas the
      highest GH levels were recorded in adults' pancreas, but they resulted to be
      artifacts since the RIA values were not confirmed by the IRMA test. In both
      groups of subjects the highest GH concentrations were found in kidneys, liver and
      small intestine; the lowest, beyond the brain, in red muscle and cartilage. Thus,
      the pattern of the quantitative distribution of GH in fetal tissues is the same
      as in adults, suggesting a functional role of the hormone in the developing human
      during the prenatal period, in contrast with the concept that high tissue levels
      of GH are a mere reflection of high GH blood levels. Moreover, in all tissues
      examined no correlation was found between GH and T4 concentration.

PMID- 8258653
TI  - Multiple pituitary hormone deficiencies in a patient with spinocerebellar ataxia:
      magnetic resonance imaging and hormonal studies.
AB  - Degenerative spinocerebellar ataxia has a rare association with hypogonadotropic
      hypogonadism. In this report we present the results of the detailed endocrine
      evaluation and magnetic resonance imaging in one such patient. A 20-year-old male
      with progressive cerebellar ataxia, hypogonadism, and short stature was
      investigated. Basal testing revealed hypogonadotropic hypogonadism (LH < 5 mU/L,
      FSH < 5 mU/L, testosterone 2.5 nM/L). There was no rise in LH after stimulation
      with LHRH, peak LH level being < 5 mU/L. Insulin hypoglycemia testing was
      consistent with GH deficiency, with peak GH being 3.2 mU/L. On TRH stimulation,
      there was no significant rise in prolactin, though the TSH response was normal.
      Magnetic resonance imaging revealed cerebellar atrophy. The anterior pituitary
      was atrophic, with a height of 1.4 mm. The posterior pituitary and the pituitary
      stalk were normal in size and position. This patient with degenerative
      spinocerebellar ataxia had multiple pituitary hormone deficiencies. The results
      of our endocrine evaluation and MR imaging lead us to believe that these deficits
      may result from a lesion at the level of the pituitary gland.

PMID- 8258654
TI  - Insulin-dependent diabetes mellitus associated with Graves' disease and
      idiopathic hypoparathyroidism.
AB  - We report a case of 26-year-old woman with Graves' disease and idiopathic
      hypoparathyroidism diagnosed at 11 years of age, who subsequently developed
      insulin-dependent diabetes mellitus (IDDM) at 17 years of age. Treatment with
      antithyroid agents had failed to control her Graves' disease and her IDDM was
      unmanageable despite insulin therapy. Surgical intervention was carried out,
      resulting in an improvement of both her hyperthyroidism and IDDM. This case is
      the first report of polyglandular autoimmune (PGA) syndrome, presenting the
      association of IDDM, Graves' disease and idiopathic hypoparathyroidism.

PMID- 8258655
TI  - Hormone measurement in blood from inferior petrosal sinus: clinical and
      experimental implications.

PMID- 8258656
TI  - The positive side of health care spending.

PMID- 8258657
TI  - New guidelines for treating major depression.

PMID- 8258658
TI  - Medicaid official hopes plan improves access. Interview by Bob Carlson.

PMID- 8258660
TI  - Physicians fine-tune offices with PA/QI program.

PMID- 8258659
TI  - Consultants urge doctors to prepare for future.

PMID- 8258662
TI  - Bibliography of the current world literature in hypertension.

PMID- 8258661
TI  - Double cardiac valve replacement: a community hospital experience.
AB  - The morbidity and mortality of double cardiac valve replacement were assessed in
      a community hospital setting. Four hundred twenty-two cardiac patients undergoing
      valve replacement from 1977 to 1991 were analyzed. Forty-two patients underwent
      double valve replacement. The clinical variables associated with increased
      operative mortality (early and late) were determined. The overall operative
      mortality rate for valve replacement was 7.87% (29 of 422 patients). The
      mortality rate was 9.09% (3/33 patients) for double valve replacement and 11.11%
      (1/9 patients) for double valve replacement in conjunction with coronary bypass.
      The clinical variables associated with increased mortality were: significant
      reduction in preoperative left ventricular ejection fraction (< 35%); advanced
      age (> 60); presence of ischemic mitral valve disease; and preoperative
      functional class (New York Heart Association Functional Class IV). The results of
      this study suggest that strategies to diminish operative mortality should include
      assessment of risk preoperatively as well as anticipation of high mortality in
      selected subgroups.

PMID- 8258663
TI  - Sudden cardiac death, ventricular arrhythmias and hypertensive left ventricular
      hypertrophy.
AB  - OBJECTIVE: To evaluate the relationship between sudden cardiac death, ventricular
      arrhythmias and left ventricular hypertrophy in patients with hypertension. DATA
      IDENTIFICATION: Epidemiological studies assessing the importance of left
      ventricular hypertrophy as a risk factor for sudden cardiac death, studies
      assessing the prevalence of arrhythmias in left ventricular hypertrophy and
      studies assessing whether there is an electrophysiological substrate in the
      hypertrophied myocardium for ventricular dysrhythmias. RESULTS OF DATA ANALYSIS:
      Current evidence indicates that left ventricular hypertrophy is a risk factor for
      sudden cardiac death and that ventricular arrhythmias are more prevalent in
      hypertensive patients with than in those without left ventricular hypertrophy.
      However, there is a lack of evidence that these dysrhythmias are important as an
      underlying mechanism for sudden cardiac death, and there is no clear evidence
      that the hypertrophied myocardium is, itself, an arrhythmogenic substrate for
      malignant ventricular dysrhythmias. One possible mechanism for sudden cardiac
      death is myocardial ischaemia, either as a consequence of associated coronary
      disease or due to left ventricular hypertrophy, but this remains unproved.
      CONCLUSIONS: There is currently no evidence that the ventricular ectopic activity
      seen in patients with hypertensive left ventricular hypertrophy is a marker for
      sudden cardiac death. Clarification of the mechanisms involved in sudden cardiac
      death will help in selecting appropriate preventive and therapeutic strategies
      for these patients.

PMID- 8258664
TI  - Which factor mediates reno-renal control of renin gene expression?
AB  - OBJECTIVE: To obtain information about possible pathways mediating the
      suppression of renin gene expression in the contralateral kidneys of stenosed
      kidneys. DESIGN: The effects of unilateral renal denervation and of treatment
      with an angiotensin II antagonist (losartan) on renal renin gene expression were
      examined in a two-kidney, one-clip model. METHODS: Renal renin messenger RNA
      levels, plasma renin activity, blood pressure and kidney weights were monitored
      over 10 days in adult male Sprague-Dawley rats with various unilateral reductions
      of renal blood flow achieved with silver clips of 0.2, 0.3 and 0.4 mm inner
      diameter. RESULTS: With all the clip sizes used, renin messenger RNA levels
      increased transiently in the clipped kidneys, the time course and the magnitude
      of the increase being dependent on the degree of flow reduction. In the
      contralateral kidneys clipping caused sustained decreases in renin messenger RNA
      to levels proportional to the clip size. The suppression of renin gene expression
      in the contralateral kidneys was not related to compensatory growth of the organs
      nor to changes in plasma renin activity or arterial pressure. Unilateral
      denervation of the kidney before clipping had no influence on the characteristic
      increase and decrease in renin messenger RNA in the stenosed and contralateral
      kidneys, respectively. Treatment of the rats with losartan led to fourfold
      increases in renal renin messenger RNA levels and to sixfold increases in plasma
      renin activity in control rats. A 0.3-mm clip did not further increase renin
      messenger RNA or plasma renin activity in losartan-treated rats but again led to
      suppression of renin messenger RNA in the contralateral kidney to 50% of the
      levels found in the clipped kidneys. CONCLUSIONS: The results suggest that the
      suppression of renin gene expression in the contralateral kidneys of stenosed
      kidneys is not due to compensatory renal growth nor mediated by systemic blood
      pressure, angiotensin II AT1 receptors or renal nerves. We therefore hypothesize
      that kidneys with reduced perfusion release a humoral factor that acts as a
      potent inhibitor of renin gene expression.

PMID- 8258665
TI  - The vasorelaxant effect of deuterium oxide is secondary to calcium-induced
      liberation of nitric oxide by endothelial cells.
AB  - OBJECTIVE: To test the hypothesis that deuterium oxide (D2O) might induce
      endothelium-dependent and nitric oxide-mediated vasodilation by altering
      intracellular calcium concentration ([Ca2+]i) in vascular endothelial cells.
      DESIGN: The endothelium-dependent and nitric oxide-mediated regulation of
      vascular tone by D2O was first examined in perfused rat mesenteric arterial beds.
      Direct effects of D2O on [Ca2+]i in cultured vascular endothelial cells were then
      examined in order to elucidate a cellular mechanism for D2O-induced vasodilation.
      METHODS: Vascular reactivity was assayed by measuring the perfusion pressure of
      isolated rat mesenteric arterial beds. [Ca2+]i in cultured bovine and rat
      vascular endothelial cells was measured with the fura-2 fluorescence technique.
      RESULTS: D2O relaxed precontracted rat mesenteric arterial beds with an intact
      endothelium. This effect of D2O was either inhibited by N omega-nitro-L- arginine
      (a nitric oxide synthase inhibitor) or eliminated by the removal of endothelium.
      In cultured bovine aortic, rat aortic, and rat tail artery endothelial cells, D2O
      induced a biphasic increase in [Ca2+]i, with a characteristic initial transient
      increase followed by various patterns of sustained [Ca2+]i increase. The
      sustained phase was entirely dependent on the extracellular calcium entry.
      CONCLUSIONS: A direct effect of D2O on [Ca2+]i in vascular endothelial cells may
      be responsible for the endothelium-dependent, presumably nitric oxide-mediated,
      vasodilation induced by D2O in precontracted vessels. From these results new
      mechanisms can be explored for the antihypertensive effect of D2O and new avenues
      can be developed to study the functional integrity of the endothelium-dependent
      regulation of the vascular tone.

PMID- 8258666
TI  - Role of vasopressin, the renin-angiotensin system and sex in Dahl salt-sensitive
      hypertension.
AB  - OBJECTIVE: To determine the roles of vasopressin, the renin-angiotensin system
      and sex in the pathogenesis of salt-sensitive hypertension in the Dahl rat.
      DESIGN: The effects of 12 days' treatment with a non-peptide, orally effective V1
      antagonist (OPC-21,268) and captopril, individually or together, were compared in
      male and female Dahl salt-sensitive rats after 10 days on a high-salt diet.
      METHODS: OPC-21,268 was given in the food, and captopril was administered with
      osmotic pumps implanted subcutaneously. RESULTS: Systolic blood pressure (SBP)
      reached a higher level in untreated males than in untreated females. V1 blockade
      in males prevented any further increase in SBP during the first week of
      treatment, but SBP rose thereafter towards the levels found in the untreated
      males. In females OPC-21,268 had no effect. In males captopril prevented any
      further increase in SBP. There was no effect of captopril in females during the
      first week of treatment, but SBP fell to pretreatment levels during the second
      week. Combined treatment with OPC-21,268 and captopril in males had a smaller
      antihypertensive effect than either drug alone. In females combined treatment
      prevented any further increase in SBP. CONCLUSIONS: These findings suggest that
      both vasopressin and the renin-angiotensin system contribute to the pathogenesis
      of Dahl salt-sensitive hypertension, but that other factors, possibly including
      the sympathetic nervous system, are also involved. Sex also affects the severity
      of this form of hypertension and influences the relative roles of vasopressin and
      the renin-angiotensin system. It is likely that the gonadal steroid hormones
      modulate the activity of the pathogenetic factors in this form of hypertension at
      a central or peripheral level.

PMID- 8258667
TI  - Cerebrospinal fluid kallikrein in spontaneously hypertensive and
      desoxycorticosterone acetate-salt hypertensive rats.
AB  - OBJECTIVE: To determine whether immunoreactive tissue kallikrein levels in
      cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and
      desoxycorticosterone acetate (DOCA)--salt-treated hypertensive rats are elevated
      compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats. DESIGN:
      The present study was designed to test the hypothesis that the activity of the
      brain tissue kallikrein-kinin system is enhanced in hypertensive states. METHODS:
      Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague-Dawley rats treated
      for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in
      the drinking water, or with vehicle and tap water to drink, were studied. CSF was
      collected from a cannula inserted into the cisterna magna, and was frozen until
      the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial
      pressure in the SHR and WKY rats was measured directly via a cannula inserted in
      the femoral artery or by tail-cuff plethysmography. RESULTS: In adult 18- to 19
      week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The
      CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of
      kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF
      kininogenase activity in SHR was significantly higher than that in age-matched
      WKY rats. In DOCA--salt hypertensive rats the CSF kallikrein concentration was
      higher than in vehicle-treated control rats. Acute elevation of blood pressure
      with a 120-min intravenous phenylephrine infusion did not change the CSF
      kallikrein concentration in 50 rats compared with vehicle-treated control rats.
      This is the first study to quantitate immunoreactive tissue kallikrein in the CSF
      of rats and to show elevated levels of CSF kallikrein in hypertensive rats
      compared with normotensive rats. CONCLUSION: The present data suggest that higher
      brain kallikrein activity in hypertensive rats may play a role in the development
      of elevated blood pressure.

PMID- 8258668
TI  - Vascular conversion of angiotensin I in stroke-prone spontaneously hypertensive
      and Wistar-Kyoto rats.
AB  - OBJECTIVE: Linkage studies have shown that the gene locus for angiotensin
      converting enzyme (ACE) is associated with the expression of hypertension in
      stroke-prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis
      that the conversion of angiotensin I (Ang I) to angiotensin II (Ang II) in blood
      vessels is elevated in SHRSP. DESIGN: We measured the conversion rate of Ang I to
      Ang II during one pass through an isolated resistance vessel bed. We used the
      same substrains of SHRSP and Wistar-Kyoto control rats (WKY) that had been
      employed in the earlier linkage studies. METHODS: Isolated hindquarters from
      young and adult (10- to 12- and 36- to 38-week-old) rats were perfused with an
      artificial medium and then infused with Ang I at 0.5 and 2 pmol/ml. Ang I and II
      were measured with high-performance liquid chromatography and radioimmunoassay in
      hindquarter effluent and in blank control channels. Conversion and extraction
      rates were calculated from angiotensin levels in hindquarter and blank perfusion
      channels, respectively. RESULTS: The conversion rates of Ang I to Ang II did not
      differ between SHRSP and WKY in young or in adult rats. Captopril completely
      abolished the formation of Ang II in all groups of rats. During infusion at the
      higher dose of Ang I, the extraction of Ang I was significantly decreased in
      SHRSP compared with WKY. CONCLUSIONS: Our results are consistent with the notion
      that the metabolism of angiotensin is decreased in spontaneously hypertensive
      rats. However, we found no support for the hypothesis that vascular ACE is
      responsible for high blood pressure in SHRSP. These findings suggest that other
      genes close to the ACE locus or the hyperexpression of the enzyme in other areas
      may contribute to hypertension in these rats.

PMID- 8258669
TI  - Production of nerve growth factor by cultured vascular smooth muscle cells from
      spontaneously hypertensive and Wistar-Kyoto rats.
AB  - OBJECTIVE: Nerve growth factor (NGF) is a neurotrophic protein which acts on
      peripheral sympathetic nerves. Elevated NGF in vascular tissues of young
      spontaneously hypertensive rats (SHR) has been reported. The aim of the present
      study was to compare the amount of NGF secreted from cultured vascular smooth
      muscle cells (VSMC) and mesenteric artery and thoracic aorta segments from SHR
      and Wistar-Kyoto (WKY) rats. METHODS: VSMC prepared by the enzyme digestion
      method from the thoracic aortic media of 14-week-old SHR and age-matched WKY rats
      were subcultured in Dulbecco's modified Eagle's medium containing 10% fetal calf
      serum. Segments of mesenteric artery and thoracic aorta from 4-week-old SHR and
      age-matched WKY rats were similarly cultured. The NGF content in conditioned
      medium was measured using an enzyme immunoassay. The protein content of VSMC was
      measured by the Lowry method. RESULTS: Total NGF content in the cell culture
      medium was increased during an exponential growth phase and then gradually
      decreased during a quiescent phase in both rat strains. There were no significant
      differences in the levels of NGF secreted from mesenteric artery and thoracic
      aorta segments between the SHR and WKY rats. The differences in cellular protein
      content between SHR and WKY rats were very small. CONCLUSIONS: In contrast to the
      reports of increased NGF in SHR tissues, our data demonstrate that NGF secretion
      was lower in VSMC from SHR, and was equivalent in mesenteric artery and thoracic
      aorta segments from SHR and WKY rats. We have no clear explanation for these
      observations, but the present results indicate that upregulation of NGF in SHR
      tissues is not responsible for a simple enhancement of NGF synthesis in VSMC, and
      suggest a breakdown of the regulatory mechanism or mechanisms of NGF gene
      expression in SHR tissues.

PMID- 8258670
TI  - Decreased ATP sensitivity of a K+ channel and enhanced vascular smooth muscle
      relaxation in genetically hypertensive rats.
AB  - OBJECTIVE: To characterize an ATP-sensitive K+ channel at the single-channel and
      tissue level in the vascular smooth muscle of normotensive and genetically
      hypertensive rats. METHODS: Age- and sex-matched Wistar-Kyoto (WKY) rats and
      stroke-prone spontaneously hypertensive rats (SHRSP) were used. Patch-clamp
      single-channel recording was used to measure K+ channel activity in dissociated
      tail artery cells. The effect of the K+ channel-opener diazoxide and the specific
      ATP-sensitive K+ channel antagonist glyburide on isometric force development in
      isolated tail artery strips was determined by a standard muscle bath technique.
      RESULTS: The concentration of ATP that caused half-maximal reduction in channel
      activity was greater in the SHRSP than in the WKY rats. Tail artery strips and
      cells from SHRSP were more sensitive to the effect of diazoxide on relaxation and
      channel activity, and less responsive to the effect of glyburide, than were those
      from WKY rats. CONCLUSIONS: The decreased ATP sensitivity of this K+ channel may
      partly compensate for the increased vascular reactivity in hypertension, and the
      change in this property of the channel may be responsible for the altered
      sensitivity to diazoxide and glyburide in SHRSP.

PMID- 8258671
TI  - Inhibition of protein synthesis and antiproliferative effect of the angiotensin
      converting enzyme inhibitor trandolaprilat in rat vascular smooth muscle cells.
AB  - OBJECTIVE: To investigate the effect of the angiotensin converting enzyme (ACE)
      inhibitor trandolaprilat on vascular smooth muscle cell growth, and to analyse
      its mechanism of action. DESIGN: Aortic vascular smooth muscle cells (VSMC) from
      Wistar-Kyoto rats were cultured, and cell proliferation was analysed using a cell
      synchrony technique. METHODS: Proliferative activity was assessed by [3H]
      thymidine uptake and doubling time. Protein synthesis was assessed by [3H]
      leucine incorporation. Actin formation was measured using sodium dodecylsulphate
      polyacrylamide slab gel electrophoresis and a densitometric assay. The effect of
      trandolaprilat on translational protein synthesis was also examined using the
      cell-free protein synthesis system of reticulocyte lysate and messenger RNA from
      VSMC. RESULTS: Trandolaprilat decreased [3H]-thymidine uptake and increased the
      doubling time of randomly cycling VSMC. The cell synchrony study revealed that
      this antiproliferative effect was due to increased transition time from S to G2
      M. Decreased cell cycle progression during G2-M was reflected by inhibition of
      cellular protein synthesis during this period. Cellular protein in randomly
      cycling VSMC was also decreased by trandolaprilat. This decreased protein
      synthesis was probably produced by inhibition of RNA translation. CONCLUSIONS:
      The ACE inhibitor trandolaprilat reduces VSMC proliferation by lengthening the G2
      M phase of the cell cycle, and produces a decrease in cellular protein content.
      This effect is probably mediated by inhibition of protein synthesis at the
      translational level.

PMID- 8258672
TI  - Persistent hypertension following inhibition of nitric oxide formation in the
      young Wistar rat: role of renin and vascular hypertrophy.
AB  - OBJECTIVE: To determine whether induction of arterial hypertension in young
      normotensive Wistar rats by chronic inhibition of nitric oxide production with NG
      nitro-L-arginine methyl ester (L-NAME) produced a form of self-sustained
      hypertension, and to investigate the role of the renin-angiotensin system and
      vascular hypertrophy in the hypertensive process. METHODS: Three-week-old Wistar
      rats were given 100 or 40 mg/kg per day L-NAME or 40 mg/kg per day L-NAME plus
      100 mg/kg per day captopril in their drinking water for between 4 and 7 weeks.
      Systolic blood pressure was measured by tail-cuff plethysmography both during
      treatment and after the treatment had been stopped. The effect of treatment on
      plasma renin was measured and the effect of treatment on mesenteric resistance
      artery structure was determined using a small-vessel myograph. RESULTS: L-NAME
      produced a progressive and marked increase in blood pressure during the period of
      treatment. Hypertension was sustained for 14 weeks after stopping treatment. L
      NAME resulted in a fourfold increase in plasma renin which remained elevated
      after treatment was stopped. Blood pressure was correlated with plasma renin
      levels. Treatment with L-NAME plus captopril markedly attenuated the rise in
      blood pressure and captopril also produced a marked fall in blood pressure in
      rats that developed persistent hypertension. Rats with self-sustained
      hypertension exhibited both cardiac and mesenteric resistance vessel hypertrophy.
      The induction of vascular hypertrophy with low-dose L-NAME did not result in the
      development of self-sustained hypertension. CONCLUSIONS: Chronic L-NAME treatment
      in young rats can produce a form of persistent hypertension which is renin
      dependent and which does not seem to involve a vascular amplifier mechanism.

PMID- 8258673
TI  - Na(+)-Ca2+ exchange modulates Ca2+ handling of human platelets by altering
      intracellular Ca2+ store size.
AB  - OBJECTIVE: In order to elucidate the role of Na(+)-Ca2+ exchange in regulating
      cytosolic free Ca2+ concentration in human platelets, we investigated the
      relationship between cytosolic free Na+ and Ca2+ concentrations in human
      platelets. METHODS: Sodium-binding benzofuran isophthalate and fura-2 were used
      to monitor cytosolic free Na+ and Ca2+ concentrations, respectively. RESULTS:
      Ouabain at a concentration of 100 mumol/l induced an increase in cytosolic free
      Na+ concentration within 5 min, followed by increases in resting cytosolic free
      Ca2+ concentration and intracellular Ca2+ store. These three parameters were
      increased in a time-dependent manner significantly above the timed control over a
      period of 60 min. Pre-incubation of platelets with 100 mumol/l ouabain for 30 min
      significantly enhanced the cytosolic free Ca2+ response to thrombin and arginine
      vasopressin in the absence of extracellular Ca2+. The decrease from peak
      cytosolic free Ca2+ concentration in response to ionomycin in the absence of
      extracellular Ca2+ was significantly slower in low-Na+ buffer than in standard
      buffer. In addition, 5 mumol/ionomycin increased the cytosolic free Na+
      concentration markedly in the presence of 0.1 mmol/l extracellular Ca2+, but the
      rise in cytosolic free Na+ concentration was suppressed by 2 mmol/l Ni2+ (NiCl2)
      or by removal of extracellular Ca2+. CONCLUSIONS: These results suggest that
      Na(+)-Ca2+ exchange is important in extruding Ca2+ from the cytosol in human
      platelets, and inhibition of this exchange leads to the accumulation of
      intracellular Ca2+ store, which may be responsible for the enhanced
      responsiveness of cytosolic free Ca2+ to agonists.

PMID- 8258674
TI  - Insulin-like growth factor 1 and sodium-lithium countertransport in essential
      hypertension and in hypertensive left ventricular hypertrophy.
AB  - OBJECTIVE: The aim of this work was to study the insulin-like growth factor 1
      (IGF1), a substance able to promote cell proliferation in vascular smooth muscle,
      in patients with mild-to-moderate hypertension and to analyse its relationship to
      sodium-lithium countertransport, a genetic marker of hypertension that is related
      to cardiovascular complications. METHOD: We studied 32 hypertensive subjects,
      some with left ventricular hypertrophy, and 14 healthy subjects. Fasting plasma
      IGF1 was measured by means of a radioimmunoassay after octadecylsilica
      chromatography and Na(+)-Li+ countertransport was determined by the method of
      Canessa. RESULTS: Hypertensive patients had higher values of both IGF1 and Na(+)
      Li+ countertransport. We found a positive correlation, irrespective of age,
      between IGF1 and Na(+)-Li+ countertransport. The patients with left ventricular
      hypertrophy had significantly higher plasma IGF1 levels than those without left
      ventricular hypertrophy. CONCLUSION: Our results confirm a possible role for IGF1
      in the cardiovascular complications of hypertension and emphasize its
      relationship to genetically determined factors.

PMID- 8258675
TI  - Low-density lipoprotein oxidation in essential hypertension.
AB  - OBJECTIVES: To investigate the occurrence of enhanced low-density lipoprotein
      (LDL) oxidation as an additional factor promoting atherosclerosis progression in
      hypertensive patients. DESIGN: The oxidation of plasma LDL was investigated in a
      group of untreated patients with mild-to-moderate essential hypertension without
      clinically evident target organ damage and in a group of control subjects.
      METHODS: LDL oxidation was evaluated as both the susceptibility to oxidation in
      vitro and the presence of plasma anti-oxidized LDL antibodies (as an index for
      oxidation in vivo). RESULTS: LDL from hypertensive subjects exhibited enhanced
      susceptibility to oxidation in vitro as revealed by early and accelerated
      generation of conjugated dienes after exposure to CuSO4. Vitamin E concentration
      in LDL from hypertensive subjects was slightly but significantly decreased and
      its efficiency in protecting LDL from oxidation was impaired. Furthermore, a
      higher plasma anti-oxidized LDL titre was found in hypertensive patients.
      Subclass analysis revealed that the contemporary presence of
      hypercholesterolaemia did not significantly modify either the increased
      susceptibility of LDL to oxidation or the presence of plasma anti-oxidized LDL
      antibodies detected in hypertensive patients. Moreover, no correlation was found
      between LDL oxidation parameters and blood pressure values. CONCLUSIONS: LDL from
      hypertensive patients is more susceptible to oxidation in vitro and is more
      promptly oxidized in vivo. These findings suggest a possible participation of LDL
      oxidation in promoting and accelerating the atherosclerosis that often develops
      in hypertensive patients.

PMID- 8258676
TI  - Improved baroreflex sensitivity in elderly hypertensives on lisinopril is not
      explained by blood pressure reduction alone.
AB  - OBJECTIVE: The major goals of this study were to determine whether lisinopril and
      nifedipine lowered blood pressure and improved carotid baroreflexes in older
      hypertensives. DESIGN: The effects of lisinopril at 10-40 mg/day versus
      nifedipine gastrointestinal therapeutic system (GITS) at 30-90 mg/day on blood
      pressure and baroreflex sensitivity were studied after 3 weeks each on (1) single
      blind placebo, (2) double-blind assignment to either lisinopril or nifedipine,
      (3) single-blind placebo, and (4) crossover to double-blind lisinopril or
      nifedipine. Measurements at the end of the four phases included 24-h blood
      pressure using the Accutracker, laboratory hemodynamics with the Dinamap and
      impedance cardiography, baroreflex sensitivity with the pneumatic neck chamber,
      and plasma samples for neurohumoral and metabolic activity. PATIENTS: Thirteen
      patients aged 55 years or older (mean +/- SEM 65 +/- 1 years) with mild-to
      moderate hypertension completed the study. MAIN OUTCOME MEASURES: The primary
      data for analysis across the four study phases included ambulatory blood pressure
      values, laboratory hemodynamics, and baroreflex sensitivity. RESULTS: Compared
      with the preceding placebo, lisinopril and nifedipine lowered 24-h blood pressure
      significantly. In the laboratory, the effects of both compounds on blood
      pressure, cardiac output, calculated total systemic resistance, and the stroke
      volume-pulse pressure relationship, an index of arterial compliance, were
      similar. Lisinopril was associated with a relative increase in the standing
      systolic blood pressure compared with nifedipine (P < 0.05). This coincided with
      an enhanced heart-rate (R-R interval) response to neck pressure, which also
      decreased carotid transmural pressure, with lisinopril versus nifedipine (P <
      0.05). CONCLUSIONS: Lisinopril and nifedipine were both effective as monotherapy
      for controlling blood pressure in these elderly patients. Despite similar effects
      on blood pressure and systemic hemodynamics, baroreflex sensitivity in response
      to a reduction in carotid transmural pressure was greater with lisinopril than
      with nifedipine.

PMID- 8258677
TI  - Disparate effects of exercise training on glucose tolerance and insulin levels
      and on ambulatory blood pressure in hypertensive patients.
AB  - OBJECTIVE: To assess the relationship of insulin levels and glucose tolerance to
      blood pressure in hypertension. DESIGN: An open, prospective trial of exercise
      training with ambulatory blood pressure monitoring and intravenous glucose
      tolerance testing before and after a 14-week training programme. PATIENTS: Twenty
      sedentary, untreated, non-obese, normoglycaemic individuals of both sexes with
      uncomplicated essential hypertension, of whom 16 completed the study.
      INTERVENTION: Fourteen weeks of supervised, low-intensity, group exercise of
      three 1-h sessions per week. MAIN OUTCOME MEASURES: Ambulatory and clinic blood
      pressure, and glucose and insulin responses to an intravenous glucose tolerance
      test. RESULTS: Maximal work capacity on a bicycle ergometer increased by 20% (P <
      0.001); 24-h ambulatory blood pressure was 143 +/- 12/87 +/- 5 mmHg before and
      142 +/- 13/87 +/- 7 mmHg after training. Clinic blood pressure decreased from 166
      +/- 14/103 +/- 5 mmHg to 157 +/- 12/99 +/- 6 mmHg (P < 0.03). Two-way analysis of
      variance indicated significant decreases in both glucose (P < 0.04) and insulin
      (P < 0.03), fasting and throughout the intravenous glucose tolerance test.
      CONCLUSIONS: Although mild exercise reduced clinic blood pressure significantly,
      it did not affect ambulatory blood pressure despite a marked reduction in glucose
      and insulin levels. This finding argues against a determinant role of insulin in
      the 24-h maintenance of blood pressure in hypertensive patients under the
      conditions of the study.

PMID- 8258678
TI  - A test of reproducibility of blood pressure and heart rate variability using a
      controlled ambulatory procedure.
AB  - OBJECTIVE: To determine whether the previously reported poor reproducibility of
      blood pressure variability measured by ambulatory blood pressure monitoring
      (ABPM) is due to the uncontrolled nature of physical and mental activity during
      the monitoring period. DESIGN: ABPM was performed on two separate days during
      which subjects performed identical activities, accompanied by the experimenter.
      Thus, activity and posture were controlled, both within and between subjects. Two
      measures of variability were used: SD and the root-mean-square of successive
      differences (RMSSD). METHODS: Thirty-seven subjects participated. Each engaged in
      a series of activities, such as walking outdoors, editing and alphabetizing
      tasks, and eating lunch, while wearing an A & D 2420 ambulatory blood pressure
      monitor which took measurements at 5-min intervals. Measures of variability were
      computed within each session. RESULTS: Contrary to previous reports,
      reproducibility was moderately high for blood pressure, with significant
      correlations between SD and between RMSSD for systolic and diastolic blood
      pressure. Heart rate reproducibility was less good. CONCLUSIONS: Lack of
      standardization of activities from one occasion to another is a major reason for
      the poor reproducibility of blood pressure variability when measured using ABPM.
      Even when activities are standardized, however, the reproducibility of blood
      pressure variability is still only moderate and may limit the ability of
      researchers to detect associations between ABPM variability and other measures.

PMID- 8258679
TI  - Prognostic value of 24-hour blood pressure variability.
AB  - OBJECTIVES: Evaluation of the prognostic value of 24-h blood pressure averages
      and 24-h blood pressure variability. DESIGN: After an initial thorough clinical
      and laboratory evaluation which included 24-h continuous ambulatory blood
      pressure monitoring, a group of hypertensive patients were re-examined after an
      average of 7.4 years. End-organ damage at the follow-up visit was related to
      different measures of blood pressure levels and variability obtained at the
      initial or the follow-up visit or both. METHODS: Seventy-three patients with
      essential hypertension of variable severity, in whom ambulatory blood pressure
      was monitored intra-arterially for 24 h (Oxford technique) were re-examined at a
      follow-up visit (including echocardiographic assessment of left ventricular mass
      index) 1-13 years later (mean 7.4 years). The severity of end-organ damage was
      quantified by a score and related to clinic blood pressure at follow-up and to
      (1) clinic blood pressure, (2) 24-h blood pressure mean, (3) 24-h short-term and
      long-term blood pressure variability, and (4) end-organ damage, all assessed at
      the initial visit (multiple regression analysis). RESULTS: The set of independent
      variables considered was significantly related to end-organ damage at follow-up
      (R = 0.51). The individual variables most important in determining end-organ
      damage at follow-up were clinic blood pressure at the follow-up visit (P < 0.01),
      the initial level of end-organ damage (P < 0.05) and long-term blood pressure
      variability (among half-hour standard deviation of 24-h mean blood pressure) at
      the initial evaluation (P < 0.05). The prognostic individual weight of the other
      haemodynamic parameters considered was less and not statistically significant.
      CONCLUSIONS: The results confirm that the level of blood pressure achieved by
      treatment and the degree of end-organ damage at the time of initial evaluation
      are important determinants of future end-organ damage related to hypertension.
      They also constitute the first longitudinal evidence that the cardiovascular
      complications of hypertension may depend on the degree of 24-h blood pressure
      variability.

PMID- 8258680
TI  - Circadian blood pressure variation in diabetic patients with autonomic
      neuropathy.

PMID- 8258681
TI  - Androgen-induced expression of the peripheral blood gamma delta T cell population
      in the chicken.
AB  - Unlike alpha beta T cells, the physiologic significance of gamma delta T cells
      has remained elusive. In avian species they comprise a large circulating T cell
      subset. Here we report that in chicken around the time of sexual maturation (4 to
      6 mo of age) a significant increase of the gamma delta T cells takes place in
      male but not in female chickens. The frequency of gamma delta T cells increases
      both in peripheral blood and spleen, but not in intestinal epithelium. This
      expansion is independent of MHC haplotype, being observed in various inbred and
      MHC-recombinant strains. Furthermore, administration of testosterone to young
      female chickens induces an equivalent increase in the frequency of gamma delta T
      cells in peripheral blood. These results indicate that sex, through androgens,
      has an effect on the gamma delta T cell numbers in a species, in which these
      cells form a major subset of peripheral lymphocytes.

PMID- 8258682
TI  - The majority of immature fetal thymocytes can be induced to proliferate to IL-2
      and differentiate into cells indistinguishable from mature natural killer cells.
AB  - Although immature thymocytes from day 14 embryonic mice (FTC) express IL-2R, they
      have generally been considered to be unresponsive to IL-2. We show here that they
      can in fact undergo substantial and prolonged growth in vitro provided that high
      doses of IL-2 are present. The ability of FTC to grow in IL-2 could be enhanced
      slightly by PMA and also by IL-4, but dramatically by the combination of IL-4 +
      PMA with IL-2. Pretreatment of FTC with IL-4 + PMA for as little as 24 h primed
      FTC for rapid and prolonged responsiveness to IL-2, permitting the establishment
      of long term lines. Kinetic and clonal analysis revealed that most individual FTC
      could grow under these conditions. Although proliferating cells expressed
      functional IL-2R of only very low affinity, and IL-2R alpha chains were
      undetectable by immunofluorescence, blocking experiments showed unambiguously
      that both IL-2R alpha and IL-2R beta were involved in signal transmission. FTC
      lines and clones developed in this manner lacked lineage-specific markers of
      mature T cells, B cells, and myeloid cells, but expressed the NK cell markers
      NK1.1 and asialo-GM1. They displayed potent cytolytic activity against NK
      sensitive targets, and, when stimulated with PMA+ionomycin, secreted IL-3 and IFN
      gamma, but not IL-2 or IL-4. After intrathymic injection they showed no evidence
      of growth or differentiation. These results demonstrate that most, if not all,
      immature thymocytes have the capacity to differentiate into cells which appear to
      be indistinguishable from mature NK cells. They suggest that T cells and NK cells
      derive from a common precursor which in the thymic environment differentiates
      into T cells and in the extrathymic environment into NK cells.

PMID- 8258683
TI  - Unexpected expansions of CD8-bearing cells in old mice.
AB  - As mice age, spontaneous changes occur in the receptor repertoire of their T
      cells. The receptor repertoire of CD4+ T cells does not change with age. By
      contrast, however, the percentage of alpha beta+, CD8+ T cells bearing particular
      V elements varies considerably between individual aged mice, although it is
      remarkably consistent among individual young animals within a given strain.
      Changes of receptor V element use among CD8+ T cells in individual mice are
      unpredictable. However, when a large number of mice of the same strain is
      analyzed, strain-specific trends in V element skewing are found. Old C3H.SW and
      B10.BR mice have mono- or oligoclonal expansions of CD8+ T cells. These
      expansions of peripheral CD8+ T cells with age are probably due to deregulation
      of proliferation of individual CD8+ T cells after recognition of viral or
      environmental Ag, accompanied, perhaps, by partial transformation of particular T
      cell clones. Another phenomenon documented herein is the fact that the CD4/CD8
      ratio drops steadily as a function of age. Shifts in CD4/CD8 ratio were not due
      to increased numbers of CD8+ T cells in spleen and lymph nodes, rather the CD4+ T
      cells disappeared from aging mice faster than CD8+ T cells.

PMID- 8258684
TI  - Down-regulation of macrophage transforming growth factor-beta messenger RNA
      expression by IL-7.
AB  - Transforming growth factor-beta (TGF-beta) is a potent inhibitor of immune
      responses. Macrophage-derived products, including TGF-beta, have been suggested
      as inhibitors of the antitumor immune response. We hypothesized that IL-7, a
      cytokine with antitumor properties, may exert its immunoregulatory effects in
      part through the down-regulation of TGF-beta. To test this hypothesis we analyzed
      IL-2-stimulated murine macrophage TGF-beta mRNA expression following exposure to
      IL-7 both in vitro and in vivo. IL-7 down-regulated IL-2-induced TGF-beta
      expression by macrophages in vitro, as well as after i.p. injections of IL-2 and
      IL-7 in vivo. The IL-7-mediated inhibition of TGF-beta mRNA expression did not
      require new protein synthesis and therefore appears to be a direct effect of IL
      7. IL-7 had no significant effect on the stability of TGF-beta mRNA. Nuclear run
      on assays revealed that the suppression of IL-2-induced TGF-beta gene expression
      by IL-7 is mediated at the level of transcription. Also, IL-7 decreased TGF-beta
      secretion as measured by bioassay. We conclude that IL-7 down-regulates TGF-beta
      and suggest that some of the proliferative and cytolytic activities mediated by
      cells exposed to IL-7 may be caused by a decrement in macrophage-derived TGF
      beta.

PMID- 8258685
TI  - Protein tyrosine kinase activation is required for lipopolysaccharide induction
      of cytokines in human blood monocytes.
AB  - Bacterial LPS induce production of cytokines such as IL-1, IL-6, and TNF in
      mononuclear phagocytes, and this represents a central component in the
      pathogenesis of septic shock syndrome. However, the mechanisms by which LPS
      activates these cells to express cytokines are not completely characterized. The
      present study addressed the role of different protein kinases in the LPS
      induction of cytokines. It is shown that LPS induced a 12- to 16-fold increase in
      IL-1 beta, IL-6, and TNF-alpha mRNA levels, and this was completely or more than
      80% blocked by the protein tyrosine kinase specific inhibitors herbimycin A and
      genistein at the concentrations of 1.7 and 37 microM, respectively. Protein
      kinase C inhibition by staurosporine reduced LPS induction of TNF-alpha, whereas
      it had no effects on IL-6 and IL-1 beta. Inhibition of protein kinase A by H89
      reduced IL-6 mRNA levels but did not detectably change IL-1 beta or TNF-alpha
      mRNA levels. In contrast, LPS did not increase leukemia inhibitory factor mRNA,
      which was constitutively expressed and not significantly reduced by these
      inhibitors. In addition to cytokine mRNA levels, LPS-induced IL-6 protein
      synthesis and IL-6 bioactivity were also reduced to baseline levels by the PTK
      inhibitors herbimycin A and genistein. Both PTK inhibitors also reduced the LPS
      activation of nuclear factor-kappa B (NF-kappa B), which is a transcription
      factor involved in the expression of cytokine genes such as IL-6 and TNF-alpha.
      The activation of NF-kappa B was also reduced by H89, whereas staurosporine had
      no effect on this response. In summary, these findings suggest that protein
      kinase C and protein kinase A appear to have selective effects in the LPS
      induction of cytokines, whereas PTK is required for LPS induction of a broad
      spectrum of cytokines and NF-kappa B activation in monocytes.

PMID- 8258686
TI  - Immunoglobulin secretion and phosphorylation of common proteins are induced by IL
      2, IL-4, and IL-6 in the factor responsive human B cell line, SKW6.4.
AB  - After the binding of IL-2, IL-4, or IL-6 to their respective receptors on
      activated human B cells, a multistep cascade of intracellular events is initiated
      that results in the secretion of Ig. However, it is not known whether these
      different cytokine receptors use common or divergent signal transduction pathways
      to stimulate Ig secretion. Therefore, we examined the signaling mechanisms used
      by a human lymphoblastoid cell line arrested at a late stage of differentiation,
      SKW6.4, that secretes IgM following stimulation with IL-2, IL-4, or IL-6 alone.
      Our study demonstrated that IL-2, IL-4, and IL-6-stimulation of IgM secretion by
      SKW6.4 cells was inhibited by either the serine/threonine kinase inhibitor, 1-(5
      isoquinolinesulfonyl)-2-methylpiperizine dihydrochloride (H7) or the tyrosine
      kinase inhibitor, genistein. To investigate the early phosphorylation events
      initiated by these cytokines, a membrane-enriched preparation from SKW6.4 cells
      was isolated in a manner that minimized the disruption of membrane protein
      complexes and then incubated with IL-2, IL-4, or IL-6 in the presence of [gamma
      32P]ATP. IL-2, IL-4, and IL-6 stimulated the rapid serine/threonine
      phosphorylation of 47-, 49-, and 91-kDa proteins. However, in contrast to the 47-
      and 49-kDa proteins that remained phosphorylated for up to 30 min
      poststimulation, the 91-kDa protein was rapidly dephosphorylated within 15 min of
      stimulation. The observation that serine/threonine phosphorylation of the same
      proteins was stimulated by IL-2, IL-4, and IL-6 suggested that the cytokines
      activated either different protein kinases with the same substrate specificity or
      the same protein kinase. In addition, stimulation of intact SKW6.4 cells with
      either IL-2, IL-4, or IL-6 induced the phosphorylation of two proteins with
      molecular masses of 45- to 50-kDa and 85 to 90-kDa. Taken together, our data
      demonstrate that activation of both a serine/threonine kinase and a tyrosine
      kinase is involved in the IL-2, IL-4, and IL-6-stimulation of IgM secretion by
      SKW6.4 cells and activation of the same or a similar serine/threonine protein
      kinase is an early step in the signal transduction pathway used by these
      cytokines.

PMID- 8258687
TI  - Nedocromil sodium selectively inhibits IgE and IgG4 production in human B cells
      stimulated with IL-4.
AB  - We studied the effect of nedocromil sodium (NES) on human IgE and IgG subclass
      production. NES inhibited IgE and IgG4 production, without affecting IgM, IgA,
      IgG1, IgG2, or IgG3 production, by IL-4-stimulated mononuclear cells (MNC)
      obtained from non-atopic donors. Inhibition of IgE and IgG4 production by NES
      required the compound to be added on day 0 and to be present throughout the
      entire period of culture. Inhibition of IgE and IgG4 production was not mediated
      by known inhibitors, including IFN-alpha, IFN-gamma, transforming growth factor
      beta, PGE2, or platelet-activating factor. Inhibition by NES required both T
      cells and monocytes because NES inhibited IgE production by B cells stimulated
      with IL-4 and anti-CD40 mAb in the presence, but not the absence, of T cells and
      monocytes. NES also inhibited IgE and IgG4 production in cultures stimulated with
      anti-CD3-treated T cells. However, in this case other isotypes were also
      inhibited by NES. In contrast to non-atopic donors' MNC, NES failed to inhibit
      spontaneous IgE and IgG4 production by MNC from atopic patients. However, NES was
      effective in inhibiting IL-4-induced IgE and IgG4 production in atopic patients'
      MNC without affecting IgM, IgA, IgG1, IgG2, or IgG3 production. NES inhibited IgE
      and IgG4 production by sIgE- and sIgG4-B cells, but not by sIgE+ and sIgG4+ B
      cells, respectively, stimulated with IL-4 or IL-4 plus anti-CD40 mAb in the
      presence of T cells and monocytes. These results suggest that NES may inhibit IL
      4-induced switching of IgE and IgG4 production by sIgE- B cells and sIgG4- B
      cells, respectively, by affecting the interaction of B cells, T cells, and
      monocytes.

PMID- 8258688
TI  - Anti-CD11b antibody prevents immunopathologic changes in viable moth-eaten bone
      marrow chimeric mice.
AB  - The effect of in vivo treatment with anti-CD11b (MAC-1) antibody (Ab) was
      examined in an inflammatory disease model, the viable moth-eaten (mev) mutant
      mouse. The autosomal recessive mev gene occurred spontaneously as a point
      mutation of the hematopoietic cell protein tyrosine phosphatase in C57BL/6 mice.
      Homozygotes (mev/mev) develop a chronic myelomonocytic inflammation, involving
      accumulation of myelomonocytic cells in lungs and skin, resulting in interstitial
      pneumonitis and severe edema in the paws. These mice also exhibit abnormalities
      in lymphoid development, thymic atrophy, with T cell and NK cell dysfunction.
      These inflammatory changes are transferrable by bone marrow cells of mev/mev
      mice, indicating that mev mutation is due to a stem cell defect in the
      myelomonocytic pathway. An anti-CD-11b (5C6) Ab inhibited the immunopathologic
      changes in the bone marrow chimeras, when the Ab treatment was initiated on day 
      1 or day 0 of the bone marrow transplant. The lungs, paws, and thymus all
      remained normal after treatment. Furthermore, the Ab also delayed the onset of
      the mev syndromes when the Ab was given 10 days after the bone marrow transfer.
      Therefore anti-CD11b Ab inhibited inflammation both prophylactically and
      therapeutically, and restored normal function of T and NK cells in this disease
      model. These results support the contention that CD11b molecules expressed in the
      myelomonocytic cells play a critical role in this naturally occurring
      inflammatory disease.

PMID- 8258689
TI  - Presentation of cytosolic antigen by HLA-DR requires a function encoded in the
      class II region of the MHC.
AB  - The processing pathway for the MHC class II-restricted presentation of endogenous
      cytosolic Ag is distinct from the class I pathway since a cytosolic form of the
      influenza virus A hemagglutinin, expressed by a recombinant vaccinia virus, was
      presented by HLA-DR in a B cell mutant lacking the TAP1 subunit of the
      transporter for Ag presentation (TAP). In this report, two additional B cell
      mutants have been used to define the requirements of this TAP1-independent
      processing pathway. The first mutant, .61, lacks expression of both TAP1 and TAP2
      genes, and of both LMP2 and LMP7 genes encoding proteasome subunits. As expected,
      class I-restricted presentation of the influenza virus matrix protein was totally
      deficient in mutant .61. In contrast, class II-restricted presentation of both
      the natural cytosolic matrix and the engineered cytosolic hemagglutinin proteins
      was functional in mutant .61. Thus, presentation of cytosolic Ag by class II
      molecules is independent of both TAP subunits and of the two MHC-encoded
      proteasome subunits. However, this endogenous processing pathway is dependent on
      at least one other function encoded in the class II region of the MHC as
      demonstrated with the second mutant, .174, in which a large deletion eliminates
      all expressed class II genes. Mutant .174 transfected with HLA-DR1 genes was
      previously shown to be defective in the presentation of exogenous Ag but normal
      in the presentation of short exogenous peptides. We show here that .174(DR1) is
      also defective in the presentation of cytosolic matrix and hemagglutinin
      proteins. This similar requirement for the class II-restricted presentation of
      either cytosolic Ag or internalized exogenous Ag suggests that both forms of Ag
      are ultimately targeted to the same cellular compartment for association with
      class II molecules.

PMID- 8258690
TI  - Triggering of the cytotoxic activity of murine natural killer and lymphokine
      activated killer cells through the NK2.1 antigen.
AB  - The NK2.1 alloantigen, one of the few NK-specific markers in the mouse,
      identifies a subset rather than all splenic NK cells. On the basis of the cell
      surface expression of a variety of Ag of the lymphocytic and monocytic lineages,
      we establish that BALB/c NK2.1+ cells are heterogeneous and that their phenotype
      is quite similar to the one reported for NK1.1+ cells. A NK2.1- cell population
      of the same size and related phenotype was also identified in fresh NK-enriched
      cell suspensions. After stimulation with IL-2, the only phenotypic trait that
      distinguishes NK2.1+ and NK2.1- cell subsets is precisely the expression of the
      NK2.1 Ag. To investigate whether NK2.1+ and NK2.1- lymphokine-activated killer
      cells would also be identical in their cytotoxic activity, NK-enriched spleen
      cells were cultured for 5 days with IL-2, sorted afterward on the basis of NK2.1
      expression, and compared for their capacity to lyse YAC-1 targets. NK2.1+ cells
      are significantly more lytic than NK2.1- cells, suggesting that the anti-NK2.1
      mAb, used for cell sorting, could have triggered NK2.1+ cells and enhanced their
      lytic activity. In support to this hypothesis we show that 1) immobilized anti
      NK2.1 mAb induces granule exocytosis by LAK cells, 2) soluble anti-NK2.1 mAb
      specifically inhibits NK and LAK cell-mediated lysis of 4LO3311 hybridoma cells
      secreting anti-NK2.1 mAb, and 3) binding of anti-NK2.1 mAb selectively enhances
      the lysis of NK-sensitive targets. Furthermore, the successful activation of
      NK2.1+ cells induced by anti-NK2.1 F(ab')2 or F(ab) mAb fragments indicates that
      the triggering mechanism is different from reverse antibody-dependent cellular
      cytotoxicity and does not require cross-linking of the NK2.1 molecule. Our
      results strongly suggest that the NK2.1 molecule is implicated in a post-binding
      NK cell signaling event, and point out the possible functional relevance of this
      NK-specific Ag in non-MHC-restricted cytotoxicity.

PMID- 8258691
TI  - Fc gamma RIIIA-mediated signaling involves src-family lck in human natural killer
      cells.
AB  - The cell surface receptor for IgG Fc domain (Fc gamma RIIIA, CD16) is present as
      a multimeric complex on human NK cells and is essential for antibody-dependent
      cellular cytotoxicity. Although CD16 engagement induces tyrosine phosphorylation
      of several substrates, the intracytoplasmic domains of the CD16 molecule lack
      intrinsic protein tyrosine kinase consensus sequences. We report here that, in
      human NK cells, engagement of the CD16 receptor induces tyrosine phosphorylation
      of p56lck tyrosine kinase. CD16 triggering through anti-receptor antibody
      enhances in vitro kinase activity of phosphotyrosyl proteins and
      autophosphorylation activity of anti-lck immunoprecipitates. Similar results were
      obtained after stimulation with IL-12. In vivo labeling experiments showed that
      CD16 cross-linking primarily induces in vivo phosphorylation of p56lck at the tyr
      394 autophosphorylation site. Using in vitro kinase assay of CD16
      immunoprecipitates from lysates of human NK cells, we demonstrated that a
      phosphorylated protein of 62 to 65 kDa was co-precipitated with CD16.
      Reprecipitation experiments also suggested that a small amount of p56lck may
      interact with this complex. These results indicate that CD16 triggering involves
      p56lck and that this kinase is therefore involved in the signaling pathways
      regulating NK cell cytolytic functions. However, additional kinases not yet
      identified are also likely to play a role in the early signaling events through
      CD16.

PMID- 8258692
TI  - Expression and function of mixed isotype MHC class II molecules in normal mice.
AB  - Mixed isotype MHC class II molecules (E alpha dA beta d) occur at extremely low
      levels on the surface of normal mouse B cells and macrophages, as determined by
      surface staining with an E alpha dA beta d-specific hamster mAb, H71-258.41. The
      surface levels of mixed isotype on the B cell lymphoma line A20 are approximately
      1 to 2% that of surface I-A, whereas the levels of these molecules on normal
      mouse B cells were estimated to be at least two to four times less than those on
      A20. Nevertheless, other investigators have recently reported that immunization
      of normal H-2d mice with the sperm whale myoglobin peptide 110-121 (SWM(110-121))
      elicits T cells, predominantly, V beta 8.2+, that recognize the peptide only in
      context of E alpha A beta. We have characterized a large number of SWM(110-121)
      specific T cell hybridomas from several strains of H-2d haplotype mice. All of
      the V beta 8.2+ 110-121-specific hybridomas were found to be restricted by E
      alpha dA beta d, whereas, of the V beta 8.2- 110-121-specific group,
      approximately half recognized the peptide through E alpha dA beta d whereas the
      remainder were restricted by either I-Ad or I-Ed. mAb inhibition experiments
      revealed that 14-4-4S (E alpha-specific) could block presentation by mixed
      isotype completely, while MK-D6 (A beta d-specific) and H71-258.41 (E alpha dA
      beta d-specific) only inhibited presentation when the concentration of peptide
      was limiting. Although A20 expresses very low levels of mixed isotype, 10 to 100
      nmol of the peptide produced a detectable response, illustrating the remarkable
      efficiency in presenting this peptide through E alpha dA beta d. The ability of
      normal mouse APC to use this restriction element despite its extremely low
      expression has important implications for the activation of T cells by low levels
      of peptide-MHC complexes.

PMID- 8258693
TI  - IFN-gamma and lipopolysaccharide differentially modulate expression of tumor
      necrosis factor receptor mRNA in murine peritoneal macrophages.
AB  - Expression of TNF receptor (TNFR) mRNA has been examined in murine peritoneal
      macrophages stimulated with LPS and/or IFN-gamma. LPS markedly enhanced
      expression of a heterogenous population of mRNA, which hybridized with a cDNA
      encoding the type II TNFR. mRNA expression was optimally induced by 4 to 8 h and
      returned to baseline by 24 h after stimulation. Interestingly, though IFN-gamma
      can synergize with LPS for the expression of TNF-alpha, it abrogated the LPS
      mediated enhancement of type II TNFR in a dose-dependent fashion. IFN-alpha,
      though less effective, had a qualitatively comparable effect. These effects were
      selective for the type II TNFR because levels of mRNA encoding the type I TNFR
      did not vary appreciably with any of the treatments described. The effects of IFN
      gamma on LPS-mediated TNFR expression were dependent on the sequence of exposure;
      pretreatment with IFN-gamma was most effective at blocking response to LPS,
      whereas IFN-gamma added 1 h after initiation of LPS treatment had little or no
      effect. The effects of both LPS and IFN-gamma on type II TNFR expression were
      mediated at least in part by modulation of transcription. The effects of both LPS
      and IFN-gamma were also independent of protein synthesis because inclusion of
      cycloheximide in the treatment protocol did not abrogate either the inductive or
      the suppressive effects. These findings suggest that IFN-gamma and LPS modulate
      the physiologic action of TNF through complex mechanisms involving effects on the
      transcription of TNF-alpha itself and on receptors through which it may act in
      autocrine or paracrine fashion.

PMID- 8258694
TI  - Comparative accessory cell function of human peripheral blood dendritic cells and
      monocytes.
AB  - The capacity of human peripheral blood (PB) dendritic cells (DC) and monocytes to
      facilitate T cell activation and the interaction molecules employed were
      compared. We have shown that precursors of DC constitute 2 to 3% of circulating
      PBMC, and can be isolated as CD33+CD14dim cells, whereas monocytes are
      CD33+CD14bright. Freshly obtained DC expressed similar densities of HLA-DR and
      the accessory molecules LFA-3, ICAM-1, and B7 as monocytes; after a 36-h
      incubation the expression of HLA-DR, ICAM-1, and B7 increased on both APC.
      Accessory cell function was examined in PB T cell cultures stimulated by
      suboptimal concentrations of immobilized mAb to CD3, and by stimulation of an
      allospecific T cell line. Freshly isolated monocytes and DC were comparable
      accessory cells in these assays, but their accessory function was increased by in
      vitro preincubation, although cultured DC and monocytes were comparably active.
      In contrast, DC were much more effective stimulators of freshly isolated
      allogeneic T cells than monocytes. DC were much more effective stimulators of
      freshly isolated allogeneic PB CD4+ naive and memory T cells than monocytes,
      whereas DC and monocytes were comparable accessory cells for memory and naive T
      cells stimulated with immobilized anti-CD3. The accessory molecules ICAM-1, LFA
      3, and B7 were used comparably by DC and monocytes for accessory function in the
      presence of immobilized anti-CD3 and in the MLR, and none was unique for either
      APC population. These accessory molecules costimulated T cells in an additive
      fashion. Although immature blood DC and monocytes expressed minimal B7 and did
      not utilize it as an accessory molecule, B7 played an important role in the
      increased accessory function of differentiated APC. The results indicate that PB
      DC and monocytes function most efficiently after differentiation into mature
      cells that express increased amounts of MHC and other accessory molecules.
      Because DC and monocytes exhibit comparable accessory function in anti-CD3 T cell
      stimulation, differences in the expression of MHC molecules and/or their bound
      peptides are likely to explain the markedly enhanced capacity of DC to stimulate
      allogeneic PB T cells.

PMID- 8258695
TI  - Predominant role of tumor necrosis factor-alpha in human monocyte IL-10
      synthesis.
AB  - In previous studies it has been shown that the bacterial endotoxin LPS induces an
      initial burst of inflammatory cytokine synthesis in human monocytes, which is
      followed by substantial IL-10 production; the IL-10 then down-regulates the
      inflammatory cytokine production as well as IL-10 production itself. Herein we
      tested the hypothesis that IL-10 production in human monocytes is under control
      of one of the cytokines induced by LPS. Accordingly, we cocultured purified human
      peripheral blood monocytes with a panel of cytokines including TNF-alpha, IL-1
      alpha, IL-1 beta, IL-6, granulocyte macrophage-CSF, transforming growth factor
      beta, and IFN-alpha and then measured IL-10 mRNA production using a
      semiquantitative reverse transcription-polymerase chain reaction technique. We
      found that TNF-alpha had a major effect on IL-10 mRNA production, inducing a 20-
      to 120-fold increase over baseline production. In contrast, IL-1 alpha, IL-1
      beta, IL-6, granulocyte macrophage-CSF, transforming growth factor-beta, and IFN
      alpha had little effect (< 3-fold). The induction of IL-10 mRNA by TNF-alpha in
      monocytes was dose dependent and began between 8 and 24 h after the addition of
      TNF-alpha; this suggests that the increased IL-10 mRNA level was due to de novo
      mRNA synthesis rather than mRNA stabilization; this latter finding was
      corroborated by actinomycin-D time course studies, which showed that the half
      life of IL-10 was less than 1 h and was not significantly altered by TNF-alpha.
      These studies concerning IL-10 mRNA induction by TNF-alpha were corroborated by
      studies of IL-10 protein secretion: TNF-alpha alone, but not IL-1 alpha, IL-1
      beta, or IL-6 induces substantial IL-10 secretion. Furthermore, LPS induces a
      large amount of IL-10 secretion that is largely inhibited (50 to 75%) by anti-TNF
      alpha but not by antibodies to other inflammatory cytokines. Finally, TNF-alpha
      augments LPS-induced IL-10 secretion. Taken together, these findings suggest that
      TNF-alpha is unique among the inflammatory cytokines in its role as an inducer of
      IL-10 in human monocytes, as such, it induces a molecule that provides negative
      feedback to its own production.

PMID- 8258696
TI  - IL-2 stimulation of T lymphocytes induces sequential activation of mitogen
      activated protein kinases and phosphorylation of p56lck at serine-59.
AB  - p56lck, a member of the src family of non-receptor protein tyrosine kinases, is
      expressed almost exclusively in cells of lymphoid origin. p56lck is known to
      associate with the T lymphocyte surface glycoproteins CD4 and CD8, and plays a
      critical role in both T lymphocyte development and activation. p56lck also
      associates with the beta-subunit of the IL-2R, and is activated when IL-2 binds
      to its receptor. Using primary cultures of Con A-activated normal splenic mouse T
      lymphocytes, we observed an IL-2-induced sequence of events involving p56lck. We
      saw a rapid (within 1 to 2 min) and transient increase in p56lck kinase activity,
      which preceded the activation of both the p42erk-2 and p44erk-1 mitogen-activated
      protein kinases, maximal activation of which was observed after 10 min. We also
      observed an IL-2-induced shift in the electrophoretic mobility of p56lck from an
      apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck), which reached a
      maximum at 15 min, the level of p60lck remaining constant for up to 4 h
      thereafter. This IL-2-induced shift correlated with the phosphorylation of serine
      59 of p56lck, a site that mitogen-activated protein kinases are capable of
      modifying in vitro. The implications of these results for the understanding of
      both p56lck function and lymphoid cell receptor signaling pathways are discussed.

PMID- 8258698
TI  - Structure and genomic organization of immunoglobulin light chain in the channel
      catfish. An unusual genomic organizational pattern of segmental genes.
AB  - Channel catfish L chain cDNA was obtained through a PCR strategy and used to
      isolate multiple L chain clones from cDNA and genomic libraries. Sequence
      analysis of full-length cDNA indicates that the V region is preceded by a leader
      peptide, and represented by framework and CDR regions. Both VL and CL domains
      contain the invariant cysteines and tryptophans as well as other phylogenetically
      conserved L chain residues. The sequence similarity of the catfish L chain with
      higher vertebrate kappa- and lambda-chains, however, does not readily allow the
      catfish L chain to be classified. Eight cDNA clones isolated from a cDNA library
      were shown to represent different processed derivatives of sterile L chain
      transcripts. These transcripts share a similar upstream sequence region and
      extend downstream to include a CL or alternatively a JL segment in partial germ
      line configuration that has been spliced into a CL. Sequence comparisons indicate
      that these transcripts represent the product of different L chain loci. Genomic
      Southern blot analyses with VL and CL probes indicate that there are at least 30
      VL segments and at least 15 CL segments. The analysis of 17 genomic L chain
      clones showed that each hybridized with VL-, JL-, and CL-specific probes.
      Characterization of the gene segments in three of these clones indicates a
      previously undescribed pattern of segmental gene organization. Gene segments are
      found in clusters with VL, JL, and CL segments in each cluster. Within a cluster
      VL segments reside upstream of single copies of closely linked JL and CL
      segments. The proximity of VL segments downstream from JL-CL segments suggests
      that individual clusters may be closely linked. The VL segments are located in
      opposite transcriptional polarity relative to the JL and CL gene segments, which
      indicates that VL segments are likely rearranged to JL-CL segments by inversion
      rather than deletion events.

PMID- 8258697
TI  - Specific induction of 80-kDa tumor necrosis factor receptor shedding in T
      lymphocytes involves the cytoplasmic domain and phosphorylation.
AB  - The 80-kDa TNFR (TNFR80) expressed by activated human T cells is constitutively
      phosphorylated and undergoes limited proteolytic cleavage (shedding) at the cell
      surface releasing a 40-kDa soluble TNF-binding protein. Triggering of activated T
      cells through the TCR rapidly increased the rate of TNFR80 shedding > 20-fold
      more than nonstimulated cells, demonstrating that shedding is a specific,
      inducible process. The protein kinase inhibitor staurosporine inhibited
      constitutive phosphorylation and blocked inducible shedding of TNFR80, suggesting
      that phosphorylation may be important for cleavage of the extracellular domain.
      However, a deletion mutation of the entire cytoplasmic domain of human TNFR80 was
      shed when expressed in murine L929 cells, albeit relatively poorly compared with
      full length receptor. This demonstrates that the cytoplasmic domain is important
      but not essential for cleavage of the extracellular domain of TNFR80. Moreover, a
      requirement for phosphorylation of proteins other than the receptor was revealed
      by the finding that staurosporine completely blocked cleavage of the cytoplasmic
      deletion mutant. Collectively, these results demonstrate that protein
      phosphorylation is essential and the cytoplasmic domain is important for
      regulating the inducible production of soluble TNF-binding proteins by activated
      effector T cells.

PMID- 8258699
TI  - Isolation of a cDNA encoding thymic shared antigen-1. A new member of the Ly6
      family with a possible role in T cell development.
AB  - We have previously characterized a novel mouse thymocyte marker, defined as
      thymic shared Ag-1 (TSA-1), present on both immature thymocytes and a subset of
      thymic medullary epithelial cells. MTS 35, a mAb specific for TSA-1, alters T
      cell differentiation when added to fetal thymic organ cultures, suggesting TSA-1
      may be important for T cell development in the thymus. In this study, we describe
      the isolation of a cDNA encoding TSA-1 using transient expression of COS-7 cells
      and selection with MTS 35. The predicted amino acid sequence of this cDNA encodes
      a 15 to 17-kDa protein and the expressed protein is linked to the membrane via a
      phosphatidylinositol moiety. TSA-1 is transcriptionally active at various levels
      in all organs examined, suggesting that its role is not solely intrathymic. TSA-1
      shares amino acid sequence homology to the mouse Ly6 multigene family, epidermal
      growth factor-like receptors, and to cobra venom neurotoxin. The Tsa-1 locus is
      located on chromosome 15 linked to Ly6 on the mouse genome. We also examined the
      effects of MTS 35 in fetal thymic organ cultures repopulated with two subsets of
      thymocytes representing defined stages of T cell development. Our results suggest
      that TSA-1 may play a role during positive selection and the transition from
      CD4+CD8+ thymocytes to the mature CD4+CD8- and CD4-CD8+ subsets.

PMID- 8258700
TI  - Comparative analysis of the kinetics of binding and internalization of IL-5 in
      murine IL-5 receptors of high and low affinity.
AB  - The high affinity IL-5R consists of at least two chains, alpha and beta. IL-5R
      alpha binds IL-5 with low affinity. IL-5R beta is required to construct the high
      affinity IL-5R, although IL-5R beta does not bind IL-5 by itself. To characterize
      the roles of IL-5R alpha and IL-5R beta on the association, dissociation, and
      internalization of IL-5, we compared the binding kinetics and the internalization
      of 35S-labeled IL-5 by high affinity IL-5R (dissociation constant approximately
      150 pM) bearing T88-M with those by low affinity IL-5R (dissociation constant
      approximately 30 nM) bearing MOPC104E. We found that association kinetics of IL-5
      to either natural receptor were similar. The maximal binding of IL-5 to both high
      and low affinity IL-5R was rapid (within 10 min). The dissociation of IL-5 from
      low affinity IL-5R was rapid (t1/2 < 30 min), but that from the high affinity IL
      5R was remarkably slower (t1/2 > 120 min). The internalization of IL-5 was
      observed only in T88-M, but not in MOPC104E, suggesting that IL-5 internalization
      is mediated via high affinity IL-5R. Association and dissociation kinetics
      observed in natural cell line were mostly reproduced by the kinetic analysis of
      reconstituted IL-5R on transfectants with either the IL-5R alpha or the IL-5R
      alpha and IL-5R beta genes. However, transfectants that expressed IL-5R alpha
      significantly internalized IL-5, although the level was much lower than observed
      with IL-5R alpha beta transfectants. These results suggest that IL-5R alpha may
      be involved in the internalization of IL-5, whereas IL-5R beta is responsible for
      slowing the dissociation and the efficient internalization of IL-5 by stabilizing
      the ligand-receptor complex.

PMID- 8258701
TI  - Characterization of an IgM Fc-binding receptor on human T cells.
AB  - The existence of an IgM receptor on human T cells has been suggested by T cell
      rosetting with IgM-coated erythrocytes. In this study we used
      immunofluorocytometry to demonstrate that 1) after short-term culture, a majority
      of the T cells can bind IgM at easily detectable levels, 2) human and mouse IgM
      preparations bind to human T cells but other Ig isotypes do not, 3) the IgM
      binding is saturable and inhibitable only by Ig of IgM isotype and 4) the Fc
      portion of IgM is involved in the binding to a protease-sensitive cell surface
      protein. Biochemical analysis of the T cell receptor for IgM reveals a cell
      surface protein of 60 kDa in comparison with the 58 kDa Fc mu receptors (Fc mu R)
      on B-lineage cells. Although Fc mu R expression is up-regulated after B cell
      activation, the reverse is true after T cell activation. In addition, the T cell
      Fc mu R is relatively resistant to phospholipase C treatment. These results
      indicate that T- and B-lineage cells express Fc mu R with different biologic
      characteristics.

PMID- 8258702
TI  - Class II MHC transcriptional mutants are defective in higher order complex
      formation.
AB  - Human class II MHC genes are regulated in part by a series of conserved upstream
      sequence elements termed the X1, X2, and Y boxes. Class II MHC transcriptional
      mutant B cell lines have been defined that differ with regard to the presence of
      RFX, an X1 box DNA-binding activity. To further characterize these mutant cell
      lines, we tested the ability of these conserved upstream elements to respond to
      the presence of known transcriptional activation domains. A series of HLA-DRA
      promoter reporter constructions carrying Gal4 binding sites and GAL4 fusion
      protein expression vectors were cotransfected into both wild type B cells and
      mutant B cells representing the two RFX phenotypes. Regardless of RFX or class II
      phenotype, the activation domains of GAL4-VP16 and GAL4-E1a could synergistically
      stimulate expression of constructions containing both the X2 and Y boxes. GAL4
      VP16- and GAL4-E1a-mediated expression was inhibited by the presence of the X1
      box in cells that contained RFX. In mutant cells that lacked RFX, GAL4-VP16
      activation was not inhibited. In the RFX-positive class II mutant cell line
      RJ2.2.5, the X1 box inhibitory activity could be overcome by separating the Gal4
      site from the X1 box by two additional helical turns, suggesting that the RFX
      factor is bound at the X1 site and sterically interferes with activation. This
      was not the case in wild type B cells, suggesting that a stable higher order
      complex forms in wild type cells and not in the mutant cells.

PMID- 8258703
TI  - Inhibitors of poly(ADP-ribose) polymerase increase antibody class switching.
AB  - Previous studies suggest that heavy chain isotype switch (S) recombination is
      directed by cytokine-induced transcription of the unrearranged CH gene before
      recombination. In studies aimed at identifying other signaling pathways that
      promote switching, we discovered that inhibitors of the nuclear enzyme poly(ADP
      ribose) polymerase (PARP) increase LPS-induced switching to IgA in the B cell
      lymphoma 1.29 mu and to IgG1 in LPS + IL-4-treated splenic B cells. PARP, which
      binds to and is activated by DNA strand breaks, catalyzes the removal of ADP
      ribose from NAD+ and poly(ADP-ribosylation) of chromatin-associated acceptor
      proteins. This enzyme is believed to function in cellular processes involving DNA
      strand breaks as well as in modulating chromatin structure. In 1.29 mu cells,
      PARP inhibitors increase IgA switching by day 2 and cause a fivefold increase in
      switching on day 3 as assayed by immunofluorescence microscopy. In spleen B
      cells, the PARP inhibitor nicotinamide increases IgG1 switching by about twofold.
      Nicotinamide also causes a reduced intensity of hybridization of C mu- and C
      alpha-specific probes to genomic DNA fragments containing the expressed VDJ-C mu
      and the unrearranged S alpha-C alpha segments, respectively, in 1.29 mu cells,
      indicating that PARP inhibition increases rearrangement of these fragments.
      Induction of switching by PARP inhibitors is not mimicked by treatment with cAMP
      analogues or reduced by inhibitors of protein kinase A. Induction of switching by
      PARP inhibitors does not appear to involve increased levels of transcription of
      the unrearranged C alpha gene.

PMID- 8258704
TI  - Polymorphism in BoLA-DRB3 exon 2 correlates with resistance to persistent
      lymphocytosis caused by bovine leukemia virus.
AB  - The relationship between polymorphism of the bovine lymphocyte Ag (BoLA)-DRB3
      gene and resistance and susceptibility to persistent lymphocytosis (PL) caused by
      bovine leukemia virus (BLV) was investigated. Exon 2 of the BoLA-DRB3 gene was
      cloned from animals with BoLA haplotypes previously found to be associated with
      resistance and susceptibility to PL. Sequence analysis revealed the presence of
      the amino acids Glu-Arg (ER) at putative Ag binding residues 70 and 71 only in
      BoLA haplotypes associated with resistance to PL. This correlation was confirmed
      in a case control study (n = 26) using an allele-specific polymerase chain
      reaction for the detection of ER at residues 70-71. These results provide a
      molecular basis for Ir gene control of resistance and susceptibility to PL and
      suggest that the cellular immune response is important in preventing the in vivo
      spread of BLV infection.

PMID- 8258705
TI  - Pyrrolidine dithiocarbamate inhibits NF-kappa B mobilization and TNF production
      in human monocytes.
AB  - The human TNF promoter contains four potential nuclear factor-kappa B (NF-kappa
      B)-binding sites, with the strongest binding seen for the -605 motif. Nuclear
      extracts from unstimulated cells of the human monocytic cell line, Mono Mac 6,
      contain one specific binding protein (complex II), consistent with a constitutive
      p50 homodimer. Stimulation of Mono Mac 6 cells with LPS will increase complex II
      and will strongly induce a second specific complex (complex I), which represents
      the p50/65 heterodimer. Treatment of Mono Mac 6 cells with pyrrolidine
      dithiocarbamate (PDTC) at 300 microM will block the LPS-induced complex I almost
      completely and will reduce complex II to the constitutive level. Binding activity
      of other nuclear factors that recognize the SP-1 and c/EBP motifs of the human
      TNF promoter is not affected by such treatment. Northern blot analysis
      demonstrates that PDTC treatment will strongly reduce LPS-induced TNF
      transcripts. Secreted TNF protein as detected in the Wehi 164S/ActD bioassay and
      in a sandwich immunoassay was similarly reduced by PDTC. Kinetic analyses show
      that after LPS stimulation, NF-kappa B will peak at 1 h, TNF transcript
      prevalence at 2 h, and TNF protein at 4 h. PDTC did not shift this response to
      LPS to a later time, but suppressed NF-kappa B mobilization, TNF transcripts, and
      TNF protein over the entire 8-h observation period. Analysis of freshly isolated,
      LPS-stimulated blood monocytes showed a similar blockade of NF-kappa B.
      Furthermore, in these primary cells, induction of TNF transcripts, as determined
      by Northern blot analysis and by quantitative polymerase chain reaction, was
      prevented by PDTC as was TNF protein production. These data show that
      dithiocarbamates can profoundly affect cytokine expression and suggest that NF
      kappa B is involved in LPS-induced TNF gene expression in human monocytes.

PMID- 8258706
TI  - Inhibition of C3 and IgG proteolysis enhances phagocytosis of Porphyromonas
      gingivalis.
AB  - In the face of an apparently competent immune response to Porphyromonas
      gingivalis, it is unclear how P. gingivalis evades the immune response and
      persists in human periodontitis. Particularly germane may be its ability to
      resist phagocytosis by degrading and not binding serum opsonins. In our study,
      the resistance by invasive (W83 and A7436) and noninvasive (ATCC 33277) P.
      gingivalis strains to phagocytosis by human neutrophils was compared with their
      C3- and IgG-proteolytic activity. The ability of opsonic human serum antibody to
      inhibit C3 proteolysis was also evaluated. Our results indicate that the more
      phagocytosis-resistant invasive strains accumulate less 125I-C3 than the
      noninvasive strain; moreover, invasive strains degrade complement C3 in a dose
      dependent manner, inhibitable by rabbit antiserum or adult periodontitis serum.
      Opsonization and C3 accumulation on strain A7436 were both facilitated by
      pretreatment with rabbit antiserum, certain adult periodontitis sera, protease
      inhibitors (p-chloromercuriphenylsulfonic acid, N alpha-p-tosyl-L-lysine
      chloromethyl ketone, diisopropylfluorophosphate), heat (60 degrees C, 15 min),
      and were Mg2+ dependent. The sera from 13 human subjects with or without
      periodontitis were assayed for antibody titers to P. gingivalis (ELISA units),
      opsonic activity (% of PMN engaged in phagocytosis) and enhancement of C3
      accumulation. Statistically significant associations were observed between % of
      PMN engaged in phagocytosis and % C3 accumulation, between % of PMN engaged in
      phagocytosis and ELISA units and between % C3 accumulation and ELISA units.
      Degradation of purified rabbit IgG, but not specific antibody-containing rabbit
      IgG by P. gingivalis A7436 was observed, and was inhibited by diisopropyl
      fluorophosphate (DFP) or cold (2 degrees C). Our data suggest that C3 and IgG
      cleavage by P. gingivalis proteases are inhibitable by antibody and are
      contributory factors in, but are not the sole determinants of, phagocytosis
      resistance.

PMID- 8258707
TI  - T cells are responsive to the simian virus 40 large tumor antigen transgenically
      expressed in pancreatic islets.
AB  - The qualities of a peripheral Ag that determine whether T cells will be tolerant
      of or responsive to it are poorly understood. To approach this problem, we
      studied the T cell response in a line of transgenic mice selectively expressing
      an oncoprotein in the islets of Langerhans. The SV40 large tumor Ag (SV40-T) is
      directed to islet beta-cells in Rip1-Tag3 (RT3) mice by a hybrid insulin promoter
      SV40-T construct. Ag is first detected on these cells between 10 and 12 wk after
      birth. RT3 mice were bred with mice expressing a transgenic rearranged TCR
      recognizing SV40-T in the context of the class I MHC molecule, H-2Kk. T cell
      response in the resultant RT3/TCR-double transgenic mice was then analyzed. T
      cells are fully responsive to SV40-T in RT3/TCR-transgenic mice, and T cells
      infiltrate the islets of both RT3 and RT3/TCR-transgenic mice. This work
      demonstrates that T cells may remain responsive to self-Ag expressed outside the
      thymus, and that this responsiveness may result in autoimmunity. The
      developmentally delayed expression or the oncogenic nature of SV40-T in the RT3
      transgenic mice may be important in determining this T cell response.

PMID- 8258708
TI  - Kinetic analysis of antigen-specific immune responses in resistant and
      susceptible mice during infection with Trypanosoma cruzi.
AB  - The Tulahuen strain of Trypanosoma cruzi has been shown previously to cause
      higher parasitemias and greater mortality in BALB/c mice compared with C57BL6/J
      mice. The goal of our study was to determine whether different cytokine responses
      to parasite Ag during T. cruzi infection correlate with the susceptible and
      resistant phenotypes identified in these mice. At several time points after
      initial infection with insect-derived metacyclic trypomastigotes, lymph node and
      spleen cell suspensions were prepared from animals of each mouse strain. These
      lymphocyte suspensions were stimulated with Ag prepared from cultured parasites
      and the production of IFN-gamma, IL-4, IL-2, and IL-5 was measured. Lymphocytes
      from C57BL6/J mice produced 10-fold more IFN-gamma than BALB/c lymphocytes.
      However, this enhanced response occurred only for a limited time preceding peak
      parasitemias. Ag-induced secretion of IL-4 from BALB/c lymphocytes was detectable
      by 2 wk of infection and increased during the 2nd and 3rd mo of infection. Most
      C57BL6/J culture supernatants did not contain measurable levels of IL-4.
      Lymphocytes from both murine strains produced levels of IL-2 and IL-5
      indistinguishable from uninfected controls. These results indicate that increased
      numbers or potency of lymphocytes that produce Ag-specific IFN-gamma responses
      are present in resistant mice during T. cruzi infection. This phenomenon may be
      responsible for the lower parasitemias seen in C57BL6/J mice. However, even these
      relatively resistant mice become chronically infected with T. cruzi, and spleen
      cells from infected mice can suppress IFN-gamma induced by heterologous Ag. Our
      data suggest that IL-4 production is a marker for the T. cruzi susceptible
      phenotype. Differential production of IL-2 or IL-5 was not found, suggesting that
      these cytokines are not important factors in T. cruzi resistance or
      susceptibility.

PMID- 8258709
TI  - Granuloma eosinophils enhance IL-5 production by lymphocytes from mice infected
      with Schistosoma mansoni.
AB  - IL-5 is essential for granuloma eosinophilia in mice infection with
      schistosomiasis. The granulomas constitutively make IL-5 that originates from
      granuloma CD4+ T lymphocytes. This observation prompted us to learn whether non-T
      cell elements in the granuloma can promote constitutive IL-5 production. Neither
      granuloma eosinophils nor spleen cells from infected mice constitutively produced
      detectable levels of IL-5. Yet, mixing spleen cells with granuloma eosinophils
      resulted in spontaneous IL-5 secretion without promoting IL-4 production.
      Moreover, the admixed cultures were more responsive to anti-CD3 or soluble egg Ag
      than were cultures containing spleen cells alone. IL-5 ELISPOT assays in
      Transwell chambers showed that the cellular origin of IL-5 in the admixed
      cultures was the spleen cells, and that the phenomenon did not require cell-to
      cell contact with granuloma eosinophils. Also, admixed cultures of granuloma
      eosinophils and spleen cells released less IL-5 in the presence of mAb that
      specifically blocked the biologic activity of either IL-2, IL-2R, or IAk.
      However, adding rIL-2 to spleen cell cultures at concentrations up to 100 U/ml
      could not stimulate secretion of IL-5. Because eosinophil supernatants contained
      no IL-2 as assessed by CTLL-2 bioassay, the release of IL-5 in response to
      eosinophils was not likely secondary to eosinophil secretion of IL-2. Thus, it
      appears that eosinophils produce a soluble substance that, with IL-2 and ongoing
      class II MHC/TCR interaction, enhances lymphocyte IL-5 output.

PMID- 8258710
TI  - Characterization of a C3 receptor on the envelope of Schistosoma mansoni.
AB  - The surface of the syncytial epithelium of the human parasite, Schistosoma
      mansoni, consists of an apical plasma membrane (APM) and an overlying envelope
      (En). The rapid turnover of these membranes is an adaptation to parasitism and is
      influenced by ambient signals emanating from the host's immune system. The third
      component of complement (C3) has been shown to stimulate the synthesis of the En
      via a C3-binding protein (C3bp) and a Ca(2+)-dependent signal transduction
      mechanism. Using ELISA the C3bp was found to be restricted to the En. In
      addition, cross-linking of iodinated C3 to En proteins with the homobifunctional
      noncleavable disuccinimidyl suberate reagent yielded a receptor-C3 complex in
      excess of 250 kDa, and SDS-PAGE analysis of solubilized En proteins that were
      radiolabeled and chromatographed on C3-Sepharose revealed a 130-kDa protein that
      specifically bound to the C3 beads. In further experiments, using a
      photoactivatable radiolabeled cross-linker, the Denny-Jaffe reagent, C3
      transferred the radiolabel to a 130-kDa En protein. Metabolic labeling
      experiments have demonstrated that this C3bp is synthesized by the parasite and,
      more importantly, antibodies raised against the C3bp blocked En synthesis in
      vivo. Also, the surface localization of the C3bp was demonstrated using
      immunolabeling electron microscopy. The data presented herein strongly suggest
      that the 130-kDa schistosome En protein is a C3bp responsible for renewal of the
      En in response to C3 binding.

PMID- 8258711
TI  - Mycobacteria-macrophage interactions. Macrophage phenotype determines the
      nonopsonic binding of Mycobacterium tuberculosis to murine macrophages.
AB  - During tuberculosis, host defenses may be determined, in part, by the capacity of
      resident, elicited, and activated macrophages to bind and ingest Mycobacterium
      tuberculosis. We have investigated the mechanism by which macrophages bind M.
      tuberculosis and other mycobacteria in a serum-free system. The extent of binding
      of M. tuberculosis to macrophages was dependent on the phenotype of the
      macrophage; thioglycollate-elicited and immune-activated macrophages bound
      mycobacteria poorly, whereas resident macrophages bound mycobacteria efficiently.
      Within 'freshly' explanted macrophage populations (from 2 to 24 h in vitro) poor
      binding of mycobacteria correlated with poor binding of C3bi-coated particles,
      but not with variations in the level of complement receptor 3 (CR3) expression.
      Induction of C3bi-coated particle binding in thioglycollate-elicited macrophages
      by PMA was not accompanied by enhanced M. tuberculosis binding. Inhibition of M.
      tuberculosis binding by resident macrophages could only be achieved using a mAb
      recognizing an epitope within CR3 distinct from that which recognizes C3bi. Our
      results suggest that nonopsonic binding of M. tuberculosis is mediated by a site
      within CR3, which is distinct from the C3bi binding site. In addition, we show a
      variation in the capacity of different macrophage phenotypes to bind mycobacteria
      nonopsonically. These data suggest that heterogeneity in macrophage-mediated
      clearance of M. tuberculosis may be a significant factor in the progression of
      tuberculosis.

PMID- 8258712
TI  - Role of adjuvants in the modulation of antibody isotype, specificity, and
      induction of protection by whole blood-stage Plasmodium yoelii vaccines.
AB  - Mice were immunized with whole killed blood stage Plasmodium yoelii parasites in
      15 adjuvant formulations then boosted and challenged with parasitized blood. Five
      of six groups immunized with the Ag in oil-in-water emulsions or formulations
      without oil were protected. Formulations that induced protection contained
      saponin, pertussis, copolymer P1004, and detoxified RaLPS. In contrast, none of
      nine groups of animals immunized with Ag in water-in-oil emulsions were
      protected. Ineffective adjuvants included CFA and water-in-squalene emulsions
      with copolymer L141 plus detoxified RaLPS, dimethyldioctadecyl ammonium bromide,
      and mycobacterial cell wall skeletons. Antibody was measured by ELISA against
      disrupted parasites and by indirect fluorescent antibody (immunofluorescence)
      using intact parasites. Protection was associated with antibody of the IgG2a
      isotype detected by immunofluorescence but not with other isotypes detected by
      immunofluorescence or any type antibody detected by ELISA. The water-in-oil
      adjuvants induced high titers by ELISA but low titers by immunofluorescence.
      These results, together with Western blot analyses, suggested that adjuvant
      vehicles control the specificity of antibody and that this, in turn, is essential
      for induction of protective immune responses in this model.

PMID- 8258713
TI  - IFN inhibits inflammatory responses and protective immunity in mice infected with
      the nematode parasite, Nippostrongylus brasiliensis.
AB  - Mice infected with the gastrointestinal nematode parasite Nippostrongylus
      brasiliensis (Nb) develop responses associated with enhanced production of IL-4
      (increased serum IgE levels and intestinal mucosal mastocytosis) and IL-5 (tissue
      and peripheral blood eosinophilia). The antagonistic effects of IFN on IL-4
      mediated responses prompted an examination of the effects of IFN on the host
      response to Nb. Treatment with rIFN-alpha and rIFN-gamma induced a marked
      increase in parasite egg production (fecundity) in BALB/c mice infected with Nb
      and delayed intestinal expulsion of adult worms. Treatment with rIFN-alpha or
      rIFN-gamma also inhibited the rise in peripheral blood eosinophilia that follows
      inoculation with Nb, and the intensity of pulmonary perivascular tissue
      eosinophilia. However, Nb-induced increases in serum IgG levels and intestinal
      mastocytosis were only temporarily delayed by IFN. Induction of endogenous IFN
      production by injection of fixed Brucella abortus into mice infected with Nb also
      resulted in an increased worm fecundity and delayed adult worm expulsion. These
      effects were ablated when mice given Brucella abortus also received injections of
      neutralizing anti-IFN antibodies. Thus, IFN inhibit host protective immunity to
      Nb, perhaps by interfering with the production and effects of Th2 cytokines.

PMID- 8258714
TI  - T cells bearing V beta 6 T cell receptors in the cell-mediated immune response to
      Mycobacterium leprae.
AB  - The skin lesions of leprosy provide a window into the immunoregulatory events
      involved in the human immune response to infection. T cells are thought to play a
      vital role in the pathogenesis of different forms of the disease. To identify
      predominant specific T cell subpopulations in leprosy lesions, the TCR-beta chain
      repertoire was simultaneously studied in skin biopsy specimens and PBMC from both
      immunologically resistant tuberculoid leprosy and susceptible lepromatous leprosy
      patients. This was accomplished by obtaining RNA from lesions and PBMC,
      synthesizing cDNA, and performing the polymerase chain reaction. We found that
      TCR gene subfamilies V beta 6.1 through V beta 6.4 (V beta 6.1-4) were strikingly
      overrepresented in lesions vs PBMC of seven of nine tuberculoid patients but only
      one of nine lepromatous patients. Similarly, V beta 6.5/6.8/6.9 subfamilies were
      predominant in four of nine tuberculoid patients, but none of the nine
      lepromatous patients. To explore the influence of the complementarity-determining
      region 3 (CDR3) in selection of T cells expressing V beta 6 TCR, we sequenced the
      V beta 6.1-4-C beta polymerase chain reaction products derived from the lesions
      and PBMC of two tuberculoid patients. From the analysis of deduced amino acid
      sequences, we found conserved amino acid residues and amino acid motifs in the
      CDR3 region of the lesion-derived sequences from each patient. Our data suggest
      that the nominal Ag select T cells bearing V beta 6 TCR in the cell-mediated
      immune response to Mycobacterium leprae.

PMID- 8258715
TI  - Induction of porcine granulocyte-mediated tumor cytotoxicity by two distinct
      monoclonal antibodies against lytic trigger molecules (PNK-E/G7).
AB  - PNK-E and G7 mAb bind to distinct porcine granulocyte function-associated
      molecules and induce granulocyte-mediated cytotoxicity against tumor targets. PNK
      E mAb binds to a 205-kDa molecule that reduces to a dispersed band of 50 kDa on
      SDS-PAGE analysis. Previous work demonstrates that G7 mAb immunoprecipitates a
      molecule that appears as a heterodispersed 40-kDa band under both reducing and
      nonreducing conditions on SDS-PAGE analysis. Whole but not F(ab')2 PNK-E and G7
      mAb induce dose-dependent porcine granulocyte-mediated lysis of FcR+ but not FcR-
      targets, suggesting a redirected cytotoxicity mechanism of granulocyte-mediated
      killing. Fresh porcine granulocytes also mediate significant levels of antibody
      dependent cellular cytotoxicity (ADCC) against nucleated (SB) target cells.
      Neither whole nor F(ab')2 PNK-E mAb affects granulocyte-mediated ADCC against SB
      target cells. However, both whole and F(ab')2 G7 mAb inhibit granulocyte-mediated
      ADCC against SB targets by approximately 50%. Bound F(ab')2 G7 mAb inhibits PNK-E
      mAb-induced granulocyte-mediated cytotoxicity against K562 targets, but bound
      F(ab')2 PNK-E mAb does not inhibit G7 mAb-induced granulocyte-mediated
      cytotoxicity, suggesting a physical association between the PNK-E and G7
      molecules on the surface of porcine granulocytes. PNK-E and G7 hybridoma cells
      are readily lysed by granulocyte effectors, further supporting that the PNK-E and
      G7 molecules are cytolytic trigger molecules on granulocytes. These data
      demonstrate that PNK-E and G7 mAb bind to distinct granulocyte lytic trigger
      molecules and induce potent granulocyte-mediated cytotoxicity against nucleated
      tumor targets through a mechanism of redirected cytotoxicity.

PMID- 8258716
TI  - Human granzyme B degrades aggrecan proteoglycan in matrix synthesized by
      chondrocytes.
AB  - Cartilage degradation, a hallmark of rheumatoid arthritis, is attributed to
      serine and metalloproteases secreted by neutrophils, synovial lining cells,
      macrophages, and chondrocytes. A large proportion of synovial fluid lymphocytes
      contains the granule-associated serine proteases granzymes A and B. We report
      that lysates of IL-2-stimulated lymphocytes contain an enzymatic activity
      (ECMase; cartilage extracellular matrix 35S release assay; extracellular matrix
      degrading activity) that solubilizes matrix synthesized by chondrocyte
      monolayers. ECMase activity is inactivated by the serine protease inhibitor
      diisopropylfluorophosphate, is stored in dense granules and cleaves aggrecan
      proteoglycans but not free glycosaminoglycans, hyaluronic acid, or type II
      collagen. ECMase is mediated by a cationic protein with biochemical properties
      identical to granzyme B, inasmuch as it preferentially hydrolyzes the substrate
      Boc-Ala-Ala-Asp-SBzl, immunochemically cross-reacts with an antibody that binds
      to a conserved amino-terminal region of lymphoid-myeloid serine proteases, and
      has amino-terminal sequence identity with human Q31 granzyme B. Using an agarose
      gel electrophoresis technique to assess cleavage of the rat sarcoma aggrecan, the
      catalytic efficiency of granzyme B for the digestion of aggrecan (catalytic
      efficiency = 1.7 x 10(7) M-1 s-1) was 425-fold faster than the catalytic
      efficiency reported for human stromelysin-1 at pH 7.5 (catalytic efficiency 4000
      M-1 s-1) and 3200-fold faster than granzyme A. Based on these observations, we
      propose that granzyme B, secreted from cytotoxic lymphocytes within the
      rheumatoid joint, may contribute to cartilage loss by degrading resident
      aggrecan.

PMID- 8258717
TI  - Evidence for a specific IgA receptor in rat and human mesangial cells.
AB  - Previous works have demonstrated that mesangial cells (MC) possess Fc receptors
      for IgG. We have investigated whether serum IgA could bind to MC in culture
      through a specific receptor. The binding of 125I-IgA (4 degrees C, 60 min) to MC
      was dose dependent and saturable, and the Scatchard analysis revealed a
      population of 1 x 10(5) binding sites per cell with a Ka of 7.8 x 10(8) M-1. This
      receptor was specific for IgA because unlabeled IgA and its Fc fragment were able
      to inhibit the binding, whereas IgG, IgM, and the IgA F(ab) fragment were not.
      Parallel experiments showed that human IgA bound in a similar manner both in a
      homologous system (human MC) and in heterologous systems (rat MC and peritoneal
      macrophages). In saturation studies using neuraminidase-desialylated IgA
      (desIgA), which has more carbohydrate residues exposed to binding, similar
      results to those of untreated IgA were obtained. Incubation with several
      carbohydrates decreased the IgA and desIgA binding to MC, obtaining maximal
      inhibition with simultaneous addition of galactose and N-acetyl-galactosamine.
      The possible IgA receptor (IgA-R) was purified from MC by affinity chromatography
      on an IgA-Sepharose column and appeared on SDS-PAGE gels as a 60-kDa band. The
      expression of IgA-R molecules on MC was enhanced by the presence of IgA in the
      culture medium. Finally, a band comparable with that of U937 cells was shown by
      Northern blot assay hybridizing mRNA from rat and human MC with a cDNA probe for
      the Fc alpha R. Taken together, these results strongly suggest the existence of a
      60-kDa protein on the surface of MC that is able to bind IgA with high affinity.

PMID- 8258718
TI  - Nitric oxide signaling: a possible role for G proteins.
AB  - We have previously reported various inductive effects of nitric oxide on human
      PBMC. We describe a novel and potentially important mechanism of nitric oxide
      signaling-through direct activation of guanine nucleotide-binding proteins (G
      proteins). We have found that nitric oxide treatment of membranes isolated from
      fresh human PBMC enhances the ability of these membranes to hydrolyze [gamma
      32P]GTP and bind [gamma-35S]GTP. In addition, treatment of whole cells with
      nitric oxide yielded membranes with enhanced GTPase activity. Furthermore, the
      GTPase activity of pure, recombinant Gs alpha, Gi alpha 1, and p21ras was greatly
      enhanced by nitric oxide. In support of the existence of this pathway in whole
      cells, we found that the G protein inhibitor, GDP-beta-S, blocked NF-kappa B
      translocation induced by nitric oxide or LPS in permeabilized cells. In addition,
      nitric oxide greatly reduced the pertussis toxin-mediated ADP-ribosylation of 45-
      and 41-kDa proteins in membranes of these cells. Because G proteins play a
      central role in many diverse signaling systems, activation by an endogenous and
      inducible oxidant may represent a novel signaling pathway.

PMID- 8258719
TI  - Association of all three types of Fc gamma R (CD64, CD32, and CD16) with a gamma
      chain homodimer in cultured human monocytes.
AB  - Receptors for the Fc region of IgG (Fc gamma R) on mononuclear phagocytes have
      been shown to play an important role in the removal of IgG-opsonized particles
      from the circulation. We found that all three types of Fc gamma R (CD64, CD32,
      and CD16) in cultured human monocytes are associated with the gamma-chain
      homodimer that is also present in the high affinity receptor for IgE.
      Immunoprecipitates of each of these Fc gamma R, prepared from 1% digitonin
      lysates of cultured human monocytes, incorporated phosphate into a gamma-chain
      homodimer when incubated with [gamma-32P]ATP. Fc gamma RII immunoprecipitates
      also incorporated phosphate into Fc gamma RII itself. When human alveolar
      macrophages were used, similar results were obtained. Although to a minor extent,
      each anti-Fc gamma R immunoprecipitate from freshly purified monocytes also
      coprecipitated gamma-chains. These Fc gamma R and gamma-chains did not constitute
      one large complex, because anti-Fc gamma RI or anti-Fc gamma RIII
      immunoprecipitates did not coprecipitate Fc gamma RII. In addition, F (ab')2
      fragments of anti-Fc gamma R mAb bound to intact cells were recovered in the anti
      gamma-chain immunoprecipitates but not in immunoprecipitates made with anti-Fc
      gamma RIII or anti-Fc gamma RII mAb. When recovery of radioactivity in anti-gamma
      chain immunoprecipitates was compared with that in anti-mouse-Ig
      immunoprecipitates, approximately 25% of the Fc gamma RI and 20% of the Fc gamma
      RII expressed at the cell surface were associated with gamma-chains. The gamma
      chains may play an important role in signal transduction via Fc gamma R in human
      macrophages.

PMID- 8258720
TI  - Comparison of the allergenicity of ovalbumin and ovalbumin peptide 323-339.
      Differential expansion of V beta-expressing T cell populations.
AB  - We analyzed the effects of sensitization of BALB/c mice to the OVA peptide amino
      acids 323-339, on the development of an IgE response, immediate cutaneous
      hypersensitivity and airways responsiveness (AR). Daily aerosolization of OVA 323
      339 for 20 min over a period of 10 days was as effective in the stimulation of a
      serum anti-OVA IgE antibody response as sensitization to native OVA by the same
      route. After sensitization to native OVA, the majority of the IgE anti-OVA
      response was directed against peptide 323-339. The antibody responses were
      paralleled by skin test responses in sensitized mice: 73% of OVA-sensitized mice
      developed immediate type reactions when tested with native OVA and 82% of the
      mice had positive immediate skin test responses to intradermal injection of
      peptide 323-339. After sensitization to the peptide, 69% of the mice had positive
      responses to native OVA and 77% responded to peptide 323-339. Aerosolization of
      OVA as well as OVA 323-339 led to a comparable increase in airway responsiveness
      as measured by electrical field stimulation of tracheal smooth muscle
      preparations. To characterize T cell subpopulations that were stimulated after
      allergen sensitization, the distribution of specific V beta-expressing T cells
      was analyzed in local draining lymph nodes of the airways and the lungs. These
      lymph nodes were found to be enlarged after both OVA and OVA peptide
      sensitization. Sensitization to native OVA resulted in an increased percentage of
      V beta 8.1 and V beta 8.2 T cells whereas selective stimulation of V beta 8.1 T
      cells was found after peptide sensitization. These data indicate that OVA peptide
      323-339 represents a T and B cell epitope of OVA, which is important in the
      generation and development of immediate hypersensitivity responses in BALB/c
      mice.

PMID- 8258721
TI  - Recruitment of inflammatory cells to the pleural space. Chemotactic cytokines, IL
      8, and monocyte chemotactic peptide-1 in human pleural fluids.
AB  - Pleural effusions secondary to various diseases are associated with the presence
      of different inflammatory cells. The role of selective chemotactic cytokines in
      the recruitment of phagocytes to the pleural space is unclear. IL-8 and monocyte
      chemotactic peptide-1 (MCP-1) are recently described cytokines that are
      chemotactic for neutrophils and monocytes, respectively. We prospectively studied
      63 patients, using strictly defined criteria for their selection. IL-8
      concentrations were elevated in both empyema fluid (9.15 +/- 0.89 ng/ml) and
      parapneumonic effusions (4.7 +/- 0.697 ng/ml) when compared with pleural
      effusions secondary to other diseases. IL-8 levels were higher in empyema fluid
      than in parapneumonic effusions (p = 0.01). There was a significant correlation
      between IL-8 levels and the total numbers of neutrophils in empyema fluids (r =
      0.80). Chemotactic activity for neutrophils was elevated in empyema fluid and the
      addition of IL-8 neutralizing serum decreased bioactivity by 32.22%. Malignant
      pleural effusions had the highest levels of MCP-1 (12.0 +/- 3.7 ng/ml) when
      compared with others. Cytology-positive pleural fluids (n = 10) had a higher
      level of MCP-1 than cytology-negative effusions (p = < 0.05). Malignant pleural
      fluid MCP-1 levels correlated (r = 0.70) with the absolute number of monocytes in
      the pleural fluid. Neutralization of monocyte chemotactic activity of malignant
      pleural fluid by specific neutralizing serum caused a 70.3% inhibition of
      bioactivity. Immunohistochemical staining of malignant pleural fluid localized
      antigenic MCP-1 to malignant cells. We conclude that both IL-8 and MCP-1 play
      major but not exclusive roles in the recruitment of neutrophils and monocytes
      from the vascular compartment to the pleural space.

PMID- 8258722
TI  - Use of C6-deficient rats to evaluate the mechanism of hyperacute rejection of
      discordant cardiac xenografts.
AB  - C plays a critical role in the hyperacute rejection (HAR) of discordant
      xenografts (Xg), but the relative contribution of early vs late C components is
      unknown. In this study, genetic differences in C6 activity were correlated with
      HAR of guinea pig cardiac Xg by the rat. Seven rat strains were tested for C
      activity. Six strains (PVG.R1 (R1), PVG.1A (1A), DA, W/F, F344, LEW) had readily
      detectable C activity in the total and alternative pathways. Some PVG rats also
      had adequate C activity [PVG (C+)] but others [PVG (C-)] had a profound C6
      deficiency. All rats with adequate C activity (n = 35) rejected cardiac Xg
      between 15 and 80 min. PVG (C+) (n = 6) rats also rejected cardiac Xg
      hyperacutely (26 +/- 12 min), whereas PVG (C-) (n = 16) rats, which had high
      preformed IgM natural antibody titers, rejected cardiac Xg in 1 to 2 days (2678
      +/- 542 min). Transfer of serum from R1 rats to PVG (C-) recipients with
      vigorously beating Xg caused HAR of cardiac Xg within 116 +/- 75 min. Transfer of
      fresh PVG (C-) serum or heat-inactivated R1 serum did not induce HAR. HAR was
      characterized by intravascular platelet aggregation and interstitial hemorrhage,
      whereas Xg transplanted to PVG (C-) recipients had patent vessels at 30 min but
      were heavily infiltrated by granulocytes and monocytes at 2 days. These findings
      indicate that a deficiency in C6 prevents HAR but allows an accelerated acute
      rejection that may be mediated by the generation of vasoactive and chemotactic
      C3a and C5a.

PMID- 8258723
TI  - Induction of lupus-associated autoantibodies by immunization with native and
      recombinant Ig polypeptides expressing a cross-reactive idiotype 4B4.
AB  - A human mAb designated 4B4 with anti-Sm activity was derived from a patient with
      systemic lupus erythematosus. This antibody expressed a lupus-associated cross
      reactive Id, partially related to the monoclonal murine anti-Sm (Y2) from MRL/lpr
      mice. Studies were performed to investigate the ability of 4B4 to induce lupus in
      nonautoimmune-prone mice. BALB/c mice immunized with 4B4 produced antibodies to
      dsDNA, ssDNA, Sm ribonucleoprotein, and mouse Fc fragment. There was no antibody
      activity against SSA/Ro, SSB/La, and hen egg lysozyme. Ag inhibition studies show
      that the autoantibodies were not polyreactive. Mice were also immunized with r4B4
      polypeptides representing the H/L heterodimer, H chain and L chain.
      Autoantibodies were induced in mice immunized against the H/L and H polypeptides.
      No autoantibodies were induced in mice immunized with recombinant L chain.
      Furthermore, from 20 to 68% of antibody activity to Sm or dsDNA could be
      inhibited with anti-Id antiserum (either anti-4B4 or Y2). The autoantibody was
      initially IgM and then underwent an isotype switch to IgG. These results show
      that lupus-associated autoantibodies can be induced by immunization with 4B4 and
      that the 4B4 VH region is important in this induction process. The finding of
      murine IgG autoantibody expressing a cross-reactive Id similar to the immunizing
      4B4 suggests a role for anti-idiotypic Th cells in this autoimmune response.

PMID- 8258725
TI  - A novel, antigen-presenting function of melanocytes and its possible relationship
      to hypopigmentary disorders.
AB  - It is now well established that cultured human melanocytes are capable of
      expressing immunologically important cell surface molecules and that they can
      produce cytokines. Not all cells with the ability to express MHC class II
      molecules are capable of effective Ag presentation. However, the dendritic nature
      of melanocytes, their strategic position within the skin, and their phagocytic
      capacity seem to suggest a role for these cells in processing and presenting Ag.
      This study demonstrates that cultured normal human skin melanocytes can present
      peptide Ag, and process and present the mycobacterial HSP65 kDa protein and whole
      Mycobacterium leprae sonicate to CD4+ cytotoxic proliferative T cell clones in an
      Ag-specific and HLA-class II-restricted manner. T cell stimulation was dependent
      on costimulatory signals, i.e., LFA-3/CD2 and LFA-1/ICAM-1. Besides eliciting a T
      cell proliferative response, our studies further demonstrate that melanocytes can
      function as target cells for T cell-mediated cytotoxicity. The described Ag
      processing and -presenting functions of melanocytes, taken together with in vivo
      behavior of melanocytes in hypopigmentation, provide new clues for the
      etiopathogenesis of melanin pigmentary disorders.

PMID- 8258724
TI  - Regulation of anti-Sm autoantibodies by the immunoglobulin heavy chain locus.
AB  - Anti-Sm antibodies are specific markers for systemic lupus erythematosus in MRL
      mice and in humans. The prevalence of anti-Sm positivity in inbred MRL/Mp
      lpr/lpr(MRL/lpr) mice is consistently about 25% at 5 mo of age, when the disease
      is at its peak. The control of the development of anti-Sm in individual MRL/lpr
      mice has been shown to be the result of stochastic factors, and previous research
      has indicated that the immunoglobulin heavy chain (IgH) b allotype may be more
      amenable to the production of anti-Sm. We have now further investigated the
      influence of the IgH genetic locus on the production of anti-Sm and other
      autoantibodies in an allotype congenic MRL strain, the MRL/Mp-Ipr/Ipr-IgHb
      (MRL/lpr-IgHb). Strikingly, 78% of MRL/lpr-IgHb mice produced anti-Sm, compared
      with 27% of contemporaneous MRL/lpr (IgHj) mice. Of those mice that were positive
      for anti-Sm, the MRL/lpr-IgHb strain produced significantly higher levels of anti
      Sm than did the anti-Sm positive MRL/lpr mice. No differences were observed
      between the conventional MRL/lpr and the MRL/lpr-IgHb levels of antichromatin,
      anti-ssDNA, antiribosomal P, or anti-Su. In addition, kidney function, which was
      assessed by measuring serum urea nitrogen levels, was similar in the two strains.
      These results support the notion that the control of anti-Sm production in
      MRL/lpr mice operates through the IgH locus.

PMID- 8258726
TI  - Engraftment of human synovium into severe combined immune deficient mice.
      Migration of human peripheral blood T cells to engrafted human synovium and to
      mouse lymph nodes.
AB  - To determine the feasibility of using the C.B-17 scid/scid (severe combined
      immune deficient, SCID) mouse as a recipient of human synovial xenografts, we
      have engrafted human synovium under the renal capsule of SCID mice, and
      determined synovial graft survival and histologic characteristics 4 to 7 wk after
      tissue implantation. Both normal and inflammatory synovial tissue grew well in
      SCID mice and maintained histologic and phenotypic components of the fresh
      synovial tissue before implantation. However, the number of T cells in synovial
      grafts decreased after implantation. To determine whether leukocytes could
      migrate to human synovial xenografts, either allogenic or autologous PBMC were
      injected in the peritoneum of SCID mice bearing synovial xenografts. We found
      that 7 days after i.p. injection of autologous or allogeneic PBMC, injected T
      cells had selectively migrated to human synovial grafts and to SCID mouse lymph
      nodes. Our data demonstrate that normal and inflammatory human synovial tissues
      will grow in SCID mice and serve as recipients for autologous and allogenic
      peripheral blood human T cells injected i.p. into engrafted mice.

PMID- 8258727
TI  - [Inhibitory effects of oral administration of ginsenoside Rh2 on tumor growth in
      nude mice bearing serous cyst adenocarcinoma of the human ovary].
AB  - We examined the inhibitory effect of the oral administration of ginsenoside Rh2
      (Rh2) on tumor growth in nude mice bearing human ovarian cancer cells (HRA). In
      the first experiment, it was revealed that daily administration of 30 microM Rh2
      significantly inhibited tumor growth. In the second experiment, therefore,
      various concentration of Rh2 (1, 15, 30, 60, 120 microM) were administered every
      day for 91 days, beginning the day after tumor inoculation. Treatment with Rh2
      resulted in a remarkable retardation of the HRA cell tumor growth. In particular,
      tumor growth in mice treated with 15, 30 and 120 microM Rh2 was significantly
      inhibited, compared to that in CDDP treated mice as well as in untreated mice.
      Consequently, 50% survival in nude mice treated with 15, 30 and 120 microM Rh2
      was significantly prolonged, compared to that not only in untreated mice but also
      in CDDP treated mice. No side effect was observed in any mice treated with Rh2.
      Red ginseng containing Rh2 has been used exclusively, orally administered. In the
      present study, we considered that oral administration of Rh2, which is a
      component of red ginseng, has strong inhibitory effects on human ovarian cancer
      cell growth in nude mice.

PMID- 8258728
TI  - [Studies on the point mutation of ras oncogene in ovarian tumor].
AB  - Thirty-five patients with ovarian tumors operated on between December, 1989 and
      June, 1991 were studied to detect K-ras codon 12 point mutation (PM). (1) Five of
      35 ovarian tumors (14.3%) disclosed K-ras PM at codon 12 and all the PM cases
      were in transition from GGT to GAT. On the other hand only one case (5.3%) with K
      ras oncogene amplification was found and no C-myc or erbB-2 amplification was
      detected. (2) The incidence of PM according to clinical stages was seen in 3 of
      11 stage I cases (27.3%), in 1 of 3 stage II cases (33.3%), in 1 of 14 stage III
      cases (7.1%) and in neither of 2 stage IV cases. PM was therefore seen in
      relatively early stages. (3) The occurrence of PM according to the histologic
      type was found in 3 of 16 serous tumors (18.8%), in 2 of 5 mucinous tumors
      (40.0%) and in none of 7 clear cell carcinomas or 2 endometrioid carcinomas. (4)
      Concerning the relation of PM to the involvement of serosal surface of ovarian
      tumors and to the ascitic cytology, no particular correlation was observed in our
      study. (5) Regarding the cytologic findings in imprint smears of the tumors in
      reference to PM, such as nuclear size, shape, N/C ratio, chromatin pattern,
      nucleolar size and number, the cases with PM tended to have more multiple
      nucleoli than PM negative cases. No other findings seemed to indicate the
      clinical progress of cancer. In conclusion, our study indicated that PM in
      ovarian cancers was a relatively early event in carcinogenesis.

PMID- 8258729
TI  - [A study of first and second line chemotherapies in gestational choriocarcinoma].
AB  - Twenty-eight patients with choriocarcinoma have received the three kinds of
      combination chemotherapy since 1983 at our department, i.e., MOA consisting of
      moderate dose methotrexate (MTX), actinomycin-D (Act-D) and vincristine, MEA
      (moderate dose MTX, Act-D and etoposide) and FA (high dose 5-Fluorouracil and Act
      D). The clinical and laboratory data obtained in the 28 patients were summarized
      as follows; 1. The MOA regimen was administered to 4 patients primarily and to 2
      secondarily. All of the 6 patients attained remission, but finally two (33.3%)
      developed relapse. 2. The MEA regimen was administered to 12 patients primarily
      and to 12 secondarily. Of the 24 patients, five (20.8%) were found to be
      resistant to the MEA regimen. Nineteen patients (79.2%) attained remission, but 2
      (10.5%) developed recurrence. 3. The FA regimen was attempted in one patient
      primarily and in 6 secondarily. Although one patient died, the remaining 6
      achieved remission and one relapse has been observed in the 6 cases. 4. By
      applying the above mentioned 3 combination chemotherapy regimens, the overall
      survival rate was pushed up from 64% to 90% in choriocarcinoma patients. 5. Three
      patients finally died of the disease but not from the side effects of the
      combination chemotherapies. The major adverse effects were alopecia, nausea,
      vomiting and myelosuppression. In particular, serious myelosuppression was caused
      by the MEA or FA regimen in 5-7% of all chemotherapy courses.

PMID- 8258730
TI  - [Laparoscopic resection of ovarian cysts: precautions and improvements in the
      procedure and application of the mini-laparotomy].
AB  - We previously devised and reported a laparoscopic resection of benign ovarian
      cysts. In the present paper, we report precautions and improvements in the
      procedure and the application of the mini-laparotomy. 1. The subjects consisted
      of a total of 41 cases with preoperatively diagnosed cysts. These were 17 cases
      with simple cysts, 15 cases with dermoid cysts, and nine cases with chocolate
      cysts. The present surgical procedure was performed on 34 (83%) cases. 2. One
      case, preoperatively diagnosed as a chocolate cyst, was diagnosed as an
      endometrioid adenocarcinoma. 3. Laparotomy was required in 7 cases; in four as a
      result of hard adhesions, in one because it was impossible to withdraw fluid, in
      one due to a damaged urinary bladder and in one due to endometrioid
      adenocarcinoma. 4. It became essential to classify the ovarian cysts into three
      groups according to size. 5. Mini-laparotomy was performed for two giant ovarian
      cysts and five ovarian cysts in pregnant women. In this procedure the goal is
      minimal, simple, safe and reliable surgery with results equal to those of
      standard laparotomy.

PMID- 8258731
TI  - [Effect of epidermal growth factor (EGF) on mouse sperm capacitation].
AB  - The effect of epidermal growth factor (EGF) on the kinetics of mouse sperm
      capacitation was examined. The chlortetracycline (CTC) fluorescence assay was
      used to monitor capacitated sperm, featuring a B pattern. One hundred ng/ml EGF
      significantly stimulated capacitation at 15 minutes after the addition. However,
      0.1 pg/ml EGF did not stimulate capacitation. EGF affected neither the motility
      nor the appearance of the S or AR pattern. The EGF-induced stimulation of
      capacitation was attenuated by 20 micrograms/ml genistein, an inhibitor of
      protein tyrosine kinase, or by 100 ng/ml thapsigargin, a non-phorbol tumor
      promoter, which inhibits EGF action by enhancing phosphorylation of the threonine
      669 residue of the EGF-receptor. However, 3 ng/ml 12-O-tetradecanoly phorbol 13
      acetate (TPA), a stimulator of protein kinase C, did not attenuate the appearance
      of the B pattern enhanced by 100 ng/ml EGF. These data suggest that EGF
      stimulates mouse sperm capacitation by activating the tyrosine kinase of the EGF
      receptor which is regulated by multisite phosphorylation.

PMID- 8258732
TI  - [The limitation of the anti-Chlamydia antibody test with special reference to the
      antigen positive non-pregnant women].

PMID- 8258733
TI  - [Continuous intravenous infusion of ritodrine using a portable balloon pump].

PMID- 8258734
TI  - [A case of hCG-producing cervical carcinoma of uterus].

PMID- 8258735
TI  - [A case of uterine rupture with the use of gemeprost suppositories in second
      trimester pregnancy termination].

PMID- 8258736
TI  - [A case of pseudomyxoma peritonei successfully treated with intra-peritoneal
      hyperthermia].

PMID- 8258737
TI  - [A report of two cases of the preeclampsia with proteinuria effectively treated
      with the haptoglobin].

PMID- 8258738
TI  - [Prenatal diagnosis of chronic granulomatous disease by percutaneous umbilical
      blood sampling].

PMID- 8258739
TI  - Review of platinum anticancer compounds.

PMID- 8258740
TI  - Progression of chronic renal disease and diabetic nephropathy: a review of
      clinical studies and current therapy.
AB  - Animal studies on the progression of chronic renal disease have limited
      applicability to humans. However, human kidneys also progressively deteriorate
      once they have suffered a certain degree of initial damage. Various therapeutic
      approaches to slowdown the progression of chronic renal disease [low-protein
      diets, angiotensin converting enzyme (ACE) inhibitors, etc.] seem promising.
      Large-scale, ongoing clinical studies may offer definitive answers to their place
      in the management of progressive renal disease. Diabetic nephropathy, the most
      common cause of end-stage renal failure, follows a distinct course in insulin
      dependent diabetes mellitus DM (IDDM); this is less well defined in non-insulin
      dependent DM (NIDDM). Micro-albuminuria is an important hallmark of early
      diabetic kidney disease, when it may still be amenable to therapeutic
      interventions. Strict glycemic control, and ACE inhibitors may be beneficial in
      early stages of diabetic nephropathy. Less is known on use of calcium-channel
      blockers and low-protein diets in diabetic nephropathy. There is also a paucity
      of information on management of diabetic nephropathy in type II DM.

PMID- 8258741
TI  - Classifying cytostatics on the basis of their angiocidal and angiostatic effects.
AB  - This study describes the effects of ten clinically used cytostatics [bleomycin
      (BLM), cytarabine (Ara-C), cyclophosphamide (CTX), doxorubicin (DOX), etoposide
      (VP-16), 5-fluorouracil (5-FU), methotrexate (MTX), mitoxantrone (MXN),
      vincristine (VCR), and vinblastine (VLB)] on the chorioallantoic membrane vessels
      -especially on vessel counts--and on the weight of the chicken embryo. A
      significant reduction of vessel counts (VC) due both to angiocidal and an
      angiostatic action, was induced by DOX, MXN, VP-16, VCR, and VLB. 5-FU and BLM
      induced only a (weak) angiostatic effect. MTX, Ara-C, and CTX were neither
      angiocidal nor angiostatic. The classification of cytostatics presented here
      might have implications for their use in the clinical treatment of malignant
      tumors.

PMID- 8258742
TI  - Elemental analysis of hair among children living in Bangkok, Negros Island and
      Takarazuka. A comparative study in three countries.
AB  - Twelve elements in the hair of children living in Bangkok (Thailand) were
      compared with those of children living in Negros Island (Philippines) and
      Takarazuka (Japan). With the exception of lower Se and F values, the contents of
      Ca, Mg, Na, K, Fe and Al in the hair of children in Bangkok were higher than
      those in Japanese children. A high coefficient of correlation was obtained
      between Cu and Fe, Cu and Mn, Se and Fe, Se and Cu, Se and Mn in the children of
      Bangkok. These findings were not found in other groups.

PMID- 8258743
TI  - Biochemical changes after a 100 km hill walk.
AB  - Biochemical changes after a 100 km hill walk were studied in 16 subjects (nine
      male and seven female). Plasma concentrations of potassium, albumin and total
      protein were lower, and the concentrations of phosphate, urea, alanine
      transaminase (ALT) and bilirubin were higher after the walk than before.
      Activities of creatine kinase (CK), lactate dehydrogenase (LD) and their
      isoenzymes CKMB and LD1 increased several fold after the walk. Although CKMB
      increased, the relative amount of CKMB was less than that seen in myocardial
      infarction. We conclude that after a 100 km hill walk there is evidence of plasma
      volume expansion, muscle damage, and increased protein breakdown.

PMID- 8258744
TI  - Masked atrial septal defect in constrictive pericarditis.
AB  - The combination of an atrial septal defect (ASD) and constrictive pericarditis
      (CP) is rare and difficult to diagnose, since the signs of ASD may be masked by
      those of CP. We report a patient in whom the diagnosis was made by color Doppler
      echocardiography and magnetic resonance imaging (MRI), and confirmed by cardiac
      catheterization. Open heart surgery was successfully performed to close the
      defect.

PMID- 8258745
TI  - IGFs: function and clinical importance.

PMID- 8258746
TI  - Growth hormone, insulin-like growth factor I, and bone: a clinical review.

PMID- 8258747
TI  - Therapeutic potential of rhIGF-I in diabetes and conditions of insulin
      resistance.

PMID- 8258748
TI  - Therapy with recombinant human insulin-like growth factor I in children with
      insensitivity to growth hormone and in catabolic conditions.

PMID- 8258749
TI  - Hyperandrogenicity in women--a prediabetic condition?

PMID- 8258750
TI  - The risk of hip fractures in patients with primary hyperparathyroidism: a
      population-based cohort study with a follow-up of 19 years.
AB  - OBJECTIVE: To evaluate primary hyperparathyroidism (HPT) as a risk factor for hip
      fractures. DESIGN: A population-based, record-linked, prospective study with a
      mean observation time of 17 years (women) and 16.5 years (men). SETTING: A cohort
      obtained from a register of hospital admissions in the Uppsala Health Care
      Region, Sweden, 1965-1983. PARTICIPANTS: All patients (1373 women and 551 men)
      who were admitted to hospital with the diagnosis of HPT during the period.
      Comparisons were made with the entire background population. MEASUREMENTS: Cohort
      subjects were followed with regard to a first instance of hip fracture prior to
      or after the diagnosis of HPT. The observed number of cases was compared with
      that expected on the basis of person-years of observation and incidence rates in
      the background population. Analyses were made for cervical and trochanteric
      fractures, and for patients operated and not operated for HPT. MAIN RESULTS: (i)
      Women. During 23,341 person-years of observation, 67 cases of first hip fractures
      occurred, yielding a relative risk (RR) of 0.93 (95% confidence interval [CI]
      0.72-1.19). The RR for cervical fractures was 0.77 (CI 0.54-1.06), and for
      trochanteric fractures 1.33 (CI 0.88-1.93). Operation for HPT did not influence
      the risk of hip fracture. (ii) Men. The total person-years was 9091. Eleven
      fractures were observed--compared with the expected 7.90 (RR 1.39; CI 0.69-2.50).
      Men operated for HPT had an increased risk for cervical hip fractures (RR 2.73;
      CI 1.18-5.39). Owing to the few fractures in this group (n = 8) the relevance of
      this is uncertain. CONCLUSIONS: This study indicates that HPT is not a risk
      factor for hip fractures in women.

PMID- 8258751
TI  - Response of hypertension to conventional antihypertensive treatment and/or
      steroidogenesis inhibitors in Cushing's syndrome.
AB  - OBJECTIVES: To evaluate the effect of conventional antihypertensive drugs and/or
      inhibitors of steroid production in the management of hypertension in Cushing's
      syndrome. DESIGN: A retrospective open clinical study with pre- and post
      treatment assessment. SETTING: A university hospital, where patients were
      initially admitted and then followed-up in an ambulatory clinic over a period of
      6 years. SUBJECTS: Forty consecutive hypertensive patients with Cushing's
      syndrome. INTERVENTIONS: Patients were divided into two groups according to the
      different management of hypertension. The first group (group 1) of 28 patients
      included those treated with antihypertensive drugs at full dose (diuretics,
      calcium antagonists, angiotensin converting enzyme [ACE] inhibitors, as single
      agents or in combination). The second group (group 2) of 12 patients received
      ketoconazole alone. MAIN OUTCOME MEASURES: Blood pressure variations compared to
      pre-treatment levels. RESULTS: Blood pressure normalization was obtained in four
      of the 28 patients of group 1. In 12 of the remaining patients, ketoconazole, an
      inhibitor of steroid production, was subsequently added and this normalized blood
      pressure in all but the one in whom cortisol was not decreased. In the 12
      patients of group 2, ketoconazole alone lowered blood pressure within normal
      limits in all but one who had long-standing hypertension. CONCLUSIONS: In
      hypertensive patients with Cushing's syndrome, conventional antihypertensive
      therapy is mostly ineffective. Blood pressure response is satisfactory only after
      the restoration of normal cortisol levels, indicating the need for a specific
      treatment for hypertension in this disorder.

PMID- 8258752
TI  - Serum cholesterol concentration before and after streptokinase in acute
      myocardial infarction.
AB  - OBJECTIVE: To determine if serum cholesterol concentration should be measured
      before or after streptokinase therapy within the first 24 h of myocardial
      infarction. DESIGN: Prospective study of patients receiving streptokinase therapy
      for acute myocardial infarction (AMI). SETTING: Coronary care unit of a district
      general hospital. SUBJECTS: Thirty-one patients (26 men aged 38-74 years, mean 60
      years) admitted with a definite diagnosis of myocardial infarction. INTERVENTION:
      Streptokinase therapy given intravenously at a mean of 5 h (range 1.5-15 h) after
      the onset of chest pain. MAIN OUTCOME MEASURES: Serum cholesterol concentration
      just prior to, and 11.5 h (range 4-20.5 h) after streptokinase administration.
      RESULTS: There was a significant mean fall of 0.4 mmol l-1 (P = 0.002, 95% CI =
      0.2-0.6) in serum cholesterol concentration from a pre-streptokinase
      concentration of 7.0 (range 5.3-9.9) to a post-streptokinase concentration of 6.6
      (range 4.9-9.9). In the patients who showed a fall in cholesterol concentration,
      the magnitude of fall correlated with the baseline cholesterol concentration (r =
      0.66, P < 0.01) but not with peak cardiac enzyme activities (r = 0.05, P > 0.2
      for aspartate aminotransferase; r = 0.10, P > 0.2 for lactate dehydrogenase),
      time from onset of chest pain to post-streptokinase measurement (r = 0.27, P >
      0.2) or time from streptokinase administration to post-streptokinase measurement
      (r = 0.01, P > 0.2). CONCLUSION: Serum cholesterol concentration may be
      underestimated when measured after streptokinase therapy, particularly when the
      true basal value is high. Further management of this risk factor may be based
      more accurately on its measurement before than after streptokinase therapy within
      the first 24 h of AMI.

PMID- 8258753
TI  - High frequency of antibodies to Hantaan virus and hepatitis C virus in chronic
      haemodialysis patients. Coincidence or cross-reaction?
AB  - OBJECTIVES: To address the question of whether there is any coincidence or cross
      reaction between hepatitis C virus (HCV) and Hantaan virus (both RNA
      arboviruses), as well as to assess the frequency of antibodies to the above
      viruses amongst chronic haemodialysis patients in our region. DESIGN: Collection
      of serum samples from consecutive unselected chronic haemodialysis patients.
      SETTING: A tertiary referral center (University Hospital). SUBJECTS: One hundred
      and fourteen chronic haemodialysis patients were investigated for the presence of
      antibodies to HCV (anti-HCV) and Hantaan virus disease (anti-HVD). Eleven
      unselected non-haemodialysis patients with well-defined haemorrhagic fever with
      renal syndrome (HFRS) were also investigated for the anti-HCV antibodies
      comprising the disease control group. INTERVENTIONS: None. MAIN OUTCOME MEASURES:
      The utility of an anti-HVD positive test in chronic haemodialysis patients.
      RESULTS: Seventeen patients (14.9% 95% confidence interval [CI] 8.4-21.4%) were
      anti-HCV positive, whereas 15 (13.2%, 95% CI 6.9-19.3%) were anti-HVD positive.
      An anti-HCV positive test was confirmed by recombinant immunoblot assay (RIBA II)
      in 88.2%. The presence of anti-HCV antibodies was not associated with
      transfusions but with the longer duration of haemodialysis (62.8 +/- 29.8 vs.
      31.2 +/- 29.3 months, P < 0.001). Anti-HVD antibodies were not associated with
      transfusions or with the duration of haemodialysis. Three patients were positive
      for both anti-HCV and anti-HVD antibodies. None of the 11 patients with well
      defined HFRS had anti-HCV antibodies. CONCLUSIONS: Chronic haemodialysis patients
      are a high risk group for HCV infection in association with the duration of
      haemodialysis and, at least for our geographical area, these patients have to be
      examined for anti-HVD antibodies especially when a definite causative agent for
      chronic renal failure is not found. The HVD and HCV infection are not exceptional
      amongst haemodialysis patients in our region, whereas the possibility of a cross
      reaction between these two RNA arboviruses is rather excluded as there was no
      evidence of HCV infection amongst the patients with well-defined HFRS.

PMID- 8258754
TI  - Porphyric neuropathy: prevention of progression using haeme-arginate.
AB  - We report on a patient with acute intermittent porphyria (AIP) who, during
      treatment with hypertonic glucose, developed peripheral neuropathy. Once haeme
      arginate was started, the progression of the neuropathy was attenuated. This
      suggests that hypertonic glucose may be inadequate in preventing the development
      of neuropathy in a patient with porphyria. However, haeme-arginate, if started
      early, can attenuate the progression of porphyric neuropathy.

PMID- 8258755
TI  - Haemorrhagic bullae induced by oral anticoagulants.
AB  - A 77-year-old patient developed haemorrhagic bullae on her fingers 30 months
      after initiation of anti-coagulation treatment with warfarin sodium for chronic
      atrial fibrillation and mitral insufficiency. The bullae resolved 10 days after
      discontinuation of the medication. Two weeks after initiation of sintrom, (3
      alpha-(4-nitrophenyl)-beta-acetylethyl-4-hydroxy coumarin), the lesions recurred
      and resolved again upon cessation of the drug. This adverse skin reaction has not
      been hitherto reported.

PMID- 8258756
TI  - Unusual thrombotic-like retinopathy (Coats' disease) associated with congenital
      plasminogen deficiency type I.
AB  - A new kindred with heterozygous plasminogen deficiency type I is described. The
      proband, a 17-year-old male, showed a peculiar thrombotic-like retinal picture
      compatible with Coats' disease. Extensive coagulation studies revealed decreased
      levels of both plasminogen activity and antigen to about 50% of normal values.
      Five out of 13 family members from the paternal side showed the same fibrinolytic
      defect. In two cases, a history of recurrent phlebites of the lower limbs was
      present. One unaffected patient also had a superficial phlebites at a young age;
      her plasminogen levels were shown to be within normal limits, but a long-standing
      oestroprogestinic intake could have influenced and normalized the results. No
      other family member showed retinal abnormality. This is the first case of
      hypoplasminogenaemia associated with Coats' disease. A possible role of the
      fibrinolytic defect in the pathogenesis of this unusual retinopathy is suggested.
      Finally, the occurrence of thrombotic manifestations in other affected family
      members supports the opinion that plasminogen deficiency should be considered as
      a potential risk factor for thrombosis.

PMID- 8258757
TI  - Autoimmune polyglandular failure associated with malabsorption and gastric
      carcinoid tumour.
AB  - A 21-year-old female with autoimmune polyglandular failure (APG) manifested by
      insulin-dependent diabetes mellitus (IDDM), hypothyroidism and pernicious anaemia
      developed severe malabsorption due to exocrine pancreatic insufficiency.
      Supplemental pancreatic enzymes resulted in marked improvement of steatorrhea.
      There was also an incidental finding of gastric carcinoid tumour. We identified
      only 13 other patients in our institution with either type 2 or 3 APG, one of
      which had significant steatorrhoea. Another patient with IDDM, hypothyroidism and
      pernicious anaemia had an asymptomatic gastric carcinoid tumour. The possible
      mechanisms for malabsorption in APG are discussed.

PMID- 8258758
TI  - Stigma or legitimation? A historical examination of the social potentials of
      addiction disease models.
AB  - This article presents a historical discussion of disease models of opiate
      addiction in the United States in the twentieth century. First, several
      approaches to defining disease are discussed. Then, the shifts in formulations of
      opiate addiction as a disease in the twentieth century in the U.S. are analysed
      in light of the preceding theoretical discussion. The period before 1920 is
      described as heterodox, as researchers attempted to develop scientific models of
      opiate addiction, while various medically legitimate and quasi-legitimate
      treatment approaches flourished in an unregulated marketplace. After 1920, a
      stigmatizing disease model of opiate addiction was based on a psychiatric
      formulation that linked chronic addiction with psychoneurotic deficits in certain
      individuals. After 1940, this model dominated medical and scientific thinking
      about opiate addiction for several decades. After 1970, enormous changes in the
      demographics of drug use forced changes to the prevailing model of addiction. A
      new focus on behavioral aspects of addiction allowed the creation of a
      nonstigmatizing Parsonian disease model.

PMID- 8258759
TI  - Entangled epidemics: cocaine use and HIV disease.
AB  - Over the past decade, two epidemics have had a severe impact on public health in
      this country. These health problems involve cocaine abuse and AIDS (or HIV
      disease). The processes of these two conditions are clearly not independent of
      each other and may be quite complex. Understanding of this relationship has been
      hampered by a myriad of social, biological and behavioral variables that are
      entangled with the basic cocaine-HIV association. This article presents a
      paradigm for discussion of the interaction between cocaine exposure and HIV
      disease based on three mechanisms: the relationship between cocaine exposure and
      increased opportunity for HIV exposure, the direct role that cocaine plays in
      altering susceptibility to HIV infection, and the influence that cocaine use has
      on the progression of HIV disease. The goal of this structured approach is to
      enhance conceptual understanding of the cocaine-HIV relationship while
      recognizing the complexity of the issue and the limitations of current research
      efforts. This model will serve as a framework for the discussion of implications
      for future research, clinical practice, and public policy.

PMID- 8258760
TI  - Sociodemographic and attitudinal correlates of alcohol and other drug use among
      children and adolescents: analysis of a large-scale attitude tracking study.
AB  - Data from the Partnership Attitude Tracking Study are analyzed to provide a
      greater understanding of the contributing factors to alcohol and other drug use
      among children and adolescents. The data were collected from children (ages 9 to
      12) and teenagers (ages 13 to 17) in central locations (usually shopping malls)
      located in 100 primary sampling units across the United States. The analysis,
      which primarily employed stepwise multiple regression for model estimation,
      reinforced the importance of friends use, perceived risk, and tobacco and alcohol
      use in predicting marijuana use. An exposure model, which included antidrug
      advertisements, was a particularly powerful model. Implications of the findings
      are discussed.

PMID- 8258761
TI  - Issues to consider when predicting retention in therapeutic communities.
AB  - Many studies have focused on retention in therapeutic communities (TCs) because
      research shows that retention is an important predictor of client outcomes from
      these programs. A comparison of the three largest studies found there was little
      overlap between predictors of retention in TCs. Treatment Outcome Prospective
      Study data were analyzed to assess whether these findings may have been due to
      differences in times when the data were collected, measures of length of stay,
      and domains of variables used to predict retention. While the results suggest
      that each of these factors contributed to some differences between predictors of
      retention, the predictors still were unable to explain more than a small amount
      of the variance in retention. Research indicates that other variables need to be
      taken into account if future studies are to be more successful in predicting
      retention in TCs.

PMID- 8258762
TI  - Decline in HIV-1 seroprevalence and low seroconversion rate among injecting drug
      users at a methadone maintenance program in New York City.
AB  - To monitor the trend of HIV-1 seroprevalence, 2,194 newly admitted injecting drug
      users (IDUs) in a methadone maintenance program in New York City were tested from
      June 1988 through June 1992. This was a blinded study and unlabeled blood
      specimens were collected during the required physical examination. There was a
      significant linear trend (p = .01) toward decline in HIV-1 seropositivity by year
      of admission as follows: 47.0% in 1988, 43.4% in 1989, 43.2% in 1990, 39.8% in
      1991, and 39.1% in 1992. From January 1988 through December 1992, admissions data
      that included the newly admitted IDUs showed a significant decrease (p < .0002)
      in self-reported current needle sharing from 11.3% to 5.4%. These two data
      sources suggest that a continued decline in HIV-1 seroprevalence among new
      admissions may be related to decreased needle sharing. A volunteer cohort of 235
      HIV-1 seronegative IDUs was also enrolled from April 1990 through June 1991 in a
      study of HIV-1 seroconversion. Follow-up data were available on 177 patients for
      up to 12 months. For a total observation time of 155 person-years, there were two
      conversions (1.3 conversions per 100 person-years). A continued decline in HIV-1
      seroprevalence among new admissions and a low HIV-1 seroconversion rate among
      existing patients have contributed to a lower overall HIV-1 prevalence in clinic
      patients of about 40%. This stands in contrast to 1985-86 estimates of HIV-1
      seroprevalence that plateaued at 60%.

PMID- 8258763
TI  - Haight-Ashbury free clinics' drug detoxification protocols--Part 2: Opioid
      blockade.

PMID- 8258764
TI  - Methadone doses and psychopathological symptoms during methadone maintenance.

PMID- 8258765
TI  - Koro in heroin withdrawal.

PMID- 8258766
TI  - Referendum deletes criminal sanctions for drug users in Italy.

PMID- 8258767
TI  - Tissue distribution of fentanyl and alfentanil in the rat cannot be described by
      a blood flow limited model.
AB  - Traditionally, physiological pharmacokinetic models assume that arterial blood
      flow to tissue is the rate-limiting step in the transfer of drug into tissue
      parenchyma. When this assumption is made the tissue can be described as a well
      stirred single compartment. This study presents the tissue washout concentration
      curves of the two opioid analgesics fentanyl and alfentanil after simultaneous 1
      min iv infusions in the rat and explores the feasibility of characterizing their
      tissue pharmacokinetics, modeling each of the 12 tissues separately, by means of
      either a one-compartment model or a unit disposition function. The tissue and
      blood concentrations of the two opioids were measured by gas-liquid
      chromatography. The well-stirred one-compartment tissue model could reasonably
      predict the concentration-time course of fentanyl in the heart, pancreas, testes,
      muscle, and fat, and of alfentanil in the brain and heart only. In most other
      tissues, the initial uptake of the opioids was considerably lower than predicted
      by this model. The unit disposition functions of the opioids in each tissue could
      be estimated by nonparametric numerical deconvolution, using the arterial
      concentration times tissue blood flow as the input and measured tissue
      concentrations as the response function. The observed zero-time intercepts of the
      unit disposition functions were below the theoretical value of one, and were
      invariably lower for alfentanil than for fentanyl. These findings can be
      explained by the existence of diffusion barriers within the tissues and they also
      indicate that alfentanil is less efficiently extracted by the tissue parenchyma
      than the more lipophilic compound fentanyl. The individual unit disposition
      functions obtained for fentanyl and alfentanil in 12 rat tissues provide a
      starting point for the development of models of intratissue kinetics of these
      opioids. These submodels can then be assembled into full physiological models of
      drug disposition.

PMID- 8258768
TI  - Nonlinear mixed effect modeling of the pharmacodynamics of natriuretic peptides
      in rats.
AB  - Natriuretic peptides have not only natriuretic/diuretic but also hypotensive
      activities, and the decreased renal perfusion caused by the excessive hypotension
      is known to attenuate the diuretic actions. The present study was designed to
      examine the relationship between the dosing (intravenous constant infusion) rates
      and the diuretic actions of alpha-rat atrial natriuretic peptide (alpha-rANP) and
      rat brain natriuretic peptide (rBNP) in rats, and population (nonlinear mixed
      effect model) analysis was applied to these complicated diuretic actions. The
      intrinsic diuretic activities of alpha-rANP and rBNP could be analyzed, and the
      effects of blood pressure, heart rate, and also inhibition of degradation enzyme
      on the diuresis of natriuretic peptides were estimated simultaneously. The
      population analysis was useful for analyzing such pharmacodynamic data for which
      the individual analysis could not be applied easily.

PMID- 8258769
TI  - Kinetic analysis of AUC-dependent saturable clearance of liposomes: mathematical
      description of AUC dependency.
AB  - The objective of this study was to examine the AUC dependency of saturable
      hepatic clearance (CLh) of liposomes and to postulate a mathematical model to
      describe the characteristics. The AUC dependency of saturable CLh was examined
      under intravenous rapid administration at various doses. The CLh increased with
      increasing blood concentration but decreased with the increase of AUC at each
      dose. In addition, the relationship between AUC and CLh was consistent with that
      observed in previously reported infusion studies. These experimental data confirm
      the AUC dependency of saturable CLh of liposomes. A mathematical model was
      developed for this AUC dependency. The decrease of CLh was described by the
      uptake amount (X) as follows: CLh = CLm(1-X/Xm), where CLm and Xm represent the
      maximum uptake clearance and the maximum uptake amount, respectively. The rate
      equation for uptake was analytically solved as CLh = X/AUC = Xm/AUC(1
      exp(CLm/XmAUC)). Uptake clearance can be described by CLm, Xm, and AUC, and so
      uptake clearance is constant if AUC is constant. These experimental analyses and
      theoretical considerations show the validity of the AUC-dependent saturable CLh
      of liposomes.

PMID- 8258770
TI  - A pharmacokinetic-pharmacodynamic model for quantal responses with thiopental.
AB  - The pharmacokinetic-pharmacodynamic model developed here characterizes the
      relationship between simulated plasma concentrations of thiopental and two
      dichotomous endpoints determined at induction of anesthesia: loss of voluntary
      motor power (clinical endpoint), and burst suppression of the
      electroencephalogram (EEG endpoint). The model incorporated data from two
      separate thiopental patient studies: a pharmacokinetic study with 21 males, and a
      pharmacodynamic study with 30 males. In the pharmacodynamic study, cumulative
      quantal dose-response curves for the clinical and EEG endpoints were developed
      from observations made during a constant-rate infusion of thiopental. Population
      mean parameters, derived from the bolus pharmacokinetic thiopental study, were
      used to simulate concentration-time data for the 150 mg.min-1 thiopental infusion
      rate used in the dose-response study. A single biophase model incorporating the
      two endpoints was generated, combining the pharmacokinetic and pharmacodynamic
      data from the two groups. Estimates of the mean effective thiopental
      concentrations affecting 50% of the population (EC50S) for the clinical and EEG
      endpoints were 11.3 and 33.9 micrograms.ml-1, respectively. The half-time for
      equilibration between arterial thiopental and the effect compartment was 2.6 min.
      These results are in reasonable agreement with previously described quantal
      concentration-response data, and with pharmacodynamic models developed for graded
      EEG responses. Simulation of bolus doses of thiopental with the new model
      provided ED50s for the clinical and EEG endpoints of 265 mg and 796 mg,
      respectively; the dose predicted to produce loss of voluntary motor power in 90%
      of an adult male population was 403 mg. A model combining population
      pharmacokinetics with cumulative dose-response relationships could prove useful
      in predicting dosage regimens for those drugs with responses that are
      categorical.

PMID- 8258771
TI  - Assessing drug exposure in rodent toxicity studies without satellite animals.
AB  - Five major objectives for pharmacokinetic investigations in support of toxicity
      studies are identified as follows: Assess whether animals exhibited measurable
      blood concentrations in a dose-dependent manner; estimate average area under the
      concentration-time curve (AUC) and maximal concentration (Cmax) for each
      treatment group; elucidate general patterns in the concentration-time (CxT)
      profile, and summarize relationships between CxT and treatment group; determine
      CxT dependence on day into study; and judge interanimal variability and identify
      any animals with unusual concentration response. Such objectives are generally
      addressed in rodent toxicity studies by including "satellite" animals in the
      study. Satellite animals are extra animals dosed as per protocol but not
      subjected to toxicological and pathological observations and tests. Instead, they
      are used exclusively for the evaluation of pharmacokinetic characteristics of the
      test compound. In this paper, methods are described for achieving the five listed
      pharmacokinetic objectives in rodent toxicity studies without the use of
      satellite animals. A rat toxicity study is presented as an example.

PMID- 8258772
TI  - Spinal morphine anesthesia and urinary retention.
AB  - Spinal anesthetic is a common form of surgical anesthetic used in foot and ankle
      surgery. Spinal morphine anesthetic is less common, but has the advantage of
      providing postoperative analgesia for 12 to 24 hr. A number of complications can
      occur with spinal anesthesia, including urinary retention that may be a source of
      severe and often prolonged discomfort and pain for the patient. Management of
      this problem may require repeated bladder catheterization, which may lead to
      urinary tract infections or impairment of urethrovesicular function. This study
      reviews the incidence of urinary retention in 80 patients (40 after general
      anesthesia and 40 after spinal anesthesia) who underwent foot and ankle surgery
      at Saint Joseph's Hospital, Philadelphia, PA. Twenty-five percent of the patients
      who had spinal anesthesia experienced urinary retention, while only 7 1/2% of the
      group who had general anesthesia had this complication. Predisposing factors,
      treatment regimen, and recommendations for the prevention and management of
      urinary retention are presented.

PMID- 8258773
TI  - Gait style as an etiology to chronic postural pain. Part II. Postural
      compensatory process.
AB  - The body is designed to pull the center of mass over a single pivotal site formed
      by dorsiflexion of the first metatarsophalangeal joint. If this response
      dorsiflexion motion is blocked by functional hallux limitus, then the kinetic
      energy, which is created for this motion, must somehow be dissipated. The process
      by which this dissipation occurs creates a specific pattern of compensations
      which, in the past, has been seen as primary motions unrelated to sagittal plane
      blockade. These compensatory motions are described along with a brief section
      concerning the methods of treatment.

PMID- 8258774
TI  - Correlation between limb length discrepancy and asymmetrical rearfoot position.
AB  - Ten subjects with a known limb length discrepancy were filmed with the two
      dimensional Motion Analysis Foot Trak System; eight were filmed running and
      walking and two were filmed walking only. A control group of ten subjects with no
      measured limb length discrepancy was filmed in the same manner (eight walking and
      running and two walking only). The calcaneus-to-vertical angle was recorded for
      the entire stance gait cycle (heel contact to toe-off). Analysis of the data
      between the short and long side showed a significant difference in calcaneal
      position between the two sides at midstance, with the longer side being more
      everted by 3 degrees or greater than the short side in most cases. There was no
      significant difference in the calcaneus-to-vertical angle at heel contact between
      the long and short side. There was no significant difference between the
      calcaneus-to-vertical angles of the right and left sides of the ten control
      subjects, either walking or running.

PMID- 8258775
TI  - Magnetic resonance imaging of giant cell tumor of bone.

PMID- 8258776
TI  - Actinomycosis. A rare pedal infection.

PMID- 8258777
TI  - Digital clubbing. A case study.
AB  - In this case, it is difficult to assess whether the severity of the clubbed
      digits is a result of a purely hereditary nature, liver pathology, chronic
      respiratory ailments, or a combination of the above. The abnormal liver function
      test may not be related to the digital clubbing. Instead, they may be the result
      of the alcohol abuse. The case does appear to be hereditary because his siblings
      and mother all have clubbed digits and there is a higher frequency in blacks. The
      authors believe that this case affords an opportunity to make the podiatrist
      aware of the possibilities that should be considered the differential diagnosis
      when examining a patient with clubbed digits. It is important to fully work up a
      patient with clubbed digits even if the presentation is that of hereditary
      clubbing. Severe clubbing may be the result of a mild hereditary form that was
      worsened by an underlying systemic condition, such as malignancy, toxicosis,
      endocrinopathy, and neuropathy.

PMID- 8258778
TI  - Bilateral syndactyly. A unique case with surgical correction.
AB  - Cases must be treated on an individual basis, appreciating the complexity of the
      syndactyly, considering the patient compliance, and understanding the goals of
      the surgical correction. Extensive discussion with the patient and parents must
      occur to clarify the goals of the surgery, the expectations, and possible
      complications. Careful preoperative planning and incision design is paramount in
      obtaining satisfactory results. Skin grafting may be required, either full
      thickness from a variety of donor sites or split-thickness grafting as in one
      case study reported. Adjunctively, manipulation and stretching of the web space
      for 2 to 3 months preoperatively may be helpful to achieve more laxity of the
      soft tissues. The choice of suture material is of particular concern when dealing
      with a small child. It is usually wise to use an absorbable suture material for
      skin closure in a small child to prevent undue emotional stress to the child or
      even further anesthesia upon suture removal. Vascular compromise caused by soft
      tissue tension in not an infrequent occurrence. As with any surgery that
      addresses largely cosmetic deformities, there is no substitute for exact prior
      planning, meticulous technique, and surgeon experience to optimize results.

PMID- 8258779
TI  - Treatment of a gunshot nonunion to the second metatarsal by compression
      osteosynthesis.

PMID- 8258780
TI  - Tophaceous gout. An unusual presentation.

PMID- 8258781
TI  - Why not sealants?

PMID- 8258782
TI  - Occlusal dental caries incidence and implications for sealant programs in a US
      college student population.
AB  - Given the decline in dental caries incidence in preteens and young teenagers in
      the United States, a study of the incidence of dental caries in young adults (17
      23 years) was conducted to provide a descriptive epidemiologic picture of this
      "new" natural history of dental caries in the late and post-teenage years. A
      retrospective study was performed analyzing the detailed dental records of the
      four-year college experience in the class of 1989, US Coast Guard Academy.
      Occlusal caries incidence, in the absence of associated proximal caries, was
      shown to be moderately common in molars (11.9%) and rare in premolars (0.8%). In
      contrast to previous studies' findings, demographic indicators, socioeconomic
      status indicators, and prior caries experience were poor predictors of occlusal
      caries incidence; targeting a universal sealant policy in this population
      therefore would be done best by tooth type rather than patient type. A
      preliminary cost-comparison model, projected over a 40-month period, suggests
      that the cost of initiating a universal molar sealant policy in this population
      would be 92 cents per year per student greater than the cost of restoring
      occlusal caries in the presence of sound proximal surfaces. This cost comparison
      suggests that it would be advantageous to initiate such a policy.

PMID- 8258783
TI  - Medical risk classification of dental patients in The Netherlands.
AB  - This study centers on the general health of dental patients, evaluated on the
      basis of the physical status classification system of the American Society of
      Anesthesiologists (ASA). A total of 4,087 patients completed a risk-related,
      patient-administered questionnaire. On the basis of their medical data, a
      computerized ASA classification was determined for each patient: 63.3 percent
      were in ASA class I, 25.7 percent in class II, 8.9 percent in class III, and 2.1
      percent in class IV. After verification and/or consultation with the physician,
      the dentist also determined the ASA class, and this was compared with the
      computerized outcome. The agreement expressed as a kappa value was 0.64; the
      computer result generally placed the patient in a higher category of medical
      risk. The computer-determined ASA classes differed among the various dental
      practices (chi 2 = 262.9; df = 138; P < .01). It is possible to estimate the risk
      class of dental patients on the basis of standardized medical information only;
      however, the definitive ASA class can only be determined after verification of
      the patient's reply or, in some cases, after consultation with a physician.

PMID- 8258785
TI  - Increased seroprevalence of hepatitis B in dental personnel necessitates
      awareness of revised pediatric hepatitis B vaccine recommendations.
AB  - This article presents data regarding occurrence of hepatitis B in health care
      workers and children living in their households. Also reviewed are recent
      revisions in pediatric hepatitis B vaccine recommendations. The purpose of this
      discussion is twofold: to provide information to assist dental personnel in the
      decision-making process regarding vaccination of infants, children, and
      adolescents in their households; and to increase knowledge to facilitate
      educational presentations. In the United States from 1979 to 1989 the prevalence
      of new acute hepatitis B cases increased by 37 percent. An estimated 1.25 million
      people with chronic hepatitis B are capable of infecting those within their
      immediate environment, including their families. Studies indicate that dental
      health care workers, through occupational exposure, may have a 10 times greater
      risk of becoming a chronic hepatitis B carrier than the average citizen. The
      World Health Organizations's Expanded Programme on Immunizations recommends that
      children receive vaccination in populations where hepatitis B is prevalent. The
      three-pronged approach for reducing pediatric transmission includes: (1)
      vaccination of infants born to infected mothers, (2) routine vaccination of
      children born to hepatitis-seronegative mothers, (3) identification and
      vaccination of specific groups of adolescents. Comprehension of these changes may
      increase compliance regarding vaccination of children in our household, as well
      as enhancing our educational presentations to patients, the community, and
      professional societies.

PMID- 8258784
TI  - Comparison of oral health ratings by dentists and dentate elders.
AB  - Previous studies suggest a discrepancy between the way dentists and patients
      measure oral health. The purpose of this study was to determine the relationship
      between a dentist's rating of an older dentate person's oral health and the
      patient self-rating using a single-item indicator, and to compare the clinical
      (i.e., number of teeth, caries, etc.) and subjective (problems with function,
      pain, etc.) factors that influence the rating. The study sample consisted of 776
      older dentate people. Results showed that dentists judged subjects' oral health
      significantly more positively than the self-ratings. Approximately 30 percent of
      the elders rated their oral health identically to the dentist and half rated
      their oral health lower than the dentist. Bivariate comparisons showed that
      similar clinical and subjective variables were associated with the dentist and
      patient ratings. Multiple regression findings, however, highlighted differences
      in the factors that influenced the ratings. In addition, the proportion of
      variance accounted for by the clinical factors as opposed to the subjective
      factors was greater for the dentist rating (R2 = .28 of .33) than the subject
      self-rating (R2 = .18 of .43).

PMID- 8258786
TI  - The use of a rapid enzymatic assay in the field for the detection of infections
      associated with adult periodontitis.
AB  - There are few objective assays for studies of the epidemiology of periodontal
      diseases. The PerioScan is an assay capable of detecting three periodontal
      pathogens, namely T. denticola, P. gingivalis, and B. forsythus, which have been
      associated with adult periodontitis. The PerioScan was tested in a sample of 301
      Brazilians. Clinical indices--bleeding, probing depth, gingival index, and
      periodontal index--were recorded from four sites in each subject. Subgingival
      plaque samples were collected from those sites and placed on the PerioScan card.
      Color results were scored in the field after 15 minutes. The plaque samples were
      screened with polyclonal antibodies for the three species by an ELISA system. The
      PerioScan, when compared with the ELISA system, yields a sensitivity of 91
      percent, specificity of 89 percent, and an accuracy of 90 percent. When the
      PerioScan was compared to clinical indices, there was a high sensitivity (at
      least 93%) and a low specificity (no less than 47%), with an accuracy of at least
      61 percent.

PMID- 8258787
TI  - Community-based sealant programs in the United States: results of a survey.
AB  - The appropriate use of pit and fissure sealants could reduce substantially the
      majority of occlusal caries among US school-aged children. The 1986-87 national
      oral health survey conducted by the NIDR showed that less than 8 percent of the
      children 5-17 years of age had sealants on their teeth. The purpose of this
      national study was to document the current status of community-based sealant
      programs and to identify general program characteristics. Data were gathered
      through a mail survey to all state dental directors and site visits to four
      selected comprehensive community-based programs. Twenty-nine states were
      currently conducting sealant programs. The vast majority of these programs had
      formal quality assurance systems and companion health education components. Eight
      states indicated that sealant programs had been terminated within the last two
      years. Medicaid reimbursement for sealants was available in 42 states, with a
      mean reimbursement rate of $10.71 per sealant. Reimbursement rates ranged from
      $3.00-$20.00 per sealant. State practice acts almost uniformly permitted the
      placement of sealants by dental hygienists (n = 48), but less frequently by
      dental assistants (n = 15). Approximately 43 percent of state practice acts did
      not require a dentist to be present physically when auxiliaries place sealants in
      public/community sealant programs. All respondents indicated that there was a
      need for additional programs in their state. No structural factors--for example,
      level of Medicaid reimbursement for sealants or state practice act requirements
      for auxiliary supervision--were found to be associated with the presence of
      community-based sealant programs. Nationally, only a small percentage of children
      appeared to be receiving sealants in community programs.

PMID- 8258788
TI  - Factors associated with fissure sealant delegation: dentist characteristics and
      office staffing patterns.
AB  - The purpose of this research was to identify dentist characteristics and dental
      office staffing patterns related to delegation of sealant applications. Results
      from a 1989 mailed survey were used to characterize Michigan general dentists (N
      = 300) who did or did not delegate sealant applications to auxiliaries and to
      identify factors associated with delegation. Nearly 50 percent of respondents
      were applying all sealants themselves. In offices that delegated the procedure,
      the mean proportion of sealants being applied by dentists was 39.9 percent.
      Registered dental hygienists were applying 51 percent, while registered dental
      assistants were applying 6.5 percent. Delegating dentists were more knowledgeable
      about sealant procedures, held more favorable attitudes, treated more young
      patients, placed more sealants, and were better informed about the legality of
      delegation according to the state practice act. Logistic regression analysis
      found that employing a registered dental hygienist was the most significant
      factor associated with sealant delegation, followed by employing a registered
      dental assistant. Findings suggest that dental auxiliaries, and particularly
      registered dental assistants, are underutilized for applying sealants. Approaches
      to increasing delegation of sealants may include changing dentists' traditional
      hiring patterns, highlighting the skills of auxiliaries such as the registered
      dental hygienist (RDH) and the registered dental assistant (RDA), and increasing
      awareness of legally allowable procedures that RDHs and RDAs can perform.

PMID- 8258789
TI  - Collecting state-level oral health data when resources are limited: an approach
      to oral health surveillance.
AB  - Many states and localities do not have the resources to conduct oral health
      surveys of their whole populations, but the demands for data collection continue
      to increase for both program administration and for Maternal and Child Health
      Block Grant funding. As one response to this problem, the Oral Health Program of
      the Michigan Department of Public Health developed an oral health surveillance
      system as a low-cost method of collecting usable data from the service
      populations of local health agencies providing direct patient care in Michigan. A
      record form, to be completed by dentists or hygienists in those agencies at
      initial or recall examinations, was developed and pilot-tested for all patients
      of target age groups who presented over a specified four-week period. This paper
      gives the results from 19 agencies that participated in the pilot test in
      Michigan. Results showed that 40.5 percent of 2-5-year-olds (n = 341) had some
      caries experience, their d/dft was 78.2 percent, and mean dft was 4.8 (SD +/-
      3.5). Among the 6-19-year-olds (n = 710), 61.4 percent had experienced caries,
      the D/DFT was 41.8 percent, and the mean DFT was 4.2 (SD +/- 3.2). Among the
      adults examined, 45.1 percent of 20-64-year-olds (n = 820) and 38.1 percent of
      those 65 years or older (n = 105) had two or more teeth with untreated decay.
      These data suggest a high level of untreated disease among the service
      populations of the local dental health agencies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258790
TI  - Delivery of oral health care through the Ryan White CARE Act to people infected
      with HIV.
AB  - The Ryan White Comprehensive AIDS Resources Emergency (CARE) Act of 1990 was
      passed by Congress "to improve the quality and availability of care for
      individuals and families with HIV disease." The act targets those individuals
      infected with HIV who lack financial resources to pay for care. While provision
      of oral health care is not mandated by the legislation, many oral health services
      are supported through five different programs receiving CARE Act funding.
      Legislative mandates, program guidance materials, grant applications, and other
      related materials were reviewed to analyze oral health care services supported or
      proposed through the CARE Act. In fiscal year 1991, an estimated $5.8 million of
      the total CARE Act funds ($229.6 million) were used for oral health care, and
      there is evidence that oral health concerns will receive increasing attention by
      grantees in future years. Opportunities exist for local oral health professionals
      to become involved in CARE Act programs and in the priority development process.
      It is possible that CARE Act grantees will serve as catalysts for the development
      of partnerships between private practitioners and public sector programs-
      relationships that could lead to improved access and quality of care for people
      with HIV infection.

PMID- 8258792
TI  - The genius of disease.

PMID- 8258791
TI  - Growth factors, antagonists and lung cancer.

PMID- 8258793
TI  - The mining disaster of Borken, the implementation of a 3-year support programme
      and the help through EuroActDIS.

PMID- 8258794
TI  - Psychological impact of body recovery duties.
AB  - The psychological effects of body recovery duties were studied in two groups, 28
      specialized police volunteers and 40 ambulance workers. The Impact of Events
      scale and the General Health Questionnaire were administered to both groups. The
      results showed that 20% of the ambulance workers and 3% of the policemen were in
      the moderate to severe category of psychological distress. In neither group did
      age, number of incidents attended or years in service correlate with distress.
      Possible causes of the difference between the two groups, such as the way they
      were managed, are discussed.

PMID- 8258795
TI  - Breast reconstruction at a district general hospital.
AB  - Breast reconstruction is normally carried out by plastic surgeons, but the advent
      of permanent tissue expanders places post-mastectomy reconstruction within easy
      reach of the general surgeon. Nineteen patients underwent breast reconstruction
      between 1989 and 1991 using a subpectoral silicone-based, double lumen tissue
      expander. Assessment of results was by: (a) patient completed questionnaire; and
      (b) third party evaluation of standardized photographs. The mean operating time
      was 58 min (40-80 min) and mean hospital stay 3 days (2-7 days). Complications
      included one flap necrosis and one leaking injection port. Outpatient tissue
      expansion required an average of seven visits (4-11) and was completed in an
      average of 12 months (7-19). The injection port was subsequently removed under
      local anaesthetic as a day case. The fully dressed appearance following
      reconstruction was graded good or excellent by 100% of patients and in over 80%
      of third-party assessments. Equivalent figures for the appearance when wearing a
      bra were 93% and 60% and undressed 57% and 47%, respectively. All patients
      recommended the procedure but 25% found inflation uncomfortable. Subpectoral
      tissue expansion is a safe, cosmetically acceptable method of breast
      reconstruction which is associated with a high level of patient satisfaction.

PMID- 8258796
TI  - Temporary prostatic stenting and androgen suppression: a new minimally invasive
      approach to malignant prostatic retention.
AB  - Urinary retention secondary to carcinoma of the prostate is usually treated by
      'channel' transurethral resection of the prostate either performed alone or in
      combination with hormone manipulation. The combination of temporary prostatic
      stenting and androgen suppression may reduce the morbidity and mortality
      associated with this treatment. We report on our initial experience using the
      combination of a temporary prostatic stent with the oral anti-androgen Flutamide
      in 10 patients with urinary retention or severe bladder outflow obstruction
      secondary to prostatic carcinoma. Eight of the ten patients successfully voided
      and maintained normal voiding after stent removal. There were two treatment
      failures requiring prostatic resection. We believe the cost of stenting and
      medication is entirely justified by patient preference and clearance of hospital
      beds.

PMID- 8258797
TI  - Extra-articular tenodesis for anterior cruciate deficient knees: a review of the
      Ellison repair.
AB  - Twenty-two patients who underwent an Ellison extra-articular tenodesis for
      anterolateral instability of the knee, performed by one surgeon (SCC), have been
      reviewed after a mean follow-up of 59 months. Seventy-seven per cent had a good
      or excellent result enabling them to return to their pre-injury level of sport.
      These results compare very favourably with intra-articular repair but are not
      associated with such severe complications.

PMID- 8258798
TI  - SPECT imaging in the diagnosis of meniscal tears.
AB  - Sixty patients scheduled for arthroscopy of a knee because of suspected meniscal
      tears had preoperative planar and single photon emission computed tomography
      (SPECT) radionuclide scans. A crescentic pattern of uptake on the SPECT
      transaxial view was used as a criterion for diagnosing a tear of a meniscus. The
      sensitivity of the investigation was 77%, specificity 74%, negative predictive
      value (NPV) 65%, positive predictive value (PPV) 83%, and accuracy 76%. Tears of
      the posterior horn of the cartilage were also associated with intense focal
      uptake on the transaxial view as well as increased equilibrium activity in the
      adjacent femoral condyle. When these appearances were included as additional
      criteria the sensitivity rose to 90%, NPV 81%, and accuracy 84%. This study
      confirms the usefulness of SPECT imaging in identifying meniscal tears.

PMID- 8258799
TI  - Delay in presentation after myocardial infarction.
AB  - Thrombolytic therapy reduces mortality in acute myocardial infarction (AMI),
      giving maximal benefit with early treatment. In the UK delayed presentation after
      AMI may reduce the advantages of thrombolysis. To assess this, 103 patients
      presenting with AMI to two London Hospitals were interviewed to determine the
      length and cause of delay from onset of chest pain to arrival at hospital. Forty
      nine per cent of patients took longer than 2 h to arrive at hospital, and 21%
      took longer than 4 h. Patients who contacted their general practitioner (GP) had
      a significantly prolonged time delay (160 mins; 65-730: median; range) compared
      to those who went directly to hospital by ambulance (82 mins; 15-395; P <
      0.0005), or on their own (90 min; 15-855; P < 0.005). Patients calling their GP
      took a similar duration to decide to seek help [decision time (30 min versus 25
      mins) P = NS], but significantly longer to reach hospital once the decision was
      made (110 min versus 56 min; P < 0.0001), than those proceeding directly to
      hospital. Believing the pain was cardiac in origin significantly shortened
      decision time (15 min versus 45 min; P < 0.05), as did knowledge of the existence
      of thrombolysis (15 min versus 50 min; P < 0.05) and lack of prior cardiac
      symptoms (18 min versus 42 min; P < 0.05). Only 14% were aware of thrombolysis.
      Rank correlation confirmed that decision and total delay time were age
      independent. Delays of this magnitude may compromise the efficiency of
      thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258800
TI  - Perceived religiousness is protective for colorectal cancer: data from the
      Melbourne Colorectal Cancer Study.
AB  - The perceived or self-reported degree of 'religiousness' was obtained by
      interview from 715 colorectal cancer patients and 727 age/sex matched community
      controls, as part of a large, comprehensive population-based study of colorectal
      cancer incidence, aetiology and survival (The Melbourne Colorectal Cancer Study)
      conducted in Melbourne, Australia. Self-reported or perceived 'religiousness', as
      defined in the study, was a statistically significant protective factor [relative
      risk (RR) = 0.70, 95% confidence interval (CI) = 0.6-0.9, P = 0.002]. This
      statistically significant protection remained after the previously determined
      major risk factors found in the study, namely a family history of colorectal
      cancer, dietary risk factors, beer consumption, number of children and age at
      birth of the first child, were statistically corrected for (P = 0.004). There was
      no association between Dukes' staging of the cancer and perceived degree of
      'religiousness' (P = 0.42). Although self-reported or perceived 'religiousness'
      was associated with a median survival time of 62 months compared with 52 months
      in those self-reporting as being 'non-religious', this difference was not
      statistically significant (P = 0.64).

PMID- 8258801
TI  - Legal accountability for the provision of medical care: a comparative view.

PMID- 8258802
TI  - Paracelsus: a quincentennial assessment.

PMID- 8258803
TI  - Medicine and music in Vienna at the time of Mozart.

PMID- 8258804
TI  - James Young Simpson: the controversy surrounding the presentation of his Air
      Tractor (1848-1849).

PMID- 8258805
TI  - Hypophosphataemic osteomalacia due to urinary kappa light chain.

PMID- 8258806
TI  - Patchy speckled bath PUVA pigmentation.

PMID- 8258807
TI  - The Dambusters: a case of cerebrospinal and urinary obstruction.

PMID- 8258808
TI  - Carcinoid syndrome due to a primary ovarian carcinoid tumour.

PMID- 8258809
TI  - Beethoven's demise.

PMID- 8258810
TI  - Enterostomy feeding.

PMID- 8258811
TI  - Charles Dickens: orthopaedics and the handicapped.

PMID- 8258812
TI  - Europe and the tropics.

PMID- 8258813
TI  - The diagnosis of thoracic foregut duplication cysts.

PMID- 8258814
TI  - Successful but complex drainage of pancreatic abscess.

PMID- 8258815
TI  - Waterhouse-Friderichsen syndrome resulting from colchicine overdose.

PMID- 8258816
TI  - Cigarette smoking increases white blood cell aggregation in whole blood.

PMID- 8258817
TI  - Conjoined twins.

PMID- 8258818
TI  - Glue ear.

PMID- 8258819
TI  - Sugar and coronary heart disease: a molecular explanation.

PMID- 8258820
TI  - A novel series of selective, non-peptide inhibitors of angiotensin II binding to
      the AT2 site.
AB  - The availability of peptide and non-peptide Ang II receptor antagonists has
      permitted the study of Ang II receptor heterogeneity. It is now widely recognized
      that there are at least two distinct Ang II receptor subtypes. AT1 receptors are
      selective in their recognition of agents such as losartan, DuP 532, L-158,809,
      SK&F108566, and similar non-peptides. To date, all of the well-known actions of
      Ang II in mammals are blocked by the AT1 selective antagonists such as losartan
      and are thus designated as being mediated by the AT1 receptor. Although there
      have been reports of functional activity mediated through AT2 sites, the
      pharmacological role for the AT2 receptor has not yet been elucidated. Herein, we
      report the chemistry and SAR on a novel series of 1,2,3,4-tetrahydrosioquinoline
      3-carboxylic acids which have selective affinity for AT2 receptors. The most
      potent of which (19) has an IC50 of 30 nM for the AT2 receptor in the rat adrenal
      radioligand binding assay.

PMID- 8258821
TI  - Nanomolar-affinity, non-peptide oxytocin receptor antagonists.
AB  - Non-peptide antagonists of the peptide hormone oxytocin (OT) with nanomolar OT
      receptor affinities are described. These compounds incorporate novel amido- and
      amidoalkylcamphor variations to the lead structure L-366,509 (1) to achieve
      receptor affinity enhancements of 2-3 orders of magnitude over that compound. The
      new OT antagonist L-367,773 (35) is shown to be an orally bioavailable agent with
      good duration in vivo and to inhibit OT-stimulated uterine contractions
      effectively in several in vitro and in vivo models.

PMID- 8258822
TI  - Three-dimensional quantitative structure-activity relationships of 5-HT receptor
      binding data for tetrahydropyridinylindole derivatives: a comparison of the
      Hansch and CoMFA methods.
AB  - A series of new derivatives of 3-(1,2,5,6-tetrahydropyridin-4-yl)indole (4-THPI)
      has been synthesized, and their dissociation constants at the 5-HT1A and 5-HT2
      serotonin (5-HT) receptor subtypes have been determined. The new data were
      combined with similar binding data on a related set of THPI analogs reported
      previously (Taylor et al. Mol. Pharmacol. 1988, 34, 42-53) and used to develop 3
      dimensional quantitative structure-activity relationships (3-D QSARs) for these
      compounds at the 5-HT1A and 5-HT2 receptor sites, by the method of comparative
      molecular field analysis (CoMFA). Since the previous study included several
      conventional QSARs obtained by Hansch analysis, and the new compounds in some
      cases fall within the congeneric series used in those analyses, we were able to
      make a direct comparison of the predictive capabilities of CoMFA and Hansch
      analysis using identical training and test data sets. The overall quality of
      actual predictions of activity by both methods appears to be about the same, as
      assessed by the root mean square (rms) residuals between actual and predicted pKi
      values. On the one hand, the compounds most poorly predicted by the Hansch
      analysis were 34, 35, and 37, while compounds 30-33 were relative poorly
      predicted by CoMFA. However, a clear advantage of CoMFA is the ability to include
      diversely substituted or noncongeneric analogs that must be omitted from
      conventional QSAR analysis. Using the entire data set of 45 THPI analogs reported
      here, pKi predictions for six additional compounds having 5-heteroarylindole
      substituents gave rms residuals of 0.46 and 0.36 for the 5-HT1A and 5-HT2 models,
      respectively; this is close to the experimental error of the binding data. The
      significance of the CoMFA field graphs in terms of molecular features required
      for activity and selectivity at these 5-HT receptor subtypes is discussed.

PMID- 8258823
TI  - Xanthines with C8 chiral substituents as potent and selective adenosine A1
      antagonists.
AB  - Several 8-substituted 1,3-dipropylxanthines were synthesized, and their receptor
      binding affinities at adenosine A1 and A2 receptors were measured. When
      enantiomeric pairs of compounds were examined, the R enantiomers were
      significantly more potent than the corresponding S enantiomers. The most potent
      compound at the A1 receptor was (R)-3,7-dihydro-8-(1-methyl-2-phenylethyl)-1,3
      dipropyl-1H-purine-2,6-di one (5a; MDL 102,503), whose Ki value at the A1
      receptor was 6.9 nM. However, a more selective compound was (R)-3,7-dihydro-8-(1
      phenylpropyl)-1,3-dipropyl-1H-purine-2,6-dione (5d; MDL 102,234), which had a Ki
      value of 23.2 nM at the A1 receptor and an A2/A1 ratio of 153.

PMID- 8258824
TI  - Antioxidant and neutrophil-inhibiting properties of new 2-O-methyl-6
      (alkylthio)ascorbic acid derivatives.
AB  - A series of new 6-(alkylthio)ascorbic acids was synthesized, and their inhibitory
      effects on lipid peroxidation and the oxidative burst of human neutrophils were
      tested. Of 12 structurally different lipophilic ascorbic acid derivatives 6-S-n
      hexadecyl-2-O-methyl-6-deoxy-6-thio-L-ascorbic acid (7b; B-003) inhibited the
      Fe2+/ADP-induced lipid peroxidation of rat liver microsomes with an IC50 value of
      2 microM. In human neutrophils, 7b most potently inhibited the fMLP-induced
      oxidative burst in a cell density-dependent manner with an IC50 value of 0.6
      microM at 5 x 10(5) cells/mL. Shorter alkyl chain lengths decreased the
      inhibitory potency for both lipid peroxidation and oxidative burst, but in
      general no correlation was found between the two parameters. Likewise, 6-S-n
      hexadecyl-3-O-methyl-6-thio-L-ascorbic acid (7c; B-015), the regioisomer of 7b,
      was a potent antioxidant but did not affect the oxidative burst. Since superoxide
      anions generated by xanthine/xanthine oxidase were not quenched by 7b, it became
      evident that its target was somewhere between receptor stimulation and NADPH
      oxidase activation. By measuring the cellular concentrations of 7b and 7c, an
      accumulation of the first was found explaining its potency and the dependence on
      cell density. Expecting a pKa value of 3.3 for 7b and 7.7 for 7c a protonophore
      action of 7b was likely and could be verified by the drop in intracellular pH
      (pHi) which did not occur with 7c. Ionophores such as nigericin, CCCP, or
      propionic acid also lowered the pHi but did not inhibit the oxidative burst,
      indicating that the pHi drop was not the cause for this inhibition. 7b also
      strongly inhibited the fMLP-induced secretion of azurophilic (IC50 = 7 microM)
      and specific (IC50 = 2.5 microM) granules.

PMID- 8258825
TI  - Synthesis of novel modified dipeptide inhibitors of human collagenase: beta
      mercapto carboxylic acid derivatives.
AB  - The synthesis of a series of thiol-containing, modified dipeptide inhibitors (8)
      of human collagenase, which incorporate various carboxylic acid derivatives at
      the presumed P1 position, beta to the thiol group, is described. The compounds
      were evaluated, in vitro, for their ability to inhibit the degradation of rat
      skin type 1 collagen by purified human lung fibroblast collagenase, and structure
      activity relationship studies are described. Optimum potency (IC50 values in the
      nanomolar range) was achieved by incorporating methyl (compounds 43a, 56a, and
      57ab) or benzyl esters (44a) at the P1 position. Small amides were also
      accommodated (e.g. primary amide 47a), but in general, increasing the size of the
      P1 amide substituent lowered potency. PheNHMe, TrpNHMe, and Tyr(Me)NHMe
      substituents were found to be approximately equipotent P2'-residues. The results
      of testing all four diastereoisomers 56a-d of the compound with (S)-TrpNHMe at
      the P2' position indicated that the S,S,S diastereoisomer 56a possessed highest
      potency (IC50 2.5 nM) and that the second most potent diastereoisomer was 56d
      (IC50 12 nM) with the R,R,S configuration. It appeared that the orientation of
      the P1' and the thiol-bearing centers to each other is a more critical influence
      on potency than any absolute stereochemical requirements. It is suggested that
      the high potency of the beta-mercapto carboxylic acid derivatives may be a
      consequence of bidentate coordination of the thiol and carbonyl groups to the
      active-site zinc ion in the collagenase enzyme.

PMID- 8258826
TI  - 6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor
      antagonists: synthesis, biological activity, and structure-activity
      relationships.
AB  - Starting from the recently reported nonpeptidic angiotensin II (AII) receptor
      antagonists DuP753 (1) and Exp 7711 (2), we have designed and investigated novel
      substituted benzimidazoles. Systemic variation of several substituents at the
      benzimidazole ring positions 4-7 led to the finding that substitution in position
      6 with acylamino groups results in highly active AII antagonists. Compounds with
      6-membered lactam or sultam substituents in position 6 of benzimidazole showed
      receptor activities in the low nanomolar range but were only weakly active when
      given orally to rats. In contrast, analogous substitution of the benzimidazole
      moiety with basic heterocycles resulted in potent AII antagonists which were also
      well absorbed after oral application. The most active compound of this series, 33
      (BIBR 277), was selected as a candidate for clinical development. On the basis of
      molecular modeling studies a binding model of this new class of AII antagonists
      to the AT1 receptor is proposed.

PMID- 8258827
TI  - Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase
      inhibition and bronchodilation. 1. 2-[2-(1-Imidazolyl)alkyl]-1(2H)
      phthalazinones.
AB  - A number of 4-substituted 2-[omega-(1-imidazolyl)alkyl]-1(2H)-phthalazinones were
      synthesized in order to develop agents possessing both thromboxane A2 synthetase
      inhibitory and bronchodilatory activities. The pharmacological evaluation of
      these compounds disclosed that they have both activities to various extents. Both
      activities were slightly dependent on the length of the 2-substituents and
      largely affected by the nature of the 4-substituents. Compounds bearing phenyl
      and thienyl groups exhibited relatively high and well-rounded activities. Among
      these compounds, 12j and 15f were found to be the most effective agents having
      well-rounded activities in vitro and in vivo. Introduction of a carboxyl group
      reduced both activities contrary to our expectation. 4-(3-Pyridyl)phthalazinone
      18b was of particular interest because of unexpectedly high in vivo activities in
      spite of an absence of significant in vitro activities.

PMID- 8258828
TI  - Novel antiasthmatic agents with dual activities of thromboxane A2 synthetase
      inhibition and bronchodilation. 2. 4-(3-Pyridyl)-1(2H)-phthalazinones.
AB  - A series of novel 4-(3-pyridyl)-1(2H)-phthalazinone derivatives which possess
      dual activities of thromboxane A2 (TXA2) synthetase inhibition and
      bronchodilation was synthesized, and their pharmacological activities were
      evaluated. While the length and the bulk of 2-alkyl substituents had no influence
      on either activity, the 2-substituents with polar groups reduced bronchodilatory
      activity. Furthermore, we introduced heteroaromatic nuclei into the 4-position of
      the phthalazinone and found that 1-imidazolyl (13a) and 5-thiazolyl (16b and 16c)
      derivatives were as active as the parent 3-pyridyl compound 5b. These findings
      suggest that heteroaromatic nuclei at the 4-position of phthalazinones play a
      critical role in TXA2 synthetase inhibition. Additionally, the hydrophobicity of
      the compounds was found to exert a marked influence on bronchodilatory activity.
      These observations led to the selection of 2-ethyl-4-(3-pyridyl)-1(2H)
      phthalazinone (5b) (KK-505) and 2-methyl-4-(5-thiazolyl)-1(2H)-phthalazinone
      (16b) (KK-562) for further studies. Although their precise mechanism of action
      remains unclear, this series of novel phthalazinone derivatives represents a new
      class of antiasthma agents with dual activities.

PMID- 8258829
TI  - 2-Substituted 5-methoxy-N-acyltryptamines: synthesis, binding affinity for the
      melatonin receptor, and evaluation of the biological activity.
AB  - A series of 2-substituted 5-methoxy-N-acyltryptamines was synthesized and their
      affinity for the melatonin receptor, isolated from whole quail brains, was tested
      in a succession of in vitro ligand-receptor binding experiments, using 2
      [125I]iodomelatonin as a labeled ligand. Optimization of the C2 substituent and
      the N-acyl group resulted in compounds having picomolar affinity for the receptor
      (vs nanomolar affinity for melatonin). In two tests for evaluation of the
      biological activity (effects on the spontaneous firing activity of single neurons
      in the rabbit parietal cortex in situ, and the Syrian hamster gonadal regression
      model in vivo) most of the analogs behaved as agonists. Isopropyl substitution at
      C2 alone, or concomitantly with cyclopropyl substitution at the N-acyl position,
      resulted in much lower affinity and weaker biological effect, or lack of activity
      in the latter case. Of interest are the compounds 4d (R = phenyl, R1 = CH3) and
      4g (R = phenyl, R1 = cyclopropyl), which expressed high affinity for the receptor
      and apparent antagonistic activity under the conditions of the experimental
      models employed, though the analog 4g (R = phenyl, (R1 = cyclopropyl) seemingly
      was a weak antagonist and in situ expressed mixed activity in the higher
      concentration range. Cyclopropyl substitution at the N-acyl position inevitably
      resulted in lower affinity for the receptor and weaker biological activity. These
      data demonstrate that the N-acetyl group is important for both affinity and
      agonist biological activity. The substituents at C2 are crucial for the affinity
      of the compound for the receptor and can be utilized to create putative high
      affinity agonists or antagonists.

PMID- 8258830
TI  - Further studies of the structure-activity relationships of 1-[1-(2
      benzo[b]thienyl)cyclohexyl]piperidine. Synthesis and evaluation of 1-(2
      benzo[b]thienyl)-N,N-dialkylcyclohexylamines at dopamine uptake and phencyclidine
      binding sites.
AB  - We previously reported (J. Med. Chem. 1993, 36, 1188-1193) that changes to the
      ring size of the piperidine and cyclohexyl rings of the high-affinity and
      selective dopamine (DA)-uptake inhibitor 1-[1-(2
      benzo[b]thienyl)cyclohexyl]piperidine (BTCP, 2) caused different, and in some
      cases opposite, changes in affinity for sites on the DA transporter labeled by
      [3H]BTCP and [3H]-cocaine. These results suggested that the radioligands label
      different sites on the transporter. In the present study, we extend the structure
      activity relationships (SAR) of BTCP by studying the binding characteristics of a
      series of N,N-disubstituted 1-(2-benzo[b]thienyl)cyclohexylamines 7-32 at the DA
      transporter. Cyclohexyl was selected as opposed to other ring sizes since it
      corresponds to BTCP. The binding results indicate that a considerable degree of
      structural variation is permitted for the N-substituents, while still retaining
      nanomolar affinity for sites on the transporter (studied in rat forebrain
      homogenates). As observed in our earlier study, the differential effects of
      structural change on binding to sites on the DA transporter labeled by these
      radioligands suggests that they are different and distinct binding sites. In
      general, and up to a point, increasing the size and lipophilicity of the N
      substituents resulted in improvements in binding but appeared to have less
      predictable effects on DA-uptake inhibition (as measured in rat brain
      synaptosomes). The binding of these compounds to sites labeled by [3H]BTCP
      appeared to correlate best with IC50 for DA-uptake inhibition. To our surprise,
      the monoalkyl N-substituted BTCP derivatives displayed the highest affinity for
      the DA transporter of all the compounds in this series. For example, the N
      (cyclopropylmethyl) derivative 14 displayed IC50's = 23 nM ([3H]cocaine) and 1 nM
      ([3H]-BTCP), and the N-butyl derivative 10 showed IC50's = 60 nM ([3H]cocaine)
      and 0.3 nM ([3H]-BTCP). BTCP exhibited IC50's of 39 nM ([3H]cocaine) and 5 nM
      ([3H]BTCP) in this assay. The observation that N,N-dibutyl derivative 31
      exhibited low ratios of IC50 [3H]cocaine/IC50 DA reuptake and IC50 [3H]BTCP/IC50
      DA reuptake suggests that it may be a potential candidate for cocaine antagonism
      studies. The effect of additional amino, amide, and aromatic groups on the N
      substituents was examined, and the results are discussed. The failure of all of
      the compounds in this series to bind phenycyclidine receptors coupled with their
      high affinity and range of selectivities at the DA transporter identifies many of
      them as useful tools for probing the mode of action of BTCP at this site.

PMID- 8258831
TI  - Glucosidase inhibitors: structures of deoxynojirimycin and castanospermine.
AB  - High-resolution structures of the glucosidase inhibitors deoxynojirimycin (dNM)
      and castanospermine (CAST) have been determined by X-ray diffraction. The crystal
      parameters are a = 10.751(3) and 8.788(3) A, b = 9.263(3) and 8.172(3) A, c =
      7.719(2) and 6.507(2) A, and space group P2(1)2(1)2(1) and P2(1) for dNM and
      CAST, respectively. (beta = 105.44(8) degrees for CAST.) The absolute
      configuration of CAST has also been established. Stereochemical comparisons with
      natural glucosidase substrates such as maltose and methyl glucoside show great
      similarities in the positioning of functional groups, and indicate the basis for
      enzyme inhibition. Conformational comparison between dNM and CAST suggests the
      greater activity of CAST may be due to the fixed axial positioning of the O6
      atom; the results have implications for the design of analogues for potential
      anti-HIV and other antiviral therapies.

PMID- 8258832
TI  - Endothelin-1 analogues substituted at both position 18 and 19: highly potent
      endothelin antagonists with no selectivity for either receptor subtype ETA or
      ETB.
AB  - Novel endothelin-1 (ET-1) analogues which are highly potent endothelin
      antagonists at both receptor subtype ETA and ETB are reported. The replacement of
      Asp18 with the Thr18 and of Ile19 with a hydrophobic amino acid whose side-chain
      branches on the gamma-carbon such as Leu, cyclohexylalanine, and gamma
      methylleucine (gamma-MeLeu) resulted in loss of or significantly decreased the
      biological activity of ET-1, while high affinity for the ETA (IC50 = 0.42-0.70
      nM) and ETB (IC50 = 0.17-0.43 nM) receptor was retained. These compounds were
      shown to have high antagonist activities in ET-1-induced vasoconstriction of
      porcine coronary artery (pA2 7.4-7.7) and in Sarafotoxin S6c-induced
      vasoconstriction of rabbit pulmonary artery ([Thr18, gamma-MeLeu19]ET-1: pA2
      8.4). Among these compounds, [Thr18, gamma-MeLeu19]ET-1 has the desirable
      characteristic of possessing no agonist activity at either receptor subtype.

PMID- 8258833
TI  - Synthesis and structure-activity studies of a series of
      [(hydroxybenzyl)amino]salicylates as inhibitors of EGF receptor-associated
      tyrosine kinase activity.
AB  - The synthesis and structure-activity relationships of a series of
      [(hydroxybenzylidene)amino]salicylates and a series of
      [(hydroxybenzyl)amino]salicylates as inhibitors of EGF receptor-associated
      tyrosine kinase activity are described. Their inhibitory potency was evaluated in
      vitro using ER 22 cell membranes (CCL 39 cells transfected with EGF receptor) as
      an enzyme source and the tridecapeptide RRSrc (RRLIEDAEYAARG) as substrate. Their
      cellular activity was measured by inhibition of the EGF-stimulated DNA synthesis
      of ER 22 cells. Chemical modifications were made to analyze the role of the
      different substituents. The amino series was found to be more active than the
      imino series. The hydroquinone moiety appears to be essential for tyrosine kinase
      inhibitory activity in the series of 5-[(2,5-dihydroxybenzyl)amino]salicylates.
      Comparison of the imino and amino series by molecular modeling techniques
      provides further evidence in support of the hypothesis that the important reduced
      linking chain, CH2NH, allows the correct positioning of the 2,5-dihydroxybenzyl
      ring, possibly in a cis-like conformational arrangement.

PMID- 8258834
TI  - Antipsoriatic anthrones with modulated redox properties. 1. Novel 10-substituted
      1,8-dihydroxy-9(10H)-anthracenones as inhibitors of 5-lipoxygenase.
AB  - The syntheses, the biological evaluation, and the structure-activity
      relationships of a novel series of 1,8-dihydroxy-9(10H)-anthracenones bearing
      acyl-, alkyl-, or alkylidene-linked aromatic substituents in the 10-position are
      described. The phenylacyl and phenylalkylidene analogs were far more potent
      inhibitors of 5-lipoxygenase (5-LO) from bovine polymorphonuclear leukocytes
      (IC50 values in the 10(-7) M range) than the antipsoriatic drug anthralin,
      whereas phenylalkyl analogs were only weak inhibitors. Among the active compounds
      were both potent generators of hydroxyl radicals, as determined by deoxyribose
      degradation, and strong reducers of the stable free radical 2,2-diphenyl-1
      picrylhydrazyl (DPPH). However, several derivatives of this series maintained 5
      LO inhibitory activity but did not generate hydroxyl radicals and were not
      reactive with DPPH. In particular, phenylacyl analogs were also 6 times more
      efficient in inhibition of lipid peroxidation in model membranes than anthralin.
      Structure-activity relationships have shown that the presence of free phenolic
      groups in the attached aromatic ring is beneficial but not required for 5-LO
      inhibitory potency. The inhibitory potency in the 10-phenylacyl series increased
      with the length of the acyl chain with three methylene units being the optimum,
      suggesting a specific enzyme interaction which would not be expected for
      nonspecific redox inhibitors.

PMID- 8258835
TI  - Design of antineoplastic agents on the basis of the "2-phenylnaphthalene-type"
      structural pattern. 2. Synthesis and biological activity studies of
      benzo]b]naphtho[2,3-d]furan-6,11-dione derivatives.
AB  - Based on the "2-phenylnaphthalene-type" structural pattern hypothesis developed
      in our laboratory, a number of benzo[b]naphtho[2,3-d]furan-6,11-diones were
      designed, synthesized, and evaluated in vitro for their inhibitory action against
      the growth of human promyelocytic leukemia cells (HL-60), small-cell lung cancer
      (SCLC), SCLC cells resistant to cisplatin (SCLC/CDDP), National Cancer
      Institute's disease-oriented primary antitumor 60 cell-line panel, and drug
      stimulated topoisomerase II-mediated DNA cleavages. Many compounds designed were
      found to possess potent activity in one or more of the biological tests. In
      general, activity found in one of the cell lines tested is often echoed in other
      cell lines and many also expressed substantial inhibitory activity against
      topoisomerase II-mediated cleavage activities. One of these compounds, 3-[2
      (dimethylamino)ethoxy]-1-hydroxybenzo[b]naphthol[2,3-d]furan- 6,11-dione (8j),
      exhibited strong inhibitory activity throughout the entire series of test panel.
      Thus, it appears that the proposed structural pattern hypothesis has received
      substantial support through experimental verification.

PMID- 8258836
TI  - Synthesis and biological evaluation of N4-substituted imidazo- and v-triazolo[4,5
      d]pyridazine nucleosides.
AB  - The chemical synthesis of certain N4-substituted imidazo[4,5-d]pyridazine and v
      triazolo[4,5-d]-pyridazine nucleosides is described. In both series, the 4-chloro
      analogues, i.e., 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazo[4,5
      d]pyr idazine (5a) and 4-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-v
      triazolo[4,5- d]pyridazine (5b), were used as synthons to the target nucleosides.
      Nucleoside 5b was far more reactive toward nucleophilic displacements than 5a.
      Attempted deprotection of 5b was always accompanied with displacement of the 4
      chloro substituent, whereas 5a was conveniently deacetylated without loss of the
      chloro group. Biological evaluation of the title nucleosides included antitumor
      studies and substrate/inhibition studies with certain purine-metabolizing
      enzymes. The corresponding adenosine analogues, i.e., 2-aza-3-deazaadenosine (6a)
      and 2,8-diaza-3-deazaadenosine (6b), were very slowly reacting substrates and
      weak inhibitors of bovine adenosine deaminase, whereas the inosine analogues were
      highly resistant to human purine nucleoside phosphorylase. The 4-benzylamino
      derivatives were weak inhibitors of adenosine transport into human erythrocytes.
      The inosine, adenosine, and selected N4-substituted analogues exhibited no in
      vitro toxicity toward murine L1210 leukemia and B16 melanoma cells.

PMID- 8258837
TI  - (1-Butyl-4-piperidinyl)methyl 8-amino-7-chloro-1,4-benzodioxane-5-carboxylate
      hydrochloride: a highly potent and selective 5-HT4 receptor antagonist derived
      from metoclopramide.

PMID- 8258838
TI  - Novel pharmacologic therapies in the treatment of experimental traumatic brain
      injury: a review.
AB  - Delayed or secondary neuronal damage following traumatic injury to the central
      nervous system (CNS) may result from pathologic changes in the brain's endogenous
      neurochemical systems. Although the precise mechanisms mediating secondary damage
      are poorly understood, posttraumatic neurochemical changes may include
      overactivation of neurotransmitter release or re-uptake, changes in presynaptic
      or postsynaptic receptor binding, or the pathologic release or synthesis of
      endogenous "autodestructive" factors. The identification and characterization of
      these factors and the timing of the neurochemical cascade after CNS injury
      provides a window of opportunity for treatment with pharmacologic agents that
      modify synthesis, release, receptor binding, or physiologic activity with
      subsequent attenuation of neuronal damage and improvement in outcome. Over the
      past decade, a number of studies have suggested that modification of postinjury
      events through pharmacologic intervention can promote functional recovery in both
      a variety of animal models and clinical CNS injury. This article summarizes
      recent work suggesting that pharmacologic manipulation of endogenous systems by
      such diverse pharmacologic agents as anticholinergics, excitatory amino acid
      antagonists, endogenous opioid antagonists, catecholamines, serotonin
      antagonists, modulators of arachidonic acid, antioxidants and free radical
      scavengers, steroid and lipid peroxidation inhibitors, platelet activating factor
      antagonists, anion exchange inhibitors, magnesium, gangliosides, and calcium
      channel antagonists may improve functional outcome after brain injury.

PMID- 8258839
TI  - A phase II study of moderate hypothermia in severe brain injury.
AB  - Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale
      (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to
      standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The
      two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95),
      randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was
      begun within 6 h of injury by use of cooling blankets. Metocurine and morphine
      were given hourly during induction and maintenance of hypothermia. Rewarming was
      at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature
      had reached 33 degrees C. Muscle relaxants and sedation were continued until core
      temperature reached 35 degrees C. There were no cardiac or coagulopathy-related
      complications. Seizure incidence was lower in the hypothermia group (Fisher's
      exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group,
      but difference was not statistically significant (chi-square test). Mean Glasgow
      Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of
      16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate
      Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead
      (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic
      outcome with minimal toxicity, we believe that phase III testing of moderate
      systemic hypothermia in patients with severe head injury is warranted.

PMID- 8258840
TI  - Effects of ethanol in traumatic brain injury.
AB  - The effects of ethanol intoxication on brain injury and cerebral blood flow (CBF)
      were investigated in a porcine fluid-percussion model of traumatic brain injury
      (TBI). Immature swine, under halothane anesthesia (1%), had a TBI delivered with
      a fluid-percussion device. The experimental group (n = 10) received ethanol (3.5
      gm/kg) via gastric tube followed in 1 h by TBI. Two groups of control animals
      received normal saline and TBI (n = 10) or ethanol and no TBI (n = 5). Mean
      arterial blood pressure (MAP), intracranial pressure (ICP), arterial blood gases,
      and serum lactate were monitored for 3 h after the injury. CBF was measured with
      radiolabelled 15-micron diameter microspheres. Neuropathologic changes were
      evaluated and graded after formalin perfusion and brain removal at 3 h
      postinjury. The ethanol level 60 min post-head injury was 198 +/- 70 (SD) mg/dL
      in the ethanol+TBI group. At 90 min postinjury and thereafter, ethanol+TBI
      animals compared with TBI only animals had significantly lower MAP (63 +/- 26
      mmHg vs 91 +/- 15 mmHg) and lower cerebral perfusion pressure (50 +/- 25 mmHg vs
      78 +/- 15), and at 180 min postinjury, lower CBF (87 +/- 37% vs 62 +/- 79% of
      preinjury levels). Ethanol+TBI animals had higher blood lactates (28 +/- 11 mg/dL
      vs 13 +/- 6 mg/dL) than TBI only animals. Ethanol+TBI animals also had
      significantly longer postinjury apneas (11 +/- 8 min vs 0.6 +/- 0.4 min), with
      three of ten ethanol-treated animals never recovering spontaneous respiration.
      Ethanol intoxication produced hemodynamic and respiratory changes, which may have
      a deleterious effect on outcome and mortality after brain injury.

PMID- 8258841
TI  - Alterations of protein kinase C in rat hippocampus following traumatic brain
      injury.
AB  - Calcium-dependent excitotoxic processes contribute significantly to pathologic
      responses to traumatic brain injury (TBI). TBI causes neuronal depolarization and
      excessive excitatory neurotransmitter release, which may lead to increases in
      intracellular calcium levels. However, responses of calcium-dependent enzymes
      such as protein kinase C (PKC) following TBI are poorly understood. Since PKC
      plays an important role in signal transduction and maintenance of normal neuronal
      function, we investigated changes in PKC activity and protein levels following
      fluid percussion brain injury in rats. We observed a 23.1% increase in PKC
      activity 1 h postinjury and 80.7% increase in PKC activity 3 h postinjury. There
      was no statistically significant change in PKC activity 5 min and 24 h after
      injury. PKC immunolabelling studies detected a significant increase in PKC levels
      in membrane fractions 3 h but not 1 h after injury. Thus PKC activation is
      transiently increased following TBI and may play an important role in
      pathophysiologic responses to TBI.

PMID- 8258842
TI  - Chronic corticosterone treatment potentiates deficits following traumatic brain
      injury in rats: implications for aging.
AB  - The present study examined the effect of chronic corticosterone exposure on motor
      and cognitive deficits following traumatic brain injury (TBI). Adults rats were
      treated with either corticosterone acetate (15 ug/ml) added to their drinking
      water or vehicle (0.5% alcohol) for 3 months. Following this 3-month treatment,
      corticosterone-treated rats (n = 8) and vehicle-treated rats (n = 10) were
      injured at a mild level of fluid percussion injury (1.7-1.8 atm). Additional
      corticosterone-treated (n = 8) and vehicle-treated rats (n = 8) were surgically
      prepared for injury but were not injured. Both motor (beam balance and beam
      walking) and cognitive (Morris water maze) performances were assessed following
      injury. Motor deficits were transiently enhanced following injury in rats treated
      with corticosterone. Rats treated with corticosterone were also slower in
      learning the Morris water maze than vehicle-treated rats. These findings
      demonstrate that elevated corticosterone levels potentiate the behavioral
      deficits observed after traumatic brain injury. Applied to aging research, these
      results suggest that the elevated basal levels of corticosterone present in aged
      animals may mediate the enhanced vulnerability of aged animals to traumatic brain
      injury.

PMID- 8258843
TI  - Lactated Ringer's solution alleviates brain trauma-precipitated lactic acidosis
      in hemorrhagic shock.
AB  - To determine the influence of brain trauma on blood acid-base and lactate
      pyruvate responses to hemorrhage, and the effect of lactated Ringer's solution on
      these responses, 30 anesthetized rats were assigned to four groups: hemorrhage (n
      = 7), hemorrhage following fluid percussion brain trauma (trauma-hemorrhage
      group) (n = 7), hemorrhage treated with lactated Ringer's solution (hemorrhage
      resuscitation group) (n = 8), and hemorrhage following brain trauma treated with
      lactated Ringer's solution (trauma-hemorrhage-resuscitation group) (n = 8). The
      hemorrhage group showed no significant changes in pH, HCO3, and base excess after
      hemorrhage. Base excess and pH were significantly reduced after the hemorrhage in
      the trauma-hemorrhage group but were raised after resuscitation in the hemorrhage
      resuscitation group. Acid-base values showed no difference between the trauma
      hemorrhage-resuscitation and hemorrhage groups. The trauma-hemorrhage
      resuscitation group also had a significantly higher base excess than the trauma
      hemorrhage group. Lactate rose significantly after hemorrhage in the hemorrhage
      group and was even higher in the trauma-hemorrhage group, but there were no
      differences between the hemorrhage versus hemorrhage-resuscitation or trauma
      hemorrhage-resuscitation groups. Both brain trauma and lactated Ringer's solution
      increased pyruvate with marked reduction in the ratio of lactate to pyruvate.
      These data indicate that brain trauma precipitates blood lactate accumulation and
      metabolic acidosis after hemorrhage, and infusion of lactated Ringer's solution
      can relieve these disturbances.

PMID- 8258844
TI  - Surface and epidural lumbosacral spinal cord evoked potentials in chronic spinal
      cord injury.
AB  - Nine patients were examined in the chronic stage of spinal cord injury (12 to 56
      months postinjury). Surface lumbosacral spinal cord evoked potentials (LSEPs)
      were obtained using electrodes placed over the S1, L2, L4, and T12 vertebral
      levels, referenced to a T6 surface electrode. Epidural LSEPs were obtained using
      a multielectrode lead placed percutaneously into the epidural space for
      evaluation of the efficacy of spinal cord stimulation for modification of pain
      and spasticity. The LSEPs resulting from supramaximal stimulation of the tibial
      nerve at the popliteal fossa were composed of propagating and stationary action
      potential components. Based on the surface LSEP amplitudes and latencies
      established in healthy subjects, the data was divided into normal (less than 2
      SD), marginal (between 2 and 2.5 SD), and abnormal (greater than 2.5 SD)
      categories. Comparison of surface and epidural LSEPs at the T12 vertebral level
      for the normal group (n = 6, 4 incomplete and 2 complete) revealed a mean
      epidural/surface amplitude ratio of 9.44 and a latency for the major negative
      component of 15.2 +/- 0.6 ms for the epidural versus 14.8 +/- 0.6 ms for the
      surface LSEP. In cases where the lead was progressively removed and LSEPs
      recorded (n = 4) the propagating components rapidly attenuated and increased in
      duration while the stationary components attenuated but did not change in
      duration. The LSEPs for the marginal group (n = 2, 1 incomplete and 1 complete)
      showed similar epidural/surface amplitude ratios. In the abnormal case (n = 1,
      complete) surface LSEPs were absent but epidural LSEPs were present but with
      stationary and propagating components of low amplitude. This study demonstrates
      the ability of the epidural LSEP to provide more information than the surface
      LSEP of the functional condition of the lumbosacral spinal cord, particularly
      regarding the character of the propagating action potentials and in cases when
      the surface LSEPs appear to be of very low amplitude or absent.

PMID- 8258845
TI  - Myoelectric evoked potentials versus locomotor recovery in chronic spinal cord
      injured rats.
AB  - The purpose of this study was to determine the utility of descending evoked
      potentials in evaluating functional recovery in rats after spinal cord contusion
      injury. Rats received thoracic contusions at T9 using a controlled-displacement
      impactor. They were evaluated for 5 weeks postinjury using auditory startle
      responses (ASR) while alert, or by cerebellar motor evoked potentials (CMEP)
      while anesthetized. ASR and CMEP were recorded electromyographically from
      forelimb and hindlimb muscles. Open field locomotor performance was also assessed
      and recovered to almost normal levels by 3 weeks postinjury. Histologic analysis
      of the injury site indicated that the contusions destroyed approximately 70% of
      the cross-sectional area of the cord. Although the remaining 30% was sufficient
      to preserve nearly normal locomotor behavior, ASR and CMEP amplitudes in hindlimb
      flexors and extensors were reduced by 90% or more after injury and showed
      virtually no recovery. Significant ASR and CMEP responses were present in the
      cutaneous trunk muscles of the lower torso after injury. These muscles are
      innervated via peripheral nerves originating at cord levels above the injury.
      Multi-wave field potentials normally recorded from the dorsal cord surface in
      response to cerebellar stimulation were absent in injured rats, suggesting
      minimal if any activation of segmental neurons via the pathways normally
      mediating CMEP. The tracts mediating ASR and CMEP thus appear to be highly
      sensitive to mild spinal cord trauma but are evidently not essential for support
      or walking.

PMID- 8258846
TI  - An experimental model combining microdialysis with electrophysiology, histology,
      and neurochemistry for exploring mechanisms of secondary damage in spinal cord
      injury: effects of potassium.
AB  - An experimental model for characterizing effects of agents suspected to cause
      damage secondary to spinal cord injury is presented. Microdialysis was used to
      administer candidate damaging agents and to sample the release of other
      substances in response to administered agents. Damage was assessed by monitoring
      the amplitudes of evoked potentials during candidate administration and by
      postmortem histologic examination. This approach enabled the correlation of
      electrophysiologic, histologic, and neurochemical parameters in the same
      experiment. Potassium was chosen as a candidate damaging agent, because (1) in
      high extracellular concentrations it destroys neurons and (2) its extracellular
      concentration rises substantially following impact injury to the spinal cord. A
      technique using parallel administering and collecting microdialysis fibers was
      developed to estimate the in vivo concentration of K+ outside the administering
      fiber. Administration of 100 mM KCl, 50 mM K2HPO4, or 100 mM potassium
      glucuronate in artificial cerebrospinal fluid blocked electrical conduction and
      destroyed cell bodies. Release of the neurotransmitter amino acids aspartate,
      glutamate, glycine, and gamma-aminobutyric acid (GABA) and the possible
      neurotransmitter taurine were dramatically increased by administration of 100 mM
      KCl. Levels of non-neurotransmitter amino acids increased to lesser degrees.
      Impairment of conduction, destruction of cell bodies, and release of excitotoxins
      were all consistent with elevated K+ serving as a secondary damaging agent in
      spinal cord injury.

PMID- 8258847
TI  - Mutagenic and clastogenic properties of (3-[3-(6-benzoyloxy-3-cyano-2-
      pyridyloxycarbonyl) benzoyl]-1-ethoxymethyl-5-fluorouracil) (BOF-A2), a new 5
      fluorouracil derivative with anti-tumour activity.
AB  - As part of the safety assessment of (3-[3-(6-benzoyloxy-3-cyano-2-
      pyridyloxycarbonyl)benzoyl]-1-ethoxymethyl-5-fluorouracil) (BOF-A2), a new 5
      fluorouracil (5-FU) derivative with anti-tumour activity, its potential
      genotoxicity was studied in 3 different tests. BOF-A2 was negative in a reverse
      mutation (Ames) test in strains of S. typhimurium and E. coli. BOF-A2 induced
      chromosomal aberrations in Chinese hamster cells in vitro especially in the
      presence of exogenous metabolic activation, and was clastogenic in vivo, inducing
      micronuclei in mouse bone marrow. The clastogenic activity of BOF-A2 was similar
      to that of 5-FU.

PMID- 8258848
TI  - Effect of intravenous inoculation of avian influenza virus on reproduction and
      growth in mallard ducks.
AB  - An avian influenza virus isolate, A/Mallard/Ohio/184/86 (H5N1), was evaluated for
      its effects on reproduction in isolation-reared adult mallard ducks (Anas
      platyrhynchos) and growth rate in juvenile mallards after intravenous
      inoculation. There was a significant decrease in egg production in the
      experimental group during the first week after inoculation, but it returned to
      the normal production level during the second week. No effect was seen on egg
      weight, shape, or fertility. Ducklings receiving this influenza virus isolate did
      not differ from controls in their rate of growth.

PMID- 8258849
TI  - Experimental infection of the eastern chipmunk (Tamias striatus) with the Lyme
      disease spirochete (Borrelia burgdorferi).
AB  - Lyme disease, caused by the spirochete Borrelia burgdorferi, is endemic in the
      northeast, north-central, and Pacific coastal states of the United States. The
      eastern chipmunk (Tamias striatus) is found throughout the disease-enzootic
      regions except along the Pacific coast, and may serve as an important reservoir
      host in some locations. To characterize their potential as a host, 11 adult
      chipmunks were inoculated with 10(5) spirochetes from strains of B. burgdorferi
      isolated from Peromyscus leucopus and Ixodes scapularis in a hyperendemic area of
      Westchester County, New York (USA). All inoculated chipmunks became infected.
      Spirochetemias were detected by isolating spirochetes in Barbour-Stoenner-Kelly
      media in eight of eight chipmunks, and lasted for 2 to 5 days. Spirochetes were
      isolated from the ears of all animals, starting at 1 wk and for < or = 4 mo, and
      from various internal organs at 133 days post-inoculation. Laboratory-reared
      larval I. scapularis ticks became infected with spirochetes after feeding on two
      of the inoculated chipmunks.

PMID- 8258850
TI  - Seasonal prevalence of Clostridium botulinum type C in sediments of a northern
      California wetland.
AB  - The prevalence of Clostridium botulinum type C (% of positive sediment samples)
      was determined in 10 marshes at Sacramento National Wildlife Refuge (SNWR),
      located in the Central Valley of California (USA), where avian botulism
      epizootics occur regularly. Fifty-two percent of 2,200 sediment samples collected
      over an 18-mo period contained C. botulinum type C (both neurotoxic and
      aneurotoxic) which was present throughout the year in all 10 marshes. The
      prevalence of C. botulinum type C was similar in marshes with either high or low
      botulism losses in the previous 5 yr. Marshes with avian botulism mortality
      during the study had similar prevalences as marshes with no mortality. However,
      the prevalence of C. botulinum type C was higher in marshes that remained flooded
      all year (permanent) compared with marshes that were drained in the spring and
      reflooded in the fall (seasonal). The prevalence of C. botulinum type C declined
      in seasonal marshes during the dry period. Similar declines did not occur in the
      permanently flooded marshes.

PMID- 8258852
TI  - A retrospective serologic survey for Anaplasma spp. infection in three bighorn
      sheep (Ovis canadensis) populations in California.
AB  - Using an indirect immunofluorescence assay, we determined the prevalence of
      Anaplasma-reactive antibody in three herds of bighorn sheep, each a different
      subspecies and occupying a different habitat in California (USA). Antibodies to
      Anaplasma spp. were identified in none of twenty California bighorn (Ovis
      canadensis californiana) sampled from the Mt. Baxter herd, 11 of 17 peninsular
      bighorn (O. canadensis cremnobates) sampled in the Santa Rosa Mountains, and all
      20 desert bighorn (O. canadensis nelsoni) sampled at Old Dad Peak/Kelso
      Mountains. Based on an assay and an adsorption technique, the titers most likely
      were due to Anaplasma ovis. The presence and species of tick vectors in each of
      the habitats, and the presence or absence of deer or livestock were identified as
      factors potentially influencing seroprevalence of antibodies.

PMID- 8258851
TI  - Characterization of an Anaplasma ovis isolate from desert bighorn sheep in
      southern California.
AB  - To understand the role of bighorn sheep (Ovis canadensis) in the epidemiology of
      anaplasmosis, we recovered a field isolate from a suspected enzootic area in
      southern California (USA). Whole blood was collected from three desert bighorn
      sheep (Ovis canadensis nelsoni) and inoculated into a susceptible splenectomized
      domestic sheep, calf and a susceptible spleen-intact bighorn sheep. No infection
      occurred in the calf, but a detectable infection developed in both the domestic
      sheep and bighorn sheep 24 days after inoculation. The infection in both domestic
      and bighorn sheep resulted in severe clinical disease but was resolved with the
      use of tetracycline. Using monoclonal antibodies and DNA probes, we confirmed
      that the isolate was Anaplasma ovis.

PMID- 8258853
TI  - Blood parasites in birds from Monteverde, Costa Rica.
AB  - In a survey of avian blood parasites in Costa Rica, 51 (11%) of 479 birds sampled
      were infected by at least one species of hematozoan. Fourteen of the 60 species
      of birds in the survey were examined for the first time. Infections were most
      common in ramphastids and emberizids and infrequent in other taxa. Among resident
      species, infections were more commonly detected during the wet season when most
      birds breed than during the dry season when few birds breed. Infections caused by
      Haemoproteus sp. were most common, while Plasmodium sp., Leucocytozoon sp.,
      Trypanosoma sp., and microfilarial infections were rare. The intensity of the 40
      Haemoproteus infections in adult birds was low, with a mean +/- SE of 12.5 +/-
      3.7 infected cells per 10,000. Haemoproteus infections did not undergo seasonal
      changes in intensity.

PMID- 8258854
TI  - Prevalence of Leptospira antibodies in white-tailed deer, Cades Cove, Great Smoky
      Mountains National Park, Tennessee, USA.
AB  - We conducted a study of the population dynamics, movement, and diseases of white
      tailed deer (Odocoileus virginianus) in Cades Cove, Great Smoky Mountains
      National Park, Tennessee (USA) from 1980 to 1984. During the study 590 blood
      samples were collected from 518 deer, with some deer recaptured one or two times.
      The estimated percent of the herd sampled each year ranged from 8% to 28%. We
      also collected serum samples from 56 cattle pastured in Cades Cove. Deer and
      cattle sera were tested using the microagglutination test for the presence of
      antibody to the following serovars of Leptospira: pomona, hardjo, grippotyphosa,
      icterohemorrhagiae, and canicola. One hundred and six deer (21%) were
      seropositive for only one of the serovars. We found that 57 (11%) of the deer had
      antibodies to serovar hardjo, 33 (6%) were positive for antibodies to serovar
      pomona, 15 (3%) were positive for antibodies to serovar icterohemorrhagiae, and
      one deer had antibodies to serovar canicola. Age class and sex of deer were
      associated with antibody presence. Adult (> or = 1.5 yr) male deer were more
      likely to have antibodies than the other age class and sex groups (P = 0.001). In
      recaptured deer, similar titers were found in samples from one deer taken 807
      days apart. Titer declined below the screening dilution level (1:250) after 37
      days in one deer.

PMID- 8258855
TI  - Evidence of ortho- and paramyxoviruses in fauna from Antarctica.
AB  - Serum antibodies to influenza A viruses and paramyxoviruses were detected in
      Adelie penguin (Pysoscelis adeliae) and Antarctic skua (Stercorarius skua
      maccormicki) sera in the Ross Sea Dependency. An avian paramyxovirus was isolated
      from a penguin cloacal swab.

PMID- 8258856
TI  - Serologic survey for selected viral and rickettsial agents of brown bears (Ursus
      arctos) in Croatia.
AB  - Sera from 22 (13 wild and nine captive) European brown bears (Ursus arctos) from
      Croatia were tested to 18 viral and rickettsial agents. Serologic evidence of
      exposure was found to the following agents (number positive/number examined):
      Bhanja virus (3/15), Tahyna virus (3/15), West Nile virus (4/15), Naples sandfly
      fever virus (1/15), human adenovirus (1/22), influenza A (1/22) and B (1/22)
      virus, cytomegalovirus (1/22), parainfluenza virus 1 (2/22), Chlamydia psittaci
      (1/22), Coxiella burnetii (2/22), and canine parvovirus 2 (CPV-2) (7/22).
      Evidence of exposure to arboviruses was found exclusively among free-living
      bears. Evidence of exposure to agents usually transmitted directly was
      predominant among captive bears. Canine parvovirus 2 antibodies were the most
      frequently found antibodies and the only antibody common to both groups of bears.
      This may be the first report of antibodies to CPV-2 in bears.

PMID- 8258857
TI  - Blood lead concentrations of waterfowl from unhunted and heavily hunted marshes
      of Nova Scotia and Prince Edward Island, Canada.
AB  - Blood lead concentrations of juvenile American black ducks (Anas rubripes)
      sampled in unhunted sanctuaries of Nova Scotia (NS) and Prince Edward Island
      (PEI), Canada, usually were < 30 parts per billion (ppb). Based on gizzard
      content analyses of juvenile American black ducks from hunted areas, eight (24%)
      of 33 flightless birds contained ingested lead shot. Blood lead concentrations
      were > or = 100 ppb in seven of eight juveniles with ingested shot; thus we
      adopted blood lead concentrations 100 ppb as our threshold indicating exposure to
      non-background lead. The proportion of both American black ducks and ring-necked
      ducks (Aythya collaris) with elevated blood lead concentrations (> 100 ppb)
      exceeded 5% in hunted areas sampled in NS and PEI combined. The Canadian Wildlife
      Service draft policy is to consider replacing lead shot with non-toxic shot for
      waterfowl and snipe hunting if 5% of American black ducks exceed a blood lead
      concentration of 200 ppb. American black ducks significantly (P < 0.05) exceeded
      this threshold but ring-necked ducks did not. The source of lead in hunted areas
      may have been lead shot; we recommend that it be eliminated and replaced by an
      acceptable non-toxic shot for waterfowl hunting. Twenty four (96%) of 25 of
      American black ducks overwintering in Sullivans Pond, Dartmouth, NS, contained
      elevated (> 100 ppb) blood lead concentrations and 19 (76%) had detrimental
      concentrations (> 200 ppb). We believe that the source of lead at Sullivans Pond
      was automobile emissions.

PMID- 8258858
TI  - Lead concentrations in liver and kidneys of snow geese during an avian cholera
      epizootic in California.
AB  - During an avian cholera epornitic, between December 1982 and January 1983, 58
      dead, 23 sick, and 106 hunter-killed lesser snow geese (Chen caerulescens
      caerulescens) were collected at Delevan National Wildlife Refuge, Colusa County,
      California, USA. Fifty-one of the dead and sick geese were infected with
      Pasteurella multocida. Lead concentrations in the livers ranged from < 1 to 253
      parts per million (ppm) (dry weight). Lead concentrations in the kidneys ranged
      from < 1 ppm to 547 ppm (dry weight). Snow geese with > 30 ppm lead, considered
      diagnostic of acute lead poisoning, had significantly (P < 0.05) lower heart
      weights and a smaller band of heart fat, compared to geese with tissue lead
      concentrations of < 30 ppm. Tissue lead concentrations in geese dying from avian
      cholera generally were lower than concentrations in hunter-killed geese, but the
      differences were not significant for either kidney (P = 0.08) or liver (P = 0.30)
      tissue.

PMID- 8258859
TI  - Mycotic gastritis of juvenile ayu (Plecoglossus altivelis) caused by Saprolegnia
      diclina type 1.
AB  - Histopathological and mycological studies were made on mycotic gastritis in
      juvenile ayu, Plecoglossus altivelis. The disease occurred 5 days after the
      transportation of fish from a hatchery pond to two rearing ponds of Tochigi
      Prefectural Fisheries Experiment Station, Tochigi, Japan. The pyloric region of
      the stomach was red. Numerous fungal hyphae penetrated into the stomach wall.
      Seven fungal isolates were obtained from the lesions. Three isolates were
      identified as Saprolegnia diclina Type 1. Based on histology, hyphae were most
      numerous in the pyloric stomach, but also penetrated abdominal adipose tissue,
      the pancreas, spleen, kidney, swim bladder, gonad, and liver. In some cases, the
      hyphae penetrated trunk muscles.

PMID- 8258860
TI  - Mixed infection of an acid-fast bacterium and an imperfect fungus in a Napoleon
      fish (Cheilinus undulatus).
AB  - A Napoleon fish (Cheilinus undulatus) was infected with both an acid-fast
      bacterium and an imperfect fungus. This is the first report of an acid-fast
      bacterial infection in Cheilinus undulatus, and the first observation of an
      imperfect fungus in the swim bladder of a tropical marine fish.

PMID- 8258861
TI  - Naturally occurring Brucella suis biovar 4 infection in a moose (Alces alces).
AB  - A debilitated adult female moose (Alces alces) shot east of the MacKenzie River,
      Northwest Territories, Canada, had large fluctuant masses over both carpi. Only
      the forelimbs were available for examination. Carpal pathology included bilateral
      bursitis and osteomyelitis of subjacent bone. In addition severe osteomyelitis
      with fractures was observed in the left lateral and right medial digits. Brucella
      suis biovar 4 was isolated from the right medial first phalanx. This is believed
      to be the first reported case of infection with this organism in a wild moose.
      The bacterium is common in caribou (Rangifer tarandus) in the region.

PMID- 8258862
TI  - Prevalence of Toxoplasma gondii infections in Pennsylvania black bears, Ursus
      americanus.
AB  - Serum samples from 665 hunter-killed black bears killed in 1989 to 1992
      throughout Pennsylvania (USA) were tested for Toxoplasma gondii antibodies by the
      agglutination test in dilutions of 1:25, 1:50, and 1:500. Toxoplasma gondii
      antibodies were found in 535 of 665 (80%) bears. Considering the highest
      dilutions at which antibodies were detected, prevalences were 10% at 1:25, 37% at
      1:50 and 33% at 1:500. No significant difference in antibody prevalence was found
      between males (79%) and females (80%), but a significant difference was found
      between juvenile (65%) and adult (83%) bears.

PMID- 8258863
TI  - Leptospirosis serology in Korean wild animals.
AB  - A study was undertaken on wild animals to determine the seroprevalence of animal
      leptospirosis in Korea. Using the serum microagglutination test for 19
      serogroups, it was shown that two of 26 rats (Rattus rattus) had antibodies to
      Leptospira canicola. When data for domestic animals were included, the most
      prevalent (nearly 50%) serogroup was Leptospira canicola.

PMID- 8258864
TI  - A serologic survey for some bacterial and viral zoonoses in game animals in the
      Czech Republic.
AB  - Between 1986 and 1991, sera were collected from 33 roe deer (Capreolus
      capreolus), 24 red deer (Cervus elaphus), four fallow deer (Dama dama), two
      mouflon (Ovis musimon), 34 wild boars (Sus scrofa), and 48 hares (Lepus
      europaeus) shot in two areas of the Czech Republic. Collectively, the sera
      contained antibodies to Coxiella burnetii (prevalence of 12%), Francisella
      tularensis (4%), Brucella spp. (2%), Central European tick-borne encephalitis
      virus (8%), Tahyna (California serogroup) virus (36%), and Calovo (= Batai) virus
      (23%). We propose that these mammals may play a role in maintaining natural foci
      of Q-fever, Tahyna fever and Calovo virus infection.

PMID- 8258866
TI  - Traumatic injuries occurring in possums and gliders in the Blue Mountains, New
      South Wales.
AB  - Twenty common brushtail possums (Trichosurus vulpecula), 23 ringtail possums
      (Pseudocheirus peregrinus) and five sugar gliders (Petaurus breviceps) from the
      Blue Mountains, New South Wales, Australia were evaluated for traumatic injuries
      between 1989 and 1990. Ten brushtail possums and five ringtail possums were hit
      by motor vehicles with injuries primarily to the anterior of the body. Fifteen
      ringtail possums and all sugar gliders were attacked by cats. Four brushtail
      possums were attacked by dogs. The remaining nine possums had evidence of
      intraspecific fighting (n = 2) or other types of trauma. Brushtail and ringtail
      possums were presented primarily during their main breeding seasons. There was no
      sex predilection. More ringtail than brushtail possums were subadults and these
      were injured primarily at the time of dispersal.

PMID- 8258865
TI  - Serologic survey for leptospirae in European brown bears (Ursus arctos) in
      Croatia.
AB  - From 1981 to 1991, sera of 42 European brown bears (Ursus arctos) from three
      areas in Croatia were tested for antibodies against 12 Leptospira interrogans
      serovars: grippotyphosa, sejroe, australis, pomona, canicola,
      icterohaemorrhagiae, tarassovi, saxkoebing, ballum, bataviae, poi, and hardjo.
      Diagnostic levels of antibody were found in 17 (40%) of 42 sera. Evidence of
      exposure to at least one of the serovars was found in seven of 14 free-ranging
      bears from the Lika region, four of 12 free-ranging bears from the Gorski Kotar
      region, zero of six orphaned cubs from the Gorski Kotar region, and six of 10
      captive bears from the Zagreb Zoo. Based on the antibody titers, we implicated
      the following serovars: australis in five bears, sejroe in two bears, canicola in
      one bear, and icterohaemorrhagiae in one bear. There was a strong correlation
      between serovars implicated by this survey and serovars previously isolated from
      small mammals in Croatia.

PMID- 8258867
TI  - Squamous cell carcinoma of the skin in a Pere David's deer (Elaphurus
      davidianus).
AB  - A solitary mass overlying the right carpal joint region's skin in an 18-year-old
      female Pere David's deer (Elaphurus davidianus) was surgically excised and
      histologically diagnosed as a squamous cell carcinoma (SCC). The tumor was
      locally infiltrative, showing rather few "horn pearls" and many mitotic figures.
      This is the first report of a cutaneous SCC in the Pere David's deer.

PMID- 8258868
TI  - Syndactylism and brachygnathia in a white-tailed deer.
AB  - A white-tailed deer (Odocoileus virginianus) fawn was presented to the
      Southeastern Cooperative Wildlife Disease Study for examination of brachygnathia
      and syndactylous front feet. The hoof keratin of digits 3 and 4 was completely
      fused and typical sole integument covered the palmar surface between the primary
      digits. Based on a radiographic examination, there was fusion of the epiphyses of
      the first phalanges of digits 3 and 4 in both feet. In the right foot the
      proximal metaphyses of the first phalanges of digits 3 and 4 were fused.

PMID- 8258869
TI  - Retrospective study of diseases in a captive Lemming Colony.
AB  - Fifty-four ill or nonproductive lemmings (Dicrostonyx spp.) were evaluated for
      signs, lesions and causes of disease for 5 yr in a domestic colony. Parasitic
      granulomas caused by Encephalitozoon cuniculi were the most common finding and
      were seen in 22 lemmings. The disease was characterized by circling and
      torticollis with granulomas in many tissues, especially the central nervous
      system. Suppurative otitis occurred in 12 lemmings and was associated with
      Klebsiella pneumonia infection; circling was the common sign. Hepatic
      microabscesses were present in seven lemmings but a cause was not identified.
      Five lemmings had neoplasms and 14 had either suppurative processes, aspermia, or
      ovarian cysts.

PMID- 8258871
TI  - Pharmaceutical firms urge more patient education.

PMID- 8258870
TI  - 'Icebreaker' clears way for gun control efforts.

PMID- 8258872
TI  - From the National Institutes of Health.

PMID- 8258874
TI  - From the Centers for Disease Control and Prevention. Absence of reported measles-
      United States, November 1993.

PMID- 8258873
TI  - From the Centers for Disease Control and Prevention. Infant mortality--United
      States, 1991.

PMID- 8258875
TI  - A piece of my mind. Laphroaig.

PMID- 8258876
TI  - Assisted suicide: sheer cliff or clinical reality?

PMID- 8258877
TI  - Assisted suicide: sheer cliff or clinical reality?

PMID- 8258878
TI  - The diagnostic value of the forced expiratory time.

PMID- 8258879
TI  - The diagnostic value of the forced expiratory time.

PMID- 8258880
TI  - Ankle/arm blood pressure index.

PMID- 8258881
TI  - Ankle/arm blood pressure index.

PMID- 8258882
TI  - Pentoxifylline in the treatment of children with new-onset type I diabetes
      mellitus.

PMID- 8258883
TI  - Dismal rehabilitation in geriatric inner-city hemodialysis patients.
AB  - OBJECTIVE: To assess the extent of functional and vocational rehabilitation
      achieved by elderly inner-city patients sustained on maintenance hemodialysis.
      DESIGN: Inception cohort study of elderly patients who have end-stage renal
      disease using a modified Karnofsky rating system. The need for a wheelchair,
      participation in household activities, and effect of comorbid conditions were
      noted. Current status was compared with patient's recollection of functional
      activity level 2 years before commencing maintenance hemodialysis. SETTING: Seven
      outpatient, hospital-affiliated and private hemodialysis units in Brooklyn, NY.
      PATIENTS: One hundred four patients aged 65 years or older who were receiving
      maintenance hemodialysis for at least 6 months. MAIN OUTCOME MEASURES: A score of
      76 or greater on a modified Karnofsky scale indicated independent function at a
      level that permitted participation in activities beyond those mandated by the
      hemodialysis regimen. A comorbidity score 6 or greater on a newly constructed
      index correlated with severe debility. Employment status was also recorded.
      RESULTS: Present functional activity had deteriorated to a modified Karnofsky
      score of 66 +/- 12.3 (+/- SD) compared with patients' recollection of a mean
      score of 84 +/- 14.3 (P < .001) 2 years before initiation of hemodialysis.
      Diabetic patients had a lower score than nondiabetic patients. The mean
      comorbidity index of the entire study group was 7.8 +/- 2.9 (mean +/- SD). Within
      the diabetic subset, severe debility constrained 71 patients (68%) to limit all
      activity to their residence with the exception of travel to and from their
      dialysis facility. By contrast, 2 years prior to commencing dialytic therapy, 81
      diabetic patients (78%) had interests and activities that took them outside their
      homes (P < .001). Generalized weakness was the most common explanation given for
      the lack of outside activity by nine patients (9%) who were wheelchair bound.
      Erythropoietin, though regularly administered to 87 patients (84%) in the study
      group, was unsuccessful in raising mean hematocrit reading above 0.28 +/- 0.05
      (mean +/- SD). CONCLUSIONS: Maintenance hemodialysis does not return inner-city
      elderly patients to their predialysis level of functioning. Few elderly, diabetic
      hemodialysis patients conduct any substantive portion of their lives outside
      their homes. For nondiabetic patients, the modified Karnofsky score of whites
      (70.4 +/- 11.9) and blacks (66.5 +/- 15.3), though low, was equivalent (P < .4).

PMID- 8258884
TI  - Effect of age and diagnosis on survival of older patients beginning chronic
      dialysis.
AB  - OBJECTIVE: To assess the survival of elderly patients in the United States
      beginning chronic dialysis for end-stage renal disease caused by diabetes
      mellitus, hypertension, glomerulonephritis, polycystic kidney disease, and other
      causes. DESIGN: A secondary analysis of data obtained from the Health Care
      Financing Administration. PATIENTS: All Medicare end-stage renal disease patients
      55 years of age or older (n = 95,394) who began chronic dialysis treatment in the
      US between 1982 and 1987. MAIN OUTCOME MEASURES: The 1-, 3-, and 5-year survival
      rates for each of six age strata and, within each strata, for each of the four
      most frequent causes of renal failure. RESULTS: Survival rates of dialysis
      patients fell precipitously, and much more rapidly for the study group than for
      the general population, as a function of advancing age. Older patients with
      diabetic nephropathy fared particularly badly, such that no patients with
      diabetic nephropathy aged 85 years or more survived 5 years. CONCLUSIONS:
      Mortality rates of patients older than 55 years beginning chronic dialysis
      treatment increased dramatically as age at initiation of dialysis increased.
      Clinically meaningful survival data should prove useful to persons making
      decisions about the initiation of chronic dialysis.

PMID- 8258885
TI  - HIV-specific T-helper activity in seronegative health care workers exposed to
      contaminated blood.
AB  - OBJECTIVE: To evaluate human immunodeficiency virus (HIV) type 1-specific
      cellular immune responses in HIV-seronegative health care workers with
      occupational high-risk exposures to HIV-infected (HIV-positive) patients. DESIGN:
      Peripheral blood mononuclear cells (PBMCs) were obtained after occupational
      exposures to HIV, and PBMCs from health care workers exposed to HIV-negative
      patients served as controls. The PBMCs were stimulated in vitro with HIV envelope
      synthetic peptides. Interleukin 2 (IL-2) production was measured in a bioassay.
      The HIV antibody status was determined by standard enzyme-linked immunosorbent
      assays. Exposed individuals were also evaluated for HIV proviral DNA by
      polymerase chain reaction techniques. PARTICIPANTS: The PBMCs from eight health
      care workers with high-risk exposures and nine control health care workers were
      studied. RESULTS: The PBMCs from all individuals showed strong IL-2 production to
      control antigens, indicating intact T-helper function. Interleukin 2 production
      to HIV peptides was detected in PBMCs from six of eight HIV-exposed individuals,
      but in only one of the nine health care workers exposed to HIV-negative body
      fluids (P < .008). None of the HIV-exposed health care workers became infected as
      determined by negative HIV antibody and polymerase chain reaction analysis after
      follow-up evaluation that ranged from 8 to 64 weeks. CONCLUSION: Human
      immunodeficiency virus-specific T-helper activity was detected in six (75%) of
      eight HIV-negative health care workers with exposure to HIV-positive body fluids.
      Potent HIV-specific T-helper activity was detectable 4 to 8 weeks after the
      exposure and was lost in individuals followed up for 8 to 64 weeks. Three health
      care workers remained responsive at 8, 19, and 24 weeks. Exposure to HIV without
      evidence of subsequent infection appears to result in activation of cellular
      immunity without activation of antibody production.

PMID- 8258886
TI  - Gene therapy and the hemophilias.
AB  - Gene therapy for hemophilia A and B, now in the developmental stage, holds
      promise of a therapeutic revolution, resulting in amelioration or cure of the
      hemorrhagic diatheses. The genes for factor VIII and IX have been cloned, and
      vectors for the transfer of their cDNA into cells have been developed. Although
      viral and nonviral constructs containing the hemophilia gene have been used, most
      often modified retroviruses or adenoviruses have been employed. Cells that have
      been targeted for genetic modification to produce the antihemophilic proteins
      include hepatocytes, muscle cells, endothelial cells, keratinocytes, and
      fibroblasts. The delivery system may be (1) ex vivo, with implantation of
      modified cultured hemophilic cells in the donor, either in tissues or in
      semipermeable capsules, or (2) in vivo, the vector being delivered directly to
      target cells, genetically modifying them in situ. Successful in vivo therapy has
      been demonstrated in a hemophilic animal model, with conversion to a less severe
      hemophilic state.

PMID- 8258887
TI  - New holographic process provides noninvasive, 3-D anatomic views.

PMID- 8258888
TI  - Carbon monoxide poisoning from indoor burning of charcoal briquets.
AB  - OBJECTIVE: To describe the case characteristics of a series of patients poisoned
      with carbon monoxide (CO) resulting from indoor burning of charcoal briquets.
      DESIGN: Cases of patients with unintentional CO poisoning referred for treatment
      with hyperbaric oxygen were reviewed. Cases that occurred as the result of indoor
      burning of charcoal briquets were analyzed. SETTING: A private, urban, tertiary
      care center. PATIENTS: Seventy-nine patients ranging from 3 months to 87 years of
      age referred from 10 counties within the state of Washington between October 1982
      and October 1993. RESULTS: Of 509 patients treated for acute unintentional CO
      poisoning, 79 cases occurred in 32 incidents as a result of indoor burning of
      charcoal briquets, for the purpose of either home heating or cooking. A majority
      of cases occurred in the months of October through January, commonly during power
      outages or when electricity was intentionally disconnected. Patients of minority
      races were disproportionately represented compared with the general population of
      the region. CONCLUSIONS: Carbon monoxide poisoning is a significant hazard from
      indoor use of charcoal briquets. All cases are avoidable and public awareness of
      the risk should be enhanced.

PMID- 8258889
TI  - The rational clinical examination. Is this patient malnourished?

PMID- 8258890
TI  - Users' guides to the medical literature. II. How to use an article about therapy
      or prevention. B. What were the results and will they help me in caring for my
      patients? Evidence-Based Medicine Working Group.

PMID- 8258891
TI  - Dynamics of people without health insurance. Don't let the numbers fool you.

PMID- 8258892
TI  - Dialysis, old age, and rehabilitation.

PMID- 8258893
TI  - Pertussis vaccines. A progress report.

PMID- 8258894
TI  - A renewed relationship.

PMID- 8258895
TI  - Enhancing patient adherence to medical recommendations.

PMID- 8258896
TI  - Foodborne illness problems more than enteric.

PMID- 8258897
TI  - Strategies for enhancing patient adherence to medical recommendations.

PMID- 8258898
TI  - Contingency contracting for improving adherence in pediatric populations.

PMID- 8258899
TI  - To live a normal life: history and health behavior.

PMID- 8258900
TI  - Determination of some butyrophenones in body fluids by gas chromatography with
      surface ionization detection.
AB  - Haloperidol, moperone, pipamperone and bromperidol were found measurable with
      high sensitivity by gas chromatography (GC) with surface ionization detection
      (SID). The calibration curves using moperone as internal standard were linear in
      the range of 0.4-4 pmol on column for haloperidol, pipamperone, and bromperidol.
      The detection limit of the drugs was about 0.1 pmol on column. For their actual
      determination with forensic samples, a detailed procedure for their extraction
      from human whole blood and urine was established with Sep-Pak C18 cartridges. The
      recovery of the 4 drugs, which had been added to whole blood and urine, was more
      than 90%. Haloperidol in whole blood and urine of a schizophrenic patient, who
      had been administered with this drug (3 mg/day p.o.), could be quantitated by the
      present GC-SID, and the levels were 7.18 and 43.2 pmol/ml, respectively.

PMID- 8258901
TI  - [Forensic toxicological application of TOXI-LAB screening for biological
      specimens in autopsy cases and emergency cares].
AB  - Using the TOXI-LAB drug detection system, emergency toxicological screening was
      performed in autopsy cases and emergency cares. In 280 autopsy cases (male 182
      cases 65%, female 98 cases 35%), drug positive cases were 28 cases of male (15%)
      and 24 cases of female (24%). The age groups which showed higher rate of drug
      positive cases were 10s-40s in male (approximately 20%) and 20s in female (67%).
      In the 238 cases of emergency care (male 129 cases 54%, female 104 cases 44%,
      unknown 5 cases 2%), drugs were positive in 29 cases of male (22%) and 32 cases
      of female (30%). The age groups which showed relatively higher rate of drug
      positive cases were 40s in male (64%), 20s (71%) and 30s (89%) in female. Forty
      four different kinds of drugs were detected in TOXI-LAB positive cases, in which
      the psychotropic drugs and the sedative-hypnotic drugs amounted to approximately
      70%. Methamphetamine and amphetamine, which were the main abused drugs showing a
      socially important problem, were detected in total 15 cases. TOXI-LAB was based
      on thin-layer chromatography (TLC); however, from the extraction to development,
      coloration and detection have been accelerated (about 50 min) and simplified. In
      order to perform the forensic toxicological practice in Japan, it becomes more
      useful that TOXI-LAB is used in autopsy cases and emergency cares, if the drugs,
      which have caused poisoning cares in Japan, are added to TOXI-LAB. The present
      study describes the advantage and problem of TOXI-LAB drug detection system
      through demonstrating the practical cases of autopsy cases and emergency cares.

PMID- 8258902
TI  - [DNA typing of the three HLA-class II loci from saliva stains].
AB  - The DNA typing of the HLA-class II loci, HLA-DPB1, HLA-DQA1 and HLA-DRB, from
      saliva stains is described. In addition to the experimentally prepared saliva
      stains, a stain on a towel in a burglar case was subjected to the analysis. Using
      10 ng of the extracted DNA, we could type all the three loci with all of the
      specimens tested. The incidence of the saliva stain in the practical case was
      estimated to be 3.18 x 10(-5) in Japanese population. We found that the aging of
      saliva stains at least six months did not significantly influence the DNA typing.

PMID- 8258903
TI  - [Recent advances in the study on the mechanism of brain injury].
AB  - A cerebral contusion and DAI (diffuse axonal injury) are practically very
      important in a medico-legal case of the closed head injury. In this paper, we
      will report the epitome of the recent advances in the study on the mechanism of
      them. Coup contusion can be mainly attributed to the skull inbending and/or the
      skull fracture which develop in the impact region. As to the mechanism of the
      contrecoup contusion, several theories are reported. During rotational movement
      of the head, intracerebral shear strains would be produced because of brain lag
      (Holbourn's rotation theory). Anatomical features of the skull plays an important
      role (Gurdjian). Relative movement between a brain and a skull induces
      intracranial cavitation due to pressure gradient (Gross's cavitation theory).
      Brain is injured by deformation pressure induced by skull deformation and
      acceleration one done by a movement of the head (Lindenberg). The last one is
      Courville's transmitted waves of force theory. As to DAI, there is Gennarelli's
      theory. During a rotational movement of a brain caused by high rate of angular
      acceleration operating for a long period, intracerebral shear strains occur and
      injure a brain. As to the brain injuries which include a cerebral contusion and
      DAI, two theories are reported. Centripetal progression of strains to the core of
      a brain injuries the brain (Ommaya). Natural frequency of impact determines the
      nature of resulting injury to the brain (Willinger).

PMID- 8258904
TI  - Histo-pathological findings of abraded skins in the cases of automobile dragging.
AB  - We histologically examined skin which had been abraded by automobile dragging. In
      the first case, the victim was a 57-year-old drunken male. He was hit by a
      passenger car while walking on a road and dragged for a distance of 30 m. He soon
      died from the pelvic bone fractures. Extensive and deep abrasions were observed
      on both shoulders and the back. In the second case, a 20-year-old drunken male
      was lying on a road. He was run over by a passenger car and dragged for a
      distance of 800 m. During the dragging the car's underbody strongly compressed
      his thoraco-abdominal region and killed him by causing insufficiency in
      breathing. Deep abrasions were found in the right temporal region and right back
      at the waist. In the third case, when a 50-year-old woman was riding a moped it
      collided with a passenger car at an intersection and she fell to the ground. Soon
      after, she was run over by another passenger car and dragged for a distance of
      718 m. The cause of death was profuse bleeding from the crushed right axillary
      artery and vein. Autopsy revealed very extensive and severe abrasions in the
      right upper arm, right axilla, lateral surface of the right chest and abdomen,
      right back, back pelvic region, and lateral surface of the right lower leg and
      foot. Especially in the arm, axilla and chest, the skin and soft tissues were
      worn away, muscles and bones were exposed, and the right axillary artery and vein
      were crushed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258905
TI  - [Toxicological findings in a death involving hydrogen sulfide].
AB  - A case of fatal hydrogen sulfide poisoning in a sewage disposal plant is
      described. Hydrogen sulfide levels were determined in several postmortem body
      tissues and fluids using gas chromatography with a flame photometric detection
      (GC-FPD). The concentrations of hydrogen sulfide in the blood, muscle, liver,
      lung, kidney, heart and brain were 0.305, 0.690, 1.089, 1.338, 1.170, 1.366 and
      0.875 (micrograms/g or ml), respectively. The results are discussed in the light
      of the existing literature on the toxicological significance of hydrogen sulfide
      concentrations.

PMID- 8258906
TI  - [A case of sudden death of a patient with glycogen storage disease type 1-
      delayed aftereffect of a traffic accident].
AB  - A case of sudden death of a 22-year-old man with glycogen storage disease type 1
      is reported. Autopsy revealed striking hepatomegaly with round edges. The liver
      was yellowish and weighed 2840 g. Histologic findings showed excessive deposition
      of PAS-positive material in the hepatocytes and in the proximal renal tubular
      epithelium cells, which means the accumulation of glycogen. A mass surrounding
      splenic artery was seen in the hilus of the spleen. There was about 2000 ml of
      fresh blood and clots in the abdominal cavity due to bleeding from a ruptured
      mass. The mass was composed of a hematoma with connective tissue surrounding it
      and was a pseudoaneurysm. The mass was considered to have been formed from
      bleeding due to injury to a branch of a splenic artery. Consideration of these
      findings led to the conclusion that death was caused by loss of blood from
      rupture of the mass and that the mass was formed due to injury of the branch of
      the splenic artery in a traffic accident 2 years earlier but not the pathogenesis
      of glycogen storage disease.

PMID- 8258907
TI  - [B cell population and its autoimmune activity in the thymus of patients
      associated with myasthenia gravis].
AB  - Immunohistochemical studies using antibodies to B lymphocyte and to
      immunoglobulin G bearing cell were carried out for resected thymus-specimens of
      10 patients associated with myasthenia gravis. In each case, abundant B cells
      (L26 positive cell) resided in the follicles and the medulla of thymus,
      especially, were congregated in the follicles developing germinal center and
      around Hassall's corpuscles. Amount of B cell population was various among each
      case regardless of type of myasthenia gravis or age. B cells were greatly
      increased in the thymus of patients with values of anti-acetylcholine receptor
      antibody titers over 100 nmol/l. Although numerous B cells were present in the
      thymus of these patients, IgG bearing cells were extremely rare. In the most
      cases, B cells lacked IgG expression. From the results, numerous B cells pre
      activating autoimmune antibody production were accumulated in the thymus of
      patients associated with myasthenia gravis.

PMID- 8258908
TI  - [Excellent exposure for the mitral valve by means of dissection of the
      interatrial groove].
AB  - A technique to approach the mitral valve through a left atrial incision under
      dissecting the interatrial groove is described. The dissection of the interatrial
      groove makes the left atrial incision more anterior and medial. Therefore
      excellent mitral valve exposure was obtained. 40 of 61 mitral valvular procedures
      during past 1.5-year period were approached through this incision. We could
      achieve better exposure of the mitral valve than that of conventional atrial
      incision technique. This technique takes not so long time and rarely carries
      complications including dysarrhythmia and bleeding.

PMID- 8258909
TI  - [Unusual non-infective inflammatory responses around a collagen impregnated
      vascular prosthesis].
AB  - Causes of some complications such as pyrexia, fluid accumulation and unusual scar
      formation around the graft in "Hemashield" implantation were examined both in
      vivo and in vitro. In an animal study, the grafts were implanted in the thoracic
      descending aorta of 9 dogs, and were explanted at 2 weeks after implantation.
      Macroscopic evaluation of the explants revealed that the graft had no infection,
      but fluid accumulation and a thick scar layer formation were noticed in the
      pleural cavity and around the graft. Microscopical observations demonstrated that
      the impregnated collagen was almost absorbed and numerous plasma cells,
      lymphocytes and macrophages had infiltrated in the interstices of the Dacron
      fibers, but neither fibroblasts nor capillary blood vessels. Numerous erythrocyte
      were also noticed in the graft wall. In vivo experiment of the extract from
      Hemashield, endotoxin and/or (1-3) beta-D-glucan were detected by the special
      quantitative methods; Toxicolor and Endospecy. These results indicated that the
      graft had some contaminants which contained a certain amount of endotoxin, (1-3)
      beta-D-glucan, resulting in non-infective inflammatory responses around the
      graft.

PMID- 8258911
TI  - [Effect of hemodynamics on transdiaphragmatic central venous pressure:
      experiments with rapid bleeding and rapid infusion].
AB  - Effects of hemodynamics which would be a possible problem in monitoring diaphragm
      function through transdiaphragmatic central venous pressure were studied
      experimentally. Mongrel dogs were anesthetized and allowed to breath
      spontaneously. (1) Rapid exsanguination (30 ml/kg. body), (2) rapid infusion (15
      ml/kg. body) were performed. Superior vena cava mean pressure (PSVC) and inferior
      vena cava mean pressure (PIVC) were measured and pressure changes during
      respiration (delta P) were recorded. Changes in the transdiaphragmatic central
      venous pressure (delta PDI = delta PIVC - delta PSVC) were calculated. And
      hemodynamic parameters (heart rate, cardiac output, mean arterial pressure, PSVC,
      PIVC) were measured simultaneously. The delta P and hemodynamic parameters were
      measured before and after (1) or (2). As the results, no significant changes were
      observed in delta PDI even if hemodynamics changed. The results suggest that
      measurement of transdiaphragmatic central venous pressure can be employed
      clinically as a parameter for monitoring diaphragm function to detect hemodynamic
      changes which are less serious than those appeared by mass bleeding or excess
      fluid transfusion.

PMID- 8258910
TI  - [Emergency surgical salvage for a closing aortic dissection: 2 case reports].
AB  - We report here the emergency surgical salvage for closing an aortic dissection in
      2 female patients (case 1; 52 years old, case 2; 72 year old). They were admitted
      to our clinic for severe back pain (case 1) and a loss of consciousness (case 2).
      Acute aortic dissection (Stanford A type) with cardiac tamponade was confirmed by
      chest CT, aortography, and cardiac ultrasonography. Diagnosis was determined as a
      closing aortic dissection from a thrombosed pseudolumen on enhanced chest CT. An
      emergency operation was performed on the ascending aorta replacement and included
      resection of the entry port. The postoperative courses were uneventful, except
      for temporary hemodialysis in case 1. A closing aortic dissection is a new
      subcategory for an acute aortic dissection. Diagnosis is difficult, but it is
      regarded as having a good prognosis following timely emergency treatment.
      However, provided there is no complication, we recommend that surgical treatment
      should be performed aggressively to avoid rupture and/or cardiac tamponade.

PMID- 8258912
TI  - [Thoracoscopic partial resection of the lung by use of Nd-YAG laser and standard
      suturing technique].
AB  - The patient was a 62-year-old woman who was referred to our department for
      bilateral diffuse abnormal shadows along with a sigmoid colon cancer that had
      been resected one month previously. Thoracoscopic partial resection of the left
      S8 region was performed. Nd-YAG laser with a contact tip was used for the
      resection. Hemostasis at the bed of the resection was assured by applying a free
      laser beam to oozing and non-coagulated surface. Additionally, the resected end
      was closed by standard continuous double over-and-over sutures in order to
      minimize the air leakage. Endo-Bulldog clamp facilitated the operation,
      minimizing hemorrhage from the resected end. This device can clamp any part of
      the lung and save one percutaneous puncture site necessary for thoracoscopic
      procedures. Postoperative course was uneventful. Pathological diagnosis was
      reported as an alveolar cell carcinoma of the lung.

PMID- 8258913
TI  - [A new technique for harvesting of internal thoracic artery].
AB  - A new, unique harvesting technique of internal thoracic artery is described. We
      have found that the technique can be applied easily and quickly and gives
      excellent exposure of the pedicle from origin to bifurcation.

PMID- 8258914
TI  - [Clinical application of the thoracic balloon for postpneumonectomy patients].
AB  - Pneumonectomy may result in complications such as continuous intrathoracic
      bleeding and mediastinal shift. We used a thoracic balloon made of silicone
      rubber in 15 postpneumonectomy patients in an attempt to prevent such
      complications. Two types of thoracic balloons were used in our series. Type 1
      thoracic balloon is a simple balloon requiring cooperation with a drainage tube,
      and Type 2 is a combination balloon and drainage tube. During surgery, air was
      injected into the thoracic balloon through an air filter. After removal of the
      thoracic balloon, infusion of sulfur hexafluoride, SF 6, into the thoracic cavity
      was performed on the 7th to 10th postoperative days. Placement of thoracic
      balloons in the pleural space after pneumonectomy is a simple, safe and useful
      method of preventing both intrathoracic bleeding and mediastinal shift.

PMID- 8258915
TI  - [Surgical treatment of cardiac myxomas].
AB  - Between April 1975 to March 1991, 17 patients (5 man and 12 women, mean age 49.8
      years old) underwent surgical treatment for cardiac myxomas. Fifteen patients had
      left atrial myxomas, and the other 2 had the ventricular myxomas (left
      ventricular myxoma 1 and right ventricular myxoma 1). In cases with left atrial
      myxomas, the tumor was resected through the transatrial approach alone in 12
      patients, and the left atriotomy was added in other 3. Left ventriculotomy was
      required to resect the left ventricular myxoma in addition to the atrial
      approach. Right ventricular myxoma, which attached the outflow tract, could be
      removed through the small right vertical ventriculotomy. All patients recovered
      well, and there was no recurrence in any patient during the follow-up period.

PMID- 8258916
TI  - [Emergency coronary artery bypass grafting in a chronic hemodialysis patient: a
      case report].
AB  - Emergency coronary artery bypass grafting (CABG) was performed on a 48-year-old
      male with a long-term hemodialysis history. Following the operation, the patient
      developed acute elevation of potassium. We applied hemodialysis and obtained
      beneficial beneficial results. No remarkable change on hemodynamics and coagulant
      system was observed. Hemodialysis should be recommended on an acute phase for the
      patients of good cardiac function with less bleeding during the operation.

PMID- 8258917
TI  - [Gastrointestinal complication after open cardiac operation].
AB  - Seven cases of abdominal complications necessitated laparotomies within 30 days
      after open heart surgery are presented. They consist of five cases of mesenteric
      infarction, one acalculous cholecystitis and one hemorrhagic ulcer of the rectum.
      The incidence is 0.9 percent at our institute. They also had a very complex
      course after their cardiac surgery such as cardiogenic shock, respiratory failure
      and renal failure prior to the development of their acute surgical abdomen. It is
      proposed that the cause of acute abdomen is attributed basically to the low
      cardiac output state. Surgery must be performed without delay because unnecessary
      passage of time is accompanied by unacceptable mortality rate.

PMID- 8258918
TI  - [A case of left atrial myxoma with ventricular septal defect and patent foramen
      ovale].
AB  - A 51-year-old female was referred to our institute because of chest oppressive
      feeling. Echocardiography and magnetic resonance imaging revealed a left atrial
      tumor with ventricular septal defect. At operation patent foramen ovale was
      recognized. After excision of the tumor including intraatrial septum, which
      defect was repaired using a Teflon patch, and the ventricular septal defect was
      closed directly.

PMID- 8258919
TI  - [Pulmonary venous obstruction after repair of total anomalous pulmonary venous
      drainage: report of a case with reoperation].
AB  - A 8-month-old infant with Darling' type Ib of total anomalous pulmonary venous
      drainage underwent surgical correction. Common pulmonary vein drained into
      superior vena cava. Pulmonary venous channel was constructed between orifice of
      common pulmonary vein and atrial septal defect (ASD) with pericardial baffle
      drainage. Pulmonary venous obstruction occurred at the site of ASD and
      pericardial baffle was atrophic. ASD was enlarged and new pulmonary venous
      channel was reconstructed with EPTFE graft. Post-reoperative clinical course was
      uneventful.

PMID- 8258920
TI  - [A case report of congenitally bicuspid aortic valve and ascending aortic
      aneurysm treated by wheat operation].
AB  - A 59-year-old man who complained of palpitation was diagnosed as having a
      congenitally bicuspid aortic valve, severe aortic regurgitation, and an ascending
      aortic aneurysm. He underwent aortic valve replacement and conduit replacement by
      the modified Wheat technique. Since this technique requires no coronary artery
      anastomosis, it causes no problems associated with reconstruction of the coronary
      artery. Postoperative angiogram revealed no aneurysm formation of the aortic root
      or paravalvular leakage. This case suggest that aneurysm of the ascending aorta
      with aortic regurgitation is more effectively treated by the modified Wheat
      technique if cephalad displacement of the coronary ostium is not extensive.

PMID- 8258921
TI  - [A surgical case of cor triatriatum].
AB  - A case report of a variant type of cor triatriatum was presented. The patient was
      critically ill when she was admitted to our hospital. An emergent operation was
      performed under the cardio-pulmonary bypass. The right atrium was incised, then
      the interatrial septum was incised. Inspection revealed an abnormal membrane in
      the left atrium. All the pulmonary veins were drained into the accessory chamber.
      The left atrial appendage was also connected with the accessory chamber. The
      membrane was not including the mitral valve tissue. It was resected completely.
      Postoperative course was uneventful.

PMID- 8258922
TI  - [A successful repair of traumatic thoracic aortic injury and descending colon
      perforation at acute phase].
AB  - A 41-year-old man suffered from traffic accident was referred to us because of
      chest and back pain. The CT examination showed periaortic hematoma and
      aortography revealed aneurysmal formation at the distal site to the left
      subclavian artery. We repaired the aortic injury with prosthetic graft at the
      acute phase successfully. As the results of the conservative treatment of the
      traumatic aortic injury are poor, we recommend operation at the acute phase.

PMID- 8258923
TI  - [A case report of aneurysm of the diverticulum of the ductus arteriosus].
AB  - A 59-year-old man who was admitted with hoarseness and diagnosed as aneurysm of
      the diverticulum of the ductus arteriosus was reported. In our case, enhanced
      computed tomography and aortography gave reliable informations. Operation was
      performed through a posterolateral thoracotomy under partial cardiopulmonary
      bypass. The aneurysm was successfully resected and defect of the aortic wall was
      covered with Dacron patch. Postoperative course was uneventful. To our knowledge,
      this is 12th surgically treated case in Japan.

PMID- 8258924
TI  - [A case report of pulmonary metastasis of malignant fibrous histiocytoma (MFH)
      accompanied by mediastinal lymph node metastasis].
AB  - Mediastinal lymph node metastasis associated with pulmonary metastasis is rarely
      seen in soft tissue sarcoma. A case is presented in which investigation of
      primary lung cancer (cT2N2M0) in a 78-year-old woman with a history of MFH of the
      left thigh revealed pulmonary metastasis of MFH accompanied by paratracheal (#2)
      and anterior mediastinal (#3a) lymph node metastases.

PMID- 8258925
TI  - [Cerebrospinal fluid fistula following an operation of mediastinal schwannoma: a
      case report].
AB  - A 33-year-old man was operated for the mediastinal schwannoma. During the
      operation, the 9 th intercostal nerve was avulsed and revealed liquorrhea.
      Lyodura and fibrin glue was applied for sealing the site of dural defect. But
      post-operative course was not successful. So, we used the external cerebrospinal
      fluid drainage system. After this procedure, thoracic fluid from the chest tube
      was reduced and we could remove the chest tube in the 20th post operative day.
      This case indicates that in case of thoracotomy, it is difficult to expect easy
      closure of cerebrospinal fluid fistula under conservative therapy. Therefore it
      was considered that specific repair during the operation and spinal drainage in
      the post-operative early phase should be performed.

PMID- 8258926
TI  - [Study of combination therapy for thymoma: a case of stage IV which presented as
      total spinal block caused by epidural metastasis and which preoperative
      combination therapy was effective for minimizing the tumor].
AB  - We experienced 24 cases of thymoma in the past 17 years. Associated syndromes as
      myasthenia gravis and pure red cell anemia (PRCA) were found in 7 patients.
      Preoperative therapies were done for the cases of stage IV. Total resection of
      the tumor was performed except 3 cases which ended in exploratory thoracotomy.
      Postoperative therapies were done except the cases of stage I. Each one case of
      stage III and IV a whose operation ended in exploratory thoracotomy died of
      tumors, but latter case had some period of PR after chemotherapy. A case of stage
      I with PRCA died from pneumonia but other cases of autoimmune disease had been
      well controlled by medical treatment. A case of stage IVb was first admitted to
      the hospital for paralysis of bilateral lower limb. After resecting the epidural
      tumor of thoracic spine, chemotherapy (CAV 1 kur) and radiotherapy (4,200 rad)
      was performed which was effective for minimizing the antero-mediastinal tumor.
      Though operation ended in exploratory thoracotomy, majority of the tumor was
      found to be replaced for fibrous tissue which suggested the effectiveness of the
      combination therapy. But this case died from pancreatitis during the
      postoperative therapy. In conclusion, combination therapy of surgical resection
      and adjuvant radiotherapy & chemotherapy including the care for autoimmune
      disease is important in the treatment of thymoma.

PMID- 8258927
TI  - [Multidisciplinary treatment for a patient with recurrent thymoma associated with
      myasthenia gravis (MG), pure red cell aplasia (PRCA), and hypogammaglobulinemia].
AB  - The patient is 62-year-old female. When she was 43 years old, MG occurred. At age
      of 49 years thymoma was found and complete thymectomy (stage III) and
      postsurgical irradiation were performed. At age of 57 years pleural dissemination
      of the thymoma was found. Chemotherapy was effective but did not obtain total
      tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth,
      the regimen used at first recurrence became ineffective and the interval between
      tumor regrowth became shorter. This year, when she is 62 years old, PRCA and
      hypogammaglobulinemia were accompanied with the forth tumor regrowth.

PMID- 8258928
TI  - [Successful surgical repair of emphysematous giant bullae of the elderly with
      severely depressed pulmonary function].
AB  - A 71-year-old male was admitted to an emergency hospital owing to severe dyspnea
      of sudden onset. Bilateral tension pneumothorax with two giant bullae occupying
      more than the third of the right lung was disclosed on the chest X-ray. Bilateral
      chest drainages and cardiopulmonary resuscitation were performed. He could be
      freed from ventilatory support several days after tracheostomy and was referred
      to our hospital. The pulmonary function was severely depressed: VC (%) 1.20 l
      (40%) and FEV1.0 (%) 0.55 l (46%). In spite of oxygen inhalation he could not
      keep sitting due to dyspnea (Hugh-Jones grade V). Right multiple bullectomy was
      performed successfully and his postoperative course was uneventful. He was
      discharged eight weeks later. Seven months after surgery his pulmonary function
      was remarkably improved: VC (%) 2.05 l (64%) and FEV1.0 (%) 0.94 l (46%). He
      became to walk almost equally with a healthy man one year later (Hugh-Jones grade
      II).

PMID- 8258929
TI  - [Extracapsular tumor invasion in renal cell carcinoma: with special reference to
      limitation of surgical enucleation].
AB  - To elucidate the feasibility of surgical enucleation, the incidence of
      extracapsular tumor invasion in 30 cases of renal cell carcinoma with a diameter
      less than 5 cm was examined, based on the classification of extracapsular tumor
      invasion into three patterns, namely microinvasion, nodular invasion, and
      daughter tumors. Of the 30 cases of renal cell carcinoma, 22 cases (73%) revealed
      extracapsular tumor invasion. And the incidence of microinvasion, nodular
      invasion and daughter tumors was 7 cases (23%), 9 cases (30%) and 6 cases (20%),
      respectively. But the incidence of these three patterns of extracapsular tumor
      invasion correlated neither with the size of renal cell carcinoma nor with pT
      classification. There was a tendency for extracapsular tumor invasion to occur
      near the renal hilar site of the renal cell carcinoma, where the tumor vessels
      were rich, penetrated and twined around the tumor capsule, resulting in the
      disruption of the tumor capsule. These three patterns of invasion was located
      within 1 cm in distance from the tumor capsules in all cases. In conclusion,
      because of limited radicality achieved by tumor enucleation even in the case of
      pT1, partial nephrectomy was recommended in the presence of a normal
      contralateral kidney.

PMID- 8258930
TI  - [The value of an aseptic intermittent catheterization program in the early
      management of spinal cord injury patients].
AB  - From 1979 to 1989, 269 patients with spinal cord injury were managed by an
      aseptic intermittent catheterization program during the acute phase of their
      injuries at the Spinal Injuries Center. One hundred fifty one patients with
      incomplete cord lesion and 36 males with complete tetraplegia were managed by
      program I, which protects the shocked bladder from overdistention. In contrast,
      82 patients with complete cord lesion excluding male tetraplegia were managed by
      program II, which allows overdistention of the bladder. Of the 187 patients
      managed by program I, 137 (73.3%) achieved trigger voiding function, 61.3% of
      whom were completely dry. Of the 82 patients managed by program II, 62 (75.6%)
      were put to self- or assisted catheterization, 67.7% of whom were dry. The
      incidence of a grade I, which means normal bladder configuration, was 88.0% for
      program I and 87.3% for program II during the follow up course. Upper urinary
      tract deterioration occurred in only one case. Surgical treatment for urinary
      tract complications was performed in 14 cases (5.2%). These results suggest that
      the patients with incomplete cord lesion managed by non-distension regimen of the
      bladder (program I) and those, especially female, with complete cord lesion
      managed by overdistention regimen of the bladder (program II) achieve urinary
      continence with excellent urinary prognosis.

PMID- 8258931
TI  - [Clinical results of radical surgery for prostate cancer].
AB  - We reported the clinical results of radical surgeries for 44 patients with
      prostate cancer performed between November 1984 and December 1992. The patients
      were aged from 57 to 79-year-old (mean 67.2) and classified as clinical stage A2
      (6 cases), B1 (7), B2 (12), C (16) and D1 (3) respectively. Radical prostatectomy
      was performed in 42 cases and radical cystoprostatectomy with urinary diversion
      in 2 patients, and thirty-nine of 44 cases underwent endocrine or chemoendocrine
      therapies prior to the surgeries. In all patients with stage A2-B1, the
      operations were curative, on the other hand, more than 80% of clinical stage B2
      patients had pT3 tumors and 33.3% of them had lymph node involvements. With
      regard to stage C patients, the incidence of lymph node metastasis and positive
      margin was more frequent. Postoperative adjuvant therapies were added to the
      patients with pT3,4 tumors and nodal involvements. Patients without residual
      tumors (n = 20) remained disease-free for 8-89 months (mean 32.8). Of 24 patients
      who had incomplete resection of tumors, 2 died of other diseases, other 2 were
      alive recurrent and 20 were alive free from disease for 3-99 months (mean 33.8).
      The surgical indication for low-stage (A2-B2) prostate cancer has been widely
      accepted, however that for high-stage cancer (C,D1) has remained controversial.
      It was our belief that radical surgeries for high-stage cancer could become a
      potentially curative therapeutic modality in combination with pre- and post
      operative adjuvant therapies.

PMID- 8258932
TI  - [Outpatient ESWL in 500 kidneys].
AB  - Between March 1989 and January 1992, 600 cases (636 kidneys) with upper urinary
      tract stones were treated with ESWL, using a Lithostar. Of these, 78.6% were
      carried out in our outpatient service, and in the last two years approximately
      90% of cases have been treated as outpatient. We evaluated first 500 kidneys,
      treated with ESWL as outpatient. There were 481 cases involving 500 kidneys (19
      bilateral cases). The ages of the 367 men and 114 women ranged from 16 to 77
      years. There were 227 kidney stones and 273 ureter stones. Most of the stones
      were less than 20 mm. The average number of sessions and shock waves for each
      patient were 1.4 times and 6,988 waves, respectively. While 74% of the patients
      could be treated in only one session, 9% of them needed 3 sessions or more.
      Auxiliary measures were needed in 23 cases (D-J stent insertion in 5 cases and
      ureteral catheterization in 18 cases) and 474 cases (94.8%) were treated by in
      situ procedures. At 3 months after treatment, 470 cases were evaluated and the
      stone-free rates of kidney stones and ureter stones were 70.3% and 84.5%,
      respectively with an overall stone-free rate of 78.1%. With regard to
      complications, the rate of the clinic visit because of pain after treatment was
      observed in 4.6% and higher than 38 degrees C in 2.5%. However, no serious
      perioperative complications occurred. From these results, outpatient ESWL was
      considered to be safe and efficient without serious complications.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258933
TI  - [An analysis of prognostic factors in patients with prostatic cancer after
      hormone therapy and radiotherapy].
AB  - To investigate prognostic factors for prostatic cancer, 110 patients who had
      received hormonal treatment (HT) and 43 patients who had received radiotherapy
      (RT) were studied. Age of the patients ranged from 49 to 92 years old (median 71
      years old) and follow-up period ranged from 3 to 164 months (median 50 months).
      Survival rate was calculated by Kaplan-Meier method with statistical analysis
      based upon Cox's proportional hazards regression model. This analysis identified
      performance status as the most important factor for al patients, followed by
      histological grade for patients HAVING received HT, and lymph node metastasis for
      patients received having RT. The result suggests that routine clinical data
      provide a good indicator as to the prognosis of prostatic cancer.

PMID- 8258934
TI  - [Adhesion of calcium oxalate crystal to Madin-Darby canine kidney cells:
      quantitative determination and effects of glycosaminoglycans (GAG) and cell
      injuries on adhesion].
AB  - The present investigation was designed to study adhesion of calcium oxalate
      crystals on the surface of intact MDCK cells quantitatively, and to estimate the
      effects of glycosaminoglycans (GAGs) and cell injuries on these adhesions.
      Calcium oxalate monohydrate (COM) crystals adhere to the cell surface by an
      active force, and the attachment is in a time and concentration dependency with
      plateau. Pre-treatments with low concentration of GAGs (chondroitin sulphate C,
      hyaluronic acid, heparan sulphate, heparin and sodium pentosan polysulphate)
      produce significant reductions of the adhesion. There are significant decreases
      of the adhesions with pre-treatments of Triton-X100, 0.1 N HCl and gentamicin.
      These phenomena might be induced by some alterations of cell surface structures
      or characters. The current quantitative system on MDCK cells should serve as a
      useful model for the investigations of interactions with crystals and tubular
      cells. Our studies may also support the hypothesis of attachment of microcrystals
      to the cellular membrane, which is one of the most important and the earliest
      process of the pathophysiology of kidney stone.

PMID- 8258935
TI  - [Clinical study of immunotherapy with interferon alpha and gamma in metastatic
      renal cell carcinoma].
AB  - A clinical study was conducted to evaluate the efficacy of combination therapy
      with interferon (IFN) alpha and gamma in 16 patients with advanced renal cell
      carcinoma whom we observed between August 1986 and June 1992. Eight patients had
      already had stage IV disease when they were seen first and five of them underwent
      nephrectomy. The other eight patients developed metastases after nephrectomy. The
      time to occurrence of the metastasis was 4-110 months. The dosage of the regimen
      was IFN alpha, 3 x 10(6) U, intramuscularly for 7 consecutive days at weeks 1, 3,
      5 and 7 and IFN gamma, 6 x 10(6) JRU by intravenous drip on days 2, 4 and 6 of
      weeks 2, 4, 6 and 8. At and after week 9, the combined use of IFN alpha, 3 x
      10(6) U, and IFN gamma, 1-6 x 10(6) JRU, was continued at least on a once-a-week
      basis as maintenance therapy as long as possible. The effect was evaluated as PR
      in 2 patients, MR in 2, NC in 3 and PD in 9. The response rate was 12.5% and the
      efficacy rate including MR was 25%. The time to onset of the effect was 8-24
      weeks. Of the four patients showing MR or better responses, three had stage IV
      disease and one had metastatic disease after the operation. The duration of
      effect was 2-8 months. Side effects were fever, general malaise, anorexia,
      leukocytopenia and impaired liver function, and were noted frequently.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258936
TI  - [99mTechnetium-diethylenetriaminepentaacetic acid renoscintigraphy as a measure
      of renal function and urodynamics after uretero-ileoceco-proctostomy].
AB  - Ten patients having a uretero-ileocecoproctostomy (ileocecorectal bladder) were
      evaluated by 99mtechnetium diethylenetriaminepantaacetic acid renoscintigraphy,
      which was repeated at an approximately 1 year interval in 7 patients. The
      computed total glomerular filtration rates at the 1st and 2nd surveys were 100 +/
      23.2 and 92.7 +/- 23.0 ml/min (mean +/- S.D.), respectively indicating a minimal
      change with no statistically significant difference. The normal or incompletely
      obstructive renogram patterns were consistent with the pyelographic findings in
      27 of 28 renal units, and 5 of 6 renal units with dilated nonobstructive
      renograms subsequently became normal both on the renograms and pyelograms.
      Comparing the data in the 1st and 2nd surveys, the frequency of colonic reflux
      decreases from 8/10 to 3/7 of the patients, the rectal bladder capacity increased
      from 82 +/- 18.8% to 92 +/- 20.8% of the excreted urine, and the total residual
      urine rate decreased from 40.4 +/- 12.9% to 28.0 +/- 16.6% (p = 0.1298),
      respectively. The results indicate that the ileocecorectal bladder, though it has
      no antireflux mechanism against colonic regurgitation, well functions as an
      internal continent urinary reservoir. Also, since this comprehensive information
      is obtained by a single procedure, the radionuclide evaluation can be practiced
      as a cost-beneficial measure for follow-up of patients with urinary diversions.

PMID- 8258937
TI  - [A clinical study on renal pelvic and ureteral tumor associated with bladder
      tumor].
AB  - Of 65 cases of renal pelvic and/or ureteral tumor treated at Department of
      Urology, The University of Tokyo, during the period from January 1975 through
      December 1991, 26 had bladder tumors as well. These cases were divided into three
      groups; 1) bladder tumor preceding upper urinary tract tumor, 2) bladder tumor
      found simultaneously with upper urinary tract tumor, and 3) bladder tumor
      following upper urinary tract tumor. In group 1 (nine cases), the last bladder
      tumor preceded renal pelvic and/or ureteral tumors by 3 to 42 months (mean 14.6
      months), and in seven cases, bladder tumor recurred 3 to 29 months (mean 9.0
      months) after nephroureterectomy. The interval between the diagnosis of preceding
      bladder tumor and upper urinary tract tumor was highly correlated with the latent
      period of postoperative recurrence of bladder tumor (r = 0.948). Highly malignant
      pathological grade of bladder tumor featured seven cases of group 2, with the
      survival rate being significantly (p < 0.01) lower than that of other groups. In
      the group 3 consisting of ten cases, bladder tumors subsequently developed 6 to
      37 months (mean 15.0 months). The latent period of bladder tumor was
      significantly (p < 0.01) longer than that in group 1. These results indicated
      that the bladder tumors associated with renal pelvic and/or ureteral tumors have
      distinct characteristics depending on the sequence of association.

PMID- 8258938
TI  - [Study on the enzymatic properties of N-acetyl-beta, D-glucosaminidase A (NAG A)
      from the tissue of renal cell carcinomas: comparison of the enzymatic properties
      with those of normal renal tissues, with special regard to sugar-chain
      structures].
AB  - The enzymatic properties of N-acetyl-beta,D-glucosaminidase A (NAG A) partially
      purified from the tissues of seven cases of human renal cell carcinomas were
      studied individually and compared with those of normal renal tissues. In the
      carcinoma tissues, the Km value of the enzyme toward a synthetic glucosaminide
      substrate was 0.180 +/- 0.07 mM, the optimal pH of the enzyme ranged from pH 4.7
      to 4.9 and the enzyme showed fairly stable for metal ions. These enzyme
      characteristics were similar to those of the normal tissues. On the contrary, the
      sugar-chain structures of the enzyme from the carcinoma tissues studied by lectin
      affinity chromatographies, were statistically different from those of the normal
      tissues. Namely, both complex type of sugar-chains as well as hybrid type sugar
      chains without fucose linkage to the innermost N-acetylglucosamine (GlcNAc) were
      significantly increased in the enzyme from the carcinoma tissues, while high
      mannose type sugar-chains and hybrid type sugar-chains with fucose linkage to the
      innermost GlcNAc were significantly decreased in the carcinoma tissues compared
      to the normal tissues. These results indicate that the processing of sugar-chains
      of the enzyme has possibly changed in the carcinoma tissues.

PMID- 8258939
TI  - [A clinico-pathological study of primary carcinoma in situ of the upper urinary
      tract: urinary cytology and pathological study of cases reported in Japan,
      including our three cases, by mapping].
AB  - We herein report three cases of primary carcinoma in situ (CIS) of the upper
      urinary tract. The significance of urinary cytology and pathological study by
      means of mapping of isolated specimens was investigated in cases reported in
      Japan, including our cases. 1. The most common clinical symptom of CIS of the
      upper urinary tract was hematuria. Particularly, gross hematuria showed a high
      incidence. 2. In cases of CIS involving the ureter, hydronephrosis frequently
      resulted from ureteral stenosis and obstruction. 3. Urinary cytology was a useful
      diagnostic examination, in particular, the cytology of catheterized urine or
      washings increased the diagnostic accuracy. It appeared that for definite
      diagnosis, positive urinary cytology should be obtained repeatedly. 4. The
      mapping analysis of isolated specimens revealed that it was characterized that
      CIS was multiple and coexistent with dysplasia. 5. Total nephroureterectomy is
      the treatment of first choice. An investigation of the distribution of CIS and
      dysplasia by mapping and grading of CIS seemed to be useful for following up the
      postoperative course.

PMID- 8258940
TI  - [Primary non-Hodgkin lymphoma of the prostate: a case report].
AB  - A 24-year-old man presented with gross hematuria and pain on micturition.
      Cystoscopically the prostatic urethra appeared to be pale, edematous and partly
      elevated mucosa, from which multiple biopsy specimens were taken by TUR-P. A
      pathological diagnosis of malignant lymphoma (diffuse and large-cell type,
      according to the LSG classification: B-cell origin according to
      immunohistochemistry) was established. The results of the physical examination
      and imaging studies were compatible with the diagnosis of primary lymphoma of the
      prostate. The patient underwent a combination chemotherapy consisting of
      vincristine, cyclophosphamide, adriamycin and prednisolone. After completion of 6
      courses of chemotherapy over 7 months, another TUR biopsy of the prostate
      confirmed complete remission. Now, 1 year after completion of chemotherapy, he
      remains free of the disease. To our knowledge, this is the 21st clinical case of
      lymphoma of the prostate ever reported in the Japanese literature.

PMID- 8258941
TI  - [A case of prostatic carcinoma with ectopic ACTH syndrome].
AB  - A 67-year-old man was admitted to the orthopedic ward, complaining of severe pain
      in his right greater trochanter. He was diagnosed as spinal cord tumor and
      underwent laminectomy for extirpation of the tumor. Histological examination
      revealed bone metastasis of unknown origin. Laboratory data revealed hypokalemia
      and hyperglycemia. Endocrinological data showed elevation of plasma cortisol and
      ACTH, and increased excretion of urinary 17-OHCS. Ten specimens needle biopsy of
      the prostate showed poorly differentiated adenocarcinoma, thus patient was
      diagnosed as prostate cancer with bone metastasis (stage D2) and perhaps ectopic
      ACTH production. Castration was performed, however 2 days after the surgery he
      died suddenly. We suspected that cerebral hemorrhage was the cause of his death.
      On autopsy ectopic ACTH production in the prostate was confirmed.

PMID- 8258942
TI  - [A case report: reversible male infertility due to congenital adrenal
      hyperplasia].
AB  - We have studied a 32-year-old patient who was infertile because of azoospermia,
      We made the final diagnosis of non-classical congenital adrenal hyperplasia (CAH)
      caused by 21-hydroxylase deficiency with adrenal rest tumor of bilateral testes
      and bilateral adrenal myelolipoma. The patient was given 1.5 mg/day
      dexamethasone. Decreases in the levels of 17 OHP and adrenal androgen were
      rapidly observed. After 5 months of treatment, semen analysis showed a sperm
      density of 2 x 10(4)/ml with 50% motile spermatozoa. His wife became pregnant and
      delivered of a healthy daughter. We conclude that chronic suppression of
      gonadotropins secretion caused by overproduction of adrenal androgens in CAH
      would appear to be the cause for the failure of testicular development and
      spermatogenesis.

PMID- 8258943
TI  - Mechanisms of renal hemodynamic regulation in response to protein feeding.

PMID- 8258944
TI  - Renal synthesis of arginine in chronic renal failure: in vivo and in vitro
      studies in rats with 5/6 nephrectomy.
AB  - Synthesis of arginine (Arg) from citrulline (Cit) by the kidney is a major source
      of Arg for the body. The high level of plasma Cit in chronic renal failure is
      often thought to result from the impairment of the renal conversion of Cit to
      Arg. To verify this assumption, we performed two studies in Sprague-Dawley rats
      with 5/6 nephrectomy (CRF rats) and in sham-operated rats (CONT rats). In study I
      synthesis of Arg by isolated proximal convoluted tubules (PCT; the nephron
      segment exhibiting the highest Arg synthesis) was measured in vitro with two
      concentrations of Cit (200 or 50 microM) corresponding to those observed in
      plasma of rats with or without renal failure. In study II the net renal uptake of
      Cit and release of Arg were determined in vivo by measuring PAH clearance and
      arterial and renal venous Arg, and Cit concentrations in anesthetized rats. The
      in vitro results showed that Arg synthesis increased only in proportion to the
      hypertrophy of remnant PCT (+50%), and was highly and similarly dependent on Cit
      concentration in PCT of remnant and normal kidneys (Arg production with 200
      microM Cit was 3 times higher than with 50 microM Cit for both CONT and CRF). The
      in vivo results showed that renal Cit uptake and Arg release were not altered in
      CRF: -286 +/- 28 versus -326 +/- 16 nmol Cit.min-1 (NS), and + 390 +/- 47 versus
      + 399 +/- 22 nmol Arg.min-1 (NS) in CONT and CRF rats, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258945
TI  - Juxtamedullary afferent and efferent arterioles constrict to renal nerve
      stimulation.
AB  - Sympathetic neural control of afferent and efferent arterioles of inner cortical
      (juxtamedullary) glomeruli has not been established, in part, because of
      difficulty accessing these vessels, normally located deep below the kidney
      surface. In this study we utilized the rat hydronephrotic kidney model to
      visualize the renal microcirculation and to quantitate the responses of
      juxtamedullary arterioles to brief (30 sec) renal nerve stimulated (RNS).
      Juxtamedullary afferent and efferent arterioles constricted in a frequency
      dependent fashion to RNS, achieving a maximal constriction of 35% to 8 Hz
      stimulation. In these same kidneys, outer cortical afferent arterioles also
      constricted to RNS but outer cortical efferent arterioles did not. Microinjection
      of norepinephrine (NE) around single outer cortical efferent arterioles (to avoid
      the constriction of preglomerular vessels) constricted the efferent arterioles.
      However, the afferent arterioles of the same glomeruli were considerably more
      responsive to microinjected NE. Thus, the lack of constriction of outer cortical
      efferent arterioles to RNS may relate, in part, to their low sensitivity to NE,
      the primary neurotransmitter. These direct observations indicate that the
      juxtamedullary efferent arterioles are responsive to renal nerve stimulation
      whereas the outer cortical efferent vessels are not. These results, which should
      be cautiously extrapolated to normal filtering kidneys, indicate that glomerular
      hemodynamic changes evoked by the sympathetic nervous system are different for
      outer cortical and inner cortical glomeruli.

PMID- 8258946
TI  - Self-regulation of autoreactive kidney-infiltrating T cells in MRL-lpr nephritis.
AB  - MRL-lpr kidney-infiltrating (KI) T cell clones (CD3+, TCR alpha/beta+, B220+, CD4
      , CD8-) are autoreactive, exclusively proliferate to renal tissues, and secrete
      interferon-gamma (IFN-gamma). We now report that IFN-gamma treatment of tubular
      epithelial cells (TEC) decreases their ability to induce KI T cell proliferation.
      The decreased ability of IFN-gamma-treated TEC to induce T cell proliferation is
      evident by 24 hours and can be restored by re-exposure to TEC not treated with
      IFN-gamma. IFN-gamma-treated TEC supernatant does not diminish KI T cell
      proliferation and IFN-gamma-treated TEC fixed with glutaraldehyde remain less
      capable of inducing KI T cell proliferation. Although we have not identified the
      TEC surface molecule(s) modified by IFN-gamma, neither class I, class II, ICAM-1
      nor IFN-gamma bound to the surface of TEC are responsible. In conclusion, IFN
      gamma induces a surface alteration(s) on TEC capable of limiting their ability to
      induce KI T cell proliferation. The ability of autoreactive KI T cells to release
      IFN-gamma represents a self-regulatory mechanism for limiting T cell expansion.

PMID- 8258947
TI  - Water transport model during CAPD: determination of parameters.
AB  - To minimize the total amount of glucose required for removing the same volume of
      water as a bolus, a continuous infusion of glucose during CAPD was proposed and
      studied. Both a computer simulation of water transport through the peritoneal
      membrane and in vivo assessment with rats were carried out to evaluate the
      feasibility of the newly proposed mathematical model in which lymphatic drainage
      of dialysate from the peritoneal cavity to lymphatic system was considered in
      addition to conventional water transport. Mass transport area coefficients (KA)
      of 0.041 to 0.063 ml/min/100 g body wt and 0.045 to 0.066 ml/min/100 g body wt
      were measured for glucose and urea during CAPD with male Wistar rats. Hydraulic
      conductivity of peritoneal membrane (Lc) was 7.9 x 10(-5) to 1.5 x 10(-4)
      ml/min/mm Hg/100 g body wt, which was calculated by a linear relationship between
      volume and osmotic pressure. Simulated water transport model using determined
      parameters indicated that the ratio of lymphatic transport to convective
      transport would be changeable in CAPD with glucose infusion at varying infusion
      rates, while up to 16% of the glucose uptake could be reduced compared with that
      of the common CAPD at the same dwell time.

PMID- 8258948
TI  - Intermittent and continuous exposure to 1,25(OH)2D3 have different effects on
      growth plate chondrocytes in vitro.
AB  - Intermittent 1,25(OH)2D3 administration is widely used to suppress parathyroid
      glands in secondary (renal) hyperparathyroidism. It is unknown whether the
      effects of continuous and intermittent 1,25(OH)2D3 differ on vitamin D target
      organs other than parathyroids. Using primary cultures of rat chondrocytes
      (tibia) we compared the effects of continuous versus intermittent exposure to
      physiologic concentrations of 1 alpha,25(OH)2D3 on proliferation (radiothymidine
      incorporation), cell count, protein synthesis ([3H]-leucine incorporation),
      alkaline phosphatase activity (as a marker of differentiation) and 1
      alpha,25(OH)2D3 receptor (VDR) regulation. Cells were synchronized and then
      exposed for variable periods to a medium containing 10% delipidated FCS and 10(
      8) M to 10(-12) M 1 alpha,25(OH)2D3 (or 1 beta,25(OH)2D3 as specificity control).
      Intermittent (8 hr exposure every 48 hr) as well as continuous (sham washing)
      administration of 1 alpha,25(OH)2D3 had a biphasic effect on proliferation, that
      is, stimulation at low (10(-12) M) and inhibition at high (10(-8) M)
      concentrations. At 10(-12) M intermittent 1 alpha,25(OH)2D3 yielded higher cell
      counts than continuous 1,25(OH)2D3. This was seen in the log phase, which was day
      3 (continuous 141 +/- 2.3% of solvent control; intermittent 185 +/- 2.0%) and in
      the plateau phase of growth, which was day 6 (128 +/- 2.6 vs. 169 +/- 2.7% of
      solvent control). Dependence on extracellular Ca is suggested by the effects of
      varying nominal Ca concentrations in the medium and of Ca channel blockers. Even
      two hours of exposure to 1 alpha,25(OH)2D3 (10(-12) M) yielded maximal activation
      of AP during postincubation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258949
TI  - Catechol-O-methyltransferase mRNA in the kidney and its appearance during
      ontogeny.
AB  - Catechol-O-methyltransferase (COMT), primarily present as a soluble cytosolic
      form (S-COMT), inactivates catechols. The recent cloning of the rat and human S
      COMT from placenta has allowed us to synthesize complementary oligonucleotide
      probes to study the localization of COMT mRNA during development in the rat
      kidney and in the adult human kidney using in situ hybridization histochemistry.
      In the adult rat kidney, COMT mRNA was detected in segment S3 of proximal tubule
      cells in the outer stripe of the outer medulla, and thick ascending limb of loop
      of Henle (TAL) in the inner stripe. COMT mRNA was detected in the prenatal rat
      kidney as early as on day 18. In the human kidney, strong hybridization signal
      was seen in the medulla and in tubule segments of the cortex. In the adult rat
      kidney, COMT mRNA was in addition demonstrated in the transitional epithelium of
      the ureter. The results suggest synthesis of COMT and inactivation of catechols
      along the distal parts of proximal tubules, in TAL cells, and in the epithelium
      of the ureter.

PMID- 8258950
TI  - Effects of 5'-N-ethylcarboxamideadenosine (NECA) on erythropoietin production.
AB  - The present studies were undertaken to assess the effects of 5'-N
      ethylcarboxamideadenosine (NECA), an adenosine analogue, on erythropoietin (Epo)
      production. NECA (0.05 and 0.1 mumol/kg i.v.) produced significant increases in
      serum Epo levels (368.8 +/- 56.1 and 384.6 +/- 45.9 mU/ml, respectively) in
      exhypoxic polycythemic mice after a four hour exposure to hypoxia when compared
      with hypoxia controls (133.2 +/- 18.2 mU/ml). The hypoxic kidney Epo levels were
      46.4 +/- 13.4 mU/kg kidney which were significantly higher than normoxic kidney
      Ep levels (< 1.24 mU/kg kidney). Theophylline (20 mg/kg i.p.), an adenosine
      receptor antagonist, significantly inhibited the stimulatory effects of NECA on
      serum Epo levels. In vitro cultures of an Epo producing hepatocellular carcinoma
      (Hep3B) cell line with NECA (> or = 10(-6) M) for 20 hours under hypoxic
      conditions (1% O2) produced significant increases in medium levels of Epo when
      compared with hypoxia controls. Hepatocellular carcinoma cells treated with NECA
      at a concentration range of 10(-7) M to 5 x 10(-5) M for one hour in a hypoxic
      atmosphere also had significantly higher cAMP levels than that of hypoxia
      controls. Scatchard analyses of [3H]NECA binding to membrane preparations of
      hepatocellular carcinoma cells showed low affinity binding sites with a
      dissociation-constant (Kd) of 0.44 microM and a binding capacity of 863 fmol/mg
      protein. These findings suggest that the increase in Epo production in response
      to NECA under hypoxic conditions can be attributed, at least in part, to
      stimulation of adenosine A2 receptors which is coupled to adenylyl cyclase
      activation.

PMID- 8258951
TI  - Luminal and intracellular cGMP inhibit the mTAL reabsorptive capacity through
      different pathways.
AB  - Since, in the presence of ANF, urinary cGMP was shown to be of glomerular origin,
      a possible paracrine effect of luminal cGMP on the medullary thick ascending limb
      (mTAL) function was investigated. Net chloride reabsorption (JCl) was determined
      on isolated microperfused tubules from mouse kidney. Addition of 10(-6) M cGMP to
      the lumen significantly decreased JCl by 46.5 +/- 4.6%. A concentration-dependent
      decrease of the transepithelial voltage was observed, with a 10(-8) M threshold.
      Added to the bath, ANF (10(-7) M) as well as urodilatin (6 x 10(-8) M) decreased
      JCl by 29.8 +/- 3.9% and 36.9 +/- 5.1%, respectively, an effect reproduced by 8
      bromo cGMP and associated with a significant increase in tubular cGMP content.
      The inhibitory effect of ANF was similar whether or not cGMP was present in the
      lumen. Furthermore, increasing intracellular cGMP content by 8-bromo cGMP did not
      prevent a further effect of luminal cGMP. Finally, H-8, which blocked the effect
      of ANF, urodilatin, and 8-bromo cGMP, failed to abolish the luminal cGMP-induced
      decrease of JCl, suggesting that this effect did not require a cGMP-dependent
      protein kinase activation. It is concluded that luminal cGMP inhibits the
      reabsorptive function of the mTAL through a pathway different from the
      intracellular cGMP production.

PMID- 8258952
TI  - Defective glomerular [3H]lysoPAF metabolism in the autologous phase of rabbit
      nephrotoxic nephritis.
AB  - Glomerular infiltration of blood-derived mononuclear cells contributes to the
      glomerular injury in the autologous phase of nephrotoxic nephritis (NTN). LysoPAF
      has recently been shown to be chemotactic for human monocytes, thus its
      accumulation might account for monocyte recruitment. We investigated [3H]lysoPAF
      metabolism in isolated glomeruli from normal and NTN rabbits studied both in the
      heterologous and in the autologous phases of the disease. [3H]lysoPAF was
      converted to [3H]1-O-alkyl-glycerol and [3H]1-O-alkyl-2-acyl-GPC by phospholipase
      C and acyltransferase, respectively, both in normal and NTN glomeruli. Glomerular
      metabolism of [3H]lysoPAF was normal during the heterologous phase of NTN. By
      contrast, in isolated glomeruli from NTN rabbits studied in the autologous phase
      of the disease, a significantly lower [3H]lysoPAF degradation occurred with
      respect to normal ones. This defective degradation resulted in a significantly
      reduced formation of [3H]1-O-alkyl-glycerol. The apparent Km for enzymatic
      conversion of [3H]lysoPAF to [3H]1-O-alkyl-glycerol, determined at 15 minutes as
      a function of [3H]lysoPAF concentration, was doubled in glomeruli from rabbits
      studied in the autologous phase of NTN as compared to normal ones, while Vmax
      values were similar in the two groups. These results show a defective glomerular
      lysoPAF degradation in the autologous phase of NTN, likely due to a decreased
      affinity of phospholipase C to lysoPAF. Altered lysoPAF metabolism results in
      glomerular accumulation of lysoPAF in the autologous phase of NTN, as shown by
      significantly higher levels of lysoPAF measured in nephritic glomeruli as
      compared to normal ones.

PMID- 8258953
TI  - Enhancement of vascular action of arginine vasopressin by diminished
      extracellular sodium concentration.
AB  - The present study was undertaken to examine the effects of diminished
      extracellular sodium concentration on the vascular action of arginine vasopressin
      (AVP) in cultured rat vascular smooth muscle cells (VSMC). The preincubation of
      cells with the 110 mM extracellular Na+ ([Na+]e) solution supplemented with 30 mM
      choline chloride for 60 minutes enhanced the effect of AVP- (1 x 10(-8) M)
      induced VSMC contraction. The treatment of 110 mM [Na+]e solution also enhanced
      the cellular contractile response to the protein kinase C (PKC) activators,
      phorbol 12-myristate 13-acetate and 1-oleoyl-2-acetyl-glycerol. Furthermore,
      preincubation with the 110 mM [Na+]e solution also potentiated the effect of 1 x
      10(-8) M AVP, but not 1 x 10(-6) M, to increase the cytosolic-free Ca2+ ([Ca2+]i)
      concentration. The 110 mM [Na+]e media decreased the basal intracellular Na+
      concentration and increased intracellular 45Ca2+ accumulation, basal [Ca2+]i and
      AVP-produced 45Ca2+ efflux. These effects of 110 mM [Na+]e solution to enhance
      the vascular action of AVP were abolished by using Ca(2+)-free 110 mM [Na+]e
      solution during the preincubation period. The preincubation with the 110 mM
      [Na+]e solution did not change either the Kd and Bmax of AVP V1 receptor of VSMC
      or the AVP-induced production of inositol 1,4,5-trisphosphate. The present in
      vitro results therefore indicate that the diminished extracellular fluid sodium
      concentration within a range observed in clinical hyponatremic states enhances
      the vascular action of AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258954
TI  - Renin stimulating properties of parathyroid hormone-related peptide in the
      isolated perfused rat kidney.
AB  - Previous studies showed that PTHrP exhibits renal vasodilating, arteriolar cAMP
      stimulating and receptor binding properties. The present experiments were
      designed to study whether PTHrP may influence renin secretion. Rat kidneys were
      isolated and single-pass perfused at constant flow and stabilized pressure.
      Exposures to PTHrP or PTH stimulated a dose-dependent renin release reaching
      similar Vmax. The affinity (0.1 nM) and threshold concentration (0.01 nM) for
      PTHrP were about 10 times lower than for PTH. Compared to 10 microM
      isoproterenol, the maximum renin responses to PTHrP were similar but of shorter
      duration. The PTHrP dose-response curve was not affected by 10 microM
      indomethacin. Administered simultaneously, PTHrP and PTH displayed no additive
      effects. PTHrP-induced renin release as well as the role of extracellular calcium
      were further studied in nonfiltering kidneys, which were perfused at a constant
      flow and stable pressure in a closed circuit. Basal renin release was inversely
      related with perfusate calcium and was depressed by the calcium ionophore BAY
      K8644. PTHrP (100 nM) induced a 1.6-fold increase of basal renin release in
      normocalcic perfusate. Removing calcium abolished renin responses. PTHrP reversed
      the inhibiting effects of hypercalcic media or BAY-K8644 on basal renin release.
      The results support calcium-mediated renin stimulating properties for PTHrP, via
      PTH receptors, independently from baroreceptors, macula densa and prostaglandins.

PMID- 8258955
TI  - Interstitial fibrosis in obstructive nephropathy.
AB  - Interstitial fibrosis and tubular basement membrane (TBM) thickening are evident
      within 16 days of unilateral ureteral obstruction (UUO) in the rabbit, and
      resemble the changes previously reported in hydronephrotic human kidneys. The
      cortical interstitial volume fraction in this rabbit model at 16 days is 43.3 +/-
      6.1% (+/- 1 SD) in UUO kidneys, 4.9 +/- 3.1% in contralateral kidneys (CLK), and
      2.8 +/- 0.8% in kidneys from sham-operated animals (ANOVA, P < 0.0001).
      Immunohistochemically, UUO is associated with increased interstitial collagens I
      and III, fibronectin, heparan sulfate proteoglycan and tubulointerstitial
      nephritis antigen. Aberrant collagen expression is also evident as interstitial
      collagen IV becomes prominent. Focal, peritubular accumulation of collagens I and
      II also appear to encircle the TBM. These changes are accompanied by an early,
      transient increase in renal cortical mRNA encoding the alpha 1 monomers of
      collagens I, III and IV, implicating increased matrix synthesis in the
      pathogenesis of obstructive nephropathy. In situ hybridization localized
      increased expression of alpha 1 (I) and alpha 1 (IV) mRNA to cells in the
      interstitial space, with clusters of alpha 1(I) positive cells associated with
      dilated tubules, muscular arteries and the periglomerular interstitium.

PMID- 8258956
TI  - Studies of alteration of hepatic cholesterol metabolism in puromycin-induced
      nephrotic syndrome in rats.
AB  - Hypercholesterolemia frequently accompanies the nephrotic syndrome, but the
      mechanism responsible for elevation of plasma cholesterol is poorly understood.
      Specifically, the contribution of abnormal hepatic cholesterol metabolism to
      elevated concentrations of serum cholesterol has never been studied in depth. The
      objective of the present study was to define the alteration of hepatic
      cholesterol metabolism in puromycin induced nephrotic syndrome in rats. Studies
      involved measurements of specific activities of four enzymes participating in the
      maintenance of hepatic cholesterol metabolism: HMG-CoA-reductase, the rate
      limiting enzyme of cholesterol synthesis; cholesterol 7 alpha-hydroxylase, the
      rate limiting enzyme in bile acid synthesis; acyl CoA: cholesterol
      acyltransferase, the enzyme responsible for esterification of cholesterol; and
      cholesterol ester hydrolase (CEH), an enzyme which hydrolyzes cholesterol.
      Multiple injections of puromycin resulted in a production of nephrotic syndrome
      with massive proteinuria, hypoalbuminemia, hypercholesterolemia, ascites and
      edema. HMG-CoA-reductase (nmol/hr/mg protein) and cholesterol 7 alpha-hydroxylase
      activities (nmol/hr/mg protein) in rats with nephrotic syndrome were not
      statistically significant as compared to control rats (4.0 +/- 0.7 and 2.0 +/-
      0.6 vs. 3.3 +/- 0.4 and 1.6 +/- 0.2), respectively. Our results also demonstrate,
      for the first time, that the normal diurnal rhythm in HMG-CoA reductase activity
      is no longer present in the nephrotic animals. The activities in the nephrotics
      in the day was 4.0 nmol/hr/mg and at night, 3.9 nmol/hr/day, compared to the
      control values of 3.3 nmol/hr/mg in the day and 6.9 nmol/hr/mg at night. ACAT
      activities were 428 +/- 78 versus 302 +/- 64 pmol/min/mg/protein (P =
      NS).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258957
TI  - In situ expression of cytokines in IgA nephritis.
AB  - We studied mRNA and protein expression of interleukins (IL) and tumor necrosis
      factor (TNF) in renal tissues biopsied from 40 patients with IgA nephritis.
      Immunofluorescent staining with antibodies to IL-1 alpha, IL-1 beta, IL-6, IL-8,
      TNF-alpha, and TNF-beta was intense in the cytoplasm of cells in glomeruli, which
      were dual-stained with an anti-monocyte-macrophage antibody. In addition,
      moderate immunofluorescence for TNF-alpha, and weak staining for IL-1 alpha and
      IL-6 were occasionally found in resident glomerular cells. Immunoperoxidase-in
      situ hybridization dual-labeling revealed that IL-1 alpha, IL-6, and TNF-alpha
      mRNA signals were present in intraglomerular cells reactive with anti-monocyte
      macrophage antibody, which further supported the immunofluorescent findings.
      Cells expressing IL-1 alpha, IL-1 beta, IL-6, IL-8, TNF-alpha, and TNF-beta were
      also observed in the interstitium. Most of these cells were also labeled with the
      anti-monocyte-macrophage antibody. The number of IL-1 alpha, IL-6, and TNF-alpha
      positive cells infiltrating the glomerulus significantly correlated with
      mesangial hypercellularity. IL-8 and TNF-alpha-positive intraglomerular cells
      were correlated with the magnitude of proteinuria. The population of interstitial
      cells positive for IL-1 alpha, IL-6, IL-8, and TNF-alpha was associated with the
      grade of tubulointerstitial changes and proteinuria. There was no correlation
      between local IL-1 alpha, IL-6, and TNF-alpha expression in glomeruli or
      interstitium and serum or urinary levels of the respective cytokines.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8258958
TI  - Fibrillary glomerulonephritis without immunoglobulin deposits in the kidney.
AB  - Three patients are presented, who by electron microscopy, showed prominent
      fibrillary deposits in the glomeruli, and in two, also around the tubules. By
      immunohistology these two cases had no immunoglobulins in either glomeruli or
      around the tubules. In the third case, which probably represents a slightly
      different form of the disease, minor deposits of IgM were found in the glomeruli,
      while fibrillary deposits were extensive and widespread. It is suggested that
      precursors of fibrillary deposits may not be the same in all cases.

PMID- 8258959
TI  - n-3 fatty acids reduce proteinuria in patients with chronic glomerular disease.
AB  - Dietary supplementation with n-3 polyunsaturated fatty acids (n-3 PUFA) has been
      shown to reduce proteinuria in experimental models of renal diseases, but their
      potential role in the treatment of human renal disease is unknown. We
      administered n-3 PUFA in the form of triglycerides [with eicosapentaenoic
      (EPA)+docosahexaenoic (DHA) = 3 g/day into 4 patients] and of ethyl esters
      (EPA+DHA = 7.7 g/day) into 10 patients (one patient twice) with chronic
      glomerular disease (membranous glomerulonephritis and focal glomerular
      sclerosis), all diagnosed histologically. Serum albumin was > 2.4 g/dl and serum
      creatinine < 2.5 mg/dl in all patients. Treatment was given for periods of six
      weeks, followed by a prolonged follow-up for 27 weeks in 10 cases. Dietary
      supplementation with n-3 PUFA caused the expected reduction in platelet
      generation of thromboxane B2 (mean +/- SEM, from 490 +/- 70 ng/ml at baseline, to
      342 +/- 147 ng/ml at 6 weeks, P < 0.05) of serum triglycerides (from 236 +/- 60
      to 170 +/- 43, P < 0.01), and a prolongation of the bleeding time (from 5.8 +/-
      0.4 min to 7.7 +/- 0.4 min, P < 0.01) in patients treated with ethyl esters. A
      modest but significant reduction in serum total cholesterol was noticed (from 275
      +/- 27 to 252 +/- 24 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258960
TI  - Non-invasive monitoring of blood volume during hemodialysis: its relation with
      post-dialytic dry weight.
AB  - Hemodialysis has a profound effect on fluid balance. Since fluid is initially
      withdrawn from the intravascular compartment, blood volume will decrease rapidly.
      A fluid shift (refill) from the overhydrated interstitium towards the
      intravascular compartment counteracts hypovolemia. Underestimation of
      postdialytic dry weight will cause interstitial dehydration and consequently a
      low refill capacity. This can cause hypovolemia-induced hypotension, a serious
      problem in the daily practice of hemodialysis: during one out of three sessions a
      hypotensive episode occurs. Clinical criteria to estimate post-dialytic dry
      weight are insensitive. We have developed non-invasive methods to estimate dry
      weight and changes in blood volume (BV) more accurately. The aim of this study
      was to investigate the relation between hydration state of the patient and
      changes in BV during treatment. Therefore, 37 hemodialysis patients were divided
      into three groups according to their post-dialytic extracellular fluid volume
      (EFV), which was measured by means of the non-invasive conductivity method: de-
      (N = 11), normo- (N = 18), and overhydrated (N = 8). Using an on-line optical
      reflection method, changes in BV were measured continuously during hemodialysis.
      BV decrease, corrected for ultrafiltration, was stronger in the dehydrated (4.4
      +/- 1.5%/liter) than in the normohydrated (3.3 +/- 1.5%/liter) and overhydrated
      (2.7 +/- 1.9%/liter) groups. In the dehydrated group, the frequency of
      hypotensive episodes (48.5 +/- 20.2%) was significantly greater compared to the
      normohydrated (20.5 +/- 23.5%) or overhydrated (6.5 +/- 6.5%) group, P <
      0.005.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258961
TI  - Long-term glycemic control and the rate of progression of early diabetic kidney
      disease.
AB  - In this prospective study of 11.9 years duration (range 9 to 14), we examined the
      progression of albuminuria prior to and after the onset of microalbuminuria
      [albumin excretion rate (AER): 20 to 200 micrograms/minute]. Glycated hemoglobin
      (HbA1), AER and blood pressure were measured every six months. Twenty-two (13
      type I, 9 type II) patients were identified in whom AER increased progressively
      (progressors). These patients were compared with 22 others matched for age,
      duration and type of diabetes in whom AER did not change significantly during the
      study period (non-progressors). In the progressors, the rate of increase in AER
      correlated with mean HbA1 for the study period in patients with type I (r = 0.68,
      P < 0.01) and type II diabetes (r = 0.71, P < 0.05). Furthermore, AER began
      increasing well before the conventional 20 micrograms/minute threshold of
      microalbuminuria had been reached and within the first five years of diagnosis of
      type I diabetes. We conclude that in predisposed diabetic patients, long-term
      glycemic control is correlated with the rate of development of early renal
      abnormalities. Repeated measurements of AER from the time of diagnosis may be
      useful in the early detection of patients who will develop microalbuminuria and
      ultimately overt diabetic nephropathy.

PMID- 8258962
TI  - Aplastic osteodystrophy without aluminum: the role of "suppressed" parathyroid
      function.
AB  - We evaluated 259 dialysis patients using serum parathyroid hormone (PTH, IRMA;
      normal range 1 to 5.5 pM or 10 to 55 pg/ml), the deferoxamine infusion test and
      iliac crest bone biopsy to determine the various forms of renal osteodystrophy
      and their risk factors. Although half of the biopsied patients had low turnover
      osteodystrophy, evidence of aluminum toxicity was present in only 1/3 of them.
      Additional risk factors for this bone lesion included treatment with peritoneal
      dialysis, ingestion of calcium carbonate, diabetes mellitus and advanced age. The
      PTH levels in patients with the aplastic lesion were significantly lower than in
      patients with normal or high bone turnover lesions [7.7 +/- 6.1 vs. 36.9 +/- 3.2
      pM (77 +/- 61 vs. 369 +/- 32 pg/ml), P < 0.0001]. Aside from hypercalcemia, these
      patients were relatively asymptomatic. In a second study, 10 patients on
      peritoneal dialysis with the aplastic lesion had their dialysate calcium lowered
      from 1.62 to 1.0 mM. This resulted in a significant increase in PTH levels, from
      [3.7 +/- 0.8 to 10.6 +/- 1.9 pM (37 +/- 8 to 106 +/- 19 pg/ml), P < 0.001] which
      persisted over the nine-month observation period. In conclusion, the aplastic
      lesion is the most common form of renal osteodystrophy, with aluminum
      intoxication implicated in only 1/3 of the cases. In the remainder, factors
      identified include therapy with peritoneal dialysis using supraphysiological
      dialysate calcium, oral CaCO3 intake and diabetes mellitus.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8258963
TI  - Post-transplantation nephrosis in congenital nephrotic syndrome of the Finnish
      type.
AB  - Congenital nephrotic syndrome of the Finnish type (CNF) is an autosomal
      recessively inherited disease manifesting as massive proteinuria, edema and
      ascites in the neonatal period. The disease is believed to be limited to the
      kidneys and recurrences after renal transplantation have not been reported. At
      our center 29 transplantations have been performed on 28 CNF patients. One to 33
      months after transplantation, seven grafts (24%) of six patients have developed a
      steroid-resistant nephrotic syndrome. The clinical data and renal histology of
      these patients were analyzed in order to elucidate the cause of the proteinuria.
      At the onset of six of the seven episodes of nephrosis, the patient had evidence
      of a preceding CMV- or EBV-infection and the remaining patient had sinusitis.
      Upon light and electron microscopy examination, endothelial swelling of the
      glomerular capillaries resembling transplant glomerulopathy (TG) was seen, but
      unlike TG, the glomerular basement membranes were normal. The response of
      proteinuria to steroid or cyclophosphamide therapy was poor, with total remission
      in only two patients and partial remission in one patient, all treated with
      methylprednisolone and cyclophosphamide immediately after the diagnosis. Four
      grafts have been lost. Our data show that CNF patients have an increased tendency
      for post-transplantation nephrosis.

PMID- 8258964
TI  - A simple method to determine millimolar concentrations of sodium in nanoliter
      samples.
AB  - Measurement of sodium in the nanoliter samples obtained from in vitro studies of
      isolated, perfused nephron segments has traditionally been associated with time
      consuming sample preparation and/or expensive instrumentation. A new instrument
      is described which can measure picomole quantities of sodium without the need for
      special processing. The instrument is based on the continuous flow devices
      developed by Vurek and a sodium-sensitive glass detector. The response to varying
      concentrations of NaCl was logarithmic as predicted from the Nernst equation. The
      response to 50 mM NaCl was 22.1 +/- 0.2 mV; 100 mM, 29.9 +/- 0.2 mV; 150 mM, 35.2
      +/- 0.2 mV; and 200 mM, 39.3 +/- 0.6 mV (mean +/- SD). The slope of the standard
      curve was 27.8 mV/log unit change in sodium concentration. Potassium, calcium and
      ammonium, possible interfering ions, had no effect on the response to 100 mM
      NaCl. When the response to 100 mM NaCl was measured in buffered solutions of
      varying pH, it was 29.1 +/- 0.2 mV at pH 6.21, 28.9 +/- 0.4 mV at pH 7.04 and
      28.7 +/- 0.4 mV at pH 8.54, indicating that pH did not alter the response to 100
      mM NaCl. By treating the detector with NaOH and HCl, the response to 50, 100 and
      150 mM improved to the point that the slope of the standard curve was 51.2 mV/log
      unit change in sodium concentration. The calculated resolution after treatment
      was 1.0 mM in the 50 to 100 mM range and 1.3 mM in the 100 to 150 mM range using
      a 10.9 nl pipet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258965
TI  - Regression of left ventricular hypertrophy in hypertensive dialyzed uremic
      patients on long-term antihypertensive therapy.
AB  - There have been no studies of the possibility of reversing the left ventricular
      hypertrophy (LVH) of chronically hemodialyzed hypertensive uremics (HDH) with
      long-term antihypertensive therapy. We have measured left ventricular sizes of
      eight (6 male, 2 female, aged 29 to 61 years) HDH with M-mode echocardiography,
      before and 12, 18 and 24 months after the start of a combined antihypertensive
      therapy which included ACE-inhibitors, beta-blockers and calcium-antagonists. Pre
      treatment values for mean blood pressure (MBP), 116.6 +/- 2.9 mm Hg, end
      diastolic diameter (EDD), 62.6 +/- 6.6 mm, interventricular septum (IVS), 14.2 +/
      3.0 mm, and left ventricular mass index (LVMi), 239 +/- 61 g/m2, were all
      significantly higher than those for nine sex- and age-matched hemodialyzed
      normotensive subjects (HDN) with comparable hemoglobin (Hb) levels. During the
      antihypertensive treatment, both the systolic and diastolic BP decreased steadily
      (P = 0.0001; P = 0.0003; ANOVA) and significantly by the third month (P < 0.05; P
      < 0.01), reaching levels comparable to those of the HDN group after 12 months. At
      this time the LVMi (204 +/- 67) and the IVS (13.1 +/- 2.7), although both
      significantly lower than baseline, were still higher than in the HDN group, while
      the EDD was similar. After 24 months, however, both the IVS (12.3 +/- 3.1) and
      the LVMi (161 +/- 65) were no longer different from those of the HDN
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8258966
TI  - Molecular biology of erythropoietin.

PMID- 8258967
TI  - Fibromyalgia.

PMID- 8258968
TI  - Lupus and its management.
AB  - The recognition and treatment of SLE requires an approach similar to other
      chronic diseases. A thorough initial evaluation with regular monitoring of
      outwardly silent manifestations (e.g. renal) minimizes potentially devastating
      complications. For disease which does not threaten the patient's life or carry
      the threat of end-organ failure, treatment analogous to non-lupus patients is
      usually appropriate, including minimization of steroids. The widening use of
      cytotoxic agents promises to continue to decrease the mortality from SLE. These
      agents must be used sparingly and in consultation with a rheumatologist to reduce
      the incidence of infection, malignancy and sterility.

PMID- 8258970
TI  - Raynaud's phenomenon and connective tissue diseases.

PMID- 8258969
TI  - Diagnosis and management of common tendinitis and bursitis syndromes.

PMID- 8258971
TI  - A dialogue for the management of common musculoskeletal disorders.

PMID- 8258972
TI  - Testing for circadian differences in lethality for intravenous ouabain in male
      mice.
AB  - Using a randomized, balanced design and double-blind methodology, ouabain
      octahydrate was administered intravenously to male mice at six clock times. Eight
      runs were conducted using six constant dosage levels. All the dose-response
      curves at the clock times of 02:30, 06:30, 10:30, 14:30, 18:30 and 22:30 were
      parallel and no significant differences were noted between the respective LD50
      determinations using nomograph methods. Independent chi-square analysis of all
      lethality data indicated no significant variation in response between clock times
      and between runs but a very highly significant difference between doses. Using
      regression methods, onset time for death was shown to vary inversely with log
      dosage, but those periods of possible increased susceptibility could not be
      correlated with a shortened time to death. These findings are consistent with a
      random variation in lethality in regard to clock time rather than a true
      circadian pattern. The pooled (N = 576) intravenous LD50 for ouabain octahydrate
      was 3.75 mg/kg with 95% confidence limits of 3.60-3.90 mg/kg or, when calculated
      as anhydrous ouabain, 3.01 (2.89-3.13) mg/kg.

PMID- 8258973
TI  - Composition and antimicrobial properties of essential oils of four Mediterranean
      Lamiaceae.
AB  - Essential oils from Satureja montana L., Rosmarinus officinalis L., Thymus
      vulgaris L., and Calamintha nepeta (L.) Savi, were chemically analysed and their
      antimicrobial and fungicide activities evaluated on the basis of their minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). All
      four oils have a biotoxic effect, the most active being those from Calamintha and
      Thymus.

PMID- 8258974
TI  - Antimicrobial activities of crude leaf extracts of Acalypha wilkesiana.
AB  - Water, ethanol, chloroform and hexane extracts of Acalypha wilkesiana leaves were
      investigated for in vitro antimicrobial activities by agar-diffusion and tube
      dilution techniques. The water and ethanol extracts inhibited the growth of
      standard and local strains of bacteria and fungi including Staphylococcus aureus,
      Trichophyton rubrum, Trichophyton mentagrophytes, Candida albicans and
      Aspergillus flavus. The aqueous extract did not exert any inhibitory action on
      Klebsiella pneumoniae and Proteus mirabilis while the ethanol extract was active.
      The minimum inhibitory concentrations of the extracts ranged between 0.25 and 32
      mg/ml, while the minimum cidal concentrations were between 1.0 and 64 mg/ml. The
      aqueous extract was found to be static in action while the ethanolic extract was
      uniformly cidal in effect.

PMID- 8258975
TI  - Medicalethnobotany of some weeds of Mauritius and Rodrigues.
AB  - The people of Mauritius and Rodrigues have always used medicinal plants for
      various ailments, and have for a long time been dependent on surrounding plant
      resources for their food, shelter, fodder, health care and other cultural
      purposes. However, encroaching industrialization and the accompanying changes in
      their lifestyles are responsible for the decrease of practice in the local use of
      plants for medicine. It is, therefore, felt worthwhile to record the native uses
      of these plants before the information is lost. The present paper deals with the
      medicalethnobotany of 53 genera and 94 different species of plants considered as
      weeds.

PMID- 8258976
TI  - Ethnobotanical survey of Zagori (Epirus, Greece), a renowned centre of folk
      medicine in the past.
AB  - Zagori is a group of villages in and around the National Park of Vikos-Aoos, in
      Epirus, north-west Greece. It was renowned in previous centuries as a major
      centre of folk medicine, and its practitioners, called 'vikoyiatri' or
      'komboyiannites', were famous beyond the borders of Greece. Given the rich
      biological and cultural heritage of Zagori, we have tried to evaluate the present
      status concerning the medicinal flora of the area and its uses in the everyday
      life of the Zagori inhabitants. About 100 plants and their uses for therapeutic
      and other purposes are reported. Information included comes from both literature
      sources and interviewed informants. Traditional healing has not been altogether
      wiped out of Zagori. However, it no longer reflects the famous past and rich
      medicinal flora of the area.

PMID- 8258977
TI  - Ethnomedicinal study of major species in the family Labiatae from Kenya.
AB  - The family Labiatae, commonly called the mint family, is one of the flowering
      group of plants that has been found to have great medicinal potential. In this
      study, at least twenty-eight (28) indigenous species which are popular among
      Kenyan herbalists have been collected from the Rift Valley and central parts of
      Kenya. Preliminary chemical analysis of the Ocimum genus has revealed several
      different components of essential oils. There is evidence that further and more
      intensive research on the medicinal aspects of the family is called for.

PMID- 8258978
TI  - Antimicrobial properties of some hydroxycoumarins and Fraxinus ornus bark
      extracts.

PMID- 8258979
TI  - A skin irritant principle from Euphorbia matabelensis Pax.
AB  - A diterpene of the ingenane-type parent alcohol with tetradecanoic acid as the
      acid substituent was isolated by chromatographic methods from the latex of
      Euphorbia matabelensis. The ingenol ester exhibited irritant activity on the
      mouse ear.

PMID- 8258980
TI  - Biological screening of Uruguayan medicinal plants.

PMID- 8258981
TI  - Isolation of verbascoside, an antimicrobial constituent of Buddleja globosa
      leaves.

PMID- 8258982
TI  - MEDFLOR: an ethnobiological database.

PMID- 8258983
TI  - Lymphatic imaging.

PMID- 8258984
TI  - Heterogeneity of tracheobronchial lymphatic smooth muscle responses to histamine
      and 5-hydroxytryptamine.
AB  - We assessed the responsiveness of tracheobronchial lymphatic smooth muscle to
      mediators of inflammation to determine whether homogeneous responses to histamine
      and 5-hydroxytryptamine (5-HT) are demonstrated among species typically used in
      studies of lymph vessels. Fresh porcine and bovine tracheobronchial lymph vessels
      were suspended from force-displacement transducers in baths containing oxygenated
      Krebs solution. Concentration-response curves were generated by cumulative
      addition of histamine (10(-7) to 10(-3) M) or 5-HT (10(-7) to 3 x 10(-4) M).
      Active tension (AT) was expressed in milligrams and as a percentage of initial
      vessel ring response to 65mM KCl. Histamine elicited concentration-dependent
      contraction, yielding maximum AT in porcine rings of 1116 +/- 127 mg (n = 39;
      129.1 +/- 10.5% of KCl response) and in bovine rings of 733 +/- 106 mg (n = 20;
      65.8 +/- 12.9%; P = 0.0005 for percent responses). PD2 values (negative log10 of
      the concentration at half-maximum effect) were 4.49 +/- 0.08 and 4.82 +/- 0.08;
      (P = 0.0034). 5-HT elicited concentration-dependent contraction, yielding maximum
      AT of 560 +/- 50 mg in porcine rings (n = 15; 97.2 +/- 9.7%) and 2892 +/- 454 mg
      in bovine rings (n = 27; 159.0 +/- 29%; P < 0.0001 for percent responses). PD2
      values were 6.25 +/- 0.05 and 5.28 +/- 0.04 (P < 0.0001). The data demonstrate a
      role for inflammatory mediators in the modulation of tracheobronchial lymphatic
      smooth muscle tone that is species- and mediator-specific, and support the
      potential for paracrine regulation of tracheobronchial lymph flow.

PMID- 8258985
TI  - Immune responses and chronic lymphedema in experimental filariasis.
AB  - Chronic lymphedema is a clinically important manifestation of lymphatic
      filariasis but the factors which govern the development and progression of
      lymphedema remain unclear. Because immune responses are major determinants of
      disease expression in filariasis, we compared immune responses in ferrets
      reinfected with B. malayi in which disease expression varied from virtually no
      overt disease to severe chronic lymphedema of the infected limbs. No immune
      correlates specific for development of chronic lymphedema were identified by
      antigen recognition profiles (Western-blots), magnitude of the antibody (IgG)
      responses (ELISA) or blastogenic responses of lymphocytes to filarial extracts.
      Prausnitz-Kustner (PK) tests for filarial specific IgE indicated that the initial
      period of a severe lymphedema, which became chronic, often was associated with
      relatively high IgE titers. The results suggest that a high level of immediate
      hypersensitivity to filarial antigens is a significant factor in initiating
      persistent lymphedema on reinfections of partially resistant hosts. Histologic
      study of persistent edema of up to 2 years duration demonstrated dermal changes
      consistent with chronic lymphedema, but not the dermal proliferation
      characteristic of elephantiasis.

PMID- 8258986
TI  - Ultrasound therapy of chronic arm lymphedema after surgical treatment of breast
      cancer.
AB  - The treatment of chronic arm lymphedema following axillary dissection for breast
      cancer is still a therapeutic challenge. To examine other treatment options, we
      undertook a pilot study on the efficacy of ultrasound therapy (UST) in management
      of these patients. Fifty patients with post-surgical arm lymphedema and without
      regional irradiation underwent ultrasound treatment (2 cycles at 4 month
      intervals) and the results were compared up to 1 year with 100 other patients
      treated by standardized mechanical pressure therapy (MPT) using a pneumatic pump.
      In this report we evaluate 96 patients who have been followed after 1 year, 31 of
      whom belong to UST group and 65 to the MPT group. UST did not show a
      statistically significant difference in whole arm reduction of lymphedema
      although there was initially a greater reduction in size after the first 4 months
      of treatment. The addition of an elastic sleeve did not improve lymphedema in
      either group. Advantages of UST were an overall shorter length of treatment, a
      tendency to greater softening of the arm, patient satisfaction by avoidance of an
      uncomfortable and constrictive device and better relief of osteomyofascial pain,
      greater scapulohumeral motion, and less intercostobrachial pain-dysesthesia.

PMID- 8258987
TI  - Inhibition of the active lymph pump in rat mesenteric lymphatics by hydrogen
      peroxide.
AB  - The lymphatic system plays an important role in the regulation of fluid and
      macromolecular exchange. It is a key "safety factor" against the formation of
      gross edema. Spontaneous contractions in collecting lymphatics of the rat
      intestine are necessary for the normal transportation of lymph. Hydrogen peroxide
      is one of the compounds released in inflammation. Therefore, the effects of H2O2
      on the pumping activity of spontaneously contracting lymphatics were evaluated in
      the anesthetized rat (n = 16). Diameter oscillations of the mesenteric collecting
      lymphatics were monitored before and after the application of H2O2 (4 and 37
      microM). The activity of the lymph pump was evaluated using: contraction
      frequency (F), stroke volume (SV), ejection fraction (EF), and lymph pump flow
      (LPF). These parameters were determined from the lymphatic diameter tracings. The
      following changes in lymphatic activity were seen after a 20 minute exposure to
      37 microM H2O2: 1) F declined 85%, from 11.6 +/- 1.5 to 1.9 +/- 1.9 cpm. 2) SV
      fell over 93%. 3) EF decreased 93%, from 0.57 +/- .07 to 0.05 +/- .04. 4) LPF
      fell dramatically (> 95%) from 41.5 +/- 10.5 to 2.6 +/- 2.5 nl/min. In
      conclusion, H2O2 produced an intense inhibition of the active lymph pump and it
      is possible that the inhibition of the active pump contributes to the edema which
      occurs during inflammation.

PMID- 8258988
TI  - Chronic peripheral lymphatic cannulation in the dog.
AB  - Peripheral lymph collected acutely has been commonly sampled as representative of
      non-visceral interstitial fluid. By developing a prenodal lymphatic-lymphatic (L
      L) shunt, we were able to collect peripheral lymph for 3-5 days in unanesthetized
      dogs. The L-L shunt was constructed entirely of medical grade silicone rubber
      tubing designed with a slip of coupling which allowed the shunt to be
      disconnected for lymph collection and reconnected at night. Average peripheral
      lymph flow (4.9 ml/hr leg) in unanesthetized dogs was almost twice the flow rate
      previously observed in anesthetized dogs. The average lymph/plasma total protein
      concentration ratio (0.16), however, was similar to that previously found in
      anesthetized dogs. Lymph protein concentration fell with the collection during
      the day and became more concentrated at night. Lymph flow did not change greatly
      during daytime collection. Average peripheral lymph collection volume was greater
      than 200 ml/dog. The L-L shunt allows collection of prenodal-lymph in experiments
      where unanesthetized dogs are required (e.g., feeding studies). They also are
      useful when multiple protocols are conducted on the same dog or when large
      volumes of peripheral lymph are required.

PMID- 8258989
TI  - Regulation of granulocytosis in inflammatory disease and in leukemia.

PMID- 8258990
TI  - Induction of cytotoxic lymphocyte subsets against leukemia by stimulation with
      AML blasts.
AB  - Although the application of interleukin-2 (IL-2) activated lymphocytes in
      immunotherapy of acute myelogenous leukemia (AML) is of therapeutic interest, the
      high resistance of AML blasts to lymphocyte lysis may represent an obstacle to
      this type of therapy. However, our data shows that the leukemia resistance can be
      conquered by concomitant culture of lymphocytes with IL-2 and AML blasts. This
      approach induces not only leukemia-directed cytotoxic cells, but also promotes
      their growth. Additionally, multiple cytotoxic lymphocyte populations with
      leukemia lytic activity are induced in AML/IL-2 cultures. These include natural
      killer (NK) cells and subsets of T cells with both the major histocompatibility
      complex (MHC)-restricted and MHC-nonrestricted cytotoxic function. Thus, this
      protocol, which is conducive to general stimulation of cellular immune responses
      against leukemia, may enhance the benefits of lymphocyte therapy.

PMID- 8258991
TI  - Biology of monoclonal antibodies in tumor therapy.
AB  - This paper gives an overview of the biology of monoclonal antibodies in tumor
      therapy. The complexity of the monoclonal antibody concept is discussed with
      functional aspects on tumor antigen, antigen binding, Ig isotypes and effector
      mechanisms involved.

PMID- 8258992
TI  - BCG in the treatment of superficial cancer of the bladder: a review.
AB  - Superficial Bladder Cancer can be treated in several ways. During the last
      decades, intravesical instillation of Bacillus Calmette Guerin (BCG) has emerged
      as an effective therapy. The history of how BCG became an antitumoral treatment
      is long and intriguing, and the theoretical background is fragile. In numerous
      studies, involving over 3,000 patients, intravesical instillation of BCG has been
      shown to be an effective treatment for superficial cancer of the urinary bladder
      in humans. Temporarily, BCG can eradicate residual disease after surgery, it can
      prevent local recurrence, and it can halt deterioration of malignancy in
      recurrences. However, its effect on survival is uncertain. For patients,
      treatment with BCG is prolonged, expensive, associated with side-effects, and may
      even be harmful. The mode of action is obscure. The theoretical framework on
      which this therapy is based is purely speculative, if existing at all. Although
      BCG has been classified as a biological response modifier, and the treatment is
      termed immunotherapy, proof is still lacking that the mechanism is immunological.

PMID- 8258993
TI  - Monoclonal antibodies and superantigens: a novel therapeutic approach.
AB  - We have developed a monoclonal antibody (mAb) based therapy intended for the
      treatment of solid tumors utilizing both main arms of the immune system by
      incorporating the colon carcinoma recognizing mAb C215 and the T cell activating
      bacterial staphylococcal enterotoxin A (SEA) in a single hybrid molecule. The
      recombinant tumor specific superantigen C215-SEA retained excellent antigen
      binding properties while the binding to MHC class II was markedly reduced and
      should allow targeting of a large fraction of T cells to tumors in vivo. C215-SEA
      mediated T cell killing of C215 expressing tumor cells irrespective of their
      expression of MHC class II antigens and induced levels of IFN-gamma and TNF in
      mononuclear cells sufficient to completely suppress the growth of colon carcinoma
      cells in vitro. In initial studies of anti-tumor effects, C215Fab-SEA was found
      to markedly inhibit the growth of colon carcinoma cells transplanted to Scid mice
      adoptively transferred with human mononuclear cells.

PMID- 8258994
TI  - Separation of rare cell subpopulations with the aid of biotin-labelled ligands.
AB  - A universal method for selection of surface marker-positive cells is described.
      The cells, admixed with an excess of surface marker-negative cells, are first
      labelled with a specific biotinylated ligand and then isolated with the aid of
      monoclonal, anti-biotin coated beads. The method enables selection and isolation
      of cells with a frequency as low as 10(-4). The ligand can be an antigen (for
      selection of infrequent antibody-producing cells), an antibody (for selection of
      surface antigen-positive cells) or other molecules (for selection of specific
      receptor-positive cells).

PMID- 8258995
TI  - The colony stimulating factors.
AB  - Hematopoiesis is a dynamic process, which generate in the range of 10(9) cells/kg
      each day of erythroid and myeloid cells respectively. In vitro assays that were
      developed 20 years ago, have been used to define factors that can stimulate
      growth and differentiation of bone marrow (BM) derived progenitor cells. These
      growth factors for hematopoiesis were termed Colony Stimulating Factors (CSFs)
      since the assay system was to induce colonies. With the application of molecular
      biologic approaches, the genes encoding for these CSFs have been localized and
      cloned. Production of CSFs and other soluble signal substances (cytokines) as
      pure proteins have led to important insights into how hematopoiesis is regulated
      by a complex network made up by interactions between cells and cytokines. The
      availability of CSFs in clinically useful amounts has also led to clinical trials
      with new strategies for treating hematopoietic dysfunctions, congenital or
      acquired. Because others have recently reviewed clinical applications or basic
      science studies on the colony stimulating factors, we will summarize the two with
      focus on common features between the different CSFs.

PMID- 8258996
TI  - Strategies for cytokine utilisation in tumor therapy.
AB  - The state of the art with regard to the employment of various cytokine-based
      tumor immunotherapy strategies and their mechanisms of action are critically
      reviewed. As matters now stand, adoptive transfer of LAK cells or tumor
      infiltrating lymphocytes together with high doses of IL-2 constitutes the only
      immunologic way to hinder tumor growth in advanced stages of cancer. On the other
      hand, many experimental data show that the local presence of cytokines, either
      injected repeatedly at tumor site or released by cytokine-gene engineered tumor
      cells, arouses immunogenicity in apparently nonimmunogenic spontaneous tumors. By
      strengthening the notion that most tumors are potentially immunogenic, these
      findings offer substantial evidence to stress the potential use of cytokines as a
      component of new tumor vaccines.

PMID- 8258997
TI  - The therapeutic use of the unconjugated monoclonal antibodies (MAb) 17-1A in
      combination with GM-CSF in the treatment of colorectal carcinoma (CRC).
AB  - Unconjugated monoclonal antibodies (MAb) and granulocyte macrophage-colony
      stimulating factor (GM-CSF) may induce tumor regression in patients. Antibody
      dependent cellular cytotoxicity (ADCC) is considered to be one of the effector
      functions of MAb. Human peripheral blood mononuclear cells (PBMC) preincubated
      with GM-CSF and used as effector cells in an 18h ADCC assay with SW948 (human
      colorectal carcinoma cell line) as target cells and MAb 17-1A induced significant
      increase in the lytic capacity of the effector cells. Based on these findings the
      therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) against
      colorectal carcinoma (CRC) cells and GM-CSF was evaluated in 20 patients with
      metastatic CRC. The patients received GM-CSF (250 micrograms/m2/day s.c.) for 10
      days and a single i.v. infusion of MAb 17-1A (400 mg) at day 3 of the cycle. The
      cycles were repeated with an interval of one month. Four cycles were given. ADCC
      as well as Fc-receptor bearing mononuclear cells increased significantly during
      therapy. Two patients achieved CR (10%). One patient had an MR (5%) and a further
      three patients were considered to have SD > 3 months (15%). The two CR patients
      are still in CR, 35+ and 30+ months respectively after initiation of therapy.
      Patients with an ADCC activity at start of therapy above the median value of the
      total patient material survived significantly longer than those patients with an
      ADCC reactivity below this value (p = 0.002).

PMID- 8258998
TI  - The 5-HT4 receptor.

PMID- 8258999
TI  - Beta 3 and atypical beta-adrenoceptors.

PMID- 8259000
TI  - Inhibitors of aspartyl proteinases.

PMID- 8259001
TI  - [Our new fragile world doesn't consist of developed and developing countries
      only].

PMID- 8259002
TI  - [SOS directions on quality assurance: a paradigmatic shift in Swedish health
      care].

PMID- 8259003
TI  - [The family practice reform--for better or worse?].

PMID- 8259004
TI  - [The drug committees will play a key role].

PMID- 8259005
TI  - [Changing rehabilitation. New methods and new challenges].

PMID- 8259006
TI  - [The PCR method and directed mutagenesis. What significance do discoveries by
      chemistry Nobel Prize winners have for medicine?].

PMID- 8259007
TI  - [Negative effects of the labour-market. Rehabilitation on the rise].

PMID- 8259008
TI  - [Social rehabilitation of patients with coronary disease. A new form of
      cooperation improves results].

PMID- 8259009
TI  - [Phimosis--an overestimated problem? Circumcision of young boys is being
      performed much too frequently].

PMID- 8259010
TI  - [Genital papillomavirus infection. A diagnostic and therapeutic dilemma].

PMID- 8259011
TI  - [Anorexia nervosa. Anemia of our time].

PMID- 8259012
TI  - [Smallpox and fertility. A new study of old material].

PMID- 8259013
TI  - [The disease is eradicated but... should we destroy the smallpox virus species?].

PMID- 8259014
TI  - [Medical quality indicators. A suggestion on taxonomy].

PMID- 8259015
TI  - [Early warning concerning several cases of side effects associated with
      remoxipride].

PMID- 8259016
TI  - [Competition based on equal conditions--does it exist in the health care field?].

PMID- 8259017
TI  - [Priorities in health care].

PMID- 8259018
TI  - [Harmony in physician-patient relation--it does exist!].

PMID- 8259019
TI  - [Routine surgery is superior to percutaneous diskectomy].

PMID- 8259020
TI  - [Does metabolic rate slow down after smoking cessation?].

PMID- 8259021
TI  - [Non-Scandinavian physicians--a group of low priority].

PMID- 8259022
TI  - [Cancer in situ is not "cancer"].

PMID- 8259023
TI  - [Competition means high quality].

PMID- 8259024
TI  - [Hyperandrogenism or insulin resistance. What is the cause and effect in diabetes
      among women?].

PMID- 8259025
TI  - [Capacity of the elderly and demands of work].

PMID- 8259026
TI  - [Rehabilitation in a geriatric perspective. New approach, new way of working].

PMID- 8259027
TI  - [Reconstruction of the lower urinary tract. New continent methods].

PMID- 8259028
TI  - [Increased significance of integrative physiology--especially in the age of
      molecular biology].

PMID- 8259029
TI  - [Smooth start in life reduces the scars from stress? The brain in focus of a new
      health care trend].

PMID- 8259030
TI  - [Sudden death among orienteerers. Disseminated histopathological findings
      surprise the scientists].

PMID- 8259031
TI  - [Unusual infectious complication in a pregnant woman. Spontaneous abortion caused
      by Campylobacter coli].

PMID- 8259033
TI  - [Freedom of choice and monopoly. When "my" patient goes to others].

PMID- 8259032
TI  - [A case report. Mirror movements in Kallmann syndrome].

PMID- 8259034
TI  - Total therapeutic paracentesis (TTP) with and without intravenous albumin in the
      treatment of cirrhotic tense ascites: a randomized controlled trial.
AB  - We studied 35 cirrhotic patients with tense ascites assigned at random into two
      groups: Group I consisted of 17 patients treated by total therapeutic
      paracentesis (TTP) (6-15 l) plus i.v. albumin (5 g/l of fluid) and Group II
      consisted of 18 patients treated by TTP (5.5-15.5 l) without albumin. On 19
      patients we performed a sequential assessment of cardiac output (CO), plasma
      renin activity (PRA) and plasma aldosterone (PA). Both groups were similar in
      age, sex, and etiology of cirrhosis. CO, PRA and PA values were expressed as mean
      changes occurring in relation to their respective baseline values. CO changes
      after TTP (l/min): Group I: 2.5 after 6 h and 2.2 after 12 h; Group II: 2.2 after
      6 h and -0.4 after 12 h, (p < 0.05 comparing values after 12 h between the two
      groups). PRA changes after TTP (ng/dl/h): Group I: -7.4 after 1 h, -7.8 after 6 h
      and -3.2 after 24 h; Group II: -2.4 after 1 h, -0.8 after 6 h and 3.9 after 24 h
      (p < 0.05 comparing values between both groups after 6 and 24 h). PA changes
      after TTP (ng/dl): Group I: -50.5 after 1 h, -36.7 after 6 h and -34.6 after 24
      h; Group II: -18.2 after 1 h, -2.2 after 6 h and 20 after 24 h, (p < 0.05
      comparing values between both groups after 1 and 6 h). Complications were minimal
      in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259035
TI  - Human hepatic infarction: histopathological and postmortem angiological studies.
AB  - Twenty hepatic infarction cases selected from 5420 consecutive autopsy cases were
      investigated to clarify the pathogenetic aspects of this disease. Additional
      postmortem angiological studies of 24 normal human livers obtained at autopsy
      were also further performed to analyse the effects of blocking vascular
      structures on lesion development. Seventeen of the 20 cases (85%) were clinically
      associated with systemic circulatory insufficiency, especially hepato- and/or
      renal failure. Histopathologically, there was a significantly closer relationship
      between the location of infarcted regions and portal vein thrombosis than with
      either hepatic vein thrombosis or hepatic arterial damage. The borders between
      infarcted regions and surviving hepatic parenchyma were located around central
      veins, corresponding with the microcirculatory periphery of the portal venous
      system. Postmortem angiographic studies revealed that hepatic lobuli mainly
      consist of portal vein branches. Moreover, postmortem embolization studies of six
      normal livers using glass beads and barium-gelatin injection showed that physical
      occlusion of portal vein branches produced defects in broad areas of the hepatic
      parenchyma. Therefore, it is suggested that the development of hepatic infarction
      principally depends on disturbances of the portal venous system. In addition,
      systemic circulatory insufficiency, which reduces the intrahepatic blood flow,
      probably contributes greatly to the development of hepatic infarction.

PMID- 8259036
TI  - Bile and plasma lipid composition in non-obese normolipidemic subjects with and
      without cholesterol gallstones.
AB  - A two-stage study was carried out to characterize the bile and plasma lipid
      composition in normolipidemic non-obese patients with and without cholesterol
      gallstones. The first stage involved 11 patients with cholesterol gallstones
      admitted for elective cholecystectomy and a control group of 16 patients without
      cholesterol gallstones undergoing elective laparotomy. Bile samples were obtained
      intraoperatively by aspiration from the gallbladder. The bile of all the
      gallstone patients was supersaturated with cholesterol and its nucleation time
      was much shorter than that of bile in the control group (2.5 days vs 22.5 days,
      respectively, P < 0.001). The biliary fatty acid profile of phosphatidylcholine
      (PC) and free fatty acids (FFA) of gallstone patients was similar to that of the
      control group. C-22 fatty acids were found in a higher concentration in the FFA
      than in the PC fatty acids (P < 0.05) in both groups of patients. Plasma
      triglyceride levels in the gallstone patients were significantly higher than
      those in the control group and the biliary cholesterol level correlated with that
      of plasma triglycerides. In the second stage of the study, plasma lipid profiles
      were obtained in two additional groups of patients, 20 patients with and 24
      patients without cholesterol gallstones, for an in-depth characterization of the
      differences in plasma lipid profiles. The gallstone patients were found to have
      not only significantly higher concentrations of plasma triglycerides but
      increased cholesterol and phospholipid level as well. These differences were
      essentially due to a higher lipid content of the plasma VLDL fraction, similar to
      the pattern of patients with type IV hyperlipoproteinemia.

PMID- 8259037
TI  - Changes of serum 2',5'-oligoadenylate synthetase activity during interferon
      treatment of chronic hepatitis C.
AB  - It was our aim to evaluate whether the baseline activity of 2-5 oligoadenylate
      synthetase (2-5 OAS) in serum and changes induced by the treatment with
      interferon are relevant factors in remission of chronic hepatitis C. Seventeen
      out of 30 adult patients with chronic hepatitis C were randomized to receive
      recombinant alpha-2b interferon at the dosage of 3 MU three times weekly. By the
      end of the third month, nine patients had normalized transaminase levels and
      continued to receive 3 MU of interferon for an additional 3 months, whereas in
      eight non-responders the dosage was increased to 6 MU for the same period of
      time. A single patient responded to the increased dosage. Baseline 2-5 OAS serum
      activity was significantly higher in patients with chronic hepatitis when
      compared with normal controls. Follow-up on the 13 untreated cases showed that 2
      5 OAS elevation was stable and unrelated to concomitant infections. Comparison of
      responders and non-responders showed that the latter had higher baseline 2-5 OAS
      activity, tended to have an earlier and higher peak in the enzyme during the
      first 4 weeks of treatment, and maintained higher levels during the first 3
      months of therapy. The increased dosage of interferon in this group led to an
      additional, although temporary, increase in 2-5 OAS. Our data suggest that HCV
      infection by itself induces elevated 2-5 OAS levels. The paradoxical increase in
      non-responders indicates that monitoring of the enzyme in serum does not predict
      the response to interferon. The role of the 2-5 OAS pathway in inducing the
      antiviral state in HCV infection should be further evaluated at tissue level.

PMID- 8259038
TI  - Low frequency of allelic loss in the cyclin A gene in human hepatocellular
      carcinomas: a study based on PCR.
AB  - The cyclin A gene was first identified at a site of hepatitis B virus DNA
      integration in a primary liver cancer (PLC). It has now been mapped to 4q27, in
      the proximity of a chromosomal locus (4q32) which is frequently rearranged and
      deleted in PLC. We took advantage of the TaqI polymorphism recently described in
      the cyclin A gene to search for allelic loss in this gene by means of PCR.
      Tumorous and non-tumorous tissue from 50 patients with PLC was analyzed: 27
      samples (54%) were homozygous for the A1 type allele (i.e. the allele bearing the
      TaqI restriction site), three (6%) were homozygous for the A2 type allele
      (without the TaqI site) and 20 (40%) were heterozygous. Comparison of tumorous
      and non-tumorous patterns showed that only one (5%) tumorous tissue out of 20
      heterozygous patients was homozygous, indicating the loss of an allele at this
      locus. We conclude that allelic loss in the cyclin A gene is a rare event in
      patients with PLC, and that PCR is rapid and reliable for the detection of
      allelic loss in the cyclin A gene when only small amounts of DNA are available.

PMID- 8259039
TI  - Taurine conjugate of ursodeoxycholate plays a major role in the hepatoprotective
      effect against cholestasis induced by taurochenodeoxycholate in rats.
AB  - Rats which were taurine-deprived through beta-alanine administration and
      untreated rats were used to elucidate the mechanism of hepatoprotective effects
      of ursodeoxycholate (UDC). Animals were infused with taurochenodeoxycholate
      (TCDC, 0.4 mumol.min-1.100 g-1) alone or in combination with
      tauroursodeoxycholate (TUDC), or with UDC (both 0.6 mumol.min-1.100 g-1) for 2 h.
      Ursodeoxycholate as well as TUDC prevented severe cholestasis and liver damage
      induced by TCDC infusion in both untreated and taurine-deprived rat groups. In
      untreated rats, however, UDC was less effective in hepatoprotection than TUDC as
      indicated by sequential changes in biliary LDH output during the period of 30 to
      120 min (P < 0.05). In rats receiving UDC and TCDC, total biliary output of LDH
      for 2 h was significantly higher in taurine-deprived rats than that in the
      control (73.40 +/- 10.10 vs 41.14 +/- 12.56: P < 0.05), suggesting that the
      difference became greater upon taurine deprivation. In contrast, in rats
      receiving TUDC and TCDC, the protective effect was comparable for the taurine
      deprived and untreated rats. When the animals were infused with UDC and TCDC,
      taurine-deprived rats exhibited a biliary excretion rate for TUDC half that of
      control rats (P < 0.05). Furthermore, a highly significant correlation was
      observed between the biliary excretion rate of TUDC and biliary output of LDH (r
      = -0.886, P < 0.0001). These results suggest that UDC conjugates, especially
      TUDC, and not UDC may play a major role in the prevention of cholestasis and
      liver cell damage caused by TCDC infusion.

PMID- 8259040
TI  - Fine-needle liver biopsy in patients with severely impaired coagulation.
AB  - Severe coagulation defects, as reflected by platelet count and prothrombin time,
      have always been considered a contraindication to needle biopsy of the liver, but
      there are very limited data on the actual rate of bleeding in patients with such
      severe alterations and none whatsoever on the bleeding risk associated with
      newer, fine-gauge needles that produce less trauma to the liver tissue. In
      addition, there has never been any evidence that platelet count and/or
      prothrombin time are the most sensitive indices of bleeding risk. This
      retrospective study of 85 patients, with platelet counts less than 50,000/mm3
      and/or prothrombin times less than 50% of controls, subjected to ultrasound
      guided fine-needle liver punctures for diagnostic or therapeutic (percutaneous
      ethanol injection) purposes showed no bleeding episodes after any of the 229
      punctures performed. No type of replacement therapy was administered to correct
      clotting defects prior to the procedure. Correct pathologic diagnoses were
      obtained in 81.2% of all patients. Ultrasound-guided fine needle puncture appears
      to be safer than currently believed in patients with severe clotting defects and
      deserves further evaluation as an alternative to surgical procedures to diagnose
      and treat liver lesions, even when severe coagulation impairment is present.

PMID- 8259041
TI  - The mutation of codon 249 in the p53 gene is not specific in Japanese
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma samples obtained from 59 patients at surgical resection
      were examined for mutations of the third base at codon 249 of the p53 gene, using
      the polymerase chain reaction and oligonucleotide hybridization techniques. This
      point mutation, which is frequently observed in HCC cases from Southern Africa
      and Quidong in China, was not recognized in either 60 hepatocellular carcinomas
      or 53 noncancerous liver tissue samples from Japan. Thirty-four of 45 patients
      (75.6%) were positive for the hepatitis C virus, which was a higher rate than
      that for hepatitis B virus infection (9 of 55; 16.4%). The exposure to aflatoxin
      B1 was not considered to be remarkable. These results suggest that the point
      mutation of the third base at codon 249 is not common in Japanese patients, and
      it is suggested that numerous other factors affect the mutation of the p53 gene
      and the development of hepatocellular carcinoma.

PMID- 8259042
TI  - Role of hepatic vitamin A and lipocyte distribution in experimental hepatic
      fibrosis.
AB  - Lipocytes are the major site of hepatic vitamin A storage, and they have been
      demonstrated to lose their vitamin A content in the process of hepatic fibrosis.
      To investigate the relationship between hepatic vitamin A content and the degree
      of hepatic fibrosis, we measured levels of retinyl palmitate and retinol in the
      CCl4-induced fibrotic liver using high-performance liquid chromatography. We
      estimated hepatic collagen content using a spectrophotometric analysis with
      sirius red, and also by measuring hydroxyproline levels. Lipocytes were detected
      by an immunoperoxidase method with anti-desmin antibody, and were counted
      morphometrically through a Texture Analyzing System. A significant negative
      correlation was observed between the level of retinyl palmitate and collagen
      content (r = -0.64) as well as the hydroxyproline level (r = -0.69) in the CCl4
      induced fibrotic liver. In the process of fibrosis, hepatic retinol levels were
      elevated in association with a decrease in retinyl palmitate. In particular in
      the early stage of fibrosis, lipocytes increased remarkably in number in fibrotic
      areas in spite of a decrease in total hepatic vitamin A. The present study
      suggests that an increase in hepatic retinol as well as a decrease in retinyl
      palmitate may facilitate the process of hepatic fibrosis produced by lipocytes.

PMID- 8259043
TI  - Infection in major sickle hemoglobinopathies: should management strategies
      change?
AB  - Four children with major sickle hemoglobinopathies developed severe pneumococcal
      infection. Three had sickle cell hemoglobin C (Hb SC) disease and one had sickle
      cell anemia (Hb SS). In three instances, there was a fatal outcome. The authors'
      experience with these cases leads them to question whether any patient with a
      major sickle hemoglobinopathy should be excluded from receiving prophylactic
      penicillin or if outpatient management with long-acting cephalosporin treatment
      in the sickle cell patient with suspected sepsis is appropriate therapy.

PMID- 8259044
TI  - Hypokalemia associated with ticarcillin-clavulanic acid.
AB  - Charts of 16 patients on ticarcillin-clavulanic acid were examined. Eight
      patients were found to have hypokalemia, yet not all were screened routinely for
      potassium imbalance. Some physicians prescribing ticarcillin-clavulanic acid seem
      unaware of the drug's side effect.

PMID- 8259046
TI  - Med Chi launches a major family violence prevention initiative.

PMID- 8259045
TI  - Vignette of medical history: porphyria in royalty.
AB  - The porphyrias are a group of uncommon inherited disorders caused by an
      accumulation of porphyrins in the body. This paper identifies many of the
      individuals in the royal houses of Stuart, Hanover, and Prussia who were
      afflicted with this condition, and highlights the impact this disease had on the
      history of England.

PMID- 8259047
TI  - Needle aspiration cytologic biopsies of breast masses--economical and accurate.

PMID- 8259048
TI  - Cost-effectiveness questioned.

PMID- 8259049
TI  - Tuberculosis: optimism, pessimism, frustration.
AB  - The re-emergence of tuberculosis as a serious public health threat has captured
      the nation's attention. Tuberculosis more frequently affects the ethnic
      minorities and the socially and economically disadvantaged residents of Maryland.
      Effective regimens are available to treat and prevent tuberculosis. Consistent
      application of proven infection control measures and of treatment and prevention
      regimens will prevent the development and spread of multidrug-resistant
      tuberculosis.

PMID- 8259050
TI  - Substance abuse as a factor in the causality, severity, and recurrence rate of
      traumatic brain injury.
AB  - The effects of substance abuse on the cause, severity, and recurrence of
      traumatic brain injury in 322 admissions to a large rehabilitation inpatient
      facility are explored. Study patients tended to be young and predominantly male.
      Few had completed high school and a significant minority had a history of
      cerebral dysfunction. Patients tended to have moderate to severe closed head
      injuries. Motor vehicle crashes were the most common cause of injury, but
      patients reporting drug or drug and alcohol abuse were more likely to sustain
      violent injuries (e.g., gunshot wounds).

PMID- 8259051
TI  - Characteristics of epidemic hepatitis A in Baltimore City: implications for
      control measures.
AB  - In 1988, a hepatitis A epidemic began in Baltimore, Maryland. A total of 607
      cases were reported to the Baltimore City Health Department between the period
      November 1, 1988, and December 31, 1989. The health department conducted case
      investigations to identify factors important to the development of control
      measures. Immunoglobulin was given to appropriate contacts, and an educational
      campaign was initiated. Of the 607 reported cases, 63% were white and 57% were
      male. Cases were geographically clustered within 5 of Baltimore's 23 zip codes.
      Among the 242 adults interviewed, 43% self-reported drug use and 44% were
      unemployed. Twenty-one percent of the adults and 56% of the children reported
      contact with either a suspected or confirmed case of hepatitis. Despite control
      efforts, the epidemic continued through 1990. Barriers to implementing
      traditional control measures resulted in continuing transmission of hepatitis A
      in the community.

PMID- 8259053
TI  - Migration and biodegradation of free silicone from silicone gel-filled implants
      after long-term implantation.
AB  - In vivo 1H NMR chemical shift imaging (CSI), 1H NMR localized spectroscopy
      (STEAM) and multinuclear NMR spectroscopy (29Si, 13C, 1H) were used to
      characterize the aging process of silicone gel-filled implants in a rat model
      after long-term implantation. Although no significant changes could be observed
      in the implants or surrounding tissue by in vivo 1H chemical shift imaging, in
      vivo 1H localized spectroscopy of the livers from the longer term population
      revealed the presence of silicone. Ex vivo 29Si spectroscopy of the liver,
      spleen, and the capsule formed around the 9 and 12 month implants clearly
      demonstrated and confirmed for the first time that a significant amount of free
      silicone migrates from silicone gel-filled implants. Also, these results show
      that silicones are not metabolically inert, and their biodegradation in tissue
      and within the implant can be monitored after 9 and 12 months by changes in the
      29Si chemical shifts seen in corresponding ex vivo spectra. The NMR findings are
      supported by those obtained by atomic absorption spectroscopy. Silicone aging
      changes not only the chemical composition of the gel, but also its proton T2
      relaxation times, which increase with long implantation times. The three
      dimensional structure of the gel disintegrates (i.e., polymer chain rupture),
      increasing the molecular mobility of the polymer and, consequently, its protons
      T2 values. The relaxation data we obtained reflect this in vivo degradation,
      especially in the case of implant rupture. Additionally, small concentrations of
      fat in the silicone gel were found within the implants. The presence of these
      lipophilic substances also might increase the T2 values (plasticizer effect).
      These findings may assist in evaluating the implant integrity and disease
      symptoms related to their presence in humans.

PMID- 8259052
TI  - Assessment of human colorectal biopsies by 1H MRS: correlation with
      histopathology.
AB  - Samples (3 mm3) of histopathologically normal (n = 15) and carcinomatous tissue
      (n = 15) were obtained from colectomy specimens and examined by 1H MRS. A
      combination of one- and two-dimensional spectra, obtained with appropriate
      acquisition and processing parameters, provide multiple diagnostic parameters
      allowing the distinction between normal and carcinomatous tissue. The diagnostic
      parameters include resonances from choline, choline-based, and other metabolites,
      cell surface fucosylation, and altered lipid profiles. Tissues
      histopathologically classified as normal, while remaining distinct from the
      malignant spectral profile, were found to fit into two categories, one of which
      had some of the spectral characteristics of malignancy. These results indicate
      that 1H MRS identifies abnormal colorectal mucosa, which is not morphologically
      manifest. Such abnormalities have been reported previously to exist in
      premalignant colorectal tissue by monoclonal antibody studies. Collectively,
      these results suggest that a clinical study of colorectal biopsies by 1H MRS
      could provide support for the use of MRS as an adjunct to current pathological
      procedures.

PMID- 8259054
TI  - In vivo proton spectroscopy and spectroscopic imaging of [1-13C]-glucose and its
      metabolic products.
AB  - Metabolism of [1-13C]-glucose was studied in situ in cat brain using gradient
      enhanced proton-detected heteronuclear spectroscopy. Proton detection of [1-13C]
      glucose, [3-13C]-lactate, 4-[13C]-glutamine, 4-[13C]-glutamate and the combined
      signals 2-[13C]-glutamate/glutamine and 3-[13C]-glutamate/glutamine was achieved,
      despite the fact that some of the associated proton resonances are close to the
      water signal. Two-dimensional [1H-13C]-spectra demonstrate the possibility of in
      situ spectral assignment with 1H sensitivity and 13C resolution. Spectroscopic
      images of glucose and its metabolic products were also acquired, showing the
      possibility to study spatial dependence of metabolism.

PMID- 8259055
TI  - Comparison of methods for the determination of absolute metabolite concentrations
      in human muscles by 31P MRS.
AB  - In order to determine metabolite concentrations in human skeletal muscles by in
      vivo 31P MRS, different quantification methods were analyzed with regard to the
      accuracy and reproducibility of results and the simplicity of handling. Each
      quantification method comprised a calibration strategy and a localization
      technique. Extensive in vivo and in vitro tests showed that homonuclear phantom
      based calibration strategies yielded significantly more accurate (lower
      systematic errors) and more reproducible (lower statistical errors) concentration
      estimates than heteronuclear strategies using internal water as a concentration
      standard. Additionally, the former strategies are easier to handle than the
      latter. Localization with the volume-selective sequence ISIS yielded slightly
      more reproducible results than localization by surface coil. We conclude that
      phosphorus metabolite concentrations are determined most accurately with phantom
      based calibration strategies in combination with ISIS localization (measurement
      errors approximately 5-7%).

PMID- 8259056
TI  - Oxygen tension in a murine tumor: a combined EPR and MRI study.
AB  - The effects of fusinite, a new agent for the measurement of the concentration of
      oxygen in vivo by EPR, on MRI images have been studied. There was little effect
      on spin-echo T1-weighted images, but the fusinite resulted in large effects on T2
      weighted images. Especially large effects could be observed when using spoiled
      gradient echo sequences (SPGR). The observed measurements of oxygen by EPR
      corresponded to the relative vascularity at the site of the fusinite both
      histologically and by MRI studies of vascularity using Gd-DTPA as a contrast
      agent. We conclude that by using the effects of fusinite on magnetic
      susceptibility, it can be located accurately and noninvasively with MRI and
      thereby the value of the use of fusinite to measure concentration of oxygen in
      vivo is enhanced.

PMID- 8259057
TI  - The use of dietary loading of 133Cs as a potassium substitute in NMR studies of
      tissues.
AB  - 133Cs NMR chemical shifts and relaxation times have been measured for tissue
      samples in vitro and in vivo from rats which have been fed on a high cesium, low
      potassium diet, which leads to a predominantly intracellular distribution of this
      ion, similar to that of K+. The high sensitivity, large chemical shift range, and
      narrow linewidths of 133Cs, compared with 39K, allow chemical shift differences
      to be observed between tissues, and in subcellular organelles such as
      mitochondria. For example, in vitro tissue chemical shifts, relative to 150 mM
      CsCl, are 1.06 +/- 0.11 ppm for liver, 0.02 +/- 0.05 ppm for brain, 1.76 +/- 0.20
      ppm for erythrocytes, and -0.13 +/- 0.02 ppm for plasma. T1 and spin-echo T2
      values range from 1.26 +/- 0.05 s (T1), and 0.028 +/- 0.006 s (T2) for liver, to
      6.49 +/- 0.19 s and 1.12 +/- 0.03 s for plasma. 133Cs relaxation times show the
      same relative trends between tissues as are observed in 39K tissue studies.

PMID- 8259058
TI  - Gd(DOTP)5-outer-sphere relaxation enhancement promoted by nitrogen bases.
AB  - The relaxation properties of Gd(DOTP)5- (1, 4, 7, 10-tetra-azacyclododecane-
      N,N',N'',N'''-tetrakis(methylenephosphonic acid)) have been investigated as a
      function of pH, temperature, concentration, and magnetic field strength. We have
      found that the complex has one exchangeable water molecule in its inner
      coordination sphere, at a distance of 3.26 A from the metal ion, and it does not
      form oligomers in solution in the concentration range 0.2 to 10 mM. The possible
      presence of two species in solution with an average fractional hydration number
      is also taken into accounts. The NMRD profiles were recorded at 5 degrees C, 25
      degrees C, and 35 degrees C and quantitatively analyzed in terms of the
      paramagnetic relaxation equations. Interestingly the addition to a solution of
      the Gd(III)-complex of nitrogen bases results in a marked relaxation enhancement,
      which shows a strong pH dependence with a maximum around pH = 9. The relaxivity
      gain has been shown to depend on outer-sphere effects originating from multiple
      electrostatic interactions between the anionic complex and the organic cations
      that bring the exchangeable protons of the substrate molecules in to close
      proximity with the paramagnetic center. High resolution NMR relaxation data for N
      methyl-D(-)-glucamine suggest that the hydroxyl group on the beta-carbon plays a
      role in stabilizing the interaction, presumably through a hydrogen bond with an
      uncoordinated oxygen atom of the complex.

PMID- 8259059
TI  - Evaluation of a nitroxyl fatty acid as liver contrast agent for magnetic
      resonance imaging.
AB  - In this study, we report the synthesis and the evaluation as MRI contrast agent
      of a new compound (nitroxyl fatty acid, NFA), where a pyrrolidinoxyl radical (3
      carboxy-proxyl, PCA) is linked to a fatty acid moiety. Fatty acids were selected
      as vector because they present a high affinity for the liver, their efficient
      cellular uptake being the result of a specific interaction with a transmembrane
      transporter (liver plasma membrane-fatty acid binding protein). The uptake of 3H
      oleic acid is inhibited after the injection of 1 mmol/kg of NFA, suggesting that
      NFA recognizes the same transmembrane transporter as the natural fatty acids. The
      higher relaxivity R1 of NFA in albumin solutions, compared with PCA, was
      explained by the immobilization of the nitroxyl radical in the protein. MR
      imaging was performed using T1-weighted images on mice in order to compare the
      contrast effect obtained after the injection of 1 mmol/kg of radical. The %
      signal enhancement in the liver 5 min after intravenous injection was 49 +/- 4
      and 14 +/- 5 for NFA and PCA, respectively. NFA allowed a better delimitation of
      some necrotic tumors (Novikoff hepatocarcinoma) due to its preferential uptake by
      the nontumorous tissue.

PMID- 8259060
TI  - Generalized matched filtering for time-resolved MR angiography of pulsatile flow.
AB  - Generating flow-specific images (arteriograms, venograms) with optimal signal-to
      noise ratios for time-resolved MR angiography is a conditional maximum problem,
      and its solutions are generalized matched filters. We have investigated six
      matched filters, corresponding to all possible combinations of three flow
      suppression conditions and two signal-to-noise ratio maximization procedures.
      Four of these matched filters correspond to previously described methods: the
      subtractive matched filter, the standard deviation, the global venous eigenimage
      and the global arterial eigenimage. The two others are referred to here as the
      local venous eigenimage and the local arterial eigenimage. These six matched
      filters have been applied to 2D time-resolved phase contrast angiographic data.
      The local arterial eigenimage is found to be the most effective in suppressing
      undesired venous flow and preserving desired arterial flow.

PMID- 8259061
TI  - Ultrafast interleaved gradient-echo-planar imaging on a standard scanner.
AB  - Ultra-fast imaging traditionally implies either echo-planar imaging on specially
      developed gradient systems, or very short repetition time gradient-echo imaging
      on standard magnetic resonance imaging scanners. An alternative strategy for very
      fast imaging with conventional whole-body scanners is discussed here. The
      technique is a hybrid, whereby the advantages of gradient-echo imaging and echo
      planar imaging are combined. It is here denoted interleaved gradient-echo-planar
      imaging. It is not a single specific measurement sequence, but rather a continuum
      of sequences whereby multiple excitations with multiple gradient-echos are
      employed. The power of this fast imaging approach is that one has much more
      flexibility toward the optimization of the measurement sequence with respect to
      imaging time, T2 relaxation, gradient power, resolution, image distortion, and
      signal-to-noise ratio. In vivo human heart images, acquired in 110 ms, and with a
      resolution of 2.5 mm, have been obtained with a standard whole-body scanner.

PMID- 8259062
TI  - Intracellular labeling of T-cells with superparamagnetic contrast agents.
AB  - Isolated rat T-cells have been labeled intracellularly, using endocytosis uptake
      of two superparamagnetic contrast agents, AquaMag100 and BMS180549, which are
      both iron-oxide particles coated with dextran. No deterioration of cell
      proliferation response to mitogen stimulation was observed after labeling with
      either superparamagnetic contrast agent. AquaMag100 particles show aggregation
      and co-precipitation in culture media for T-cells. BMS180549 particles not only
      produce no observable aggregation or co-precipitation, but also have a higher
      efficiency for labeling T-cells than AquaMag100. The efficiency of cell labeling
      was determined by measuring the decrease in the spin-spin relaxation time of the
      water proton in cell samples containing 1 x 10(7) labeled T-cells/milliliter of
      2% w/w gelatin. After optimization of the labeling procedures, a shortening of
      the spin-spin relaxation time by a factor of approximately 7 to 10 has been
      demonstrated. Under the present experimental conditions, the up-regulation of low
      density lipoprotein receptor does not increase the labeling efficiency by
      endocytosis. Our results suggest that intracellular labeling of specific cell
      types can be achieved with good efficiency and the labeled cells can be detected
      by magnetic resonance imaging in rat testicles in vivo.

PMID- 8259063
TI  - A comparison of an inductively coupled implanted coil with optimized surface
      coils for in vivo NMR imaging of the spinal cord.
AB  - A study was performed to determine whether an implanted, inductively coupled
      nuclear magnetic resonance (NMR) imaging spine coil could provide a significant
      gain in signal-to-noise ratio (SNR) on images of the spinal cord relative to the
      SNR of optimized surface coils. Implanted coils were surgically affixed to the
      upper lumbar spine (first lumbar through third lumbar vertebrae) in a total of
      four adult cats. The implanted coil was inductively coupled to an external 12 x
      12 cm square surface coil that was mounted on a 14-cm diameter Plexiglas cradle
      (Townsend Industries, Des Moines, IA). Two similar cradles were prepared with
      transmit-only 12 x 12 cm surface coils and either a receive-only 6 x 6 cm square
      surface coil or a receive-only quadrature coil pair (two 4 x 6 cm coils
      overlapped slightly to minimize their mutual inductance) with the same surface
      area (6 x 6 cm). A total of five single-slice, T1-weighted spin-echo images (TR =
      500 ms, TE = 30 ms, 4-mm slice thickness) were acquired from a 1-liter saline
      phantom and from the second lumbar spinal level in an adult cat with a normal,
      uninjured spinal cord. On the spinal cord images, the quadrature coil exhibited a
      factor of 1.65 increase in SNR relative to the single-turn surface coil, whereas
      the implanted coil achieved a factor of 2.19 increase in SNR. The improved SNR
      for the quadrature and implanted coils was observed as a dramatic improvement in
      the clarity of the images.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259064
TI  - Experimental design of 31P MRS assessment of human forearm muscle function:
      restrictions imposed by functional anatomy.
AB  - The restrictions imposed by the functional anatomy of the finger flexor muscles
      on the experimental design of 31P MRS assessment of human forearm muscle function
      employing surface coil localization and voluntary exercise were investigated. It
      was found that 31P MRS metabolic data of finger flexor muscle should be
      correlated with mechanical data of combined flexion of only the ring and little
      fingers, rather than all four fingers as has been commonly the case in previously
      reported studies.

PMID- 8259065
TI  - Fast proton spectroscopic imaging using the sliced k-space method.
AB  - The use of one-shot imaging methods for proton spectroscopic imaging (1H-SI) is
      examined. In particular the acquisition of Kx x Ky x Nt data points by means of
      Nt excitations, each acquiring a Kx x Ky k-space slice, is advocated. A number of
      strategies for realising this experiment, and combining it with water suppression
      and volume-selection are proposed. The practical implementation at 4.7 T for 1H
      SI of the rat brain is described. Experimental results from a 32 x 32 spatial
      matrix with Nt = 64 are presented. Spectra obtained from volumes as low as 3.5
      microliters and within measuring times of as little as 3.8 min are shown. In
      these choline, creatine/phosphocreatine and N-acetylaspartate are all clearly
      visible.

PMID- 8259066
TI  - A potentially artifact-free oral contrast agent for gastrointestinal MRI.
AB  - The combination of diamagnetic barium sulfate and superparamagnetic iron oxide
      (SPIO) in one suspension produces a macroscopic cancellation of positive and
      negative magnetic susceptibility components that can potentially eliminate
      susceptibility artifacts even with gradient echo pulse sequences. The relaxation
      properties that make the SPIO suspension a useful negative contrast agent are
      retained.

PMID- 8259067
TI  - Imaging of human brain activity at 0.15 T using fluid attenuated inversion
      recovery (FLAIR) pulse sequences.
AB  - A 3-4% change in signal intensity correlated with visual stimulation was observed
      in the occipital lobes of three normal volunteers examined with MRI at 0.15 T
      using fluid attenuated inversion recovery pulse sequences. Similar results were
      observed at 1.0 T. A double difference technique in which difference images are
      themselves opposed provided an increase in sensitivity.

PMID- 8259068
TI  - Excessive water drinking and cataract formation: a case report.
AB  - We report a case of a 46-year-old man who developed mature cataract in one eye
      and nearly mature cataract in his other eye over a 14-month period. No genetic,
      traumatic, or toxic etiology or intraocular pathology or history of irradiation
      were present. The patient had intentionally been drinking 15 liters of water a
      day for 11 months, up until 3 months prior to his admission, and 5 liters a day
      thereafter, until his admission. During his hospitalization he was found to
      suffer from insulin-dependent diabetes mellitus. The rest of his medical work-up
      was found to be normal. We suggest that the huge water overload put on his lens
      played a role in the premature and rapid cataract formation.

PMID- 8259069
TI  - Isolated homonymous lateral hemianopsia revealing central nervous system
      toxoplasmosis as the initial manifestation of AIDS.
AB  - A 25-year-old-healthy man, with previous history of parenteral drug abuse,
      developed a left homonymous hemianopsia. Computed tomographic scanning showed a
      single ring enhancing lesion in the right parieto-occipital area. After the
      demonstration of seropositivity for human immunodeficiency virus and high serum
      immunoglobulin G antibody titer against Toxoplasma gondii, a diagnosis of
      cerebral toxoplasmosis in an AIDS patient was made. An isolated visual field
      defect revealing cerebral toxoplasmosis may be the first presentation of AIDS.
      Opportunistic cerebral lesions should be always considered in subjects at risk
      for AIDS who present focal neurological signs.

PMID- 8259070
TI  - Electroretinogram and visual evoked potential in two siblings with adult form
      galactosialidosis.
AB  - We recorded flash electroretinograms (ERGs), flash visual evoked potentials
      (VEPs), pattern ERGs and pattern VEPs in two siblings with adult form
      galactosialidosis. The amplitude of b-wave was decreased in flash ERGs. The peak
      latency of flash VEPs was within normal range. The pattern ERGs and VEPs were
      nonrecordable. These results suggested the damage of retinal ganglion cell and
      inner nuclear layer in these cases.

PMID- 8259071
TI  - Ocular involvement correlated with age in patients affected by major and
      intermedia beta-thalassemia treated or not with desferrioxamine.
AB  - We examined 25 patients affected from Cooley's disease and five by beta
      thalassemia intermedia. The mean age was 15 +/- 6.3 years. Fifteen patients, (18
      years or older) three of them affected by beta-thalassemia intermedia, presented
      ocular abnormalities. So it was impossible to establish a correlation between
      laboratory data and ocular damages; their observation, with reference to
      untreated beta-thalassemia subjects, suggested that ocular abnormalities cannot
      be only attributed to desferrioxamine treatment.

PMID- 8259072
TI  - Most important option for health care program.

PMID- 8259073
TI  - Malignant fibrous histiocytoma of the ocular adnexa.
AB  - Malignant fibrous histiocytomas are common sarcomas of later life. They arise
      most commonly in the lower extremities and, only rarely, in the head and neck.
      Fibrous histiocytomas, mostly benign, have been reported in the orbit and
      conjunctiva, but only three benign lesions have been described in the eyelids. I
      present a case of malignant fibrous histiocytoma of the eyelid which recurred
      locally, but has shown no evidence of metastases.

PMID- 8259075
TI  - The ribosome as a source of genome hypervariability?
AB  - In this report it is suggested that at early stages of evolution ribosomes were
      responsible for synthesizing short oligonucleotide cDNA packets which formed the
      protogenic tandem repetitive sequences. Ribosomal RNA (rRNA) could have been the
      most probable template for such a synthesis. rRNA has homology with the monomers
      of tandem hypervariable repetitive elements of the genome. A model for the
      proposed participation of rRNA in the genesis of genomic fragments is provided by
      analysis of the active center of GTP-binding proteins. The role of
      oligonucleotides, synthesized by the ribosome, in the context of mechanisms of
      genome regulation, genes responsible for disease and human longterm memory
      formation are also discussed.

PMID- 8259074
TI  - Deformed optic chiasm and colloid cyst in a patient with visual disturbances.
AB  - Colloid cysts of the third ventricle are rare intracranial lesions which comprise
      0.5 to 1% of all intracranial tumors. We describe a patient with a third
      ventricle colloid cyst who presented with non specific visual deterioration.

PMID- 8259076
TI  - Beyond isolation: preferred rates of oscillation, from fireflies to epilepsy.
AB  - The observed light synchronism that comes naturally to a variety of oscillatory
      systems includes not only fireflies flashing in unison (1), but a number of other
      organisms and cells that have a preferred rate of oscillation. The observed
      motion of analogous phenomena such as these and brain cells that emit electric
      signals in rhythm (beneficial or detrimental) indicated by the frequency tracings
      of an electroencephalogram may contain many unexpected symmetries. In the
      investigation of these symmetries light could reveal itself to be the critical
      interface.

PMID- 8259077
TI  - The elastic constraint effect: a possible factor in renal perfusion.
AB  - An elastic constraint placed onto a distensible conduit modifies its perfusion
      characteristics. Surprisingly, a manifold increase in throughflow occurs as the
      resistance further downstream is increased. This flow anomaly occurs within a
      certain operating range of resistance settings.

PMID- 8259078
TI  - Light variability in the modern neonatal nursery: chronobiologic issues.
AB  - The role that nursery light variability may play in modulating infant biological
      rhythms is being studied in Stanford Medical Center's Neonatal Intensive Care
      (NICU) and Intermediate Care (IN) Nurseries. In this investigation, spatial and
      temporal variability in illuminance was determined at 20 sites within each
      nursery over a 5-day period. The analysis of 240 measurements at 30 min intervals
      from each site revealed marked variability in illumination with respect to both
      time and position in the nursery. These aperiodic lighting patterns differed
      greatly from the published characterization of NICUs as having 'constant'
      illumination. Light pulses of variable frequency, intensity, and duration were
      common at each of the 40 bedsites studied. Given the powerful impact of light on
      circadian rhythmicity and sleep in adults, the results from this study suggest
      that modern NICU lighting, while implemented to facilitate intensive care, may
      have adverse effects on infant development. Future studies on the influence of
      light on biological rhythmicity and sleep are essential to provide a framework
      for clinical and environmental interventions, which may play a significant role
      in improving developmental outcome in hospitalized preterm or term infants.

PMID- 8259079
TI  - Reduced inhibition of endothelial-derived relaxing factor causes the hyperdynamic
      circulation in chronic severe anemia.
AB  - Patients with chronic severe anemia have a vasodilated state and hyperdynamic
      circulation. The cause of vasodilation in these patients is not known. We
      postulate that the low levels of hemoglobin in these patients results in reduced
      inhibition of basal EDRF activity leading to generalized vasodilation.

PMID- 8259080
TI  - Late luteal phase dysphoric disorder: a scientific puzzle.
AB  - Late luteal phase dysphoric disorder is described as a classic biopsychosocial
      disorder resulting from complex interactions of biological, psychological,
      socioeconomic and cultural forces on women. To understand women suffering from
      the disorder, one must understand how the genetically designed female brain and
      body influence and are influenced by experience and learning. Each perspective of
      understanding constitutes one piece of a scientific puzzle. These perspectives
      are delineated and the conceptual problem of how to measure the outcome of the
      interactions is described.

PMID- 8259081
TI  - Is ANP responsible for the hemoconcentration in preeclampsia?
AB  - A hypothesis is presented that high plasma concentration of alpha-human Atrial
      Natriuretic Peptide (ANP) might be responsible for hemoconcentration of
      preeclampsia (PE), mediated by increased diuresis and shift of fluid to the
      interstitium. ANP is known as a peptide regulating blood volume by diuresis and
      natriuresis, and perhaps through increased permeability in vessels. Moreover ANP
      is an antagonist to the renin-angiotensin-aldosterone (RAA) system, especially
      when this system is activated quantitatively as in pregnancy or qualitatively as
      in PE.

PMID- 8259082
TI  - Hypothesis to explain the association between hypocalciuria and low circulating
      1,25-dihydroxyvitamin D levels in preeclampsia.

PMID- 8259083
TI  - A possible explanation of sudden infant death syndrome (SIDS).
AB  - Research into (lucid) dreaming has shown that the images of a dream are supported
      by the corresponding body actions, utilizing those muscles which remain active
      during dreaming. We suggest that Sudden Infant Death Syndrome (SIDS) or Cot Death
      may be a result of an infant dreaming about its life as a fetus. In the course of
      that dream, since a fetus does not breathe in the usual sense, the infant may
      cease to breathe and die. Our hypothesis is consistent with the known facts about
      SIDS, including social factors such as sleeping position and climatic variation.
      We suggest that the risk of SIDS can be reduced by making the environment of the
      infant, as much as possible, unlike that of the womb.

PMID- 8259084
TI  - HIV glycoprotein as a superantigen. A mechanism of autoimmunity and implications
      for a vaccination strategy.
AB  - The pathogenic effects of HIV may reflect mimicry of several key immunological
      molecules. The surface glycoprotein of HIV has superantigenic properties
      responsible for the sequential deletion of T-cell clones. In addition, the
      glycoprotein has several regions sharing homology with class II MHC products. It
      can elicit cross-reactive antibodies which block replenishment of these T-cells
      in the thymus. The usefulness of conventional vaccination strategies in the fight
      against AIDS has been subject to debate. Based on these considerations, we argue
      that effective vaccines should avoid viral sequences homologous to class II MHC
      proteins which might exacerbate this process.

PMID- 8259085
TI  - Transcriptional entrainment between master-slave genes via sister chromatid
      exchanges.
AB  - The paper discusses a mechanism for the coordination of a differentiation path
      through activation of slave genes by transcriptional complexes (excitons)
      organised by master genes. Entrainment occurs when master-slave genes form
      partnerships of closely apposed entities. Sister chromatid exchanges provide the
      action necessary for successful entrainment. Although concerned mainly with
      normal hematopoietic (stem) cells, the model applies also to certain leukemic
      cells, regarding in particular retrodifferentiation back to the stem state
      followed by attenuation of malignancy.

PMID- 8259086
TI  - On the translation of a soliton-like kink along the stack of a coiled chromatid.
AB  - The theory of solitons is applied to the normalisation of a malformed loop from a
      kinked chromatid. When interpreted in the context of dividing cells, the proposed
      mechanism adds novel functions to those traditionally attributed to the mitotic
      spindle.

PMID- 8259087
TI  - Apollonian dynamics, mitotic spindle and anaphase chromatids.
AB  - The so-called 'Apollonian gasket' offers interesting suggestions on how
      chromatids might be packaged among microtubular bundles of the mitotic spindle.
      While transiting through the spindle's viscous environment, the helical motions
      of coiled chromatids engender important interactions via synergistic or
      antagonistic torques that are instrumental for both shape and function of normal
      genomes as well as for certain anomalies (aneuploidy, nuclear deformations, etc)
      often associated to the malignant state.

PMID- 8259088
TI  - Instructed polarisation of sister chromatids.
AB  - We discuss a mechanism leading to antipodal polarisation of sister chromatids.
      The information to migrate to opposite poles originates from the interaction
      between spindle microtubules and the kinetochores when two sister chromatids
      disentangle from each other at the centromeric braid.

PMID- 8259089
TI  - Improving medical approaches to primary CNS malignancies--retinoid therapy and
      more.
AB  - Successfully inducing differentiation in ectodermal diseases, retinoids harbour
      considerable therapeutic potential in the treatment of neuroectodermal
      neuroepithelial malignancies. The principal tissue retinoid, retinoic acid, can
      be potently upregulated in vivo by a relatively specific catabolic inhibitor,
      R75251 (liarozole). Both substances have been given orally over 2 years in
      addition to standard treatment, and have been well tolerated. Corresponding
      closely to plasma retinoid levels, cutaneous side effects facilitate individual
      dosing. We evaluate this adjuvant retinoid approach and additional efforts to
      improve therapy of primary CNS malignancies, including the topical administration
      of retinoids in gamma linolenic acid.

PMID- 8259090
TI  - Contribution to problems of pseudohypoaldosteronism type I in children.
AB  - Pseudohypoaldosteronism Type I may occur due to several different causes. The
      authors recommend distinguishing between effector and receptor disorders with
      regard to the diverse mode of inheritance and prognosis.

PMID- 8259091
TI  - Psychosomatic dental disease: is mental stress in adults followed by acute dental
      caries in all racial groups?
AB  - The following data indicate that the onset of acute dental circles in adults,
      following severe mental stress, is seen not only in people of European stock but
      also in Polynesians and Micronesians. This suggests that this reaction to stress
      might occur in all races.

PMID- 8259092
TI  - Yersinia enterocolitica infection--an unrecognized cause of acute and chronic
      neurological disease? A 10-year follow-up study on 458 hospitalized patients.
AB  - The purpose of the present study was to obtain further information about nervous
      system involvement associated with Yersinia enterocolitica infection. During the
      period 1974-1983, the infection was diagnosed by antibody response (agglutination
      titer or ELISA) and/or isolation of the microorganism in 458 hospitalized
      patients. 2 patients presented with acute symptoms of the peripheral nervous
      system, and 6 with symptoms of the central nervous system. The 458 patients were
      followed for 4-14 years (until 1987). During the follow-up period another 6
      patients developed chronic neurological conditions; 4 with peripheral symptoms,
      and 2 with central symptoms. 11 of the 14 patients experienced persistent
      complaints. In 1991 (10-17 years after the diagnosis of yersiniosis), 6 patients
      still had significant antibody response (ELISA). The possibility that the
      immunologically competent Yersinia enterocolitica might have initiated the
      chronic neurological disease in these patients should not be disregarded.

PMID- 8259093
TI  - Extracellular purine nucleosides elevated in chronic recidiving central nervous
      injury by deranged metabolism in phenylketonuria.

PMID- 8259094
TI  - Therapy of disseminated malignant melanoma with recombinant alpha 2b-interferon
      and piroxicam: clinical results with a report of an unusual response-associated
      feature (vitiligo) and unusual toxicity (diffuse pulmonary interstitial
      fibrosis).
AB  - Fifteen patients with disseminated malignant melanoma were treated with
      recombinant alpha 2b-interferon (20 mU/m2 intravenously 5 days per week for 4
      weeks and then 10 mU/m2 subcutaneously tiw) and piroxicam (10 mg a day orally for
      10 days prior to beginning interferon and daily thereafter). Two complete
      responses of soft tissue disease and stabilization of disease in two other
      patients were obtained. One complete response was associated with the development
      of vitiligo. One patient who had entered complete remission was removed from the
      study because of diffuse pulmonary interstitial fibrosis, believed due to
      therapy. The combination of alpha 2b-interferon and piroxicam offers no clinical
      advantage over the use of alpha 2b-interferon alone.

PMID- 8259095
TI  - What is the prognostic value of osteomedullary uptake on MIBG scan in
      neuroblastoma patients under one year of age?
AB  - Twenty-seven infants under one year of age with metastatic neuroblastoma were
      studied for osteomedullary metastases. They were evaluated by at least two
      imaging procedures: X-ray films and MIBG scan. Taking into account the results of
      these investigations, 3 groups were defined: osteomedullary metastases were
      detected in 8 infants by both X-ray and MIBG scan, no osteomedullary sites were
      detected by either technique in 13 patients, and 6 had osteomedullary foci with
      positive MIBG uptake but no radiological abnormality. These three groups were
      apparently different in terms of median age, response to chemotherapy, and long
      term survival. The third group, which has not been previously described, appears
      to have a better prognosis than patients with radiologically detectable bone
      lesions. Nevertheless it was necessary to use intensive chemotherapy to obtain
      remission in these particular patients. It should be mandatory to specify the
      investigatory technique used to describe osteomedullary metastases in infants and
      treatment should be adapted according to this grouping system.

PMID- 8259096
TI  - CD10+ cell population in the bone marrow of patients with advanced neuroblastoma.
AB  - Immunocytologic analyses of bone marrow can provide clinically useful prognostic
      information in neuroblastoma. While analyzing the bone marrow with a panel of
      monoclonal antibodies, which detect neuroblasts and other defining B-, T-, and
      myloid lineage, we identified two infants with stage IV-S neuroblastoma whose
      bone marrow contained a large population of common acute lymphoblastic leukemia
      (ALL)-like cells. This population expressed HLA-DR, CD19(B1), CD10(CALLA), and
      occasionally CD20(B1). Since 1988, 17 additional patients with advanced
      neuroblastoma (IV-S, III, and IV) were studied by us. In 10 of the 19 patients,
      the bone marrow revealed an expanded CD10 population (20-70%). It appears that
      this group of patients has a better prognosis. Out of 9 patients who did not have
      an expanded CD10 population, 8 died within 9 months from diagnosis, whereas out
      of 10 patients with an expanded CD10 population only one died and the others are
      alive, 6-30 months from diagnosis (P < 0.001). An expanded CD10 population in the
      bone marrow of disseminated neuroblastoma patients may therefore serve as a
      prognostic factor. Apart from the prognostic value of this particular population
      in the single patient, its presence may shed light on the interrelationship
      between the immune system and the neuroendocrine compartment.

PMID- 8259098
TI  - Pilot study of sequential combination chemotherapy in advanced and recurrent
      retinoblastoma.
AB  - Eight patients with advanced/recurrent retinoblastomas were treated with
      sequential combination chemotherapy incorporating cyclophosphamide, cisplatin,
      adriamycin, and etoposide. All patients achieved complete clinical response (CR)
      at the end of the first 75 day cycle. Three patients developed recurrence of
      which 2 patients had recurrence in the central nervous system and 1 patient had
      local recurrence. Median time to treatment failure was 30 weeks. Two patients
      succumbed to chemotherapy related neutropenic sepsis. One patient is alive and
      disease free for 72 weeks from start of treatment. This combination chemotherapy
      shows promise in patients with advanced/recurrent retinoblastoma and merits
      further study.

PMID- 8259097
TI  - Treatment of relapsed or refractory acute leukemia in childhood with bisantrene
      combined with high dose aracytine.
AB  - Bisantrene is an anthracene derivative which has demonstrated activity in acute
      myeloblastic leukemia (AML) and in lymphoma. The present study was designed to
      assess the reinduction rate and toxicity of bisantrene (250 mg/m2/d x 5)
      associated with aracytine (100 mg/m2 twice a day x 5) in refractory and relapsed
      acute childhood leukemia. Patients who relapsed after bone marrow transplantation
      were eligible. Twenty-six children were included. Diagnoses were as follows: 13
      AML, 9 acute lymphoblastic leukemia (ALL), and 4 undifferentiated leukemia (AUL).
      All patients had been very highly pretreated, especially with anthracyclines, and
      most of them were of poor prognosis. The overall response rate was 46% with a 95%
      confidence interval ranging from 27-65%. According to diagnosis, complete
      remission (CR) rates are: AML: 5/13, ALL: 5/9, and AUL: 2/4. Four children died,
      three from infection and one from acute lysis syndrome. The major toxicity was
      infection with grade 3 and 4 episodes occurring in 42% of patients. No
      significant cardiac toxicity was noted. Hepatic and renal toxicity was noted.
      Hepatic and renal toxicity were limited and transient. Bisantrene in association
      with aracytine is effective in both AML and ALL of childhood. Bisantrene should
      be evaluated with a five-day schedule in other pediatric malignancies. In
      children with acute leukemia previously treated with high dose aracytine, new
      combination regimen is warranted.

PMID- 8259099
TI  - Paul Langerhans Jr. (1847-1888): a short life, yet two eponymic legacies.

PMID- 8259100
TI  - Wernicke-encephalopathy in children with cancer.

PMID- 8259101
TI  - Arteriovenous malformation mimicking recurrent medulloblastoma.
AB  - Magnetic resonance imaging (MRI) is becoming the method of choice for evaluation
      of central nervous system tumors. However, the sensitivity of this modality
      raises concern that new lesions in patients previously diagnosed with a brain
      tumor may not necessarily represent recurrent disease. We report a patient
      previously treated with surgery, radiotherapy, and chemotherapy for a
      medulloblastoma who developed a new lesion in the floor of the fourth ventricle.
      Histologic review following excision revealed an arteriovenous malformation.

PMID- 8259102
TI  - Anaplastic large cell lymphoma of true histiocytic origin in an infant: unusual
      clinical, hematological, and cytogenetic features.
AB  - We report here the case of a 7-month-old boy who developed anaplastic large cell
      lymphoma of true histiocytic origin or malignant histiocytosis, with fever, bone
      and bone marrow infiltration. Usual clinical features were absent. The neoplastic
      nature of the disease was supported by the presence of clonal chromosomal
      abnormalities [t(6;8)(p23;p21),der(8)del(8)(q11aq13), der(22) t(11;22) (q13;13)].
      Neither B nor T lineage could be demonstrated here. Morphology, ultrastructural
      analysis, surface antigens expression, and cytogenetics were more specific for
      the monocyte-macrophage lineage.

PMID- 8259103
TI  - Ifosfamide nephrotoxicity in children.

PMID- 8259104
TI  - Nutritional status of children with leukemia.
AB  - Children with cancer represent a high-risk group for protein-energy malnutrition
      due to side effects associated with treatment. Assessment of nutritional status
      at the time of diagnosis and during treatment is, therefore, essential for
      planning nutritional intervention. We studied the nutritional status of 25
      children with leukemia [9 newly diagnosed/relapsed (D/R) leukemic patients and 16
      children with leukemia in remission (REM)]. Plasma proteins (prealbumin, PA;
      albumin, Alb; transferrin, Tr; retinol-binding protein, RBP) and acute phase
      reactant proteins (alpha 1-acid glycoprotein, AGP; C-reactive protein, CRP;
      ceruloplasmin, CER) were measured by radial immunodiffusion. Results show that
      there were no significant deficits in anthropometric measurements among leukemic
      children. In contrast, the mean levels of all plasma proteins, especially PA (P <
      0.005), were significantly lower in the D/R group than in the REM group. All D/R
      children, compared to 59% of those in remission, had PA levels < 20 mg/dl. Only
      the D/R group had abnormal levels of RBP, Tr, and Alb. Children who were treated
      with prednisone had significantly higher mean levels of PA, RBP, and AGP than
      those who were not receiving prednisone. The mean levels of acute phase-reactant
      proteins in these leukemic children were comparable to those of healthy children.
      We conclude that mild/moderate malnutrition is common in leukemic patients at D/R
      and that PA seems to be the most sensitive indicator of visceral protein status.

PMID- 8259105
TI  - Neurofibromatosis type I and malignancy: review of 32 pediatric cases treated at
      a single institution.
AB  - Thirty-two cases of neurofibromatosis Type I (NF1) were identified among 6,678
      pediatric cancer patients treated at St. Jude Children's Research Hospital over a
      29-year period. A total of 35 malignant neoplasms have been diagnosed in these
      patients. Two of three patients with second malignant neoplasms had colon cancer
      at the primary or second tumor. Of particular interest are two cases in which
      both NF1 and malignant peripheral nerve sheath tumors were present in multiple
      successive generations: a patient with colon cancer and non-Hodgkin lymphoma who
      has a constitutional abnormality of the p53 gene, and a patient with acute
      lymphoblastic leukemia with the Philadelphia chromosome and other cytogenetic
      abnormalities, including the t(8;14). Outcome of patients in the largest
      subgroup, that of malignant peripheral nerve sheath tumors, was favorable only
      for those patients having resectable extremity lesions. In contrast, all patients
      with central nervous system tumors are surviving. These cases reflect the
      molecular and cytogenetic abnormalities that can be present in NF1 and the
      variety of tumors that may result in these patients.

PMID- 8259106
TI  - Methotrexate content in squamous cell carcinoma of the head and neck after low
      dose methotrexate.
AB  - Eleven patients with squamous carcinoma of the head and neck who were scheduled
      for surgical resection or endoscopic biopsy of tumor received 15 mg/m2 of
      methotrexate (MTX). Samples of tumor, normal mucosa, and plasma were obtained at
      surgery or endoscopy, 18-24 hours after the last MTX dose. Tissue content and
      plasma concentration of MTX and folate were measured using sequential radioligand
      binding assays. Median MTX content was 50.0 pmol/g wet weight in tumor, 19.0 in
      normal mucosa, and < 0.5 nM (pmol/ml) in plasma. Since dihydrofolate reductase
      (DHFR) content of human tumors has previously been shown to be less than 5 pmol
      enzyme/g wet weight, tumor MTX content exceeded expected DHFR content in all but
      one patient. These data support the concept that low doses of MTX saturate tumor
      DHFR and that, in this regard, dose escalation may have limited value.

PMID- 8259107
TI  - Factors that influence the further survival of patients who survive for five
      years after the diagnosis of cancer in childhood or adolescence.
AB  - To evaluate the further survival, and to identify disease and treatment factors
      which influence the further survival, of five-year survivors of cancer diagnosed
      during childhood or adolescence, we reviewed the courses of 591 previously
      untreated patients who were less than 20 years of age at diagnosis and survived
      for five years after diagnosis. Fifty-three of 143 patients who experienced
      disease recurrence during the first five years after diagnosis died during the
      period of observation, compared to 18 of 448 patients who did not experience
      disease recurrence during the first five years after diagnosis. The sex-specific
      standardized mortality ratios for the group of patients who never relapsed or
      relapsed more than five years after diagnosis were not significantly different
      from those of the New York State population. Cox proportional hazards modelling
      of the subgroup of patients who relapsed during the first five years after
      diagnosis demonstrated that disease which was treated surgically, a diagnosis of
      Hodgkin's disease or acute lymphoblastic leukemia, and older age at diagnosis
      were significantly associated with further survival in this group, whereas
      similar modelling of the patients who did not experience disease recurrence
      during the first five years after diagnosis failed to identify any variables
      which were associated with continued survival. The results of this study suggest
      that childhood and adolescent cancer patients who survive for five years without
      disease recurrence have a survival rate similar to that of the general
      population. Continued follow-up of this cohort is required to determine if the
      present findings can still be demonstrated as the majority of the cohort ages
      beyond 35 years of age.

PMID- 8259108
TI  - Improper infection-control practices during employee vaccination programs-
      District of Columbia and Pennsylvania, 1993.
AB  - The improper use of needles and syringes and contamination of multidose
      medication vials can result in transmission of bloodborne pathogens (e.g.,
      hepatitis B virus [HBV] and human immunodeficiency virus [HIV]) and other
      infectious agents from patient to patient. Since September 1993, CDC has received
      reports from health-care providers and public health departments in two U.S.
      cities regarding improper infection-control practices during vaccination of
      employees at worksite vaccination programs. These practices could potentially
      have exposed vaccine recipients to infectious agents. This report summarizes the
      preliminary findings of an ongoing investigation of these reports.

PMID- 8259109
TI  - Update: respiratory syncytial virus activity--United States, 1993.
AB  - Respiratory syncytial virus (RSV), a common cause of community-wide outbreaks of
      acute respiratory disease, is associated with an estimated 90,000
      hospitalizations and 4500 deaths from lower respiratory tract disease in both
      infants and young children in the United States. Outbreaks usually occur from
      late fall or early winter through spring. Since 1989, RSV activity in the United
      States has been monitored by the National Respiratory and Enteric Virus
      Surveillance System (NREVSS), a voluntary, laboratory-based system. This report
      summarizes surveillance results from NREVSS for RSV detections from July 1, 1993,
      through December 11, 1993, and assesses trends in RSV from July 1, 1990, through
      December 11, 1993.

PMID- 8259110
TI  - Status of public health--Bosnia and Herzegovina, August-September 1993.
AB  - Since 1991, civil strife in the former Yugoslav republics (Figure 1) has resulted
      in more than 150,000 war-related casualties, approximately 3.5 million displaced
      persons, widespread destruction of the health infrastructure, disruption of food
      production and distribution, and other increased risks to public health. The
      impact of the war has been especially severe in Bosnia and Herzegovina (1991
      population: 4.3 million). To assist in targeting humanitarian aid to the region,
      in August 1993, the U.S. Agency for International Development's Office of Foreign
      Disaster Assistance asked CDC to assess the public health status and needs of
      Bosnia and Herzegovina. This report summarizes the results of that assessment and
      focuses on three central Bosnian regions.

PMID- 8259111
TI  - A brief thesaurus of quality.

PMID- 8259112
TI  - Quality, Deming's principles, and physicians.

PMID- 8259113
TI  - Risk management in health care: where did it come from and where is it going?
AB  - This article reviews some of the historical developments contributing to the
      evolution of risk management and its current role in health care. The scope of
      activities and concerns that today's health care risk managers address and the
      need for involvement by the entire health care team are discussed.

PMID- 8259114
TI  - A century of progress: nursing quality improvement at the Mount Sinai Medical
      Center.
AB  - Since The Mount Sinai Hospital in New York City began delivering care in the mid
      1800s, the medical services and, shortly thereafter, the nursing service have
      consistently given priority to improving patient care. Through the decades of the
      late 19th and 20th centuries, the Department of Nursing has remained current with
      the evolving concept of quality improvement. A historical overview of key
      elements in the evolution of quality improvement in nursing is presented.

PMID- 8259115
TI  - Social work accountability: a key to high-quality patient care and services.

PMID- 8259116
TI  - Patient representation as a quality improvement tool.
AB  - In the late 1960s, healthcare institutions began to appoint patient
      representatives, also called patient advocates or ombudsmen, to counter
      complaints about unsatisfactory and impersonal delivery of care. Patient
      representatives are now employed in over half the hospitals in the United States
      as well as in nursing homes, clinics, health maintenance organizations, and other
      health provider organizations. At The Mount Sinai Hospital in New York City, the
      Patient Representative Department was established in 1966 to provide greater
      access to the institution for community residents, to help solve patients'
      problems and complaints, and to serve as a quality assessment and improvement
      tool. It functions as both a proactive and reactive force, addressing patients'
      concerns, investigating sources of dissatisfaction, recommending corrective
      action when policies and procedures are not responsive to patient needs, and
      striving to create a patient-friendly environment.

PMID- 8259117
TI  - Prevention of medication errors. Developing a continuous-quality-improvement
      approach.
AB  - Medication errors can be a serious problem that exposes patients to preventable
      risks. Although medication errors are often considered primarily a nursing issue,
      every health care provider plays an important role in medication error
      prevention. A continuous quality improvement philosophy with involvement of a
      multidisciplinary team is the optimal method for identifying and correcting the
      causes of medication errors. Careful analysis of the medication distribution
      system and identification of system flaws is an integral part of the continuous
      quality improvement process.

PMID- 8259118
TI  - Quality improvement in action: a falls prevention and management program.
AB  - A departmental program for falls prevention and management, initiated in 1987,
      and arising out of the awareness of the economic, physical, and psychological
      effects of falls in hospitalized patients, has been described. Given the results
      outlined, there is no doubt that the efforts applied in the area of falls
      prevention have been extremely worthwhile in affecting major quality improvements
      in patient care. The benefits of the falls prevention program include a reduction
      in the incidence of falls as well as an increased awareness by staff, patients,
      and families of the importance of monitoring patients at risk for falls.

PMID- 8259119
TI  - Research in the hospital setting on human subjects. Protecting the patient and
      the institution.
AB  - A hospital's institutional review board is charged with the responsibility of
      fully protecting the rights of research subjects. In doing so, the board
      establishes that research protocols are based on sound scientific principles,
      that benefits to research subjects outweigh the risks, and that the subject's
      consent is informed and not coerced. Although it has been argued that risk
      management has no role in the activities of such boards, the literature indicates
      that risk management and quality assurance principles apply to all areas of the
      institution, including the activities of the board. The institution must ensure
      that its researchers and board members are as fully protected as possible from
      civil and criminal liability and that the integrity of those conducting the
      research is established and maintained. The institution must also provide
      sufficient support for the board to conduct its reviews and educate the research
      community and board members on current and evolving laws and regulations
      governing human research. Risk prevention and quality assurance strategies should
      recognize the rights of the research subject as paramount while protecting the
      institution, its researchers, and the community served.

PMID- 8259120
TI  - The consumer survey review process: a pathway to quality.
AB  - This paper describes the consumer survey review process (CSRP), a vehicle for
      continuous improvement of patient care quality at The Mount Sinai Hospital in New
      York City. Following a historical sketch of the events which led to its
      establishment at Mount Sinai, we then describe the instrument used to elicit
      patients' rating of service delivery, the Consumer Survey, and show how it meets
      the changing requirements of those who use it. Next, we explain the role and
      functioning of the management group that most directly translates the patient
      satisfaction data into action, the Consumer Survey Review Group. Finally, we
      discuss implications of Mount Sinai's consumer survey review process for managing
      quality in health care.

PMID- 8259121
TI  - Controversies on screening for cancer of the prostate.

PMID- 8259122
TI  - The developmentally regulated trans-sialidase from Trypanosoma brucei sialylates
      the procyclic acidic repetitive protein.
AB  - A developmentally regulated trans-sialidase activity is present on the surface of
      procyclic Trypanosoma brucei. Bloodstream stages display no trans-sialidase
      activity. T. brucei trans-sialidase is capable of transferring sialic acids from
      a variety of glycoconjugates into new glycosidic linkages without requirement for
      CMP-Neu5Ac. The enzyme is linked to the plasma-membrane via a GPI-PLC-resistant
      GPI-anchor. The comparison of enzymic and structural features of sialidase and
      trans-sialidase suggests that the two activities may be catalyzed by the same
      protein, since highly enriched sialidase fractions display trans-sialidase
      activity. 2-Deoxy-2,3-didehydro-N-acetylneuraminic acid is only a poor inhibitor
      for the two enzymic activities. Sialic acids are transferred to alpha (2-3)
      positions of terminal beta-galactose residues of oligosaccharides and
      glycoconjugates at various rates. Neu5Ac-alpha(2-3)-lactose is the best trans
      sialylation donor tested. Lewis is a poor sialic acid acceptor. T. brucei trans
      sialidase utilizes serum glycoconjugates, human and bovine erythrocytes as sialic
      acid donors, and resialylates sialidase-treated erythrocytes. The enzyme
      transfers sialic acids from the GPI-anchor of procyclic acidic repetitive protein
      (PARP) onto lactose and vice versa. Also structures within a variant surface
      glycoprotein (sVSG MITat. 1.7.) can be trans-sialylated.

PMID- 8259123
TI  - Abrupt RNA changes precede the first cell division during the differentiation of
      Trypanosoma brucei bloodstream forms into procyclic forms in vitro.
AB  - We have monitored the timing of DNA and RNA synthesis during the synchronous
      differentiation of Trypanosoma brucei bloodstream forms into procyclic forms in
      vitro. Both are triggered after a lag period of 4 h and reach a first peak after
      9 h. The division of the kinetoplast precedes that of the nucleus by about 4 h.
      The first cell divisions are observed after 10 h, and the cell number is doubled
      after 20 h. The total RNA content per cell increases sharply between 4 and 10 h,
      then progressively decreases as cell division progresses. The increase in RNA
      content cannot be due solely to accumulation of rRNA since it is also observed
      for mRNAs such as actin. The VSG mRNA has almost disappeared within 2 h, while
      the procyclin mRNA accumulates soon after the triggering of differentiation, with
      a strong peak between 4 and 6 h. At this moment, the amount of procyclin mRNA per
      cell is at least 20-fold higher than in established procyclic culture forms. The
      loss of the VSG and the appearance of procyclic-specific proteins essentially
      occur before the first cell division. These observations contrast with the
      progressive transition observed when monomorphic slender forms are induced to
      transform under the same conditions.

PMID- 8259124
TI  - Transient adenylate cyclase activation accompanies differentiation of Trypanosoma
      brucei from bloodstream to procyclic forms.
AB  - Pleomorphic bloodstream forms of Trypanosoma brucei differentiate synchronously
      into procyclic forms when cultivated at 27 degrees C in the presence of
      citrate/cis-aconitate. The activity of adenylate cyclase was monitored during
      this process. Two phases of transient stimulation were observed. The first phase
      occurred 6-10 h after the triggering of differentiation, a period which
      immediately follows the release of the bulk of the VSG and immediately precedes
      both the first cell division and the loss of the bloodstream-specific ESAG 4
      transmembrane adenylate cyclase. The second phase occurred between 20 and 40 h,
      when the cells that emerged from the first division began to proliferate. These
      observations suggest that cAMP may be involved in differentiation/proliferation
      of the parasite.

PMID- 8259125
TI  - Organization of mini-exon and 5S rRNA genes in the kinetoplastid Trypanoplasma
      borreli.
AB  - Mini-exon gene repeats from Trypanoplasma borreli, which belongs to the
      Cryptobiidae family of the Bodonina suborder of the Kinetoplastida, were isolated
      by PCR amplification and cloning. The presence of kinetoplastid-like mini-exon
      genes in T. borreli is consistent with the taxonomic status of this organism as a
      kinetoplastid protozoan. Two families of repeats were found: 597 nt (T1) and 794
      nt (T2), each of which encodes an approximately 95-nt medRNA transcript. The T1
      repeats also contain a complete 5S rRNA gene on the complementary strand. The T2
      repeats contain a defective copy of a 5S gene, in which the 5' portion is absent.
      The intergenic regions between the 5'-ends of the mini-exon genes and the 5S rRNA
      genes in the T1 and T2 repeats are highly diverged. All or most mini-exon genes
      and 5S genes are located within either the T1 or the T2 repeats. The T1 repeats
      were localized to a megabase-size chromosome, while the T2 repeats were localized
      within at least 4 large chromosomes.

PMID- 8259126
TI  - Expression of Toxoplasma gondii P30 as fusions with glutathione S-transferase in
      animal cells by Sindbis recombinant virus.

PMID- 8259127
TI  - The expression of a small heat shock protein homologue is developmentally
      regulated in Nippostrongylus brasiliensis.

PMID- 8259129
TI  - Cysteine is the major low-molecular weight thiol in Giardia duodenalis.

PMID- 8259128
TI  - Digital codes from hypervariable tandemly repeated DNA sequences in the
      Plasmodium falciparum circumsporozoite gene can genetically barcode isolates.
AB  - DNA typing systems currently used in parasitology involve either hybridising
      Southern blots with repetitive sequence probes or amplifying genomic sequences
      using the polymerase chain reaction (PCR). Both such approaches assay allelic
      length variation, usually in unexpressed tandemly repeated DNA sequences. Where
      an appropriate target locus exists, an alternative PCR-based strategy which
      reveals allelic sequence variation in tandemly repeated DNA offers a more
      accurate and internally controlled assay. We describe such a strategy for the
      rapid extraction of information on tandem repeat sequence variation from
      hypervariable alleles, and apply it to the Plasmodium falciparum CS gene. The
      extreme variability of such DNA 'barcodes' can be used to identify parasite
      stocks and lineages. This system is also potentially useful for population
      genetic and epidemiological studies since it offers the possibility of following
      the spread of distinctively marked parasite genotypes in samples taken from
      infected individuals.

PMID- 8259130
TI  - Characterization of novel fucosyl- and tyvelosyl-containing glycoconjugates from
      Trichinella spiralis muscle stage larvae.
AB  - The monosaccharide composition of an affinity-purified family of antigenically
      related Trichinella spiralis larval glycoproteins was determined by gas
      chromatography/mass spectrometry. This group of 6 major glycoproteins, designated
      TSL-1, originates in the muscle stage (L1) larval stichosome. They are present on
      the L1 surface and in excretory/secretory products of L1 larvae, are stage
      specific, and are highly immunodominant. The glycosyl composition of the TSL-1
      antigens was remarkable in 2 respects: (1) fucose accounted for 36 molar percent
      of the glycosyl residues; and (2) a 3,6-dideoxyhexose was identified, which
      accounted for at least 24 molar percent of the glycosyl residues. Previously, 3,6
      dideoxyhexoses have been found only in certain Gram-negative bacterial
      lipopolysaccharides and in ascaroside alcohols (ascarylose) of Ascaris eggs. The
      3,6-dideoxyhexose found in the TSL-1 antigens also was found in ES. This
      Trichinella sugar has been chemically identified as a 3,6-dideoxyarabinohexose,
      the same as found in Ascaris eggs. However, the absolute configuration of the TSL
      1 sugar is D-(tyvelose), not L-(ascarylose) as is found in Ascaris eggs.
      Methylation analysis indicated that the TSL-1 3,6-dideoxy-D-arabinohexose was
      present entirely as non-reducing terminal residues. Approximately 83% of the
      fucose was also present as non-reducing terminal residues, with the remaining
      fucose found as 3,4-linked branched residues.

PMID- 8259131
TI  - Molecular characterization of the largest subunit of Plasmodium falciparum RNA
      polymerase I.
AB  - Plasmodium species possess developmentally regulated ribosomal RNA (rRNA) genes.
      This report describes the expression and gene structure of the largest subunit of
      P. falciparum RNA polymerase I (RNAPI), which is responsible for the synthesis of
      rRNA. The RNAPI largest subunit gene was present as a single copy gene on
      chromosome 9. Three exons encode the 2910-amino acid RNAPI polypeptide (340 140
      Da). A comparison of Plasmodium, Trypanosoma, and Saccharomyces cerevisiae
      nuclear RNAP largest subunits identified conserved amino acid positions and class
      specific amino acid positions. Novel amino acid insertions were found between
      RNAPI conserved regions A and B (region A'), D and DE1 (region D'), DE2 and E
      (region DE2'), and F and G (region F'). Leucine zipper domains were found within
      regions D', DE2, and DE2'. A novel serine-rich repeat domain, a domain with
      homology to the C-terminal domain of eukaryotic upstream binding factor (UBF),
      and 4 highly conserved casein kinase II (CKII) Ser/Thr phosphorylation motifs
      were found within a 127-amino acid sub-region of enlarged region F'. The novel
      RNAPI serine-rich repeat contained a conserved motif, Ser-X3-Ser, which was also
      identified in the serine-rich repeat domains of the P. falciparum RNAPII and
      RNAPIII largest subunits, as well as within a highly homologous serine-rich
      repeat from trophozoite antigen R45. The results of this molecular analysis
      indicate that phosphorylation and dephosphorylation mechanisms regulate the
      activity of P. falciparum RNAPI.

PMID- 8259132
TI  - The transport and metabolism of alanine by Giardia intestinalis.
AB  - The transport and metabolism of L-alanine by Giardia intestinalis trophozoites
      was characterised. G. intestinalis formed 14CO2 from L-[1-14C]alanine (1 mM) at a
      rate of 4.8 nmol min-1 (mg protein)-1 at 30 degrees C. The system was saturable,
      with an apparent Km of 0.29 mM for alanine, and a maximal rate of 6.1 nmol min-1
      (mg protein)-1. L-cycloserine inhibited the metabolism, as did a number of amino
      acids including glycine, serine and threonine. D-alanine and 2-aminoisobutyrate
      had no effect. G. intestinalis was shown to have a functional transport system
      for L-alanine. The transporter was saturable with a Km of 1.5 mM and a maximal
      velocity of 6.1 nmol min-1 (mg protein)-1 at 23 degrees C. It was temperature
      dependent, with a Q10 of 2.2 and activation energy of 15.9 kcal mol-1. It was not
      inhibited by potential inhibitors of energy dependent transport. Glycine, L
      serine and L-threonine potently inhibited L-alanine transport, whereas D-alanine,
      beta-alanine and 2-aminoisobutyrate had no effect. L-serine competitively
      inhibited L-alanine influx. In trophozoites preloaded with [3H]alanine, rapid
      exchange occurred with external L-alanine and L-serine, but not with D-alanine
      confirming that L-alanine and L-serine share a common transport site. These
      observations indicate that G. intestinalis has a functional alanine transporter,
      which may be an antiport catalysing the exchange of alanine, serine, glycine and
      threonine.

PMID- 8259133
TI  - Cloning and expression of the gene coding for the transmission blocking target
      antigen Pfs48/45 of Plasmodium falciparum.
AB  - The gene encoding the gametocyte/gamete-specific membrane protein Pfs48/45 of
      Plasmodium falciparum has been cloned. The Pfs48/45 gene is a non-interrupted,
      single copy gene that codes for a hydrophobic, non-repetitive protein of 448
      amino acid residues containing a putative signal peptide at the N-terminus, a
      hydrophobic C-terminus and 7 potential N-glycosylation sites. Antibodies directed
      against a Pfs48/45-glutathione-S-transferase fusion protein reacted with both the
      45-kDa and 48-kDa proteins of gametocytes. When Pfs48/45 is expressed in the
      baculovirus-insect cell system the recombinant Pfs48/45 protein is targeted and
      exposed to the insect cell surface in such a configuration that it is recognized
      by transmission-blocking anti-45/48-kDa monoclonal antibodies.

PMID- 8259134
TI  - Genotyping isolates and clones of Giardia duodenalis by polymerase chain
      reaction: implications for the detection of genetic variation among protozoan
      parasite species.
AB  - Detection of genetic variation among microorganisms can be done by DNA
      fingerprinting using the polymerase chain reaction (PCR). Application of primers
      directed to polymorphic DNA leads to the amplification of DNA fragments which
      differ in length when different species or isolates of a single species are
      compared. It has been demonstrated that PCR primers resembling eukaryotic repeat
      motifs enable the straightforward genetic differentiation of Giardia duodenalis
      isolates. Depending on the repeat motif, genetic variation between cloned G.
      duodenalis lines could also be detected. DNA polymorphisms could also be detected
      by random amplification of polymorphic DNA (RAPD) analyses. When the results
      obtained for G. duodenalis are compared to those found for another protozoan
      parasite, Naegleria fowleri, clear differences are encountered. In contrast to
      the findings for G. duodenalis, the repeat motif primers did not allow the
      discrimination of 'N. fowleri isolates. Apparently, as determined by this PCR
      mediated genotyping, genetic variation occurs in G. duodenalis with increased
      frequency at the isolate level as compared to N. fowleri. The possible
      implications of this observation for clonality or the definition of a species in
      protozoan parasites will be discussed.

PMID- 8259135
TI  - Trypanothione-dependent peroxide metabolism in Trypanosoma cruzi different
      stages.
AB  - Different stages of Trypanosoma cruzi are able to metabolize low concentrations
      of H2O2. Trypomastigotes showed a higher initial rate per mg protein than
      amastigotes or epimastigotes derived from them. Amastigotes could metabolize H2O2
      at a lower rate than the other developmental stages of T. cruzi. A peroxide
      metabolizing activity was detected in extracts of T. cruzi epimastigotes. This
      'NADPH peroxidase' activity was lost upon dialysis of the extracts and was
      probably due to a non-enzymatic reaction(s) with endogenous dihydrotrypanothione
      (T(SH)2) and/or other thiols, thus explaining the inhibition of H2O2 metabolism
      in intact cells by thiol inhibitors. An amount of non-protein thiols equivalent
      to an intracellular concentration of 2.0-3.0 mM was found in epimastigotes, which
      is sufficient to account for the rate of NADPH oxidation observed in the presence
      of high concentration of peroxides (> 100 microM). Addition of T(SH)2 increased
      this rate, implying that this thiol could be used as a substrate in that
      reaction. In addition, this activity was hardly detectable in the extracts in the
      presence of low concentration of peroxides (< 20 microM), indicating a high Km,
      which would be incompatible with a true peroxidase activity. Taking into account
      the high intracellular concentration of thiols measured, this activity probably
      accounted for the rates of H2O2 metabolism detected in intact T. cruzi. These
      results also confirm that T. cruzi is an organism with limited ability to
      detoxify H2O2.

PMID- 8259136
TI  - A possible role for the 3'-untranslated region in developmental regulation in
      Trypanosoma brucei.
AB  - A series of Trypanosoma brucei transfection vectors was constructed in which
      transcription of the luciferase gene was driven by the procyclic acidic
      repetitive protein (procyclin) promoter. The untranslated regions surrounding the
      luciferase gene were derived from the actin, fructose bisphosphate aldolase, or
      PARP loci. Trans-splicing of the resulting transcripts occurred as expected, but
      the site of 3' polyadenylation was upstream of the position anticipated. The
      nature of the 3'-untranslated region was crucial to the level of expression in
      bloodstream forms.

PMID- 8259137
TI  - Trans-sialidase from Trypanosoma cruzi epimastigotes is expressed at the
      stationary phase and is different from the enzyme expressed in trypomastigotes.
AB  - We have studied the trans-sialidase from insect forms of Trypanosoma cruzi
      growing in axenic culture. Log phase epimastigotes expressed little or no trans
      sialidase activity, and were unable to incorporate exogenous sialic acid.
      Transsalidase started to be expressed at the late logarithmic phase, with
      specific activity increasing steadily as the culture reached the stationary
      phase. Trans-sialidase was purified from the late log phase epimastigote culture,
      which contained less than 2% of metacyclic forms, yielding a glycoprotein that
      migrated as a single 90-kDa band in sodium dodecyl sulfate gels. This enzyme
      features: (1) no reaction with antibodies against the peptide repeats present in
      the carboxy-terminal of trypomastigote trans-sialidase; (2) positive reaction
      with antibodies raised against a fragment of trypomastigote trans-sialidase that
      contains the active site; (3) similar kinetic properties and identical acceptor
      donor specificity when compared to the trypomastigote enzyme; and (4)
      neuraminidase activity in the absence of acceptors. Upon differentiation into
      metacyclic forms, a trans-sialidase activity containing the carboxy-terminal
      repeats of the trypomastigote enzyme was released into the medium. These results
      suggest that epimastigotes express a developmentally regulated trans-sialidase
      that contains the same catalytic site but lacks the tandem amino acid repeats
      typical of trypomastigote trans-sialidase.

PMID- 8259138
TI  - Replacement of the aortic root with a pulmonary autograft in children and young
      adults with aortic-valve disease.
AB  - BACKGROUND: The optimal substitute for severely diseased aortic valves in
      children and young adults is unknown. The use of a mechanical prosthesis requires
      permanent treatment of the patient with anticoagulants and is associated with
      thromboembolic and hemorrhagic complications. Aortic-valve allografts and porcine
      bioprostheses, which do not necessitate anticoagulant therapy, may deteriorate
      and have limited durability. METHODS: We therefore evaluated the use of the
      autologous pulmonary valve (i.e., the patient's own pulmonary valve) and the
      adjacent pulmonary artery as a replacement for the aortic valve and aortic
      sinuses in 33 patients. Five of the patients were from 8 to 16 years of age, and
      28 were from 20 to 47 years of age. The pulmonary valve and the main pulmonary
      artery were used to replace the diseased aortic valve and the adjacent aorta. The
      coronary arteries were detached from the aorta and implanted into the pulmonary
      artery. The pulmonary valve and artery were replaced with a cryopreserved
      pulmonary allograft. RESULTS: There were no deaths during follow-up of up to 48
      months (mean, 21 months). There were no episodes of infective endocarditis, and
      no reoperations on the aortic root were necessary. Also, there was no evidence on
      echocardiography of progressive dilatation of the autografts. With color-flow
      Doppler imaging, 22 patients were found to have only trivial regurgitation or
      none, 9 patients to have mild regurgitation, and no patients to have moderate or
      severe regurgitation across the autograft at the most recent follow-up visit. The
      mean peak velocity of flow across the autograft was 1.3 m per second (upper limit
      of normal, 1.8), indicating the absence of stenosis. One patient required
      reoperation for stenosis of the pulmonary allograft. CONCLUSIONS: Although the
      pulmonary-autograft procedure is more complex than simple aortic-valve
      replacement, it has been safely applied in selected patients, including young
      adults. Intermediate follow-up indicates satisfactory function of the autografts,
      with no dilatation or progressive valvular regurgitation. Pulmonary-root
      autografts may thus be the best available substitute for diseased aortic valves
      in children and young adults.

PMID- 8259139
TI  - Declining incidence of nephropathy in insulin-dependent diabetes mellitus.
AB  - BACKGROUND: The high relative mortality among patients with insulin-dependent
      diabetes mellitus results mainly from diabetic nephropathy. The cumulative
      incidence of nephropathy of 25 to 30 percent among patients who had had diabetes
      for 25 years remained stable from 1950 to the early 1980s. In a population study,
      we assessed recent trends in the incidence of diabetic nephropathy. METHODS: We
      studied all 213 patients in whom insulin-dependent diabetes mellitus was
      diagnosed before the age of 15 years between 1961 and 1980 in a district in
      southeastern Sweden. Ninety-two percent of the patients were followed from the
      onset of diabetes to 1991 or to death. Patients with persistent albuminuria
      (positive Albustix test) were considered to have diabetic nephropathy.
      Glycosylated hemoglobin was measured periodically in all patients, beginning in
      1980. RESULTS: The cumulative incidence of persistent albuminuria after 25 years
      of diabetes decreased from 30.0 percent among the patients in whom diabetes
      developed in the period 1961 to 1965 to 8.9 percent among those in whom it
      developed from 1966 to 1970 (P = 0.01). After 20 years of diabetes, the
      cumulative incidence decreased from 28.0 percent among the patients in whom
      diabetes developed from 1961 to 1965 to 5.8 percent among those in whom it
      developed from 1971 to 1975 (P = 0.01). Persistent albuminuria has not yet
      developed in any patient in whom diabetes was diagnosed in the period 1976 to
      1980. The average glycosylated hemoglobin value decreased from 7.4 percent in the
      period 1980 to 1985 to 7.0 percent from 1986 to 1991 (P < 0.001). The mean
      glycosylated hemoglobin value was higher in the patients with persistent
      albuminuria than the patients with no albuminuria (8.1 percent vs. 7.1 percent, P
      < 0.001). CONCLUSIONS: During the past decade the cumulative incidence of
      diabetic nephropathy, as manifested by persistent albuminuria, among patients who
      have had diabetes for 25 years has decreased substantially, probably as a result
      of improved glycemic control.

PMID- 8259140
TI  - Elevation of serum creatine kinase in divers with arterial gas embolization.
AB  - BACKGROUND: Arterial gas embolism due to pulmonary barotrauma and the resultant
      cerebral gas embolism are catastrophic complications of diving. Previous studies
      have only rarely noted evidence of gas embolism to noncranial sites. METHODS:
      Among 142 persons with diving-related injuries evaluated between January 1982 and
      July 1991, we identified 29 who had arterial gas embolism and who underwent
      biochemical studies indicative of muscle injury. Of the 29 patients, 4 were
      excluded because cardiopulmonary resuscitation had been performed and 3 were
      excluded because the duration of their dives met or exceeded standard limits set
      for dives not requiring staged decompression. The outcome at the time of hospital
      discharge in the remaining 22 patients was correlated with clinical factors and
      the results of biochemical studies. We also studied 22 subjects after
      uncomplicated dives and 11 patients who had sustained blunt trauma. RESULTS: All
      the patients with diving-associated gas embolism had elevated serum creatine
      kinase activity (normal, < or = 175 U per liter); the values were markedly
      elevated (> 900 U per liter) in 14. The MB isoenzyme of creatine kinase was
      detected in the serum of 13 of 20 patients in whom it was measured and was > or =
      4 percent of total creatine kinase activity in 6 patients. In three patients
      electrocardiography showed myocardial injury. Changes in serum creatine kinase
      activity of similar magnitude were not present in the subjects who had
      uncomplicated dives or in the patients with blunt trauma. Thirteen patients
      recovered fully, four had minor residual neurologic deficits, three were severely
      impaired, and two died. Logistic-regression analysis revealed a significant
      correlation between peak serum creatine kinase values and clinical outcome.
      CONCLUSIONS: Biochemical evidence of muscle injury is frequently found after
      diving-associated arterial gas embolism. The correlation between serum creatine
      kinase activity and outcome suggests that serum creatine kinase is a marker of
      the size and severity of arterial gas embolism.

PMID- 8259141
TI  - Computed tomographic study of the common cold.
AB  - BACKGROUND: Colds are common, but the abnormalities they produce in the nasal
      passages and sinus cavities have not been well defined. METHODS: We studied
      healthy adult volunteers with self-diagnosed colds of 48 to 96 hours' duration
      and obtained the following data: information on symptoms, computed tomographic
      (CT) studies of the nasal passages and sinuses, mucosal-transport times, measures
      of nasal-airway resistance, and viral-culture studies. Thirty-one subjects (mean
      age, 24 years) had complete evaluations, including CT scans, which were read
      without knowledge of the clinical data. An additional 79 subjects underwent the
      same evaluations, except the CT scans. RESULTS: Of the 31 subjects with CT scans,
      24 (77 percent) had occlusion of the ethmoid infundibulum; 27 (87 percent) had
      abnormalities of one or both maxillary-sinus cavities; 20 (65 percent) had
      abnormalities of the ethmoid sinuses; 10 (32 percent) had abnormalities of the
      frontal sinuses; and 12 (39 percent) had abnormalities of the sphenoid sinuses.
      Infraorbital air cells were present in 14 subjects (45 percent), and
      pneumatization of the middle turbinate (concha bullosa) was noted in 11 subjects
      (35 percent). Also common were engorged turbinates (in 7 subjects) and thickening
      of the walls of the nasal passages (in 13). After two weeks, the CT studies were
      repeated in 14 subjects, none of whom received antibiotics. In 11 of these
      subjects (79 percent) the abnormalities of the infundibula and sinuses had
      cleared or markedly improved. Nasal-airway resistance was abnormal in 29 (94
      percent) and mucosal transport in 19 (61 percent) of the 31 subjects who had CT
      scans. Rhinovirus was detected in nasal secretions from 24 (27 percent) of 90
      subjects. CONCLUSIONS: The common cold is associated with frequent and variable
      anatomical involvement of the upper airways, including occlusion and
      abnormalities in the sinus cavities.

PMID- 8259142
TI  - Images in clinical medicine. Multiple jejunoileal diverticula.

PMID- 8259143
TI  - Hemophilia A.

PMID- 8259144
TI  - Clinical problem-solving. Assembling a coherent story.

PMID- 8259145
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 1-1994. A 27-year-old woman with secondary infertility and a
      bladder mass.

PMID- 8259146
TI  - Pulmonary autograft--the optimal substitute for the aortic valve?

PMID- 8259147
TI  - Pathogenesis of "idiopathic" nephrotic syndrome.

PMID- 8259148
TI  - The risk of sudden infant death.

PMID- 8259149
TI  - The risk of sudden infant death.

PMID- 8259150
TI  - The risk of sudden infant death.

PMID- 8259151
TI  - Vesnarinone for heart failure.

PMID- 8259152
TI  - Vesnarinone for heart failure.

PMID- 8259153
TI  - Vesnarinone for heart failure.

PMID- 8259154
TI  - Hypokalemic myopathy induced by Giardia lamblia.

PMID- 8259155
TI  - Case 27-1993: cerebral vasculitis.

PMID- 8259156
TI  - Case 27-1993: cerebral vasculitis.

PMID- 8259157
TI  - Expression of transforming growth factor beta 3 in hypertrophic juxtaglomerular
      apparatus.

PMID- 8259158
TI  - Three-dimensional CT diagnosis of maxillofacial trauma.

PMID- 8259159
TI  - Three-dimensional CT diagnosis of maxillofacial trauma.

PMID- 8259160
TI  - Effect of plasma protein adsorption on protein excretion in kidney-transplant
      recipients with recurrent nephrotic syndrome.
AB  - BACKGROUND: Among patients with the idiopathic nephrotic syndrome who have focal
      and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55
      percent have recurrent nephrotic syndrome. The recurrence may be caused by a
      plasma factor or factors that increase glomerular permeability, because plasma
      exchange transiently decreases or abolishes proteinuria in some patients. We
      studied the effect on proteinuria of the removal of protein (mostly
      immunoglobulins) by adsorption onto protein A from the plasma of patients with
      recurrent nephrotic syndrome. METHODS: Eight patients were treated with one to
      three cycles of two to seven 1-day sessions of protein adsorption, and the
      patients' urinary protein excretion was measured repeatedly. Their
      immunosuppressive regimens were not changed during the treatment. The adsorbed
      proteins were eluted from the protein A and injected into rats, and the urinary
      albumin excretion of the rats was measured. RESULTS: The protein-adsorption
      treatment consistently decreased urinary protein excretion by an average of 82
      percent at the end of a cycle (P < 0.001). In one patient proteinuria
      disappeared, and in another urinary protein excretion remained below 2.5 g per
      day with repeated cycles of protein adsorption. In all but one patient the effect
      of adsorption was limited in time, with a return to the preadsorption level of
      protein excretion within a maximum of two months. The administration to rats of
      material eluted from the protein A increased urinary albumin excretion 2.9- to
      4.6-fold (P < 0.001 and P = 0.005, respectively). Although protein A primarily
      binds immunoglobulins, the active fraction of the eluted proteins had a molecular
      weight below 100,000, indicating that immunoglobulin was not directly involved.
      CONCLUSIONS: Adsorption of plasma protein decreases urinary protein excretion in
      patients with recurrence of the nephrotic syndrome after renal transplantation.
      Studies of the adsorbed proteins should provide information about the mechanism
      of this disease.

PMID- 8259161
TI  - Endometriosis.

PMID- 8259162
TI  - Vitamin K and the newborn: a correction.

PMID- 8259163
TI  - Women's health initiative.

PMID- 8259164
TI  - Health policy report. Health care reform. The states.

PMID- 8259165
TI  - Induction of graft-versus-host disease as immunotherapy for relapsed chronic
      myeloid leukemia.
AB  - BACKGROUND: The ability of allogeneic bone marrow transplantation to cure chronic
      myeloid leukemia (CML) is due to both the conditioning regimen and the
      antileukemic effects of the lymphocytes in the grafted marrow. We studied the
      ability of interferon alfa-2b and infusions of mononuclear cells from the marrow
      donor to induce a graft-versus-leukemia reaction in patients with CML in relapse
      after bone marrow transplantation. METHODS: Eleven patients with relapsed CML
      after allogeneic bone marrow transplantation were treated with interferon alfa-2b
      and infusions of mononuclear cells. The patients were monitored for toxic
      effects, for hematologic and cytogenetic responses, and, with use of the
      polymerase chain reaction, for elimination of cells containing the bcr/abl
      messenger RNA transcript characteristic of the leukemic cells. RESULTS: Six of
      the eight patients with stable CML after relapse had complete remissions
      according to molecular genetic criteria, since no cells with bcr/abl messenger
      RNA transcripts were detected (the method can identify 1 leukemic cell among 1
      million normal cells). The three patients with accelerated CML after relapse did
      not enter remission. Myelosuppression was prominent in eight patients. Grade I
      acute graft-versus-host disease (GVHD) occurred in six patients, and grade III
      acute GVHD occurred in three. Limited chronic GVHD developed in five patients.
      CONCLUSIONS: The induction of a graft-versus-leukemia reaction with interferon
      alfa-2b and infusions of donor mononuclear cells in patients with CML in relapse
      after bone marrow transplantation is an effective antileukemic therapy that may
      offer an alternative to a second marrow transplantation.

PMID- 8259166
TI  - Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz
      syndrome.
AB  - BACKGROUND: The Smith-Lemli-Opitz syndrome (frequency, 1:20,000 to 1:40,000) is
      defined by a constellation of severe birth defects affecting most organ systems.
      Abnormalities frequently include profound mental retardation, severe failure to
      thrive, and a high infant-mortality rate. The syndrome has heretofore been
      diagnosed only from its clinical presentation. METHODS: Using capillary-column
      gas chromatography-mass spectrometry, we measured the sterol composition of
      plasma, erythrocytes, lens, cultured fibroblasts, and feces from five children
      with the syndrome (three girls and two boys). RESULTS: Plasma cholesterol levels
      were abnormally low (8 to 101 mg per deciliter [0.20 to 2.60 mmol per liter]) in
      every patient, being well below the 5th percentile for age- and sex-matched
      controls. Concentrations of the cholesterol precursor 7-dehydrocholesterol
      (cholesta-5,7-dien-3 beta-ol), which was not detectable in most of our controls,
      were elevated (11 to 31 mg per deciliter) more than 2000-fold above normal and
      were similar to the levels of cholesterol in all tissues from all patients. An
      isomeric dehydrocholesterol with a structure similar to that of 7
      dehydrocholesterol was also detected. CONCLUSIONS: The combination of abnormally
      low plasma cholesterol levels and a high concentration of the cholesterol
      precursor 7-dehydrocholesterol points to a major block in cholesterol
      biosynthesis at the step in which the C-7(8) double bond of 7-dehydrocholesterol
      is reduced, forming cholesterol. The block may be sufficient to deprive an embryo
      or fetus of cholesterol and prevent normal development, whereas the incorporation
      of 7-dehydrocholesterol into all membranes may interfere with proper membrane
      function.

PMID- 8259167
TI  - Images in clinical medicine. Diaper diagnosis of porphyria.

PMID- 8259168
TI  - Pelvic inflammatory disease.

PMID- 8259169
TI  - Lactation and the risk of breast cancer.

PMID- 8259170
TI  - Interferon therapy for chronic viral hepatitis.

PMID- 8259171
TI  - Explaining the connection between privilege and health.

PMID- 8259172
TI  - Explaining the connection between privilege and health.

PMID- 8259173
TI  - Explaining the connection between privilege and health.

PMID- 8259174
TI  - Explaining the connection between privilege and health.

PMID- 8259175
TI  - Explaining the connection between privilege and health.

PMID- 8259176
TI  - Explaining the connection between privilege and health.

PMID- 8259177
TI  - Acute promyelocytic leukemia.

PMID- 8259178
TI  - Acute promyelocytic leukemia.

PMID- 8259179
TI  - Treatment for post-irradiation xerostomia.

PMID- 8259180
TI  - Treatment for post-irradiation xerostomia.

PMID- 8259181
TI  - Hepatitis C serotype and response to interferon therapy.

PMID- 8259182
TI  - Amaurosis fugax.

PMID- 8259183
TI  - Physicians' refusal to provide inappropriate treatment.

PMID- 8259184
TI  - Physicians' refusal to provide inappropriate treatment.

PMID- 8259185
TI  - Physicians' refusal to provide inappropriate treatment.

PMID- 8259186
TI  - Case 34-1993: Kaposi's sarcoma.

PMID- 8259187
TI  - Lactation and a reduced risk of premenopausal breast cancer.
AB  - BACKGROUND: The evidence of an association of lactation with a reduction in the
      risk of breast cancer among women has been limited and inconsistent. The effect
      of lactation appears to be confined to premenopausal women with a history of long
      lactation, but most studies of this relation have been limited in statistical
      power. We conducted a multicenter, population-based, case-control study with a
      sample large enough for us to describe more precisely the association between
      lactation and the risk of breast cancer. METHODS: Patients less than 75 years old
      who had breast cancer were identified from statewide tumor registries in
      Wisconsin, Massachusetts, Maine, and New Hampshire. Controls were randomly
      selected from lists of licensed drivers if the case subjects were less than 65
      years old, and from lists of Medicare beneficiaries if they were 65 through 74
      years old. Information on lactation, reproductive history, and family and medical
      history was obtained by means of telephone interviews. After the exclusion of
      nulliparous women, 5878 case subjects and 8216 controls remained for analysis.
      RESULTS: After adjustment for parity, age at first delivery, and other risk
      factors for breast cancer, lactation was associated with a slight reduction in
      the risk of breast cancer among premenopausal women, as compared with the risk
      among women who were parous but had never lactated (relative risk, 0.78; 95
      percent confidence interval, 0.66 to 0.91); the relative risk of breast cancer
      among postmenopausal women who had lactated, as compared with those who had not,
      was 1.04 (95 percent confidence interval, 0.95 to 1.14). With an increasing
      cumulative duration of lactation, there was a decreasing risk of breast cancer
      among premenopausal women (P for trend < 0.001) but not among postmenopausal,
      parous women (P for trend = 0.51). A younger age at first lactation was
      significantly associated with a reduction in the risk of premenopausal breast
      cancer (P for trend = 0.003). As compared with parous women who did not lactate,
      the relative risk of breast cancer among women who first lactated at less than 20
      years of age and breast-fed their infants for a total of six months was 0.54 (95
      percent confidence interval, 0.36 to 0.82). CONCLUSIONS: There is a reduction in
      the risk of breast cancer among premenopausal women who have lactated. No
      reduction in the risk of breast cancer occurred among postmenopausal women with a
      history of lactation.

PMID- 8259188
TI  - Treatment of chronic hepatitis D with interferon alfa-2a.
AB  - BACKGROUND AND METHODS: Chronic hepatitis D is a severe and rapidly progressive
      liver disease for which no therapy has been proved effective. To evaluate the
      efficacy of treatment with interferon, we studied 42 patients with chronic
      hepatitis D who were randomly assigned to receive either 9 million or 3 million
      units of recombinant interferon alfa-2a (three times a week for 48 weeks) or no
      treatment. RESULTS: By the end of the treatment period, serum alanine
      aminotransferase values had become normal in 10 of 14 patients receiving 9
      million units (71 percent), as compared with 4 of 14 treated with 3 million units
      (29 percent, P = 0.029) and 1 of 13 untreated controls (8 percent, P = 0.001).
      Seven patients treated with the higher dose of interferon (50 percent) had a
      complete response (normal levels of alanine aminotransferase and no detectable
      serum hepatitis delta virus [HDV] RNA), as compared with three of those who
      received the lower dose (21 percent, P = 0.118), and none of the controls (P =
      0.004). Treatment with 9 million units of interferon was associated with a marked
      improvement in the histologic findings (reduced periportal necrosis and portal
      and lobular inflammation), whereas in the untreated controls there was
      considerable histologic deterioration. In 5 of the 10 patients treated with 9
      million units of interferon whose alanine aminotransferase values became normal,
      the biochemical responses persisted for up to 4 years (mean, 39 months), but the
      effects of treatment on viral replication were not sustained. In contrast, none
      of those who received 3 million units and none of the untreated controls had a
      sustained biochemical or virologic response. CONCLUSIONS: In about half the
      patients with chronic hepatitis D treated with high doses of interferon alfa-2a
      (9 million units three times a week for 48 weeks), the serum alanine
      aminotransferase level becomes normal, HDV RNA becomes undetectable in serum, and
      there is histologic improvement. However, a relapse is common after treatment has
      been stopped.

PMID- 8259189
TI  - Acute fluoride poisoning from a public water system.
AB  - BACKGROUND: Acute fluoride poisoning produces a clinical syndrome characterized
      by nausea, vomiting, diarrhea, abdominal pain, and paresthesias. In May 1992,
      excess fluoride in one of two public water systems serving a village in Alaska
      caused an outbreak of acute fluoride poisoning. METHODS: We surveyed residents,
      measured their urinary fluoride concentrations, and analyzed their serum
      chemistry profiles. A case of fluoride poisoning was defined as an illness
      consisting of nausea, vomiting, diarrhea, abdominal pain, or numbness or tingling
      of the face or extremities that began between May 21 and 23. RESULTS: Among 47
      residents studied who drank water obtained on May 21, 22, or 23 from the
      implicated well, 43 (91 percent) had an illness that met the case definition, as
      compared with only 6 of 21 residents (29 percent) who drank water obtained from
      the implicated well at other times and 2 of 94 residents (2 percent) served by
      the other water system. We estimated that 296 people were poisoned; 1 person
      died. Four to five days after the outbreak, 10 of the 25 case patients who were
      tested, but none of the 15 control subjects, had elevated urinary fluoride
      concentrations. The case patients had elevated serum fluoride concentrations and
      other abnormalities consistent with fluoride poisoning, such as elevated serum
      lactate dehydrogenase and aspartate aminotransferase concentrations. The fluoride
      concentration of a water sample from the implicated well was 150 mg per liter,
      and that of a sample from the other system was 1.1 mg per liter. Failure to
      monitor and respond appropriately to elevated fluoride concentrations, an
      unreliable control system, and a mechanism that allowed fluoride concentrate to
      enter the well led to this outbreak. CONCLUSIONS: Inspection of public water
      systems and monitoring of fluoride concentrations are needed to prevent outbreaks
      of fluoride poisoning.

PMID- 8259190
TI  - Deutsches Institut fur Ernahrungsforschung Potsdam-Rehbrucke--a national focus
      research in human nutrition in Germany.

PMID- 8259191
TI  - Effect of freezing and mincing technique on microbial load of minced meat.
AB  - This experiment was carried out to explain the variation between the use of
      either fresh or frozen meat cuts in manufacturing of minced meat; in this
      connection the role of the mincer and the hygienic condition of handling as well
      as of the temperature under which the raw material and product was handled should
      be investigated. The achieved results indicated that the minced meat manufactured
      from fresh meat has low microbial load as compared with that produced from frozen
      one. However, the mincing at butcher's shops may expose the meat to more sources
      of contamination than that minced at home (self-made mincing). The handling of
      raw meat either fresh or frozen in butcher's shops exposed the produced minced
      meat to high numbers of either spoilage or food poisoning microorganisms. The
      sources of contamination of produced minced meat were discussed.

PMID- 8259192
TI  - Psychrotrophic bacteria in sausage.
AB  - A total of 50 samples of frozen fresh beef sausage were collected from grocery
      stores at Beni Suef City. These samples were examined for enumeration, isolation
      and identification of psychrotrophic bacteria. All samples contained
      psychrotrophic bacteria in variable numbers. The mean counts of psychrotrophic
      bacteria, psychrotrophic Enterobacteriaceae, Pseudomonas, Aeromonas, Brochothrix
      thermosphacta and Lactic acid bacteria were 2 x 10(5) +/- 10(3), 6 x 10(3) +/- 4
      x 10(2), 10(3) +/- 2 x 10(2), 4 x 10(2) +/- 8 x 10, 8 x 10(2) +/- 10(2) and 8 x
      10(2) +/- 2 x 10(2) organisms per gram, respectively. Psychrotrophic
      Enterobacteriaceae isolates were identified biochemically. The hygienic
      significance of the isolates, their public health importance as well as supposed
      measures to improve the product are discussed.

PMID- 8259193
TI  - Determination of the level of certain trace elements in vegetables in differently
      contaminated regions.
AB  - The aim of the investigations was the determination of the lead, cadmium, copper,
      iron, zinc and magnesium content in some vegetables in an industrial region
      (Cracow) and in an agricultural region far from industrial centres (control). It
      was found that all the vegetables analysed contained lead and cadmium
      contaminations. The average lead concentration in parsley-haulm and parsley-root
      and cadmium concentration in beets, onion, parsley-haulm, leek, lettuce and
      potatoes coming from the Cracow region exceeded the permissible norm. In the
      vegetables from the Cracow region the levels of the determined trace elements
      were higher (P < 0.01) than that of the controls.

PMID- 8259194
TI  - A novel metabolite of RRR-alpha-tocopherol in human urine.

PMID- 8259195
TI  - Intellectual property under GATT.

PMID- 8259196
TI  - Decriminalizing drugs?

PMID- 8259197
TI  - Newspaper ducks criticism of AIDS coverage.

PMID- 8259198
TI  - Lobbyists prompt US breast cancer campaign.

PMID- 8259199
TI  - Rival Boston hospitals set to merge.

PMID- 8259200
TI  - Pilot scheme gets go ahead for southern Europe.

PMID- 8259201
TI  - UK urged to back electronic publishers.

PMID- 8259202
TI  - Science in India.

PMID- 8259203
TI  - A model institution on trial.

PMID- 8259205
TI  - Branching out in chemical systems.

PMID- 8259204
TI  - A valve that could do good.

PMID- 8259206
TI  - GTPases. A turn-on and a surprise.

PMID- 8259207
TI  - Cell cycle. Dams and sluices.

PMID- 8259208
TI  - Plastids better red than dead.

PMID- 8259209
TI  - Proteins regulating Ras and its relatives.
AB  - GTPases of the Ras superfamily regulate many aspects of cell growth,
      differentiation and action. Their functions depend on their ability to alternate
      between inactive and active forms, and on their cellular localization. Numerous
      proteins affecting the GTPase activity, nucleotide exchange rates and membrane
      localization of Ras superfamily members have now been identified. Many of these
      proteins are much larger and more complex than their targets, containing multiple
      domains capable of interacting with an intricate network of cellular enzymes and
      structures.

PMID- 8259210
TI  - The 2.2 A crystal structure of transducin-alpha complexed with GTP gamma S.
AB  - The 2.2 A crystal structure of activated rod transducin, Gt alpha.GTP gamma S,
      shows the bound GTP gamma S molecule occluded deep in a cleft between a domain
      structurally homologous to small GTPases and a helical domain unique to
      heterotrimeric G proteins. The structure, when combined with biochemical and
      genetic studies, suggests: how an activated receptor might open this cleft to
      allow nucleotide exchange; a mechanism for GTP-induced changes in effector and
      receptor binding surfaces; and a mechanism for GTPase activity not evident from
      previous data.

PMID- 8259211
TI  - Hippocampal pyramidal cells excite inhibitory neurons through a single release
      site.
AB  - Morphologically a synapse consists of a presynaptic release site containing
      vesicles, a postsynaptic element with membrane specialization, and a synaptic
      cleft between them. The number of release sites shapes the properties of synaptic
      transmission between neurons. Although excitatory interactions between cortical
      neurons have been examined, the number of release sites remains unknown. We have
      now recorded excitatory postsynaptic potentials evoked by single pyramidal cells
      in hippocampal interneurons and visualized both cells using biocytin injections.
      Light and electron microscopy showed that excitatory postsynaptic potentials were
      mediated by a single synapse. We also reconstructed the entire axon arborization
      of single pyramidal cells, filled in vivo, in sections counterstained for
      parvalbumin, which selectively marks basket and axo-axonic cells. Single synaptic
      contacts between pyramidal cells and parvalbumin-containing neurons were dominant
      (> 80%), providing evidence for high convergence and divergence in hippocampal
      networks.

PMID- 8259212
TI  - A Drosophila homologue of human Sp1 is a head-specific segmentation gene.
AB  - Segmentation in Drosophila is based on a cascade of hierarchical gene
      interactions initiated by maternally deposited morphogens that define the
      spatially restricted domains of gap gene expression at blastoderm (reviewed in
      ref. 1). Although segmentation of the embryonic head is morphologically obscured,
      the repeated patterns of expression of the segment polarity genes reflect the
      formation of seven head segments; two of these depend on the segmentation and
      homeotic genes used in the trunk, whereas the others form as a result of the
      activity of the head-specific genes orthodenticle (otd), empty spiracles (ems)
      and buttonhead (btd). The genes ems and otd encode homeodomain proteins,
      suggesting that they may function as transcription factors. They are expressed in
      overlapping stripes in the early embryonic head of Drosophila, and their
      vertebrate homologues, otx and emx, are expressed in overlapping domains in the
      anterior central nervous system of the mouse embryo. We show here that btd is
      expressed in a stripe covering the head analgen of the segments affected in btd
      lack-of-function mutants and that btd encodes a zinc-finger-type transcription
      factor with sequence and functional similarity to the prototype mammalian
      transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd,
      a transgene providing Sp1 activity can support development of the mandibular
      segment in the head of btd mutant embryos. A ubiquitous transcription factor from
      humans can therefore replace an essential component of the genetic circuitry
      required to specify the development of a particular head segment in the fly.

PMID- 8259213
TI  - A first-generation physical map of the human genome.
AB  - Sets of ordered overlapping cloned genomic DNA fragments that span each of the
      human chromosomes are urgently needed for identification of human disease genes.
      Such a physical map also provides unique material to study the structure and
      function of the genome. We have therefore exhaustively analysed the CEPH yeast
      artificial chromosome (YAC) library, which contains 33,000 clones, whose insert
      size was individually determined. These YACs have an average length of 0.9
      megabases and cover the equivalent of 10 haploid genomes. Several mapping
      techniques were combined to provide multiple sources of structural information
      for most of these clones. Finally, the library was screened with more than 2,000
      genetic markers quasiuniformly distributed over 90% of the genome. These results
      should allow the scientific community to construct detailed maps of all human
      chromosomes. Moreover, we propose a data analysis strategy that produces a first
      generation integrated map covering most of the human genome.

PMID- 8259214
TI  - p21 is a universal inhibitor of cyclin kinases.
AB  - Deregulation of cell proliferation is a hallmark of neoplastic transformation.
      Alteration in growth control pathways must translate into changes in the cell
      cycle regulatory machinery, but the mechanism by which this occurs is largely
      unknown. Compared with normal human fibroblasts, cells transformed with a variety
      of viral oncoproteins show striking changes in the subunit composition of the
      cyclin-dependent kinases (CDKs). In normal cells, CDKs exist predominantly in
      multiple quaternary complexes, each containing a CDK, cyclin, proliferating cell
      nuclear antigen and the p21 protein. However, in many transformed cells,
      proliferating cell nuclear antigen and p21 are lost from these multiprotein
      enzymes. Here we have investigated the significance of this phenomenon by
      molecular cloning of p21 and in vitro reconstitution of the quaternary cell-cycle
      kinase complexes. We find that p21 inhibits the activity of each member of the
      cyclin/CDK family. Furthermore, overexpression of p21 inhibits the proliferation
      of mammalian cells. Our results indicate that p21 may be a universal inhibitor of
      cyclin kinases.

PMID- 8259215
TI  - A new regulatory motif in cell-cycle control causing specific inhibition of
      cyclin D/CDK4.
AB  - The division cycle of eukaryotic cells is regulated by a family of protein
      kinases known as the cyclin-dependent kinases (CDKs). The sequential activation
      of individual members of this family and their consequent phosphorylation of
      critical substrates promotes orderly progression through the cell cycle. The
      complexes formed by CDK4 and the D-type cyclins have been strongly implicated in
      the control of cell proliferation during the G1 phase. CDK4 exists, in part, as a
      multi-protein complex with a D-type cyclin, proliferating cell nuclear antigen
      and a protein, p21 (refs 7-9). CDK4 associates separately with a protein of M(r)
      16K, particularly in cells lacking a functional retinoblastoma protein. Here we
      report the isolation of a human p16 complementary DNA and demonstrate that p16
      binds to CDK4 and inhibits the catalytic activity of the CDK4/cyclin D enzymes.
      p16 seems to act in a regulatory feedback circuit with CDK4, D-type cyclins and
      retinoblastoma protein.

PMID- 8259216
TI  - Inhibition of CDK2 activity in vivo by an associated 20K regulatory subunit.
AB  - The major events of the cell division cycle are triggered by periodic changes in
      the activity of cyclin-dependent protein kinases (CDKs). In mammals, the members
      of the CDK family include CDK2 and CDC2, which are thought to be involved in the
      control of DNA replication and mitosis, respectively. The protein kinase activity
      of these enzymes is controlled by a complex array of mechanisms. Activation of
      the CDK catalytic subunit requires association with a positive regulatory subunit
      (cyclin) and phosphorylation (at Thr 160 in CDK2). This activated complex can be
      inhibited by additional phosphorylation at Thr 14 and Tyr 15. Here we report the
      identification of a new mechanism for the regulation of CDK2 activity. We find
      that CDK2/cyclin complexes in mouse fibroblasts associate tightly with a 20K
      protein (CAP20). Complexes containing CAP20 were isolated from cell lysates and
      found to have negligible kinase activity, indicating that CAP20 association in
      vivo may inhibit CDK2 activity. We purified CAP20 from 3T3 cells and found that
      low concentrations of the protein completely inhibit the kinase activity of CDK2
      in vitro. Thus CAP20 represents a new negative regulatory subunit that inhibits
      the activity of CDK2/cyclin complexes in mammalian cells.

PMID- 8259217
TI  - [Anatomical and surgical note: omental graft].

PMID- 8259218
TI  - [Prospective dose-escalation study in stereotactic radiotherapy utilizing a
      linear accelerator: report from East Hokkaido Radiosurgery Study Group (EHRSSG)].
AB  - Stereotactic radiotherapy utilizing a linear accelerator has been investigated.
      (1) Radiosurgery, (2) fractionated stereotactic radiotherapy, and (3)
      fractionated radiotherapy followed by stereotactic boost have been performed
      according to pathology, size, and prognosis of diseases. Accuracy in localization
      of the treatment center was within one millimeter using a CT simulator. From
      July, 1990 to December 1992, 69 lesions in 63 patients have been treated using
      the stereotactic radiotherapy according to prospective dose-escalation design.
      Five patients have experienced transient worsening of nerve palsy or headache,
      but these complications were self-limited. No late radiation damage was observed
      over a mean follow-up period of 12.5 months. Encouraging improvements were
      obtained in patients with metastasis, AVM, and acoustic neurinoma although the
      follow-up period was too short to be conclusive. Stereotactic radiotherapy
      utilizing a linear accelerator is thus suggested as a safe and effective approach
      providing that dose-volume-time relationship is well controlled.

PMID- 8259219
TI  - [The effect of nicardipine on internal carotid artery blood flow velocity, local
      cerebral blood flow and carbon dioxide reactivity].
AB  - To study the effect of nicardipine on the blood flow velocity of the internal
      carotid artery, on local cerebral blood flow (LCBF), and on carbon dioxide
      reactivity, an initial dose of 0.5 microgram/kg/min of nicardipine was
      administered in patients for scheduled craniotomy for cerebral aneurysm clipping
      under isoflurane anesthesia. This agent was administered until the mean arterial
      blood pressure decreased and could be maintained at about 75% of the initial
      value until the completion of aneurysm clipping. The measurements of hemodynamics
      and LCBF were performed after the exposure of the internal carotid artery (T0),
      and 10 min, 30 min after the starting of nicardipine (n = 13), (T1, T2
      respectively), before aneurysm clipping (T3) and 30 min after its discontinuation
      (T4). Local cerebral blood flow was measured by the thermal gradient blood flow
      meter. The blood flow velocity of the internal carotid artery was measured at T0
      and T3 by a 20MHz pulsed ultrasound Doppler Flow-meter under surgical microscope.
      Carbon dioxide reactivity was evaluated with % delta LCBF/delta PaCO2 (%/mmHg) at
      T0, T3 and T4. Mean arterial blood pressure decreased after nicardipine infusion.
      Local cerebral blood flow did not change during nicardipine infusion, but blood
      velocity increased significantly after nicardipine infusion from 43 +/-12 to 55
      +/- 12 cm/sec (p = 0.024). Carbon dioxide reactivity did not change after
      nicardipine infusion but had a close correlation with LCBF before (rs = 0.64, p <
      0.05), during (rs = 0.84, p < 0.01) and after hypotension (rs = 0.65, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259220
TI  - [The effect of arginine vasopressin receptor antagonist on the rat cold-injured
      brain].
AB  - Centrally released arginine vasopressin (AVP) has been reported to increase the
      water permeability of brain capillaries under both normal and pathological
      conditions. It is not known, however, whether AVP regulates the permeability of
      brain capillaries via a V1 receptor or a V2 receptor. In the present experiments,
      we attempted to suppress cold-induced brain edema with V1 or V2 receptor
      antagonists. Adult rats were intraventricularly administered with 5 ng, 50 ng, or
      500 ng of V1 receptor antagonist, or 50 ng or 500 ng of V2 receptor antagonist.
      Ten minutes after administration, a cold injury was induced in the left
      hemisphere of the brain by applying a freezing probe, which had been cooled by
      liquid nitrogen, to the left parietal skull for 20 seconds. Brain water and
      tissue sodium content were then measured 24 hours after the cold-injury. In
      experiment 1, the brain water content had significantly increased in both the
      injured and non-injured hemispheres. The administration of 50 ng of V1 receptor
      antagonist resulted in a significant reduction in the brain water content of the
      bilateral hemispheres. Administration of 50 ng of V2 receptor antagonist produced
      a significant reduction in the brain water content of the non-injured hemisphere
      only. A 500 ng administration of both antagonists did not change the brain water
      content of the bilateral hemispheres. In experiment 2, we divided the cold
      injured brain into cortical and deep structures and observed the effect of the V1
      receptor antagonist. Cold-injury induced significant increases in brain water and
      the tissue sodium content of the bilateral cortical structures, but no changes in
      bilateral deep structures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259221
TI  - [A case of spinal glioblastoma with intracranial dissemination].
AB  - A 50-year-old male developed gait disturbance and bilateral sensory disturbance
      in territories below Th 11 level in February, 1990. On February 26, 1990, an
      intradural tumor was partially removed at Th 11-12 levels, which was
      histologically diagnosed as glioblastoma multiforme; followed by post-operative
      radiotherapy (40Gy to the tumor area). CT scan of the brain was unremarkable and
      he was discharged home as ambulatory in July, 1990. Gait disturbance, occasional
      headache and vomiting developed in June, 1991. MRI revealed multiple spinal cord
      tumors at Th 11-12 and L 2-3 levels, as well as multiple intracranial tumors in
      the cerebellum, cingulate gyrus, and sylvian fissure, all of which were thought
      to be located in the cerebrospinal fluid (CSF) space. VP shunt was performed for
      hydrocephalus. MRI taken 2 months after operation demonstrated diffuse
      subarachnoid dissemination and new spinal cord tumors at C 3-4 and Th 3-10
      levels. Although pathology of the intracranial tumors was not confirmed,
      dissemination from the spinal tumor was strongly suggested by the evidence
      including the long interval after the spinal cord operation, the location of the
      multiple tumors in the CSF space, and the simultaneous intraspinal dissemination.
      Only 31 cases with intracranial dissemination from malignant spinal astrocytoma
      or glioblastoma have been reported, and, of these, most were located around the
      brainstem, cerebellum, and other regions bordering the CSF space. In malignant
      spinal cord tumor, every effort should be made to prevent CSF dissemination at
      operation or to detect it as early as possible thereafter. MRI was found to be
      the most effective method for evaluating CSF dissemination.

PMID- 8259222
TI  - [On the diploic epidermoid: report of two cases].
AB  - Primary epidermoid tumors comprise about 1% of all central nervous system
      neoplasms, although the diploic epidermoid tumor is comparatively rare. Two cases
      of diploic epidermoid tumor are reported in this paper. Case 1: A 70-year-old man
      presented with a headache. A plain craniogram showed an osteolytic lesion of the
      occipital bone with a well defined sclerotic margin. A contrast enhanced CT
      confirmed a cystic lesion with rim enhancement. On MRI, the tumor appeared
      hypointense surrounded with irregular hyperintensity on the T1WI and
      hyperintensity on the T2WI. Gd enhancement on the MRI showed no enhancement
      effect. The tumor was totally removed and cranioplasty was performed. No tumor
      invasion of the dura mater was noticed. Case 2: A 90-year-old woman presented
      with a giant tumor of the left parietal region. She noticed a painless swelling
      at the age of 20, and the tumor slowly grew over a period of 70 years. Plain
      craniogram showed a bony defect with a sclerotic margin. CT scan confirmed an
      extracranial giant tumor with destruction of the outer table under the tumor, and
      also falx meningioma. Aspiration and irrigation inside the cystic tumor were
      performed under local anesthesia. Previous authors have also said that the plain
      craniogram is characteristic and diagnostic in the case of diploic epidermoid.
      Typical round or polylobular bony defect with well defined sclerotic margins was
      visualized.

PMID- 8259223
TI  - [A case of spontaneous spinal epidural hematoma with spontaneous remission before
      surgery].
AB  - A 61-year-old man was referred to our department with spontaneously remitting
      sensorimotor disturbance and bowel and bladder dysfunctions. He had no specific
      previous history and neither received any drug nor suffered from hypertension. On
      onset, complete flaccid paralysis of lower extremities, almost complete sensory
      disturbance of all modalities below the level of Th12, and bowel and bladder
      dysfunctions were observed. MRI and CT scan revealed an epidural hematoma in the
      posterior region of the spinal cord at Th11 level. Afterwards he continued to
      improve gradually both clinically and radiologically. Four days subsequent to
      onset, on admission to our department, he had slight sensorimotor disturbance,
      and bowel and bladder dysfunctions still existed. MRI demonstrated a shrinking
      and flattened hematoma. We performed laminectomy and evacuation of the hematoma.
      Grossly and histologically, no underlying lesion was revealed. Postoperative
      course was not eventful. He was discharged without residual deficits. In our
      case, surgery accomplished three goals: definitive diagnosis, secure
      decompression and prevention of recurrence. We believe, the possibility of
      spontaneous resolution of spontaneous spinal epidural hematomas (SSEDHs) with
      spontaneous remission may be high, but prompt surgical evacuation should be the
      treatment of choice for such cases, even if no underlying lesion is revealed by
      MRI, except in cases where operative morbidity and mortality rate is high and in
      cases with no neurological deficits other than pain. A review of the literature
      indicated that not all SSEDHs with spontaneous remission resolved spontaneously
      and completely.

PMID- 8259224
TI  - [Brain metastasis of rhabdomyosarcoma with intratumorous hemorrhage: a case
      report and literature review].
AB  - A 56-year-old male suffered from primary rhabdomyosarcoma on the left internal
      thoracic wall, which was treated by chemotherapy, and local irradiation following
      biopsy. Four months after the diagnosis, he suddenly complained of headache and
      left paresthesia occurred followed by generalized convulsion and left hemiplegia.
      CT scan revealed a high density mass in the right parietal lobe. The patient was
      referred to our department and underwent emergency evacuation of the hematoma
      together with tumor removal. The pathological specimen showed spindle or oval
      like cells with hypercellularity and some mitotic figures. Immunohistochemical
      study demonstrated that many cells were positive for desmin and myoglobin, which
      is specific to myogenic tumor. These characteristics were compatible with those
      of the primary thoracic lesion, and a diagnosis of metastatic rhabdomyosarcoma
      was made. Five weeks after the craniotomy, the metastatic brain tumor recurred in
      the same site and also in the bilateral occipital lobes. Although radiotherapy to
      the brain decreased the tumor size, the patient died of respiratory failure
      eleven and a half months after the initial diagnosis. Sarcomas metastasizing to
      the brain are rare and only 16 cases of rhabdomyosarcoma metastasizing to the
      brain have been reported so far. Recent advances in chemotherapy, however, have
      been able to show the increased incidence of sarcoma metastasis to the brain.
      Therefore, the necessity of follow-up CT scan for sarcoma patients of long
      survival is to be stressed, even if the patient shows no neurological symptoms.

PMID- 8259225
TI  - [A case of intraventricular cystic meningioma].
AB  - We report a case of intraventricular cystic meningioma in the left lateral
      ventricle. A-44-year-old male patient was admitted with headache on November 25,
      1991. Neurological examination revealed acalculia and left homonymous
      hemianopsia. CT and MRI showed a solid tumor which originated in the body of the
      left lateral ventricle, and which was associated with a cystic component postero
      laterally. Tumor strains fed by the left anterior choroidal artery and the medial
      and lateral posterior choroidal artery by angiography. The tumor was totally
      removed via the lateral temporal parietal approach. Histological examination
      revealed meningotheliomatous meningioma in the solid tumor and only gliosis in
      the wall of the cyst.

PMID- 8259226
TI  - [A case of epidural hematoma caused by a vacuum extraction without any skull
      fractures and accompanied by cephalohematoma].
AB  - A case of epidural hematoma associated with cephalohematoma caused by a vacuum
      extraction was reported. Old liquefied hematoma was removed via a small burr hole
      in the parietal bone at the age of 23 days. No neurological deficits were
      recognized at the age of 6 months. As the dura mater does not easily detach from
      the overlying skull in the neonate, it is a very rare occurrence for this to
      happen as a complication of the use of forceps or in extractions. To our
      knowledge, only 4 cases of epidural hematoma after vacuum extraction have been
      reported. The mechanism of the development of an acute epidural hematoma during
      extraction is reported to be due to direct force to the dura mater and skull
      induced by negative pressure of a vacuum extraction. In the present case, it
      seems that negative pressure produced a detachment of the dura mater from the
      overlying skull. It suggests that examinations including plain craniogram and CT
      scan should be performed as soon as possible in the neonate with cephalohematoma
      when they have been delivered by a vacuum extraction.

PMID- 8259227
TI  - [A case of macrocystic cervical neurinoma diagnosed by MRI with Gd-DTPA].
AB  - The authors report a rare case of a large cystic cervical neurinoma. A 45-year
      old female was admitted to our clinic because of motor weakness of the right
      upper extremity, numbness of the right fingers and right posterior cervical pain.
      Metrizamide CT myelography demonstrated the outline of a low density mass. MRI
      showed a mass revealing low signal intensity on T1-weighted image, high signal
      intensity on T2-weighted image and marginal enhancement on contrast image with Gd
      DTPA. The mass which was diagnosed as cystic tumor, was located in the intradural
      extramedullary space between C4 to C5 segments. After C4 through C5 laminectomy,
      the tumor was found to originate from the C5 anterior motor root. The tumor
      consisted mostly of a cystic part with a very thin solid compartment beneath the
      capsule. Postoperative course of the patient was uneventful. Although spinal
      neurinoma is one of the most common spinal tumors, an almost completely
      degenerated large cystic spinal neurinoma is extremely rare. MRI with Gd-DTPA was
      useful for the diagnosis of the cystic neurinoma by clearly enhancing the margin
      of the tumor.

PMID- 8259228
TI  - [Bilateral chronic subdural hematoma with communication between the hematoma
      cavities: report of an adult case].
AB  - The authors present a case of bilateral chronic subdural hematoma with
      communication between the hematoma cavities. This 24-year-old male had hit his
      forehead while playing football and visited our hospital. An initial plain CT
      scan revealed extracerebral low density areas in the bifrontal region, which were
      considered to be post-traumatic subdural hygromas. The lesion was followed up
      with repeat CT scans. On plain CT scan performed seven weeks after the injury,
      the lesion had evolved into bilateral chronic subdural hematoma and the patient
      was admitted to our ward. He underwent burr hole drainage on the left side,
      because the hematoma volume on the left side was considerably larger than that on
      the right side. A plain CT scan on the day following the operation revealed
      complete resolution of the hematomas on both sides. A favorable re-expansion of
      the brain was confirmed on consecutive CT scan performed two months after the
      operation. In general bilateral chronic subdural hematomas in adults are
      considered to have no communication between the hematoma cavities and therefore
      they should be evacuated on both sides simultaneously. In our case, on the
      contrary, the operation revealed a communication between the hematoma cavities.
      The falx cerebri is narrow in front and this narrow anterior part is frequently
      perforated by one or more apertures. We attributed the communication to this
      anatomical feature of the falx cerebri. On preoperative CT scan, in addition, the
      inner surface of the bifrontal hematoma cavity demonstrated a smooth concave
      figure indicating retrospectively that the cavity on the left side was continuous
      with that on the right side.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259229
TI  - [Determination of myocardial risk on basis of the outcome of previous myocardial
      infarcts. Advantages of myocardial tomoscintigraphy using thallium with
      dipyridamole].
AB  - Exercise stress test, 24-hour-ambulatory electrocardiographic monitoring and
      myocardial perfusion 201-Thallium single photon emission computerized tomography
      (SPECT) with dipyridamole pharmacological stress probably have different
      sensitivities and specificities for the identification of residual ischemia after
      an acute myocardial infarction. Their clinical value is still a matter of debate.
      To comparatively evaluate various non-invasive methods, we studied 63 patients
      with previous myocardial infarction consecutively referred to our Nuclear
      Medicine Department to undergo myocardial dipyridamole (0.56 mg/kg) Thallium
      SPECT, by comparing scintigraphic results with those of the exercise stress test
      and Holter monitoring. In basal conditions, heart rate was 67 +/- 14 beats per
      minute; systolic and diastolic arterial pressures were 139 +/- 24 and 86 +/- 12
      mmHg, respectively. Following intravenous dipyridamole, heart rate rose to 84 +/-
      15 beats per minute (p < 0.0001), while systolic and diastolic pressures dropped
      to 133 +/- 26 and 79 +/- 13 mmHg, respectively (p < 0.0001; p < 0.0001). In only
      one patient with a non-Q wave myocardial infarction we did not observe any
      myocardial perfusion defect. Of 62 patients with stress perfusion defects, 53
      (85.5%) showed reversible defects and 9 (14.5%) persistent defects. Of 53
      patients with reversible defects, 29 (55%) showed defects at the infarct site, 6
      (11%) had defects outside the infarct site and 18 (34%) had defects at as well as
      outside the infarct site. Forty-two patients were examined by both exercise
      stress test and myocardial SPECT imaging: SPECT demonstrated reversible perfusion
      defects in 34 (81%) of them, whereas exercise stress test showed evidence of
      residual ischemia in 24 (57%) (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259230
TI  - [Changes in the left ventricular function in hemodialyzed patients. Role of
      Doppler echocardiography].
AB  - The aim of this study was to provide a further contribution to the study on the
      alterations of left ventricular diastolic function induced by dialysis, using
      simple indexes of diastolic function obtained with Doppler. The study is conduced
      in 15 patients with renal failure aged between 22 and 51 years old by means of
      echocardiography M-2D a pulsed Doppler analysis of the left ventricular refilling
      flow, evaluated before and after dialysis. By the results is risen up that the
      dLA has had a significant reduction (p = 0.032), the dSLV have undergone a
      reduction that is not being significant, while the dDLV has had a significant
      reduction (p = 0.029), shortening fraction is improved even if in a not
      significant manner. Also the Doppler indexes has had a behaviour homogeneous in
      the group of studied patients. Early ventricular refilling is reduced, as showed
      by the reduction of E, consequence of the reduction preload, while the diastolic
      late refilling has showed a little increment, expressed by the increase af the
      peak A. The variations of these indexes, even if not statistically significant,
      express an alteration of pattern diastolic Doppler caused by both the reduction
      of preload and the alteration of ventricular relaxation. Besides this alteration,
      to our notice, is not to consider expression of myocardial compromise in this
      group studied patients. It would be however useful enlargement of the study to
      greater number of patients with follow-up for better comprehension of this
      cardiopathy and makes a more individual treatment of these patients.

PMID- 8259231
TI  - [Doppler echocardiographic evaluation of functional parameters of mechanical and
      biological valve prostheses].
AB  - We studied and compared functional parameters in 314 valvular prostheses. The
      following parameters have been calculated: mean transvalvular gradients for
      aortic and mitral prostheses and functional area by Pht (pressure half time) for
      mitral prostheses. All patients with important depression in myocardial function,
      tachycardia or malfunctioning prostheses were excluded. 173 prostheses were in
      aortic position and 141 in mitral position. Mitral prostheses were: 31 biological
      and 110 mechanical. We subdivided mechanical prostheses in monoleaflet
      (Omnicarbon, Sorin-Carbocast and Allcarbon, Medtronic, Bjork-Shiley) and
      bileaflet (Sorin-Bicarbon, St. Jude). These three groups were compared: mean
      transvalvular gradients and area showed no differences. Aortic prostheses were:
      33 biological and 140 mechanical; mechanical prostheses were subdivided in two
      groups: monoleaflet (Sorin Allcarbon e Carbocast, Bjork-Shiley, Medtronic,
      Omnicarbon) and bileaflet (Sorin-Bicarbon, St. Jude). Mean transvalvular
      gradients of these three groups were compared within each group for every size:
      bileaflet prostheses demonstrated inferior gradients than biological and
      monoleaflet for 19-21 and 23 sizes; in superior sizes there were no significant
      differences. Further analysis showed a significant correlation among gradients
      and body surface area in the 21 size prostheses (p = 0.004). Bileaflet prostheses
      in this subgroup showed less increase in mean gradient with surface area than
      mechanical and biological ones.

PMID- 8259232
TI  - [Dynamic ECG in cerebral ischemic vasculopathies].
AB  - Fifty-four subjects suffering from TIA or Stroke underwent normal ECG and Holter
      ECG ten days after ischemic cerebral event in order to point out cardiac
      dysrhythmias as possible causes of TIA or Stroke. Holter ECG proved positive in
      70.3% of subjects versus 38.8% of normal ECG (p < 0.001). We underline the
      utility of cardiological valuation in patients suffering from TIA or Stroke in
      order to search for cardiac causes of ischemic cerebral events and to prevent
      relapses.

PMID- 8259233
TI  - [Circadian variations in the incidence of transient ischemic myocardial episodes
      during hospitalization for acute myocardial infarct].
AB  - The aim of this research was to evaluate the incidence and circadian variation of
      episodes of transient myocardial ischemia in the predischarge period after acute
      myocardial infarction (AMI). One hundred and ninety patients were selected in
      stable clinical condition, 83 with inferoposterior AMI, 61 with anterior AMI, 12
      with lateral AMI (34 patients with non Q AMI). The patients with unstable
      clinical course during the first 48 hours after admission were excluded. All
      patients underwent dynamic electrocardiography (Pathfinder 3 Reynolds Medicals)
      between the tenth and the fifteenth day of the in-hospital phase. Sixteen/190
      patients showed ECG changes due to transient myocardial ischemia, with a length
      higher than 60 sec and with an interval between episodes higher than 60 sec. Ten
      patients had ST depression, 6 patients had ST elevation. In total, the ischemic
      episodes were 25, silent 21 and symptomatic 4, with incidence from 1 to 4 during
      24 hours, with a length from 1 to 17 min (mean 8 min); mean heart rate increased
      during ischemic episodes. Seventeen/25 ischemic episodes occurred between the
      twelfth and the twenty-fourth hours. A follow-up of 15 +/- 3 months was carried
      out: 1 patient died after reinfarction, 1 patient died of non cardiac cause, 6
      patients showed unstable angina (in 4 of them myocardial revascularization
      procedure was performed), 8 patients were asymptomatic; on the contrary, 32/174
      patients without episodes of myocardial ischemia presented cardiac events, with
      lesser incidence than ischemic patients (p < 0.01). This retrospective analysis
      showed higher evidence of episodes due to transient myocardial ischemia during
      the afternoon and evening hours in the in-hospital phase after AMI.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8259234
TI  - [Monitoring the arterial pressure in the evaluation of antihypertensive therapy].

PMID- 8259235
TI  - [Age-related changes in the renin-angiotensin-aldosterone system and the
      sympathetic nervous system in patients with essential hypertension].
AB  - The aim of this study was to evaluate age, plasmatic renin activity (PRA), plasma
      aldosterone levels and the total quantity of urinary catecholamines (TOT. UR.
      CAT.) in a large population of out-patients suffering from essential arterial
      hypertension (EAH). A total of 986 patients were examined (540 women and 426 men
      aged between 15 and 87 years) suffering form slight or moderate EAH (WHO stage 1
      2). After a wash-out period of two weeks, systolic and diastolic arterial
      pressure was measured together with heart rate in clino- and orthostatism. Blood
      samples were collected to determine PRA and plasma aldosterone, and lastly a 24
      hour urine collection was made to measure the total quantity of catecholamines.
      It emerged that there was a significant increase in systolic pressure, whereas
      heart rate and PRA diminished significantly when correlated with age; diastolic
      pressure was also considerably lower, but did not reach statistical significance.
      Moreover, it was found that there was a significant positive correlation between
      PRA and TOT. UR. CAT., whereas no correlation was found between age and plasma
      aldosterone and between blood pressure and the various endocrine parameters
      examined. These data confirm the changes in the biological, hemodynamic and
      endocrine profiles observed in elderly hypertensive patients in comparison to
      young hypertensive patients, and suggests that age may be an important predictive
      factor of the activity of both the renin-angiotensin and sympathetic nervous
      system which appear to be closely connected and gradually attenuated by age.

PMID- 8259236
TI  - [Carotid endarterectomy with placement of a PUR (polyurethane) patch].
AB  - In this study, 40 patients who underwent surgery for cerebro-vascular
      insufficiency were considered. Carotid endarterectomy was the procedure of choice
      in all of the patients; the arteriotomy was always closed using a PUR patch, a
      new material that, for its chemical and physical characteristics seems to be a
      good alternative to PTFE. All of the patients underwent surgery under loco
      regional anesthesia, allowing a perioperative monitoring of the neurological
      status through the patient's active collaboration. During the postoperative
      period, non local or systemic pathology related to the use of the patch has been
      observed. During the short and half term follow-up, the patients underwent echo
      Doppler of the supra-aortic trunks that didn't show either false aneurysms or
      thrombosis on the patch surface.

PMID- 8259238
TI  - [Therapeutic interruption of pregnancy in the 4th month shortly after the patient
      underwent heart transplantation for obstructive hypertrophic heart disease].
AB  - We describe here therapeutic abortion of 16 weeks in a woman with a recently
      transplanted heart. Abortion was inevitable owing to the brief interval (4
      months) from heart transplantation, for heavy immunosuppression with risk of
      congenital anomalies, and mother's will. Abortion was procured under general
      anaesthesia and without complications. The fetus weighted 70 gm, with good
      maternal outcome.

PMID- 8259237
TI  - [Observations on a case of arterial hypertension associated with primary
      hyperparathyroidism and renal artery thrombosis].
AB  - A patient with hypertension (female: aged 48 years) associated with primary
      hyperparathyroidism and left renal artery thrombosis is described. Taking into
      account that the patient was treated on the left side by lithotripsy about two
      years before the development of hypertension while assuming an oral dose of an
      estro-progestinic compound, a possible role of these two conditions is discussed
      in the genesis of renal artery thrombosis and development of renal hypertension.

PMID- 8259239
TI  - Reviewing charts.

PMID- 8259240
TI  - Intraocular lens implantation in rural India.
AB  - We performed 379 extracapsular cataract surgeries with implantation of
      intraocular lenses (IOLs) in a public eye camp in Ganeshpuri, India (50 miles
      north of Bombay). Ninety percent (341) of the patients returned for follow up. At
      8 weeks postoperatively, 48% of the patients had a visual acuity of 6/18 or
      better uncorrected; with correction, this figure rises to 71.5%. In general,
      surgical complications were neither severe nor frequent. More serious
      difficulties were associated with measuring initial IOL power, obtaining
      refractive data (including astigmatism), follow up of astigmatism (suture
      cutting), posterior capsule opacification, and associated preoperative pathology.
      On the basis of our data, we believe that IOL implantation in public eye camps,
      under controlled conditions of asepsis and with appropriate instrumentation, is a
      safe and effective way to provide visual rehabilitation to the rural populations
      of third-world countries.

PMID- 8259241
TI  - Topical fluorometholone reduces stromal inflammation after photorefractive
      keratectomy.
AB  - To examine the effectiveness of topical steroids in decreasing corneal stromal
      inflammation induced by photorefractive keratectomy, four rabbits underwent
      uniocular corneal deepithelialization, or deepithelialization followed by
      photorefractive keratectomy. Topical fluorometholone acetate 0.5% was applied
      topically to half of the eyes after photorefractive keratectomy.
      Polymorphonuclear leukocytes (PMNs) were counted 24 hours after surgery. The
      number of PMNs in the corneal stroma was significantly higher after
      photorefractive keratectomy than after deepithelialization alone (P = .001) and
      than in normal unoperated corneas; fluorometholone treatment significantly
      reduced PMN accumulation (P = .001). Photorefractive keratectomy in rabbits
      induces an intense inflammation of the superficial stroma that can be effectively
      treated with topical fluorometholone. A short course of topical corticosteroids
      may, therefore, be appropriate after excimer laser surgery in humans.

PMID- 8259242
TI  - Delayed sustained increase in intraocular pressure secondary to the use of
      polyacrylamide gel (Orcolon) in the anterior chamber.
AB  - Orcolon, a new viscoelastic substance, was withdrawn from the market in the
      United States by the manufacturer (Optical Radiation Corporation [ORC], Azusa,
      Calif) because of reports of delayed sustained increases in intraocular pressure
      (IOP) observed in patients who had undergone anterior segment surgery involving
      the use of this product. We examined the charts of 118 cases of anterior segment
      surgery involving Orcolon at our institution and found delayed IOP spikes in 20
      of the 116 cases that had at least 3 months of follow up. Procedures included
      cataract extraction, penetrating keratoplasty, secondary intraocular lens
      implantation, and glaucoma surgery. Response to maximal medical therapy was poor;
      11 patients underwent procedures for IOP control, an additional 4 required new or
      increased medications, and 3 developed persistent iritis, which required
      steroids. Four patients lost two or more lines of Snellen line chart visual
      acuity, and one went from counts fingers to light perception. The cause may be
      related to the presence of small particles of viscoelastic, which could lead to
      decreased aqueous outflow, particularly in eyes with an already compromised
      trabecular meshwork.

PMID- 8259243
TI  - Trabeculotomy in juvenile primary open-angle glaucoma.
AB  - Long-term results of trabeculotomy in juvenile primary open-angle glaucoma
      (JPOAG) were investigated based on a follow-up study of 16 eyes in 11 patients,
      diagnosed when they were between 10 and 45 years old. Preoperative visual field
      defects were found in 75% (12/16) of the eyes. After a mean follow up of 7 years
      (range, 1 to 18 years), 88% (14/16) of the eyes had an intraocular pressure (IOP)
      of 21 mm Hg or less (peak pressure at diurnal curves). Nine of these were
      receiving no medical treatment and five were being treated with beta-blockers
      and/or dipivefrin. The best results were in the younger patients; the success
      rate of those under age 40 years was 100%. After normalization of IOP, visual
      field testing showed no progression in defects. We conclude that trabeculotomy
      rather than filtering surgery should be used to treat JPOAG, because the success
      rate of filtering surgery decreases with decreasing age. Also, the good
      functional results achieved in these patients after normalization of IOP may
      indicate that ocular hypertension is the only risk factor in JPOAG.

PMID- 8259244
TI  - Trabeculectomy with 5-fluorouracil vs single-plate Molteno implantation.
AB  - We compared the results achieved in 22 consecutive patients who underwent single
      plate Molteno implantation, with those achieved in a matched group who had
      trabeculectomy with postoperative 5-fluorouracil. Six months following surgery,
      the average intraocular pressure (IOP) in the Molteno group was 15.4 +/- 8.0 mm
      Hg, and in the trabeculectomy group, 16.1 +/- 5.6 mm Hg (P = .920). A mean of 1.4
      antiglaucoma medications were being used in each group (P = .776). Complications
      following Molteno implantation included six tube revisions and three flat
      anterior chambers; following trabeculectomy, eight serous choroidal detachments
      and nine positive Seidel tests. This study suggests that Molteno implantation and
      trabeculectomy with adjunctive 5-fluorouracil provide similar IOP control, but
      that the two procedures are associated with different types of complications.

PMID- 8259245
TI  - 5-FU-supplemented phacoemulsification, posterior chamber intraocular lens
      implantation, and trabeculectomy.
AB  - I reviewed the charts of 129 consecutive patients: 38 of whom underwent 5
      fluorouracil (5-FU)-supplemented, combined phacoemulsification, posterior chamber
      lens implantation, and trabeculectomy (phaco/5-FU group); 55 of whom underwent
      the same combined procedure without 5-FU (phaco group); and 36 of whom underwent
      a similar combined procedure in which extracapsular cataract surgery was
      performed instead of phacoemulsification, again without 5-FU (ECCE group). I
      evaluated and compared the surgical results in these three groups at several
      points, up to and including 1 year postoperatively, in terms of intraocular
      pressure (IOP), number of antiglaucoma medications being used, presence or
      absence of a visible filtering bleb, visual field, anterior chamber cell and
      flare, visual acuity, postoperative induced astigmatism, and incidence of cystoid
      macular edema. At 3 months and beyond, there were more blebs in the phaco/5-FU
      group than in the phaco or ECCE groups. IOPs were generally lowest in the phaco/5
      FU group, as were the number of antiglaucoma medications being used. There was no
      significant difference in the distribution of the amount of visual field loss
      among the three groups. Inflammation was generally least in the phaco/5-FU group,
      but there was no significant difference among the groups in terms of
      postoperative-induced astigmatism and visual acuity. I conclude that 5-FU
      supplemented phacoemulsification combined surgery is safe and probably produces
      better filtering results than those achieved without the adjunctive use of 5-FU.

PMID- 8259246
TI  - Perfluoroperhydrophenanthrene (Vitreon) as a short-term vitreous substitute after
      complex vitreoretinal surgery.
AB  - Forty-one eyes underwent surgery for complex vitreoretinal disease, with
      perfluoroperhydrophenanthrene (Vitreon) used as an intraoperative tool and
      postoperative vitreous substitute. Postoperative use of Vitreon ranged from 3
      days to 9 weeks (mean, 3.3 weeks). All retinas were reattached intraoperatively;
      73% remained attached after the initial surgery. The final macular attachment
      rate was 100% after additional surgery. Four eyes that received a combination of
      Vitreon and silicone oil for simultaneous superior and inferior tamponade were
      successfully reattached after the initial procedure. Visual acuity improved or
      remained stable in 80% of the eyes. No toxic effects directly attributable to
      Vitreon were observed. Mean follow up was 9 months.

PMID- 8259247
TI  - Capillary hemangioma of the optic disc associated with a total retinal
      detachment.

PMID- 8259248
TI  - The "lock-and-valve" incision: truce in the "suture wars".
AB  - We describe a variation of the "classical" cataract incision that uses midsize
      incisions and standard instrumentation. Perpendicular entrance and oblique cut
      create an acute angle with the iris plane, generating an intracorneal valve. This
      results in better apposition of the wound's lips and less responsiveness to
      variations in intraocular pressure; thus, fewer stitches are required. We have
      achieved favorable results in 16 patients using this type of incision.

PMID- 8259249
TI  - Failed dacryocystorhinostomy: the sump syndrome.
AB  - A dacryocystorhinostomy may fail due to a problem along the canaliculus, at the
      ostomy site of nasolacrimal sac to nose, due to an intranasal problem or related
      to the stent. The "sump syndrome" occurs when a residual nasolacrimal sac forms,
      collects fluids, and leads to tearing. This entity, although uncommon, has a
      characteristic clinical history and radiologic appearance.

PMID- 8259250
TI  - Upper eyelid retraction after retinal detachment repair.
AB  - Two patients with high myopia developed unilateral upper eyelid retraction after
      retinal detachment surgery with superiorly placed scleral buckles and 360-degree
      encircling elements. The isolated upper eyelid retraction was stable for 16 and
      23 years, respectively. Other common causes of eyelid retraction, including
      cicatricial processes such as thyroid-related orbitopathy, neurogenic disease,
      and pseudoretraction of the eyelid, were excluded in both patients. The first
      patient had no evidence of proptosis or lid lag on downgaze but had exposure
      keratitis that required recession of Muller's muscle and conjunctiva. The second
      patient had lid lag on downgaze, and orbital computed tomography demonstrated an
      enlarged eye with an encircling element that caused mild pseudoproptosis. This
      patient required no treatment. The unilateral upper eyelid retraction did not
      progress in either patient. Although the exact mechanism of the upper eyelid
      retraction in these two cases is unclear, previous retinal surgery that involves
      superiorly placed implants must be considered in the differential diagnosis of
      unilateral upper eyelid retraction, especially when the patient has a history of
      pathologic myopia.

PMID- 8259251
TI  - A refined technique of transscleral suture fixation of posterior chamber lenses
      developed for cases of complicated cataract surgery with vitreous loss.
AB  - Described is a new technique of transscleral suture fixation of posterior chamber
      intraocular lenses (PC-IOLs) designed to simplify the procedure in cases of
      complicated cataract surgery with vitreous loss. Sling-sutures are hooked to both
      haptics of the PC-IOL and the transscleral sutures are buried in scleral tissue
      without scleral flaps. This scleral-slit technique, which has been successfully
      used in 20 patients, provides a useful alternative, even in destabilized eyes, to
      techniques that require preparation of scleral flaps.

PMID- 8259252
TI  - A technique for knotting a suture around the loops of a dislocated intraocular
      lens, within the eye, for fixation in the ciliary sulcus.
AB  - I describe a new, simpler, technique for attaching a suture to the haptic of a
      dislocated posterior chamber lens implant. A 10-0 polypropylene suture is used,
      doubly armed with straight needles. This technique has been used successfully in
      five cases.

PMID- 8259253
TI  - Minimizing conjunctival wound leaks in filtration surgery with mitomycin C.

PMID- 8259254
TI  - Photographic documentation of lacrimal obstruction.

PMID- 8259255
TI  - A simple, useful improvement of an eye protector.

PMID- 8259256
TI  - Health care policy: marginal vs average cost reimbursement.

PMID- 8259257
TI  - Inadvertent cyclodialysis cleft.

PMID- 8259258
TI  - Combined cataract/glaucoma procedures in patients on chronic miotics.

PMID- 8259259
TI  - Returning to family practice.

PMID- 8259260
TI  - Effect of epinephrine on local partial pressure of oxygen in the ciliary
      processes.
AB  - Local pO2 was measured close to the ciliary process of the rabbit eye using
      polarographic microelectrodes under microendoscopic observation. The experiments
      were performed in 5 anaesthetized New Zealand rabbits. Changes in local pO2,
      intraocular pressure (IOP) and blood flow velocity (BFV) were investigated after
      intra-arterial and topical application of epinephrine. After intra-arterial
      epinephrine, a simultaneous decrease in BFV, IOP and local pO2 was found. pO2
      decrease was more pronounced in the anterior part of the ciliary processes than
      in the posterior part. Topical epinephrine lead to similar changes of all
      parameters mentioned above, the time constants being 10-20 times longer. In these
      topical experiments, no recovery of local pO2 was found over a period of at least
      30 min despite an increase in BFV. Our results indicate that in the hyperemic
      phase after epinephrine the activity of the ciliary epithelium (and probably the
      total aqueous formation) is higher than normal. Thus, the decrease in IOP in this
      phase must be due to an increased outflow facility.

PMID- 8259261
TI  - Epiretinal membrane of proliferative diabetic retinopathy: an immunohistochemical
      study.
AB  - Nineteen cases of epiretinal membrane (ERM) in proliferative diabetic retinopathy
      were studied using immunohistochemical methods. Antibodies against type I-IV
      collagen, fibronectin (FN), glial fibrillary acidic protein (GFAP), vimentin and
      the monoclonal antibody (MAB) against human Muller cells were used to examine the
      membranes. Type II collagen was found on one side of the ERMs in 95% of the
      cases. The other types of collagen, FN and vimentin were also identified in most
      cases. Muller cells (GFAP- and MAB-positive) were found in 2/19 cases (11%), and
      astrocytes (GFAP-positive but MAB-negative) were found in 10/19 cases (53%).
      These results suggest that type II collagen (vitreal collagen) may act as a
      scaffolding in the formation of ERMs and that glial elements of the ERMs consist
      mainly of astrocytes.

PMID- 8259262
TI  - Stability of normal and aging lens gamma crystallins.
AB  - Fluorescence polarization and near UV circular dichroism (CD) studies were
      performed on four purified human gamma crystallin fractions derived from normal
      (eye bank lenses) ranging in age from the first decade through the seventh
      decade. All the four young (first decade) gamma crystallins had higher
      polarization values compared with the old (sixth and seventh decade) fractions:
      in addition, the CD spectra of the gamma I and II crystallins show substantial
      aging differences; marked decrease in intensity of the negative tryptophan band
      near 290 nm. While this effect is much less pronounced in the gamma III and IV
      fractions, aging changes in other areas of some of these fractions also occur.
      These data demonstrate significant alterations occurring in the human gamma
      crystallins associated with the normal aging process. Specific conformational
      alterations are proposed to account for these changes.

PMID- 8259263
TI  - Efficacy of intravitreous interleukin-1 in the reabsorption of experimental
      vitreous hemorrhage in rabbits.
AB  - A low degree of phagocytosis in the vitreous is considered a major cause of the
      inadequate spontaneous removal of vitreous hemorrhage. We investigated the
      putative role of natural human interleukin-1 (IL-1) in the clearance of
      experimental vitreous hemorrhage and compared it with that of retinal
      cryotherapy. Five groups of 10 albino rabbits each were injected intravitreously
      with 0.1 ml autologous whole blood. Mean fundus revisualization times after blood
      clouding were as follows: group 1 controls (blood injection and no further
      manipulation), 6.1 weeks; group 2 (transconjunctival cryoapplication 7 days after
      blood injection), 4.3 weeks; group 3 (natural human IL-1 injected into the
      vitreous 7 days after blood injection), 3.8 weeks; group 4 (cryoapplication and
      IL-1 seven days after blood injection), 3.7 weeks; group 5 (intravitreous
      injection of phosphate-buffered saline), 4.1 weeks. Differences were
      statistically significant at week 4 of follow-up (p < 0.01). Two additional
      groups were used to estimate the possible toxicity of IL-1 (group 6) and PBS
      (group 7). Clinical and histologic examinations found no intraocular alterations
      imputable to IL-1. These results suggest that IL-1 may be used for nonsurgical
      treatment of human vitreous hemorrhage.

PMID- 8259264
TI  - Ocular fluid ferning test and fractals.
AB  - The ferning test can be regarded as a crystallization process obtained by simple
      water subtraction. Such a process is feasible for every kind of ocular fluid
      (i.e. tears and aqueous, vitreous and subretinal fluids). The ferning test can be
      described in terms of fractal geometry, as the image characteristics related to
      this test are consistent with three of the main properties of fractals: self
      similarity, fractal dimension and lacunarity.

PMID- 8259265
TI  - Prevention of chloroquine-induced electroretinographic damage by a new platelet
      activating factor antagonist, BN 50730.
AB  - Chloroquine retinopathy is a severe toxic retinal impairment which may result in
      loss of vision by alterations of the retinal pigment epithelium and
      photoreceptors. Currently, there is no specific treatment for this retinopathy.
      Platelet-activating factor (PAF) is known to modulate retinal function and is one
      of the major immunomediators of the retina. In order to test the possible
      involvement of PAF in chloroquine-induced retinopathy and the effectiveness of
      PAF antagonists in the prevention of this condition, we investigated the effects
      of BN 50730, a specific PAF antagonist, on the electroretinogram (ERG) of the
      isolated rat retina exposed to chloroquine. When retinas from normal rats were
      perfused with chloroquine (10(-6) M), a marked and rapid decrease in b-wave
      amplitude was observed. In contrast, chloroquine had no effect on the b-wave of
      the retina isolated from animals pretreated with the PAF antagonist BN 50730 (30
      mg/kg/day, i.p., for 5 days). The results obtained indicate that (i) chloroquine
      is a toxic drug for retinal function, (ii) PAF plays a key role in the mediation
      of chloroquine retinopathy and (iii) PAF antagonists may constitute valuable
      agents for the treatment of this retinal impairment.

PMID- 8259266
TI  - Facial parasympathetic innervation of the rat choroid, lacrimal glands and
      ciliary ganglion. An ultrastructural pterygopalatine tracing and
      immunohistochemical study.
AB  - The pterygopalatine parasympathetic innervation of the rat choroid, lacrimal
      glands and ciliary ganglion was ultrastructurally studied by anterograde 3H
      leucine tracing. Numerous unmyelinated fibers and vesicle-containing terminals
      were labeled in these structures. No direct synaptic contacts were found. In the
      choroid, similar terminals were immunoreactive to vasoactive intestinal
      polypeptide (VIP). A regulatory feedback loop within the eye-related peripheral
      nervous system is endorsed by the present results. The finding of fibers and
      terminals of pterygopalatine origin in the lacrimal glands agrees with earlier
      studies in cats and monkeys. In the ciliary ganglion, pterygopalatine terminals
      most likely influence the ganglion cells by nonsynaptic release of
      neurotransmitters or neuromodulators including VIP.

PMID- 8259267
TI  - Treatment of experimental acute corneal inflammation with inhibitors of the
      oxidative metabolism.
AB  - The authors studied the effect of topical 2% 6-aminonicotinamide and 0.1%
      adenosine on an experimental model of acute corneal inflammation. Luminol
      enhanced chemiluminescence (LAC), as an indirect measurement of free-radical
      release, and computer-assisted planimetry of the corneal ulcer and its infiltrate
      were performed both ex vivo and in vivo on the fifth day following the induction
      of experimental alkali burn keratitis. The authors proved that both drugs
      significantly inhibited LAC both ex vivo and in vivo and that such treatments had
      also a significant beneficial effect on the evolution of the corneal ulcer and
      its infiltrate. To the best of the authors' knowledge, this finding had not been
      previously reported in experimental corneal inflammation and may indicate that
      treatment with inhibitors of the oxidative metabolism could offer a new approach
      in the pharmacological modulation of acute corneal inflammation.

PMID- 8259268
TI  - Ophthalmic complications of crack cocaine.

PMID- 8259269
TI  - Suprachoroidal hemorrhage.

PMID- 8259270
TI  - Demystifying the peer review process.

PMID- 8259271
TI  - Timing of amblyopia therapy relative to strabismus surgery.
AB  - BACKGROUND: It is taught that amblyopia must be fully reversed before surgery for
      esotropia is undertaken to achieve the best surgical outcome. In some cases, this
      means delaying surgery for many months. The alternative of operating early,
      before the completion of amblyopia therapy, and continuing to treat the amblyopia
      postoperatively has not been evaluated previously. METHODS: Forty-seven children
      younger than 8 years of age were identified with a history of both amblyopia and
      esotropia. They had no other ocular, medical, or neurologic abnormalities. They
      had no prior strabismus surgery. Of these 47 patients, 26 had their amblyopia
      fully treated before surgery, and 21 underwent surgery before completing
      amblyopia therapy. Five of the latter group did not require amblyopia therapy
      after surgery even though they were still amblyopic before operation. The motor
      outcome was assessed by comparing the motor alignment at 6 and 0.33 m using
      accommodative targets in primary position before surgery, at 6 months after
      surgery, and at the child's most recent visit. Motor success was defined in this
      study as a postoperative deviation at distance fixation of 8 prism diopters or
      less. The sensory result was assessed by comparing the frequency of detectable
      stereoacuity. RESULTS: The treatment groups did not differ significantly in age,
      depth of amblyopia, refractive error, or preoperative angle. There was no
      significant difference detected in motor or sensory outcome whether amblyopia was
      fully or only partially treated before surgery. CONCLUSION: Performing corrective
      surgery in children with esotropia before full resolution of amblyopia is safe
      and efficient if the amblyopia therapy is continued after surgery. This strategy
      permits earlier surgery without postponing the operation until full resolution of
      amblyopia. The finding that five patients did not require amblyopia therapy after
      surgery suggests that eye re-alignment itself can help reverse amblyopia in some
      cases.

PMID- 8259272
TI  - Ocular pathology of MELAS syndrome with mitochondrial DNA nucleotide 3243 point
      mutation.
AB  - PURPOSE: The authors describe the clinical, histopathologic, and ultrastructural
      findings in two eyes obtained at autopsy from a 21-year-old woman with
      mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS
      syndrome). METHODS: The eyes were obtained immediately after death. The right eye
      was fixed in 10% neutral-buffered formalin and processed for standard histologic
      examination. The left eye was fixed in a neutral-buffered 2.5% glutaraldehyde
      solution and processed for transmission electron microscopic examination. The
      authors compared the histologic and ultrastructural findings with the clinical
      features recorded photographically. RESULTS: The main clinical ophthalmologic
      features were bilateral ptosis, chronic external ophthalmoplegia, diffuse
      choroidal atrophy, atypical pigmentary retinopathy with macular involvement, and
      patchy atrophy of the iris stroma. Molecular genetic analysis detected a tRNA Leu
      (UUR) point mutation at position 3243 of mitochondrial DNA (MELAS genotype).
      Results of histologic and ultrastructural examination showed ragged-red fibers in
      the rectus muscles, degeneration of photoreceptor outer segments in the macula,
      hyperpigmentation and atrophy of the retinal pigment epithelium of the macula,
      atrophy of the iris stroma, early posterior subcapsular cataract, and optic
      atrophy. The retinal pigment epithelium, inner segments of the photoreceptors,
      smooth muscle cells of the choroidal and retinal vessels, the dilator and
      sphincter muscle of the iris, cornea, lens epithelium, and ciliary epithelium all
      contained many, often enlarged, structurally abnormal mitochondria with
      occasional paracrystalline inclusions and circular cristae. CONCLUSIONS: The
      MELAS-associated mitochondrial DNA nucleotide 3243 point mutation can cause a
      spectrum of ocular signs and symptoms that may be dependent on the patient's age
      and the amount of mutant mitochondrial DNA in the tissue. MELAS syndrome should
      be considered in the differential diagnosis of bilateral ptosis, external
      ophthalmoplegia, and atypical pigmentary retinopathy with macular involvement.

PMID- 8259273
TI  - Ocular anomalies in the alagille syndrome (arteriohepatic dysplasia).
AB  - BACKGROUND: The Alagille syndrome (arteriohepatic dysplasia) is a well-recognized
      multiple malformation syndrome consisting of a paucity of intrahepatic bile bile
      ducts, peripheral pulmonary artery hypoplasia with variable cardiac
      abnormalities, cholestatic facies, butterfly-like vertebral arch defects, and
      variable ocular anomalies, most commonly posterior embryotoxon and pigmentary
      retinopathy. METHODS: The authors studied ocular findings in six patients from
      two families with Alagille syndrome to characterize more fully the spectrum of
      ocular anomalies in this disorder. RESULTS: Ocular anomalies consisted of a
      peculiar mosaic pattern of iris stromal hypoplasia in all patients, posterior
      embryotoxon and microcornea in five patients, anomalous optic discs in five
      patients, regional peripapillary retinal depigmentation in three patients, and a
      congenital maculopathy in one patient. CONCLUSION: The Alagille syndrome
      comprises a broad spectrum of ocular anomalies involving the cornea, iris,
      retina, and optic disc. In the setting of neonatal cholestasis, the findings of
      microcornea, posterior embryotoxon, mosaic iris stromal hypoplasia, regional
      peripapillary depigmentation, congenital macular dystrophy, and anomalous optic
      discs should suggest the diagnosis of Alagille syndrome.

PMID- 8259274
TI  - Sex hormones and the incidence of severe retinopathy in male subjects with type I
      diabetes.
AB  - BACKGROUND: Diabetic retinopathy rarely occurs before puberty, suggesting that
      changes in sex hormones may influence the development of this condition. METHODS:
      The authors measured total testosterone, free testosterone, sex hormone-binding
      globulin, estradiol, and dehydroepiandrosterone-sulfate levels in 44 men with
      type I diabetes participating in the 1984 to 1986 re-examination phase of the
      Wisconsin Epidemiologic Study of Diabetic Retinopathy, a population-based study
      of diabetic complications. The mean age was 32.7 years, and the mean duration of
      diabetes was 15.4 years. Subjects who progressed to proliferative or
      preproliferative retinopathy 6 years later (cases, n = 22) were compared with
      subjects who had little or no progression (controls, n = 22). Both groups were
      matched on initial level of retinopathy. Seven stereoscopic retinal photographs
      of each eye were obtained at both examinations, and the photographs were read by
      the University of Wisconsin Reading Center. RESULTS: Sex hormone-binding globulin
      concentrations (nmol/l) were significantly lower (reflecting increased
      androgenicity) in cases than in controls (22.4 +/- 11.4 versus 32.5 +/- 19.8; P =
      0.04). No other statistically significant differences in hormone levels were
      observed. CONCLUSION: Neither serum testosterone nor other sex hormones were
      related to the incidence of severe retinopathy. The relationship to low-serum sex
      hormone-binding globulin suggests that increased androgenicity may be associated
      with the progression of retinopathy in male subjects with type I diabetes.

PMID- 8259275
TI  - Retreatment of full-thickness macular holes persisting after prior vitrectomy. A
      pilot study.
AB  - PURPOSE: Vitrectomy with fluid-gas exchange has been shown to close more than one
      half of full-thickness macular holes, with improvement in visual acuity. By
      adding the appropriate dose of transforming growth factor-beta 2, a higher
      success rate has been reported. However, there still remain cases of macular
      holes that fail to close after vitreous surgery. The current pilot study is
      designed to determine whether reoperation may have a role in the management of
      cases that fail after vitreous surgery. METHODS: Twelve eyes with persistent full
      thickness macular holes that failed to close after an initial vitrectomy
      underwent reoperation using 1330 ng transforming growth factor-beta 2. RESULTS:
      After the second operation, closure occurred in 12 (100%) of 12 eyes. Follow-up
      ranged from 8 to 16 months. Visual acuity also improved by two or more lines in 5
      (42%) of 12 patients. Increased nuclear sclerosis occurred in nine (90%) of the
      ten phakic eyes. Of the five eyes showing visual improvement, four required
      cataract extraction and intraocular lens implantation. CONCLUSION: Retreatment of
      persistent full-thickness macular holes with transforming growth factor-beta 2
      appears to have a beneficial effect on both neurosensory retinal flattening and
      visual outcome.

PMID- 8259276
TI  - Ocular manifestations of adult T-cell leukemia/lymphoma. A clinicopathologic
      study.
AB  - BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a recently described
      distinct clinicopathologic entity characterized by an extremely aggressive
      clinical course, a leukemic or lymphomatous proliferation of hyperlobulated
      peripheral T cells, and an association with infection by a retrovirus, human T
      lymphotropic virus type I (HTLV-I). The authors present a patient with ATLL who
      initially had clinical features of severe uniocular intraocular inflammation,
      simulating acute retinal necrosis or herpetic retinitis, but results of
      histopathologic examination of the globe showed ATLL. PATIENT: A 38-year-old man
      had severe unilateral intraocular inflammation associated with widespread diffuse
      retinitis. Two weeks later, a focal retinitis with vasculitis developed nasal to
      the optic disc in the opposite eye. Shortly thereafter, mental disturbance
      developed, and the patient died less than 3 months after onset of the ocular
      symptoms. RESULTS: Results of postmortem examination showed atypical lymphocytic
      infiltration in the eyes, brain, and other systemic organs. Results of
      histopathologic and immunohistochemical studies showed that the atypical cells
      infiltrating the ocular tissues were ATLL cells. CONCLUSIONS: Patients infected
      with HTLV-I initially can have intraocular T-cell lymphoma that simulates acute
      retinal necrosis or herpetic retinitis.

PMID- 8259277
TI  - Quantitative grading of nerve fiber layer photographs.
AB  - PURPOSE: The authors have developed a simple method for semi-quantitative grading
      of atrophy of the peripapillary nerve fiber layer (NFL) in black and white
      photographs. METHODS: An experienced observer read sets of NFL photographs using
      a four-level grading system. Five observers with varying levels of experience at
      ophthalmic examination were taught the grading system in approximately 4 hours,
      and their readings were compared with those of the expert. RESULTS: The
      reproducibility of readings by an experienced observer was excellent. The
      validity of the grading system was confirmed by comparisons to visual field
      findings, as well as to cup-to-disc ratios in the same eyes. The agreement with
      the expert by the five trained graders was good. CONCLUSIONS: Grading of the NFL
      could be useful both to monitor development of early glaucoma damage clinically
      and to measure progression of glaucoma damage in clinical trials research. The
      grading system can be taught readily to other observers.

PMID- 8259278
TI  - Visual field defects in normal-tension and high-tension glaucoma.
AB  - BACKGROUND: Differences in visual field characteristics between normal-tension
      glaucoma (NTG) and high-tension glaucoma (HTG) have not been established. This
      study re-examined the problem by pointwise between-group comparison of data
      obtained with the Humphrey 30-2 program. METHODS: Sixty-eight NTG cases with
      maximum intraocular pressure (IOP) of 21 mmHg or lower and 62 HTG cases with
      maximum IOP of 25 mmHg or greater with a mean deviation (STATPAC) greater than 
      10 decibels (dB) were included. Age, refraction, mean deviation, or sex ratio
      were matched between the two groups. Total deviation (STATPAC), the difference
      between the measured threshold and the age-corrected normal reference at each
      test point of the 30-2 program, was used for pointwise between-group comparisons.
      Another parameter, total deviation - mean total deviation, was introduced to
      normalize the total deviation by the overall visual field damage as an index of
      disease stage. Mean total deviation is the average of total deviations across the
      test field. Further, logistic discriminant analysis was applied to confirm that
      the difference at a questioned test point was due to the difference of disease
      type, but not disease stage, between the two groups. RESULTS: Comparison using
      total deviation and total deviation - mean total deviation gave similar results,
      which were collaborated by logistic discriminant analysis. For a given amount of
      visual field damage, an area just above the horizontal meridian was significantly
      more depressed in NTG, while HTG had significantly more diffuse visual field
      damage. CONCLUSION: Visual field defect of NTG differs from that of HTG, which
      may suggest that different regions of the optic disc are more susceptible to
      damage in NTG.

PMID- 8259279
TI  - Ocular aspergillosis isolated in the anterior chamber.
AB  - BACKGROUND: In all cases in which ocular involvement has been reported in
      endogenous aspergillosis, the posterior segment of the eye was involved. METHODS:
      The authors examined a patient who had been intubated and treated with
      corticosteroid therapy for status asthmaticus and in whom a mass later developed
      in the anterior chamber of the right eye. RESULTS: Computed tomography showed a
      solitary lesion in the left lower pulmonary lobe and multiple brain lesions that
      enhanced with contrast. Aspergillus fumigatus was cultured from the endotracheal
      tube. However, ocular and blood cultures were negative, as were the results of a
      bone marrow biopsy, lung biopsy, and anterior chamber paracentesis. Disseminated
      aspergillosis was confirmed when a biopsy of the anterior chamber mass was
      performed, and results of histopathologic examination showed the presence of
      hyphae. The patient responded to a regimen of antifungal drugs. CONCLUSION: This
      is the first known reported case in which the diagnosis of disseminated
      aspergillosis was confirmed with biopsy of an anterior chamber mass. This case
      demonstrates that Aspergillus organisms may disseminate to the anterior chamber
      of the eye without involving the posterior segment.

PMID- 8259280
TI  - Corneal endothelial cell loss induced by air bags.
AB  - BACKGROUND: Although the automobile air bag is a safety device used to protect
      drivers from death and moderate-to-severe injury, recently it also has been
      reported to be associated with some ophthalmic injuries. The authors have
      encountered a case in which a normal air bag may have caused a driver's corneal
      endothelial cell loss. In this study, the authors evaluate corneal endothelial
      cell loss caused by several types of air bags in the hope that air bag technology
      may be improved. METHODS: The authors performed impact tests with whole pig eyes
      fixed in a crash test dummy, using five different types of air bags. The area of
      damaged corneal endothelial cell was analyzed quantitatively. RESULTS: The
      authors found that corneal endothelial cell loss was correlated with the inflator
      power of the air bag but not with its weight. CONCLUSION: Although greater
      inflator power is needed for rapid air bag expansion, the effect on the eye
      should be considered in further refining this device. There may be greater
      latitude in the selection of air bag material. The authors believe their
      technique is applicable to the assessment of many air bag or passenger variables.

PMID- 8259281
TI  - Progressive Schnyder's corneal dystrophy.
AB  - BACKGROUND: Schnyder's crystalline dystrophy is a central anterior bilateral
      corneal dystrophy characterized by the deposition of crystals composed of
      cholesterol and other lipids. This condition classically is described as
      nonprogressive after childhood, but a series of recent studies following patients
      over time has challenged this teaching. PATIENTS: The authors present a family
      pedigree including a patient first reported in 1954 and followed for 25 years
      with dramatic progression of the corneal condition in a dense, discoid pattern of
      crystals. Best-corrected visual acuity decreased from 20/30 to 20/80 in both
      eyes. This patient now has three children, all with typical corneal involvement.
      RESULTS: Ocular pathologic examination performed on corneal biopsies submitted
      for light and electron microscopy demonstrated cholesterol deposition consistent
      with a diagnosis of Schnyder's. CONCLUSION: Schnyder's corneal dystrophy may
      progress significantly over time. The characterization of this condition as
      stationary may need to be reconsidered.

PMID- 8259282
TI  - Ultraviolet solid-state laser (213-nm) photorefractive keratectomy. In vitro
      study.
AB  - BACKGROUND: Replacing the gas argon fluoride (193 nm) excimer laser with a solid
      state laser source in the far-ultraviolet spectrum region would eliminate the
      hazards of a gas laser and would reduce its size, which is desirable for
      photorefractive keratectomy. The authors investigated corneal reshaping using a
      frequency-quintupled (213 nm) pulsed (10 ns) neodymium:YAG laser coupled to a
      computer-controlled optical scanning delivery system. METHODS: A 250 +/- 15
      mJ/cm2 radiant exposure was used to ablate a 5-mm optical zone in human cadaver
      eyes and rabbit eyes. The 213-nm laser pulses were delivered through and shaped
      by a computer-controlled optical scanning delivery system, producing a 0.5-mm
      spot with a quasi-Guassian energy distribution on the cornea. Corneal surface
      changes were documented by computer-assisted corneal topography. Light
      microscopy, scanning electron microscopy, and transmission electron microscopy
      were performed to examine the effects on corneal surface quality and cellular
      components. RESULTS: Corneal topographic measurements showed myopic corrections
      ranging from 2.3 to 6.1 diopters. Results of postoperative examination with the
      slit lamp and operating microscope demonstrated a smoothly ablated surface
      without corneal haze. Histologic results showed a smoothly sloping surface
      without recognizable steps. The surface quality and cellular effects were similar
      to that of previously described excimer photorefractive keratectomy. CONCLUSION:
      The authors demonstrated that an ultraviolet (213-nm) solid-state laser coupled
      to an optical scanning delivery system is capable of reshaping the corneal
      surface with smooth transition. The scanning beam delivery system may offer the
      advantage of producing spatially resolved, customized, aspheric corrections to
      optimize the quality of vision after photorefractive keratectomy.

PMID- 8259283
TI  - Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic
      and metal surfaces in vitro.
AB  - BACKGROUND: Prevention of the spread of epidemic keratoconjunctivitis (EKC) at
      eye care facilities (doctors' offices, clinics, hospitals) has been a major
      public health goal for ophthalmology for more than 50 years. The authors explored
      a potentially contributing attribute of the adenovirus serotypes that cause EKC.
      Specifically, they investigated the capacity of different clinical and laboratory
      ocular serotypes (AD8, 19, and 5) to survive for extended periods of time in a
      desiccated state. METHODS: Twenty microliters containing 2000 plaque-forming
      units of different ATCC laboratory adenoviral ocular serotypes (AD8, 19, and 5)
      and clinical isolates (AD8 Cray, AD19 Kowalski, and AD5 McEwen) were inoculated
      onto 7-mm plastic disks and 6-mm aluminum foil disks and were allowed to
      completely desiccate. At weekly intervals up to 7 weeks, eight desiccated virus
      inoculated plastic or metal disks per serotype were added to tissue culture
      medium, and the amount of recoverable virus was determined by plaque assay on
      A549 cells. RESULTS: Ocular adenoviral serotypes AD8, 19, and 5 could be
      recovered up to 49 days from plastic, and 35 to 49 days from metal. Sufficient
      virus concentrations (> 100 plaque-forming units/disk) to be clinically
      infectious were recovered up to 28 days. Differences in recovery among serotypes
      (AD19 > AD5, AD8) were demonstrated, but laboratory and clinical isolates of the
      same serotype were usually comparable. CONCLUSIONS: Ocular isolates of adenovirus
      that cause EKC are much harder than previously suspected, and the capacity to
      survive in a desiccated state may possibly play some role in office-based mini
      epidemics of EKC.

PMID- 8259284
TI  - Efficacy of a disinfectant wipe method for the removal of adenovirus 8 from
      tonometer tips.
AB  - PURPOSE: To determine the efficacy of a disinfectant wipe method in eliminating
      adenovirus 8 from both Goldmann tonometer and pneumotonometer tips, and to
      determine the efficacy of 5-minute disinfectant soaks in removing the virus from
      Goldmann tonometer tips. METHOD: Quantification of adenovirus 8 in the ocular
      secretions of six infected patients was performed. Clinically relevant inocula of
      adenovirus 8 were then prepared in a serum suspension which was used to
      contaminate Goldmann tonometer and pneumotonometer tips. Each contaminated tip
      was subjected to either a dry wipe or a wipe with one of the following: water,
      isopropyl alcohol, hydrogen peroxide, and iodophor. The tips were than
      quantitatively assayed for residual adenovirus 8. Disinfectant soaks were
      similarly assessed using contaminated Goldmann tonometer tips soaked in water,
      hydrogen peroxide, iodophor, and sodium hypochlorite. RESULTS: Adenovirus 8 was
      recovered from both types of tonometer tips after dry wipes, but no viable virus
      was recovered from tips wiped with water only or with any of the disinfectants
      tested. Adenovirus 8 also was recovered from Goldmann tonometer tips that were
      either rinsed or soaked in water; no virus was recovered from tips soaked for 5
      minutes in any of the disinfectants tested. CONCLUSION: A disinfectant wipe
      method using isopropyl alcohol, hydrogen peroxide, or iodophor is effective in
      removing adenovirus 8 from both Goldmann tonometer and pneumotonometer tips. Five
      minute disinfectant soaks also are effective for Goldmann tonometer tips.

PMID- 8259285
TI  - Accidental skin punctures during ophthalmic surgery.
AB  - PURPOSE: Accidental skin puncture carries the risk of both hepatitis B and human
      immunodeficiency virus transmission. There have been studies of the incidence of
      these skin punctures in general surgery, but no study has focused on ophthalmic
      surgery. METHOD: All incident reports of skin punctures in the Bascom Palmer Eye
      Institute operating rooms from January 1990 through November 1991 were reviewed
      retrospectively. The incidence of skin puncture also was studied propsectively
      from December 1991 through May 1992. During the prospective phase, the healthcare
      worker was asked to complete an anonymous form regarding the instrument involved,
      whether it was clean or contaminated, the persons involved, and whether the room
      lights were on or off. RESULTS: There were 37 such occurrences in 14,878
      operations (0.25%) during the retrospective study and 12 in 4246 operations
      (0.28%) in the prospective period. In only one case was the instrument
      contaminated by contact with a patient known to have positive serology for the
      human immunodeficiency virus. There were no documented seroconversions of
      healthcare personnel for either hepatitis B or human immunodeficiency virus. In
      63% of these occurrences, the penetrating instrument was known to be definitely
      contaminated with the patient's blood. Only one person was handling the
      instrument 84% of the time. CONCLUSION: The low but present danger to ophthalmic
      personnel during surgical procedures justifies precautions to decrease the
      occurrence of skin punctures.

PMID- 8259286
TI  - The management of punctal agenesis.
AB  - BACKGROUND: Agenesis of one or more lacrimal puncta is a rare cause of
      presentation to ophthalmologists. Where normal canalicular tissue lies within the
      lid, it may occasionally be successfully exteriorized to the conjunctival surface
      with relief of symptoms. The pattern of punctal agenesis, its relationship to the
      presence of underlying canalicular tissue, and its management have not been
      defined previously in a large cohort. METHODS: The authors reviewed the pattern
      of agenesis, underlying anatomic abnormalities and patient symptomatology in 57
      patients seen over a 10-year period. A management plan was devised for eyes with
      no puncta and those with a single missing punctum. RESULTS: Both puncta were
      absent in 53 eyes, and a single punctum was missing in 41 eyes. In 86% of eyes
      with absence of both puncta, no canalicular tissue was identified when the
      lacrimal sac was opened at surgery. The underlying canaliculus also was absent in
      patients with one absent punctum. Nasolacrimal duct obstruction frequently
      accounted for the onset of symptoms in patients with a single punctum. Fifty
      three (93%) of the 57 operated eyes were functionally cured at the completion of
      this report. CONCLUSION: Punctal agenesis usually is associated with the absence
      of underlying canalicular tissue. Where both puncta are absent, the authors
      recommend inspection of the internal opening of the common canaliculus at surgery
      and, if no canalicular tissue can be identified (86% in this series), insertion
      of a Lester-Jones tube. Symptomatic patients with a single punctum frequently
      require surgery to relieve nasolacrimal rather than canalicular obstruction.

PMID- 8259287
TI  - Primary adenocarcinoma of the lacrimal gland. A retrospective study.
AB  - BACKGROUND: Primary adenocarcinoma of the lacrimal gland is rare and usually
      appears in the literature as case reports. The authors retrospectively studied
      cases of primary adenocarcinoma of the lacrimal gland to determine which of the
      currently used methods was most effective in treating this tumor. METHODS: The
      authors requested cases of primary adenocarcinoma of the lacrimal gland from
      orbital surgeons and ocular pathologists worldwide. Of the cases referred, 13
      examples of primary adenocarcinoma of the lacrimal gland could be confirmed and
      studied for clinical features, management, and outcome. RESULTS: The authors have
      follow-up data on all 13 patients. Six patients died of cancer, three are alive
      with recurrence, and four are alive and disease-free. CONCLUSION: Based on the
      results of this study, the authors ascertain that primary adenocarcinoma of the
      lacrimal gland is not inevitably fatal and should be treated with exenteration
      and adjuvant radiotherapy as soon as a histologic diagnosis is established.
      Shorter duration of symptoms before treatment appears to decrease the chance of
      metastases and increase the chance of long-term survival.

PMID- 8259288
TI  - Serum antibody production to botulinum A toxin.
AB  - PURPOSE: Conflicting data have been reported regarding development of serum
      antibodies to botulinum A toxin. The purpose of this study is to determine
      conclusively whether antibody production to this toxin occurs in humans, and, if
      so, to determine its relationship, if any, to length of treatment, total
      cumulative dose, and clinical response to treatment. METHODS: Sixty-five sera
      samples from 42 adults treated with botulinum A toxin for essential
      blepharospasm, hemifacial spasm, or spasmodic torticollis were analyzed via a
      sphere-linked immunodiagnostic assay for antibody production. Results were
      plotted against length of treatment, number of injections, cumulative dose, and
      treatment effect produced. RESULTS: Twenty-four (57%) of the 42 patients produced
      antibodies in all three diagnostic groups. No significant differences were found
      between antibody producers and nonproducers with respect to age (P = 0.216),
      length of treatment (P = 0.586), number of injections (P = 0.619), or total
      cumulative dose (P = 0.286). Within the antibody-producing group, there was no
      significant correlation between amount of antibody and length of treatment (P =
      0.081), number of injections (P = 0.134), or cumulative dose (P = 0.250). The
      presence of demonstrable antibodies in serum did not affect the clinical
      responsiveness to injection. CONCLUSION: Antibody production is present in a
      majority of patients treated with botulinum A toxin. The sphere-linked
      immunodiagnostic assay is a reliable and reproducible method for detecting and
      quantifying these antibodies. When antibody production occurs, it is likely due
      to variations in individual immune responsiveness and appears to have no direct
      effect on the patient's clinical response to treatment.

PMID- 8259289
TI  - [Adenoid cystic carcinoma in the head and neck: clinical and pathologic review].
AB  - 19 patients with adenoid cystic carcinoma of the minor and major salivary glands
      were analysed clinicopathologically. Majority (8) of the tumours originated in
      the parotid gland. The palate was the most common location among the tumour of
      the minor salivary glands. The tumours were classified by their histology
      patterns into three groups: I tubular and cribriform pattern, II cribriform with
      less than 30% of solid pattern, III solid forms. A positive correlation between
      increasing grade and aggressive behavior was not observed in our study. All
      patients were treated with surgery. Eight of them received postsurgical radiation
      therapy. Recurrence of disease at the primary site occurred in 5 of 19 patients.
      Distant metastases developed in 3 patients. An adequate surgical excision of the
      tumour yields optimal local control and survival rates.

PMID- 8259290
TI  - [Parakeratosis of larynx as a base of cancerogenesis].
AB  - Keratosis, parakeratosis and hyperkeratosis of the larynx and hyperkeratotic
      papilloma with the inflammation should be treated as clinical precancerous state.
      Parakeratosis and cellular dysplasia are histological features of cancerogenesis.
      The patient with extensive verrucous keratosis of the larynx (described in the
      article) has been observed for 7 years. Eventually, the developed verrucous
      carcinoma of the larynx.

PMID- 8259291
TI  - [Wegener's granulomatosis as a clinical form of vasculitis].
AB  - A two cases Wegener's syndrome was described. The current knowledge concerning
      the role of neutrophils in pathogenesis of Wegener's syndrome is reviewed.

PMID- 8259292
TI  - [First cochlear implant in Poland].
AB  - The authors present a 30 year old patient whose hearing was profoundly impaired
      in the course of meningitis 12 years ago. They present details on the preparation
      of the patient for the surgery and indications for the implant, consecutive
      stages of the surgery and the first stage of the rehabilitation process are
      described. The results of the capability of electrical conductivity of the
      cochlear nerve as the direct effect of the cochlear implant and the first
      audiogram illustrating the hearing effect after the first 2 months of
      rehabilitation are presented as well.

PMID- 8259293
TI  - [Thermic investigations of the nystagmus induced in the Brunning's positions V-I
      in patients with unilateral, peripheral vestibular lesion].
AB  - There were examined 50 persons with unilateral peripheral lesion of vestibular
      system. Each patient was tested by method, in which inversion of nystagmus
      direction in respect of ampullopetal and ampullofugal stimulation followed cause
      of change of head's position--position Brunnings V-I--during irrigation 30
      degrees C. Results obtained during these method were compared with effects of
      caloric Hallpike test. The method described in these paper could supply to
      classic caloric test.

PMID- 8259294
TI  - [The influence of addiction and abstinence period on changes in vestibular organ
      in patients of Monar houses].
AB  - There isn't data concerning changes which occur to vestibular system as a result
      of chronic addiction. The aim of this study was to determine if the changes are
      dependent on the time of addiction or the time of abstinence. 113 persons, who
      were treated in Monar houses were divided into 3 subgroups (U 1-3) according to
      the time of addiction and into 4 subgroups (A 1-4) according to the time of
      abstinence. Symptoms, results of otoneurological examinations and answers from
      vestibular organs after provocation and after kinetic and caloric stimulations
      were taken under consideration. It was proved that there exists the relevant
      correlation between the whole number of symptoms and the dependence lasting over
      a year and it was also noticed that the greatest number of important symptoms
      occurs during the first two months of abstinence.

PMID- 8259295
TI  - [Cochlear implants: state of knowledge, prospects, indications for implantation].
AB  - The authors present the development of totally deaf patients treatment program
      using cochlear implants. Based on leading Europeans Centers qualification basis
      and selection criteria are discussed for this method of treatment both for adults
      and children. Next given are indications for extracochlear and intracochlear
      implants. Summarizing, they evaluate possible results using the above implants
      and prospects for the development of this program in our country.

PMID- 8259296
TI  - [On the etiology of systemic ozena].
AB  - The paper presents an outline of the function of the mucous membrane of the nose
      and the pharynx as well as the pathological changes in the mucous membrane of
      patients with ozena. It offers a feasible explanation why systemic ozena
      connected dysfunction (deficiency of iron, proteins and vitamins) is manifested
      mainly in the mucous membrane of the nose and pharynx. The author also discusses
      other possible etiologies of the disease regarding the systemic theory of ozena.
      An attempt has been undertaken to find out why ozena is almost absent, in the
      well-developed regions and why it commonly occurs in underdeveloped countries
      where the everyday diet is poor in iron, proteins and vitamins.

PMID- 8259297
TI  - [Selected problems of anatomy and pathophysiology of the otoliths and otolithic
      membrane].

PMID- 8259298
TI  - [Treatment of facial spasm with botulinum toxin].
AB  - Facialis spasmus (FS) is a chronic hyperkinesia primarily affecting patients in
      the 5th and 6th decades. Only muscles innervated by the facial nerve (FN) are
      involved. In the beginning there are only slight jerks, mostly in the region of
      the eyelid. In due course all facial muscles get involved. Spasms are worse when
      the patient is anxious, watching TV, working, driving and then restrict social
      activities. Because the etiology has not been known, a lot of methods of surgical
      and medical treatment were unsuccessful. Recently the cause has been clarified:
      FS is though to be caused by an irritation of this nerve by a blood vessel. The
      condition can be cured by an operation to separate the nerve and blood vessel. If
      an operation is thought to be inappropriate, treatment of FS may be with
      botulinum toxin (BT). BT is used in very small doses (nanograms), and is injected
      in the area of the muscle that is affected. This weakens the muscle and helps to
      prevent a spasm.

PMID- 8259299
TI  - [Chondrosarcoma of the maxillary sinus].

PMID- 8259300
TI  - [A large noncapsulated lipoma of the pharynx].
AB  - The authors present a case of a large, noncapsulated pharyngeal lipoma. Surgical
      extirpation followed the tracheostomy and ligature of the external carotid
      artery.

PMID- 8259301
TI  - [Premature tracheoesophageal fistula as a complication after short- term
      intubation of the patient after craniocerebral trauma].
AB  - We have described a rare case of early tracheo-esophageal fistula after short
      term intubation. 18-year old male patient was admitted to ICU after
      craniocerebral trauma. After 6 days of intubation the tracheo-esophageal fistula
      appeared. We suggest that tracheoesophageal fistula was caused by compression of
      the trachea by tracheostomies tube cuff, shock and poor general condition.

PMID- 8259302
TI  - [A case of traumatic stenosis of the pharynx].
AB  - Stenosis of the pharynx resulting from trauma is a major problem. Lateral
      pharyngotomy provides excellent exposure for this reconstruction. We present the
      case of traumatic stenosis of the pharynx and its treatment.

PMID- 8259303
TI  - [Tuberculosis of the larynx in patients treated in laryngological clinic No. 2 in
      Zabrze].
AB  - 3 cases of tuberculosis of the larynx were presented in this paper. Provisional
      diagnosis was tumor of the larynx. Further specialistic investigations e.g. MDL
      and biopsy were done and revealed proper diagnosis tuberculosis of the larynx.

PMID- 8259304
TI  - [Intracerebral hemorrhage and neuron-specific enolase in premature and full-term
      infants--a clinical study].
AB  - In a prospective study 199 risk newborn infants were examined by means of
      cerebral ultrasound scanning and after this the influence of diagnosed
      intracerebral events on the concentration of neuron-specific enolase (NSE) was
      determined. The NSE may be valid as an indicator of intracerebral damage. A
      significant relationship between increased concentration of NSE and intracerebral
      haemorrhage of type II could be found only for the NSE-1 (determination from
      cordblood or from blood of the first or second day of life). The same
      relationship results for intracranial cystic rebuildings, destructions and
      enlargements of ventricles. The diagnostic tests of NSE-1 for intracerebral
      haemorrhages don't prove with a validity of 57.4% high prognostic value. Not
      until a NSE-1-level of 16.0 micrograms/l a predictive value of the positive test
      of 100% was calculated.

PMID- 8259305
TI  - [Studies of fetal and neonatal isolated guinea pig lung on the effect of electric
      tissue resistance on the ECG].
AB  - The results of measurements of the electrical resistance of lung tissue are
      reported in order to estimate quantitatively the influence of air and blood
      filling on the conductivity. Experiments were done on isolated lung tissue of
      fetal and infantile guinea pigs. The ohmic resistance was measured by a minimised
      4-electrode technique: isolated fetal lungs empty of air, or artificially aerated
      ones on the one hand, isolated lungs of infantile animals with spontaneous
      respiration and normal lung blood flow on the other hand. The increase of the
      electrical resistance produced by aeration is reduced by at least 50% by the
      synchronously increasing blood flow in spontaneously respired lungs. These
      experiments in the described animal model offer an opportunity for a more precise
      interpretation of the electrocardiogram of human adults changing with respiratory
      phases.

PMID- 8259306
TI  - [Current problems in pediatric intensive care from the pathophysiologic
      viewpoint. I. Changes in body composition and fluid compartments in relation to
      age].
AB  - A sufficient intensive therapy for children requires an age related knowledge of
      the bodies composition and the connection between each individual part. A summary
      of the questions of body composition in relation to age and internal comparison
      size, especially in connection with the bodies surface will be given.

PMID- 8259307
TI  - [After-care of children with diseases of the kidneys and efferent urinary tract].
AB  - In the district of Bautzen two different systems of care in nephrologic patients
      had been established since 1974. After the clinical diagnostics and treatment in
      the district hospital they had been transmitted to pediatric practices for after
      treatment care. Beside it diagnostics and treatment in such patients was
      performed primarily in an outpatient department and the after-treatment care was
      done by the same pediatrician. In 78.4 percent of the children treated clinically
      an after-treatment care had been obtained, as was detected by a questionnaire.
      This must be of disadvantage. Relapses of the urinary tract infection occurred in
      more than 50 percent and after quite different intervals. In 27.6 percent of
      patients getting after-treatment care it was discontinued early. In the
      outpatient department 91.1 percent of all patients were under control regularly
      and for a sufficient time. More patients with chronic pyelonephritis had been
      recognized in the region of that outpatient department. The advantage of this
      system is given by a thorough supervision by the same physician above all.
      Without doubt the care for nephrologic patients can be carried out with high
      quality too by physicians in a private practice conscious of the importance of
      this task.

PMID- 8259308
TI  - [Reliability of ambulatory drug therapy in childhood].
AB  - The continuing increase in outpatient paediatric treatments requires parents to
      take more responsibility for the drug therapy prescribed. Randomly selected
      mothers were given questionnaires, to be filled in anonymously, about the
      administration of drugs frequently prescribed for their children. The evaluation
      of 888 questionnaires showed that only one-half of the prescribed drugs had been
      administered according to instruction: Expectorants and antitussive sedatives to
      52%, externals to 57%, rhinological agents to 36% and laryngological drugs to
      27%. With antibiotics, however, the compliance was higher. In order to improve
      compliance, the mutual relationship: doctor-mother-child-drug, should be
      reconsidered.

PMID- 8259309
TI  - [Psychological characteristics of boys with hypospadias].
AB  - In a pilot study psychological tests were carried out with 47 male children
      suffering from various kinds of hypospadias. In comparison with healthy children
      they showed strong feelings of inferiority and an increased sensibility, proved
      to be socially less adapted and more difficult to train. Children with mild forms
      of hypospadias had an effect being, psychologically seen, less striking. More
      aggravating mental problems were noted with increasingly frequent repetition of
      operations. Psychologically it has been stated that the most favourable time for
      first operation is the age of 5-6 years. Children submitted to an operation for
      the first time at the age of 2-4 years as well as children with a correction of
      hypospadias carried out at school-age only, proved to be more psychologically
      strained.

PMID- 8259310
TI  - [Treatment of recurrent neuroblastoma in childhood with whole body
      thermochemotherapy].
AB  - More than 30% of the children suffering from an advanced solid tumour disease or
      tumour recurrence cannot be cured despite intensive oncological treatment. A new
      possible therapy is the application of whole-body hyperthermia in childhood in
      combination with chemotherapy and radiation treatment. The fundamental principles
      and the method of the whole-body thermochemotherapy are briefly explained. The
      treatment of one patient with a neuroblastoma recurrence is reported as a
      clinical example for the effectiveness of whole-body thermochemotherapy in
      childhood and the course of therapy is discussed.

PMID- 8259311
TI  - Acute obstructive respiratory diseases (ARD) and bacterial complications of ARD
      (pneumonia, sinusitis) in infants and children associated with human herpesvirus
      6 infection.
AB  - The existence of catharreal respiratory symptoms (such as pharyngitis,
      tracheitis, bronchitis etc.) is established as the usual manifestation of
      "exanthema subitum" due to acute human herpesvirus-6 (HHV-6) infection. But so
      far pneumonia, purulent sinusitis, purulent otitis media and/or acute obstructive
      bronchitis (bronchiolitis) in infants and children have not been described. Here
      we report the results of observations of 2 children with
      bronchopneumonia/sinusitis maxillaris and severe bronchiolitis associated with an
      acute HHV-6 infection. Other respiratory viruses were excluded as agents causing
      the ARD.

PMID- 8259312
TI  - Pre- and perinatal infections due to human herpesvirus-6 and Epstein-Barr-virus
      with lethal outcome or severe residual encephalopathy.
AB  - The Human Herpesvirus-6 (HHV-6) infection causes exanthem subitum (in typical
      cases) and a wide range of other symptoms. So far no prenatal or perinatal
      infections have been reported. For HHV-6 the prenatal infection should be
      extremely rare, because more than 95% of adults are immune in Germany. Two own
      cases reported here document that pre- and perinatal HHV-6 infection does occur
      and can provoke dramatic clinical symptoms of illness with death or cerebral
      defects like other prenatal herpesvirus infections (HSV, VZV, CMV etc.).

PMID- 8259313
TI  - Reactivation in children of juvenile chronic arthritis and chronic iridocyclitis
      associated with human herpesvirus-6 infection.
AB  - The human herpesvirus-6 (HHV-6) causes exanthem subitum. Moreover it can provoke
      a large scale of different other clinical symptoms. The life-long persistence of
      human herpes viruses is well known (HSV 1 and 2, VZV, CMV, EBV). For the HHV-6 we
      have described here for the first time the onset/reactivation of juvenile chronic
      arthritis (jcA) and chronic iridocyclitis as chronically active and persistent
      infection in two children of school age.

PMID- 8259314
TI  - [Haemophilus influenzae meningitis in childhood].
AB  - From January 1971 until the end of 1989, 94 infants suffering from meningitis
      caused by Haemophilus influenzae were treated in the Department of Pediatrics of
      the University of Leipzig. The anamnestic data, signs and symptoms, laboratory
      findings, the courses and final results of treatment are described. 88 children
      survived; in eight of them neurological or mental sequelae were found on
      discharge. Generally, a certain stagnation regarding treatment results is
      observed over the observation period. Therefore vaccination against Haemophilus
      influenzae type B should be encouraged.

PMID- 8259315
TI  - [Mortality in childhood--a study of pediatric fatalities in the Magdeburg
      district].
AB  - In the present study the causes of the cases of infant mortality (1 to 16 years
      of age) in the Magdeburg district in the period from 1982-1989 are analysed. The
      causes of death are shown according to age, sex and diagnosis groups, using
      autopsy-documents and data from the district of Magdeburg. The order of diagnosis
      starts with accidents with 40%, followed by malignant neoplasm and congenital
      anomalies with 13% and 13.1%, respectively, and diseases of the nervous system
      and of the sense organs with 9.9%. Conclusion are drawn for the reduction of the
      infant mortality rate.

PMID- 8259316
TI  - [Dietary management of phenylketonuria patients using a personal computer].
AB  - The communication between the responsible physician and the family of the
      phenylketonuric patient requires an extended period of time in the treatment
      centre. Computer software was developed for the centre to ensure individual
      treatment of all patients according to the dietary recommendations. The program
      is additionally able to document all clinical data and to handle the
      correspondence with the family of the patient.

PMID- 8259317
TI  - [Conditions in stuttering. Results of an interdisciplinary study of 3- to 5-year
      old children. Neurologic aspects].
AB  - Results recorded from neurological surveys are reported in the context of an
      interdisciplinary study conducted on 67 children aged three to five years at the
      onset of speech fluency disorders as well as investigations on 50 children of
      identical age and sex. The two groups (DS: disruption of speech; CG: control
      group) significantly differed from each other regarding family predisposition for
      stuttering. Sub-coordination and whole-body coordination were investigated. Both
      the occurrence of disorders and as the number of vegetative symptoms recorded
      from DS children were significantly higher than comparable values obtained from
      CG probands. Electroencephalographic recordings were taken only from the DS
      group, with 25 percent of them being interpreted as pathological. The conclusion
      is drawn that this study, once more, has provided evidence for the existence of
      somatic predisposition which, however, must not be considered identical with
      cerebral damage.

PMID- 8259318
TI  - [Conditions in stuttering. Results of an interdisciplinary study of 3- to 5-year
      old children. Child psychiatric aspects].
AB  - An interdisciplinary study was conducted with 67 children aged three to five
      years at the onset of speech fluency impairment as well as with 50 controls
      identical to the above group by age and sex. Findings reported are on psychic
      conditions which were obtained by interviews with and examinations of parents and
      children as well as by watching children at play and by means of questionnaires.
      Children with disruption of speech (DS) significantly differed from children in
      the control group (CG) with regard to prevailing mood, affect, psychic stability,
      capability of concentration, sociability and timidity. These personality traits
      and behaviours deviating from normal with differing intensity, are interpreted as
      stutter-specific condition for consolidation of the disorder rather than as cause
      of the latter. Ways of intervention will depend on several aspects, including the
      specific influence of psychic components on the condition of the individual.

PMID- 8259319
TI  - [Social conditions of stuttering].
AB  - Sixty-seven stuttering and 50 non-stuttering children, all of them aged between
      three and five years, were investigated regarding their social conditions in an
      interdisciplinary study. Numerous studies so far conducted into family
      circumstances of stuttering children and adolescents have supported diverse
      conclusions regarding the parent-child relationship, personality traits of
      parents as well as their style of child raising and social status. Most of the
      resulting publications have concentrated on children from whom stuttering
      symptoms had been recordable for several years, so that it was not safely
      verifiable whether the parental behaviour described had been one of the causal
      factors for stuttering of children or a belated response to that stuttering. The
      author's own investigations showed significant differences with regard to
      presence in a day nursery in the child's first year, space conditions at home,
      attention given to the child, physical exercise, occupational satisfaction of
      mothers and self-appraising qualities of fathers. These differences, on balance,
      are interpreted to the effect that in the individual case stuttering may be
      affected by psychosocial conditions and would then call for therapeutic action,
      although it appears to be obvious that there are no stutter-specific social
      factors. These results are likely to confirm experience obtained from work with
      stuttering individuals by numerous medical doctors, teachers in lalopathology and
      psychologists who found that in general manifestations of stuttering may be
      caused and affected by a number of factors, both endogenic and exogenic.

PMID- 8259320
TI  - [Early infantile autism and excessive aerophagy with symptomatic megacolon and
      ileus in a case of Ehlers-Danlos syndrome].
AB  - A case of Ehlers-Danlos syndrome is reported, which was associated with mental
      retardation and early infantile autism. The patient died at the age of 19 by
      ectasy of the stomach as the result of extreme aerophagy causing a megacolon and
      by compression so finally resulting in a mechanical ileus. Investigation of the
      cerebellum revealed a significant rarefication and diminuation of the Purkinje
      cells as well as the cells of the stratum granulare in the lobuli VI and VII,
      obviously due to a genetically determined malformation.

PMID- 8259321
TI  - [Unilateral anophthalmia in association with learning handicap and affective
      disorders--contribution to Lenz syndrome].
AB  - The case of an 18-year-old debile boy with leftside anophthalmia, premature
      craniosynostosis and dysmorphias characteristic for LENZ-syndrome as well as
      episodic affective disorders is reported. Special emphasis is laid on the
      differential diagnosis of the dysmorphia retardation syndrome.

PMID- 8259322
TI  - [Possible modification of circulatory parameters of the upper extremity--using
      electrostimulation with the "Jogger" electrostimulator].
AB  - Circulatory disturbances of the upper extremities may be affected by blockade of
      the ganglion stellatum. This blockade is possible by electrical stimulation with
      pocket stimulators. Frequent blockades of the ganglion stellatum are possible,
      simple, free from pain and without drugs. Rheographic resurges and check up with
      skin thermographie will demonstrate the effectiveness of this method.

PMID- 8259323
TI  - Re-engineering.

PMID- 8259324
TI  - Interinstitutional agreement of individual functional independence measure (FIM)
      items measured at two sites on one sample of SCI patients.
AB  - Individual items of the Functional Independence Measure (FIM) were analyzed for
      interinstitutional agreement using a sample of 57 spinal cord injured (SCI)
      patients at discharge from an acute care rehabilitation setting (ACRS) and at
      admission to an ongoing rehabilitation setting (ORS). The two FIM ratings were
      performed within 6 days of each other. The reliability coefficient for total FIM
      scores was good: 0.83. Individual items were classified into four groups: (1)
      above average reliability coefficient, above average proportion agreement, which
      included the feeding items and items from the mobility category; (2) above
      average reliability coefficient, below average agreement, which included the
      majority of items in the selfcare category; (3) below average reliability
      coefficient, above average agreement, which included items in the sphincter
      control and communication categories; and (4) below average reliability
      coefficient, below average agreement, which included items in the social
      cognition category. Patients received significantly higher ratings on most
      selfcare items in the ACRS, and significantly higher ratings on social cognition
      items in the ORS. Implications of these results are discussed in terms of using
      individual FIM items for research purposes. Reliability coefficients were
      acceptably high for subgroups of complete and incomplete paraplegics and for
      complete quadriplegics, ranging from 0.74 to 0.87, but low for incomplete
      quadriplegics, r = 0.49. However, these sample sizes were small, ranging from 9
      to 17 patients. Data collection will continue in order to increase sample size
      and permit further analysis of these subgroups.

PMID- 8259325
TI  - Social support and health status in spinal cord injury.
AB  - In a mailed survey, 125 persons with spinal cord injury responded to questions on
      the SCI Quality of Life Index (QOLI), and the Reciprocal Social Support Scale.
      The results indicated that people with SCI who believe that they receive support
      from the community, compared to those who believed they received less support (1)
      perceived themselves to be better adjusted to their injury, and (2) had
      significantly fewer health problems (fewer spinal cysts, lower blood pressure,
      shorter recovery time from decubitus ulcers, less pain below the level of injury,
      and fewer hospital admissions). The results also showed that people who believe
      that they contribute to the community in some way, compared to those who believed
      they contributed little or nothing (1) perceived themselves to be better adjusted
      to their injury, and (2) had significantly fewer health problems (fewer urinary
      tract infections, fewer decubitus ulcers, less severe decubiti, less pain above
      the level of injury, and fewer hospital admissions). A community support score, a
      summary score of support given and received, was also related to adjustment and
      health.

PMID- 8259326
TI  - Methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with
      spinal cord injury.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) colonization has been a
      problem in the Rancho Los Amigos Medical Center (RLAMC) since 1978. This study
      reviews the latest 2 years' use of a protocol to prevent the spread of MRSA while
      allowing spinal cord injured patients to continue to participate in the
      rehabilitation program. The protocol included management in a private room,
      bathing with hexachlorophene, monitoring positive sites and clearing patients
      after 3 weeks of negative cultures. Clusters of cases were investigated by
      obtaining nasal cultures from the personnel. Sixty-seven of 584 (11%) SCI
      patients were colonized from July 1989 to July 1991. The prevalence of MRSA
      colonization was significantly greater in the pressure ulcer management service
      (PMS) 49/184 (27%) than in the rehabilitation spinal injury service (SIS) 18/400
      (5%). The body sites colonized were wounds (58/67), nares (37/67), throat
      (30/67), urine (27/67) and perineum (17/67). Oral therapy with combinations of
      sulfamethoxazole trimethoprim (SXT) or Novobiocin with rifampin together with
      topical antibiotics (nares and wound sites), used in nine patients with healing
      wounds or recent flap surgery, resulted in clearing of the colonization in all
      cases. Identification and treatment of carriers in the personnel and use of
      preadmission screening cultures for MRSA in patients with pressure ulcers
      resulted in reduced inpatient admission.

PMID- 8259327
TI  - Eradication of urinary tract infection following spinal cord injury.
AB  - A prospective study to evaluate the microbiological efficacy of antimicrobial
      treatment for urinary tract infection (UTI) was performed in 64 catheter-free
      spinal cord injured (SCI) patients who were visited monthly by a public health
      nurse who collected urine for culture and urinalysis. Patients also mailed urine
      dip slides for weekly bacterial counts. UTI was defined as a culture yielding >
      or = 100,000 colonies/ml. Treatment was given to asymptomatic patients only if
      pyuria (> or = 10 urinary leukocytes/high powered microscopic field) was present.
      Initial treatment was for 7-14 days (group 1). When it became apparent during the
      study that eradication was difficult and relapse or reinfection frequently
      occurred within a short time after cessation of antibiotic, a second treatment
      course of > or = 28 days (group 2) was given. By the end of the study, in which
      all patients were followed for a minimum of 30 days post treatment, 39/42 (93%)
      cases in group 1 and 11/13 (85%) in group 2 who had initial eradication, had
      relapsed or become reinfected. The median number of days and standard error for
      group 1 to relapse or become reinfected was 16 +/- 2.5, and for group 2 it was 27
      +/- 6. Development of drug resistance was documented when bacteria isolated prior
      to any treatment were compared with strains isolated after > or = 28 days of
      antibiotics. In this study, urine sterility was achieved in a minority of treated
      UTIs and was relatively short lived.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259328
TI  - Persistent hypercoagulation associated with heterotopic ossification in patients
      with spinal cord injury long after injury has occurred.
AB  - Three patients are presented with traumatic spinal cord injury (SCI) complicated
      by acute heterotopic ossification (HO), and concurrent deep vein thrombosis 15
      months, 18 months and 22 years after SCI, accompanied by persistent
      hypercoagulation. The diagnosis of HO preceded deep vein thrombosis in all three
      patients. All were treated with etidronate disodium and therapeutic heparin
      followed by oral anticoagulation. As these patients were not acutely injured, the
      questions arose as to what predisposed them to deep vein thrombosis and when was
      the appropriate time to discontinue anticoagulation. Over a course of 3 years
      following deep vein thrombosis, these patients were monitored for evidence of
      hypercoagulation by D-dimer assay, plasma fibrinogen estimation, and rate of
      whole blood clotting by Sonoclot coagulation analyzer. The activity of acute HO
      was assessed by three-phase bone scan. A steady state of hypercoagulation,
      reflected by an increase in all three parameters, ran parallel to the extent of
      acute HO for the entire observation period. Moreover, hypercoagulation was
      persistently greater during increased acute HO activity even when the warfarin
      induced prothrombin time ratio was 1.2-1.5. In addition, as acute heterotopic
      ossification activity decreased, the test values returned to near normal during
      warfarin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259329
TI  - Intravenous disodium etidronate therapy in spinal cord injury patients with
      heterotopic ossification.
AB  - The goal of the present study was to use intravenous etidronate in the acute
      phase of heterotopic ossification (HO) in an attempt to achieve a high initial
      drug concentration at the site of the active ectopic ossification. The study
      included 27 consecutive patients with an acute onset of HO after spinal cord
      injury (SCI). The three-phase bone scan was used to confirm clinical diagnosis of
      HO. Disodium etidronate (Didronel) 300 mg was administered intravenously daily
      for 3 to 5 days. In 20 patients there was a rapid (1-2 days) decrease of soft
      tissue swelling (p < 0.01) with no side effects associated with the intravenous
      administration. In seven patients there was minimal or no improvement of edema
      after intravenous etidronate. In these patients deep vein thrombosis was found in
      the affected limbs. The effect of high dose etidronate on HO was determined in
      the group of 13 patients with positive clinical and scintigraphic finding of an
      acute HO, but negative radiographic studies. After intravenous administration of
      etidronate for 3 days (300 mg/day) the drug was continued orally with 20
      mg/kg/day for 6 months. A placebo was not used in this study. In eight patients
      there was no radiographic evidence of HO after therapy while two patients had
      minimal ossifications. In three patients therapy was interrupted and all
      developed HO in 1-2 months.

PMID- 8259330
TI  - MRI evaluation of fusion mass incorporation after anterior cervical bony fusions:
      preliminary findings.
AB  - While Modic has described certain MRI changes in bone grafts in patients after
      anterior cervical discectomy and fusion (ACF), no study has evaluated specific
      MRI signal changes in the fusion mass prospectively and longitudinally. The goal
      of the present study was to prospectively evaluate MRI changes in ACF grafts in a
      longitudinal fashion. Twenty-seven MRIs were included in the evaluation of seven
      postoperative patients. MRIs were obtained in a 1.5 tesla GE imager immediately
      postoperatively, and at 1, 3, and 6 months in most patients. All patients
      received at least three sequential MRIs. Two patients had greater than one level
      fused. T1 and T2 images were evaluated in all patients at each available
      interval. GRASS images were not found to be helpful secondary to a prohibitive
      amount of noise. For single level fusion masses, T1 images showed a very intense
      homogeneous graft signal in the immediate postoperative period which decreased
      slightly at 1 month. At 3 months the signal intensity of the graft was similar to
      the 1 month image, but was slightly less homogeneous. At 6 months, the T1 signal
      had greatly decreased in much of the graft. Immediate postoperative specimens
      showed heterogeneously high signal on T2 images which increased at 1 month in the
      whole graft, and then seemed to increase at the endplates while decreasing in the
      graft at 3 months. At 6 months the graft was becoming difficult to delineate on
      T2 images in many specimens. The two and three level fusions had a more
      heterogeneous image progression without clear evidence of solid fusion at 6
      months.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259331
TI  - Intracavernous papaverine for impotence in spinal cord injured patients.
AB  - The majority of the spinal cord injury patients in our centre are young healthy
      males aged between 20 and 40 years. Loss of erection and inability to have coitus
      and father children have been responsible for inadequate sociosexual
      rehabilitation. In 1985, under urologist supervision, intracavernosal papaverine
      injection treatment was started in 101 volunteers, 65 paraplegics and 36
      tetraplegics. Satisfactory erection sufficient for coital penetration was
      possible in 98 patients. Three had prolonged erection lasting beyond 4 hours.
      Only one required irrigation of the corpus with saline to achieve detumscence.
      One patient developed cavernosal fibrosis necessitating discontinuing the
      injection. Administration was under medical supervision so that possible
      complications of priapism/systemic effects could be promptly managed.

PMID- 8259332
TI  - Spinal dural arteriovenous fistula adjacent to a spinal neurofibroma--a
      misleading coexistence. Case report.
AB  - The authors report the case of a patient harbouring a spinal dural arteriovenous
      fistula adjacent to an intradural neurofibroma. Only the latter could be
      demonstrated by the diagnostic modalities employed. Such a coexistence proved
      misleading and two interventions were needed to cure both lesions. Only one
      report has appeared in the literature dealing with such a condition. The
      possibility of such a coexistence is stressed and mechanisms are discussed.

PMID- 8259333
TI  - Amarjit Singh Chahal, medallist of the International Society of Paraplegia 1993.

PMID- 8259334
TI  - Restructured organizations: traversing hills and valleys.

PMID- 8259335
TI  - Schools as centers for collaborative services for families: a vision for change.

PMID- 8259336
TI  - Assuming responsibility for one's health: an analysis of a key assumption in
      Nursing's Agenda for Health Care Reform.
AB  - Nursing's proposal for health care reform includes an expanded role for the
      consumer of health care and an emphasis on personal responsibility for health.
      This shift in the philosophic underpinnings of the health care delivery system is
      a significant change from our current system. The impact and importance of this
      shift should not be underestimated. This article has begun an analysis of this
      shift by addressing three questions--why include these responsibility tenets now,
      what does personal responsibility in the context of health mean, and what are the
      consequences of including personal responsibility in a health care reform
      package? Nursing's Agenda for Health Care Reform is an important step forward in
      suggesting changes to our present health care delivery system. It broadens the
      scope of reform to include the consumer of health care as a major component of
      this reform. But the profession has to be clear on what the role of the
      individual is. While the individual is key to any successful change, nursing must
      be ever vigilant that the reform proposal is not used to justify unintended and
      harmful consequences.

PMID- 8259337
TI  - Removing the shackles: a feminist critique of noncompliance.

PMID- 8259338
TI  - Ethics and transcultural nursing care.

PMID- 8259339
TI  - The cultural bridge model.

PMID- 8259340
TI  - A different reflection.

PMID- 8259341
TI  - Comparison of the pathologic features and DNA ploidy value of prostate cancers
      detectable by sonography and by palpation.
AB  - Ultrasonography of the prostate detects some cancers that are not palpable, but
      the pathologic features of such cancers have not been well described. Since
      screening trials consistently find sonography more sensitive (though less
      specific) than digital rectal examination, nonpalpable cancers that are visible
      as hypoechoic lesions on ultrasound have been postulated to be early cancers of
      limited malignant potential and may not require aggressive treatment. To test
      this hypothesis, we determined the pathologic features and DNA ploidy value of
      prostate cancers in 63 radical prostatectomy specimens taken from patients with
      clinical stage T1 (n = 28) and T2 (n = 35) prostate cancer. In 40 patients (63%),
      the cancer appeared hypoechoic on ultrasound. The median volume of these cancers
      was 4.19 cm3 (range 0.45-19.22); 80% exhibited extra-capsular extension (ECE);
      30% had seminal vesicle invasion (SVI); and 95% were nondiploid by nuclear image
      analysis (CAS 200 system). In patients with isoechoic cancer, tumor volume was
      significantly less (median 0.38 cm3) and ECE and SVI occurred less frequently
      (13% and 0%, respectively). Only seven (30%) had nondiploid tumors. In 35
      patients, the tumor was palpable, and the pathologic features and DNA ploidy
      values (94% nondiploid) of these cancers were similar to those of the tumors that
      were visible on ultrasound. In seven patients, the cancer was visible by
      ultrasound but not palpable by digital rectal examination. Median tumor volume
      was 1.72 cm3 (range 0.45-18.98); four patients (57%) had ECE; one (14%) had SVI,
      and six (86%) had nondiploid cancers. We conclude that most cancers that appear
      hypoechoic on ultrasound are clinically important and exhibit aggressive
      pathologic features. Palpable cancers and sonographically visible cancers are
      similar and should be staged and treated similarly.

PMID- 8259342
TI  - Use of percutaneous transperineal 198Au seeds to treat recurrent prostate
      adenocarcinoma after failure of definitive radiotherapy.
AB  - Patients who fail external radiation therapy for prostatic cancer pose a
      therapeutic challenge. No further external radiation treatment can be delivered
      safely to the local lesion, although some patients are candidates for salvage
      surgery. In this study, 31 patients who failed prior external beam radiotherapy
      received percutaneous transperineal placement of gold seeds (198Au). Initial
      prostate volume was 17.7 cc and decreased to 10 cc 24 months after 198Au
      implantation. Of 15 patients biopsied at 12 months after treatment, 4 (27%) were
      positive, 6 (40%) were negative, and 5 (33%) showed prostate cancer with
      radiation changes. Two of three patients have died of prostate cancer, with an
      overall 5-year estimated survival of 67%. Interstitial brachytherapy was found to
      be an additional well-tolerated treatment modality in this group of 31 patients.

PMID- 8259343
TI  - Multivariate analysis of plasma hormones in patients with metastatic prostate
      cancer receiving combined LHRH-analog and antiandrogen therapy.
AB  - The following hormones, the plasma protein SHBG, and the tumor markers prostatic
      acid phosphatase (PAP) and prostate-specific antigen (PSA) were assayed at 18
      time-points over 1 month during a double-blind randomized study in 36 stage D2
      cancer patients receiving either "buserelin+placebo" or "buserelin+nilutamide
      (Anandron)": LH, FSH, estradiol, testosterone, dihydrotestosterone,
      androstenedione, 5-androstene-3,17 beta-diol, dehydroepiandrosterone and its
      sulfate, cortisol, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha
      hydroxypregnenolone, and 3 alpha-androstanediol glucuronide. Multivariate
      analysis of the treatment values (over 10,000 assays) by two complementary
      methods, correspondence factorial analysis (CFA) and the minimum spanning tree
      (MST) method, identified those variables within the pathways of androgen
      metabolism that were correlated over time and, in a comparison of the two
      treatment groups, identified the enzyme targets of nilutamide action in humans.
      Whereas nilutamide tended to decrease androstenedione slightly, it affected no
      other variables including cortisol, except for pregnenolone, 17 alpha-OH
      pregnenolone, and 17 alpha-OH-progesterone, which were increased. These increases
      are indicative of weak inhibition of C17,20 lyase by nilutamide, but, according
      to the multivariate analysis, are insufficient to account for the more marked and
      rapid fall in PAP and PSA noted on addition of nilutamide to buserelin that must
      therefore be explained by another mechanism such as androgen receptor blockade by
      nilutamide.

PMID- 8259344
TI  - Characterization of a soluble LHRH-degrading activity in the rat ventral
      prostate.
AB  - Recent evidence supports the hypothesis of a direct action of LHRH at the level
      of the prostate. Since peptidases able to degrade the hormone are present in
      several LHRH target structures, it was deemed of interest to investigate whether
      the prostate of adult normal male rats might possess LHRH degrading activities
      (LHRH-DA). Through the use of RP-HPLC, it has been observed that LHRH-DA is
      present in the soluble fraction of the rat ventral prostate homogenate, and is
      able to hydrolyze synthetic LHRH and to generate fragments 1-3 and 1-5 of the
      decapeptide. The degradation of [pGlu-3H]LHRH is inhibited by LHRH itself, and
      affected by several LHRH agonists and antagonists with different kinetics and
      potencies. TRH, the enkephalin analog [D-Ala2-D-Leu5]enkephalin and rat prolactin
      do not inhibit the degradation of [pGlu-3H]LHRH by the soluble fraction of
      prostate homogenate; on the contrary, this is inhibited by graded doses of
      somatostatin. The prostatic LHRH-DA is also inhibited, in a dose dependent
      manner, by bacitracin, serine protease inhibitors (diisopropylfluorophosphate and
      phenylmethansulfonylfluoride), the metal chelating agent EDTA, HgCl2, and
      dithiothreitol. No inhibitory effect on [pGlu-3H]LHRH hydrolysis was observed
      after incubation of the prostatic extract in the presence of captopril. The
      prostatic LHRH-DA seems to be different from that present in other tissues of the
      rat (e.g., hypothalamus, pituitary, gonads), and to be decreased by castration
      performed 3 weeks before. These results suggest that (1) an LHRH-DA is found in
      the soluble fraction of rat prostate homogenate; (2) this enzymatic activity
      exhibits the characteristics of a metallo- and thiol-dependent neutral
      endopeptidase; (3) it appears to be different from similar hydrolytic activities
      found in other tissues; and (4) it is influenced by the hormonal milieu, since
      castration causes a significant decrease of its activity.

PMID- 8259345
TI  - Effects of cis-4-hydroxy-L-proline on the androgen-induced growth of the lateral
      prostate of the prepubertally castrated guinea pig.
AB  - The present study examined the effects of cis-4-hydroxy-L-proline (CHP), a
      proline analog, on the androgen-induced growth of the lateral prostate of
      prepubertally castrated guinea pigs. Prepubertal male guinea pigs were castrated
      at the age of 3 weeks and allowed to recover completely before subjection to an
      experimental regime to alter the stromal collagen synthesis by CHP. The animals
      were kept on a special proline-deficient diet (PDD) for a week before the
      subcutaneous injection of CHP (200 mg/kg/day) for 3 days, followed by a combined
      injection of CHP and dihydrotestosterone (DHT) (10 mg/kg/day) for 10 days.
      Control animals were injected with saline and DHT only. At the end of the
      experiment, the lateral prostate was removed and examined by 1) conventional
      transmission electron microscopy (TEM), 2) staining of proteoglycans (PGs) by
      Cuprolinic Blue (CB) using the critical electrolyte concentration (CEC) method,
      3) carbohydrate and lectin histochemistry, and 4) electron microscopy (EM) lectin
      gold labelling. The results showed that the wet weight of prostate from CHP
      treated animals was significantly lower than the control and recovery groups. The
      epithelium was low columnar with an obvious increase in intercellular spaces and
      number of basal cells. The glandular cells showed little secretory activity with
      a decrease in number of granular endoplasmic reticulum (GER) profiles, secretory
      granules, and a small Golgi apparatus. The stroma was composed of stromal cells
      separated by large intercellular spaces with very sparse collagen fibrils, and a
      decrease in stromal PGs especially those PGs normally associated with collagen
      fibrils. CHP treatment also caused perturbation and disorganization in the
      epithelial basement membrane. The results suggested that stromal collagen is
      essential in mediating the response of glandular cells to DHT stimulation.
      Defective stromal collagens hamper the responsiveness of prostatic gland to
      androgen.

PMID- 8259346
TI  - [How do mothers experience and cope with sexual abuse of their daughters?].
AB  - Previous studies especially research done by systemic family-therapists stressed
      the importance of the role of the mother in sexual abuse of children by male
      family members. The literature on the reactions of mothers and their coping with
      the situation after disclosure will be reviewed. Our own qualitative studies on
      the reactions of mothers showed, that the disclosure is a multiple crisis for the
      mother: (a) A crisis and/or breakdown of the hitherto existing concepts of
      partnership; (b) the mothering-competence is called in question; (c) breakdown of
      the previous self assertion and self concept as a woman; (d) psychosocial crisis
      of bereavement and/or conflicts and changes in all relationships (isolation,
      loneliness); (e) material and economical crisis. Different case examples will be
      given in order to illustrate the findings. Finally the importance of these
      findings for consulting and therapeutic work with mothers will be discussed.

PMID- 8259347
TI  - ["I have never said anything"--a retrospective biographical study of sexual abuse
      of boys].
AB  - A summation will be provided concerning the extent of the sexual abuse of boys
      and the consequences arising there from. A qualitative study involving 10
      interviews with men who were abused will be introduced. Previous studies have
      tended to be one sided concerning the emphasis placed on the development from
      having been abused, to becoming an abuser. Through our research we have
      discovered two additional types of coping mechanisms outside the established
      criteria. These being, complete avoidance of known masculine behaviour and, the
      emulating of known masculine behaviour thus creating a facade to disguise
      insecurities. In conclusion, specific gender characteristics concerning the
      coping patterns of abused boys will be discussed.

PMID- 8259348
TI  - [Development and evaluation of a program for preventing sexual abuse in the
      preschool age].
AB  - The present study reports on the development and evaluation of an intervention
      program to prevent sexual abuse in the preschool age. The main aim of the program
      is to increase the social competencies of preschool children. Starting from
      critiques at existing prevention programs an intervention adapted at the
      cognitive abilities of preschool children was developed. The central themes of
      the program are the abilities to deal with feelings, touches, secrets, saying no,
      and getting support. The program effects were tested by an experimental study.
      Subjects were 80 preschool children aged 4 to 6 years. Forty children
      participated at the program while the other children served as control group. The
      results show clear increases of knowledge on all program dimensions which were
      stable over an interval of at least two months. The implications of the results
      for the use of prevention programs for sexual abuse in the preschool age are
      evaluated and discussed.

PMID- 8259349
TI  - [Qualitative research approaches in practical use in child and adolescent
      psychiatry].
AB  - Experimental study designs and quantitative analysis are dominating the
      methodology of child psychiatric research. Sometimes the "box of tools"
      consisting of standardized software packages for statistical analysis seems to
      lead to a regrettable uniformity in research strategies. Elaborated sociological
      research concepts in the tradition of Max Weber and the "Chicago school" could
      close the scientific gap between quantitative studies on large samples and simple
      case-reports. They are excellent instruments for generating hypothesis on
      relatively rare clinical problems or in new fields of child psychiatric research.
      Based on a review of the literature potential applications of qualitative
      methodology in child psychiatry will be discussed.

PMID- 8259350
TI  - [Role and responsibilities of psychosocial personnel in the pediatric clinic:
      (II). Psychosocial management means experimenting].
AB  - To prevent possible fragmentation of professional networks, as described in part
      I, the psychosocial co-worker should be flexible to negotiate his or her role.
      Therefore main areas of beneficial contributions are described: Ameliorating the
      context of hospital care (including child-adequate alterations of the physical
      environment; improving cooperation among the staff; staff-counseling); supportive
      psychotherapy; educative approaches and programmes; enhancing patient and family
      members to communicate illness-related issues; and discussing easily omitted
      aspects of illness among self-help-groups. This description of heterogeneous
      tasks should remind the (whole group of) psychosocial co-worker(s) that casework
      is not the only topic, they are good and necessary for, even though these other
      areas are not very well-established, yet.

PMID- 8259351
TI  - [Proton therapy, the future of radiotherapy?].

PMID- 8259352
TI  - [Peri-ungual capillaroscopy. Value in the diagnosis of systemic diseases].
AB  - The diagnostic value of nailfold capillaroscopy was assessed through blind
      analysis of a continuous series of 354 examinations. Major and minor dystrophies
      and capillary bed abnormalities are the best criteria, especially in patients
      presenting with vascular disorders of the upper extremities. A systemic disease
      (specificity: 82.7 percent; negative predictive value (NPV): 90.2 percent) and
      specifically a systemic scleroderma (sensitivity: 97.1 percent and NPV: 99.4
      percent) is improbable in case of normal capillaroscopy. First component analysis
      distinguished patients with definite systemic disease from normal subjects. Its
      value is dubious in other connective tissue diseases systemic lupus
      erythematosus, rheumatoid arthritis, Sjogren's disease, etc.).

PMID- 8259353
TI  - [Enteral nutrition in patients with chronic obstructive bronchopathy treated by
      artificial ventilation. Effect of conventional feeding on anthropometric and
      biochemical parameters].
AB  - The influence of conventional gastric tube feeding on anthropometric and
      biochemical parameters was studied prospectively during 12 months in 14 patients
      with chronic obstructive lung disease put on mechanical ventilation for
      respiratory failure. The anthropometric parameters were: body weight, tricipital
      skin fold, brachial and brachial muscle circumferences. The biochemical
      parameters included albumin, transferrin, retinol binding protein, transthyretin,
      acid alpha-1-glycoprotein, C-reactive protein, fibronectin and amino acids in
      blood, and 3-methylhistidine in urine. Measurements were performed on inclusion,
      then every 3 days until D15. After 15 days of a nutrition bringing 28.8 +/- 8.9
      calories/kg/day and 13.9 +/- 2.2 grams of nitrogen per day, no improvement in
      anthropometric parameters was observed. On D0, comparisons with healthy controls
      showed that visceral serum proteins levels were significantly lower and
      inflammatory proteins levels significantly higher (P < 0.05); the levels of
      protein metabolism markers were higher, but not significantly, and those of the
      principal glucose-forming amino acids were significantly lower (P < 0.01). On
      D15, comparisons with the initial values showed that the values of retinol
      binding protein and transthyretin were increased (P < 0.05 and 0.01
      respectively), whereas the values of the other visceral proteins were little
      modified; yet their concentrations remained significantly lower than those found
      in controls, except for the retinol binding protein. Inflammatory proteins levels
      were high, with a significant (P = 0.05) difference for the acid alpha-1
      glycoprotein, and the patients remained in slight catabolism while their nitrogen
      balance was positive. These results should encourage to carry out studies on the
      qualitative composition of artificial nutrition in order to optimize its
      effectiveness in the treatment of these patients.

PMID- 8259354
TI  - [Prosthetic duplication of the ascending aorta].
AB  - A simple implantation technique for multiple bypass of the ascending aorta with
      cervico-encephalic and infradiaphragmatic targets is reported. A conduit made by
      termino-terminal suture of two bifurcated grafts is anastomosed latero-laterally
      to the ascending aorta. The procedure is easy to perform and provides a suitable
      trajectory to the grafts.

PMID- 8259356
TI  - [Plant thorn synovitis caused by Pyracantha coccinea (burning bush)].

PMID- 8259355
TI  - [Diagnosis of diffuse encephalopathies in adults with HIV infection. 2].
AB  - A variety of the central nervous system lesions may cause a diffuse
      encephalopathy in AIDS patients. Apart from viral encephalitides already
      described in part one, metabolic encephalopathies are a classical cause of
      diffuse brain dysfunction and are frequent at the terminal stage of the disease.
      Atypical forms of some infectious, vascular or tumoural processes which usually
      determine focal lesions, may cause diffuse encephalopathies. These forms are not
      exceptional in AIDS. The association in the same patient of lesions due to
      different agents is the rule. Whereas most of the neurological complications of
      AIDS occur late in the course of the disease, symptomatic, usually transient
      encephalopathies have been described in the early stages of HIV infection in rare
      cases. The authors conclude by proposing a management plan, since therapeutic
      advances have raised some hopes of improvement and even regression of some of
      these disorders in a few cases, so that physicians do not systematically give up
      when an AIDS patient presents with a diffuse encephalopathy.

PMID- 8259357
TI  - [Mixte community-acquired Legionella pneumophila and Staphylococcus aureus
      pneumonia].

PMID- 8259358
TI  - [Interstitial respiratory syncytial virus pneumonia in hairy-cell leukemia].

PMID- 8259359
TI  - [Systematic pulmonary radiographies in hospital personnel].

PMID- 8259360
TI  - [Algodystrophy and osteomalacia].

PMID- 8259361
TI  - [Isolated atrial fibrillation. Risk of embolism and its prevention].

PMID- 8259362
TI  - [Recommendations for BCG vaccination in Germany. German Central Committee for
      Control of Tuberculosis and the current Vaccination Commission of the Federal
      Health Office].

PMID- 8259363
TI  - [Abnormalities of the lung].
AB  - Inborn abnormalities of the lung are rarely seen by clinicians. This paper
      reports about the cases obeyed within a ten-years-space in a lung-clinic.
      Symptoms, diagnostic procedure, and treatment are described.

PMID- 8259364
TI  - [Three cases of a fulminant course of idiopathic pulmonary fibrosis (Hamman-Rich
      syndrome)].
AB  - The Hamman-Rich syndrome is defined as an acute pulmonary disease of unclear
      aetiology that takes a rapid and prognostically unfavourable, usually fatal
      course. We report on three patients admitted to the intensive-care ward during a
      period of 6 months in a state of mandatory artificial respiration, each patient
      dying within 3 weeks after admission. Basing on clinical and histological
      criteria these patients were diagnosed as suffering from Hamman-Rich syndrome. At
      the time of the clinically identifiable onset of the disease all the patients had
      fever (> 39 X), leucocytosis (> 20 x 10(3)/microliters) and dyspnoea. These signs
      and symptoms were at first, in conjunction with the radiological identification
      of diffuse pulmonary infiltrations, misdiagnosed as pneumonia. The patients had
      to be artificially respirated after a short time because of the foundroyant
      course of the disease. Despite optimised respiratory parameters it was already
      initially apparent that there was a severe disturbance of the gas exchange
      function (paO2/FiO2 < 150) and high respiratory pressures (> 40 mmHg).
      Polymorphonuclear neutrophilics dominated in the bronchoalveolar lavage. Lung
      biopsy showed marked fibrosing that was a decisive factor in diagnosing. An
      infectious agent as triggering cause of the disease could not be identified in
      any of the patients. Treatment was effected with antibiotics, steroids and
      cyclophosphamide. The patients died after 14, 17 and 21 days, respectively, from
      intractable respiratory insufficiency with increasing loss of compliance of the
      lungs (compliance of lungs and thorax < 20 ml/mmHg).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8259365
TI  - [Whole body plethysmography for determining intrathoracic gas volume].
AB  - For early diagnosis of lung diseases the plethysmographic measurement of IGV is
      important. The influences of gases in the abdomen as the influences of pressure
      swings between mouth and alveolar space were several times investigated and did
      not show clinical relevance. The position of the mouthpiece in relation to the
      measured person should be taken carefully into consideration. We compared for the
      measurement of the occlusion-angel, which allows the calculation of the IGV, the
      panting- with the breathing going-on method. On 42 persons there were no
      significant differences between the results (o different laboratories: painting-
      breathing going-on = 2.8 resp. -0.6%). We prepare the breathing going-on method
      because it seems better that the person does not change his breathing level what
      could happen during the otherwise necessary instruction of the person.

PMID- 8259366
TI  - [Analysis of the current status of asthma education for children and adolescents
      in German-speaking countries].
AB  - Systematic training of children and adolescents to cope with asthma has been
      practised in Germany for long years parallel to the development of training for
      adult asthmatics. An analysis conducted in mid-1992 revealed a considerable gap
      between the actual need for such training and the available training facilities.
      The analysis covered asthma training both for outpatients and inpatients
      including those referred to rehabilitation hospitals. The analysis revealed that
      there have been some achievements in the topics that were analysed (general
      framework of conditions for training, target groups of patients, agreement on the
      direction in which to proceed with regard to scope and aims, follow-up and
      aftercare, interdisciplinary exchange of ideas and actions, financing and
      government-piloted sponsorship by the compulsory health insurance bodies,
      qualification of the asthma pupils and evaluation), whereas in many cases these
      achievements are in the nature of a pilot study or of a matured model without
      meeting as yet the essential conditions for a full-range and adequate asthma
      training offer that can be realised in a sufficiently large area. However, a
      general consensus has been reached recently on medical contents of the training,
      on problems of methods and didactic approach and also on standards of evaluation.
      The paper expressing this general consensus was passed on the occasion of the 3rd
      Annual General Meeting of the Work Team for Asthma Training in Childhood and
      Adolescence. This means that the essential prerequisites for expanding the
      training programme from a local to a large-area programme have now been created.

PMID- 8259367
TI  - [Epidemiology of sarcoidosis].
AB  - The Sarcoidosis is a world-wide phenomenon. The history of its epidemiological
      investigation is very instructive. The expectancy of noted sarcoidosis-researches
      that epidemiologic studies might also help to find out the cause of sarcoidosis
      failed. The available epidemiologic data are still confuse--the probable reasons
      for that has been explained. Socio-economic parameters--hitherto neglected--find
      increasingly consideration. The incidence is the only parameter which is suitable
      for reflecting the epidemiologic situation exactly. The principal problem of a
      reliable epidemiological research in sarcoidosis is world-wide the mode of
      ascertainment of the diseased persons. There is no evidence for an increase of
      the disease in the last 30 years.

PMID- 8259369
TI  - Index of the protein sequences added in 1991 to the Protein Sequence Database of
      the International Association of Protein Sequence Databanks (PIR-International).

PMID- 8259368
TI  - [Extensive pulmonary tumor embolisms of anaplastic thyroid gland carcinoma as a
      rare cause of hemorrhagic pleural effusion in an 88-year-old patient].
AB  - An 88 year old woman without substantial previous illness was admitted to
      hospital because of a rapidly developing dyspnea and thoracic pains. X-Ray, CT
      scan and ultra sound showed a subdivided pleural effusion of the left side. After
      a short time a pulmonary infiltrate as well as a contralateral pleural effusion
      developed. Neither tumor cells nor mycobacteria could be detected in repeated
      pleural punctions. The general condition of the patient was deteriorating
      continuously while an antibiotic therapy given in the meantime only led to a
      temporary recovery. Three weeks later the patient died under the picture of a
      cardio-respiratory failure. At autopsy the lungs showed parenchymal haemorrhages
      and multiple infarctions as well as pleural effusions. The above mentioned
      changes could be explained histologically by tumor embolism of small pulmonary
      arteries from an anaplastic thyroid carcinoma. The discussion gives a short
      survey about already published cases of tumor embolism in the lung. PMVC as the
      diagnostic method of choice is discussed.

PMID- 8259370
TI  - Monthly prostaglandin bibliography prepared by Sheffield University Biomedical
      Information Service.

PMID- 8259371
TI  - Prostaglandin biosynthesis in the microcirculation: regulation by endothelial and
      non-endothelial factors.

PMID- 8259372
TI  - Leukotriene B4 generation by blood polymorphonuclear leukocytes after incubation
      in urine.
AB  - To investigate the capacity of leukocytes in urine to produce leukotriene B4
      (LTB4), we evaluated calcium ionophore A23187-induced LTB4 generation by human
      blood polymorphonuclear leukocytes (PMNL) after these cells were incubated in
      urine under various conditions. LTB4 production was markedly reduced after
      incubation of PMNL in urine of high or low pH and high osmolarity. The production
      was also inhibited by a prolonged incubation period. There was a significant
      correlation (r = 0.82, p < 0.01) between LTB4 production and PMNL viability. Our
      results indicate that it is possible to evaluate the LTB4 production capacity of
      urinary PMNL by determining PMNL viability only. Furthermore acidification of
      urine hamper the LTB4 generation which might be unfavorable in vivo.

PMID- 8259373
TI  - Bimodal regulation of adenylate cyclase by prostaglandin E2 receptors in porcine
      ciliary epithelium.
AB  - Prostaglandin E2 (PGE2) binding revealed that porcine ciliary epithelial
      membranes possess two subclasses of binding sites or receptors. Ciliary
      nonpigmented epithelial (NPE) membranes have two binding sites (Kd,1 = 35 x 10(
      9) M, Bmax,1 = 485 x 10(-12) mol/mg protein; Kd,2 = 0.723 x 10(-6) M, Bmax,2 =
      1473 x 10(-12) mol/mg protein), while pigmented epithelial (PE) membranes have
      one binding site (Kd = 82 x 10(-9) M, Bmax = 377 x 10(-12) mol/mg protein). The
      three sites of NPE/PE membranes were found to show the highest affinity for PGE2
      by competitive binding assay; affinity for PGF2 alpha and PGD2 was several orders
      of magnitude less. PGE2 binding to the higher affinity site of NPE membranes
      induced inhibition of adenylate cyclase activity. Activation of the lower
      affinity site resulted in activation of the cyclase activity. PGE2 binding to PE
      membranes caused inhibition of adenylate cyclase activity. There is evidence that
      cyclic adenosine monophosphate (cAMP) affects transport of ions and water in the
      ciliary epithelium, hence modulates aqueous humor inflow. The present results,
      therefore suggest that aqueous humor production by the ciliary NPE cells may be
      influenced by changes in the concentration of PGE2 which binds to the receptor
      subtypes having opposing effects on adenylate cyclase and regulates intracellular
      cAMP level.

PMID- 8259374
TI  - The effect of ascorbate on essential fatty acid composition in B16 melanoma
      cells.
AB  - Ascorbate has been shown to be involved in essential fatty acid (EFA) metabolism,
      resulting in the suggestion that the effect of ascorbate on cell growth may be
      mediated through an influence on the metabolism of these FAs. This study examined
      the effect of ascorbate, supplemented over the nutritional concentration range of
      0-100 micrograms/ml, on the in vitro cell growth of non-malignant LLCMK (monkey
      kidney) cells and malignant B16 murine melanoma cells. The effect of ascorbate on
      EFA composition was also investigated, and involved the determination of the
      levels of linoleic acid (LA), gamma-linoleic acid (GLA), dihomogammalinolenic
      acid (DGLA) and arachidonic acid (AA) present in the stroma and membrane of the
      two cell types. Ascorbate had no significant inhibitory or stimulatory effect on
      the growth of either the LLCMK or B16 cells. EFA levels detected in the LLCMK
      cells were generally higher than those detected in the B16 cells. The %
      composition of the various EFAs in the stroma fractions of the two cell types
      were higher than the level of the corresponding EFAs in the membrane fractions.
      GLA levels were not detectable in the membrane fractions of the B16 cells. AA %
      composition determined in both cell types, was greater than that of any other EFA
      % composition.

PMID- 8259375
TI  - Endogenous prostaglandin E2 modulates calcium-induced differentiation in human
      skin keratinocytes.
AB  - The concentration of extracellular calcium appears critical to the initiation of
      keratinocyte differentiation. Prostaglandins (PGs) have also been implicated in
      cell differentiation. Consequently, the participation of endogenous eicosanoids
      in calcium-induced differentiation of human keratinocytes was evaluated in vitro.
      Our results demonstrate that: (1) exogenously introduced PGE2, the major
      keratinocyte-derived eicosanoid, but not prostaglandin I2 (PGI2) or its stable
      metabolite 6-keto-PGF1 alpha, enhances calcium-induced cornified envelope
      formation, an established marker of keratinocyte differentiation; (2) increasing
      extracellular calcium increased endogenous PGE2 synthesis by cultured
      keratinocytes; (3) blocking endogenous PGE2 synthesis with indomethacin
      significantly suppresses calcium-induced formation of the cornified envelope; and
      (4) adding back PGE2 to indomethacin-treated keratinocytes is able to re
      establish the control level of cornified envelope formation following stimulation
      by calcium. These data document the participation of endogenously generated PGE2
      in the modulation of calcium-induced differentiation by human keratinocytes.

PMID- 8259376
TI  - Anti-platelet and anti-thrombotic effects of OP-41483.alpha-CD, a prostacyclin
      analogue, in experimental animals.
AB  - The effects of OP-41483.alpha-CD, 5(E)-6,9-deoxa-6,9 alpha-methylene-15
      cyclopentyl-16,17,18,19,20-pentanor prostacyclin (PGI2).alpha-cyclodextrin
      clathrate, on platelet function and experimental thrombosis were studied. In
      human platelets, OP-41483 inhibited aggregation induced by adenosine diphosphate
      (ADP) or collagen, promoted disaggregation, and elevated cyclic adenosine
      monophosphate (cAMP) levels in vitro at the same order of concentrations. The
      equipotent antiaggregatory activity of OP-41483 to human platelets was observed
      in monkey platelets in vitro. Furthermore, intravenous administration of OP-41483
      to monkeys, unlike PGI2, showed the antiaggregatory effect on platelets but with
      less effect on blood pressure, suggesting that a differential sensitivity to OP
      41483 between platelet function and vascular tone exists in monkeys. In rabbits,
      OP-41483.alpha-CD attenuated platelet aggregation induced by ADP, collagen and
      platelet activating factor (PAF), decreased circulating platelet aggregates, and
      inhibited platelet adhesiveness to de-endothelialized blood vessels. These
      results suggest that the anti-thrombotic effects of OP-41483 are associated with
      its potent antiplatelet activities mainly because of the elevation of cAMP levels
      in the platelets. The potent anti-thrombotic and less hypotensive effects of this
      compound may be useful for various thrombotic disorders.

PMID- 8259377
TI  - Effect of diethylnitrosamine on prostaglandin E and lipid peroxidation levels in
      rat's liver, lung and renal tissue.
AB  - We have investigated the generation of a prooxidant state and effect on
      prostaglandin E (PGE) levels after administration of diethylnitrosamine (DENA) to
      rats. Lipid peroxides were assayed by monitoring thiobarbituric acid (TBA) a
      reactive material. PGE--like activity was assayed by using bioassay procedure.
      Our results demonstrate that increased lipid peroxide and decreased PGE levels
      were found in a dose dependent manner in DENA injected groups when compared to
      control groups. According to these findings, it is suggested that there is a
      negative correlation between carcinogenic DENA induced lipid peroxidation and PGE
      in rat's liver, lung, and renal tissue.

PMID- 8259378
TI  - Comparative study of diets enriched with evening primrose, black currant, borage
      or fungal oils on blood pressure and pressor responses in spontaneously
      hypertensive rats.
AB  - The effects of oils enriched with gamma-linolenic acid (GLA) on blood pressure
      and pressor responses were examined in spontaneously hypertensive rats (SHR).
      Rats were fed purified diets containing evening primrose (EPO), black currant
      (BCO), borage (BOR) or fungal (FGO) oils for 7 weeks. Significant reductions in
      blood pressure were obtained in SHR rats maintained on diets enriched with GLA
      oils. The antihypertensive effect was not associated with enhanced pressor
      responsiveness to norepinephrine or angiotensin II. Moreover, no differences were
      found in blood pressure responses to the calcium channel blocker, verapamil. The
      results suggest that GLA-enriched oils inhibit the development of hypertension in
      the SHR rat. The blood pressure lowering effect is not mediated by altered
      pressor responses to vasoconstrictor hormones or intracellular calcium
      mechanisms.

PMID- 8259379
TI  - Sodium loading and renal prostaglandins in old rats.
AB  - 1. Previous studies have shown that altered synthesis of prostaglandins (PGs) in
      the kidney of ageing rats contributes to impaired Na conservation during sodium
      deprivation. In the present study, we wished to assess whether the disturbance of
      prostaglandin synthesis also affects the response to sodium loading in old rats.
      2. We measured the urinary excretion of thromboxane B2 (TXB2), 6-keto PGF1 alpha
      (6KPGF1 alpha) and PGE2 in young (3-4 months) and old (20-21 months) rats after
      24, 48 and 72 h of Na loading. In a separate protocol, we measured prostanoid
      synthesis by isolated glomeruli, cortical homogenates, medullary and papillary
      slices from young and old rats in basal conditions and after 15 days of dietary
      Na loading. 3. Young and old rats excreted similarly the Na load. The urinary
      excretion (U) of TXB2 and 6KPGF1 alpha were unchanged during Na load in young
      rats. U6KPGF1 alpha, which was significantly higher in old rats and UTXB2 which
      also tended to be elevated, decreased in old rats with Na loading. Sodium loading
      was associated with a transient increase of UPGE2 in young, but not in old rats.
      4. TXB2 synthesis was increased in all portions of the kidneys of old rats.
      6KPGF1 alpha production was elevated in glomeruli and cortex and that of PGE2 in
      cortex. In medulla and papilla only TXB2 synthesis was enhanced. 5. Sodium
      loading did not significantly change prostanoid synthesis in the kidneys of young
      rats. In old rats, glomerular and cortical TXB2 decreased whereas medullary and
      papillary 6KPGF1 alpha increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259380
TI  - Expression of prostaglandin E2 receptor in hamster buccal pouch: effect of benzo
      (a) pyrene and nicotine.
AB  - Prostaglandin E2 (PGE2) plays an important role in the maintenance of oral
      mucosal integrity. In this study, we characterized PGE2 receptor binding in the
      buccal mucosa of Syrian hamster and assessed the effect of nicotine (NC) and
      benzo (a) pyrene (BP), the two major ingredients in cigarette smoke, on this
      receptor. Adult male animals were treated for 4 weeks by apical swabbing of the
      buccal pouch with corn oil (control, C), 1 mM NC, BP, or NC + BP in corn oil,
      twice a day, 5 days a week. The results obtained with the untreated group
      revealed the presence of a specific PGE2 receptor consisting of two binding sites
      (high affinity with Kd = 1.52 nM and Bmax = 37 fmol/mg protein and low affinity
      with Kd = 813 nM and Bmax = 1.29 pmol/mg protein). The treatment with NC, BP, and
      NC + BP caused a significant decrease in PGE2 receptor binding (specific binding:
      10.20 +/- 0.42, 6.84 +/- 1.32**, 6.58 +/- 0.67** and 5.88 +/- 1.03** fmol/mg
      protein; C, NC, BP, and NC+BP, respectively; Mean +/- SD, n = 5, **p < 0.01). The
      data suggest that decreased receptor binding for PGE2 in the buccal mucosa may be
      the cause for the adverse effect of cigarette smoke on the health of oral mucosa.

PMID- 8259381
TI  - Casein kinases: pleiotropic mediators of cellular regulation.
AB  - The present review on casein kinases focuses mainly on the possible metabolic
      role of CK-2, with special emphasis on its behavior in pathological tissues. From
      these data at least three ways to regulate CK-2 activity emerge: (i) CK-2
      activity changes during embryogenesis, being high at certain stages of
      development and showing basal activity values at others; (ii) CK-2 activity can
      be enhanced in vitro by treatment of tissue culture cells with various growth
      factors and serum and (iii) CK-2 activity is constitutively enhanced in rapidly
      proliferating cells. The regulated CK-2 activity changes during embryogenesis
      cannot be explained as yet. In the case of the constitutive high expression of CK
      2 in tumors, genetic changes may be responsible, e.g. through alterations of the
      regulatory genetic elements and/or regulation by specific transcription factors.
      In the case of serum induction, no genetic changes are necessarily involved; the
      observed changes may be entirely due to a signal transduction pathway where CK-2
      could be phosphorylated by another kinase(s). CK-2 cDNAs from various organisms
      have been isolated and characterized. From the deduced amino acid sequence it
      turns out that CK-2 subunits are highly conserved during evolution. The
      relationship between CK-2 alpha from humans and plants is still 73%. Similar
      relationships are reported for the beta-subunit. Chromosomal assignment of CK-2
      alpha shows two gene loci, one of which is a pseudogene. They are located on
      different chromosomes. Expression of the CK-2 subunits in Escherichia coli and
      the Baculo expression system is shown. The recombinant subunits can self-assemble
      to a functional holoenzyme in vitro. Biochemical and biophysical analysis of the
      recombinant beta-subunit suggests it to be trifunctional in association with the
      alpha-subunit affecting: (i) stability, (ii) enzyme specificity and (iii) enzyme
      activity. The question where CK-2 and its subunits are located throughout the
      cell cycle has also been addressed, mainly because of the large discrepancies
      that still exist between results obtained by different investigators. Tissue
      specific expression of CK-2 at the mRNA and at the protein level has also been
      given attention. The fact that the enzyme activity is surprisingly high in brain
      and low in heart and lung may be indicative of involvement of CK-2 in processes
      other than proliferation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8259382
TI  - The structure and specificity of endothelin receptors: their importance in
      physiology and medicine.
AB  - In addition to involvement in vascular endothelium-smooth muscle communication,
      the secretion of and receptors for, endothelins are widely distributed. Two
      cloned receptor subtypes are G-protein-coupled to several intracellular
      messengers, predominantly inositol phosphates. From a knowledge of structure
      activity relationships and peptide conformations, details of receptor
      architecture and selective agents, including nonpeptides and antagonists, have
      been discovered. From the nature of the actions of endothelins, receptor
      distributions (including CNS) and plasma levels, it is concluded that they are
      paracrine factors normally involved in long-term cellular regulation, but which
      may be important in several pathologies, many of which are stress-related.

PMID- 8259383
TI  - [The psychiatric hospital in Wart in 1908-1988].

PMID- 8259384
TI  - Intracranial vertebrobasilar system: MR angiography.
AB  - PURPOSE: To determine the reliability of magnetic resonance (MR) angiography in
      depicting normal vascular anatomy and its usefulness in detecting vascular
      disease compared with those of digital subtraction angiography (DSA). MATERIALS
      AND METHODS: Sixty patients with symptoms referable to disease of the
      vertebrobasilar system were examined with MR angiography and DSA. RESULTS: In
      patients with normal DSA results, all vertebral arteries (VAs) and basilar
      arteries (BAs) were also visualized with MR angiography. MR angiography
      demonstrated 117 of 120 superior cerebellar arteries and 80 of 90 posterior
      inferior cerebellar arteries but only 30 of 58 anterior inferior cerebellar
      arteries. MR angiography demonstrated disease of the VAs and BAs with 100%
      sensitivity. Stenoses were differentiated from occlusions in all cases. However,
      the degree of stenosis was overestimated in 63% of patients. In six patients with
      occlusive disease, collateral flow was correctly analyzed with selective
      saturation. CONCLUSION: Despite its limitations, MR angiography is a clinically
      important noninvasive technique for screening patients for macroangiopathy of the
      posterior arterial supply to the brain.

PMID- 8259385
TI  - Pregnancies after selective salpingography and tubal recanalization.

PMID- 8259386
TI  - Imaging of lymphoma with PET with 2-[F-18]-fluoro-2-deoxy-D-glucose: correlation
      with CT.
AB  - PURPOSE: To prospectively compare the accuracy of positron emission tomography
      (PET) with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) in imaging
      thoracicoabdominal lymphoma to that of computed tomography (CT). MATERIALS AND
      METHODS: Sixteen patients with lymphoma (11 with non-Hodgkin lymphoma [NHL] and
      five with Hodgkin disease) underwent FDG-PET and CT. Blinded, independent
      interpretations of PET and CT studies were followed by a direct comparison of the
      images. Measurement of tumor uptake of FDG was performed on positive PET studies.
      RESULTS: Fifty-four foci of abnormal uptake were detected with PET in 13
      patients. Forty-nine corresponding sites of lymphadenopathy and/or masses were
      detected with CT. All sites of adenopathy seen at CT were detected at PET. Three
      patients with Hodgkin disease had negative findings at abdominal PET, CT, and
      subsequent staging laparotomy. FDG uptake was comparable for both the low- and
      intermediate-grade lymphomas. CONCLUSION: These preliminary data indicate
      excellent accuracy for FDG-PET imaging of thoracicoabdominal lymphoma. All grades
      of NHL were successfully imaged with FDG-PET. PET appears to be a useful method
      for imaging lymphoma.

PMID- 8259387
TI  - Neural crest tumors: I-123 MIBG imaging in children.
AB  - PURPOSE: To determine 24- and 48-hour distribution of iodine-123
      metaiodobenzylguanidine (MIBG) and to establish an optimized pediatric imaging
      protocol. MATERIALS AND METHODS: Seventy-seven I-123 MIBG scans obtained in 33
      children undergoing evaluation for neural crest tumor were reviewed. RESULTS:
      Activity in the salivary glands, myocardium, liver, gut, and bladder was
      demonstrated on almost all scans. Activity was noted in the neck muscles, thyroid
      gland, and uninvolved adrenal gland in fewer studies. In 20 studies, abnormal
      uptake was present in the chest or abdomen at 24 and 48 hours, and lesion
      identification was improved at 48 hours in 12 studies. Detection of skeletal
      lesions on 14 scans was similar at 24 and 48 hours. Foci of tumor were first
      detected at I-123 MIBG imaging in nine studies, and in only two patients was
      tumor involvement initially missed on I-123 MIBG studies. CONCLUSION:
      Distribution of I-123 MIBG on images in children differs from that in earlier
      descriptions in adults. Images of the torso at 48 hours after injection are a
      useful adjunct in detection of lesions.

PMID- 8259388
TI  - Aryepiglottic fold width in patients with epiglottitis: where should measurements
      be obtained?
AB  - PURPOSE: To determine the best site for measurement or assessment of the
      aryepiglottic folds and determine whether evaluation of the lower portion of the
      folds is useful. MATERIALS AND METHODS: The lateral neck radiographs from 38
      children with epiglottitis were retrospectively reviewed and compared with
      findings in 100 patients with croup and 100 control patients. In all patients,
      the fold thickness was measured at three levels: at the midpoint (site 1), just
      behind the epiglottis (site 2), and at the base, just above the false vocal cords
      (site 3). RESULTS: Full-thickness measurements obtained at sites 1 and 2 were
      statistically significant predictors of epiglottitis (sensitivity, 94.74%;
      specificity, at least 96.50%) in comparison with those obtained in patients with
      croup and control patients. CONCLUSION: The best site for width assessment is the
      upper half of the folds. Measurement at the base, where the folds overlie the
      arytenoid cartilage, is not nearly as accurate and should be avoided.

PMID- 8259389
TI  - Nasojejunal feeding tube placement in children: four-year cumulative experience.
AB  - PURPOSE: Experience with fluoroscopically guided nasojejunal feeding tube
      placement in children was assessed regarding clinical diagnosis, fluoroscopy
      time, radiation dose, success rate, and placement failures. MATERIALS AND
      METHODS: From 1987 to 1991, 562 nasojejunal tubes were placed in 232 patients
      aged 1 week to 24 years (mean, 3 1/2 years) at the authors' institution. In every
      case, an 8-F feeding tube system was inserted. The fluoroscopy times and tube
      placement positions were evaluated in all cases. RESULTS: The mean fluoroscopy
      time was 5 minutes 30 seconds, which corresponded to an estimated mean midline
      fluoroscopy dose of 0.32 cGy. The tube was placed at or distal to the
      duodenojejunal junction in 543 attempts, for a success rate of 97%. The most
      common cause for unsuccessful tube placement was malrotation, with the
      fluoroscopic time and radiation dose significantly (P < .001) prolonged in these
      cases. CONCLUSION: Fluoroscopic guidance of placement of nasojejunal feeding
      tubes in children is successful, but the radiation exposure is not negligible and
      must be weighed against the need for nasojejunal feeding.

PMID- 8259390
TI  - Innominate artery compression of the trachea: relationship to cervical herniation
      of the normal thymus.
AB  - PURPOSE: To document the possible association of segmental tracheomalacia in the
      thoracic inlet with the combination of a large thymus and normal innominate
      artery. MATERIALS AND METHODS: Eight infants with symptoms of innominate artery
      compression of the trachea were studied. The diagnostic approach included
      observation of posterior tracheal displacement and focal tracheal collapse at
      fluoroscopy, ablation of the right radial pulse by rigid endoscopic pressure, and
      compression of the anterior tracheal wall by the innominate artery at magnetic
      resonance imaging. RESULTS: Six patients had relief of symptoms with either
      thymectomy and innominate artery reimplantation (n = 4) or subtotal thymectomy
      and innominate artery suspension (n = 2). The ratio of the sagittal diameter of
      the thymus to the sagittal diameter of the thoracic inlet was significantly (P <
      .0009) higher in the symptomatic patients (0.58 +/- 0.03) than in age-matched
      control subjects (0.35 +/- 0.08). CONCLUSION: Crowding of the thoracic inlet by
      cervical herniation of an enlarged but normal thymus may contribute to the
      development of tracheomalacia and the symptoms of innominate artery compression.

PMID- 8259391
TI  - Fallopian tube recanalization in an unrestricted patient population.
AB  - PURPOSE: To review the effectiveness of fallopian tube recanalization (FTR) when
      performed without restriction based on history or tubal condition. MATERIALS AND
      METHODS: From October 1989 to July 1992 in 37 consecutive women, aged 22-44 years
      (mean, 35 years), 42 FTRs were performed (five patients each underwent two FTRs).
      Water-soluble contrast material and selective ostial salpingography and/or
      microcatheter technique were used exclusively. Eighty tubes were evaluated, since
      four patients had previously undergone unilateral salpingectomy. Sixty-three
      tubes (79%) were occluded at the outset of the procedure. RESULTS: Complete
      recanalization was achieved in 45 of 63 (71%) occlusions. Adhesions were present
      in 25 of 80 (31%) tubes, salpingitis isthmica nodosa in 12 (15%), and
      hydrosalpinx in nine (11%). The 42 procedures resulted in 14 (33%) conceptions,
      nine (64%) of which involved pathologic tubes. Eleven intrauterine pregnancies
      resulted in five spontaneous first-trimester abortions, five full-term
      deliveries, and one continuing pregnancy. CONCLUSION: Favorable conception and
      live birth rates can be achieved with FTR, despite a high prevalence of tubal
      disease.

PMID- 8259392
TI  - Amyloidosis: the same cat, with different stripes.

PMID- 8259393
TI  - Fallopian tube disease: limited value of treatment with fallopian tube
      catheterization.
AB  - PURPOSE: Therapeutic role of fallopian tube catheterization was prospectively
      studied in patients with bilateral fallopian tube obstruction. MATERIALS AND
      METHODS: Catheterization was performed in 42 patients with bilateral obstruction;
      36 of the patients (67 fallopian tubes) underwent recanalization. RESULTS: Fifty
      two tubes with 54 proximal obstructions were successfully recanalized (technical
      success rate, 96%), 36 with selective catheterization and 16 with coaxial
      techniques. Among 13 tubes blocked at the distal portion of the tube, six tubes
      were negotiated. Perforation or subintimal injury occurred in three tubes, and
      one patient eventually had a tubal pregnancy. During follow-up of 3 months to 4
      years, five patients had conceived, including the patient with a tubal pregnancy
      and one patient who experienced spontaneous abortion during the first trimester.
      CONCLUSION: Fallopian tube catheterization is technically highly successful and
      diagnostically useful. However, its role in treating fallopian tube diseases is
      limited, and patients with distally blocked tubes are not good candidates for
      this procedure.

PMID- 8259394
TI  - Percutaneous fluoroscopically guided removal of dysfunctioning ureteral stents.
AB  - PURPOSE: To present the authors' experience with fluoroscopically guided
      percutaneous removal of dysfunctioning ureteral stents and to discuss the
      technique and instrumentation used. MATERIALS AND METHODS: Over 6 years, stent or
      stent fragment extraction procedures were performed in 20 patients. Indications
      included stent misplacement or migration, stent fracture, difficult retrograde
      exchange, stent occlusion, and removal prior to percutaneous ureteroscopy. Twelve
      extractions were performed as two-stage procedures and eight as one-stage
      procedures. A rigid forceps passed through a 12-F sheath was the preferred
      instrument for extraction. Other instruments used successfully included snares
      and flexible forceps. RESULTS: Seventeen procedures were successful: Eight stents
      were removed with rigid forceps, seven with flexible forceps, and two with
      snares. Three procedures were unsuccessful: In two, the stent could not be
      grasped because there was intervening renal pelvic mucosa, and in one, clotted
      blood surrounded the stent. There were no undue complications. CONCLUSION: This
      procedure is highly successful when appropriate technique and instruments are
      used.

PMID- 8259395
TI  - Renal corticomedullary differentiation: observation in patients with differing
      serum creatinine levels.
AB  - PURPOSE: To evaluate renal corticomedullary differentiation (CMD) in patients
      with differing serum creatinine (sCr) levels. MATERIALS AND METHODS: Ten patients
      with normal sCr levels (0.9-1.3 mg/dL [80-115 mumol/L]), 14 with mildly elevated
      levels (1.5-2.9 mg/dL [133-256 mumol/L]), and 15 with elevated levels (> 3.0
      mg/dL [265 mumol/L]) were examined with unenhanced T1-weighted fat-suppressed
      spin-echo (T1FS) and immediate gadolinium-enhanced gradient-echo (Gd-GRE)
      imaging. RESULTS: Patients with normal sCr levels had CMD on T1FS and Gd-GRE
      images. Among patients with mildly elevated levels, seven did and seven did not
      have CMD on T1FS images; all had CMD on Gd-GRE images. Patients with elevated
      levels had no CMD on T1FS images; 13 had CMD on Gd-GRE images. Two patients with
      levels above 10.0 mg/dL (884 mumol/L) had no CMD on Gd-GRE images. CONCLUSION:
      Independent of the cause of elevated sCr level, levels above 3.0 mg/dL result in
      loss of CMD on T1FS images, while levels above 10.0 mg/dL result in loss of CMD
      on Gd-GRE images.

PMID- 8259396
TI  - Captopril renography and the hypertensive renal transplantation patient: a
      predictive test of therapeutic outcome.
AB  - PURPOSE: To detect predictive accuracy of captopril renography in transplant
      recipients with hypertension. MATERIALS AND METHODS: This prospective study was
      performed to evaluate findings on 18 renal scans acquired after administration of
      captopril (captopril renograms) in 14 transplantation patients with new-onset or
      poorly controlled hypertension. Captopril renography was not used to affect case
      management but to predict response to angioplasty. RESULTS: Arteriograms were
      abnormal in 12 of 18 studies. In the six cases in which angiograms were normal,
      captopril renograms also were normal. In the 12 cases in which angiograms were
      abnormal, captopril renograms were normal in five and abnormal in seven. In the
      five cases in which renograms were normal, hypertension did not improve, although
      angioplasty was technically successful. In the seven with abnormal renograms,
      four patients underwent angioplasty with excellent results. These patients had a
      significant (P < .05) decrease in diastolic blood pressure (-15 mm Hg) and in
      creatinine concentration (-0.4 mg/dL) compared with patients with normal
      renograms and abnormal angiograms. CONCLUSION: In this small population,
      captopril renography appeared to be predictive of physiologically meaningful
      renal artery stenosis.

PMID- 8259397
TI  - Diagnosis of dissecting hematoma of the aorta: a choice between good and better.

PMID- 8259398
TI  - Effect of magnetic susceptibility contrast medium on myocardial signal intensity
      with fast gradient-recalled echo and spin-echo MR imaging: initial experience in
      humans.
AB  - PURPOSE: To show the effect of dysprosium diethylenetriaminepentaacetic acid bis
      methylamine injection on the images of normal human myocardium. MATERIALS AND
      METHODS: T2-sensitive fast gradient-recalled echo (GRE) (repetition time [TR],
      10.8 msec; echo time [TE], 4.2 msec) and spin-echo (SE) (TR, three RR intervals;
      TE, 60 msec) magnetic resonance (MR) imaging with driven equilibrium-preparation
      pulse was used to produce T2 contrast material enhancement. The contrast agent
      was injected into 12 healthy subjects at doses of 0.05, 0.1, 0.2, 0.4, and 0.6
      mmol/kg. RESULTS: Driven equilibrium-prepared GRE images showed a transient
      decrease of myocardial signal intensity at doses of 0.2-0.6 mmol/kg. Postcontrast
      T2-weighted SE images showed a myocardial signal attenuation (30%-45% decrease)
      at a dose of 0.4 mmol/kg or higher. CONCLUSION: Dynamic MR imaging with a
      magnetic susceptibility contrast medium can be used to monitor the first pass of
      contrast media through human myocardium with a conventional MR imager and a fast
      GRE sequence.

PMID- 8259399
TI  - Aortic cobwebs: an anatomic marker identifying the false lumen in aortic
      dissection--imaging and pathologic correlation.
AB  - PURPOSE: To describe and estimate the frequency of fibroelastic cords or bands
      projecting from the false lumen wall ("aortic cobwebs") in acute and chronic
      dissections. MATERIALS AND METHODS: Pathologic specimens (n = 23), routine
      magnetic resonance (MR) images (n = 27), and intravascular (n = 5) and
      transesophageal (n = 3) ultrasound (US) images from 43 patients with aortic
      dissection were reviewed, and the presence and configuration of cobwebs were
      noted. RESULTS: Aortic cobwebs usually bridge the junction of the dissection flap
      with the outer wall of the false lumen (the line of dissection) but occasionally
      project like small tendrils from the false lumen wall remote from the line of
      dissection. Cobwebs were found in 17 of 23 pathologic specimens and on six of 27
      MR images, two of five intravascular US scans, and one of three transesophageal
      US scans. CONCLUSION: Aortic cobwebs most likely represent residual ribbons of
      media that have been incompletely sheared from the aortic wall during the
      dissection process. As such, they can serve as an anatomic marker of the false
      lumen. They are occasionally seen on routine aortic images and may, therefore,
      prove useful for orientation during percutaneous or surgical interventional
      procedures to relieve ischemic complications of aortic dissection.

PMID- 8259400
TI  - Chronic mesenteric ischemia: evaluation with phase-contrast cine MR imaging.
AB  - PURPOSE: To compare superior mesenteric artery (SMA) blood flow in healthy
      volunteers and patients with stenoses in the fasting state and after food intake
      by using phase-contrast (PC) cine magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: Ten healthy subjects, four asymptomatic patients (three with 50%
      stenosis, one with 70% stenosis), and one symptomatic patient (with 80% stenosis)
      were studied. All subjects were studied after fasting at least 8 hours and 15,
      30, and 45 minutes after ingesting a standard meal. RESULTS: In healthy
      volunteers, SMA blood flow at all postprandial intervals increased significantly
      compared with that obtained after fasting (P < or = .0005). The percentage change
      in SMA blood flow 30 minutes after food intake provided the best distinction
      between the healthy subjects, the asymptomatic patients, and the symptomatic
      patient. CONCLUSION: Cine PC MR imaging is an effective, noninvasive technique
      for measuring SMA blood flow.

PMID- 8259401
TI  - US-assisted bronchoscopy: is seeing believing?

PMID- 8259402
TI  - Spiral CT of renal artery stenosis: comparison of three-dimensional rendering
      techniques.
AB  - PURPOSE: To evaluate the accuracy of computed tomographic (CT) angiography in the
      detection of renal artery stenosis (RAS). MATERIALS AND METHODS: CT angiography
      was performed in 31 patients undergoing conventional renal arteriography. CT
      angiographic data were reconstructed with shaded surface display (SSD) and
      maximum-intensity projection (MIP). Stenosis was graded with a four-point scale
      (grades 0-3). The presence of mural calcification, poststenotic dilatation, and
      nephrographic abnormalities was also noted. RESULTS: CT angiography depicted all
      main (n = 62) and accessory (n = 11) renal arteries that were seen at
      conventional arteriography. MIP CT angiography was 92% sensitive and 83% specific
      for the detection of grade 2-3 stenoses (> or = 70% stenosis). SSD CT angiography
      was 59% sensitive and 82% specific for the detection of grade 2-3 stenoses. The
      accuracy of stenosis grading was 80% with MIP and 55% with SSD CT angiography.
      Poststenotic dilatation and the presence of an abnormal nephrogram were 85% and
      98% specific, respectively. CONCLUSION: CT angiography shows promise in the
      diagnosis of RAS. The accuracy of CT angiography varies with the three
      dimensional rendering technique employed.

PMID- 8259403
TI  - Embolization therapy of congenital arteriovenous malformations: use of alternate
      approaches.
AB  - PURPOSE: To present results of embolization therapy performed with use of
      alternate approaches in 22 patients with peripheral congenital vascular
      malformations in whom lesion anatomy precluded effective use of conventional
      transfemoral catheter techniques. MATERIALS AND METHODS: Eleven patients had high
      flow fistulous arteriovenous malformations and 11 had hemangiomatous vascular
      malformations. The alternate approaches employed were direct injection of embolic
      materials into the malformation or into central vessels of the lesion under
      fluoroscopic guidance and (in four cases) selective catheterization and
      embolization of abnormal veins draining arteriovenous malformations. The primary
      embolic agent combination used consisted of polyvinyl alcohol particles, sodium
      tetradecyl sulfate, microfibrillar collagen, and ethanol. RESULTS: Use of
      alternate approaches resulted in effective symptomatic control in 10 of 11
      patients (91%) with hemangiomatous lesions and seven of 11 (64%) with high-flow
      arteriovenous malformations. CONCLUSION: Use of alternate approaches to such
      vascular malformations extends the use of embolization therapy.

PMID- 8259404
TI  - Iliac artery stent placement: clinical experience with a nitinol stent.
AB  - PURPOSE: To determine the effectiveness of a prototype nitinol stent in the iliac
      arteries. MATERIALS AND METHODS: Fourteen patients with arteriosclerotic lesions
      of the iliac arteries (nine stenoses, five occlusions) were treated
      percutaneously with a prototype nitinol vascular stent (Cragg stent) after
      unsuccessful percutaneous transluminal angioplasty. RESULTS: In 13 patients
      available for follow-up, the mean ankle-brachial index (ABI) increased from 0.4
      +/- 0.32 (standard deviation) before the procedure to 0.81 +/- 0.27 after the
      procedure (P < .01). After 6, 12, and 24 months, the mean ABI was 0.97 +/- 0.2,
      0.87 +/- 0.15, and 0.89 +/- 0.1, respectively. In two patients, radial stiffness
      of the stent was too low to completely eliminate a high-grade, calcified
      stenosis; long-term patency of the vessel, however, was preserved. In all other
      patients, stent placement achieved good vascular reconstitution. No stent
      occlusion or restenosis was observed. CONCLUSION: The results with the Cragg
      stent were similar to those with other commercially available stents. These
      preliminary results require confirmation with a larger series.

PMID- 8259405
TI  - Breast cancer in the elderly patient: early detection with mammography.
AB  - PURPOSE: To determine the mammographic features and differences in stage of
      breast carcinomas in elderly women with malignancies detected with palpation or
      mammography at presentation. MATERIALS AND METHODS: The mammograms and clinical
      records of 60 patients (aged 75 years or older) with 62 breast carcinomas,
      detected during 40 consecutive months, were retrospectively reviewed. A variety
      of dedicated devices and processing equipment were used. The histologic features,
      mammographic appearance, mode of detection, and stage of disease were determined.
      Statistically significant differences between subgroups were calculated with the
      Student t and chi 2 tests. RESULTS: Sixty cancers (97%) were seen on mammograms.
      Seventeen tumors detected with annual mammography differed significantly from the
      45 carcinomas in nonscreened patients in diameter (1.1 vs 2.1 cm; P < .0005) and
      stage (14 minimal [82%] of 17 tumors vs 15 minimal [33%] of 45 tumors; P <
      .0005). Thirty-five nonpalpable malignancies differed significantly from 27
      palpable masses in diameter (1.2 vs 2.3 cm; P = .01) and stage (25 tumors minimal
      [71%] vs four tumors minimal [15%]; P < .0005). CONCLUSION: Screening mammography
      enabled detection of statistically significantly smaller and earlier-stage
      tumors, most of which were minimal disease.

PMID- 8259406
TI  - Current practice of screening mammography in the United States: data from the
      National Survey of Mammography Facilities.
AB  - PURPOSE: To describe the extent to which screening mammography (SCM) has been
      organized according to the public health concept of low-cost, high-quality, and
      population-based screening, selected indicators of U.S. mammography facilities
      were evaluated. MATERIALS AND METHODS: Data from the National Cancer Institute's
      phase I of the National Survey of Mammography Facilities were analyzed. This data
      base consists of questionnaire information obtained in 1992 from a 10% random
      sample of U.S. mammography facilities. RESULTS: Of 1,057 facilities, 634 (60%)
      distinguished SCM from diagnostic mammography (DXM). In facilities providing SCM
      (n = 535), 477 (89%) used the mediolateral oblique (MLO) view and/or the
      craniocaudal (CC) view. While 898 (85%) of all facilities requested clinical
      follow-up of abnormal mammograms, only 285 (27%) facilities actually received
      this information. Only 137 (13%) facilities operated at high volume (> or = 15
      mammograms per day per machine), and 211 (20%) used batch interpretation. Average
      cost of a screening mammogram was $89 (range, $10-$225). CONCLUSIONS: While more
      facilities are distinguishing SCM from DXM and obtain MLO and CC views, SCM does
      not appear to be organized for high volume and low cost.

PMID- 8259407
TI  - Diagnostic accuracy, patient outcome, and economic factors in lumbar
      radiculopathy.

PMID- 8259408
TI  - Needle core biopsy guided with mammography: a study of cost-effectiveness.
AB  - PURPOSE: To analyze the cost-effectiveness of needle core biopsy (NCB) in a
      breast cancer screening program. MATERIALS AND METHODS: A computer model was used
      to compare two hypothetical groups of women: those who undergo annual
      mammographic screening and those observed without screening. All clinically
      significant outcomes for each group were included in the model, which reflected
      the state of a woman's health each year beginning at age 40 years and ending at
      age 85 years. RESULTS: The marginal cost per year of life saved by screening was
      reduced a maximum of 23% (from $20,770 to $15,934) with use of NCB instead of
      surgical biopsy. The cost of NCB had less effect on cost-effectiveness than the
      number of women who underwent NCB. CONCLUSION: When used for the same indications
      as surgical biopsy, NCB substantially reduces the cost of a breast cancer
      screening program.

PMID- 8259409
TI  - Radiography of microcalcifications in stereotaxic mammary core biopsy specimens.
AB  - PURPOSE: To describe the technique of specimen radiography in stereotaxically
      guided core biopsies and evaluate its role in detection and diagnosis of
      microcalcifications in breast tissue. MATERIALS AND METHODS: Specimens from 361
      stereotaxic breast core biopsies of 72 nonpalpable lesions with mammographic
      evidence of microcalcifications were obtained from 65 patients. Specimens were
      placed in saline on microscope slides and radiographed. RESULTS:
      Microcalcifications were detected radiographically in 146 of 361 (40%) cores. If
      calcifications were present on specimen radiographs, histologic detection of
      these calcifications was made in 114 of 146 (78%) specimens, and diagnosis was
      made in 118 of 146 (81%). If calcifications were not present on specimen
      radiographs, histologic detection was obtained in 27 of 215 (13%) specimens and
      specific diagnosis in 81 of 215 (38%). CONCLUSION: Specimen radiography should be
      routinely performed in stereotaxic core biopsies of breast microcalcifications to
      ensure appropriate tissue has been obtained and to direct pathologic diagnosis of
      the tissue specimens.

PMID- 8259410
TI  - Silicone breast implant ruptures in an animal model: comparison of mammography,
      MR imaging, US, and CT.
AB  - PURPOSE: To determine the most accurate imaging modality for detection of
      silicone implant ruptures. MATERIALS AND METHODS: Forty single-lumen silicone
      implants were surgically placed in 20 rabbits. Each rabbit received one intact
      and one ruptured implant and was examined with mammography, magnetic resonance
      (MR) imaging, ultrasound (US), and computed tomography (CT). Five radiologists
      reviewed all images in a random fashion and graded each for rupture. The
      radiologist who performed US also graded her impression during examination with
      US. Receiver operating characteristic (ROC) analysis was performed. RESULTS: MR
      imaging and CT were the most accurate modalities in detection of implant
      ruptures, with areas under the ROC curves (Az) of .95 and .91. Mammography and US
      were statistically significantly inferior, with Az of .77 for each (P < .05).
      CONCLUSION: MR imaging and CT are statistically more accurate than US and
      mammography for detection of intracapsular silicone implant ruptures when only
      the images are reviewed.

PMID- 8259411
TI  - US-assisted bronchoscopy with use of miniature transducer-containing catheters.
AB  - PURPOSE: To demonstrate the value of ultrasound (US) guidance during flexible
      bronchoscopic procedures in a series of patients with known or suspected
      pulmonary neoplasms. MATERIALS AND METHODS: US-guided bronchoscopy was carried
      out as an adjunct to conventional bronchoscopy for the diagnosis of mediastinal,
      hilar, or parenchymal neoplasms in 25 patients with masses previously detected
      with chest radiography or computed tomography. Miniature transducer-containing
      catheters were inserted through the biopsy port of the flexible bronchoscope, and
      cross-sectional real-time US scans of tumors, lymph nodes, and blood vessels were
      obtained. RESULTS: Among six cases of peripheral masses and 19 cases of central
      masses, additional information was provided in 18 cases (72%). This information
      was used to choose the optimal site for transmural biopsy. CONCLUSION: These
      preliminary results suggest that this US procedure may become an important
      diagnostic tool during bronchoscopy, due to the ability to identify structures
      beyond the lumen of the tracheobronchial tree.

PMID- 8259412
TI  - Preoperative staging of non-small cell lung cancer: transesophageal US-guided
      fine-needle aspiration biopsy of mediastinal lymph nodes.
AB  - PURPOSE: To evaluate the usefulness of transesophageal real-time ultrasound (US)
      guided fine-needle aspiration biopsy (FNAB) in staging non-small cell lung
      carcinoma. MATERIALS AND METHODS: Two patients (a 64-year-old man and a 48-year
      old woman) with non-small cell lung carcinoma and mediastinal lymphadenopathy
      detected at computed tomography underwent preoperative evaluation with
      transesophageal real-time US-guided FNAB. Two aspirates were obtained from each
      patient. RESULTS: Diagnostic tissue from a contralateral posterior mediastinal
      lymph node was obtained from the first aspirate in each case. Neither patient
      experienced a complication as a result of this technique, and both were
      subsequently referred for palliative therapy in light of these findings.
      CONCLUSION: Real-time US-guided FNAB is useful in the preoperative staging of
      disease in selected patients with non-small cell lung cancer.

PMID- 8259413
TI  - CT-guided biopsy of the chest: usefulness of fine-needle core biopsy combined
      with frozen-section pathologic diagnosis.
AB  - PURPOSE: To improve the diagnostic accuracy of computed tomography (CT)-guided
      biopsy of the chest. MATERIALS AND METHODS: The usefulness of fine-needle core
      biopsy combined with immediate frozen-section diagnosis by pathologists was
      prospectively studied. Fifty-five biopsies of the chest were performed under CT
      guidance in 55 patients with 36 malignant and 19 benign processes. Initial biopsy
      was always attempted with a 21-gauge modified Menghini needle; tissue samples
      were sent to the pathology department immediately after biopsy for pathologic
      diagnosis of the frozen sections. RESULTS: In 47 of 55 lesions (85%) sufficient
      materials for diagnosis were obtained and enabled correct final diagnosis.
      Specific histologic diagnosis was possible in 25 (74%) of 34 malignant and 10
      (77%) of 13 benign lesions. In all of the eight other lesions, cytologic
      diagnosis of aspirated material was correct. No false-positive or false-negative
      results have occurred. CONCLUSION: Histologic diagnosis with frozen sections
      improves diagnostic accuracy of chest biopsy; immediate pathologic diagnosis is
      an encouraged adjunct.

PMID- 8259414
TI  - Acute lung disease in the immunocompromised host: CT and pathologic examination
      findings.
AB  - PURPOSE: To compare findings at computed tomography (CT) and pathologic
      examination in immuno-compromised patients with acute lung disease. MATERIALS AND
      METHODS: Findings in 33 chest CT scans were compared with findings in pathologic
      specimens obtained at open lung biopsy (n = 29) or autopsy (n = 4) in 32
      patients, aged 17-64 years. RESULTS: Nodules were the main abnormality at CT in
      14 cases. Pathologically, the 14 nodules were due to infection (n = 10),
      bronchiolitis obliterans organizing pneumonia (BOOP) (n = 3), or lymphoma (n =
      1). Areas of ground-glass attenuation were the main finding in 15 patients. These
      areas were a result of BOOP (n = 4), cytotoxic drug reaction (n = 4), infection
      (n = 4), lymphoma (n = 2), or nondiagnostic biopsy (n = 1). Consolidation was the
      main finding in four cases, being seen with BOOP (n = 2), infarction due to
      fungal infection (n = 1), and diffuse pulmonary hemorrhage (n = 1). CONCLUSION:
      The pattern at CT accurately reflected the gross morphologic features seen in the
      pathologic specimens. Nodules were usually inflammatory lesions, often
      infections, and open lung biopsy usually revealed their specific origin.

PMID- 8259415
TI  - Frequency and management of pneumothoraces in heart-lung transplant recipients.
AB  - PURPOSE: To determine the frequency and describe the clinical relevance of
      simultaneous bilateral pneumothoraces in heart-lung transplant recipients.
      MATERIALS AND METHODS: The chest radiographs in 72 consecutive heart-lung
      transplant recipients were retrospectively reviewed. The study group consisted of
      15 patients with a pneumothorax that occurred after removal of surgically placed
      drainage tubes and subsequent complete expansion of both lungs. RESULTS:
      Simultaneous bilateral pneumothoraces occurred in six patients (40%); 10 episodes
      of unilateral pneumothorax occurred in nine patients (60%). Causes of
      pneumothoraces included transthoracic fine-needle biopsy (n = 5), bronchoscopic
      biopsy (n = 3), placement of a central venous catheter (n = 3), and thoracentesis
      (n = 3); no cause was found in two cases. CONCLUSION: Physicians who perform
      transthoracic interventions in this patient population should be aware of the
      likelihood of persistent pleural communications and the possibility of
      potentially life-threatening bilateral pneumothoraces.

PMID- 8259416
TI  - Hemarthrosis and synovitis associated with hemophilia: clinical use of P-32
      chromic phosphate synoviorthesis for treatment.
AB  - PURPOSE: To evaluate the clinical usefulness of phosphorus-32 chromic phosphate
      synoviorthesis in patients with hemophilia, recurrent hemarthrosis, and
      synovitis. MATERIALS AND METHODS: Forty-four P-32 colloid synoviorthesis
      procedures were performed in 38 patients with these abnormalities. P-32 colloid
      was injected intramuscularly in a dose of 1.0 mCi (37.0 MBq) in adult knees and
      0.5 mCi (18.5 MBq) in adult elbows. A thin-window Geiger-Muller counter was used
      to survey treated joints, lymph nodes, and liver in order to detect leakage from
      the joint. Follow-up extended to a maximum of 4 years after treatment. RESULTS:
      No evidence of clinically significant leakage was seen. Twenty-two of 28
      treatments (78%) with longer than 6 months follow-up were associated with
      improvement in range of motion and frequency of hemorrhage. Of 15 treatments with
      longer than 2 years follow-up, 10 (67%) were associated with improvement in range
      of motion; 12 (80%), with improvement in frequency of hemorrhage; and 12 (80%)
      with improvement in quality-of-life activities. CONCLUSION: P-32 colloid
      synoviorthesis is a clinically useful out-patient procedure in patients with
      hemophilia, recurrent hemarthrosis, and synovitis in whom hemostatic therapy has
      failed.

PMID- 8259417
TI  - MR imaging in the follow-up of malignant and aggressive soft-tissue tumors:
      results of 511 examinations.
AB  - PURPOSE: To present magnetic resonance (MR) imaging findings from 511 follow-up
      examinations of aggressive soft-tissue tumors. MATERIALS AND METHODS: One hundred
      eighty-two patients with aggressive soft-tissue tumours underwent postoperative
      T1- and T2-weighted imaging; 41 also underwent 51 gadolinium-enhanced T1-weighted
      examinations, and five underwent dynamic gadolinium-enhanced subtraction imaging.
      RESULTS: Twenty-four of 25 patients (101 of 102 examinations) without high signal
      intensity (HSI) at T2-weighted imaging had no recurrence. Among 79 patients (321
      examinations) who demonstrated HSI without a mass, only two tumors recurred
      within 1 year. An HSI mass was found in 88 studies of 78 patients and represented
      recurrence (n = 60), hygroma (n = 24), or a radiation-induced pseudomass (n = 4).
      Hygromas did not enhance, while recurrences enhanced at 1-3 minutes and
      postirradiation change enhanced at 4-7 minutes. CONCLUSION: T2-weighted imaging
      can be used to identify possible recurrence of aggressive soft-tissue tumors,
      while gadolinium-enhanced imaging can be used to differentiate recurrences from
      hygromas and inflammatory change.

PMID- 8259418
TI  - MR imaging and spectroscopy for prognostic evaluation in soft-tissue sarcomas.
AB  - PURPOSE: To enable prediction of tumor response to a particular treatment.
      MATERIALS AND METHODS: The authors studied the value of hydrogen-1 T2 and
      phosphorus-31 magnetic resonance (MR) spectroscopic metabolic determinations as
      indicators of prognosis in 20 humans and 10 dogs with soft-tissue sarcomas. All
      patients underwent combined fractionated radiation therapy and hyperthermia.
      Surgical resection of the entire tumor in humans allowed comparison of pretherapy
      T2 and MR spectroscopic parameters with subsequent histologic findings. Long-term
      clinical follow-up (no surgical intervention) was available with the dogs and
      allowed comparison of pretherapy pH with the duration of local relapse-free
      survival. RESULTS: A relationship exists between pretherapy pH and T2 and
      ultimate tumor necrosis in humans and pretherapy pH and time elapsed until local
      failure in dogs. CONCLUSION: MR imaging and spectroscopy could be useful in the
      prognosis of patients with soft-tissue sarcomas before therapy is initiated.

PMID- 8259419
TI  - Soft-tissue tumors: diagnosis with Tc-99m (V) dimercaptosuccinic acid
      scintigraphy.
AB  - PURPOSE: To assess the potential of technetium-99m (V) dimercaptosuccinic acid
      (DMSA) scintigraphy for diagnosis of soft-tissue tumors. MATERIALS AND METHODS:
      Tc-99m (V) DMSA scintigraphy was performed in 76 patients with histologic proof
      of soft-tissue tumors. In 57 of these patients, gallium-67 citrate scintigraphy
      was performed within 2 weeks after Tc-99m (V) DMSA scintigraphy. RESULTS: Uptake
      of Tc-99m (V) DMSA was clearly detected in almost all sarcomas, metastatic
      carcinomas, highly recurrent benign tumors (ie, extra-abdominal desmoids and
      tenosynovial giant cell tumors), superficial and deep hemangiomas, and
      granulomatous soft-tissue lesions but was not found in other benign solid tumors
      of soft tissue. Uptake of Ga-67 citrate was clearly detected in all inflammatory
      lesions and metastatic carcinomas, eight of 14 sarcomas (57%), and two of 10
      highly recurrent benign tumors (20%) but was not found in hemangiomas or benign
      soft-tissue tumors. CONCLUSION: Low-grade malignant and highly recurrent benign
      lesions, which often recur after surgery, were detected more accurately with Tc
      99m (V) DMSA scintigraphy than with Ga-67 citrate scintigraphy.

PMID- 8259420
TI  - Credentialing of crossover privileges in fluoroscopy for nonradiologists.
AB  - PURPOSE: To comply with federal and state guidelines, a credentialing process was
      developed for nonradiologist medical users of fluoroscopy. MATERIALS AND METHODS:
      Seventy-three nonradiologist physicians participated in a program consisting of
      (a) an introductory 1-hour lecture; (b) a 10-page booklet providing basic
      information on radiation physics, radiobiology, and radiation safety; and (c)
      successful completion of a 15-question self-study quiz on fluoroscopy RESULTS:
      Mean fluoroscopy times per surgical case were compared for a 7-month period
      before (7.01 minutes in 201 cases) and after (4.39 minutes in 396 cases) the
      program and showed a 37.4% decrease (P < .05). Participating physician attitudes
      were surveyed at the completion of the program and showed an average physician
      time investment of 2 1/2 hours and a 4.1 approval rating for the credentialing
      program on a 5-point Likert scale. CONCLUSION: This fluoroscopic credentialing
      process for nonradiologist medical users (a) achieved a statistically significant
      reduction in fluoroscopic time per surgical case, (b) required a minimal
      investment of physician time, and (c) was well received by the medical staff.

PMID- 8259421
TI  - Diagnostic reading session: temporal patterns and case-order effects.
AB  - The authors analyzed receiver-operating-characteristic studies to determine
      temporal patterns and performance as a function of the elapsed time in a reading
      session. Nineteen radiologists each read as many as 300 chest images with use of
      seven different display modalities, including conventional and laser-printed film
      and high-resolution soft display. With a computerized reporting system, the ratio
      of observers' interpretation rates (time to diagnosis) were recorded for the last
      five and 10 compared with the first five and 10 of 30-40 cases seen in sessions
      lasting 45-110 minutes. Observers tended to accelerate their interpretation as
      the sessions progressed by an average of 15% (P < .001). The acceleration was
      consistent for all readers (both fast and slow) with a variety of display modes
      under the nonrestricted time environment.

PMID- 8259422
TI  - Mammographic follow-up to detect breast cancer recurrence after conservative
      treatment.

PMID- 8259423
TI  - Acute appendicitis: CT and US correlation in 100 patients.
AB  - PURPOSE: To compare the accuracy of computed tomography (CT) and ultrasonography
      (US) in the diagnosis of acute appendicitis. MATERIALS AND METHODS: One hundred
      consecutive patients were examined with US and CT, and the results, independently
      reported, were correlated with surgical and histopathologic findings (69
      patients) and data from other laboratory and clinical follow-up (31 patients).
      RESULTS: Fifty-four patients had acute appendicitis; 46 patients did not.
      Analysis of the data for CT and US, respectively, revealed sensitivity, 96%
      versus 76%; specificity, 89% versus 91%; accuracy, 94% versus 83%; positive
      predictive value, 96% versus 95%; and negative predictive value, 95% versus 76%.
      In the 46 patients without appendicitis, an alternative diagnosis was made with
      CT in 22 patients and with US in 15. CT scans showed abscesses and/or phlegmons
      in 28% of patients with appendicitis versus 17% at US. Results of CT and US were
      discordant in 20 patients; CT findings were correct in 17 and US findings in
      three. CONCLUSION: CT is more accurate than US in diagnosis of acute
      appendicitis.

PMID- 8259424
TI  - Gastrointestinal amyloidosis: radiologic features by chemical types.
AB  - PURPOSE: To determine the correlation between the radiographic and histologic
      findings of amyloidosis according to chemical type of amyloid protein. MATERIALS
      AND METHODS: The 49 patients with amyloidosis were examined radiographically, and
      gastrointestinal tract biopsy specimens were studied histologically. RESULTS:
      Considerable differences were found between amyloid proteins. On
      immunohistochemical studies, amyloid A produced a coarse mucosal pattern with
      innumerable fine granular elevations, which reflected expansion of the lamina
      propria by amyloid deposits. Polypoid protrusions and invariable thickening of
      the folds were evident only in light chain protein, correlating with massive
      amyloid deposits in the muscularis mucosae and submucosa. beta 2-Microglobulin
      produced marked delay in transit time and dilatation of the small and large
      intestines, relating to extensive amyloid deposits in the muscularis propria. The
      prevalence of these radiographic changes was highest in the small intestine for
      every chemical type. CONCLUSION: Characteristic radiographic changes of each
      chemical type of amyloid protein can be detected well in the small intestine.

PMID- 8259425
TI  - Determination of optimal time window for liver scanning with CT during arterial
      portography.
AB  - PURPOSE: To determine the optimal time window for scanning the liver with
      computed tomography (CT) during arterial portography (CTAP). MATERIALS AND
      METHODS: After vasodilation and contrast medium injection into the superior
      mesenteric artery (80 mL at 5 mL/sec), 25 repeated scans were obtained at a
      single level within 83 seconds in 13 patients. Attenuation was measured on every
      scan, and time-attenuation curves were created. Enhancement characteristics of
      the portal vein, liver parenchyma, aorta, and tumors were evaluated. RESULTS:
      Parenchymal enhancement of more than 60 HU was achieved between 18 seconds +/- 4
      (standard deviation) and 67 seconds +/- 15, and high parenchyma-to-tumor contrast
      of more than 50 HU occurred between 18 seconds +/- 3 and 62 seconds +/- 14.
      CONCLUSION: To scan the liver within such a narrow time window, a spiral CT
      technique is necessary. When the above injection parameters are used in CTAP, the
      spiral CT sequence should be started 20 seconds after the beginning of the
      injection.

PMID- 8259426
TI  - Peripheral washout: a sign of malignancy on dynamic gadolinium-enhanced MR images
      of focal liver lesions.
AB  - PURPOSE: To assess the value of peripheral washout of contrast medium in
      differentiating benign from malignant focal liver lesions. MATERIALS AND METHODS:
      One hundred two patients, 49 with malignant liver tumors and 53 with benign
      lesions, underwent unenhanced T1- and T2-weighted and dynamic gadolinium-enhanced
      magnetic resonance (MR) imaging. Dynamic contrast material-enhanced MR imaging
      was performed before and up to 10 minutes after intravenous administration of a
      bolus of gadopentetate dimeglumine (0.1 mmol/kg). RESULTS: On the dynamic
      contrast-enhanced images, 12 of the 49 malignant tumors had a rim that was hypo
      intense to the center of the lesion ("peripheral washout" sign); this rim was
      best seen 10 minutes after administration of contrast material. This sign was
      absent in the remaining 37 malignant tumors as well as in all 53 benign lesions
      (P < .001). The peripheral washout sign had a sensitivity of 24.5% and a
      specificity of 100% in the diagnosis of malignancies of the liver. The malignant
      tumors with peripheral washout showed no difference in signal intensity between
      the periphery and the center on the unenhanced T1- and T2-weighted images.
      CONCLUSION: Peripheral washout is a specific sign of malignancy in dynamic
      gadolinium-enhanced MR imaging of liver lesions.

PMID- 8259427
TI  - The radiologist: a middleman (person) or medicine.

PMID- 8259428
TI  - Percutaneous hot saline injection therapy for hepatic tumors: an alternative to
      percutaneous ethanol injection therapy.
AB  - PURPOSE: To evaluate the usefulness of percutaneous hot saline injection therapy
      (PSIT) in the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS:
      Twenty patients with HCC (23 nodules) underwent PSIT. Mean tumor diameter was <
      or = 30 mm. PSIT was performed by injecting hot saline into the HCC. The
      therapeutic effect of PSIT was evaluated with computed tomography, angiography,
      measurement of alpha-fetoprotein levels, and histopathologic examination of
      needle biopsy and resected specimens. RESULTS: No complications were encountered,
      and a therapeutic effect was obtained in all cases. When the injected material
      cools, it becomes physiologic saline making it possible to inject relatively
      large volumes in a single session. CONCLUSION: PSIT has promise as a form of
      curative local therapy for small HCCs and is expected to exert a safe and
      favorable therapeutic effect on large HCCs as well.

PMID- 8259429
TI  - Adrenocorticotropic hormone--secreting islet cell tumors: are they always
      malignant?
AB  - PURPOSE: To evaluate the frequency with which benign occult islet cell tumors
      cause ectopic adrenocorticotropic hormone (ACTH) syndrome. MATERIALS AND METHODS:
      Ten patients with Cushing syndrome due to the production of ACTH by a pancreatic
      islet cell tumor were studied. In addition, 53 cases of ACTH-secreting islet cell
      tumors in the English-language literature were reviewed. RESULTS: All 10 of the
      authors' patients had malignant islet cell tumors. Liver metastases were present
      in all 10 patients at presentation. Five patients are dead, four patients are
      alive with liver metastases, and one patient is alive without gross evidence of
      residual tumor after distal pancreatectomy and right hepatectomy. Eight of the 10
      islet cell carcinomas produced gastrin in addition to ACTH. In the 53 reported
      cases of ectopic ACTH production, there was only one benign adenoma with a
      prolonged follow-up. CONCLUSION: When ectopic ACTH production is caused by an
      islet cell tumor, the tumor is large and malignant and has usually metastasized
      to the liver by the time Cushing syndrome is diagnosed. No occult ACTH-producing
      islet cell tumor was encountered in the authors' experience or in a review of the
      literature.

PMID- 8259430
TI  - Splenic vein thrombosis after splenectomy: frequency and role of imaging.
AB  - PURPOSE: To assess the frequency of splenic vein thrombosis (SVT) after
      splenectomy and its consequences on patient treatment. MATERIALS AND METHODS: A
      group of 183 consecutive patients who underwent splenectomy were evaluated. Of
      these patients, 119 underwent postoperative ultrasound (US) or computed
      tomography. RESULTS: SVT was diagnosed in 13 of 119 patients in the first 2 weeks
      after surgery. In these 13 patients, splenectomy had been performed for
      hematologic disorders (n = 12) or trauma (n = 1). Seven of the 13 patients were
      asymptomatic. After anticoagulant therapy, follow-up US of 12 patients showed
      resolution of thrombosis with no complications in 10 patients; two patients
      developed cavernous transformation of the portal vein. CONCLUSION: Since only 65%
      of patients underwent imaging, the true frequency of SVT could not be determined;
      however, it occurred in at least 7% of patients who underwent splenectomy.
      Routine Doppler US should be performed after splenectomy to allow early
      anticoagulant therapy in patients with SVT.

PMID- 8259431
TI  - Prediction of gallstone composition: synthesis of CT and radiographic features in
      vitro.
AB  - PURPOSE: To test a morphoradiographic algorithm designed to predict the
      composition of gallstones with use of computed tomography (CT) to define
      calcification patterns. MATERIALS AND METHODS: Two reviewers retrospectively
      evaluated the radiographic features of 120 separate in vitro specimens (59
      radiopaque and 61 radiolucent), then classified the stones into several
      categories of composition with the algorithm. RESULTS: The most useful features
      for prediction of cholesterol composition were, in order of decreasing
      importance, stone shape, absence of dense calcification on plain radiographs,
      overall CT attenuation not higher than that of water, presence of a second
      generation of smaller stones, and a peripheral cover of calcification detected on
      CT scans of aging cholesterol stones. The greatest error occurred in distinction
      between stones with mixed composition (50%-79% cholesterol) and older stones with
      higher cholesterol content (80%-95% cholesterol). CONCLUSION: The range of
      qualitative CT appearances advances the possibility of predicting gallstone
      composition and potential outcome of nonsurgical treatment.

PMID- 8259432
TI  - Performance testing of transrectal US scanners.
AB  - PURPOSE: To test the performance of transrectal ultrasound (US) scanners in the
      detection of low-contrast focal lesions as a function of depth, size, and
      contrast. MATERIALS AND METHODS: US images of two phantoms were analyzed by three
      observers. One phantom was most suitable for US units allowing scanning in the
      transverse or longitudinal planes, while the other was suitable for any scanning
      situation. Both phantoms were made of tissue-mimicking material and had six
      sections. Five sections contained different sizes of low-contrast simulated
      lesions, which were of different echogenicities and were randomly distributed to
      a depth of 8 cm. The sixth section contained only background material and served
      as a reference. A resolution zone, corresponding to the depth range over which a
      given type of lesion was detectable, was determined for each of the five lesion
      containing sections and a figure of merit equal to a weighted sum of resolution
      zone lengths computed. RESULTS: Data from 12 different scanner configurations
      were analyzed; a broad range of figures of merit were found. Agreement was found
      among the three observers regarding relative performance of the scanner
      configurations. CONCLUSION: The phantoms are useful for comparing performances of
      different transrectal US configurations.

PMID- 8259433
TI  - Condylar canal vein: unfamiliar normal structure as seen at CT and MR imaging.
AB  - PURPOSE: The vein of the posterior condylar canal is often seen (and occasionally
      misinterpreted) at computed tomography (CT) and magnetic resonance (MR) imaging.
      The CT appearance of the canal and the vein on a skull specimen was compared with
      the CT and MR appearance in patients. MATERIALS AND METHODS: One condylar canal
      of the skull specimen was marked with a wire that also indicated the course of
      the vein beneath the skull base. Axial and coronal CT images of the specimen were
      compared with CT or MR images of six patients, studied for various clinical
      indications, in whom the vein was apparent. RESULTS: In all six patients, the
      location of the vein beneath the skull base corresponded to the location
      predicted by the wire on the specimen. The normal vein may be prominent or
      diminutive. CONCLUSION: Recognition of the normal vein of the posterior condylar
      canal may prevent misinterpretation of the vein as a neoplasm or an abnormal
      lymph node at CT or MR imaging.

PMID- 8259435
TI  - Cortical organization in adulthood is modified by neonatal infarct: a case study.
AB  - PURPOSE: To assess anomalous cortical organization of somatosensory function in a
      23-year-old man who had had a neonatal infarct involving the left middle cerebral
      artery. MATERIALS AND METHODS: The infarct destroyed the primary and secondary
      somatosensory areas of the subject's left hemisphere but caused only mild
      perturbation of somatosensation on the right side of his body. With magnetic
      source imaging, the authors integrated magnetoencephalographic data with magnetic
      resonance imaging data to create magnetic source localization images that showed
      the mapping between brain function and structure. RESULTS: Electrical stimulation
      of the right median nerve evoked activity in two nontraditional areas: (a) an
      intact region of the left inferior temporal gyrus and (b) the ipsilateral right
      medial parietal cortex. CONCLUSION: These data suggest that bilateral neural
      reorganization can be induced by unilateral neonatal damage.

PMID- 8259434
TI  - Sensory motor cortex: correlation of presurgical mapping with functional MR
      imaging and invasive cortical mapping.
AB  - PURPOSE: To describe a clinically useful application of functional magnetic
      resonance (MR) imaging--presurgical mapping of the sensory motor cortex--and to
      validate the results with established physiologic techniques. MATERIALS AND
      METHODS: Functional MR mapping of the sensory motor cortex was performed in two
      women, aged 24 and 38 years. Both had intractable, simple partial motor seizures
      due to tumors located in or near the sensory motor cortex. They subsequently
      underwent invasive cortical mapping--direct cortical stimulation and/or sensory
      evoked-potential recording--to localize the affected sensory motor area prior to
      tumor resection. RESULTS: In both patients, the functional MR study demonstrated
      task activation of the sensory motor cortex. In both cases, results of cortical
      functional mapping with invasive techniques matched those obtained with
      functional MR imaging. CONCLUSION: Presurgical mapping of the sensory motor
      cortex is a potentially useful clinical application of functional MR imaging.

PMID- 8259436
TI  - Carotid and vertebral artery dissections: three-dimensional time-of-flight MR
      angiography and MR imaging versus conventional angiography.
AB  - PURPOSE: To compare three-dimensional time-of-flight magnetic resonance (MR)
      angiography, MR imaging, and transfemoral four-vessel angiography in diagnosis
      and follow-up of cervical artery dissection. MATERIALS AND METHODS: Eighteen
      patients with 19 extracranial internal carotid artery and five vertebral artery
      dissections were included in this prospective study. Blind interpretation of MR
      and angiographic images was made by two independent radiologists. RESULTS: MR
      angiography was more accurate than MR imaging in diagnosis of carotid dissection,
      although the difference was not statistically significant. In carotid artery
      dissection, respective sensitivity and specificity were 95% and 99% for MR
      angiography and 84% and 99% for MR imaging and in vertebral artery dissection
      were 20% and 100% for MR angiography and 60% and 98% for MR imaging. CONCLUSION:
      MR angiography is a reliable, noninvasive method for use in diagnosis and follow
      up of extracranial internal carotid artery dissection. In vertebral artery
      dissection, however, conventional angiography remains useful.

PMID- 8259437
TI  - Dose-response nonlinearities for benzene revisited: a reply to Crump et al.

PMID- 8259438
TI  - A response to OMB's comments regarding OSHA's approach to risk assessment in
      support of OSHA's final rule on cadmium.

PMID- 8259439
TI  - The health impact of major nuclear accidents: the case of Greece.
AB  - An assessment of the radiological consequences that would result for the
      population of Greece from postulated major nuclear accidents in the Kozloduy
      nuclear power station in Bulgaria is performed. Kozloduy lies at a distance of
      225 km from the northern borders of Greece and contains six reactors, all of the
      Russian WWER type. The postulated accidents that are classified as level 7
      accidents on the International Nuclear Event Scale, involve significant releases
      of radioactive materials into the environment, and widespread health and
      environmental effects. The analysis is performed by the MACCS code. The estimated
      consequences are compared to the corresponding actual impact of the Chernobyl
      accident in Greece. The results of the analysis indicate that, under the
      conservative assumptions adopted, the radiological consequences of the most
      severe accidents considered would be about 1.5 orders of magnitude larger than
      the actual radiological consequences of the Chernobyl accident.

PMID- 8259440
TI  - Environmental hazards in the Chinese public's eyes.
AB  - The People's Republic of China suffers each year from various environmental
      hazards. Although risk perception study has a 40-year history in Europe and North
      America, little is known about risk perception in China. Previous studies of risk
      perception have primarily focused on unnatural hazards, but China has experienced
      many natural environmental hazards. Therefore, the Chinese public's perceptions
      of environmental hazard risks must be considered in order to support the IDNDR
      program. The Chinese public's perceptions of environmental hazards are similar to
      those of Europeans and North Americans, but different characteristics are
      observed.

PMID- 8259441
TI  - Predicted infant exposure to tetrachloroethene in human breastmilk.
AB  - Based on a variety of maternal occupational and residential inhalation exposure
      scenarios, estimates of infant exposure to the dry-cleaning solvent
      tetrachlorothylene (perchloroethylene, PCE) in breastmilk were made.
      Physiologically based pharmacokinetic (PBPK) modeling indicates that infants may
      be exposed to elevated levels of PCE in breastmilk due to their mothers'
      inhalation of PCE. The PBPK-predicted breastmilk PCE concentrations agree very
      well with measured concentrations, where available. Based on this analysis,
      infants may be exposed to this workplace chemical via breastmilk at doses
      corresponding to rather high levels of risk. Predicted breastmilk doses provide
      the infant with little margin of exposure to doses associated with adverse health
      effects. In addition, the estimated increased cancer risks associated with these
      infant exposures are large under certain exposure scenarios. The actual
      concentrations of PCE in breastmilk of exposed mothers can only be known with
      certainty if monitoring is conducted. Due to the widespread exposure potential,
      monitoring studies should be undertaken so that the appropriate risk management
      alternatives can be better evaluated.

PMID- 8259442
TI  - Modeling long-term exposure of the whole population to chemicals in food.
AB  - This paper discusses a statistical exposure model (STEM) that can be used to
      estimate the percentage of the population exceeding ingestion intake criteria
      (e.g., ADI or TDI). In addition, STEM may be linked to toxicokinetic models to
      evaluate the interindividual variability in internal doses that results from
      variability in consumption habits. The assumptions of STEM are investigated by
      analyzing dioxin and cadmium intake data for the Dutch population.

PMID- 8259443
TI  - A physiologically based model for gastrointestinal absorption and excretion of
      chemicals carried by lipids.
AB  - Pharmacokinetic models which incorporate independently measured anatomical
      characteristics and physiological flows have been widely used to predict the
      pharmacokinetic behavior of drugs, anesthetics, and other chemicals. Models
      appearing in the literature have included as many as 18, or as few as 5 tissue
      compartments. With the exception of the multiple-compartment delay trains used by
      Bischoff to model the delays inherent to the appearance of drug metabolites in
      bile and segments of the intestinal lumen, very little effort has been made to
      incorporate the available information on gastrointestinal anatomy and physiology
      into more accurate gastrointestinal absorption/enterohepatic recirculation
      submodels. Since several authors have shown that the lymphatic system is the most
      significant route of absorption for highly lipophilic chemicals, we have
      constructed a model of gastrointestinal absorption that emphasizes chylomicron
      production and transport as the most significant route of absorption for
      nonvolatile, lipophilic chemicals. The absorption and distribution of
      hexachlorobenzene after intravenous vs. oral dosing are used to demonstrate
      features of this model.

PMID- 8259444
TI  - Risk assessment of virus in drinking water.
AB  - The reevaluation of drinking water treatment practices in a desire to minimize
      the formation of disinfection byproducts while assuring minimum levels of public
      health protection against infectious organisms has caused it to become necessary
      to consider the problem of estimation of risks posed from exposure to low levels
      of microorganisms, such as virus or protozoans, found in treated drinking water.
      This paper outlines a methodology based on risk assessment principles to approach
      the problem. The methodology is validated by comparison with results obtained in
      a prospective epidemiological study. It is feasible to produce both point and
      interval estimates of infection, illness and perhaps mortality by this
      methodology. Areas of uncertainty which require future data are indicated.

PMID- 8259445
TI  - Dimensions of risk perception for financial and health risks.
AB  - This study of 29 MBA students compares two models of risk perception for both
      financial and health risk stimuli. The first, inspired by Luce and Weber's
      Conjoint Expected Risk (CER) model, uses five dimensions: probability of gain,
      loss and status quo, and expected benefit and harm. The second, inspired by the
      Slovic et al. psychometric model, employs seven dimensions: voluntariness, dread,
      control, knowledge, catastrophic potential, novelty, and equity. The CER-type
      model provided a better fit for most subjects and stimuli. Adding the
      psychological risk dimensions from the Slovic et al. model explained only
      modestly more variance. Relationships between the dimensions of the two models
      are described and the construction of a hybrid model explored.

PMID- 8259446
TI  - A malformation incidence dose-response model incorporating fetal weight and/or
      litter size as covariates.
AB  - A dose-response model is often fit to bioassay data to provide a mathematical
      relationship between the incidence of a developmental malformation and dose of a
      toxicant. To utilize the interrelations among the fetal weight, incidence of
      malformation and number of the live fetuses, a conditional Gaussian regression
      chain model is proposed to model the dose-response function for developmental
      malformation incidence using the litter size and/or the fetal weight as
      covariates. The litter size is modeled as a function of dose, the fetal weight is
      modeled as a function of dose conditional on both the litter size and the fetal
      weight, which itself is also conditional on the litter size, and the malformation
      incidence is modeled as a function of dose conditional on the litter size. Data
      from a developmental experiment conducted at the National Center for
      Toxicological Research to investigate the growth stunting and increased incidence
      of cleft palate induced by Dexamethasone (DEX) exposure in rats was used as an
      illustration.

PMID- 8259447
TI  - Effects of the mechanism of receptor-mediated gene expression on the shape of the
      dose-response curve.
AB  - A mathematical model of receptor-mediated gene expression that includes receptor
      binding of natural and xenobiotic ligands, protein synthesis and degradation, and
      metabolism of the xenobiotic ligand was created to identify the determinants of
      the shape of the dose-response profile. Values of the model's parameters were
      varied to reflect alternative mechanisms of expression of the protein. These
      assumptions had dramatic effects on the computed response to a bolus dose of the
      xenobiotic ligand. If all processes in the model exhibit hyperbolic kinetics, the
      dose-response curves can appear sigmoidal but actually be linear with a positive
      slope at low doses. The slope of the curve only approached zero at low dose,
      indicative of a threshold for response, if binding of the xenobiotic ligand to
      the receptor exhibited positive cooperativity (ligand binding at one site
      increases the affinity for ligand at another binding site on the receptor).
      Positive cooperativity in the rate-limiting step of protein synthesis produced
      dose-response curves which were "U-shaped" at low doses, also indicative of a
      threshold. Positive cooperativity in the metabolism of the xenobiotic ligand
      produced dose-response curves that increased more rapidly than linearly with
      increasing dose. The model illustrates the fact that response cannot be predicted
      from qualitative mechanistic arguments alone; any assessment of risk to health
      from xenobiotic chemicals must be based on a detailed quantitative examination of
      the kinetic behavior of each chemical species individually.

PMID- 8259448
TI  - [Lyme borreliosis: clinical and diagnostic aspects].

PMID- 8259449
TI  - [Diagnostic and therapeutic thoracoscopy: apropos of 100 cases].
AB  - Results and complications of 100 consecutive thoracoscopies performed with local
      anesthesia, in our department of pneumology are reviewed. The group is
      constituted by 60 men and 40 women with an average age of 56.1 +/- 16.7 years (13
      81). Age difference between tumoral (n = 58) and tuberculous patients (n = 13)
      was statistically significant (59.6 +/- 12.8 vs 39.3 +/- 18.7; p < 0.001). The
      most frequent symptom on presentation was dyspnea, an significant association was
      detected between fever and tuberculosis (p < 0.001). Final diagnosis were: tumor
      (n = 58), non-specific inflammation (n = 16), tuberculosis (n = 13), pneumothorax
      (n = 11) and pneumonia (n = 2). In 14 patients some complication of the procedure
      appeared, all of these had little clinical significance and were resolved with
      minimal nursing care. To diagnose tumor, macroscopic aspect showed a sensitivity
      of 96.1%, specificity of 86% and 92% assurance.

PMID- 8259450
TI  - [Pharmaceutical marketers: professional and informative aspects].
AB  - This study tries to know the opinion of pharmaceutical detailers about their
      profession, as well as their pharmacological knowledge. 75 questionnaires were
      distributed to an equal number of detailers. The questionnaires were composed of
      two parts. In the first one, several questions about their profession were posed.
      In the second one, the questions were about Pharmacology. The main results were
      that most of them have got only lower degrees; however, they all have carried out
      training courses in their companies. With regard to pharmacological questions,
      percentage of success was 61%.

PMID- 8259451
TI  - [Cardiac tamponade as a presentation of primary hypothyroidism in a young woman].
AB  - Pericardial effusion (PE) as a hypothyroidism associated sign, is something that
      can be found with relative frequency; nevertheless, cardiac tamponade (CT) as the
      first sign of this disease may be considered exceptional especially in young
      patients. We report a 31 years old woman with clinical symptoms and signs of CT
      that in the forward workshop was diagnosed of primary hypothyroidism as cause of
      the CT. We shortly describe the case and review the literature, emphasizing the
      importance of the knowledge of CT trigger factors in myxedematous PE, as well as
      its usual benign evolution with hormonal treatment, without recurrences of the CT
      after pericardiocentesis is performed. This justify a conservative approach, in
      spite of the slow resolution of the PE what can take as long as 1.5 years.

PMID- 8259452
TI  - [Hypophosphatemic osteomalacia secondary to a vascular fibrous histiocytoma].
AB  - Management of an adult woman with a 3 years untractable low back pain, allowed us
      to discover the existence of hypophosphatemic osteomalacia, due to a benign
      mesenchymal tumor (vascular fibrous histiocytoma). The prognosis of this form of
      osteomalacia, as in the present case, is excellent after total removal of the
      tumor.

PMID- 8259453
TI  - [Transient motor aphasia at high altitude].
AB  - Three healthy mountaineers had episodes of transient motor aphasia at 5,547,
      8,000 and 7,000 metres respectively. In the three cases the comprehension was
      preserved. Aphasia was neither accompanied nor followed by headache, motor
      disturbances or any other neurologic symptoms and signs. We suspect that
      transient motor aphasia is more frequent at high altitude than can be concluded
      from its low frequency of apparition in the medical literature. Among the
      pathogenic hypotheses, we consider the disfunction of language-related brain
      areas due to vascular obstruction by microthrombi of platelets and fibrin or to
      selective hypocapnic-mediated vasoconstriction, but a diffuse metabolic illness
      cannot be ruled out.

PMID- 8259454
TI  - [Generalized lymphadenopathy with morphologic findings of multicentric
      angiofollicular ganglionic hyperplasia in a patient with AIDS].
AB  - We report a case of a 33-year-old man, intravenous drugs abuser, HIV-positive,
      with peripheral lymphadenopathy, hepato-splenomegaly and fever, in which a
      ganglionic biopsy showed a histology with morphologic features of multicentric
      Castleman's-like disease, and minute foci of Kaposi's sarcoma ganglion, without
      cutaneous lesions. Given the interrelationships between this morphology of
      angiofollicular lymph node hyperplasia, the development of Kaposi's Sarcoma, and
      the aggressive clinical course seen in our patient and those in the literature,
      the use of lymph node biopsy may be an important prognostic tool for the patients
      with the acquired immunodeficiency syndrome.

PMID- 8259455
TI  - [Cutaneous melanoma: a review of risk factors].
AB  - In Europe, mortality due to cutaneous malignant melanoma represents 5,000 deaths
      a year, during this period about 17,000 people develop this disease. The highest
      incidence rates are those of Northern Europe, where this neoplasm has always been
      a public health problem, nevertheless countries of southern Europe (Spain,
      Portugal, Greece, Italy ...) are showing important increments in their rates,
      during the last years. Because of all of this, it is becoming a public health
      problem in every white race populations. This increment in its incidence is
      mainly attributed to changes in lifestyle, with an increase of solar radiation
      exposure during holidays and leisure activities, increase of tobacco and alcohol
      consumption, exposure to different chemical substances, use of ultraviolet lamps,
      etc.

PMID- 8259456
TI  - [Clonal myelodysplasia: prognostic stratification and therapeutic possibilities].
AB  - Myelodysplastic syndromes represent an entire group of clonal panmyelopathies
      with very distinct evolutionary pathways. Their common denominator, however, is a
      self-maintained functional failure of the myeloid hemopoiesis which tends to
      evolve into severe non-lymphoid leukemia (SNLL) in 20-30% of the cases. First,
      the prognostic value of each the following is reviewed: the morphological
      classification F.A.B., the stratification system for "Bournemouth group", the
      abnormal placement of immature myeloid precursors (ALIP) in bone marrow, and
      cytogenetic changes. Second, the therapeutic potential for each of the following
      is assessed: vitamin and support treatments; suprarenal steroids; conventional
      androgens and danazol; agents of cellular differentiation (cytosine arabinoside
      in low doses, retinoid acids, vitamin D3, etc.). Finally, the role of aggressive
      chemotherapies (in succession or unrelated to marrow transplant) in the
      eradication of myelodysplastic clone or post-myelodysplasia SNLL is examined.

PMID- 8259457
TI  - [Magnesium. New perspectives].
AB  - We reviewed the literature on the Mg++ cation with special attention on the
      clinico-therapeutical, physiopathogenic, and biochemical aspects. We extended the
      survey to some pathologies such as cardiovascular diseases and diabetes mellitus,
      given our understanding that a deficiency of this ion may constitute a primary
      cardiovascular risk factor. The dissociation present between the levels of
      intracellular and serum Mg++ is shown, since it may invalidate results that
      follow. We place special emphasis on the necessity to treat certain pathologies
      with magnesium salts and to quantify, with successive studies, the amount to
      administer.

PMID- 8259458
TI  - [Therapeutic approaches to cryptosporidiosis. A review of the literature].
AB  - Cryptosporidiosis is a coccidian infection that usually occurs in children an
      immunocompromised patients. With the AIDS (Acquired Immunodeficiency Syndrome)
      epidemic there have been an increased number of clinical cases and still we don't
      have an optimal therapeutic regimen to eradicate the infection. Since 1907 when
      the organism was first described, a large amount of anti-infective agents have
      been used without success. We present herein a review of the new therapeutic
      approaches, although none of them is satisfactory and new studies are required
      for the development of an optimal treatment. Symptomatic and nutritional support
      are the unique treatment we have so far.

PMID- 8259459
TI  - [Thoracic mass and peripheral ischemic events].

PMID- 8259460
TI  - [Young man with pain in the left hemithorax].

PMID- 8259461
TI  - [Acute febrile syndrome, meningeal syndrome and changes in behavior in a 26 year
      old heroin addict].

PMID- 8259462
TI  - [Acute multifocal bacterial nephritis in a patient without risk factors].

PMID- 8259463
TI  - [Nephrotic syndrome secondary to d-penicillamine in a patient with Wilson's
      disease].

PMID- 8259464
TI  - [Changes in route of drug administration in heroin addicts].

PMID- 8259465
TI  - [Pulmonary granulomatosis due to talc].

PMID- 8259466
TI  - [Community acquired Escherichia coli pneumonia in a patient with an asymptomatic
      colon adenocarcinoma].

PMID- 8259467
TI  - [Spinal syndromes. On the clinical aspects and possibilities of conservative
      therapeutic approaches].
AB  - The great socio-economic importance of back pain is undisputed. A precise
      definition and nomenclature of the multiple clinical syndromes aids in a clearer
      assessment of the individual problems of the patient and subsequently the
      selection of suitable conservative therapeutical measures. It is stressed that
      each treatment has to be selected with care and in consideration of the
      individual situation. The lack of generally applicable recommendations and
      patented recipes is emphasized. Therapeutical possibilities are essentially based
      on three columns: active and passive physical treatment both supported by the
      third mean, pharmacotherapy. Secondary prophylaxis following the acute phase of
      the disease should not be forgotten.

PMID- 8259468
TI  - [Psychophysiologic manifestations, psychological and somatic risk factors and the
      physician-patient relationship in patients with heart diseases].
AB  - In daily medicine we often see patients complaining about thoracic pain. There is
      little doubt about the etiology in the most cases, but several patients continue
      posing diagnostic problems. There are different pathophysiological views to
      understand the situation of those patients, and it is important to determine
      their mental and psychological conditions. For this purpose, the focus on
      transference and countertransference phenomena has to be stressed. With these
      elements it will be possible to determine the diagnostic and therapeutic approach
      to those patients to reassure them and to justify investigations.

PMID- 8259469
TI  - [Restless legs syndrome. Report of experience].
AB  - Clinical presentation and therapy of the Restless-Leg-Syndrome are featured using
      the report of the author's own case. Although this is a harmless disease, it can
      considerably reduce the quality of life. The syndrome is not rare (1 to 5% of
      prevalence). Effective therapeutic means have only been known for a few years. In
      the presented report, an alternating therapy with L-Dopa and Codeine, given in a
      rhythm of 2 months, produced very good results. No addiction to the drugs, and in
      particular no need of a dosage increase was observed during the whole period of
      18 months.

PMID- 8259470
TI  - [Liver transplantation. Facts and trends].
AB  - The aim of this article is to orientate the non-specialist in the field of liver
      transplantation. The main indications and contraindications are reviewed. The
      surgical technique is briefly illustrated and the postoperative follow-up is
      described. Several points have been raised on the present and future trends of
      this technology which may give the reader some food for thought. The authors
      state that liver transplantation is too infrequently performed in Switzerland.
      Some candidates for the operation are not identified, whilst others are referred
      too late to a transplantation center.

PMID- 8259471
TI  - [Development of dementia].
AB  - A 67-year old male patient was admitted to our clinic because of slowly
      developing dementia. Severe dysfunction of memory, confusional states and urinary
      incontinence were observed. A diagnosis of general paresis was made by positive
      serology for syphilis and CSF examination. The patient's condition improved
      markedly after high-dose penicillin G treatment.

PMID- 8259472
TI  - [Case from general practice (280). Cluster headache].

PMID- 8259473
TI  - [The HIV test in the hospital and general practice--discussion of expanded use of
      the voluntary HIV test. Symposium 17 June 1993 in the Luzern canton hospital].

PMID- 8259474
TI  - [Alcoholic ketoacidosis].
AB  - Alcoholic ketoacidosis (AKA) is an important and probably underdiagnosed
      differential diagnosis for metabolic acidosis with an increased anion gap. It
      occurs in patients with prolonged ethanol intake. After a brief period of
      starvation induced by alcoholic gastritis patients typically present with
      vomiting, abdominal pain and Kussmaul breathing. Routine testing for urine or
      serum ketones with ketostix may be negative, since they do not detect beta
      hydroxybutyrate and this is characteristically elevated in AKA. We present three
      cases of AKA and discuss diagnosis, pathophysiology and management of this
      disorder.

PMID- 8259475
TI  - [Effect of ciprofloxacin therapy in duration of bacterial excretion in acute
      salmonella gastroenteritis].
AB  - In view of the increasing incidence of non-typhoid salmonellosis, the effect of
      early treatment with ciprofloxacin on the permanent elimination of salmonella was
      evaluated. In a prospective study, 14 patients with non-typhoid salmonellosis
      were treated with 2 x 500 mg/d ciprofloxacin for 10 days within 5 days of onset
      of symptoms. Relapse occurred in 4/14 (29%) patients 2-3 weeks after termination
      of therapy. Using sero- and ribotyping, relapse was confirmed and reinfection
      ruled out in 4/4 patients. Furthermore, ribotyping suggested double infection in
      one patient. Development of resistance to ciprofloxacin was not observed. We
      conclude that the use of antimicrobial chemotherapy to treat non-institutional
      salmonellosis in immunocompetent patients cannot generally be recommended but
      must be considered carefully in each case. Indications for ciprofloxacin therapy
      in the treatment of non-typhoid salmonellosis are discussed.

PMID- 8259476
TI  - [Trichomegaly in HIV infection].
AB  - Hypertrichosis of the eyelashes was first described as "trichomegaly" in the
      setting of rare congenital syndromes. Recently numerous cases of acquired
      trichomegaly of the eyelashes have been described, especially in patients with
      advanced human immunodeficiency virus type I infection. The pathomechanisms
      leading to acquired trichomegaly remain largely unknown. Direct effects of the
      virus on the hair follicle, immune dysregulation, and a multifactorial
      pathogenesis are discussed. We report a case of acquired trichomegaly in advanced
      HIV-I infection in order to present this unusual clinical finding and other hair
      problems in AIDS patients. It is suggested that acquired trichomegaly of the
      eyelashes may act as a useful clinical marker for assessment of severity of HIV-I
      infection.

PMID- 8259477
TI  - [Thrombosis of the right auricle in pulmonary embolism: value of echocardiography
      and indications for thrombolysis].
AB  - The presence of a right atrial thrombus is a recognized predictive factor of high
      mortality in patients with pulmonary embolism. In this report we describe two
      cases in which a free-floating thrombus in the right atrium was demonstrated by
      echocardiography; it resolved rapidly in both cases after thrombolytic therapy
      which resulted in a rapid clinical improvement and favorable outcome. During the
      acute phase of pulmonary embolism, a dilated right ventricle, a dilated pulmonary
      artery, a left ventricle of small size and paradoxical motion of the
      interventricular septum can be detected by echocardiography. In cases of massive
      pulmonary embolism or when there is doubt regarding the diagnosis, this
      noninvasive method serves to guide diagnostic and therapeutic decisions. In the
      special case where a right atrial thrombus is detected by echocardiography,
      thrombolytic therapy seems warranted.

PMID- 8259478
TI  - [Infection of the shoulder joint. Etiology, diagnosis and therapy].
AB  - Acute infections of the shoulder joint have to be considered as an emergency and
      must be treated immediately. The significance of an infected glenohumeral joint
      is demonstrated by the functional results, which are poorer than other in joint
      infections. Irreversible cartilage damage is already observable after one week,
      and impairment of motion resulting in invalidity may result. Early functional
      physiotherapy is necessary to avoid shoulder ankylosis. The etiology,
      characteristic clinical findings, radiologic examinations and different forms of
      therapy are summarized. By early diagnosis, with immediate and adequate therapy,
      it is possible to avoid devastating results.

PMID- 8259479
TI  - ["Functional" disorders--from the viewpoint of the neurologist].
AB  - Patients with "functional" neurological diseases, i.e. suffering from nonorganic
      pseudo-neurological disorders, are common in neurological practice and account
      for a significant minority of neurological admissions. The nomenclature of these
      disorders is confusing and there is still no satisfactory system of
      classification. Many of these patients are misdiagnosed. The diagnostic problems
      and treatment of these disorders are illustrated by 4 case reports.
      Pathophysiologically the disorders are ill understood. Many of their bizarre
      features may serve as a means of nonverbal communication for these patients.
      Their management requires close collaboration between neurologists and
      psychiatrists. Behavioural therapy may be a more appropriate treatment for these
      disorders than classical analytic psychotherapy.

PMID- 8259480
TI  - [Initial experience with surgical uro-laparoscopy].
AB  - Preliminary experience with uro-laparoscopy was retrospectively analyzed to
      determine whether patients profited from the laparoscopic procedure. Between
      August 1991 und July 1993 we performed 53 operations laparoscopically. Four more
      began in this way but ended in open surgery. 29 varicocele procedures were
      carried out. A reduced postoperative morbidity, and hence a benefit, were obvious
      in 3/29 patients with bilateral varicocele, but probably not in the remaining
      26/29 patients affected only on the left side. 13 pelvic lymphadenectomies in
      patients with prostatic carcinoma T1-3, elevated prostatic acid phosphatase, a
      PSA > 30 ng/ml and/or a suspected N+ on CT, served to identify 10 pN0 and 3 pN1
      patients. Four of the pN0 patients with a T3 tumor were given radiotherapy. Six
      with a T2 tumor underwent radical prostatectomy, four with margin-negative
      specimens benefited from laparoscopic lymphadenectomy by securing a curative
      operation which according to established rules would otherwise have been
      withheld. Two patients with margin-positive specimens suffered harm from
      laparoscopic lymphadenectomy, which had led to a needless operation. Another
      lymphadenectomy performed on one more patient suffering from deep venous
      thrombosis of the left leg associated with pelvic lymphadenopathy established the
      benign histology of the enlarged lymph nodes with minimal morbidity. 10
      nephrectomies were carried out for benign, clinically relevant lesions of the
      kidney, which are rare. They produced a clear-cut benefit for all patients as the
      postoperative morbidity was minimal. We conclude that the present indications for
      uro-laparoscopic procedures are either disputable or rare.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8259481
TI  - [Lumbar puncture--the post-puncture syndrome. Prevention with an "atraumatic"
      puncture needle, clinical observations].
AB  - Postlumbar puncture syndrome (PPS) is caused by continuous leakage of CSF through
      the dural puncture defect. While it has long been known that the symptoms are
      dependent on the diameter of the puncture needle, the influence of the needle
      point on the frequency of PPS has now also been examined. Following diagnostic
      and/or therapeutic lumbar puncture (LP) with Sprotte's "atraumatic" needle, the
      symptoms in 600 patients during a period of 8 days were recorded. In 92% of the
      patients LP involved no problems. In 7% the puncture was successful only at the
      second or third attempt. In 4 cases it was necessary to carry out the procedure
      under X-ray control. While the literature shows that PPS following lumbar
      puncture with a 21 G needle occurs in 30-40% of cases, only 3.6% of the patients
      complained about position-dependent headaches where the Sprotte needle was used.
      Nausea, dizziness and tinnitus were extremely rare (< 1%).--The "atraumatic"
      puncture needle reduces the frequency and the degree of PPS to the minimum and
      makes the lumbar puncture procedure possible on an outpatient basis.

PMID- 8259482
TI  - [Hepatosplenic schistosomiasis: case report and clinical review].
AB  - Although seen rarely in Switzerland, schistosomiasis is a parasitosis affecting
      200 to 250 million people round the world, mainly in tropical and subtropical
      regions of Africa, Asia, Central and South America. Depending on the parasitic
      species, the ureters and the bladder (S. haematobium) or the intestine and the
      liver (S. mansoni, S. japonicum, S. mekongi) are primarily involved. Other organs
      may be affected (lung, kidneys and central nervous system). Hepatosplenic
      schistosomiasis represents a special form of chronic infection by S. mansoni, S.
      japonicum or S. mekongi predominantly occurring in adolescents heavily and
      repeatedly infected during childhood, together with an additional genetic
      predisposition for the disease. Hepatosplenic schistosomiasis on a worldwide
      scale is one of the most prevalent causes of portal hypertension in man. We
      describe a 33-year-old Portuguese female with mansonian hepatosplenic
      schistosomiasis 12 years after leaving Africa, who had hepatosplenomegaly, portal
      hypertension, esophageal varices and hypersplenism. Splenomegaly and slight
      anemia had been known for years without prompting further work-up. Two months
      before diagnosis she had been delivered of a normal child after pregnancy without
      portal-hypertensive complications, namely esophageal hemorrhage. Because of
      placenta accreta, however, erythrocyte transfusion had been performed after
      delivery and was possibly responsible for hepatitis C found later on.
      Pathophysiology, clinical findings and therapy of the disease are discussed.

PMID- 8259483
TI  - [Inflammatory myopathy: unusual presentation of a case of Wegener disease].
AB  - The case is presented of a 66-year-old man who developed an inflammatory myopathy
      picture predominantly consisting in leg weakness. Wegener's granulomatosis was
      diagnosed on the basis of suggestive thoracic imaging, microhematuria and
      necrotizing arteritis with granulomas in muscular biopsy. An increasing titer of
      anti-neutrophilic cytoplasm auto-antibodies (ANCA) confirmed the diagnosis. Rapid
      resolution was obtained by classic immunosuppressor treatment (cyclophosphamide
      and corticoids), without worsening of renal function. In discussion we emphasize
      the importance of ANCA measurement for diagnosis and follow-up.

PMID- 8259485
TI  - The relationship between mercury concentration in human organs and different
      predictor variables.
AB  - Samples from different tissues were collected from autopsies of individuals of
      the general population of the Stockholm area, Sweden. The samples were analysed
      for total mercury content using radiochemical neutron activation analysis.
      Average concentrations of mercury in occipital cortex, abdominal muscle,
      pituitary gland and kidney cortex were, 10.6 (2.4-28.7), 3.3 (0.9-5.4), 25.0 (6.3
      77) and 229 (21.1-810) micrograms/kg wet weight, respectively. Possible predictor
      variables for mercury concentrations were tested in multiple linear regression
      models. An effect of a number of tooth surfaces with amalgam was seen in
      occipital lobe cortex, abdominal muscle and pituitary gland, but not in kidney
      cortex. In occipital lobe cortex and abdominal muscle, concentrations of mercury
      increased with age. Explanations discussed include: that a significant fraction
      of the mercury retained from amalgam fillings has a very long biological half
      life; a decreasing capacity of mercury excretion with age; or higher fish
      consumption in the older individuals. In kidney cortex mercury concentrations
      decreased with age. The reason for this remains unclear, but it might indicate a
      decreasing capacity of mercury excretion with age. Chronic alcohol abuse was
      associated with decreased concentrations of mercury in occipital cortex.

PMID- 8259484
TI  - Concentrations and sources of cadmium, copper, lead and zinc in house dust in
      Christchurch, New Zealand.
AB  - The amounts (microgram m-2) and concentrations (microgram g-1) of cadmium,
      copper, lead and zinc have been measured in house dust in Christchurch, New
      Zealand. For 120 houses surveyed the geometric mean concentrations of the four
      metals are 4.24 micrograms g-1, 165 micrograms g-1, 573 micrograms g-1 and 10,400
      micrograms g-1, respectively. In addition eleven variables, such as house age,
      carpet wear and traffic density, were recorded for each property and the results
      analysed with respect to their effects on the amounts and concentrations of the
      four elements. The amounts of all the metals were highly correlated with the
      overall dustiness of the houses, which was found to be predominantly determined
      by the degree of carpet wear. No one dominant source of cadmium was identified,
      although several minor sources including carpet wear, galvanized iron roofs and
      red/orange/yellow coloured carpets were implicated. Petrol lead and lead-based
      paints were identified as significant sources of lead in house dust. Rubber
      carpet underlays or backings were identified as a significant source of zinc,
      with some contribution from galvanized iron roofs. Road traffic and probably the
      existence of a fire place appear to contribute to the copper levels.

PMID- 8259486
TI  - Impact of organochlorine pesticide residues and PCBs on otters (Lutra lutra): a
      study from western Britain.
AB  - A study of otter (Lutra lutra) populations and levels of organochlorine (OC)
      pesticide residues and PCBs in otter droppings (spraints) was made on eight
      stretches of river in three catchments in Wales and West Midland England.
      Population and contaminant levels were compared against target values. The otter
      populations (as measured by an index) remained stable on one stretch over 11
      years, while they increased rapidly to equilibrium on four other stretches. The
      three lower stretches of rivers showed more erratic trends and on only one
      stretch did the index exceed, occasionally, the target value. Marking intensity
      at spraint sites was also lower at the three lowland sites. Concentrations of
      dieldrin, DDE and PCBs were significantly greater in spraint samples from the
      three lowland stretches. Over 50% of samples from the three lowland stretches had
      OC concentrations above the maximum allowable concentration, whereas most samples
      from the upland stretches had concentrations below the 'no effects level'. It is
      suggested that the colonization, by otters, of their former lowland range is
      inhibited by OC contamination of their food chain but, if contaminant levels can
      be reduced, spread will occur rapidly.

PMID- 8259487
TI  - Impact of organochlorine pesticide residues and PCBs on otters (Lutra lutra) in
      eastern England.
AB  - A study of otter (Lutra lutra) populations and levels of organochlorine (OC)
      pesticide residues and PCBs in otter faeces (spraints) was made on rivers in East
      Anglia, England. Population and contaminant levels are compared against target
      values. It is thought that the native otter population was almost extirpated
      during the study period. The current population must derive largely, if not
      entirely, from captive-bred animals introduced since 1983. Its range has expanded
      little and population levels, measured as an index, were generally low.
      Concentrations of OC pesticides and PCBs were similar to those of lowland
      stretches of western rivers; however, samples had a smaller proportion of
      dieldrin and a greater proportion of PCBs. Overall 44% of samples had
      concentrations of contaminants exceeding the 'level of concern'. It is considered
      that contamination, especially by PCBs, remains a factor influencing otter
      populations, which may not be viable in East Anglia without repeated releases of
      captive-bred animals.

PMID- 8259488
TI  - Apportioning the sources of lead in house dusts in the London borough of
      Richmond, England.
AB  - The sources of particulate lead in houses in the London Borough of Richmond,
      England have been investigated using automated scanning electron microscopy in
      conjunction with energy dispersive X-ray spectroscopy. Compositional and size
      information was collected on lead-bearing particles from density and size
      fractionated floor dusts from 16 residences of various ages. A classification
      scheme based on the analysis of different types of lead source particles was used
      to categorize the house dust particles as either auto exhaust, road dust, garden
      soil, paint, high temperature process emissions, lead of common origin or
      miscellaneous lead-bearing. Classification results based on both populations of
      particles and estimated particle volumes suggest that paint, road dust and garden
      soil are the major contributors of particulate lead to the Richmond households.
      The primary contributing source in the 64-1000-microm size range of the house
      dusts appears to be paint. In the 0-64-microm size fraction of the dusts paint,
      road dust and garden soil all make significant contributions. Variations in the
      contributions made by the major sources appear to be unrelated to the age of the
      homes.

PMID- 8259489
TI  - Studies on the leaching of fluoride in tea infusions.
AB  - In order to assess the levels of fluoride ingestion through intake of tea,
      studies were conducted with four different brands of tea leaves commonly
      available in the Indian market. Four most prevalent methods for the preparation
      of tea with various contact times (2,4,6,8 and 10 min) of tea leaves with water
      show that: (a) leaching of fluoride is least in case of leaf tea as compared to
      powdered tea (F levels increasing with decreasing grain size); (b) leaching of
      fluoride reaches a maximum after a contact of about 6 min; (c) there is no
      difference between levels of fluoride with or without addition of milk in the
      English style where tea leaves are not boiled, while for the Indian style,
      addition of milk and subsequent boiling resulted in reduction of fluoride levels
      and (d) ingestion of fluoride per cup of tea ranged from 1.55 mg/l to 3.21 mg/l
      amounting to an intake per day per person of fluoride between 0.3 to 1.9 mg.

PMID- 8259490
TI  - Variability of blood lead levels in an urban population in relation to drinking
      and smoking habits.
AB  - The influence of drinking and smoking habits on blood lead levels of an urban
      population was assessed in this study. Lead concentrations were determined in 287
      blood samples collected from non-occupationally lead exposed men living in
      Barcelona, Spain. Blood lead levels significantly increased with the consumption
      of wine. Although not statistically significant, a similar tendency was also
      observed for beer drinkers, but not for the consumers of spirits. Slight
      increases in the blood lead concentrations of smokers were also found. However,
      because of the significant correlation between heavy smoking and drinking
      observed in this study, alcohol consumption would probably be responsible for
      these increases. Wine consumption was the most influential variable (7.72%, P <
      0.001) on the blood lead levels of the population examined.

PMID- 8259491
TI  - In vivo detection of waste water and industrial effluent genotoxicity: use of the
      Newt Micronucleus Test (Jaylet Test).
AB  - The genotoxic potential of various waste waters has been evaluated in a
      micronucleus test using amphibian larvae. Genotoxicity was detected after
      dilution, in waste water from tanneries and from various petrochemical
      industries. Further studies have shown that sample treatment used for in vitro
      testing may affect the genotoxic response. Sterilization by gamma irradiation
      lowered genotoxic activity. Furthermore, microfiltration of effluent and
      extraction of organic micropollutants on XAD-4 resins, lead to the preparation of
      extracts which are not fully representative of the initial water sample. Testing
      of concentrates, as required for in vitro studies, will limit the scope of a
      survey to that part of the organic matter that can be recovered by concentration
      techniques. Many of the problems encountered in in vitro genotoxicity studies of
      waters, may be circumvented with direct testing on aquatic organisms. Thus, there
      is no need to concentrate or sterilise a sample. The tests can be carried out
      with intact animals, thus taking into account uptake and elimination, internal
      transport and metabolism. Finally, in vivo test-systems, such as the Newt
      Micronucleus Test, are more relevant to eukaryotes than bacterial assays and are
      suitable to assess the real impact of genotoxins discharged in the aquatic
      environment.

PMID- 8259492
TI  - Concentration of selected metals in penguins and other representative fauna of
      the Antarctica.
AB  - Concentration of Zn, Cu, Cd, Pb, Ag, Co, Ni, Cr, Mn and Fe were determined in
      muscle and liver of three species of penguins and other animals of the antarctic
      region. Liver was characterized by maximum concentrations of all the metals
      analyzed. The element levels in the samples assayed are in keeping with those
      reported previously by other authors. It is assumed that specific food habits of
      penguins are mainly responsible for elevated Cd levels in livers of these birds.

PMID- 8259493
TI  - Prolonged low-level cadmium intake and atherosclerosis.
AB  - The frequencies of 10 diseases in a cadmium (and zinc) contaminated region in The
      Netherlands were analysed by comparing hospital admissions with those of a non
      contaminated region and with national values. No significant differences were
      found for diseases which are commonly associated with increased cadmium uptake
      such as renal insufficiency, nephrolithiasis, hypertension, cancer, immaturity of
      the new-born. For the contaminated region a significantly higher frequency was
      only found for atherosclerosis; this was relatively strong for men aged > 40 yrs.
      However, no higher death frequency for atherosclerosis was observed. The results
      are discussed in relation to limitations in the evaluation techniques used. The
      absence of major health risks in the contaminated area is obvious, but the
      possible influence of long term-low level cadmium uptake on atherosclerosis
      requires more attention.

PMID- 8259494
TI  - Lead-210 in vegetables and soils from an area of high natural radioactivity in
      Brazil.
AB  - Contamination of vegetables and associates soils by 210Pb, originating either by
      natural fallout from uranium or by the processing mills of Pocos de Caldas
      (CIPC), State of Minas Gerais, Brazil is estimated by comparison with similar
      control samples collected from areas distant from the mining and milling
      operations. For lichens and bryophytes, the mean values of 210Pb concentrations
      were significantly higher than those of the control region. Similarly, vegetables
      and soils from kitchen-gardens located near the mill contained much higher
      concentrations of 210Pb than those observed for other regions.

PMID- 8259495
TI  - Persistence and prediction of radiocaesium levels in animals grazing semi-natural
      environments.
AB  - In vivo monitoring of radiocaesium levels in a flock of mountain sheep grazing a
      heather-dominant peatland ecosystem was undertaken over a 3-year period from 1989
      to 1991. Highest values were observed during summer and autumn and measurable
      radiocaesium activities were present throughout the year. Comparably high mean
      and maximum values recorded in November 1989 are thought to be a result of fungi
      consumption. Analysis of variance indicated that an increase of 4% occurred in
      radiocaesium levels in muscle between 1989 and 1990 followed by an overall
      decrease of 35% between 1990 and 1991. In order to test an existing model to
      predict radiocaesium levels in muscle from measured activities in faeces, an
      independent data set was produced. The radiocaesium content of faecal samples
      collected from the grazing range of a sheep flock was compared with the results
      of in vivo measurements on the same animals. The correlation over time between
      the predicted and observed flock mean and maximum values was found to be
      significant, thereby confirming the value of faeces sampling as an inexpensive
      and rapid means of assessing the distribution of radiocaesium activities in sheep
      flocks grazing semi-natural ecosystems.

PMID- 8259496
TI  - Evolution of scientific research.

PMID- 8259497
TI  - Mind and brain.

PMID- 8259498
TI  - Scientific evidence and the courts.

PMID- 8259499
TI  - Scientific evidence and the courts.

PMID- 8259500
TI  - Health care and life expectancy.
AB  - The four pictures of the moon accompanying the review by Ursula B. Marvin of To a
      Rocky Moon: A Geologist's History of Lunar Exploration by Don E. Wilhelms (9
      July, p. 231) should have been in reverse order on the page.

PMID- 8259501
TI  - Endgame for MicroGeneSys vaccine trial?

PMID- 8259502
TI  - Psychiatry chair ousted amidst schism at UCSF.

PMID- 8259503
TI  - AIDS in Europe. German blood contamination found low.

PMID- 8259504
TI  - AIDS drug development. Task force to speed drug pipeline.

PMID- 8259505
TI  - Failing to cross the biology-culture gap.

PMID- 8259506
TI  - How p53 suppresses cell growth.

PMID- 8259507
TI  - Gene defect identified in common hereditary colon cancer.

PMID- 8259508
TI  - Switching a bacterial toxin to good use.

PMID- 8259509
TI  - Boning up with organoapatites.

PMID- 8259510
TI  - The future of the fetal tissue bank. The National Advisory Board on Ethics in
      Reproduction.

PMID- 8259511
TI  - Cancer, catenins, and cuticle pattern: a complex connection.

PMID- 8259512
TI  - Protein design by binary patterning of polar and nonpolar amino acids.
AB  - A general strategy is described for the de novo design of proteins. In this
      strategy the sequence locations of hydrophobic and hydrophilic residues were
      specified explicitly, but the precise identities of the side chains were not
      constrained and varied extensively. This strategy was tested by constructing a
      large collection of synthetic genes whose protein products were designed to fold
      into four-helix bundle proteins. Each gene encoded a different amino acid
      sequence, but all sequences shared the same pattern of polar and nonpolar
      residues. Characterization of the expressed proteins indicated that most of the
      designed sequences folded into compact alpha-helical structures. Thus, a simple
      binary code of polar and nonpolar residues arranged in the appropriate order can
      drive polypeptide chains to collapse into globular alpha-helical folds.

PMID- 8259513
TI  - Attempts to mimic docking processes of the immune system: recognition-induced
      formation of protein multilayers.
AB  - The assemblage of protein multilayers induced by molecular recognition, as seen,
      for example, in the immune cascade, has been mimicked by using streptavidin as a
      docking matrix. For these experiments, this protein matrix was organized on
      liposomes, monolayers at the air-water interface, and self-assembled layers on
      gold, all three containing biotin lipids. The docking of streptavidin to biotin
      at liposomal surfaces was confirmed by circular dichroism. Mixed double and
      triple layers of streptavidin, concanavalin A, antibody Fab fragments, and
      hormones are prepared at the air-water interface and on gold surfaces and were
      characterized by fluorescence microscopy and plasmon spectroscopy. With the use
      of biotin analogs that have lower binding constants it has been possible to
      achieve multiple formation and competitive replacement of the oriented protein
      assemblages.

PMID- 8259514
TI  - The role of backbone flexibility in the accommodation of variants that repack the
      core of T4 lysozyme.
AB  - To understand better how the packing of side chains within the core influences
      protein structure and stability, the crystal structures were determined for eight
      variants of T4 lysozyme, each of which contains three to five substitutions at
      adjacent interior sites. Concerted main-chain and side-chain displacements, with
      movements of helical segments as large as 0.8 angstrom, were observed. In
      contrast, the angular conformations of the mutated side chains tended to remain
      unchanged, with torsion angles within 20 degrees of those in the wild-type
      structure. These observations suggest that not only the rotation of side chains
      but also movements of the main chain must be considered in the evaluation of
      which amino acid sequences are compatible with a given protein fold.

PMID- 8259515
TI  - Modulation of calmodulin plasticity in molecular recognition on the basis of x
      ray structures.
AB  - Calmodulin is the primary calcium-dependent signal transducer and regulator of a
      wide variety of essential cellular functions. The structure of calcium-calmodulin
      bound to the peptide corresponding to the calmodulin-binding domain of brain
      calmodulin-dependent protein kinase II alpha was determined to 2 angstrom
      resolution. A comparison to two other calcium-calmodulin structures reveals how
      the central helix unwinds in order to position the two domains optimally in the
      recognition of different target enzymes and clarifies the role of calcium in
      maintaining recognition-competent domain structures.

PMID- 8259516
TI  - Dense nonsymmetrical DNA methylation resulting from repeat-induced point mutation
      in Neurospora.
AB  - Cytosine methylation has been implicated in epigenetic control of gene expression
      in animals, plants, and fungi. It has been assumed that all methylation in
      eukaryotes is at symmetrical sequences such as CpG/GpC, because this can explain
      perpetuation of methylation states. Here the bisulfite genomic sequencing method
      was used to examine methylation in DNA from a Neurospora gene exposed to repeat
      induced point mutation. 5-Methylcytosine was not limited to symmetrical sites and
      individual molecules showed different patterns and amounts of modification. The
      methylation extended beyond the mutated region and even beyond the edge of the
      duplicated segment.

PMID- 8259517
TI  - Initiation at closely spaced replication origins in a yeast chromosome.
AB  - Replication of eukaryotic chromosomes involves initiation at origins spaced an
      average of 50 to 100 kilobase pairs. In yeast, potential origins can be
      recognized as autonomous replication sequences (ARSs) that allow maintenance of
      plasmids. However, there are more ARS elements than active chromosomal origins.
      The possibility was examined that close spacing of ARSs can lead to inactive
      origins. Two ARSs located 6.5 kilobase pairs apart can indeed interfere with each
      other. Replication is initiated from one or the other ARS with equal probability,
      but rarely (< 5%) from both ARSs on the same DNA molecule.

PMID- 8259518
TI  - Association of the APC gene product with beta-catenin.
AB  - Mutations in the human APC gene are linked to familial adenomatous polyposis and
      to the progression of sporadic colorectal and gastric tumors. To gain insight
      into APC function, APC-associated proteins were identified by immunoprecipitation
      experiments. Antibodies to APC precipitated a 95-kilodalton protein that was
      purified and identified by sequencing as beta-catenin, a protein that binds to
      the cell adhesion molecule E-cadherin. An antibody specific to beta-catenin also
      recognized the 95-kilodalton protein in the immunoprecipitates. These results
      suggest that APC is involved in cell adhesion.

PMID- 8259519
TI  - Association of the APC tumor suppressor protein with catenins.
AB  - Mutations of APC appear to initiate sporadic and inherited forms of human
      colorectal cancer. Although these mutations have been well characterized, little
      is known about the function of the APC gene product. Two cellular proteins that
      associate with APC were identified by nucleotide sequence analysis and peptide
      mapping as the E-cadherin-associated proteins alpha- and beta-catenin. A 27
      residue fragment of APC containing a 15-amino acid repeat was sufficient for the
      interaction with the catenins. These results suggest an important link between
      tumor initiation and cell adhesion.

PMID- 8259520
TI  - Elements of the yeast pheromone response pathway required for filamentous growth
      of diploids.
AB  - Transmission of an external signal from receptors to downstream targets is often
      mediated by a conserved set of protein kinases that act in sequence (a kinase
      cascade). In haploid strains of Saccharomyces cerevisiae, a signal initiated by
      peptide pheromones is transmitted through this kinase cascade to a transcription
      factor STE12, which is required for the expression of many mating-specific genes.
      Here it was shown that in diploids some of the same kinases and STE12 are
      required for filamentous growth, but the pheromone receptors and guanosine
      triphosphate-binding protein are not required for filament formation. Thus, a
      similar kinase cascade is activated by different signals in haploids and diploids
      and mediates different developmental outcomes in the two cell types.

PMID- 8259521
TI  - Mutations that allow disulfide bond formation in the cytoplasm of Escherichia
      coli.
AB  - Disulfide bonds are rarely found in cytoplasmic proteins. Mutations were selected
      for in Escherichia coli that allow disulfide bond formation in the cytoplasm. In
      the presence of these mutations, export-defective versions of alkaline
      phosphatase and mouse urokinase were able to fold into their enzymatically active
      conformations in the cytoplasm because their disulfide bonds were formed. The
      mutations were mapped to the gene for thioredoxin reductase and diminish or
      eliminate the activity of this enzyme. Thioredoxin itself was found to be
      unnecessary for this disulfide bond formation. Thioredoxin reductase, but not
      thioredoxin, is thus implicated in keeping cysteines reduced in cytoplasmic
      proteins.

PMID- 8259522
TI  - The learning of categories: parallel brain systems for item memory and category
      knowledge.
AB  - A fundamental question about cognition concerns how knowledge about a category is
      acquired through encounters with examples of the category. Amnesic patients and
      control subjects performed similarly at classifying novel patterns according to
      whether they belonged to the same category as a set of training patterns. In
      contrast, the amnesic patients were impaired at recognizing which dot patterns
      had been presented for training. Category learning appears to be independent of
      declarative (explicit) memory for training instances and independent of the brain
      structures essential for declarative memory that are damaged in amnesia.
      Knowledge about categories can be acquired implicitly by cumulating information
      from multiple examples.

PMID- 8259523
TI  - Kinetics of the uptake of [3H]paroxetine in the rat brain.
AB  - Paroxetine, an antidepressant with a high affinity for serotonin (5-HT) re-uptake
      sites, is a potential tracer of these sites. We determined the kinetic properties
      of [3H]paroxetine in rat brain in vivo. Relative to [14C]iodo-antipyrine, the
      brain uptake index (BUI) of [3H]paroxetine was 60-70%. The unidirectional blood
      clearance of [3H]paroxetine were 0.05-0.12 ml g-1 min-1, lower than expected from
      the BUI values. The steady state volume of distribution was 3.5 ml hg-1 in the
      diencephalon and 1.8 ml g-1 in the cerebellum, suggesting a binding potential of
      unity. Autoradiographs at four hours after [3H]paroxetine injection (300 microCi,
      i.p.) revealed heterogeneous binding consistent with the calculated binding
      potentials. Binding was nearly absent from cerebellum and was highest in the
      dorsal raphe, superior colliculus, dorsal hypothalamus, and entorhinal cortex,
      but did not reach equilibrium in four hours of tracer circulation. The specific
      binding relative to vermis was displaced by pretreatment with fluoxetine (10
      mg/kg, i.p.).

PMID- 8259524
TI  - In vivo imaging of baboon and human dopamine transporters by positron emission
      tomography using [11C]WIN 35,428.
AB  - [11C]WIN 35,428 was evaluated as a specific in vivo radioligand for the dopamine
      transporter site by PET scanning in nonhuman primates and humans. In studies with
      a baboon (Papio anubis), [11C]WIN 35,428 accumulated in brain regions containing
      dopamine transporters, i.e., the striata. This accumulation was partially blocked
      by prior administration of (-)cocaine (4 mg/kg, i.v.). Placement of a unilateral
      lesion of dopamine-containing nerve terminals with MPTP resulted in a unilateral
      reduction in [11C]WIN 35,428 accumulation in the striatum on the side of the
      lesion. Imaging of D2 dopamine receptors with [11C]NMSP in the same MPTP-treated
      animals showed much less reduction in the postsynaptic D2 dopamine receptors as
      compared to the much larger reduction in the dopamine transporters labeled with
      [11C]WIN 35,428. A total of ten normal human volunteers (five males and five
      females) with ages ranging from 19 to 81 years were studied. The
      caudate/cerebellar and putamen/cerebellar ratios ranged from 4.4 to 5.7 90 min
      after injection of the tracer. Preliminary kinetic modeling with arterial plasma
      sampling resulted in an average binding potential (k3/k4) of 4.98 in the caudate
      nucleus and 5.13 in putamen. To demonstrate in vivo blockade with dopamine
      reuptake inhibitors, two subjects received prior oral doses of 6 mg mazindol.
      Subject 5 had significant reductions of 29% in the caudate/cerebellar ratio at 90
      min, 35% in the putamen/cerebellar ratio at 90 min, 45% in the caudate k3/k4
      ratio from 6.7 to 3.7, and 46% in the putamen k3/k4 from 4.7 to 2.5. Subject 8
      had significant reductions of 20% in both the caudate/cerebellar ratio and the
      putamen/cerebellar ratio at 90 min. During the human PET studies, a number of
      neuropsychological tests and physiological measurements were performed. No
      significant changes were found after administration of the [11C]WIN 35,428 alone.
      Taken together, these data indicate that [11C]WIN 35,428 is a promising
      radioligand for future studies of neuropsychiatric disorders that involve the
      dopamine transporter site.

PMID- 8259525
TI  - Prenatal cocaine produces deficits in serotonin mediated neuroendocrine responses
      in adult rat progeny: evidence for long-term functional alterations in brain
      serotonin pathways.
AB  - Cocaine produces biochemical alterations in brain serotonin (5-HT) neurons. Since
      5-HT is critical to the development of fetal 5-HT neurons and target tissues, we
      hypothesized that in utero exposure to cocaine could result in long-term
      alterations in postnatal 5-HT systems. Pregnant Sprague-Dawley rats were
      administered either saline or (-)cocaine (15 mg/kg, s.c., b.i.d.) from
      gestational day 13 to 20. Prenatal cocaine exposure did not alter litter size,
      gender number, or progeny birth weights. Functional alterations in serotonergic
      systems were determined in postnatal day (PD) 70 male progeny by measuring
      changes in 5-HT mediated plasma hormones following a single 8 mg/kg injection of
      the 5-HT releaser p-chloroamphetamine (PCA). Cocaine exposed male progeny
      exhibited significant reductions in adrenocorticotropic hormone (ACTH, -43%) and
      renin (-62%) responses to PCA. However, no alterations were observed in the
      corticosterone or prolactin response to PCA. In utero exposure to cocaine did not
      alter basal levels of ACTH, renin, corticosterone, or prolactin. There were no
      significant differences in the density of either hypothalamic or cortical 5-HT
      uptake sites. Likewise, there were no significant differences in the densities of
      any of the 5-HT1 receptor subtypes or in the density of 5-HT2 receptors in
      cortex. These data, which provide the first demonstration of deficits in 5-HT
      mediated neuroendocrine function in adult progeny following in utero exposure to
      cocaine, indicate long-term functional alterations of brain 5-HT systems.

PMID- 8259526
TI  - Inhibition of A9 and A10 dopamine cells by the cholecystokinin-B antagonist
      LY262691: mediation through feedback pathways from forebrain sites.
AB  - The diphenylpyrazolidinone cholecystokinin-B (CCK-B) antagonist LY262691 has been
      shown to decrease the number of spontaneously active dopamine (DA) cells in the
      ventral tegmental area (A10) and substantia nigra (A9) of the anesthetized rat.
      In the present study, we examined the localization of the receptors mediating
      these effects of LY262691 on A9 and A10 DA cells. In one group of anesthetized
      rats, the effects of systemic administration of LY262691 on the number of
      spontaneously active A9 or A10 DA cells was determined using extracellular,
      single-unit recordings after radio frequency lesions were placed in the nucleus
      accumbens, caudate-putamen, or medial prefrontal cortex. Lesions of the caudate
      putamen blocked the effects of systemically administered LY262691 on the number
      of spontaneously active A9, but not A10, DA cells. Conversely, lesions of the n.
      accumbens blocked the effects of systemically administered LY262691 on A10, but
      not A9, DA cells. Lesions of the medial prefrontal cortex blocked the effects of
      systemically administered LY262691 on both A9 and A10 DA cells. In a separate
      group of anesthetized rats, the number of spontaneously active A9 or A10 DA cells
      was determined after LY262691 was microinjected into the n. accumbens, caudate
      putamen, or medial prefrontal cortex. Microinjection of LY262691 into the caudate
      putamen led to a significant decrease in the number of spontaneously active A9,
      but not A10, DA cells. Conversely, microinjection of LY262691 into the n.
      accumbens or medial prefrontal cortex led to a significant decrease in the number
      of spontaneously active A10, but not A9, DA cells.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8259527
TI  - Contributions of empirical research to medical ethics.
AB  - Empirical research pertaining to cardiopulmonary resuscitation (CPR), clinician
      behaviors related to do-not-resuscitate (DNR) orders and substituted judgment
      suggests potential contributions to medical ethics. Research quantifying the
      likelihood of surviving CPR points to the need for further philosophical analysis
      of the limitations of the patient autonomy in decision making, the nature and
      definition of medical futility, and the relationship between futility and
      professional standards. Research on DNR orders has identified barriers to the
      goal of patient involvement in these life and death discussions. The initial data
      on surrogate decision making also points to the need for a reexamination of the
      moral basis for substituted judgment, the moral authority of proxy decision
      making and the second-order status of the best interests standard. These examples
      of empirical research suggest that an interplay between empirical research,
      ethical analysis and policy development may represent a new form of
      interdisciplinary scholarship to improve clinical medicine.

PMID- 8259528
TI  - Assessing empirical research in bioethics.
AB  - Empirical research can aid ethical reflection in bioethics by identifying issues,
      by seeing how they are currently resolved, and by assessing the consequences of
      these current resolutions. This potential can be misused when the ethical issues
      in question are fundamentally non-consequentialist or when they are
      consequentialist but the empirical research fails to address the important
      consequences. An example of the former problem is some recent studies about bad
      consequences resulting from commercialized living kidney donor programs. These
      consequences could be avoided, but the crucial non-consequentialist ethical
      issues about exploitation and commercialization would still remain. Examples of
      the latter problem are provided by recent studies of the allocation of ICU beds
      and of physician deception, where important consequences were not adequately
      studied.

PMID- 8259529
TI  - The educational philosophies behind the medical humanities programs in the United
      States: an empirical assessment of three different approaches to humanistic
      medical education.
AB  - This study investigates the three major educational philosophies behind the
      medical humanities programs in the United States. It summarizes the
      characteristics of the Cultural Transmission Approach, the Affective
      Developmental Approach, and the Cognitive Developmental Approach. A questionnaire
      was sent to 415 teachers of medical humanities asking for their perceptions of
      the amount of time and effort devoted by their programs to these three
      philosophical approaches. The 234 responses constituted a 54.6% return. The
      approximately 80:20 gender ratio of males to females and other demographic data
      on age and educational background were consistent with other studies of the field
      of medical humanities. Reflections on the results in Table II indicate that some
      changes need to take place in the teaching of the medical humanities if the
      perceived ideal is to be achieved. In order for the current teachers of the
      medical humanities to think that the appropriate philosophies behind the teaching
      of the medical humanities are being implemented as they should be, much less time
      and effort need to be devoted to the Cultural Transmission Approach. With no
      other published reports on the educational philosophies behind the medical
      humanities programs, this study created a new knowledge base about this
      relatively young and rapidly emerging field.

PMID- 8259530
TI  - Should we change the human genome?
AB  - Should we change the human genome? The most general arguments against changing
      the human genome are here in focus. Distinctions are made between positive and
      negative gene therapy, between germ-line and somatic therapy, and between therapy
      where the intention is to benefit a particular individual (a future child) and
      where the intention is to benefit the human gene-pool. Some standard arguments
      against gene-therapy are dismissed. Negative somatic therapy is not
      controversial. Even negative, germ-line therapy is endorsed, if the intention is
      to cure a certain individual (a future child). In rare cases, positive therapy on
      somatic cells may be warranted. Germ-line therapy may become a valuable method of
      preventing harm, through 'genetic vaccination'. If safe methods evolve, it is
      harmless (though vain), to try to achieve more ambitious goals. Prospective
      parents should not be prevented from exercising this harmless kind of parental
      authority. The paper concludes: There is a moral limit to how much we ought to
      manipulate the human genome, however. We ought not to jeopardize the continued
      existence of mankind. We ought not to develop methods of germ-line therapy
      intended in a radical manner to improve human nature, and we ought to leave to
      prospective parents to decide in individual cases what kind of intervention shall
      take place.

PMID- 8259531
TI  - Definition and classification of cancer: monothetic or polythetic?
AB  - Since the microbiological revolution, most infectious diseases have been defined
      and classified according to an etiologic criterion, i.e. the identification of
      single, external "necessary" causes (for example, Mycobacterium for
      tuberculosis). This is not the case with cancer. Not only external "necessary"
      causes of cancer have not been identified, but also the morphological
      classification cannot be based on univocal criteria. Although "neoplasia" and
      "anaplasia" appear to be universal attributes of cancer, these events are only
      quantitative. Neoplastic growth can be fast or slow (development may take weeks
      or years), and tissue pathologies are difficult to detect from normal tissue in
      some cancers but are obvious in others. Common special properties of anaplasia
      appear to be concealed in the wide range of morphologies. In the absence of a
      coherent morphological definition, and of external necessary causes (such as
      bacteria for infectious diseases), a mechanistic definition could be adopted.
      However, unless molecular biology discovers specific mechanistic steps in
      carcinogenesis, which indicate the existence of "necessary" events in
      carcinogenesis, we cannot adopt a univocal (monothetic) definition of cancer. The
      alternative is to use a polythetic definition, according to Wittgenstein's model
      of a "long rope twisted together out of many shorter fibres."

PMID- 8259532
TI  - The logic of the medical research article.
AB  - As do all forms of science, medical theories have a factual as well as a logical
      basis. New information is presented in medical research articles. These papers
      have three separate arguments: the argument of the hypothesis, the argument of
      the experimental protocol, and the argument of the hypothesis's judgement. These
      arguments may be examples of the hypothetico-deductive or confirmational model of
      scientific interference. The logical form of these arguments are informal and
      inductive rather than formal and deductive. Understanding the nature of the logic
      of the medical research article may help avoid erroneous conclusions.

PMID- 8259533
TI  - Associations of factor VIII and von Willebrand factor with age, race, sex, and
      risk factors for atherosclerosis. The Atherosclerosis Risk in Communities (ARIC)
      Study.
AB  - Several coagulation proteins have been implicated as possible risk factors for
      the development of atherosclerotic diseases, among which are factor VIII and von
      Willebrand factor. As part of the Atherosclerosis Risk in Communities (ARIC)
      Study, a prospective study designed to assess risk factors for the development of
      atherosclerotic diseases, baseline measurements of factor VIII and von Willebrand
      factor (vWF) were performed to determine their relationship to the development of
      atherosclerosis. We herein report the associations of factor VIII and vWF with
      constitutional, lifestyle, and biochemical factors. Factor VIII and vWF were
      strongly correlated with each other (r = 0.73), and, therefore, had similar
      associations with risk factors. Mean levels of both factors were higher in women
      than in men, in blacks than in whites, and increased with age. In univariate
      analysis, both were positively associated with diabetes, body mass index, waist
      to-hip ratio, serum insulin, and plasma triglycerides. Both were negatively
      associated with alcohol intake, educational level, physical activity (with some
      exceptions), and HDL-cholesterol. No correlations were observed between factor
      VIII or vWF and plasma LDL-cholesterol or lipoprotein(a). Although factor VIII
      was negatively associated with smoking in both sexes, vWF was not associated with
      smoking status. Most of these associations were confirmed in multivariate
      analysis. The strongest associations observed were of factor VIII and vWF with
      race and diabetes. In multivariate analysis, blacks had factor VIII and vWF
      levels 15 to 18 percentage points higher than whites, and diabetics had factor
      VIII and vWF levels 11 to 18 percentage points higher than non
      diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259534
TI  - Treatment of severe venous thrombo-embolism with intravenous Hirudin (HBW 023):
      an open pilot study.
AB  - Recombinant Hirudin (rH) is an anticoagulant agent with a specific antithrombin
      activity independent of antithrombin III. We report the results of the first open
      pilot study on the curative treatment of acute venous thrombo-embolism (VTE) with
      rH (HBW 023) in ten patients. The dose of rH tested was 0.07 mg/kg (i.v. bolus)
      followed by 0.05 mg kg-1 h-1 (i.v. infusion) for 5 days, without activated
      partial thromboplastin time (APTT) adjustment. Within the trial, no death, VTE
      recurrence or major bleeding was observed; lung scan pulmonary vascular
      obstruction improved from 44 to 37%, whereas the venographic Marder score was
      unchanged; APTT ratio ranged between 1.2 and 2.8. The dose of rH assessed in this
      study seems to be safe and efficient in the treatment of acute VTE.

PMID- 8259535
TI  - The in vitro production of thromboxane B2 by platelets of diabetic patients is
      normal at physiological concentrations of ionized calcium.
AB  - Platelets of patients with diabetes and no evidence of macroangiopathy produce
      normal amounts of thromboxane (Tx) B2 in vivo, whereas they usually show
      increased production in vitro. Since in vitro studies have been usually performed
      in citrated PRP, we tested the hypothesis that the discrepancy between in vivo
      and in vitro studies is due to the low concentration of plasma ionized calcium
      ([Ca2+]o) that is present in citrated PRP. In fact, low [Ca2+]o artifactually
      potentiates the platelet TxB2 production in vitro. Forty patients with diabetes
      mellitus and 37 matched controls were studied. Blood was anticoagulated with
      citrate, the thrombin inhibitor D-phenylalanyl-l-prolyl-l-chloromethylketone
      (PPACK) or both anticoagulants. Platelet aggregation, release of 14C-serotonin
      and TxB2 production were induced in platelet rich plasma (PRP) by several
      agonists. The following results were obtained: i) Citrated PRP: Arachidonic acid
      induced aggregation (p < 0.01) and TxB2 production (p < 0.02) were significantly
      greater in patients than in controls. No statistically significant differences
      were found with other agonists. ii) PPACK PRP: No statistically significant
      difference was found between diabetic platelets and controls. iii) PPACK plus
      citrate PRP: The results were not different from those obtained with citrate
      alone. Therefore, our results show that diabetic platelets produce normal amounts
      of TxB2 in vitro when the [Ca2+]o is physiological.

PMID- 8259536
TI  - Venous thromboembolism and high grade gliomas.
AB  - A retrospective study was done to determine the incidence of and the risk factors
      predisposing to clinical venous thromboembolism (VTE) in patients treated for
      high grade gliomas. Medical records of 68 consecutive patients diagnosed and
      treated at Saint Francis Hospital and Medical Center from January 1986 to June
      1991 were reviewed. The follow up was to time of death or at least 6 months (up
      to December 1991). All clinically suspected episodes of VTE were confirmed by
      objective tests. Sixteen episodes of VTE were detected in 13 patients for an
      overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two
      tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher
      exact test) were statistically significant risk factors for the development of
      VTE. Thrombotic events were more likely to occur in the paretic limb and this
      difference was statistically significant (p = 0.00049, chi square test, with
      Yates correction). No major bleeding complications were seen in the nine episodes
      treated with long term anticoagulation. We conclude that venous thromboembolic
      complications are frequently encountered in patients being treated for high grade
      gliomas and the presence of paresis and the administration of chemotherapy
      increases the risk of such complications.

PMID- 8259537
TI  - A new type of congenital dysfibrinogen, fibrinogen Bremen, with an A alpha Gly-17
      to Val substitution associated with hemorrhagic diathesis and delayed wound
      healing.
AB  - We have identified a new type of A alpha Gly-17 to Val substitution in a
      congenital dysfibrinogen, fibrinogen Bremen, derived from a 15-year-old boy
      having manifested easy bruising and delayed wound healing. The functional
      abnormality was characterized by altered fibrin monomer polymerization, which
      became evident by increasing the salt concentration and pH. A synthetic
      tetrapeptide with a sequence of the amino-terminal segment of normal fibrin alpha
      chain, Gly-Pro-Arg-Val, substantially inhibited polymerization of both normal and
      the patient-derived fibrin monomers. A synthetic tetrapeptide with the Bremen
      type sequence of Val-Pro-Arg-Val inhibited polymerization of the patient's fibrin
      monomers partially at a peptide: fibrin monomer molar ratio of 4,000:1, and that
      of normal one at a much higher ratio of 10,000:1. Likewise, a synthetic peptide
      Ala-Pro-Arg-Val with a replacement of the Gly residue by another aliphatic amino
      acid Ala inhibited similarly the patient's fibrin monomer polymerization. Thus,
      the hypothetical two-pronged socket-like structure consisting of the alpha-amino
      group of the amino-terminal Gly and the guanidino group of an Arg at position 3
      of the normal fibrin alpha-chain seems to be restored considerably in the mutant
      fibrin alpha-chain at low ionic strengths and pH's, despite the replacement of
      the amino-terminal Gly by another aliphatic amino acid Val.

PMID- 8259538
TI  - Comparison of real-time B-mode ultrasonography and Doppler ultrasound with
      contrast venography in the diagnosis of venous thrombosis in symptomatic
      outpatients.
AB  - In a prospective study, we compared real-time B-mode ultrasonography, using the
      simple criteria of common femoral and popliteal vein compressibility (Compression
      US), and Doppler ultrasound, using a standardized technique (Doppler US), with
      contrast venography in 158 consecutive outpatients symptomatic for deep-vein
      thrombosis of the lower limbs (DVT). For proximal vein thrombosis, the
      sensitivities documented for Compression US and Doppler US were 100% (95% CI: 90%
      to 100%) and 89% (95% CI: 76% to 96%), respectively. This difference is not
      statistically significant (p = 0.056). For all thrombi (including isolated calf
      vein thrombosis), however, the sensitivity of Compression US was significantly
      higher than that of Doppler US (95% and 76%, respectively; p < 0.04). Compression
      US was normal in all patients with normal venogram (specificity, 100%; 95% CI:
      95% to 100%), while Doppler US was abnormal in two patients with normal venogram
      (specificity, 98%; 95% CI: 92% to 100%). The specificities of the two tests did
      not differ significantly. The results of our comparison suggest that Compression
      US is superior to Doppler US in the detection of DVT in symptomatic outpatients.

PMID- 8259539
TI  - A comparative analysis of D-dimer assays in patients with clinically suspected
      pulmonary embolism.
AB  - To avoid angiography in patients with clinically suspected pulmonary embolism and
      non-diagnostic lung scan results, the use of D-dimer has been advocated. We
      assessed plasma samples of 151 consecutive patients with clinically suspected
      pulmonary embolism. Lung scan results were: normal (43), high probability (48)
      and non-diagnostic (60; angiography performed in 43; 12 pulmonary emboli).
      Reproducibility, cut-off values, specificity, and percentage of patients in whom
      angiography could be avoided (with sensitivity 100%) were determined for two
      latex and four ELISA assays. The latex methods (cut-off 500 micrograms/l) agreed
      with corresponding ELISA tests in 83% (15% normal latex, abnormal ELISA) and 81%
      (7% normal latex, abnormal ELISA). ELISA methods showed considerable within- (2
      17%) and between-assay variation (12-26%). Cut-off values were 25 micrograms/l
      (Behring), 50 micrograms/l (Agen), 300 micrograms/l (Stago) and 550 micrograms/l
      (Organon). Specificity was 14-38%; in 4-15% of patients angiography could be
      avoided. We conclude that latex D-dimer assays appear not useful, whereas ELISA
      methods may be of limited value in the exclusion of pulmonary embolism.

PMID- 8259541
TI  - Recombinant human soluble thrombomodulin delivers bounded thrombin to
      antithrombin III: thrombomodulin associates with free thrombin and is recycled to
      activate protein c.
AB  - Recombinant human soluble thrombomodulin (rhs-TM), having no transmembrane domain
      or chondroitin sulfate, was expressed in Chinese hamster ovary cells.
      Interactions between rhs-TM, thrombin (Th), protein C (PC) and antithrombin III
      (ATIII) were studied. Equilibrium between rhs-TM and Th had no detectable time
      lag in clotting inhibition (Kd = 2.6 nM) or PC activation (Kd = 22 nM), while
      ATIII inhibited Th at a bimolecular rate constant = 5,200 M-1s-1 (Kd < 0.2 nM). A
      mixture of ATIII, Th and rhs-TM showed that ATIII reacted with Th slower than rhs
      TM, whose presence did not affect the reaction between ATIII and Th. In a mixture
      of rhs-TM, ATIII and PC, the repeated addition of Th caused the repeated
      activation of PC; which was consistent with the simulation based on the
      assumption that rhs-TM is recycled as a Th cofactor. From these results, we
      concluded that upon inhibition of the rhs-TM-Th complex by ATIII, rhs-TM is
      released to recombine with free Th and begins to activate PC, while the Th-ATIII
      complex does not affect rhs-TM-Th equilibrium.

PMID- 8259540
TI  - Human leukocyte elastase and cathepsin G inactivate factor VII by limited
      proteolysis.
AB  - The effect of supernatant from phorbol myristate acetate (PMA) stimulated human
      polymorphonuclear granulocytes (PMN) on human factor VII was studied in vitro.
      The supernatant caused a rapid loss in factor VII coagulant activity by the
      action of human leukocyte elastase (HLE) and cathepsin G in the supernatant, as
      demonstrated by the use of specific inhibitors of the two serine proteases,
      respectively. Preincubation of the supernatant with the elastase inhibitor and
      the cathepsin G inhibitor preserved 80% and 25% of the clotting activity,
      respectively. Calcium protected factor VII completely from the supernatant
      mediated inactivation. Cathepsin G and HLE purified from PMN each destroyed the
      coagulant activity of factor VII when added to a non-plasma system. There were,
      however, no effect on factor VII activity when cathepsin G was added to plasma.
      Polyacrylamide gel electrophoresis in the presence of SDS indicated that HLE and
      cathepsin G cleaved the zymogen in the same manner, producing (a) peptide(s) of
      low molecular mass and a single large product of 48 kDa. Preincubation of factor
      VII with calcium ions inhibited the proteolytic action of HLE and cathepsin G. It
      is suggested that HLE and cathepsin G from activated granulocytes may be partly
      responsible for the loss in factor VII activity that is observed during sepsis.

PMID- 8259542
TI  - Evidence that the protein C activation pathway amplifies the inhibition of
      thrombin generation by recombinant human thrombomodulin in plasma.
AB  - Thrombomodulin (TM) is a cofactor for the thrombin-catalyzed activation of
      anticoagulant protein C. However, we have no evidence that thrombomodulin
      actually activates protein C during blood coagulation processing, nor do we know
      whether this activated protein C acts as an anticoagulant. We studied the
      inhibitory action of recombinant human soluble TM (rhs-TM) on thrombin generation
      in whole plasma. Human plasma was activated with small amounts of tissue factor
      using phospholipid vesicles in place of activated platelets. Thrombin generation
      was observed. The addition of only 2 nM of rhs-TM prevented rapid generation of
      thrombin and reduced the total amount of thrombin generated. In order to study
      the influence of the protein C activation pathway on this inhibitory action of
      rhs-TM, protein C-depleted plasma was used. rhs-TM had little inhibitory effect
      on protein C-depleted plasma. However, the addition of protein C caused a delay
      in thrombin generation and a reduction of the maximum thrombin concentration. We
      concluded that the anticoagulant activity of rhs-TM was amplified by the protein
      C activation pathway.

PMID- 8259543
TI  - Functional characterization of a variant prekallikrein (PK Zurich).
AB  - The plasma of a 68-year-old man with cross reacting material (CRM)-positive
      prekallikrein (PK) deficiency was studied. PK clotting activity was < 0.01 U/ml,
      and PK antigen was 0.1 U/ml. No circulating anticoagulant against PK was
      detectable. The abnormal PK molecule, denoted as prekallikrein Zurich, was
      partially characterized by immunological and functional studies on the
      propositus' plasma. Immunoblotting analysis showed the abnormal PK being a single
      chain molecule of the same M(r) (80 kDa) as normal PK. Dextran sulfate activation
      of the propositus' plasma did not lead to proteolytic cleavage of the variant PK
      molecule, in contrast to dextran sulfate activation of a mixture of 1 volume
      normal plasma and 9 volumes CRM-negative PK deficient plasma. Agarose gel
      electrophoresis followed by immunoblotting demonstrated that PK Zurich was
      complexed with high molecular weight kininogen similarly to PK in normal plasma.
      Incubation of the propositus' plasma with purified beta-FXIIa resulted in
      impaired cleavage of PK Zurich when compared with PK hydrolysis in a mixture of
      10% normal plasma and 90% CRM-negative PK deficient plasma. Moreover,
      proteolytically cleaved PK Zurich showed no enzymatic activity against factor XII
      and high molecular weight kininogen. These studies show that the functional
      defect of prekallikrein Zurich is due to an impaired cleavage by activated factor
      XII and probably the lack of enzymatic activity of the cleaved variant molecule.

PMID- 8259544
TI  - Evaluation of factor VIII deficient plasmas.
AB  - Immunodepleted plasmas from Organon Teknika, Dade, Stago, Diagen and the Scottish
      National Blood Transfusion Service (SNBTS), and haemophilic plasma from Immuno
      were compared by several laboratories with haemophilic plasma from local donors
      as substrates in one-stage factor VIII assays. Five clinical plasma samples and
      four concentrates were assayed against British Standard plasma and International
      Standard concentrate. Potencies of all plasma samples were not significantly
      different from those with local haemophilic plasma for Immuno, Organon Teknika,
      Stago and SNBTS substrates. Dade differed from haemophilic on one sample and
      Diagen on three. Buffer blank times and slopes of standard lines were similar
      with all substrates. A positive drift between the beginning and end of the assay
      was found with the Immuno substrate and a negative drift with the Organon Teknika
      substrate. In the concentrate study results for all substrate plasmas were not
      significantly different from haemophilic on the intermediate purity and
      conventional high purity products. On the monoclonal and recombinant products,
      there was a tendency for the immunodepleted substrates to give lower potencies
      than the haemophilic, and significant differences were found with Dade and Stago
      on the monoclonal concentrate, and with Dade, Stago and Diagen on the recombinant
      concentrate. Overall, this study indicates that most commercially available
      substrate plasmas are suitable as replacements for locally collected haemophilic
      plasma in one-stage assays of clinical samples, and of intermediate purity and
      conventional high purity concentrates. For assays of very high purity
      concentrates (monoclonal and recombinant), haemophilic plasma is preferable as
      some immunodepleted plasmas give low results.

PMID- 8259545
TI  - Cross-linked alpha s gamma t-chain hybrids in plasma clots studied by 1D- and 2D
      electrophoresis and western blotting.
AB  - Fibrinogen and fibrin related chains in reduced human plasma as well as the bonds
      interlinking partially cross-linked fibrin from plasma clots have been studied by
      means of 1D- and 2D electrophoresis and Western blotting. Immunovisualization of
      reduced plasma or partially cross-linked fibrin with monoclonal antibodies
      specific for the alpha-chains or the gamma-chains have shown that several bands
      represent material belonging to both chains. In order to decide whether these
      bands constitute alpha gamma-chain hybrids or superimposed alpha- and gamma-chain
      dimers, the cross-linked material was separated according to both isoelectric
      point (pI) and molecular weight (MW) using Pharmacia's Multiphor II system.
      Western blotting of the second dimension gels revealed that partially cross
      linked fibrin contains alpha s gamma t-chain hybrids and gamma-polymers, in
      addition to the well-known gamma-dimers and alpha-polymers. The main alpha s
      gamma t-chain hybrid has a pI between that of the alpha- and the gamma-chains, a
      MW of about 200 kDa and contains A alpha-chains with intact fibrinopeptide A
      (FPA). It was also observed that soluble fibrinogen/fibrin complexes as well as
      partially cross-linked fibrin contain degraded alpha-dimers with MWs close to the
      gamma-dimers. These findings demonstrate that factor XIII-catalyzed cross-linking
      of fibrin is a more complex phenomenon than earlier recognized.

PMID- 8259546
TI  - The additive effect of low molecular weight heparins on thrombin inhibition by
      dermatan sulfate.
AB  - The aim of this study was to investigate the mechanism by which the anticoagulant
      activity of dermatan sulfate (DS) is increased by low molecular weight heparin
      (LMWH). In platelet poor plasma, LMWH enhances the effect of DS on thrombin (IIa)
      inhibition as determined by thrombin clotting times and with a chromogenic
      substrate assay. Analysis of the results of the chromogenic assays using either
      the algebraic fractional or the graphic isobole method suggests that LMWH has an
      additive effect on the anti-IIa activity of DS. This additive effect was lost
      when the experiments were repeated in plasma immunodepleted of antithrombin III
      (ATIII), indicating that the anti-IIa activity of LMWH is ATIII-dependent. To
      further explore the mechanism of the interaction between LMWH and DS, 125I
      labeled IIa was added to plasma in the presence or absence of DS and/or LMWH and
      the formation of IIa-inhibitor complexes was assessed using SDS-PAGE followed by
      autoradiography. DS addition selectively increases the formation of heparin
      cofactor II (HCII)-IIa complexes, whereas LMWH enhances ATIII-IIa complex
      generation. Compared to plasma containing DS alone, the formation of ATIII-IIa
      complexes also is increased when the combination of DS and LMWH is added. These
      findings suggest that the additive effect of LMWH on the anti-IIa activity of DS
      reflects their different modes of IIa inhibition; DS potentiates IIa inhibition
      by HCII, while LMWH catalyses ATIII-dependent IIa inactivation. The potential
      clinical significance of these findings requires further investigation.

PMID- 8259547
TI  - The significance of TFPI in clotting assays--comparison and combination with
      other anticoagulants.
AB  - The anticoagulant activities of Tissue Factor Pathway Inhibitor (TFPI), heparin
      and hirudin were compared in intrinsic (APTT) and extrinsic (PT) activated
      clotting assays. In contrast to the thrombin inhibitor hirudin, heparin was 10
      fold more potent in the APTT assay than in the PT assay, indicating that
      inhibition of intrinsic activation is important for the anticoagulant activity of
      heparin as measured in an APTT assay. TFPI was most potent in the PT assay and
      the effect of TFPI was most pronounced in the presence of other anticoagulants
      (heparin and hirudin). The activities of the two natural anticoagulants
      antithrombin III (ATIII) and TFPI were compared in a PT assay with very dilute
      tissue factor. In this assay system TFPI in normal plasma affected the clotting
      time more than ATIII in the plasma. However, when heparin was added ATIII was the
      major anticoagulant, but profound prolongation of the clotting time was only seen
      when TFPI was also added. In an ATIII deficient plasma heparin did not augment
      the effect of TFPI, showing that the increased effect of TFPI in the presence of
      heparin is dependent on the anticoagulant activity of ATIII/heparin. The effect
      of TFPI at prolonged clotting times was also illustrated by the significant
      effect of blocking TFPI in the plasma from warfarin-treated patients. Thus TFPI
      is a major anticoagulant in normal plasma and the effect of TFPI is especially
      seen at prolonged clotting times.

PMID- 8259548
TI  - Pharmacokinetics of full length and two-domain tissue factor pathway inhibitor in
      combination with heparin in rabbits.
AB  - Tissue factor pathway inhibitor (TFPI) is a feed back inhibitor of the initial
      activation of the extrinsic pathway of coagulation. In humans, injection of
      heparin results in a 2-6 fold increase in plasma TFPI and recent studies suggest
      that TFPI may be important for the anticoagulant activity of heparin. Full length
      (FL) TFPI, but not recombinant two-domain (2D) TFPI, has a poly cationic C
      terminus showing very strong heparin binding. Therefore, we have investigated if
      heparin affects the pharmacokinetics of TFPI with and without this C-terminus. FL
      TFPI (608 U/kg) and 2D-TFPI (337 U/kg) were injected intravenously in rabbits
      with and without simultaneous intravenous injections of low molecular weight
      heparin (450 anti-XaU/kg). Heparin decreased the volume of distribution and the
      clearance of FL-TFPI by a factor 10-15, whereas the pharmacokinetics of 2D-TFPI
      were unaffected by heparin. When heparin was administered 2 h following TFPI the
      recovery of FL-TFPI was similar to that found in the group receiving the two
      compounds simultaneously, suggesting that the releasable pool of FL-TFPI is
      removed very slowly in the absence of circulating heparin.

PMID- 8259550
TI  - Distribution of the recombinant coagulation factor 125I-rFVIIa in rats.
AB  - Recombinant human factor VIIa (rFVIIa; NovoSeven) is a two-chain activated
      clotting factor that is used in the treatment of haemophilia. The distribution of
      radioactivity in male and pregnant and non-pregnant female rats has been examined
      by whole-body autoradiography (WBA) after single intravenous doses of 125I
      radiolabelled rFVIIa at a dosage level of ca. 0.1 mg/kg. Concentrations of
      radioactivity were highest in the blood and the highly perfused major thoracic
      and visceral organs and gonads. This distribution of radioactivity was generally
      similar in pregnant and non-pregnant females, and although radioactivity was
      concentrated in the foetal thyroid, it was present in other foetal tissues only
      at trace levels. Radioactivity in thyroid, urinary bladder and gastrointestinal
      tract of all rats was apparently associated with detached 125I-iodide. At early
      sacrifice times (up to 2 h), radioactivity was present in the bone marrow, but at
      later times (6-24 h) it was apparently associated with the mineralised bone
      structures. The quantitative distribution of total and trichloroacetic acid
      precipitable radioactivity in the tissues of rats also was studied after single
      intravenous doses of 125I-rFVIIa and 125I-rFVII, the non-activated single chain
      precursor of FVIIa, which is normally present in the circulation. These studies
      confirmed the WBA findings and showed that the tissue distribution of 125I-rFVII
      and 125I-rFVIIa was similar, indicating that the distribution of rFVIIa during
      therapy would be similar to that produced from endogenous FVII as a physiological
      response to vascular injury.

PMID- 8259549
TI  - Pharmacokinetics of recombinant factor VIIa in the rat--a comparison of bio-,
      immuno- and isotope assays.
AB  - Recombinant human factor VIIa (rFVIIa) is an activated coagulation factor for
      intravenous use as a haemostatic agent in haemophiliacs who generate antibodies
      against factor VIII or IX. Plasma kinetic studies are important for the
      understanding of the action of rFVIIa which is exerted in the vascular
      compartment of the body, more specifically on the vessel walls at the site of
      injury. In the present study, rats were dosed 100 or 500 micrograms/kg 125I
      rFVIIa i.v., without any side effects being observed, and the plasma profile of
      rFVIIa was studied by 3 different assays that were shown to correlate well at
      early times post-dose: trichloroacetic acid (TCA)-precipitable drug-related
      radioactivity, rFVIIa antigen determination by ELISA technique, and the assay of
      clot activity which is the only clinically applicable assay. The plasma
      concentration curve could be resolved into 1-3 exponentials, depending on the
      FVIIa detection principle that was employed. Initially, there was a short (ca. 10
      min) phase of increasing concentrations before the attainment of Cmax. This was
      followed by a plasma recovery (Cmax x plasma volume/dose) in the vicinity of one
      half of the administered dose. The initial volume of distribution (V1)
      corresponded to the vascular compartment whereas the volume of distribution at
      steady state (Vss) was somewhat larger. Whole body clearance (CL-B) of rFVIIa was
      approx. 1 ml/min per kg, and mean residence time (MRT) and the half-life assumed
      to be associated with the loss of biological activity was approx. 1 h and 20-45
      min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259551
TI  - Thrombin stimulates expression of tissue-type plasminogen activator and
      plasminogen activator inhibitor type 1 in cultured human vascular smooth muscle
      cells.
AB  - The effect of thrombin on the fibrinolytic potential of human vascular smooth
      muscle cells (SMC) in culture was studied. SMC of different origin responded to
      thrombin treatment with a dose and time dependent increase in tissue-type
      plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1)
      levels in both cell lysates and conditioned media with maximum effects achieved
      at 10-20 IU/ml thrombin. PAI-1 antigen levels also increased in the extracellular
      matrix of thrombin treated SMC. PAI-2 levels in cell lysates of such SMC were not
      affected by thrombin. The effect was restricted to active thrombin, since DFP
      thrombin and thrombin treated with hirudin showed no increasing effect on t-PA
      and PAI-1 levels in SMC. Enzymatically active thrombin also caused a four-fold
      increase in specific PAI-1 mRNA and a three-fold increase in t-PA mRNA.
      Furthermore we demonstrated the presence of high and low affinity binding sites
      for thrombin on the surface of SMC with a KD = 4.3 x 10(-10)M and 9.0 x 10(4)
      sites per cell and a KD = 0.6 x 10(-8) M and 5.8 x 10(5) sites per cell
      respectively. Thrombin could come in contact with SMC in case of vascular injury
      or following gap formation between endothelial cells. Our data support the idea
      that besides its known proliferative effect for SMC, thrombin could also modulate
      their fibrinolytic system.

PMID- 8259552
TI  - Antigens of tissue plasminogen activator and plasminogen activator inhibitor 1:
      correlates in nonsmoking Japanese and Caucasian men and women.
AB  - We reported in a 1987 preliminary study that tissue plasminogen activator antigen
      was significantly higher in American Caucasian men than in Japanese men. To
      further examine possible differences in fibrinolytic activity between the two
      races, an expanded study was conducted in a total of 300 nonsmoking men and women
      aged 47-69 years in two population-based samples: rural Japanese living in Akita
      and Caucasians living in Minneapolis-St. Paul, MN. Antigens of tissue plasminogen
      activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) were measured.
      Mean t-PA antigen was 2.3 ng/ml higher in Caucasian men than in Japanese men (P <
      0.001), but no race difference was seen for women (P = 0.59). Mean PAI-1 was
      higher in Caucasians than in Japanese for both sexes, and the race difference in
      mean was 1.8 ng/ml for men (P = 0.07) and 4.4 ng/ml for women (P < 0.001). Both t
      PA and PAI-1 were associated positively with body mass index and blood
      triglycerides for all sex-race groups, and positively with alcohol intake for
      Japanese and Caucasian men. Compared to Japanese, Caucasians of both sexes had
      higher levels of body mass index and blood triglycerides, and lower average
      intake of alcohol among men. Even when adjusted for body mass index,
      triglycerides, alcohol and other cardiovascular risk factors, the race difference
      in mean t-PA antigen persisted for men (P < 0.001), as did the difference in mean
      PAI-1 for men (P = 0.03) and women (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259553
TI  - Comparison of the in vitro fibrinolytic activities of low and high molecular
      weight single-chain urokinase-type plasminogen activator.
AB  - The fibrinolytic activity of low molecular weight (LMW) single-chain urokinase
      type plasminogen activator (scu-PA) lacking the epidermal growth factor domain
      and the kringle domain was compared with the activity of high molecular weight
      (HMW) scu-PA. LMW scu-PA was 1-5 times less active than HMW scu-PA in a fibrin
      plate method, in a purified fibrin clot lysis assay and in a plasma clot lysis
      assay. Time course experiments in a chromogenic plasminogen activator assay
      suggested that LMW scu-PA was less sensitive to activation by plasmin than HMW
      scu-PA. This was confirmed in a scu-PA activation test, which showed that at a
      concentration of 40 IU/ml LMW scu-PA required a three-fold higher plasmin
      concentration for 50% activation in 20 min than did HMW scu-PA. Kinetic
      experiments in the presence of 0.1 M NaCl showed non-standard Michaelis-Menten
      kinetics for the activation by plasmin of both HMW and LMW scu-PA. In contrast,
      standard kinetics was observed at 0.15 M NaCl, showing a 2.6-fold lower catalytic
      efficiency for LMW scu-PA than for HMW scu-PA. It is concluded that the plasmin
      activation of LMW scu-PA is about three times slower than the activation of HMW
      scu-PA. This explains, at least partially, the lower fibrinolytic activity of LMW
      scu-PA in comparison with HMW scu-PA.

PMID- 8259554
TI  - Tissue-type plasminogen activator after venous occlusion in pregnancy and
      puerperium.
AB  - Pregnancy is associated with depressed fibrinolysis as judged from the decreased
      fibrinolytic response to venous occlusion. In order to elucidate if this
      decreased response is due to an increase in plasminogen activator inhibitors 1
      and 2 (PAI-1, PAI-2), and/or to decreased release of tissue-type plasminogen
      activator (t-PA) antigen during venous occlusion, 36 women (18 women with normal
      pregnancy and 18 with gestational hypertension without proteinuria) were followed
      during pregnancy and puerperium. In each women a 20 min venous occlusion was
      performed in the second and in the third trimester of pregnancy and 3 days after
      delivery. The increase in t-PA antigen after venous occlusion relative to basal
      value was in the second trimester of pregnancy on average 3.7 fold, in the third
      trimester 4.4 fold, and so not reduced compared to non-pregnant women (3.7 fold
      increase). After delivery the increase in t-PA antigen was significantly enhanced
      (8.5 fold, p < 0.005). The fibrinolytic response to venous occlusion measured by
      euglobulin and t-PA activity was significantly decreased in the third trimester
      compared to non-pregnant values (both p < 0.005) and returned to somewhat higher
      (euglobulin clot lysis) or significantly higher (t-PA activity, p < 0.01) values
      3 days after delivery. Decreased euglobulin and t-PA activity after venous
      occlusion in the third trimester coincided with significant increases in basal
      PAI activity, PAI-1 antigen and PAI-2 antigen (2.9, 2.5 and > 30 fold increase
      relative to non-pregnant values, respectively, all p < 0.001).(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8259555
TI  - Bio-immunoassay for staphylokinase in blood.
AB  - A bio-immunoassay (BIA) for the determination of staphylokinase (STA) activity in
      a plasma milieu has been developed. MA-7H11, a murine monoclonal antibody raised
      against STA, which has a high affinity for STA but does not interfere with the
      complex formation between plasmin(ogen) and STA or with plasminogen activation by
      STA, was coated on microtiter plates at a concentration of 4 micrograms/ml. STA
      containing samples were incubated overnight at 4 degrees C and, after extensive
      washing, bound STA was quantitated by incubation with plasminogen (final
      concentration 0.5 microM) for 1 h at 37 degrees C, followed by determination of
      generated plasmin from the absorbance at 405 nm 10 min after addition of the
      chromogenic substrate S-2403 (final concentration 0.3 mM). Calibration curves
      constructed with natural (STAN) or recombinant (STAR) STA were linear between
      approximately 1 and 10 nM, with a lower detection limit of < or = 1 nM in buffer
      and in plasma of the human, baboon or hamster. Following bolus injection of STAR
      in hamsters, the disposition rate of STAR activity from plasma, determined with
      the BIA correlated very well (r = 0.98) with that of STAR-related antigen
      determined by ELISA, indicating that STAR is cleared in a functionally active
      form. The initial half-life was about 2 min, as determined with both methods.
      Following continuous intravenous infusion over 1 h in baboons, the plasma
      clearance of STAR activity, determined from the infusion rate and the steady
      state plasma level of STAR activity, ranged between 45 and 62 ml/min for doses of
      STAR between 0.063 and 0.250 mg/kg.

PMID- 8259556
TI  - Molecular conversions of recombinant staphylokinase during plasminogen activation
      in purified systems and in human plasma.
AB  - Recombinant staphylokinase (STAR) is produced as a 136 amino acid protein with
      NH2-terminal sequence Ser-Ser-Ser (mature STAR, HMW-STAR), which may be converted
      to lower molecular weight forms (LMW-STAR) by removal of the first six residues
      (yielding STAR-delta 6 with NH2-terminal Gly-Lys-Tyr-) or the first ten residues
      (yielding STAR-delta 10 with NH2-terminal Lys-Gly-Asp-). In the present study the
      occurrence and effects of these conversions during plasminogen activation by HMW
      STAR were studied in purified systems and in human plasma. In stoichiometric
      mixtures of HMW-STAR and native human plasminogen (Glu-plasminogen), rapid and
      quantitative conversion of HMW-STAR to LMW-STAR occurred, concomitant with
      exposure of the active site in the plasmin-STAR complex. NH2-terminal amino acid
      sequence analysis revealed the sequence Lys-Gly-Asp- in addition to the known
      sequences of the Lys-plasmin chains, identifying STAR-delta 10 as the derivative
      generated from HMW-STAR. In mixtures of catalytic amount of HMW-STAR and human
      plasminogen, plasmin generation occurred progressively, following an initial lag
      phase, during which HMW-STAR was converted to LMW-STAR. Plasmin-mediated
      conversion of HMW-STAR to LMW-STAR obeyed Michaelis-Menten kinetics with Km = 3.6
      microM and k2 = 0.38 s-1. The specific clot lysis activities of HMW-STAR (122,000
      +/- 8,000 units/mg) and LMW-STAR (129,000 +/- 8,000 units/mg) were
      indistinguishable. In an in vitro system consisting of a 60 microliters plasma
      clot submerged in 250 microliters plasma, 80% clot lysis within 1 h was obtained
      with 70 nM HMW-STAR.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259557
TI  - The platelet-stimulating effect of adrenaline through alpha 2-adrenergic
      receptors requires simultaneous activation by a true stimulatory platelet
      agonist. Evidence that adrenaline per se does not induce human platelet
      activation in vitro.
AB  - The stimulating effect of adrenaline on human platelet phospholipase C (PLC)
      activation and responses in vitro (shape change, aggregation and dense granule
      secretion) was investigated with respect to its dependence on exogenously added
      agonists. All experiments were performed with human gel-filtered platelets
      pretreated with acetylsalicylic acid to prevent endogenous stimulation by the
      arachidonate pathway. (1) Preliminary experiments demonstrated the presence of
      trace amounts of extracellular ADP (0.05-0.58 microM) in non-stimulated platelet
      suspensions; ADP was effectively converted to ATP by the enzyme system creatine
      phosphate (CP)/creatine phosphokinase (CPK). (2) The adrenaline-induced optical
      aggregation and single particle (platelet) disappearance in the presence of trace
      amounts of ADP were almost abolished by the ADP-scavenger system CP/CPK. (3) The
      response of CP/CPK-treated thrombin- or platelet-activating factor (PAF)
      stimulated platelets was markedly increased by a subsequent addition of
      adrenaline. When hirudin or BN 50726 was added just prior to adrenaline to
      terminate the activation by thrombin or PAF, respectively, the stimulating effect
      of adrenaline was also abolished. (4) CP/CPK-treated, PAF-stimulated platelets
      rapidly developed decreased responsiveness to a subsequent addition of PAF. When
      adrenaline was added instead of a second addition of PAF, the stimulating effect
      of adrenaline was gradually decreased and prevented in parallel with the
      homologous desensitization of PAF. (5) The weak platelet agonist serotonin by
      itself induced only shape change in CP/CPK-treated platelets. Adrenaline failed
      to enhance the extent of this serotonin-induced platelet activation. (6) These
      results strongly suggest that adrenaline per se is not a platelet agonist in
      vitro but acts to enhance the stimulation induced by true agonists.

PMID- 8259558
TI  - Platelet aggregation on extracellular matrix: effect of a recombinant GPIb
      binding fragment of von Willebrand factor.
AB  - Platelets in whole blood incubated on extracellular matrix (ECM) produced by
      bovine corneal endothelial cells under oscillatory flow conditions demonstrate
      extensive aggregate formation. Since both platelet-subendothelium and platelet
      platelet interactions are mediated by von Willebrand factor (vWF), we used this
      system to examine the effect of a recombinant GPIb-binding fragment of vWF
      (designated RG12986), comprising residues 445-733 of the native vWF subunit, on
      platelet reactivity with ECM. The seven cysteines present in the RG12986 fragment
      were reduced and alkylated in order to achieve a monomeric conformation. The
      recombinant vWF fragment binds to unstimulated platelets in the absence of
      exogenous modulators. When added to platelet-rich plasma, it inhibits ristocetin
      induced platelet agglutination. Binding of 51Cr-labeled platelets in
      reconstituted whole blood to ECM was inhibited by RG12986 in a dose dependent and
      saturable manner, with IC50 of 4 microM and maximal inhibition (about 70%) at 6
      microM. Scanning electron microscope (SEM) analysis showed that addition of
      RG12986 to whole blood significantly inhibited platelet aggregation on ECM. The
      extent of inhibition observed with RG12986 at a final concentration of 4 microM
      was similar to that obtained with the cell adhesion peptide RGDS at the
      concentration of 0.1 mM. The ability of the RG12986 fragment to inhibit platelet
      aggregation on ECM is in agreement with the concept that blockade of vWF-GPIb
      interaction may inhibit further events leading to activation of the glycoprotein
      IIb/IIIa (GPIIb/IIIa) complex and subsequent thrombus formation.

PMID- 8259559
TI  - Some relations between light transmission changes and biochemical parameters of
      stored platelet packs.
AB  - In the present work a computerised method for continuous monitoring of light
      transmission through platelet packs was evaluated. On series (Series 1) of 50
      platelet concentrates was studied over a 5-day period, and thereafter the pH,
      extracellular lactate dehydrogenase (LDH) and platelet factor 4 (PF4) in the
      concentrates were determined. A second series (Series 2) of 52 concentrates was
      also monitored over 5 days, and thereafter the pH, extracellular LDH and
      intracellular concentrations of ATP, ADP and AMP were determined. 11 and 14 of
      the concentrates of Series 1 and 2, respectively, demonstrated long lasting
      transmission increases (> or = 3.0 days). In the total of 102 platelet
      concentrates 34 were observed to have late (< 1.0 day) or no transmission
      increase. It is concluded, that the present optical method identifies both a
      group of platelet concentrates having long lasting transmission increases and a
      group consisting of platelet concentrates having late or no transmission
      increase. Compared to the latter concentrates preparations with long lasting
      transmission changes demonstrated significant biochemical alterations. These
      observations could be applicable in the quality control of platelet concentrates.

PMID- 8259560
TI  - Platelet aggregation and fibrinogen binding in human, rhesus monkey, guinea-pig,
      hamster and rat blood: activation by ADP and a thrombin receptor peptide and
      inhibition by glycoprotein IIb/IIIa antagonists.
AB  - Platelet aggregation and fibrinogen binding in whole blood, induced either by ADP
      or by a 14 amino acid peptide mimicking an N-terminal region of the platelet
      thrombin receptor (TRP, thrombin receptor activating peptide), have been studied
      with blood from different species. Aggregation was assessed by counting the
      number of single platelets in blood before und after addition of the agonist with
      an automated cell counter. Both ADP (0.02-0.5 microM) and TRP (1-10 microM) were
      found to be potent agonists of platelet aggregation in human, rhesus monkey and
      guinea-pig blood, causing a near-maximal aggregatory response within 2 min of
      agonist addition. In contrast, hamster and rat platelets were much less
      responsive to both ADP and TRP in terms of the whole blood aggregation.
      Echistatin, RGDW and a synthetic glycoprotein (GP) IIb/IIIa antagonist, Ro 43
      8857, inhibited fibrinogen binding to purified immobilized human GP-IIb/IIIa with
      IC50's of 1.6, 88 and 11.4 nM, respectively. In whole human blood, the respective
      IC50's (as determined by flow cytometric analysis of platelet fibrinogen binding)
      were 4.4, 1700 and 29.5 nM. The affinities of these three compounds for
      inhibiting fibrinogen binding in whole blood from rhesus monkeys and guinea-pigs
      were similar to the affinities for human platelets, but with rat blood
      echistatin, RGDW and Ro 43-8857 were all around 100-fold less potent. Ro 43-8857
      was a potent inhibitor of ADP- or TRP-induced platelet aggregation in human,
      rhesus monkey and guinea-pig whole blood (IC50 of 69-320 nM) but was much less
      active in hamster blood.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259561
TI  - Guidelines for clotting studies in cancer patients. For the Scientific and
      Standardization Committee of the Subcommittee on Haemostasis and Malignancy
      International Society of Thrombosis and Haemostasis.

PMID- 8259562
TI  - Beta 2-glycoprotein I and antiphospholipid antibodies assays: are we running
      appropriate sample-blanks?

PMID- 8259563
TI  - No evidence of platelet activation in obesity.

PMID- 8259564
TI  - Activation of fibrinolysis with the protease from dermatophagoides farinae.

PMID- 8259565
TI  - International survey of patients with von Willebrand disease and angiodysplasia.

PMID- 8259566
TI  - [Incidentaloma].

PMID- 8259567
TI  - [Significance of knowledge of medication after discharge--is there any cure?].

PMID- 8259568
TI  - [Cholera in Norway?].

PMID- 8259569
TI  - [Do patients know enough about their medication? A questionnaire among cardiac
      patients discharged from 5 Norwegian hospitals].
AB  - Information to patients on drugs is varied and often inadequate. This was
      demonstrated by a questionnaire answered by 173 patients after discharge from
      five Norwegian hospitals. The effects/indications were known by the patients for
      66% of the drugs. The daily dosage and dosage regimen were also known for more
      than 90% of the drugs, but possible side effects were unknown for more than 80%
      of the drugs. Knowledge of important interactions was low. 40% of the patients
      reported that the time alloted for information on drugs was insufficient, and 25%
      had many unanswered questions concerning drugs after discharge. This
      investigation shows that either the information on drugs from health care
      professionals to patients is insufficient, or that patients are incapable of
      absorbing and understanding the information provided. Hospitals should improve
      their drug related counselling service to patients at discharge.

PMID- 8259570
TI  - [Severe gastroenteritis after domestic infection with Vibrio cholerae non-O1].
AB  - Vibrio cholerae non-O1 has previously been isolated only occasionally in Norway
      from patients infected abroad. This report describes the clinical course in two
      patients who were domestically infected with V. cholerae non-O1. In one case,
      contaminated seafood, i.e. crab, was the probable source of infection. Both
      patients displayed a cholera-like type of illness, with severe diarrhoea and
      electrolyte disturbances. It is recommended that Norwegian laboratories be
      prepared to isolate vibrios also in domestically infected cases when watery
      diarrhoea is present.

PMID- 8259571
TI  - [Typhoid fever].
AB  - The epidemiology, clinical presentation, diagnosis and treatment of typhoid fever
      has been studied retrospectively in 50 hospitalized patients. Typhoid fever is
      increasing in Norway, owing to more travel, especially by immigrants visiting
      their home countries. Among 50 patients admitted to hospital for typhoid, we
      found no fatal complications. Fever was a main symptom, and 13 of the 50 patients
      had additional concomitant infections. The standard treatment was chloramphenicol
      for 14 days. In 1990 and 1991, however, most cases were caused by multi-resistant
      strains of Salmonella typhi. The adults were therefore treated with ciprofloxacin
      and the children with third generation cephalosporins. All the multiresistant
      infections had been contracted in Pakistan or India. There were no secondary
      cases among the more than 214 family contacts in the 47 families involved. The
      increase in resistant strains of typhoid fever may affect future treatment and
      control strategies.

PMID- 8259572
TI  - [Outbreak of typhoid fever in a family].
AB  - We describe a small epidemic of typhoid fever in a family who came originally
      from Pakistan. In 1992 six members (mother and five children) of a family of ten
      were admitted to our department with typhoid fever within a nine-day period. The
      index case was an 18 months old girl who had been hospitalized and treated
      elsewhere for typhoid fever. Two weeks after completing antibiotic treatment she
      was admitted to our hospital with a relapse. The source of her first infection is
      unknown. The rapid spread of typhoid fever in the family was most likely due to
      insufficient hygienic precautions and inadequate antibiotic treatment of the
      index case. Several coexisting factors such as poor housing conditions and
      cultural barriers may also have influenced the outcome. There is obviously a need
      for strict guidelines and proper coordination of treatment and follow-up of this
      and other similar contagious diseases.

PMID- 8259573
TI  - [Cor triatriatum with atrial fibrillation as initial symptom in adults].
AB  - Cor triatriatum is a rare congenital heart disease. In its classic form its
      consists of a fibromuscular perforated membrane which divides the left atrium and
      obstructs blood flow from pulmonary veins to mitral orifice. Clinical symptoms
      and signs resemble those of mitral stenosis. Traditionally cor triatriatum was
      encountered most often in infancy and childhood. We describe the case of a young
      man with cor triatriatum and atrial fibrillation, with syncope. He was operated
      on with total resection of the obstructing membrane. Modern echocardiography has
      made diagnosis more easy. Thus, an increasing number of cases of cor triatriatum
      are diagnosed in adults with few or no symptoms. Symptoms, diagnosis and
      treatment are discussed, with emphasis on these patients.

PMID- 8259574
TI  - [Invagination in children. New diagnostic and therapeutic aspects].
AB  - Based on the literature and our own experience, we recommend ultrasound
      examination as a routine in infants and small children with acute abdominal pain.
      If a pseudotumour is diagnosed, with suspicion of an intussusception, we verify
      the diagnosis by an air enema, and also use this for treatment under the
      surveillance of fluoroscopy and a conventional blood pressure manometer. The
      results are encouraging.

PMID- 8259575
TI  - [Wanderings through ancient medicine].
AB  - The character of ancient medicine depends on the concept of nature in ancient
      science. The development of a rational medical science was part of the historical
      emancipation of reason from magic and mythology. The great difference between
      ancient and modern medicine concerns the normative idea of nature in ancient
      thought versus the mechanical one in modern technology. The article mentions many
      special features of ancient medicine based on the notion of human nature and
      nature in general.

PMID- 8259576
TI  - [Life is short, art is long... Ancient medicine and philosophy].
AB  - For more than 2000 years, nothing has had so great an influence on western
      medicine as the Hippocratic writings of Aristotle and Galen. However, the legacy
      from these writings tends to be ambiguous, and two-fold. Some of them are clearly
      empirical, and make no attempt to philosophize about ultimate or proximate causes
      of disease. These are generally regarded as "genuinely Hippocratic". Other
      writings are dogmatic (rationalistic), and try to explain health and disease on
      the basis of pre-conceived ideas of the four humours of the human body. This
      distinction between empiricists and dogmaticians can be traced through Alexandria
      and Rome to modern times. The doctrine of the four humours does not seem to have
      had a beneficial effect on medical practice in Ancient Greece and Rome.

PMID- 8259577
TI  - [Vitamin A and toxicity. Should pregnant women and small children reduce their
      intake of liver products and vitamin A?].
AB  - It has been recognized for many years that high doses of vitamin A-metabolites
      may be teratogenic. Recently, it was found that the content of vitamin A in liver
      and liver products was much higher than the value prescribed in dietary tables.
      Thus, in many countries, health personnel advised pregnant women to reduce their
      intake of liver and liver products. Officials in Norway, however, have not given
      similar advice to Norwegian women. The background for this point of view is
      discussed in the present paper.

PMID- 8259578
TI  - [Physicians as leaders. Evaluation of a leadership training program for
      physicians (Medled)].
AB  - In September 1990, 40 doctors started a two year management training programme
      consisting of six one week courses organised by the Norwegian Medical
      Association. The programme was evaluated, and this article presents the results
      of two of the methods, used for evaluation: the first an interview with 12
      participants, and the second a questionnaire answered by participants, colleagues
      at the same department and colleagues at other hospitals (a control group) before
      and after the course. Compared with colleagues from the same department and from
      the control group the participants had changed their attitude towards important
      questions of management. They had become more concerned about the importance of
      motivating the staff, that the department should give priority to the hospital's
      objectives in preference to own interests, and that the ultimate responsibility
      for the department should reside in one person and this person should be a doctor
      with a relevant specialty. The results of the questionnaire survey are confirmed
      by the results of the interviews. In addition the results of the interviews
      suggest that, during the management training programme, the participants had
      changed from an individual-oriented to a more group-oriented style of management.

PMID- 8259579
TI  - [Hyperbaric oxygen therapy in the management of poisoning].

PMID- 8259580
TI  - [Transportation of sick newborn infants].

PMID- 8259581
TI  - [Registration of genetic information].

PMID- 8259583
TI  - [Disloyal behavior towards one's colleagues when alcohol abuse is suspected].

PMID- 8259582
TI  - [Radius fractures in general practice].

PMID- 8259584
TI  - [Africa's interest on debts is a catastrophe for the health--will the Medical
      Society sell by auction?].

PMID- 8259585
TI  - [The health care reform plan in the USA].

PMID- 8259586
TI  - [Soma and psyche in a Darwinistic perspective].

PMID- 8259587
TI  - Wound healing process in the portio vaginalis uteri after CO2-laser treatment.
AB  - In order to determine the would healing process in the portio vaginalis uteri,
      3[H]-thymidine incorporation and hydroxyproline concentration in the granulation
      tissue were measured histochemically after CO2-laser treatment. As a result, the
      squamous epithelium showed the thymidine uptake in extended regions in the first
      week and in basel cell hyperplastic regions in the second week. The uptake was
      seen in the reserve cell hyperplastic regions of the epithelium from the 2nd
      week. Hydroxyproline concentration peaks mostly appeared within one week after
      the laser treatment. After cryosurgery, the peaks mostly appeared after two weeks
      or more. These results indicated that, the stromas and then the squamous and
      columnar epithelial cells in turn were regenerated after CO2-laser treatment, and
      that the regeneration occurred earlier after laser treatment than after
      cryosurgery.

PMID- 8259588
TI  - The auditory evoked middle-latency responses (MLRs): their normative variation
      and generators.
AB  - Auditory evoked middle-latency responses (MLRs) to clicks were recorded in 68
      normal adults (ages from 21 to 59 year-old) at 16 scalp locations, all referred
      to a balanced non-cephalic reference. Both Na and Pa components were clearly
      demonstrated in all the subjects studied through the digital high-pass filtering.
      Both Na and Pa components were distributed dominantly over the frontal area in
      all subjects. The amplitudes of Na and Pa were significantly higher with binaural
      stimulation than with a monaural stimulation, and the existence of binaural
      interaction was also suggested. Binaural effect was more prominent in Pa than in
      Na component. When the data recorded from F3 and F4 electrodes were compared,
      most of F3/F4 amplitude ratios of Na and Pa were included between 0.7 and 1.5.
      The F3/F4 ratio should be useful indices for the diagnosis of excessive
      laterality. We also demonstrated gradual phase shifts of Na and Pa between the
      frontal and temporo-occipital area in about one-third of the records. This
      phenomenon strongly suggests that both Na and Pa components are derived from
      complex generators.

PMID- 8259589
TI  - Quantitative assessment of a change of hemosiderin deposition with age in splenic
      compartments of rats.
AB  - Hemosiderin deposition was quantitatively estimated in paraffin sections stained
      using Perls' iron reaction in the spleens of untreated male rats aged from 0 to
      28 months. Hemosiderin was deposited in the periarteriolar lymphocyte sheath
      (PALS), lymph follicles, and marginal zone, as well as in the red pulp which was
      the main compartment of hemosiderin deposition. Special attention was paid to the
      PALS and marginal zone. Marked hemosiderin deposition was evident from 4 months,
      although only few hemosiderin-laden macrophages appeared in the first 3 months.
      Hemosiderin deposition peaked at 12 months in the red pulp and at 20 months in
      the white pulp and marginal zone. The deposition in the white pulp and marginal
      zone was about 1/9 to 1/4 of that in the red pulp. A few hemosiderin-laden
      macrophages were found in the lymph follicles after 2 months. In the periarterial
      region of the splenic hilus, deposition of hemosiderin granules was observed even
      at 1 month when there was little hemosiderin deposition elsewhere. Since no
      arteries open there, the presence of hemosiderin-laden macrophages in the PALS
      and lymph follicles suggested movement of some macrophages from the red pulp
      and/or the marginal zone. In addition, hemosiderin deposition in the PALS
      increased with age after it decreased in the other compartments.

PMID- 8259590
TI  - Limited adaptation in chronically hypertrophied hearts from aortic constricted
      rats: increased inhomogeneity in cross-sectional area of cardiomyocytes and
      intercapillary distance.
AB  - To study the sequential changes of myocardial structure in pressure-overloaded
      heart, rats were subjected to banding of ascending aorta at 8 weeks of age, and
      electron-microscopical morphometry was performed at weeks 1, 2, 4, 8, 16, and 24
      postoperatively. Not only was the cross-sectional area of cardiomyocyte greater
      in banded rats but the degree of inhomogeneity increased in correspondence with
      development of hypertrophy. Intercapillary distance was significantly longer in
      banded rats than in controls. In banded rats, the distance around larger-than
      normal cells (with a cross-sectional area exceeding 600 microns 2) was
      significantly longer than that around normal-sized cells (with a cross-sectional
      area under 600 microns 2) at 4, 16, and 24 weeks following surgery.
      Morphologically, intracellular capillaries were shown to develop; however, single
      or several necrotic cells were observed in 8- to 16-week banded rats and were
      attributed to acute ischemia. In 24-week banded rats, advanced interstitial
      fibrosis as well as collapsed intracellular capillaries were observed.

PMID- 8259591
TI  - The growth of mouse hybridoma cells between Peyer's patch lymphocyte and myeloma
      cell in the gastrointestinal tract. A model for human multiple lymphomatous
      polyposis of the gastrointestinal tract.
AB  - To elucidate the mechanism of multiple lesions in human primary lymphoma or
      multiple lymphomatous polyposis of the gastrointestinal tract, we developed a
      experimental model utilizing mouse hybridoma cells. Syngeneic mice were immunized
      with human hemoglobin via gastric intubation and a hybridoma clone (13c) between
      the Peyer's patch cell and mouse myeloma cell was obtained. The 13c cells were
      infused into normal syngeneic mice through a lateral tail vein. About 2 months
      after injection mice were sacrificed and their viscera were scrutinized
      histologically. All 11 mice receiving 13c showed multiple tumors at the colon,
      microscopic massive invasions at the small intestine, and scattered invasions at
      Peyer's patch, mesenteric lymph nodes and the spleen, exhibiting the similar
      distribution patterns as in human multiple lymphomatous polyposis of the
      gastrointestinal tract. ME-1 or MU-1 cells (hybridomas between P3 and mouse
      spleen cell) were distributed at the liver, spleen and paraaortic lymph nodes.
      Such migration patterns of 13c cells and their adherence to vessel walls suggest
      that multiple invasions may be lymphocyte homing receptor-mediated phenomena.

PMID- 8259592
TI  - Away from the madding crowds.

PMID- 8259593
TI  - Trends in transfusion-associated acquired immune deficiency syndrome in the
      United States, 1982 through 1991.
AB  - To evaluate the efficacy of measures for preventing the transmission of human
      immunodeficiency virus (HIV) by blood transfusion, trends in transfusion
      associated cases of acquired immune deficiency syndrome (AIDS) reported through
      June 1992 were analyzed. By year of transfusion, cases rose from 56 in 1978 to
      714 in 1984, dropped sharply to 288 in 1985 when screening of donated blood for
      HIV antibody began, and fell below 20 per year from 1986 through 1991.
      Reinvestigation of a sample of cases suggested that only one-fourth of those
      attributed in the trends analysis to post-1985 United States transfusions
      actually were due to that source. By year of AIDS diagnosis, cases climbed from
      14 in 1982 to 824 in 1987 and subsequently remained relatively level. Of cases
      diagnosed in 1991 with known transfusion dates, almost all resulted from
      transfusions received before 1986. Cases in persons aged > or = 65 years at
      diagnosis fell steeply after 1987, while those in persons aged 45 to 64 years
      leveled and those in persons aged 25 to 44 years continued to increase; this
      caused the median age to decrease from 59 in 1986 to 47 in 1991. Thus, screening
      and other measures have almost completely prevented transmission, but, because of
      infections acquired before screening began, many cases continue to be diagnosed
      among increasingly younger persons.

PMID- 8259594
TI  - Development of a colorimetric dosimeter for quality control of blood units and
      irradiators.
AB  - The development is reported of a reproducible colorimetric irradiation dosimeter
      that is easy to prepare as well as to interpret. Optimal chloroform, dithizone,
      and paraffin concentrations to produce a distinctive color change at > 1500 cGy
      (optimized for 3000 cGy) were determined by combining various concentrations of
      each component at 65 degrees C. The melted dosimetric material was poured into
      molds, allowed to solidify, and irradiated with doses ranging from 0 to 3000 cGy.
      Color change was evaluated visually and spectrophotometrically to determine
      reproducibility. Twenty-percent chloroform (wt/wt) and a dithizone concentration
      of 5.0 x 10(-5) M combined in paraffin (TP-2) produced optimal color change from
      pink to green after > 1500 cGy. The change was reproducible, and 50 individuals
      were able to distinguish between irradiated and nonirradiated dosimeters.
      Additionally, five of five of these individuals correctly ranked five dosimeters
      in order of increasing irradiation from 0 to 3000 cGy, in increments of 750 cGy.
      This dosimeter is easy to make and easy to read and may allow blood banks to show
      unit-by-unit quality assurance for irradiated blood components and quality
      control of the irradiator itself.

PMID- 8259595
TI  - A prospective microbiologic surveillance program to detect and prevent the
      transfusion of bacterially contaminated platelets.
AB  - After two patients received bacterially contaminated platelet transfusions, a
      prospective surveillance program was instituted to perform Gram staining and
      microbiologic culturing of platelets at the time of transfusion. In 12 months,
      3141 random-donor platelet pools (prepared from 14,481 units) and 2476 single
      donor apheresis units were cultured. All single-donor apheresis units were
      sterile, but 6 (0.19%) of the random-donor pools were found to be bacterially
      contaminated, with 1 unit of 5 in the pool being the source in each case.
      Contaminants were Staphylococcus epidermidis (4 cases), Bacillus cereus (1), and
      Staphylococcus aureus (1) at counts of 0.5 x 10(2) to 10(11) colony-forming units
      per mL in platelet pools and 10(3) to 10(13) colony-forming units per mL in
      source units. The contamination rate for units transfused at < or = 4 days
      (1.8/10,000) was significantly lower than that at 5 days (11.9/10,000; p < 0.05),
      as was the magnitude of contamination (p < 0.05). Use of the pretransfusion Gram
      stain on 4- and 5-day-old platelet pools was 100 percent sensitive (4/4 true
      positives) and 99.93 percent specific (1 false positive) in detecting
      contaminated pools. These data define the extent and magnitude of platelet
      bacterial contamination and demonstrate the efficacy of the pretransfusion Gram
      stain on platelet units stored for 4 and 5 days in preventing the transfusion of
      heavily contaminated units. It is concluded that the risk of platelet
      contamination is related to the duration of component storage.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8259596
TI  - Potential for transfusion-associated graft-versus-host disease due to apheresis
      platelets matched for HLA class I antigens.
AB  - Transfusion-associated graft-versus-host disease (TA-GVHD) has been reported in
      immunocompetent recipients of nonirradiated cellular blood components from donors
      who are homozygous for an HLA haplotype shared with the patient. In these cases,
      donor lymphocytes have no antigens foreign to the recipient, and this similarity
      in HLA antigens appears important for the development of TA-GVHD. Experience with
      65 patients receiving apheresis platelets matched for class I HLA antigens was
      reviewed to determine the incidence of such a transfusion among HLA-matched,
      unrelated donor-recipient pairs. In 5 percent of transfusions (31/673), the
      patient received lymphocytes from a donor exhibiting no antigens foreign to the
      recipient, but the patient had additional HLA-A or -B antigens not present on
      donor lymphocytes. Twenty-three percent (n = 15) of patients received at least
      one such transfusion. In addition, most patients were immunosuppressed as a
      result of their underlying disease or therapy, which may decrease the degree of
      antigen matching required to initiate TA-GVHD. Until the pathogenesis of this
      disease is better understood, it is recommended that the transfusion of an HLA
      matched cellular blood component be considered a risk factor for the development
      of TA-GVHD regardless of the patient's immune status, and that all such blood
      components be irradiated.

PMID- 8259597
TI  - Age dependency of ABO histo-blood group antibodies: reexamination of an old
      dogma.
AB  - Current textbooks for transfusion medicine state that anti-A and/or anti-B (anti
      A/B) agglutination titers--and thus the respective antibody concentrations--reach
      their maximum in individuals 5 to 10 years old and then gradually decline with
      the increasing age of the individual. This statement is largely based on a study
      by Thomsen and Kettel that dates to 1929. In the present article, ABO antibodies
      in sera of 175 healthy persons aged 61 to 97 years, as well as sera of 170
      newborn infants and children aged 0 to 17 years, were analyzed.
      Microhemagglutination tests were performed with all sera and complemented by ABO
      enzyme-linked immunosorbent assays to measure the immunoglobulin class (IgM, IgG,
      and IgA) of the anti-A/B. As in a previous study using sera of persons aged 20 to
      67 years, individual differences exceeded age-related changes for all variables.
      Median values of IgG and IgA anti-A/B were elevated in elderly persons of blood
      group O, whereas no significant changes were observed in other variables. In
      particular, the decrease in agglutination titers with the increasing age of the
      individuals was far less pronounced than previously described; even in sera of
      persons aged 90 to 97 years, median agglutination titers of 128 were found.
      Results in the sera of children confirm previously reported data that
      agglutination titers and IgM anti-A/B reached adult levels at the age of 5 to 10
      years.

PMID- 8259599
TI  - Treatment with a pure factor IX concentrate in a patient with moderate hemophilia
      B undergoing bilateral total hip replacement.
AB  - Recently, a pure factor IX concentrate, licensed in Sweden as Immunine, was
      prepared through ion exchange and hydrophobic chromotography. Virus inactivation
      included two steps of steam treatment. Reconstituted Immunine could be kept at
      room temperature for at least 7 days without any substantial loss of activity. A
      patient with moderate hemophilia B undergoing bilateral total hip replacement was
      continuously infused with Immunine by use of a pump. There were no bleeding
      complications or signs of thrombosis, and the operation markedly improved the
      patient's range of motion and quality of life.

PMID- 8259598
TI  - Production of modified crosslinked cell-free hemoglobin for human use: the role
      of quantitative determination of endotoxin contamination.
AB  - In vivo toxicity remains a major barrier to the successful use of cell-free
      hemoglobin (Hb) as an oxygen carrier in humans. Bacterial endotoxin
      (lipopolysaccharide, LPS) is known to contribute to the in vivo toxicity of Hb
      preparations, and the prevention of LPS contamination is a critical aspect of the
      effort to create an efficacious Hb blood substitute. Limulus amebocyte lysate
      assays for endotoxin were performed on multiple Hb samples from 26 independent
      production runs for the preparation of human crosslinked cell-free hemoglobin
      (alpha alpha Hb). High levels of LPS contamination (1- > 100 ng/mL) of alpha
      alpha Hb solutions were detected in multiple samples during many of the initial
      production runs. It was observed that LPS contamination of alpha alpha Hb
      solutions could occur at any step during the production sequence. Substantial
      enhancement by alpha alpha Hb of the biologic effects of LPS was demonstrated by
      two independent assays for endotoxin (the Limulus amebocyte lysate test and a
      mononuclear cell procoagulant assay), whereas LPS biologic activity was only
      slightly increased by human serum albumin and substantially diminished by IgG.
      These results suggest that the prevention of LPS-related toxicities in vivo may
      be more important to the clinical use of Hb solutions than to the use of other
      intravenous protein products. Therefore, it was encouraging to note that, with
      the careful monitoring for LPS in the production facility and in multiple samples
      during cell-free Hb production, sources of LPS contamination were recognized and
      the appropriate sites were made endotoxin-free.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259600
TI  - What statistics can and cannot do.

PMID- 8259601
TI  - White cell content in apheresis platelets.

PMID- 8259602
TI  - Treatment of refractoriness to platelet transfusion by protein A column therapy:
      the role of the IgG subclasses.

PMID- 8259603
TI  - Use of the milky sap from Calotropis gigantea as a proteolytic enzyme in blood
      group serology.

PMID- 8259604
TI  - Apheresis and ACE inhibitors.

PMID- 8259605
TI  - Monoclonal anti-B reagents and the acquired B phenotype.

PMID- 8259606
TI  - [Autoantibodies against phospholipids].

PMID- 8259607
TI  - [Translocation and multiple organ failure].
AB  - A review of bacterial translocation and multiple organ failure (MOF) is
      presented. Splanchnic ischaemia plays a central role in the development of MOF,
      but the exact mechanism of translocation is unclear. The concentration of
      endotoxins and bacteria in the gut is high. The critically ill patient is often
      treated with antibiotics with a broad antibacterial spectrum and overgrowth of
      Gram negative bacteria will take place in the gut favouring the translocation
      phenomenon. The regime of selective gut decontamination is discussed. Regional
      and systemic oxygen kinetics together with metabolic markers are important in
      detecting splanchnic ischaemia. Hepatic vein catheterisation and gastric mucosa
      pHi are discussed. The regional inflammation in the gut is often initiated by
      endotoxins, which stimulate the cytokines IL-1, IL-6 and TNF. Another important
      factor that can accentuate inflammation of the gut is reperfusion injury. A
      proposal for treatment of splanchnic ischaemia and translocation is discussed
      i.e.: optimizing central haemodynamic parameters, optimizing the regional
      microcirculation, treatment with antibodies to endotoxins, gut decontamination
      and early enteral nutrition. When splanchnic hypoperfusion is detected it cannot
      be ignored. It may be possible to correct the hypoperfusion with early
      gastrointestinal resuscitation and to thereby reduce the duration and mortality
      of MOF. The above mentioned suggestions are all very demanding of resources, but
      have to be considered in gut directed therapy.

PMID- 8259608
TI  - [Heroin-induced pulmonary edema].
AB  - Based on a case story and having examined the literature, we describe the
      incidence, symptoms, course, complications and treatment of the kind of pulmonary
      oedema that may arise in connection with acute heroin intoxication. A possible
      pathogenesis is also discussed. Heroin-induced pulmonary oedema is rather
      frequent and the mortality is high. It differs from cardiogenic pulmonary oedema
      at essential points. It is most likely due to an increased permeability of the
      lung capillaries. However, it is still unclarified whether this is caused by a
      toxic or an allergic reaction, or by hypoxia. The treatment is supportive, using
      a respirator and oxygen enriched breathing air until the hypoxia has been
      abolished, and support of the circulation with reasonable liquid supply and
      infusion of inotropic and vasoactive drugs.

PMID- 8259609
TI  - [The antiprogesterone preparation mifepristone (RU 486). Should this "abortion
      pill" be introduced in Denmark?].
AB  - The antiprogesterone mifepristone (RU 486) was synthesized in 1980 by Roussel
      Uclaf (Paris). Since 1982 several studies have examined the ability of the drug
      to interrupt early pregnancies. 600 mg of mifepristone given by mouth to pregnant
      women with an amenorrhea of less than 50 days will lead to vaginal bleeding in
      more than 97% of the cases. The bleeding will be followed by moderate
      (menstruation-like) pain, and complete abortion will occur in 75% of the cases. A
      success rate of 75% is not sufficient for clinical use. The treatment should
      therefore consist of a combination of mifepristone and prostaglandin. The
      prostaglandin can be administered either by i.m. injections or as a vaginal
      suppository given 38-48 hours after the patient has received 600 mg of
      mifepristone by mouth. Such a combination of mifepristone and prostaglandin
      results in a complete abortion rate of more than 95%. Pelvic inflammatory disease
      (P.I.D.) after these abortions is extremely rare (below 0.5%), and other serious
      side effects are also uncommon. We find that mifepristone in combination with
      prostaglandin should be offered to Danish women seeking abortion as an
      alternative to the traditional method of vacuum aspiration.

PMID- 8259610
TI  - [The PRP-D vaccination of Danish children. A study of immunogenicity of a
      Haemophilus influenzae type b vaccine coadministered with Di-Te-Pol to Danish
      children].
AB  - The aim of this study was to examine the immunogenicity of a Haemophilus
      influenzae type b (Hib) vaccine (PRP-D) in Danish children younger than 18 months
      of age, given at the same time as a diphtheria-, tetanus- and polio-vaccine at
      the age of five, six and 15 months. The study was carried out as a multicentre
      study, where 21 children were vaccinated by their general practitioners. Blood
      samples were drawn just before and four weeks after each of the three
      vaccinations and the concentration of Hib-antibodies were determined using an
      ELISA-technique. Before the first vaccination none of the 21 children had
      antibody levels above 1 microgram/ml, which is believed to be the level which
      provides long-lasting protection, whereas after the first, second and third
      vaccination respectively 24, 48 and 100% of the children had antibody levels
      above 1 microgram/ml. There were only mild and short-lived side effects. The PRP
      D vaccine given at the same time as Di-Te-Pol is safe, without serious side
      effects and immunogenic in Danish children.

PMID- 8259611
TI  - [Sterilization of women in Denmark in 1990].
AB  - Investigation of the techniques employed in sterilization of women in Denmark in
      1990 was undertaken and compared to an equivalent investigation done in 1985. A
      questionnaire was sent to all hospitals in Denmark, Greenland and the Faroe
      Islands. Among the departments returning the questionnaire and carrying out
      sterilization of women in 1990, 29 departments were specialized gynaecological
      departments, 31 were non-subspecialized surgical departments and five were
      medical/surgical departments. Laparoscopic sterilization was used in every
      specialized gynaecological department. The percentage of surgical departments
      using this method has increased from 41.3 in 1985 to 87.0 in 1990. In 1990,
      bipolar electrocoagulation and clip-technique were the most frequently employed
      laparoscopic methods. In 1985 it was bipolar electrocoagulation. Five departments
      are still using unipolar electrocoagulation. In 1990, hysteroscopy mainly took
      place in the western part of Denmark.

PMID- 8259612
TI  - [Laparatomy in patients aged 80 years and older. A prospective analysis of
      morbidity during 1 year in the county of Ringkobing].
AB  - All patients aged 80 years or more admitted to the departments of general surgery
      in Ringkobing county, Denmark, during one year were studied prospectively in
      order to investigate morbidity and mortality following laparotomy in this patient
      group. A laparotomy was performed in 94 patients (67% women), in 73% as emergency
      cases. More than half of the patients had important coexisting diseases, and in
      half of the patients the cause of laparotomy was malignant disease, mostly
      colorectal cancer, while perforated or bleeding ulcer, cholecystitis,
      appendicitis, diverticulitis and incarcerated hernias were the most common benign
      causes of laparotomy. Postoperative complications were seen in 43% of the
      patients with a total mortality rate of 22%, mostly due to cardiac problems.
      Coexisting disease and emergency operation significantly increased both morbidity
      and mortality, which varied from respectively 8% and 0% after elective laparotomy
      in patients without coexisting diseases to respectively 71% and 39% after
      emergency operations in patients with coexisting diseases. In conclusion,
      laparotomy carries a high risk in elderly patients, particularly in the emergency
      situation. Efforts must be made in these patients to correct and treat any
      coexisting medical disorder prior to surgery, and when possible to perform early
      surgery before an elective operation turns into an emergency problem. Also, the
      development of new surgical procedures with lower morbidity must be encouraged.

PMID- 8259613
TI  - [Spinal cord injuries caused by suicide attempts].
AB  - During 1965-1987 45 patients were admitted to the Rehabilitation Hospital in
      Hornbaek, Denmark because of spinal cord injury (SCI) due to suicide attempts.
      The proportion of traumatic SCI due to this cause increased significantly during
      the period: 1965-1974: 3.5%, 1975-1984: 8%, 1985-1987: 13%. The median age at
      injury was 31 years, and the female to male ratio 1.6. In 38 instances (84%), SCI
      was caused by jumps from buildings. At the time of the SCI 62% were unemployed or
      receiving an early pension; 60% were living without a partner; 62% had previously
      been admitted to psychiatric hospitals, and 31% had previously attempted suicide.
      A follow up study was conducted in 1988-1989. At follow up 11 patients had died,
      three from suicide. Of the 34 alive at follow up, seven had attempted suicide,
      and two reported suicidal thoughts; 71% were living without a partner, 44% had
      had a psychiatric admission since the SCI; and 56% were taking psychiatric
      medication.

PMID- 8259614
TI  - [Effects of reducing the number of general practitioners on call on the pattern
      of the use of ambulances and emergency services].
AB  - The aim of the study was to evaluate the effect of a reduction of the number of
      general practitioners on call on the use of ambulance emergency service. A
      prospective registration of all ambulance emergency activity in the county of
      Ringkobing over an eight week period was made before and after the reduction of
      the number of general practitioners on call, together with a 4 + 4 week
      prospective registration of persons who claimed that contact to the general
      practitioners service was impossible, therefore resulting in a contact to the
      emergency central or the accident and emergency department. The numbers of
      emergency calls and emergency ambulance services in the population were
      unchanged, but there was a significant reduction from 78.9% to 69.3% in the
      relative number of ambulance services resulting in an admission to hospital of
      the patient. The number of patients, who claimed that contact to the general
      practitioner service was impossible was unchanged. We conclude that a reduction
      of the number of general practitioners on call has resulted in a reduction in the
      relative number of ambulance services resulting in hospital admission of the
      patient, which suggests a decline in the threshold of the population for calling
      an ambulance.

PMID- 8259615
TI  - [Work and safety conditions in transportation of patients between hospitals in
      Denmark].
AB  - Questions on the safety and comfort for the staff on interhospital transports
      were put to assistant matrons of anaesthesiological wards in Denmark. The
      investigation shows that ambulances leave with unattached equipment on the floor
      or in the patient's bed and that the staff either sit without safety belts or
      stand up beside the patient during transport. The ambulance interior is organized
      in such a way that the staff's working positions are negatively affected.

PMID- 8259616
TI  - [Delays in admissions for observation in suspected acute myocardial infarction].
AB  - One hundred and fifty-three patients hospitalized for observation and treatment
      of suspected acute myocardial infarction (AMI) were studied. The time delay from
      debut of symptoms until the decision was taken as to whether the patient was a
      candidate for treatment with thrombolysis or not was registered. The decision was
      made within four hours for 55.5% of the patients, and for 81.0% the decision was
      made within 12 hours of debut of symptoms. In all, 47 (30.1%) of the patients
      were treated with thrombolysis. Fifty-six (36.6%) of the patients had an AMI or
      unstable angina pectoris, and 39 (69.6%) were treated with thrombolysis.
      Seventeen patients with AMI did not receive the treatment, and for one of these
      the only reason for not receiving thrombolysis was a time delay longer than 12
      hours. The median time for patient delay was 60 minutes, doctors' delay 39
      minutes, and transport delay 29 min. At the hospital the first ECG was done 14
      minutes after arrival, and the decision about whether to treat with thrombolysis
      or not was taken 25 minutes after arrival. It is still possible to diminish the
      time delays for patients suspected of AMI. The longest delay is due to the
      patient, and public education is needed to minimize patient delay. Doctors are
      recommended to refer patients suspected of AMI directly to the hospital, omitting
      a delaying visit to the patient.

PMID- 8259618
TI  - [Fatal transmural colitis caused by Entamoeba histolytica. Differential diagnosis
      of chronic inflammatory bowel disease and colon cancer].
AB  - Perforation of the colon is a rare but frequently fatal complication of
      amoebiasis. We report a case of a 53 year-old male, with no history of travel
      abroad, who was admitted to hospital with haematochezia. A tumor of the rectum
      was diagnosed clinically. Due to acute intestinal obstruction, laparotomy was
      performed, revealing multiple perforations of the large bowel and severe
      peritonitis leading to subtotal colectomy. The histological examinations revealed
      transmural amoebic colitis. The patient died due to multi-organ failure.

PMID- 8259617
TI  - [Antiphospholipid antibodies and occlusive vascular disease].
AB  - The antiphospholipid syndrome is characterized by venous and/or arterial
      thrombosis, recurrent foetal loss, thrombocytopenia and the presence of
      antiphospholipid antibodies. This study presents three case reports, which
      emphasize the multiform clinical features of the syndrome: one case of
      uncomplicated myocardial infarction in childhood and two prolonged, clinically
      elusive case histories, both with fatal outcome due to acute, multifocal, non
      inflammatory vascular occlusion. It is important to distinguish between this
      syndrome and various vasculitis syndromes, although consensus on therapy for the
      antiphospholipid syndrome has not yet been achieved.

PMID- 8259619
TI  - [Deliveries in Denmark in 1991].

PMID- 8259620
TI  - [NO-NO-NO].

PMID- 8259621
TI  - [MMR-vaccinations and prevention of fatal cases].

PMID- 8259622
TI  - [Risk of HIV infection in health care].

PMID- 8259623
TI  - [Exposure to blood and risk of infection among health personnel].
AB  - Health care workers, especially surgeons, are frequently exposed to blood. Most
      blood exposures are not reported. Blood exposures involve risk of contracting
      serious infectious diseases like HIV, hepatitis B and hepatitis C. Fifty-four
      cases of occupational transmission of HIV-virus have been reported world wide.
      Occupational HIV-infection has not been reported in Denmark. Hepatitis B
      infection can be prevented by vaccination, but there is no effective drug or
      vaccine to prevent infection with hepatitis C and HIV-virus. Thus, the prevention
      of occupationally transmitted infections should concentrate on the prevention of
      blood exposures. Further studies on occupational blood exposure among Danish
      health care workers are needed.

PMID- 8259624
TI  - [Occupational blood exposure among personnel employed in a department of
      infectious diseases. 1. Frequency and reporting].
AB  - We investigated the frequency and reporting rate of occupational blood exposure
      among formerly and presently employed medical staff in a Department of Infectious
      Diseases (DID) from 1987-1991, the department has a high prevalence of HIV
      positive patients. Subjects were asked to complete an anonymous questionnaire
      describing occupational percutaneous (PCE) and mucocutaneous (MCE) blood exposure
      experienced during their employment at the DID. One hundred and thirty-five out
      of 168 (80%) subjects responded. Forty-five subjects described 37 PCE and 15 MCE.
      Forty-four (85%) of the exposures involved HIV-positive blood and six (11.5%)
      involved blood from a patient with hepatitis B. Incidence rates of PCE and MCE
      per year (PY) were: A) Interns and residents: 0.51 PCE/PY and 0.17 MCE/PY. B):
      Senior residents and senior physicians 0.13 PCE/PY and 0.21 MCE/PY. C) Registered
      nurses 0.11 PCE/PY and 0.03 MCE/PY. D) Nursing assistants 0.09 PCE/PY and 0.11
      MCE/PY. Sixty-five percent of PCE and 13% of MCE were reported to the security
      representative. The major reason for not reporting was that the subject found it
      unnecessary. We conclude that medical personnel, especially interns and
      residents, employed at clinics of infectious diseases have a real and serious
      risk of being exposed to infectious blood. The importance of reporting needs to
      be stressed.

PMID- 8259625
TI  - [Occupational exposure to blood among personnel employed in a department of
      infectious diseases. 2. Accidental mechanisms and protective devices].
AB  - We investigated exposure mechanisms of mucocutaneous (MCE) and percutaneous (PCE)
      blood exposures and compliance with universal precautions among all formerly and
      presently employed medical staff from 1987 to 1991 in a Danish Department of
      Infectious Diseases. All subjects were asked to complete an anonymous
      questionnaire. One hundred and thirty-five out of 168 (80%) subjects responded.
      Thirty-seven PCE and 15 MCE were described. More than 50% of PCE happened during
      procedures without specific reasons or were caused by unexpected patient
      movement, while only one PCE was caused by recapping. Thirty-five percent of PCE
      happened during drawing of venous blood samples. Compliance with usage of gloves
      was high (70-100%), depending on the procedure, and 72% of the subjects claimed
      to have sufficient knowledge of the risk of blood exposures and how to prevent
      it. Still, 11 (73%) out of 15 MCE might have been prevented by appropriate use of
      protective barriers. To reduce the frequency of blood exposure further the
      development of safer instruments and continuous education in safer techniques and
      usage of protective barriers are of major importance.

PMID- 8259626
TI  - [Facial mask--effective protection against blood spattering].
AB  - The protective effect of a see-through face visor was evaluated in four different
      types of operation. In a clinical trial, the visor was used 150 times by eight
      different surgeons, and the number of blood spatters, type of operation and blood
      loss was registered. There was no correlation between the size of the blood loss
      and the number of blood spatters. At caesarean section, a median of four blood
      spatters per operation was found on the visor. At the other three types of
      operation (hysterectomy, operation for vaginal prolapse and episiotomy) the
      median was one blood spatter per operation. The area surrounding the eye
      constituted three percent of the visor's area. We thus found the risk of getting
      a blood spatter in the area of the eye at caesarean section to be four percent
      (95% confidence limits 0.1-20.4). In conclusion, we found the face visor offered
      good protection against blood spatters.

PMID- 8259627
TI  - [Diabetic neuropathy: prevention and treatment].
AB  - Considerable progress has been made regarding symptomatic treatment of diabetic
      neuropathy. Apart from causal treatment (optimising metabolic control) a number
      of treatment modalities are now available for symptomatic diabetic neuropathy.
      The principles of symptomatic treatment depend very much upon which area of
      innervation is primarily affected. The optimal treatment of symptomatic diabetic
      neuropathy often requires the intervention of several clinical and paraclinical
      subspecialties.

PMID- 8259628
TI  - [Dimethicone in lactulose-induced dyspepsia. Effect on H2 production and
      symptoms].
AB  - The results of studies of the effect of simethicone on abdominal gas-related
      symptoms have been contradictory. In a randomized, double-blind, cross-over
      study, ten healthy volunteers were given 30 g lactulose and 600 mg simethicone or
      placebo. End-expiratory breath samples were collected and analyzed for H2, and
      gastrointestinal symptoms registered. There were no differences in biochemical
      parameters or symptom score between simethicone and placebo. In contrast to
      previous studies, we used a sufficiently large dose of lactulose to produce
      gastrointestinal symptoms, a higher dose of simethicone and placebo tablets
      containing the same additives as the simethicone tablets. There was no
      demonstrable effect of simethicone on symptoms or intestinal gas production
      caused by carbohydrate malabsorption.

PMID- 8259629
TI  - [Cardiovascular risk factors in snorers. The Copenhagen Male Study].
AB  - Former studies on the association between snoring and cardiovascular disease
      (CVD) have only partly taken established CVD risk factors into consideration. In
      the Copenhagen Male Study, 3323 men aged 54-74 years were classified according to
      self-reported snoring habits. Eleven CVD risk factors were examined. The
      prevalence of snoring decreased with age, with a 50% higher frequency of snorers
      in the youngest quintile than in the oldest, p < 0.00001. Snoring, age adjusted,
      was positively associated with tobacco smoking, p < 0.001, alcohol consumption p
      < 0.0001, body mass index (BMI), p < 0.0001, serum triglyceride level, p < 0.01,
      systolic blood pressure, p < 0.05 and diastolic blood pressure, p = 0.07. Snorers
      were less physically active in leisure time than others, p < 0.01. The
      association between self-reported snoring and blood pressure disappeared when
      other factors, including BMI, were taken into consideration. No significant
      associations were found between snoring and social class, snoring and low or high
      density lipoprotein, nor between snoring and hypertension. We conclude that
      snoring is associated with major cardiovascular risk factors. Accordingly, it is
      evident that in studies on snoring and cardiovascular disease, proper controlling
      for the influence of potential confounders is a sine qua non.

PMID- 8259630
TI  - [Markedly increasing incidence of apoplexy among men. A clinical, epidemiologic
      study of apoplexy incidence between 1972 and 1990 in the municipality of
      Frederiksberg].
AB  - The purpose of this study was to determine possible temporal changes of stroke
      incidence in a European community. All cases of first-ever stroke (n = 927) were
      prospectively recorded in the municipality of Frederiksberg, Denmark, in the two
      periods 1972-1974 and 1989-1990. Complete case ascertainment was ensured by
      registration of both hospitalized and nonhospitalized patients. Death
      certificates were also scrutinized. The annual stroke incidence rate per 1000
      increased by 18% from 2.6 in 1972-1974, to 3.1 in 1989-1990 (p < 0.01). This
      increase was due solely to a 42% increase in men, for whom stroke incidence rose
      from 2.1 to 3.0 (p < 0.0005). Incidence was unchanged in women, 3.0 and 3.1
      respectively. In the second study period 85% had CT or necropsy; 91% had cerebral
      infarction; 8% had intracerebral haemorrhage and 1% had subarachnoid haemorrhage.
      In a period when decline in stroke incidence has stopped in USA and has continued
      in Japan, a marked increase in stroke incidence in European men was observed.

PMID- 8259631
TI  - [Consequences of arthroscopic meniscal resection].
AB  - The functional and radiological consequences of arthroscopic meniscal resection
      were assessed in an 8.5 years follow up of 136 patients. Twenty three percent had
      undergone re-arthroscopy. Function related pain in the operated knee was reported
      by 44% of the patients. Radiological degenerative changes appeared in
      significantly more of the operated knees than in the knees not operated. The
      combination of varus knees and resection of the medial meniscus or valgus knees
      and lateral resection was associated with significantly more degenerative changes
      than after resection in knees with normal alignment. Resection of flap tears was
      associated with more re-operations and more function related knee pain than
      resection of bucket-handle lesions.

PMID- 8259632
TI  - [Cardiomyopathy caused by carnitine deficiency].
AB  - Primary carnitine deficiency often presents as progressive cardiomyopathy. It is
      due to a defect in the plasma membrane carnitine transport system that is
      normally present in heart, muscle and kidney. This system serves to maintain
      intracellular carnitine levels 20-50 times higher than plasma concentrations.
      Patients with this defect cannot maintain adequate carnitine levels in muscle
      tissue for fatty acid oxidation. One case of primary carnitine deficiency is
      described. Two siblings had died earlier probably due to the same disease. The
      eight month old boy presented with a common cold and cardiomyopathy. He was
      treated with digoxin and diuretics until the diagnosis was confirmed. The
      patient's uptake of carnitine in fibroblasts was extremely low, about 5% of the
      normal range. The father had about 50% reduction of carnitine uptake in
      fibroblasts, the mother showed no sign of impaired uptake. The boy was treated
      with oral carnitine, 100 mg/kg/day. There was a normal level of carnitine in
      serum after two months of treatment and the cardiomyopathy disappeared completely
      in one year. Primary carnitine deficiency is a treatable disorder and therefore
      skeletal muscle biopsy and blood chemistry should be performed in all children
      with undiagnosed cardiomyopathy. Treatment with oral carnitine must be initiated
      quickly to avoid sudden death.

PMID- 8259633
TI  - [Guillain-Barre syndrome in children treated with intravenous immunoglobulin].
AB  - The clinical course of subacute demyelinating polyneuropathy or Guillain-Barre
      syndrome (GBS) in adults is known to improve more rapidly and with fewer
      complications when treated with plasma exchange or intravenous immunoglobulin
      than supportive care alone. Recent results indicate the best improvement is found
      with intravenous immunoglobulin. In children little is known about the efficacy
      of intravenous immunoglobulin, though case reports seem to document effect. Three
      cases of GBS in children aged two, three and nine years, who all were treated
      with intravenous immunoglobulin 400 mg/kg/day for five days, are reported. There
      was marked clinical improvement during treatment in two children, the third child
      developed respiratory insufficiency needing artificial respiration during
      treatment, but improved rapidly after five days of intravenous immunoglobulin.

PMID- 8259634
TI  - [Honey: a potential wound-healing agent with antibacterial activity].

PMID- 8259635
TI  - [Drug costs].

PMID- 8259636
TI  - [Mercury manometers will not be prohibited].

PMID- 8259637
TI  - [Transport of nitrates and nitrites into the milk of dairy cows through the
      digestive system].
AB  - Increased nitrate concentrations in milk are not only dangerous to human health
      as the milk is the material for production of baby and infant food, but they
      cause also many problems in technological milk processing. The study was aimed at
      the transfer of nitrates and nitrites into milk of dairy cows following nitrate
      loading. An experiment included 6 dairy cows of the Slovakian Spotted breed at
      the Experimental Veterinary Centre at Zemplinska Teplica. Prior to start of the
      experiment samples of feedstuffs and feed water, milk were taken and examined for
      the presence of nitrates and nitrites. KNO3 in water solution was applied to
      selected dairy cows in two-week intervals in single peroral doses of 150; 75;
      37.5; 18.75 and 9.5 g two hours before evening milking. Nitrate and nitrite
      residue contents were studied in individual milk samples obtained from manual
      milking 2, 14, 26, 38 and 50 hours after application of appropriate KNO3 amount.
      Following the peroral application of KNO3 to dairy cows, a marked increase in
      nitrate content in milk appeared in dependence on applied KNO3 (Tab. I). Average
      value of residual nitrate in milk two hours after administration of 150 g of KNO3
      was 34.60 mg of NO3-/l. Increased levels of residual nitrate in milk were found
      also 38 hours after KNO3 application. Nitrate content in milk after 50 hours was
      almost identical with that that was determined in milk of experimental cows from
      morning milking on the day of administration of 150 g of KNO3, considered as the
      control samples. The values of residual nitrate exceeded 0.05 mg neither in
      single sample of NaNO2/l.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259638
TI  - [The role anaerobes in dermatitis digitalis et interdigitalis in cattle].
AB  - Altogether 52 tissue samples and swabs from the corium of the claw of diseased
      cattle were investigated. Microbiological examinations revealed the presence of
      11 strictly anaerobic bacterial strains that belonged to the species Peptococcus
      asacharolyticus, Pc. sacharolyticus, Peptostreptococcus anaerobius, Bacteroides
      asacharolyticus and B. melaninogenicus. The remaining isolates were classified as
      Bacteroides, Fusobacterium, Streptococcus and Clostridium. In the above-mentioned
      strains observations of their biochemical, morphological and enzymatic properties
      (Tab. I) were carried out. Their resistance to antibiotics was evaluated from the
      qualitative viewpoint (Tab. II). Capillary isotachophoresis was used to determine
      the amounts of volatile fatty acids that developed during glucose fermentation
      (Tab. III). In the single clinical samples the above-mentioned strains occurred
      as association of microorganism. The anaerobic genera Bacteroides and
      Fusobacterium were found in 52% of the samples (Bacteroides sp. and Fusobacterium
      sp. were recorded in 25% and 12% of the samples, respectively, whereas in 15% of
      the samples both species occurred). According to our results the etiology of
      dermatitis digitalis et interdigitalis is closely connected with the incidence of
      anaerobes. Of the latter, those belonging to the genera Bacteroides and
      Fusobacterium are of major importance.

PMID- 8259639
TI  - [Zinc, selenium and copper supplementation using rumen pellets and its effect on
      cellular and humoral responses in sheep].
AB  - The objective of the study was to test the effectiveness of Zn, Se and Cu
      supplementation through reticulum-rumen pellets and its effects on the rate of
      cellular and humoral reactions in sheep. An experiment included 12 lambing ewes
      of the Merino breed at the age of two years. Zn-containing pellets were applied
      via rumen to three lambing ewes at the end of November, Se pellets were applied
      to other three lambing ewes Cu pellets to other three ewes. Three lambing ewes
      were control. Blood samples were taken from the v. jugularis from all the
      investigated ewes before bolus administration, in month 1, 2, 3, 4, 6 and 7 after
      application. Zn, Se and Cu concentrations in the blood serum were determined by
      atomic absorption spectrophotometry. Immune reactions were evaluated from the
      concentrations of serum immunoglobulins (IgC), albumin (ALB), total proteins
      (TP), from phagocytic activity (PA), phagocytic index (PI), migration-inhibitory
      test (MIT) and determination of tetrazolium-reductase activity of phagocytes (INT
      test). In comparison with the starting values, the highest increase in zincemia
      (80%) was recorded in the lambing ewes administered zinc boluses as soon as in
      the 1st month after administration. A significant difference in Zn concentrations
      between the zinc-pellet group and the control animals was observed in the 1st
      month after administration (P < 0.01). An increase in Se concentrations in the
      blood serum was observed in the lambing ewes administered selenium boluses in the
      1st month after administration. Se content in the blood serum of the given group
      of ewes was highest at the end of observation (2.72 +/- 0.29 mumol/l). A
      statistically significant difference in Se content between the group of selenium
      bolus ewes and the control ewes was confirmed at a significance level P < 0.05 in
      the 1st and 2nd month of the experiment. Cu concentrations in the blood serum in
      the Cu-bolus ewes increased in the 1st month if compared with the starting
      values. The highest Cu concentration in the blood serum was recorded in the given
      group within month 4 to 7 of the experiment (16.53 +/- 2.72, or 21.23 +/- 4.40
      mumol/l). There were significant differences in cupremia between the Cu-pellet
      group of ewes and the control animals (P < 0.05). In comparison with the starting
      values, the highest increase in TP concentrations were determined in the Cu
      pellet ewes in the 4th, 6th, and 7th months. Albuminemia dynamics in the
      experimental animals and in the control group did not vary
      significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259640
TI  - [Lactate dehydrogenase isoenzymes in purebred sheep and rams].
AB  - In farm animals the questions of clinical and mainly heritable health receive
      increased attention. In this work the activity of the polymorphous system of
      lactate dehydrogenase was observed in some pure- and crossbred ewes and rams
      under field conditions. The isoenzyme of lactate dehydrogenase were separated on
      5.5% polyacrylamide gel as reported Dietz, Lubrano (1967). Age- and sex-related
      determinations of the isoenzyme spectrum of lactate dehydrogenase revealed
      increased LD3 activity in yearling ewes, and increased LD4 and LD5 activity in
      yearling rams (Tab. I). Significant differences of LD4 isoenzyme activity (P <
      0.05) were observed between the Stavropol Merino and the Stavropol Merino x
      Merino x Corriedale crossbreds (Tabs II and III). In the blood plasma of
      Stavropol Merino rams the following quantities of LD isoenzymes were determined:
      LD1 = 48.0 +/- 10.6%, LD2 = 12.1 +/- 5.2%, LD3 = 25.9 +/- 7.02%, LD4 = 4.0 +/-
      2.2% and LD5 = 10.0 +/- 3.5%. In the activity of some isoenzymes breed
      differences were recorded in 2-5-year-old ewes (Tabs IV and V). For LD1,
      significant differences (P < 0.01) were found between the Merino and Ascan Merino
      x Merino sheep breeds as well as between the Merino x Corriedale sheep and the
      crossbreds of Merino with a certain share of Lincoln. Differences in LD1 activity
      between Merino and Merino x Corriedale sheep as well as between the Ascan Merino
      and Merino crossbreds with a certain share of Lincoln were significant at the
      level of P < 0.02. For LD2, no significant differences were stated in the pure-
      and crossbred animals under examination.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259641
TI  - [Epizootiology and pathogenesis of avian mycobacteriosis in doves (Streptopelia
      sp.)].
AB  - The collared turtle-dove (Streptopelia decaocto) and the turtle dove are common
      synanthropic bird species. The collared turtle dove in particular comes to close
      contact with farm animals, including with tuberculosis-infected small poultry on
      farms. It can thus be infected by avian mycobacteria and to become their further
      source and disseminator. Elucidating the occurrence of avian mycobacteriosis in
      turtle we examined 218 specimens of the collared turtle-doves and 22 specimens of
      turtle-doves taken in habitats with different epidemiological setting. We found
      no pathomorphological tuberculous lesions and isolated no mycobacteria from
      organs or the contents of intestines in any of them, though we also examined
      turtles living near poultry farms infected with tuberculosis or near farms where
      avian tuberculin-positive cattle was reared. Under the same conditions we found
      repeatedly, e.g. in sparrows, both the tuberculous lesions and mycobacteria. The
      turtle dove can thus be considered as very resistant to avian mycobacteria and
      the occurrence of avian mycobacteriosis can be regarded as rather exceptional.
      The susceptibility of the collared turtle-dove to avian mycobacteria was verified
      also by experimental infections. After intramuscular infections of M. avium
      serotype 2 suspension, we demonstrated macroscopic tuberculosis lesions only in
      the site of inoculation from day 21 onwards. The histological lesions were found
      in the liver, spleen and bone marrow from day 28 after inoculation. However,
      mycobacteria were isolated from various organs and tissues as early as 12 days
      after inoculation. Attempts to demonstrate tuberculous lesions and to isolate
      mycobacteria from the intestines failed. No tuberculous lesions produced in
      turtle dove within the period of 122 days after peroral infection by food
      contaminated by TBC poultry livers and bacteriologically examined was negative
      too. After free contact between TBC poultry and turtle doves the sporadic
      histological TBC changes in liver were found after 180 days and in one case
      mycobacteria were isolated from the liver and muscle after 157 days. The transfer
      of M. avium from TBC infected turtle doves pigs and poultry was successful. After
      45 days of join contact among TBC turtle doves, healthy pigs and poultry in
      stables and after further stay of pigs and poultry in contaminated environment
      for additional 65 and 175 days, respectively. In the course of the experiment,
      105 days after its onset, marked reaction to avian tuberculin was demonstrated in
      one pig. Simultaneously with it, the TBC lesions in mandibular and mesenteric
      lymphatic glands were found. In one pig, mycobacteria were isolated from those
      suspectedly affected lymphatic glands.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8259642
TI  - [The black-headed gull (Larus ridibundus L.), a new host for Cryptosporidium
      baileyi (Apicomplexa: Cryptosporidiidae)].
AB  - Black-headed full (L. ridibundus L.) represents a new host of C. baileyi Current,
      Upton and Haynes, 1986. In 1991-1992 during the months of May-July six localities
      in three regions of the Czech Republic were studied by examining in total 264 not
      flying gull chicks (4-30 days of age), applying the methods after Pavlasek
      (1987a, b, 1991). Cryptosporidia were found in gulls in all localities and
      spontaneous infection during the period under study occurred in 27.5-100% of
      birds (Tab. II, Fig. 1). The size of oocysts was 6.2-6.4 by 4.8-5.8 microns with
      means of 6.4 by 4.9 microns. The oocyst index (width/length) was 0.75-0.93 with
      means of 0.77. C. baileyi infection was demonstrated in 22 out of 24 dead gull
      chicks submitted to autopsy. From two localities total 15 gulls were killed, the
      examination of which revealed oocyst occurring in masses in the fluid from
      cloacal washes. Asexual and sexual endogenous developmental stages, including C.
      baileyi oocysts, in all birds undergoing autopsy were localized in caudal part of
      colon (1-2 cm from opening into cloaca) and in the cloaca. Findings of
      cryptosporidia were very frequent, above all, in the bursa Fabricii. In two dead
      and six with snoring disease, subsequently killed gull chicks, respiratory form
      of infection was demonstrated with simultaneous proof of endogenous developmental
      stages including oocysts in smears of mucous epithelium of sinus infraorbitalis,
      larynx, trachea and bronchi using the Giemsa stain after fixation with absolute
      methanol. An experimental transmission of infection by isolates of C. baileyi
      oocysts from gulls to five 4-day chicks (Gallus gallus f. domestica) using the
      dosis of 5 x 10(5) oocysts/chick was successful. The prepatent period lasted 4
      days. On day 3 and 6 after infection two chicks died. The developmental stages of
      the protozoon were found in the lower part of colon, in cloaca and in bursa
      Fabricii. In chicks dead on day 6 after infection asexual stages of
      cryptosporidia were found in trachea and in bronchi. One chick survived the
      infection and excretion of oocyst (patent period) lasted 14 days. In this bird
      cloacal, bursal as well as respiratory form of C. baileyi infection was found.
      Control chicks were negative during the observation of 30 days. Oocysts from
      gulls do not lose their viability even after 8-month storage in the 2.5% solution
      of K2Cr2O7 at the temperature of 4 degrees C.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8259643
TI  - Mechanism of lymphocytic choriomeningitis virus entry into cells.
AB  - The path that the arenavirus lymphocytic choriomeningitis virus (LCMV) uses to
      enter rodent fibroblastic cell lines was dissected by infectivity and inhibition
      studies and immunoelectron microscopy. Lysosomotropic weak bases (chloroquine and
      ammonium chloride) and carboxylic ionophores (monensin and nigericin) inhibited
      virus entry, assessed as virus nucleoprotein expression at early times post
      infection, indicating that the entry process involved a pH-dependent fusion step
      in intracellular vesicles. That entry occurred in vesicles rather than by direct
      fusion of virions with the plasma membrane was confirmed by immunoelectron
      microscopy. The vesicles involved were large (150-300 nm diameter), smooth
      walled, and not associated with clathrin. Unlike classical phagocytosis, virus
      uptake in these vesicles was a microfilament-independent process, as it was not
      blocked by cytochalasins. LCMV entry into rodent fibroblast cell lines thus
      involves viropexis in large smooth-walled vesicles, followed by a pH-dependent
      fusion event inside the cell.

PMID- 8259644
TI  - Induction of rotavirus-specific cytotoxic T lymphocytes by vaccinia virus
      recombinants expressing individual rotavirus genes.
AB  - We determined the capacity of vaccinia virus recombinants expressing individual
      rotavirus genes to induce virus-specific cytotoxic T lymphocytes (CTLs) in mice.
      Mice were orally inoculated with vaccinia virus recombinants containing genes
      which encode rotavirus outer capsid proteins vp4 or vp7, single-shelled virus
      proteins vp1, vp2, or vp6, or rotavirus nonstructural proteins NS53, NS35, NS28,
      or NS26/NS12. We found that (i) the greatest frequencies of virus-specific CTLs
      were induced by vaccinia virus recombinants expressing vp7, (ii) transport of vp7
      beyond the endoplasmic reticulum was not necessary for induction of CTLs, (iii)
      recombinants expressing vp7 induced CTLs which reacted with different rotavirus
      serotypes, and (iv) CTLs were induced among both intestinal and nonintestinal
      lymphocytes after oral inoculation. These findings may be relevant to vaccine
      strategies which utilize vectors expressing individual rotavirus genes.

PMID- 8259645
TI  - Mutations in the nsP1 coding sequence of Sindbis virus which restrict viral
      replication in secondary cultures of chick embryo fibroblasts prepared from aged
      primary cultures.
AB  - SVMPA, a mutant of Sindbis virus (SV), which is able to replicate in Aedes
      albopictus cells treated with mycophenolic acid (MPA) or ribavirin, also has a
      host range phenotype. This phenotype is most clearly demonstrated by means of
      efficiency of plaquing (EOP) assays on secondary chick embryo fibroblasts (CEF)
      prepared from aged primary CEF. For example, in one experiment in which standard
      SV (SVSTD) had a relative EOP (EOP on primary CEF divided by EOP on secondary
      CEF) of 1.6 the corresponding value for SVMPA was 2340. The host restriction of
      SVMPA was also seen with similarly prepared secondary cultures of duck embryo
      fibroblasts, but not with established lines of quail cells. The finding that the
      accumulation of viral RNA was much lower in SVMPA-infected secondary CEF than in
      SVSTD-infected CEF indicated that the replication of SVMPA in these cultures was
      blocked at an early step. Revertants of SVMPA were isolated which were no longer
      host-restricted but had retained their resistance to MPA. Of the three mutations
      [nucleotide (nt) 120, 127, and 963] in the nsP1 coding sequence of SVMPA, which
      lead to amino acid changes, these revertants had retained the nt 127 and nt 963
      mutations but had lost the nt 120 mutation. This, along with earlier findings,
      indicated that only the nt 127 and nt 963 mutations are required for resistance
      to MPA. This result also associated the nt 120 mutation with the host restriction
      phenotype. In other experiments derivatives of pToto1101 (a plasmid from which
      infectious Sindbis virus RNA can be transcribed) were constructed by site
      directed mutagenesis and used to test the effect of specific mutations on the
      viral phenotype. Although we were unable to obtain viable virus with the nt 120
      mutation alone, virus with the nt 120 and nt 127 mutations was viable and host
      restricted. We suggest that the nt 120 mutation by itself is lethal and that the
      nt 127 mutation suppresses the lethal effect of the nt 120 mutation. The SVMPA
      mutation at nt 120, which is associated with the host range phenotype, changes
      Gln21 of nsP1 to Lys. When a more conservative change was engineered, i.e., to
      Asn, the virus was not host-restricted. Although the reason for the restriction
      of SVMPA replication in secondary CEF is not known, some possible explanations
      are discussed.

PMID- 8259646
TI  - Structural changes and functional control of the tick-borne encephalitis virus
      glycoprotein E by the heterodimeric association with protein prM.
AB  - We have used tick-borne encephalitis virus to study the involvement of acidic
      compartments during the entry and release phases of flavivirus infection and to
      elucidate the role of protein prM in immature virions. Elevation of the pH in
      acidic intracellular compartments by either bafilyomycin A1, a specific inhibitor
      of the vacuolar type H(+)-ATPase or by NH4Cl had a strong inhibitory effect
      during virus penetration and also prevented the cleavage of prM when added in the
      late phase of the viral life cycle. In the latter case the release of virus
      particles was not impaired. These immature (prM-containing) virions exhibited a
      20- to 50-fold lower specific infectivity and HA activity than mature virions and
      in contrast to these did not undergo low pH-triggered aggregation. The presence
      of prM also affected the binding of monoclonal antibodies to protein E,
      especially at sites which have been shown to undergo acid pH-induced
      conformational changes in mature virions. Crosslinking, solubilization, and
      sedimentation analyses revealed the existence of prM-E heterooligomeric
      complexes, suggesting that the function of prM is to protect protein E from
      undergoing the irreversible conformational changes in acidic compartments of the
      secretory pathway that are necessary for triggering fusion activity in the
      endosome during virus entry.

PMID- 8259647
TI  - A poxvirus protein with a RING zinc finger motif is of crucial importance for
      virulence.
AB  - The DNA sequence of a 2060-bp fragment from the left-hand end of the ectromelia
      (mousepox) virus genome was determined. Two genes were identified coding for 28
      kDa (p28) and 16 kDa (p16) proteins, both of which are disrupted in vaccinia
      virus but conserved in variola (smallpox) virus. p16 contains an N-terminal
      hydrophobic region and may be a membrane or secreted protein. p28 contains a
      C3HC4 (RING) zinc finger motif that has been found in a large family of proteins
      involved mostly in transcription regulation. p28 was expressed in bacteria and
      shown to bind Zn in vitro. Disruption of the p28 gene had no appreciable effect
      on the multiplication of the virus in cell culture but abolished its lethality
      for susceptible mice. The p28- mutant virus replicated to significantly lower
      titers than the wild-type virus in different organs of infected mice. It is
      proposed that the p28 gene is an important determinant of orthopoxvirus
      pathogenicity, and its product may positively or negatively regulate expression
      of host or viral gene(s) involved in virus-host interaction.

PMID- 8259648
TI  - Mother-to-baby transfer of humoral immunity against retrovirus-induced neurologic
      disorders and immunodeficiency.
AB  - Neonatal FVB/N mice inoculated with ts1, a temperature-sensitive mutant of
      Moloney murine leukemia virus TB, developed fatal immunodeficiencies and
      neurologic disorders. In this study, we tested the role of transfer of maternal
      humoral immunity in preventing ts1-induced disease syndrome in the neonatal mice.
      We compared the levels of protection provided through maternal antibodies both
      pre- and postnatally by separating infected neonatal mice into four different
      groups. The first group was born of and nursed by nonimmune mothers, the second
      was born of immune mothers but nursed by nonimmune mothers, the third was born of
      nonimmune mothers but nursed by immune mothers, and the fourth was born of and
      nursed by immune mothers. Our major findings are: (1) adult mice generate a
      strong antiviral antibody response; (2) maternal antibody is protective for the
      newborns and primarily transferred by breast milk; (3) virus titers were cleared
      in the periphery and the CNS of neonates nursing on immune mothers; and (4) the
      majority of antiviral antibody generated was specific for the gp70. These results
      indicate that humoral immunity can be passed efficiently from mother to baby
      through breast milk and can provide strong protection against neurotropic
      retrovirus.

PMID- 8259649
TI  - Cloning and expression of the nucleocapsid gene of virulent Kabete O strain of
      rinderpest virus in baculovirus: use in differential diagnosis between vaccinated
      and infected animals.
AB  - Rinderpest (RP) is a viral disease of ruminants with > 95% morbidity and
      mortality. We have cloned the cDNA of the nucleocapsid (N) gene of the virulent
      Kabete O strain of rinderpest virus (RPVK) and compared its nucleotide and
      deduced amino acid sequences with those of the N genes of the lapinized strain of
      rinderpest virus (RPVL), measles virus (MV), and canine distemper virus (CDV).
      The gene has an open reading frame of 1575 nucleotides and encodes a protein of
      525 amino acids with a molecular weight of 59 kDa. The nucleotide sequence of the
      coding region of the N gene of RPVK is 88.6, 68.9, and 63.2% homologous with N
      genes of RPVL, MV, and CDV, respectively. We have developed a recombinant
      baculovirus that expresses the N protein (rRVN) of RPVK in insect cells (Sf9) and
      larvae (Spodoptera frugiperda). rRVN was used as a coating antigen in an ELISA to
      distinguish vaccinated animals from those infected with RPV and was also used
      successfully in the diagnosis of two other morbilliviruses, MV and peste des
      petits ruminants (PPRV). Crude lysate of a single infected larva (0.2-0.3 g) was
      sufficient to coat 150 ELISA plates for serological diagnosis of 7200 serum
      samples in duplicate.

PMID- 8259650
TI  - Identification of viral membrane proteins required for cell fusion and viral
      dissemination that are modified during vaccinia virus persistence.
AB  - Wild-type vaccinia virus WR strain forms non-fusogenic (F-) large plaques and is
      hemagglutinin positive (HA+) under normal conditions of virus infection. We have
      analyzed a collection of spontaneous, highly attenuated mutants of vaccinia virus
      isolated from persistently infected Friend erythroleukemia cells (E. Paez, S.
      Dallo, and M. Esteban, J. Virol. 61, 2642-2647, 1987) for the ability to express
      HA during virus infection. After 14 cell passages, all the mutants isolated were
      hemadsorption negative (HAD-) and did not synthesize a HA that could be
      recognized by anti-HA monoclonal antibodies. All these HA- mutants induced
      extensive cell-cell fusion (F+), with the exception of two mutants (65-16 and 101
      14) isolated from late cell passages. Nucleotide sequence analysis of the HA gene
      in these two mutants confirmed the HA- phenotype. A frameshift mutation very
      close to the initiation codon resulted in premature translational termination.
      The truncated gene now only encodes the first 25 amino acids. Analysis of progeny
      from "wild-type," like early serial passage virus (5-3) X mutant back crosses,
      shows that for one late passage non-fusogenic small-plaque mutant (101-14) among
      large plaque progeny there is good correspondence between the ability to fuse and
      the absence of a viral HA and that each large plaque mutant contains a normal 14
      kDa membrane protein. However, with a second serial passage mutant 65-16, which,
      like 101-14, is a nonfusogenic small-plaque variant, there is again an excellent
      correlation between the inability to synthesize HA and the ability to fuse, but
      there is no correlation of plaque size with a normal 14 kDa viral membrane
      protein, as most large plaque mutants encode a larger, i.e., 17 kDa protein.
      Rescue experiments of 65-16 with bona fide cloned 14 kDa protein gene confirm
      that the ability to regulate plaque size and cell fusion in this mutant is due to
      a protein other than the 14 kDa protein. Marker rescue experiments indicated that
      the map position of the additional mutation coincided with a small deletion
      occurring in the HindIII F fragment. This deletion affected the 5'-end and
      promoter sequences of the 37 kDa envelope protein gene and produced a lack of
      expression of this protein, shown by others to be involved in the formation of
      extracellular enveloped virus in infected cells. These results shown that viruses
      with mutations of viral membrane proteins required for cell fusion and viral
      dissemination are selected during vaccinia virus persistence in cell culture.

PMID- 8259651
TI  - Elevated wild-type p53 protein levels in human epithelial cell lines immortalized
      by the human papillomavirus type 16 E7 gene.
AB  - The role tumor suppressors p53 and retinoblastoma (RB) play in the transformation
      process has become central to understanding the pathogenesis of DNA tumor
      viruses. The two oncoproteins of human papillomavirus (HPV)-16, E6 and E7, bind
      to p53 and RB, respectively, thus inactivating the function of these tumor
      suppressor genes. Immortalization of primary human foreskin epithelial cells by
      HPV requires expression of the E7 protein, and the E6 protein greatly enhances
      the immortalization frequency. Two of three cell lines immortalized by the HPV-16
      E7 oncoprotein expressed wild-type p53 and only one of the three cell lines had
      acquired a p53 mutation and loss of heterozygosity at 17p during the
      immortalization process. All three E7-immortalized lines contained higher steady
      state levels of p53 protein. Mutation of the p53 gene is not required for
      immortalization in the absence of the HPV-16 E6 inactivation of the p53 protein,
      and 16E7 expression leads to the stabilization of wild-type p53.

PMID- 8259652
TI  - The major capsid protein of the lipid-containing bacteriophage PR4 is the
      precursor of two other capsid proteins.
AB  - We report that capsid proteins P16 and P18 of bacteriophage PR4 are synthesized
      by post-translational processing of a portion of the major capsid protein, P2. A
      polyclonal antibody raised against purified P2 reacted with P16 and P18 as well
      as with P2. A monoclonal antibody reacted with both P2 and P18. The amino acid
      sequences of the N-termini of P2 and P18 exactly matched, indicating that P18 is
      derived from the N-terminal segment of P2. These data were confirmed by the
      analysis of the proteins encoded by various nonsense and missense P2 mutants. The
      3129-bp MnlI-C fragment of the PR4 genome was shown to encode P2. The nucleotide
      sequence of this fragment was obtained and a single continuous ORF was found to
      encode P2, thus excluding introns and transcript processing in the production of
      P16 and P18. The DNA segment contained eight ORFs sized > 200 bp and the genes
      encoding proteins P6 and P6A as well as P2 were mapped by marker rescue analysis.
      We also report the isolation and characterization of a new class of P2 missense
      mutants.

PMID- 8259653
TI  - Two dominant neutralizing antigenic determinants of canine parvovirus are found
      on the threefold spike of the virus capsid.
AB  - The 25-nm diameter parvovirus capsid is assembled from 60 copies of a sequence
      common to the overlapping VP1 and VP2 proteins. Here we examine the epitope
      specificity's of 28 monoclonal antibodies (MAb) prepared against canine
      parvovirus (CPV), feline panleukopenia virus (FPV), and raccoon-dog parvovirus or
      blue (Arctic) fox parvovirus. Comparing the reactivity of those MAb with various
      MAb-selected escape mutants, or with natural variants of CPV or mink enteritis
      virus (MEV) which differ at known sequences, showed that the binding of 20 of
      those MAb was strongly affected by variations of two regions on the threefold
      spike of the CPV capsid. One region was adjacent to the tip of the threefold
      spike, and the second was around VP2 residue 300, on the shoulder of that
      structure. MAb recognizing both antigenic sites efficiently neutralized the virus
      infectivity and inhibited hemagglutination. Mutations leading to natural
      antigenic variation have also been observed in both those sites in naturally
      variant strains of CPV or MEV, suggesting that they are important antigenic
      structures on these parvoviruses. The bindings of several MAb were not affected
      by the mutations at those antigenic sites, indicating that they recognized other,
      and perhaps conserved, structures.

PMID- 8259654
TI  - Pathogenicity of a subgroup C feline leukemia virus (FeLV) is augmented when
      administered in association with certain FeLV recombinants.
AB  - There is evidence to suggest that infectious feline leukemia viruses (FeLVs) may
      be altered biologically because of homologous recombination with non-infectious
      endogenous FeLV (enFeLV) sequences in the infected cells. To evaluate the role of
      such recombination events in FeLV pathogenesis, a molecular clone of subgroup C
      FeLV, Sarma strain (FSC), was tested for induction of aplastic anemia in the
      absence or presence of mixtures of recombinants between FSC and an enFeLV
      element. In the recombinants, FSC sequences in the viral surface glycoprotein
      (SU) protein were variably replaced by the corresponding sequences of the enFeLV.
      The results showed that the virus mixtures varied in their infectivity to
      neonatal specific pathogen-free cats. One group of mixtures, although exhibiting
      relatively reduced infectivity, represented the most acute disease-inducing
      agents. The presence of recombinants in this mixture significantly accelerated
      the development of erythrocyte aplasia compared to cats infected with FSC alone.
      In addition, infected cells appeared to be distributed differently in various
      hematopoietic organs with respect to infection with FSC versus viral mixture.
      Viral recombinants which were present in this inoculum mixture, however, could
      not be detected in the plasma or infected tissues of the cats at the end stage of
      the disease, although their presence in the plasma at the early stages could be
      detected. Clearly, parental FSC outgrew the recombinants in the infected animals,
      since its detection was prominent at all stages of the progression of the
      disease. Therefore, we hypothesize that recombinants initially present in the
      infected animals, while only poorly replicated compared to FSC in the host, might
      have had the opportunity to infect certain target cells (potentially erythroid
      progenitor cells) and then disappeared with the associated cytopathic effect.

PMID- 8259655
TI  - Serological relationships among viruses in the Hantavirus genus, family
      Bunyaviridae.
AB  - We examined the serological relationships among 32 hantavirus isolates collected
      from numerous geographic regions and hosts. We prepared rat immune sera to each
      virus and used these sera in hemagglutination inhibition (HAI) tests, enzyme
      linked immunosorbent assays (ELISA), and plaque-reduction neutralization tests to
      establish the antigenic relationships among the isolates. Our studies included
      viruses that had been partially characterized previously, as well as isolates for
      which little or no serological data were available. Our results indicate that, in
      addition to the four established serological groups of hantaviruses, represented
      by Hantaan, Seoul, Puumala, and Prospect Hill viruses, there exist at least two
      other distinct groups of hantaviruses. These groups are represented by Thailand
      749 virus, an isolate from Bandicota in Thailand, and by Thottapalayam virus, an
      isolate from Suncus in India. To compare more closely the antigenic relationships
      of the isolates to prototype Hantaan virus, we examined the reactivities of
      Hantaan G1- or G2-specific monoclonal antibodies with the envelope proteins of a
      number of the isolates. We found that several epitopes defined by monoclonal
      antibodies to the G2 protein were highly conserved as detected by HAI tests and
      ELISA. Almost all of the isolates could be neutralized by at least one G2
      specific monoclonal antibody. In contrast, epitopes defined by G1 monoclonal
      antibodies were conserved only among Hantaan-like viruses.

PMID- 8259656
TI  - Phylogenetic analyses of virus isolates in the genus Hantavirus, family
      Bunyaviridae.
AB  - We constructed a phylogenic tree by pairwise comparison of the deduced amino acid
      sequences encoded in the medium (M) genome segments of 13 hantaviruses. Five
      distinct branches were identified, four of which are represented by Hantaan,
      Seoul, Puumala, and Prospect Hill viruses. These groups corresponded to those
      previously established by serological and genetic means. In addition, we present
      sequence information for the M segment of Thailand virus and demonstrate that it
      represents a unique, fifth branch on the dendrogram. We show that a tree nearly
      identical to that constructed from the deduced amino acids encoded in the M
      segments of these viruses can be constructed by comparing nucleotide sequences of
      a 333-bp region of the M segments of the same hantaviruses. This region can be
      amplified, for most hantaviruses, by reverse transcriptase-polymerase chain
      reaction (RT-PCR) techniques, using a single primer pair. By using this method,
      we constructed a consensus tree for 30 hantaviruses, including 15 isolates for
      which we PCR-amplified and sequenced the 333-bp region. In addition to the five
      branches described above, we identified a sixth unique hantavirus group
      represented by Dobrava virus, an Apodemus isolate from Slovenia. Although we were
      unable to PCR-amplify the M segment of Thottapalayam virus, a distantly related
      hantavirus isolated from a shrew captured in India, we were able to amplify,
      clone, and sequence a portion of the small (S) segment of that virus. When we
      compared our Thottapalayam sequence to corresponding S segment sequences of other
      hantaviruses, the results indicated that this virus may represent a seventh,
      distinct group of hantaviruses.

PMID- 8259657
TI  - Multiple genetic determinants of barley stripe mosaic virus influence lesion
      phenotype on Chenopodium amaranticolor.
AB  - The ND18 and Type strains of barley stripe mosaic hordeivirus (BSMV) differ in
      the local lesion phenotypes they elicit on Chenopodium amaranticolor. The ND18
      strain produces large necrotic lesions on this host by 3 to 4 days
      postinoculation, whereas the Type strain is less virulent and elicits chlorotic
      local lesions which appear about 2 weeks after inoculation. We have used
      infectious in vitro transcripts derived from full-length cDNA clones of these two
      BSMV strains to investigate the genetic basis for their differential virulence on
      C. amaranticolor. Pseudorecombination of the wild-type alpha, beta, and gamma
      genomic RNAs of each strain revealed that the lesion forming phenotype segregated
      with RNA gamma. Fine mapping of the phenotypic determinants on RNA gamma was
      carried out by constructing deletion mutants, chimeric recombinants, and point
      mutants. These experiments showed that three different genetic elements in the
      Type strain RNA gamma contribute significantly to its attenuated virulence on C.
      amaranticolor. In addition, pseudorecombination experiments using mutant Type
      strain gamma RNAs that were more virulent than native Type RNA gamma indicated
      that the clean segregation of the lesion forming phenotype observed with wild
      type RNA gamma is fortuitous. This lesion phenotype is dependent on both the
      multiple attenuating determinants in the wild-type Type strain RNA gamma and the
      source of genomic RNAs alpha and beta in the inoculum. The complexity of these
      virulence determinants clearly illustrates the limitations of classical
      pseudorecombination as a tool for the genetic analysis of plant viruses.

PMID- 8259658
TI  - Influenza A virus late mRNAs are specifically retained in the nucleus in the
      presence of a methyltransferase or a protein kinase inhibitor.
AB  - The synthesis of influenza A virus RNA and proteins represents a highly regulated
      process whereby variable amounts of early and late viral RNAs and proteins may be
      produced. This regulation is upset by the presence of the methyltransferase
      inhibitor 3-deazaadenosine (3DA-Ado) or the protein kinase inhibitor H7,
      resulting in complete or partial inhibition of synthesis of late proteins but
      normal production of early proteins. Although the total yield of viral mRNAs is
      somewhat reduced by treatment with 3DA-Ado, the mRNAs that are produced can still
      be translated in vitro. Both 3DA-Ado and H7 interfere specifically with the
      transport of the late viral mRNAs from the nucleus to the cytoplasm, but do not
      affect transport of early mRNA. From these results we conclude that during
      influenza virus replication, posttranscriptional regulation takes place on the
      level of mRNA transport. Since hemagglutinin mRNA migrates to the cytoplasm in
      the presence of 3DA-Ado plus cycloheximide, we assume that a viral protein is
      involved in the regulation mechanism.

PMID- 8259659
TI  - HIV-1 induces down-regulation of bcl-2 expression and death by apoptosis of EBV
      immortalized B cells: a model for a persistent "self-limiting" HIV-1 infection.
AB  - Interactions between HIV-1 and EBV were studied in HIV-1-infected EBV-positive
      lymphoblastoid B cells. Following in vitro exposure of B cells to HIV-1, the
      number of infected cells reached a plateau (25-35%) in approximately 20 days and
      remained fairly stable thereafter, despite the presence of infectious virus in
      culture supernatants. HIV-1-positive (gp120+) were separated from HIV-1-negative
      (gp120-) cells, and the two fractions were further characterized for EBV
      antigens, bcl-2 expression, and growth capacity in vitro. Compared to gp120-
      cells, EBNA 1, EBNA 2, and LMP 1 were down-regulated, and the episomal form of
      EBV-DNA was dramatically decreased in the gp120+ cells. When plated in culture
      gp120+, but not gp120-, cells died; BZLF1 antigen was not expressed, thus ruling
      out a reactivation of the EBV lytic cycle. Cytofluorometric, morphological, and
      molecular analyses disclosed that gp120+ cell death was due instead to apoptosis;
      evidence of bcl-2 down-regulation in these cells was consistent with this
      finding. gp120+ cell apoptosis contributed to keeping the level of HIV-1-infected
      cells at a steady state in the unfractionated culture, where persistent infection
      was maintained by HIV-1 transmission to B cells newly arising from the
      proliferation of HIV-1-uninfected cells.

PMID- 8259660
TI  - Lipid selection in the assembly of the phospholipid bilayer membrane of the lipid
      containing bacteriophage PR4.
AB  - Phage PR4 contains a lipid bilayer within the phage protein capsid. The
      phospholipids of the bilayer are derived from those of the host. We report that
      phage morphogenesis selects against the unusually bulky phospholipids synthesized
      by Escherichia coli grown in the presence of various sugar alcohols. These data
      indicate that assembly of the PR4 lipid bilayer is a selective process rather
      than the bulk appropriation of host membrane lipids. We also demonstrates that
      phage PR4 morphogenesis is compatible with the incorporation of several abnormal
      lipids, monoacylglycerol, diacylglycerol, and phosphatidylinositol into the phage
      particle.

PMID- 8259661
TI  - Antibody response in cats to the envelope proteins of feline immunodeficiency
      virus: identification of an immunodominant neutralization domain.
AB  - Overlapping fragments of the envelope protein of feline immunodeficiency virus
      (FIV) have been expressed in Escherichia coli. Screening of cat sera for
      antibodies to these fragments revealed that the immunodominant domain of the FIV
      envelope is localized within the transmembrane protein (amino acids 687-741) and
      that both the variable region 3 (SU3, aa 385-417) and the COOH-terminus (aa 599
      611) of the surface protein (SU) are highly immunogenic. Of all rabbit sera
      raised to the envelope protein fragments only the serum directed to SU3 was
      neutralizing. Both FIV-infected and SU3-immunized cats elicited neutralizing
      antibodies to SU3. Neutralizing antibodies in sera of infected cats could be
      absorbed by SU3, showing that SU3 is a major neutralization domain of FIV.

PMID- 8259662
TI  - Moesin: a cell membrane protein linked with susceptibility to measles virus
      infection.
AB  - Measles virus is a highly contagious virus causing acute and persistent diseases
      in man, the receptor of which is still not well characterized. We have isolated a
      monoclonal antibody (mAb), designated mAb 119, which specifically inhibits
      measles virus infection of susceptible cell lines in a dose-dependent manner.
      This antibody precipitates a protein with an apparent molecular mass of 75 kDa
      from 125I surface-labeled cells and its epitope is present on human peripheral
      blood mononuclear cells, human cell lines, and the African green monkey cell line
      Vero. Affinity chromatography of detergent-solubilized cell membrane proteins
      over a Sepharose column with covalently bound mAb 119 led to the partial
      purification of the 75-kDa protein. Preincubation of measles virus with this
      affinity-purified protein inhibited measles virus infection dose dependently.
      Amino acid microsequencing of this protein revealed its identity with the human
      membrane-organizing extension spike protein moesin, a protein intra- and
      extracellularly associated with the plasma membrane of cells. Subsequently, an
      antibody raised against purified moesin (mAb 38/87) was also found to
      specifically inhibit measles virus infection of susceptible cells and confirmed
      our data obtained with mAb 119. Our data suggest that moesin is acting as a
      receptor for measles virus.

PMID- 8259663
TI  - Proteinase 3C of hepatitis A virus (HAV) cleaves the HAV polyprotein P2-P3 at all
      sites including VP1/2A and 2A/2B.
AB  - Thus far, the only virus-encoded proteinase of hepatitis A virus (HAV) detected
      is 3C, which was shown to catalyze proteolysis of most of the suggested cleavage
      sites within the HAV precursor polyprotein. To elucidate whether or not HAV
      proteinase 3C and its precursors are involved in processing of the yet
      unidentified sites in the polyprotein P2-P3, the genomic region of 3C including
      flanking sequences were expressed in a bacterial system and by cell-free
      translation. In both systems 2A-reactive proteins of 10 (2A) and 16 kDa (delta
      VP1-2A) were processing products of a polyprotein representing delta VP1-P2-P3*
      (delta and * denote N- or C-terminally truncated proteins, respectively), thus
      providing evidence for cleavage at sites VP1/2A and 2A/2B by proteinase 3C. In
      the cell-free expression system, processing at the P2/P3 junction was rapid and
      complete, whereas sites 3A/3B, 3B/3C, and 3C/3D were inefficiently cleaved, as
      evidenced by the accumulation of the stable precursor polypeptides P3* and 3ABC.
      In contrast to the eukaryotic system, mature 3C was produced in Escherichia coli.
      Intermolecular cleavage by recombinant 3C occurred at all putative sites within
      the proteolytically inactive polyprotein P2-P3* mu. The results of this study
      indicate that proteinase 3C mediates the primary as well as the secondary
      cleavages of the HAV polyprotein and thus shows an activity profile broader than
      that of 3C proteinases of other picornaviruses.

PMID- 8259664
TI  - Fullerene-like organization of HIV gag-protein shell in virus-like particles
      produced by recombinant baculovirus.
AB  - Virus-like particles produced by a recombinant baculovirus containing the HIV gag
      gene were examined by negative staining after delipidization. This technique
      demonstrated that the gag-protein shell consisted of radially arranged short rods
      which formed a network of ring-like structures. Similar structures were observed
      at the plasma membrane of infected cells which had been opened by wet-cleaving.
      Occasionally five or six subunits were observed forming a ring. These findings
      suggest that the gag-encoded precursor (pr55) is a rod-like molecule about 34 A
      in diameter and 85 A in length. A protein cylinder of such dimensions would have
      a molecular weight of 56K. The center-to-center distance of two neighboring rings
      formed by the rods was 66 +/- 8 A (N = 200) by direct measurements and 65 A as
      obtained from averaged images. This morphology and these dimensions indicate that
      the virus-like particles contain the gag precursor in the form of a near
      spherical "fullerene-like" icosahedral shell. Our data indicate that the
      triangulation number of the rings equals 63. However, since one rod of pr55 is
      shared by two rings, the number of copies of the precursor will be 1890 as
      opposed to 2522 if the molecules were closely packed. The particle diameter of
      102 nm deduced from the proposed model was close to the diameter obtained from
      thin sections of low-temperature-embedded specimens (103-108 nm).

PMID- 8259665
TI  - Seroepidemiologic, molecular, and phylogenetic analyses of simian T-cell leukemia
      viruses (STLV-I) from various naturally infected monkey species from central and
      western Africa.
AB  - A study of simian T-cell lymphoma/leukemia virus infection, conducted on 747
      nonhuman primates belonging to 14 different species in Central and Western
      Africa, indicated that 4 species (Cercopithecus aethiops, Erythrocebus patas,
      Papio doguera, and Cercopithecus mona pogonias) had a high prevalence of
      seropositivity to simian T-cell lymphoma/leukemia virus type I (STLV-I). The
      other nonhuman primate species, however, had negative or low levels of anti-HTLV
      I antibodies. STLV-I pol and env DNA was detected in 12 of 12 different animals
      among the seropositive species. However, STLV-I pX DNA could be detected in only
      10 of 12 animals. Comparative phylogenetic analyses based on 140 bp sequence of
      the pol gene indicate that these STLV-I isolates were 0-9% divergent from each
      other and were 3.5-7% divergent from the prototype related human retrovirus HTLV
      I (ATK). The West African STLV-I isolates formed a unique phylogenetic cluster as
      did most of the Central African STLV-I isolates, save for STLV-I (Tan 90). The
      phylogenetic data indicate that cross species transmission of HTLV-I and STLV-I
      continued to occur long after their ancestral strain separated from the
      progenitor to HTLV-II. Comparative amino acid analyses indicated that there was
      marked conservation of the TAX protein regardless of host species, while the pol
      and REX proteins exhibited increasing levels of diversity.

PMID- 8259666
TI  - Beet yellows closterovirus: complete genome structure and identification of a
      leader papain-like thiol protease.
AB  - The sequence of 8734 nucleotides (nt) from the 5'-end of the beet yellows
      closterovirus (BYV) RNA was determined to complete the 15,480-nt sequence of the
      virus genome. The 5'-terminal two-thirds of the sequence are occupied by two
      overlapping open reading frames (ORFs) 1a and 1b, encoding products with
      calculated M(r) of 295K and 48K, respectively. The RNA sequence surrounding the
      stop codon in ORF 1a shows structural elements typical of ribosomal frameshifting
      signals in a number of animal and plant viruses. It is predicted that the ORF 1b
      product is expressed via a +1 ribosomal frameshifting as the 348K ORF 1a/1b
      fusion protein. This putative protein contains the array of methyltransferase,
      RNA helicase, and RNA-dependent RNA polymerase domains that is conserved in the
      Sindbis-like supergroup of positive-strand RNA viruses. The 348K protein of BYV
      is longer than the putative replicases of the most closely related viruses (tobra
      and tobamoviruses) by about 1300 amino acids distributed between two unique
      regions, one at the N-terminus, and the other in the central portion. The N
      terminal domain showed sequence similarity to the helper component papain-like
      protease of potyviruses. By using in vitro translation of the T7 transcripts
      encoding the N-terminal 92K peptide of the BYV ORF 1a product, we found that the
      N-terminal fragment of 588 amino acids is released from the translation product
      by cleavage at the Gly-Gly dipeptide. Site-directed mutagenesis of either of the
      predicted catalytic residues Cys-509 and His-569 or of the Gly-588 at the
      cleavage site completely abolished the cleavage. The central unique region of the
      348K protein contains a domain distantly resembling the aspartic protease of HIV
      and other lentiviruses. As shown previously, the 3'-terminal portion of the BYV
      genome encompasses seven more ORFs, one of which codes for a protein related to
      the HSP70 cell heat shock proteins, whereas two others encode the capsid protein
      and its diverged copy. Thus, despite the apparent evolutionary relationship with
      Sindbis-like viruses, BYV comprises a collection of genomic modules absorbed from
      different sources and has a unique expression strategy.

PMID- 8259667
TI  - Differences in plaque size and VP4 sequence found in SA11 virus clones having
      simian authentic VP4.
AB  - We isolated five stable SA11 clones (TN-S1, TN-S2, TN-L1, TN-L2, and BN-S4) with
      different plaque sizes from two SA11 stocks. In polyacrylamide gel
      electrophoresis, the mobilities of the fourth, fifth, and seventh RNA segments of
      SA11 clones with large plaque size (TN-L1 and TN-L2) were faster than those of
      clones with small plaque size (TN-S1, TN-S2, and BN-S4). Nucleotide sequence
      determination of the fourth RNA segment identified a five-amino-acid difference
      in VP4s between the clones with large and small plaque sizes. The VP4 sequences
      of two clones with small plaque size (TN-S1 and BN-S4) were the same as the
      sequence of SA11-SEM reported by K. Nishikawa et al. (1988, J. Virol. 62, 4022
      4026), while the VP4 sequences of the clones with large plaque size (TN-L1 and TN
      L2) were similar, but not identical, to that reported by D. B. Mitchell and G. W.
      Both (1989, Nucleic Acids Res., 17, 2122). A single-gene reassortant, K8-L2.4, in
      which RNA segment 4 was derived from clone TN-L2 of SA11 virus and the other RNA
      segments were from strain K8, produced large plaques like TN-L2, suggesting that
      the five-amino-acid difference in VP4 between the clones with large and small
      plaque sizes might be associated with the difference in plaque size.

PMID- 8259668
TI  - A short sequence upstream of the 5' major splice site is important for
      encapsidation of HIV-1 genomic RNA.
AB  - A series of linker scanning and deletion mutations has been constructed in the 5'
      leader sequence of HIV-1. One virus with a 13-base-linker substitution upstream
      of the 5' major splice site was as impaired in its ability to replicate as a
      virus with a large deletion, which included these 13 bases, and was less
      efficient in packaging its genomic RNA than viruses carrying mutations between
      the 5' major splice site and the gag translation initiation site. These
      observations have led to the identification of a conserved pattern of repeated
      sequence elements associated with sequences experimentally defined as necessary
      for encapsidation of Moloney murine leukemia virus, spleen necrosis virus, avian
      leukosis-sarcoma viruses, and human immunodeficiency virus type 1.

PMID- 8259669
TI  - Alteration in the JC polyomavirus genome is enhanced in immunosuppressed renal
      transplant patients.
AB  - JC polyomavirus (JCV) DNAs derived from urine generally contain an archetypal
      regulatory sequence, whereas regulatory regions of JCVs in the brain with
      progressive multifocal leukoencephalopathy (PML) have specifically altered
      regulatory regions. However, JCV DNAs with regulatory regions that deviate from
      the archetype sometimes occur in the urine of non-PML patients. In this study, we
      compared the incidence of these rearranged regulatory regions between
      immunosuppressed (renal transplant recipients) and nonimmunosuppressed patients.
      We found that the incidence of rearranged JCV regulatory regions was
      significantly higher in renal transplant patients than that in
      nonimmunosuppressed patients. This finding suggests that immunosuppression would
      permit accumulation of JCV with rearranged regulatory regions. On the other hand,
      from the following observations, we conclude that rearranged regulatory regions
      unique to PML-type JCVs rarely occur even in renal transplant patients: (1)
      rearrangements in JCVs from these patients were almost exclusively simple, that
      is deletions or duplications; (2) duplication of domain A or deletion of domain
      B, each being a feature common to most PML-type regulatory regions, was rarely
      detected in JCVs from the patients. The data are consistent with the fact that
      PML is a rare disease in patients with decreased immune competence and support
      the hypothesis that changes in the JCV regulatory region may be involved with the
      etiology of PML.

PMID- 8259670
TI  - Passively transferred African swine fever virus antibodies protect swine against
      lethal infection.
AB  - The role of anti-viral antibodies in homologous protective immunity to a virulent
      African swine fever virus (ASFV) strain E75 was examined by passive transfer
      experiments in swine. Eighty-five percent of animals (n = 14) that received anti
      ASFV immunoglobulin (Ig) survived challenge infection, while 100% mortality was
      observed in control group animals (n = 28) that received anti-pseudorabies virus
      Ig, normal swine Ig, or phosphate-buffered saline. With the exception of a
      significantly delayed and transient fever response, anti-ASFV Ig group animals
      remained clinically normal following challenge, whereas control group animals
      presented with clinical ASF on Day 4 postchallenge. Additionally a significant 3
      day delay in onset of viremia and a 10,000-fold reduction in both mean and
      maximum virus titers were observed for animals given anti-ASFV Ig. These results
      indicate that anti-ASFV Ig alone will protect swine from lethal infection with
      virulent ASFV. Further, they support the view that the antibody-mediated
      protective effect is an early event that effectively delays disease onset.

PMID- 8259671
TI  - A murine coronavirus MHV-S isolate from persistently infected cells has a leader
      and two consensus sequences between the M and N genes.
AB  - A plaque-cloned mouse hepatitis virus mutant, MHV-S No. 8, was isolated from Ki
      BALB cells persistently infected with MHV-S. The mRNAs 1 to 6 were larger in the
      mutant, whereas there was no difference between the two viruses in the size of
      the smallest mRNA, mRNA 7. Sequence analyses of the genomic RNA, mRNA 6, and mRNA
      7 of the two viruses revealed that an additional 111 nt were inserted just
      upstream of the intergenic consensus sequence preceding the N gene in MHV-S No.
      8. The inserted region consisted of two different parts; the 3'-most 30 nt
      corresponded to nucleotides 28 to 57 of the leader sequence and the 5'-most 81 nt
      corresponded to nucleotides 58 to 138 of mRNA 7. This structure of No. 8 was most
      likely generated by RNA-RNA recombination between genomic RNA and subgenomic RNA
      species. The nucleotide insertion in the intergenic sequence between genes M and
      N resulted in two consensus sequences separated by 111 nt. Primer extension
      analysis revealed that the amount of a slightly larger, subgenomic mRNA resulting
      from initiation of synthesis at the upstream consensus sequence was only 5% of
      the usual sized mRNA 7 initiated from the downstream consensus sequence.

PMID- 8259672
TI  - A unique VP4 gene allele carried by an unusual bovine rotavirus strain, 993/83.
AB  - The VP4 protein of an unusual group A calf rotavirus strain, 993/83 (serotype G7
      and subgroup non-I and non-II), was determined to contain 770 amino acids,
      shorter than any other VP4 proteins sequenced to date. The 993/83 VP4 exhibited
      only 55-62% amino acid identity to the VP4s of the representatives of 12 distinct
      P serotypes, suggesting that 993/83 VP4 represents a new P serotype.

PMID- 8259673
TI  - Analysis of interstrain variation in a putative immediate-early region of human
      herpesvirus 6 DNA and definition of variant-specific sequences.
AB  - Sequences of a 2.6- to 2.9-kb open reading frame in a putative immediate-early
      region of the human herpesvirus 6 (HHV6) genome were determined and compared in
      three reference and six local isolates of HHV6. The sequences segregated into two
      variant groups (A and B) having only 75% nucleotide homology and 62% peptide
      homology, in part because of deletions in the variant A strains. Among the
      variant B isolates, further sequence grouping was evident; two clinical isolates
      segregated with reference strain Z29 into a cluster that had 96.6% nucleotide
      homology and 92.6% peptide homology when compared to a second variant B cluster
      of four isolates. Within each cluster of variant B isolates, nucleotide homology
      was 99.4% or more. Two pairs of isolates had identical sequences. The marked
      divergence of variants A and B permitted the design of variant-specific
      oligonucleotide primers that could detect in a single polymerase chain reaction
      the presence of either or both variant A and B HHV6 DNA. Variation in this gene
      region of HHV6 is more extensive than in the envelope glycoprotein (gB and gH)
      coding regions and could be related to known biological differences between
      variant groups.

PMID- 8259674
TI  - De novo generation and accumulation of tomato bushy stunt virus defective
      interfering RNAs without serial host passage.
AB  - Studies were initiated to monitor generation and accumulation of defective
      interfering (DI) RNAs associated with tomato bushy stunt virus (TBSV) in the
      absence of serial, high multiplicity of infection passage. Infections were
      initiated in Nicotiana clevelandii host plants and protoplast cell suspensions by
      inoculation with in vitro-synthesized infectious TBSV RNA transcripts containing
      a genomic marker. The infections were then assayed for DI-size RNAs by both
      Northern blot analysis and reverse transcription coupled with PCR amplification.
      DI-size RNAs could not be detected by Northern blot analysis in either plants or
      protoplasts after an evident viral infection. However, RT-PCR amplification
      permitted the isolation of DI-size cDNAs (600-700 nt) from plant, but not
      protoplast, infections as early as 8 days postinoculation. Sequence analysis of
      these DI-size cDNA clones revealed that they contained the four conserved regions
      found in all previously identified competent DI RNAs. Several DI RNA clones
      contained the genomic marker which confirmed their de novo generation from the
      input transcript inoculum. A comparison of the nucleotide sequence of these
      clones to previously sequenced DI RNAs, isolated from plants after multiple
      passages, showed that differences existed at the junctions between regions. These
      results demonstrate that a heterogeneous population of DI RNAs accumulated in
      plants in the absence of serial host passage. In addition, the similarity of
      these DI RNAs to previously characterized DI RNAs that accumulate upon passage
      indicates that evolution can occur very rapidly within the initially inoculated
      plant.

PMID- 8259675
TI  - A cell line that expresses a reporter gene in response to infection by Sindbis
      virus: a prototype for detection of positive strand RNA viruses.
AB  - We describe a stably transformed cell line (BHKSINLuc2) that contains a defective
      Sindbis virus genome under the control of a Rous sarcoma virus promoter and the
      luciferase gene downstream of the viral subgenomic RNA promoter. This cell line
      expresses high levels of luciferase activity following infection with Sindbis
      virus and provides a sensitive assay for titering variants of Sindbis virus that
      lack the structural protein genes, in particular, Sindbis virus replicons that
      express heterologous proteins. Cell lines such as this may be of value for
      detection of positive-strand RNA viruses.

PMID- 8259676
TI  - Equid herpesviruses 1 and 4 encode functional homologs of the herpes simplex
      virus type 1 virion transactivator protein, VP16.
AB  - The herpes simplex virus type 1 (HSV-1) tegument protein VP16 is a potent
      transcriptional inducer of immediate-early gene expression, comprising an N
      terminal domain involved in binding DNA linked to an acidic transactivating C
      terminal domain. The gene encoding the counterpart of this protein in equid
      herpesvirus 4 (EHV-4) was sequenced. Comparisons with VP16 and the homologous
      proteins of equine herpesvirus 1 (EHV-1) and varicella-zoster virus (VZV) showed
      that a region in the N-terminal domain involved in formation of a complex with
      cellular proteins is partially conserved in all four proteins. In contrast, the C
      terminal regions of the EHV proteins, like that of VZV, are not particularly
      acidic and are not significantly conserved with respect to the C-terminal region
      of VP16. Nevertheless, transient expression experiments indicated that the EHV-1
      and EHV-4 proteins are able to transactivate HSV-1 and EHV-1 immediate-early
      promoters in a dose-dependent manner, which suggests that this activity is not
      dependent on an acidic C-terminal domain.

PMID- 8259677
TI  - Analysis of figwort mosaic virus (plant pararetrovirus) polyadenylation signal.
AB  - Analysis of the cauliflower mosaic virus (CaMV) polyadenylation (poly(A)) signal
      has revealed several striking differences to poly(A) signals from animal genes
      such as the absence of activating sequences downstream from the cleavage site.
      Instead, upstream sequences were shown to induce recognition of an AAUAAA
      sequence. To test whether these features are representative of other plant
      pararetrovirus poly(A) signals, a characterization of the figwort mosaic virus
      (FMV) poly(A) signal is presented here. The FMV RNAs were isolated from infected
      plants and mapped, and the different elements composing the FMV poly(A) signal
      were identified. Multiple upstream sequences were found to be essential for
      efficient processing at the FMV poly(A) site and could be replaced by the CaMV
      upstream elements. The FMV upstream sequences showed homologies to other
      characterized upstream sequences from CaMV, from animal viruses, and from plant
      poly(A) signals. Surprisingly, neither the FMV nor the CaMV upstream elements
      could induce recognition of an AAUAAA sequence present in the FMV poly(A) signal,
      instead a UAUAAA sequence 55 nucleotides further downstream was utilized. It is
      proposed that additional features may be required for appropriate cleavage such
      as the context of the AAUAAA-like sequence or perhaps the cleavage site itself.

PMID- 8259678
TI  - Immunodominant antigenic regions in a structural protein of the hepatitis E
      virus.
AB  - Using a set of 11 synthetic peptides containing regions of the polypeptide
      encoded by open reading frame 2 (ORF2) of the hepatitis E virus (HEV) genomic
      RNA, two immunodominant regions were found. One region is located at position 546
      580 amino acids (aa). Another very strong immunodominant region was identified at
      position 394-470 aa. Five peptides spanning this region were found to have
      antigenic reactivity. One of these 5 peptides demonstrated specific reactivity
      with 81% of sera obtained from HEV-infected patients. To elucidate the antigenic
      structure of this region in fine detail, an additional set of 35 overlapped 20
      mer peptides spanning the region 388-493 aa was synthesized. Two subregions with
      very strong antigenic reactivity, one located around position 420-440 aa and
      another around 450-460 aa, were identified. Thus, in addition to the strong
      epitope(s) in the C-terminal region of the ORF2 protein previously identified, at
      least two immunodominant regions were found at positions 394-470 and 546-580 aa.

PMID- 8259680
TI  - Measles virus V protein binds zinc.
AB  - Measles virus transcription generates multiple P/C gene-specific mRNAs by a
      process which has been termed editing. In one of these mRNAs, the
      cotranscriptional addition of a single nontemplated G residue allows
      translational access to the V protein reading frame. The protein translated from
      this mRNA has been called V and consists of 231 amino-terminal amino acid
      residues identical to those at the amino terminus of the P protein followed by a
      unique carboxy-terminal domain consisting of 68 amino acids from the V reading
      frame. The most striking feature of this unique domain is the presence within it
      of seven cysteine residues whose presence and position are highly conserved among
      different paramyxoviruses. The number and arrangement of these cysteine residues
      is suggestive of a zinc finger protein. We have used a zinc binding protocol to
      determine that V protein does indeed bind zinc, have further demonstrated that
      this metal binding activity is highly specific to zinc, and have shown that it is
      the unique carboxy-terminal domain of the V protein that is responsible for zinc
      binding.

PMID- 8259679
TI  - Studies on the influence of the VP7 gene on rotavirus replication.
AB  - In a previous study using reassortant viruses, bovine rotavirus B223 VP7 protein
      enhanced the neutralization titers of some VP4 specific cross-reactive monoclonal
      antibodies (MAbs) (Xu and Woode, Virology, 1993). In this report, the influence
      of the B223 VP7 gene on the growth of reassortants was studied. The growth curves
      of three B223/69M reassortants with or without the B223 VP7 gene were compared.
      Reassortant M8, which has B223 VP7 on the genetic background of 69M, replicated
      as fast and to a similar titer as B223 and better than 69M. In contrast, the
      growth of reassortants B9, which has 69M VP7 on the B223 background, and of M46,
      which has B223 VP4 and VP6 on the 69M background, were poorer than B223. As B223
      VP7 appeared to provide replication advantages, B223 was cultured as co
      infections with each of the following viruses: Wa, 69M, H-2, SA11-4F, and NCDV
      followed by 20 subpassages. For co-infections with Wa, 69M, H-2, and SA11-4F,
      B223 VP7 gene was selected, in contrast to the B223/NCDV co-infection, when NCDV
      VP7 gene was selected. Other genes were also selected non-randomly, but varied
      among the five co-infection pairs. These data suggest in particular that B223 or
      NCDV VP7 protein can provide replication advantages to reassortant viruses,
      possibly by modifying VP4 to make it adsorb more efficiently to the cell
      receptors.

PMID- 8259681
TI  - Distinct structural elements and internal entry of ribosomes in mRNA3 encoded by
      infectious bronchitis virus.
AB  - Infectious bronchitis virus (IBV) mRNA3 encodes three small proteins, 3a, 3b, and
      3c, at its 5' end. Recently, it was demonstrated that initiation of protein 3c is
      dependent on the upstream sequence. Monte Carlo simulations of RNA folding in
      this tricistronic mRNA3 indicate that a highly significant folding region occurs
      prior to the initiator AUG of 3c. The unusual folding region (UFR) of 265
      nucleotides (nt) contains the coding sequences of proteins 3a and 3b. Details of
      the structural analyses show that five highly significant RNA stem-loops in the
      UFR can be modeled into a compact superstructure by the interaction of two
      predicted pseudoknot structures. The folded superstructure comprising nt 44 to
      330, with additional 22 nt downstream from this UFR, is suggested to serve as a
      ribosome landing pad (or an internal ribosomal entry site) in the cap-independent
      translation of the 3c of IBV. Intriguingly, the proposed structural motif of this
      coronavirus shares structural features similar to those proposed in a number of
      picornavirus mRNAs. Based on the common structural features, a plausible base
      pairing model between mRNA3 and 18 S rRNA is suggested, which is consistent with
      a general mechanism for regulation of internal initiation described in many
      picornaviruses.

PMID- 8259682
TI  - Functional roles of terminal glycomoieties in varicella-zoster virus infection.
AB  - Terminal glycomoieties of varicella-zoster virus glycoproteins were characterized
      by their reactivity with lectins and glycosidases, and the functional roles of
      terminal sugars were analyzed by cell-free virus infectivity. Terminal glycan
      structures of gpl possessed sialic acid linked alpha (2-3) to galactose of O
      linked glycan and galactose-beta (1-4)-N-acetylglucosamine of N-linked glycan.
      Those of the putative gpIV possessed galactose-beta (1-4)-N-acetylglucosamine of
      N-linked glycan. Both glycoproteins had mannose alpha (1-3, 6, or 2) linked to
      mannose in their glycans. Their biological functions on cell-free virus
      infectivity were assessed by using lectins and exoglycosidases. Sialic acid of
      glycans on both the viral envelope and the cell surface had a negative effect on
      infectivity, and the latter had a larger effect on infectivity than the former.
      Maackia amurensis agglutinin, which recognizes sialic acid, enhanced infectivity
      more than expected from the simple neutralization of the negative effects of
      sialic acids between cells and virus. alpha-Mannosidase and alpha-glucosidase
      treatments of virus significantly reduced infectivity but those of cells did not.
      Therefore, alpha-mannose and alpha-glucose residues on the viral envelope had
      functional roles in cell-free virus infection. Inactivation of virus infectivity
      by concanavalin A was mainly due to the blocking of functional roles of terminal
      alpha-mannose and alpha-glucose residues of viral glycoproteins.

PMID- 8259683
TI  - Infection of human polyomaviruses JC and BK in peripheral blood leukocytes from
      immunocompetent individuals.
AB  - Widely disseminated infection with the human polyomaviruses JC and BK is followed
      by lifelong asymptomatic viral persistence that can be reactivated under
      prolonged immunosuppression to fatal CNS and urogenital disease. In an attempt to
      understand the pathogenesis of polyomavirus diseases, we asked whether leukocytes
      are involved in polyomavirus infection in the immunocompetent host. Peripheral
      blood leukocytes from 29 immunocompetent individuals and umbilical cord blood
      from 10 newborn children were analyzed for the presence of polyomavirus DNA.
      Southern blot analysis demonstrated the presence of JCV-specific full-length
      virus genomes and indicated involvement of the second human polyomavirus BK. In
      contrast to specimens from newborn children, PCR amplification of target DNA in
      the adult age group followed by species-specific hybridization provided evidence
      of concomitant JCV and BKV infection in almost all specimens. Nucleotide
      sequencing of virus-specific products representing DNA segments essential for
      virus multiplication confirmed presence of both virus species in leukocytes. The
      detection of a new virus subtype and single base changes or deletions in the
      noncoding DNA region from individual cases suggested widespread heterogeneity in
      the circulating virus population, although the structure of the transcriptional
      control elements in all cases was comparable to highly active elements found in
      lytically infected cells. Those findings and the localization of both virus types
      in the nuclei of blood cells by in situ hybridization demonstrate that JCV and
      BKV frequently infect peripheral leukocytes and give strong evidence that
      leukocytes are common sites of polyomavirus persistence in healthy individuals.

PMID- 8259684
TI  - Analysis of the DNA-binding domain of the HSV-1 origin-binding protein.
AB  - In order to understand DNA-protein interactions at the origin of DNA replication
      in herpes simplex virus type 1 (HSV-1), we have undertaken an analysis of the DNA
      binding domain of the origin-binding protein (OBP) and its mechanism of binding
      to the Oris sequence of HSV-1. Mutant DNA-binding domains were constructed,
      expressed in vitro, and used to test for binding by gel shift analysis. A C
      terminal deletion mutant was functional in binding, thereby redefining the C
      terminal boundary of the DNA-binding domain at amino acid 822. Fifteen insertion
      mutants were also constructed across the DNA-binding domain. Several of these
      mutants were unable to bind DNA. Interestingly, 4 mutants that destroy DNA
      binding fall within a region that has a particularly high degree of sequence
      similarity to the varicella zoster virus gene 51 product. A second objective was
      to define how the DNA-binding domain interacts with the origin. Results of gel
      shift analysis using contranslated proteins of different sizes suggest that the
      DNA-binding domain can interact with a single binding site as a monomer. Binding
      to the wild-type Oris template indicated that the binding domains can interact
      with both binding sites I and II independent of any cooperative effect mediated
      by the amino-termini. This suggests that the basic unit of recognition involved
      in OBP/Oris interactions may contain a single DNA-binding domain of OBP in
      association with a single binding site.

PMID- 8259685
TI  - The cellular U-particle, whose synthesis is induced by mengovirus infection, is
      homologous to apoferritin.
AB  - Mengo virus infection of mouse L-cells results in induction of the synthesis of a
      cellular protein-containing particle, 12 nm in diameter, which was designated U
      (Boege et al. (1987) Virology 159, 358-367). We have purified the U-particle from
      virus-infected cells by a series of chromatographic steps and found it to be
      composed of two polypeptide species (MW 23,000 and 25,000), present in a ratio of
      approximately 7:3. Neither of these polypeptides is measurably glycosylated or
      phosphorylated and the U-particle contains no detectable nucleic acid. Several
      amino acid sequences obtained from CNBr fragments of the U-polypeptides
      identified them as the H- and L-chains of mouse apoferritin. This finding was
      supported by immunoblotting and electron microscopy. In terms of function, the U
      particle/apoferritin effectively inhibits the translation of mRNAs in
      reticulocyte lysates. These experiments indicate that apoferritin may perform
      important functions in eukaryotic cells in addition to iron storage. Finally, we
      propose mechanisms to explain how Mengo virus infection could specifically induce
      the synthesis of apoferritin and how increasing amounts of cytoplasmic
      apoferritin could facilitate virus replication.

PMID- 8259687
TI  - [Immunohistochemical differentiation of granulosa cell tumors and
      undifferentiated ovarian cancers].

PMID- 8259686
TI  - [The CA-125 tumor marker in epithelial ovarian cancers of stage I].
AB  - A precondition for the early diagnosis of ovarian cancer by means of raised
      tumour marker levels is high sensitivity at an early stage of the disease. In
      this study the relationship of the levels of the tumour marker CA-125 to the
      variables age, grading and histological status was examined in 52 patients with
      verified FIGO stage I epithelial ovarian cancer. A liminal value of 35 U/ml was
      accepted and the patients were split into 2 groups according to whether the
      tumour marker exceeded this value or not. The survival probability was calculated
      for each group in order to gauge the prognostic significance of this serum
      marker. Although there was no statistically significant correlation between the
      CA-125 levels established preoperatively and the above-mentioned variables, in
      contrast to other studies we found a higher overall sensitivity of 62%. Of
      particular interest is the considerably higher sensitivity of CA-125 in the
      postmenopausal patients within our collective. The findings of this study suggest
      that marker-positive patients might have a poorer survival prognosis.

PMID- 8259688
TI  - [Papillary microcarcinoma of the thyroid gland].

PMID- 8259689
TI  - Metabolism of piperidine-type phenothiazine antipsychotic agents. IV.
      Thioridazine in dog, man and rat.
AB  - 1. The metabolism of thioridazine was studied in adult male volunteers, female
      rat and female dog after oral administration of 50 mg, 20 mg/kg and 100 mg over
      30 h, respectively. 2. Metabolites in organic extracts of the urine obtained from
      each species were analysed by plasmaspray h.p.l.c.-mass spectrometry. For
      phenolic metabolites the crude extracts from each species were derivatized with a
      silylating reagent (with and without prior enzymic hydrolysis) prior to h.p.l.c.
      mass spectrometric analysis. The structures of metabolites, with the exception of
      phenols, were confirmed by comparison of their chromatographic behaviours and
      mass spectral data with those of authentic standards. 3. The metabolites
      identified in the urine of all three species were mesoridazine, sulforidazine,
      thioridazine ring sulphoxide, mesoridazine ring sulphoxide, sulforidazine ring
      sulphoxide, the lactam of mesoridazine ring sulphoxide and unconjugated phenolic
      derivatives of mesoridazine and sulforidazine. Other compounds observed were:
      unchanged thioridazine (dog, rat), sulforidazine N-oxide (man), N
      desmethylthioridazine ring sulphoxide (dog, rat), N-desmethylmesoridazine ring
      sulphoxide (dog, rat), the lactam of sulforidazine ring sulphoxide (rat, man),
      phenolic derivative of thioridazine in unconjugated form (rat), and conjugated
      form (man), and conjugated phenolic derivative of mesoridazine (man). 4.
      Thioridazine and six of its metabolites present in the urine of man, rat and dog
      were quantified by a h.p.l.c.-UV procedure. The mean total urinary excretion (+/-
      SD) of the measured analytes in man, rat and dog were determined to be 4.3 +/-
      2.9, 4.8 +/- 1.7 and 12.1 +/- 5.4% of the dose, respectively. The mean excretion
      of the lactam of mesoridazine ring sulphoxide was greater in man (1.2 +/- 1.0%)
      and rat (0.2 +/- 0.2%) than dog (< 0.02%). Moreover, the mean excretion of the
      lactam of sulforidazine ring sulphoxide was quantifiable in both man (0.5 +/-
      0.4%) and rat (0.2 +/- 0.2%). 5. Interspecies comparison of the lactam
      metabolites indicated that both qualitatively and quantitatively, man more
      closely resembled rat than dog. Similar observations were previously reported for
      mesoridazine and sulforidazine, therefore rat may be a more suitable animal than
      dog to undertake further study of the importance of C-oxidation of the piperidine
      ring of this class of drug.

PMID- 8259690
TI  - Metabolism of N-[4-chloro-2-fluoro-5-[(1-methyl-2-propynyl)oxy]phenyl]-3,4,5,6-
      tetrahydrophthalimide (S-23121) in the rat. II. Absorption, disposition,
      excretion and biotransformation.
AB  - 1. To examine the metabolic fate of N-[4-chloro-2-fluoro-5-[(1-methyl-2
      propynyl)oxy]phenyl]-3,4,5,6- tetrahydrophthalimide (S-23121), rats were given a
      single oral dose of [phenyl-14C]S-23121 at 1 or 250 mg/kg. 2. The radiocarbon was
      almost completely eliminated from the rat within 7 days after administration for
      both dose groups. Faecal 14C-excretion was major (71-86% of the dose) and urinary
      14C-excretion was minor (18-30%). 3. 14C-tissue residues on the seventh day after
      administration were generally very low. Peak 14C-concentrations in the kidney and
      liver occurred 4 h after administration and decreased rapidly thereafter. Amounts
      (percentage of dose) of the parent compound in faeces were 13-26% for low dose,
      and 22-35% for high dose. 4. The major metabolites in faeces were sulphonic acid
      conjugates (13-20% of the administered dose), formed by incorporation of a
      sulphonic acid group into the double bond of the tetrahydrophthalimide. The major
      metabolites in urine were sulphates and glucuronides of 4-chloro-2-fluoro-5
      hydroxyaniline, amounting to 5-7 and 2-3% of the administered dose, respectively.
      Sulphonic acid conjugates were not detected in urine, blood, kidney or liver.

PMID- 8259691
TI  - Metabolism of xenobiotics by Beauveria bassiana.
AB  - 1. Diazepam, warfarin and testosterone were metabolized by whole resting cells of
      the fungus Beauveria bassiana IMI 12939 via oxidative reactions such as
      hydroxylation and N-demethylation. 2. Metabolism of each substrate was inhibited
      by the cytochrome P450 inhibitors SKF-525A and metyrapone, consistent with the
      involvement of this enzyme system in the metabolism of these drugs by B.
      bassiana. 3. Substrate concentration-dependent inhibition was observed during
      diazepam metabolism by this organism, as has been observed in some mammalian
      systems. 4. Unlike most mammalian P450 systems, the warfarin-metabolizing
      activity of B. bassiana could not be induced by growing the organism in the
      presence of phenobarbitone, beta-naphthoflavone, 3-methylcholanthrene, 1
      benzylimidazole or warfarin. 5. Overall findings indicate that B. bassiana
      possesses an oxidative metabolizing system capable of producing metabolites found
      in mammalian systems.

PMID- 8259692
TI  - In vitro hepatic biotransformation of moclobemide (Ro 11-1163) in man and rat.
AB  - 1. Moclobemide, an inhibitor of monoamine oxidase, shows mixed MAO A/B inhibition
      in rat, but pure MAO A inhibition in man. This is attributed to a primary amine
      metabolite which inhibits MAO B in vitro, but which is not detected in human
      plasma in vivo. A secondary amine metabolite, also present in rat but not human
      plasma, inhibitors MAO B in vivo but not in vitro. 2. We have studied the
      biotransformation of moclobemide in vitro, to investigate whether hepatocytes and
      hepatic subcellular fractions can reproduce the in vivo interspecies differences.
      3. Moclobemide was more extensively metabolized by rat liver preparations,
      compared with man. For example, of an initial 100 nmol, 78 and 25 nmol were
      metabolized within 24 h by rat and human hepatocytes in primary culture,
      respectively. 4. Substantial amounts of secondary amine (12.5 nmol) were found
      with the rat preparation, compared with low amounts (1.5 nmol) from human
      hepatocytes. Similarly, for the primary amine, 1.5 nmol were formed by the rat
      hepatocytes compared with trace amount in the human preparations. 5. Identities
      of the two amines were confirmed by h.p.l.c. cochromatography and negative CI GC
      MS. 6. In conclusion, all the in vitro models, but particularly hepatocytes,
      reflected the metabolism of moclobemide in vivo. Consequently, liver preparations
      can be used prospectively to screen the selectivity of related development
      compounds.

PMID- 8259693
TI  - Toxicokinetics and metabolism of linuron in rabbit: in vivo and in vitro studies.
AB  - 1. Linuron (N'-(3,4-dichlorophenyl)-N-methoxy-N-methylurea) metabolism and
      kinetic behaviour were investigated after oral and i.v. administration to six New
      Zealand White female rabbits. 2. After i.v. dosage, linuron distributes quickly
      and widely to peripheral tissues and its is rapidly eliminated; rapid absorption
      was also observed after oral administration of the herbicide which undergoes
      extensive first pass metabolism in the liver. 3. The major metabolites obtained
      from both in vivo (serum samples) and in vitro (microsomal fractions incubated
      with linuron) experiments were identified by h.p.l.c.-mass spectrometry as N'
      (3,4-dichlorophenyl)-N-methoxyurea, N'-(3,4-dichlorophenyl) urea, and N'-(6
      hydroxy-3,4-dichlorophenyl) urea. 4. Given the common metabolites reported in rat
      and rabbit, and the fact that linuron is a liver enzyme inducer in rat, it may be
      possible that linuron also induces the P450 system in rabbit. Hence, despite the
      low acute toxicity of linuron in rabbit, the intake of hay and feed contaminated
      by the herbicide could be a health risk for these breeding animals since it could
      modify the effectiveness of many drugs commonly used in veterinary practice and
      metabolized by the same liver enzymes.

PMID- 8259694
TI  - Differences in the induction of carboxylesterase isozymes in rat liver microsomes
      by perfluorinated fatty acids.
AB  - 1. Differences in the ability of metabolically-inert peroxisome proliferators
      (perfluoro-n-decanoic acid (PFDA, C10), perfluoro-n-octanoic acid (PFOA, C8),
      perfluorooctane sulphonic acid (PFOS, C8) and 1-H,1-H-pentadecafluoro-n-octanol
      (PFOL, C8)) to induce three forms of hepatic microsomal carboxylesterase, namely
      RL1, RL2 and RH1, in the male rat were studied by measuring changes in hydrolytic
      activities towards p-nitrophenyl acetate (PNPA), isocarboxazid (ISOC) and
      butanilicaine (BUTA), which are thought to be specific substrates for RL1, RL2
      and RH1, respectively, and by evaluating changes in the contents of the three
      isozymes by radial immunodiffusion assay with specific antibodies. 2. The
      administration of PFDA rather specifically decreases PNPA hydrolase activity and
      RL1 content. On the other hand, PFOA, PFOS and PFOL markedly increase all three
      hydrolase activities and the content of all three isozymes (except RH1 in the
      case of PFOA, where the increase was not statistically significant). 3. The
      correlations between hydrolase activities and isozyme contents supported
      specificity of the three substrates, with the exception that the content of the
      predominant isozyme, RL2, showed a higher correlation with BUTA hydrolase
      activity than with ISOC hydrolase activity. 4. In conclusion, we have
      demonstrated that metabolically-inert perfluorinated fatty acids induce hepatic
      microsomal carboxylesterase isozymes, as determined by radial immunodiffusion
      analysis using specific antibodies. This is the first report that perfluorinated
      fatty acid affect carboxylesterase isozymes in rat liver microsomes, and is
      indicative of the importance of peroxisome proliferators in hepatic metabolism of
      xenobiotics. Further work is needed to determine the regulatory mechanisms
      involved.

PMID- 8259695
TI  - Correlation between site specificity and electrophilic frontier values in the
      metabolic hydroxylation of biphenyl, di-aromatic and CYP2D6 substrates: a
      molecular modelling study.
AB  - 1. A series of biphenyl, di-aromatic and CYP2D6 substrates known to undergo
      metabolic aromatic hydroxylation was derived from the literature, several animal
      species were represented. 2. Molecular orbital calculations were performed on the
      substrates using the AM1 semi-empirical force field and the electrophilic
      frontier values (f(E)) plotted for each available aromatic site. 3. A qualitative
      correlation was observed between the sites of oxidation and high f(E) values,
      suggesting the role of frontier orbitals in the metabolic hydroxylation of these
      substrates. 4. The mechanistic implications for the involvement of frontier
      orbitals in aromatic hydroxylation are discussed. It is proposed that electron
      abstraction occurs in the region of high electron density to form a radical
      cation. Hydrogen abstraction by Fe++O- then occurs followed by oxygen rebound. 5.
      The method can be helpful in indicating regio-specificity in the metabolic
      hydroxylation of bi-phenyls, related di-aromatic compounds and possibly CYP2D6
      aromatic substrates.

PMID- 8259696
TI  - Assessment of drug exposure in rat dietary studies.
AB  - 1. The objective of this study was to justify the evaluation of exposure of
      animals to chemical substances on the basis of only three blood samples taken
      during a 24-h period, but still with acceptable accuracy. 2. Fischer rats were
      fed a diet mixed with either paracetamol, 100 mg.kg-1 (short half-life compound),
      antipyrine, 100 mg.kg-1 (medium half-life compound), or phenylbutazone, 50 mg kg
      1 (long half-life compound) for 3 weeks. It had been shown in a preliminary study
      that these compounds when administered at these dose levels did not influence
      feeding behaviour. At the end of 3 weeks, five rats were sampled every 3 h
      beginning and ending at 19.00 h (45 rats in total) and plasma concentrations were
      measured using h.p.l.c. 3. The area under the curve over 24 h (AUC24), calculated
      using all nine concentrations was considered to be the true AUC24. Subsequently,
      estimates of this parameter were made using different combinations of
      concentrations at three or even two selected time points. 4. For each compound,
      the highest concentration occurred at 07.00 h. It was shown that using the
      concentrations at 07.00, 10.00 and 16.00 h the estimate of the AUC24 was within
      15% of the true value. 5. In comparison with a gavage study in the same rat
      (strain and age), bioavailability was lower in the diet study with relative
      bioavailabilities of 27, 22 and 61% for paracetamol, antipyrine and
      phenylbutazone, respectively. 6. In conclusion, drug exposure as expressed by
      AUC24 and Cmax can be accurately determined in rat studies using compound
      administration in the diet by measuring concentrations at three selected time
      points for compounds with elimination half-lives ranging from about 1 to 5 h.

PMID- 8259697
TI  - New therapeutic techniques and strategies in pulmonary rehabilitation.
AB  - Patients with chronic obstructive pulmonary disease (COPD) or those with
      paralytic restrictive pulmonary syndromes caused by progressive neuromuscular
      disease, kyphoscoliosis or traumatic quadriplegia may require frequent
      hospitalization because of respiratory impairment and have increased morbidity
      and mortality. Pulmonary rehabilitation has been shown to decrease the frequency
      of hospitalization, ameliorate symptoms, increase exercise tolerance, and in one
      study, prolong life for individuals with COPD. It is now recognized that
      principles of pulmonary rehabilitation can also be used to avoid hospitalization,
      intubation, tracheostomy and bronchoscopy while enhancing quality of life,
      decreasing cost, and greatly prolonging life for individuals with paralytic
      restrictive syndromes and global alveolar hypoventilation as well.

PMID- 8259698
TI  - Smoking and total mortality: Kangwha cohort study, 6-year follow-up.
AB  - The relationship between smoking and total mortality was examined in a community
      residents population sample of 2,848 men and 3,543 women aged 55 years or over in
      Kangwha County, Korea during 1985-1991. A total of 1,436 deaths occurred during a
      6-year follow-up among the 1.3 fold-higher in current smokers than in non-smokers
      among men. The relative risk of total mortality was highest for the 55-59 year
      old age group both in ex-smokers and in current smokers. PAR for total mortality
      attributed by smoking were estimated to be 26% for ex-smokers and 25% for current
      smokers in men. The biggest RR (2.1) and PAR (49%) were observed among those who
      smoked less than 19 cigarettes per day compared to non-smokers in males. Smokers
      who began to smoke at age 18 or before showed RR 1.8, and PAR 38% in men. Smoking
      was the most important variable related with total mortality second only to
      hypertensiveness not including preventable ones among men in multivariate
      analyses. Men who began to smoke at nineteen years of age or before had RR 1.5
      for total cancer mortality. Women showed the similar picture as males in risk
      factors composition and in relative risks, with a low association strength,
      however.

PMID- 8259699
TI  - The effect of smoking on health service utilization.
AB  - This study involved direct observation of the differences in prevalence of
      disease and utilization of medical care by smokers, non-smokers, and ex-smokers.
      The data was collected from the 1989 Korean National Health Survey (1989 KNHS). A
      total of 5,201 individuals ages 20 to 59 were randomly selected from the whole
      Korean population using the three-stage stratified random sampling. Based on the
      logistic regression, the following results were obtained. Compared with the non
      smokers, the relative risks for an acute disease were 1.9 and 1.7 for male ex
      smokers and female current smokers, respectively. Smoking behavior significantly
      increased utilization of health services such as admissions (RR = 2.5 for current
      smokers) among females, outpatient visits (RR = 2.1 for ex-smokers, RR = 2.3 for
      age began to smoke was less than 18 years) among males and (RR = 1.5 for current
      smokers) among females. Furthermore, the utilization of outpatient services for
      ex-smokers who were self-concerned about their health was 3.4 times higher than
      the non-smokers. Based on the weighted least square regression model the days of
      medication for male current smokers and ex-smokers were significantly longer than
      non-smokers. These effects persisted after controlling for major identified
      confounding factors. Thus, the results of this study confirmed that smoking is an
      important cause of diseases and a major contributing factor to the use of health
      services.

PMID- 8259700
TI  - The fibrinogen degradation products (FgDP) levels in liver disease.
AB  - We measured plasma levels of fibrinogen degradation products (FgDP) with newly
      developed enzyme-linked immunosorbent assay based on monoclonal antibody to
      assess the fibrinogenolytic state in 52 patients with various liver diseases (27
      patients with liver cirrhosis, 10 with chronic hepatitis, 7 with acute hepatitis,
      6 with hepatocellular carcinoma, 2 with intrahepatic cholestasis). As compared
      with 20 healthy subjects (upper limit: 580 ng/ml), elevated plasma levels (660
      32000 ng/ml) of FgDP were found in 19 (36.5%) patients. When analyzed according
      to the underlying disease categories, the magnitude of elevations of FgDP were
      most prominent in patients with chronic hepatitis. No correlation was found
      between plasma FgDP levels and serum AST or ALT activity. These findings indicate
      that increased primary fibrinogenolysis is not rare in liver disease, but poorly
      correlates with liver function.

PMID- 8259701
TI  - Percutaneous mitral balloon valvuloplasty in patients with restenosis after
      surgical commissurotomy: a comparative study.
AB  - We performed percutaneous mitral balloon valvuloplasty (PMV) in 367 patients to
      compare the effectiveness of PMV between patients with mitral restenosis after
      surgical commissurotomy (group 1) and patients with unoperated mitral stenosis
      (group 2). Twenty-two had undergone closed or open mitral commissurotomy 11.2
      years before. There were no significant differences in clinical profiles between
      the two groups. The mitral valve area was increased from 1.0 +/- 0.8 to 1.8 +/-
      0.6 cm2 in group 1 and 0.9 +/- 0.3 to 2.0 +/- 0.7 cm2 in group 2 (p > 0.05). The
      mitral gradient was decreased from 14 +/- 5.9 to 6 +/- 2.6 mmHg in group 1 and 18
      +/- 7.0 to 7 +/- 5.3 mmHg in group 2 (p > 0.05). The increment of mitral
      regurgitation and significant left to right shunt after PMV were not
      significantly different (10% versus 14.7%, 5% versus 10.4% respectively). Optimal
      results were attained in 75% of the patients in group 1 and in 84.3% of the
      patients in group 2 (p > 0.05). These results suggest PMV in mitral restenosis
      after surgical commissurotomy may be safe in selected patients and may be equally
      effective as in unoperated mitral stenosis.

PMID- 8259702
TI  - Detection of specific serum IgE in clonorchiasis cases and analysis of Clonorchis
      sinensis allergens.
AB  - Specific serum IgE levels of Clonorchis sinensis in infected humans were measured
      by avidin-biotin ELISA, and allergens from C. sinensis were identified by
      immunoblot and autoradiography. Then, allergens fractionated by Sephadex G-200
      gel filtration were analyzed, and cross-reactive allergenic components of C.
      sinensis reacted with paragonimiasis sera were revealed. Fourteen out of 15 C.
      sinensis egg-positives were found to be serum IgE positive (absorbance > 0.27).
      Of 14 IgE-reacting allergen bands visualized, major allergens of 66, 61.5, 45,
      37, 28.5, 23.5 and 15.5 KD were recognized by more than 50% of the sera of
      infected humans. The considerable individual variations of IgE immune responses
      to C. sinensis allergenic components were also noticed. C. sinensis extract was
      separated into 5 fractions by Sephadex G-200 gel filtration. Seventy-four KD
      allergen was recognized in the first fraction, 50, 45, 37, 29.5 and 28.5 KD in
      the third, and 15.5 KD in the fourth. Cross-reactive allergens with sera of
      paragonimiasis cases were identified as 66, 45, 28.5, 13 and 7.5 KD.

PMID- 8259703
TI  - Effect of polyadenylic.polyuridylic acid on cellular responses of peripheral
      blood mononuclear cells from patients with chronic active hepatitis B.
AB  - We have investigated in vitro proliferative responses of peripheral blood
      mononuclear cells and productions of interferon-gamma and soluble interleukin-2
      receptors by these cells from 6 patients with chronic active hepatitis B
      immediately before and 24 hours after a single intravenous injection of 100 mg of
      polyadenylic.polyuridylic acid. Cell proliferations were assessed by the
      technique of tritiated-thymidine incorporation and productions of interferon
      gamma and soluble interleukin-2 receptors were measured by enzyme-linked
      immunosorbent assay. The administration of polyadenylic.polyuridylic acid to the
      patients has resulted in significant increases of in vitro proliferations of
      their peripheral blood mononuclear cells as well as productions of interferon
      gamma by these cells. However, in vitro productions of soluble interleukin-2
      receptors were not changed significantly. These results suggest that the enhanced
      cellular responses by polyadenylic.polyuridylic acid might be due to the
      increased sensitivity rather than the increased expression of cellular
      interleukin-2 receptor.

PMID- 8259704
TI  - Regional differences in the levels of biogenic amines and their metabolites in
      rat brain after tricyclic antidepressant treatments.
AB  - Changes in the levels of biogenic amines in different brain regions and the
      cerebrospinal fluid in rats were measured after acute or chronic treatment with
      tricyclic antidepressants. After single or 3 weeks' treatment with imipramine or
      desipramine, blocks of tissues were obtained from seven regions of the brain
      (frontal cortex, corpus striatum, hippocampus, thalamus, hypothalamus, substantia
      nigra and cerebellum) immediately after collection of the cerebrospinal fluid
      (CSF) from the cisterna magna. The concentrations of biogenic amines and their
      metabolites (norepinephrine, epinephrine, dopamine, 5-hydroxytryptamine (5-HT),
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5
      hydroxyindoleacetic acid (5-HIAA)) in brain tissues and the CSF were measured
      using the high performance liquid chromatography-electrochemical detection system
      (HPLC-ECD). Treatment with desipramine or imipramine caused major alterations in
      the concentrations of central norepinephrine or 5-HT and its metabolite,
      respectively. Brain regional responses were variable according to the kind of
      tricyclic antidepressants and the duration of treatment. It is noteworthy that
      chronic treatment with both desipramine and imipramine caused altered hippocampal
      concentrations of norepinephrine and/or 5-HT and its metabolites. Striatal DOPAC
      concentrations were also changed after acute or chronic treatment with both
      drugs. These results suggest that tricyclic antidepressants altered
      neurotransmission according to the brain region, and the hippocampal
      norepinephrine and 5-HT and/or the striatal dopamine may have a significant role
      for the expression of antidepressant action of tricyclic antidepressants.

PMID- 8259705
TI  - Effect of wheelchair ergometer training on spinal cord-injured paraplegics.
AB  - The purpose of this study was to investigate the effect of wheelchair ergometer
      training on spinal cord-injured paraplegics. Eleven male paraplegics with a mean
      age of 30.9 years (range, 20 to 49 years) participated in the wheelchair
      ergometer training for the period of 5 weeks. The mean peak heart rate, the mean
      peak systolic blood pressure and the mean time required for 100m wheelchair
      propelling at resistance level 1 were significantly decreased at the end of 5
      weeks of training as compared with those at pre-training. There was no
      statistically significant difference in pulmonary function test at pre- and post
      training. The peak torque of shoulder flexor and the total work of shoulder
      flexor and extensor at 180 degrees/sec after training were increased more
      significantly than those prior to the training. In accordance with the findings
      as revealed above, it is deemed that the endurance and strength of the upper body
      and the cardiac fitness for spinal cord-injured paraplegics may be improved by
      the wheelchair ergometer exercise.

PMID- 8259706
TI  - Adenocarcinoma of the transverse colon in a child with survival--a case report.
AB  - The incidence of carcinoma of the large bowel is very low in children, and it is
      also known that the prognosis of this tumour in children is very poor. Recently
      the authors experienced a case of adenocarcinoma of the transverse colon in a 12
      year old boy who survived more than 6 years without evidence of disease. This
      particular case is reported here with a review of the literature.

PMID- 8259707
TI  - Multiple myeloma and chronic myelogenous leukemia--a case report with literature
      review.
AB  - This is the case of a 71 year old male who developed multiple myeloma (MM) and
      chronic myelogenous leukemia (CML) within a two year period. The patient
      initially presented with osteolytic lesions of the lumbar spine, and following
      the initial work-up a diagnosis of multiple myeloma with an IgG kappa
      paraproteinemia was made and appropriate treatment was given. Two years later the
      patient developed a progressively worsening leukocytosis which was found to be
      due to Philadelphia Chromosome (Ph1) positive CML. The occurrence in the same
      patient of two distinct hematologic malignancies suggests a neoplastic
      transformation of a pluripotent stem cell. A review of the literature appears to
      support the existence of a relationship between MM and CML as well as a
      relationship between MM and the myeloproliferative disorders.

PMID- 8259708
TI  - [Oxygen radicals and cardiovascular diseases: pathogenetic mechanisms,
      therapeutic possibilities].
AB  - "Oxygen radicals" is a term used as a synonym for a group of reactive radical and
      non-radical species formed by successive univalent reduction of oxygen,
      interaction of the primarily formed oxygen radicals and by reaction of oxygen
      radicals with other molecules and ions of the biological system e.g.
      polyunsaturated fatty acids and halogenides. Besides physiological reactions
      (metabolism of xenobiotics and arachidonic acid; phagocytosis), the high
      reactivity of oxygen radicals leads also to unspecific reactions with
      biomolecules resulting in cell damage. In the last fifteen years, the
      participation of oxygen radical induced processes of damage (lipid peroxidation,
      thiol group oxidation, Schiff bases formation) in the pathogenesis of chronic and
      acute diseases of the heart and circulatory system was studied extensively. This
      review summarizes essential results of in vitro, animal and clinical studies
      including our own investigations on the biochemical basis between oxygen radical
      dependent cell damage and the relation between oxygen radical formation and the
      development of diseases in the heart and circulatory system (atherosclerosis,
      myocardial ischemia and reperfusion). Open questions concerning the causes of
      enhanced formation and diminished inactivation of oxygen radicals and
      pathogeneticly important targets of oxygen radicals in the heart and circulatory
      system are discussed.

PMID- 8259709
TI  - [Intravascular ultrasound in peripheral calcified vascular lesions: comparison
      with direct magnification radiography].
AB  - Intravascular ultrasound can detect calcified peripheral arteriosclerotic lesions
      by hyperdense echo patterns and shadowing of subintimal layers. Nevertheless, 20
      MHz ultrasound systems have not been validated for the detection of peripheral
      calcifications; besides, it is unknown whether the depiction of calcified lesions
      by intravascular ultrasound depends on the morphology of the calcification.
      Histological evaluation of severely calcified arteries is difficult because the
      preparation of those specimens often causes artefacts, e.g., fracture of
      calcified structures. Direct magnification radiography, currently used in
      forensic medicine or skeleton examination, is based on a minimized focus and
      enables the edge-enhanced views of calcifications with high discrimination. In
      this in-vitro-study direct radiological magnification was used to validate
      intravascular ultrasound. Forty-nine segments of human peripheral arteries were
      fixed in formalin, examined with intravascular ultrasound and, as a reference,
      radiographically magnified using a newly developed microfocus x-ray tube.
      Sensitivity, specificity, positive and negative predictive value, and accuracy of
      intravascular ultrasound for the detection of calcified wall areas were
      determined and compared to the appearance (configuration, circumferential and
      areal expansion, density, number of fragments) of these calcifications.
      Thicknesses of 110 single calcified structures were estimated on sonograms and
      radiograms. The overall sensitivity of the 20 MHz intravascular ultrasound system
      for the detection of calcification in 913 sectors was 70%, specificity 53%,
      positive predictive value 66%, negative value 58% and accuracy 62%. The depiction
      of calcified regions by direct magnification radiography showed that the
      sensitivity strongly depended on the density of the calcification. Sensitivity
      was 81% with calcified lesions of high density, but only 51% with lesions of low
      density.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259710
TI  - [In vitro diagnosis of coronary plaque morphology with intravascular ultrasound:
      comparison with histopathologic findings].
AB  - The aim of this study was to validate the accuracy of a commercially available
      intravascular ultrasound system in diagnosing plaque composition in human
      coronary arteries. Thirty-five coronary arteries of 18 human autopsy hearts were
      perfused with NaCl under a pressure of 100 mmHg and examined using a Diasonics
      ultrasound system and 4.8 F 20 MHz catheters. An ultrasound diagnosis was made of
      139 coronary sections using previously published standard criteria and compared
      with histologic findings. In addition, the influence of the histologic pattern of
      lipid and calcific deposits on the accuracy of the ultrasound diagnosis was
      evaluated. Of the 25 sections with a histologically normal intima, 14 (56%) were
      correctly identified by ultrasound, whereas fibrotic thickening was diagnosed in
      the remaining 11 sections. There were 114 plaques by histology which were
      correctly visualized by ultrasound as plaques in all instances. Plaque
      calcification was correctly diagnosed in 54 of 63 (86%) sections, but massive
      calcifications were more reliably identified by ultrasound than small speckled
      calcifications (43/44 = 98% vs 11/19 = 58%, p < 0.001). Fibrosis was present in
      all 114 plaques and was correctly visualized by ultrasound in all instances. When
      lipid was diagnosed by ultrasound as a homogeneous zone of low signal intensity
      within a fibrous plaque as suggested in the literature, lipid accumulations were
      identified with a sensitivity of 26% (16/62) and a specificity of 92% (71/77).
      When lipids were diagnosed if more than a quarter of the plaque area showed lower
      signal intensity than the tissue surrounding the vessel, the sensitivity of
      ultrasound was improved to 73% (45/62) but specificity fell to 30% (23/77). The
      entire histologic composition of a section was correctly diagnosed by ultrasound
      in only 42% of the 139 sections. Further technical improvements are therefore
      mandatory before intracoronary ultrasound will be able to provide a reliable
      analysis of plaque composition, especially of the lipid content.

PMID- 8259711
TI  - [Multivariate analysis of prognostically significant parameters in acute
      transmural myocardial infarct].
AB  - The clinical data of 722 patients admitted for acute myocardial infarction to the
      coronary care unit of the Hannover Medical School were retrospectively analyzed.
      Six hundred patients survived through the fifth day of their hospital stay. We
      evaluated 142 variables from each patient, i.e., previous cardiac manifestations,
      drug-history, acute complications, laboratory data, intensive care treatment and
      the 1-year outcome. One-hundred-sixty-nine patients underwent cardiac
      catheterization before being discharged from the hospital. Thirty-two variables
      showed to be predictive of 1-year survival in the univariate analysis, although
      performance of logistic regression analysis revealed only seven parameters to be
      independent predictors: age (p < 0.0001), glycoside intake before infarction (p =
      0.0317), acute heart failure (p = 0.0005), late (occurring after 48 h)
      ventricular tachycardia or fibrillation (p = 0.0003), maximum of serum creatine
      phosphokinase (p = 0.0129), new onset of atrial fibrillation (p = 0.0116), and
      use of dobutamine during intensive care stay (p = 0.0014). With this combination
      of clinical variables alone, using a survival probability partition value of 50%,
      the model had a sensitivity of 39% and a specificity of 96%, respectively, 84%
      overall correct classification. Predictive accuracy for death was 71%, compared
      to a predictive accuracy for survival of 85%. Diagnostic procedures performed
      after infarction were highly predictive in the individual case, but they could
      not improve accuracy of the statistical model. These data emphasize the
      importance of multivariate methods to find suitable predictors for outcome after
      acute myocardial infarction.

PMID- 8259712
TI  - Granulocyte elastase in acute myocardial infarction.
AB  - Plasma concentrations of polymorphonuclear granulocytes elastase (PMN elastase)
      in complex with alpha-1 proteinase inhibitor are a marker of neutrophil
      activation. The latter complex, creatine kinase and cardiac troponin T, were
      measured in peripheral venous blood samples serially drawn in 39 patients with
      acute myocardial infarction. Of the total, 29 received intravenous thrombolytic
      therapy either with streptokinase (n = 15), urokinase (n = 7) or recombinant
      tissue type plasminogen activator (n = 7). Creatine kinase activities and cardiac
      troponin T concentrations were used as markers of myocardial tissue injury. In
      all patients with acute myocardial infarction, PMN elastase was elevated (median
      80 micrograms/l, interquartile range 71 to 100 micrograms/l). Peak and cumulative
      (area under curve) concentrations of PMN elastase did not correlate closely with
      determinants of myocardial injury (r < 0.2, n.s.). PMN elastase increased during
      the first 6 h after starting thrombolytic therapy, whereas it decreased in
      conventionally treated patients and 12 h later increased. Maximum concentrations
      of PMN elastase, however, were not significantly higher in patients with
      thrombolytic therapy than in those without. In acute myocardial infarction
      patients with complications such as cardiac arrest with subsequent resuscitation
      (n = 5), cardiac rupture (n = 1) or cardiogenic shock (n = 2), PMN elastase
      plasma concentrations were significantly higher (p = 0.04) than in uncomplicated
      infarctions. In the complicated patients, changes in elastase concentrations
      paralleled or even preceded changes in the clinical presentation. Therefore,
      thrombolytic treatment seems not to significantly influence the amount of
      systemic neutrophil activation, but plasma PMN elastase could be a useful marker
      to monitor and identify complications in acute myocardial infarction.

PMID- 8259713
TI  - [Induction of the atrial and ventricular ANF synthesis in experimental heart
      failure after aortocaval shunt].
AB  - Using the aortocaval shunt as a model of chronic volume overload in the rat,
      changes of the ANF system were analyzed. A constant shunt volume of 57% increased
      the heart weight after 14 days by 28% (from 917 +/- 16 to 1177 +/- 28 mg, p <
      0.001). The ANF plasma concentration increased from 30.4 +/- 15.1 to 108.2 +/-
      30.6 pg/ml (p < 0.05), which corresponds to levels which are reached in early
      stages of heart failure. ANF tissue concentrations, however, were decreased in
      both atria while no significant change could be observed in the ventricles. The
      analysis of the ANF-mRNA expression as an indicator for the ANF-synthesis showed
      significant increase in the ANF-mRNA/Actin-mRNA ratio in the right atrium by 56%
      and in the left atrium by 63%. In ventricular tissue the relative ANF-mRNA
      increased by 58% (right) and 83% (left ventricle). Increased ANF plasma levels
      during chronic volume overload are due to increased atrial and ventricular ANF
      synthesis. The induced ventricular mRNA indicates the participation of the
      ventricles in the humoral response to volume overload.

PMID- 8259714
TI  - [Mitral valve endocarditis caused by Salmonella enteritidis].
AB  - The epidemiology of salmonellosis has undergone a change during the last 2 years.
      An increase in the number of cases of enteritis and sepsis caused by Salmonella
      enteritidis has been observed. We report on the case of a 65-year-old woman with
      mitral valve endocarditis due to Salmonella enteritidis. The infective
      endocarditis occurred without prior episodes of gastroenteritis. After having
      undergone prosthetic valve replacement and antibiotic therapy with ciprofloxacin,
      the patient recovered completely.

PMID- 8259715
TI  - [Recurrent myxoma].
AB  - In a now 53-year-old woman, who suffered from recurrent syncope and dizziness, a
      biatrial myxoma originating from the interatrial septum was resected nearly 4
      years ago, and the resulting septal defect was closed by a Dacron patch. In the
      symptomless patient the recurrent myxoma was revealed by echocardiography. The
      left atrial myxoma was surgically removed without repeat heart catheterization.
      This case underlines the importance of regular, echocardiographic follow-up
      examinations in patients in whom a myxoma has been excised. In case of suspicious
      findings, an additional transesophageal examination or nuclear magnetic resonance
      imaging should be performed.

PMID- 8259716
TI  - [Jo-1-(antisynthetase-) syndrome--do autoantibodies improve classification of
      myositis?].

PMID- 8259717
TI  - [Pseudo-natural treatment and alternative methods in rheumatology].
AB  - In rheumatology, besides generally acknowledged so-called "natural treatment"
      methods, disputed and non-suitable methods are alleged as being also "natural
      methods". In particular, it is the "Action for Biological Medicine" which strives
      against any necessity of a differentiated approach on the basis of the benefit
      risk relation. In this paper, after a short introduction covering the present
      legal situation in Germany, examples of unconventional diagnostic and therapeutic
      methods are discussed. Since the alleged benefit of these methods has never been
      proved, they must without any exception be considered as totally unnecessary.
      Moreover, because of the high risk involved, some methods must be warned against.
      Instead, demonstrably successful psychological and behavior-therapeutic methods
      should be recommended, the more so, as these can assist patients in becoming
      independent.

PMID- 8259718
TI  - [Nutrition as adjuvant therapy in chronic polyarthritis].
AB  - In the literature many casual observations report an arthritogenic effect of
      individual nutrients. The discovery of eicosanoids derived from arachidonic acid
      (AA) as most relevant mediators of joint inflammation allowed to elaborate the
      basis for a dietary therapy of rheumatoid arthritis. With an average intake of 18
      g/d linoleic acid in western societies, linoleic acid is not converted to AA, and
      plasma levels of AA depend on its dietary intake with meat or meat products. The
      amount of AA ingested with the diet correlates with the formation of
      proinflammatory eicosanoids. Additionally, AA levels can be lowered by the
      ingestion of fish oil fatty acids. In our experiment, we aimed to combine the
      effect of low AA intake with the known anti-inflammatory effect of fish oil fatty
      acids. Our results demonstrate that vegetarians have lower AA percentages in
      erythrocyte lipids compared to the control group. The lower AA levels in plasma
      lipids coincided with higher percentages of fish oil fatty acids after
      supplementation, resulting in lower formation of mediators of inflammation.
      Moreover, the vegetarian group experienced a more pronounced decrease of AA in
      erythrocyte lipids after supplementation with fish oil fatty acids. These effects
      are supposed to contribute to the more favorable clinical course and laboratory
      findings in patients with rheumatoid arthritis on a vegetarian diet.

PMID- 8259719
TI  - [Epidemiology of rheumatic complaints in Germany. Data on the prevalence and
      physical and psychosocial disability].
AB  - Because of their considerable socioeconomic costs rheumatic symptoms are a major
      concern in industrialized nations. Our study provides data on the prevalence of
      rheumatic symptoms in the general population and on their physical and
      psychosocial impact. We performed a survey of 1814 randomly selected non
      institutionalized persons, aged 40 to 69 years, living in the Federal Republic of
      Germany. The selected subjects were asked whether they had pain in one or more of
      the following sites: neck/back, joints of upper extremities, joints of lower
      extremities. Physical and psychosocial disability was assessed using a
      multidimensional questionnaire that included a German version of the Arthritis
      Impact Measurement Scales (AIMS) and validated instruments concerning
      psychosocial dimensions of health status. The prevalence of rheumatic symptoms
      increases between 40 and 59 years and decreases thereafter. Rheumatic symptoms
      are more frequent in women than in men. The predominant pain localization is the
      back. Individuals reporting pain in one region (back, upper and lower
      extremities) often feel pain in other areas as well and often suffer from
      additional symptoms such as weakness and sleep disturbance. We found significant
      disabilities in physical (mobility, activities of daily living, physical
      activities) and psychosocial (depression, anxiety, exhaustion, family problems)
      dimensions of health status in subjects reporting rheumatic symptoms.

PMID- 8259720
TI  - The influence of heat and cold on the pain threshold in rheumatoid arthritis.
AB  - Superficial heat and cold are commonly used therapeutic methods in patients with
      rheumatoid arthritis. Both procedures have analgesic effect. In 30 inpatients
      with rheumatoid arthritis the pain threshold was measured before and after warm
      bath and ice massage. Rheumatoid patients had significantly lower pain threshold
      compared to the healthy subjects in normal circumstances. Heat and cold
      remarkably raise the pain threshold right after the application. The pain
      threshold is also raised 10 and 30 min after cryotherapy, but not after the warm
      bath. Between investigated groups there were no statistically significant
      differences in the pain threshold values in any observed time. We consider that
      both methods have a reasonable place in the therapy of rheumatoid arthritis.

PMID- 8259721
TI  - Combination therapy with hydroxychloroquine and methotrexate in rheumatoid
      arthritis.
AB  - The aim of the study was to compare the efficacy of hydroxychloroquine (HCQ)
      alone and in combination with methotrexate (MTX) in a randomized placebo
      controlled study lasting 6 months. Forty patients with rheumatoid arthritis
      participated in the study and were randomly assigned to two groups--20 patients
      were treated with HCQ (200 mg daily) and placebo, 20 patients with HCQ and MTX
      (7.5 mg) once a week. Patients were assessed at regular intervals of 1 month up
      to 6 months using six clinical and five laboratory tests and one radiological
      measure. All six clinical variables and two laboratory variables were favorably
      influenced by combination therapy during the 6-month period. HCQ alone
      significantly influenced only three clinical variables and none of the laboratory
      parameters. There was a greater number of patients without radiological
      progression in the combination group. There was one drop-out in combination group
      due to general allergic reaction; otherwise the treatment was well tolerated. The
      results suggest that a combination of HCQ and MTX is more potent than HCQ alone.

PMID- 8259722
TI  - [Polymyositis and Jo-1 syndrome].
AB  - Polymyositis is a primarily clinical diagnosis. In 30-40% of patients, however,
      the specific anti-Jo-1 antibody (anti-histidyl-tRNA-synthetase) can be found.
      These cases are often associated with interstitial lung disease and other typical
      clinical manifestations. This symptomatology is called Jo-1-syndrome. Prognosis
      depends on early diagnosis, since Jo-1 associated interstitial lung disease
      resulting in pulmonary fibrosis is favorably influenced by immunosuppressive
      therapy, especially with corticosteroids. The present report concerns a patient
      with Jo-1-syndrome and beginning pulmonary fibrosis who was treated with
      methotrexate and prednisolone with good initial response. After 1 year the
      patient's condition had deteriorated, so that the therapy was changed to
      cyclophosphamide. Longterm results under this therapy remain to be evaluated.

PMID- 8259723
TI  - Interstitial alveolitis as early manifestation of anti-Jo-1 positive
      polymyositis.
AB  - Polymyositis (PM), dermatomyositis (DM) and inclusion-body myositis belong to a
      heterogenous group of inflammatory myopathies. Pulmonary manifestations occur in
      a minority of PM patients due to infiltration of diaphragmatic and thoracic
      muscles or more rarely due to interstitial lung disease. Here, we report on the
      case of a 67-year-old patient who developed an interstitial idiopathic alveolitis
      as an early and rare manifestation of anti-Jo-1-positive polymyositis. Clinical
      and pathogenetical features of the PM associated interstitial alveolitis are
      discussed.

PMID- 8259724
TI  - [Anesthesia in minimally invasive surgery--is anesthesiologic practice also
      changing?].

PMID- 8259725
TI  - [Anesthesiologic aspects of minimally invasive surgery].
AB  - Minimal invasive, or more specifically laparoscopic surgery is now the standard
      procedure in an increasing number of surgical specialties. Inflating the abdomen
      with CO2 for long periods confronts the anesthesiologist with a number of
      problems that influence the choice of anesthetic and the monitoring deemed
      necessary. The increased intraabdominal pressure (IAP) and for some operations
      the extreme Trendelenburg position can disturb alveolar ventilation and
      compromise oxygenation. Pulse oximetry is therefore required to recognize and
      counteract these effects. The insufflated CO2 is absorbed into the blood to an
      unpredictable extent, and must be eliminated via the lungs by increasing the
      minute ventilation. Only capnometry or serial blood gas analyses can provide the
      information needed to correctly adjust the respiration. The endocrine stress
      reactions to laparoscopic surgery do not appear to be less pronounced than after
      conventional operations; only the interleukin-6 response to laparoscopic
      cholecystectomy is reduced compared to the subcostal incision. But minimal
      invasive surgery offers an advantage at least for cholecystectomy in that there
      is less impairment of postoperative respiratory function. General anesthesia will
      be the method of choice for laparoscopic surgery in all but a few procedures in
      which regional anesthesia is an acceptable alternative. Balanced anesthesia or
      total intravenous anesthesia is to be preferred, and the drugs employed should
      have rapid elimination kinetics with a short recovery time, since wound closure
      time is drastically reduced. Inhalational anesthesia alone may inhibit hypoxic
      pulmonary vasoconstriction thereby unduly increasing oxygen desaturation. The
      necessary degree of muscle relaxation still remains to be defined.

PMID- 8259726
TI  - [Specifics of anesthesiology in the operative phase of laparoscopic surgery].
AB  - AIM OF INVESTIGATION: The present investigation was initiated to quantify the
      effect of a CO2-peritoneum on CO2-absorption (VCO2res) and other respiratory
      variables during laparoscopic surgical procedures. METHODS: Gas exchange and
      endtidal pCO2 (petCO2) were measured continuously. Ventilation was adjusted to
      maintain preoperative petCO2 mainly by increasing the tidal volume. Arterial
      blood gas samples were taken directly before starting and directly before the end
      of the CO2-peritoneum. RESULTS: In 49 patients a complete set of data was
      evaluated for a mean duration (+/- 50) of 99 (43) min CO2-peritoneum. The mean
      VCO2res was 37 (30)ml/min. The VCO2 showed a steady state of 137 (29)ml/min
      before the start of the operation. Individual VCO2res maxima of 223 ml/min were
      detected. Due to a mean rise of arterial pCO2 (paCO2) of 39 (3.6) to 42.6 (4.5)
      mmHG the VCO2res was underestimated by about 5 ml/min. This CO2 accumulation was
      mainly the result of an increasing petCO2-paCO2 difference till the end of the
      CO2-peritoneum. No significant change in VCO2res has been detected with
      increasing duration of the CO2-peritoneum, though in individual courses a
      continuously increasing VCO2res was found. Overweight individuals (n = 17) showed
      a significantly lower VCO2res of 23 (12)ml/min in comparison to normal weight
      patients (n = 34) with 43 (16)ml/min. The static total compliance was
      significantly reduced by 30% at the end of the CO2-peritoneum. The ventilatory
      deadspeace/tidal volume relation did not change. To maintain normocapnia the
      average alveolar ventilation had to be increased by 38% till the end of the CO2
      peritoneum. CONCLUSIONS: This increase in ventilation can easily be established
      in pulmonary uncompromised patients. Problems in adequately increasing minute
      volume are expected in chronic obstructive lung disease and with maximal VCO2res.
      Monitoring of at least petCO2 is strongly recommended since the individual course
      of VCO2res cannot be predicted.

PMID- 8259727
TI  - [Anesthesiologic aspects of minimally invasive surgery--preoperative assessment].
AB  - Laparoscopic surgery may be associated with increased perioperative morbidity due
      to respiratory and cardiocirculatory problems. Preoperative assessment requires a
      diagnostic program including laboratory tests and noninvasive diagnostic studies,
      and a physical status classification. High-risk patients are those with
      intracardial right-to-left shunts (increased risk of gas embolism) and patients
      in shock. Increased intraoperative morbidity is expected in patients with
      manifest cardiac failure or severely restricted pulmonary function. In patients
      with moderate pulmonary dysfunction laparoscopic procedures seem to be associated
      with the benefit of a better postoperative pulmonary function.

PMID- 8259728
TI  - [Postoperative analgesia--a comparative study in laparoscopic cholecystectomy and
      lower abdominal laparotomy].
AB  - From September 1992 through February 1993 27 randomly chosen female patients were
      evaluated for differences in postoperative pain intensity (as determined by
      visual-analogue-scale (VAS)) and analgesic requirements via patient-controlled
      analgesia (PCA), either after open lower-abdominal-laparotomy (n = 16, group 1)
      or after minimal-invasive-cholecystectomy (n = 11, group 2). The type of
      anaesthesia has been standardized, either as balanced or total intravenous
      anaesthesia. There were no statistically significant differences between the
      groups regarding to age, height, weight, intraoperative anaesthetic drug
      consumption, or duration of anaesthesia and surgery (205.6 vs 185.5 minutes;
      139.1 vs 105.0 minutes). All patients could be extubated while still in the
      operation theatre. The 10-hour study period started after transfer to the
      recovery room. Heart- and respiratory-rate, systolic/diastolic blood pressure,
      endtidal pCO2, oxygen-saturation via pulsoxymetry (SaO2), and demands from PCA
      pump were recorded, furthermore pain scores were determined every hour. The VAS
      scores showed no significant differences between the two groups. The pain level
      as a whole was low, with the scores ranging from a maximum of 23.4 mm (group 1
      after the first hour) to a minimum of 1.8 min (group 2 after 5, 8 an 10 hours).
      The overall analgesic requirements differed significantly (37.7 vs 17.3 mg
      piritramid, p < .01). There was a difference throughout the whole study period,
      although statistically significant only at the 1., 2. (p < .05), 5. and 6.-8.
      hour (p < .01). This study showed that pain scores were similar after
      laparoscopic upper or open lower abdominal surgery, both requiring adequate
      analgesic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259729
TI  - [Prospective hospital documentation as an instrument of surgical quality
      assurance].
AB  - In this study expenditure and benefits of a differentiated internal hospital
      documentation were analyzed. We particularly wanted to find out whether an
      independent prospective documentation of all postoperative complications has a
      reducing effect on the frequency of these events and therefore can be used as a
      means of control. METHOD: In the time between May 1989 and September 1992 the
      data of 8682 patients of our hospital were documented. Scientific assistants who
      regularly visited every ward registered every course of treatment. All data were
      coded and simultaneously checked. RESULTS: We found the risk of postoperative
      pneumonia (3.6%) especially high in units for vascular surgery and in the
      intensive care unit. Wound infections (5.2%) were mostly seen after
      transplantations and vascular surgery. Specific complications after operations
      showed an accumulation in certain wards. If we look at the progress since 1979 we
      can perceive a significant regression in the rate of wound infections and
      pneumonia and a constant rate of clinical lethality. In elective bowel-resections
      a significant reduction of wound infections and leakages could be recorded.
      Concerning the patient's characteristics we saw apart from a general increase in
      the number of operations a clear increase of endoscopic performances. CONCLUSION:
      Hospital documentation can uncover internal correlations and thus takes part in
      clinical quality assurance. Helpful are evaluations of each specific ward and the
      specific operations. Basis for this is the selection of suitable data and their
      independent evaluation. Measures of external quality assurance have not yet
      solved these problems convincingly.

PMID- 8259730
TI  - [Bassini-Kirschner inguinal hernia surgery--follow-up of 781 primary operations
      in adult men].
AB  - We report on the early and late complications after hernia repair in this
      retrospective study. Over a period of five years, 920 adult men underwent Bassini
      Kirschner repair for inguinal hernia as first operation. There occurred six
      hematomas (0.6%), 11 seromas (1.2%) and 10 wound infections (1.0%). There were no
      deaths. 781 patients were controlled after two to seven years. We found
      recurrence of inguinal hernia in 15 cases (1.9%), chronic inguinal pain in 29
      cases (3.7%), testicular atrophy in two cases (0.2%).

PMID- 8259731
TI  - [Prognostic factors in primary gastric non-Hodgkin's lymphoma--results of uni-
      and multivariate analysis].
AB  - Retrospectively analyzed data of 41 patients with primary gastric non-Hodgkin
      lymphoma which were all treated by gastric resection are presented with regard to
      their histopathologic and clinical findings. 87% of the patients were distributed
      on stage EI and EII (51% high-grade and 49% low-grade lymphoma). R0 resection was
      achieved in 80% of our cases and in 27% of the cases gastric resection was part
      of a multimodal therapy. The median follow up of the living patients was 42
      months, the overall 5-year survival rate 74%. Tumor stage, extent of surgical
      resection, histologic grade, tumor site, R0-resection and tumor size showed a
      significant prognostic influence on survival. The question whether R0 resectable
      cases benefit from an adjuvant therapy must be answered by further randomized
      studies.

PMID- 8259733
TI  - [Specifics of anesthesiology in laparoscopic surgery in infancy].
AB  - No data exist in the literature pertaining to the problems of laparoscopic
      surgery in infants and children. However it is reasonable to assume that minimal
      invasive surgery will find increasing application in these patients in the
      future. The anesthesiological problems met during surgery are representatively
      demonstrated and discussed in the context of a case report. It is shown that in
      infants a reduction of functional residual capacity due to the pneumoperitoneum
      and consequently increased intraabdominal pressure (IAP) cause alveolar collapse,
      increased venous admixture and oxygen desaturation more rapidly than in adults.
      This can be prevented by ventilating with a sufficient level of PEEP. On the
      other hand, the reduction of venous return caused by increased IAP and aggravated
      by the necessarily high PEEP can compromise circulation. Adequate volume
      substitution is essential.

PMID- 8259732
TI  - [Differential diagnosis of ischemia of the lower extremities in young adults].
AB  - Lower-extremity arterial occlusive disease in individuals younger than 50 years
      is rare. We report on 4 young adults with lower limb ischemia, each of them with
      a different cause. According to literature premature atherosclerosis is the most
      common cause and is followed by thromboangiitis obliterans, coagulation
      abnormalities and popliteal artery entrapment syndrome. We suggest a diagnostic
      concept which could help to avoid undue delay.

PMID- 8259734
TI  - [Laparoscopic surgery in the rat: description of a new technique].
AB  - We report a method of laparoscopic surgery in the rat. Our technique is
      illustrated by gastric fundoplication requiring two handed dissection, suturing,
      and knot tying. This animal model for laparoscopic surgery is relatively
      inexpensive, can be extended to other operations, and makes use of an extensively
      studied animal. These factors may facilitate investigation of the physiologic
      effects of minimal access surgery.

PMID- 8259735
TI  - [A comparative study of the content of peripheral and integral proteins in the
      liver microsomal membranes of vertebrates].
AB  - Peripheral and integral protein amounts in liver microsomal membranes of 11
      species of vertebrate animals have been investigated. It was found that the
      peripheral protein content increases in the following sequence: fishes,
      amphibians, reptiles, birds. The content of integral proteins decreases in the
      same sequence. The content of proteins in liver membranes from mammals
      corresponds to that from lower vertebrates.

PMID- 8259736
TI  - [The smooth-muscle adenylate cyclase system of invertebrate and vertebrate
      animals as the target of glucagon action].
AB  - Stimulatory effect, as well as potentiation of the latter by guanine nucleotides,
      of mammalian glucagon on adenylate cyclase system from plain muscles of bivalve,
      gastropod molluscs, holothurians and ascidians have been revealed. The same
      effects were found in tissues of vertebrate animals (human myometrium, aorta and
      liver of rats, stomach and liver of chicks). These data indicate effective
      coupling of all the components of glucagon-sensitive adenylate cyclase system in
      plain muscles of all the investigated animals.

PMID- 8259737
TI  - [The effect of the stimulation of "punishment areas" on the nonspecific
      nociceptive system of the thalamus in an enhanced period of rabbit development].
AB  - Effects of stimulation of areas of the negative reinforcement in hypothalamus and
      adjacent sites on the nociceptive evoked potentials (EP), recorded in the
      thalamic parafascicular complex to electrical skin stimulation of the hind paw in
      30-40 days old rabbits were investigated. The stimulation of areas of the
      negative reinforcement in the anaesthetized animals resulted in the inhibition of
      the EP. Points, yielding the active-defense behaviour in the behavioural
      experiments, inhibited the EPs in the electrophysiological tests at the smaller
      current level (50-80%), than points, yielding the passive-defense behaviour (80
      110%). On the contrary, the recovery period of the EP's parameters after the
      ceasing of the stimulation was shorter, if points were connected with the active
      defense but not the passive-defense behaviour. The data obtained are considered
      in comparison with previous findings obtained in the investigation on the rabbits
      of the same age under the stimulation of areas of the positive reinforcement.

PMID- 8259738
TI  - [The hypothalamic mechanisms of the regulation of neocortical activity in
      representative predators (cats)].
AB  - On complex behavioural model (preference reaction), studies have been made of the
      effect of stimulation of two different hypothalamic nuclei, i.e. ventromedial and
      mammillary ones, on the conditioned reflex activity in cats. It was shown that
      stimulation of the ventromedial nucleus (in contrast to that of the mammillary
      one) exerts more complex differentiated effect on the higher nervous activity.
      Similar effect may be induced by subcutaneous administration of beta-endorphin.
      The data obtained are discussed in relation to the development of two different
      mechanisms of hypothalamic influence on neocortical activity.

PMID- 8259739
TI  - [An ultrastructural analysis of synaptic plasticity during limitation of the
      sensory input].
AB  - Morphometric investigation of ultrastructural changes in synaptic connections
      within visual projection zone in the accessory hyperstriatum and associative part
      of the medial ventral hyperstriatum in chicks, kept in darkness within the first
      day after hatching, revealed reliable decrease in the number and area of active
      synaptic zones together with accumulation of synaptic vesicles in axonal plates.
      Compensatory processes in the investigated structures during normalization of the
      visual function at the second day after hatching in chicks consist of the
      increase in the mean area of contacts without significant increase in the
      relative number of postsynaptic dense bodies, which may indicate intensification
      of synaptic transmission.

PMID- 8259741
TI  - [The interaction of the ideas of scientific schools as the mechanism for the
      formation of gerontology].

PMID- 8259740
TI  - [Structural disruption of the myelin sheaths in the CNS of adult rats with
      hereditary catatonia].
AB  - Ultrastructural studies have been made on the medio-dorsal region of n. caudatus
      and ventromedial part of the corpus callosum in rats with hereditary catatonia.
      In most of the nervous fibres, structural abnormalities were revealed in myelin
      sheaths. Dense myelin is split into several layers at the intraperiod line,
      terminal loops being swollen. Proliferation of oligodendroglia is also observed.
      Most of the mitochondria, both in the glia and nervous fibers, almost completely
      lack cristae. Proportional relationship between two main components of the
      cytoskeleton, i.e. neurofilaments and microtubuli, increases, which may be taken
      as an indication of a compensatory reaction. The observed morphological changes
      may play significant role in disturbances of sleep-wakefulness cycle in rats with
      hereditary catatonia.

PMID- 8259742
TI  - African intermezzo. Home birth, Masai style.

PMID- 8259743
TI  - Oophorectomy in the prevention of ovarian cancer.

PMID- 8259744
TI  - Iron status in Danish women aged 35-65 years. Relation to menstruation and method
      of contraception.
AB  - Iron status was assessed by serum (S-) ferritin and hemoglobin (Hb) in a
      population survey comprising 883 non-gravid Danish women in age cohorts of 35,
      45, 55, and 65 years. Premenopausal women (n = 676) had lower S-ferritin, median
      42 micrograms/l, than postmenopausal women (n = 207), median 80 micrograms/l (p <
      0.0001). Of premenopausal women, 12.1% had S-ferritin < or = 20 micrograms/l
      (i.e. depleted iron stores), and 35.6% S-ferritin of 21-40 micrograms/l (i.e.
      small iron stores). Corresponding figures in postmenopausal women were 0.5% and
      13.2%. Premenopausal blood donors (n = 88) had lower S-ferritin than non-donors
      (p < 0.001). In premenopausal women, S-ferritin levels were strongly dependent on
      the duration of menstrual bleeding (p < 0.0001), which in turn was related to the
      method of contraception. Women (n = 64) using hormonal contraceptives (the pill)
      had menstrual bleeding of shorter duration than those (n = 511) not using pills
      or intrauterine devices (IUD), who in turn had bleeding of shorter duration than
      those (n = 101) using IUD. Median S-ferritin in pill users was 62 micrograms/l,
      in those not using pills or IUD 42 micrograms/l, and in IUD users 36
      micrograms/l. S-ferritin values < 40 micrograms/l (i.e. small and depleted iron
      stores) were seen in 25% of pill users, in 48% of those not using pills or IUD,
      and in 61% of IUD users.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259745
TI  - Phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase
      activity in rat uterus. Cyclic and steroid-induced changes.
AB  - PURPOSE: The activity of phenylethanolamine-N-methyl-transferase (PNMT) and
      catechol-O-methyl-transferase (COMT) was studied in uterine homogenates from
      adult female Wistar rats with normal cycles and that had been ovariectomized,
      adrenalectomized, and steroid-treated. RESULTS: Activities of the two enzymes
      changed significantly during the normal estrus cycle. Both peaked during
      metestrus, with COMT showing a secondary peak of activity at proestrus.
      Progesterone treatment significantly increased and estradiol decreased PNMT
      activity in comparison to untreated controls. Hydrocortisone administration had
      no effect on uterine PNMT activity. COMT activity was not affected significantly
      by any of the steroid treatments. CONCLUSION: The data confirm that uterine
      tissues possess the enzymatic machinery to synthesize epinephrine from
      norepinephrine, and suggest the activity of this pathway may be mediated by
      variations in the sex hormone environment of the uterus.

PMID- 8259746
TI  - Comparison of outcome of labetalol or hydralazine therapy during hypertension in
      pregnancy in very low birth weight infants.
AB  - Ninety-seven women with moderate to severe preeclampsia (PE) were allocated at
      random to labetalol or hydralazine treatment. Of these, 22 women with severe PE
      gave birth to neonates with VLBW (very low birth weight < or = 1500 g). Seven
      were allocated to labetalol treatment (Group A), eight to hydralazine treatment
      (Group B) and seven women received both drugs due to poor blood pressure control
      with a single drug therapy (Group C). No difference in cesarean section rate or
      in the indication for operative delivery could be seen. Gestational age was 29.9
      weeks (25.4-32.5) in Group A, 28.6 weeks (26.6-33.4) in Group B and 27.3 weeks
      (26.7-31.1) in Group C (median and range). Birth weight did not differ between
      groups and 13 of the 22 infants weighed below 1000 g. There was a tendency to
      lower Apgar scores at five minutes in the hydralazine group. Time spent in the
      neonatal intensive care unit did not differ between groups. Five of the 11
      neonates with gestational age (GA) < or = 28 weeks and three of the seven
      neonates in GA 29-30 weeks died. Neither the number of infants requiring
      intermittent positive pressure ventilation or duration of O2- treatment, nor
      number of infants with respiratory distress syndrome differed between groups. We
      did not find any difference in the outcome of the VLBW infants when the
      hypertensive mother had been treated with either hydralazine or labetalol.

PMID- 8259747
TI  - Effect of iron-folate supplementation on serum copper concentration in late
      pregnancy.
AB  - The effect of iron-folate supplementation on maternal serum copper concentration
      in late pregnancy (33 to 35 weeks gestation) was examined. In the 30 women who
      had taken daily iron-folate supplements since the start of the second trimester
      (11 to 15 weeks gestation), the median serum copper concentration was lower than
      that in the 27 women who had taken no supplements (p < 0.005). However, in the
      supplemented women the median values for serum iron concentration and blood
      hemoglobin concentration were higher, and the median value for serum transferrin
      concentration was lower, than the corresponding median values in the
      unsupplemented women (p < 0.001, p < 0.02 and p < 0.001, respectively). Further
      work is needed to determine whether the difference between the median values for
      serum copper concentration is due to a reduction in values in the women who took
      iron-folate, perhaps as a result of an interaction between iron and copper, or is
      due to an increase in values in the unsupplemented women secondary to their
      apparently reduced iron status.

PMID- 8259748
TI  - Ambivalence towards parenthood among pregnant women and their men.
AB  - 369 pregnant women and 345 expectant fathers visiting antenatal clinics were
      examined by a questionnaire concerning attitudes towards pregnancy and
      parenthood. Data were processed by factor analysis and the degree of agreement to
      important factors was estimated. Attitudes were dominated by two conflicting
      views: children mean existential satisfaction and children mean restriction of
      freedom for women as well as for men. There was a tendency to deny the items
      concerning the disadvantages of having children. An important factor in the
      women's as well as in the men's analysis was the importance of own parents as
      models in parenthood. The findings from this unselected population of pregnant
      women and their men are consistent with earlier in-depth interviews. It can be
      concluded that ambivalence should be regarded as a normal constituent of the
      adaptation to pregnancy and parenthood. Experiences of own parents play an
      important role in the transition to parenthood. An important task for the medical
      profession should be to inform about ambivalence as a normal phenomenon as it,
      left unaccepted, may cause unnecessary anxiety and feelings of guilt.

PMID- 8259749
TI  - Management of prelabor rupture of membranes at term. A randomized study.
AB  - OBJECTIVE: To compare the rate of obstetric interventions, length of labor, and
      maternal morbidity in pregnancies with prelabor rupture of membranes at term
      after either early or late induction of labor in both primiparous and pluriparous
      women. DESIGN: Prospective, randomized study. SUBJECTS: 362 women with singleton
      pregnancies, cephalic presentations, gestational age of 36 completed weeks or
      more were allocated at random to induction with oxytocin either 6 hours after
      PROM (n = 62) (early) or 24 hours (n = 62) (late). Those eligible, but not
      participating in the study, totalled 238 women. MAIN OBSTETRIC MEASURES: Time of
      spontaneous labor in the late induction group, length of labor, obstetric
      intervention rate, maternal morbidity, and the degree of histologic
      chorioamnionitis. RESULTS: The length of labor was longer in the late induction
      group than in the early induction group in both primiparous and pluriparous (p <
      0.05). There were no overall differences in the rate of obstetric interventions
      or maternal morbidity, but there were marked differences between primiparous and
      pluriparous women. Increasing time span between the period from rupture of
      membranes to delivery increased the degree of histologic chorioamnionitis.
      CONCLUSION: If a woman wants a short labor, she will benefit from early
      induction. We did not find statistical differences in the rate of obstetric
      intervention or in the maternal morbidity, but there was a tendency towards
      adverse effects of late induction.

PMID- 8259750
TI  - Placental abruption. Maternal risk factors and associated fetal conditions.
AB  - OBJECTIVE: To investigate maternal risk factors and fetal conditions associated
      with abruption. METHODS: Prospective cohort study of 30,681 singleton pregnancies
      at least 28 weeks' gestation. Data collected by patient questionnaire at the
      first prenatal visit and by medical record review. RESULTS: 307 women had
      abruption (1%). After adjustment, important maternal risk factors included age
      (in years; OR 1.03; 95% CL 1.00, 1.06; p = 0.04) and less than 12 years of
      education (OR 1.58; 95% CL 1.10, 2.25; p = 0.01). Each pack of cigarettes smoked
      per day increased the risk by approximately 40% (OR 1.39; 95% CL 1.09, 1.79; p =
      0.009). If abruption occurred, the perinatal mortality rate was substantially
      higher in women who smoked at least one pack per day than in nonsmokers (RR 2.53;
      95% CL 1.14, 5.61; p = 0.02). Abruption was also significantly associated with
      intrauterine growth retardation and fetal malformations. The increased
      malformation rate was due entirely to nearly a five-times increase in congenital
      heart defects (OR 4.63; 95% CL 2.49, 8.55; p = 0.00000014). CONCLUSIONS: Heavier
      smoking increases the risk both of abruption and of perinatal death when
      abruption occurs. If the association between abruption and congenital heart
      defects is confirmed, early evaluation could lead to more prompt treatment of
      these malformations in infants delivered after abruption.

PMID- 8259751
TI  - Cervical conization and preterm delivery/low birth weight. A systematic review of
      the literature.
AB  - OBJECTIVE: Evaluate the effect of cervical conization on preterm birth/low birth
      weight (LBW). DESIGN: A systematic review of the literature using external or
      internal controls. RESULTS: The typical odds ratio for preterm delivery in women
      with prior cervical conization using external controls was 3.23 (95% confidence
      interval 2.29-4.55). Using internal controls the typical odds ratio for LBW was
      2.97 (95% confidence interval 1.09-8.05). Using external controls the typical
      odds ratio for LBW was 2.31 (95% confidence interval 1.33-3.99). CONCLUSION:
      Women with cervical conization are at higher risk for preterm birth than external
      controls, and the surgical intervention as such is a major determining factor.

PMID- 8259752
TI  - Plasma immunoglobulin, total protein and albumin levels during Norplant use by
      Nigerian women.
AB  - OBJECTIVE: To determine the effect of Norplant on plasma immunoglobulins, albumin
      and total proteins. DESIGN: A longitudinal prospective study of Norplant (six
      capsules) subdermal contraceptive implant acceptors. SETTING: Family Planning
      Clinic, University College Hospital, Ibadan, Nigeria. PATIENTS: 36 women
      volunteers aged 18-40 years on Norplant. MAIN OUTCOME MEASURES: Serum
      immunoglobulins, albumin and total protein before, one, three and 12 months after
      Norplant insertion. RESULTS: No statistically significant changes were observed
      in plasma levels of IgA, IgM and total proteins but plasma levels of IgG showed
      statistically significant increases after one, three and 12 months on Norplant.
      CONCLUSION: Norplant does not seem to alter IgM, IgA, albumin and total protein
      levels over a period of 12 months. It, however, induces significant changes in
      IgG levels at one, three and 12 months after insertion. These changes are less
      marked by the end of 12 months.

PMID- 8259753
TI  - A Swedish version of the Women's Health Questionnaire. A measure of
      postmenopausal complaints.
AB  - We wanted to provide details on the psychometric documentation of the Swedish
      version of the Women's Health Questionnaire (WHQ), a patient based measure of
      postmenopausal complaints. The results of two clinical trials in Sweden in which
      the WHQ had been used as one out of several measurement tools were used to
      document the reliability, the validity and the responsiveness to change of the
      WHQ. More than 350 women suffering from postmenopausal complaints were included
      in the two trials. A factor analysis, using the baseline values of all women in
      each study, showed that the Swedish version of the WHQ was very close to the
      English original. The internal consistency reliability was excellent. The
      clinical validity was confirmed by a significant correlation between change in E2
      levels and change in the WHQ during estrogen therapy. A high construct validity
      was established by the agreement between the WHQ and other quality of life
      scales. For use in clinical trials the WHQ was sensitive to treatment-induced
      changes, and added important information to the clinical effect variables.

PMID- 8259754
TI  - Is sexual life influenced by transdermal estrogen therapy? A double blind placebo
      controlled study in postmenopausal women.
AB  - Two hundred and forty-two postmenopausal women between 45 and 65 years of age
      requiring hormone replacement therapy for climacteric symptoms were blindly and
      randomly allocated to treatment either with transdermal estradiol therapy
      (Estraderm 50 micrograms/24h) (E) or placebo (P). The patches were changed twice
      a week and treatment continued for 12 weeks. No progestogen supplement therapy
      was given during the study. No previous hormone replacement therapy had been
      given for the last six months and the women had had their last menstruation more
      than six months ago. As a part of a larger study assessing women's quality of
      life, a Swedish version of 'McCoy's Sex Scale Questionnaire' was administered at
      the start of treatment and after 12 weeks. This questionnaire contains nine items
      regarding different aspects of sexual life. The difference between the scorings
      at the start of treatment and after 12 weeks were calculated for each item and
      the values of the E and the P groups were compared. Items regarding 'satisfaction
      with frequency of sexual activity, sexual fantasies, degree of enjoyment, vaginal
      lubrication and pain during intercourse' were positively influenced in the E
      group compared to the P group. Items not affected were 'frequency of orgasm and
      sexual arousal'. A correlation between improved sexual life and quality of life
      was also found when the results from the McCoy scale were compared with a battery
      of quality of life questionnaires.

PMID- 8259755
TI  - Tests for 'detrusor instability' in women. These mainly measure the urethral
      resistance created by pelvic floor contraction acting against a premature
      activation of the micturition reflex.
AB  - The principal aim of this study was to analyse the simultaneous pressure readings
      derived from bladder and urethra during a handwashing test. A total of 163
      patients with urinary incontinence were studied. It was demonstrated that
      contraction of the pelvic floor stretches the vagina. In many patients, this
      appeared to inhibit the micturition reflex, possibly by supporting the nerve
      endings at bladder neck, thereby inhibiting their premature activation. There was
      also evidence that this stretching activated reflex contraction of the urethra,
      the vagina-urethral (coital) reflex, thereby increasing the urethral resistance.
      On further analysis, it was concluded that urodynamic testing does not detect
      'detrusor instability' per se. It detects the urethra's attempts at closure.

PMID- 8259756
TI  - Osteopenia caused by heparin treatment in pregnancy.
AB  - A case is reported of severe osteopenia caused by heparin treatment of thrombosis
      in the eleventh week of pregnancy followed by heparin prophylaxis (5000 IU three
      times daily) during pregnancy and lactation. The mother complained of back pain
      during the last two weeks of pregnancy. Six weeks post partum, generalized
      osteopenia in the skeleton was diagnosed and a compression fracture of the body
      of the sixth thoracic vertebra. During pregnancy the mother had relatively low
      serum concentrations of 1,25(OH)2D, the active metabolite of vitamin D, and six
      weeks after delivery the serum concentration had fallen to about 50% of the
      lowest reference level. Eight and fourteen weeks after delivery, when heparin
      treatment had been discontinued, the serum concentrations of 1,25(OH)2D were
      within the reference range for non-pregnant adults.

PMID- 8259757
TI  - Endometrioid carcinoma arising from endometriosis of the sigmoid colon during
      estrogenic treatment.
AB  - A case of endometrioid carcinoma arising from endometriosis of the sigmoid colon
      is reported. The patient had been treated with unopposed continuous estrogen
      injection for twenty years after bilateral salpingo-oophorectomy because of
      severe endometriosis. The pathology, pertinent literature and implications of the
      present case are discussed.

PMID- 8259758
TI  - Large solitary luteinized follicle cyst of pregnancy and puerperium.
AB  - A case of large solitary luteinized follicle cyst of pregnancy and the
      puerperium, arising in a 22 year old primipara, three months post partum, is
      presented with clinical and pathological details. This is a rare type of follicle
      cyst and has to be differentiated from a cystic neoplasm.

PMID- 8259759
TI  - Laparoscopic tubal anastomosis: reversal of sterilization.
AB  - A case of laparoscopic reversal of tubal sterilization is reported. The patient
      was a 38 year old woman sterilized by bipolar diathermia two years earlier.
      Refertilization was performed by laparoscopic end to end anastomosis of one tube.
      Postoperatively, the patient had one menstruation and then achieved an
      intrauterine pregnancy. The laparoscopic method of refertilization saves
      expensive hospitalization costs.

PMID- 8259760
TI  - Evaluation of endometrium with transvaginal ultrasound.

PMID- 8259761
TI  - Hypnotherapy and contractures of the hand.
AB  - Contractures of the hand are rather uncommon conversion phenomena. As yet, very
      little is known about treatment. After a brief overview of the literature on the
      various treatment strategies, we describe the treatment of four patients. There
      are indications that a complaint-centered approach, which attempts to influence
      the symptom directly, produces positive results. Hypnotherapeutic techniques were
      used in the four patients described here. Treatment resulted in improvement in
      three of the four.

PMID- 8259762
TI  - Hypnosis and self-hypnosis in the management of nocturnal enuresis: a comparative
      study with imipramine therapy.
AB  - Various therapeutic modalities have been used for treating enuresis due to the
      lack of a single identifiable cause. We carried out a comparative study of
      imipramine and direct hypnotic suggestions with imagery used for the management
      of functional nocturnal enuresis. Enuretic children, ranging in age from 5 to 16
      years, underwent 3 months of therapy with imipramine (N = 25) or hypnosis (N =
      25). After termination of the active treatment, the hypnosis group continued
      practicing self-hypnosis daily during the follow-up period of another 6 months.
      Of the patients treated with imipramine, 76% had a positive response (all dry
      beds); for patients treated with hypnotic strategies, 72% responded positively.
      At the 9-month follow-up, 68% of patients in the hypnosis group maintained a
      positive response, whereas only 24% of the imipramine group did. Hypnosis and
      self-hypnosis strategies were found to be less effective in younger children (5-7
      years old) compared to imipramine treatment. The treatment response was not
      related to the hypnotic responsivity of the patient in either group.

PMID- 8259763
TI  - The use of hypnosis in cocaine addiction.
AB  - An unusual case is presented in which hypnosis was successfully used to overcome
      a $500 (five grams) per day cocaine addiction. The subject was a female in her
      twenties. Six months into her addiction, she acquired a commercial weight-control
      tape that she used successfully to stop smoking cigarettes (mentally substituting
      the word "smoking"), as well as to bring her down from her cocaine high and allow
      her to fall asleep. After approximately 8 months of addiction, she decided to use
      the tape in an attempt to overcome the addiction itself. Over the next 4 months,
      she listened to the tape three times a day, mentally substituting the word
      "coke." At the end of this period, her addiction was broken, and she has been
      drug free for the past 9 years. Her withdrawal and recovery were extraordinary
      because hypnosis was the only intervention, and no support network of any kind
      was available.

PMID- 8259764
TI  - Somatization of dissociated traumatic memories in a case of reflex sympathetic
      dystrophy.
AB  - In this single case report, I examine the treatment of reflex sympathetic
      dystrophy (RSD) with hypnosis and ego-state therapy in a subject with a
      dissociative disorder. RSD is an unusual, debilitating, chronic pain syndrome
      with a usually poor outcome. The subject achieved temporary symptomatic relief
      using hypnosis and auto-hypnotic pain-management techniques. Eventually, she
      achieved permanent relief of RSD symptoms that continued over a two-year follow
      up period. She achieved this permanent relief through a process of
      psychologically integrating physical functions that she experienced as specific
      to several dissociated ego states. This case illustrates the role of metaphor and
      imaginative symbolism in constituting a physical condition. It also illustrates
      how imaginative transformation of the symbolic imagery can induce psychological
      and physical change.

PMID- 8259766
TI  - Hypnosis and music.

PMID- 8259765
TI  - Hypnobehavioral therapy to reduce gag and emesis with a 10-year-old pill
      swallower.
AB  - A 10-year-old child experienced severe nausea and psychogenic vomiting that
      resulted in refusal to take oral medication in pill form. The youngster was
      treated with hypnobehavioral therapy consisting of mental imagery, relaxation,
      direct suggestion, adaptive self-talk, self-monitoring, and self-reinforcement.
      The child's parents were instructed to reinforce approximations of successful
      pill swallowing while withdrawing attention for avoidance, whining, gagging, and
      vomiting. A one-year follow-up revealed successful pill swallowing without
      significant distress.

PMID- 8259767
TI  - The use of music as a hypnotic suggestion.
AB  - We have known of the interaction between music and mood for many years. In this
      paper, I present a series of case vignettes to illustrate a method using music to
      affect mood. In hypnosis, I suggested that subjects imagine hearing a piece of
      music appropriate to a desired emotion, rather like a sound track for a movie. I
      suggested that the patients vividly recall this music and the accompanying
      feelings outside of trance when it would be desirable to help them to change
      their behavior by influencing their emotional state. In this way, music can be
      used to shape emotion.

PMID- 8259768
TI  - Cross validation of the Hypnotic Induction Profile factor structure: simultaneous
      confirmatory factor analysis of two published samples.
AB  - This study cross-validated factor structure and psychometric characteristics of
      the Hypnotic Induction Profile (HIP). Earlier studies identified two constructs
      of the HIP, but their methodology did not allow empirical confirmation of the
      number of factors. I have used a new methodology, confirmatory factor analysis,
      and submitted the data from the previous studies to a simultaneous, multisample,
      factor analysis. The results showed that the HIP indeed consists of two factors.
      Although the HIP two-factor model is statistically adequate, 7 of the 10 scales
      have very low item reliability. Issues of measurement error and clinical
      implications of the study are also discussed in relation to the current findings.

PMID- 8259769
TI  - Chronic insomnia: outcome of hypnotherapeutic intervention in six cases.
AB  - Chronic dyssomnia is highly prevalent and has multiple etiologies. Hypnotherapy
      has been reported as beneficial for insomnia, but the description of the subject
      populations has been limited. A group of patients was evaluated at a sleep
      disorders center for a dyssomnia that occurred on at least 3 nights per week for
      6 months or more. Six patients accepted hypnotherapy for their persistent
      psychophysiological insomnia and other sleep disorder diagnoses. Three patients
      responded to two sessions of structured hypnotherapy. The three responders
      remained improved at 16-month follow-up. Factors that seemed to contribute to
      long-term response in this small group of patients included a report of sleeping
      at least half of the time while in bed, increased hypnotic susceptibility, no
      history of major depression, and a lack of secondary gain.

PMID- 8259770
TI  - Unifying internal medicine: criteria for survival.

PMID- 8259771
TI  - Cyclic etidronate: has the rose lost its bloom?

PMID- 8259772
TI  - Four-year study of intermittent cyclic etidronate treatment of postmenopausal
      osteoporosis: three years of blinded therapy followed by one year of open
      therapy.
AB  - PURPOSE: To determine the effect of long-term intermittent cyclic etidronate
      treatment on spinal bone density and vertebral fracture rates. PATIENTS AND
      METHODS: Postmenopausal osteoporotic women (n = 423) were randomized initially
      into a 2-year, double-blind, multicenter study; it was extended to a third year
      of blinded treatment followed by open-label treatment: 357 patients continued
      treatment in Year 3 (305 receiving blinded therapy and 52 receiving calcium
      supplementation) and 277 in Year 4. During Years 1 through 3, patients received
      double-blind treatment with phosphate (1.0 g) or placebo twice daily for 3 days,
      etidronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) daily for
      the remainder of each 91-day treatment cycle. During Year 4, open-label
      intermittent cyclic etidronate therapy (without preceding phosphate) was
      administered to all patients. Spinal bone density and vertebral fracture rates
      were the main outcome measures. RESULTS: During Year 3, etidronate therapy
      maintained the significant increases in spinal bone mineral density of the first
      2 years. Over the 3-year period, proximal femur bone density increased in
      etidronate-treated patients. Etidronate therapy for 3 years significantly
      decreased the vertebral fracture rate in patients at higher risk for fracture
      (low spinal bone density and three or more vertebral fractures at study entry),
      as compared with nonetidronate treatment (228 versus 412 fractures per 1,000
      patient-years, respectively; p < 0.05). After 1 year of open-label treatment,
      patients previously treated with etidronate maintained bone mass, and vertebral
      fracture rates in all groups were lower than in any other study period. There
      were no apparent serious adverse effects. CONCLUSIONS: Three years of
      intermittent cyclic etidronate therapy produced significant increases in spinal
      and hip bone density, with a significant reduction in vertebral fracture rates in
      patients at higher fracture risk. Maintenance of bone mass and low fracture rate
      were observed when etidronate was continued for an additional year.

PMID- 8259773
TI  - Bone mineral status of women with Marfan syndrome.
AB  - PURPOSE: With effective surgical correction of vascular abnormalities, skeletal
      health is an important issue for patients with Marfan syndrome. Osteopenia has
      been radiographically described, yet no systematic evaluation of bone status has
      been published. The purpose of this study was to determine the bone mineral
      density (BMD, g/cm2) in women with Marfan syndrome. PATIENTS AND METHODS:
      Seventeen women, 37.2 +/- 7.3 years old, with Marfan syndrome were studied. Dual
      energy x-ray absorptiometry (DXA) was used to measure BMD at the lumbar spine (L2
      L4), proximal femur, and total body in all subjects. Scoliosis scores were
      assigned from 0 (no curvature) to 3 (severe curvature). RESULTS: Highly
      significant deficits in BMD were observed at the proximal femur (p = 0.0001) as
      well as of the whole body (p < 0.05). Femoral neck BMD Z-score (mean +/- SD) = 
      1.36 +/- 0.94, trochanter Z = -1.07 +/- 0.80, and intertrochanter Z = -1.44 +/-
      0.71; whole-body BMD Z-score = -0.30 +/- 0.16. BMD at L2-L4, however, did not
      differ from age-predicted values, Z = -0.48 +/- 1.16. There was no significant
      association between BMD and scoliosis, nor between BMD and fracture history. To
      correct for bone size, the bone mineral apparent density (BMAD, g/cm3) was
      calculated. The femoral neck BMAD values (mean +/- SD) were significantly lower
      than predicted (0.125 +/- 0.02 versus 0.147 +/- 0.001 g/cm3, p < 0.001). All
      subjects had normal menarche, and 15 reported regular menses. There was no
      history of nontraumatic fracture. CONCLUSIONS: Women with Marfan syndrome have
      bone deficits at the proximal femur as well as of the whole body. This deficit is
      not related to scoliosis and persists when corrected for bone size. Women with
      Marfan syndrome may be at increased risk for proximal femoral fracture.

PMID- 8259774
TI  - Immunogenicity of two recombinant hepatitis B vaccines in older individuals.
AB  - PURPOSE: Currently available hepatitis B vaccines are recombinant, yeast-derived
      preparations given in 10-micrograms or 20-micrograms doses. The optimum dose
      remains controversial. We sought to assess the relative immunogenicity of two
      hepatitis B vaccines, given in different doses, in older individuals. PATIENTS
      AND METHODS: In a multicenter, double-blind, randomized clinical trial, a total
      of 460 healthy subjects between 39 and 70 years of age were screened and
      immunized with either Engerix-B 20 micrograms or Recombivax HB 10 micrograms in
      standard, intramuscular, 3-dose regimens. Of these, 397 subjects were eligible to
      continue vaccination. Immunogenicity was measured by determination of antibody to
      hepatitis B surface antigen (anti-HBs). Seroconversion and seroprotection rates,
      and geometric mean titers of anti-HBs were calculated at 1, 3, 6, and 8 months
      after the initial dose of vaccine. RESULTS: Seroprotection rates for subjects
      receiving the 20-micrograms dose of vaccine were slightly, but not significantly,
      greater than for subjects receiving the 10-micrograms dose, at each time point.
      However, at 3 months, males receiving the higher dose had significantly higher
      seroprotection rates than males receiving the lower dose: 63% versus 37% (p <
      0.001). At 8 months, geometric mean titers for the group receiving Engerix-B 20
      micrograms were significantly greater than that for the group receiving
      Recombivax HB 10 micrograms: 840 mIU/mL versus 340 mIU/mL (p = 0.001).
      CONCLUSIONS: Immunization with the 20-micrograms dose of recombinant hepatitis B
      virus vaccine appeared to result in more rapid development of seroprotective anti
      HBs titers in older men and in higher titers of anti-HBs at the completion of
      vaccination when compared to the 10-micrograms dose. The latter data suggest that
      the 20-micrograms dose may result in a longer duration of seroprotective anti-HBs
      titers.

PMID- 8259775
TI  - Immunogenicity of the 23-valent pneumococcal polysaccharide vaccine in Alaska
      Native chronic alcoholics compared with nonalcoholic Native and non-Native
      controls.
AB  - PURPOSE: This study was designed to evaluate the immunogenicity of the 23-valent
      pneumococcal polysaccharide vaccine in Alaska Native chronic alcoholics and
      compare these responses with those in age- and sex-matched nonalcoholic, Native
      and non-Native control subjects. PATIENTS AND METHODS: Native alcoholic patients
      were recruited from the inpatient medical service and outpatient clinics. Healthy
      age- and sex-matched Alaska Native and non-Native nonalcoholics were recruited
      from hospital employees. At the initial visit, a standardized questionnaire, the
      Alcohol Dependency Scale, was administered to all participants. Participants were
      examined for liver diseases; blood was drawn for liver function tests and
      prevaccination pneumococcal antibody levels. Charts of all Native participants
      were reviewed for alcohol-related diseases. Participants received one dose of the
      23-valent pneumococcal vaccine at the time of the initial visit and returned 20
      to 55 days after immunization for liver function tests and pneumococcal antibody
      level measurement. Serotype-specific pneumococcal antibody levels were measured
      by radioimmunoassay. Logistic regression analysis was used to examine the
      proportion of persons whose serotype-specific antibody level doubled following
      vaccination. A model including adjustments for age, sex, and initial antibody
      level was used to examine the effect of alcohol status and ethnicity on response
      to the vaccine. Eighty-five persons completed the study. Of these, 41 were
      chronic alcoholics and 44 were nonalcoholic. Of these, 21 were Alaska Natives and
      23 were non-Natives. RESULTS: Before vaccination, the geometric mean titers
      (GMTs) were similar in all 3 groups but were slightly higher in Native alcoholic
      participants for 11 of 12 serotypes tested. For 11 or more serotypes tested, 46%
      of alcoholics and 27% of nonalcoholics had total antibody levels at or above 500
      nanograms of antibody nitrogen per milliliter (p = 0.11). After vaccination, the
      GMTs were higher in nonalcoholic than in alcoholic participants for serotypes 3,
      7F, and 19F (p < 0.05). When Natives and non-Natives were compared, non-Natives
      had higher antibody levels than Native participants for 10 of 12 serotypes. After
      vaccination, 83% of alcoholics and 91% of nonalcoholics had pneumococcal antibody
      levels of more than 500 nanograms of antibody nitrogen per milliliter for at
      least 11 serotypes. When responses consisting of a twofold or greater increase in
      antibody level were compared, a greater proportion of nonalcoholics than
      alcoholics responded to serotypes 3, 4, 7F, 8, and 19F. This difference was
      significant for types 3 and 19F only (p < 0.05). In alcoholics there was a direct
      correlation between pneumococcal antibody level and age both before and after
      vaccination. This was significant before vaccination for serotypes 4, 6B, 18C,
      and 23F, and after vaccination for these types and for types 1 and 19F. In
      nonalcoholics there was a correlation between age and antibody response,
      following vaccination, for serotype 9N and 18C. Alcoholic males had antibody
      levels higher than that in females for most serotypes, but significantly so only
      for serotype 12F before vaccination, and for type 14 after vaccination. There
      were no sex differences seen among nonalcoholics, and no differences in response
      to vaccine could be detected in patients with or without liver dysfunction.
      CONCLUSION: In this study of Alaska Natives with chronic alcoholism, Native and
      non-Native participants responded adequately to immunization with the 23-valent
      pneumococcal vaccine, although significant differences in some serotypes were
      evident.

PMID- 8259776
TI  - Antibodies to the constitutive 73-kd heat shock protein: a new marker of mixed
      connective tissue disease?
AB  - PURPOSE, PATIENTS, AND METHODS: This report documents the finding of an elevated
      titer of IgG reacting with the constitutive bovine 73-kd heat shock protein (HSP)
      in the serum of patients with rheumatoid arthritis, scleroderma, and mixed
      connective tissue disease (MCTD). RESULTS AND CONCLUSIONS: Further
      characterization of antibodies from patients with MCTD showed that the antibodies
      also recognize the human constitutive 73-kd HSP, but not the inducible 72-kd
      isoform. Very high levels of antibodies appeared to be specific for MCTD; the
      differences between levels in patients with MCTD and those in healthy subjects
      (blood donors) were highly significant (p < 10(-8)), with no values in this group
      of patients overlapping with those in the controls. This parameter might
      therefore represent a new diagnostic marker for this disease.

PMID- 8259777
TI  - Quantitative culture of bronchoalveolar lavage fluid for the diagnosis of
      bacterial pneumonia.
AB  - PURPOSE: A prospective study to determine the usefulness of quantitative
      bacterial cultures of fluid obtained via fiberoptic bronchoscopy and
      bronchoalveolar lavage as an aid in the diagnosis of bacterial pneumonia.
      PATIENTS AND METHODS: All patients undergoing fiberoptic bronchoscopy with
      bronchoalveolar lavage during a 6 1/2-month period. Presence of pneumonia was
      determined using clinical, radiographic, laboratory, and histologic data.
      Quantitative bacterial cultures of bronchoalveolar lavage fluid were determined
      using a 1-microL culture loop. RESULTS: Quantitative bacterial cultures of
      bronchoalveolar lavage (BAL) fluid were sensitive and specific predictors of
      bacterial pneumonia. Using 10(3) colony-forming units (cfu)/mL as the threshold
      value for a positive culture, we determined the sensitivity and specificity to be
      90% and 97%, respectively. The data were also analyzed for the subgroups of
      patients who were intubated or were receiving antibiotics. The sensitivity and
      specificity were 78% and 96% for the group of patients receiving antibiotics and
      100% and 82% for the group of patients intubated for more than 24 hours at the
      time of BAL. Values for the area under the receiver operating characteristic
      curve for the 3 groups were 0.94, 0.88, and 0.96, respectively. CONCLUSIONS:
      Quantitative bacterial cultures of BAL fluid are sensitive and specific in the
      diagnosis of bacterial pneumonia. The use of antibiotics at the time of BAL
      reduces the sensitivity of the test, and prolonged intubation reduces the
      specificity of the test.

PMID- 8259778
TI  - Prognostic value of dipyridamole echocardiography early after uncomplicated
      myocardial infarction: a large-scale, multicenter trial. The EPIC Study Group.
AB  - PURPOSE: To determine the prognostic capability of the dipyridamole
      echocardiography test (DET) early after an acute myocardial infarction. PATIENTS
      AND METHODS: On the basis of 11 different echocardiographic laboratories, all
      with established experience in stress echocardiography and fulfilling quality
      control requirements for stress echocardiographic readings, 925 patients were
      evaluated after a mean of 10 days from an acute myocardial infarction and
      followed up for a mean of 14 months. RESULTS: During the follow-up, there were 34
      deaths and 37 nonfatal myocardial infarctions; 104 patients developed class III
      or IV angina and 149 had coronary revascularization procedures (bypass or
      angioplasty). Considering all spontaneous events (angina, reinfarction, and
      death), the most important univariate predictor was the presence of an inducible
      wall motion abnormality after dipyridamole administration (chi 2 = 45.8). With a
      Cox analysis, echocardiographic positivity, age, and male gender were found to
      have an independent and additive value. Considering survival (and, therefore,
      death as the only event), age was the most meaningful parameter, followed by the
      wall motion score index during dipyridamole administration (chi 2 = 12.1). Among
      other parameters, the resting wall motion score index was a significant predictor
      of death. In a multivariate analysis, the prognostic contributions of age
      (relative risk estimate = 1.08) and wall motion score index during dipyridamole
      administration (relative risk estimate = 4.1) were independent and additive. In
      particular, considering death only, the event rate was 2% in patients with
      negative DET results, 4% in patients with positive high-dose DET results, and 7%
      in patients with positive low-dose DET results. CONCLUSIONS: DET is feasible and
      safe early after uncomplicated myocardial infarction and allows effective risk
      stratification on the basis of the presence, severity, extent, and timing of the
      induced dyssynergy.

PMID- 8259780
TI  - Infection with the human immunodeficiency virus in prisoners: meeting the health
      care challenge.
AB  - The magnitude and the scope of health care problems posed by human prison inmates
      seropositive for the human immunodeficiency virus (HIV) are enormous. Prisoners
      represent a substantial proportion of HIV-infected individuals in North America.
      A high proportion of prisoners are intravenous drug users who often have not
      received appropriate health care or HIV-directed services prior to incarceration.
      Health care of HIV-seropositive prisoners and follow-up medical care after prison
      release has often been less than optimal. Among inmates at the prison facility in
      Rhode Island, 4% of the men and 12% of the women are HIV seropositive. The Brown
      University medical community, in conjunction with the Rhode Island Department of
      Health and Corrections, has developed an effective program for the health care of
      such prisoners, both during incarceration and after release from prison. Academic
      medical centers are uniquely poised to assume the leading role in meeting this
      obligation. We believe that this general approach, with region-specific
      modifications, may be effectively applied in many correctional institutions in
      North America.

PMID- 8259779
TI  - How well is the Patient Self-Determination Act working?: an early assessment.
AB  - OBJECTIVES: To assess the association between implementation of the Patient Self
      Determination Act (PSDA) and (1) the use of formal, written advance directives,
      (2) the use of informal advance care arrangements, and (3) discussions between
      patients and their physicians and proxies an advance care planning and end-of
      life treatment preferences. DESIGN: A time-sequence study in which patients
      discharged from acute care hospitals 1 month before the implementation of the
      PSDA and 5 months after implementation of the PSDA were interviewed. SETTING: Two
      medical school-affiliated, major teaching hospitals with more than 500 beds and 3
      nonteaching community hospitals with fewer than 400 beds in eastern
      Massachusetts. PATIENTS: A total of 579 adult patients were interviewed: 258
      patients discharged before the implementation of the PSDA (pre-PSDA) and 321
      patients discharged 5 months after implementation of the PSDA (post-PSDA).
      MEASUREMENTS: Patients were asked about their formal, written or informal advance
      care planning arrangements, about the frequency of inquiries and information
      provided on advance care planning by the hospitals, and about their discussions
      of advance care planning and end-of-life treatment preferences with physicians
      and their proxies. RESULTS: In the pre-PSDA cohort, 60.9% of the patients had
      some kind of advance care planning, whereas in the post-PSDA cohort, 72.6% did (p
      = 0.01). However, there was not a significant increase in the proportion of
      patients who had advance care planning "in a written document" (19.8% of the pre
      PSDA cohort compared with 25.5% of the post-PSDA cohort, p = 0.11). The increase
      in written advance care planning was concentrated in the community, nonteaching
      hospitals (10.7% pre-PSDA versus 23.7% post-PSDA). Overall, 41.4% of patients
      recalled inquiries or information about advance care planning during their
      hospitalization. Implementation of the PSDA was not associated with a significant
      change in the proportion of patients who discussed advance care planning or end
      of-life issues with their physicians (13.6% pre-PSDA versus 17.1% post-PSDA, p =
      0.25). However, there was an increase in the proportion of patients with poorer
      health who spoke with their physicians (15.4% pre-PSDA versus 24.8% post-PSDA).
      Implementation of the PSDA was associated with an increase in the proportion of
      patients who had general discussions with proxies about end-of-life issues (61.8%
      pre-PSDA versus 73.0% post-PSDA, p = 0.024). However, 33.6% of pre-PSDA and 33.2%
      of post-PSDA patients had detailed discussions with their proxy about specific
      interventions such as mechanical ventilation or artificial nutrition. Patients
      with formal proxies had detailed discussions significantly more frequently than
      other patients (50.0% versus 26.8%, p < 0.0001). CONCLUSIONS: The PSDA was
      associated with significant effects on general advance care planning issues,
      increasing the proportion of patients who had (1) some kind of advance care
      arrangements and (2) general discussions of end-of-life issues with their
      proxies. However, the PSDA did not appear associated with significant increases
      (1) in the use of formal, written advance care documents, (2) in the frequency of
      discussions between patients and their physicians on advance care documents or
      end-of-life issues, or (3) in the frequency of discussions about specific
      treatment preferences between patients and their proxies.

PMID- 8259781
TI  - Prolactin and immunomodulation.
AB  - PURPOSE: To review the recent exploration of the role of prolactin in immune
      function. MATERIALS AND METHODS: Studies published that were identified through a
      MEDLINE search as well as through the bibliographies of those articles
      enumerated. RESULTS: Both humoral and cell-mediated immunity are compromised in
      hypophysectomized rats. The reintroduction of prolactin to these animals restores
      their immune function. Prolactin receptors have been identified on the membranes
      of white blood cells; furthermore, lymphocytes have been shown to secrete
      prolactin. Cyclosporin A directly competes with prolactin for binding to these
      receptors. This may be one mechanism of the immunosuppressive action of
      cyclosporin A. In addition to diminished levels, prolactin excess may also result
      in immunocompromise. This has been demonstrated in lactating female and prolactin
      treated male rats, as well as hyperprolactinemic humans. Finally, prolactin
      abnormalities have been described in a number of immunologic disorders, including
      systemic lupus erythematosus, adjuvant arthritis, experimental allergic
      encephalomyelitis, and autoimmune uveitis and thyroid disease. Dopaminergic
      agents that suppress serum prolactin are now being used in clinical trials to
      treat a number of autoimmune diseases and to prevent rejection in organ
      transplant recipients. CONCLUSION: At physiologic levels, prolactin is trophic
      for lymphocytes. Either too much, or too little, prolactin may be
      immunosuppressive. Lymphocytes produce a prolactin-like substance. Prolactin may
      play a role in a number of autoimmune processes.

PMID- 8259782
TI  - Differentiating systolic from diastolic heart failure: pathophysiologic and
      therapeutic considerations.
AB  - PURPOSE: To compare and contrast the pathophysiology and therapy of heart failure
      with normal and abnormal systolic ventricular function. METHODS: Review of basic
      pathophysiologic mechanisms, clinical data, and therapeutic trials. CONCLUSIONS:
      The clinical features of heart failure may be similar regardless of whether
      ventricular function is normal or abnormal. However, the pathophysiologic
      mechanisms leading to heart failure with normal ventricular function differ
      considerably from those producing heart failure with abnormal systolic function.
      The key problems in heart failure with abnormal systolic function involve
      impaired contractility, neuroendocrine activation, increased intracardiac volume
      and pressure, and enhanced sensitivity to change in afterload. With normal
      systolic function, the key problem is an abnormal diastolic pressure/volume
      relationship, which may be due to a variety of active and passive processes
      affecting diastole. Assessing left ventricular systolic function is crucial
      before initiating therapy in a patient with heart failure, since treatment for
      systolic dysfunction may be ineffective or even counterproductive if symptoms are
      due to abnormal diastolic properties with preserved systolic function.

PMID- 8259783
TI  - Legislating care for her mother.

PMID- 8259784
TI  - Diffuse osteosclerosis in intravenous drug abusers.

PMID- 8259785
TI  - Heparin-induced skin necrosis.

PMID- 8259786
TI  - Neurosyphilis in HIV-infected patients.

PMID- 8259787
TI  - From Lillian Wald to Hillary Rodham Clinton: what will happen to public health
      nursing?

PMID- 8259788
TI  - Virus transmission in health care settings: precautions, epidemiologic
      experience, and common sense.

PMID- 8259789
TI  - New lessons from China: equity and economics in rural health care.

PMID- 8259790
TI  - Salmonella enteritidis infections in France and the United States: causes vs
      causal models.

PMID- 8259791
TI  - Hormone replacement therapy: the need for reconsideration.
AB  - Millions of menopausal women are taking hormone supplements. Observational
      studies suggest that unopposed estrogens reduce the risk of cardiovascular
      disease and fractures and increase the risk of endometrial cancer and, possibly,
      breast cancer. In the absence of information from randomized trials, how much of
      the apparent beneficial effect on heart disease is due to the tendency of
      healthier women to use these drugs is unknown. The effect on the cardiovascular
      system of estrogen taken with a progestin is unknown, and this regimen may
      increase the risk of breast cancer. An approach to health and illness that
      focuses on a single cause or preventive and on single organ systems is severely
      limited. Alternative ways to improve cardiovascular and skeletal health that do
      not increase the risk of cancer are available. A reconsideration of the
      appropriate use of hormone supplements is needed.

PMID- 8259792
TI  - Public health nursing--the opportunity of a century.

PMID- 8259793
TI  - Commentary: going to the people--public health nursing today and tomorrow.

PMID- 8259794
TI  - An outbreak of hepatitis A among health care workers: risk factors for
      transmission.
AB  - OBJECTIVES: The purpose of this study was to investigate a nosocomial outbreak of
      hepatitis A that occurred in the burn treatment center of a referral hospital.
      METHODS: Retrospective cohort and case-control studies were performed to
      determine acquisition rates and risk factors for transmission. Adjusted infection
      rates were calculated by week of exposure. A case-control study was conducted to
      determine potential mechanisms for nosocomial acquisition. Recently infected
      health care workers were defined as case patients; exposed, serosusceptible
      health care workers without infection served as controls. RESULTS: The outbreak
      of hepatitis A affected 11 health care workers and 1 other burn patient (1
      secondary patient case). All 11 health care workers became ill after the
      admission of a man and his 8-month-old son who developed hepatitis A while in the
      hospital. The cumulative incidence risk ratio was elevated for health care
      workers caring for either the infant or the father during the same week of
      exposure. The case-control study implicated the behavior of eating on the
      hospital ward as the single most important risk factor for infection. CONCLUSION:
      Inadequate hand-washing and subsequent oral contamination appear responsible for
      the outbreak. Hospitals may witness other institutional outbreaks if health care
      workers regularly eat on the wards.

PMID- 8259795
TI  - Hepatitis B control in China: knowledge and practices among village doctors.
AB  - OBJECTIVES: To guide development of a hepatitis B control program in China, we
      investigated village doctors' sterilization practices, injection use, vaccination
      levels, and knowledge and counseling skills. METHODS: The head doctor from each
      village health station in a rural county (n = 260) completed a self-administered
      questionnaire. RESULTS: Of the respondents, 94.2% reported adequate sterilization
      of needles; however, inadequate sterilization of syringes and acupuncture needles
      was common. Injections were found to be frequent and profitable. Of head doctors,
      16.2% reported that most infants in their villages are vaccinated against
      hepatitis B. There was very high knowledge of modes of hepatitis B transmission,
      but it was not used to formulate advice for a hypothetical carrier. Knowledge of
      the consequences, prevalence, and use of condoms to prevent sexual transmission
      was lower. CONCLUSIONS: The sterilization of acupuncture needles, reuse of
      syringes, and frequent injections are practices that may transmit the hepatitis B
      virus. Research into issues of vaccine acceptance is needed to expand
      immunization. A review of treatment practices and better training in counseling
      for village doctors is suggested.

PMID- 8259796
TI  - Patient-to-patient transmission of hepatitis B in a dermatology practice.
AB  - OBJECTIVE: The purpose of the study was to investigate infection with hepatitis B
      virus (HBV) and human immunodeficiency virus (HIV) among patients in a
      dermatology practice. METHODS: Historical cohort, matched case-control, and cross
      sectional survey methods were used. RESULTS: The age-specific incidence of
      reported HBV infection in the practice from 1985 through 1991 was more than 12
      times the expected rate. The dermatologist was not an HBV carrier. He practiced
      neither universal precautions nor sterile surgical technique. Seroprevalence of
      markers for HBV infection was highest (36.8%) among patients who had had surgery
      on the same day that HBV was apparently acquired by an index case; seroprevalence
      was near the expected background level for patients not exposed to index cases.
      Of HBV-infected patients with known dates of onset, 72% had had surgery during
      their incubation periods. All of 30 HBV antigen specimens tested were of the same
      subtype. None of the patients tested, including 74 patients exposed to surgery on
      the same day as a patient with acquired immunodeficiency syndrome, had evidence
      of HIV infection. CONCLUSIONS: HBV, but not HIV, was transmitted from patient to
      patient by the dermatologist's failure to apply either universal precautions or
      sterile surgical technique.

PMID- 8259797
TI  - Salmonella enteritidis infections in France and the United States:
      characterization by a deterministic model.
AB  - OBJECTIVES: Epidemiological surveillance can be used to identify problems,
      suggest hypotheses, and assess the effectiveness of preventive actions. These
      objectives are pursued in the analysis of the dynamic evolution of Salmonella
      enteritidis infections. In this analysis, development of the epidemic in France
      and the United States is compared. METHODS: This analysis is based on the
      formulation of a simple deterministic compartmental model, in which human contact
      with contaminated food is expressed in terms of a baseline transmission rate.
      RESULTS: In France, the baseline transmission rate, stable up until 1986, is
      multiplied by 2.3 in 1987 and by 4.1 in 1988. There is no evidence of a slowdown
      of the linear rate of increase. In the Middle Atlantic region of the United
      States, the linear increase of the epidemic is similar to that observed in
      France. From 1990 a potential effect of the preventive measures is observed.
      CONCLUSIONS: The pattern of increase of the baseline transmission rate is similar
      in France and in the Middle Atlantic region of the United States. However,
      preventive measures, used in both areas, appeared more effective in the United
      States.

PMID- 8259798
TI  - The health effects of swimming at Sydney beaches. The Sydney Beach Users Study
      Advisory Group.
AB  - OBJECTIVES: The purpose of the study was to determine the health risks of
      swimming at ocean beaches in Sydney, Australia. METHODS: From people attending 12
      Sydney beaches in the period from December 5, 1989 to February 26, 1990, we
      recruited a cohort of 8413 adults who agreed to participate in this study. Of
      these, 4424 were excluded either because they had been swimming in the previous 5
      days or because they reported a current illness. Of the remainder, 2839
      successfully completed a follow-up telephone interview conducted within 10 days
      after recruitment. We recorded reported respiratory, gastrointestinal, eye, and
      ear symptoms and fever that occurred within the 10 days between initial interview
      on the beach and the follow-up interview. RESULTS: A total of 683 participants
      (24.0%) reported experiencing symptoms in the 10 days following initial
      interview. Of these, 435 (63.7%) reported respiratory symptoms. Swimmers were
      almost twice as likely as nonswimmers to report symptoms. There was a linear
      relationship between water pollution and all reported symptoms with the exception
      of gastrointestinal complaints. CONCLUSIONS: Swimmers at Sydney ocean beaches are
      more likely to report respiratory, ear, and eye symptoms than beachgoers who do
      not swim. The incidence of these symptoms increases slightly with increasing
      levels of pollution.

PMID- 8259799
TI  - Cat scratch disease in the United States: an analysis of three national
      databases.
AB  - OBJECTIVES: Current knowledge of the epidemiology of cat scratch disease is based
      primarily on information from case series. We used three national databases to
      obtain more representative data to determine the incidence and demographics of
      cat scratch disease. METHODS: Records coded with the diagnosis of cat scratch
      disease from two hospital discharge databases and an ambulatory care database
      were analyzed. Costs of diagnostic tests and hospitalization were obtained from a
      sample of providers and published data. RESULTS: The incidence of patients
      discharged from hospitals with a diagnosis of cat scratch disease was between
      0.77 and 0.86 per 100,000 population per year. Fifty-five percent of the case
      patients were 18 years of age or younger. Males accounted for 60% of cases.
      Incidence varied by season; approximately 60% of case patients were discharged in
      the months September through January. The estimated incidence of disease in
      ambulatory patients was 9.3 per 100,000 population per year. On the basis of
      these rates, we estimated the annual health care cost of the disease to be more
      than $12 million. CONCLUSIONS: The rates and seasonality of cat scratch disease
      found in this study were consistent with previous reports. Adults represented a
      higher percentage of the total than reported in previous case series, suggesting
      that the disease may affect more adults than previously recognized.

PMID- 8259800
TI  - Estimates of the US health impact of influenza.
AB  - OBJECTIVES: Data from the Tecumseh Community Health Study were used to estimate
      excess morbidity owing to influenza, and results were compared with estimates
      made previously using different methodology for an Institute of Medicine report.
      METHODS: Study participants from Tecumseh, Michigan, were classified as infected
      or noninfected based on laboratory results. The excess numbers of respiratory
      illnesses, respiratory illness days, and bed and restricted activity days
      experienced by the infected compared with the noninfected were estimated.
      RESULTS: The number of excess influenza-related respiratory illnesses was lower
      than that estimated in the Institute of Medicine report, in which all illnesses
      of certain characteristics occurring during an influenza season were attributed
      to influenza. It is now estimated that the US population under 20 years of age
      experiences a yearly average of 13.8 to 16.0 million influenza-related excess
      respiratory illnesses; for older individuals, the yearly estimate is 4.1 to 4.4
      million excess illnesses. CONCLUSIONS: For public health purposes, estimates of
      excess morbidity as well as of total morbidity associated with influenza should
      be used in setting health priorities.

PMID- 8259801
TI  - The risk of measles, mumps, and varicella among young adults: a serosurvey of US
      Navy and Marine Corps recruits.
AB  - OBJECTIVES: To assess the risk of epidemic transmission and to guide immunization
      policy, the seroprevalence of antibody to measles, mumps, and varicella was
      determined in a group of young adults. METHODS: A cross-sectional study of 1533
      US Navy and Marine Corps recruits was conducted in June 1989. Antibody status was
      determined with commercially available enzyme-linked immunosorbent assays.
      RESULTS: Direct sex and race adjustment to the 15- to 29-year-old US population
      resulted in seronegativity rates of 17.8% for measles, 12.3% for mumps, and 6.7%
      for varicella. Measles and mumps seronegativity rates were higher among Whites
      whereas varicella seronegativity was higher among non-Whites. Recruits enlisting
      from outside the 50 US states, especially those from island territories, were
      more likely to lack varicella antibody. The sensitivity of a positive history of
      vaccination or disease in predicting antibody status was less than 90% for all
      diseases. CONCLUSIONS: These results suggest a continued potential for epidemics,
      especially of measles, and the need for mandatory immunization policies.
      Immigrants to the United States, especially those from island territories, may be
      a high-risk group that could benefit from varicella vaccination.

PMID- 8259802
TI  - Multiethnic variations in the pregnancy outcomes of military dependents.
AB  - OBJECTIVES: We examined the pregnancy outcomes of three ethnic groups: African
      American Blacks, non-Hispanic Whites, and Filipinos. In an attempt to reduce
      ethnic dissimilarities in parental employment and access to health care, this
      investigation compared the single-live-birth outcomes of married, adult women who
      resided in the state of Hawaii and who indicated that their spouse was on active
      duty status in the US military. METHODS: The data for this study were obtained
      from the 1979-1989 Hawaii vital-record file that provides linked live birth
      infant death information. Multiple logistic regression was used to calculate odds
      ratios for the independent effects of maternal factors on low birthweight and
      neonatal mortality. RESULTS: Significant differences in maternal age, maternal
      education, paternal education, parity, hospital of delivery, and use of prenatal
      care were observed among the ethnic groups. The results of a logistic regression
      analysis of low birthweight indicated significantly higher risks for Filipinos
      and Blacks compared with Whites. For very low birthweight, only an increased risk
      for Blacks was observed. No ethnic differences in neonatal mortality were found.
      CONCLUSIONS: This investigation revealed more comparable infant mortality
      experiences among the ethnic groups in spite of persistent birthweight
      differences.

PMID- 8259803
TI  - Custody of cocaine-exposed newborns: determinants of discharge decisions.
AB  - OBJECTIVES: Maternal cocaine use is a leading grounds for newborn foster
      placement. This study was initiated to investigate the factors that predict
      custody status of infants born to substance-abusing women. METHODS: A
      retrospective cohort design was used to study the correlates of discharge custody
      decisions for 99 consecutive infants testing positive for cocaine in a public
      hospital. RESULTS: The population was 49% Black, 40% Hispanic, and 11% other or
      unknown. Custody at discharge was to mothers (38%), other family members (25%),
      or agency foster care (36%). Placement outside the family was greater when
      mothers had prior child welfare records, in Blacks vs others, with no prenatal
      care, and when mothers were younger at their first delivery or older at the index
      birth. Denial of custody to the mother was higher with prior child welfare
      involvement, in Blacks, and when the mother did not live in her own home. Both
      models also controlled for parity, child sex, and birthweight. CONCLUSIONS:
      Earlier involvement with child welfare authorities, race, and other factors
      predict continued separation of mothers and children at newborn discharge,
      suggesting the need to reexamine current policies and practices.

PMID- 8259804
TI  - Home health clients: characteristics, outcomes of care, and nursing
      interventions.
AB  - OBJECTIVES: The purpose of the study was to provide descriptive data about the
      characteristics of home health clients, the services that nurses provide, and the
      outcomes of those services. Such data have been sparse. METHODS: This study
      examined 2403 home health clients served by four agencies in Nebraska, New
      Jersey, and Wisconsin. Demographic, health history, and clinical data were
      analyzed. The Omaha System was used as the model for describing and measuring
      data specific to clients' health-related problems, nursing interventions, and
      outcomes of care. RESULTS: The median age of home health clients was 68.6 years.
      Nurses conducted 70% of all home visits, identified 9107 client problems, and
      provided over 96,000 interventions. Between admission and dismissal, clients
      improved by at least 0.52 point on three 5-point problem-specific outcome
      subscales (Knowledge, Behavior, and Status). CONCLUSIONS: These data show
      important characteristics of home health clients in a large national sample. They
      also support the usefulness of the Omaha System in describing and quantifying
      nursing practice in the community health setting. The magnitude of positive
      client change between admission and dismissal suggests that community health
      services do make a difference.

PMID- 8259805
TI  - Cause of death in patients with end-stage renal disease: death certificates vs
      registry reports.
AB  - OBJECTIVES: The purpose of this study was to assess agreement on cause of death
      reporting in end-stage renal disease patients by comparing death certificates and
      reports to an end-stage renal disease registry. METHODS: Death certificates and
      registry reporting forms were retrieved for a random sample of 335 treated end
      stage renal disease patients who died between 1980 and 1986 in Maryland. On the
      registry form, patient death was ascribed to 1 of 22 precoded causes by the
      patient's nephrologist of record. Corresponding death certificates were coded,
      according to rules of the International Classification of Diseases, 9th edition,
      by a trained observer unaware of the registry report. Agreement was measured by
      the kappa statistic. RESULTS: Overall cause of death agreement was poor (31%),
      and varied by the following categories: renal disease (40% on death certificates
      vs 0% on registry reports), cardiovascular disease (26% vs 47%), infectious
      disease (16% vs 22%), cancer (7% vs 5%), and withdrawal from therapy (0% vs 3%).
      Agreement was higher for transplant recipients than for dialyzed patients.
      CONCLUSIONS: Death certificates and registry reports yield different descriptions
      of mortality in end-stage renal disease patients. These sources of information
      should not be used interchangeably. Improvements to International Classification
      of Diseases coding of renal diseases and the determination of the reliability and
      validity of the US Renal Data System reporting process are necessary steps in the
      development of renal disease epidemiology.

PMID- 8259806
TI  - Infectious diseases and mortality among US nursing home residents.
AB  - Data collected in the 1985 National Nursing Home Survey were analyzed to identify
      risk factors for infections and mortality and to explore their relationship in US
      nursing homes. An infection was recorded in 166,609 (14%) discharges. Risk of
      pneumonia was found to be higher among bedbound patients (54.5 vs 13.1 per 100
      discharges); urinary tract and other infections were most frequent among
      residents with indwelling catheters (6.6 vs 1.0 per 100 discharges). Residents
      with pneumonia were more likely than those with other infections to die (35% vs
      28%), or be discharged to hospitals if alive (94% vs 66%). Thus, immobility and
      catheterization were associated with infections in US nursing homes, and
      pneumonia was found to contribute to mortality.

PMID- 8259807
TI  - Nemesis revisited: tuberculosis infection in a New York City men's shelter.
AB  - In November 1990, a screening was conducted to determine the point prevalence of
      tuberculosis infection in a volunteer sample of homeless men (n = 161) living in
      a congregate shelter in New York City. Of those for whom we have results (n =
      134), 79% were positive for tuberculosis. The mean length of shelter stay from
      date of shelter entry was 31.8 months and was significantly associated with the
      tuberculosis infection rate. The findings suggest that crowded living conditions
      and the presence of a stable resident pool in crowded congregate shelters may be
      associated with transmission of tuberculosis infection.

PMID- 8259808
TI  - Antibodies to Borrelia burgdorferi and tick salivary gland proteins in New Jersey
      outdoor workers.
AB  - In 1990, a second cross-sectional study of outdoor workers (n = 758) at high risk
      for Lyme disease was conducted. A questionnaire was administered, and antibodies
      to Borrelia burgdorferi and tick salivary gland proteins (antitick saliva
      antibody, a biologic marker of tick exposure) were assayed by enzyme-linked
      immunosorbent assay. The statewide Lyme disease seroprevalence increased from
      8.1% in 1988 to 18.7% in 1990. Antitick saliva antibody seropositivity varied by
      county and was associated with measures of self-reported tick exposure. The data
      suggested that the prevalence of B. burgdorferi infection increased in New Jersey
      outdoor workers from 1988 to 1990.

PMID- 8259809
TI  - The school-based immunization survey: an inexpensive tool for measuring vaccine
      coverage.
AB  - A school-based immunization survey was conducted among the 36 Rochester, NY,
      elementary schools (n = 5584 children) to determine (1) the vaccination rates at
      2 years of age by type of primary care provider and (2) the accuracy of school
      immunization records (by comparing them with medical charts for children
      attending hospital-based clinics). These rates varied by provider type from 58%
      to 86% and were all below the national goal of 90%. In comparison with medical
      chart review, the school data had error rates of 15%; however, these errors
      occurred in both directions and were thus unbiased. School-based surveys include
      children who lack connections to the primary care system. With minimal effort
      these surveys can help identify populations in need of intervention.

PMID- 8259810
TI  - The impact of a public health nurse intervention on influenza vaccine acceptance.
AB  - Public health clients in an Ontario community 65 years of age or older were
      randomly allocated to receive an intervention by a public health nurse during a
      home visit promoting either influenza immunization or safety measures. There was
      no statistically significant differences in influenza immunization rates between
      these two groups (56.1% vs 56.6%). Men were significantly more likely to receive
      immunization.

PMID- 8259811
TI  - Neonatal tetanus in Peru: risk assessment with modified enzyme-linked
      immunosorbent assay and toxoid skin test.
AB  - We used a modified enzyme-linked immunosorbent assay (ELISA) to investigate
      tetanus immunity in 232 pregnant Peruvian women. One hundred forty-two (61.2%)
      had protective antitoxin titers (> or = 0.01 IU/mL). Protective titers correlated
      positively with the number of toxoid doses reported during the current pregnancy.
      A majority of women reporting no toxoid doses during the current pregnancy had at
      least one prenatal health care visit. We evaluated a toxoid skin test in 44 of
      the subjects, but it correlated poorly with the ELISA. The modified ELISA is a
      useful in vitro method for studying tetanus immunity in the developing world.

PMID- 8259812
TI  - HIV transmission: Women's risk from bisexual men.
AB  - The purpose of this study was to characterize the risk of human immunodeficiency
      virus (HIV) infection for men who have sex with men and to identify the risk such
      men pose to their female sex partners. The subjects were 5480 men who were tested
      for HIV between January 1987 and December 1991 and who reported having had sex
      with a man since 1977. Men who identified themselves as bisexual or straight were
      more likely to use injection drugs, had a substantial HIV seroprevalence, and
      reported many more female partners than men who identified themselves as gay. Men
      who identify themselves as bisexual pose the greatest risk to their female
      partners.

PMID- 8259813
TI  - Acculturation and gender differences in sexual attitudes and behaviors:Hispanic
      vs non-Hispanic white unmarried adults.
AB  - Understanding how acculturation and gender affect Hispanics' sexual behavior is
      needed to prevent infection with the human immunodeficiency virus. We examined
      differences in and correlates of condom use among 398 Hispanics and 540 non
      Hispanic Whites in San Francisco who were part of a random probability sample of
      unmarried adults. Hispanic women reported fewer sexual partners than all other
      groups. Condom use was low in all groups, but Spanish-speaking Hispanic women
      reported lower condom use than White women. Hispanics, generally, had poorer
      attitudes toward condoms and were less likely than non-Hispanic Whites to believe
      they could avoid acquired immunodeficiency syndrome. Hispanics need targeted
      prevention interventions.

PMID- 8259814
TI  - Inappropriate Halsted mastectomy and patient volume in Italian hospitals.
AB  - To study whether Halsted mastectomy was used only when properly indicated, a
      prospective survey was undertaken on the process of care of 985 breast cancer
      patients seen consecutively at 62 general hospitals in Northern and Central
      Italy. Overall, 79% of Halsted mastectomies were performed inappropriately. The
      procedure was less likely to be performed on more educated patients and, other
      factors considered, on those seen at hospitals with larger volume. We conclude
      that the measurement of utilization of a surgical procedure for which only a few
      appropriate indications exist may help identify important relationships between
      hospital characteristics and quality of surgical care.

PMID- 8259815
TI  - Predictors of nursing home admission in a biracial population.
AB  - Racial differences in predictors of institutionalization were studied in a
      biracial North Carolina cohort (n = 4074). During 3 years of follow-up, 8.5% of
      Whites and 6.4% of African Americans were admitted to nursing homes. African
      Americans were one half as likely as Whites to be institutionalized after
      adjustment for other risk factors. Among Whites, impaired activities of daily
      living and cognition were the strongest predictors; among African Americans,
      impaired instrumental activities of daily living and prior history of nursing
      home use were strongest. Racial differences in nursing home use were not
      explained by financial and social support or physical and cognitive impairment.

PMID- 8259816
TI  - The Behavioral Risk Factor Surveillance System questionnaire: its reliability in
      a statewide sample.
AB  - The reliability of the Behavioral Risk Factor Surveillance System questionnaire
      was assessed in a random sample of adults (n = 122) and a separate sample of
      Black and Hispanic adults (n = 200) in Massachusetts. The questionnaire was
      administered twice, 21 to 44 days apart, by telephone (210 completed
      reinterviews, 65% response rate for second administration). There were no
      statistically significant differences in the distribution of demographic or risk
      factor variables across administrations. Individual-level reliability (kappa for
      categorical variables, correlation for continuous variables) for demographic
      characteristics was more than 0.80 for White respondents and more than 0.60 for
      Black and Hispanic respondents. Employment and income were reported less
      consistently than other variables. Reliability coefficients for behavioral risk
      factors were generally above 0.70. Exceptions were variables with extreme
      distributions. These data support the use of the Behavioral Risk Factor
      Surveillance System questionnaire for surveillance and research.

PMID- 8259817
TI  - Firearms and health: the right to be armed with accurate information about the
      Second Amendment.
AB  - An organized campaign by groups such as the National Rifle Association has sought
      to convince policymakers and others that the Second Amendment to the US
      Constitution grants an unfettered right to individuals to possess any firearm,
      free from federal or state regulation. Although advocates may debate the meaning
      that should be given to the Second Amendment, under the American legal system the
      meaning of any particular constitutional provision is determined by the
      controlling precedent of Supreme Court cases. Two cases, Presser v Illinois and
      United States v Miller, remain the Supreme Court's latest word on the meaning of
      the Second Amendment. In Presser, the Court held that the Second Amendment is
      applicable only to federal, not state, laws. In Miller and subsequent federal
      cases, any Second Amendment "right" to bear arms is closely linked to the
      preservation of state militias, upholding a variety of federal gun legislation.
      Unless the Supreme Court modifies or reverses its Presser and Miller decisions,
      health advocates should understand that the Second Amendment poses no obstacle to
      even broad gun control legislation.

PMID- 8259818
TI  - Burn prevention through Weatherization Assistance Programs.

PMID- 8259819
TI  - The Northwest Center for Public Health Practice.

PMID- 8259820
TI  - Meningococcal disease in Los Angeles County, 1981 through 1990.

PMID- 8259821
TI  - Changing HIV risk behaviors: the case against pessimism.

PMID- 8259822
TI  - Measuring HIV-1 seroprevalence among English newborns: blood spot size.

PMID- 8259823
TI  - HIV and trends in cervical cancer death rates among young women.

PMID- 8259824
TI  - Illegal sales to minors and retailers' responsibility.

PMID- 8259825
TI  - The illusion of mental health.
AB  - It is argued that researchers' reliance on "objective" mental health scales and
      disregard for clinical judgment has led to many mistaken conclusions.
      Specifically, standard mental health scales appear unable to distinguish between
      genuine mental health and the facade or illusion of mental health created by
      psychological defenses. Evidence is presented indicating that (a) many people who
      look healthy on standard mental health scales are not psychologically healthy,
      and (b) illusory mental health (based on defensive denial of distress) has
      physiological costs and may be a risk factor for medical illness. Clinical judges
      could distinguish genuine from illusory mental health, whereas "objective" mental
      health scales could not. The findings call into question the conclusions of many
      previous studies that rest on standard mental health scales. They suggest new
      ways of understanding how psychological factors may influence health. Finally,
      they suggest that clinical methods (which researchers often malign) may have an
      important role to play in meaningful mental health research.

PMID- 8259826
TI  - Reinforcement is not enough: learned expectancies and infant behavior.

PMID- 8259827
TI  - "Misbehavior": a case history.

PMID- 8259828
TI  - Evolution of black yeasts: possible adaptation to the human host.
AB  - Ascomycetous black yeasts show adaptations to a wide array of environmental
      conditions. Dothideaceous black yeasts are mostly found on plant leaves, while
      among herpotrichiellaceous species there are numerous opportunists on humans.
      Factors which are of ecological significance include the presence of melanin and
      carotene, formation of thick cell walls and meristematic growth, presence of
      yeast-like phases, presence of additional forms of conidiogenesis, thermo- and
      osmotolerance, adhesion, hydrophobicity, production of extracellular
      polysaccharides, siderophores and acidic or alkaline secondary metabolites. The
      potential pathogenicity of a species is partly determined by its natural
      ecological niche. Dothideaceous black yeasts are osmotolerant rather than
      pathogenic. Herpotrichiellaceous black yeasts probably have low competitive
      ability and are found in rather special niches as secondary saprophytes, e.g., on
      bacterial mats, on other fungi or in poor environments. Some species possibly
      utilize animal vectors for dispersal.

PMID- 8259829
TI  - The distribution and taxonomic value of fatty acids and eicosanoids in the
      Lipomycetaceae and Dipodascaceae.
AB  - Using radioimmunoassay, blood platelet aggregation studies and GC-MS the
      existence of prostaglandins in the endomycetalean yeast Dipodascopsis uninucleata
      was confirmed by our group. These findings triggered the search for similar
      eicosanoids in the rest of the Endomycetales. We commenced by scanning for the
      easily detectable precursors of eicosanoids, linoleic- and linolenic acid. We
      selected two families (i.e. Lipomycetaceae and Dipodascaceae), both producing
      these precursors, for further investigation. Representative strains of the two
      families were tested for their ability to grow in the presence of 1 mM aspirin, a
      specific inhibitor of prostaglandin biosynthesis. In contrast to the
      lipomycetaceous species the dipodascaceous species were insensitive to this drug.
      These results were verified when representative strains of both families were
      investigated for their ability to produce eicosanoids from externally fed radio
      labeled arachidonic acid along an aspirin sensitive pathway. Thin layer
      chromatography of culture extracts, followed by autoradiography, showed that
      while none of the Dipodascaceae produced aspirin sensitive arachidonic acid
      metabolites, the members of the Lipomycetaceae tested positive for these
      metabolites. These findings supported the separation of the lipomycetaceous yeast
      Dipodascopsis from the Dipodascaceae. The findings also correlate with the
      delimitation of these yeasts in two families (i.e. Dipodascaceae and
      Lipomycetaceae). Further investigation indicated that prostaglandin production by
      the genus Dipodascopsis is mainly associated with ascosporogenesis. Thin layer
      chromatography of cell extracts from Dipodascopsis tothii, followed by
      scintillation counting, indicated the presence of PGF2 alpha and PGE2 during
      ascosporogenesis.

PMID- 8259830
TI  - Catabolism of benzene compounds by ascomycetous and basidiomycetous yeasts and
      yeastlike fungi. A literature review and an experimental approach.
AB  - A literature review is given on growth of yeasts on benzene compounds and on the
      catabolic pathways involved. Additionally, a yeast collection was screened for
      assimilation of phenol and 3-hydroxybenzoic acid. Fifteen ascomycetous and
      thirteen basidiomycetous yeast species were selected and were tested for growth
      on 84 benzene compounds. It appeared that 63 of these compounds supported growth
      of one or more yeast species. The black yeast Exophiala jeanselmei assimilated 54
      of these compounds. The catechol branch of the 3-oxoadipate pathway and its
      hydroxyhydroquinone variant were involved in phenol and resorcinol catabolism of
      ascomycetes as well as of basidiomycetes. However, these two groups of yeasts
      showed characteristic differences in hydroxybenzoate catabolism. In the yeastlike
      fungus E. jeanselmei and in basidiomycetes of the genera Cryptococcus,
      Leucosporidium and Rhodotorula, the protocatechuate branch of the 3-oxoadipate
      pathway was induced by growth on 3- and 4-hydroxybenzoic acids. In three
      Trichosporon species and in all ascomycetous yeasts tested, 4-hydroxybenzoic acid
      was catabolyzed via protocatechuate and hydroxyhydroquinone. These yeasts were
      unable to cleave protocatechuate. 3-Hydroxybenzoic and 3-hydroxycinnamic acids
      were catabolized in ascomycetous yeasts via the gentisate pathway, but in
      basidiomycetes via protocatechuate. Incomplete oxidation of phenol, some
      chlorophenols, cresols and xylenols was observed in cultures of Candida
      parapsilosis growing on hydroquinone. Most compounds transformed by the growing
      culture were also converted by the phenol monooxygenase present in cell-free
      extracts of this yeast. They did not support growth. The relationship between the
      ability of ascomycetous yeasts to assimilate n-alkanes, amines and benzene
      compounds, and the presence of Coenzyme Q9 is discussed.

PMID- 8259831
TI  - Electrophoretic karyotyping as a taxonomic tool in the genus Saccharomyces.
AB  - The electrophoretic karyotypes of strains of the ten species of the yeast genus
      Saccharomyces (sensu Vaughan-Martini & Martini 1992) were determined by the CHEF
      (contour-clamped homogeneous electric field) system of pulsed field gel
      electrophoresis. The number of bands was found to vary from 6 to 17 and the
      calculated molecular weights of haploid genomes ranged from 7.9 to 14.6 Mbp. The
      type strains of S. exiguus and the four species of the Saccharomyces sensu
      stricto complex (S. bayanus, S. cerevisiae, S. paradoxus and S. pastorianus) have
      genomes comprised of chromosomes of all three size classes: light (< 500 kb),
      medium (500-1000 kb) and heavy (> 1,000 kb). Saccharomyces kluyveri DNA has only
      heavy bands, while the remaining species exhibit medium and heavy chromosomes.
      When more than one strain of each species was examined, it was seen that while
      the species S. bayanus, S. castellii, S. cerevisiae, S. kluyveri, S. paradoxus
      and S. pastorianus showed uniform karyotypes, S. dairensis, S. exiguus, S.
      servazzii and S. unisporus comprise heterogeneous taxa.

PMID- 8259832
TI  - The use of karyotyping in the systematics of yeasts.
AB  - The use of electrophoretic karyotyping in systematics of yeasts is discussed. New
      data are provided on the karyotypes of the medically important fungi Hortaea
      werneckii, Filobasidiella (= Cryptococcus) neoformans, and Malassezia species.
      Hortaea werneckii has twelve to eighteen bands of chromosomal DNA, ranging in
      size between 500 and 2300 kb. The karyotypes of Filobasidiella neoformans consist
      of seven to fourteen bands of chromosomal DNA. The varieties neoformans and
      bacillispora cannot be separated by their karyotypes, and no obvious correlation
      was found with serotypes, geography or habitat. All strains of Malassezia
      pachydermatis studied have similar karyotypes consisting of five bands, whereas
      in M. furfur, four different karyotypes are prevalent. However, each of these
      karyotypes is stable.

PMID- 8259833
TI  - Systematics of the ascomycetous yeasts assessed from ribosomal RNA sequence
      divergence.
AB  - Extent of divergence in partial nucleotide sequences from large and small subunit
      ribosomal RNAs was used to estimate genetic relationships among ascomycetous
      yeasts and yeastlike fungi. The comparisons showed four phylogenetically distinct
      groups comprised of the following taxa: Group 1. The budding yeasts
      Saccharomyces, Saccharomycopsis, Debaryomyces, Metschnikowia, Saturnospora, and
      Lipomyces, and the yeastlike genera Ascoidea, Cephaloascus, Dipodascus,
      Dipodascopsis, and Galactomyces; Group 2. Eremascus, Emericella and Ceratocystis;
      Group 3. Taphrina and Protomyces; Group 4. Schizosaccharomyces. Because of the
      genetic relationships indicated by sequence analysis, Group 1 taxa are retained
      in the order Endomycetales, and Schizosaccharomyces is retained in the
      Schizosaccharomycetales Prillinger et al. ex Kurtzman.

PMID- 8259834
TI  - Phylogenetic relationships of Cryptococcus neoformans and some related
      basidiomycetous yeasts determined from partial large subunit rRNA sequences.
AB  - The genus Cryptococcus was found to be heterogeneous on the basis of partial rRNA
      sequences. The human-pathogenic species C. neoformans, comprising 4 serotypes and
      having Filobasidiella neoformans and F. bacillispora as teleomorphs, was found at
      a relatively large distance from Filobasidium. Serotypes B and C had identical
      sequences, while in A and D they were different, with D closer to B and C than to
      A. Filobasidiella depauperata, which lacks a yeast-like anamorph, clustered with
      F. neoformans. The genus Filobasidium was clearly separated from Filobasidiella
      and clustered with C. albidus, C. kuetzingii, C. gastricus, C. lupi, C.
      vishniaciae, C. bhutanensis, C. aerius, C. terreus and C. ater. The latter may
      represent the anamorph of Filobasidium elegans. The orange to red species of
      Cryptococcus, as well as C. aquaticus and C. yarrowii, were found completely
      unrelated with these taxa, C. macerans being affiliated to Cystofilobasidium
      capitatum. The genus Trichosporon was found relatively homogeneous; it includes
      C. humicola, C. curvatus and the filamentous species Hyalodendron lignicola.
      Cryptococcus flavus and C. dimennae probably belong to the Tremellales, though
      distances between these species are large. The positions of C. laurentii and C.
      luteolus remains to be determined.

PMID- 8259835
TI  - The expanding realm of ballistosporous yeasts.
AB  - The recent progress in the systematics of ballistosporous yeasts is discussed.
      The extensive isolation studies carried out in the last decade resulted in a
      marked increase in the number of ballistosporous yeast species which now number
      nearly fifty. The increased number of species has expanded the complexity of
      taxonomic properties in the following ways: expansion of the range of mol% G+C of
      nuclear DNA to 39-68.5, thus overlapping that of all basidiomycetous yeasts;
      increased complexity of conidiogenesis with the finding of the genera
      Ballistosporomyces and Kockovaella. Based on partial sequencing of 18S ribosomal
      RNA (positions 1451-1618 in Saccharomyces cerevisiae), it is suggested that mode
      of conidiogenesis has little value for defining genera. Consequently,
      ballistosporous yeasts merely represent the "ballistosporous stage" of various
      taxa which cover the whole evolutionary spectrum of basidiomycetous yeasts. The
      importance of continuing isolation of ballistosporous yeasts is stressed, which
      together with molecular studies, will aid further progress in the systematics of
      basidiomycetous yeasts.

PMID- 8259836
TI  - Phylogenetic analysis of basidiomycetous yeasts by means of 18S ribosomal RNA
      sequences: relationship of Erythrobasidium hasegawianum and other basidiomycetous
      yeast taxa.
AB  - The basidiomycetous yeast genus Erythrobasidium Hamamoto, Sugiyama & Komagata,
      based on the type species E. hasegawianum Hamamoto et al., is characterized by
      filobasidiaceous basidia and the Q-10 (H2) system as its major ubiquinone. It is
      tentatively placed in the Filobasidiaceae. The molecular characterization is
      based on 18S ribosomal RNA sequence comparisons among the basidiomycetous yeasts,
      and the ultrastructural characterization on the cell wall and hyphal septal pores
      in E. hasegawianum clearly indicate a close relationship with the teliospore
      forming yeasts Rhodosporidium toruloides and Leucosporidium scottii. Our
      molecular phylogeny with statistical analysis suggests that the existing
      taxonomic system of basidiomycetous yeasts, based primarily on the morphology of
      basidia including the teliospores (probasidia), should be revised.

PMID- 8259837
TI  - Kluyveromyces: systematics since 1970.
AB  - The taxonomy of Kluyveromyces has been the object of intense study since van der
      Walt's (1970) monograph. This is an account of the major developments and the
      classification to be adopted in the 4th edition of The Yeasts, a Taxonomic Study.
      The guiding principles that will be followed in eventual revisions of the genus
      are presented.

PMID- 8259838
TI  - [Epidemiological characteristics of cancer in Asia].
AB  - Most nations in Asia are developing countries. Recently, in developed and
      developing countries cancer has become an important public health problem. This
      paper reviews the characteristics of cancer epidemiology in Asia and describes
      the cancer mortality, cancer incidence, migrant studies and current status of
      secondary prevention for cancer in several Asian countries. Unfortunately,
      mortality statistics and data on cancer incidence are frequently not available or
      not very accurate in most developing countries. Greater cooperation is hoped for
      between Japan and other Asian countries in order to obtain more exact information
      on cancer statistics and to draw up an accurate cancer map.

PMID- 8259839
TI  - [An outline of 5-HT3 receptor antagonists (2)--In clinical applications].
AB  - This paper described an outline of clinically applications of 5-HT3 receptor
      antagonists, mainly on ondansetron, which control nausea and vomiting associated
      with cancer chemotherapy. Clinically, 5-HT3 receptor antagonists demonstrated
      significantly superior antiemetic effects to metoclopramide which has been
      prescribed for relatively long time. The response rates for granisetron and those
      for ondansetron were different due to the different categorical scales. However,
      when the same scale was applied, similar efficacies have been observed.
      Introduction of the tablet form may well broaden the clinical applications.
      Considering the highly evaluated safety, 5-HT3 receptor antagonists, from the
      viewpoints of clinical usefulness and safety, seems to be useful drugs for
      controlling nausea and vomiting associated with cancer chemotherapy.

PMID- 8259840
TI  - [The effect of thyroid hormone on thyroid cancer growth].
AB  - Differentiated thyroid cancer, like breast cancer, prostatic cancer, and
      endometrial cancer of the uterus, is well known to be hormone sensitive.
      Experimental investigations have demonstrated that differentiated thyroid cancer
      cells have TSH (thyroid-stimulating hormone) receptor on the plasma membrane and
      that the growth regulation of differentiated thyroid cancer depends upon TSH.
      Therefore, suppression of TSH with thyroid hormone is rational for the treatment
      of recurrent thyroid cancer. Recurrent differentiated thyroid cancers reportedly
      cause regression in response to thyroid hormone administration, but the outcome
      of adjuvant therapy with thyroid hormone after operation for differentiated
      thyroid carcinoma is controversial. It is very difficult to analyze the
      difference in survival rate between the postoperative patient with and without
      thyroid hormone, because of the excellent postoperative survival rate of
      differentiated thyroid cancer patients. Further clinical studies and laboratory
      investigations about TSH suppression in adjuvant therapy for differentiated
      thyroid cancer are necessary to elucidate the impact of thyroid hormone on
      survival after operation.

PMID- 8259841
TI  - [Recent development of endocrine treatment for breast cancer--new drugs and new
      treatment methods using tamoxifen].
AB  - The characteristics and clinical efficacies of new hormonal drugs and new
      treatment methods for breast cancer using tamoxifen (TAM) were described. The new
      anti-estrogens, such as trioxifen, toremifene and droloxifen, have equal or
      better clinical efficacy than TAM. They showed a high response rate in
      postmenopausal patients with no previous treatment or estrogen receptor positive
      tumors. They were occasionally effective for patients who relapsed after TAM
      treatment. Pure anti-estrogen ICI 164, 384, with fewer estrogenic agonistic
      properties than TAM, and anti-estrogen TAT-59, which has been developed in Japan,
      are under clinical investigation. Luteinizing hormone-releasing hormone agonists,
      such as leuprolide, buserelin, triptrelin and goserelin, are available for
      premenopausal patients, and showed a 37% response rate on average. The pure
      aromatase inhibitors, such as 4-hydroxyandrostenedione and CGS 16, 949 A, are
      available for postmenopausal patients, and showed 30% and 17% response rates on
      average, respectively. The new pure aromatase inhibitor ZD-1033 is also under
      clinical investigation. TAM or toremifene as well as the calcium antagonist
      verapamil were proved to overcome the multiple anticancer drug resistance caused
      by P-glycoprotein. Clinical studies for breast cancer using high-dose TAM as a
      potential modulator of drug resistance have already been started in Europe and
      the United States. Chemoprevention of breast cancer using TAM, which started in
      the U.S., was described.

PMID- 8259842
TI  - [Hormonotherapy for prostate cancer].
AB  - Since the report by Dr. Huggins, the Nobel prize winner, hormonotherapy has been
      a predominant treatment modality for prostate cancer for decades around the world
      because of its anti-cancer effect and simplicity. In the 1960's, the Veterans
      Administration Co-operative Urological Research Group (VA CURG) in the U.S.A.
      claimed that synthetic estrogen had significant adverse effects such as cardio
      vascular complications, which dissipated the merits of estrogen. They reported
      that a group of prostate cancer patients who underwent estrogen therapy showed
      the same survival as a no treatment group. The normal prostate gland is dependent
      on androgen for its development, growth and function as well as prostate cancer.
      Ninety to 95% of androgens are synthesized in testicular Leydig cells under the
      control of the pituitary-gonadal axis, and the remaining androgens come from the
      adrenal glands. At any point along the axis from the hypothalamus to the prostate
      cell nuclei, androgen action on the prostate gland can be inhibited. Castration
      eliminates Leydig cells and estrogen reduces the serum testosterone level by
      negative feedback to the pituitary gland. Because of the significant side effects
      of estrogen and the mental injury brought about by castration, LH-RH analogue
      could have received great popularity. But impotence is still a major consequence
      of this drug. For less invasive and more economical treatment modalities for
      prostate cancer, effective anti-androgenic drugs which do not cause impotence
      must be developed. And the mechanism of androgen independence must be elucidated
      to obtain a more effective and complete hormonotherapy for prostate cancer.

PMID- 8259843
TI  - [Hormonal therapy in endometrial cancer].
AB  - Hormonal agents have been used to treat endometrial cancer since the early 1960s.
      The response rate for patients with advanced or recurrent endometrial cancer
      subjected to gestagen therapy has been reported to be about 30%. However, the
      analysis of the action mechanism of gestagen on endometrial cancer is not
      complete. Since oral administration of high dose MPA has begun, thrombosis has
      been reported as an uncommon but severe side effect. The risk factors for
      thrombosis in patients having gestagen therapy were clarified in the report
      published by the Ministry of Welfare in 1992. This report emphasized the
      importance of patient selection for gestagen therapy and cautious management.
      Besides gestagen therapy, antiestrogen therapy has been tried for the treatment
      of endometrial cancer. However, tamoxifen therapy was not so effective compared
      with gestagen. Moreover, antiestrogen-gestagen combination therapy and chemo
      endocrine therapy are on trial recently. These trials are attempts to find a more
      effective regimen for the treatment of endometrial cancer. A recent theme in the
      study of hormonal therapy is basic investigation concerning the effect of MPA
      upon the action of growth factor and oncogene expression in endometrial cancer
      cells. These studies may lead to a molecular biological explanation of the action
      mechanism of gestagen therapy in future.

PMID- 8259844
TI  - [Medical treatment of malignant hypercalcemia].
AB  - Hypercalcemia is one of the life-threatening paraneoplastic syndromes and urgent
      medical treatments are needed since malignant hypercalcemia progresses very
      rapidly. The intravenous administration of sufficient quantities of isotonic
      saline sometimes with loop diuretic agents is the first and fundamental step in
      the management of malignant hypercalcemia. As hormonal therapeutic agents for
      malignant hypercalcemia, calcitonin and/or glucocorticoid are the usual
      candidates. Calcitonin exerts calcium-lowering effects both through its direct
      inhibitory effect on osteoclastic bone resorption and prevention of calcium
      reabsorption from renal tubulus. Among the anticalcemic agents available,
      calcitonin has the most rapid onset of action; the hypocalcemic effects appear
      within a few hours after administration. But continued usage diminishes its
      effect which is called the "escape phenomenon". The usual dosage of calcitonin is
      80-160 unit/day. Glucocorticoid alone has sometimes calcium-lowering effects for
      malignant hypercalcemia, even in the case of solid cancer such as lung cancer,
      though the mechanism is not clear. In lymphocytic proliferative disorders, a
      direct inhibitory effect on the proliferation of malignant cells accounts for the
      calcium-lowering effects. Glucocorticoid is known to prolong the calcium-lowering
      effect of calcitonin. So, the combination of calcitonin and glucocorticoid is the
      most effective hormonal treatment for malignant hypercalcemia. Calcitonin is used
      for initial several days and glucocorticoid (30-40 mg/day) is continued along
      with calcitonin from the beginning of the treatment. Most effective and safe
      hypocalcemic agents for malignant hypercalcemia are the newly developed
      bisphosphonate compounds, which are not yet available in Japan. These agents
      interact chemically with hydroxyapatite on the bone surface and prevent
      osteoclastic function and activity. According to the data of our own
      investigation, pamidronate, one of the relatively new generation of
      bisphosphonates, showed clearly hypocalemic effects for malignant hypercalcemia
      due to various kinds of malignancy by one intravenous administration (30-60 mg)
      without any adverse effect. In near future, the combination of calcitonin and
      bisphosphonates will also be the most effective medical management for malignant
      hypercalcemia in Japan.

PMID- 8259845
TI  - [Efficacy of FEM (5-fluorouracil, epirubicin, mitomycin C) therapy for resected
      advanced gastric cancer. Ehime Gastric Cancer Study Meeting].
AB  - Between April 1990 and March 1991, postoperative adjuvant chemotherapy for
      resected gastric cancer employing 5-fluorouracil, epirubicin and mitomycin C
      (FEM) was performed. Forty-two patients subjected to the therapy were considered
      to have positive serosal invasion and underwent curative operation. FEM therapy
      consisted of intraoperative intraperitoneal administration of mitomycin C (0.3
      0.4 mg/kg) combined with 8 cycles of intravenous bolus injection of epirubicin
      (20 mg/body) every 2-3 weeks which was started 2 weeks after the operation. Daily
      oral administration of 5-fluorouracil (150-200 mg/body) was started 2 weeks after
      the operation and continued for more than 6 months. Thirty-four of the 42 cases
      were assessable. Major adverse effects were nausea, vomiting, and general
      fatigue. There were no cardiovascular symptoms. The cumulative two-year survival
      rate was 74.2%, and follow-up was still under way at this writing.

PMID- 8259846
TI  - [A comparative study among ftorafur, ftorafur plus tamoxifen, and tamoxifen in
      adjuvant therapy for breast cancer. The Chubu Cooperative Study Group of Adjuvant
      Chemoendocrine Therapy for Breast Cancer, Japan].
AB  - A randomized study assessing the efficacy of three treatment of ftorafur (FT),
      ftorafur plus Tamoxifen (TAM), and Tamoxifen in patients diagnosed as having
      stage II (N1b) or stage III breast cancer was carried out at 90 institutions in
      the Chubu district of Japan. After 10 mg of MMC administration on the day of
      surgery and the next day, patients were allocated to one of three treatments: FT
      600 mg/day for 2 years, FT 600 mg/day plus TAM 20 mg/day for 2 years, or TAM 20
      mg/day for 2 years. A total of 647 cases were analyzed. No significant
      differences were observed in the 5-year disease-free survival rates or in the 5
      year survival rates. In the stratified analysis, however, a beneficial effect of
      adding FT to TAM was observed in the patients with ER-positive tumors in the 5
      year survival rate, and FT plus TAM treatment was favorable compared with the
      other two treatments for postmenopausal patients with ER-positive tumors.

PMID- 8259847
TI  - [Weekly hepatic arterial infusion of high-dose 5-FU for liver metastases from
      colorectal cancer].
AB  - A study was conducted on weekly infusion of high-dose 5-FU by way of the hepatic
      artery for liver metastases from colorectal cancer. In the evaluation of 13
      cases, no CR and 6 PR were observed. The response rate was 46.2%, 1-year survival
      was 73% and 1.5-year survival was 42%. No patients suffered from major side
      effects. Two patients had ileus, which was controllable by supportive care with
      intravenous hyperalimentation, and was caused by peritoneal dissemination of
      cancer. In conclusion, this regimen was relatively safe, effective, and useful
      for improving the quality of life of patients, compared with other regimens. How
      to control extrahepatic metastases in addition to this regimen is a subject for
      forthcoming study.

PMID- 8259848
TI  - [Efficacy of 48-hour infusion of 5-fluorouracil for gall bladder cancer].
AB  - Usefulness of an adjuvant chemotherapy for 23 patients who had undergone "non
      curative" resection for adenocarcinomas of the gallbladder was investigated.
      Patients were divided into two groups: Group A (16 patients) was given MF
      (mitomycin C 6 mg/m2, 5-fluorouracil 250 mg/body) by injection on the 2nd and 9th
      postoperative day and received orally Tegafur 600 mg/day and PSK 3 g/day. Group
      B(7 patients) was treated weekly with a 48-hour infusion of 5-FU (1,000 mg/m2/24
      hours), for 6 weeks and leucovorin (30 mg/body) was given for 2 hours prior to 5
      FU infusion. The results were evaluated by the Kaplan-Meier method. Response rate
      of anti-tumor was 0% in Group A and 14.3% in Group B, including: PR, 1 and NC, 6
      cases. The 50% survival time was 230 days in group A and 471 days in group B (p =
      0.0008). The results suggest that treatment with 5-FU and LV is effective for
      gallbladder cancer.

PMID- 8259849
TI  - [Initial anthracycline-based chemotherapy without radiotherapy in patients older
      than 70 years with localized lymphoma arising from Waldeyer's ring].
AB  - Between July 1982 and November 1992 twenty-six patients older than 70 years with
      localized stage of non-Hodgkin's lymphoma (NHL) arising from Waldeyer's ring were
      treated with initial chemotherapy consisting of anthracycline-based combination
      chemotherapies without regional radiotherapy in Saitama Cancer Center and Chiba
      Cancer Center. Patients with stage I-II were eligible for this study. There were
      9 men and 17 women, ranging in age from 70 to 86 years with a median age of 77.
      Eight patients were aged over 80. The initial chemotherapy consisted of 400 mg/m2
      of cyclophosphamide iv on day 1, either 40 mg/m2 of adriamycin or 40 mg/m2 of
      epirubicin iv on day 1, 2.0 mg/m2 of vindesine iv on day 1 and 40 mg/m2 of
      prednisolone po for 5 days. This combination chemotherapy was repeated every 4
      weeks and given 6-10 cycles. There were 4 cass of stage I disease and 22 cases of
      stage II disease. Histologic subtypes were follicular large (1 case), diffuse
      large (16 cases), diffuse mixed (4 cases), and diffuse medium (4 cases). A
      complete response was obtained in 23 (88%) of the 26 patients. The median courses
      of chemotherapies in complete responders were 6 (range, 2-10). There were 7
      recurrences among the 23 responders. The complete response was well sustained
      with an actuarial relapse-free survival of 59% at 5 years. To date 9 patients
      expired, four after a recurrence, four under complete remission and the remaining
      one without attaining CR. The survival curve of all patients became flat at 56
      months and was well sustained with an actuarial survival of 34%.

PMID- 8259850
TI  - [Studies of prognostic factor and chemotherapeutic effect of epithelial ovarian
      cancer using Cox's proportional hazard model].
AB  - To make clear the prognostic factor and chemotherapeutic effect of epithelial
      ovarian cancer, a multiple-center study involving 22 hospitals in Japan was
      conducted using Cox's proportional hazard model. A total of 1,181 cases were
      reviewed. Clinical stage, histologic type, and residual tumor diameter were
      significant prognostic factors, but the degree of tissue differentiation was not.
      The effect of remission induction chemotherapy was assessed with or without CDDP,
      and a distinct prognostic difference was noted. Among the patients receiving CDDP
      + ADM + other chemotherapeutic agents (PA group), CDDP + other chemotherapeutic
      agents (PO group) and CDDP only (P group), the prognosis of the PO group was
      better than for the P group. The long-term prognosis improving effect of
      chemotherapy was assessed. Neither maintenance chemotherapy based on oral
      administration of pyrimidine fluoride nor immunotherapy had any long-term
      prognosis improving effect, while intermittent chemotherapy based on CDDP
      resulted in improved prognosis.

PMID- 8259851
TI  - [A new application of immunoconjugate to reduce the local recurrence of
      colorectal cancer].
AB  - To examine whether or not immunoconjugate-A7-NCS can contribute for the reduction
      of local recurrence of colorectal cancer, the present study was undertaken. The
      study included examination of local retension, lymphatic delivery and inhibitory
      effect on tumor development after local administration of A7-NCS. The result
      showed that locally injected A7-NCS showed a high local retension, a high
      regional lymph node accumulation and a high inhibitory effect on tumor
      development. This finding indicates that A7-NCS can be a new promising tool for
      reducing the local recurrence of colorectal cancer.

PMID- 8259853
TI  - [Antiemetic efficacy of granisetron in pediatric cancer treatment--(2).
      Comparison of granisetron and granisetron plus methylprednisolone as antiemetic
      prophylaxis].
AB  - A crossover clinical trial was carried out to compare the effectiveness and
      safety of granisetron alone (40 micrograms/kg) with that from a combination of
      granisetron plus methylprednisolone (MPL, 10 mg/kg) for control of emesis and
      vomiting induced by anticancer drugs in children with cancer. Complete control of
      emesis and vomiting were achieved in 95% (19/20 cases) of patients receiving the
      combination compared to 85% (17/20 cases) of patients receiving granisetron
      alone. There were no clinical toxicities or side effects in either treatment
      group. These data indicated that the combination of granisetron plus MPL was
      superior for control of emesis and vomiting in children receiving cytostatic
      anticancer drugs.

PMID- 8259852
TI  - [Antitumor activity of various cytostatics in mice bearing murine advanced
      tumors].
AB  - Antitumor activities of cytostatics such as 5-FU, 5'-DFUR, cyclophosphamide
      (CPA), ACNU, CDDP, mitomycin C (MMC) and doxorubicin (DXR) were compared in mice
      bearing four different murine-tumor models at two different stages of the tumor
      growth. All cytostatics tested suppressed the tumor growth in most of the four
      tumors, colon 26 carcinoma, UV 2237 fibrosarcoma, Ehrlich carcinoma and Meth A
      fibrosarcoma, when the tumor sizes were small (early transplant). When given to
      mice bearing advanced tumors, 5-FU, CDDP, MMC and DXR were effective only at the
      higher doses, showing toxicity. In contrast, 5'-DFUR was equally effective
      against both most of early and advanced tumors except for advanced Meth A against
      which higher doses of 5'-DFUR were needed. CPA and ACNU equally suppressed the
      growth of early transplant and advanced tumors of Meth A, although higher doses
      were needed against advanced tumors of three others. 5'-DFUR was also effective
      against tumor cachexia (colon 26) and spontaneous metastasis (Lewis lung
      carcinoma), which are characteristically observed in mice bearing advanced
      tumors. CPA also showed an anticachectic activity, though the activity was weaker
      than that of 5'-DFUR. These results suggest that 5'-DFUR and CPA can be used in
      both intensive and adjuvant chemotherapies.

PMID- 8259854
TI  - [A case of advanced gastric cancer responding well by preoperative chemotherapy
      with CDDP and MMC].
AB  - A 35-year-old female who suffered advanced gastric cancer (classified Borrmann
      type 3) with para-aortic lymph nodes swelling received chemotherapy
      preoperatively. These lymph nodes, which could be detected by abdominal CT scan,
      were highly suspected of metastasis from gastric cancer. The regimens of
      neoadjuvant chemotherapy were Mitomycin C (MMC) 8 mg/m2 and Cis-platinum (CDDP)
      75 mg/m2, administered intravenously as one course. After she was given these two
      courses, we performed total gastrectomy, pancreatico-splenectomy, and lymph
      adenectomy curatively. The patient has been maintained in an outpatient clinic
      for one and half years without any evidence of recurrence.

PMID- 8259855
TI  - [A case of early gastric cancer with Virchow's node metastasis, effectively
      treated by high dose of UFT].
AB  - We report a case of early gastric cancer with Virchow's node metastasis. The
      patient underwent partial gastrectomy and postoperative immunochemotherapy using
      MMC, 5'-DFUR and PSK, which reduced the Virchow's node. Three years after
      surgery, we found metastases to the left subclavicular and axillary nodes other
      than the Virchow's node. Then UFT was administered orally at 600 mg/day, and the
      metastatic nodes diminished, then vanished. The patient is alive nearly five
      years after surgery.

PMID- 8259856
TI  - [Four cases of advanced adenocarcinoma showing marked response to EAP (etoposide,
      ADM, CDDP) treatment].
AB  - Four cases of unresectable adenocarcinoma due to multiple metastasis were treated
      by EAP (etoposide, ADM, CDDP). The first was a 49-year-old male with gall bladder
      cancer, who was admitted to the hospital with metastatic umbilical tumor and
      intraabdominal dissemination. After 2 courses of treatment, the tumor was
      significantly decreased and the dissemination was diminished. The second was a 42
      year-old female of breast cancer, involving lung, adrenal gland and bone
      metastasis. After 2 courses of treatment, all metastasis responded remarkably.
      Case 3 was a 42-year-old female with recurrent rectal cancer. Her lung metastasis
      completely disappeared after EAP treatment. Case 4 was a 42-year-old breast
      cancer patient with multiple liver metastasis, who also exhibited a remarkable
      response. In spite of severe side effects, EAP treatment was remarkably effective
      in all four cases of unresectable advanced adenocarcinoma.

PMID- 8259857
TI  - [Successful treatment of recurrent multiple lung metastasis from colon cancer
      with combination chemotherapy using methotrexate, 5-fluorouracil, and high-dose
      leucovorin: a case report].
AB  - A 66-year-old man, who had received sigmoidectomy for sigmoid cancer in 1985, was
      diagnosed as having multiple lung and liver tumors in September 1988. When celiac
      angiography was performed, recurrent liver metastases from sigmoid cancer were
      suspected and he received a transarterial embolism with ADM 30 mg and MMC 20 mg.
      In addition, he was treated with a sequential chemotherapy with methotrexate
      (MTX), 1,200 mg intravenously (6 h-infusion) followed by 5-fluorouracil (5-FU),
      600 mg/m2/day and leucovorin, 300 mg/body/day in continuous infusion for 5 days
      from day 2 with concomitant oral administration of dipyridamole (300 mg/day) over
      14 days. Treatment was repeated every 28 days for two courses. For the third
      course, administration of only 5-FU, leucovorin and dipyridamole was performed.
      As a result, the size of pulmonary lesions was prominently reduced on computed
      tomography. Although mucositis, anal erosion, diarrhea and thrombocytopenia were
      noted, no severe side effects were observed. This sequential chemotherapy appears
      useful for metastatic lesions from colon cancer.

PMID- 8259858
TI  - [A case of giant hepatocellular carcinoma effectively treated by UFT].
AB  - An 84-year-old woman who suffered from heart failure was admitted to our hospital
      in July 1991. We found a hepatocellular carcinoma, of about 9 cm in diameter in
      her right liver lobe. The patient could not be operated on, TAE and PEIT, so she
      has been administered UFT (300 mg/day) orally every day. After seven months,
      observing the patient by means of computerized tomography, we noticed that the
      tumor had decreased in size until only a small cyst was left. PIVKA-II reached
      the normal range (under 0.063 AU/ml) from its previous level (42.940 AU/ml). She
      has maintained a good state of health for about two years now. This is considered
      a very rare case in which chemotherapy proved to be completely effective, and the
      patient has survived for a long time afterwards.

PMID- 8259859
TI  - [A new approach to intra-arterial infusion chemotherapy for breast cancer].
AB  - To perform intra-arterial infusion chemotherapy for breast cancer, we cannulated
      the internal thoracic and lateral thoracic arteries, respectively. In the past,
      we could catheterize the former vessel only 43% of the time using gross
      observation, but now we can do so 100% of the time with an operating microscope
      apparatus. It was selectively done in the latter vessel through the brachial
      artery after the Seldinger method. An 82-day-long intra-arterial chemotherapy
      could be continued without any restriction in the patient's daily life, and the
      tumor decreased in size considerably. Nevertheless, intra-arterial preservation
      of the catheter and administration of anticancer drugs decrease local blood flow
      and produce thromboangitis, resulting in an extremely hypovascular state of tumor
      lesion. These changes, observed both angiographically and fluorographically, pose
      problems which must be resolved for long-term intra-arterial infusion
      chemotherapy.

PMID- 8259860
TI  - [A case of gastric amyloidosis developing into Bence-Jones type multiple myeloma,
      treated effectively by cyclo-VAMP chemotherapy].
AB  - A 65-year-old man was admitted because of bleeding from gastric ulcer. A massive
      deposition of AL lambda type amyloid proteins in the gastric lesion was found.
      There were a few Bence-Jones (BJ) proteins in the urine, but serum M proteins and
      bone lesions were not found. Bone marrow puncture showed no dysplastic change of
      plasma cells. Moreover, there were no amyloid proteins deposited anywhere in the
      digestive tract examined, except for the stomach, nor were they found in the bone
      marrow, prostata, liver or kidney. Gastric amyloidosis was diagnosed. Gastrectomy
      was performed because of uncontrollable bleeding. Sixteen months later, bone
      swelling occurred in the sternoclavicular joint and the 3rd rib. At that time,
      plasma cells with dysplasia and increasing levels of urine BJ protein were
      revealed. BJ type multiple myeloma was finally diagnosed. For remission
      induction, cyclo-VAMP chemotherapy was given in 3 courses. Decreased levels of
      urine BJ protein, diminished bone lesion, normalization of bone marrow and fewer
      amyloid deposits were seen, and partial response was obtained. The patient is
      well with no signs of recurrence evident 42 months after treatment. This is an
      interesting case of initial gastric amyloidosis that developed into BJ type
      multiple myeloma and was effectively treated with cyclo-VAMP chemotherapy.

PMID- 8259861
TI  - [M-VAC therapy in a patient with ureteral carcinoma accompanied by chronic renal
      failure].
AB  - A 63-year-old man with recurrence of ureteral cancer accompanied by chronic renal
      failure was given M-VAC therapy. Twenty mg of methotrexate was infused on the
      first day, and 30 mg of cisplatin was infused for one hour at two hours before
      dialysis on the second day. The total-CDDP level declined in two exponential
      curves. The half-life of the first phase was 75 minutes and that of the second
      phase was very long. The free-CDDP level was decreased rapidly and near the level
      for quantitative analysis after dialysis. Three mg of CDDP was eliminated by
      dialysis. Seventy-two hours after administration, the MTX level was 0.27 microM,
      which was at the high-risk level of high-dose therapy. In conclusion, it is
      considered that CDDP and MTX can be given to a patient with chronic renal
      failure. However, it is necessary to determine the MTX serum level, even after
      very low dosages, and to adjust the leucovorin rescue therapy accordingly.

PMID- 8259862
TI  - [Combination chemotherapy with carboplatin and etoposide against lung
      adenocarcinoma in a patient undergoing hemodialysis: a case report].
AB  - A 60-year-old male with chronic renal failure undergoing hemodialysis was treated
      with combination chemotherapy with carboplatin and etoposide against stage IV
      adenocarcinoma of the lung. Three hundred mg/m2 of carboplatin on day 1, and 50
      mg/m2 of etoposide on days 1 and 3 were injected intravenously before
      hemodialysis. Pharmacokinetic results revealed that carboplatin was dialyzed. No
      severe side effects were observed. These observations suggest that combination
      chemotherapy with carboplatin and etoposide seemed to be applicable to the
      patients with chronic renal failure undergoing hemodialysis.

PMID- 8259863
TI  - [An epidemic of Clostridium difficile colitis in patients with cancer: role of
      cancer chemotherapy and nosocomial infection in the pathogenesis].

PMID- 8259864
TI  - [A double-blind comparison of FUra plasma concentration by oral (UFT) vs
      continuous intravenous infusion (5-FU)].

PMID- 8259865
TI  - [Tumor localization of a human/mouse chimeric Fab fragment-neocarzinostatin
      conjugate].

PMID- 8259866
TI  - Management of recurrent abdominal pain.

PMID- 8259867
TI  - Adoption, genetic disease, and DNA.

PMID- 8259868
TI  - Iatrogenic deaths in hereditary fructose intolerance.

PMID- 8259869
TI  - Continuous nebulised salbutamol and oral once a day prednisolone in status
      asthmaticus.
AB  - A trial was conducted of continuous nebulised salbutamol and oral once a day
      prednisolone in a group of 11 children with status asthmaticus (group A) and
      compared with a conventional protocol comprising aminophylline infusion and
      intravenous hydrocortisone every six hours in a matched control group (group B).
      Monitoring by a clinical asthma score, pulse oximetry (oxygen saturation, SaO2),
      and peak expiratory flow rate (PEFR) revealed earlier improvement in these
      parameters in group A. Significant differences in mean SaO2 values appeared after
      12 and 18 hours respectively. Mean PEFR percentage values were higher in group A
      compared with group B. A larger number (9/11) of patients could be discharged
      from hospital within 24 hours in group A compared with group B where only 3/11
      could be discharged. All patients recovered without any side effects. It is
      concluded that continuous nebulised salbutamol and oral once a day prednisolone
      is safe and effective in treatment of children with status asthmaticus.

PMID- 8259870
TI  - Comparison of the use of Tanner and Whitehouse, NCHS, and Cambridge standards in
      infancy.
AB  - The British (Tanner and Whitehouse) and American (National Center for Health
      Statistics, NCHS) growth standards are widely used internationally, although the
      data are now over 30 years old. Routine weight data was retrieved from the child
      health records of a complete annual cohort of 3418 children aged 18-30 months to
      test the validity of these standards for modern infants. Compared with the Tanner
      and Whitehouse standards, Newcastle children rose initially and then fell a mean
      of 0.7 SDs between 6 weeks and 18 months, resulting in a threefold difference in
      the proportion of children below the 3rd centile at different ages. NCHS
      standards showed a similar pattern. When compared with modern standards from the
      Cambridge growth study, there was a much closer match, although Newcastle
      children showed a slight gain by the age of 1 year. Existing standards for weight
      introduce inaccuracy into the estimation of centile position in the early months
      of life. As both standards show similar problems this probably represents a real
      secular change due to changes in infant nutrition. These findings support the
      need to develop new national growth reference standards.

PMID- 8259871
TI  - Influence of homelessness on acute admissions to hospital.
AB  - The aim of this study was to look at the influence of homelessness on acute
      medical admissions. A prospective case-controlled study was therefore performed
      on all homeless children admitted through the accident and emergency department
      over one year, comparing them with the next age matched admission from permanent
      housing. Assessments made were: whether homelessness or other social factors
      influenced the doctors' decision to admit; differences in severity of illness;
      length of stay; and use of primary care. The admitting doctors completed a semi
      structured questionnaire during admission about social factors that influenced
      their decision to admit and graded the severity of the child's illness. The
      length of hospital stay was recorded. The family's social risk factors and
      accommodation were assessed at a home visit using a standardised questionnaire
      and by observation. Seventy homeless children were admitted. Social factors
      influenced the decision to admit in 77% of homeless children and 43% of controls.
      More of the homeless children were only mildly ill (33/70) than those from
      permanent housing (21/70), although three of the homeless children died of
      overwhelming infections compared with none of the controls. Among homeless
      families many were recent immigrants (44%). There was a marked increase in
      socioeconomic deprivation, in major life events in the previous year (median
      score 3 v 1), and in maternal depression (27% v 8%). Referral to the hospital was
      made by a general practitioner in only 5/50 (10%) of homeless compared with 18/50
      (36%) of controls. Social factors were an important influence on the decision to
      admit in over three quarters of the homeless children and resulted in admission
      when less severely ill even when compared with admissions from an inner city
      population. Even though there was marked social deprivation among the homeless
      families, the decision to admit was based on vague criteria that need to be
      further refined.

PMID- 8259872
TI  - Computed tomography with normal chest radiograph in tuberculous infection.
AB  - Children with primary tuberculosis infection without disease must be identified
      and treated preventively to avoid an increase in the incidence of tuberculosis in
      children. However, the recognition of infected cases without disease is often
      difficult. In particular, minimal active disease may be present in many cases but
      unrecognised on chest radiography. Computed tomography was therefore performed in
      15 children with tuberculous infection and a normal chest radiograph to measure
      the size of their mediastinal lymph nodes. Ten control children without
      tuberculosis were also evaluated. When compared with controls it was found that
      nine of 15 (60%) infected children had enlarged lymph nodes. Adenopathies were
      more frequent in infected children less than 4 years old than in those over 8
      years old. The demonstration of unrecognised active disease in many infected
      children raises the question of the adequate treatment for these children. It is
      proposed that a two drug regimen would be more appropriate than isoniazid alone
      in these cases.

PMID- 8259873
TI  - Malonyl coenzyme A decarboxylase deficiency.
AB  - Two new cases of malonyl coenzyme A (CoA) decarboxylase deficiency are described.
      Hitherto, the worldwide experience of the disorder has been confined to reports
      on two affected Australian children. The new cases are Scots born and are the
      offspring of consanguinous parents of Scots/Irish origin. They were investigated
      during episodes of vomiting and febrile convulsions associated with concomitant
      developmental delay. Malonic aciduria and grossly reduced malonyl CoA
      decarboxylase activity were demonstrated and the total ion current chromatograms
      of urinary organic acid profiles obtained by gas chromatography-mass spectrometry
      are presented. The clinical and biochemical features of the Scots and Australian
      patients are compared.

PMID- 8259874
TI  - Screening for a raised rectal temperature in Africa.
AB  - The main purpose of this study was to compare rectal and axillary temperature
      measurements in African children. Altogether 573 sick children were seen in an
      outpatient setting in rural West Africa. Rectal and axillary temperatures were
      measured and the parent or guardian was asked if they thought that the child had
      a raised body temperature. Normal ranges were defined from an age matched
      population of 203 healthy children. A raised axillary temperature predicted a
      raised rectal temperature with a sensitivity of 98% and a specificity of 88%. The
      parents' impression that their child had a fever was a less sensitive (89%) and
      less specific (59%) indicator of raised rectal temperature. A raised axillary
      temperature is a good screening test for a raised rectal temperature in African
      children.

PMID- 8259875
TI  - Treatment of respiratory syncytial virus infection with recombinant interferon
      alfa-2a.
AB  - A prospective randomised, double blind, controlled trial was conducted in 52
      infants to determine whether recombinant interferon alfa-2a (INF-alpha-2a) would
      reduce the morbidity of acute bronchiolitis and the respiratory syncytial virus
      shedding time. All infants had a positive direct antigen immunofluorescence test
      for respiratory syncytial virus. INF-alpha-2a (50,000 IU/kg/day) or placebo was
      administered by daily intramuscular injection for three consecutive days. Sixteen
      infants received INF-alpha-2a and 36 received placebo treatment. The two groups
      were similar in demographic characteristics and initial oxygenation. The
      treatment group, however, had a significantly higher overall score for severity
      of illness at the start of treatment. More rapid drop of the clinical score was
      observed in the INF-alpha-2a group after treatment in the first three days and
      the two groups had similar clinical severity by day 3. There was no significant
      difference of the duration of viral shedding in the two groups. In conclusion,
      the overall clinical improvement was greater in the treatment group over the
      first three days, but the duration of viral shedding was not altered.

PMID- 8259876
TI  - Resolution of hepatic abscess after interferon gamma in chronic granulomatous
      disease.
AB  - Recombinant interferon gamma has been used prophylactically in children with
      chronic granulomatous disease, but its role in the treatment of acute infective
      episodes has not been defined. A 3 year old boy presented with multiple candidal
      liver abscesses and was given intravenous antifungal treatment and he showed
      initial improvement. After six weeks his erythrocyte sedimentation rate and C
      reactive protein remained raised, and a computed tomogram showed a single abscess
      in the left lobe of the liver from which pus was drained and Staphylococcus
      aureus isolated. During the next eight months the abscess persisted despite
      appropriate intravenous antibiotics and percutaneous drainage. Subphrenic
      extension precluded definitive surgery. Nine months after initial presentation
      recombinant interferon gamma 0.05 mg/m2 intravenously was commenced three times a
      week. Complete resolution occurred within two months. It is concluded that
      interferon gamma is useful in treating infective episodes, and further study of
      the use of prophylactic antimicrobial treatment and intermittent interferon gamma
      during acute episodes is now required.

PMID- 8259877
TI  - Cystic fibrosis presenting as kwashiorkor with florid skin rash.
AB  - Two infants with a florid erythematous rash and generalised oedema,
      hypoalbuminaemia, and anaemia were found to have cystic fibrosis. This rare
      presentation is associated with false negative sweat tests, delays in diagnosis,
      and a considerable mortality. It is proposed that this presentation represents a
      manifestation of kwashiorkor secondary to malabsorption. The recognition that
      these infants have kwashiorkor provides some insight into the pathogenesis and
      management of their illness.

PMID- 8259878
TI  - Nitric oxide treatment for fulminant pulmonary hypertension.
AB  - A 3 year old child with known pulmonary haemosiderosis suffered acute circulatory
      collapse secondary to raised pulmonary vascular resistance. Nitric oxide
      inhalation produced a profound improvement in circulatory parameters and gaseous
      exchange. Nitric oxide may have a therapeutic role in acute pulmonary
      hypertensive crisis.

PMID- 8259879
TI  - Can we improve diabetes care in schools?
AB  - Results of a questionnaire study showed that parents were dissatisfied with
      school care of their children's diabetes and with teachers' knowledge of
      diabetes. Parents were more satisfied with support in school if a paediatric
      diabetes liaison service was provided rather than an adult one.

PMID- 8259880
TI  - Bovine colostrum immunoglobulin concentrate for cryptosporidiosis in AIDS.
AB  - Lactobin-R is a commercial hyperimmune bovine colostrum with potent
      anticryptosporidial activity. It was administered to a 4 year old child with AIDS
      and severe diarrhoea associated with cryptosporidiosis. There was significant
      clinical improvement in the diarrhoea and permanent elimination of the parasite
      from the gut as assessed through serial jejunal biopsy and stool specimens.

PMID- 8259882
TI  - Parental participation in case conferences: the case in favour.

PMID- 8259881
TI  - Occurrence of Duchenne dystrophy in Klinefelter's syndrome.
AB  - A boy with Duchenne muscular dystrophy and facial dysmorphism in conjunction with
      Klinefelter's genotype 47XXY is presented; this is an unusual situation with two
      genetic errors evolving over two generations. Karyotyping should be considered in
      boys with Duchenne muscular dystrophy who have unusual features.

PMID- 8259883
TI  - Parental participation in case conferences: the case against.

PMID- 8259884
TI  - Children as carers.

PMID- 8259885
TI  - Helping the young visually impaired: a view from the community.

PMID- 8259886
TI  - Crigler-Najjar syndrome type I: management with phototherapy crib mattress.

PMID- 8259887
TI  - Transient hyperphosphatasaemia of infancy and failure to thrive.

PMID- 8259888
TI  - Dual marker one day pancreolauryl test.

PMID- 8259889
TI  - Epilepsy in children and the risk of drowning.

PMID- 8259890
TI  - Injury epidemiology: emerging statistics and strategy.

PMID- 8259891
TI  - Pressure reduction of intussusception.

PMID- 8259892
TI  - A career in paediatrics? A survey of paediatric senior house officers in England
      and Wales.

PMID- 8259893
TI  - The Australian NHMRC Twin Registry: a resource for paediatric research.

PMID- 8259894
TI  - The functional independence measure: its use to identify rehabilitation needs in
      stroke survivors.
AB  - To explore the potential of the Functional Independence Measure (FIM) as a
      prognostic indicator of outcome in stroke survivors, 113 consecutive patients
      were observed from admission until discharge. Patients received assessment and
      treatment by a multidisciplinary team in a regional tertiary care stroke-specific
      rehabilitation program. The FIM, Chedoke-McMaster Stroke Assessment, and
      discharge location were used as the main outcome measures. The results suggested
      that; (1) impairment variables alone are insufficient as prognostic indicators of
      outcome; (2) the absolute admission FIM score, not the change in the FIM score,
      is the best predictor of outcome disability and place of discharge; and (3)
      subgroups of stroke survivors with differing rehabilitation needs can be
      identified. The FIM allows us to classify stroke survivors according to their
      needs; therefore, attention should be redirected to the development of prognostic
      indicators for groups of stroke survivors.

PMID- 8259895
TI  - Swallowing after unilateral stroke of the cerebral cortex.
AB  - We report differential patterns of swallowing in 40 patients with their first
      ischemic middle cerebral artery (MCA) stroke and compare these to 20 nonstroke
      controls. Stroke patients were divided a priori, into groups by right or left
      and, post hoc, primarily anterior or posterior MCA territory lesions. The left
      hemisphere subgroup was differentiated from controls by longer pharyngeal transit
      durations and from the right hemisphere group by shorter pharyngeal response
      durations. The right hemisphere subgroup was characterized by longer pharyngeal
      stage durations and higher incidences of laryngeal penetration and aspiration of
      liquid. Anterior lesion subjects demonstrated significantly longer swallowing
      durations on most variables compared to both normal and posterior lesion
      subjects. Changes in the consistency of foods and other modifications for safe
      nutrition should be considered during the first month of recovery for unilateral
      stroke patients with swallowing difficulty.

PMID- 8259896
TI  - Electromyographic biofeedback for neuromuscular reeducation in the hemiplegic
      stroke patient: a meta-analysis.
AB  - The efficacy of electromyographic biofeedback (EMG-BF) for neuromuscular
      reeducation in the stroke patient has been difficult to establish. The purpose of
      this study was to assess EMG-BF efficacy through meta-analysis. We searched the
      English-language clinical studies of biofeedback, stroke, and cerebral vascular
      disease between 1966 and 1991 using MEDLINE, PsycINFO, REHABDATA, and
      Dissertation Abstracts International. Studies were included in the analysis if
      (1) the patients sustained a cerebral vascular accident that resulted in
      hemiplegia, (2) the study had a randomized or matched control group, (3) the
      study measured a functional outcome, and (4) EMG-BF was the independent variable.
      Eight studies met the inclusion criteria (n = 192). Their average effect size was
      0.81. The 95% confidence interval for the effect size was 0.5 to 1.12. These
      results indicate that EMG-BF is an effective tool for neuromuscular reeducation
      in the hemiplegic stroke patient.

PMID- 8259897
TI  - Psychometric characteristics of a brief measure of pain-related functional
      impairment.
AB  - This study presents reliability and validity data from two samples (pain clinic
      vs medical clinic) on a five-item self-report scale, termed the Functional
      Interference Estimate (FIE), designed to measure functional impairment associated
      with chronic pain. Results from the pain clinic sample demonstrated that the FIE
      is internally consistent and has satisfactory levels of test-retest reliability,
      item-total score correlations, and convergent validity. Results from the medical
      clinic sample demonstrated that the FIE discriminated between medical clinic
      patients without pain and both medical clinic patients with pain and pain clinic
      patients. The data support the use of the FIE as one of several available
      assessment methods for evaluation of pain-related functional impairment.

PMID- 8259898
TI  - Neuropsychological function in peripheral vascular disease amputee patients.
AB  - Approximately 75% of major lower-extremity amputations are the result of
      peripheral vascular disease (PVD). Factors that predispose a patient to PVD
      (smoking, hyperlipidemia, diabetes mellitus) are also risk factors for the
      development of cerebrovascular disease, which could adversely affect
      rehabilitation. The purpose of this study was to test the hypothesis that
      cognitive deficits are present in amputee patients with PVD. Fourteen patients
      with lower-extremity amputations secondary to PVD (4 women, 10 men; mean age =
      67.4 years) were recruited from a tertiary-care center for physical
      rehabilitation. Fourteen community-dwelling healthy volunteers (9 women, 5 men;
      mean age = 69.9 years) served as age-matched and education-matched controls. To
      assess a broad range of cognitive function, we administered standard
      neuropsychological tests of memory and learning, language, praxis, visuospatial
      skills, and abstract reasoning. PVD patients performed significantly more poorly
      on certain measures of psychomotor speed (Wechsler Adult Intelligence Scale
      Revised Digit Symbol subtest) and problem solving/abstract reasoning (Modified
      Card Sorting Test) relative to controls (using the Bonferroni correction for
      multiple comparisons, p < .002). There were trends toward poorer patient
      performance on certain measures of oral fluency, concentration, reasoning, and
      visuoperceptual organization and constructional skills (p < .01). We propose that
      these cognitive deficits may be the result of unrecognized concomitant
      cerebrovascular disease in PVD patients and are part of a generalized pattern of
      vascular disease. Future research should control affective factors such as stress
      or depression surrounding amputation and attempt to identify the etiologic or
      demographic factors that are associated with neuropsychological deficits in
      patients with PVD.

PMID- 8259899
TI  - Muscle strength differences in urban and rural populations in Sweden.
AB  - The isometric extension and flexion strength of the right knee was investigated
      in 396 men and 537 women. The probands were randomly selected from the National
      Population Records, either from the city of Malmo, Sweden, or from a typical
      agricultural region 60km outside the city. Both the extension and the flexion
      strength decreased with age in both groups. Between 50 years and 80 years of age
      the decrease was almost 40%. The urban probands had significantly lower muscle
      strength in both sexes. The difference was most pronounced for the knee extension
      strength. Also, the flexion strength was less in the urban population, the
      difference significant only in octogenarians.

PMID- 8259900
TI  - Effects of a quantitative progressive rehabilitation program applied unilaterally
      to the osteoarthritic knee.
AB  - Decreases in muscular strength, endurance, and angular velocity have previously
      been demonstrated in the elderly. Osteoarthritis (OA), especially of the knee,
      may cause further reductions in these parameters and lead to functional
      limitations. This study measured the effects of a quantitative progressive
      exercise muscle rehabilitation program (QPE) that was added to a physical therapy
      (PT) program. Forty subjects (20 men and 20 women) with OA of the knees were
      randomly selected from a group of volunteers (N = 437) for the 3-month program.
      Measurements of strength, endurance, angular velocity, and the Jette Functional
      Status Index were determined before and after 1, 2, and 3 months of the program.
      The QPE program was composed of isometric, isotonic, isotonic with resistance,
      endurance, and speed contractions prescribed in a progressive sequence. Muscle
      strength (14% and 29%) and endurance (38% and 43%) increased significantly (p <
      0.05, ANOVA for repeated measures) for both the quadriceps and hamstrings,
      respectively, after rehabilitation. There were marked decreases in walking time
      and the difficulty and pain experienced during functional activities.

PMID- 8259901
TI  - Reliability of eccentric isokinetic knee flexion and extension measurements.
AB  - This study assessed the test-retest reliability of knee isokinetic eccentric
      muscle performance in subjects with and without a history of tibio-femoral
      pathology. Nineteen adults were tested at 60 degrees/sec and 180 degrees/sec on
      three occasions using a standardized protocol that incorporates a same-session
      learning phase. Results revealed moderate to excellent reliability for average
      peak torque test-retest ICC (2,1) = .58 to .96, total work ICC = .63 to .93, and
      power ICC = .67 to .93. Joint angle at peak torque was unreliable (ICC = .01 to
      .69) for both muscle groups at both angular velocities. Knee flexion reliability
      was higher than extension reliability at both 60 degrees/sec and 180 degrees/sec.
      Subjects with tibio-femoral pathologies had ICC values lower than the healthy
      subjects. Reliable eccentric isokinetic measurements can be obtained for average
      peak torque, total work, and power. Clinicians should not assume the same degree
      of reliability in testing patients as in testing healthy subjects.

PMID- 8259902
TI  - Biomechanical analysis of the knee extension exercise.
AB  - A mathematical analysis of knee extension and flexion exercise is presented to
      determine effectiveness in strengthening the quadriceps and hamstring muscles. A
      quantitative relationship between the quadriceps force and the hamstring force is
      obtained for several variations of the exercises. The theoretical results are
      supplemented with experimental studies performed on subjects exercising with the
      Tekdyne Incentive Dynamometer.

PMID- 8259903
TI  - How do physiological components of balance affect mobility in elderly men?
AB  - The purpose of this study was to assess the relationship between physiological
      components of balance and mobility in elderly men without significant disease.
      Our a priori hypothesis was that physical function is influenced more by
      accumulated modest impairments than by a single deficit. We examined 39
      ambulatory men (> 69 years). Subjects were classified functionally as high,
      intermediate, or low. Assessment included mobility functions (6-minute walk,
      mobility skills, reach, 10ft walk time) and physiological components of balance:
      sensory (vibration, proprioception, vision, vestibular), effector (ankle, knee,
      hip strength, range of motion), and central processing (response time to
      perturbations). All mobility functions were significantly (p < .05) different
      between groups. Impairments in components of postural control were rarely
      different between groups: the major differences were in ankle strength and visual
      fields. The number of impaired domains differed across the three groups. Nineteen
      percent of the low group had at least three domains impaired; none of the
      intermediate or high groups were impaired in three domains. Fifty-six percent of
      the low, 20% of the intermediate, and 7% of the high were impaired in two or more
      domains. Variability in specific mobility measures was also predicted by the
      number of impaired domains. The decline in physical function may be better
      explained by the accumulation of deficits across multiple domains than by any
      single specific impairment.

PMID- 8259904
TI  - Prediction of deficits in behavioral self-regulation among persons with multiple
      sclerosis.
AB  - There is evidence that the lesions characteristic of multiple sclerosis (MS) may
      isolate prefrontal cortex from other regions of the brain. These findings are
      consistent with neuropsychological data that show many persons with MS to perform
      poorly on tests thought to assess the executive functions presumably mediated by
      the prefrontal area. Furthermore, prefrontal lesions have long been associated
      with the occurrence of various kinds of behavior pathology. These data prompted
      us to test the hypothesis that deficits in behavioral regulation typical of
      frontal lobe dysfunction might play a significant role in the occurrence of
      behavioral disturbances among persons with multiple sclerosis hospitalized for
      treatment with methylprednisolone and rehabilitation therapies. Twenty-three
      chronic progressive MS patients were compared with 23 healthy controls matched on
      age and education. Both groups were administered the Mini Mental State Exam
      (MMSE) and the Behavioral Dyscontrol Scale (BDS), a test based on Luria's studies
      of frontal lobe dysfunction that measures the capacity for regulation of
      purposeful activity. The MS patients performed more poorly than comparison
      subjects on the BDS, but not on the MMSE. The MS sample was then divided into two
      groups according to whether patients obtained low (n = 8) or high scores (n = 16)
      on the BDS. Compared with high-scoring patients, low-scoring patients showed
      greater behavioral inertia and greater disruption of the ability to regulate
      purposeful activity in the performance of activities of daily living. Behavioral
      disturbances in these individuals thus require careful assessment. Among those
      who show deficient capacity for behavioral control, the most efficacious
      interventions may involve the use of cueing, provision of structure, supervision,
      and environmental modifications.

PMID- 8259905
TI  - Pneumococcal vaccination for patients with spinal cord injury.
AB  - Pneumococcal vaccination is recommended for persons with increased risk for
      pneumococcal disease or its complications. Even though recommendations for
      pneumococcal vaccination of the spinal cord injury (SCI) population have not been
      made to date, many SCI patients may qualify for vaccination. The purpose of this
      study was to examine the antibody response of SCI patients to polyvalent
      pneumococcal vaccine. Immunoglobulin G antibodies to five commonly infecting
      pneumococcal capsular polysaccharides were determined in 40 SCI patients and in
      an age-matched control of 40 able-bodied persons before and 4 to 6 weeks after
      vaccination. There were no significant differences in the mean antibody levels
      and the percentage of persons who responded to the five capsular polysaccharides
      in the SCI versus control groups. Among SCI patients, the antibody response was
      generally not affected by age, time since injury, or level of lesion. The
      antibody response to pneumococcal vaccination in SCI patients seems adequate.

PMID- 8259906
TI  - Sensate and insensate in-shoe plantar pressures.
AB  - In the individual with loss of protective sensation, the presence of high plantar
      pressures has been considered a risk factor for the development of plantar
      ulceration. Previous studies of insensate plantar pressures have measured a
      limited number of isolated, barefoot steps in a laboratory setting. Such isolated
      snapshots of barefoot plantar pressures do not give us insight into possible step
      to-step variations or what plantar pressures occur when wearing shoes. The
      purpose of this study was to quantitatively examine and compare in-shoe plantar
      pressures during continuous walking by normal sensate and diabetic insensate
      subjects. A portable, insole data-acquisition system was used for pressure
      measurement during 4 minutes of normal continuous walking. Seven pressure sensors
      were placed in each insole under posterior and anterior heels, the metatarsal
      heads, and hallux. Twelve sensate and five insensate subjects were studied. We
      found that the insensate group had higher plantar pressures under posterior and
      anterior heels and the first metatarsals compared with the sensate group. From
      the study of the coefficients of variation, we demonstrated a larger step-to-step
      variation in plantar pressures for the insensate during continuous walking,
      suggesting the need for caution in interpreting the data from isolated force
      plate steps when studying insensate individuals.

PMID- 8259907
TI  - Comparison of gait between young adults fitted with the space foot and
      nondisabled persons.
AB  - Prosthetic feet having new keel configurations were specially designed to store
      deformation energy during early and midstance and release it at push-off. These
      prosthetic components display longitudinal symmetry favoring good energy
      storage/release capability in the sagittal plane. The need for inverters/everters
      either as independent components or within the foot structure has long been
      recognized. This article documents the walking and slow jogging performances of
      six young adults wearing below-knee prostheses fitted with the Space Foot, a
      flexible foot prosthesis that provides medio-lateral control at heel-strike and
      lateral and forward propulsion at push-off. Results indicate that the Space Foot
      behaves as a flexible keel foot prosthesis. Its gait performances are also good
      for fast walking; however, the Space Foot's actual design should be modified if
      used in sporting activities involving running.

PMID- 8259908
TI  - Women's health: new frontiers in rehabilitation medicine.

PMID- 8259909
TI  - The modified Le Fort III osteotomy in the correction of mid-facial deficiency.
      Case reports.
AB  - Maxillary hypoplasia is a common diagnosis in the spectrum of dentofacial
      deformities and is usually corrected by a Le Fort I maxillary advancement
      osteotomy. The modified Le Fort III osteotomy enables correction of mid-face
      hypoplasia where the maxillary hypoplasia is associated with infraorbital and
      zygomatic deficiency. This procedure is described and illustrated in two case
      reports. It is considered to be a superior technique to the maxillary osteotomy
      and onlay procedure and is recommended for use in selected patients.

PMID- 8259910
TI  - Failure of an intra-oral wound to heal. Case report.
AB  - Failure to treat the soft tissue component of dento-alveolar wounds may
      complicate wound healing mechanisms, retarding the rate of healing and increasing
      the risk of infection. A case is presented of a five-year-old with an intra-oral
      wound which, left untreated for eleven days, failed to resolve.

PMID- 8259911
TI  - Some problems of dental treatment. Part 1. Patient anxiety: some correlates and
      sex differences.
AB  - An analysis of questionnaire data obtained from 110 adult patients attending the
      Dental Department of the Lower Hutt Hospital and four private dental practices in
      Lower Hutt and Wellington, New Zealand indicates that patient treatment anxiety
      is more severe in women than men and that it is correlated with patients'
      descriptions of dental treatment. Altogether, survey findings indicate that
      treatment anxiety has adverse effects and that, with few exceptions, it results
      directly or indirectly from unpleasant experiences during dental treatment. Two
      of the most common of such experiences are evidently pain arising from the
      stimulation of sensitive tissue and oral injections. The eradication of treatment
      anxiety is therefore heavily dependent on the unobtrusive induction of profound
      analgesia prior to painful procedures.

PMID- 8259912
TI  - Cost-conservative dentistry: appropriate dentistry at lower cost.
AB  - Dental practitioners in both private and public dentistry are faced with patients
      who for reasons of public or private finance are not able to be treated with the
      most sophisticated available dentistry. A concept of appropriate dentistry is
      provided whereby, with reference to available literature, it is shown that cost
      conservative treatment can be provided that is likely to be satisfactory to both
      the client and the practitioner.

PMID- 8259913
TI  - Orthodontic treatment needs in Westmead Hospital Dental Clinical School.
AB  - One hundred and fifty-four adolescents, 76 female and 78 male consented to take
      part in this survey. The two authors examined and assessed them for dental
      aesthetics, malocclusion related features and TMJ related signs. The patients
      were also questioned about their opinion of dental aesthetics, their interest in
      having orthodontic treatment and their TMJ symptoms. Only 63 per cent of the
      adolescents who were considered suitable for orthodontic treatment expressed an
      interest in wanting treatment. Twenty-seven per cent of patients had signs and/or
      symptoms of TMJ disturbance. No association was found between individual
      malocclusion problems and TMJ signs and symptoms. The authors considered 56.5 per
      cent of the total group for orthodontic treatment, the majority for aesthetic
      reasons, and placed them into high, medium and low priority groups. Fixed
      appliance therapy for both arches was the recommended type of treatment for most
      patients.

PMID- 8259914
TI  - Oral health status and treatment needs of non-institutionalized persons aged 60+
      in Adelaide, South Australia.
AB  - There has been a growing recognition of the need to obtain information about the
      oral health of older Australians. The aim of this report is to provide
      descriptive epidemiological information about the oral health and treatment needs
      of non-institutionalized older adults in Adelaide. Data from interviews with 178
      persons aged 60+ were obtained from a pilot study. Clinical data were available
      for 106 persons who participated in oral examinations. Among the 52.9 per cent of
      dentate persons, the prevalence of root decay (27.1 per cent) was slightly higher
      than coronal decay (23.6 per cent). Some 28.1 per cent of dentate persons had a
      serious periodontal condition, defined as the presence of four or more teeth with
      at least 5 mm or more of periodontal attachment loss and periodontal pocketing of
      4 mm or more at one or more of those teeth. The majority of persons (83.8 per
      cent) wore one or two dentures. Disorders associated with dentures were frequent,
      affecting 77.4 per cent of upper denture wearers and 72.5 per cent of lower
      denture wearers. Persons who were older, who had lower educational attainment or
      lower household incomes were disadvantaged in aspects of oral health status and
      dental caries. However, there were no consistent associations between chronic
      medical conditions and oral disorders. Despite the high prevalence of oral
      impairment, reflecting extensive disease activity in the past, high levels of
      untreated disease were relatively uncommon. Instead, a high prevalence of oral
      disorders created a substantial need for basic forms of dental treatment in this
      group.

PMID- 8259915
TI  - Relationship between CPITN and oral health behaviour in Japanese adults.
AB  - Many studies on toothbrushing have concentrated on clinically diagnosing plaque
      and measuring periodontal status as indicators of oral health behaviour. From a
      behavioural point of view, however, the more important objective is the health
      behaviour itself. To investigate the relationship of oral health behaviour to
      periodontal status, 517 urban employees in Japan (249 men and 268 women aged 20
      59 years) responded to a 20-item dental health behaviour questionnaire, entitled
      the HU-DBI, and had their periodontal conditions examined using the CPITN. Only 1
      per cent were found with a healthy periodontium (Code 0), and 9 per cent had
      bleeding on probing (Code 1). Calculus (Code 2) was the most prevalent condition
      with 51 per cent of subjects having this code as the worst condition, followed by
      shallow pockets (Code 3) in 30 per cent, and deep pockets (Code 4) in 9 per cent
      of the sample. The mean HU-DBI score was 4.2 (out of 12). Females had somewhat
      higher scores than males (4.4 vs. 4.0, p < 0.05). CPITN had a negative
      relationship with the HU-DBI (r = -0.26, p < 0.001), and a positive relationship
      with age (r = 0.40, p < 0.001). Similar relationships were observed in each
      gender. These data demonstrate the relationship of age with periodontal status,
      and periodontal status with oral health behaviour. A two-dimensional matrix of HU
      DBI score by CPITN may provide a simple and effective means of identifying low
      and high risk individuals.

PMID- 8259916
TI  - The evolution of the complete denture base. Theories of complete denture
      retention--a review. Part 3.
AB  - The history of denture base materials and the accompanying development of
      impression techniques are traced from the earliest times to the present day (Part
      1) as a prelude to a study (Part 2-4) of the various theories that have been
      advanced to explain retention of the base without mechanical support. These
      theories are critically reviewed and tabulated in chronological order. Some areas
      for further investigation are identified.

PMID- 8259917
TI  - A simple eyesight screening programme for dental undergraduates: results after 7
      years.
AB  - This paper reports the results of a simple eyesight screening programme for
      dental undergraduates which has been used for 7 years. Examinations were
      performed by orthoptists at a general hospital associated with the dental school.
      Defects in visual acuity, squints, limitations of convergence, defective
      stereopsis and colour vision were found. Many students were unaware of their
      visual defects, and the findings support the continued use of visual screening to
      identify and encourage those with defects to seek professional treatment at an
      early opportunity. Many of the defects were correctable or could be improved with
      help. Those with defective colour-vision were encouraged to seek assistance with
      shade selection during their clinical careers. The value of visual screening and
      the significance of the findings are discussed.

PMID- 8259918
TI  - A microcomputer system for physiological data collection and analysis.
AB  - The ability to monitor and record activity within the masticatory system is of
      importance to both general practitioner and research worker. Recent developments
      in physiological data collection and analysis at the Department of Anatomy,
      University of Queensland, have achieved that objective in a simple and cost
      effective manner. Recording, printing, plotting, and a wide range of analysis
      procedures can be undertaken utilizing relatively inexpensive available
      computers.

PMID- 8259919
TI  - Prophylaxis for the prevention of infective endocarditis.

PMID- 8259920
TI  - Antibiotic prophylaxis and endocarditis.

PMID- 8259921
TI  - Terminology of facial morphology in the vertical dimension.

PMID- 8259922
TI  - The subperiosteal implant.

PMID- 8259923
TI  - Altered nucleosome spacing associated with Down syndrome.
AB  - Micrococcal nuclease digestions of human leukocytes were analyzed using gel
      electrophoresis. The relative size (or average number of nucleotides) of
      nucleosomes was determined. The mean nucleosome size of the normal 46 chromosome
      karyotype is 185 +/- 2 bp. There was no significant variation in nucleosome size
      within the normal population due to age, sex, or race. The mean nucleosome size
      of the Down syndrome samples is 173 +/- 3 bp. These two groups have separate
      normal distribution curves which do not overlap and are significantly different
      at P < 0.1%.

PMID- 8259924
TI  - Linkage between complement components 6 and 7 and glutamic pyruvate transaminase
      in the marsupial Monodelphis domestica.
AB  - The sixth and seventh components of complement were found to be polymorphic and
      tightly linked in the laboratory opossum (Monodelphis domestica), as they are in
      eutherian mammals. In addition, strong evidence for linkage of the C6-C7
      haplotype to the gene for glutamic pyruvate transaminase (GPT) was obtained for
      females but not for males. This result, combined with previous observations,
      established as a generality that recombination is severely reduced in females of
      this species by comparison with males. It also establishes synteny of C6-C7 and
      GPT in a marsupial species, as exists in mice. Because these loci are not
      syntenic in humans, the results imply that this synteny is ancestral to the
      separation of marsupials and eutherians and that it was broken relatively
      recently in the mammalian lineage leading to human beings. The newly described C6
      and C7 polymorphisms provide additional power for developing a linkage map for M.
      domestica and for localizing genes that confer susceptibility to diseases for
      which this species is used as a model.

PMID- 8259925
TI  - Genetic studies of water buffalo blood markers. I. Red cell acid phosphatase,
      albumin, catalase, red cell alpha-esterase-3, group-specific component, and
      protease inhibitor.
AB  - We have developed the methodologies for typing and family studies to establish
      the modes of inheritance of water buffalo red cell acid phosphatase (Acp),
      protease inhibitor (Pi), and group-specific component (Gc) on isoelectric
      focusing and albumin (Alb), red cell alpha-esterase-3 (Est-3), and catalase (Cat)
      on polyacrylamide gel electrophoresis. Family studies showed that Pi, Gc, Alb,
      and Cat are coded by autosomal genes with two codominant alleles, while Est-3 is
      autosomal with two codominant alleles and a recessive null allele and Acp
      exhibits three codominant alleles.

PMID- 8259926
TI  - Allozyme variation in stable flies (Diptera: Muscidae).
AB  - Polyacrylamide gel electrophoresis was used to resolve allozymes in the
      cosmopolitan blood-feeding stable fly, Stomoxys calcitrans (L.). Nineteen of 38
      loci were polymorphic (53%). Mean heterozygosities among all loci and among only
      polymorphic loci were 0.096 and 0.182, respectively. These gene diversity
      measures are about half those among other muscid Diptera. Variation in gene
      frequencies was examined in 10 natural stable fly populations from Iowa and
      Minnesota. Gene frequencies were homogeneous at five of eight loci among six
      populations in 1990 and eight of eight loci among four populations in 1992.
      Wright's F statistics showed no significant departure from random mating among
      stable flies. It was concluded that gene flow compensates for any local
      differentiation in stable fly populations.

PMID- 8259927
TI  - Nucleotide sequence and molecular evolution of the gene coding for glyceraldehyde
      3-phosphate dehydrogenase in the thermoacidophilic archaebacterium Sulfolobus
      solfataricus.
AB  - A Sulfolobus solfataricus genomic library cloned in the EMBL3 phage was screened
      using as probes synthetic oligonucleotides designed from the known amino acid
      sequence of a peptide obtained from the purified glyceraldehyde-3-phosphate
      dehydrogenase (aGAPD) protein. The screening led to the isolation of six
      recombinant phages (lambda G1-lambda G6) and one of them (lambda G4) contained
      the entire GAPD gene. The deduced amino acid sequence accounts for a protein made
      of 341 amino acids and the initial methionine is encoded by a GTG triplet.
      Alignment of the S. solfataricus aGAPD sequence versus GAPD from archaea,
      eukarya, and bacteria showed that aGAPD is very similar to other archaebacterial
      but not to eukaryotic or eubacterial GAPD. For known archaebacterial GAPD
      sequences, the rate of nucleotide substitutions per site per year showed that
      these sequences are homologous not only at the amino acid but also at the
      nucleotide level. The evolutionary rates are nearly similar to those reported for
      other eukaryotic genes.

PMID- 8259929
TI  - Ergonomics. Importance to occupational health.

PMID- 8259928
TI  - Identification of an allelic variant of isoform MLC1-V/sB (human myosin light
      chain).
AB  - A study of 250 specimens of human myocardium by two-dimensional gel
      electrophoresis revealed an allelic variant of isoform MLC1-V/sB, which was
      identified by immunoblotting with monoclonal antibody against MLC1-V/sB and
      peptide mapping after in situ tryptic digestion of electroblotted proteins. The
      substitution Asn-144 for His-144 was found in this new allelic variant of MLC1
      V/sB.

PMID- 8259930
TI  - Marketing health promotion: hitting or missing the target in occupational health.
AB  - 1. Occupational health nurses can use marketing strategies to plan, offer, and
      manage health promotion programs; and to conduct research aimed at better
      understanding the health needs of workers. 2. By applying a social marketing
      orientation to health promotion planning, occupational health nurses can tailor
      programs to fit employees' needs, and deliver health messages that are readily
      understandable to worker groups. 3. A priority in implementing any occupational
      health program or service is learning about the needs, desires, and health habits
      of employees. 4. Greater benefits to employee health may occur by targeting
      change in structures and systems at the workplace rather than solely focusing on
      lifestyle issues.

PMID- 8259931
TI  - Identifying sources of disease in agriculture: a role for occupational health
      nurses.
AB  - 1. Agriculture is one of the most hazardous industries in the United States,
      vying with mining and construction as the industry with the highest work fatality
      rate. 2. Over 40% of Midwestern farm operators also work off the farm.
      Understanding the disease risks of farming can help the occupational health nurse
      provide comprehensive care to these dual workers. 3. Sources of disease in
      agriculture may be physical, chemical, biological, or psychosocial in nature. 4.
      Effective strategies in the control of agricultural hazards include engineering
      modifications, use of personal protection products, and educational efforts.

PMID- 8259932
TI  - When the injured worker retains an attorney: the relationship between attorney
      involvement and case outcome.
AB  - 1. A key to the successful rehabilitation of the injured worker is an
      understanding of the barriers to success and methods to overcome those barriers.
      2. The purpose of this study was to determine whether a relationship exists
      between attorney involvement and case outcome in the nursing management of
      industrially injured workers. 3. This study found a strong relationship between
      attorney involvement and not returning to work and also between attorney
      involvement and interrupted case management. Attorney involvement may be
      considered as a factor when evaluating the potential and/or retrospective success
      of rehabilitative efforts.

PMID- 8259933
TI  - Coping process theory: a tool to reduce stress and cardiovascular disease.
AB  - 1. Associations exist between stress and cardiovascular disease. This article
      presents the coping process theory as a possible strategy to reduce the incidence
      of cardiovascular disease. 2. The occurrence of coronary heart disease may be
      reduced by using the coping process to manage stress in the workplace. If the
      disease is present, coping with the stress of having the disorder diminishes its
      recurrence. 3. Social support is a valuable coping resource; its association with
      cardiovascular disease is demonstrated.

PMID- 8259934
TI  - Obesity in adult females: the relationship among personality characteristics,
      dieting, and weight.
AB  - 1. The author studied 225 employed women in the New York Metropolitan area
      between the ages of 25 and 55 years. The Disinhibited Dieters in this study were
      overweight, depressed, anxious, and had a low self esteem. The Cognitive
      Controlled Dieters were not depressed or anxious, had a positive self esteem, and
      were not overweight. 2. The only significant variable between successful
      Cognitive Controlled Dieters and Disinhibited Dieters was exercise. 3. Nurses
      must examine their own beliefs and feelings concerning weight and eating and the
      connection with depression, anxiety, and self esteem before they can successfully
      relate to clients. 4. Attitude, cognitive changes, involvement in sports and
      exercise, and healthy eating are primary prevention interventions to be utilized
      by the nurse.

PMID- 8259935
TI  - The National Institute of Nursing Research: a reality.

PMID- 8259936
TI  - Job stress and occupational health nursing: modeling health affirming choices.
AB  - 1. Job stress is a condition or event in the workplace that induces strain (a
      physical, psychological, or behavioral response to a stressor). The outcome of
      unrelieved job stress can be burnout. 2. Occupational health nurses can
      experience job stress in the areas of intrinsic job factors, organizational
      structures, reward systems, human resource systems, and leadership. 3. Stress
      reduction techniques can be grouped into physical, social, spiritual,
      intellectual, emotional, and environmental strategies. 4. Application of stress
      reduction strategies to reduce experienced job stress in occupational health
      nurses is one way occupational health nurses can model health affirming choices.

PMID- 8259937
TI  - On the job conflict: how to survive.
AB  - 1. Conflicts arise when deep seated but diametrically opposed views clash. 2.
      Handling on the job conflict well requires a process of emotional and
      intellectual fine tuning that can, eventually, lead to a workable solution. 3. A
      Series of identifiable steps are experienced in working through value conflicts.
      4. Conflict can be a growth experience, expanding professional confidence and
      adding to personal stature by keeping ideals intact.

PMID- 8259938
TI  - Occupational exposure to bloodborne diseases and universal precautions:
      measurement of health care workers' self reported attitudes.
AB  - 1. As the numbers of persons infected with bloodborne diseases continues to
      increase, it is paramount that all health care workers exhibit behaviors
      reflecting unerring compliance with universal precautions. 2. Physicians and RNs
      who are highly trained in bloodborne diseases and universal precautions, who have
      the tools available for universal precautions, and who are exposed to people with
      bloodborne diseases, are overwhelmingly not complying with universal precautions.
      3. To better understand how attitudes impact behaviors, a valid and reliable tool
      was developed which measured health care workers' attitudes toward bloodborne
      diseases and universal precautions. 4. Training programs addressing attitudes and
      knowledge may help change health care workers' non-compliant behaviors into
      behaviors reflecting compliance with universal precautions.

PMID- 8259939
TI  - Working mothers and infant care: a review of the literature.
AB  - 1. The number of women who returned to work after childbirth increased steadily
      through the 1980s, with many mothers returning to work earlier than ever before.
      This trend has caused new mothers, their employers, and legislators to examine
      the issue of infant day care. 2. Infant day care availability, arrangements, and
      cost influence maternal work force participation. These concerns may also impact
      on the physical and mental health of the working mother. 3. Further research is
      needed to determine if and how infant day care concerns affect worker
      productivity, and to determine how to obtain quality day care at a reasonable
      cost.

PMID- 8259940
TI  - Radon: its impact on the community and the role of the nurse.
AB  - 1. Radon contamination is of growing concern in many industries and communities,
      but it need not remain a hazard. Testing can be inexpensive and mitigation may be
      as simple as opening a window. 2. High risk areas are known. For more information
      on radon one may contact the local EPA office. The address is found in the
      government section of the white pages of the telephone directory. 3. Occupational
      health nurses are uniquely positioned to gather and disseminate much needed
      information on the effects of radon.

PMID- 8259941
TI  - The Family & Medical Leave Act of 1993.

PMID- 8259942
TI  - Agricultural health and safety.

PMID- 8259943
TI  - Health and safety hazards associated with farming.
AB  - 1. Farming is a dangerous occupation with many potential physical, chemical, and
      biological hazards. Hazards include noise, machinery, motor vehicles,
      electricity, temperature extremes, pressurized hydraulic fluids, grain storage
      facilities, hand and power tools, repetitive motion, vibration, chemicals, dusts,
      gases, and infectious agents. 2. Psychosocial factors related to agriculture
      include stress, economic considerations, poor access to health care, and injuries
      to minors who begin working at a young age. 3. Many who farm also work at other
      jobs. Farm related illnesses and injuries can be costly to non-farm employers in
      terms of lost work time, medical insurance, and life insurance. 4. Occupational
      health nurses can promote agricultural occupational health through companies that
      employ farmers and through community organizations, thereby contributing to a
      better understanding of farm related hazards and developing strategies for
      reducing these hazards.

PMID- 8259944
TI  - The Occupational Health Nurses in Agricultural Communities program: identifying
      and preventing agriculturally related illnesses and injuries.
AB  - 1. The Occupational Health Nurses in Agricultural Communities (OHNAC) program is
      a national surveillance program to identify and prevent agriculturally related
      illnesses and injuries. Locally based nurses work closely with health
      departments, hospitals, physicians, and other providers to identify and report
      sentinel health events. 2. Through OHNAC, sentinel health events are assessed and
      evaluated to identify occupational risk factors that may be applicable to the
      larger community of agricultural workers. This information is then disseminated
      nationally, locally, and to the individual workers. 3. The surveillance and
      investigation information is used to develop programs to prevent agricultural
      illnesses and injuries. The use of case based surveillance and subsequent data
      driven interventions has broad applicability for occupational health nurses in
      other industrial sectors.

PMID- 8259945
TI  - The role of the agricultural health nurse: bringing together community and
      occupational health.
AB  - 1. Agricultural work is one of the most hazardous occupations in the United
      States. However, an occupational safety and health agenda for agriculture is
      lacking. 2. The agricultural health nurse draws on knowledge of community health
      and occupational health nursing to meet the needs of the farm work force. 3. The
      agricultural health nurse uses creative approaches to gather data about the farm
      work force and the work environment. 4. Community based strategies, such as
      coalition building, are important to develop programs that address agricultural
      safety and health problems.

PMID- 8259946
TI  - Agricultural injury surveillance: occupational health nurse's role.
AB  - 1. Iowa farmers die from work related injuries at a rate of two to three times
      the rate of manufacturing workers. Farming ranks second highest in occupational
      fatalities in Iowa. 2. While all deaths involved multiple causal factors, the
      tractor was the most frequent agent of injury causing death. 3. In Iowa, 89% of
      agriculture related deaths occur in males. 4. Iowa was the first state to require
      statewide reporting of agriculture related injuries for the purpose of planning
      interventions.

PMID- 8259947
TI  - Scalping accidents with shielded PTO units: four case reports.
AB  - 1. The type of guard on a hay baler, noted as the inverted U-shield, does not
      completely enclose the driveline. The underneath side is extremely hazardous, and
      entanglement is likely. 2. Wind speed and direction, height of the driveline, and
      workers' hair length may contribute to the risk for entanglement. 3. This type of
      driveline warrants retrofitting and recognition of the need to shut off the
      driveline before approaching it. 4. Operators should periodically examine
      machinery to determine whether unguarded areas on the machine pose a hazard, and
      contact an authorized equipment dealer to determine if any of their machinery
      requires a retrofit shield or other safety modification recommended by the
      manufacturer.

PMID- 8259948
TI  - Building coalitions: a community wide approach for promoting farming health and
      safety.
AB  - 1. The context of agriculture in the Midwest, given many smaller, family run
      operations, presents multiple and complex challenges; occupational health
      intervention strategies used in other industries are not immediately applicable.
      2. Public health nurses in Minnesota's Occupational Health Nurses in Agricultural
      Communities project (OHNAC) are applying the strategies of community wide health
      promotion through community organizing for farm health and safety promotion. 3.
      The theoretical basis for community wide health promotion encompasses theory from
      several disciplines, and a five stage model for community organization in health
      promotion has been developed and tested. 4. At the root of tis approach to farm
      safety is the effort to change long held beliefs and community norms, especially
      the belief that farm injuries and fatalities are a necessary part of agricultural
      work.

PMID- 8259949
TI  - Low back pain.

PMID- 8259950
TI  - Continuous Quality Improvement in occupational health nursing.

PMID- 8259951
TI  - [Teaching in blood transfusion: from the education requirement to accreditation].

PMID- 8259952
TI  - [HIV infection among type A and B hemophiliacs].
AB  - Evolution of HIV infection was studied in 480 hemophiliacs A and 78 hemophiliacs
      B treated in the "Centre-West" Region. 23.3% hemophiliacs A and 46.1%
      hemophiliacs B were contaminated by HIV. In this region, HIV seroprevalence in
      hemophiliacs A was lower than the prevalence noted at the national level (51.2%);
      this is certainly due to the use of frozen cryoprecipitates in the treatment of a
      high number of hemophiliacs A. A higher number of hemophiliacs B developed the
      disease: 12.5% hemophiliacs A versus 22% hemophiliacs B. Moreover hemophilic B
      patients had a more rapid evolution towards the disease since 6 out of 14
      hemophiliacs A and 7 out of 8 hemophiliacs B with AIDS died. The fact that
      hemophiliacs B were significantly older than hemophiliacs A might be one of the
      reasons, but it must be noted that the contamination often occurred earlier in
      hemophiliacs B and was perhaps more important. The more severe evolution in the
      hemophiliac B group noted in our region is not found in American studies, which
      may be due to the different ways of preparing Factor IX concentrates in France
      and the United States.

PMID- 8259954
TI  - Teaching scientific integrity and the responsible conduct of research.
AB  - Since 1990, federal guidelines have required "instruction about the responsible
      conduct of research" for science trainees who are supported by certain National
      Research Service Award (NRSA) training grants. This article reports how one
      school, The University of Chicago, responded to this requirement by developing a
      two-year "scientific integrity" program, targeted for but not limited to trainees
      on NRSA grants. The program features lectures the first year and seminars the
      next on a variety of topics related to the responsible conduct of research. This
      arrangement allows trainees to benefit both from the presentations of important
      university and outside speakers and from the intimate exchange possible only in
      smaller group settings. The program is an ongoing course rather than an intensive
      one- or two-day effort, and is intended not as an effort to reform dishonest
      persons who are likely to commit outright fraud but to serve the large group of
      honest trainees by helping them learn the important ethical issues and norms in
      the practice of good science, recognize areas of ethical conflict in research and
      scientific training, and understand their own values better. The authors discuss
      some major structural, procedural, and philosophical questions that had to be
      faced as the program was developed. They report the difficulties of evaluating
      such a program but believe that it and programs like it can have a variety of
      benefits, which they describe, for both the trainees themselves and the larger
      research community.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8259953
TI  - [Influence of clinical status on the efficacy of stored platelet transfusion].
AB  - The efficiency of stored platelet transfusion was evaluated in terms of clinical
      status in 136 thrombocytopenic patients. In a paired prospective study in which
      fresh platelets were used as controls, clinical efficiency was assessed on the
      basis of the ability to increase platelet count (recovery) and the interval to
      the next transfusion (D). In 48 clinically stable patients, recovery of fresh and
      stored platelets was similar (47% and 41% respectively) and the interval to the
      next transfusion was D4 and D3. In contrast, 27 patients who had bacterial
      infections showed significantly different recoveries (24%/5%) and the interval to
      the next transfusion was D3/D1 for fresh and stored platelets respectively.
      Similarly, in 16 patients who were treated concurrently with Amphotericin B, 18
      other patients with graft-versus-host disease, 5 with splenomegaly and 3 with
      veno-occlusive disease (VOD), fresh platelets performed better than stored
      platelets, showing recoveries of 27%/18%, 29%/15%, 15%/1%, 22%/3%. Furthermore,
      the need for retransfusion within 24 hours was significantly increased with
      stored platelets. In 19 patients with anti-HLA allo-immunization who were
      transfused with HLA-matched fresh and stored APC, efficiency was similar (38%/36%
      and D4/D3). This study indicates that the storage has a major detrimental effect
      on platelet recovery and survival in patients with certain clinical conditions.

PMID- 8259955
TI  - Creating a course on ethics in the biological sciences.
AB  - The authors examine the social and scientific context within which a course on
      the ethical dimensions of the biological sciences was created in the mid-1980s to
      instruct students at The University of Texas-Houston Health Science Center's
      Graduate School of Biomedical Sciences. They discuss how the basic purposes of
      such a course--to help students resolve ethical issues encountered in the
      scientific work, examine the values underlying science, and explore its relation
      and obligations to society--may be accomplished, and describe the salience to
      scientific work of two ethical values significant for science, truthfulness and
      benefit to others, to demonstrate the application of ethics to science. The
      present version of the course is described. Particular issues arising in the
      construction of a course on ethics and science are described, such as gaining
      faculty support, selecting instructors, constructing a syllabus of topics, using
      cases in instruction, creating examinations dealing with students from other
      cultures who may have difficulty with applying and using American values, and
      evaluating the educational effort.

PMID- 8259957
TI  - Medical student academic misconduct: implications of recent case law and possible
      institutional responses.
AB  - Recent case law has protected medical students found guilty of academic
      misconduct from severe sanctions by emphasizing due process and contractural
      rights. In light of this development, proactive approaches should be considered
      by medical schools. Faculty or administrators who have legal backgrounds are more
      likely to avoid breach of contract and violation of due process and should be
      appointed as hearing officers in cases of alleged academic misconduct. Finally,
      determination of a student's mental state (as defined in the MPC) by the hearing
      officer is a fair and rational method of determining what sanctions should be
      placed on medical students found to have cheated or plagiarized.

PMID- 8259956
TI  - Graduate teaching in principles of scientific integrity.
AB  - Training in the responsible conduct of research in the biomedical sciences is on
      its way to being a standard component in the graduate biomedical curriculum.
      Emphasis in this area has been catalyzed by certain requirements for such
      training imposed by the National Institutes of Health and by an increased
      awareness of relevant issues created by the publicity and discussion of incidents
      of scientific misconduct. The authors describe the development and formalization
      of a course about the responsible conduct of science for students in the
      biomedical disciplines at Virginia Commonwealth University. In addition, they
      discuss general considerations of course content important in teaching scientific
      integrity; examine the use of published resource materials and documents from
      professional societies, institutions, states, and the federal government as
      teaching tools; and describe the importance of case studies as vehicles for
      teaching scientific integrity.

PMID- 8259958
TI  - Health care workforce reforms: meeting primary care needs.

PMID- 8259959
TI  - What medical schools must first do if they want to serve their communities.

PMID- 8259960
TI  - Residency rotations to foster careers in rural health care.

PMID- 8259962
TI  - Disagreements between students and preceptors in assessing students' interest in
      primary care.

PMID- 8259961
TI  - Using elderly disabled patients to teach history taking and physical examination.

PMID- 8259963
TI  - Using role models to increase students' interest in primary care.

PMID- 8259964
TI  - Characteristics of dean's letters in 1981 and 1992.
AB  - PURPOSE: To compare results from 1981 and 1992 national surveys of the writers of
      medical school dean's letters, and to rate the 1992 letters based on the
      guidelines recommended by the Association of American Medical Colleges (AAMC).
      METHOD: In early 1992 a survey was administered to the dean's letter writers at
      all 125 U.S. medical schools with fully accredited four-year programs; the survey
      incorporated many items from a 1981 survey. In addition, 550 dean's letters from
      all U.S. medical schools for the graduating class of 1992 were collected and
      rated based on guidelines published by the AAMC in 1989. RESULTS: The response
      rate of the 1992 survey was comparable to that of the 1981 survey (85% and 87%,
      respectively). In both surveys, slightly more than half the schools used more
      than one letter writer; however, the 1992 letters were longer and there were more
      of them, in spite of the fact that there were approximately 700 fewer graduates.
      In 1992 the estimated total cost per school was $25,000 (comparable data were not
      collected in 1981). The ratings of the letters revealed that only 38% of the
      schools introduced their letters as letters of "evaluation," as recommended by
      the AAMC, and that 15% of the schools failed to use the AAMC guidelines for
      format. When the schools were rated for overall quality (i.e., format combined
      with information about the students' performance in comparison with that of
      peers), 55% of the schools passed and 45% failed. CONCLUSION: Several
      recommendations for improving dean's letters are discussed, including the
      following: (1) all dean's letters should be formatted according to the AAMC
      guidelines; (2) each school should have one person responsible for central
      overview of the school's letters; and (3) for comparative performance
      information, schools should at least give the percentages of grades given in the
      required clerkships, and it would be preferable for them to employ systems that
      group students into four to six groups and to indicate the percentage of students
      in each group.

PMID- 8259965
TI  - Stability and change of interest in obstetrics-gynecology among medical students:
      eighteen years of longitudinal data.
AB  - PURPOSE: To compare the percentage of students who maintain interest in
      specializing in obstetrics-gynecology during medical school with the percentages
      of students maintaining interest in other selected specialties, and to examine
      changes of interest from obstetrics-gynecology to other specialties and from
      other specialties to obstetrics-gynecology. METHOD: A longitudinal cohort study
      comparing the stabilities of students' interests in obstetrics-gynecology and in
      other specialties was performed by using data on 3,889 graduates of 18 classes of
      Jefferson Medical College of Thomas Jefferson University between 1975 and 1992.
      RESULTS: The percentage of students who maintained interest in obstetrics
      gynecology, as measured at the beginning and end of medical school, was 19%,
      compared with 40% for internal medicine and surgery, 39% for family medicine, and
      22% for pediatrics. By the time they graduated, some students who had planned as
      freshman to pursue obstetrics-gynecology had changed their interests to internal
      medicine (19%), surgery (17%), family medicine (8%), or pediatrics (7%). In turn,
      obstetrics-gynecology attracted students who had initially expressed interest in
      other specialties: 17% from family medicine, 14% from surgery, 12% from internal
      medicine, and 8% from pediatrics. Despite the low percentage of students who
      maintained interest in obstetrics-gynecology, the overall percentage of students
      interested in obstetrics-gynecology at the time of graduation was somewhat
      greater than the percentage of students interested at the start of medical
      school. CONCLUSION: That only about one-fifth of the students initially
      interested in obstetrics-gynecology maintained their interest, and that many
      students' interests changed from one specialty to another, suggest that factors
      contributing to changes in interest need further investigation.

PMID- 8259966
TI  - Influence of a medicine clerkship conference series on students' acquisition of
      knowledge.
AB  - PURPOSE: To determine whether an intensive conference series during a third-year
      medicine clerkship would produce a significant improvement in students' standard
      scores on the National Board of Medical Examiners (NBME) medicine subject
      examination when taken at the end of the clerkship and on the medicine section of
      the NBME Part II examination when taken during the fourth year. METHOD: A
      conference series of approximately 50 hours covering core topics of internal
      medicine was begun at the Oregon Health Sciences University School of Medicine in
      1984-85. The series was repeated every 12 weeks, for each rotation of the third
      year medicine clerkship. Standard scores on the NBME medicine subject examination
      taken at the end of the medicine clerkship and the medicine section of the NBME
      II taken in the fourth year were compared between the 173 students who
      participated in the conference series in 1984-85 and 1985-86 and the 466 students
      who took the clerkship from 1980-81 through 1983-84, before the conference series
      was implemented. The students' NBME II scores in surgery and pediatrics, the
      other disciplines that had 12-week clerkships but that did not implement
      curricular changes in 1984-85 and 1985-86, were also compared, as were the
      students' scores on the NBME I, which the students took prior to the medicine
      clerkship. RESULTS: The NBME I scores were not different between the two groups
      of students. The students who took the conference series had standard scores on
      the NBME medicine subject examination that were on average 49 points higher than
      the scores of those students who did not take the conference series. This
      difference was closely maintained on the medicine section of the NBME II, on
      which the group that took the series had a mean score that was 44 points higher.
      No improvement was seen in scores on the surgery and pediatrics sections of the
      NBME II: DISCUSSION: This retrospective review of students' performances on NBME
      medicine examinations taken at the end of the third-year medicine clerkship and
      as a component of the NBME II documents a substantial improvement in performance
      for students who took an intensive conference series as a part of the medicine
      clerkship curriculum. Further, the students' improved performance level carried
      over into the fourth year.

PMID- 8259967
TI  - Clinical skills training of U.S. medical students.
AB  - BACKGROUND: Although there is general agreement that the teaching of clinical
      procedures needs vast improvement, little appears to have been done to achieve
      this goal, particularly with regard to medical students. METHOD: In the summer
      and fall of 1992, 60 U.S. medical schools participated in a telephone survey
      about how they taught clinical procedures to medical students. The schools were
      in 30 states and the District of Columbia; 36 were public and 24 were private.
      The schools were asked to describe what procedures were taught, how, and over
      what duration of time, with a focus on whether students were taught procedures
      prior to their clinical rotations. RESULTS: More than three-fourths of the
      schools (47 of 60) offered nothing other than an introduction to phlebotomy. Only
      four schools offered more extensive courses (40-50 hours) that covered a variety
      of topics. CONCLUSION: Few schools had adopted any formal method for training
      students to perform clinical procedures. In light of this problem, the authors
      describe a solution that has proven popular at the Stanford University School of
      Medicine--an elective course in surgical skills developed in 1988-89 and
      continuing to the present. Although the content of this particular course focuses
      on surgical procedures, important topics from other disciplines could easily be
      added or substituted. The course incorporates techniques that have previously
      been shown to be successful, such as the use of plastic models and cadavers. It
      also enables students to learn by performing procedures on each other, and to
      benefit from continuity of supervision by being taught by one faculty member.

PMID- 8259968
TI  - Specialty choices and practice locales of black graduates from a predominantly
      white medical school.
AB  - PURPOSE: To determine the specialty choices, practice locales, patient
      populations, and professional achievements of black graduates from a
      predominantly white medical school. METHOD: Of the 136 black graduates from the
      Medical College of Georgia School of Medicine (MCGSM) who graduated between 1971
      and 1992, 95 had completed residency training and were otherwise eligible to be
      surveyed regarding their specialty choices, practice locales, and other
      characteristics. RESULTS: Seventy of the 95 graduates (74%) responded to the
      survey, and 50 (73%) were men. Fifty-six (80%) were in primary care (including
      obstetrics-gynecology as well as family medicine, internal medicine, and
      pediatrics). Fifty (71%) practiced in their home state of Georgia, and 32 (46%)
      served low-income populations. Forty-six (66%) were board-certified, and 20 (28%)
      had faculty appointments. CONCLUSION: The black graduates of the predominantly
      white MCGSM chose primary care specialties and remained in Georgia to a greater
      extent than did other MCGSM graduates. Like their counterparts from the
      historically black medical schools, the black graduates from MCGSM--in relatively
      large percentages--chose primary care specialties and served minority patients,
      low-income populations, and/or rural areas.

PMID- 8259969
TI  - Effect of the HIV epidemic on incoming emergency medicine residents' choices of
      specialty and residency location.

PMID- 8259970
TI  - Examining whether certain Myers-Briggs "personality preferences" can be used as
      criteria to select standardized patients.

PMID- 8259971
TI  - Relationship between indebtedness and the specialty choices of graduating medical
      students: 1993 update.
AB  - The authors compared data from the 1993 AAMC Medical School Graduation
      Questionnaire (GQ) with data from earlier GQs to examine the relationship of debt
      to specialty choices among graduates of U.S. medical schools. The authors report
      the continuing increase of educational indebtedness among medical students
      graduating in 1993 compared with the debt of those graduating in earlier years,
      the greater increase in higher-level indebtedness of graduates of private medical
      schools, and the rising influence of debt on graduates who choose surgical
      specialties and support specialties. Despite the rising debt of 1993 graduates,
      however, they favored the generalist specialties more and the medical and support
      specialties less than did their 1992 predecessors.

PMID- 8259972
TI  - Morphometric quantitation of nucleolar organizer region proteins in breast
      carcinoma.
AB  - Silver-stained proteins associated with nuclear organizer regions (Ag-NORs) were
      visualized using a standard silver staining technique in biopsy specimens from
      130 breast carcinomas. The Ag-NOR protein area and perimeter (individual dots)
      were measured by image analysis, and the results were correlated with clinical,
      histologic, and quantitative prognostic factors and with survival. The mean area
      of Ag-NORs was related significantly to the degree of tubule formation (P =
      .034), histologic grade (P = .029), mean nuclear area (P = .008), SD of the
      nuclear area (P = .001), DNA ploidy (P = .015), S-phase fraction (P = .012),
      mitotic index (P = .013), and estrogen (P = .014) and progesterone receptor
      content (P = .001). The results of Ag-NOR morphometry were independent of tumor
      size and axillary lymph node status. The mean area of Ag-NORs was related to
      survival in the entire cohort (P = .07). In axillary lymph node-negative tumors,
      long Ag-NOR perimeters indicated a lower probability of survival (P = .06).
      However, in multivariate analysis, morphometry of Ag-NOR dots had no independent
      prognostic value. The results confirm previous results in that Ag-NOR protein
      quantitation was shown to have no practical prognostic value over already
      established prognostic factors in breast carcinoma.

PMID- 8259973
TI  - Grading cervical dysplasia with AgNORs using a semiautomated image analysis
      system.
AB  - Colposcopic biopsies were classified according to previously established criteria
      by a group of three pathologists interested in cervical pathology. Ten cases were
      identified in each of the following five groups: normal, koilocytosis, low grade
      squamous intraepithelial lesions (CIN 1), high grade squamous intraepithelial
      lesions (CIN 2) and high grade squamous intraepithelial lesions (CIN 3). The
      Crocker technique was used to stain the sections cut 3 microns thick. With ths
      silver stain the nucleolar organizer regions (NORs) are stained black and
      referred to as AgNORs. It has been shown that malignant and premalignant changes
      in cells produce an increase in AgNORs. In each case eight images were captured
      using a 100x oil-immersion objective and stored in a Datacube Maxvideo system as
      512 x 480 pixels in an 8-bit grayscale per image. The images were processed using
      the NeoPath field-of-view computer to detect the AgNORs and nuclei by using
      grayscale mathematical morphology algorithms. Color overlays of the AgNORs and
      nuclei were created using segmentation algorithms. The results show that it is
      possible to differentiate between low grade squamous intraepithelial lesions (CIN
      1) and high grade squamous intraepithelial lesions (CIN 2 and CIN 3) taken
      together; however, there is no difference between low grade squamous
      intraepithelial lesions (CIN 1) and koilocytosis. The results support the concept
      that dysplasia cannot be classified effectively into three grades and that low
      grade squamous intraepithelial lesions (mild dysplasia [CIN 1]) is
      indistinguishable from koilocytosis.

PMID- 8259974
TI  - Morphometric analysis of AgNORs in imprints and sections from non-Hodgkin's
      lymphomas. An approach to standardization.
AB  - The argyrophilic nucleolar organizer region (AgNOR) technique was applied to
      tissue sections and touch imprints from 20 non-Hodgkin's lymphomas (NHL). The
      mean nuclear area (NA), mean AgNOR area/nucleus (AA) and NOR percentage nuclear
      area (NPNA) were determined using image analysis. The AgNOR count, NA and AA were
      significantly higher in touch imprints than tissue sections within tumors of the
      same histologic grade. However, no significant difference was observed for NPNA
      between imprints and sections within tumors of the same grade. Both the mean
      AgNOR number and the NPNA were significantly higher in aggressive NHL (n = 10)
      than indolent NHL (n = 10), regardless of sampling method. It is suggested that
      the NPNA is invariant to the sampling technique; NPNA values from touch imprints
      and tissue sections can be compared directly. Furthermore, because NPNA is
      calculated independent of AgNOR number, it is less subjective than manual
      counting.

PMID- 8259975
TI  - Toward objective prognostic grading of prostatic carcinoma using image analysis.
AB  - At present there is no generally accepted histopathologic grading system for
      prostatic carcinoma that would be reproducible, and it is still unclear which
      system provides the most reliable individual prognosis. The objective of this
      study was to evaluate the relationship between morphometric features and
      prognosis in patients with clinical stage B prostatic carcinoma using
      computerized image analysis. Standardized histologic, Feulgen-stained slides from
      23 patients operated on for clinical stage B prostatic carcinoma were studied.
      Dimension-, form- and texture-related nuclear features, both classic and fractal,
      were computed for at least 100 nuclei per slide. Patients were divided into low
      risk and high-risk groups, using as criteria the absence or presence of
      metastases, respectively, three years after the operation. A discriminant
      function based on five chromatin texture-related features allowed complete
      separation between groups with a good or poor prognosis. These preliminary
      results, however, need to be confirmed on a larger set of patients.

PMID- 8259976
TI  - Point counting on the Macintosh. A semiautomated image analysis technique.
AB  - In image analysis, point counting is used to estimate three-dimensional
      quantitative parameters from sets of measurements made on two-dimensional images.
      Point counting is normally conducted either by hand only or manually through a
      planimeter. We developed a semiautomated, Macintosh-based method of point
      counting. This technique could be useful for any point counting application in
      which the image can be digitized. We utilized this technique to demonstrate
      increased vacuolation in white matter tracts of rat brains, but it could be used
      on many other types of tissue. Volume fractions of vacuoles within the corpus
      callosum of rat brains were determined by analyzing images of histologic
      sections. A stereologic grid was constructed using the Claris MacDraw II
      software. The grid was modified for optimum line density and size in Adobe
      Photoshop, electronically superimposed onto the images and sampled using version
      1.37 of NIH Image public domain software. This technique was further automated by
      the creation of a macro (small program) to create the grid, overlay the grid on a
      predetermined image, threshold the objects of interest and count thresholded
      objects at intersections of the grid lines. This method is expected to
      significantly reduce the amount of time required to conduct point counting and to
      improve the consistency of counts.

PMID- 8259977
TI  - Industrial developments in automated cytology as submitted by their developers.

PMID- 8259979
TI  - Synthesis and local anesthetic activity of alkylaminoacyl derivatives of 2-amino
      1,3,4-thiadiazole.
AB  - We prepared some series of 2-(alkylaminoacyl) derivatives of 2-amino-1,3,4
      thiadiazoles. Most terms were subjected to a biological screening showing a local
      anesthetic activity both in infiltration and trunkular tests. For some of the
      assayed derivatives, the activity was comparable to that of lidocaine, taken as
      the reference molecule. From the obtained results an acceptable relationship
      between some structural features and activity was drawn.

PMID- 8259978
TI  - The influence of the muscarinic receptor subtypes on the sleep-wake cycle.
AB  - The specific role played by different muscarinic receptor subtypes in sleep
      regulation is investigated and discussed. On the basis of the results obtained
      with intracerebroventricular injections of selective muscarinic antagonists into
      freely moving rats, it is suggested that each muscarinic receptor subtype induces
      different and specific changes in sleep phases and cortical desynchronization
      processes.

PMID- 8259980
TI  - 1,2-fused pyrimidines. VI. Substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones
      with antiplatelet activity.
AB  - The N-substituted 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones 2 d,g-i,l-p,r,s and
      derivatives 4,5 b,6 a,b, 7 a,b were prepared. Both these novel compounds (except
      the insoluble 7a) and compounds 2 a-c,e,f,j,k,q, 5a, previously prepared by us,
      were tested in vitro for their inhibitory activity on human platelet aggregation
      induced by ADP, collagen, or A23187. On the whole, the compounds tested proved to
      be more active towards collagen than towards ADP and A23187. The 2-(4-methyl-1
      piperazinyl)derivative 2 g was the most active compound both towards ADP and
      collagen, whereas the 2-(diethylamino)derivative 2 b proved to be the most active
      one towards A23187.

PMID- 8259981
TI  - Synthesis and pharmacological activity of 4-carbamoyl-6-beta-thienyl-4,5
      dihydropyridazin-3-(2H)ones.
AB  - A new series of 4-carbamoyl-6-beta-thienyl-4,5-dihydropyridazin-3-(2H)ones 4a-g
      have been synthesized and tested for their anti-inflammatory and analgesic
      properties. Among the tested compounds, only 4f at 1 mmole/Kg showed
      antiinflammatory activity that was comparable with that of indomethacin (5 mg/Kg)
      though of shorter duration. Compounds 4a, 4e and especially 4g at 0.2 mmoles/Kg
      displayed relevant analgesic activity, 4g being the most potent derivative in the
      writhing test. Compounds 4c and 4g were found to possess analgesic activity also
      in the hot plate test.

PMID- 8259982
TI  - Synthesis and evaluation of gastroprotective activity of omeprazole related
      benzimidazole, imidazo[4,5-b]pyridine and quinoxaline 2-substituted derivatives.
AB  - Twenty compounds possessing benzimidazole, imidazo[4,5-b]pyridine and quinoxaline
      structure bearing either a substituted arylmethylmercapto- or an
      arylmethylsulfinyl group in position 2 were prepared in order to evaluate an
      antiulcer and gastroprotective activity in rat pylorus ligature, in comparison
      with omeprazole at the dose of 50 mg/kg after i.m. administration. One third of
      these compounds showed a moderate activity, being about half potent as
      omeprazole.

PMID- 8259983
TI  - Pyrrolo[1',2':1,2]imidazo[4,5-b]pyridines, pyrrolo- [2',1':2,3]imidazo[4,5
      c]pyridines and pyrrolo[2,1-f]purines as potential benzodiazepine ligands.
AB  - The synthesis of some 7,8,8a,9-tetrahydro-6H-pyrrolo[1',2':1,2]imidazo[4,5
      b]pyridin-6-ones, 5,5a,6,7-tetrahydro-8H-pyrrolo[2',1':2,3]imidazo[4,5-c]pyridin
      8-ones and 7,8,8a,9-tetrahydro-6H-pyrrolo[2,1-f]purin-6-ones is reported. The
      structure of the obtained compounds has been assigned by means of 1H-NMR spectra
      assisted by NOESY measurements. In addition, the ability to displace [3H]
      flunitrazepam binding from rat brain membranes is determined. Only the
      pyrrolopurine derivative 5d binds to the benzodiazepine receptor (BZR) with
      appreciable potency.

PMID- 8259984
TI  - Inhibitors of Zn-dependent metallopeptidases: synthesis and activity of N-(2
      furoyl)-(Z)-alpha, beta-didehydroleucyl-L-tryptophan.
AB  - In order to gain information on structure activity relationships of peptidic
      inhibitors of Zn-dependent metalloproteinases "hemorrhagins", the
      conformationally restricted model N-(2-furoyl)-(Z)-alpha,beta-didehydroleucyl-L
      tryptophan 2 was synthesized and its activity compared to that of related
      previously studied substrates. The new model 2 exhibits an inhibitory activity on
      proteinase II from Crotalus Adamanteus snake venom, sensibly lower than that of
      related substrates. This result indicates that the reduction of the
      conformational space due to the presence of the alpha,beta-didehydro-amino acid
      residue in 2 does not favour the fitting and binding at the enzyme active site.

PMID- 8259985
TI  - Amides and formamidines with antinociceptive activity (note I).
AB  - Pursuing our investigations on N-aryl or N-cycloalkyl substituted amides and
      formamidines with antiinflammatory and/or analgesic activity, two set of
      cycloalkyl substituted amides and formamidines were prepared and tested for
      analgesic activity against a chemical stimulus. Some compounds, particularly the
      amides 7, 11, 17 and the formamidine 35 proved to be endowed with this activity.

PMID- 8259986
TI  - Amides and formamidines with antinociceptive activity (note II).
AB  - Forty amides, formamidines and trifluoromethylsulfonylamides bearing on the
      nitrogen a cyclohexyl residue, eventually 2-substituted, were prepared and tested
      for analgesic activity against a chemical stimulus. Good activity was exhibited
      by amides 9, 11 and 28, by formamidine 34, as well as by triflyamide 40. Eleven
      additional compounds exhibited a moderate activity.

PMID- 8259987
TI  - Synthesis and A1-adenosine receptors affinities of purino[7,8-c]quinazoline
      8,10(9H,11H)-diones as rigid analogues of 8-arylxanthines.
AB  - Title compounds were prepared by a cyclocondensation reaction between 8-(2
      aminophenyl)xanthines and trialkyl orthoesters. Some of them showed activities as
      A1-adenosine receptor antagonists with binding values in the micromolar range.
      Results are discussed with reference to 1,3-dialkyl-8-arylxanthines.
      Considerations on the role played by both electronic and conformational factors
      are also reported.

PMID- 8259988
TI  - Pharmacokinetics of tenoxicam at different dosage regimes.
AB  - Tenoxicam, a non-steroid anti-inflammatory of the oxicam type, has a molecular
      structure similar to that of piroxicam, but is more active and better tolerated.
      Several studies demonstrated that tenoxicam is a potent analgesic. It is
      completely absorbed after oral and intramuscular administration and slowly
      eliminated, the long half-life in tissues consenting once-daily administration.
      In the present study the pharmacokinetics of tenoxicam have been investigated
      during repeated parenteral administration, with or without loading dose, in order
      to establish the dose regime that produces constant tissue concentrations over
      time. Thirty-six patients of both sexes, suffering from acute pain due to
      arthritis of the spine, were enrolled in the study and divided into three equal
      groups. The first group was given 40 mg tenoxicam per day (single i.m. injection)
      for 2 days followed by 20 mg (single i.m. injection) for 10 days. The second
      group received 20 mg i.m. once a day for 12 days. The third group received 20 mg
      i.m. twice a day for two days followed by single 20 mg i.m. injections on the
      following days. Blood was sampled at 0, 0.5, 1,2,4,6,8,12,16 and 24 hours and at
      3,5,7,9 and 12 days. Tenoxicam levels in the samples were assayed by an HPLC
      method. The results showed that single 40 mg loading doses for 2 days, followed
      by once-daily 20 mg maintenance administration, established the requisite steady
      state tissue concentrations of tenoxicam after the second administration.
      Tenoxicam was very well tolerated in all three groups.

PMID- 8259989
TI  - Cytotoxic activity of [Pt(pyr)(N-Etlm)Cl4].
AB  - The [Pt(pyr)(N-Etlm)Cl4] complex, where pyr = pyrimidine and N-Etlm = N
      ethylimidazole, previously prepared and characterized, showed an interesting
      cytotoxicity in vitro on the human ovarian carcinoma (A2780) and on his subline
      resistant to cis-platinum (A2780/CDDP), in comparison with cis-platinum and
      carboplatinum.

PMID- 8259990
TI  - Trends in dental caries in The Netherlands.
AB  - Until 1985, epidemiological studies in The Netherlands were focused on school-age
      children. Up to that year, few caries prevalence data for (young) adults in
      selected groups were available. In 1986, the first National Dental Survey of the
      adult population was carried out in The Netherlands. Lack of information made it
      impossible for trends in dental caries in adults to be studied on a scientific
      basis. However, with use of cross-sectional studies conducted on selected adult
      populations between 1970 and 1989, an indication of a trend in dental caries is
      described. Evident changes in the age-specific average DMFT scores took place in
      the younger age groups. In the older age groups, the average DMFT score has not
      changed. Changes in percentages of edentates in the period 1980-1990 probably
      reflect part of the changes in oral health status of Dutch adults.

PMID- 8259991
TI  - Changing trends in dental caries experience in Great Britain.
AB  - Periodic national surveys of dental health since 1968, and a coordinated program
      of local surveys of children since 1985, have provided a comprehensive picture of
      trends in dental caries experience in Great Britain over the course of two
      decades. This review of some of the findings examines changes in adult caries
      experience, together with the related phenomenon of total tooth loss; presents
      evidence of a cohort effect in the decline in caries among children and young
      adults; and considers likely future trends and their implications for the dental
      services. Conclusions drawn were: (1) Although the proportion of the population
      with no natural teeth is declining rapidly among young adults, levels of
      edentulousness among older age groups will remain high for some time to come; (2)
      in England and Wales, a modest decline in caries experience of young adults
      between 1968 and 1978 accelerated between 1978 and 1988 [The greatest change in
      annual rate of reduction over two decades was in 16-24-year-olds, and in absolute
      terms, mean DMFT in this age group decreased from 15.7 to 10.4 during the
      period.]; (3) a cohort effect is discernible in the changing pattern [Thus,
      caries has apparently stabilized in young children, whereas in adolescents and
      young adults the rate of decline has increased.]; and (4) smaller improvements in
      dental health have occurred in Scotland than in England and Wales.

PMID- 8259992
TI  - Cross-sectional studies in periodontal disease: current status and implications
      for dental practice.
AB  - This paper reviews the cross-sectional national studies of periodontal disease
      conducted over the past 30 years. Studies included are the 1960-62 HES study
      (NCHS), the 1971-74 NHANES I study (NCHS), the 1981 RTI study (HRSA), and the
      1985-86 Employed Adults study (NIDR). For each of these surveys, the population
      studied, the general sampling strategy, the periodontal measures collected, and
      the periodontal findings are compared in this paper. Compared with the first
      three studies, the NIDR 1985-86 findings appear markedly lower, implying that
      there has been a decline in the prevalence of periodontal disease. Two possible
      inferences from these studies are that: (1) there has been a decline in the
      prevalence of periodontal disease in recent years or (2) the sampling and
      measurement methods may be sufficiently different for these lower numbers to
      result. Each inference is explored, with the authors concluding that the latter
      is more plausible. The implications for future treatment needs are then
      estimated, given the marked trends in the size of the aging population. The
      number of older adults over age 55 who will need periodontal services will
      increase. The adequacy of the number, type, and distribution of dental care
      providers to meet these increasing needs is discussed.

PMID- 8259993
TI  - Changing trends in adult dental disease: implications for the practitioner.

PMID- 8259994
TI  - Toward assessing trends in oral mucosal lesions: lessons learned from oral
      cancer.
AB  - Trend data on oral mucosal lesions are limited. The literature is comprised of a
      large number of studies documenting the prevalence of various lesions in
      different populations. Trend data on cancers of the oral cavity and pharynx are
      the exception. An overview of the international epidemiologic studies of these
      cancers is provided. General conclusions across studies and countries for trend
      data of these cancers cannot easily be drawn, since variations exist in data
      collection methods, risk factors, and other characteristics of the study
      populations. This paper also reviewed the available prevalence data for oral
      mucosal lesions in general as well as data on leukoplakia, recurrent herpes
      labialis, and recurrent aphthous ulcers. A few studies of the incidence of
      leukoplakia are described. In order to explore the potential for future trend
      data on oral mucosal lesions, this paper discusses issues related to the
      feasibility and structure of monitoring these lesions. Criteria that could be
      used to identify which conditions should be monitored in the future were
      discussed, such as, those that present a public health problem, those that are
      sentinel events for serious conditions, and infectious lesions. Once lesions are
      identified, it is clear that international consensus for diagnostic criteria of
      these lesions is needed in order to permit comparisons to be made among studies.
      Finally, strategies for monitoring these conditions and factors that may affect
      future trends are reviewed.

PMID- 8259995
TI  - Root caries in Scandinavia in the 1980's and future trends to be expected in
      dental caries experience in adults.
AB  - The large variety of diagnostic criteria used adds some uncertainty to
      comparisons of recent clinical and epidemiological data on root caries in
      Scandinavia. Nevertheless, it is apparent that the prevalence of frank carious
      cavities on the root among 60(+)-year-olds is about 30-40%. When inactive and
      recurrent lesions and fillings are included, the prevalence is almost 100% in
      60(+)-year-olds. At this age, the mean number of root surface fillings is about
      7, and the mean number of active caries lesions ranges from 0.9 to 3.4. The
      degree of gingival recession does not appear to be a direct measure of root
      caries risk in a population. When the number of teeth at risk is accounted for,
      the age-dependent increase in prevalence of root caries is very weak. Therefore,
      comparisons of root caries prevalence between populations are meaningful only
      when information on number of teeth present and teeth at risk is also available.
      Recent studies from various parts of the world have demonstrated that caries is
      ubiquitous in all populations and that caries progression continues throughout
      life. The impact of this on trends in prevalence and incidence of dental caries
      in adults is discussed in the light of what is known about the natural history of
      dental caries.

PMID- 8259996
TI  - The epidemiology of root surface caries: North American studies.
AB  - After some problems resulting from the lack of standardized methods in the
      conduct of root caries studies and the lack of standardized reports of findings
      are reviewed, the prevalence and incidence of root surface caries in North
      America are reviewed through a combination of epidemiologic studies and large
      clinical trials. As part of this review, the available evidence on the
      relationship between root caries and missing teeth is presented. These data lead
      to the conclusion that the prevalence and, to some extent, the incidence of root
      caries are underestimated in adults with missing teeth. This review resulted in a
      number of observations regarding the status of root caries as an oral health
      problem. First, there is little evidence that would allow conclusions regarding
      the secular increase or decrease in the prevalence or incidence of root caries to
      be drawn. Other observations gleaned include the remarkably similar prevalence
      and incidence rates obtained from the studies reviewed, positive associations
      between root caries and age, negative associations between the prevalence and
      incidence of root caries and consumption of water containing fluoride,
      indications that root caries is a problem in adults with incidence rates that
      approach caries rates in children, and associations between the prevalence and
      incidence of root caries and a wide variety of oral, behavioral, and medical
      conditions. The final observation is the need for the acceptance of conventions
      for the definition of root caries as well as the reporting of findings in order
      for more firm conclusions to be drawn from future studies.

PMID- 8259997
TI  - Trends in caries experience in US employed adults from 1971-74 to 1985: cross
      sectional comparisons.
AB  - The evidence for trends in caries experience among adults is examined by use of
      data from the NCHS NHANES I survey of dental disease, conducted from 1971 to
      1974, and the NIDR Survey of Employed Adults and Seniors, conducted in 1985 and
      1986. The main findings of the study are: (1) Mean DMF teeth and surfaces have
      declined among US employed adults who were 18-44 years old in 1985 compared with
      similar-aged persons in 1971-74; (2) differences in mean DMF teeth and surfaces
      could not be detected when persons aged 45 or older were compared; (3) missing
      and decayed components of DMF decreased in all age groups; (4) mean DF teeth
      decreased in persons under 30 years of age and mean DF surfaces in persons under
      35; (5) improvements in DMF were demonstrated by both genders and all regions of
      the US; (6) all tooth types (anteriors, premolars, and 1st and 2nd molars) showed
      improvement in DMF; and (7) while employed whites clearly demonstrated an
      improvement in DMF, a commensurate improvement among employed blacks was not
      apparent. As measured by the DMF index, caries experience declined in US employed
      adults under 45 years old between 1971-74 and 1985.

PMID- 8259998
TI  - Reliability and validity of diagnostic modalities for temporomandibular
      disorders.
AB  - Temporomandibular disorders (TMD) encompass a group of musculoskeletal conditions
      that involve the temporomandibular joint (TMJ) or joints, the masticatory
      musculature, or both. These conditions are typically characterized by pain in the
      pre-auricular area that is usually aggravated by chewing or other jaw function
      and is often accompanied, either singly or in combination, by limitation of jaw
      movement, joint sounds, palpable muscle tenderness, or joint soreness. As with
      most other musculoskeletal conditions, the diagnostic "gold standard" for TMD is
      based upon an evaluation of the patient's history and clinical examination,
      supplemented, when appropriate, by TM joint imaging. It is against this "gold
      standard" that the reliability and validity of diagnostic modalities must be
      compared. With regard to electronic devices, several reviews of the scientific
      literature have concluded that the diagnostic reliability, validity, sensitivity,
      and specificity of such devices in the diagnosis of TMD have not been
      established. In addition, although clinical examination of the dentition may
      provide useful diagnostic information for some conditions, specific occlusal
      relationships have poor sensitivity and specificity when related to the presence
      or absence of TMD. TMJ imaging, when indicated, is useful in the detection of
      pathology within the joint, provided that validated criteria are applied to an
      analysis of the image. However, the assessment of condylar position as a
      diagnostic criterion for TMD has very poor reliability and validity.

PMID- 8259999
TI  - Diagnosis of intracapsular pathology associated with temporomandibular joint
      disorders.
AB  - The clinical diagnosis of a Temporomandibular Disorder (TMD) has traditionally
      been based on data gathered by means of a medical history and physical
      examination. The most common signs and symptoms associated with TMD are reduced
      jaw opening, pain and elevated tenderness in the muscles of mastication, pain and
      elevated temporomandibular joint (TMJ) tenderness, and TMJ noises upon movement.
      These signs and symptoms are routinely detectable by a skilled clinician upon
      examination. Unfortunately, the clinical problem described globally as a TMD has
      several different and overlapping patho-physiologic disease processes, and a
      traditional clinical examination does not provide highly tissue-specific
      pathologic information. Were it readily available, such information would be
      greatly useful, since logical and accurate treatment planning requires that each
      disease process be correctly identified. One important challenge for researchers
      interested in TMD will be the careful definition and subsequent validation of
      diagnostic methods which identify the relevant ongoing pathological disease
      process. On such research area, which has great promise, is the establishment of
      a valid diagnostic technique for intracapsular pathologies unique to TMD
      patients. This paper provides a critical review and discussion of the diagnostic
      validity of TMJ arthroscopy and other related methods of identifying
      intracapsular pathologies associated with TMD.

PMID- 8260000
TI  - Temporomandibular disorders: assessment of psychological factors.
AB  - Factors such as psychological stress, anxiety, depression, oral habits, and
      chronic pain behaviors have been found in subgroups of Temporomandibular
      Disorders (TMD) patients. This paper reviews the current status of diagnostic
      methods and instruments designed to identify various psychological factors. The
      authors offer the following general conclusions: Although the DSM-III-R has
      significant limitations, it is currently the most common gold standard with which
      other psychological instruments are compared. There are several specific
      assessment instruments, such as the Beck Depression Inventory and the Zung Self
      Rating Depression Scale, which have been found to have acceptable sensitivity and
      specificity scores. In addition, certain simple screening questions may be cost
      effective for the identification of psychological factors. Because of studies
      indicating that the dentists' recognition of psychological factors is inaccurate,
      a brief screening questionnaire may be useful in TMD patients. The literature
      does not support the routine use of the MMPI. A major conclusion of this review
      is that there are several psychological instruments available which have
      demonstrated reasonable validity through a blind comparison with a gold standard.
      There is need for further development and testing of brief screening instruments
      using clinical decision methods.

PMID- 8260001
TI  - Reliability and validity of imaging diagnosis of temporomandibular joint
      disorder.
AB  - The purpose of this article is to review reliability and validity of imaging
      diagnosis of temporomandibular joint disorders. Plain-film and tomography are
      basic imaging techniques for assessment of the temporomandibular joint. These can
      be used for evaluation of osseous disease and as a baseline for follow-up. In
      patients with symptoms from the joint, plain-film and tomography are rarely
      definitive, and evaluation of the soft tissues is frequently necessary.
      Arthrography, computed tomography, and magnetic resonance imaging have all been
      used for evaluation of the soft-tissue components of the joints. Accuracy studies
      of these techniques have demonstrated the highest diagnostic accuracy for
      magnetic resonance imaging. Arthrography is relatively insensitive for detection
      of medial and lateral displacements. Magnetic resonance imaging accurately
      depicts both hard and soft tissues, and this technique is emerging as the prime
      diagnostic imaging technique in patients presenting with clinical signs and
      symptoms of a disorder of the temporomandibular joint. The most frequent findings
      when patients with clinical symptoms of temporomandibular joint disorders are
      "imaged" are different forms of disc displacement and degenerative joint disease.
      Studies have demonstrated a high prevalence of different forms of disc
      displacement in patients, although these abnormalities are also seen in some
      asymptomatic volunteers. Future research should further refine imaging techniques
      to come closer to an understanding of the association between morphologic
      alterations and patient symptoms.

PMID- 8260002
TI  - The strategy and advantage in use of an electronic probe for attachment
      measurement.
AB  - Attachment level has been used as the "gold standard" for assessment of the
      progression of periodontal disease. However, the measurement of attachment level
      by periodontal probing can be subject to a large number of error sources.
      Recently, we have designed experiments by using an electronic probe to identify
      the magnitude of error components due to the instrument, gingival tissue
      condition, position or probing angle, and time interval between replicate
      probings. Even with a very careful clinical setting, a few percent of
      uncontrollable large errors or outliers could not be avoided. A previously used
      'option-3' probing scheme to reduce the unexpected large error is justified from
      the mathematical viewpoint.

PMID- 8260003
TI  - Modern radiographic methods in the diagnosis of periodontal disease.
AB  - For many years, radiographs have been a valuable aid in the diagnosis of
      periodontal disease and the evaluation of treatment effects. Computer-based image
      acquisition and processing techniques will now further increase the importance of
      radiography in periodontal diagnosis. Temporal changes of lesions can be made
      easily visible by means of subtraction radiography based on digital images. This
      process requires a pair of images with identical gray-level distributions and
      projection geometry. The gray-level distribution and perspective projection of
      images can be corrected by means of digital image processing. A pair of identical
      images can thus be obtained without mechanical alignment of patient, film, and x
      ray source. Algorithms have been developed for automatical determination of the
      borders of lesions and can subsequently produce quantitative information ranging
      from simple distance measurements to advanced multidimensional quantitation of
      image parameters. Accurate volume measurements can be carried out by the
      utilization of calibration wedges in the image. Image reconstruction procedures,
      such as tomosynthesis, provide information about the third dimension, which is
      normally lost in conventional radiographic projections. The buccal and lingual
      sites of the alveolar crest can be inspected separately. The progress of computer
      aided procedures as discussed in this paper appears to have great potential for
      the improvement of the radiographic diagnosis of periodontal lesions. Especially,
      the benefits of reproducibility and quantitative evaluation of treatment effects
      will greatly improve the role of radiography in periodontics.

PMID- 8260004
TI  - Role of suspected periodontopathogens in microbiological monitoring of
      periodontitis.
AB  - Periodontal disease is the clinical result of a complex interaction between the
      host and plaque bacteria. Although a specificity to some degree is found for
      Actinobacillus actinomycetemcomitans in localized juvenile periodontitis (LJP),
      it has been difficult to obtain evidence for a specific etiological role of the
      bacteria associated with periodontal disease in adults. What we see is the net
      result of host-parasite interactions which in an unpredictable moment accumulate
      and exceed the threshold of tissue integrity. This hypothesis is concomitant with
      the view of periodontal disease as a polymicrobial infection, predominantly
      anaerobic, which occurs commonly in the oral cavity or elsewhere in the body.
      Some micro-organisms (risk markers) occur more frequently than others and may
      significantly determine the outcome of this host-parasite interaction.
      Microbiological sampling and analysis seem to be of limited value in risk
      assessment; however, they can be used as tools in diagnosis in LJP patients and
      acute infections, and in treatment decision and therapy control in "refractory"
      patients. Suspected pathogens (risk markers) are Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis, and some species of spirochetes,
      while the roles of Prevotella intermedia, Bacteroidesforsythus, Fusobacterium
      nucleatum, Campylobacter rectus, and Peptostreptococcus micros are more
      uncertain. The presence of periodontopathogens as well as enterics,
      Staphylococcus aureus and Candida especially, should be considered in patients
      with systemic individual disorders--e.g., diabetes mellitus, neutropenia,
      agranulocytosis, and AIDS--or with implants.

PMID- 8260005
TI  - Diagnostic potential of host response mediators.
AB  - This review summarizes the data which relate the validation and application of
      host response markers as diagnostic tests for periodontal diseases. Practical
      considerations regarding the general application and evaluation of a diagnostic
      test for periodontal disease are presented. Experiments which have documented the
      performance of host response markers as diagnostic measures of disease activity
      in terms of sensitivity, specificity, and predictive values are summarized.
      Particular emphasis is placed on the diagnostic potential of gingival crevicular
      fluid (GCF) components. The considerable body of evidence supporting the
      potential application of GCF-PGE2 levels for predicting episodes of disease
      progression and reflecting disease activity is summarized and placed into
      perspective for the development of future diagnostic tools.

PMID- 8260006
TI  - Current status of tests for periodontal disease.
AB  - The methods applied to the diagnosis of periodontal disease are changing.
      Historically, static clinical and radiographic parameters have formed the basis
      of the periodontal evaluation. As the limitations of these traditional procedures
      became clear, several new techniques have been proposed as diagnostic tests for
      periodontal disease. These tests are based on improved understanding of the
      pathogenesis of periodontal disease, and can be considered in three categories:
      assessment of physical changes in the periodontium, the bacterial infection, and
      the host response to the infection. Several technical questions must be addressed
      before these tests can be widely utilized. These specific concerns include such
      matters as the information available from the tests (e.g., Does the test provide
      a measure of disease severity or identify the site, region, or patient
      experiencing active disease?), the most appropriate test configurations, the
      statistical analysis of data from trials examining the accuracy of the tests, and
      selection of patients who would benefit from these procedures. Last, several
      important practical issues must be examined before these tests can be expected to
      gain widespread acceptance. These include familiarization of dental practitioners
      with the use of diagnostic tests and the medical laboratory, the role of
      regulatory agencies in determining the claims made by these tests, and the
      medical/dental insurance benefits provided for these services.

PMID- 8260007
TI  - Reproducibility and detection threshold of peri-implant diagnostics.
AB  - There is an increasing awareness that, for clinical monitoring of oral implants,
      there is a need for reliable diagnostics and possibly prognostic parameters.
      Indeed, reports have too often limited results to an inventory of failures, while
      no mention was made of progressive marginal bone loss or other symptoms of a
      future failure. Several parameters, such as marginal bone level assessment and/or
      probing attachment level, give a precision of up to 0.5 mm. Both measurements
      also seem related. The damping characteristics of the individual implant/bone
      unit also offer a highly reproducible diagnostic tool. The Periotest allows for
      detection of subclinical mobilities, and 95% of repeated measurements fall within
      a range of one unit on the arbitrary scale. So far, these three parameters offer
      no prognostic value.

PMID- 8260008
TI  - Digital subtraction radiography for longitudinal assessment of peri-implant bone
      change: method and validation.
AB  - The purpose of this paper is to present a digital subtraction technique for the
      assessment of peri-implant bone change over time in vivo. Digital subtraction
      radiography may be used to detect areas of bony change that have occurred between
      radiographic examinations, and image processing algorithms have been developed
      which can relate the magnitude of the change on the subtraction image to a
      reference wedge, thereby allowing calculation of the mass of the lesion. This
      manuscript will present two algorithms for the assessment of osseous change. The
      method was validated in monkeys by means of small bony chips placed intra-orally
      prior to the first radiograph. The chips were removed, a second radiograph taken,
      and the images subtracted. Each algorithm was used to isolate the lesion and
      calculate change in bone mass. Overall, there was excellent correlation between
      the calculated lesion mass (in milligrams) and actual lesion mass (r2 > 0.9). The
      utility of the method was demonstrated by comparison of the results of
      subtraction radiography in successful implants and in implants that did not
      integrate during the healing phase.

PMID- 8260009
TI  - Microbiology of the dental implant.
AB  - Longitudinal studies have shown that successful implants are colonized by a
      predominantly Gram-positive, facultative flora, which is established shortly
      after implantation. Repeated microbiological sampling in patients with clinically
      stable implants showed no significant shifts in the composition of this flora
      over five years. In patients with bone loss and pocket formation around implants,
      however, a significantly different flora was found: Gram-negative anaerobic
      bacteria, particularly fusobacteria, spirochetes, and black-pigmenting organisms
      such as Prevotella intermedia were often present in high proportions.
      Antimicrobial treatment with agents specifically active against anaerobes could
      halt progression of peri-implant infections in such cases. Although there may be
      non-microbial primary causes for implant failure, these studies show that Gram
      negative anaerobes may play a role in peri-implant infections, and that their
      elimination leads to improvement of the clinical condition.

PMID- 8260010
TI  - New approaches to the diagnosis of oral soft-tissue disease of viral origin.
AB  - Molecular biology is changing the face of diagnostic medicine, and infectious
      diseases of the oral soft tissues are among the targets of these advances in
      biotechnology. As an illustration of these concepts, a PCR-based detection and
      typing system for human papillomaviruses (HPVs) will be discussed. A single
      "consensus" set of oligomeric nucleotide primers can be used to amplify a 571- to
      594-base-pair region of the E1 open reading frame of HPV 6, 11, 16, and 18. These
      HPV types are commonly associated with preneoplastic and cancerous lesions of the
      genital, respiratory, and digestive tracts. PCR amplification yields single bands
      of similar size for these viruses by agarose gel electrophoresis. Digestion of
      the resultant products by the restriction endonuclease AccI yields distinctive
      and reproducible banding patterns by polyacrylamide gel electrophoresis (with
      ethidium bromide) due to their internal sequence diversity. The system is
      sensitive; without radioisotopes, it can detect and type HPV 18 in as little as
      100 pg of DNA from HeLa cells. We have used it to confirm HPV in fresh-frozen
      tumors. Computer sequence analysis can be used to modify the system for the
      detection of new HPV types as they are characterized. Other applications of
      molecular-biology-based detection systems for infectious diseases of the head and
      neck region will be discussed.

PMID- 8260011
TI  - Non-infectious diseases of the oral soft tissue: a new approach.
AB  - A significant proportion of the non-infectious diseases of oral mucosa are either
      auto-immune in nature or have lesions which are the result of immunologically
      mediated events. These include pemphigus, benign mucous membrane pemphigoid,
      linear IgA bullous dermatosis, dermatitis herpetiformis, epidermolysis bullosa
      acquisita, erythema multiforme, and lichen planus. Although each of these has
      certain specific characteristics, all may produce bullae, erosions, and ulcers on
      the oral mucosa, resulting in confusingly similar clinical presentations. With
      careful clinical, histological, and immunofluorescence examination, it is
      possible to establish a definitive diagnosis in a high proportion of cases.
      However, one of the most exciting developments which has emerged from recent
      research into these diseases is their precise molecular characterization. This
      raises the prospect of accurate, highly specific diagnostic tests which would
      provide the basis for sound clinical management, with original approaches
      replacing the somewhat unsatisfactory symptomatic treatment which is often all
      that is available.

PMID- 8260012
TI  - New approaches for determining the site of salivary fluid secretory disorders.
AB  - Considerable progress has been made in understanding the events which underlie
      salivary fluid secretion. We have utilized novel approaches to evaluate the
      functional status of three distinct sites in the secretory cascade. First,
      salivary sympathetic nerve function studies used isotopic dopamine to measure
      catecholamine uptake and metabolism in vivo. Second, salivary muscarinic
      cholinergic receptors were characterized in vivo by use of stereo-specific
      ligands and pharmacokinetic analyses. Finally, microfluorometric methods were
      used to study intracellular Ca2+ signaling in dispersed cells prepared from
      biopsied tissue. We conclude that it is possible to determine the functional
      status of key steps in salivary fluid generation with isotopic and fluorometric
      imaging techniques.

PMID- 8260013
TI  - Evaluating diagnostic tests.
AB  - The presentations at this conference will discuss new technologies and rapid
      scientific developments that have resulted in new diagnostic tests for
      periodontal disease, musculoskeletal imaging, temporomandibular joint
      dysfunctions, and incipient coronal and root dental caries. However, for many of
      these claims, there has been insufficient scientific support regarding the
      sensitivity and specificity of the tests, or their ability to predict the percent
      of cases in which the disease or condition progresses to the next state of
      development. Research is needed that will yield the basic diagnostic parameters
      of new diagnostic tests, i.e., their accuracy, precision, sensitivity,
      specificity, positive predictive value, and negative predictive value. The
      purpose and methods for calculating each of these measures are described in this
      paper. Five questions are then presented that will need to be addressed in future
      research regarding new diagnostic tests: (1) Does the scientific theory of the
      test fit with our current body of knowledge? (2) Have the efficacy parameters of
      the test been reliably determined? (3) How does the test affect clinical decision
      making? (4) Does using the test improve the patient's health? and (5) Is the
      added expense of the test justified by increased effectiveness or by avoiding
      other health expenditures?

PMID- 8260014
TI  - Advances in methods for diagnosing coronal caries--a review.
AB  - Diagnostic methods for coronal caries in common use include visual inspection,
      tactile examination with a probe, bite-wing radiography, and often fiber-optic
      transillumination (FOTI). Early diagnosis enables small lesions to be identified
      so that remineralization of lesions by preventive measures can be attempted; in
      clinical research, it may shorten the time for clinical trials. Quantitative
      methods may potentially decrease interexaminer variations and facilitate the
      determination of small progressions or regressions. This review discusses recent
      advances in the development of such methods, i.e., endoscopic methods, FOTI,
      light-scattering, laser fluorescence, ultraviolet illumination, penetration of
      dyes, iodide penetration, electrical resistance, ultrasonic imaging, and improved
      radiographic imaging techniques. Diagnosis of occlusal surfaces gains from the
      use of the electrical resistance method (preferable when the emphasis is on
      finding lesions) or radiography (when the emphasis is on identifying sound
      surfaces). Digitized radiography with simple contrast enhancement gives some
      further improvement. Quantitative methods are not yet proven to be good enough to
      measure small changes. Quantitative methods are not yet proven to be good enough
      to measure small changes. For occlusal surfaces, the electrical resistance method
      may be, but this has to be confirmed. For approximal surfaces, digitized
      radiography and fluorescent dye penetration have to be tested for clinical
      feasibility. It is concluded that there are many methods in development, but all
      require clinical testing, and many still need development before clinical use.

PMID- 8260015
TI  - Diagnosis and prediction of root caries.
AB  - Diagnosis is the process of recognizing diseases by their characteristic clinical
      signs and symptoms. Diagnostic ability varies considerably between and among
      examiners, and, consequently, the accuracy of the diagnosis can be questioned.
      Root caries is a disease for which there are several clinical signs (location,
      color, surface texture, and surface cavitation). Unfortunately, these signs are
      open to broad clinical interpretation. As a result, estimates of disease
      occurrence (incidence rate) have ranged from 0.87 to 8.20/100 surfaces at
      risk/year or 0.15 to 0.43 lesions/person/year for adults living independently in
      the community. When multiple examiners are utilized, interexaminer agreement has
      been reported to be relatively good but could be further improved by minimizing
      the effects of several sources of examiner disagreement, including the absence of
      a global consensus on the signs which indicate the presence of root caries. The
      use of a diagnostic test can enhance the diagnosis and prediction of root caries,
      but the development of useful tests is hindered by the lack of an accurate
      clinical standard of diagnosis. At this time, diagnostic tests for root caries
      are quite limited and of questionable value. A powerful predictive tool for root
      caries would result from the combination of risk assessment measures and a valid
      diagnostic test developed with use of standardized and accurate methods of
      clinical diagnosis.

PMID- 8260016
TI  - Microbiological predictors of caries risk.
AB  - The prediction of caries risk has been of long-standing interest. Generally, few
      of the tests involving oral bacteria or their products have become accepted.
      Presently, the main focus is on counts of lactobacilli (L) and mutans
      streptococci (MS). Due to their positive numerical association with human caries
      and the linkage of this association to carbohydrate consumption, counts of L and
      MS may, potentially, serve not only as a caries risk predictor but also as an
      indicator of carbohydrate consumption, another caries-risk factor. The value of
      counts of L and MS as caries-risk predictors has been evaluated by means of
      studies providing data on test sensitivity, specificity, and predictive values.
      These and other studies indicate that their use for the prediction of caries risk
      of individuals is not possible but is more promising for that of the caries risk
      of groups (e.g., identification of high-caries-risk subjects); further, the
      prediction of low caries risk may be more reliable than that of high caries risk.
      The influence of test variables on the test results has been discussed. These
      include the level of caries increment, subject age, methods of caries evaluation,
      use of saliva or dental plaque as test sample, sampling frequency, type of
      bacterial growth medium, and the use of simplified methods rather than
      conventional laboratory procedures for microbial enumeration. An approach to
      optimize the use of microbiological caries-risk predictors in different
      populations as well as their use in conjunction with other caries-risk predictors
      has been discussed. The latter include the incipient caries lesion or past caries
      experience and salivary buffering capacity and flow rate. Due to the
      multifactorial nature of caries etiology, it is expected that multivariate
      approaches rather than the use of single parameters may improve caries risk
      prediction for individuals as well as groups of subjects.

PMID- 8260017
TI  - The utility and validity of current diagnostic procedures for defining
      temporomandibular disorder patients.
AB  - This paper describes the evolution of different concepts of classifying and
      defining Temporomandibular Disorders (TMD) for both clinical and research
      settings. The literature is reviewed with respect to the utility and validity of
      the different questionnaire and examination procedures that have been used to
      assess TMD patients. The presented view is that many of these procedures have not
      been validated, that there is a lack of standardization in the use of the
      procedures themselves, and that an ideal method of classifying this broad group
      of patients into better-defined subgroups has not yet been developed. More
      standardized and better-defined research by trained and calibrated researchers is
      needed worldwide to elucidate these subgroups so that a better and widely agreed
      upon research classification system can be developed for widespread use. It also
      seems clear that as research requirements for defining TMD patient subgroups
      become more stringent over time, it may not be practical for the clinician to
      implement them on a day-to-day basis in his or her practice. As such, a practical
      utilitarian definition of the common subtype of TMD patients is also needed which
      parallels any research grouping, so that data from research are valuable and
      generalizable to the practicing clinician.

PMID- 8260018
TI  - Transforming growth factor beta as an immunosuppressive protein in human seminal
      plasma.
AB  - PROBLEM: Human seminal plasma is known to exhibit immunosuppressive activity in
      seminal plasma. PURPOSE: The purpose was to characterize immunosuppressive
      proteins in seminal plasma. METHOD: Gel filtration fractions of 100 to > 440 kDa
      were identified that inhibited DNA synthesis and killing activity of interleukin
      2 stimulated lymphocytes. RESULTS: The fractions exhibiting immunosuppression
      also inhibited DNA synthesis in a mink lung cell bioassay commonly used to
      measure the activity for transforming growth factor beta (TGF-beta). The negative
      growth activity was diminished by a TGF-beta neutralizing monoclonal antibody.
      TGF-beta was further detected in the active fractions by Western immunoblot.
      CONCLUSIONS: These results identified TGF-beta as an immunosuppressive protein in
      human seminal plasma and may provide insight into the role of immunosuppression
      played by seminal plasma, such as in reproduction and neoplasia.

PMID- 8260019
TI  - GnRH agonist induces suppression of lymphocyte subpopulations in secondary
      lymphoid tissues of prepubertal female mice.
AB  - PROBLEM: Gonadotropin-releasing hormone (GnRH) agonists are playing an increasing
      role in the medical management of a variety of diseases. Recent evidence also
      indicates GnRH immune system interactions. METHOD: The present study investigated
      the sequential changes in lymphocyte subpopulations in secondary lymphoid tissues
      of prepubertal female mice in vivo following Lupron depot administration. A
      direct two-color immunofluorescence staining followed by flow cytometric analysis
      was employed. RESULTS: Following agonist administration, white blood cell counts
      decreased significantly with decreases in both granulocyte and lymphocyte counts.
      Blood T-cell and B-cell subsets were also reduced although B cells decreased more
      markedly. In the spleen, B cells were again reduced more than T cells. There was
      no selective loss of either CD4 or CD8 subpopulations at any time point, in both
      spleen and blood. There were no differences in the percentage of lymph node
      subsets except that B cells decreased in the second week. CONCLUSIONS: These data
      indicate that GnRH agonist alters specific lymphocyte subpopulations and,
      therefore, have the potential for affecting immune system function in vivo.

PMID- 8260020
TI  - No detection of interferon-gamma activity during early pregnancy in the mouse.
AB  - PROBLEM: Interferons (IFN) have been shown to be secreted by the trophectoderm of
      implanting embryos in different species, in particular ungulates. In the pig, a
      clear-cut IFN-gamma production, the role of which is unknown, was found in the
      trophoblast at implantation. A murine counterpart to these IFNs has not yet been
      identified. METHOD: Two sets of experiments were conducted to test the presence
      of IFN-gamma in the mouse conceptus. First, day 4 blastocysts were collected from
      Swiss mice and their antiviral activity measured in a microassay using mouse L
      929 cells and vesicular stomatitis virus (VSV) in the presence or absence of anti
      IFN-gamma antibodies. In a second set of experiments, uteri from Swiss mice on
      days 5.5 and 6.5 of pregnancy were flushed and the resulting fluids assayed in a
      specific and sensitive ELISA test. RESULTS: In the antiviral assay, no consistent
      IFN-like activity was found. The viral challenge also revealed a high
      susceptibility of mouse blastocysts to VSV infection. By ELISA, all but two
      samples (N = 75), whether on 5.5 or 6.5, were found negative. CONCLUSIONS: We
      conclude that in this rodent species IFN-gamma is most probably not involved in
      early maternal-fetal interactions.

PMID- 8260021
TI  - Treatment of recurrent spontaneous abortions by immunization with paternal
      lymphocytes induces immunosuppression by placental isoferritin.
AB  - PROBLEM: The immunological mechanism leading to an effective vaccination of
      unexplained habitual aborters with paternal lymphocytes is not yet elucidated.
      Since previous studies revealed that immunosuppression by placental isoferritin
      (PLF) may play an important role in the down regulation of the immune system
      during pregnancy, it was of interest to investigate whether alloimmunization
      activates immunosuppression by PLF. METHOD: The immunosuppressive effect of PLF
      or anti-PLF CM-H-9 monoclonal antibody (MAb) was studied by a one-way mixed
      lymphocyte reaction (MLF) of alloimmunized women and their husbands. RESULTS: It
      was found that vaccination of the women with paternal lymphocytes resulted in in
      vitro immunosuppression by PLF as well as by CM-H-9 MAb, reaching the highest
      effect after three vaccinations (38 +/- 8 and 42 +/- 10%, respectively). The
      increase in PLF immunosuppressive effect was accompanied by the appearance of
      serum antipaternal human leukocyte antigen cytotoxic antibodies. However, there
      was no correlation between the degree of suppression and titer of antibodies. The
      study group was too small to reach a significant correlation between degree of
      immunosuppression and pregnancy outcome. CONCLUSIONS: Although it may be of value
      to measure the inhibitory effect of PLF in one-way MLR as an index of
      immunosuppression, further studies are needed to establish whether it is a
      relevant predictor of a successful pregnancy.

PMID- 8260022
TI  - Recurrent spontaneous abortion: histocompatibility between partners, response to
      immune therapy, and subsequent reproductive performance.
AB  - PROBLEM: Immunological factors may account for previously unexplained cases of
      recurrent abortion. METHOD: After screening 76 couples for causes of recurrent
      spontaneous abortion and measuring maternal antipaternal immunity, 23 primary
      spontaneous recurrent aborters were immunized once with their husbands'
      leukocytes. Testing for antipaternal cytotoxicity was repeated in 21 couples.
      Seroconversion was significantly less frequent in couples who shared more than
      one human leukocyte antigen [one of five (20%) versus 13 of 16 (81%), P < .02].
      RESULTS: Twelve of 16 women (75%) who became pregnant had live children and five
      of those have had a second live child. All 12 women who achieved successful
      pregnancies had become antipaternal cytotoxic antibody-positive after
      immunization, whereas all four patients who had repeat abortions had failed to
      seroconvert (P < .001). However, this relationship is not necessarily causative,
      as the successful group also tended to have fewer previous abortions and less
      human lymphocyte antigen sharing. CONCLUSION: Except for transient illness after
      immunization, one moderately small for gestational age baby and one premature
      labor at 32 wk, no complications were observed after immunization.

PMID- 8260023
TI  - Report from the Ethics Committee for Immunotherapy.

PMID- 8260024
TI  - Lack of expression of HLA antigens on immature germ cells from ejaculates with
      antisperm antibodies.
AB  - PROBLEM: The lack of expression of HLA antigen on immature germ cells from
      ejaculates with antisperm antibodies has been reported. METHOD: The expression of
      human leukocyte antigens on immature germ cells from ejaculates with antisperm
      antibodies (ASA) was investigated by indirect immunofluorescence using a panel of
      monoclonal antibodies (MAb) and automated flow cytometry. Patients were divided
      into two groups: fertile (prevasectomic; N = 10), and ejaculates with ASA (10
      samples with IgG and IgA ASA, and five semen samples with only IgG ASA). ASA were
      detected on sperm using the direct immunobead test. After centrifuging semen
      samples on a Ficoll-Hypaque gradient, round cells obtained at the gradient
      interface were gated by a flow cytometer. The "immature germ cell window" was
      defined in terms of cellular volume and granularity. RESULTS: The percentage of
      gated round cells from semen samples that reacted with anti-CD45 was always less
      than 5%, and with anti-CD44 less than 3%. This lack of reactivity of gated round
      cells with MAb specific for leukocytes and epithelial cells suggests that they
      were immature germ cells. Immature germ cells were unreactive with W6/32 and anti
      beta-2-microglobulin MAb, which suggests that these cells do not express HLA
      class I molecules. Similarly, no reactivity of the immature germ cells with the
      MAb that recognize HLA class II molecules was found. No significant differences
      were observed in the expression of HLA molecules on immature germ cells between
      the different semen samples studied: fertile, and ejaculates with ASA.
      CONCLUSION: The presence of ASA in ejaculate is not associated with abnormal HLA
      antigen expression on immature germ cells.

PMID- 8260025
TI  - Breastfeeding research priorities, opportunities, and study criteria: what we
      learn from the smoking trail.

PMID- 8260026
TI  - The need for "civil" maternity leaves.

PMID- 8260027
TI  - When babies accept only the breast: what to do?

PMID- 8260028
TI  - Femininity: something to reject or rejoice in?

PMID- 8260030
TI  - Validation that support increases breastfeeding duration.

PMID- 8260029
TI  - Breastfeeding and the ovulation method of natural family planning.

PMID- 8260031
TI  - Twenty cases of persistent sore nipples: collaboration between lactation
      consultant and dermatologist.
AB  - The nipple and surrounding area, like other areas of skin, are subject to
      irritation, inflammation, and infection. Twenty women with persistent sore
      nipples were first seen by a lactation consultant and later referred to a
      dermatologist. The dermatologist successfully treated 18 of the 20 mothers. A
      lactation consultant should be able to identify those women who will benefit from
      evaluation and treatment by a dermatologist.

PMID- 8260032
TI  - The effects of breast reduction and breast augmentation surgery on lactation: an
      annotated bibliography.
AB  - An annotated bibliography reviews journal literature, some medical texts and
      sources cited therein, from the past ten years on the subject of the effects of
      breast reduction and breast augmentation surgery on the ability to lactate. Far
      more information is available about the relationship of breast reduction surgery
      and lactation than about breast augmentation surgery and lactation. Women are
      often able to breastfeed after breast augmentation surgery. Depending upon the
      type of breast reduction surgery, estimates of the number of women who can
      lactate after reduction surgery range from zero to 70 percent.

PMID- 8260033
TI  - Helping the woman who has had breast surgery: a literature review.
AB  - Women who have had breast surgery are likely to have many questions and
      misgivings about their ability to breastfeed. In order to answer the woman's
      questions and provide her with supportive and guiding care, the lactation
      consultant must understand the nature of the surgery, the reasons for it, and the
      likely outcome with respect to the ability to lactate.

PMID- 8260034
TI  - Eczema of the nipple and breast: a case report.

PMID- 8260035
TI  - Breastfeeding difficulties and a breast abscess associated with a galactocele: a
      case report.

PMID- 8260036
TI  - There's a fungus among us!
AB  - Candida infections can be extremely persistent and often are a source of
      considerable frustration for parents and professionals. Appropriate management of
      the initial infection is critical. Too often the treatment is inadequate or
      carried out for too short a period. A fungus is an amazing organism, deceptive in
      its simplicity, tenacious in its adaptability. Management of candidiasis
      challenges the lactation consultant to provide not only assessment and
      intervention but reassurance and reassessment in order to preserve the
      breastfeeding relationship.

PMID- 8260037
TI  - Passionate advocacy: a look back, a look forward.

PMID- 8260038
TI  - Post-feed breast pain: a case report.

PMID- 8260039
TI  - A captive audience for breastfeeding information.

PMID- 8260040
TI  - Topical medications and breastfeeding.
AB  - Little data are available regarding the topical application of drugs to breast,
      nipple, or areolar tissue. Absorption of therapeutic agents applied to the breast
      may be of concern in the breastfed infant. Absorption may occur by direct contact
      with the drug while nursing, or by milk levels of the drug attained from systemic
      absorption. The safety of each individual agent should be assessed prior to
      application to the breast while nursing.

PMID- 8260041
TI  - Can a woman breastfeed while using Depo-Provera as an agent for birth control?

PMID- 8260042
TI  - The establishment of a human milk bank in India.

PMID- 8260043
TI  - Red Cross home nursing. 1942.

PMID- 8260044
TI  - Breastfeeding promotion in the Utah WIC program.
AB  - The Utah WIC program has implemented a variety of breastfeeding promotion
      activities and programs designed to encourage more mothers to initiate and
      continue breastfeeding. These activities include training WIC staff in
      breastfeeding management and support, updating educational materials,
      implementing peer counseling programs, meeting to coordinate breastfeeding
      promotion, purchasing breastfeeding equipment, and coordinating a statewide
      breastfeeding coalition. Since 1989, the breastfeeding initiation rate in the
      Utah WIC program has improved 17 percent, and breastfeeding at six months has
      increased nine percent. Breastfeeding promotion activities will continue to
      promote breastfeeding among WIC mothers in Utah.

PMID- 8260045
TI  - A dozen commandments for lactation consultants: an offering of love.

PMID- 8260046
TI  - Breastfeeding and maternal employment: another perspective.

PMID- 8260047
TI  - New WIC food package for women who are breastfeeding exclusively.

PMID- 8260049
TI  - Appropriate infant feeding terminology.

PMID- 8260048
TI  - ASPO/Lamaze decision regarding support of breastfeeding.

PMID- 8260050
TI  - Syringe treatment for nipples works!

PMID- 8260051
TI  - To wean or not: help from the workplace.

PMID- 8260052
TI  - Fathers and breastfeeding.

PMID- 8260053
TI  - Where assessment tools are best suited for use.

PMID- 8260054
TI  - Evaluation of a breastfeeding protocol.
AB  - A breastfeeding protocol has been field-tested in three hospitals. A pre- and
      post-test design was utilized to measure breastfeeding knowledge of health
      professionals and mothers before and after implementation of a standard
      breastfeeding protocol. Although results demonstrated a statistically significant
      increase in knowledge scores for health professionals and mothers, actual change
      in score was less than two percent and one percent respectively, compared to
      preintervention scores. Scores of both groups were not high and indicated limited
      knowledge in the health professional group in particular. Despite the fact that
      protocol implementation did not significantly alter knowledge scores, it did
      initiate positive changes in policies and procedures which may continue to
      influence knowledge and practice of health professionals.

PMID- 8260055
TI  - Support network utilization by breastfeeding mothers.
AB  - The Utilization of Support Network Questionnaire (USNQ) was developed to
      determine how mothers utilize their network for successful breastfeeding. Sixty
      breastfeeding mothers completed the USNQ. Lactation consultants were the most
      utilized resources for providing expert information and answering questions.
      Husbands, friends, or family were important resources for closest personal facets
      of breastfeeding, including encouraging confidence. At two weeks postpartum,
      breastfeeding mothers had larger total support scores than non-breastfeeding
      mothers. USNQ reliably discriminated between professional and personal support
      for breastfeeding.

PMID- 8260056
TI  - Codeine and the breastfed neonate.
AB  - Codeine is an analgesic commonly used to relieve pain in the early post partum.
      Its metabolite, morphine, is probably responsible for its effectiveness in this
      use. However, morphine may also cause neonatal apnea. We studied free codeine and
      morphine levels in breastmilk of 17 samples from seven mothers and neonatal
      plasma of 24 samples from 11 healthy, term neonates. Levels were determined by
      radioimmunoassay. Milk codeine levels ranged from 33.8 to 314 ng/ml 20 to 240
      minutes after codeine; morphine levels ranged from 1.9 to 20.5 ng/ml. Infant
      plasma samples one to four hours after feeding had codeine levels ranging from <
      0.8 to 4.5 ng/ml; morphine ranged from < 0.5 to 2.2 ng/ml. Low infant plasma
      levels are secondary to low excretion into milk and the small amounts of milk
      available in the first few days. Moderate codeine use during this time (< or =
      four 60 mg doses) is probably safe.

PMID- 8260057
TI  - Skin-to-skin contact beginning in the delivery room for Colombian mothers and
      their preterm infants.
AB  - To determine if the transition to extrauterine life is facilitated by skin-to
      skin contact, six relatively low risk preterm infants experienced six continuous
      hours of skin-to-skin contact on their mothers' chests beginning within 30
      minutes of birth. Heart and respiratory rates and oxygen saturation remained
      within normal limits and all infant temperatures rose rapidly to thermoneutral
      range. Two infants developed grunting respirations by the time skin-to-skin
      contact began, but the grunting disappeared with warm, humidified oxygen and
      continuous skin-to-skin contact. All infants were fully breastfeeding and ready
      for discharge by 24-48 hours postbirth. Early skin-to-skin contact was safe and
      seemed beneficial for these relatively low risk preterm infants.

PMID- 8260058
TI  - Assessments and suggested interventions to assist newborn breastfeeding behavior.
AB  - Assessment of the newborn infant in the first few days after birth is important
      to ensure that the newborn and mother are beginning to establish lactation
      successfully. This article discusses breastfeeding assessment of the healthy
      neonate and includes a description of the Infant Breastfeeding Assessment Tool
      (IBFAT), a checklist on which neonatal breastfeeding behavior can be scored. Some
      interventions are suggested for those babies who may be having difficulties.

PMID- 8260059
TI  - Can magnesium sulfate therapy impact lactogenesis?
AB  - This case report describes a patient who ingested magnesium sulfate (MgSO4) for
      approximately four days as a treatment for pregnancy-induced hypertension. Stage
      II lactogenesis was delayed until the tenth postpartum day at which point the
      patient's breasts became fully engorged. No explanation for this delay was found,
      other than the possibility that magnesium sulfate treatment impeded lactogenesis.
      Implications for professionals who care for lactating women are discussed.

PMID- 8260060
TI  - In-service breastfeeding program development: needs assessment and planning.
AB  - In-service program development requires that the individual offering it be
      familiar with needs assessment techniques and program planning. In order to
      provide a program appropriate to the audience's needs, the presenter needs first
      to identify and set goals for the program, identify objectives relevant to the
      participants' needs, outline the material to be presented, and select the most
      appropriate presentation methodologies and ways of evaluating the program. This
      discussion includes examples and sample assessment forms that are specific to a
      breastfeeding program.

PMID- 8260061
TI  - Infant feeding preference card.

PMID- 8260062
TI  - Use of donor breastmilk in the nutrition management of chronic renal failure:
      three case histories.

PMID- 8260063
TI  - Feminology: a guide for womankind, giving in detail instructions as to
      motherhood, maidenhood, and the nursery. 1906.

PMID- 8260064
TI  - 1993 task analysis and role delineation study.

PMID- 8260065
TI  - The joys and challenges of promoting breastfeeding in south central Los Angeles.

PMID- 8260066
TI  - A summary of 1992 ILCA membership surveys.

PMID- 8260067
TI  - Mechanisms of carcinogenicity of methyl halides.
AB  - Methyl chloride, bromide, and iodide are used as methylating agents. These
      compounds are mutagenic in short-term tests and do not require activation by
      exogenous S9 mix. In DNA-binding studies performed in rats and mice, 14C-labeled
      methyl chloride was given by inhalation, and methylation of DNA bases was
      examined. The compound did not lead to specific DNA adducts. In particular,
      methylation of DNA bases was not observed. In contrast, methyl bromide and methyl
      iodide, upon oral and inhalation administration to rats and mice, caused systemic
      DNA methylation. Specifically, 3-methyl-adenine, 7-methyl-guanine, and O6-methyl
      guanine were formed. Long-term inhalation bioassays have been performed in rats
      and mice with methyl chloride and methyl bromide. Methyl chloride induced renal
      tumors, but only in male mice at the highest concentration tested (1000 ppm).
      Under these special conditions, a number of secondary effects occur subsequent to
      glutathione depletion in the target tissue, resulting in DNA damage (DNA-protein
      cross-links and probably DNA single-strand breaks). The particular coincidence of
      secondary high-dose effects precludes a risk extrapolation to man. Methyl bromide
      did not induce tumors in rats and mice when administered by inhalation. However,
      experimental data point to a possible local carcinogenic effect on the rat
      forestomach when the compound is given by gavage. A factor that accounts for the
      discrepancy between systemic DNA methylation and apparent noncarcinogenicity upon
      inhalation might be the preference of 7-N over O6 methylation of guanine. An
      extrapolation of the negative rodent inhalation bioassay of methyl bromide to man
      might be problematic because rodents metabolize methyl bromide very quickly
      whereas in humans there is a particular subpopulation that only poorly
      metabolizes the compound ("nonconjugators"). Such individuals can be
      characterized by incubation of erythrocytes with methyl chloride or methyl
      bromide and measurement of the substrate decline. Methyl iodide has been tested,
      with positive outcome, in early carcinogenicity bioassays not based on modern
      methodology. However, these results, along with the proven systemic methylating
      potency of methyl iodide, argue in favor of a carcinogenic effect of the
      compound.

PMID- 8260068
TI  - Mechanisms of chromium carcinogenicity and toxicity.
AB  - Chromium, like many transition metal elements, is essential to life at low
      concentrations yet toxic to many systems at higher concentrations. In addition to
      the overt symptoms of acute chromium toxicity, delayed manifestations of chromium
      exposure become apparent by subsequent increases in the incidence of various
      human cancers. Chromium is widely used in numerous industrial processes, and as a
      result is a contaminant of many environmental systems. Chromium, in its myriad
      chemical forms and oxidation states, has been well studied in terms of its
      general chemistry and its interactions with biological molecules. However, the
      precise mechanisms by which chromium is both an essential metal and a carcinogen
      are not yet fully clear. The following review does not seek to embellish upon the
      proposed mechanisms of the toxic and carcinogenic actions of chromium, but rather
      provides a comprehensive review of these theories. The chemical nature of
      chromium compounds and how these properties impact upon the interactions of
      chromium with cellular and genetic targets, including animal and human hosts, are
      discussed.

PMID- 8260069
TI  - Developmental and reproductive toxicity of dioxins and related compounds: cross
      species comparisons.
AB  - Developmental toxicity to TCDD-like congeners in fish, birds, and mammals, and
      reproductive toxicity in mammals are reviewed. In fish and bird species, the
      developmental lesions observed are species dependent, but any given species
      responds similarly to different TCDD-like congeners. Developmental toxicity in
      fish resembles "blue sac disease," whereas structural malformations can occur in
      at least one bird species. In mammals, developmental toxicity includes decreased
      growth, structural malformations, functional alterations, and prenatal mortality.
      At relatively low exposure levels, structural malformations are not common in
      mammalian species. In contrast, functional alterations are the most sensitive
      signs of developmental toxicity. These include effects on the male reproductive
      system and male reproductive behavior in rats, and neurobehavioral effects in
      monkeys. Human infants exposed during the Yusho and Yu-Cheng episodes, and
      monkeys and mice exposed perinatally to TCDD developed an ectodermal dysplasia
      syndrome that includes toxicity to the skin and teeth. Toxicity to the central
      nervous system in monkey and human infants is a potential part of the ectodermal
      dysplasia syndrome. Decreases in spermatogenesis and the ability to conceive and
      carry a pregnancy to term are the most sensitive signs of reproductive toxicity
      in male and female mammals, respectively.

PMID- 8260070
TI  - Human exposure to 2,3,7,8-TCDD and risk of cancer--a response.

PMID- 8260071
TI  - Sampling conditions for biological fluids for trace elements monitoring in
      hospital patients: a critical approach.
AB  - Lack of coherence in the results of trace element (TE) analyses produced by
      various laboratories has been such as to necessitate much needed technical
      improvements and more detailed control over sample preparations. For too long,
      except for a few praiseworthy researchers, the importance of sampling conditions
      has been underestimated as a source of erroneous TE results. Many of the
      precautionary procedures for previously studied TE collection materials have
      proven to be so cumbersome that they cannot be applied in a hospital setting.
      This report deals with sampling material and conditions from a workday
      standpoint; a rigorous description of the contaminating roles of ambient air and
      routine handling of specimens places emphasis on the practical. While some
      metals, including cobalt, copper, iron, and selenium, present no significant risk
      of contamination, others, such as aluminum, cadmium, chromium, manganese, and
      nickel, pose quite a significant risk. They warrant attention with respect not
      only to the sampling itself but also the selection of the material to be used.
      Drawing on our hospital experience, we propose a critical approach toward the
      collection of samples of biological fluids (blood, urine, dialysis fluids).
      Needles, catheters, tubes (open and evacuated systems), and anticoagulants on the
      market are likewise assessed in terms of their contaminative roles. For each one
      elementary rules as well as realistic choices of materials and methods for a
      hospital environment are proposed.

PMID- 8260072
TI  - Protein and amino acid metabolism in cancer cachexia: investigative techniques
      and therapeutic interventions.
AB  - Cancer cachexia is a complex syndrome characterized primarily by diminished
      nutrient intake and progressive tissue depletion that is manifest clinically as
      anorexia and host weight loss. The gradual loss of host protein stores is central
      to this process. This review outlines the techniques that have been used to
      evaluate human amino acid metabolism, their application in patients with cancer
      cachexia, and possible therapeutic interventions designed to overcome alterations
      in host protein and amino acid metabolism associated with malignant cachexia. The
      techniques of nitrogen balance and 3-methylhistidine excretion provide indirect
      estimates of overall nitrogen metabolism and skeletal muscle myofibrillar protein
      breakdown. Measurement of circulating amino acid concentrations, particularly
      when combined with assessment of arterial-venous differences and regional amino
      acid balance allows for investigation of interorgan amino acid metabolism. One of
      the most significant advances in in vivo amino acid metabolic research has been
      the development of labeled amino acid tracer studies to evaluate whole body and
      regional amino acid kinetics. The use of stable and unstable amino acid isotopes
      in these techniques is reviewed in detail. Virtually all of these techniques have
      now been employed in the evaluation of human cancer cachexia. The results of
      studies evaluating amino acid concentrations, regional amino acid balance, and 3
      methylhistidine excretion are summarized. The use of regional and whole body
      kinetic studies in cancer cachexia are reviewed extensively. Most investigators
      have observed increased rates of whole body protein turnover, synthesis, and
      catabolism in both weight-stable and weight-losing cancer patients. Some studies
      have suggested a relationship between the extent of disease and the degree of
      aberration in amino acid kinetic parameters. Investigators have attempted to
      reverse some of these alterations by provision of substrate (nutritional support)
      or administration of specific pharmacologic or anabolic agents such as hydrazine
      sulfate, insulin, growth hormone, and beta-2 agonists. The role of total
      parenteral nutrition (TPN) in cancer and its effects on protein and amino acid
      kinetics and tumor growth are addressed. The possible benefits of specific amino
      acid nutritional formulations with increased branched chain amino acids,
      arginine, and glutamine are reviewed. Although many of these approaches appear
      promising, significant impact on clinically definable parameters remains to be
      demonstrated. A better understanding of the underlying protein catabolic
      mechanisms of cancer cachexia will likely lead to more effective therapies to
      reverse the protein calorie malnutrition associated with cancer cachexia.

PMID- 8260073
TI  - Pepsinogens in health and disease.
AB  - Pepsinogens, precursors of pepsins (potent and abundant digestive enzymes that
      are the primary products of the gastric chief cells), are members of the family
      of aspartic proteases. Because of the heterogeneity of pepsinogens, several
      classifications have appeared in the literature. I describe the recommended
      classification and nomenclature of the aspartic proteases and discuss their
      genetics, biochemistry (structure, activation of zymogens, mechanism of
      proteolytic activity and inhibitors), and physiology. The focus will be on the
      zymogens of pepsin, the so-called pepsinogens. The measurement of these enzymes
      in serum is a reliable noninvasive biochemical method for evaluating peptic
      secretion and obtaining information on the gastric mucosal status. A detailed
      review of the methods for the measurement of pepsinogens in serum, urine, and
      gastric mucosa is also provided. Data on pepsinogen levels in healthy subjects
      are discussed with respect to sex, age, smoking habit, and the presence of a
      circadian rhythm. The value of pepsinogen measurements in peptic ulcer to
      determine ulcer outcome and recurrence, in gastric cancer, and in Helicobacter
      pylori infection is reviewed. Finally, the effects of drugs on peptic secretion
      are discussed. In light of these data, the measurement of aspartic proteases, and
      in particular that of pepsinogen A and C, may be regarded as an effective
      biochemical approach to the evaluation and monitoring of patients with upper
      gastrointestinal diseases.

PMID- 8260074
TI  - Carbohydrate metabolism in fetuses with Rh alloimmunization.
AB  - Glucose, insulin, glucagon and fructosamine were measured in the plasma of
      control (n = 34) and of Rh fetuses (n = 22) before the first and subsequent
      transfusion. Prior to treatment, Rh fetuses, compared to controls, had raised
      concentrations of glucose (p = 0.01), glucagon (p = 0.04) and fructosamine (p =
      0.004). Fetal insulin levels were not significantly different. Before subsequent
      transfusion, despite correction of anemia, Rh fetuses were clearly
      hyperinsulinemic even after correction for gestation (p = 0.002) and had low
      glucagon concentrations (p = 0.01) when compared with values at the first
      transfusion. This metabolic milieu appears similar to that of fetuses of diabetic
      mothers which have increased plasma glucose and insulin during most of the last
      third of gestation.

PMID- 8260075
TI  - Fetal plasma tumor necrosis factor concentration in normal pregnancy.
AB  - The aim of the study was to investigate changes with gestation of fetal plasma
      tumor necrosis factor alpha (TNF-alpha) concentration. In a cross-sectional
      study, enzyme-linked immunoassay was used to measure plasma TNF-alpha
      concentration in 40 fetal blood samples obtained by cordocentesis (n = 25),
      cardiocentesis (n = 5) or at elective caesarean section (n = 10) at 12-38 weeks
      gestation. The fetal plasma concentration of TNF-alpha increased from a mean of
      13.5 pg/ml at 12 weeks gestation to 37.5 pg/ml at 38 weeks (r = 0.59, p <
      0.0001), and was significantly associated with the monocyte count (r = 0.56, p <
      0.001). TNF-alpha is present in the fetal circulation from at least 12 weeks and
      the changes in plasma TNF-alpha concentration with gestation coincide with the
      development of the fetal monocyte-macrophage system.

PMID- 8260076
TI  - Prediction of fetal distress and poor outcome in intrauterine growth retardation-
      a comparison of fetal heart rate monitoring combined with stress tests and
      Doppler ultrasound.
AB  - One hundred and three intrauterine growth retardation (IUGR) pregnancies were
      scheduled for pulsed Doppler ultrasound of the common carotid and the umbilical
      artery, nonstress and contraction stress tests (NST/CST) as well as vibroacoustic
      stimulation tests (VAST). The last examinations < 3 days before birth were
      compared by receiver-operator characteristics: Results of the resistance indices
      of fetal common carotid/umbilical artery and NST were more predictive of later
      fetal distress during labour, compared to CST and VAST (p < 0.001/< 0.01).
      Similar results were found for the prediction of low pH and Apgar values, though
      differences were less pronounced. Our results suggest that stressful examinations
      should be abolished from mother and fetus in the supervision of IUGR.

PMID- 8260077
TI  - Ultrasonic prediction of discordant growth in twin pregnancies.
AB  - In this prospective study conducted from 1984 through 1987, the ability to
      correctly predict growth discordancy in twin gestations by ultrasonic estimated
      fetal weights is examined. Discordancy was defined as an intertwin birth weight
      difference of 25% or greater. This method resulted in a sensitivity rate of 77%
      and a specificity rate of 92%. The positive predictive value of an abnormal test
      (i.e. discordant growth) was 67% and the negative predictive value of a normal
      test (i.e. concordant growth) was 95%. The perinatal mortality rate of 217/1,000
      in discordant twin fetuses was significantly higher than 29/1,000 in the
      concordant twins in this study population (p < 0.01) and even more of a contrast
      to the rate of 10/1,000 in our singleton population. Accurate prediction of
      discordant twin pregnancies which are at high risk for poor outcome opens the
      opportunity for potential in utero treatment modalities.

PMID- 8260078
TI  - Clinical use of Doppler ultrasound in pregnancy: information from six randomised
      trials.
AB  - The objective of this report was to undertake an overview of the clinical utility
      of umbilical Doppler ultrasound in the management of high-risk pregnancies. The
      study is designed as a formal meta-analysis of 6 randomised trial reports
      selected by predetermined criteria and was performed at the Division of
      Reproductive Medicine, Newcastle University, Australia. A total of 6 randomised
      controlled trials amounted to 2,102 patients in the experimental (Doppler) group
      and 2,133 patients in the control group. All patients had high-risk pregnancies.
      The management of pregnancies with Doppler was compared to those with standard
      obstetric management (i.e. excluding Doppler). Main outcome measures were
      perinatal mortality in the form of intrauterine deaths as well as obstetric
      performance indicators including caesarean section, elective delivery, fetal
      distress in labour, antenatal admissions and admissions to Neonatal Intensive
      Care Unit. The meta-analysis shows a significant reduction in perinatal mortality
      in the groups in which Doppler was used. Typical odds ratio was 0.5 [95%
      confidence intervals (CI) 0.34, 0.73]. The specific reduction in perinatal
      mortality occurred in intrauterine deaths in otherwise normally formed fetuses.
      The typical odds ratio was 0.54 with 95% CI 0.32, 0.89. This meta-analysis shows
      a significant reduction in overall perinatal mortality, specifically in the form
      of intrauterine deaths in otherwise normally formed babies.

PMID- 8260079
TI  - Subjective ultrasonographic assessment of amniotic fluid depth: comparison with
      the amniotic fluid index.
AB  - The purpose of this study was to evaluate the ability to identify abnormalities
      in amniotic fluid volume by subjective ultrasonographic assessment compared to a
      semiobjective method. In 886 consecutive ultrasound examinations subjective
      assessment of the amniotic fluid volume was performed and graded into 3
      categories: normal, decreased, and increased. Following that, a four-quadrant sum
      (amniotic fluid index) was performed by the same experienced ultrasonographer and
      divided into 3 categories using the 5th and 95th percentiles. The sensitivity of
      the subjective analysis to diagnose a decreased amniotic fluid volume when
      compared with the amniotic fluid index was 58% (95% confidence interval, CI: 40
      70%), with a false-positive rate of 17% (CI 8-32%). The sensitivity of the
      subjective analysis to diagnose an increased amniotic fluid volume when compared
      with the amniotic fluid index was 100% (CI 70-100%). However, the false-positive
      rate was 74% (CI 55-85%). Diagnosis of a normal amount of amniotic fluid by the
      subjective technique had a sensitivity of 96% (CI 95-97%) and a false-positive
      rate of 3% (CI 2-4%). Subjective ultrasonographic assessment of the amniotic
      fluid volume may serve as a screening test for the experienced ultrasonographer.
      However, when a decreased or increased amount of amniotic fluid volume is
      suspected, one may elect to use the amniotic fluid index for confirmation of the
      subjective impression.

PMID- 8260080
TI  - Ultrasonographic prenatal diagnosis of the 13q-syndrome.
AB  - A case is presented in which ultrasonographic examination led to the prenatal
      detection of a ring 13 chromosome in a fetus. At 18 weeks' gestation, the fetus
      presented with holoprosencephaly, an abnormal configuration of the lower
      extremities, and an atrial septal defect. Although the amount of amniotic fluid
      was normal, limb movements were never observed throughout pregnancy. The lower
      extremities were always flexed at the knee and talipes equinovarus was present.
      Hydrocephaly became apparent during the 2nd trimester. The ultrasonographic
      findings were confirmed by postpartum autopsy and X-ray examination. The ring
      chromosome was identified through amniocentesis and later verified in postpartum
      tissue.

PMID- 8260081
TI  - A large unilateral contained urinoma in a fetus: an indication for intrauterine
      urinary shunting.
AB  - A large contained urinoma measuring 12 x 8 x 8 cm3 was diagnosed in the left
      kidney of a female fetus at 28 weeks gestation. Analysis of fluid from serial
      punctures of the cyst indicated that renal function on that side was poor, but
      because ultrasound findings of the thorax suggested lung growth impairment, a
      shunt was inserted. After 3 weeks the shunt dislocated into the fetal abdominal
      cavity and urinous ascites developed. The ascites was found to have resolved
      spontaneously on ultrasonography 3 weeks later. The infant was delivered at 37
      weeks gestation and appeared normal except for bilateral pelvi-ureteric
      obstruction. This was much worse in the left kidney, the renal function of which
      was only 10% of normal. A left nephrectomy was carried out when the infant was 6
      months old, when the inner part of the shunt was discovered in perinephric
      fibrous tissue. The renal pelvis was greatly enlarged and fibrotic; no site of
      rupture could be identified. The infant's respiratory function was normal. This
      case suggests the use of intrauterine shunting to decompress a large unilateral
      urinoma resulting in marked elevation of the fetal diaphragm to prevent
      impairment of fetal lung growth.

PMID- 8260082
TI  - Neonatal hemochromatosis: a rare cause of nonimmune hydrops fetalis and fetal
      anemia.
AB  - Neonatal hemochromatosis is a rare inherited disorder of iron metabolism in which
      various tissues contain excessive amounts of iron. Only in a very few cases in
      which the disease is associated with fetal nonimmune hydrops is there the
      possibility for prenatal diagnosis. We present a case of fetal nonimmune hydrops
      fetalis in which severe fetal anemia and elevated liver enzymes were found.
      Retrospectively, according to pathological examination, these were signs of
      neonatal hemochromatosis. Only the knowledge of the disease entity allows
      antenatal diagnosis and rational perinatal management.

PMID- 8260083
TI  - Bilateral renal agenesis and cytomegalovirus infection in a case of Fraser
      syndrome.
AB  - A case of Fraser syndrome diagnosed prenatally is presented. Detection of
      oligohydramnios, hydrops fetalis and bilateral absence of the kidneys were the
      initial findings leading to further study. Specific IgM for cytomegalovirus in
      maternal serum and confirmed infection by fetal blood sampling was an associated
      finding. The importance of an etiologic diagnosis of nonimmune hydrops and the
      relevant aspects of genetic counselling are emphasized. The association of the
      Fraser syndrome with cytomegalovirus infection has not been previously reported.

PMID- 8260084
TI  - Peptide presentation by major histocompatibility class I molecules.

PMID- 8260085
TI  - MHC class I-restricted antigen processing--lessons from natural ligands.

PMID- 8260086
TI  - Studies on naturally processed peptides associated with MHC class II molecules.

PMID- 8260087
TI  - Isolation and characterization of naturally processed peptides bound by class II
      molecules and peptides presented by normal and mutant antigen-presenting cells.

PMID- 8260088
TI  - The dichotomy of peptide presentation by class I and class II MHC proteins.

PMID- 8260089
TI  - Mass spectrometric analysis of peptides associated with the human class I MHC
      molecules HLA-A2.1 and HLA-B7 and identification of structural features that
      determine binding.

PMID- 8260090
TI  - Interactions between peptides and major histocompatibility complex molecules
      during antigen processing and presentation.

PMID- 8260091
TI  - Tissue-specific expression of self peptides bound by major histocompatibility
      complex class II molecules.

PMID- 8260092
TI  - [Incontinence].

PMID- 8260093
TI  - [Care for incontinence in community health care. An oriented anamnesis. Interview
      by Corina de Feijter and Tonny van de Pasch].

PMID- 8260094
TI  - [Outpatient clinic. Incontinence. Interview by Corina de Feijter and  Tonny van
      de Pasch].

PMID- 8260095
TI  - [Functional incontinence].

PMID- 8260096
TI  - [Urodynamic studies. Interview by Corina de Feijter and Tonny van de Pasch].

PMID- 8260098
TI  - [A standard nursing plan. Interview by Tonny van de Pasch].

PMID- 8260097
TI  - [A skirt on Sunday?].

PMID- 8260099
TI  - [In the AZG (Academic Hospital Groningen) a lot of attention for social problems
      in incontinence. Interview by Corina de Feijter].

PMID- 8260100
TI  - [Often you really can do something about it. Incontinence in psychiatry.
      Interview by Corina de Feijter].

PMID- 8260101
TI  - [Handicapped and incontinent. Interview by Corina de Feijter].

PMID- 8260102
TI  - [Incontinence problems in subjects with a physical disability. Nursing care].

PMID- 8260103
TI  - [Aids in incontinence].

PMID- 8260104
TI  - [Who pays for/determines incontinence materials?].

PMID- 8260105
TI  - [The 10th ISQA Conference: an interview. 'The Dutch are more creative and more
      enthusiastic' (International Society for Quality Assurance)].

PMID- 8260106
TI  - [Legal regulation of intensive care education. New regulation in the sign of
      'deregulation'].

PMID- 8260107
TI  - [Nursing sciences in Utrecht. Preparation, realization and a look into the
      future].

PMID- 8260108
TI  - [Absenteeism].

PMID- 8260109
TI  - [Handling cytostatic agents--are the new guidelines effective?].

PMID- 8260110
TI  - [Management of unstructured problems. Intermediate management training should be
      better attuned to the 'reverse side' of organizations].

PMID- 8260111
TI  - [Marketing and quality].

PMID- 8260112
TI  - [Mentally handicapped with self mutilating behavior. Starting points for
      treatment and daily care].

PMID- 8260113
TI  - [Jurisprudence establishes guidelines for professional nursing activities.
      Interview with the compilers of 'Nurses in Court'].

PMID- 8260114
TI  - [5 years nursing science in Groningen. Study facilities of employer appear to be
      crucial].

PMID- 8260115
TI  - [Nurse scientists give new content to existing functions. Theo Dassen on
      'Groningen'. Interview by Tonny van de Pasch].

PMID- 8260116
TI  - [Winti: background and significance].

PMID- 8260118
TI  - Continuous versus intermittent sulphonylurea therapy in non-insulin-dependent
      diabetes mellitus.
AB  - Although it is 50 years since the discovery of the hypoglycaemic effects of
      sulphonylureas, the molecular basis of their effects are still not fully
      understood. It has been suggested that long term sulphonylurea therapy may
      desensitise the pancreatic beta-cells to further drug effects, and that
      intermittent sulphonylurea therapy may be the best approach to maintain their
      effectiveness. A randomised, double-blind study has been carried out to attempt
      to answer the question of whether intermittent sulphonylurea therapy is more
      effective then continuous administration. Responders to oral glibenclamide
      (glyburide) went on to receive continuous or intermittent treatment
      (glibenclamide for 2 weeks then placebo for 2 weeks) for 16 weeks. Glycaemic
      control was maintained in the continuous treatment group. However, glucose levels
      deteriorated in the intermittent treatment group, suggesting that there is no
      merit to intermittent sulphonylurea treatment. Other strategies to investigate
      include administration on an alternate-day basis or a shorter period off the drug
      (e.g. 1 week). The underlying question of optimal glycaemic control with
      sulphonylureas warrants a definitive answer.

PMID- 8260117
TI  - Calcium antagonists. A role in the management of cyanide poisoning?

PMID- 8260119
TI  - Adverse effects of intravenous immunoglobulin.
AB  - The range of diseases in which intravenous immunoglobulin (IVIG) is effective has
      expanded significantly since its initial use in primary antibody deficiency.
      There are at present at least 17 preparations of IVIG in use worldwide with
      similar profiles of adverse effects. Infusion-related effects range in severity.
      Mild adverse reactions (headache, flushing, low backache, nausea, wheezing) are
      often associated with a fast infusion rate, and respond rapidly on slowing the
      infusion. Very rare episodes of life-threatening anaphylaxis may occur,
      particularly in those IgA-deficient patients with anti-IgA antibodies; such
      patients should receive an IgA-depleted preparation of IVIG. There are concerns
      with any blood product about safety in regard to viral transmission. The 4
      outbreaks of non-A non-B hepatitis (probably hepatitis C) in the 1980s were
      associated with the use of particular batches of IVIG. The more recent exclusion
      of all anti-hepatitis C virus positive individuals from the donor pool, and the
      introduction of specific antiviral steps in the manufacture of IVIGs, should
      prevent further outbreaks. The human immunodeficiency virus (HIV) is effectively
      inactivated during the manufacturing process itself and HIV transmission has not
      been reported with IVIG. Rarely, haematological (Coombs' test positive
      haemolysis), neurological (aseptic meningitis) or renal (transient rises in serum
      creatinine) adverse effects may be seen when high doses of IVIG are used for
      immunomodulatory purposes. Haemolysis, due to passive transmission of blood group
      antibodies (anti-A, anti-D), may be prevented by selecting IVIG batches that give
      a negative cross-match between the recipient's red cells and IVIG.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260120
TI  - Adverse effects of coumarin anticoagulants.
AB  - The biochemistry of vitamin K metabolism and the role of vitamin K-dependent
      gamma-carboxylation of the vitamin K-dependent coagulation factors are now well
      understood. Likewise, there is a clear understanding of the role of oral
      anticoagulants in the inhibition of these coagulation factors. However, the
      effect of oral anticoagulants on extrahepatic gamma-carboxylated proteins such as
      osteocalcin and matrix gamma-carboxyglutamate (Gla)-protein (MGP), and the
      effects of long term anticoagulants on bone mineral metabolism are just now being
      recognised. The relevance of these observations on mineral metabolism for elderly
      individuals, and in particular postmenopausal women who are on long term
      anticoagulants, is still unknown but worthy of continued close observation. The
      most significant hazard of oral anticoagulants is haemorrhage. Clinical trials
      continue to demonstrate that less intense (lower dosage) warfarin therapy can
      significantly decrease this risk of haemorrhage while at the same time providing
      equal efficacy when compared to more intense warfarin therapy. The more
      widespread use of the International Normalised Ratio (INR) for the control of
      anticoagulants will undoubtedly further decrease the risk of haemorrhage, but new
      innovations such as the use of ultra low-dose warfarin or newer techniques for
      the continued monitoring of oral anticoagulants are still required, particularly
      as the indications for oral anticoagulants continue to expand.

PMID- 8260121
TI  - Adverse reactions to oral retinoids. An update.
AB  - Retinoids, both naturally occurring and synthetic, are analogues of vitamin A.
      They represent a major advance in the treatment of acne and psoriasis, as well as
      rarer conditions such as the ichthyoses. The more frequent and widespread use of
      these drugs requires that the dermatologist be aware of the wide spectrum of
      adverse events that may be encountered with their use. Some are serious and
      irreversible, such as teratogenicity, necessitating great care if these drugs are
      given to women of childbearing potential. Other effects may be less severe, dose
      dependent and reversible. Although not devastating to the patient, appropriate
      advice may reduce morbidity.

PMID- 8260123
TI  - Possible interaction between phenobarbital, carbamazepine and itraconazole.
AB  - We report a case of a possible interaction between itraconazole, phenobarbital
      and carbamazepine. The first plasma itraconazole concentration, measured when the
      patient had been taking phenobarbital for 2 months, was very low. The second
      measurement, 2 months after withdrawing phenobarbital, was higher but below the
      therapeutic range. However, carbamazepine, a well known enzyme inducer, had been
      initiated 15 days before. 20 days after carbamazepine was withdrawn, the
      itraconazole concentration 4 hours after administration was near the lower end of
      the therapeutic range. The mechanism of this possible interaction is probably the
      same for phenobarbital and carbamazepine, involving hepatic microsomal enzyme
      system induction.

PMID- 8260122
TI  - Epidemiology of drug overdose in children.
AB  - Childhood drug overdoses are a continuing important public health problem.
      Although drug overdoses are no longer the important cause of childhood mortality
      they once were, such poisonings account for highly frequent and unacceptable
      instances of childhood injuries. These poisonings exact a high cost from society.
      They result in many emergency department visits and hospitalisations, with the
      attendant indirect costs of suffering, parental anxiety, and lost days of work or
      school. Childhood drug overdoses are preventable; those children and families at
      highest risk show identifiable characteristics, and the medications which pose
      the greatest hazard to children have already been identified. These injuries
      divert expensive and scarce medical resources from society's other health
      problems. Thus, clinicians must do more to prevent childhood drug overdoses
      whenever possible.

PMID- 8260125
TI  - Issues concerning medical school admission for students with disabilities.

PMID- 8260124
TI  - Effects of zolpidem, codeine phosphate and placebo on respiration. A double
      blind, crossover study in volunteers.
AB  - The effects of zolpidem, codeine phosphate and placebo on respiration were
      evaluated in a double-blind, randomised, crossover study involving 12 healthy
      men. Single oral doses of zolpidem 10 or 20 mg, codeine phosphate 60 mg or
      placebo were administered in the morning. Each treatment was separated by a
      washout period of at least 72 h. Ventilatory responses to carbon dioxide and
      mouth occlusion pressure, measured 1 h before and at 1 and 3 h after doses, were
      not significantly affected by either zolpidem dose; however, codeine phosphate
      produced a small but significant respiratory suppressant effect at 3 h. Mean
      inspiratory flow was noninvasively assessed using respiratory inductive
      plethysmography 1 h predose and at 1 to 5 h postdose. No significant change in
      mean inspiratory flow was noted after zolpidem 10 mg. Two hours after
      administration of zolpidem 20 mg, mean inspiratory flow was significantly lower
      than after placebo, possibly related to some individuals falling asleep during
      data collection. All volunteers reported adverse events; the most common were
      slurred speech (in 1 after 10 mg and in 5 after 20 mg of zolpidem), dizziness (in
      4 after both 10 mg and 20 mg of zolpidem) and diplopia/blurred vision (in 4 after
      20 mg of zolpidem). Zolpidem appears to be well tolerated, with no respiratory
      suppression up to doses of 10 mg and minimal suppression of mean inspiratory
      drive at doses of 20 mg.

PMID- 8260126
TI  - Amyotrophic lateral sclerosis. Communication status and survival with ventilatory
      support.
AB  - The use of ventilatory support via an indwelling tracheostomy tube in the
      management of advanced amyotrophic lateral sclerosis patients demands the
      commitment of enormous resources. The use of noninvasive respiratory aids can
      facilitate and simplify home management, decrease expense and prepare patients
      and families for decision making regarding tracheostomy if and when this becomes
      necessary. The purposes of this study were to: describe the utility of
      noninvasive respiratory aids, determine to what extent survival might be expected
      to increase by the use of mechanical ventilation, and explore the consequences of
      patient disposition and communication status on survival. Eighty-nine patients
      survived a mean of 4.4 +/- 3.9 yr (range = 1 month to 26.5 yr) using respiratory
      support. This included 37 patients who were still alive. The up to 24 h use of
      noninvasive intermittent positive pressure ventilation (IPPV) methods delayed or
      eliminated tracheostomy for 25 patients. Survival was comparable for patients
      maintained at home or in chronic care facilities. The maintenance of effective
      communication appeared to favor patients remaining in the community. It could not
      be shown to affect survival, but it greatly increased quality of life. The use of
      noninvasive respiratory muscle aids can eliminate the need for "crisis" decision
      making regarding tracheostomy for many individuals with ALS.

PMID- 8260127
TI  - Effect of age on progression through temporary prostheses after below-knee
      amputation.
AB  - Forty six patients that underwent below knee amputation for diabetes,
      trauma/osteomyelitis or peripheral vascular disease were studied. Healing was
      estimated by the rate of progression through temporary prostheses as determined
      weekly by the amputee rehabilitation team (physiatrist, orthopedist, physical
      therapist, nurse, and prosthetist). For all groups combined, mean days +/-
      standard error from amputation to above knee cast with pylon and foot (AKPy) were
      22.9 +/- 1.9, to below knee cast with pylon and foot (BKPy) 41.6 +/- 2.8 and to
      laminated temporary prostheses 66.5 +/- 4.5. A regression analysis of these
      variables on age (range: 29 to 84 yr) showed significant positive correlations
      for AKPy (r = 0.34, P = 0.0214) and BKPy (r = 0.40, P = 0.0056). An analysis of
      variance with contrasts (Tukey's protected t) showed significant lower values (P
      < 0.05) for amputation to BKPy in the trauma/osteomyelitis group when compared to
      diabetes or peripheral vascular disease and no difference among the last two
      groups. However, when variables were adjusted for age (analysis of covariance
      with age as a covariate), the differences among groups disappeared (covariance
      F(2,44) = 0.9, P > 0.4). In conclusion, age, not the cause of the amputation,
      correlated with healing after below knee amputation as estimated by the rate of
      progression through temporary prostheses.

PMID- 8260128
TI  - Return to work for persons following severe traumatic brain injury. Supported
      employment outcomes after five years.
AB  - Supported employment is a recently developed rehabilitation alternative that is
      being used to assist individuals with traumatic brain injury to return to work.
      The present study reports the results of a supported employment program that has
      placed 80 individuals into competitive employment during a 5-year time period.
      All individuals had sustained a severe traumatic brain injury; 72% of the
      injuries involved a motor vehicle. A mean of 6.1 years had passed since injury
      for all participants, who had been unconscious an average of 48 days.
      Neuropsychologic evaluation revealed defective cognitive functioning, which
      contributed to diminished employment potential. A key outcome indicator used to
      assess return to work capacity is the monthly employment ratio, which is computed
      by dividing the number of months employed during an employment phase (i.e.,
      pre/post injury) by the total possible months an individual would have the
      opportunity to be employed. The monthly employment ratio increased from 13% after
      injury with no supported employment to 67% with supported employment services.
      The majority of individuals were employed in warehouse, clerical and service
      related occupations. A mean of 250 staff intervention hours were required to
      train and provide follow-up services to program participants.

PMID- 8260129
TI  - Botulinum toxin for the treatment of spasticity in multiple sclerosis. New
      observations.
AB  - Potential advantages of intramuscular botulinum toxin for the treatment of
      spasticity include the lack of sensory effects, ability to target specific muscle
      groups, ability to weaken muscles in a graded fashion and absence of caustic
      chemicals such as phenol. We describe the use of botulinum toxin for the
      treatment of severe lower extremity spasticity in two subjects with multiple
      sclerosis. Both subjects showed an improvement in spasticity, as measured by the
      modified Ashworth scale, and in functional status. Both subjects exhibited
      reductions in muscle tone not only in injected muscles, but also in noninjected
      muscles in the region. These more distant clinical effects have not been
      emphasized in previous studies after therapeutic injections of botulinum toxin.
      Further research is needed to clarify the cause and prevalence of these regional
      motor effects, as well as to further examine the safety and efficacy of botulinum
      toxin for spasticity treatment.

PMID- 8260130
TI  - Temperature correction factors derived from normal subjects may be invalid in
      demyelinating neuropathies.
AB  - This study investigates the temperature effect on motor nerve conduction velocity
      (MNCV) in patients with neuropathic processes. Fourteen subjects, ages 18-77 yr
      old, with a diagnosis of uremic polyneuropathies (UPN, n = 5), diabetic
      polyneuropathies (DPN, n = 6) or carpal tunnel syndrome (CTS, n = 3) and ten
      normal controls were studied. After limb cooling in a cold water bath for 30 min,
      skin temperatures were sequentially obtained from the volar midwrist. Motor
      conduction velocities were obtained at 2-3 degrees increments between 22 and 33
      degrees C. Results indicated a large individual variability; 0.1 to 1.8 in the
      median and 0.8 to 2.0 m/s/degrees C in the ulnar nerve when all three groups are
      considered together. There was a significant difference between the correction
      factors for control v DPN and control v CTS. A significant difference was also
      present for UPN v DPN and UPN v CTS (p < 0.05). There was a positive correlation
      (r = 0.746, p = 0.0001) between the baseline conduction velocities and the size
      of the correction factors in all the subjects. The effect of temperature on MNCV
      appears to be inversely correlated with the severity of conduction slowing or
      demyelination. These findings suggest that the use of a correction factor may be
      invalid when studying a demyelinated nerve, and that the extremity should be
      warmed to a specific temperature before an electrodiagnostic study.

PMID- 8260131
TI  - Sexual activities, concerns and interests of women with spinal cord injury living
      in the community.
AB  - A representative sample of 40 women selected from a community-based sampling
      frame of 661 men and women with spinal cord injury was studied for sexual
      activities, concerns and interests. Participants responded to a questionnaire and
      rating scales and were physically examined to establish their neurologic status.
      With respect to 11 other areas of life, sex life ranked tenth in importance and
      tenth in satisfaction. In the sample, 65% reported having had a physical
      relationship (not necessarily including intercourse) in the past 12 months. Areas
      of greatest concern were problems associated with urinary and bowel accidents and
      not satisfying a partner. Regarding topics of interest related to sexual
      activity, highest priorities were assigned to coping emotionally with changes in
      sexual functioning and helping a partner cope emotionally with limitations on
      sexual activity. Compared with a previously studied group of men with spinal cord
      injury, the women in the sample exhibited distinctive needs that were not being
      addressed sufficiently by rehabilitation professionals.

PMID- 8260132
TI  - Isokinetic dynamometric technique for spasticity assessment.
AB  - This study was conducted to determine the feasibility of quantifying spasticity
      by measuring the resistance to passive movement using an isokinetic dynamometer.
      A quantifiable method was developed by determining the summation of the four
      consecutive resisting torque amplitudes during flexion and extension of the knee
      at specified speeds and range of motion. A more rigorous assessment was made by
      finding the slope of the linear regression curve of torque-velocity data.
      Although the values of maximum torque were higher in the spastic group than in
      the normal group, the difference was statistically significant only when the sum
      of the torque amplitudes was considered (P < 0.0028). Values of the maximum
      torque as well as the sum of the torque amplitudes increased in a linear fashion
      (r > 0.75) with increasing velocity. The slopes of the torque-velocity curves
      were greater in spastic subjects than in normal subjects. The sensitivity to the
      rate of stretch was statistically greater (P < 0.0004) for the spastic group than
      normals only when the sum of torque amplitudes was considered. The corresponding
      data obtained during the flexion and extension of the knee were not statistically
      different (P > 0.05). Serial summation of torque amplitudes and measurement of
      slope in the torque-velocity curve are sensitive and repeatable methodologies for
      the measurement of spasticity assessment.

PMID- 8260133
TI  - Histologically proven pressure sore-related osteomyelitis in the setting of
      negative technetium bone scans. Case report.
AB  - Pressure sores are common in patients with spinal cord injury, stroke or
      debilitating medical illness. Contiguous osteomyelitis is a well recognized
      complication of pressure ulcers, but remains a challenging diagnostic and
      management problem. Technetium bone scan is purported to be an extremely
      sensitive, although nonspecific diagnostic test for osteomyelitis. Indeed, a
      negative bone scan is thought to virtually exclude bone infection. We report
      three cases of pressure sore-related polymicrobial osteomyelitis where technetium
      bone scan was normal, yet bone biopsy demonstrated characteristic histopathologic
      changes of osteomyelitis. These cases raise questions regarding the sensitivity
      of bone scanning in the setting of pressure sores, and they demonstrate the need
      for further investigation into the correlation between nuclear medicine scan
      results and bone biopsy histopathology. Bone biopsy remains the gold standard for
      diagnosis of osteomyelitis, which can be present in bone underlying a pressure
      ulcer, even in the setting of a normal bone scan.

PMID- 8260134
TI  - Spinal stenosis presenting as "the postpolio syndrome". Review of four cases.
AB  - The diagnosis of postpolio syndrome is based primarily on a thorough history
      supported by both clinical and laboratory examination. Similarly, the presence of
      an occult spinal stenosis may be suspected initially by a history of progressive
      lumbar or cervical radicular pain, as well as concomitant extremity weakness
      and/or myelopathic signs. Appropriate electrodiagnostic examinations, including
      somatosensory spinal-evoked potentials and electroneuromyography, as well as
      imaging studies, computer-assisted tomography scan, magnetic resonance imaging
      and/or myelography are all useful in confirming the clinical diagnosis of either
      cervical spinal stenosis or lumbar spinal stenosis in patients who also may have
      had a history of poliomyelitis. Four patients (three men and one woman)
      previously diagnosed as having postpolio syndrome were referred with predominate
      complaints of spinal and extremity pain as well as associated motor weakness. It
      was subsequently recognized that these patients, ranging in age from 45-65 yr,
      were actually presenting with symptomatic spinal stenosis. It was discovered that
      two patients had cervical spinal stenosis; the other two had lumbar spinal
      stenosis.

PMID- 8260135
TI  - Autonomic dysreflexia after brainstem tumor resection. A case report.
AB  - Autonomic dysreflexia is a poorly understood entity, typically occurring in the
      spinal cord-injured patient, with paroxysmal hypertension, bradycardia, severe
      throbbing headache, anxiety and sweating above the level of the lesion. An 18
      year-old man underwent removal of a hemangioblastoma from the inferior portion of
      the fourth ventricle, a region known as the area postrema. Postoperatively he
      exhibited signs of autonomic failure. He later developed recurrent paroxysmal
      episodes of abdominal pain, hypertension, skin flushing and headaches. He
      subsequently was found to have a gastric ulcer. Symptoms and signs significantly
      improved with its treatment. We postulate that diminished sympathetic outflow
      occurred as a result of the surgery, creating a situation similar to the spinal
      cord-injured patient. Autonomic dysreflexia was elicited as a consequence of the
      noxious input of the gastric ulcer. In other cases of brainstem tumor resection,
      unrecognized episodes of autonomic dysreflexia may occur. This case also
      indicates that sympathetic supraspinal control is located at the level of the
      medulla or higher.

PMID- 8260136
TI  - Practice parameters for physical medicine and rehabilitation. A commentary.

PMID- 8260137
TI  - Healing the self. The moral meaning of relationships in rehabilitation.
AB  - Ethical issues in rehabilitation include both clinical dilemmas and broader
      philosophic issues about the goals of rehabilitation and the nature of the
      provider-patient relationship. Two philosophic issues are explored in this paper.
      One involves the social conceptions of the human good that necessarily underlie
      rehabilitative care and provide its ethical context. The second is the way in
      which the clinical reality of rehabilitation challenges the ideals of autonomy
      and individualism central to mainstream bioethics. This paper argues that only
      with a moral vocabulary of relationships and transformative healing, rather than
      with a vocabulary of individualistic autonomy, can rehabilitation convincingly
      express its social goals and professional mission in an era of scarce resources.

PMID- 8260138
TI  - Rehabilitation at the crossroads. Financial and other considerations.

PMID- 8260139
TI  - Physical medicine and rehabilitation: trends in academic productivity.

PMID- 8260140
TI  - Changes in diurnal patterns related to changes in ozone levels.
AB  - Ozone is an ubiquitous air pollutant that affects both human health and
      vegetation. There is concern about the number of hours human populations in
      nonattainment areas in the United States are exposed to levels of O3 at which
      effects have been observed. As improvement in air quality is achieved, it is
      possible that O3 control strategies may produce distributions of 1-h O3
      concentrations that result in different diurnal profiles that produce greater
      potential exposures to O3 at known effects levels for multiple hours of the day.
      These concerns have prompted new analysis of aerometric data. In this analysis,
      the change in the seasonally averaged diurnal pattern was investigated as changes
      in O3 levels occurred. For the data used in this analysis, 25 of the 36 sites
      that changed compliance status across years showed no statistically significant
      change in the shape of the average diurnal profile (averaged by O3 season). For
      71 percent (10 out of 14) of the sites in southern California and Dallas-Fort
      Worth, Texas, that showed improvement in O3 levels (i.e., reductions in the
      number of exceedances over the years), but still remained in nonattainment, a
      statistically significant change in the shape of the seasonally averaged diurnal
      profile occurred. Based on the results obtained in this study, the evaluation of
      diurnal patterns may be useful for identifying the influence of changes in
      emission levels versus meteorological variation on attainment status. Using data
      from the southern California and Dallas-Fort Worth sites, which showed
      improvements in O3 levels, changes were observed in the seasonally averaged
      diurnal profiles.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260141
TI  - Transformations, lifetimes, and sources of NO2, HONO, and HNO3 in indoor
      environments.
AB  - Recent research has demonstrated that nitrogen oxides are transformed to nitrogen
      acids in indoor environments, and that significant concentrations of nitrous acid
      are present in indoor air. The purpose of the study reported in this paper has
      been to investigate the sources, chemical transformations and lifetimes of
      nitrogen oxides and nitrogen acids under the conditions existing in buildings. An
      unoccupied single family residence was instrumented for monitoring of NO, NO2,
      NOy, HONO, HNO3, CO, temperature, relative humidity, and air exchange rate. For
      some experiments, NO2 and HONO were injected into the house to determine their
      removal rates and lifetimes. Other experiments investigated the emissions and
      transformations of nitrogen species from unvented natural gas appliances. We
      determined that HONO is formed by both direct emissions from combustion processes
      and reaction of NO2 with surfaces present indoors. Equilibrium considerations
      influence the relative contributions of these two sources to the indoor burden of
      HONO. We determined that the lifetimes of trace nitrogen species varied in the
      order NO approximately HONO > NO2 > HNO3. The lifetimes with respect to reactive
      processes are on the order of hours for NO and HONO, about an hour for NO2, and
      30 minutes or less for HNO3. The rapid removal of NO2 and long lifetime of HONO
      suggest that HONO may represent a significant fraction of the oxidized nitrogen
      burden in indoor air.

PMID- 8260142
TI  - New trends in head and neck imaging.
AB  - The development of novel imaging techniques has exerted a larger influence on
      medical science than have any other advances in the last decade. The following
      occurrence are now evident in imaging for all medical disciplines: reduced use of
      ionizing radiation, abandonment of invasive methods, real-time properties,
      visualization of functional parameters, digitalization and pooling of
      information, as well as interaction of user with image information. A wide
      variety of imaging methods is now available clinically for the study of head and
      neck diseases. However, only picture archiving and communication systems (PACS)
      can efficiently handle and integrate information coming from multiple imaging
      modalities, such as computed tomography, magnetic resonance imaging, positron
      emission tomography, digital subtraction angiography and digital radiography.
      Such systems also incorporate image workstations that the surgeon can use for
      preoperative planning and even perioperative assistance. Current PACS are
      reviewed, since their future use may change the operating theater and also change
      surgical strategies.

PMID- 8260143
TI  - Surgery for congenital anomalies of the middle ear with mobile stapes.
AB  - In a series of 104 patients with congenital middle ear anomalies operated on from
      1964 to 1986, 27 cases were found in which the stapes footplate was mobile and
      the conductive deafness was due to an anomaly in the remaining part of the
      ossicular chain. In 8 cases the middle ear anomaly was caused by discontinuity of
      the ossicular chain owing to congenital malformation. In the other 19 ears,
      epitympanic fixation of the ossicular chain was observed, whether or not in
      combination with malformation of the stapes, incus or malleus. Ossicular chain
      reconstruction produced an improvement of at least 15 dB in 6 of the first 8
      cases with discontinuity of the ossicular chain. The mean gain was 31 dB.
      Epitympanotomy with exposure of the fixed ossicle and if necessary ossicular
      chain reconstruction led to an improvement of at least 15 dB in 12 of the 19
      ears, with a mean gain of 28 dB.

PMID- 8260144
TI  - Effects of increased cerebrospinal fluid pressure on cochlear and cerebral blood
      flow.
AB  - We investigated the effects of increased cerebrospinal fluid (CSF) pressure on
      cochlear blood flow (CoBF) and cerebral blood flow (CBF) in guinea pigs. CoBF and
      CBF were recorded simultaneously using two laser-Doppler flowmeters, and blood
      flow volume in each part of the cochlea and the brain was measured by the non
      radioactive microsphere method. CoBF was reduced by increased CSF pressure but
      the reduction was not persistent. Although inner ear pressure was elevated to the
      same level as CSF pressure, CoBF was not decreased by the pressure elevation as
      much as was CBF. Our results suggest that CoBF is relatively resistant to
      increases in CSF pressure.

PMID- 8260145
TI  - Role of thromboxane A2 in a microcirculation disorder of the rat inner ear.
AB  - Since thromboxane (TX) A2 causes vasoconstriction and platelet aggregation, we
      evaluation the effect of a TXA2 receptor antagonist (vapiprost) and a TXA2
      synthetase inhibitor (Y-20811) on a microcirculation disorder in the rat inner
      ear that was induced by a photochemical reaction between an intravenous injection
      of rose bengal (RB) and green light. A gradual decrease of the cochlear action
      potential (CAP) to an 8 kHz sound stimulus was measured with an
      electrocochleogram and occurred after the RB injection. The CAP then disappeared
      5 min after the injection of RB. Both vapiprost and Y-20811 significantly
      prolonged the time required to complete suppression of the CAP as compared with
      saline as control. These findings indicate that TXA2 may play an important role
      in microcirculation disorders in the rat inner ear.

PMID- 8260146
TI  - Structure, pharmacology and function of GABA-A receptors in cochlear outer hair
      cells.
AB  - There is evidence that the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABA) is released from some efferent olivocochlear nerve endings terminating at
      outer hair cells (OHCs). Using monoclonal antibodies against postsynaptic GABAA
      receptor from bovine cerebral cortex we confirm the presence of GABA and
      benzodiazepine bindings sites of alpha- and beta-subunits of GABAA receptors at
      the basal pole of isolated OHCs. Whole-cell recording with viable OHCs revealed
      that the application of 10(-3)-10(-8) M GABA to the cell surface was followed by
      a concentration-dependent hyperpolarization of the outer cell membrane.
      Hyperpolarization was increased in the presence of 2.5 x 10(-5) M chlorazepate, a
      benzodiazepine derivative. Electrophysiological effects caused by GABA alone or
      in combination with chlorazepate were specifically inhibited by 10(-6) M of the
      GABA-receptor antagonist picrotoxin. Moreover, 10(-5)-10(-7) M GABA caused
      reversible slow elongation of the cylindrical hair cell body in OHCs examined.
      These neurotransmitter-induced motile responses were specifically blocked by 10(
      4) M picrotoxin. The results suggest that a subpopulation of OHCs express alpha-
      and beta-subunits of GABAA receptors which both form a GABA/benzodiazepine
      receptor complex at the basal pole of isolated OHCs. These receptors are thought
      to allow GABA which is released from efferent auditory nerve terminals to bind to
      the cell surface of OHCs, resulting in GABAA-receptor activation. This probably
      gates a GABAA-receptor-associated chloride channel in the postsynaptic OHC
      membrane, allowing hyperpolarization and elongation of the cell.

PMID- 8260147
TI  - Growth and spread of squamous cell carcinoma of the floor of the mouth.
AB  - Forty-eight specimens of carcinoma of the floor of the mouth were analyzed
      histologically by step serial sections. Five tumors were so-called superficial
      spreading carcinomas with large fields of cancerous mucosa, while 43 specimens
      showed advanced vertical growth into adjacent structures. Three different routes
      of invasion could be defined. The region of the sublingual gland was the main
      pathway in 23 cases. The space between the intrinsic muscles of the tongue and
      the genioglossus muscle was the main direction of infiltration for 14 tumors.
      Only 6 specimens showed direct invasion into the intrinsic tongue muscles. There
      was a good correlation between tumor thickness and the occurrence of metastases.
      Twenty-six patients (54%) showed metastases in regional lymph nodes and 13
      patients with submandibular metastases already had developed metastases along the
      jugular vein. Unilateral or bilateral functional neck dissections remained the
      standard treatment procedure for all cases with depths of invasion over 5 mm. To
      avoid local tumor recurrences, patterns of invasion have to be considered. Soft
      tissue structures like the sublingual gland, intrinsic tongue muscles,
      genioglossus muscle and geniohyoid muscle have to be resected routinely.
      Management of the mandible should be conservative if radiological and clinical
      investigations are negative.

PMID- 8260148
TI  - Maturation of auditory evoked potentials in young guinea pigs with binaural
      conductive hearing loss.
AB  - A reversible conductive hearing loss produced during the first 4 weeks post
      partum caused marked alterations in the development of click-evoked auditory
      brainstem (ABR) and middle latency (MLR) responses in guinea pigs. The early
      component PI in the ABR in controls showed adult-like latencies at the time of
      birth, while the later ABR components PIII and PV and all components investigated
      in the MLR showed postnatal development characterized by a shortened latency that
      persisted for the whole period of investigation. The course of the ABR latencies
      showed the sharpest decrease during the first 2-3 weeks of life, while that for
      the MLR took place during the first 5 weeks. In addition to the increased ABR
      thresholds and lengthened ABR latencies due to the conductive hearing loss,
      development of the ABR inter-peak latencies (IPL) and MLR latencies was retarded.
      The IPL reached control values 1 week after the end of the deprivation phase,
      while the delay in MLR started later (4th week) and lasted longer than did that
      in the ABR. These findings showed that a long-lasting postnatal conductive
      hearing loss does not generate sustained impairment at the level of the brainstem
      but can evoke longer-lasting deficiencies at higher stations of the auditory
      pathway.

PMID- 8260149
TI  - Click-evoked otoacoustic emissions in a child with unilateral deafness.
AB  - In a 6-year-old boy with idiopathic unilateral deafness, click-evoked otoacoustic
      emissions were recorded in both ears with similar amplitudes and time courses.
      Following stimulation of the deaf ear, no component of auditory-evoked brainstem
      potentials was recorded. No space-occupying lesion was observed with high
      resolution CT. At retest 1 year later these results were unchanged. In the deaf
      ear electrostimulation of the cochlear nerve was performed using an ear canal
      electrode. At a stimulus current of 20 microA the body consistently reported
      hearing sensation. Click-evoked otoacoustic emission indicated good outer hair
      cell function. Hearing sensation at low stimulus intensities with
      electrostimulation indicated fairly good functions of the cochlear nerve.
      Considering also the results of imaging and auditory-evoked potentials, findings
      suggested that the deafness was due to an inner hair cell disorder.

PMID- 8260150
TI  - New ophthalmic lasers for the evaluation and treatment of retinal disease.
AB  - Ophthalmic lasers are used as diagnostic as well as therapeutic modalities in
      patients with retinal diseases. Recent advances in laser technology have allowed
      more convenient selection of wavelength and a wide variety of delivery systems is
      available to deliver the laser energy to the retina. In addition, newer lasers
      that disrupt and cut tissue will become available for use in patients with
      retinal diseases. The use of imaging lasers and lasers in combination with dyes
      selectively to enhance their effects have become useful in diagnosis and
      understanding of pathophysiology of diseases. These lasers will also be
      therapeutically useful.  This manuscript delineates the new types of diagnostic
      and therapeutic lasers, new imaging dyes and techniques as they apply to retinal
      diseases as well as the principles of laser-tissue interaction as applied to the
      retina. This should allow the ophthalmologist who treats patients with retinal
      diseases to make more intelligent decisions regarding the use and acquisition of
      laser systems.

PMID- 8260151
TI  - Prospective evaluation of one surgeon's first 100 cases of endocapsular
      phacoemulsification cataract surgery.
AB  - In this series of one surgeon's first 100 cases of endocapsular
      phacoemulsification cataract surgery (EPECS), believed to be the first truly
      prospective study of its kind, 86% of patients achieved corrected vision of 6/6
      to 6/4; 96% achieved vision of 6/12 or better; and excluding those with pre
      existing pathology, 99% achieved 6/12. Posterior capsular rupture occurred in 11
      cases, with vitrectomy being required in eight cases. Detailed analysis of the
      100 cases is provided.

PMID- 8260152
TI  - The Koch endocapsular punch. A report on its use in 96 consecutive cases.
AB  - The technique of endocapsular cataract extraction and intraocular lens
      implantation surgery provides optimal surgical conditions and more reliable
      intraocular lens positioning in the capsular bag. Several capsulectomy techniques
      are in use to remove anterior capsule from the central zone. The Koch
      endocapsular punch provides a new technique for creating a continuous anterior
      capsulectomy. In this study the Koch punch was used in 96 eyes consecutively
      undergoing intended endocapsular cataract extraction and intraocular lens
      implantation. Ninety-five eyes had appropriate lens centration at six months.
      There were no cases of vitreous loss. Ninety-nine per cent of cases had visual
      acuity of 6/6 or better at six months. This data demonstrates the Koch
      endocapsular punch to be an effective and safe means for anterior capsulectomy.

PMID- 8260153
TI  - Endonasal dacryocystorhinostomy--primary and secondary.
AB  - An endonasal approach was used to restore lacrimal drainage in both primary and
      secondary obstructions. Patients in the primary group had a history of keloid
      scar formation, or wished to avoid a scar and declined to have surgery performed
      via an external approach. Patients in the secondary group had undergone one or
      more previous unsuccessful lacrimal drainage repairs. A fibreoptic endonasal
      telescope, linked to a video monitor, and appropriate nasal and lacrimal
      instruments, were used. The approach proved highly successful, in both anatomical
      and functional terms, in each group. In the secondary group, the endonasal
      approach allowed direct visualisation and repair of both nasal and lacrimal
      causes of failure; this approach is our preference in this group. In the primary
      group, endonasal instrumentation had no advantage over a conventional external
      operation, other than avoiding a scar. The application of laser technology may
      make the endonasal approach a realistic option in primary DCRs as well.

PMID- 8260154
TI  - Laser trabeculoplasty--argon or diode?
AB  - It is important to compare the pressure-lowering effect of the recently
      introduced diode laser with that of the argon laser currently used for
      trabeculoplasty, since there is a considerable difference in their wavelengths.
      In 50 consecutive eyes of 50 patients argon laser trabeculoplasty (ALT) produced
      a fall from 23 to 18 mmHg at three months compared with a fall from 23 to 19 mmHg
      at three months with diode laser trabeculoplasty (DLT). This difference was not
      statistically significant. Comparing the magnitude of the fall in intraocular
      pressure (IOP) in these two groups of 50 eyes, 28 patients achieved a fall of 5
      mmHg or more with ALT and 17 with DLT and this difference was significant (chi 2
      1df = 4.04, P < 0.05). Comparing 23 paired fellow eyes which both needed laser
      trabeculoplasty, those treated with ALT achieved a fall from 22 to 17 mmHg
      compared with a fall from 22 to 19 mmHg with DLT and this difference was
      statistically significant (T = 53.5, P < 0.02, Wilcoxon matched-pairs signed rank
      test). These results suggest that the pressure lowering effect of DLT is
      comparable to that of ALT, but ALT is somewhat more effective as shown by a
      greater fall in IOP after ALT than DLT in fellow eyes of the same patient. In the
      unpaired eyes the number of falls of 5 mmHg or more was significantly greater
      with ALT than DLT, although the mean fall was not statistically different between
      the two groups.

PMID- 8260155
TI  - Identification of cytomegalovirus in vitreous using the polymerase chain
      reaction.
AB  - A presumptive clinical diagnosis of cytomegalovirus (CMV) retinitis was made in
      two patients presenting with atypical ophthalmologic findings. The diagnosis was
      confirmed by finding specific CMV DNA sequences in sampled vitreous fluid using a
      polymerase chain reaction (PCR) based assay. Neither of these patients yielded
      CMV on culture or PCR of peripheral blood leucocytes, nor was CMV present in
      tears or urine of either patient. Serum antibody titres were stable and did not
      help in establishing the diagnosis. This report suggests that CMV retinitis can
      occur in the absence of disseminated CMV disease.

PMID- 8260156
TI  - NADPH-diaphorase histochemistry reveals cone distributions in adult human
      retinae.
AB  - NADPH-diaphorase histochemistry was used to identify and analyse the topography
      of cones in adult human retinae (in the age range 44 to 68 years). Retinae were
      treated for NADPH-diaphorase reactivity, present in vascular walls, amacrine
      cells and cone and rod outer segments; a subpopulation of less intensely reactive
      profiles, morphologically resembling cones, possibly represents the blue cone
      population. Regularly spaced pairs of cones (one intensely labelled and one
      weakly labelled cone) were also apparent throughout the retina, and were most
      common along the horizontal meridian, particularly towards the periphery. The
      diameters and distributions of labelled cone outer segments were assessed using
      image analysis. Cone density in the adult retina ranged from 2000 per mm2 in the
      temporal periphery, to 82,000 to 120,000 per mm2 at the fovea centralis.
      Distribution patterns confirmed the presence of a cone streak, extending from the
      foveal region into nasal retina, but no evidence of superior-inferior asymmetry
      was detected.

PMID- 8260157
TI  - Benign intracranial hypertension in chronic myeloid leukemia.
AB  - We present a patient with chronic myeloid leukemia (CML) who had marked bilateral
      disc swelling as part of his initial presentation. This occurred in the setting
      of raised intracranial pressure (ICP), with normal cerebrospinal fluid (CSF)
      composition and cell content, and normal neuroimaging. We discuss the possible
      mechanisms which could lead to disc swelling in CML and conclude that the raised
      ICP and subsequent papilloedema in our patient were the result of poor absorption
      of CSF into the dural venous sinuses. We propose that the very high white cell
      count (WCC) led to a hyperviscosity state which resulted in poor absorption of
      CSF and in so doing, created a clinical picture of benign intracranial
      hypertension (BIH).

PMID- 8260158
TI  - Paraquat causes chronic ocular surface toxicity.
AB  - We describe a case of topical exposure to a commercial solution of paraquat.
      Chronic, severe ocular surface destruction resulted, probably due to absorption
      of the herbicide into the surface tissues, facilitated by a surfactant present in
      the preparation, and to intracellular redox cycling of the paraquat cation.
      Ocular paraquat toxicity is described and explained in the context of the
      toxicity of systemic absorption.

PMID- 8260159
TI  - Chronic corneal ulceration. An unusual presentation of metastatic breast
      carcinoma.
AB  - A patient presented with a history of chronic corneal ulceration and corneal
      hypoaesthesia. This proved to be an unusual presentation of breast carcinoma
      metastatic to the sphenoidal wing. This was an unexpected diagnosis in view of
      the long duration of ocular signs without other evidence of metastatic disease.

PMID- 8260160
TI  - Retinopathy after low-dose retinal irradiation.
AB  - A 28-year-old man, after subtotal resection of a Grade I-II frontal lobe
      astrocytoma, received 5600 cGy of radiotherapy in 200 cGy fractions to residual
      intracranial tumour. One year later he presented with severe bilateral
      retinopathy which, in appearance was consistent with retinopathy from
      irradiation. Total irradiation received by the retina of each eye (< 50 to 1500
      cGy) was far less than the dose which commonly produces radiation retinopathy.
      Also, the pattern of retinopathy did not reflect the distribution of radiation
      received by the eye. Alternative causes for the retinopathy were sought but not
      found. Proliferative retinopathy occurred in each eye and one eye developed a
      dense vitreous haemorrhage. Argon laser pan-retinal photocoagulation controlled
      the neovascularisation in the other eye. This patient has developed severe
      retinal ischaemia after a low dose of retinal irradiation.

PMID- 8260161
TI  - Severe epistaxis--an unusual complication of lacrimal probing.
AB  - Severe epistaxis after combined nasolacrimal duct probing and cardiac
      catheterisation in a one-year-old child is reported. The epistaxis followed
      streptokinase infusion given as treatment for femoral artery thrombosis secondary
      to cardiac catheterisation and necessitated nasal packing and blood transfusion.
      The authors recommend that probing not be undertaken in conjunction with another
      procedure if anticoagulant and/or thrombolytic agents are likely to be required.

PMID- 8260162
TI  - Optic disc haemorrhages: comparison of accessory magnifying attachments for the
      Zeiss retinal camera.

PMID- 8260163
TI  - Iconoclastic observation on eyelash dandruff.

PMID- 8260164
TI  - Three-dimensional echocardiographic volume computation: in vitro comparison to
      standard two-dimensional echocardiography.
AB  - Two-dimensional (2D) echocardiographic methods for quantitative left ventricular
      volume computation have been shown to have a low predictive accuracy and
      reproducibility. To address the problem of geometric assumptions and image plane
      positioning errors inherent in 2D echocardiography, three-dimensional (3D)
      echocardiographic systems have been constructed that provide spatial registration
      and display of transducer-image position and orientation. Although 3D
      echocardiography has been shown to accurately measure volume in vitro and in
      vivo, only preliminary data exist demonstrating its superiority over standard 2D
      echocardiography. We calculated the volume of 30 water-filled latex balloon
      phantoms of varying size (40 to 200 ml) and shape using each method. Fifteen
      phantoms were nondistorted (ellipsoid or pear shaped); 15 were symmetrically
      distorted (dumbbell shaped). Although both 2D and 3D echocardiography showed an
      excellent correlation to the true volume (r = 0.97 and 0.99, respectively), the
      standard error of the estimate for 2D echocardiography was twofold larger than
      for 3D echocardiography (SEE = 6.7 ml and 3.52 ml, respectively). The true volume
      was slightly underestimated by 3D echocardiography (-2.83 ml), whereas 2D
      echocardiography overestimated a similar amount (+2.87 ml). The accuracy and
      variability for 2D echocardiography were significantly poorer (5.22% +/- 5.66%
      and 5.29% +/- 5.6%, p = 0.001 and 0.002, respectively) as compared with 3D
      echocardiography (3.7% +/- 2.65% and 2.65% +/- 1.9%, respectively). We conclude
      that 3D echocardiography with guided image plane positioning and a novel
      algorithm for volume computation (polyhedral surface reconstruction) achieves
      significantly more accurate and reproducible results than conventional 2D
      echocardiography with the modified Simpson's rule.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8260165
TI  - Accurate determination of left ventricular ejection fraction by transesophageal
      echocardiography with a nonvolumetric method.
AB  - The multiple diameter method previously described and validated for transthoracic
      echocardiography (TTE) determines ejection fraction (EF) by use of the average of
      several left ventricular (LV) diameters from multiple views measured at the base,
      midthird, and distal third of the LV combined with an estimate of the shortening
      fraction of the long axis (delta L). This method may be ideal for transesophageal
      echocardiography (TEE) because it does not require tracing of the endocardial
      contour or volume determinations. Accordingly, EF was calculated with the
      multiple diameter method in 20 patients in whom TTE and TEE were performed within
      1 hour of each other. EF by TTE averaged 49% +/- 20% and ranged from 14% to 80%.
      The multiple diameter method was modified for TEE as follows: (1) three diameters
      were taken from the four-chamber view (base, mid-LV, and distal LV) and four from
      the transgastric view (approximately at 45 degrees from each other), (2) because
      the LV apex is not well seen by TEE, delta L was estimated from the descent of
      the mitral anulus towards the apex as 0.15, 0.10, 0.05, or 0 for a descent of >
      or = 10, 6 to 9, 3 to 5 or < or = 2 mm, respectively. EF by TEE averaged 48% +/-
      21% and correlated very well with EF by TTE (r = 0.98; y = 1.03x-2.7). The
      diameter method was tested prospectively in 30 patients undergoing coronary
      artery bypass surgery. TEE and TTE were performed within 5 minutes of each other
      with the patients asleep before initiation of surgery.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8260166
TI  - Two-dimensional echocardiographic automated border detection accurately reflects
      changes in left ventricular volume.
AB  - The objective of this study was to determine the relationship of on-line
      measurements of left ventricular cavity area generated by echocardiographic
      automated border detection to true volume measured by an intraventricular balloon
      in an isovolumically contracting isolated canine heart preparation. Seven excised
      dog hearts had placement of an intraventricular balloon and were perfused in an
      ex vivo apparatus. Left ventricular area data from the midventricular short-axis
      plane and pressure data were recorded on a computer through a customized hardware
      and software interface with the ultrasound system. Left ventricular volumes were
      varied from 5 ml to maximal values (30 to 40 ml) at 1-milliliter increments.
      Three increasing and decreasing volume ramps were analyzed on each of seven
      hearts for a total of 1260 simultaneous measurements. Linear regression analysis
      correlated mean automated border detection area with absolute volume from each
      preparation. A predominantly linear relationship was observed with an average
      correlation of r = 0.97 (y = 0.16x-0.69, SEE = 0.31 cm2, p < 0.01). Left
      ventricular area measures for six of seven dogs varied little during isovolumic
      contraction (< 0.4 cm2) but did show a systematic cardiac cycle-related
      variability in one dog (28% change in area, maximum to minimum, over all
      volumes). In conclusion, the relationship between cross-sectional area and left
      ventricular volume was predominantly linear and varied little during isovolumic
      contractions in the normal canine left ventricle. Echocardiographic automated
      border detection appears to be a promising method to reflect changes in left
      ventricular volume.

PMID- 8260167
TI  - Transesophageal echocardiographic evaluation of left ventricular function during
      intraaortic balloon pump counterpulsation.
AB  - Transesophageal echocardiography was used to study the effects of intraaortic
      balloon pump counter pulsation (IABP) on left ventricular dimensions and function
      in 16 hypotensive patients after cardiac surgery. The short-axis cross section at
      midpapillary muscle level was used to determine systolic and diastolic
      dimensions. We found a significant decrease in end-systolic and end-diastolic
      area and increase in fractional area change during IABP-supported circulation.
      Regional area ejection fraction analysis demonstrated an improvement during IABP
      of impaired (particularly severely impaired) function at baseline. We conclude
      that both regional and global left ventricular function improve by the use of
      IABP in conjunction with a decrease of left ventricular size.

PMID- 8260168
TI  - The role of echocardiography in heart transplantation.
AB  - Echocardiography has gained increasing importance as an imaging modality in the
      care of the cardiac transplant recipient. Its utility in detecting the
      complications of transplantation, with special reference to the diagnosis of
      rejection and graft arteriosclerosis, is discussed. On the basis of a review of
      the current literature, an outline for serial echocardiographic studies is
      proposed.

PMID- 8260169
TI  - Pediatric endomyocardial biopsy performed solely with echocardiographic guidance.
AB  - Endomyocardial biopsy has had limited utilization for the diagnosis of myocardial
      disease in the pediatric population. Through the use of echocardiography for
      guidance, we attempted 155 consecutive biopsies in 33 patients. A successful
      biopsy was performed 151 times, including 48 (31%) in infants less than 6 months
      of age. Biopsies were performed with a right internal jugular approach using 3F,
      5F, and 7F bioptomes. A combination of apical four-chamber and parasternal short
      axis views could visualize the passage of the bioptome into the ventricle and the
      action of the jaws. There was no case of ventricular perforation. After biopsy
      one transplant recipient was left with an increase in the amount of preexisting
      tricuspid regurgitation by color flow mapping echocardiography. These results
      demonstrate that echocardiographically guided endomyocardial biopsies may be
      safely performed over a wide range of patient sizes. The increased portability,
      lack of radiation exposure, and the simultaneous visualization of the bioptome
      and chamber wall combined with these results indicate that echocardiographically
      guided endomyocardial biopsies should be considered the technique of choice for
      the pediatric population.

PMID- 8260170
TI  - Systolic coronary flow reversal and abnormal diastolic flow patterns in patients
      with aortic stenosis: assessment with an intracoronary Doppler catheter.
AB  - Decreased left ventricular coronary flow reserve has been reported in patients
      with normal coronary arteries and left ventricular hypertrophy in association
      with aortic stenosis. However, phasic coronary flow characteristics have not been
      analyzed in detail in similar patients. The purpose of this study is to assess
      phasic coronary flow characteristics and their relation to hemodynamic parameters
      in patients with aortic stenosis. Coronary flow velocities were recorded in the
      left anterior descending artery with a 20 MHz Doppler catheter in nine patients
      with aortic stenosis and nine control subjects with normal coronary arteries.
      Patient aortic valve area ranged from 0.34 to 0.51 cm2. Flow reversal was
      observed in systole in all patients with aortic stenosis, and time velocity
      integrals of systolic flow were significantly smaller in patients with aortic
      stenosis than in controls (-0.3 +/- 2.3 vs 4.0 +/- 1.1 cm, p < 0.01). The time to
      peak diastolic velocity corrected by square root R-R interval was prolonged and
      the velocity half-time from peak diastolic velocity corrected by square root R-R
      interval was shorter in patients with aortic stenosis than in controls (5.3 +/-
      1.1 vs 4.0 +/- 0.5, p < 0.01, 8.0 +/- 2.6 vs 13.0 +/- 3.3, p < 0.01,
      respectively). Peak velocity and time velocity integral of flow reversal showed
      significant correlations with mean pressure gradient across the aortic valve (y =
      1.3x + 37.3, r = 0.72, p = 0.03, y = 11.3x + 41.2, r = 0.81, p < 0.01,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260171
TI  - Left ventricular outflow tract obstruction: an indication for intraoperative
      transesophageal echocardiography.
AB  - Transesophageal echocardiography (TEE) provides detailed anatomic imaging of both
      discrete and complex forms of left ventricular outflow tract (LVOT) obstruction,
      and Doppler techniques provide additional information regarding the site,
      mechanism, and severity of the obstruction. Because the transaortic surgical
      approach to LVOT obstruction often provides limited direct visualization during
      surgery, we sought to evaluate the utility of intraoperative TEE during surgery
      for LVOT obstruction. We tested the hypotheses that intraoperative TEE would (1)
      be useful in defining the level and nature of LVOT obstruction, (2) serve to
      direct the surgical approach, (3) define the adequacy of relief of LVOT
      obstruction, and (4) detect surgical complications. Study population consisted of
      a consecutive series of 27 infants and children undergoing surgery for LVOT
      obstruction. Patient age ranged from 0.5 to 17.9 years, and weight from 5.4 to
      71.2 kg. In 14 patients LVOT obstruction resulted from a discrete membrane,
      whereas 13 had complex forms of LVOT obstruction. Fully anesthetized and
      monitored patients were examined with 5 MHz TEE probes appropriate to the size of
      the patient. In the 14 patients with discrete LVOT obstruction, discrete
      membranes were identified by TEE in all; gradients ranged from 36 to 75 mm Hg. In
      13 of 14 patients, postbypass TEE demonstrated removal of the membrane and
      excellent relief of gradients. In one of these patients, TEE demonstrated a small
      ventricular septal defect acquired during resection; the patient was returned to
      bypass for closure. In one patient, return to bypass for further resection of
      LVOT obstruction was prompted by TEE demonstration of a high residual gradient.
      In the 13 patients with complex LVOT obstruction, TEE demonstrated the complexity
      of LVOT obstruction in all. Gradients ranged from 4 to 95 mm Hg. Although this
      information was used in surgical planning, five patients had high residual
      gradients after bypass and underwent further resection. An additional two were
      returned to bypass for mitral valve replacement. Overall, 8 of 27 patients
      (29.6%) were returned to bypass based on TEE demonstration of residual anatomic
      or hemodynamic abnormalities. This occurred significantly more frequently in
      complex LVOT obstruction than in discrete LVOT obstruction (p = 0.045). We
      conclude that intraoperative TEE has substantial utility in the demonstration of
      site, mechanism, and severity of LVOT obstruction and for surgery designed to
      relieve LVOT obstruction. We believe that TEE should be an integral part of
      surgical management of LVOT obstruction.

PMID- 8260172
TI  - Traumatic left ventricular papillary muscle rupture: the role of transesophageal
      echocardiography in diagnosis and surgical management.
AB  - We report a case of left ventricular posteromedial papillary muscle rupture
      caused by blunt chest trauma. Transesophageal echocardiography was used to
      establish the diagnosis and to assist with surgical repair of the mitral valve
      apparatus. Echocardiographic findings of the acutely ruptured papillary muscle
      are reviewed.

PMID- 8260173
TI  - Invasive intracardiac aspergillosis with widespread embolization.
AB  - Intracardiac extension of pulmonary aspergillosis is uncommon. We report a case
      of a patient with chronic necrotizing pulmonary aspergillosis without clinical
      evidence of cardiac disease in whom transthoracic echocardiography revealed an
      intracardiac mass. A subsequent transesophageal examination clearly defined a
      large and complex mass in the left atrium and pulmonary artery. Autopsy performed
      after cardiopulmonary arrest confirmed the presence of direct cardiac invasion of
      pulmonary aspergillosis with widespread embolization. This case illustrates the
      possibility of direct intracardiac extension of pulmonary aspergillosis and the
      value of transesophageal echocardiography in establishing the diagnosis.

PMID- 8260174
TI  - Transesophageal echocardiography and right atrial infarction.
AB  - Transesophageal echocardiographic findings in right atrial infarction are
      described. In three patients with myocardial infarction of one or both
      ventricles, the association of right atrial myocardial infarction was suspected
      because of anatomic (two-dimensional) and hemodynamic (Doppler) alterations
      obtained from transesophageal images. Transesophageal interrogation may prove
      widely applicable in the evaluation of patients with suspected right atrial
      infarction.

PMID- 8260175
TI  - Left ventricular pseudoaneurysm complicating mitral valve replacement:
      transesophageal echocardiographic diagnosis and impact on management.
AB  - Left ventricular pseudoaneurysm formation after mitral valve replacement,
      although infrequent, is a serious complication with potential catastrophic
      results. We describe a case of an anterobasal pseudoaneurysm compressing all
      branches of the left coronary artery, which was missed by initial transthoracic
      echocardiography and was well characterized with the transesophageal approach.
      Although the pseudoaneurysm was detected at contrast ventriculography, the
      transesophageal study provided new specific details regarding the exact site of
      origin of the pseudoaneurysm and its relationship to the coronary arteries that
      significantly influenced planning the surgical procedure and patient management.

PMID- 8260176
TI  - Breast cancer in Denmark. Incidence, risk factors, and characteristics of
      survival.
AB  - In Denmark, incidence of female breast cancer remained constant from 1943 to
      around 1960, whereafter a steady increase has occurred, the level today being
      about 50% higher than in 1960. No equivalent rise has been observed for breast
      cancer mortality. Influence of hormonal and dietary factors on breast cancer risk
      and survival was evaluated in a combined population-based case-control and follow
      up study, including 2,445 women, aged less than 70 years, diagnosed with breast
      cancer in Denmark between 1 March 1983 and 31 August 1984, identified from the
      files of the nation-wide clinical trial of the Danish Breast Cancer Co-operative
      Group (DBCG) and the Danish Cancer Registry. The control group was an age
      stratified random sample of the general female population, selected from the
      Central Population Register. Data on risk factors were collected by self
      administered questionnaires. Clinical and pathological tumour characteristics
      derived from DBCG. The case-control analysis confirmed an overall increased risk
      of breast cancer associated with urban residence, high social status,
      nulliparity, early age at menarche, late age at natural menopause, hormonal
      replacement therapy, high dietary fat intake, and high alcohol consumption in a
      subgroup. It failed to detect an association with age at first childbirth, oral
      contraceptives, smoking, intake of vegetables, tea, coffee, and sweeteners.
      Survival was determined by tumour size, skin invasion, number of positive lymph
      nodes, and grade. There was no relation between survival and reproductive or
      hormonal factors, dietary variables, alcohol consumption, or smoking. However, a
      complex relationship may exist between survival and body mass index.

PMID- 8260177
TI  - Association between cervical and penile cancers in Madras, India.
AB  - A total of 4,995 cervical and 311 penile cancer cases were registered in the
      Madras Population-Based Cancer Registry at the Cancer Institute (WIA), Madras,
      India, in 1982-1990. The parameters analyzed were age at the time of diagnosis,
      educational level, marital status, and religion. Peak incidence of carcinoma of
      the cervix was seen in the age group 55-59 years. The incidence of penile cancer
      increased consistently with age. Among cervical cancer patients, the incidence
      was significantly higher among illiterates and among those who had an education
      for 12 years or less than among those with over 12 years of education. The
      incidence of cervical cancer was low among Muslim women compared to Hindu and
      Christian women, and penile cancer was not seen at all among Muslim men. Our
      results re-emphasize the importance of circumcision in the reduction of the risk
      of both cervical and penile cancers.

PMID- 8260178
TI  - Skin cancer in African albinos.
AB  - A review of 775 normally pigmented Africans and 18 African albinos with malignant
      skin tumours showed that squamous cell carcinoma was the most common tumour type,
      in contrast to Caucasians, in whom basal cell carcinoma is most frequent. In
      African albinos squamous cell carcinoma of the head and neck region was most
      frequent. However, the proportion of basal cell carcinomas was low also among
      albinos but higher than among normally pigmented patients. In contrast to the
      normally pigmented patients, there were no squamous cell carcinomas on the limbs
      in albino patients. We suggest that this difference was due to environmental
      factors, such as chronic leg ulcers, which might have been less influential in
      the albinos, who seldom lived more than 30 years. No cases of cutaneous melanoma
      or Kaposi sarcoma were found in the albino group.

PMID- 8260179
TI  - Psychiatric morbidity among cancer patients and its relationship with awareness
      of illness and expectations about treatment outcome.
AB  - Sixty consecutive patients admitted to an oncology unit in a general hospital
      were systematically assessed to determine the prevalence of psychiatric
      disorders. Patients' awareness of the diagnosis of cancer and their perception of
      treatment intention and outcome were assessed independently by another
      investigator who was blind to the psychiatric diagnosis. Forty percent of the
      sample had a diagnosis of psychiatric disorder, based on the Diagnostic and
      Statistical Manual for Mental Disorders (3rd edition, revised). Adjustment
      disorders comprised most of the psychiatric diagnoses. Major depression was seen
      in 8 (13%) patients. One third of the patients were estimated to be unaware of
      the diagnosis of cancer, and 82% of patients perceived the treatment given as
      curative. Psychiatric morbidity was significantly less common in patients who did
      not know they had cancer, and in those who considered treatment as curative. The
      prevalence of depressive disorders in our sample was higher than in medical
      inpatients. It is concluded that psychiatric disorders, especially affective
      disorders, are common among cancer patients. Awareness of nature of the illness
      and expected outcome can affect the prevalence of psychiatric morbidity. Further
      studies investigating the relationship between psychiatric morbidity and duration
      of illness, type and stage of cancer, disabilities and coping strategies are
      warranted.

PMID- 8260180
TI  - Circulating pancreatic polypeptide in patients with adenocarcinoma of the bile
      duct.
AB  - Using radioimmunoassay methods, the blood of patients with pancreatic tumors was
      screened for circulating polypeptide hormones. This screening discovered
      pancreatic polypeptide in abnormally high concentration in the serum of six of
      seven patients with adenocarcinomas of the bile duct. The assay appears to be
      very sensitive finding excessive residual pancreatic polypeptide production after
      palliative resections. Serum pancreatic polypeptide assays warrant evaluation as
      an aid in the diagnosis and management of patients with bile duct tumors.

PMID- 8260181
TI  - Prognostic value of serum tetranectin in patients with metastatic breast cancer.
AB  - To evaluate serum tetranectin as a prognostic marker before first-line
      chemotherapy, serum levels were studied in 67 patients with metastatic breast
      cancer. In the Cox analyses, the relative risk (RR) for death of cancer varied
      with the cut-off level of serum tetranectin. A maximal RR of 5.0 was found for
      patients with serum tetranectin < or = 5.4 mg/l. The maximal RR of death for the
      other prognostic variables were multiple metastases 2.8, and for a poor
      performance status 2.0. Testing for the outcome, progressive disease, a maximal
      RR of 3.8 was found for patients with serum tetranectin < or = 5.3 mg/l, a
      maximal RR of 3.7 for multiple metastases and a maximal RR of 1.8 for a poor
      performance status. Significantly lower serum tetranectin values were found in
      patients with a poor treatment response compared to well responding patients.
      Serum tetranectrin seems to be useful as an additional prognostic factor in
      metastatic breast cancer.

PMID- 8260182
TI  - A feasibility study of concomitant boost radiotherapy for patients with cancer of
      the supraglottic larynx.
AB  - Between February 1988 and December 1989, 65 patients with supraglottic cancer
      completed a course of concomitant boost radiotherapy. Cases with N3 disease, a
      Karnovsky performance score less than 70, age above 70 years, or a second primary
      cancer were not eligible for the study. Distribution of the patients was: Stage
      T1-T2 30%, T3-T4 70%, N0 68%, N+ 32%. The total dose ranged from 60 Gy to 76 Gy
      (median 66 Gy); overall treatment time ranged from 36 to 56 days with a median of
      42 days. The daily dose during the first 4 weeks was 1.8 Gy, and during the last
      2 weeks it was 1.6 Gy b.i.d. with a 4- or (after September 1988) 6-h interval.
      The clinical impression was that the early mucosal reactions were acceptable but
      more severe than after conventional treatment, with confluent membranous mucosal
      reaction being observed in 54% of the patients. Also, this reaction was
      significantly more frequent in patients treated with a 4-h interval (68%) than
      with a 6-h interval (41%) between the daily fractions. To relieve severe
      dysphagia, narcotics were required in 22% of the patients. The follow-up time
      ranged from 22 to 50 months, median 34 months. Treatment-requiring late
      complications were observed in 8 patients, and the 3-year actuarial risk was 17%
      with 95% confidence limits (6%, 27%). Two of these patients had severe
      complications: one of them required a temporary tracheostomy due to arytenoid
      edema and the other developed a laryngo-cutaneous fistula which healed after
      pharmacological treatment. Actuarial 3-year local-regional control was 59% (46%,
      71%) and 3-year actuarial crude survival 55% (42%, 67%). There was no significant
      difference in the incidence of late complications or tumor control between the
      two groups of patients treated with a 4- or 6-h interval between the daily
      fractions. This study shows that the concomitant boost regimen tried here is
      feasible, but also stresses that the interval between dose fractions should be 6
      h or more.

PMID- 8260183
TI  - The total incidence of loco-regional recurrence in a randomized trial of breast
      cancer TNM stage II. The South Sweden Breast Cancer Trial.
AB  - We studied loco-regional recurrence during follow-up (median observation time 8
      years) in 1,153 patients, who underwent modified mastectomy and were randomly
      assigned to one of the following postoperative treatments; Premenopausal
      patients: radiotherapy, cyclophosphamide, or both; Post-menopausal patients:
      radiotherapy, tamoxifen, or both. Recurrence occurred in a total of 419 patients,
      123 of whom had loco-regional recurrence with or without distant metastasis. The
      loco-regional recurrence rate was 7% in the irradiated subgroups and 17% in the
      non-irradiated subgroups, the corresponding cure rates being 43% and 58%.
      Complete remission of all local recurrence was obtained after the first treatment
      in 67% of the cases, and was persistent in 67% of them (44% overall). Complete
      remission was obtained in all patients with local recurrence who received local
      treatment only, and was persistent in 65%. Of local recurrences treated with a
      combination of surgery, radiotherapy and hormone therapy, complete response was
      obtained in 94% of the patients, and was persistent in 94% of them (88% overall).
      Complete remission of all regional recurrence was obtained after the first
      treatment in 58% of the patients and was persistent in 67% of them (39% overall).
      Postoperative radiotherapy reduced not only the total number of loco-regional
      recurrences but also the number of uncontrolled loco-regional recurrences.
      Aggressive local treatment would appear to yield both satisfactory initial
      control and, when combined with the hormone therapy, a high rate of persistent
      loco-regional control.

PMID- 8260184
TI  - Breast-conserving treatment of early breast cancer. Results in a common clinical
      trial.
AB  - Results of large prospective trials, often based on selected series and optimal
      treatment techniques, indicate that breast conserving therapy is appropriate for
      most patients with early breast cancer. Questions remain regarding the
      therapeutic outcome in common practice. We report on a series of 206 consecutive,
      unselected patients treated with current radiotherapy procedures. The Kaplan
      Meier evaluation showed 5- and 8-year survival rates (93%, 91%), distant disease
      free survival rates (87%, 85%) and local relapse-free survival rates (90%, 88%)
      that were comparable to those of the conservative arms in reported randomised
      trials and to the data from retrospective studies reported by authoritative
      institutions. However, subanalysis according to prognostic factors such as
      menopausal status, age and axillary nodal status was of limited value, due to the
      small number of cases.

PMID- 8260185
TI  - Squamous cell carcinoma antigen in serum for monitoring of head and neck and
      uterine cervical squamous cell carcinomas after radiotherapy.
AB  - Squamous cell carcinoma antigen (SCC-A) in serum was serially measured during
      follow-up of 96 squamous cell carcinoma patients (75 head and neck cancers and 21
      uterine cervical cancers), treated with radiotherapy. In 27 of the patients with
      head and neck cancer and in 12 of those with cervical cancer SCC-A had also been
      measured before radiotherapy. In this head and neck carcinoma group, the median
      level of SCC-A was 1.3 (95% CI: 1.2-1.9) ng/ml before radiotherapy and 1.4 (CI:
      1.1-1.5) ng/ml after radiotherapy. In the cervical carcinoma group, the median
      SCC-A decreased significantly (p < 0.001) from a pretreatment value of 7.5 (CI:
      3.8-26.3) ng/ml to a posttreatment value of 0.9 (CI: < 0.5-1.8) ng/ml. In the
      total group of 75 head and neck cancers 21 relapses occurred and in 4 of these
      the relapse was detected at a clinically silent stage by an elevation of serum
      SCC-A. The same was true for 4 of the 9 relapses that occurred in the total group
      of uterine cervical cancer. The study suggests that serum SCC-A may be useful for
      posttreatment monitoring of patients with uterine cervix cancer while its value
      in head and neck cancer probably is more marginal.

PMID- 8260186
TI  - Prognostic factors for local control and survival of cancer of the oral tongue. A
      retrospective analysis of 230 cases in western Sweden.
AB  - During the 19-year period from 1970 to 1988, 289 cases of squamous cell carcinoma
      of the oral tongue were diagnosed in Western Sweden. In 230 of these, treatment
      regimens and results were analysed in an attempt to define prognostic factors for
      local control and survival. Tumour stages were: T1 26%, T2 32%, T3 30% and T4
      13%. Nodal disease was seen in 32% of the patients. Sixty per cent of the
      patients had surgery, 74% external with or without combination with interstitial
      irradiation; and 32% received chemotherapy. The local control rate at five years
      was 59% (T1 66%, T2 67%, T3 44% and T4 0%). Survival at five years was 37% (T1
      61%, T2 51%, T3 19% and T4 0%). By a multivariate procedure we demonstrate that
      the tumour related variables T-category, N-category and extension to the
      tonsillar region had a significant association with survival. Extension to the
      tonsillar region, extension to the floor of the mouth and level of neck nodes
      were significantly associated with local-regional control.

PMID- 8260188
TI  - Early and late damage in the mouse bladder after radiation combined with
      cyclophosphamide or cisplatinum, evaluated by two different functional assays.
AB  - Early and late changes in the reservoir function of the mouse bladder were
      investigated after irradiation alone or combined with cisplatinum (cis-DDP) or
      cyclophosphamide (CTX). Bladder function was repeatedly assessed from independent
      assays of urination frequency and cystometry. Treatments consisted of 10-30 Gy x
      rays alone or 10-22.5 Gy combined with chemotherapy (cis-DDP 6 mg/kg i.p. or CTX
      100 mg/kg i.p.). Within 30 days after treatment, early damage was detected by
      both assays but the correlation between assays was significant only in the group
      treated with x-rays and CTX. The late response was irreversible and a correlation
      was found (p < 0.05) between urination frequency and the results of the
      cystometry assay in all treatment groups. After x-rays alone or x-rays plus cis
      DDP, the RD50 values (the radiation dose that induced a response in 50% of the
      animals) decreased with time as damage occurred. After x-rays plus CTX, maximum
      damage appeared much earlier and RD50 values tended to increase from 12 to 40
      weeks. Comparison of these RD50 values gave a dose-effect factor (the ratio
      between the RD50 doses for x-rays alone and x-ray plus drug) of 1.1 to 1.3 for
      cis-DDP in both assays. The enhancing effect of CTX on bladder reservoir function
      was greater, especially in the results of the frequency assay, as indicated by
      considerably lower RD50 values. This resulted in an estimated dose-effect factor
      of up to 2.4. In conclusion, both assays are suitable for investigating early and
      late bladder damage, although the functional defect measured is different. Both
      CTX and cis-DDP increased early and late bladder damage when combined with
      irradiation. Late damage appeared earlier in combined treatment groups than in
      mice treated with irradiation alone.

PMID- 8260187
TI  - Stage IA non-Hodgkin's lymphoma of the Waldeyer's ring. Limited chemotherapy and
      radiation therapy versus radiation therapy alone.
AB  - Seventeen patients with stage IA non-Hodgkin's lymphoma of the Waldeyer's were
      treated with radiation therapy with or without chemotherapy. All lesions were
      judged as having intermediate grade malignancy in the Working Formulation. Eight
      patients received combined treatment with three cycles of cyclophosphamide,
      doxorubicin, vincristine and prednisone (CHOP) and radiation therapy with 30 to
      40 Gy. Another 9 patients were treated with radiation therapy 40 to 60 Gy alone.
      After a median follow-up of 69 months, all 8 patients, treated with combined
      modality were alive and relapse-free, whereas 4 of the 9 treated with irradiation
      alone had relapsed. All relapses occurred trans-diaphragmatically. Two of the 4
      relapsing patients were saved, but the other two died of the disease. The 5-year
      relapse-free and cause-specific survival rates were 100% and 100% in the combined
      modality group, and 56% and 76% in the radiation therapy alone group (relapse
      free: p = 0.04, cause-specific: p = 0.16). There were no serious complications
      related to the treatment, although most patients complained of mouth dryness and
      most patients given CHOP had paresthesia. Our opinion was that the total impact
      of these two side-effects on quality of life was less pronounced after combined
      modality than after radiation therapy alone. Limited chemotherapy and radiation
      therapy seemed to be more beneficial than radiation therapy alone not only in
      relapse-free survival but also in quality of life after treatment.

PMID- 8260189
TI  - Skin infiltration within a radiotherapy portal for metastatic bladder cancer-
      case report and review of the clinical literature.

PMID- 8260190
TI  - DNA content--a prognostic factor in childhood medulloblastoma?

PMID- 8260191
TI  - Spinal cord compression in myelofibrosis--a case report.

PMID- 8260192
TI  - A profile of cerebral and hepatic carnitine, ammonia, and energy metabolism in a
      model of organic aciduria: BALB/cByJ mouse with short-chain acyl-CoA
      dehydrogenase deficiency.
AB  - Spontaneous animal models of inborn errors of metabolism are valuable tools for
      defining the pathogenesis of these disorders and also the mechanism of various
      therapeutic approaches. In the present study, we have employed BALB/cByJ mice
      with an autosomal recessive deficiency of short-chain acyl-CoA dehydrogenase
      (SCAD). These animals were characterized by a marked urinary excretion of
      ethylmalonic and methylsuccinic acids along with butyrylglycine. Using adult
      homozygous mice we have studied the basic cerebral and hepatic profile of
      carnitine, ammonia, and energy metabolism. The effects of fasting and a short
      term supplement of L-carnitine have been evaluated in comparison with control
      BALB/cJ mice. The mutant mice had low levels of acetyl-CoA and high levels of
      lactate compared to control mice. Fasting aggravated this condition by further
      decreasing acetyl-CoA and increasing lactate levels in the mutant mice. Free
      carnitine levels were significantly decreased in liver with fasting. Long-chain
      acylcarnitines were significantly lower in the brain of mutant mice. A short-term
      supplementation of L-carnitine resulted in general increases of carnitine levels
      in liver and muscle, but they still remained lower in mutant BALB/cByJ mice as
      compared to control BALB/cJ mice. L-Carnitine treatment increased cerebral CoA-SH
      levels and both hepatic and cerebral acetyl-CoA levels in mutant mice.
      Hyperammonemia which has been described frequently in acyl-CoA dehydrogenase
      deficiencies was not observed in adult BALB/cByJ mice. This could be due to a
      rapid conjugation of butyryl-CoA with glycine by an increased activity of glycine
      N-acyltransferase.

PMID- 8260193
TI  - Renal transport of glycine during glutathione replenishment in rats.
AB  - Renal transport of glycine was studied in control and glutathione-depleted rats.
      Diethylmaleate (4.0 mmol/kg body wt, ip) was used as a glutathione depletor agent
      and the studies were carried out 6 and 10 h post-diethylmaleate injection. Renal
      transport was measured in isolated rat kidney preparations by means of clearance
      techniques and in brush border membrane vesicles by a rapid filtration method.
      Tubular reabsorption of glycine, when compared to glomerular filtration rate,
      measured at different substrate tubular loads, was higher in treated kidneys.
      Tissue 14C accumulation was also higher in kidneys from diethylmaleate-treated
      animals. Studies with brush border membrane vesicles indicated that glutathione
      depletion induced higher sodium-dependent glycine uptake in contrast with control
      preparations. This adaptation was not associated with an increment in either tau
      glutamyltransferase activity or in protein concentrations. These results could
      explain in part the replenishment of GSH cellular levels in glutathione-depleted
      kidneys by means of higher transport capacity for glycine (a glutathione
      precursor) which was maintained even when GSH levels were restored.

PMID- 8260194
TI  - Four new mutations in the ornithine transcarbamylase gene.
AB  - We characterized four new mutations in the ornithine transcarbamylase (OTC) gene
      in three male infants who died from acute neonatal hyperammonemia and one male
      infant with late onset disease. OTC enzymatic activity was undetectable in the
      livers of the three neonates, whereas residual enzymatic activity was present in
      the fourth patient. All 10 exons of the OTC gene were amplified by the polymerase
      chain reaction (PCR) from genomic DNA of the four patients. The amplified DNA was
      screened for abnormal gel electrophoretic migration patterns via single-strand
      conformational polymorphism (SSCP). One patient showed an abnormal SSCP pattern
      of exon 8 and exon 9, a second patient had an abnormal exon 6, a third had an
      abnormal exon 9, and the fourth patient revealed an abnormal exon 3. Sequencing
      of the abnormal exons revealed that the first patient had a deleterious mutation
      in exon 9 consisting of a G-->T transversion in codon 310 causing a Glu-->stop
      coding change. The abnormal exon 8 of this patient contained a common
      polymorphism consisting of an A-->G transition in codon 270 resulting in Gln-
      >Arg code change. The abnormal exon 6 of the second patient contained an A-->G
      transition in codon 183 causing a Tyr-->Cys change. Exon 9 of the third patient
      contained a deletion of a thymine nucleotide (base 882) resulting in a shift of
      the reading frame and a code for premature termination 28 codons downstream. The
      fourth patient with a "milder" clinical presentation had an A-->T transversion in
      exon 3 (codon 88) causing a Lys-->Asn change.

PMID- 8260195
TI  - The dopamine D2 receptor (DRD2) as a major gene in obesity and height.
AB  - Dopamine plays a major role in the regulation of appetite and growth hormone.
      Dopaminergic agonists suppress appetite and dopamine D2 receptor antagonists
      enhance it. We examined the hypothesis that allelic variants of the DRD2 locus
      may be associated with weight and height. Sarkar and Sommer described two DRD2
      polymorphisms that could be haplotyped by PCR. For weight, the mean Z score
      (National Center for Health Statistics) for 208 subjects without haplotype 4 was
      0.086 versus 0.557 for 280 subjects with haplotype 4, P = 0.0003. Two separate
      sets of subjects were studied and these results were significant for both,
      providing an internal replication. For height, the mean Z score for 164 subjects
      without haplotype 4 was 0.1677 versus 0.6885 for 219 subjects with haplotype 4, P
      < 0.00001. These and other data suggest that the 4 haplotype is in linkage
      disequilibrium with allelic variants of the DRD2 gene that play a major role in
      the regulation of weight (obesity) and height, and may serve as a risk factor in
      late-onset non-insulin-dependent diabetes mellitus (NIDDM).

PMID- 8260196
TI  - Identification of Gaucher disease carriers: glucocerebrosidase antigen and DNA
      analysis.
AB  - Detection of Portuguese carriers for Gaucher disease with urine samples as a
      source of enzyme was carried out using an immunological procedure employing an
      anti-glucocerebrosidase monoclonal antibody and by DNA analysis for the presence
      of the two glucocerebrosidase mutations most frequently found in Portuguese
      Gaucher patients. Patients, obligate and putative carriers, and individuals
      unrelated to patients were analyzed. It was found that the vast majority of
      carriers for the two tested mutations (N370S and L444P), as well as obligate
      carriers for as yet unidentified mutations, could be distinguished from control
      subjects with this relatively easy and economic immunological procedure.
      Furthermore, results obtained for control subjects suggested a high frequency of
      carriers for the N370S mutation in the Portuguese population. It is concluded
      that this procedure may be useful in mass screening for carrier detection prior
      to DNA analysis, particularly in the study of non-Ashkenazi populations in which
      a significant number of mutations associated with Gaucher disease remain
      unidentified.

PMID- 8260197
TI  - The effect of diabetes and dietary ascorbate supplementation on the oxidative
      modification of rat lens beta L crystallin.
AB  - The level of characteristic markers of protein oxidative modification (tryptophan
      oxidation and sulfhydryl group loss as well as carbonyl and bityrosine formation)
      and glycation (AGEP formation) have been measured in beta L crystallin purified
      from the lenses of control, diabetic, and ascorbate-supplemented diabetic
      animals. These markers were also determined following the application of an in
      vitro graded oxidative insult. Prior to the application of stress, diabetic lens
      crystallins, in comparison with control, exhibited a higher content of bityrosine
      and AGEPs, a lower level of nonoxidized tryptophan, and a loss of sulfhydryl
      groups. After exposure to the oxidative insult there was a stress-proportional
      increase of the parameters in all beta L crystallins, irrespective of their
      source. The effects were most pronounced in the diabetic, in which the already
      elevated indicators of oxidative damage were further increased. Dietary
      supplementation of the diabetic group with ascorbate had a marked effect in
      preventing beta L crystallin modification in vivo, alleviating the loss of
      sulfhydryl groups and the oxidation of tryptophan, partially preventing the
      formation of AGEP and carbonyl groups, but not affecting the formation of
      bityrosine. Supplementation also inhibited the increase in susceptibility of
      diabetic beta L crystallin to in vitro oxidative stress, preventing sulfhydryl
      group loss as well as carbonyl and AGEP group formation. The results are
      discussed in relation to the proposal that diabetes renders lens crystallins more
      susceptible to oxidative stress and that this may be a causative factor in
      cataractogenesis. The possible role of ascorbate in the inhibition, or
      attenuation, of cataractogenesis is examined.

PMID- 8260198
TI  - A casein kinase type II (CKII)-like nuclear protein kinase associates with,
      phosphorylates, and activates topoisomerase I.
AB  - Topoisomerase I (Topo I) is involved in many cellular functions that involve
      unwinding of supercoiled DNA, such as transcription and replication. Topo I is
      also the target of autoimmune antibodies in progressive systemic sclerosis
      (scleroderma), and abnormal regulation of Topo I may influence the excessive
      production of collagen found in scleroderma. Topo I is phosphorylated in vivo at
      serine residues and, in vitro, the activity of Topo I is increased by
      phosphorylation by casein kinase type II (CKII) and protein kinase C (PKC). In
      this study, a protein kinase activity from rat liver nuclei is shown to copurify
      with Topo I during Bio-Rex 70 cation exchange chromatography. The kinase can
      phosphorylate Topo I at serine residues, resulting in a threefold increase in
      topoisomerase activity. A relatively tight association between this kinase and
      Topo I is demonstrated by the ability to coprecipitate the kinase with
      scleroderma autoimmune anti-Topo I antibodies. The kinase activity is similar to
      CKII since it is Ca2+ and cyclic nucleotide independent, it can utilize either
      ATP or GTP as phosphate donor, and it can phosphorylate casein and phosvitin, but
      not histones. However, unlike typical CKII, the Topo I-associated kinase could
      utilize Mn2+ almost as well as Mg2+, it is not stimulated by polyamines, and it
      does not appear to undergo autophosphorylation. In conclusion, we demonstrate
      that rat liver Topo I is relatively tightly associated with a CKII-like protein
      kinase that can phosphorylate and activate Topo I. These findings provide
      corroborative evidence that CKII, or a CKII-like protein kinase, is a physiologic
      regulator of Topo I.

PMID- 8260199
TI  - Could non-insulin-dependent diabetes mellitus be attributable to a deficiency of
      FAD-linked glycerophosphate dehydrogenase?
AB  - In 12 out of 32 non-insulin-dependent diabetic subjects, the activity of FAD
      linked glycerophosphate dehydrogenase in T lymphocyte homogenates was abnormally
      low when measured by both a colorimetric and radioisotopic procedure. A
      comparable situation characterized by a deficient activity of FAD-linked
      glycerophosphate dehydrogenase in both the colorimetric and radioisotopic assays
      was only observed once among 26 other subjects including 11 healthy volunteers, 9
      non-diabetic patients, 5 type-1 (insulin-dependent) diabetics, and 1
      pancreatectomized diabetic. By analogy, it is speculated that an impaired
      activity of FAD-linked glycerophosphate dehydrogenase in the insulin-producing
      pancreatic B-cell could represent a far-from-uncommon contributive factor in the
      pathogenesis of non-insulin-dependent diabetes mellitus.

PMID- 8260200
TI  - Molecular confirmation of alpha 1-antitrypsin genotypes in newborn dried blood
      specimens.
AB  - Deficiency of alpha 1-antitrypsin (alpha 1AT), a common hereditary disorder of
      Caucasians, is associated with an increased risk for early-onset chronic
      obstructive pulmonary disease and childhood liver dysfunction. The two most
      common deficiency variants, PiS and PiS, are both single base-pair substitutions
      causing amino acid modifications, although neither mutation creates or destroys a
      naturally occurring restriction site. Dried blood specimens (DBS) submitted to
      the New York State Department of Health for mandated newborn screening tests were
      tested for alpha 1AT activity using a fluorometric elastase inhibition assay. A
      second DBS from specimens determined to be alpha 1AT deficient was phenotyped on
      an agarose isoelectric focusing gel. Genotypic confirmation was performed by
      amplifying, directly from a DBS, the regions of the DNA containing the S and Z
      mutation. The Z mutation was analyzed with a modified primer designed to create
      an artificial restriction site in the normal allele. TaqI digestion produces two
      bands, a 157- and a 22-bp fragment. The single base substitution in PiS
      individuals eliminates this TaqI restriction site, thus showing the same 179-bp
      fragment before and after digestion. A primer mismatch placed close to the S
      mutation creates a restriction site in the normal allele, producing a 100-bp
      product after TaqI digestion. The restriction site is abolished in individuals
      that carry the S mutation, with a 121-bp product observed before and after
      digestion. Of 11,081 specimens screened, 3 PiS neonates, all Caucasian, were
      detected by these methodologies for an estimated incidence of 1:2019 in the
      Caucasian or 1:3694 in the general population in New York State.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260201
TI  - [DNA-based diagnosis of Angelman syndrome and Prader-Willi syndrome].
AB  - A molecular-genetic study was performed in 61 patients with Angelman syndrome
      (AS) and 14 patients with Prader-Willi syndrome (PWS). Southern blot analyses
      and/or PCR-mediated dinucleotide repeat polymorphism (DNRP) analyses revealed
      that 67% of AS patients have DNA deletions ranging from D15S9 to D15S12 loci. An
      exception was 3 sib cases whose deletion involved only 2 loci, D15S10 and GABRB3.
      The parental origin of the deletions in AS patients were exclusively maternal. No
      uniparental disomy (UPD) was found in our AS patient series, suggesting that UPD
      in AS is infrequent than that in PWS. Molecular deletions were observed in 6 of
      the 14 PWS patients. In order to develop a simple, reliable DNA-based diagnostic
      method, I adopted PCR-mediated DNRPs as genetic markers for the detection of
      deletions and/or parental origin of chromosomes 15 in AS and/or PWS patients.
      This method gave useful diagnostic information in 33 (89%) of 37 AS patients and
      12 (86%) of 14 PWS patients, indicating no big difference from the information
      obtained with Southern blot analysis. Furthermore, since this DNRP method dose
      not require radioisotopes, it may be a first-choice, alternative way when
      diagnosing AS or PWS patients.

PMID- 8260202
TI  - [Estimation of primary focus using an averaging of spikes in epileptic children
      with multiple foci].
AB  - To estimate the primary focus in 17 epileptic children with multifocal spikes,
      simultaneous averaging of spikes in 16 channels was performed. At first, EEG was
      recorded on EEG-video monitoring tape. Then, the computer sampled the data every
      5 msec through an A-D converter, and stored the corresponding digital values. We
      used the top of the spike as a trigger point, and averaged 7 to 50 spikes in each
      lead. The primary focus and areas propagated from it were determined from the
      latency between the averaged spikes in different leads. We defined multiple foci
      when morphologically different averaged spikes were independently present in
      different leads. The averaging method could narrow the areas with spike
      discharges in 16 of 17 patients, and define a single focus in 6 patients.
      Furthermore, the single or unilateral foci in averaged data were compatible with
      the site estimated from lateralizing signs, such as lateral version of head and
      eyes in 3 of 8 patients. The other 5 patients showed independent bilateral foci,
      one of whom received focal resection of right anterior frontal lobe which was
      responsible for ictal symptoms and seizure discharges. Since then, seizures and
      right frontal epileptic discharges have not been observed but the spikes in left
      anterior frontal lobe have been left. These findings suggest that averaging of
      epileptic discharges is useful for determination of primary focus and for
      differentiation of true multiple foci from secondary propagation.

PMID- 8260203
TI  - [The relationship between P300 latencies, and WISC-R and Wechsler memory scale
      results in epileptic children].
AB  - Auditory event-related potentials (ERPs) were recorded in 35 epileptic children
      of 9 to 13 years of age, and compared with conventional test batteries of
      cognitive functions. ERPs were elicited with the auditory oddball paradigm.
      Corrected P300 latencies showed an inverse correlation with the total score (IQ)
      of WISC-R and that of the Wechsler memory scale (WMS). A strong inverse
      correlation was also observed with specific items of these test batteries, as
      follows; "comprehension", "picture completion" and "coding" in WISC-R, and
      "associated learning", "digit span", "visual reproduction", "mental control",
      "orientation" and "information" in WMS. These findings suggested that the
      prolongation of P300 latencies in epileptic children are related with the
      impairment of cognitive functions. The P300 latency is correlated with a
      characteristic kind of cognitive function; "simple recognition", "short term
      memory" and "easy judgement".

PMID- 8260204
TI  - [A follow-up study of idiopathic status convulsivus in childhood].
AB  - We studied the prognosis of twenty-five idiopathic status convulsivus (SC)
      patients. They were neurologically normal before the onset, and had the first
      episode of idiopathic SC, defined as a seizure with a duration of longer than 30
      minutes, febrile in 18 cases and afebrile in 7 cases. We excluded acute
      encephalitis, encephalopathy and past history of epilepsy in all patients. The
      age of the first SC ranged from 3 months to five years and 3 months (median; 1
      year and 9 months). They were followed successively for a period of 3 years to 15
      years and two months (median 8 years and 7 months). The final diagnosis was
      epilepsy in 7 cases, epilepsy border in 11 cases, and febrile convulsion in 7
      cases. One patient showed a remarkable learning disability, but no patients had
      psychomotor retardation. Antiepileptic drugs were given 24 patients, all of whom
      were well controlled, including 17 cases with successful withdrawal of these
      drugs. In our febrile convulsion cases, there was no more than one risk factor
      for the development of epilepsy (Awaya). The prognosis of febrile SC cases was
      favorable.

PMID- 8260205
TI  - [Severely handicapped children and its relationship with perinatal medical care].
AB  - We studied the etiology for sixty-eight severely handicapped children aged
      between 3 and 6 years, who were born in the Himeji city and the environs (9,900
      live births/year). The prevalence was around 1.7/1,000 live births. The factors
      of their handicaps were as follows: congenital 25%; perinatal 40%; neonatal
      period 21%; and unknown onset 15%. Thirty-six patients out of 54 (67%) were
      admitted to neonatal intensive care unit (NICU) and visited the Center for
      neurological follow up immediately after their discharge. The high frequency of
      patients from NICU, compared with previous reports, might be due to a cooperative
      network between NICUs and the Center with medical support for handicapped
      children in this area.

PMID- 8260206
TI  - [Cerebral palsy in children and its relationship with perinatal medical care].
AB  - We studied the etiology of 76 children with cerebral palsy (CP) aged 3 to 6
      years, who visited the Himeji City Center for the Handicapped for neurological
      follow up. The patients for this study composed of 30 cases with severe handicap.
      8 cases of CP with mental retardation and 10 cases of CP without mental
      retardation. Nine cases of CP had congenital anomalies of central nervous system,
      of which 8 cases showed severe handicap. Main perinatal factors were asphyxia,
      dyspneic condition needed for mechanical ventilation, prolonged apneic spells,
      and hyperbilirubinemia. All full-term birth children were accompanied with
      asphyxia, in which 43% had intracranial hemorrhage. A cooperative network between
      neonatal intensive care unit and an institute for the handicapped is essential
      for the care of infants with cerebral palsy.

PMID- 8260207
TI  - [Pathophysiology of carbohydrate-deficient glycoprotein syndrome-
      neuroradiological and neurophysiological study].
AB  - Neuroradiological and neurophysiological studies were done in two male siblings
      with carbohydrate-deficient glycoprotein syndrome (CDGS) (case 1 and 2) and one
      male second cousin presumed with CDGS (case 3). Case 1 and 2 had abnormality of
      epileptic discharge in EEG. Case 1 had MCV in the lowest normal range, giant SEP
      was observed in SSEP in case 1 and low voltage of P 14 in case 3. Case 1 had low
      voltage of wave V in ABR and case 3 had low voltage of wave V on one side and no
      response on the other side. The all cases showed the normal pattern for VEP and
      MEP. All showed cerebellar hypoplasia and various degree of pontine hypoplasia on
      MRI. SPECT showed hypoperfusion in cerebellum, brainstem and left centroparietal
      region in case 1. In CDGS we found the hypoplasia of cerebellum and pons in
      common, but it was suggested that CDGS might have the heterogeneity of
      pathophysiology on the basis of various neurological abnormalities.

PMID- 8260208
TI  - [An investigation of medical circumstances of the long-term hospitalized severely
      mentally and physically handicapped children in Sapporo district].
AB  - The author investigated medical circumstances of the severely mentally and
      physically handicapped children who needed to be treated for more than one month
      at general hospitals in Sapporo district using a questionnaire method followed by
      a direct observation. Fifty patients were identified and their chronological ages
      distributed from 5 months to 19 years old. The mean period of hospitalization was
      approximately 2 years. They could be roughly divided into two groups; high risk
      infants for severely mental and physical handicap; and the most severely mentally
      and physically handicapped teens needing hospital treatment for their lives.
      Etiology was congenital in 38% (CNS malformations, neuromuscular diseases, etc.),
      acquired in 36% (hypoxic brain damage due to accidents, CNS infections, etc.) and
      perinatal in 26% (all hypoxic ischemic encephalopathies). More than 90% of the
      patients showed abnormal brain CT scan and 20% had visual and/or auditory
      disturbances. A half of them needed artificial ventilation supports and/or
      tracheal cannulation. More than 60% received tube feeding therapies. From this
      evidence, it is considered that the long term hospitalized severely mentally and
      physically handicapped children have severe brain dysfunction which needs high
      medical technology and professionals. It seems that a little remedial supports to
      them is done in general hospitals at present in Sapporo district. Comprehensive
      treatment will hopefully be done for them in the near future.

PMID- 8260209
TI  - [MRI hippocampal volumetric measurements in benign childhood epilepsy with
      centrotemporal spike(s) and temporal lobe epilepsy of childhood onset].
AB  - Benign childhood epilepsy with centrotemporal spike(s) (BCECT) is characterized
      by rolandic discharges (RD) on EEG. As the origin of RD, the lower rolandic
      cortex was proposed by Lombroso, but recently the hippocampus was proposed by
      some reports, based on the character of RD or the pharmacological effects of
      anticonvulsants. On the other hand, MRI hippocampal volumetric measurements
      revealed the relationship between the hippocampal atrophy and EEG foci in
      intractable temporal lobe epilepsy (TLE) of adults, but there are a few reports
      of the hippocampal volumetric study in children. Therefore, in this paper, we
      reported about MRI hippocampal volumetric measurements in BCECT and TLE of
      childhood onset. The statistical examination was performed by t-test. MRI
      hippocampal volumetric measurements were performed in 27 cases with BCECT (6-19
      years, 9.9 +/- 2.7 years, 11 males, 16 females), 22 cases with TLE (5-22 years,
      12.9 +/- 5.5 years, 15 males, 7 females) and 17 normal control subjects (6-15
      years, 10.4 +/- 2.7 years, 10 males, 7 females). The age was not significantly
      different among the 3 groups. The clinical course of TLE group was significantly
      longer than BCECT group, but the onset age of epilepsy was not significantly
      different between the 2 groups. The hippocampal volume and the right-side minus
      left-side volume were not significantly different in 3 groups, but these values
      of TLE were more scattered than the others. There was no abnormal signal
      intensity in hippocampus on MRI, or no specific abnormality in the surrounding
      structures in 3 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260210
TI  - [Methylmalonic acidemia with bilateral MRI high intensities of the globus
      pallidus].
AB  - We report a patient with methylmalonic acidemia who developed an acute
      extrapyramidal disorder after severe ketoacidosis. The neurologic findings
      resulted from bilateral destruction of the globus pallidus. A 10-year-old girl
      was the term product of an uncomplicated pregnancy and delivery. Poor feeding and
      vomiting were noted after one month. She was hospitalized at 6 months of age with
      vomiting, coma and tachypnea. Analysis of urinary organic acids revealed a
      massive amount methylmalonic acid. She was not vitamin B 12-responsive and was
      maintained on a low-protein diet. At 33 months of age, she was able to walk and
      speak, but she developed acute severe ketoacidosis. Involuntary movements and
      spastic paraplegia became evident two days after admission. Subsequently, the
      patient has had metabolic ketoacidosis once or twice a year. Her intelligence
      quotient was 47. Neurologic examination revealed spastic paraplegia and
      generalized hypotonicity with mild dystonia. Some relief from dystonic symptoms
      has been obtained through the use of L-dopa. A brain CT scan at 5 years of age
      disclosed bilaterally symmetric lucencies of the globus pallidus. T2-weighted
      brain MRI at 8 years of age showed bilateral symmetric high intensities of the
      globus pallidus.

PMID- 8260211
TI  - [A case of tyrosinemia type II with convulsion and EEG abnormality].
AB  - A 10-year-old boy with palmoplantar hyperkeratosis and keratitis was reported.
      His physical development was normal and mental development was lower limit. He
      had also convulsions with low grade fever several times, and his EEG showed
      paroxysmal discharges. The plasma levels of phenylalanine and tyrosine were 5 to
      10 times higher than those of controls. Tyrosinemia II was diagnosed on the low
      level of cytosol tyrosine aminotransferase in biopsied liver. The cases of
      tyrosinemia II were reviewed on the symptoms of the central nervous system. Two
      of twelve cases had convulsions. Adult cases demonstrated nystagmus, tremor,
      ataxia, and convulsion. Hyperkeratosis and corneal lesions were characteristic in
      symptoms of tyrosinemia II, but attention should be paid to the symptoms of the
      central nervous system.

PMID- 8260212
TI  - [A case of benign childhood epilepsy with centrotemporal spike diagnosed by a
      seizure during polysomnography and clinical and EEG follow-up].
AB  - A healthy boy who had showed no evidence of cerebral lesions developed epileptic
      seizures resembling grand mal during nocturnal sleep at the age of 9 years and 2
      months. Interictal EEG showed diffuse sharp waves that were maximal in the right
      centroparietal area and recurred at short intervals. Polysomnography for one
      night was performed when the patient was 9 years and 11 months old. The values of
      sleep variables (percentage of sleep period time for each sleep stage, sleep
      latency, REM density) were within normal limits. Interictal sharp waves appeared
      most frequently in the stages 3 and 4, and least in the stages REM and W. Partial
      seizure of the left face occurred with impaired consciousness in the stage 2 at
      around 5 a.m. On the ictal EEG, a low-voltage fast discharge was initiated in the
      right frontal area, followed by a diffuse rhythmic discharge of high voltage at 5
      6 Hz, which was associated with a clinical seizure. The seizures completely
      ceased within one month after the polysomnography. Interictal sharp waves that
      migrated to the centrotemporal or midtemporal area disappeared at the age of 15
      years and 9 months. The patient is now 19 years and 5 months of age. Although his
      interictal EEG and clinical seizures were atypical, we diagnose his disease as
      benign childhood epilepsy with centrotemporal spike based on the polysomnographic
      findings and the clinical and EEG follow-up.

PMID- 8260213
TI  - [A case of myoclonic encephalopathy of infancy associated with cytomegalovirus
      infection].

PMID- 8260214
TI  - [Cocoa therapy for zinc deficiency in severely handicapped children with tube
      feeding].

PMID- 8260215
TI  - Assessment at last.

PMID- 8260216
TI  - Bronchodilators: wrong for the lung in the long run?

PMID- 8260217
TI  - Prevalence of hearing loss among people aged 65 years and over: screening and
      hearing aid provision.
AB  - The aim of this study was to assess the prevalence of hearing loss among people
      aged 65 years and over and to offer hearing aids where necessary. The study was
      carried out in a large health centre practice in Birmingham with a computerized
      record system. All patients aged 65 years, and a 20% random sample of patients
      aged 66 years and over were invited for interview. They were questioned about
      hearing loss and examined audiometrically. All patients with a hearing loss in
      the better ear of 35 decibels or more over the speech frequencies (0.5-4 kHz)
      were offered a hearing aid. A total of 322 patients attended (72% of those
      invited) and of these 34 patients already had a hearing aid. A further 142
      patients were identified for whom an aid was recommended and 69 of these
      accepted. The acceptance rate was higher among men than women (57% compared with
      43%). Sixty one patients (19% of those screened) had an asymmetrical hearing loss
      and of these 24 required consultant assessment; none had serious underlying
      pathology. There is a large unmet need for hearing aid provision. Simple
      audiometric assessment in health centres provides an opportunity to meet this
      need.

PMID- 8260218
TI  - Work patterns of general practitioners before and after the introduction of the
      1990 contract.
AB  - A questionnaire survey was undertaken to examine the work patterns of general
      practitioners before and after the introduction of the 1990 contract. A total of
      408 and 697 general practitioners responded to the questionnaire in 1989 and
      1991, respectively (response rates of 47% and 82%). In 1991 general practitioners
      reported spending significantly more evenings on paperwork than in 1989 and
      significantly more reported being exhausted or stressed at the end of five or
      more working days. General practitioners were significantly less likely to work
      four or more sessions per week outside the practice in 1991 than in 1989. There
      was no difference between 1989 and 1991 in the number of surgeries carried out
      per week or the number of nights spent on call in a month. In 1991 there was no
      correlation between the Jarman index allocated to a practice principal and the
      numbers of surgeries per week, sessions worked outside the practice per week,
      nights on call per month, weekdays exhausted or stressed, or evenings each week
      spent on paperwork. Older doctors in 1991 were significantly more likely to work
      12 or more nights on call per month, to spend more time doing paperwork in the
      evenings and more likely to report exhaustion than younger doctors. Women doctors
      in 1991 were significantly more likely to report doing 10 or more surgeries per
      week than their men colleagues. It has become more common for general
      practitioners to complete paperwork at home and report exhaustion or stress since
      the introduction of the 1990 contract.

PMID- 8260219
TI  - General practice workload during normal working hours in training and non
      training practices.
AB  - The aim of this study was to design and test a form to review workload in
      training and non-training practices. The study was conducted in the Oxford,
      Reading and Milton Keynes districts over a period of one week and involved 31
      training and 21 non-training practices consisting of 156 and 66 doctors,
      respectively. Doctors in training practices (excluding trainees) spent a mean of
      one hour less per week in contact with their patients than doctors in non
      training practices. Doctors in training practices spent approximately the same
      time per week on administration as those in non-training practices, one hour more
      in both meetings and non-practice work and almost two hours more in training and
      studying. The mean total practice workload per doctor in training practices was
      two hours more than in non-training practices and, when non-practice work was
      included, the difference increased to three hours. Compared with other doctors,
      trainees saw fewer patients in the surgery, in clinics and on visits, but spent
      more time on studying and training. This study produced broadly similar results
      to previous surveys, although doctors in the present study saw fewer patients
      each week and spent more time with each patient than in other studies.

PMID- 8260220
TI  - Working with community mental health professionals: a survey among general
      practitioners.
AB  - Links between general practitioners and mental health professionals, such as
      counsellors, psychiatrists, community psychiatric nurses, clinical psychologists
      and social workers, are increasing in number and type. The aim of this survey was
      to elicit general practitioners' attitudes to these workers, comparing those with
      a link with a mental health worker and those without. General practitioners in
      two district health authorities were surveyed and a response rate of 70% was
      obtained. General practitioners linked to a mental health professional were more
      likely to have made a referral to that service in the previous three months and,
      on the whole, were more satisfied with that service. The commonest problem
      reported by respondents was the length of waiting lists. Regarding liaison with
      social workers, inadequate feedback and difficulty with contact were the problems
      mentioned most by doctors. A number of general practitioners expressed a desire
      for closer contact with all these mental health services. While caution is
      required in ascribing causality to these relationships, it is clear that a closer
      working relationship between general practitioners and mental health workers is
      productive and is valued by general practitioners. The challenge for policy
      makers is to structure mental health provision in such a way that more general
      practitioners are able to benefit than at present.

PMID- 8260221
TI  - Hyperventilation in patients with recurrent functional symptoms.
AB  - In view of the similarity between the reported effects of hyperventilation and
      recurrent functional symptom presented in primary care, a study was undertaken to
      establish whether such symptoms are attributable to hyperventilation. Twenty
      patients with two or more recurrent functional symptoms which their doctors found
      difficult to diagnose or treat, and 30 controls, were studied using symptom
      questionnaires and a series of hyperventilation provocation tests during which
      the partial pressure of carbon dioxide (PCO2) and symptoms were recorded. Sixteen
      cases (80%) had unexplained breathlessness compared with two of the controls
      (7%). All of the cases recognized familiar functional symptoms during provoked
      hyperventilation, and in 16 (80%), these included primary physical symptoms; only
      23% of the controls recognized any previously experienced symptom. Considerable
      overlap of PCO2 values between groups meant that absolute values of PCO2 were not
      useful in differentiating between groups, but cases were more likely than
      controls to have a PCO2 of less than 4 kPa at rest, three minutes after
      hyperventilation, or during mental stress (75% of cases fulfilled one or more of
      these criteria versus 40% of controls). This is the first study in primary care
      to examine the effect of hyperventilation in a group of patients with multiple
      somatic symptoms. The findings have implications for the recognition and
      management of such patients.

PMID- 8260222
TI  - Management of urinary incontinence in women.
AB  - Control of micturition is a complex physiological and anatomical process which
      often fails in women. The sequelae of urinary incontinence in women range from
      inconvenience to social and psychological stigmatization. Surprisingly, many
      women are tolerant of often quite severe sequelae, despite a range of management
      techniques that exist to alleviate or cure incontinence. Some of the more
      successful techniques are well suited to general practice management and can be
      carried out by the patient under the supervision of her doctor, district nurse,
      practice nurse or midwife. This paper reviews the physiology of micturition,
      stress urinary incontinence and incontinence caused by detrusor instability, and
      the management techniques available to alleviate or cure the problem.

PMID- 8260223
TI  - Summative assessment: a pilot project in the west of Scotland.
AB  - In the autumn of 1991 the Committee in General Practice of the west of Scotland
      region appointed a working party to investigate the possibility of developing a
      credible, valid and reliable programme of summative assessment for general
      practitioner trainees. The working group formulated a four-part package
      consisting of a multiple true-false paper, a trainee audit project, the trainers'
      judgement, and analysis of videotaped consultations. The reasons for the use of
      this selection of methods are discussed. It is suggested that a summative
      assessment process for trainees should make use of the trainers' considerable
      knowledge of the trainee, have an external component, be criterion referenced,
      have an element of continuous assessment, and involve direct assessment of
      clinical competence. A pilot study of assessment of clinical competence using
      videotapes of routine trainee consultations by 25 volunteer general practitioner
      assessors is described. A rating instrument for use in differentiating the
      competent from the not yet competent trainee is discussed. The working group and
      the group of videotape assessors came to the provisional conclusion that the use
      of videotaped consultations may be a valid and feasible method of assessing the
      competence of general practitioner trainees as part of a balanced summative
      assessment programme.

PMID- 8260224
TI  - Rubella antibody screening.

PMID- 8260225
TI  - Psychological consequences of hypercholesterolaemia.

PMID- 8260226
TI  - Surgical treatment for early breast cancer: should the patient decide?
AB  - Conservative surgery followed by a course of radiotherapy has been shown to be as
      effective as mastectomy in terms of survival and disease-free interval. This has
      led to an increase in the number of surgeons who undertake conservative surgery
      for early breast cancer. However, some studies have shown that, when offered a
      choice of surgery, some women elect mastectomy. Such results highlight the need
      for patients to be fully involved in the decision made about surgery, especially
      in the circumstances where there is more than one surgical option and a choice of
      surgery can be offered.

PMID- 8260227
TI  - Facilitating phase I trials of products of recombinant DNA technology.

PMID- 8260228
TI  - Firmer evidence on the value of breast screening--the Swedish overview.

PMID- 8260229
TI  - Improvement of the diagnosis of the cause of pleural effusion in patients with
      lung cancer by simultaneous quantification of carcinoembryonic antigen (CEA) and
      neuron-specific enolase (NSE) pleural levels.
AB  - Carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) level
      determinations were carried out by radioimmunoassay in pleural fluid and plasma
      samples obtained from 24 patients with malignant pleural effusions and 18
      patients with non-malignant pleural effusions, and compared to cytological and
      pathological results. Using a pathological cut-off level of 25 ng/ml for CEA and
      8 ng/ml for NSE, we demonstrated that, in the diagnosis of the malignant nature
      of pleural effusions, the simultaneous quantification of CEA and NSE in pleural
      fluid possesses better discriminative values than the simultaneous quantification
      of both markers in plasma or the separate quantification of each marker, in
      pleural fluid and in plasma.

PMID- 8260230
TI  - Age and prognosis of non-small cell lung cancer. Usefulness of a relative
      survival model.
AB  - The aim of our study was the comparative evaluation of a relative survival model
      and a Cox model to determine the prognostic factors of survival for patients with
      surgically cured non-small cell lung cancer (NSCLC). We focused particularly on
      the exact role of age in this survival. 156 patients treated between 1975 and
      1988 were studied. Both univariate and multivariate analyses were performed,
      using the actuarial method and the Cox model for crude survival and the Hakulinen
      model for relative survival. This study confirmed the poor prognosis of NSCLC,
      even if a curative surgical procedure has been possible, with a 5-year survival
      of 48% for stage I tumours but only 6% for stage III tumours. The most
      significant prognostic factor was the postsurgical TNM staging. The relative
      survival method of Hakulinen dismissed age as a significant prognostic factor.
      Our study underlines the usefulness of relative survival methods which should be
      more frequently employed to allow comparisons between series of different origin
      and to set up multicentre therapeutic trials.

PMID- 8260231
TI  - Mitoxantrone, folinic acid, 5-fluorouracil and prednisone as first-line
      chemotherapy for advanced breast carcinoma. A phase II study.
AB  - The purpose of this prospective clinical trial was an attempt to find an
      effective and relatively non-toxic schedule for patients with metastatic breast
      cancer who decline to receive aggressive cytotoxic chemotherapy. A total of 36
      patients with disseminated breast cancer were treated with mitoxantrone 8 mg/m2
      intravenously (i.v.) day 1, folinic acid 400 mg/m2 in a 2-h i.v. infusion with 5
      fluorouracil 500 mg/m2 as an i.v. bolus 1 h later, days 1 and 8 at 3-week
      intervals plus prednisone 20 mg/m2 orally daily with diminishing doses over
      several weeks. Objective regressions were observed in 24/36 (67%) patients, 9
      being complete (25%). Responses were seen at all disease sites, mainly
      pleural/lung, bone and liver. The median duration of response was 8 months (range
      4-25+) and the median survival 12 months (range 3-26+). Myelosuppression, mainly
      leucopenia and thrombocytopenia, was the major toxicity but without
      complications. Other toxicities included mild or moderate nausea and/or vomiting
      (50%), stomatitis (33%) and diarrhoea (11%). Alopecia was minimal. No cases of
      cardiotoxicity were detected. The substantial response rate obtained with this
      relatively well tolerated regimen against advanced breast cancer warrants its
      assessment in a larger number of patients.

PMID- 8260232
TI  - "Occult" papillary carcinoma of the thyroid: a questionable entity.
AB  - A series of 72 cases of "occult" thyroid papillary cancer, i.e. tumours of less
      than 1.5 cm in diameter, was analysed. The patients--26 males and 46 females-
      were treated surgically, 25 by lobectomy and isthmusectomy and 47 by total
      thyroidectomy. In 51 cases nodal neck dissection was performed, bilateral in 2
      cases. 9 thyroidectomised patients received radiometabolic therapy. Hormone
      therapy (T4) was continuously administered to 57 patients. The median duration of
      follow-up was 99 months (60-189). All the patients were alive (except one who
      died from other causes) and free of disease at last control. No relapses in the
      thyroid were observed in the conservatively treated patients. 2 patients of the
      47 radically operated upon subsequently presented nodal metastasis and underwent
      neck dissection. The so-called "occult" thyroid papillary cancer does not differ
      from other papillary cancers with respect to morphological, clinical and
      prognostic factors--it differs only in size. Considering occult papillary tumours
      as an entity is questioned in this paper.

PMID- 8260233
TI  - Expression of sialyl-Tn antigen is correlated with survival time of patients with
      gastric carcinomas.
AB  - Expression of sialyl-Tn antigen (STN) was examined by an immunohistochemical
      method in 85 primary gastric carcinomas. The STN expression occurred in 53
      (62.4%) cancers, and the positive staining was correlated with degree of gastric
      wall and lymph vessel invasion, lymph node metastasis, and stage of tumour. Five
      year survival rates of patients with STN-positive cancers (47.2%) were
      significantly lower than those with STN-negative cancers (84.4%) (P < 0.01), and
      patients with STN-positive cancers at stage III and stage IV had a worse
      prognosis. In the cancers with serosal invasion, patients with STN-positive
      cancer disclosed a significantly poorer prognosis than those with STN-negative
      cancers (P < 0.01). Therefore, it is suggested that a careful follow-up study and
      intensive postoperative therapy are needed for patients with advanced gastric
      cancers with positive STN expression.

PMID- 8260234
TI  - Sarcomatoid tumours of the breast in Denmark from 1977 to 1987. A
      clinicopathological and immunohistochemical study of 100 cases.
AB  - One hundred sarcomatoid breast tumours, which had been diagnosed and registered
      in Denmark from January 1977 to January 1987, were subclassified using a
      combination of conventional morphological evaluation and immunohistochemistry,
      and the diagnosis was in each case related to clinical follow-up of 5-14 years or
      until death of the patient. Conventional histological examination resulted in 36
      benign, 19 borderline and 18 malignant phyllodes tumours, 1 angiosarcoma and 26
      non-specified sarcomatous tumours, 6 with small carcinoma-like foci.
      Immunohistochemical staining revealed that 23 of the non-phylloid sarcomatous
      tumours showed a tumour cell reaction for epithelial markers, predominantly
      cytokeratin and, therefore, the tumours were interpreted as metaplastic
      carcinomas. Clinical follow-up showed for phyllodes tumours and for the three
      cytokeratin-negative sarcomatous tumours local recurrence rates of 21 and 33%,
      respectively, whereas metastases only occurred from the angiosarcoma and from one
      borderline phyllodes tumour with five recurrences (5%). In contrast, metaplastic
      carcinomas gave rise to distant metastases in 50% of cases but no local
      recurrences. Axillary lymph nodes had been examined in 28 cases, 13 from
      metaplastic carcinomas. Only two of these showed metastatic spread, both with a
      pattern similar to the primary tumour. The differences in survival between
      patients with metaplastic carcinoma and patients with a borderline/malignant
      phyllodes tumour or a cytokeratin-negative sarcomatous tumour has in this study
      proven to be highly significant (P < 0.0001), and we find it of importance to use
      immunohistochemistry in the subclassification of sarcomatous breast tumours for
      appropriate surgery, reliable prognostic outlook and optimal postoperative
      therapy.

PMID- 8260235
TI  - Adjuvant chemotherapy with a nitrosourea-based protocol in advanced malignant
      melanoma.
AB  - 173 patients with regional lymphatic metastases (n = 139) or distant disease (n =
      34) were prospectively randomised, following resection of all clinically
      detectable tumour, to observation (n = 88) or adjuvant chemotherapy (n = 85). The
      treatment group received 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) 80 mg/m2
      intravenously (i.v.) every 4 weeks, and actinomycin-D 10 micrograms/kg,
      vincristine 1.0 mg/m2 i.v. every 2 weeks for 6 months. The disease-free survival
      curves between the two groups were significantly different (P = 0.03). The
      estimated 5-year disease-free survival rate for the observation group was 9% and
      for the treatment group 29%. However, the overall survival curves were not
      significantly different for the two groups. Nitrosoureas may have a weak effect
      as adjuvant treatment in malignant melanoma.

PMID- 8260236
TI  - Folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without
      cyclophosphamide in metastatic breast cancer.
AB  - 60 patients with metastatic breast cancer were entered in a phase II study using
      folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without
      cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively
      bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36
      with anthracycline-based regimens). Overall response rate in visceral metastatic
      patients was 57.1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in
      previously and non-previously treated patients, respectively; duration of
      response was 9 and 13 months, respectively. 10 out 13 patients with exclusive
      bone metastases improved for a median time of 18 months. Median survival was 22
      months for the 60 patients; 18 and 31 months for previously and non-previously
      treated patients, respectively. Cyclophosphamide was scheduled only in the
      absence of nadir grade 4 neutropenia. However, this toxicity occurred in the
      first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients
      over 60 years, or with a performance status of 1-2, or who had received previous
      chemotherapy. Overall, cyclophosphamide was stopped due to nadir grade 4
      neutropenia in 17/24 patients for whom this drug was planned. When mitoxantrone,
      5-fluorouracil and folinic acid were used at the doses scheduled, the addition of
      cyclophosphamide appeared feasible in only about 25% of the patients.
      Furthermore, survival was identical for patients receiving or not receiving
      cyclophosphamide. Therefore, cyclophosphamide does not contribute substantially
      to this regimen. This study confirms the value of folinic acid, 5-fluorouracil
      and mitoxantrone in metastatic breast cancer.

PMID- 8260237
TI  - Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia.
      The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).
AB  - A total of 2192 children with acute lymphoblastic leukaemia who had reached
      cessation of therapy in complete remission were followed for a median time of 52
      months after treatment suspension. Of the 485 relapses observed, 62.3% occurred
      in the first year off therapy and 68.9% involved the bone marrow. Eight relapses
      were reported more than 5 years (62-143 months) after treatment withdrawal. Males
      fared worse than females consistently, experiencing 1.5 times more relapses (P <
      0.0001). Thirteen patients died in continuous complete remission, 5 because of
      non-neoplastic central nervous system complications. There were 11 second solid
      malignancies, 8 of them in the central nervous system; 9 subjects presented an
      haematopoietic malignancy after ALL. The projected event-free survival at 8 years
      is 73%. Twenty-two of the 171 young adults (age > 20 years) were married and 16
      have had 21 healthy children. Twenty-four per cent of patients experienced an
      unfavourable event. Relapses accounted for 93% of failures. Central nervous
      system late effects and second malignancies were the major causes of non
      leukaemic morbidity and mortality.

PMID- 8260238
TI  - Cell cycle modifications of breast cancers during neoadjuvant chemotherapy: a
      flow cytometry study on fine needle aspirates.
AB  - Breast cancer cells from 92 patients were obtained by repeated fine needle
      sampling and analysed by flow cytometry for cell cycle modifications during
      neoadjuvant chemotherapy. Modifications of the histograms were observed for 47 of
      the 71 informative cases (66%), the most frequent concerning S-phase (increase or
      decrease) and G2M accumulation. These modifications correlated well with the
      efficacy of cytotoxic chemotherapy (P < 0.0001). A significant relationship
      between clinical regression and pretreatment proliferative activity was also
      observed, with 31/35 (89%) responders in the high proliferation group (S-phase
      fraction > 5% or BrdU labelling index > 3.3%) compared to 20/36 (56%) in the low
      proliferation group (P < 0.002). For patients undergoing chemotherapy including
      doxorubicin, a high incidence of G2M accumulation was observed (33%), a
      modification which was rare (4.5%) for a regimen with no anthracycline, for which
      S-phase was the most frequently modified cell cycle compartment (64%). The
      measurement of the pretreatment tumour proliferative activity as well as the
      early kinetic modifications, as indicators of response, may prove interesting
      parameters for the future management of neoadjuvant chemotherapy.

PMID- 8260239
TI  - MICE: a new active combination for non-small cell lung cancer.
AB  - We have treated 38 patients with stage III/IV non-small cell lung cancer with the
      following regimen: mitomycin-C = 6 mg/m2, ifosfamide = 3 g/m2, cisplatin = 75
      mg/m2, vindesine = 3 mg/m2 (MICE), intravenously (i.v.) on day 1, every 3 weeks.
      Among 26 patients with stage IV disease, 15 obtained a partial remission (PR)
      (response rate = 57%, 95% confidence interval = 38-76), with a median time to
      disease progression and a median survival of 4.9 and 7.1 months, respectively. 6
      out 7 patients with stage IIIA disease were documented as PR and 5 of them
      underwent radical surgery with two pathologically confirmed complete remissions.
      Overall toxicity was substantial but manageable: 3 patients had grade III/IV
      leucopenia (although 5 patients had neutropenic fever) whereas 13 patients
      experienced grade II/II anaemia. In conclusion we believe that MICE regimen is an
      interesting combination and warrants further evaluations both for palliation and
      in a neoadjuvant setting.

PMID- 8260240
TI  - Circadian rhythm-modulated chemotherapy with high-dose 5-fluorouracil: a pilot
      study in patients with pancreatic adenocarcinoma.
AB  - From November 1986 to April 1989, 16 patients with advanced measurable pancreatic
      carcinoma were involved in a pilot phase I-II study. 5-Fluorouracil was given
      every 3 weeks by 5-day continuous chronomodulated venous infusion (CMVI) with
      peak 5-FU delivery at 4 a.m. Intrapatient dose escalation started at 1200
      mg/m2/day up to 1600 mg/m2/day in the absence of grade III (WHO) toxicity.
      Mucositis and diarrhoea were dose limiting in the 131 cycles given. Three partial
      responses (21%) and 5 stable diseases were seen in the 14 patients with
      measurable disease. Dose intensity after three or after six courses (1800
      mg/m2/week) was significantly correlated with time to progression (Pearson r =
      0.64; P < 0.004). These results, although modest, support a multicentre phase II
      trial with 5-FU CMVI.

PMID- 8260241
TI  - A toxic interaction between mitomycin C and tamoxifen causing the haemolytic
      uraemic syndrome.
AB  - A comparison of patients receiving combination chemotherapy with mitomycin C,
      mitozantrone and methotrexate (3M) with and without tamoxifen for treatment of
      primary breast cancer indicates an increased risk of anaemia (P < 0.0001) and
      thrombocytopenia (P < 0.001), but not leucopenia for patients receiving tamoxifen
      with their chemotherapy compared to those receiving the chemotherapy alone.
      Furthermore, 9 out of 94 patients receiving tamoxifen with 3M developed
      progressive anaemia, thrombocytopenia and abnormal renal function as early
      features of microangiopathic haemolytic anaemia, progressing on to various
      degrees of the haemolytic uraemic syndrome (HUS). This is only rarely seen with
      patients receiving mitomycin C alone at higher doses than used in the 3M
      combination and in the presence of active metastatic disease. This syndrome can
      be fatal and 1 of our 9 patients died. These observations indicate that there may
      be an interaction between tamoxifen and mitomycin C, causing an increased
      incidence of anaemia, thrombocytopenia and an increased risk of HUS. The
      combination of these two drugs should be avoided or carefully monitored.

PMID- 8260242
TI  - The effects of a 24-h psychological training program on attitudes, communication
      skills and occupational stress in oncology: a randomised study.
AB  - The usefulness of psychological training programs (P.T.P.) in health care
      settings devoted to cancer care is beginning to be recognised but their content,
      form and effectiveness need further investigation. Seventy-two oncology nurses
      were randomly assigned to a 24-h P.T.P. or to a waiting list period. Attitudes
      were assessed by a semantic differential questionnaire, occupational stress was
      assessed by the Nursing Stress Scale and communication skills were assessed by
      standardised videotaped role-playing exercises. These were used to compare
      trained (T.S.) and control subjects (C.S.). The results show a significant
      training effect on attitudes (P = 0.05), especially on those related to self
      concept (P = 0.004), and on the level of occupational stress related to
      inadequate preparation (P = 0.02). Limited changes were found regarding post
      training communication skills. T.S. were significantly more in control of the
      interview than C.S. (P = 0.02). The results indicate that 24-h P.T.P. assessed
      here are effective. The data also demonstrate the need to consolidate the skills
      acquired by regular post-training sessions.

PMID- 8260243
TI  - The prognostic value of nuclear roundness and neopterin in ovarian cancer.
AB  - The prognostic value of clinical factors, morphometric features and neopterin, a
      marker for macrophage activation, was investigated retrospectively in 68 ovarian
      carcinoma patients. Nuclear roundness was a good predictor of patient survival.
      About 50% of our patients showed neopterin concentrations above the cut-off level
      of 275 mumol/mol creatinine. Interestingly, those patients with elevated urinary
      neopterin concentration, and thus displaying a sign of activation of cell
      mediated immunity, had a shorter survival than those with normal concentration.
      Applying a multivariate Cox regression analysis, the only independent parameters
      predicting patient survival were FIGO stage, residual disease, nuclear roundness
      and neopterin.

PMID- 8260244
TI  - Increasing survival of patients with urinary bladder cancer. A nationwide study
      in Sweden 1960-1986.
AB  - Survival rates were analysed in 29,055 patients with urinary bladder cancer
      diagnosed in Sweden from 1960 to 1986 and followed up until 1987. The 2-, 5- and
      10-year relative survival rates were 79, 70 and 64% for men and 75, 68 and 63%
      for women, respectively. Patients with a history of bladder cancer for at least
      15 years ran a negligible risk of dying from their disease. Prognosis was
      consistently better in younger than in older patients; below 50 years of age the
      5-year relative survival rate was 90%, as compared with 60% in patients aged 70
      79 years. Patients diagnosed between 1960 and 1964 had a 60% 5-year relative
      survival, as compared to 71% in those diagnosed between 1980 and 1984.
      Multivariate analyses further confirmed that age but not sex is an important
      prognostic factor in bladder cancer and, further, that a substantial improvement
      in survival rates took place during the 1960-1986 period. Compared with 1960-1964
      the risk of dying of bladder cancer within 5 years in patients diagnosed between
      1980 and 1984 was 51% lower in men [relative risk (RR) = 0.49; 95% confidence
      interval (C.I.) 0.42-0.57] and 44% lower in women (RR = 0.56; 95% C.I. 0.45
      0.70).

PMID- 8260245
TI  - Anti-leukaemic action of RuCl2 (DMSO)4 isomers and prevention of brain
      involvement on P388 leukaemia and on P388/DDP subline.
AB  - Two ruthenium(II) complexes, characterised by the presence of dimethylsulphoxide
      ligands, were investigated in comparison to cisplatin on mouse P388 leukaemia and
      on a subline made resistant to cisplatin (P388/DDP). Both cis- and trans
      RuCl2(DMSO)4 significantly prolonged the survival time of leukaemic mice,
      independently of the tumour line used. Unlike cisplatin, the prolongation of life
      span of tumour-bearing hosts caused by ruthenium complexes was not supported by a
      parallel inhibition of the number of tumour cells in the treated hosts, as
      evidenced by tumour cell count in the peritoneal cavity and by vivo-vivo
      bioassays of blood samples and of whole brains. Thus, cis- and trans-RuCl2(DMSO)4
      appear capable of preventing leukaemic spread into the central nervous system
      also when the number of tumour cells in the peritoneal cavity and in the blood
      stream is as high as in untreated controls. When the drug-induced DNA damage was
      investigated by modifying double stranded DNA and identifying the lesions able to
      inhibit DNA synthesis in vitro, trans-RuCl2(DMSO)4 and, to a lesser extent, cis
      RuCl2(DMSO)4 formed blocking lesions at the same sites of cisplatin;
      nevertheless, the mechanism of antitumour activity of ruthenium complexes appears
      to be different from that of cisplatin for the absence of any relationship
      between cytotoxicity and prevention of leukaemic dissemination into the central
      nervous system. These data indicate that the activity of cis- and trans
      RuCl2(DMSO)4 on the P388 leukaemia is characterised by the lack of cross
      resistance with cisplatin and by the alteration of the metastasising behaviour of
      leukaemic cells which lose their natural capacity to invade the central nervous
      system.

PMID- 8260247
TI  - Radioimmunodetection of human small cell lung carcinoma xenografts in the nude
      rat using 111in-labelled monoclonal antibody MOC-31.
AB  - The applicability of mouse monoclonal antibody MOC-31 for in vivo
      radioimmunodetection of human small cell lung cancer (SCLC) was investigated in a
      nude rat xenograft model. MOC-31 is reactive with a 38 kD pancarcinoma membrane
      antigen. [111In]DTPA-MOC-31 showed good in vivo immunolocalisation to xenografted
      SCLC cells, whereas antigen-related uptake was low in normal rat tissues and in a
      control antigen-negative, human-derived tumour. Non-antigen-related uptake in the
      liver could be blocked by pretreatment with irrelevant antibody. It is concluded
      that MOC-31 can be used for radioimmunodetection of SCLC in vivo and may be
      suitable as a targeting device in patients.

PMID- 8260246
TI  - The effect of alpha and gamma interferon on cell growth and histocompatibility
      antigen expression by human renal carcinoma cells in vitro.
AB  - Tumour cells were separated from 19 renal carcinomas and cultured in vitro. The
      effect of interferon (IFN) alpha and gamma on cell proliferation was measured and
      compared to the effect of IFN on the expression of class I and class II major
      histocompatibility complex (MHC) antigens. When tested within the first 14 days
      of culture, IFN-alpha inhibited protein synthesis in 12 of 15 and IFN-gamma in
      four of nine tumours. Reduction in cell counts was in parallel. In six tumours
      the culture period was extended and in all six the effect of IFN-alpha was lost.
      Exposure to IFN-alpha induced or enhanced class I antigen expression in eight of
      19 tumours and class II expression in two of 19. The analogous figures for IFN
      gamma were five and three tumours. In four of five cases where a comparison could
      be made there was a correlation between the effects of IFN-alpha on cell
      proliferation and class I antigen expression. The efficacy of IFN in the
      treatment of renal carcinomas may thus, in part, result from inhibition of cell
      proliferation and enhancement of antigen expression.

PMID- 8260248
TI  - Evaluation of the time-schedule dependency for the cytotoxic activity of the new
      vinca alkaloid derivative, S 12363 (vinfosiltine).
AB  - S 12363 is a new vinca alkaloid derivative obtained by appending an optically
      active alpha-aminophosphonate at the C23 position of 04-deacetyl vinblastine. The
      present study concerns four different human tumour cell lines, which represent
      the spectrum of vinca alkaloid clinical activity. The influence of time exposure
      on S 12363 growth inhibition was studied in vitro. Cells were exposed to the drug
      during the following exposure times: 5, 15, 30 min and 1, 3, 6, 12, 24, 48, 72,
      144 h. The concentrations of S 12363 applied were between 1 x 10(-2) and 1 x
      10(3) nmol/l. The cytotoxic effects were assessed by using the methyltetrazolium
      (MTT) semi-automated test. Considering the IC50 values in terms of concentration
      (C) x time (T), I (C x T)50, it was shown that for an equal growth inhibitory
      effect (50% of cell death) the increased exposure times required higher
      cumulative drug exposures. More precisely, only very long exposure (greater than
      24 h) resulted in very high I (C x T)50. The drug exposure ratios which
      correspond to I (C x T)50 values for 144 h divided by the I (C x T)50 values for
      0.25 h ranged between 2.8 and 18.3. If T and C had symmetrical effects on the
      final growth inhibition, the I (C x T)50 ratios should have been equal to one.
      For all cell lines investigated there were similar dose-response curves following
      two types of S12363 exposure: a single day exposure or three successive daily
      exposures, the total C x T values being the same in both experimental situations.
      The basic pharmacological information provided by the present study may encourage
      further clinical trials of this potentially interesting new vinca alkaloid.

PMID- 8260249
TI  - Immunological paradox in testicular tumours: the presence of a large number of
      activated T-cells despite the complete absence of MHC antigens.
AB  - Tissue sections from 22 seminoma (Se) and 10 teratoma (Te) patients were
      investigated for correlation between the presence of tumour infiltrating T
      lymphocytes (TIL) and the expression of major histocompatibility complex (MHC)
      antigens using an immunoperoxidase staining technique. Complete absence of both
      class I and II antigens was observed in all Te and 20 out of 22 Se. The two
      positive Se showed only weak expression on 2% of tumour cells. Despite the
      absence of human leucocyte antigens (HLA) there were a large number of TIL
      scattered throughout the tissues in the case of Se with no predominance of CD4 or
      CD8 subpopulations in either group. T gamma positive cells were less than 5% of
      total CD3 positive cells in both Se and Te. The majority of the TIL were found to
      express activation markers, i.e. HLA class II antigens. Culture of tumour cell
      suspension with IL-2 produced passageable IL-2-dependent T cells from 10 out of
      15 tumours. Studies with testis cell lines showed the complete absence of class I
      antigens in 2 out of 5 cases and the inability of interferon gamma (IFN gamma) to
      induce expression. IFN gamma also failed to induce class II antigens in three out
      of five of these lines. The immunological paradox of the presence of a large
      number of activated T-cells in testicular tumours despite the complete absence of
      MHC antigens remains unexplained and needs further investigation. Possible
      hypotheses are reviewed.

PMID- 8260250
TI  - Intravesical mitoxantrone in superficial bladder tumours (Ta-T1).
AB  - 36 patients with histologically proven grade G1-G2, Ta-T1 transitional cell
      carcinoma of the bladder were introduced, after transurethral resection (TUR),
      into a study of intravesical chemoprophylaxis with mitoxantrone (20 mg diluted in
      50 ml). After a mean follow-up of 23 months, 16 (50%) patients showed a
      superficial recurrence with a mean recurrence rate of 0.56 per year. In 19
      patients with recurring tumours the mean recurrence rate decreased from 1.65 to
      0.58 per year. 9 patients (25.7%) suffered from a chemical cystitis that in 2
      cases (5.7%) required treatment interruption.

PMID- 8260251
TI  - Phase I study of tauromustine administered in a weekly schedule.
AB  - Tauromustine was administered orally in weekly doses with interindividual dose
      escalation to patients with disseminated malignant melanoma. The dose in the
      first cohort of 6 patients was 20 mg/m2/week. The dose escalation was 5
      mg/m2/week. The limit of tolerance was 55 mg/m2/week. 99 patients completed at
      least 8 weeks of treatment and eight dose levels were evaluated for toxicity.
      Reversible thrombocytopenia, and to a lesser degree leukopenia, were dose
      limiting. From a starting dose of 40 mg/m2/week, the long-term tolerated dose was
      35 mg/m2/week, thus achieving a considerable increase of dose intensity without a
      significant increase of toxicity by employing this weekly schedule of
      tauromustine.

PMID- 8260252
TI  - Melanoma-associated antigens.

PMID- 8260253
TI  - Cancer Research Campaign operation manual for control recommendations for
      products derived from recombinant DNA technology prepared for investigational
      administration to patients with cancer in phase I trials.

PMID- 8260254
TI  - Cisplatin and continuous infusion vindesine and 5-fluorouracil in non-small cell
      lung cancer (NSCLC) (ATTIT 002). ATTIT (Association pour le Traitment des Tumeurs
      Intra-Thoraciques)

PMID- 8260255
TI  - Ineffectiveness of relaxation on vomiting induced by cancer chemotherapy.

PMID- 8260256
TI  - Tauromustine (TCNU) combined with 5-fluorouracil and leucovorin in the treatment
      of advanced colon cancer.

PMID- 8260257
TI  - Combination IL-2 and cisplatinum: a promising treatment for bronchioloalveolar
      carcinoma?

PMID- 8260258
TI  - Kaposi's sarcoma in the Swiss Canton of Vaud, 1974-1990.

PMID- 8260259
TI  - Histological classification of ductal carcinoma in situ.

PMID- 8260260
TI  - Optimal delivery of dose in cancer chemotherapy with the support of
      haematopoietic growth factors.
AB  - The delivery of cancer chemotherapy is often non-optimal because of dose
      reductions and delays related to various toxic effects. These result in a
      decrease of the dose intensity as well as of the relative dose intensity of a
      given regimen compared to a reference protocol. In retrospective studies, such
      modifications have been shown to negatively influence the therapeutic results in
      many clinical situations. The ability of haematopoietic growth factors to reduce
      chemotherapy-related neutropenia and its associated infectious complications
      allows better dose-on-time delivery of the chemotherapeutic drugs. The potential
      therapeutic impact of this effect remains to be determined in prospective
      studies.

PMID- 8260261
TI  - The importance of dose: lymphomas as a model of chemosensitive malignancies.
AB  - Chemotherapy dose intensity is probably important to the success of treatment for
      some human malignancies. Recombinant human haemopoietic growth factors have
      recently become available to clinicians to ameliorate the myelosuppression that
      follows cytotoxic chemotherapy. Their use to increase the dose intensity of
      treatment, either by simply allowing the administration of the planned dose on
      schedule or by increasing the dose or dose rate above the conventional ones, is
      being actively investigated by several European and American groups. In several
      reported studies, neutropenia is no longer dose limiting when granulocyte colony
      stimulating factor is used to help to intensify cytotoxic chemotherapy, but
      thrombocytopenia or mucositis are. The use of circulating haemopoietic progenitor
      cells, released into the blood stream by growth factors and infused with or
      without autologous bone marrow, has been reported to consistently reduce the
      overall period and severity of thrombocytopenia following intensive chemotherapy
      in patients without pre-existing severe bone marrow damage. However, no clear
      improvements in survival have yet been documented with the use of these
      techniques. Difficulties in study design include a number of variables
      potentially involved (tumour model, patient population, adjuvant or advanced
      disease, dose of cytotoxics, intervals, end-points, etc.), and there is clearly a
      need for more studies and longer follow-up. Lymphomas, both non-Hodgkin and
      Hodgkin's disease, are the prototypes of chemosensitive malignancies curable by
      chemotherapy alone even in disseminated disease. Therefore, they would seem to be
      adequate models to test the dose intensity hypothesis in the clinic. However,
      there are important differences between these two types of disorder. The success
      of conventional therapies in these conditions suggests that further improvements
      in outcome and long-term survival by further increases in dose intensity with
      current drugs will require careful study designs, due attention to prognostic
      factors, and reasonable expectations.

PMID- 8260262
TI  - Chemoimmunotherapy of metastatic malignant melanoma. The Salpetriere Hospital
      (SOMPS) experience.
AB  - Optimistic results were obtained in the treatment of 39 patients with surgically
      incurable metastatic malignant melanoma using a regimen including 2 to 3 monthly
      induction cycles of cis-diamminedichloroplatinum (CDDP), recombinant interleukin
      2 (rIL-2) and interferon alpha-2a (IFN alpha-2a). 33 of 39 patients were
      pretreated with chemotherapy (dacarbazine and/or fotemustine:31, CDDP:6) and 17
      of 39 with IFN alpha-2a. Overall response rate was 54% with 13% achieving a
      complete response for up to 59+ weeks. Moderate to severe side-effects were
      reversible on rIL-2 cessation and toxicity was manageable in a routine inpatient
      setting. These results are especially encouraging as they were seen in previously
      treated patients, classically low responders, including 3 who were resistant to
      cisplatin or other platinum complexes. The question remains if this regimen
      bypasses traditional mechanisms of drug resistance.

PMID- 8260263
TI  - Haematopoietic growth factors and peripheral blood stem cells as supportive
      agents in dose intensification.
AB  - We have studied the requirements that have to be met to combine effective cancer
      chemotherapy with the mobilisation of peripheral blood stem cells (PBSC). We have
      shown that there is a differential induction of high numbers of PBSC following
      standard-dose chemotherapy (VIP) plus treatment with colony-stimulating factors.
      The combined sequential administration of interleukin 3 (IL-3) plus granulocyte
      macrophage colony-stimulating factor (GM-CSF) induced maximal numbers of PBSC,
      including colony-forming unit-granulocyte, erythrocyte, monocyte/macrophage,
      megakaryocyte (CFU-GEMM) and colony-forming unit-megakaryocyte (CFU-Meg),
      compared with the application of GM-CSF, granulocyte colony-stimulating factor (G
      CSF) or chemotherapy alone. The number of CD34+ cells was highly variable
      depending on the prior treatment given to the patients. Mobilised CD34+ cells-
      depending on the cytokines used for recruitment--had a varying cloning
      efficiency, and were heterogeneous as to their level of commitment. Retransfusion
      of G-CSF-primed progenitor cells to pilot patients following high-dose
      chemotherapy demonstrated that PBSC recruited by standard-dose chemotherapy plus
      G-CSF accelerated both neutrophil and platelet recovery.

PMID- 8260264
TI  - Interleukin-2 in combination with interferon-alpha and 5-fluorouracil for
      metastatic renal cell cancer.
AB  - Recent clinical trials for the biological therapy of solid tumours have used
      recombinant human cytokines in combination with conventional chemotherapy. In
      patients with progressive metastatic renal cell carcinoma, we established a three
      drug combination comprising interferon-alpha (IFN-alpha), interleukin-2 (IL-2)
      and 5-fluorouracil (5-FU), using a regimen which allows outpatient therapy.
      Treatment consisted of 8 weeks each of IFN-alpha [6-9 MU/m2 once to three times
      weekly subcutaneously (sc)] combined sequentially with IL-2 (5-20 MU/m2 thrice
      weekly sc for 4 weeks) and 5-FU [750 mg/m2 intravenously (i.v.) weekly for 4
      weeks]. Among the first 35 patients treated, there were 4 complete (11.4%) and 13
      partial responders (37.1%), with an overall objective response rate of 48.6% (95%
      confidence interval 32-66%). Regressions occurred in local relapse, in lung,
      lymph node, bone, pleural, renal and thyroid metastases. Median response duration
      was calculated at 7+ months. An additional 13 patients (37.1%) were stable
      throughout therapy and thereafter (median of 6+ months). Response rate of this
      three-drug combination regimen compared favourably with single agent IFN-alpha
      (objective response rate approximately 16%) and against the sc IFN-alpha/IL-2
      combination (objective response rate approximately 28%). Systemic toxicity was
      mild to moderate with no severe 5-FU-related mucositis and no dose-limiting
      adverse effects of sc IL-2. While the exact mechanisms of the potentially
      additive or synergistic effects of 5-FU and IFN-alpha/IL-2 remain to be
      established in more detail, it appears that the sequential use of IFN-alpha/IL-2
      and IFN-alpha/5-FU in metastatic renal carcinoma further enhances the therapeutic
      index of IFN-alpha/IL-2-based biological therapy. Based on the present data,
      combined biochemotherapy may be a promising new approach to the therapy of
      advanced renal cancer.

PMID- 8260265
TI  - Retinoic acid and interferon combination studies in human cancer.
AB  - Retinoic acid and interferon-alpha have limited single-agent activity in advanced
      cancer. Cell culture data indicate that in combination these agents have enhanced
      activity (modulating growth and differentiation) in a number of malignant cell
      types. Recent clinical work in advanced squamous cell carcinoma reports major
      activity with this regimen. This paper reviews the preclinical and clinical data
      testing retinoic acid in combination with interferons and presents recent work
      integrating these agents with radiotherapy in locally advanced cervical cancer.

PMID- 8260266
TI  - Plasma concentrations of brain natriuretic peptide: will this new test reduce the
      need for cardiac investigations?

PMID- 8260267
TI  - Which patients should have exercise testing after myocardial infarction treated
      by thrombolysis?

PMID- 8260268
TI  - Chronotropic incompetence: a proposal for definition and diagnosis.

PMID- 8260269
TI  - Pathological concepts in acute coronary thrombosis: relevance to treatment.

PMID- 8260270
TI  - Prognostic significance of N-terminal pro-atrial natriuretic factor (1-98) in
      acute myocardial infarction: comparison with atrial natriuretic factor (99-126)
      and clinical evaluation.
AB  - OBJECTIVE: To evaluate the prognostic significance of plasma N-terminal pro
      atrial natriuretic factor (1-98) concentrations measured in the subacute phase
      after acute myocardial infarction, and to compare the predictive value of
      measurement of N-terminal pro-atrial natriuretic factor (1-98) with the
      measurement of atrial natriuretic factor (99-126) and with clinical assessment of
      the degree of heart failure. DESIGN: Prospective observational. SETTING:
      Norwegian central hospital. PATIENTS: 139 patients (mean (SD) age 66.9 (11.1)
      years, 71.2% males) with acute myocardial infarction. Patients in cardiogenic
      shock or with severe heart failure (New York Heart Association class IV) were
      excluded. MAIN OUTCOME MEASURE: Cardiovascular death within 12 months. RESULTS:
      During the follow up period 15 patients died. In a univariate Cox proportional
      hazards model N-terminal pro-atrial natriuretic factor (1-98) was significantly
      related to mortality (p = 0.0003). In a multivariate model the prognostic value
      of N-terminal pro-atrial natriuretic factor (1-98) was better than that of atrial
      natriuretic factor (99-126) and clinical assessment of heart failure (N-terminal
      pro-atrial natriuretic factor (1-98), p = 0.0003; atrial natriuretic factor (99
      126), p = 0.4513; heart failure, p = 0.0719). The odds ratio estimate of patients
      in whom plasma concentrations of N-terminal pro-atrial natriuretic factor (1-98)
      were greater than 2000 pmol/l was 25 (95% confidence interval 2.8-225.0) compared
      with patients with plasma concentrations less than 1000 pmol/l. CONCLUSIONS:
      These results suggest that determination of plasma N-terminal pro-atrial
      natriuretic factor (1-98) in the subacute phase of myocardial infarction may
      provide clinically relevant prognostic information that is superior to that
      obtained from atrial natriuretic factor (99-126) measurements and clinical
      evaluation.

PMID- 8260271
TI  - Reassessment of treadmill stress testing for risk stratification in patients with
      acute myocardial infarction treated by thrombolysis.
AB  - OBJECTIVES: To evaluate the role of a treadmill stress test for identifying
      patients at risk of recurrent ischaemic events after acute myocardial infarction
      treated by thrombolysis. BACKGROUND: The natural history of myocardial infarction
      has changed with the introduction of thrombolytic treatment; there is a lower
      mortality but a higher incidence of recurrent thrombotic events (reinfarction,
      unstable angina). The treadmill stress continues to be recommended for risk
      stratification after acute myocardial infarction even though its value has never
      been formally reassessed in the thrombolytic era. METHODS: Prospective
      observational study in which 256 consecutive patients who presented with acute
      myocardial infarction treated by thrombolysis underwent an early treadmill stress
      test and were followed up for 10 (range 6-12) months. RESULTS: Recurrent
      ischaemic events occurred in 41 patients (unstable angina 15, reinfarction 21,
      death five) and a further 21 required revascularisation. Both ST depression at a
      low workload and low exercise tolerance (< 7 metabolic equivalents of the task
      (METS) were predictive of recurrent events, with respective hazard ratios of 1.93
      (95% confidence interval (95% CI) 1.17-3.20; p < 0.01)) and 1.67 (95% CI 1.0
      2.78; p < 0.05). These variables identified 50% and 70% of patients who
      subsequently sustained a recurrent ischaemic event, but the corresponding values
      for positive predictive accuracy were only 26% and 21%. Thus they are of limited
      value as a screening measure for identifying patients likely to benefit from
      invasive investigation and revascularisation. None of the other variables (ST
      elevation, haemodynamic responses, ventricular extrasystoles, angina) was
      significantly associated with recurrent ischaemic events. CONCLUSIONS: The
      treadmill stress test is of limited value for identifying patients at risk of
      recurrent ischaemic events after acute myocardial infarction treated by
      thrombolysis.

PMID- 8260272
TI  - Contribution of the 24 hour electrocardiogram to the prediction of sudden
      coronary death.
AB  - BACKGROUND: Sudden coronary death is a major public health issue. The
      identification of patients at high risk should therefore be as efficient as
      possible. This study compares simple and more elaborate risk stratification
      procedures. METHODS: Risk functions for the prediction of sudden death were
      determined in a population of 6693 consecutive patients who had 24 hour
      electrocardiography for various indications. The functions were based on the
      clinical and electrocardiographical data on 245 patients who died suddenly during
      2 year follow up and 467 patients randomly drawn from the total study population.
      RESULTS: The model based on history (age, sex, myocardial infarction, congestive
      heart failure, palpitation, syncope, use of diuretics, and use of nitrates), 12
      lead electrocardiography (major intraventricular conduction defect, T wave
      abnormality, and ST depression > or = 0.05 mV), and standard rhythm analysis of
      24 hour electrocardiography (ventricular tachycardia, frequent premature atrial
      complexes, sinus tachycardia (> 150 min-1), and atrial fibrillation) was almost
      as efficient in the prediction of sudden death as extended models that also
      contained information from exercise testing, echocardiography, ventriculography,
      and computer-aided re-analysis of 24 hour electrocardiography (QT and RR interval
      variability). CONCLUSIONS: These results indicate that additional information
      from advanced function tests does little to increase the efficiency of prediction
      of sudden coronary death over that of tests based on history, the standard 12
      lead electrocardiogram, and 24 hour electrocardiography.

PMID- 8260273
TI  - First myocardial infarction in patients under 60 years old: the role of exercise
      tests and symptoms in deciding whom to catheterise.
AB  - OBJECTIVE: To determine the role of exercise tests and assessment of angina in
      the detection of potentially threatening disease in young patients with infarcts.
      DESIGN: Elective readmission of patients at a mean (SD) of 60 (30) days after
      acute myocardial infarction for assessment of angina, treadmill exercise tests,
      and cardiac catheterisation. SETTING: Cardiology department of a teaching
      hospital. PATIENTS: 186 consecutive survivors, aged under 60 years and discharged
      from the coronary care unit after a first myocardial infarction. MAIN OUTCOME
      MEASURES: Coronary arteriography, presence of angina, result of exercise tests,
      and referral for revascularisation. RESULTS: 31% of patients had either two
      vessel disease (with proximal left anterior descending involvement), three vessel
      disease, or left main stem disease. 49% of all patients had angina. Of the 173
      patients who had an exercise test 34% had 1 mm and 24% had 2 mm of exercise
      induced ST depression. Thirty percent had no angina and a negative exercise test:
      after a mean (SD) follow up of 16 (4) months none of this symptom free sub-group
      had died, had experienced a further myocardial infarction, or had been referred
      for revascularisation. 79% of patients with either two vessel disease (with
      proximal left anterior descending involvement), three vessel disease, or left
      main stem disease had either angina or a 1 mm ST depression during the exercise
      test. CONCLUSION: Patients without cardiac pain after myocardial infarction and
      without ST changes during an exercise do not need arteriography.

PMID- 8260274
TI  - Holter ST monitoring early after acute myocardial infarction: mechanisms of
      ischaemia in patients treated by thrombolysis.
AB  - OBJECTIVE: To investigate the mechanisms of Holter ST shift in patients with
      acute myocardial infarction treated by thrombolysis. DESIGN: Prospective
      observational study. SETTING: A London district general hospital. SUBJECTS: The
      study group consisted of 94 patients with acute myocardial infarction treated by
      thrombolysis. INTERVENTIONS: All underwent early 48 hour Holter ST monitoring and
      elective coronary arteriography. MAIN OUTCOME MEASURES: Relation of Holter ST
      shift to multivessel coronary disease, coronary patency, collateralisation, and
      morphology of the infarct related lesion. RESULTS: There was a trend towards an
      increased prevalence of Holter ST shift in patients with patency of the infarct
      related artery and those with multivessel disease. This was only significant in
      patients with three vessel disease, a significantly higher proportion of whom had
      > 3 episodes of ST shift (41% v 14%; p = 0.02) or a total duration of ST shift >
      1 hour (35% v 13%; p = 0.04) than those with less extensive coronary disease.
      Holter ST shift occurred in a significantly higher proportion of patients with
      complex lesion morphology (Ambrose type 2 or 3) compared with those with lesions
      of Ambrose morphology type 1 or 2 (60% v 33%; p = 0.05). CONCLUSION: Holter ST
      shift detected early after thrombolysis is an ischaemic phenomenon with a complex
      pathophysiology. It reflects both remote ischaemia in patients with multivessel
      disease, and dynamic ischaemic processes related to complex lesion morphology in
      those with a patent infarct related artery.

PMID- 8260275
TI  - Myocardial ischaemia and angina in the early post-infarction period: a comparison
      with patients with stable coronary artery disease.
AB  - OBJECTIVE: To evaluate Holter and treadmill responses in patients with stable
      angina or recent myocardial infarction in order to compare the mechanisms of
      ischaemia and its symptomatic expression in these two groups. PATIENTS: 75
      patients with ischaemic ST segment depression on both a treadmill stress test and
      ambulatory Holter monitoring. Group A comprised 35 patients with stable angina,
      and group B comprised 40 patients in the early period after infarction. SETTING:
      The coronary care unit and cardiology department of a district general hospital.
      DESIGN: A prospective, between group, comparative study. RESULTS: Treadmill test
      showed demand driven ischaemia in both groups. Although ST depression occurred at
      comparable rate-pressure products and workloads, it was associated with angina in
      80% of group A compared with only 40% of group B (p < 0.005). During Holter
      monitoring, ST depression was associated with an attenuated increase in rate in
      group A and almost no increase in rate in group B (18.2% v 3.7%; p < 0.005),
      suggesting that reductions in myocardial oxygen delivery were contributing to the
      ischaemic episodes, particularly in group B. Ischaemic episodes were more
      commonly silent during Holter monitoring, particularly patients in group B, only
      two of whom experienced angina in association with ST depression. Spectral and
      non-spectral measures of heart rate variability were significantly reduced in
      group B compared with group A. Patients with silent exertional ischaemia in group
      A had significantly less heart rate variability than patients who experienced
      angina but this difference was not seen in group B. CONCLUSION: In stable angina,
      myocardial ischaemia is usually painful and demand driven, whereas in the early
      period after infarction silent, supply driven ischaemia predominates. The failure
      of myocardial ischaemia to provoke symptoms in some patients with stable angina
      may be related to autonomic dysfunction affecting the sensory supply to the
      heart. In the early period after infarction despite clear evidence of autonomic
      dysfunction, other mechanisms must also be important as there was no tendency for
      the reduction in heart rate variability to be exaggerated in the subgroup with
      silent exertional ischaemia.

PMID- 8260276
TI  - Importance of oxygen-haemoglobin binding to oxygen transport in congestive heart
      failure.
AB  - OBJECTIVE: To assess the importance of 2,3-diphosphoglycerate (2,3-DPG) and
      oxygen-haemoglobin binding to oxygen transport in patients with congestive heart
      failure. METHODS: In 30 patients with severe congestive heart failure, arterial,
      mixed venous, and coronary sinus venous blood concentrations of 2,3-DPG were
      measured and systemic output and coronary sinus blood flow were measured by a
      thermodilution technique. Oxygen-haemoglobin affinity was expressed as the oxygen
      tension in mm Hg at which blood is 50% saturated with oxygen (P50). RESULTS:
      Compared with normal values, 2,3-DPG was high in arterial blood (2.58 mumol/ml, p
      = 0.01; 20.8 mumol/g haemoglobin, p < 0.0001). Significant gradients between
      arterial, mixed venous, and coronary sinus blood 2,3-DPG concentrations were also
      found (mixed venous = 2.40 mumol/ml, p = 0.05 v arterial blood; coronary sinus
      venous blood = 2.23 mumol/ml, p < 0.04 v arterial blood). P50 was correspondingly
      high compared with the accepted normal value (mean 29.7 mm Hg, normal 26.6 mm Hg,
      p < 0.001). Systemic oxygen transport (351 ml O2/min/m2) varied directly with the
      forward cardiac index (r = 0.89, p < 0.0001). There was no relation between
      systemic oxygen transport and arterial oxygen content. Similarly, myocardial
      oxygen transport was found to vary directly with coronary sinus blood flow.
      Calculations of changes in cardiac index and coronary sinus blood flow at normal
      oxygen-haemoglobin binding indicate that a considerable increase in cardiac index
      and coronary blood flow would be required to maintain similar systemic and
      myocardial oxygen transport. CONCLUSIONS: In patients with severe heart failure
      increased 2,3-DPG and reduced oxygen-haemoglobin binding may be compensatory
      mechanisms that maintain adequate systemic and delivery of oxygen to myocardial
      tissue.

PMID- 8260277
TI  - Comparison of acoustic quantification and Doppler echocardiography in assessment
      of left ventricular diastolic variables.
AB  - OBJECTIVE: To assess the haemodynamic correlations of the waveforms of left
      ventricular area change obtained by automated boundary detection with newly
      developed acoustic quantification technology. DESIGN: The timing of events in the
      cardiac cycle was identified on the wave-form automated boundary detection and
      was correlated with the corresponding timing derived from pulsed wave Doppler
      flow velocity traces of the mitral valve and left ventricular outflow tract. The
      amounts of area change during the rapid filling phase and during atrial
      contraction were correlated with the time-velocity integrals of early and late
      diastolic ventricular filling obtained from Doppler tracings of the mitral
      inflow. SETTING: A university medical school echocardiography laboratory.
      SUBJECTS: 16 healthy volunteers and 19 patients referred for echocardiographic
      studies. RESULTS: A significant correlation was found between the methods for
      measurement of the time from the R wave to mitral valve opening (r = 0.72, p <
      0.01), isovolumic relaxation time (r = 0.62, p < 0.01), and ejection time (r =
      0.54, p < 0.01). The change of total area that occurred during rapid filling and
      atrial filling phases measured from the acoustic waveform correlated with the
      time-velocity integrals of the early and late diastolic mitral valve inflow
      velocity derived from Doppler echocardiography (r = 0.60 and r = 0.80,
      respectively). CONCLUSION: The waveform of left ventricular area obtained by the
      automated boundary detection technique identifies the phases of the cardiac cycle
      and correlates with Doppler values of left ventricular diastolic function.
      Therefore, this new method of automated boundary detection has potential uses in
      the assessment of left ventricular diastolic function.

PMID- 8260278
TI  - Determinants of the Doppler flow velocity profile through the mitral valve of the
      human fetus.
AB  - OBJECTIVE: A normal fetal flow velocity profile through the atrioventricular
      valves early in gestation is characterised by a higher late peak (A) than early
      peak (E) velocity waveform, whereas the E/A ratio is known to increase throughout
      pregnancy. This study aims firstly to identify which of the two variables, E or
      A, is the contributory factor to the increased E/A ratio and secondly to assess
      the relative influence of gestational age, heart rate, and stroke volume on the
      flow velocity profile through the fetal mitral valve. DESIGN: Eighty normal
      fetuses from 18 to 38 weeks of gestation were examined by Doppler
      echocardiography. The variables measured were E and A waves, the early and late
      flow velocity integrals (EI and AI), and the total filling velocity integral
      (TI). The ratios E/A and EI/AI were also calculated. Transvalvar flow was
      obtained by multiplying TI by mitral area. Associations between Doppler variables
      and gestational age, heart rate, and stroke volume were assessed by
      multifactorial Anova and simple or multiple stepwise regression analyses.
      RESULTS: The results showed that the heart rates found did not affect flow
      velocity variables. There were only weak correlations between both A and AI
      values and gestational age (negative) and volume load (positive). With the
      advance in gestation, a significant increase in the early filling E wave was
      found. The E wave was also positively correlated with stroke volume. CONCLUSION:
      Contrary to the accepted concept that changes in fetal E/A ratio are related to
      an improvement in ventricular compliance, this study shows that only the E wave
      changes. Although these results cannot establish whether changes in the
      ventricular relaxation process or volume load are responsible for the progressive
      increase of the E wave, indirect evidence suggests that ventricular relaxation is
      in fact the most important contributory factor.

PMID- 8260280
TI  - Cardiac arrest in a young woman with the long QT syndrome and concomitant
      astemizole ingestion.
AB  - Ventricular fibrillation developed in a 19 year old woman taking the
      antihistamine astemizole. She was successfully resuscitated. QTc prolongation was
      found and persisted despite withdrawal of the drug. Aggravation of congenital
      long QTc syndrome by astemizole is postulated. More caution should be exercised
      with the use of this drug.

PMID- 8260279
TI  - Profile of paediatric patients with pulmonary hypertension judged by
      responsiveness to vasodilators.
AB  - OBJECTIVE: To describe the demographic and haemodynamic variables of children
      presenting with primary pulmonary hypertension or pulmonary hypertension
      appearing or persisting after surgical correction of congenital heart defects and
      to assess the acute effect of vasodilator drugs on their pulmonary vascular bed.
      DESIGN: Retrospective review. SETTING: Paediatric cardiology department and
      intensive care unit of a large tertiary centre. PATIENTS: Fourteen consecutive
      patients presenting with primary pulmonary hypertension (group 1) or pulmonary
      hypertension persisting or appearing late after complete surgical repair (group
      2). INTERVENTION: Baseline haemodynamic measurements were taken in room air at
      rest and repeated in 100% oxygen. With constant monitoring of heart rate and
      pulmonary and systemic arterial pressures, patients were given serial
      intravenous, sublingual, or oral incremental doses of vasodilators (mean 4.1
      trials per patient). The maximum effect of the drug was charted. MAIN OUTCOME
      MEASURES: A positive response to acute vasodilator tests was defined as a
      decrease in mean pulmonary or mean systemic arterial pressure > 15% with the mean
      pulmonary artery pressure not reaching the systemic level and either no change or
      an increase in mean systemic arterial pressure. Haemodynamic variables between
      groups (1 v 2, responders v non-responders, patients experiencing or not
      experiencing adverse effects to vasodilators) were compared by a two tailed
      unpaired Student's t test, and their survival curves were compared by the log
      rank statistic. RESULTS: Groups are small and definitive conclusions are
      difficult to draw, but the baseline haemodynamic assessments were not
      significantly different between group 1 and 2 or between responders and non
      responders to vasodilators. Patients experiencing adverse effects had a higher
      pulmonary vascular resistance (p = 0.04) and wedge pressure (p = 0.02) than those
      without adverse effects. Of the vasodilators used, tolazoline, hydralazine,
      salbutamol, phentolamine, and phenoxybenzamine were ineffective. A positive
      response was seen in five of 13 patients given oxygen, in one of eight given
      prostacyclin, four of 12 given nifedipine, four of eight given diltiazem, one of
      six given captopril, and two of seven given glyceryl trinitrate. Estimates of
      survival of the population with primary pulmonary hypertension were 37% at one
      year and 12% at 2.5 years. Survival was significantly shorter in the non
      responders than in the responders (p = 0.005). CONCLUSION: Children with primary
      pulmonary hypertension present to the cardiologist at a young age (five of eight
      were younger than 7 years) but with advanced pulmonary vascular disease and have
      a poor prognosis. 64% of group 1 and group 2 patients had a positive response to
      acute treatment with at least one vasodilator. Calcium channel blockers were the
      most effective agents. There was a positive response to drugs despite a negative
      response to acute treatment with oxygen. The survival of non-responders was
      shorter than that of the responders.

PMID- 8260281
TI  - Two unusual complications after surgical interruption of an accessory pathway.
AB  - In a patient with the Wolff-Parkinson-White syndrome, Ebstein's anomaly of the
      tricuspid valve, a right atrial Chiari net and a patent foramen ovale two unusual
      complications developed after surgical epicardial dissection combined with
      cryoablation of the anomalous pathway. The first complication was that ablation
      of the right atrial wall led to changes in interatrial pressure gradients and the
      development of a right to left shunt necessitating surgical closure of the atrial
      septal defect. The second complication was the development of a thrombotic mass
      in the Chiari net simulating on intracavity tumour, which also had to be removed
      surgically.

PMID- 8260282
TI  - Primary hyperparathyroidism presenting as torsades de pointes.

PMID- 8260283
TI  - Recanalisation of an occluded modified Blalock-Taussig shunt by balloon
      dilatation.
AB  - A four year old boy with pulmonary atresia and ventricular septal defect had an
      acute cyanotic episode three years after undergoing a right-sided, 6 mm diameter,
      modified Blalock-Taussig shunt. On admission no continuous murmur could be heard
      from the shunt and the typical high velocity, continuous flow profile of the
      shunt could not be identified by Doppler echocardiography. At catheterisation a
      right subclavian artery angiogram confirmed shunt occlusion. From the subclavian
      artery, an 0.035 inch wire was used to enter the occluded shunt and then the
      pulmonary artery. Balloon angioplasty of the entire length of the shunt was
      performed with 6 mm diameter balloon. After angioplasty the arterial oxygen
      saturation increased from 63% to 83%. The patient was treated with intravenous
      heparin followed by warfarin. Repeat catheterisation and angiography eight days
      later confirmed wide patency of the shunt.

PMID- 8260284
TI  - Initial experience with balloon dilatation of supravalvar aortic stenosis.
AB  - Primary balloon dilatation of supravalvar aortic stenosis was attempted in three
      patients: a 20 year old woman, a seven month old boy, and a 12 year old girl.
      Balloon catheters (Mansfield) with diameters of 25 mm, 8 mm, and 15 mm were used
      in the three patients respectively. The systolic pressure gradient across the
      aortic narrowing decreased considerably and the diameter of the constricted area
      increased significantly. Balloon dilatation was feasible and provided good
      immediate results and sustained relief of supravalvar aortic stenosis in these
      three patients. However, a larger study is needed to establish the place of this
      procedure in treatment.

PMID- 8260285
TI  - Use of a remotely controlled mechanical pump for coronary arteriography: a study
      of radiation exposure and quality implications.
AB  - BACKGROUND: Exposure to radiation is a hazard of invasive cardiology. To minimise
      the risk it is essential to keep the doses received as low as possible. AIM: To
      assess the effect on cardiologist radiation exposure and the quality of coronary
      artery opacification of the use of a remotely controlled mechanical pump for
      coronary arteriography. A secondary aim was to assess any disadvantages and
      safety. METHODS: 319 patients were randomised to have coronary arteriography
      carried out with contrast injected either by hand or by a remotely controlled
      mechanical pump. Six cardiologists participated: two catheter laboratories were
      used and both brachial and femoral approaches were included. The exposure of the
      cardiologists to radiation was assessed by film badge dosimetry. The badges were
      worn on the hat. The total time for the procedure, screening time, the dose-area
      product meter reading, and any complications were recorded for each examination.
      The quality of arterial opacification was reported on a scale of 0-5. RESULTS:
      The mean radiation dose per procedure was 0.011 mSv for hand injection of
      contrast and 0.005 mSv for mechanical injection (p < 0.01). There were no
      differences in procedure times or screening times. There were no complications
      attributable to mechanical injection. Arterial opacification was not
      significantly different in the two groups (4.01 v 4.03 for the left coronary
      artery, 4.68 v 4.78 for the right coronary artery). The right coronary artery was
      consistently better opacified than the left by both techniques (4.59 v 3.89, p <
      0.001). CONCLUSIONS: Use of a remotely controlled mechanical pump for coronary
      arteriography reduced cardiologist radiation exposure by half. It was not
      associated with any inconvenience, expense, or complications and produced
      arterial opacification at least as good as injection by hand.

PMID- 8260286
TI  - Emergency percutaneous transluminal coronary angioplasty (PTCA) for intractable
      ventricular arrhythmias associated with acute anterior myocardial infarction.

PMID- 8260287
TI  - Is there such a thing as normal sinus rate?

PMID- 8260288
TI  - Exercise testing when there is not a doctor present: recommendations of the
      Medical Practice Committee and Council of the British Cardiac Society.

PMID- 8260289
TI  - Regional analgesia and myocardial ischaemia.

PMID- 8260290
TI  - Conscious levels during anaesthesia.

PMID- 8260291
TI  - Myocardial ischaemia and spinal analgesia in patients with angina pectoris.
AB  - We have studied prospectively myocardial ischaemic events by Holter monitoring of
      ST-segment depression in patients with angina pectoris given spinal analgesia for
      minor surgery compared with a reference day of normal daily activities.
      Monitoring was undertaken continuously for 24 h on both days, starting just
      before anaesthesia on the day of surgery. On the reference day, seven of 14
      patients had 27 ischaemic events with mean max ST-depression of 0.15 mV and total
      duration of 143 min, compared with 10 of 14 patients with 70 ischaemic events
      with mean max ST-depression of 0.22 mV and total duration of 1078 min (P < 0.01
      for all). On the day of surgery, the first ischaemic event occurred a mean 338
      min (range 75-480 min) after spinal analgesia, and the duration of all first
      events was 480 min. On this day, the first ischaemic event was associated with
      increased heart rate (103 beat min-1 (range 66-131 beat min-1) compared with 92
      (60-122) beat min-1 during all events (P = 0.011)). In patients with angina
      pectoris, myocardial ischaemia did not occur immediately after the onset of
      spinal analgesia, but several hours later, corresponding to the cessation of
      block. This could be explained by increased cardiac pre- and afterload, probably
      further aggravated by the volume load.

PMID- 8260292
TI  - Effect of intraoperative inspired gas mixtures on postoperative nocturnal oxygen
      saturation.
AB  - Continuous postoperative nocturnal pulse oximetry was performed in 20 patients
      undergoing elective cholecystectomy to examine if the composition of anaesthetic
      gas mixtures affects postoperative gas exchange. The patients were allocated
      randomly to receive either nitrogen or nitrous oxide during anaesthesia, and
      oximetry was performed on the night before operation and the first and third
      nights after operation. Considerable oxygen desaturation was seen in both groups.
      During the first night after operation the proportion of the night during which
      oxygen saturation was less than 85% was greater in the nitrogen group than in the
      nitrous oxide group, but there was no significant difference between the mean
      overnight saturation values of the two groups.

PMID- 8260293
TI  - Causes of oxyhaemoglobin saturation instability in the postoperative period.
AB  - Healthy, young patients tend to have stable patterns of oxygen saturation (SaO2)
      in the perioperative period, but unstable patterns of oxygen saturation data in
      the postoperative period have been described which are associated with wide
      fluctuations in the value of SaO2 over short periods of time and with a
      propensity for severe desaturation. This investigation was designed to study the
      cause of these unstable, hypoxaemic patterns. SpO2 was measured by pulse oximetry
      in an "at risk" patient group (n = 20) before and after operation and displayed
      as sequential distribution diagrams and centile plots. In 16 of these patients
      SpO2 was determined also at different values of PlO2 (21-50 kPa) before and after
      operation. Instability of SpO2, assessed over periods of 1 h, was common (n = 18)
      after operation; it was caused by both acute desaturations and a fluctuating
      baseline SpO2. The PlO2 vs SpO2 relationship was displaced after operation, with
      both lateral (rightwards) and downwards displacement. The result was to bring the
      PlO2 to or near to the steep part of the curve. In patients who displayed an
      unstable pattern of SpO2 over a short period of time (< 5 min), this was
      abolished by increasing PlO2. We postulate that the displacement of the PlO2 vs
      SpO2 curve increases the propensity to desaturation in those patients with
      impaired control by placing the steep part of the curve near to a PlO2 value of
      21 kPa.

PMID- 8260294
TI  - Analysis of factors which affect the relationship between inspired oxygen partial
      pressure and arterial oxygen saturation.
AB  - The adoption of pulse oximetry in anaesthesia and intensive care has resulted in
      oxyhaemoglobin saturation (SaO2) becoming an important and widely used clinical
      descriptor of gas exchange, although its full potential has not been realized. We
      have explored the effect of impaired gas exchange on the relationship between
      PIO2 and SaO2. A curve of oxygen content vs PIO2 for an ideal lung was
      constructed using the oxygen dissociation curve and allowing for the effect of
      dissolved oxygen in plasma. A plot of PIO2 vs SaO2 was derived from this content
      curve. The effect of impaired gas exchange (shunt and V/Q effects) on this
      relationship was then modelled using for shunt the equation Qs/Qt = (Cc' O2
      CaO2)/(Cc' O2-CvO2) and for V/Q, a graphical method using the equation V/Q =
      k(Cc' O2-CvO2)/ (PIO2-PAO2) and the oxygen content curve to model the effect of a
      spread of V/Q ratios. A total of nine compartments were used to model the scatter
      of V/Q, and the size of these compartments were determined by their relative
      blood supply. Plots of PIO2 vs SaO2 were derived for different values of shunt
      and V/Q. The PIO2 vs SaO2 curve reflected the shape of the oxygen dissociation
      curve but lay to the right by PIO2-PAO2. Shunt caused a depression of the plateau
      of this curve with relatively little lateral movement, whereas a low mean V/Q
      ratio caused a marked rightwards lateral displacement. Increased IogSD Q caused a
      flattening of the relationship. The combined effect of shunt and a spread of V/Q
      ratios caused both lateral and vertical displacements. Thus a series of simple
      measurements of PIO2 and SaO2 gave information about both shunt and V/Q
      abnormality.

PMID- 8260295
TI  - Study of the anatomy of the extradural region using magnetic resonance imaging.
AB  - We have studied magnetic resonance images of the lumbar spine of 39 subjects to
      examine the anatomy of the lumbar extradural region. The segmental nature of the
      posterior extradural region at each lumbar level may explain reports of easier
      cranial passage of extradural catheters introduced by the paramedian approach.
      This approach may thus provide a more reliable route for rapid introduction of an
      extradural catheter during the needle-through-needle, combined spinal-extradural
      technique.

PMID- 8260296
TI  - Single space combined spinal-extradural technique for analgesia in labour.
AB  - We have used the single space combined spinal-extradural technique for mothers
      requesting analgesia in labour. Intrathecal plain bupivacaine 5 mg produced a
      median time to analgesia of 3 min. There was inadequate abdominal analgesia after
      10 min in 16% of recipients, although all had good perineal analgesia. The median
      height of block was T8 (range T4-L2) and mean duration of analgesia 72 (SD 21)
      min. Hypotension occurred in two of 30 mothers, but responded to fluids and
      ephedrine. There were no post-spinal headaches. This technique is suitable for
      those parturients requesting analgesia in active labour who may not have time to
      achieve extradural analgesia before delivery. The extradural catheter is used to
      improve analgesia if the subarachnoid block is inadequate, or if labour continues
      beyond the duration of the subarachnoid block.

PMID- 8260297
TI  - Effects of giving water 20-450 ml with oral diazepam premedication 1-2 h before
      operation.
AB  - We have studied the volume of water which should accompany diazepam 10 mg oral
      premedication given 1-2 h before induction of anaesthesia in 75 patients
      undergoing elective gynaecological laparoscopy. Twenty-five patients were given
      20 ml (group A), 25 patients 150 ml (group B), and 25 patients 300-450 ml of
      water (group C). There were no differences between the groups in gastric fluid
      volume and acidity. All groups reported a reduction in thirst and dryness of the
      mouth after water intake, while only group B reported significant anxiolysis.
      Eight patients in group C experienced augmented diuresis, compared with no
      patients in groups A and B. We conclude that 150 ml is the ideal amount of water
      given with oral premedication 1-2 h before anaesthesia.

PMID- 8260298
TI  - Pharmacokinetics and effects of i.m. alfentanil as premedication for day-case
      ophthalmic surgery in elderly patients.
AB  - We have studied the pharmacokinetics and effects of i.m. alfentanil as
      premedication for peribulbar block in 90 patients undergoing elective day-case
      cataract surgery. We compared alfentanil 12.5 micrograms kg-1 injected into the
      deltoid (n = 30) or gluteal muscle (n = 30) 15 min before the peribulbar block,
      and placebo (n = 30). The alfentanil concentrations were significantly greater in
      the deltoid group during the study and the mean peak concentration occurred more
      rapidly in this group. Only alfentanil injected into the deltoid muscle reduced
      pain (assessed with a visual analogue scale (VAS)) associated with the peribulbar
      block. A mild sedative effect (VAS) was found in both alfentanil groups. We
      conclude that i.m. alfentanil appears to be a suitable premedicant for short,
      painful procedures because it has a short duration of action and is not
      associated with any clinically significant side effects.

PMID- 8260299
TI  - Skin conductance responses to auditory stimuli and anticipatory responses before
      venepuncture in patients premedicated with diazepam or morphine.
AB  - We have measured the skin conductance response to innocuous auditory stimuli and
      the anticipatory response before venepuncture in 45 patients receiving diazepam,
      morphine or no premedication before general anaesthesia. Subjective ratings of
      anxiety and sedation were measured using visual analogue scales. Skin conductance
      was less in subjects receiving diazepam than in the other groups, and the pattern
      of change of skin conductance in this group indicated superior adaptation to the
      environment during presentation of the innocuous stimuli compared with the other
      groups. After warning of venepuncture there was a large increase in skin
      conductance in all groups. There was a significant relationship between anxiety
      and skin conductance in unpremedicated patients and those receiving diazepam.

PMID- 8260300
TI  - Nausea and vomiting after gynaecological surgery: a meta-analysis of factors
      affecting their incidence.
AB  - A total of 1442 patients who had major gynaecological surgery were recruited into
      three multicentre studies using a standard general anaesthetic technique in order
      to assess the efficacy of various doses of orally administered ondansetron in the
      prevention of postoperative nausea and vomiting. A total of 1257 patients were
      included in this analysis: 420 received oral formulations of placebo and 212, 296
      and 329 received ondansetron 1, 8 and 16 mg, respectively. The following factors
      were measured in these studies and were considered to have a possible influence
      on the proportion of patients experiencing postoperative nausea and vomiting: age
      of patient; volatile anaesthetic; intraoperative dose of fentanyl; postoperative
      dose of morphine; country; anaesthesia duration; neuromuscular blocker;
      neuromuscular block antagonist; premedicant; recovery time; type of surgery;
      antiemetic treatment; body weight. Using a process of elimination based on
      logistic regression techniques, the factors found to be the most important
      influences on the frequencies of nausea and vomiting were antiemetic treatment,
      type of surgery, neuromuscular blocker, country, volatile anaesthetic and age. A
      statistically significant interaction between type of surgery and age was
      observed. Adjusted probabilities of nausea and vomiting were obtained from the
      model, including all the above factors, together with the type of surgery by age
      interaction. Ondansetron 8 mg showed the smallest adjusted probability of nausea
      (0.54) and vomiting (0.34) and placebo the greatest (nausea 0.75, vomiting 0.61).
      A similar pattern of adjusted probabilities over neuromuscular blocking agents
      was seen for nausea and vomiting, with the greatest occurring in patients
      receiving pancuronium (nausea 0.74, vomiting 0.57) and the least in patients
      receiving alcuronium (nausea 0.59, vomiting 0.38).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8260301
TI  - Power spectral analysis of heart rate variability after spinal anaesthesia.
AB  - Power spectral analysis of heart rate (HR) variability is a useful tool with
      which to assess cardiac autonomic activity. The low frequency bands have been
      considered as both sympathetically and parasympathetically mediated components,
      while the high frequency bands have been assumed to be the parasympathetically
      mediated respiratory components. It has been anticipated that spinal anaesthesia
      to the thoracic level may modulate cardiac autonomic activity to reduce HR and
      arterial pressure by blocking cardiac sympathetic activity. In order to quantify
      the alterations in cardiac autonomic activity, we have analysed the power spectra
      of HR variability for 30 min after subarachnoid administration of hyperbaric
      amethocaine. Using 256-s R-R interval data obtained from continuously recorded
      ECG, low frequency (Lo: 0.04-0.15 Hz) and high frequency (Hi: 0.15-0.40 Hz) band
      widths were integrated and their serial alterations were computed by shifting
      subjected R-R intervals at 60-s intervals. After the subarachnoid injection,
      arterial pressure, HR and Lo decreased and Hi and the Hi:Lo ratio increased.
      These changes were observed within 15-20 min. Ventilatory frequency did not
      change throughout the study. These findings suggest that the decrease in HR and
      arterial pressure after subarachnoid administration of hyperbaric amethocaine
      reflect decreased sympathetic activity and increased parasympathetic activity in
      the cardiac autonomic nervous system.

PMID- 8260302
TI  - Lack of a ceiling effect for intrathecal buprenorphine on C fibre mediated
      somatosympathetic reflexes.
AB  - We observed that buprenorphine 20 micrograms kg-1 i.v. in dogs caused an initial
      significant reduction in both A delta and C fibre mediated somatosympathetic
      reflexes evoked by tibial and radial nerve stimulation, to approximately 75% and
      70% of control values. Larger doses (up to 100 micrograms kg-1 i.v.) had
      progressively less effect and the mean responses were depressed to only
      approximately 65% and 55% of control, indicating a ceiling effect. Buprenorphine
      450 micrograms intrathecally (i.t.) completely abolished tibial C fibre reflexes,
      but 20% of A delta responses could not be eliminated with doses up to 1050
      micrograms i.t. Fentanyl 100 micrograms kg-1 i.v. or 150 micrograms i.t. after
      buprenorphine i.v. or i.t., respectively, had little additional effect. This
      study confirms the limited ceiling effect of buprenorphine on nociceptive
      reflexes when administered systemically, and provides evidence that when
      administered i.t. in sufficient doses it abolishes the C responses (lack of
      ceiling effect for C responses), but the A delta responses show a plateau or
      ceiling effect.

PMID- 8260303
TI  - Lemakalim, a potassium channel agonist, reverses electrophysiological impairments
      induced by a large dose of bupivacaine in anaesthetized dogs.
AB  - We have examined the ability of lemakalim to correct bupivacaine-induced cardiac
      electrophysiological impairment in an experimental electrophysiological model in
      closed-chest dogs. Two groups (n = 6) of pentobarbitone-anaesthetized dogs were
      given atropine 0.2 mg kg-1 i.v., and bupivacine 4 mg kg-1 i.v. over 10 s. Group 2
      received also lemakalim 0.03 mg kg-1 i.v. Bupivacaine induced bradycardia,
      prolonged PR and His-ventricle (HV) intervals, QRS duration, QTc and JTc
      intervals, decreased left ventricular (LV) dP/dt max and increased LV end
      diastolic pressure. Lemakalim reversed bupivacaine-induced PR, HV, QRS, QTc and
      JTc prolongation, and did not worsen bupivacaine-induced bradycardia and
      haemodynamic depression. We conclude that lemakalim can antagonize the main
      deleterious electrophysiological effects induced by a large dose of bupivacaine
      in anaesthetized dogs.

PMID- 8260304
TI  - Fentanyl inhibits the uptake of [3H]noradrenaline in cultured neuronal cells.
AB  - We have examined how fentanyl modulates [3H]noradrenaline uptake in two cultured
      neuronal cell preparations, the human neuroblastoma SH-SY5Y and the rat
      phaeochromocytoma PC12. Fentanyl produced a significant, dose-dependent
      inhibition of [3H]noradrenaline uptake at concentrations in excess of 0.1 mumol
      litre-1 (P < 0.05) and 0.3 mumol litre-1 (P < 0.05) for PC12 and SH-SY5Y cells,
      respectively. However, these values exceed the serum concentration of fentanyl
      required to produce analgesia. At the maximum concentration examined (100 mumol
      litre-1), fentanyl produced 85-95% inhibition of uptake. This effect was not
      antagonized by naloxone, implying a nonopioid mechanism of action. Imipramine 1
      mumol litre-1 reduced [3H]noradrenaline uptake by 65-70% but morphine, in
      contrast to fentanyl, had no effect (P > 0.1).

PMID- 8260305
TI  - Mechanisms of the relaxant action of ketamine on isolated porcine trachealis
      muscle.
AB  - Ketamine is a potent bronchodilator, but its mode of action is unclear. We have
      studied the effect of ketamine on the peripheral vagus nerve motor pathway of
      isolated porcine trachealis muscle. Postsynaptic nicotinic cholinergic receptors
      of the intramural ganglia were stimulated selectively with 1,1-dimethyl-4-phenyl
      piperazinium iodide, post-ganglionic nerve fibres with electrical field
      stimulation (in the presence of hexamethonium) and muscarinic cholinergic
      receptors with acetylcholine (in the presence of tetrodotoxin). Ketamine 10(-4)
      mol litre-1 significantly shifted the concentration-response curves of
      acetylcholine (P < 0.02) and electrical field stimulation (P < 0.001) to the
      right and abolished the response to 1,1-dimethyl-4-phenyl-piperazinium iodide (P
      < 0.02). Ketamine also caused a concentration-dependent relaxation of muscle
      strips precontracted with acetylcholine. This was unaffected by propranolol.
      Ketamine relaxed muscle strips precontracted with potassium chloride, in the
      absence and presence of atropine. We conclude that ketamine interacts with the
      peripheral vagus nerve by decreasing the excitability of the postsynaptic
      nicotinic receptors of the intramural ganglia, and by affecting the muscarinic
      receptor, smooth muscle, or both. Beta-2 adrenoceptors are not involved in the
      mechanism of relaxation.

PMID- 8260306
TI  - Sevoflurane does not increase intracranial pressure in hyperventilated dogs.
AB  - We have measured the effects of 0.5, 1.0 and 1.5 MAC (minimum alveolar
      concentration) end-tidal concentrations of sevoflurane on intracranial pressure
      (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), central
      venous pressure and heart rate in hypocapnic dogs (PaCO2 3.2-3.7 kPa) and
      compared the data with those produced by equi-MAC concentrations of enflurane and
      halothane. Enflurane and halothane caused small but significant increases in ICP
      at 0.5, 1.0 and 1.5 MAC, but there were no changes with sevoflurane. However,
      sevoflurane caused a considerable decrease in MAP with consequent decrease in
      CPP. We conclude that sevoflurane should be a suitable agent for neuroanaesthesia
      and is preferable to either enflurane or halothane.

PMID- 8260307
TI  - Problems associated with tracheal extubation.

PMID- 8260308
TI  - Anaesthesia for carotid artery surgery.

PMID- 8260309
TI  - Continuous subcutaneous infusion of morphine--an alternative to extradural
      morphine for postoperative pain relief.
AB  - In a randomized, double-blind study of 40 patients undergoing total abdominal
      hysterectomy, we have compared continuous subcutaneous infusion (CSCI) of
      morphine with discontinuous extradural injection of morphine for postoperative
      analgesia at rest and during cough. The CSCI group received a bolus of morphine
      0.1 mg kg-1 i.v. at the end of the operation and continued with s.c. infusion of
      morphine 30 micrograms kg-1 h-1. The extradural group received morphine 4 mg
      extradurally at 0, 2, 10 and 18 h after operation. Pain and side effects were
      evaluated at 2, 4, 8, 12 and 24 h after operation. In the extradural group,
      significantly smaller pain-scores were observed both at rest and during cough
      compared with the CSCI group. No significant difference was observed between the
      groups regarding supplementary doses of morphine, peak expiratory flow values or
      side effects. We conclude that morphine by CSCI is not as effective as morphine
      injected extradurally. However, CSCI seems to provide simple and relatively
      effective analgesia with a low rate of side effects.

PMID- 8260310
TI  - Deep body temperature during the warming phase of cardiopulmonary bypass.
AB  - We have compared deep body temperature (DBT) measured at the forehead with the
      core temperatures of the nasopharynx, oesophagus and rectum during the warming
      phase of cardiopulmonary bypass (CPB) (moderate hypothermia of 26.7-29.6 degrees
      C) in 12 patients. DBT was measured transcutaneously by an insulated thermistor
      probe that created an area of zero thermal flow between skin and subcutaneous
      tissue. The core temperatures measured at different sites lagged behind the
      increase in arterial blood temperature during warming. The trend was most marked
      with rectal temperature and least with oesophageal temperature. Among all
      measurements, the closest linear relationship was found between forehead DBT and
      nasopharyngeal core temperature (0.99 x nasopharyngeal temperature (degrees C) 
      0.07; SEE = 0.53; r = 0.99; P < 0.0001). Forehead DBT measurement may be useful
      as a reliable non-invasive method of monitoring cerebral temperature during CPB.

PMID- 8260311
TI  - Haemodynamic effects of propofol during coronary artery bypass surgery.
AB  - We have studied the haemodynamic effects of a bolus injection of propofol 2 mg kg
      1 in 20 patients with good ventricular function undergoing aortocoronary bypass
      surgery. Heart rate and systolic and diastolic systemic (SAP, DAP) and pulmonary
      arterial pressures, central venous pressure, pulmonary artery wedge pressure,
      cardiac output (CO), right ventricular ejection fraction, systemic (SVR) and
      pulmonary vascular resistances and left ventricular stroke work index (LVSWI)
      were measured before and at 1, 3, 5, 10, 20 and 30 min after the administration
      of propofol. At 1 min, maximum decreases were detected in SAP (-26%, P < 0.001),
      DAP (-17%, P < 0.001), SVR (-22% P < 0.001) and LVSWI (-23%, P < 0.001). The
      other variables studied showed no significant variations at any time during the
      study. We conclude that propofol reduces systemic arterial pressure by a decrease
      in SVR, but not in CO or ventricular filling pressures.

PMID- 8260312
TI  - Failure to wean from cardiopulmonary bypass after myocardial revascularization:
      successful treatment with verapamil via the aortic root.
AB  - Severe ventricular dysfunction in a patient prevented weaning from
      cardiopulmonary bypass after myocardial revascularization. Calcium chloride and
      increasing doses of dopamine had no effect. Coronary vasospasm was diagnosed
      based on ST elevation and myocardial failure. Verapamil 0.5 mg, injected into the
      aortic root, was followed by a dramatic improvement in cardiac contractility and
      successful weaning from cardiopulmonary bypass without inotropic support.

PMID- 8260313
TI  - Surgical emphysema and upper airway obstruction complicating recovery from
      anaesthesia.
AB  - We describe a case of surgical emphysema and life-threatening airway obstruction
      resulting from a small pharyngeal perforation. The perforation apparently
      resulted from the use of a Yankauer-type sucker after uneventful anaesthesia for
      stapedectomy.

PMID- 8260314
TI  - Resistance to constant air flow imposed by the standard laryngeal mask, the
      reinforced laryngeal mask and RAE tracheal tubes.
AB  - The reinforced laryngeal mask airway (RLMA) has been introduced recently for head
      and neck surgery. Its resistance to constant air flow has been measured and
      compared with that of the standard laryngeal mask airway (LMA). The RLMA
      resistance has also been compared with that imposed by the standard oral Ring
      Adair-Elwyn (RAE) tube of a corresponding size for a given patient. The
      resistance to gas flow of the new RLMA was approximately three to five times that
      of the LMA at two flow rates (0.5 and 1.0 litre s-1). The resistance of the RLMA
      4 was intermediate between that of RAE tubes sizes 8 and 9 mm, and that of RLMA 2
      intermediate between that of RAE tubes sizes 5 and 6 mm.

PMID- 8260315
TI  - Efficacy of therapeutic suggestions presented during anaesthesia: re-analysis of
      conflicting results.
AB  - Re-analysis has been made of two clinical studies which used similar
      methodologies but found different effects of so-called therapeutic suggestions
      presented to anaesthetized patients undergoing abdominal hysterectomy. The re
      analysis suggested that when data from the two studies were examined jointly, it
      was uncertain if positive suggestions had a reliable influence upon the recovery
      measure of "days to discharge". The supposed positive effect reported in one of
      the studies may arise from a rather different distribution of data in the control
      group. It is proposed that the effect may be attributable to chance bias in
      allocation of patients to the control group, or to some other chance anomaly in
      the composition of the group as a result of relatively small sample size. The
      importance of sample size is discussed in relation to detection of effects when
      only a few patients may be in a state susceptible to intra-anaesthetic
      suggestions. The importance of presenting data distributions in addition to
      summary statistics is also emphasized.

PMID- 8260316
TI  - Why do anaesthetists need codes?
AB  - With the increasing availability of information technology in hospitals and the
      introduction of medical audit and resource management, there is a proliferation
      of anaesthetic data collection systems. The amount of data recorded varies from a
      complete anaesthetic record to a small subset of it. Most systems hold data in
      coded form for reasons of accuracy and compactness. Unfortunately, all the coding
      systems are different, making comparisons between different centres difficult. We
      propose that there is a need to develop a standard national system for coding
      anaesthetic terms.

PMID- 8260317
TI  - Comparison of two measurements.

PMID- 8260318
TI  - Hepatotoxicity of volatile anaesthetic agents.

PMID- 8260319
TI  - Pressor response to venous cannulation.

PMID- 8260320
TI  - Pressor response to venous cannulation.

PMID- 8260321
TI  - Topographic mapping of human motor cortex with transcranial magnetic stimulation:
      Homunculus revisited.
AB  - The purpose of this study was to non-invasively evaluate the homuncular
      organization of the motor cortex in man. We used transcranial magnetic
      stimulation to induce motor evoked potentials (MEP's) in Abductor Pollicis Brevis
      (APB) and Biceps Brachii (BB) muscles of 10 healthy volunteers. The practicality
      and accuracy of magnetic stimulation to scalp sites one cm apart was increased by
      the application to the scalp of a flexible nylon grid with grid size of 1x1 cm.
      Responsive scalp sites collectively contributed to distinct but overlapping
      muscle representational areas for the two muscles. The topography of these motor
      maps along and slightly anterior to the central fissure corresponds to the
      homuncular configuration as described by Penfield and Boldrey in 1937.

PMID- 8260322
TI  - Computerized pattern recognition of EEG artifact.
AB  - Automated artifact classification of quantified EEG (QEEG) epochs from 9 males
      using linear discriminant analysis showed greater than 85% agreement with judges'
      opinions. These results were replicated (n = 600 epochs for each sample). Testing
      the entire sample (n = 5800) illustrated reliable eye artifact (94%) but reduced
      muscle artifact classification (70%) accuracy. Agreement was lowest in the case
      of more subtle forms of muscle artifact (i.e., low amplitude muscle), however,
      less than 4% of these were wrongly classified as non-artifact. Improved data
      collection techniques retaining high frequency energies are anticipated to
      improve muscle artifact recognition. Results indicate that low levels of artifact
      contamination would result when only those epochs classified as non-artifact were
      accepted for inclusion in further analysis.

PMID- 8260323
TI  - Comparison of single current dipole and magnetic field tomography analyses of the
      cortical response to auditory stimuli.
AB  - Measurements of the magnetic field elicited by a 50 ms long auditory stimulus,
      from three normal subjects and one head injured subject, are used to estimate the
      three dimensional distribution of generators in the brain. The resulting images
      are compared with point source solutions obtained with the usual single current
      dipole fitting procedures, over a latency range which includes the extrema in the
      (average) measured signal. In all cases considered, 100 or so epochs time-locked
      to the stimulus were magnetically recorded. These were averaged, and then
      analyzed using two techniques; a new distributed current model known as Magnetic
      Field Tomography (MFT), and the standard single current dipole (SCD) model. Both
      methods provide estimates of the current generators in the brain. In two of the
      normal subjects, the MFT solutions are super-imposed onto Magnetic Resonance
      Images (MRI) of the relevant cortical area. The results show that when the SCD
      model provides a reasonable description of the data, the MFT estimate shows one
      dominant localized region in agreement with the current dipole position. In the
      MFT sequence of solutions the activity evolves smoothly; multiple areas of
      activity often arise as the focal activity in one region declines while focal
      activity in another region grows. In contrast the SCD solutions during these
      intermediate periods fit the data poorly, and may move erratically from one
      locale to another. We conclude that MFT seems to provide a reasonable description
      of the activity through cortical and subcortical regions. The evolution of
      activity, as derived from the average signal, can be traced continuously from the
      onset of the stimulus, not just at the peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260324
TI  - An application of autoregressive model to pattern discrimination of brain
      electrical activity mapping.
AB  - Using the autoregressive model, we developed a method of illustrating significant
      regional differences between two records of brain electrical activity mapping.
      This new approach of brain electrical activity mapping analysis through a
      statistical taxonomy may be clinically useful for evaluation of the normal
      development of EEG in children and for localizing functional brain abnormality.

PMID- 8260325
TI  - Event-related potentials in complex partial seizures.
AB  - Both early (N1 and P2) and late (N2 and P3) event-related potentials (ERP) were
      obtained in 16 patients with complex partial seizures, 12 with left hemispheric
      ictal focus and 4 with right, to see if they help in lateralizing the seizure
      focus, and also to determine if they correlate with behavioral (MMPI, Bear
      Fedio), attentional (Trails A and B), cognitive (WAIS-R, Boston Naming,
      Warrington Word and Face recognition) and mental speed (Stroop color naming and
      reading) tasks. Early waves were more often lateralized than late waves but both
      were often falsely lateralizing. Early waves were better correlated with
      behavioral tasks whereas late waves were better with those measuring mental
      speed, attention and cognition. These data tentatively discourage the utility of
      ERP in preoperative lateralization of seizure focus but argue for their potential
      value in psychophysiological correlations.

PMID- 8260326
TI  - Spatio-temporal progression of the AEP P300 component using the cortical imaging
      technique.
AB  - The cortical imaging technique (CIT), a mathematical method for simulating the
      potential fields on the surface of the brain, was used to analyze the spatio
      temporal progression of the AEP P300 component (as well as the preceding and
      subsequent N2a and N3 components) from thirty normal adult subjects recorded in a
      standard "oddball" paradigm. Comparisons were made between the progressions of
      the endogenous event-related cognitive potentials and the exogenous stimulus
      dependent potentials (N1 component). Cortical imaging results suggest that
      different and multiple generator sites are involved in the production of
      exogenous and endogenous evoked responses. We particularly note the asymmetric
      development of the P300 component and the apparent anterior generator sites for
      the N2a component. This last result is interesting because the N2a precedes the
      P300 component and supports an earlier frontal contribution.

PMID- 8260327
TI  - Ocular artifacts in EEG and event-related potentials. I: Scalp topography.
AB  - The ocular artifacts that contaminate the EEG derive from the potential
      difference between the cornea and the fundus of the eye. This corneofundal or
      corneoretinal potential can be considered as an equivalent dipole with its
      positive pole directed toward the cornea. The cornea shows a steady DC potential
      of approximately +13 mV relative to the forehead. Blink potentials are caused by
      the eyelids sliding down over the positively charged cornea. The artifacts from
      eye-movements result from changes in orientation of the corneo-fundal potential.
      The scalp-distribution of the ocular artifacts can be described in terms of
      propagation factors--the fraction of the EOG signal at periocular electrodes that
      is recorded at a particular scalp location. These factors vary with the location
      of the scalp electrode. Propagation factors for blinks and upward eye-movements
      are significantly different.

PMID- 8260328
TI  - Ocular artifacts in recording EEGs and event-related potentials. II: Source
      dipoles and source components.
AB  - The source dipoles for blinks point radially whereas the source dipoles for
      saccades point tangentially, in the direction of the eye movement. This indicates
      that blink potentials are not generated by eye movements but by the eyelid
      sliding down over the positively charged cornea. Dipole source dipole analysis
      shows that the "rider artifact" at the onset of upward and lateral saccades is
      caused by the eyelid as it lags a little behind the eyes at the beginning of the
      movement. Dipole source analysis allows both the EEG and the EOG to be modeled
      simultaneously and EOG generators to be distinguished from nearby EEG generators.
      Ocular source components can be calculated from a principal component analysis of
      EEG and EOG recordings during blinks and saccades. The effectiveness of
      propagation factors, source dipoles and source components in removing ocular
      artifacts from EEG samples was assessed. The most effective correction procedure
      uses source components.

PMID- 8260329
TI  - Inverting a Laplacian topography map.
AB  - There are some occasions when it is better to use the Laplacian of the scalp
      voltages (e.g., for topographic displays and dipole source localization) and
      other occasions when it is better to use the original voltages (e.g., for
      comparison to non-Laplacian topography maps). This paper presents a simple
      algorithm for going between these two representations of the data. The inverse
      Laplacian involves iterative feedback. An Excel spreadsheet implementation of the
      algorithm is presented.

PMID- 8260330
TI  - GUSTO: is science or money talking?

PMID- 8260331
TI  - Positive pressure breathes new life into non-invasive ventilation.

PMID- 8260332
TI  - The long-term safety and tolerability of transdermal glyceryl trinitrate, when
      used with a patch-free interval in patients with stable angina.
AB  - The safety and tolerability of intermittent (16 hours on/8 hours off) nitrate
      patch therapy (0.2, 0.4 or 0.6 mg/hr: dose adjusted as required) was studied for
      a median duration of 356 days in 106 patients (mean age 60.9 +/- 8.6 years) with
      angina pectoris. Most patients (82%) were on existing beta-blocker and/or calcium
      antagonist therapy. Safety, tolerability and efficacy data were obtained by means
      of patient diary cards and regular clinic visits. Almost 90 treatment years
      revealed no significant or serious adverse events, and there were no changes in
      haematology or biochemistry associated with intermittent nitrate patch therapy.
      The most frequently reported side-effects were headache, skin reactions and
      dizziness (53%, 20% and 8% of patients respectively). Treatment resulted in a
      sustained reduction in the frequency and severity of angina attacks, reduced
      sublingual GTN consumption, an improvement in general wellbeing and a rise in the
      proportion of patients in whom angina was controlled.

PMID- 8260333
TI  - Practical cardiological skills and ECG interpretation amongst doctors.

PMID- 8260334
TI  - Investigation of colonic symptoms: the value of flexible sigmoidoscopy.
AB  - Colonic symptoms and large-bowel disease are common in elderly people, but the
      optimum investigative schema is not well established. Double-contrast barium
      enema (DCBE) and full colonoscopy share several drawbacks; both require colonic
      preparation which at best causes stool frequency and urgency, at worse
      dehydration and hypovolaemia. Many physicians feel that in the elderly this
      represents such a risk that inpatient preparation is preferred. Both
      investigations may involve much discomfort and distress. Rigid sigmoidoscopy is
      the traditional first colonic examination in patients with colonic symptoms, but
      will detect fewer than 10% of significant colonic lesions. Further investigation
      is almost always needed in elderly patients.

PMID- 8260335
TI  - Helicobacter pylori prevalence in a routine upper gastrointestinal endoscopy
      population.
AB  - The presence of Helicobacter pylori (HP) in gastric biopsy specimens of 500
      patients referred for routine upper gastrointestinal endoscopy for various
      abdominal complaints was investigated histologically and microbiologically. HP
      was detected in 429 of the 500 patients (86%). Antral biopsy specimens revealed
      gastritis in 457 out of 500 cases (91.4%). In the 43 patients who had normal
      histological findings, only 3 had HP infection (7%). The prevalence of HP in the
      patients with gastric and duodenal ulcers was 91%. In 95.6% of the ulcer
      patients, biopsy specimens showed gastritis. There was a statistically
      significant rise in the prevalence of HP with age. The correlation between
      histologic and microbiologic diagnostic methods was good. This study shows that
      HP positivity and gastritis are common in a routine endoscopy population and that
      there is a strong association between H. pylori, gastritis and peptic ulcer
      disease.

PMID- 8260336
TI  - Occult malignancy is associated with venous thrombosis unresponsive to adequate
      anticoagulation.
AB  - The increased incidence of intravascular thrombosis and thromboembolic episodes
      in patients with malignant disease is well documented. There have, however, been
      only two reports of covert malignancy in patients who continue to extend their
      deep vein thrombosis despite apparently adequate anticoagulation. Three patients
      are described in whom venous thrombosis steadily worsened despite a prothrombin
      time of at least twice normal. None had either obvious predisposing factors to
      thromboembolism or a family history of thrombotic disease. Recognition of this
      phenomenon can be helpful in avoiding delay in diagnosing malignancy in young
      patients.

PMID- 8260337
TI  - Ramstedt's pyloromyotomy: a specialist procedure?
AB  - One hundred and twenty infants with infantile hypertrophic pyloric stenosis were
      operated on by two consultant general surgeons over a 13-year period. General
      anaesthetic and a standard surgical approach was used in all cases. No mortality
      was recorded and there were no wound dehiscences. The overall postoperative wound
      infection rate was 9.2%. Prior to 1985 the infection rate was 15%. Following
      attention to a number of details including care of the umbilicus, the incidence
      decreased after 1985 to 4%. The most common postoperative complication was
      vomiting, which occurred in 25% of infants. There was one negative laparotomy in
      the 13-year study period. Two children required a second procedure for persistent
      vomiting. The argument in favour of specialisation in managing this condition is
      questioned along with the need for intensive diagnostic investigation.

PMID- 8260338
TI  - Potential for bed sores due to high pressures: influence of body sites, body
      position, and mattress design.
AB  - Pressures were measured on 10 subjects, supine and sitting, under six anatomical
      sites prone to bed sores on three different mattresses. Studied were the
      Clinifloat and Therarest specialist replacement mattresses, and a standard
      hospital mattress. Mean supine pressures were less than 5 kPa under four sites.
      Average supine buttock pressure was 2.93 kPa. Occiput and heel pressures were
      much higher than under other sites, being on average 2.6 and 4.5 times greater
      respectively than the mean buttock pressure. On sitting up, buttock pressure
      increased by a factor of 1.7 on average, to a level higher than the accepted
      capillary closing pressure. Measurements were consistent with mattress design,
      specific features of which can significantly affect pressure under certain sites.

PMID- 8260339
TI  - Thymopentin prophylactic treatment in patients with recurrent respiratory
      infections.
AB  - Present immunological methods do not regularly detect abnormalities in patients
      with chronic bronchitis, and no single parameter appears to be closely associated
      with the clinical findings. Of the many tests performed in the cited studies, the
      Merieux multitest procedure seems to offer the best findings in further studies,
      followed by determination of the OKT4/OKT8 ratio. The theoretical background for
      the use of an immunologic approach to prevent frequent recurrences of infections
      is discussed in depth, with particular emphasis on the pharmacologic efficacy
      profile of thymopentin. The safety of this drug is remarkably unproblematic. The
      present survey of 11 clinical studies shows that thymopentin treatment reduces
      the incidence of recurrent respiratory tract infections. The most frequently used
      dosing regimen is 50 mg SC three times a week for 6 weeks, which may be repeated
      after 3-6 months. The clinical effect appears long-lasting, ie, 3-4 months after
      discontinuation of treatment.

PMID- 8260340
TI  - The use of sumatriptan in the treatment of migraine.
AB  - Sumatriptan is a selective agonist of 5-hydroxytryptamine receptors, recommended
      for the acute treatment of migraine. The 5-HT1 receptor subtype is found in the
      cranial vasculature of many species including humans, and causes vasoconstriction
      of these vessels. Sumatriptan as a highly potent 5-HT1 agonist selectively
      constricts large intracranial blood vessels and also blocks neurogenic
      inflammation. Those treating patients with severe or inconveniently timed attacks
      will find sumatriptan the drug of choice.

PMID- 8260341
TI  - The incidence of abdominal aortic aneurysms.
AB  - The incidence of abdominal aortic aneurysms (AAAs) is increasing, especially in
      the elderly. This trend has been observed in the United Kingdom, USA, Australia,
      and Sweden. The increase can be explained partly by an enhanced awareness of the
      condition and partly by the rising numbers of elderly in the population. In
      addition, improved diagnostic techniques have enabled earlier detection of
      aneurysms. But this does not fully explain why we are seeing such a high
      prevalence of the condition. Evidence for the increase can be obtained from a
      number of sources, such as routine mortality statistics.

PMID- 8260342
TI  - To run or not to run? That is the question: exercise and reduced risk of coronary
      heart disease.
AB  - The recent National Fitness Survey has drawn attention to the population's low
      level of physical (aerobic) fitness and low level of activity. About one-third of
      middle-aged men and one-half of middle-aged women in England are unfit for
      continuous walking at a normal pace of about 3 mph. Similar fitness levels were
      shown for the Welsh population. At the same time, coronary heart disease (CHD)
      accounts for about 26% of deaths in England, and for 2.5% of the NHS expenditure.
      The suggestion that low fitness levels and low levels of physical activity are
      associated with a high incidence of CHD has been widely voiced since Morris's
      first study, and has more recently been the subject of editorials in the British
      Heart Journal and the BMJ.

PMID- 8260343
TI  - Tuberculous peritonitis presenting as coloenteric fistula.
AB  - Abdominal tuberculosis can present as tuberculous peritonitis with generalised or
      loculated ascites, lymphadenitis of the mesenteric or retroperitoneal nodes, or
      as intestinal tuberculosis. In the last case it could be annular mucosal
      ulceration, single or multiple strictures or hyperplastic tuberculosis of the
      bowel, usually involving the terminal ileum or ileocaecal region. Disease higher
      in the ileum is considered common but involvement of the appendix, stomach,
      duodenum, jejunum, colon and rectum is unusual. Tuberculous peritonitis
      presenting as a coloenteric fistula is not a common clinical entity. In this case
      a patient who presented with peritonitis was found to have tuberculous
      peritonitis with coloenteric fistula.

PMID- 8260344
TI  - Increased nail and hair growth in a patient with AIDS.
AB  - A variety of nail and hair changes have been described in AIDS patients, but
      rapid nail growth has not previously been reported. A slowing of nail growth
      would be expected in these patients due to immunosuppression and possible
      malnutrition. We report a case of increased nail and hair growth in a man with
      AIDS.

PMID- 8260345
TI  - Surgical presentation of toxic shock syndrome.
AB  - Three infants with clinical features of sepsis, hypovolaemia and an acute abdomen
      were referred to a paediatric surgical unit. Subsequent clinical signs of diffuse
      macular erythema followed by desquamation and isolation of Staphylococcus aureus
      from nasal or umbilical swabs led to a diagnosis of staphylococcal toxic shock
      syndrome. Surgical intervention was not indicated.

PMID- 8260346
TI  - A rare late complication of breast cancer treatment.
AB  - In 1948 Stewart and Treeves recognised and described six cases of
      lymphangiosarcoma arising in the oedematous upper limb of patients who had
      previously undergone radical mastectomy and radiotherapy for breast carcinoma.
      The incidence of lymphangiosarcoma in such patients is 0.45% and is uniformly
      aggressive and fatal, with a 5-year survival of less than 5% regardless of the
      treatment modality. We present a case report to increase the clinical awareness
      of this rare and fatal iatrogenic complication occurring subsequent to breast
      cancer treatment, and speculate on ways of improving survival.

PMID- 8260347
TI  - Treatment of adult pyloric stenosis: a pharmacological alternative?
AB  - Patients presenting with gastric outlet obstruction require investigation and
      treatment by surgery or balloon dilatation. This paper presents three cases of
      classic pyloric stenosis due to long-standing scarring from peptic ulceration.
      All cases were planned for active intervention but all settled, while
      investigations were in progress, with omeprazole. This would suggest that there
      are increasing numbers of such patients who are temporised with this treatment
      but may present again with refractile pyloric stenosis.

PMID- 8260348
TI  - Obstructive jaundice due to intracholedochal blood clot: an unusual early
      presentation of primary hepatic carcinoma.
AB  - We report a case of early presentation of a hepatocellular carcinoma with
      obstructive jaundice, due to obstruction of the common bile duct by a blood clot.
      The possibility of preoperative diagnosis, the surgical treatment and the
      postoperative outcome are discussed.

PMID- 8260349
TI  - Problems in diagnosis and management of hypovolaemia in spinal injury.
AB  - Thoracic spinal cord injury can result in hypotension from loss of peripheral
      vascular tone. There may be problems in both diagnosis and management when this
      is combined with hypovolaemia from haemorrhage. A case is reported that
      illustrates these difficulties.

PMID- 8260350
TI  - Cervical radiculopathy: pancoast tumour?

PMID- 8260351
TI  - Fluvoxamine and SIADH.

PMID- 8260352
TI  - Therapeutic trials in vaginal candidosis.

PMID- 8260353
TI  - Accelerated malignant disease in pregnancy.

PMID- 8260354
TI  - Stopping rules, interim analyses and data monitoring committees.

PMID- 8260355
TI  - Molecular genetic aspects of human cancers: the 1993 Frank Rose Lecture.

PMID- 8260356
TI  - 31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma
      xenograft lines: tumour bioenergetic status and blood supply.
AB  - Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice were subjected
      to 31P-nuclear magnetic resonance (31P-NMR) spectroscopy in vivo. The following
      resonances were detected: phosphomonoesters (PME), inorganic phosphate (Pi),
      phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma,
      alpha and beta (NTP gamma, alpha and beta). The main purpose of the work was to
      search for possible relationships between 31P-NMR resonance ratios and tumour pH
      on the one hand and blood supply per viable tumour cell on the other. The latter
      parameter was measured by using the 86Rb uptake method. Tumour bioenergetic
      status [the (PCr + NTP beta)/Pi resonance ratio], tumour pH and blood supply per
      viable tumour cell decreased with increasing tumour volume for five of the six
      xenograft lines. The decrease in tumour bioenergetic status was due to a decrease
      in the (PCr + NTP beta)/total resonance ratio as well as an increase in the
      Pi/total resonance ratio. The decrease in the (PCr + NTP beta)/total resonance
      ratio was mainly a consequence of a decrease in the PCr/total resonance ratio for
      two lines and mainly a consequence of a decrease in the NTP beta/total resonance
      ratio for three lines. The magnitude of the decrease in the (PCr + NTP
      beta)/total resonance ratio and the magnitude of the decrease in tumour pH were
      correlated to the magnitude of the decrease in blood supply per viable tumour
      cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the
      magnitude of this decrease was larger for the tumour lines showing a high than
      for those showing a low blood supply per viable tumour cell. No correlations
      across the tumour lines were found between tumour pH and tumour bioenergetic
      status or any other resonance ratio on the one hand and blood supply per viable
      tumour cell on the other. The differences in the 31P-NMR spectrum between the
      tumour lines were probably caused by differences in the intrinsic biochemical
      properties of the tumour cells rather than by the differences in blood supply per
      viable tumour cell. Biochemical properties of particular importance included rate
      of respiration, glycolytic capacity and tolerance to hypoxic stress. On the other
      hand, tumour bioenergetic status and tumour pH were correlated to blood supply
      per viable tumour cell within individual tumour lines. These observations suggest
      that 31P-NMR spectroscopy may be developed to be a clinically useful method for
      monitoring tumour blood supply and parameters related to tumour blood supply
      during and after physiological intervention and tumour treatment. However,
      clinically useful parameters for prediction of tumour treatment resistance caused
      by insufficient blood supply can probably not be derived from a single 31P-NMR
      spectrum since correlations across tumour lines were not detected; additional
      information is needed.

PMID- 8260357
TI  - In vivo therapeutic potential of combination thiol depletion and alkylating
      chemotherapy.
AB  - The effect of administering the thiol modulating agent buthionine sulfoximine
      (BSO) in conjunction with alkylating chemotherapy was investigated in vivo in the
      mouse KHT sarcomas and bone marrow stem cells. Tumour response to treatment was
      assessed by an in vivo to in vitro excision assay and bone marrow survival was
      determined in vitro by CFU-GM. Glutathione (GSH) depletion and recovery kinetics
      were determined at various times after treatment using high performance liquid
      chromatography (HPLC) techniques. Following a single 2.5 mmol kg-1 dose of BSO,
      tumour GSH reached a nadir of approximately 40% of control 12-16 h after
      treatment. Bone marrow GSH was depleted to approximately 45% of control 4-8 h
      after treatment but recovered to normal by 16 h. When a range of doses of CCNU,
      mitomycin C, cyclophosphamide or melphalan (MEL) were given 16 h after mice were
      exposed to a 2.5 mmol kg-1 dose of BSO, only the antitumour efficacy of MEL was
      effectively enhanced (by a factor of approximately 1.4). This BSO-MEL combination
      appeared to be selective for the tumour as the bone marrow toxicity was not
      increased beyond that seen for MEL alone. Since increasing the administered dose
      of BSO neither increased the extent of thiol depletion in the tumour nor enhanced
      the antitumour efficacy of MEL, three other protocols for delivering the thiol
      depletor were explored. BSO was given either as multiple 2.5 mmol kg-1 doses
      administered at 6 or 16 h intervals or continuously at a concentration of 30 mM
      supplied in the animals' drinking water. Both multi-dose BSO pretreatments were
      found to increase both the antitumour efficacy and normal tissue toxicity of MEL
      such that no advantage compared to the single dose combination was achieved. In
      contrast, maintaining the thiol depletor in the drinking water led to an
      approximately 1.7-fold increase in the antitumour efficacy of MEL without any
      corresponding increase in bone marrow stem cell toxicity. For the various
      pretreatment strategies it was possible, in all cases, to account for the
      presence or absence of a net therapeutic benefit on the basis of the tumour and
      bone marrow GSH depletion and recovery kinetics.

PMID- 8260358
TI  - Selective cellular acidification and toxicity of weak organic acids in an acidic
      microenvironment.
AB  - The mean extracellular pH (pHe) within solid tumours has been found to be lower
      than in normal tissues. Agents which cause intracellular acidification at low pHe
      might have selective toxicity towards cells in tumours. Weak acids (or their
      anions) with pKa values in the range of 4-6 have a higher proportion of molecules
      in the uncharged form at low pHe and can diffuse more rapidly into cells. The
      effects of organic acids including succinate, monomethyl succinate and malonate
      to acidify cells have been evaluated under conditions of different pHe in the
      acidic range. These weak acids caused intracellular acidification of murine EMT-6
      and human MGH-U1 cells in a concentration and pHe dependent fashion. At
      concentrations of 10 mM and above, these acids also caused in vitro cytotoxicity
      to these cells at low pHe (< 6.5). The rate and extent of cellular acidification
      caused by these weak acids, and their cytotoxicity at low pHe, were enhanced by
      exposure to amiloride and 5-(N-ethyl-N-isopropyl)amiloride (EIPA), agents which
      inhibit Na+/H+ exchange, and hence the regulation of intracellular pH. Acid
      dependent cytotoxicity was also investigated in a murine solid tumour using the
      endpoints of growth delay and colony formation in vitro following treatment in
      vivo. Agents were tested alone or with 15 Gy X-rays to select a population of
      hypoxic (and presumably acidic) cells. Achievable serum concentrations of
      succinate were about 1 mM and no antitumour activity of succinate was detected
      when used in this way. It is concluded that weak acids are selectively taken up
      into cells, and can cause selective cellular acidification and toxicity, at low
      pHe in culture. Weak acids that are normal cellular metabolites are not toxic in
      vivo, but weak acids carrying cytotoxic groups offer the potential for selective
      uptake and toxicity under the conditions of low pHe that exist in many solid
      tumours.

PMID- 8260359
TI  - cDNA transfection followed by the isolation of a MCF-7 breast cell line resistant
      to tamoxifen in vitro and in vivo.
AB  - A tamoxifen resistant cell line (clone 9) has been isolated from the tamoxifen
      sensitive, hormone responsive MCF-7 breast carcinoma cell line after transfection
      with mixed cDNA libraries, followed by tamoxifen selection in the presence of
      oestrogens. Transfection was confirmed by Southern analysis with vector probes.
      Clone 9 in several-fold more resistant to tamoxifen and other anti-oestrogens
      than wild type cells when cultured either as a monolayer or as colonies in soft
      agar but retains oestrogen receptors. Clone 9 was less responsive to 17-beta
      oestradiol than were wild type MCF-7. In addition to showing in vitro tamoxifen
      resistance, clone 9 was also tamoxifen resistant in vivo when xenografted into
      the nude mouse. Culture medium conditioned by clone 9 cells stimulated quiescent
      cells of the same clone as well as wild type cells, whereas medium conditioned by
      wild type MCF-7 was inhibitory to both, suggesting that clone 9 may be secreting
      an autocrine growth factor. Clone 9 provides a novel model for further
      investigation of the mechanism of anti-oestrogen resistance that occurs without
      loss of oestrogen receptors. Preliminary results suggest that an autocrine growth
      stimulatory mechanism may be one pathway of such resistance.

PMID- 8260360
TI  - Cell kinetic analysis of murine squamous cell carcinomas: a comparison of single
      versus double labelling using flow cytometry and immunohistochemistry.
AB  - The study was originally set up to measure accurate cell kinetic parameters in
      two murine squamous cell carcinomas (scc) for comparison with radiobiological
      data on proliferation during radiotherapy. The tumours, AT84 and AT478, were both
      moderately well differentiated aneuploid scc. In the course of the study, several
      comparisons of techniques were made in two different centres. This paper reports
      on the results of those comparisons involving two different detection methods
      (flow cytometry and immunohistochemistry), single vs double labelling, and in
      vivo and in vitro labelling, the latter using tissue slices incubated under high
      pressure oxygen. Pulse labelling studies with bromodeoxyuridine (BrdUrd) showed
      that the labelling indices (LI) were not significantly different after in vitro
      or in vivo labelling. In addition, the flow cytometry (FCM) and
      immunohistochemistry (IHC) methods also gave labelling indices which were not
      significantly different. Only tumour cells were analysed in these studies by
      selecting cells on the basis of aneuploidy (FCM) or morphology (IHC). The DNA
      synthesis time of the tumour cells were analysed by both techniques. For FCM, the
      Relative Movement method was used (Begg et al., 1985). For IHC, a double
      labelling method was used, employing BrdUrd and triated thymidine (3H-TdR)
      administered several hours apart, detected simultaneously using immunoperoxidase
      and autoradiography, respectively. When both labels were administered in vivo,
      there was good agreement for Ts between the FCM and IHC methods. Attempts were
      also made to measure Ts in vitro using both techniques. With double labelling, it
      was found that cells did not take up the second label, implying a failure of
      cycle progression. This was confirmed by FCM results, showing no movement of
      labelled cells through the S-phase, despite an initially high uptake. This could
      not be influenced by lowering the DNA precursor concentration or by adding foetal
      calf serum. This indicates that DNA synthesis times are difficult or impossible
      to measure in vitro in fresh tumour explants. Finally, the double labelling IHC
      method allowed intratumoural variations of both LI and Ts to be studied. Both
      parameters were found to vary markedly throughout the tumour volume, particularly
      for larger tumours (600 mg), giving calculated local potential doubling time
      values (Tpot) ranging from 1-7 days.

PMID- 8260361
TI  - The effects of pentoxifylline on the relative perfusion of tumours growing in
      three sites in the mouse.
AB  - The haemorheological agent pentoxifylline (PTX) has been shown to improve the
      relative perfusion and oxygenation of subcutaneous tumours in the mouse. In order
      to establish whether this effect is dependent on the site of tumour growth, we
      have looked at changes in the distribution of the cardiac output (COD) to the
      murine NT carcinoma grown either intradermally (i.d.), intramuscularly (i.m.), on
      the wall of the caecum, or in all three sites, following i.p. administration of
      50 mg kg-1 PTX. In animals bearing a single tumour, PTX treatment significantly
      increases the COD to tumours located in the caecum, but has no significant effect
      on the COD to those located in the i.d. or i.m. sites. If all three tumours are
      present in a single animal, the COD to all three tumours is significantly
      enhanced by PTX. This appears to reflect the presence of the caecum tumour and
      does not appear to relate to changes in tumour size or to the haematocrit (HCT)
      of the blood. We propose that this site dependency implies that a significant
      increase in blood viscosity only occurs in animals with tumours located in
      specific sites. Therefore, the potential radiosensitising capability of PTX is
      highly dependent on tumour location.

PMID- 8260362
TI  - Pharmacokinetics of varying doses of nicotinamide and tumour radiosensitisation
      with carbogen and nicotinamide: clinical considerations.
AB  - Plasma concentrations, after administration of varying doses of nicotinamide,
      were measured in CBA male mice using a newly-developed high performance liquid
      chromatography assay. In all dose groups, peak levels were observed within the
      first 15 min after an i.p. administration of 0.1, 0.2, 0.3 or 0.5 mg g-1 of
      nicotinamide. There was a clear dose-dependent increase in plasma concentration
      with increasing dose, with almost a five-fold lower concentration (1.0 vs 4.9
      mumol ml-1) achieved with a dose of 0.1 mg g-1 compared with 0.5 mg g-1,
      respectively. The half-life of nicotinamide increased from 1.4 h to 2.2 h over
      the dose range (P < 0.01). Comparisons with previous pharmacokinetic data in
      humans show that clinically-relevant oral doses of 6 and 9 g in humans give
      plasma levels slightly higher than those achieved at 1 h with doses of 0.1 to 0.2
      mg g-1 in mice. Tumour radiosensitisation with carbogen alone, and with carbogen
      combined with varying doses of nicotinamide (0.05 to 0.5 mg g-1), was
      investigated using a 10-fraction in 5 days X-ray schedule. Relative to air
      breathing mice, a statistically significant increase in sensitisation was
      observed with both a local tumour control and with an in vivo/in vitro excision
      assay (P < or = 0.007). With the local control assay, a trend was observed
      towards lower enhancement ratios (ERs) with decreasing nicotinamide dose (from
      1.85 to 1.55); carbogen alone was almost as effective as when combined with 0.1
      mg g-1 of nicotinamide. With the excision assay, ERs for carbogen combined with
      nicotinamide increased with decreased levels of cell survival. At a surviving
      fraction of 0.02, enhancement ratios of 1.39-1.48 were obtained for carbogen plus
      0.1 to 0.3 mg g-1 of nicotinamide. These were lower than those seen with the two
      higher doses of 0.4 to 0.5 mg g-1 (ERs = 1.63-1.69).

PMID- 8260363
TI  - Inhibition of pancreatic cancer cell growth in vitro by the tyrphostin group of
      tyrosine kinase inhibitors.
AB  - Tyrphostins are a group of low molecular weight synthetic inhibitors of protein
      tyrosine kinases (PTK). The intracellular domains of the receptors for epidermal
      growth factor (EGF), transforming growth factor-alpha (TGF-alpha), insulin-like
      growth factor 1 (IGF-1) possess PTK activity. Since EGF, TGF-alpha and IGF-1 are
      considered to play an important role in the proliferation of pancreatic cancer
      cells, we studied the effects of tyrphostins on the growth of three human
      pancreatic cancer cell lines (MiaPaCa-2, Panc-1 and CAV). The tyrphostins AG17,
      T23 and T47 all inhibited EGF and serum-stimulated DNA synthesis. AG17 was found
      to be the most potent of these agents and caused a dose-dependent but reversible
      inhibition of cell growth. Furthermore using an immunoblotting procedure we also
      found AG17 to inhibit EGF-induced tyrosine phosphorylation in the MiaPaCa-2 cell
      line. Tyrosine kinase inhibitors may prove to be useful agents for the treatment
      of pancreatic cancer.

PMID- 8260364
TI  - Susceptibility to apoptosis is differentially regulated by c-myc and mutated Ha
      ras oncogenes and is associated with endonuclease availability.
AB  - Oncogenes and oncosuppressors can deregulate cell replication in tumours, and
      recently have been shown to influence the probability of apoptosis. The effects
      of human c-myc and mutated (T24) Ha-ras oncogenes on susceptibility to apoptosis
      were investigated by introducing them into immortalised rat fibroblasts. The
      resulting family of transfectants showed closely similar measures of
      proliferation, but widely divergent rates of apoptosis, differing by up to
      fifteen-fold, that correlated inversely with population expansion rates in vitro.
      T24-ras transfectants with moderate or high p21ras expression showed reduced
      apoptosis, and this was reversed by pharmacological inhibition of membrane
      localisation of p21ras by mevinolin. In contrast, c-myc stimulated apoptosis, and
      this was further enhanced by serum deprivation. Inducibility of effector proteins
      represents one possible mechanism of genetic control of the susceptibility to
      apoptosis, and its investigation showed that c-myc was associated with expression
      by viable cells of latent calcium/magnesium sensitive endonuclease activity
      characteristic of apoptosis. In contrast, endonuclease activity was not detected
      in viable cells of a T24-ras transfectant expressing high levels of p21ras. Thus,
      there appeared to be differential regulation of susceptibility to apoptosis,
      positively by c-myc and negatively by activated ras, and this was associated with
      availability of endonuclease activity. Genetic modulation of apoptosis in human
      neoplasms is likely to influence net growth rate, retention of cells acquiring
      new mutations and response to certain chemotherapeutic agents.

PMID- 8260366
TI  - Further study of nebulisation chemotherapy, a new chemotherapeutic method in the
      treatment of lung carcinomas: fundamental and clinical.
AB  - Nebulisation chemotherapy, a chemotherapeutic method for the treatment of lung
      cancer that involves the administration of anticancer agents through the
      inhalation of nebulised aerosols, has been found to be highly effective
      (Tatsumura et al., 1983a,b). We confirmed that 5-FU administered by this method
      accumulates in the trachea, bronchi and regional lymph nodes of patients treated
      before surgery, along with 5-FU metabolites, FUR and FUdR, indicating that 5-FU
      is directly incorporated and metabolised in the respiratory tract. Parallel
      result were obtained using mongrel dogs. The 5-FU levels in other organs, such as
      the heart and liver, were found to be extremely low. Only a trace of 5-FU was
      found in the serum of both the patients and the dogs. We further investigated the
      anti-tumour effect of this therapy in ten selected patients and observed a
      satisfactory anti-tumour response of 60.0%. These results, along with our
      previous finding that the retention time of isotope tracers inhaled as aerosol is
      considerably longer in tumour tissues than in normal parts (Tatsumura et al.,
      1983a) explain the high antitumour action of this therapy and the absence of
      adverse effects of administered 5-FU.

PMID- 8260365
TI  - p53 expression and its relationship to DNA alterations in bone and soft tissue
      sarcomas.
AB  - The p53 gene is one of the best studied tumour suppressor genes. Recently we
      performed mutation analysis on the p53 gene in a large number of bone and soft
      tissue sarcomas, and found that approximately one-third of the sarcomas have some
      type of DNA alteration at the p53 locus (Toguchida et al., 1992). However, the
      expression of the p53 protein resulting from these alterations still remains to
      be clarified. In this study, p53 expression in the sarcoma tissues was analysed
      immunohistochemically using antibody PAb421 (Oncogene Science) and its
      relationship to DNA alterations was examined. Of 113 tumours, 29 (25.7%) showed
      positive staining for the p53 protein. These included 19 of 67 osteosarcomas,
      five of 20 chondrosarcomas, four of 11 malignant fibrous histiocytomas (MFHs) and
      one Ewing's sarcoma. In chondrosarcomas, most of the p53-positive tumours
      belonged to highly malignant and atypical tumour types (dedifferentiated or
      mesenchymal type), suggesting a role for p53 mutation in the progression of
      cartilaginous tumours. All the cases with a missense mutation showed strongly
      positive staining, while no immunoreactivity was observed in the remaining three
      quarters with DNA alterations including gross rearrangement, frame-shift
      mutation, nonsense mutation or mutation at splicing site except in one case.
      These results demonstrated the dominance of the p53 mutations with null protein
      expression in bone and soft tissue sarcomas, showing a unique characteristic of
      these types of tumours compared with other malignancies such as colon carcinomas.

PMID- 8260367
TI  - A randomised trial of three or six courses of etoposide cyclophosphamide
      methotrexate and vincristine or six courses of etoposide and ifosfamide in small
      cell lung cancer (SCLC). I: Survival and prognostic factors. Medical Research
      Council Lung Cancer Working Party.
AB  - A total of 458 eligible patients, from 21 centres, with histologically or
      cytologically confirmed SCLC were allocated at random to three chemotherapy
      regimens, each given at 3-week intervals. In two regimens, etoposide,
      cyclophosphamide, methotrexate and vincristine were given for a total of either
      three courses (ECMV3) or six courses (ECMV6). In the third regimen, etoposide and
      ifosfamide were given for six courses (EI6). Patients with limited disease (56%
      of the total) also received radiotherapy to the primary site after the third
      course of chemotherapy in all three groups. A partial response occurred in 45% of
      144 ECMV3 patients, 48% of 141 ECMV6, and 53% of 141 EI6 patients assessed, and a
      complete response in a further 15%, 9%, and 13% respectively, giving total
      response rates of 60%, 57%, and 67%, respectively. There was no overall survival
      advantage to any of the three regimens. At 1 year, 24%, 29%, and 30% of patients
      were alive, and at 2 years 7%, 8%, and 9%, respectively. The median survival time
      was 7.4 months in the ECMV3 group, 8.6 months in the ECMV6 group and 8.8 months
      in the EI6 group. The individual factors: poor performance status, extensive
      disease, the presence of dysphagia and a raised white blood cell count on
      admission adversely affected prognosis. The results do not exclude the
      possibility of a minor survival advantage with the two 6-course regimens. The
      findings on quality of life are presented in the companion paper (MRC Lung Cancer
      Working Party, 1993b).

PMID- 8260368
TI  - A model of long-term survival following adjuvant therapy for stage 2 breast
      cancer.
AB  - Following adjuvant therapy for breast cancer, some patients will die of this
      tumour while the remainder will die of other causes. Deaths from breast cancer
      tend to follow a lognormal distribution, while deaths from other causes can be
      approximated by national demographic data. By combining these two survival
      models, we have generated an age-specific method for estimating the impact of
      treatment on overall long-term survival. Treatment was designed to operate by one
      of two mechanisms: an increase in cured fraction, or an increase in median tumour
      related survival time among uncured patients. This analysis revealed that, for
      young and middle-aged patients, an increase in cured fraction has substantially
      greater long-term clinical impact than an increase in median survival time.
      Unfortunately, the non-parametric tests traditionally used in prospective
      clinical trials cannot distinguish between these two mechanisms of action.

PMID- 8260369
TI  - A simulated sequential analysis based on data from two MRC trials.
AB  - The motivation for proposing sequential methods for cancer clinical trials is
      presented, and the methodology examined by re-analysing two completed phase III
      cancer trials of the Lung Cancer Working Party of the British Medical Research
      Council. The reanalysis proceeds as if the trials had been designed with a
      planned series of interim analyses governing stopping. Specifically, the
      triangular and double-triangular tests were applied. The sequential reanalysis
      gave a substantial reduction in the number of patient required, and deaths
      observed, for conclusions to be reached in comparison with the completed studies.
      In each case, the sequential analysis was stratified for baseline prognostic
      factors which were seen to be important at the first interim analysis.

PMID- 8260370
TI  - Interim analyses and stopping rules in cancer clinical trials.
AB  - A clinical trial conducted according to a schedule of interim analyses written
      into the protocol, and stopped according to a predetermined rule, is known to
      statisticians as a sequential clinical trial. This methodology is becoming more
      widely used in trials concerning life-threatening diseases because of its ability
      to adjust the sample size to the emerging information on treatment efficacy. When
      treatments under comparison differ appreciably, small samples will be sufficient;
      for more subtle differences larger numbers of patients need to be recruited.
      Sequential methods have already been used in certain cancer clinical trials, and
      they are especially appropriate for such studies. In this paper the principles of
      sample size determination are reviewed, and the essential aspects of designing
      sequential trials are described. The necessity for a special form of statistical
      analysis following a sequential trial is explained, and the consequences of early
      or late stopping on the analysis are investigated. Compromises which have to be
      made between the formal requirements of theory and the practical realities of
      trial conduct are discussed.

PMID- 8260371
TI  - A phase-III study of recombinant interleukin 2 and 5-fluorouracil chemotherapy in
      patients with metastatic colorectal cancer.
AB  - Sixteen patients with metastatic colorectal cancer have been treated with a
      regimen involving an 120 h continuous infusion of rIL-2, 18 x 10(6) iu m-2 day
      followed by three injections of 5FU 600 mg m-2 at weekly intervals. Entry
      criteria included no previous chemotherapy, ambulatory performance status, and a
      measurable lesion. In most cases side effects were easily manageable and only one
      patient required transfer to an intensive care unit with the capillary leak
      syndrome. In three patients persistent hypotension was found to be unrelated to
      treatment with rIL-2, being caused respectively by a line infection, pulmonary
      embolus, and bowel perforation. This last proved a fatal complication. Five
      patients (33%; [95% confidence limits, 11.8%-61.6%]) achieved a partial response,
      and two non-responders later achieved a partial response when treated with weekly
      5FU. This regimen is currently being evaluated in a phase-III randomised
      controlled trial.

PMID- 8260372
TI  - A randomised study of carboplatin vs sequential ifosfamide/carboplatin for
      patients with FIGO stage III epithelial ovarian carcinoma. The London
      Gynaecologic Oncology Group.
AB  - In a study designed to compare response rates of patients with stage III
      epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 patients were
      randomised to receive either sequential therapy with three cycles of ifosfamide
      followed by three cycles of carboplatin, or to six cycles of single agent
      carboplatin. Ifosfamide was given every 3 weeks in a dose of 5 gm m-2 as a 24 h
      infusion with mesna, 1 gm m-2 by i.v. bolus prior to ifosfamide, 3 gm m-2 with
      ifosfamide, and 1 gm m-2 as an 8 h infusion after ifosfamide. Carboplatin was
      given in a dose of 400 mg m-2 by short i.v. infusion every 4 weeks. Sixty-eight
      evaluable patients were randomised to sequential ifosfamide/carboplatin, and 67
      to single agent carboplatin. Median follow-up is 36 months (range 5.5-82.3).
      After three cycles of treatment two patients in the ifosfamide/carboplatin arm
      achieved complete remission (CR), and 12 partial remission (PR) for an overall
      response rate of 29%, whereas in the carboplatin arm ten patients achieved CR,
      and 23 PR, for an overall response rate of 63% (P = 0.0008). Seven of 15 patients
      with progressive disease, and nine of 20 patients with stable disease at the
      initial response evaluation, following three cycles of ifosfamide, subsequently
      responded to carboplatin therapy so that the final response rate to the complete
      regimen was 65% for the ifosfamide/carboplatin arm, compared to 71% for the
      carboplatin arm (NS). For the ifosfamide/carboplatin arm, median recurrence free
      survival and overall survival were 14.1 months and 18.7 months. Corresponding
      figures for the carboplatin arm were 14.5 months and 21.5 months (NS). Both
      treatments were generally well tolerated. However 47% of patients in the
      ifosfamide/carboplatin arm developed alopecia sufficient to require a wig,
      compared to only 2% in the carboplatin arm. Ifosfamide is clearly less effective,
      and more toxic than carboplatin. Ifosfamide failures can however be effectively
      salvaged by subsequent carboplatin treatment. Ifosfamide cannot be recommended
      for single agent therapy in ovarian carcinoma, however the combination of
      carboplatin plus ifosfamide might be a suitable treatment to be tested in a
      future randomised study against carboplatin alone.

PMID- 8260373
TI  - Micronutrients in gastrointestinal cancer.
AB  - The monitoring of micronutrients and the relationship between dietary intake and
      micronutrient status prior to and after surgery in patients with histologically
      proven gastrointestinal adenocarcinoma, both weight-stable and weight-losing (>
      7.5% of their pre-illness weight) has been studied and the results compared to
      controls. Plasma vitamin C and red blood cell thiamine levels were significantly
      lower in weight-losing cancer patients when compared to their weight-stable
      counterparts (P < 0.05 and P < 0.02 respectively). Weight-losing patients had a
      lower vitamin C (P < 0.05) and thiamine (P < 0.002) intake, and a higher
      elevation in plasma C-reactive protein and a lower prealbumin level (P < 0.02),
      when compared to both weight-stable cancer patients and controls. Plasma vitamin
      C, prealbumin and C-reactive protein levels remained unchanged after curative
      resections of the tumours compared to a preoperative value, and there was a
      highly significant correlation between plasma vitamin C and dietary intake of
      vitamin C. This study suggests that the lower vitamin C and thiamine status in
      weight-losing gastrointestinal cancer patients prior to surgery is due to a lower
      micronutrient intake and an acute phase response to their illness. Dietary intake
      of vitamin C appears to be the major factor in determining plasma vitamin C
      concentration following curative surgical resection.

PMID- 8260374
TI  - Testicular function following the treatment of Hodgkin's disease in childhood.
AB  - Testicular function was studied in 40 males treated in childhood for Hodgkin's
      disease at St Bartholomew's Hospital, and the Hospital for Sick Children, London,
      between 1971-1985. All patients were 16 years or over at evaluation, and off
      treatment more than 6 years. Basal FSH, LH and testosterone levels were measured.
      Testicular size was measured using a Prader orchidometer, and all patients were
      offered a seminal analysis. Twenty-eight patients were treated with chemotherapy,
      usually ChlVPP. Twenty-one also had radiotherapy, five below the diaphragm.
      Twelve patients were treated with radiotherapy alone (five below the diaphragm).
      Twenty-six of 28 patients treated with chemotherapy and three of five patients
      treated with radiotherapy alone below the diaphragm have elevated basal FSH
      levels, and 18 of these also have elevated basal LH levels. Median testicular
      volume is 11 ml (range 5-25 ml). Eleven of 13 patients investigated are
      azoospermic. All patients have normal testosterone levels, and normal secondary
      sexual characteristics. There is no biochemical evidence of healing of the
      damaged germinal epithelium with elevated FSH levels persisting up to 17 years
      from the end of therapy. These results indicate a high incidence of damage to the
      germinal epithelium in patients treated with ChlVPP chemotherapy and/or
      radiotherapy below the diaphragm. Appropriate counselling of these patients with
      regard to their reproductive capabilities is essential.

PMID- 8260375
TI  - Multicentre cross over study of aminoglutethimide and trilostane in advanced
      postmenopausal breast cancer.
AB  - Trilostane and Aminoglutethimide, each given with a physiological replacement
      dose of hydrocortisone, were randomly allocated to 72 eligible postmenopausal
      advanced breast cancer patients; following treatment failure on either drug the
      patient continued with the other drug, if in a suitable clinical condition.
      Thirty-eight patients initially received Trilostane of whom 19 subsequently
      received Aminoglutethimide; 34 patients initially had Aminoglutethimide and seven
      of these then received Trilostane. Both groups of patients were comparable in all
      respects. There was no difference in the objective response rate to either drug,
      Trilostane 11/38 = 29%, Aminoglutethimide 12/34 = 35%, nor in the average time to
      disease progression for the two drugs, Trilostane 64 weeks, Aminoglutethimide 68
      weeks. Of the 26 patients who received both drugs, four showed a response to both
      suggesting no cross resistance. Side effects were seen to both drugs in
      approximately half of the patients, but were mainly gastro-intestinal with
      Trilostane and rash and drowsiness with Aminoglutethimide. There was no evidence
      of cross over patient susceptibility to side effects.

PMID- 8260376
TI  - Early stage cervical cancer: psychosocial and sexual outcomes of treatment.
AB  - Eighty-three women, mean age 45 years, successfully treated by surgery (S) or
      radiotherapy (RT) for stage 1b cervical cancer were assessed a mean of 97 weeks
      post treatment. Forty to 50% reported persistent tiredness, lack of energy and
      weight gain. Sixty per cent had not resumed their full premorbid functional
      status. Mean scores for anxiety and depression were higher than general
      population means and this sample scored higher for psychological distress than
      published data quoted for disease free cancer patients. These women reported many
      concerns about cervical cancer, most commonly fear of recurrent disease (91%).
      More than one-third blamed themselves for the disease. There were no significant
      differences in functional outcome or psychological status between treatment
      groups or by age or time since treatment. Psychological distress scores were
      significantly correlated with physical complaints (P < 0.001) and functional
      outcomes (P < 0.02). For the 61 women who were sexually active, sexual function
      post-treatment was rated as significantly poorer than subjectively recalled
      premorbid sexual function (P < 0.005). RT treated patients were more likely to
      report pain on intercourse and loss of enjoyment. Psychological as well as
      physical problems were highly correlated with sexual outcome (P < 0.01) 44% were
      unable to talk adequately with their partners about their experience. The
      majority felt they needed more information about cervical cancer, its treatment
      and how to help themselves rehabilitate. Forty-nine per cent would have liked to
      have had counselling. Even with the same physical morbidity the functional,
      emotional and sexual status of these women could be improved by giving more
      attention to their psychological and sexual concerns.

PMID- 8260377
TI  - Serum lactate dehydrogenase level as a prognostic factor in Hodgkin's disease.
AB  - The efficacy of currently available treatments for Hodgkin's disease (HD) has led
      to a substantial modification in the prognosis of this disease; nevertheless
      there is still a group of patients that cannot be cured with conventional
      treatments and who will be candidates for alternative therapy. In the present
      work we analysed the prognostic influence of the most relevant clinico-biological
      characteristics of HD in a consecutive series of 137 patients diagnosed and
      treated in a single institution. Univariate analyses identified six variables
      with significant prognostic influence, both on achieving complete remission (CR)
      and overall survival (OS); LDH > 320 U ml-1, age > 45 years, stages IIB, III and
      IV, extranodal involvement, alkaline phosphatase > 190 UI dl and ESR > 40 mm h.
      In addition, Hb < 12.5 gr dl-1 and abdominal disease were statistically relevant
      for CR while a poor performance score (ECOG > or = 2) affected a lower survival.
      In the multivariate analysis only LDH, age and the clinical stage retained a
      significant prognostic influence for achieving CR, while the two first factors
      above, together with performance status were the variables with independent
      prognostic value with respect to OS. Moreover, only LDH > 320 U ml-1 had
      prognostic influence in the probability of relapse and disease free survival
      (DFS), both in the univariate and multivariate analyses. According to the three
      independent factors obtained in the multivariate analysis for CR (LDH, age and
      stage) a predictive model was established that allows the stratification of
      patients into two prognostic groups: one with poor prognosis that includes
      patients with the three adverse prognostic factors, or two if one of them was
      elevated LDH, and the other with good prognosis that includes the remaining
      patients. This model was also able to separate two independent groups of patients
      with respect to OS and to DFS. In conclusion, the present study shows that LDH is
      one of the most important prognostic factors in HD.

PMID- 8260378
TI  - Are plant factors a missing link in the evolution of endemic Burkitt's lymphoma?
AB  - Burkitt's lymphoma, an Epstein-Barr virus (EBV)-associated non-Hodgkin's
      malignant lymphoma is endemic in an area of Africa known as the Lymphoma Belt.
      This zone is demarcated by climatic requirements of temperature and rainfall. EBV
      activating plant factors are among several co-factors which have been proposed
      for the development of epidemic Burkitt's Lymphoma (eBL). The distribution of
      Euphorbia tirucalli, a plant which possesses EBV-activating substances and can
      induce the characteristic 8:14 translocation of eBL in EBV-infected lymphoblastic
      cell lines in vitro, conforms closely to the climatic requirements of the
      Lymphoma. This plant, other EBV-activating plants and plants of unknown EBV
      activating status with medicinal uses, are found significantly more often at the
      homes of eBL patients in Malawi than in those of controls. The possible role of
      these plant factors in the pathogenesis of eBL and their routes of bodily access
      are discussed. It is postulated that the associations described in this paper
      provide support for the theory that EBV-activating plants are co-factors involved
      in the pathogenesis of some cases of eBL.

PMID- 8260379
TI  - Cancer in the population of Hanoi, Vietnam, 1988-1990.
AB  - The first results from the population-based cancer registry for the city of
      Hanoi, in northern Vietnam, are presented. In men, incidence rates are moderate
      low with the most common cancers being lung, stomach and liver. Cancer of the
      penis, reportedly very common in early case series from Vietnam, is now rarely
      seen. In women, incidence rates are low with the most common cancer, breast
      cancer, having a recorded incidence similar to that in China. Cervix cancer
      incidence is very low, which contrasts strongly with hospital series from the
      south of Vietnam, and of 30 years earlier in Hanoi. The incidence of
      choriocarcinoma is high, and that of nasopharynx cancer (in both sexes)
      moderately so; both findings are typical of southeast Asian populations. The
      incidence rates are coherent with the results from recent studies of Vietnamese
      migrants in the USA and UK.

PMID- 8260380
TI  - Multiple primary tumours in a population-based series of patients with
      histopathologically peer-reviewed sarcomas.
AB  - Multiple primary tumours occurring in a three-year population-based series of
      patients with histopathologically peer-reviewed sarcomas from North West England
      were ascertained in order to look at the patterns of neoplasms seen. A total of
      30 out of the 310 patients entered in the study had additional primary tumours.
      Very few patients were aged under 60 years at diagnosis of both their
      malignancies. The youngest was a known case of neurofibromatosis and, although
      seven patients were diagnosed with a sarcoma and carcinoma of the breast--a
      combination of cancers characteristic of the Li-Fraumeni cancer family syndrome-
      no other patients could directly be identified as suffering from any other cancer
      predisposition syndrome.

PMID- 8260381
TI  - Trends in breast cancer incidence in Sweden 1958-1988 by time period and birth
      cohort.
AB  - Statistics from the Swedish National Cancer Registry based on all 110,658 cases
      of invasive breast cancer during the 31-year period 1958-1988 were analysed. Age
      specific incidence rates increased over successive calendar periods. The average
      annual increase in the age-standardised incidence rate was 1.3%, with the
      greatest percentage changes among the youngest age groups. During the latter half
      of the study period, the rates of increase tended to diminish in the youngest age
      groups and even reversed significantly among women from 75 years of age. In
      analyses using age-period-cohort models, the best fit of the cancer incidence
      data was found for the full model which simultaneously considered the effects of
      age, period and cohort. Cohort effects were found to be more important than
      period effects, in terms of model fit. These effects emerged as a seemingly
      consistent, and in a logarithmic scale, fairly linear increase in the relative
      risk of breast cancer incidence with a 3-fold elevation in women born in the
      1950's relative to those born in the 1880's. It is concluded that the rising
      breast cancer incidence in Sweden is explained chiefly by birth cohort effects,
      which indicate persistent secular changes in largely unknown risk factors
      associated with life style. We could not in the present data see any clear
      evidence for an adverse effect of contraceptive or replacement sex steroids on
      breast cancer incidence.

PMID- 8260382
TI  - A plea for better coding rules for bladder cancer.

PMID- 8260383
TI  - Calculating the risk.

PMID- 8260384
TI  - NHS reforms: making it better.

PMID- 8260385
TI  - Solving incontinence through assessment.
AB  - Urinary incontinence is a major problem in many nursing homes, and is often
      poorly managed. The author describes the attempts of one nursing home to address
      the problem by piloting a simple assessment and management programme. Many of the
      causes of incontinence were easily corrected and nurses' level of satisfaction
      increased as a result.

PMID- 8260387
TI  - Patient education: post-operative needs.
AB  - The need for nurses to participate in health education is much emphasised, and
      yet nursing literature identifies that this activity still presents problems for
      nurses. This article reports on a case study approach to researching the
      provision of patient education on a short-stay surgical ward. The study found
      that of the ten patients studied, satisfaction was generally high, but
      expectations of being informed and of participating in care were generally low.
      The nursing staff were committed to patient education, and felt prepared for the
      task, but tended to restrict themselves to information-giving or advice-giving
      approaches which were not always effective. Patient education was not always
      documented.

PMID- 8260388
TI  - Empowering nurses in a practical way.
AB  - Practical approaches to increasing autonomy and participation will be required to
      underpin the rhetoric of 'empowerment', says James Buchan in his monthly column.

PMID- 8260386
TI  - Mental health: financial arrangements for long-stay residents.
AB  - The process of preparing long-stay patients for relocation from mental health
      hospitals to the community has been well described, but little attention has been
      paid to the effects such a move has on arrangements for residents' finances. This
      article describes a system which seemed to mix the best of the traditional
      hospital banking system with modern community-based commercial banking services,
      and how the provision of a financial service to a group of institutionalised
      residents assisted in the process of re-personalisation.

PMID- 8260390
TI  - Women's network. A woman's place is....

PMID- 8260389
TI  - The effectiveness of continuing education.
AB  - Continuing education will survive and prosper in the NHS market-place, the author
      argues, if it is seen to be the 'fittest' for its purpose--the delivery of
      effective quality care demonstrated through the enhanced performance of nurses.
      She proposes that evidence of such fitness can be gained through a
      multidimensional evaluation framework that allows the interaction of relevant
      factors to be mapped; estimated and used as a performance indicator.

PMID- 8260391
TI  - The Standard guide to the referring of written articles.

PMID- 8260392
TI  - Invidious performance reviews.

PMID- 8260393
TI  - University challenge.

PMID- 8260394
TI  - Computer reviews. Get organised--on the cheap.

PMID- 8260395
TI  - Heart health (continuing education credit).
AB  - Promoting heart health is an important component of preventive health care today.
      It involves health promotion issues which potentially fall within the remit of
      every practising nurse, such as helping clients to reduce blood pressure and
      blood cholesterol levels, weight, stress, salt and alcohol intake, and to stop
      smoking.

PMID- 8260397
TI  - Residential care: the deregulation debate continues.

PMID- 8260398
TI  - Cardiovascular assessment (continuing education credit).

PMID- 8260396
TI  - Freeing the system.

PMID- 8260399
TI  - HIV/AIDS: consulting outpatients to improve services.
AB  - The authors discuss how a simple survey was used to elicit patients' views of an
      HIV/AIDS outpatient clinic, and how their results have relevance for all nurses
      interested in developing care and services, irrespective of the clinical setting
      in which they work. The main findings were that patients liked the clinic's
      informal atmosphere, but many were dissatisfied with its organisation and waiting
      times. Awareness was also raised among staff about the difficulties that patients
      who had jobs experienced in trying to attend the clinic.

PMID- 8260400
TI  - Integrating services in community child care.
AB  - Many changes in education and practice are taking place which will affect
      paediatric nurses working in the community. The authors argue that instead of
      fighting over professional boundaries and defending traditional territories,
      nurses involved in community child care must learn to integrate their services.
      They urge nurses to make the most of opportunities being presented to them to
      develop a high-quality professional service.

PMID- 8260401
TI  - Sister Susie. Send in the SWOT squad.

PMID- 8260402
TI  - One minute wisdom. Mental Health Act section orders could be more effectively
      policed.

PMID- 8260404
TI  - Workwise. Sneaky peaky.

PMID- 8260403
TI  - Information technology: computers kill care.

PMID- 8260405
TI  - Is it ration all?

PMID- 8260406
TI  - Tissue viability. Pressure sore prevention: scoring pressure sore risk in the
      community.
AB  - To help combat the risk of patients developing pressure sores while being nursed
      at home, a new risk calculator has been researched and designed by the wound care
      specialist and members of the Walsall District Nursing Research Group. This
      article traces the development of the score and highlights its advantages for
      assessing the risk of pressure sores in the community.

PMID- 8260407
TI  - Tissue viability. Post-operative wounds: a nurse-led change in wound dressings.
AB  - In an attempt to ascertain whether the type of dressing used in hip replacement
      surgery can affect the risk of patients haemorrhaging post-operatively, a survey
      was carried out on a 25-bedded orthopaedic ward. It was found that thinly dressed
      wounds were more likely to lead to haemorrhage. As a result of this nursing-led
      initiative, the consultants agreed to use thickly padded dressings and there has
      since been a reduction in the number of patients haemorrhaging.

PMID- 8260408
TI  - Isolation of HIV/mental health nurses.

PMID- 8260409
TI  - Students: the soft drug approaches.

PMID- 8260410
TI  - Health promotion: the waiting game.

PMID- 8260411
TI  - Community placement: establishing links.
AB  - Many strategies are required in the development of the community placement to
      ensure a learning environment is established which can meet the needs of students
      on traditional EN conversion, undergraduate and Project 2000 courses. In this
      first of two articles, the process of establishing a community clinical links
      team is discussed. The development and evaluation of an audit tool specifically
      designed for use within the community will be discussed in the second article
      next week.

PMID- 8260412
TI  - Protocols: guidance for good practice.
AB  - The use of standardised protocols in patient care is becoming widespread. They
      offer a positive adjunct to nurses, but can be misused by managers to effect
      changes in staffing skill mix. This article offers guidance for nurses on the
      essential criteria a protocol must achieve before being considered acceptable.

PMID- 8260414
TI  - The adolescent in accident & emergency.
AB  - The needs of adolescent patients attending accident and emergency departments may
      not be recognised by nurses due to ignorance of the nature of adolescent
      development, and prejudice over perceived self-injurious behaviours. The author
      unravels some of the mysteries behind the motivating forces of adolescent
      behaviours, and offers guidance to nurses who may be caring for what is
      understood to be a 'difficult' patient group.

PMID- 8260413
TI  - Pride and prejudice.

PMID- 8260415
TI  - Nurses' attitudes to patient activation.
AB  - Levels of engagement of patients in rehabilitation activities in elderly care
      wards tend to be low, despite evidence that activity improves functional
      recovery. Since most patients in such wards spend their day in the direct care of
      nurses, an activation programme was established in a Liverpool elderly care unit.
      Informally, nurses expressed general feelings of satisfaction with the programme,
      but some disquiet was also noted. A survey of their attitudes towards the patient
      activation programme was therefore undertaken. No significant differences were
      found between the attitudes of nurses according to grade or between experimental
      and control wards, but a significant difference was noted between each of the
      four wards when regarded as independent variables. These findings suggest the
      need for 'ownership' of developments in rehabilitation care.

PMID- 8260417
TI  - Dunce?

PMID- 8260418
TI  - Cardiology update. Cardiogenic shock.

PMID- 8260416
TI  - Community care: the ideal home inhibition.

PMID- 8260419
TI  - Nurses call for review of HIV education.

PMID- 8260420
TI  - Cardiology update. Intra-aortic balloon pumps.

PMID- 8260421
TI  - Cardiology update. Drug therapy.

PMID- 8260422
TI  - Cardiology update. Hyperbaric oxygen therapy.

PMID- 8260423
TI  - Myths on the rocks: using and abusing alcohol (continuing education credit).

PMID- 8260424
TI  - [Facial clefts].

PMID- 8260425
TI  - [Poisonous and less poisonous plants. 11].

PMID- 8260427
TI  - [Acute kidney failure--nursing tasks in conservative therapy].

PMID- 8260426
TI  - [Drug therapy and its problems in epilepsy].

PMID- 8260428
TI  - [Kinesthesis--infant handling. Conscious perception, conscious movement,
      conscious encouragement and support].

PMID- 8260429
TI  - [Holistic care--concerning a premature/newborn department and general comments].

PMID- 8260430
TI  - [Gerhard Domagk (1895-1964)].

PMID- 8260431
TI  - Histopathological determinants of survival in resected cases of pancreas cancer.
AB  - We have examined the histopathological factors affecting the degree of local
      spread, regional lymph node (RLN) metastases, and overall survival (O.S.) in a
      group of 39 cases of resected carcinoma of the exocrine pancreas. Although the
      mean O.S. for the group was 14.3 months, resected patients without RLN
      involvement had a mean survival of 24 months. In contrast the mean O.S. rate was
      8 months for patients with RLNs involved. Size, tumor location, and histological
      grade were compared to RLN involvement and O.S. The mean size of primary tumor
      did not differ significantly between patients with or without RLN's (r.1 versus
      4.6 cms). However, 7 or 8 T1 tumors were < 4 cm and 35% of tumors < 4 cm were T1
      lesions. In contrast, only 1 of 17 tumors (6%) > 4 cm was T1. Histological grade
      was correlated with nodal status and O.S. There was a significant difference
      between histological grade and the presence of metastatic lymph nodes (G1, 37%
      positive, G2-4.50% positive). Patients with well differentiated tumors had a mean
      survival of 21 months compared to a mean survival of 10 months for less
      differentiated tumors (p < 0.05). This difference was even more significant when
      stratified for nodal status. The patients with well differentiated tumors and no
      RLN involvement had a mean survival of 32.5 months compared to 8.6 months for
      well differentiated tumors with RLN involvement. In summary, we have shown that
      size, histological grade, and local spread predict for nodal status. However,
      specific patient subsets (G1, node negative) may exhibit an excellent survival
      when curative pancreas resection is successful.

PMID- 8260432
TI  - Monocyte secretion of beta-hexosaminidase in patients with obstructive jaundice.
AB  - Monocyte hydrolases are harmful when secreted inappropriately. In this study we
      have investigated the levels of one of the hydrolases. beta-hexosaminidase in
      patients with obstructive jaundice. These patients showed markedly elevated
      plasma levels, and their monocytes show increased spontaneous secretion and total
      enzyme content. The plasma enzyme levels correlate with monocyte enzyme content
      as well as bile salt, and bilirubin levels, the high levels may also reflect
      Kupffer cell damage, as these cells clear the enzyme. Compared with controls
      monocytes from jaundiced patients show reduced enzyme secretion after PMA
      stimulation, in vitro, and unchanged secretion after zymosan stimulation. There
      is a difference between plasma enzyme levels in benign and malignant patients but
      this does not provide a clear distinction between the two groups. We conclude
      that patients with obstructive jaundice have increased blood level of beta
      hexosaminidase, and that activated monocytes partly contribute to this change.

PMID- 8260433
TI  - Pilot study on alcohol-induced chemonecrosis of hepatic metastases from colonic
      cancer. A new approach for percutaneous localized dynamic destruction of the
      hepatic spread.
AB  - Administration of 98% ethanol destroys tissues by coagulative necrosis. In the
      rat bearing 1,2-dimethylhydrazine-induced colonic carcinoma which has spread to
      the liver, direct injection of 0.1-0.2 ml ethanol into each of the hepatic
      metastases at the time of total colectomy afforded a significant survival
      advantage relative to colectomy alone (20.1 +/- 0.2 vs 12.8 +/- 0.2 months of
      age, mean +/- SEM, n = 20, p < 0.01 by the Mann-Whitney U test). A pilot study
      was, therefore, carried out (2 women and 4 men, age range 43 to 71 years--mean
      56) to examine the clinical significance of these observations in patients with
      multiple hepatic metastases from carcinoma of the sigmoid colon. The tumour was
      resected then all palpable hepatic secondaries were injected with 1-1.5 ml of 98%
      ethanol. Two weeks post-operatively and thereafter once every two months any
      hepatic lesions detected ultrasonically were similarly treated percutaneously.
      All the patients tolerated this treatment without any observed distress or
      adverse effects. Their mean survival measured from the time of tumour resection
      until death from any cause was 20 months (range 17 to 26 months). The survival
      gain afforded by chemonecrosis in addition to its simplicity and safety deserves
      further consideration to assess the exact role of this method in the treatment of
      liver metastases from colonic cancer.

PMID- 8260434
TI  - Factors relating to coagulation, fibrinolysis and hepatic damage after liver
      resection.
AB  - A survey of the blood of twenty-two patients who had undergone hepatic resection
      was performed. Serum levels of alpha-2 plasmin inhibitor-plasmin complex
      initially decreased from 1.58 +/- 0.31 microgram/ml on the preoperative day
      (PREOP), to 0.92 +/- 0.14 mu/ml on the first postoperative day (POD 1), and then
      increased to 3.13 +/- 0.92 micrograms/ml on the seventh postoperative day (POD 7)
      (mean +/- SE)). Thrombin-anti-thrombin III complex (14.2 +/- 4.3 ng/ml on PREOP
      and 26.0 +/- 4.1 ng/ml on POD 7 (mean +/- SE)) and D-dimer (335 +/- 96 ng/ml on
      PREOP and 1859 +/- 258 ng/ml on POD 7 (mean +/- SE)) increased in the early
      postoperative stage. The level of 6-keto-prostaglandin F1 alpha increased after
      the operations (from 13.2 +/- 1.8 pg/ml on PREOP to 37.8 +/- 12.8 pg/ml on POD 7
      (mean +/- SE)). The level of thromboxane B-2 decreased at first, and then
      gradually increased and returned to its preoperative level on POD 7 (144.7 +/-
      43.8 pg/ml on PREOP, 57.6 +/- 27.5 pg/ml on POD 1 and 152.5 +/- 58.4 pg/ml on POD
      7 (mean +/- SE)). Superoxide dismutase activity increased at first, and then
      gradually decreased, postoperatively (2.8 +/- 0.5 NU/ml on PREOP, 4.8 +/- 0.8
      NU/ml on POD 1 and 2.6 +/- 0.3 NU/ml on POD 7 (mean +/- SE)). That is,
      biodefensive reactions which protect patients against the shift to disseminated
      intravascular coagulation (DIC) were inferred with by the increase in
      antiplatelet aggregation, despite the activation of coagulation and fibrinolytic
      mechanisms after hepatic resection.

PMID- 8260435
TI  - Portal hypertension, variceal bleeding, and high output cardiac failure secondary
      to an intrahepatic arterioportal fistula.
AB  - Intrahepatic arterioportal fistulas (APF) are uncommon complications following
      hepatic trauma. Large fistulas can result in portal hypertension and
      cardiovascular compromise. A 46-year-old patient is described who presented with
      portal hypertension, variceal bleeding, and high output cardiac failure due to a
      large intrahepatic APF. Surgical closure of the APF by hepatic resection
      successfully resolved the portal hypertension, prevented further variceal
      hemorrhage, and restored normal cardiovascular function.

PMID- 8260436
TI  - Partial cholecystectomy--safe and effective.
AB  - Patients undergoing surgical treatment for calculous disease were considered to
      have had a partial cholecystectomy performed when a part of the gall bladder wall
      was retained for technical reasons. Forty patients underwent partial
      cholecystectomy: for chronic cholecystitis (20), acute cholecystitis (4),
      Mirizzi's syndrome (14), portal hypertension or partially accessible gall bladder
      (one patient each). Four patients (10%) developed infective complications and two
      patients had retained common bile duct stones. In a mean follow up period of 13
      months (range 1-36 mths), only 3 patients have ongoing mild dyspeptic symptoms
      while the rest have remained asymptomatic. Partial cholecystectomy has been found
      to be a safe and effective procedure in difficult cholecystectomy situations,
      since it combines the merits of cholecystectomy and cholecystostomy.

PMID- 8260437
TI  - Lost stone during laparoscopic cholecystectomy: retrieval using a condom.
AB  - Laparoscopic cholecystectomy is becoming increasingly popular for the treatment
      of gall stone disease. In this technique, the gall bladder is dissected free
      under laparoscopic vision and then extracted. We report an interesting
      complication that occurred during extraction of a gall bladder containing a large
      stone and a novel method of overcoming the problem.

PMID- 8260438
TI  - Infected peri-pancreatic necrosis causing gallbladder necrosis by direct
      extension.
AB  - Acute acalculous cholecystitis may develop in patients suffering from necrotizing
      pancreatitis. Conversely, acute pancreatitis may complicate acute gallbladder
      disease. We present a case that lends support to the existence of another
      possibility: gallbladder necrosis caused by direct extension of the necrotizing
      pancreatitic process.

PMID- 8260439
TI  - Adenocarcinoma in Caroli's disease treated by liver transplantation.
AB  - Caroli's disease is characterized by congenital cystic dilatation of the
      intrahepatic bile ducts. In 7% of cases a malignant tumor develops complicating
      the course of the disease. We report the case of a 25 year-old woman in whom
      Caroli's disease was diagnosed at the age of 11. From that time on, she had
      several episodes of cholangitis. In 1989, the abdominal ultrasound and CT scan
      showed dilatation of the intrahepatic bile ducts, intracystic lithiasis and a
      solid mass. FNA cytology showed a papillary adenocarcinoma. At laparotomy a tumor
      was found occupying both hepatic lobes, and intraoperative US showed another two
      nodules in the left lobe. The tumor was considered unresectable. Examination of
      the hilar lymph nodes was tumor-negative. Two weeks later, the patient underwent
      an orthotopic liver transplantation (OLT). The pathological examination confirmed
      Caroli's disease with adenocarcinoma. Two years after OLT, the patient is alive
      with normal liver function and no evidence of disease. To our knowledge this is
      the first case report of adenocarcinoma in Caroli's disease treated by OLT.

PMID- 8260440
TI  - Complications of pancreatic resection reduced by somatostatin.

PMID- 8260441
TI  - Surgery and interventional radiology for benign bile duct strictures.

PMID- 8260442
TI  - Frontal lobe metabolism and cerebral morphology in schizophrenia: 31P MRS and MRI
      studies.
AB  - The relation between frontal lobe membrane phospholipid metabolism as measured by
      31Phosphorus magnetic resonance spectroscopy (31P MRS) and cerebral morphology as
      measured on magnetic resonance images (MRI) was examined in nine first episode
      neuroleptic naive schizophrenic patients. Total corpus callosal area was
      significantly correlated with phosphodiester concentration. When examined
      separately, this relation was confined to the rostral quartile (genu) of the
      corpus callosum. The pathophysiological significance of this finding is discussed
      in relation to neurodevelopmental hypotheses of schizophrenia.

PMID- 8260443
TI  - ERP abnormalities during semantic processing in schizophrenia.
AB  - To examine the neurophysiological and cognitive characteristics of thought
      disturbance in schizophrenic patients, we examined the amplitude, latency, and
      topography of a specific event-related brain potential (ERP), the N400, which is
      elicited by semantically incongruent words and phrases. Twelve chronic
      schizophrenic patients and twelve age-matched control subjects read sentences
      presented visually that had either semantically correct (e.g., 'People pray in
      their local church') or incorrect endings (e.g., 'Every Sunday morning people
      pray in their local nest'). Relative to normal controls, schizophrenic patients
      had significantly reduced N400 amplitude and increased latency to semantically
      anomalous endings. Additionally, a late positive component which follows the N400
      was significantly reduced in amplitude in schizophrenic patients. However,
      patients and controls did not differ significantly in terms of the topographical
      distribution of either the N400 or its late positive potential, examined at 28
      electrode sites. Thus, N400 topography in schizophrenic patients was not
      accompanied by the asymmetry which frequently characterizes the well known
      auditory P300 disturbance in schizophrenic patients. We concluded that these
      findings may reflect a profound disturbance in attentional processes in chronic
      schizophrenia.

PMID- 8260444
TI  - Plasma homovanillic acid and treatment response in a large group of schizophrenic
      patients.
AB  - Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were
      measured in ninety-five Chinese schizophrenic patients free of neuroleptics for
      at least four weeks. These patients were treated with classical antipsychotics
      for six weeks. Pretreatment pHVA was positively correlated with the subsequent
      clinical response (r = 0.408, p < 0.0001). Good responders (BPRS improvement > or
      = 50%, n = 47) had higher pretreatment pHVA levels than poor responders (BPRS
      improvement < 50%, n = 48) (15.7 +/- 8.4 ng/ml versus 9.9 +/- 3.7 ng/ml, p <
      0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a
      more consistent clinical response to the subsequent treatment. Using a pHVA level
      of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA > or
      = 12 responded whereas 65% (31 of 48) who had < 12 did not respond (chi-square =
      13.02, p < 0.0001). These results suggest that higher pretreatment pHVA levels
      may predict a better clinical response to antipsychotics. Based upon the pHVA
      findings, two hypothetical subtypes of schizophrenia are proposed.

PMID- 8260445
TI  - Changes in psychopathology and dyskinesia after neuroleptic withdrawal in a
      double-blind design.
AB  - The goal of this study was to assess the time course of change in psychopathology
      and dyskinesia after neuroleptic withdrawal. Fifteen DSM-III schizophrenic
      patients were abruptly withdrawn in a double-blind fashion from stable
      haloperidol treatment. Weekly ratings of dyskinesia and psychopathology were
      performed for 4 weeks post-withdrawal. There was an overall increase in
      dyskinesia ratings over the 4-week period (p < 0.05) beginning in week 2, with
      dyskinetic movements of the fingers showing the most significant increase (p <
      0.001). There were no overall changes in psychopathology, though the group
      appeared to be bimodal with 6 of the 15 patients showing a significant relapse in
      psychotic symptoms. Neither baseline TD nor psychotic relapse significantly
      interacted with change in TD over time. These schizophrenic patients showed an
      increase in global dyskinesia rating early within four weeks of neuroleptic
      withdrawal. This time course did not appear to be associated with reemergence of
      psychopathology which occurred later. A significant minority of patients relapsed
      within this time period. This suggests the relative safety of brief periods of
      neuroleptic withdrawal for carefully selected patients in a controlled setting
      with specific goals (e.g., for evaluation or in preparation for clozapine) and
      the need to further understand who is at risk for rapid relapse.

PMID- 8260446
TI  - Clinical, psychological and neuroradiological findings in a case of chronic
      schizophrenia with cognitive impairment and a mis-sense mutation at codon 713 of
      the beta amyloid precursor protein gene.

PMID- 8260447
TI  - Positive and negative symptoms in the psychoses: multidimensional scaling of SAPS
      and SANS items.

PMID- 8260448
TI  - Editor's comments on Galdos et al. (1993)

PMID- 8260449
TI  - Constitutive expression of transgenic heat stable antigen (mCD24) in lymphocytes
      can augment a secondary antibody response.
AB  - The murine heat stable antigen (HSA, mouse CD24) is a glycosyl
      phosphatidylinositol-anchored cell surface protein which is primarily expressed
      in immature but not mature cells of several hematopoietic lineages and in
      neuronal tissue. The function of HSA is not known but there is evidence in
      lymphocytes that it is involved in cell adhesion and in cell activation. We
      examined the effect of constitutive HSA expression on the maturation and on the
      function of B and T cells in transgenic mice. Transgenic HSA was strongly
      expressed throughout all stages of T cell maturation without changes in absolute
      cell number or proportions of subpopulations both in the thymus and in the
      periphery. The size of the B cell compartment was also unchanged. Thus, we
      conclude that in the T lineage the loss of HSA expression is not mandatory for
      maturation. On the functional level, two parameters of immune function were
      measured. When the ability to activate peripheral T cells expressing transgenic
      HSA was tested in a mixed lymphocyte reaction, no significant difference in the
      stimulation index and cytolytic activity was detected between transgenics and
      control littermates. However, when immunized with a T cell dependent antigen,
      transgenic mice showed 10-fold higher serum IgG1 titers. This suggests that the
      expression of transgenic HSA in cells normally negative for HSA (e.g. peripheral
      T cells or memory B cells) leads to a better stimulation of lymphocytes during a
      secondary antibody response.

PMID- 8260450
TI  - Mechanisms that limit the diversity of antibody: three sequentially acting
      mechanisms that favor the spontaneous production of germline encoded anti
      phosphatidyl choline.
AB  - Antibody to phosphatidyl choline (PtC) is produced spontaneously in mice, by
      approximately 2-10% of naturally occurring CD5+ (B1) B cells in the peritoneum.
      Much of this antibody is encoded by the VH11 gene associated with a specific V
      kappa 9 gene. Constraints on the size and structure of the H chain CDR3 have been
      defined from nucleotide sequences of genes expressed by hybridomas and lymphomas
      derived from adult mice. All employ JH1 and all encode tyrosine as the first
      amino acid in CDR3, which is either nine or 10 amino acids long; the last six are
      always the same, start with tyrosine, and are rich in aromatic amino acids. Those
      with nine amino acids in CDR3 have glycine or serine in the second position and
      asparagine, serine or proline in the third; those with 10 have an additional
      aspartate or glycine inserted after the first tyrosine. DSP2 genes are used by
      80% and DFL16 by 20%. Productively rearranged VH11 genes in neonates and in 18
      day fetal liver display a greater, but still limited degree of diversity. All
      four JH genes are used and the length of CDR3 varies from three to 12 amino
      acids, but the first is tyrosine in 58 of 61 and DSP2 genes are used by 80% of
      these productive VDJ assemblies. Non-productive rearrangements of VH11 in fetal
      liver show a different pattern; 41% use DFL16 genes and only 40% have a TAx codon
      in the first position of CDR3. All rearrangements show evidence of a bias in
      favor of joining the VH11 gene to D genes at positions of matching nucleotide
      overlap.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260451
TI  - T cell anergy is programmed early after exposure to bacterial superantigen in
      vivo.
AB  - We have investigated the effects of the protein synthesis inhibitor,
      cycloheximide (CHX), on the induction of post-thymic T cell tolerance in mice
      primed with the bacterial superantigen, Staphylococcus aureus enterotoxin B
      (SEB). A single injection of 1 mg CHX prevented protein synthesis in splenic
      cells for < 6 h in vivo. The concomitant administration of SEB and CHX prevented
      induction of SEB-specific anergy, but did not interfere with the deletion of SEB
      specific V beta 8+ T cells by activation-induced, programmed cell death. When CHX
      was given > or = 24 h after SEB administration the expression of anergy was not
      affected. These findings suggest that anergy and deletion represent independent
      processes. Furthermore, these observations, together with the fact that SEB
      retains the potential to induce anergy in specific T cells 8 h after priming in
      vivo, imply that the determination of alternate fates (anergy or death) occurs at
      early time points after SEB injection.

PMID- 8260452
TI  - Induction of IFN-gamma in macrophages by lipopolysaccharide.
AB  - In this paper we report that macrophages can be stimulated to express detectable
      levels of IFN-gamma-specific mRNA. Macrophages from lipopolysaccharide (LPS)
      responsive, C3H/OuJ mice are induced by LPS to increase steady-state levels of
      IFN-gamma-specific mRNA, while those from LPS-hyporesponsive C3H/HeJ mice are
      not. This interstrain variation is apparently the result of LPS-specific signal
      differences since macrophages derived from both Lpsn and Lpsd mouse strains are
      able to produce comparable levels of IFN-gamma-specific mRNA following
      stimulation with polyinosinic-polycytidylic acid. The identity of the cell type
      responsible for this IFN-gamma message appears to be the macrophage as IFN-gamma
      specific mRNA was also detectable following T and natural killer cell depletion,
      in the LPS-stimulated RAW 264.7 cell line, and in a homogeneous population of
      mature macrophages propagated in vitro by stimulation of bone marrow progenitors
      with recombinant colony stimulating factor-1. Immunofluorescent staining of fixed
      and permeabilized LPS-stimulated macrophages confirmed the presence of
      immunoreactive IFN-gamma protein. The possible significance of IFN-gamma
      production by macrophages is discussed in the context of normal macrophage
      differentiation as well as the inflammatory immune response.

PMID- 8260453
TI  - Distinct intracytoplasmic sequences are required for endocytosis and phagocytosis
      via murine Fc gamma RII in mast cells.
AB  - In the present work, we studied the phagocytic and endocytic properties of murine
      Fc gamma RII in mast cells. Mouse mast cells express high-affinity receptors for
      monomeric IgE and three low-affinity receptors for complexed IgG: Fc gamma RIIb1,
      Fc gamma RIIb2, and Fc gamma RIII. In previous studies we showed that, when
      aggregated by multivalent ligands, murine Fc gamma RIII, but not Fc gamma RII,
      triggers the release of inflammatory mediators and cytokines by mast cells. Upon
      Fc gamma R aggregation, mast cells not only release intracellular materials, they
      also internalize particulate and soluble immune complexes. We compared the
      ability of the two Fc gamma RII isoforms to trigger phagocytosis and endocytosis
      in RBL-2H3 cells stably transfected with cDNAs encoding wild-type, deleted, and
      tyrosine mutant Fc gamma RIIb1 or Fc gamma RIIb2. We found that Fc gamma RIIb2,
      but not Fc gamma RIIb1, triggered both phagocytosis and endocytosis. We
      identified distinct intracytoplasmic sequences necessary for Fc gamma RIIb2
      mediated endocytosis and phagocytosis respectively, and we observed that two
      tyrosine residues, located in each of these sequences, are critical for
      endocytosis and/or phagocytosis. Our data indicate that the two internalization
      pathways diverge as early as signal transduction.

PMID- 8260454
TI  - TCR isoform containing the Fc receptor gamma chain exhibits structural and
      functional differences from isoform containing CD3 zeta.
AB  - The structure and function of the TCR-CD3 complex containing a homodimer of the
      gamma chain of the high affinity receptor for IgE (FcR gamma) (FcR gamma+ TCR)
      was investigated by transfecting the FcR gamma gene into a CD3 zeta-, CD3 eta-,
      FcR gamma- T cell line. Introduction of FcR gamma, as well as CD3 zeta, induced a
      high expression of the TCR-CD3 complex on the cell surface. Transfected FcR gamma
      formed a homodimer and associated firmly with the TCR alpha beta dimer but only
      weakly with the CD3 gamma delta epsilon. Stimulation of both FcR gamma and CD3
      zeta transfectants by antibodies against TCR or CD3 induced accumulation of
      inositol phosphates, the Ca2+ response, IL-2 production, and growth inhibition.
      On the other hand, antigen stimulation of transfectants expressing FcR gamma as
      well as CD3 zeta induced IL-2 production, but only the latter exhibited the
      antigen-induced growth inhibition. In vitro kinase assay suggested that the CD3
      zeta dimer but not the FcR gamma dimer associates with the Fyn kinase. These
      results indicate that the FcR gamma homodimer is able to form a functional TCR
      complex but that the mode of assembly and the signaling function of FcR gamma+
      TCR, including its association with tyrosine kinase(s), may differ from the TCR
      CD3 complex containing CD3 zeta homodimers (zeta+ TCR). This provides an example
      which illustrates that different TCR isoforms mediate distinct signals and
      functions.

PMID- 8260455
TI  - Cytotoxic T cells from a human chimera induce regression of Epstein-Barr virus
      infected allogeneic host cells.
AB  - The anti-Epstein-Barr virus (EBV) T cell response was studied in a severe
      combined immunodeficiency patient (PS) in whom stable peripheral blood chimerism
      was induced by transplantation of fetal liver stem cells from two donors. PS is
      characterized by a complete mismatch between the T lymphocytes, derived from the
      transplants, and all the other cells, including EBV+ B lymphocytes, of host
      origin. The patient's peripheral blood mononuclear cells were incubated with EBV
      and cultured for 1 month. In these cultures, T lymphocytes strongly inhibited the
      proliferation of the host EBV-infected lymphoblastoid cell line (PS-LCL) and,
      after expansion under repeated stimulation with PS-LCL in the presence of IL-2,
      they specifically inhibited the growth of host-HLA-matched LCL. In contrast,
      these T lymphocytes failed to recognize and to lyse EBV-infected HLA-identical
      targets. Lysis of PS-LCL was reduced after incubation with W6/32 or with anti-DR
      antibodies, suggesting a role for host HLA class I and HLA class II determinants
      in the lysis of the target cells. PS-HLA class I and HLA class II-matched LCL
      were also killed. However, lymphocytes from the father or from the mother were
      not killed when not EBV-infected, indicating that host HLA antigens served as
      restricting determinants for the anti-viral T cells.

PMID- 8260456
TI  - Extracellular matrix components of the mouse thymic microenvironment. III. Thymic
      epithelial cells express the VLA6 complex that is involved in laminin-mediated
      interactions with thymocytes.
AB  - We describe herein the expression of the VLA6 complex by murine thymic epithelial
      cells (TEC). The immunohistochemical distribution revealed that VLA6 is found in
      both thymic medullary and subcapsullary areas. Moreover, studies by
      immunoelectron microscopy revealed a membrane labeling of the VLA6 molecule,
      including at desmosomal sites. By means of immunoblotting, immunoprecipitation,
      and affinity chromatography of extracts from a mouse TEC line, we further
      demonstrated that VLA6 is a laminin (LN) receptor in these cells. In keeping with
      this finding, we showed that TEC adhesion, spreading, and proliferation were
      enhanced in vitro by LN. The fact that VLA6 is also expressed by the large
      majority of thymocytes raised the hypothesis that it might be involved in LN
      mediated TEC-thymocyte interactions. Interestingly, in vitro experiments showed
      that there is an increase in the TEC-thymocyte adhesion upon glucocorticoid
      hormone treatment, a situation in which the expression of VLA6 as well as LN is
      enhanced. Most importantly, this adhesion can be reversed by pre-treating TEC
      with an anti-alpha 6 integrin mAb. Additionally, spontaneous in vitro thymocyte
      release by thymic nurse cell complexes was enhanced by LN and partially blocked
      by anti-alpha 6 or anti-beta 1 antibodies. Our results suggest that VLA6 is
      involved in LN-mediated TEC-thymocyte interactions that can be relevant for
      thymic microenvironmental cell physiology and intrathymic T cell differentiation
      events.

PMID- 8260457
TI  - Immunization with live versus killed Salmonella typhimurium leads to the
      generation of an IFN-gamma-dominant versus an IL-4-dominant immune response.
AB  - The mechanisms responsible for differential commitment of effector T cells to the
      production of either the IL-4/5/10 group or to the IL-2/IFN-gamma group of
      lymphokines during an immune response have not yet been clearly elucidated. We
      have used Salmonella typhimurium as a model murine bacterial parasite in BALB/c
      mice for live-cell versus killed-cell immunization and looked at the immune
      response in terms of delayed type hypersensitivity (DTH), IgG subclass
      distribution in the serum antibody response, and antigen-specific T cell
      proliferation and lymphokine secretion. The results indicate that the two forms
      of immunogen induce qualitatively different immune responses. Intraperitoneal
      immunization with live bacteria induces an IFN-gamma-dominant immune response
      associated with a strong DTH reaction and relatively higher levels of specific
      antibodies belonging to the IFN-gamma-dependent IgG2a isotype rather than the IL
      4-dependent IgG1 isotype. Immunization with heat-killed bacteria gives rise to an
      IL-4-dominated response that shows excellent proliferative capacities in vitro,
      with lower levels of DTH responses and comparatively high levels of specific
      antibodies of the IgG1 isotype. IL-2 production in the responses generated by the
      two modes of immunization, however, is not preferentially associated with IFN
      gamma production, unlike the reported profiles of long-lived murine T cell clones
      in vitro.

PMID- 8260458
TI  - Function of alpha beta TCR+ intestinal intraepithelial lymphocytes: Th1- and Th2
      type cytokine production by CD4+CD8- and CD4+CD8+ T cells for helper activity.
AB  - The immunobiological function of lymphocytes within the epithelium (IELs) of the
      small intestine is incompletely understood; however, it has been shown that
      intestinal IEL T cells exhibit cytotoxicity, produce cytokines, and perform some
      regulatory roles. In this study, we have focused on CD4+, alpha beta TCR+ IELs,
      which comprise approximately 15-20% of the total population, for helper
      functions. We have assessed the profile of type 1 or type 2 Th cell cytokines
      produced in alpha beta TCR bearing CD4+CD8- and CD4+CD8+ (double positive, DP)
      intestinal IELs by cytokine-specific ELISPOT and by reverse transcription
      polymerase chain reaction. Help for B cells taken from Peyer's patches (PP)
      allowed us to assess IEL function for mucosal antibody responses. Freshly
      isolated CD4+CD8- IEL T cells contain Th2-type cells, e.g. high numbers of IL-5
      secreting (spot forming) cells (SFC) followed by IL-4 and IL-6, while DP T cells
      have IL-5 and IL-6 producing cells, but not IL-4. In addition to Th2-like
      cytokine producing T cells, both CD4+ T cell subsets contain IFN-gamma secreting
      Th1-type cells but neither subset synthesizes IL-2. Stimulation of CD4+CD8- and
      DP T cells with solid phase mAb anti-CD3 resulted in production of IL-2 in
      addition to IFN-gamma, IL-5, and IL-6, and this treatment stimulated DP T cells
      to produce IL-4. When freshly isolated intestinal IEL T cells were separated into
      CD4+ and CD4- cells, and co-cultured with PP B cells, the former subset supported
      Ig synthesis including IgA responses, while the later fraction did not.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260459
TI  - Factors influencing the susceptibility to gingivitis during childhood--a review.
AB  - A variety of biological changes take place during childhood which have an impact
      on the development of gingival inflammatory disease. This paper reviews the
      literature concerning changes in the susceptibility to gingivitis during
      childhood. It is concluded that during certain periods the risk of developing
      gingivitis is relatively low, while in others the gingival tissues are more
      susceptible and react to bacterial irritation with inflammation. Factors that may
      be responsible for these changes include differences in bacterial plaque
      composition, in immune defence systems and in morphology of the gingival tissues,
      and also factors related to tooth eruption and puberty.

PMID- 8260460
TI  - A treatment need index: a pilot study.
AB  - The traditional caries index, DMF, provides inadequate information to assess
      dental treatment needs of a community. Dental health planners are often called
      upon to estimate the treatment needs, costs, time and personnel required for a
      proposed programme. A treatment needs index (TNI) is presented which provides
      important data for dental health planning. The index defines seven basic levels
      of treatment: (0) no treatment needed; (1) preventive treatment; (2) fissure
      sealants; (3) initial conservative restorations; (4) moderate conservative
      restorations; (5) advanced conservative restorations; and (6) radical treatment,
      including pulp therapy, prosthetic restorations and extractions. A pilot study
      and an example comparing data of both DMF and TNI demonstrates the values of the
      latter index. The Treatment Needs Index provides a more accurate description of
      caries severity and extent than does the traditional DMF index, and can be used
      to estimate the time required to treat a community.

PMID- 8260461
TI  - The prevalence of dental caries and gingivitis and their relationship to social
      class amongst nursery-school children in Nairobi, Kenya.
AB  - Four hundred and forty-six children attending nursery schools in Nairobi were
      examined for caries and gingivitis. Assessment of social class was based on the
      occupation of the head of the child's household. Amongst 3-year-old children, 62%
      were caries-free and the mean dmft was 1.35. Amongst 5-year-olds 50% were caries
      free and the mean dmft was 1.88. Thirty-seven per cent of the children had
      evidence of gingivitis, with the proportion changing little with age. There was
      no evidence of either caries or gingivitis being significantly related to social
      class, although children in the higher classes had more filled teeth.

PMID- 8260462
TI  - Congenital aplasia of major salivary glands in a 4-year-old child.
AB  - The case of a 4-year-old girl with marked xerostomia and rampant caries is
      described. Investigation revealed complete aplasia of all four major salivary
      glands, which is extremely rare. Eleven primary teeth were extracted and a strict
      caries-preventive regime introduced. The patient had previously been advised to
      suck citrus-flavoured sweets to stimulate saliva flow, but this must be
      discouraged.

PMID- 8260463
TI  - Condylar hyperplasia causing progressive facial asymmetry during orthodontic
      treatment--a case report.
AB  - Condylar hyperplasia is defined and its aetiology and prevalence are briefly
      reviewed. A case is presented to illustrate how the progressive nature of the
      condition can create problems for the clinician, particularly during orthodontic
      treatment of a child or adolescent patient. The benefits of interceptive surgery
      are illustrated, although such an approach does not necessarily mean that further
      surgery is avoided at the completion of growth.

PMID- 8260464
TI  - Osteopathia striata--a case report.
AB  - Osteopathia striata is an unusual skeletal condition that can affect the bones of
      the skull quite markedly and result in dental problems that have rarely been
      discussed in the literature. The characteristic features exhibited by the patient
      in this case report were dense maxillary and mandibular bone, a high forehead
      with frontal bossing, a broad nasal bridge, prominent zygomatic arches and
      thickened angles of the mandible. The mouth opening was limited as a result of
      sclerosis of the mastoid process, and right lateral excursion of the mandible was
      reduced, probably because of a deformity of the left condyle.

PMID- 8260465
TI  - Factors affecting the availability of sugar-free medicines for children--a survey
      in the UK.
AB  - Because use of sugar-containing paediatric medicines is an aetiological factor in
      dental caries, sugar-free alternatives are slowly becoming more readily
      available. However, it is claimed that, for a variety of reasons, their
      production is difficult. This investigation was undertaken to determine whether
      problems exist in the formulation, production and availability of sugar-free
      medicines. A structured questionnaire was used with personnel involved in the
      production, marketing and wholesaling of paediatric medicines in the UK.
      Information was obtained from interviews with, or from questionnaires completed
      by, personnel of five pharmaceutical and five wholesale companies. The findings
      indicated that the only obstacle to producing sugar-free medicines is slightly
      higher cost, and that manufacturers are influenced to change mainly by consumer
      pressure. It was concluded that the dental profession should advise the public to
      demand sugar-free medicines and doctors to prescribe them.

PMID- 8260466
TI  - Examination of energy utilization in cattle offered a forage diet at near- and
      sub-maintenance levels of feeding.
AB  - Eight Friesian calves were reared from birth to the start of the experiment at a
      predetermined growth rate of 1.0 kg/d. Four calves (group 1) commenced the
      experiment at 22 weeks of age and the remainder (group 2) at 34 weeks, and feed
      intake was calculated to provide sufficient metabolizable energy to sustain zero
      energy balance (Em). Between experimental days 30 and 56 at maintenance levels of
      feeding, respiratory exchange measurements were made using open-circuit
      calorimetry to provide indirect estimates of heat production (H) simultaneous
      with measurements of faecal and urinary excretion of energy and N. A datum point
      for Em and H was established for each animal giving mean values for Em of 491 and
      537 and for H of 476 and 511 kJ/kg live weight (LW)0.75 per d for groups 1 and 2
      respectively. Treatment levels calculated as 0.25, 0.5, 0.75 and 1.25 of dry
      matter intake required to sustain the measured Em, were imposed on individual
      animals after day 56 and further measurements of H and faecal/urinary balance
      were made between days 72 and 84 followed by measurements of fasting heat
      production (FHP) during days 86-90 from the two animals in each group which had
      received the 0.75 and 1.25 levels of intake. Regression analysis of the treatment
      levels indicated separate linear models which predicted Em at 419 and 473 kJ/kg
      LW0.75 per d for groups 1 and 2 respectively. The incorporation of FHP with
      partitioning of faecal and urinary energy losses measured during fasting altered
      the relationship but not the predicted Em. Overall predicted Em (days 72-84) from
      all models were 406 and 478 kJ/kg LW0.75 per d for groups 1 and 2 respectively
      which were significantly lower (P < 0.05) than Em measured during days 30-56.

PMID- 8260467
TI  - No major differences in energy metabolism between matched and unmatched groups of
      'large-eating' and 'small-eating' men.
AB  - Rates of energy expenditure (J/kg fat-free mass (FFM) per min) in normal weight,
      'small-eating' men were compared with those obtained for normal weight (n 8) and
      underweight (n 5) 'large-eating' men. For the matched groups of 'large-' and
      'small-eaters' there were no differences in resting metabolic rate (RMR)
      measurements but during controlled daily activities there was a small but
      significant increase (P < 0.05) in energy expenditure in the 'large-eaters'.
      These results contrast with those obtained for the unmatched groups where energy
      requirements were about 10% (P < 0.01) higher in the underweight 'large-eaters'
      at rest but were not different during the more energetic (walking) activities.
      However, after adjustment for differences in FFM between these two groups, the
      resting energy expenditures of the 'large-eaters' (82.54 (SE 1.51) J/kg FFM per
      min) were similar to those of the 'small-eaters' (81.87 (SE 1.51) J/kg FFM per
      min). Oral temperatures were significantly higher in the matched (0.35-0.65
      degrees) and unmatched (0.7-0.9 degrees) 'large-eaters' both at rest and during
      the different activities, but the thermic effect of food (50 kJ/kg FFM) was one
      fifth lower (not significant) in both groups of 'large-eaters'. These results
      provide little evidence for any major metabolic differences between groups of
      'large-eating' and 'small-eating' men.

PMID- 8260468
TI  - Metabolic utilization of dietary energy and nutrients for maintenance energy
      requirements in sows: basis for a net energy system.
AB  - Digestible energy (DE), metabolizable energy (ME) and net energy for maintenance
      (NEm) values of a set of fourteen diets were measured in six adult sows fed at
      and below their maintenance energy level. The efficiency of ME for NEm was
      estimated from heat production (HP) measurements (indirect calorimetry) at these
      different feeding levels. HP was partitioned between HP due to physical activity,
      thermic effect of food (TEF) and fasting heat production (FHP). The amounts of DE
      digested in the small intestine or in the hindgut were measured. Equations for
      prediction of NEm from dietary characteristics were calculated. HP at maintenance
      level averaged 400 kJ/kg body-weight0.75, 16 and 19% of the total being due to
      physical activity and TEF respectively. The efficiency of ME for NEm averaged
      77.4% with higher values for digestible diethyl ether extract (100%) and
      starch+sugar (82%). The efficiencies of digestible crude protein (N x 6.25) and
      digestible residue averaged 69 and 56% respectively. The energy absorbed from the
      small intestine was used more efficiently than the energy fermented in the
      hindgut (82 v. 59%). These values are comparable with those obtained in growing
      pigs. The NEm content of diets can be predicted accurately from equations
      including DE (or ME) values and some dietary chemical characteristics.

PMID- 8260469
TI  - Adaptive changes in energy expenditure during mild and severe feed restriction in
      the rat.
AB  - Using a new-generation open-circuit calorimeter capable of monitoring the cost of
      activity, and thereby both the real thermic effect of feeding (TEF) and basal
      metabolism in free-moving freely-feeding rats, we have reassessed the proposal
      that when food intake is restricted an adaptative reduction in energy expenditure
      participates in the achievement of energy balance. Total energy expenditure,
      energy expenditure due to spontaneous activity, TEF, basal energy expenditure and
      respiratory quotient (RQ) were computed by indirect calorimetry in rats given
      either a mildly restricted (MR) feed intake for 20-30 d (17 g feed/d) or a
      severely restricted (SR) feed intake for 1-10 d (4 g feed/d). In MR rats no
      significant changes in any of the measured variables were observed. In contrast,
      SR rats exhibited an adaptative reduction in energy expenditure due to a reduced
      spontaneous activity and probably also due to a reduced basal energy expenditure.
      On the other hand none of the animals fed on a restricted feed intake showed an
      adaptative TEF decrease, suggesting that TEF under ad lib. feeding is rather an
      obligatory process that does not include an adaptative component. Taken together,
      these results point out that under restricted feeding most of the decrease in
      energy expenditure is associated with simple passive mechanisms, such as body
      weight loss, and with the reduced feed intake per se. Only under severe feed
      restriction can some additional energetic economy be obtained from a possible
      reduction of basal metabolism, and to some extent from reduced activity.

PMID- 8260470
TI  - In vivo total body water assessment by total body electrical conductivity in rats
      suffering perturbations of water compartment equilibrium.
AB  - Total body electrical conductivity (TOBEC) is a simple and non-invasive method
      for the assessment of body composition in vivo. Information regarding the
      applicability of TOBEC in the condition of abnormal fluid balance is scarce. In
      the present paper we give the results of the comparison between TOBEC and total
      body water (TBW; assessed by the tritium dilution technique) in three groups of
      animals: (1) healthy (n 17), (2) expanded fluid volume by secondary biliary
      cirrhosis (SBC; n 9) and (3) Furosemide-treated rats (n 9). The TOBEC score and
      TBW by tritium dilution were found to be highly correlated in the pooled sample
      (r 0.90) and in normal (r 0.87), SBC (r 0.73) and Furosemide-treated (r 0.89)
      rats. However, the relationship between TOBEC and TBW, described by least-squares
      regression analysis, was found to be similar for SBC and normal rats but was
      significantly different for Furosemide-treated and normal rats. These findings
      suggest that TOBEC is unable to track TBW accurately when the ratio between
      intracellular and extracellular water is chronically or acutely altered.

PMID- 8260471
TI  - Protein requirement of young adult Nigerian females on habitual Nigerian diet at
      the usual level of energy intake.
AB  - A short-term N balance study was conducted in twelve healthy female adults aged
      21-32 years to determine their protein requirement. Four dietary protein levels
      (0.3, 0.4, 0.5 and 0.6 g protein/kg per d) were used. Energy intake of the
      subjects was kept constant at 0.18 MJ/kg per d. All subjects maintained their
      normal activity throughout the study period. N excretion was determined from the
      measurements of N in a total collection of urine, faeces, sweat and menstrual
      fluid for each dietary period. N balance during the four protein levels were 
      15.15 (SD 5.95), -5.53 (SD 6.71), +6.15 (SD 4.76) and +12.05 (SD 8.63) mg N/kg
      per d for 0.3, 0.4, 0.5 and 0.6 g protein/kg per d respectively. The calculated
      average N requirements from regression analysis was 76.0 (SD 3.37) mg N/kg per d
      (0.48 g protein/kg per d). The estimate of allowance for individual variation to
      cover the 97.5% population was 95 mg N/kg per d (0.6 g protein/kg per d). The net
      protein utilization (NPU) of the diet was 0.55. When compared with a similar
      study with men, there was a significant difference in the protein requirement
      between sexes. Thus, the unjustifiable sex difference in the protein allowance
      recommended by the Food and Agriculture Organization/World Health
      Organization/United Nations University (1985) Expert Consultation group must be
      reviewed.

PMID- 8260472
TI  - A metabolic nitrogen balance study for 40 d and evaluation of the menstrual cycle
      on protein requirement in young Nigerian women.
AB  - A long-term N balance study was carried out to determine the adequacy of an
      estimated protein requirement level recommended for young healthy Nigerian women
      and the effect of the menstrual cycle on the requirement. Eleven healthy young
      women, 25 (SD 2.6) years, were fed on a diet providing 0.6 g protein (N x
      6.25)/kg per d and an average energy intake of 0.17 (SD 0.012) MJ/kg per d.
      Urine, faeces, sweat and menstrual fluids were collected for estimation of N
      balance. Menstrual N loss varied among individuals ranging from 46 to 124 mg N/d
      with an average of 89 (SD 21.8) mg N/d. Individual N balance was found to vary
      according to the day of the menstrual cycle. Positive N balances were recorded at
      about ovulation while negative balances were observed just before the onset of
      menstruation. The average N balance ranged from +8.49 (SD 5.64) to -430 (SD 7.84)
      mg N/kg per d. Nevertheless, an overall cumulative positive N balance of +5.7 (SD
      6.98) mg N/kg per d which did not change significantly with time was observed for
      the last 5 d of two consecutive 20 d diet periods, although three subjects were
      in negative N balance. Blood biochemical measurements were stable except for one
      subject who had elevated serum aspartate aminotransferase (EC 2.6.1.1) levels.
      These findings suggest that our estimate of protein requirements was sufficient
      to achieve N balance equilibrium in a majority (70%) of young women. However, to
      satisfy 97.5% of the population, slight adjustments might be necessary in the
      energy intake since subjects who were in cumulative negative N balance also lost
      weight.

PMID- 8260473
TI  - Tissue- and substrate-dependent responses of oxidative phosphorylation to dietary
      protein level in chicks.
AB  - The ADP:O values in both cardiac and hepatic mitochondria have significantly
      decreased with an increase in protein level after 7, 14 and 21 d of feeding
      (Toyomizu et al. 1992). The present studies were undertaken to clarify tissue
      specific effects of dietary protein levels on oxidative phosphorylation in the
      liver, kidney, skeletal muscles and small intestine and to characterize oxidative
      metabolism with diverse substrates in the liver. Chicks were fed on semi-purified
      diets of different protein levels (7, 25, 43 and 61% of metabolizable energy
      content) for 21 d. The responses of protein levels to oxidative phosphorylation
      showed tissue-dependency; although liver mitochondria of chickens fed on higher
      protein diets exhibited reduced ADP:O values and state 3, neither changes in
      ADP:O value nor state 3 and state 4 rates were observed in the isolated
      mitochondria from kidney and skeletal muscles. Small intestinal mucosal
      mitochondria from chickens fed on a high (61%)-protein-energy diet showed
      significantly reduced ADP:O value and respiratory control ratio when compared
      with medium-protein-energy diets (25 and 43%). In liver mitochondria showing the
      most sensitive dependency to the levels of dietary protein, the ADP:O value
      decreased with increasing protein levels when pyruvate+malate- or glutamate
      requiring complexes I, III and IV of the electron transport chain were used as
      substrates, but it did not change when succinate-requiring complexes II, III and
      IV or ascorbate+tetramethyl-p-phenylenediamine requiring complex IV was used.
      These results imply that impaired oxidative phosphorylation capacities with
      increasing dietary protein levels may be associated with functional damage to the
      respiratory chain for electron flow from NAD-linked substrates to the ubiquinone
      pool.

PMID- 8260474
TI  - An integrated, dynamic model of feed hydration and digestion, and subsequent
      bacterial mass accumulation in the rumen.
AB  - Hydration of feeds and bacterial attachment to feed particles are thought to play
      major roles in rumen digestion of fibrous feedstuffs. The objective of the
      present study was to integrate these phenomena in a mechanistic model that could
      be used for data analysis. The proposed model was based on the conversion of
      biomass, where digestion end-products can be used for the synthesis of bacterial
      mass. Digestion of the potentially digestible fraction and subsequent
      accumulation of bacterial mass was based on a sequential, three-compartment
      model. These compartments represented substrate undergoing hydration, digestion,
      and bacterial mass accumulation. A fraction of the substrate was used for
      synthesis of bacterial mass. It was assumed that these bacteria associate either
      temporarily or permanently with the remaining substrate. Dacron bags containing
      either dry or fully-hydrated lucerne (Medicago sativa), maize (Zea mays) cobs,
      orchard grass (Dactylis glomerata), and wheat straw were incubated in the rumen
      of a steer that was infused continuously with (15NH4)2SO4. The 15N-enrichments of
      isolated particle-associated bacteria and residue remaining in the bags were used
      to estimate bacterial attachment. Substrate remaining and microbial mass
      accumulation were analysed simultaneously. Hydration did not appear to limit
      digestion. Fractional rate of digestion and appearance of attached bacterial mass
      was fastest for lucerne. For lucerne, 5% of the digestion end-products were used
      for synthesis of bacteria that associated with the substrate, whereas for maize
      cobs, orchard grass, and wheat straw this was 16, 14, and 19% respectively. Less
      than 2% of digestion end-products were used for synthesis of bacteria that
      permanently remained associated with the substrate. Permanent association can
      occur only with the indigestible fraction, and probably represents bacterial
      debris. Lysis and/or detachment of bacterial cells was highest for lucerne, and
      was indicative of the rapid dynamics of lucerne digestion.

PMID- 8260475
TI  - In vitro digestibility of different prey species of minke whales (Balaenoptera
      acutorostrata).
AB  - Information on diet composition, daily energy expenditure, energy storage and the
      utilization of energy in the prey are important factors when evaluating the food
      consumption of minke whales (Balaenoptera acutorostrata) during their summer stay
      in northern waters. The purpose of the present study was in this context to
      obtain information on the digestible energy (DE) of different prey selected by
      minke whales. An in vitro three-stage digestion technique, simulating the
      different compartments of the digestive system, has been developed. The initial
      step simulated the anaerobic microbial fermentation of substrate in the
      forestomach. The next stage included the addition of pepsin (EC 3.4.23.1)-HCl,
      simulating ventricle enzymic decomposition, and finally, in the third step, fresh
      extract from duodenal contents was used to simulate enzymic intestinal
      degradation of the remaining components of the food. The inoculum was normally
      obtained from animals which had recently eaten the prey to be tested. In such
      tests we obtained a dry matter disappearance (DMD) and a DE for herring (Clupea
      harengus) of 80.4 (SD 5.0)% (n 18) and 92.1 (SD 3.7)% (n 16) respectively, and a
      DMD of krill (Thysanoessa sp.) of 83.4 (SD 4.9)% (n 6). The DMD of krill was
      reduced to 73.8 (SD 7.3)% (n 8) while the DE was 70.6 (SD 10.4)% (n 7) when
      inoculum from whales which had recently eaten cod (Gadus morhua) and haddock
      (Melanogrammus aeglefinus) was used. These results indicate a high digestibility
      of the most common species of prey in these animals, and also that the whales
      have little difficulty in changing from one prey species to another.

PMID- 8260476
TI  - The effect of non-starch polysaccharide supplementation on circulating bile
      acids, hormone and metabolite levels following a fat meal in human subjects.
AB  - The effects of guar gum, sugar-beet fibre (SBF) and wheat bran supplementation of
      a high-fat test meal were compared with an NSP-free control meal and a meal
      containing an equivalent amount of the ion-exchange resin cholestyramine in
      healthy non-obese human volunteers. Their effects on gastric emptying,
      postprandial circulating bile acids, triacylglycerols and gastrointestinal
      hormone levels were studied. The in vitro binding of NSP and cholestyramine to [1
      14C]glycocholic acid was measured and compared with their in vivo effect. Guar
      gum and cholestyramine supplementation significantly lowered circulating
      postprandial bile acid, triacylglycerol and gastric inhibitory polypeptide
      concentrations, but sugar-beet fibre and wheat bran were without effect. Liquid
      gastric emptying, as assessed by circulating paracetamol levels, was slightly
      accelerated in the guar gum-supplemented meal. Glycocholic acid bound strongly to
      the insoluble fraction of cholestyramine and the soluble fraction of guar gum.
      The insoluble fractions of SBF and wheat bran bound only small quantities of
      glycocholate; no bile acid binding was detected in the soluble fractions of these
      NSP. The study demonstrates that measurement of postprandial bile acids enables
      an indirect measurement to be made of bile acid binding to NSP in vivo. The
      results support the hypothesis that the hypocholesterolaemic action of guar gum
      is largely mediated via interruption of the enterohepatic bile acid circulation,
      but indicate that the hypocholesterolaemic action of SBF is mediated by another
      mechanism.

PMID- 8260477
TI  - Plasma lipids and large bowel volatile fatty acids in pigs fed on white rice,
      brown rice and rice bran.
AB  - Adult male pigs were fed on a diet containing (% of energy) fat 25 starch 55 from
      white rice and providing 20 g fibre/pig d (diet WR). In two other groups rice
      bran was added to the diet to provide 43 g fibre/d. One group received the diet
      unmodified (diet RB), but in another (diet RO) heat-stabilized unrefined rice oil
      replaced the palm oil. In a further group brown rice replaced white rice and
      provided 37 g fibre/pig per d (diet BR). Plasma cholesterol concentrations were
      similar with diets WR, RB and BR. With diet RO the concentration was
      significantly lower than with diets WR and BR but was not different from diet RB.
      Plasma high-density-lipoprotein-cholesterol and plasma triacylglycerols were
      unaffected by diet. In all groups, digesta mass rose from the caecum to the
      proximal colon but fell in the distal colon. Diet WR gave the lowest digesta mass
      while diet BR gave a significantly higher mass along the large bowel length. RB-
      and RO-fed pigs had equal masses of digesta which were intermediate between BR-
      and WR-fed pigs at all sampling sites. Pools of individual and total volatile
      fatty acids (VFA) in the proximal large bowel were unaffected by diet. Pools of
      total and individual VFA in the median and distal colon were lowest with diets WR
      and RB and significantly higher with diet BR. In these regions of the colon pools
      of acetate in RO-fed pigs did not differ from those in the BR-fed group but were
      higher than in other groups. However, pools of propionate and butyrate with the
      RO diet were significantly lower than with diet BR and the same as with diets WR
      and RB. Portal venous VFA concentrations were unaffected by diet. The higher
      large bowel digesta masses and VFA with diet BR may reflect the escape of starch
      from the small intestine.

PMID- 8260478
TI  - The effect of graded inclusion of baked beans (Phaseolus vulgaris) on plasma and
      liver lipids in hypercholesterolaemic pigs given a Western-type diet.
AB  - The aim of the present study was to measure the effect of graded inclusion of
      baked beans (Phaseolus vulgaris) on plasma and liver lipids in
      hypercholesterolaemic pigs fed on a Western-type diet. Twenty-four Large White x
      Landrace pigs of about 30 kg body weight were made hypercholesterolaemic by
      feeding a semi-purified diet, high in saturated fat and supplemented with 10 g
      cholesterol/kg, for 14 d. After that, six pigs were randomly assigned to one of
      the four experimental groups. They received their respective diets, containing 0,
      100, 200 or 300 g baked beans/kg, on a dry-matter basis, for a further 28 d.
      Fasting blood samples were taken and analysed for total plasma cholesterol,
      lipoproteins and triacylglycerols. After the pigs were slaughtered at the end of
      the study, livers were analysed for their cholesterol content. Consumption of
      baked beans at 100, 200 and 300 g/kg reduced plasma total cholesterol by 5.3,
      20.2 and 35.6% respectively. However, only the diet with 300 g baked beans/kg
      showed a significant reduction (P < 0.05) compared with the control (without
      baked beans). The level of low-density-lipoprotein-cholesterol was also
      significantly (P < 0.05) reduced by 48% at 300 g baked beans/kg. Plasma very-low
      density-lipoprotein-cholesterol, high-density-lipoprotein-cholesterol and
      triacylglycerol contents were not affected by bean consumption. The supplements
      of 200 and 300 g baked beans/kg promoted a significant (P < 0.05) reduction of
      about 50% in cholesterol deposition in the liver, compared with the control.

PMID- 8260479
TI  - Effects of oat and rye fractions on biliary and faecal bile acid profiles in
      Syrian golden hamsters (Mesocricetus auratus).
AB  - The effects of bran and starchy endosperm fractions of oat and rye on faecal
      weight and on biliary and faecal bile acids were studied in Syrian golden
      hamsters (Mesocricetus auratus). The animals fed on diets supplemented with steam
      flaked oat bran, oat bran or rye bran had higher wet and dry weights of faeces
      compared with the animals fed on the fibre-free or low-fibre endosperm diets. A
      higher mean percentage of biliary cholic acid and a lower mean percentage of
      chenodeoxycholic and lithocholic (LCA) acids was observed in the bran
      supplemented dietary groups. Animals fed on the bran-supplemented diets had
      increased daily faecal excretion of both total saponifiable and total free bile
      acids compared with the animals fed on fibre-free or endosperm-supplemented
      diets. The mean percentage of total saponifiable bile acids in the faeces was
      higher, and that of free bile acids lower in the animals fed on bran-supplemented
      diets. A significantly lower concentration of faecal free LCA was observed in the
      animals fed on the rye-bran diet. Both bran and endosperm diets reduced the
      faecal LCA:deoxycholic acid compared with the fibre-free diet, but the bran diets
      had a more pronounced effect than endosperm diets.

PMID- 8260480
TI  - Digestion of polysaccharides and other major components in the small and large
      intestine of pigs fed on diets consisting of oat fractions rich in beta-D-glucan.
AB  - The digestibility of polysaccharides and other major components and the metabolic
      response of the microflora in the small and large intestines to oat diets varying
      in mixed linked beta(1-->3; 1-->4)-D-glucan (beta-glucan) were studied in
      experiments with ileum-cannulated pigs. The oat fractions for diets were prepared
      in a dry milling process in which oat groats were milled into two endosperm
      fractions (oat flour 1 and oat flour 2) and oat bran. The digestibility of
      polysaccharides and the metabolic response of the microflora were followed for
      the two contrasting diets, oat flour 1 and oat bran, from ingestion to excretion
      while the digestibility of oat groats and oat flour 2 were estimated only at the
      ileum and in faeces. There was no degradation of beta-glucan from either oat
      flour 1 or bran in the stomach and the first, middle and distal thirds of the
      small intestine (average digestibility approximately 0), while in the terminal
      ileum digestibility increased to 0.30 to 0.17 respectively. The digestion of
      starch in the first third of the small intestine was lower for the high-beta
      glucan oat-bran diet (0.49) than for the low-beta-glucan flour diet (0.64).
      However, digestibility differences between the two diets levelled out as the
      digesta moved aborally in the small intestine and the digestibility at the
      terminal ileum was almost complete (0.970-0.995) for all diets. Oat non-starch
      polysaccharides (NSP) were an easily digestible energy source for the microflora
      in the large intestine less than 13% of dietary NSP being recovered in faeces.
      The bulk of beta-glucan which survived the small intestine was degraded in the
      caecum and proximal colon while arabinoxylan was more slowly degraded. The amount
      of residues passing the ileo-caecal junction has little impact on the density of
      micro-organisms in the large intestine, which on the flour and bran diets were in
      the range of 10(10)-10(11) viable counts/g digesta, but a high impact on the
      activity of the flora in colon. Oat bran resulted in a higher proportion of
      butyric acid in large intestinal content compared with the flour diet. The faecal
      bulking effect of oat bran was mainly caused by an increased excretion of protein
      and fat, presumably of bacterial origin. Of all the diets tested the oat-bran
      diets had the lowest digestibilities of protein and fat at the terminal ileum and
      in the faeces.

PMID- 8260481
TI  - Adaptation to the digestion of non-starch polysaccharide in growing pigs fed on
      cereal or semi-purified basal diets.
AB  - Pigs (25-45 kg) were fed on either cereal or semi-purified basal diets
      supplemented with either high or low levels of sugar-beet pulp or wood cellulose
      (Solka-floc). The apparent digestibility and retention of N and apparent
      digestibility and metabolizability of energy (GE) and the apparent digestibility
      of non-starch polysaccharides (NSP) and their constituent monomers were measured
      during weeks 2, 4 and 6 of the trial. N and GE were less well-digested, retained
      or metabolized from cereal basal diets than from the corresponding semi-purified
      diets during all three periods. NSP from sugar-beet pulp was highly digestible,
      unlike that from Solka-floc which was relatively poorly digested. These
      differences of NSP digestibility were seen more clearly when incorporated in semi
      purified diets. There was no significant increase in the digestibility or
      retention of N, or digestibility or metabolizability of GE, or in the
      digestibility of sugar-beet pulp NSP with increasing time-period on the diets. In
      contrast, the digestibility of Solka-floc NSP tended to increase with the time
      period. The digestibility of NSP from the semi-purified diet with the high level
      of Solka-floc inclusion was much lower than that for the low level of inclusion,
      indicating that microbial activity had been reduced. In conclusion, adaptation to
      the diets in terms of N and GE balance may be complete after 1 week, but 3-5
      weeks may be necessary before stability of measurements of the digestibility of
      resistant NSP monomers can be obtained.

PMID- 8260482
TI  - Gastrointestinal responses to oats consumption in young adult and elderly rats:
      digestion, large bowel fermentation and crypt cell proliferation rates.
AB  - The present experiment was designed to test the hypothesis that ageing modifies
      the gastrointestinal responses to a change in diet composition. Rats of the
      Wag/Rij strain, either young adult (4 months of age) or elderly (27 months of
      age), were given a basal semi-purified diet or a diet of similar major nutrient
      composition containing 500 g oatmeal/kg for 17-18 d. Elderly rats digested the
      dry matter (DM) and organic matter (OM) of both diets less well than did their
      young adult counterparts, with more of this digestion occurring in the distal
      intestine. The greater flow of OM to the caecum of oats-fed animals was
      accompanied by significant reductions in caecal pH and increases in caecal total
      short-chain fatty acids (SCFA) concentration which appeared to be independent of
      age. However, young adults responded to feeding on oats by showing a much larger
      increase in the molar proportion of butyrate (332%) than did elderly animals
      (79%). Elderly rats had longer duodenal villi than did young adults but effects
      of age or diet were not detectable at other sites. With both age-groups oats
      consumption was associated with significant stimulation of crypt cell
      proliferation rate (CCPR) in the small intestine and caecum, but for the colon
      there was a significant reduction in CCPR with oats feeding. A reduced ability of
      the aged large bowel (LB) to produce butyrate may contribute to the prevalence of
      LB disorders in the elderly.

PMID- 8260483
TI  - Thyroid function in rats with iodine deficiency is not further impaired by
      concurrent, marginal zinc deficiency.
AB  - The hypothesis tested was that Zn deficiency aggravates impaired thyroid function
      as induced by I deficiency. In two separate experiments male rats were fed on
      diets either deficient in Zn or in I, or deficient in both. An identical,
      restricted amount of food was given to each rat so that body-weight gain of the
      experimental groups was comparable. Zn deficiency was evidenced by reduced tibial
      Zn concentrations. I deficiency was evidenced by goitre, reduced urinary I
      excretion, reduced plasma thyroxine concentrations and reduced absolute amounts
      and concentrations of thyroxine in the thyroid. Zn deficiency had no effect on
      the raised thyroid weight as induced by I deficiency. Zn restriction from 184
      mumol Zn/kg diet to 31 mumol Zn/kg diet, but not to 92 mumol Zn/kg diet,
      significantly lowered plasma thyroxine concentration. There were no interrelated
      effects of Zn and I deficiencies on thyroid hormone levels. These results
      indicate that marginal Zn deficiency does not influence thyroid hormone
      metabolism in I deficiency.

PMID- 8260484
TI  - Interrelationship between vitamin A, iodine and iron status in schoolchildren in
      Shoa Region, central Ethiopia.
AB  - A total of 14,740 schoolchildren in seven provinces of Shoa Administrative Region
      in Central Ethiopia were surveyed for the prevalence of goitre, xerophthalmia and
      anaemia. Haemoglobin and packed cell volume were assessed in 966 children in one
      province while an in-depth study was conducted on 344 children in the same
      province and two others. Goitre, xerophthalmia (Bitot's spots) and clinical
      anaemia were observed in 34.2, 0.91 and 18.6% respectively of the children. Most
      biochemical variables were within the normal range while those of haemoglobin
      (Hb), mean corpuscular Hb concentration (MCHC) and urinary I excretion were
      lower, and mean corpuscular volume, mean corpuscular Hb (MCH), and
      immunoglobulins G and M were higher. Hb was strongly correlated with retinol,
      ferritin, MCHC, MCH, packed cell volume and erythrocyte count while retinol
      formed a triad with transthyretin (TTR) and retinol-binding protein (RBP) which
      were all correlated with one another. Total and free thyroxin and total and free
      triiodothyronine were positively correlated as were the concentrations of the
      total and free hormones. Thyrotropin (TSH) was negatively correlated with total
      and free thyroxin and positively correlated with free triiodothyronine. Thyroxin
      and triiodothyronine in both free and combined forms were all correlated with
      thyroxin-binding globulin which in turn was negatively correlated with the triad
      retinol, RBP and TTR. The triad was also negatively correlated with C-reactive
      protein. Urinary I excretion was positively associated with total thyroxin and
      negatively associated with TSH. The anaemia found was not nutritional in origin
      but due to the effect of infestation with intestinal parasites and malaria.

PMID- 8260485
TI  - Effect of iron deficiency on the digestive utilization of iron, phosphorus,
      calcium and magnesium in rats.
AB  - The influence of the source of dietary Fe (ferric citrate alone or mixed with
      bovine blood at a proportion of 1:1 (v/v)) on the digestive utilization of Fe, P,
      Ca and Mg, and on haemoglobin regeneration efficiency (HRE) was investigated in
      control and Fe-deficient rats. Diet A contained (by analysis) 43.5 mg Fe/kg diet
      (as ferric citrate), and diet B contained 44.3 mg Fe/kg diet (ferric citrate
      bovine blood). In Fe-deficient rats fed on diet A or B the apparent digestibility
      coefficient (ADC) of Fe increased by 42.3 and 45.7% respectively. The ADC of Ca
      and Mg decreased significantly in Fe-deficient rats regardless of the source of
      dietary Fe. The HRE increased by 72.9% in Fe-deficient rats fed on diet A, and by
      91.1% in Fe-deficient animals fed on diet B. In Fe-deficient rats fed on Fe for
      10 d the values of haematological variables approached normality. However, serum
      Fe remained low, indicating that Fe reserves were still depleted. A deficient
      dietary supply of Fe for 30 d did not significantly modify the numbers of
      circulating leucocytes.

PMID- 8260486
TI  - Antioxidant enzyme activity in the muscles of calves depleted of vitamin E or
      selenium or both.
AB  - Feeding diets depleted of vitamin E and Se to cattle can induce a disease known
      as nutritional degenerative myopathy. It is believed that an increased
      peroxidative challenge in muscle is involved in the pathogenesis of this disease.
      A number of species can up-regulate the activity of some antioxidant enzymes,
      including glutathione reductase (EC 1.6.4.2), glutathione transferase (EC
      2.5.1.18), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), catalase (EC
      1.11.1.6), and superoxide dismutase (EC 1.15.1.1), in an attempt to mitigate the
      effects of a peroxidative challenge. A 2 x 2 factorial study was set up to
      examine possible changes in the activities of these antioxidant enzymes in
      muscles of ruminant calves fed on diets low in either vitamin E or Se. Four
      groups of four calves each were fed on a basal diet of NaOH-treated barley which
      was supplemented with alpha-tocopherol or Se or both for a total of 50 weeks.
      Calves fed on diets depleted of vitamin E, but not those fed on diets low in Se,
      developed subclinical myopathy, as judged by increases in the activity of plasma
      creatinine kinase (EC 2.7.3.2), and had increased muscle concentrations of two
      indices of lipid peroxidation, namely thiobarbituric acid-reactive substances,
      with and without ascorbate activation. Feeding diets depleted of vitamin E and
      diets low in Se both increased muscle activities of glucose-6-phosphate
      dehydrogenase in heart, biceps and supraspinatus. This change may have occurred
      in an attempt to maintain intracellular pools of reduced glutathione. No other
      changes in antioxidant enzyme activity were observed.

PMID- 8260487
TI  - The effect of condensed tannins in Lotus pedunculatus on the digestion and
      metabolism of methionine, cystine and inorganic sulphur in sheep.
AB  - Two experiments were conducted with sheep fed on fresh Lotus pedunculatus
      containing 50-55 g condensed tannin (CT)/kg dry matter. Effects of CT were
      assessed by comparing control sheep (CT operating) with sheep receiving a
      continuous intraruminal infusion of polyethylene glycol (PEG) to bind and
      inactivate CT. Digestion of methionine and cystine was determined using a
      continuous intraruminal infusion of indigestible markers, whilst plasma
      irreversible loss (IRL) of methionine, cystine and inorganic sulphate was
      determined using 35S labelling. The proportion of microbial non-NH3-N (NAN) in
      whole rumen digesta NAN and the IRL of reducible S from the rumen were determined
      using a continuous intraruminal infusion of (NH4)2(35)SO4. The proportion of
      microbial NAN in whole rumen digesta NAN (0.44 v. 0.71) and the IRL of reducible
      S from the rumen (0.84 v. 2.49 g S/d) were lower in control than PEG sheep. PEG
      sheep lost 30% of ingested methionine and cystine across the rumen, whereas the
      control sheep lost no methionine and cystine across the rumen. Apparent
      absorption of methionine from the small intestine was 27% higher in control than
      PEG sheep, but both groups had a similar apparent absorption of cystine. The
      apparent digestibility of cystine in the small intestine was lower in control
      (0.42) than PEG (0.53) sheep, whereas the apparent digestibility of methionine
      was similar (0.78) for both groups. CT had no effect on plasma methionine IRL,
      but markedly increased the IRL of cystine (39.8 v. 22.4 mumol/min) and reduced
      the IRL of plasma inorganic sulphate (35.9 v. 50.2 mumol/min). A three-pool model
      comparing interconversions between the three plasma metabolites showed that CT
      increased the flow of cystine to body synthetic reactions (36.5 v. 17.3
      mumol/min). This was due to trans-sulphuration of methionine to cystine being
      greater in control than in PEG sheep, whilst the oxidation of both methionine and
      cystine were reduced in control sheep. It was concluded that CT reduced the
      proteolysis of forage protein and the degradation of S amino acids to inorganic
      sulphide in the rumen, resulting in increased net absorption of methionine and
      increased utilization of cystine for body synthetic reactions in sheep with a
      high capacity for wool growth (and, hence, high cystine requirement).

PMID- 8260488
TI  - Marker methods for measuring digesta flow.

PMID- 8260489
TI  - Interaction between photoactivated rhodopsin and its kinase: stability and
      kinetics of complex formation.
AB  - Rhodopsin phosphorylation is a key event in the deactivation of this G-protein
      coupled receptor. Rhodopsin kinase mediates the reaction and requires specific
      cytoplasmic loop domains on rhodopsin, distinct from the sites of
      phosphorylation, for binding and activation. In this study, we characterize the
      formation of a stable complex between photolyzed rhodopsin in native washed disk
      membranes and its kinase. Centrifugation of the membranes after illumination and
      subsequent polyacrylamide gel electrophoresis demonstrates light-dependent
      binding of rhodopsin kinase to the membranes. A real-time monitor for the
      transition of the solubilized kinase into the bound state is provided by flash
      induced light-scattering binding signals. The complex has the following
      characteristics: (i) the on-rate of the reaction rises in linear proportion to
      the concentrations of both the kinase and photoactivated rhodopsin; kinetic
      analysis yields a bimolecular rate constant of kon = 0.5-1 microM-1s-1. (ii) The
      dissociation constant of the complex is 0.3 < KD < 0.5 microM in the absence of
      ATP, but with ATP, it decreases by at least a factor of 10; however,
      phosphorylation of rhodopsin or (auto)phosphorylation of rhodopsin kinase leads
      to destabilization of the complex. (iii) In contrast to the binding of arrestin
      and transducin, the binding of rhodopsin kinase to photoactivated rhodopsin does
      not stabilize the metarhodopsin II photoproduct; however, rhodopsin kinase
      competes with the G-protein transducin for binding to photoactivated rhodopsin.
      Extrapolation of the kinetic parameters to cellular concentrations at room
      temperature suggests that free competitive binding of the kinase would strongly
      inhibit the G-protein activation process after a few hundred catalytic cycles.

PMID- 8260490
TI  - Solution structure of the DNA methyl phosphotriester repair domain of Escherichia
      coli Ada.
AB  - The Escherichia coli Ada protein repairs methyl phosphotriesters in DNA by
      direct, irreversible methyl transfer to one of its own cysteine residues. The
      methyl-transfer process appears to be autocatalyzed by coordination of the
      acceptor residue, Cys-69, to a tightly bound zinc ion. Upon methyl transfer, Ada
      acquires the ability to bind DNA sequence-specifically and thereby to induce
      genes that confer resistance to methylating agents. The solution structure of an
      N-terminal 10-kDa fragment of Ada, which retains zinc binding and DNA methyl
      phosphotriester repair activities, was determined using multidimensional
      heteronuclear nuclear magnetic resonance techniques. The structure reveals a zinc
      binding motif unlike any observed thus far in transcription factors or zinc
      containing enzymes and provides insight into the mechanism of metalloactivated
      DNA repair.

PMID- 8260491
TI  - Crystal structures of the Klenow fragment of DNA polymerase I complexed with
      deoxynucleoside triphosphate and pyrophosphate.
AB  - Crystal structures of the Klenow fragment (KF) of DNA polymerase I from
      Escherichia coli complexed with deoxynucleoside triphosphate (dNTP) or with
      pyrophosphate (PPi) determined to 3.9-A resolution by X-ray crystallography show
      these molecules binding within the cleft of the polymerase domain and surrounded
      by residues previously implicated in dNTP binding. The dNTP binds adjacent to the
      O-helix [Ollis, D. L., Brick, P., Hamlin, R., Xuong, N. G., & Steitz, T. A.
      (1985a) Nature 313, 762-766] with its triphosphate moiety anchored by three
      positively charged residues, Arg 754, Arg 682, and Lys 758, plus His 734 and Gln
      708. The dNTP binding site observed in the crystal is consistent with the results
      of chemical modification including cross-linking and is also near many of the
      amino acid residues whose mutation affects catalysis [Polesky, A. H., Steitz, T.
      A., Grindley, N. D. F., & Joyce, C. M. (1990) J. Biol. Chem. 265, 14579-14591;
      Polesky, A. H., Dahlberg, M. E., Benkovic, S. J., Grindley, N. D. F., & Joyce, C.
      M. (1992) J. Biol. Chem. 267, 8417-8428]. However, we conclude that the position
      of at least the dNMP moiety of dNTP in the binary complex is not likely to be the
      same as in its catalytically relevant complex with primer-template DNA.

PMID- 8260492
TI  - Molecular properties of pyruvate formate-lyase activating enzyme.
AB  - Pyruvate formate-lyase is a radical-containing enzyme that catalyzes the
      nonoxidative cleavage of pyruvate via a postulated homolytic mechanism. The
      formation of this enzymic radical in vitro requires an activating system composed
      of PFL-activating enzyme, S-adenosylmethionine, ferrous ion, a reduced flavin,
      DTT, and pyruvate as an allosteric effector. The need for large quantities of PFL
      activating enzyme for biochemical and biophysical studies on the mechanism of
      protein radical formation has prompted us to clone the act gene and overexpress
      the gene product in Escherichia coli. Using PCR technology, the act gene was
      isolated and subcloned into various expression vectors. The overexpression of the
      protein was as high as 30-50% of the total cellular protein. However, the
      majority of the protein resided in the form of insoluble inclusion bodies. A
      procedure was developed to denature and isolate the inclusion bodies followed by
      refolding under anaerobic conditions. This purification method affords 5 mg of
      purified protein from 1 g of cells. Biochemical characterization demonstrated
      that the enzyme can bind one Fe(II) per protein monomer, and the protein did not
      exhibit any visible chromophore as previously observed. Co(II) and Cu(II) can be
      reconstituted into the protein with similar stoichiometries. Kinetic studies
      showed that the rate of radical formation was independent of ionic strength and
      the Km's for SAM and inactive PFL were determined to be 2.8 and 1.2 microM,
      respectively. Fluorescent binding data revealed that the Kd for SAM binding to
      the activating enzyme alone was comparable to the Km for SAM in the PFL
      activation indicating that the binding site for SAM resides on AE.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260493
TI  - Stereochemistry of metal ion coordination to the terminal thiophosphoryl group of
      adenosine 5'-O-(3-thiotriphosphate) at the active site of pyruvate kinase.
AB  - Epimers of [gamma-17O]adenosine 5'-O-(3-thiotriphosphate) ([gamma-17O]ATP gamma
      S) have been used to determine the stereochemistry of Mn2+ coordination to the
      terminal thiophosphoryl group in complexes of pyruvate kinase, oxalate, ATP gamma
      S, and Mg2+, Zn2+, Co2+, or Cd2+. The complex of pyruvate kinase with oxalate and
      ATP binds 2 equiv of divalent cation per active site. The terminal phosphoryl
      group of ATP in this enzymic complex becomes a chiral center as a result of
      coordination to both divalent metal ions. Electron paramagnetic resonance (EPR)
      data for complexes of pyruvate kinase with Rp- or Sp-[gamma-17O]-ATP gamma S,
      [17O]oxalate, and mixtures of Mn2+ with Mg2+, Zn2+, or Co2+ show that Mn2+ binds
      selectively at the site defined by coordination to oxalate and the pro-R oxygen
      of the thiophosphoryl group of ATP gamma S. In mixtures containing Mn2+ and Cd2+
      with Tl+ as the monovalent cation, two hybrid complexes form, enzyme-oxalate-MnII
      ATP gamma S-CdII and enzyme-oxalate-CdII-ATP gamma S-MnII, as in the analogous
      complexes with ATP and K+ or Tl+ (Buchbinder, J. L., & Reed, G. H. (1990)
      Biochemistry 29, 1799-1806). In the enzyme-oxalate-MnII-ATP gamma S-CdII species,
      Mn2+ binds exclusively to the pro-R oxygen of the thiophosphoryl group. In the
      enzyme-oxalate-CdII-ATP gamma S-MnII species, Mn2+ binds to the pro-R oxygen
      (60%) and to the pro-S oxygen (40%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260494
TI  - Hydrophobic C-terminal amino acids in the beta-subunit are involved in assembly
      with the alpha-subunit of Na,K-ATPase.
AB  - To define the structural basis of oligomerization for the alpha- and beta
      subunits of Na,K-ATPase, we have attempted to identify the amino acids in the C
      terminus of the beta-subunit that are involved in subunit assembly. We predicted
      that the last 10 amino acids form a beta-strand-like structure exposing on one
      side a hydrophilic and on the other side a continuous hydrophobic domain. The
      relative importance of the two domains in assembly was probed by introducing
      point mutations in either domain of Xenopus beta 3-subunits and by testing the
      ability of these mutants to stabilize newly synthesized alpha-subunits expressed
      in Xenopus oocytes and to form functional alpha-beta complexes at the plasma
      membrane. All single and double mutants with changes at R268 and/or K272 to
      either uncharged or negatively charged amino acids associated with coexpressed
      alpha-subunits and increased the number of ouabain binding sites and Rb uptake
      into oocytes. On the other hand, mutations affecting the hydrophobic amino acids
      influenced the assembly efficiency with alpha-subunits to a variable extent. The
      single mutants V269N and I275N did not influence and the mutant V273N slightly
      affected the assembly process. On the other hand, the cellular accumulation of
      alpha-subunits and the expression of functional Na,K pumps was considerably
      reduced with the mutant F271N and totally abolished with the double mutant
      V269N/F271N. Finally, replacement of V269 and F271 or V273 and I275 with the less
      hydrophobic alanine also significantly decreased subunit assembly, which was no
      longer detectable after replacement of all four amino acids.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8260495
TI  - Preparation of active recombinant TIMP-1 from Escherichia coli inclusion bodies
      and complex formation with the recombinant catalytic domain of PMNL-collagenase.
AB  - TIMP-1 is a member of the family of tissue inhibitors of metalloproteinases
      involved in regulating the activity of extracellular matrix degrading
      metalloproteinases. The TIMP-1 cDNA was obtained by reverse transcription
      polymerase chain reaction (RT-PCR) amplification of the corresponding mRNA from
      human fibroblasts. Cloning and expression of the TIMP-1 cDNA were performed in
      Escherichia coli. In the host vector system chosen, rTIMP-1 is stored
      intracellularly in its denatured, insoluble form in inclusion bodies. We report a
      new method for the purification and renaturation of rTIMP-1 from E. coli
      inclusion bodies to an active inhibitor of matrix metalloproteinases (80% yield),
      presumably containing the correct assignment of the six disulfide bonds. A resin
      with the covalently bound recombinant catalytic domain of the PMNL-collagenase as
      the affinity ligand provided an effective means for the separation of correctly
      folded, active rTIMP-1 from inactive forms with mismatched disulfides. TIMP-1 and
      TIMP-2, the two most extensively examined members of the family of tissue
      inhibitors of metalloproteinases, are known to form a complex with the activated
      forms of most matrix metalloproteinases and the latent forms of the 92-kDa and 72
      kDa gelatinases, respectively. In this study, we report on the complex formation
      of the recombinant catalytic domain of the PMNL-collagenase with TIMP-1,
      nonglycosylated recombinant TIMP-1, and recombinant TIMP-2. The Ki values for the
      different inhibitors were determined in a kinetic assay using a fluorogenic
      substrate peptide. In this assay, rTIMP-2 had a more effective inhibitory
      capability against the recombinant catalytic domain of the PMNL-collagenase than
      TIMP-1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260496
TI  - An examination of the copper requirement of phenylalanine hydroxylase from
      Chromobacterium violaceum.
AB  - Phenylalanine hydroxylase from Chromobacterium violaceum (CVPAH) was classified
      as a copper metalloenzyme by virtue of a 1/1 Cu/enzyme stoichiometry and its
      inhibition with various chelators [Pember, S. O., Villafranca, J. J., & Benkovic,
      S. J. (1986) Biochemistry 25, 6611]. We have prepared "copper-free" CVPAH by
      extraction with DTT. These preparations retained full activity though the
      Cu/enzyme ratio averaged 0.015. Reconstitution by extraneous copper was disproved
      by measuring a Cu/enzyme ratio of 0.09 in assay mixtures after the specific
      activity was determined to be within 85% of a fully copper-complexed control.
      Several copper chelators were examined and were not inhibitory. The "copper-free"
      enzyme had significant activity without a thiol or other reducing agent capable
      of reducing the copper center whereas copper-complexed CVPAH had minimal activity
      under these conditions. Copper-complexed CVPAH can be activated, however, by
      nonreducing copper ligands such as imidazole. From these results, we conclude
      that copper is not a requirement of activity. Iron, cobalt, nickel, manganese,
      molybdenum, and chromium were not found in the "copper-free" preparation,
      indicating that the active hydroxylating species may not require a redox-active
      metal. The KdS for binding Cu2+ and Zn2+ were measured to be 0.48 and 0.85
      microM, respectively. Both copper and zinc were found to be potent inhibitors of
      "copper-free" CVPAH in the absence of thiols. DTT reverses inhibition due to Cu2+
      but not inhibition caused by Zn2+. The product stoichiometry indicates the same
      tightly coupled turnover found with all other pterin-dependent hydroxylases when
      using natural substrates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260497
TI  - Identification of Cys-150 in the active site of phosphomannose isomerase from
      Candida albicans.
AB  - Candida albicans phosphomannose isomerase (PMI) (EC 5.3.1.8) has been recently
      cloned and overexpressed in Escherichia coli. The enzyme can be irreversibly
      inactivated by iodoacetate in 50 mM borate buffer, pH 9.0, in a time-dependent
      manner at a rate of 4.2 +/- 0.03 min-1 M-1. This inhibition can be prevented by
      the substrate mannose 6-phosphate with a Ks of 0.22 +/- 0.05 mM, slightly lower
      than its Km value. However, metals such as zinc and cadmium, which are
      reversible, competitive inhibitors for PMI, do not protect the enzyme against
      modification. The protein has been labeled by using [2-14C]iodoacetate, in the
      presence or absence of substrate, and the protein is fully inactivated when 1.0
      thiol group is modified per molecule of enzyme. Tryptic maps of the modified
      protein have been produced. The protected peptide has been identified and
      sequenced, and the phenylthiohydantoin amino acids have been collected. The
      modified amino acid is Cys-150. This cysteine residue is conserved in mammalian
      and yeast phosphomannose isomerases, but not in bacterial species where it is
      replaced with asparagine. We therefore purified PMI from E. coli and showed that
      this enzyme is not sensitive to inactivation by iodoacetate. The iodoacetate is
      presumably inhibiting PMI by sterically blocking the mannose 6-phosphate binding
      site. Multiple sequence alignment procedures were used to try to identify
      potential ligands of the zinc atom that is essential for enzyme activity and thus
      to delineate the active site region.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260498
TI  - Binding and electron transfer reactions between methanol dehydrogenase and its
      physiologic electron acceptor cytochrome c-551i: a kinetic and thermodynamic
      analysis.
AB  - The quinoprotein methanol dehydrogenase and cytochrome c-551i form a physiologic
      complex in which electrons are transferred from pyrroloquinoline quinone to heme.
      The reoxidation of methanol dehydrogenase by the cytochrome was studied by
      stopped-flow spectroscopy. The rate constant for the electron transfer reaction
      and the dissociation constant for complex formation were each determined at
      temperatures ranging from 20 to 50 degrees C. The electron transfer rates varied
      from 1.4 to 4.6 s-1. Analysis of the electron transfer reaction by Marcus theory
      yielded values of 1.9 eV for the reorganizational energy and 0.071 cm-1 for the
      electronic coupling and predicted a theoretical distance between redox centers of
      15 A. Kinetically determined dissociation constants correlated well with a Kd of
      375 microM which was determined in a direct ultrafiltration binding assay.
      Thermodynamic analysis of the dissociation constants indicated the importance of
      the hydrophobic effect in complex formation.

PMID- 8260500
TI  - Structural changes in cytochrome c upon hydrogen-deuterium exchange.
AB  - The resonance Raman spectra of yeast ferri- and ferro-iso-1-cytochrome c
      dissolved in H2O and D2O are reported. Hydrogen exchange in the protein leads to
      distinct spectral changes of heme vibrational bands, particularly in the region
      between 670 and 710 cm-1 and at approximately 443 and approximately 450 cm-1. The
      latter two bands, which have previously been assigned to porphyrin modes
      including bending vibrations of the propionate side chains [Hildebrandt, P.
      (1991) J. Mol. Struct. 242, 379-395], reveal frequency shifts by up to 4 cm-1.
      These shifts are attributed to structural changes of the propionate groups caused
      by the energetic differences of the hydrogen and deuterium bonds between these
      substituents and the adjacent amino acid residues. The frequency shifts of the
      bands between 670 and 710 cm-1 most likely reflect structural differences of the
      tetrapyrrole macrocycle itself. Time-dependent experiments revealed that the
      hydrogen exchange processes associated with the changes in the resonance Raman
      spectra are complete in less than 15 min. The protons which are involved are
      those in the interior of the heme pocket as concluded by comparison with the
      exchange rate constants previously determined by NMR spectroscopy [Mayne, L.,
      Paterson, Y., Cerasoli, D., & Englander, S. W. (1992) Biochemistry 31, 10678
      10685]. These protons are part of a hydrogen bonding network including the amide
      protons of Asn-52, Met-80, and Lys-79, the side chain protons of Asn-52, Tyr-67,
      Thr-78, Trp-59, and Thr-49, and the water molecules 121 and 166.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260499
TI  - Resonance Raman and EPR spectroscopic studies on heme-heme oxygenase complexes.
AB  - The binding of ferrous and ferric hemes and manganese(II)- and manganese(III)
      substituted hemes to heme oxygenase has been investigated by optical absorption,
      resonance Raman, and EPR spectroscopy. The results are consistent with the
      presence of a six-coordinate heme moiety ligated to an essential histidine ligand
      and a water molecule. The latter ionizes with a pKa approximately 8.0 to give a
      mixture of high-spin and low-spin six-coordinate hydroxo adducts. Addition of
      excess cyanide converts the heme to a hexacoordinate low-spin species. The
      resonance Raman spectrum of the ferrous heme-heme oxygenase complex and that of
      the Mn(II)protoporphyrin-heme oxygenase complex shows bands at 216 and 212 cm-1,
      respectively, that are assigned to the metal-histidine stretching mode. The EPR
      spectrum of the oxidized heme-heme oxygenase complex has a strongly axial signal
      with g parallel of approximately 6 and g perpendicular approximately 2. 14NO and
      15NO adducts of ferrous heme-heme oxygenase exhibit EPR hyperfine splittings of
      approximately 20 and approximately 25 Gauss, respectively. In addition, both
      nitrosyl complexes show additional superhyperfine splittings of approximately 7
      Gauss from spin-spin interaction with the proximal histidine nitrogen. The heme
      environment in the heme-heme oxygenase enzyme-substrate complex has spectroscopic
      properties similar to those of the heme in myoglobin. Hence, there is neither a
      strongly electron-donating fifth (proximal) ligand nor an electron-withdrawing
      network on the distal side of the heme moiety comparable to that for cytochromes
      P-450 and peroxidases. This observation has profound implications about the
      nature of the oxygen-activating process in the heme-->biliverdin reaction that
      are discussed in this paper.

PMID- 8260501
TI  - Mutational analysis of the pea phytochrome A chromophore pocket: chromophore
      assembly with apophytochrome A and photoreversibility.
AB  - Ten site-specific mutants of pea apophytochrome A were expressed in Saccharomyces
      cerevisiae and analyzed for chromophore assembly with apoprotein and
      photoreversible absorbance changes. The mutants constitute two specific changes
      for each of five conserved amino acid residues located in the microenvironment of
      the chromophore attachment residue, which is Cys-323 in pea phytochrome A. All
      mutant apophytochromes were autocatalytically able to covalently attach
      phycocyanobilin, indicating that there were no major structural perturbations in
      the apoproteins. However, the rate of chromophore ligation varied significantly
      among the mutants. Spectrally, the mutant holophytochromes are of three types:
      mutant phytochromes that are indistinguishable from the wild-type adduct, mutants
      with blue-shifted Pr and Pfr absorption maxima compared to the wild-type adduct,
      and mutants that are not photoreversible. From an analysis of the results, we
      concluded that the residues Asp-309, Arg-318, His-321, and Gln-326 are probably
      not catalytically involved in the chromophore ligation reaction, but some
      residues may play significant structural and stereochemical roles. Arg-318 might
      anchor the chromophore, as has been suggested [Partis, M. D., & Grimm, R. (1990)
      Z. Naturforsch, 45c, 987-998; Parker, W., et al. (1993) Bioconjugate Chem. (in
      press)]. The conserved Gln-326, three residues downstream from the chromophore
      attachment site, is not electrostatically critical for the spectral integrity and
      photoreversibility of phytochrome, but this residue is sterically important to
      the lyase activity. It appears that the role of the five amino acid residues in
      the N- and C-terminal vicinities of the chromophore binding Cys-323 is structural
      rather than catalytic for the ligation reaction.

PMID- 8260502
TI  - The C-terminus and the Ca2+ low-affinity binding sites in bacteriorhodopsin.
AB  - Bacteriorhodopsin (bR) is found previously to have two high-affinity and four to
      six low-affinity Ca2+ binding sites. Our previous studies with site-directed
      mutation suggested that the two high-affinity sites are located within the
      protein and close to the retinal pocket. In order to investigate the location of
      the four to six low-affinity binding sites, we studied Ca2+ binding to deionized
      bR as well as its variant in which its C-terminus is removed by papain treatment.
      Potentiometric titration with Ca(2+)-selective electrodes were carried out and
      Scatchard plots were obtained from the titration data. We found that most of the
      low-affinity sites are eliminated upon removal of the C-terminus in bR. This
      suggests that the low-affinity sites in bR are on the surface. The involvement of
      the C-terminus in these sites is discussed.

PMID- 8260503
TI  - Rhodopsin activation: effects on the metarhodopsin I-metarhodopsin II equilibrium
      of neutralization or introduction of charged amino acids within putative
      transmembrane segments.
AB  - We have studied the metarhodopsin I (M I)-metarhodopsin II (M II) equilibria of
      expressed wild-type and mutant rhodopsins. We studied two classes of mutants with
      amino acid substitutions in or near the putative transmembrane segments: those in
      which a charged residue was replaced by a neutral residue (or in one case another
      charged residue) and those in which a neutral residue likely (or postulated) to
      be in proximity to the retinylidene Schiff's base was replaced by a charged
      residue. In the first class, we found mutants that abnormally favored M II
      (replacements of Asp-83, Glu-134, or Arg-135) as well as one that abnormally
      favored M I (replacement of Glu-122). In the second class, we found several
      mutants that abnormally favored M I, the most extreme being those in which
      glutamate replaced His-211 or Ala-292. These studies suggest that electrostatic
      forces play a major role in the energetics of the M 1-to-M II transition, and
      they indicate that electrostatic perturbation in the vicinity of the protonated
      retinylidene Schiff's base is a plausible mechanism for the change in its pKa
      that is associated with the M I-M II transition. They further suggest that the
      highly conserved pair of charged residues homologous to Glu-134 and Arg-135 may
      play a general role in agonist-dependent conformational changes in G-protein
      coupled receptors.

PMID- 8260504
TI  - Spectral detection of an intermediate preceding the excited state in the
      bacterial luciferase reaction.
AB  - The bioluminescent reaction of luciferase isolated from Vibrio harveyi, strain
      M17, was initiated by mixing the luciferase-bound flavin 4a-hydroperoxide
      intermediate, purified in advance, with a long-chain aldehyde (dodecanal or
      octanal) at -4 degree C. Measurements of absorbance changes from 300 to 600 nm
      during the course of the reaction revealed the existence of three sets of
      isosbestic points and three kinetic phases, the second of which parallels
      kinetically the decay of bioluminescence, measured concurrently. The absorbance
      changes in this second step and the decay of light emission exhibited similar
      deuterium isotope effects; this is postulated to be the step giving rise to the
      excited state and the enzyme-bound flavin 4a-hydroxide. The first step of the
      reaction, however, did not show an isotope effect; the intermediate thereby
      formed, observed here for the first time, is postulated to correspond to the
      luciferase-bound flavin 4a-peroxyhemiacetal.

PMID- 8260505
TI  - Metarhodopsin intermediates of the gecko cone pigment P521.
AB  - Cone visual pigments are responsible for color vision. Using low-temperature
      spectroscopy and linear/logarithmic time scale flash photolysis, we studied the
      photochemistry of the cone visual pigment P521 from the lizard Gekko gekko. We
      found both meta I and meta II intermediates in this cone pigment; meta I absorbs
      at 480 nm, and meta II absorbs at ca. 380 nm. The formation of meta I is a fast
      process with a lifetime of 2.8 microseconds for the slow component (pH 6.70, 8.0
      degrees C, 2% digitonin) compared to 2.1 microseconds for bovine rhodopsin under
      these conditions. The formation of meta II does not have single-exponential
      kinetics but can be better characterized by fast and slow components. High pH
      favors faster kinetics of meta II formation, but less is formed. The amount of
      meta II formed has a pKa of 8.7. The fast component of the meta II formation
      seems to have a somewhat lower pKa (e.g., 6.4). Temperature also affects meta II
      formation, with high temperature favoring a faster rate and larger amounts. The
      higher pKa of the meta I to meta II transition in gecko P521 compared to a rod
      pigment like bovine rhodopsin (pKa = 6.4) probably is due to a cysteine residue
      at position 211 in gecko rather than a histidine residue in bovine rhodopsin.

PMID- 8260506
TI  - Interaction of annexins with membranes: the N-terminus as a governing parameter
      as revealed with a chimeric annexin.
AB  - The modulating effect of the variable N-terminus of annexins on the properties of
      these Ca(2+)-binding proteins was investigated. To this end, the interaction of
      annexin V and a mutant annexin, INVC, consisting of the N-terminus of annexin I
      (amino acids 1-45) and the core of annexin V (19-320), with large unilamellar
      phosphatidylserine (PS) vesicles was examined. In contrast to annexin V, the
      mutant annexin mediated Ca(2+)-dependent aggregation of the lipid vesicles at
      neutral pH. However, annexin V induces Ca(2+)-dependent aggregation at mild
      acidic pH. Moreover, both proteins can engage in hydrophobic interactions with PS
      vesicles, which results in release of the vesicle contents. These membrane
      perturbing properties are expressed by both annexins in the absence of Ca2+ and
      occur at neutral and mild acidic pH. Interestingly, addition of Ca2+ inhibits
      annexin V-induced release, but sustains the release induced by the mutant annexin
      INVC. The Ca(2+)-dependent effects on the release of vesicle contents are
      reversed upon EDTA addition. Conformational changes revealed by binding of the
      hydrophobic probe, 4,4'-bis(1-anilino-8-naphthalenesulfonate), underly the
      observed Ca(2+)-modulated effects on leakage. However, low-pH-mediated
      aggregation by annexin V does not seem to be related to macroscopic
      conformational changes. Annexin INVC also affects Ca(2+)-induced fusion of PS
      vesicles, displaying synergistic properties in conjunction with Ca2+ at neutral
      pH. By contrast, annexin V does not display similar properties at mild acidic pH,
      in spite of its ability to aggregate vesicles under such conditions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260507
TI  - Kinetic and allosteric cooperativity in L-adenosine transport in chromaffin
      cells. A mnemonical transporter.
AB  - In cultured chromaffin cells and plasma membrane vesicles from chromaffin tissue,
      the transport of D-[3H]adenosine followed Michaelis-Menten saturation kinetics,
      with Km values of 1.5 +/- 0.3 microM and 1.9 +/- 0.2 microM, respectively. The
      transport of the isomer, L-[3H]adenosine, showed sigmoidal kinetics in both
      preparations. In plasma membrane vesicles the S0.5 was 2.5 +/- 0.2 microM with a
      Hill coefficient of 2.8 and the Vmax value of 0.26 +/- 0.01 pmol s-1 (mg of
      protein)-1. In cultured chromaffin cells the kinetic parameters for L
      [3H]adenosine were S0.5 = 6.2 +/- 0.2 microM and a Vmax 19.7 +/- 0.5 pmol/min per
      10(6) cells, with a pronounced positive cooperativity. The Hill coefficient was
      4.9. The transport of the L-isomer in cultured cells followed Michaelis-Menten
      kinetics at the lowest concentrations employed, below 2 microM. On the basis of
      these results, we propose a kinetic model whereby the adenosine transporter
      functions mnemonically.

PMID- 8260508
TI  - Nucleoside triples from the group I intron.
AB  - Oligonucleotides modeled on a proposed base-triple domain in the P4/P6 region of
      the self-splicing group I intron have been characterized by NMR. The NMR data
      indicate that single-stranded nucleotides in this domain are in the minor groove
      of an adjacent helix within hydrogen bonding distance of 2'-hydroxyl groups in an
      interaction we term a nucleoside triple. Oligonucleotides containing the two most
      frequently occurring sequences among group I introns in the P4/P6 region formed
      nucleoside triples in the minor groove, whereas oligonucleotides containing
      sequences which are not conserved did not form triples. Surprisingly, the
      structures of the nucleoside triples in the oligonucleotides containing the two
      most frequently occurring sequences are different. If this difference were
      maintained in the context of the whole intron, it would suggest that the triples
      are not directly involved in catalysis, but rather that the nucleoside triples
      function by aligning the helical domains within the catalytic core of the intron.

PMID- 8260509
TI  - Crystal structure determination and refinement at 2.3-A resolution of the lentil
      lectin.

PMID- 8260510
TI  - [Brucellosis].

PMID- 8260511
TI  - [Effect of ciprofloxacin on the phagocytosis of Escherichia coli by human
      polymorphonuclear leukocytes].
AB  - BACKGROUND: Brief exposure of bacteria to high concentrations of some
      antimicrobials enhanced their susceptibility to phagocytic killing by human
      polymorphonuclear leucocytes. This effect was defined as Post Antibiotic
      Leukocyte Enhancement or PALE. In this study we have investigated the effect of
      prior exposure of E. coli for ten minutes to 0.99 mg/l of ciprofloxacin and 0.40
      mg/l of meropenem. METHODS AND RESULTS: The pretreated bacteria were incubated
      for three hours in a mixture containing leukocytes and leukocytes plus serum (10%
      v/v). Leukocytes were prepared from blood of healthful volunteers and were
      extracting with ammonium chloride and differential centrifugation. At one hour
      intervals, aliquots were taken and added to basic water to dispute leukocytes and
      spread onto agar plates. Viable bacteria were counted. PALE of ciprofloxacin was
      higher than meropenem. CONCLUSION: Whether PALE is confirmed, it must be taken
      into consideration in dosage schedules.

PMID- 8260513
TI  - [Epidemiologic study of Lyme disease in Asturias].
AB  - BACKGROUND: The aim of this study was to confirm the Sierra del Sueve (Asturias)
      as an endemic area for Lyme's disease and determine the seroprevalence of this
      disease in inhabitants of this and other zones of Asturias. METHODS: A taxonomic
      study of 233 ticks in this county was carried out and the rate of infection by
      Borrelia burgdorferi was determined by culture in modified Kelly medium.
      Seroprevalence of Lyme's disease was studied by enzyme-immunoanalysis IgG-IgM in
      150 inhabitants from several counties of Asturias. RESULTS: The tick Ixodes
      ricinus is the most abundant species in the zone. All the cultures of Ixodes for
      Borrelia burgdorferi were negative. Among the farmers of the area of Sueve,
      seroprevalence of Lyme's disease was higher than in other population groups.
      CONCLUSIONS: The Sierra del Sueve is an endemic area of Lyme's disease because of
      the appropriate vector I. ricinus and the super-population of Fallow deer. In
      this county the percentage of asymptomatic seropositives for this disease is much
      higher than that of other zones in Spain.

PMID- 8260512
TI  - [Incidence of tuberculostatic-resistant Mycobacterium tuberculosis. Clinical
      aspects and impact on therapy and clinical course].
AB  - BACKGROUND: To know the incidence of Mycobacterium tuberculosis resistant to anti
      tuberculin drugs in addition to the clinical features, treatment and evolution of
      the patients. METHODS: This was a retrospective study of the clinical histories
      of patients with isolation of Mycobacterium tuberculosis with some type of
      resistance studied from January 1980 to April 1992. RESULTS: During the period
      studied 470 patients were diagnosed with tuberculosis by cultures. In 30 of these
      cases (6.4%) Mycobacterium tuberculosis resistant to Isoniazide (8), Streptomycin
      (6), Isoniazide + Rifampicin (4), Isoniazide + Streptomycin (3), Isoniazide +
      Ethambutol (2), Isoniazide + Rifampicin + Streptomycin (2), Isoniazide +
      Rifampicin + Ethambutol (2), Rifampicin (1), Ethambutol (1), Isoniazide +
      Pyrazinamide (1) and Isoniazide + Rifampicin + Streptomycin + Ethambutol (1) were
      isolated. Clinical information was obtained on 23 patients, with the most
      frequent clinical pictures being those of respiratory infection (15). Five cases
      occurred in HIV+ patients. The resistance was considered as primary in 58.97% of
      the cases with modifications in empiric treatment being necessary in 6 cases. In
      15 out of the 19 patients from whom the data of the follow up was obtained the
      evolution was good. CONCLUSIONS: Resistance to Mycobacterium tuberculosis was
      6.4%, with the high number of strains resistant to Rifampicin being of note. In
      79% of the cases in which follow up data was obtained the resistance had no
      impact on treatment due to the good evolution of the patients in relation with
      the treatment used.

PMID- 8260514
TI  - [Nosocomial bacteremia caused by Enterobacter spp.: epidemiology and prognostic
      factors].
AB  - BACKGROUND: The aim of this study was to establish the clinical and epidemiologic
      features of nosocomial bacteremia by Enterobacter spp. and to analyse its
      prognostic factors. METHODS: A prospective study of the episodes of nosocomial
      bacteremia by Enterobacter spp. with clinical significance, detected in a third
      level university hospital from January 1984 to December 1990 was performed.
      RESULTS: During the study period, 226 episodes of bacteremia by Enterobacter
      spp., of which 184 (81%) were of nosocomial origin (8.1% of all the nosocomial
      bacteremias), while 14% were polymicrobial. An increasing trend was observed in
      the number of episodes (1984 vs 1990) from 0.9 vs 1.8 episodes per 1,000
      admissions, respectively. The mean age was 57 years and the male/female relation
      was 2.4/1. The most frequent focus of origin was infection of the vascular
      catheter (43%), followed by intraabdominal catheter (21%), urinary tract (14%),
      and other foci (17%). Fifty-four percent of the patients had received antibiotics
      prior to the episode of bacteremia. Most of the cases were detected in the
      Intensive Care Units (ICU) (41%) and in the gastrointestinal surgery area (24%).
      Global mortality was 23%. Logistic regression analysis selected an entry site
      other than infection of the vascular catheter (odds ratio 6.1; CI [95%)] 2.0
      18.4), shock (odds ratio, 6; CI [95%], 1.6-21.9) and immunosuppressive treatment
      (odds ratio, 5; CI [95%], 1.5-16.2) as independent variables of bad prognosis.
      CONCLUSIONS: Enterobacter spp. is an important nosocomial pathogen taking fourth
      place in the ranking of nosocomial bacteremia by gram negative bacilli. It
      predominantly affects a population of patients admitted in the ICU and surgery.
      The intravascular catheter is a frequent entry site for nosocomial bacteremia by
      Enterobacter spp.

PMID- 8260515
TI  - [Adverse reactions to trimethoprim-sulfamethoxazole in AIDS patients].
AB  - BACKGROUND: The aim of the present was to evaluate the incidence of side effects
      to Trimethoprim-sulphamethoxazole (TMP-SMX) in 32 patients with AIDS and
      pneumonia by Pneumocystis carinii. METHODS: A retrospective study was carried out
      following a protocol which included all items related with the drug used.
      RESULTS: Side effects to TMP-SMX were seen in 75% of the patients treated with
      the most important and severe being at a cutaneous level. These severe reactions
      require withdrawal of the drug and its substitution by pentamidine in half of the
      cases, while in the remaining 25% the reactions were mild. To date none of the 9
      patients prophylactically treated with TMP-SMX have relapsed over 3 years of
      follow up while 4 out of the 9 treated with pentamidine have had relapsed.
      CONCLUSIONS: Trimethoprim-sulphamethoxazole is the ideal prophylactic drug for
      those who are able to tolerate it. Following review of the literature 2 schedules
      of tolerance induction were proposed for use in patients who have had previous
      reactions with this drug, including a rapid schedule and another slow schedule.

PMID- 8260516
TI  - [Thoracic actinomycosis].
AB  - BACKGROUND: Thoracic actinomycosis is an rare disease in our medium. This fact,
      together with the variability of its forms of presentation and the difficulty in
      isolating its etiologic agent, make its diagnosis, particularly difficult.
      METHODS: A series of 8 cases diagnosed in the years 1988, 1989 and 1990 in two
      centers (Hospital de Bellvitge-Princeps d'Espanya and Hospital de l'Esperanca) is
      described with evaluation of the clinical and analytical data and the therapy
      applied. RESULTS: Species were only identified in 3 cases with Actinomyces
      israelii in two and Actinomyces odontolyticus in the third. The proven
      association with Mycobacterium tuberculosis, the presence of distant septic
      metastasis and eosinophilic pleuritis as forms of presentation are of note.
      Medical treatment was penicillin or derivatives in all the cases except one which
      was treated with diagnostic/therapeutic segmentectomy. CONCLUSIONS: It is
      concluded that when any subacute involvement of the thoracic and/or
      pleuropulmonary wall specific cultures should be carried out to discard eventual
      thoracic actinomycosis.

PMID- 8260517
TI  - [Viral gastroenteritis].

PMID- 8260518
TI  - [Epidemiology of infections caused by Acinetobacter baumannii].

PMID- 8260519
TI  - [Intracranial cystic lesion in a patient from a rural environment].

PMID- 8260520
TI  - [Cavitary lung lesions in an immunosuppressed patient].

PMID- 8260521
TI  - [Evolution of fluoroquinolone sensitivity in Staphylococcus aureus isolated from
      hemocultures in a general hospital].

PMID- 8260522
TI  - [Are seroprevalence studies useful in Lyme disease?].

PMID- 8260523
TI  - [Tuberculosis, an old disease on the up-swing].

PMID- 8260524
TI  - [Resistance of Candida sp. to fluconazole in AIDS patients].

PMID- 8260525
TI  - Evaluation of the liver function of cirrhotic patients based on the formation of
      monoethylglycine xylidide (MEGX) from lidocaine.
AB  - Determination of the functional hepatic reserve is still controversial. Many
      tests have been proposed, but the assay based on formation of the lidocaine
      metabolite, monoethylglycine xylidide, seems to offer a promising approach to
      this problem. In this study we evaluated the effectiveness of the
      monoethylglycine xylidide test in the clinical evaluation of 31 cirrhotic
      patients submitted to three different therapeutic options (sclerotherapy,
      transjugular intrahepatic protosystemic shunt and surgical procedures) and in 1
      patient submitted to right hepatectomy for giant hepatic angioma. We found a
      statistically significant difference between Child A and C patients and between
      Child B and C patients. The test did not differentiate Child A from Child B
      patients. We found no correlation between the Child-Pugh score, serum bilirubin,
      albumin and prothrombin time. There were no differences among the three groups of
      patients that could be statistically related to their therapy. The
      monoethylglycine xylidide test seems to be an attractive alternative to previous
      methods for the evaluation of the functional hepatic reserve, but further studies
      are necessary to assess the prognostic value of the test in cirrhotics, to
      separate the independent contribution of portosystemic shunting and hepatocyte
      dysfunction to monoethylglycine xylidide formation, and to evaluate the test as a
      prognostic index in cirrhotic patients submitted to general surgery.

PMID- 8260526
TI  - Oxalate in the human thyroid gland.
AB  - Ninety-seven fixed surgical thyroid specimens and 63 unfixed and 40 fixed thyroid
      specimens from autopsies were examined for their oxalate content. Proteases were
      used to process the tissue, and the oxalate was determined with an enzymatic
      assay. The fixed samples were grouped into seven diagnostic categories (diffuse
      colloid goitre; partially diffuse, partially nodular colloid goitre; nodular
      colloid goitre; goitre with multifocal functional autonomy; non-functioning
      adenoma; unifocal functional autonomy; Graves' disease). The oxalate
      concentrations of the samples were mainly dependent on age and gender, which were
      distributed unequally among the seven diagnostic groups. In thyroid tissue from
      cases of Graves' disease, however, the concentration of oxalate was remarkably
      low and statistically different from those of four of the six other groups.

PMID- 8260527
TI  - Soluble interleukin-2 receptor and urinary neopterin concentrations in malignant
      lymphoma.
AB  - The serum concentrations of soluble interleukin-2 receptors and urine neopterin
      were studied in 82 patients with malignant lymphomas (25 patients with Hodgkin's
      disease and 57 patients with non-Hodgkin's lymphoma. Increases in soluble
      interleukin-2 receptors and in urinary neopterin were significantly correlated
      with the clinical phase of the disease. The average values in both Hodgkin's
      disease and non-Hodgkin's lymphoma patients suffering from the disease in its
      active phase were significantly higher than those of patients in complete
      remission. Neopterin concentrations (but not soluble interleukin-2 receptor
      concentrations) were also elevated in clinical stages III-IV of each disease.
      Urinary neopterin correlated directly and significantly with the erythrocyte
      sedimentation rate and inversely with haemoglobin. Finally, a longitudinal
      analysis showed a general tendency for the markers to return to normal values, in
      accordance with the favourable outcome of therapy; this was more evident for
      urinary neopterin than for soluble interleukin-2 receptors. These findings seem
      to confirm that soluble interleukin-2 receptors and especially urinary neopterin
      can be useful markers for monitoring and prognosis of malignant lymphomas.

PMID- 8260529
TI  - Comparison of apolipoprotein A-I values assayed in lyophilized and frozen pooled
      human sera by a non-immunochemical electrophoretic method and by immunoassay.
AB  - Various immunochemical assays are used for measuring the apolipoprotein A-I in
      human serum, but results obtained by these assays often cannot be compared owing
      to methodological problems, the lack of reference methods and inadequate
      standardization. The electrophoretic apolipoprotein A-I assay avoids the problems
      associated with antibody-antigen interaction. The method involves
      spectrophotometric measurement of the Coomassie blue eluted from the
      apolipoprotein A-I bands of human serum after electrophoresis in a gradient gel.
      The assay was linear from 0.5 to 4.0 micrograms of apolipoprotein A-I. Within
      assay variability was 3.2% and between-assay variability was 5.9%. Overall
      analytical recovery was 98%. The electrophoretic assay is suitable for the
      quantitation of apolipoprotein A-I in fresh, frozen or lyophilized serum pools.
      Analysis of 6 frozen serum pools showed a good correlation between this assay and
      an immunoturbidimetric assay (r = 0.96), and between this assay and consensus
      values (r = 0.99). Consensus values were derived from the results of different
      immunochemical assays performed in 6 laboratories in 3 different countries within
      3 years. The mean apolipoprotein A-I concentrations in 3 lyophilized serum pools
      were 1.04 +/- 0.02, 0.86 +/- 0.02, and 0.45 +/- 0.03 g/l (mean +/- SD) by
      electrophoretic assay. The consensus values for these pools were 1.04, 0.86, and
      0.43 g/l, respectively, as derived from the data of different immunochemical
      assay measurements performed in 84 laboratories in 34 various countries. The
      electrophoretic assay has been proposed as an alternative to the immunochemical
      assays for assigning the target values to reference and control materials, using
      pure and well-characterized apolipoprotein A-I as a primary standard.

PMID- 8260528
TI  - On the degree of platelet, coagulation and fibrinolysis activation after cerebral
      infarction and cerebral haemorrhage and the clinical outcome.
AB  - Thrombocytic, haemostatic and fibrinolytic quantities were investigated in 47
      patients with cerebral infarction and 34 patients with cerebral haemorrhage.
      Sixteen of the infarction patients and ten patients of the haemorrhage group were
      on acetylsalicylic acid medication. Of the remaining 55 patients without
      acetylsalicylic medication 21/31 = 67.7% of the patients in the infarction group
      and 9/24 = 37.5% of the patients in the bleeding group had unphysiologically
      enhanced ADP-induced platelet aggregation. With regard to the coagulation and
      fibrinolysis markers no significant differences were found between the two
      groups. In both groups, coagulation activity markers (fibrin monomer and thrombin
      antithrombin III), as well as D-dimers were significantly higher than in controls
      in a high proportion of cases. In 5/47 of the infarction patients and in 3/34 of
      the haemorrhage patients the fibrin monomer levels were elevated to such an
      extent, that it can be considered as low grade disseminated intravascular
      coagulation. In the cerebral haemorrhage group, 80.3% of the patients who
      subsequently died showed a significantly enhanced fibrin monomer concentration,
      compared with 28.6% of those who survived. The corresponding frequencies for D
      dimer were 100% compared with 66.7%. In the cerebral infarction group, the only
      analytical quantity showing a significant difference between patients with a
      fatal outcome and those with a non-fatal outcome was ADP (2 mumol/l) induced
      platelet aggregation (83.3% in the fatal group, 40.0% in the non-fatal group).

PMID- 8260530
TI  - Plasma carnitines: reference values in an ambulatory population.
AB  - Carnitine was determined radioenzymatically in the plasma of 415 hospital
      employees involved in a screening programme for prevention of major
      cardiovascular risks. A reference population (N = 340) was extracted after
      excluding subjects with hypertension, diabetes mellitus or treatment for
      hypercholesterolaemia. This population showed a Gaussian distribution for total
      and free carnitine concentrations both in females and males but not for acyl
      carnitine or the acyl/free ratio. Females had lower total and free carnitine
      concentrations but a higher ratio of acyl/free carnitine than males. These
      differences were not detectable in older subjects (35 years for the acyl/free
      ratio, 45 years for total and free carnitine concentrations). Females with a body
      mass index > 28 had a lower acyl/free ratio than their respective controls. The
      differences in carnitine concentrations indicate that sex and age should be
      matched in patients or experimental groups and controls in studies involving
      carnitine plasma concentrations.

PMID- 8260531
TI  - A new approach for the rapid detection of common and atypical aldehyde
      dehydrogenase alleles.
AB  - A strong protection against the development of alcoholism is exerted by a point
      mutation in the gene coding for low Km aldehyde dehydrogenase (ALDH), i.e. ALDH2.
      We report a non-radioactive method for determining the common and atypical human
      mitochondrial aldehyde dehydrogenase (ALDH2) genotypes. This method is based on
      the fact that the base change (G-->A) in Exon 12 of the ALDH2 gene abolishes an
      Eco57 I restriction site (CTGAAG-->CTAAAG). A GC-clamp attached oligonucleotide
      was designed to yield a 176 base pair product by the polymerase chain reaction.
      After amplification, the resulting fragment containing the normal nucleotide
      sequence is cut by Eco57 I into two segments (131 base pairs + 45 base pairs)
      while the fragment containing the mutated sequence remains intact (176 base
      pairs). These are visualized by staining with ethidium bromide on agarose gels
      without blotting, hybridization or autoradiography.

PMID- 8260532
TI  - Haemoglobin interference in the bichromatic spectrophotometry of NAD(P)H at
      340/380 nm.
AB  - The negative bias observed in the NADPH-based bichromatic measurement of glucose
      in haemolysates (da Fonseca-Wollheim, F., Heinze, K.-G. & Liss, E. (1992)
      Temperature-dependent matrix effect in the direct enzymatic measurement of blood
      glucose, this journal 30, 371-375) is caused by shifts in the UV absorbance of
      haemoglobin which affect the absorbance difference delta A340/380 nm. In model
      experiments with haemoglobin solutions, spectral changes resulting in decreases
      of the absorbance at 340 nm and/or increases at 380 nm were found to occur for
      the following three reasons: 1. Oxidation of haemoglobin-O2 with formation of
      Fe(III) derivatives. Methaemoglobin formation is accelerated by lowering the pH,
      raising the temperature from 25 to 37 degrees C or by adding organic phosphates
      (inositol hexakisphosphate, ATP). At pH 6, addition of plasma increases the rate
      of methaemoglobin formation, while at pH values > 7, haemoglobin-O2 is
      stabilised. The oxidation of haemoglobin-O2 in the presence of sodium lauryl
      sulphate is also accompanied by a decrease of delta A340/380 nm. The haemichromes
      formed in this reaction exhibit stable UV light absorptivity. 2. Increase in the
      temperature of the haemoglobin-O2 solution. It is shown that the temperature
      induced shifts in the haemoglobin-O2 absorptivity are reversible and that similar
      changes occur with the chemically more stable cyanomethaemoglobin. 3.
      Deoxygenation of haemoglobin-O2 at low pO2. Theoretically, the variation of
      factors influencing the pO2 (0.5) such as temperature, pH and allosteric
      effectors can also lead to changes in delta A340/380 nm.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8260533
TI  - A short evaluation of a new haematological analyser: the Cobas Argos 5 Diff.
AB  - In order to evaluate the Cobas Argos 5 Diff, a five-part differential
      haematological analyser, we performed a comparative study using our current
      analyser, the Toa E-5000, and the manual leukocyte differential. Samples (n =
      593) were collected from various departments in our hospital and were tested on
      both Cobas Argos 5 Diff and Toa E-5000. Regression lines were calculated for all
      standard haematological quantities. A group of 100 samples, including 50 negative
      (absence of flags) and 50 positive (presence of flags), on the Cobas Argos 5 Diff
      were randomly selected from the above-mentioned collection. All these samples had
      been checked under the microscope by two persons counting 200 cells each. The
      comparison of standard haematological quantities between Cobas Argos 5 Diff and
      the Toa E-5000 shows good correlation: Red Blood Cells r = 0.993; White Blood
      Cells r = 0.998; Haemoglobin r = 0.989; Haematocrit r = 0.982; Thrombocytes r =
      0.988; Lymphocytes (%) r = 0.983; Neutrophils (%) r = 0.959. The correlation
      between Cobas Argos 5 Diff and the manual leukocyte differential shows good
      correlation for lymphocytes and neutrophils, with acceptable correlation for
      eosinophils. The correlation for basophils and monocytes was less acceptable,
      especially for normal samples. We conclude that the efficiency of the Cobas Argos
      5 Diff is good (93%) and that it is a suitable haematological cell analyser.

PMID- 8260534
TI  - Regulation of M-CSF production by cultured human thymic epithelial cells.
AB  - We have studied the regulation of M-CSF production by human thymic epithelial
      cells (TEC) in a continuing effort to better understand the contribution of TEC
      to the intrathymic cytokine network. The levels of M-CSF were measured by
      radioimmunoassay. Five different TEC cultures were studied and we found that all
      cells examined produced M-CSF constitutively. We also studied the effects of
      cytokines on the regulation of the M-CSF secretion profile. IL-1, which strongly
      induces the secretion of a number of cytokines in TEC, was found to up-regulate M
      CSF levels. The effects of IL-1 were dose and time dependent suggesting a direct
      effect on TEC. IFN-gamma is known to up-regulate cell surface antigens, and to
      modulate the IL-1-induced cytokine response in TEC. IFN-gamma could induce M-CSF
      by itself, but the effects were less pronounced than those of IL-1. IFN-gamma did
      not modify the IL-1-induced M-CSF. IL-4, which has been shown to partially
      modulate the IL-1-induced GM-CSF in TEC, had no effect on constitutive or induced
      M-CSF levels. These data are discussed in the context of the regulation of
      myelopoietic growth factor production by thymic stromal cells.

PMID- 8260535
TI  - Interferon-gamma overcomes the glucocorticoid-mediated and the interleukin-4
      mediated inhibition of interleukin-1 beta synthesis in human monocytes.
AB  - Interleukin-1 (IL-1) has been implicated in the tissue destruction of rheumatoid
      arthritis, a disease that is widely treated with glucocorticoids. In this study
      we investigated the effect of the T cell product interferon-gamma (IFN-gamma) on
      the glucocorticoid-mediated and on the IL-4-mediated inhibition of IL-1 beta mRNA
      and IL-1 beta protein synthesis in highly purified human monocytes. Both
      dexamethasone and IL-4 dose-dependently inhibited IL-1 beta mRNA and IL-1 beta
      protein synthesis after stimulation with LPS (300 ng/ml); maximal inhibition of
      80-90% was achieved. IFN-gamma (1-100 U/ml) did not influence IL-1 beta mRNA and
      IL-1 beta protein levels in unstimulated cells, but potentiated the LPS-induced
      synthesis of IL-1 beta mRNA and IL-1 beta protein. After a preincubation time of
      1 h, 100 U/ml of IFN-gamma increased the LPS-induced IL-1 beta production by
      about 20-40%. When human monocytes were preincubated for 1 h with IFN-gamma (100
      U/ml) prior to the addition of dexamethasone (10(-6) M) and prior to the
      stimulation with LPS, the dexamethasone-mediated inhibition of IL-1 beta mRNA and
      IL-1 beta protein synthesis was totally neutralized by IFN-gamma. In addition,
      IFN-gamma totally overcame the negative effect of IL-4 (100 pM) on IL-1 beta
      protein synthesis. A preincubation period of at least 1 h with IFN-gamma was
      necessary for the neutralization of the dexamethasone effect. If IFN-gamma was
      given at the same time or after dexamethasone, only a weak effect was
      found.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260536
TI  - The role of lymphotoxin in the IL-2-driven differentiation of human lymphokine
      activated T-killer (T-LAK) cells in vitro.
AB  - Brief stimulation of human peripheral blood mononuclear cells with PHA and
      subsequent coculture with IL-2 results by 5 days in cultures of human lymphokine
      activated killer (T-LAK) cells. While IL-2 drives the proliferation of these
      cells in vitro, their maturation into functional effector cells capable of
      cytokine secretion and cell cytokines depends on the presence of other cytokines.
      The role of LT in the differentiation and proliferation of human T-LAK cells in
      vitro was investigated. Higher levels of LT than TNF were secreted by T-LAK cells
      during the first 5 days of the primary culture, then secretion levels dropped
      sharply. Human T-LAK cells cultivated with anti-LT rabbit antisera showed a
      slight reduction in growth compared to normal rabbit serum controls. In contrast,
      phenotypic analysis by FACS showed a decrease in CD4+ and an increase in CD8+
      populations of T-LAK cells in the treated cultures. Addition of LT from the
      beginning of the T-LAK cell culture resulted in an increase in CD4+ and a
      decrease in CD8+ cell populations at day 7. In addition, the cytolytic activity
      of non-MHC-restricted cytotoxicity and NK-like activity of anti-LT cultured T-LAK
      cells was also effected. These data indicated that LT may have a role in
      differentiation of IL-2 stimulated human T-LAK cells in vitro.

PMID- 8260537
TI  - Synergism between human recombinant monocyte chemotactic and activating factor
      and lipopolysaccharide for activation of antitumor properties in human blood
      monocytes.
AB  - Monocyte chemotactic and activating factor (MCAF) is an important mediator of
      monocyte recruitment to sites of chronic inflammation and neoplasia. In the
      present study, we determined whether MCAF can also enhance the activation of
      tumoricidal capacity of monocytes. Human monocytes incubated with MCAF and
      subthreshold concentrations of lipopolysaccharide (LPS) exhibited synergistic
      tumoricidal activity against allogeneic A375 melanoma cells, irrespective of
      their metastatic potential. The sequence of MCAF and LPS treatment was crucial.
      Monocytes treated first with MCAF for 4 h and then with LPS for 18 h were highly
      cytotoxic to the melanoma cells, whereas monocytes first treated with LPS and
      then with MCAF were not. Treatment of monocytes with MCAF and LPS also
      significantly increased production of tumor necrosis factor. These data suggest
      that like interferon-gamma, MCAF can prime human monocytes to respond to LPS.
      Interleukin-8, a chemokine for neutrophils, did not enhance the monocytes' LPS
      triggered tumoricidal response. Collectively, these data show that MCAF can
      influence the recruitment and tumoricidal activation of blood monocytes.
      Therefore, MCAF may be an important mediator of tumor regression.

PMID- 8260538
TI  - The CD4 surface antigen is induced and maintained on a T-lymphoid cell line by
      tumor necrosis factor-alpha.
AB  - We have used the L4E murine thymoma-derived T-lymphoid cell line to study
      mechanisms involved in CD4 expression. When L4E cells are cocultured with the St3
      stromal cell line, surface CD4 expression is maintained, even across a membrane.
      However, when transferred to medium alone, these cells rapidly lose CD4. We have
      tested whether CD4 can be maintained on CD4+ L4E cells when they are transferred
      to medium containing known cytokines. In these results, rmTNF-alpha maintained
      surface CD4 expression at significant levels on L4E cells. In addition, rmTNF
      alpha could induce CD4 on CD4- L4E cells (obtained by growth in medium alone).
      Despite these results CD4 induction and maintenance in L4E cells by coculture
      with St3 stroma did not appear to result from secretion of TNF-alpha, since St3
      cells did not express TNF-alpha mRNA, secreted TNF-alpha was not detected by
      ELISA assay in supernatant from St3 cells nor L4E-St3 cocultures, and incubation
      with neutralizing anti-TNF-alpha antibody did not inhibit CD4 maintenance. The
      ability of TNF-alpha to affect CD4 expression on L4E cells supports a role in
      thymocyte differentiation for this cytokine.

PMID- 8260539
TI  - Cytotoxicity and manganese superoxide dismutase induction by tumor necrosis
      factor-alpha and ionizing radiation in MCF-7 human breast carcinoma cells.
AB  - Both tumor necrosis factor-alpha (TNF) and ionizing radiation cause active-oxygen
      radical-mediated cell injuries and cell death. Thus cells treated by both TNF and
      radiation may suffer greater injuries than cells treated by either agent alone.
      On the other hand, TNF or radiation treatment can stimulate the expression of a
      mitochondrial superoxide scavenging enzyme, manganese superoxide dismutase
      (MnSOD), which can lower the cytotoxic effects of both agents. Thus, the
      induction of MnSOD by radiation may interfere with the cytotoxic action of TNF
      and vice versa. We used a human breast tumor cell line, MCF-7, to determine the
      interaction of TNF and radiation on cytotoxicity and MnSOD expression. TNF was
      found to be more effective as a cytotoxic agent when used before than after
      radiation treatment. These observations suggest that radiation induced-MnSOD was
      more effective in reducing the cytotoxic effect of TNF whereas TNF induction of
      MnSOD was less effective in counteracting the radiation action. Our results not
      only underscore the different effects of the treatment order of TNF and
      radiation, but also point to potential implication in the radiotherapy of breast
      tumors.

PMID- 8260540
TI  - The proline-rich motif (PRM): a novel feature of the cytokine/hematopoietin
      receptor superfamily.
AB  - Members of the cytokine receptor superfamily have been grouped together by
      function and by the presence of conserved amino acids in the extracellular
      domain, including four cysteine residues and the Trp-Ser-X-Trp-Ser (WSXWS) motif.
      However, no consensus sequence motif has been described in the intracellular
      domain of the cytokine receptors. We now report the presence of a proline-rich
      consensus sequence motif, eight amino acids in length, which is found in the
      intracellular domain of all the cytokine receptors. The proline-rich motif (PRM)
      can be divided into two complementary families that have superimposable consensus
      sequences. The consensus sequences were found by allowing similar amino acids
      (aliphatic = Al, aromatic = Ar) to be grouped together. The first motif (PRM1)
      has the sequence Al-Ar-Pro-X-Al-Pro-X-Pro, while the second (PRM2) is Ar-X-X-X-Al
      Pro-X-Pro. An overall consensus sequence for the PRM (PRM1 and PRM2) is derived
      by allowing aromatic and aliphatic residues to be considered hydrophobic (psi):
      psi-X-X-X-Al-Pro-X-Pro. Several alternative cytokine receptor isoforms contain
      two copies of the PRM within the same intracellular domain. The conservation of
      the proline-rich motif in cytokine receptors suggests that it plays a critical
      role in receptor function and defines a new feature of the cytokine receptor
      superfamily.

PMID- 8260541
TI  - Unconjugated and conjugated bilirubin pigments during perinatal development. IV.
      The influence of breast-feeding on neonatal hyperbilirubinemia.
AB  - One thousand four hundred and fifty-four consecutive full-term neonates,
      delivered over a period extending from February 1, 1991 to January 31, 1992 were
      prospectively studied during the first days of life to determine if breast
      feeding and hyperbilirubinemia were related. Six hundred and five infants were
      exclusively breast-fed on demand, 623 received both breast- and formula-feeding,
      and 226 were exclusively formula-fed. Of the 1,454 newborns studied, 70 (4.8%)
      presented with a bilirubin serum concentration > 12.9 mg/dl (4.62% in the breast
      fed group, 5.45% in the group fed with mother's milk with supplements, and 3.54%
      in the artificial formula group; the differences were not significant). Percent
      mean weight losses on the 3rd and 5th days were not significantly different.
      Babies breast-fed on demand seem to have a low incidence of hyperbilirubinemia
      similar to that found in formula-fed neonates.

PMID- 8260542
TI  - The use of intravenously administered immunoglobulins in the prevention of severe
      infection in very low birth weight neonates.
AB  - In a randomized prospective study in 116 selected neonates with very low birth
      weight, the effect of standard doses of intravenously administered
      immunoglobulins (IVIG) on the occurrence of severe infections was studied. No
      difference in infection rate or severity of infection could be observed between
      the treated neonates and the control group. The lack of effect could not be
      explained by an insufficient increase in the IgG serum levels, or inversely, by
      high immunosuppressive IgG levels. It is concluded that in very low birth weight
      neonates the administration of IVIG, under the conditions used in this
      investigation, does not protect against severe infection.

PMID- 8260543
TI  - Endocrine regulation of fetal adipose tissue metabolism in the pig: role of
      thyroxine.
AB  - This study was performed to characterize the role of thyroxine (T4) in the
      regulation of fetal adipose tissue metabolism. On day 70 of gestation, pig
      fetuses were hypophysectomized (hypoxed) by microcauterization. Both hypoxed and
      intact fetuses were implanted subcutaneously with T4 pellets or received no
      hormone replacement. Fetuses were removed by laparotomy on day 90 of gestation.
      Additional fetuses were hypoxed on day 70, implanted with T4 pellets on day 90
      and removed on day 105 of gestation. Serum T4 levels were similar in hypox + T4
      and intact + T4 fetuses and increased in both groups relative to their respective
      controls. T4 supplementation restored the lipolytic response to isoproterenol and
      enhanced the response to dibutyryl cyclic AMP at 90 days in hypoxed animals but
      had no effect on basal or stimulated lipolysis in intact fetuses. T4 induced a
      dramatic increase in lipogenesis in hypoxed fetuses when administered during
      either fetal period and produced a slight though significant increase in basal
      lipogenesis in intact fetuses when administered from days 70 to 90 of gestation.
      However, T4 had no effect on basal or insulin-stimulated lipogenesis in intact
      fetuses when administered from days 90 to 105 of gestation. These results
      indicate that T4 may have a primary influence on fetal adipose tissue metabolism
      only in the absence of inhibition from counterregulatory hormones of pituitary
      origin.

PMID- 8260544
TI  - Ovine fetal swallowing and behavioral state responses to sublingual water.
AB  - Ovine fetal swallowing primarily occurs in bouts of activity associated with low
      voltage electrocorticogram activity and breathing movements. Despite similar
      rates of electromyographic swallowing activity, there are significant differences
      in the net esophageal fluid flow among fetuses. To determine if variations in the
      volume of fluids accessible to the fetus (amniotic fluid, lung fluid, salivary
      secretions) affect fetal swallowing, we studied the effects of sublingual
      distilled water infusions on ovine fetal swallowing rates and esophageal flow.
      Seven pregnant ewes at 127 +/- 2 days gestation were chronically instrumented
      with maternal and fetal vascular catheters, fetal electrocortical, electro-ocular
      and electromyograph electrodes, an esophageal flow probe and a sublingual
      infusion catheter. Following a 2-hour control period, consecutive sublingual
      infusions of room temperature distilled water (10 and 20 ml/kg/h) were
      administered for 2 h each. In response to sublingual infusions, fetal plasma
      sodium (142.5 +/- 0.5 to 140.8 +/- 0.8 mEq/l), chloride concentrations (109.2 +/-
      0.4 to 107.7 +/- 0.7 mEq/l) and osmolality (302 +/- 2 to 298 +/- 2 mOsm/kg)
      decreased significantly. Swallowing activity and esophageal flow did not change
      significantly from basal values (47 +/- 9 swallows/h, 19.2 +/- 4.2 ml/h) during
      the sublingual infusions. However, fetal low-voltage electrocortical activity
      increased significantly during both infusion periods (42 +/- 3 to 56 +/- 6%).
      Sublingual distilled water infusion decreases fetal plasma osmolality and alters
      fetal behavioral state without affecting swallowing frequency or esophageal flow.

PMID- 8260545
TI  - Changes in plasma levels of oxygen radical scavenging enzymes during
      extracorporeal membrane oxygenation in a lamb model.
AB  - We studied levels of superoxide dismutase, glutathione, reductase, glutathione
      peroxidase and lipoperoxides in 12 healthy lambs below 1 year of age (8-19 kg)
      under therapy with extracorporeal membrane oxygenation (ECMO). Plasma levels of
      these free oxygen radical scavenging enzymes and lipoperoxides were taken 1 day
      before the ECMO experiment, at the beginning of ECMO after the first rotations of
      the roller pump, during, and after ECMO. The pre-ECMO results of days 1 and 2
      were compared with the during-ECMO results and those with the post-ECMO results
      using the t test for paired samples. We found a significant decrease of both
      superoxide dismutase and glutathione reductase on ECMO, a trend to increased
      lipoperoxide levels, and unchanged levels of glutathione peroxidase. After
      discontinuing bypass the levels began to normalize again. We conclude that ECMO
      reduces some oxygen radical scavenging enzyme levels and exhibits a trend to
      increased lipoperoxide levels. Near total lung collapse with consecutive
      reperfusion injury might be harmful considering these results. However, the
      nonsignificant increase in lipoperoxide levels excludes considerable oxygen
      toxicity during this short ECMO trial.

PMID- 8260546
TI  - Effect of hypoxemia and hypovolemia on retinal and choroidal blood flow in the
      newborn piglet.
AB  - The effect of hypoxemia and/or hypovolemia on ocular blood flow was studied in
      paralyzed and mechanically ventilated newborn piglets with the isotope-labelled
      microsphere method. Twenty-six piglets were studied in four different groups. One
      group of piglets (n = 6) was made hypoxemic by breathing 10% O2, a second group
      (n = 7) and a third group (n = 7) were studied during hypoxemia (10% O2),
      followed by hypovolemia (bleeding 20 and 30% of estimated blood volume,
      respectively). A fourth group of piglets (n = 6) was made hypovolemic by bleeding
      20% of estimated blood volume. Hypoxemia resulted in a 2- to 3-fold increase in
      retinal blood flow (RBF), while hypovolemia did not change RBF, not even when
      preceded by a period of hypoxemia. In the case of choroidal blood flow (ChBF),
      the increase caused by hypoxemia was only 10-40%. Although ChBF decreased
      significantly during hypovolemia, no significant correlation between mean
      arterial blood pressure and ChBF was found. The results indicate that
      autoregulation is normally seen in RBF, but probably not in ChBF. However, during
      hypoxemia autoregulation was found neither in RBF nor in ChBF.

PMID- 8260547
TI  - Thyroidal regulation of lingual lipase development in suckling rats.
AB  - Rat lingual lipase undergoes maturational increases during postnatal development.
      The role of thyroxine (T4) in the control of lingual lipase during development
      was evaluated. T4 given at an early suckling stage (starting day 4 or 5)
      moderately increased lingual lipase (20-30%) compared to age-matched controls. A
      similar dose of T4 given later (age > 2 weeks) was ineffective. The T4-sensitive
      period coincides with a time of low circulating T4, suggesting a role of T4 in
      modulating the development of lingual lipase in rat pups. Since simultaneous
      treatment with U486, a type II glucocorticoid receptor antagonist only partially
      blocked the T4 induction of lingual lipase, T4 appeared to have a direct action
      on the lingual gland. Pups of propylthiouracil (PTU)-treated dams (previously
      found to be hypothyroid) showed a delay in the maturation of lingual lipase
      compared to age-matched pups whose dam was not given PTU. Pups were most
      sensitive to PTU in the early suckling stage. PTU-induced delayed maturation of
      lingual lipase was a result of hypothyroidism, since T4 replacement when given
      early (at the age of 5 days) abolished most of the effect of PTU. When T4 was
      given later (at the age of 10 days), recovery was much less. This suggests the
      presence of an early period that is critically dependent on T4 for the full
      expression of lingual lipase in the rat tongue serous glands.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8260548
TI  - Gestational age correlates with skin reflectance in newborn infants of 24-42
      weeks gestation.
AB  - Accurate gestational age determination is limited in very low birthweight infants
      using neurological and physical assessments. As one of the markers of
      intrauterine development, skin maturation is assessed qualitatively by
      pediatricians. Based on this observation, we hypothesize that skin reflectance
      relates directly to gestational age. Light was delivered and collected from the
      skin through a topically placed optical patch. Reflected light was detected by
      the spectrophotometer and corrected by an adjacent laptop computer to yield the
      true total diffuse reflectance as a function of wavelength between 380-820 nm.
      The calculated reflectance at 837 nm (R837) where it is independent of melanin,
      was determined by extrapolation from the reflectance at 650 and 750 nm. Sixty
      four neonates of different races with gestational ages of 24-42 weeks were
      studied at 2-151 h of age. R837 was related exponentially to gestational age (GA)
      by the equation R837 = Rmax(1-exp[-(GA-G0)/tau]), where Rmax is the maximal value
      of R837, G0 is an apparent delay time before dermal scattering increases rapidly,
      and tau is a time constant, r = 0.88, p < 0.001. In summary, the extrapolated
      skin reflectance offers a quantitative and objective assessment of gestational
      age which is independent of melanin and sex.

PMID- 8260549
TI  - Effects of intrauterine growth on intestinal length in the human fetus.
AB  - Standards for human fetal intestinal length are not well established but have
      important implications for the care of the preterm and intra-uterine growth
      retarded (IUGR) infant. Our purpose was to examine the relationship between intra
      uterine growth and intestinal length in the human fetus. One hundred infants were
      studied. Birth weight and gestational age ranged from 76 to 4,385 g and from 12
      to 42 weeks, respectively. Twenty-one infants were noted to be IUGR. Intestinal
      length (total, small, large) increased (p < 0.0001) with birth weight,
      gestational age, and crown-heel length but was reduced in IUGR infants. The ratio
      of body weight to intestinal length increased with gestation but was also reduced
      in IUGR infants. In conclusion, a reduced functional mass, as suggested by
      decreased intestinal length or body weight:intestinal length ratio, may
      contribute to the poor weight sometimes seen in the very-low-birth weight or IUGR
      infant.

PMID- 8260550
TI  - Catecholamine response at birth in preterm newborns.
AB  - We compared the extrauterine adaptation of preterm with term newborn infants, by
      sequentially measuring plasma catecholamine (CAT) levels at birth and during the
      first 24 h of life. Twenty-seven preterm appropriate-for-gestational-age (AGA)
      infants, less than 35 weeks gestation, were compared with 26 healthy near-term
      AGA infants. Modes of delivery and umbilical arterial pH (mean 7.28) did not
      differ. Infants with asphyxia, presumed sepsis or hypoglycemia were excluded. CAT
      (norepinephrine, epinephrine, dopamine) levels were measured by radioenzymatic
      assay in blood samples from maternal vein, cord vein, cord artery and blood
      samples obtained at 1, 2 and 24 h of postnatal age. At birth, the cord arterial
      CAT levels were significantly higher than maternal venous CAT levels in both
      groups of neonates. Plasma epinephrine levels (mean +/- SD) at 1 and 2 h of
      postnatal age were significantly higher in preterm than in near-term newborns
      (0.98 +/- 0.82 nmol/l vs. 0.30 +/- 0.21 nmol/l at 1 h; 0.98 +/- 0.68 nmol/l vs.
      0.28 +/- 0.29 nmol/l at 2 h; p < 0.05). The norepinephrine and dopamine
      measurements did not differ between the two groups studied at birth, 1, 2 and 24
      h of postnatal age. These data indicate that the preterm infants (25-35 weeks
      gestation) are capable of mounting a catecholamine response at birth similar to
      near-term newborns. The persistent elevation of epinephrine in preterm infants at
      1 and 2 h of life may be attributed to either slower clearance of epinephrine or
      continued stimulation during clinical care in the NICU.

PMID- 8260551
TI  - Increase in plasma platelet-activating factor levels in enterally fed preterm
      infants.
AB  - Because platelet-activating factor (PAF) has been implicated in the pathogenesis
      of neonatal necrotizing enterocolitis (NEC), we designed a prospective study to
      examine plasma PAF levels during the first 14 days of feeding in a population of
      neonates of less than 32 weeks gestation. We found that significantly more
      patients had detectable plasma PAF levels on days 3 and 14 of feeding when
      compared to their prefeeding levels (7% on day 0 vs. 26% at day 3, p = 0.04; none
      on day 0 vs. 18.5% at day 14, p = 0.01). This finding could not be explained by
      decreased plasma activity of acetylhydrolase, the PAF breakdown enzyme,
      spontaneous endotoxinemia or a maturational effect. None of the infants who
      developed detectable PAF levels after feedings were begun went on to develop NEC.
      We conclude that our findings may reflect increased intestinal PAF production
      with the provision of feedings to some premature infants. However, this
      phenomenon by itself does not appear to be a sufficient condition for the
      subsequent development of NEC.

PMID- 8260552
TI  - Measurement of lumbar spinal bone mineral density in preterm infants by dual
      energy X-ray absorptiometry.
AB  - Lumbar spinal bone mineral density (BMD) was measured in 40 preterm infants by
      dual-energy X-ray absorptiometry (DXA). During the first several months of life,
      their BMD was considerably lower than that of normal term infants and the
      osteopenia was more pronounced in the more preterm and smaller infants. Weak
      (inverse) correlations were found between the BMD and urinary calcium/creatinine
      or tubular phosphorus reabsorption ratio. Rickets-like changes in the forearm
      bones did not predict the greater spinal osteopenia. Follow-up study was
      performed in 10 preterms. In 3 of the 4 who underwent the last DXA between 8 and
      12 months, BMD had improved remarkably. Our present study shows the potential of
      DXA for the assessment and management of osteopenia of prematurity.

PMID- 8260553
TI  - Cerebral hemodynamics and oxygenation in preterm infants after low-vs. high-dose
      surfactant replacement therapy.
AB  - In thirteen preterm infants receiving surfactant (Curosurf) replacement therapy,
      changes in cerebral hemodynamics and oxygenation were investigated by near
      infrared spectroscopy. Surfactant instillation led to an instantaneous increase
      in cerebral blood volume (CBV) in all infants, which was primarily due to an
      increase in deoxygenated hemoglobin. Five infants received a low dose (100 mg/kg
      = 1.25 ml/kg) of surfactant and 8 a high dose (200 mg/kg = 2.50 ml/kg). A
      significantly larger increase in CBV was observed in the infants receiving a high
      dose compared to those receiving a low dose of surfactant. We conclude that
      cerebral perfusion is affected more after the instillation of a high dose
      compared to a low dose of surfactant.

PMID- 8260554
TI  - Influence of NaCl supplementation on vasopressin secretion and water excretion in
      premature infants.
AB  - The study was carried out to assess the possible involvement of excess AVP and
      free water retention in the development of late hyponatremia by comparing the
      postnatal course of plasma AVP and urinary excretion of AVP and sodium as well as
      creatinine, osmolar and free water clearances in premature infants with (group S)
      and without (group NS) NaCl supplementation. Plasma total protein and albumin
      concentrations were also determined. Group NS consisted of 8 infants with a birth
      weight of 1,150-1,730 g (mean: 1,440 g) and gestational age of 28-32 weeks (mean:
      30.4 weeks). Group S included 8 infants with a mean birth weight of 1,390 g
      (range: 980-1,700 g) and a mean gestational age of 30.1 weeks (range: 27-32
      weeks). Measurements were made on the 7th day and weekly thereafter until the 5th
      week of life. NaCl supplementation was given in a dose of 3-5 and 1.5-2.5
      mmol/kg/day for 8-21 and 22-35 days, respectively. Infants receiving sodium
      supplements had significantly greater urinary sodium excretion (p < 0.01),
      retained more sodium (p < 0.01), maintained plasma sodium at normal levels and
      gained weight at slightly higher rates when compared with those on low sodium.
      Plasma AVP tended to be higher in group S but did not differ significantly from
      that in NS group. Urinary AVP excretion, however, either expressed in ng/day or
      ng/100 ml GFR, was significantly higher in group S, although the age-related
      increase could not be seen when correction was made for GFR.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8260555
TI  - Changes in static and dynamic skin fold measurements in the first 60 hours of
      life: higher values following cesarean delivery.
AB  - Infants born by cesarean section (CS) have been reported to have increased
      intracellular and total body water and have a slower postnatal decline in cell
      water content compared to vaginally delivered infants. These findings support the
      hypothesis that delivery-related changes in water compartmentalization will
      result in postnatal differences in tissue compressibility. In order to test this
      hypothesis, static and dynamic skin fold thicknesses (SFTs) were obtained in 60
      healthy, term, appropriate for gestational age infants between 1 and 60 h of
      life. Thirty infants were delivered vaginally and 30 by CS. Midtriceps,
      subscapular and abdominal skin folds were measured twice daily during the first 3
      days of life. There were no differences between groups in birth weight, length,
      head circumference, gestational age, sex or ponderal index. Our results showed
      that static SFTs were significantly greater in CS than in vaginally delivered
      infants at birth and remained so throughout the study period. In both groups,
      static SFTs increased while weight decreased over time. At birth, dynamic SFTs
      were significantly greater in infants delivered by CS. We speculate that skin
      fold differences between CS and vaginal deliveries may reflect a different
      dynamic of perinatal body water distribution. The mechanism underlying the
      paradoxical increase in static SFTs in both groups is unknown.

PMID- 8260556
TI  - Resuscitation of the very immature infant: cerebral Doppler flow velocities in
      the first 20 minutes of life.
AB  - Blood flow velocity of the anterior cerebral artery was investigated by Doppler
      ultrasonography in five time intervals up to 20 min after birth in 16 non
      asphyxiated very immature infants (median birth weight 1,058 g, range 720-1,930
      g; median gestational age 30 weeks, range 27-32 weeks) delivered by caesarean
      section and intubated after birth. Heart frequency, oscillometric mean arterial
      blood pressure and blood gases were recorded as well. There was a transitory
      increase in both systolic and end-diastolic velocities (from 29 to 35 and from 1
      to 10 cm/s) during the first 5 min after birth which occurred together with an
      increase in heart frequency. The overall incidence of intracranial haemorrhage
      was low (3/16, 19%). This observation study shows a transitory increase in
      cerebral blood flow velocity with a peak at about 5 min after birth in preterm
      infants < 33 weeks of gestation undergoing standard resuscitation.

PMID- 8260557
TI  - Insulin reduces basal release of atrial natriuretic factor by isolated, perfused
      neonatal pig hearts.
AB  - Plasma atrial natriuretic factor (ANF) levels are markedly altered in diabetic
      rodents suggesting that insulin might be a modulator of ANF release. Effects of
      insulin (25 mU/ml) on basal (nonstimulated) immunoreactive (ir)-ANF release by
      isolated neonatal pig hearts paced at 150 beats/min and perfused with no change
      in atrial stretch were examined. Release of ir-ANF decreased with age from 1-3
      days postpartum (146.0 +/- 38.4 to 62.2 +/- 20.5 fmol/g/min). Insulin stimulated
      myocardial glucose utilization and lactate production approximately 2-fold, but
      uniformly decreased ir-ANF release by approximately 25%, regardless of age.
      Correlations between ir-ANF release and myocardial metabolism suggest independent
      influences of insulin on these two events. In addition, it appears that this
      model might be reasonably exploited to investigate episodic ANF release and its
      regulation during ontogeny and in a variety of physiological states.

PMID- 8260558
TI  - The neonatal guinea pig as a model for human galactose metabolism: galactose-1
      phosphate uridyltransferase activity.
AB  - The specific activity of galactose-1-phosphate uridyltransferase was measured in
      fetal and neonatal guinea pig liver during the first 10 days of age. Activity was
      approximately six times greater than in adult animals, and peaked during the
      first 48 h after birth. Activity dropped sharply during the next 2 days, followed
      by a gradual decline. Liver galactose and glycogen levels were stable throughout
      the study period. Liver glucose rose significantly after birth, then dropped
      slightly. The pattern of uridyltransferase in the guinea pig is similar to that
      reported for phosphoenolpyruvate carboxylkinase and pyruvate carboxylase.
      Compared to the rat, specific activity of uridyltransferase peaked earlier,
      possibly due to the guinea pig's advanced maturity.

PMID- 8260559
TI  - Effect of preclosure colostrum intake on the development of the intestinal
      epithelium of artificially reared piglets.
AB  - Trophic factors in mammalian colostrum promote the growth of the small intestine
      of neonates. To investigate the effect of colostrum feeding on the expression of
      specific intestinal proteins, animals were reared in a minimal disease unit and
      fed either sow colostrum or a commercial substitute by gastric intubation at 3
      hour intervals over the first 24 h of life. Animals were then reared on a
      commercial milk replacer and fed over a maximum period of 5 weeks. Intestinal
      protein, DNA and histology data suggested a positive effect of colostrum on
      intestinal growth in the initial postnatal period. At week 1 post partum
      intestinal lactase was found to decline significantly in colostrum-fed (CF)
      piglets compared to substitute-fed animals. This effect was no longer apparent at
      3 and 5 weeks post partum. Sucrase activity was significantly greater in CF
      piglets and this effect was sustained during the 5 postpartum weeks studied. The
      changes in enzyme activity could be correlated with posttranslational sialylation
      of intestinal membranes. These result suggest that feeding colostrum enhances the
      maturational decline in lactase activity and the expression of sucrase activity.
      The role of glycosylation of enzyme proteins in relation to their biological
      activity is discussed.

PMID- 8260560
TI  - Early life environmental deterioration, nutrition and ontogenesis of the motor
      cortex in the rat: a Golgi study.
AB  - Sprague-Dawley albino rats were subjected to an experimental paradigm in which
      environmental and nutritional variables were studied from birth to day 18. The
      use of Golgi-Cox-Sholl methodology allowed quantitative evaluations of neurons
      which were randomly impregnated with metallic mercury after fixation in a mercury
      salt. The nutritional treatment employed did not significantly influence the
      cytoplasmatic differentiation of cortical neurons although it was able to induce
      gross morphological modifications in body weight and size. By contrast, an
      impoverished surrounding during a limited period of time had a profound effect on
      the basal dendritic tree. The evidence presented here suggests the importance of
      the preweaning environment on the development of neural appendages. Motor
      pyramids of pups housed in deteriorated conditions underwent a progressive
      decrement in the length and number of peripheral branches and terminal dendrites.
      A decreased rate of cortical differentiation was also observed in overnourished
      pups as a result of reducing the litter size. This regressive event, can probably
      be attributed to social and sensory-motor limitations of the experimental group.
      However, to confirm this possibility, further research is required.

PMID- 8260561
TI  - The effect of hypocapnia and mechanical pulmonary stress on lung tissue in
      newborn lambs.
AB  - Positive pressure ventilation, using high inspiratory pressures, often causes
      lung damage. When associated with hypocapnia, it can produce severe focal
      alveolar alkalosis and can cause damage in areas of low blood flow. A vein-to
      vein extracorporeal membrane oxygenator (ECMO) system was used to control blood
      gases independently of mechanical ventilation in 12 healthy newborn lambs. After
      connection to the ECMO system, ventilation was started with a peak inspiratory
      pressure of 35 cm H2O and a positive end-expiratory pressure of 5 cm H2O; the
      ventilator rate was 40/min with I:E = 1.5 and FiO2 = 1.0. In 6 of the 12 lambs
      sweep gases through the silicone membrane were regulated to assure arterial
      normocapnia. The other 6 were ventilated with the same settings and perfused with
      the same pump flow, but PaCO2 was allowed to fall to hypocapnic levels. The lambs
      were ventilated for 4 h. Average pH and PaCO2 were 7.62 +/- 0.14 and 2.11 +/-
      0.54 kPa, respectively, in the hypocapnic group and 7.39 +/- 0.11 and 4.79 +/-
      0.51 kPa in the normocapnic group. After sacrificing the lambs, the lungs were
      inspected macroscopically and microscopically by computer-assisted morphometry to
      assess atelectasis and lung edema. Macroscopically there were no hemorrhages,
      barotrauma or widespread atelectasis of the lungs in either group. The thickness
      of interlobular lung septa in the right upper lobe was 32.5 +/- 18.0 microns for
      the hypocapnic group and 29.7 +/- 12.5 microns for the normocapnic group. The
      parenchymal-alveolar area ratio in the right upper lobe was 28.4 +/- 5.04 and
      24.6 +/- 3.75% in the hypocapnic and normocapnic groups, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260562
TI  - Twenty-four hour profiles of glucose, corticosterone and adrenocorticotropic
      hormone during the first postnatal day in rats.
AB  - Soon after birth, mammals are often confronted with the challenges of hypoxia,
      hypothermia and hypoglycemia. The incidence of the latter in the human population
      is roughly 2-20% of all live births. We characterized the glucose profile over
      the first 24 h of postnatal life in a large population of suckling, nonfasted
      rats. Approximately 63% were hypoglycemic (plasma glucose < 60 mg/dl) during the
      first 4 h after birth; from 6 to 24 h after birth this number was reduced to 10%.
      Low glucose levels in the first hours after birth were significantly associated
      with high plasma glucocorticoid and adrenocorticotropic hormone levels.
      Glucocorticoid injections 2 h after birth that elevated plasma corticosterone to
      high physiological levels for 1-2 additional hours significantly increase plasma
      glucose levels compared to vehicle-injected controls. These results suggest that,
      like the human newborn, rat pups are susceptible to developing neonatal
      hypoglycemia with about the same frequency as in babies. Also, the hypothalamic
      pituitary-adrenocortical (HPA) axis appears to be active from birth and may be
      responsive to hypoglycemia stress during this early period (contrary to later
      neonatal ages when the HPA axis is quiescent in rats). Finally, glucocorticoids
      appear to prevent the development of hypoglycemia shortly after birth.

PMID- 8260563
TI  - Changes in event-related potentials with stimulant medication in children with
      attention deficit hyperactivity disorder.
AB  - Thirty-two children with attention deficit hyperactivity disorder (ADHD)
      undergoing a 4 week double-blind medication assessment (methylphenidate) and 32
      normal controls were studied using event-related potentials (ERPs). The ERPs were
      recorded from 13 active electrodes during a visual feature detection task.
      Significant age effects were found in N2, P3a and P3b latencies, that did not
      interact with group. The P3a and P3b latencies were significantly longer in the
      ADHD children on baseline testing; there were no latency differences between the
      groups of children when the normal controls were compared with the ADHD children
      on their optimal drug dosage (as determined by extensive behavioural and
      cognitive assessments). There were no significant distributional effects either
      between groups, or with the ADHD children as a function of medication; there were
      also no significant differences in reaction time measures. Thus, only the ERPs
      reflected slowed processing in the ADHD children that normalized on appropriate
      medication.

PMID- 8260564
TI  - Adrenaline and the relationship between neurosomatism, aerobic fitness and mental
      task performance.
AB  - The influence of neurotic instability as manifested by functional somatic
      complaints (neurosomatism) and aerobic fitness on responses to mental stress and
      to intravenous adrenaline infusions were investigated in 44 university students.
      Adrenaline-induced changes from resting levels in state anxiety and somatic
      anxiety were significantly more pronounced in high than in low neurosomatic
      subjects and all anxiety ratings were generally negatively related to aerobic
      fitness. Cardiovascular reactivity was induced by mental stress and by adrenaline
      infusions, but was not altered by neurosomatism. In individuals assumed to be
      characterized by a susceptibility to adrenergic effects, interference of
      adrenaline-induced arousal with cognitive performance may not occur. In contrast,
      a further increase in performance may occur when adrenaline is infused.
      Performance measures correlated negatively with anxiety during the baseline task
      and the placebo task, but this negative relation was absent during the adrenaline
      infusion and was replaced by positive relations between performance and aerobic
      power. The complex relations between bodily symptoms of anxiety, aerobic fitness
      and mental stress are discussed.

PMID- 8260565
TI  - Event-related potentials to auditory stimuli following transient shifts of
      spatial attention in a Go/Nogo task.
AB  - The effects of spatial attention on the human auditory event-related potential
      (ERP) were examined, while attention was oriented on a trial-by-trial basis.
      Additionally, it was investigated whether the ERP modulation to Nogo stimuli
      depends on attention. In four experiments, Go and Nogo stimuli were delivered
      13.3 degrees from the left or right of fixation. In Experiments 1 and 2, subjects
      had to press a button whenever a Go stimulus was presented at the location
      previously indicated by a visual precue. In Experiments 3 and 4, the cue
      indicated the likely location of the upcoming stimulus but a button-press was
      required to Go stimuli at either location. Attended (correctly cued) as compared
      with unattended (incorrectly cued) stimuli elicited a bimodal negative deflection
      in the ERPs with a parietally distributed first and a frontocentrally distributed
      second part. Further, Nogo stimuli evoked differential ERP modulations in the N2
      and in the P3 range. The former were dependent and the latter were independent of
      spatial attention.

PMID- 8260566
TI  - On dopaminergic modulation of temporal information processing.
AB  - Temporal processing of durations in the range of seconds or more (i.e. time
      estimation) is cognitively mediated, whereas processing of brief durations in the
      range of milliseconds (i.e. time perception) appears to be beyond cognitive
      control and based on neural counting mechanisms. Although there is some evidence
      from animal and human studies suggesting that the internal timing mechanism
      underlying time perception is modulated by the effective level of brain dopamine,
      the findings are not conclusive. Therefore, the effects of pharmacologically
      induced changes in D2 receptor activity on temporal information processing were
      evaluated. In a double-blind design, either 3 mg of haloperidol, 150 mg of
      remoxipride, or placebo were administered in a single oral dose. Performance on
      time estimation was significantly impaired by both haloperidol and remoxipride as
      compared with placebo. Both drugs obviously affected cognitive mechanisms
      underlying temporal processing of durations in the range of seconds. On the other
      hand, only haloperidol produced a significant decrease in performance on time
      perception as compared with placebo and remoxipride, whereas the remoxipride and
      placebo groups did not differ significantly. The differential effects of
      haloperidol and remoxipride on performance on time perception suggest that D2
      receptor activity in the basal ganglia may play a critical role in timing of
      brief durations in the range of milliseconds.

PMID- 8260567
TI  - Uric acid level increases in humans engaged in gambling: a preliminary report.
AB  - The effect of gambling and gaming on plasma levels of uric acid was studied.
      Blood samples were obtained from normal subjects while they gambled for money or
      while they played checkers without betting. There was an interaction of time and
      activity reflecting primarily an association of increased uric acid levels during
      gambling over time, compared with gaming and relaxation. This indicates that
      gambling can increase plasma levels of uric acid.

PMID- 8260568
TI  - The role of the pharmacist in health care reform.

PMID- 8260569
TI  - Community health organizing: whom are we empowering?
AB  - Current strategies for initiating and operating community health programs rely on
      one of two approaches. One is a predetermined, operational process. The other
      comes from the grassroots, beginning with involvement of the recipients of the
      program. This editorial chronicles how one grassroots program, begun by volunteer
      mothers and one community health nurse, developed into a partnership for primary
      health care that advocates and empowers the entire community. In the end, the
      editorial challenges community health organizers to ask whom their programs are
      empowering--the community or the organizers themselves?

PMID- 8260570
TI  - Poverty, residential segregation, and black/white mortality ratios in urban
      areas.
AB  - Researchers speculate that in addition to poverty, residential patterns may
      contribute to black/white differences in mortality rates. But few have assessed
      the relationship. This study reports considerable variation in the black/white
      ratio of age-specific all-cause mortality rates (ages 15-24 to 65-74 years) from
      1982 to 1986 among the 38 U.S. Standard Metropolitan Statistical Areas (SMSAs)
      with populations greater than one million in 1980. The black/white poverty-rate
      ratio for each SMSA was a stronger predictor of variation in the black/white
      mortality ratio for men than for women. For both men and women age 15-44, the
      level of black/white residential segregation was a significant (positive)
      predictor of the black/white ratio of the age-standardized death rate. This
      analysis also identifies SMSAs containing geographic areas with unusually high or
      low black/white mortality ratios, and indicates the need for more-detailed
      studies of explanations for such variation.

PMID- 8260571
TI  - Impact of employment-based health insurance on home attendants.
AB  - This study examines 253 newly hired home attendants to measure the degree to
      which employment-based health insurance can affect health status and utilization
      of health care services among a working poor population that has little
      experience with health insurance and may face other significant barriers to care.
      Physician contacts increased after benefits were received; attendants who had no
      coverage during the prior year experienced the greatest average increase. More
      attendants also reported using emergency rooms. Neither hospitalizations nor
      health status were affected. These findings indicate that insurance benefits may
      substantially improve access to care for many working poor persons, regardless of
      other barriers they may face.

PMID- 8260572
TI  - A health-profile comparison of delinquent and homeless youths.
AB  - Little is known about the health status and health care needs of homeless and
      delinquent youths. This study provides medical data (medical history and physical
      examination) on samples of delinquent (n = 245) and homeless (n = 160) youths in
      San Francisco, CA. Although homeless youths had somewhat more medical problems
      than did delinquent youths, both groups had a multiplicity of medical problems,
      many of which were worse than among the general adolescent population. A
      substantial percentage of both samples did not have adequate health care
      coverage. Medical services to high-risk youths should be improved by providing
      street outreach, public health clinics, and multiservice centers for adolescents.

PMID- 8260573
TI  - In vitro and ex vivo evaluation of methotrexate removal by different sorbents
      haemoperfusion.
AB  - The administration of high doses of Methotrexate (HDMTX) seems to be very
      effective in neoplastic treatment. Furthermore high doses of the drug could
      overcome the Methotrexate (MTX) resistance that it is possible to observe in some
      kind of cancers. To avoid several serious problems in the therapeutical
      application of HDMTX such as nephrotoxicity, hepatotoxicity and the difficulty to
      assess the right therapeutic range of the specific antagonist Leucovorin, a
      Haemoperfusion (HP) treatment could be very usefulL. In this study 3 anion
      exchange resins with different active group (trimethylammonium,
      dimethylethanolammonium and dimethylammina) and a spherical petroleum based
      charcoal were tested both in vitro and ex vivo to evaluate their capability to
      remove MTX. These results show a good strength and biocompatibility of the 4
      sorbents and demonstrate the active group trimethylammonium resin as the most
      effective one.

PMID- 8260574
TI  - Enhanced attachment and growth of human endothelial cells derived from umbilical
      veins on ammonia plasma modified surfaces of PTFE and ePTFE synthetic vascular
      graft biomaterials.
AB  - Ammonia plasma generated by electrical discharge at low pressure was employed for
      the surface modification of PTFE and ePTFE. A new chemistry at the plasma treated
      surfaces is reported. X-ray photoelectron spectroscopy studies showed the
      incorporation of C-N, C-O, C = O etc functional groups on the plasma treated
      surfaces. Human endothelial cells derived from umbilical veins (HUEC) were used
      to seed the plasma treated PTFE and ePTFE surfaces to assess the attachment and
      growth. Enhanced attachment and growth of HUEC was observed on the plasma treated
      surfaces. In addition, the performance of these surfaces in this respect was
      found to be considerably superior to human collagen or human fibronectin or
      collagen-fibronectin coated PTFE. HUEC attachment and growth on these plasma
      treated surfaces was further enhanced by immobilizing collagen or fibronectin or
      collagen-fibronectin. Ammonia plasma treated and untreated ePTFE vascular graft
      samples were seeded with 3.6 X 10(4) cells/sample. At 24 hrs after seeding, HUEC
      cell attachment was studied. Although, HUEC attachment on collagen or fibronectin
      coated ePTFE was improved, but there was no significant difference between the
      number of cells attached to these surfaces when compared with those adhered to
      plasma treated ePTFE without collagen or fibronectin coating. Collagen or
      fibronectin coated plasma treated surfaces showed better performance over their
      respective controls.

PMID- 8260575
TI  - STM of glow-discharge treated surfaces.
AB  - As a model surface, graphite slides were treated by pure nitrogen gas plasma for
      different periods (15 sec-5 min). These samples were kept in air or under argon
      atmosphere in sealed holders. STM images were obtained at constant current mode.
      Results showed that both the number and the size of clusters formed by plasma
      deposition increased with exposure time.

PMID- 8260576
TI  - Evaluation of 90:10 poly(D,L-lactide-co-glycolide) microspheres containing
      norethisterone: drug release and biodegradation.
AB  - Poly(D,L-lactide-co-glycolide) (PLG, 90:10) microspheres containing 20%
      norethisterone (NET) were prepared by solvent evaporation method. Microspheres in
      the size ranges of 65 to 100 microns were sterilized by irradiation and used for
      further study. In vitro release showed fairly constant release of NET from the
      above microspheres over more than 90 days. However, in vivo drug release
      determined by residual NET analysis after i.m. injection in rats indicated a
      faster release rate. About 95% of NET was released in a period of 45 days. At the
      dose of 80 mg of microspheres, vaginal estrus cycles were inhibited for 45 days
      compared to 27 days for the same dose of NET crystals in rats. Biodegradation of
      the microspheres was tested by direct measurement of molecular weight losses and
      SEM observation of morphological changes of the microspheres, which showed
      continuous erosion in the internal matrix of microspheres with the decrease of
      molecular weight of PLG until total collapse of microspheres, and biodegradation
      was faster in rats than in human serum at 37 degrees C in vitro. Total
      degradation of 90:10 PLG microspheres was less than 7 months in rats and more
      than 9 months in vitro.

PMID- 8260577
TI  - Alpha-amylase immobilized on plastic supports: stabilities, pH and temperature
      profiles and kinetic parameters.
AB  - The covalent immobilization of alpha-amylase on new isocyanate, acid chloride and
      carboxylic acid--activated plastic supports shows the viability of such supports
      for immobilizing enzymes, especially those reacting with 1,6-diaminohexane and
      glutaraldehyde for producing side arms. The operational stability of immobilized
      alpha-amylase could be extended by crosslinking the enzyme or by extending the
      support's side arm (substrate concentration has no effect). Inactive immobilized
      alpha-amylase were unfolded and then refolded at elevated temperature, these
      supports were found to be essential in increasing the stability of the enzyme
      during refolding. The pH curves for the immobilized enzyme were in general found
      not to be shifted from the soluble enzyme's pH optimum, although one isocyanate
      plastic support derivative shifted the pH activity profile of alpha-amylase to a
      higher range by 1.5 pH units, probably due to reaction between the enzyme and the
      free anhydride groups existing on the support's surface. In all cases, the
      immobilized enzyme's temperature activity profiles were shifted to a lower
      temperature range when compared to the soluble enzyme. The immobilized alpha
      amylase Michaelis constants increased and the the maximum rates and specific
      activities decreased when compared to the soluble enzyme kinetic parameters.

PMID- 8260578
TI  - Preparation of heat responding artificial cells.
AB  - Enzyme-loaded microcapsules were prepared and treated with
      dimyristoylphosphatidylcholine molecules so as to control the permeation of
      substrates through the microcapsule membranes. The activities of enclosed enzymes
      increased with increase in ambient temperature, but gave an abrupt change at
      around the phase transition temperature of the lipid. The experimental results
      indicate the possibility of making artificial cells which respond to the
      temperature change of the surrounding medium.

PMID- 8260579
TI  - Systemic hemodynamic and hepatic microvascular responses to a 33% blood volume
      exchange with whole blood, stroma-free hemoglobin, and oxypolyhemoglobin
      solutions.
AB  - Little is known about the microvascular effects of blood replacement solutions.
      This study was undertaken to develop an animal model suitable for studies of the
      microcirculatory effects of such solutions and to investigate microvascular
      responses to isovolemic transfusion with stroma-free hemoglobin (SFH), whole
      donor blood, or a new potential blood substitute solution containing
      oxypolyhemoglobin (OPH) as an oxygen carrier. Hamster livers were exposed and the
      microcirculation studied using intravital epifluorescent video microscopy. 33%
      blood volume replacement with SFH elevated systemic blood pressure by 25 Torr.
      Accompanying this increase in pressure was a 36% decrease in sinusoidal blood
      flow velocity and a 10% decrease in terminal hepatic venular diameters. Terminal
      portal venular diameters did not change. Decrease in liver sinusoidal perfusion
      was not due to neutrophil mediated injury, as myeloperoxidase activity in
      jejunum, liver, kidney, and lung remained unchanged. The reduction in perfusion
      was likely due to systemic vasoconstriction produced by SFH. In contrast,
      transfusion with whole blood did not change any of the measured parameters
      showing the excellent stability of the model. OPH transfused animals exhibited
      only a small 10 Torr transient increase in MAP 15 min post-transfusion. By 30 min
      MAP returned to the pre-infusion value. No significant changes were observed in
      either venular diameters or sinusoidal velocities in this group of animals. These
      results demonstrate suitability of this model for studies of the microcirculatory
      and hemodynamic effects of blood replacement solutions. Furthermore, OPH solution
      produced only minor transient disturbances in microvascular and systemic
      parameters.

PMID- 8260580
TI  - Association of polyacrylamide beads to polyethylene terephthalate prostheses.
AB  - A method for the coupling of polyacrylamide beads to polyethylene terephthalate
      (PET) vascular prostheses is described. The reactional procedure used is
      performed along several steps; acrylic acid grafting on PET textile fibres, in
      order to introduce reactive carboxylic groups, introduction of terminal primary
      amine groups onto the beads, and then, attachment method which consists in
      coupling carboxylic groups of prostheses with amine groups of modified beads. The
      relative weight increase of the samples before and after the coupling reaction
      and, microscopic observations of beads distribution onto the prostheses surface
      demonstrate the binding feasibility of polyacrylamide matrices to PET prostheses.
      In the near future, authors expect to replace these beads by microcapsules with
      polyacrylamide wall and containing active compounds to improve the vascular
      prostheses biocompatibility.

PMID- 8260581
TI  - Immobilization of aminoacylase in polyethyleneimine stabilized calcium alginate
      beads for L-phenylalanine production.
AB  - Aminoacylase I (E.C.3.5.1.14) was immobilized by entrapment in calcium alginate
      beads coated with polyethyleneimine for the production of L-phenylalanine by the
      hydrolysis of a racemic mixture of N-acetyl-DL-phenylalanine. The operational
      stability in terms of batch operation and continuous reaction in packed-bed
      bioreactor were studied. Kinetic constants, Km and Vmax values of free and
      immobilized enzymes were studied. Polyethyleneimine treatment was found to
      enhance the operational stability of the enzyme though its activity was
      substantially reduced. When polyethyleneimine-coated calcium alginate beads were
      packed into packed bed bioreactor, it was stable for at least 25 days under
      continuous operation without appreciable loss of activity.

PMID- 8260582
TI  - Synthesis and interactions with blood of polyetherurethaneurea/polypeptide block
      copolymers.
AB  - Polyurethane/polypeptide block copolymers were synthesized. Infrared spectroscopy
      and differential scanning calorimetry revealed that in the block copolymers both
      segments undergo phase-mixing, while in polyurethane/polypeptide blend both
      components undergo phase-separation. Contact angle measurement showed that in the
      block copolymers polyurethane segments tended to appear on the membrane surface,
      whereas in polyurethane/polypeptide blend polypeptide components appeared on the
      membrane surface. In vitro nonthrombogenicity of the block copolymers was similar
      to that of homopolymers or polymer blends, though adhesion and deformation of
      platelets were suppressed on the block copolymer membranes.

PMID- 8260583
TI  - [European network for quality assurance in nursing].

PMID- 8260584
TI  - [Scientific investigation on the development of nursing science].

PMID- 8260585
TI  - [Pathways to the development of a nursing science able to be integrated into
      practice].

PMID- 8260586
TI  - [Leininger's theory of cultural nursing diversity and universality].

PMID- 8260587
TI  - [Nursing of patients from foreign cultures].

PMID- 8260588
TI  - [Patient oriented development of theories as a basis for the teaching of
      nursing].

PMID- 8260589
TI  - [Means of the production of knowledge in nursing--didactic developments in the
      profession].

PMID- 8260590
TI  - [Structure model of practical instruction. 1].

PMID- 8260591
TI  - [Nursing models and teaching practice. 1].

PMID- 8260592
TI  - The role of interleukin-6 in lipopolysaccharide-induced weight loss, hypoglycemia
      and fibrinogen production, in vivo.
AB  - It was recently shown that interleukin (IL)-6 is an important mediator involved
      in the Colon (C)-26 model of experimental cancer cachexia. In this study, we
      wished to determine whether IL-6 is also involved in several metabolic changes
      associated with lipopolysaccharide (LPS) challenge. Administration of a
      relatively high amount of LPS to mice induced a transient weight loss,
      hypoglycemia, hypertriglyceridemia and an increase in the hepatic acute phase
      reactant, fibrinogen. Pretreatment of mice with the rat anti-murine IL-6 antibody
      (20F3), but not with a control antibody, resulted in a significant improvement of
      LPS-induced hypoglycemia and weight loss as well as a significant decrease of
      plasma fibrinogen. Anti-IL-6 antibody had no effect on LPS-induced
      hypertriglyceridemia. On the other hand, the pretreatment of mice with anti
      murine TNF (TN3.19) antibody was able to completely inhibit elevation of
      triglycerides and modestly improve LPS-induced weight loss although it had no
      effect on hypoglycemia and fibrinogen production. Taken together, these results
      suggest that IL-6 plays a role in some of the metabolic changes associated with
      both an acute (i.e. LPS challenge) and chronic (C-26 cachexia) inflammatory
      conditions.

PMID- 8260593
TI  - Glycosylation does not affect in-vitro biological activity of interleukin-3.
AB  - Murine interleukin-3 is secreted by activated T cells in three major molecular
      mass classes, which differ from one another in the extent of their N-linked
      glycosylation. Experiments were performed to determine whether carbohydrate
      content of different IL-3 glycoforms will affect their biological activity. IL-3
      produced by activated T cells was biosynthetically labeled with 35S-methionine
      and the three major IL-3 glycoforms forms, with M(r) values of 22,000, 28,000 and
      36,000, were purified using antibody affinity chromatography and preparative SDS
      PAGE. Portions of these IL-3 glycoforms were enzymatically deglycosylated with N
      glycanase and the bioactivity of each IL-3 glycoform and the corresponding
      deglycosylated fraction was compared in cell proliferation assays. The amount of
      35S-label present in the samples was used as an index of protein amount so that
      equivalent concentrations of the various IL-3 forms could be compared. Our
      results indicate that the three major glycoforms have identical specific activity
      and that removal of N-linked carbohydrate does not change the specific in-vitro
      activity of IL-3. In addition to the three major glycoforms, small amounts of non
      glycosylated IL-3 were also recovered from the affinity purified T-cell derived
      material. Using again the level of incorporated 35S as reference point, no
      difference in bioactivity compared with glycosylated IL-3 was detected. There is
      potential heterogeneity in IL-3 receptor complexes present on the many different
      cell types responsive to IL-3. We therefore tested whether the three IL-3
      glycoforms differed in their interaction with various IL-3 responsive cell
      lines.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260594
TI  - Elevated levels of TNF in the joints of adjuvant arthritic rats.
AB  - The primary purpose of this study was to determine whether local levels of tumor
      necrosis factor (TNF) were elevated in chronically inflamed joints in rats with
      adjuvant-induced arthritis (AA). We also wished to develop methodology for the
      quantitative measurement of joint TNF, and to examine the effects of known anti
      inflammatory agents on joint TNF levels. TNF levels were measured in joints from
      AA rats taken during the systemic phase (day 20) of arthritic disease. Using the
      L929 bioassay, joint extracts from AA rats had significantly greater TNF levels
      (1054 +/- 147 pg/g tissue) than joint extracts from normal rats (110 +/- 42 pg/g
      tissue). Administration of ibuprofen failed to significantly inhibit TNF levels
      in the joint at a time point when paw swelling was significantly reduced. The
      immunomodulating agents, methotrexate, cyclosporin A (CSA) and HWA486 profoundly
      inhibited both joint TNF levels and paw swelling. The specificity of this assay
      for TNF was supported by studies with a polyclonal rabbit anti-mouse TNF antibody
      which neutralized 78-87% of the TNF activity in the joint extracts. Our studies
      demonstrate a quantitative increase in local TNF expression in adjuvant arthritis
      and support a role for TNF in chronic inflammation.

PMID- 8260595
TI  - Detection and localization of HIV RNA and TNF mRNA in rectal biopsies from
      patients with AIDS.
AB  - The objective of this study was to compare the localization of cells containing
      human immunodeficiency virus (HIV) RNA and tumor necrosis factor (TNF)-alpha mRNA
      in rectal mucosa by RNA in-situ hybridization in a retrospective analysis of
      archived rectal biopsy specimens. RNA in-situ hybridization studies were
      performed in 27 HIV-seropositive individuals and seven controls, using antisense
      and sense 35S-labeled riboprobes. The detection and localization of positive
      cells were compared. HIV was RNA detected in 44% of biopsies, while TNF-alpha
      mRNA detected in 22%. TNF mRNA was found in biopsies from patients with and
      without opportunistic infections. All cells expressing TNF-alpha mRNA and most of
      the cells expressing HIV RNA were found in close proximity to the epithelial
      surface. The content of an HIV-associated protein, p24, in mucosal homogenates,
      determined by a quantitative ELISA technique was significantly higher in the
      subgroup of patients with positive in situ hybridization studies for TNF-alpha
      mRNA than in the subgroup with negative studies. The colocalization of TNF-alpha
      mRNA and HIV RNA immediately beneath the epithelium suggests a specific
      relationship between them, as well as a possible relationship to a luminal
      factor.

PMID- 8260596
TI  - Production of colony-stimulating factor 1 by T cells: possible involvement in
      their interaction with antigen-presenting cells.
AB  - Colony-stimulating factor 1 (CSF-1) is required for the growth and
      differentiation of mononuclear phagocytes, and is also involved in modulating
      various activities in mature cells. We report herein that T-cell lines produce
      4.6 and 1.5 kb mRNA species of CSF-1, and express the CSF-1 protein on their
      outer membranes, as determined by immunofluorescence staining with anti-CSF-1
      antibodies. The CSF-1 protein is biologically active. Interested by the possible
      immunoregulatory function of CSF-1, we assessed its effect in an assay of antigen
      presentation to the T cell lines. We found that anti-CSF-1 antibodies inhibited T
      cell stimulation. Moreover, soluble CSF-1 could not overcome this inhibition, but
      exerted a significant inhibitory activity on the interaction between T cells and
      antigen-presenting cells leading to T-cell activation and proliferation in vitro.
      Based on these observations we propose that T-cell CSF-1 may be involved in the
      interaction of these cells with CSF-1 receptor bearing antigen-presenting cells.

PMID- 8260597
TI  - The mouse C-reactive protein (CRP) gene is expressed in response to IL-1 but not
      IL-6.
AB  - C-Reactive protein (CRP) is a minor acute phase reactant (APR) in the mouse,
      whereas CRP is the prototypical and one of the major positive APRs in all other
      mammals. MoCRP gene expression was tissue specific for the liver and induced by
      culture supernatants of LPS-activated macrophages. MoCRP gene expression by
      isolated hepatocytes in culture increased c, 3-fold in response to interleukin
      (IL)-1, but not IL-6. IL-6 is the most potent inflammatory cytokine for the
      induction of human CRP and many other APRs. By contrast, gene expression of the
      major APR of the mouse, serum amyloid P-component (SAP), a structural homologue
      of CRP, increased in response to either IL-1 or IL-6 under the same conditions.
      The region containing two potentially IL-1 responsive C/EBP elements in the moCRP
      gene failed to respond to IL-1 when a pCAT construct containing the elements was
      transfected into Hep 3B2 hepatoma cells. Therefore, IL-1 may influence the
      expression of the moCRP gene at the post-transcriptional rather than at the
      transcriptional level. The findings suggest that moCRP may be a minor APR because
      of the limited response of the gene to inflammatory cytokine signals.

PMID- 8260598
TI  - Regulation of IL-1 gene expression: differential responsiveness of murine
      macrophage lines.
AB  - In order to begin to define the mechanisms by which lipopolysaccharide (LPS)
      regulates IL-1 gene expression, we have examined IL-1 RNA levels, the
      transcription rate of the IL-1 genes, and IL-1 mRNA stabilities in P388D1/C,
      RAW264.7, and murine peritoneal exudate cells (PEC). These experiments showed
      that total cellular IL-1 RNA levels and IL-1 transcription rates were
      dramatically upregulated in all three cell types. In all cases, IL-1 alpha and IL
      1 beta cellular RNA levels and gene transcription rates were regulated in
      parallel. However, the profiles of IL-1 gene activation during the 24 h after LPS
      treatment differed in these three cell types. Additionally, culture in the
      presence of actinomycin D (Act D) showed differential stabilities of the IL-1
      alpha and IL-1 beta RNAs in these cells. In peritoneal exudate cells, the half
      lives (t1/2) of the IL-1 alpha and IL-1 beta RNAs were each > 8 h. In RAW264.7
      cells, the stability of the IL-1 beta RNA was greater than the IL-1 alpha RNA
      (t1/2 > 8 h and approximately 6 h, respectively). In P388D1/C cells, the t1/2's
      of the IL-1 alpha and beta RNAs varied depending on the time of addition of
      actinomycin D. This and other data suggest that components of the IL-1 RNA
      catabolic pathway are labile and sensitive to treatment with actinomycin D.
      Together these data indicate that the two IL-1 genes show a diverse regulatory
      repertoire, even within related mononuclear phagocytic cells.

PMID- 8260599
TI  - Cloning and characterization of the tandemly arranged bovine lymphotoxin and
      tumour necrosis factor-alpha genes.
AB  - The screening of a bovine genomic library with a human tumour necrosis factor
      alpha (TNF-alpha) cDNA probe resulted in the isolation of a 7.2 kb DNA fragment
      containing the entire bovine TNF-alpha gene. Analysis of this genomic clone
      showed that it also contains the bovine lymphotoxin (LT, TNF-beta) gene.
      Comparison to published sequences of human, murine, ovine and rabbit counterparts
      allowed us to delineate the coding sequences, the promoters and the enhancers of
      these two genes. Sequences involved in the regulation of translation and in the
      mRNA stability were found in the 3' untranslated regions.

PMID- 8260600
TI  - Tumour necrosis factor-alpha enhances cAMP-induced programmed cell death in mouse
      thymocytes.
AB  - During T-lymphocyte differentiation in the thymus, the majority of thymocytes die
      by apoptosis in situ. This process is characterized by internucleosomal DNA
      fragmentation and is induced by a number of stimuli including glucocorticoids,
      calcium ionophore, cAMP and 12-o-tetradecanoylphorbol 13-acetate (TPA). In this
      study, the effect of cytokines tumour necrosis factor-alpha (TNF-alpha) and
      interferon gamma (IFN-gamma) on the programmed cell death of thymocytes was
      examined by measuring DNA fragmentation and LDH release. TNF-alpha and IFN-gamma
      had no effect on DNA fragmentation in control and TPA, or A23187-treated
      thymocytes. Both human and murine rTNF-alpha enhanced cAMP-induced programmed
      cell death dose-dependently, but IFN-gamma had no effect on the process. TNF
      alpha did not stimulate cAMP accumulation in control or 2-chloroadenosine-treated
      thymocytes. TPA markedly stimulated cAMP-induced DNA fragmentation as a result of
      6 h incubation, whereas TNF-alpha did not. Thus TNF-alpha did not appear to
      activate protein kinase C directly. The effect of TNF-alpha was observed in the
      cell preparations from which adherent cells had been removed, suggesting that
      cytokines secreted by adherent cells in response to TNF-alpha are not involved in
      the process. The enhancement of cAMP-induced DNA fragmentation was observed in
      CD4+CD(8+)-double positive cells, but not in CD4+CD(8-)-single positive cells.
      The results of the present study indicate that a physiological cytokine, TNF
      alpha, may modulate programmed cell death in immature thymocytes in concert with
      cAMP.

PMID- 8260601
TI  - Antilipid a monoclonal antibody HA-1A: immune complex clearance of endotoxin
      reduces TNF-alpha, IL-1 beta and IL-6 production.
AB  - HA-1A is a human monoclonal IgM antibody which recognizes the lipid A component
      of lipopolysaccharide (LPS). This antibody has reduced mortality in the septic
      shock syndrome resulting from Gram negative bacteria, in which many of the
      manifestations are considered to be due to cellular activation and secretion of
      cytokines, most notably TNF-alpha. However HA-1A does not directly neutralize LPS
      effectively in vitro, and studies reported to date have not defined its mechanism
      of action. Here we demonstrate that HA-1A, which in the presence of complement
      promotes immune adherence, may inhibit LPS action by facilitating its
      sequestration on red blood cells and clearance to an extent that cytokine
      production is reduced. Incubation of LPS at clinically significant (pg/ml) does
      with HA-1A at therapeutic levels (e.g. 10 micrograms/ml) and complement resulted
      in LPS association with erythrocyte CR1 receptors. This reduced the ability of
      the residual, free LPS by 50-70% to induce the secretion of TNF-alpha, IL-1 beta
      and IL-6 from normal blood mononuclear cells. This mechanism is likely to be
      operative in vivo, and could account for the protective effect of HA-1A, and its
      reduction of TNF-alpha production in vivo.

PMID- 8260602
TI  - Lymphokine production by decidual cells in allogeneic and syngeneic murine
      pregnancy.
AB  - The importance of T cells during pregnancy has been well established in the
      murine system. Depletion of CD4 and/or CD8 positive cells from the maternal
      circulation increases fetal abortion and inhibits placental and fetal growth. T
      cell mediated regulation depends on T cell-derived lymphokines such as IL-6, IL
      10, GM-CSF and IL-3. Among these factors, GM-CSF and IL-3 have been shown not
      only to stimulate trophoblast growth but also to promote placental function. All
      these growth factors having a short half life in vivo must exert their effect
      proximally to the site of production. In the present study, biologically active
      GM-CSF and IL-3 produced by T cells in the maternal decidual cap, which is the
      closet to the fetoplacental unit maternal component, was detected. Cytoplasmic
      staining of total decidual cap cells in various strain combinations, using
      monoclonal antibodies to lymphokines, showed that the numbers of cells producing
      these factors vary depending on the day of pregnancy and on the strain
      combination used. Using indicator cell lines and neutralizing antibodies, it was
      seen that GM-CSF and IL-3 are produced at the eleventh day of pregnancy and
      secreted in both allogeneic and syngeneic pregnancies by decidual cap cells. T
      cell depletion experiments in vivo showed that these factors are produced by T
      lymphocytes. The production and secretion of biologically active CSF-1 was also
      evaluated in this study. Although this is not a T cell-derived lymphokine, it is
      shown to be produced in the uterus and affect trophoblast growth.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260603
TI  - High-affinity and intermediate-affinity forms of the human interleukin 2
      receptor, expressed in an interleukin 9-dependent murine T cell line, deliver
      proliferative signals via differences in their transduction pathways.
AB  - Although several reports have claimed that the p70 IL-2R per se transduces a
      growth signal in lymphoid and non-lymphoid systems, there is no convincing
      evidence for this in lymphoid T cell lines. In order to investigate the mechanism
      of IL-2R-dependent signal transduction pathways via the p70 IL-2R in lymphoid T
      cells, we have established two IL-9-dependent murine (TS1) cell lines stably
      expressing the human p70 IL-2R subunit or the human p55-p70 IL-2R complex.
      Whereas the parental T cell line, TS1, proliferated in response to IL-9 or IL-4
      but not IL-2, cell lines stably expressing human p70 IL-2R or p55-p70 IL-2R
      complex proliferated in response to IL-2. This implies that the murine T cell,
      TS1, contains all the intracellular components necessary for directing IL-2
      signalling. In human p55-p70 IL-2R-transfected cells, the expression of a
      functional murine p55 IL-2R seemed to be induced and regulated by IL-2. In human
      p70 IL-2R-transfected cells, in the presence of IL-2 an interaction requiring
      only intermediate-affinity was sufficient for transduction of a proliferative
      signal. In addition human p70 IL-2R per se, is biologically functional via a
      transduction pathway not requiring induction of murine p55 IL-2R and consecutive
      high-affinity complex reconstitution. Thus, although both transfected cell lines
      can transduce a proliferative signal in the presence of IL-2, a difference in
      their transduction pathway is probably involved for the induction of p55 IL-2R.

PMID- 8260604
TI  - Regulation of Fc-induced IL-6 from human peripheral blood mononuclear cells.
AB  - Previous experiments demonstrated that aggregated immunoglobulin and the Fc
      fragment of human IgG can induce interleukin-6 (IL-6) secretion from peripheral
      blood monocytes. The data herein indicate that Fc-induced IL-6 is modulated by IL
      1, IL-4 and interferon (IFN-gamma). When added with Fc fragments, IL-1 and IFN
      gamma increased IL-6 production. IL-4 added with Fc fragment did not influence IL
      6 production although IL-4 added with LPS was inhibitory to IL-6 production.
      However, when PBMC were pre-treated with IL-4, IL-4 downregulated Fc-induced IL-6
      secretion. The inhibitory effect of IL-4 in the pre-treatment phase could be
      overcome with a high concentration of IFN-gamma added with the IL-4. Both IL-4
      and IFN-gamma acted in a dose- and time-dependent manner. By dot blot analysis,
      IL-6 mRNA production appeared to be decreased in amount and duration by IL-4
      whereas IFN-gamma increased the amount of IL-6 mRNA production. Hence, IL-4 and
      IFN-gamma appear to have opposing effects and may play a balancing role in the
      regulation of IL-6 production secondary to Fc exposure.

PMID- 8260605
TI  - Delineation of positive and negative control elements within the promoter region
      of the murine leukemia inhibitory factor (LIF) gene.
AB  - Leukaemia inhibitory factor (LIF) is a multifunctional growth and differentiation
      factor with activities in both the adult and the embryo. The expression of LIF
      appears to be tightly regulated, as the levels of constitutive expression in most
      tissues and cell lines is extremely low. In this report we have identified three
      sequence elements within the 5'-flanking region of the murine LIF gene which
      control the constitutive action of the LIF promoter. A nested set of DNA
      fragments from the LIF gene 5'-flanking region was placed upstream of the
      chloramphenicol acetyltransferase (CAT) gene and assayed for their ability to
      direct chloramphenicol acetyltransferase (CAT) expression in STO-fibroblasts. The
      essential promoter of the LIF-gene, giving rise to low levels of CAT expression,
      was found to require the major start-site of transcription (+1), a TATA-box (-31)
      and up to 72 additional 5' nucleotides (-32 to -103). A negative regulatory
      element which abolished CAT-activity was identified between positions -360 and 
      249. The SV40 enhancer element was able to override this apparent negative
      element. In addition, an apparent positive control element in the LIF 5'-flanking
      region, between positions -860 and -661 was identified which was also able to
      override this negative effect.

PMID- 8260606
TI  - Inhibition by lactate dehydrogenase-elevating virus of in vivo interleukin 4
      production during immunization with keyhole limpet haemocyanin.
AB  - Interleukin 4 (IL-4) and gamma interferon (IFN-gamma) gene expression in lymph
      node cells from mice immunized with keyhole limpet haemocyanin in the presence of
      complete Freund's adjuvant was analysed by polymerase chain reaction. This
      immunization clearly induced the expression of IL-4 message, whereas IFN-gamma
      message was only slightly increased. A concomitant infection with lactate
      dehydrogenase-elevating virus drastically decreased IL-4 expression whereas IFN
      gamma message was not modified. Analysis of the kinetics of cytokine production
      indicated that the virus did not induce a mere change in the timing of lymphokine
      production, but a persistent inhibition of IL-4.

PMID- 8260607
TI  - Oscillatory brain activity during a motor task.
AB  - Changes in spectral power in neuromagnetic fields associated with a manual task
      requiring a high level of sensorimotor integration (SMI) were investigated by
      analysing spontaneous, non-invasively recorded activity during motor preparation
      (WAIT), task performance (SMI), and control (REST) conditions in four healthy,
      right-handed human subjects. Neuromagnetic fields were recorded over the left
      sensorimotor cortex using a 37-channel instrument. In all subjects, a prominent
      narrow-band motor preparation rhythm centered near 19 Hz was consistently
      observed during the WAIT state. During SMI, mean relative increases in 26-30 Hz
      activity appeared in two of the subjects, paralleling gamma band enhancement
      recently observed during SMI in monkeys.

PMID- 8260608
TI  - Activation of precentral and mesial motor areas during the execution of
      elementary proximal and distal arm movements: a PET study.
AB  - Regional cerebral blood flow was measured using positron emission tomography
      (PET) in normal subjects while performing simple aimless proximal and distal arm
      movements. The aim of the experiment was to compare the somatotopic organization
      of precentral and mesial (the so called supplementary motor area, SMA) motor
      cortices and to evaluate whether in man, as in the monkey, the rostral and caudal
      sectors of SMA are functionally different. The results showed that proximal and
      distal arm movements are to a large extent segregated in the precentral motor
      cortex, but not in the SMA. They also showed that the SMA is made of at least two
      functional sectors. Only the caudal one is activated during simple aimless
      movements.

PMID- 8260609
TI  - GAP43 identifies developing muscle cells in human embryos.
AB  - GAP43 has long been regarded as a neurone specific molecule present
      intraneuronally in both the central and peripheral nervous system, especially
      during development and regeneration. GAP43 has, however, recently been
      demonstrated in developing muscle cells of the chicken. In the prsent
      investigation, we have used immunohistochemistry to investigate whether GAP43 is
      also expressed in developing human muscle cell. Using specific monoclonal
      antibodies as markers for developing muscle cells (desmin) and axon terminals
      (synaptophysin), our results show that GAP43 is expressed in aneural, human
      embryonic muscle cells.

PMID- 8260610
TI  - Transneuronal viral labelling of rat heart left ventricle controlling pathways.
AB  - Retrograde transneuronal viral labelling and immunocytochemical methods were used
      for revealing neuronal networks controlling the left ventricle myocardium of the
      rat heart. After injections of 1 microliter pseudorabies virus solution (3 x
      10(6) PFU ml-1) into the left ventricle, infected orthosympathetic preganglionic
      cells were found in the intermediolateral cell groups of the first 6 thoracic
      spinal segments. Preganglionic parasympathetic neurones were seen both in the
      nucleus ambiguus/retro-ambiguus area and the dorsal motor vagus nucleus. Large
      numbers of infected projecting interneurones were found in the rostral, caudal
      and medial parts of the ventral medulla oblongata, the Kolliker-Fuse nucleus and
      catecholaminergic cell group A5 and in the paraventricular hypothalamic nucleus.

PMID- 8260612
TI  - Colocalization of NGF receptor with VIP in rat suprachiasmatic neurones.
AB  - Low-affinity nerve growth factor receptor (p75NGFR) and vasoactive intestinal
      polypeptide (VIP) immunoreactive neuronal structures and their interrelationship
      were investigated at light and electron microscopic levels in rat suprachiasmatic
      nucleus (SCN). p75NGFR immunoreactive neuronal perikarya were detected in the
      ventrolateral part, while the dorsolateral region contained mainly receptor
      positive fibres. Double-label immunocytochemistry showed that nearly all p75NGFR
      positive neurones in the ventrolateral region of the SCN also contained VIP. The
      axons of the receptor positive neurones terminated on unidentified neurones. In
      single-label experiments, the axons of the VIP containing neurones formed
      axodendritic synapses on cells containing the same peptide. The findings provide
      further insight on the chemical structural organization of the SCN.

PMID- 8260611
TI  - Striatal D2/acetylcholine interactions: PET studies of the vesamicol receptor.
AB  - The regional cerebral distribution of [18F]NEFA, an aminobenzovesamicol (ABV),
      was studied in primates with PET. The binding was stereoselective and could be
      blocked but not displaced with vesamicol. The regional distribution pattern at
      late times, striatum > cortex > cerebellum, was corroborated by in vitro
      autoradiography using [3H]ABV and is consistent with known patterns of
      cholinergic innervation. Pretreatment with sigma 1 or D1 antagonists did not
      affect the striatal uptake, whereas D2 antagonists markedly augmented the uptake.
      This is consistent with the known induction of acetylcholine turnover in the
      striatum in response to D2-receptor blockade and demonstrates that the amount of
      [18F]-(-)-NEFA incorporated was influenced by the cholinergic activity in the
      target neurones.

PMID- 8260613
TI  - Model of topographic map development guided by a transiently expressed repulsion
      molecule.
AB  - The projection from the retina develops into a precise map of the visual world on
      the surface of the tectum. The search for molecular position cues that mediate
      map formation has recently yielded a tectal molecule that exerts a repulsion to
      fibers from the entire temporal half retina. This molecule appears not to
      function in the generally accepted gradient manner but instead provides only
      binary position information, and it is only expressed transiently during early
      development. Here we describe modeling results that compare the efficacy of
      binary versus graded position cues in topographic map formation; the model also
      includes an activity dependent process. We find that binary repulsion is more
      efficient than graded chemoaffinity in the rapid establishment of map polarity,
      and transient expression of either cue provides sufficient guidance for precise
      map formation.

PMID- 8260614
TI  - Muscarinic (M1) mediation of hippocampal spontaneous theta rhythm in freely
      moving cats.
AB  - The effects of intrahippocampally applied different doses of muscarinic (atropine
      sulphate, pirenzepine, gallamine) and nicotinic (hexamethonium, mecamylamine)
      antagonists on the spontaneous theta rhythm in the cat hippocampal formation were
      investigated. The injections of atropine and pirenzepine abolished spontaneous
      theta but administration of gallamine did not affect the EEG pattern. The
      intrahippocampally administered nicotinic blockers, hexamethonium and
      mecamylamine, were completely ineffective in antagonizing theta waves. The data
      suggest that the spontaneous theta rhythm in the cat is mediated by the M1
      receptor subtype.

PMID- 8260615
TI  - Agonist-induced down-regulation of human 5-HT1A and 5-HT2 receptors in Swiss 3T3
      cells.
AB  - We have used single cell clones of Swiss 3T3 cells transfected with genes for the
      human 5-HT1A or 5-HT2 receptor to study down-regulation and desensitization.
      After pre-incubation of the cells with serotonin agonists, a time-dependent
      decrease in [3H]8-hydroxy-2-(di-n-propylamino) tetralin or [3H]ketanserin binding
      was observed. The pertussis toxin sensitive, 5-HT mediated inhibition of
      forskolin-stimulated cAMP accumulation in 5-HT1A receptor transfected cells was
      diminished by 68% after a 2 h pre-incubation of the cells with 10 microM 5-HT.
      The pertussis toxin insensitive, 5-HT mediated PI turnover in 5-HT2 receptor
      transfected cells was decreased by 65% after pre-treatment. While this decrease
      was paralleled by a decreased potency of 5-HT to stimulate PI turnover, in 5-HT1A
      cells the potency of 5-HT to inhibit cAMP formation was comparable to control
      values. The down-regulation and desensitization of the 5-HT2 receptor can be
      explained by phosphorylation via activated PKC. In contrast, the attenuation of
      the 5-HT1A receptor-coupled inhibition of cAMP accumulation has to occur by an
      alternative, as yet unknown, molecular mechanism.

PMID- 8260616
TI  - Localization of [125I]omega-conotoxin GVIA binding in human hippocampus and
      cerebellum.
AB  - The peptide toxin omega-conotoxin GVIA (omega-CgTx) has been shown to be a high
      affinity ligand for N-type calcium channels in the brain. We have employed
      [125I]omega-CgTx to localize N-type channels in human hippocampus and cerebellum
      using autoradiography. Ten micron thick slide-mounted tissue sections of human
      cerebellum and hippocampus were labeled with [125I]omega-CgTx under various
      conditions. Specific binding to human cerebellum was virtually irreversible and
      saturable. It was displaceable by the N-channel antagonist, omega-conotoxin
      MVIIA, but not by L- or P-channel ligands. Binding sites were heterogeneously
      distributed with denser binding in the molecular layer than the granule cell
      layer of cerebellum and with specific laminar patterns evident in the
      hippocampus. [125I]omega-CgTx should be a useful tool for the study of N-type
      calcium channels in human brain tissue.

PMID- 8260617
TI  - Expression and novel subunit isoforms of glutamate receptor genes GluR5 and
      GluR6.
AB  - Molecular heterogeneity of kainate-selective glutamate receptor subunits GluR5
      and GluR6 was revealed by identification of a human cDNA, GluR5-1d, and a murine
      cDNA, GluR6-2, that each encode subunits with novel carboxy-terminal sequences.
      Both GluR5-1d and GluR6-2 appear to be generated by alternative splicing at
      analogous sites 14 codons following the fourth putative transmembrane segment.
      The principal transcripts of GluR5 and GluR6 were detected by Northern analyses
      of several regions of mammalian brains as 4 and 6 kb bands, respectively.
      Potential roles for these receptors in development are indicated by detection of
      their mRNAs in mouse embryos of 11 days gestation. These findings add to the
      description of the remarkable diversity of glutamate receptor gene expression.

PMID- 8260618
TI  - Expression of alpha-actinin in the stereocilia of hair cells of the inner ear:
      immunohistochemical localization.
AB  - The distribution of alpha-actinin was studied on surface preparations and
      cryosections from the organ of Corti of the adult rat by using polyclonal and
      monoclonal antibodies to smooth muscle alpha-actinin. The polyclonal antibody
      used gave a positive immunoreactivity in the cuticular plate of the hair cells,
      pillar cells and supporting cells. A specific labelling of the stereocilia of the
      outer hair cells (OHCs) and inner hair cells (IHCs) on surface preparations was
      highly visible. The monoclonal antibody used produces similar patterns of
      labelling in the organ of Corti. The possible roles of this protein in hair cells
      are discussed.

PMID- 8260619
TI  - Middle ear procaine injection before surgical labyrinthectomy reduces nystagmus.
AB  - A middle ear injection of 2% procaine (0.1 ml) was given to guinea-pigs 15-30 min
      before a surgical unilateral labyrinthectomy (UL) and the effects on spontaneous
      ocular nystagmus (SN) were observed. The pre-UL injection of procaine
      significantly reduced SN frequency compared to vehicle-injected controls or to
      animals receiving a post-UL injection of procaine. This result supports the
      hypothesis that the decrease in resting activity observed in vestibular nucleus
      neurones following UL may be due, at least in part, to Ca2+ influx due to injury
      related glutamate release from vestibular nerve terminals.

PMID- 8260620
TI  - Phonetic invariance in the human auditory cortex.
AB  - Neuromagnetic signals evoked by synthesized syllables (/bae/ and /gae/) were
      recorded over the left auditory cortex of healthy humans. The fundamental
      frequencies of the syllables varied as if the same speaker had pronounced them at
      16 different pitches. Specific mismatch responses to infrequent syllables among
      frequent syllables of the other type indicated that phonetically invariant
      information had been extracted at the level of the auditory cortex from the
      extensive irrelevant pitch variation. Such a detection mechanism is necessary for
      perceiving speech sounds in natural situations with a great deal of acoustic
      variation present.

PMID- 8260621
TI  - Paradoxical selective recovery in a bilingual aphasic following subcortical
      lesions.
AB  - In monolinguals, not only cortical areas but also specific subcortical structures
      are crucial for language and speech processing. While the role of the left basal
      ganglia in monolingual aphasia has been defined, its relevance in bilingual and
      polyglot aphasia is still unknown. Data have now been obtained on a patient who,
      following an ischaemic lesion not involving cortical structures and mainly
      confined to the left basal ganglia, showed severe impairments in mother tongue
      production, with significantly better performance in her hardly spoken second
      language. This dissociation remained stable for over a year and was observed both
      in spontaneous speech and in translation tasks. This pattern of linguistic
      performance, which has never been described in relation to subcortical lesions,
      suggests that the left basal ganglia play a relevant role in the output of a
      highly automatized language.

PMID- 8260622
TI  - Differential, temporal and spatial expression of genes involved in storage oil
      and oleosin accumulation in developing rapeseed embryos: implications for the
      role of oleosins and the mechanisms of oil-body formation.
AB  - The temporal and spatial expression of oleosin and delta 9-stearoyl-ACP
      desaturase genes and their products has been examined in developing embryos of
      rapeseed, Brassica napus L. var. Topas. Expression of oleosin and stearate
      desaturase genes was measured by in situ hybridisation at five different stages
      of development ranging from the torpedo stage to a mature-desiccating embryo. The
      temporal pattern of gene expression varied dramatically between the two classes
      of gene. Stearate desaturase gene expression was relatively high, even at the
      torpedo stage, whereas oleosin gene expression was barely detectable at this
      stage. By the stage of maximum embryo fresh weight, stearate desaturase gene
      expression had declined considerably while oleosin gene expression was at its
      height. In contrast to their differential temporal expression, the in situ
      labelling of both classes of embryo-specific gene showed similar, relatively
      uniform patterns of spatial expression throughout the embryo sections. Immunogold
      labelling of ultra-thin sections from radicle tissue with anti-oleosin antibodies
      showed similar patterns to sections from cotyledon tissue. However, whereas at
      least three oleosin isoforms were detectable on western blots of homogenates from
      cotyledons, only one isoform was found in radicles. This suggests that some of
      the oleosin isoforms may be expressed differentially in the various types of
      embryo tissue. The differential timing of stearate desaturase and oleosin gene
      expression was mirrored by similar differences in the timing of the accumulation
      of their ultimate products, i.e. storage oil and oleosin proteins.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260623
TI  - The pea late nodulin gene PsNOD6 is homologous to the early nodulin genes
      PsENOD3/14 and is expressed after the leghaemoglobin genes.
AB  - The pea late nodulin gene PsNOD6 has been cloned and sequenced. PsNOD6 is
      homologous to the pea early nodulin genes PsNOD3 and PsENOD14. In situ
      hybridization experiments showed that, like the PsENOD3 and PsENOD14 genes, the
      PsNOD6 gene is only expressed in the infected cell type. The PsNOD6 gene is first
      expressed at the transition of the pre-fixation zone II into the interzone II-III
      (the amyloplast-rich zone preceding the fixation zone III), whereas the early
      nodulin genes PsENOD3 and PsENOD14 are already induced in the pre-fixation zone
      II. Thus these nodulin genes encoding homologous proteins are induced at
      consecutive stages of nodule development. The expression of the late nodulin
      genes encoding leghaemoglobin precedes the expression of the late nodulin gene
      PsNOD6. Therefore these late nodulin genes have to be regulated by different
      mechanisms despite the fact they are expressed in the same cell type. This
      conclusion is consistent with the fact that PsNOD6 lacks one of the conserved
      regions occurring in the promoters of all other late nodulin genes studied.

PMID- 8260624
TI  - Higher-plant cofactor-independent phosphoglyceromutase: purification, molecular
      characterization and expression.
AB  - Cofactor-independent phosphoglyceromutase (PGM) was purified to homogeneity from
      developing castor seed endosperm. Immunological characterization using
      monospecific antisera raised against this protein indicates that the enzyme is
      located in the cytosol and that there is no immunologically related polypeptide
      in the leucoplast from this tissue. Isolation and sequence determination of full
      length cDNA clones for castor and tobacco PGM demonstrate that the protein is
      highly conserved in these plants and is closely related to the maize enzyme. A
      comparison of the amino acid sequence of peptides derived from Neurospora crassa
      PGM with the cofactor-independent enzyme from higher plants demonstrated that
      they are related and may have diverged from a common ancestral gene. The
      previously proposed relationship between higher-plant PGM and alkaline
      phosphatases is not supported by sequence analysis of the castor and tobacco
      enzymes. Expression of the single castor cytosolic PGM gene correlates well with
      other cytosolic glycolytic genes in developing and germinating castor seeds, and
      with the appearance of enzyme activity and PGM polypeptides in these tissues.

PMID- 8260625
TI  - Inhibition of the wheat germ DNA polymerase A activity by the antiviral drug HPA
      23.
AB  - Wheat germ DNA polymerase A, a gamma-like enzyme, recognized efficiently natural
      and synthetic RNA templates, resembling a retroviral reverse transcriptase (P.
      Laquel et al., Biochim Biophys Acta 1048 (1990): 139-148). Ammonium-21-tungsto-9
      antimoniate (HPA-23), an antiviral drug, inhibited the DNA polymerase A
      activities, independently of the template primers used, i.e. activated DNA or
      polyriboadenylic acid oligodeoxythymidylate (poly(rA)-oligo(dT)). The inhibition
      observed in the poly(rA)-oligo(dT)-directed DNA polymerase A activity occurred in
      the presence of either Mg2+ or Mn2+ as divalent cation, and also with the 2'
      fluoro analogue of poly(rA) as template. HPA-23 was a non-competitive inhibitor
      with respect to TTP, activated DNA, poly(rA)-oligo(dT), and poly(dAfl)-oligo(dT).
      A preincubation study showed a reversible HPA-23 binding to DNA polymerase A, in
      the presence of poly(rA)-oligo(dT) as the template primer.

PMID- 8260626
TI  - Isolation and characterization of pollen-specific maize genes with sequence
      homology to ragweed allergens and pectate lyases.
AB  - A cDNA clone (Zm58.1) was isolated by differential screening from a cDNA library
      made to mature Zea mays pollen, and shown to be pollen-specific by RNA blot
      analysis. When this partial-length clone was used to probe a genomic library, a
      similar but distinct pollen-specific genomic clone (68% sequence identity) was
      isolated (Zm58.2). The putative proteins coded for by these two clones show
      sequence homology to several flower-expressed gene products from various plant
      species, including known pollen allergens from short ragweed (Ambrosia
      artemisiifolia), and to pectate lyases from the plant pathogenic bacteria Erwinia
      spp. The two genes map to different chromosomes.

PMID- 8260627
TI  - Sequence analysis of two tandemly linked Em genes from wheat.
AB  - DNA sequences are presented for two members of the wheat Em gene family. The
      sequences correspond to the two linked genes at the Xem-1AL locus. Comparisons of
      these sequences with that of another wheat Em gene and two Em cDNA clones reveals
      substantial homology within the protein-coding regions, and the presence in the
      5'-flanking regions of the genomic sequences of motifs characteristic of ABA
      responsive cis-acting elements.

PMID- 8260628
TI  - Arabidopsis thaliana cor15b, an apparent homologue of cor15a, is strongly
      responsive to cold and ABA, but not drought.
AB  - We previously described a cold-regulated (cor) gene from Arabidopsis thaliana,
      cor15a (formerly cor15), that encodes a 15 kDa polypeptide that is targeted to
      chloroplasts (C. Lin and M. Thomashow, Plant Physiol 99 (1992): 519-525). Here we
      describe an apparent homologue of cor15a, cor15b. cor15b is located immediately
      downstream from cor15a (within 1 kb) and has the same relative 5' to 3'
      orientation as cor15a. The predicted coding regions for the two genes are 82%
      identical at the nucleic acid sequence level. Transcripts for cor15b, like those
      of cor15a, increase dramatically in response to low temperature and exogenous
      application of ABA. However, only cor15a transcripts accumulate to high levels in
      response to drought. The cor15a/cor15b gene pair is the third case in which A.
      thaliana cold-regulated genes have been found to exist as tandem gene pairs with
      the members of each pair being differentially regulated.

PMID- 8260629
TI  - Tissue printing and its applications in self-incompatibility studies.
AB  - In this study, the tissue printing technique has been used to rapidly localize in
      female tissues the presence of specific mRNA representing the products (or some
      of the products) of the self-incompatibility S-locus gene(s). The methodology,
      initially developed for Brassica oleracea (sporophytic self-incompatibility) has
      been successfully employed on Solanum chacoense (gametophytic self
      incompatibility). In the Brassica system tissue printing has allowed rapid
      discrimination between S alleles belonging to class 1 (dominant types) vs. class
      2 (recessive types), and thus parallels findings obtained by restriction
      analyses. In the Solanum system the level of the S-RNase messages was analysed by
      scanning laser densitometry, and it was found that the message levels of the
      allele S14 declined faster than those coming from S13 in mature flowers.

PMID- 8260630
TI  - Molecular cloning and nucleotide sequence cDNA encoding nucleoside diphosphate
      kinase of rice (Oryza sativa L.).
AB  - We isolated a rice cDNA encoding nucleoside diphosphate kinase (NDK, EC 2.7.4.6).
      The deduced amino acid sequence of the rice NDK shows highest homology to spinach
      NDK-I. The rice NDK gene exhibits a strong codon bias (73.8% GC) in the third
      position of the codon. DNA blot analysis indicated that at least single NDK gene
      is present in rice genome.

PMID- 8260631
TI  - Plant-nematode interactions.

PMID- 8260632
TI  - Activation of anthocyanin synthesis genes by white light in eggplant hypocotyl
      tissues, and identification of an inducible P-450 cDNA.
AB  - Eggplant seedlings (Solanum melongena) grown under red light irradiation showed a
      normal morphology with green, fully expanded cotyledons. When the seedlings grown
      under red light were irradiated with ultraviolet-containing white light,
      anthocyanin synthesis was induced in the hypocotyl tissues, especially when a UV
      light supplement was added. The accumulation of pigments was closely associated
      with the expression of genes involved in flavonoid synthesis. These genes include
      chalcone synthase (CHS) and dihydroflavonol 4-reductase (DFR). Using subtracted
      probes, which had been enriched for the accumulated mRNA, one white light
      responsive cDNA was identified as being a P450 gene by comparison with database
      sequences. The maximal amino acid homology this cDNA had with other P450s was
      36%. This was with CYP71 from avocado (Persea americana). Thus it represents a
      new P-450 family, which has been named CYP75. The mRNA of this gene was localized
      in the hypocotyl tissues of eggplant seedlings, which had been white light
      irradiated. The transcript was accumulated by changing the light source, as in
      the case of other flavonoid biosynthesis genes. In delphinidin producing petunia
      plants, the mRNAs corresponding to the eggplant P-450 and flavonoid biosynthesis
      genes such as CHS and DFR were most abundant during the mid stage of flower bud
      development, but could not be detected in leaf tissues. These results suggest
      that this P-450 gene encodes a hydroxylating enzyme involved in flavonoid
      biosynthesis.

PMID- 8260633
TI  - Isolation and characterization of a cDNA encoding granule-bound starch synthase
      in cassava (Manihot esculenta Crantz) and its antisense expression in potato.
AB  - A tuber-specific cDNA library of cassava (Manihot esculenta Crantz) was
      constructed and a full-length cDNA for granule-bound starch synthase (GBSS, also
      known as waxy protein), the enzyme responsible for the synthesis of amylose in
      reserve starch, was cloned. Sequencing of the cloned cDNA showed that it has 74%
      identity with potato GBSS and 60-72% identity with GBSS from other plant species.
      The cDNA encodes a 608 amino acid protein of which 78 amino acids form a
      chloroplast/amyloplast transit peptide of 8.37 kDa. The mature protein has a
      predicted molecular mass of 58.61 kDa (530 amino acids). Comparison of the GBSS
      proteins of various plant species and glycogen synthase of bacteria showed
      extensive identity among the mature form of plant GBSS proteins, in which the
      monocots and dicots form two separate branches in the evolutionary tree. From
      analysis of the genomic DNA of allotetraploid cassava, it is shown that GBSS is a
      low-copy-number gene. GBSS transcript is synthesized in a number of different
      organs, but most abundantly in tubers. Potato plants were transformed with the
      cassava GBSS cDNA in antisense orientation fused between the potato GBSS promoter
      and the nopaline synthase terminator. The expression of the endogenous GBSS gene
      in these transgenic potato plants was partially or completely inhibited. Complete
      inhibition of GBSS activity by the cassava antisense gene resulted in absence of
      GBSS protein and amylose giving rise to almost complete amylose-free potato
      starch. This shows that also heterologous genes can be used to achieve antisense
      effects in other plant species.

PMID- 8260634
TI  - Nascent transcript-binding protein of the pea chloroplast transcriptionally
      active chromosome.
AB  - This study describes the nascent RNA-binding protein of the pea chloroplast
      transcriptional complex. The protein has been identified by photoaffinity
      labelling of the transcriptionally active chromosome (TAC) which utilizes the
      endogenous plastid DNA as template. UV irradiation of lysed chloroplast or the
      isolated TAC under conditions optimized for transcription photocross-links
      nascent radiolabelled transcripts (up to 250 nucleotides in length) to a 48 kDa
      protein. The photoaffinity labelling of the transcript-binding protein is
      dependent on UV irradiation, is maximal after about 30 min of irradiation, and is
      completely dependent on transcriptional activity; no cross-linkage has been
      observed with pre-synthesized RNA. Cross-linkage is influenced by salts and
      inhibitors in accordance with their effects on transcription. The photoconjugate
      is composed of protein and RNA moieties, and can be hydrolysed by several
      proteases. However, the cross-linked transcript is protected from nucleases until
      the protein is removed. Manganese enhances photoaffinity labelling of the
      transcript-binding protein, and this is paralleled by an increase in total
      transcriptional activity of TAC. This protein was isolated by 2-dimensional
      polyacrylamide gel electrophoresis and the sequence of 15 amino acid residues at
      the amino terminus was determined. The nascent transcript-binding protein appears
      to be involved in the transcription of all three classes of chloroplast genes. We
      also found a polypeptide of identical molecular weight to get cross-linked to
      nascent transcripts in chloroplasts isolated from other legumes such as Cicer
      arietenum, Vigna radiata and Phaseolus vulgaris, and monocots like Zea mays,
      Oryza sativa and Pennisetum americanum.

PMID- 8260635
TI  - The GAPDH gene system of the red alga Chondrus crispus: promoter structures,
      intron/exon organization, genomic complexity and differential expression of
      genes.
AB  - Our previous phylogenetic analysis based on cDNA sequences of chloroplast and
      cytosolic glyceraldehyde-3-phosphate dehydrogenases (GAPDH; genes GapA and GapC,
      respectively) of the red alga Chondrus crispus suggested that rhodophytes and
      green plants are sister groups with respect to plastids and mitochondria and
      diverged at about the same time or somewhat later than animals and fungi. Here we
      characterize the genomic sequences of genes GapC and GapA of C. crispus with
      respect to promotor structures, intron/exon organization, genomic complexity, G +
      C content, CpG suppression and their transcript levels in gametophytes and
      protoplasts, respectively. To our knowledge this is the first report on nuclear
      protein genes of red algae. The GapC gene is G + C-rich, contains no introns and
      displays a number of classic sequence motifs within its promotor region, such as
      TATA, CAAT, GC boxes and several elements resembling the plant-specific G-box
      palindrome. The GapA gene has a moderate G+C content, a single CAAT box motif in
      its promotor region and a single intron of 115 bp near its 5' end. This intron
      occupies a conserved position corresponding to that of intron 1 in the transit
      peptide region of chloroplast GAPDH genes (GapA and GapB) of higher plants. It
      has consensus sequences similar to those of yeast introns and folds into a
      conspicuous secondary structure of -61.3 kJ. CpG profiles of genes GapC and GapA
      and their flanking sequences show no significant CpG depletion suggesting that
      these genomic sequences are not methylated. Genomic Southern blots hybridized
      with generic and gene specific probes indicate that both genes are encoded by
      single loci composed of multiple polymorphic alleles. Northern hybridizations
      demonstrate that both genes are expressed in gametophytes but not in protoplasts
      where appreciable amounts of transcripts can only be detected for GapC.

PMID- 8260636
TI  - DNA sequence requirement of a TATA element-binding protein from Arabidopsis for
      transcription in vitro.
AB  - We have analyzed the DNA sequence requirements for the functioning of TATA
      elements by examining the transcriptional activities associated with 24
      promoters, including representatives of each of the 21 point mutations in the
      consensus sequence from plants, TATATATA, in a HeLa in vitro system and in a
      chimeric in vitro system in which human TATA-binding protein (hTBP) was replaced
      by purified TBP of Arabidopsis (aTBP-1). Although the relative transcriptional
      activities varied among these promoters, both systems gave virtually identical
      results. Among the mutant TATA elements, those with the sequences TAGAGATA and
      GAGAGAGA had undetectable activity. The rest had activities that ranged from 7%
      to 130% of the activity associated with the consensus element. These results
      suggest the functional conservation of TBP between plants and animals.

PMID- 8260637
TI  - Complaint and disciplinary systems in dentistry in Sweden: a presentation and
      discussion of their efficacy in preventing malpractice.
AB  - The Swedish systems for complaints and supervision with many possibilities of
      claiming on different levels may lead to prevention of future problems in medical
      and dental care. The systems are corrective, preventive and compensatory, and are
      important in the process of quality assurance. However, some elements need
      improvement. The present paper gives as a background an overview of the Swedish
      systems and discusses a few cases. Comparisons with systems in other countries,
      especially the USA, are made, and new measures are discussed. There is a need for
      smooth, preventive measures as well as strong, punitive and corrective measures.
      Recidivist doctors/dentists must be stopped.

PMID- 8260638
TI  - Assessing quality of life in leukemia: presentation of an instrument for
      assessing quality of life in patients with blood malignancies.
AB  - The Life Ingredient Profile (LIP)--a new instrument for iterated quality of life
      assessments in patients with haematological malignancies--is presented. It is
      intended to reflect the patient's estimation of the symptoms of disease as well
      as the side-effects of treatment and is designed for comparing different regimens
      of chemotherapy. In a pilot study of 35 patients with myeloma, lymphoma and acute
      leukaemia, the LIP showed good validity, reliability and sensitivity to change.
      It was easy to apply and the structured interviews took only 10-20 min. LIP
      appears to assess important dimensions of quality of life without being a burden
      to the patient or the nursing staff.

PMID- 8260639
TI  - Evaluation of the appropriateness of plain chest film in chronic diseases.
AB  - OBJECTIVE: To improve continuity of care and appropriateness of plain chest film
      orders in patients suffering from chronic diseases (hypertension, chronic
      obstructive pulmonary disease (COPD) and lung tuberculosis. DESIGN: Retrospective
      evaluation study using explicit and normative consensued criteria. SETTING: Urban
      health center. RESULTS: Compliance with the continuity criteria was 48%, 65% and
      76% in three successive evaluations. Compliance with the appropriateness criteria
      was 52% and 62%. Orders from patients with COPD were responsible for most of the
      lack of compliance. Causes of non-compliance with the continuity criteria were
      attitude and organizational problems; with regard to appropriateness, the main
      cause was external to the Health Center. CONCLUSIONS: (1) Difficulty in improving
      registers, reflecting a defect in the continuity of care. (2) Usefulness of
      evaluation in discovering the causes of the problems, in these cases an external
      one. (3) Difficulty of improvement when the cause of the problem is external to
      our own setting. (4) Partial effectiveness of continuing education measures
      because of professional changes in the Health Center.

PMID- 8260640
TI  - Radiation oncology: quality assurance and cost-effectiveness in Australia.
AB  - The purpose of this study was to develop a data set consisting of measures of
      treatment outcome and cost, capable of standardization across radiation oncology
      facilities in Australia. Using a detailed consultative process involving
      representatives of a wide variety of professional organizations including the
      Royal Australasian College of Radiologists, the study identified the items
      necessary for inclusion in a data collection instrument to allow assessment of
      treatment modalities, quality of care, comparative efficiency and cost
      effectiveness of radiation oncology services. The instrument has been tested by a
      pilot study and the results indicate that the items included in the instrument
      have received acceptance amongst health care providers.

PMID- 8260641
TI  - Preceptorship in clinical nursing education in Sweden: aspects of quality
      assurance.
AB  - Nursing education in Sweden is in a changing phase and the aim of this study is
      to describe a group of nurse preceptors and explore some of the factors that are
      believed to be of importance to clinical teaching according to the current model.
      Staff nurses (N = 86) who served as preceptors to students during their main
      clinical training in the areas of surgical, medical and long-term care
      participated in the study. Data were collected by means of a questionnaire
      designed for the study and the Nurse Self Description Form (NSDF). The results
      revealed that 39% of the preceptors had less than two years experience as
      Registered Nurses and 30% were less than 26 years old. These less experienced
      preceptors evaluated the amount of education they had received concerning the
      nursing process and related subjects as significantly higher when compared to the
      more experienced nurses. Approximately one fourth of the preceptors (N = 23) were
      using care planning in their ordinary work and another 29 had prior experience,
      but many preceptors (N = 34, 39%) had no direct experience of individualized care
      planning. Although there was a great deal of variance, the preceptors' estimation
      of their own professionalism such as in teaching, leadership and knowledge
      mastery as measured by the NSDF did not reveal any significant differences from
      ordinary nurses in a reference group. It is concluded that the quality of the
      important clinical part of nurse education may vary according to individual
      experience and knowledge of the preceptors.

PMID- 8260642
TI  - Quality of rehabilitation care in two inpatient geriatric settings.
AB  - The study assessed the quality of care in 410 geriatric patients admitted for
      rehabilitation following a hip fracture (53%) or stroke (47%) to two types of
      inpatient setting: geriatric departments in general hospitals (GDs) and free
      standing geriatric hospitals (GHs), 45% and 55% of patients, respectively. The
      assessment of care was based on two outcome criteria, change in functional status
      (Barthel Index) and patient destination on discharge. Findings suggest that
      rehabilitation performed in GHs had some advantage over that in GDs although the
      cost of stay in GHs is half of that in GDs, and GHs seem to be also more cost
      efficient. The finding indicates one way in which assessment of quality
      contributes to health policy and planning.

PMID- 8260643
TI  - Perceived needs and patient satisfaction in relation to care provided in
      individuals with rheumatoid arthritis.
AB  - A cross-sectional study was performed upon a group of patients (N = 222) with
      rheumatoid arthritis (RA), from a Swedish health care district. The aim was to
      elucidate expectations and satisfaction with health care workers. The
      participants indicated that a good reception is more important than professional
      knowledge followed by the ability to inform about RA and the ability to show
      empathy. There was a trend towards increasing satisfaction with information about
      medical problems with severity of RA. This stands in contrast to the lack of such
      a systematic relation with regard to increasing functional disability as measured
      by the Stanford Health Assessment Questionnaire. Reasons for this could be that
      the physicians tend to respond more to clinical signs than to daily living
      restrictions. A relatively high percentage (around 80%) of the patients were
      satisfied with the surgical procedures offered to them. Only one third of the
      individuals felt that they had been involved in planning of treatment and
      discharge although a majority expressed this as very important. The importance of
      a continuous dialogue between patient and physician with regard to fulfillment of
      patient expectations is emphasized.

PMID- 8260644
TI  - Quality requirements in nursing departments: development and use of a general
      framework.
AB  - The nursing staff of the Nijmegen University Hospital has implemented a project
      to formulate and evaluate objectives of quality of care. A quality profile,
      formulated on a national level, has been used as a guide in quality projects at
      nursing units for four years. The results of these quality projects show a lot of
      definite quality improvements and also a large number of quality requirements. In
      1991 an inventory was made of these requirements. A specific method was used to
      select these requirements. Finally, a new framework of quality requirements was
      formulated. This framework offers the Nijmegen University Hospital possibilities
      such as: (i) being a source from which targets may be selected for quality
      improvement projects; (ii) requirements being made operational and used to
      measure the quality of nursing care.

PMID- 8260645
TI  - Design and results of the nursing quality assurance program in Hospital de la
      Santa Creu i Sant Pau: an integrated effort.
AB  - This paper aims to describe and evaluate the results of the Nursing Quality
      Assurance (QA) Program in the Hospital de la Santa Creu i Sant Pau. The program
      was designed in 1987 as part of a global QA program involving all aspects of
      patients' care. The QA Program was organized at three levels: hospital, ward and
      joint medical-nursing. During the first 3 years of the study the following
      activities were carried out: (A) nursing process and results; (B) risk
      management; (C) patients' opinion; (D) utilization review; (E) ward nursing QA
      programs. Among other significant results, the program has detected that only
      55.6% patients manifest that they sleep well at hospital, hygiene of dependent
      males (51%) is significantly worse than dependent females (81%) and patients'
      falls are more prevalent among oriented patients (73%) than disoriented patients
      (27%). Also a significative improvement has been demonstrated after implementing
      corrective measures in patients' information (7.5/10-8.1/10) and patients without
      supervision in emergency areas became from 35% to 0.02%. New nursing records were
      designed as a result of the QA assessment. The most important conclusion is that
      the Nursing QA Program is a valid instrument to evaluate general problems in the
      hospital and concrete problems in each ward.

PMID- 8260646
TI  - The interleukin-2 receptor complex and signal transduction: role of the beta
      chain.
AB  - Proliferation of lymphocytes is regulated by a variety of cytokines, among which
      interleukin-2 (IL-2) is well characterized for its potent ability to promote cell
      growth. The IL-2 signal(s) is transmitted to the cell interior via its homologous
      receptor (IL-2R). The functional high affinity IL-2R is a multichain complex
      consisting of at least three distinct components, IL-2R alpha, beta and gamma.
      None of these components possess an intrinsic protein tyrosine kinase (PTK)
      domain. cDNA expression studies, have revealed the critical role of IL-2R beta,
      but not IL-2R alpha, in the IL-2R-mediated intracellular signaling process.
      Studies utilizing mutants of IL-2R beta identified an essential cytoplasmic
      region, defined as the 'serine-rich' region, for IL-2-induced cell growth. With
      respect to the involvement of PTK(s) in IL-2R mediated signal transduction, it
      has been demonstrated that p56lck, a member of the src-family PTKs interacts with
      the IL-2R beta. In fact, IL-2 stimulation increases the PTK activity of p56lck.
      Another cytoplasmic region of the receptor, defined as the 'acidic' region has
      been found to be critical for the association of p56lck with the IL-2R beta.
      Interestingly the 'serine-rich' and 'acidic' regions of IL-2R beta are both
      required for the PTK activation of p56lck. Expression studies with mutant IL-2R
      beta cDNAs have revealed a bifurcation in the IL-2 signaling pathway. One pathway
      involves the src-family PTK activation which is linked to the activation of
      p21ras and the subsequent induction of c-fos/c-jun protooncogenes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260647
TI  - Interleukin-2 receptor heterotrimer complex and intracellular signaling.
AB  - Identification of a third component of the IL-2 receptor complex, gamma-chain,
      has established that the high-affinity complex consists of at least three
      distinct subunits, alpha-, beta- and gamma-chains. The alpha-chain specifies the
      low-affinity IL-2 binding. The beta- or gamma-chains alone do not show any
      appreciable IL-2 binding activity, however simultaneous existence of both chains
      generates a functional receptor complex that is suggested to associate with a non
      receptor type protein tyrosine kinase that may deliver IL-2-induced signals
      further downstream. Mutation studies have revealed that discrete cytoplasmic
      regions of the beta- and gamma-chains transduce at least two independent
      signaling pathways.

PMID- 8260648
TI  - Regulation of PtdIns-3-kinase and the guanine nucleotide binding proteins p21ras
      during signal transduction by the T cell antigen receptor and the interleukin-2
      receptor.
AB  - The T cell antigen receptor (TCR) and the interleukin-2 receptor (IL-2R) are
      important receptors in haematopoiesis since they control the activation and
      growth of T lymphocytes, respectively. The term T cell activation refers to the
      events that occur as T cells progress from the G0 to the G1 phase of the cell
      cycle and is characterised by the production of a wide range of cytokines and
      other immunomodulators crucial for the growth and development of other
      haematopoietic cells. Activation also induces the T cells to express on their
      cell surface high affinity receptors for various cytokines which enable the T
      cell to respond to the different cytokines generated during an immune response.
      One well characterised event that occurs when mature T cells are activated is the
      production of the cytokine IL-2 and the acquisition by the T cell of high
      affinity IL-2 receptors. Interaction between IL-2 and its cellular receptor than
      direct T cell growth. One notable difference between TCR and IL-2R signal
      transduction is that the TCR regulates intracellular calcium and stimulates
      protein kinase C whereas the IL-2 receptor does not. The present review focuses
      on TCR and IL-2R regulation of two common intracellular signalling pathways: the
      regulation of a PtdIns-3-kinase and the activation of the guanine nucleotide
      binding proteins p21ras. The aim is to illustrate differences in the mechanisms
      that couple the TCR and IL-2R to these two signalling pathways and attempt to
      explain the apparent discrepancy of TCR and IL-2R regulation of shared signal
      transduction pathways even though these receptors mediate quite distinct
      biological responses.

PMID- 8260649
TI  - Protooncogene-encoded protein kinases in interleukin-2 signal transduction.
AB  - Protooncogenes are the normal forms of cellular genes that when altered in their
      expression or coding sequences can contribute to neoplastic transformation. As
      these genes often are important for normal cellular growth control, we explored
      the possibility that protein kinases encoded by particular protooncogenes could
      participate in signal transduction pathways regulated by the T cell growth
      factor, interleukin-2 (IL-2). In this review we summarize our findings to date
      regarding Raf-1, a serine/threonine-specific kinase that becomes phosphorylated
      on tyrosine residues and enzymatically activated in response to IL-2 stimulation.
      In addition, we describe our investigations of Lck and Lyn, two closely related
      protein tyrosine kinases of the src gene family that physically associate with
      the IL-2 receptor complex and whose activities are regulated by IL-2 in at least
      some T cells and B cells, respectively.

PMID- 8260650
TI  - Protein and lipid kinase activation cascades in interleukin-2 receptor
      signalling.
AB  - The signalling mechanisms of the IL-2R remained an enigma until recent years. We
      now know that IL-2R are coupled to their own unique signalling pathways that
      complement rather than duplicate TCR signalling. The IL-2R beta- and gamma-chains
      are essential for signal coupling. Sequence comparisons indicate that portions of
      the extracellular and cytoplasmic domains of IL2R beta gamma molecules are
      homologous to several hematopoietic growth factor receptors, including
      erythropoietin. This may indicate that these receptors utilize common or related
      molecules in ligand binding or signal transduction. The cytoplasmic domain of the
      IL-2R beta-chain contains distinctive serine (S) and acidic (A) rich regions that
      participate in signalling. The overall scheme of IL-2R signalling is similar to
      other eukaryotic growth factors in that ligand binding activates a complicated
      and branching series of enzymatic steps that utilize protein tyrosine kinase
      (PTK) activation as a central component. More recent reports indicate that IL-2R
      are linked to additional membrane and cytosolic signalling molecules, including
      glycosylated phosphatidylinositol (GPI), phosphatidylinositol-3-kinase (PI3K),
      p74c-raf and p21ras. The regulation of these factors and their importance in IL-2
      induced growth and differentiation awaits further study.

PMID- 8260651
TI  - Transmembrane signaling by the interleukin-2 receptor: progress and conundrums.
AB  - Activation of the multicomponent interleukin-2 receptor (IL-2R) complex leads to
      a rapid increase in tyrosine phosphorylation of a number of cellular proteins
      including the IL-2R beta and IL-2R gamma chains of the IL-2R and the RAF-1 serine
      threonine kinase. In addition, phosphatidylinositol 3-kinase (PI-3K) protein and
      activity can be immunoprecipitated with anti-phosphotyrosine and anti-IL-2R beta
      antibodies from IL-2-activated but not resting T lymphocytes. We have
      demonstrated that the SH2 (SRC homology 2) domains of the 85 kDa subunit of PI-3K
      are sufficient to mediate binding of the PI-3K complex to tyrosine
      phosphorylated, but not non-phosphorylated IL-2R beta, suggesting that tyrosine
      phosphorylation is an integral component of the activation of PI-3K by the IL-2R.
      Since none of the members of the IL-2R complex contains an intrinsic tyrosine
      kinase domain, IL-2-induced tyrosine phosphorylation must be the consequence of
      activation of intracellular tyrosine kinases. SRC family members including lck,
      lyn and fyn have been demonstrated to associate with IL-2R beta through binding
      of the kinase domain to the acidic domain of IL-2R beta. However, we have
      demonstrated that the serine rich (SD) region of the cytosolic domain of IL-2R
      beta is also required for association of a tyrosine kinase with the IL-2R complex
      and that IL-2 can induce proliferation and tyrosine phosphorylation in cell lines
      which lack the known SRC family kinases expressed by T lymphocytes. Thus members
      of other kinase families besides SRC may also be involved in mediating IL-2
      signal transduction. Biochemical studies and studies of cells expressing mutant
      IL-2 receptors indicate that IL-2-induced tyrosine kinase activation initiates a
      complex signaling cascade. The cascade includes SRC family kinase members such as
      lck, fyn, and lyn, activation of Raf-1 and PI-3K, and ras, and increased
      expression of the fos, fra-1, and jun protooncogenes. In addition, ligation of
      the IL-2R leads to rapid increases in myc expression and more delayed increases
      in the expression of the cdc2 and cdk2 kinases and the cyclins through a tyrosine
      phosphorylation independent pathway. Whether other biochemical processes
      initiated by IL-2R ligation, including activation of the MAP2, p70S6 and p90RSK
      serine threonine kinases, activation of NF-kappa B, and increased expression of
      Raf-1, Pim-1, bcl-2, IL-2R alpha and IL-2R beta, are consequences of the IL-2
      induced tyrosine kinase cascade remains to be determined.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8260652
TI  - Tactics for the isolation of interleukin-2-induced immediate-early genes.
AB  - Interleukin-2 (IL-2), a 15 kDa protein secreted by antigen-activated T
      lymphocytes, plays a central role in the generation of an immune response.
      Initially characterized as a T cell growth factor, IL-2 has subsequently been
      found to act on all lymphoid cell types, inducing both their proliferation and
      functional differentiation. The effects of IL-2 are mediated by the activation of
      a specific cell-surface receptor (IL-2R), which is comprised of at least three
      distinct proteins. Early biochemical signaling events triggered upon IL-2R
      activation have recently begun to be elucidated, and a number of genes have been
      identified which are specifically induced by IL-2. The task now at hand is to
      link the biochemical signaling pathways activated by IL-2 with the regulation of
      gene expression, and to delineate the roles of these gene products in IL-2
      mediated proliferation and differentiation.

PMID- 8260653
TI  - Signal transduction through the receptor for erythropoietin.
AB  - Erythropoietin (EPO) supports the proliferation and differentiation of erythroid
      lineage cells. The receptor for erythropoietin is a member of the cytokine
      receptor family. Introduction of EPOR into IL-3 dependent cells confers the
      ability to proliferate in response to EPO. Associated with this, EPO induces the
      expression of a number of immediate-early response genes. Mutagenesis studies
      have addressed the function role of various motifs and domains in receptor
      function and established essential roles for the conserved cysteines and the
      WSXWS motif. The signal transducing pathways activated by EPOR include induction
      of tyrosine phosphorylation. Within the cytoplasmic domain a relatively small
      membrane proximal region is essential for induction of tyrosine phosphorylation,
      expression of immediate early genes and for mitogenesis. The role of various
      kinases in this response is discussed as well as an assessment of potential
      substrates of tyrosine phosphorylation.

PMID- 8260654
TI  - Microbial infections and occlusal overload: causes of failure in osseointegrated
      implants.
AB  - Microbial infections and occlusal overload are the two primary causes of failure
      in osseointegrated implants. This paper reviews the roles of pathogenic bacteria
      and occlusal overload, summarizes the types of microbes, outlines the diagnosis,
      and discusses how these conditions may be avoided and/or corrected. The learning
      objective of this article is an enhanced and updated understanding of the
      etiology, prevention, and correction of these two conditions.

PMID- 8260655
TI  - The trouble with implants.

PMID- 8260656
TI  - Surgical management of the palato-radicular groove and associated periodontal
      lesion: a case presentation.
AB  - The palato-radicular groove is an anatomic variant which may be associated with
      significant attachment loss. This article illustrates the need to carefully
      examine all patients for the presence of such an anomaly and suggests one
      possible treatment modality in the event an associated periodontal lesion is
      present. The learning objective of this article is the ability to recognize this
      anatomic anomaly and to implement corrective measures.

PMID- 8260657
TI  - A computerized tomography (CT) scan appliance for optimal presurgical and
      preprosthetic planning of the implant patient.
AB  - This article describes the technique for using the CT (computerized axial
      tomography) scans, with specially designed software and an adjunct appliance, for
      accurate planning of dental implants and implant-supported restorations. The
      available bone can be evaluated, surgical problems anticipated, and errors in
      placement avoided. The learning objective of this article is an enhanced
      knowledge of the extended application of the CT scans and the use of the
      orientation and immobilization appliance.

PMID- 8260658
TI  - Walk, don't run.

PMID- 8260659
TI  - A conservative alternate to single tooth replacement: a three-year follow-up.
AB  - This article discusses a clinical procedure/technique for placing a conservative
      bridge in posterior teeth, using a heat-and-pressure-cured resin, reinforced with
      plasma-coated fibers. Several cases are used to illustrate the procedure. The
      learning objective of this article is the understanding of the technique and the
      materials used, thereby enabling implementation.

PMID- 8260660
TI  - Bond strength of a veneering porcelain using newer generation adhesive systems.
AB  - A laboratory study was conducted to determine the shear bond strength of etched
      and silane-treated porcelain to enamel and dentin, using resin cements and newer
      generation adhesive systems. The results of this in vitro study showed excellent
      bond strength of porcelain to acid-conditioned enamel using a new adhesive system
      and a resin cement. The study also found strong bonds between etched and silane
      treated porcelain and dentin, using several newer generation adhesive systems in
      conjunction with resin cements. The learning objective of this article is an
      increased knowledge of the newer generation adhesives with data for material
      comparison.

PMID- 8260661
TI  - Measuring tuberculosis: the role of the Tuberculosis Prevalence Survey as
      developed in Eastern countries.

PMID- 8260662
TI  - Lung diseases in the tropics. Part 1: Tropical granulomatous disorders of the
      lung: diagnosis and management.
AB  - International travel, student and cultural exchanges and changing immigration
      patterns are insidiously transforming the face of medicine in the United States,
      Europe and other developed countries. It is essential that the practising
      clinician be aware of the increasing prevalence of various new and exotic
      tropical lung diseases. The definitive diagnosis of the pulmonary granulomas that
      constitute the bulk of lung disorders in the tropics is important since the
      treatment varies significantly. At the same time, recent developments in
      molecular biology, immunology and biochemistry have increased the diagnostic
      accuracy and therapeutic effectiveness related to tropical granulomatous
      disorders. Clinicians in the developing countries can now supplement their
      clinical acumen with rapid advances in immunology and histopathology enabling
      them to grasp the fundamental mechanisms of granuloma formation. Mycobacterial,
      fungal, parasitic, spirochetal and other infections must be differentiated from a
      variety of non-infectious granulomas including sarcoidosis, hypersensitivity
      pneumonitis, drug reaction and generalized vasculitis since therapy is vastly
      different. The treatment, if inappropriate, may not only be worthless but, in
      many cases, extremely harmful and even fatal.

PMID- 8260663
TI  - Superoxide dismutase activity of Mycobacterium avium complex (MAC) strains
      isolated from AIDS patients.
AB  - OBJECTIVE: To explore whether Mycobacterium avium complex (MAC) strains isolated
      from AIDS patients produce and secrete superoxide dismutase (SOD). DESIGN: SOD
      was assayed in the crude extracts and in cell-free medium of 18 MAC strains (MAC
      101, LR and SK strains) isolated from AIDS patients to determine intracellular
      and extracellular activity. The SODs were characterized by PAGE and by their
      sensitivity to azide, cyanide and hydrogen peroxide. RESULTS: SOD activity was
      detected in cell extracts as well as in extracellular medium of all AIDS-MAC
      strains. PAGE demonstrated a single activity band for each strain, though there
      were differences in mobility. All LR strains demonstrated an activity band with
      Rf = 0.30, while SOD band for MAC 101 and for SK strains migrated further (Rf =
      0.87). The differences in mobility correlated with differences in sensitivity to
      NaN3 and H2O2. The SOD activity of LR strains was irreversibly inhibited 100% by
      5 mM H2O2, and exhibited greater sensitivity to NaN3, suggesting the presence of
      iron in the enzyme. The SOD activity of SK strains and MAC 101, however, was not
      inhibited by 5 mM H2O2 but was inhibited to a lesser extent by NaN3, which is
      characteristic of a manganese-containing SOD. CONCLUSION: Our data indicate that
      MAC strains are rich in manganese- or iron-containing SOD, which could contribute
      to the organism's resistance to the oxidative burst of activated macrophages. The
      secretion of SOD may play an important role in the pathogenesis of MAC strains.

PMID- 8260664
TI  - Turning intermittent regimens into daily regimens using blister-packs. An
      exploration in murine tuberculosis.
AB  - SETTING: Blisterpacks might be used to present low cost intermittent regimens
      while maintaining an easily remembered daily frequency of opening blisters, by
      alternating blisters containing 2 of the drugs of a 4-drug regimen with blisters
      containing the remaining 2 drugs. OBJECTIVE: The efficacy of the alternating
      regimens was examined in murine tuberculosis. DESIGN: 2 weeks after infection
      with Mycobacterium tuberculosis H37Rv, groups of mice were treated with
      rifampicin (R) 15 mg/kg, isoniazid (H) 25 mg/kg, pyrazinamide (Z) 300 mg/kg,
      ethambutol (E) 100 mg/kg three times weekly (RHZE3); RH/ZE, an alternating
      regimen of RH on days 1, 3 and 5 of the week and ZE on days 2, 4 and 6, RZ/HE or
      RE/HZ. RESULTS: Spleen and lung bacillary counts at 7 and 12 weeks indicated
      large differences in the efficacy of the regimens: RZ/HE > RE/HZ > RHZE3 > RH/ZE.
      Serum assays showed that Rifampicin (RMP) levels were much lower after HRZE and
      slightly lower after RZ, RE and RH than after R alone, whereas levels were
      similar when R was given before the remaining drugs; also, the absorption of Z
      was slightly increased by R. A second experiment used the same 4 regimens but
      gave R before other drugs. The organ colony forming units counts at 6 and 12
      weeks were then similar. A third experiment examined continuation phase regimens
      of R3, R2, R2H2 and R2H6 given after daily RHZ treatment for 4 weeks. It found
      R2H2 only slightly superior to R2H6 and R3 much better than R2. CONCLUSION: 1.
      Alternating initial phase regimens were as effective as conventional intermittent
      regimens. 2. R3H6 might be an optimal continuation phase regimen for
      blisterpacks.

PMID- 8260665
TI  - Diagnosis of tuberculous meningitis by detection of immunoglobulin G antibodies
      to purified protein derivative and lipoarabinomannan antigen in cerebrospinal
      fluid.
AB  - Enzyme-linked immunosorbent assay of immunoglobulin G (IgG) activity in
      cerebrospinal fluid (CSF) and sera was conducted prospectively in 27 patients
      with tuberculous meningitis (TBM) by using purified protein derivative (PPD) and
      lipoarabinomannan (LAM) antigens, from January 1989 to August 1990. 29 patients
      with aseptic meningitis and 49 patients with non-inflammatory neurological
      illnesses served as controls. All patients had a computed tomography (CT) scan of
      the head before a lumbar puncture. The IgG antibodies to the antigens were
      significantly elevated in TBM, and the reactivity was more frequently positive in
      the CSF than in the sera, suggesting a local synthesis of IgG in the central
      nervous system (CNS). The sensitivity and the specificity for the diagnosis of
      TBM were 59.2% and 93.9% for PPD antigen, and 85.2% and 95.9% for LAM antigen,
      respectively. Assay of IgG reactivity to LAM antigen was clinically very useful
      for the early diagnosis of TBM and was superior to PPD for detecting the
      serological evidence of TBM.

PMID- 8260666
TI  - Private doctors and tuberculosis control in India.
AB  - Over three quarters of the 8 million registered doctors in India are engaged in
      private medical practice. In urban and rural areas alike people prefer private
      doctors to public health services for their health care needs. A majority of
      patients and those with suspected tuberculosis also report first to private
      doctors. Nevertheless private doctors seem to be alienated from national efforts
      towards control of tuberculosis, there being no well-defined role for them in the
      National Tuberculosis Programme. This study of private doctors practising in the
      low income areas of a metropolis of India reports on the knowledge of private
      doctors about diagnosis and treatment of tuberculosis and their awareness and
      perceptions about the public health services available for tuberculosis control.
      The study reveals gaps and weaknesses in the private doctors' reported practice
      of managing lung tuberculosis, the most important and persistent problem of
      public health concern in India. The need for organized efforts towards involving
      private doctors in disease control programmes wherein their curative functions
      could contribute significantly is stressed.

PMID- 8260667
TI  - Comparative study of a biphasic culture system (Roche MB Check system) with a
      conventional egg medium for recovery of mycobacteria. Aichi Mycobacteriosis
      Research Group.
AB  - OBJECTIVE: The clinical utility of a new biphasic culture system (Roche MB Check
      system) for the recovery of mycobacteria was evaluated in comparison with a
      conventional egg based medium. DESIGN: A total of 905 clinical specimens (mainly
      sputum samples) were tested in 9 clinical microbiology laboratories in Aichi
      Prefecture, Japan. The recovery rate and detection time of mycobacteria from the
      specimens were compared between the biphasic system and the egg medium. RESULTS
      AND CONCLUSION: Of the 905 samples, 311 were positive in the culture of
      mycobacteria. The recovery rate of the biphasic system was superior to that of
      the egg medium (99.0% versus 74.0%, P < 0.0001). In addition, the biphasic system
      showed a considerable decrease in the number of days required for isolation
      compared with the egg medium (18.8 days vs. 23.1 days for Mycobacterium
      tuberculosis, P < 0.0001; 13.4 days vs. 19.8 days for M. avium complex, P =
      0.007). The biphasic system is therefore proposed as a feasible and practical
      method for the recovery of mycobacteria from clinical specimens.

PMID- 8260668
TI  - Polymerase chain reaction for the differentiation of Mycobacterium intracellulare
      and Mycobacterium avium.
AB  - Polymerase chain reaction (PCR) amplification was performed using DNA purified
      from 15 mycobacterial type strains and from 21 specimens isolated from patients
      suspected to have non-tuberculous mycobacterial diseases. Using a primer set of
      MTB1-MTB2, 11 specimens out of 21 were Mycobacterium avium and 8 were M.
      intracellulare, which were verified by the Gen Probe Rapid Diagnostic System for
      the M. avium complex (MAC). One of the remaining 2 specimens which did not
      hybridize with the probe for the MAC was identified as M. kansasii and the other
      was not specifically identified by the conventional culture method. PCR
      amplification, using a primer set of TB1-TB3, was also performed for the specific
      identification of M. tuberculosis complex.

PMID- 8260669
TI  - The supply of antituberculosis drugs and national drugs policies.

PMID- 8260670
TI  - Treatment of tuberculosis in HIV infection.

PMID- 8260671
TI  - The third biovariant of Mycobacterium fortuitum.

PMID- 8260672
TI  - Tuberculosis is increasing in England and Wales.

PMID- 8260673
TI  - [Methodical nursing care with a written nursing care plan as basis].
AB  - A written nursing care plan enables quality nursing care. It is essential for
      primary nursing. As nurses we are on different levels of expert knowledge and we
      have different ways of being committed to our work. If a nurse doesn't recognize
      her basic task it is not possible to recognize it meaningful to provide a written
      nursing care plan. The development of written nursing care plan needs
      professional discussion and evaluation. The skill for written nursing care plan
      needs practising, self-evaluation and feedback. The study of written nursing care
      plans used earlier on the ward reveals professional development. The documented
      needs and problems are now more individual. The problems are solved using means
      of nursing more creatively. Some nursing care plans reveals the need for training
      to obtain more knowledge.

PMID- 8260674
TI  - [Viewpoint on the need for nursing records and timing of record documentation].

PMID- 8260675
TI  - [Emergency nursing and the multiple trauma patient].
AB  - The most important characteristics of nursing care of the acutely ill patients in
      the accident and emergency ward are safety and continuity. To work under pressure
      in periods and to handle many tasks at the same time also are important features.
      This kind of nursing care is very intensive. A patient's vital functions are of
      the first priority. There is no room for own feelings. Those can be analyzed
      afterwards. When the condition of a patient is stabilized there is time for
      holistic nursing and to look for his/her capability to self-care. The nurses of
      Toolo Hospital (University Central Hospital of Helsinki) describe the nursing
      care of the multiple trauma patient. The work is rewarding, one can see the
      results immediately.

PMID- 8260676
TI  - [Hospital ward S7--challenge in self care training. Interview by Kaija Sailo].
AB  - In this article the ward sister of the cardiac patients' ward is interviewed.
      Rehabilitation is interdisciplinary work and it is the natural part of nursing
      care of the cardiac patients from the beginning of care. Rehabilitation organized
      in hospital is supported by weekend courses. These courses have a goal to support
      the patient and his/her family to govern the changed situation in everyday life.
      The patients who have participated in the course declare it lessens the
      adaptation difficulties. It has been possible to develop rehabilitation
      holistically by evaluating these courses.

PMID- 8260677
TI  - [Training for empowerment to increase patients' wellbeing].

PMID- 8260678
TI  - [Educating for quality of life].
AB  - This article describes nursing care of disable in Paimio Hospital. The goal of
      nursing is the optimal life of the disabled considering his/her age and health.
      Primary nursing and community education are the basic principles. Routines and
      function centredness do not exist. Rehabilitation is not separated. Instead it
      means everyday ability and activity. To learn communication skills is a main goal
      for rehabilitation. Another goal is to participate in the activities outside the
      institute and to increase contacts with the environment.

PMID- 8260679
TI  - [Nutritional status and nutrition education].
AB  - Nutrition education is concerned with disseminating nutrition knowledge relevant
      to food behavior. It aims to changes in parallel to nutrition recommendations
      which are seen important in a population level. But in the individual level the
      relationship between knowledge and behavior becomes more complex. Individuals are
      often loaded with controversial nutrition knowledge sometimes too concentrated in
      separate facts and forgetting the whole. The role of the professionals in the
      area of health care is very important as mediators. They should explain to their
      patients or clients how the important changes are put into practice and what kind
      of information is relevant in keeping the whole diet in mind.

PMID- 8260680
TI  - [The role of dietary fats in health].
AB  - The current knowledge shows that the quality and quantity of dietary fat have a
      meaningful role in the etiology and pathogenesis of atherosclerosis. The risk of
      coronary heart disease is positively related to the cholesterol level in the low
      density lipoprotein (LDL) fraction. Cholesterol-lowering diet is recommended for
      everyone. The recommended diet is low in total fat, saturated fatty acids,
      dietary cholesterol and salt and high in fiber.

PMID- 8260681
TI  - [Middle-Finland public health nurses participate in a large-sized longitudinal
      studies. Language development and its relation to reading ability].
AB  - Dyslexia, specific reading disability, which seriously impairs school achievement
      and interferes with the acquisition of information, is estimated to affect about
      3-15% of the population. In a longitudinal study started in the University of
      Jyvaskyla researchers will follow the development of language and other cognitive
      skills of babies of 160 families from birth to about 10 years' age in search for
      early precursors of dyslexia. Trough screening parents for dyslexia we hope to
      obtain new information about specific features of reading and writing problems in
      adulthood, which helps us to focus our search for important features of early
      language problems linked to development of dyslexia. Finnish public health nurses
      are involved the study in the field.

PMID- 8260682
TI  - [True presence and interaction? Patients' and nurses' "common existence"].
AB  - This article explores the questions of interrelationship and the way of existence
      of a nurse and patient. The intent is to engage readers in deep reflection of
      one's own nursing and the core of nursing. This is the way to see the essence of
      nursing e.g. to help a patient in experiencing good quality care and to see it's
      meaning for his/her wellbeing.

PMID- 8260683
TI  - [Nursing science research to support nursing care practice].
AB  - It is stated in this article that nursing is a professional science the goal
      being to utilize the nursing practice. New theories are formed or existing
      theoretical hypotheses are tested by nursing research. The difference between
      these two approaches is introduced. Nursing research for health promotion,
      prevention from illness and rehabilitation is discussed. The subject is viewed by
      the basic concepts of nursing: person, environment, health, nursing
      interventions. It seems to be essential to develop nursing theory for practise.
      It means to accept the point of view in which clinical nurses are theorists like
      academic researches.

PMID- 8260684
TI  - [Home care nurses' support of the relative caregiver of the patient dying at
      home].
AB  - The purposes of this article is to describe the need for support of the family
      members as care givers and the support they have received from domiciliary care
      team when caring for a dying family member at home. The article is based on the
      study which is one part of the STAKES research project called "Death with
      dignity". The project takes place in ten Finnish municipalities. This study was
      carried out in Tornio in August 1993 where eight family care givers were
      interviewed. The results show that the family care givers needed and had received
      both instrumental help and psychosocial support. The most important instrumental
      help was accurate information and guidance in practical skills e.g. how to use
      different kinds of instruments. The family care givers needed psychosocial
      support to be able to support the dying person. The interviewees emphasized
      particularly the value of hope both to the ill person and to the other family
      members. Trying to maintain hope after a terminal diagnosis is a lonely process
      for the patient and for the family, because for them, the health-care system
      often offers only bad news. The interviewees also underlined the need of official
      financial support system of the society.

PMID- 8260685
TI  - [Private sector completion and alternatives. Private home care nursing].
AB  - The status of private home care in health care area and how to prove high quality
      care are discussed in this article. The clients must have a possibility to make a
      decision to buy services based on real facts. That is why written nursing care
      plan and quality assurance are the main tools.

PMID- 8260687
TI  - [Care of urinary continence disorders].

PMID- 8260688
TI  - [Care of the feet in the elderly].

PMID- 8260686
TI  - [Discharge planning and continuity of care of the patient with stroke].
AB  - The discharge and continuity of care of the patient suffering circulatory
      disorders in brains are discussed in this article. In nursing care it is
      essential to draw attention to the following issues: active nursing care from the
      beginning of care emphasizing discharge, to inform the patient of the nursing
      care plan and implementation participation of the patient's family in the nursing
      care plan as early a stage as possible to settle the matters at home carefully
      (stairs, lift, thresholds, doors, floor material, toilet facilities,
      communication facilities etc.) good cooperation and information between the ward
      and the personnel in charge of the continuity of care in primary care services,
      social services and family equal, emphatic, individual and trustworthy attitude
      towards the patient and the family.

PMID- 8260689
TI  - [Future dreams of a traditional bedside care unit. Clinical nursing unit].
AB  - Clinical nursing unit is a new, innovative attempt to provide care for those who
      need high quality nursing temporarily as a means of achieving recovery. The unit
      is fundamentally different than a medical ward. The leader of the unit is a nurse
      and nursing is the main activity. The work is always multidisciplinary other
      healthcare professionals acting as consultants and working within the agreed
      philosophy. In this paper a short review of literature on the clinical nursing
      unit and its benefits are presented. Studies suggest that they are both feasible
      and beneficial alternatives to acute and community hospitals. Can such a unit
      become a part of reality in Finland is also discussed.

PMID- 8260690
TI  - [Multi-disciplinary team work in health services development].
AB  - Multidisciplinary teamwork or collaboration is a new approach designed to guide
      thinking and practise within healthcare systems. As a concept multidisciplinary
      collaboration or teamwork is not clear. Researchers have developed many
      definition about multidisciplinary collaboration having characteristics like
      objectivity, methodicalness, regularity, common goals, population's/patient's
      perspective and individually shared responsibility. In decision making every
      expert has a responsibility to give his/her skills and acknowledge for the goals
      of the working community and patients. A great deal of research and development
      work is currently ongoing in hospitals and health centers on multidisciplinary
      topic. This approach has been useful in district responsibility and also in
      primary nursing. The leadership in primary nursing system has the responsibility
      to create an environment conductive for collaborative relationships. In
      multiprofessional relationships nurses can find their professional roles and
      evaluate their skills and knowledge base and assess their needs for continued
      education.

PMID- 8260691
TI  - [Health care priorities].
AB  - This article describes the STAKES (National Research and Development Centre for
      Welfare and Health) Priorisation Project which started at the beginning of 1993.
      The project surveys ethical problems related to welfare and health care resource
      allocation. It searches for principles which could be applied in setting
      priorities whether they are aimed at service systems or individuals. A public
      debate has been instigated on choices, their justification and values which
      influence them. A conflict arises when medical advances have improved treatment
      possibilities and the needs have increased, but health care resources have
      remained on the same level or diminished. The role of nursing is to safeguard the
      rights of the patients. Now it is more important than ever to base nursing
      practice on ethical principles.

PMID- 8260692
TI  - Hematopoietic regulators: redundancy or subtlety?

PMID- 8260693
TI  - Absence of reverse transcription-polymerase chain reaction detectable residual
      disease in patients with acute promyelocytic leukemia in long-term remission.
AB  - Hybrid fusion genes are specific tumor markers of several leukemic subtypes. The
      use of reverse transcription-polymerase chain reaction (RT-PCR) to amplify
      chimeric cDNAs allows sensitive detection of the neoplastic clone for diagnostic
      and monitoring studies in these leukemias. Nonetheless, the clinical relevance of
      minimal residual disease (MRD) evaluation by PCR remains controversial. In this
      study, 9 patients (pts) with acute promyelocytic leukemia (APL) in long-term
      remission for 4 to 12 years were analyzed for the presence of MRD by RT-PCR
      amplification of the specific PML/RAR-alpha fusion gene. Seven pts had been
      treated with conventional chemotherapy (CHT) alone, 1 had undergone allogeneic
      bone marrow transplantation (BMT), and 1 autologous BMT as consolidation therapy
      after CHT. In 8 cases, the presence of the t(15;17) rearrangement could be
      documented in diagnostic BM specimens by cytogenetic and/or molecular analysis. A
      two-rounds "nested" RT-PCR assay with sensitivity levels of 1 in 10(5) was used
      to analyze BM samples collected at 32 to 141 months from the achievement of
      complete remission (CR). In no cases were residual PML/RAR-alpha transcripts
      detectable in these remission controls. All patients are in unmaintained CR at 48
      to 154 months from CR and at 6 to 17 months from PCR evaluation. These results
      suggest that long-term survival of APL is associated with eradication of cells
      carrying the specific PML/RAR-alpha rearrangement, indicating that PCR negativity
      should be considered the therapeutic goal in these patients. Our findings further
      strengthen the clinical relevance of PCR monitoring studies in APL, as opposite
      to other leukemic subtypes (chronic myeloid leukemia and acute myeloid leukemia
      M2) in which the prognostic significance of PCR evaluation is unclear.

PMID- 8260694
TI  - Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2)
      in acute promyelocytic leukemia.
AB  - It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100
      mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by
      a differentiation process. To date, ATRA dose-ranging studies have not yet been
      evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a
      lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with
      ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had
      failed after conventional first induction chemotherapy. Twenty-four of 30
      achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days.
      Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in
      9 patients between days 10 and 23. Clinical complications that may have been
      related to the retinoic acid syndrome were observed in 8 patients, of whom 3
      died. Pharmacokinetics studies were performed in 5 patients. Peak plasma
      concentrations and mean area under the concentration-time curve were not lower
      than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows
      that there is no difference in terms of therapeutic efficacy, triggering of
      hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with
      ATRA at 25 or 45 mg/m2/d.

PMID- 8260695
TI  - Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with an
      intensive epirubicin-containing regimen.
AB  - An intensive chemotherapy regimen (EVDAC), including high-dose epirubicin,
      vincristine, and dexamethasone followed by cyclophosphamide and high-dose
      cytarabine, was administered to 54 untreated adults with intermediate or high
      grade non-Hodgkin's lymphomas (NHL). The median age was 59, 61% were Ann Arbor
      Stage IV, 57% had "B" symptoms, 50% had serum lactate dehydrogenase greater than
      250 U/L, and 48% had masses greater than 7 cm (33% > 10 cm) in diameter. Seventy
      six percent of patients attained complete or probable complete remissions. The
      Kaplan-Meier actuarial failure-free survival at 7 years is 50%, and 59% (32 of
      54) of all patients started on therapy remain alive and in first remission at a
      median of 62+ (range, 49+ to 76+) months from completion of therapy. Nearly all
      patients developed severe neutropenia. Febrile episodes requiring hospitalization
      during neutropenia occurred after 56% of courses of epirubicin, vincristine, and
      dexamethasone and after 9% of courses of cyclophosphamide and cytarabine; 80% of
      patients were hospitalized at least once. Platelet count nadirs of less than
      20,000/microL occurred after only 1 of 146 evaluable courses of epirubicin and
      after none of the cyclophosphamide/cytarabine courses. Although 8 patients had
      decreases of at least 0.12 in their left ventricular ejection fractions (5 to
      below normal levels), none have developed clinically evident congestive heart
      failure. Clinically significant mucositis occurred after only 8% of courses of
      high-dose epirubicin. Three deaths from infections and one from hyperkalemia with
      cardiac arrest occurred during therapy. These results confirm that high remission
      and sustained, failure-free survival rates can be achieved in patients with
      aggressive NHL, using high-dose anthracycline-containing chemotherapy regimens.
      Epirubicin appears to have an advantage over doxorubicin at high doses because of
      decreased toxicity at a therapeutically equivalent dose. These phase II study
      results need to be validated in a randomized phase III trial, and growth factors
      should be used to attempt to reduce the neutropenia-associated complications.

PMID- 8260696
TI  - Additive effect of erythropoietin and heme on murine hematopoietic recovery after
      azidothymidine treatment.
AB  - The ability of combination treatment with erythropoietin (Epo) and heme to rescue
      hematopoietic activity in mice from the suppressive effect of azidothymidine
      (AZT) was determined. Exposure of mice to AZT for 5 weeks produced marked anemia,
      thrombocytopenia, neutropenia, and weight loss, whereas mice that received Epo
      and heme for 3 subsequent weeks showed significant alleviation of AZT
      cytotoxicity. Treatment with Epo (10 U for 5 times/week) stimulated hematopoietic
      recovery in the AZT-treated animals and reduced the severe anemia and
      thrombocytopenia by 3 weeks. Administration of a lower Epo dose (1 U Epo)
      resulted in only a modest retardation of AZT-induced anemia, although, when
      combined with heme, there was a great improvement in recovery of erythropoiesis.
      The combination of heme with Epo (10 U) produced the optimum response, resulting
      in almost normal recovery of bone marrow cellularity as well as recovery of burst
      forming units-erythroid (BFU-E) and splenic hematopoietic progenitor content
      (colony-forming unit-spleen [CFU-S]) by the end of 3 weeks of post-AZT treatment.
      Treatment with heme alone markedly enhanced the recovery of BFU-E and CFU-S, as
      well as body weight post-AZT; however, this recovery was not to the extent seen
      in combination with Epo (10 U). Long-term bone marrow cultures (LTBMCs)
      established from mice exposed to AZT for 8 weeks showed a marked reduction in
      cellularity and this was completely alleviated when mice received heme and Epo
      (10 U) for 3 weeks after 5 weeks of AZT administration. The additive effect of
      heme and Epo was seen in BFU-E production, as well as in CFU-S production, in
      LTBMCs. Thus, heme exerts a significant protective effect on hematopoietic
      progenitors in vivo and may be of potential clinical use in combination with Epo
      to promote effective erythropoiesis in the setting of AZT therapy.

PMID- 8260697
TI  - Characterization of a 5-fluorouracil-enriched osteoprogenitor population of the
      murine bone marrow.
AB  - In the presence of beta-glycerophosphate and vitamin C, cultures of normal mouse
      bone marrow cells form three-dimensional structures that stain positive with the
      Von Kossa technique and express alkaline phosphatase (ALP), collagen type I, and
      osteocalcin. Little is known about the characteristics and frequency of the cells
      that contribute to this phenomenon. Most likely, mature osteoblastic cells do not
      contribute to the nodule formation because no osteocalcin expressing cells are
      detected in the flushed marrow by in situ hybridization. Limiting dilution
      analysis shows that, in normal bone marrow, 1 of 2.2 x 10(5) cells has the
      potency to form a bone nodule and to express ALP, collagen, and osteocalcin in a
      temporal fashion. Upon in vivo treatment with 5-fluorouracil (5-FU), this
      frequency increases 12-fold, eg, 1 in 1.75 x 10(4) cells shows osteogenic
      activity. In comparison, fibroblast colony forming cells occur at a frequency of
      1 of 2.5 x 10(4) or 1 of 5 x 10(3) plated cells in normal or 5-FU-treated marrow,
      respectively. Using density centrifugation, the majority of the osteoprogenitor
      cells in 5-FU marrow are found in the low-density (1.066 to 1.067 g/mL)
      fractions. In addition, these cells bind to nylon wool but not to plastic and
      aggregate in the presence of wheat germ agglutinin and soybean agglutinin.
      Scanning and transmission electron microscopy shows that the bone nodules in 5-FU
      marrow cultures are composed of fibroblastoid cells embedded in a mineralized
      collagen matrix. In conclusion, our results show that a quiescent cell population
      in the murine bone marrow with fibroblastoid characteristics contributes to the
      formation of bone-like nodules in vitro.

PMID- 8260698
TI  - Effects of novel retinoic acid compound, 9-cis-retinoic acid, on proliferation,
      differentiation, and expression of retinoic acid receptor-alpha and retinoid X
      receptor-alpha RNA by HL-60 cells.
AB  - Retinoic acid modulates proliferation and differentiation of a wide variety of
      normal and leukemic cells through two distinct families of transcriptional
      factors: the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs).
      A stereoisomer of retinoic acid, 9-cis-retinoic acid, is a high-affinity ligand
      for RXR and binds efficiently to RAR. In contrast, all-trans-retinoic acid
      interacts 40-fold less efficiently with RXR as compared with RAR. To clarify the
      biologic role of retinoic acid compounds (all-trans,- 9-cis-, and 13-cis-retinoic
      acid) in hematopoietic cells, we studied their effects on clonal growth,
      differentiation, and expression of RAR-alpha and RXR-alpha genes in HL-60 cells.
      At very low concentrations (10(-15) to 10(-12) mmol/L), each retinoid enhanced
      clonal growth of HL-60 cells. These concentrations of the retinoids had no
      capacity to induce differentiation of leukemic cells as measured by ability
      either to reduce nitroblue tetrazolium and to express CD11b antigens, suggesting
      that retinoids at very low concentrations may stimulate proliferation of leukemic
      cells rather than induce their differentiation. These findings may help explain
      why patients with acute promyelocytic leukemia may relapse while receiving
      retinoic acids. With continuous therapy, retinoids are metabolized rapidly with
      increased urinary excretion, lowering their plasma levels to a range that may
      stimulate proliferation without inducing differentiation of leukemic cells. In
      contrast, we found that at higher concentrations (> or = 10(-11) mmol/L) each
      retinoid inhibited clonal growth, reduced c-myc RNA levels, and induced
      differentiation of HL-60 cells. 9-cis-retinoic acid was a slightly more potent
      inducer of differentiation than all-trans-retinoic acid; the mechanism for this
      increased potency and its clinical potential requires additional studies. Steady
      state levels of RAR-alpha mRNA in HL-60 cells were not affected by either 9-cis-
      and all-trans-retinoic acid. In contrast, 9-cis-retinoic acid, but not all-trans
      retinoic acid, reduced RXR-alpha mRNA accumulation in a dose-dependent manner.

PMID- 8260699
TI  - Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible
      factor 1 DNA-binding activity: implications for models of hypoxia signal
      transduction.
AB  - Erythropoietin (EPO) gene transcription is activated in kidney cells in vivo and
      in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia-inducible factor 1
      (HIF-1) is a nuclear factor that binds to the hypoxia-inducible enhancer of the
      EPO gene at a site that is required for transcriptional activation. HIF-1 DNA
      binding activity is induced by hypoxia or cobalt chloride treatment of Hep3B
      cells. We report that treatment of Hep3B cells with desferrioxamine (DFX) induced
      HIF-1 activity and EPO RNA expression with kinetics similar to the induction of
      HIF-1 by hypoxia or cobalt chloride. Induction by each of these stimuli was
      inhibited by cycloheximide, indicating a requirement for de novo protein
      synthesis. DFX appears to induce HIF-1 by chelating iron as induction was
      inhibited by coadministration of ferrous ammonium sulfate. DFX administration to
      mice transiently increased EPO RNA levels in the kidney. As previously shown for
      hypoxia and cobalt treatment, DFX also induced HIF-1 activity in non-EPO
      producing cells, suggesting the existence of a common hypoxia signal-transduction
      pathway leading to HIF-1 induction in different cell types.

PMID- 8260700
TI  - Macrophage colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor stimulate the synthesis of plasminogen-activator inhibitors by
      human monocytes.
AB  - Macrophage colony-stimulating factor (M-CSF or CSF-1) and granulocyte-macrophage
      CSF (GM-CSF) have been shown to increase human monocyte urokinase-type
      plasminogen-activator (u-PA) activity with possible consequences for cell
      migration and tissue remodeling; because monocyte u-PA activity is likely to be
      controlled in part also by the PA inhibitors (PAIs) made by the cell, the effect
      of M-CSF and GM-CSF on human monocyte PAI-2 and PAI-1 synthesis was investigated.
      To this end, elutriation-purified human monocytes were treated in vitro with
      purified recombinant human M-CSF and GM-CSF, and PAI-2 and PAI-1 antigen and mRNA
      levels measured by specific enzyme-linked immunosorbent assays and Northern blot,
      respectively. Each CSF could enhance the protein and mRNA levels of PAI-2 and PAI
      1 at similar concentrations for each product. This similar regulation of monocyte
      PAI expression in response to the CSFs contrasted with that found for the effects
      of lipopolysaccharide, transforming growth factor-beta and a glucocorticoid.
      Therefore, PAIs may be modulating the effects of the CSFs on monocyte u-PA
      activity at sites of inflammation and tissue remodeling.

PMID- 8260701
TI  - Role of plasminogen activator inhibitor-1 in promoting fibrin deposition in
      rabbits infused with ancrod or thrombin.
AB  - The role of defective fibrinolysis caused by elevated activity of plasminogen
      activator inhibitor-1 (PAI-1) in promoting fibrin deposition in vivo has not been
      well established. The present study compared the efficacy of thrombin or ancrod,
      a venom-derived enzyme that clots fibrinogen, to induce fibrin formation in
      rabbits with elevated PAI-1 levels. One set of male New Zealand rabbits received
      intravenous endotoxin to increase endogenous PAI-1 activity followed by a 1-hour
      infusion of ancrod or thrombin; another set of normal rabbits received
      intravenous human recombinant PAI-1 (rPAI-1) during an infusion of ancrod or
      thrombin. Thirty minutes after the end of the infusion, renal fibrin deposition
      was assessed by histopathology. Animals receiving endotoxin, rPAI-1, ancrod, or
      thrombin alone did not develop renal thrombi. All endotoxin-treated rabbits
      developed fibrin deposition when infused with ancrod (n = 4) or thrombin (n = 6).
      Fibrin deposition occurred in 7 of 7 rabbits receiving both rPAI-1 and ancrod and
      in only 1 of 6 receiving rPAI-1 and thrombin (P < .01). In vitro, thrombin but
      not ancrod was inactivated by normal rabbit plasma and by purified antithrombin
      III or thrombomodulin. The data indicate that elevated levels of PAI-1 promote
      fibrin deposition in rabbits infused with ancrod but not with thrombin. In
      endotoxin-treated rabbits, fibrin deposition that occurs with thrombin infusion
      may be caused by decreased inhibition of procoagulant activity and not increased
      PAI-1 activity.

PMID- 8260702
TI  - Coordinated inhibition of actin-induced platelet aggregation by plasma gelsolin
      and vitamin D-binding protein.
AB  - Actin is an abundant intracellular protein that is released into the blood during
      tissue injury and its injection into rats causes microthrombi to form in the
      vasculature. This report and others have shown that actin filaments are able to
      aggregate platelets in an adenosine diphosphate (ADP)-dependent manner. The
      effects on this process of two plasma actin-binding proteins, vitamin D-binding
      protein (DBP) and gelsolin, were examined separately and together. The addition
      of DBP, a monomer-binding protein, to actin filaments did not affect their
      ability to induce platelet aggregation. However, severing of actin filaments with
      gelsolin resulted in an increased degree of platelet aggregation. Preincubation
      of F-actin with both gelsolin and DBP resulted in a significant inhibition of
      aggregation. The effects of DBP and gelsolin on actin-induced aggregation
      paralleled their effects on exchange of actin-bound adenine nucleotides. DBP
      inhibited 1, N6-ethenoadenosine 5' triphosphate (epsilon-ATP) exchange with G
      actin but not with F-actin. Gelsolin increased epsilon-ATP exchange with F-actin,
      which was largely abrogated by the addition of DBP. These results suggest that
      gelsolin's severing (and subsequent capping) of actin filaments not only results
      in an increase in the number of pointed filament ends but also in the
      dissociation of actin monomers containing ADP. Phalloidin, which stabilizes actin
      filaments while decreasing both monomer and nucleotide exchange, inhibited actin
      induced aggregation, as well, indicating that depolymerization of actin filaments
      is not required to inhibit aggregation. Platelet activation by either G- or F
      actin may thus be regulated by the local concentrations of the plasma actin
      binding proteins gelsolin and DBP. Together, these proteins inhibit platelet
      aggregation in a manner that can be explained by their effects on actin's
      filament structure and the accessibility of its bound ADP. Depletion of DBP or
      gelsolin may allow actin released from injured tissues to stimulate purinergic
      receptors on platelets, and perhaps other cells, via its bound adenine
      nucleotides.

PMID- 8260703
TI  - Prophylaxis against a Melanesian variant of human T-lymphotropic virus type I
      (HTLV-I) in rabbits using HTLV-I immune globulin from asymptomatically infected
      Japanese carriers.
AB  - Molecular variants of human T-lymphotropic virus type I (HTLV-I), which diverge
      significantly from the so-called cosmopolitan prototypes, have been discovered in
      Melanesia. In this study, HTLV-I IgG (I-IgG) prepared from seropositive healthy
      Japanese carriers was evaluated for its protective effect against a Melanesian
      isolate, HTLV-IMEL5, in rabbits. Normal IgG (N-IgG) prepared from seronegative
      healthy Japanese was used as control. Both preparations contained 50 mg/mL of IgG
      and I-IgG had a high neutralizing antibody titer, as determined by vesicular
      stomatitis virus--HTLV-I pseudotype assay. Of four experimental groups (A, B, C,
      and D), each with three rabbits, groups A and B were infused with 10 mL of N-IgG
      and I-IgG, respectively, and animals were challenged immediately by transfusion
      of 5 mL of blood from a rabbit infected with HTLV-IMEL5. Animals in groups C and
      D were immunized with 10 mL of I-IgG 24 and 48 hours, respectively, after being
      transfused with 5 mL of blood from the virus-infected rabbit. HTLV-I infection,
      as determined by seroconversion and verified by polymerase chain reaction,
      occurred in all rabbits in groups A and D after 2 to 6 weeks, but in none of the
      animals in groups B and C. These data indicate that I-IgG is protective against
      HTLV-IMEL5 infection when administered before or within 24 hours of transfusion
      with virus-contaminated blood. Moreover, our study shows that the neutralizing
      domains of the so-called cosmopolitan and Melanesian strains of HTLV-I are
      functionally indistinguishable.

PMID- 8260704
TI  - Interleukin-1 receptor antagonist blocks chemokine production in the mixed
      lymphocyte reaction.
AB  - The mixed lymphocyte reaction (MLR) has previously been used to elucidate
      pathways of cytokine activation and T-lymphocyte proliferation and is regarded as
      a model that simulates responses in allograft rejection. Studies have indicated
      that interleukin-1 (IL-1), a potent inflammatory cytokine, may have an important
      activating role in the MLR response. The discovery of a naturally occurring IL-1
      receptor antagonist protein (IRAP) has renewed interest in control of IL-1-
      dependent responses both in vitro and in vivo. MLR cultures were used to study
      the role of IL-1 and IRAP in the regulation of subsequent cytokines during a T
      lymphocyte-mediated alloantigen response. The temporal expression of IL-1 and
      IRAP during 5-day one-way MLR assays suggested antagonistic production of the two
      cytokines. IL-1 was produced early in the response, peaking at 4 hours through
      day 2, subsequently declining to near-background levels on day 5 of culture. In
      contrast, production of IRAP was delayed until day 2, steadily increased on days
      3 and 4, and peaked on day 5 of culture, which correlated with the declining
      levels of IL-1. The addition of graded doses of IRAP (25 to 1,000 ng/mL) to MLR
      cultures decreased IL-1 production but had no effect on T-lymphocyte
      proliferative response. In addition, IRAP had little effect on the production of
      either IL-2 or tumor necrosis factor. The addition of 25 ng/mL of IRAP to MLR
      assays showed significantly decreased levels of two potent chemotactic cytokines,
      IL-8 and macrophage inflammatory protein-1 alpha (MIP-1 alpha), at peak chemokine
      production on day 5 of culture. The levels of IL-8 and MIP-1 alpha could be
      restored by the addition of IL-1 to the IRAP-treated cultures. IL-8 and MIP-1
      alpha represent the two different families of chemotactic cytokines, C-X-C (IL-8)
      and C-C (MIP-1 alpha), and potentially play important roles in the recruitment of
      leukocytes to a site of immune allogeneic response. These studies indicate that
      regulation of IL-1 by IRAP does not significantly reduce T-lymphocyte activation
      but can regulate the production of chemokines involved in leukocyte recruitment.

PMID- 8260705
TI  - Transduction of human melanoma cell lines with the human interleukin-7 gene using
      retroviral-mediated gene transfer: comparison of immunologic properties with
      interleukin-2.
AB  - Two human melanoma cell lines were transduced with the human interleukin (IL)-7
      and IL-2 genes using retroviral-mediated gene transfer. Stable, high-level
      cytokine expression was achieved. The in vitro growth of transduced tumors was
      unaltered. Neither of the IL-2-transduced melanoma cell lines grew in athymic
      mice, whereas one IL-7-transduced melanoma line showed retarded in vivo growth.
      This is consistent with animal studies suggesting a predominantly T-cell response
      to IL-7-transduced tumors and a more nonspecific response to IL-2-transduced
      tumors. Both IL-7- and IL-2-transduced melanoma cell lines could induce cytotoxic
      lymphocytes in mixed lymphocyte-tumor cultures. The expression of putative
      melanoma antigens (MAGE)-1 and MAGE-3 was unaltered by cytokine transduction. In
      one cell line, IL-7 transduction resulted in a marked inhibition of the
      immunosuppressive peptide transforming growth factor (TGF)beta 1. The results
      allow a comparison of immunobiologic properties of IL-7- and IL-2-transduced
      human melanoma cell lines in consideration of their use in genetically engineered
      tumor vaccines. IL-7 transduction results in stable cytokine expression and
      phenotypic alterations that appear to be favorable for enhanced immunogenicity
      and it deserves clinical testing.

PMID- 8260706
TI  - Infection of peripheral blood mononuclear cells by hepatitis C virus in mixed
      cryoglobulinemia.
AB  - A striking association between hepatitis C virus (HCV) infection and mixed
      cryoglobulinemia (MC) has been shown; thus, HCV seems to play an important
      etiopathogenetic role in this lymphoproliferative disorder. Because HCV is both a
      hepatotropic and lymphotropic virus, this study aimed to investigate the
      prevalence of HCV infection of peripheral blood mononuclear cells (PBMCs) in a
      series of 16 patients with type II (IgMk) MC. Antibodies against HCV were
      detected by commercially available kits (Second Generation Chiron enzyme-linked
      immunosorbent assay [ELISA] and recombinant-based immunoblot assay [RIBA]), and
      the presence of HCV RNA was evaluated in both sera and isolated PBMCs using the
      polymerase chain reaction technique. A previous exposure to HCV was shown by
      ELISA and confirmed by RIBA in all cases (100%). Moreover, HCV RNA was present in
      the sera of 8 of 16 patients (50%), whereas its frequency markedly increased (13
      of 16 [81%]) when genomic sequences were detected in peripheral lymphocytes. HCV
      RNA was never detected in the PBMCs of 20 control subjects. These findings showed
      that HCV infection, alone or in combination with other factors, may be
      responsible for the clonal B-cell expansion underlying the systemic
      manifestations of MC, and may explain the appearance of a malignant non-Hodgkin's
      lymphoma in some subjects.

PMID- 8260707
TI  - Rearrangements of the MLL gene in therapy-related acute myeloid leukemia in
      patients previously treated with agents targeting DNA-topoisomerase II.
AB  - Chromosome band 11q23 is frequently involved in acute myeloid leukemia (AML) and
      acute lymphoblastic leukemia (ALL) de novo, as well as in myelodysplastic
      syndromes (MDS) and lymphoma. Five percent to 15% of patients treated with
      chemotherapy for a primary neoplasm develop therapy-related AML (t-AML) that may
      show rearrangements, usually translocations involving band 11q23 or, less often,
      21q22. These leukemias develop after a relatively short latent period and often
      follow the use of drugs that inhibit the activity of DNA-topoisomerase II (topo
      II). We previously identified a gene, MLL (myeloid-lymphoid leukemia or mixed
      lineage leukemia), at 11q23 that is involved in the de novo leukemias. We have
      studied 17 patients with t-MDS/t-AML, 12 of whom had cytogenetically detectable
      11q23 rearrangements. Ten of the 12 t-AML patients had received topo II
      inhibitors and 9 of these, all with balanced translocations of 11q23, had MLL
      rearrangements on Southern blot analysis. None of the patients who had not
      received topo II inhibitors showed an MLL rearrangement. Of the 5 patients
      lacking 11q23 rearrangements, some of whom had monoblastic features, none had an
      MLL rearrangement, although 4 had received topo II inhibitors. Our study
      indicates that the MLL gene rearrangements are similar both in AML that develops
      de novo and in t-AML. The association of exposure to topo II-reactive
      chemotherapy with 11q23 rearrangements involving the MLL gene in t-AML suggests
      that topo II may play a role in the aberrant recombination events that occur in
      this region both in AML de novo and in t-AML.

PMID- 8260708
TI  - Adhesion of human myeloma-derived cell lines to bone marrow stromal cells
      stimulates interleukin-6 secretion.
AB  - Previous studies show that human myeloma-derived cell lines specifically adhere
      to fibronectin (FN) through very late antigen-4 (VLA-4; alpha 4 beta 1 integrin
      complex) and RGD-peptide mechanisms, which may contribute to the localization of
      tumor cells in bone marrow (BM). In these studies, we characterized the adhesion
      of myeloma-derived cell lines to both normal and myeloma BM stromal cells (BMSCs)
      and the effect of adhesion on DNA synthesis. Because interleukin-6 (IL-6) plays
      an important role in the pathogenesis of multiple myeloma, we also examined the
      effects of tumor cell adhesion on IL-6 secretion by BMSCs. In 51chromium binding
      assays, the U266, ARH-77, and IM-9 cell lines showed 52% +/- 12%, 55% +/- 6%, and
      47% +/- 7% specific adherence, respectively, to normal BMSCs and 74% +/- 4%, 60%
      +/- 3%, and 61% +/- 6% specific adherence, respectively, to myeloma BMSCs. In
      contrast, only 12% to 13% specific binding of HS-Sultan cells to BMSCs was noted.
      The binding of myeloma cells to BMSCs was partially blocked with anti-beta 1
      monoclonal antibody (MoAb), anti-beta 2 integrin MoAb, and excess RGD peptide,
      suggesting multiple mechanisms for the adhesion of myeloma cell lines to BMSCs.
      Binding of cell lines to FN or myeloma BMSCs did not affect cell line
      proliferation; however, adhesion of myeloma cell lines to normal BMSCs decreased
      DNA synthesis, ie, stimulation indices are 0.1 +/- 0.04, 0.2 +/- 0.1, 0.2 +/-
      0.07, and 0.1 +/- 0.06 for the adherent non-IL-6-dependent U266, ARH-77, HS
      Sultan, and IM-9 cells, respectively (n = 5, P < .01). In contrast, adherence of
      IL-6-dependent B9 cells increased their proliferation (stimulation index, 3.2 +/-
      0.7). Significant (twofold to eightfold) increases in IL-6 secretion were evident
      in cell line-adherent (> or = 12 hours) normal and myeloma BMSC cultures.
      Paraformaldehyde fixation of BMSCs before adhesion completely abrogated IL-6
      secretion, suggesting that IL-6 secretion was triggered in BMSCs rather than in
      cell lines. Partial blocking of cell line adhesion to BMSCs, using anti-beta 1
      integrin and anti-beta 2 integrin MoAbs and RGD peptide, also partially blocked
      the triggering of IL-6 secretion by BMSCs. When cell lines were placed in
      Transwell inserts and then cultured with either normal or myeloma BMSCs,
      permitting juxtaposition without cell to cell contact between myeloma cell lines
      and BMSCs, no increase in IL-6 secretion was observed.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8260709
TI  - Heterogeneous expression of a novel MPC-1 antigen on myeloma cells: possible
      involvement of MPC-1 antigen in the adhesion of mature myeloma cells to bone
      marrow stromal cells.
AB  - Recent immunophenotypic analysis has shown that the heterogeneous expression of
      the adhesion molecule VLA-5 classifies myeloma cells into VLA-5+ mature and VLA-5
      immature subpopulations. To further clarify the two myeloma subpopulations, we
      generated a monoclonal antibody, MPC-1, by immunizing mice with an adherent human
      myeloma cell line, KMS-5. The MPC-1 antibody recognized a 48-Kd surface antigen
      on KMS-5 but not on U-266, a nonadherent human myeloma cell line. Specificity
      characterization showed that MPC-1 antigen was expressed on mature myeloma cells,
      normal plasma cells, and mature B cells, whereas pre-B cells and germinal center
      B cells lacked its expression. Monocytes and a human bone marrow stromal cell
      line, KM102, also expressed this antigen. Two subclones of MPC-1+ VLA-5+ (KMS
      5Ad) and MPC-1-VLA-5+ (KMS-5NAd) were separated from the KMS-5 cell line. The KMS
      5NAd adhered to KM102 more tightly than did the KMS-5NAd, and the U-266 (MPC-1
      VLA-5-) displayed almost no adherence to the KM102. The adhesion of the KMS-5Ad
      was partially inhibited by the MPC-1 antibody. These results, taken together,
      suggest that the MPC-1 antigen serves as a differentiation marker for B-lineage
      cells, including plasma cells, and may function as an adhesion molecule involved
      in the interaction of mature myeloma cells with bone marrow stromal cells.

PMID- 8260710
TI  - Results of intensive therapy in childhood acute myeloid leukemia, incorporating
      high-dose melphalan and autologous bone marrow transplantation in first complete
      remission.
AB  - Childhood acute myeloid leukemia (AML) has a poor prognosis with standard
      chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves
      the outlook only for the one third of patients with sibling donors. Autologous
      BMT with a lower morbidity and mortality is available to all. In this study,
      maximum cytoreduction was achieved by intensive early chemotherapy. Final
      intensification, with autologous BMT was offered to all those remaining in first
      complete remission (CR). Patients received two induction and two consolidation
      courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day
      14 and remission was assessed after courses 2 and 4. Bone marrow was harvested
      after recovery from the second consolidation course or after the first
      maintenance course and separated on a discontinuous percoll gradient before
      cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR.
      Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty
      three patients received high-dose melphalan and 1 received busulphan and
      cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301)
      after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to
      greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92)
      after autologous BMT. Platelet recovery was delayed, with a median time to
      achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum
      follow up of 25 months following autologous BMT only 3 children have relapsed.
      The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence
      interval, 46% to 90%). Five-year EFS following autologous BMT is 87% (95%
      confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan
      administration after intensive chemotherapy has produced EFS equivalent to
      allogeneic BMT and is associated with a strikingly low relapse rate. High-dose
      melphalan appears to be a valuable agent for conditioning therapy in AML.

PMID- 8260711
TI  - Regulation of AP-1 expression and activity in antigen-stimulated mast cells: the
      role played by protein kinase C and the possible involvement of Fos interacting
      protein.
AB  - We have recently observed that protein kinase C (PKC) was involved in the
      regulation of the accumulation of mRNAs of the AP-1 components in cultured
      Abelson-transformed murine fetal-liver-derived mast cells stimulated by
      exocytotic stimuli. Here we analyzed the probable regulatory effect of PKC on the
      synthesis and DNA-binding activity of AP-1 complexes in immunologic stimulated
      mast cells. In this study we used the interleukin-3--dependent murine fetal-liver
      -derived mast cells that were not transformed by the Abelson oncogene. Study of
      PKC-depleted cells showed PKC dependency of c-fos mRNA accumulation and protein
      expression in IgE-Ag stimulated cells. In contrast, the c-jun mRNA accumulation
      was unaffected by PKC depletion, whereas its protein expression was dependent on
      this enzymatic activity. This suggests the involvement of PKC in the regulation
      of translation of c-Jun, a level of c-Jun regulation that was not previously
      described. The amount of AP-1 DNA-bound complex was also lowered in PKC-depleted
      cells. Therefore, PKC plays an important regulatory role in different stages of
      the signal transduction pathway because of IgE-Ag stimulation. Surprisingly, we
      have observed that although the amount of total synthesized c-Fos began to
      increase 15 minutes after immunologic stimulation, the amount of c-Fos associated
      with Juns did not increase, even after 45 minutes. This association was not
      affected by PKC. Using a Fos-interacting protein (FIP)-cDNA probe, an expression
      of 2.9 kb mRNA was detected in these cells. Furthermore, immunologic stimulation
      caused an increase in the amount of a Fos-containing protein complex that bound
      to an FIP-binding DNA oligonucleotide. Therefore, we propose that this protein
      complex that contains most of the immunologically induced c-Fos has an important
      role in IgE-Ag-stimulated signal transduction.

PMID- 8260712
TI  - Alteration in cytoadherence and rosetting of Plasmodium falciparum-infected
      thalassemic red blood cells.
AB  - Hemoglobinopathies have a protective role in malaria that appears to be related
      to alterations in red blood cell (RBC) properties. Thalassemic RBCs infected with
      Plasmodium falciparum showed greatly reduced cytoadherence and rosetting
      properties as well as impaired growth and multiplication. A significant decrease
      in the levels of falciparum antigens associated with the membrane of infected
      beta-thalassemic RBCs was observed at trophozoite/schizont stage, but not young
      ring stage. This reduction was shown when a cytoadherence inhibitory monoclonal
      antibody, but not a noninhibitory pooled immune serum, was used. These
      observations suggest that protection against malaria in thalassemia is caused by
      both reduced parasitemias and altered adherence properties of the infected
      thalassemic RBCs that promote enhanced clearance of the parasite from the
      circulation.

PMID- 8260713
TI  - Transcriptional and posttranscriptional regulation of the expression of the
      erythropoietin receptor gene in human erythropoietin-responsive cell lines.
AB  - With erythroid differentiation, committed progenitor cells acquire the ability to
      respond to erythropoietin (Epo). Epo interacts with target cells through the Epo
      receptor (Epo-R), whose expression is tightly regulated in a lineage-specific
      fashion. Epo-R expression is presumed to be progressively activated or repressed
      as cells progress along the erythroid or the myeloid pathway, respectively.
      Little is known of the mechanisms that underlie the erythroid-specific expression
      of the Epo-R gene. GATA-1, the major known transcription factor involved in Epo-R
      gene regulation, is not erythroid-specific. We have studied the regulation of the
      expression of the Epo-R gene in two related human Epo-responsive cell lines, UT-7
      and UT-7 Epo. These lines express Epo-R at high levels because of amplification
      of the endogenous gene, which is apparently not rearranged. Treatment for 6 to 24
      hours with the tumor promoter, phorbol myristate acetate (PMA), or 24 hours of
      growth factor starvation (Epo or granulocyte/macrophage colony-stimulating factor
      [GM-CSF]) decreased or increased the levels of Epo-R mRNA, respectively. In the
      case of growth factor starvation, the increase (approximately equal to threefold)
      in the level of Epo-R mRNA correlated directly with an increase in the rate of
      Epo-R gene transcription as measured by run-off assay. Both increases were
      observed as early as 3 hours after the growth factor was withdrawn and were
      reversible; levels of mRNA and transcription rates returned to baseline 3 hours
      after the cells were reexposed to growth factors. The changes in Epo-R expression
      after growth factor starvation were coordinated with changes in the level of
      expression of GATA-1 that were detected both at the mRNA and at the gene
      transcription level under these conditions (suggesting that GATA-1 was
      responsible for this upregulation). During PMA treatment, after a transient
      increase in Epo-R mRNA at 1 hour, a progressive decline in the level of Epo-R
      mRNA was observed; the level of Epo-R mRNA decreased by 50%, and fell below the
      level of detection by 6 and 24 hours, respectively. This decrement was explained
      in part by a fourfold reduction in the rate of gene transcription as well as a
      reduction (measured as levels of Epo-R mRNA in the presence of actinomycin D) in
      mRNA stability. The changes in transcription rate occurred in the absence of
      changes in the level of GATA-1 binding activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8260714
TI  - Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic
      T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism
      that is dependent on direct cell-cell contact.
AB  - HLA-identical bone marrow transplantation (BMT) may be complicated by graft
      versus-host disease or graft rejection. Both complications are thought to be
      initiated by recognition of minor histocompatibility (mH) antigens by HLA
      restricted mH-antigen-specific T lymphocytes. Using HLA-A2-restricted mH antigens
      HA-1-, -2-, and -4-, and HY-specific cytotoxic T lymphocyte (CTL) clones, we
      studied the recognition by these CTL clones of interleukin-2 (IL-2)-stimulated T
      cells (IL-2 blasts), BM mononuclear cells (BMMNCs), and hematopoietic progenitor
      cells (HPCs). We showed that, when IL-2 blasts from the BM donors who were
      investigated were recognized by the HA-1-, -2-, and -4-, and HY-specific CTL
      clones, their BMMNCs and HPCs were recognized as well by these CTL clones,
      resulting in antigen-specific growth inhibition of erythrocyte burst-forming
      units (BFU-E), colony-forming units-granulocyte (CFU-G), and CFU-macrophage (CFU
      M). the HA-2-specific CTL clone, however, inhibited BFU-E and CFU-G growth from
      four donors to a lesser extent than from two other donors. We further
      investigated whether inhibitory cytokines released into the culture medium by the
      antigen-specific stimulated CTLs or by stimulated BMMNCs were responsible for
      suppression of HPC growth or whether this effect was caused by direct cell-cell
      contact between CTLs and HPCs. HPC growth inhibition was only observed after
      preincubation of BMMNCs and CTLs together for 4 hours before plating the cells in
      semisolid HPC culture medium. When no cell-cell contact was permitted before
      plating, neither antigen-stimulated CTL nor antigen-nonstimulated CTLs provoked
      HPC growth inhibition. Culturing BMMNCs in the presence of supernatants harvested
      after incubation of BMMNCs and CTL clones together for 4 or 72 hours did also not
      result in HPC growth inhibition. Both suppression of HPC growth and lysis of IL-2
      blasts and BMMNCs in the 51Cr-release assay appeared to be dependent on direct
      cell-cell contact between target cells and CTLs and were not caused by the
      release of inhibitory cytokines into the culture medium by antigen-specific
      stimulated CTLs or by stimulated BMMNCs. Our results show that mH-antigen
      specific CTLs can inhibit HPC growth by a direct cytolytic effect and may
      therefore be responsible for BM graft rejection after HLA-identical BMT.

PMID- 8260715
TI  - Hemolysis after high-dose intravenous Ig.

PMID- 8260716
TI  - A deficiency in CDw52 (CAMPATH-1 antigen) of paroxysmal nocturnal hemoglobinuria
      lymphocytes.

PMID- 8260717
TI  - Isolation and characterization of a DNA fragment containing various kinds of
      repetitive sequences located on human chromosome 21.
AB  - In order to investigate the repetitive sequences located on human chromosome 21,
      we have isolated DNA fragments containing Alu sequences. One of the clones, p1,
      was chosen for further study, because it contained repetitive sequences different
      from the Alu sequence. Nucleotide sequence analysis of p1 indicates that p1
      contains L1 and O-family sequences. Interestingly, when the L1 sequence was used
      as a probe, a discrete band of 5 kb was seen in HindIII-digested DNA from somatic
      cell hybrids containing human chromosome 21 as the sole human chromosome. The L1
      sequence was rearranged and was interrupted by O-family sequence, which was
      flanked by 6 bp target site duplications. Since all three repetitive sequences
      are known to act as retroposons, these results imply that there is an integration
      hot spot on human chromosome 21. The sequence was mapped within 21q11-21.

PMID- 8260718
TI  - Detection of monosomy 7 by fluorescence in situ hybridization in acute
      nonlymphocytic leukemia and myelodysplastic syndrome.
AB  - Fluorescence in situ hybridization (FISH) with a chromosome 7 specific alpha
      satellite DNA probe was used to detect monosomy 7 in interphase and metaphase
      cells obtained from patients with myelodysplastic syndrome (MDS) and acute
      nonlymphocytic leukemia (ANLL). Chromosome analysis revealed monosomy 7, either
      alone or as part of a complex chromosome abnormality, in all cell samples. FISH
      analyses of 12 marrow samples and a blood sample using a chromosome 7 specific
      alpha satellite DNA probe revealed a single fluorescence spot in 80.5-97.5% of
      interphase cells indicating monosomy 7. In contrast, 83.5-92.0% of the same cells
      had two copies of chromosome 17 as two fluorescent spots were detected using a
      chromosome 17 specific alpha satellite DNA probe used as a positive control. The
      proportion of interphase cells with monosomy 7 did not correlated with the
      percentage of metaphase cells with monosomy 7 detected by conventional
      karyotyping or with the percentage of blast cells in the bone marrow.

PMID- 8260719
TI  - Cosmid clones from microdissected human chromosomal region 15q11-q13.
AB  - A human chromosomal region, 15q11-q13, was microdissected, its DNA was amplified
      with the primer-linker PCR method, and the PCR products were cloned into a
      plasmid vector to construct a microclone library. Of 193 microclones analyzed
      with Southern blot hybridization on hybrid cell panels, 26 (13.5%) were either
      single-copy (unique) or low-repetitive fragments. By screening of a cosmid
      library of human genomic DNA using the 26 microclones as probes, 47 positive
      cosmids were obtained and underwent regional mapping with chromosome fluorescence
      in situ hybridization (FISH). Sixteen cosmids gave FISH signals at 15p-cen, 5 at
      15q11-q13, 6 at 15q22-q26, 3 at other chromosomes, and 17 no signal. These 27
      cosmids mapped to chromosome 15 are useful additions to the inventory of DNA
      markers of this chromosome including the much interested Prader-Willi/Angelman
      syndrome region.

PMID- 8260720
TI  - Sexing of in vitro-fertilized preimplantation mouse embryos by the PCR method.
AB  - The applicability of the dual PCR method to embryo sexing was examined with the
      aim of establishing a noninvasive method of preimplantation diagnosis for human
      genetic disorders. Mouse pre-embryos obtained by in vitro fertilization were
      studied. The Sry gene sequence and the myogenin sequence were amplified as the Y
      specific and internal control sequences, respectively. Amplification of as little
      as 10 pg of mouse genomic DNA was possible with the dual PCR method, the
      sensitivity being 10-fold greater than that of the single PCR method. The sex was
      identified in 100% (24/24) and 96% (23/24) of the pre-embryos tested at the 16-
      and 4-cell stages, respectively. In addition, the sex of all four single
      blastomeres dissociated from 4-cell pre-embryos agreed in 76% (16/21) of the
      specimens tested and 94% (79/84) of dissociated blastomeres could be sexed. The
      sex of single blastomeres biopsied from pre-embryos at the 8-cell stage could be
      identified. After transfer of 13 male and 25 female sexed pre-embryos, six viable
      fetuses were obtained. Histological examination showed that all these fetuses
      were of the predicted sex. Sexing of biopsied single blastomeres by the dual PCR
      method was rapid and reliable, suggesting its feasibility for preimplantation
      diagnosis of in vitro fertilized human pre-embryos.

PMID- 8260721
TI  - Genetic polymorphism of orosomucoid (ORM) in populations of the United Kingdom,
      Indian subcontinent, and Cambodia.
AB  - The genetic variation of the human serum orosomucoid (ORM) was investigated by
      isoelectric focusing (IEF) followed by immunofixation in 15 different populations
      from East Midlands (United Kingdom), India, Sri Lanka, and Cambodia.
      Statistically significant differences were observed between various Asiatic and
      British populations, however differences within Asiatic and European populations
      were minor. The distribution of ORM1 alleles in populations investigated to date
      suggests an interesting east-west geographical cline. There is a suggestion that
      present day wide polymorphism at the ORM1 locus may be influenced by selection.

PMID- 8260722
TI  - Study of enzyme polymorphism and haemoglobin patterns amongst sixteen tribal
      populations of central India (Orissa, Madhya Pradesh, and Maharashtra).
AB  - A survey was conducted to study the genetic differentiation among 16 tribal
      groups of Orissa, Madhya Pradesh, and Maharashtra belonging to different ethnic
      and linguistic affiliations. Sixteen hundred and fifteen blood samples from both
      sexes were tested for 5 red cell enzyme systems: ACP, ESD, PGD, GLO, LDH, and Hb
      pattern. Three hundred and nineteen male individuals were tested for G-6-PD
      enzyme deficiency. The distribution of the enzyme markers and Hb show a range of
      variation which are more or less within the Indian range. Cases of homozygous
      HbSS were detected in all the tribes except 3 tribes in Orissa. Two cases of LDH
      Cal-1 homozygote were found in two Dravidian language speaking Orissa tribes. The
      chi 2-values for testing the homogeneity of gene frequencies indicate a non
      significant heterogeneity for all alleles in the individual system. Within
      population diversity seems to be larger than between population diversity. The
      degree of over all genetic differentiation as measured by GST value is 0.0154 +/-
      0.0071.

PMID- 8260723
TI  - Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion
      of chromosome 5.
AB  - A male infant with partial monosomy 5p and partial trisomy 5q due to paternal
      pericentric inversion of chromosome 5 (46,XY,rec(5), dup q,inv(5)(p15.1q35.1)pat)
      is reported together with the oral findings. The phenotype was chiefly the cri-du
      chat syndrome. Severe retardation of mental and motor development,
      microencephaly, cardiac malformation, crying and facial appearance unique to the
      cri-du-chat syndrome were observed. Perioral and intraoral findings included thin
      upper lip, down-turning corners of mouth, micrognathia, shallow palate, and cleft
      of soft palate. Anterior deciduous teeth were small and canine deciduous teeth
      were conic. The row of deciduous teeth showed a flat arch-like shape that was
      very wide but short in length. No abnormality was noted in the number of
      deciduous teeth or the timing of eruption.

PMID- 8260724
TI  - Ethics and fetal medicine.
AB  - Ethical issues in the clinical practice of fetal medicine are discussed, largely
      from the point of view of early prenatal medicine. The discussion concentrates on
      several aspects including the time when human life begins, the pros and cons of
      fetal medicine, and ethical guidelines for fetal medicine. The emphasis is placed
      on the importance of informed consent and an increase in genetical knowledge
      amongst the general public.

PMID- 8260725
TI  - Pericentric inversion in homologues of chromosome 9.

PMID- 8260726
TI  - Origin of the adjacent 1 disjunction.

PMID- 8260727
TI  - William L. McGuire Memorial Symposium. Estrogen receptors: ligand discrimination
      and antiestrogen action.
AB  - We have used affinity labeling, site-directed mutagenesis and regional chemical
      mutagenesis in order to determine regions of the estrogen receptor (ER) important
      in hormone binding, ligand discrimination between estrogens and antiestrogens,
      and transcriptional activation. Affinity labelling studies with the antiestrogen,
      tamoxifen aziridine and the estrogen, ketononestrol aziridine have identified
      cysteine 530 in the ER hormone binding domain as the primary site of labeling. In
      the absence of a cysteine at 530 (i.e. Cys530A1a mutant), C381 becomes the site
      of estrogen-compatible tamoxifen aziridine labeling. Hence these two residues,
      although far apart in the primary linear sequence of the ER protein, must be
      close in the three-dimensional structure of the protein, in the ER ligand binding
      pocket, so that the ligand can reach either site. Site-directed and region
      specific chemical mutagenesis have identified a region around C530 important in
      discrimination between estrogens and antiestrogens, and other mutants have
      allowed identification of residues important in hormone-dependent transcriptional
      activation. Some transcriptionally inactive ER mutants also function as potent
      dominant negative ERs, suppressing the activity of wild-type ERs at low
      concentrations. These studies are beginning to provide a more detailed picture of
      the ER hormone binding domain and amino acids important in ligand binding and
      discrimination between different categories of agonist and antagonist ligands.
      Such information will be important in the design of maximally effective
      antiestrogens. In addition, since there is now substantial evidence for a mixture
      of wild-type and variant ERs in breast cancers, our studies should provide
      insight about the bioactivities of these variant receptors and their roles in
      modulating the activity of wild type ER, and should lead to a better
      understanding of the possible role of variant receptors in altered response or
      resistance to antiestrogen and endocrine therapy in breast cancer.

PMID- 8260728
TI  - William L. McGuire Memorial Symposium. Estrogen and progestin effects in human
      breast carcinogenesis.
AB  - The influences of estrogen and progestin on human mammary neoplasia are reviewed
      with a view to identifying what is known about their effects. Estrogens promote
      growth of established cancer and pharmacological levels of progestins induce
      remission. In vivo, highest proliferation of histologically normal mammary
      epithelium occurs in the progestogenic phase of the menstrual cycle or under the
      progestogenic influence of oral contraceptives. Little additional hard data exist
      to indicate whether progestins promote or inhibit human mammary carcinogenesis.
      Effects on proliferation, steroid receptor content and development are discussed
      together with interpretation of epidemiological data on risk factors that have
      hormonal components. Progestins may not be the benign or beneficial agents
      previously supposed, and there are virtually no data to suggest that they are
      antiestrogenic. It is hypothesized that carcinogenesis may be accompanied by
      increased sensitivity to estrogen, which provides a growth advantage to the tumor
      by maximizing use of the low estrogen concentrations encountered in the
      postmenopausal state.

PMID- 8260729
TI  - Modulators of cellular protein phosphorylation alter the trans-activation
      function of human progesterone receptor and the biological activity of
      progesterone antagonists.
AB  - Addition of progesterone to breast cancer cells in vivo increases phosphorylation
      of human progesterone receptor (PR), suggesting that phosphorylation has a
      regulatory role in producing the activated form of receptor. Kinetic analysis
      indicates that hormone-dependent phosphorylation is sequential and that early
      stages of phosphorylation(s) are closely associated with enhancement of PR-DNA
      binding while later stages are associated with a trans-activation function.
      Various agents that stimulate cellular protein phosphorylation (8-Br cAMP,
      okadaic acid, TPA) functionally synergize with progesterone to enhance
      progesterone-dependent PR trans-activation in intact cells. These results suggest
      that protein phosphorylation does have a role in modulating the trans-activation
      function of PR in vivo. They also demonstrate cross-talk between second messenger
      signal transduction pathways and nuclear steroid receptors. Whether the
      phosphorylated target that provides the link between these two signal
      transduction pathways is PR itself or another protein involved in PR-mediated
      gene transcription is not known. Positive cooperative interactions were also
      observed between cAMP signaling pathways and the progesterone antagonist RU486,
      that resulted in RU486 exerting substantial agonist activities. This ability of
      cross-talk between second messenger and steroid receptor signal transduction
      pathways to override the antagonistic effects of RU486 suggests a novel mechanism
      to explain the problem of resistance to clinically important steroid antagonists.

PMID- 8260730
TI  - William L. McGuire Memorial Symposium. Control of breast cancer cell growth by
      steroids and growth factors: interactions and mechanisms.
AB  - Over the past two decades, the simple model for control of breast cancer growth
      involving one or two factors acting directly or indirectly via endocrine pathways
      has turned into a complex model implicating numerous interacting factors and the
      diverse cell populations constituting breast tumors. Current approaches to breast
      cancer therapy now require integration of these multiple parameters and enhanced
      understanding of the different levels of their intricate interactions.

PMID- 8260731
TI  - William L. McGuire Memorial Symposium. 1,25(OH)2D3 modulation of mammary tumor
      cell growth in vitro and in vivo.
AB  - The biological role of 1,25(OH)2D3 in controlling Ca++ homeostasis in the body
      has been identified and widely investigated for a long time. More recently its
      effect in regulating cell proliferation or differentiated activity was described
      in a variety of normal and malignant cells. The present study was carried out to
      investigate the different aspects and biological mechanisms of this activity and
      to determine if the use of 1,25(OH)2D3 in the treatment of breast cancer patients
      could be considered. It is found that 1,25(OH)2D3 reduces the proliferation of
      MCF-7 and BT-20 cells lines regardless of their sex steroid receptor status. This
      effect is related to the concentration, from 10(-12) M to 10(-8) M. Its amplitude
      is less in other cell lines, but it opposes the EGF-induced increase of
      proliferation. It is observed that the proliferation rate of MCF-7 and BT-20
      cells is increased when these tumor cells are cocultured with fibroblasts derived
      from breast tumor biopsies and that 1,25(OH)2D3 reverses this process. Moreover,
      experiments on DMBA induced mammary tumors in Sprague Dawley rats found that
      1,25(OH)2D3 given at non toxic doses reduces significantly the tumor
      proliferation. These data showed that 1,25(OH)2D3 at low doses is effective on
      the proliferation of BT-20 and MCF-7 cells and on the paracrine growth
      stimulatory effect observed in the presence of fibroblasts. They suggest that
      1,25(OH)2D3 or related synthetic molecules which are less active on Ca++
      metabolism could be useful in the treatment of breast cancer patients.

PMID- 8260732
TI  - William L. McGuire Memorial Symposium. The role and prognostic significance of
      p53 gene alterations in breast cancer.
AB  - Alterations in the p53 tumor suppressor gene are the most frequent genetic
      changes found in breast cancer, with an incidence reported in a range of 15 to
      50%. The incidence of p53 alterations is approximately 15% for in situ carcinoma,
      while for invasive node-positive disease it is 2 to 3 times higher. This high
      rate of alteration suggests that the gene plays a central role in the development
      of breast cancer. The p53 gene functions as a negative regulator of cell growth.
      Alterations in the gene lead to loss of its usual negative growth regulation and
      more rapid cell proliferation. Since p53 alteration can reflect a more advanced
      state of progression and a higher rate of proliferation, breast tumors that have
      a p53 alteration could have a greater probability of having micrometastasis. p53
      alterations could therefore be a prognostic factor for recurrence after primary
      local therapy. Consistent with this hypothesis, several independent studies using
      different methodologies have found that breast tumors with altered p53 have a
      worse prognosis and are also more likely to have other poor prognostic factors.

PMID- 8260733
TI  - Pathophysiology of reflux oesophagitis and peptic ulcer.
AB  - The pathophysiological mechanisms of peptic ulcer and reflux oesophagitis are
      described. Special attention has been paid to the gastric mucosal defence
      factors, e.g. epidermal growth factor, mucosal blood flow and gastric mucus. The
      possible effects of neutrophils activation on nitric oxide generation and gastric
      mucosal capillary blood flow are discussed. Most useful diagnostic tests of
      gastro-oesophageal reflux are presented. The role of antacids in the treatment of
      reflux oesophagitis and reflux without oesophagitis is underlined.

PMID- 8260734
TI  - Non-ulcer dyspepsia and gastritis--clinical aspects.
AB  - Although patients with non-ulcer dyspepsia (NUD) and peptic ulcer disease present
      similar symptoms, the two diseases are pathophysiologically completely different
      and should be treated accordingly. The diagnosis of NUD is still based on
      negative criteria, i.e., organic diseases must be excluded. The majority of the
      patients with NUD have a functional disorder possibly as a consequence of
      psychological stress which, by activating processes within the central nervous
      system, may evoke a sequence of reactions; By suppressing the vagal tone, fundic
      adaptation to ingested food may be impaired and the gastric antrum abnormally
      filled. The latter may contribute to largely unrecognized cause of epigastric
      discomfort. Increased responsiveness or hypersensitivity to visceral (gastric
      distention) and psychological (mental stress) stimuli may constitute important
      factors contributing to perception of discomfort, possibly as abnormal perception
      of normal events. The treatment of such a complex condition is difficult and may
      not be solved by medical intervention solely. Patients presenting with dyspepsia
      of unknown origin, should primarily be treated with antacids. Treatment with
      prokinetics (cisapride) is rational and worth trying. Antacids and H2-receptor
      antagonists may help in NUD patients with acid reflux. In patients with
      Helicobacter pylori-induced gastritis Al-Mg-antacids suppress, but alone do not
      eradicate the bacteria. Antacids in combination with oxytetracycline and
      metronidazole eradicate H. pylori in about one half of the infected patients.

PMID- 8260735
TI  - New aspects of clinical pharmacology of antacids.
AB  - Most antacids contain magnesium and/or aluminium hydroxide but some include also
      bicarbonate and calcium carbonate. The net effect of antacid action is the
      reduction in gastric acidity and in peptic activity but recent studies indicate
      that aluminium-containing antacids exhibit the cytoprotective activity or
      enhancement of natural mucosal defense mechanisms. This protective action has
      been attributed, in part, to the release of endogenous prostaglandins but other
      mediators such as hexa-aquo-aluminium cation and nitric oxide have also been
      proposed. Aluminium-containing antacids are known to accelerate the healing of
      chronic gastroduodenal ulcerations and this has been attributed primarily to
      their acid neutralizing capacity. Since antacids interact with luminal epidermal
      growth factor (EGF) which exhibits ulcer healing properties it has been proposed
      that this peptide is implicated in the healing of gastroduodenal ulcerations by
      these drugs.

PMID- 8260736
TI  - Clinical use of antacids.
AB  - Antacids have for long been regarded as the mainstay of pharmacologic therapy in
      patients with dyspepsia. The advent of the histamine H2-antagonist and of proton
      pump inhibitors has provided simpler and overall more efficient therapeutic
      modalities for severe forms of dyspepsia. This relates especially to aggressive
      forms of peptic ulcer disease and severe reflux oesophagitis, where even high
      dose histamine H2-antagonist therapy has its clear limitations. Antacids
      nevertheless continue to be widely used in less severe forms of dyspepsia,
      especially in patients suffering from heartburn. In such patients self medication
      of antacids as first therapeutic measure is still very common. This is well
      exemplified by an American nd British survey. Out of 6760 randomly selected
      British general practice patients 875 suffered from reflux-like symptomatology
      without having consulted their physician for the symptomatology for minimum one
      year. Antacids were taken by 61% of them. The advent of controlled endoscopic
      trials and the emergence of the H2-receptor blockers as a yardstick of ulcer
      therapy, however, facilitated reappraisal of the value of antacids in various
      conditions. This has given a clear-cut answer in well defined entities such as
      peptic ulcer disease and stress ulcer prophylaxis but has left many open
      questions in heterogeneous conditions especially in and around gastroesophageal
      reflux disease.

PMID- 8260737
TI  - Tolerance of antacids.
AB  - The use of aluminium containing antacids raises the question of toxicity. Uptake
      of excessive quantities of aluminium may produce neurological symptoms and
      osteomalacia. Provided that renal function is intact ingested aluminium from
      antacids is absorbed to a small extent from the gastrointestinal tract resulting
      in a transient increase in plasma aluminium levels which never reach toxic
      concentration, and therefore can be regarded as safe.

PMID- 8260738
TI  - [A review of epidemiological studies on the relationship of residential
      electromagnetic exposure to cancer].
AB  - Since 1979 epidemiological studies have been published that suggest that
      residential exposure to electromagnetic fields generated mainly near power lines
      could increase the risk of childhood cancer such as leukemia and neurological
      tissue tumor. However, methodological shortcomings of the studies are such that
      the evidence is not strong enough to allow conclusions to be drawn. Similar
      studies have also been published for adults. Except for cases of occupational
      exposure the findings do not show that residential electromagnetic field exposure
      is a risk factor. However, information is too sparse to permit firm conclusions.
      The existing literature strongly indicate further researchers in the area should
      be pursued.

PMID- 8260739
TI  - [Prediction of future trends of HIV infection and AIDS in Japan].
AB  - Current status and future trends of HIV infection and AIDS in Japan were
      estimated based on AIDS surveillance data up until 1992, excluding HIV infection
      from blood products and blood-borne transmission. The coverage rate of reports of
      HIV infection was estimated as the proportion of the reported AIDS cases who are
      also included in reports of HIV infection. Current numbers of HIV infected
      persons were then estimated to be the reported numbers divided by the coverage
      rate. Future numbers of HIV infected persons were predicted by extrapolation.
      Future numbers of AIDS cases were predicted based on the predicted numbers of HIV
      infected persons and the incubation distribution. The results were as follows: 1)
      The coverage rate of the reports of HIV infection was estimated to be 11.5%. 2)
      The numbers of HIV infected persons were estimated to be 2,900 in Japanese and
      4,500 in foreigners by the end of 1992, and are predicted to be 7,700 in Japanese
      and 15,500 in foreigners by the end of 1997. 3) The numbers of AIDS cases were
      reported to be 125 in Japanese and 52 in foreigners by the end of 1992, and are
      predicted to be 1,100 in Japanese and 1,600 in foreigners (including AIDS cases
      developed after return to home country) by the end of 1997.

PMID- 8260740
TI  - [Social and health conditions in a former coal mining area in Fukuoka, Japan].
AB  - The purpose of this study was to evaluate the residual effect of the former coal
      mining industry upon the social and health conditions of an area that was the
      side of a once prospering coal mining industry. The area was partitioned into two
      types of districts according to the percentage of residential housing that was
      for coal miners. The first district consisted predominantly of tenant homes for
      the coal miners (coal miner district) and the remaining area made up the second
      district (other district). Health conditions in the two districts were compared
      by standard mortality rates (SMR), and age-specific death rates for all disease
      and non-disease related deaths. Social conditions were compared based upon sex,
      age, employment stauts, and job type. The results were as follows: (1) Total
      unemployment rate, the percentage of households with no income earner, and single
      family households, was higher in the coal miner district than in the other
      district. (2) The SMRs for all deaths in the coal miner district were
      significantly higher than in the other district. (3) While not significant the
      SMRs for disease related deaths were higher in the coal miner district. (4) Even
      in the younger age group (both male and female), while having no direct
      relationship with the coal mining industry, the SMRs were higher in the coal mine
      district. (5) The SMRs for suicides and homicides that occurred among the men
      residing in the coal miner district were higher. In conclusion, the social and
      health conditions in this former coal mining residential area were poorer than in
      the other area.

PMID- 8260741
TI  - [A report on the effect of sheltered workshop activities on the social living
      activity of the mentally ill--analysis of research on workshop clients].
AB  - The effect of sheltered workshop activities on the social living activity of the
      mentally ill was studied in order to evaluate the role and level of function of
      workshop activities as a self support and employment system for clients, and to
      determine the future tasks of the workshop and rehabilitative services in the
      community. The following results were observed: 1) Clients' social living ability
      appears to be poor, especially in questions related to personal relationships and
      time distribution, where less than 50% of the clients answered "Possible without
      assistance". This appears to be characteristics of the living behaviors of
      mentally ill individuals. 2) Most of the families of the clients evaluated the
      sheltered workshop activities positively in terms of increasing the clients'
      social living ability. 3) A survey of families showed that by utilizing the
      workshop much progress has been made toward improving those living behaviors
      which are easily made into habits and lifestyle pattern. On the other hand,
      personal relationships and living behaviors which require coping flexibility, are
      much more refactory. Based on those results, the future task of sheltered
      workshops and the supportive role of the public health center need to be examined
      further.

PMID- 8260742
TI  - [Early detection of obesity in male adults using a combination of body index and
      bioelectrical impedance method].
AB  - Obesity is an excess of body fat frequently resulting in a significant impairment
      of health. Body index derived from body weight and height is widely available in
      Japan. However, body index cannot express the fat deposition in the body.
      Screening for early obesity was studied using a combination of body index and
      bioelectrical impedance for detecting fat deposition. Three hundred twenty-nine
      male subjects with normal body index participated in this study. Blood pressure,
      uric acid, total cholesterol, high density lipoprotein cholesterol, triglyceride,
      GOT, GPT, gamma-GTP, choline esterase and glucose tolerance after a 75-gram
      glucose load were measured. The following results were obtained. 1. Among 321
      subjects with normal body index, 95 subjects had body fat exceeding 23% as
      measured by bioelectrical impedance. 2. By matched-pair comparison in the
      subjects whose body mass indices were within +/- 10% fasting plasma glucose,
      triglyceride, GOT, GPT, gamma-GTP and choline esterase were significantly higher
      and high density lipoprotein cholesterol was significantly lower in subjects with
      fat deposition over 23% than in the 92 matched controls with body fat less than
      23%. In conclusion, bioelectrical impedance appears to be useful for detecting
      early stages of obesity in subjects with normal body index.

PMID- 8260743
TI  - [Correlates of cigarette smoking among junior and senior high school students in
      Japan].
AB  - Data from a nationwide cross-sectional survey of the smoking status among junior
      and senior high school students in Japan conducted in 1990, were utilized to
      provide sociodemographic correlates of the use of cigarettes. The study was based
      on data from 57, 189 students. The analyses examined the relationship between
      smoking status and 9 explanatory variables, using multiple logistic regression
      for both males and females. The results of logistic regression analyses revealed
      the following main effects: 1) Smoking by a friend had the strongest relationship
      to smoking status of students for both sexes. The relative risks for having a
      smoking experience if a friend smoked were 3.45 for junior high school boys, 5.24
      for junior high school girls, 3.65 for senior high school boys and 5.54 for
      senior high school girls and the risks for current smoking if a friend smoked
      were 8.54, 15.28, 6.99 and 12.47, respectively. 2) Among both boys and girls,
      smoking experience and current smoking was significantly more likely if a brother
      or sister, or mother smoked. Awareness of the harm of smoking was also an
      important correlate in both sexes. Whether the students enjoyed their school life
      was significantly related to current smoking status for females, but not for
      males. 3) The relative risks for current smoking if their mothers smoked were
      1.60 for junior high school boys, 1.78 for junior high school girls, 1.61 for
      senior high school boys and 1.61 for senior high school girls. Fathers' smoking
      was not selected in this stepwise multiple logistic regression model. Therefore,
      mothers' smoking appears to be a stronger correlate of smoking status among
      students than fathers' smoking. 4) The relative risks for smoking experience and
      current smoking if there were smokers in the family, were higher among junior
      high school students than senior high school students.

PMID- 8260744
TI  - [Association of borderline glucose tolerance to dietary intakes and life style
      cross sectional study of urban male workers examined at the annual health
      examination].
AB  - In this study, the association of borderline glucose tolerance to dietary intakes
      and life style was examined. Subjects were 2215 male workers aged 23 through 69,
      who visited a medical examination center in Tokyo between January 1987 through
      February 1989 for an annual health examination. Based on results of a 75 gram
      glucose tolerance test, subject were divided into three groups: 1. diabetes
      mellitus,2. borderline glucose tolerance, and 3.normal. Nearly one half of the
      subjects were found to have borderline glucose tolerance. Clinical results and
      ages of the borderline glucose tolerance group were between those of the normal
      and the diabetes mellitus groups. Differences between the borderline glucose
      tolerance group and the normal group with respect to dietary intake and life
      style were analyzed by a logistic model. Because associations were found to
      differ by obesity level (calculated by Katsura method) in the primary analysis,
      second stage analysis was performed with obesity level. For subjects who were
      less than 10% overweight, borderline glucose tolerance was more frequent with the
      following characteristics: age over 40; administrative or sales position; eating
      and drinking after 9:00 pm; consumption of more than three caps of coffee with
      sugar per day; having a sweet taste; eating rapidly; positive for Type A
      personality score. For the subjects who were more than 10% overweight, borderline
      glucose tolerance was more frequent with the following: age less than 40;
      consumption of more than three caps of coffee with sugar per day; preferring
      fatty foods; and positive for Type A personality score. These results indicate
      the importance of dietary education especially in workers who are less than 10%
      overweight.

PMID- 8260745
TI  - [Smoking restrictions in medical schools in Japan].
AB  - The theme of the 6th WHO World Non-Smoking Day in 1993 was "Health services: our
      window to a tobacco-free world". A survey of the public health departments of all
      medical schools and universities was conducted in April, 1992 in order to
      investigate the state of smoking restrictions in those departments responsible
      for training in health services. Responses were received from 76 schools out of
      80. The results were as follows: 1) In school cafeteria: Smoking prohibited
      (17.8%), Separate smoking/non-smoking areas (21.9%), Unrestricted smoking
      (60.3%), In student lounges: Smoking prohibited (2.9%), Separate Smoking/non
      smoking areas (7.1%), Unrestricted smoking (90.0%), 2) The number of schools with
      tobacco vending machines: 59 schools (77.6%), 3) In medical faculty meetings:
      Smoking prohibited--32 schools (42.1%), Unrestricted smoking--22 schools (28.9%),
      No rules but no smokers--22 schools (28.9%), A total of 54 schools (71.0%) have
      established non-smoking meetings. 4) The number of school that give no attention
      to raking students aware of smoking risks: 6 schools As a result of this
      investigation, one national and one private medical school initiated prohibition
      of smoking at medical faculty meetings. In order to stimulate consciousness of
      the health hazards of smoking in future medical professionals, freshmen
      orientation should be utilized for teaching about the risks of both tobacco and
      "chug-a-lugging" of alcoholic beverages. In addition, the elimination of tobacco
      vending machines from all medical department area is strongly indicated.

PMID- 8260746
TI  - [Trend of visiting medical facilities in member of the national health insurance
      in a rural town].

PMID- 8260747
TI  - Gene-specific damage produced by cisplatin, ormaplatin and UV light in human
      cells as assayed by the polymerase chain reaction.
AB  - The level of DNA damage in the total genome of leukocytes from patients receiving
      cisplatin therapy has been previously correlated with therapeutic outcome. Based
      on the fact that unrepaired damage in transcribed genes has been well correlated
      with sensitivity to a number of DNA damaging agents, the correlations with
      therapeutic response might be improved if the level of DNA damage in specific
      genes was assessed. We previously established a polymerase chain reaction (PCR)
      based assay to measure cisplatin lesions in specific genes. The major advantages
      of this assay include its potential to quantify DNA lesions produced by any DNA
      damaging agent, and to measure it in minute samples of cells. This assay has been
      further improved to realize this potential. Specifically, cells were damaged with
      cisplatin, a related analogue ormaplatin, and ultraviolet light, and PCR was
      performed on the DNA from 1000 cells after direct lysis with no purification.
      Human HL-60 cells were used to compare the efficacy of the various agents to
      damage the alpha-fetoprotein gene. This was then extrapolated to damage in the
      total genome and compared to the cytotoxicity for each agent. At a dose that
      killed 50% of the cells, ormaplatin, cisplatin and ultraviolet light produced
      19,200, 48,000, and 1,080,000 lesions per cell, demonstrating that ormaplatin
      lesions were the most effective at killing cells. Mononuclear cells were obtained
      from freshly isolated blood from five individuals. These cells were damaged with
      the three agents, and PCR of the alpha-fetoprotein gene was performed. No
      significant difference between the individuals was observed in the level of DNA
      damage produced by any of the agents.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260748
TI  - 31P and 13C NMR spectroscopic study of wild type and multidrug resistant Ehrlich
      ascites tumor cells.
AB  - Steady-state 31P NMR spectra of wild type EHR2 Ehrlich ascites tumor cells and
      multidrug resistant EHR2/DNR+ cells, immobilized in agarose threads, and
      continuously perfused with medium, showed temperature-dependent differences in
      the levels of intracellular phosphate metabolites. At 37 degrees C, the EHR2/DNR+
      cells contained four times more phosphocreatine (PCr) than the EHR2 cells. At 20
      degrees C, the EHR2 cells contained 80% more of phosphodiesters (PDE), the levels
      of PCr being equal. The quantitative metabolite level data are based on T1
      relaxation times data and are normalized for the protein content of the cells.
      Perfusion of the cells with azide, an inhibitor of mitochondrial respiration, had
      no effect on the ATP level, and caused no changes in glucose consumption and
      lactate production. Azide perfusion, combined with glucose depletion, caused
      rapid drop in the ATP content, which was reestablished after renewed perfusion
      with glucose. Similarly, perfusion with 2,4-dinitrophenol, an uncoupler of the
      respiration chain, had no effect on the phosphate metabolites. These results
      demonstrate that aerobic glycolysis is the main route by which glucose is
      metabolised under the conditions used (glucose concentration in medium 2 g/L).
      Rates of uptake and phosphorylation of 2-deoxy-D-glucose were measured by
      following the formation of intracellular [6-13C]2-deoxy-D-glucose-6-phosphate by
      13C NMR; at 37 degrees C the observed rates for EHR2 and EHR2/DNR+ cells were
      equal, about 10 nmol/(min x mg protein), whereas at 20 degrees C the wild type
      cells produced the 6-phosphate at an approximately twice the rate found for the
      resistant cells [about 4 and 2 nmol/(min x mg protein), respectively].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8260749
TI  - Decreased expression of manganese superoxide dismutase mRNA and protein after
      immortalization and transformation of mouse liver cells.
AB  - Altered levels of superoxide dismutase (SOD), the enzyme that scavenges toxic
      superoxide anion produced during normal metabolism or after oxidative insult,
      have been implicated in multistage carcinogenesis of both rodents and humans.
      Using a mouse liver cell model, we report here that after cellular
      immortalization, both copper- and zinc-containing superoxide dismutase (Cu,ZnSOD)
      and manganese superoxide dismutase (MnSOD) activities decreased dramatically and
      that cellular transformation further decreased MnSOD but not Cu,ZnSOD activity.
      Decreased enzyme activities seen in transformed cells (Tx) were due to decreased
      amounts of immunoreactive enzyme protein that results from decreased superoxide
      dismutase mRNA expression. This downregulation of gene expression may occur at
      the transcriptional level, as suggested by results with cycloheximide (Chx) and
      actinomycin D (AcD) treatments.

PMID- 8260750
TI  - A comparison of the effects of aphidicolin and other inhibitors on topoisomerase
      II-directed cytotoxic drugs.
AB  - We have compared the effects of a number of inhibitors including aphidicolin, 2,4
      dinitrophenol (DNP) and novobiocin on the in vitro cytotoxicity of several
      topoisomerase II (topo II)-directed agents, using cultured murine Lewis lung
      carcinoma cells. These agents comprised amsacrine, CI-921 (9-[(2-methoxy-4
      methylsulfonylamino)phenylamino]-N,5-dimethyl-4- acridinecarboxamide isethionate,
      isethionate, a derivative of amsacrine), DACA (N-[2-(dimethylamino)ethyl]acridine
      4-carboxamide dihydrochloride, a new DNA intercalator with high solid tumor
      activity), daunorubicin, doxorubicin, epirubicin, etoposide, mitoxantrone, and
      teniposide. Novobiocin, an antibiotic that affects topo II action, reduced the
      cytotoxic effect of DACA as well as that of amsacrine and doxorubicin, and
      reduced the extent of G2-phase arrest by DACA. DNP, an uncoupler of mitochondrial
      respiration, inhibited drug action in a manner similar to that of novobiocin but
      to a smaller extent. Aphidicolin, a specific inhibitor of DNA polymerase-alpha,
      reduced the cytotoxic effect of amsacrine, CI-921, etoposide, and teniposide but
      not that of DACA, daunorubicin, doxorubicin, epirubicin, or mitoxantrone. The
      immediate effect of each topo II-directed agent on the incorporation of thymidine
      into DNA was also measured at a drug concentration (D10) that killed 90% of
      cells. Susceptibility to aphidicolin reversal was strongly correlated with
      inhibition of thymidine incorporation (r = 0.91; p < or = 0.001). The results
      suggest that the involvement of DNA replication in the cytotoxic action of topo
      II-directed agents differs according to the agent used.

PMID- 8260751
TI  - Effect of Bcl-2 on ionizing radiation and 1-beta-D-arabinofuranosylcytosine
      induced internucleosomal DNA fragmentation and cell survival in human myeloid
      leukemia cells.
AB  - 1-beta-D-Arabinofuranosylcytosine (ara-C) is an anti-leukemic agent that
      incorporates into cellular DNA leading to inhibition of DNA synthesis and loss of
      clonogenic survival. In contrast, ionizing radiation induces DNA damage through
      the generation of reactive oxygen intermediates. Although little is known of the
      specific determinants of ara-C and ionizing radiation-induced cytotoxicity,
      recent work has shown that both are capable of inducing internucleosomal DNA
      fragmentation in a pattern consistent with programmed cell death (apoptosis). In
      order to assess the importance of apoptosis in drug and ionizing radiation
      induced cytotoxicity in the U-937 myelomonocytic cell line, we created cell lines
      that constitutively express a transfected bcl-2 gene. Bcl-2 was capable of
      inhibiting 40-50% of the ara-C and ionizing radiation-induced internucleosomal
      DNA fragmentation at all tested concentrations. However, cell survival following
      exposure to these agents was only increased in the bcl-2 transfectants at
      relatively low doses of ara-C and ionizing radiation. These data demonstrate that
      although bcl-2 is capable of inhibiting ara-C and ionizing radiation-induced DNA
      fragmentation in myeloid cells, it increases cell survival only at low doses of
      these agents. This suggests that apoptosis may be a less important mechanism of
      cytotoxicity at higher doses of ara-C and ionizing radiation than it is at lower
      doses.

PMID- 8260752
TI  - Reference listings in cancer research.

PMID- 8260754
TI  - British Journal of Theatre Nursing Readership Survey 1992.

PMID- 8260753
TI  - Assessing patients' fears.

PMID- 8260755
TI  - Work experience.

PMID- 8260756
TI  - Contact dermatitis.

PMID- 8260757
TI  - Theatre footwear: a health hazard?
AB  - Theatre footwear frequently appears to be contaminated with blood. We assessed
      objectively the nature and degree of contamination of theatre shoes after
      cleaning. Two hundred pairs of theatre shoes were randomly selected from three
      hospitals in South East Wales. Hospital 1 (H1), 100 pairs of shoes, Hospital 2
      (H2), 40, Hospital 3 (H3), 60. They were examined for general appearance, the
      presence of bacterial pathogens and blood, using a leuchomalachite green assay.
      The majority of shoes were dirty, 63% in H1, 80% in H2, and 95% in H3. Six per
      cent of shoes in H1, 2.5% in H2 and 0% in H3 were contaminated with
      staphylococcus aureus. No shoes were contaminated with pseudomonas aeruginosa.
      Thirty six per cent of shoes in H1, 40% in H2 and 57% in H3 were contaminated
      with blood. In H1 it was possible to determine the grade of staff to whom the
      shoes belonged. Fifty eight per cent of consultant surgeons' shoes tested
      positive for blood, 50% of junior surgeons, 16% of operating department
      assistants and none of nurses' theatre shoes. The high level of blood
      contamination following cleaning may pose a potential HIV or hepatitis B risk to
      patients, manual shoe cleaner and surgeons. We have demonstrated that current
      shoe cleaning practices are ineffective. We propose methods that should eliminate
      this risk. Procedures will need to be defined.

PMID- 8260758
TI  - Smoothed nonparametric back-projection of AIDS incidence data with adjustment for
      therapy.
AB  - Back-projection is a major tool for assessing the extent of the HIV epidemic. Its
      application relies on a model for the incubation period of AIDS into which the
      administration and effect of therapy has been incorporated. We propose a
      compartmental model with proportional transition rates to describe variation and
      changes in the duration of the incubation period. The model is easily related to
      available data and offers fast computation. Its detailed and direct reflection of
      the administration and effect of therapy makes it relatively easy to ensure that
      therapy has been accommodated to an appropriate extent. The effect of therapy on
      back-projection estimates of the HIV epidemic curve is demonstrated with an
      application to Australian AIDS incidence data.

PMID- 8260759
TI  - Does migration stabilize local population dynamics? Analysis of a discrete
      metapopulation model.
AB  - A discrete model for a metapopulation consisting of two local populations
      connected by migration is described and analyzed. It is assumed that the local
      populations grow according to the logistic law, that both populations have the
      same emigration rate, and that migrants choose their new habitat patch at random.
      Mathematically this leads to a coupled system of two logistic equations. A
      complete characterization of fixed point and two-periodic orbits is given, and a
      bifurcation analysis is performed. The region in the parameter plane where the
      diagonal is a global attractor is determined. In the symmetric case, where both
      populations have the same growth rate, the analysis is rigorous with complete
      proofs. In the nonsymmetric case, where the populations grow at different rates,
      the results are obtained numerically. The results are interpreted biologically.
      Particular attention is given to the sense in which migration has a stabilizing
      and synchronizing effect on local dynamics.

PMID- 8260760
TI  - Theory of the locomotion of nematodes: control of the somatic motor neurons by
      interneurons.
AB  - The only animal of which the complete neural circuitry is known at the
      submicroscopical level is the nematode Caenorhabditis elegans. This anatomical
      knowledge is complemented by functional insight from electrophysiological
      experiments in the related nematode Ascaris lumbricoides, which show that Ascaris
      motor neurons transmit signals electrotonically and not with unattenuated spikes.
      We developed a mathematical model for electrotonic neural networks and applied it
      to the motor nervous system of nematodes. This enabled us to reproduce
      experimental results in Ascaris quantitatively. In particular, our computed
      result of the velocity v approximately equal to 6 cm/s of neural excitations in
      the Ascaris interneurons supports the simple hypothesis that the so-called
      rapidly moving muscular wave is produced by a neural excitation traveling at the
      same speed in the interneuron as the muscular wave. In C. elegans, the computed
      velocity v approximately equal to 8-30 cm/s of signals in the interneurons is
      much larger than the observed velocity v approximately equal to 0.2 cm/s of the
      body wave. Therefore, the hypothesis that the muscular wave is produced by a
      synchronous neural excitation wave cannot hold for C. elegans. We argue that
      stretch receptor control is the most likely mechanism for the generation of body
      waves used in the locomotion of C. elegans. Extending the simulation to larger
      groups of neurons, we found that the neural system of C. elegans can operate
      purely electrotonically. We demonstrate that the same conclusion cannot be drawn
      for the nervous system of Ascaris, because in the long (l approximately equal to
      30 cm) interneurons the electrotonic signals would be too strongly attenuated.
      This conclusion is not in contradiction with the experimental findings of
      electrotonic signal propagation in the motor neurons of Ascaris because the
      latter are shorter (l approximately equal to 5 cm) than the interneurons.

PMID- 8260761
TI  - Cocontraction of pairs of antagonistic muscles: analytical solution for planar
      static nonlinear optimization approaches.
AB  - It has been stated in the literature that static, nonlinear optimization
      approaches cannot predict coactivation of pairs of antagonistic muscles; however,
      numerical solutions of such approaches have predicted coactivation of pairs of
      one-joint and multijoint antagonists. Analytical support for either finding is
      not available in the literature for systems containing more than one degree of
      freedom. The purpose of this study was to investigate analytically the
      possibility of cocontraction of pairs of antagonistic muscles using a static
      nonlinear optimization approach for a multidegree-of-freedom, two-dimensional
      system. Analytical solutions were found using the Karush-Kuhn-Tucker conditions,
      which were necessary and sufficient for optimality in this problem. The results
      show that cocontraction of pairs of one-joint antagonistic muscles is not
      possible, whereas cocontraction of pairs of multijoint antagonists is. These
      findings suggest that cocontraction of pairs of antagonistic muscles may be an
      "efficient" way to accomplish many movement tasks.

PMID- 8260763
TI  - AHNA certificate program in holistic nursing courses.

PMID- 8260762
TI  - A model of phagosome motion within cells based on cytomagnetometric measurements.
AB  - Cytomagnetometry is the study of the intracellular movement and rheological
      properties of living cells by magnetic measurement. This paper summarizes the
      mathematics involved in the measurement and proposes a new model of phagosome
      motion in which a motor protein such as myosin and a protein filament such as
      microfilament play the role of the actomyosin system in the muscle. The
      rotational random walk is assumed to result from interactions of these proteins.
      The model makes predictions about the results of the experiments employing
      magnetic particles introduced into the cells by phagocytosis. The predictions are
      qualitatively consistent with the results of recent preliminary experiments.

PMID- 8260764
TI  - The power of a healing network: we did it!

PMID- 8260765
TI  - The garden of healing fragrances.

PMID- 8260766
TI  - Environmental public health: issues for the new millennium.

PMID- 8260767
TI  - 'Maternal-infant health beliefs and infant feeding practices: the perception and
      experience of Vietnamese women in Sydney'.

PMID- 8260768
TI  - The proposed 'Consent to Medical Treatment and Palliative Care Act'.

PMID- 8260769
TI  - First-line nurse managers in NSW: perceived role competencies (Part I).
AB  - A survey of 412 first-line nurse managers employed in hospitals in New South
      Wales, Australia was undertaken to determine the competencies they believed an
      individual should possess to fulfil that managerial role. Factor analyses
      identified both the significant functions of the role as well as areas of role
      conflict and confusion. Thirteen factors identified from four major scales
      indicated that first-line nurse managers perceived their role to be extremely
      comprehensive in terms of managerial knowledge and skills. The analyses clearly
      indicate that competencies related to staffing and financial issues are perceived
      to be essential to role performance. However, the correlation coefficients
      (factor loadings) indicate that ambiguity exists with competencies concerning
      patient care, perhaps as the remnants of the charge nurse role are discarded.

PMID- 8260770
TI  - Holism, care and nursing: points of reflection during the evolution of a
      philosophy of nursing statement.
AB  - An exploration of the diversity and complexity of perspectives from which holism
      and care can legitimately be constructed. The preparation of a document for
      accreditation of a proposed pre-registration Bachelor of Nursing award was the
      impetus for this exploration. School members deemed holism and care to be central
      to our philosophy of nursing statement, however, difficulty arose in determining
      a shared understanding of these notions. Through reflective deliberation and a
      review of the literature, the authors attempted to unravel the range of meanings
      given to these problematic terms.

PMID- 8260771
TI  - Primary health care: a clarification of the concept and the nursing role.
AB  - Various authors have noted that the terminology relating to 'community nursing',
      'community health nursing' and 'public health nursing' have continued to change
      over the years, and that this has lead to a lack of conceptual clarity (Flynn
      1988, Highrighter 1984, Sills & Goeppinger 1985). With the addition of the
      concept of primary health care (WHO-UNICEF 1978) there has been added confusion
      about the meaning of terminology used. This confusion contributes to uncertainty
      about nurses' practice role in primary health care. This paper explores the
      differing approaches to interpreting the meaning of primary health care and
      addresses itself to clarifying the community health nursing practice role in
      primary health care.

PMID- 8260772
TI  - Looking back by listening: reflections on an oral history.
AB  - Oral history values the life experience of others. It provides insight into past
      events, offering a colourful historical perspective which is alive with emotion
      and rich in character. This account presents recollections of health care
      training from a markedly different social, economic, cultural and political
      environment. Reflecting on the oral history allows exploration of aspects of the
      interview. Confidentiality, respect, familiarity, bias, language and the
      generation gap impacted on the process. The potential of older members of the
      community to contribute to the compilation of historical accounts is recognised
      and their active role valued.

PMID- 8260773
TI  - Cultural differences.

PMID- 8260774
TI  - Whose choice?

PMID- 8260775
TI  - There is more to CPR than ABC.

PMID- 8260777
TI  - Why care about informed consent?

PMID- 8260776
TI  - Challenging contrasts: scientists and nurses.
AB  - Quality teaching requires insights into learners' perceptions of the subject
      matter and those professionals who use it. Practitioners can benefit from
      knowledge of how they are perceived generally in society, which provides insight
      into their own performance. In a paper related to this one, the authors generated
      data about science and scientists from 229 short stories about science by
      Australian secondary students. The findings were similar to other image research
      about scientists and science. The authors then surveyed literature about the
      image of nurses and nursing. This revealed strongly contrasting images for
      science/scientists and nurse/nursing. This paper documents the contrasts and
      explores the implications for science educators working in Schools of Nursing.

PMID- 8260778
TI  - Nurses need to debate the issue of deregulation.

PMID- 8260779
TI  - Private health care: how much choice?

PMID- 8260780
TI  - There are three main ways by which a professional journal can review manuscripts.

PMID- 8260781
TI  - The power to be different: is professionalization the answer?
AB  - Nursing, it seems, is 'professionalizing' in a period of history when some
      consider the professions to be in decline. This view is partly a reaction to the
      recognition that professionalization has only one legitimate characteristic--the
      appropriation of power. Power to control work and to control one's destiny are
      the fundamental characteristics of professions. Nursing seeks this power, yet
      simultaneously seeks to be qualitatively different to the established
      professions. This is a dilemma for nursing--to be simultaneously the same and
      different to the established professions. Professionalization, despite its
      limitations and problems may, however, be the only way of achieving the power to
      be different.

PMID- 8260782
TI  - First-line nurse managers in NSW: perceived role competencies (Part II).
AB  - A survey of 412 first-line nurse managers employed in hospitals in New South
      Wales, Australia was undertaken to determine the competencies they believed an
      individual should possess to fulfil that managerial role. Factor analyses
      identified both significant functions of the role as well as areas of role
      conflict and confusion. 13 factors were identified from 4 major scales indicating
      that first-line nurse managers perceived their role to be extremely comprehensive
      in terms of managerial knowledge and skills. The analyses clearly indicate that
      competencies related to staffing and financial issues are perceived to be
      essential to role performance. However, the correlation coefficient (factor
      loadings) indicate that ambiguity exists with competencies concerning patient
      care, perhaps as the remnants of the charge nurse role are discarded. The
      findings in this study have been presented in two parts: Part 1 discussed the
      factors identified in two scales, Functional Management and Patient Care
      Management; Part II discusses the factors identified in the remaining two scales,
      Staff Management and Leadership (subdivided into two subscales for analysis).

PMID- 8260783
TI  - Acute health care and Australia's ethnic people.
AB  - At some stage, people of non-English speaking background (NESB) living in
      Australia will require acute health care. This in itself is not particularly
      remarkable or problematic; however, as the mainstream services available to the
      community are essentially monocultural (i.e. reflect the domination of Anglo
      Australian cultural values), it is questionable as to whether the unique needs of
      Australia's culturally diverse people are being met. The discussion will focus on
      some of the problems encountered by people of NESB and/or culturally different
      backgrounds in acute health care services. Nursing as a profession defends
      rigorously the notions of holistic and morally accountable nursing practice. For
      my part, it is difficult to accept that unacceptable nursing attitudes and
      practices toward patients of culturally different backgrounds have been tolerated
      by the nursing profession--not least, in its failure to correct them, and by
      virtue of its silence which has, until recently, tacitly validated them. While it
      might be said that the case studies presented here are few and limited, I am sad
      to say that there are many other similar examples (see Johnstone & Kanitsaki
      1991a, Kanitsaki 1989a, 1983, Parsons 1990). Certainly these cases 'speak for
      themselves' in depicting a range of unacceptable nursing behaviours.

PMID- 8260784
TI  - Aboriginal health.
AB  - Improving the health of Australian Aborigines remains a challenge for health care
      professionals. Understanding the meaning of the term health is central to this
      issue. There are cultural differences that must be considered, and here the
      traditional Aboriginal view of health is compared with that of the World Health
      Organization.

PMID- 8260785
TI  - The importance of assessment.

PMID- 8260786
TI  - Reflective practice in critical care nursing.

PMID- 8260787
TI  - Nurses and independent fee-for-service practice: a critical view.
AB  - A contemporary development in nursing in Australia is the move to independent
      private practice. This move is made in support of autonomy for the individual
      nurse practitioner and in the interests of improved patient care. This paper
      examines this development using the literature as data and critical theory as the
      framework of analysis. Critical theory argues that much human knowledge is bound
      by 'ideological' interests in either the technical or interpretative.
      Emancipatory knowledge attempts to peel off the various ideological layers in
      search of truth. Using work to examine the 'technical interest' and
      professionalism to examine the 'interpretative interest', it is argued that in
      the contemporary Australian health care system the nurse's claim to autonomy
      through independent practice calls for continuing debate and reflection.

PMID- 8260788
TI  - Well! What are you doing on Saturday afternoon?

PMID- 8260789
TI  - The need for continuing education.

PMID- 8260790
TI  - Nurses and aboriginal health workers: a more meaningful partnership.

PMID- 8260791
TI  - Identification and characterization of the iron compounds in bone marrow by means
      of Mossbauer spectrometry.
AB  - In order to determine and to demonstrate the cellular iron molecular states in
      hematopoietic bone marrow, direct investigations were performed by means of
      different and complementary spectroscopic techniques: optical absorption,
      electron spin resonance and Mossbauer spectrometry. In fact, the latter appears
      to have been the most informative. In addition to the hemoglobin forms, five- and
      six-coordination ligand protoporphyrins IX (monomeric and polymeric stacking,
      respectively) were observed. A small amount of non-hemic high-spin iron III
      storage component (ferritin) was measured. No diferric transferrin was detected.
      A ferrous compound was also observed and attributed to the mitochondrial iron
      pool.

PMID- 8260792
TI  - Plasma esterase activities in rats fed magnesium-deficient diets.
AB  - In a study with rats it was determined whether dietary magnesium concentration
      affects plasma esterase activities. The feeding of a diet with 0.01% (w/w)
      instead of 0.04% magnesium reduced plasma magnesium concentration by 50%. Plasma
      total esterase, arylesterase and butyrylcholinesterase activities were
      significantly decreased in the magnesium-deficient rats. In rats fed a diet
      containing 0.02% magnesium, plasma magnesium concentration was lowered by 30%,
      and group mean plasma total esterase activity was decreased, but not the
      activities of arylesterase and butyrylcholinesterase.

PMID- 8260793
TI  - The nutritional selectivity of a siderophore-catabolizing bacterium.
AB  - The ability of a siderophore-catabolizing bacterium to assimilate ferric ion was
      examined. While the bacterium utilizes the siderophore deferrioxamine B (DFB) as
      a carbon source, it was incapable of using the ferric ion analogue (ferrioxamine
      B) as an iron source. It did, however, assimilate the ferric ion of the chelator
      ferric nitrilotriacetic acid and of the siderophore ferrirhodotorulic acid
      (ferriRA). Neither ferriRA nor its deferrated analog (RA), however, were capable
      of functioning as carbon sources for the bacterium. The microbe thus employs a
      'nutritional selectivity' with respect to these two siderophores. That is, it
      does not use the siderophore it employs as a carbon source (DFB) as an iron
      source nor does the siderophore utilized as an iron source, i.e. ferriRA, nor its
      deferrated analog (RA), serve as carbon sources for the organism.

PMID- 8260794
TI  - Turnover rate of metallothionein and cadmium in Mytilus edulis.
AB  - The results demonstrate the first attempt to determine metallothionein turnover
      in the whole soft tissues of mussels Mytilus edulis exposed to cadmium. Half
      lives for metallothionein and cadmium are 25 and 300 days, respectively. As
      metallothionein degrades the released cadmium induces further synthesis of the
      protein, to which the metal becomes resequestered. The slow metallothionein
      turnover rates (compared with mammals) and the lack of significant cadmium
      excretion testify to the relatively stable nature of the cadmium-metallothionein
      complex in these invertebrates and supports the view of a detoxifying role for
      metallothionein in the mussels.

PMID- 8260795
TI  - Caring: a new framework for analysis.
AB  - The increased attention given to the concept of care within the nursing
      literature must be considered in the light of the relatively superficial
      consideration given to the same concept within the educational curriculum. This
      article offers possible explanations for such brief consideration before
      discussing the development of a new framework for analysis of care.

PMID- 8260796
TI  - Fetal tissue transplantation in Parkinson's disease.
AB  - Parkinson's disease is the most prevalent degenerative neurological disorder.
      Although fetal tissue transplantation offers new hope for sufferers, it has
      created moral and ethical dilemmas that require careful consideration by
      patients, health professionals and, indeed, the whole of society.

PMID- 8260797
TI  - Treating a miner with underground phobia.

PMID- 8260798
TI  - Defining nursing practice.
AB  - Nursing needs definition. The UKCC has recently proposed three levels of nursing
      practice: primary, clinical nurse specialist and advanced practitioner. This
      article examines these roles and illustrates the level of attainment required in
      relation to wound care.

PMID- 8260800
TI  - Stricter control needed over private nursing homes.

PMID- 8260799
TI  - Understanding paracetamol.
AB  - It is easier than we may think to overdose inadvertently on paracetamol. With
      another winter upon us, many cold remedy products now carry a manufacturer's
      warning; however, do nurses themselves fully understand why paracetamol can be so
      fatal?

PMID- 8260801
TI  - First-aid management of psychological emergencies: 1.
AB  - Psychological emergencies are complex events whose management requires
      considerable skill on the part of the nurse aider. This article, the first in a
      series on the management of psychological emergencies, outlines the main areas of
      assessment and the nurse-aid management of a psychologically disturbed person.

PMID- 8260802
TI  - Planning and resource allocation in NHS colleges of health studies: 1.
AB  - The rapidly changing environment in which NHS colleges of health studies are now
      operating presents tremendous challenges to leaders in nurse education. Financial
      constraints brought about by the internal market and rapidly changing technology
      have resulted in complex funding arrangements and incompatible planning cycles.
      In the first of two articles, the funding of nurse education is explained and the
      recent changes in funding for NHS colleges are explained.

PMID- 8260803
TI  - What future for a regional nurse?

PMID- 8260804
TI  - When can the law be disobeyed?

PMID- 8260805
TI  - Measuring the prevalence and incidence of pressure sores.
AB  - There is increasing interest in measuring the prevalence and incidence of
      pressure sores. These terms are often poorly understood and sometimes used
      interchangeably, although they refer to different forms of data collection. This
      article seeks to clarify the differences between them.

PMID- 8260806
TI  - GABAergic neurons and their role in cortical plasticity in primates.
AB  - GABA neurons and GABA receptors are conspicuous elements of cerebral cortical
      organization. They serve to shape the stimulus-response properties of neurons in
      the sensory areas and undoubtedly play a comparable role in the nonsensory areas
      as well. Although non-GABAergic local circuit neurons exist in the cerebral
      cortex, the variety of forms adopted by the GABAergic neurons and their important
      functional role have served to focus attention on the latter in investigations of
      local cortical circuitry. In primate neocortex, GABAergic neurons constitute
      approximately 25-30% of the neuronal population. In addition to their known or
      postulated functions in shaping neuronal receptive fields and response profiles,
      some of which are still controversial (Sillito, 1984; Ferster, 1986), their
      transmitter, GABA, and the major class of receptor upon which it acts are
      regulated in an activity-dependent manner even in the adult (Jones, 1990). In
      this, there is a potential mechanism for the plasticity of representational maps
      that is demonstrable in somatic sensory, motor, auditory, and visual cortex
      (Merzenich et al., 1983; Sanes et al., 1988; Robertson and Irvine, 1989; Kaas et
      al., 1990).

PMID- 8260807
TI  - Circuitry, architecture, and functional dynamics of visual cortex.
AB  - A fundamental understanding of the mechanisms of cortical processing requires an
      examination of the relationships of cortical circuitry, functional architecture,
      and receptive field properties. Ultimately, this kind of analysis can be utilized
      to explore the neurobiological basis of psychophysics and perception. At the
      onset our studies were intended to account for the then known receptive field
      properties of cortical cells in terms of their underlying circuitry, but
      surprisingly a good part of the cortical circuit appeared to be in violation of
      the principles of cortical architecture, and this led us to explore the
      possibility of new, more complex properties of cortical cells. It has become
      increasingly possible to relate the responsive specificity of cortical cells, and
      the circuitry underlying this specificity, to the perceptual capabilities of the
      visual system by performing analogous experiments on single cells and in human
      psychophysics.

PMID- 8260808
TI  - Minicolumnar activation patterns in cat and monkey SI cortex.
AB  - The distribution of stimulus-evoked 14C-2-deoxyglucose (2DG) labeling in primary
      somatosensory cortex (SI) of monkey (Macaca fascicularis) and cat was
      investigated. Reconstructions of the global pattern of labeling reveal that
      discrete skin stimuli evoke activity within an extensive region of SI, and that
      the activation pattern typically consists of multiple, elongated regions of above
      background labeling ("modules," typically 0.5-1.0 mm wide, and 1-4 mm long).
      Evidence obtained using recently developed methods (Tommerdahl, 1989) for
      quantitative analysis of 2DG activity patterns is shown to be consistent with the
      idea (Whitsel et al., 1991) that SI modules typically are bounded by zones
      dominated by stimulus-evoked inhibition. The labeling pattern within individual
      2DG modules in SI of both cats and monkeys is analyzed quantitatively (in the
      frequency domain). Within-module spatial activation patterns are demonstrated to
      be periodic, consisting of radially oriented profiles of above-background
      labeling separated from each other by less strongly labeled radial profiles. The
      spectral characteristics of within-module 2DG labeling change systematically with
      location along the module's long axis: spatial frequencies between 18 and 35
      cycles/mm are prominent in the labeling that occupies both the middle and upper
      layers at central locations in the module, but are a less obvious component of
      the labeling in both the middle and upper layers at locations remote to the
      module center. Since the radially oriented periodic variation both (1) in 2DG
      labeling in regions of SI outside modules and (2) in optical density in images of
      Nissl-stained sections of SI consists predominantly of spatial frequencies in the
      range of 18-35 cycles/mm, it is concluded that the radial profiles of labeling
      within individual 2DG modules correspond to groupings of minicolumns
      distinguishable from their neighbors on the basis of labeling intensity. The
      findings raise the possibility that highly structured, within-module spatial
      patterns of SI minicolumnar activation encode information about the physical
      properties of tactile stimuli.

PMID- 8260809
TI  - Form, function, and intracortical projections of neurons in the striate cortex of
      the monkey Macacus nemestrinus.
AB  - Single neurons were recorded in the striate visual cortex (area 17) of the old
      world monkey Macacus nemestrinus. Eight pyramidal neurons, seven spiny stellate
      neurons, two basket cells, a clutch cell, and a chandelier cell were filled
      intracellularly with HRP. Their receptive fields were consistent with previous
      single-unit studies. Their axonal arbors were less elaborate than in equivalent
      neurons in the cat, but the laminar specificity of the boutons was very much more
      precise in the monkey than in the cat. Nevertheless, the basic cortical circuits
      in cat and monkey appear to be very similar.

PMID- 8260810
TI  - Thalamocortical organization in the cerebello-thalamo-cortical system.
AB  - In the cat, the cerebellum projects via the ventroanterior-ventrolateral (VA-VL)
      complex of the thalamus to the motor and premotor cortices and also to the
      parietal association cortex. Cerebellar inputs to each of these regions have been
      characterized electrophysiologically by depth profiles of cortical potentials
      following stimulation of the brachium conjunctivum and of the VA-VL complex, and
      morphologically by the laminar distribution of thalamocortical (TC) terminations,
      in aggregate and at the single-axon level. One population of TC neurons
      terminated mainly in layer I and was associated with late surface negative
      potentials. A second population, with terminations in layers III and IV, was
      associated with early deep negative potentials. Terminations in layer III of the
      motor cortex formed multiple patches about 1-1.5 mm wide (mediolateral), which
      aligned to form 2-5 mm stripes extended rostrocaudally. This pattern correlates
      with the configuration of individual TC axons, which have two to six separate
      terminal patches distributed over 6 mm (rostrocaudal). The wide morphological
      divergence of single TC axons in the cortex may imply functionally multiple
      innervation of different efferent columns. Alternately, along with other inputs,
      it may permit a highly dynamic output selection from multiple representations,
      for example, of a variety of muscle groups in different combinations.

PMID- 8260811
TI  - Intrinsic synaptic organization of the motor cortex.
AB  - Recent anatomical and electrophysiological studies of the intrinsic synaptic
      circuitry of the motor cortex are revealing novel aspects related to the
      functional organization of this cortical area. These studies demonstrate that the
      motor cortex is composed of modules consisting of columnar aggregates of neurons
      related to different aspects of the same movement. Excitatory and inhibitory
      connections of intracortical origin link neurons within each of these cortical
      modules, and also mediate interactions between different cortical modules located
      as far as 2-3 mm from each other. The intrinsic excitatory connections utilize
      glutamate, and act via both NMDA and non-NMDA postsynaptic receptors. The
      intrinsic inhibitory connections are GABAergic. Intrinsic cortical circuits are
      involved in the temporal coordination of different cortical modules for the
      execution of complex movement patterns. In addition, the intrinsic inhibitory and
      excitatory connections are involved in the plasticity of representation zones in
      the motor cortex, a phenomenon that occurs following nerve damage or during the
      acquisition of novel motor skills.

PMID- 8260812
TI  - Confocal microscopic study of the dendritic organization of patchy, intrinsic
      neurons in area 18 of the cat.
AB  - The intrinsic, horizontally projecting neurons in visual cortex are organized
      into discrete clusters, or patches. While earlier studies focused on the
      organization of the patches and their relationship to functional properties, such
      as orientation tuning and binocularity, little is known about the detailed
      morphology of the neurons in these patches. We retrogradely labeled patches of
      local, intracortical neurons (local patch neurons) by in vivo injections of
      fluorescent dextrans into area 18, then iontophoresed Lucifer yellow into
      prelabeled cells in lightly fixed cortical slices, and examined the dendritic
      morphology of local patch neurons in layer 2/3 of area 18 by confocal laser
      scanning microscopy. Most of the neurons we examined were spiny pyramidal
      neurons, including modified pyramids, small to moderately large standard
      pyramids, and star pyramids. Smooth, multipolar cells of the basket and bipolar
      cell types were also present. The basal dendritic trees of more than 60% of the
      local patch pyramidal neurons in layer 2/3 displayed mediolaterally elongated
      dendritic fields. This finding appears to be specific for pyramidal neurons, as
      our sample of smooth, multipolar neurons did not show this trend.

PMID- 8260813
TI  - Specific and columnar projection from area TEO to TE in the macaque
      inferotemporal cortex.
AB  - The organization of connections from area TEO to TE was studied by the use of the
      anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). Single or, in one
      case, two small injections of the tracer were made in the lateral part of TEO.
      Labeled terminals were found in restricted regions of TE within two to five dense
      foci. In these foci, terminals were distributed beyond the middle layers to form
      a columnar cluster elongated vertical to the cortical surface. This specificity
      of connections may derive from an organization that is feature specific rather
      than retinotopic. Single axons reconstructed from the columnar foci showed
      heterogeneous features in the laminar distribution. Arbors of some axons were
      localized in the superficial layers, and those of other were in the middle
      layers.

PMID- 8260814
TI  - Development of forward and feedback connections between areas V1 and V2 of human
      visual cortex.
AB  - We have determined the sequence in which forward connections between visual
      cortical areas V1 and V2, and feedback connections between V2 and V1 develop in
      humans. For this purpose Dil was injected into V1 and V2 of postmortem brains of
      different pre- and postnatal ages. The laminar distribution of labeled fibers and
      cell bodies in V1 and V2 indicates that forward and feedback connections emerge
      shortly before birth. The development of both pathways proceeds over several
      postnatal months such that the laminar termination pattern of forward connections
      appears relatively mature before feedback connections reach their mature form. At
      37 weeks of gestation both forward and feedback connections originate exclusively
      from deep-layer neurons, which extend axons in deep layers only. By 9 d
      postnatal, forward connections from V1 to V2, in addition to layers 5 and 6, also
      arise from neurons in layer 4B of V1. At this stage for the first time forward
      fibers enter layer 4 at the topographically appropriate location of V2. At 9 d
      postnatal most feedback fibers from V2 still occupy deep layers of V1 but many,
      through interstitial growth, elaborate vertical sprouts at regular intervals
      along the length of horizontal axons. As feedback connections mature, distal
      segments of horizontal axons are pruned back to branch points and fibers assume L
      shaped configurations. By 7 weeks of age forward fibers from V1 enter V2 through
      deep and superficial layers and provide input to layers 3 and 4. At this stage
      feedback fibers from V2 have entered layer 4B of V1. By 4 months of age forward
      connections have assumed all the laminar characteristics of mature connections;
      that is, they arise from layers 2/3, 4B, 5, and 6 of V1, and terminate in layers
      3 and 4 of V2. In sharp contrast, at 4 months of age feedback connections to V1
      are still immature, showing terminations in layers 4B, 5, and 6 but no input to
      layer 2/3. The protracted postnatal emergence of feedback connections is similar
      to that of local long-range connections within layer 2/3 of V1 (Burkhalter et
      al., 1993). Since both of these circuits are thought to provide information about
      the context in which objects are seen, it is interesting to speculate that the
      late onset of texture segmentation in infants (Atkinson and Braddick, 1992;
      Sireteanu and Rieth, 1992) may be related to the postnatal maturation of specific
      intracortical circuits.

PMID- 8260815
TI  - Gap junctional communication and the development of local circuits in neocortex.
AB  - In the neocortex, as well as in many other brain regions, neurons responding to
      similar stimulus features are usually found close to one another. Here we examine
      the possible role of gap junctional communication in forming and defining these
      local neuronal groupings, examples of which may be the columns found in the
      neocortex of virtually all mammalian species. We have approached this question
      experimentally in cortical brain slices using calcium imaging to visualize
      multicellular activity patterns, and tracer injections to identify the anatomical
      pattern of gap junction coupling in the developing neocortex. Our results suggest
      that dendrodendritic gap junctional communication may be involved in the
      formation of local connectivity, most likely by synchronizing electrical or
      biochemical activity among neighboring neurons.

PMID- 8260816
TI  - Neuronal birth and death.
AB  - Neurogenesis and cell death occur predominantly during the postnatal period in
      the dentate gyrus of the rat. Recent studies have shown that mitosis and
      apoptosis in this system are regulated by adrenal steroids, possibly through
      excitatory amino acids. Studies performed in other systems have identified genes
      that mediate cell birth and death, which may also participate in the development
      and maintenance of the dentate gyrus.

PMID- 8260817
TI  - Reciprocal Schwann cell-axon interactions.
AB  - This article describes the reciprocal interactions between neurones and Schwann
      cells with particular reference to the role of growth factors and neurokines as
      signalling molecules between these cells and of the extracellular matrix as a
      conduit for such signalling. Major recent advances have identified molecules
      produced by neurones that are responsible for Schwann cell proliferation, as well
      as some of the Schwann cell factors regulating the expression of molecules shown
      to play an important role in neuronal survival and differentiation.

PMID- 8260818
TI  - Transcriptional regulation of the development of neurons and glia.
AB  - The past year has seen significant progress in the analysis of transcriptional
      regulation as it relates to neural development. Highlights include the
      identification and analysis of new homeobox genes that delimit developmental
      boundaries in the vertebrate forebrain, the study of upstream regulators of
      homeobox genes, the analysis of Pax genes that may contribute to specification of
      the vertebrate dorso-ventral neuraxis, and the functional analysis of
      transcription factors that are likely to specify particular neural cell types in
      both vertebrate and invertebrate nervous systems.

PMID- 8260819
TI  - Adhesion molecules of the nervous system.
AB  - The structural and functional characterization of neural cell-cell adhesion
      molecules continues to progress at a rapid rate, exposing the complex nature of
      these large multidomain receptors and their intricate relationship with the cell.
      Over the past year, significant progress has been made in the description of
      multiple binding activities, signaling potentials, and cytoplasmic associations
      of cell-cell adhesion molecules. In addition, new modes for developmental
      regulation of adhesion molecule function have been identified.

PMID- 8260820
TI  - Proteoglycans in the nervous system.
AB  - Proteoglycans are ubiquitous cell-surface and secreted glycoproteins that are
      involved in diverse cellular behaviors. The identities of several nervous system
      proteoglycans, including many of the major species in the mammalian brain, have
      recently come to light. In addition, recent studies have given new insights into
      the roles of proteoglycans in nervous system development and function.

PMID- 8260821
TI  - Axonal transport and the cytoskeleton.
AB  - Great advances in the field of axonal transport have been made in the past year,
      including the identification of new molecular motors associated with microtubules
      and actin. In addition, studies on the mechanisms of bidirectional fast axonal
      transport have clarified new aspects of this process, such as the isolation of a
      kinesin-binding protein, kinectin, and the finding that phosphorylation regulates
      kinesin's dissociation from membranous organelles. New approaches to studying
      slow transport of cytoskeletal proteins have provided further evidence that the
      axonal cytoskeleton in mammalian systems is largely stationary, although a
      dynamic exchange occurs between polymers and a small pool of moving subunits.

PMID- 8260822
TI  - The postsynaptic density.
AB  - The postsynaptic density is a specialization of the nerve cell's submembrane
      cytoskeleton that is hypothesized to participate in the regulation of synaptic
      adhesion, transmitter receptor clustering, and modulation of receptor
      sensitivity. Until recently, many of the major proteins in the highly insoluble
      postsynaptic density fraction remained uncharacterized. Modern immunological and
      microsequencing methods now make it possible to define more precisely the
      molecular composition and function of this intriguing organelle.

PMID- 8260823
TI  - Methods for ablating neurons.
AB  - This past year, laser ablation has been applied to investigations of
      neuromuscular connectivity in Drosophila, neuronal function in nematode, and
      mammalian central nervous system development. Ablation by targeted gene
      expression has been refined and applied to questions of neural development.
      Chromophore-assisted laser inactivation has been used to demonstrate distinct
      functions for two proteins during grasshopper neural development.

PMID- 8260824
TI  - Postnatal gene transfer into the central nervous system.
AB  - Substantial progress has been made in the development of techniques for the
      expression of foreign genes in the central nervous system of postnatal animals.
      Fetal and adult brain cells and other cells, including fibroblasts and muscle
      cells, have been successfully employed as vehicles for foreign gene expression in
      the central nervous system. Direct gene transfer strategies, such as those using
      herpes and adenoviral vectors, are presently under intense and fruitful
      investigation.

PMID- 8260825
TI  - Trinucleotide repeat expansions in neurological disease.
AB  - During the past year, new examples of human neurological disease have been
      discovered that have an unprecedented type of mutation as their cause: the
      remarkable expansion of trinucleotide repeats. These triplet repeats are normally
      polymorphic and exonic, though not always coding. In disease states they become
      markedly unstable and may expand moderately or by thousands of repeats in a
      single generation, influencing gene expression, message stability or protein
      structure.

PMID- 8260826
TI  - Mitochondrial cytopathies.
AB  - Defects of the mitochondrial respiratory chain and mutations of mitochondrial DNA
      have now been associated with a wide range of human diseases. The precise
      pathogenetic mechanisms by which these biochemical abnormalities induce tissue
      dysfunction are not understood. The identification of a mutation in the proline
      anticodon and in the 12S RNA genes of mitochondrial DNA are interesting new
      additions to the catalogue of pathogenetic mutations of this genome. The recent
      demonstration of nuclear complementation of mitochondrial DNA depletion provides
      the opportunity to identify nuclear genes involved in mitochondrial DNA
      replication. The possible role for mitochondrial deficiencies in certain
      neurodegenerative diseases and in the ageing process have given additional
      momentum to research in this area. Treatment for the mitochondrial 'cytopathies'
      remains disappointing and improvement in this area awaits a better understanding
      of their aetiology.

PMID- 8260827
TI  - Virus-cell interactions in the nervous system and the role of the immune
      response.
AB  - The outcome of a viral infection within the nervous system depends on a complex
      interplay between the virus, its target cell and the immune system. Recent
      research has elucidated a variety of mechanisms involved in these interactions
      and their role in the production of disease.

PMID- 8260828
TI  - Human T-cell leukaemia virus type I and neurological disease.
AB  - Tropical spastic paraparesis is thought to be caused either directly by human T
      cell leukaemia virus type I (HTLV-1), or by the immune response to the virus.
      Recent work has identified differences between tropical spastic paraparesis
      patients and healthy carriers of HTLV-I, both in the virus and in the host's T
      cell response to the virus. These differences may provide clues to the
      pathogenesis of tropical spastic paraparesis.

PMID- 8260829
TI  - Experimental autoimmune encephalomyelitis as a model of immune-mediated CNS
      disease.
AB  - Experimental autoimmune encephalomyelitis models are used to analyze the
      generation and organization of the myelin-specific autoimmune repertoire, and
      potential immunoregulatory loops preventing spontaneous activation of
      encephalitogenic T cells. These lymphocytes are profoundly modulated by
      infectious agents, which may trigger, or more commonly, prevent experimental
      autoimmune encephalomyelitis. The development and resolution of the pathogenic
      central nervous system infiltrations is controlled by locally produced cytokines
      that cause recruitment of infiltrate cells, and their disappearance. Several of
      the new findings seem now to be applicable for therapeutic strategies, especially
      with the aim of interfering with immunospecific recognition steps involved in
      disease generation.

PMID- 8260830
TI  - Ciliary neurotrophic factor as an injury factor.
AB  - This article reviews recent evidence suggesting that endogenous ciliary
      neurotrophic factor may be involved in neural responses to injury, and discusses
      the possibility that ciliary neurotrophic factor could have therapeutic
      applications in a clinical setting. The functional relevance of ciliary
      neurotrophic factor in non-injury situations is also evaluated, with emphasis on
      its possible roles in embryonic development.

PMID- 8260831
TI  - Huntington's disease: animal models and transplantation repair.
AB  - Recent identification of the gene for Huntington's disease is currently
      attracting widespread attention. While having importance for predictive testing
      and the potential of elucidating the underlying disease process, this discovery
      does not yet provide any advances for therapeutic intervention. Here we review
      recent advances in the development of improved animal models of Huntington's
      disease and strategies for its repair. Novel toxins may better mimic the
      neuropathology, and provide important clues about the underlying metabolic
      disorder, of the human disease. In addition, recent experiments into the cellular
      morphology, development and function of striatal cell transplants in both rats
      and monkeys are now indicating the prospect of viable strategies for structural
      repair in this disorder.

PMID- 8260832
TI  - Strategies for rescue of retinal photoreceptor cells.
AB  - A variety of genetic and environmental factors cause degeneration of retinal
      photoreceptors. This review focuses on current strategies to rescue defective,
      but still viable, rods and cones, including transplantation of normal retinal
      pigment epithelium cells, corrective gene therapy, administration of
      survival/growth factors, protection from the damaging effects of light, and
      dietary supplementation of vitamin A.

PMID- 8260833
TI  - Expanding roles for the Schwann cell: ensheathment, myelination, trophism and
      regeneration.
AB  - Schwann cells show remarkable versatility in undertaking a broad repertoire of
      functions. It is now clear that the well known functions of ensheathment and
      myelination are specifically regulated by contact with axons, that the Schwann
      cell is centrally involved in extracellular matrix production in the peripheral
      nerve trunk, and that the Schwann cell plays a critical role in promoting axonal
      regeneration in the peripheral nervous system. The Schwann cell's ability to
      promote regenerative efforts in many central neurons has led to an increasing
      interest in using Schwann cell autografts for central nervous system repair.

PMID- 8260834
TI  - Neuronal and glial cell biology.

PMID- 8260835
TI  - Disease, transplantation and regeneration.

PMID- 8260836
TI  - Why dose-response relationships are often non-linear and some consequences.
AB  - Given the dependence of many risk assessments on the assumption of linearity of
      dose-response relationships in human populations, we analyze the circumstances
      likely to lead to non-linearity and test our hypothesis of the high prevalence of
      non-linearity by examination of recent literature. METHODS. The analysis of
      Bross, based on whether irradiated cells die or can manifest malignancy, leads
      him to generalize that if a single exposure can have one of two (or more)
      countervailing outcomes, non-linearity of dose-response will result. We list four
      other common mechanisms which would have similar effects: symptom-stimulated
      withdrawal from exposures to respiratory irritants; certain aspects of the
      "healthy worker effect" (especially its obverse-withdrawal from the work force
      due to illness); selected consequences of the competing risks of long-term
      disease; and shift in relative strength among multiple independent variables. We
      then examine recent literature to see how often reports of linear, monotonic, and
      non-monotonic dose-response relationships occur and discuss the likelihood of
      countervailing alternate outcomes in selected examples. RESULTS. Non-linear and
      linear relationships are about equally frequent. Under circumstances where
      countervailing outcomes are probable, dose-response relationships should be non
      linear and often are. These conditions may also lead to non-linear difference
      equations, which may manifest "chaotic" attributes. CONCLUSIONS. Regulations and
      policies cannot be routinely derived on the basis of extrapolating linear dose
      response relationships for human populations. Although our analysis is oriented
      principally to epidemiology, similar considerations apply to toxicological
      studies as well.

PMID- 8260837
TI  - In vitro percutaneous absorption of [14C] ethylene glycol.
AB  - The objective of this study was to determine the percutaneous absorption of
      ethylene glycol through human skin in vitro. The in vitro diffusion cells were of
      the flow-through design with 1 cm2 surface area. Three separate donor skin
      samples, taken from the thighs of white males, 16, 37, and 57 years old, were
      used and three replicates were performed for each experiment. Phosphate buffered
      saline, at a flow rate of three ml per hour, served as the receptor fluid. The
      human cadaver skin samples were dermatomed to 500 microns. [14C]-labeled ethylene
      glycol was applied to the skin surface in acetone vehicle at a dose of 8
      micrograms/cm2. After 24-hr dermal exposure, 18.28 +/- 11.66% of the applied dose
      was recovered in the receptor fluid, 8.29 +/- 5.02% in the skin and 12.53 +/-
      6.77% in the skin surface wash (total accountability was 39.11 +/- 7.23%).
      Individual difference existed (P < 0.05) for the three human skin sources. The
      combined skin and receptor fluid partitioning resulted in a potential absorbed
      dose of 26.57% relative to the 8 micrograms/cm2 applied dose for a 24-hr exposure
      duration. This represents a flux of approximately 2 micrograms/cm2/24 hr or 0.09
      micrograms/cm2/hr for ethylene glycol. The maximum flux observed was 2.82%/hr/cm2
      or 0.25 micrograms/cm2/hr.

PMID- 8260838
TI  - Using objective and subjective information to develop distributions for
      probabilistic exposure assessment.
AB  - The propagation of variance through complex exposure models has been simplified
      by simulation software running on desktop computers; however, the appropriate
      representation of variability in, and uncertainty about, model inputs remains a
      challenge. The U.S. Environmental Protection Agency (EPA) has indicated that the
      Monte Carlo simulation approach to exposure assessment is acceptable as long as
      input distributions are credible, i.e., rooted in fact (EPA, 1992). The use of
      distributions based on empirical evidence is certainly desirable; however, it is
      not always possible to obtain measurements for all exposure model inputs under
      the conditions of interest. Where objective evidence is scarce or unavailable,
      subjective judgments are necessary. In this work, the application of both
      statistical and subjective approaches to the development of distributions for
      exposure model inputs is explored. The consequences of one's approach to
      distribution development, on the interpretation and applicability of the output,
      are also considered.

PMID- 8260840
TI  - A wipe sampler for the quantitative measurement of dust on smooth surfaces:
      laboratory performance studies.
AB  - A flat surface wipe sampler has been developed to quantitatively measure the
      concentration (micrograms/g) and surface loading (micrograms/cm2) of dust on flat
      surfaces. The Lioy-Weisel-Wainman (LWW) Sampler has been tested under conditions
      that controlled particle deposition in a chamber for two types of particles: road
      dust and potting soil, and for three different types of surfaces: painted
      shelving, formica, and wood paneling. The results for replicate analyses
      demonstrated that the sampler had > 90% efficiency for the capture of deposited
      dust and had a coefficient of variation of < 20% for replicate samples of the
      wooden shelving and formica. The wood paneling had a higher coefficient of
      variation, although it was less than 25%, due to its porosity. Operating
      procedures are presented and illustrated, and results from a study that used the
      technique to sample chromium from residential settings are also discussed.

PMID- 8260839
TI  - An analysis of blood lead data in clinical records by external data on lead pipes
      and age of household.
AB  - This study examined the possibility that lead pipes in the drinking water
      distribution system were elevating the blood lead levels of children in London,
      Ontario, Canada. Based on their postal codes, 164 children admitted between 1984
      and 1989 to an institution for the behaviorally disordered or developmentally
      challenged were categorized according to whether they lived in the area of the
      city known by the local Public Utilities Commission to be serviced by lead pipes.
      Analysis of covariance was used to obtain confounder-adjusted geometric means in
      each area. After adjusting for gender, year of lead test (a surrogate for
      gasoline source), and census tract prevalence of low family income, children in
      the lead service area (LSA) were found not to have higher blood lead levels
      (geometric means: LSA = 4.7 micrograms/dl, Non-LSA = 4.8 micrograms/dL; p =
      0.839). The average blood lead level declined 60.9% between 1984 and 1989. Using
      municipal tax assessment data on the age of each child's home, those children
      living in homes built during or before 1945 (when interior paints were as much as
      50% lead by dry weight) had an average blood lead level that was 62.3% higher (p
      = 0.011) than that of those in homes built since 1975 (when interior paints were
      limited to no higher than 0.5% lead by dry weight). A clear gradient was
      observed. This association with age of home remained significant after adjusting
      for gender, diagnosis, and year of lead test. Variables indicating the amount of
      industry near the child's residence and the presence of lead service pipes did
      not enter the model after house-age. In conclusion, no evidence indicated that
      the lead service pipes were elevating blood lead levels in these London children.
      The data suggest that with the removal of lead from gasoline, lead-based paint is
      a significant remaining source of lead exposure. Little data are available on
      childhood lead exposure from paint in Canada. The present descriptive data
      suggest that more research into this potential problem in Canada is warranted.

PMID- 8260841
TI  - Distributions of total skin surface area to body weight ratios for use in dermal
      exposure assessments.
AB  - Surface area to body weight ratios were calculated for three age groups of the
      population using direct measurement data reported in the scientific literature. A
      strong negative correlation was observed between these ratios and age, and ratios
      did not differ as a function of sex. Distribution data for surface area to body
      weight ratios are presented for three age groups. Because of the strong
      correlation between these two factors, the use of these distributions in human
      exposure/risk assessments using point estimation techniques and/or Monte Carlo
      simulations may be more appropriate than treating surface area and body weight as
      independent variables.

PMID- 8260842
TI  - Linking a PBPK model for chloroform with measured breath concentrations in
      showers: implications for dermal exposure models.
AB  - Four issues are addressed in this paper. First, both dermal uptake models and a
      revised PBPK model are developed and combined into a form appropriate for
      simulating chloroform breath levels in individuals exposed in showers by
      inhalation and dermal routes and by the inhalation route only. Second,
      experimentally measured and previously reported ratios of chloroform
      concentrations in air and breath to tap-water concentration are used to evaluate
      the model predictions. Particular attention is given to the implied dermal uptake
      as measured by these experiments and to whether this is consistent with the
      recommended value for skin uptake of chloroform that is calculated using EPA
      guidance. This analysis indicates that the ratio of chloroform dermally absorbed
      in the shower relative to tap-water concentration is between 0.25 and 0.66 mg per
      mg/L and that the effective permeability of the skin during a 10-min. shower
      exposure is between 0.16 and 0.42 cm/hr. Third, the model is used to assess the
      relationship of dermal and inhalation exposure to metabolized dose in the liver.
      It is found that, for dermal and inhalation exposures in the shower and under
      conditions of linear metabolism, the ratio of metabolized dose to water
      concentration is on the order of 0.41 mg per mg/L. Fourth, the model is used to
      determine the chloroform concentration at which dermal and inhalation exposures
      to chloroform would begin to result in nonlinear metabolism. This concentration
      is found to be in the range of 60 to 100 mg/L.

PMID- 8260843
TI  - Bird droppings contain endotoxin and (1-->3)-beta-D-glucan.
AB  - Samples of bird droppings were collected and the amount of endotoxin and (1-->3)
      beta-D-glucan in these was determined using a specific Limulus assay. All samples
      contained these agents and calculations on airborne levels demonstrated that
      doses at risk for inflammation and allergic alveolitis were present. Endotoxin
      and (1-->3)-beta-D-glucan should be considered in investigations on lung disease
      induced by bird droppings.

PMID- 8260844
TI  - Autoantibodies and clinical rheumatic complaints in two children of women with
      silicone gel breast implants.
AB  - Considerable interest and efforts are directed at determining the extent to which
      silicone gel breast implants may contribute to the risk of developing autoimmune
      disease. There is also comparable interest in determining the extent to which
      silicone may alter the natural history of an established autoimmune disease.
      Recently, there has been concern over the possibility that children of women with
      silicone breast implants might somehow be adversely affected because of either
      trans-mammary or trans-placental delivery of silicone during either breast
      feeding or pregnancy. Herein, we describe two children of mothers with silicone
      breast implants, both female, aged approximately 3 and 9 years, both of whom had
      long-standing myalgias that were unexplained and did not fit current clinical
      criteria for juvenile arthritis. Both were found to have positive antinuclear
      antibodies. Additionally, the 9-year-old girl was found to have a significantly
      high titer of antibodies against denatured human type II collagen; indeed, her
      titer was six standard deviations above the mean for normal controls. There have
      been numerous previous studies which have documented an adverse impact of trace
      metals, chemicals and some medications on the morphologic and neurologic
      development of children exposed in utero. Much less information exists on
      potential toxicity experienced by a neonate through breast feeding, although
      examples of toxic transmission have been reported. In Western Europe, but not the
      United States, women with silicone breast implants are advised not to breast
      feed. Further research should address these concerns and, in particular, women
      with silicone breast implants, with evidence of leakage or rupture, should
      refrain from breast feeding until further data are obtained.

PMID- 8260845
TI  - Novel genes in the human major histocompatibility complex class-II region.
AB  - Recent studies have identified a number of new genes mapping to the class-II
      region of the human major histocompatibility complex. Functionally these can be
      grouped into three broad categories: those encoding the new class-II-related
      genes DMA and DMB; those involved in aspects of class-I antigen-processing and
      presentation, and those with no apparent association with the immune system.
      There is evidence that further factors involved in class-II antigen presentation
      are located in the DMB to DQB1 interval.

PMID- 8260846
TI  - Blood transfusion as a means for transmission of retrovirus-induced
      lymphoproliferative disease in mice.
AB  - Lymphoproliferative disease was elicited in C57BL/6KH and (BALB/c x C57BL/6)F1
      hybrids by a single intraperitoneal injection of 10(5) FFU of LP-BM5 virus
      preparation. The disease could reproducibly be transferred by a single
      intravenous transfusion of 0.2 ml of whole blood as well as 0.1 ml of blood
      cells, plasma or serum from the infected animals. F1 hybrids displayed a delayed
      development of the disease when an acellular virus preparation was administered,
      but they were fully susceptible to the disease when syngeneic blood from infected
      F1 donors was transfused. Blood from donors in the prodromal stage was as
      effective in transmission of the disease as blood from donors with fully
      developed disease. This indicated that in murine lymphoproliferative disease
      viremia develops very early in the course of the disease. It seems that using the
      blood transfusion one could develop a reliable semiquantitative assay for the
      infectiveness of the animals suffering from LP-MB5-induced lymphoproliferative
      disease.

PMID- 8260847
TI  - Cell-free Fc-gamma receptor III in sera from patients with systemic lupus
      erythematosus: correlation with clinical and biological features.
AB  - Fifty patients (41 females and 9 males, ranging in age from 12 to 79 years) with
      systemic lupus erythematosus (SLE) and 20 normal controls were evaluated for the
      presence of plasma cell-free Fc gamma receptor III (Fc gamma RIII) using an ELISA
      based upon a sandwich of two monoclonal antibodies. The standard curve was
      obtained with serial dilutions of recombinant Fc gamma RIII. In the patients, the
      cell-free Fc gamma RIII levels ranged from to 1.76 micrograms/ml, while it did
      not exceed 0.21 microgram/ml in the controls. Assuming that the cutoff is 0.25
      microgram/ml, 11 SLE patients and no controls had elevated cell-free Fc gamma
      RIII levels in the serum. Among the SLE patients, the level of cell-free Fc gamma
      RIII was significantly lower (p = 0.05) in 4 patients with sicca syndrome than in
      the remaining 46. Furthermore, cell-free Fc gamma RIII levels appeared to be
      lower in 11 patients with renal involvement than in those without. For the
      biological parameters, we observed that the 27 patients who presented lymphopenia
      also had a lower level of cell-free Fc gamma RIII when compared to the 23
      patients without lymphopenia (0.09 +/- 0.19 versus 0.35 +/- 0.52 microgram/ml; p
      = 0.05). Circulating cell-free Fc gamma RIII may originate from shedding by
      presumably activated polymorphonuclear cells.

PMID- 8260848
TI  - Different elimination of circulating IgA immune complexes in rat and guinea pig.
      Blood clearance, organ distribution and cellular uptake in the liver.
AB  - Soluble IgA immune complexes, formed between 125I-labelled dinitrophenyl
      conjugated human serum albumin and mouse IgA anti-dinitrophenyl antibodies
      (MOPC315), were given intravenously to rats and guinea pigs. Blood clearance
      kinetics and organ distribution of radioactivity were measured after 15 min.
      Radioactivity was quantified in isolated parenchymal cells, Kupffer cells (KCs)
      and liver endothelial cells. IgA complexing did not affect the antigen blood
      clearance kinetics in either species. In rats, IgA increased the total hepatic
      antigen uptake, owing to a vast increase in the uptake by parenchymal cells. No
      IgA-mediated effect could be shown in KCs, still about 40-50% of the hepatic
      uptake was confined to KCs. In guinea pigs there was also an IgA-mediated
      increase in hepatic uptake, but here the increase could be ascribed to the KCs
      alone.

PMID- 8260849
TI  - Coiling phagocytosis: a way for MHC class I presentation of bacterial antigens?

PMID- 8260850
TI  - Influence of age on IgE responsiveness to Dermatophagoides farinae: an immunoblot
      study.
AB  - IgE responsiveness to Dermatophagoides farinae body extract was compared by
      immunoblotting among four groups of mite-sensitive asthmatic children: group I
      aged 0-3, group II aged 4-7, group III aged 8-11 and group IV aged 12-15. In the
      group I subjects, the 15-kD component was bound by 88% of sera and strongly by
      56% of sera. The 25-kD component was bound by 40% of sera, but most of the
      binding reactions were faint. IgE binding to other components was generally low.
      In the group II subjects, 15- and 25-kD components were bound by 96% and 56% of
      sera, 30-kD and 110-kD components by 76% and 60% of sera, respectively. In
      addition, 18-, 40-, 59- and 80-kD components were bound by more than 30% of sera.
      In group III and IV subjects, the frequencies of IgE binding to these components
      were not significantly changed as compared with those of group II subjects. The
      rabbit antisera against Der f I and Der f II specifically reacted with 25- and 15
      kD components, respectively. These results suggest that the 15-kD Der f II
      allergen is the most important antigenic constituent associated with the early
      IgE response to house dust-mites in mite-reactive asthmatic children.

PMID- 8260851
TI  - Isolation of the 36-kD German (Blattella germanica) cockroach allergen using fast
      protein liquid chromatography.
AB  - Cockroach allergens have been established as important sensitizing agents in the
      induction of asthma. In the present investigation, we identified a 36-kD allergen
      from German cockroach (Blattella germanica) using fast protein liquid
      chromatography that reacted in the Bla g II monoclonal assay developed by Pollart
      et al. Defatted whole body German cockroaches were extracted in phosphate
      buffered saline and fractionated using gel filtration (Superdex 75) and anion
      exchange (MonoQ) chromatography. The 36-kD allergen was isolated from this
      enriched allergen preparation by excision from modified preparative sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gels,
      electroelution, dialysis and lyophilization. SDS-PAGE/Western immunoblot analysis
      using a serum pool of cockroach-sensitive individuals revealed a single band. The
      lyophilized 36-kD allergen was then analyzed for amino acid composition and
      digested for peptide amino acid sequencing.

PMID- 8260852
TI  - Role of cyclooxygenase and 5-lipoxygenase metabolites, platelet-activating factor
      and 5-hydroxytryptamine in allergen-induced airway responses in the brown Norway
      rat.
AB  - We determined the effects of selective inhibition of arachidonic acid metabolism
      via the cyclooxygenase and 5'-lipoxygenase pathways using flurbiprofen and BWA4C,
      respectively, of 5-hydroxytryptamine (5-HT) using methysergide and of platelet
      activating factor (PAF) using WEB 2086 on the airway responses to ovalbumin (OA)
      aerosol in OA-sensitized Brown Norway rats. Twenty-one days after intraperitoneal
      injection of OA, rats were exposed to a 1% OA or saline aerosol. Only
      methysergide (10 mg/kg i.p.; 3 doses over 24 h) provided significant protection
      of the immediate response to OA. The increase in airway responsiveness to
      acetylcholine after OA exposure was not significantly altered by methysergide,
      flurbiprofen (10 mg/kg i.p.), BWA4C (50 mg/kg i.p.) and WEB 2086 (50 mg/kg i.p.)
      all given over 24 h prior to OA challenge. In addition, there was no effect on
      the increased recovery of eosinophils and lymphocytes in bronchoalveolar lavage
      fluid at 24 h. We conclude that 5-HT is an important mediator of the acute
      response to OA, but that 5-HT, lipoxygenase and cyclooxygenase products and PAF
      are unlikely to be involved in OA-induced airway hyperresponsiveness and
      inflammation in the Brown Norway rat.

PMID- 8260853
TI  - Antigen-induced airway hyperresponsiveness is associated with infiltration of
      eosinophils in lung tissue, but not with bronchoalveolar lavage eosinophilia or
      neutrophilia.
AB  - To examine the role of airway inflammation in airway hyperresponsiveness (AHR),
      we developed an animal model of AHR in guinea pigs and examined the
      histopathologic changes of these airways. Guinea pigs were actively sensitized
      with dinitrophenylated Ascaris suum extract and challenged with inhalation of the
      same extract. Six and 24 h after antigen challenge, airway responsiveness to
      inhaled acetylcholine (ACh), bronchoalveolar lavage fluid (BALF) and lung
      histology were studied. Airway responsiveness to inhaled ACh increased 6 h after
      antigen challenge (p < 0.05), but an increase in airway responsiveness was not
      observed 24 h after antigen challenge as determined by PC300 (the minimum
      concentration of ACh at which the respiratory resistance exceeded 300% of
      baseline value). The number of eosinophils and neutrophils in BALF increased 6
      and 24 h after antigen challenge compared to sensitized, nonchallenged guinea
      pigs, peaking at 24 h after antigen challenge. On the other hand, the numbers of
      infiltrating eosinophils in bronchial and bronchiolar tissues increased 6 and 24
      h after antigen challenge compared to sensitized, nonchallenged guinea pigs,
      peaking at 6 h after antigen challenge. We therefore conclude that AHR after
      allergen exposure in sensitized guinea pigs is associated with an increase in
      infiltrating eosinophils in lung tissue but not with BAL eosinophilia or BAL
      neutrophilia.

PMID- 8260854
TI  - Mode of action of a topical steroid on immediate phase reaction after antigen
      challenge and nonspecific nasal hyperreactivity in nasal allergy.
AB  - This study compared the effects of 2-week administration of a topical steroid
      (fluticasone propionate [FP] 100 micrograms twice daily) with placebo in 28
      patients with perennial nasal allergy who were allergic to house dust and mites
      in a double-blind randomized study. The number of inflammatory cells and decidual
      epithelial cells and concentrations of tryptase and eosinophil cationic protein
      in nasal lavages, and reactivity of the nasal mucosa to histamine and to antigen
      were investigated. The topical steroid, FP, significantly inhibited all of these
      assessments. The degree of improvement of nasal reactivity to histamine
      significantly correlated with the degree of decrease in eosinophil cationic
      protein levels.

PMID- 8260855
TI  - Possible mechanisms of airway hyperresponsiveness after late asthmatic response
      in guinea pigs.
AB  - To elucidate the mechanism of airway hyperresponsiveness after late asthmatic
      response (LAR), we analyzed bronchoalveolar lavage fluid (BALF) and examined the
      airway smooth muscle contractility to acetylcholine (ACh). On day 1 after LAR,
      there was a significant positive correlation between the number of neutrophils in
      BALF and the increase in airway responsiveness after LAR (r = 0.82, p < 0.01). In
      the in vitro study, the dose response curve to ACh was significantly shifted to
      the left after removal of the epithelium in control guinea pigs. However, in
      hyperresponsive animals after LAR, removal of the epithelium had no significant
      effect on ACh-induced response. These results indicate that infiltration of
      neutrophils and other inflammatory cells induce epithelial damage and hence the
      development of airway hyperresponsiveness after LAR.

PMID- 8260856
TI  - Treatment of secretory otitis media with local instillation of hydroxyzine.
AB  - The study is a preliminary single-blind, placebo- and prednisolone-controlled
      investigation of the treatment of 156 children with otitis media with effusion
      (secretory otitis media, SOM), ranging from 2 to 12 years. The protocol involved
      tympanotomy and placement of a ventilation tube (grommet), through which control
      or drug solutions were introduced. Other parameters and coexisting symptoms which
      could contribute to SOM were also examined. Patients were divided into 3 groups
      as follows: group A: control (normal saline, 2 ml); group B: prednisolone (25 mg
      in 2 ml); group C: hydroxyzine pamoate (10(-5) M in 2 ml). The results indicate
      that in those children treated with hydroxyzine, the rate of relapse was
      significantly reduced and so was the amount of histamine present in middle ear
      effusions. The effectiveness of hydroxyzine is discussed in the context of the
      pathophysiology of SOM, especially with respect to mast cells and their
      activation by allergic and nonallergic means.

PMID- 8260857
TI  - Clinical and immunological aspects of hepatitis B virus infection in children
      receiving multidrug cancer chemotherapy.
AB  - For two reasons hepatitis B virus infection is an important problem in patients
      with cancer. First, multidrug cancer chemotherapy may reactivate or worsen a
      previously benign chronic HBV infection. Second, patients undergoing cancer
      chemotherapy are at an increased risk of acquiring and spreading HBV which may
      result in an endemic infection. HBV reactivation may precipitate into a severe
      acute disease including fulminant hepatitis. In contrast, the acquisition of HBV
      during cancer chemotherapy commonly takes a mild clinical course but frequently
      leads to persistently high viremia. This state of immunotolerance to viral
      antigens allows viral replication without any sign of liver cell destruction.
      Withdrawal of chemotherapy does not cause significant changes if infection
      occurred during cytotoxic chemotherapy. Infection with HBV during cancer
      chemotherapy, therefore, may be considered as a model of an induced antigen
      specific immunotolerance. In agreement with this hypothesis, vaccination against
      HBV during cancer chemotherapy does not prevent spread of HBV in oncology wards
      as it does not produce significant anti-HBs titers. Furthermore, vaccination even
      suppresses the immune response to later booster doses after chemotherapy has been
      withdrawn.

PMID- 8260858
TI  - Duck hepatitis B virus (DHBV) as a model for understanding hepadnavirus
      neutralization.
AB  - The role of the immune response to the human hepatitis B virus (HBV) envelope
      proteins in neutralization of viral infectivity has been well documented. The
      similarity between HBV, prototype member of the hepadnavirus family, and the
      closely related duck hepatitis B virus (DHBV) has allowed, use of the latter as a
      convenient model for the study of molecular mechanisms of HBV replication and
      neutralization. In this brief review, we will examine the HBV and DHBV envelope
      proteins and their role as targets for virus neutralization.

PMID- 8260859
TI  - Implications of genetic variation on the pathogenesis of hepatitis B virus
      infection.

PMID- 8260860
TI  - Chronic infection in woodchucks infected by a cloned hepatitis delta virus.
AB  - Two woodchucks (Marmota monax) intrahepatically inoculated with hepatitis delta
      virus (HDV) complementary DNA clones pSVL-D3 and pSVL-Ag showed virological and
      pathological signs of acute and chronic HDV infection. HDV-RNA and hepatitis
      delta antigen (HDAg) were detected in serum by slot-blot hybridization and by
      western blot five weeks after inoculation. Liver biopsy specimens collected at
      8th week post inoculum were positive for HDV-RNA. Anti-HDV antibodies were
      detected at the 11th and 9th weeks, respectively. Histological finding of
      hepatocarcinoma and persistence of circulating HDV-RNA and anti-HDV were observed
      up to the 10th month. Both woodchucks produced "small" and "large" HDAg antigen,
      although the inoculated cloned DNA bears the coding capability solely for the
      small antigen. A transient decrease of woodchuck hepatitis virus DNA (WHV-DNA)
      level was observed during the peak of HDV infection. Successive inoculation of
      acute-phase serum in three woodchucks resulted in a successful infection in one
      of the animals.

PMID- 8260861
TI  - Hepatitis B virus C-gene variants.
AB  - The heterogeneity of hepatitis B virus (HBV) is increasingly believed to play a
      role in viral persistence, pathogenesis, and the type of response to antiviral
      therapy. One of the best studied parts of the HBV genome is the C-gene which
      codes for the nucleocapsid protein (HBc) and the e-antigen (HBeAg). Here we
      attempt to review the recent data on the sequence heterogeneity of this region
      and its possible implications.

PMID- 8260862
TI  - Long-term response to interferon therapy in chronic hepatitis B: importance of
      hepatitis B virus heterogeneity.
AB  - The long-term therapeutic efficacy of alpha IFN and the influence of preC
      variants on the type of response were evaluated in 25 patients with chronic
      hepatitis B, 14 HBeAg and 11 antiHBe positive patients, treated with alpha IFN
      and monitored for at least four years after discontinuing therapy. In both groups
      of patients, serum HBV-DNA became frequently undetectable by DNA dot blot during
      treatment, suggesting that alpha IFN has an antiviral effect both on HBeAg and
      antiHBe positive chronic carriers. However, long term follow up showed that the
      loss of viral DNA in antiHBe carriers was only transient, because all responder
      patients relapsed from 1 to 48 months after IFN withdrawal. In the HBeAg positive
      carriers, selection for preC mutants was observed at the end of follow up in 2
      patients who seroconverted to antiHBe and remained viremic. Both the frequent
      occurrence of reactivations in antiHBe compared to HBeAg carriers, and the
      association of IFN therapy with preC mutant virus selection during long term post
      treatment follow up observed in this study, indicate that preC variants are more
      resistant to IFN therapy than preC wild type HBV. Our data suggest therefore,
      that IFN therapy may be less frequently able to induce a permanent remission in
      patients infected with preC mutants.

PMID- 8260863
TI  - Significance and relevance of serum preS1 antigen detection in wild-type and
      variant hepatitis B virus (HBV) infections.
AB  - These studies assessed whether the serum expression of preS1 antigen could be a
      useful HBV marker for monitoring the progress of antiviral therapy in the
      treatment of chronic active hepatitis B (CAH-B) virus infections. Our findings
      indicate that: 1) the rearrangements we observed in the preS region of mutated
      HBV DNA molecules during chronic infection did not effect the preS1 sequence (21
      47) critical for HBV infectivity; 2) the persistence or even the rebound of preS1
      antigen expression during follow-up in responders to antiviral therapy may
      indicate virus persistence, suggesting the possibility of relapse through wild
      type HBV or the emergence of HBV variants following the immunoelimination phase.

PMID- 8260864
TI  - Complete nucleotide sequences of six hepatitis B viral genomes encoding the
      surface antigen subtypes ayw4, adw4q-, and adrq- and their phylogenetic
      classification.
AB  - The complete nucleotide sequences of six hepatitis B viral (HBV) genomes were
      determined by dideoxy chain termination sequencing of ten overlapping nucleotide
      fragments obtained by the polymerase chain reaction. Four of the genomes belonged
      to the two genomic groups E and F of HBV which have been previously identified by
      us on the basis of sequence divergences within the S gene. Genomic group E
      encodes the HBsAg subtype ayw4, group F adw4q-. The other two genomes were of
      Pacific origin within group C and encoded adrq-. The relationship of these
      complete human HBV genomes to 21 that have been previously published, together
      with one chimpanzee virus and four rodent hepadnaviral genomes, was investigated
      by constructing a phylogenetic tree utilizing a combination of distance matrix
      and approximate parsimonious methods. Thereby, the previously demonstrated
      segregation of human HBV strains into six genomic groups was confirmed. Both of
      the representatives of the groups E and F were found to differ by 8.1-13.6% and
      by 12.8-15.5% from the genomes of the other genomic groups and by 1.5 and 3.7%
      from each other. Since they differed by more than 8% from the genomes in the
      other groups, the limit originally used to define HBV, genomic groups their
      status as new genomic groups was confirmed. The two Pacific group C strains were
      found to differ by 2.7% from each other and by 4.1 to 5.4% from other group C
      genomes, suggesting that they diverged early from the other group C genomes.
      According to both the overall similarity and the phylogenetic dendrogram the F
      strains formed the most divergent cluster of HBV genomes favoring the concept
      that they represented the original HBV strains of the New World. The next split
      in the dendrogram segregated the A, D, E and the chimpanzee strains from the
      Asian B and C strains. Information on the nucleotide sequences and their encoded
      products of HBV strains of different genomic groups will provide a basis to
      understand biological variations of the HBV infection in different parts of the
      world.

PMID- 8260865
TI  - Role of IgM antibody to hepatitis B core antigen in the diagnosis of hepatitis B
      exacerbations.
AB  - IgM anti-HBc levels were measured by the IMx Core-M Abbott assay in 939 serum
      samples in order to define a specific and sensitive cut-off value for diagnosis
      of chronic hepatitis B. The sera used were obtained from 52 chronic HBV patients
      and 10 HBV carriers with HCV or HDV co-infections and 155 asymptomatic subjects
      without evidence of liver disease. A Youden index value of 95.4% with 98%
      sensitivity and 97.4% specificity was obtained for an IMx Index value of 0.204 as
      cut-off. A one-year follow-up study with monthly tests has shown that
      quantitative analysis of IgM anti-HBc can serve as a noninvasive tool for
      monitoring HBV infection, and provides an accurate diagnosis of hepatitis B
      exacerbations. Significant elevations of IgM anti-HBc levels were associated with
      hepatitis B exacerbations in 96.2% of the cases but with none of the ALT flare
      ups observed in HCV or HDV infected individuals. These results suggest that
      quantitative analysis of IgM anti-HBc provides the highest degree of confidence
      in definition of spontaneous and therapy-induced exacerbations or remissions of
      hepatitis B.

PMID- 8260866
TI  - Isolate antibody to hepatitis C virus core antigen (C22) by RIBA-2: correlation
      with HCV-RNA and anti-NS5.
AB  - The presence of circulating hepatitis C virus genome (HCV-RNA), elevated ALT
      levels and antibodies to an NS5-derived synthetic peptide have been examined in
      13 subjects with isolate positivity for antibodies to the HCV core antigen (C22)
      on RIBA-2 testing. All subjects were followed up for 8-18 months (mean 12.4
      months). In seven subjects (54%), intermittent or persistent viremia was
      associated with abnormal ALT levels (6 subjects) and with positivity for
      antibodies to NS5-peptide (6 subjects). On the other hand, in 6 out of 13
      subjects (46%) no viral replication, no liver cytonecrosis and no antibodies to
      NS5 were found. It is concluded that isolate reactivity to C22 by RIBA-2 is a
      heterogeneous condition that corresponds to two distinct categories of subjects:
      those with active HCV infection and those without evidence of virus replication.
      Although HCV-RNA determination is the most reliable means of identifying HCV
      carriers, antibodies to NS5 can be a useful marker of virus activity. In fact,
      antibodies to NS5 were detected in 6 out of 7 viremic patients, compared to 0 out
      of 6 non-viremic patients (P = 0.004). It remains to be elucidated whether the
      isolate reactivity to core antigen found in non-viremic subjects represents a
      specific, HCV-induced antibody response, or is an unrelated crossreactivity.

PMID- 8260867
TI  - Is HCV transmitted by the vertical/perinatal route?
AB  - Hepatitis type C is the major aetiological cause of both parenterally transmitted
      and cryptogenic, sporadic or community acquired nonAnonB hepatitis. The lack of
      known parenteral risk factors in a consistent number of cases with nonAnonB
      hepatitis has stimulated the search of other possible modes of viral
      transmission. The aim of this report is to review the evidence both for and
      against vertical/perinatal transmission of HCV from anti-HCV positive mothers to
      infants.

PMID- 8260868
TI  - Detection of replicative intermediates of viral RNA in peripheral blood
      mononuclear cells from chronic hepatitis C virus carriers.
AB  - Clinical and experimental evidence suggests the possible existence of one or more
      extrahepatic sites of HCV infection. In order to demonstrate the "in vivo"
      infection of lymphoid cells by HCV, we applied a nested PCR to total cytoplasmic
      RNA extracted from fresh or cultured peripheral blood mononuclear cells (PBMCs)
      of HCV chronically infected patients, using primers derived from the highly
      conserved 5' untranslated region of the HCV genome. The presence of virions in
      PBMCs occurs frequently, if not always, and is often accompanied by active viral
      replication. Moreover, the appearance of replicative intermediates after
      stimulation of cellular growth with mitogens suggests that latent genomes could
      undergo replication upon cellular activation and/or proliferation.

PMID- 8260869
TI  - Multiple viral infections in HIV-infected children with chronically-evolving
      hepatitis.
AB  - Hepatic involvement was investigated in 31 children with perinatal HIV-1
      infection, who were followed for 2-82 months (mean 30.5). Liver disease, as
      revealed by increased aminotransferase levels, liver biopsy or necroscopy, was
      diagnosed in 18 children (58%), of which 7 (22.5%) had acute hepatitis and 11
      (35.5%) showed chronic liver disease. Overall, 40 persistently active or
      recurrent viral infections, as demonstrated by positive culture and/or detection
      of serum DNA, specific IgM, IgA and high levels of IgG, were revealed in the
      children with liver disease, while 12 similar infections were detected in 13
      children without liver disease (p < 0.001). In particular, the children with
      liver disease showed a significantly (p < 0.002) higher incidence of
      cytomegalovirus (CMV) infections than children without liver disease (13 versus
      3). Moreover, hepatitis C and B virus infections were revealed only in children
      with liver disease (5 and 1 patients, respectively). Clinical outcome showed a
      significantly (p < 0.001) higher mean survival in the children without liver
      disease than those with liver disease (47.5 versus 18.2 months). In fact, nine of
      the children with liver disease (50%) died, as opposed to only one of the
      children without liver disease (7.7%; p = 0.01). Based on these findings, liver
      disease is indicative of a poor prognosis in children with HIV infection, being
      related to the presence of multiple active viral infections.

PMID- 8260870
TI  - Lymphoblastoid interferon in chronic hepatitis C patients who were "non
      responders" to recombinant interferon alpha (rIFN alpha).
AB  - The aim of this study was to investigate whether there is a variable
      responsiveness of the hepatitis C virus and/or of the affected host to different
      types of interferon. We treated 21 patients affected by chronic hepatitis C who
      failed to respond to recombinant alpha interferon, after a four-month interval,
      with lymphoblastoid interferon. Alanine transaminase (ALT) serum level was normal
      in 9 patients (43%) at the end of treatment. At the end of a 12 months treatment
      free follow-up serum ALT remained normal in 3 patients, 4 patients relapsed and 2
      dropped-out. As yet there are no reports of differences in the therapeutic
      efficacy of the two types of interferon used in our study. The good response to
      the lymphoblastoid interferon in our non responders to recombinant alpha
      interferon may be due to the immune modulation induced by the four-month wash-out
      interval between the two therapies or to a different virus sensitivity to this
      interferon.

PMID- 8260871
TI  - Non responders to interferon therapy among chronic hepatitis patients infected
      with hepatitis C virus.
AB  - We studied a series of 268 chronic hepatitis C patients (31 chronic persistent
      hepatitis CPH, 69 mild chronic active hepatitis CAH, 125 severe CAH, and 43
      active cirrhosis) enrolled from 1988 to 1991 in different therapeutic protocols
      using lymphoblastoid or recombinant interferon (IFN) at a dosage of 3 mega units
      (M.U.), three times a week for 12 months. Of these patients 54.8% showed a
      complete response (normalization of aminotransferases), 14.2% a partial response
      (decrease in aminotransferases of over 50%), 27.6% no response, and 3.4% a
      substantial progressive increase in the liver enzymes during IFN (becoming
      worse). The prevalence of non responders was lower in CPH (9.7%) than in CAH
      patients (31.9% in the mild form and 20.8% in the severe), and significantly
      higher in patients with cirrhosis (53.5%). No correlation was observed between
      non response and the baseline aminotransferase level or the patient's sex.
      Patients under 35 had a better response to IFN when compared with patients 36-50
      years. This is probably due to the higher prevalence of CPH patients with a good
      response to IFN in the youngest group. No effect was gained in non responders by
      increasing the dose or shifting from recombinant to lymphoblastoid IFN; three
      patients were then treated with steroids, but only one benefitted. For 5 of the 9
      patients who became worse, steroids were started after discontinuation of IFN
      therapy, and they induced a favorable response only for the 3 who had developed
      autoantibodies during IFN treatment.

PMID- 8260872
TI  - Antibodies to interferon alpha in patients.
AB  - A massive amount of information on interferons (IFNs) has been gathered since
      their original description as antiviral agents in 1957. Human IFNs have now been
      used clinically for over a decade and their therapeutic efficacy has been well
      established for some human neoplasias and viral diseases. During these studies,
      it has also been documented that some of the patients treated with IFNs can
      develop antibodies to IFNs which can affect their therapeutic efficacy. Here, it
      is summarized what is currently known on the biological and clinical aspects of
      these antibodies.

PMID- 8260873
TI  - Patterns and mechanisms of hepatitis B/hepatitis D reinfection after liver
      transplantation.
AB  - Viral recurrence is the limiting factor in orthotopic liver transplantation (OLT)
      for hepatitis B virus (HBV) related liver disease. In fact, high rates of HBV
      infection of the transplanted liver are reported, followed by the recurrence of
      liver disease in a high percentage of cases. The importance of reinfection
      stimulates the study of its modalities and mechanisms in order to better identify
      preventive measures and better select patients for OLT. In HBV and HDV positive
      patients, the outcome of liver transplantation appears significantly better than
      in patients that are solely HBV positive, in spite of a high rate of HDV
      reinfection. Long-term analysis (5 years) of HBV and HDV infection, using the PCR
      technique, in 15 patients transplanted for an HBV/HDV positive liver disease and
      treated with anti-HBs immunoglobulin (HBIG), revealed that all patients
      experienced an HDV reinfection, but only about 7 were still harboring the virus
      after four years of follow-up. HDV reinfection was either associated to HBV
      reinfection or isolated whereas no cases of HBV isolated reinfection was
      observed. Isolated HDV reinfection was frequent and transient in all but one case
      that was superinfected by HBV. Infected peripheral blood mononuclear cells seem
      to be implicated in HBV superinfection of HDV infected liver. Liver damage was
      observed only in cases of HBV/HDV co-infection, suggesting that, in vivo, HBV is
      necessary to produce liver damage although it is not essential for HDV absorption
      to target cells, HDV penetration of these cells or HDV genomic replication. In
      addition, in isolated HDV infection, transient HDV viraemia and its low levels
      suggest that, perhaps in these patients HDV uses a very limited presence of HBV
      or alternative ways which are not efficient enough for envelope production. These
      data suggest that, particularly in HDV positive patients, antiHBs Ig
      administration, which has previously been proven to significantly reduce HBV
      reinfection in HBsAg-positive patients, may be useful in changing the natural
      history of repetition of the original viral infection and liver disease after
      OLT.

PMID- 8260874
TI  - In vitro culture systems for hepatitis B and delta viruses.
AB  - The development of tissue culture technology has led to invaluable information in
      many fields of modern virology. Until recently, the lack of an in vitro culture
      system for the hepatitis B virus (HBV) was a considerable impediment to the study
      of its life cycle at the cellular and molecular levels. However, it did not
      prevent its isolation and molecular cloning. Such has been the case also for the
      hepatitis delta virus (HDV), the genome of which was cloned and sequenced before
      its replication could be observed in cultured cells. In recent years, tissue
      culture systems for HBV and HDV have been developed progressively by the
      identification of permissive, established cell lines for production of virions
      and susceptible primary hepatocyte cultures for infection assays. I will briefly
      review here the recent experiments that have contributed to replicate HBV and HDV
      in cell culture systems.

PMID- 8260875
TI  - Susceptibility of human liver cell cultures to hepatitis C virus infection.
AB  - To develop a cell culture system susceptible to infection by hepatitis C virus
      (HCV), human fetal hepatocytes, grown in serum-free medium, were inoculated with
      serum samples from two HCV-infected patients. Viral RNA sequences were detected
      by polymerase chain reaction, using primers specific for the 5' noncoding region
      of HCV, in extracts prepared from the hepatocyte cultures as early as 5 days
      after inoculation. Virus was also released from the infected cells into the
      medium. The HCV strains could be serially passaged three times into fresh liver
      cell cultures using intracellular virus as inoculum. Evidence that HCV
      replication really took place in primary human fetal hepatocytes was also
      obtained by detection of minus-strand viral RNA (replication intermediate) in
      cell extracts and of viral antigens in the infected cells.

PMID- 8260876
TI  - Molecular basis of the diversity of hepatitis B virus core-gene products.
AB  - All hepatitis B viruses examined to date code for at least two different core
      gene products which are referred to as the c- and the e-protein. In the case of
      the human hepatitis B virus, they are known as the HBcAg and the HBeAg. Although
      these proteins share most of their primary amino acid sequence, they exhibit
      quite distinct properties. The e-protein is located in the cytoplasm and the
      nucleus of infected cells and very efficiently assembles into nucleocapsids. By
      contrast, the e-protein does not form particles. It enters the secretory pathway
      and is actively secreted by the cells. Here we describe the biosynthetic pathways
      by which the c- and e-proteins are expressed and summarize recent data from our
      laboratory showing that the antigenic and biophysical properties which
      distinguish the HBeAg from the HBcAg are primarily due to the 10 amino acid long
      portion of the HBeAg leader sequence that remains attached to the HBeAg after
      cleavage.

PMID- 8260877
TI  - Characterization of the endogenous protein kinase activity of the hepatitis B
      virus.
AB  - During the assembly of the nucleocapsid of the hepatitis B virus a protein
      kinase, probably of cellular origin, is encapsidated. This enzyme phosphorylates
      serine residue(s) localized within the lumen of the particle. By using purified,
      liver-derived core particles, we characterized the protein kinase activity in the
      presence of different ions and inhibitors. Controls were performed with cAMP
      dependent protein kinase (PKA) and protein kinase C (PKC) and recombinant core
      particles. We showed that the endogenous protein kinase of the core particles was
      not inhibited by H89, a specific inhibitor of PKA. Staurosporine, a selective
      inhibitor of PKC inhibited the endogenous kinase activity only within the first
      minutes of the reaction. In contrast, quercetine, a selective inhibitor of the
      protein kinase M (PKM) did not inhibit during the first minutes but inhibited
      efficiently during later phases of incubation. PKM represents an enzymatically
      active proteolytic fragment of PKC. These results suggest that PKC is
      encapsidated into human core particles and is converted to PKM during the in
      vitro reaction. This conclusion implies the association of a protease activity
      localized with the HBV nucleocapsid inside liver-derived core particles.

PMID- 8260878
TI  - The hepatitis B virus X gene product transactivates the HIV-LTR in vivo.
AB  - It has previously been shown that the hepatitis B virus (HBV) X gene product,
      HBx, transactivates homologous and heterologous transcriptional regulatory
      sequences of viruses, including the human immunodeficiency virus type 1 (HIV1)
      long terminal repeat (LTR), and various cellular genes in vitro. To evaluate the
      transactivating function of HBx in vivo, we generated transgenic mice carrying
      the X open reading frame under the control of the human antithrombin III (ATIII)
      gene regulatory sequences. These mice express the 16 Kd HBx protein in the liver,
      as demonstrated by immunoprecipitation studies. Crossbreeding of HBx mice with
      transgenics carrying either the chloramphenicol acetyl transferase (CAT)
      bacterial or the lacZ reporter gene driven by the HIV1-LTR allowed us to
      demonstrate, for the first time, the in vivo transactivating function of HBx
      protein.

PMID- 8260879
TI  - Accumulation of a cellular protein bearing c-myc-like antigenicity in hepatic and
      non-hepatic delta antigen expressing cells.
AB  - Patients with chronic but not acute hepatitis delta virus infection undergo a
      strong accumulation of a protein of cellular origin which specifically reacts
      with a panel of anti-c-myc antibodies and which is expressed in the same nuclei
      that express the delta antigen. In this paper we report on the in vitro
      characterization of this phenomenon. The delta antigen induced c-myc antigen
      accumulation can occur in vitro upon transfection of HBsAg positive and negative
      cell lines with HDAg expression vectors. Using recombinant vaccinia viruses
      expressing only p24 or p27 we demonstrate that structures common to the two
      isoforms of HDAg are responsible for the phenomenon, which is not restricted to
      cells of hepatic origin.

PMID- 8260880
TI  - Duck hepatitis B virus infection, aflatoxin B1 and liver cancer in ducks.
AB  - The association between chronic infection by hepadnaviruses isolated from human
      (HBV), woodchuck (WHV), ground squirrel (GSHV) and development of hepatocellular
      carcinoma (HCC) in their respective hosts is well established (reviewed in [11,
      15, 17]). By contrast, the association of duck hepatitis B virus (DHBV) infection
      with HCC is less documented. Pekin ducks congenitally infected with DHBV and
      followed for several years throughout the world do not develop liver tumors: HCC
      has been found only in domestic ducks from a single area of China, Qidong.
      Several factors such as DHBV carrier rate, breed and age of ducks, subtype of
      DHBV and environmental carcinogens are suspected to contribute to this striking
      difference between the geographical repartition of liver cancer in DHBV-carrier
      ducks. In this brief review we will consider successively the role of these
      different factors in duck liver oncogenesis.

PMID- 8260881
TI  - Cell mediated immune response to hepatitis B virus nucleocapsid antigen.
AB  - A coordinated and efficient development of humoral and cell-mediated immune
      responses is believed to be required for complete eradication of viral
      infections. During the course of hepatitis B virus (HBV) infection, the HLA class
      II and class I-restricted T cell responses to HBV nucleocapsid antigens are
      vigorous in patients with acute infection who succeed in clearing the virus but
      weak or totally absent in patients with chronic persistence of the virus. These
      findings suggest a role for these responses in the pathogenesis of hepatitis B
      and in HBV clearance. Molecular analysis of T cell recognition of the HBV
      nucleoprotein defines the presence of immunodominant core epitopes recognized by
      helper and cytotoxic T cells that may represent the starting point for the design
      of alternative strategies for prevention and treatment of HBV infection.

PMID- 8260882
TI  - [The translation symmetry in cell mosaics of amphibian embryonic ectoderm as a
      manifestation of their modular structure].
AB  - A theoretical proposition that the cell mosaics possess translation symmetry has
      been experimentally confirmed by scanning electron microscopy of the common frog
      embryonic ectoderm. This symmetry is a manifestation of the tissues modular
      structure and it provides new data for quantitative estimation of composition and
      structure of tissue morphofunctional element as well as for diagnostics and
      prediction of tissue development.

PMID- 8260883
TI  - [Variability in the completeness of posttraumatic skin regeneration in warm
      blooded animals].
AB  - It is generally accepted that skin regeneration in warm-blooded animals always
      results in scar formation. Still we have found that the skin regenerated in place
      of full-thick square skin wounds often resemble the normal one rather than the
      connective tissue scar by structure. Morphological variability of the skin
      regenerates proved to depend on the wound location and the animal species. The
      possibility of formation of the skin derivatives (hair follicles, fat and sweet
      glands, skin folds) has been shown. A classification of the skin regenerates has
      been proposed. Numerous examples demonstrate the skin ability to give rise to
      organ-specific regenerates with the morphological features specific for the wound
      site.

PMID- 8260884
TI  - [The key mechanisms of radiation hormesis].
AB  - The different cellular responses to high (suppressive) and low (stimulant) doses
      of atomic radiation suggest understanding of radiation hormesis, since the well
      developed mechanisms of damaging effect of atomic radiation (radiodamage of DNA,
      chromosomal aberrations, death of radiosensitive cells) cannot explain the
      converse effects of low stimulant radiation doses. Here the direct or indirect
      excitation of membrane receptors comes to the foreground. The excitation
      activates membrane-bound enzymes which control many vitally important processes.
      Now that an increasing proportion of the general population is exposed to low
      chronic doses of ionizing radiation, the knowledge of radiation hormesis acquires
      great importance, particularly, for temporal predictions of its consequences.
      Although this problem is far from complete understanding, it is, undoubtedly,
      wrong to estimate the hazard of the low radiation doses by straight extrapolation
      of the data obtained with much higher doses and during shorter time periods.

PMID- 8260885
TI  - [Selenium in the medicinal plants of the flora of Russia].

PMID- 8260886
TI  - [The ontogeny of additional saccules in the orifice of the cheek pouches in
      hamsters (Phodopus campbelli Thomas, 1905 and Phodopus sungorus Pallas, 1773): a
      morphometric analysis].
AB  - Time changes in functional activity of the recently described additional sacs in
      the orifice of cheek pouches (AS) has been studied in one-month-old and adult
      Phodopus sungorus and P. campbelli. The most intense AS growth and increase in
      their secretory activity falls on the second decade of the first month. It
      coincide with transition to their own feeding by coarse crust. Although there is
      no sexual dimorphism in the AS mass or the amount of their secret, time pattern
      of growth is different in males and females. Stabilization of the main indices of
      AS functional activity, their relative mass and amount of secret, at the adult
      level occurs in females earlier than in males. Adults of both species do not show
      sexual dimorphism by the both studied indices, but breeding females have both
      absolute and relative mass of AS and its secret significantly increased. As a
      whole the obtained data agree well with the previous studies (Vasil'eva,
      Feoktistova, 1993) that have demonstrated the importance of AS secret in
      survival, normal growth and development during the first month of P. campbelli.
      The described time pattern of the AS activity in ontogenesis seem to reflect the
      real need in the secret at the early age in small hamsters, and the increased AS
      activity in lactating females can be considered as a functional adaptation that
      compensate the secret deficit.

PMID- 8260887
TI  - [Hypoxia and ethanol: the comparative aspects of a study].
AB  - Metabolic effects of hypoxia and ethanol on the cell has been comparatively
      studied. The obtained data suggest their similar molecular-cellular mechanisms.
      One of the main disturbing effects of both hypoxia and ethanol is disruption of
      the cellular energy metabolism. It is related to restricted electron transport
      function of mitochondrial respiratory chain at the level of the first enzyme
      complex, which inhibits oxidation of the pyridine-dependent substrates, causes
      hyper-reduction of the NAD-dependent part of the respiratory chain, and
      significantly decrease the ranges of ATP synthesis during oxidative
      phosphorylation. The experiments were carried out on male and female white
      mongrel rats. The influences of oxygen deficiency and ethanol on the organism
      were studied on a decompression chamber model of hypobaric hypoxia and on
      isolated perfused heart. Pre-exposition of the animals in conditions of moderate
      hypoxia as well as preadministration of low ethanol dose proved to significantly
      enhance individual resistance to acute hypoxic hypoxia. Not only preventive
      action of moderate ethanol doses enhance the resistance to hypoxia, but also the
      converse preventive treatment by light hypoxia might improve state of the
      organism during alcoholic intoxication.

PMID- 8260888
TI  - [The role of the parasympathetic nervous system in regulating the kinetics of the
      regional blood circulation in the digestive system organs].
AB  - Cranio-bulbar part of the parasympathetic nervous system proved to be important
      for regulation of the blood flow distribution between the organs of the
      gastroduodenal complex (liver, stomach, and small intestine), rate of the local
      blood flow and its kinetics. Investigation of the blood supply of the above
      mentioned organs various periods (1-60 days) after bilateral subdiaphragmatic
      truncal vagotomy has demonstrated the most pronounced transformations in macro-
      and micro-hemodynamics in the 14-30 days period. Time pattern of these changes
      has one maximum in liver and stomach (14-30 days) and two maxima (7 and 30 days)
      in small intestine.

PMID- 8260889
TI  - [Human circadian rhythms and the work and rest regimen: the hypothesis of the
      "coiled spring"].
AB  - Studies of human free-running circadian rhythms have been reviewed. The
      conditions of development of free-run of the circadian rhythms were considered.
      On the basis of these data a hypothesis of "compressed spring" was proposed. It
      claims that the human circadian rhythms synchronized within the 24 h day are
      instable and related to physiologic tension. It follows that in conditions of
      relative isolation (long-term space flight, submarine navigation, polar
      expedition), during the transition period after a trans-meridian flight, and
      during adaptation to a shift (especially, night) work it is advisable to arrange
      a work-rest schedule on the basis of a prolonged 25 h day.

PMID- 8260890
TI  - What constitutes a "cure" in lymphoma?

PMID- 8260891
TI  - Non-Hodgkin's lymphoma of the spleen.
AB  - Although the spleen is frequently involved in disseminated non-Hodgkin's lymphoma
      (NHL), splenic presentation as the initial or only site of disease is uncommon.
      The true incidence of splenic lymphoma is difficult to estimate because of the
      variable definition of this disease, however, the diagnosis of primary lymphoma
      of the spleen should be limited to involvement of only the spleen and splenic
      hilum. Using this restricted definition, our experience suggests that the
      prognosis of NHL of the spleen, when pathologically staged, may have a favorable
      prognosis which approximates that seen with limited stage NHL at other sites. The
      influence of pathologic subtype on natural history and the impact of adjuvant
      therapy are discussed.

PMID- 8260892
TI  - The role of Bcl-2 in the pathogenesis of B chronic lymphocytic leukemia.
AB  - At least three categories of genes are envisaged to be involved in the natural
      history of B-CLL. First, the genes that are responsible for the transforming
      event(s) in the (presently unknown) target cell; second, the gene(s) that help
      the progressive accumulation of malignant cells and finally the gene(s) that
      cause the progression toward a more aggressive lymphoma. The possibility that the
      clonal expansion of B-CLL is due to a prolonged life-span of monoclonal B cells
      rather than to an acceleration of their proliferative activity may now be
      reinterpreted by taking into account some recent findings on the expression of
      Bcl-2 gene in B-CLL cells. The Bcl-2 gene product regulates programmed cell death
      and a number of experiments suggest that Bcl-2 is involved in the selection and
      maintenance of long-lived memory B cells rescuing them from apoptotic death and
      leading to their accumulation in the GO phase of the cell cycle. Variant
      chromosomal translocations have been detected in a small fraction (5-10%) of B
      CLL, involving Bcl-2 and the Ig light chain gene. Despite the low percentage of
      Bcl-2 rearrangements the expression of mRNA and protein is appreciable in most
      samples of fresh B-CLL cells in an amount comparable to that observed in Karpas
      422 cells, which contain a t(14;18).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260893
TI  - Detection of minimal residual disease in Philadelphia chromosome positive acute
      lymphoblastic leukemia: rationale for bone marrow transplantation from the
      polymerase chain reaction point of view.
AB  - Bone marrow transplantation (BMT) is performed as curative therapy for acute
      lymphoblastic leukemia (ALL). In most patients, BMT is performed at the time of
      remission which implies that the number of leukemic cells is less than 5% of all
      hematopoietic cells, namely, 0 to 10(10) leukemia cells in the body. Thus, some
      patients may well undergo BMT despite the fact that no leukemic cells are left in
      the body. In this respect, more accurate diagnosis of complete remission status
      would be to the patients' benefit. To detect minimal residual disease (MRD) not
      found by light-microscopy, further strategies are required after achieving
      hematological remission. Cytogenetic methods, Southern blot analysis and
      conventional immunological techniques can all provide accurate diagnosis,
      however, the sensitivity of these techniques for the detection of MRD is just as
      low as that of the light microscopy. Recently, polymerase chain reaction (PCR)
      has become available for the detection of low levels of chimeric bcr-abl
      transcripts in Philadelphia chromosome positive (Ph1) ALL patients. With this
      assay, investigators have reported MRD in patients after chemotherapy or BMT.
      Most patients who achieve hematological remission after conventional chemotherapy
      still have bcr-abl transcript detectable by PCR, confirming the general concept
      that this particular leukemia needs BMT in order to cure the disease. Some
      patients who had MRD prior to BMT continued disease free survival > 1 year after
      BMT with a negative PCR result and in these patients, MRD seems to have been
      eradicated by the BMT procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8260894
TI  - L-myc and N-myc in hematopoietic malignancies.
AB  - The myc proto-oncogenes encode nuclear DNA-binding phosphoproteins which regulate
      cell proliferation and differentiation. The c-myc gene is implicated in
      hematopoietic malignancies on the basis of its frequent deregulation in naturally
      occurring leukemias and lymphomas. Recent evidence suggests that also the N-myc
      and L-myc genes may have a role in normal and malignant hematopoiesis. N-myc and
      to a certain degree L-myc can substitute for c-myc in transformation assays in
      vitro, and their overexpression can block the differentiation of leukemia cell
      lines. Immunoglobulin heavy chain enhancer (IgH) -driven overexpression of N-myc
      or L-myc genes cause lymphatic and myeloid tumors, respectively, in transgenic
      mice. Furthermore, the L-myc and N-myc genes are expressed in several human
      leukemias and leukemia cell lines, L-myc predominantly in myeloid and N-myc both
      in myeloid and in some lymphoid leukemias. All N/L-myc positive leukemias and
      leukemia cell lines coexpress the c-myc gene, thus exemplifying a lack of
      negative cross-regulation between the different myc genes in leukemia cells.
      Taken together, these data suggest that L-myc and N-myc may participate in the
      growth regulation of hematopoietic cells.

PMID- 8260895
TI  - The role of iron and iron chelators in anthracycline cardiotoxicity.
AB  - The redox cycling of anthracyclines promotes the formation of free radicals which
      are believed to play a central role in their cardiotoxicity. A number of
      observations indicate that the mechanism of the antineoplastic effect of
      anthracyclines is independent of their cardiotoxic effect and that it may be
      possible to prevent toxicity without interfering with therapeutic effect. Iron
      plays an important role in anthracycline toxicity by promoting the conversion of
      superoxide into highly toxic hydroxyl radicals through the Haber-Weiss reaction.
      Conversely, iron deprivation by its high-affinity binding to iron chelating
      compounds may inhibit anthracycline toxicity by interfering with free radical
      formation. ICRF-187, a bispiperazonedione which is hydrolyzed intracellularly
      into a bidentate chelator resembling EDTA, is able to decrease adriamycin-induced
      free hydroxyl radical formation and to prevent the development of clinical
      cardiac toxicity in patients receiving long-term anthracycline therapy. Our
      studies in rat heart cell cultures have shown that iron overload aggravates
      anthracycline toxicity and that this interaction can be prevented by prior iron
      chelating treatment. Since iron overload caused by multiple blood transfusions
      and bone marrow failure is a common condition in patients requiring anthracycline
      therapy, these observations may have significant clinical implications to the
      prevention of anthracycline cardiotoxicity.

PMID- 8260896
TI  - Cyclosporine-induced graft-versus-host disease after autologous bone marrow
      transplantation for acute myeloid leukemia.
AB  - Rodents given cyclosporine (CSP) for several weeks after autologous or syngeneic
      bone marrow transplantation develop a syndrome that mimics allogeneic graft
      versus-host disease (GVHD). Autologous GVHD has also been reported after
      administration of CSP in patients who have received autologous bone marrow
      transplantation (ABMT) with untreated marrow for lymphoma or acute myeloid
      leukemia (AML). Our study was designed to determine whether CSP administration is
      associated with appearance of autologous GVHD in patients with AML receiving ABMT
      with 4-hydroperoxycyclophosphamide (4HC)-purged marrow and whether there was a
      dose-dependent effect of CSP on development of the syndrome. Thirty-three
      patients with AML (18 in first remission [CR1], 10 in CR2, and 5 in CR3) received
      intravenous CSP, beginning on the day of ABMT, after a preparative regimen of
      busulfan and cyclophosphamide and ABMT with 4HC-treated marrow. Skin biopsies
      were obtained weekly after ABMT or on appearance of rash and were graded for GVH
      changes. In the first phase of this study, groups of patients received CSP
      dosages of either 1 mg/kg/day (7 patients), 2.5 mg/kg/day (8 patients), or 3.75
      mg/kg/day (6 patients) for 28 days. Sixteen of the 21 patients (76%) developed
      cutaneous histopathologic grade 2 GVHD at a median of 34 days (range, 14-49)
      after ABMT, and cutaneous manifestation were present at time of positive biopsy
      in 11 of the 16 patients. There was no apparent difference in frequency, time to
      onset, or duration of GVHD among the three CSP dosage groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8260897
TI  - Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      after chemotherapy in patients with non-Hodgkin's lymphoma; a placebo-controlled
      double blind phase III trial.
AB  - To assess the clinical and hematopoietic effects of rhGM-CSF, a placebo
      controlled double blind multicenter phase III study was undertaken in patients
      with non-Hodgkin's lymphoma receiving cytotoxic chemotherapy. Sixty-two patients
      who had granulocytopenia (< 1 x 10(3)/microliters) after the first cycle of
      chemotherapy with cyclophosphamide, adriamycin, vincristine, and prednisolone
      were enrolled. After the second cycle of chemotherapy with the same regimen,
      patients randomly received either rhGM-CSF (125 micrograms/m2/day) or placebo for
      14 days (rhGM-CSF; 31 patients and placebo; 31 patients). Administration of rhGM
      CSF induced a significant increase in granulocytes mainly with neutrophils,
      eosinophils and monocytes, but elevation of lymphocytes, platelets, and
      reticulocytes was not induced. Median days of granulocytes less than 1 x
      10(3)/microliters in patients receiving rhGM-CSF were significantly shorter than
      in patients receiving placebo (p = 0.001). Adverse reactions encountered with
      rhGM-CSF, and observed in 58% of the patients were never life-threatening and
      always rapidly reversible. They included fever, nausea and vomiting, diarrhea,
      skin eruption, and malaise. These results suggest that rhGM-CSF can be safely
      administered to prevent neutropenia after chemotherapy in patients with non
      Hodgkin's lymphoma.

PMID- 8260898
TI  - Late cardiac toxicity of doxorubicin, epirubicin, and mitoxantrone therapy for
      Hodgkin's disease in adults.
AB  - Cardiotoxicity is a well recognized side effect of anthracyclines (doxorubicin
      and epirubicin) or antracenadiones (mitoxantrone) at cumulative or high doses.
      However the side effects have not been evaluated in adults with Hodgkin's disease
      who received therapeutic doses of these drugs. We analyzed the cardiac function
      studying the left ventricular ejection fraction (LVEF) at rest in 136 patients
      with Hodgkin's disease treated with doxorubicin, epirubicin or mitoxantrone used
      in combination with vinblastine, bleomycin and decarbazine. No other risk
      factors, such as radiation therapy to the mediastinum, were considered. The
      follow-up is 5 to 8 years for patients in complete remission. Forty-five patients
      received doxorubicin (from 325 to 685 mg/m2, median 475 mg/m2), 51 patients
      received epirubicin (from 310 to 610 mg/m2, median 510 mg/m2) and 40 patients
      were treated with mitoxantrone (from 70 to 165, median 125 mg/m2). The median
      time between the end of treatment and the evaluation was 6.7 years. Thirty seven
      percent of the patients (similar rates in the three groups) showed abnormalities
      in the LVEF with decreased rates independent of the drug dosage. These were
      compared with two control groups, 46 patients treated with the MOPP combination
      (mechlorethamine, vincristine, prednisone and procarbazine) or LOPP
      (chlorambucil, for mechlorethamine) and 35 healthy volunteers. We believe that
      the use of anthracyclines or antracenadione will produce late cardiac effects in
      a fraction of patients independently of the doses used and that the indications
      for these drugs be carefully monitoring so as to evaluate the development of late
      side effects.

PMID- 8260899
TI  - Autopsy findings in 47 cases of adult T-cell leukemia/lymphoma in Miyazaki
      prefecture, Japan.
AB  - To identify factors that might improve the prognosis of adult T-cell
      leukemia/lymphoma (ATL), we reviewed data on 47 autopsied cases of ATL with
      reference to the complications and cause of death. The primary cause of death was
      respiratory insufficiency due to pulmonary infection. Respiratory insufficiency
      was also attributed to the diffuse alveolar damage and pulmonary fibrosis
      resulting from chemotherapy given and oxygen. About 90% of the cases had
      infections with one or more pathogens. Cytomegalovirus (CMV) was the most
      frequent pathogen involved in 35/47 (74.5%) while fungal infections were also
      commonly seen in 25 of the 47 cases (53.2%). Of these, 17 (70%) had pulmonary
      aspergillosis. Other neoplasias were present in 10 of the 47 cases, while
      hypercalcemia was evident in 21 patients. These findings suggest that the
      prevention and treatment of nosocomial infections and of drug-induced pulmonary
      toxicity may improve the prognosis and quality of life of ATL patients.

PMID- 8260900
TI  - Induction of differentiation of myeloid leukemic cells by busulphan: in vivo and
      in vitro observations.
AB  - Treatment of a 74 year old patient with chronic myelogenous leukemia (CML) with
      busulphan resulted in an abrupt and pronounced decrease of the white blood cell
      (WBC) count with restoration of normal peripheral blood cell morphology and
      regression of splenomegaly. The Philadelphia positive (Ph+) clone was however
      still detectable. The alterations in the WBC count and morphology were not
      preceded by marrow hypoplasia but correlated closely with a marked decrease in
      the serum levels of Transcobalamin I (TC I), a vitamin B12-binding protein
      derived from immature myeloid precursors and a reciprocal rise in serum TC III, a
      vitamin B12-binding protein originating from terminally differentiated mature
      granulocytes. Studies on the HL-60 cell line showed that busulphan is capable of
      inducing leukemic cells to differentiate into granulocyte-like cells. These
      observations, taken together, suggest that in addition to its potent
      myelosuppressive effects, busulphan may induce apparent clinical remissions in
      some CML patients by promoting terminal cell differentiation.

PMID- 8260901
TI  - Childhood acute lymphocytic leukemia with a preleukemic phase: report of an
      associated translocation and review of the literature.
AB  - A fourteen month old boy presented with hepatosplenomegaly and pancytopenia. An
      extensive evaluation, including bone marrow aspiration and biopsies of both liver
      and lymph nodes, revealed a polyclonal B cell proliferation consistent with a
      reactive process, with no evidence of leukemia. After receiving transfusions of
      red cells and platelets, his blood counts recovered. Five weeks later, he
      returned with an elevated white blood count and bone marrow findings diagnostic
      of acute lymphocytic leukemia. The leukemic blasts contained a novel chromosomal
      translocation, t(5;14) (q34;q12). We describe the clinical, immunophenotypic and
      cytogenetic features of this case, review the literature of acute lymphocytic
      leukemia associated with a preleukemic phase, and discuss the relationship of
      this clinical entity to the 5q-abnormality associated with myelodysplasia.

PMID- 8260902
TI  - An unusual presentation of acute myeloid leukaemia with pericardial and pleural
      effusions due to granulocytic sarcoma.
AB  - We describe a case of acute myeloid leukaemia (Mo) presenting with pericardial
      and pleural effusions due to a granulocytic sarcoma adherent to the thymus gland
      situated in the anterior mediastinum. This has not been described previously in
      the setting of AML Mo.

PMID- 8260903
TI  - Vacuolated glycogen-laden leukemic cells in a case of crisis type chronic adult T
      cell leukemia.
AB  - We present a unique case of crisis type chronic adult T-cell leukemia (ATL), in
      which the majority of leukemic cells had abundant periodic acid-Schiff (PAS)
      positive cytoplasmic inclusions. These inclusions were found to be composed of
      glycogen because the PAS-positivity completely disappeared after digestion with
      amylase or human saliva. Electron microscopy also revealed that the inclusions
      consisted of aggregated beta particles of glycogen. The mechanism of glycogen
      accumulation in leukemic cells remains unknown; however, the presence of such
      inclusions in leukemic cells may be helpful diagnostically in T-lymphocyte
      malignancies.

PMID- 8260904
TI  - Hypertension as a paraneoplastic phenomenon in childhood Hodgkin's disease.
AB  - A 14 year old girl with Hodgkin's disease presented with hypertension as an
      unusual paraneoplastic phenomenon. The elevated plasma renin activity recorded in
      this patient was possibly a result of Hodgkin's disease. Hypertension as well as
      plasma renin activity declined to normal values following her successful response
      to chemotherapy.

PMID- 8260905
TI  - Yersinia enterocolitica meningitis and septicaemia in a patient with acute
      lymphoblastic leukaemia.
AB  - We report the first case of Yersinia enterocolitica meningitis and septicaemia
      during induction treatment for acute lymphoblastic leukaemia. The patient was
      also being treated with recombinant granulocyte colony stimulating factor and
      hence pursued an unusually mild clinical course.

PMID- 8260906
TI  - Clinical computing. A new vision of the future.

PMID- 8260907
TI  - Undiagnosed hyperthyroidism.

PMID- 8260908
TI  - Anesthetic considerations in patients with hyperparathyroidism.
AB  - Although there is controversy over which patients should undergo
      parathyroidectomy, some patients clearly benefit from the procedure. This case
      illustrates typical findings in a patient with a parathyroid adenoma.
      Preoperative hydration and electrolyte balance and selection of anesthetic drugs
      that were easily titrated was associated with a smooth intraoperative course on
      this patient. Mild hypocalcemia postoperatively was quickly recognized and
      treated.

PMID- 8260909
TI  - Complications associated with diabetes mellitus.
AB  - There is an increased risk of perioperative complications in patients with
      diabetes. Knowledge of underlying pathophysiology and assessment and appropriate
      preoperative preparation can minimize the risk. Although vigilance in monitoring
      is the key to successful outcomes in these high risk patients, cardiac arrest has
      been reported. We should anticipate this serious complication in diabetic
      patients with cardiac autonomic neuropathy.

PMID- 8260910
TI  - Acute adrenal insufficiency: a case report.
AB  - The chances of cardiovascular collapse leading to a diagnosis of Addison's
      disease are rare. One report cited 3 of 60,000 cases in which this may have
      occurred. However, it can happen and should be considered in hemodynamically
      unstable patients if the usual causes of hypotension have been eliminated. This
      is especially true in high-risk patients, ie, those who chronically receive
      steroids.

PMID- 8260911
TI  - Anesthetic management of patients with pheochromocytomas: a report of three
      cases.
AB  - The perioperative management of patients with pheochromocytoma is a challenge to
      even the most seasoned practitioner. Preoperative preparation, close monitoring,
      and anticipation of hemodynamic changes is critical for a successful outcome.

PMID- 8260912
TI  - Protamine reaction.

PMID- 8260913
TI  - Anesthetic drug interactions.

PMID- 8260914
TI  - On-line communications.

PMID- 8260915
TI  - The chemistry and pharmacology of local anesthetics.
AB  - The most common local anesthetics in clinical use today are of two classes: amino
      esters and amino-amides. These two classes differ not only in their chemical
      structure but also in regard to their metabolism and allergic potential. Potency,
      onset of action, duration of action, and relative blockade of sensory and motor
      fibers are important clinical properties of local anesthetics. These clinical
      properties are related to the physiochemical properties of lipid solubility, pKa,
      and protein binding. The effects of local anesthetics are primarily caused by the
      blockade of the sodium channels, thus affecting the slow and fast depolarization
      phase of the action potential. With the basic understanding of the chemistry and
      pharmacology of the different local anesthetic agents, the nurse anesthetist can
      more effectively integrate the use of these drugs into their clinical practice.

PMID- 8260916
TI  - Complications of regional anesthesia.
AB  - Regional anesthesia is fraught with potential risks and complications. Proper
      training and careful experience with specific techniques will go a long way to
      improve our skills. Vigilance, conscientiousness, and attention to detail are the
      qualities that will not only help us to avoid complications, but also help us to
      detect early signs of developing complications and treat them promptly. Early
      detection and treatment will improve the ultimate outcome even when complications
      do occur.

PMID- 8260917
TI  - Dosing regimens for spinal and epidural anesthesia.
AB  - Spinal anesthesia has proven to be a reliable and safe technique of major
      conduction anesthesia for nearly a century. Epidural anesthesia is being used for
      a multitude of applications in the operating room, labor and delivery setting,
      and more for the relief of postoperative analgesia. It is also noted that a
      growing number of nurse anesthetists are expanding their expertise in regional
      anesthesia to include continuous spinal, spinal techniques for infants, and
      epidural anesthesia techniques. This article reviews the physiological and
      pharmacological factors influencing the choice of anesthetic agents for major
      conduction anesthesia and the suggested dosing regimens.

PMID- 8260918
TI  - Peripheral nerve blocks.
AB  - This article addresses the use of peripheral nerve blocks as a primary or
      adjunctive technique of anesthesia for selective operative procedures. The use of
      these blocks can reduce the amount of inhalational and narcotic agents used
      during an anesthetic and facilitate a pain-free postoperative period.

PMID- 8260919
TI  - A review of chronic pain syndromes: etiology, transmission, and treatment.
AB  - This article reviews the difficulty in defining pain and chronic pain syndromes.
      A basic review of nerve transmission as related to chronic pain syndromes is
      provided. Three general chronic pain categories are developed, and the major pain
      syndromes of each category are explored. The etiology, transmission, and
      treatment of each are discussed.

PMID- 8260920
TI  - Anesthesia malpractice cases.

PMID- 8260921
TI  - Anesthetic management of a patient with sulfite sensitivity.

PMID- 8260922
TI  - Anesthetic drug interactions.

PMID- 8260923
TI  - [Tobamovirus of cruciferous plants: nucleotide sequence of genes of the transport
      protein, capsid protein, and 3'-terminal untranslated region].

PMID- 8260924
TI  - [The effect of one-time administration of atrial natriuretic factor on indicators
      of central hemodynamics and electrolyte composition of blood plasma in
      experimental arterial hypertension].

PMID- 8260925
TI  - [A system for studying the interchromosomal conversion in Drosophila
      melanogaster].

PMID- 8260926
TI  - [Status of the cellular population as criteria for the alteration and protective
      effect of pharmacoprotectors].

PMID- 8260927
TI  - [Exploratory behavior of synantropic and outdoor forms of house mice of
      superspecies Mus musculus S. lato: a comparative analysis].

PMID- 8260928
TI  - [A rapid method for removing (137)Cs from meat].

PMID- 8260929
TI  - [Similar sensitivity of neurotoxic esterase from rat and chicken brain to the
      effect of o-alkyl-o-alkylchloroformiminophenylphosphonates].

PMID- 8260930
TI  - [The effect of erythropoietin on the contractile activity of smooth muscle cells
      in the veins of rates with experimental uremia].

PMID- 8260931
TI  - [Behavior of the Campbell hamster (Phodopus Campbelli Thomas, 1905) in nature:
      confirmation of the biological signal field theory].

PMID- 8260932
TI  - Phage lambda beta protein, a component of general recombination, is associated
      with host ribosomal S1 protein.
AB  - We have purified phage lambda beta protein produced by a recombinant plasmid
      carrying bet gene and confirm that it forms a complex with a protein of relative
      molecular mass 70 kDa. Therefore, beta protein, a component of general genetic
      recombination, is associated with two functionally diverse complexes; one
      containing exonuclease and the other 70 kDa protein. Using a number of
      independent methods, we show that 70 kDa protein is the ribosomal S1 protein of
      E. coli. Further, the association of 70 kDa protein with beta protein is
      biologically significant, as the former inhibits joining of the terminal ends of
      lambda chromosome and renaturation of complementary single stranded DNA promoted
      by the latter. More importantly, these findings initiate an understanding of an
      important mode of host- virus interaction in general with specific implication(s)
      in homologous genetic recombination.

PMID- 8260933
TI  - Enhancement in gastric mucosal laminin receptor expression with ulcer healing.
AB  - The expression of gastric mucosal laminin receptor with chronic ulcer healing was
      investigated. The receptor protein was isolated from gastric epithelial cell
      membrane of rats at various stages of ulcer healing and following radioiodination
      incorporated into vesicles which exhibited specific affinity towards laminin
      coated surface. The binding assays revealed that the ulcer healing was
      accompanied by an increase in laminin receptor expression. A significant increase
      (2.5-fold) in the receptor expression occurred by the third day following the
      development of ulcer, reached a maximum of 8.6-fold increase by the 14th day when
      the ulcer was virtually healed, and its high level remained for at least 20 days.
      The results demonstrate the importance of laminin receptor as an indice of
      gastric mucosal repair in ulcer healing.

PMID- 8260935
TI  - Inhibition of hydroxyl radical-induced protein damages by trolox.
AB  - When bovine serum albumin was exposed to the hydroxyl radical generating system
      of ascorbate-EDTA-Fe3+ or ascorbate-EDTA-Fe(3+)-H2O2, carbonyl formation
      occurred. Trolox strongly inhibited the oxidative modification in a dose
      dependent manner. The fragmentation and enhancement of the proteolytic
      susceptibility of bovine serum albumin were induced by HO. only in the presence
      of O2, while trolox protected the protein against such oxidative modifications.
      In addition, inactivations of lactate dehydrogenase and creatine kinase induced
      by the hydroxyl radical were also blocked by trolox.

PMID- 8260934
TI  - Phosphorylation of a 72-kDa nucleoprotein (NP-72) in HL-60 cells is mediated by
      the double-stranded DNA-dependent protein kinase (DNA-PK).
AB  - Nuclear extracts prepared from human leukemic cells grown in the presence of cell
      differentiation-inducing agents showed a significant increase in the
      phosphorylation of a nuclear protein referred to as NP-72. The NP-72
      phosphorylation was greatly increased by the addition of purified HeLa DNA-PK and
      was reduced by the inclusion of a DNA-PK-specific monoclonal antibody to the
      assay mixture. Phosphoamino acid analysis showed serine (60%) and threonine (40%)
      residues to be the phosphate acceptors. Western blot analysis of control and TPA
      treated nuclear extracts detected multiple immunoreactive protein bands. The two
      most prominent species migrated as 300- and 210-kD proteins on SDS-PAGE, possibly
      representing an intact and a processed form of DNA-PK. The 300-kD form of DNA-PK
      was only detected in TPA-treated nuclear extracts, raising the possibility that
      cell differentiation is associated with the down-regulation and/or the inhibition
      of a protease(s) capable of regulating DNA-PK turnover.

PMID- 8260936
TI  - ATPase of Rhodospirillum rubrum requires three functional copies of beta subunit
      as determined by radiation inactivation analysis.
AB  - Radiation inactivation analysis yielded a functional unit of 170 +/- 26 kDa as
      beta subunit of ATPase was irradiated and then reconstituted to beta-depleted
      chromatophores of Rhodospirillum rubrum. A functional size of 132 +/- 17 kDa for
      the beta-depleted ATPase moiety involved in ATP hydrolysis reaction was also
      determined. When both purified beta subunit and beta-depleted chromatophore were
      irradiated separately, reconstituted, and then activity measured, the functional
      mass was 312 +/- 50 kDa. Our compelling evidence directly indicates that three
      functional copies of beta subunits were required for ATP hydrolysis.

PMID- 8260937
TI  - Enhancement of A23187-induced arachidonic acid liberation by vasopressin is
      sensitive to genistein in rabbit platelets.
AB  - A mechanism by which vasopressin enhances phospholipase A2 activation in rabbit
      platelets was investigated. Stimulation of the platelets with vasopressin
      enhanced arachidonic acid liberation, as well as aggregation and ATP secretion in
      the presence of submaximal concentration of A23187, although vasopressin alone
      had no effect. The vasopressin-enhanced liberation was inhibited by p
      bromophenacyl bromide, a phospholipase A2 inhibitor, and by genistein, a tyrosine
      kinase inhibitor. Though epinephrine also caused a similar enhancement of the
      liberation, this effect of epinephrine was insensitive to genistein.
      Staurosporine, a protein kinase C inhibitor, completely suppressed phorbol 12
      myristate 13-acetate-enhanced arachidonic acid liberation, but suppressed the
      vasopressin-induced enhancement only slightly. These results suggest that
      vasopressin-enhanced phospholipase A2 activation may be regulated by a genistein
      sensitive mechanism, most likely by a protein tyrosine kinase-mediated pathway,
      but not by guanine nucleotide-binding protein- or protein kinase C-mediated
      pathway.

PMID- 8260938
TI  - Arachidonic acid metabolism in cells transfected with sense and anti-sense cDNA
      to annexin I.
AB  - Thymic epithelial cell line TEA3A1 produce prostaglandin E2 (PGE2) and express
      high levels of annexin I. In order to study the relationship between the levels
      of annexin I expression and the arachidonic acid metabolism, TEA3A1 cells
      transfected with expression vector containing full length annexin I cDNA in
      either sense or anti-sense orientation was studied. In the anti-sense cells where
      the level of annexin I was reduced, the PGE2 production was significantly lower.
      On the other hand, PGE2 production was significantly higher in sense cells where
      the production of annexin I was also higher than in control cells. Our results
      show that increased PGE2 production in sense cells was accompanied by higher
      levels of PLA2 enzymatic activities. These results suggest that the production of
      annexin I is positively associated with the phospholipase A2 enzymatic activity
      and the prostaglandin production in thymic epithelial cells.

PMID- 8260939
TI  - Effects of multiple mutations at the conserved TATA sequence of bacteriophage SP6
      promoter on transcription efficiency.
AB  - Mutations of A<==>T were introduced individually and multiple to TATA from -4 to 
      1 of the phage SP6 promoter and their effects on transcription initiation
      efficiency measured in vitro. All 15 mutants tested were less active than the
      wild type. Mutation at -4T nearly abolishes promoter activity independent of
      other changes, and alteration at -3A reduces promoter activity substantially. On
      the other hand, effects of mutations at -2T and -1A depend on other changes,
      suggesting their role should be associated with neighboring base pairs. These
      results suggest that -4T and -3A are involved in SP6 RNA polymerase binding and 
      2T and -1A are involved in DNA unwinding. This bipartite role of the SP6 promoter
      TATA contrasts with the single role of T7 promoter TATA on DNA unwinding. The
      polymerase binding region extends further downstream in the SP6 promoter than in
      the T7 promoter.

PMID- 8260940
TI  - Studies on phosphorylated transcriptional regulator (NarL) for E. coli nar operon
      by 31P-NMR spectroscopy.
AB  - The sequential transphosphorylation from autophosphorylated nitrate-sensing
      protein (NarX) to the transcriptional regulator protein (NarL), both operating in
      signal transduction to control the expression of the respiratory nitrate
      reductase (nar) operon in E. coli, was demonstrated with an in vitro
      reconstructed system to function similarly to other bacterial two-component
      regulatory systems. Over-expression system established by means of the pT7
      promoter/polymerase provided both NarX and NarL proteins to reconstruct the in
      vitro transphosphorylation system. The phosphorylated NarL was detected, and the
      unstable phosphorylated group was directly assigned to acyl phosphate in the in
      vitro system by 31P-NMR spectroscopy.

PMID- 8260941
TI  - Chemical modification of amino groups in cardiotoxin III from Taiwan cobra Naja
      naja atra) venom.
AB  - Cardiotoxin III (CTX III), a major cardiotoxin analogue isolated from the Taiwan
      cobra (Naja naja atra) venom was modified, either with trinitrobenzene sulfonate
      (TNBS) or 4-chloro-3,5-dinitrobenzoate (CDNB). Under the conditions of limited
      reagent availability, three mono-TNP derivatives modified at Lys-5, 12, or 44,
      and three mono-CDNP derivatives at Lys-12, 23, or 44 were isolated, respectively.
      The biological activities of CTX III were more or less affected after each of
      these reactive amino groups were modified. In particular, the hemolytic activity
      to human erythrocytes and cytotoxicity on NS-1 cells of CTX III decreased to 31%
      and 50%, respectively, when Lys-12 was trinitrophenylated. More pronounced
      alteration in these activities was observed as this amino group was
      carboxydinitrophenylated. A good correlation between the hemolytic activity and
      cytotoxicity was found. These results indicate that epsilon-amino group at Lys-12
      is most closely related to the hemolytic and cytotoxic activities of CTX III. The
      antigenicity of modified derivatives still remained intact as measured by ELISA.

PMID- 8260942
TI  - Changes in cystathionine gamma-lyase levels in rat liver during lactation.
AB  - Rat liver cystathionine gamma-lyase activity increased rapidly with the onset of
      lactation, reaching a maximum value at week 2 and slowly decreasing thereafter.
      In non-lactating rats, from which the litters had been removed on the day of
      birth, the activity of this enzyme increased only minimally. The enzyme activity
      in the presence and absence of pyridoxal 5'-phosphate (PLP) did not differ
      significantly, indicating that the cystathionine gamma-lyase in lactating rat
      liver was also saturated with PLP as control rat. We then investigated whether
      the increased activity was caused by increases in the enzyme concentration. An
      antibody, prepared form purified rat liver cystathionine gamma-lyase was utilized
      for the detection of enzyme content by immunoblot analysis and enzyme
      immunoassay. On immunoblot analysis, this antibody stained purified cystathionine
      gamma-lyase, as well as staining a single polypeptide from liver cytosolic
      proteins that co-migrated with the purified enzyme at about 40 kDa. Changes in
      the staining intensity of the antibody paralleled the activity of the enzyme. The
      enzyme immunoassay showed that the content of liver cystathionine gamma-lyase at
      weeks 0, 1, 2 and 5 of lactation was 1.67, 2.33, 5.19, and 2.17 mg per g of
      liver, respectively, whereas in the non-lactating rats, the enzyme concentration
      at week 2 was found to be 2.20 mg per g of liver. The changes in enzyme
      concentration detected by enzyme immunoassay were also consistent with enzyme
      activity. We concluded that the increased cystathionine gamma-lyase activity in
      the lactating rat liver was a result of an increase in enzyme concentration.

PMID- 8260943
TI  - Structural studies on the loggerhead sea turtle (Caretta caretta) myoglobin.
AB  - The primary structure of myoglobin from the loggerhead sea turtle (Caretta
      caretta) has been determined; the protein consists of 153 amino acid residues.
      The ferric loggerhead sea turtle myoglobin has been crystallized in a form
      suitable for X-ray structural investigations. The crystals were grown at pH 8.0,
      in 0.05 M tris/HCl buffer, using 3.2 M ammonium sulfate as precipitating agent,
      at 4 degrees C, and belong to the orthorhombic space group P2(1)2(1)2(1), with
      unit cell constants a = 37.2 A, b = 61.1 A, c = 75.2 A (one molecule, 17,000
      M(r), in the asymmetric unit). A molecular replacement solution was found for the
      loggerhead sea turtle myoglobin crystals using sperm whale myoglobin structure as
      search model. The R-factor value, after molecular replacement, is 0.387, for the
      data in the 15-3.3 A resolution range. The results here reported are the basis
      for the first X-ray crystallographic investigation on a reptile myoglobin, and
      indicate a strong overall structural similarity between the loggerhead sea turtle
      and mammalian (i.e. sperm whale) myoglobins.

PMID- 8260944
TI  - Purification and characterization of a novel 46.5-kilodalton esterase from mouse
      hepatic microsomes.
AB  - A novel membrane-bound esterase was purified from mouse hepatic microsomes. The
      purified protein (ES46.5K) showed a single protein-staining band on sodium
      dodecyl sulfate-polyacrylamide gel with a minimum molecular weight of 46.5
      Kdalton. ES46.5K possessed esterase activity toward 11-acetoxy-delta 8
      tetrahydrocannabinol (11-OAc-delta 8-THC) (27.1 mumol/min/mg protein) and p
      nitrophenylacetate (119 mumol/min/mg protein), and these activities were 38 and
      47 times, respectively, as high as those of microsomes. The N-terminal amino acid
      sequence of the protein was as follows: G-K-T-I-S-L-L-I-S-V-V-L-V-A-Y-Y-L-Y-I.
      This sequence has no homology to those of the known carboxylesterases, indicating
      that this enzyme is a novel type of esterase bound to the microsomal membrane.

PMID- 8260945
TI  - Inhibition of 4-aminobutyrate aminotransferase from Pseudomonas fluorescens by
      ATP.
AB  - The enzyme 4-aminobutyrate aminotransferase (EC 2.6.1.19) isolated from
      Pseudomonas fluorescens was inhibited by the nucleotide ATP in an apparent
      competitive manner (Ki = 10.4 mM). This reversible effect was antagonized by the
      substrate GABA, whose apparent Km was increased from 0.6 mM to 2 mM in the
      presence of 20 mM ATP, suggesting that ATP interferes with GABA binding to the
      active site of the enzyme. The apparent Km with respect to the second substrate
      alpha-ketoglutarate was also increased, although to a lesser extent, whereas the
      cofactor pyridoxal 5'-phosphate was unable to influence the inhibition by ATP.
      The ATP structural analogues ADP, CTP and XTP were also able to inhibit the
      enzyme to a similar extent. These data indicate that GABA concentrations within
      the bacterial cell can be regulated by the action of ATP on 4-aminobutyrate
      aminotransferase. In addition, because the inhibition by ATP is similar to the
      inhibition of the enzyme from mammalian brain, the bacterial enzyme could provide
      a convenient source of the enzyme for studies of drug effects on brain GABA
      metabolism in vitro.

PMID- 8260946
TI  - Human corneal aldehyde dehydrogenase: purification, kinetic characterisation and
      phenotypic variation.
AB  - Human corneal aldehyde dehydrogenase (designated ALDH3) was purified to
      homogeneity and characterised with respect to substrate specificity and
      inhibition by thiol reagents. The enzyme was present as a major soluble protein
      (5% of the total soluble protein) and was found to efficiently catalyse the
      oxidation of medium chain peroxidic aldehydes which may be found in the cornea.
      These findings are consistent with the proposal that ALDH3 plays a dual role in
      the absorption of UVR and in the oxidation of peroxidic aldehydes in the
      mammalian cornea. Disulfiram did not inhibit this enzyme under the conditions
      used in this study, however p-hydroxymercuribenzoate rapidly inactivated the
      enzyme. Analysis of the proteins of the cornea and surrounding tissue indicated
      that in both the cow and the human, changes in the nature and quantity of soluble
      proteins occurred. Phenotype variants of the ALDH3 were apparent in a small
      Australian population.

PMID- 8260947
TI  - Serum-free conditioned medium of human diploid fibroblast cells contains an
      activity that stimulates prostacyclin production by cultured bovine aortic
      endothelial cells.
AB  - Serum-free culture medium conditioned by human diploid fibroblast cells
      stimulated prostacyclin production by cultured bovine aortic endothelial cells.
      Gel filtration chromatography using Sephacryl S-100HR revealed at least three
      peaks of prostacyclin-stimulating activity. This factor was relatively heat
      stable, acid-labile, trypsin-sensitive and bound to heparin Sepharose CL-6B. This
      factor was completely inhibited by indomethacin.

PMID- 8260948
TI  - Comparison of amino acid sequences of the trypsin inhibitors from taro (Colocasia
      esculenta), giant taro (Alocasia macrorrhiza) and giant swamp taro (Cyrtosperma
      chamissonis).
AB  - The amino acid sequences of the trypsin inhibitors from taro Colocasia esculenta
      var. esculenta and giant swamp taro Cyrtosperma chamissonis have been determined
      and are compared with the protein sequence of the trypsin/chymotrypsin inhibitor
      from giant taro Alocasia macrorrhiza. Both inhibitors display polymorphism and
      there is evidence of two components in the giant swamp taro. The positional
      identity between the proteins is highest at 73-75% for the comparison of the
      giant taro (GT) with the polymorphic forms of the taro (T) inhibitors and lowest
      at 56-58% for the pairs of taro and giant swamp taro (GST) proteins. The
      comparisons show that the inhibitors from T and GT are more related to each other
      than to GST, which supports their taxonomic classification into different tribes.
      Location of the P1 site for the trypsin inhibitors of aroids is different from
      that of other Kunitz-type inhibitors and could be at Leu56.

PMID- 8260949
TI  - A comparative study of erythrocyte oxalate flux rate and urinary oxalate
      excretion in hyperoxaluric rats.
AB  - The present study was carried out to investigate the relation between erythrocyte
      oxalate flux rate and the pathogenesis of calcium oxalate renal stone disease
      having hyperoxaluria as the main risk factor. Male albino rats were made
      hyperoxaluric by feeding them diets viz. vitamin B6 deficient, vitamin B6
      deficient + 51.7% galactose or fructose (serving as a sole source of
      carbohydrate), along with their respective pair-fed controls for 4 weeks. After
      28 days of feeding, oxalate excretion was in the order of vitamin B6 deficient +
      galactose > galactose control > vitamin B6 deficient + fructose > vitamin B6
      deficient > fructose control/vitamin B6 control. Whereas, transmembrane oxalate
      flux rate was in the order of vitamin B6 deficient > vitamin B6 deficient +
      galactose > vitamin B6 deficient + fructose > vitamin B6 control > galactose
      control > fructose control. No significant correlation (r = 0.304) was found
      between the urinary oxalate excretion and erythrocyte oxalate flux rates of
      various groups of rats. The study indicates that increase in oxalate excretion
      does not concomitantly increase the transmembrane oxalate flux in red blood
      cells.

PMID- 8260950
TI  - Altered lead(II)-cleavage pattern of free Phe-tRNAPhe and Phe-tRNAPhe in ternary
      complex with EF-Tu:GTP.
AB  - Pb2+ ions in sub-millimolar concentrations are known to cleave internucleotide
      bonds of phenylalanine-specific transfer RNA (tRNAPhe) from Saccharomyces.
      cerevisiae specifically between nucleotides D17 and G18 in the D-loop, with
      additional minor cleavages after D16 and G15. This makes lead(II) a sensitive
      structural probe for correct folding of tRNAPhe. In the present paper we use Pb2+
      ions as a functional probe to determine whether this part of tRNA is protected by
      the Escherichia coli elongation factor EF-Tu in the ternary complex formed
      between Phe-tRNAPhe and EF-Tu.GTP. Our results show that for tRNA in complex with
      EF-Tu:GTP, the phosphodiester bond after D17 is cleaved, yet the phosphodiester
      bonds after D16 and G15 are not. To our knowledge, this is the first time that
      Pb2+ ions, bound at a specific site in tRNA, have been used both to investigate
      the correct folding of tRNA in complex, and to footprint a functional complex
      with components whose individual structures are known.

PMID- 8260951
TI  - 99mTc-HMPAO SPECT of the brain in mild to moderate traumatic brain injury
      patients: compared with CT--a prospective study.
AB  - Single photon emission computed tomography (SPECT) with Technetium-99m hexamethyl
      propylenamine oxime (Tc-99m-HMPAO) was used in 20 patients with mild to moderate
      traumatic brain injury (TBI) to evaluate the effects of brain trauma on regional
      cerebral blood flow (rCBF). SPECT scan was compared with CT scan in 16 patients.
      SPECT showed intraparenchymal differences in rCBF more often than lesions
      diagnosed with CT scans (87.5% vs. 37.5%). In five of six patients with lesions
      in both modalities, the area of involvement was relatively larger on SPECT scans
      than on CT scans. Contrecoup changes were seen in five patients on SPECT alone,
      two patients with CT alone and one patient had contrecoup lesions on CT and
      SPECT. Of the eight patients (50%) with skull fractures, seven (43.7%) had rCBF
      findings on SPECT scan and five (31.3%) demonstrated decrease in rCBF in brain
      underlying the fracture. All these patients with fractures had normal brain on CT
      scans. Conversely, extra-axial lesions and fractures evident on CT did not
      visualize on SPECT, but SPECT demonstrated associated changes in rCBF. Although
      there is still lack of clinical and pathological correlation, SPECT appears to be
      a promising method for a more sensitive evaluation of axial lesions in patients
      with mild to moderate TBI.

PMID- 8260952
TI  - Association between patient report of symptoms after mild head injury and
      neurobehavioural performance.
AB  - Patients with closed-head injuries may have physical, affective, behavioural and
      memory problems that persist for weeks, months or years. Even patients with minor
      head trauma have been found to exhibit deficits in neurobehavioural performance.
      However, very little research has been done to examine the association between
      patient symptoms after minor head injury and neurobehavioural performance. The
      associations between five sets of symptoms (memory problems, neurological
      problems, confusion, neurasthenia and co-ordination) and five neurobehavioural
      areas (simple motor speed, response speed and attention, complex perceptual motor
      performance, visual memory, and learning) were examined in a group of 32 adults
      who had suffered mild to moderate head injury. Patients reported their symptoms
      with a four-point rating scale. Neurobehavioural functioning was assessed using
      computerized tests. Memory difficulties were the problems most frequently
      experienced by the patients and most closely associated with performance
      deficits.

PMID- 8260953
TI  - A comparison of the Glasgow Coma Scale and the Swedish Reaction Level Scale.
AB  - The Glasgow Coma Scale (GCS) and the Swedish Reaction Level Scale (RLS85), two
      level-of-consciousness scales used in the assessment of patients with head
      injury, were compared in a prospective study of 239 patients admitted to a
      regional head injury unit over a 4-month period. Assessments were made by nine
      staff members ranging from house officer to registrar, after briefing about the
      two scales. Data were also collected on age, nature of injuries, surgical
      treatment, and condition at discharge or transfer using the Glasgow Outcome
      Scale. Both the GCS and the RLS85 reliably identified comatose patients and those
      with minor head injury, but were much less effective in defining the response
      level in patients considered to have a moderate head injury. Only 41% of the
      patients allocated to a moderate-head-injury category by the GCS and the RLS85
      were common to both groups. Where a mismatch occurred, neither scale allocated
      patients to a 'better' or 'worse' category more frequently than the other.
      Assessment of patients' conscious levels using the GCS was difficult in only two
      cases. One patient had facial injuries, and the other was intubated. The RLS85
      was reported by all users to be simpler to use than the GCS, but the latter is
      much more widespread in use. Both scales function well in cases of severe and
      minor head injury, but have weaknesses when defining moderate head injury. Level
      of-consciousness scales are only an aid to assessment and the final choice
      between the two scales must remain a matter of personal or departmental
      preference.

PMID- 8260954
TI  - Incidence and correlates of depersonalization following head trauma.
AB  - Using the criteria of the Structured Clinical Interview for DSM-III-R
      Dissociative Disorders (SCID-D), we assessed the incidence of feelings of
      unreality among a sample of 70 persons who had sustained head injuries. Among
      those whose head trauma could be classified as mild, more than 60% complained of
      a depersonalization syndrome. Among those with a significant period of
      unconsciousness, only 11% had similar complaints. There was a high comorbidity
      with post-traumatic stress disorder and vertigo. Feelings of unreality were not
      associated with cognitive impairment or elevated personality test scores, nor
      were there significant relationships with gender or involvement in litigation. A
      conservative estimate of incidence of depersonalization among persons with minor
      head trauma is 13%, while, at the upper end, as many as 67% of persons who
      sustain mild head injury may experience feelings of unreality.

PMID- 8260955
TI  - Behavioural psychotherapy of the frontal-lobe-injured patient in an outpatient
      setting.
AB  - We present two cases of outpatient behavioural psychotherapy of frontal-lobe
      brain-injured adults. Unlike inpatient treatment of severely frontal-injured
      patients in which the hospital setting acts on the patient to modify behaviour,
      outpatient treatment teaches the self-motivated individual to use the structure
      and directiveness of behavioural psychotherapy to overcome his or her
      neuropsychological deficits. The literature describes two types of frontal
      syndromes: disinhibition and adynamia. Treatment of both types of syndromes is
      illustrated using case presentations. The therapeutic interventions for both
      syndromes are designed to exaggerate the link between stimulus and response to
      counter impaired processing of feedback. A six-stage behavioural psychotherapy
      model of the frontal-injured patient is outlined.

PMID- 8260956
TI  - Neuropsychological rehabilitation: application of a modified multiple baseline
      design.
AB  - The treatment of brain impairment following traumatic injury has proliferated in
      the past few years. Because many proposed treatment methods have not yet been
      proven, an important aspect of each treatment attempt is the evaluation of
      possible gains derived as a result of treatment. A modified multiple baseline
      design has been suggested as a means of partialing out extraneous influences in
      the assessment of treatment effects. This paper presents data from the
      application of a modified multiple baseline design to the treatment of memory and
      abstraction deficits in a young man who had experienced a closed head injury.
      Both psychometric-nomothetic and idiographic data are presented and discussed.

PMID- 8260957
TI  - Psychosocial rehabilitation of cranial trauma and stroke patients.
AB  - This paper presents the results of a longitudinal psychosocial study of 22
      cranial trauma patients and 14 stroke patients from the time preceding injury
      (using retrospective data), through a 4-5 month intensive rehabilitation
      programme, to a follow-up 1 year after completion of the programme. Although the
      two groups of patients differed on several demographic and medical
      characteristics, essentially similar patterns for psychosocial decline following
      injury and improvement following rehabilitation could be observed. For both
      groups, the proportion in marital or cohabitational relationships returned to pre
      injury levels, and for both groups the proportion requiring assistance in their
      living situation declined following rehabilitation, as did use of the health
      services. Virtually all patients in both groups had been in employment or
      undergoing education at the time of the injury, and although this percentage
      declined in practice to a small minority of both groups post-injury, there was a
      significant increase in the proportions working or in education following the
      rehabilitation programme. Similarly, the pattern of leisure-time activities in
      both groups declined post-injury and was restored following rehabilitation. Since
      both groups entered the programme at over 2.5 years post-injury, these generally
      encouraging results seem less likely to reflect spontaneous recovery than a
      beneficial effect of the programme itself.

PMID- 8260958
TI  - Traumatic brain injury: affecting family recovery.
AB  - Ongoing interest in how families adjust to traumatic events has encouraged much
      research, with varying results. Viewing the family process of adjustment from a
      systems perspective provides a workable model. The current article explores basic
      system tenets and provides data on varying adjustment issues for families.
      Results are consistent with current research trends and family data.

PMID- 8260959
TI  - Spontaneous thrombosis of a traumatic cavernous sinus fistula.
AB  - Post-traumatic thrombosis of cavernous sinus and orbital veins has been reported
      in conjunction with carotid-cavernous sinus fistula (CCSF). CCSF are abnormal
      communications between the carotid artery and the cavernous sinus. Spontaneous
      thrombosis of a CCSF is a rare event mainly seen in the indirect (dural) type of
      fistula. We report on a patient with a possible post-traumatic CSSF which
      underwent partial spontaneous thrombosis and presented with an extreme degree of
      proptosis.

PMID- 8260960
TI  - Diagnosis and molecular epidemiology of the African horse sickness virus by the
      polymerase chain reaction and restriction patterns.
AB  - African horse sickness is a viral disease caused by an orbivirus belonging to the
      Reoviridae family. This paper describes a polymerase chain reaction (PCR) for
      amplifying segments 7, which encode for VP 7, a protein common to the 9 known
      serotypes of this virus. A reverse transcription step is necessary before
      amplification. No amplified product could be observed in cell cultures infected
      with other equine viruses. The amplified DNAs were digested to completion by 8
      different restriction enzymes. The restriction fragment length polymorphisms
      allowed the differentiation of the group of serotypes AHSV-1, 3, 6, 8 and the
      viruses AHSV-2, AHSV-4, AHSV-5, AHSV-7 and AHSV-9. Differences could also be
      described between vaccinal strains of the same serotype produced in cell cultures
      or in brains of suckling mice.

PMID- 8260961
TI  - [Relationship between genetic markers and serum enzymatic activity in fighting
      bulls].
AB  - The relationships between 41 genetic markers (blood groups and biochemical
      polymorphisms), 3 environmental factors (season, management before the Lidia
      ("encierro"), punishment suffered), body constitution, and pedigree on the one
      hand, and the activity of muscular enzymes in serum, creatine kinase (CK),
      lactate dehydrogenase (LDH), aspartate transaminase (AST)) on the other, were
      analyzed in 179 fighting bulls. The C system of cattle blood groups and the
      "encierro" were significantly related to the activity of the muscular enzymes of
      the studied animals. The fighting bulls with the W1 and C1 antigens had a higher
      CK and LDH activity respectively, whereas the fighting bulls with the X1 antigen
      as well as those that participate in the "encierro" had a lower AST activity.
      This results could suggest a lesser degree of muscular injury during the Lidia in
      animals with X1 antigen, in those that participate in the "encierro", and in
      those without W1 and C1 antigens.

PMID- 8260962
TI  - [Eimeria tenella and Eimeria acervulina: an antigenic stimulation in vitro of
      cells from immune chickens induced by adoptive transfer of protection against
      avian coccidiosis].
AB  - The transfer of 5 x 10(7) or 10(8) spleen cells from E tenella-infected chickens
      to virgin animals after 12-20-h in vitro stimulation with whole sporozoite
      homogenates confers significant protection to recipients. The oocyst contents of
      ceca on d 7 post-infection with 20,000 E tenella oocysts were (1.33 +/- 1.10) x
      10(6) in chickens which received 5 x 10(7) immune cells after 20-h in vitro
      stimulation and (4.64 +/- 2.85) x 10(6) in chickens receiving 5 x 10(7)
      stimulated cells from normal chickens (85% protection). Adoptive transfer by
      spleen cells revealed an asymmetric cross-protection between E tenella and E
      acervulina. Spleen cells from E tenella immune chickens protected only against a
      subsequent infection with the same parasite, while spleen cells from E acervulina
      immune chickens protected against infection with E acervulina (78%) but also
      against infection with E tenella (68% protection). The common antigen permits
      better stimulation, but common surface sporozoite antigens purified from E
      tenella sporozoites via anti-E acervulina biliary antibodies are capable of
      stimulating both types of cells without, however, changing their properties.

PMID- 8260963
TI  - Ivermectin in goat plasma and milk after subcutaneous injection.
AB  - The pharmacokinetics and mammary excretion of ivermectin were determined in goats
      following a single sc administration (0.2 mg/kg). Kinetic analysis of plasma and
      milk levels was performed using a 1-compartment model. The maximum plasma
      concentration of 6.12 ng/ml occurred at 2.85 d; the half-life of 4.03 d was
      similar to the value in sheep (3.68 d). Ivermectin was detected in the milk at
      the first sampling time and thereafter for at least 25 d. Comparison of the milk
      and plasma data shows the parallel disposition of the drug in milk and plasma
      with a milk-plasma concentration ratio of 1.08 +/- 0.23. In conclusion, the
      persistence of the drug in plasma is reflected in the duration of the presence of
      ivermectin in milk.

PMID- 8260964
TI  - Field-oriented trial of the Chinese Brucella suis strain 2 vaccine on sheep and
      goats in Libya.
AB  - The Chinese Brucella suis S2 vaccine was studied in a flock of sheep and goats in
      field conditions. The locally-produced vaccine was orally administered in the
      form of a drench to 446 ewes, 50 lambs and 20 adult goats. After vaccination,
      abortion and excretion of the vaccine strain in vaginal discharges or in milk did
      not occur. Serological tests became positive in 92% of animals at 4 wk post
      vaccination and declined to near nil after 1 yr. The protection conferred by the
      vaccine against a double virulent B melitensis conjunctival challenge which
      infected 10/10 control ewes was on average 53% in ewes (32/60) and 71% in goats
      (5/7). Abortion rates were respectively 100% (7/7) in control ewes versus 44%
      (25/57) and 28% (2/7) in vaccinated ewes and goats. The vaccine was thus found to
      be safe, antigenic and reasonably protective against the challenge dose used.

PMID- 8260965
TI  - Isospora sp from ducks. Infectivity for the goose, four anatids and the domestic
      fowl.
AB  - A coccidium was isolated from mule duck farms, the sporulated oocysts of which
      most closely resemble that of Isospora anseris, a goose coccidium. By
      experimental infection, these oocysts were proved to be able to develop in the
      goose and in several duck species, but unable to develop in the chicken. No
      pathogenicity was noted in any species.

PMID- 8260966
TI  - [Midterm toxicity of nitrates: experimental evaluation of the effects on
      reproductive functions in the female rabbit].
AB  - Chronic exposure to low levels of nitrate are associated with detrimental effects
      on reproduction in animals. In order to determine this relationship, an
      experiment was conducted: female rabbits were given nitrate doses of 0, 250 or
      500 mg/l in drinking water for several months. After 2 successive gestations, no
      detrimental effect was observed on fertility, litter size or weight at birth and
      weaning, or on plasma oestradiol and progesterone concentration. Hemoglobin level
      was slightly decreased in dams given 500 mg/l.

PMID- 8260967
TI  - Comparative review of third-generation progestins.

PMID- 8260968
TI  - Effects on blood lipid and androgen levels of two triphasic oral contraceptives.

PMID- 8260969
TI  - Clinical review of a monophasic oral contraceptive containing desogestrel and
      ethinyl estradiol.

PMID- 8260970
TI  - Metabolic effects and efficacy of a triphasic oral contraceptive
      (norgestimate/ethinyl estradiol).

PMID- 8260971
TI  - Norgestimate: overview of a monophasic formulation.

PMID- 8260972
TI  - Gestational diabetes: the reality.

PMID- 8260974
TI  - PC, IBM, Mac, DOS--making sense of the alphabet soup.

PMID- 8260973
TI  - Midwifery in the information age.

PMID- 8260975
TI  - Watery births.

PMID- 8260976
TI  - The clean, smart uniform.

PMID- 8260977
TI  - Childbearing and parenting with a disability or chronic illness.

PMID- 8260978
TI  - What was your longest labor? How did you handle it?

PMID- 8260979
TI  - Kahlua and milk.

PMID- 8260980
TI  - A window to Bali.

PMID- 8260981
TI  - Midwifery in Trinidad.

PMID- 8260982
TI  - Unlocking the door to healing.

PMID- 8260983
TI  - Children at birth.

PMID- 8260985
TI  - Reflections on siblings.

PMID- 8260984
TI  - Midwifery is on course.

PMID- 8260986
TI  - Weighted justice.

PMID- 8260987
TI  - Preparing siblings.

PMID- 8260988
TI  - Does the baby like spinach?

PMID- 8260989
TI  - When should a child attend a sibling's birth? A guideline for parents.

PMID- 8260990
TI  - A bird's-eye view.

PMID- 8260991
TI  - A family affair.

PMID- 8260992
TI  - Trouble in paradise.

PMID- 8260993
TI  - "Money matters".

PMID- 8260994
TI  - Sharing experiences.

PMID- 8260995
TI  - Addressing the issue of sexual abuse.

PMID- 8260996
TI  - Peripherally-inserted central catheters: challenges for hospital management.
AB  - The peripherally-inserted central catheter (PICC) is an established technology in
      home intravenous (IV) therapy and its use is increasing in hospital and home
      health settings. Institutions introducing PICCs as another form of IV therapy
      will realize cost savings. However, challenges may be encountered. Implementation
      and education programs for staff, patients, and home caregivers will maximize the
      benefits of PICC use.

PMID- 8260997
TI  - Alcoholism in the elderly: implications for hospital nurses.
AB  - Alcoholism is a major illness that threatens the independent living status in
      many older persons. Nurses can assist in assuring adequate health care for
      elderly individuals suffering from alcohol abuse by addressing the social,
      physical, and psychological needs of this age group.

PMID- 8260998
TI  - Managing dobutamine infusions.
AB  - Each year, over 400,000 new cases of congestive heart failure (CHF) are
      diagnosed. Dobutamine, a synthetic inotropic agent, is used to boost myocardial
      function. While in the past dobutamine has been administered to patients under
      close observation in critical-care units, this treatment is now considered safe
      and cost-effective for use with patients on general medical-surgical units and
      even in the home when strict monitoring guidelines are followed. In these
      settings, assessment protocols and schedules guide nursing practice. Assessment
      priorities and suggested parameters for their frequency provide guidelines for
      nursing management.

PMID- 8260999
TI  - Fighting the needlestick battle without needles.
AB  - Institutions may face heavy fines by 1997 for not providing employees with safe
      sharps devices to prevent the spread of bloodborne pathogens to health care
      workers. One hospital decided to eliminate IVPB needles, which are responsible
      for the majority of needlestick injuries nationwide. To achieve this goal,
      medical-surgical nurses evaluated safe IVPB systems and chose one that decreased
      their needlestick injury rate by 68.6%.

PMID- 8261000
TI  - A model approach for patient education.
AB  - Patient education is an essential component of nursing care. The ASSURE model, an
      acronym for Analyze learners, State objectives, Select media and materials,
      Utilize materials, Require learner performance, and Evaluate/revise the learning
      and teaching process, is presented to assist nurses in organizing the process of
      patient education.

PMID- 8261001
TI  - Whistle blowing: an act of advocacy.

PMID- 8261002
TI  - Challenge for the 90s: a safe and cost-effective sitter program.

PMID- 8261003
TI  - Are you responsible for nursing's image?

PMID- 8261004
TI  - The family and Medical Leave Act of 1993: what does it mean to you?

PMID- 8261005
TI  - Tamoxifen for breast cancer therapy: nursing implications.

PMID- 8261006
TI  - Evaluating research for use in practice.
AB  - Before using research in practice, nurses must adequately evaluate both the
      scientific merit of the research and its potential impact on practice. This
      column outlined some basic questions that nurses can ask when reading research
      for use in practice. Many references in the nursing literature may be helpful to
      nurses who want to increase their skill in evaluating research for use in their
      own practice settings (Alderman, 1985; Haller et al., 1979; Jacox & Prescott,
      1978; Stetler & Marram, 1976; Topham & DeSilva, 1988). Clinical nurses have
      tangible knowledge of their own practice settings. This knowledge makes them the
      ideal decision-makers in determining when research findings are suitable for
      their practice. They should continue to develop their skills in evaluating
      research and form networks with nurse researchers, nursing faculty, clinical
      nurse specialists, and others with advanced research preparation to assist them
      in evaluating research and to validate their own assessment of the research. This
      kind of collaboration will promote prudent use of research findings in nursing
      practice.

PMID- 8261007
TI  - [Endoscopic techniques in the treatment of sterility related to micro-polycystic
      ovary syndrome].

PMID- 8261008
TI  - [Medical management of chronic Chlamydia trachomatis salpingitis resistant to
      usual antibiotics. Use of ofloxacin alone or combined with other anti-chlamydia
      antibiotics].

PMID- 8261009
TI  - [Hysterography: a possible come back?].

PMID- 8261010
TI  - [Fertility and environment: a new challenge].
AB  - Over the last thirty years the method for both investigating and treating
      fertility have become more sophisticated and powerful. At the same time, the risk
      factors for infertility have increased substantially, particularly those
      resulting from the environment. Spermatogenesis can be considered to be a marker
      for public health as the consequences of exposure to various factors can be
      determined objectively. The increase in the number of, and exposure to physical
      (ionising radiation, heat) and chemical (insecticides, pesticides, antimitotic
      agents) pose significant problems for human fertility. These issues need to be
      addressed by both epidemiologists and clinicians.

PMID- 8261011
TI  - [Influence of nitrates on reproduction in domestic mammals].
AB  - Nitrates and nitrites ingestion has been linked to adverse effects on
      reproductive efficiency, on the one hand by abortion in acute or subacute
      toxicity, on the other hand by impairment of fertility in chronic exposition.
      However, experimental studies show heterogeneous results and proposed mechanisms
      are still hypothetic. Experimental studies realised in rabbit in National
      Veterinary School of Nantes are presented. No detrimental effect on reproduction
      performances was seen in female rabbits given nitrate in the drinking water at
      levels of 250 or 500 mg/l during 22 weeks, but a decrease in retinol
      concentration in the liver of young rabbits born of exposed mother, and drinking
      themselves water with nitrate during 5 weeks, was observed.

PMID- 8261012
TI  - [Work and sterility. State of epidemiological research].
AB  - Among the factors of man or woman sterility some of them may be due to
      occupation. The identification of these factors may be performed through
      epidemiological studies; the fertility indices taken into account and the
      epidemiological strategies used are briefly described. As examples the results of
      studies on man hypofertility induced by dibromochloropropane and ionising
      radiations are presented.

PMID- 8261013
TI  - [Drug surveillance and reproduction in domestic animals].
AB  - Adverse effects of veterinary drugs, on the reproductive functions of domestic
      animals, represent an important aspect of veterinary pharmaco-vigilance. The data
      presented here are coming from the cases recorded by the National Centre of
      Veterinary Toxicological Informations or from published cases. The substances
      taken in account are mainly currently used drugs (antimicrobials, anti
      parasitic...) either of specific veterinary use, either used in both human and
      veterinary medicine.

PMID- 8261014
TI  - [Drug surveillance and reproduction: the bad example of distilbene].
AB  - In the 1940's, diethylstilboestrol (DES) is one of the first hormonal
      therapeutics which was prescribed to many pregnant women by a lot of
      gynecologists. Until 1970, the indications of this therapy was enlarged, before
      carcinologic and reproductive consequences leaded to forbid obstetrical
      indications of DES (in France, in 1977 only). In France, 80,000 girls and 80,000
      boys are suspected to have been exposed. As far as girls are concerned, the
      studies estimate between 23% and 36% the rate of infertility. These studies show
      also an increased incidence of ectopic pregnancy, spontaneous abortions, and
      premature delivery. The association between various factors of infertility, and
      typical uterine abnormalities leads to specific therapeutical indications, mostly
      in assisted procreations. The history of DES points out prescriptions of a
      therapeutic without proofs of its efficiency, the silence of pharmaceutical
      laboratories which did not take into consideration Dieckman's evaluation, and the
      difficulties for physicians in affording information. Nevertheless, the last
      patients exposed will be 40 years old in 2016 in France. The other hormonal
      therapeutics which were discovered gave in turn rise hope for enhancing the
      fertility and providing from miscarriage. Over the examples such as DES are not
      still resolved questions that patients and physicians ask concerning the lack of
      adverse effects of a therapy on the foetus, when its clinical efficiency on the
      pregnancy is supposed to be proved.

PMID- 8261015
TI  - [Influence of somatotropin treatment on the reproduction function in the dairy
      cow].
AB  - Currently somatotropin in being developed for use in several animal species,
      primarily as a productivity enhancer. The objective of this paper was to review
      direct and indirect effects of somatotropin supplementation on reproduction
      particularly in the dairy cow. There is substantial evidence that somatotropin
      plays an important role in the normal ovarian function. This effect is probably
      mediated via IGF-I. Existing literature indicates that higher milk yields are
      antagonistic to reproductive performance and require enhanced nutrition and
      reproductive management. Similarly, studies indicate that reproductive
      performance may be impaired in diary cattle supplemented with somatotropin.
      Effects of somatotropin treatment on reproductive performance may depend on the
      dose and the stage of lactation. Low doses of somatotropin in early lactation may
      improve reproductive function.

PMID- 8261016
TI  - [The use of growth hormone (hGH) in ovulation induction in women].
AB  - Number of in vitro experiments have shown increasing evidence for local ovarian
      actions of GH by demonstrating: the presence of receptors for GH in human
      granulosa cells; the ability of GH to enhance estradiol (E2) production by human
      granulosa cells withdrawn in late follicular phase; the increasing effect of GH
      on progesterone (P) biosynthesis by human luteal cells. Moreover, GH being the
      main regulator of IGF-I plasma levels, its indirect effect by means of hepatic
      and/or ovarian IGF-I production remains possible. Few patients have been included
      in randomized studies using hGH with gonadotropins for induction of ovulation and
      their selection criteria were heterogeneous so that no definitive conclusion can
      be drawn about the beneficial effect of GH in facilitating ovulation. The
      reduction both in duration of stimulation and in the requirement for menopausal
      gonadotropins found in some studies have been challenged by others. The
      recombinant human growth hormone (hGH) is able to modify the game of intraovarian
      regulators and may affects ovocyte and embryo. Such a potential impact cannot be
      occulted, justifying to develop larger in vivo animal experimentation before new
      further clinical studies.

PMID- 8261017
TI  - Effects of chronic captopril treatment on the electrical-microstimulation-induced
      blood pressure changes and electrophysiological properties of cardiovascular
      neurons in the rostral ventrolateral medulla of the spontaneously hypertensive
      rat.
AB  - The effects of chronic treatment with captopril, an angiotensin-converting enzyme
      inhibitor, on various properties of the rostral ventrolateral medulla (RVL) were
      studied in spontaneous hypertensive rats (SHR) given captopril (orally at a dose
      of 30 mg/kg) or vehicle from the age of 4-5 weeks to 19-20 weeks. In SHR, such a
      treatment with captopril resulted in an arterial blood pressure similar to that
      of normotensive Wistar Kyoto rats (WKY). Upon electrical microstimulation of the
      RVL, the minimal threshold current required to elicit a pressor response in
      captopril-treated SHR was significantly higher than that observed in SHR.
      Furthermore, analysis of the discharge pattern of RVL spinal projecting
      cardiovascular neurons showed a significant difference between captopril-treated
      and untreated SHR with respect to the proportion of double discharge units and
      the regularity of single discharge units. These properties of the RVL in
      captopril-treated SHR were, however, similar to those of WKY. Upon withdrawal of
      electrical microstimulation, the secondary sustained pressor response
      characteristic of SHR, but not of WKY, persisted in captopril-treated SHR at a
      smaller magnitude and a shorter duration. These results indicate that the
      normalization of arterial blood pressure in SHR upon chronic oral treatment with
      angiotensin-converting enzyme inhibitor is associated with changes in properties
      of RVL cardiovascular neurons towards those of WKY. This suggests that brain
      angiotensin and RVL cardiovascular neurons play interactive roles in the
      development of hypertension in SHR.

PMID- 8261018
TI  - Neuronal communication.
AB  - Since the initial description of simple chemical transmission systems involving
      one neurotransmitter, its respective receptor and second messenger, there has
      been an explosive growth in our understanding of the components and complexity of
      signal transduction systems involved in neuronal communication. Why did neurons
      develop such a complex signaling system, including coreleased neuromessengers,
      multiple receptor subtypes and interconnected transduction mechanisms? How is the
      specificity of a message encoded into a single neuromessenger maintained when the
      transduction pathways are shared by so many other molecules? How does a cell
      discriminate between the message carried by the same molecule conveying short
      term responses, endocrine messages, or signals for growth and differentiation? In
      the following article, the author tries to address these questions by providing a
      framework for cell-to-cell communication based on basic principle of information
      theory. It is suggested that many of the observed mechanisms of electrical and
      chemical transmission are a consequence of evolutionary strategies to develop
      efficient encoding and rapid, error-free transmission of information between
      cells.

PMID- 8261019
TI  - Localization of prostaglandin G/H synthase gene expression in rat brain by in
      situ hybridization.
AB  - Prostaglandin G/H synthase (PGH synthase; EC 1.14.99.1, cyclooxygenase) is a key
      enzyme in prostanoid biosynthesis. The cellular sites for PGH synthase gene
      expression have not been identified in any tissue. We have mapped the expression
      of PGH synthase in rat brain by in situ hybridization and have found large
      quantities of PGH synthase mRNA in the granular cell layer of the cerebellum,
      pyramidal layer of the hippocampus and granular cells of the dentate gyrus,
      moderate levels in pyramidal cells of the piriform cortex, cellular layers of the
      cerebral cortex, central nucleus of the amygdala, paraventricular, supraoptic and
      suprachiasmatic nuclei and cells of pituitary body, and low levels in most other
      regions of the rat brain. These results may provide a basis for an understanding
      of possible roles of PGH synthase in the central nervous system of adult rats.

PMID- 8261020
TI  - Protein kinase C as a multi-targeted feedback inhibitor regulating the Ca2+
      responses to chemotactic peptide stimulation in the murine macrophage cell line
      PU5-1.8.
AB  - The role of protein kinase C (PKC) in the signal transduction process when
      macrophage cells were stimulated by the chemotactic peptide formyl-methionyl
      leucyl-phenylalanine (fMLP) was investigated in the cell line PU5-1.8. Addition
      of fMLP to PU5-1.8 cells induced a rapid generation of inositol trisphosphate and
      a translocation of PKC. Concomitantly there was an influx of Ca2+ followed by its
      expulsion. PKC was likely involved in Ca2+ extrusion as short-term pretreatment
      of cells with phorbol 12-myristate 13-acetate (PMA) enhanced the removal of
      preloaded 45Ca2+ but had no significant effect on fMLP-stimulated 45Ca2+ influx.
      Depletion of cellular PKC activity through down-regulation or exposure of cells
      to PKC inhibitors also blocked the fMLP-stimulated 45Ca2+ efflux. Further
      experiments using PMA revealed that PKC also decreased vesicular Ca2+ and
      stimulated the catabolism of inositol 1,4,5-trisphosphate. These results lend
      support to the notion that PKC serves as a negative feedback modulator in Ca2+
      signalling and further suggest that it operates at several target sites.

PMID- 8261021
TI  - Cross-correlation study of synaptic input distribution inside the buccal ganglion
      of a gastropod mollusk.
AB  - In isolated 'nonperturbed' neural preparations of the gastropod mollusk Aplysia,
      synaptic inputs of undetermined origin ('spontaneous' synaptic activity) converge
      upon the buccal ganglion neurones. Activity simultaneously recorded from two
      neurones may include synchronous postsynaptic potentials (PSPs), due to firing of
      shared presynaptic cells. The distribution of spontaneous input to buccal
      neurones of known types (A, B, D, L and s cells) was quantitatively examined by
      cross-correlating intracellular recordings obtained from cells belonging to the
      same (homonomous) or different (heteronomous) type. Homonomous pairs of B or D
      motoneurones shared much of their input in all examined cases, compared to 50%
      cases for L neurones. Shared input appeared capable of facilitating synchronous
      firing in B and L cells, and of driving D cells in various phase relationships.
      Heteronomous pairs showed a high proportion of shared synaptic input when
      composed by A, B, D and s neurones, but no clear correlation was observed when
      pairing any of those four cell types with an L neurone. Shared synaptic input
      outlined therefore two buccal neuronal subsystems, internally coordinated and
      well separate from each other. The first one includes the A, B, D and s neurones,
      the second one, which is less compact, the L neurones. This agrees with an
      involvement of the first in patterned motor output production and of the second
      in coordination and control functions.

PMID- 8261022
TI  - The ratio of diffuse to mature beta/A4 deposits in Alzheimer's disease varies in
      cases with and without pronounced congophilic angiopathy.
AB  - The density of diffuse, primitive, classic and compact beta/A4 deposits was
      estimated in the cortex and hippocampus in Alzheimer's disease (AD) cases with
      and without pronounced congophilic angiopathy (CA). The total density of beta/A4
      deposits in a given brain region was similar in cases with and without CA.
      Significantly fewer diffuse deposits and more primitive/classic deposits were
      found in the cases with CA. The densities of the primitive, classic and compact
      deposits were positively correlated in the cases without CA. However, no
      correlations were observed between the density of the mature subtypes and the
      diffuse deposits in these cases. In the cases with CA, the density of the
      primitive deposits was positively correlated with the diffuse but not with the
      classic deposits. The data suggest that the mature beta/A4 deposits are derived
      from the diffuse deposits and that the presence of pronounced CA enhances their
      formation.

PMID- 8261023
TI  - Phosphorylation of tau by cyclic-AMP-dependent protein kinase.
AB  - Alzheimer's disease paired helical filaments contain abnormally phosphorylated
      tau (PHF-tau) which has reduced electrophoretic mobility on sodium dodecyl
      sulphate polyacrylamide electrophoresis. We have investigated the effects of
      cyclic-AMP-dependent protein kinase (PKA) on recombinant human tau isoforms and
      two recombinant tau fragments. PKA phosphorylated tau and reduced its
      electrophoretic mobility, phosphorylation towards the C-terminus of tau having a
      major influence on this property. Substitution of serine396 (phosphorylated in
      PHF-tau) or serine416 (phosphorylated by calcium/calmodulin kinase II) by alanine
      demonstrated that these are not major sites for PKA phosphorylation. Although the
      phosphorylated forms of tau generated by PKA are not identical to those of PHF
      tau, PKA may be involved in the generation of PHF-tau in Alzheimer's disease via
      phosphorylation of additional, as yet unidentified, sites on tau.

PMID- 8261024
TI  - Induction of memory and cortical cholinergic neurochemical recovery with combine
      fetal transplantation and GM1 treatments in rats with lesions of the NBM.
AB  - Sixty-four Sprague-Dawley rats received ibotenic-acid-induced unilateral nucleus
      basalis of Meynert (nbM) lesions; 10 additional animals served as sham controls.
      Eight to ten days later, subjects with lesions received either fetal cholinergic
      transplants implanted within the ipsilateral (relative to the lesion) frontal
      cortex or control transplant surgeries. Lesioned animals with and without
      transplants were then treated with GM1 (20 mg/kg, i.p.) for either 0, 1 or 10
      days and were then trained and tested for 72-hour retention of passive avoidance.
      Results indicated that the lesion produced a significant impairment on this task.
      Transplant therapy combined with GM1 for 10 days yielded a significant reversal
      of this deficit. GM1 injections continued once per week for 4 weeks for half the
      lesioned animals in the transplant and no-transplant 10-day conditions. During a
      6-month period, all subjects were assessed on two additional memory tasks
      (complex spatial discrimination and delayed spatial alternation). In general,
      there was no indication of a lesion, transplant, GM1, or transplant X GM1 effect
      on these tasks. Approximately 7.5 months after transplants, subjects were
      sacrificed and their frontal cortices examined for choline acetyltransferase
      (CAT) and acetylcholinesterase (AChE) activity. Only lesioned subjects with
      transplants which were given sustained GM1 treatment (i.e., 10 days plus weekly
      injections for 4 weeks) showed significant attenuations of lesion-induced CAT and
      AChE depletions. These data suggest that a combined treatment strategy of fetal
      transplant plus GM1 is capable of reversing nbM lesion-induced memory and
      neurochemical deficits in an animal model of the cholinergic deficits in
      Alzheimer's disease.

PMID- 8261025
TI  - Variation in psychiatric and behavioural symptoms at different stages of
      dementia: data from physicians' examinations and informants' reports.
AB  - An investigation was carried out of psychiatric and behavioural symptoms in non
      demented and demented subjects derived from a population study of the very
      elderly. Information on psychiatric and behavioural symptoms came from two
      independent sources: a physician's examination and an interview with an
      informant. The symptoms were grouped into clusters using principal-components
      analysis. Little agreement was found between the two sources of information on
      symptoms of anxiety, depression and psychosis. However, there was agreement about
      an increase in inactivity symptoms as the severity of dementia increased.

PMID- 8261026
TI  - Influence of feelings of burden on the caregiver's perception of the patient's
      functional status.
AB  - We studied the correlation between the caregiver's feelings of burden and the
      cognitive, behavioral and functional impairment of demented patients. We
      attempted to show the influence of caregiver's feelings of burden on their
      perception of the patients' functional status and to establish the predictors of
      feelings of burden. Twenty-five probable Alzheimer disease patients (NINCDS-ADRDA
      criteria) were assessed on cognitive measures and functional status (DAFS). The
      caregiver's index of burden (CIB), obtained from an adapted version of the Zarit
      Burden Interview, was correlated with the caregiver's report on the patient's
      instrumental activities of daily living (IADL) and physical self-maintenance
      functions (ADL); total and partial DAFS scores, and patient's cognitive and
      behavioral problems rated with the Functional Dementia Scale (FDS). The CIB
      correlated with the caregiver's report on the patient's behavioral disturbances
      (r = 0.71, p < 0.001) and physical self-maintenance activities (r = 0.62, p <
      0.001), but not with cognitive impairment, IADL and the DAFS. The patients showed
      better functional performance in the direct assessment than in that reported by
      their caregivers (mainly in shopping, feeding, dressing, and ambulation). Thus,
      burden may foster a growing intolerance of the caregiver, inducing an
      underestimation of the patient's actual functional competence. The caregiver's
      report on the patient's behavioral problems was the best predictor of feelings of
      burden (P = 19,9, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261027
TI  - A comparison of cognitive impairments in dementia of the Alzheimer type and
      depression in the elderly.
AB  - General cognitive function and specific language and memory processing abilities
      were compared in dementia of the Alzheimer type (DAT), depressed and normal
      control subjects. Several tests clearly differentiated between DAT and depressed
      subjects including a verbal fluency task, several components of a word memory
      test, an IQ deterioration index, and the Mini-Mental State Examination. The
      inability of DAT subjects to take advantage of semantic cues in both the verbal
      fluency and in the memory test contrasted with the performance of depressed and
      normal subjects, who were able to benefit from semantic cues. Depressed patients
      displayed deficits compared with normal controls on the more effortful verbal
      fluency task but not on the memory test. Tasks that are least effortful, rely on
      semantic associations, and require declarative memory are most likely to
      discriminate between DAT and depression.

PMID- 8261028
TI  - Research in pregnancy and mental illness: testing old wives' hypotheses.
AB  - Methodological challenges encountered in evaluating the relationships between
      life stress, mental illness and pregnancy outcome are identified and several
      studies on the relationships between pregnancy and childbirth and psychosocial
      factors, including life stresses, major psychiatric disorders, and puerperal
      depression, are reviewed. Certain methodological pitfalls are illustrated by
      showing how relationships between psychiatric diagnosis, severity of psychiatric
      symptomatology, life stresses, strains specific to the pregnancy, amount of
      intervention received and outcome of keeping or losing the infant have been
      explored. Five stages of research are identified and particular difficulties
      encountered at each stage are described with application to the authors'
      longitudinal study.

PMID- 8261029
TI  - Visual display units and pregnancy outcome: a prospective study.
AB  - This paper presents the results of a prospective study of the impact of work with
      visual display units (VDUs) and associated ergonomic and stress variables on
      pregnancy outcome and infertility. An apparent relationship between VDU use and
      pregnancy outcome in retrospective data probably reflected the operation of
      recall bias. Prospective data did not reveal any evidence for an adverse effect
      of VDUs on pregnancy in this sample, or any mechanism by which such an effect
      could occur. There was no evidence for any effect of VDU use on infertility.
      Implications for working women and future research are also presented.

PMID- 8261030
TI  - A simple strategy to detect significant premenstrual changes.
AB  - The prevalence of the ten most prominent premenstrual symptoms (top-ten) was
      calculated in Dutch women (n = 202), who considered themselves to suffer from
      complaints related to menstruation. Premenstrual syndrome was diagnosed where the
      scores of 5 or more of the top-ten symptoms showed an increase of at least 2
      points (on a visual analog scale rated from 1 to 10) from day 12 to day 26 during
      two consecutive cycles. This diagnosis was confirmed in almost all subjects using
      a 'gold standard' criterion of an increase of at least 30% in complaints from the
      follicular phase to the luteal phase. In contrast to the latter strategy the 'top
      ten' method successfully excluded women who felt free from premenstrual
      complaints. It is concluded that the 'top-ten' method is a simple and valid
      strategy to detect significant premenstrual changes.

PMID- 8261031
TI  - Premenstrual experiences: the four profiles and factorial patterns.
AB  - Premenstrual experiences were studied in 112 non-complaining women using the
      Premenstrual Assessment Forms I (for positive experiences), II (for distressing
      experiences) and the bi-directional Visual Analog Scale. Overall, 27% of women
      reported no or minimal changes, 20% reported predominantly negative experiences,
      and 18% predominantly positive feelings. However, the commonest experience was a
      mixed picture with coexisting positive and negative feelings in 35% of the
      subjects. Severe premenstrual changes were noted in only nine (8%) of the women.
      None had a late luteal phase dysphoric disorder. The 26 items of the Premenstrual
      Assessment Forms I and II were factor analyzed by the principal components method
      using a varimax rotation. Four factors were derived. Factor I had 12 items
      indicating negative experiences. Factor II had seven items indicating positive
      feelings. The other two factors have vegetative features (like sleep and bowel
      changes) and sexual feelings. The findings also indicated that research needs to
      be directed towards understanding the mixed group of symptoms rather than the
      excessive emphasis on negative feelings.

PMID- 8261032
TI  - Individual behaviour and tobacco consumption: a panel data approach.
AB  - This paper considers estimators of tobacco demand equations using Becker and
      Murphy's model of addiction with a complete panel of households for Spain. With
      these tools, we face two main problems: first, the endogeneity of past and future
      consumption and, second, the limited-dependent variable. To control these
      problems simultaneously is difficult and we proceed to confront them separately.
      We follow an instrumental variable approach (which also allows us to control for
      measurement errors in variables and non-independent effects) to tackle the first
      and we use a consistent within-group procedure to obtain the parameter vector of
      the structural form, once we have estimated T-Tobit models for the reduced form
      in order to deal with the limited-dependent variable problem.

PMID- 8261034
TI  - Health care expenditure and income in Europe.
AB  - In this work we have tried to analyse the variations in health care expenditure
      in all the countries of the European Community except Greece and Portugal. We
      have wanted to provide additional evidence on the empirical relationship between
      expenditure on health care and income. Our analysis, starting from the approach
      of Fuchs and Baumol, has been an extension of the traditional studies on health
      care international comparisons, in at least three directions: we have not imposed
      any restrictions on the price effects, we have analysed dynamic models instead of
      the cross-sectional analysis and we have used proper deflators. We have deflated
      health care expenditure in each country by means of its sectoral price index and
      by the purchasing parity power of its currency, to allow international
      comparisons. In the former case we express health care in terms of 'expenditure',
      in the latter we express health care in terms of 'weighted quantity'. Income
      elasticities, in the short and in the long-run, have been estimated using
      econometric methods that allow us to obtain simultaneously equilibrium long-run
      relationships, if any, and adjustment processes in the short-run. We have found
      cointegrating relationships and we have estimated consistent estimators of the
      elasticities. The estimated income elasticities are greater than one in all the
      models analysed.

PMID- 8261033
TI  - Econometric analyses of national health expenditures: can positive economics help
      to answer normative questions?
AB  - The size of national health care expenditure is an important research and policy
      issue. This paper reviews theoretical and empirical analyses of an implied
      optimal size for a health sector. Various economic theories are explicitly or
      implicitly invoked, but none is fully satisfactory. Theory provides, at best, a
      loose justification for empirical specifications of health sector behaviour.
      Nevertheless, this has a large and growing empirical research industry. The
      complexity of the issues provides an excuse for reliance on empirical analyses
      using ad hoc models. The paper analyses aggregate time-series data, using the
      cointegration approach, on health, health care expenditures and national income.
      Only one national model met both statistical criteria and showed a significant
      relationship: between potential life years lost and health care expenditure in
      the UK. The case for any general relationships remains unproven. There is no
      objective scientific method to determine optimal health expenditure, nor should
      we expect one. However, positive analyses can help with normative questions. A
      better understanding of health expenditure determination would arise from better
      specification of the relationships, perhaps by analysis at a lower level of
      aggregation.

PMID- 8261035
TI  - Income transfers and the labour market participation of disabled individuals in
      the UK.
AB  - Data from the OPCS Disability Survey are used to model the labour force
      participation of disabled individuals. The model is an endogenous switching
      regression and estimation is by the two stage probit procedure. The estimates are
      used to simulate the impact of Disability Working Allowance, introduced in April
      1992, on the participation rate of the disabled population.

PMID- 8261036
TI  - A cell based approach to modelling public expenditure.
AB  - The paper examines the use of a cell based model to analyse the effects of
      demographic change on the level and distribution of public expenditure. The
      nature and advantages of a cell based model for this purpose are described. The
      level and distribution of the key components of welfare state expenditure-
      health, education, social security--and of direct taxes, is examined for the base
      year of 1985. The net transfer of resources is compared to the distribution of
      income across cells. The effect of demographic change on the level and
      distribution of health and education expenditure is analysed. Issues in the
      further development of this approach are then reviewed.

PMID- 8261037
TI  - Financial incentives for physicians: the Quebec experience.
AB  - This paper presents an empirical investigation of physician labour supply, based
      on a two-stage budgeting model, drawing on an analogy with consumer theory.
      Physicians' trade-offs between income and leisure constitute the first stage of
      the decision-making process. In turn, choices are made in the second stage
      concerning the choice of particular activities (hospital versus office care, for
      example) or procedures (ordinary versus complete medical examinations), given the
      total medical care activity chosen in the first stage. The objective of the study
      is to identify physicians' responses to exogenous shocks in the remuneration
      system. The focus of analysis is shifted away from the identification of Supply
      Induced Demand (SID) to a more pragmatic analysis of some of the determinants of
      physicians' choices. The study uses monthly activity data on a panel of 677
      Quebec GPs between 1977 and 1983. Quantity adjustments and drifts to more complex
      (and therefore better paid) procedures are evidenced, mainly in response to a
      fifteen month tariff-freeze. Physicians' ability to control their own work loads
      is also documented, both in terms of timing and level of complexity, and
      expenditure caps (in the form of an individual ceiling on GPs' quarterly gross
      income) are found to be effective at curbing high activity rates.

PMID- 8261038
TI  - Capitation payments based on prior hospitalizations.
AB  - In many countries the concept of capitating health care insurers is receiving
      increasing attention. In a competitive environment, capitation should induce
      insurers to concentrate more on cost containment instead of indulging in risk
      selection. The necessary premium-replacing capitation payments should account for
      predictable variations in annual per-person health care expenditures as far as
      these are related to health status. Various studies have shown that crude
      capitation models based on e.g. age, sex and place of residence, do not reflect
      expected costs accurately. This implies inefficient pricing possibly leading to
      risk selection and windfall profits or losses for insurers, thereby undermining
      the objectives of a capitation system. Using Dutch micro data on some 200,000
      individuals, this article stimulates various alternative capitation models based
      on, among others, diagnostic information from previous hospitalizations. Results
      suggest that the problems of both risk selection and windfall profits/losses may
      be mitigated substantially by using this type of information together with data
      on prior costs. These results are not only relevant for situations where
      competing insurers are capitated, as intended in the Netherlands, but also when
      providers are capitated, as in the UK, or when HMOs are capitated, as in the US.

PMID- 8261039
TI  - The demand for health: an empirical reformulation of the Grossman model.
AB  - Previous tests of Grossman's model of the demand for health have been based on
      Grossman's own empirical formulation. This paper argues that this formulation
      fails to capture the dynamic character of the model. It proposes an alternative
      formulation, which appears to be more consistent with Grossman's theoretical
      model and which may also explain the apparent rejections of the model by the data
      in the author's earlier empirical work. The paper also presents some empirical
      results obtained using the new formulation, which are, on the whole, consistent
      with the predictions of Grossman's theoretical model.

PMID- 8261040
TI  - Equitable access to health care: methodological extensions to the analysis of
      physician utilization in Canada.
AB  - In this paper we analyse the distribution of family physician use in Canada to
      explore whether the stated goal of reasonable access to care has been achieved.
      We test hypotheses to see whether (a) variations in incidence and quantity of use
      are independent of need for care as proxied by self-assessed health status and
      (b) any observed relationship between variations in use and need is independent
      of other population characteristics. Previous research has conceptual,
      statistical and data limitations which bring into question the validity of the
      findings. These limitations are addressed by using more appropriate data, a
      conditional model for service utilization and correction for self-selectivity of
      users in the statistical analysis. Variations in need are identified as important
      and significant in explaining variations in both incidence and quantity of use
      with the estimated relationship between use and need being positive. Other
      population characteristics were found to be important and significant in
      explaining variations in use although household income is not among them. The
      relationship between use and need is associated with other variables including
      education, social support and region of residence. These findings suggest that
      analyses of utilization based on simple multivariate techniques and aggregate
      data can produce a picture of utilization that conceals important, policy
      relevant relationships while revealing other relationships that are essentially
      artifacts of inappropriate aggregation in ways which provide a false sense of
      achievement.

PMID- 8261041
TI  - Who updates the teachers?

PMID- 8261042
TI  - Casemix in the political blender.

PMID- 8261043
TI  - Tackling alcohol problems in a general hospital.

PMID- 8261044
TI  - Alcohol screening: one hospital's experience.

PMID- 8261045
TI  - Give voice to your thousand silent screams.

PMID- 8261046
TI  - Evaluation of new health technologies. Part 4 of health care economics.

PMID- 8261047
TI  - Nursing and the law. Witness to battery?

PMID- 8261048
TI  - Code of ethics for nurses in Australia.

PMID- 8261049
TI  - Wound care.

PMID- 8261050
TI  - Health insurance. Part 5 of health care economics.

PMID- 8261051
TI  - Nursing and the law. Discontinuing treatment: a landmark case.

PMID- 8261052
TI  - Doppler echocardiographic evaluation of diastolic ventricular function in
      coronary artery disease.

PMID- 8261053
TI  - Doppler stress echocardiography of the left and right ventricle: a new echo
      device to quantify left ventricular backward failure.
AB  - OBJECTIVES: A novel non-invasive procedure which evaluates left-right ventricular
      interaction is introduced. This procedure is suitable for the classification of
      congestive heart failure. METHODS: In 48 patients showing mild, moderate or
      advanced stage congestive heart failure (NYHA I-III) Doppler echocardiography was
      performed at rest, during and after submaximal bicycle exercise. Mitral (m) and
      tricuspid (t) filling parameters were determined: early diastolic (VEm, VEt) and
      atrial maximal velocities (VAm, VAt), the velocity integrals (Em, Et, Am, At) and
      the corresponding ratios (VE/VAm, VE/VAt, E/Am, E/At). Group 1 (n = 29) was
      composed of those patients presenting with a VE/VAm < 1 at rest. Four individuals
      (group 2) were found to have a VE/VAm ratio < 1 during exercise only. Six other
      patients showing a dilated left ventricle or an ejection fraction of less than
      40% produced false negative results in left ventricular Doppler examination
      (VE/VAm > 1) at rest and during exercise (group 3). In 9 cases (group 4) systolic
      function, size and Doppler echocardiographic parameters of the left ventricle
      were proven to be normal. RESULTS: The VE/VAt-ratio decreased notably during
      exercise (p < 0.05) but increased again after exercise in group 3. In the groups
      1 and 2 similar changes occurred as well, however not to a significant degree. In
      group 4, exercise VE/VAt ratio did not differ from values seen at rest or during
      recovery (variability 4%). CONCLUSION: The results of this study indicate, that
      high sensitivity towards left ventricular backward failure can be achieved for
      Doppler stress echocardiography by extending the examination to right-sided
      diastolic parameters.

PMID- 8261054
TI  - Recovery from staphylococcal septicaemia in neutropenic patients without removal
      of the previously inserted central venous catheter.
AB  - OBJECTIVES: An open clinical study was conducted in the haematological department
      of an intensive care unit to investigate cure of staphylococcal septicaemia in
      neutropenic central venous catheter carriers without removal of the line.
      METHODS: Thirteen neutropenic patients with a central venous catheter were
      investigated. These patients were under treatment for haematological malignancies
      and had at least 2 blood cultures positive for Staphylococcus aureus or coagulase
      negative staphylococcus. Antibiotherapy including vancomycin was given through
      the catheter. Each case was re-evaluated on day 3 of treatment. The catheter was
      removed if blood cultures remained positive or if clinical signs of bloodstream
      infection persisted or worsened. RESULTS: Clinical recovery was obtained in ten
      patients and bacterial eradication in twelve. Three patients died from septic
      shock: two deaths were not related to staphylococcal septicaemia; one death was
      due to a staphylococcal septic shock which occurred within a few hours of
      admission, despite of prompt removal of the central venous catheter. CONCLUSIONS:
      With appropriate antibiotherapy, leaving the central venous catheter in place
      would appear possible in cases of staphylococcal septicaemia. Response to
      treatment, however, must be carefully monitored.

PMID- 8261055
TI  - Rapid identification of mycobacteria from culture using acridinium-ester-labelled
      DNA probes.
AB  - OBJECTIVES: Our study used newly developed acridinium-ester-labelled DNA (AE-DNA)
      probes on 183 mycobacterial isolates, performing the tests on 12B Bactec vials
      and Loewenstein-Jensen (LJ) slants. METHODS: The probe results were verified
      using the conventional method as a reference. RESULTS: The probe for M.
      tuberculosis complex correctly identified 131 of 133 M. tuberculosis isolates,
      with two false negatives and no false positives, for a sensitivity of 98.5% and a
      specificity of 100%. The M. gordonae probe correctly identified 27 out of 27 M.
      gordonae isolates, with no false negatives and one false positive, for a
      sensitivity of 100% and a specificity of 90.9%. One hundred sixty-eight of the
      183 isolates were screened in accordance with an algorithm, designed primarily
      for the rapid detection and identification of M. tuberculosis. CONCLUSION: The
      use of the algorithm considerably reduced detection time: M. tuberculosis strains
      were identified within 16.2 +/- 2.3 days, while identification by conventional
      method required 35.7 +/- 5.5 days. Probe testing resulted in a cost increase of
      67.8%.

PMID- 8261056
TI  - Accelerated nodulosis and systemic manifestations during methotrexate therapy for
      rheumatoid arthritis.
AB  - OBJECTIVES: Methotrexate is successfully used in the treatment of arthritis but
      little is known about its effects on extra-articular manifestations of rheumatoid
      arthritis. We focused this work on the incidence and clinical course of extra
      articular manifestations during long-term treatment with methotrexate. METHODS:
      The effect of methotrexate on extra-articular manifestations was investigated in
      176 patients with rheumatoid arthritis who had obtained, in a prospective study,
      a good clinical response to methotrexate (10 mg/week) taken for 33 months (range
      4-68). RESULTS: Before taking methotrexate, 44 patients (25.1%) had extra
      articular manifestations: nodules (n = 40) and vasculitis (n = 9). With
      methotrexate, nodulosis and vasculitis were stable in 31 cases, improved in 3 and
      worsened in 10 (23%). Among the 132 patients without extra-articular
      manifestations before methotrexate therapy, 15 (11%) developed accelerated
      nodulosis preferentially located on the fingers, 7 had a vasculitis and 3 a
      pericarditis during methotrexate therapy. Extra-articular manifestations occurred
      between 1 and 24 months of initiating methotrexate therapy. Rheumatoid factor was
      positive in 88% of the patients with extra-articular manifestations. No
      relationship was noted between extra-articular manifestations and HLA type or
      antinuclear antibodies. In 3 out of 4 patients who developed accelerated
      nodulosis while taking methotrexate, the addition of hydroxychloroquine (400
      mg/day) resulted in a significant reduction in the number and size of the nodules
      within 3 to 10 months after starting combined therapy. CONCLUSION: These data
      suggest that methotrexate is not effective in the treatment of extra-articular
      manifestations in rheumatoid arthritis and that nodulosis may occur in about 11%
      of patients taking methotrexate therapy for rheumatoid arthritis. The combination
      of hydroxychloroquine and methotrexate may have a beneficial effect on nodulosis
      that needs to be evaluated.

PMID- 8261057
TI  - Ultrasonic assessment of bone: a review.
AB  - In the last 25 years several non-invasive techniques based on the attenuation of
      ionizing radiation have been developed to quantify bone mineral density in the
      axial and peripheral skeleton. The use of ultrasounds is another technique which
      has recently been developed to provide information on the architecture and
      elasticity of bone. The basic principle of ultrasound measurements is that the
      speed (SOS = speed of sound) at which ultrasounds propagate in the bone, or the
      extent of their attenuation (BUA = broad-band ultrasound attenuation) through the
      bone is determined by bone density and by certain physical properties which are
      intimately correlated with bone strength. Theoretically, ultrasound bone
      measurements should provide more information about bone fragility and structure
      than densitometric techniques. As a result of preliminary studies, several
      ultrasound devices have been developed by manufacturers. Most of them measure the
      os calcis which consists almost exclusively of trabecular bone. Measurement
      precision varies with the instrument used and the site of measurement. The in
      vitro and in vivo precision for SOS and for BUA are reported in this review. The
      correlations between ultrasound and bone mineral density measurement suggest that
      these techniques measure different entities. A significant difference is
      constantly found between normal and osteoporotic women. Transversal studies have
      shown a negative correlation between ultrasound measurements and age. Age-related
      variations are much more significant with BUA than with SOS. Several studies
      suggest the potential of ultrasound measurements to assess the risk for
      individuals to develop osteoporosis and its usefulness in treatment follow-up.
      Further prospective studies are needed to better understand the effectiveness of
      ultrasounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261058
TI  - Asthma and neuropeptides.
AB  - Non-adrenergic non-cholinergic nerves, first described in the gut, were
      identified in the lung about twenty years ago. These fibers constitute in the
      airways an extensive network of nerve endings containing a great amount of
      neuropeptides which can influence bronchi smooth muscle tone and control airway
      calibre. These mediators can also modulate immune function and cellular responses
      characteristic of inflammation in the bronchi. It is obvious that they can play
      an important role in asthma, and it is likely that a better understanding of the
      mechanisms of action of these substances will lead to new treatments in asthma.

PMID- 8261060
TI  - Progression of multiple primary plasmacytomas under interferon-alpha therapy.

PMID- 8261059
TI  - Are total hip prostheses implanted with the use of methylmethacrylate
      biocompatible?
AB  - OBJECTIVES: The biocompatibility of total hip replacement prostheses and
      methylmethacrylate cement which is used for fixation of the prosthetic components
      has been subject to debate for three decades. METHODS: We have studied the host
      response to total hip replacement prostheses in a number of clinical and
      experimental investigations. RESULTS: Methylmethacrylate cement is
      immunologically relatively inert while it causes, in in vitro experiments and in
      vivo, a foreign body type of reaction. In cementless prostheses, the wear of
      polyethylene which is used for lining of the acetabular component causes a
      similar foreign body type of reaction. CONCLUSION: Ultimately, the total hip
      prosthesis cannot be made invisible to the host system. The host response can be
      controlled and reduced, but not eliminated by technical improvement and
      development of more biocompatible materials.

PMID- 8261061
TI  - Syndrome of inappropriate antidiuretic hormone secretion following cis
      dichlorodiammineplatinum II in a patient with laryngeal carcinoma.

PMID- 8261062
TI  - A familial case of spondylometaphyseal dysplasia and a review of the literature.

PMID- 8261063
TI  - Hepatotoxicity due to verapamil hydrochloride.

PMID- 8261064
TI  - Cholesterol emboli-induced renal failure following cardiac angiography.

PMID- 8261065
TI  - Circadian rhythmicity in the onset of fatal pulmonary embolism in hospitalized
      subjects.

PMID- 8261066
TI  - Cytomegalovirus infection in previously healthy adults.

PMID- 8261067
TI  - On the necessity of anticoagulant therapy during the initial phase of steroid
      treatment in giant cell arteritis.

PMID- 8261068
TI  - Parenteral risk factors for hepatitis C virus in alcoholics with chronic liver
      diseases.

PMID- 8261069
TI  - Hepatitis C virus infection in chronic hepatitis B virus carriers.

PMID- 8261070
TI  - The "endocrine" dysmetabolism of visceral obesity. Lessons from exercise
      research.

PMID- 8261072
TI  - Enterovirus infections in neonates. A retrospective study of 21 cases.
AB  - OBJECTIVES: The aim of this study was to define the major features of enterovirus
      infections in the neonatal period based on our own experience. METHODS:
      Epidemiology, clinical manifestations and laboratory investigations concerning 21
      neonates having experienced a Coxsackie B or an Echovirus infection between 1987
      and 1991, were retrospectively reviewed. Aetiological diagnosis was made by
      classical viral isolation and/or by evidencing Coxsackie B-specific IgM
      antibodies with an immunocapture enzyme immunoassay. RESULTS: In 13 neonates the
      infection occurred between June and September. The onset of clinical signs ranged
      from day 1 to day 25 after birth with two separate periods: before 7 days of age,
      suggesting a perinatal transmission of the virus, or beyond this date, more
      likely connected with a postnatal transmission. Clinical manifestations included
      hyperthermia, gastroenteritis, meningitis, encephalitis, pneumonia and
      myocarditis, with a diphasic pattern in 6 cases. Most of the neonates improved
      gradually and developed normally. The Coxsackie B-specific IgM assay was the most
      rapid method whereas viral isolation, even though it took more time, was the most
      sensitive technique to establish the aetiological diagnosis in neonates.
      CONCLUSIONS: Enterovirus infections in neonates are difficult to diagnose and to
      differentiate from bacterial infections. A viral-like illness in the environment
      of the neonate allows the clinician to anticipate the clinical signs and a
      possibly fatal disease. Identification of the causal virus should be performed by
      both viral isolation and search for specific IgM antibodies. Treatment and
      prophylaxis are so far disappointing.

PMID- 8261071
TI  - Age, sex, cigarette smoking and indices of free radical activity in healthy
      humans.
AB  - OBJECTIVES: To determine the effect of age, sex and smoking on free radical (FR)
      indices. There is currently considerable research interest into the role of FRs
      in the pathogenesis of many diseases and it is therefore important to identify
      factors in healthy subjects which influence the markers used to assess FR
      activity. METHODS: Blood samples were obtained from 123 healthy subjects whose
      age, sex and smoking habits were recorded. The following were measured on each
      sample: malondialdehyde (MDA) which is a product of FR mediated lipid
      peroxidation and the FR scavengers plasma thiols (PSH), red cell glutathione
      (GSH) and superoxide dismutase (SOD). RESULTS: Malondialdehyde levels were
      significantly increased in cigarette smokers (p < 0.02) but no significant age
      related increase in MDA was detected for the group as a whole. However, female
      smokers had the highest rate of MDA increase with age followed by male smokers
      and female non-smokers. MDA levels of male non-smokers were unaffected by age. A
      significant negative correlation was detected between PSH and age (p < 0.001).
      GSH was significantly higher in females (p < 0.05) and the red cell content of
      GSH and SOD were significantly inversely related (p < 0.01). CONCLUSION: This
      study of normal subjects describes an age related increase in malondialdehyde
      levels, the rate of which is influenced by sex and smoking status. In humans,
      plasma thiol levels decrease with increasing age, females have higher red cell
      glutathione and there is a significant inverse relationship between red blood
      cell superoxide dismutase and glutathione levels. Furthermore, cigarette smoking
      increases plasma malondialdehyde levels. With the considerable current interest
      in free radicals, it is important to identify factors which influence the indices
      used to assess free radical activity in disease states.

PMID- 8261073
TI  - The diabetic foot in Dutch hospitals: epidemiological features and clinical
      outcome.
AB  - OBJECTIVE: To assess the impact of the diabetic foot on the hospitalization of
      patients with diabetes mellitus in The Netherlands. METHODS: Data on
      hospitalizations of patients with diabetes mellitus for the years 1988 and 1989
      were obtained from the Dutch Information System on Hospital Care. Analysis of the
      data was performed if in the discharge summary a code number for chronic ulcer of
      the lower extremity, osteomyelitis or gangrene was reported. RESULTS: In 1988
      20.4% of all hospitalized diabetics were reported to have foot problems. The men
      age of the study population was 71.3 +/- 12.1 years for 1988 and 71.2 +/- 11.9
      for 1989. In patients who underwent (partial) limb amputation the M/F ratio was
      higher than in patients without amputation for all patient groups studied (p <
      0.001). In 1988, 3707 and in 1989, 3790 patients were hospitalized for diabetic
      foot problems. The cumulative costs were calculated to be 38,556,960 ECU for 1988
      and 37,720,020 ECU for 1989. The mean duration of hospitalization was 40.0 days
      in 1988 and 38.3 days in 1989. Patients with limb amputation stayed significantly
      longer in the hospital than patients without amputation (p < 0.001). Overall in
      hospital mortality was 10%. Mortality was highest in patients staged Wagner 4 +
      5. Mortality among patients staged Wagner 1 and 2 was higher than in patients
      with osteomyelitis (p < 0.001). Of all patients, approximately 10% were
      discharged to a rehabilitation centre or nursing home. CONCLUSION: Both the mean
      age of the patients hospitalized and the total amount of costs involved are
      higher than put forward previously in studies from the US Diabetic foot problems
      put a heavy burden on the health status of elderly diabetic patients. Financial
      resources should be reallocated in the direction of preventive health care.

PMID- 8261074
TI  - Relationship between birth weight and umbilical Doppler blood flow velocity
      waveforms during the third trimester of pregnancy.
AB  - OBJECTIVES: The Doppler ultrasound method for recording blood flow velocity
      waveforms in the fetal umbilical arteries is now widely used as an indicator of
      fetal well-being. This study was conducted to investigate the impact of umbilical
      placental resistance level on fetal growth development. METHODS: Maximal flow
      velocity waveforms were recorded from the umbilical artery in 108 pregnant women
      including 50 with normal pregnancies, 3 with previous death in utero, and 55 with
      moderate arterial hypertension corrected by resting only. All the newborn infants
      had a normal birth weight (BW between the 10th and the 90th percentile for the
      gestational age at birth). Doppler measurements were performed between 25 to 38
      weeks of gestation. The placental resistance index (PRI) derived from blood flow
      velocity measurements was determined. RESULTS: Data were grouped in two-week
      intervals according to the age of gestation at Doppler examination. We found an
      inverse close relationship between BW and PRI which can be described by a linear
      function of PRI in each interval. BW increased with the decrease in PRI.
      CONCLUSIONS: Our findings suggest that umbilical placental resistance level
      determines fetal growth development and birth weight during pregnancies without
      placental insufficiency.

PMID- 8261075
TI  - Diagnosis of cytomegalovirus infections of the nervous system by
      immunocytochemical demonstration of infected cells in cerebrospinal fluid.
AB  - OBJECTIVES: Infections caused by the cytomegalovirus (CMV) are frequent
      complications in patients with the acquired immunodeficiency syndrome. Diagnosis
      of CMV infections of the nervous system is still difficult. METHODS: We evaluated
      immunocytochemical staining for a CMV early antigen in cells prepared from the
      cerebrospinal fluid of patients with clinical evidence for neural CMV infections
      and from controls. RESULTS: CMV positive cells were found in four samples of
      patients with clinical evidence of CMV infection. Three of these patients were
      suffering from myeloradicalitis, one had a severe brain stem encephalitis. No CMV
      positive were found in controls. CONCLUSIONS: Immunocytochemical staining of CSF
      cells may be helpful in the diagnosis of CMV infection of the central nervous
      system and of the nerve roots.

PMID- 8261076
TI  - A clinical, genetic and echocardiographic study of hypertrophic cardiomyopathy in
      a large family.
AB  - OBJECTIVES: To confirm recent reports on the incidence of human lymphocyte
      antigens (HLA) in familial hypertrophic cardiomyopathy and to better define the
      genetic patterns found in these patients. METHODS: A large family (31 members,
      18M, 13F, age range 6-80 years) with a high incidence of hypertrophic
      cardiomyopathy was screened for HLA, dermatoglyphic patterns and blood subtyping.
      RESULTS: Our finding show variable expression of the disease and reduced
      penetrance. No linkage between the disease-causing gene and HLA loci could be
      demonstrated in the family. There was no specific haplotype which present in all
      affected individuals and missing in all controls. Haplotype A2 B18 was the most
      commonly encountered in affected individuals but was absent in IV 3 and present
      in a few controls. No linkage was found between the disease-responsible gene and
      the blood groups. Finally, no typical pattern emerged from the dermatoglyphic
      studies. CONCLUSION: The genetic assessment of this family, in agreement with
      other European studies, showed no clear correlation between hypertrophic
      cardiomyopathy and blood groups ABO, Rh, Lewis, Duffy and was unable to show
      atypical or unusual dermatoglyphic patterns.

PMID- 8261077
TI  - Recanalization of chronic arterial occlusions: low-speed rotational angioplasty.
      5 years experience in peripheral and coronary vessels.
AB  - Chronic complete occlusions still represent the major technical limitation of
      percutaneous transluminal angioplasty, both in peripheral and coronary vessels.
      The clinical use of low-speed rotational angioplasty started in 1986 for the
      peripheral and in 1987 for the coronary arteries, and has already become part of
      the clinical routine in several centres. Up to now more than 350 patients with
      peripheral and 250 patients with coronary occlusions have been treated in
      Frankfurt; a multicentre questionnaire already contains information about 1,252
      patients with peripheral vessel obstructions. In peripheral occlusions the acute
      success rate was more than 80% if low speed rotational angioplasty was used as
      the first attempt; after failure of conventional techniques still more than 60%
      of the vessels could be recanalized successfully. In addition to occlusions of
      the arteries of the lower limb, indications now may include the iliac artery and
      the subclavian artery. In each of the patients with chronic coronary occlusions
      an attempt with conventional techniques had failed before. Following a learning
      curve, which was also influenced by a better understanding of morphological
      preconditions, the acute success has now reached 70%. Both in patients with
      peripheral and those with coronary occlusions the technique turned out to be a
      safe procedure. Early angiographically documented long-term results in both
      indications are comparable with conventional balloon techniques. It is concluded
      that the use of low-speed rotational angioplasty (ROTACS) can improve the results
      of non-operative invasive treatment, both in peripheral and in coronary arteries.

PMID- 8261078
TI  - Opsoclonus-myoclonus syndrome: an autopsy study of three cases.
AB  - Opsoclonus-myoclonus is a rare clinical syndrome. We report three patients who
      died with a pure opsoclonus-myoclonus syndrome. The presentation, management and
      associations of this distinctive condition are discussed, and the results of
      detailed pathological examination described. In each case the only abnormality
      was perivascular collections of lymphocytes widely distributed in the brain. This
      supports an immune-mediated rather than structural aetiology.

PMID- 8261079
TI  - Hypocalcaemia due to parathyroid metastases.

PMID- 8261080
TI  - Sarcoidosis presenting as isolated giant splenomegaly.

PMID- 8261081
TI  - Tricuspid endocarditis and Ebstein's anomaly in an intravenous drug abuser.

PMID- 8261082
TI  - Ventricular tachycardia associated with acute hepatitis A infection.

PMID- 8261083
TI  - Multiple pulmonary infections in a patient with acquired immunodeficiency
      syndrome.

PMID- 8261084
TI  - Disseminated Rhodotorula rubra infection in an HIV-infected drug abuser.

PMID- 8261085
TI  - Carcinogenesis by human papillomaviruses.

PMID- 8261086
TI  - Formation of specific efferent connections in organotypic slice cultures from rat
      visual cortex cocultured with lateral geniculate nucleus and superior colliculus.
AB  - Cells in the cerebral cortex project to many distant regions in the brain. Each
      cortical target receives input from a specific population of cells which have a
      characteristic morphology and which are located in a distinct cortical layer. In
      an attempt to learn about the mechanisms by which this stereotypic output pattern
      is generated during development, we have studied the formation of cortical
      projections in an in vitro system. Slices from developing rat visual cortex were
      cocultured with slices from the superior colliculus, the major target of cells in
      layer 5, and the lateral geniculate nucleus, the major target of cells in layer
      6. Cortical neurons which established connections with tectal and thalamic
      explants were retrogradely labelled with fluorescent dyes. It was found that, in
      vitro, different populations of neurons project to these two targets, and that
      the laminar position and cellular morphology of the projecting cells were similar
      to their in vivo counterparts. These specific connections were established when
      the target explants were placed either next to the white matter or next to the
      pial side of cortical slice cultures. The axons of cells projecting to ectopic
      positioned explants reoriented their trajectories and grew through the cortical
      grey matter directly towards their targets. Thus subcortical targets exert an
      orienting effect specifically on their innervating cells and attract growing
      axons of the appropriate cells at a distance. These results suggest that
      different targets release different molecules that act selectively on specific
      populations of neurons. Therefore, chemotropic guidance is likely to play a
      significant role in the development of specific connections between cortical
      neurons and their target areas.

PMID- 8261087
TI  - Injury-induced regulation of ciliary neurotrophic factor mRNA in the adult rat
      brain.
AB  - Ciliary neurotrophic factor (CNTF) is a pleiotropic molecule that acts as a
      neurotrophic factor for a wide range of embryonic neurons as well as a
      differentiation factor for sympathetic neuroblasts and O2A progenitor cells in
      culture. CNTF messenger RNA (mRNA) is present at very low levels in the normal
      adult rat central nervous system (CNS), but is dramatically up-regulated after an
      aspiration lesion of dorsal hippocampus and overlying cortex, in the area
      coincident with glial scar. The increased level of CNTF mRNA in lesioned
      hippocampus is maximal by 3 days and is sustained for up to 20 days, the longest
      time point examined. In contrast, mRNA levels for brain-derived neurotrophic
      factor (BDNF) and neurotrophin-3 (NT-3) were slightly decreased during the same
      period. In situ hybridization experiments revealed that cells expressing CNTF
      mRNA were concentrated at the margin of the wound, and also present within the
      gelfoam which filled the lesion cavity. This distribution of CNTF-expressing
      cells corresponded very closely to that of cells expressing high levels of glial
      fibrillary acidic protein mRNA at the wound site. Paralleling the observed
      increase in CNTF mRNA, increased levels of CNTF-like neurotrophic activity were
      apparent in soluble extracts of the lesioned tissues. This neurotrophic activity
      for ciliary ganglion neurons was completely blocked by the addition of
      neutralizing antiserum against CNTF. Basic fibroblast growth factor, which has
      been shown by others to increase after a similar lesion paradigm (Frautschy et
      al., Brain Res., 553, 291-299, 1991), does not contribute appreciably to this
      trophic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261088
TI  - The L2/HNK-1 carbohydrate mediates adhesion of neural cells to laminin.
AB  - The L2/HNK-1 carbohydrate epitope shared by several neural adhesion molecules has
      been implicated in cell-to-cell and cell-to-laminin adhesion (Keilhauer et al.,
      Nature, 316, 728-730, 1985; Kunemund et al., J. Cell Biol., 106, 213-223, 1988).
      As demonstrated previously for chicken retinal ganglion cells (Cole et al.,
      Neurosci. Lett., 93, 170-175, 1988), cerebral cortex astrocytes or cerebellar
      neurons could not be shown to adhere to the substrate-bound L2/HNK-1
      carbohydrate. The cell-bound L2/HNK-1 carbohydrate, however, was a potent
      mediator of astrocytic and neuronal cell adhesion to laminin, which was strongly
      reduced in the presence of the L2/HNK-1 carbohydrate-carrying glycolipids or Fab
      fragments of a monoclonal antibody against it. Inhibition of adhesion could not
      be observed in the presence of the negatively charged gangliosides or sulphatide,
      but in the presence of heparin. To investigate whether the L2/HNK-1 carbohydrate
      and heparin use the same or different binding sites on laminin, adhesion of cells
      to laminin was determined in the presence of heparin and Fab fragments of a
      monoclonal L2 antibody, which gave an additive value of inhibition as compared to
      the inhibition caused by the single compounds. This result, as well as studies of
      the binding of the L2/HNK-1 glycolipids to laminin in the presence of heparin,
      indicates that the L2/HNK-1 carbohydrate and heparin are implicated in different
      aspects of neural cell adhesion to laminin.

PMID- 8261089
TI  - Optical recording of neuronal activity in the insect central nervous system:
      odorant coding by the antennal lobes of honeybees.
AB  - Voltage-sensitive dyes and activity-dependent intrinsic optical signals were used
      to study the spatio-temporal activity in the antennal lobes of honeybees. The
      intrinsic signals are somewhat slower than the dye signals but show a 10-fold
      larger intensity change. These intrinsic signals consist of at least two
      components--one is wavelength-independent and the other strongly wavelength
      dependent, with a maximum at approximately 500 nm. Local inhibitory connections
      within the antennal lobes were examined by recording the activity elicited by an
      electrical stimulus to the antennal nerve of a slice preparation before and after
      applying picrotoxin to manipulate GABAergic inhibitory synapses. The inhibition
      starts with a delay of approximately 10 ms after onset of the response and has at
      least two components. The spatial distribution of the inhibition is extremely
      inhomogeneous, with areas of small inhibition adjacent to areas of large
      inhibition. Thus inhibitory interactions in the antennal lobes are not evenly
      distributed among the glomerular organization. Stimulation of an in vivo
      preparation with an odour yields a spatially restricted activity. However, the
      spatial map appears highly dynamic in time because the size of the activated area
      is a function of the time during and after the stimulus.

PMID- 8261090
TI  - Alteration of sodium currents by new peptide toxins from the venom of a
      molluscivorous Conus snail.
AB  - TxIA and TxIB, peptides with 27-amino acid residues recently isolated from the
      molluscivorous marine snail Conus textile neovicarius, exhibit strong paralytic
      activity in molluscs, with no paralytic effects on athropods and vertebrates. At
      concentrations of 0.25-0.5 microM the toxins cause spontaneous repetitive firing
      and dramatic broadening of the action potential of cultured Aplysia neurons. The
      action potential duration partially recovers within 30 min in the presence of the
      toxins. Under these conditions a second toxin application does not change the
      spike duration. TxI-induced spike broadening occurs when potassium and calcium
      conductances are blocked. Voltage-clamp experiments revealed that the toxins
      alter the kinetics of the sodium current either by slowing down the rate of
      sodium current inactivation or by recruiting silent sodium channels with slower
      activation and inactivation kinetics. The toxins shift the voltage-dependent
      steady-state Na+ current inactivation curve to more positive values by 6 mV.
      These changes are not associated with alteration in the rate of sodium current
      activation, in the peak sodium current, or the sodium current reversal potential.
      TxI apparently represents a new class of conotoxins with an unusual phylogenic
      specificity and may therefore be useful as a probe for the study of molluscan
      neuronal sodium channels.

PMID- 8261091
TI  - Currents activated by GABA and their modulation by Zn2+ in cerebellar granule
      cells in culture.
AB  - Whole-cell and single-channel currents evoked by gamma-aminobutyric acid (GABA)
      were recorded from rat cerebellar granule cells in culture. The
      electrophysiological properties of these currents were studied in control
      condition and in the presence of external Zn2+ (10-30 microM). GABA (10 microM)
      induced bicuculline-sensitive whole-cell currents which desensitized. The
      desensitization was more rapid for higher concentrations of GABA (30-300 microM).
      The current-voltage relation of GABA currents was linear from -70 to +50 mV. Two
      different types of cells were found with respect to the stoichiometry for agonist
      binding, one with Hill coefficient 1.5 and another one with coefficient 1. The
      half-maximum concentration displayed more variability, with values varying from
      10 to 50 microM. The time constant of recovery from desensitization (tau r) was
      estimated to be 36 s. Zn2+ (30 microM) blocked GABA-activated whole-cell currents
      in a non-competitive and voltage-independent way without a significant change in
      the current kinetics. In excised outside-out patches, GABA (0.5 microM) activated
      single-channel events of 19 and 31 pS. Kinetic analysis yielded two mean shut
      times (tau c1 = 2.70 ms, tau c2 = 205 ms) and one mean open time (tau o = 3.64
      ms). Zn2+ (10 microM) did not affect single-channel conductances and mean open
      and shut times, but significantly reduced the probability of opening from 0.17 to
      0.06. It is probable that Zn2+ binds to a site located on the extracellular part
      of the GABAA receptor channel complex.

PMID- 8261092
TI  - The fates of cells in the developing cerebral cortex of normal and
      methylazoxymethanol acetate-lesioned mice.
AB  - We are interested in the mechanisms that generate the mature cerebral cortex. We
      used bromodeoxyuridine (BrdU) to label cortical cells as they were being born. We
      followed the fates of specific sets of cortical precursors in normal mice and in
      mice in which other groups of cortical progenitors had been destroyed with the
      antimitotic agent methylazoxymethanol acetate (MAM Ac). In normal mice, most
      cells destined for the cerebral cortex were produced from embryonic day 12 (E12)
      to E16 in the expected inside-to-outside sequence (deep layers first, superficial
      layers last). Injection of MAM Ac at E13 killed cells that would normally have
      contributed to the deep cortical layers. As a consequence, the cortex was thinned
      by approximately 25% at postnatal day 21 (P21). However, all laminae were present
      and had normal connections with subcortical structures, although all were
      proportionately thinner. BrdU injected on E16 labelled a normally sized
      complement of cells that spanned a larger proportion of the depth of the thinned
      cortex. Thus, the deep cortical layers comprised many cells that were born
      several days later than normal. At embryonic ages prior to E12, a transient set
      of cells is produced in the early telencephalon. After injection with MAM Ac at
      E10, the cortex appeared histologically and histochemically normal at P21.
      However, many cells that would normally have contributed to superficial cortex
      (born on E15) were significantly deeper than normal. These results suggest that,
      during the early stages of cortical development, the nervous system is
      sufficiently plastic to compensate to some extent for the destruction of specific
      precursor cells by altering the fates of neurons born later. They indicate that
      the embryonic date on which a cortical cell is born does not necessarily
      determine its eventual phenotype.

PMID- 8261093
TI  - Regeneration of hypoglossal nerve axons following blockade of the axotomy-induced
      microglial cell reaction in the rat.
AB  - The aim of the present study was to examine whether inhibition of the microglial
      cell reaction around axotomized motoneurons affects the subsequent regeneration
      process of the injured axons. The microglial cell reaction in the hypoglossal
      nucleus of the rat was blocked by infusion of cytosine-arabinoside (ARA-C) into
      the ventricular system. Axon regeneration was evaluated by determining the number
      and size distribution of myelinated axons at a defined level distal to the crush
      site, the number of neurons which could be retrogradely labelled from the distal
      stump as well as the number of motor endplates in the tongue at various times
      following injury. No significant difference was observed for any of these
      parameters between ARA-C-treated and untreated animals. Therefore, it is
      concluded that the microglial cell reaction is not necessary for peripheral
      nerves to regenerate and restore target contact at a normal rate and to a normal
      extent.

PMID- 8261094
TI  - Heterogeneity of synaptic density in the adult pigmented rabbit's visual cortex.
AB  - In the adult pigmented rabbit, synaptic density in the lateral and medial part of
      the visual cortex was estimated along the projection area of the visual streak. A
      higher synaptic density distribution was observed in the lateral cortex
      (projection area of the nasal visual field) than in the medial cortex (projection
      area of the temporal visual field). This shows that there is a higher synaptic
      density in the region of the visual cortex receiving input from a retinal area
      with a high ganglion cell concentration than the area of the cortex receiving
      input from the retina with a low concentration of such cells. The regions of the
      visual cortex with higher and lower synaptic densities are the areas having a
      higher and lower magnification factor respectively.

PMID- 8261095
TI  - Tonic activation of NMDA receptors causes spontaneous burst discharge of rat
      midbrain dopamine neurons in vivo.
AB  - Midbrain dopamine neurons in vivo discharge in a single-spike firing pattern or
      in a burst-firing pattern. Such activity in vivo strikingly contrasts with the
      pacemaker activity of the same dopamine neurons recorded in vitro. We have
      recently shown that burst activity in vivo of midbrain dopamine neurons is due to
      the local activation of excitatory amino acid receptors, as microapplication of
      the broad-spectrum antagonist of excitatory amino acids, kynurenic acid, strongly
      regularized the spontaneous firing pattern of these dopamine neurons. In the
      present study, we investigated which subtypes of excitatory amino acid receptors
      are involved in the burst-firing of midbrain dopamine neurons in chloral hydrate
      anaesthetized rats, iontophoretic or pressure microejections of 6-cyano, 7
      nitroquinoxaline-2,3-dione (CNQX), a non-N-methyl-D-aspartate (NMDA) receptor
      antagonist, did not alter the spontaneous burst firing of dopamine neurons (n =
      36). In contrast, similar ejections of (+-)2-amino,5-phosphonopentanoic acid (AP
      5), a specific antagonist at NMDA receptors, markedly regularized the firing
      pattern by reducing the occurrence of bursts (n = 52). In addition, iontophoretic
      ejections of NMDA, but not kainate or quisqualate, elicited a discharge of these
      dopamine neurons in bursts (n = 20, 12 and 14, respectively). These data suggest
      that burst-firing of midbrain dopamine neurons in vivo results from the tonic
      activation of NMDA receptors by endogenous excitatory amino acids. In view of the
      critical dependency of catecholamine release on the discharge pattern of source
      neurons, excitatory amino acid inputs to midbrain dopamine neurons may constitute
      a major physiological substrate in the control of the dopamine level in target
      areas.

PMID- 8261096
TI  - Differential visualization of dopamine D2 and D3 receptor sites in rat brain. A
      comparative study using in situ hybridization histochemistry and ligand binding
      autoradiography.
AB  - At least five members of the dopamine receptor family have been characterized at
      the gene level. D2, D3 and D4 dopamine receptors are related pharmacologically.
      In order to visualize the differential expression of D1, D2 and D3 receptors in
      rat brain we have combined in situ hybridization histochemistry with receptor
      autoradiography. Regions enriched with D3 messenger RNA (mRNA) included the
      islands of Calleja (ioC) and nucleus accumbens. Very low or undetectable levels
      were present in the caudate-putamen. In contrast, no D2 transcripts were observed
      in the islands of Calleja, but there were high levels in the nucleus accumbens,
      caudate-putamen (CP) and pyramidal layer of the olfactory tubercle. A comparison
      of the binding pattern of six dopamine receptor radioligands hitherto regarded as
      D2 receptor-selective showed that the islands of Calleja were intensely labelled
      by [125I]iodosulpride, [3H]CV 205 502 and [3H]SDZ 205 501, while the binding of
      [3H]spiperone, [3H]raclopride and [3H]YM 09151-2 was much lower or undetectable.
      Pharmacological analysis of the binding of D2/D3 ligands to the islands of
      Calleja and caudate-putamen suggests that binding sites in these two regions are
      of different pharmacology, consistent with the presence of D3 sites in the
      islands of Calleja and the predominance of D2 sites in the caudate. These results
      demonstrate the expression of D3 binding sites in the rat brain and provide a
      procedure to differentiate D2 and D3 receptor populations in binding studies.

PMID- 8261097
TI  - Acute and chronic phases of unilateral inflammation in rat's ankle are associated
      with an increase in the proportion of calcitonin gene-related peptide
      immunoreactive dorsal root ganglion cells.
AB  - Using immunocytochemical methods, the proportion of calcitonin gene-related
      peptide immunoreactive perikarya was determined in dorsal root ganglia L4-L6 in
      four control rats and in ten rats with a unilateral inflammation in the ankle
      region of the left hindlimb. The inflammation was induced by subdermal injection
      of Freund's complete adjuvant at the ankle. Swelling and cellular infiltration of
      the ankle region developed within 2 days, and were stable and restricted to the
      injected ankle for the duration of the 3-week study. In control rats
      approximately 24% of 20,419 perikarya showed calcitonin gene-related peptide
      (CGRP)-like immunoreactivity. In rats with unilateral inflammation the proportion
      of CGRP-positive neurons was increased on the inflamed side to approximately 32%
      of 11,454 cells at day 2 (P < 0.001 with respect to ganglia in normal rats) and
      approximately 29% of 10,739 perikarya at day 20 post inoculation (P < 0.01). By
      contrast, no significant changes were found between ganglia in the non-injected
      side (approximately 25% at day 2 and approximately 24% at day 20). These results
      demonstrate that peripheral inflammation is associated with an increase in the
      proportion of neurons in the dorsal root ganglia that synthetize CGRP. This up
      regulation is already present at an early stage of inflammation but also at later
      stages, suggesting that the increased synthesis of CGRP is an important
      neurobiological reaction associated with the acute and chronic phases of
      inflammation.

PMID- 8261098
TI  - Mediation of thalamic sensory responses in vivo by ACPD-activated excitatory
      amino acid receptors.
AB  - The existence of the so-called metabotropic excitatory amino acid receptor has
      been known for some years. Various functions have been suggested for this
      receptor, but the lack of selective antagonists for (IS, 3R)-aminocyclopentane
      dicarboxylic acid (ACPD) has precluded the direct demonstration of a functional
      role for this receptor in synaptic processes. We describe here a specific
      antagonism of the excitatory responses of thalamic neurons to ACPD by two novel
      antagonists, and a parallel antagonism by these compounds of sensory synaptic
      responses to noxious stimuli of the same neurons. This provides the first direct
      pharmacological evidence for a functional role of ACPD-sensitive receptors in
      central neurotransmission, and indicates that these receptors may play an
      important part in central sensory processes.

PMID- 8261099
TI  - Long fibre growth by axons of embryonic mouse hippocampal neurons
      microtransplanted into the adult rat fimbria.
AB  - We have described a method for the microtransplantation of a suspension of a few
      thousand cells from mid to late embryonic mouse hippocampi into the fimbria of
      immunosuppressed adult rat hosts. There was close graft-to-host contact, across a
      non-scarred interface. The transplanted cells included CA3 type pyramids, and
      were enclosed within the host myelinated fibre tract, whose glial framework was
      largely undisturbed. Immunohistochemistry of two species-specific markers (M6 and
      Thy-1.2) showed that the donor mouse neurons grew fine (< 0.5 micron diameter)
      axons which extended singly or in fascicles through the rat host fimbria for a
      maximum distance of at least 10 mm. The donor axons were intimately integrated
      among and closely aligned to the host tract axons and to the interfascicular
      glial rows of the host tract. The axons travelled (i) laterally through the
      ipsilateral fimbria, (ii) medially across the midline in the ventral hippocampal
      commissure to reach the contralateral fimbria and alveus, and (iii) rostro
      medially to the septum. On approaching the terminal fields appropriate to
      hippocampal CA3 pyramidal cell axons, the transplant axons gave rise to fine
      preterminal branches which were continuous with a reticular or amorphous
      immunoreactivity in the stratum oriens and stratum pyramidale of the ipsilateral
      hippocampus, and in the lateral and triangular septal nuclei. The donor axons
      extended along the host fimbria at a rate of approximately 1 mm per day, reaching
      their terminal field destinations by approximately 1-2 weeks. At 7 weeks the
      projections were maintained, but with little further extension. These
      observations indicate that the microenvironment of myelinated adult fibre tracts
      is permissive for an abundant and rapid growth of axons from transplanted
      embryonic cell suspensions. These axons can leave host tracts to invade
      appropriate terminal fields.

PMID- 8261100
TI  - Post-transcriptional compartmentalization of acetylcholine receptor biosynthesis
      in the subneural domain of muscle and electrocyte junctions.

PMID- 8261101
TI  - Differential expression of immediate early genes in rubrospinal neurons following
      axotomy in rat.
AB  - Many immediate early genes are rapidly and transiently expressed in the central
      nervous system following a variety of stimuli. Damage to the axons of peripheral
      and certain central neurons has been shown to result in a long-term increase in
      expression of c-Jun in the parent cell bodies. In the peripheral nervous system
      this increased expression of c-Jun protein and mRNA develops over 24 h following
      sciatic nerve section and is maintained if the damaged nerve is ligated, but
      returns to basal levels if the peripheral nerve is allowed to regenerate. Here,
      we report on the response of rubrospinal neurons to spinal cord hemisection at
      levels C3 and T10. c-Jun expression was first seen at 12 h post-lesion in a
      limited number of rubral neurons. The number of positively stained neurons
      increased up to 10 days post-lesion and then declined over the following weeks.
      By 7 weeks post-lesion there was still evidence of c-Jun immunoreactivity in both
      large and other clearly atrophic rubrospinal neurons. c-Fos immunoreactivity was
      seen only at 12-48 h in a small number of rubrospinal neurons. Evidence from
      retrograde tracing experiments following fluorogold application to the hemisected
      cord suggested that all c-Jun-positive neurons projected into the spinal cord. No
      c-Jun response was seen following a lesion at T10.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8261102
TI  - Cytochemical redistribution of 5'-nucleotidase in the developing cat visual
      cortex.
AB  - The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to
      undergo a marked redistribution during development of the cat visual cortex and
      to be involved in the remodelling of ocular dominance columns (Schoen et al., J.
      Comp. Neurol., 296, 379-392, 1990). Using an enzyme-cytochemical technique, we
      now investigate the developmental redistribution of 5'-nucleotidase activity in
      area 17 of kittens at the ultrastructural level. Between postnatal days 35 and
      42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product
      occupies the clefts of asymmetrical synapses within the neuropil. During later
      development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all
      cortical laminae, the enzyme disappears from its synaptic localization and
      becomes increasingly associated with astrocytic membranes. The transient
      appearance of 5'-nucleotidase at synapses parallels the time-course and laminar
      profile of the synaptic remodelling which takes place during the critical period
      of visual cortex development. This suggests that synapse-bound 5'-nucleotidase
      activity plays a role in synaptic malleability, whereas its later association
      with glial profiles is likely to reflect other functions of the enzyme.

PMID- 8261103
TI  - The incidence of bifurcation among corticocortical connections from area 17 in
      the developing visual cortex of the cat.
AB  - In newborn kittens, cells in the striate cortex (visual area 17) that project to
      area 18 (part of extrastriate cortex) are distributed with uniform density in the
      superficial and in the deep layers. During postnatal weeks 2-3, some of these
      corticocortical connections are removed to generate an adult-like projection in
      which association cells are clustered mainly in the superficial layers of area
      17. Axonal elimination, without cell death, is the major factor sculpting patches
      of corticocortical cells in superficial layers. In adult cats, few cells in area
      17 (approximately 5%) have axons that bifurcate to multiple extrastriate areas.
      We have studied the possibility that the early exuberant innervation of area 18
      by neurons in area 17 is largely from the transient collaterals of axons that
      also project to other visual areas. Kittens aged 2-21 days were each injected
      with a pair of retrogradely transported tracers, either diamidino yellow and fast
      blue, or diamidino yellow and a carbocyanine dye, at retinotopically
      corresponding points in area 18 and either area 19 or the posteromedial lateral
      suprasylvian cortex (PMLS). As for injections in area 18, those in area 19 and
      PMLS in kittens aged < or = 5 days labelled cells in continuous bands in area 17;
      in older kittens neurons projecting from area 17 to extrastriate regions were in
      patches, mainly in superficial layers. In each animal, the labelling from the two
      injections overlapped by 51-92%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261104
TI  - Long-term effects of selective target removal on brainstem premotor neurons in
      the adult cat.
AB  - The electrical activity of antidromically identified abducens internuclear
      neurons selectively deprived of their target motoneurons was recorded in chronic
      alert cats. Target motoneurons were killed by the injection of the cytotoxic
      lectin of Ricinus communis into the medial rectus muscle. Following target
      removal, the discharge pattern of abducens internuclear neurons showed an overall
      decrease in firing rate, a significant reduction in their sensitivity to eye
      position and velocity, and the presence of anomalous responses such as bursts of
      spikes associated with off-directed saccades. The decreased excitability of
      abducens internuclear neurons correlated well with a marked reduction in the
      synaptic efficacy of their inputs. Thus, both excitatory and inhibitory synaptic
      potentials of vestibular origin showed a noticeable decrease in amplitude. The
      alterations in firing properties and synaptic transmission were only observed
      during an initial period of 3 weeks following ricin injection. Within 1 month the
      electrophysiological parameters returned to control values and remained unaltered
      for 1 year. Retrograde labelling of abducens internuclear neurons revealed that
      no cell death occurred after target loss. The anterograde axonal labelling of
      these neurons showed a progressive decrease in the density of their axonal
      terminals, and no sign of redistribution to other areas was found. These findings
      indicate that abducens internuclear neurons are not dependent on the presence of
      their natural target cells, either for the survival or for the maintenance of
      appropriate physiological signals.

PMID- 8261105
TI  - Cholecystokinin in mammalian primary sensory neurons and spinal cord: in situ
      hybridization studies in rat and monkey.
AB  - The peptide cholecystokinin (CCK) has been suggested to be involved in
      nociception, but its exact localization at the level of the spinal cord and in
      spinal ganglia has been a controversial issue. Therefore the distribution of
      messenger RNA (mRNA) for CCK was studied by in situ hybridization using
      oligonucleotide probes on sections of adult rat lumbar dorsal root ganglia
      following unilateral section of the sciatic nerve and on sections of untreated
      monkey trigeminal ganglia, spinal cord and spinal ganglia from all levels. For
      comparison, calcitonin gene-related peptide (CGRP) mRNA was also studied in the
      monkey tissue using the same techniques. Peripheral sectioning of the sciatic
      nerve in the rat resulted in the appearance of detectable CCK mRNA in up to 30%
      of remaining ipsilateral L4 and L5 dorsal root ganglion neurons 3 weeks after
      surgery, with a distinct but more limited appearance also in the contralateral
      ganglia. No cells, or only single cells, could be seen in normal control rat
      ganglia. In contrast, in the normal monkey, approximately 20% of dorsal root
      ganglion neurons, regardless of spinal level, and 10% of trigeminal ganglia
      neurons expressed mRNA for CCK. CGRP mRNA was expressed at detectable levels in
      approximately 80% of these monkey dorsal root ganglion neurons. In the monkey
      spinal cord, CCK mRNA was detected in the dorsal horn and in motoneurons, whereas
      CGRP mRNA was only seen in motoneurons. The present results suggest that CCK
      peptides can be involved in sensory processing in the dorsal horn of the spinal
      cord in normal monkeys and in rats after peripheral nerve injury, adding one more
      possible excitatory peptide to the group of mediators in the dorsal horn.

PMID- 8261106
TI  - Electrophysiological and pharmacological characterization of vestibular inputs to
      identified frog abducens motoneurons and internuclear neurons in vitro.
AB  - Synaptic vestibular inputs of antidromically identified motoneurons and
      internuclear neurons in the abducens nucleus were studied electrophysiologically
      and pharmacologically in the isolated brain of grass frogs (Rana temporaria). The
      prevailing response pattern of abducens motoneurons (AbMOT) following stimulation
      of the VIIIth nerve was crossed disynaptic excitation and uncrossed disynaptic
      inhibition. A few AbMOT (five of 46), however, exhibited uncrossed excitation
      instead of inhibition. Abducens internuclear neurons (AbINT), identified by
      antidromic activation following stimulation of the contralateral medial
      longitudinal fascicle, exhibited disynaptic response patterns to stimulation of
      the VIIIth nerve that were very similar in latency and rise time to those of
      AbMOT except for the absence of uncrossed disynaptic inhibition. Bath application
      of strychnine (50 microM), a glycine antagonist, blocked the uncrossed inhibitory
      vestibular input to AbMOT and AbINT completely and reversibly, whereas picrotoxin
      (100 microM), a GABA (gamma-aminobutyric acid) antagonist, had no detectable
      effect on these disynaptic potentials. These results suggest glycine as the
      transmitter of inhibitory vestibular projections onto AbMOT and AbINT. The
      pharmacology of the excitatory vestibular input of these neurons was studied by
      electrical stimulation of the vestibular nuclear complex. Crossed monosynaptic
      excitatory inputs in AbMOT and AbINT were blocked completely by CNQX (6-cyano-7
      nitroquinoxaline-2,3-dione) (10 microM), an antagonist of AMPA (alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, indicating glutamatergic
      excitation. Comparison of these results with those in the cat suggests the
      presence of a basic horizontal vestibulo-ocular reflex that is very similarly
      organized, and corroborates the hypothesis that major behavioural differences in
      the performance of compensatory eye movements between species result from the
      properties of supplementary networks and not from differences in a common 'three
      neuron' vestibulo-ocular arc.

PMID- 8261107
TI  - The structure of sleep is related to the learning ability of rats.
AB  - Using electroencephalographic methods, rats learning or not learning a two-way
      active avoidance task were found to differ significantly in the structure of
      sleep determined the day before training. The main differences concerned (i)
      synchronized sleep episodes followed by wakefulness, which were longer and fewer
      in learning rats; (ii) paradoxical sleep episodes, which were longer in learning
      rats. Significant correlations were present between the number and/or the average
      duration of synchronized sleep episodes followed by wakefulness or by paradoxical
      sleep and the number of avoidances or escapes scored in the training session.
      Power spectral analysis indicated that the relative output in the 6-7-Hz region
      was higher in learning rats, notably during short episodes of synchronized sleep
      followed by paradoxical sleep. As two-way active avoidance training induces
      comparable modifications in postacquisition sleep (Ambrosini et al., Physiol.
      Behav., 51, 217-226, 1992), the features of preacquisition sleep which prevail in
      learning rats might directly determine their capacity to learn. Alternatively,
      they might reflect the existence of a genetic determinant independently
      conditioning the ability to learn.

PMID- 8261108
TI  - Cocaine enhances the changes in extracellular dopamine in nucleus accumbens
      associated with reinforcing stimuli: a high-speed chronoamperometric study in
      freely moving rats.
AB  - Numerous data suggest that the mesocorticolimbic dopamine (DA) system is
      critically involved in the organization and regulation of goal-directed
      behaviours of various types as well as in the mediation of the psychogenic
      effects of cocaine. To test the hypothesis that cocaine not only alters levels of
      extracellular DA within the mesolimbic DA system, but in addition changes the
      response of this system to reinforcing environmental stimuli, a study using high
      speed chronoamperometry was done to evaluate the effects of cocaine (15 mg/kg,
      i.p.) on extracellular DA in the nucleus accumbens and to assess the effects of
      cocaine on the response evoked by the presentation of tail-pinch and palatable
      food. Cocaine was found to induce long-term biphasic changes in extracellular DA
      (an increase followed by a decrease) and, more importantly, to enhance DA
      increases evoked by both tail-pinch and food. The powerful enhancing action of
      cocaine on DA release, triggered by significant environmental stimuli and
      associated with behaviours of different types, is considered to be a possible
      primary mechanism of its rewarding or euphorigenic effect.

PMID- 8261109
TI  - The glia-derived protease nexin 1 persists for over 1 year in rat brain areas
      selectively lesioned by transient global ischaemia.
AB  - The re-expression of the developmentally regulated serine protease inhibitor glia
      derived nexin (GDN) was investigated 1 year after transient global ischaemia
      induced by the four-vessel occlusion technique in rats. The CA1 sector of the
      hippocampus was severely shrunken due to the absence of pyramidal cells, but
      still clearly discernible due to the continued presence of the parvalbumin
      containing GABAergic neurons. In this partially neuron-depleted hippocampus, GDN
      immunoreactivity was found in reactive astrocytes containing glial fibrillary
      acidic protein. GDN-positive astrocytes were also found in other lesioned areas,
      the reticular thalamic nucleus and the cerebellar cortex. Thus, the re-expression
      of GDN in the adult excitotoxically lesioned brain described previously in the
      gerbil model of ischaemia persists. The continued presence of the protease
      inhibitor might disturb the proteolytic balance and lead to the deposition of
      pathological breakdown products of proteins, e.g. beta-amyloid.

PMID- 8261110
TI  - Localization of janusin mRNA in the central nervous system of the developing and
      adult mouse.
AB  - Janusin (formerly termed J1-160/180) is an oligodendrocyte-derived extracellular
      matrix molecule which is restricted to the central nervous system and which is
      expressed late during development (Pesheva et al., J. Cell Biol., 1765-1778,
      1989). To gain insights into the molecule's morphogenetic functions and to
      identify its cellular source in vivo, we have studied the localization of janusin
      messenger RNA in the optic nerve, retina and spinal cord and the expression of
      janusin protein in the spinal cord of developing and adult mice. Moreover, we
      have analysed optic nerve cell cultures and retinal cell suspensions in double
      labelling experiments using a janusin-specific anti-sense complementary RNA probe
      and cell type-specific antibodies to identify the cell types containing janusin
      transcripts. In developing animals, oligodendrocytes were strongly labelled with
      the janusin anti-sense cRNA probe during the period of myelination. The number of
      labelled cells and intensity of the hybridization signal decreased significantly
      with increasing age. Interestingly, expression of janusin was not confined to
      oligodendrocytes. Some neuronal cell types and type-2 astrocytes present in optic
      nerve cell cultures also contained janusin transcripts. In contrast to
      oligodendrocytes, the number and labelling intensity of neurons containing
      janusin transcripts remained constant during postnatal development and into
      adulthood. Expression of janusin protein in the spinal cord was developmentally
      regulated, with a peak of expression in 2- or 3-week-old animals. The molecule
      was visible in the white and grey matter. In myelinated regions, it was
      associated with myelinated fibres and accumulated at nodes of Ranvier. These
      observations suggest that janusin may be of functional relevance for myelination.

PMID- 8261112
TI  - Changes in nuclear 3,5,3'-triiodothyronine receptor expression in rat dorsal root
      ganglia and sciatic nerve during development: comparison with regeneration.
AB  - The action of the thyroid hormones on responsive cells in the peripheral nervous
      system requires the presence of nuclear triiodothyronine receptors (NT3R). These
      nuclear receptors, including both the alpha and beta subtypes of NT3R, were
      visualized by immunocytochemistry with the specific 2B3 monoclonal antibody. In
      the dorsal root ganglia (DRG) of rat embryos, NT3R immunoreactivity was first
      discretely revealed in a few neurons at embryonic day 14 (E14), then strongly
      expressed by all neurons at E17 and during the first postnatal week; all DRG
      neurons continued to possess clear NT3R immunostaining, which faded slightly with
      age. The peripheral glial cells in the DRG displayed a short-lived NT3R
      immunoreaction, starting at E17 and disappearing from the satellite and Schwann
      cells by postnatal days 3 and 7 respectively. In the developing sciatic nerve,
      Schwann cells also exhibited transient NT3R immunoreactivity restricted to a
      short period ranging from E17 to postnatal day 10; the NT3R immunostaining of the
      Schwann cells vanished proximodistally along the sciatic nerve, so that the
      Schwann cells rapidly became free of detectable NT3R immunostaining. However,
      after the transection or crushing of an adult sciatic nerve, the NT3R
      immunoreactivity reappeared in the Schwann cells adjacent to the lesion by 2
      days, then along the distal segment in which the axons were degenerating, and
      finally disappeared by 45 days, when the regenerating axons were allowed to re
      occupy the distal segment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261111
TI  - ME1 and GE1: basic helix-loop-helix transcription factors expressed at high
      levels in the developing nervous system and in morphogenetically active regions.
AB  - Several class A basic helix-loop-helix (bHLH) transcription factors have been
      cloned from the developing mouse and chick nervous system. The cloned cDNAs (ME1,
      ME2, ME3, ME4, in the mouse and GE1, GE2 in the chick) have HLH coding regions
      highly homologous to other known class A bHLH genes. The genes corresponding to
      ME1 and GE1 are abundantly expressed during development of the central nervous
      system. ME1 and GE1 are expressed in proliferating neuroblasts and in cells at
      the initial stages of differentiation (for example in the external granule cell
      layer of the cerebellum and in the lateral region of the ventricular zone in the
      developing neural tube and cortex). They are also expressed at high levels in
      morphogenetically active regions such as limb buds, somites and mesonephric
      tubules. The expression of ME1 and GE1 decreases once cellular differentiation is
      over. Based on the expression of ME1 and GE1 in regions of active cellular
      proliferation and differentiation and on the known role of other bHLH factors in
      development, we suggest that ME1 and GE1 play important roles during development
      of the nervous system as well as in other organ systems.

PMID- 8261113
TI  - Effect of thiol reagents on phosphoinositide hydrolysis in rat brain
      synaptoneurosomes.
AB  - Some divalent ions, such as Cd2+ and Zn2+, are able to stimulate phosphoinositide
      (PI) breakdown and to inhibit receptor-mediated PI metabolism. These ions are
      also known to react with the free -SH groups of proteins. This prompted us to
      investigate the effects of more potent sulphydryl reagents, Hg2+ and p
      chloromercuric benzosulphonic acid (PCMBS), on the inositol phosphate (IP)
      accumulation triggered by the neuroactive substances: glutamate, carbachol and
      K+, using synaptoneurosomes from 8-day-old rat forebrains. Hg2+ and PCMBS,
      depending on their concentration, had two distinct effects on IP accumulation: at
      low doses, Hg2+ (from 1 to 10 microM) and PCMBS (0.1 mM) by themselves stimulated
      PI breakdown, inhibited glutamate-elicited IP accumulation and had additive
      effects with respect to carbachol-induced IP stimulation. At higher doses, Hg2+
      (from 0.01 to 1 mM) inhibited both basal and neuroactive substance-stimulated IP
      accumulation. PCMBS (1 mM), provoked only an inhibition of the agonist-stimulated
      IP formation. Monitoring membrane potential and intracellular Ca2+ with the
      fluorescent dyes diSC2(5) and fura2, respectively, indicated that these
      mercurials could strongly depolarize the synaptoneurosomal membrane and produce a
      Ca2+ influx dependent on extracellular Ca2+. The stimulatory effects of low
      concentrations of mercurials on PI turnover could be linked to the depolarization
      they provoke and the subsequent Ca2+ rise, which in turn is known to stimulate
      some phospholipase C enzymes. The inhibitory effects observed at high
      concentrations might be due to a loss of activity of proteins involved in PI
      breakdown, as all receptor-mediated IP accumulations were inhibited.

PMID- 8261114
TI  - Neurons in the primate superior colliculus are active before and during arm
      movements to visual targets.
AB  - The activity of single neurons in the superior colliculus was recorded while a
      rhesus monkey made arm movements to visual targets located on a screen in front
      of him. It was found that the activity of a subpopulation of cells was clearly
      related to these arm movements. The neurons began to discharge either with the
      onset of the movement, during the movement period, or well before the onset of
      electromyogram (EMG) activity and movement, and could be active for the entire
      duration of EMG activity. While the discharge pattern of some of these 'reach'
      neurons was not different for movements to different target positions, other
      cells showed graded changes in activity depending on the direction of movement.
      The peak discharge rate could rise to > 100 impulses/s. Some units received
      somatosensory input; other reach cells exhibited a visual response and/or
      presaccadic activity. It is likely that the primate superior colliculus is not
      only involved in the initiation and control of orientating movements of the eyes
      but also in reaching movements of the arms.

PMID- 8261115
TI  - The effects of monocular enucleation on ganglion cell number and terminal
      distribution in the ferret's retinal pathway.
AB  - Anterograde and retrograde tracing techniques were used to examine the effects of
      removing one eye at birth on the remaining uncrossed retinal pathway in adult
      ferrets. After enucleation, the adult number of labelled ganglion cells
      projecting ipsilaterally changed from an average of 6068 in normal pigmented
      ferrets to an average of 7813 (29% increase) in pigmented enucleates. The change
      in albino ferrets was from 1455 in normals to 2319 in enucleates (59% increase).
      Labelled cells scattered across nasal retina accounted for over half the increase
      in the uncrossed population. After neonatal enucleation, the volume of lateral
      geniculate nucleus occupied by the uncrossed projection increased substantially:
      five-fold in pigmented animals and 20-fold in albinos. These results suggest that
      neonatal removal of one eye has a greater effect on the distribution of uncrossed
      terminals than on the survival of uncrossed ganglion cells. There was also an
      increase in the total number of axons in the surviving optic nerve of both
      pigmented and albino ferrets (93,000 in enucleates compared with 79,000 in normal
      animals), which cannot be simply explained as a disruption of binocular
      competition.

PMID- 8261116
TI  - Reversal of rigidity and improvement in motor performance by subthalamic high
      frequency stimulation in MPTP-treated monkeys.
AB  - In Parkinson's disease the loss of dopaminergic neurons in the substantia nigra
      is associated with global disorganization of basal ganglia activity and, in
      particular, with increased activity of the excitatory glutamatergic neurons of
      the subthalamic nucleus. Recent experimental studies have shown that parkinsonian
      symptoms can be alleviated by selective lesioning of the subthalamic nucleus in
      monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We
      measured the effect of high-frequency stimulation of the subthalamic nucleus in
      two unilaterally MPTP-treated monkeys in order to determine whether it was
      possible to obtain reversible, gradual and controllable functional impairment of
      this structure. Clinical, mechanographic and electromyographic results
      demonstrate that this technique can alleviate parkinsonian rigidity and
      bradykinesia without causing dyskinesia or hemiballismus. This study supports the
      hypothesis that the subthalamic nucleus and its excitatory projections have an
      important role in the mechanisms sustaining the expression of parkinsonian motor
      changes, and suggests that high-frequency stimulation of the subthalamic nucleus
      could be included in treatment for parkinsonism.

PMID- 8261117
TI  - A high degree of spatial selectivity in the axonal and dendritic domains of
      physiologically identified local-circuit neurons in the dentate gyrus of the rat
      hippocampus.
AB  - The axonal and dendritic domains of neurons with extensive, locally arborizing
      axons were delineated in the dentate gyrus of the rat hippocampus. In
      horizontally cut slice preparations neurons were briefly recorded and
      subsequently filled with biocytin when one or several of the following
      physiological properties were observed: (i) high-amplitude short-latency spike
      afterhyperpolarization; (ii) lack of spike frequency adaptation; (iii) high
      firing rate in response to depolarizing current. In a sample of 14 neurons,
      sufficient dendritic and/or axonal detail was recovered to identify them as non
      principal cells, i.e. non-granule, non-mossy cells. Five distinct types of cells
      were recognized, based on the spatial distribution of dendrites, presumably
      reflecting the availability of afferents, and on the basis of the highly
      selective distribution of their axon terminals, indicating synaptic target
      selectivity. They are: (1) the hilar cell forming a dense axonal plexus in the
      commissural and association pathway terminal field (HICAP cell; horizontal axon
      extent 1.6 mm) in the inner one-third of the molecular layer, and having
      dendrites extending from the hilus to the top of the molecular layer; (2) the
      hilar cell with its axon ramifying in the perforant path terminal field (HIPP
      cell, horizontal axon extent 2.0 mm) in the outer two-thirds of the molecular
      layer, whereas its spiny dendrites were restricted to the hilus; (3) the
      molecular layer cell with its dendritic and axonal domains confined to the
      perforant path terminal zone (MOPP cell, horizontal extent of axon 2.0 mm); (4)
      the dentate basket cell (horizontal axon extent 0.9 mm) had most of its axon
      concentrated in the granule cell layer, the remainder being localized in the
      inner molecular layer and hilus; (5) the hilar chandelier cell, or axo-axonic
      cell (horizontal axon extent 1.1 mm), densely innervating the granule cell layer
      with fascicles of radially oriented terminal rows, and also forming an extensive
      plexus in the hilus. The three cell types having their somata in the hilus
      projected to granule cells at the same septo-temporal level where their cell
      bodies were located. The results demonstrate that there is a spatially selective
      innervation of the granule cells by at least five distinct types of dentate
      neurons, which terminate in several instances in mutually exclusive domains.
      Their dendrites may have access to all (HICAP cell) or only a few (e.g. HIPP and
      MOPP cell) of the hippocampal afferents. This arrangement provides a framework
      for independent interaction between the output of local circuit neurons and
      subsets of excitatory afferents providing input to principal cells.

PMID- 8261118
TI  - Subdivisions in the multiple GABAergic innervation of granule cells in the
      dentate gyrus of the rat hippocampus.
AB  - The sources of GABAergic innervation to granule cells were studied to establish
      how the basic cortical circuit is implemented in the dentate gyrus. Five types of
      neuron having extensive local axons were recorded electrophysiologically in vitro
      and filled intracellularly with biocytin (Han et al., 1993). They were processed
      for electron microscopy in order to reveal their synaptic organization and
      postsynaptic targets, and to test whether their terminals contained GABA. (1) The
      hilar cell, with axon terminals in the commissural and association pathway
      termination field (HICAP cell), formed Gray's type 2 (symmetrical) synapses with
      large proximal dendritic shafts (n = 18), two-thirds of which could be shown to
      emit spines, and with small dendritic branches (n = 6). Other boutons of the
      HICAP neuron were found to make either Gray's type 1 (asymmetrical) synapses (n =
      4) or type 2 synapses (n = 6) with dendritic spines. Using a highly sensitive
      silver-intensified immunogold method for the postembedding visualization of GABA
      immunoreactivity, both the terminals and the dendrites of the HICAP cell were
      found to be immunopositive, whereas its postsynaptic targets were GABA
      immunonegative. The dendritic shafts of the HICAP cell received synapses from
      both GABA-negative and GABA-positive boutons; the dendritic spines which densely
      covered the main apical dendrite in the medial one-third of the molecular layer
      received synapses from GABA-negative boutons. (2) The hilar cell, with axon
      terminals distributed in conjunction with the perforant path termination field
      (HIPP cell), established type 2 synapses with distal dendritic shafts (n = 17),
      most of which could be shown to emit spines, small-calibre dendritic profiles (n
      = 2) and dendritic spines (n = 6), all showing characteristics of granule cell
      dendrites. The sparsely spiny dendrites of the HIPP cell were covered with many
      synaptic boutons on both their shafts and their spines. (3) The cell with soma in
      the molecular layer had an axon associated with the perforant path termination
      field (MOPP cell). This GABA-immunoreactive cell made type 2 synapses exclusively
      on dendritic shafts (n = 20), 60% of which could be shown to emit spines. The
      smooth dendrites of the MOPP cell were also restricted to the outer two-thirds of
      the molecular layer, where they received both GABA-negative and GABA-positive
      synaptic inputs.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8261119
TI  - Giant GABAB-mediated synaptic potentials induced by zinc in the rat hippocampus:
      paradoxical effects of zinc on the GABAB receptor.
AB  - The interaction of zinc with pre- and postsynaptic GABAB receptors was studied in
      adult rat hippocampal slices using intracellular recording in CA1 and CA3
      pyramidal neurons. Zinc (50-300 microM) antagonized baclofen responses with a
      variable potency, whereas CGP-35348 (100 microM) or barium (300 microM) produced
      a more substantial and consistent inhibition. Zinc also induced giant GABAA
      mediated depolarizing potentials (GDP) in these neurons. After blocking GABAA and
      excitatory synaptic transmission, monosynaptic hyperpolarizing inhibitory
      postsynaptic potentials (IPSP) mediated by GABAB receptors (IPSPB) were inhibited
      by CGP-35348 or barium; however, zinc increased the latency and prolonged the
      duration of the IPSPB and also induced the appearance of spontaneous giant GABAB
      mediated hyperpolarizing potentials (GHP). In some cells, IPSPBs in zinc
      exhibited a multiphasic appearance. The early component was partially inhibited
      by 300 microM zinc and was followed by a late GHP. CGP-35348 at 100 microM
      inhibited the early monosynaptic IPSPB but not the GHP; however, at 300 microM
      both components were blocked. Paired-pulse inhibition of the IPSPB was used to
      assess the effect of zinc on presynaptic GABAB receptors. Neither the zinc
      chelating agent CP94 (400 microM) nor zinc affected this phenomenon. CGP-35348,
      barium and polyvalent cations, such as cadmium, copper, cobalt, manganese, iron
      and aluminum, failed to induce giant potentials in hippocampal neurons. It is
      concluded that zinc is apparently unique in synchronizing the release of GABA to
      produce GDPs and GHPs.

PMID- 8261120
TI  - Current source density profiles of optical recording maps: a new approach to the
      analysis of spatio-temporal neural activity patterns.
AB  - Spatio-temporal spreading of activity in the CA1 region of the rat hippocampal
      slice was studied by two experimental approaches. At identical locations in the
      tissue we measured both the extracellular field potential distribution with
      microelectrode recordings and the intracellular potential distribution by optical
      recording, using voltage-sensitive fluorescent dyes. Current source density
      analysis (CSD) was applied to the extracellular field potential distributions
      (eCSD) to enhance the spatial resolution. In order to obtain an analogous
      improvement for the optical recordings, we developed a new CSD transformation,
      which calculates the locations of the transmembrane current generators from the
      intracellular potential distributions (iCSD). Compared to the underlying
      fluorescence maps, the new iCSD profiles exhibit a considerable improvement in
      spatial resolution. Results can be directly interpreted in terms of physiological
      membrane processes, such as postsynaptic potentials and action potentials. The
      iCSD profiles show a surprisingly good correspondence with the classical eCSD
      profiles both qualitatively and quantitatively, the only difference being that
      cell body activity is reduced in amplitude. Thus, this new optical CSD analysis
      paves the way for a quantitative interpretation, rather than the hitherto
      predominantly qualitative interpretation of spatio-temporal activity profiles
      from optical recording measurements.

PMID- 8261121
TI  - Axonal transport of dopamine-containing vesicles labelled in vivo with
      [3H]reserpine.
AB  - Axonal transport of the vesicular monoamine transporter was assayed in the rat
      brain by in vivo binding of the specific ligand [3H]reserpine. Because of the
      marked localization of reserpine binding sites in dopaminergic cell bodies and
      nerve terminals, the dopaminergic nigrostriatal pathway was chosen for the study
      of the axonal transport of the monoamine carrier present in the membrane of
      synaptic vesicles. When labelled reserpine was injected into the substantia
      nigra, a delayed accumulation of radioactivity in the ipsilateral striatum was
      observed approximately 4 h after the injection. Similarly, injection into the
      right striatum was followed by a substantial accumulation of radioactivity in the
      ipsilateral substantia nigra, which was prevented by peripheral injection of
      unlabelled reserpine or tetrabenazine. This process was rapid and dependent on
      microtubules. In senescent rats, the amount of retrogradely transported
      [3H]reserpine was significantly reduced. These results demonstrate that labelled
      reserpine may be used to monitor in vivo fast axonal transport in central
      neurons.

PMID- 8261122
TI  - Characterization of a neurite outgrowth inhibitor expressed after CNS injury.
AB  - Reactive gliosis, a general response to injury in the central system grey and
      white matter, represents a serious obstacle to axonal regeneration in mammals. In
      culture, myelin-free plasma membranes from normal rat brain tissue promoted
      neurite outgrowth, whereas myelin-free membranes purified from injured tissue
      were inhibitory. The inhibitory activity could be solubilized by detergent, was
      sensible to glycosaminoglycan lyase digestion and eluted with an apparent
      molecular weight of 160-220 kDa in gel filtration chromatography. When presented
      as a surface-bound molecule, the inhibitor prevented neurite initiation; when
      added in a soluble form to growing neurites, it induced their retraction. These
      results provide cellular and molecular evidence supporting the classical view
      that, in the mammalian central nervous system, damage-evoked gliosis correlates
      with the expression of molecules capable of preventing neurite outgrowth.

PMID- 8261123
TI  - Effects of intracortical infusion of anticholinergic drugs on neuronal plasticity
      in kitten striate cortex.
AB  - During a critical period of postnatal development the mammalian visual cortex is
      highly susceptible to experience-dependent alterations of neuronal response
      properties. These modifications are facilitated by the neuromodulators
      noradrenaline and acetylcholine. To identify the cholinergic mechanisms
      responsible for this facilitation, muscarinic and nicotinic antagonists were
      infused into the visual cortex of kittens while the animals were subject to
      monocular deprivation. Subsequently the ocular dominance of cortical cells was
      assessed by single-unit recording. Ocular dominance changes were suppressed by
      scopolamine and pirenzepine but not by gallamine, hexamethonium and mecamylamine.
      This blocking effect was concentration-dependent, and control experiments
      revealed that it was not due to suppression of neuronal responses to light. It is
      concluded from these results that acetylcholine facilitates neuronal plasticity
      in the visual cortex through mechanisms activated by muscarinic M1 receptors.

PMID- 8261124
TI  - Retinal projections to the pretectum, accessory optic system and superior
      colliculus in pigmented and albino ferrets.
AB  - Retinal projections to the pretectal nuclei, accessory optic system and superior
      colliculus in pigmented and albino ferrets were studied using anterograde tracing
      techniques. Both Nissl- and myelin-stained material was used to identify the
      pretectal nuclei, nuclei of the accessory optic system and the layers of the
      superior colliculus. Following monocular injection of either horseradish
      peroxidase or rhodamine-B-isothiocyanate, four pretectal nuclei, including the
      nucleus of the optic tract, posterior pretectal nucleus, anterior pretectal
      nucleus and the olivary pretectal nucleus, could be identified to receive direct
      retinal input in both pigmented and albino strains. In the accessory optic
      system, retinal terminals were observed in the dorsal, lateral and medial
      terminal nuclei as well as in the interstitial nucleus of the superior
      fasciculus, posterior fibres. The retinal projection to the superior colliculus
      was found to innervate the three superficial layers. The retinal projections to
      the pretectal nuclei and nuclei of the accessory optic system in the pigmented
      animals were bilateral, although the label was most dense contralateral to the
      injected eye. Ipsilateral retinal projections to the pretectal nuclei and nuclei
      of the accessory optic system appeared to be absent in albino ferrets, i.e. they
      were invisible with our methods. In both pigmented and albino ferrets retinal
      terminals in the contralateral superior colliculus densely innervated the three
      superficial layers. In both strains the ipsilateral projection appeared as
      clusters which were absent in rostral and caudal poles. In pigmented animals the
      ipsilateral projection was much denser and more extensive than in albinos.
      Following injection of retrograde tracers into the brainstem at the level of the
      dorsal cap of the inferior olive, retrogradely labelled neurons in the pretectum
      were found in the ipsilateral nucleus of the optic tract. Their somata overlapped
      mainly with scattered retinal terminals close to the pretectal surface and rarely
      or not all with the deeper prominent terminal clusters. In the accessory optic
      system, inferior olive projecting neurons were observed in all four ipsilateral
      nuclei and fully coincided with the retino-recipient zones. In the superior
      colliculus, retrogradely labelled neurons were found contralateral to the
      injection site in the deep layers.

PMID- 8261125
TI  - Squint affects synchronization of oscillatory responses in cat visual cortex.
AB  - As shown previously, neurons in various areas of the cat's visual cortex respond
      to appropriate visual stimuli with oscillatory activity in the frequency range of
      30-70 Hz. It has been suggested that synchronization of such responses serves to
      define assemblies of coherently active cells which represent individual visual
      objects. In this study, we have investigated this putative binding mechanism in
      the visual cortex of strabismic cats. We used six adult cats in which divergent
      squint had been induced surgically at the age of 3 weeks. Multiunit activity was
      recorded from area 17 with arrays of four or five closely spaced microelectrodes.
      Subsequently, auto- and cross-correlation functions were computed for all spike
      trains. To quantify the oscillatory nature of the responses and the strength of
      synchronization between spatially remote sites, damped sine wave functions were
      fitted to the correlograms. Analysis of responses obtained from 202 recording
      sites showed that the vast majority of cells had become monocular. Auto
      correlation analysis revealed that the proportion of oscillatory firing patterns
      was similar to that observed in normal cats. However, cross-correlation analysis
      of 153 response pairs demonstrated that synchronization was reduced significantly
      between cells dominated by different eyes while it was as frequent and strong as
      in normal cats between cells dominated by the same eye. These findings indicate
      that strabismus not only causes a reorganization of afferent inputs but also
      affects intracortical interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261126
TI  - Functional organization of area V2 in the alert macaque.
AB  - We studied the relation between anatomical structure and functional properties of
      cells in area V2 of the macaque. Visual function was assessed in the alert animal
      during fixation of gaze. Recording sites were reconstructed with respect to
      cortical lamination and the cytochrome oxidase pattern. We measured orientation
      and direction selectivity, end-stopping, sensitivity to binocular disparity and
      ocular dominance, and determined more complex functions like sensitivity to
      anomalous contours and lines defined by coherent motion. Orientation selectivity
      was found in all parts of area V2, with high frequencies in the pale and thick
      stripes of the cytochrome oxidase pattern, and with lower frequency in the thin
      stripes. Representations of anomalous contours were found in the pale and thick
      stripes with similar frequencies, but generally not in the thin stripes, which
      have been thought to process colour. Lines defined by coherent motion were most
      frequently represented in the thick stripes; they were less frequent in the pale
      stripes, and (as with anomalous contours) were not found in the thin stripes.
      Sensitivity to binocular disparity was found in all types of stripes, but more
      frequently in the thick stripes, where the exclusively binocular neurons were
      also concentrated. By contrast, no segregation was found for direction
      selectivity and end-stopping. All neuronal properties were distributed evenly
      across cortical laminae. We conclude that mechanisms for figure-ground
      segregation involve the pale and the thick stripes of the cytochrome oxidase
      pattern, perhaps with greater emphasis on 'shape from motion' and 'stereoscopic
      depth' in the thick stripes, while more elementary neuronal properties are
      distributed almost evenly across the stripe pattern.

PMID- 8261127
TI  - Memory impairments following lesions to the mammillary region of the rat.
AB  - The contribution of the mammillary region to learning and memory was
      investigated. It was demonstrated that lesions of this region impair performance
      on tasks that require memory for spatial information but that the deficit depends
      both on the amount of damage within the region and the difficulty of the task. A
      dissociation in the effect of such lesions on performance of comparable spatial
      and non-spatial memory tasks was shown. In contrast to the deficits observed on
      spatial memory tasks, the acquisition and retention of a complex non-spatial
      memory task was not impaired after extensive damage to the mammillary region.
      Such lesions also did not impair performance in a conditioned taste aversion
      task. These experiments suggest that the mammillary region may be selectively
      involved in spatial learning and memory.

PMID- 8261128
TI  - Pharmacological and immunohistochemical evidence for serotonergic modulation of
      cholinergic nucleus basalis neurons.
AB  - Identified electrophysiologically by low threshold bursts and transient outward
      rectification, cholinergic nucleus basalis neurons were recorded and labelled
      intracellularly in guinea-pig basal forebrain slices. By means of a triple
      labelling immunofluorescent technique, serotonin-immunoreactive fibres were
      visualized in close proximity to the soma and dendrites of the biocytin-labelled,
      choline acetyl transferase (ChAT)-immunoreactive cells. By bath application, 5
      hydroxytryptamine (5-HT) produced a direct hyperpolarization of the identified
      cells which was mimicked by 5-HT1A receptor agonists, suggesting that it may
      inhibit the tonic firing but also modulate the low threshold bursting of the
      cholinergic nucleus basalis neurons.

PMID- 8261129
TI  - Sarcoplasmic calcium-binding proteins in Aplysia nerve and muscle cells.
AB  - Muscle (body wall, buccal mass, heart) and neural tissue of the marine mollusc
      Aplysia californica was analysed for calcium-binding proteins using
      transblot/45Ca overlay, Western blotting and two-dimensional polyacrylamide gel
      electrophoresis, and several low molecular weight calcium-binding proteins were
      identified. Our results that Aplysia muscle contains an abundant protein with a
      M(r) of approximately 20,000 with strong 45Ca(2+)-binding ability and cross
      reactivity to antibodies against the sarcoplasmic calcium-binding protein isoform
      II (SCP II) from Amphioxus. Immunocytochemical studies revealed that isoforms of
      SCP are distributed in a tissue-specific manner, SCP II-like protein is
      exclusively present in muscle fibres closely associated with the contractile
      machinery, whereas the isoform I (SCP I-like protein) is exclusively present in a
      subset of neurons, suggesting a function in their calcium regulation. In
      addition, a novel 45Ca(2+)-binding protein of M(r) 43,000, pl 4.7, was found in
      muscle and in neurons. A third protein of M(r) 40,000, pl 4.8, cross-reacts with
      anti-parvalbumin and anti-calbindin D-28K antibodies.

PMID- 8261130
TI  - Characterization of a calcium-dependent current generating a slow
      afterdepolarization of CA3 pyramidal cells in rat hippocampal slice cultures.
AB  - A depolarization-induced, slowly decaying inward current was examined in slice
      cultured CA3 pyramidal cells by voltage-clamp techniques and microfluorometric
      measurements of cytosolic free Ca2+ concentration ([Ca2+]i). Action potentials
      elicited by intracellular injection of short-lasting (50-100 ms) depolarizing
      current pulses were followed by a slowly decaying afterhyperpolarization (AHP).
      After switching to voltage-clamp mode, short-lasting (50-100 ms) depolarizing
      voltage jumps from -60 mV to between -30 and 0 mV induced a slowly decaying
      outward aftercurrent (IAHP) which was depressed by bath application of muscarine
      (0.5 microM). In the presence of muscarine, the same depolarizations induced a
      slowly decaying afterdepolarization (ADP) or inward aftercurrent (IADP) in
      voltage-clamp mode. This current was also induced in the presence of trans(+/-)-1
      amino-1,3-cyclopentanedicarboxylic acid (t-ACPD, 5 microM), an agonist of
      metabotropic glutamate receptors, but not in the presence of noradrenalin (5
      microM), while both of these agonists depressed IAHP. IADP was depressed by
      reducing the external Ca2+ concentration from 3.8 to 0.5 mM, by external Co2+ (1
      mM) and by external Cd2+ (10-100 microM). Combined voltage-clamp recordings and
      microfluorometric measurements of [Ca2+]i using the Ca2+ indicator fura-2
      revealed that the amplitude of IADP was correlated with the amplitude of
      depolarization-induced Ca2+ influx. IADP was absent at membrane potentials < -90
      mV, and reached maximal amplitudes at approximately -55 mV. Raising the
      extracellular K+ concentration from 2.7 to 13.5 mM increased the amplitude of
      IADP and resulted in a positively directed shift of the apparent reversal
      potential of IADP. When the external Na+ concentration was reduced from 157 to 33
      or 18 mM the current reversed at more negative potentials and was reduced to 40
      and 21%, respectively, of control amplitude. Lowering the external CI-
      concentration from 159 to 20 mM did not affect IADP. We conclude that IADP most
      likely represents a Ca(2+)-activated cation current, rather than a Ca2+ tail
      current, or an electrogenic Ca2+ extrusion current.

PMID- 8261131
TI  - Activity-dependent refinement of inhibitory connections.
AB  - Several lines of evidence suggest that excitatory synaptic transmission
      contributes to the maturation of precise neuronal connections. In the present
      study we determined whether the specific innervation pattern of single inhibitory
      arborizations was dependent upon neuronal activity during development. A
      homogeneous group of glycinergic inhibitory neurons in the central auditory
      system, the medial nucleus of the trapezoid body (MNTB), was functionally
      denervated in neonatal gerbils. The anatomical specificity of single MNTB
      terminal arborizations was subsequently measured along the tonotopic axis of a
      postsynaptic target, the lateral superior olive. Here we demonstrate that
      inhibitory terminal boutons spread a significantly greater distance along the
      frequency axis of the postsynaptic target following functional denervation.
      Although total arbor length remained unchanged, there was a significant increase
      in the number of branch points, suggesting de novo sprouting. The results
      indicate that normal inhibitory synaptic activity contributes to the
      developmental refinement of specific neuronal connections.

PMID- 8261132
TI  - Phosphoproteins of cultured cerebellar granule cells and response to the
      differentiation-promoting stimuli NMDA, high K+ and ionomycin.
AB  - In order to investigate signalling pathways involved in the control of granule
      cell differentiation, survival and other functions by depolarization or
      activation of NMDA receptors we have characterized protein phosphorylation in
      cerebellar granule cells. Cultures of cerebellar granule cells were incubated
      with 32P orthophosphate and then challenged with NMDA, K+ or the Ca2+ ionophore
      ionomycin, agents which raise [Ca2+]i and stimulate differentiation and survival.
      Upon separation of labelled phosphoproteins by two-dimensional gel
      electrophoresis three differences were found in response to all of these agents.
      These were an increase in acidity of two phosphoproteins of 87 and 48 kDa (p87
      and p48) and increased 32P-incorporation into a phosphoprotein of 120 kDa (p120).
      Treatment with PMA which stimulates neurite outgrowth but not survival affected
      p87 (increased its acidity) but not p48. The acidic shift of p87, therefore, is
      not sufficient to stimulate granule cell survival. The identification of p87 as
      the actin-binding MARCKS protein and the demonstration of its presence in
      neurites and growth cones of granule cells suggests that it may be involved in
      NMDA-stimulated neurite outgrowth. The phosphoproteins p120 and p48 may
      potentially be involved in events linking the rise in [Ca2+]i to increased
      granule cell survival or other aspects of granule cell differentiation.

PMID- 8261133
TI  - In vitro phosphorylation in isolated horizontal cells of the fish retina: effects
      of the state of light adaptation.
AB  - Horizontal cells, which are second-order neurons of the vertebrate retina,
      exhibit synaptic plasticity governed by light and dark adaptation. We have
      investigated the alterations in the protein phosphorylation patterns of isolated
      carp (Cyprinus carpio) horizontal cells in relation to their state of light
      adaptation by using an in vitro phosphorylation assay and compared the resulting
      data with protein synthesis patterns of the whole retina. Phosphoproteins and
      [35S]methionine-labelled proteins were analysed by one- and two-dimensional gel
      electrophoresis followed by autoradiography. The state of light adaptation
      significantly affected the in vitro phosphorylation of horizontal cell proteins
      with molecular weights of 68, 56/58, 47, 28 and 15 kDa, but had no effect on the
      protein synthesis of retinal proteins. In the light the most prominent increase
      of 32P incorporation was observed in the 47 kDa protein. The biochemical
      properties of this protein closely resembled those of the growth-associated GAP
      48, found in the fish retina. In addition, the phosphorylation of horizontal cell
      homogenates in the presence of protein kinase activators such as cyclic AMP,
      calcium, calmodulin and phospholipids revealed that horizontal cells of the fish
      retina contain cyclic AMP-, calcium/calmodulin- and calcium/phospholipid
      dependent protein kinase activity resulting in the phosphorylation of several
      horizontal cell proteins, including the phosphoproteins which were affected by
      the state of light adaptation.

PMID- 8261134
TI  - Negative regulation of Schwann cell myelin protein gene expression by the dorsal
      root ganglionic microenvironment.
AB  - In vivo, the surface glycoprotein Schwann cell myelin protein (SMP) is expressed
      in the quail peripheral nervous system exclusively by Schwann cells. It is not
      detectable at any developmental stage either in enteric glia or in ganglionic
      satellite cells. We demonstrate here that the satellite glial cells of the dorsal
      root ganglia start to express SMP on their surface when they are dissociated into
      single cells and cultivated in vitro. Activation of SMP synthesis is a rapid
      event observed in mass cultures of dorsal root ganglia dissociated cells as soon
      as 4 h after the onset of the culture. Confocal microscope analysis revealed that
      satellite cells may acquire the Schwann cell marker when still in close contact
      with the neuronal soma. Clonal cultures of satellite cells from E8 dorsal root
      ganglia demonstrated that the progeny of these SMP-negative cells steadily
      express SMP. This, together with similar results previously obtained with enteric
      glia, suggests that the SMP-positive phenotype is a constitutive trait of the
      peripheral glial cell lineage which is inhibited in satellite cells in vivo by
      the microenvironment prevailing in the peripheral nervous system ganglia.

PMID- 8261135
TI  - Widespread and developmentally regulated expression of neurotrophin-4 mRNA in rat
      brain and peripheral tissues.
AB  - The neurotrophin gene family includes four structurally related proteins with
      neurotrophic activities. Two of them, nerve growth factor and brain-derived
      neurotrophic factor (BDNF), have been studied in detail and information has
      recently emerged on the expression and function of the third member, neurotrophin
      3. In contrast, little information is available on neurotrophin-4 (NT-4), the
      most recently isolated member of this family. In this report we have used a
      sensitive RNAase protection assay to analyse the developmental expression of NT-4
      mRNA in the rat brain and in 12 different rat peripheral organs. In heart, liver
      and muscle plus skin NT-4 mRNA levels were maximal at embryonic day (E) E13 (the
      earliest time point tested), with reduced levels at later times of development.
      In lung, kidney and thymus similar levels were seen from E13 to postnatal day (P)
      1, with reduced levels in the adult. In testis, ovary and salivary gland NT-4
      mRNA was detected at E16 with a peak shortly after birth. During brain
      development, NT-4 mRNA was maximal at E13 followed by a decrease around birth,
      after which the level increased. The postnatal increase of NT-4 mRNA was also
      seen in cerebral cortex and brain stem analysed separately, while in the
      hippocampus similar levels were found from P1 to adulthood. NT-4 mRNA was
      detected in all ten adult rat brain regions analysed with only small regional
      variations, being highest in pons-medulla, hypothalamus, thalamus and
      cerebellum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261136
TI  - An abundant mRNA of the embryonic brain persists at a high level in cerebellum,
      hippocampus and olfactory bulb during adulthood.
AB  - In order to identify markers of the two neuronal populations which are
      successively involved in forebrain ontogenesis, we performed a differential
      screening of a murine cDNA library with two radiolabelled probes corresponding to
      striatal mRNAs extracted at embryonic day (E) 17 and E20, i.e. before and after
      the invasion of the striatum by the late-born matrix neurons. One of the selected
      clones, the 3.1 cDNA, corresponds to a very abundant embryonic neuronal
      transcript enriched in the germinal zones at E17 and in superficial cortical
      layers and striatum at E20, suggesting that it is expressed mainly in neurons
      belonging to a late migration wave. During adulthood, it persists at a high level
      in the granular layer of the cerebellum, the hippocampus and the olfactory bulb,
      which are the sites of postnatal neurogenesis and intense synaptic plasticity.
      This 2000 base RNA is enriched in polysomal fractions and encodes a small
      putative 68 amino acid polypeptide which is conserved in mouse and man.

PMID- 8261137
TI  - Urokinase-type plasminogen activator expression by neurons and oligodendrocytes
      during process outgrowth in developing rat brain.
AB  - The expression of tissue- and urokinase-type plasminogen activators has been
      studied in developing cerebellum, hippocampus, cerebral cortex, olfactory bulb
      and olfactory mucosa of the rat by in situ hybridization. All identifiable
      neurons express urokinase mRNA from an early stage in their development, and this
      expression appears to coincide with the onset of axogenesis. For cerebellar
      granule cells, both axonal growth and urokinase expression are initiated before
      they migrate from the external granule layer; for the majority of neocortical
      neurons, however, both processes are commenced after the cells have migrated to
      the cortical plate. Neurons continue to express this protease in the adult. The
      large projection neurons exhibit the highest levels of message, the smaller
      interneurons having much lower levels except for hippocampal granule cells, which
      have notably high levels of expression. Glial cells generally do not express
      urokinase message, except for transient expression by oligodendrocytes in
      developing fibre tracts during the period of myelination. Thus for both neurons
      and oligodendrocytes, the onset of urokinase-type plasminogen activator
      expression coincides with their initiation of major process outgrowth, although
      neurons maintain this expression in the adult, possibly to retain a degree of
      synaptic plasticity. In contrast, although high levels of message for the related
      protease, tissue plasminogen activator, are found in the embryonic floor plate,
      in postnatal brain it is abundantly expressed only by ventricular ependymal cells
      and by cells in connective tissue surrounding the olfactory nerve.

PMID- 8261138
TI  - Developmentally regulated expression of CGRP in the mouse olfactory pathway.
AB  - The pattern of expression of the neuropeptide CGRP and its encoding mRNA has been
      determined by immunohistochemistry and in situ hybridization in the mouse
      olfactory pathway during development. Specific CGRP transcripts are first
      detected at E13 followed by the appearance of the peptide at E15. Both peptide
      and transcript are present until birth; their expression then appears to be down
      regulated since postnatally the peptide is only observed in some olfactory
      receptor neurons. A monoclonal antibody that specifically recognizes the
      neurofilament subunit NF-M has been used in order to identify olfactory and
      trigeminal axons. Our results demonstrate that CGRP is expressed in olfactory
      neurons and their axons during development, thus supporting further its role as a
      differentiation factor during olfactory bulb ontogenesis.

PMID- 8261139
TI  - Spatiotemporal distribution of Ca2+ following axotomy and throughout the recovery
      process of cultured Aplysia neurons.
AB  - This study investigates the alterations in the spatiotemporal distribution
      pattern of the free intracellular Ca2+ concentration ([Ca2+]i) during axotomy and
      throughout the recovery process of cultured Aplysia neurons, and correlates these
      alterations with changes in the neurons input resistance and trans-membrane
      potential. For the experiments, the axons were transected while imaging the
      changes in [Ca2+]i with fura-2, and monitoring the neurons' resting potential and
      input resistance (Ri) with an intracellular microelectrode inserted into the cell
      body. The alterations in the spatiotemporal distribution pattern of [Ca2+]i were
      essentially the same in the proximal and the distal segments, and occurred in two
      distinct steps: concomitantly with the rupturing of the axolemma, as evidenced by
      membrane depolarization and a decrease in the input resistance, [Ca2+]i increased
      from resting levels of 0.05-0.1 microM to 1-1.5 microM along the entire axon.
      This is followed by a slower process in which a [Ca2+]i front propagates at a
      rate of 11-16 microns/s from the point of transection towards the intact ends,
      elevating [Ca2+]i to 3-18 microM. Following the resealing of the cut end 0.5-2
      min post-axotomy, [Ca2+]i recovers in a typical pattern of a retreating front,
      travelling from the intact ends towards the cut regions. The [Ca2+]i recovers to
      the control level 7-10 min post-axotomy. In Ca(2+)-free artificial sea water (2.5
      mM EGTA) axotomy does not lead to increased [Ca2+]i and a membrane seal is not
      formed over the cut end. Upon reperfusion with normal artificial sea water,
      [Ca2+]i is elevated at the tip of the cut axon and a membrane seal is formed.
      This experiment, together with the observations that injections of Ca2+, Mg2+ and
      Na+ into intact axons do not induce the release of Ca2+ from intracellular
      stores, indicates that Ca2+ influx through voltage gated Ca2+ channels and
      through the cut end are the primary sources of [Ca2+]i following axotomy.
      However, examination of the spatiotemporal distribution pattern of [Ca2+]i
      following axotomy and during the recovery process indicates that diffusion is not
      the dominating process in shaping the [Ca2+]i gradients. Other Ca2+ regulatory
      mechanisms seem to be very effective in limiting these gradients, thus enabling
      the neuron to survive the injury.

PMID- 8261140
TI  - Recovery of brightness discrimination in adult rats despite progressive loss of
      retrogradely labelled retinal ganglion cells after controlled optic nerve crush.
AB  - Restoration of brightness discrimination was studied in adult rats after
      controlled crush of the optic nerve in order to further characterize a recently
      introduced experimental brain injury model. Mild, moderate or severe crush of the
      optic nerve produced partial or complete loss of the ability to perform a
      brightness discrimination task. Two to three weeks following mild injury we
      observed nearly complete spontaneous behavioural recovery whereas recovery was
      more limited after moderate and totally absent after severe crush. Horseradish
      peroxidase (HRP) injected into the superior colliculus was transported
      retrogradely across the lesion site and accumulated in retinal ganglion cells
      (RGCs). Two days following mild, moderate or severe crush, 28, 23 and 8%
      respectively of RGCs were found to be labelled with HRP, indicating that they are
      still connected with their target and are therefore presumably intact. RGC loss
      affected all areas of the retina homogeneously. At postoperative day 14, the
      number of morphologically 'intact' RGCs declined even further to 11% in the mild
      injury group, despite our observation of recovery of vision to near-normal
      levels. The mechanism whereby such impressive neuronal plasticity is achieved
      despite the rather small number of intact RGCs is still unknown. However, further
      studies of the crush model using additional behavioural, morphological and
      electrophysiological techniques may allow us to determine more clearly the
      biological basis of recovery of function after central nervous system injury.

PMID- 8261141
TI  - The mode of activation of a barrel column: response properties of single units in
      the somatosensory cortex of the mouse upon whisker deflection.
AB  - Response properties of single units in the mouse barrel cortex were studied to
      determine the sequence in which the neurons that form a cortical column become
      activated by a single 'natural' stimulus. Mice (n = 11) were anaesthetized with
      urethane. For a total of 153 cells, grouped by cortical layer, responses to a
      standardized deflection of a single whisker were characterized using poststimulus
      time and latency histograms. Usually, for each unit, data were collected for
      stimulation of its principal whisker (PW; the whiskers corresponding to the
      barrel column in which the cell was located) and of the four whiskers surrounding
      the PW. In all layers, PW stimulation evoked responses at shorter latency than
      surround whisker stimulation. In layers II-III and IV a bimodal distribution of
      cells according to latency to PW stimulation was found. Statistical analysis
      indicated the presence of two classes of cells in each of these layers: 'fast'
      units (latency < 15 ms) and 'slow' units (latency > or = 15 ms). The great
      majority of cells in layers I, V and VI fired at latencies of > 20 ms to PW
      stimulation. In general, stimulation of surround whiskers evoked a smaller
      response than PW stimulation. The fast cells of layer IV showed the greatest
      response to PW stimulation (mean = 1.78 spikes/100 ms poststimulus). Their firing
      was maximal during the 10-20 ms poststimulus epoch, while the slow layer IV cells
      fired maximally during the 20-30 ms poststimulus epoch. Surround inhibition
      occurred in all layers within the first 10 ms after stimulus onset, during which
      period the fast cells are the most active ones, and are thus likely to be
      responsible for the surround inhibition. This notion is supported by an analysis
      of spike duration that showed that eight of the ten cells with a thin spike
      (supposed to be GABAergic; McCormick et al., J. Neurophysiol., 54, 782-806,
      1985), had PW latencies of < 15 ms. We conclude that the activation of a barrel
      column is initially inhibitory in nature.

PMID- 8261142
TI  - Changes in the mechanical tuning characteristics of the hearing organ following
      acoustic overstimulation.
AB  - An in vitro preparation of the guinea-pig temporal bone was used to study the
      effects of acoustic overstimulation on the mechanical tuning characteristics of
      the inner ear. Using laser heterodyne interferometry, the vibratory responses of
      selected sensory and supporting cells within the hearing organ were measured in
      response to acoustic signals applied to the ear to obtain mechanical tuning
      curves before and after applying acoustic overstimulation. Following
      overstimulation the frequency at which the maximal vibration response occurred
      moved towards lower frequencies, the vibration amplitude generally increased and
      the shape of the mechanical tuning curves became considerably flatter. These
      effects were seen within minutes of overstimulation. The micromechanical changes
      were accompanied by distinct morphological changes mainly affecting the first row
      of outer hair cells, which were swollen and shortened. Hensen bodies and swelling
      of the subsurface cisternae were observed in the affected cells. Apart from this,
      most of the shortened cells looked structurally intact, had undamaged sensory
      hair bundles and made synaptic contacts to both afferent and efferent nerve
      fibres. The results demonstrate that the outer hair cells play a key role in
      determining the tuning of the hearing organ.

PMID- 8261143
TI  - Functional organization of the human first and second somatosensory cortices: a
      neuromagnetic study.
AB  - Multichannel neuromagnetic recordings were used to differentiate signals from the
      human first (SI) and second (SII) somatosensory cortices and to define
      representations of body surface in them. The responses from contralateral SI,
      peaking at 20-40 ms, arose mainly from area 3b, where representations of the leg,
      hand, fingers, lips and tongue agreed with earlier animal studies and with
      neurosurgical stimulations and recordings on convexial cortex in man.
      Representations of the five fingers were limited to a cortical strip of
      approximately 2 cm in length. Responses from SII peaked 100-140 ms after contra-
      and ipsilateral stimuli and varied considerably from one subject to another.
      Signs of somatotopical organization were seen also in SII. Responses of SII were
      not fully recovered at interstimulus intervals of 8 s.

PMID- 8261144
TI  - Differential responses of single reticulospinal cells to spatially localized
      stimulation of the optic tectum in a teleost fish, Salmo trutta.
AB  - To determine whether the topographically organized retinal input to the optic
      tectum is subsequently mapped onto the reticular formation, the responses of
      antidromically identified reticulospinal cells to tectal surface stimulation were
      investigated in 45 decerebrated, paralysed trout. The tectum was stimulated
      through a silver ball surface electrode at 24 different locations, and
      extracellular recordings were made from the rhombencephalic brainstem with glass
      microelectrodes filled with a 10% solution of horseradish peroxidase (HRP) in
      Tris buffer (pH 7.4). After recording, the HRP was, in some cases,
      iontophoretically expelled from the pipette to identify its location and
      visualized in histological sections by a modified Hanker-Yates method. Individual
      reticulospinal neurons discharged 1-4 spikes at short latency in response to
      stimulation of each of the 24 tectal locations. From one tectal location per
      cell, this initial response was followed by a late, sustained burst. With a short
      stimulus train (6 pulses, 55 Hz) the burst could last for over a second with
      discharge rates of up to 500 Hz. Sometimes this burst could be evoked from
      neighbouring tectal locations, but only by greatly increasing the stimulus
      strength. We conclude that the reticular formation receives a highly divergent
      monosynaptic connection from all locations of the tectum and that the longer
      latency, sustained burst response is due to a mapped connection between the
      tectum and the reticular formation. Since the late burst could be preceded by a
      silent period lasting for approximately 32 ms, we cannot rule out a dependence on
      interneurons situated between the tectum and the reticulospinal cells.

PMID- 8261145
TI  - Expression of c-Jun as a response to dorsal root and peripheral nerve section in
      damaged and adjacent intact primary sensory neurons in the rat.
AB  - It was previously shown that the immediate early gene, c-jun, was highly
      expressed over long periods, in both peripheral sensory and motor neurons
      following axon damage or block of axoplasmic transport. Here we have examined the
      question of whether the expression of c-Jun protein is related to axon injury per
      se or to the process of axon growth. We have examined dorsal root ganglion (DRG)
      cells subjected to different manipulations which are associated with varying
      degrees of regrowth, as follows: (i) after peripheral nerve section, where it
      appears that all damaged neurons make some regenerative effort. 1-24 days after
      sciatic nerve section and ligation most cells in L4/L5 DRG were c-Jun-positive;
      (ii) after section of the central processes of the DRG cells, which then showed a
      slow and limited regrowth of their axons towards, but not into, the spinal cord.
      This resulted in a variable, but significant, expression of c-Jun in a small
      number of DRG cells; (iii) in intact sensory neurons that were offered the
      opportunity to sprout into adjacent denervated peripheral tissue. The sciatic
      nerve was ligated and the response of cells in the L3 ganglia (many of which
      project to the saphenous nerve) was measured. A small but significant number of
      cells were c-Jun-positive; (iv) in intact sensory neurons that were offered the
      opportunity to sprout centrally into partialy denervated neuropil of the spinal
      cord. We examined neurons in the L3 DRG after rhizotomy of the adjacent L4/L5
      dorsal roots. Previous work suggests that sensory neurons show at best a very
      limited growth under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261146
TI  - Positive and negative brain zones in the snail.
AB  - Fine wire electrodes were surgically implanted in two regions of the brain of the
      snail Helix aspersa. To receive electrical stimulation of the brain, a tethered
      snail was required to displace the end of a rod. Self-stimulation delivered to
      the parietal ganglion resulted in non-repetition of the operant response, whereas
      self-stimulation delivered to the mesocerebrum resulted in an increase in
      response frequency. The reinforcing effect of local extracellular stimulation of
      two brain zones was investigated in a semi-intact preparation of a closely
      related species with an identical cellular map (H. lucorum). It was found that
      mesocerebral stimulation increased the frequency of the reinforced spontaneous
      movement, but decreased the frequency of the same movement if its absence was
      reinforced. These results allow us to attribute positive reinforcing effects to
      this brain area, which is involved in the control of sexual behaviour. Different
      results were obtained by contingent stimulation of the rostral part of the
      parietal ganglia, where giant cells controlling avoidance behaviour are located.
      Stimulation of this zone resulted in a decrease in the frequency of the ongoing
      spontaneous movements. These findings make possible intracellular investigations
      of the mechanisms of positive and negative reinforcement.

PMID- 8261147
TI  - Mitral homograft for tricuspid valve replacement.

PMID- 8261148
TI  - Tricuspid valve replacement using a mitral homograft. Surgical technique and
      initial results.
AB  - Tricuspid valve replacement using a cryopreserved mitral valve homograft was
      carried out with success in three HIV positive drug addicts suffering from fungal
      or bacterial endocarditis. All three patients are alive and symptomless up to 16
      months after surgery. This procedure is considered to be an alternative to other
      methods of tricuspid valve replacement if repair is not feasible. Further
      experience is needed to assess the long term performances of mitral homografts in
      the tricuspid position.

PMID- 8261149
TI  - Surgical treatment of intractable right-sided infective endocarditis in drug
      addicts: 25 years experience.
AB  - During the past 25 years the authors have performed the following operations in
      the surgical treatment of intractable right-sided endocarditis in drug addicted
      patients: 1) Excision of the infected tricuspid valve and replacement with a
      mechanical or bioprosthetic valve during the same operation. In these patients
      the overall mortality was 100% due to: (a) inability to control the endocarditis
      in 80%; (b) re-infection due to a return to drug abuse and (c) fatal
      complications due to non-compliance with anticoagulant therapy. 2) Tricuspid
      valvulectomy in 53 patients, tricuspid and pulmonary valvulectomy without
      replacement in two patients. Six patients (11%) died within six weeks. Five due
      to the endocarditis and one due to low cardiac output. Ten patients (18%) died
      six months to 13 years later. In nine of these patients, death was related to
      continued drug abuse. At 22 years the actuarial survival is 64%. This experience
      supports the authors conclusion that among drug addicts with intractable right
      sided endocarditis, tricuspid valvulectomy or tricuspid and pulmonary
      valvulectomy without replacement is/are the operation(s) of choice.

PMID- 8261150
TI  - Endocarditis in intravenous drug addicts and HIV infected patients: possibilities
      and limitations of surgical treatment.
AB  - The incidence of infective endocarditis in drug addicts is increasing with the
      spread of intravenous drug abuse. The tricuspid valve is involved most commonly,
      followed by the mitral. We evaluated 22 patients prospectively with a mean age of
      23 years, presenting with addiction-associated endocarditis and referred to our
      institution during a three-year period. The tricuspid valve was involved in 13
      instances, the mitral in four, mitral plus tricuspid valves in five patients and
      the aortic valve in one. Staphylococcus aureus was the most frequent infective
      organism (15 cases), followed by streptococci (4 cases), corynebacteria (2 cases)
      and one case with a mixed infection. Six patients were HIV positive and 17 had
      evidence of chronic viral hepatitis. Ten patients (three of them HIV positive)
      were treated surgically. Resection of the tricuspid valve with (one case) or
      without replacement (four cases), resection of vegetations and tricuspid repair
      (two cases), mitral valve replacement (2 cases) and aortic valve replacement (one
      case) were performed. Operative mortality (< 30 days) was high (2/10, 20%); one
      patient died from cerebral hemorrhage and another from multi-organ failure.
      Another three patients died after a mean follow up of 10 months. In 12 patients,
      surgery was not attempted because of still existing intravenous drug abuse or
      renal and liver failure. Five of these patients died after a mean follow up of 13
      months, two from septicemia, two from AIDS-related complications and one from
      drug overdose. The prognosis of drug-associated endocarditis treated with
      antibiotics is generally good.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261151
TI  - Preservation of the tensor apparatus of the mitral valve.

PMID- 8261152
TI  - The effect of chordal preservation on late outcome after mitral valve
      replacement: a randomized study.
AB  - Postoperative survival, hemodynamic status and exercise tolerance with or without
      posterior chordal preservation were compared in a case-limited prospective
      randomized manner in 100 patients who underwent isolated mitral valve replacement
      with size 29mm or 31mm St. Jude Medical prostheses. The preoperative clinical and
      hemodynamic parameters were comparable in the two groups. The mean follow up was
      293.3 months for those with and 263.1 months for patients without chordal
      preservation. Right heart cardiac catheterization was performed in every patients
      at the end of the follow up period and it demonstrated significantly better
      results with than without chordal preservation (cardiac index 2.81 +/- 0.47 vs.
      2.63 +/- 0.52, p < 0.05; pulmonary arterial pressure 30 +/- 11 mmHg vs. 37 +/- 13
      mmHg at 30 Watts bicycle exercise, p < 0.01; end-diastolic volume index 75 +/- 22
      vs. 86 +/- 38 ml/m2, p < 0.02; and maximum exercise tolerance 1.8 +/- 0.3 vs. 1.2
      +/- 0.5 Watt/kg, p < 0.01). Actuarial freedom from complications was 78.1 +/-
      4.2% with and 70.7 +/- 6.2% without chordal preservation (p < 0.02). In
      particular, patients with severe mitral regurgitation benefited from the
      preservation of the posterior mitral leaflet with its chordal and papillary
      structure (p < 0.001).

PMID- 8261153
TI  - Comparative evaluation of left ventricular performance after mitral valve repair
      or valve replacement with or without chordal preservation.
AB  - The clinical importance of preserving the chordae tendineae during mitral valve
      replacement was assessed by comparing the postoperative left ventricular
      performances in 68 patients who underwent mitral valve replacement (MVR) with
      complete chordal preservation (n = 19), conventional MVR (n = 25) or mitral valve
      repair (n = 24) and had full hemodynamic assessment before and after surgery. The
      pre- and postoperative left ventricular performances were analyzed using
      cineangiography, multiple-gated cardiac blood pool scintigraphy (MUGA), and
      echocardiography. In the early postoperative period, cineangiography revealed
      that the end-systolic volume index (ESVI) and the end-diastolic pressure were
      significantly higher in the conventional MVR group. The left ventricular ejection
      fraction was unchanged in the chordal preservation group, but was decreased in
      the mitral repair and conventional MVR groups. The end-systolic circumferential
      left ventricular wall stress (ESS) was significantly decreased in the chordal
      preservation and mitral repair groups, but was unchanged, and thus higher, in the
      conventional MVR group. The postoperative left ventricular contractility index
      (ESS/ESVI) was better in the chordal preservation than in the conventional MVR
      group. In the late postoperative period, both the left ventricular ejection
      fraction as measured by MUGA and the left ventricular fractional shortening as
      measured by echocardiography were significantly higher in the mitral repair and
      chordal preservation groups than in the conventional MVR group. This study
      supports the concept that the maintenance of continuity between the mitral
      annulus and the papillary muscles has a beneficial effect on postoperative left
      ventricular performance.

PMID- 8261154
TI  - A new Doppler method for assessing left ventricular diastolic stiffness based on
      principles of flow wave propagation: mathematical basis and review of the method.
AB  - Color flow imaging shows that the transmitral flow is initially directed to the
      left ventricular (LV) apex and then turns around facing the aortic valve. A
      pulsed wave Doppler sample placed in the LV outflow tract (LVOT) records two
      peaks of diastolic flow waves, Er and Ar waves, which follow E and A waves of the
      transmitral flow respectively. The Er and Ar waves represent transmitted E and A
      flow waves to the LVOT. Our preliminary clinical and hemodynamic data in human
      subjects have shown that the A-Ar interval, which is the time taken for the A
      velocity wave to propagate from the mitral valve to the LVOT, is shorter in those
      with LV hypertrophy (LVH), the aged and those with elevated LV late diastolic
      stiffness, suggesting faster A wave transmission in those with stiffer
      ventricles. We also have shown that velocity and pressure waves propagate
      similarly in the arterial system. This led to the hypothesis that the A wave
      transmission inside the LV may follow the principles described in the Moens
      Korteweg equation, or a modification of it, and the velocity of A wave
      transmission inside the LV may reflect its late diastolic stiffness. Studies
      designed to test this hypothesis in a pulsatile LV model showed a linear
      relationship between the rate of diastolic flow wave propagation inside the LV
      and its stiffness. These preliminary data suggest that the velocity of A wave
      transmission inside the LV reflects LV late diastolic stiffness non-invasively.
      It is expected to be independent of a direct effect of heart rate and of preload.

PMID- 8261155
TI  - Doppler analysis of portal vein flow in tricuspid regurgitation.
AB  - Portal and hepatic vein flow-velocity profiles were examined by pulsed Doppler in
      66 patients with tricuspid regurgitation (color Doppler grading: severe: 37,
      moderate: 18; mild: 11) and 20 normal subjects to determine if portal vein flow
      analysis is useful in the evaluation of tricuspid regurgitation. Portal vein flow
      was defined as one of the following categories: subcontinuous (dependent on
      respiration), pulsatile systolic (not inverted), inverted after systole, and
      continuous (not dependent on respiration). An index of portal vein flow
      pulsatility was also calculated. Standard classification of hepatic vein flow
      pattern was performed. Portal vein flow was pulsatile in 20% of normals subjects,
      and in 27.3% 44.5% and 51.3% of patients with respectively mild, moderate and
      severe tricuspid regurgitation; portal vein flow was inverted after systole in
      further 32.4% of patients with severe tricuspid regurgitation. Portal vein
      pulsatility index correlated with color Doppler grading of tricuspid
      regurgitation (r:0.63; p < 0.001) and right ventricle-atrium pressure gradient
      (r:0.39; p < 0.01). However, when compared with hepatic vein flow, both
      sensitivity and specificity of quantitative portal vein flow analysis was less
      reliable in diagnosing and grading tricuspid regurgitation. In particular, in
      patients with severe tricuspid regurgitation, the portal vein flow pattern was
      quite variable (pulsatile in 19 patients, inverted after systole in 12, and
      continuous in six). Liver biopsy was performed in nine patients, four of them
      with severe tricuspid regurgitation and continuous portal vein flow. Histology
      showed severe liver fibrosis in all four.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261156
TI  - Assessment of prosthetic valve hemodynamics by Doppler: lessons from in vitro
      studies of the St. Jude valve.
AB  - Although Doppler assessment of native heart valve hemodynamics is quite accurate,
      assessment of prosthetic mechanical valve hemodynamics presents more potential
      problems. These problems arise from the unique geometry of prosthetic valves. Two
      important prosthetic valve phenomena can violate the basic assumptions underlying
      Doppler calculations: pressure recovery and localized gradients. When pressure
      recovery is present, Doppler systematically overestimates the actual net catheter
      gradient across the valve. In contrast, the presence of localized gradients may
      cause Doppler to measure differing gradients depending on which part of the valve
      is interrogated. These phenomena can also affect the calculation of prosthetic
      valve areas using the continuity equation. When assessing prosthetic valves with
      Doppler echocardiography, it must be remembered that Doppler measures velocity,
      not pressure gradients and that the echocardiographer must exercise great care
      when interpreting Doppler velocities as either pressure gradients or in
      calculating valve areas for prosthetic valves.

PMID- 8261157
TI  - The challenge of valve surgery in a developing population.
AB  - Between August 1988 and October 1992, 1,052 patients underwent 1,522 valve
      procedures in our institution. Their mean age was 32.69 years (range 1-90). The
      etiology was rheumatic in 724 (68.8%), congenital in 120 (11.4%), degenerative in
      99 (9.4%), infective in 58 (5.5%) and ischemic in 17 (1.6%). The mean
      preoperative functional class (NYHA) was 2.95 and 780 (74.1%) were in sinus
      rhythm. Repair was possible in 885 (58.1%) valves. The rate of repair versus
      replacement was 94.5% for the tricuspid, 56.2% for the mitral and 43.6% for the
      aortic valve. The total hospital mortality was 4.18%. For isolated mitral surgery
      it was 2.94%, for isolated aortic 4.12% and for isolated tricuspid 15%. Double
      valve surgery carried a mortality of 3% and triple valve surgery 13%. Hospital
      mortality for isolated mitral and isolated aortic surgery was lower for repair
      than for replacement (1.5% vs. 5% and 0 vs. 6.8%). The follow-up was 94.65%
      complete. The total incidence of embolic events was 2.93% with an actuarial
      freedom at 48 months of 92.71 +/- 5.35% for repair, 88.22 +/- 6.26% for
      replacement and 90.31 +/- 5.65% for patients with repair and replacement. Late
      mortality was 4.5%. The actuarial survival excluding hospital deaths was 94.89 +/
      2.10% for repair, 86.84 +/- 2.84% for replacement and 91.33 +/- 2.73% for the
      mixed group. The reoperation rate was higher for repair (13%) than for
      replacement (0.1%). This rate was highest for the rheumatic mitral patients with
      an age below 20 years (25.2%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261158
TI  - Influence of isosorbide dinitrate (ISDN) on compliance of the pulmonary venous
      system.
AB  - Irreversible poor pulmonary venous compliance can worsen the natural course of
      patients with high pulmonary capillary wedge pressure, especially those with
      mitral stenosis, but nitrates (isosorbide dinitrate--ISDN), which have
      venodilatory properties, could increase this compliance in most patients. The aim
      of this study was to assess the hemodynamic effects of ISDN in patients with
      mitral stenosis, with special emphasis on the pulmonary venous compliance.
      Pulmonary venous compliance was estimated according to the Hirakawa equation
      (dV/dp = 0.4 x k2 x sV/(v-d)) in 39 patients with mitral stenosis during
      preoperative right heart catheterization with Vygon 5155-180 thermodilution
      catheters at rest and during exercise (25 W) in the supine position. This
      procedure was repeated after the application of 3.75 mg of Iso-Mack spray.
      Overall, ISDN increased pulmonary venous compliance significantly both at rest
      and during exercise (6.0 to 7.5 ml/mmHg and 6.0 to 7.6 ml/mmHg, respectively).
      The patients were divided into two groups according to their level of ISDN
      response; those with a good response of an increase of 15% or more in pulmonary
      venous compliance (Group I), and those with an increase of less than 15% (Group
      II). There were significant differences between these two groups in stroke volume
      index and heart rate. In Group I, while the mean right atrial pressure, mean
      pulmonary artery pressure and mean pulmonary wedge pressure all decreased
      significantly, there was a simultaneous insignificant decrease in the stroke
      volume index and an also insignificant increase in the heart rate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8261159
TI  - The chest radiograph in adult heart valve disease.

PMID- 8261160
TI  - Complex balloon mitral valvuloplasty.
AB  - With increasing operator experience, balloon mitral valvuloplasty, like complex
      coronary angioplasty, has been successfully attempted on patients with mitral
      stenosis complicated by a variety of factors, including severe pulmonary
      hypertension, tricuspid regurgitation, poor ventricular function, previous
      commissurotomy, extremes of age and suboptimal valve anatomy. Only this latter
      factor should be considered a major deterrent to BMV, at least in hospitals where
      the technique has been acquired and where balloon catheters are affordable.

PMID- 8261161
TI  - Optimal timing of surgery for chronic mitral or aortic regurgitation.
AB  - Symptoms tend to develop late in the course of both chronic mitral and chronic
      aortic regurgitation, and when the regurgitation is stable patients may enjoy
      many years of full activity free from disability. In the absence of complicating
      atrial fibrillation or coronary artery disease the onset of dyspnoe and fatigue
      usually indicate myocardial failure and possibly a lost opportunity for a low
      risk operation and long term benefit. Valve replacement for aortic regurgitation
      is a good operation which reduces left ventricular work. However, mitral valve
      replacement is unphysiologic and not surprisingly, the operative mortality and
      long term results are worse with an excess of deaths caused by left ventricular
      failure. While the need for operation is obvious when patients already have
      symptoms or when valvar regurgitation is increasing, timing is far more difficult
      for patients with severe, chronic, stable regurgitation who still enjoy a high
      quality of life. It is even more difficult in mitral regurgitation because the
      stakes are higher with a higher operative risk, but suitability for mitral valve
      reconstruction justifies earlier operation and therefore makes it mandatory for
      cardiologists to identify such patients.

PMID- 8261162
TI  - Differential collagen distribution in the mitral valve and its influence on
      biomechanical behaviour.
AB  - Surgical repair of the mitral valve primarily involves endogenous valve tissue,
      however, the intrinsic mechanical behaviour of the tissue is not well described.
      To address this issue, porcine mitral valve leaflets were examined histologically
      and engineering concepts were applied to understand the mechanical behaviour of
      the layered tissue. Rectangular portions were excised from the anterior and
      posterior leaflets, either parallel or perpendicular to the annulus, and sections
      were stained for collagen (Masson's trichrome). The cross sectional layers of the
      valve (atrialis/spongiosa, fibrosa, and ventricularis) were identified by
      differences in cellularity and collagen density. The fibrosa is composed of dense
      collagen, while the atrialis/spongiosa and ventricularis are composed of loose
      collagen. Layer thicknesses were recorded digitally across the section. These
      values were averaged within tissue groups to determine changes in layer thickness
      over the length of the sample and average thickness of each layer. In all tissue
      groups, the fibrosa was the thickest layer, and the atrialis/spongiosa layer was
      thicker than the ventricularis layer. The total and fibrosa layer thicknesses of
      the anterior leaflet were significantly thicker than in the posterior leaflet.
      Mechanical engineering analysis of the layered structures under tension indicated
      that the anterior leaflet would be able to support greater tensile loads than the
      posterior leaflet. The layered arrangement was then examined as a beam in
      bending, and was shown to decrease the resistance of leaflets to bending, and
      decrease the overall bending stresses on the leaflet. This type of analysis may
      be extrapolated to gain insight into changes in function in diseased valves as
      well.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261164
TI  - In response to: Grunkemeier GL, Starr A. Alternatives to randomization in
      surgical studies.

PMID- 8261163
TI  - Ball fracture with the 6120-model Starr-Edwards mitral valve prosthesis occurring
      late after implantation.
AB  - The Starr-Edwards (S-E) mitral valve, Model 6120, has been widely used in the
      last three decades. Fatty infiltration and subsequent damage of the silastic
      ball, a phenomenon termed ball variance, has been described only in the first
      generation aortic ball-valve prostheses, used until 1965. A case of partial ball
      fracture in a 6120-Model S-E mitral valve prosthesis, occurring 27 years after
      implantation and presenting with thromboembolism and progressive valve
      dysfunction, is described.

PMID- 8261165
TI  - In response to: Donald N. Ross. Left ventricular outflow tract: some lessons
      learned.

PMID- 8261166
TI  - Synergistic toxicity of IFN-gamma-producing Escherichia coli K12 cells.
AB  - Genetically modified microorganisms (GMMs) are frequently used as producers of
      mammalian immunomodulatory proteins, e.g. interferons and interleukins. Here we
      have examined the question of whether such GMMs interact in a way different from
      that of their non-modified parent micro-organisms with mammalian antimicrobial
      defence systems. As a typical GMM host micro-organism we used Escherichia coli
      K12, and as a typical immunomodulatory protein produced by a GMM we used mouse
      interferon-gamma (MuIFN-gamma). Two experimental systems are described in which
      synergistic "toxic" biological effects are induced by a combined treatment with
      E. coli and MuIFN-gamma but not, or less so, by the parental strain and the
      recombinant protein separately. First, it is shown that the IFN-gamma-producing
      GMM, or mixtures of E. coli cells and IFN-gamma, are cytolytic for mouse embryo
      fibroblastoid cells (MEF), whereas no cell killing occurs in MEF cultures treated
      with control E. coli cells or in those treated with bacteria-free recombinant IFN
      gamma. Second, it is demonstrated that intraperitoneal injection in mice of high
      but not low numbers of control E. coli K12 cells induces a shock-like mortality,
      whereas co-injection with IFN-gamma induces killing at low numbers. IFN-gamma
      producing E. coli cells cause a mortality rate that does not differ from that of
      control E. coli cells, probably because in these experimental conditions the
      level of recombinant MuIFN-gamma per cell is insufficiently high. Taken together,
      these data indicate that synergistic toxic effects induced by bacteria and their
      recombinant products can occur and may in certain situations enhance the
      intrinsic toxic capacity of the GMM. Synergistic toxic effects may thus be of
      relevance for identifying the safety level that should be employed when working
      with GMMs.

PMID- 8261167
TI  - Rapid method for purification of soil DNA for hybridization and PCR analysis.
AB  - Monitoring of microbial DNA in soils by dot blot hybridization and PCR analysis
      is a useful technique for gaining insight into the survival and impact of
      genetically modified micro-organisms released in the environment. Most methods of
      DNA isolation from soils require a large number of purification steps rendering
      them unsuitable for quantitative analysis of multiple samples. Here we describe a
      very rapid method for the isolation and purification of multiple samples of soil
      DNA that can be used directly for dot blot hybridization and PCR analysis. Soil
      DNA extracts are prepared by lysozyme/SDS treatment at pH 9.0 and purified by
      ammonium acetate precipitation and Sephadex G50 gel filtration. In a practical
      application of this method, sandy soil samples were seeded with Alcaligenes
      eutrophus cells and exposed to high temperature (42 degrees C) or desiccation. As
      a result, the number of culturable A. eutrophus cells which could be recovered
      from the soil samples quickly declined. However, the concentration of a marker
      gene encoding resistance to cadmium, cobalt and zinc (czc) remained unaltered.

PMID- 8261168
TI  - Glutamate uptake and synthesis by Escherichia coli cells in seawater: effects on
      culturability loss and glycinebetaine transport.
AB  - In filtered natural seawater supplemented with potassium glutamate, the ability
      of Escherichia coli MC4100 cells to grow on a complex medium was enhanced as a
      logarithmic function of the external glutamate concentration. By comparison, a
      glutamate-respiring strain of E. coli exhibited a greater decline in
      culturability in seawater, suggesting a protective influence of the accumulated
      amino acid. Potassium glutamate increased the uptake of 14C-glycinebetaine by E.
      coli MC4100 cells in seawater and enhanced the protective effects of the betaine
      against culturability loss, possibly by increasing the expression of the ProU
      transport system. This bacterium apparently was able to synthesize glutamate
      because a protective effect (i.e. a lower culturability loss) was observed in
      seawater when supplemented with precursor compounds (2-oxoglutarate and
      glutamine). The combination of 2-oxoglutarate and glutamine resulted in the
      greatest protection of cells, possibly due to the synthesis of glutamate through
      glutamine 2-oxoglutarate amino transferase activity. The possible influence of
      glutamate and its precursors on survival of E. coli cells in the natural marine
      environment is considered, since glutamate, glutamine and betaines have been
      found in marine coastal waters and sediments.

PMID- 8261169
TI  - Effect of temperature on survival of Legionella pneumophila in the aquatic
      environment.
AB  - Although Legionella spp. are often isolated from natural aquatic habitats,
      outbreaks of legionellosis are rarely traced to these sources. To determine the
      fate of Legionella pneumophila in the environment, filtered and unfiltered river
      water and seawater microcosms, incubated at 4 degrees C and 26 degrees C, were
      inoculated with [3H]thymidine-labeled L. pneumophila cells. Survival in these
      microcosms was monitored using [3H]thymidine labeling and culture on buffered
      charcoal yeast extract agar amended with alpha-ketoglutarate (BCYE alpha).
      Immunofluorescent microscopy, direct fluorescent antibody staining, and acridine
      orange direct counts were also employed. To assess effects of grazing on
      Legionella, a duplicate set of samples was filtered through 2.0-microns Nuclepore
      filters to trap large protozoa. Over the test period, in the microcosms incubated
      at 4 degrees C, the culturable counts decreased ca. 1 log on BCYE alpha agar,
      with no substantial decline in thymidine count. Autoclaved seawater and river
      water controls held at 15 degrees C also showed no change in thymidine count. At
      26 degrees C, a 3-log decline was observed in culturable counts, with ca. 1-log
      decline in thymidine counts. These results indicate that, although culturability
      declined by one to three orders of magnitude, when L. pneumophila microcosms were
      incubated at 4 degrees C and 26 degrees C, the cells remained metabolically
      active for extended periods, especially at 4 degrees C.

PMID- 8261170
TI  - A clinical overview of opportunistic infections in patients with AIDS.

PMID- 8261171
TI  - Molecular and cell biology of opportunistic infections in AIDS. Cryptosporidium
      and Isospora.

PMID- 8261172
TI  - Molecular and cell biology of opportunistic infections in AIDS. Toxoplasma.

PMID- 8261173
TI  - Molecular and cell biology of opportunistic infections in AIDS. Pneumocystis
      carinii.

PMID- 8261174
TI  - Molecular and cell biology of opportunistic infections in AIDS. Candida.

PMID- 8261175
TI  - Molecular and cell biology of opportunistic infections in AIDS. Mycoplasmas and
      AIDS.

PMID- 8261176
TI  - The application of molecular biology to the diagnosis of infectious disease.

PMID- 8261177
TI  - Molecular and cell biology of opportunistic infections in AIDS. Herpesviruses.

PMID- 8261178
TI  - Molecular and cell biology of opportunistic infections in AIDS. Future prospects.

PMID- 8261179
TI  - Molecular and cell biology of opportunistic infections in AIDS. Salmonella,
      Shigella and Campylobacter.

PMID- 8261180
TI  - Molecular and cell biology of opportunistic infections in AIDS. Mycobacteria.

PMID- 8261181
TI  - Molecular and cell biology of opportunistic infections in AIDS. Entamoeba
      histolytica.

PMID- 8261182
TI  - Staff support groups: do they support and are they even groups?
AB  - This article emphasizes the need to adopt a rigorous approach to the
      establishment of staff support groups. They are too important to be allowed to
      materialize without careful consideration of their aims, methods and composition.
      As a method of combating work-related stress they have a role to play, but it
      cannot be assumed that they will fulfil this role without serious attention being
      paid to these matters. There are good reasons for suspecting that improperly run
      support groups might have a harmful as well as a positive effect. As with all
      forms of help, the 'therapeutic' ingredients of support groups have to be
      identified and developed to ensure they fulfil their potential.

PMID- 8261183
TI  - Biography as therapy.
AB  - The feeling that life has had no meaning is an impediment to a peaceful death.
      Life review enables a person to identify events that have been of worth and so
      enhances self-esteem. This approach has been extended and formalized by
      establishing a biographer service to compile oral and written biographies of
      patients who may be expected to benefit from such a re-examination of their
      lives. The service is now also being offered to patients whose disability
      precludes most other forms of activity. The value of biography as therapy is
      considered and it is concluded that it has much to offer in the circumstances
      described.

PMID- 8261184
TI  - Communicating with people who request euthanasia.
AB  - The subject of euthanasia is widely debated in the medical literature and lay
      press in terms of morals, anecdotes and medical or legal ethics. This paper
      approaches the issue from a patient-centred perspectives, giving four case
      histories to demonstrate widely varied motives or hidden agendas for requesting
      euthanasia. It concludes with guidelines in an approach to communication which
      may empower the caregiver when confronted with a patient requesting assisted
      death or suicide.

PMID- 8261185
TI  - Eliciting the current problems of the patient with cancer--a flow diagram.
AB  - The assessment of a patient is an integral part of clinical management. It should
      be conducted in a way which maximizes the likelihood of patients disclosing all
      their main problems, whether physical, social or psychological in nature.
      Unfortunately, professional carers can be uncertain of their ability to do this.
      This flow diagram leads the carer through key points in the assessment interview.

PMID- 8261186
TI  - Pneumothorax and palliative pleural aspiration--an audit of technique.
AB  - The incidence of pneumothorax following a review of 55 single-sitting bedside
      pleural aspirations of malignant effusions over an 18-month period in the
      clinical oncology departments of the Middlesex and Mount Vernon Hospitals was
      assessed and two groups were compared. Group 1 (29 aspirations in 16 patients)
      involved a technique using an 8 ch (French) gauge trocar and cannula, a three-way
      tap and a sealed bag system, resulting in no pneumothoraces. Group 2 (26
      aspirations in 18 patients) involved a variety of other techniques with a
      pneumothorax rate of 19.2% (p = 0.0189 using Fisher's Exact Test). The small
      trocar/sealed bag system was complication-free, relatively painless, quick to
      perform, cheap, gave the option of draining to dryness and was easily learnt by
      the junior doctors who most often perform this procedure at the bedside. This
      technique is described in detail in the text. A reduction in the risk of
      pneumothorax minimizes the need for a postaspiration chest radiograph,
      facilitating aspiration in an outpatient, hospice or domiciliary setting. A
      domiciliary study is to be planned using the procedural standard described.

PMID- 8261187
TI  - Euthanasia--widening the debate.

PMID- 8261188
TI  - Prediction of life-expectancy in hospice patients: identification of novel
      prognostic factors.
AB  - The prediction of life-expectancy in terminally ill patients is important both
      for medical and social reasons but is widely recognized as being inaccurate. In
      this study we prospectively collected data items which we proposed might
      influence survival on 148 consecutive patients at first admission to one of two
      hospices. Of the 19 parameters collected, four were associated with a
      significantly shortened survival. These were low performance status (PS),
      requirement for admission at first referral to the palliative care service,
      elevated serum bilirubin, and hypotension. Factors previously identified as
      predictive of shortened survival such as hyponatraemia, weight loss, confusion
      and tumour type were not confirmed as statistically significant independent
      variables. We plan to collect these data items on future patients in order to
      test the validity of these results.

PMID- 8261189
TI  - Suitable screening tests for cognitive impairment and depression in the
      terminally ill--a prospective prevalence study.
AB  - Although confusional states and depression are common accompaniments of advanced
      cancer, few objective data are available concerning the prevalence of these
      clinical states or what methods are most suitable for their accurate detection.
      We decided that a 10-question Abbreviated Mental Test Score (AMTS) and a
      semistructured application of modified DSMIII-R (Diagnostic and Statistical
      Manual of Mental Disorder, third edition-revised) criteria for a major depressive
      illness were the most suitable screening tests for a terminally ill population.
      Thirty of 87 patients (34%) displayed significant cognitive impairment. The AMTS
      rating declined with approaching death and also correlated negatively with age.
      Of 81 patients, 21 (26%) were depressed when screened using DSMIII-R criteria for
      depression. One-third of patients with impaired AMTS scores also satisfied DSMIII
      R criteria for depression. Of cognitively impaired patients, 90% had at least two
      possible causes for their confused state. We have found that both the AMTS and
      semistructured interview using DSMIII-R criteria for depression are useful
      routine screening tests in the terminally ill.

PMID- 8261190
TI  - Spinal surgery in the treatment of metastatic back pain: three case reports.
AB  - Back pain resulting from spinal instability in metastatic bone disease can be
      difficult to alleviate by pharmacological methods and surgical intervention is
      frequently required. This paper discusses the treatment options with three
      illustrative case reports.

PMID- 8261192
TI  - The stream flows on.

PMID- 8261191
TI  - Managing the anxious patient with advancing disease--a flow diagram.
AB  - Anxiety can be one aspect of the psychological reaction to cancer and may be
      present at a clinical level. It can hinder or even prevent the diagnosis and
      management of other problems and when it develops into an anxiety state it can be
      disabling. This flow diagram describes the key clinical decisions involved in
      diagnosing and helping a patient troubled with anxiety.

PMID- 8261193
TI  - Attitudes to some aspects of death and dying, living wills and substituted health
      care decision-making in South Australia: public opinion survey for a
      parliamentary select committee.
AB  - This study aimed to provide evidence on community attitudes to certain death and
      dying issues in South Australia for a state parliamentary committee on the law
      and practice relating to death and dying. The following areas were studied: truth
      telling, pain control, level of treatment, preferred place of death, rights of
      patients to refuse treatment, opinion about living wills and substituted health
      care decision making. A representative population survey of 625 households in
      metropolitan Adelaide and three major rural centres was made in August 1991,
      using personal interviews administered at home with one adult in each household
      aged over 18 years. A total of 462 (74%) adults completed the interviews. There
      was strong support for truth-telling by doctors about incurable cancer and
      impending death, although this was not universal. Fears of potential addiction,
      habituation, tolerance and impaired cognitive function as a result of analgesia
      for cancer pain were strongly expressed, particularly amongst those who reported
      least formal education. Those with experience of a death in the last eight years
      were most likely to consider the level of treatment offered to patients with
      incurable cancer to be inadequate, but 53% considered the level to be about
      right. Nearly 60% of respondents favoured death at home, but there was a trend
      for older people to favour death in hospital. Despite the existence of the
      Natural Death Act (1982), only 20% were aware that living wills were legal in
      South Australia. There was strong support for a medical power of attorney.

PMID- 8261194
TI  - Living wills in English law.
AB  - There is considerable debate surrounding the provision of life-sustaining
      treatment to those unable themselves to give consent. This article examines the
      issues involved from a legal perspective, and discusses two proposed solutions:
      the 'advance directive' and the 'health care proxy'. It is concluded that a
      legislative framework should be set up in order to give advance directives a
      legal status.

PMID- 8261195
TI  - Short terminal admissions to a hospice.
AB  - Over a six-month period, 47 patients (9.8% of admissions) died within 48 hours of
      admission to St Christopher's Hospice and were included in this study. There was
      a high prevalence of symptoms on admission but many were amenable to treatment,
      even in the short time available. Respiratory symptoms were commonest and the
      most difficult to control. The majority of the patients required an opioid,
      although only low doses were needed. Almost all the relatives had no regrets
      about the place of death. Hospice staff felt that a number of patients
      transferred from hospital should not have been moved. The study confirmed the
      value of short terminal admissions to patients and families and suggested areas
      for further action.

PMID- 8261196
TI  - A novel morphine sulphate preparation: clinical trial of a controlled-release
      morphine suspension in cancer pain.
AB  - In order to determine the efficacy of a novel controlled-release morphine
      suspension, we performed two prospective sequential open-label studies in
      patients with pain due to cancer. The studies were identical except for the
      duration of treatment (three days and 30 days respectively). Sixty-nine patients
      with a variety of advanced cancers and associated pain participated. Fifty-three
      patients completed the trials, 38 on the three-day trial and 15 on the 30-day
      trial. In both groups the amount of morphine required to obtain pain relief was
      initially established using controlled-release morphine tablets and immediate
      release morphine for 'rescue' dosing. Patients were begun on equivalent doses of
      the study drug in place of the controlled-release tablets. No differences in pain
      score or the amount of 'rescue' morphine were noted following the switch to the
      controlled-release morphine suspension. Toxicity was as anticipated for the use
      of morphine in this situation and no adverse effects were observed during
      administration of the suspension. These data suggest that this new formulation of
      morphine is equipotent to conventional controlled-release morphine tablets and
      provides pain relief for a 12-hour dosing interval. This novel morphine
      formulation could be especially useful for paediatric patients and for those who
      have difficulty in swallowing.

PMID- 8261197
TI  - Bereavement support: evaluation of a palliative care memorial service.
AB  - A memorial service providing bereavement support in a palliative care unit is
      evaluated. Results indicate that respondents found it to be a positive
      experience, particularly in relation to its formality and content. One-fifth of
      respondents experienced distress during the service, but this was evaluated as
      appropriate, being related to personal thoughts, feelings of loss and sadness,
      and remembrance.

PMID- 8261198
TI  - Dental care of patients in a hospice.
AB  - This paper describes the dental care provided at an English hospice. Dental care
      is felt to be important because the ability to enjoy food is an important element
      in the quality of life. Over a three-year period, 67 patients were referred for
      dental advice of whom all but four were edentulous. The commonest complaint was
      of ill-fitting dentures, and the causes and possible solutions to this problem
      are reviewed.

PMID- 8261200
TI  - Faith, culture and a good death.

PMID- 8261199
TI  - Handling the withdrawn patient--a flow diagram.
AB  - The withdrawn patient challenges effective communication. Some patients are
      naturally introverted or quiet, but for others the withdrawal represents a change
      with many possible causes. This flow diagram describes the approach to a
      withdrawn patient and outlines management.

PMID- 8261201
TI  - Subcutaneous diclofenac: an effective alternative?

PMID- 8261202
TI  - Euthanasia: widening the debate. Examining outcomes is of limited value.

PMID- 8261203
TI  - Basic cardiovascular magnetic resonance imaging techniques.

PMID- 8261204
TI  - Magnetic resonance imaging evaluation of left ventricular dimensions and function
      and pericardial and myocardial disease.

PMID- 8261205
TI  - Myocardial tagging by magnetic resonance imaging.

PMID- 8261206
TI  - Congenital heart disease.

PMID- 8261207
TI  - Magnetic resonance imaging during pharmacologic stress.

PMID- 8261208
TI  - Cardiovascular magnetic resonance imaging: evaluation of myocardial perfusion.

PMID- 8261209
TI  - Cardiac nuclear magnetic resonance spectroscopy: investigations of physiology and
      diagnostic techniques.

PMID- 8261210
TI  - Reactive coagulation induced by plasmin in patients treated with recombinant
      tissue-type plasminogen activator.
AB  - BACKGROUND: We and others have demonstrated that administration of thrombolytic
      agents causes the generation of thrombosis-promoting agents. At present, we have
      studied whether formation in vivo of excessive amounts of plasmin is responsible
      for the activation of coagulation in patients treated with recombinant tissue
      type plasminogen activator. METHODS: Modified crossed immunoelectrophoresis was
      used for determination of the plasminogen-binding form of alpha 2-antiplasmin.
      Enzyme-linked immunosorbent assay methods were used for determination of
      hemostatic reaction products. RESULTS: The association between the generation of
      hemostatic reaction products and the exhaustion of the plasminogen-binding form
      of alpha 2-antiplasmin (PB alpha 2AP) was studied in 21 patients with acute
      myocardial infarction and 11 patients with unstable angina pectoris who were
      given a 3-hour, 100-mg intravenous infusion of recombinant tissue-type
      plasminogen activator (rt-PA). We observed in all patients a fall in blood
      concentrations of PB alpha 2AP (P < 0.01) after 2.25 hours of treatment and,
      simultaneously, a significant increase in fibrin degradation products (P < 0.01),
      D-dimer (P < 0.01), fibrinogen degradation products (P < 0.01), prothrombin
      fragment 1 + 2 (P < 0.01), and thrombin-antithrombin III complexes (P < 0.01).
      When we evaluated individual data, we observed high concentrations of the
      reaction products when the PB alpha 2AP concentration after 2.25 hours of
      treatment was lower than 25% of the pretreatment values. Also, we observed highly
      significant associations between the increase in the plasma concentrations of
      fibrin degradation products and thrombin-antithrombin III complexes (rs = 0.72; P
      < 0.01), the increase in plasma concentrations of fibrin degradation products and
      prothrombin fragment 1 + 2 (rs = 0.63; P < 0.01), the increase in plasma
      concentrations of D-dimer and thrombin-antithrombin III complexes (rs = 0.78; P <
      0.01), and the increase in plasma concentrations of D-dimer and prothrombin
      fragment 1 + 2 (rs = 0.79; P < 0.01). CONCLUSIONS: Generation of excessive
      amounts of plasmin is the main factor in producing the procoagulant response in
      patients who receive thrombolytic therapy with rt-PA, and intravenous heparin
      does not abolish this response. Plasmin inhibitors might be used in relation to
      thrombolytic therapy as indirect "antithrombotics."

PMID- 8261211
TI  - Characteristics of low-density lipoprotein subfractions from patients with
      coronary artery disease.
AB  - BACKGROUND: The low-density lipoprotein (LDL) of patients with coronary artery
      disease (CAD) has been reported to enhance cholesterol ester accumulation in
      aortic cells. The LDL of patients with CAD also has a higher mean density than
      the LDL of healthy subjects, indicating a different subspecies distribution.
      Because these density differences may be associated with altered metabolism and
      atherogenicity of LDL, we studied the properties and effects of isolated LDL
      subfractions on cell lipid metabolism and cholesterol accumulation. METHODS:
      Plasma pools of patients with angiographically proven CAD (A) and healthy
      controls (C) were used to isolate and fractionate LDL into five subfractions (1
      to 5, from the lowest to the highest density) by gradient ultracentrifugation.
      Each of the LDL subfractions was analyzed for particle diameter, chemical
      composition, sialic acid content, and their effect on lipid content and
      cholesterol esterification in arterial cell and macrophage cultures,
      respectively. RESULTS: The chemical compositions of the respective subfractions
      revealed no differences between patients and controls, except that the sialic
      acid content was reduced in dense LDL subfractions, especially in the samples
      from patients with CAD (fractions A3, A4, A5, and C5). LDL subfractions with
      reduced sialic acid content also enhanced the incorporation of [14C]-oleate into
      cholesterol esters in mouse peritoneal macrophage cultures (fractions A4, A5, and
      C5) and increased the cholesterol ester content in primary cultures of human
      aortic intimal cells (fractions A3, A4, A5, and C5). CONCLUSIONS: The results
      suggest that the dense LDL subfractions of patients with CAD are atherogenic by
      promoting intracellular cholesterol ester accumulation. The results also suggest
      that the atherogenicity is associated with reduced sialic acid content of the LDL
      subspecies.

PMID- 8261212
TI  - Ischemic preconditioning and long-chain acyl carnitine in the canine heart.
AB  - BACKGROUND: This study investigated the effects of ischemic preconditioning on
      myocardial carnitine-linked metabolism and high-energy phosphates in the canine
      model of ischemia and reperfusion. METHODS: Anesthetized dogs underwent 1 hour of
      coronary artery occlusion and 4.5 hours of reperfusion. The dogs were randomly
      assigned to a control group (no intervention for 30 minutes), a preconditioned
      group (four repeated episodes of 3 minutes of mechanical coronary occlusion, each
      followed by 5 minutes of reperfusion), and a coronary cyclic flow variation (CFV)
      group (coronary artery stenosis and endothelial injury, resulting in an average
      of four episodes of platelet thrombosis and dislodgment). After completion of the
      protocol, ATP, creatine phosphate, and long-chain acyl carnitine concentrations
      were studied in both nonischemic and previously ischemic myocardium. RESULTS: In
      Part I of this study (Ovize et al., Circulation 1992, 85:779-789), it was
      reported that both mechanical occlusion and CFV before sustained occlusion
      resulted in a decrease in infarct size. In the present paper, we report changes
      in high-energy phosphates and long-chain acyl carnitine in these groups. Control,
      preconditioned, and CFV groups showed similar depletion in ATP content and
      "overshoot" in creatine phosphate stores. Control dogs exhibited a significant
      accumulation of long-chain acyl carnitine in the previously ischemic tissue (219
      +/- 61 vs 131 +/- 38 nmoles/g wet weight in the nonischemic tissue; P < 0.05). No
      significant increase in long-chain acyl carnitine occurred in the mechanically
      preconditioned and CFV groups. CONCLUSIONS: These results indicate that brief
      episodes of transient ischemia before sustained coronary occlusion prevent long
      chain acyl carnitine accumulation in the ischemic and reperfused canine
      myocardium.

PMID- 8261213
TI  - Should health care for the elderly be rationed?

PMID- 8261214
TI  - Bibliography of the current world literature.

PMID- 8261215
TI  - Perioperative hypertension: an overview.

PMID- 8261216
TI  - Intraoperative transesophageal echocardiography: state of the art and future
      directions.

PMID- 8261217
TI  - Anesthetic-induced myocardial ischemia: the isoflurane-coronary steal
      controversy.

PMID- 8261218
TI  - Adverse reactions to protamine.

PMID- 8261219
TI  - Electrocardiographic signs of coronary heart disease in a "low risk" population
      in rural Crete.
AB  - BACKGROUND: Ischemic heart disease (IHD) has been shown to be very uncommon in
      the population of Crete. Therefore, we established a research project in a rural
      part of Crete to survey the cardiovascular risk profile and follow the incidence
      of cardiovascular disease over time. This study investigated the prevalence of
      ECG abnormalities in the population of five villages and compared the prevalence
      of hypertension, obesity, diabetes, and hypercholesterolemia in those with and
      without ECG signs of IHD. METHODS: A cross-sectional study was conducted in a
      group from 15 to 79 years of age (n = 1218); overall attendance was 926 (76%).
      Studies included case history, clinical status, laboratory variables, and 12-lead
      ECG. Technically acceptable ECGs were read and coded blindly for 895 subjects
      (97%). RESULTS: Minnesota codes suggesting "Probable IHD" were recorded in 3.3%
      of the women and 3.5% of the men from 45 to 79 years of age. Hypertension was
      more common in subjects with than in those without "Probable IHD." This also
      tended to be the case for diabetes. Cholesterol and body mass index were
      relatively high in both groups. CONCLUSIONS: The present prevalence of "Probable
      IHD" in Cretans appears to be very similar to that observed in other population
      surveys. Also, the contemporary cardiovascular risk factor profile in the
      population was quite unfavorable, with a relatively high prevalence of smoking,
      dyslipidemia, hypertension, and diabetes. The prevalence of "Probable IHD" was
      lowest in the village where the health center was situated (1% vs 4.5%), and this
      difference was also reflected in differences among the villages of some important
      risk factors for IHD as well as in the way patients with hypertension and other
      diseases were cared for. Thus, it seems IHD is becoming more prevalent in the
      "low risk" population of Crete. This may very well be a result of a more
      unfavorable lifestyle and a higher rate of risk factors than before.

PMID- 8261220
TI  - Platelet-derived growth factor is released into the coronary circulation after
      coronary spasm.
AB  - BACKGROUND: Platelet-derived growth factor (PDGF) is a potent mitogen for
      vascular smooth muscle cells and is implicated in the vascular response to injury
      and the pathogenesis of atherosclerosis. It is also a potent vasoconstrictor.
      METHODS: To examine whether acute myocardial ischemia increases the level of PDGF
      in the coronary circulation, we measured plasma levels of PDGF in the coronary
      sinus and the aortic root simultaneously in 14 patients with coronary spastic
      angina. These measurements were performed before and after the left coronary
      artery spasm induced by intracoronary injection of acetylcholine, and
      measurements were also taken in 15 patients with stable exertional angina before
      and after acute myocardial ischemia induced by rapid atrial pacing. Eleven
      patients with chest pain but normal coronary arteries and no coronary spasm
      served as controls. RESULTS: Plasma PDGF levels increased significantly (P <
      0.01) from 274 +/- 28 pg/mL to 364 +/- 27 pg/mL only in coronary sinus after
      anginal attacks in the patients with coronary spastic angina. However, plasma
      PDGF levels in coronary sinus remained unchanged after these attacks in the
      patients with stable exertional angina (from 230 +/- 27 pg/ml to 247 +/- 28
      pg/mL) and after intracoronary injection of acetylcholine in the control
      subjects. Plasma PDGF levels in aortic root remained unchanged in all three
      patient groups. CONCLUSIONS: PDGF is released into the coronary circulation after
      coronary artery spasm, and this may exacerbate coronary artery spasm.

PMID- 8261221
TI  - Cicletanine attenuates overdrive pacing-induced global myocardial ischemia in
      rabbits: possible role of cardiac cyclic nucleotides.
AB  - BACKGROUND: This study examined whether cicletanine, an antihypertensive drug
      with cGMP phosphodiesterase inhibitory effect, could alleviate ventricular
      overdrive pacing-induced myocardial ischemia in chronically instrumented rabbits.
      METHODS: An electrode-catheter implanted into the right ventricle was used for
      pacing (500 bpm over 5 min) and for measuring intracavital ST-segment elevation
      and ventricular effective refractory period (VERP). PQ and QT intervals were
      measured in the chest-lead ECG, and dP/dtmax as well as left ventricular end
      diastolic pressure (LVEDP) were recorded through a left intraventricular
      catheter. In separate groups, mean arterial blood pressure (MABP) was monitored
      from the right carotid artery. Experiments were performed on conscious rabbits
      after a week of convalescence. In anesthetized, open-chest rabbits, samples were
      taken from the left ventricle before and after drug treatment and/or overdrive
      pacing for determination of cGMP and cAMP contents by radioimmunoassay. RESULTS:
      Intravenous cicletanine, 30 mg/kg body weight, did not change resting MABP,
      dP/dtmax, and LVEDP, but it did reduce heart rate and prolonged PQ and QT
      intervals and VERP. Overdrive pacing produced intracavital ST-segment elevation,
      increased LVEDP, and decreased dP/dtmax and MABP. Cicletanine administered 15
      minutes before pacing significantly attenuated ST-segment elevation, increased
      LVEDP, and decreased dP/dtmax and MABP. In anesthetized animals, cicletanine
      itself slightly increased cardiac cGMP and cAMP contents. Overdrive pacing
      moderately increased cGMP and profoundly elevated cAMP, and in overpaced rabbits,
      cicletanine further increased cGMO and markedly attenuated cAMP content increased
      by overdrive pacing. CONCLUSIONS: These results suggest that in correlation with
      alterations of cardiac cycle nucleotide contents, cicletanine protects the heart
      against pacing-induced myocardial ischemia.

PMID- 8261222
TI  - Local calcification as a determinant of the outcome of excimer laser coronary
      angioplasty: an in vitro study.
AB  - BACKGROUND: Calcification influences the outcome of various angioplasty
      techniques in the treatment of coronary artery disease. During angioscopic in
      vitro studies, we observed that dissections and perforations not caused by vessel
      bending frequently occurred at the boundary areas of plaque and adjacent vessel
      wall. This study investigated whether this is related to the distribution of
      calcific deposits. METHODS: Postmortem excimer laser coronary angioplasty (308-nm
      XeCl) was performed in 51 stenotic coronary arteries. Twenty-three segments were
      further examined; these consisted of 11 perforations, six dissections, three
      segments with no ablative effect after the application of 20,000 laser impulses,
      and three successfully passed stenoses without complications. X-ray diffraction
      analysis and scanning electron microscopy were performed to detect calcium
      deposits and their spatial relationship to perforations and dissections. RESULTS:
      X-ray diffractions analysis detected calcifications in 21 of 23 specimens.
      Postmortem angiography revealed calcifications only on 11 of 23 segments. Three
      of 11 perforations were located at the plaque border, as were three of six
      dissections. In all six complications at the plaque border, x-ray diffraction
      analysis revealed that the plaque border was identical with a border of calcium
      deposits. Eight of 11 perforations and three of six dissections could be
      explained by axis divergence between the laser catheter and the vessel
      orientation. CONCLUSIONS: Contributing factors for perforations and dissections
      during excimer laser coronary angioplasty are axis divergence and the
      distribution of plaque calcification. More sensitive methods are needed to detect
      local vessel wall calcium in vivo.

PMID- 8261223
TI  - Enalapril in the prevention of restenosis following intracoronary intervention in
      a swine model.
AB  - BACKGROUND: Restenosis following percutaneous transluminal coronary angioplasty
      continues to be a major limitation of the procedure. To test whether an
      angiotensin-converting enzyme inhibitor may reduce restenosis, this study
      utilized an atherosclerotic, stented, Hanford miniature swine model of
      restenosis. METHODS: Each animal first was started on an atherogenic diet and had
      balloon abrasion of the left anterior descending and right coronary arteries.
      Four months later, balloon-mounted coil stents were placed into the abraded
      coronary arteries of each animal. Twenty-four animals then were randomly assigned
      to one of two groups: enalapril, and control. The enalapril group received 50 mg
      orally twice daily starting 1 week before intracoronary stenting. RESULTS: Follow
      up 2 months later revealed angiographic stenosis in the control group of 30% +/-
      13%/25% +/- 10% (left anterior descending/right coronary artery) versus 37% +/-
      9%/20% +/- 11% in the enalapril group (P = not significant). The change in
      minimal lumen diameter from immediately after stenting to follow-up was not
      significantly different between control and enalapril groups. Area stenosis and
      maximal intimal thickness obtained by morphometric analysis were also compared,
      and the mean percentage area stenosis for the control group was 39 +/- 12%/31% +/
      16% and for enalapril 36% +/- 14%/35% +/- 19%. The maximal intimal thickness in
      the control group was 573 microns +/- 204 microns/605 microns +/- 266 microns and
      in the enalapril group 530 microns +/- 220 microns/424 microns +/- 237 microns.
      There was no statistical difference. CONCLUSIONS: Enalapril fails to reduce
      restenosis in this animal model.

PMID- 8261225
TI  - Bibliography of the current world literature.

PMID- 8261224
TI  - Local drug delivery catheters: functional comparison of porous and microporous
      designs.
AB  - BACKGROUND: The porous (Wolinski) balloon was designed to allow local delivery of
      compounds targeted to inhibit postintervention restenosis; however, successful
      use of the device has been hampered by arterial trauma caused by the balloon
      itself. This study utilized several experimental systems to assess the functional
      characteristics of the porous balloon catheter. This information was utilized to
      design and test a new microporous infusion catheter for local intra-arterial drug
      delivery. METHODS: Flow characteristics in fluid and semisolid media as well as
      arterial trauma by light and electron microscopy were documented for the porous
      and microporous balloons. In addition, the efficacy of methylene blue delivery in
      situ and in vitro was documented and quantified for the microporous design.
      RESULTS: The porous balloon exhibits flow characteristics consistent with orifice
      related streaming that produces arterial trauma. By maximizing external balloon
      pore density and minimizing pore size, the microporous design minimizes streaming
      in test systems. This is manifested by minimal arterial trauma when applied to
      intact arteries. The microporous catheter is effective for dye delivery both in
      situ and in vivo. CONCLUSIONS: The microporous catheter design offers improved
      functional characteristics when compared with the porous balloon for local intra
      arterial drug delivery.

PMID- 8261226
TI  - Myocardial viability: evidence provided by the analysis of left ventricular
      systolic function.

PMID- 8261227
TI  - Flow and metabolic determinants of myocardial viability assessed by positron
      emission tomography.

PMID- 8261228
TI  - Flow and cellular function: clinical assessment of myocardial viability by single
      photon agents.

PMID- 8261229
TI  - Disparity in coronary perfusion and regional wall motion: effect on clinical
      assessment of viability.

PMID- 8261230
TI  - Assessment of myocardial viability by use of multiple clinical parameters and
      effect on prognosis.

PMID- 8261231
TI  - Patterns of coronary artery stenosis vasomotion: observed versus "predicted"
      stenosis reactivity in patients with chronic stable angina.
AB  - BACKGROUND: Patterns of constriction and dilatation of angiographically normal
      coronary artery segments and coronary stenoses, in response to vasoactive
      stimuli, remain speculative. METHODS: We compared the vasomotor response of
      angiographically normal and stenotic coronary segments and assessed the effects
      of stenosis location and morphology on coronary stenosis vasomotion in 52
      patients with chronic stable angina (40 men and 12 women) who underwent
      intracoronary ergonovine or isosorbide dinitrate administration or both. Changes
      in coronary diameter in response to nitrate and ergonovine were assessed by
      computed arteriography. The "predicted" change in stenosis diameter was
      calculated according to the "geometric theory" (based on the vasomotor response
      of angiographically normal segments adjacent to the lesion and on stenosis
      severity). Coronary diameter was assessed at baseline and after nitrate
      administration in 58 stenoses (34 concentric and 24 eccentric), of which 40 were
      located proximally and 18 distally, and also after ergonovine administration (23
      stenoses: 14 proximal and 9 distal, 14 concentric and 9 eccentric). RESULTS:
      Significant (> or = 10% lumen diameter change) vasoconstriction was observed
      after ergonovine administration in 14 of the 23 stenoses (61%), and significant
      vasodilation was noted after nitrate administration in 29 of 58 stenoses (50%). A
      larger proportion of distal (89%) and eccentric (89%) compared with proximal
      (43%) and concentric (43%) stenoses showed a greater than 10% vasoconstriction
      after ergonovine administration (P < 0.05). Vasodilatation after nitrate
      administration was also observed in a larger proportion of distal (78%) and
      eccentric (67%) than in proximal (38%) and concentric (38%) stenoses (P < 0.05).
      On average, the "observed" changes in coronary diameter in response to nitrate
      and ergonovine administration were of significantly less magnitude than those
      "predicted" by the geometric theory in both proximal and distal stenoses and in
      concentric and eccentric stenoses. In only 17% of stenoses were observed and
      predicted vasoconstriction similar. CONCLUSIONS: Our results suggest that in
      patients with chronic stable angina, calculations based on the "geometric theory"
      cannot predict the actual vasomotor response of a stenosis. Factors other than
      severity, such as baseline coronary tone, stenosis location, and stenosis
      morphology, appear to modulate stenosis vasomotion in vivo.

PMID- 8261232
TI  - Cardiac troponin T release in acute myocardial infarction is associated with
      scintigraphic estimates of myocardial scar.
AB  - BACKGROUND: This study compared clinical-chemical estimates of infarct size with
      scintigraphic estimates of myocardial scar in patients with first-time acute
      myocardial infarction (AMI). METHODS: Levels of the cardiac isoform of the
      contractile protein troponin T (TnT), of creatine kinase (CK), and of the
      isoenzyme MB of CK (CK MB) were tested in serially drawn blood samples from 21
      patients (two females and 19 males; median age, 55 years). Of these 21 patients,
      five had anterior- and 16 had inferior-wall AMI; all patients received
      intravenous thrombolytic therapy. Single-photon emission computed tomography
      (SPECT) with technetium-99m-isonitrile (Tc-sestamibi) was performed at rest after
      the onset of AMI (median time, 5 weeks). Scintigraphic defects were calculated
      using "bull's-eye" polar coordinate maps. All patients had an uncomplicated
      course between discharge and myocardial scintigraphy. RESULTS: Scintigraphic
      defect sizes ranged from 3.2% to 47.8% of the left ventricle (median, 27.3%).
      Cardiac TnT and CK MB release correlated closely with each other and with
      scintigraphic estimates of myocardial scar. Significant correlates were found
      between cardiac TnT and CK MB peak values (r = 0.87, P = 0.0001), CK MB peaks and
      Tc-sestamibi defect sizes (r = 0.73, P = 0.0014), and TnT peaks and scintigraphic
      defect sizes (r = 0.73, P = 0.0011). CONCLUSIONS: Because animal studies have
      already shown a very close correlation between histologic infarct size and SPECT
      Tc-sestamibi defect size, our results indicate that cardiac TnT is a useful
      marker to assess infarct size noninvasively in man.

PMID- 8261233
TI  - Hemodynamic effects of atrial interaction.
AB  - BACKGROUND: Ventricular pressure and volume overload may induce hemodynamically
      important ventricular interactions mediated by the thick interventricular septum.
      The purpose of this study was to determine whether analogous hemodynamically
      manifest atrial interactions occur across the thinner interatrial septum.
      METHODS: Right atrial (RA) and left atrial (LA) pressures were measured with
      micromanometer-tipped catheters before and after atrial pressure and volume
      overload elicited by sequential right ventricular (RV), RA, and septal ischemia
      induced in nine open-chest dogs. RESULTS: Following RV ischemia, RA pressure
      increased and RA contraction and relaxation were enhanced, as indicated by an
      augmented A wave and X descent. Despite decreased LV diastolic size, LA pressure
      increased, with similar increases in its A wave and X descent. RA ischemia
      depressed RA contraction and relaxation, resulting in diminished A wave and X
      descent. Parallel changes occurred in the LA waveform. Following septal ischemia,
      LA contraction and relaxation were enhanced, as reflected in an augmented A wave
      and X descent. Despite persistent RA ischemia, the RA A wave and X descent
      increased. CONCLUSIONS: These findings demonstrate interatrial transmission of
      pressure and waveform changes that may influence hemodynamic evaluation and
      cardiac function.

PMID- 8261234
TI  - "Syndrome X" and coronary artery disease.
AB  - BACKGROUND: "Syndrome X" is a heterogeneous disorder that probably encompasses
      several disease states. The long-term prognosis in syndrome X is good, although a
      significant number of patients continue to experience chest pain and remain
      functionally limited. Several studies have reported that the development of
      coronary artery disease in patients with syndrome X is rare. Our experience,
      however, has shown that patients diagnosed as having syndrome X may develop
      atherosclerotic coronary artery disease over a relatively short period of time.
      METHODS: Three patients with syndrome X were studied with repeat coronary
      angiography. RESULTS AND CONCLUSIONS: We describe the development of coronary
      artery disease in three syndrome X patients over a relatively short time after
      their normal coronary angiogram. Accordingly, the physician should remain alert
      to this possibility.

PMID- 8261235
TI  - An additional marker for familial hypertrophic cardiomyopathy?
AB  - BACKGROUND: Family screening for hypertrophic cardiomyopathy using conventional
      techniques yields some equivocal cases. Although mutations in the beta-cardiac
      myosin heavy-chain gene (MYH7) have been demonstrated in some patients,
      additional diagnostic methods are desirable to clarify the equivocal cases until
      the full genetic spectrum is characterized. Because coronary flow reserve is
      reduced in patients with typical hypertrophic cardiomyopathy independent of the
      severity of left ventricular hypertrophy, this measurement may help to identify
      patients with equivocal features of the disease. METHODS: Coronary flow reserve
      was measured in two subjects: one with a MYH7 mutation but without typical
      diagnostic features of hypertrophic cardiomyopathy, and one with borderline left
      ventricular hypertrophy but no mutation in the MYH7 gene. Both subjects underwent
      screening for hypertrophic cardiomyopathy because of a family history of the
      disease. Positron-emission tomography was performed to measure myocardial blood
      flow (MBF) with oxygen-15 labeled water. MBF was measured at baseline and during
      coronary vasodilatation obtained by intravenous dipyridamole (0.56 mg/kg body
      weight infused over 4 minutes). Coronary flow reserve was expressed as the ratio
      MBF-dipyridamole/MBF-baseline. RESULTS: Coronary flow reserve was 1.69 and 1.12
      in the two subjects. Both of these values are 2 SD below that (3.87 +/- 1.08)
      measured in 17 normal subjects using the same method. CONCLUSIONS: Noninvasive
      quantification of coronary flow reserve by positron-emission tomography may have
      a role in identifying patients with equivocal hypertrophic cardiomyopathy and
      should be further explored.

PMID- 8261236
TI  - Septal glucose metabolism in patients with coronary artery disease and left
      bundle-branch block.
AB  - BACKGROUND: Positron-emission tomography (PET) using 18F-deoxyglucose (FDG) is
      used for assessment of myocardial viability in regions with impaired resting
      perfusion and contractility. This report describes FDG-PET septal findings in six
      patients with complete left bundle-branch block (LBBB) and chronic coronary
      artery disease (CAD) compared to a reference population without LBBB. METHODS:
      All patients had documented left anterior descending artery stenosis and septal
      wall-motion abnormality. Attenuation-corrected PET scans were acquired after the
      administration of oral glucose load, and myocardial perfusion at rest was
      assessed using 99mTc-methoxyisobutylisonitrile (MIBI) single-photon emission
      computed tomography (SPECT). Myocardial FDG and MIBI uptake in 25 regions of
      interest were expressed as percentage uptake of the individual reference region,
      and average uptake values as well as the FDG/MIBI ratio were calculated for the
      entire septum and lateral wall. RESULTS: Relative to septal MIBI uptake, septal
      FDG uptake was decreased in patients with LBBB and increased in patients with
      LBBB. The septal FDG/MIBI ratio was significantly lower in patients with LBBB
      than in those without LBBB (0.62 +/- 0.12 vs 1.24 +/- 0.24, respectively; P <
      0.001) and did not exceed 0.8 in patients with LBBB. In patients without LBBB,
      the ratio constantly exceeded 0.8. CONCLUSIONS: In patients with LBBB and CAD,
      septal reduction of FDG uptake may significantly exceed the reduction of septal
      perfusion as assessed by MIBI-SPECT. Decreased septal FDG uptake may be
      attributed in part to the conduction abnormality, resulting in limited value for
      this tool as an assessment of septal viability in this patient group.

PMID- 8261237
TI  - Bibliography of the current world literature.

PMID- 8261238
TI  - New conduits for coronary artery bypass.

PMID- 8261239
TI  - Myocardial protection for coronary artery disease.

PMID- 8261240
TI  - PTCA failure.

PMID- 8261241
TI  - Coronary reoperations.

PMID- 8261242
TI  - Ischemic cardiomyopathy: the role of coronary artery bypass.

PMID- 8261243
TI  - Constitutive biosynthesis of plasminogen activator inhibitor type-1 (PAI-1) by
      cultured human aortic endothelial cells independent of insulin.
AB  - BACKGROUND: Both tissue-type plasminogen activator (t-PA) and plasminogen
      activator inhibitor type-1 (PAI-1) are synthesized by vascular endothelium,
      whereas hepatocytes synthesize PAI-1 but not t-PA. Non-insulin-dependent diabetes
      mellitus (NIDDM) is associated with decreased fibrinolytic activity in blood
      secondary to increased PAI-1 activity, and the increase in PAI-1 activity is
      correlated with the magnitude of elevation of plasma immunoreactive insulin. To
      determine whether the increased PAI-1, known to be associated with accelerated
      coronary artery disease in non-diabetic subjects, is a consequence of direct
      effects of insulin on endothelial cells, we performed the present study with
      primary cultures of human aortic endothelial cells. METHODS: Endothelial cells
      isolated from human aortas from donor hearts for transplantation were grown to
      confluence and exposed to selected concentrations of agonists. Accumulation of t
      PA and PAI-1 in conditioned media was quantified, as was PAI-1 activity. RESULTS:
      Insulin at pharmacologic concentrations did not alter either PAI-1 or t-PA
      production by the human aortic endothelial cells, although insulin stimulated PAI
      1 synthesis in human hepatoma (Hep G2) cells as expected. Transforming growth
      factor-beta (TGF-beta) stimulated endothelial cell PAI-1 production markedly,
      indicating that the cells could respond positively to stimulation in vitro. PAI-1
      activity in the conditioned media was zero under all conditions, which was
      indicative of the rapid inactivation and degradation of PAI-1 known to occur in
      media devoid of vitronectin. CONCLUSIONS: The decreased fibrinolytic activity in
      blood seen in patients with NIDDM appears to reflect direct effects of insulin or
      its precursor on hepatocytes rather than on endothelial cells.

PMID- 8261244
TI  - Dipyridamole thallium imaging: use in preoperative cardiac risk assessment in
      vascular surgical patients.
AB  - BACKGROUND: The objective of this study was to determine whether routine
      performance of dipyridamole thallium imaging adds to the power of a careful
      clinical evaluation in the risk stratification of patients undergoing major
      vascular surgery. METHODS: In this retrospective study, 115 cases evaluated by
      dipyridamole thallium imaging before major vascular surgery were reviewed.
      Patients were assigned to a high-risk cohort if they had a history of congestive
      heart failure or evidence of previous myocardial infarction. RESULTS: Six (8%)
      patients from the high-risk cohort developed major cardiovascular complications.
      Reversible perfusion defects, present in 67% of the high-risk patients, did not
      predict complications. None of the patients in the low-risk cohort developed
      complications despite the presence of reversible perfusion defects in 33%.
      Patients in the high-risk cohort who underwent cardiac catheterization and
      selective coronary bypass grafting were uniformly free of perioperative
      complications. The extent and severity of fixed or reversible thallium perfusion
      did not predict the occurrence of cardiovascular complications. However, three
      patients were denied surgery following an unacceptable cardiovascular risk
      assessment based on clinical findings and multiple reversible thallium perfusion
      defects. CONCLUSION: In low-risk patients, screening with dipyridamole thallium
      can identify patients with redistribution defects whose risk of perioperative
      ischemic events can be reduced by intensifying perioperative anti-ischemic
      management. If the patient is in the high-clinical-risk subgroup, screening with
      dipyridamole thallium does not identify a cohort with negligible perioperative
      risk; thus, further evaluation of these patients by cardiac catheterization
      should be considered.

PMID- 8261245
TI  - Relative prognostic value of clinical, exercise, and angiographic data after a
      first myocardial infarction.
AB  - BACKGROUND: Studies examining the relative value of clinical, exercise test, and
      angiographic data in the prediction of further clinical events after a first
      acute myocardial infarction (AMI) have produced conflicting results. METHODS: We
      examined the relative value of clinical, exercise test, and angiographic data as
      predictors of death, recurrent infarction, and the subsequent development of
      angina or dyspnea in 303 consecutive patients who underwent exercise testing and
      coronary angiography within 2 months of an uncomplicated first acute myocardial
      infarction (AMI), and who were followed for 48 (+/- 22) months. RESULTS: A
      combination of two clinical and two exercise variables correctly identified 79%
      of subsequent deaths. No variables had a predictive value for re-infarction. A
      combination of two exercise variables correctly identified 75% of patients who
      developed angina during follow up. A combination of two clinical variables and
      one exercise variable correctly identified 76% of patients who developed dyspnea
      during follow up. CONCLUSIONS: Exercise testing provided useful prognostic
      information independent of clinical data. Combining clinical and exercise data
      identified a group of patients at low risk of future events. In this low-risk
      group of patients, the addition of angiographic data did not provide additional
      prognostic information.

PMID- 8261247
TI  - Bibliography of the current world literature.

PMID- 8261246
TI  - Impact of radiofrequency ablation procedures on the management of arrhythmias.

PMID- 8261248
TI  - The estimation of the basic reproduction number for infectious diseases.
AB  - The basic reproduction number R0 is the number of secondary cases which one case
      would produce in a completely susceptible population. It depends on the duration
      of the infectious period, the probability of infecting a susceptible individual
      during one contact, and the number of new susceptible individuals contacted per
      unit of time. Therefore R0 may vary considerably for different infectious
      diseases but also for the same disease in different populations. The key
      threshold result of epidemic theory associates the outbreaks of epidemics and the
      persistence of endemic levels with basic reproduction numbers greater than one.
      Because the magnitude of R0 allows one to determine the amount of effort which is
      necessary either to prevent an epidemic or to eliminate an infection from a
      population, it is crucial to estimate R0 for a given disease in a particular
      population. The present paper gives a survey about the various estimation methods
      available.

PMID- 8261249
TI  - Statistical models for estimating prevalence and incidence of parasitic diseases.
AB  - The estimation of prevalence and incidence of parasitic infections is considered.
      As the detectability of such infections is not 100% and may furthermore depend on
      their intensity, statistical methods are often required to arrive at meaningful
      results. It appears to be essential to distinguish between parasites that
      multiply within the (human) host and those that do not. An overview of some
      models discussed in the literature is presented. These models can indeed be used
      in assessing detectability of infection, and they indicate that observations may
      lead to considerable misinterpretation of 'true' prevalences and incidences.

PMID- 8261250
TI  - Statistical modelling of measles and influenza outbreaks.
AB  - This paper reviews the application of statistical models to outbreaks of two
      common respiratory viral diseases, measles and influenza. For each disease, we
      look first at its epidemiological characteristics and assess the extent to which
      these either aid or hinder modelling. We then turn to the models that have been
      developed to simulate geographical spread. For measles, a distinction is drawn
      between process-based and time series models; for influenza, it is the scale of
      the communities (from small groups to global populations) which primarily
      determines modelling style. Applications are provided from work by the authors,
      largely using Icelandic data. Finally we consider the forecasting potential of
      the models described.

PMID- 8261251
TI  - AIDS: the statistical basis for public health.
AB  - The backcalculation method has been extensively used in AIDS modelling and
      forecasting. Knowledge of reported AIDS cases, information on the time between
      HIV infection and onset of AIDS, and assumptions on the rate at which infections
      occurs, can be used to reconstruct the past history of the HIV epidemic, as well
      as to provide short term predictions of AIDS incidence. Uncertainty in the three
      components of the backcalculation method and the increasingly available
      information on HIV prevalence must be taken into account in order to provide
      realistic projections. In this paper we discuss ways of acknowledging uncertainty
      and suggest a Bayesian formulation of the backcalculation idea as a means of
      combining into a single model both random and systematic variation as well as
      prior information.

PMID- 8261252
TI  - Martingale methods for the analysis of epidemic data.
AB  - After explaining why martingale methods play an important role in statistical
      inference for parameters of epidemic models, we give a tutorial introduction to
      these methods in the more familiar context of data on independent and identically
      distributed survival times. In this simpler setting we introduce requisite
      results from martingale theory and demonstrate that martingale methods simply
      lead to well known estimates and their standard errors. We then turn to the
      context of epidemics, and illustrate how martingale methods can be used to derive
      a method of inference for the infection potential in a simple model with removal
      of infectives. The resulting method involves only simple computations and we
      demonstrate that the method applies under much more general assumptions. There
      follows a critical review of several applications of martingale methods for the
      analysis of infectious disease data. It emerges that the approach provides simple
      methods of inference in some situations where standard methods of inference are
      not available, or are too cumbersome. The range of applications seems limited,
      but new applications continue to be found. Little has been done to confirm high
      efficiency of martingale methods in epidemic applications.

PMID- 8261253
TI  - Meta-analysis.

PMID- 8261254
TI  - The statistical basis of meta-analysis.
AB  - Two models for study-to-study variation in a meta-analysis are presented,
      critiqued and illustrated. One, the fixed effects model, takes the studies being
      analysed as the universe of interest; the other, the random effects model, takes
      these studies as representing a sample from a larger population of possible
      studies. With emphasis on clinical trials, this paper illustrates in some detail
      the application of both models to three summary measures of the effect of an
      experimental intervention versus a control: the standardized difference for
      comparing two means, and the relative risk and odds ratio for comparing two
      proportions.

PMID- 8261255
TI  - The logic and role of meta-analysis in clinical research.
AB  - The term meta-analysis refers to the quantitative combination of data from
      independent trials. Where the result of such combination is a descriptive summary
      of the weight of the available evidence, the exercise is of undoubted value.
      Attempts to apply inferential methods, however, are subject to considerable
      methodological and logical difficulties. The selection and quality of the trials
      included, population bias, and the specification of the population to which
      inference may properly be made are problems to which no satisfactory solutions
      have been proposed. Insightful quantitative description ought not to differ
      materially from inferential conclusions; where discrepancies exist the
      inferential techniques should be regarded with extreme caution.

PMID- 8261256
TI  - Meta-analytic stimulus for changes in clinical trials.
AB  - The advent of meta-analysis, especially when performed cumulatively, raises many
      questions about how best to approach the conduct of clinical trials in the
      evaluation of new treatments. We need to be assured that bias is minimized by
      proper experimental procedures and that clinical data, on the whole and in
      subgroups, are presented so that they can be effectively combined in meta
      analysis. We need to re-examine the idea that we should not start a randomized
      control trial unless sufficient patients are available to avoid reasonable type I
      and II errors. Meta-analyses will come to the rescue, provided trials continue to
      be published at the present rate. We need to perform meta-analyses before
      undertaking each additional trial, and we need to base estimates of trial size on
      past data as well as the expected control rates and the differences we do not
      want to miss. In clinical trials of new interventions attempting to disprove the
      null hypothesis may be inappropriate because past data so often suggest or even
      establish that it is not true. Furthermore we need to recognize that trends (p >
      0.05) can be both clinically and statistically important, and we must abandon the
      notion that if p is not < 0.05, the treatment is ineffective. In performing meta
      analyses we need to worry about minimizing bias and error and consider the
      differences between the random and fixed effects models and between reporting
      results as an odds ratio versus difference in risk, with the control rates given.
      Experiences with cumulative meta-analysis have required that we think about all
      of these problems.

PMID- 8261257
TI  - Controversies in meta-analysis: the case of the trials of serum cholesterol
      reduction.
AB  - There has recently been disagreement in the literature on the results and
      interpretation of meta-analyses of the trials of serum cholesterol reduction,
      both in terms of the quantification of the effect on ischaemic heart disease and
      as regards the evidence of any adverse effect on other causes of death. This
      paper describes statistical aspects of a recent meta-analysis of these trials,
      and draws some more general conclusions about the methods used in meta-analysis.
      Tests of an overall null hypothesis are shown to have a basis clearly distinct
      from the more extensive assumptions needed to provide an overall estimate of
      effect. The fixed effect approach to estimation relies on the implausible
      assumption of homogeneity of treatment effects across the trials, and is
      therefore likely to yield confidence intervals which are too narrow and
      conclusions which are too dogmatic. However the conventional random effects
      method relies on its own set of unrealistic assumptions, and cannot be regarded
      as a robust solution to the problem of statistical heterogeneity. The random
      effects method is more usefully regarded as a type of sensitivity analysis in
      which the weights allocated to each study in estimating the overall effect are
      modified. However, rather than using a statistical model for the 'unexplained'
      heterogeneity, greater insight and scientific understanding of the results of a
      set of trials may be obtained by a careful exploration of potential sources of
      heterogeneity. In the context of the cholesterol trials, the heterogeneity
      according to the extent and duration of cholesterol reduction are of prime
      concern and are investigated using logistic regression. It is concluded that the
      long-term benefits of serum cholesterol reduction on the risk of heart disease
      have been seriously underestimated in some previous meta-analyses, while the
      evidence for adverse effects on other causes of death have been misleadingly
      exaggerated.

PMID- 8261258
TI  - Variance components for statistical genetics: applications in medical research to
      characteristics related to human diseases and health.
AB  - RA Fisher introduced variance components in 1918. He synthesized Mendelian
      inheritance with Darwin's theory of evolution by showing that the genetic
      variance of a continuous trait could be decomposed into additive and non-additive
      components. The model can be extended to include environmental factors,
      interactions, covariation, and non-random mating. Identifiability depends
      critically on design. Methods of analysis include modelling the mean squares from
      a fixed effects analysis of variance, and covariance structure modelling, which
      can be extended to multivariate traits and has been used to study ordinal traits
      by reference to postulated, unmeasured, latent 'liabilities'. These methods
      operate on dependent observations within independent groups of the same size and
      structure, and therefore require balanced designs ('regular' pedigrees). A
      multivariate normal model handles data in its generic form, utilizes data
      efficiently from all members of pedigrees of unequal size or varying structure,
      accommodates individuals missing at random, and allows flexible modelling with
      tests of distributional assumptions and fit. Most analytical methods use least
      squares or maximum likelihood under normal theory. Robust methods, scale
      transformation, ascertainment, path diagrams and correlational path models
      (popular in behavioural genetics through addressing nonrandom mating and social
      interactions), 'heritability', and the contribution and limitations of
      statistical modelling to the 'nature-nurture' debate, are discussed.

PMID- 8261259
TI  - Analysis of DNA sequences.
AB  - Recent developments in the statistical analysis of DNA sequences are reviewed.
      The pace with which sequence data are being generated and analysed has increased
      with the growth of the human genome project. Two areas of activity are
      emphasized: attention to error rates in recorded sequences, and heterogeneity in
      structure of sequences. There is now empirical evidence suggesting error rates in
      the range 0.1%-1%, and such rates will affect evolutionary studies since these
      are about the rates at which DNA sequences from different individuals are
      expected to differ. Heterogeneity for such quantities as base composition, or
      lengths between successive subsequences of specified types, may be sufficient to
      account for observed long-range correlations between bases. The need for
      statistical models and analyses of DNA sequence data will continue, and will
      offer interesting challenges.

PMID- 8261260
TI  - Forensic inference from genetic markers.
AB  - This review provides an overview of forensic inference from genetic markers.
      Because the judge and jurors are charged with decision-making, the forensic
      expert's job is to provide a useful summary of the evidence to the court. Hence,
      this review focuses on the likelihood ratio as a means of summarizing the genetic
      data for either criminal or civil cases. The properties of the genetic markers
      frequently used in today's court cases, those being VNTR loci, are discussed in
      detail. Unlike traditional markers, the data from VNTR loci are complicated
      because current molecular methods generate data that follow a finite mixture
      distribution. Critical ancillary issues are also covered, though not in detail.

PMID- 8261261
TI  - Metropolis sampling in pedigree analysis.
AB  - This paper reviews and develops the applications of Markov chain Monte Carlo
      methods in pedigree analysis, with particular stress on the Metropolis algorithm.
      In likelihood based genetic analyses, standard deterministic algorithms often
      fail because of the computational complexity of the observed pedigree data under
      a proposed genetic model. The new Monte Carlo methods permit approximate maximum
      likelihood estimation in the presence of such complexity. Monte Carlo
      implementation of the EM algorithm is the key to successful maximum likelihood
      analysis. Gibbs sampling and the Metropolis algorithm are alternative ways of
      defining Markov chains for performing the E step of the EM algorithm. Two
      applications illustrate the power and simplicity of the Metropolis algorithm. One
      of these applications involves a discrete model for variance component analysis
      of quantitative traits; the other application involves a Monte Carlo version of
      location scores for multipoint linkage analysis.

PMID- 8261262
TI  - Laparoscopic Nissen fundoplication: detailed analysis of 132 patients.
AB  - With the world-wide use of laparoscopy, new applications have been found,
      particularly in the field of esophageal and gastric surgery. From January 1991
      through April 1992, 132 patients underwent laparoscopic Nissen fundoplication.
      The indication for laparoscopic intervention was symptomatic gastroesophageal
      reflux disease (GERD) not responding to medical treatment. The preoperative
      assessment included esophagogastroscopy, barium meal, esophageal manometry, and,
      in selected cases, 24 h pH studies. There was no operative-related mortality. The
      overall morbidity was 7.5%. Ninety-eight patients were seen 3 months after
      surgery and evaluated for control of reflux symptoms. One patient complained of
      mild recurrence of reflux symptoms; however, endoscopic examination revealed no
      evidence of recurrent esophagitis. Three complained of occasional dysphagia and
      two, of mild dysphagia. One individual required reoperation for persistent,
      severe dysphagia. The excellent results observed so far with this procedure have
      led us to believe that laparoscopic Nissen fundoplication is the procedure of
      choice for patients with intractable GERD.

PMID- 8261263
TI  - Transaxillary endoscopic sympathectomy--a report of experience in 150 patients
      with palmar hyperhidrosis.
AB  - We report our 1-year experience with transaxillary endoscopic sympathectomy in
      150 patients with palmar hyperhidrosis (PH). The double-puncture technique of
      video laparoscopy was used in a transaxillary approach to perform the
      sympathectomy by either electrocautery (EC; 93.3%) or electroresection (ER;
      7.7%). The procedure was successfully completed in 299 operated limbs and
      required conversion to open surgery in 1 operated limb because of extensive
      pleural adhesions. The mean operative time of EC was significantly less than that
      of ER. In a total of 29 procedures, there were three technical complications.
      Most patients (92.7%) were discharged after an overnight hospital stay. On the
      seventh postoperative day, the cure rate was 99.3%. During the mean follow-up
      period of 200.1 days, there was no recurrence in 130 patients. Apparent
      compensatory hyperhidrosis occurred in 28 patients (21.5%). In conclusion,
      transaxillary endoscopic sympathectomy offers a simple and effective treatment to
      patients with PH, resulting in a shorter hospital stay and convalescent period.

PMID- 8261264
TI  - The physiology of laparoscopic surgery: pulmonary function after laparoscopic
      cholecystectomy.
AB  - Changes in pulmonary function were studied via standard spirometry in 30 patients
      after laparoscopic cholecystectomy (LC) and compared with those in nine patients
      after traditional open cholecystectomy (OC). Studies performed presurgery and the
      morning after surgery included forced vital capacity (FVC), forced expiratory
      volume in 1 s (FEV1), and forced expiratory flow (FEF25%-75%). Age (43.9 +/- 2.6
      years for LC and 42.3 +/- 3.2 for OC), sex, reasons for cholecystectomy, and
      smoking history were similar in both groups. The mean FVC decreased 23% after LC
      (3.57 +/- 0.18 L presurgery, range 0.56-5.62, versus 2.68 +/- 0.17 postsurgery,
      range 0.65-5.14) and 35.2% after OC (mean 3.52 +/- 0.29 presurgery, range 2.38
      4.99, versus 2.24 +/- 0.24, range 1.23-3.49 postsurgery). FEV1 showed similar
      changes, with LC decreasing pulmonary function by 24.3% (2.76 +/- 0.14 L
      presurgery versus 2.01 +/- 0.12 postsurgery) compared with a 36.2% reduction in
      FEV1 after OC (2.86 +/- 0.29 L presurgery versus 1.81 +/- 0.21 L postsurgery).
      Forced expiratory flow decreased by 24.3% after LC and 40% after OC. Laparoscopic
      cholecystectomy provides less decrement in pulmonary function than traditional
      open cholecystectomy.

PMID- 8261265
TI  - Posterior truncal vagotomy and stapling of the anterior stomach wall in 30
      patients with duodenal ulcer: acid inhibition, gastric emptying, and endoscopic
      dye spraying. Prospects for endoscopic vagotomy.
AB  - The use of a stapling instrument (TA90) to effect a transection of the anterior
      gastric wall with posterior truncal vagotomy but preserving innervation to the
      anterior wall of the antrum for duodenal ulcer is described. The operation
      resulted in the endoscopic healing of all the ulcers; however, recurrent
      ulceration was seen in 3 of 25 patients. Basal acid output was reduced from 7.84
      (SEM 1.73) to 3.49 (SEM 1.15) mmol/h (t = 2.09, df = 15.7, p = 0.05), while peak
      acid output was reduced from 38.67 (SEM 3.11) to 19.26 (SEM 2.3) mmol/h (t =
      5.01, df = 23.9, p = 0.0000). Solid and liquid gastric emptying studies were
      performed, and while some delay in solid emptying was seen, only one patient
      complained of transient gastric stasis. Endoscopic Congo red staining was
      performed postoperatively and a tongue of innervated mucosa along the lesser
      curve was seen in each case. The procedure was easily and rapidly performed, and
      early clinical results are good, with 25 of 30 patients having a good (Visick I)
      result.

PMID- 8261266
TI  - Meralgia paresthetica: a complication of laparoscopic herniorrhaphy.
AB  - Laparoscopic herniorrhaphy is a new and presently evolving technique applied to
      the repair of inguinal defects. Many different authors have described various
      methods by which this can be achieved. Some of these include the transabdominal
      preperitoneal approach, the plug technique, the intraperitoneal onlay of mesh,
      and the extraperitoneal approach. The authors have performed 252 laparoscopic
      hernia repairs utilizing a form of the transabdominal preperitoneal procedure
      that is referred to as the "transperitoneal anatomic approach." The development
      of new procedures or the modification of existing procedures can create new
      problems or alter the pattern of traditional complications. These problems must
      be thoroughly evaluated and reported if repetition of these errors is to be
      avoided. Five cases of meralgia paresthetica are reported that resulted from
      staple entrapment of the lateral femoral cutaneous nerve during laparoscopic
      herniorrhaphy. An understanding of the preperitoneal inguinal anatomy and precise
      placement of staples will allow avoidance of this complication.

PMID- 8261267
TI  - Technique of laparoscopic cholecystojejunostomy with a Roux-en-Y loop.
AB  - In order to avoid laparotomy in patients with biliary obstruction due to
      inoperable carcinoma of the pancreatic head, we evaluated the feasibility of a
      bypass operation using minimal invasive measures. A technique of laparoscopic
      cholecystojejunostomy was tested in adult pigs who had undergone clip occlusion
      of the distal common bile duct to imitate choledochal obstruction. Complete
      biliary bypass was restored with a cholecystojejunostomy via a Roux-en-Y loop
      using two circular staplers (21, 25, or 29 mm diameter), introduced through a
      prototype 33-mm-diameter trocar, used to effect the proximal and distal
      anastomoses. Seven pigs operated on in this way recovered easily, with normal
      weight gain and without technical complications. Contrast radiography of the
      biliary bypass at autopsy on day 28 confirmed patent and leak-free anastomoses
      and functional bypass. We conclude that laparoscopic cholecystojejunostomy with a
      Roux-en-Y loop is a feasible technique and results in an uncomplicated
      postoperative course and a biliary bypass with optimal function. Endoscopic
      application of circular staplers for laparoscopic enterobiliary and enteroenteral
      anastomosis is practical and safe.

PMID- 8261268
TI  - Thoracoscopic sympathectomy.
AB  - With the advent of advanced video and laparoscopic techniques, new applications
      have been found for thoracoscopy's expanding role in thoracic surgery. Described
      herein are three cases of thoracoscopic sympathectomy for three different
      indications. The evaluation and surgical technique are described in detail.
      Thoracoscopic sympathectomy is an excellent alternative to open transthoracic
      approach.

PMID- 8261269
TI  - Indication for thoracoscopic truncal vagotomy.
AB  - Presently, more and more patients are being offered a minimally invasive surgical
      procedure for the management of chronic duodenal ulcer disease. Although previous
      authors have described a variety of laparoscopic selective vagotomy operations
      for this disease, there remains an important role for truncal vagotomy in
      selected patients. Two individuals with long-standing peptic ulcer disease and a
      history of prior perforation underwent thoracoscopic vagotomy. Both patients
      tolerated the surgical procedure well with a rapid return to work/normal
      activity. After 2 years both patients remain asymptomatic.

PMID- 8261270
TI  - Electrohydraulic lithotripsy combined with laparoscopy and endoscopy for managing
      difficult biliary stones.
AB  - Large or impacted bile duct stones can be difficult to manage with endoscopic and
      laparoscopic techniques. Electrohydraulic lithotripsy (EHL) seems to be ideally
      suited for these difficult cases. We report our experience and review the
      literature. Adjunctive use of EHL was attempted in seven patients with
      complicated stones. In six, preoperative endoscopic retrograde
      cholangiopancreatography (ERCP) was unsuccessful. Five were accessed with
      laparoscopic transcystic technique, one by T-tube tract, and one with open common
      bile duct (CBD) exploration. EHL was successful in six. The unsuccessful attempt
      was with a 5-cm CBD stone. No complications of EHL were encountered. In review of
      the literature, we have found 256 cases of biliary lithiasis successfully treated
      with EHL without bile duct perforation. Based on our own experience and review of
      the literature, we conclude that properly used EHL is safe and effective in
      managing complicated biliary lithiasis.

PMID- 8261271
TI  - Mediastinal tumor and application of thoracoscopic surgery.
AB  - Thoracoscopic resection of a mediastinal tumor or cyst was done in three
      patients: two with neurogenic tumors and one with a bronchogenic cyst. The tumors
      and cyst showed evidence of a discrete plane on computed tomography of the chest.
      The mean operation time and estimated blood loss were 156 min and 45 g,
      respectively. For all three patients, the chest drain was removed within 48 h
      after operation, and there were no complications related to thoracoscopic
      surgery. The advantages of this approach are less pain, early return to normal
      activity, and an acceptable cosmetic appearance. Based on our experience,
      thoracoscopic surgery is considered the treatment of choice for certain
      mediastinal tumors or cyst.

PMID- 8261272
TI  - Carbon dioxide embolization and laparoscopic cholecystectomy.
AB  - The risk of venous air or CO2 embolization during laparoscopic biliary procedures
      is unknown. Sixty-one consecutive patients undergoing laparoscopic
      cholecystectomy at La Crosse Lutheran Hospital/Gundersen Clinic were monitored by
      precordial Doppler ultrasound and end-tidal capnography to determine the risk of
      gas embolization. Patients ranged in age from 19 to 77 years (mean, 47 years). No
      venous embolization was detected by Doppler ultrasound or capnography. The
      highest end-tidal CO2 ranged from 34 to 53 mm Hg (mean, 41 mm Hg). No patient
      demonstrated an abrupt change in end-tidal CO2. No significant intraoperative
      hemodynamic changes occurred, and no postoperative neurologic defects developed.
      We caution the surgical community to remain alert concerning the possibility of
      venous gas embolization as newer laparoscopic procedures are developed that may
      have increased risks of embolization.

PMID- 8261273
TI  - Laparoscopic appendectomy: treatment of choice for suspected appendicitis.
AB  - Results and complications in 100 patients treated over a 3-year period with the
      laparoscopic approach for clinically diagnosed acute appendicitis are evaluated.
      They are compared with results and complications in 100 patients with the same
      diagnosis who had been treated with the open technique performed by the same
      surgeon during the same 3 years. The results suggest that laparoscopy provides
      excellent exposure of the appendix regardless of its position. In the absence of
      pathology of the appendix, laparoscopy allows for a thorough examination of the
      entire abdomen and pelvis and good exposure and definitive treatment of most
      surgical conditions encountered. In the event of appendicitis, regardless of its
      severity, laparoscopic appendectomy results in less postoperative pain, shorter
      hospital stays, faster return to normal activities, fewer postoperative
      complications, and superior cosmetic results. Our experience suggests that the
      laparoscopic approach is the best approach to diagnosis and treatment of the
      conditions encountered in patients with suspected appendicitis.

PMID- 8261274
TI  - Laparoscopy in abdominal gunshot wounds.
AB  - The role of laparoscopy in the evaluation of abdominal trauma continues to
      evolve. It has been successfully used in blunt and penetrating trauma. We report
      our experience with diagnostic laparoscopy in 28 patients with abdominal gunshot
      wounds. We found a 100% accuracy and a 0% morbidity in patients with negative
      laparoscopy. We report a case in which laparoscopy was used to demonstrate an
      isolated nonbleeding liver injury due to a gunshot wound to the abdomen.
      Nontherapeutic laparotomy was avoided.

PMID- 8261275
TI  - Avoiding complications with laparoscopic herniorrhaphy.
AB  - Before laparoscopic inguinal hernia repair can be widely adopted, general
      surgeons must become familiar with the laparoscopic presentation of the inguinal
      anatomy and must obtain practice with an effective technique that follows the
      surgical tenets of a good repair. This paper discusses some of the possible
      pitfalls of performing laparoscopic hernia repair and presents recommendations
      for success, including a brief description of a technique that has been used
      successfully in > 60 cases.

PMID- 8261276
TI  - Laparoscopy-assisted aortobifemoral bypass.
AB  - Therapeutic laparoscopy has substantially simplified the postoperative course of
      patients suffering from hepatobiliary, gastric, or colonic disease. One important
      advantage of this modality is the decrease in postoperative pain, which
      diminishes the potential for cardiopulmonary problems. Patients with aortoiliac
      atherosclerotic disease are at high risk for postoperative complications, and a
      minimally invasive procedure may favorably affect their postoperative recovery.
      We describe here the first patient on whom we performed a laparoscopy-assisted
      aortobifemoral bypass. Under the pneumoperitoneum, seven 10-mm trocars were
      inserted to permit aortic dissection and creation of retroperitoneal tunnels to
      the femoral regions. After evacuation of the pneumoperitoneum, an 8-cm midline
      incision was made to allow a side-to-end aortic anastomosis. The patient's
      postoperative period was uncomplicated by any cardiopulmonary problems despite
      his history of three myocardial infarctions; the patient had minimal pain that
      allowed for a quick return to ambulation. This procedure is minimally invasive
      and appeared to simplify the postoperative period in our patient. It could become
      the procedure of choice for certain patients with aortoiliac disease.

PMID- 8261277
TI  - Colocutaneous fistula--a rare complication of percutaneous endoscopic
      gastrostomy.
AB  - Although the percutaneous endoscopic gastrostomy technique for feeding is a
      fairly common procedure now, we have not come across a complication such as
      described below, a probable migration of the tube from the stomach to the colon,
      without any objective proof for this.

PMID- 8261278
TI  - Video-assisted thoracoscopic excision of intrathoracic masses in children: report
      of two cases.
AB  - Video-assisted thoracoscopy was used to remove a bronchogenic cyst in a 6-year
      old boy and a foregut duplication cyst in a 2-year-old girl. Access ports were
      placed along the site of a proposed thoracotomy incision and chest tube exit
      site. Thoracoscopic excision was uneventful, and each child left the hospital on
      the second postoperative day. Video-assisted thoracoscopy has a role in the
      evaluation and the definitive treatment of intrathoracic masses in children.

PMID- 8261279
TI  - Laparoscopic Heller cardiomyotomy and thoracoscopic esophageal long myotomy for
      the treatment of primary esophageal motor disorders.
AB  - The technique of laparoscopic and thoracoscopic esophageal myotomy is described.
      The laparoscopic Heller procedure was performed in a patient with manometrically
      diagnosed achalasia and the thoracoscopic long esophageal myotomy in another with
      diffuse esophageal spasm. Both operations were performed in the same fashion as
      during open surgery, using standard laparoscopic surgical instruments. Antireflux
      procedures using the Dor and modified Belsey fundoplications protected patients
      from iatrogenic reflux. Complete relief of dysphagia in the first case and chest
      pain in the second has been confirmed after 2- and 4-month follow-up,
      respectively. Laparoscopic Heller myotomy and thoracoscopic long esophageal
      myotomy are technically feasible and reduce surgical trauma, hospitalization, and
      postoperative recovery. They offer a viable alternative for the definitive
      management of primary esophageal motor disorders comparable with that of open
      surgery.

PMID- 8261280
TI  - Transport in-vitro fertilization and embryo transfer.

PMID- 8261281
TI  - The case for radiographers performing barium enemas.

PMID- 8261282
TI  - Why radiologists should perform barium enemas.

PMID- 8261283
TI  - Paediatric anaesthetic emergencies.
AB  - There is nowadays virtually no contraindication to anaesthesia for even small,
      sick neonates provided that adequate resuscitation is first carried out.
      Furthermore, apart from severe trauma and airway difficulties, very few
      paediatric surgical emergencies require immediate intervention. Most emergencies
      can be treated within a few hours, preferably when the full facilities of the
      hospital are available.

PMID- 8261284
TI  - Current concepts in the use of intra-aortic balloon counterpulsation.
AB  - Mechanical support of the circulation using intra-aortic balloon counterpulsation
      has thus far largely been confined to cardiac units. With improved techniques of
      insertion, many critically ill patients may now benefit. This article reviews the
      physiology of counterpulsation, the indications and contraindications for its
      use, and the complications that may occur.

PMID- 8261285
TI  - Cystic fibrosis screening strategies.
AB  - Cystic fibrosis is the most common single gene disorder in Western populations.
      With the discovery of the principal genetic mutations responsible for the
      disease, screening has become feasible. The challenge is now to devise an
      effective screening strategy. Various approaches are possible, and each has its
      own merits, but on balance antenatal screening would appear to be the most
      practical.

PMID- 8261286
TI  - Current trends in the management of bacterial meningitis.
AB  - The relevance of the host inflammatory response in the pathophysiology of
      bacterial meningitis is an important new concept. Modulation of this process by
      steroids may significantly affect the prognosis. We examine current trends in the
      clinical management of bacterial meningitis.

PMID- 8261287
TI  - Current state of psychosurgery.
AB  - This article considers aspects of the contemporary practice of psychosurgery in
      Britain including the numbers of operations, operative procedures and the
      assessment and indications for surgery. The evaluation of outcome and possible
      adverse consequences are discussed in the light of some recent research.

PMID- 8261288
TI  - Science and art of diagnosis.
AB  - Diagnosis is the weakest link in the chain of medical services as they are
      practised today. The computer has a major role to play in improving the situation
      and also in encouraging greater patient participation.

PMID- 8261289
TI  - Slides in dermatology: 1.

PMID- 8261290
TI  - The incontinent woman: 1.
AB  - Urinary incontinence is a common condition; however, symptoms often bear no
      relation to the ultimate diagnosis apart from uncomplicated stress incontinence.
      Objective investigation is recommended to establish an accurate diagnosis leading
      to effective treatment.

PMID- 8261291
TI  - Hyperbaric oxygen therapy.

PMID- 8261292
TI  - Molecular genetics of myotonic dystrophy.

PMID- 8261293
TI  - Hyperbaric oxygen therapy.

PMID- 8261294
TI  - Drug-induced parotid swelling.

PMID- 8261295
TI  - Varicocele--a clinical enigma.

PMID- 8261296
TI  - Changes in serum immunosuppressive acidic protein following surgery in patients
      with renal carcinoma.
AB  - Serum immunosuppressive acidic protein (IAP) was measured serially in 69 patients
      with renal carcinoma who were treated surgically and followed up for more than 6
      months after surgery. Elevated IAP levels > 600 micrograms/ml were seen in 8 of
      52 patients without evidence of recurrence and in 5 of 10 patients prior to
      clinical evidence of recurrence but in whom recurrence did eventually develop.
      The positive rate of IAP levels > 600 micrograms/ml in recurrent cases was
      significantly higher than in non-recurrent ones. In 7 patients with distant
      metastases, IAP levels rose to > 500 micrograms/ml in 3 of 5 patients whose
      disease progressed despite therapy; levels fell to < 600 micrograms/ml in 2
      patients who responded to therapy. The data suggest that recurrence should be
      suspected in patients with IAP levels > 600 micrograms/ml, as these changes
      appear to correlate with the response of metastases to therapy.

PMID- 8261297
TI  - Long-term results of pelvic floor training in female stress urinary incontinence.
AB  - One hundred and seventy women with genuine stress urinary incontinence
      participated in a pelvic floor exercise (PFE) programme (duration 4.7 +/- 0.2
      months, range 1-18). Twenty-seven women awaiting surgery for genuine stress
      urinary incontinence constituted the control group. The women were evaluated
      using a provocation test, vaginal palpation and subjective assessment before and
      after treatment. After the PFE programme, 23% of the women considered themselves
      cured, 48% were improved and 29% unchanged. According to the provocation test
      used in this study 64% were cured or improved following PFE. The long-term
      results of PFE were assessed by means of a postal questionnaire 2 to 7 years
      after completion of the supervised training period (response rate 152/170; 89%).
      During this time 38 women (25%) had undergone operative treatment. Of the
      remaining patients, 13 (11%) reported that they were still cured, 50 (44%)
      continued to be improved, 35 (31%) were unchanged and 16 (14%) had deteriorated.
      However, the frequency of PFE training during the follow-up period was
      unsatisfactory, as only 15% were training several times a day. This indicates
      that continued guidance from a physiotherapist could improve the long-term
      efficacy of PFE training.

PMID- 8261298
TI  - The urethral plug II: an alternative treatment in women with genuine urinary
      stress incontinence.
AB  - An improved design of the recently developed urethral plug was evaluated for the
      treatment of women with genuine urinary stress incontinence. The plug consists of
      an oval meatal plate, a soft stalk and 1 or 2 spheres along the stalk with fixed
      distances between the meatal plate and the spheres. Inside the stalk is a
      removable semi-rigid guide pin to ease insertion. Forty women were randomly
      allocated to treatment with either the 2-sphere or the 1-sphere plug during
      period 1 (2 weeks). In period 2 (2 weeks) the patients used the other plug. They
      then continued with what they judged to be the better plug in period 3 (2
      months). Eighteen patients (45%) completed period 3 with the "preference" plug
      and 17 were subjectively and objectively continent or improved. Fourteen of these
      women preferred the 2-sphere device. The plugs were equally effective in patients
      with mild or severe incontinence. To accommodate variations in urethral length
      and to avoid the loss of plugs, the devices are available in different lengths.
      Six women developed urinary tract infections and 2 of these had a plug in the
      bladder. The urethral plug is an effective treatment in a group of women with
      stress incontinence. Removal by hand is advisable in order to avoid retention of
      plugs in the bladder.

PMID- 8261299
TI  - Histopathological changes in Kock pouch.
AB  - To investigate whether tumour recurrence or histological changes occur in the
      Kock pouch, periodic endoscopy with biopsy of the pouch was performed in 15
      patients 6 to 66 months after radical cystectomy and urinary diversion for
      invasive bladder cancer. Endoscopy was undertaken 1 to 4 times in each patient (a
      total of 37 times in all patients). During endoscopy, random biopsies were taken
      from the pouch wall, and from the afferent and the efferent nipples. The
      histological changes were graded as: (1) villous atrophy (grade 0 to 3, 0: nearly
      normal; 1: shortening, villi/crypt of Lieberkuhn [length] between 1.5 and 4.0; 2:
      moderate flattening, villi/crypt < 1.5; and 3: almost complete disappearance of
      villi); (2) fibrosis; and (3) chronic inflammation (grade 0 to 3, based on the
      amount of fibrous tissue and inflammatory cell infiltration in the lamina
      propria, respectively). There was no dysplasia or malignant tumour in the Kock
      pouch in any of the 15 patients. The histology of the ileum changed in terms of
      villous atrophy, fibrosis and chronic inflammation in the lamina propria and
      thickening of the muscularis mucosa. The same grade of villous atrophy of the
      pouch wall, the afferent and the efferent nipples was only found in 3 patients.
      More fibrosis and less chronic inflammation in the lamina propria were found at
      the efferent nipple than at the afferent nipple or pouch wall in 8 patients and 5
      patients, respectively. Thickening of the muscularis mucosa was found in 13 of 15
      patients (86.7%). In conclusion, there was no dysplasia or recurrent tumour in
      the Kock pouch in patients who were followed for up to 66 months. Various grades
      of histological changes of the ileum in terms of villous atrophy, fibrosis and
      chronic inflammation of the lamina propria, and thickening of the muscularis
      mucosa were found in the pouch wall, and in the afferent and efferent nipples.
      More fibrosis and less chronic inflammation were commonly observed at the
      efferent nipple than at the afferent nipple or pouch wall. The degree of
      histological changes varied even among patients followed over the same period
      after operation. The time to progression of villous atrophy also varied. The
      histological changes in some patients were dissimilar even at the same site of
      the Kock pouch.

PMID- 8261300
TI  - Development of a catheterised bladder model to evaluate urinary drainage
      equipment.
AB  - A catheterised bladder model was developed to examine the design features of
      urinary drainage bags. The drainage bag of 4 commonly used products was
      inoculated with either Escherichia coli or Proteus mirabilis. The speed of
      retrograde contamination towards the "bladder" was determined over 96 h. The
      effect of lifting the drainage bag above the level of the "bladder" was examined
      also. Within 4 days micro-organisms were detected in the backflow valves/drip
      chambers of all products, but contamination had not progressed as far as the
      catheter. Ps. mirabilis appeared to migrate more rapidly than Esch. coli. Lifting
      the drainage bag had no effect on the migration of either organism. The
      implications of these results for clinical practice are discussed.

PMID- 8261301
TI  - Superficial bladder cancer: timing of check cystoscopies in the first year.
AB  - We report a prospective study of 141 patients presenting for the first time with
      a small, solitary, non-invasive, moderately or well differentiated transitional
      cell carcinoma of the bladder. The pattern of recurrence in the first year was
      assessed and recurrence rates calculated; 80% of patients without recurrence at 3
      months remained clear in the first year. There was a highly significant reduction
      in recurrence rates for those free of recurrence at 3 months. It has been
      suggested that this group should have the second check cystoscopy at 1 year and
      yearly cystoscopies thereafter. Our findings support that proposal.

PMID- 8261302
TI  - Does flexible cystoscopy miss more tumours than rod-lens examination?
AB  - The first blind, prospective, randomised comparison of flexible cystoscopy with
      rod-lens cystoscopy was carried out on 53 consecutive volunteers with bladder
      tumours or haematuria. Three patients' recurrences were missed on flexible
      cystoscopy and 3 others on rod-lens examination. It was expected that the 9% rate
      of missed tumours would lessen with increased experience of flexible cystoscopy,
      as 2 of them occurred in the first 12 examinations and all of the lesions missed
      were < 5 mm in diameter. Rod-lens cystoscopy, the accuracy of which appears to
      have been measured for the first time, was no more sensitive.

PMID- 8261303
TI  - Proliferation indices as independent prognostic factors in papillary Ta-T1
      transitional cell bladder tumours.
AB  - A cohort of 148 patients with papillary Ta-T1 transitional cell carcinomas (TCCs)
      was followed up for over 10 years and flow cytometric (DNA ploidy, S phase
      fraction) and morphometric variables (5 nuclear factors, volume corrected mitotic
      index) were related to prognosis during this period. Recurrence-free survival was
      significantly related to DNA ploidy, S phase fraction and M/V index. Progression
      in T-category was predicted by M/V index, S phase fraction, DNA ploidy and WHO
      grade. The same variables predicted progression in N- and M-categories. In a
      multivariate analysis only M/V index and S phase fraction were independent
      predictors of progression. Univariate analysis showed that M/V index, SPF, DNA
      ploidy and WHO grade predicted survival. In a multivariate survival analysis only
      M/V index and SPF were independent predictors. The results showed that
      proliferation indices had independent prognostic value in papillary Ta-T1 TCCs
      and the grading of these tumours could be based on the proliferation indices.
      Papillary Ta-T1 tumours with a M/V index value < or = 10/mm2 or SPF < or = 10%
      had a favourable prognosis whereas tumours with M/V index > 10/mm2 or SPF > 10%
      had a high malignant potential.

PMID- 8261304
TI  - Uraemia with concomitant urothelial cancer.
AB  - We report our experience with 3 uraemic patients who were found to have
      transitional cell carcinoma of the renal pelvis, ureter and urinary bladder after
      undergoing haemodialysis for an average of 18 months (range 11-28). The
      underlying causes of renal failure were chronic glomerulonephritis or
      pyelonephritis. Bloody urethral discharge was the cardinal symptom. Because of
      anuria, it was often discovered at a late stage. In spite of their poor general
      condition and advanced stage, palliative surgical intervention was still
      performed. After a mean follow-up of 9 months, progression of disease was noted
      in 1 patient. The importance of regular follow-up in patients with end-stage
      renal disease for early detection of concomitant cancer cannot be over
      emphasised. Uraemic patients with urothelial cancer should be treated in the same
      way as non-uraemic patients, since aggressive surgical intervention may improve
      their quality of life and prolong their survival.

PMID- 8261305
TI  - Prostatic sarcoidosis. Review of genitourinary sarcoidosis.
AB  - Sarcoidosis is seen by the urologist only rarely but it may present a diagnostic
      and therapeutic dilemma. We describe a rare case of prostatic sarcoidosis. The
      literature relating to sarcoidosis throughout the genitourinary system is
      reviewed.

PMID- 8261306
TI  - Audit and its impact in the management of advanced prostatic cancer.
AB  - From a prospective database of 614 consecutive men with newly diagnosed prostatic
      cancer an audit of outcome was studied in 169 men who presented with bone
      metastases and subsequently received hormonal manipulation in the form of
      monotherapy. The cohort was divided into 2 groups according to serum alkaline and
      acid phosphatase enzyme levels. Men with normal alkaline phosphatase levels
      (41.5%) had a better prognosis (median survival 38 months) than those with
      elevated levels at presentation (58.5%) (median survival 19 months). This
      difference was highly significant. A similar stratification on prostatic acid
      phosphatase levels did not yield any prognostic significance. With regard to
      cause-specific survival, serum alkaline phosphatase was an even more powerful
      prognosticator, with a median survival of 45 and 21 months for patients with
      normal and elevated levels respectively. Thus monotherapy is recommended for
      metastatic prostate cancer patients with normal serum alkaline phosphatase, but
      for those with elevated alkaline phosphatase the alternative avenues of treatment
      must be explored.

PMID- 8261307
TI  - Deoxyribonucleic acid histogram of testes in primary transsexualism.
AB  - The influence of oestrogen on spermatogenesis was evaluated by comparing its
      effect on the testes of primary male transsexuals and those who had undergone
      hormone therapy for prostatic carcinoma. Eight primary transsexuals were studied.
      They had been diagnosed on clinical and psychiatric evidence and had been on
      oestrogen therapy for several years since puberty. Histological sections of
      testicular tissue obtained at reassignment surgery from 8 phenotypic male
      transsexuals (aged 24-32 years) with an XY chromosome complement were studied by
      light microscopy. The formalin-embedded specimens were analysed by flow cytometry
      for deoxyribonucleic acid (DNA) histograms. Both the histology and DNA histograms
      revealed a pattern of maturation arrest in 12 of 16 testes in which the diploid
      cell compartment occupied most of the spermatogenetic element, followed by
      tetraploid and monoploid cells. Two testes showed impaired spermatogenesis and 2
      were normal. The DNA histograms and pathology were also evaluated in 20 testes
      after 3 to 8 years of hormone therapy in patients with advanced prostatic
      carcinoma (aged 60-78 years). No maturation arrest was found in these patients.
      Sixteen of them had a pattern of fibrosis and atrophy and 4 had impaired
      spermatogenesis. It was concluded that oestrogen influenced spermatogenesis and
      affected the maturation of spermatogonia mostly during puberty.

PMID- 8261308
TI  - Chemical analysis of post-lithotripsy stone fragments: a critical evaluation.
AB  - A scheme for the chemical microanalysis of renal stone fragments recovered from
      urine voided immediately after lithotripsy has been developed and evaluated. The
      analytical procedure includes assay of calcium, magnesium, phosphate, oxalate and
      urate and has been applied to 78 such urine samples. Problems relating to co
      existing crystalluria and blood and urine contaminants have been recognised and
      overcome. However, significant loss of all stone components due to fragment
      dissolution in urine prior to recovery was found to occur and was investigated.
      The distribution of stone components found in these analyses was similar to that
      seen in previous surveys of intact stones.

PMID- 8261309
TI  - Prolapse of the urethral mucosa in prepubertal West Indian girls.
AB  - Forty-two cases of urethral mucosal prolapse were reviewed in Trinidad, West
      Indies. The main presenting symptom was vaginal bleeding; 31% of patients had
      associated infection and 97% belonged to social classes III to V; 33% had
      conservative management and 67% had surgical treatment. It was concluded that
      treatment should be medical rather than surgical and it is suggested that this is
      a disease of the low socio-economic group.

PMID- 8261310
TI  - Genuine stress incontinence induced by prazosin.

PMID- 8261311
TI  - Metastasis to skin from Leydig cell tumour.

PMID- 8261312
TI  - Bladder carcinoma in a renal transplant patient.

PMID- 8261313
TI  - Giant ancient schwannoma of the urinary bladder presenting as a pelvic mass.

PMID- 8261314
TI  - Primary adenocarcinoma of the seminal vesicle.

PMID- 8261315
TI  - Polyorchism.

PMID- 8261316
TI  - Vasitis nodosa due to torture.

PMID- 8261317
TI  - Paper colic.

PMID- 8261318
TI  - The use of vapocoolants for detumescence.

PMID- 8261319
TI  - "Extraperitoneal" ileocystoplasty.

PMID- 8261320
TI  - Tri-radiate incision approach for renal carcinoma invading the thoracic inferior
      vena cava.

PMID- 8261321
TI  - Malignant sphincter stricture treated by a permanent indwelling stent.

PMID- 8261322
TI  - Steel knives and iron lungs: medical instruments as medical history.

PMID- 8261324
TI  - Scholarship in the history of medical technology.

PMID- 8261323
TI  - Bigger than a bread box: medical buildings as museum artifacts.

PMID- 8261325
TI  - Introduction: a brief report on the history of medical collections.

PMID- 8261326
TI  - The role of instruments in the study of Greco-Roman surgery.

PMID- 8261327
TI  - Learning from the artifact: surgical instruments as resources in the history of
      medicine and medical technology.

PMID- 8261328
TI  - Chicago surgical instrument makers, 1855-1899: a directory of makers and
      commentary on historical sources.

PMID- 8261329
TI  - Do you have a latex protocol?

PMID- 8261330
TI  - Expanded role of the operating room nurse in the perioperative practice setting.

PMID- 8261331
TI  - Characterization of the cell wall of Butyrivibrio species.
AB  - Most Butyrivibrio strains have been isolated from the gastrointestinal tract of
      animals and have been classified as Butyrivibrio fibrisolvens. A few strains
      isolated from human feces are designated as Butyrivibrio crossatus, the other
      species in this genus. Butyrivibrio fibrisolvens strains are anaerobic, curved
      rods that produce butyrate, but numerous studies have shown that these strains
      display considerable variations in phenotypic properties and heterogeneity in DNA
      relatedness. Although over 60 strains have been characterized in these respects,
      the cell wall structure of only a few strains has been studied. In this study,
      cell wall related properties of 12 strains representative of five DNA relatedness
      groups were examined. All strains were very sensitive to penicillin and other
      antibiotics that interfere with cell wall synthesis. Although an occasional
      resistant strain was found, most strains were sensitive to a variety of protein
      synthesis antibiotics that included aminoglycosides and tetracycline. In
      contrast, all strains were highly resistant to nalidixic acid. Peptidoglycans
      were isolated from seven B. fibrisolvens strains and Lachnospira multiparus.
      Compositional analyses indicated molar ratios of 0.7:2:2:1:0.8 for muramic acid,
      glucosamine, alanine, glutamic acid, and diaminopimelic acid, respectively, in
      all peptidoglycans, which also showed a low degree of cross-linking. A
      trichloroacetic acid extractable galactosamine-containing polysaccharide
      copurified with the Butyrivibrio peptidoglycans. Electron microscopy of thin
      sections showed all strains to possess a Gram-positive type of cell wall that was
      atypically thin (12-18 nm). Most strains also displayed external (surface)
      polysaccharide layers. Cytoplasmic inclusions and granules were evident in many
      strains and were composed of polysaccharides, on the basis of cell composition
      analyses. The findings that Butyrivibrio strains have overall similarities in
      cell wall properties, but differences in DNA relatedness, suggest that these
      organisms should be classified as several more species in the same genus or
      family.

PMID- 8261332
TI  - Analysis of ploidy and sexual characteristics of natural isolates of Cryptococcus
      neoformans.
AB  - We report here an extensive examination of the ploidy of a basidiomycetous yeast.
      The ploidy of 34 strains of Cryptococcus neoformans var. neoformans, isolated
      mostly from Japanese patients, was determined by means of quantitative
      fluorescence microscopy after DNA staining with propidium iodide. The sexual
      characteristics of the strains including the two tester strains were as follows.
      Twenty-four strains were of the heterothallic alpha type, 1 was of the
      heterothallic a type, and 2 were self fertile; the remaining 7 showed no sexual
      response. The following strains were found to be haploid: the heterothallic a
      strain, 20 of the 24 heterothallic alpha strains, and 3 of the 7 asexual strains.
      Thus, the C. neoformans strains were mostly haploid, as the sexual response of
      this organism suggests. Both of the self-fertile strains and four of the seven
      asexual strains were diploid. Unexpectedly, 4 of the 24 heterothallic alpha
      strains were diploid.

PMID- 8261333
TI  - Yeasts and coliform bacteria of water accumulated in bromeliads of mangrove and
      sand dune ecosystems of southeast Brazil.
AB  - Yeasts and coliform bacteria were isolated from water that accumulated in the
      central cups and adjacent leaf axilae of two bromeliads, Neoregelia cruenta of a
      coastal sand dune and Quesnelia quesneliana of a mangrove ecosystem near the city
      of Rio de Janeiro, Brazil. The mean total coliform counts were above 10,000 per
      100 mL for waters of both plants, but the mean fecal coliform counts were only 74
      per 100 mL for Q. quesneliana and mostly undetected in water from N. cruenta. Of
      90 fecal coliform isolates, 51 were typical of Escherichia coli in colony
      morphology and indol, methyl red, Volges-Proskauer, and citrate (IMViC) tests.
      Seven representatives of the typical E. coli cultures were identified as this
      species, but the identifications of nine other coliform bacteria were mostly
      dubious. The yeast community of N. cruenta was typical of plant surfaces with
      basidiomycetous yeasts anamorphs, and the black yeast Aureobasidium pullulans was
      prevalent. Quesnelia quesneliana had a substantial proportion of ascomycetous
      yeasts and their anamorphs, including a probable new biotype of Saccharomyces
      unisporus. Our results suggested that the microbial communities in bromeliad
      waters are typically autochtonous and not contaminants.

PMID- 8261334
TI  - Two-dimensional electrophoresis method used for determination of plasmid profiles
      of Escherichia coli isolated from a sewage treatment plant.
AB  - The plasmid contents of 306 strains of Escherichia coli isolated from raw and
      treated sewage from a treatment plant as well as from the water 1 km downstream
      were determined. The number and molecular weight of plasmids isolated from a
      representative sample of these strains were also measured. It was observed that
      biological treatment did not significantly alter these parameters. In contrast,
      statistically significant differences in plasmid number and size were observed
      when strains from sewage (raw and treated) were compared with strains isolated
      from brackish water. In raw and treated sewage, more than 96% of the strains
      contained plasmids, compared with 85% in brackish water. Nine to 13% of the
      strains from sewage contained plasmids with more than 56 kilobases, while only 5%
      of the strains from brackish water reached this size.

PMID- 8261335
TI  - Young practitioners in Quebec.

PMID- 8261336
TI  - Euthanasia, physician-assisted suicide.

PMID- 8261337
TI  - Sentence: education in ethics.

PMID- 8261338
TI  - Follow-up endoscopy.

PMID- 8261339
TI  - Gun ownership and crime.

PMID- 8261340
TI  - Gun ownership and crime.

PMID- 8261341
TI  - Gun ownership and crime.

PMID- 8261342
TI  - Gun ownership and crime.

PMID- 8261343
TI  - Blood lead in children.

PMID- 8261344
TI  - Misuse of laxatives.

PMID- 8261345
TI  - The literary horrors of childhood.

PMID- 8261346
TI  - The duty to warn in the Canadian context.

PMID- 8261347
TI  - Confidentiality and the duty to warn.

PMID- 8261349
TI  - Preventive practice among primary care physicians in British Columbia: relation
      to recommendations of the Canadian Task Force on the Periodic Health Examination.
AB  - OBJECTIVES: To compare the current practice of preventive medicine in British
      Columbia with the recommendations of the Canadian Task Force on the Periodic
      Health Examination. Four common, preventable forms of cancer (cervical, breast,
      lung and colorectal) were used as sentinel conditions. DESIGN: Random sample
      mailed survey. SETTING: Private primary care practices in British Columbia.
      PARTICIPANTS: A sample of 300 primary care physicians in 1991; of 285 eligible
      physicians 185 (65%) responded. OUTCOME MEASURE: Compliance with preventive
      practices recommended by the task force. RESULTS: Preventive practice complied
      with the task force's recommendations for breast examinations, mammography,
      cervical smears and initial counselling against smoking; over 90% of the
      physicians performed these manoeuvres in all or most cases. However, less than
      half performed two recommended manoeuvres for all or most patients who smoke:
      advice to follow a diet high in beta-carotene (reported by 10%) and scheduling of
      follow-up visits to reinforce antismoking counselling (by 46%). Most of the
      physicians stated that they perform preventive manoeuvres in the context of an
      annual general physical examination rather than integrating them into routine
      patient care. CONCLUSIONS: The task force's carefully constructed recommendations
      are incompletely followed. Overall, there appears to be a high level of
      compliance with traditional and recommended manoeuvres but also widespread
      persistence in performing traditional manoeuvres no longer recommended and
      failure to adopt new recommendations.

PMID- 8261350
TI  - Learning from rats to reduce people's desire for alcohol.

PMID- 8261348
TI  - Appropriate uses of fluorides for children: guidelines from the Canadian Workshop
      on the Evaluation of Current Recommendations Concerning Fluorides.
AB  - OBJECTIVE: To prevent fluorosis caused by excessive fluoride ingestion by
      revising recommendations for fluoride intake by children. OPTIONS: Limiting
      fluoride ingestion from fluoridated water, fluoride supplements and fluoride
      dentifrices. OUTCOMES: Reduction in the prevalence of dental fluorosis and
      continued prevention of dental caries. EVIDENCE: Before the workshop, experts
      prepared comprehensive literature reviews of fluoride therapies, fluoride
      ingestion and the prevalence and causes of dental fluorosis. The papers, which
      were peer-reviewed, revised and circulated to the workshop participants, formed
      the basis of the workshop discussions. VALUES: Recommendations to limit fluoride
      intake were vigorously debated before being adopted as the consensus opinion of
      the workshop group. BENEFITS, HARMS AND COSTS: Decrease in the prevalence of
      dental fluorosis with continuing preventive effects of fluoride use. The only
      significant cost would be in preparing new, low-concentration fluoride products
      for distribution. RECOMMENDATIONS: Fluoride supplementation should be limited to
      children 3 years of age and older in areas where there is less than 0.3 ppm of
      fluoride in the water supply. Children in all areas should use only a "pea-sized"
      amount of fluoride dentifrice no more than twice daily under the supervision of
      an adult. VALIDATION: These recommendations are almost identical to changes to
      recommendations for the use of fluoride supplements recently proposed by a group
      of European countries. SPONSORS: The workshop was organized by Dr. D. Christopher
      Clark, of the University of British Columbia, and Drs. Hardy Limeback and Ralph
      C. Burgess, of the University of Toronto, and funded by Proctor and Gamble Inc.,
      Toronto, the Medical Research Council of Canada and Health Canada (formerly the
      Department of National Health and Welfare). The recommendations were formally
      adopted by the Canadian Dental Association in April 1993.

PMID- 8261351
TI  - High-density-lipoprotein cholesterol and atherosclerosis.

PMID- 8261352
TI  - Curbing smoking by women, children among challenges facing antitobacco lobby.

PMID- 8261353
TI  - MDs call for more study before endorsing dentists' new recommendations on
      fluoride.

PMID- 8261355
TI  - Is the CNS as house staff an option?

PMID- 8261354
TI  - Is heart transplantation a wise use of scarce health care dollars?

PMID- 8261356
TI  - The role of the nurse in childbirth: perceptions of the childbearing woman.
AB  - The purpose of this descriptive study was to describe the perceptions of
      childbearing women regarding the nurse's role during childbirth. A convenience
      sample of 26 married primiparous mothers experiencing uncomplicated vaginal
      births participated in interviews conducted within two weeks of childbirth.
      Descriptive content analyses were completed. Participants expressed satisfaction
      with nursing care, reporting that they were not aware of how much nurses really
      do. They described the competence of the nurses, the broad range of skills they
      possessed, and the high level of responsibility demonstrated. Domains of nursing
      support identified by these women included: emotional support, information
      support, and tangible support. This study will promote sensitive caregiving in
      order to meet more effectively the needs of the childbearing woman, thus
      promoting more positive childbirth outcomes.

PMID- 8261357
TI  - Case management revisited.

PMID- 8261358
TI  - The CNS as trauma case manager: a new frontier.
AB  - The care of the trauma patient requires highly specialized skills to meet the
      clinical and financial challenges that face the health care practitioner caring
      for this patient population. The role of the trauma case manager in a community
      hospital setting incorporates the roles of expert clinician, educator,
      consultant, researcher, and manager into daily practice utilizing a
      multidisciplinary care delivery process. This process provides the link between
      quality of care and cost-effective care. Trauma case management is an ideal role
      for a CNS.

PMID- 8261359
TI  - Case management: development of a model.
AB  - Case management is the health care delivery model for the 1990s, answering the
      demands for provision of high quality care in a cost-effective manner. The CNS
      will play a pivotal role in the planning, development, implementation, and
      evaluation of a case management model. This article discusses practical aspects
      to consider when developing a case management model that meets the needs of a
      specific institution.

PMID- 8261360
TI  - Divided interests: research versus clinical interviews.

PMID- 8261361
TI  - The nurse clinician: role conflict in research.
AB  - In a recent pilot study focusing on stroke rehabilitation, four clinical nurse
      specialists (CNSs) experienced role conflict when assuming the nurse researcher
      interviewer role. Presenting an overview of the pilot study and the experiences
      that occurred, the authors question the reliability of the interviews. They
      propose that outcomes of research can be biased by role conflict when CNSs serve
      as interviewers and collect data. The authors suggest that interviewing training
      specifically address role conflict.

PMID- 8261362
TI  - Doing it more easily.

PMID- 8261363
TI  - Enhancing staff nurses' interpersonal skills: theory to practice.
AB  - Nurses working with psychiatric-mental health patients require a repertoire of
      skills to assess patient behavior and needs, design creative interventions, and
      evaluate care. The work of interpersonal psychiatric nursing exists within the
      therapeutic relationship between nurse and patient. A coordinated series of
      classes and clinical supervision sessions that present an approach to psychiatric
      nursing care using three major themes of Peplau's model: learning acquisition,
      language competencies, and anxiety reduction are described. Clinical supervision
      was strongly encouraged for participants and one clinical supervisor decided to
      model supervisory sessions using elements of Peplau's theory. Utilizing selected
      aspects of Peplau's interventional techniques during clinical supervision and
      reflecting on the experience provided an opportunity to validate and integrate
      new knowledge and skills. Nurses who sought supervision thus had the advantage of
      experimental learning through participation in clinical supervision.

PMID- 8261364
TI  - The spirit of the place.

PMID- 8261366
TI  - Approaching an age of perfection.

PMID- 8261365
TI  - Legislative and regulatory update: DEA registration for midlevel practitioners.

PMID- 8261367
TI  - Application of empowerment theory for CNS practice.
AB  - Power is necessary for the clinical nurse specialist (CNS) to successfully
      conduct objectives of practice in bureaucratic hospital settings. To obtain
      power, the CNS could use strategies of an empowerment theory to fully
      operationalize roles in hospitals. This article will discuss how the CNS may be
      empowered utilizing strategies in four empowering categories. In addition, the
      many benefits of empowering the CNS are reviewed.

PMID- 8261368
TI  - An intrapreneurial approach to foot care.
AB  - Continual maintenance of an intrapreneurial foot care clinic has proven to be
      challenging and financially rewarding for two gerontological CNSs who designed
      and implemented the clinic. The foot care clinic has been in operation for over
      three years, and is now considered a part of the routine health services offered
      to patients in a large, university-based, ambulatory care clinic.

PMID- 8261369
TI  - Potential liability in good consultative practice.

PMID- 8261370
TI  - Nurse consultant and professional liability.
AB  - The expanded role of nurse consultant brings greater responsibility and risk of
      professional liability in a litigious society. The nurse consultant needs to be
      aware of the elements that constitute malpractice and be able to plan for the
      management of risks involved. When purchasing a liability policy, the nurse
      consultant must consider the practice setting, types of policies, components of
      the policy, cost, and means to obtain adequate coverage. Other strategies for
      protection include proper use of the consultant process, client communication,
      and individualized client contracts. A well-written contract serves as a legal
      document to delineate responsibilities and outcomes, provide a professional
      image, and protect against possible negative developments.

PMID- 8261371
TI  - Helping people help themselves.
AB  - With the growing consumer participation movement and the emphasis in health care
      shifting from hospital to community, the term community development is cropping
      up more and more. Yet the concept of community development has always been
      integral to public health nursing. Simply put, community development is a process
      by which a community identifies its needs and assumes ownership of decision
      making and subsequent action surrounding those needs. By integrating community
      development principles into their work with two neighboring communities, nurses
      with Calgary Health Services facilitated the establishment of a much-needed
      parent support group.

PMID- 8261372
TI  - Needlestick injuries: the shock and reality.
AB  - It has been a typically busy Saturday night in the emergency department. Then,
      near midnight, a trauma casualty was admitted and an incident occurred that would
      occupy Suzanne Smith's thoughts for months to come. When starting an intravenous
      line on this patient, Suzanne spiked herself with a needle. Later the patient was
      taken to the intensive care unit and placed on a ventilator. Suzanne was overcome
      with fear that she might have contracted AIDS. Her fears intensified when she
      learned that the patient, Mr. Norman, was a heroin addict.

PMID- 8261373
TI  - A deadly design.
AB  - On September 30, 1991, registered nurse Bev Holmwood sustained a needlestick
      injury while working in a Vancouver Island operating room. Just over two months
      later she died, the result of hepatitis C she contracted during the accident. Her
      story is a sad reminder of what research has already shown: Sharps injuries are
      the single greatest cause of serious, and often deadly, infection among nurses
      and other health care workers.

PMID- 8261374
TI  - Taking the jab out of needles.
AB  - Typically, health professionals regard injections and venipuncture as routine for
      them and a minor nuisance for the patient. Yet for others, needles arouse dread
      and anxiety. This fear of needles may even lead some people to avoid dental and
      health care.

PMID- 8261375
TI  - [Cooperation. Education/clinical practice in primary health care, in Dakar].
AB  - Senegal recognizes universal health care for all, with health care policies that
      give priority to low income rural neighborhoods and maternal/child health.
      However, the reality is that official health care services cover only 13 per cent
      of the rural population. A collaborative program between the University of
      Montreal School of Nursing and the Centre for Higher Education in Dakar Senegal,
      illustrates the innovativeness of international co-operation. The goal of the
      program is to provide nursing education for students in primary health care and
      midwifery. The nursing students in this program would care for the residents of
      the town of Tivaouane, with emphasis on maternal/child health care. Nursing
      students from three schools in Dakar completed the clinical phase of the program
      working with health care professionals and the residents of Tivaouane. The
      program has four components: education, clinical, research and women's health.
      The education component consists of a revision of the current nursing program, a
      primary health care curriculum, and continuing education for instructors and
      health care personnel. The clinical component gives students the opportunity to
      provide hands on primary health care in Tivaouane. The research component
      includes the development of instruments to identify educational and health care
      needs. The fourth component includes educational activities relating to women's
      health.

PMID- 8261376
TI  - [Orem's family evaluation].
AB  - Nurses are beginning to realize that clients' deficits influence family members
      and, conversely, that family members play an important role in the development
      and resolution of these deficits. The authors attempted to find published
      literature describing a family nursing evaluation based upon Orem's conceptual
      framework. Previous nursing research has described how Orem's model is applied to
      nursing interventions with individual clients, but none has addressed the
      application of nursing interventions to multiperson units within a family
      situation. The authors developed their own concept from their personal and family
      experiences and a theoretical background of Orem's model. They chose to integrate
      systemic and communication theory, and developmental and functional approaches
      with Orem's concept of nursing care of multiperson units. According to the
      authors, this approach is consistent with Orem's model and represents a holistic
      vision of the family. Orem emphasizes that the nurse intervening with multiperson
      units should understand the structure and function of groups and be able to
      identify the actual ongoing process. Although Orem's theoretical framework is not
      based upon a systemic approach, the authors believe that it is possible to blend
      the systemic theory concepts with Orem's model. This article reviews the three
      basic concepts found within Orem's conceptual framework: self-care; self-care
      deficit, and nursing systems. The authors also outline their theoretical
      assumptions for the use of this approach with family nursing interventions, based
      upon six functional dimensions of the family as described by Epstein et al. and
      Guttman. In addition, the article provides a concrete example of how nursing
      evaluation can be structured within this scheme of reference.

PMID- 8261377
TI  - Professional misconduct proceedings.

PMID- 8261378
TI  - Too quick to label sick.

PMID- 8261379
TI  - From autistic to lead toxic.

PMID- 8261380
TI  - More than a wing and a prayer.

PMID- 8261381
TI  - Wielding the shield.

PMID- 8261382
TI  - A statewide breast cancer screening project.
AB  - The cause of breast cancer remains unknown. Because prevention is not an option,
      early detection is the most viable alternative for decreasing the mortality rates
      from breast cancer. To promote early detection, the Arkansas Division of the
      American Cancer Society implemented a project aimed at increasing public
      awareness. The project used a three-pronged approach: the life-saving benefits of
      mammography, regular breast examination by a health-care professional, and the
      importance of regular breast self-examination (BSE). This article focuses on the
      third prong, BSE. Project members recruited and trained 408 BSE instructors in
      the MammaCare method of BSE and contacted a total of 87,141 Arkansas women about
      breast cancer and the importance of early detection. In a follow-up survey of
      1,300 women, of the 198 (15%) who returned the surveys, two women reported
      finding lumps that were diagnosed as cancer.

PMID- 8261383
TI  - Long-term survivors of breast cancer. A qualitative descriptive study.
AB  - The purpose of this study was to explore the daily lived experience of women who
      have survived breast cancer beyond 5 years without recurrence. A qualitative
      descriptive approach was used to collect and analyze the stories of 25 women, 40
      78 years of age, with 5-26 years of survival time. Informants participated in
      three interviews that were transcribed and analyzed. Informants described "going
      through" a survival process that involved movement through several phases. The
      phases included interpreting the diagnosis, confronting mortality,
      reprioritizing, coming to terms, moving on, and flashing back. Phases were
      interpreted within the context of informants' backgrounds, sources of meaning,
      and explanatory models of understanding illness. Many informants described the
      emergence of a more authentic self as a result of the cancer experience. Many
      informants emerged from the cancer experience with a clearer sense of self,
      gratitude for life, and strength and confidence in their ability to manage life
      crises. Findings suggest that care might best be provided by understanding the
      context of each person's life.

PMID- 8261384
TI  - Ifosfamide. Patient care management.
AB  - Ifosfamide is an antineoplastic drug with efficacy and activity in numerous
      cancers. This drug can be administered safely in a hospital setting if toxicities
      and side effects are monitored frequently by a well-informed and educated nursing
      staff. Problems may occur in any bodily system, such as the kidney, central
      nervous system (CNS), gastrointestinal tract, and bone marrow. This article
      reviews appropriate ways to monitor for complications and plan correct nursing
      interventions. Ifosfamide (Ifex, Mead Johnson) is an alkylating agent that is not
      cell cycle specific. One of its metabolites, acrolein, is responsible for
      hematuria. Concurrent administration of mesna (Mesnex, Mead Johnson) is used to
      prevent this complication. The metabolite chloroacetaldehyde may be responsible
      for CNS toxicities. When kidney function and electrolytes are within normal
      limits and psychotropic medications are not given concomitantly, this rarely
      occurs. Gastrointestinal toxicities are usually not severe, but may include
      occasional nausea and vomiting. Hematologic toxicity includes platelet-sparing
      myelosuppression, which can be successfully supported with the administration of
      growth factors.

PMID- 8261386
TI  - Acute and long-term effects of radiation therapy to the eye in children.
AB  - The goal of radiation therapy in pediatric cancer is to destroy cancer cells and
      preserve functional surrounding normal cells. Although all radiation for
      pediatric cancers does not result in complications of the eye, acute and long
      term radiation effects can occur after treatment. Acute radiation effects to the
      eye include erythema, epilation, conjunctivitis, dermatitis, keratitis, corneal
      ulceration, iritis, and retinal edema. Long-term radiation effects include tissue
      necrosis, decreased tear production, telangiectasia, scleral melting, cataract,
      corneal neovascularization, radiation retinopathy, retarded bone growth (of bones
      within the irradiated field), and radiation-induced cancers. Nursing
      interventions and implications will be presented in conjunction with medical
      management for each of these acute and long-term effects.

PMID- 8261385
TI  - Management of acute radiodermatitis. Pharmacological or nonpharmacological
      remedies?
AB  - The medical and nursing literature suggests a wide variety of pharmacological and
      nonpharmacological approaches to treatment of acute radiation skin damages
      (erythema, dry and moist desquamation, ulceration), but no specific and
      standardized therapy. The incidence of radiodermatitis has decreased with mega
      voltage instruments, but it can nevertheless influence the therapeutic program
      and impair quality of life of patients. A study has been conducted to evaluate
      the tolerability and effectiveness of a nonpharmacological remedy, a mixture of
      hydrophobic (stearic acid) and hydrophilic (propylene glycol, glycerol, and
      polyunsaturated alcohols) components in a foam emulsion for the treatment of
      acute skin injuries following radiotherapy. Thirty-eight of 42 initial patients
      were evaluable: we observed a complete response in 22 (57.9%), improvement in 14
      (36.8%), and failure in only two (5.3%).

PMID- 8261387
TI  - Concerns of families in which one member has head and neck cancer.
AB  - This descriptive/exploratory study examined the concerns of families of patients
      with head and neck cancer. A convenience sample from a metropolitan hospital
      included four families. Data were collected through semistructured interviews,
      observations, and chart reviews over three time periods (before treatment, during
      treatment, and during rehabilitation) over a period of 5 months. Analysis of data
      showed five major types of concerns: cancer and its meaning, social relations,
      experience with hospitalization, treatment, and future placement. Findings showed
      that the types of concerns related to head and neck cancer are perceived as
      threatening and harmful. Concerns among patients were different from those of
      their family members across the different time periods. Our findings are useful
      in helping nurses understand the experience of head and neck cancer from the
      perspectives of the patient and their family members, and impact on their
      successful adjustment.

PMID- 8261388
TI  - Application of primary nursing within a team setting in the hospice care of
      cancer patients.
AB  - A qualitative study was conducted to obtain a deeper understanding of the hospice
      care of terminally ill cancer patients, where care was delivered via a primary
      nursing system combined with a team setting. Relatives of terminally ill cancer
      patients (n = 20) and the personnel (n = 8) participated in open-ended
      interviews. Phenomena relating to the philosophy of primary nursing and the
      hospice movement (continuity; closeness; accountability 24 h/day; individualized
      care; satisfied physical, psychological, social, and spiritual needs; and support
      to relatives) were experienced by the relatives, nurses, and physician as "good
      care." Most of the phenomena defined as important needs by the relatives and
      personnel were met when the primary nurse was on duty and the team was intact.
      Needs that were unmet were mainly a result of lack of continuity. Caring for the
      terminally ill via primary nursing in a team setting was regarded as two-sided by
      the nurses. It was seen as stimulating and rewarding, as well as demanding and
      burdensome. Therefore, the need for support to the nurses involved was deeply
      stressed.

PMID- 8261389
TI  - Chemotherapy agents: Part II.

PMID- 8261390
TI  - Controlled release, biodegradable cytokine depots: a new approach in cancer
      vaccine design.
AB  - Experimental studies using murine tumor models have demonstrated that potent
      systemic immunity can be generated using tumor vaccines engineered by gene
      transfer to secrete certain cytokines. The underlying physiological principle
      behind these strategies involves the sustained release of high doses of cytokine
      at the site of the tumor. In some cases, this paracrine approach appears to
      enhance tumor antigen presentation and avoids systemic cytokine toxicity. The
      widespread clinical use of autologous cytokine gene transduced tumor vaccines may
      be limited by the technical difficulty and labor intensity of individualized gene
      transfer. We have therefore explored an alternate approach to generating
      sustained release of cytokines local to the tumor cells. High doses of
      granulocyte-macrophage colony-stimulating factor encapsulated in cell-sized
      gelatin-chondroitin sulfate microspheres were mixed with irradiated tumor cells
      prior to s.c. injection. This vaccination scheme resulted in systemic anti-tumor
      immune responses comparable to granulocyte-macrophage colony-stimulating factor
      gene transduced tumor vaccines.

PMID- 8261391
TI  - Hypoxic mammalian cell radiosensitization by nitric oxide.
AB  - The bioregulatory molecule, nitric oxide (NO), was evaluated as a hypoxic cell
      radiosensitizer. Authentic NO gas was nearly as effective as oxygen in
      radiosensitizing hypoxic Chinese hamster V79 lung cells as evaluated using
      clonogenic assays. When NO was delivered to hypoxic Chinese hamster V79 cells
      using the NO-releasing agent (C2H5)2N[N(O)-NO]- Na+, radiosensitization was also
      observed with a sensitizer enhancement ratio of 2.4 (1 mM (C2H5)2N[N(O)NO]-Na+).
      Aerobic radiosensitivity was not affected at this concentration. The hypoxic cell
      radiosensitization properties of (C2H5)2N[N(O)NO]-Na+, coupled with the
      vasodilatory effects of NO on tumor vasculature, suggest that such agents open a
      new avenue of research in radiation oncology.

PMID- 8261392
TI  - Genomic instability in colorectal cancer: relationship to clinicopathological
      variables and family history.
AB  - Recent reports have suggested that one or more genes may cause replication errors
      (RER) during colorectal tumorigenesis. Additional alleles are seen in the tumors
      when analyzing random microsatellite loci. We have studied seven dinucleotide
      repeat loci, located on seven different chromosomes, by use of polymerase chain
      reaction amplification and denaturing polyacrylamide gel electrophoresis. We
      found that 16.5% (40 of 243) colorectal cancers showed RER at one or several loci
      (RER+). This includes 31% (4 of 13) among cases with a strong positive family
      history according to previously published criteria and 17% (35 of 207) among
      cases with no history of familial cancer. Interestingly, no significant
      association was found between RER+ tumors and a general familial clustering of
      cancer. Microsatellite instability was significantly associated with DNA diploid
      status of the tumor (P < 0.001), with the location of the tumor in the proximal
      colon (P < 0.001), and with poorly differentiated tumor phenotype (P < 0.001).
      Patients with RER+ at > or = 2 loci tumors had an increased survival (P = 0.05).
      We further analyzed 84 breast cancers and 86 male germ cell cancers using the
      same seven markers. None of the tumors were RER+, indicating that this phenomenon
      may be specific to certain types of tumors.

PMID- 8261393
TI  - Microsatellite instability is associated with tumors that characterize the
      hereditary non-polyposis colorectal carcinoma syndrome.
AB  - Microsatellite instability implying multiple replication errors (RER+ phenotype)
      characterizes a proportion of colorectal carcinomas, particularly those from
      patients with the hereditary non-polyposis colorectal carcinoma syndrome. We
      studied the incidence of microsatellite instability in more than 500 sporadic
      tumors representing 6 different types of cancer. Apart from colorectal carcinoma
      [see the paper by Lothe et al. (Cancer Res., 53:5849-5852, 1993)] the RER+
      phenotype was found in 18% (6 of 33) of gastric carcinomas and 22% (4 of 18) of
      endometrial carcinomas. In contrast, no evidence of this abnormality was detected
      in cancers of the lung (N = 85), breast (N = 84), and testis (N = 86).
      Importantly, the first three cancers, as opposed to the latter three, are
      characteristic of the hereditary non-polyposis colorectal carcinoma syndrome.
      These findings suggest that the cancers belonging to the hereditary non-polyposis
      colorectal carcinoma tumor spectrum may have essential pathogenetic steps in
      common, including a tendency to multiple replication errors.

PMID- 8261394
TI  - Genetic predisposition to transplacentally induced renal cell carcinomas in the
      Eker rat.
AB  - N-Ethyl-N-nitrosourea-induced transplacental renal carcinogenesis in the rat
      results primarily in Wilms' tumors, apparently because primitive nephroblasts are
      the preferred target. Our question is whether N-ethyl-N-nitrosourea-induced
      mutations in the fetal kidney would increase the number of adult-type renal cell
      carcinomas in the Eker rat, which is heterozygous for a mutation that predisposes
      to renal cell carcinoma. Surprisingly, renal cell tumors but no Wilm's tumors
      began to appear from as early as 1 week after birth. Thus, the inheritance of a
      renal cell carcinoma mutation determines the specificity of tumor histology even
      with in utero carcinogenesis.

PMID- 8261395
TI  - Imaging of activated natural killer cells in mice by positron emission
      tomography: preferential uptake in tumors.
AB  - Optimal delivery of immunologically active cells to target tissue(s) is important
      for improving adoptive immunotherapy of neoplastic diseases. By using positron
      emission tomography, we have measured the systemic distribution and tumor
      localization of locally injected, activated natural killer (NK) cells or
      nonactivated lymphocytes in the FSaII fibrosarcoma grown s.c. in the tail of C3H
      mice. Murine NK cells were isolated and expanded in the presence of interleukin 2
      and collected at 5 to 7 days after culture. These cells were then washed and
      labeled with [11C]methyl iodide, a positron-emitting isotope. Ten million
      activated or nonactivated cells were injected into the lateral tail vein distal
      to the tumor over a period of 2 min, and the accumulation of counts in the tumor
      was monitored during the injection and at 30-60 min postinjection. There was no
      significant difference in the rate of accumulation of activated NK cells (685 +/-
      264 (SE); n = 5) versus nonactivated splenic lymphocytes (595 +/- 105; n = 5)
      during the injection period. Whole body scans of the mice done at 30 min to 1 h
      postinjection showed that the number of activated cells retained within the tumor
      ranged from 4 to 30% (15.3 +/- 4.9%; n = 5) of the injected dose. Activated NK
      cells which were not retained by the tumor accumulated in the lungs, liver, and
      spleen. In contrast, from 3 to 4% (3.4 +/- 0.2%; n = 5) of nonactivated
      lymphocytes remained within the tumor by 1 h. Nonactivated cells were distributed
      more homogeneously throughout the systemic circulation than the activated cells,
      although these cells also demonstrated increased retention in the lungs, liver,
      and spleen. The present study demonstrates that positron emission tomography may
      be used to quantify the number of effector cells which accumulate within tumors
      and to determine their biodistribution. The retention of labeled cells within the
      tumor may also be used as a means of imaging the tumor. Finally, the preferential
      accumulation of effector cells in the tumor vasculature following local injection
      has useful implications for adoptive immunotherapy.

PMID- 8261396
TI  - Analysis of p53 antibodies in patients with various cancers define B-cell
      epitopes of human p53: distribution on primary structure and exposure on protein
      surface.
AB  - p53 antibodies have been found in sera of patients with breast and lung
      carcinomas and in children with B-lymphomas. We report here the presence of p53
      antibodies in sera of patients with 11 different types of cancer. The frequency
      of seropositives for p53 varied among the different types of cancer, but a
      correlation with the frequency of p53 gene alteration was established. Using a
      powerful peptide enzyme-linked immunosorbent assay, we demonstrated that the
      immune response of patients with p53 antibodies was restricted to a small subset
      of peptides localized in the amino and carboxy termini of p53, whatever the type
      of cancer. Given the similarities of the patterns of immune responses in patients
      with p53 antibodies and animals hyperimmunized with human p53, we propose that
      the p53 humoral response is the result of a self-immunization process which is
      itself the consequence of p53 protein accumulation in tumor cells.

PMID- 8261397
TI  - An exon 5 deletion variant of the estrogen receptor frequently coexpressed with
      wild-type estrogen receptor in human breast cancer.
AB  - Recent evidence suggests that the expression of estrogen receptor (ER) variants
      in breast cancer may interfere with wild-type (wt) ER function and be related to
      tumor progression and resistance to hormone treatment. One of these variants, ER
      delta E5, lacking that part of the hormone-binding domain encoded by exon 5, has
      previously been identified in breast tumors with the unusual estrogen receptor
      negative (ER-) and progesterone receptor positive (PgR+) phenotype and found to
      possess constitutive and hormone-independent transcriptional activity. Using a
      ribonuclease protection assay, we analyzed 27 breast tumors and 4 breast cell
      lines for the presence of this variant. We found the ER delta E5 variant to be
      expressed, not only in all of three ER-/PgR+ tumors but also in 19 of 20 ER+/PgR+
      or ER+/PgR- tumors. Moreover, the variant was always coexpressed with and often
      in excess of wtER. ER delta E5 was also found in three breast cancer cell lines
      (MCF7, T47D, and ZR75-1), although to a lesser extent than wtER. A complete
      absence of both ER delta E5 and wtER was noted in four ER-/PgR- tumors and one
      normal breast cell line (HBL-100). Thus, our data suggest that the occurrence of
      ER delta E5 in breast cancer may represent a critical stage in tumor progression
      to autonomy.

PMID- 8261398
TI  - Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin
      resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding
      topoisomerase IIalpha and the retinoic acid receptor alpha locus.
AB  - Previous studies using cloned lines of Adriamycin-sensitive and -resistant P388
      murine leukemia cells have suggested that a reduction in DNA topoisomerase II
      alpha (topo II alpha) enzyme activity and protein levels in drug-resistant cell
      lines (A. M. Deffie, J. K. Batra, and G. J. Goldenberg, Cancer Res., 49: 58-62,
      1989) may be due to an allelic mutation in the topo II alpha gene (A. M. Deffie,
      D. J. Bosman, and G. J. Goldenberg, Cancer Res., 49: 6879-6882, 1989). The drug
      resistant cell lines P388/ADR/3 and P388/ADR/7 express a shortened topo II alpha
      mRNA transcript in addition to the native transcript present in the drug
      sensitive P388/4 cell line. Using complementary DNA probes derived from the
      coding sequence and 3' untranslated region of the native mouse topo II alpha
      transcript, we have determined that the shorter 4.5-kilobase topo II alpha
      transcript expressed in the drug-resistant cell lines contains only 3.5-kilobases
      of topo II sequence from the 5'-terminus onwards. Using a 3'-rapid amplification
      of cDNA ends strategy, we have cloned cDNAs representing the 3'-termini of both
      the native and mutant transcripts from both P388/ADR/3 and P388/ADR/7 cells. DNA
      sequence analysis revealed that the shorter 4.5-kilobase transcript: (a) encodes
      topoisomerase II alpha until nucleotide position 3494, at which point the
      sequence diverges for the remaining 956 bases; (b) contains a polyadenylation
      signal distinct from the native transcript; and (c) contains an open reading
      frame predicting a truncated topo II alpha fusion protein. Of great interest was
      the finding that the non-topo II alpha 956-base sequence in the shorter
      transcript encodes the promoter, exon I, and part of the first intron of the
      murine retinoic acid receptor alpha gene locus in the antisense orientation,
      suggesting that a rearrangement on chromosome 11 in the drug-resistant cells led
      to a gene fusion event between the loci encoding topo II alpha and retinoic acid
      receptor alpha.

PMID- 8261399
TI  - Prevention--therapy--basic science and the resolution of the cancer problem.

PMID- 8261400
TI  - Phospholipase activation triggers apoptosis in photosensitized mouse lymphoma
      cells.
AB  - Photodynamic therapy (PDT), an experimental cancer treatment employing a
      photosensitizer and visible light, is a highly efficient inducer of apoptosis (or
      programmed cell death) in mouse L5178Y lymphoma cells, resulting in extensive DNA
      fragmentation within 1-2 h. The major targets for PDT are in cellular membranes,
      and we now find that PDT sensitized by aluminum phthalocyanine causes the rapid
      (< 1 min) activation of phospholipase C and the breakdown of membrane
      phosphoinositides, as well as a similarly rapid release of Ca2+ from
      intracellular pools. A phospholipase C inhibitor, U73122, blocks the rapid
      transient increases in both inositol-1,4,5-trisphosphate and intracellular Ca2+
      levels as well as the subsequent fragmentation of nuclear DNA, whereas the
      analogue U73343 is much less effective against all of the aforementioned
      responses. In addition, p-bromphenacyl bromide, an inhibitor of phospholipase A2,
      blocks DNA fragmentation, and PDT stimulates the release of arachidonic acid,
      probably by phospholipase A2-dependent breakdown of membrane phospholipids. Thus,
      photodynamic damage to cell membranes can mimic natural stimuli of phospholipases
      and initiate apoptosis in L5178Y cells.

PMID- 8261401
TI  - Compensatory occurrence of IV2Fucalpha,II3NeuAcalpha-Gg4Cer and human fetal
      antigen Lc4Cer in small cell carcinomas of the human lung.
AB  - By means of a thin-layer chromatography immunostaining procedure involving a
      human monoclonal anti-Lc4Cer antibody, which was established by hybridizing
      murine myeloma cells and human lymphocytes from a cancer patient, Lc4Cer was
      proven to be a fetal antigen of human lung and to be a cancer-related antigen in
      small cell carcinomas of human lung, but not of other lung cancers, i.e., large
      cell carcinomas, adenocarcinomas, and squamous carcinomas. With the simultaneous
      detection of IV2Fuc alpha,II3NeuAc alpha-Gg4Cer with rabbit anti-IV2Fuc
      alpha,II3NeuAc alpha-Gg4Cer antiserum, the expression of Lc4Cer and IV2Fuc
      alpha,II3NeuAc alpha-Gg4Cer was found to be compensatory and, consequently, small
      cell lung carcinomas could be classified into Lc4Cer- and IV2Fuc alpha,II3NeuAc
      alpha-Gg4Cer-expressing types, L-SCLC and F-SCLC, respectively, which were
      detected in four and 27 of 31 patients' tissues and in one and three of four nude
      mouse-transplanted small cell lung carcinoma tissues, respectively. The
      compensatory expression of Lc4Cer and IV2Fuc alpha,II3NeuAc alpha-Gg4Cer in small
      cell carcinomas indicated that different metabolic pathways for
      glycosphingolipids were activated to give the distinct glycosphingolipid
      compositions in the two types of small cell lung carcinomas.

PMID- 8261402
TI  - Interaction between replication forks and topoisomerase I-DNA cleavable
      complexes: studies in a cell-free SV40 DNA replication system.
AB  - The extreme S-phase-specific cytotoxicity of camptothecin has been shown to
      involve active DNA replication. To investigate the role of DNA replication in
      camptothecin cytotoxicity, we have studied the interaction between the DNA
      replication machinery and the topoisomerase I-camptothecin-DNA ternary cleavable
      complex in a cell-free SV40 DNA replication system. The formation of
      topoisomerase I-camptothecin-DNA-cleavable complexes on the replication template
      efficiently and irreversibly inhibited DNA replication. Two aberrant forms of
      replication products were produced whose abundance varied with the concentrations
      of exogenously added topoisomerase I and camptothecin. At low concentrations of
      topoisomerase I and camptothecin, the major aberrant DNA replication product was
      close-to-unit-length-linear DNA, while at higher concentrations the predominant
      product was close-to-dimer-size-linear DNA. Analysis of these aberrant
      replication products has suggested a "collision" model in which the interaction
      between an advancing replication fork and a topoisomerase I-camptothecin-DNA
      cleavable complex results in irreversible arrest of the replication fork and the
      formation of a double-strand DNA break at the fork. Concomitant with fork arrest
      and fork breakage, the reversible cleavable complex was converted into a
      topoisomerase I-linked DNA break. We propose that one or several of these events
      triggers S-phase-specific cell killing and G2-phase cell cycle arrest.

PMID- 8261403
TI  - Pharmacokinetics of recombinant human interleukin 3 administered subcutaneously
      and by continuous intravenous infusion in patients after chemotherapy for ovarian
      cancer.
AB  - Twenty chemotherapy-naive patients with ovarian carcinoma received 1, 5, 10, or
      15 micrograms/kg/day (five patients per dose step) of recombinant human
      interleukin 3 (rhIL-3) over 7 days after carboplatin/cyclophosphamide in Cycles 1
      and 3. Patients received rhIL-3 by continuous i.v. infusion or once daily s.c.
      injection in Cycle 1 and the alternate route in Cycle 3. Plasma rhIL-3 samples
      were obtained once daily on Days 1 to 6 and serially over a 24-h period on Day 7
      for pharmacokinetic assessment of s.c. and i.v. administered rhIL-3 in 16 and 17
      patients, respectively. Concentrations were assayed by a time-resolved
      fluorescence sandwich immunoassay. Pharmacokinetic parameters were derived by
      noncompartmental methods. Mean steady-state concentrations during continuous i.v.
      infusion ranged from 117 pg/ml (1 microgram/kg/day) to 2217 pg/ml (15
      micrograms/kg/day) and were linearly related to dose (r = 0.87, P < 0.001). When
      dose normalized, the mean steady-state concentrations were comparable at all
      doses. The total-body clearance was approximately 4 to 5 ml/min/kg. Elimination
      half-life (t1/2 i.v.) could be assessed for the 5- to 15-micrograms/kg/day dose
      levels and was 53, 41, and 26 min for the 5-, 10-, and 15-micrograms dose levels,
      respectively (not significant between dose levels). Following s.c. injection, the
      maximum rhIL-3 plasma concentration ranged from 206 pg/ml (1 microgram/kg/day) to
      6930 pg/ml (15 micrograms/kg/day). Both the maximum measured plasma concentration
      (r = 0.89, P < 0.0001) and the area under the plasma concentration/time curve (r
      = 0.93, P < 0.0001) were related to dose. Dose-normalized values were comparable
      over the entire dose range. Elimination t1/2s.c. was 4.8 h at the 1-microgram
      dose level and roughly half this time for the 5- to 15-micrograms/kg/day dose
      levels. The systemic clearance of approximately 5 to 6 ml/min/kg was comparable
      at all dose levels. Based on trough levels of the 7-day s.c. course, no rhIL-3
      accumulation occurred. Bioavailability of s.c. administered rhIL-3 was nearly
      100%. No correlation between creatinine clearance and pharmacokinetic parameters
      of rhIL-3 could be demonstrated. Since there was also no difference in
      hematological efficacy between the two routes of rhIL-3 administration, we
      conclude that the s.c. route of administration appears to have no disadvantages
      over the i.v. route and may facilitate its clinical application.

PMID- 8261404
TI  - Tumor detection with 131I-labeled human monoclonal antibody COU-1 in patients
      with suspected colorectal carcinoma.
AB  - A major factor limiting the use of rodent monoclonal antibodies for diagnosis and
      therapy of cancer is the development of human anti-mouse immunoglobulin
      antibodies. Here we report a phase I/II immunodetection study of a human
      monoclonal antibody, COU-1, labeled with 131I. COU-1 is produced by a human-human
      hybridoma and recognizes a M(r) 43,000 cytokeratin-like protein strongly
      expressed by adenocarcinomas of the colon, breast, and ovary. Ten patients were
      given an i.v. infusion of 2 mg of antibody COU-1 labeled with 185 MBq of 131I. No
      adverse effects or toxicity were detected by conventional clinical tests nor by a
      complement activation assay for C3d. None of the patients developed antibodies
      against antibody COU-1 as determined by enzyme-linked immunosorbent assay and
      agglutination analysis. Tumor detection was successful in 7 of 9 cancer patients.
      The tenth patient proved to be a true negative. In several instances
      immunoscintigraphy gave additional or more correct information than conventional
      detection techniques. Tumors were most clearly outlined at days 5 and 7 after
      infusion. Primary colorectal carcinomas were detected by planar imaging in the
      cecum, ascending colon, and rectum with the smallest lesion measuring 3.0 cm in
      diameter. Immunoscintigraphy revealed multiple liver metastases in 1 of 3
      patients. However, the livers of all 3 patients contained significantly more
      radioactivity (P < 0.005) than tumor-free livers of the other patients.
      Pharmacokinetics was evaluated in all patients. The clearance of 131I-labeled COU
      1 from the circulation followed a triphasic pattern; an initial phase [t1/2 = 0.4
      +/- 0.4 (SD) h] cleared 23% of the radioactivity followed by a rapid phase with a
      half-life of 13 +/- 3.8 h. The third phase (beta-phase) exhibited a half-life of
      119 +/- 36 h, which is similar to the half-life reported for normal IgM. The
      human monoclonal antibody COU-1 directed against a predominantly intracellular
      cancer-associated antigen does not produce toxicity or induce antibody formation
      and seems to be a promising agent for detecting tumors with immunoscintigraphy.

PMID- 8261405
TI  - A randomized phase I trial of chronic oral etoposide with or without granulocyte
      macrophage colony-stimulating factor in patients with advanced malignancies.
AB  - Data from an in vitro human tumor-cloning assay suggested synergistic
      cytotoxicity when etoposide (VP16) and granulocyte-macrophage colony-stimulating
      factor (GM-CSF) were combined. To explore this potential, we undertook a
      prospectively randomized three-arm trial in a phase I setting with various
      schedules of VP16 and GM-CSF. Thirty-one patients were enrolled in the three-arm
      trial. Arm A consisted of oral VP16 daily for up to 21 days with cycles repeated
      every 35 days. Arm B included oral VP16 daily for up to 21 days plus concomitant
      GM-CSF at 5 micrograms/kg/day s.c. days 1-10. Arm C included oral VP16 daily for
      up to 21 days plus pretreatment with GM-CSF at the same dose for 5 days (days -6
      to -2). VP16 was begun at 25 mg/m2/day on level 1 and increased to 50 mg/m2/day
      on level 2. Twenty-seven patients were evaluable for toxicity, nine on each arm
      (six patients on each arm on level 1, three patients on each arm on level 2).
      Neutropenia on arm B (concomitant VP16 and GM-CSF) was earlier and more profound
      than on arm A or C. The median absolute neutrophil count and day of nadir for
      arms A, B, and C were 3295, 988, and 1600/mm3 and days 23, 15, and 26,
      respectively. Thrombocytopenia was generally uncommon except on arm C level 2,
      where the median platelet count was 26,000/mm3. One partial response (arm B) in a
      patient with non-small cell lung cancer was seen. Dose intensity favored arm A.
      Neither concomitant therapy with VP16 and GM-CSF (arm B) nor pretreatment with GM
      CSF (arm C) improved dose intensity over VP16 alone (arm A), and arms B and C
      were complicated by increased neutropenia and thrombocytopenia.

PMID- 8261406
TI  - Expression of a constitutively active estrogen receptor variant in the estrogen
      receptor-negative BT-20 human breast cancer cell line.
AB  - Estrogen receptor (ER) expression by breast tumors is an important predictor of
      disease-free survival in breast cancer patients and, more importantly, is a
      strong predictor of response to endocrine therapy. Variant forms of the ER may
      play an important role in the loss of hormone responsiveness and the progression
      to hormone independence. We have examined a panel of human breast tumor cell
      lines, both ER-positive and ER-negative, and have identified an ER mRNA variant
      containing a deletion of exon 5 in the ER-negative BT-20 and ER-positive MCF-7
      cell lines. This exon 5 deletion variant has been previously reported to be
      overexpressed in ER-negative/progesterone receptor-positive breast tumors. Using
      RNase protection analysis, we have found that the predominant ER transcript in
      the BT-20 cells is the exon 5 deletion variant, while the principal transcript in
      MCF-7 cells is the wild-type ER mRNA. The variant ER transcript is translated
      into a truncated receptor protein of approximately M(r) 42,000 when expressed in
      yeast and, more important, in breast tumor cells. This is the first demonstration
      of an exon 5 deletion variant ER protein. Functional analysis has shown that this
      variant ER possesses constitutive transcriptional regulatory activity with
      respect to an estrogen-regulated reporter gene construct in a yeast expression
      system. The presence of this ER variant in breast tumor cell lines, as well as
      breast tumor biopsies and uterine tissue, suggests that it is a naturally
      occurring variant that may arise by alternative splicing, and whose
      overexpression may be involved in the progression of breast tumors to a hormone
      independent state.

PMID- 8261407
TI  - Estradiol induction of retinoic acid receptors in human breast cancer cells.
AB  - Retinoic acid inhibits proliferation and steroid receptor gene expression in
      human breast cancer cell lines. Retinoic acid receptors (RAR)alpha, -beta, and 
      gamma are expressed in these cells and the expression of RAR alpha is
      significantly greater in estrogen receptor (ER)-positive cells. This study was
      undertaken to determine whether the same relationship between RAR alpha and ER
      gene expression was present in human breast cancers and to explore the
      possibility that the higher level of RAR alpha in ER-positive cells was due to
      estrogen regulation of RAR alpha gene expression. RAR alpha and ER mRNA
      expression were determined by Northern blot analysis in 116 primary breast
      tumors; 94 (81%) tumors were ER-positive and of these 87 (93%) were also RAR
      alpha-positive. The coexpression of ER and RAR alpha was statistically
      significant (P = 0.0052 by chi 2 contingency analysis). There was also a positive
      correlation (by linear regression analysis) between the levels of expression of
      ER and RAR alpha mRNA (r2 = 0.251, P = 0.0001), which confirmed the relationship
      previously documented in breast cancer cell lines and suggested that RAR alpha
      expression may be modulated in breast cancer in vivo by estrogens acting via the
      ER. The ability of estradiol to regulate RAR alpha gene expression was examined
      in vitro using T-47D cells which had been rendered sensitive to estrogen by
      repeated passage in steroid-depleted medium. Estradiol increased RAR alpha gene
      expression, but not that of RAR beta or RAR gamma, in a concentration-dependent
      manner, with the effect being maximal at 10(-10) M and less marked at higher
      concentrations. The effect was rapid, being detectable 1 h after and maximal 6 h
      after treatment with 10(-10) M estradiol. Co-treatment of cells with estradiol
      and antiestrogens (tamoxifen or ICI 164384, 4 x 10(-7) M for 6 h) inhibited the
      estradiol induction of RAR alpha gene expression, demonstrating that the effect
      was ER mediated. The estradiol sensitivity of the effect was underscored by the
      demonstration that addition of untreated serum to cells growing under steroid
      depleted conditions was sufficient to induce maximal RAR alpha gene expression.
      This effect was totally abolished by addition of ICI 164384. In summary, the
      demonstration that estradiol increased RAR alpha mRNA levels in breast cancer
      cells supports the hypothesis that the correlation between RAR alpha and ER gene
      expression in breast tumors and breast cancer cell lines is due to estradiol
      augmentation of RAR alpha gene expression.

PMID- 8261408
TI  - Teniposide-resistant CEM cells, which express mutant DNA topoisomerase II alpha,
      when treated with non-complex-stabilizing inhibitors of the enzyme, display no
      cross-resistance and reveal aberrant functions of the mutant enzyme.
AB  - We have examined the effects of a group of DNA topoisomerase II (topo II)
      inhibitors, merbarone, aclarubicin, SN22995, RP60475F, and fostriecin, in CCRF
      CEM cells and two sublines, CEM/VM-1 and CEM/VM-1-5, that were selected for
      increasing resistance to teniposide (VM-26). The teniposide-resistant sublines
      have been termed "at-MDR" for altered topo II-associated multidrug resistance.
      These topo II inhibitors differ from the "classic" inhibitors such as teniposide
      in that they do not stabilize DNA-topo II complexes. In this study, we found that
      our at-MDR cell lines express little or no cross-resistance to these "non
      classic" topo II inhibitors. Merbarone and SN22995 inhibited VM-26-mediated DNA
      topo II complexes in CEM cells only when they were added before VM-26. Since they
      did not deplete topo II protein, it suggested that these drugs may inhibit topo
      II activity before the enzyme binds to DNA, thereby preventing stabilization of
      VM-26-mediated topo II-DNA complexes. Continuous exposure of CEM cells to
      merbarone, SN22995, or VM-26 caused G2 arrest, as determined by flow cytometry.
      Likewise, at-MDR cells continuously treated with VM-26 also arrested in G2. By
      contrast, treatment of at-MDR cells with either merbarone or SN22995 produced a
      qualitatively different pattern; the at-MDR cells first accumulated in G2 but
      then escaped the G2 block and proceeded into mitosis with elongated and
      intertwined chromosomes but failed to divide. Their DNA was re-replicated,
      however, and the cells eventually accumulated at the 8N DNA stage. Given that
      both wild-type and mutant topo II alpha alleles are expressed in the at-MDR cells
      (B. Y. Bugg, M. K. Danks, W. T. Beck, and D. P. Suttle. Expression of a mutant
      DNA topoisomerase II in CCRF-CEM human leukemic cells selected for resistance to
      teniposide. Proc. Natl. Acad. Sci. USA, 88: 7654-7658, 1991), we hypothesize that
      drugs such as merbarone may inhibit the activity of wild-type topo II alpha,
      allowing the aberrant activity of the mutant enzyme to be revealed during
      chromosome condensation and sister chromatid segregation.

PMID- 8261409
TI  - Pharmacokinetics of a fluorescent drug using laser-induced fluorescence.
AB  - Laser-induced fluorescence has been used to measure tissue levels of
      chloroaluminum sulfonated phthalocyanine in vivo in an implanted hamster cheek
      pouch carcinoma tumor model. The drug was excited at 610 nm via a pulsed nitrogen
      laser-pumped dye laser, and fluorescence intensity was monitored at 684 nm for up
      to 30 days after drug administration. Data were acquired noninvasively with high
      temporal and spatial resolution using the laser-induced fluorescence apparatus
      and were analyzed with a multicompartment pharmacokinetic model. In addition, our
      published data on a C6-BAG glioma rat brain tumor model were analyzed to
      illustrate the effect of different tumor models on the rates. The rates extracted
      from the pharmacokinetic model elucidate the mechanisms of drug uptake and
      retention in the cheek pouch and brain tumor models. The laser-induced
      fluorescence approach should lead to better drug dosimetry for photochemotherapy
      and allow quick characterization of the pharmacokinetics of new photosensitizers
      in tissue.

PMID- 8261410
TI  - The protective role of ammonium trichloro(dioxoethylene-O,O')tellurate in
      combination with several cytotoxic drugs acting by different mechanisms of
      action.
AB  - We have demonstrated previously that the immunomodulator AS101 can protect mice
      from acute lethal toxicity mediated by high doses of radiation or chemotherapy.
      The compound was shown to rescue mice from toxic effects of cyclophosphamide or 5
      fluorouracil. The results presented herein demonstrate that pretreatment of mice
      with AS101 protects them from lethal effects of several chemotherapeutic drugs
      acting by distinct mechanisms. At sublethal doses, AS101 could prevent
      hemopoietic damage caused by the drugs. A significantly higher proportion of
      colony forming cells granulocyte-macrophage as well as a higher level of colony
      stimulating factor secretion by bone marrow (BM) cells was observed in mice
      pretreated with AS101 before injection of doxorubicin or
      cyclohexylchloroethylnitrosourea. Moreover, a significantly higher rate of
      survival was observed in mice injected with AS101 before treatment with lethal
      doses of these drugs. AS101 could also rescue BM stromal cells from damages
      caused by doxorubicin. We show that injection of mice with AS101 or pretreatment
      of BM cells with AS101 protects BM-colony forming cells granulocyte-macrophage
      from toxic effects of etoposide. We suggest that the protective effects of AS101
      against damages caused by a variety of cytotoxic drugs may be attributed to the
      ability of the compound to expand the colony forming unit spleen subpopulation of
      early progenitors, those cells that are resistant to several DNA damaging agents
      and are the precursor cells essential for reconstitution of the hemopoietic
      system. It seems that AS101, by minimizing adverse cytotoxicity resulting from a
      variety of drugs, is a promising candidate for chemoimmunotherapy with cancer
      patients.

PMID- 8261411
TI  - In vitro cytotoxicity, protein binding, red blood cell partitioning, and
      biotransformation of oxaliplatin.
AB  - The in vitro cytotoxicity, protein binding, partitioning of platinum from whole
      blood into erythrocytes, its exchange back into plasma, and the in vitro
      biotransformation in plasma were studied for the new nonnephrotoxic platinum
      analogue oxaliplatin. The cytotoxicity studies were carried out against a panel
      of human tumor cell lines derived from carcinomas of the ovary (A2780, A2780/cp),
      bladder (TCCSUP, RT4), colon (HT-29), melanoma (SKMEL-2, HTB144), and glioma
      (U373MG and U87MG). The relative potency of the five platinum complexes was
      oxaliplatin = tetraplatin > cisplatin > iproplatin > carboplatin. Oxaliplatin was
      active against HT-29 and only minimally cross-resistant with cisplatin against
      A2780/cp. Both bladder carcinoma cell lines, both melanoma cell lines, and one of
      the two glioblastoma cell lines were resistant to both oxaliplatin and
      tetraplatin. The cytotoxicity profiles of the drug pairs oxaliplatin-tetraplatin
      and cisplatin-carboplatin showed statistically significant correlation by the
      Spearman rank correlation test. Oxaliplatin was similar to cisplatin and
      tetraplatin in protein binding; 85-88% of all platinum from oxaliplatin (5, 10,
      or 20 micrograms/ml) was bound to plasma proteins within the first 5 h with an
      average half-life of 1.71 +/- 0.06 h. When oxaliplatin was incubated in whole
      blood (5, 10, and 20 micrograms/ml), the erythrocytes took up 37.1 +/- 2.1% of
      the total platinum in 2 h (maximum uptake) which was not exchangeable into
      plasma. Thus the erythrocyte-bound fraction does not serve as a reservoir of
      drug. In plasma, oxaliplatin was unchanged at 0.5 h, but at 1 h, 30% of the total
      platinum in plasma was in a peak which had identical retention to that of (trans
      1,2-diaminocyclohexane)dichloroplatinum(II), the major biotransformation product
      of tetraplatin. At 2 h, (trans-1,2-diaminocyclohexane)dichloroplatinum(II) and
      three other platinum-containing peaks were detected but no unchanged oxaliplatin.
      All the platinum eluted in a single peak near the solvent front at 4 h. The
      marked similarity in cytotoxicity between oxaliplatin and tetraplatin may be due
      to the formation of (trans-1,2-diaminocyclohexane)dichloroplatinum(II) in tissue
      culture media.

PMID- 8261412
TI  - Intoplicine (RP 60475) and its derivatives, a new class of antitumor agents
      inhibiting both topoisomerase I and II activities.
AB  - Intoplicine (RP 60475, NSC 645008) is an antitumor derivative in the 7H
      benzo[e]pyrido[4,3-b]indole series which is now being tested in clinical trials.
      Intoplicine strongly binds DNA (KA = 2 x 10(5) M-1) and thereby increases the
      length of linear DNA. These properties are consistent with DNA unwinding by
      intoplicine. Intoplicine was found to be a dual topoisomerase I and II inhibitor,
      with DNA sites of enzyme inhibition being different for these two enzymes. In
      this study, 22 analogues of intoplicine were evaluated for their effects on
      topoisomerase I- and II-mediated DNA cleavage reactions by using enzymes purified
      from calf thymus. Site-specific DNA cleavage mediated by topoisomerase I was
      observed with 7H-benzo[e]pyrido[4,3-b]indole derivatives but not with 11H
      benzo[g]-pyrido[4,3-b]indole derivatives. Site-specific DNA cleavage mediated by
      topoisomerase II occurred with derivatives having hydroxyl groups at the 3
      position on the 7H-benzo[e]pyrido[4,3-b]indole ring or at the 4-position on the
      11H-benzo[g]pyrido[4,3-b]indole ring. Study of the relationships between the in
      vivo antitumor activity on P388 leukemia and the topoisomerase I- and/or II
      mediated DNA cleavage activity revealed that the most highly active antitumor
      compounds possessed both topoisomerase I-and II-inhibitory properties. Compounds
      selectively inhibiting either topoisomerase I or II were less active. These
      results suggest that dual topoisomerase I and II inhibition is critical for the
      antitumor activity of this new series of antitumor compounds.

PMID- 8261413
TI  - Suppression of stress protein GRP78 induction in tumor B/C10ME eliminates
      resistance to cell mediated cytotoxicity.
AB  - Tumor cells undergo self-destruction when incubated with cytotoxic T-cells (CTL)
      consistent with the observation that suppression of target protein synthesis
      causes resistance to apoptosis. Resistance to CTL is also induced by stress,
      suggesting that pathways exist suppressing apoptosis. Here we examine whether
      stress induced lysis resistance to CTL and tumor necrosis factor alpha involves
      stress proteins GRP78 and GRP94. We show that inhibition of GRP78 synthesis by
      transfection of cells with grp78 antisense vector pRSV-78WO leads to inability to
      induce resistance to CTL or tumor necrosis factor alpha. Resistance induced in
      untransfected cells is reversible upon stress removal and correlates with GRP78
      rephosphorylation, consistent with the notion that phosphorylated GRP78 is
      nonfunctional. The possibility that GRP78 plays a role in defense against CTL
      mediated apoptosis is supported by the finding that CTL but not CD4+ cells
      express a high level of unphosphorylated GRP78.

PMID- 8261414
TI  - 1 alpha,25-dihydroxyvitamin D3 plus gamma-interferon blocks lung tumor production
      of granulocyte-macrophage colony-stimulating factor and induction of
      immunosuppressor cells.
AB  - Metastatic Lewis lung carcinoma (LLC-LN7) cells have previously been shown to
      produce granulocyte-macrophage colony-stimulating factor (GM-CSF) which induces
      the appearance of immunosuppressive granulocytic-macrophage progenitor cells (GM
      suppressor cells). The present in vitro studies showed that treatment of LLC-LN7
      tumor cells with 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] plus low dose gamma
      interferon (IFN-gamma) resulted in a synergistic reduction in tumor GM-CSF
      secretion and a blockage in the capacity of the tumor cells to induce GM
      suppressor cells. The production of GM-CSF by bulk cultures of enzymatically
      dissociated LLC-LN7 tumors that had been excised as s.c. tumors from mice was
      also blocked when the dissociated tumor was cultured with 1,25(OH)2D3 plus IFN
      gamma. Our previous and present studies showed that GM-suppressor cells persist
      in bulk cultures of dissociated LLC-LN7 tumors after a 1-week period of culture.
      Addition of either 1,25(OH)2D3 or IFN-gamma did not diminish the persistence of
      GM-suppressor cells. However, when tumor production of GM-CSF was inhibited by
      culture with both 1,25(OH)2D3 and IFN-gamma, the ability of the dissociated tumor
      culture to sustain the presence of GM-suppressor cells was blocked. This
      elimination of GM-suppressor cells by treatment of the dissociated tumor with
      1,25(OH)2D3 and IFN-gamma coincided with increased expansion of CD8+ tumor
      infiltrating leukocytes and increased cytotoxic T-lymphocytes activity of tumor
      infiltrating lymphocytes. These results suggest that blocking tumor production of
      GM-CSF can interrupt the suppressor-inducing cascade of the tumor and enhance
      expansion and anti-tumor cytolytic reactivity of tumor-infiltrating leukocytes.

PMID- 8261415
TI  - Complementation of the radiosensitive phenotype in severe combined
      immunodeficient mice by human chromosome 8.
AB  - Severe combined immunodeficient (scid) C.B-17 mice are deficient in variable
      (diversity) joining region recombination, the process of assembling the
      immunoglobulin and T-cell receptor genes from gene segments, thereby creating
      much of the enormous diversity of antigen-binding capacity, scid mice are also
      sensitive to ionizing radiation, as a result of their deficiency in double-strand
      break repair. Here we report the complementation of the radiation-sensitive scid
      phenotype by transferring human chromosome 8 into scid cells. Somatic cell
      hybrids were generated by fusing scid cells with human HT-1080 cells, resulting
      in radioresistant hybrids with several human chromosomes. One of the identified
      human chromosomes in the radioresistant scid cell line 4.61, which retains only
      two human chromosomes, is a rearranged 8/21 translocation. Proof that chromosome
      8 confers the complementation was achieved by transferring only human chromosome
      8 into scid cells by microcell-mediated chromosome transfer (scid/hu8 cell line).
      The presence of chromosome 8 in our scid/hu8 cell line was monitored by
      fluorescence in situ hybridization and polymerase chain reaction. We demonstrated
      the radioresistance of this hybrid not only to high dose rate but also to low
      dose rate radiation. We also showed that transference of human chromosome 8 to
      scid cells fully complements the DNA double-strand break repair deficiency and
      the high sensitivity of scid cells to radiation-induced chromosome aberrations.
      Mapping the scid gene to human chromosome 8 is an important first step in cloning
      the scid gene, which will enhance our understanding of double-strand break repair
      pathways in humans.

PMID- 8261416
TI  - Annexin II expression is regulated during mammalian cell cycle.
AB  - Annexin II is a substrate for oncogene and growth factor-associated protein
      tyrosine kinases. Elevated expression of annexin II is seen in different types of
      cancers and recent evidence indicates a role for annexin II in DNA synthesis and
      cell proliferation. In this report we show that the level of annexin II is
      subject to cell cycle regulation. Chinese hamster ovary cells were selected
      without the use of drugs, by the mitotic cell selection technique. As the mitotic
      cells progressed synchronously through the cell cycle, we determined the steady
      state levels of annexin II mRNA and protein. The half-life of annexin II mRNA was
      approximately 2 h as measured by pulse-chase and ribonuclease protection
      analyses. Steady-state levels of both annexin II mRNA and protein were high in
      mitotic cells. As the cells divided and entered G1, there was a reduction in the
      levels of both annexin II mRNA and protein. New synthesis of annexin II mRNA and
      protein occurred in early G1 and maximal expression of annexin II mRNA and
      protein occurred as the cells entered S-phase. A gradual reduction in steady
      state levels of annexin II mRNA and protein occurred as cells progressed through
      S-phase. Similar results were obtained in HeLa cells. In HeLa cells, collected at
      various cell cycle stages by countercurrent centrifugal elutriation, we observed
      peak expression of annexin II in G1-S and S-G2 cells. We conclude from our
      results that annexin II expression is regulated during the mammalian cell cycle.

PMID- 8261417
TI  - Infrequency of MDM2 gene amplification in pediatric solid tumors and lack of
      association with p53 mutations in adult squamous cell carcinomas.
AB  - Loss of function of the p53 tumor suppressor gene by point mutation is the most
      commonly detected genetic alteration in human cancer. There is growing evidence
      that amplification and overexpression of the MDM2 gene are alternative mechanisms
      that also lead to functional inactivation of p53. While p53 mutations and MDM2
      amplification have been reported to occur in rhabdomyosarcoma and osteogenic
      sarcoma, the incidence of MDM2 in other pediatric solid tumors is not known. We
      therefore tested a series of other pediatric solid tumors for MDM2 gene
      amplification. MDM2 amplification could not be detected in specimens from 40
      Wilms' tumors, 15 neuroblastomas, 12 sarcomas, or 4 hepatoblastomas tested. To
      determine whether MDM2 amplification was an alternative mechanism of p53
      inactivation in adult carcinomas that frequently possess p53 mutations, 68
      samples of squamous cell carcinomas of the upper aerodigestive tract, 24% of
      which were previously shown to contain p53 mutations, were also tested for MDM2
      amplification. MDM2 amplification did not occur in any of the tumor specimens
      tested. These findings suggest that MDM2 amplification may only occur in a
      limited subset of human tumors. Loss of function of p53 may be an essential event
      in human tumorigenesis. If so, then other mechanisms of p53 inactivation must
      occur in those tumors that exhibit neither p53 mutation nor MDM2 amplification.

PMID- 8261418
TI  - Allelic variation in the dihydrofolate reductase gene at amino acid position 95
      contributes to antifolate resistance in Chinese hamster cells.
AB  - The Chinese hamster lung cell line DC-3F contains two polymorphic dihydrofolate
      reductase (DHFR) alleles that are defined by an Asp-Asn amino acid sequence
      difference at position 95 in protein. Previously, we reported that the antifolate
      resistant subline DC-3F/A3 overexpressed a Leu22-->Phe mutant of the Asp95 (21k)
      allele and that this was the basis of its resistance to methotrexate (MTX) and
      methasquin [P. W. Melera, J. P. Davide, C. A. Hession, and K. W. Scotto, Mol.
      Cell. Biol., 4: 38-48, 1984]. We now show that another independently selected
      antifolate-resistant subline of DC-3F, DC-3F8/A55, in addition to being severely
      compromised in its ability to accumulate MTX, overexpresses a Leu22-->Phe mutant
      form of the Asn95 (20k) allele. Characterization of purified DHFR from these
      cells showed that the enzyme displayed a 6-fold higher Kd for MTX (3.92 +/- 0.17
      pM) than the wild type (0.58 +/- 0.10 pM), thus explaining its lowered
      sensitivity to drug. Unexpectedly, however, this value was 4-fold lower than that
      displayed by the DC-3F/A3 enzyme even though both contain the same (Leu22-->Phe)
      mutation and differ only at position 95. Indeed, we have also shown that the 21k
      and 20k wild type enzymes, both containing Leu at position 22, in fact differ by
      3-fold (1.58 +/- 0.08 and 0.58 +/- 0.10 pM, respectively) in their Kd's for MTX.
      This demonstrates that the amino acid at position 95 has an effect on the ability
      of DHFR to bind MTX. On the other hand, these allelic variants are
      indistinguishable from each other in their catalytic properties and in their
      respective Kd's for dihydrofolate. Taken together, these characteristics are
      consistent with the observation that it is the wild type 21k allele which is
      preferentially overexpressed at a frequency of 3:1 in MTX-resistant Chinese
      hamster lung sublines derived by long-term selection in MTX. The results of these
      studies are novel in that they establish a role for allelic variation in the DHFR
      gene as a contributor to antifolate resistance in mammalian cells. Moreover, they
      implicate amino acid position 95 in the maintenance of the structure of the MTX
      binding pocket.

PMID- 8261420
TI  - Statistical analysis of in vivo tumor growth experiments.
AB  - We review and compare statistical methods for the analysis of in vivo tumor
      growth experiments. The methods most commonly used are deficient in that they
      have either low power or misleading type I error rates. We propose a set of
      multivariate statistical modeling methods that correct these problems,
      illustrating their application with data from a study of the effect of alpha
      difluoromethylornithine on growth of the BT-20 human breast tumor in nude mice.
      All the methods find significant differences between the alpha
      difluoromethylornithine dose groups, but recommended sample sizes for a
      subsequent study are much smaller with the multivariate methods. We conclude that
      the multivariate methods are preferable and present guidelines for their use.

PMID- 8261419
TI  - N-(4-hydroxyphenyl)retinamide induces apoptosis of malignant hemopoietic cell
      lines including those unresponsive to retinoic acid.
AB  - N-(4-Hydroxyphenyl)retinamide (HPR) is a synthetic retinoid of particular
      clinical interest in cancer chemoprevention. We have examined the in vitro
      effects of HPR on lymphoid and myeloid malignant cell lines and found that at
      concentrations between 10(-5) and 3 x 10(-7) M it induces a dose-dependent growth
      inhibition (the peak plasma concentration in patients treated with HPR is 1 to 2
      x 10(-6) M). The antiproliferative effect of HPR was, in all cell lines except
      K422, more potent than that induced by an equimolar dose of all-trans retinoic
      acid (RA). Also, this effect was irreversible on HL60 and DoHH2 cells that had
      been exposed to HPR (3 x 10(-6) M) for 24 h, but reversible on Raji and DHL4
      exposed to the retinoid for 48 and 72 h, respectively. Time-course growth
      analysis showed that HPR at 3 x 10(-6) M or below induces a rapid fall of
      thymidine uptake and viability (> 90%), whereas between 10(-6) and 3 x 10(-7) M
      exhibits cytostatic effects. Interestingly, the RA-resistant HL-60R and NB306
      cells, characterized by a point mutation in the retinoic acid receptor (RAR) and
      by the loss of the pml/RAR protein, respectively, were, like the parental RA
      inducible HL-60 and NB4 cell lines, fully responsive to HPR, thereby suggesting
      that HPR and RA could act through different receptors or pathways. DNA flow
      cytofluorimetric analysis revealed that HPR does not block cells in a specific
      phase of the cell cycle but triggers programmed cell death or apoptosis. This
      phenomenon was evidenced both by the visualization, on gel electrophoresis, of
      fragmented DNA, and by the "in cell" enzymatic labeling of DNA breaks with
      fluorescent dUTP. With the latter method, apoptotic cells become detectable by 6
      h following exposure to 3 x 10(-6) M HPR. Ultrastructural examination of HPR
      treated samples showed cells with chromatin compaction and cytoplasm
      condensation, characteristic of apoptotic cells. In conclusion, our study
      demonstrates that HPR suppresses malignant cell growth and induces apoptosis at
      pharmacologically relevant doses. The differential responsiveness by a number of
      cell lines, especially HL-60R and NB306, to HPR and RA indicates that these
      compounds may act through different receptors. The clinical use of HPR,
      particularly in retinoic acid-unresponsive acute promyelocytic leukemia patients,
      is suggested.

PMID- 8261421
TI  - Inhibition of invasion of HT1080 sarcoma cells expressing recombinant plasminogen
      activator inhibitor 2.
AB  - Plasminogen activators (PA) elaborated by tumor cells play an important role in
      the complex process of tissue invasion and metastasis. In the present study the
      effect of the PA inhibitor type 2 (PAI-2) on tissue invasion in vitro and in vivo
      was investigated. Clones either expressing (B-) or not expressing the endogenous
      PAI-2 gene (C+) were isolated from the human HT1080 fibrosarcoma cell line and
      transfected with full-length PAI-2 cDNA. Recombinant PAI-2 (rPAI-2) expressed by
      these cells completely inhibited receptor-bound urokinase activity and partially
      neutralized secreted PA activity. Degradation of extracellular matrix proteins by
      these transfected cells was markedly decreased when compared to mock or
      untransfected control cells. The rPAI-2-expressing cells did not penetrate a
      multilayer of rat smooth muscle cells in vitro, which was readily invaded and
      destroyed by control cells. The PAI-2 transfectants remained tumorigenic in
      athymic/nude mice, but tumors originating from these cells showed the presence of
      a thick, collagenous capsule absent in tumors formed by control cells. Thus,
      expression of rPAI-2 in HT1080 cells resulted in neutralization of receptor-bound
      urokinase with subsequent inhibition of matrix protein degradation and invasion
      in vitro and induction of a thick, peritumoral capsule in vivo.

PMID- 8261422
TI  - Z-4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (MDL 28,842), an irreversible
      inhibitor of S-adenosylhomocysteine hydrolase, suppresses proliferation of
      cultured keratinocytes and squamous carcinoma cell lines.
AB  - S-Adenosylmethionine-dependent transmethylation reactions are required for many
      critical pathways in human cells. The enzyme S-adenosylhomocysteine hydrolase
      converts S-adenosylhomocysteine, a potent endogenous inhibitor of S
      adenosylmethione-mediated methyltransferase reactions, to adenosine and L
      homocysteine. The effects of the inhibitor of S-adenosylhomocysteine hydrolase, Z
      4',5'-didehydro-5'-deoxy-5'-fluoroadenosine (MDL 28,842), on the growth of
      cultured keratinocytes and cutaneous squamous cell carcinoma lines were
      investigated. MDL 28,842 suppressed the proliferation of all cells in a dose
      dependent manner, and significantly increased keratinocyte differentiation at a
      concentration of 1 microM. Following incubation with MDL 28,842, the methylation
      indices (ratio of S-adenosylmethionine/S-adenosylhomocysteine) of
      undifferentiated keratinocytes and squamous cell carcinoma lines were
      significantly decreased. These data demonstrate that the inhibitory effect of MDL
      28,842 on squamous carcinoma cells and keratinocyte proliferation may result
      directly from inhibition of S-adenosylhomocysteine hydrolase activity. The
      antiproliferative activity of MDL 28,842 against squamous carcinoma cells and
      keratinocytes suggests a potential role for MDL 28,842 as a novel therapeutic
      agent for neoplastic and hyperproliferative disorders of the skin.

PMID- 8261423
TI  - Expression of calcyclin in human melanocytic lesions.
AB  - When comparing two subsequent stages of melanocytic tumor progression we
      identified calcyclin as a new potential progression marker, the expression of
      which was correlated with metastatic behavior of various human melanoma cell
      lines in nude mice. In this study, we describe a good correlation between RNA and
      protein levels in the xenografts of these cell lines and extended these
      experiments to a panel of 120 routinely processed human melanocytic cutaneous
      lesions. Northern blot analysis demonstrated that calcyclin RNA expression was
      elevated in melanoma metastases as compared to several types of nevocellular
      nevi. Calcyclin staining using a specific polyclonal antiserum showed a more
      complex pattern. A stronger staining in a higher percentage of positive cells was
      observed in thick primary melanoma (> or = 1.5 mm) as compared to thin primary
      melanoma (< 1.5 mm). Calcyclin expression was also present in a higher percentage
      of cells showing a stronger staining in melanomas with higher Clark levels (> II)
      corresponding to the vertical growth phase of primary melanomas. Protein
      expression in nevocellular nevi was confined to the dermal part and was highest
      in the lower parts of the dermis. Remarkably, dysplastic nevi (atypical moles),
      potential precursors of melanoma, did not show any expression at all, either in
      junctional or dermal parts. Confinement of the expression to the dermal part of
      nondysplastic nevi and primary melanomas may reflect interactions with the
      microenvironment of the reticular dermis that occurs with vertical growth.

PMID- 8261424
TI  - Sequence analysis of an immunogenic and neutralizing domain of the human T-cell
      lymphoma/leukemia virus type I gp46 surface membrane protein among various
      primate T-cell lymphoma/leukemia virus isolates including those from a patient
      with both HTLV-I-associated myelopathy and adult T-cell leukemia.
AB  - Human T-cell lymphoma/leukemia virus type I (HTLV-I) causes adult T-cell
      leukemia/lymphoma and HTLV-I-associated myelopathy. Specific regions within the
      outer envelope proteins of other retroviruses, e.g., human immunodeficiency virus
      type 1, are highly immunogenic and, because of the selective pressure of the host
      immune system, quite variable. Mutations in the external envelope protein gene of
      murine retroviruses and human immunodeficiency virus type 1 influence cellular
      tropism and disease pathogenesis. By contrast, no disease-specific viral
      mutations have been identified in HTLV-I-infected patients. However, all isolates
      studied thus far have originated from leukemic cell lines, peripheral blood
      mononuclear cells, or cerebrospinal fluid lymphocytes from patients with HTLV-I
      associated myelopathy and adult T-cell leukemia/lymphoma and, therefore, may not
      truly reflect tissue-associated variation. The midregion of the HTLV-I gp46
      external envelope glycoprotein (amino acids 190-209) induces an antibody response
      in 90% of infected individuals, and a hexapeptide in this region (amino acids 191
      196) elicits antibodies in rabbits which inhibit syncytia formation and infection
      of target lymphocytes. Because of the above, we expected the neutralizing domain
      of the gp46 env gene of HTLV-I to possess disease or organ-associated mutations
      selected by the infected host's immune system. Hence, we amplified, cloned, and
      sequenced HTLV-I DNA directly from in vivo central nervous system, spleen, and
      kidney specimens, and a leukemic cell line from a patient (M. J.) with both HTLV
      I-associated myelopathy and adult T-cell leukemia/lymphoma to discern the
      possibility of tissue- and/or disease-specific variants. In addition, we
      sequenced several HTLV-I isolates from different regions of the world, including
      Papua New Guinea, Bellona, and Liberia, and compared them to other previously
      published HTLV-I and related retroviral sequences. The 239-base pair sequence
      corresponding to amino acids 178 to 256 in gp46 displayed minor tissue-specific
      variation in clones derived from central nervous system tissues from patient M.
      J., but overall was highly conserved at both the DNA and amino acid levels.
      Variation was observed in this region among the other HTLV-I, simian T-cell
      lymphoma virus type I, and HTLV-II isolates in a pattern that was consistent with
      their known phylogenetic relationship. No consistent disease-related changes were
      observed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8261425
TI  - Aspirin use and risk of fatal cancer. Cancer Res., 53: 1322-1327, 1993.

PMID- 8261426
TI  - Intra- and interindividual variability in systemic exposure in humans to 2-amino
      3,8-dimethylimidazo[4,5-f]-quinoxaline and 2-amino-1-methyl-6-phenylimidazo-[4,5
      b]pyridine, carcinogens present in cooked beef. Cancer Res., 52: 6216-6223, 1992.

PMID- 8261427
TI  - Heterogeneity of subcellular localization of p53 protein in human glioblastomas.
AB  - Immunohistochemical analysis of the p53 protein in human glioblastomas with known
      genetic profiles of p53 mutations and allele losses on chromosome 17p
      demonstrated a heterogeneous pattern of subcellular compartmentalization of the
      p53 protein. Tumors with a single wild type copy of the p53 gene but with allelic
      deletions on chromosome 17p exhibit nuclear and/or cytoplasmic accumulation of
      p53, whereas tumors with both copies of the wild type gene and no allele losses
      on chromosome 17 do not accumulate p53. Glioblastomas with one normal and one
      mutated copy of the p53 gene and allelic deletions on 17p distal to p53, on the
      other hand, show predominantly cytoplasmic staining, probably originating from
      the wild type p53 protein. Furthermore, tumors with mutations in the same codon
      of p53 display quite different intracellular distribution suggesting that, in
      addition to the genotype of p53, the intracellular microenvironment of a
      particular tumor is important in determining the subcellular localization of the
      p53 protein.

PMID- 8261429
TI  - Clinical pharmacology of 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate,
      an orally administered long-acting derivative of low-dose 1-beta-D
      arabinofuranosylcytosine.
AB  - 1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (cytarabine ocfosfate,
      stearyl-ara-CMP) is a newly synthesized 5'-alkylphosphate derivative of 1-beta-D
      arabinofuranosylcytosine (ara-C), which is lipophilic, resistant to inactivation
      by deamination, and orally active. Pharmacology of this drug was studied in
      patients with hematological malignancies. The concentrations of stearyl-ara-CMP,
      ara-C (its active metabolite), and 1-beta-D-arabinofuranosyluracil (ara-U, its
      inactive metabolite) were determined by radioimmunoassay. When six patients
      received a single p.o. dose of the drug (500 mg/m2), stearyl-ara-CMP, ara-C, and
      ara-U could be detected in the plasma for at least 72 h afterwards. The plasma
      disappearance curve of stearyl-ara-CMP corresponded to a one-compartment open
      model with first-order absorption kinetics. The peak plasma level (Cmax) was 322
      +/- 218 nM, and the predicted time to reach Cmax (Tmax) was 6.5 +/- 4.5 h, while
      the elimination half-life (t1/2) was very long (32.0 +/- 8.4 h). The plasma ara-C
      level increased slowly to a Cmax of 26.3 +/- 12.7 nM (Tmax, 13.3 +/- 4.7 h) after
      stearyl-ara-CMP administration. This level was quite low compared with that
      achieved by low-dose s.c. ara-C therapy, but ara-C persisted longer in the plasma
      in the former case, and the area under the curve was similar for both regimens.
      For ara-U, the Cmax, Tmax, and t1/2 were 483 +/- 315 nM, 23.6 +/- 4.0 h, and 19.6
      +/- 5.3 h, respectively. No stearyl-ara-CMP was detected in the urine, and only
      8.0% of the administered dose was excreted as ara-C and ara-U within 72 h. The
      stearyl-ara-CMP concentration in the cerebrospinal fluid was below the limit of
      detection in three patients without meningeal involvement at 6 h. During clinical
      use of stearyl-ara-CMP, macrocytic anemia was observed, and some patients also
      developed megaloblastic change of their erythroblasts, suggesting a mild and
      persistent cytostatic effect. In conclusion, p.o. therapy with stearyl-ara-CMP
      achieved prolonged maintenance of the plasma drug level. Thus, the drug released
      a very low dose of ara-C over a long period in plasma and tissues and had a
      prolonged mild antineoplastic effect in patients with hematological malignancies.

PMID- 8261428
TI  - Role of human microsomal and human complementary DNA-expressed cytochromes
      P4501A2 and P4503A4 in the bioactivation of aflatoxin B1.
AB  - The metabolism of the carcinogenic mycotoxin aflatoxin B1 (AFB1) was examined in
      microsomes derived from human lymphoblastoid cell lines expressing transfected
      CYP1A2 or CYP3A4 complementary DNAs and in microsomes prepared from human liver
      donors (n = 4). Lymphoblast microsomes expressing only CYP1A2 activated AFB1 to
      AFB1-8,9-epoxide (AFB1-8,9-epoxide trapped as the glutathione, conjugate) at both
      16 microM and 128 microM AFB1 concentrations, whereas activation of AFB1 to the
      epoxide in lymphoblast microsomes expressing only CYP3A4 was detected only at
      high substrate concentrations (128 microM AFB1). AFB1 epoxidation was strongly
      inhibited in CYP1A2 but not CYP3A4 lymphoblast microsomes pretreated with
      furafylline, a specific mechanism-based CYP1A2 inhibitor, whereas troleandomycin
      (TAO), a specific CYP3A inhibitor, strongly inhibited AFB1 epoxidation in CYP3A4
      but not CYP1A2 microsomes. Formation of the hydroxylated metabolite aflatoxin M1
      (AFM1) was observed only in the CYP1A2 microsomes whereas aflatoxin Q1 (AFQ1)
      production was observed exclusively in the CYP3A4 microsomes. Treatment of
      individual human liver microsomes (HLM) with TAO resulted in an average 20%
      inhibition of AFB1-8,9-epoxide formation at 16 microM AFB1, whereas incubation of
      HLM with furafylline at 16 microM AFB1 resulted in an average 72% inhibition of
      AFB1-8,9-epoxide formation at 16 microM AFB1. TAO was slightly more effective
      than furafylline in inhibiting AFB1 epoxidation at 128 microM AFB1 (46%
      inhibition by TAO, 32% inhibition by furafylline) in HLM. AFB1-8,9-epoxide
      formation was inhibited by 89% at low substrate concentration and 85% at high
      substrate concentrations when HLM were inhibited with a furafylline/TAO mixture.
      AFM1 formation was strongly inhibited by furafylline, whereas AFQ1 formation was
      strongly inhibited by TAO, in all HLM regardless of substrate concentration.
      Analysis of R-6- and R-10-hydroxywarfarin activities (respective markers of
      CYP1A2 and CYP3A4 activities) in the complementary DNA-expressed microsomes
      demonstrated that TAO was less effective than furafylline as a selective P450
      isoenzyme inhibitor (60% inhibition of CYP3A4 by TAO as compared to 99%
      inhibition of CYP1A2 by furafylline). The rates of AFB1 epoxidation and AFQ1
      formation in HLM were increased 7- and 18-fold, respectively, at high versus low
      substrate concentrations. These results are consistent with the hypothesis that
      CYP1A2 is the high-affinity P450 enzyme principally responsible for the
      bioactivation of AFB1 at low substrate concentrations associated with dietary
      exposure. CYP3A4 appears to have a relatively low affinity for AFB1 epoxidation
      and is primarily involved in AFB1 detoxification through AFQ1 formation in
      HLM.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8261430
TI  - Phase I and pharmacokinetic study of a new antineoplastic agent: pyrazine
      diazohydroxide (NSC 361456).
AB  - Pyrazine diazohydroxide (PZDH) is a novel antineoplastic agent that appears to
      form DNA adducts via the reactive pyrazine diazonium ion and produces substantial
      antitumor activity in preclinical models. We conducted a phase I trial to
      determine the maximally tolerated dose of PZDH that could be administered as a 5
      min i.v. bolus for 5 consecutive days repeated every 28 days. Thirty-one patients
      with advanced cancer refractory to standard therapy received a total of 65 cycles
      of therapy at 7 sequential PZDH dose levels: 18, 36, 45, 56, 75, 100, and 133
      mg/m2/day. At the maximally tolerated dose (133 mg/m2/day x 5), all 4 patients
      experienced grade 3-4 thrombocytopenia, and 3 of 4 had grade 3-4 neutropenia. At
      the recommended phase II dose (100 mg/m2/day x 5), the median WBC nadir following
      the first cycle was 2.5 x 10(3)/microliters (range, 0.6-7.6) occurring on day 36,
      and the median platelet nadir was 87 x 10(3)/microliters (range, 9-155) occurring
      on day 26. Nausea and vomiting occurred at all dose levels, but were well
      controlled with ondansetron. No evidence of hepatic, renal, pulmonary, cardiac,
      venous, dermatological, or neurological toxicity was observed. Pharmacokinetic
      evaluations were performed on 28 of the 31 patients using an analytical method
      including derivatization of the parent drug to 2-chloropyrazine. We report the
      total 2-chloropyrazine, which represents PZDH converted per method plus PZDH
      converted in vivo. Although the assay quantitation limit is 10 ng/ml, PZDH could
      only be detected at the first dose level for 30-90 min after the i.v. bolus.
      Compartmental modeling of the first 4 dose levels was most consistent with a 2
      compartment model. Subsequent dose levels revealed a third phase to the plasma
      decay curve. The area under the plasma drug concentration-time curve increased
      proportionally with dose; there was no evidence for dose-dependent
      pharmacokinetics. Pharmacokinetic parameters for 12 patients analyzed by the 3
      compartment model revealed an alpha-half-life (t1/2 alpha) of 2.83 +/- 1.57 (mean
      +/- SD), a t1/2 beta of 11.9 +/- 4.42, and a t1/2 gamma of 161 +/- 47.1 min, with
      a mean clearance of 1.86 +/- 0.91 liters/min. At the 100- and 133-mg/m2 dose
      levels, the mean areas under the plasma drug concentration-time curve were 105
      and 169 micrograms min/ml, respectively. There was a moderate correlation between
      body surface area and clearance (r = 0.45, P = 0.015) but a better correlation
      between weight and clearance (r = 0.53, P = 0.004).(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8261431
TI  - X-irradiation, phorbol esters, and H2O2 stimulate mitogen-activated protein
      kinase activity in NIH-3T3 cells through the formation of reactive oxygen
      intermediates.
AB  - Extracellular signal-regulated kinases (ERKs), also known as mitogen-activated
      protein (MAP) kinases, are rapidly phosphorylated and activated in response to a
      number of external factors which promote growth and differentiation (T. G.
      Boulton, S. H. Nye, D. J. Robbins, N. Y. Ip, E. Radziejewska, S. D. Morgenbesser,
      R. A. DePinho, N. Panayotatos, M. H. Cobb, and G. D. Yancopoulos, Cell, 65: 663
      675, 1991; S. L. Pelech and S. S. Jasbinder, Science (Washington DC), 257: 1355
      1356, 1992; G. Thomas, Cell, 68: 3-6, 1992). We have identified two novel
      stimulators of MAP kinase activity, ionizing radiation and H2O2. Both radiation
      and H2O2, as well as the known agonist 12-O-tetradecanoylphorbol 13-acetate
      activate MAP kinase through the production of reactive oxygen intermediates. Our
      results demonstrate a direct link between the MAP kinase signal transduction
      pathway and reactive oxygen species and provide a unifying mechanism for
      activation of early- and late-response genes by inducers of oxidative stress.

PMID- 8261432
TI  - Urokinase and plasminogen activator inhibitor type 1 in pulmonary adenocarcinoma.
AB  - The urokinase pathway of plasminogen activation is involved in proteolytic
      degradation of various tissues, including dissolution of the extracellular matrix
      and basement membranes during the process of cancer cell invasion. We have
      studied the prognostic value of urokinase-type plasminogen activator (uPA) and
      type-1 plasminogen activator inhibitor (PAI-1) in tumor extracts from 106
      patients with adenocarcinoma of the lung. uPA and PAI-1 levels were determined by
      sandwich enzyme-linked immunosorbent assays. No correlation was found between uPA
      and PAI-1 (r = 0.23). High PAI-1 levels were significantly associated with short
      duration overall survival (P = 0.017), while uPA levels showed no significant
      association with overall survival. Relating the levels of PAI-1 to other
      prognostic factors such as stage and age, no significant correlations were found.
      The prognostic impact of uPA and PAI-1 were investigated together with other
      prognostic factors in Cox multivariate analysis. PAI-1 was found to be an
      independent prognostic variable for survival, the relative risks being 1.5 (low
      versus medium PAI-1 values (95% confidence interval, 1.2-1.8) and 2.2 (low versus
      high (95% confidence interval, 1.8-2.6)). In patients with stage I disease (69
      patients) high levels of PAI-1 were significantly associated with poor prognosis
      compared to low levels (P = 0.037). These data indicate that PAI-1 is a
      potentially important prognostic factor in pulmonary adenocarcinoma and may as
      such be used to select patients with low stage and poor prognosis for adjuvant
      therapy subsequent to complete surgical resection.

PMID- 8261433
TI  - Identification, characterization, and biological activity of somatostatin
      receptors in human neuroblastoma cell lines.
AB  - To investigate the presence of biologically active somatostatin (SS) receptors in
      neural crest-derived tumors, radioligand binding studies, cyclic AMP
      accumulation, intracellular calcium, and growth assays were performed in eight
      human neuroblastoma (NB) cell lines. Mathematical modeling of binding experiments
      strongly indicates the presence of heterogeneity of sites. The first site (SSR1)
      is present in 40% of the NB cell lines and binds with low capacity (0.5 pmol/mg
      protein) and high affinity (0.1-1 nM) SS14, SS28, and analogues. The second site
      (SSR2) is a high capacity site (200 pmol/mg protein), widely distributed in all
      of the cell lines investigated, that shows relative selectivity yet low affinity
      (100 nM) for SS14, SS28, and [D-Trp8]SS14 without any apparent biological
      activity. SSR1 is coupled to a pertussis toxin-sensitive G protein, inhibits
      forskolin- or VIP-stimulated adenylate cyclase activity, decreases intracellular
      free calcium, and mediates inhibition (30%) of both DNA synthesis and cell
      growth. Analysis of cell cycle distribution in aphidicolin-synchronized SSR1
      positive NB cells indicated that this inhibitory effect is partially mediated by
      a transient accumulation in G0-G1. Our data indicate high affinity binding sites
      for SS14, and analogues are present and biologically active in a subset of NB
      cells.

PMID- 8261434
TI  - A population-based seroepidemiological study of cervical cancer.
AB  - The epidemiology of cervical cancer indicates the presence of a sexually
      transmitted risk factor, attributable at least in part to infection with human
      papillomavirus (HPV) type 16 or 18. We performed a seroepidemiological study of
      HPV and cervical cancer in the counties of Vasterbotten and Norrbotten in
      Northern Sweden, a low-risk area for cervical cancer. Sera from 94 cases of
      incident cervical cancer were matched against 188 age- and sex-matched controls
      derived from a population-based blood bank. IgG and IgA antibodies were measured
      against a panel of 12 antigens derived from HPV types 6, 11, 16, or 18, as well
      as against Herpes simplex virus type 1 and 2, Chlamydia trachomatis,
      cytomegalovirus, Epstein-Barr virus, and bovine papillomavirus. Significantly
      increased relative risks (RRs) were found for IgG to HPV 16- or 18-derived
      antigens from the L1 (RR = 3.1), E2 (RRs = 2.8 and 9.2), and E7 (RRs = 3.8 and
      2.7) open reading frames and for IgA to HPV 16-derived antigens from the E2 (RR =
      3.3) and E6 (RR = 2.7) open reading frames. The highest RR (9.2, confidence
      intervals 4.4-19.4) was associated with IgG to an HPV 18 E2 antigen. Antibodies
      against cytomegalovirus, Herpes simplex virus type 2, Epstein-Barr virus, or
      bovine papillomavirus were, on their own, not significantly associated with
      cervical cancer, but seropositivity against multiple infections was associated
      with a successively increased relative risk. An increased risk was also found for
      IgG to Chlamydia trachomatis (RR = 1.7, confidence interval = 1.0-2.7). The
      results indicate that several HPV antibodies are strongly associated with
      cervical cancer, providing further seroepidemiological support for an etiological
      role of HPV in cervical cancer.

PMID- 8261435
TI  - Comparison of equitoxic radioimmunotherapy and chemotherapy in the treatment of
      human colonic cancer xenografts.
AB  - The therapeutic efficacy of 5-fluorouracil (5-FUra; 0.6 mg/day x 5 days) +
      leucovorin (LV; 1.8 mg/day x 5 days) and of 131I-labeled MN-14
      anticarcinoembryonic antigen IgG (275 microCi single dose) was evaluated in size
      matched (0.3-0.7 cm3) s.c. LoVo, HT-29, DLD-1, HCT-15, LS174T, and MOSER, GW-39,
      and WidR human colonic tumors. These lines express varying amounts of
      carcinoembryonic antigen and exhibit varying degrees of in vitro responsiveness
      to 5-FUra. Unlike radioimmunotherapy (RAIT), multiple cycles of chemotherapy were
      feasible over a 3-week period. However, no therapeutic advantage to a second
      cycle of 5-FUra/LV administration was found. Therefore, it is reasonable to
      compare single cycles of both treatment modalities. RAIT was statistically more
      effective in 5 of 8 tumor lines (LoVo, LS174T, MOSER, WidR, and GW-39). In 1
      other line (DLD-1), RAIT was marginally more efficacious, but tumors responded
      well to both therapies. The lack of a statistical difference between the 2
      modalities of treatment may indicate that the efficacy of the 2 treatments is
      equivalent, or the relatively large variability within the treatment groups may
      have prevented significance given the number of animals evaluated. RAIT and 5
      FUra/LV were equally efficacious in the HT-29 and the HCT-15 tumor lines. Of the
      5 xenografts that responded better to RAIT, 3 lines (LS174T, GW-39, and WidR)
      demonstrated a greater percentage of tumors responding over a 5- to 6-week
      period. The other 3 lines (LoVo, MOSER, and DLD-1) exhibited a similar percent of
      tumors responding to both therapies, but a greater growth inhibition in those
      RAIT-treated tumors that responded. In vitro responsiveness to 5-FUra/LV did not
      directly correlate with in vivo responsiveness (r2 = -0.664), since LS174T and
      LoVo tumors, with rapid growth rates (0.05-0.36 cm3/day), were not highly
      responsive to therapy. Growth inhibition from RAIT also did not correlate with
      total tumor carcinoembryonic antigen content (r2 = 0.003), an observation that
      may be due to additional variables, such as accessibility of antigen and innate
      radiosensitivity of the tumor. RAIT was most effective in the fastest growing
      tumor lines (LS174T, GW-39, MOSER, WidR, and LoVo). These preclinical results
      suggest an advantage to radioantibody therapy over one of the most commonly used
      forms of chemotherapy to treat colorectal cancer. These studies also highlight
      the need to establish criteria that will enable the selection of therapeutic
      modalities in patients.

PMID- 8261436
TI  - Efficacy of DMP 840: a novel bis-naphthalimide cytotoxic agent with human solid
      tumor xenograft selectivity.
AB  - DMP 840, a novel bis-naphthalimide, was evaluated for antitumor efficacy in
      several tumor models in mice. As measured by a tumor growth inhibition assay,
      i.v. administration of DMP 840 to athymic nude mice at doses at or below the
      maximum tolerated dose resulted in curative activity against four human solid
      tumor xenografts, MX-1 mammary carcinoma, CX-1 and DLD-2 colon adenocarcinomas,
      and LX-1 lung carcinoma, producing full or incomplete regressions and/or percent
      tumor growth inhibition of > or = 96%. The efficacy of DMP 840 in the models was
      dose dependent. The activity of DMP 840 against the human tumors surpassed that
      demonstrated by several clinically used and investigational anticancer agents. In
      long-term growth delay studies, DMP 840 induced full regressions in 20 of 20 mice
      bearing MX-1 tumors, and tumors in one-half of these mice remained regressed for
      over 5 months. In addition, DMP 840 was curative against exponentially growing
      DLD-2 tumors staged at 500 mg and MX-1 tumors staged at 1000 mg. The bis
      naphthalimide was equally efficacious when administered i.v. or i.p. but was
      slightly less active after oral dosing. Against both the MX-1 mammary carcinoma
      and the DLD-2 colon adenocarcinoma, some measure of schedule dependence was
      observed; the optimum schedule was daily for 9 days. Against L1210 and P388
      murine leukemias, DMP 840 demonstrated little or no activity and was inactive
      against B16 murine melanoma. Overall, these results suggest that DMP 840 may be a
      human solid tumor selective cytotoxic agent.

PMID- 8261437
TI  - Successful treatment of human Waldenstrom's macroglobulinemia with combination
      biological and chemotherapy agents.
AB  - The immunomodulating effects and antitumor activity of two biological agents,
      bryostatin 1 (Bryo1) and alpha-interferon, were tested in vitro and in vivo
      either alone or prior to chemotherapy agents, against a Waldenstrom's
      macroglobulinemia tumor line (WSU-WM). Bryol caused a decrease in the expression
      of CD10, CD19, IgM, Leu10, and CD22 and a temporary growth inhibition as measured
      by cell cycle analysis. alpha-Interferon did not show any major effects. In vivo,
      severe combined immunodeficient mice were used to test the activity of the agents
      against WSU-WM. Bryo1 (i.p.) was given either alone or sequentially with
      doxorubicin (i.v.), vincristine (i.v.), melphalan (i.v.), and alpha-interferon
      (i.v.). Bryo1 given 24 h before vincristine or melphalan resulted in the highest
      tumor growth inhibition, tumor growth delay, and tumor cell kill. Two of five
      mice receiving Bryo1/vincristine combination were free of tumors > 200 days after
      treatment and were considered cured. In light of our findings, we recommend that
      Bryo1 be considered for clinical investigation in human B-cell tumors and might
      best be given combined with other chemotherapy agents used in the treatment of
      that disease. Whether Bryo1 is acting as a differentiating agent or as a direct
      anti-Waldenstrom's macroglobulinemia tumor agent, remains unclear.

PMID- 8261438
TI  - Immunomodulation in patients with epithelial ovarian cancer after adoptive
      transfer of tumor-infiltrating lymphocytes.
AB  - The immunomodulation determined by natural killer cell activity, delayed-type
      hypersensitivity to purified protein derivative and phytohemagglutin, and
      phenotypic changes of peripheral blood lymphocytes was characterized in 12
      patients with epithelial ovarian cancer who received adoptive transfer of tumor
      infiltrating lymphocytes (TILs) after cisplatin-containing chemotherapy (TIL
      group). As a control, 10 patients with epithelial ovarian cancer who did not
      receive infusions of TIL were also examined in the same fashion. In the TIL
      group, peripheral blood lymphocytes showed increased percentages of cells bearing
      the CD8 antigen, in contrast to stable percentages of CD4 antigen-bearing cells,
      resulting in a decreased ratio of CD4+ to CD8+ cells. The percentages of CD16 and
      CD56 antigen-bearing cells also increased in proportion to augmentation of
      natural killer cell activity against K562 cells. Additionally, with regard to
      cell-mediated immunity determined by delayed-type hypersensitivity to
      phytohemagglutin and purified protein derivative, significantly and slightly
      enlarged erythema was observed 2 and 8 weeks, respectively, after the injection
      of TILs (phytohemagglutin, P < 0.05; purified protein derivative, not
      statistically significant). The control group showed no major changes in any of
      the immunological markers. These results suggest the possibility that the
      adoptive transfer of TILs induces immunoactivation of cellular immunity and
      enhances natural killer activity in patients with epithelial ovarian cancer.

PMID- 8261439
TI  - GD3 vaccines for melanoma: superior immunogenicity of keyhole limpet hemocyanin
      conjugate vaccines.
AB  - Cell surface gangliosides show altered patterns of expression as a consequence of
      malignant transformation and have therefore been of interest as potential targets
      for immunotherapy, including vaccine construction. One obstacle has been that
      some of the gangliosides that are overexpressed in human cancers are poorly
      immunogenic in humans. A case in point is GD3, a prominent ganglioside of human
      malignant melanoma. Using an approach that has been effective in the construction
      of bacterial carbohydrate vaccines, we have succeeded in increasing the
      immunogenicity of GD3 in the mouse by conjugating the ganglioside with
      immunogenic carriers. Several conjugation methods were used. The optimal
      procedure involved ozone cleavage of the double bond of GD3 in the ceramide
      backbone, introducing an aldehyde group, and coupling to aminolysyl groups of
      proteins by reductive amination. Conjugates were constructed with a synthetic
      multiple antigenic peptide expressing repeats of a malarial T-cell epitope, outer
      membrane proteins of Neisseria meningitidis, cationized bovine serum albumin,
      keyhole limpet hemocyanin, and polylysine. Mice immunized with these conjugates
      showed a stronger antibody response to GD3 than mice immunized with unconjugated
      GD3. The strongest response was observed in mice immunized with the keyhole
      limpet hemocyanin conjugate of the GD3 aldehyde derivative and the adjuvant QS
      21. These mice showed not only a long-lasting high-titer IgM response but also a
      consistent high-titer IgG response (predominantly IgG1), indicating recruitment
      of T-cell help, although the titers of IgM and IgG antibodies following booster
      immunizations were not as high as they are in the response to classical T-cell
      dependent antigens. This method is applicable to other gangliosides, and it may
      be useful in the construction of immunogenic ganglioside vaccines for the
      immunotherapy of human cancers expressing gangliosides on their cell surface.

PMID- 8261440
TI  - Potent mammary carcinogenicity in female CD rats of a fjord region diol-epoxide
      of benzo[c]phenanthrene compared to a bay region diol-epoxide of benzo[a]pyrene.
AB  - Two diol-epoxide metabolites of benzo[c]phenanthrene and benzo[a]pyrene,
      polynuclear aromatic hydrocarbons which occur in the environment, were tested for
      carcinogenicity by direct injection into the mammary fat pads of female CD rats.
      The compounds anti-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene
      (BcPDE), a fjord region diol-epoxide, and anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene, a bay region diol-epoxide, were applied at total doses
      of 12.2 mumol. 6-Nitrochrysene was applied at the same dose as a positive control
      (K. El-Bayoumy, A. Rivenson, P. Upadhyaya, Y-H. Chae, and S. S. Hecht, Cancer
      Res. 53: 3719-3722, 1993). The sterically hindered fjord region diol-epoxide
      BcPDE was a powerful mammary tumorigen and carcinogen, rapidly inducing
      significantly more fibroadenoma and adenocarcinoma than either of the other
      compounds. Anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene was a
      weaker mammary tumorigen than BcPDE and 6-nitrochrysene. The results of this
      study provide the first evidence for mammary tumorigenicity of polynuclear
      aromatic hydrocarbon diol-epoxides and demonstrate the potent mammary
      carcinogenicity of BcPDE.

PMID- 8261441
TI  - Low incidence of point mutations detected in the p53 tumor suppressor gene from
      chemically induced rat renal mesenchymal tumors.
AB  - Previous studies have shown renal mesenchymal tumors (RMTs) induced in rats by a
      single intrarenal injection of nickel subsulfide and iron are more pleomorphic
      and metastatically aggressive than RMTs induced by a single ip injection of
      methyl(methoxymethyl)nitrosamine (DMN-OMe). While both RMT types contain high
      levels of K-ras activation, the specific mutational spectra within codon 12 of K
      ras are quite different. Nickel subsulfide and iron-induced tumors exhibited
      codon 12 GGT-->GTT transversions exclusively, while DMN-OMe RMTs showed a wide
      array of codon 12 mutations, as well as mutations within codons 61 and 63 [K. G.
      Higinbotham, J. M. Rice, B. A. Diwan, K. S. Kasprzak, C. D. Reed, and A. O.
      Perantoni, Cancer Res., 52: 4747-4751, 1992; K. G. Higinbotham, J. M. Rice, and
      A. O. Perantoni, Mol. Carcinog., 5: 136-139, 1992]. In an effort to further
      correlate carcinogen-specific molecular events in renal tumors, we investigated
      the p53 tumor suppressor gene in RMTs induced by these two carcinogens for the
      presence of point mutations. The evolutionarily conserved portion of the coding
      region of the gene, including part of exon 4 through exon 10, was surveyed for
      point mutations utilizing single-strand conformation polymorphism and chemical
      cleavage of mismatches analyses. None (0 of 10) of the nickel subsulfide and iron
      induced RMTs and only 1 of 10 DMN-OMe-induced tumors that were evaluated
      contained point mutations within this portion of the p53 gene. Direct sequencing
      of the one single-strand conformation polymorphism and chemical cleavage of
      mismatches-"positive" DMN-OMe-induced RMT revealed a GCC-->GTC (Ala-->Val)
      transition in codon 345 within exon 10. These results suggest that the different
      tumorigenic phenotypes exhibited by these two RMTs are not the result of specific
      mutations or patterns of mutations within the portion of the p53 gene examined
      and that the mutated p53 tumorigenic pathway, whereby p53 plays a major role in
      many human neoplasms, does not function in RMTs induced by either agent.

PMID- 8261442
TI  - Developmentally regulated expression of two novel platelet-derived growth factor
      alpha-receptor transcripts in human teratocarcinoma cells.
AB  - Two novel platelet-derived growth factor (PDGF) alpha-receptor transcripts of 1.5
      kilobases and 5.0 kilobases are expressed in the human teratocarcinoma cell line
      Tera-2 only while the cells are in an undifferentiated state. After retinoic acid
      induced differentiation, expression of these mRNAs is completely shut off and
      instead, the cells express a single 6.4-kilobase mRNA species which is also
      expressed in many other cell types. The 1.5-kilobase mRNA initiates within intron
      12, contains the correctly spliced exons 13, 14, 15, and 16, and contains a
      cryptic exon, designated teratocarcinoma cryptic exon, at the 3' end.
      Teratocarcinoma cryptic exon contains a functional polyadenylation signal. Exons
      13 to 16 correspond to the first tyrosine kinase domain and to part of the
      interkinase domain of the PDGF alpha-receptor. Recently, a splice variant lacking
      exon 14 was identified. These results show that a combination of alternative
      promoter usage and alternative splicing of the human PDGF alpha-receptor gene
      occur in a developmentally regulated fashion. In vitro translation of the 1.5
      kilobase mRNA generates protein products which can be specifically
      immunoprecipitated with a PDGF alpha-receptor-specific antibody. The significance
      of the expression of this transcript for the growth factor-independent
      proliferation of undifferentiated Tera-2 cells is unclear. Expression of PDGF
      alpha-receptor transcripts containing the cryptic exon may be useful as a marker
      for undifferentiated stem cells in human teratocarcinomas.

PMID- 8261443
TI  - Joining of recombination signals on the der 14q- chromosome in T-cell acute
      leukemia with t(10;14) chromosome translocation.
AB  - Sequence analysis of the translocation breakpoint junctions on the der(14q-)
      chromosome in six patients carrying a t(10;14) chromosome translocation revealed
      that the breakpoint occurred 5' to the HOX11 protooncogene at the breakpoint
      cluster region. HOX11 coding sequence was not effected. The translocation
      resulted in the joining of the V-(D)-J recombination signals 5' to the T-cell
      receptor D delta 2 segment on chromosome 14 with chromosome 10 at a location
      within a heptamer-like sequence. At the breakpoint junctions, the insertion of
      extra nucleotides, N-nucleotides, including P-nucleotides, was evident. The
      mechanism involved in this process is discussed.

PMID- 8261444
TI  - p53 gene abnormalities are closely related to hepatoviral infections and occur at
      a late stage of hepatocarcinogenesis.
AB  - Hepatocellular carcinoma (HCC) accumulates a mutation of the p53 gene with a
      common substitution of nucleotide in a particular site. It is hypothesized that
      infection of hepatitis B virus (HBV) or exposure to aflatoxins could induce it.
      In Japan, the concentration of aflatoxins in the environment is low; however,
      infection of HBV and/or hepatitis C virus (HCV) is frequently seen in patients
      with HCC. The purpose of our studies was to determine whether these hepatoviral
      factors influence p53 alterations. In our results, p53 abnormalities, which were
      composed of loss of heterozygosity (LOH) and/or point mutation, were shown in 39%
      of patients. We postulated that they occurred at late stages in tumor growth
      based on the following two results. LOH analysis on p53 showed that most of the
      tumor nodule consisted of two phenotypes, LOH and non-LOH cancer cells. The p53
      abnormalities correlated with the grade of cancer cell atypia which advanced with
      tumor growth. HBV and HCV infections were identified by polymerase chain reaction
      using DNA extracted from cancerous and noncancerous regions of the liver. By
      these methods, the patients who had been infected with either HBV or HCV showed
      an incidence of p53 abnormalities (45%) higher than those infected by neither
      (13%). However, the detection rate of these viruses was lower in the HCC region
      (33%) than that in the noncancerous region (56%) in cases with mutated p53. The
      low rate of HCV detection (22%) in the HCC region with altered p53 was
      attributable to these different viral detection rates. There was a difference in
      pattern of p53 mutational changes in patients depending upon whether they were
      infected by HBV or by HCV. Two of three HBV-infected patients had a
      transversional change of nucleotide at the G:C site to T:A. However, in cases
      with HCV, four of eight patients had a transitional change of nucleotide of p53.
      These results showed that HBV and HCV infections affect carcinogenic pathways
      causing p53 abnormalities independently.

PMID- 8261445
TI  - Telomere shortening in renal cell carcinoma.
AB  - The ends of human chromosomes consist of a specialized structure, the telomere,
      composed of repeats of TTAGGG making up a total of 5-15 kilobase pairs, depending
      on age and proliferative activity of the tissue. The major function of telomeres
      is to provide stability to chromosomes and protect underlying unique coding
      sequences from degradation. There is a loss of telomeric sequences following
      every cell division estimated to be between 50 and 65 basepairs/cell division in
      human fibroblasts and embryonic kidney cells in vitro. This loss is due to the
      fact that DNA replication is incomplete for one strand at each telomere end. In
      lower eukaryotes there is a compensation mechanism provided by the enzyme
      telomerase, which is inactive in human somatic cells. Telomerase activation has
      also been detected in vitro immortalized human cells. In this study we analyzed
      renal cell carcinoma for the occurrence of telomere shortening using the probe
      (TTAGGG)4. Southern blots of HinfI-digested DNA revealed a shortening of mean
      telomere restriction fragment (TRF) length of 0.4 to 2.5 kilobase pairs in 2 or 3
      intratumoral samples in all 10 tumors analyzed. No obvious intratumoral
      heterogeneity was found in mean TRF length values. However, heterogeneity was
      shown by the occurrence of at least two separate peak TRF values in 7 of 10
      tumors, indicating the presence of different tumor cell clones. A conflicting
      observation was made when we evaluated the intensity of the hybridization
      signals, where three of the tumors showed an increase in hybridization signals
      despite concomitant TRF reduction. We found no correlation between tumor size and
      calculated tumor cell divisions undergone. In two tumors, the calculated cell
      division cycles were unrealistically low compared to the tumor size. These data
      suggest that telomerase activation might occur in human renal cell carcinoma.

PMID- 8261446
TI  - Retinoblastoma protein expression is frequently altered in chronic lymphocytic
      leukemia.
AB  - The detection of abnormalities at the retinoblastoma (RB) locus by cytogenetics,
      Southern blot, and fluorescence in situ hybridization studies suggests that the
      RB gene has a role in chronic lymphocytic leukemia (CLL). To further study this
      role, we determined the level of RB protein present in the mononuclear cell
      fraction derived from peripheral blood or bone marrow samples from 74 patients
      with CLL, by Western blotting. Compared to similarly prepared samples from the
      peripheral blood of normal individuals, the level of RB in CLL cells was less
      than normal in 42% of patients, equal to normal in 22% of patients, and in excess
      of normal in 36% of patients. Regardless of whether the source of the sample was
      blood or marrow or if the patients were untreated or previously treated, similar
      rates of low, normal, and elevated RB levels were observed. RB protein in the CLL
      patient samples was never phosphorylated. RB levels showed no correlation with
      the lymphocyte doubling time or with proliferating cell nuclear antigen levels.
      Low RB levels could arise from genetic alterations of the RB gene or altered
      regulation of expression. To determine which was occurring, we stimulated the
      cells from 27 CLL patients in culture with either phytohemagglutinin or pokeweed
      mitogen in an attempt to induce RB expression and phosphorylation. Among patients
      with low levels of RB, expression was induced in 46% (6 of 13), and
      phosphorylation of RB was seen in 31% (4 of 13). Increased expression of
      phosphorylated RB was induced in 80% (4 of 5) of patients with normal levels of
      RB and in 78% (7 of 9) of patients with high levels of RB. This study
      demonstrates that absent RB expression occurs commonly in patients with CLL.
      Intrinsic abnormalities of the RB gene may be present in those patients with low
      levels of RB that could not be stimulated by mitogens, while regulatory
      abnormalities located in trans to the RB gene may occur in the other half. Given
      the importance that RB levels play in other cancers, the prognostic implication
      of low RB levels should be studied in CLL.

PMID- 8261447
TI  - Rat dihydrodiol dehydrogenase: complexity of gene structure and tissue-specific
      and sexually dimorphic gene expression.
AB  - Dihydrodiol dehydrogenase (DD; EC 1.3.1.20) catalyzes a novel pathway of
      polycyclic aromatic hydrocarbon (PAH) metabolism in which trans-dihydrodiols
      (proximate carcinogens) are oxidized to reactive o-quinones which are cytotoxic
      and genotoxic. In this study, the complementary DNA for rat liver DD was used to
      examine the structure and regulation of the DD gene. Southern analysis of rat
      genomic DNA confirmed that DD is a member of the multigene aldo-keto reductase
      superfamily. Conservative estimates indicate that the rat DD gene is at least 20
      25 kilobases in length. Northern analysis showed that the rat liver transcript
      was 2.4 kilobases whereas the complementary DNA contains an open-reading frame of
      966 nucleotides. Primer extension of male and female polyadenylated RNA indicated
      that the major transcription start sites are only 53 and 54 base pairs upstream
      from the translation start site, confirming that the RNA has a very long 3'
      untranslated region. In male and female tissues, 2.4 kilobase transcripts
      predominate in liver, small intestine, and lung, which is consistent with a role
      for the enzyme in PAH metabolism. Transcripts were also detected in male
      (prostate)- and female (ovary, mammary gland, and uterus)-specific tissues. In
      the ovary, two transcripts were observed of 2.4 and 1.4 kilobases in length.
      Using benzenedihydrodiol as a model substrate for PAH trans-dihydrodiols, highest
      levels of DD activity were observed in the liver and small intestine of both
      sexes. Enzyme activity is 2.5-fold higher in the female liver versus the male
      liver. This sexual dimorphism can be explained by increases in the DD mRNA and
      enzyme protein as measured by dot-blot and immunotitration analyses,
      respectively. The latter measurements indicate that DD represents 1.0% of the
      soluble protein in female liver but is only 0.5% of the soluble protein in male
      liver. Hormonal ablation (ovariectomy and hypophysectomy) abolishes the sexual
      dimorphism observed in levels of DD mRNA, enzyme protein, and enzyme activity.
      Administration of estrogens to males is sufficient to establish the female
      pattern of gene expression. These data indicate that DD gene expression is
      hormonally regulated, that estrogens exert their effect at the level of the mRNA,
      and that aldo-keto reductases involved in PAH metabolism may have their
      expression regulated by female sex hormones.

PMID- 8261448
TI  - Progression of basal cell carcinoma through loss of chromosome 9q and
      inactivation of a single p53 allele.
AB  - Basal cell carcinoma (BCC) of the skin represents a unique group of tumors
      strongly associated with exposure to UV light. Unlike squamous carcinoma of the
      skin, BCC is generally indolent, noninvasive, and rarely metastatic. To study the
      involvement of tumor suppressor genes in these neoplasms, we analyzed 36 BCCs for
      p53 mutations and a subset of these tumors for loss of chromosomes 17p and 9q.
      Sixty-nine % of sporadic BCCs had lost a 9q allele, with the common area of loss
      surrounding the putative gene for nevoid BCC or Gorlin's syndrome. Forty-four %
      (16 of 36) of BCCs had a mutated p53 allele, usually opposite pyrimidine tracts,
      which is consistent with UV-induced mutations. Surprisingly, only one tumor had
      lost a 17p allele, and in all BCCs only one p53 allele was inactivated. This is
      in direct contrast to other epithelial tumors, which usually progress by the
      inactivation of both p53 alleles.

PMID- 8261449
TI  - Subcellular localization of the bcl-2 protein in malignant and normal lymphoid
      cells.
AB  - The bcl-2 oncogene is expressed in lymphoid and myeloid cells as well as in
      neurons and several types of epithelial cells and inhibits programmed cell death
      (apoptosis). Deregulation by the t(14;18) translocation in lymphoid malignancies
      induces inappropriate cell survival and serves as one of the steps toward a fully
      malignant behavior. Using pre- and postembedding immunoelectron microscopy in
      normal and neoplastic lymphocytes, we demonstrate bcl-2 immunoreactivity to the
      mitochondrial outer circumference and the nuclear envelope and to a lesser degree
      to the cell membrane. Mitochondrial staining was patchy, reminiscent of
      mitochondrial contact zones. Additionally, there was a suggestion of association
      with nuclear pores. In these regions, transmembrane transport is mediated. This
      may suggest that bcl-2 exerts its function in this process.

PMID- 8261450
TI  - Role of activated protein C in facilitating basement membrane invasion by tumor
      cells.
AB  - The present study was undertaken to investigate the role of plasminogen activator
      inhibitor type 1 (PAI-1) and activated protein C (APC) in the regulation of tumor
      cell invasion. PAI-1 was purified in active form from conditioned medium of human
      umbilical vein endothelial cells under denaturing conditions (4 M guanidine-HCl).
      The purified inhibitor reacts with urokinase-type plasminogen activator (uPA) and
      APC. Two selected human lines, HOC-I (ovarian cancer cells) and SMT-ccl
      (choriocarcinoma cells), preferentially invaded through reconstituted basement
      membranes in an in vitro invasion assay using a modified Boyden chamber. The
      present study determined the efficacy of these two agents (PAI-1 and APC) used
      alone or in combination in inhibiting or facilitating tumor cell invasion. Active
      PAI-1 inhibited the tumor cell surface receptor-bound uPA activity. In an in
      vitro invasion assay, active PAI-1 reduced tumor cell invasive potential in a
      dose-dependent manner. When SMT-ccl cells saturated with uPA-PAI-1 complexes were
      treated with a 50-fold molar excess of APC, PAI-1-APC complex was demonstrated in
      conditioned medium, indicating that PAI-1 was dissociated from receptor-bound uPA
      on tumor cells and that tumor cell-associated uPA restored its enzymatic
      activity. Although APC alone had no effect on tumor cell invasion, the addition
      of APC to the cells saturated with uPA-PAI-1 complexes showed regeneration of
      tumor cell surface receptor-bound uPA activity and produced substantial and
      efficient invading effects. These data suggest that PAI-1 activity may be
      neutralized by APC or that APC may promote tumor cell invasion via inactivation
      of PAI-1 by formation of a stable PAI-1-APC complex. These observations suggest
      that APC may play a critical role in the initiation of a hematogenous metastatic
      process (extravasation step).

PMID- 8261451
TI  - Purification and characterization of a cell growth factor from a human leukemia
      cell line: immunological identity with ferritin.
AB  - We have succeeded in long-term cultivation of a human erythroleukemia cell line,
      K-562-T1 (T. Okabe, M. Fujisawa, and F. Takaku, Proc. Natl. Acad. Sci. USA, 81:
      453-455, 1984). The cells grown in a protein-free chemically defined medium have
      been shown to produce cell growth factors (A. Mihara et al., In Vitro Cell. Dev.
      Biol., 23: 317-322, 1987). In this study, we have purified a cell growth factor
      from the conditioned medium that stimulates the proliferation of human leukemia
      cells, HL-60. In the purified factor, two major protein bands of 24 kDa and 22
      kDa were identified on a sodium dodecyl sulfate-polyacrylamide gel. The 22 kDa
      protein was stained with a monoclonal antibody to the light chain of ferritin.
      The growth-promoting activity of the purified factor was coprecipitated with a
      monoclonal antibody to the light chain or heavy chain of human ferritin. These
      results suggest that K-562-T1 cells produce a cell growth factor that is related
      to ferritin.

PMID- 8261452
TI  - Vascular permeability factor gene expression in normal and neoplastic human
      ovaries.
AB  - Epithelial ovarian cancer is an aggressive malignancy with a generally poor
      outcome. To improve survival, novel therapeutic strategies for this disease are
      needed and require elucidation of the biological events that underlie
      transformation and tumor growth. Vascular permeability factor (VPF), also known
      as vascular endothelial growth factor, is a homodimeric glycoprotein that acts on
      vascular endothelium as a potent permeability-inducing agent and mitogen. The
      present study demonstrates for the first time the constitutive gene expression of
      VPF in normal and neoplastic human ovaries. Abundant levels of VPF have been
      identified by an immunoassay in the ascites of patients with epithelial ovarian
      cancer (K-T. Yeo et al., Cancer Res., 53: 2912-2918, 1993). We have identified
      the malignant epithelium as one source of VPF in the ascites. Reverse
      transcription-polymerase chain reaction has demonstrated the expression of the
      two secreted isoforms, VPF121 and VPF165, in normal and neoplastic ovaries.
      Western blotting and an endothelial cell proliferation assay confirmed secretion
      of a biologically active product. VPF may be an important mediator of ascites
      formation and tumor metastasis observed in neoplastic conditions of the ovary.

PMID- 8261453
TI  - Nuclear matrix proteins distinguish normal diploid osteoblasts from osteosarcoma
      cells.
AB  - Interrelationships between nuclear architecture and gene expression were examined
      by comparing the representation of nuclear matrix proteins in ROS 17/2.8 rat and
      MG-63 human osteosarcoma cells with those in normal diploid osteoblasts. The
      tumor-derived cells coexpress genes which are expressed in a sequential and
      mutually exclusive manner during the progressive stages of osteoblast
      differentiation. In osteosarcoma cells two-dimensional electrophoretic analysis
      indicates a composite representation of nuclear matrix proteins characteristic of
      both the proliferative and postproliferative periods of osteoblast phenotype
      development. In addition, nuclear matrix proteins unique to the tumor cells and
      the absence of nuclear matrix proteins found only in normal diploid osteoblasts
      are observed. Tumor-specific nuclear matrix proteins include those expressed in a
      proliferation-dependent and independent manner. There is a parallel relationship
      between nuclear matrix proteins and the expression of cell growth and tissue
      specific genes during osteoblast differentiation and in osteosarcoma cells where
      the developmental sequence of gene expression has been abrogated. Nuclear matrix
      proteins therefore provide markers reflecting defined periods of bone cell
      differentiation and phenotypic characteristics of an osteosarcoma.

PMID- 8261454
TI  - E-cadherin and alpha-catenin expression in human esophageal cancer.
AB  - Intercellular adhesion of the epithelial tissue is mainly regulated by the E
      cadherin (E-cad) molecule. alpha-Catenin (alpha-cat) is one of the E-cad
      associated cytoplasmic proteins that forms a linkage to the cytoskeleton and
      regulates E-cad function. To investigate the mechanism of dysfunction in cell
      cell adhesion in cancerous tissues, we examined E-cad and alpha-cat expression by
      immunohistochemical staining on 46 human esophageal cancers using our specific
      monoclonal antibodies. By grading of E-cad and alpha-cat expression as uniformly
      positive (+), heterogeneous (+/-), or uniformly negative (-), the 46 tumors could
      be classified into 9 (20%) E-cad(+)/alpha-cat(+), 15 (33%) E-cad(+/-)/alpha
      cat(+/-), 21 (46%) E-cad(+/-)/alpha-cat(-), and 1 (2%) E-cad(-)/alpha-cat(-).
      Twenty-five (54%) of the 46 tumors showed a similar expression of both molecules,
      while the other 21 tumors (46%) showed E-cad(+/-)/alpha-cat(-). Thus, although
      the expression of alpha-cat was significantly correlated with that of E-cad, in
      some tumors the reduction of alpha-cat was greater. Regarding the
      clinicopathological features, the reduction of alpha-cat expression, as well as
      that of E-cad, was significantly associated with tumor dedifferentiation,
      infiltrative growth, and lymph node metastasis (P < 0.01). Furthermore, the
      frequency of lymph node metastasis in E-cad(+/-)/alpha-cat(-) tumors was
      significantly higher (90%) than in E-cad(+)/alpha-cat(+) tumors (22%) (P < 0.01)
      or in E-cad(+/-)/alpha-cat(+/-) tumors (47%) (P < 0.05). These results suggest
      that not only E-cad but also alpha-cat are important regulators of intercellular
      adhesion and that alpha-cat is also involved in invasion and metastasis. In
      particular, reduction of alpha-cat expression is more correlated with invasive
      phenotype and lymph node metastasis than E-cad expression in human esophageal
      cancer.

PMID- 8261455
TI  - Fifth annual Pezcoller symposium: apoptosis.

PMID- 8261456
TI  - Correspondence re: B. Fernandes et al., beta 1-6 branched oligosaccharides as a
      marker of tumor progression in human breast and colon neoplasia. Cancer Res., 51:
      718-723, 1991.

PMID- 8261457
TI  - Mutation of K-ras protooncogene is associated with histological subtypes in human
      mucinous ovarian tumors.
AB  - A series of 57 mucinous and 47 serous ovarian tumors (adenomas, tumors of
      borderline malignancy, and carcinomas) were examined by polymerase chain reaction
      single strand conformation polymorphism analysis and direct sequencing for
      mutations in codons 12, 13, and 61 of K-ras gene. Higher incidence of K-ras
      mutations was observed in mucinous tumors compared to serous ones. Mutations were
      detected in 4 of 30 mucinous adenomas (13%), in 4 of 12 mucinous tumors of
      borderline malignancy (33%), and in 7 of 15 mucinous carcinomas (46%). Only 1 of
      17 serous carcinomas (6%) had a mutation of K-ras in serous ovarian tumors. All
      mutations identified were in codon 12. Detailed analysis revealed that more K-ras
      mutations in mucinous adenomas were observed in intestinal type (identified in 4
      of 13) than in endocervical type (identified in 0 of 17). Thus, K-ras gene codon
      12 mutations in mucinous ovarian adenomas appear to be associated with the
      occurrence of intestinal type adenomas.

PMID- 8261458
TI  - Intracellular glutathione levels regulate Fos/Jun induction and activation of
      glutathione S-transferase gene expression.
AB  - Induction of glutathione S-transferase Ya and NAD(P)H:quinone reductase gene
      expression by a variety of chemical agents is mediated by regulatory elements,
      EpRE and ARE, composed of two adjacent AP-1-like binding sites and activated by
      Fos/Jun heterodimeric complex (AP-1). Recent studies show that chemical induction
      of glutathione S transferase Ya and quinone reductase gene expression is
      associated with an induction of c-fos and c-jun gene expression and AP-1 binding
      activity. In this report we present evidence that the AP-1 binding activity and
      the expression of chloramphenicol acetyltransferase activity from an EpRE Ya-cat
      gene construct are induced by an increase in intracellular oxidant levels. We
      observe that lowering the glutathione levels with buthionine sulfoximine, an
      inhibitor of gamma-glutamylcysteine synthetase, or diamide, a thiol-oxidizing
      agent, stimulates both basal and chemical-inducible expression of chloramphenicol
      acetyltransferase activity from EpRE Ya-cat and the AP-1 binding activity.
      Furthermore, we observe that the induction of these activities by a variety of
      chemical agents is inhibited by thiol compounds N-acetylcysteine and glutathione.
      These findings suggest that diverse chemicals that induce the AP-1 complex,
      leading to the AP-1-mediated transcriptional activation of glutathione S
      transferase Ya gene expression, may act through a common mechanism involving the
      production of reactive oxygen species and depletion of reduced glutathione.

PMID- 8261459
TI  - Alterations of (CA)n DNA repeats and tumor suppressor genes in human gastric
      cancer.
AB  - We have examined whether alterations of simple (CA)n DNA repeats, as observed in
      human colon cancers, occur during human gastric carcinogenesis and whether such
      alterations reflect genomic instability that could lead to other genetic changes.
      A total of 22 gastric cancer samples were analyzed: 15 well or moderately
      differentiated adenocarcinomas, 6 signet-ring cell carcinomas, and 1 poorly
      differentiated adenocarcinoma. When (CA)n repeat sequences were examined at 10
      loci, one adenocarcinoma showed a loss of repeat sequences at five loci, three
      adenocarcinomas gained a repeat at one locus, and one adenocarcinoma had new,
      repeated sequences at five loci. Three samples showed mutations in the p53 gene,
      two in exon 5 (both GC to AT transition at a CpG dinucleotide) and one in exon 7
      (AT to GC transition). Only one sample with a p53 mutation also showed altered
      (CA)n repeats. A putative tumor suppressor gene, connexin 32, was not altered as
      assessed by single-strand conformation polymorphism analysis. These results
      suggest that genomic instability revealed by (CA)n repeat changes does not seem
      to contribute to induction of point mutations in p53 or connexin 32 genes but may
      participate in loss of heterozygosity at APC/MCC loci. The results are consistent
      with the hypothesis that different mechanisms are involved in the gain and loss
      of (CA)n repeats.

PMID- 8261460
TI  - Analysis of the neurofibromatosis 2 gene in human ependymomas and astrocytomas.
AB  - Ependymomas and astrocytomas commonly have allelic losses of chromosome 22q,
      which suggests the presence of a glioma tumor suppressor gene on 22q. A candidate
      tumor suppressor gene on 22q is the neurofibromatosis 2 (NF2) gene since NF2
      patients have an increased susceptibility to ependymomas and astrocytomas. Using
      single strand conformation polymorphism analysis and direct DNA sequencing, we
      screened 8 ependymomas and 30 fibrillary astrocytomas from non-NF2 patients for
      mutations in the coding sequence and portions of the 3' untranslated region of
      the NF2 gene. Only one mutation was detected, a single base deletion in NF2 exon
      7 from a spinal ependymoma, which had also lost the wild-type allele. These
      results suggest that the NF2 gene may be important in the formation of some
      ependymomas but the NF2 gene is probably not the critical chromosome 22q tumor
      suppressor gene involved in astrocytoma tumorigenesis.

PMID- 8261461
TI  - Western blotting and enzymatic activity analysis of cathepsin D in breast tissue
      and sera of patients with breast cancer and benign breast disease and of normal
      controls.
AB  - Increased total antigen amounts of cathepsin D in breast tissue have been
      reported to be associated with increased disease recurrence, more frequent
      metastasis, and increased mortality in breast cancer patients. In the present
      study, Western blotting analysis has been used for the first time to determine
      the relative amounts of precursor and processed forms of cathepsin D in sera and
      breast tissue of patients with breast cancer, benign breast disease, and normal
      controls. Sera gave similar blots for breast cancer patients and controls with
      two major forms of cathepsin D (M(r) 52,000 and 27,000). Malignant breast tissue
      contained the two forms of cathepsin D found in sera and an additional M(r)
      31,000 form which was found in significantly increased (P < 0.001) relative
      amounts in breast tissue from 43 breast cancer patients [24 +/- 12% (SD)] when
      compared to 51 benign breast disease patients (13 +/- 8.9%) and 23 normal
      controls (1.8 +/- 4.4%). Preliminary analysis of subgroups of benign breast
      disease patients suggested no significant difference (P = 0.41) in relative
      amounts of the M(r) 31,000 form of cathepsin D between proliferative-type and non
      proliferative-type fibrocystic breast disease. A cathepsin D assay has been
      optimized for human breast tissue and used to demonstrate for the first time
      significantly increased (P < 0.001) amounts of pepstatin-inhibitable, cathepsin D
      specific activity in breast tissue from 36 breast cancer patients (2.2 +/- 1.4
      units/mg of protein) when compared to 47 benign breast disease patients (0.63 +/-
      0.43) and 23 normal controls (0.24 +/- 0.21). Preliminary analysis of subgroups
      of benign breast disease patients suggested no significant difference (P = 0.21)
      in pepstatin-inhibitable, cathepsin D-specific activity between proliferative
      type and nonproliferative-type fibrocystic breast disease. The positive
      correlation (r = 0.82) of increased amounts of the M(r) 31,000 form of cathepsin
      D and increased pepstatin-inhibitable, cathepsin D enzymatic activity in
      malignant breast tissue suggests that the M(r) 31,000 form is the proteolytically
      active form of the enzyme which may be involved in the development and/or
      metastatic spread of breast cancer.

PMID- 8261462
TI  - Increase of fucosylated serum cholinesterase in relation to high risk groups for
      hepatocellular carcinomas.
AB  - Serum cholinesterase (ChE) (E.C. 3.1.1.8) is a glycoprotein which has 36
      potential sites of asparagine-N-linked sugar chains. The structures of
      oligosaccharides released from ChE on hydrazinolysis were studied by serial
      lectin affinity column chromatography, exoglycosidase digestion, and methylation
      analysis. Seventy-three % of the sugar chains occurred as biantennary
      oligosaccharides and the remainder as C-2 and C-2,4/C-2,6 branched tri- and
      tetraantennary oligosaccharides. Several percentages of the Lewis X antigenic
      determinant and fucosylated mannose core were linked to them, and their sialic
      acid residues were linked to nonreducing terminal galactose residues at the C-3
      and C-6 positions. Aleuria aurantia lectin-reactive ChE with the Lewis X
      antigenic determinant increased in hepatocellular carcinomas and liver cirrhosis
      compared with chronic hepatitis; on the other hand, Aleuria aurantia lectin
      reactive ChE did not change significantly after transcatheter arterial
      embolization and was not related to the serum levels of alpha-fetoprotein and
      carcinoembryonic antigen in patients with hepatocellular carcinomas. Accordingly,
      the analysis of Aleuria aurantia lectin-reactive ChE is clinically useful for
      differentiating liver cirrhosis from chronic hepatitis and to identify high risk
      groups for hepatocellular carcinomas, i.e., cirrhotic patients in Child's A
      grade.

PMID- 8261463
TI  - Expression of bcl-2 in small cell lung carcinoma cells.
AB  - We have investigated the expression of bcl-2 protein in a panel of small cell
      lung carcinoma (SCLC) cells lines. Five of six cell lines examined expressed
      relatively high levels of bcl-2 protein and transcripts. The bcl-2 expression in
      SCLC cells, however, was not always associated with myc expression. Since
      dysregulation of bcl-2 may be involved in the course of tumorigenesis and/or in
      the acquisition of drug resistance of tumor cells, the expression of bcl-2 in
      SCLC cells may become an important indicator in the prognosis or treatment of
      SCLC.

PMID- 8261464
TI  - Dioxin-responsive genes: examination of dose-response relationships using
      quantitative reverse transcriptase-polymerase chain reaction.
AB  - The purpose of the present experiments was to examine dose-response relationships
      for induction of hepatic mRNA following a single administration of 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) to rats. The induction of cytochrome P450-1A1
      (CYP1A1) mRNA is compared to other "dioxin-responsive" genes including UDP
      glucuronosyltransferase I, plasminogen activator inhibitor 2, and transforming
      growth factor alpha using a sensitive reverse transcriptase-polymerase chain
      reaction-based method. Sample-to-sample variability in amplification is a concern
      in using polymerase chain reaction to quantitate biological responses. However,
      in the present study recombinant RNA templates were synthesized to use as
      internal standards in both the reverse transcription and the polymerase chain
      reaction steps. The induction of CYP1A1 mRNA was extremely sensitive to TCDD
      treatment with increases observed at doses as low as 1 ng/kg body weight. The
      induction of CYP1A1 mRNA correlated highly (R2 > 0.90) with an increase in
      ethoxyresorufin-o-deethylase activity, a CYP1A1-associated enzyme activity.
      However, induction of CYP1A1 mRNA levels was detected at lower TCDD doses than
      was ethoxyresorufin-o-deethylase activity, reflecting the greater sensitivity of
      the reverse transcription-polymerase chain reaction approach to detect
      transcriptional activation of the CYP1A1 gene. UDP-glucuronosyltransferase I mRNA
      was increased over control (5-fold) but required 1000-times higher TCDD doses (1
      microgram/kg) to result in a significant increase than did CYP1A1. Plasminogen
      activator inhibitor 2 and transforming growth factor alpha mRNA, both previously
      shown to be induced by TCDD in human keratinocytes, were not increased in rat
      liver. Hence, these studies reaffirm that TCDD acts through classical receptor
      mechanisms with gene-to-gene differences in responsiveness. The reverse
      transcription-polymerase chain reaction method developed to measure mRNA for
      dioxin-responsive genes in rat liver will allow for measuring multigene and
      tissue responses to TCDD and other xenobiotics with high sensitivity,
      reproducibility, and adaptability and should increase our understanding of
      various dose-response relationships.

PMID- 8261465
TI  - Effect of tamoxifen on carbachol-triggered intracellular calcium responses in
      chicken granulosa cells.
AB  - The effect of the nonsteroidal antiestrogen tamoxifen on carbachol (CCh)
      triggered intracellular Ca2+ surges was determined in granulosa cells from the
      two largest preovulatory follicles of laying hens. The intracellular calcium ion
      concentration ([Ca2+]i) was measured in cells loaded with the Ca(2+)-responsive
      fluorescent dye fura-2. Resting [Ca2+]i was 96 +/- 5 nM (n = 20), and CCh (1 mM)
      triggered a large initial [Ca2+]i spike to 600-800 nM, due to the mobilization of
      Ca2+ from internal stores. Following the spike, the [Ca2+]i dropped to a lower,
      suprabasal level with super-imposed oscillations, which depended on Ca2+ influx,
      and returned to the resting level by 2 to 4 min. Tamoxifen (10 microM) did not by
      itself affect [Ca2+]i but pretreating granulosa cells with tamoxifen (10 microM)
      prolonged the CCh-triggered [Ca2+]i surge and oscillations by as much as 10 to 30
      min. Pretreatment with much higher concentrations of tamoxifen (e.g., 0.5 mM)
      also had no effect by themselves, but caused a prolonged rise in [Ca2+]i
      following CCh (1 mM) stimulation. The effect of tamoxifen on CCh-triggered
      [Ca2+]i responses was mimicked by the tamoxifen metabolite 4-hydroxytamoxifen (10
      microM), but not by the structurally related antiestrogens nafoxidine (10 microM)
      or clomiphene citrate (10 microM). The tamoxifen effect on the CCh-triggered
      [Ca2+]i response was not mediated through estrogen receptors since pretreating
      granulosa cells with 17 beta-estradiol (10(-6) M) did not mimic the tamoxifen
      response. The effect of tamoxifen was inhibited by pretreating granulosa cells
      with the Ca2+ channel blocker, lanthanum (1 mM), or by incubating the cells in
      Ca(2+)-free medium. Tamoxifen did not affect [Ca2+]i surges triggered by 17 beta
      estradiol (10(-6) M) or dimethyl sulfoxide (1%) which mobilize Ca2+ from internal
      stores. Pretreating granulosa cells with tamoxifen (10 microM) or 4
      hydroxytamoxifen (10 microM) before inducing Ca2+ influx through voltage
      dependent Ca2+ channels by depolarizing the cells with 45 mM external K+, caused
      a prolonged rise of [Ca2+]i, with oscillations, similar to the CCh response.
      These studies demonstrate that tamoxifen affects the activation of chicken
      granulosa cell Ca2+ channels by CCh or by raising the external K+ concentration,
      resulting in a prolongation of the sustained [Ca2+]i elevation and oscillations,
      which result from the influx of extracellular Ca2+. These observations suggest
      that tamoxifen interacts with open Ca2+ channels in chicken granulosa cells and
      keeps them open for prolonged periods of time.

PMID- 8261466
TI  - Inhibition of microtubules and cell cycle arrest by a new 1-deaza-7,8
      dihydropteridine antitumor drug, CI 980, and by its chiral isomer, NSC 613863.
AB  - CI 980 (NSC 613862; [S-(-)]) and NSC 613863 [R-(+)] are the two chiral isomers of
      ethyl 5-amino 1,2-dihydro-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7-ylcar bamate
      (NSC 370147), which is a mitotic inhibitor with in vivo and in vitro activity
      against murine multidrug-resistant sublines. We have characterized the inhibition
      of in vitro microtubule assembly by the S (CI 980) and R (NSC 613863)
      enantiomers, their actions on the cytoplasmic microtubule network of epithelial
      like PtK2 cells, and on the cell cycle of different human and murine leukemias
      and PtK2 cells. Assembly of purified tubulin, or tubulin plus microtubule
      associated proteins, into microtubules was substoichiometrically inhibited by
      both compounds, which also induced a slow depolymerization of preassembled
      microtubules. Half inhibitory concentrations were 0.4-0.7 microM and 1.6-2.1
      microM for the S and R isomers, respectively. Excess of both drugs induced
      polymerization of liganded tubulin into abnormal polymers similar to colchicine.
      The cytoplasmic microtubules of PtK2 cells were disrupted by both compounds in a
      concentration- and time-dependent manner, which was observed by indirect
      immunofluorescence microscopy and quantified by an enzyme-linked immunoassay of
      cytoskeletal tubulin. Half inhibitory concentrations were 6 nM S isomer, 100 nM R
      isomer, and 1 microM colchicine. Twenty nM S isomer or 500-700 nM R isomer gave
      nearly maximal effect. At these concentrations, half maximal microtubule
      depolymerization took place after 2 h of treatment. After drug removal, slow
      microtubule assembly and nearly complete reorganization of the cytoplasmic
      microtubules of PtK2 cells were observed (24 h). One nM S enantiomer or 25 nM R
      enantiomer induced mitotic arrest in 8 h in U937, HL60, and EL4 leukemias. PtK2
      cells also stopped in mitosis after a 24-h incubation with 50 nM R isomer or 5 nM
      S isomer. The inhibition of cell division was irreversible in the leukemic cells,
      while PtK2 cells partially resumed growth. Although the interactions of CI 980
      with microtubules in vitro are not very different from other drugs, it is a most
      potent cellular microtubule and mitotic inhibitor.

PMID- 8261467
TI  - Tn antigen is expressed on leukosialin from T-lymphoid cells.
AB  - Various T-lymphoid cells were labeled with [3H] glucosamine and then cell lysates
      were prepared from them. The Tn antigen was immunoprecipitated and analyzed by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by
      fluorography. The Tn antigen was found to be expressed on leukosialin, a major
      glycoprotein of T-lymphoid cells. The carbohydrate moieties of leukosialin were
      isolated from Jurkat and Molt 4 cells by alkaline borohydride treatment. The
      leukosialin in both cases predominantly contained single N-acetylgalactosamine
      residues, consistent with expression of the Tn antigen. Tryptic glycopeptides
      containing antigenic sites were isolated using an MLS 128 immunoaffinity column
      and purified by gel filtration and reverse phase column chromatographies.
      Sequence analyses revealed that all the glycopeptides obtained contained three
      consecutive residues of N-acetylgalactosamine-Ser/Thr, supporting the idea that
      the epitopic structure is a cluster of N-acetylgalactosamine-Ser/Thr.

PMID- 8261468
TI  - CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate
      carcinogens is their major route of metabolism in humans.
AB  - The contribution of CYP1A2 to the metabolism of the dietary heterocyclic amines,
      2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline (MeIQx) in vivo in humans, has been determined
      with furafylline, a highly selective inhibitor of this enzyme. The inhibitory
      potential of furafylline in vivo was first assessed by determining its effect on
      clearance of phenacetin to paracetamol by the model CYP1A2-dependent O
      deethylation pathway. Furafylline inhibited this reaction by > 99% in all
      subjects, thus demonstrating its applicability to determining the contribution of
      CYP1A2 to a given reaction in vivo. A group of 6 healthy male volunteers received
      either placebo or 125 mg furafylline, in a double-blind balanced crossover
      design, 2 h prior to consuming a test meal of fried beef containing a known
      amount of amines. The excretion of PhIP and MeIQx in urine was determined during
      the subsequent 28 h, using gas chromatography-mass spectrometry. Following
      furafylline, the excretion of unchanged MeIQx increased 14.3-fold, while that of
      PhIP increased 4.1-fold (P < 0.01, paired t test). Elimination of both amines was
      first order and very rapid, with half-lives of < 5 h. The elimination rate
      constants did not change following furafylline, suggesting that total clearance
      is limited by hepatic blood flow. Because the elimination of the amines was first
      order, it was possible to calculate the contribution of CYP1A2 to the clearance
      of the amines. CYP1A2-catalyzed metabolism accounts for 91% of the elimination of
      ingested MeIQx and 70% of ingested PhIP, most likely via N-hydroxylation.

PMID- 8261469
TI  - Mechanism of the antiproliferative effect of milk mineral and other calcium
      supplements on colonic epithelium.
AB  - Recently we have shown that supplemental dietary calcium precipitates luminal
      cytolytic surfactants and thus inhibits colonic epithelial proliferation, which
      may decrease the risk of colon cancer. In Western diets, milk products are
      quantitatively the most important source of dietary calcium. However, they also
      contain large amounts of phosphate, which has been hypothesized to inhibit the
      antiproliferative effect of calcium. Therefore, we studied in rats the possible
      differential antiproliferative effects of dairy calcium, calcium carbonate, and
      calcium phosphate, supplemented to a Western high-risk control diet. We observed
      that fecal bile acid excretion was similar in the various diet groups, whereas
      fatty acid excretion was stimulated by the calcium supplements in the order
      calcium carbonate > calcium phosphate > milk mineral. In fecal water,
      concentrations of bile acids and fatty acids were drastically decreased in the
      supplemented groups, resulting in decreased cytolytic activity of fecal water. In
      vitro incubation of fecal water from the control group with insoluble calcium
      phosphate also decreased the high concentrations of surfactants and their
      cytolytic activity. The response of the colonic epithelium to these primary
      luminal effects of calcium was a decrease in cell damage and cell proliferation.
      Only minor differences between the supplements were observed. The concentration
      of serum gastrin, the possible trophic effect of which could counteract the
      antiproliferative effect of calcium, was increased by the supplements, but no
      significant correlation was observed between serum gastrin concentration and
      epithelial proliferation. We conclude that dietary calcium precipitates luminal
      surfactants and thus inhibits cytolytic activity, epithelial cell damage, and
      colonic proliferation. The similar efficacy of calcium carbonate, calcium
      phosphate, and milk mineral indicates that the antiproliferative effect of milk
      mineral is mediated by its calcium content and is not inhibited by phosphate.

PMID- 8261470
TI  - Unity for quality--from a Christian perspective.

PMID- 8261471
TI  - Coping with pressure and tension.

PMID- 8261472
TI  - Facing stress.

PMID- 8261473
TI  - When the helper needs help.

PMID- 8261474
TI  - Professor Jan J. Kellerman (1926-1993).

PMID- 8261475
TI  - The challenge of maintaining coronary arterial patency with intravenous heparin
      following tissue plasminogen activator administration.
AB  - It is widely accepted that coronary arterial patency, achieved early after
      symptom onset and maintained over time, is an absolute prerequisite for patient
      benefit following thrombolytic therapy. Conjunctive pharmacological agents such
      as heparin appear to play an important role in maintaining vessel patency,
      particularly following tissue plasminogen activator (t-PA) administration.
      Unfortunately, dosing strategies and monitoring have not kept pace with the rest
      of the field. Further investigation is encouraged.

PMID- 8261476
TI  - Reversible catecholamine-induced cardiomyopathy presenting as acute pulmonary
      edema in a patient with pheochromocytoma.
AB  - Cardiac injury caused by elevated levels of circulating catecholamines is a well
      known phenomenon. We report a patient who, secondary to transient regional left
      ventricular dysfunction (despite normal coronary arteries), developed acute
      pulmonary edema. Echocardiography showed marked anteroapical hypokinesia and an
      apical thrombus. The diagnosis of pheochromocytoma was made by plasma
      catecholamine levels, abdominal ultrasound and finally at operation. The patient
      recovered completely long before surgical intervention was undertaken.

PMID- 8261477
TI  - Postexercise syncope: evidence for increased activity of the sympathetic nervous
      system.
AB  - This report describes an association of postexertional syncope with increased
      levels of circulating catecholamines. A 36-year-old male who experienced
      postexercise bradycardia and asystole had higher basal plasma norepinephrine (120
      versus 68 +/- 6 pg/ml) and epinephrine (18 versus less than 10 pg/ml) but a
      similar vagal tone (vagal tone index of 5.44 versus 5.81 +/- 1.00 U) when
      compared with 6 closely matched subjects who underwent an uneventful stress test.

PMID- 8261478
TI  - Fulminant amyloid cardiomyopathy.
AB  - Within a 3-month period, a 71-year-old man went from an asymptomatic, active
      existence to intractable heart failure and death. Widespread amyloid deposition
      was noted on the histologic examination of endomyocardial biopsy samples. The
      historical and laboratory features of this patient's rapidly devastating clinical
      course form the basis of this report.

PMID- 8261479
TI  - Aortic dissection due to discontinuation of beta-blocker therapy.
AB  - beta-Blockers are known to protect a vulnerable aorta from acute dissection, as
      well as reducing the risk of recurrent dissection. This case presentation reports
      the history of a 60-year-old male suffering from acute aortic dissection
      following discontinuation of beta-blocker therapy. The patient has shown arterial
      hypertension for about 20 years treated solely by beta-blockers. Two days after
      stopping the use of metoprolol, a nonselective beta 1-blocker without ISA, the
      patient developed severe chest pain during exercise. Diagnosis of type I-aortic
      dissection according to DeBakey was achieved by transthoracal echocardiography
      and computed tomography. Successful surgery by replacement of the ascending aorta
      was performed about 1 h following admission to the intensive care unit. During
      the procedure, tamponade of the left ventricle occurred followed by cardiogenic
      shock. Postoperative management was complicated by prolonged respiratory therapy
      and acute gastrointestinal bleeding; 1-year follow-up showed no evidence of
      disease. Thus, in this case acute dissection may be the consequence of
      discontinuing the use of metoprolol, possibly due to uncontrolled hypertension or
      specific response to the beta-blocker.

PMID- 8261480
TI  - Pericardial color Doppler flow in postpericardiotomy effusive constrictive
      pericarditis.
AB  - A laminar color Doppler flow was discovered in the pericardial space in a 35-year
      old man with postpericardiotomy effusive constrictive pericarditis. The flow was
      detected by transesophageal color Doppler echocardiography. A further pulsed
      Doppler study revealed a to-and-fro flow, which was synchronized with the cardiac
      rhythm. We hypothesized that this flow was generated by the rhythmic cardiac
      contraction. It was then augmented by hard fibrous pericardium and became
      detectable by color Doppler echocardiography. Pericardial effusion is a frequent
      echocardiographic finding but little attention has been paid to the flow in it.
      The laminar flow in the pericardial space in our patient is related to his hard
      pericardium and can aid in making the diagnosis of effusive constrictive
      pericarditis. We suggest that flow in the pericardial space deserves more
      attention and may provide valuable diagnostic aid.

PMID- 8261481
TI  - A case of torsade de pointes occurring in a newborn with persistent 2:1
      atrioventricular block.
AB  - A case of QT interval prolongation with ventricular tachycardia and torsade de
      pointes is reported. Arrhythmias occurred in a baby with persistent 2:1
      atrioventricular block and long QT interval 2 days after birth and were self
      limiting. No structural cardiac defect was present. Serum levels of sodium,
      potassium, magnesium and calcium were in the normal range. Finally, the
      pathogenetic mechanism of cardiac block is discussed.

PMID- 8261482
TI  - The hemodynamic and prognostic significance of echo-Doppler-proven mitral
      regurgitation in patients with dilated cardiomyopathy.
AB  - Data from cardiac catheterization at rest and during exercise in 57 patients with
      dilated cardiomyopathy (DCM) were analyzed to evaluate the bearing of mitral
      regurgitation (MR) detected by color Doppler echocardiography (CDE) on
      prognostically important invasive hemodynamic parameters and survival. The
      etiology of DCM was coronary artery disease in 21 patients and unproven
      ('idiopathic') in 36 patients. MR was detected by CDE in 34 patients (60%) with
      an agreement of 93% compared to left ventriculography. Mean age, etiology of DCM
      and duration of symptoms were similar in patients with and without MR, while
      patients with MR were in a higher NYHA class, had lower ejection fraction (LVEF)
      (25 +/- 13 vs. 35 +/- 17%; p < 0.02), larger left ventricular volumes (356 +/-
      138 vs. 268 +/- 61 ml; p < 0.01) and higher left ventricular end-diastolic
      pressure (LVEDP) (21 +/- 9 vs. 13 +/- 7 mm Hg; p < 0.01). At rest, right-sided
      pressures were higher in patients with MR compared to patients without MR
      (pulmonary wedge pressure 20 +/- 9 vs. 10 +/- 3 mm Hg, mean pulmonary arterial
      pressure 30 +/- 11 vs. 20 +/- 8 mm Hg, mean right atrial pressure 9 +/- 4 vs. 4
      +/- 2 mm Hg, all p < 0.001), but no significant differences were found in cardiac
      index (CI) or stroke index (SI).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261483
TI  - Pulmonary function tests in patients with congestive heart failure: effects of
      medical therapy.
AB  - In a group of 13 patients with severe heart failure, both forced vital capacity
      (FVC) and forced expiratory volume in 1 s (FEV1) significantly improved after
      intensive medical therapy (FVC: from 77 +/- 17 to 92 +/- 20%, p < 0.001; FEV1:
      from 65 +/- 15 to 81 +/- 15%, p < 0.001) in the absence of change in M-mode echo
      cardiac dimension and left ventricular systolic function; on the other hand, a
      change of indices of left ventricular filling by Doppler transmitral flow was
      documented (E/A ratio: from 3.6 +/- 1.2 to 1.65 +/- 1.5, p < 0.01; early filling
      deceleration time: from 94 +/- 39 to 178 +/- 78 ms, p < 0.01), indicating a
      reduction of pulmonary capillary pressure; this probably positively affected
      pulmonary interstitial edema and bronchial wall congestion, thus enhancing
      pulmonary function.

PMID- 8261484
TI  - Pharmacological blockade of platelet GPIIb/IIIa and the inherited disorders of
      the platelet GPIIb/IIIa (Glanzmann's thrombasthenia): how safe is this
      antithrombotic approach for both acute and chronic treatment of thromboembolic
      disorders? Brief communication.

PMID- 8261485
TI  - Role of the circulating and tissue-based renin-angiotensin system in the
      development of heart failure: implications for therapy.
AB  - The renin-angiotensin system (RAS) is believed to play a central role in the
      pathophysiology of heart failure. However, there is a wide variability in plasma
      renin levels in patients with heart failure, and normal plasma renin activity has
      been documented in patients with mild or compensated disease. Recent evidence has
      demonstrated the existence of endogenous RAS in a number of tissues associated
      with cardiovascular homeostasis. It is possible that these tissue RAS are
      activated in the early stages of heart failure when plasma renin activity is
      normal, and therefore contribute to the progression of this condition.
      Angiotensin-converting enzyme (ACE) inhibitors reduce both circulating and tissue
      RAS activity. They are of symptomatic benefit and reduce the mortality associated
      with heart failure. A number of large studies initiated to investigate the
      effects of the ACE inhibitor enalapril in patients with all degrees of heart
      failure have been published recently. These studies show that addition of this
      drug to therapy significantly decreases patient morbidity and mortality, an
      effect which is most likely due to the suppression of circulating and tissue RAS
      activity this agent affords. The relationship of the profile of hormonal
      suppression seen with enalapril and drug dosage to observed beneficial effects on
      morbidity or mortality is unclear. Given the large range of alternative ACE
      inhibitors available, their variable structure, potency and duration of action,
      the potential for differences between agents needs further consideration.
      Although direct comparative studies are rare, there is a body of work suggesting
      that such differentiation may be present and may be of clinical significance.

PMID- 8261486
TI  - Detection of enteroviral genome and its significance in cardiomyopathy.
AB  - Myocarditis is an important disease that can lead to dilated cardiomyopathy
      (DCM). Using the polymerase chain reaction (PCR), we examined whether viral
      genomes were present specifically in the hearts of viral myocarditis or DCM
      patients in our autopsy series and compared the results with their
      clinicopathological features. We applied three different criteria of myocarditis
      to fully describe the histological features. The presence of a viral genome was
      detected by PCR but was not specific in DCM or myocarditis. PCR might be helpful
      in the diagnosis of viral myocarditis, when combined with other clinical
      information.

PMID- 8261487
TI  - Hypersensitivity of inner medullary collecting duct cells to arginine vasopressin
      and forskolin in cardiomyopathic hamsters.
AB  - Circulating arginine vasopressin (AVP) levels are elevated in congestive heart
      failure (CHF). However, the second messenger changes of the AVP system in CHF
      have not been explored. The aim of the present study is to determine whether
      there are changes in cAMP production in the AVP system in CHF. Cardiomyopathic
      hamsters of strain UM-X7.1 were used. Normal Golden Syrian hamsters were used as
      controls. IMCD cells were isolated from both group of hamsters. cAMP accumulation
      experiments were performed with AVP and forskolin stimulation in vitro. There was
      more cAMP release after stimulation by both AVP and forskolin in the
      cardiomyopathic than normal hamster IMCD cells. This illustrates that
      hypersensitivity of IMCD cells to AVP exists in cardiomyopathic hamsters. This
      may be partly explained by the presence of V2 receptor adenylate cyclase
      hyperactivity. The hypersensitivity of IMCD cells to AVP may be one of the
      factors causing fluid retention in CHF.

PMID- 8261488
TI  - Extent of increase in intracellular calcium concentration in electrically
      stimulated chick embryo heart cells does not depend on resting intracellular
      calcium concentration.
AB  - Using Fura-2 digital imaging microscopy, we found two cell populations in chick
      embryo heart with different resting intracellular calcium concentration
      ([Ca2+]i). Electrical stimulation of the cells led to the same increase in
      [Ca2+]i in both cell types, e.g. from 118 +/- 24 nM up to a peak of 243 +/- 67 nM
      (SD, n = 18) and from 44 +/- 15 nM up to a peak of 135 +/- 59 nM (SD, n = 13) in
      cells with high and low resting [Ca2+]i, respectively. All the cells showed the
      same rate of decline in [Ca2+]i. Due to synchronic stimulation and contraction,
      this method is suitable to measure [Ca2+]i transients at a high time resolution
      in individual cells.

PMID- 8261489
TI  - The effect of pure right ventricular ischemia on right and left ventricular
      performance in the anesthetized dog.
AB  - This study was planned to investigate the effect of ischemic dysfunction of the
      free wall of the right ventricle on right and left ventricular performance in the
      presence of a normally contracting interventricular septum. The experiments were
      performed in 6 anesthetized dogs in which echocardiogram, electrocardiogram,
      aortic blood pressure and left and right ventricular pressure were recorded. In
      the dog, the contractility of the septum is not affected by the occlusion of the
      right coronary artery which does not perfuse this part of the myocardium.
      Complete occlusion of the major individual ventricular branches and partial
      occlusion of the main right coronary artery did not impair right ventricular
      performance. Only complete occlusion of the main artery affected right and left
      ventricular function as revealed by echocardiogram. Reduced output by the
      ischemic right ventricle caused a reduction in left ventricular diastolic and
      systolic dimensions and in left ventricular developed pressure without any effect
      on left ventricular end-diastolic pressure.

PMID- 8261490
TI  - Effect of body characteristics on the variables of signal-averaged
      electrocardiogram in healthy teenage subjects.
AB  - Ventricular late potentials are obtained by signal-averaged surface
      electrocardiography. Late potentials have been reported to be affected by body
      characteristics or left ventricular mass. To evaluate late potentials in relation
      to body characteristics, 52 healthy Japanese young volunteers (21 girls, 31 boys)
      aged 15-16 years were studied. QRS duration in men was significantly longer than
      in women. There were no significant differences in low-amplitude signal and root
      mean square voltage between women and men. When relations between signal-averaged
      electrocardiographic parameters and body characteristics were examined, QRS
      duration had positive linear correlations with weight and body mass index. The
      slope of QRS duration and weight relation, and QRS duration and body mass index
      relation was significantly steeper in men compared to those in women; a
      prolongation of QRS duration in men compared to women as weight and body mass
      index increased. Our results indicated that QRS duration in teenage healthy
      subjects should be used with caution because it is affected by gender.

PMID- 8261491
TI  - Left ventricular mass regression and diastolic function improvement in mild and
      moderate hypertensive patients treated with lisinopril.
AB  - Thirty patients (18 male), mean age 49.5 +/- 6.3 years, were treated with
      lisinopril 10-40 mg once daily for 16 weeks. The effect of treatment on left
      ventricular mass and improvement in left ventricular diastolic function (measured
      by echo-Doppler) was assessed. Blood pressure changes were measured
      conventionally in the clinic and by ambulatory blood pressure monitoring. Clinic
      blood pressure decreased from 168.3 +/- 13.8/105.5 +/- 5.4 mm Hg to 137.5 +/-
      4.1/88.8 +/- 4.1 mm Hg (p < 0.005 for both systolic and diastolic blood
      pressures), and the heart rate from 75.2 +/- 3.7 to 74.4 +/- 7.6 beats per minute
      (NS). The frequency of ambulatory systolic blood pressure values > 140 mm Hg
      decreased in percentage from 63.3 +/- 12.8 to 29.9 +/- 9.1% (p < 0.005) and the
      frequency of ambulatory diastolic blood pressure values > 90 mm Hg decreased in
      percentage from 61.1 +/- 12.8 to 28.6 +/- 7.5% (p < 0.005). Septal and left
      ventricular posterior wall thickness decreased from 11.2 +/- 0.9 to 10.3 +/- 0.6
      mm and from 10.9 +/- 0.9 to 10.1 +/- 0.6 mm, respectively (both p < 0.005). Left
      ventricular diastolic diameter and the shortening fraction did not change
      significantly. Left ventricular mass, calculated from left ventricular wall
      thickness and diastolic diameter, decreased from 132.6 +/- 11.5 to 119.9 +/- 6.3
      g/m2 (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261492
TI  - Impact on survival of a decade of change in the management of patients who have
      sustained a myocardial infarction.
AB  - The survival of 906 consecutive patients who had sustained an acute myocardial
      infarction was monitored between the beginning of week 2 and the end of week 52.
      Deaths which occurred during this period were successfully predicted in terms of
      just 6 features; namely the value of left ventricular systolic time intervals
      measured during the 1st week, the occurrence of a myocardial infarction prior to
      the current hospitalisation, the patient's age, the coexistence of diabetes
      mellitus, the presence of left or right bundle branch blocks, and the
      administration of a diuretic agent while the patient was in hospital. By means of
      stepwise linear discriminant analysis predictions of mortality among the first
      302 patients based upon these 6 features were 80% specific and 63% sensitive.
      Prognostic features derived from the first 302 patients were then used to predict
      mortality among the remaining 604 patients. Observed and predicted mortalities
      were similar for both sets of patients. Although mortality was similar, the 604
      latter patients had received a considerably more interventional style of
      management than patients in the former group. Possible reasons for this failure
      of a change of management to improve prognosis are discussed.

PMID- 8261493
TI  - Comparative efficacy of thrombolytic therapy for acute myocardial infarction in
      patients with and without chronic preinfarction angina.
AB  - To resolve the question of whether coronary thrombolysis for acute myocardial
      infarction is more effective in patients with or in those without chronic
      preinfarction angina, we retrospectively analyzed cineventriculograms in 54
      patients with the first anterior Q-wave myocardial infarction during the chronic
      stage of myocardial infarction. Patients were divided into 2 groups according to
      the presence (group A, n = 24) or absence (group B, n = 30) of chronic
      preinfarction angina. In group A, 16 had either intracoronary (n = 6) or
      intravenous (n = 10) coronary thrombolysis with urokinase within 6 h after the
      onset of acute myocardial infarction. In group B, 11 had either intracoronary (n
      = 4) or intravenous (n = 7) coronary thrombolysis within 6 h after the onset of
      acute myocardial infarction. Global left ventricular ejection fraction and
      regional wall motion in infarct areas were evaluated quantitatively. In group A,
      the percentage of systolic segment shortening in infarct areas was 20 +/- (SD)
      16% in patients with thrombolytic therapy and 17 +/- 15% in those with
      conventional therapy (p = NS). By contrast, in group B, the regional wall motion
      in infarct areas was significantly (p < 0.01) better in patients with
      thrombolytic therapy compared to those with conventional therapy (13 +/- 10 vs. 3
      +/- 8%). Thus, patients without chronic preinfarction angina might benefit from
      coronary thrombolysis, while in those with preinfarction angina the beneficial
      effect of thrombolytic therapy may be relatively limited.

PMID- 8261494
TI  - Aortic dissection: diagnosis and acute-care management.

PMID- 8261495
TI  - Psychopathology in primary care patients: a four year study in rural and urban
      settings in Zimbabwe.
AB  - It has been argued that prevalence rates for psychopathology in Africa are stable
      over time and setting. There are, however, few longitudinal studies, and these
      conclusions are mainly based upon point prevalence studies. It has also been
      observed that African patients present with somatic symptoms, a feature argued to
      impede detection. Furthermore, it has been argued that such multiple somatic
      symptoms (three or more) are diagnostic of psychopathology. The present study
      examined these questions in the context of a longitudinal design. Prescriptive
      screenings of both rural and urban primary care patients were undertaken, and
      repeated the following year. The measures indicate that there is no significant
      difference in the rates in urban and rural settings, nor any difference in the
      rates over time. There were few differences between cases and non-cases in
      demographic characteristics, but there were differences in the clinical
      characteristics of the two groups. Cases tended to present with more symptoms
      than non-cases, thus corroborating earlier findings. In addition, the symptoms of
      cases tended to implicate more physiological systems than non-cases.

PMID- 8261496
TI  - The current epidemiology and control of trypanosomiasis and other zoonoses in
      Tanzania.
AB  - The epidemiology and control strategies of African trypanosomiasis, plague,
      rabies, brucellosis, anthrax and hydatidosis, the most important and well
      documented zoonotic diseases in Tanzania, have been described. Bovine
      tuberculosis, tetanus, taeniosis, trichinosis and tungosis are also endemic in
      some parts of the country but records of their incidences are not available.
      Initial outbreaks of trypanosomiasis in Tanzania were caused by Trypanosoma
      gambiense which originated from West Africa and reached Tanzania via Zaire around
      1902. T. rhodesiense which is currently responsible for human trypanosomiasis in
      Tanzania was introduced from Mozambique around 1910 and quickly spread to many
      parts of the country. The disease is currently prevalent in the western, north
      and northwestern parts, the southern highlands and southern regions. Over 6000
      cases have reported since 1979. Control strategies against sleeping sickness in
      Tanzania include chemical control of vectors, treatment of patients with
      trypanocides and avoidance of humantsetse contact. Plague is mostly endemic in
      central, northern and north-eastern Tanzania. A total of 8161 cases with 1885
      deaths have been recorded since 1890. The disease is currently prevalent in
      Lushoto district where outbreaks have been experienced since 1980, and in Singida
      district where it has been endemic since 1918. Integrated control measures are
      currently applied and were possibly responsible for the 1989 decline of outbreaks
      in the area. Financial constraints which led to deterioration of control
      activities from July 1989 probably accounted for the severe outbreaks in 1990/91
      which spread to other parts of the country. Rabies is endemic country-wide except
      in Mtwara, Lindi and Zanzibar. Domestic dogs are the principal transmitters and
      prompt vaccination and destruction of unvaccinated stray dogs are the main
      control measures. Brucellosis is widely endemic in livestock and potentially so
      in humans. Destruction of infected animals, immunisation of susceptible ones,
      proper boiling of milk and its products and chemotherapy are the currently
      applied control measures against the disease. Anthrax and hydatidosis are
      sparsely endemic in the country, and they are mostly controlled by appropriate
      meat inspection and consequent condemnation and proper disposal of the affected
      meat. Vaccination and treatment of animals are also effective against anthrax.

PMID- 8261497
TI  - Ehlers-Danlos syndrome in a Zimbabwean child.
AB  - An isolated case of Ehler-Danlos syndrome, Type 1, in a two year old Zimbabwean
      boy is described. The patient presented with failure to thrive and inability to
      stand. Examination revealed hyperextensibility of the joints and skin, umbilical
      and inguinal hernias and a perimembranous ventricular septal defect. To the best
      of our knowledge this is the first pediatric case described in the African
      literature.

PMID- 8261498
TI  - Retro-sigmoid typhoid abscess: an unusual cause of unilateral hydronephrosis in a
      child.
AB  - Salmonella infection is a major health hazard in Africa and the Third World.
      Various modes of presentation continue to come to light, which are distinctly
      unusual. Hydronephrosis from typhoid abscess is one of these unusual
      presentations never before reported. We add this to the growing list of peculiar
      complications from a very common ailment endemic in Third World environments.

PMID- 8261499
TI  - Determination of the percentage purity, active ingredients and other parameters
      in paracetamol and chloroquine syrups.
AB  - In this paper the percentage purity, active ingredients, specific gravity and the
      pH of paracetamol and chloroquine syrups were determined. For paracetamol the
      percentage purity ranged from 102.6-106.67, while the active ingredients (in mg/5
      ml base) ranged from 123.2-128. The specific gravity ranged from 1.13-1.24 and
      the pH from 4.16-5.32. For the chloroquine the percentage purity ranged from 97
      106.3, and the active ingredient 48.5-53.13, the specific gravity 1.17-1.27 and
      the pH 2.44-4.17. The results are discussed in relation to the purity, active
      ingredients and sources of the drugs. The drugs were coded. The paracetamol had a
      code of 1p-5p while the chloroquine was coded from 1c-5c.

PMID- 8261500
TI  - Alcohol problems among patients attending five primary health care clinics in
      Harare city.
AB  - Modified versions of the CAGE and WHO AUDIT (Alcohol Use Disorders Identification
      Test) questionnaires were used to investigate drinking habits of patients
      attending primary care clinics in Harare in 1989. The questionnaires were
      administered to 483 consecutive patients of whom 63 pc were male and 37 pc
      female. The results showed that 41 pc of the patients were current drinkers, and
      over 60 pc of them were drinking to and beyond "safe limits". Thirty nine pc of
      the current drinkers drank at least three or more times per week. On an average
      drinking day 66 pc of the male drinkers consume 10 or more units of alcohol per
      day. On heavy drinking days 38.5 pc of the drinkers or 16 pc of the total sample
      consume more than 21 units per day. These sessions occurred around paydays.
      Thirteen (13.2 pc) of those who consume more than 10 units per heavy drinking
      session exceeded the recommended frequency levels i.e. not more than three times
      per week. Seventy five pc of drinkers stated that they drink to socialize or for
      recreational purposes. About 60 pc of the current drinkers had tried
      unsuccessfully to cut down or stop drinking. The main reason for such an attempt
      reported by 92 pc of them was health problems. More current drinkers presented
      with STD and work-related injuries compared to non-drinkers. None of the current
      drinkers were asked about their drinking habits by the health workers who
      attended to them at the clinic. No diagnosis of alcohol dependence or an alcohol
      problem was made by the Primary Health Care worker at the clinic.

PMID- 8261501
TI  - The distribution of Schistosoma haematobium in the Isoka district, Zambia; and a
      possible strategy for its control.
AB  - The distribution of schools prevalent for Schistosoma haematobium in the Isoka
      district, Zambia was estimated by examining haematuria in the urine of the pupils
      found in Grades Three, Four or Five using reagent sticks. Thirty three (57 pc)
      schools had prevalence rates of 25 pc or more. The distribution of S. haematobium
      was patchy with significant differences in prevalence rates between some areas
      only short distances apart. A sociological study in the same schools showed that
      68 (97 pc) head/senior teachers associated the disease with blood in urine and
      agreed to perform a reagent stick test on their pupils' urine. Thirty five (50
      pc) of these respondents considered S. haematobium infection as a major problem
      and 66 (94 pc) of them were ready to administer a diagnostic questionnaire to
      their pupils in a study to identify high risk schools for S. haematobium. We
      conclude that the identification of high risk schools in the Isoka district,
      Zambia, using a diagnostic questionnaire and reagent stick testing by teachers,
      should proceed as a step to controlling S. haematobium infection in the district.

PMID- 8261502
TI  - Directory of socio-behavioural research on HIV infection and AIDS in Zimbabwe.
AB  - In July-August 1992, a directory was made of research projects on socio
      behavioural aspects of HIV infection and AIDS in Zimbabwe. A total of 92 research
      projects were identified, most of which were already completed. Whilst there was
      a wide variety of topics, populations and geographical areas covered, there was a
      strong bias towards AIDS awareness and knowledge, attitudes and practices (KAP)
      studies. Many of these were not linked with any specific AIDS prevention
      programme or with policy making. Suggestions are given to make better use of
      existing scientific information. A call is made upon researchers to conduct
      action-oriented studies and to consult HIV/AIDS programme implementers when
      specifying 'researchable' problems, so as to increase the likelihood that the
      study results will indeed have an impact on policy making and programme
      implementation.

PMID- 8261503
TI  - Thiamine-responsive acute cerebellar ataxia following febrile illness.
AB  - A case of post-pyrexial acute cerebellar ataxia in a 14 year old girl is
      presented and the available literature is reviewed. The therapeutic efficacy of
      thiamine hydrochloride observed in this patient lends some support to the view
      that acute thiamine depletion may be the pathogenetic mechanism for post-pyrexial
      acute cerebellar ataxia.

PMID- 8261504
TI  - Chronic non-strangulating incompletely obstructing intussusception: with case
      report of a seven and a half year old Nigerian boy.
AB  - One case of chronic intussusception (ileo-ileo colic) is reported. A seven and a
      half year old male had presented with colicky abdominal pain, vomiting, a
      palpable abdominal mass, infrequent passage of mucus or blood with stools and
      weight loss over a period of six weeks. There was delay in diagnosis due to
      unusual presentation and a low index of suspicion. The patient had been admitted
      to a peripheral general hospital for four weeks where he was treated for amoebic
      dysentery without improvement, before his transfer to our hospital where the
      diagnostic problem continued, until the paediatric surgical unit was called in.

PMID- 8261505
TI  - Cellular processing of beta-amyloid precursor protein and the genesis of amyloid
      beta-peptide.

PMID- 8261506
TI  - Membrane fusion takes excitatory turn: syntaxin, vesicle docking protein, or
      glutamate receptor?

PMID- 8261507
TI  - ARF signaling: a potential role for phospholipase D in membrane traffic.

PMID- 8261508
TI  - Functional reconstitution of U6 snRNA in nematode cis- and trans-splicing: U6 can
      serve as both a branch acceptor and a 5' exon.
AB  - Maturation of nuclear pre-mRNAs in nematodes requires both cis- and trans
      splicing. Both processing pathways involve analogous two-step phosphotransfer
      reactions and both are dependent upon the integrity of U6 snRNA. We have
      developed a functional reconstitution assay to assess the U6 snRNA sequence
      requirements for cis- and trans-splicing. Branch formation between the splicing
      substrates and U6 snRNA was observed. The frequency of this event was greatly
      enhanced when a highly conserved sequence in U6 snRNA was altered by mutation. In
      cis- and trans-splicing reactions reconstituted with this mutant U6 snRNA the
      liberated exon of U6 proceeded through the second step of splicing using the
      appropriate splice acceptor sites. These results demonstrate covalent
      interactions between a U snRNA required for splicing and a splicing substrate,
      and they provide evidence for an unexpected degree of catalytic flexibility
      within the spliceosome.

PMID- 8261509
TI  - Specific interactions between proteins implicated in splice site selection and
      regulated alternative splicing.
AB  - Specific recognition and pairing of the 5' and 3' splice sites are critical steps
      in pre-mRNA splicing. We report that the splicing factors SC35 and SF2/ASF
      specifically interact with both the integral U1 small nuclear ribonucleoprotein
      (snRNP U1-70K) and with the 35 kd subunit of the splicing factor U2AF (U2AF35).
      Previous studies indicated that the U1 snRNP binds specifically to the 5' splice
      site, while U2AF35-U2AF65 heterodimer binds to the 3' splice site. Together,
      these observations suggest that SC35 and other members of the SR family of
      splicing factors may function in splice site selection by acting as a bridge
      between components bound to the 5' and 3' splice sites. Interestingly, SC35,
      SF2/ASF, and U2AF35 also interact with the Drosophila splicing regulators
      Transformer (Tra) and Transformer-2 (Tra2), suggesting that protein-protein
      interactions mediated by SR proteins may also play an important role in
      regulating alternative splicing.

PMID- 8261510
TI  - Transposons in place of telomeric repeats at a Drosophila telomere.
AB  - We present the first isolation of the terminal DNA of an intact Drosophila
      telomere. It differs from those isolated from other eukaryotes by the lack of
      short tandem repeats at the terminus. The terminal 14.5 kb is composed of four
      tandem elements derived from two families of non-long terminal repeat
      retrotransposons and is subject to slow terminal loss. One of these transposon
      families, TART (telomere-associated retrotransposon), is described for the first
      time here. The other element, HeT-A, has previously been shown to transpose to
      broken chromosome ends. Our results provide key evidence that these elements also
      transpose to natural chromosome ends. We propose that the telomere-associated
      repetitive DNA is maintained by saltatory expansions, including terminal
      transpositions of specialized retrotransposons, which serve to balance terminal
      loss.

PMID- 8261511
TI  - DUN1 encodes a protein kinase that controls the DNA damage response in yeast.
AB  - DNA damage induces the expression of many genes proposed to enhance DNA repair
      capacities. We investigated the mechanism by which DNA damage induces
      transcription of RNR3, a subunit of ribonucleotide reductase. Five
      complementation groups of DNA-damage uninducible (dun) mutants were identified.
      Each is sensitive to DNA damage. dun1 mutants are also defective for RNR1 and
      RNR2 induction but are proficient for induction of other genes, defining the
      existence of at least two distinct DNA damage induction pathways. DUN1 encodes a
      nuclear protein kinase that is also a phosphoprotein. Phosphorylation of Dun1
      increases in response to DNA damage in a Dun1-dependent manner, suggesting an
      increase in autophosphorylation activity. These results establish the existence
      of a eukaryotic SOS response regulated by protein phosphorylation.

PMID- 8261512
TI  - beta-D-glucosyl-hydroxymethyluracil: a novel modified base present in the DNA of
      the parasitic protozoan T. brucei.
AB  - We have previously shown that the DNA of the unicellular eukaryote T. brucei
      contains about 0.1% of a novel modified base, called J. The presence of J
      correlates with a DNA modification associated with the silencing of telomeric
      expression sites for the variant surface antigens of trypanosomes. Here we show
      that J is 5-((beta-D-glucopyranosyloxy)-methyl)-uracil (shortened to beta-D
      glucosyl-hydroxymethyluracil), a base not previously found in DNA. We discuss
      putative pathways for the introduction of this base modification at specific
      positions in the DNA and the possible contribution of this modification to
      repression of surface antigen gene expression.

PMID- 8261513
TI  - ADP-ribosylation factor, a small GTP-dependent regulatory protein, stimulates
      phospholipase D activity.
AB  - The hydrolysis of phosphatidylcholine by phospholipase D (PLD) results in the
      production of phosphatidic acid and choline. An assay that uses an exogenous
      substrate was developed to measure this activity in membranes and solubilized
      preparations from HL60 cells. A cytosolic factor markedly enhanced PLD activity
      in membranes and was essential for GTP gamma S-dependent stimulation of an
      enriched preparation of PLD. The factor was purified to homogeneity from bovine
      brain cytosol and identified as a member of the ADP-Ribosylation Factor (ARF)
      subfamily of small G proteins. Subsequently, recombinant myristoylated ARF1 was
      found to be a better activator of PLD activity than was the nonmyristoylated
      form. ARF proteins have been implicated recently as factors for regulation of
      intracellular vesicle traffic. The current finding suggests that PLD activity
      plays a prominent role in the action of ARF and that ARF may be a key component
      in the generation of second messengers via phospholipase D.

PMID- 8261514
TI  - Tyrosine kinase-dependent suppression of a potassium channel by the G protein
      coupled m1 muscarinic acetylcholine receptor.
AB  - Neurotransmitter receptors alter membrane excitability and synaptic efficacy by
      generating intracellular signals that ultimately change the properties of ion
      channels. Through expression studies in Xenopus oocytes and mammalian cells, we
      found that the G protein-coupled m1 muscarinic acetylcholine receptor potently
      suppresses a cloned delayed rectifier K+ channel through a pathway involving
      phospholipase C activation and direct tyrosine phosphorylation of the K+ channel.
      Furthermore, analysis of neuroblastoma cells revealed that a similar tyrosine
      kinase-dependent pathway links endogenous G protein-coupled receptors to
      suppression of the native RAK channel. These results suggest a novel mechanism by
      which neurotransmitters and hormones may regulate a specific type of K+ channel
      that is widely expressed in the mammalian brain and heart.

PMID- 8261515
TI  - Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer.
AB  - Recent studies have shown that a locus responsible for hereditary nonpolyposis
      colorectal cancer (HNPCC) is on chromosome 2p and that tumors developing in these
      patients contain alterations in microsatellite sequences (RER+ phenotype). We
      have used chromosome microdissection to obtain highly polymorphic markers from
      chromosome 2p16. These and other markers were ordered in a panel of somatic cell
      hybrids and used to define a 0.8 Mb interval containing the HNPCC locus.
      Candidate genes were then mapped, and one was found to lie within the 0.8 Mb
      interval. We identified this candidate by virtue of its homology to mutS mismatch
      repair genes. cDNA clones were obtained and the sequence used to detect germline
      mutations, including those producing termination codons, in HNPCC kindreds.
      Somatic as well as germline mutations of the gene were identified in RER+ tumor
      cells. This mutS homolog is therefore likely to be responsible for HNPCC.

PMID- 8261516
TI  - Hypermutability and mismatch repair deficiency in RER+ tumor cells.
AB  - A subset of sporadic colorectal tumors and most tumors developing in hereditary
      nonpolyposis colorectal cancer patients display frequent alterations in
      microsatellite sequences. Such tumors have been thought to manifest replication
      errors (RER+), but the basis for the alterations has remained conjectural. We
      demonstrate that the mutation rate of (CA)n repeats in RER+ tumor cells is at
      least 100-fold that in RER- tumor cells and show by in vitro assay that increased
      mutability of RER+ cells is associated with a profound defect in strand-specific
      mismatch repair. This deficiency was observed with microsatellite heteroduplexes
      as well as with heteroduplexes containing single base-base mismatches and
      affected an early step in the repair pathway. Thus, a true mutator phenotype
      exists in a subset of tumor cells, the responsible defect is likely to cause
      transitions and transversions in addition to microsatellite alterations, and a
      biochemical basis for this phenotype has been identified.

PMID- 8261517
TI  - The natural history of the anterior cruciate ligament-deficient knee. A review.
AB  - The ACL-deficient knee has been a management dilemma for many years and, to this
      day, no refutable plan exists for treatment of this injury. No true prospective
      study has been performed that evaluates all types of individuals at a variety of
      activity levels, and, in this day of apparently reliable methods of
      reconstructing the ACL, it is doubtful that one will occur. The ACL injury is no
      longer a mystery to the general public; it has received extensive publicity
      because of injuries of professional athletes and the successful reconstruction in
      many of these athletes. This article has not completely cleared up the issue of
      the future of an ACL-deficient knee. It has provided, however, convincing
      evidence that an active individual with a nonfunctional ACL is susceptible to
      meniscus injury (R. Barrack, J. Bruckner, J. Kneisl, et al, personal
      communication, 1990). There is also the risk of more tears occurring with time.
      Bray and Dandy found in their follow-up of patients with ACL repairs that, if the
      pivot shift returned, these patients had a much higher incidence of meniscus
      tears. Many of these studies indicate that, if the meniscus cannot be repaired
      and requires partial meniscectomy or worse, the articular surface will
      deteriorate (R. Barrack, J. Bruckner, J. Kneisl, et al, personal communication,
      1990). Satku et al showed only 11% incidence of radiographic changes in patients
      with ACL-deficient knees with no evidence of meniscus tears compared with 100% in
      those having meniscectomy more than 5 years previously. Activity levels in
      general also change following this injury. This is probably the most difficult
      area to assess. Even though a substantial number of persons returned to their
      preinjury level of activity, it is not always possible to determine if they are
      playing with the same behavior and attitude. In other words, athletes who are
      involved in sports with cutting and jumping may modify the need for these
      activities and yet remain relatively competitive depending on their previous
      level of skill and the position they play. It has also been shown that many
      athletes return to their preinjury level initially but with time have significant
      increase in their symptoms and must modify their level of participation. More
      individuals limited their activities from the beginning than returned to their
      preinjury level (R. Barrack, J. Bruckner, J. Kneisl, et al, personal
      communication, 1990). Instability varies in these individuals and, as in Chick
      and Jackson's patients, those with mild instability (no rotatory instability) may
      do reasonably well.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8261518
TI  - Biology and biomechanics of the anterior cruciate ligament.
AB  - With detailed information concerning the role of the anterior cruciate ligament
      in the overall kinematic response of the knee during external loading, current
      clinical management of the orthopedic injuries to this joint may be improved upon
      and refined. Among the largest challenges to be met will be elucidation of the
      effects of various levels and types of muscular stabilization concurrent with a
      precise determination of the roles of passive knee restraints.

PMID- 8261519
TI  - Diagnosis for anterior cruciate ligament surgery.
AB  - We have reviewed the important aspects of the history, physical examination, and
      other diagnostic tools available to help diagnose ACL injuries. We feel that, in
      the hands of an experienced clinician, greater than 90% of ACL disruptions can be
      diagnosed at the time of injury. Appropriate evaluation will enable the clinician
      to advise the appropriate treatment, whether it be operative or nonoperative. We
      have also briefly outlined the variables that we consider to be the most
      important in the decision-making process of treatment options after ACL
      disruption.

PMID- 8261520
TI  - Role of primary anterior cruciate ligament repair with or without augmentation.
AB  - Primary ACL repair with or without extra-articular augmentation can be
      functionally and statically successful based on our experience in high
      performance athletes. Proper surgical technique, appropriate rehabilitation, and
      excellent quality of the tissue being repaired are required to achieve these
      results. Several notable improvements in diagnostic imaging, physical
      examination, surgical technique, and rehabilitation protocol have led to
      excellent results. The notchplasty, multiple loop suture technique, and improved
      meniscal repair are key factors. Moreover, we believe that one of the prime
      enhancements is to provide the highly stable extra-articular lateral capsular
      ligament reconstruction described previously. Laboratory findings have shown that
      this procedure provides excellent support against anterior subluxation
      immediately after surgery. It appears that release of the iliotibial band tissue
      proximally prevents stretching and failure of this extra-articular procedure.
      Rehabilitation unquestionably is a critical factor in the success of this
      surgical procedure. Immediate motion and appropriate biomechanical stresses on
      the repaired ligament have proved compatible with good functional and objective
      results. Even though intra-articular reconstruction of the torn ACL continues to
      be considered the gold standard, we remain convinced that primary repair of the
      ACL with appropriate extra-articular augmentation should not be ruled out in many
      cases. This procedure clearly is a viable, successful, and acceptable alternative
      to intra-articular reconstruction in selected cases.

PMID- 8261521
TI  - The role of osteotomy in the anterior cruciate ligament-deficient knee.
AB  - Whether the ACL-deficient knee actually causes osteoarthritis is unclear. What is
      clear is that the two conditions can exist simultaneously. Treatment of these
      patients must be individualized based on their activities, symptoms, and
      findings. In the unusual patient with significant instability and moderate medial
      compartment osteoarthritis, a combined valgus osteotomy and ACL reconstruction
      may be appropriate. The authors emphasize that this is a salvage procedure, not
      intended to return the athlete to competition. Although the short-term results
      are promising, the long-term results of this treatment are unknown.

PMID- 8261522
TI  - Anterior cruciate ligament reconstruction: long-term results using autograft
      tissue.
AB  - Injuries involving the anterior cruciate ligament are quite common. Numerous
      surgical procedures have been proposed for the management of the symptomatic ACL
      deficient knee. The most popular treatment modality is currently intra-articular
      reconstruction with the use of autogenous graft tissue. The focus of this article
      is to review the long-term results of autograft ACL reconstruction.

PMID- 8261523
TI  - The use of hamstring tendons for anterior cruciate ligament reconstruction.
      Technique and results.
AB  - We feel that some of the current prejudice against use of hamstring tendon grafts
      for ACL reconstruction has not been justified if one critically reviews the
      literature. In this article, we have tried to provide the reader with our current
      indications, present our current surgical technique, and review some of the
      outcome studies involving use of the hamstring tendons for ACL reconstruction. We
      also feel that some of the poor results of hamstring tendon ACL reconstructions
      previously reported resulted from the use of inadequate strength grafts (single
      stranded grafts) and lack of rigid fixation on both ends of the graft (usually
      secondary to inadequate graft length). We feel that the technique described in
      this article addresses both of these issues. It is our clinical impression that,
      in appropriately selected patients, this technique produces stability and
      functional outcome similar to that obtained with patellar tendon grafts but
      results in less postoperative pain, a quicker return of quadriceps muscle
      function, and less donor site morbidity.

PMID- 8261524
TI  - The use of allograft. Techniques and results.
AB  - There are several advantages to allograft use for ACL reconstruction. Bone
      patella, tendon-bone, and achilles tendon allografts are routinely used. The one
      incision endoscopic technique is described. Very few comparative studies exist in
      the current literature, but clinical results with allograft tissues appear to be
      similar to those of autograft use.

PMID- 8261525
TI  - The meniscus in the cruciate-deficient knee.
AB  - Evidence clearly implicates meniscectomy as a primary factor in the premature
      development of OA of the knee joint. Although data demonstrate the ability of the
      menisci to transmit load, they do not contribute to the primary stability of the
      knee. In the absence of the ACL, the menisci have been shown to enhance the
      knee's stability in the AP, varus-valgus, and internal-external directions in
      vitro. Clinically, the argument that the menisci are important secondary
      stabilizers is less clear. The restraining capacity of the menisci to AP
      translation is much smaller than the forces the knee is subjected to in vivo
      during activities of daily living. Additionally, these forces can increase as
      much as threefold during strenuous athletics. It becomes apparent, on review of
      the literature, that the menisci clearly are not designed to participate as a
      significant restraining mechanism for the ACL-deficient knee. The incidence of
      acute meniscal tear is 52% and increases to 83% in the long run. It is important
      to realize that although the menisci contribute in part to the stability of the
      ACL-deficient knee, such a role places them at risk for injury. When meniscal
      lesions are noted in the ACL-deficient knee, it is important to bear in mind the
      patient's goals, including his or her willingness to have an ACL reconstructive
      procedure and desire to return to sports. Also, the tear's configuration and
      location dictate its the ability to heal. One final area of interest relates to
      the fate of an ACL reconstruction in the meniscus-deficient knee. Although the
      meniscus is not a participant in primary stability, the subtle alteration in knee
      joint kinematics may create unfavorable conditions for the ACL graft. It is
      possible that the menisci may provide some protection to an ACL-reconstructed
      knee by restoring normal knee joint kinematics. Such a situation may explain why
      some ACL reconstructions in the meniscectomized knee fail over time. Prosthetic
      meniscal substitution or allograft meniscal transplantation are techniques on the
      horizon and may prove useful in the future when the remaining meniscus cannot be
      repaired.

PMID- 8261526
TI  - Modern trends in anterior cruciate ligament rehabilitation: nonoperative and
      postoperative management.
AB  - Rehabilitation following ACL injury or reconstruction should be based on sound
      scientific and rehabilitation principles. Basic science principles related to
      rehabilitation following ACL injury and reconstruction have been reviewed.
      Guidelines incorporating these basic science principles as well as clinical
      experience were presented for rehabilitation following ACL injury and
      reconstruction.

PMID- 8261527
TI  - Role of extra-articular procedure.
AB  - This article describes the 1993 role of extra-articular procedures in the
      treatment of anterior cruciate-deficient knees. Twenty years ago, most operative
      effort was concentrated on elimination of the pivot shift phenomenon. Newer
      operative reconstructions made most of the advantages attributed to
      extraarticular procedures (shorter operating room time, less soft tissue injury,
      shorter postoperative rehabilitation) no longer true.

PMID- 8261528
TI  - The anterior cruciate ligament in the multiple ligament-injured knee.
AB  - The ACL may be associated with concomitant injury to the posterior cruciate
      ligament, collateral structures, bone or cartilage. An approach to the
      multiligament injured knee is discussed including evaluation, treatment, graft
      selection, operative techniques, graft placement, tensioning, fixation,
      impingement, postoperative care, and complications.

PMID- 8261529
TI  - Revision anterior cruciate ligament surgery: causes of graft failure and
      technical considerations of revision surgery.
AB  - The frequency of revision ACL surgery is sure to become more common as the number
      of primary intraarticular reconstructions increase. Identifying the potential
      causes of failure through a detailed history, physical examination, and
      radiographic evaluation is of paramount importance prior to planning a revision
      surgery if the repetition of errors is to be avoided.

PMID- 8261530
TI  - Can melatonin improve shift workers' tolerance of the night shift? Some
      preliminary findings.
AB  - The pineal hormone melatonin is potentially useful in the treatment of disorders,
      especially sleep disorders, associated with circadian rhythm disturbance. We have
      examined its effects on sleep, mood, and behaviour in a double-blind, placebo
      controlled study of a small group of police officers working spans of seven
      successive night shifts. Compared to placebo, and to no treatment, melatonin (5
      mg) taken at the desired bedtime improved problems related to sleep and increased
      alertness during working hours, especially during the early morning. In letter
      target performance tests visual search speed and accuracy were either unchanged
      or slightly improved. Memory scanning speed and perception of mental load were
      adversely affected. This preliminary study suggests that melatonin has beneficial
      effects on sleep and alertness, but that its effects on performance need careful
      evaluation.

PMID- 8261531
TI  - The effects of lithium on a neuronal in vitro circadian pacemaker.
AB  - Previous studies have suggested a causal connection between abnormalities of the
      circadian system and affective disorders. The effectiveness of lithium or
      rubidium as a treatment for affective disorders and the ability of lithium or
      rubidium to influence circadian pacemakers has stimulated research into the
      mechanism of lithium's action on circadian systems. In this study we used a
      neuronal in vitro circadian pacemaker preparation, the eye of the mollusc Bulla,
      to examine the cellular effects of lithium and rubidium. Continuous extracellular
      LiCl application lengthens the period of the circadian rhythm of the Bulla
      pacemaker in a concentration-dependent manner. Rubidium was found to be more
      effective than lithium in period lengthening. Stable phase delays were generated
      by 2-h pulses of 395 mM LiCl applied extracellularly from zeitgeber time (ZT) 5-7
      (mid subjective day). Concomitant continuous application of 16 mM LiCl and light
      (a depolarizing agent) generated period lengthening substantially greater than
      the arithmetic sum of the modest period lengthening of each treatment alone.
      Furthermore, LiCl pulses, applied together with depolarizing extracellular KCl
      concentrations, yielded an increasing magnitude of phase delays with increasing
      KCl concentration. These data suggest that LiCl acts intracellularly on the
      circadian pacemaker cells by entering through a voltage-dependent channel, most
      likely a sodium channel.

PMID- 8261532
TI  - Chronobiologic evaluation of angiotensin-converting enzyme activity in serum and
      lung tissue from normotensive and spontaneously hypertensive rats.
AB  - Angiotensin-converting enzyme (ACE) activity in serum and lung tissue from both
      normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was
      determined at six different circadian times. In WKY rats serum ACE varied
      significantly within 24 h, mainly due to reduced enzyme activity at 12:00 h. In
      SHR the 24-h profile of serum ACE did not exhibit time-dependent differences.
      Mean serum ACE activity over 24 h was significantly higher in WKY than in SHR. In
      lung tissue ACE activity did not depend on the circadian time in either strain.
      Mean enzyme activity in lung tissue was not different between WKY and SHR. We
      conclude that circadian changes in the activity of serum and tissue ACE are
      unlikely to play an important role in the regulation of the circadian blood
      pressure profile in both normotensive and spontaneously hypertensive rats.

PMID- 8261533
TI  - Influence of feeding schedule on chronopharmacological aspects of gentamicin in
      mice.
AB  - The effects of the time of day of drug administration on the subchronic toxicity
      and pharmacokinetics of gentamicin, as well as the role of feeding schedule on
      circadian rhythms, were investigated in mice. ICR male mice were housed in a
      light-dark (LD) cycle (12:12) with food and water ad libitum (ALF) or under a
      time-restricted feeding (TRF) schedule (feeding time: 8 h during the light phase)
      for 1 day or 14 days before drug administration. The animals were given a single
      subcutaneous dose of gentamicin 180 mg/kg for the kinetic studies and
      subcutaneous doses of gentamicin 180 mg/kg/day for 14 days or 220 mg/kg/day for
      18 days for the subchronic toxicity studies. A significant dosing-time dependency
      was shown for mortality and body weight loss, with higher values at midlight and
      lower ones at the middark (p < 0.05). A significant circadian rhythm was also
      found for gentamicin kinetics in ALF mice, with the highest clearance at middark
      and the lowest one at midlight (p < 0.01). The kinetic rhythm of gentamicin
      coincided well with the toxicity rhythm of the drug. The TRF schedule had a
      marked influence on the rhythms of gentamicin kinetics and toxicity, showing
      lowest clearance and higher toxicity at middark. The rhythm of subchronic
      toxicity of gentamicin seems to be due, at least in part, to the rhythm in
      kinetics and is strongly influenced by the feeding schedule. Thus, the timing of
      dosing is an important factor in the kinetics and the subchronic toxicity of
      gentamicin administration in mice, and the manipulation of feeding schedule can
      modify the rhythm of the toxicity by changing the rhythm of gentamicin kinetics.

PMID- 8261534
TI  - Circadian variations in the number of actively secreting sebaceous follicles and
      androgen circadian rhythms.
AB  - Sebum excretion has been shown to demonstrate a circadian rhythm using a
      gravimetric method (cigarette paper). With the newly introduced method of
      Sebutape, we confirmed this periodicity and showed that the elevation in sebum
      excretion is correlated with an increase in the number of secreting follicles. We
      found, furthermore, that the number of secreting follicles on the forehead showed
      a distinct and statistically significant circadian rhythmicity, in contrast to
      those of the chest, which remained almost constant. The quantification in plasma
      levels of cortisol, melatonin, delta-4-androstenedione, dehydroepiandrosterone
      sulphate, and free testosterone showed no correlation with sebum excretion at
      either site. These observations suggest that local factors are involved in
      control of sebum secretion.

PMID- 8261535
TI  - Circannual variations of the bleeding time in the rat.
AB  - This study was carried out to determine the annual fluctuations of the tail
      bleeding time in the rat. Bleeding time was determined by transection of the tail
      of pentobarbital-anesthetized rats. Over a 6-year period, monthly measurement of
      the tail bleeding time revealed highly reproducible circannual fluctuations.
      Bleeding times were shortened in the summer (414 +/- 18 s in July), being almost
      half that observed during the winter span (886 +/- 32 s in January). The
      difference between these two time points was highly significant (p < 0.001). This
      study reports for the first time circannual variations of the bleeding time in
      the rat.

PMID- 8261536
TI  - Circannual variations in baseline blood values of dogs.
AB  - Forty-two hematological and biochemical variables routinely measured in dogs as
      part of a preoperative protocol have been analyzed for circannual changes by
      analysis of variance (ANOVA) and single cosinor procedures. Data were available
      from up to 489 adult mongrel dogs of both sexes studied on weekdays over a 5-year
      span (January 5, 1987 to December 18, 1991). Dogs were housed in individual cages
      at 24 +/- 1 degrees C with dog chow and tap water available ad libitum and lights
      on between 06:00 and 18:00 h. A single blood sample/dog was collected by jugular
      venipuncture between 08:00 and 09:00 h and sent to a commercial laboratory for
      hematological and biochemical determinations. Data were assigned to date and time
      of sampling and analyzed for the effect of time of year by ANOVA (across 12
      months and 4 seasons), and by the least-squares fit of a precise 1-year cosine.
      ANOVA and single cosinor described a significant circannual time effect and
      rhythm for the following: total leukocytes, lymphocytes, hemoglobin, mean
      corpuscular hemoglobin (MCH), MCH concentration, red cell distribution width,
      mean platelet volume, creatinine, blood urea nitrogen (BUN), BUN/creatinine
      ratio, amylase, glucose, chloride, uric acid, direct bilirubin, total protein,
      albumin, globulin, albumin/globulin ratio, lactate dehydrogenase, alkaline
      phosphatase, gamma-glutamyltransferase, alanine aminotransferase (ALT), and
      aspartate aminotransferase (AST)/ALT ratio. A significant effect of season by
      ANOVA only was found for: Ca, Na, phosphorus, total bilirubin, hematocrit, mean
      corpuscular volume, and neutrophils. No significant time effect could be found at
      p < or = 0.05 by either statistical method for: K, Mg, Fe, cholesterol,
      triglycerides, ASP, red blood cells, monocytes, eosinophils, basophils, or
      platelets. Acrophases occurred for the most part in either the winter or summer.

PMID- 8261537
TI  - Evidence for genetic basis of seasonal differences in antibody formation between
      two mouse strains.
AB  - In order to confirm the presence of an acrophase difference based upon genotype
      in the seasonal expression of an immune competence end point, splenic plaque
      forming cell (PFC) response to sheep red blood cells (SRBC), female B6C3F1 and
      CD1 mice were concurrently studied for PFC response during two studies performed
      in each season for 1 year. Mice were multiply housed, fed ad libitum, and
      standardized to light (06:00-18:00); dark (18:00-06:00). For each strain and
      study, subgroups were either naive (n = 10), received a vehicle (n = 10) or
      Cytoxan (n = 5). Challenge with SRBC occurred in early afternoon 4 days before
      harvesting of spleens and PFC assay. All other procedures were performed early in
      the daily light span. Analysis of variance and single cosinor analysis revealed a
      significant seasonal time effect for PFC in naive mice of both strains. Antibody
      formation was greatest in spring for CD1 mice and in summer for the B6C3F1 mice.
      These acrophases were consistent with earlier results for both strains and show
      the phenomena to be reproducible and genetically based.

PMID- 8261538
TI  - Sightseeing around the single cosinor.
AB  - Misuses of the single cosinor analysis are numerous. We give three rules of
      thumb, providing guidelines as to whether results obtained from this analysis are
      dubious. This short note avoids mathematical development so as to be
      comprehensible to the nonspecialist. However, a few endnotes, give some technical
      comments.

PMID- 8261539
TI  - Wound care: moving to new concepts within an old theme.

PMID- 8261540
TI  - Student nurses' perception of the clinical midwifery experience as a learning
      environment.
AB  - The student nurse may have a different perception of her learning environment
      from that which the instructor intended. The purpose of the study was to
      determine the perception of student nurses of clinical midwifery experience as a
      learning milieu. Student nurses in their third and fourth year at a nursing
      college in Transvaal were involved in the research. A literature study regarding
      factors that can influence clinical learning of student nurses in the midwifery
      units was done. Questionnaires were used to collect data regarding personal
      information, the learning environment, and problems regarding clinical skills.
      Data were analysed by means of a SAS computer programme. Certain problem areas,
      for example the need for clinical lecturers to attend units on a more regular
      basis, as well as the more negative attitude of fourth year respondents compared
      to third years, were indicated. The necessary recommendations were made and
      reported to the nursing college concerned.

PMID- 8261541
TI  - Policy-making for real: politics and progress in South African health care.

PMID- 8261543
TI  - The professional educational needs of non-practising nurses registered with the
      South African Nursing Council.

PMID- 8261542
TI  - [The nurse as preceptor in personnel development in teaching hospitals in
      Namibia].
AB  - A study undertaken in 1991 focused on the role fulfilment of the preceptor in
      staff development in training hospitals in Namibia. As in the case in many
      countries the nursing service climate in Namibia is characterised by constant
      change in the practice of professional nurses. The preceptor must accompany the
      professional nurses in their personal and professional development.

PMID- 8261544
TI  - [A model for psychiatric nursing accompaniment of a patient with mental
      discomfort: Part II].
AB  - The conceptualization of the concept mental discomfort formed only part of the
      research methodology. The goal was to conceptualize the concept mental discomfort
      in the conceptual frame of reference of Psychiatric Nursing. The concept was one
      of three concepts to be analyzed in this research. The combined approach of
      concept analysis was used. This was done as follows: Research dictionary and
      subject terminological definitions of the concept; Construct cases of the
      concept: a model and borderline case; Formulate criteria for the concept; Conduct
      internal dialogue; Reformulate and define the concept. After completion of the
      process the concept mental discomfort was conceptually defined.

PMID- 8261545
TI  - An adaptation of the Neuman Systems Model to the care of the hospitalized
      preschool child.
AB  - This article describes an adaptation of the Neuman Systems Model to the care of
      the hospitalized preschool child. This was done to unite the physical care of the
      hospitalized preschool child with other aspects of his development and to
      describe the causes and prevention of stresses of hospitalization for this child.

PMID- 8261546
TI  - [The experiences of parents with an ill premature baby].
AB  - The purpose of this study was to identify and describe the experience of the
      parents of an ill premature infant in order to identify the needs of the parents
      going through this potential crisis. As a result of the constant medical and
      technological progress the percentage of premature infants is continually
      increasing. It is therefore of vital importance that the nursing and other
      medical staff are made aware of the trauma that these parents experience. This
      will enable them in giving adequate support and accompaniment in the prevention
      of social pathology. Unstructured in-depth interviews were held with five couples
      on two occasions. The first interview was held shortly after the birth of the
      premature infant. The second interview was held approximately two weeks after the
      baby was discharged from a private hospital in the Johannesburg region. The
      emotions of the parents were identified and compared. A literature study was done
      to consult other authors' findings on this topic. Recommendations were made at
      the end of the study concerning applications to practise, education and further
      research needed.

PMID- 8261547
TI  - Critical evaluation of the newly qualified nurse's competency to practise--Part
      1.
AB  - The competence of the newly qualified nurse practitioner is questioned. Critical
      evaluation of the competency of the newly qualified nurse is performed by means
      of self evaluation as well as evaluation by the newly qualified nurse's
      supervisor. This study shows the relationship between competency of the newly
      qualified nurse and placement, orientation and guidance. Data analysis indicated
      that there is no significant relationship between the competency of the newly
      qualified nurse and placement and orientation. The importance of adequate
      guidance to the newly qualified nurse was quite clear.

PMID- 8261548
TI  - Critical evaluation of the newly qualified nurse's competency to practice--Part
      2.

PMID- 8261549
TI  - [Comparison between nursing in child psychiatry in South Africa and in San
      Francisco].
AB  - The provision of services to children with psychiatric disorders in the Republic
      of South Africa--especially black and underprivileged children--is limited and
      inadequate. The practice of the nurse in the field of child psychiatry is vague
      and undeveloped and there are few nurses in South Africa with the knowledge and
      skills to set guidelines for this area of practice. A qualitative field study was
      undertaken in South Africa and San Francisco to analyze, describe and compare the
      situation in regard to contemporary nursing practice in child psychiatry. The
      result showed that nurses in San Francisco were academically better qualified
      than their colleagues in South Africa, while many similarities regarding
      therapeutic skills were found. Problems in South Africa included rigid systems,
      insufficient recognition, poor job descriptions and inadequate supervision. Large
      numbers of nurses who are specialized in child psychiatry have left the health
      services as a result of frustration and problems encountered in practice. These
      problems must be addressed in order to retain nurses recruited to this field of
      practice.

PMID- 8261550
TI  - Academic nurse leaders' interpretation of concepts and priorities related to the
      examination of scientific short papers, dissertations and theses--Part 1.
AB  - The purpose of this study was to establish whether there is agreement among
      academic nurse leaders in their interpretation of aspects and criteria related to
      the examination of scientific short papers, dissertations and theses. The Delphi
      technique was selected as the most appropriate method of data-collection for this
      type of study. The target population identified for this study consisted of the
      Heads of Nursing Departments or their delegates from the 18 universities of the
      four provinces of the RSA, self-governing and independent states of Southern
      Africa and Namibia, which offer nursing degrees. Three rounds of questionnaires
      were sent to all heads of the 18 identified nursing departments. Participation
      was poor (nine participated in first round, nine in second the third round, no
      further rounds of questionnaires were sent due to the waning interest and poor
      participation. Many divergent responses were received to most of the aspects
      included in the study. This indicates that with a few exceptions there is little
      or no agreement among academic nurse leaders in their interpretation of aspects
      and criteria relating to the examination of post-graduate scientific or academic
      treatises.

PMID- 8261551
TI  - [Botes' article: A model for qualitative research in nursing. Curationis:
      December 1992].

PMID- 8261552
TI  - Childhood blindness: a new form for recording causes of visual loss in children.
AB  - The new standardized form for recording the causes of visual loss in children is
      accompanied by coding instructions and by a database for statistical analysis.
      The aim is to record the causes of childhood visual loss, with an emphasis on
      preventable and treatable causes, so that appropriate control measures can be
      planned. With this standardized methodology, it will be possible to monitor the
      changing patterns of childhood blindness over a period of time in response to
      changes in health care services, specific interventions, and socioeconomic
      development.

PMID- 8261553
TI  - Maintenance and distribution of transgenic mice susceptible to human viruses:
      memorandum from a WHO meeting.
AB  - This Memorandum discusses the use of transgenic mice in poliovirus research and
      the potential risks to public health. General and specific recommendations are
      given concerning the maintenance, containment and transport of transgenic animals
      which are susceptible to pathogenic human viruses, with special attention to
      transgenic mice susceptible to polioviruses.

PMID- 8261554
TI  - 1993 guidelines for the management of mild hypertension: memorandum from a
      WHO/ISH meeting.
AB  - The present guidelines were prepared by the Guidelines Sub-Committee of the
      WHO/ISH (International Society of Hypertension) Mild Hypertension Liaison
      Committee. They represent the third revision of the WHO/ISH guidelines and were
      finalized after discussions at the Sixth WHO/ISH Meeting on Mild Hypertension in
      Chantilly, France, on 28-31 March 1993. The new guidelines discuss the
      cardiovascular risk in patients with hypertension, the definition and
      classification of mild hypertension, drug treatment (including the elderly) and
      non-drug measures, cost-effectiveness, and further research.

PMID- 8261555
TI  - Assessment of respiratory rate and chest indrawing in children with ARI by
      primary care physicians in Egypt.
AB  - In a baseline study for training purposes, two indicators of acute respiratory
      infections (the respiratory rate (RR) and chest indrawing) were assessed by
      Ministry of Health physicians in Egypt using a WHO test videotape. Chest
      indrawing, as defined by the WHO Acute Respiratory Infections (ARI) programme,
      was not widely recognized by current health personnel. Viewing a WHO training
      videotape led to significantly more correct assessments of chest indrawing
      compared with a group that had not viewed this videotape. The accuracy of using a
      timer versus a watch, and a 30-second versus 60-second counting interval was also
      evaluated. Rates counted over 60 seconds were more accurate than 30-second counts
      although the difference between them was not clinically significant. Counting of
      rates using timers with audible cues was comparable to using watches with second
      hands. Careful training of primary health workers in the assessment of RR and
      chest indrawing is essential if these clinical findings are to be used as
      reliable indicators in pneumonia treatment algorithms.

PMID- 8261556
TI  - Motherhood and infant health in Khartoum.
AB  - The results of an analysis of the growth and illness experience of a group of
      infants in Khartoum townships illustrate the remarkable benefits of being the
      infant of a "housewife" rather than the infant of a mother who works. These
      benefits occurred despite the poorer domestic environments of the housewives.

PMID- 8261557
TI  - Evaluation of the home-based maternal record: a WHO collaborative study.
AB  - Thirteen centres in eight countries (Egypt, India, Pakistan, Philippines,
      Senegal, Sri Lanka, Democratic Yemen and Zambia) participated in the WHO
      collaborative study to evaluate the home-based maternal record (HBMR). The
      evaluation showed that use of the HBMR had a favourable impact on utilization of
      health care services and continuity of the health care of women during their
      reproductive period. When adapted to local risk conditions, their cut-off points
      and the available resources, the HBMR succeeded in promoting self-care by mothers
      and their families and in enhancing the timely identification of at-risk cases
      that needed referral and special care. The introduction of the HBMR increased the
      diagnosis and referral of at-risk pregnant women and newborn infants, improved
      family planning and health education, led to an increase in tetanus toxoid
      immunization, and provided a means of collecting health information in the
      community. The HBMR was liked by mothers, community health workers and other
      health care personnel because, by using it, the mothers became more involved in
      looking after their own health and that of their babies. Apart from local
      adaptation of the HBMR, the training and involvement of health personnel
      (including those at the second and tertiary levels) from the start of the HBMR
      scheme influenced its success in promoting maternal and child health care. It
      also improved the collection of community-based data and the linking of referral
      networks.

PMID- 8261558
TI  - Studies of missed opportunities for immunization in developing and industrialized
      countries.
AB  - Missed opportunities for immunization are an obstacle to raising immunization
      coverage among children and women of childbearing age. To determine their global
      magnitude and reasons, studies reported up to July 1991 were reviewed. A standard
      measure for the prevalence of missed opportunities was calculated for each study.
      Seventy-nine studies were identified from 45 countries; 18 were population-based,
      52 were health-service-based, and 9 were intervention trials. A median of 32%
      (range, 0-99%) of the children and women of childbearing age who were surveyed
      had missed opportunities during visits to the health services for immunization or
      other reasons. Missed opportunities were mainly due to failure to administer
      simultaneously all vaccines for which a child was eligible; false
      contraindications; health workers' practices, including not opening a multidose
      vaccine vial for a small number of persons to avoid vaccine wastage; and
      logistical problems. To eliminate missed opportunities for immunization,
      programmes should emphasize routine supervision and periodic in-service training
      of health workers which would ensure simultaneous immunizations, reinforce
      information about true contraindications, and improve health workers' practices.

PMID- 8261559
TI  - The reasons for early weaning among mothers in Teheran.
AB  - In order to identify the reasons for early weaning in Teheran, we interviewed 900
      mothers using a systematic randomized sampling method. A total of 15% of the
      mothers were illiterate, 93% were housewives, and 97% had given birth in
      hospitals. Only 3% of the newborns benefited from rooming-in facilities in
      hospital, and 68% were bottle-fed while still in hospital. In 3.1% of cases the
      mother had not breast-fed her newborn at all. Of those who had breast-fed their
      infant, 38% used only their own milk, whereas 62% used a combination of breast
      milk and infant formula. The median duration of breast-feeding was 16 months
      (mean, 14 months). A total of 74% of mothers who used supplementary formula and
      39% of those who had completely stopped breast-feeding blamed milk insufficiency,
      although 67% of these mothers had reached this conclusion only because their
      infants cried or were irritable. The following factors had a negative influence
      on the duration of breast-feeding: use of supplementary formula and of estrogen
      containing oral contraceptives; fathers with high incomes; and mothers with a
      high educational level. In contrast, the mother's religious motive to breast-feed
      and her insistence on breast-feeding had a positive impact. Unfortunately, 21% of
      the mothers started using supplementary formula during the first month
      postpartum, and two-thirds before the end of the fourth month. Every month that
      bottle-feeding was started prematurely shortened the duration of breast-feeding
      by 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261560
TI  - Initiation of food supplements and stopping of breast-feeding as determinants of
      weanling shigellosis.
AB  - The association between the period elapsed since weaning and the risk of
      shigellosis was assessed between 1 November 1987 and 30 November 1989 for a
      cohort of 1085 Bangladeshi children aged < 3 years. The children were followed
      for 1 month after exposure to Shigella spp. in their residential neighbourhoods,
      and the 268 who developed microbiologically confirmed (n = 118) or clinically
      presumptive (n = 150) shigellosis were compared with the 817 control children who
      did not develop either syndrome. No increase in risk was noted among breast-fed
      infants who received food supplements within the previous 3 months compared with
      those who had received supplements for longer (adjusted odds ratio (OR) = 1.2;
      95% confidence interval (CI) = 0.4-3.0). However, compared with breast-fed
      children, non-breast-fed children had an increased risk (adjusted OR = 2.0; 95%
      CI = 1.3-2.9; P < 0.001), which was largely attributable to a substantially
      increased risk in the 3 months after stopping breast-feeding (adjusted OR = 6.6;
      95% CI = 2.9-14.6; P < 0.001). The early post-cessation risk was equivalent for
      confirmed and presumptive shigellosis, but was particularly pronounced among the
      severely malnourished (adjusted OR = 10.2; 95% CI = 3.1-33.3; P < 0.001). This
      complex temporal pattern of risk highlights the need for precise definitions of
      weaning to facilitate identification of children at high risk for invasive
      diarrhoeal syndromes.

PMID- 8261561
TI  - Costs of diarrhoeal diseases and the savings from a control programme in Cebu,
      Philippines.
AB  - A control of diarrhoeal diseases programme was set up in Cebu Province,
      Philippines, in 1986. In order to compare the reduction in treatment costs before
      and after implementation of the programme, and the potential savings to be made
      from its continuation, we collected data for 1985 and 1989 in 10 health
      facilities in Cebu. Since the programme's introduction, household expenditures on
      drugs for diarrhoea cases have decreased by a total of 1.03 million Philippine
      pesos (P) (US$ 41,200). At the health centre level, the costs of treating
      diarrhoea cases were close to optimum, but in the district hospitals treatment of
      inpatients with diarrhoea changed little between 1985 and 1989. This arose
      because such hospitals were compensated by the central authorities for inpatients
      but not for outpatients. Potential savings of around US$ 60,000 could have been
      made, however, had the district hospitals adopted the practices used in the main
      referral hospital.

PMID- 8261562
TI  - [To screen or systematically treat a population at risk? A method based on the
      analysis of costs applicable at the level of district health].
AB  - With severely limited resources, it is necessary for the health services to
      select the most efficient strategy for managing health problems in a population
      at risk. A simple method for cost analysis, which can be used at the district
      health care level, is proposed so that one can choose between selective treatment
      on the basis of case identification, or indiscriminate treatment of the entire
      population at risk. The treatment of anaemia at the antenatal clinic in health
      centres in southwestern Chad was studied and is presented as an example. The
      conditions for use and the limitations of the method are discussed.

PMID- 8261563
TI  - The costs of HIV prevention strategies in developing countries.
AB  - Since many evaluations of HIV (human immunodeficiency virus) prevention
      programmes do not include data on costs, a preliminary analysis of the costs and
      outputs of a sample of HIV prevention projects was attempted. Case studies,
      representing six broad HIV prevention strategies in developing countries with
      differing levels of per capita gross domestic product, were sought on the basis
      of availability of data and potential generalizability. The six prevention
      strategies studied were mass media campaigns, peer education programmes, sexually
      transmitted disease treatment, condom social marketing, safe blood provision, and
      needle exchange/bleach provision programmes. Financial cost data were abstracted
      from published studies or were obtained directly from project coordinators.
      Although estimates of cost-effectiveness were not made, calculations of the
      relative cost per common process measure of output were compared. Condom
      distribution costs ranged from US$ 0.02 to 0.70 per condom distributed, and costs
      of strategies involving personal educational input ranged from US$ 0.15 to 12.59
      per contact.

PMID- 8261564
TI  - [An epidemiological survey to discover the probable places of infection with
      sleeping sickness in the Central African Republic].
AB  - The sleeping sickness focus at Nola-Bilolo in the forest region was the subject
      of a survey of 142 patients in order to discover their probable places of
      infection. Seventy of these patients had been detected by active case-finding
      during a survey conducted in January-February 1991; the other 12 had been
      discovered by passive case-finding during 1990. The sample of actively detected
      patients is significantly younger (average 22 +/- 3 years) than the sample
      detected passively (30 +/- 3 years). This survey highlights the geographical
      heterogeneity of transmission in the focus. The places where infection is highest
      are M'Poyo, which with 18% of cases forms the epicentre of the focus and the main
      reservoir of infecting flies, followed by Bilolo (9%), Mekara (8%), Modigui
      Kouna, Ziendi and Domissili (7%). The patients, 95% of whom belong to the M'Bimou
      tribe, all engage in agriculture; the main activities are coffee-growing for men
      and the steeping of casava in the river for women. These two activities determine
      the main places and times of human-tsetse contact. The information obtained by
      listing the cases detected passively from medical registers is inadequate for
      locating the places of transmission. The information gathered during active case
      finding campaigns by the mobile teams offers a better approach. The method used
      here, which is recommended, consists of matching the replies given by the
      patients about their points of contact with the tsetse flies, not just with their
      places of residence but also with their successive movements and their places of
      work. The rigour demanded by this kind of approach can only be ensured by a
      specific survey. This survey also made it possible to demonstrate substantial
      movements from village to village, which appear to be characteristic of this
      focus. The results indicate that poorly targeted vector control is likely to be
      doomed to failure. The study makes it possible to specify priority areas for
      vector control by trapping and to avoid a "blind" control strategy whereby the
      whole focus is swamped with traps. The latter strategy is not financially
      feasible for many countries of tropical Africa.

PMID- 8261566
TI  - Occupational exposure of Sri Lankan tea plantation workers to paraquat.
AB  - Absorption of the herbicide paraquat (1,1'-dimethyl-4,4'-bipyridinium) by mixer
      loaders and spray operators on a Sri Lankan tea plantation was assessed over five
      consecutive days of spraying. Beginning on the day before spraying started and
      continuing for each of the five spraying days and for seven days after the last
      day of spraying, 24-hour urine samples were collected from each of the workers.
      Potential dermal exposure was assessed during further applications of paraquat on
      the day after the last day of urine collection. For this purpose two spraying
      replicates were conducted that involved the handling or spraying of an amount of
      paraquat equivalent to the maximum used per day in the assessment of absorption.
      The mixer-loaders and spray operators incurred, on average, approximately
      equivalent amounts of potential dermal exposure (66 mg and 74 mg paraquat ion,
      resp.); however, the distribution of the exposure differed. About 86% of the
      total exposure experienced by the mixer-loaders was to the hands, whereas about
      90% of the exposure of the spray operators involved their hands, legs, and feet,
      in approximately equal proportions. In both cases, 90% or more of the total
      potential exposure involved parts of the body that were normally uncovered.
      Despite the evidence of dermal exposure, no paraquat was detected in the workers'
      urine. This probably was due to the very low concentration of paraquat in the
      solutions used for spot spraying on tea plantations (0.3-0.4 g paraquat ion per
      litre), the high standard of personal hygiene exercised by the workers, and the
      low permeability of human skin to paraquat.

PMID- 8261565
TI  - Urban epizootic of rabies in Mexico: epidemiology and impact of animal bite
      injuries.
AB  - From 1 July 1987 to 31 December 1988, a total of 317 animals (91% of which were
      dogs) were confirmed to have rabies in Hermosillo, Mexico. The median age of
      rabid dogs was 1 year, 69% were male, and 98% were owned. The epizootic started
      in the southern areas of the city, rapidly involved the entire city, and
      persisted mainly in lower socioeconomic status areas. The area of the city and
      mean household size were significant predictor variables for the population
      density of rabid dogs around household clusters (Poisson linear regression, P <
      0.001 and P = 0.03, resp). Approximately 2.5% of city residents were bitten by
      dogs in 1987, with the rate of reported dog bite injuries being positively
      correlated with mean household size and the proportion of households that owned
      dogs. Visits to the city health centre for evaluation of possible exposures to
      rabies increased by 135% after the start of the epizootic; approximately 273 per
      100,000 city residents were administered a full or partial course of rabies post
      exposure prophylaxis in 1987. Children were at greatest risk for exposures to
      rabies, accounting for 60% of all reported animal bite injuries evaluated at the
      health centre. Also they were more likely than older persons to have received
      bite injuries to the head, face, and neck (odds ratio = 21.6, 95% confidence
      interval = 5.4, 186.5).

PMID- 8261567
TI  - Surveillance for the Expanded Programme on Immunization.
AB  - Surveillance is the foundation of public health practice. This review examines
      the experience of surveillance in the Expanded Programme on Immunization (EPI).
      Surveillance systems include routine reporting, sentinel surveillance, and
      community-based reporting. Data from ongoing surveillance should be linked with
      those from supervision, health facility assessments, population surveys, and
      outbreak investigations to provide information for programme planning,
      implementation, evaluation, and modification. Evaluation of surveillance systems
      should assess the extent to which data are used for policy-making and programme
      improvement, and the simplicity, accuracy, completeness, timeliness and cost of
      the data. The surveillance of vaccine-preventable diseases has evolved as
      programmes mature, to monitor progress towards disease control targets. The
      establishment of goals to reduce measles cases by 90%, eliminate neonatal
      tetanus, and eradicate poliomyelitis has put increased emphasis on the need for
      effective disease surveillance. This opportunity should be taken to promote
      strengthening of national routine systems for disease surveillance, to make them
      effective instruments for prevention and control of diseases of public health
      importance.

PMID- 8261568
TI  - HIV antibody detection in oral fluids.

PMID- 8261569
TI  - Phase I and pharmacokinetic trial of liposome-encapsulated doxorubicin.
AB  - A total of 21 patients with advanced cancer were entered into a phase I study to
      determine the maximum tolerable dose (MTD) of liposome-encapsulated doxorubicin
      (LED) given weekly for 3 consecutive weeks at doses of 20, 30, or 37.5 mg/m2 per
      week. For a comparison of the pharmacokinetic behavior of LED with that of
      standard-formulation doxorubicin, 13 patients received a dose of standard
      formulation doxorubicin 2 weeks prior to the first dose of LED. All doses were
      given by 1-h infusion through a central vein. Toxicity was evaluated in 22
      courses delivered to 17 patients. The MTD with this schedule was 30 mg/m2 per
      week x 3. The single patient treated at 37.5 mg/m2 weekly could not complete the
      entire course due to myelosuppression. At the dose of 30 mg/m2 per week, three of
      eight patients had grade > or = 3 leukopenia. Other toxicities included mild to
      moderate thrombocytopenia, nausea, vomiting, fever, alopecia, diarrhea, fatigue,
      stomatitis, and infection. At the dose of 30 mg/m2 per week, the total
      doxorubicin AUC and peak total doxorubicin concentrations in plasma were 8.75 +/-
      8.80 microM h (mean +/- SD) and 3.07 +/- 1.45 microM, respectively, after LED
      administration. The total doxorubicin AUC and peak total doxorubicin
      concentrations in plasma were 3.92 +/- 2.47 microM h and 2.75 +/- 2.70 microM,
      respectively, after the infusion of standard-formulation doxorubicin. The total
      body clearance of doxorubicin was 18.42 +/- 11.23 l/h after the infusion of LED
      and 31.21 +/- 15.48 l/h after the infusion of standard-formulation doxorubicin.
      The mean elimination half-lives of doxorubicin were similar: 8.65 +/- 5.16 h for
      LED and 7.46 +/- 5.16 h for standard-formulation doxorubicin. Interpatient
      variability in pharmacokinetic parameters as demonstrated by the percentage of
      coefficients of variation was 33%-105%. There was no relationship between the
      percentage of WBC decrease or the duration of WBC suppression and the total
      doxorubicin or doxorubicinol AUC. There was no correlation between the duration
      of leukopenia and drug exposure as reflected by the AUC of liposome-associated
      doxorubicin. LED can be given in doses similar to those of standard-formulation
      doxorubicin and produces acute toxicities similar to those caused by standard
      doxorubicin.

PMID- 8261570
TI  - Antitumor alkylating agents: in vitro cross-resistance and collateral sensitivity
      studies.
AB  - Cell lines resistant to five antitumor alkylating agents (CDDP, PAM, 4-HC, HN2,
      and BCNU) were developed from five parental human tumor lines representative of
      solid tumors with a range of sensitivities to antitumor alkylating agents. The
      parental cell lines were SCC-25 squamous carcinoma of the head and neck, MCF-7
      breast carcinoma, SW2 small-cell lung cancer, SL6 non-small-cell lung carcinoma,
      and G3361 melanoma. Survival curves using colony formation as the endpoint were
      generated for each of the 25 cell lines to each of the five alkylating agents.
      Comparison of the drug concentrations that reduced the survival of the alkylating
      agent-resistant cell lines by 90% (IC90 values) with the IC90 values obtained for
      the corresponding parental cell lines was used as a measure of the
      resistance/sensitivity of the alkylating agent-resistant lines to each drug
      tested. Although cross-resistance among the alkylating agents was generally
      uncommon, several patterns of response emerged. Cross-resistance occurred in 27
      of the 105 determinations and occurred most frequently in the cell lines in which
      resistance was developed to PAM (57%) or BCNU (38%). Cross-resistance to HN2
      occurred most frequently. Collateral sensitivity was equally as common, occurring
      in 25 of the 105 determinations. Collateral sensitivity occurred most frequently
      in the cell lines made resistant to 4-HC. The 4-HC-resistant cell lines were most
      frequently collaterally sensitive to PAM and to BCNU. Cross-resistance developed
      most frequently in the MCF-7 breast carcinoma and SCC-25 squamous-cell carcinoma
      cell lines, whereas collateral sensitivity developed most frequently in the SW2
      small-cell lung cancer line and the G3361 melanoma cell line and least frequently
      in the MCF-7 breast carcinoma cell line and the SL6 non-small-cell lung cancer
      cell line. The implication of these findings for the development of strategies
      for clinical treatment are discussed.

PMID- 8261571
TI  - Evaluation of the genotoxic, cytotoxic, and antitumor properties of Commiphora
      molmol using normal and Ehrlich ascites carcinoma cell-bearing Swiss albino mice.
AB  - The genotoxic, cytotoxic and antitumor properties of Commiphora molmol (oleo gum
      resin) were studied in normal and Ehrlich ascites carcinoma cell-bearing mice. In
      normal mice, the genotoxic and cytotoxic activity was evaluated on the bases of
      the frequency of micronuclei and the ratio of polychromatic to normochromatic
      cells in bone marrow, which was substantiated by the biochemical changes in
      hepatic cells. The antitumor activity of C. molmol was evaluated from the total
      count and viability of Ehrlich ascites carcinoma cells and their nucleic acid,
      protein, malondialdehyde, and elemental concentrations in addition to
      observations on survival and the trend of changes in body weight. The tumors at
      the site of injection were evaluated for histopathological changes. Treatment
      with C. molmol (125-500 mg/kg) showed no clastogenicity but was found to be
      highly cytotoxic in normal mice. The results obtained in the Ehrlich ascites
      carcinoma cell-bearing mice revealed the cytotoxic and antitumor activity of C.
      molmol which was found to be equivalent to those of the standard cytotoxic drug
      cyclophosphamide. On the basis of the nonmutagenic, antioxidative, and cytotoxic
      potential of C. molmol as observed in the present study, its use in cancer
      therapy seems to be appropriate and further investigations are suggested.

PMID- 8261572
TI  - A phase I trial of high-dose continuous-infusion hydroxyurea.
AB  - Hydroxyurea inhibits ribonucleotide reductase, resulting in depletion of
      intracellular deoxynucleotide pools and inhibition of DNA repair. It has been
      used in a variety of malignancies and is usually given orally. Deoxynucleotide
      depletion is directly related to the concentration of and duration of exposure to
      hydroxyurea; thus, prolonged continuous infusion may result in increased
      therapeutic efficacy. A total of 30 patients were treated on this trial, designed
      to determine the maximum tolerated doses (MTD) of intravenous hydroxyurea given
      as a 24- or 48-h continuous infusion. The MTD for the 24-h infusion was 13,520
      mg/m2 following a bolus of 1,690 mg/m2, and the mean (+/- SD) plasma steady-state
      concentration was 1.93 +/- 0.52 mM. For the 48-h infusion, the MTD was 17,576
      mg/m2 following a bolus of 2,197 mg/m2 and the mean steady-state level was 1.43
      +/- 0.31 mM. The dose-limiting toxicity on both schedules was marrow suppression
      manifesting as neutropenia and thrombocytopenia. Pharmacokinetic analysis
      revealed decreasing clearance with increasing dose, implying that drug
      elimination is saturable. Pharmacodynamic analysis showed a slight correlation
      between steady-state plasma levels and the degree of marrow suppression.

PMID- 8261573
TI  - Effect of pH and moderate hyperthermia on doxorubicin, epirubicin and
      aclacinomycin A cytotoxicity for Chinese hamster ovary cells.
AB  - The influence of extracellular pH on the cytotoxicity of the anthracyclines
      doxorubicin, epirubicin, and aclacinomycin A was examined at 37 degrees C and 41
      degrees C in tissue culture. Chinese hamster ovary (CHO) cells were exposed for a
      total of 24 h to anthracyclines at doses ranging between 0.12 and 0.69 nmol/ml at
      pH 7.4, 6.7, and 6.4 and at 37 degrees C. Temperature elevation to 41 degrees C
      was carried out for 3 h after the initiation of the drug treatment. Doxorubicin
      and epirubicin were about equally cytotoxic in the pH range examined at both
      temperatures. Aclacinomycin A demonstrated a higher cytotoxicity at pH 7.4 and 37
      degrees C only at low doses. At low pH, however, aclacinomycin A was increasingly
      more effective with increasing dose as compared with doxorubicin and epirubicin.
      At 41 degrees C and at higher doses aclacinomycin A was even less cytotoxic than
      doxorubicin or epirubicin. Doxorubicin and epirubicin were less effective at
      lower pH. However, aclacinomycin A at doses of greater than 0.25 nmol/ml was more
      cytotoxic at low pH. Moderate hyperthermia did not increase the cytotoxicity of
      the three drugs at low pH, except for aclacinomycin A at doses of less than 0.25
      nmol/ml. At pH 7.4, aclacinomycin A was even less effective at the elevated
      temperature. At doses of greater than 0.25 nmol/ml, moderate hyperthermia
      decreased the cytotoxicity of aclacinomycin A at low pH.

PMID- 8261574
TI  - Etoposide-resistant human colon and lung adenocarcinoma cell lines exhibit
      sensitivity to homoharringtonine.
AB  - Human colon (HCT116/VP48) and lung (A549B/VP29) adenocarcinoma cell lines
      selected for resistance to etoposide exhibited modified patterns of multi-drug
      resistance (MDR) that included a differential sensitivity to other DNA
      topoisomerase II inhibitors and to the plant alkaloids homoharringtonine,
      vinblastine, and vincristine. The resistance and cross-resistance drug phenotype
      of the A549B/VP29 cell line was different from that of the HCT116/VP48 cell line.
      The HCT116/VP48 cell line was 50-fold resistant to etoposide and 30-fold
      resistant to teniposide. The degree of resistance to other DNA topoisomerase II
      inhibitors was of a lower magnitude: Adriamycin, 9-fold; daunomycin, 3-fold; 4'
      [(9-acridinyl)-amino]-methanesulfone-m-anisidide (m-AMSA), 3-fold; and
      actinomycin D, 6-fold. The HCT 116/VP48 cell line exhibited a 7-fold resistance
      to vincristine and a 2-fold resistance to vinblastine but was sensitive to homo
      harringtonine. The A549B/VP29 cell line was 5-fold resistant to etoposide and 2
      fold resistant to teniposide. The A549B/VP29 cell line exhibited a 2-fold
      resistance to Adriamycin but was sensitive to daunomycin and showed a 3-fold
      resistance to m-AMSA. This cell line was sensitive to actinomycin D. The
      A549B/VP29 cell line was 2-fold resistant to vinblastine and sensitive to
      homoharringtonine. Both cell lines (HCT116/VP48 and A549/VP29) exhibited no
      amplification of the human mdr1 DNA sequence, the 4.3-kb P-glycoprotein
      transcript, or the membrane P-glycoprotein. The sensitivity of cells exhibiting
      an MDR phenotype not mediated by P-glycoprotein suggests a potential use for
      homoharringtonine in treating tumors with this type of drug resistance.

PMID- 8261575
TI  - Phase II study of carboplatin, cisplatin, and vindesine in advanced non-small
      cell lung cancer.
AB  - Cisplatin in combination with vindesine has been widely used for the treatment of
      advanced non-small-cell lung cancer (NSCLC), producing an overall response rate
      of 32%. We conducted a phase II study to examine whether the addition of
      carboplatin to the combination of cisplatin and vindesine would improve the
      antitumor activity of the two platinum agents in advanced NSCLC without
      increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were
      given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on
      day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial
      response, for an overall response rate of 30% (95% confidence interval, 17%-47%).
      The median duration of response was 12 weeks, and the median survival duration
      for all patients was 38 weeks. The major toxicity was hematologic: leukopenia
      (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or
      = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3
      toxicity was observed in only 4 patients (10%). Nonhematologic toxicities
      consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%)
      and WHO grade > or = 2 alopecia in 11 patients (28%). No significant
      nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition
      of carboplatin to the combination of cisplatin and vindesine does not improve
      antitumor activity in patients with advanced NSCLC.

PMID- 8261576
TI  - Reversal of acquired cisplatin resistance by nicotinamide in vitro and in vivo.
AB  - At a concentration of 2.5 mM, nicotinamide (NA), an inhibitor of poly(ADP-ribose)
      polymerase (PARP), significantly potentiated the cytotoxicity of cisplatin (DDP)
      in a DDP-resistant rat ovarian tumor cell line (O-342/DDP) in vitro, whereas the
      same treatment had no substantial effect on DDP's cytotoxic activity against the
      DDP-sensitive parental line (O-342). Furthermore, in a nude mouse model where the
      O-342/DDP tumor grew intraperitoneally, whereas DDP given alone at 1 mg/kg x 3
      exhibited no antitumor activity as compared with control values due to the
      resistance, NA given at a nontoxic dose (5 mmol/kg x3) significantly increased
      the mean survival time (MST) of the tumor-bearing NMRI nude mice from 20.7 days
      in the DDP-treated group to 29.0 days in the combination group. Mechanism studies
      showed that endogenous PARP activity (incorporation of tritiated nicotinamide
      adenine dinucleotide, [3H]-NAD) was 2.6 times higher in O-342/DDP than in O-342
      cells and that the presence of 2.5 mM NA during the incubation with the isotope
      resulted in 73.3% inhibition of the enzyme activity in O-342/DDP cells but in
      only about 30% inhibition in the sensitive line. However, treatment with NA
      during and after DDP exposure failed to produce any significant effect on the
      formation of DNA single-strand breaks (SSB) but decreased the induction of DNA
      interstrand cross-links (ISCL) by DDP in the sensitive and resistant cell lines.
      These results suggest that NA might have some clinical potential in reversing DDP
      resistance, and further studies are therefore warranted to confirm the resistance
      reversing effect of NA in other DDP-resistant cell lines.

PMID- 8261577
TI  - Sequence-dependent growth-inhibitory effects of the in vitro combination of
      fluorouracil, cisplatin, and dipyridamole.
AB  - The present study was designed to analyze the growth-inhibitory effects of the
      combination of fluorouracil (FUra), cisplatin (CDDP), and dipyridamole (DP).
      These toxic effects were assessed on the human breast-carcinoma cell line MCF-7
      using the MTT (tetrazolium bromide) assay in 96-well culture dishes. Data were
      analyzed using the median-effect principle. The drug combinations tested included
      FUra concentrations ranging from 0.8 to 800 nmol/l, CDDP concentrations of 0.3-30
      mumol/l, and DP concentrations of 2-200 mumol/l. A total of 189 different
      experimental conditions were tested, including different sequences of
      administration, with being DP applied before, simultaneously with, or after the
      two antitumor drugs. Synergistic cytotoxic interactions were found between FUra
      and CDDP, FUra and DP, and CDDP and DP as well as when the three drugs were
      combined. The sequence of exposure did not influence the growth-inhibitory
      activity of the combination FUra-CDDP but altered the effect of combinations of
      either FUra or CDDP with DP, since at lower concentrations the effect shifted
      from synergism to antagonism when DP was added simultaneously with CDDP and after
      the two antitumor drugs. However, the interaction was shown to be truly
      synergistic by median-effect analysis when the two antitumor drugs were
      simultaneously associated, with no change in the synergistic effect being
      observed for the three DP administration sequences.

PMID- 8261578
TI  - Postoperative PSK and OK-432 immunochemotherapy for patients with gastric cancer.
AB  - We evaluated the effects of chemotherapy given postoperatively with and without
      immunomodulators on the survival of patients who had undergone resection for
      gastric cancer. We conducted a retrospective survey of data on 963 Japanese
      patients treated at our department of surgery between 1965 and 1987. Data related
      to the duration of postoperative survival were calculated for those who received
      chemotherapy, i.e. an individualized combination of various agents given with or
      without the immunomodulators PSK, a protein extract of the fungus Coriolus
      versicolor, and/or OK-432, a preparation of an attenuated strain of Streptococcus
      (immunochemotherapy). Postoperative immunochemotherapy was more often prescribed
      for patients with advanced disease. The survival of patients who received
      immunochemotherapy was shorter than that of patients who received only
      chemotherapy. In a subgroup of patients adjusted for disease stage, the survival
      of those on chemotherapy versus immunochemotherapy did not differ significantly
      at any stage. For optimal results, a protocol for postoperative
      immunochemotherapy needs to be designed and investigated prospectively and
      according to the stage of gastric cancer. The stage III gastric cancers seem
      amenable to a favorable response.

PMID- 8261579
TI  - Pulmonary distribution of vinorelbine in patients with non-small-cell lung
      cancer.
AB  - Vinorelbine (Navelbine, NVB) is a new semi-synthetic vinca alkaloid that is
      currently used in the treatment of advanced breast cancer and advanced non-small
      cell lung cancer (NSCLC). In this study we investigated the tumoral and healthy
      pulmonary tissue concentrations of NVB in previously untreated NSCLC patients
      undergoing surgery. A total of 13 patients (mean age, 60 years; range, 42-70
      years) were included and received NVB (20 mg/m2) at 1 h (mean, 1.1 h; SD, 0.2 h;
      n = 6 patients) and 3 h (mean, 3.0 h; SD, 0.6 h; n = 7 patients) before tumor
      resection. A tumoral and adjacent healthy lung-tissue specimen as well as
      simultaneously sampled serum were analyzed for NVB by high-performance liquid
      chromatography (HPLC). NVB levels were much higher in tissue than in serum (up to
      300-fold). The tissue/serum ratio increased between the 1-h sampling time (range,
      0.1-100) and the 3-h time point (range, 10-300). In all patients but two, NVB
      concentrations were lower in tumors than in healthy lung tissue. The
      tumor/healthy tissue ratio ranged from 0.06 to 1.3 (median, 0.09) at 1 h and from
      0.18 to 1.1 (median, 0.55) at 3 h. This ratio increased between the 1-h sampling
      time and the 3-h time point as a consequence of increasing tumor levels (median,
      50.4 ng/g at 1 h and 278 ng/g at 3 h). In four patients, concentrations could be
      measured in necrotic and peripheral tumor zones, showing lower values in necrotic
      areas. Thus, these data indicate that NVB is highly distributed in lung tissue,
      with the disposition rate being slower in tumor tissue than in healthy parenchyma
      during the first 3 h.

PMID- 8261580
TI  - Activity of continuous-infusion 5-fluorouracil in patients with advanced
      colorectal cancer clinically resistant to bolus 5-fluorouracil.
AB  - We have recently demonstrated that continuous-infusion (CI) 5-fluorouracil (FU)
      eradicates human colon carcinoma cells made resistant to bolus FU in vitro. In
      addition, in the same experimental system, the mechanisms of resistance to pulse
      and CI FU were found to be different. These observations led us to test the
      clinical activity of a standard regimen of CI FU (300 mg/m2 per day) in a cohort
      of 15 patients with advanced measurable colorectal cancer who were in progression
      after having failed to respond to bolus treatment with FU alone (3 patients) or
      FU combined with high-dose 6-S-leucovorin (LV) (12 patients). The median age of
      the patients was 68 years, and their median Eastern Cooperative Oncology Group
      performance status (ECOG PS) was 1. No myelotoxicity was observed. Mild diarrhea,
      mucositis, and vomiting occurred in 32%, 26%, and 19% of the patients,
      respectively, with no WHO grade 3 or 4 episodes being noted. In all, 6 of 15
      patients complained of hand-foot syndrome, which was severe in 2 instances,
      lasting approximately 1 week. Overall, 1 partial response and 6 instances of
      disease stabilization, including 3 minor responses, were obtained both in
      patients who had been pretreated with pulse FU alone and in patients who had
      failed first-line treatment with FU + LV. Finally, 8 patients failed CI FU. In
      conclusion, these results, obtained in patients who were clearly progressing
      after having failed first-line treatment, support our experimental finding that
      resistance to bolus FU may be overcome by CI FU and extend this possibility to
      patients who are resistant to bolus treatment with FU + LV.

PMID- 8261582
TI  - Effects of temperature and sodium on myocardial and hepatocellular fatty acid
      uptake.
AB  - Fatty acid influx into human myocardium was studied in 15 patients during the
      cooling phase of cardiopulmonary bypass at myocardial temperatures of 37 degrees
      to 25 degrees C. The fitting of the data to a functional relation, developed in
      this study, revealed fatty acid influx to be a temperature-dependent saturable
      process corresponding to a Michaelis-Menten constant (Km) at 37 degrees C of 0.26
      +/- 0.084 mumol/g, a maximal fatty acid influx velocity (Vmax) at 37 degrees C of
      0.28 +/- 0.045 mumol/g per minute, activation energy for fatty acid binding to
      the putative carrier (E) of 23.8 +/- 5.6 kcal/mol, and a free energy for
      conformational change of the carrier (U) of 10.9 +/- 8.0 kcal/mol. In short-term
      cultured hepatocytes, Km increased in the absence of Na+ from 171 +/- 48 to 301
      +/- 71 nmol/L, and Vmax of [3H]oleate decreased from 1063 +/- 69 to 847 +/- 68
      pmol/min per milligram protein. The fitting of these data to a functional
      relation revealed a transmembrane potential-dependent component of parameters E
      and U to be -0.479 and -0.374 kcal/mol, respectively. It is proposed that for
      fatty acid influx a protonated fatty acid form is preferred that consists of a
      Na+ complex with the mesomeric form of nondissociated fatty acid from which Na+
      and H+ are released during collision with the carrier.

PMID- 8261583
TI  - Potent vasoconstriction mediated by endothelin ETB receptors in canine coronary
      arteries.
AB  - Endothelin (ET) 1 is a powerful vasoconstrictor of coronary arteries and may play
      a role in coronary spasm, atherosclerosis, and myocardial infarction. Previous
      studies have demonstrated that intracoronary ET caused marked vasoconstriction of
      the coronary circulation; however, it remains unclear which ET receptor types are
      present and which of these receptors mediate this vasoconstriction. To
      characterize the ET receptors present in dog coronary arteries, competition
      binding assays with radiolabeled ET-1 using ET-1, ET-3, ETA receptor antagonist
      BQ-123, and sarafotoxin S6c were performed. Three binding sites were apparent in
      the left circumflex coronary artery: an ETA receptor, a high-affinity ETB
      receptor, and a lower-affinity ETB receptor. To investigate the in vivo effects
      of ETB receptor stimulation, intracoronary sarafotoxin S6c, a highly selective
      ETB agonist, was administered in anesthetized open-chest dogs in a constant
      pressure coronary artery perfusion model. Sarafotoxin S6c doses of 0.1 and 0.3
      microgram caused a transient pronounced decrease in coronary resistance. Doses of
      1.0 and 3.0 micrograms caused marked decreases in coronary diameter and blood
      flow, as well as myocardial segmental shortening. These effects of sarafotoxin
      S6c were not inhibited by constant infusion of BQ-123. The present study
      demonstrates the presence of ETB receptors in the canine coronary circulation
      that can mediate both vasodilation and vasoconstriction. These findings have
      important implications for an understanding of the pathophysiological function of
      ET in the coronary vasculature and for the development of therapeutically
      effective ET antagonists.

PMID- 8261584
TI  - Nitrate tolerance in vivo is not associated with depletion of arterial or venous
      thiol levels.
AB  - Results from in vitro experiments suggest that development of nitrate tolerance
      is due to a depletion of vascular thiol compounds (ie, cysteine and glutathione
      [GSH]) necessary for the bioconversion of organic nitrates. However, it is
      unknown whether in vivo tolerance development is associated with changes in thiol
      levels. This study measures plasma and vessel tissue GSH and cysteine levels in
      nontolerant rats, nitrate-tolerant rats, and rats treated with the two
      characteristically different thiol donors N-acetyl-L-cysteine and L-2
      oxothiazolidine-4-carboxylic acid (OXO). Chronically catheterized conscious rats
      received an intravenous infusion of either nitroglycerin (NTG, 0.2 mg/h) or
      matching placebo for 3 days. At day 3, the hypotensive effect of 2.5 mg NTG/kg
      was decreased by 74 +/- 6% (mean +/- SEM, P < .05) in the NTG-treated group (n =
      7), indicating the development of tolerance. No change in the hypotensive effect
      of NTG was seen in the placebo group (n = 6, P > .05). Hemodynamic tolerance is
      not associated with changes in aorta cysteine or GSH levels as compared with the
      placebo group (cysteine, 77 +/- 14 versus 57 +/- 11 [mean + SEM] nmol/g; GSH, 414
      +/- 62 versus 399 +/- 89 nmol/g; P > .05). However, the increase in vascular
      thiol levels seen after OXO treatment in nontolerant rats is completely absent in
      nitrate-tolerant animals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261581
TI  - WR2721 as a modulator of cisplatin- and carboplatin-induced side effects in
      comparison with other chemoprotective agents: a molecular approach.
AB  - Cisplatin is an active cytostatic that became successful in the treatment of
      several types of solid tumours after its nephrotoxic potential was controlled by
      hydration and diuresis. Thiol compounds were tested to reduce further cisplatin
      induced nephrotoxicity. Thiosulphate is rapidly excreted by the kidneys and
      protects against cisplatin-induced nephrotoxicity by inactivating reactive
      platinum species in the kidney. Due to inactivation of cisplatin in the
      circulation, thiosulphate also interferes with its antitumour activity.
      Therefore, it is mainly used in two-route schedules, whereby cisplatin is
      delivered locally to the tumour (i.p. or i.a.) while systemic (i.v.) thiosulphate
      protects the kidneys. Diethyldithiocarbamate was shown to protect against
      cisplatin-induced nephrotoxicity in several animal models by reversing cellular
      damage. However, in the clinic it has been less successful, partly due to its
      central nervous system toxicity. The endogenous thiol compounds glutathione and
      metallothionein have been shown to reduce cisplatin-induced toxicity both in
      animal models and in clinical trials. However, the results are rather preliminary
      and a reduction in therapeutic efficacy may be expected, for both glutathione and
      metallothionein have been reported to be involved in platinum resistance. The
      thioether methionine has been shown to reduce cisplatin-induced nephrotoxicity in
      animal models but it has not yet been tested in the clinic. Cisplatin-induced
      acute emesis can be sufficiently controlled with a new class of 5
      hydroxytryptamine-3 (5HT3)-receptor blockers, but delayed emesis remains a
      problem. High-dose cisplatin regimens with protection of the kidneys induces
      ototoxicity, peripheral neuropathy and myelotoxicity, which become dose-limiting.
      Neurotoxicity was partly reversed by the neurogenerative agent ORG2766, but this
      agent does not reduce other cisplatin-induced toxicities. Therefore, an agent
      capable of protecting multiple non-tumour tissues is needed. Carboplatin is a
      second-generation analogue of cisplatin with less nephro-, neuro- and
      ototoxicity. Carboplatin is at least as active as cisplatin at its maximum
      tolerated dose, which is defined by its myelotoxicity. Protection from
      carboplatin-induced myelotoxicity may be controlled by autologous bone marrow
      transplantation and/or hematopoietic growth factor infusions. High-dose
      carboplatin schedules may cause nephrotoxicity, neurotoxicity and ototoxicity.
      Again, the protection of multiple non-tumour tissues is needed. WR2721 appears to
      be such a modulating agent capable of protecting multiple non-tumour tissues. It
      was shown to be preferentially metabolized and taken up as the thiol metabolite
      WR1065 by non-tumour tissues as compared with (hypoxic) solid tumours. It was
      shown to protect mice from cisplatin-induced nephrotoxicity and from cisplatin-
      and carboplatin-induced myelotoxicity without interfering with the antitumour
      activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8261585
TI  - Properties of a protein kinase C-activated chloride current in guinea pig
      ventricular myocytes.
AB  - Cardiac ventricular myocytes from several species, including the guinea pig,
      possess a cAMP-dependent protein kinase A (PKA)-activated Cl- channel. In the
      present study, the properties of a protein kinase C (PKC)-activated Cl- current
      were studied in isolated guinea pig ventricular myocytes using the whole-cell
      arrangement of the patch-clamp technique. Intracellular dialysis of ventricular
      cells with PKC resulted in the activation of a large background current that
      displayed time-independent kinetics. In the presence of 146 mmol/L external Cl-
      and 71 mmol/L internal Cl-, the reversal potential (Erev) of the background
      current (-17 +/- 1 mV) was close to that of the Cl- equilibrium potential (-18
      mV), and the current versus voltage relation for the current was outward
      rectifying in shape. When [Cl-]i or [Cl-]o was reduced by substitution of Cl-
      with aspartic acid, Erev for the background current shifted in a manner expected
      for a Cl(-)-selective channel. Based on Erev measurements, the permeability
      sequence for this PKC-activated Cl- channel was determined to be SCN- > I- > Br-
      congruent to Cl-. The PKC-activated Cl- current was not inhibited by the Cl-
      channel blocker 4,4'-dinitrostilbene-2,2'-disulfonic acid (100 mumol/L) but could
      be blocked by anthracene-9-carboxylic acid (1 mmol/L). Activation of the current
      was abolished in the presence of the PKC inhibitor staurosporine (2.5 mumol/L).
      Under conditions designed to cause a maximal activation of the Cl- channels by
      PKC, the addition of forskolin (1 mumol/L) to stimulate PKA caused only a slight
      further increase in the amplitude of the Cl- current. Thus, PKC activates a Cl-
      channel in guinea pig ventricular cells with properties similar but not identical
      to the PKA-activated channel.

PMID- 8261586
TI  - Exaggerated vascular response due to endothelial dysfunction and role of the
      renin-angiotensin system at early stage of renal hypertension in rats.
AB  - We investigated whether endothelial dysfunction might contribute to the
      exaggerated vasoconstriction that was induced by the administration of
      norepinephrine at the early stage of one-kidney, one-clip renal hypertension
      (1K1C) in rats. We also studied the role of the renin-angiotension system in this
      phenomenon. Male Wistar rats were killed 48 hours after the induction of renal
      artery stenosis or sham operation, and ring preparations of the thoracic aorta
      were obtained. The isometric contraction and relaxation of aortic strips produced
      by norepinephrine and acetylcholine, respectively, were recorded with a force
      displacement transducer. The aorta of 1K1C rats showed a significantly (P < .05)
      exaggerated contractile response to norepinephrine as compared with that of
      control rats. Rubbing the endothelium and treatment with methylene blue or NG
      monomethyl L-arginine acetate augmented the contractile responses to
      norepinephrine to a greater extent in control rats than in 1K1C rats; therefore,
      the responses of the groups did not differ significantly. In the second
      experiment, rats received 0.05% captopril, 0.02% enalapril, or 0.02% nicardipine
      in the drinking water for 1 day before and for 48 hours after the induction of
      renal artery stenosis or sham operation. The increased contractile responses of
      the aorta to norepinephrine in 1K1C rats were normalized to the level of the
      control rats by treatment with either captopril or enalapril but not with
      nicardipine. These results suggest that the endothelial dysfunction may
      contribute to the exaggerated norepinephrine-induced vasoconstriction observed in
      the 1K1C rats and that angiotensin I-converting enzyme inhibitors can restore the
      endothelial function.

PMID- 8261587
TI  - Importance of metabolic inhibition and cellular pH in mediating preconditioning
      contractile and metabolic effects in rat hearts.
AB  - The pathophysiological mechanisms by which brief periods of flow interruption
      before a prolonged ischemic period, ischemic preconditioning (IPC), increase
      myocardial tolerance to ischemia and improve myocardial function during
      reperfusion are not completely understood. To test whether short periods of
      metabolic inhibition in the absence of a flow reduction induce similar protective
      effects, we studied cardiac function and metabolism using 31P nuclear magnetic
      resonance spectroscopy in isolated isovolumic rat hearts. Fifteen hearts
      underwent IPC, consisting of two 5-minute ischemia-reperfusion cycles (IPC
      group); 18 hearts underwent brief metabolic inhibition by exposure to two 5
      minute infusions of 10 mmol/L sodium cyanide (CN group); and 15 hearts served as
      controls. Subsequently all hearts were subjected to 30 minutes of total global
      ischemia at 37 degrees C followed by reperfusion. At the end of the ischemic
      period, creatine phosphate and ATP levels did not differ among the groups.
      Cellular pH, however, plateaued at a higher level in the CN group (6.51 +/- 0.03)
      and IPC group (6.12 +/- 0.06) than in the control group (5.84 +/- 0.01, P <
      .001). IPC and CN hearts had better functional and metabolic recovery than the
      control hearts. Improved contractile recovery correlated with coronary flow rates
      at reperfusion (r = .7, P < .001) and with pHi values at 30 minutes of ischemia
      (r = .8, P < .001) but not with increased ATP levels during ischemia. Additional
      control hearts were reperfused at 15 mL/min so as to match the flow rates of IPC
      and CN groups, but this did not result in improved performance. To test the
      hypothesis that the preconditioning effect was related to pHi during ischemia,
      additional IPC and CN hearts underwent the same preconditioning protocol, except
      that the cellular pH at the end of the ischemic period was lowered by the use of
      hypercarbic superfusion during ischemia or by the use of bicarbonate-free
      perfusate just before sustained ischemia. Both of these interventions resulted in
      significantly lower contractile and metabolic recoveries than those observed in
      other IPC and CN hearts. Therefore, the preconditioning effect does not require
      reduced coronary flow but can be effectively elicited by metabolic inhibition per
      se in this model. The protective effect is not dependent on preservation of
      global myocardial energy stores but, rather, on reduced acidosis during the
      prolonged ischemic period.

PMID- 8261588
TI  - Time course of flow-induced smooth muscle cell proliferation and intimal
      thickening in endothelialized baboon vascular grafts.
AB  - Polytetrafluoroethylene (PTFE) grafts placed into the arterial circulation of
      baboons for 8 weeks under high blood flow (HF) conditions develop a thin intima
      composed of smooth muscle cells (SMCs) and extracellular matrix beneath an
      endothelial monolayer. When these grafts are returned abruptly to normal flow
      (NF), they develop marked intimal thickening within 1 month. The mechanisms
      underlying this thickening are unclear. We studied the SMC response to altered
      flow by placing bilateral aortoiliac PTFE grafts into baboons with bilateral
      femoral arteriovenous fistulas. After 8 weeks, one fistula was closed, returning
      the graft flow on that side to NF. The opposite graft remained under HF
      conditions. Flow differences were monitored with duplex ultrasound (for all
      grafts: NF, 135 +/- 21 [mean +/- SEM] mL/min; HF, 507 +/- 35 mL/min; P < .001).
      Grafts were removed 2, 4, 7, 14, or 28 days later (five animals per group).
      Endothelial coverage, as assessed by scanning electron microscopy, was intact in
      each graft. Intimal area and SMC number increased progressively in NF grafts
      through 28 days (for area: NF, 3.0 +/- 0.3 mm2; HF, 0.6 +/- 0.2 mm2; P < .001;
      and for SMCs per cross section: NF, 11.8 +/- 1.1 x 10(3); HF, 2.6 +/- 1.0 x
      10(3); P < .002). Intimal SMC proliferation (thymidine labeling) was increased
      significantly in NF grafts at 4 and 7 days (at 4 days: NF, 5.9 +/- 1.5%; HF, 1.4
      +/- 0.6%; P < .05). Extracellular matrix accounted for an equal proportion of
      intimal mass in NF and HF grafts (percent matrix at 28 days: NF, 62.9 +/- 1.6%;
      HF, 63.7 +/- 4.7%; P = NS). We conclude that intimal thickening in this model of
      flow-induced vascular remodeling is due to increased SMC proliferation and
      accumulation of SMCs with a proportionate amount of extracellular matrix.

PMID- 8261589
TI  - A functional ryanodine-sensitive intracellular Ca2+ store is present in vascular
      endothelial cells.
AB  - The presence of the ryanodine receptor was recently demonstrated in vascular and
      endocardial endothelium, but its function has not been established. We
      investigated whether functional ryanodine-sensitive Ca2+ stores are present in
      cultured endothelial cells from rat aorta (RAECs), human aorta (HAECs), human
      umbilical vein (HUVECs), and bovine pulmonary artery (BPAECs) and what role these
      may play in intracellular Ca2+ regulation. Under resting conditions, HAECs,
      BPAECs, and HUVECs demonstrated a slow increase in intracellular Ca2+ (indexed by
      indo 1 fluorescence) on exposure to 5 mumol/L ryanodine, whereas RAECs did not.
      However, after an initial bradykinin exposure in RAECs, ryanodine markedly
      blunted the rapid increase in Ca2+ on a second exposure to bradykinin. In HUVECs,
      ryanodine in buffer with 1.5 mmol/L Ca2+ did not inhibit the agonist-sensitive
      Ca2+ increase, whereas it blunted the rapid increase in Ca2+ on histamine
      exposure in buffer with 5 mmol/L Ca2+, suggesting that increasing [Ca2+] enhances
      the binding of ryanodine to its receptor. Thus, functional ryanodine-sensitive
      Ca2+ stores are present in vascular endothelial cells. These appear to be
      involved in regulation of Ca2+ storage and release from agonist-sensitive
      intracellular compartments.

PMID- 8261590
TI  - Actions of vasoactive intestinal peptide and neuropeptide Y on the pacemaker
      current in canine Purkinje fibers.
AB  - We have investigated the actions of vasoactive intestinal peptide (VIP) and
      neuropeptide Y (NPY) on the pacemaker current (I(f)) in canine Purkinje fibers.
      On voltage pulses to the middle of the I(f) activation range, VIP reversibly
      increases I(f), whereas NPY reversibly decreases I(f). A three-pulse voltage
      protocol suggests that VIP shifts I(f) activation in the positive direction and
      that NPY shifts I(f) activation in the negative direction on the voltage axis
      without changing maximal I(f) conductance. These effects of VIP and NPY on I(f)
      are exerted through their specific peptide receptors, since the effects are
      blocked by VIP and NPY receptor antagonists. VIP and NPY are colocalized in
      cardiac parasympathetic and sympathetic nerve endings, respectively, and can be
      released preferentially on high and long-lasting nerve stimulation. Given this
      colocalization and frequency-dependent release, these results suggest a role for
      these neuropeptides in controlling cardiac I(f) and consequently heart rate.

PMID- 8261591
TI  - Shear stress-induced reorganization of the surface topography of living
      endothelial cells imaged by atomic force microscopy.
AB  - We report the first topographical data of the surface of living endothelial cells
      at sub-light-microscopic resolution, measurements essential for a detailed
      understanding of force distribution in the endothelium subjected to flow. Atomic
      force microscopy was used to observe the surface topography of living endothelial
      cells in confluent monolayers maintained in static culture or subjected to
      unidirectional shear stress in laminar flow (12 dyne/cm2 for 24 hours). The
      surface of polygonal unsheared cells was smooth, with mean excursion of surface
      undulation between peak height (over the nucleus) and minima (at intercellular
      junctions) of 3.4 +/- 0.7 microns (mean +/- SD); the mean height to length ratio
      was 0.11 +/- 0.02. In cells that were aligned in the direction of flow after a 24
      hour exposure to laminar shear stress, height differentials were significantly
      reduced (mean, 1.8 +/- 0.5 micron), and the mean height to length ratio was 0.045
      +/- 0.009. Calculation of maximum shear stress and maximum gradient of shear
      stress (delta tau/delta x, where tau is shear stress at the cell surface) at
      constant flow velocity revealed substantial streamling of aligned cells that
      reduced delta tau/delta x by more than 50% at a nominal shear stress of 10
      dyne/cm2. Aligned cells exhibited ridges extending in the direction of flow that
      represented imprints of submembranous F-actin stress-fiber bundles mechanically
      coupled to the cell membrane. The surface ridges, approximately 50 nm in height
      and 200 to 1000 nm in width, were particularly prominent in the periphery of the
      aligned cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261592
TI  - Brefeldin A defines distinct pathways for atrial natriuretic factor secretion in
      neonatal rat atrial and ventricular myocytes.
AB  - The intracellular pathways for basal atrial natriuretic factor (ANF) secretion
      from the heart and their correlation with ANF processing to the active form were
      characterized in cultured neonatal rat atrial and ventricular myocytes. Brefeldin
      A, a fungal antimetabolite that blocks transport of newly synthesized proteins
      from the endoplasmic reticulum, was used to inhibit nascent protein trafficking.
      Thus, release of newly synthesized hormone was blocked, but release of stored
      hormone was unaffected. Whereas brefeldin A inhibited basal ventricular ANF
      release to 10% of the control value, basal ANF release from atrial cells was
      enhanced. Furthermore, basal atrial ANF secretion was inhibited by agents
      preventing myocyte depolarization, Ca2+ influx, release of Ca2+ from
      intracellular stores, or activation of protein kinase C, whereas ventricular ANF
      secretion was unaffected by these agents. Brefeldin A did not alter maturational
      processing of pro-ANF to ANF-(99-126) in either atrial or ventricular cultures.
      These findings indicate that (1) basal secretion of ANF from ventricular cells
      relies largely on newly synthesized hormone and is probably constitutive, (2)
      basal secretion of ANF from atrial cells is independent of transport of newly
      synthesized protein and occurs via a regulated pathway controlled at least in
      part by signaling changes associated with myocyte beating, and (3) processing of
      pro-ANF occurs either with constitutive or regulated secretion of hormone, which
      may indicate multiple cellular locations for the processing enzyme.

PMID- 8261593
TI  - Molecular basis of cardiac troponin T isoform heterogeneity in rabbit heart.
AB  - In the rabbit heart, multiple isoforms of cardiac troponin T (cTnT1 through
      cTnT5, from largest in size to smallest), a protein essential for calcium
      regulated myofibrillar ATPase activity, have been identified, and a correlation
      has been found between these isoforms and myofilament sensitivity to calcium. We
      have sought to establish the molecular basis of this diversity. Restriction
      digest analysis of genomic DNA has indicated that the rabbit cTnT gene is a
      single-copy gene. cTnT cDNA clones were isolated from cDNA libraries, yielding a
      consensus sequence for the protein. Newborn rabbit heart cDNAs, obtained using
      the reverse-transcriptase polymerase chain reaction (RT-PCR), were amplified
      using primers derived from this cDNA. Three full-length cDNAs that differed by
      the inclusion or exclusion of three short nucleotide sequences within the cDNAs
      were obtained. Amplification in the 5' half of the cDNAs confirmed that multiple
      cTnT products arose because of the variable inclusion of an 18- and a 30-nt
      sequence. The 30-nt sequence has homology with previously described alternatively
      spliced exons in rat and chicken cTnT, whereas the 18-nt sequence has not been
      described previously. RT-PCR in the 3' half of the cDNAs confirmed an additional
      region of heterogeneity: the presence, in part or in full, or absence of a 9-nt
      region, which matches the alternatively spliced exon 12 described for rat cTnT.
      In vitro transcription and translation of four cDNA clones containing both the 18
      and 30-nt sequences, the 30-nt sequence, the 18-nt sequence, or neither
      generated protein isoforms that comigrated with cTnT1, cTnT2, cTnT3, and cTnT4,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261594
TI  - Presence of chloride-formate exchange in vascular smooth muscle and cardiac
      cells.
AB  - The presence of chloride-formate anion exchange in vascular smooth muscle cells
      (VSMCs) and cardiac myocytes was investigated. Imposing an outward chloride
      gradient in sarcolemmal microsomes isolated from canine aorta stimulated
      [14C]formate uptake compared with the absence of a chloride gradient (24.3 +/-
      2.33 versus 9.8 +/- 1.41 pmol/mg protein for 30 seconds, P < .03) and induced
      transient uphill [14C]formate uptake. The chloride-formate exchange was
      significantly inhibited in the presence of 1 mmol/L 4,4'-diisothiocyanostilbene
      2,2'-disulfonic acid (DIDS) or furosemide (57% and 61%, respectively). Incubation
      of rat cultured VSMCs in a medium containing [14C]formate resulted in uptake of
      formate that was significantly DIDS and furosemide sensitive (79.34 +/- 2.47,
      43.03 +/- 2.37, and 44.65 +/- 1.68 pmol/mg protein for 4 minutes in control,
      DIDS, and furosemide groups, respectively). Preincubation of the VSMCs in
      chloride-free medium significantly reduced the DIDS-sensitive (36.31 versus 16.85
      pmol/mg protein for 4 minutes, P < .001) and furosemide-sensitive (34.72 versus
      8.78 pmol/mg protein for 4 minutes, P < .001) [14C]formate uptake. These results
      are compatible with the presence of chloride-formate exchange in VSMCs. Influx of
      [14C]formate into sarcolemmal vesicles isolated from canine heart was
      significantly higher in the presence of an outward chloride gradient than in its
      absence (18.1 +/- 2.3 versus 9.6 +/- 1.7 pmol/mg protein for 30 seconds, P <
      .03). The chloride-formate exchange was significantly inhibited in the presence
      of 1 mmol/L DIDS or furosemide (41% and 52%, respectively). We conclude that the
      distribution of chloride-formate exchange may be more universal than previously
      suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261595
TI  - A monoclonal antibody against rabbit tissue factor inhibits thrombus formation in
      stenotic injured rabbit carotid arteries.
AB  - Tissue factor (TF) is a transmembrane protein that binds factor VII/VIIa, thus
      activating the extrinsic blood coagulation pathway. Since this pathway appears to
      be involved in the formation of intravascular thrombi, the anti-rabbit TF
      monoclonal antibody, AP-1, was produced and tested as an antithrombotic agent in
      a rabbit model of recurrent intravascular thrombosis. In this model, a plastic
      constrictor is positioned around the injured rabbit carotid arteries, and flow is
      monitored with a Doppler flow probe. This produces cyclic flow variation (CFV) in
      the carotid artery, which is caused by recurrent formation and dislodgment of
      thrombi at the site of the stenosis. After monitoring CFV pattern for 30 minutes,
      AP-1 was infused intravenously into nine rabbits at doses of 0.05 to 1.5 mg/kg
      body weight, and a control monoclonal antibody that does not react with rabbit TF
      was infused into four additional rabbits. In all rabbits receiving AP-1, CFV was
      abolished, and a steady normal blood flow was restored, indicating that thrombus
      formation had been blocked by AP-1. By contrast, in all rabbits that received the
      control monoclonal antibody, CFV continued unaltered. There was no change in the
      partial thromboplastin time and ex vivo platelet aggregation to several different
      agonists after infusion of AP-1, indicating an absence of systemic effects on the
      coagulation process. We conclude that activation of the extrinsic coagulation
      pathway has a key role in triggering intravascular thrombosis and that an anti-TF
      monoclonal antibody is an effective antithrombotic agent that could have
      therapeutic potential for humans.

PMID- 8261596
TI  - Myocardial metabolism during increased work states in the porcine left ventricle
      in vivo.
AB  - It is not known whether myocardial energy requirements can be increased to the
      degree that they exceed myocardial O2 availability in the absence of
      abnormalities of coronary blood flow or coronary reserve. To determine whether
      this form of "demand ischemia" occurs, 10 swine were subjected to pressure
      overload induced by aortic constriction, inotropic and chronotropic stimulation
      by dobutamine, and the combination of these interventions. In an additional 9
      animals, intravenous adenosine was administered during the combination of
      constriction and dobutamine to determine whether further increases in coronary
      flow could be achieved and if they would attenuate the metabolic changes. Left
      ventricular anterior wall transmural blood flow was measured by radioactive
      microspheres. Energy phosphates were assessed by 31P magnetic resonance
      spectroscopy using the Fourier series window technique to increase the proportion
      of signal derived from the subendocardium. Myocardial lactate release was
      quantified independent of net lactate uptake using an isotopic tracer technique.
      The three interventions produced 39% to 195% increases in myocardial O2 uptake
      from control measurements. The phosphocreatine to ATP ratio (PCr/ATP),
      uncorrected for partial saturation, fell significantly, from 1.39 +/- 0.10 at
      control conditions to 1.25 +/- 0.10 with dobutamine alone and 1.15 +/- 0.08 with
      dobutamine plus constriction (P < .05 for both). Myocardial lactate release rose
      from 0.21 +/- 0.03 mumol.g-1.min-1 at control conditions to 0.45 +/- 0.05 and
      0.59 +/- 0.10 mumol.g-1.min-1, respectively (P < .05 for both), with these two
      interventions. Although transmurally averaged left ventricular blood flow rose
      from 0.97 +/- 0.09 mL.g-1.min-1 at control conditions to 3.25 +/- 0.47 mL.g-1.min
      1 (P < .001) and subendocardial blood flow increased from 1.02 +/- 0.09 to 2.92
      +/- 0.45 mL.g-1.min-1 (P < .001) at the highest of the three increased work
      states, the subendocardial to subepicardial flow ratio declined progressively
      from 1.13 +/- 0.08 to 0.87 +/- 0.04 (P < .05). With a further increase in aortic
      constriction, myocardial O2 uptake and subepicardial blood flow rose, whereas
      subendocardial blood flow did not change, and there was a further decline in
      PCr/ATP and a rise in lactate release. Although adenosine increased the average
      myocardial blood flow during high work state from 3.79 +/- 0.91 to 6.29 +/- 1.08
      mL.g-1.min-1 (P < .001), the further rise in subendocardial flow from 3.08 +/-
      0.62 to 3.78 +/- 0.68 mL.g-1.min-1 was not significant, nor were the accompanying
      changes in PCr/ATP or lactate metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8261597
TI  - Relative significance of endothelium and internal elastic lamina in regulating
      the entry of macromolecules into arteries in vivo.
AB  - A role for the internal elastic lamina (IEL), which separates the intima and
      media of an artery wall, as a restrictive barrier to macromolecular movement has
      been suggested in atherosclerotic lesion development or restenosis during
      angioplasty. The permeability coefficient of the IEL, however, has never been
      quantified in unperturbed vessels in vivo. Using a newly developed technique, we
      measured the concentration distributions in both intima and media of cationic (pI
      approximately 8.5) and anionic (pI approximately 6.3) isozymes of the 44-kD
      macromolecule horseradish peroxidase (HRP). Two mathematical models of arterial
      wall transport differing in their resolution of the intima were required to
      simulate the concentration distribution data and to estimate the parameters of
      interest. Optimal estimates of the permeability coefficients of the endothelium
      (PE) and IEL (PIEL) to HRP were determined by the best least-squares fit of the
      two models to experimental data. These estimates (anionic: PE = 0.050 +/- 0.021
      microns/min, PIEL = 0.146 +/- 0.082 microns/min, n = 8; cationic: PE = 0.034 +/-
      0.018 microns/min, PIEL = 0.110 +/- 0.047 microns/min, n = 8) indicate that the
      IEL is responsible for approximately 25% (anionic, 26 +/- 9%; cationic, 25 +/-
      13%) of the resistance to HRP transport from the blood into the arterial media.
      Although both parameters were less for the cationic preparation, the differences
      were not significant, and the relative role of the IEL was similar for both
      molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261598
TI  - Cellular uncoupling induced by accumulation of long-chain acylcarnitine during
      ischemia.
AB  - Long-chain acylcarnitines (LCACs) increase rapidly within minutes after the onset
      of ischemia in vivo or hypoxia in vitro and produce a time-dependent reversible
      reduction in gap junctional conductance in isolated myocyte pairs. The present
      study was performed to assess whether LCACs contribute to cellular uncoupling in
      response to ischemia in isolated blood-perfused rabbit papillary muscles by use
      of simultaneous measurements of transmembrane action potentials, extracellular
      electrograms, extracellular K+, and tissue LCACs and ATP. LCACs increased
      threefold in response to 20 minutes of no-flow ischemia from 127 +/- 5 to 397 +/-
      113 pmol/mg protein (P < .01), concomitant with the onset of cellular uncoupling,
      extracellular K+ accumulation, and a marked reduction in conduction velocity and
      action potential duration. To assess whether inhibition of the accumulation of
      LCACs modified the electrophysiological alterations during ischemia, muscles were
      pretreated with either sodium 2-(5-(4-chlorophenyl)-pentyl)-oxirane-2-carboxylate
      (POCA, 10 mumol/L) or oxfenicine (100 mumol/L), inhibitors of carnitine
      acyltransferase I. Both POCA and oxfenicine completely prevented the increase in
      LCACs even with 40 minutes of ischemia (138 +/- 37 and 56 +/- 4 pmol/mg protein,
      respectively), associated with a marked delay in the onset and progression of
      cellular uncoupling and ischemic contracture. Although POCA and oxfenicine did
      not affect either the initial early rise in extracellular K+ or the initial fall
      in conduction velocity, both agents markedly delayed the secondary rise in
      extracellular K+ as well as the secondary fall in conduction velocity,
      independent of the level of tissue ATP. Thus, LCACs accumulate during myocardial
      ischemia and contribute substantially to the initiation of cell-to-cell
      uncoupling. Inhibition of carnitine acyltransferase I and prevention of the
      increase in LCACs markedly delays cellular uncoupling and development of ischemic
      contracture in response to ischemia.

PMID- 8261599
TI  - Subcellular mechanism for Ca(2+)-dependent enhancement of delayed rectifier K+
      current in isolated membrane patches of guinea pig ventricular myocytes.
AB  - Intracellular Ca2+ augments delayed rectifier K+ current (IK) in cardiac
      myocytes, which may play a major modulatory role in repolarization of action
      potentials. We investigated subcellular mechanisms for Ca(2+)-induced enhancement
      of IK in large-pipette inside-out membrane patches excised from isolated guinea
      pig ventricular myocytes. When [Ca2+]i was raised from 10(-8) to 10(-6) mol/L,
      the amplitude of IK measured at +80 mV was increased from 12.0 +/- 2.2 to 19.5 +/
      3.3 pA (P < .01). The enhancement of IK by Ca2+ was dose dependent, with an EC50
      of 3.8 x 10(-8) mol/L. A calmodulin antagonist, W7 (50 mumol/L), calmidazolium
      (100 mumol/L), or HT-74 (20 mumol/L), added to the intracellular solution
      abolished enhancement of IK by Ca2+, whereas the inactive form of the W7
      analogue, W5, had no effect on IK. In the presence of a protein kinase inhibitor
      with a relatively high specificity for protein kinase C (H7), for protein kinase
      A (H8 or peptide-type inhibitor PKI), or for calmodulin kinase II (KN-62) or a
      nonspecific inhibitor of serine/threonine protein kinases (staurosporine),
      increases in [Ca2+]i still enhanced IK. Ca(2+)-induced enhancement of IK was also
      observed when Mg2+ and ATP were omitted from the intracellular solution to delete
      exogenous phosphate donors and when adenylylimidodiphosphate was added to
      preclude trapped cytoplasmic substrates. Thus, cardiac IK was enhanced by
      increases in [Ca2+]i at a physiological range via a calmodulin-dependent pathway,
      which did not involve a phosphorylation process.

PMID- 8261600
TI  - Ophthalmologists: the voice of eye care.

PMID- 8261601
TI  - Micropachometry.

PMID- 8261602
TI  - Risk factors with contact lens related suppurative keratitis.
AB  - Risk factors in contact lens related suppurative keratitis were investigated.
      Over 12 months, sixty contact lens wearers presented with presumed microbial
      keratitis and 147 presented with presumed sterile keratitis. The control group
      consisted of contact lens wearers without lens related disorders (n = 507). The
      relative risk of microbial keratitis for extended wear soft contact lens users
      were 36.8 times (12.6-107.6) that of rigid gas permeable (RGP) contact lens
      users; while the relative risk of sterile keratitis among extended wear soft lens
      users was 4.6 times (2.2-9.9) that of RGP lens users. For daily wear soft contact
      lens users, the relative risk of microbial keratitis was 4.2 times (1.1-16.0)
      that of RGP lens wearers; for sterile keratitis the relative risk was 2.3 times
      (1.3-4.3) greater than RGP contact lens users. A multivariable logistic
      regression analysis was used to examine associated risk factors for daily and
      extended wear soft lens users. The type of disinfection system and its frequency
      of use were associated with both microbial keratitis and sterile keratitis in
      daily wear users. Duration of overnight wear and gender were associated with
      microbial keratitis, while a patient's age and socioeconomic class were
      associated with sterile keratitis. Different relative risks and risk factors for
      microbial keratitis and sterile keratitis support the use of a clinical
      definition to differentiate the diseases.

PMID- 8261603
TI  - Epithelial, stromal, and endothelial responses to hydrogel extended wear.
AB  - Corneal epithelial, stromal, and endothelial edema were assessed in 19 subjects
      before and after a 4-month period of hydrogel contact lens extended wear. A thick
      hydrogel lens was worn under closed-eye conditions for 3 hours to induce stromal
      edema and endothelial edema (blebs), and eye bathing with a hypotonic solution
      was used to induce epithelial edema. Initial central stromal edema (corneal
      thickness) was 14.4 +/- 0.6% in response to the stress lens compared with 2.1 +/-
      0.4% in the control eye (mean +/- SE). After 4 months of lens extended wear,
      stromal edema was significantly reduced (P < 0.0001) to 12.3 +/- 0.6% and 0.5 +/-
      0.2% in test and control eyes, respectively. Adjustment of the stromal edema
      response at the second visit for residual edema from the extended wear accounted
      for some of the reduction, but the edema response remained significantly
      decreased (stress lens: 13.6 +/- 0.7%; and control eye: 1.2 +/- 0.4%).
      Endothelial edema response to the stress lens, as measured on a scale of 1 to 7,
      decreased from 4.6 +/- 0.3 to 2.8 +/- 0.3 over the period of extended wear. The
      final level was indistinguishable from that of the eye not wearing the stress
      lens. The epithelial edema response to hypotonic exposure was not altered with
      extended wear. These findings indicate that the stromal and endothelial edema
      responses may be unreliable diagnostic signs of the physiologic impact of
      hydrogel extended wear.

PMID- 8261604
TI  - Effect of contact lens wear on photorefractive keratectomy.
AB  - This study compares refractive effect and epithelial healing after
      photorefractive keratectomy among patients who wore contact lenses before surgery
      versus those who wore glasses before surgery. Data were reviewed on 130
      photorefractive keratectomy cases at the 1-week, 2-week, and 4- to 6-month
      postoperative visits. The patients were divided into three groups based on
      whether or not they wore contact lenses before surgery: 1) rigid gas permeable
      lens wearers; 2) soft lens wearers; 3) no contact lens wear. There were no
      significant differences in epithelial healing among the groups. Some regression
      of refractive effect was observed both in mean spherical equivalent and in mean
      keratometry in all the groups from 2 weeks to 6 months postoperatively. There was
      no significant difference in the regression of each group. In addition, the
      changes of spherical equivalent and keratometry before surgery and 4 to 6 months
      after surgery were compared among the groups with no significant differences.
      Based upon these results, we conclude that contact lens wearing does not seem to
      influence epithelial healing after photorefractive keratectomy surgery and also
      does not affect the refractive effect in the early postoperative period.

PMID- 8261605
TI  - Clinical evaluation of the anterior constant focus (ACF) annular bifocal contact
      lens.
AB  - We evaluated the distance and near vision of 33 presbyopic patients who wore the
      Anterior Constant Focus (ACF) rigid gas permeable (RGP) bifocal lens. Twenty
      seven patients (82%) wore the lenses for one year; the six patients who quit the
      study complained of unacceptable vision (four patients) and discomfort (two
      patients). Twenty-five patients (76%) obtained 20/25 or better distance vision,
      and 28 patients (85%) obtained J2 or better near vision. Contrast sensitivity was
      within normal limits in 24 of 33 (73%) patients. We feel the ACF lens provides
      good bifocal vision in a non-translating RGP design.

PMID- 8261606
TI  - Areal differences in oxygen supply to a cornea wearing an optically powered
      hydrogel contact lens.
AB  - If there is little lateral diffusion of oxygen in an optically powered hydrogel
      contact lens, then point-to-point differences in the thickness of the lens can
      result in different areas of the cornea receiving different amounts of oxygen.
      Specifically, areas under the thicker portions of the lens will receive less
      oxygen. Cells in these oxygen-deprived areas may produce metabolic products that
      spread laterally in the cornea resulting in cornea-wide edema. The fact that most
      of a contact lens transmits adequate oxygen to the cornea does not lead to
      satisfactory lens performance, if some part of the lens is too thick. We address
      the problem of lateral diffusion of oxygen in a contact lens and describe the
      methods for quantifying the point-to-point thickness of optically powered
      hydrogel lenses. Areal differences in oxygen supply to the cornea are found to be
      almost totally dependent on optical power; water content and lens design have far
      less effect.

PMID- 8261607
TI  - Excimer laser phototherapeutic keratectomy.
AB  - The argon-fluoride 193 nm excimer laser is currently under investigation in the
      United States for both refractive and therapeutic indications. We report the
      preliminary results of phototherapeutic keratectomy in 15 patients. Patients were
      divided as follows: group 1 (11 patients with anterior corneal pathology) and
      group 2 (four patients with refractive error after ocular surgery). Mean follow
      up was 4.7 and 4.0 months in the two groups, respectively. Although results in
      group 1 are difficult to quantify because of varied indications, visual acuity
      improved in six of 11 patients (55%) and remained the same in five patients
      (45%). In group 2 uncorrected visual acuity improved in two patients (50%) and
      remained the same in two patients. Best corrected vision was the same or better
      in three patients but decreased four lines in one patient at 1-month follow-up,
      possibly related to retinal pathology. Overall, the results of excimer laser
      phototherapeutic keratectomy are quite promising, especially in light of
      alternative treatments that are more invasive.

PMID- 8261608
TI  - The epidemiology of contact lens related diseases in the United Kingdom.
AB  - This review evaluates the epidemiologic methods used to study contact lens
      related diseases in the United Kingdom. The results of these studies are compared
      to major US studies. The advantages and limitations of various epidemiologic
      study designs are discussed. The role of noncomparative cohort studies,
      particularly premarket studies, in underestimating lens related disease is
      examined. Descriptive studies and the difficulties related to their
      interpretation are also described. The use of case control studies for
      investigating both the risks and causes of lens related diseases is evaluated and
      compared to the cohort study design. The results of these studies in the
      investigation of the complications of contact lens wear, including keratitis, are
      summarized. Finally, the relevance of these findings to contact lens wearers and
      practitioners is explored.

PMID- 8261609
TI  - A central nervous system keratan sulfate proteoglycan: localization to boundaries
      in the neonatal rat brain.
AB  - During the development of the central nervous system (CNS), adhesive molecules
      promote the formation of axonal pathways and appropriate neuronal connections by
      facilitating cellular interactions. In addition to the interactions that bring
      neurons together, recent evidence suggests inhibition of neuronal interactions
      also plays a role by restricting axons to their appropriate pathways and forming
      boundaries between functional units of the developing CNS. The present study
      describes the distribution of a recently identified large keratan sulfate
      proteoglycan, ABAKAN, in the postnatal day 14 (P14) and adult rat brain. In the
      adult brain ABAKAN appears to be relatively evenly distributed throughout the
      CNS, while at P14 this proteoglycan is found at high concentrations between
      different functional units of the neonatal brain. For example, ABAKAN appears to
      separate different cortical areas and mark the boundaries between thalamic
      nuclei. In vitro assays demonstrate that this keratan sulfate proteoglycan is a
      potent inhibitor of neurite growth. The distribution of ABAKAN at P14 and the
      effects of this keratan sulfate proteoglycan on neurite growth suggest that
      ABAKAN functions as a molecular barrier to axonal growth in the developing rat
      brain.

PMID- 8261610
TI  - Maternal regulation of the hypothalamic-pituitary-adrenal axis in the infant rat:
      the roles of feeding and stroking.
AB  - Twenty-four hours of maternal separation results in increased secretion of ACTH
      and corticosterone (CORT), suggesting the hypothalamic-pituitary-adrenal (HPA)
      axis is regulated by some aspect of maternal behavior. Previous results indicate
      that feeding plays a role in maintaining low levels of CORT in 12-day-old pups.
      In Experiment 1 basal and stress levels of CORT and ACTH were measured in
      maternally-deprived pups either provided or not with milk to determine whether:
      (1) feeding maintains ACTH secretion at low levels, and/or (2) feeding maintains
      the adrenal insensitive to ACTH. The results showed that, although ACTH levels
      were markedly low (compared to previous values reported by this laboratory) for
      both groups, only non-fed pups showed a robust increase in basal and stress CORT
      levels. During the deprivation period in Experiment 1, all pups were manually
      stroked to induce urination and defecation, suggesting an effect of stroking on
      ACTH secretion. Experiment 2 examined this hypothesis. Stroking suppressed stress
      induced elevations of ACTH secretion due to maternal deprivation. CORT levels,
      however, were elevated in all deprived pups. The results indicate that maternal
      regulation of the infant's HPA axis occurs at multiple levels. Feeding appears to
      regulate adrenal sensitivity, whereas anogenital stroking inhibits the activation
      of centrally-controlled components of the axis.

PMID- 8261611
TI  - Accumulation of theophylline, theobromine and paraxanthine in the fetal rat brain
      following a single oral dose of caffeine.
AB  - This paper describes the disposition of caffeine and its metabolites,
      theophylline, theobromine and paraxanthine in the 20-day fetal and adult brains
      following a single maternal dose of 5 or 25 mg/kg caffeine. Brains and plasma
      were collected 5 and 30 min, and 1, 3, 8 and 24 h after dosing. It was found that
      fetal and adult caffeine AUC (area under the concentration-time curve) values did
      not differ between the brain and plasma at either dose. Caffeine's primary
      metabolites theophylline, theobromine and paraxanthine did, however, accumulate
      in the fetal brain at both doses resulting in a 3-fold increase in brain
      metabolite exposure compared to fetal circulatory levels. In contrast to the
      fetus, metabolite AUC values after a dose of 25 mg/kg were found to be lower in
      the brains of adults compared with plasma. This suggests that caffeine's primary
      metabolites might be selectively excluded from the adult brain. In conclusion we
      have shown that, unlike the adult, the fetal rat brain accumulates theophylline,
      theobromine and paraxanthine when exposed to caffeine doses comparable to those
      attainable by normal human consumption. Since many aspects of caffeine metabolism
      are similar in the rat and human, we suggested that particular attention should
      be paid to the consumption of caffeine during pregnancy.

PMID- 8261612
TI  - Midkine that promotes survival of fetal human neurons is produced by fetal human
      astrocytes in culture.
AB  - Midkine (MK), a retinoic acid responsive gene product, is a novel heparin-binding
      growth factor with an apparent molecular weight of 14-kDa. In fetal human neuron
      cultures, addition of recombinant human MK (10-100 ng/ml) resulted in a 3-fold
      increase in the number of surviving neurons under the serum-free culture
      condition. Production of MK was identified in the conditioned medium of astrocyte
      enriched cultures by immunoblotting but not in the medium of neuron-enriched
      cultures. The level of MK production was not affected by treatment with retinoic
      acid. These results indicate that in the developing human central nervous system,
      astrocytes secrete MK that exhibits potent trophic activity to neurons.

PMID- 8261613
TI  - Neonatal exposure to D,L-2-amino-3-phosphonopropionate (D,L-AP3) produces lesions
      in the eye and optic nerve of adult rats.
AB  - Metabotropic glutamate receptors are a recently described receptor class with
      emerging importance in synaptic plasticity and brain development. Activation of
      metabotropic glutamate receptors results in several cellular secondary messenger
      events that are especially important during postnatal development. This study
      characterized the effects of D,L-2-amino-3-phosphonopropionate (D,L-AP3), an
      aspartic acid analog with agonist and antagonist activity at the metabotropic
      receptor, on the postnatal development of the rat eye and optic nerve. Sprague
      Dawley rat pups were treated daily (i.p.) with saline or 500 mg/kg D,L-AP3 on
      postnatal days (PND) 4-10 or 10-14. After making clinical and ophthalmoscopic
      examinations, rats were necropsied between 65 and 70 days of age and light
      microscopic evaluations were made of eyes and optic nerves. Between postnatal
      days 10-20, all treated rats exhibited motor tremors, circling, and head tilt.
      Ophthalmoscopic lesions were more severe in rats treated on days 4-10 than days
      10-14 and included decreased retinal vasculature, cataracts, and retinal
      dysplasia, hypoplasia, and detachment. All rats treated on days 4-10 had severe
      optic nerve atrophy/hypoplasia grossly and severe retinal atrophy, retinal
      detachment, and cataracts histologically. Seven of eight rats treated on days 10
      14 had qualitatively similar but less severe lesions. Overall, rats treated with
      D,L-AP3 on PND 4-10 had earlier and more severe retinal and optic nerve lesions
      when compared to rats treated on PND 10-14. These data characterize the
      morphologic effects in adult rats exposed to D,L-AP3 as neonates and suggest a
      possible role for the metabotropic receptor in the postnatal development of
      retina and optic nerve.

PMID- 8261614
TI  - Molecular cloning and cellular localization of trkC in the chicken embryo.
AB  - Degenerate primers directed against conserved regions of the trk and trkB amino
      acid sequences were used in the polymerase chain reaction to isolate a 455 bp
      fragment from embryonic day 3 chicken cDNA encoding the trkC. This fragment was
      subsequently used to synthesize an anti-sense trkC cRNA probe which was used in a
      RNase protection assay of total RNA from chicken embryos. trkC mRNA was found in
      the E2 embryo with increasing levels later in development. In the E9 embryo
      highest levels were found in brain and spinal cord with intermediate levels in
      eye, heart, gut and muscle. Low levels were found in kidney, liver, skin and yolk
      sac. Using the 455 bp trkC fragment as a probe in RNA blot analyses of poly A+
      RNA, a major transcript of 6.3 kb and two minor transcripts of 3 kb and 10 kb
      were found. In situ hybridization was performed on embryos taken at three stages
      of development (embryonic day 3, 9 and 19), using a 48-mer antisense
      oligonucleotide probe for chicken trkC. Within the sensory nervous system trkC
      mRNA expression at all ages was confined to the ventrolateral neurons of the
      spinal sensory and trigeminal ganglia as well as distal ganglia associated with
      the VIIth, IXth and Xth cranial nerves. Labelling for trkC mRNA was also observed
      within the developing CNS at E3 and the ganglion of Remak at E19. A barely
      detectable level of expression was observed in the sympathetic chain and no
      labelling was evident in the proximal ganglia of the cranial nerves. These
      results suggest that neurons have a very early capacity to respond to
      neurotrophin-3 which continues throughout embryonic development. The early
      expression of trkC mRNA also support the growing evidence suggesting a role for
      neurotrophins in neuronal differentiation.

PMID- 8261615
TI  - Stimulation of D-aspartate efflux by mercuric chloride from rat primary astrocyte
      cultures.
AB  - Mercuric chloride (HgCl2; MC) was shown to increase D-aspartate release from
      preloaded astrocytes in a dose-dependent fashion. Two sulfhydryl (-SH) protecting
      agents, a cell membrane non-penetrating compound, reduced glutathione (GSH), and
      the membrane-permeable dithiothreitol (DTT), were found to inhibit the
      stimulatory action of MC on the efflux of radiolabeled D-aspartate. MC-induced D
      aspartate release was completely inhibited by the addition of 1 mM DTT or GSH
      during the actual 5 min perfusion period with MC (5 microM). However, when added
      after MC treatment, this inhibition could not be sustained by GSH, while DTT
      fully inhibited the MC-induced release of D-aspartate. Neither DTT nor GSH alone
      had any effect on the rate of astrocytic D-aspartate release. Accordingly, it is
      postulated that the stimulatory effect exerted by MC on astrocytic D-aspartate
      release is associated with vulnerable -SH groups located within, but not on the
      surface of the cell membrane. Omission of Na+ from the perfusion solution did not
      accelerate MC-induced D-aspartate release, suggesting that reversal of the D
      aspartate carrier can not be invoked to explain MC-induced D-aspartate release.
      Furthermore, MC did not appear to be associated with astrocytic swelling.

PMID- 8261616
TI  - Neovascularization and the appearance of morphological characteristics of the
      blood-brain barrier in the embryonic mouse central nervous system.
AB  - Vascularization and expression of blood-brain barrier (bbb)-associated
      morphological characteristics during the embryonic development of the mouse
      central nervous system (CNS) was studied by ultrastructural analysis. At
      embryonic day 9 (E9) capillaries were only found in the perineural mesenchymal
      tissue. These capillaries showed fenestrations, and pericyte like cells (PC) were
      found joined to the vessel walls. Around E10 endothelial cells (EC) together with
      PC started invading the intraneural section. At this stage, the immigrating
      endothelial cells lost their fenestrations and exhibited numerous, partly
      extended junctional complexes, which appeared 'tight' in some places. A first
      intraneural anastomotic plexus was observed at E10, as evidenced by the presence
      of blood cells in all capillary lumens. While the number of junctional complexes
      remained constant in intraneural capillaries, the frequency of pinocytotic
      vesicles decreased significantly from E10 to E17. These findings 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- 8261617
TI  - Effects of estradiol on the development of sexual dimorphism in the bed nucleus
      of the accessory olfactory tract in the rat.
AB  - Orchidectomized males injected with a single dose of estradiol benzoate (EB) on
      the day of birth (D1) showed a volume and neuron number in the nucleus of the
      accessory olfactory tract (BAOT) similar to that of control males. However,
      orchidectomized males and those orchidectomized and given a single dose of DHT on
      D1 showed a decrease in BAOT volume and neuron number with respect to control
      males. These results support the notion that estradiol induces the morphological
      masculinization of this structure. The inability of DHT in counteracting the
      effect of orchidectomy is addressed taking into account the inhibitory action of
      androgens.

PMID- 8261618
TI  - Identification of a population of amacrine cells rich in insulin receptors.
AB  - Insulin receptor immunoreactivity in the developing chick retina was examined by
      immunocytochemistry. Insulin receptor immunoreactivity could be detected
      throughout the retina at all stages studied. Beginning at E12, a limited number
      of amacrine cells located in the inner level of the inner nuclear layer were
      strongly immunoreactive. By E19 there was a decrease in immunoreactivity
      throughout the retina, with the exception of the ganglion cell layer and a few
      amacrine cells and their process; this distribution was present in 3-day-old
      posthatched chick retina. The pattern of immunoreactivity of insulin receptors
      may indicate a unique role for insulin in the development and physiology of some
      amacrine cells.

PMID- 8261619
TI  - The expression of a novel receptor-type tyrosine phosphatase suggests a role in
      morphogenesis and plasticity of the nervous system.
AB  - Analysis of the localization of receptor-type protein tyrosine phosphatase-beta
      (RPTP-beta) by in situ hybridization and immunocytochemistry indicates that it is
      predominantly expressed in the developing central nervous system (CNS). RPTP-beta
      is highly expressed in radial glia and other forms of glial cells that play an
      important role during development. The immunoreactivity localizes to the radial
      processes of these cells, which act as guides during neuronal migration and
      axonal elongation. The pattern of RPTP-beta expression changes with the
      progression of glial cell differentiation. In the adult, high levels of RPTP-beta
      are seen in regions of the brain where there is continued neurogenesis and
      neurite outgrowth. The spatial and temporal patterns of RPTP-beta expression
      suggest that this receptor phosphatase plays a role in morphogenesis and
      plasticity of the nervous system.

PMID- 8261620
TI  - In vitro degradation of very low density lipoprotein from diabetic patients by
      lipoprotein lipase.
AB  - Fatty acid release by incubation with lipoprotein lipase (LPL) in vitro from very
      low density lipoproteins (VLDL) obtained from diabetic patients was low compared
      with that from healthy subjects, though the compositions were similar in both
      VLDL. Percentages of the large size VLDL decreased and those of the small size
      VLDL increased after the incubation with LPL. At the same time, on polyacrylamide
      gel disk electrophoresis, the smaller catabolic products from these VLDL appeared
      at a similar position to that of low density lipoproteins (LDL) and at the
      running front where high density lipoproteins (HDL) had migrated. The amount of
      the small size VLDL and the LDL-like lipoproteins produced from diabetic VLDL
      were less than those from normal VLDL and inversely correlated with the percent
      decrease of the large original size VLDL. This fact suggests that VLDL from
      diabetic patients are poor substrates for LPL compared with normal VLDL.

PMID- 8261621
TI  - Increased fragmentation of urinary fibronectin in cancer patients detected by
      immunoenzymometric assay using domain-specific monoclonal antibodies.
AB  - Monoclonal antibodies (MoAbs) recognizing the distinct domains of human
      fibronectin had previously been established and they were used to construct
      several sandwich immunoenzymometric assays (IEMAs) for the structural analysis of
      fibronectin found in the urine of cancer patients. Urinary fibronectin (UFN) was
      immunodetectable only with FN12-8 and FN30-8 MoAbs against cell-binding domains
      and was less reactive with other IEMAs using MoAbs directed to terminal domains,
      indicating that UFN was almost completely fragmented and consisted mainly of cell
      binding regions. The IEMA using MoAbs against cell-binding domains had sufficient
      immunoreactivities with the antigen fragmented by artificial proteolysis, but
      these fragments could hardly be detected by other IEMAs. UFN levels were
      significantly elevated in various cancer patients and extremely elevated in some
      patients with distant metastasis. It is presumed that UFN fragments which
      increase in cancer patients are generated by extracellular matrix destruction.
      Thus UFN levels and the ratio of the fragmented UFN level to the non-fragmented
      UFN level appear to be informative clinical indicators of tumor malignancy or
      metastatic ability in cancer patients.

PMID- 8261622
TI  - Demonstration of immunoglobulin G with affinity for dopamine in cerebrospinal
      fluid from psychotic patients.
AB  - Using an enzyme-linked immunosorbent assay, significantly raised concentrations
      of immunoglobulin G with affinity for the neurotransmitter dopamine were
      demonstrated in cerebrospinal fluid from psychotic patients. We have varied the
      antigen presentation in order to find a conjugate with low unspecific binding.
      The conjugation of dopamine to carbodiimide-activated poly-L-glutamic acid and
      that to activated succinimide ester of biotin are described. The use of
      glutaraldehyde conjugation is not recommended because of the risk of formation of
      tetrahydroisoquinolines. A strong correlation (r = 0.94, P < 0.001) between the
      results obtained with dopamine conjugated to poly-L-glutamic acid and dopamine
      conjugated to biotin was observed. Forty-two human cerebrospinal fluid samples
      from 20 psychotic patients, (12 with a bipolar disorder and 8 with schizophrenia)
      and 22 control patients, with various neurological diseases but no apparent
      psychiatric diseases were investigated. A significantly higher incidence (P <
      0.001) of antibodies with affinity for dopamine were found in the group of
      psychotic patients compared with the neurological control group.

PMID- 8261623
TI  - Comparison of a mechanized version of the 'Konig' reaction and a fluorescence
      polarization immunoassay for the determination of nicotine metabolites in urine.
AB  - Smoking can be detected by the determination of cotinine in urine. We compared
      the performance of an automated modification of the 'Konig' reaction adapted to a
      centrifugal analyzer with an automated commercial fluorescence polarization
      immunoassay (TDX system). In the latter assay, cotinine, as the primary
      metabolite of nicotine, can be measured with high specificity. In contrast, the
      'Konig' reaction also detects nicotine metabolites other than cotinine by a group
      colour reaction. Analysis speed of the 'Konig' reaction was about 66 samples/h
      with a detection limit 2 S.D. above the mean value of urine samples of non
      smokers. Analysis speed of the TDX system was 41 samples/h. The coefficient of
      variation (C.V.) of both methods in smokers' urine was 8.6% ('Konig' reaction)
      vs. 3.4% (TDX system) in the high range and 16.4% vs. 9.5% in the low range. In a
      controlled, prospective study recruiting 86 cigarette-smoking volunteers, 83.7%
      were correctly classified as being smokers by both systems, 13.9% were classified
      as smokers by the 'Konig' reaction only and 2.4% were misclassified as non
      smokers by both systems. Thus, the sensitivity of the 'Konig' reaction seems to
      be higher than in the TDX system (97.6% vs. 83.7%). Of 33 non-smoking
      individuals, 81.8% were correctly classified as non-smokers by both systems, 18.2
      were misclassified as smokers by the 'Konig' reaction and no person was
      misclassified by the fluorescence polarization immunoassay. Thus, the specificity
      of the TDX system seems to be higher than that of the 'Konig' reaction (100% vs.
      81.8%). We conclude that both systems are applicable to detect individuals who
      smoke regularly by simple urine testing. The higher specificity of the TDX system
      is outweighed by the higher sensitivity of the 'Konig' reaction at much lower
      cost.

PMID- 8261624
TI  - Value of faecal alpha-1-antitrypsin, haemoglobin and a chemical occult blood test
      in the detection of gastrointestinal disease.
AB  - Specimens from hospital out-patients and in-patients sent for faecal occult blood
      tests were also analysed for faecal alpha-1-antitrypsin and faecal haemoglobin.
      453 stool specimens from 222 patients were analysed. The clinicians were only
      aware of the faecal occult blood test results, and diagnoses were made using
      conventional clinical and investigative criteria. Gastrointestinal bleeding or
      putative sites of bleeding were diagnosed in 98 patients, whereas in 81 patients
      putative sites of bleeding were not found or other cause of anaemia diagnosed. In
      41 patients there was insufficient information to reach a definitive diagnosis.
      Comparison of the 3 faecal tests using these grouping methods showed that faecal
      alpha-1-antitrypsin performed best, with an accuracy of 89%, specificity of 90%
      and sensitivity of 88%, all significantly better (P < 0.001) than the faecal
      occult blood test (68%, 60% and 73%, respectively). There was no significant
      difference between the performance of the faecal occult blood and faecal
      haemoglobin tests. Faecal alpha-1-antitrypsin measurement may be a useful
      investigation in situations where a faecal occult blood test would normally be
      requested.

PMID- 8261625
TI  - Ascorbate concentration in human cerebrospinal fluid (CSF) and serum. Intrathecal
      accumulation and CSF flow rate.
AB  - Concentrations of ascorbate (vitamin C) in cerebrospinal fluid (CSF) from human
      controls (median 163 mumol/l, n = 63) were found to be in the same range as CSF
      samples from patients (n = 56) with various neurological diseases, but excluding
      those with blood-CSF barrier dysfunction. The CSF/serum concentration ratio in
      the former group is non-linear, decreasing with increasing serum concentration.
      Surprisingly, ascorbate concentration in blood (median 41 mumol/l, n = 119) was
      decreased significantly in cases of neurological diseases with a blood-CSF
      barrier dysfunction (median 26 mumol/l, n = 30). In this latter group a linear
      CSF to serum ratio with a mean of 5.7:1 (with CSF/serum albumin quotients QAlb =
      7.8-70.8 x 10(-3), median 10.0 x 10(-3)) was observed, approaching a value >
      12.5:1 in the case of complete stop of CSF flow. Serum ascorbate concentrations
      decreased with decreasing CSF flow rate (1 square root of QAlb), indicating a CSF
      flow-dependent constant contribution from high intrathecal ascorbate
      concentration to the varying diet-dependent concentrations in blood. In the
      control group the biological coefficient of variation for CSF ascorbate
      concentrations (C.V. = 21.1%) was smaller than for serum concentrations (C.V. =
      42.6%), confirming an efficient ascorbate homeostasis in human brain. This was
      different from uric acid which was used as a reference molecule with an inversed
      gradient in the same group of control patients. Similar variations in CSF(y) and
      serum(x) for urate concentrations are observed due to the strong correlation y =
      0.1x +/- 10 mumol/l, including 99% of the cases with an urate serum concentration
      range from 80 mumol/l to 460 mumol/l.

PMID- 8261626
TI  - Semi-automatic method for determination of different isoforms of carbohydrate
      deficient transferrin.
AB  - Carbohydrate deficient transferrin (CDT) has been reported to be one of the best
      biochemical markers of alcohol abuse. However, a need still exists for a simple
      and practical method for widespread laboratory use. A semi-automatic (SA)
      isoelectric focusing (IEF) assay for CDT (SA-IEF-CDT) by a Phast System is
      introduced here. Different isoforms of transferrin were separated by IEF on
      polyacrylamide gels (pI 4.0-6.5) and located by immunofixation with an anti
      transferrin serum. The precipitation bands were stained with Coomassie Brilliant
      Blue and quantitated densitometrically. The present method gave a picture of the
      relative amounts of 10 different transferrin isoforms. The percentage of CDT with
      pI > or = 5.7 (representing di-, mono- and asialotransferrin) was calculated. For
      comparisons transferrin bands with pI > or = 5.6 (tri-, di-, mono-, and
      asialotransferrin), pI > or = 5.8 (mono- and asialotransferrin) and pI > or = 5.9
      (asialotransferrin) as well as GGT, ASAT and ALAT were calculated. The method
      showed good linearity and it identified different isoforms in concentrations of <
      10 mg/l of transferrin. The correlation of the present method with a commercially
      available method employing anion exchange followed by double antibody RIA (AE-RIA
      CDT) was good (n = 38, r = 0.924). In 19/20 (95%) of healthy controls, the CDT
      value was below 4.4% (mean + 2 S.D.) of total transferrin, while higher values
      were observed in all 20 (100%) alcoholics. In conclusion, the developed semi
      automatic method is a practical and reliable alternative for determination of
      different transferrin isoforms.

PMID- 8261627
TI  - Inactivation of glutathione peroxidase following entrapment of purified alpha or
      beta hemoglobin chains in human erythrocytes.
AB  - Inactivation of glutathione peroxidase correlates with the rate of hemoglobin
      chain oxidation. The enzyme inactivation is mainly present in those conditions
      where the autoxidation of the oxygenated chains is followed by transformation of
      the oxidized molecule into a hemichrome. Free hemoglobin chains have been
      encapsulated in human red blood cells by a dialysis technique that involves
      transient hypotonic hemolysis followed by isotonic resealing. Chain-loaded
      erythrocytes represent a good in vitro model of thalassemia. The presence of free
      human chains in the cell alters the intraerythrocytic glutathione peroxidase
      activity (alpha chains are more effective in the inactivation of the enzyme with
      respect to the beta chains).

PMID- 8261628
TI  - The preferential site of non-enzymatic glycation of human apolipoprotein A-I in
      vivo.

PMID- 8261629
TI  - A study of growth factors in human renal cysts with or without renal cell
      carcinoma.

PMID- 8261630
TI  - Cyclooxygenase pathway in dermal fibroblasts from patients with metabolic
      disorders of peroxisomal origin.
AB  - Cyclooxygenase metabolism was studied in fibroblasts from patients with metabolic
      disorders of peroxisomal origin (adrenomyeloneuropathy, X-linked
      adrenoleukodystrophy, cerebrohepatorenal syndrome of Zellweger and rhizomelic
      chondrodysplasia punctata). In response to arachidonic acid (6.25-100 microM) or
      calcium ionophore A23187 (2.5-20 microM) prostaglandin E2 and 6-keto
      prostaglandin F1 alpha are the main cyclooxygenase metabolites formed. No
      formation of thromboxane B2 or 2,3-dinor-thromboxane B2 was found. Apparently due
      to the heterogeneous nature of peroxisomal disorders no uniform pattern of
      cyclooxygenase metabolism and eicosanoid concentrations in cell lines from
      patients with peroxisomal defects was found.

PMID- 8261631
TI  - Bile acid metabolism in three patients with mevalonic aciduria due to mevalonate
      kinase deficiency.

PMID- 8261632
TI  - Urinary excretion patterns of modified nucleosides, pseudouridine and 1
      methyladenosine, in healthy individuals.

PMID- 8261633
TI  - Fab treatment in acute digitalis intoxication: reliability of serum digoxin
      determination with the Stratus system.

PMID- 8261634
TI  - A rare case of IgD gammopathy associated with free light-chain cryoglobulinemia
      and a gelling Bence Jones protein.

PMID- 8261635
TI  - Abnormal serum lipid levels in subjects with gastric xanthoma.

PMID- 8261637
TI  - Serial brainstem auditory evoked responses in infants and children with AIDS.
AB  - Fourteen infants and children with AIDS had serial BAER studies, with stimuli
      delivered at a frequency of 10 and 50 per second. The latencies of waves I, III,
      V and interpeak latencies I-III, III-V and I-V were measured, and their changes
      over time were calculated. A significant correlation was found between wave V
      latency and I-V interval on the left, obtained with a stimulation rate of
      50/second, and the length of the follow-up period. There was a trend toward
      latency increases over time in 9 of the 14 patients. Two patients who had an
      increase of all wave latencies over time had the worst neurological involvement
      of all patients. There was no clear correlation between decrease of CD4/CD8
      lymphocytes subset ratio and increase of BAER latencies. We conclude that serial
      BAER studies may be useful in the following of the progression of central nervous
      system involvement in infants and children with AIDS.

PMID- 8261636
TI  - Vestibular evaluation--electronystagmography, rotational testing, and
      posturography.
AB  - This report describes a battery of tests that is utilized by several clinical
      laboratories to investigate vestibular and balance function. The
      electronystagmogram evaluates eye movements, inner ear function, brainstem
      function and cerebellar function. Sinusoidal vertical axis rotation is a
      sensitive measure of horizontal semicircular canal function that is often
      complimentary to the caloric stimulation portion of the electronystagmogram.
      Visual-vestibular interaction rotation testing is designed to evaluate brainstem,
      cerebellar and oculomotor function. Dynamic posturography facilitates measurement
      of standing balance and permits a quantification of the role of proprioception,
      vision and the vestibular system in the maintenance of standing balance.

PMID- 8261638
TI  - Persistent synchronous periodic discharges caused by anoxic encephalopathy due to
      cardiopulmonary arrest.
AB  - We report a patient with vegetative state induced by anoxic encephalopathy due to
      cardiopulmonary arrest who showed synchronous periodic discharges for a prolonged
      period. The patient was a 47-year-old man admitted to our hospital for
      depression, who suddenly developed cardiopulmonary arrest of unknown etiology,
      and entered chronic vegetative state as a result of anoxic encephalopathy.
      Electroencephalography (EEG) revealed that synchronous periodic discharges were
      present for up to 5 months. The wave pattern, periodicity and duration of
      appearance of synchronous periodic discharges were similar to those of
      synchronous periodic discharges in Creutzfeldt-Jakob disease (CJD). The
      periodicity of synchronous periodic discharges was gradually prolonged, with the
      course again similar to the discharges in CJD. The mechanism of occurrence is
      considered to be similar to that of synchronous periodic discharges in CJD.

PMID- 8261639
TI  - An unusual paroxysmal EEG pattern in mixed focal/generalized epilepsies.
AB  - This report focuses on an unusual paroxysmal discharge: "compounded sharp waves,"
      focal and mostly over frontotemporal regions, of high voltage, occurring mainly
      in sleep tracings of children with epileptic seizures. The duration of compounded
      sharp waves exceeds by far the maximum duration of classical sharp waves. In all
      of the three reported cases, there were also generalized-synchronous paroxysmal
      bursts and two children had spike-wave absences. The clinical significance of the
      focal discharge (in association with generalized bursts) remains unclear.

PMID- 8261640
TI  - The prognostic significance of diazepam-induced EEG changes in epilepsy: a follow
      up study.
AB  - Diazepam (0.1-0.3 mg/kg) was injected intravenously, its effect on scalp EEG was
      evaluated visually and by computer in 84 cases of epilepsy, and long-term follow
      up was carried out in an attempt to explore relationships between the EEG changes
      produced by diazepam and the prognosis in these patients. The average length of
      follow-up was 3 years (range 2-3.5) in 48 out of 84 cases (57%). The EEG visually
      responded to diazepam (abolition of abnormal activity with emergence of fast
      activity) in 33/48 cases. Subsequent follow-up showed that 29 (88%) of these had
      a good prognosis (seizure-free or a 50% or more reduction in seizures) and 4
      others (12%) had a poor result (frequency of seizures increased, unchanged or
      decreased less than 50%). Fifteen patients had a negative EEG response to the
      drug, 4 (27%) of whom had a favorable outcome and 11 (73%) an unfavorable result.
      These results were statistically significant. The percentage of diazepam-induced
      EEG changes in beta activity (PDICB) was also significantly positively related to
      the percentage of reduction in seizure frequency in these patients (r = 0.55, p <
      0.001). In 79% of patients with PDICB values more than 2, and 30% of those with
      values less than 2, a good outcome occurred whereas 21% and 70%, respectively,
      had a poor outcome (p < 0.001). These results showed that the patterns of EEG
      change induced by diazepam are intimately related to the outcome of epilepsy.

PMID- 8261641
TI  - Contingent negative variation in Gilles de la Tourette syndrome.
AB  - The Contingent Negative Variation (CNV) may measure arousal and attention, and is
      affected by various dopaminergic disorders. We recorded CNVs in 12 patients
      fulfilling diagnostic criteria of Gilles de la Tourette Syndrome (TS). Ten of 12
      patients were male, 10 had attention deficit disorder (ADD), and 3 also had
      obsessions and compulsions (OCD). Medication had been stopped or TS treatment not
      yet started. TS patients had higher CNV amplitude and more frequent
      postimperative negative variation than controls. CNV2 was enhanced in all TS
      patients, while CNV1 was attenuated in TS patients with ADD or OCD. This suggests
      that CNV may be increased in TS, mostly because of CNV2 and perhaps due to
      dopaminergic excess. CNV2, considered to reflect adrenergic arousal mechanisms,
      may be effected by neurobehavioral concomitants of TS. Neurophysiological
      categorization of TS patients may be possible and valuable.

PMID- 8261642
TI  - Alpha sleep: a mini review and update.

PMID- 8261643
TI  - Clinical features of anterior bradyrhythmia.
AB  - The present study examined the clinical significance of anterior bradyrhythmia
      (AB), which was described by Gibbs and Gibbs in 1964. The significance of AB in
      this report was indefinite because of unclear criteria and underdeveloped
      neuroradiology. We proposed a set of criteria of AB and reevaluated the clinical
      significance of the EEG pattern in correlation with the clinical and the
      computerized topography (CT) findings of the patients. The study material was
      4019 EEGs examined in our laboratory during a 1-year period (1991). AB was
      recorded in 20 patients (0.5%), whose mean age was 69.8 years. Its incidence
      tended to increase with age. Sixteen patients [table: see text] (80%) had
      dementia and were classified into two types according to clinical features, as
      Binswanger (B)-type and Alzheimer (A)-type. B-type patients had gait disturbance,
      urinary incontinence, hemiparesis, and ECG abnormalities, and showed leuko
      araiosis on CT. A-type patients had only dementia, and showed frontoparietal
      atrophy on CT. Delirium was found in 7 (35%) out of the 20 patients with AB,
      which may be an additional factor related to the appearance of the EEG pattern. B
      type had lower frequency of AB than A-type. Both types showed slowed background
      activities; the alpha rhythm of B-type had lower frequency and tended to have
      higher amplitude than that of A-type. These EEG abnormalities may be indicative
      of subcortical or cortical dysfunction in the frontal areas.

PMID- 8261644
TI  - Prenatal diagnosis of fragile X syndrome by direct detection of the dynamic
      mutation due to an unstable DNA sequence.
AB  - The fragile X syndrome is the most common familial form of mental retardation.
      The mutation causing the syndrome is dynamic mutation due to an unstable DNA
      (CCG)n repeat localized at Xq27.3. We have previously reported a PCR procedure to
      prepare a diagnostic probe, pPCRfx1, which can be used to determine the genotype
      of fragile X mutation individuals by Southern blot analysis. In the present
      study, pPCRfx1 was applied to the prenatal diagnosis, using chorionic villus
      cells, of a fetus which was at risk of having fragile X syndrome. In the PstI
      assay, the Southern blot showed the typical pattern of a female carrier with the
      full mutation. Analysis of the DNA methylation patterns by EcoRI + EagI assay
      showed that the EagI restriction site was not methylated on the mutated X
      chromosome of chorionic villi, but the sites were totally methylated in the brain
      and other tissues of the fetus. Thus the fetus was diagnosed to be a heterozygous
      female carrier of the dynamic mutation involved in the fragile X syndrome.

PMID- 8261645
TI  - A family with autosomal dominant polycystic kidney disease not linked to
      chromosome 16p13.3.
AB  - A family of Sicilian origin with autosomal dominant polycystic kidney disease
      (APKD) has been shown to be unlinked to chromosome 16 markers. LOD scores for the
      polymorphic markers 3'HVR and SM7 flanking the PKD 1 locus, were -1.4 and -2.33
      respectively, and theta max was 0.5 for each marker. The clinical phenotype of
      this family is consistent with that of the other non-linked families with APKD
      reported in the literature, all outside the United Kingdom, which have a milder
      progression than those linked to 16p13.3. Assuming that a clinic population
      represents the most severe forms of a disease and non PKD-1 is a less aggressive
      phenotype, the degree of genetic heterogeneity for APKD in the population may
      well be much greater than at present suggested.

PMID- 8261646
TI  - Apolipoprotein B gene DNA polymorphisms are associated with macro- and
      microangiopathy in non-insulin-dependent diabetes mellitus.
AB  - The relationship between diabetic macroangiopathy or microangiopathy and
      apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female
      patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising
      consecutive patients with poor diabetic control (HBA1 13.2% +/- 2.7 (SD))
      referred to our hospital. Plasma cholesterol and triglyceride concentrations were
      higher in the patients who were homozygous for the X2 allele (presence of XbaI
      cleavage site). Patients with the X1 allele (absence of XbaI cleavage site)
      tended to have a higher frequency of macroangiopathy, although the differences
      were not statistically significant. There was no difference in the prevalence of
      microangiopathy between the groups. In subjects with only an R1 allele (= R+;
      homozygous for the presence of EcoRI cleavage site) the prevalence of coronary
      heart disease (CHD) was observed to be high (61.9%) as compared to the subjects
      possessing an R2 allele (= R-; homozygous or heterozygous for the absence of the
      EcoRI cleavage site) (46.7%; p < 0.02). When the polymorphisms XbaI (subjects
      homozygous for the absence of the cutting site = X+; subjects homozygous or
      heterozygous for the presence of the cutting site = X-) and EcoRI were combined,
      the prevalence of macroangiopathy was observed to be high in X+R+ (80.0%) as
      compared with X+R- (44.2%), X-R+ (56.8%) and X-R- (50.0%) (p < 0.03). The
      prevalence of macroangiopathy tended to be particularly high in patients with the
      apoprotein E4 allele (phenotype E4/4 or E4/3), combined with either X+ or
      R+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261647
TI  - Mosaic trisomy 16 in a thriving infant: maternal heterodisomy for chromosome 16.
AB  - Trisomy 16 is the most common trisomy in spontaneous abortions and is usually, if
      not always, lethal in the nonmosaic state. We report a liveborn infant with
      trisomy 16 mosaicism first diagnosed by amniocentesis at 20 weeks gestation. At
      birth, the infant was growth retarded and mildly dysmorphic. At age 14 months she
      was developmentally normal and had facial asymmetry. Her length, weight and head
      circumference were normal. Pure trisomy 16 was found in cells from the placenta.
      A normal female karyotype was found in lymphocytes from the infant. Skin
      fibroblasts revealed a trisomy 16 karyotype in 6 of 30 cells. Molecular analysis
      showed maternal uniparental heterodisomy, indicating that the trisomic conceptus
      arose from a nondisjunction of maternal meiosis. Fibroblasts may be the tissue of
      choice for detection of low-level trisomy 16 mosaicism.

PMID- 8261648
TI  - Oral-facial-digital syndrome with fibular aplasia: a new variant.
AB  - The oral-facial-digital (OFD) syndromes constitute a heterogeneous group of
      entities usually associated with certain features that permit a specific
      diagnosis. This report refers to a 10-month-old girl with cleft palate, mesomelic
      limb shortening, oligopolydactyly, and fibular aplasia. Since this combination
      has not been described previously, it is proposed as a distinct type of oral
      facial-digital syndrome, and we suggest mutations of homeotic genes to explain
      some abnormalities present in the OFD syndromes.

PMID- 8261649
TI  - Alternate, adjacent 2 and 3:1 meiotic segregation products from a balanced
      t(13;18) (q12;q11) carrier.
AB  - We present a case in which alternate, adjacent 2 and 3:1 meiotic segregations
      have occurred in the pregnancies of a female carrier of a balanced reciprocal
      translocation -46,XX,t(13;18) (q12;q11). Products of five conceptions effectively
      showed trisomy 18q, trisomy 18p or monosomy 18p. This is one of the rare
      rearrangements which can give rise to a variety of segregation modes including
      adjacent 2.

PMID- 8261650
TI  - The Myhre syndrome: report of two cases.
AB  - Two unrelated patients, aged 19 and 6 years, were studied and diagnosed as having
      Myhre syndrome (MS). This review, together with three previous cases, permits
      further delineation of MS. The main features are: short stature, mental
      retardation, blepharophimosis, muscular hypertrophy, decreased joint mobility,
      thick calvarium, broad ribs, hypoplastic iliac wings and short tubular bones.
      Advanced paternal age at the propositi's birth suggests an autosomal dominant
      mutation as the cause of MS.

PMID- 8261651
TI  - Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly.
AB  - Two siblings who presented shortly after birth with signs of upper intestinal
      obstruction were successfully operated for apple peel jejunal atresia. In
      addition to intestinal malformations, both siblings exhibited severe microcephaly
      and ocular abnormalities not previously reported in this condition.

PMID- 8261652
TI  - Dacryocystitis associated with osteopoikilosis.
AB  - We report five members of a family with dacryocystitis associated with
      osteopoikilosis. The inheritance is autosomal dominant. Review of the literature
      revealed no other report of this kind of association. Osteopoikilosis must not be
      considered as a coincidental radiographic finding but as part of a systemic
      disorder.

PMID- 8261653
TI  - Consanguineous marriages among parents of patients with Down syndrome.

PMID- 8261654
TI  - Williams syndrome and subaortic stenosis.

PMID- 8261655
TI  - A1- and A2-purinoceptors in the guinea-pig uterus.
AB  - 1. Radioligand binding and functional studies were undertaken to investigate the
      P1-purinoceptors present in the separated myometrial layers and the endometrium
      of the guinea-pig uterus. 2. In preparations of endometrium-denuded circular
      myometrium, the A2-selective agonists (2-p-(2-carboxyethyl)phenethylamino-5'-N
      ethylcarboxamido-adeno sin e (CGS 21680, 100 mumol/L) and N-ethylcarboxamido
      adenosine (NECA, 1-10 mumol/L) inhibited contractile responses to phenylephrine.
      In preparations of endometrium-intact circular myometrium, NECA (10 mumol/L)
      enhanced responses to phenylephrine. NECA did not modulate the spontaneous
      contractions of longitudinal myometrium. 3. Homogenate binding studies with
      circular myometrium, longitudinal myometrium and endometrium revealed saturable
      high affinity [3H]-NECA binding sites. The mean maximal densities of binding
      sites (Bmax) were 2.08, 14.7 and 15.5 fmol/mg protein, and pKD (neg. log
      dissociation constant) values were 9.82, 9.19 and 7.44, respectively. 4. (R-) and
      (S-)-N6-(2-phenylisopropyl)adenosine (R- and S-PIA) both competed for two [3H]
      NECA binding sites in preparations of circular myometrium. CGS 21680 competed for
      two [3H]-NECA binding sites in preparations of endometrium and longitudinal
      myometrium. All other agonist competition was for one site only. The rank orders
      of potency of high affinity binding were S-PIA > or =R-PIA > or = CGS 21680
      (circular myometrium), R-PIA > CGS 21680 > or = S-PIA (longitudinal myometrium)
      and CGS 21680 > > S-PIA > or = R-PIA (endometrium). 5. In preparations of
      circular myometrium, longitudinal myometrium and endometrium the selective A1
      purinoceptor antagonist, 1,3-dipropyl-8-(2-amino-4-chloro)-phenylxanthine
      (PACPX), competed for two [3H]-NECA binding sites, the non-selective antagonist
      3,7-dimethyl-1-propargylxanthine (DMPX), competed for one site only.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8261656
TI  - Effect of breathing pattern on blood pressure and heart rate oscillations in
      humans.
AB  - 1. The relationships of respiratory sinus arrhythmia (RSA) and respiratory
      changes in systolic blood pressure (SBP) to tidal volume (VT) and breathing
      frequency (BF), were quantified during voluntary control of VT and BF in healthy
      subjects. 2. Respiration was measured non-invasively with a respiratory inductive
      plethysmograph, which was calibrated prior to each study while breathing through
      a pneumotachygraph. Finger arterial blood pressure was measured non-invasively by
      the Finapres. 3. Heart rate (HR) increased during inspiration, with a nearly
      fixed time delay for most VT and BF approximating 0.9 s. The magnitude of RSA
      increased with increases in VT and with decreases in BF. SBP decreased during
      inspiration, with a time delay which increased as BF decreased, resulting in a
      phase delay approximating 160 degrees. The magnitude of the inspiratory fall in
      SBP increased with increases in VT. Increased amplitudes of RSA and SBP variation
      occurred at the lowest BF, consistent with the possibility of interactions
      between respiratory-related influences and those due to 'slow waves' of vasomotor
      tone. 4. The present results are consistent with the conclusion that respiratory
      effects on SBP are caused by a mechanism other that simply changes in HR.

PMID- 8261657
TI  - 11 beta-Hydroxysteroid dehydrogenase activity in mesenteric arteries of
      spontaneously hypertensive rats.
AB  - 1. 11 beta-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries
      of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was
      determined and expressed as the percentage conversion of [3H]-corticosterone to
      [3H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in
      mesenteric arteries of both 4 and 9 week old SHR (8.4 +/- 0.8%, 5.0 +/- 1.5%,
      respectively) compared with WKY rats (12.4 +/- 0.6%, 15.8 +/- 0.7%, respectively;
      P < 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and
      endothelial cells (EC) were prepared with selective precipitation in 3 mol/L
      LiCl/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC
      but its mRNA expression was not detected in EC, using northern blot analysis. 4.
      The results in this study indicate that 11-HSD in the vascular wall may play a
      role in the pathogenesis of hypertension in SHR.

PMID- 8261658
TI  - Effects of hydroxocobalamin and haemoglobin on no-mediated relaxations in the rat
      anococcygeus muscle.
AB  - 1. The effects of hydroxocobalamin (Vitamin B12a) on relaxations produced by
      nitric oxide (NO), some NO-donating compounds and nitrergic nerve stimulation in
      isolated preparations of the rat anococcygeus muscle were compared with the
      effects of haemoglobin. 2. Hydroxocobalamin (30 mumol/L) significantly reduced
      relaxations induced by NO (0.1-3 mumol/L) and sodium nitroprusside (SNP; 0.01-0.3
      mumol/L) but did not affect relaxations induced by glyceryl trinitrate (GTN; 0.01
      1 mumol/L), S-nitrosocysteine (0.1-0.3 mumol/L) or stimulation of nitrergic
      nerves. A higher concentration of hydroxocobalamin (100 mumol/L) slightly reduced
      nitrergic nerve stimulation-induced relaxations. 3. Haemoglobin (10 mumol/L)
      blocked relaxation induced by NO and reduced relaxations induced by SNP, GTN, S
      nitrosocysteine and nitrergic nerve stimulation. 4. When nitrergic nerve
      stimulation-induced relaxations had been partially reduced by the NO synthase
      inhibitor L-NAME (5-10 mumol/L), hydroxocobalamin had only a weak and transient
      inhibitory effect. 5. Noradrenergic contractions induced by field stimulation
      were not affected by hydroxocobalamin (30 mumol/L), but were enhanced by
      haemoglobin (10 mumol/L). 6. The results suggest that the transmitter released
      from nitrergic nerves in anococcygeus muscles resembles NO-releasing compounds
      such as S-nitrosocysteine and GTN but not SNP or free NO.

PMID- 8261659
TI  - Effects of verapamil and diltiazem on dopamine release in the central nervous
      system of spontaneously hypertensive rats.
AB  - 1. The purpose of the present study was to investigate the effects of Ca(2+)
      antagonists (verapamil and diltiazem) on dopamine release in the central nervous
      system in hypertension. 2. Striatal slices obtained from spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were prelabelled with [3H]
      dopamine, and superfused with Krebs-Ringer solution in vitro. The slices were
      stimulated electrically at a frequency of 1 Hz. 3. Stimulation-evoked release of
      [3H]-dopamine from striatal slices was significantly decreased in SHR compared
      with WKY rats. 4. Exposure of slices to verapamil and diltiazem significantly
      increased the stimulation-evoked [3H]-dopamine release. The facilitatory effects
      of the Ca(2+)-antagonists on dopamine release were significantly greater in SHR
      than in WKY rats. 5. Because central nervous system dopaminergic mechanisms
      appear to be depressor, the results suggest that the pronounced effects of
      verapamil and diltiazem on dopamine release in SHR might be involved in the
      central hypotensive mechanisms of the Ca(2+)-antagonists.

PMID- 8261660
TI  - Influence of somatostatin analogue (SMS 201-995, octreotide) on blood pressure in
      adrenocorticotrophin (ACTH) treated rats: role of hyperinsulinaemia in ACTH
      hypertension.
AB  - 1. The hypothesis that adrenocorticotrophin (ACTH)-induced hypertension is a
      consequence of steroid-induced hyperinsulinaemia was tested using the
      somatostatin analogue (sandostatin, octreotide) to inhibit insulin release in
      Sprague-Dawley (SD) rats (n = 41). 2. Octreotide (20 micrograms, twice daily) did
      not modify blood pressure, plasma glucose, bodyweight, water and electrolyte
      balance, or organ weights but inhibited insulin secretion in the SD rat. 3.
      Compared with sham injection, ACTH-treated (0.5 mg/kg per day) SD rats showed an
      increase in blood pressure (sham 111 +/- 4 mmHg; ACTH 140 +/- 5 mmHg on treatment
      day 10 (P < 0.01), organ weights, water intake, urine volume, plasma glucose,
      insulin and sodium concentrations, and decrease of bodyweight and plasma
      potassium concentration. 4. Systolic blood pressure in rats treated with combined
      octreotide and ACTH was similar to that in rats on ACTH alone. Plasma insulin
      concentration was lower in octreotide + ACTH treated rats than with ACTH
      treatment alone. There were no differences in body or organ weights, plasma
      glucose, water or electrolyte balance. 5. Octreotide lowered plasma insulin
      concentration to the normal range but did not modify ACTH-induced hypertension in
      SD rats. These data do not support the notion that insulin-mediated alterations
      in blood pressure are a major mechanism for ACTH-induced hypertension in the rat.

PMID- 8261661
TI  - Effects of naftidrofuryl on isolated perfused kidneys of spontaneously
      hypertensive rats.
AB  - 1. Experiments were designed to determine the effects of low concentrations (5
      500 nmol/L) of naftidrofuryl, a 5-hydroxytryptamine (5-HT) antagonist, on renal
      functions and prostanoid synthesis responses to noradrenaline (NA) and 5-HT.
      Isolated kidneys of 8 week old male spontaneously hypertensive rats were perfused
      at a constant flow rate in a single-pass system. 2. In baseline conditions,
      naftidrofuryl did not modify the renal vascular resistance and the glomerular
      filtration rate (GFR), although it elicited a significant but not dose-dependent
      increase in the venous excretion of 6-keto-prostaglandin (PG) F1 alpha and
      thromboxane (Tx)B2, the stable end-products of PGI2 and TxA2, respectively. 3. NA
      increased renal vascular resistance and GFR in a dose-dependent manner and
      enhanced the venous excretion of 6-keto-PGF1 alpha and TxB2. Naftidrofuryl
      significantly attenuated the effects of NA on renal vascular resistance,
      abolished those on GFR and enhanced, at the highest concentration (500 nmol/L)
      only, those on 6-keto-PGF1 alpha excretion. 4. 5-HT increased renal vascular
      resistance but not GFR. It did not change the sodium excretion and the release of
      6-keto-PGF1 alpha and TxB2. Naftidrofuryl blunted the RVR response to 5-HT
      without change in the prostanoid release. The inhibitory action of naftidrofuryl
      was not modified by indomethacin which, by itself, prevented the vasoconstrictor
      response to 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261662
TI  - Effects of high salt intake on control of hindlimb vascular resistance by
      arterial baroreflex and vagal afferents in spontaneously hypertensive rats.
AB  - 1. This study aimed to examine whether a high salt diet alters control of
      vascular resistance by arterial baroreflex and vagal afferents in spontaneously
      hypertensive rats (SHR) and Wistar Kyoto rats (WKY). 2. SHR and WKY aged 8 weeks
      were fed either high (8%) or normal salt (0.4%) diet for 4 weeks. Arterial
      baroreflex control of hindlimb vascular resistance was assessed by examining
      reflex-induced vasodilation and vasoconstriction in response to phenylephrine and
      nitroprusside, respectively, in the constant-flow perfused hindlimb of urethane
      anesthetized rats. 3. Tonic influence of the cardiopulmonary vagal afferents was
      evaluated by examining the effects of vagotomy on hindlimb vascular resistance
      and on the gain of arterial baroreflex control of hindlimb vascular resistance.
      4. The gain of the arterial baroreflex control of hindlimb vascular resistance in
      response to both phenylephrine and nitroprusside were not significantly different
      between SHR receiving high and normal salt diets, and between WKY receiving high
      and normal salt diets. 5. Vagotomy increased hindlimb vascular resistance in all
      four groups of rats. However the high salt diet than those in SHR on a normal
      salt diet but similar between the two groups of WKY. Vagotomy increased the slope
      of arterial baroreflex control of hindlimb vascular resistance in SHR receiving a
      normal salt diet and the two groups of WKY but not in SHR receiving a high salt
      diet.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261663
TI  - Prevention of joint destruction in antigen-induced arthritis.
AB  - In rheumatoid arthritis (RA) erosive joint changes are the dominating cause of
      chronic disability. In a cohort of patients with RA followed from early stages of
      the disease, we have observed a much larger prevalence of destructions in hips
      than in knee joints. The latter were frequently injected with triamcinolone
      hexacetonide in contrast to the former. In order to elucidate a possible role of
      local glucocorticoids we studied the antigen-induced arthritis model of Dumonde
      and Glynn in rabbits which, untreated, caused advanced joint destruction in 3/5
      animals, whereas 0/14 animals receiving 3 injections of triamcinolone
      hexacetonide developed no such changes. The treatment was effective when started
      up to 2 weeks after induction of the arthritis. It is suggested that locally
      administered glucocorticoids may prevent or delay large joint destruction in RA.

PMID- 8261664
TI  - Interaction between circulating amyloid fibril protein precursors and
      extracellular tissue matrix components in the pathogenesis of systemic
      amyloidosis.
AB  - Amyloidosis is a heterogeneous group of diseases characterized by deposition of a
      fibrillar, proteinaceous material, amyloid, in various tissues and organs.
      Increasing knowledge about the different proteins that constitute the amyloid
      fibrils has made it possible to classify amyloidosis by the fibril protein, which
      appears more rational than the traditional classification by its clinical
      expression. A serum protein is the precursor of the amyloid fibril protein in the
      various systemic forms of amyloidosis. Although the chemical composition of
      amyloid is presently well known, the pathogenetic processes that convert such
      proteins into a fibrillar form and lay them down in the tissues are far from
      clarified. We suggest some pathogenetic mechanisms for amyloid deposition,
      involving different types of fibril protein, their precursors, the extra
      fibrillar amyloid P component, glycosaminoglycans, proteoglycans, and calcium
      with special reference to experimental work from our research group.

PMID- 8261665
TI  - Decreased autoantibody levels and enhanced survival of (NZB x NZW) F1 mice
      treated with C-reactive protein.
AB  - C-Reactive protein (CRP) is the prototypic acute-phase serum protein in man. On
      the basis of its binding specificities and activities, it has been proposed that
      CRP facilities the removal of nuclear material released from damaged cells. To
      determine whether such a process could alter the development of autoimmunity to
      nuclear antigens, the effect of CRP on autoimmune disease in the (NZB x NZW) F1
      mouse model of systemic lupus erythematosus was tested. Mice were injected with
      chromatin bound to latex beads in the presence or absence of bound CRP. CRP
      treatment significantly prolonged survival of mice injected with chromatin-coated
      beads. CRP also produced a transient decrease in IgG antibody levels to histones,
      DNA, and DNP, suggesting a general suppressive effect on ongoing antibody
      responses. To determine whether CRP would affect chromatin clearance, the effect
      of CRP on nucleosome core particle clearance was tested in BALB/c mice. CRP
      pretreatment did not alter the rate of clearance or organ localization of
      nucleosome core particles. These findings indicate that CRP can modify the course
      of autoimmune disease possibly by preventing the exposure of nuclear antigens to
      the immune system.

PMID- 8261666
TI  - Streptococcal adherence to Langerhans cells: a possible step in the pathogenesis
      of streptococcal pharyngitis.
AB  - Group A streptococci are nonmotile and have no structures that would enable them
      to penetrate submucosally into the pharynx. We have postulated that they adhere
      to host pharyngeal mucosal cells called Langerhans cells that are motile and
      could transport them into deeper tissues. We used a microscopic assay to assess
      the adherence of streptococci to cells from normal pharyngeal scrapings after the
      cells and bacteria were incubated in vitro. Langerhans cells were identified by
      immunofluorescent staining for the CD1a antigen. Nonstaining cells were
      considered to be keratinocytes. Of the 2279 cells examined from 9 subjects, 92.6%
      were keratinocytes and 7.4% were Langerhans cells. Only 1.8% of the 2111
      keratinocytes had > 50 bacteria attached in this assay, while 76.2% of the 168
      Langerhans cells had > 50 attached bacteria. Thus, under the conditions of this
      study, group A streptococci adhere preferentially to Langerhans cells from the
      pharynx. Adherence to these motile cells may provide a mechanism through which
      pathogenic streptococci may be transported into submucosal tissues.

PMID- 8261667
TI  - IgG subclass distribution and complement activation ability of autoantibodies to
      neutrophil cytoplasmic antigens (ANCA).
AB  - To study the IgG subclass distribution and complement activation ability of ANCA,
      24 sera containing C-ANCA (cytoplasmatic) and 7 sera containing P-ANCA
      (perinuclear), as determined by a routine immunofluorescence test, were examined.
      The subclass distribution was tested by the use of immunofluorescence and ELISA
      technique and monoclonal antibodies to IgG subclasses. The complement activating
      activity was studied by the use of immunofluorescence technique and antibodies to
      C3c and the terminal complement complex (TCC, C5b-9), directed against a
      neoepitope on C9. For C-ANCA, IgG1 and IgG4 were the dominating subclasses. The
      subclass distribution differed from that of other autoantibodies tested and that
      of the total IgG subclass concentrations. For P-ANCA, the results were
      inconclusive, but the lack of IgG3 was striking. All of the C-ANCA-containing
      sera caused deposition of C3c, and 50% of the sera gave formation of TCC when
      reacting with ethanol-fixed granulocytes. P-ANCA-containing sera caused some C3c
      deposition, but not TCC formation. The unusual IgG subclass distribution for C
      ANCA is possibly due to repeated antigenic stimulations and/or to T cell factors
      influencing the antibody isotype switching. Despite the high IgG4 activity, sera
      containing C-ANCA are often able to activate complement and are therefore
      potentially harmful.

PMID- 8261668
TI  - Distribution of glycosylation abnormality among serum IgG subclasses from
      patients with rheumatoid arthritis.
AB  - IgG from patients with rheumatoid arthritis possess significantly fewer galactose
      residues in its sugar chains. We made an attempt to analyze the distribution of a
      galactosylation defect among IgG subclasses by immunoassay using PVL, a recently
      described lectin specific for N-acetylglucosamine (GlcNAc). A distinct difference
      between RA and normal controls was present in IgG2 (P = 0.0007). A less
      remarkable but significant difference was seen in IgG1 (P = 0.0118) and in IgG4
      (P = 0.022). A significant difference was not observed in IgG3 (P = 0.169). The
      possible relationship between such a glycosylation abnormality and RF production
      was discussed.

PMID- 8261669
TI  - The phylogeny of proteinase 3/myeloblastin, the autoantigen in Wegener's
      granulomatosis, and myeloperoxidase as shown by immunohistochemical studies on
      human leukemic cell lines.
AB  - Proteinase 3/myeloblastin (Pr3/MBN) is a serine protease found in primary
      granules of neutrophilic granulocytes and monocytes in man. This enzyme has been
      identified as the main autoantigen in Wegener's granulomatosis. Pr3/MBN was
      earlier identified in the promyelocytic cell line HL-60 and was assumed to be at
      least partly responsible for controlling proliferation and differentiation within
      the granulocytic-monocytic system. We have investigated 98 leukemic cell lines
      representing all lineages of the hemopoietic system. Pr3/MBN was found to appear
      in mature myeloblastic precursors and in CD34+ immature monoblastic cells and was
      restricted to the granulocytic and monocytic lineage. Myeloperoxidase (MPO) was
      found to be expressed earlier in development in the granulocytic lineage, but
      appeared later than Pr3/MBN in the monocytic lineage. The identification of cell
      lines which contained Pr3 only or MPO only may make them useful for demonstration
      of anti-neutrophil cytoplasmic antibodies in primary vasculitides.

PMID- 8261670
TI  - IgG2 deficiency in primary Sjogren's syndrome and hypergammaglobulinemic purpura.
AB  - Total IgG and IgG subclasses were studied in 34 patients with primary Sjogren's
      syndrome and 4 with hypergammaglobulinemic purpura. Total IgG was elevated in
      30/34 patients with Sjogren's syndrome. IgG1 increase was responsible for the
      main part of total IgG increase, contrasting with low levels of IgG2. The
      difference in IgG1/IgG2 ratio between 38 patients as a group and 40 normal
      controls was statistically highly significant, but was not seen in all patients.
      Six patients had markedly low levels of IgG2, but only two had severe repeated
      respiratory infections. These observations probably reflect selective
      autoantibody restriction to the IgG1 subclass. We conclude that patients with
      Sjogren's syndrome may be IgG2 subclass deficient despite elevated levels of
      total IgG, but also that such deficiency in most instances does not cause a
      tendency to infections. IgG subclass analysis may be of value to characterize
      polyclonal IgG increase, since IgG1 subclass predominance often indicates
      autoimmune disease.

PMID- 8261671
TI  - T lymphocytes from patients with systemic lupus erythematosus show increased
      response to interleukin-2 after costimulation with OKT3 monoclonal antibody and
      phorbol esters.
AB  - In the present study we have examined the potential contribution of IL-2/IL-2R
      interactions in CD3-mediated responses by T lymphocytes from patients with
      systemic lupus erythematosus (SLE). T-cells from SLE patients showed normal IL-2
      production when activated with OKT3 MAb and submitogenic concentrations of PMA,
      in cultures in which uptake of endogenous IL-2 was prevented by pretreatment with
      anti-Tac MAb. In contrast, PHA-induced IL-2 production was lower in patients
      under the same conditions. Under these stimulatory conditions the proportions of
      T-cells expressing IL-2R CD25 molecules was comparable in patients and controls.
      There was earlier and higher binding of exogenously added IL-2 in T lymphocytes
      from patients activated via the CD3 pathway. Furthermore, these cells responded
      to IL-2 with stronger proliferative responses than cells from control subjects.
      These findings may partly explain the increased proliferative responses of SLE T
      cells when stimulated via the CD3 pathway.

PMID- 8261672
TI  - Selective, prolonged alteration of complement-mediated immune clearance after
      acute exposure of mice to ethanol.
AB  - A selective and prolonged alteration in complement-mediated immune clearance was
      found in mice given a single intraperitoneal injection of ethanol. Rate constants
      for the separate components of complement- and IgG Fc gamma-mediated clearance
      were determined using a branched series, first-order reaction sequence model and
      measurements of the disappearance of radiolabeled IgG-opsonized murine
      erythrocytes from the circulation of BALB/c mice. The rate constant governing
      immune clearance mediated by IgG Fc gamma receptors (k3) decreased to 16% of
      control at 1 hr after ethanol injection but returned to normal in 72 hr. A > 50%
      decrease in complement-mediated clearance occurred, with a nadir of complement
      mediated sequestration (k1) and complement-dependent phagocytosis (k4) at 1 hr (P
      < 0.001). In this case, however, k1 and k4 rate constant values did not return to
      control levels until 6 weeks after the injection of ethanol. The rate constant
      governing C3b deactivation and release of deactivated, sensitized cells back to
      the circulation before they undergo phagocytosis (k2) was initially normal, but
      decreased in Week 6 and remained low to the end of the observation period at 22
      weeks (P < 0.0001). These changes resulted in a major reduction in overall
      complement-mediated immune clearance up to 4 weeks after the ethanol injection.
      The change to normal rates for sequestration and phagocytosis coupled with
      decreased deactivation and release at 6 weeks postinjection resulted in a small
      increase in overall complement-mediated clearance that persisted through Week 22.

PMID- 8261673
TI  - The impact of the ADA on colleges of nursing.

PMID- 8261674
TI  - Continuous renal replacement therapies for the treatment of acute renal failure
      in intensive care patients.
AB  - Continuous renal replacement therapies are extensively utilized for the treatment
      of acute renal failure in the critically ill patient. The arterio-venous
      circulation has been partially substituted by the veno-venous pump driven
      circulation. Diffusion has been added to convection in order to increase the
      small solutes clearance even though sometimes the pure convection is still
      advantageously utilized. Hemofilters have been changed in hemodiafilters with the
      possibility of countercurrent dialysate circulation. The blood path geometry has
      been specifically designed to operate under conditions of low pressure and flow.
      Therefore lower amounts of heparin are required to maintain the extracorporeal
      anticoagulation with a reduced risk of bleeding. New techniques and new materials
      permit us today to carry out continuous therapies with a low rate of
      complications and an increased percentage of survival among the treated patients.
      The improved understanding of the multiple organ failure syndrome and the
      pathophysiology of the septic syndrome, suggest today newer indications for
      continuous renal replacement therapies. The proposed mechanisms of action of the
      therapy should be the removal of chemical mediators such as platelet activating
      factor, interleukin-1 and tumor necrosing factor alfa, not only by a filtration
      process, but also by the adsorption on the surface and structure of the
      artificial membrane. These new mechanisms may in part be responsible for the
      beneficial effects of continuous therapies in the patients affected by acute
      renal failure and other organ dysfunctions.

PMID- 8261675
TI  - Glomerular anionic sites in minimal change nephrotic syndrome and focal segmental
      glomerulosclerosis.
AB  - In order to examine the changes in charge of the glomerular basement membrane
      (GBM) in nephrotic syndrome, anionic sites in the GBM were studied
      quantitatively. Renal biopsy specimens were obtained from 5 children with minimal
      change nephrotic syndrome (MCNS) and 5 with nephrotic syndrome and focal
      segmental glomerulosclerosis (FSGS). Biopsy specimens obtained from 5 patients
      without proteinuria were also examined as controls. Anionic sites were stained
      with polyethyleneimine (PEI) as a cationic probe and were examined by electron
      microscopy. The number of PEI-labeled anionic sites in the lamina rara externa of
      the GBM was counted in the glomerular capillary region and in the paramesangial
      region separately. The number of anionic sites per 1000-nm GBM was 20.9 +/- 0.6
      in the capillary and 21.2 +/- 0.7 in the paramesangium in controls. They were
      significantly decreased in MCNS (16.5 +/- 0.7 in the capillary and 16.9 +/- 0.5
      in the paramesangium, p < 0.001) and in FSGS (16.7 +/- 0.7 in the capillary and
      17.0 +/- 0.6 in the paramesangium, p < 0.001). The decrease of anionic sites
      suggests a defect in the charge-selective barrier in the lamina rara externa of
      the GBM in MCNS and FSGS, and this defect both in the capillary and in the
      paramesangium may be responsible for the proteinuria in these two conditions.

PMID- 8261676
TI  - Diagnosis and treatment of a solitary infected hepatic cyst in two patients with
      adult polycystic kidney disease.
AB  - We report on two women (one 52-year-old who underwent kidney transplantation 15
      months ago and the other, 71-year-old, undergoing hemodialysis) both with adult
      polycystic kidney disease who had to be hospitalized because of recurrent fever
      attacks up to 40 degrees C without any remarkable abdominal symptoms.
      Staphylococcus hominis and E. coli were recovered respectively from blood
      cultures of both patients. Evidence for the presence of a solitary infected cyst
      in the liver could only be obtained by computed tomography (CT) with i.v.
      administration of a contrast medium. In both cases the infected liver cyst was
      non-operatively drained with a CT-guided percutaneous catheter and therefore the
      necessity of laparotomy was avoided.

PMID- 8261677
TI  - Evaluation of protein intake by dietary diaries and urea-N excretion in children
      with chronic renal failure. European Study Group for Nutritional Treatment of
      Chronic Renal Failure in Childhood.
AB  - In 1988 a European multicentre, randomized trial was started in order to analyse
      the influence of protein intake on the progression of chronic renal failure in
      children. Compliance to the dietary prescriptions, i.e. protein intake, was
      checked by written dietary diaries and in addition by urinary urea-N excretion.
      This provided a unique chance to compare both methods in non-hospitalized
      children. Of a total of 200 patients 123 were selected, in whom at least 4
      consecutive dietary diaries plus 4 completely collected 24-hour urine samples
      were available. Whereas urea-N excretion and simultaneously recorded protein
      intake did not correlate well, mean urinary urea-N excretion and mean protein
      intake of at least 4 observations in each patient correlated highly (r = 0.803, p
      = 0.0001). The difference between protein-N intake and urea-N excretion was not a
      constant amount of 0.031 g/kg/day as proposed by Maroni et al. [1985] but figured
      at 0.085 +/- 0.061 g/kg/day and was highly correlated to protein intake (r =
      0.839, p = 0.0001). The correlation of protein intake and urea-N excretion was
      best described by the formula: protein-intake (g/kg/day) = (urea-N excretion
      [g/kg/day]x 15.39) -0.8 or protein intake (g/kg/day) = urea-N excretion
      (g/kg/day) x 9.5. Maroni's formula underestimated the high protein intake of
      young children. In only a few patients dietary diaries severely underestimated
      protein intake as compared to calculation by urea-N excretion.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8261678
TI  - Comparison of intermittent oral and intravenous calcitriol in hemodialysis
      patients with secondary hyperparathyroidism.
AB  - Both intermittent intravenous and intermittent oral calcitriol have been shown to
      be effective in the treatment of secondary hyperparathyroidism in hemodialysis
      patients and it has been claimed that intravenous calcitriol causes less
      hypercalcemia. However, there has been no published systematic comparison of the
      two routes of administration of intermittent calcitriol. Therefore in a
      prospective crossover study 11 (9 male) patients on maintenance hemodialysis were
      randomized to receive intravenous followed by oral calcitriol for 4 months each,
      or oral followed by intravenous calcitriol, commencing at 2 micrograms
      postdialysis three times per week. Initial serum immunoreactive parathyroid
      hormone (PTH) was 446 +/- 111 (normal < 65) pg/ml. Calcium-containing phosphate
      binders were not used. Calcitriol was ceased if hypercalcemia developed and
      restarted at 2 micrograms or 1 microgram when calcium returned to normal.
      Hypercalcemia was frequent (11 episodes in 8 patients on intravenous calcitriol
      and 10 episodes in 7 patients on oral calcitriol) and dose reduction to 1
      microgram was necessary in 7 patients on intravenous and on 6 patients on oral.
      Serum PTH fell during both treatments. Parathyroid enlargement was seen in 10
      glands from 4 patients, but no size reduction was demonstrated with treatment.
      There was no reduction in activity on quantitative metabolic bone scan. In
      summary, intermittent oral calcitriol and intermittent intravenous calcitriol
      were equally effective in reducing serum parathyroid hormone levels and at a dose
      of 2 micrograms postdialysis caused hypercalcemia with equal frequency.

PMID- 8261679
TI  - Long-term studies using a calcium-free dialysate.
AB  - In this prospective controlled study the purpose was to assess the long-term
      safety of calcium-free dialysate (O Ca) for hemodialysis and to determine the
      optimum calcium replacement. With this technique there is no calcium in the
      dialysate and calcium is infused into the drip chamber distal to the dialyzer. We
      compared the use of a standard bicarbonate dialysate with a calcium free
      dialysate in two groups of patients. One group (study 1) received 10 mmol/hour Ca
      replacement, the other (study 2) received 13.3 mmol/hour Ca during dialysis. Each
      O Ca period lasted six months. This experimental period was compared with the six
      months preceding and following in the same patient and as well, with a concurrent
      control group who received standard bicarbonate dialysis either with 1.5 mmol/l
      calcium in the dialysate in study 1 or 1.75 mmol/l in study 2. Each group had
      nine to eleven subjects. No adverse effects were seen in either of the studies.
      With 10 mmol/hour calcium replacement there was a small but not significant rise
      in the pre-dialysis intact parathyroid hormone level (PTH) whereas in all the
      other groups it remained the same or fell. There was significantly less rise in
      the post-dialysis calcium in the same group and this was associated with a small
      but not significant fall in both pre-dialysis total and ionized calcium. It was
      concluded that the O Ca technique can be used for long periods and that 13.3
      mmol/hour is a satisfactory replacement using Discap 140 dialyzers or their
      equivalent.

PMID- 8261680
TI  - Serum ionized calcium, parathyroid hormone and phosphate in uremic patients
      during and between hemodialysis.
AB  - The serum concentrations of actual ionized calcium (at actual pH), adjusted
      ionized calcium (at pH 7.4), pH, intact parathyroid hormone (PTH) and phosphate
      were studied in ten patients during and between two hemodialysis sessions using a
      dialysate containing 1.66 mmol/l of calcium. Actual ionized calcium and adjusted
      ionized calcium increased during hemodialysis from 1.19 to 1.38 and 1.43 mmol/l,
      respectively (mean values) and returned to predialysis values within five and
      nine hours postdialysis. Serum PTH decreased from 165 ng/l to 55 ng/l (median
      values) during hemodialysis but two-hour postdialysis the level did not differ
      significantly from the predialysis level. Serum phosphate decreased from 2.05
      mmol/l to 1.11 mmol/l during hemodialysis, and increased slowly towards the
      predialysis level. The level of pH increased from 7.40 to 7.47 during
      hemodialysis and reached predialysis level after nine hours. In a multivariate
      analysis including actual and adjusted ionized calcium, pH, phosphate and PTH,
      only actual or adjusted ionized calcium was associated with the level of PTH. We
      conclude that the effect of dialysate calcium on the levels of ionized calcium
      and PTH is of very short duration postdialysis.

PMID- 8261681
TI  - Plasma homocysteine in renal failure.
AB  - Plasma homocysteine in three different groups of patients with chronic renal
      failure (one group without dialysis, one with CAPD and one with hemodialysis) was
      increased compared to controls. Another group of patients with slightly reduced
      renal dysfunction (normal serum creatinine but reduced glomerular filtration
      rate) did not, however, show increase of plasma homocysteine. The clearance of
      homocysteine as a percentage of creatinine clearance in the three different
      groups of patients with chronic renal failure was also significantly increased
      compared to controls. Thus the clearance of homocysteine was not affected to the
      same extent as that of creatinine in renal failure. This may be attributed to the
      fact that, besides the reduced glomerular filtration rate, a depressed tubular
      uptake of homocysteine may occur in chronic renal failure. We were also able to
      show that neither in patients with varying renal function nor in controls were
      there any significant diurnal variation of plasma homocysteine, despite the
      intake of a protein-rich meal. However, after methionine loading in eight
      patients with severe chronic renal failure, a slight but significant increase of
      plasma homocysteine was noted. This indicates a disturbed metabolism with high
      amounts of homocysteine, which might be mainly attributed to an impaired
      transulphuration pathway.

PMID- 8261682
TI  - The effect of high-dose pyridoxine and folic acid supplementation on serum lipid
      and plasma homocysteine concentrations in dialysis patients.
AB  - Pyridoxine and folic acid supplementation in dialysis patients is a matter of
      debate. This study was performed to estimate the effects of pharmacologic doses
      of these vitamins on serum lipid and plasma homocysteine concentrations, which
      are known to be high in dialysis patients. Both hemodialysis and continuous
      ambulatory peritoneal dialysis patients were included in the study. Pyridoxine
      supplementation had a mild but significant cholesterol-lowering effect (7%).
      Folic acid supplementation significantly lowered plasma homocysteine
      concentrations by a mean of 30%. There was a strong, inverse correlation between
      blood folate and plasma homocysteine concentrations. These results indicate that
      daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial
      effect on the cardiovascular risk profile in dialysis patients.

PMID- 8261683
TI  - Therapeutic efficiency of phlebotomy in posttransplant hypertension associated
      with erythrocytosis.
AB  - Hypertension is a major complication in kidney transplantation and contributes to
      the high cardiovascular mortality of renal transplanted recipients. The aim of
      the present study was to evaluate the therapeutic effect of phlebotomy on blood
      pressure in posttransplant hypertension associated with erythrocytosis. In 12
      renal transplanted patients (7 male, 5 female, aged 29-52 years) with
      erythrocytosis (defined by hematocrit > 52% or hemoglobin > 170 g/l), a 24-hour
      monitoring of blood-pressure and heart rate (SpaceLabs SL90207) was performed
      before, 2 and 6 weeks after phlebotomy. Patients with iron-deficiency and/or
      transplant rejection were excluded from the study. Ten of 12 patients were on
      antihypertensive treatment before phlebotomy. Phlebotomy (500 ml) was repeated
      three times on average within the first two weeks, until hematocrit decreased
      below 45%. The phlebotomy therapy lowered the hematocrit after two weeks from
      54.8 +/- 2.8% to 44.3 +/- 4.2% and 43.0 +/- 5.6% after six weeks. Before
      phlebotomy, the blood pressure was systolic 153.2 +/- 15.1 mmHg and diastolic
      95.2 +/- 9.5 mmHg. After repeated phlebotomy, there was a significant decrease of
      blood pressure to systolic 139.0 +/- 14.1 and diastolic 85.3 +/- 8.2 mmHg (p <
      0.01). Without change of hematocrit and hemoglobin, there was no further change
      of blood pressure after six weeks (systolic 140.1 +/- 9.9 mmHg, diastolic 86.3 +/
      9.5 mmHg). The heart rate did not change significantly during the therapy. The
      antihypertensive treatment could be reduced in most of the patients. The present
      study demonstrates the therapeutic effect of phlebotomy in posttransplant
      hypertension associated with erythrocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261684
TI  - Gastrointestinal absorption of aluminum in rats using 26Al and accelerator mass
      spectrometry.
AB  - Using the technique of Accelerator Mass Spectrometry (AMS), 26Al has been
      measured in plasma, liver, urine and bone of normal rats at 8, 24 and 48 hours
      after ingestion of trace amounts of Al (3.8 ng of 26Al and 63 ng of stable 27Al),
      both in citrate-free and citrate-containing solutions. Our data show that under
      physiological conditions, namely at normal levels of dietary intake, intestinal
      Al absorption is approximately 0.04%, and is not significantly enhanced by the
      presence of citrate. Interestingly, the amount of Al retained by bone (0.02%) is
      comparable to that excreted in urine during 48 h (0.02%). Our estimate of
      gastrointestinal absorption is more than two orders of magnitude smaller than
      that estimated by Day et al. [1991], also using 26Al, for a single human subject.

PMID- 8261686
TI  - Non-invasive prenatal fetal testing by analysis of maternal blood.
AB  - As the number of women undergoing invasive prenatal diagnosis for cytogenetic,
      molecular, or biochemical testing is increasing, the development of new non
      invasive methods of analyzing fetal cells is imperative. We have analyzed blood
      from 27 pregnant women (gestational age of 10-11 weeks) by the polymerase chain
      reaction (PCR) with oligonucleotide primers specific for Y sequences. The
      sensitivity of our assay, which did not include a step for fetal cell selection
      prior to PCR analysis, was 45% and the specificity was 89%. A review of the
      published studies of non-invasive prenatal diagnosis is provided. We conclude
      from our results and those of others that it is feasible to amplify fetal
      specific sequences from maternal blood. However, techniques such as fluorescence
      activated or magnetic-activated cell sorting of the maternal blood, as used in
      other studies, are necessary to enrich for fetal cells prior to analysis. With
      further improvements of these techniques, it is likely that fetal cell typing
      from maternal blood will be a feasible method of non-invasive prenatal diagnosis.

PMID- 8261685
TI  - Age-related changes of urinary pyridinoline and deoxypyridinoline in Japanese
      subjects.
AB  - Urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) are commonly used as
      bone resorption markers because they are more sensitive to bone resorption than
      is urinary hydroxyproline. Age-related changes of urinary Pyr and D-Pyr were
      studied in 337 healthy females, aged 1 to 93 y, and 113 healthy males, aged 3 to
      75 y. Levels of urinary Pyr and D-Pyr follow a characteristic pattern as one
      ages, with very high values during childhood decreasing to low baseline levels in
      adulthood between 20 and 49 y. Both values in the 0-19 y age group were
      significantly higher than those in the other age groups for both sexes. These
      values increased moderately but significantly in females in the 50-59 y age group
      compared to those in the 40-49 y age group (Pyr: 26.4 +/- 7.6 vs. 19.3 +/- 6.2
      nmol/mmol creatinine, p < 0.05; D-Pyr: 7.7 +/- 2.4 vs. 5.6 +/- 2.2 nmol/mmol
      creatinine, p < 0.05). In contrast, these values stayed at low levels in the 50
      59 y age group in males. The values of urinary Pyr and D-Pyr were significantly
      higher in females than in males in the 50-59 y age group (females vs. males--Pyr:
      26.4 +/- 7.6 vs. 17.0 +/- 3.9 nmol/mmol creatinine, p < 0.05; D-Pyr: 7.7 +/- 2.4
      vs. 4.7 +/- 1.2 nmol/mmol creatinine, p < 0.05). In our cross-sectional study,
      the values of urinary Pyr and D-Pyr increased in childhood (0-19 y), and in the
      early postmenopausal period (50-59 y). These 2 urinary markers reflect the age
      related changes of bone resorption.

PMID- 8261687
TI  - Inhibition of HIV-1 replication by daunorubicin.
AB  - Members of the anthracycline family of drugs such as daunorubicin (DNR) are
      currently being employed in cancer therapy, treatment of Kaposi's sarcoma and
      lymphomas in HIV-1 infected patients. These drugs may have an anti-viral activity
      against HIV-1. Experiments conducted on U937 (a promonocytic cell line),
      peripheral blood monocytes (without T cells) and infected with HIV-1 showed anti
      viral activity at nanogram/ml concentrations, without affecting cell
      proliferation and cell viability. Treatment of Hut 78 cells (a T cell line) with
      DNR was not as effective in inhibiting HIV-1 replication when compared to the
      anti-HIV activity in cells of the monocyte lineage.

PMID- 8261688
TI  - Relationship of the antihypertensive effect of vasopressin withdrawal to sodium
      excretion in the Doca-salt hypertensive rat.
AB  - Arterial pressure, sodium excretion, urine output, and plasma atrial natriuretic
      peptide (ANP) concentrations were measured before, during, and after a 3-h i.v.
      infusion of arginine-vasopressin (vasopressin; 20 ng/kg/min) in conscious Doca
      salt hypertensive rats. Arterial pressure was 166 +/- 8 mm Hg before the infusion
      of vasopressin; in comparison, pressure was only 130 +/- 4 mm Hg 5 h after
      stopping the infusion. The fall in pressure after withdrawal of an equipressor
      dose of phenylephrine in hypertensive animals was much less. In sham normotensive
      rats, pressure did not fall below control levels after stopping either the
      vasopressin or phenylephrine infusion. Sodium excretion rates were higher during
      infusions of vasopressin than during phenylephrine infusions. However, the
      elevations observed during vasopressin were similar in the hypertensive (25.3 +/-
      4.9 mumol/kg/min) and normotensive (22.9 +/- 2.7 mumol/kg/min) groups. Urinary
      output increased to a greater extent in the hypertensive rats during the
      infusions of both vasopressin and phenylephrine, but the increases were similar
      for the 2 pressor agents. Plasma levels of ANP were elevated during the infusions
      of vasopressin in the normotensive rats, but not in hypertensive rats. The
      results indicate that the fall in pressure associated with cessation of a pressor
      dose of vasopressin appears specific to the hypertensive state, and relatively
      specific to vasopressin. This withdrawal-induced antihypertensive phenomenon
      (WAP) does not appear to be due solely to the preceding natriuresis and diuresis
      during the infusion of vasopressin. However, because the hypertensive animal may
      be more sensitive to a given degree of sodium loss, the possibility that the
      natriuresis could play a contributing or permissive role cannot be excluded.

PMID- 8261689
TI  - Carrier detection and prenatal diagnosis of hemoglobinopathies in Ontario.
AB  - The province of Ontario has a total population of approximately 10 million
      people, with approximately 20% being of African, Southeast Asian, East Indian,
      Mediterranean, or Middle Eastern ancestry in whom the gene frequency for
      hemoglobinopathies is relatively high. In 1989, the Ontario Ministry of Health
      funded the establishment of the Provincial Hemoglobinopathy DNA Diagnostic
      Laboratory located at the McMaster University Medical Centre in Hamilton,
      Ontario. The Laboratory provides DNA analysis to identify the globin gene
      mutations in carriers and affected individuals, and performs prenatal diagnosis
      for severe hemoglobinopathies. Annually, more than 400 patient samples are
      referred to the Laboratory for investigation, of which 25-35 are fetal samples
      from pregnancies at risk for either homozygous alpha-thalassemia, beta
      thalassemia major, or sickling disorders. We have detected more than 70 different
      globin gene mutations, including several mutations not previously reported in the
      literature. Here we present examples of the approaches used to detect globin gene
      mutations in a heterogeneous "at risk" population such as in Ontario, and discuss
      the impact of this service on patient care, genetic counselling, and the
      incidence of severe hemoglobinopathies in Ontario.

PMID- 8261690
TI  - Thromboxane synthase inhibition enhances furosemide-induced renal vasodilation.
AB  - The effects of furegrelate (a thromboxane synthase inhibitor), indomethacin, and
      the combination on urine volume (V), para-aminohippurate clearance (CPAH), and
      mean arterial pressure (MAP) before and after intravenous furosemide were
      examined in Sprague-Dawley rats. Prior to furosemide, none of the treatments
      changed MAP, V, or CPAH. Furosemide increased urine volume from 16 +/- 7 to 148
      +/- 25 microL.min-1. Concomitant administration of furegrelate or indomethacin
      did not affect furosemide-induced diuresis, but the combination of indomethacin,
      furegrelate, and furosemide caused increased diuresis (to 254 +/- 40
      microliters.min-1, p < 0.05, compared with furosemide alone). Furosemide alone or
      with the other drugs had no effect on mean arterial pressure. CPAH was increased
      from 3.0 +/- 0.4 to 4.6 +/- 0.8 ml.min-1.100g-1 (p < 0.05, n = 6) by furosemide,
      and to an even greater extent (6.7 +/- 0.8, n = 6) after pretreatment with
      furegrelate. Pretreatment with indomethacin alone or in combination with
      furegrelate abolished the furosemide-induced CPAH increment. Urine excretion of
      the prostacyclin hydrolysis product 6-ketoprostaglandin F1 alpha was increased by
      furosemide in the presence of furegrelate. Given that the transient renal
      vasodilation with furosemide is due to prostanoid precursor release, these
      results are consistent with redirection of arachidonate metabolism toward
      vasodilator prostaglandins by furegrelate.

PMID- 8261691
TI  - Immunohistochemical expression of mutant p53 oncogene in transitional mucosa
      adjacent to human colon cancer.
AB  - The purpose of this study was to analyze the expression of a mutant (MUT) p53
      oncogene protein in the mucosal crypts adjacent to a human colon cancer. Five 1
      cm mucosal segments were taken from the surgical specimens over a 5-cm distance
      from the tumor. Immunohistochemistry was performed using a monoclonal antibody
      (Ab3) to the MUT p53 and examination by light microscopy. The mean % labelling
      index (LI) of 10 crypts/cm segment was determined by image analysis. The LI for
      the entire crypt length for the first cm segment was 33.51 +/- 4.2 and for the
      second cm segment was 29.26 +/- 5.4 (p < 0.02). Due to the unequal distribution
      of the label within the crypt length, it was divided into halves so that the LI
      of these levels could be determined. The LI for the upper and lower crypt levels
      for the first cm segment were 28.67 +/- 3.2 and 78.23 +/- 4.6 (p < 0.01); for the
      second segment, the LI were 22.0 +/- 5.1 and 68.66 +/- 4.7 (p < 0.01). No
      expression of MUT p53 nuclear protein was noted distally at 3-5 cm. The
      localization of MUT p53 protein product to the crypt stem cell nucleus supports
      the contention that a malignant field change exists in the transitional mucosa
      adjacent to a human colon cancer.

PMID- 8261692
TI  - Antihypertensive effect and tolerability of felodipine extended release (ER)
      tablets in comparison with felodipine plain tablets (PT) and placebo in
      hypertensives on a diuretic. Canadian Study Group.
AB  - Antihypertensive efficacy and tolerability of felodipine extended release (ER)
      (o.d.), felodipine plain tablet (PT) (b.i.d.), and placebo were compared in mild
      to moderate hypertensives whose seated diastolic blood pressure (DBP) was > or =
      95 mm Hg while on hydrochlorothiazide 25 mg od. In addition to the diuretic,
      patients were randomised to felodipine ER 5 mg od (n = 50), PT 2.5 mg bid (n =
      50), or placebo (n = 48) for 6 weeks, with clinic visits every 2 weeks. If seated
      DBP was > or = 90 mm Hg at any visit, daily dosage of felodipine was doubled to a
      maximum of 20 mg. The mean difference between ER and placebo was 5.1 mm Hg (p =
      0.003); for PT vs. placebo the difference was 5.3 mm Hg (p = 0.002). Seated
      systolic blood pressure (SBP) was reduced by a mean difference of 6.8 mm Hg in
      the felodipine PT group compared with placebo (p = 0.03). Fourteen patients were
      withdrawn: 4 from the placebo group, 4 from the felodipine ER group, and 6 from
      the felodipine PT group. The most commonly reported adverse event was peripheral
      edema. In patients not adequately controlled on diuretic alone, felodipine ER
      o.d. and felodipine PT b.i.d. were superior to placebo in reducing seated DBP.

PMID- 8261693
TI  - Parathyroid hormone-related peptide.
AB  - Parathyroid hormone-related peptide (PTHRP) was discovered through its ability to
      cause parathyroid hormone (PTH)-like effects in malignancy-associated
      hypercalcemia (MAH). It shares limited amino-terminal sequence homology with PTH
      and can thus interact with PTH receptors. It was originally isolated, cloned, and
      sequenced from tumors of patients with MAH. The human PTHRP gene is complex and
      can generate 3 peptide isoforms of 139, 141, and 173 amino acids. The gene
      encoding PTHRP in other species is somewhat simpler and generally results in only
      a single isoform; however, there is marked interspecies amino acid sequence
      homology in the protein product up to residue 111. PTH and PTHRP genes have
      similar structural organizations and it is believed that these 2 genes have a
      common ancestral origin and may have arisen through an ancient gene duplication.
      There are now several region specific radioimmunoassays, as well as
      immunoradiometric assays, which have been developed and which have all
      demonstrated elevated circulating levels of PTHRP in patients with MAH. PTHRP is
      expressed in a wide variety of tissues and, in addition to its classical PTH-like
      activities, it may have a local or systemic role in calcium regulation in the
      fetus and perhaps in the neonate. It may also act locally as a smooth muscle
      relaxant and a vasorelaxant. Its local role in some fetal tissues and in
      keratinocytes may take the form of a regulator of cell growth and/or
      differentiation. Thus when antisense RNA technology was used to inhibit
      endogenous PTHRP production in an established human keratinocyte cell line, PTHRP
      was found to inhibit growth and enhance differentiation. Irrespective of its
      precise normal role however, PTHRP provides a potential therapeutic target in MAH
      and, with improved methods of detection, may also be useful as a tumor marker.

PMID- 8261694
TI  - [MR findings of the pyramidal tract in amyotrophic lateral sclerosis].
AB  - MR imaging using the conventional spin each technique along with diffusion
      weighted imaging and water-fat imaging was performed in 16 patients with
      amyotrophic lateral sclerosis (ALS), 20 normal subjects, and 113 controls with
      other neurological disorders. Diffusion weighted images in the patients with ALS
      and the controls disclosed a high signal band from the subcortical area to the
      medullary pyramids. The high signal band on the diffusion weighted images
      corresponded to the pyramidal tract in the anatomical atlas described by
      Talairach. The T1- and T2-relaxation times, proton density, diffusion coefficient
      and diffusion anisotropy were measured at the points where high signal bands
      appeared on the diffusion weighted images. The T2-weighted images revealed high
      signal areas on the posterior limbs of the internal capsules in all the patients
      with ALS, 60% of the normal subjects, and 73% of the disease controls. The T1
      weighted images disclosed high signal areas on the posterior limbs in 62% of the
      patients with ALS, but not in any of the normal subjects and the disease
      controls. The proton weighted images disclosed high signal areas on the posterior
      limbs in all the patients with ALS and 5% of the disease controls, but not in any
      of the normal subjects. Analysis of diffusion weighted images revealed no
      significant difference between the patients with ALS and the normal subjects in
      diffusion coefficient and diffusion anisotropy on the posterior limbs.
      Measurement of MR parameters (T1- and T2-relaxation times and proton density)
      showed that the proton density at the posterior limbs increased in ALS. Water-fat
      images using the method of Dixon revealed abnormal signals in the water images.
      These signal abnormalities were more prominent in the internal capsule than in
      the medullary pyramids. Our findings confirm that there is an increase in water
      molecules that have normal diffusion coefficient and diffusion anisotropy values
      in patients with ALS.

PMID- 8261695
TI  - [Serial observations of respiratory function in disabled patients with myotonic
      dystrophy].
AB  - Serial assessments of respiratory function were performed over 1 to 8 years in 12
      patients with myotonic dystrophy. Respiratory parameters included vital capacity
      (percentage of predicted value; %VC) and one-second forced expiratory volume
      (percentage of predicted value; FEV1.0%) on spirogram and arterial blood gases at
      rest. The patients who had no primary respiratory disease were ranged in age from
      31 to 61 years, with an average age of 47 years, and their mean duration of
      illness was 20 years. All the subjects were severely disabled; only two patients
      were able to walk with assistance, but other ten patients were confined to a
      wheelchair. During the observation period, five patients died; 4 due to
      respiratory failure and one cardiac and respiratory failure. The following
      results were obtained: (1) almost all the patients showed a reduction in %VC, the
      severity of which was gradually progressed with advancing age. A significant
      negative correlation was observed between %VC and duration of illness. (2) PaCO2
      was negatively correlated with %VC, while the relationship between PaO2 and %VC
      appeared to be a significant positive correlation. Chronic alveolar
      hypoventilation (hypercapnia and hypoxemia) was particularly likely when vital
      capacity (VC) was less than 40% of the predicted value in the patients. This
      study indicates that a reduction of VC plays an important role in development of
      respiratory failure in myotonic dystrophy and serial measurements of VC and
      arterial blood gases are useful in the detection of it.

PMID- 8261696
TI  - [Warfarin therapy for secondary prevention of cardioembolic stroke with
      nonvalvular atrial fibrillation--a retrospective study].
AB  - In order to evaluate the efficacy of warfarin for the secondary prevention of
      cardioembolic stroke due to nonvalvular atrial fibrillation (NVAF), we
      retrospectively investigated the frequencies of recurrent brain embolism and
      hemorrhagic complications in 68 subjects (62 +/- 9 years old, 54 men and 14
      women), who had experienced at least one cardioembolic stroke prior to the study
      period. The follow-up period was 39 +/- 27 months. Paroxysmal and persistent
      atrial fibrillation were seen in 37 and 31 subjects, respectively. We assigned
      the subjects to three subgroups according to types of the events during the
      follow-up; recurrence group, hemorrhage group, and non-accident group.
      Prothrombin time (international normalized ratio, INR) was assessed as mean value
      during the follow-up period. The prothrombin time at the time of recurrence and
      hemorrhagic complication was also taken into consideration for data analysis.
      Recurrent brain embolism was observed in three patients (1.4%/yr). Major bleeding
      occurred in 12 patients (5.5%/yr) and three of them were fatal (subarachnoid
      hemorrhage, brain hemorrhage, and acute subdural hematoma). The mean value of INR
      in the hemorrhage group (3.0) was higher than that in the recurrence group (2.2)
      and in the non-accident group (2.3) (p < 0.001, vs. non-accident group). The
      lowest mean value of INR in the hemorrhage group was 2.5. The prothrombin time in
      the recurrence group did not differ from that in the non-accident group. The
      death rate in the hemorrhage group (4/12, 33.3%) was higher than those in the
      recurrence group (0) and in the non-accident group (4/53, 7.5%) (p < 0.01, vs.
      non-accident group).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261697
TI  - [The effect of nasal IPPV on patients with respiratory failure during sleep due
      to Duchenne muscular dystrophy].
AB  - In order to investigate respiratory failure during sleep in patients with
      Duchenne muscular dystrophy (DMD), overnight arterial oxygen saturation (SaO2)
      and end-tidal CO2 (EtCO2) monitoring by capnographoximeter was performed. We
      supposed that average of EtCO2 over 60 mmHg documented by continuous overnight
      capnograph study indicated the need for introducing nocturnal respiratory
      assistance. Accordingly, four patients who showed EtCO2 over 60 mmHg were
      initiated to treat with nocturnal nasal intermittent positive pressure
      ventilation (NIPPV). The first ventilator settings were adjusted for patient
      comfort and to attain near normal arterial blood gas values while the patients
      were awake on NIPPV. After the patients were able to tolerate NIPPV for the whole
      night, overnight recording of SaO2 and EtCO2 on nocturnal NIPPV were made to
      assure the adequacy of ventilation and to provide basis for adjusting ventilator
      settings. Subsequently, appropriate nocturnal NIPPV could normalize overnight
      SaO2 and EtCO2, improve daytime arterial PO2 and PCO2, and reverse symptoms of
      chronic alveolar hypoventilation in these patients. According to further decline
      in pulmonary function, efficacy of NIPPV must be checked periodically by
      overnight monitoring, and ventilator resettings should be done if necessary. We
      believe that early awareness and appropriate management of respiratory failure
      during sleep by NIPPV are important to postpone tracheostomy for patients with
      DMD.

PMID- 8261698
TI  - [Free amino acids and activities of folate-derivative converting enzymes in
      nervous system of rats administered with beta, beta'-iminodipropionitrile].
AB  - Swelling of proximal axon is a morphological similarity between patients with
      amyotrophic lateral sclerosis (ALS) and beta, beta'-iminodipropionitrile (IDPN)
      injected animals. In order to investigate whether these two states have something
      in common biochemically with each other, we measured free amino acids (FAAs) and
      activities of folate-derivative converting enzymes which participate in the
      metabolic turnover of the folate cycle. Thirty male Wistar rats weighing about
      125 g were administered intraperitoneally with 2 g/kg of IDPN. These rats and 10
      control rats injected with physiological saline were sacrificed 1, 3 and 6 weeks
      after injection. Subsequently organs were immediately removed and stored at -80
      degrees C until analyzed. FAAs were quantitated by a JLC-6AH amino acid analyzer,
      and activities of the enzymes were measured by established methods. Changes in
      FAAs were detected not only in the central and peripheral nervous systems, but
      also in the other tissues examined, suggesting diverse action of IDPN. Among the
      various changes, elevation of taurine content in the cerebrum and spinal cord
      seems to be important, because the same alteration has been reported in the
      central nervous system (CNS) of ALS patients. In relation to the increase in
      taurine, metabolic slowing-down of the folate cycle which has been reported in
      ALS was suggested from reduced activity of N5,N10-methylenetetrahydrofolate
      reductase (MTR), one of the three enzymes of this metabolic cycle.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8261699
TI  - [The relationship of periventricular hyperintensity with cerebral blood flow and
      cerebrovascular reserve capacity in asymptomatic individuals].
AB  - Although periventricular hyperintensity (PVH) is frequently detected in elderly
      persons by magnetic resonance imaging (MRI), the relationship of such lesions
      with cerebral blood flow (CBF) and cerebrovascular reserve capacity has never
      been determined. We used acetazolamide-enhanced xenon-133 CBF and MRI to study 28
      subjects with one or more cerebrovascular risk factors but with no neurological
      symptoms. According to MRI examinations on the transaxial slice of the body of
      the lateral ventricle, 10 subjects had no PVH (group O), 7 a partial PVH (group
      I), 6 a continuous PVH (group II), and 5 a confluent PVH which spreads over a
      wide area of the white matter (group III). There was no relationship between the
      severity of PVH and the resting cortical CBF (F = 2.7). However, the severity of
      PVH showed significant negative relationships with the acetazolamide-enhanced CBF
      (F = 9.5; p < 0.01), and the absolute increase of CBF from the resting state to
      the acetazolamide challenge (F = 5.1; p < 0.01). Our data suggest the importance
      of hemodynamic factors and the compensatory vasodilation in the pathogenesis of
      PVH in asymptomatic individuals.

PMID- 8261700
TI  - [Bilateral internal carotid artery stenoses in a patient with meningovascular
      neurosyphilis].
AB  - We report a 37-year-old man with cerebral infarction due to meningovascular
      neurosyphilis. He developed right hemiplegia and motor aphasia preceded by left
      retroorbital pain lasting a month. Bilateral tonic pupils were also observed.
      Magnetic resonance imaging (MRI) disclosed cerebral infarction in the
      distribution of perforating branches of the left middle cerebral artery. Abnormal
      enhancement was absent in the meninges on T1-weighted MRI examination. SPECT
      study with I-123 iodoamphetamine showed decreased perfusion in the area of the
      left middle cerebral artery on early phase. A delayed SPECT 4 hour later
      demonstrated redistribution of the cerebral blood flow in the area of its
      cortical branches. On cerebral angiograms, marked stenoses were disclosed at the
      supraclinoid segments of the bilateral internal carotid arteries as well as the
      M1 segment of the left middle cerebral artery. These stenoses were associated
      with increased collateral circulations on the left side. Atherosclerosis was not
      apparent, on angiography. The cerebrospinal fluid (CSF) showed pleocytosis and
      positive TPHA. The CSF/serum ratio of TPHA was 1/16. Oligoclonal IgG band was
      present in the CSF. CSF IgG index was elevated. These findings were consistent
      with meningovascular neurosyphilis. Causes of angiitis other than syphilis were
      excluded. A test for antibodies against human immunodeficiency virus was
      negative. The clinical course of his recovery was similar to that in patients
      with atherosclerotic thrombosis. The stenosis of the right internal carotid
      artery demonstrated by angiography could not be expected from the clinical
      manifestations and SPECT study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261701
TI  - [Chronic herpes simplex encephalitis initially presenting with persistent
      myoclonus].
AB  - A 59-year-old female patient with atypical chronic herpes simplex encephalitis
      was reported. Initial symptom was persistent myoclonus involving the trunk and
      limb muscles, and later lateral gaze palsy to the left side, cerebellar ataxia,
      consciousness disturbance and other brainstem symptoms including absence of
      corneal and gag reflex and vocal cord palsy developed. The patient was
      successfully treated with high dose of acyclovir. Electroencephalogram was normal
      in the initial stage but later showed diffuse slow waves. Although CT scan and
      MRI showed no abnormal finding in the cerebral cortex, brainstem lesion was
      observed on PD weighted image of MRI. Lumbar puncture yielded a clear
      cerebrospinal fluid, with slightly elevated protein, increased lymphocytes, and
      elevated titer of herpes simplex virus type I. The serological data, albumin
      ratio (10.3), antibody index (12.3) and antibody ratio (7.1) were consistent with
      herpes simplex encephalitis. Ten days' administration of acyclovir, 1,200 mg a
      day and repeated three times, was prominently effective for the myoclonus and
      consciousness disturbance. A diagnosis of chronic herpes simplex encephalitis
      initially presenting with brainstem encephalitis was made. Judging from the
      clinical and EEG findings, the brainstem lesion was initially thought to be a
      cause of myoclonus in this case. However, somatosensory evoked potential (SPE) of
      both upper and lower extremities revealed enlarged amplitude (giant SEP), and
      long loop reflex was enhanced (C-reflex) on the left. Giant SEP and C-reflex
      imply cerebral cortex as the origin of the myoclonus. Brainstem inflammatory
      lesion might have involved the ascending inhibitory system, thus disinhibiting
      the cortical sensorimotor area and causing cortical myoclonus.

PMID- 8261702
TI  - [Distal myopathy with rimmed vacuoles and sudden death--report of two siblings].
AB  - We describe two siblings with distal myopathy with rimmed vacuoles, who died
      suddenly presumably due to fatal arrhythmia. Case 1. A 26-year-old man with a 4
      year-history of progressive muscle weakness and wasting was hospitalized in
      April, 1989. The family history showed that his younger brother had the same
      disease, but his parents, not consanguineous, and other family members had no
      neuromuscular diseases. On admission, neurologic examination showed muscle
      weakness and atrophy in the distal portions of four extremities. No myotonia or
      fasciculation was present. The deep tendon reflexes were absent except diminished
      bilateral PTR. Sensation and co-ordination were normal. The creatinine kinase
      (CK) level was moderately elevated to 691 IU/l, and the aldolase mildly to 6.9
      IU/l. Normal laboratory values included serum electrolytes, glucose and thyroid
      function study. An ischemic forearm exercise test revealed a normal rise in serum
      lactate and pyruvate concentrations. The glucose response after glucagon was
      normal in the fasting state. An electrocardiogram and chest film were normal. An
      electromyogram revealed myopathic changes with mild neuropathic changes,
      including positive sharp waves and fibrillation potentials at rest. The muscle
      biopsy specimen from the left anterior tibial muscle showed scattered fibers with
      rimmed vacuoles and moderate variation in fiber size. Neither fiber necrosis nor
      inflammatory cellular infiltration was seen. Regenerating fiber was not present.
      An electron microscopic examination showed numerous lamellar bodies of various
      size. Nerve biopsy was normal. He was diagnosed as having distal myopathy with
      rimmed vacuoles. Muscle weakness progressed gradually over the next two years,
      but his general condition was good. He asked to receive the corticosteroid
      therapy, and rehospitalized.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261703
TI  - [Proximal lower motor neuron syndrome associated with serum antibodies to asialo
      GM1, GM1 and LM1].
AB  - A 31-year-old man had noticed slowly progressive weakness in his right upper limb
      girdle. On admission at age 32, fasciculation and muscle atrophy were observed in
      the right pectoralis major muscle. There was mild muscle weakness in the right
      triceps brachii muscle. The deep tendon reflexes were normal and the pathologic
      reflexes were absent. Sensory and autonomic nerve functions were intact. Needle
      EMG showed fibrillation potentials and positive sharp waves in the right
      pectoralis major, infraspinatus, extensor carpi radialis, extensor digitorum
      muscles, the bilateral sternocleidomastoideus and triceps brachii muscles. Motor
      nerve conduction studies revealed normal conduction velocities and distal
      latencies as well as no evidence of conduction block or abnormal temporal
      dispersion. Serum immunoelectrophoresis failed to detect an M protein. Thin-layer
      chromatography with immunostaining revealed that the serum contained auto
      antibodies which reacted with asialo-GM1, GM1 and LM1. This case must belong to
      "proximal lower motor neuron syndrome" proposed by Pestronk et al.

PMID- 8261704
TI  - [A case of cryptococcal meningitis in an HTLV-1 carrier].
AB  - We report a case of 73-year-old male HTLV-I carrier with cryptococcal meningitis.
      The patient, who was born in Taiwan, has raised golden pheasants for ten years
      and bantams for five years. Antibody to HIV was negative. Flow cytometric study
      of the peripheral lymphocytes showed reduced CD4+CD45RA+ (naive cells) and
      increased CD4+CD45RO+ (memory cells), CD3+CD25+ and CD3+ HLA-DR(DR)+ cells.
      Lymphocyte responses to phytohemagglutinin and concanavalin A were depressed.
      Cerebrospinal fluid (CSF) cells and serum and CSF antigen to cryptococcal
      neoformans were decreased by therapy with fluconazole and flucytosine. Although
      the naive, memory and CD3+DR+ cell abnormalities showed no change, the
      CD45RA/CD45RO ratio and CD3+CD25+ level tended to improve. Opportunistic
      infections such as cryptococcal meningitis may be induced by severe decreases in
      naive cells and increases in memory cells in HTLV-I carriers.

PMID- 8261705
TI  - [A case of asymptomatic common carotid artery occlusion with the persistent
      proatlantal intersegmental artery].
AB  - A case of asymptomatic common carotid artery occlusion with direct
      vertebrocarotid anastomosis (proatlantal intersegmental artery) in a 70-year-old
      male is reported. Despite the acquired left common carotid artery occlusion,
      there was no demonstrable neurologic deficits that would occur by the involvement
      of the area supplied by the occluded carotid system. Cerebral angiography
      revealed, in addition to efficient collateral circulation from the contralateral
      carotid system through the anterior communicating artery, a collateral channel
      from the left vertebral artery to the ipsilateral external carotid artery via the
      proatlantal intersegmental artery. These collateral circulations were indicated
      to be important in prevention of possible grave neurologic consequences. The
      proatlantal intersegmental artery, though rarely visualized by ordinary cerebral
      angiographic procedures, was thus demonstrated to be capable of serving as a
      collateral channel of potential usefulness in the event of severe intracranial
      hemodynamic alterations, including acquired common carotid artery occlusion.

PMID- 8261706
TI  - [A sporadic case of late onset familial amyloidotic polyneuropathy preceded by
      cardiac involvement].
AB  - We report a 65-year-old man with amyloidotic polyneuropathy, who first suffered
      from heart failure at the age of 57, 3 years before the onset of neurological
      symptoms. He had no obvious family history. We analysed the transthyretin gene of
      the patient and 6 asymptomatic family members using polymerase chain reaction
      (PCR). The single amino acid substitution of a methionine for valine at position
      30, which is a common mutation of Japanese type I FAP patients, was found from
      the patient and his sister of 47 years. Though Type I FAP patients often have
      cardiac conduction block, they rarely have signs of heart failure until the end
      stage of the disease. This is the first report of Type I FAP with severe
      myocardial involvement, in which TTR mutation at position 30 was confirmed. The
      result revealed the clinical variation of Type I FAP.

PMID- 8261707
TI  - [A case of juvenile onset ataxia with dystonia, myoclonus, sensorineural hearing
      loss and mental retardation].
AB  - A 35-year-old female was reported who presented early onset and slowly
      progressive ataxia and retrocollis which appeared at the age of nine. On
      admission, neurological examination revealed cerebellar ataxia, dystonia of the
      neck and the right arm, myoclonus of the neck and the shoulder, slight mental
      retardation, supranuclear upper gaze palsy, and sensorineural hearing loss.
      Laboratory examination showed high serum CK activity. Electromyography and muscle
      biopsy findings suggested slight muscular involvement. CSF level of HVA and 5
      HIAA were reduced. MRI demonstrated marked cerebellar atrophy and slight atrophy
      of the brain stem. To our knowledge, the characteristic combination of the
      neurological sign in this case has not been reported. This case was compared with
      EOCA (early onset cerebellar ataxia with retained tendon reflexes) and other
      juvenile onset cerebellar ataxia and dystonia.

PMID- 8261708
TI  - [Myelopathy with uveitis in association with HTLV-I mimicking neuro-Behcet's
      disease].
AB  - A 31-year-old woman was referred to our hospital because of recurrent uveitis
      with oral aphthae for four years, and subacute double incontinence with spastic
      paraparesis under a clinical diagnosis of neuro-Behcet's disease. She was found
      to have high titers of anti-HTLV-I antibody in the serum, the cerebrospinal fluid
      and the aqueous humor, and a diagnosis of HTLV-I associated myelopathy (HAM) with
      HTLV-I uveitis was confirmed. The neurological symptoms improved transiently with
      prednisolone therapy. HTLV-I uveitis is known sometimes complicated with HAM. The
      neurological features together with uveitis in the present case were allied to
      those of neuro-Behcet's disease. Therefore, HAM with uveitis should be
      differentiated from neuro-Behcet's disease.

PMID- 8261709
TI  - [Cytomegalovirus ascending myelitis in an immunocompetent adult].
AB  - A 32-year-old man was hospitalized because of tetraparesis, sensory loss below
      cervical line, and urinary bladder dysfunction. Two months prior to this
      admission, he had suffered from cytomegalovirus (CMV) mononucleosis characterized
      by fever, presence of atypical lymphocytes and high serum titers of CMV-IgG/IgM
      antibodies. A lumbar puncture yielded clear fluid with 104 leukocytes
      (predominantly mononuclear cells)/mm3; protein, 102 mg/dl; and CMV-IgG antibodies
      (EIA), 1210. CMV antibody serum/CSF ratio was decreased to 2.08 (normal range >
      or = 20), indicating intrathecal production of CMV antibodies. T2-weighted images
      of spinal MRI showed diffuse high signal intensity lesions throughout the cord
      below C3 vertebral body level. A diagnosis of ascending myelitis secondary to CMV
      infection was made. Methylprednisolone pulse therapy led to some improvement in
      his neurologic dysfunctions. This is the first case report of CMV ascending
      myelitis in a previously healthy adult.

PMID- 8261710
TI  - Relevance of pharmacokinetic studies in volunteers.

PMID- 8261711
TI  - Cefpirome clinical pharmacokinetics.
AB  - Cefpirome is a new cephalosporin that exhibits similar in vitro potency to
      ceftazidime against Gram-negative organisms but has significantly greater in
      vitro potency against Gram-positive organisms. Cefpirome differs from cefotaxime
      in that a 3'-pyridinium moiety replaces the acetoxy moiety of cefotaxime. This
      structural change imparts greater beta-lactamase stability, increases the ability
      to penetrate the outer membrane of Gram-negative bacteria, and enhances activity
      against Gram-positive organisms. The pharmacokinetic properties of cefpirome are
      typical of cephalosporins. The drug can be administered by intravenous or
      intramuscular injection, but is not well absorbed after oral administration.
      Bioavailability following intramuscular injection exceeds 90%. Cefpirome exhibits
      low protein binding (approximately 10%) and has a volume of distribution similar
      to extracellular fluid volume. Cefpirome penetrates the prostate gland, lung,
      blister fluid, cerebrospinal fluid and peritoneal fluid, reaching concentrations
      that are similar to those achieved by other later generation cephalosporins.
      Approximately 80% of an intravenous dose is eliminated unchanged in the urine. No
      active metabolites of cefpirome have been identified. The elimination half-life
      of cefpirome is approximately 2 hours. Elimination appears to be primarily by
      glomerular filtration since the total clearance of cefpirome is approximately
      equal to creatinine clearance. The time during which drug concentrations exceed
      the minimum inhibitory concentration (MIC) represents the most clinically
      important pharmacodynamic parameter for beta-lactam agents. When cefpirome is
      administered at a dosage of 2g every 12 hours to patients without renal
      insufficiency [creatinine clearance 70 ml/min (4.2 L/h)], drug concentrations
      continuously remain above the MIC for pathogens with MIC values of < or = 2
      micrograms/ml. With this dosage regimen, drug concentrations will be above the
      MIC for a pathogen with an MIC of 4 micrograms/ml for 80% of the dosage interval.
      The time above MIC for pathogens with an MIC of 8 micrograms/ml is only 60% of
      the dosage interval.

PMID- 8261712
TI  - Enalapril clinical pharmacokinetics and pharmacokinetic-pharmacodynamic
      relationships. An overview.
AB  - The conventional pharmacokinetic profile of the angiotensin converting enzyme
      (ACE) inhibitor, enalapril, is a lipid-soluble and relatively inactive prodrug
      with good oral absorption (60 to 70%), a rapid peak plasma concentration (1 hour)
      and rapid clearance (undetectable by 4 hours) by de-esterification in the liver
      to a primary active diacid metabolite, enalaprilat. Peak plasma enalaprilat
      concentrations occur 2 to 4 hours after oral enalapril administration.
      Elimination thereafter is biphasic, with an initial phase which reflects renal
      filtration (elimination half-life 2 to 6 hours) and a subsequent prolonged phase
      (elimination half-life 36 hours), the latter representing equilibration of drug
      from tissue distribution sites. The prolonged phase does not contribute to drug
      accumulation on repeated administration but is thought to be of pharmacological
      significance in mediating drug effects. Renal impairment [particularly creatinine
      clearance < 20 ml/min (< 1.2 L/h)] results in significant accumulation of
      enalaprilat and necessitates dosage reduction. Accumulation is probably the cause
      of reduced elimination in healthy elderly individuals and in patients with
      concomitant diabetes, hypertension and heart failure. Conventional
      pharmacokinetic approaches have recently been extended by more detailed
      descriptions of the nonlinear binding of enalaprilat to ACE in plasma and tissue
      sites. As a result of these new approaches, there have been significant
      improvements in the characterisation of concentration-time profiles for single
      dose administration and the translation to steady-state. Such improvements have
      further importance for the accurate integration of the pharmacokinetic and
      pharmacodynamic responses to enalapril(at) in a concentration-effect
      model.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261713
TI  - Hypoxia, arterial pH and theophylline disposition.
AB  - Theophylline is a bronchodilator used extensively in the management of
      obstructive pulmonary disease. Factors implicated in altered theophylline
      clearance include smoking, age, concomitant drug intake, liver disease and left
      ventricular heart failure. However, evidence now suggests that theophylline
      clearance may be altered by changes in severity of the pulmonary obstruction,
      hypoxia and variation in arterial pH. The in vitro disposition of theophylline
      has been evaluated in isolated rat livers and mouse hepatocytes. In vivo studies
      have assessed the metabolism of theophylline under hypoxia in rats, rabbits and
      dogs. In isolated mouse hepatocytes and rat livers, low oxygen concentrations
      resulted in higher theophylline concentrations, a longer elimination half-life
      and a decrease in the production of the metabolite 1,3-dimethyl uric acid,
      suggesting impaired metabolism of theophylline. In rabbits, hypoxia, hypercapnia
      and respiratory acidosis decreased total body clearance and increased plasma
      theophylline concentrations. On the other hand, experiments involving dogs showed
      no significant changes in theophylline concentrations or pharmacokinetic
      parameters with hypoxia. At present, animal studies remain inconclusive. This can
      be attributed to the use of different animal models and variations in study
      methodology, including the extent and duration of hypoxia and acidaemia,
      concurrent acid-base disorders such as hypercapnia, as well as the severity of
      pulmonary obstruction. Human studies assessing alterations in theophylline
      disposition secondary to the hypoxia present in pulmonary disease are few and
      include mostly case reports and observational studies. There is evidence
      suggesting decreased theophylline clearance and protein binding during acute
      illness and some consensus can be achieved using case reports and controlled
      studies. There is additional evidence that drug clearance decreases with age and
      that elderly patients may have a decreased theophylline clearance at baseline.
      However, the most obvious markers appear to be the severity of pulmonary disease
      and the rate of change in the patient's condition. Caution should be exercised
      when administering theophylline to elderly patients with chronic obstructive
      pulmonary disease presenting with acute exacerbations of a concomitant
      respiratory illness, as these patients appear to be most likely to exhibit
      altered theophylline metabolism. Therefore, they would be at increased risk for
      toxicity should conventional dosages be used during an acute respiratory event.

PMID- 8261715
TI  - Pharmacokinetic optimisation of oral antifungal therapy.
AB  - The range of oral antifungal therapy has been expanded recently by the
      introduction of itraconazole, and terbinafine. These agents have a broader
      spectrum of activity than griseofulvin and flucytosine, and induce less liver
      toxicity than ketoconazole. Treatment with these agents may be optimised by
      application of pharmacokinetic principles. Griseofulvin, ketoconazole and
      itraconazole should be administered with food to ensure adequate absorption.
      Maximal absorption of griseofulvin is achieved by administration of the drug as a
      solid solution in polyethylene glycol. Absorption of azole antifungal agents is
      impaired by high gastric pH, which is observed in some patients with acquired
      immunodeficiency syndrome. It is also impaired by frequent vomiting, which
      commonly occurs in patients with neutropenia. Furthermore, antacids, H2
      antagonists and sucralfate interfere with absorption of ketoconazole. The newer
      oral antifungals are more slowly eliminated and associated with less pronounced
      drug interactions than ketoconazole. As with ketoconazole, itraconazole and
      fluconazole influence cyclosporin metabolism. These effects are of clinical
      relevance and necessitate cyclosporin dosage reduction. However, the cyclosporin
      dosage reduction required during coadministration of itraconazole and fluconazole
      (50 to 55%) is less than that required when ketoconazole is concomitantly
      administered (85%). Monitoring of cyclosporin concentrations during
      coadministration with these agents is necessary to avoid nephrotoxicity. Drug
      monitoring is also advisable when phenytoin, carbamazepine or rifampicin
      (rifampin) are administered concomitantly with azoles, due to a mutual influence
      on drug metabolism. The antifungal activity of itraconazole is not related
      exclusively to free drug concentrations. Therefore, the low protein binding of
      fluconazole does not place this agent at an advantage over itraconazole in the
      treatment of fungal meningitis. However, terbinafine may be superior to
      itraconazole for the treatment of tinea unguium, another recalcitrant fungal
      disease, because terbinafine more rapidly penetrates the nail plate. During
      repeated use, itraconazole concentrations increase slowly in the nail plate.
      Steady-state concentrations are reached in the stratum corneum only after several
      weeks' administration. Following cessation of treatment, terbinafine,
      itraconazole and ketoconazole concentrations in keratinised tissues decline
      slowly. This allows a short duration of drug treatment. Some clinical trials
      suggest that low concentrations of flucytosine, griseofulvin and itraconazole are
      associated with treatment failure. Flucytosine-induced myelotoxicity also appears
      to be concentration dependent. This adverse reaction may be caused by
      fluorouracil (which is produced by metabolism of flucytosine by enterobacillary
      flora in the gut) rather than by the parent compound.

PMID- 8261716
TI  - Articular pharmacokinetics of protein-bound antirheumatic agents.
AB  - By what mechanism do nonsteroidal anti-inflammatory drugs (NSAIDs) move from
      plasma into synovial fluid and back, and how does binding to plasma albumin in
      vitro relate to articular transport in vivo? To evaluate these issues, concurrent
      plasma and synovial fluid data of 8 different NSAIDs from 10 single-dose trials
      were analysed by a simple compartmental model incorporating intra-articular
      volume, synovial plasma flow rates and protein transport. All pharmacological and
      physiological data were taken from published studies of chronic knee effusions in
      patients with rheumatoid arthritis. The analysis shows that these protein-bound
      NSAIDs readily leave the vasculature and enter synovial fluid during each transit
      of synovial microvessels. The mean rate of transport, 0.23 min-1, is consistent
      with passive diffusion at rates far in excess of those attributable to movement
      of albumin-bound drug or of the small, free-drug fraction found by equilibrium
      dialysis. These findings are explained by association and dissociation of NSAIDs
      and albumin that occur far more rapidly than vascular transit. Ongoing
      dissociation makes bound drug available for transvascular exchange and thereby
      diminishes the pharmacokinetic significance of binding data obtained in vitro.

PMID- 8261717
TI  - A model for the nation.

PMID- 8261718
TI  - The state of the child.

PMID- 8261719
TI  - Lessons from health trends for systems of child health care.

PMID- 8261720
TI  - Children's access to health coverage. The upside-down house.

PMID- 8261721
TI  - Continuum of care system development.

PMID- 8261714
TI  - Individual variation in first-pass metabolism.
AB  - Individual variation in pharmacokinetics has long been recognised. This
      variability is extremely pronounced in drugs that undergo extensive first-pass
      metabolism. Drug concentrations obtained from individuals given the same dose
      could range several-fold, even in young healthy volunteers. In addition to the
      liver, which is the major organ for drug and xenobiotic metabolism, the gut and
      the lung can contribute significantly to variability in first-pass metabolism.
      Unfortunately, the contributions of the latter 2 organs are difficult to quantify
      because conventional in vivo methods for quantifying first-pass metabolism are
      not sufficiently specific. Drugs that are mainly eliminated by phase II
      metabolism (e.g. estrogens and progestogens, morphine, etc.) undergo significant
      first-pass gut metabolism. This is because the gut is rich in conjugating
      enzymes. The role of the lung in first-pass metabolism is not clear, although it
      is quite avid in binding basic drugs such as lidocaine (lignocaine), propranolol,
      etc. Factors such as age, gender, disease states, enzyme induction and
      inhibition, genetic polymorphism and food effects have been implicated in causing
      variability in pharmacokinetics of drugs that undergo extensive first-pass
      metabolism. Of various factors considered, age and gender make the least evident
      contributions, whereas genetic polymorphism, enzymatic changes due to induction
      or inhibition, and the effects of food are major contributors to the variability
      in first-pass metabolism. These factors can easily cause several-fold variations.
      Polymorphic disposition of imipramine and propafenone, an increase in verapamil
      first-pass metabolism by rifampicin (rifampin), and the effects of food on
      propranolol, metoprolol and propafenone, are typical examples. Unfortunately, the
      contributions of these factors towards variability are unpredictable and tend to
      be drug-dependent. A change in steady-state clearance of a drug can sometimes be
      exacerbated when first-pass metabolism and systemic clearance of a drug are
      simultaneously altered. Therefore, an understanding of the source of variability
      is the key to the optimisation of therapy.

PMID- 8261722
TI  - A public/private partnership providing an integrated system of health care for
      children. The Children's Medical Services Program of Florida.

PMID- 8261723
TI  - The continuum of care program.

PMID- 8261724
TI  - One parent's perspective.

PMID- 8261725
TI  - Building a responsible system of care.

PMID- 8261726
TI  - Early detection and treatment of sexually transmitted disease in pregnant
      adolescents of low socioeconomic status.
AB  - This study evaluated the prevalence of sexually transmitted disease (STD) in
      adolescents presenting to a primary pediatric care clinic (PPCC) for the
      diagnosis of pregnancy and our ability to eradicate identified infections. We
      followed 168 pregnant adolescents of low socioeconomic status from their original
      pregnancy diagnosis until their first prenatal clinic visit. We collected
      screening cervical cultures for Neisseria gonorrhoeae and Chlamydia trachomatis
      by completing a pelvic examination on 91 patients at our PPCC. At the PPCC visit,
      29% were positive for gonorrhea, chlamydia, or both. Screening tests for these
      infections were collected on all patients at the initial prenatal clinic visit.
      The risk for presenting to the prenatal clinic with a STD was significantly
      greater in patients not screened and treated for STD at the PPCC. Average delay
      from diagnosis to first prenatal clinic visit was 35.7 days. Thus, in this
      adolescent population, primary care providers are missing an important
      therapeutic opportunity by failing to identify and treat STD at initial diagnosis
      of pregnancy.

PMID- 8261727
TI  - Rett syndrome. An update and review for the primary pediatrician.
AB  - Rett syndrome is a common developmental-neurologic disorder that has been
      reported almost exclusively in females. Recent work has improved recognition of
      this condition and helped to clarify the management of this disorder for affected
      individuals. The primary-care physician can become a major source of support and
      advocacy for the family of a girl with Rett syndrome. Many other resources are
      available to the primary care giver and the families of children with Rett
      syndrome; these may help to provide early diagnosis, psychological support, and
      preventive medical care for these individuals. The current state of knowledge
      regarding Rett syndrome is reviewed and a framework is provided for medical and
      developmental interventions.

PMID- 8261728
TI  - Intergluteal dorsal dermal sinuses. The role of neonatal spinal sonography.

PMID- 8261729
TI  - Gustatory flushing syndrome. A pediatric case report and review of the
      literature.

PMID- 8261730
TI  - Evaluation of chloral hydrate for pediatric sedation.

PMID- 8261731
TI  - Increased serum phospholipase A2 activity in advanced chronic liver disease as an
      expression of the acute phase response.
AB  - Phospholipase A2 (PLA2) modifications were investigated in patients with acute
      and chronic liver diseases, PLA2 variations were related to indices of liver
      function as well as to parameters of the acute phase response. Serum PLA2
      activity modifications were fluorimetrically measured in 105 patients affected by
      acute and chronic liver diseases or extra-hepatic diseases. One-way ANOVA
      demonstrated a significant difference among groups (F = 4.53, P < 0.001);
      Bonferroni's test for pairwise comparisons showed that patients with
      hepatocellular carcinoma had higher mean values than subjects with benign extra
      hepatic diseases (P < 0.01) and mild chronic liver disease (P < 0.05). Multiple
      regression analysis, performed choosing PLA2 as the dependent variable and blood
      urea nitrogen, C-reactive protein, alkaline phosphatase and alpha 1-fetoprotein
      as predictor variables was significant (multiple R = 0.7056, multiple R2 =
      0.4978, F = 15.36, P = < 0.0001). The standardized regression coefficients found
      to be significant were those of C-reactive protein, blood urea nitrogen and alpha
      1-fetoprotein. In conclusion, in patients with chronic liver disease, serum PLA2
      activity increases parallel to disease severity and accompanies the expression of
      proteins of the acute phase response that, like PLA2 activity, increase in serum
      while liver synthesis declines.

PMID- 8261732
TI  - Parental HLA sharing, feto-maternal compatibility and neonatal birthweight in
      families with a history of recurrent spontaneous abortion.
AB  - The mean birthweight of babies eventually born to couples with a history of
      recurrent spontaneous abortion (RSA) is allegedly lower if the parents have a
      high degree of HLA antigen sharing (Reznikoff-Etievant et al., 1991), but this
      relationship has not been independently confirmed. We have re-investigated this
      question by analysing data from 36 families. In 22 instances, we were able to
      relate birthweight directly to feto-maternal HLA compatibility for the first time
      in such families. We were unable to confirm any appreciable influence of paternal
      or feto-maternal HLA sharing on birthweight or placental weight and conclude that
      RSA families do not differ markedly from normal families in this respect.

PMID- 8261733
TI  - TaqI digestion of PCR product increases the informativity of St14 VNTR for the
      diagnosis of hemophilia A.
AB  - Recently, a pair of PCR primers have been described that make it possible to
      amplify a highly polymorphic VNTR locus DX552 (St14). PCR products range in size
      from approximately 650 to 3000 bp. Ninety X chromosomes from unrelated Caucasian
      subjects were investigated. Digestion of the PCR products with TaqI revealed the
      presence of a polymorphic TaqI restriction site within the product 200 bp from
      the end. This restriction site is present on 60% and absent on 40% of all
      alleles, but the absence is confined solely to the alleles 1690 bp (39%) and 2100
      bp (1%). Thus, there is a strong allelic association between the most frequent
      1690 bp allele and the absence of the TaqI restriction site. Determination of
      this polymorphisms within the St14 VNTR region increases the expected
      heterozygosity at the DXS52 locus from 72% to 80%. This increases the fraction of
      hemophilia A families where this marker is informative for indirect prenatal
      diagnosis and carrier identification.

PMID- 8261734
TI  - Video image analysis in pathology.

PMID- 8261735
TI  - Glutathione transferase GST pi in breast tumors evaluated by three techniques.
AB  - The glutathione transferases are involved in intracellular detoxification
      reactions. One of these, GST pi, is elevated in some breast cancer cells,
      particularly cells selected for resistance to anticancer agents. We evaluated GST
      pi expression in 60 human breast tumors by three techniques,
      immunohistochemistry. Northern hybridization, and Western blot analysis. There
      was a significant positive correlation between the three methods, with complete
      concordance seen in 64% of the tumors. There was strong, inverse relationship
      between GST pi expression and steroid receptor status with all of the techniques
      utilized. In addition, there was a trend toward higher GST pi expression in
      poorly differentiated tumors, but no correlation was found between tumor GST pi
      content and DNA ploidy or %S-phase. GST pi expression was also detected in
      adjacent benign breast tissue as well as infiltrating lymphocytes; this
      expression may contribute to GST pi measurements using either Northern
      hybridization or Western blot analysis. These results suggest that
      immunohistochemistry is the method of choice for measuring GST pi in breast
      tumors.

PMID- 8261736
TI  - Luminoimmunometric assay of tissue polypeptide antigen (TPA) and cancer antigen
      125 (CA-125) in breast cancer patients.
AB  - Serum TPA and CA-125 were determined in 86 individuals (66 with breast cancer
      representing the different stages and grades of the disease and 20 normal healthy
      controls). TPA and CA-125 were estimated using the LIA reagents supplied by BYK
      Sangtec. TPA showed sensitivity rates of 31.8%, 42.4% and 51.5% while CA-125
      showed sensitivities of 16.3%, 18.6% and 25.6% at specificity levels of 100%, 95%
      and 90% respectively. Combined determination of the two markers resulted in some
      improvement in sensitivity. For follow-up of breast cancer patients after surgery
      both markers were of value and showed near-identical patterns.

PMID- 8261737
TI  - Immunohistochemical distribution of a breast cancer-associated glycoprotein.
AB  - The tissue distribution and specificity of a glycoprotein of M(r) 230,000 kDa
      which has previously been identified from breast carcinomas in culture and shown
      to be tumour-associated, has been assessed using a polyclonal antiserum. A wide
      range of tissues has been examined immunohistochemically. The tissue distribution
      of the glycoprotein show differences between normal, benign and malignant breast
      and other epithelial tissues, and are clearly specific for epithelial cells. This
      glycoprotein as detected by the polyclonal antiserum P5252-2, was either absent
      or showed a minimal presence in normal breast tissues. Evidence of the expression
      of the glycoprotein in hyperplastic breast was observed but was considerably less
      than that seen for carcinomas, for which 70% had greater than 50% of cells
      exhibiting reactivity with P5252-2. There was no relationship with grade or node
      status. Similar striking differences in glycoprotein expression between non
      neoplastic and neoplastic tissue were observed for stomach, large intestine,
      thyroid and to lesser extent ovary. The differences in the expression of this
      glycoprotein between normal and malignant tissues is of obvious clinical and
      pathological potential.

PMID- 8261738
TI  - The Colorado Medical Society and the threatened balkanization of the profession.

PMID- 8261739
TI  - What next? Legal system reform?

PMID- 8261740
TI  - The corporatization of health care.

PMID- 8261741
TI  - Colorado Medical Society guidelines for health system reform. Colorado Medical
      Society.

PMID- 8261742
TI  - Women physicians: are they taking over?

PMID- 8261743
TI  - Understanding health care integration--Part II.

PMID- 8261744
TI  - Entertainment is killing us.

PMID- 8261745
TI  - Times change.

PMID- 8261746
TI  - "Colorado Department of Health issues new report: Diabetes Prevalence and
      Morbidity in Colorado Residents, 1980-1991".

PMID- 8261747
TI  - Why clinical practice guidelines?

PMID- 8261748
TI  - DCCT: implications for diabetes care in the UK.

PMID- 8261749
TI  - Alpha-glucosidase inhibition as an adjunct to the treatment of type 1 diabetes.

PMID- 8261750
TI  - Microsatellite polymorphisms at the glucokinase locus: a population association
      study in Caucasian type 2 diabetic subjects.
AB  - Glucokinase has a central role in glucose metabolism in pancreatic beta cells and
      hepatocytes and is an important candidate gene for Type 2 diabetes. Mutations of
      the glucokinase gene have been reported in Caucasian pedigrees with maturity
      onset diabetes of the young and late-onset Type 2 diabetes. In population studies
      of American Blacks and Mauritian Creoles an association between alleles of a
      glucokinase polymorphism and Type 2 diabetes has been described. Two
      microsatellite polymorphisms (GCK 1 and GCK 2) flanking the glucokinase gene were
      investigated in Caucasian subjects. There was no significant linkage
      disequilibrium between the alleles of the two polymorphisms. The overall allelic
      frequencies for GCK 1 and the combined haplotyes did not significantly differ
      between 95 Type 2 diabetic and 76 normoglycaemic subjects. In an expanded cohort
      of 151 diabetic subjects the allelic frequencies at GCK 2 were also similar to
      controls. These results suggest that a single mutation of the glucokinase gene is
      not a common cause of Type 2 diabetes in English Caucasians.

PMID- 8261751
TI  - Urinary excretion and clearance of insulin in diabetic and normal children and
      adolescents.
AB  - Seventy-two diabetic (38 males) and 86 normal (41 males) children provided timed
      overnight urine collections. Fourteen of the diabetic and 33 of the normal
      children had concurrent overnight plasma insulin profiles. Urinary insulin
      clearance in the diabetic subjects was compared with excretion of albumin, growth
      hormone, retinol-binding protein, and N-acetyl-beta-D-glucosaminidase. In the
      normal subjects, urinary insulin excretion correlated with mean overnight plasma
      levels in the boys (r = 0.82, p < 0.001) but not in the girls (r = 0.32), and
      varied with puberty stage in the boys. Insulin clearance was greater in boys than
      girls during puberty, and fell in both sexes with advancing puberty. Insulin
      excretion was greater in diabetic than normal children in both sexes at all
      puberty stages. Insulin clearance was also greater in diabetic than normal
      subjects (1.05 +/- 0.1 ml min-1 1.73 m-2 vs 0.48 +/- 0.05 ml min-1 1.73 m-2, p <
      0.001). Insulin excretion as a percentage of the filtered load was also greater
      in diabetic than normal subjects (1.9 +/- 0.27% vs 0.85 +/- 0.09%, p < 0.01). In
      the diabetic children, there was a correlation between urinary insulin and growth
      hormone excretion (r = 0.52, p < 0.02), and retinol-binding protein in those (n =
      10) with higher retinol binding protein excretion (r = 0.76, p = 0.01). The value
      of urinary insulin excretion as a measure of free plasma insulin levels in normal
      and diabetic children may be limited by sex differences in renal insulin
      clearance, and by proximal renal tubular dysfunction in children with diabetes.

PMID- 8261752
TI  - Preservation of renal haemodynamic response to an oral protein load in non
      insulin-dependent diabetes mellitus.
AB  - Glomerular Filtration Rate (GFR) and Effective Renal Plasma Flow (ERPF) were
      determined, for 2 h prior to and 3 h following the ingestion of a 1.2 g kg-1 meat
      meal, in seven normotensive normoalbuminuric Type 2 diabetic patients exhibiting
      good glycaemic control (fasting plasma glucose (mean +/- SD): 7.2 +/- 2.0 mmol l
      1; glycosylated haemoglobin: 8.1 +/- 1.7%) and in nine normal subjects selected
      for similar basal GFR values. Baseline GFR and ERPF (corrected to 1.73 m2 surface
      area) were 83 +/- 10 and 410 +/- 76 ml min-1 for the Type 2 diabetic patients and
      86 +/- 11 and 405 +/- 113 ml min-1 for the normals. GFR increased by 38 +/- 8 and
      32 +/- 15% in the diabetic patients and normals, to 108 +/- 25 and 105 +/- 26 ml
      min-1 (p < 0.01 vs baseline). Peak ERPF was 501 +/- 127 and 476 +/- 119 ml min-1
      for the two respective groups (p < 0.01 vs baseline). Filtration fractions at
      peak GFR and EPRF values were unchanged from baseline for either groups.
      Fractional clearance of albumin for the Type 2 diabetic patients was unaltered by
      protein ingestion. Therefore, protein ingestion in Type 2 diabetes, as in
      normals, results in an acute elevation of GFR. Absolute and incremental changes
      in GFR were identical for the two groups. These data demonstrate a preserved
      capacity for renal vasodilatation in Type 2 diabetic patients despite their
      greater chronological age.

PMID- 8261753
TI  - Dermatoglyphics in type 1 diabetes mellitus.
AB  - Although fingerprints and handprints are widely used in criminology, it is only
      recently that this approach has been applied to the field of medical and genetic
      diagnoses. In order to investigate dermatoglyphics in Type 1 diabetes mellitus,
      quantitative characteristics of fingers and palms (ridge count and main line
      indices) as well as qualitative parameters such as digital and interdigital
      patterns, the position of the palmar axial triradii and main line courses were
      analysed in 88 male and 108 female Type 1 diabetic patients and compared with
      data from 100 male and 99 female normal controls. Type 1 diabetic patients show a
      lower third finger ridge count (p < 0.05) and a-b ridge count (p < 0.001) and
      higher transversality of the main lines as indicated by the main line index value
      (p < 0.001) or the ending of the main line A in a specific sector 5, 5', and 5"
      (p < 0.001) compared with controls. In addition, diabetic patients show higher
      frequency of palmar axial t' and t" triradii (p < 0.001) and a lower frequency of
      'true' patterns in the fourth interdigital and thenar area (p < 0.001) than
      controls. By multivariate analysis of quantitative and qualitative variables a
      predictive value of 78.6% and 77.3%, respectively, for male, and 81.4% and 82.2%,
      respectively, for female Type 1 diabetic patients was found. In conclusion,
      dermatoglyphics seem to be an interesting tool for genetic studies related to
      Type 1 diabetes.

PMID- 8261754
TI  - Necrobiosis lipoidica diabeticorum: association with background retinopathy,
      smoking, and proteinuria. A case controlled study.
AB  - In order to evaluate patients with necrobiosis lipoidica diabeticorum and to
      compare them with age, sex, and duration of diabetes matched controls, 15
      patients with necrobiosis were each matched with 5 control subjects with diabetes
      mellitus. Complications of diabetes, glycaemic control, and proteinuria were
      measured. Patients with necrobiosis (mean age 40, range 18-74 years) had a mean
      duration of diabetes of 14 (range 3-36) years; 8 patients were male, and 7 were
      female. For necrobiosis versus controls, background retinopathy (67% vs 27%, p =
      0.009), proteinuria (53% vs 17%, p = 0.006), and smoking (60% vs 20%, p = 0.003)
      were all more common with necrobiosis. There were no significant differences
      between patients with necrobiosis and control patients in the prevalence of
      vascular disease and neuropathy. Glycosylated haemoglobin concentrations were
      higher in patients with necrobiosis (p = 0.02). Blood pressure measurements were
      similar in both groups. We conclude that smoking, proteinuria, and retinopathy
      were more prevalent in diabetic patients with necrobiosis; the skin lesion may
      therefore share common aetiological factors which affect the microvascular
      circulation, leading to damage to basement membranes and vascular endothelial
      cells.

PMID- 8261755
TI  - Energy expenditure in lean and obese diabetic patients using the doubly labelled
      water method.
AB  - Obesity is a common problem among Type 2 diabetic patients. To investigate the
      role of energy expenditure in the maintenance of obesity in diabetic subjects,
      total energy output was measured during weight stability in 23 diabetic patients:
      8 lean, 5 overweight, and 10 obese. Free living total energy expenditure was
      measured over 14 days using doubly labelled water method, resting metabolic rate
      by indirect calorimetry, and urinary energy losses were assessed. Total energy
      output was higher in the obese (13.66 +/- SD 3.18 MJ 24 h-1) than normal weight
      patients (10.84 +/- 2.02 MJ 24 h-1; p < 0.05); 11.96 +/- 2.51 MJ 24 h-1 in the
      overweight. None of the lean but four of the obese had total energy output > 16
      MJ 24 h-1. Urinary energy losses accounted for only 0.6% of total energy output
      in lean, 2.8% in overweight, and 3.1% in obese. Resting metabolic rate was
      significantly higher in obese (7.47 +/- 1.69 MJ 24 h-1) compared to lean (5.87 +/
      1.07; p < 0.05) and resting metabolic rate correlated with lean body mass (r =
      0.8, p < 0.001). Thermogenesis plus physical activity was substantial and not
      lower in the obese (5.77 versus lean 4.97 MJ 24 h-1). The mean ratio of total
      energy expenditure to resting metabolic rate was in the moderate exercise
      category and similar in lean (1.87) and obese (1.80). Resting metabolic rate,
      total energy expenditure, and thermogenesis and physical activity were similar in
      all three groups when corrected for differences in lean body mass.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8261756
TI  - Absorption of radiolabelled soluble insulin in type 1 (insulin-dependent)
      diabetes: influence of subcutaneous blood flow and anthropometry.
AB  - The rate of absorption of soluble insulin, and its relationships with
      subcutaneous blood flow (SCBF) and patients' anthropometry, were investigated in
      12 male Type 1 (insulin-dependent) diabetic patients of less than 10 yr disease
      duration (age range: 23-29 yr; body mass index (BMI): 22.2-30.8 kg m-2).
      Simultaneous assessment of the absorption of 125I-labelled soluble insulin and
      SCBF (99mTechnetium clearance) were performed, on separate study days, for the
      anterior abdominal wall, anterior mid-thigh, and the upper arm injection sites.
      Absorption of 125I soluble insulin, including during the lag-phase, was
      determined by the two- and three-parameters biexponential models description of
      residual radioactivity levels at the injection site. Anthropometric measurements
      utilized were: BMJ, ultrasonic measurement of the subcutaneous adipose tissue
      layer, and caliper skinfold thickness at anterior abdominal wall, biceps,
      triceps, anterior mid-thigh and subscapular sites. Rate-constants for absorption
      of soluble insulin were positively correlated with SCBF (Spearman rank
      coefficient (rs) = 0.33-0.55; p < 0.01-0.001). An inverse relationship was
      observed between the duration of the lag-phase and SCBF (rs = -0.28 - -0.54; p <
      0.05-0.001). Patients' degree of adiposity was inversely correlated with the rate
      of soluble insulin absorption (rs = -0.24 - -0.28; p < 0.05) and SCBF (rs = -0.28
      - -0.43; p < 0.05-0.001). Consequently, faster absorption of soluble insulin,
      with shorter lag-phase duration, was noted for the abdominal and thigh sites for
      non-obese (BMI > 25 kg m-2) than obese patients (BMI < 27.5 kg m-2) (p < 0.05
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261757
TI  - Application of physicians' predictions of meal and exercise effects on blood
      glucose control to a computer simulation.
AB  - Our aim was to develop a computer simulator program that allows patients to
      practise insulin dose and dietary adjustment on a day of planned exercise, and
      shows the resulting blood glucose response in an average diabetic patient. The
      degree of blood glucose change predicted by the program was determined from
      changes predicted by five local specialists in seven hypothetical scenarios
      involving exercise +/- dietary or insulin dose adjustments. The program was then
      tested against 18 outside specialists' responses in 7 different scenarios. The
      program simulates the 24 h glycaemic response after 45 min mild or moderate
      exercise starting 2 h after meals, as well as changes to this response induced by
      alterations in dietary carbohydrate and/or insulin dose. Coefficients of
      variation of specialists' blood glucose predictions were greater for exercise
      (35% local, 31% outside specialists) than dietary change (7% local, 10% outside
      specialists; p = 0.002-0.04). The program's predicted change in blood glucose
      levels in the seven scenarios correlated well with the outside specialists'
      corresponding mean predictions (r = 0.97; p = 0.0001). We conclude that
      specialists are less consistent in predicting glycaemic change with exercise than
      with dietary alteration. Nevertheless it is possible to represent their
      predictions in a computerized simulator for diabetic patient education.

PMID- 8261758
TI  - Metabolic and clinical characteristics of south Asians and Europeans in Coventry.
AB  - A house to house survey in Foleshill, Coventry, compared risk factors for Type 2
      diabetes and ischaemic heart disease (IHD) among adult United Kingdom Europeans
      (n = 5508, 64% screened) and South Asians (n = 4395, 84% screened). Those with a
      high glucose and a randomized 10% of others had a glucose tolerance test while
      those with previously diagnosed diabetes (104 Europeans, 223 South Asians) were
      re-interviewed in more detail. By the age of 29 years, South Asians had higher 2
      h glucose 5.4 +/- 1.0 vs 4.84 +/- 1.2 mmol l-1, p < 0.005) and insulin (45.6 vs
      23.8 mU l-1, p < 0.001) concentrations and in males, a higher cholesterol
      concentration (5.1 +/- 0.9 vs 4.6 +/- 1.2 mmol l-1, p < 0.05). South Asians with
      known Type 2 diabetes had an earlier age at diagnosis (48 +/- 11 vs 57 +/- 14
      years, p < 0.001), a lower body mass index in the past (29.0 +/- 4.8 vs 32.1 +/-
      6.9 kg m-2, p < 0.001) and currently (27.1 +/- 3.7 vs 29.1 +/- 6.4 kg m-2, p <
      0.001), were more likely to present with acute symptoms, were less likely to
      attend the hospital clinic (14% vs 31%, p < 0.001), and were less likely to be
      treated with diet alone (14% vs 21%) or with insulin (9% vs 16%) than Europeans.
      Glycaemic control was similar in the two ethnic groups. These findings suggest an
      earlier onset of the disease processes involved in diabetes in South Asians.
      Important ethnic differences in patterns of care exist that make clinical
      comparisons difficult.

PMID- 8261759
TI  - The size of the pancreas in diabetes mellitus.
AB  - To determine whether there was an association between the size of the pancreas
      and the type of diabetes, ultrasonography of the pancreas was performed on 57
      diabetic patients: 14 with Type 1 (insulin-dependent) diabetes, 10 insulin
      treated and 33 tablet-treated patients with Type 2 (non-insulin-dependent)
      diabetes, and 19 non-diabetic subjects. The pancreas of patients with Type 1
      diabetes was markedly smaller (p < 0.0001) than the pancreas in non-diabetic
      subjects. The pancreas of patients with Type 2 diabetes was more moderate in
      size: larger (p < 0.001) than that of Type 1 diabetic patients but smaller (p <
      0.5) than the pancreas of the control group. Pancreatic size of patients with
      Type 2 diabetes was also related to basal insulin secretion with insulin
      deficient patients (low or undetectable C-peptide) having smaller (p < 0.05)
      pancreases than those with normal insulin secretion. There was no difference in
      the size of the pancreas in the different treatment groups of Type 2 diabetic
      patients. Pancreatic size did not correlate with age, body mass index or the
      duration of diabetes. We conclude that the pancreas is a smaller organ in
      patients with diabetes mellitus and that the decrement in size is maximal in
      insulin-dependent/insulin-deficient subjects. Ultrasonography, therefore, can
      potentially serve to discriminate between the different types of diabetes.

PMID- 8261760
TI  - Insulin treatment, time-zones and air travel: a survey of current advice from
      British diabetic clinics.
AB  - To investigate current advice given to insulin-treated diabetic patients
      undertaking international flights crossing time-zones, we have conducted a survey
      of UK physicians running diabetic clinics. Consultants were asked to give the
      general advice they would give to travellers on twice-daily short- and
      intermediate-acting insulins in four different flight situations: westward London
      to New York (morning and evening departures) and eastward Manchester to Singapore
      (morning and evening departures). Response rate was poor (37%). Six percent of
      replies were unhelpful (e.g. 'ring the BDA', 'carry on as usual'), and 14% liable
      to cause hypoglycaemia. Thirteen percent advocated change to a 'basal-bolus'
      system of insulin administration. The rest used variants of additional insulin
      for westward flights and reduced flights eastward. There was great variation in
      advice, and many regimens were excessively complicated. We recommend simple
      individualized advice, without attempts at over-zealous glycaemic control during
      travel. Local arrival and departure times may fit in easily with insulin and
      meals at standard times before and after flying, and little or no dosage
      alteration may be needed.

PMID- 8261761
TI  - Living with diabetes: relationship to gender, duration and complications. A
      survey in northern Sweden.
AB  - A questionnaire was sent to 561 insulin-treated diabetic patients aged 20-50
      years living in the province of Vasterbotten in Northern Sweden to assess their
      experience of living with diabetes. The response rate was 87% (n = 488).
      Differences in the experience of living with diabetes related to gender, age,
      duration of diabetes, and chronic diabetic complications were reported. Men
      seemed to underestimate problems related to diabetes more than women. They
      worried less about long-term complications and hypoglycaemia, but were more
      troubled by the limitation of personal freedom caused by their diabetes. In spite
      of their worries, women more often than men found positive aspects in having
      diabetes. Younger patients also had a more positive attitude towards their
      disease, even though they more often thought that diabetes had negatively
      affected their relationships with friends. Patients with a shorter diabetes
      duration were more concerned about the management of their diabetes than were
      patients with a long duration. The fear of chronic complications increased with
      diabetes duration. Chronic complications most affected patients' views of
      diabetes, their self-perception, and social life. Patients with childhood onset
      of diabetes knew less about the implications of the disease, and this reduced the
      intensity of their psychological response to the diagnosis. In conclusion, social
      and medical factors affected how diabetic patients perceived their disease. These
      findings suggest that the outcome of diabetes health care might improve if it was
      more individually adapted to each patient's personal experience of the disease
      and the psychological needs related to it.

PMID- 8261762
TI  - The Gulf War and diabetes mellitus.
AB  - The Gulf war was a traumatic and stressful event for the inhabitants of Tel-Aviv
      and vicinity. The entire population changed its way-of-life. In order to evaluate
      the influence of the war stress on glucose control, we reviewed the charts of all
      diabetic patients attending the outpatient clinics at the Tel-Aviv Medical
      Centre, whose weight and glycated haemoglobin was determined between 15.1.91 and
      2.5.91 (the war period), with comparative measurements within 4 1/2 months both
      before and after these dates. Sixty-six patients with non-insulin dependent
      diabetes mellitus (NIDDM) and 16 with insulin-dependent diabetes mellitus (IDDM)
      were examined. During the war, their glycated haemoglobin increased by 10.1 to
      10.9% and from 9.6 to 10.2%, respectively. Weight increased from 76.1 to 77.5 kg
      in the NIDDM and from 63.2 to 64.7 kg in the IDDM patients. Both measurements
      returned to baseline after the war. No correlation was found between the changes
      in glycated haemoglobin and weight.

PMID- 8261763
TI  - Population screening for diabetes mellitus. Professional Advisory Committee of
      the British Diabetic Association.
AB  - The role and value of screening for diabetes mellitus is still unclear. If
      asymptomatic subjects are to be screened, then a fasting plasma glucose > 6.6
      mmol l-1 or a venous plasma glucose 2 h after a 75 g oral glucose load > 8.0 mmol
      l-1 or the presence of any glucose in a urine sample passed 2 h after a main meal
      should be regarded as a positive result. A fasting plasma glucose in the range
      5.5-6.6 mmol l-1 is an equivocal result which should lead to retesting in 6-12
      months if there is any risk factor for diabetes (obesity, family history of
      diabetes, Asian/African racial origin). Other screening tests or combinations of
      tests are not recommended. Screening should be restricted to subjects between 40
      and 75 years and should be undertaken only every 5 years (3 years if a risk
      factor for diabetes is present), ideally in parallel with other health screening
      test; subjects with a positive result should have further investigations as
      necessary to reach a diagnosis in line with WHO criteria.

PMID- 8261764
TI  - Persisting mortality in diabetic ketoacidosis.

PMID- 8261765
TI  - Phimosis and treatment for erectile failure.

PMID- 8261766
TI  - Lyme disease.

PMID- 8261767
TI  - Sexually transmitted diseases.

PMID- 8261768
TI  - Prevention of occupational exposure to human immunodeficiency virus 1.

PMID- 8261769
TI  - Epidemiology of nosocomial Clostridium difficile infection.
AB  - C. difficile is a frequent cause of nosocomial diarrhea and is associated with
      substantial morbidity. C. difficile carriage may arise either from overgrowth of
      endogenous organisms or from exogenous acquisition. Within hospitals,
      asymptomatically colonized patients typically outnumber symptomatic patients by a
      ratio of approximately 3:1. Patient-to-patient transmission of C. difficile has
      been well documented in studies of nosocomial outbreaks, utilizing typing methods
      to supplement epidemiologic investigations. The mechanisms and frequency of
      transmission probably vary between institutions, but contamination of
      environmental surfaces and personnel hand carriage both appear to be important.
      Nosocomial C. difficile infection can be remarkably difficult to control,
      particularly after it becomes endemic in an institution. Policies targeting both
      environmental contamination and personnel hand-washing/glove use practices may be
      most successful. Prophylaxis of C. difficile diarrhea in high-risk patients on
      antibiotics may also have merit if an effective and safe biologic agent can be
      identified. Asymptomatically colonized patients should not be treated because
      they are at low risk for the development of diarrhea and because further
      antibiotic treatment may prolong the carrier state.

PMID- 8261770
TI  - Lyme disease.

PMID- 8261771
TI  - Neural networks and nonlinear regression modelling and control of depth of
      anaesthesia for spontaneously breathing and ventilated patients.
AB  - Various attempts have been made to control the depth of anaesthesia by observing
      different variables. In some studies, depth of anaesthesia has been correlated
      with inferential parameters and the control has been made through these inferred
      parameters. No single system has been reported which provides a fully developed
      architecture to control the depth of anaesthesia. This study is concerned with
      the development of controllers and patient models via Artificial Neural Networks
      and regression analysis. Two types of data sets were used for the training and
      development of models and controllers. The first set was for spontaneously
      breathing and the second set for ventilated patients. All of the controllers and
      patient models gave satisfactory results when tested individually. Later these
      two sets of controllers and patient models were studied in closed-loop modes. The
      robustness to the sensitivity of the regression patient model was also
      investigated. Various tests were performed with these closed-loop situations.
      Results and performance of these tests are discussed in the paper.

PMID- 8261772
TI  - Bioequivalence revisited: non-parametric analysis of two-period cross-over
      studies.
AB  - Hauschke et al.'s non-parametric bioequivalence procedure for treatment effects
      and some aspects of computer implementation, among them Meineke and De Hey's
      algorithm and a recursive algorithm, are explored. For studies with up to sixty
      subjects, a table of indices of the ranked intersubject-intergroup mean ratios or
      differences is given, to establish non-parametric 90% confidence intervals. It is
      shown that non-parametric analysis is not limited to treatment effects: it can
      also be applied to period and sequence effects. This extended procedure can be
      seen as the non-parametric analogue of analysis of variance on two-period cross
      over studies. A FORTRAN program (BIOEQNEW) incorporating Meineke and De Mey's
      algorithm is presented. This program provides non-parametric point estimates for
      treatment and period effects, 90% and 95% confidence intervals for test-versus
      reference treatments, the 95% confidence interval for periods and a test on
      sequence effects, so that it can also be used for other than bioequivalence
      studies. BIOEQNEW can handle ratios ('multiplicative model') as well as
      differences ('additive model'). It optionally provides the complete non
      parametric posterior probability distribution for treatment ratios or
      differences, so that Schuirmann's 'two one-sided tests procedure' can also be
      performed in a non-parametric way.

PMID- 8261773
TI  - Meta-analysis of clinical trials based on censored end-points: simplified theory
      and implementation of the statistical algorithms on a microcomputer.
AB  - Meta-analysis is increasingly being used in clinical research. While the meta
      analytical algorithms for pooling the results of studies using non-censored end
      points are now sufficiently standardized, the management of trials based on
      censored end-points is still controversial, and specific algorithms of meta
      analysis are still needed (for example, censored end-points are commonly used in
      survival studies of cancer patients). In the present article we review the
      various algorithms that have thus far been utilized to perform a meta-analysis
      based on censored end-points, and we propose a new and original approach that
      combines two of the existing algorithms. Our approach is designed to formulate
      any meta-analysis of survival studies in terms of the calculation of an odds
      ratio. The meta-analytical odds ratio proposed here is called the 'log-rank' odds
      ratio of meta-analysis. A microcomputer program is described that implements the
      various methods of meta-analysis that can handle clinical trials based on
      censored end-points. Some examples are presented to illustrate the use of the
      program.

PMID- 8261774
TI  - Management of cytogenetic data in multi-center leukemia trials.
AB  - This paper provides methods for storing and retrieving cytogenetics data, which
      must reside jointly in a reference laboratory and in a data co-ordinating center.
      The major piece of data is the character string that uses the International
      System for Human Cytogenetic Nomenclature. Simple and complex data retrieval,
      using Statistical Analysis System (SAS) functions INDEX and SUBSTR, are
      illustrated. Use of the methods of this paper can save considerable costs in
      setting up cytogenetic data systems compared with other proposed systems which
      have come to the authors' attention.

PMID- 8261775
TI  - MULCOX2: a general computer program for the Cox regression analysis of
      multivariate failure time data.
AB  - Multivariate failure time data is commonly encountered in biomedicine, because
      each study subject may experience multiple events or because there exists
      clustering of subjects such that failure times within the same cluster are
      correlated. MULCOX2 implements a general statistical methodology for analyzing
      such data. This approach formulates the marginal distributions of multivariate
      failure times by Cox proportional hazards models without specifying the nature of
      dependence among related failure times. The baseline hazard functions for the
      marginal models may be identical or different. A variety of statistical inference
      can be made regarding the effects of (possibly time-dependent) covariates on the
      failure rates. Although designed primarily for the marginal approach, MULCOX2 is
      general enough to implement several alternative methods. The program runs on any
      computer with a FORTRAN compiler. The running time is minimal. Two illustrative
      examples are provided.

PMID- 8261776
TI  - Metabolic compatibility of abattoir and human corneas: an ex vivo 31P nuclear
      magnetic resonance spectroscopic study of intact tissues.
AB  - This study establishes the metabolic similarities and differences of intact
      abattoir corneas and the human cornea ex vivo, using 31P nuclear magnetic
      resonance spectroscopy. Phosphorylated sugars (SP), inorganic orthophosphate
      (Pi), phosphodiesters, ATP, ADP, and the nucleoside diphosphosugars and
      dinucleotides (NS&DN) were quantitated. The intracorneal pH also was determined.
      In addition, metabolic indices ATP/Pi, ATP/ADP, ATP/(ADP + Pi), SP/Pi, the
      phosphorylation potential, and the 31P energy modulus were calculated.
      Significant differences were observed between the abattoir and human corneas in
      phosphorylated sugars, NS&DN, and intracorneal pH, as well as in the indices
      ATP/ADP and SP/Pi. The overall energy status as measured by the 31P energy
      modulus was significantly higher in the bovine cornea when compared to the
      porcine and human corneas, suggestive of a very high energy reserve in the bovine
      cornea.

PMID- 8261777
TI  - Image processing of electron micrographs for light scattering calculations.
AB  - Theoretical light scattering calculations, when applied to models based on
      structures seen in electron micrographs of corneal stroma, require knowledge of
      the constituent fibril positions and radii. Obtaining this information manually
      is a difficult and time-consuming task. In order to facilitate this problem, we
      present a simple and flexible computer algorithm that allows the process to be
      automated using a Macintosh computer. The accuracy of the results is checked by
      comparing light scattering calculations using fibril positions and radii found
      manually with those found by the computer. The results show that the computer
      algorithm is a viable and accurate means of obtaining the needed data.

PMID- 8261778
TI  - Immunological analysis and treatment of Mooren's ulcer with cyclosporin A applied
      topically.
AB  - Mooren's ulcer is a chronic, painful rodent nonpurulent corneal ulcer. In order
      to discern the possible role that immunological processes (antibody and cell
      mediated) play in the development of a Mooren's ulcer, we evaluated sera from
      patients (n = 16) for the presence of circulating antibodies against normal
      rabbit and human corneal epithelium using an indirect immunofluorescent technique
      (IFT) and determined the T-lymphocyte subsets (CD4, CD8, CD11) in the peripheral
      blood. This condition was treated with an immunophilin, cyclosporin A (CsA) (0.5%
      solution), applied topically. Antibodies against rabbit corneal epithelium were
      detected in 12 of 16 patients (75%), while only six of 16 (37.5%) patients had
      antibodies against human corneal epithelium. The percentage of CD8 (suppressor T
      cells) T lymphocytes was significantly lower in patients with Mooren's ulcer than
      in the controls (p < 0.01). Mooren's ulcer was effectively treated with 0.5% CsA
      in 11 of 18 (61.1%) affected eyes (n = 14 patients), as determined by long-term
      (24-31 months) follow-up. We noted particularly that regulatory imbalance existed
      in the immune systems of the patients. We also think that the limbus and
      conjunctival lymphoid tissue adjacent to the limbus might play an important role
      in the pathogenesis of the disease. The detection of serum antibodies against
      corneal epithelium and determination of T-lymphocyte subsets in the peripheral
      blood may provide a referential basis for the clinical diagnosis of Mooren's
      ulcer. Effective treatment with 0.5% topical CsA is primarily through the
      depression of ocular immunoreactions, although systemic action is not completely
      ruled out.

PMID- 8261779
TI  - Suture abscesses after penetrating keratoplasty.
AB  - Eighteen suture abscesses that developed after penetrating keratoplasty in 15
      patients were reviewed. The time from keratoplasty to the diagnosis of an abscess
      ranged from 1 to 53 months with a mean of 21.5 months. In 13 of the 18 cases, the
      patient was taking topical steroids at the time of diagnosis. All were culture
      proven bacterial ulcers, except for one case that had a positive Gram's stain,
      but no growth on culture. The organisms cultured were Staphylococcus epidemidis
      (six eyes), Streptococcus pneumoniae (five eyes), Sta. aureus (four eyes), Str.
      viridans (two eyes), Klebsiella oxytoca (one eye), Serratia marcescens (one eye),
      Moraxella sp (one eye), and Escherichia coli (one eye). The offending suture was
      removed in all cases, and the eyes were treated with topical fortified
      antibiotics (cefazolin and tobramycin). After treatment, 67% (12 of 18 eyes) had
      clear grafts, 17% (three of 18 eyes) were scarred, and 16% (three of 19 eyes) had
      failed grafts. Intensive topical steroid therapy was used when a subsequent graft
      rejection developed. Retained sutures following corneal transplants can result in
      sight-threatening infections and should be considered for removal as soon as the
      wound is well healed.

PMID- 8261780
TI  - Changes in corneal autofluorescence and corneal epithelial barrier function with
      aging.
AB  - Corneal epithelial permeability studies using fluorophotometers were performed on
      90 eyes of 51 normal subjects. After recording the autofluorescence of the cornea
      (AFC) and of the lens (AFL), we applied 20 microliters of 2% sodium fluorescein
      to the conjunctival sac. The corneal fluorescence 45 min later (F45), which
      paralleled the corneal epithelial permeability to fluorescein, was measured by
      fluorophotometer and analyzed. All parameters of the two eyes of each subject
      correlated well with each other. There was positive correlation between AFL and
      patient age and between AFC and patient age (r = 0.78, p < 0.001, and r = 0.74, p
      < 0.001, respectively). The F45 increased exponentially with advancing age (r =
      0.67, p < 0.001). The strong correlation between AFC and AFL in each eye (r =
      0.79, p < 0.001) indicated corresponding aging processes in both the cornea and
      the lens. The increase in epithelial permeability with age possibly represents a
      subclinical breakdown of barrier function, rendering the corneas more vulnerable
      to insults.

PMID- 8261781
TI  - Surface quality of excimer laser corneal ablation with different frequencies.
AB  - To test the effects of different frequencies of a 193-nm excimer laser on the
      surface smoothness of the ablated materials and the damage to the adjacent
      structure, four different frequencies (5, 10, 15, and 20 Hz) of a 193-nm excimer
      laser were used to perform ablations on 20 rabbit corneas and four
      polymethylmethacrylate blocks at a fluence of 160 mJ/cm2. Each frequency was
      tested five times on five corneas. The ablated materials were processed and
      examined with scanning electron microscopy (SEM) and light and transmission
      electron microscopy (TEM) and a Zygo interference microscope, which
      quantitatively evaluates the surface smoothness. The results from the Zygo
      microscope show that there is no statistically significant difference in surface
      smoothness between any two different frequencies. The SEM reveals similar
      regularity and uniformity on the ablated surfaces, with no relationship between
      the laser frequencies and the amount of surface deposits. The TEM demonstrates no
      correlation between the various frequencies and the thickness of the superficial
      pseudomembrane and the amount of collateral damage in the adjacent stroma. It
      appears that the higher frequencies are comparable to the lower one (5 Hz) as to
      ablation quality, with the benefit of curtailing surgical time and decreasing the
      chances of eye movement.

PMID- 8261782
TI  - Effect of topical cyclosporin A on conjunctival T cells in patients with
      secondary Sjogren's syndrome.
AB  - The effect of topical cyclosporin A on conjunctival T cells was studied in nine
      patients with secondary Sjogren's disease. Patients had conjunctival biopsies
      performed before and after a 6-week course of topical cyclosporin. Epithelium and
      substantia propria in the Sjogren's patients before treatment showed
      significantly more CD4+ cells than specimens taken from nine age- and sex-matched
      controls. Following treatment with topical cyclosporin, there was a significant
      reduction in the number of CD4+ cells in both the conjunctival epithelium and
      substantia propria. Despite the fact that the treatment resulted in
      immunopathological improvement, the clinical benefit was not as favorable. Our
      results suggest that topical cyclosporin may have a local immunosuppressive
      effect on the conjunctiva in patients with Sjogren's disease.

PMID- 8261783
TI  - The qualitative evaluation of the pharmacokinetics of subconjunctivally injected
      antifungal agents in rabbits.
AB  - Dutch-belted rabbits with corneal epithelium either intact or debrided were
      injected subconjunctivally with 300 microliters of one of six antifungal agents:
      10 mg/ml miconazole, 5 mg/ml fluconazole, 5 mg/ml ketoconazole, 2.5 mg/ml
      itraconazole, and 5 mg/ml amphotericin B. At intervals of 10 min to 96 h after
      injection, animals were killed and corneas removed at the limbus. Three vertical
      strips from the right cornea and four contiguous 3-mm disks trephined from the
      central vertical axis of the left cornea were placed on agar plates seeded with
      an appropriate indicator organism. After 24 h of incubation, the zones of
      inhibition were measured. For itraconazole, miconazole, fluconazole,
      saperconazole, and ketoconazole, central corneal levels peaked by 2 h in normal
      and debrided corneas. Little or no drug was detectable after 4-8 h, except for
      itraconazole, which persisted in the cornea for at least 24 h in both normal and
      debrided corneas. Peak levels of amphotericin B in the central cornea were
      achieved after 2 h in rabbits with debrided corneas, with no drug activity
      measured after 8 h. There were no detectable levels of drug found in the central
      corneas of rabbits with intact corneal epithelium. On the basis of this pilot
      study, the method offers a rapid approach to the screening of antifungal agents
      for possible use by subconjunctival injection.

PMID- 8261784
TI  - Topical ciprofloxacin versus topical fortified antibiotics in rabbit models of
      Staphylococcus and Pseudomonas keratitis.
AB  - We tested the antibacterial activity of ophthalmic 0.3% ciprofloxacin against
      that of 5.0% cefazolin and 1.36% tobramycin in two experimental models of
      keratitis, using a methicillin-sensitive strain of Staphylococcus aureus and an
      aminoglycoside-sensitive strain of Pseudomonas aeruginosa, respectively. Both
      corneas of New Zealand white rabbits were intrastromally injected with either S.
      aureus or P. aeruginosa. Twenty-four hours later, each eye was topically treated
      hourly for 24 hours. In the S. aureus model, the control group received Tears
      Naturale Free (Alcon Laboratories, Inc., Fort Worth, TX), the ciprofloxacin group
      received 0.3%, ciprofloxacin and the cefazolin group received 5.0% cefazolin. In
      the P. aeruginosa model, the control group received Tears Naturale Free, the
      ciprofloxacin group received 0.3% ciprofloxacin, and the tobramycin group
      received 1.36% tobramycin. One hour after the last eyedrops were administered,
      the rabbits were killed, and their corneas were processed for quantification of
      bacteria. For the S. aureus model, the mean (+/- SEM) colony forming units (CFU)
      of the control, 7.1 x 10(6) (+/- 4.0 x 10(6)); ciprofloxacin, 6.4 x 10(2) (+/-
      1.6 x 10(2)); and cefazolin, 1.3 x 10(3) (+/- 1.8 x 10(2)) groups were different
      (F = 17.5; p = 0.001). The ciprofloxacin and cefazolin groups were not different
      from each other (p = 0.034). The mean (+/- SEM) CFU for the control group in the
      P. aeruginosa model was 2.8 x 10(8) (+/- 1.7 x 10(7)). All corneas in the
      ciprofloxacin and tobramycin groups were sterile.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8261785
TI  - Effects of polymorphonuclear neutrophils on protein synthesis by alkali-injured
      rabbit corneas. A preliminary study.
AB  - Invasion of polymorphonuclear neutrophils (PMN) into injured cornea is one of the
      early events in corneal wound-healing. In the present studies, we examine the
      mutual effects on protein synthesis by PMN and injured and normal corneas when
      they are cocultured. PMN were labeled with [35S]methionine in the presence or
      absence of normal or alkali-injured rabbit corneas for 1-5 h. The acid-insoluble
      35S-labeled proteins in medium, cells, and tissues were measured. Our data
      indicate that alkali-injured rabbit corneas induce higher rates of incorporation
      of [35S]methionine and secretion of 35S-labeled newly synthesized proteins by
      PMN. The newly synthesized 35S-labeled proteins were then analyzed by two
      dimensional PAGE. The results indicate that alkali-injured and normal rabbit
      corneas enhance the synthesis and secretion of a 18-kD protein by PMN. In
      contrast, alkali injury greatly reduced the secretion of a group of proteins
      having molecular weights of approximately 30 kD by rabbit corneas. The alkali
      injured corneas synthesize a new 200-kD protein (AC-200) in tissues and increase
      the secretion of a 120-kD protein (AC-120) into the culture medium. Furthermore,
      PMN slightly inhibits the incorporation of [35S]methionine and alter the
      synthesis of several 35S-labeled proteins by normal and injured corneas. For
      example, incubation with PMN abolishes the synthesis of the AC-200 protein, but
      enhances the secretion of the AC-120 protein by the alkali-injured corneas.
      However, the function and nature of these proteins remain largely unknown.
      Further studies are needed to elucidate the biological roles of these
      polypeptides during corneal wound healing.

PMID- 8261786
TI  - Fibrous histiocytoid leprosy of the cornea.
AB  - We describe a 50-year-old man with a 10-year history of gradually enlarging
      limbal tumors and conjunctival injection. An excised limbal mass presented a
      diagnostic challenge histopathologically and was initially believed to be a
      fibrous histiocytoma. Special stains, however, revealed acid-fast organisms in
      the fibrous histiocytes, and the diagnosis was changed to corneal leproma. This
      case confirms the existence of fibrous histiocytoma-like lesions in leprosy,
      which in this form can be termed fibrous histiocytoid leprosy. Furthermore, it
      suggests the need for special stains to rule out infectious cause in lesions
      believed to be atypical fibrous histiocytomas.

PMID- 8261787
TI  - Massive precorneal extension of squamous cell carcinoma of the conjunctiva.
AB  - A 73-year-old man had only light perception vision from a slowly enlarging fleshy
      papillomatous mass covering the entire cornea. The lesion was excised completely,
      leaving a clear corneal bed and 20/25 vision. Histopathologically, the lesion was
      found to be squamous cell carcinoma in situ with early microinvasion of the
      basement membrane. Viral studies for human papilloma virus were negative. This
      case represents a massive superficial involvement of the cornea by squamous cell
      carcinoma and shows the resistance of Bowman's membrane to tumor penetration.

PMID- 8261788
TI  - Effect of delle in Vogt Limbal girdle.

PMID- 8261789
TI  - DNA damage and repair in rabbit lens epithelial cells following UVA radiation.
AB  - Since ultraviolet light may be a contributing factor to cataractogenesis, we
      investigated the response of the lens epithelium, a potential target for UV
      insult, to UVA radiation. Cell survival and the induction and repair of DNA
      single-strand breaks (SSBs) were measured in cultured rabbit lens epithelial
      cells following UVA exposure. The light was passed through a filter which
      eliminated wavelengths below 335 nm in order to ensure that the cells were
      exposed only to UVA. In order to study the effect of various fluences of UVA on
      cell survival, 2 x 10(6) cells suspended in Tyrode's buffer were exposed to UVA.
      During all irradiations the cells were maintained at 0.5 degrees C in order to
      minimize DNA repair. Following UVA treatment, 200 cells were cultured in minimal
      essential medium containing 10% rabbit serum, and a colony forming assay was used
      to quantify cell survival. UVA induced cell death in a dose-dependent manner. In
      additional experiments, confluent epithelial cells on glass slides immersed in
      Tyrode's buffer were irradiated and SSBs were quantified using the alkaline
      elution technique. A 30 min exposure to UVA (180 KJ/m2) induced measurable SSBs.
      An increase in UVA fluence brought about an increase in the number of DNA SSBs.
      Rejoining of SSBs was measured after the cells were irradiated in Tyrode's for 2
      hrs and allowed to repair in the dark for 4 hrs at 36 degrees C in MEM containing
      10% serum. Eighty percent of the DNA SSBs were repaired within 4 hrs as
      determined by analysis of the alkaline elution profile. The repair kinetics were
      biphasic with an initial fast and subsequently slower component. The results
      indicate that UVA can induce SSBs in lens epithelial cells, that the cells can
      repair most UVA-induced SSBs, and that UVA treatment can be toxic to the
      epithelium.

PMID- 8261790
TI  - Dexamethasone induced ultrastructural changes in cultured human trabecular
      meshwork cells.
AB  - Glucocorticoid-induced ocular hypertension has been demonstrated in both animals
      and humans. It is possible that glucocorticoid-induced changes in trabecular
      meshwork (TM) cells are responsible for this hypertension. In order to elaborate
      further the effect of glucocorticoids on the trabecular meshwork, the
      ultrastructural consequences of dexamethasone (DEX) treatment were examined in
      three different human TM cell lines. Confluent TM cells were treated with 0.1
      microM of DEX for 14 days, and then processed for light, epifluorescent
      microscopy or transmission electron microscopy (TEM). The effect of DEX treatment
      on TM cell and nuclear size was quantified using computer assisted morphometrics.
      Morphometric analysis showed a significant increase in both TM cell and nuclear
      size after 14 days of DEX treatment. Epifluorescent microscopy of rhodamine
      phalloidin stained, control TM cells showed the normal arrangement of stress
      fibers. In contrast, DEX-treated TM cells showed unusual geodesic dome-like cross
      linked actin networks. Control TM cells had the normal complement and arrangement
      of organelles as well as electron dense inclusions and large vacuoles. DEX
      treated TM cells showed stacked arrangements of smooth and rough endoplasmic
      reticulum, proliferation of the Golgi apparatus, pleomorphic nuclei and increased
      amounts of extracellular matrix material. The DEX-induced alterations observed in
      the present study may be an indication of the processes that are occurring in the
      in vivo disease process.

PMID- 8261791
TI  - Sex-dependent parameters related to electrolyte, water and glycoprotein secretion
      in rabbit lacrimal glands.
AB  - The lacrimal glands of males and females of various species differ with respect
      to several morphological, biochemical and functional characteristics. The purpose
      of this study was to determine the effect of sexual maturation on Na+,K(+)
      ATPase, muscarinic cholinergic receptors and beta-adrenergic receptors, which are
      closely related to the secretion of electrolytes and fluid by the gland, and on
      other membrane-associated enzymes, specifically galactosyltransferase and
      alkaline and acid phosphatase. Soluble and total membrane fractions were obtained
      from lacrimal glands of prepubertal (1.0 kg), pubertal (2 kg), and mature (4 kg)
      of New Zealand white rabbits of both sexes. Prepubertal and pubertal rabbits
      exhibited no sex differences in the total amount of lacrimal gland protein or in
      any of the enzymes or receptors, with the exception of galactosyltransferase and
      alkaline phosphatase. Galactosyltransferase had higher total and specific
      activities in prepubertal and pubertal males, and alkaline phosphatase had higher
      specific activity in prepubertal males. As animals matured, total protein and
      activities of the enzymes increased, and several quantitative differences between
      males and females became apparent. Samples from mature females contained
      significantly less DNA and membrane and total protein. Specific activities of
      Na+,K(+)-ATPase, cholinergic receptors, galactosyltransferase, and acid and
      alkaline phosphatase were 40% to 80% greater (p < 0.05) in mature females. Total
      and specific activity for beta-adrenergic receptors, on the other hand, were
      higher in the male rabbits. These findings suggest that sex hormones play a role
      in regulating the levels of expression of a number of enzymes and receptors,
      including several which are clearly involved in lacrimal secretory functions.

PMID- 8261792
TI  - Circadian rhythm of neuropeptide Y-like immunoreactivity in the iris-ciliary body
      of the rat.
AB  - Neuropeptide Y (NPY)-like immunoreactivity (LI) in the iris-ciliary body of rats
      kept under constant darkness (DD) and in 12 h light-12 h dark cycle (LD) was
      determined by enzyme immunoassay. NPY-LI contents in the iris-ciliary body were
      found to oscillate in circadian fashion under DD and LD conditions, with a peak
      at about circadian time 12 (CT 12) and a trough at around CT 0. Unilateral
      superior cervical ganglionectomy caused a significant decrease in NPY-LI levels
      in the sympathectomized eye compare to the contralateral intact eye, independent
      of lighting phase. These results suggest the presence of an endogenous circadian
      rhythm in NPY-LI content in the rat iris-ciliary body, and the possible
      involvement of a sympathetic input from the superior cervical ganglion.

PMID- 8261793
TI  - Optical mapping of inner retinal tissue PO2.
AB  - A high resolution optical mapping procedure was developed to visualize oxygen
      concentration levels topographically within the tissue of the inner retina in
      vivo. The novel optical mapping procedure has the potential for describing oxygen
      metabolism in retinal and other body tissues and elucidating the coupling of
      metabolism to function. The method is based upon the fluorescence quenching by
      molecular oxygen of a lipid soluble probe substance which accumulates within the
      lipid bilayers of tissue cells. The optical mapping system can provide more than
      300,000 values of tissue PO2 in space with millisecond time resolution. Optical
      maps of inner retinal tissue PO2 were imaged under conditions of normoxia,
      hyperoxia, and for a retina which received restricted panretinal
      photocoagulation. Moreover, the effects of transient increases in intraocular
      pressure were also investigated. An O2 consumption rate of 5.48 +/- 0.50 (SEM) x
      10(-3) ml O2/ml tissue/min for the light-adapted rat inner retina was estimated
      from the application of a Krogh cylinder diffusion model to tissue PO2 gradients
      measured in the capillary-free zone around arterioles. Similarly, arterioles
      oxygenated a surrounding cylinder of tissue with a mean radius of 144.73 +/- 5.52
      (SEM) microns. Histograms of PO2 values within inner retinal tissue (mean PO2 =
      25.03 mm Hg, median = 24.58 mm Hg) showed remarkable correspondence to those
      determined invasively in brain by others, using O2 microcathodes, possibly
      suggesting a similarity in the underlying capillary architectures of the two
      neural tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261794
TI  - Splenectomy abrogates the induction of oral tolerance in experimental autoimmune
      uveoretinitis.
AB  - Oral administration of uveitogenic antigens inhibits the development of
      experimental autoimmune uveoretinitis (EAU) and the cellular immune response
      initiated by these antigens. The mechanism of oral tolerance is not completely
      clear, but accumulating data indicate that suppressor cells are actively involved
      in this process. The spleen is known to harbor suppressor cells and their
      precursors and the present study was aimed at testing the role of this organ in
      the induction of oral tolerance by S-antigen (S-AG). We report here that: (a)
      splenectomy abrogated the induction of oral tolerance; unlike in sham operated
      controls, feeding with S-Ag did not inhibit the development of EAU in
      splenectomized rats; (b) splenectomized rats responded with higher cellular
      immune responses than did sham operated controls, but feeding with S-Ag inhibited
      these responses in both groups of animals; (c) splenectomy also abrogated the
      adoptive transfer of tolerance: EAU induction was inhibited in sham operated
      recipients of splenocytes from S-Ag fed donors but not in the splenectomized
      recipients. The data thus indicate that the spleen plays an important role in the
      induction of oral tolerance, perhaps by acting as the site for induction and/or
      amplification of cells with suppressor activity.

PMID- 8261795
TI  - Muller cell expression of glial fibrillary acidic protein (GFAP) in RPE-cell
      transplanted retinas of RCS dystrophic rats.
AB  - In Royal College of Surgeons (RCS) rats with inherited retinal dystrophy,
      photoreceptor cell degeneration is accompanied by Muller cell changes, in
      particular, increased expression of the intermediate filament protein, glial
      fibrillary acidic protein (GFAP). In this study, we examined the expression of
      GFAP in retinas of 4 month-old RCS dystrophic rats either transplanted with
      normal retinal pigment epithelial (RPE) cells or injected with vehicle (sham
      control). The sham-injected and non-treated retinas showed increased expression
      of GFAP in Muller cells with advancing age. GFAP-immunostained Muller processes
      were observed in the region of the subretinal space of these RCS retinas
      beginning by 4 months. However, in the retinas of RCS rats transplanted with
      normal RPE cells, GFAP expression by Muller cells was significantly reduced.
      Specifically, under the transplanted RPE cells, GFAP-immunolabeled Muller radial
      processes were not observed and GFAP immunostaining was not present in the
      subretinal space at any time period examined. Immunoblot analysis of the superior
      hemisphere of RPE-cell transplanted retinas of 4 month-old RCS dystrophic rats
      showed less GFAP immunostaining than sham-injected and the inferior hemisphere of
      retinas of age-matched RCS rats. This study showed that in normal RPE-cell
      transplanted retinas of RCS rats, in addition to rescued photoreceptor cells,
      there was an accompanying stabilization of Muller cells as demonstrated by a
      reduction in the expression of GFAP.

PMID- 8261796
TI  - Comparison of uptake and incorporation of docosahexaenoic and arachidonic acids
      by frog retinas.
AB  - Vertebrate retinas, especially photoreceptor cellular membranes, contain high
      levels of docosahexaenoic acid (DHA) and relatively low levels of arachidonic
      acid (AA). The present study was designed to test the hypothesis that DHA
      enrichment in the retina is the result of preferential uptake and incorporation
      relative to other fatty acids. Frog retinas were incubated in vitro with [3H]DHA
      or [3h]AA for up to 6 h, and the amounts of label in retinal lipids were
      quantitated. The incorporation of DHA into total lipids, triglycerides,
      phosphatidylcholine, and phosphatidylethanolamine was similar to that of AA when
      each was presented as the only substrate, and was linear with fatty acid
      concentration and incubation time. The addition of excess, unlabeled AA reduced
      the uptake and incorporation of DHA into retinal lipids. A slightly greater
      inhibition was noted for the uptake and incorporation of AA in the presence of
      unlabeled DHA. There was about 2-3 fold greater incorporation of DHA into
      phosphatidic acid, diglycerides, and phosphatidylinositol compared with AA,
      whereas the reverse was found for phosphatidylserine. The different levels of DHA
      and AA in retinal phospholipids cannot be explained by different rates of uptake
      and incorporation of these fatty acids into lipids, although some slight
      enrichment of DHA may be possible by this mechanism. The linear incorporation
      with fatty acid concentration suggests that the difference could be accomplished
      by controlling the amount and type of fatty acids delivered to the retina by the
      adjacent pigment epithelium.

PMID- 8261797
TI  - Confirmation of the rod cGMP phosphodiesterase beta subunit (PDE beta) nonsense
      mutation in affected rcd-1 Irish setters in the UK and development of a
      diagnostic test.
AB  - Rod/cone dysplasia type one (rcd-1) is an early onset inherited retinal dystrophy
      segregating in the Irish setter breed. It is classed as one of the autosomal
      recessive canine generalised Progressive Retinal Atrophies (PRA). The disease
      results in complete loss of photoreceptors by approximately one year of age.
      Levels of retinal cGMP are markedly elevated and of abnormal distribution in rod
      photoreceptors. Rod phosphodiesterase activity is absent and mRNA encoding the
      beta subunit (PDE beta) of the holoenzyme is uniquely reduced in predegenerate
      retinae. Using retinae from normal, unrelated adult dogs we have PCR-amplified
      and sequenced the cDNA for PDE beta. The cDNA is almost identical to that
      recently described for the Irish setter in the USA apart from two translationally
      silent single nucleotide changes. Using carrier and affected setters from a UK
      breeding colony we have screened genomic DNA and can confirm the G to A
      transition in rcd-1 affected dogs at position 2420, creating an amber mutation in
      codon 807. However, PRA-affected Tibetan terriers and miniature longhaired
      dachshunds are normal at this locus, underlining the genetic heterogeneity of
      this disease group. In addition we have developed a rapid, PCR-based diagnostic
      test for this mutation that will differentiate normal dogs from asymptomatic
      carriers.

PMID- 8261798
TI  - Pulmonary embolic disease: diagnosis, pathophysiologic aspects, and treatment
      with thrombolytic therapy.

PMID- 8261800
TI  - Three helpful hints for patients.

PMID- 8261799
TI  - Transfusion and surgery.
AB  - In this survey of transfusion in surgery, we have attempted to provide the
      surgeon with an understanding of the problems associated with homologous
      transfusion and a practical knowledge of treatment strategies and alternatives
      designed to reduce homologous blood exposure. Such a review cannot be
      encyclopedic. Our hope is that it will serve the reader as a stimulus to examine
      his or her transfusion practices and as a guide for future self-learning.

PMID- 8261801
TI  - The safety of stainless steel hip prosthesis in nickel-sensitive individuals.

PMID- 8261802
TI  - Molluscum contagiosum in children.

PMID- 8261803
TI  - A dermatologic diary. Portrait of a practice.

PMID- 8261804
TI  - Apert's syndrome (acrocephalosyndactyly) in a patient with hyperhidrosis.
AB  - Apert's syndrome, also known as acrocephalosyndactyly, is a rare type of
      premature craniofacial synostosis characterized by the clinical triad of cranial
      and facial malformations along with syndactyly of the hands and feet. Acne
      vulgaris involving atypical sites such as the upper extremities constitutes the
      dermatologic hallmark of this rare genodermatosis. We report a patient who
      demonstrates the classic findings of Apert's syndrome. Our patient also presented
      with severe hyperhidrosis, which may represent a new clinical finding not
      previously reported in association with this syndrome.

PMID- 8261805
TI  - Tinea nigra: treatment with topical ketoconazole.
AB  - Tinea nigra is a relatively uncommon fungal infection presenting as a pigmented
      macule of the palms or soles. Since the lesion can easily mimic a melanocytic
      process, it is important to recognize the infection before recommending
      unnecessary surgical procedures. A case of tinea nigra that responded to
      treatment with topical ketoconazole is presented.

PMID- 8261806
TI  - Hydroxyurea and lower leg ulcers.
AB  - We report four cases of cutaneous lower leg ulcers associated with hydroxyurea
      treatment for myeloproliferative disorders. This association has been reported in
      one other series of patients who had chronic myelogenous leukemia and were
      treated with hydroxyurea. A review of the literature and survey of possible
      pathogenetic mechanisms is presented.

PMID- 8261807
TI  - Cutaneous and visceral granulomas in common variable immunodeficiency.
AB  - A middle-aged woman with common variable immunodeficiency noted a papular skin
      eruption that simulated Gottron's sign of dermatomyositis on the dorsal hands.
      Examination of a skin biopsy specimen demonstrated noninfectious granulomatous
      inflammation. The patient was subsequently found to have visceral granulomas when
      examined using laparotomy. Noninfectious granulomas of the viscera and integument
      have been previously reported in patients with several immunodeficiency
      syndromes, including common variable immunodeficiency.

PMID- 8261808
TI  - Lofgren's syndrome.
AB  - Lofgren's syndrome consists of a triad of erythema nodosum, bilateral hilar
      adenopathy, and arthritis and heralds the acute onset of sarcoidosis. A single
      symptom may be misdiagnosed and mistreated by an unsuspecting physician. We
      present a case of Lofgren's syndrome that was initially believed to be
      cellulitis. We briefly review the course and treatment of Lofgren's syndrome.

PMID- 8261809
TI  - Hand eczema herpeticum.
AB  - Eczema herpeticum consists of a primary herpes simplex virus infection
      superimposed on a pre-existing dermatosis. Localized forms of this condition also
      occur. A twenty-three-year-old woman showed a primary herpes simplex virus
      infection in the areas of her residual atopic hand eczema after contact with her
      eighteen-month-old son's oral cavity, which was infected with herpes simplex type
      I. Possible theories about pathogenesis include a temporary deficit in cell
      mediated immunity, defective interleukin production, or persistent alteration of
      the affected skin. Use of acyclovir resulted in rapid clearing of the eruption.
      Herpes simplex virus infection should be considered in the differential diagnosis
      when a flare or vesiculation occurs in patients with atopic hand eczema.

PMID- 8261810
TI  - Hydroxychloroquine.
AB  - The only antimalarial drug approved by the Food and Drug Administration for the
      treatment of lupus erythematosus is hydroxychloroquine (Plaquenil) sulfate. The
      dosage recommended officially for this disease is vague. Retinopathy has been
      caused by hydroxychloroquine but not in less than six months, nor when a total
      dosage of less than 72 gm or a daily dose of 200 mg or less is used. The ocular
      risk depends on the dose/weight ratio and is almost negligible at a dosage of
      less than 6 mg/kg/day. At a dosage of 400 mg or more daily, the risk/benefit
      ratio is acceptable for a person of average weight, provided that ophthalmologic
      monitoring is adequate. Risk of retinal toxicity is then proportional to duration
      of therapy and consequent cumulative dose. Ophthalmoscopic examinations at six
      month intervals should be sufficient to detect occasional adverse reactions. Such
      tests could be conducted by the attending physician directly, as long as no pre
      existing ocular abnormality exists.

PMID- 8261812
TI  - Welfare reform: a priority for Clinton administration.

PMID- 8261811
TI  - Treatment of pseudofolliculitis barbae with topical glycolic acid: a report of
      two studies.
AB  - Pseudofolliculitis barbae (razor bumps) is a foreign-body inflammatory reaction
      surrounding ingrown facial hair, which results from shaving. The problem occurs
      in persons with curly hair, with an incidence of over 50 percent in black men.
      The objective of the two studies described was to assess the effectiveness of
      topical glycolic acid in the treatment and prevention of razor bumps. The studies
      consisted of two placebo-controlled trials in thirty-five adult men. The results
      showed that glycolic acid lotion was significantly more effective than placebo in
      treating pseudofolliculitis barbae. There was over a 60 percent reduction in
      lesions on the treated side, which allowed daily shaving with little irritation.
      Topical application of glycolic acid lotion is an effective therapy for
      pseudofolliculitis barbae and allows the patient to resume a daily shaving
      regimen.

PMID- 8261813
TI  - Serum alanine aminotransferase (ALT) elevation in asymptomatic US Air Force basic
      trainee blood donors.
AB  - The purpose of this study was to determine the etiology of elevated alanine
      aminotransferase (ALT) in a population of asymptomatic volunteer blood donors.
      Subjects with an ALT value > 2.25 sd above norm (> 55 IU/liter) from the donated
      unit, were prospectively evaluated over a six-week interval. The subjects
      consisted of blood donors (78% male, 22% female) beginning basic military
      training at Lackland Air Force Base. Of 44,160 individuals screened, 19,877 (45%)
      voluntarily donated blood, 99 (0.5%) of which had confirmed ALT elevation. Of
      these (90 male/9 female), an associated condition or explanation was made in 12%:
      four with acute hepatitis B, four positive for anti-HCV, two with autoimmune
      disease, one with cholelithiasis and one associated with acute appendicitis. In
      87 the ALT elevation could not be explained using available testing methods but
      may represent individual variation from a non-Gaussian distribution, be of
      nonhepatic origin (muscle), or of hepatic disease not detected by the diagnostic
      algorithm used. To increase the diagnostic yield, it is suggested that at least
      two elevated ALT values be established in this population over a period of time
      (yet undefined), before an extensive hepatic investigation is pursued.

PMID- 8261814
TI  - Prevalence of hepatitis C virus infection in asymptomatic anti-HIV1 negative
      pregnant women and their children.
AB  - The prevalence of hepatitis C virus (HCV) infection was studied prospectively in
      pregnant women in France and their children by detection of anti-HCV with second
      generation ELISA (ELISA2). In ELISA2-positive women, anti-HCV was detected with
      second- and third-generation RIBA (RIBA2 and RIBA3) and serum HCV RNA was
      detected with PCR. Among 670 women, anti-HIV1-negative, 26 (3.9%) were positive
      with ELISA2. RIBA2 was positive in 13 and HCV RNA was found in 10. Ten ELISA2
      positive women had a further evaluation with assessment of HCV infection in their
      children. Among the 10 children born to the index pregnancy, only one was
      positive with ELISA2 and RIBA2 but negative with RIBA3 and PCR; the nine other
      children were ELISA2, RIBA2, RIBA3, and PCR negative. All 26 siblings (2-16 years
      old), of whom 14 were born to PCR-positive mothers, were ELISA2 and RIBA2
      negative. We conclude that among anti-HIV1-negative pregnant women with normal
      serum ALT levels, the prevalence of HCV infection is relatively high but the risk
      for mother-to-infant transmission of HCV seems to be low.

PMID- 8261815
TI  - Quantitative detection of hepatitis B virus DNA in sera from patients with acute
      hepatitis B.
AB  - Two hundred forty-four serial serum samples from 30 adults hospitalized with
      benign (nonfulminant) acute hepatitis B were tested for the presence of hepatitis
      B virus (HBV) DNA by a quantitative solution hybridization assay using a 125I
      labeled DNA probe complementary to HBV-DNA sequences. Acute hepatitis B was self
      limiting in 28 and progressed to chronicity in the remaining two patients. Of the
      28 patients with self-limiting hepatitis, 21 (75%) were hepatitis B e antigen
      (HBeAg) positive, 26 (93%) were HBV-DNA positive, and one patient (3.6%) was
      negative for both markers on admission to the hospital. HBV-DNA cleared after
      HBeAg clearance in 20 (71.4%), before HBeAg clearance in five (17.9%) and
      simultaneously with the loss of HBeAg in the remaining two (7.1%) of the 27
      initially HBV-DNA- and/or HBeAg-positive patients. Moreover, HBV-DNA remained
      detectable in serum for 13.3 +/- 6.6 (range: 4-22) days after the appearance of
      anti-HBe in 71.4% of these patients. In contrast, HBV-DNA and HBeAg remained
      persistently positive in the two patients who developed chronic HBV infection.
      These data show that (1) viremia frequently persists after disappearance of HBeAg
      and (2) appearance of anti-HBe does not indicate the cessation of HBV replication
      in adults with acute self-limiting hepatitis B.

PMID- 8261816
TI  - Effect of lidocaine on in vivo hepatic function.
AB  - Lidocaine is administered to assess donor or recipient liver function during
      hepatic transplantation. This study was performed to determine whether lidocaine
      administered at a constant concentration affected hepatic function or had
      demonstrable effects on hepatocellular ultrastructure. Fourteen pigs were
      randomly allocated to receive either a two-stage infusion of lidocaine
      hydrochloride or of saline. Transhepatic blood samples were taken and ultrasonic
      portal venous and hepatic arterial blood flow readings made on animals
      anesthetized with isoflurane in nitrous oxide. Liver biopsies were taken for
      histological analysis and determination of adenine nucleotide status prior to and
      after 2 hr of the two-stage infusion. A mean systemic constant plasma lidocaine
      concentration of 5.9 micrograms/ml was achieved during the second hour of
      infusion. There were no differences between the two groups in a large number of
      indices of hepatic function and plasma composition prior to and during the second
      hour of the respective infusions. Hepatic blood flow was also similar at these
      times. On histological examination there were no electron microscopic changes
      that could be specifically attributed to the administration of lidocaine.
      However, there were progressive changes with time. This study suggests that in
      anesthetized pigs a constant lidocaine concentration of about 6 micrograms/ml has
      no detrimental effect on hepatic function. Progressive hepatic ultrastructural
      changes occurred that could not be attributed to the administration of lidocaine.
      These may be the result of anesthetic administered or the surgery performed.

PMID- 8261817
TI  - Hepatic [14C]aminopyrine demethylation capacity after portocaval shunting.
      Comparative study in patients with and without arterialization of portal vein.
AB  - The [14C]aminopyrine breath test (ABT) was used before and after surgical
      portocaval shunting in 29 cirrhotic patients, 15 with arterialization of the
      portal vein and 14 without. These two subgroups were comparable with regard to
      age, prothrombin time, serum albumin, serum total bilirubin concentrations, Child
      classification, and preoperative ABT. After portocaval shunt, a striking
      reduction in ABT values was observed after 6 and 12 months (90.7 +/- 8.0%, P <
      0.05 and 77.3 +/- 7.5%, P < 0.005, respectively). No further decrease was
      observed between 12 and 24 months. The microsomal function was reduced to a
      greater extent in patients with postnecrotic cirrhosis (55 +/- 4.8%, P < 0.01)
      than in those with alcoholic cirrhosis (84.8 +/- 10.4%, P < 0.05).
      Arterialization of the portal stump of the portal vein did not prevent the
      reduction in hepatocellular function. No significant change in prothrombin time,
      serum albumin, or bilirubin concentrations was observed during the follow-up
      period in any of the groups. Overall, preoperative ABT was significantly higher
      in those surviving one year (0.29 +/- 0.12% administered dose) than in those who
      died within this time period (0.12 +/- 0.01%, P < 0.005). This observation
      suggests that portocaval anastomosis induces an early decrease in microsomal
      function that is not prevented by arterialization of the portal vein. It also
      suggests that ABT might be helpful in selecting patients for shunt surgery.

PMID- 8261818
TI  - Measurement of functioning hepatocyte mass via [99mTc]galactosyl-neoglycoalbumin.
AB  - Technetium-99m-galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled
      ligand specific for hepatic binding protein (HBP), a receptor that resides
      exclusively on hepatocytes. In vivo measurement of receptor concentration was
      obtained via kinetic analysis of liver and blood time-activity data obtained
      during the hepatic clearance of intravenously administered TcNGA. The purpose of
      this study was to assess receptor concentration as a measure of the functioning
      hepatocyte mass. Therefore, TcNGA and dual-injection indocyanine green maximal
      removal rate (ICG Rmax) studies were performed on nine patients with hepatic
      cirrhosis associated or not with hepatocellular carcinoma. Receptor concentration
      was compared with ICG Rmax, which is a validated method for the estimation of the
      functioning hepatocyte mass. The correlation coefficient was 0.76 (P = 0.017). It
      is concluded that HBP concentration ([HPB]o) as measured by functional imaging is
      a measure of functioning hepatocyte mass. This implies that measurement of an
      individual's receptor concentration by using nuclear medicine techniques provides
      an objective index of hepatic functional mass and supports attempts to rigorously
      evaluate [HBP]o for its clinical efficacy.

PMID- 8261819
TI  - Effect of flushing of the liver graft upon plasma calcium and magnesium
      concentrations.
AB  - Previous studies of total and ionized calcium in the plasma of liver transplant
      recipients have been conducted in patients with preexisting liver disease or who
      received blood transfusion. The intraoperative decline in plasma total and
      ionized calcium has been attributed to the effects of liver disease and/or the
      citrate in transfused blood. The present study was conducted in normal porcine
      recipients of liver stored either with EuroCollins or University of Wisconsin
      (UW) solution for 6 hr, compared with livers flushed with Ringer's lactate
      without storage. No blood transfusion was given. Mean total plasma calcium levels
      declined significantly after storage with UW solution to a nadir approximately 65
      70% of preoperative levels. This decline persisted for two to five days. Mean
      levels of plasma ionized calcium declined lowest after flushing with UW solution
      but only to 82% of preoperative (NS). There was an increase in plasma total
      magnesium in the recipients of livers flushed with EuroCollins or UW solutions,
      which resolved within 30 min and which was probably related to magnesium content
      of the flushing solution. It is concluded that while the changes in plasma total
      and ionized calcium are moderate and of little clinical significance, they could
      be aggravated under clinical conditions by massive blood transfusion. Changes in
      plasma magnesium seemed to be directly attributable to the magnesium content of
      flushing solutions but the same relationship did not exist for changes in plasma
      calcium.

PMID- 8261820
TI  - Hemodynamic characterization in experimental liver cirrhosis induced by
      thioacetamide administration.
AB  - Systemic and splanchnic hemodynamics in experimental liver cirrhosis in rats
      induced by thioacetamide were evaluated by the radioactive microsphere method.
      Cardiac output and regional blood flow were measured in conscious and
      anesthetized control and cirrhotic rats. The conscious thioacetamide-treated rats
      had hyperdynamic circulation with an increased cardiac index (300 +/- 10 vs 258
      +/- 3 ml/min/kg body weight, P < 0.001) and increased portal venous inflow
      compared with the controls (64.60 +/- 2.4 vs 48.39 +/- 0.88 ml/min/kg body
      weight, P < 0.001). Under pentobarbital anesthesia, the hyperdynamic circulation
      of the cirrhotic rats was maintained, with an increased cardiac index (276 +/- 7
      vs 229 +/- 5 ml/min/kg body weight, P < 0.001) and increased protal venous inflow
      compared with the controls (72.47 +/- 3.0 vs 54.08 +/- 1.2 ml/min/kg body weight,
      P < 0.001). Portal pressure, portal venous resistance, and portal systemic
      shunting increased significantly while splanchnic arterial resistance decreased
      significantly in cirrhotic rats. Thioacetamide-induced cirrhosis is a useful
      model for the hemodynamic study of portal hypertension and remains useful in
      hemodynamic studies in the basal state under pentobarbital anesthesia.

PMID- 8261821
TI  - Portal hypertension. Its effects on gastric function and ethanol-induced gastric
      mucosal damage in rats.
AB  - The time-course effects of portal hypertension on gastric secretory function,
      mucosal blood flow, vascular permeability, and ethanol-induced gastric mucosal
      damage were examined in anesthetized rats. Partial ligation of the portal vein
      effectively produced portal hypertension one to three days later but the raised
      pressure returned to normal on the sixth day after ligation. This time-course
      effect coincided with reduced pepsin secretion and mucosal blood flow and also
      with potentiated ethanol-induced mucosal damage during the first to third days.
      These effects started to tail off on the sixth day. However, gastric acid output
      was significantly reduced on the third day, and this was strongest on the sixth
      day after operation. Portal vein ligation also reduced basal vascular
      permeability, which was markedly potentiated after ethanol treatment. It is
      concluded that: (1) portal vein blood pressure changes are a time-dependent
      process following ligation; (2) changes in gastric mucosal blood flow (GMBF) and
      lesion formation are closely related to portal hypertension; (3) gastric mucosal
      injury is associated with vascular damage, as evidenced by increased in vascular
      permeability; and (4) pepsin but not acid secretion is closely related to the
      state of the GMBF.

PMID- 8261822
TI  - Midazolam sedation for percutaneous liver biopsy.
AB  - Control of patient respiration is needed to safely perform percutaneous liver
      biopsy (PLB) and may be adversely affected by sedation. The purpose of this study
      was to evaluate the safety of PLB with intravenous midazolam and to evaluate
      patient acceptance of PLB with and without sedation. Two hundred seventeen
      consecutive patients underwent 301 percutaneous liver biopsies. One hundred fifty
      one of the biopsies were done after the patients were sedated with intravenous
      midazolam immediately before the biopsy. The last 61 patients were questioned
      after the biopsy to evaluate the discomfort of the procedure, their memory of the
      procedure, and their willingness to undergo another PLB. The major complication
      rate was similar in the midazolam-treated (0.7%) and untreated (0.7%) groups. The
      midazolam-treated patients had a numerically lower mean pain score (1.5 +/- 0.4
      vs 4.0 +/- 0.7) (mean +/- SEM) (P = 0.07) and significantly lower mean memory
      score (4.8 +/- 0.7 vs 9.9 +/- 0.1) (P < 0.01) than the untreated patients. The
      treated and untreated groups had similar mean willingness for repeat PLB scores
      (9.3 +/- 0.3 vs 9.1 +/- 0.6). We conclude that: (1) there is no increased risk of
      PLB with midazolam and (2) patients have less memory of the procedure with
      midazolam.

PMID- 8261823
TI  - Laparoscopic cholecystectomy. Postoperative sonographic findings.
AB  - Seventeen consecutive patients undergoing elective laparoscopic cholecystectomy
      (LC) were serially evaluated with transabdominal ultrasound before, one day
      after, and six days after LC to document what, if any, changes occur in the
      surgical bed and surrounding parenchyma. The most common postoperative finding
      was focal sonolucency in the hepatic parenchyma adjacent to the gallbladder fossa
      in six (35%) of 17 patients. Five patients (29%) had postoperative fluid
      collections in the gallbladder fossa; in four of these five, it was technically
      difficult to dissect the gallbladder from the liver at the time of original
      surgery. In one patient the fluid resolved by the sixth postoperative day. It
      persisted in the remaining four. Two patients had transient ductal dilation and
      one had pneumobilia. Shadowing and ring-down artifact was identified in 12
      patients due to surgical clips in the triangle of Calot. Because gallbladder
      fossa fluid may persist up to six days after uncomplicated laparoscopic
      cholecystectomy, caution should be used before attaching significance to isolated
      imaging findings. Clinical judgement remains the best means of selecting which
      patients need additional evaluation.

PMID- 8261824
TI  - Relationship between cystic duct diameter and the presence of cholelithiasis.
AB  - We sought to measure cystic duct diameter in patients without biliary calculi and
      in those with cholelithiasis or choledocholithiasis. Using endoscopic retrograde
      cholangiopancreatography (ERCP), we visualized the cystic duct in 168 patients
      referred to our unit. These patients were distributed into three groups based on
      findings at ERCP: Group I (N = 57), no calculi in the gallbladder or common bile
      duct; group II (N = 27), stones found in the gallbladder but absent from the
      common bile duct; and group III (N = 34), stones present in the common bile duct
      with or without gallbladder stones. The diameter of the cystic duct was measured
      at its widest and narrowest dimensions. The largest diameter measured was greater
      in group III (7.72 +/- 2.29 mm) than in groups I (2.63 +/- 0.67 mm) and II (4.59
      +/- 1.13 mm) (P < 0.001). The same differences were found in measurement of the
      smallest diameter (5.00 +/- 0.99 mm, 3.10 +/- 0.62 mm, and 1.83 +/- 0.53 mm, for
      groups III, II, and I, respectively) (P < 0.001). Maximal and minimal cystic duct
      diameter show a progressive increase at each level of disease. This increase in
      cystic duct size may facilitate the migration of gallstone fragments after
      lithotripsy and facilitate the instrumentation of the cystic duct during ERCP and
      laparoscopic cholecystectomy.

PMID- 8261825
TI  - Endoscopic sphincterotomy for common bile duct calculi in patients without stones
      in the gallbladder.
AB  - Endoscopic sphincterotomy (ES) was performed in 25 patients for common bile duct
      (CBD) calculi in the absence of stones in the gallbladder. Eighteen of these
      patients were considered unfit for surgery because of age or concomitant disease.
      All ES procedures were technically successful with complete evacuation of the CBD
      in all cases. Early complications occurred in only one patient, a 91-year-old
      female who died from nonbiliary tract disease. Long-term follow up over a period
      of 42 months was available in 19 of the 24 patients. Late complications occurred
      in two patients (10%), both of whom developed cholecystitis; they underwent
      surgery without subsequent morbidity or mortality. This 10% incidence of long
      term complications is similar to that of other series that did not differentiate
      between patients with isolated CBD calculi and those with stones also present in
      the gallbladder. The observed complication rate does not justify routine
      prophylactic cholecystectomy after ES for isolated CBD stones.

PMID- 8261826
TI  - Hyperglycemia modulates gallbladder motility and small intestinal transit time in
      man.
AB  - The aim of the present study was to investigate the effect of acute hyperglycemia
      on (1) the intestinal phase of gallbladder contraction induced by the
      intraduodenal administration of emulsified fat, and (2) the small intestinal
      transit time measured by the lactulose breath hydrogen test. Six healthy
      volunteers were studied in random order during normoglycemia and hyperglycemia
      (blood glucose levels 15 mmol/liter). Gallbladder volumes were measured with
      ultrasonography. Administration of 1 and 2 g/hr of fat resulted in significant
      reductions in gallbladder volumes from 24 +/- 2 cm3 to 11 +/- 1 cm3 (P < 0.05)
      and 8 +/- 1 cm3 (P < 0.05), respectively during normoglycemia, and from 24 +/- 2
      cm3 to 21 +/- 2 cm3 (P < 0.05) and 16 +/- 2 cm3, respectively (P < 0.05) during
      hyperglycemia. Compared to normoglycemia, the gallbladder contraction was
      significantly (P < 0.05) reduced during hyperglycemia. No significant differences
      in CCK secretion were observed between experiments. Small intestinal transit time
      during hyperglycemia (101 +/- 12 min) was significantly (P < 0.05) prolonged
      compared to normoglycemia (57 +/- 12 min). During hyperglycemia, basal PP levels
      and PP secretion in response to intraduodenal fat were significantly (P < 0.05)
      reduced compared to normoglycemia. It is concluded that (1) low doses of
      intraduodenal emulsified fat result in significant gallbladder contraction and
      CCK secretion, (2) acute hyperglycemia inhibits intraduodenal fat induced
      gallbladder contraction, (3) acute hyperglycemia does not affect the
      intraduodenal fat induced CCK secretion, (4) small intestinal transit is
      significantly prolonged during acute hyperglycemia, and (5) acute hyperglycemia
      inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal
      cholinergic tone during hyperglycemia.

PMID- 8261827
TI  - 5-hydroxytryptamine 3-receptor antagonist modulates gallbladder emptying and
      motilin release induced by erythromycin.
AB  - In the present study we evaluated the effect of ondansetron (formerly indicated
      as GR38032F), a potent and selective type-3 5-hydroxytryptamine receptor
      antagonist, on erythromycin-induced gallbladder emptying and motilin release, as
      well as gallbladder emptying induced by a regular meal in healthy volunteers.
      Gallbladder emptying was evaluated by sonography. Ondansetron, at the dose of
      0.05 mg/kg, significantly reduced (P < 0.001 by ANOVA) the gallbladder emptying
      induced by 2 mg/kg/hr erythromycin, but did not increase basal gallbladder volume
      or inhibit gallbladder emptying induced by a regular meal. Ondansetron also
      inhibited the motilin release induced by erythromycin (P < 0.001, by ANOVA).
      These results suggest that serotoninergic mechanisms modulate the effects of
      erythromycin on the gastrointestinal tract. The exact site of action of
      ondansetron remains to be identified.

PMID- 8261828
TI  - Cerebral evoked potentials. A method of quantification of central nervous system
      response to esophageal pain.
AB  - Cerebral evoked potentials (EPs) represent a new technique for the evaluation of
      afferent outflow from the gastrointestinal tract. We compared EPs obtained with
      distension of the distal and proximal esophagus. Responses were recorded with the
      balloon 5 cm proximal to the lower esophageal sphincter and 3 cm distal to the
      upper esophageal sphincter. Balloon stimulation resulted in cortical responses
      recorded by midline scalp electrodes (CZ', PZ, and OZ by the International 10-20
      system) in normal volunteers. EP responses consisted of two negative (N1, N2) and
      one positive (P1) deflections. The proximal esophageal latency of N1 was shorter
      in all three leads. The latency to P1 was shorter with proximal stimulation in
      lead CZ' only, and N2 latencies were not different. Amplitudes expressed as the
      difference between N1 and P1, and P1 and N2 were not different. When two sets of
      potentials several minutes apart from the proximal position were compared, a
      decrease in amplitude with the second set of stimulations was noted. Esophageal
      EP recording is a new technique that may provide information about the integrity
      and function of the sensory innervation of the esophagus.

PMID- 8261829
TI  - Intragastric distribution and gastric emptying of solids and liquids in
      functional dyspepsia. Lack of influence of symptom subgroups and H. pylori
      associated gastritis.
AB  - The relative contributions of altered gastric motor function and Helicobacter
      pylori-associated active chronic gastritis to the pathogenesis of functional
      dyspepsia are controversial. We therefore evaluated scintigraphically the
      intragastric distribution and gastric emptying of a mixed solid-liquid meal in 75
      patients with functional dyspepsia; patients were subdivided on the basis of both
      specific symptom clusters and the presence or absence of H. pylori gastritis.
      Twenty-one (28%) patients displayed abnormal solid and/or liquid gastric
      emptying, with prolonged solid lag time the most prominent alteration detected.
      The number of patients with abnormal scintigraphic patterns increased to 36 (48%)
      when intragastric distribution parameters (fundal half-emptying time and antral
      maximal fraction) were examined. Although patients with reflux-like dyspepsia (N
      = 36) demonstrated significantly slower rates of liquid emptying at 45 and 70 min
      and a higher prevalence of abnormal liquid intragastric distribution when
      compared to patients with motility-like dyspepsia (N = 39) or to controls (N =
      34), the absolute differences were small and unlikely to be of clinical
      significance. Patients without H. pylori gastritis (N = 50) demonstrated a
      significantly more prolonged solid lag time when compared to those with H. pylori
      gastritis (N = 25), but the difference was small and there were no other
      differences between these two subgroups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261830
TI  - Different interdigestive antroduodenal motility patterns in chronic antral
      gastritis with and without Helicobacter pylori infection.
AB  - Fasting antroduodenal motor activity was studied in 15 dyspeptic patients with
      chronic superficial antral gastritis and Helicobacter pylori infection (group A),
      10 dyspeptic patients with chronic superficial antral gastritis without
      Helicobacter pylori infection (group B), and eight healthy control subjects
      (group C) by manometric recording of phases of the interdigestive migrating motor
      complex (MMC) prolonged over 240 min. A significantly lower incidence of activity
      fronts (phase III of MMC) starting from the antrum was observed in patients with
      gastritis and Helicobacter pylori infection vs patients without bacterial
      colonization (P = 0.013) and in these latter vs control subjects (P = 0.013).
      Likewise, the overall number of activity fronts was smaller in patients with
      gastritis than in healthy subjects (P = 0.034). Symptomatic evaluation was
      performed in the two groups of dyspeptic patients, without detecting any
      differences in frequency and severity of complaints. Our results show a
      significant reduction in the occurrence of interdigestive antral phase III of MMC
      in chronic gastritis associated with Helicobacter pylori infection, suggesting a
      possible relationship between fasting motility and bacterial colonization.

PMID- 8261831
TI  - Role of Helicobacter pylori serology in evaluating treatment success.
AB  - Duodenal ulcer recurrence and gastritis are reduced with successful Helicobacter
      pylori treatment. Serology is accurate in the diagnosis of H. pylori, but its
      value in determining eradication is unproved. To evaluate the usefulness of
      serology in monitoring treatment, we measured serial serum antibodies in three
      patient groups: eradication success (N = 57), eradication failure (N = 19), and
      untreated patients (N = 24). Eradication was determined by Warthin Starry
      staining of antral biopsies and repeat 13C breath tests at six weeks. Subsequent
      13C breath tests were then performed at three-month intervals to monitor
      eradication. IgG antibody concentrations to H. pylori were determined by a
      commercially available ELISA kit. Serology concentrations remained constant
      throughout the study period in the untreated patients. IgG concentrations
      decreased slightly in the treatment failure group at six weeks but thereafter
      remained at baseline values. In the eradicated group, serum IgG concentrations
      decreased 26% by three months, 43% by six months and 55% at nine and 12 months (P
      < 0.001). A 20% reduction in IgG concentrations by six months was associated with
      successful treatment (sensitivity 86% and specificity 88%). We conclude that
      serology is a potentially useful way to monitor H. pylori treatment success.

PMID- 8261832
TI  - Intestinal fat digestion plays a significant role in fat-induced suppression of
      gastric acid secretion and gastrin release in the rat.
AB  - We have investigated the role of intestinal fat digestion in fat-induced
      suppression of gastric acid secretion and gastrin release in the rat.
      Intraduodenal administration of oleic acid (10%, pH 6.5) and triglyceride (10%,
      pH 6.5) at a rate of 2 ml/hr resulted in significant suppression of gastric acid
      secretion and gastrin release stimulated by intragastric perfusion of peptone
      (0.5%). Diversion of pancreatic juice from the duodenum completely abolished
      triglyceride-induced inhibition of peptone-stimulated gastric acid secretion and
      plasma gastrin release, but oleic acid-suppressed gastric acid secretion and
      gastrin release were unaffected by pancreatic juice diversion. Intraduodenal
      administration of digested triglyceride, prepared by preincubation with lipase,
      caused significant suppression of the peptone-induced gastric acid secretion and
      rise in plasma gastrin levels, even though pancreatic juice was excluded. The
      results of this study indicate that digestive products of triglyceride by
      pancreatic juice, especially by lipase, are responsible for the intestinal fat
      induced inhibition of gastric acid secretion and gastrin release and that
      intestinal fat digestion plays a significant role in the mechanism.

PMID- 8261833
TI  - Caco-2 cell metabolism of oxygen-derived radicals.
AB  - Reactive oxygen metabolites have been associated with gastrointestinal injury and
      may play a role as mediators of inflammation. The effect of oxygen metabolites on
      Caco-2 cell viability (trypan blue exclusion and 51Cr release), hexose
      monophosphate shunt activity, and glutathione was assessed. Caco-2 cells were
      incubated with amino acid oxidase, xanthine oxidase, menadione, and t
      butylhydroperoxide in the presence and absence of superoxide dismutase, catalase,
      mannitol, and butylated hydroxytoluene. With amino acid oxidase, trypan blue
      exclusion decreased (P < 0.01) and 51Cr release, oxidized glutathione, and shunt
      activity increased (P < 0.05). The addition of catalase attenuated these changes.
      Trypan blue exclusion decreased (P < 0.005) and 51Cr release, oxidized
      glutathione, and shunt activity increased (P < 0.01) with xanthine oxidase. The
      addition of superoxide dismutase caused a further increase in 51Cr release,
      oxidized glutathione, and shunt activity (P < 0.01), which was prevented by the
      addition of catalase or mannitol. t-Butylhydroperoxide did not effect 51Cr
      release or trypan blue exclusion, but oxidized glutathione and shunt activity
      increased (P < 0.01). The increase in shunt activity was prevented by
      preincubation with butylated hydroxytoluene (P < 0.01). Menadione did not alter
      trypan blue exclusion or 51Cr release, but caused an increase in oxidized
      glutathione and shunt activity (P < 0.001). The increase in shunt activity was
      attenuated by preincubation with butylated hydroxytoluene (P < 0.001). Menadione
      also caused a depletion of total glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261834
TI  - Gastric ulcers differ from duodenal ulcers. Evaluation of basal acid output.
AB  - Patients with pyloric channel and prepyloric gastric ulcers are often considered
      to have an ulcer diathesis similar to patients with duodenal ulcers, while
      patients with more proximal gastric ulcers (ie, fundus, body, antrum) are
      excluded. To evaluate possible differences in basal acid outputs with regard to
      gastric ulcer location, basal acid outputs were determined by nasogastric suction
      in 80 patients with endoscopically documented benign active gastric ulcers. The
      results were compared to 65 normal subjects and 155 patients with endoscopically
      documented duodenal ulcers. There were no significant differences in basal acid
      outputs among the 80 patients with gastric ulcers with regard to location (ie,
      fundus-body, antrum, prepyloric, channel), and no significant differences
      compared to the 65 normal subjects. However, basal acid output for the 155
      patients with duodenal ulcers was significantly different from the 80 patients
      with gastric ulcers (P < 0.05) and the 65 normal subjects (P < 0.05). Basal acid
      outputs tended to be higher and there was more gastric acid hypersecretion when
      gastric ulcers were located near the pylorus. However, irrespective of gastric
      ulcer location, basal acid outputs were higher in patients with duodenal ulcers.
      Seventy-one of the 80 patients with gastric ulcers were treated for eight weeks
      with standard doses of antisecretory medications, and endoscopic healing or
      nonhealing was documented. In 60 patients their gastric ulcers completely healed,
      while 11 patients had nonhealed gastric ulcers. There were no significant
      differences between the two groups with regard to gender, mean age, or basal acid
      output.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261835
TI  - Efficacy of famotidine 20 mg twice a day versus 40 mg twice a day in the
      treatment of erosive or ulcerative reflux esophagitis.
AB  - Two different doses of famotidine (20 mg twice a day versus 40 mg twice a day)
      were evaluated in a double-blind, randomized multicenter study in 474 symptomatic
      patients with erosive ulcerative reflux esophagitis. A total of 238 patients were
      treated with famotidine 20 mg and 236 patients with 40 mg at breakfast and dinner
      time. Relief of symptoms was significant in all patients after six and 12 weeks
      and not different in both treatment groups. Overall endoscopic healing was
      significantly better in the famotidine 40 mg twice a day group compared with 20
      mg twice a day at week 6 (58% versus 43%; P < 0.05) and at week 12 (76% versus
      67%; P < 0.05). Extending treatment to 24 weeks with 40 mg of famotidine twice a
      day in those patients not healed after 12 weeks did not result in further symptom
      relief or in significantly better overall healing. The differences in efficacy of
      these two doses were more pronounced with increasing severity of esophagitis.
      Analyzed by grade of esophagitis at entrance, healing was significantly better
      with famotidine 40 mg twice a day at week 6 for grade II, at week 12 for grades
      III and IV, and at week 24 for grade IV esophagitis. The results show that in the
      treatment of erosive/ulcerative reflux patients famotidine 40 mg twice a day is
      more effective and achieves faster healing than famotidine 20 mg twice a day.

PMID- 8261836
TI  - Adverse effects of vagotomy on ethanol-induced gastric injury in the rat. Absence
      of a role for glutathione redox cycle.
AB  - Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced
      gastric injury and prevent the occurrence of adaptive cytoprotection against such
      injury by a mild irritant. This study was undertaken to determine whether
      aberrations in glutathione (GSH) metabolism were responsible for these vagotomy
      induced effects. Fasted rats (6-8/group) were subjected to truncal vagotomy and
      pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2
      ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes
      following such treatment, animals were either sacrificed or orally received 2 ml
      of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each
      experimental group, stomachs were removed and either evaluated macroscopically
      for the degree of injury involving the glandular gastric epithelium or samples of
      the mucosa were prepared for measurement of total GSH levels or GSH peroxidase
      (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline
      treatment prior to 100% EtOH exposure resulted in injury to the glandular
      epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100%
      EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH
      elicited almost three times the amount of injury observed in the nonvagotomized
      state and the protective effect of 25% EtOH pretreatment was prevented. Effects
      of the various treatment modalities on GPX and GRT activity were not
      significantly different from control values. When mucosal GSH results were
      plotted against the presence or absence of gastric injury among the various
      groups studied, no significant correlation was apparent.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8261837
TI  - Morphometric analysis of mucous granule depletion and replenishment in rat colon.
AB  - Computer-assisted morphometric analysis was used to quantify mucous granule
      discharge and the subsequent replenishment of secretory granules in the rat colon
      following cholinergic challenge. Within 5 min of stimulation (250 micrograms/kg
      carbachol, subcutaneous), the volume of intracellular mucous granules decreased
      to 61.5% of the control. The apical plasma membranes of goblet cells in the
      midcrypt region became deeply cavitated, indicating that they had accelerated
      mucous granule secretion by a process of compound exocytosis. Goblet cells at the
      base of the crypt rarely showed cavitated apical membranes but clearly became
      depleted of intracellular mucous granules. At 60 min after stimulation, cavitated
      profiles were very rare (< or = 0.4%) but intracellular stores of mucous granules
      were still significantly depressed (54.7% of control). By 4 hr after stimulation,
      mucous granule stores recovered to 94.9% of control levels. Morphometric
      quantification was found to be a reliable and sensitive measure of recent goblet
      cell secretory activity.

PMID- 8261838
TI  - Transluminal ligation of bleeding angiodysplasia of the small bowel without need
      for surgical resection.

PMID- 8261839
TI  - Cytomegalovirus infection associated with onset of inflammatory bowel disease.

PMID- 8261840
TI  - Communication and cytopathology--Part III: Shared responsibility for quality
      improvement.

PMID- 8261841
TI  - Cytology of Mollaret meningitis.
AB  - The diagnosis of Mollaret meningitis was established by cytologic examination of
      the cerebrospinal fluid (CSF) in a patient with recurrent aseptic meningitis. The
      characteristic features of the "Mollaret cell," an activated monocyte, are
      presented; theories of etiology are reviewed.

PMID- 8261842
TI  - Immunocytochemical detection of carcinoembryonic antigen in fine-needle aspirates
      from patients with diverse breast diseases.
AB  - Fine-needle aspirates and paraffin-embedded tissue sections from 91 cases with
      diverse breast diseases were immunostained with carcinoembryonic antigen (CEA)
      monoclonal antibody using a BioGenex StrAviGen kit based on the biotin
      streptavidin amplified methodology. The results were compared with
      histopathologic tumor type and tumor stage. CEA was not expressed in fibrocystic
      changes with mild or florid epithelial hyperplasia (n = 23) and fibroadenomas (n
      = 8). On the other hand, 90% (56/60) of primary breast carcinomas showed positive
      cytoplasmic staining for CEA. No correlation was found between CEA expression,
      histopathologic tumor type, and tumor stage. We suggest that CEA
      immunocytochemistry will help in the accurate diagnosis of primary breast
      carcinoma in fine-needle aspirates in addition to the usual cytological criteria.

PMID- 8261843
TI  - Fine-needle aspiration diagnosis of intra-thoracic and intra-abdominal lesions:
      review of experience in the pediatric age group.
AB  - Review of fine-needle aspiration (FNA) smears from 121 pediatric patients with
      intra-thoracic and intra-abdominal lesions revealed 42 (34.7%) cases of
      neoplasms, 35 (28.9%) cases of tuberculosis, 12 (9.9%) cases of non-tuberculous
      inflammations, 4 (3.3%) cases of benign cystic lesions, and 28 (23.1%)
      inadequate/inconclusive cases. The age of the patients ranged from 20 days to 18
      yr. Ultrasound and/or CT study done in 105 cases localized the lesions in
      following common sites: lungs (19 cases), mediastinum (22 cases), liver (14
      cases), intestines (11 cases), and lymph nodes (17 cases). The neoplastic lesions
      consisted of 39 malignant, one suspicious, and two benign neoplasms. Among the
      neoplasms, the small round cell tumors were the most frequent (27 cases),
      followed by germ cell tumors (eight cases) and miscellaneous neoplasms (seven
      cases). The common small round cell tumors were non-Hodgkins lymphoma (eight
      cases), hepatoblastoma (seven cases), neuroblastoma (five cases), and
      nephroblastoma (three cases). A combined clinical, imaging, and FNA cytology
      approach was found to be useful in arriving at a tissue diagnosis.

PMID- 8261844
TI  - Specimen adequacy evaluation in gynecologic cytopathology: current laboratory
      practice in the College of American Pathologists Interlaboratory Comparison
      Program and tentative guidelines for future practice.
AB  - Routine specimen adequacy evaluation, as advocated by The Bethesda System (TBS),
      can play an important role in improving the sensitivity and accuracy of cervical
      cytopathology screening. The effectiveness of this measure, however, has been
      limited by the lack of uniform criteria for adequacy. Practice parameters are now
      emerging, through TBS development of tentative criteria and interlaboratory
      comparison of adequacy practices. This study reviews 1) nationwide responses to
      surveys of laboratory practices in the College of American Pathologists
      Interlaboratory Comparison Program in Cervicovaginal Cytology (CAP PAP); 2) the
      definitions of adequacy based on TBS; and 3) the results of implementation of
      these criteria in a private independent laboratory, university hospital
      laboratory, and private nonprofit hospital laboratory. In the initial CAP PAP
      survey in 1990, 35% of responding laboratories routinely reported specimen
      adequacy, increasing to 66% in 1991 and 85% in 1992. Interlaboratory variations
      in adequacy practices were observed, however, underscoring the need for consensus
      criteria. The experience in the authors' laboratories indicates that TBS criteria
      can serve as a sound guideline. Effective implementation of adequacy assessment
      in the individual laboratory requires careful attention to ensuring the quality
      of adequacy ratings, correlating clinical and prior laboratory information,
      issuing clear and concise reports, and giving recommendations judiciously.
      Through interlaboratory comparison and consistent intralaboratory emphasis on
      specimen adequacy, greater uniformity of adequacy assessment can be achieved, and
      adequacy evaluation can achieve its promise of improving the quality of cervical
      cytopathology.

PMID- 8261845
TI  - Cytomorphology of familial hemophagocytic syndrome.
AB  - Familial hemophagocytic syndrome (FHS) is a rare, fatal disorder of childhood
      demonstrating failure to thrive, fever, hepatosplenomegaly (HSM), recurrent
      infections, pancytopenia, and histologically, the infiltration of
      reticuloendothelial organs by benign-appearing histiocytes demonstrating
      hemophagocytosis. We report two fatal cases of FHS including a 3 year-old female
      who underwent fine-needle aspiration (FNA) biopsy of the liver in the initial
      workup of the disease (case 1) and an 8 month-old boy with ascites and HSM having
      peritoneal fluid cytology submitted as the first specimen for morphologic
      examination (case 2). In case 1, the FNA cytologic findings included benign
      hepatocytes and scattered mature and reactive lymphocytes and histiocytes. The
      histiocytes demonstrated fine to coarse cytoplasmic vacuoles and
      erythrophagocytosis. The diagnosis was confirmed at autopsy which revealed
      extensive lymphohistiocytic infiltrates in various organs including the central
      nervous system. In case 2, the peritoneal fluid cytology specimen contained
      numerous atypical and degenerating mononuclear lymphoreticular cells which were
      dispersed as a single cell suspension admixed with infrequent mesothelial
      elements; hemophagocytosis was not appreciated. Subsequent liver biopsy revealed
      portal tracts and sinusoids infiltrated by benign but atypical histiocytes with
      hemophagocytosis. Bone marrow examination and then autopsy confirmed the
      diagnosis of FHS. A panel of immunocytochemical studies was performed in the
      first case which was an aid in confirming the diagnosis of FHS and
      ultrastructural examination of the second case revealed well-developed
      erythrophagocytosis. Both patients had siblings who died of FHS. Although not
      diagnostic, cytomorphology may suggest FHS.

PMID- 8261846
TI  - Neural network processing can provide means to catch errors that slip through
      human screening of pap smears.
AB  - The problem of the false-negative smear deserves the attention of the cytologic
      community. We found that by using the PAPNET system, equipped with neural network
      programming, cancer cells can be detected in repeatedly misdiagnosed Pap smears.
      The correct diagnosis of these false-negative smears depended on the skills of
      the diagnostician to recognize the cells on one or more of the 128 tiles of the
      video display as abnormal, and to make the proper decision when to turn to light
      microscopy. In 8 of the 10 tested false-negative smears, the cancer cells were
      found exclusively in epithelial fragments; in two cases there were no more than
      five abnormal cells in the smear (which were detected by PAPNET). This study gave
      us insight into the nature of the false-negative problem and showed us that the
      application of neural network processing can provide means to catch errors that
      slip through human screening of Pap smears.

PMID- 8261847
TI  - Preliminary evaluation of Cyto-Rich: an improved automated cytology preparation.
AB  - A new cervical cytology monolayer preparation system called Cyto-Rich was
      evaluated. Using samples from 557 patients, Cyto-Rich monolayers were compared to
      matched conventional smears. After conventional smears were prepared and spray
      fixed, residual exfoliated cells were transferred to preservative fluid. The cell
      suspensions were gently disaggregated and the epithelial component enriched with
      gradient centrifugal sedimentation. The batched samples were then placed on the
      Cyto-Rich work station where slides are automatically prepared and stained. The
      results demonstrate that Cyto-Rich prepared monolayers are vastly superior to the
      conventional smears for cell presentation. While the study showed 99% overall
      concordance. Cyto-Rich improved the detection of low-grade cervical
      intraepithelial lesions.

PMID- 8261848
TI  - Reactive change and atypical squamous cells of undetermined significance in
      Papanicolaou smears: a cytohistologic correlation.
AB  - The purposes of this study were to delineate morphologic criteria for the terms
      reactive/reparative change (RC) and atypical squamous cells of undetermined
      significance (ASCUS), which were proposed by the Bethesda System, and to evaluate
      the impact of the new terminology on patient management. Using criteria defined
      in this article, 88 cervical smears originally reported as "atypia" were
      reclassified as RC (57) and ASCUS (31). Correlation with the colposcopically
      directed biopsies was as follows: 3/57 RC showed condyloma and 19/31 ASCUS had
      squamous lesions (14 condyloma, four mild, and one moderate dysplasia). The
      remainder of the cases had either cervicitis or no significant abnormality
      histologically. Using the proposed criteria, 61.3% of ASCUS correlated with
      positive biopsies, compared to 5.2% of the RC cases. Our results indicate that
      patients with smears showing RC are significantly less likely to have a squamous
      lesion as compared to those showing ASCUS, and therefore may be managed more
      conservatively.

PMID- 8261849
TI  - Helicobacter pylori in gastroduodenal diseases: rapid identification by
      endoscopic brush cytology.
AB  - Previous reports showed Helicobacter pylori (H. pylori) in type B gastritis
      affected stomachs. This study was carried out to compare H. pylori staining
      effectiveness on biopsy to brush cytology. Tissue and brush parallel samples of
      gastric mucosa with abnormal or normal appearances were examined: 57.6% H. pylori
      positive pieces from the antrum and 19.2% from the body were found, versus 65.3%
      and 25% H. pylori-positive brush smears, respectively. H. pylori resembling
      organisms were mainly related to chronic and acute antral inflammations and were
      often associated with higher amounts of round-shaped cocco-bacteria. In addition,
      H. pylori direct stain on brushing is proposed as the most rapid and reliable
      method for the routine diagnosis of Helicobacter pylori infection, in both ulcer
      or nonulcer gastritis.

PMID- 8261850
TI  - Spindle cell lipoma of the breast: a case report and literature review.
AB  - Fine-needle aspiration cytology (FNA) was performed on a breast lump in a 66-year
      old female, clinically thought to be a carcinoma. The cytological findings were
      reported as suspicious of malignancy. Subsequent histological examination showed
      a tumour macroscopically and microscopically identical with six other cases
      previously described as benign spindle cell tumours of the breast. This report
      highlights yet another diagnostic pitfall in FNA cytology of the breast. The
      presence of floret cells in this case has not been previously reported but
      supports the concept that this lesion is the same as a spindle cell lipoma, from
      which it is virtually indistinguishable on light microscopy. The lesion affects
      both male and female breast, is predominantly single but may be multiple, and
      follows a benign course. Local excision is curative.

PMID- 8261851
TI  - Primary mucoepidermoid carcinoma of the thyroid: diagnosis by fine-needle
      aspiration biopsy.
AB  - Fine-needle aspiration biopsy (FNAB) has been recognized as a safe and reliable
      procedure in the evaluation of thyroid nodules. We herein report a case of a low
      grade mucoepidermoid carcinoma of the thyroid that was diagnosed with this
      technique. Examination of an intra-operative FNAB showed cohesive clusters of
      polygonal squamoid cells with distinct cellular borders, uniform round nuclei,
      distinct nucleoli, and homogeneous amphophilic to cyanophilic cytoplasm. Focal
      keratin "pearl" formation was apparent, along with extracellular, lightly
      basophilic mucin deposits mantled by squamoid cells. These cytologic features are
      characteristic of low-grade mucoepidermoid carcinoma, as seen in other anatomic
      sites. This impression was confirmed by examination of paraffin sections.
      Previous reports have indicated that mucoepidermoid thyroid carcinoma is an
      indolent, locally recurring lesion. However, in spite of low-grade histology in
      our case, the neoplasm presented with distant metastases to bones, pleura, and
      lung.

PMID- 8261852
TI  - Histiocytic necrotizing lymphadenitis (Kikuchi's disease): cytologic diagnosis by
      fine-needle biopsy.
AB  - A cytologic diagnosis of histiocytic necrotizing lymphadenitis (Kikuchi's
      lymphadenitis) was made in a 14-yr-old female with cervical lymphadenopathy,
      fever, neutropenia, and hepatosplenomegaly. A predominance of reticulum cells,
      foamy macrophages, and karyorrhectic debris are clues to the diagnosis in the
      fine-needle biopsy smears. Subsequent histology confirmed the diagnosis of
      Kikuchi's lymphadenitis. The differential diagnoses are discussed including
      malignant lymphoma, which was excluded by morphology as well as flow cytometry
      and polymerase chain reaction (PCR) studies.

PMID- 8261853
TI  - Fine-needle aspiration of histiocytic necrotizing lymphadenitis (Kikuchi's
      disease).
AB  - Fine-needle aspiration (FNA) of the lymph node was done in five patients with
      histiocytic necrotizing lymphadenitis (Kikuchi's disease). In four patients, the
      aspirates were found to have many small and large atypical lymphocytes, some
      reactive, phagocytic histiocytes, and intense extracellular debris. Neutrophils,
      plasma cells, or multinucleated giant cells were not seen. These cytologic
      findings were considered diagnostic for Kikuchi's disease. In one patient, the
      aspirate did not show significant histiocytosis or tissue necrosis and was
      considered nondiagnostic. In patients with both typical clinical features and
      characteristic cytologic findings in the lymph node aspirates, FNA of the lymph
      node alone will suffice for diagnosis. In those patients with typical clinical
      features but nondiagnostic findings in the FNA aspirates, the diagnosis of
      Kikuchi's disease may have to be established either on repeated nodal FNA or on
      lymph node biopsy.

PMID- 8261854
TI  - Fine-needle aspiration cytology of idiopathic pancreatic islet cell adenosis.
AB  - A 68-yr-old woman was hospitalized because of abdominal pain, an enlarged
      pancreatic head by CT, and a questionable 4-cm mass in the liver. Fine-needle
      aspiration (FNA) of the pancreatic head disclosed a highly cellular specimen
      consisting of clusters of cytologically bland, monotonous, small nuclei and
      variable but generally sparse cytoplasm. Because of the differentiated
      monomorphic character of the cell clusters, the postaspiration differential
      cytopathologic diagnosis included islet cell tumor, acinic cell tumor, carcinoid,
      lymphoma, and well differentiated ductal adenocarcinoma. Pancreaticoduodenectomy
      and hepatic biopsy yielded a grossly normal pancreas and a cirrhotic liver.
      Histologic examination of the pancreas revealed a spotty but extensive spectrum
      of islet changes ranging from normal to bland hyperplasia, nesidioblastosis,
      microadenosis, and neuroendocrine microadenomas, all appearing in a light and
      electron microscopic context of an otherwise normal pancreas. This case
      highlights the differential diagnostic ambiguities presented by a continuum of
      pancreatic islet cell proliferations, especially among patients in whom there are
      no known predisposing factors for such diffuse preneoplastic or neoplastic
      changes.

PMID- 8261855
TI  - Fine-needle aspiration cytology of juvenile papillomatosis of breast: a case
      report.
AB  - The cytologic findings of juvenile papillomatosis (JP) have been rarely
      described. The clinical and cytologic findings were suggestive of a fibroadenoma,
      but due to the presence of 2 cc of clear fluid during the aspiration, fibrocystic
      change was in the differential diagnosis. Operation and subsequent examination of
      the mass identified a case of JP (so-called Swiss cheese disease of the breast).
      Because JP is a marker for breast carcinoma for the patients' families, and the
      patients may themselves be at increase risk for malignancy, it is important that
      this entity be considered in the differential diagnosis. The observations in this
      case indicate that it is difficult to diagnose JP only by cytology, but the
      combination of clinical findings--a well-circumscribed mass in a young patient
      with cystic fluid, but with a residual mass after aspiration due to the
      multicystic nature of JP--with the cytologic findings--sheets of hyperplatic
      breast epithelium with areas resembling fibroadenoma, macrophages, and apocrine
      cells--that appear to be sufficiently characteristic to suggest the diagnosis of
      JP.

PMID- 8261857
TI  - Fine-needle aspiration of intra-abdominal desmoplastic small cell tumor.
AB  - The cytologic features of four cases of histologically confirmed intra-abdominal
      desmoplastic small cell tumor (DSCT) that occurred in males between 18-27 yr of
      age are presented. Smears showed small cells with scant cytoplasm which were
      primarily arranged in loosely cohesive clusters. Nuclei were oval to round with
      evenly distributed, finely granular chromatin and inconspicuous nucleoli. As is
      typical of DSCT, the cells strongly expressed keratin and desmin in all cases. In
      the one case studied by electron microscopy, it was demonstrated that the cells
      were joined by small junctions and contained paranuclear aggregates of
      intermediate filaments. The absence of the characteristic desmoplastic stroma in
      DSCT aspirates and the nonspecific cytologic features of this small round-cell
      tumor (SRCT) made cytologic interpretation difficult. Cytopathologists should be
      aware of this entity so that DSCT is included in the differential diagnosis of
      SRCTs that occur in intra-abdominal sites. A panel of markers that includes
      keratin and desmin should be used to assist in the identification of DSCT.

PMID- 8261856
TI  - Needle aspiration cytology, immunocytochemistry, and electron microscopic study
      in a case of carcinoid of the male breast.
AB  - The diagnosis of a primary carcinoid of breast in a 68-yr-old male was initially
      made from a sample of needle aspirate. The cytodiagnosis was supported by
      histochemical and immunocytochemical studies which showed positivity for
      argyrophilic granules by Grimelius stain and positive staining for chromogranin.
      A subsequent cell block of the aspirate and biopsy of the tumour confirmed the
      cytodiagnosis. Electron microscopic study of the material further demonstrated
      the presence of neurosecretory granules in the malignant cells. Mastectomy with
      axillary node dissection was performed and showed no residual or metastatic
      tumour. No primary tumour was found elsewhere. This case illustrates the
      importance of needle aspiration cytology in the diagnosis of carcinoid tumour
      which is very rare in the male breast.

PMID- 8261858
TI  - Preoperative cytodiagnosis of primitive carcinoid tumor of the Wirsung duct: a
      case report with immunocytochemical study.
AB  - A case of primitive carcinoid tumor of the Wirsung duct detected by fiberoptic
      guided brushing cytology is reported. The authors describe the main
      cytomorphologic characteristics and underline the role of immunocytochemistry in
      helping to reach a reliable preoperative diagnosis.

PMID- 8261859
TI  - Appearance of goblet cells in atrophic vaginal smears.

PMID- 8261860
TI  - [Preliminary report on the results of nutrition prevention trials of cancer and
      other common diseases among residents in Linxian, China].
AB  - To examine whether vitamin/mineral supplementation may lower mortality and
      incidence from human cancer and mortality from other diseases as well as to
      provide the scientific basis and feasible approach for human cancer prevention
      and control, between 1982-1991 scientists from China and USA conducted two
      randomized, double-blind, and placebo-controlled nutrition intervention trials in
      Linxian, China, where the esophageal/gastric cardia cancer mortality rates are
      among the highest in the world and there is suspicion that the population's
      chronic deficiencies of multiple nutrients are etiologically involved. In the
      first trial, the Dysplasia Trial, 3,318 individuals with a cytologic diagnosis of
      esophageal dysplasia received daily 26 vitamin/mineral supplements or placebos
      for 6 years; The second trial, the General Population Trial, involved 29,584
      individuals and used an one-half replicate of a 2(4) fractional factorial design
      which randomized to 8 groups for testing the effects of daily supplementation of
      4 different vitamin/mineral combinations and placebo for a period of 5 1/4 years.
      Compliance assessed by monthly pill counts and quarterly monitoring of
      biochemical assays indicated that the participant compliance was excellent. As
      endpoints of the trials, incident cancers and deaths were identified through all
      medical facilities in local areas, supplemented by special endoscopy and cytology
      examinations, and confirmed by 3-level review groups. A total of 323 deaths
      occurred during 6 year period among participants in the dysplasia trial, and
      2,127 deaths from the general population trial during 5 1/4 years. Besides, an
      eye examination, which included detailed lens evaluations, was included in the
      extensive re-examination protocol to ascertain whether use of the supplements had
      affected the risk of developing age-related cataracts among participants in the
      two trials. Results from Dysplasia Trial indicated that after 6 years of daily
      supplementation with multiple vitamins and minerals, total mortality among those
      in the active treatment group was slightly (9%) lower than in the placebo group;
      and deaths of esophageal cancer also declined by 17%, as well as a sizeable
      reduction in cerebrovascular disease mortality (near 40%) was seen, though none
      was statistically significant. However, intervention had decreased prevalence of
      eye nuclear cataract (43%) (P < 0.01). The findings from the General Population
      Trial provide support for the hypothesis that intake of specific micronutrients
      may inhibit cancer development. Significant reduction of total mortality (9%),
      cancer mortality (13%), gastric cancer mortality (20%), and mortality of the
      other cancers (19%) occurred among those receiving beta-carotene/vitamin
      E/selenium supplementation (P < 0.05). Patterns of cancer incidence, based on
      1307 cases, generally resembled those for cancer mortality.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8261861
TI  - [In-vitro and in-vivo studies on the antitumor activity of LICC in Km mice].
AB  - In order to investigate a more efficient effector cell than the classical LAK
      cell in tumor immunotherapy, anti-tumor activity of lymphokine-induced cytotoxic
      cell (LICC) was studied. The results showed that LICC had greater cytotoxicity to
      YAC-1, HL60, P815 and H22 tumor cells in vitro than the control spleen cells. In
      vivo, LICC revealed a prominent inhibiting effect on the growth of H22 cells. A
      mixture of LICC and H22 in the ratio of 100: 1 was injected subcutaneously into
      the subaxillary tissue of Km mice (Group 1). Tumor developed in 8% of the
      experimental animals within 10 weeks, while all of the control animals inoculated
      with H22 cells died from tumor in the same period (P < 0.001). In the other
      groups, H22 cells were injected as in group 1, but the LICC cells were
      administered through the tail vein (Group 2) or to the abdominal cavity (Group 3)
      once every week. In group 2, tumor developed in 25% of the experimental mice and
      100% of the control mice (P < 0.001). In group 3, there was no significant
      difference in the frequency of tumor development between the experimental and
      control animals.

PMID- 8261862
TI  - [In vivo studies on PGE2 production by human hepatocellular carcinoma xenografts
      in nude mice].
AB  - The PGE2 concentration of sera and tumor tissues in human hepatocellular
      carcinoma (hHCC) xenografts in nude mice was examined by radio-immuno-assay (RIA)
      and the effect of intraperitoneal administration of exogenous of PGE2 as well as
      indomethacin on tumor growth was studied. The results showed that: (1) Plasma and
      tumor tissue PGE2 levels of hHCC-bearing nude mice were significantly increased
      for 1 or 2 weeks after tumor inoculation. (2) Exogenous administration of
      indomethacin markedly suppressed the elevation of plasma and tissue PGE2 levels
      and prolonged the latent period of tumor growth. (3) Exogenous PGE2 shortened the
      latent period of tumor growth. This study indicates that there is intimate
      relation between PGE2 and hHCC growth.

PMID- 8261863
TI  - [Expression of EGF-R in gastric carcinoma and precancerous lesion].
AB  - The expression of epidermal growth factor receptor (EGF-R) in normal gastric
      mucosa, gastric mucosal dysplasia, early and advanced gastric carcinoma was
      studied with the monoclonal antibody to EGF-R by using immunohistochemical ABC
      method. Normal gastric mucosa was negative for EGF-R, but a relatively high
      positive rate was found in dysplasia. When gastric carcinoma occurred, the
      positive rate decreased. The expression of EGF-R was related to the poor
      differentiation and strong infiltration of gastric carcinoma. The carcinoma with
      the expression of EGF-R was easy to metastasize to lymph nodes. The result
      suggests that EGF-R might play some role in the process of carcinogenesis of
      gastric mucosa, and be used as a useful marker for the assessment of the
      biological behavior of gastric carcinoma.

PMID- 8261864
TI  - [Establishment of a model of human gastric cancer with liver metastasis in nude
      mice].
AB  - An animal model of liver metastasis was established by injection of suspending
      tumor cells into subcapsule of spleen in nude mice. With additional mechanic
      disaggregation, single-tumor cell suspension was prepared by enzymatic
      disaggregation, including trypsin-collagenase disaggregate medium treatment, from
      the subcutaneous MGC 80-3 xeno-transplanted tumor and filtered through filter
      holders with different pore size. To investigate the effect of liver damage by
      carbon tetrachloride (CCL4) on the metastatic potential of MGC 80-3 cells
      injected intrasplenically, the nude mice were divided into 2 groups: Group 1
      received intrasplenic injection of 1.25 x 10(6) MGC 80-3 cells without CCL4
      treatment; Group 2 received intrasplenic injection of equal cells with CCL4
      treatment. The incidence of liver metastasis was 60% in Group 1, but 100% in
      Group 2. The mean numbers of metastatic nodules per liver were 1.80 in Group 1,
      but 4.85 in Group 2. It is obvious that the incidence and nodules of liver
      metastasis were increased in the mice treated with CCL4. This is a useful model
      to study antimetastatic agents and metastatic behaviors.

PMID- 8261865
TI  - [Immunoscintigraphy of human pancreatic cancer an experimental study].
AB  - A monoclonal antibody against human pancreatic carcinoma APCA-1, was developed.
      By immunohistochemical staining, it had pretty good reactivity to carcinoma of
      the pancreas, bile duct and gall bladder. Their positive rates were 94.1%, 80%
      and 75%, respectively. It cross reacted weakly with normal epithelial cells of
      the pancreas, gall bladder and bile duct in relatively low frequency.
      Immunoscintigraphy was performed in nude mice with xenograft of human pancreatic
      cancer using 131I-labeled APCA. Good radio-imaging of the tumor xenograft was
      achieved. The ratio of radioactivity of each gram of tumor tissue to total
      radioactivity reached 5.1%, 6.9% and 6.2% at 72,120 and 168 hr respectively.

PMID- 8261866
TI  - [Comparison of the therapeutic effect of CMxMF and CAMF regimens in the
      management of advanced breast cancer patients].
AB  - From April 1990 to April 1992, a comparative study was carried out in 46 patients
      with advanced breast cancer treated by CMxMF (Cyclophosphamide, mitoxantrone,
      methotrexate, 5-fluorouracil) and CAMF regimens (Cyclophosphamide, adriamycin,
      methotrexate, 5-fluorouracil). Of these 46 patients, 23 treated by CMxMF regimen
      gave a response rate of 87% (20/23) and 23 treated by CAMF regimen gave a
      response rate of 82.6% (19/23) (P > 0.05). Following up to the end of June, 1992,
      21 patients in CMxMF regimen were still alive with a median survival of 16 (6-24)
      months and 20 patients in CAMF regimen with a median survival of 12 (3-24)
      months. The side effects were tolerable in both groups. The authors consider that
      mitoxantrone is as effective as adriamycin in the treatment of advanced breast
      cancer.

PMID- 8261867
TI  - [Effectiveness of treatment with transfer of autologous or allogenic LAK cells
      combined with rIL-2 in 121 patients with malignant pleural effusion].
AB  - Lymphocytes isolated from malignant pleural effusions of patients with advanced
      lung cancer or from allogenic peripheral blood of healthy donors were induced to
      become LAK cells after in vitro culture with rIL-2. One hundred and twenty-one
      patients with malignant effusions were treated by intrapleural administration of
      autologous or allogenic LAK cells combined with rIL-2. The effusions disappeared
      in 71 (58.6%) patients and significantly decreased in 45 (36.2%) patients. Five
      patients did not respond to the treatment. Tumor cells in pleural effusions
      disappeared or significantly decreased and lymphocytes significantly increased in
      all responders. Except for transient chill and/or fever in 102 patients, no
      serious side effect was found. The results indicate that transfer of autologous
      or allogenic LAK cells combined with rIL-2 in the treatment of patients with
      malignant pleural effusions due to advanced lung cancer is feasible effective,
      and safe.

PMID- 8261868
TI  - [Results of surgical treatment of stage I non-small cell lung cancer].
AB  - Results of surgical treatment of 152 cases of stage I non-small cell lung cancer
      from 1985 to 1989 are reported. The 1, 3, 5-year survival rates were 92.1%,
      74.5%, 64.6%, respectively. Among 152 cases, there were 100 squamous carcinoma,
      44 adenomatous carcinoma and 8 squamous and adenomatous mixtures. There were 50
      cases of T1 N0 M0 and 102 of T2 N0 M0 according to TNM staging. Of the 152 cases,
      46 were discovered by regular physical check-up without symptoms and 106 by
      patient complaints. 130 cases underwent lobectomy, 14 cases pneumonectomy, and 8
      cases sectional or wedge cut. Comparison of the 5-year survival rate after the
      operation was: T1 N0 M0 > T2 N0 M0; squamous > adenomatous; lobectomy >
      pneumonectomy (P > 0.005); cases detected by regular check-up > those with
      symptoms (P < 0.005). The 5-year survival rate of stage I lung cancer was 64.6%.
      There is no difference from the result of those in 1960s and 1970s. More
      effective combination therapy is needed to increase the survival rate.

PMID- 8261869
TI  - [Local excision of cancer of the rectum].
AB  - Conservative treatment of 35 patients with rectal cancer by local excision is
      reported. Limited surgery of rectal cancer can be a part of treatment of this
      tumor. Selection of the patient for limited surgical procedure should be strictly
      in accordance with the following criteria: tumor diameter less than 3 cm,
      clinical staging I and II, histologically well differentiated type, tumor
      invasion no deeper than the submucosa and patients with severe cardiopulmonary
      diseases who could not withstand radical surgery. A transanal local excision is
      the most straightforward approach. Local excision was by per anal full-thickness
      disc excision and trans-sphincteric disc excision. Prognosis and further
      treatment were based on the histopathologic results of operative specimen. The
      overall 5-year survival rate was 71.4% (18/21) and 10-year survival rate 33%
      (7/21).

PMID- 8261870
TI  - [High dose cisplatin combination chemotherapy for advanced breast cancer--a
      report on 50 cases].
AB  - Fifty patients with advanced breast cancer were treated by high dose cisplatin
      (DDP) combination chemotherapy during the period of August 1984 to June 1991. All
      of them had measurable disease. Among the fifty patients, 24 had previously
      received chemotherapy. DDP was given at a dose of 50-128 mg/m2 intravenously
      every 3 weeks. The regimen was PCMF (DDP + CTX + MTX + 5FU), PA (DDP+ADM) +/-
      other agents or PF (DDP + 5FU) +/- other agents. The overall response rate was
      76% (38/50) with a CR rate of 20% (10/50). The median response duration and
      median survival time were 5.5 months and 15 months, respectively. Best response
      was obtained in soft tissue metastasis (83.3%, 40/48), and in lung metastasis
      (79.3%, 23/29). The response rate was lower in liver metastasis (40%, 2/5) and
      lowest in bone metastasis (0/9). Marked gastrointestinal reaction was observed in
      most patients (84%). These results indicate that high dose cisplatin combination
      chemotherapy is an effective regimen for advanced breast cancer.

PMID- 8261871
TI  - [Preliminary experience with colposcopic diagnosis of cervical adenocarcinoma].
AB  - Colposcopic technique has become a major method in the diagnosis of cervical
      cancer. Sixteen patients of adenocarcinoma of the cervix were examined by
      colposcopy from 1984.2 to 1991.6. Transformation-zone-like and papillary finding
      were common colposcopical appearances of adenocarcinoma of the cervix. The common
      vascular patterns in 16 cases were root-like vessels and waste-thread-like
      vessel. Among the 16 cases, cytologic positive rate was only 25% (3/12), while
      the accordance rate between colposcopic examination and pathology was 84.6%
      (11/13). The result suggests that colposcopic examination is superior to the
      cytology in the diagnosis of cervical adenocarcinoma. Based on the above results
      and the data of literature, we consider that there are obvious differences of
      colposcopic findings between adenocarcinoma and squamous cell carcinoma of the
      cervix which may be useful in the early diagnosis of the cervical adenocarcinoma.

PMID- 8261872
TI  - [Rectosigmoid carcinoma--role of postoperative follow-up pelvic CT].
AB  - Pelvic CT scans of 102 patients who underwent resection of rectosigmoid carcinoma
      are reviewed. Sixty one patients had abdominoperineal resection and 41 had
      abdominal resection and colostomy. Recurrent tumors developed in 31 patients
      (30.4%). The interval between surgery and tumor relapse ranged from 3 months to
      108 months (median, 14 months). CT findings indicative of tumor recurrence
      included an eccentric, round or irregular presacral soft-tissue mass, 2-20 cm
      (16), marked enhancement after i.v. contrast administration (15), invasion of
      surrounding muscle and/or bone (4), six patients had perineal recurrent tumor
      which was eccentrically located and irregular in shape. Fifteen patients
      developed recurrent tumor after abdominal resection and colostomy. There were
      anastomotic recurrence (15), pari-anastomotic mass (5), regional metastatic
      adenopathy (6), ranging from 0.3 to 1.2 cm. Routine follow-up CT scan after
      rectosigmoid carcinoma resection is useful in depicting early recurrence and
      survival could be improved after salvage operation. Appropriate scanning
      techniques including air inflation of the remaining rectum and colon, i.v.
      contrast administration for enhancement of tumor mass and blood vessels are
      emphasized for improving the quality of CT images in order to differentiate
      recurrence or postoperative change, adenopathy or blood vessels. Enhancement of
      tumor mass and blood vessels are emphasized for improving the quality of CT
      images in order to differentiate recurrence or postoperative change, adenopathy
      or blood vessels.

PMID- 8261873
TI  - [Clinical study on super-long-term survival over 15 years of postoperative
      patients with lung cancer].
AB  - A total of 1478 patients with lung cancer were operated upon at the Shanghai
      Chest Hospital from 1958 to 1973. The resectability was 88.6%. Up to May 1989,
      128 patients with a super-long-term survival, from 15 to 31 years (md = 18.8
      years) after resection, had complete data for analysis. Seventy one (55.5%)
      patients are still alive. The 15-year survival rate was 8.7%. After 15 years of
      postoperative survival, only the death rate of smoking group (BI = 538) was
      significantly higher than that of non-smoking group in eleven statistic items
      (chi 2 = 4.45, P < 0.05). This suggests that smoking exerts a negative influence
      on super-long-term survival by reducing the immune function and inducing senile
      chronic pulmonary-cardiovascular diseases in the host. The importance of radical
      resection and healthy psychological status of the host for super-long-term
      survival is discussed.

PMID- 8261874
TI  - [Evaluation of mass screening for colorectal cancer with 'sequential fecal occult
      blood test' in an asymptomatic population. Multicenter GI Research Group of
      Beijing Area of PLA].
AB  - In order to search for a reasonable screening method for colorectal cancer in
      accordance with the situations in China, we designed the sequential fecal occult
      blood test' (CFOBTS-->IFOBT-->colonoscopy) and compared with chemical fecal
      occult blood test (CFOBT) and immuno-fecal occult blood test (IFOBT). On the
      basis of our findings, SFOBT is not only sensitive, easy to perform but also
      economical as compared with CFOBT & IFOBT. By using the program of SFOBT, we
      carried out a mass screening of an asymptomatic population of 102,800 people,
      covering five provinces in northern China. The results are as follows: (1) The
      incidence of colorectal cancer in northern China was about 24.31/10(5); (2) 52%
      of colorectal cancer cases detected through the screening were classified as
      Dukes stages A or B, whereas only 36.83% are those clinically diagnosed (P <
      0.05); (3) The incidence of colorectal cancer increased with age, the high-risk
      age group peak at 60-69 years; (4) 84% of cancer & 62.23% of adenomas were
      detected in sigmoid colon or rectum; (5) The incidence of colon tumour was
      significantly increased in subjects with family history of colon tumour as
      compared with those without; (6) Diet habits of different nationalities may not
      be related to the morbidity of colorectal cancer. In conclusion, mass screening
      for early detection of colorectal cancer following SFOBT program is suitable for
      the situations in China.

PMID- 8261875
TI  - Methadone dose and treatment outcome.
AB  - Consensus on the optimal dosing of methadone in the treatment of opioid
      dependence has not yet been achieved, with some programs committed to low dose
      regimens. This paper presents outcome results for 95 opioid abusers who remained
      in treatment through a stable dosing period in a double-blind fixed dose clinical
      trial comparing the relative efficacies of 50 (n = 44) and 20 mg (n = 34) of
      methadone to methadone-free treatment (n = 17). All patients showed improvements
      over time on measures of psychosocial functioning and psychological symptoms,
      emphasizing the important role of non-pharmacologic factors in methadone
      treatment. Furthermore, orderly dose effect relationships were seen, with
      patients receiving 50 mg of methadone having significantly lower rates of opioid
      positive urines (36% vs. 60-73%), and self-reporting a lower frequency of heroin
      use (3 days vs. 11-12 days per month). These results illustrate the dose-related
      efficacy of methadone in decreasing illicit opioid use and improving drug-related
      behavior.

PMID- 8261876
TI  - The effects of dose and access restrictions on the periodicity of cocaine self
      administration in the rat.
AB  - Cocaine self-administration in rats was tested under various dose and frequency
      of access restrictions. In the continuous access condition, groups of rats were
      given continuous, unlimited access to one of three doses of cocaine (1.5, 0.5,
      and 0.2 mg/kg/infusion) for a duration of 10 days. In the discrete trials
      condition, a group of rats were given the opportunity to self-administer a single
      cocaine infusion (1.5 mg/kg) within a discrete, 10 min access trial. The rats
      received a continuous series of these trials for a duration of 7-10 days at one
      of three frequencies (1, 2 or 4 trials/h). Results suggest that when access is
      restricted to four access trials/h, or to a median dose range (0.5 mg/kg per
      infusion), rats will self-administer cocaine in a cyclical manner over extended,
      infradian periodicities without developing outward signs of ill health. This
      contrasts with previous studies where extended, unlimited access schedules have
      resulted in toxicity and overdose. It is suggested that dose and frequency of
      access restrictions may be employed in order to develop new animal models of
      cocaine self-administration which examine the factors underlying the reinitiation
      of extended periods of cocaine intake. Such models may be useful in testing
      interventions with the potential to disrupt cyclical patterns of cocaine self
      administration.

PMID- 8261877
TI  - Early smoking initiation and nicotine dependence in a cohort of young adults.
AB  - We examined the extent to which nicotine dependence and daily smoking might vary
      by age at first cigarette. The potential confounding effects of sex, race and
      history of childhood behaviour problems were examined as well. A sample of 1200
      was randomly selected from the subset of 21-30-year-old members of a large HMO in
      the Detroit SMSA; 1007 (84%) agreed to participate. Personal interviews were
      conducted in respondents' homes, using the NIMH-DIS to elicit information on DSM
      III-R diagnoses, including nicotine dependence. Controlling for sex and race,
      persons who smoked their first cigarette at 14 to 16 years of age were 1.6 times
      more likely to become dependent than those who initiated smoking at an older age
      (P = 0.03). The association was unchanged when history of childhood behaviour
      problems was also controlled. Smoking initiation before age 14 was not associated
      with increased probability of dependence. Persons who initiated smoking before
      age 14 had a longer lag time to daily smoking and a lower likelihood of
      progressing to daily smoking, compared to persons who initiated smoking later on.
      The findings suggest that, among persons who have ever smoked, there might be two
      distinct groups in whom the chances of developing dependence are considerably
      reduced. The first comprises persons who delayed first use until age 17. The
      second comprises persons who smoked their first cigarette before age 14, a group
      in whom the progression to daily smoking might be markedly slower than in persons
      who initiated smoking when they were older.

PMID- 8261878
TI  - Alcohol use and abuse in the frail, homebound elderly: a clinical analysis of 103
      persons.
AB  - We studied alcohol use and abuse in 103 frail, homebound elderly individuals
      cared for in a long-term home health care program from July 1991 to February
      1992. Their average age was 80.63 years. Eighty-four percent were abstinent at
      the time of the study, including 25 (25%) past heavy drinkers. Two persons were
      current heavy drinkers and 14 continued to drink socially. Previous alcohol use
      or abuse was associated with a history of smoking, cardiovascular morbidity,
      social isolation, and anxiety or agitation. Current social drinking was
      associated with sedative-hypnotic use as well as smoking. Twenty-three of 25 past
      heavy drinkers remained sober on our programs without the use of formal alcohol
      treatment. Abstinence is known to increase with age, appears to be fostered by
      the homebound setting, is feasible for homebound elderly persons and is often
      accepted.

PMID- 8261879
TI  - Serum neopterin levels in alcoholic liver disease.
AB  - Serum neopterin levels have been determined by RIA in 105 patients affected by
      chronic alcoholic liver disease, 68 of them cirrhotics, and in 12 controls. Serum
      Neopterin was significantly higher in patients than in controls, correlated with
      Pughs' score and Child's classification, and also with serum laminin and type III
      collagen N-terminal propeptide, and with histomorphometrically determined liver
      fibrosis. Serum neopterin levels were higher in patients who died than in
      survivors, serum neopterin levels over 19.15 nmol/l being associated with higher
      mortality rates.

PMID- 8261880
TI  - Baclofen administration for the treatment of affective disorders in alcoholic
      patients.
AB  - Ninety alcoholic patients with the secondary affective disorders (anxiety,
      depression) were divided into four groups. Patients in the first group received
      GABAB receptor ligands (baclofen), those in the second group, diazepam, those in
      the third group, amitriptyline and those in the fourth group, placebo. The
      results of clinical, psychological (tests of Spielberger, Zung and MMPI), and
      electrophysiological (superslow omega-potential) investigations showed that
      baclofen is an effective drug for affective disturbances in alcoholic patients,
      with efficacy superior to placebo and equal to diazepam and amitriptyline. At the
      same time baclofen does not have the side-effects and complications of the
      latter. Significant changes in platelet MAOB activity and the dopamine, serotonin
      and GABA concentrations in blood after treatment were not found in the four
      patient groups. The peripheral matabolism of GABA and monoamines do not seem to
      be related to the development of secondary affective disorders in alcoholic
      patients. This investigation encourages the search for drugs acting on the
      affective psychopathology of GABAB receptor ligands.

PMID- 8261881
TI  - Behavioral economics of drug self-administration: an introduction.
AB  - Behavioral economics provides a set of concepts for the analysis of factors that
      control the allocation of behavioral resources among available reinforcers. Terms
      from micro-economics describe new phenomena previously ignored within the
      traditional context of behavior analysis. This article reviews these concepts as
      an introduction to the three papers that follow. The primary dependent measure
      within the behavioral economic framework is the level of consumption of available
      commodities as determined by the level and distribution of instrumental
      responding. The demand curve provides a quantitative metric for analyzing
      consumption under the constraint of unit price. When the reinforcer is a drug,
      the demand curve can be a useful tool for analyzing the level of motivation to
      consume the drug, its abuse liability, and for evaluating interventions, such as
      alternative reinforcers or medications, to reduce the motivation to consume the
      drug and instrumental responding to obtain it. Behavioral economics also provides
      a framework for formulating, testing, and refining drug abuse policy through a
      series of empirical steps that maximize effectiveness and minimize undesirable
      social consequences.

PMID- 8261882
TI  - Behavioral economics: a novel experimental approach to the study of drug
      dependence.
AB  - Drug abuse and dependence are among the most important problems facing society
      today. Understanding the determinants of drug abuse has been advanced by a
      considerable quantity of research on environmental and pharmacological factors
      that control drug taking in a variety of settings and species. Behavioral
      economics, which is the application of economic principles to the behavior of the
      individual, may have the potential to integrate a number of these empirical
      observations in a novel quantitative framework. In this paper the utility of
      behavioral economics for the study of drug dependence is reviewed. Specifically,
      we reviewed (i) the parsimony behavioral economics affords via the integration of
      variables, (ii) a ubiquitous behavioral process it has identified, (iii) the
      precise quantification of that behavioral process and its predictive utility,
      (iv) a novel independent variable suggested by behavioral economics, and (v) the
      utility of behavioral economic notions for the process of medication development.
      We conclude that behavioral economics provides a novel conceptual framework that
      has utility for the study of drug dependence.

PMID- 8261883
TI  - Behavioral economics and drug choice: effects of unit price on cocaine self
      administration by monkeys.
AB  - The application of microeconomic theory to the experimental analysis of behavior
      has been termed behavioral economics. There has been an increasing interest in
      applying the concepts of behavioral economics to the study of drug self
      administration. In a previously published experiment (Nader and Woolverton,
      1992), rhesus monkeys (N = 3) were trained in a discrete-trials choice procedure
      and allowed to choose between intravenous injections of cocaine (0.03-1.0
      mg/kg/injection) and food presentation (1 or 4 pellets; 1 g/pellet) during daily
      7-h experimental sessions. When cocaine or food was available under a fixed-ratio
      (FR) 30 schedule, cocaine intake increased in a dose-related manner for all
      monkeys. When the response requirement (FR) for cocaine was differentially
      increased by doubling or quadrupling, the frequency of cocaine choice decreased,
      shifting the cocaine dose-response function to the right. The present paper is a
      reanalysis of data from that experiment. Several mathematical models,
      differentially incorporating the effects of FR, dose and number of food pellets,
      were compared. When cocaine consumption was analyzed using a multiple linear
      regression analysis with FR, dose and number of pellets as separate main effects
      (model I), the R2 was 0.82. When FR and dose were combined into one factor, unit
      price (UP, responses/mg/kg), and cocaine consumption was analyzed as a linear
      function of UP (model IIA), the R2 was 0.54. When cocaine consumption was
      analyzed as a curvilinear, negatively accelerated function of UP (model IIB), the
      R2 was 0.53. The difference between models I and IIA was statistically
      significant while models IIA and IIB were not different.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8261884
TI  - The economic context of drug and non-drug reinforcers affects acquisition and
      maintenance of drug-reinforced behavior and withdrawal effects.
AB  - The focus of this review is to examine the effect of non-drug alternative
      reinforcers on drug-reinforced behavior. An increasing number of animal
      laboratory as well as human clinical studies have demonstrated the effectiveness
      of non-drug reinforcers in reducing steady-state levels of drug self
      administration. One goal of this review was to determine what behavioral economic
      conditions are optimal for reducing drug-reinforced behavior. Variables such as
      price of the drug and non-drug reinforcer have been manipulated by changing fixed
      ratio (FR) value of these commodities. Income has been changed by limiting the
      amount of access to the commodities or by changing session length. Substitution
      was evaluated by determining whether decreased demand for a drug (due to
      increased price) was related to increased demand for a non-drug reinforcer. A
      second goal of this review was to investigate transition states in the drug
      addiction process with respect to the role of alternative non-drug reinforcers.
      Animal models of acquisition and withdrawal were examined to identify behavioral
      economic conditions under which acquisition may be prevented or withdrawal
      effects (and potential for relapse) may be alleviated.

PMID- 8261885
TI  - Subjective reports of withdrawal among cocaine users: recommendations for DSM-IV.
AB  - The proposed DSM-IV criteria for substance use disorders have included, as an
      option, a subtyping for physiologic dependence, characterized by either tolerance
      or withdrawal. Even if this option is not chosen at this stage of system
      revision, this weighting scheme justifies wider surveillance of these symptoms,
      especially for the more newly described cocaine dependence disorder. Wider
      surveillance of withdrawal is possible with the CIDI Substance Abuse Module
      (SAM), a WHO/ADAMHA diagnostic interview which covers criteria of substance use
      disorders according to the DSM-III, III-R, ICD-10 and proposed DSM-IV systems. To
      aid in this effort, we used the SAM, which includes a master list of all symptoms
      (n = 16) in the DSM manuals related to withdrawal from any substance to assess
      withdrawal symptoms from all substances. In this study, we hypothesized that the
      persons who used opiates with cocaine might misattribute their symptoms to
      cocaine; thus, we compared the responses of persons who used cocaine and opiates
      (opiate users) with the responses of persons who used cocaine without opiates
      (non-opiate users). Data from two St. Louis studies were combined for these
      analyses, users not in treatment or newly enrolled to drug-free or methadone
      treatment from a NIDA demonstration project and users selected for the St. Louis
      DSM-IV Field Trial. Of the 196 persons included from the field trial, 80%
      reported lifetime cocaine use compared with 91% of the 412 persons from the
      demonstration project. The symptoms mentioned in the diagnostic manuals were
      among the most frequently endorsed by both cocaine use groups.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8261886
TI  - Clinical trials using ascorbic acid aerosol to aid smoking cessation.
AB  - Sensory aspects of cigarette smoke are important for providing smoking
      satisfaction. In previous studies, we have found that substitution of the sensory
      cues of smoking with a citric acid aerosol significantly reduces craving for
      cigarettes and enhances smoking reduction and cessation with people trying to
      quit smoking cigarettes. In the current study, we conducted two clinical smoking
      cessation trials using an ascorbic acid aerosol as a sensory substitute. The
      cigarette substitute consisted of a cigarette-sized tube which delivered a fine
      aerosol of ascorbic acid (approx. 1 mg/puff, up to a maximum of 300 mg/day).
      Study 1 examined the overall effectiveness of the ascorbic acid smoking
      substitute device. One group of subjects which used the device and received
      clinical counseling was compared with another group which received only clinical
      counseling. The group using the device showed significantly greater abstinence
      rates at 3 weeks post-cessation. After the subjects stopped using the device, no
      difference in abstinence was detected. Study 2 was conducted to focus
      specifically on the role of tracheobronchial sensations in relieving craving for
      cigarettes. Two closely matched ascorbic acid delivery systems were compared. One
      device delivered fine particles of ascorbic acid that were targeted to reach the
      trachea, while the other delivered coarser particles of ascorbic acid that were
      not expected to reach the trachea or lower airways. An initial enhancement in
      smoking reduction was found for subjects using the fine particle device relative
      to those using the coarse particle device. However, by the end of treatment (5
      weeks) both groups showed similar degrees of smoking reduction. For those who
      were abstinent from smoking at the end of treatment, craving for cigarettes and
      negative mood were both significantly lower for those using the fine particle
      device. Also, hunger for food was significantly lower in the fine particle device
      group. These results suggest that ascorbic acid delivered from a cigarette
      substitute may be effective in reducing smoking and promoting smoking abstinence.

PMID- 8261887
TI  - Effects of cocaine self-administration on ethanol, food and water intake in the
      rat.
AB  - Because cocaine and ethanol are frequently abused in combination, the present
      study was performed to assess the behavioral consequences of concurrent access to
      both of these drugs. Rats trained to respond for food under a fixed-ratio 40 (FR
      40) schedule of reinforcement during four, 30-min periods each day (every 6 h)
      were given free access to a 5% (w/v) ethanol solution and to water. Once a stable
      baseline of food, ethanol and water intake was established, intravenous cocaine
      was made available under a fixed-ratio 1 (FR1) schedule. After cocaine self
      administration had been established for 10 days, the ethanol was removed from the
      chambers for 3 days. After the ethanol was returned to the chambers, saline was
      substituted for cocaine for 3 days. Following saline substitution, animals were
      given increased cocaine availability. Before cocaine was made available, rats
      consumed primarily the ethanol solution, averaging 31.7 ml of the 5% solution
      (4.2 g/kg ethanol), 10.2 ml of water and 148 food pellets/day. When cocaine (0.2
      mg/kg per injection, i.v.) was made available, rats self-administered an average
      of 40-85 injections per day. Self-administration of cocaine resulted in small
      decreases in ethanol and food intake, as well as some changes in the pattern of
      ethanol intake. However, removing the ethanol from the chambers had no effect
      upon food and cocaine intake. Substitution of saline for the cocaine altered the
      pattern, but not the amount of ethanol intake. There was a trend toward increased
      ethanol intake during the study, which may have been related to repeated cycles
      of cocaine availability.

PMID- 8261888
TI  - The medical status of methadone maintenance patients in treatment for 11-18
      years.
AB  - To assess the safety and potential health consequences of long-term methadone
      maintenance treatment, we identified 111 male patients admitted to methadone
      maintenance treatment between 1965 and 1968, still enrolled in 1980 and in
      continuous treatment for at least 10 years. We were able, between 1980 and 1985,
      to examine patients or review records of 110 patients (99%). Most medical
      diagnoses, symptomatic complaints, physical examination findings and laboratory
      test results occurred with similar frequency in the long-term methadone
      maintenance patients and in a group of 56 long-term heroin addicts. These data
      suggest that prolonged methadone maintenance treatment is safe and is not
      associated with unexpected adverse effects.

PMID- 8261889
TI  - Psychosocial correlates of alcohol, tobacco and cannabis use: findings from a
      Nigerian university.
AB  - The possible correlates of alcohol, tobacco and cannabis use were investigated in
      a survey conducted among undergraduate students of the University of Ilorin,
      Nigeria. Factors that emerged as common correlates to the three substances
      investigated were peer influence, self-reported poor mental health, religiousity,
      parental/guardian supervision, perceived availability and perceived harmfulness.
      In addition, drinking and smoking were found to be commoner among the male sex
      and among respondents who reported study difficulty. There was also a significant
      positive relationship between cannabis use and a polygamous family background and
      belonging to an older age group. Although the data used in the analysis is
      limited due to its cross-sectional nature, the observations made are useful
      enough for the formulation of primary prevention strategies. A further and more
      elaborate longitudinal study is, however, suggested.

PMID- 8261890
TI  - A comparison of alcohol consumption between lesbians and heterosexual women in an
      urban population.
AB  - An elevated rate of alcohol problems is believed to exist in the gay and lesbian
      community. However, prevalence estimates suggesting this have generally been
      based on convenience samples which have over-represented bar patrons and clinical
      sources. Recent epidemiological studies examining risk factors for AIDS have
      gathered information on alcohol consumption as well as sexual orientation. Data
      based on improved sampling methods are now available for estimating drinking
      rates of lesbians and gay men. This study compares the drinking patterns of
      heterosexual women and lesbian/bisexual women who were recruited through a random
      sampling design in San Francisco, CA. Contrary to previous research, no
      statistically significant differences in alcohol consumption and drinking
      patterns between these two groups were found.

PMID- 8261891
TI  - Allelic association of the D2 dopamine receptor gene with cocaine dependence.
AB  - The objective of the present study was to examine allelic prevalence of the D2
      dopamine receptor (DRD2) gene in male cocaine-dependent (CD) Caucasian (non
      Hispanic) subjects and to determine the relationship of DRD2 alleles to family
      history and selected behavioral measures. The prevalence of the A1 allele in CD
      subjects (n = 53) was 50.9%. It was significantly higher than either the 16.0%
      prevalence (P < 10(-4)) in non-substance abusing controls (n = 100) or the 30.9%
      prevalence (P < 10(-2)) in population controls (n = 265) wherein substance
      abusers were not excluded. Similarly, a significantly higher prevalence (P < 10(
      2)) of the B1 allele was found in CD subjects (n = 52) compared with non
      substance abusing controls (n = 53); 38.5% vs. 13.2%. Logistic regression
      analysis of CD subjects identified potent routes of cocaine use and the
      interaction of early deviant behaviors and parental alcoholism as significant
      risk factors associated with the A1 allele. The cumulative number of these three
      risk factors in CD subjects was positively and significantly (P < 10(-3)) related
      to A1 allelic prevalence. The data showing a strong association of the minor
      alleles (A1 and B1) of the DRD2 with cocaine dependence suggest that a gene,
      located on the q22-q23 region of chromosome 11, confers susceptibility to this
      drug disorder.

PMID- 8261892
TI  - Daily cigarette consumption in early adulthood: age of smoking initiation and
      duration of smoking.
AB  - This study considers the extent to which daily consumption of cigarettes in young
      adults varies by age at first cigarette and duration of smoking. Data come from a
      random sample of 21- to 30-year-old members of a large HMO in the Detroit area.
      Daily cigarette consumption by current smokers varied by duration of daily
      smoking: the longer the duration, the higher the number of cigarettes smoked.
      Duration from first cigarette to daily smoking bore no relationship to cigarette
      consumption. When duration of daily smoking was statistically controlled, the
      association between cigarette consumption and age at first cigarette was not
      statistically significant. The findings suggest that public health efforts to
      delay daily smoking among adolescents might reduce cigarette consumption in early
      adulthood.

PMID- 8261894
TI  - [Whereto and why do we rehabilitate sick children and adolescents].

PMID- 8261893
TI  - [Study program "Nursing/Nursing Management". Curricular concept].

PMID- 8261895
TI  - [Family-oriented care in the pediatric hospital. An answer to shortcomings of
      medical treatment systems].

PMID- 8261896
TI  - [The family as the most important relational environment for the chronically ill
      child].

PMID- 8261897
TI  - [Luftiku(r)s, an asthma training course for afflicted families].

PMID- 8261898
TI  - [Nursing home "haus der kinder". Experiences on the course of rehabilitation from
      a center for the aftercare for children with heart disease and their parents].

PMID- 8261899
TI  - [The right to custody of minor children].

PMID- 8261900
TI  - [Academization of nursing--does it correct the nursing shortage?].

PMID- 8261901
TI  - [Nursing tasks in anorectic female patients. Presentation on the basis of
      activities of daily living].

PMID- 8261902
TI  - [Not just the "baby blues".... Introduction of a psychiatric department which
      accepts mothers with a postpartum psychiatric disorder together with their
      babies].

PMID- 8261903
TI  - [Parallel infusions. Tips for their use].

PMID- 8261904
TI  - [The problem of the danger of dogs; a study of incidents with dogs in a large
      city].
AB  - Incidents with dogs present a public problem. In order to specify this, all
      recorded cases of dog bites in the city of Munich from 1986-1991 (n = 284) were
      registered. The range of injury of men and animal, the influence of breed, age
      and sex of the dog on the incident, the behaviour of the owner in the situation
      and the location were inquired. 207 people have been lightly wounded. 136 dogs
      have been injured. The most incidents occurred with German Shepherds, mixed
      breeds of German Shepherds, Boxers, Rottweilers, Doberman Pinschers, Great Danes
      and Bull terriers. Almost one third of the dogs have been involved in cases of
      recurrence. There has been a distinct influence of the owner on the behaviour of
      the dogs. The reaction of the owner has got significant influence of the kind,
      frequency and seriousness of the accident. The spectrum reaches from passive
      watching of the incidence to encouraging the dog to bite. Most owners did not
      absolve any kind of educational program with their dog. More than 50% of the dog
      owners were judged incompetent to lead their dog in an expert opinion and two
      third of the owners considered themselves unsuitable to lead a dog. Almost 90% of
      the dogs have not been on a leash. Most of the incidents took place in public
      places and only 9% happened in parks. A catalogue of possible measures to avoid
      such incidents will be presented.

PMID- 8261905
TI  - [Development of an enzyme-linked immunosorbent assay for the detection of
      antibodies against bovine herpesvirus type 5 (BHV-5) in sheep sera].
AB  - The indirect enzyme-linked immunosorbent assay (ELISA) was first developed for
      the detection of antibodies against BHV-5 in sheep sera. Investigations of
      various antigen (Ag) preparations revealed that BHV material which had been
      purified across a sucrose gradient using sonification followed by
      ultracentrifugation gave satisfactory results during application in ELISA.
      Optimal coating of the solid phase was achieved with Ag adsorption at 4 degrees C
      overnight with 5 micrograms of virus material/ml in a carbonate-bicarbonate
      buffer, pH 9.7. The background reactions were significantly reduced by blocking
      the free bonding points with 1% gelafusal after Ag adsorption. As the extinction
      values of all the sera investigated which a dilution of 1:50 or more below 0.2,
      the difference threshold between positive and negative sera was set at 0.2. A
      total of 490 sera from various stocks of sheep were investigated with regard to
      the occurrence of antibodies against BHV-5 in ELISA. The growing rate of
      infection with herpesviruses among ruminants and the subsequent economic loss
      have resulted in the increased significance in the last few years of bovine
      herpes-virus (BHV) disease.

PMID- 8261906
TI  - Comparative neuromuscular blocking potency of pipecuronium and pancuronium.
AB  - The effects of pipecuronium bromide (Pi.) and pancuronium bromide (Pa.) on the
      contractile response of rat-phrenic nerve diaphragm and frog's musculus rectus
      abdominis preparation were studied. Pi. and Pa. were found to have a dose
      dependent reduction in the contractile response of the tested preparation. Trials
      were made to estimate the potency of Pi. in a comparison with Pa. In this respect
      Pi. exhibited a more potent effect than Pa. The duration of action is about twice
      as long as that of Pa. in equieffective doses. Neostigmine rapidly and completely
      antagonises the neuromuscular blockade caused by Pi. and Pa.

PMID- 8261907
TI  - [Struvite calculi dietetics: 2. Effect of ammonium chloride and carbonates on the
      acid-base and mineral balance of cats].
AB  - Six healthy adult cats were fed a basal minced beef meat and rice diet with
      varying amounts or combinations of acidifying and alkalizing additives (ammonium
      chloride, calcium and sodium carbonate). The base excess in the food (mmol/kg dry
      matter) was calculated (data on food compounds in g/kg dry matter) as follows:
      base excess = 49.9*Ca + 82.3*Mg + 43.5*Na + 25.6*K - 64.6*P - 13.4*Met
      16.6*Cystine -28.2*Cl. It amounted to between +305 and -1079 mmol/kg dry matter.
      Urine and blood pH as well as balance of minerals and water were determined in
      the cats. The mean urine pH ranged between 6.1 and 7.8. There was a highly
      significant correlation between the base excess in the food and the mean urine
      pH. The regression line was linear down to a base excess in the diet of about 
      400 to -500 mmol/kg dry matter and a pH in the urine of 6.2. The postprandial
      increase of urine pH was suppressed either by large amounts of ammonium chloride
      (> 780 mmol/kg dry matter) alone or in combination with calcium carbonate, but
      not in combination with sodium carbonate. The relationship between the decrease
      of the blood pH and the amount of ammonium chloride added to the diet was more
      marked than the relationship between blood pH and base excess in the food. In
      order to avoid health risks by long term application of acidifying diets it is
      recommended to formulate struvite diets with low base excess in such a way, that
      they contain as few alkalizing compounds as possible, which must be neutralized
      by acidifiers.

PMID- 8261908
TI  - [Analysis of environmental and genetic influences on the urea and acetone content
      in milk from the breeds German spotted cattle and German brown cattle].
AB  - In total, records of 915 cows of the breed German Simmental and German Brown were
      available to investigate the influences of herd, month, lactation number, stage
      of lactation, milk production, diseases at calving, breed-Brown-Swiss blood
      proportion and additive-genetic effect of the cow on milk urea and acetone
      content. Significant differences between herds, months and lactation numbers
      could be shown for milk urea and acetone content. Acetone content decreased
      significantly in the first 100 days post partum by 0.06 mmol/l. Milk fat content
      was significantly correlated with milk urea and acetone. The heritabilities for
      milk urea were estimated in German Simmental cows as h2 = 0.06 +/- 0.04 and in
      German Brown cows as h2 = 0.25 +/- 0.11. Using milk samples up to 50 days post
      partum, heritability estimates were between h2 = 0.10 +/- 0.09 and h2 = 0.17 +/-
      0.12 in German Simmental cows.

PMID- 8261909
TI  - [The effectiveness of clanobutin for the prevention of postpartum primary ketosis
      in dairy cows].
AB  - Investigations on the efficacy of Clanobutin for prophylaxis of postpartum
      primary ketosis were performed in dairy cows. No one cow in the group of 15
      treated animals diseased by ketosis, but 2 of 15 control animals showed signs of
      primary ketosis. The results show the good efficacy of Clanobutin for prophylaxis
      of postpartum primary ketosis in dairy cows.

PMID- 8261910
TI  - [The use of the HET-CAM test for the determination of the irritating effects of
      humic acids].
AB  - Using the synthetic humic acid product HS 1500 and the native product Sodium
      Humate, the suitability of the HET-CAM-test to evaluate irritating effects was
      tested. Neither sensitizing nor irritating properties were detectable in
      concentrations of up to 10% in either humic acid solution. This leads us to the
      conclusion that both products are very mildly acting substances on mucous
      membranes and skin, causing no irritative effects. In order to improve the
      certainty of these results, it is still currently recommended to carry out the
      Draize-test in addition to the HET-CAM procedure (SPIELMANN, 1992). We are
      convinced that the HET-CAM-test can be a very useful first step in distinguishing
      between irritative and non irritative substances and in protecting animals from
      pain, even in the event that the results of both tests do not clearly correspond
      to each other. Taking into account the results of our experiments, a modified HET
      CAM-test also seems to be useful to predict the antiphlogistic effects of
      chemical substances.

PMID- 8261911
TI  - [Paths of food hygiene in Poland].
AB  - Varying economic conditions and management systems in different countries have
      determined the foundation of legal regulations for sanitary food control. The
      legal system in Poland in the years 1795-1928 was subject to the laws of three
      partitioning powers: Prussia, Russia and the Austro-Hungarian Empire. On March
      28, 1928, the President of Poland passed three decrees equivalent to acts which
      had a significant impact on sanitary food control. The decrees took into account
      the following issues: animal protection, food products inspection and evaluation
      of slaughter animals and meat. For the people of Poland, who in the first half of
      the 20th century lived within the boundaries drawn by the partitioners, it was
      important that the legal systems had been based on German law, regarded the best
      possible at that time. Although the decrees were based on Prussian and Austrian
      regulations, the infrastructure of food production, of food trade and hygiene in
      Poland until 1945 was built on the Russian administrative foundation (2/3 of
      Polish territory) (Fig. 1). After World War II, the economic system established
      in Poland was subordinate to Soviet rules. This included food manufacturing
      plants as well as the system of food control. In 1989 Poland came through deep
      political and economic changes, but the legal system has remained the same.
      However, there are disputes about the scope between the National Hygiene
      Inspectors (PIS) operating under the Ministry of Health and Veterinary Hygiene
      Inspectors (WIS) subject to Woivod's Office.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261912
TI  - [Parasitological fecal studies of equids, dogs, cats and hedgehogs during the
      years 1984-1991].
AB  - The results of the coproscopical examinations in horses, dogs, cats and hedgehogs
      between 1984 and 1991 are presented. In 9192 samples from horses 55.5% stages of
      strongylids, 4.0% of Parascaris equorum, 2.2% of anoplocephalids, 1.6%
      Strongyloides westeri, 0.7% of Oxyuris equi, 0.6% of Eimeria leuckarti, 0.2% of
      Fasciola hepatica and 0.04% of Dictyocaulus arnfieldi were found. In 48.0% of the
      46 samples from donkeys eggs from strongylids were detected, in 17.4% larvae from
      Dictyocaulus arnfieldi, in 2.2% eggs from Strongyloides westeri, Parascaris
      equorum and oocysts from Eimeria leuckarti, respectively. In 3329 samples of dogs
      6.9% developmental stages of Toxocara canis, 6.0% of Giardia spp., 4.2% of
      Isospora spp., 3.0% of Sarcocystis spp., 2.5% each of ancylostomids and Trichuris
      vulpis, 1.1% of Toxascaris leonina and 1.1% of Dipylidium canium, up to 1.0% of
      taeniids, 0.6% of each Mesocestoides spp. and Metastrongylidae, 0.3% of
      Strongyloides stercoralis and 0.2% of Capillaria spp. and Hammondia heydorni were
      detected. In 9.5% of the 1147 samples of cats eggs from Toxocara mystax were
      found, in 4.7% eggs of taeniids, in 4.6% cysts of Isospora spp., in 2.4% of
      Giardia spp., in 1.4% eggs of Dipylidium caninum, in 1.0% of Capillaria spp. and
      Aelurostrongylus abstrusus, in 0.6% development stages of Toxoplasma gondii, in
      0.5% of ancylostomids and in 0.3% of Sarcocystis spp. and Opisthorchis felineus.
      In 1175 samples of hedgehogs 48.8% eggs of Capillaria spp., 35.9% of Crenosoma
      striatum, 17.9% oocysts of Isospora spp., 2.3% eggs of Brachylaemus erinacei were
      found.

PMID- 8261913
TI  - [Causes of losses in a pig fattening facility].
AB  - Losses of fatteners in a pig-husbandry were monitored over a one year period. All
      fatteners which perished or were slaughtered prematurely were taken into
      consideration. Out of 10,485 fatteners six hundred (5.7%) pigs were lost
      prematurely. Of these animals, 360 (60.0%) were slaughtered, and 240 (40.0%)
      died. Diseases of the respiratory system were the most frequent drop-out reason
      (32.3%). Pneumonia (mostly pleuropneumonia) was diagnosed in 90.7% of these
      animals. Thirty one percent of the lost fatteners had diseases of the locomotor
      system. Of these disorders, 73.1% affected the skeleton and joints, and in 26.9%
      PSE-syndrome was found. Other disorders were: diseases of the cardiovascular
      system (13.7%), intestinal tract (10.0%), urogenital tract (1.2%), skin (1.5%),
      and diseases of other specific organs (5.7%). Cannibalism was found in 2.3% of
      the lost fatteners, unthriftiness in 1.0%, and in 1.3% the cause of the loss
      could not be identified. The greatest numbers of fatteners were removed during
      the cold season, particularly in September. Most of the lost pigs (53.3%) had a
      body mass between 31 and 60 kg. The highest drop-out rates were found during
      weeks 2 to 6 and 9 to 12 of the fattening period.

PMID- 8261914
TI  - [Estrus synchronization and insemination results in Arabian mares in the
      Eskisehir stud].
AB  - An Arab broodmare herd of 30 mares age ranging from 4 to 12 years was grouped
      into 3 groups (group A, B, C) with 10 mares each and exposed to three different
      methods of cycle synchronisation. Group A mares received two PGF2 alpha
      injections 14 days apart. Group B mares got additionally 2,500 IU of hCG 5 days
      after second prostaglandin application. Group C consisted of mares which had
      foaled in a synchrony of one week and got a PGF2 alpha injection 3 weeks after
      parturition. All the mares responding to synchronisation were inseminated closely
      to ovulation detected by serial rectal palpations with an insemination doses of
      0.5 billion of progressively motile spermatozoa. Conception control was performed
      on the 18th day after ovulation to be continued up to pregnancy confirmation on
      day 60. Synchronisation response in the different groups A, B, C was 60, 80, 80%
      starting first oestrus signs between 24 to 36 hours and ovulation time between 5
      to 6.5 days post last PGF2 alpha application. Pregnancy rate (first cycle) was
      66.7% (A), 75% (B) and 87% (C) basing on the number of mares who responded to
      synchronisation exposure.

PMID- 8261915
TI  - [Physiological function of the gastrointestinal tract and pathophysiological
      changes in neonatal diarrhea of calves].
AB  - Firstly, the basic principles of absorption and secretion in the intestine of
      healthy animals are described. The etiology and the pathophysiologic mechanisms
      of neonatal diarrhea in the calf due to E. coli and rota-/coronavirus are
      discussed. Enterotoxins of E. coli stimulate primarily the secretion of chloride
      (and thereby water) in the small intestine without damaging the intestinal
      mucosa. The sodium-dependent transport systems for the absorption of glucose and
      amino acids remain intact. In contrast, infections with rota- or coronavirus lead
      primarily to a disturbance of absorption processes in the intestine due to
      villous atrophy. Crypt cells are indirectly affected by inflammation mediators.
      Intestinal motility is inhibited during most diarrheic episodes; the application
      of para-sympatholytics in therefore not favourable.

PMID- 8261916
TI  - [Comparative studies of the detection of antibodies against BHV-5 using the
      enzyme-linked immunosorbent assay, serum neutralization test, cell assay and
      immunofluorescence test].
AB  - A comparison of the analyses of 490 serum samples from various flocks of sheep
      for the detection of BHV-5 antibodies using ELISA, serum neutralisation test,
      cell assay and immunofluorescence assay showed nearly identical results regarding
      the distinction between positive and negative serum samples. The percentage of
      serum samples with antibodies against BHV-5 antigen differed from test to test:
      ELISA 268 (54.7%), cell assay 323 (65.8%), immunofluorescence assay 222 (46.6%)
      and serum neutralisation test 221 (45.1%). With ELISA, cell assay and
      immunofluorescence assay the experiment can be carried out more simply and
      rapidly than with serum neutralisation test.

PMID- 8261917
TI  - [Malformations of the heart and endocardiosis in swine].
AB  - The authors describe in 321 of 170,000 examined slaughter pigs certain cardiac
      malformations which were associated with endocardiosis of the mitral valve.
      Aortic stenosis was associated with endocardiosis of the aortic valve. It is
      assumed that in certain breeds of swine a congenital predisposition for
      impairment of the collagen metabolism may support the development of
      endocardiosis.

PMID- 8261918
TI  - [Comparative studies of commercial breeding methods for game pheasants (Phasianus
      colchicus spec.) with regard to the animal welfare aspects of extensive and
      intensive husbandry].
AB  - The study presents the effects that different rearing methods of commercial
      pheasantries have on pheasants. The techniques applied by 17 commercial
      pheasantries in Northern Germany are specified. These techniques were exemplarily
      simulated on pheasants reared under defined conditions in special aviaries. The
      results illustrate the impact of the different rearing methods on the condition
      and constitution on the birds seen from the point of view of animal welfare. Only
      about 35% (20,400) of all pheasants reared (85,000) in commercial pheasantries
      were kept under conditions which allowed a physical and behavioural development
      that nearly complied with the stipulation of the animal protection laws. In
      approximately 65% of all the pheasants were not enabled to adapt themselves to
      the food or climate of the habitat they would have to live in after their
      release. The study proves that most of the currently applied rearing techniques
      as well as the methods for preventing feather picking are not compatible with the
      law on the protection of animals.

PMID- 8261919
TI  - The determination of diethylstilbestrol (DES) in the faeces and tissues of
      chickens treated with DES and in the faeces and tissue samples of calves, lambs
      and chickens collected from various areas of Turkey.
AB  - Diethylstilbestrol (DES) analyses were carried out on muscle, liver, kidney and
      faeces samples of 20 control and 20 experimental broilers to which 5 mg DES/day
      had been given orally for a period of 7 days. The treated samples were analysed
      using the Radioimmunoassay method. The removal time of DES from the tissues was
      determined. Five days following the final administration of DES, its faecal
      concentration was 151 ppb. However, 7 days after the final administration faecal
      DES concentrations increased again. On the first day after the final DES
      administration, DES concentrations in the liver, muscle and kidney were 0.78,
      0.74 and 1.33 ppb, respectively. While these values measured on the final day
      were within the range of the control values. There was an increase of DES in
      plasma at the end of the experimental period. A total of 1811 muscle, liver,
      kidney and faeces samples of calves, lambs and chickens and feed samples
      collected from various areas in Turkey were analysed for the presence of DES.
      Positive samples for chicken feed was 36.9%. Also 1.9% of the chicken faeces
      samples were DES positive. All other samples were negative for DES.

PMID- 8261920
TI  - Isolation of Chlamydia spp. from ostriches (Struthio camelus) (short report).
AB  - Post mortem examination of ostrich chicks (Struthio camelus) originating from a
      flock with a high mortality rate is described. The main pathological lesions
      found, indicated colibacillosis which was further corroborated by the isolation
      of pure culture E. coli. Furthermore Chlamydia spp. was isolated for the first
      time from ostriches. A detailed isolation procedure is presented. The association
      of colibacillosis with Chlamydia and the latency of Chlamydia is discussed.

PMID- 8261921
TI  - [A striking malformation in a spotted rabbit].

PMID- 8261922
TI  - Tonsillectomy.

PMID- 8261923
TI  - Toxoplasmosis appearing as an anterior neck mass.

PMID- 8261924
TI  - Dry central tympanic membrane perforation.

PMID- 8261925
TI  - Multilobulated hemorrhagic vocal fold cyst.

PMID- 8261926
TI  - Endoscopic view of the middle turbinate.

PMID- 8261927
TI  - Mycobacterial cervicofacial adenitis--changing concepts.

PMID- 8261928
TI  - Neuroma of the chorda tympani nerve.
AB  - The authors present a case of Neuroma of the Chorda Tympani Nerve, which is
      extremely rare. Apparently, only two (2) cases have been reported to date. The
      initial manifestation was a hard tumor that occupied the posterior wall of the
      external auditory canal. There were no other symptoms.

PMID- 8261929
TI  - Mycobacterial cervical adenitis in children: medical and surgical management.
AB  - This is a review of the treatment results of cervicofacial mycobacterial adenitis
      in 85 children and adolescents. Twenty-three patients were treated with only anti
      tuberculous medications (Group A). Thirteen underwent surgical procedures at the
      time of presentation for drainage of abscess or diagnostic biopsy, followed by
      treatment with anti-tuberculous medications (Group B). Forty-nine were initially
      treated with anti-tuberculous medications, with or without needle aspirations,
      and subsequently required surgery for one of the following reasons: 1) drainage
      and/or excision of abscess (Group C); 2) diagnostic biopsy (Group D); and 3)
      excision of persistent, enlarging, or recurrent nodes, or of draining fistulas
      (Group E). Four patients who were initially treated with surgery required a
      second procedure for persistent or recurrent disease. The cure rate for patients
      treated only with medications (Group A) was 95%. The cure rate for patients in
      the surgical groups after the initial procedures were 50% for Group B, and 100%
      for Groups C, D, and E. The overall cure rate was 92% for surgical treatment
      groups B-E and 93% for all 5 treatment groups. The clinical features of the
      disease, treatment outcome, and guidelines for management are discussed.

PMID- 8261930
TI  - Solitary extramedullary plasmacytoma of the oropharynx: a rare location.
AB  - We describe a case of solitary extramedullary plasmacytoma of the oropharynx
      growing on the left posterior tonsillar pillar. The clinical picture was
      difficulty in swallowing caused from the partial obstruction of the area and
      bleeding from the ulcerated tumor. Lambda light chains were identified on
      immunohistochemical staining but they were not detected in either serum or urine
      (non-secreting tumor). Excisional biopsy followed by radiation therapy were used
      for treatment. Long-term follow up for several years is necessary in order to
      rule out evolution to multiple myeloma.

PMID- 8261931
TI  - The enlarged vestibular aqueduct syndrome (EVA syndrome).
AB  - The presentation to the Department of Pediatric Otolaryngology at the Children's
      Hospital of Michigan of a series of patients with sensorineural hearing loss and
      enlargement of the vestibular aqueduct prompted exploratory tympanotomy in three
      patients (two unilateral and one bilateral), for a total of four ears. These
      explorations were prompted by progression and/or fluctuation of hearing levels.
      The discovery of abnormal round windows in all four ears with a post-traumatic
      fistula present in one ear suggested the presence of a new association. A
      previously undescribed association of an enlarged vestibular aqueduct,
      sensorineural hearing loss and round window abnormality with potential fistula
      formation was identified. A review of the anatomy and physiology, literature
      review, and a prospective analysis with discussion of eight patients with
      enlarged vestibular aqueduct syndrome evaluated and treated at Children's
      Hospital of Michigan, is presented. We conclude that all children with
      sensorineural hearing loss should undergo extensive evaluation to determine
      etiology, including radiographic studies of the temporal bone. Further, the
      presence of an enlarged vestibular aqueduct should prompt the otolaryngologist to
      consider the presence of a round window abnormality and the potential for
      predisposition to perilymph fistula.

PMID- 8261932
TI  - Protrusion of postoperative maxillary sinus mucocele into the orbit: case
      reports.
AB  - Maxillary sinus mucocele, which appears more than 10 years after Caldwell-Luc
      surgery, is very rare in the United States or Europe. However, it is very common
      in Japan. It is called "postoperative maxillary sinus mucocele" or "postoperative
      maxillary cyst." In this paper, postoperative maxillary sinus mucoceles, which
      protruded into the orbits, are reported. One patient, a 50-year-old man,
      underwent Caldwell-Luc surgery 31 years ago, and the other patient, a 61-year-old
      woman, underwent Caldwell-Luc surgery at the age of 18. The incidence of this
      disease, symptoms, diagnosis and treatment are discussed in this paper.

PMID- 8261933
TI  - Nasopharyngeal perforation as a complication of nasogastric intubation.
AB  - We report a patient with nasopharyngeal perforation associated with nasogastric
      intubation. Diagnosis of the perforation was accomplished by roentgenograms of
      the neck and identification of the site by fiberoptic endoscopy and a water
      soluble radiographic contrast agent. The extent of subcutaneous emphysema and
      lack of extraluminal fluid collections was documented by CT scan. Early diagnosis
      allowed for successful treatment with intravenous antibiotics.

PMID- 8261934
TI  - Esophageal foreign body after smoking crack cocaine.
AB  - Injuries from cocaine abuse are often seen and have been reported more often with
      the introduction of crack cocaine. Burns of the upper aerodigestive tract have
      been reported but no reports of esophageal obstruction have been located. We
      report ingestion of a foreign body from smoking crack cocaine and our management.
      A review of other possible aspiration and ingestion injuries is included.

PMID- 8261935
TI  - Cardiothoracic surgery in sub-Saharan Africa: problems and perspectives.

PMID- 8261936
TI  - Thoracic trauma in Nigerians: an eight year experience.
AB  - An eight-year combined retrospective and prospective review of thoracic trauma
      patients managed at the University of Ilorin Teaching Hospital, Ilorin, Nigeria
      between 1979 and 1986 is presented. Among 239 patients fully reviewed, were 189
      (79.1%) males and 50 (20.9%) females. Mean age was 29.4 +/- 14.6 years. Road
      traffic accidents caused injuries in 72% of patients. The need for non-operative
      care, limited or extensive operations reflected severity of trauma except that
      eight severely injured patients were dead on arrival and another 12 were alive on
      arrival but died during resuscitation. Overall thoracotomy and mortality rates
      were 5.4% and 15.3% respectively. Unlike experience in developed countries there
      is a low incidence of penetrating, occupational and heart injuries and a high
      percentage of fractures of proximal ribs without associated aortic or bronchial
      ruptures. There is also a high incidence of multiple trauma.

PMID- 8261937
TI  - Closed mitral valvotomy at Kenyatta National Hospital.
AB  - Analysis of data concerning 24 patients with mitral stenosis treated surgically
      is presented. Twenty patients had closed valvotomy with good results in 19 of
      them. One patient died post operatively from cerebral embolism. Closed mitral
      valvotomy is recommended in selected cases.

PMID- 8261938
TI  - Surgical management of pyopericardium.
AB  - Forty three patients with pyopericardium were managed over a six year period.
      Pyomyositis and septic arthritis were the most common associated conditions and
      Staphylococcus aureus the commonest microorganism isolated. Mycobacterium
      tuberculosis was isolated in only three of the cases. Pericardiocentesis and
      various forms of pericardial windows were found to be associated with high rates
      of recurrences, inadequate drainage and subsequent constrictive pericarditis.
      Pericardiectomy should be done as an initial form of surgical treatment where the
      general condition of the patient permits, since this procedure is not associated
      with the adverse sequelae of aspiration and pericardial window procedures.

PMID- 8261939
TI  - The bronchodilator effect of Garcinia Kola.
AB  - This work investigated the bronchodilator effect of Garcinia Kola (Bitter Kola)
      in normal Nigerians. Nineteen undergraduate male students (17-25 years) were used
      for the study which involved the consumption of Garcinia Kola (15 grammes per
      subject) and the measurement of peak expiratory flow rate (PEFR), forced
      expiratory volume in one second (FEV1) and forced vital capacity (FVC) at
      intervals of 30 minutes up to a maximum of 90 minutes. Each subject served as his
      own control. There was time-dependent increases in the measured parameters.
      However, only the PEFR showed significant (p < 0.05) increase and this was
      observed at the 60th minute. This probably shows a mild bronchodilator effect of
      this Kola.

PMID- 8261940
TI  - Fungal chest infections at the Lagos University Teaching Hospital.
AB  - One hundred and ninety-six sputum specimens were collected from patients with
      suspected fungal chest infections between 1986 and 1989 at the Medical Out
      patients Department of the Lagos University Teaching Hospital. Eighty-three
      fungal isolates were obtained representing 42.3 percent of specimens collected.
      Seventy per cent of the fungal isolates were due to species of either Candida or
      Aspergillus. Whilst the predisposing factors to Aspergillus infection were either
      due to tuberculosis or bronchial asthma, a high proportion of infection with
      Candida were due to patients with leukaemias and lymphomas. Diagnostic
      shortcomings in the cases studied are stressed. The widespread uncontrolled use
      of antibiotics and corticosteroids in Lagos, and the rising incidence of human
      immunodeficient virus infection makes it imperative to routinely investigate for
      fungal chest infections in Lagos.

PMID- 8261941
TI  - The impact of vitamins A,C,E, and selenium compound on prevention of liver cancer
      in rats.
AB  - A study was initiated to determine the impact of vitamins A, C, E, and selenium
      compound (Se) on the prevention of liver cancer. Sixty animals were fed a diet
      with or without these vitamins followed by aflatoxin B treatment for a period of
      24 months. Most of the animals fed a diet devoid of vitamins developed liver
      cancer, while none or only a few of the animals given vitamins suffered during
      this period. We suggest that vitamins can inhibit liver cancer by inducing
      hepatic microsomal enzymes that metabolise aflatoxins to noncarcinogenic
      products.

PMID- 8261942
TI  - Bone changes in sickle cell anaemia.
AB  - Analysis of available radiographs of the skeletal system in 50 patients suffering
      from sickle cell anaemia in the Assir Region (South Western height and valley) of
      the Kingdom of Saudi Arabia taken over a three year period showed a wide spectrum
      of bone changes. Both infarctions and medullary hyperplasia were common,
      producing the usual previously reported changes. Spinal changes, mostly
      osteoporosis and vertebral end plate depression were more prominent in the
      younger age group. Avascular necrosis of femoral head was common and occurred
      earlier than in previous reports in the literature. Humeral head and radial head
      necrosis were also recorded. The overall findings agree with recent reports from
      both the Eastern and Western regions of the Kingdom that bone changes in SCA are
      common and could be more severe than in other countries. Complications such as
      osteomyelitis and fractures were not common.

PMID- 8261943
TI  - Carcinoma of the thyroid in Khartoum.
AB  - One hundred and twelve patients with thyroid malignancy seen at The Radio-isotope
      Centre, Khartoum (RICK) during the period 1982-1989 were studied. The female to
      male ratio was 2.5:1.0 with a high incidence of the disease between the ages of
      40 and 70 years. Follicular carcinoma was the commonest (42%) followed by
      papillary (22.3%) and anaplastic (21.4%). Goitre was the main presenting symptom
      (92.9%). Cervical lymphadenopathy was present almost equally in these three
      histological types, 26.6%, 32%, and 33% respectively. Blood borne metastasis was
      seen in 32 (28.6%) patients in the whole series. Follicular carcinoma had the
      highest incidence of blood borne metastasis (21 out of 47 patients) being mostly
      osseous (16 patients). Anaplastic and squamous cell carcinoma showed a locally
      aggressive behaviour to nearby structures resulting in hoarseness of voice,
      dyspnoea and dysphagia indicating advanced disease. Most patients presented with
      advanced disease limiting the option of total thyroidectomy (40%). A high index
      of clinical suspicion is needed in areas of endemic goitres in order that
      selected cases can be subjected to surgery at an earlier stage of the disease.
      Doctors and medical assistants should be taught how to diagnose solitary thyroid
      nodules and clinically hard glands so that they can be evaluated at an earlier
      stage of the disease.

PMID- 8261944
TI  - Patterns of goitre in Sidama Awraja in Ethiopia and its relationship to piped
      water supply.
AB  - A cross sectional study was conducted in 1987 to determine the extent of goitre
      in Awassa Zuria part of Sidama Awraja. Households were the subjects of the survey
      to assess goitre rates. Trained staff were used for interview and clinical
      assessment of goitre rate. Among the total of 2,450 study population surveyed,
      83.9% (n = 2,055) were school children. Out of the total study population, 40.5%
      (n = 993) were positive for goitre and ninety eight cases of the positive school
      children (n = 791) were randomly taken for biochemical tests. The Radio
      immunoassay technique was used to measure the levels of T3, T4 and TSH. The
      Sandell and Kolthoff technique was used to measure urine and water iodine. A
      comparison of T4 results, showed higher results for surface water users than
      piped water users and this has shown a significant difference (P < 0.001). It was
      higher in piped water compared to surface water. Further investigation however is
      required to fully elucidate the picture. Generally it is advisable to start
      iodine prophylaxis program in the studied areas.

PMID- 8261945
TI  - A bioassay to evaluate the efficacy of permethrin-impregnated screens used
      against phlebotomine sandflies (Diptera: Psychodidae) in Baringo District of
      Kenya.
AB  - Control of phlebotomine sandflies remains a difficult problem throughout the
      world because of the insects' very highly specialized breeding sites. Use of
      insecticides remains one effective methods for managing sandflies. The present
      studies were conducted to establish how long permethrin impregnated wall cloth
      remains effective against sandflies. Cotton cloth, impregnated with permethrin
      (0.5g/m2) were hung inside experimental houses in Baringo District, Kenya, for
      the control of sandflies. Small pieces of cloth were cut off from the screen
      every month for 12 months, and bioassayed against sandflies. The cloth was found
      to remain effective against sandflies for 6 months.

PMID- 8261946
TI  - Management of malaria in Zanzibar.
AB  - Malaria remains to be a major cause of morbidity and mortality in most African
      countries. Chloroquine resistance is one of the major contributing factors in
      many parts of the continent. Besides plasmodia parasite mutation, improper
      management of malaria cases and the absence of standardised management guidelines
      for the treatment of malaria may play a role in increasing the existing drug
      resistance. In this retrospective study which involved 400 patients at the
      Mnazimmoja Hospital, Zanzibar, chloroquine was found to be the most popular anti
      malarial drug prescribed to 369 (92.25%) of the patients. A full standard
      chloroquine regimen (25 mg-base/Kg) was provided to about 88.15% (238 out of 270)
      of all admitted patients treated with chloroquine alone or in combination with
      other drugs. Prescriptions of multiple antimalarials at a time were found in 97
      (24.25%) of the cases. The duration of a prescribed chloroquine course was 3 days
      (WHO recommendation) in 289 (78.32%), less than 3 days in 49 (13.28%) and more
      than 3 days in 31 (8.40%) of the patients. The possible roles of under-dosage and
      incomplete courses of physician and self-prescribed chloroquine regimens in
      increasing chloroquine resistance are discussed.

PMID- 8261947
TI  - Dental caries, malocclusion and fractured incisors in children from a pastoral
      community in Kenya.
AB  - The prevalence of dental caries, malocclusion and fractured incisors was
      investigated in 245 children from a pastoral community in Kenya. Forty-eight per
      cent of them were found to be caries-free. The overall mean DMFT was 1.9 (s.d.
      2.7). Among those with caries, the mean DMFT was 3.0 (s.d. 2.0). Fifty-eight per
      cent of the children had malocclusion. Overall, 84% of the sample had Angle's
      Class I, 11% Class II and 5% Class III molar relation. The prevalence of
      fractured incisors was 15%. Most of the fractures were in the maxilla and
      involved enamel only. Minimal treatment had been carried out on the children.

PMID- 8261948
TI  - Radiological findings in edentulous Kenyan patients.
AB  - Seven hundred and seventy five files of edentulous patients seen at the
      Department of Dental Surgery, University of Nairobi were scrutinized for the
      presence or absence of routine radiographs prior to treatment. 180 (23.2%) had
      radiographs. 26% of the radiographs had 51 positive radiological findings. 17.3%
      were roots, 3.9% were unerupted teeth, 6.7% were radiopacities and 0.6% were
      radiolucencies. 52.9% of the radiological findings were in the mandible and 47.1%
      were in the maxilla. In the mandible, 44.4% of the radiological findings were in
      the anterior region and 55.6% were found posteriorly. 66.7% of the maxillary
      radiological findings were in the anterior region and 33.3% were found
      posteriorly. Since some of the positive radiological findings such as the
      retained roots and unerupted teeth might lead to infection, cysts or poor
      dentures fit, it is recommended that whenever possible, all edentulous patients
      be examined radiographically prior to treatment.

PMID- 8261949
TI  - Biocidal effects and residual glutaraldehyde in cellulosic and synthetic
      polymers.
AB  - The amount of leachable glutaraldehyde from medical grade Cuprophan 150PM
      (cellulose based) and AN69S (a copolymer of acrylonitrile and sodium methallyl
      sulphonate) membranes, and polyproprene plates following 72 hr immersion in 2%
      alkaline glutaraldehyde was determined. After rinsing the materials for 30
      minutes in distilled water at 37 degrees C, the mean concentration of leachable
      glutaraldehyde from Cuprophan 150 PM (8. 60 +/- 0.55 micrograms/g) was
      significantly greater than that from AN69S membrane (6.50 +/- 0.60 micrograms/g),
      (p < 0.01). The mean leachable glutaraldehyde from plates was 0.30 +/- 0.15
      microgram/g. There was a significant decrease in the mean leachable
      glutaraldehyde from AN69S (5.35 +/- 0.25 micrograms/g) after second immersion (p
      < 0.05). The concentration of leachable glutaraldehyde in the plates and
      Cuprophan 150PM remained relatively unchanged. Absence of growth following
      infusion of 2% alkaline glutaraldehyde into blood contaminated miniature
      dialyzers containing high microbial loads of selected bioindicator organisms (S.
      aureus, P. aeruginosa, B. subtilis (Var globigii) spores, M. gordonae, A. niger
      spores and attenuated polio virus) demonstrated its effectiveness under
      environmental conditions that were conducive to high resistance. These findings
      indicate that 2% alkaline glutaraldehyde is readily washed from the three polymer
      materials that were studied and its accumulation following repeated exposure was
      not evident. Its application in pre-sterilization treatment of heavily
      contaminated invasive polymer based devices seemed feasible.

PMID- 8261950
TI  - Scleroma in Uganda: a review of 85 cases.
AB  - Biopsy and autopsy protocols revealed that between 1972 and 1981, 85 cases of
      scleroma were diagnosed in Uganda. The disease was found to affect females more
      than males, and was found to be more common in the middle aged. Scleroma occurred
      in the nose in 96% of cases and presented commonly at a late stage. The disease
      was found commonly among the tribes of south western Uganda and Itesot in the
      east. Possible factors associated with the distribution of this disease in Uganda
      are discussed.

PMID- 8261951
TI  - Congenital coronary artery fistula in an Ethiopian child: case report.
AB  - A case of right coronary-artery to right ventricular fistula is described. The
      patient, a 3-year old Ethiopian female child, was asymptomatic. Examination
      revealed a machinery type murmur at the third and fourth intercostal spaces.
      Diagnosis was made by echocardiography, and coronary arteriography, followed by
      successful ligation of the coronary AV fistula. This is a rare congenital
      anomaly. The literature on congenital arteriovenous is briefly reviewed and the
      diagnosis and therapy discussed.

PMID- 8261952
TI  - Application of statistical methods in the papers published in the East African
      Medical Journal (EAMJ) since 1923.
AB  - The subject Statistics was hardly known in the research world at the time the
      EAMJ was being started in 1923. It was at this time, scientists working in their
      field of specialization were busy developing statistical methods with the aim of
      solving problems affecting them in their research work. Using a random sample of
      some of the papers published by the EAMJ, this paper evaluates the usage of
      statistical methods since 1923. Usage was very low before 1965, but started
      picking-up with a rising trend since then but still not impressive. Scientists
      should strive to apply statistical methods correctly in their research work. EAMJ
      should lay more emphasis on statistical refereeing as a policy to raise the
      quality of published papers in the Journal. If statisticians were not available,
      which often may be the case, scientists should be encouraged to show their work
      to other research colleagues working in similar areas, before sending the paper
      to the EAMJ. By adopting this approach, it is possible that the quality of papers
      will go up and the usage of statistical methods will increase.

PMID- 8261953
TI  - Community health in eastern Africa--and the East African Medical Journal's
      contribution over seventy years.
AB  - The East African Medical Journal which started in 1923 has now reached its 70th
      year. To what extent has the journal focused the attention of policy and decision
      makers on the most relevant problems of and solutions for Community Health in
      Eastern Africa? To answer this question this paper surveys the Journal's
      publications on Community Health in four eras into which the 70 years can be
      subdivided. It then tries to match these publications with what has been
      happening in the political field and in the development of health services
      related to community health. The conclusion is that the journal has, in this
      geographical region, been keeping pace with important trends and has been a
      stimulus to the development of improved and more relevant services for
      communities. Although the predominant focus has often been on publications based
      on clinical research in hospital settings, it is hoped that the journal will step
      up even further its publication of papers related to community health and Primary
      Health Care. By doing so it can make an even greater contribution to the health
      and well being of the populations of Eastern Africa and not just to the care of
      individuals who gain access to medical institutions.

PMID- 8261954
TI  - Malaria, quinine and blackwater.

PMID- 8261955
TI  - Evolution of paediatric oncology over the years: overview with a focus on sub
      Saharan Africa and examples from the Kenyan experience.
AB  - In this paper on "The Evolution of Paediatric Oncology Over the Years", a
      historical perspective is outlined regarding the subspecialty of paediatric
      oncology on a global basis. The evolution of paediatric oncology units and their
      role in the progress of cancer management in children is highlighted. It is noted
      that success in the management of cancer in adults has followed the footsteps of
      breakthroughs and success in paediatric oncology. The epidemiology of cancer in
      children in sub-Saharan African and the development of paediatric oncology are
      also highlighted. The development of a paediatric oncology unit at the Kenyatta
      National Hospital in Nairobi, Kenya has been focused on, pointing out challenges,
      constraints and success that are associated in the initiation and nurturing of
      such units in developing countries. Lastly, Burkitt's lymphoma is singled out for
      discussion to illustrate problems that are abound in cancer management in
      children in sub-Saharan Africa.

PMID- 8261956
TI  - Surgery: a historical perspective.

PMID- 8261957
TI  - Epidemiology of cardiovascular diseases in Africa with special reference to
      Kenya: an overview.
AB  - At the beginning of this century, high blood pressure was virtually non-existent
      among the indigenous Kenyans. This phenomenon of normotension continued until the
      Second World War following which the Kenyan African began to exhibit progressive
      rise in blood pressure which was age-related. Similar changes were observed in
      Uganda at the same time. From about 25 years ago, high blood pressure became
      established in Kenya and the neighbouring countries, in particular Uganda. These
      trends have been observed in West Africa notably Ghana, Nigeria, Cote d'Ivoire
      and also in Cameroon and Zaire in the Central African region. Consumption of
      sodium salt and alcohol, psychological stress, obesity, physical inactivity and
      other dietary factors are thought to play important aetiologic role in the
      genesis of primary hypertension in the susceptible individuals. Low blood
      pressure communities still exist scattered all over the world, where blood
      pressure does not seem to rise with age. In Africa these have been observed in
      Kenya, Nigeria, Zaire and Kalahari Desert. They also exist in Pacific island,
      Australia, South America and elsewhere. Rural-urban migration coupled with
      acculturation and modernization trends have some relationship with the
      development of high blood pressure as observed in Kenyan and Ghanian
      epidemiologic studies.

PMID- 8261958
TI  - Evolution of nephrology in east Africa in the last seventy years--studies and
      practice.
AB  - Interest in renal disease and practice in East Africa started as far back as the
      first quarter of this century. Work in this colonial era concentrated on
      establishing the existence of renal diseases and identifying the nature and
      incidence of these diseases. This was achieved by case identification and
      reporting as well as retrospective studies on post mortem and medical notes. The
      post independence period has not only identified the existence of even more renal
      diseases but also concentrated on getting a deeper understanding of the
      aetiology, nature, pattern, regional variations, complications and outcome of
      these diseases as seen in our environment. Apart from the better understanding of
      the prevalent renal diseases, emphasis has also been put on the expansion and
      delivery of renal services. Investigative and treatment facilities have been
      improved and a lot has been put into the training of the required local team of
      experts to man these services. This article reviews what has gone on in the last
      70 years from the pure case-report and postmortem reports era to the era of
      locally available modern facilities including haemodialysis, peritoneal dialysis
      and kidney transplantation.

PMID- 8261959
TI  - Periodontal health status in Africa after decades of development.
AB  - As at independence in the sixties and seventies, few countries in Africa had
      dental institutions to train oral health personnel. None can claim to have done
      national dental surveys. By 1979, most countries were reported to have no
      organized dentistry. Literature reports on the prevalence of periodontal diseases
      in Africa indicated that it was among the highest in the world. Therefore, this
      paper reviews epidemiological studies that have been done in the last 33 years or
      so, in an attempt to shed some light on the improvement of periodontal health
      status if any, that has taken place. It is concluded that there is no evidence to
      show that periodontal health status has improved during this period of
      development.

PMID- 8261960
TI  - The status of epidemic diseases--1923 and 1993.

PMID- 8261961
TI  - Management of recurrent cervical cancer: the place of ultra-radical surgery.
AB  - Although mortality from cervical cancer has decreased substantially the incidence
      of recurrent disease, at 35-50%, remains unaltered. Many more young patients are
      seen with recurrent cervical cancer today. This paper reviews this problem--its
      diagnosis and available modes of treatment. The place of re-irradiation,
      chemotherapy and ultra-radical surgery are discussed and their limitations
      highlighted. Better patient selection and individualised treatment planning are
      emphasised. Newer, more objective prognostic indicators based on molecular
      understanding of cancer cells are mentioned as hopeful means through which
      patient selection and treatment could be improved in the future. In the
      developing world where persistent or recurrent disease is more common, the
      situation is unlikely to improve soon.

PMID- 8261962
TI  - Induced abortion in sub-Saharan Africa.
AB  - Unsafe abortions and their complications are a major cause of maternal mortality.
      Hospital based studies from most African countries confirm that up to 50% of
      maternal deaths are due to abortion. This paper reviews problem of induced
      abortion in sub-Saharan Africa. Issues of prevalence and prevention are addressed
      while acknowledging the need to review the legal regimes operating in these
      countries.

PMID- 8261963
TI  - Seventy years of the East African Medical Journal towards safe motherhood.
AB  - Obstetrical and gynaecological articles related to safe motherhood published in
      the East African Medical Journal between 1924 and 1989 were reviewed. A total of
      133 topics were published. Out of these, 84 (63.2%) were obstetrical and 49
      (36.8%) gynaecological. Out of the obstetrical topics, 66 were pregnancy related,
      12 were public health and the rest medical topics. A rapid increase in the number
      of the relevant topics is seen especially after 1970. This is probably due to the
      increase in the number of of obstetricians training locally in the African region
      and the international nature of the Journal during the last two decades.

PMID- 8261964
TI  - Surgical contraception: the kindest cut of all?

PMID- 8261965
TI  - Minilaparotomy female sterilisation in clients with lower midline abdominal scar.
AB  - A total of 1221 female clients were sterilised via minilaparotomy under local
      anaesthesia as outpatients. 101 of these clients had lower midline abdominal
      scars, 1120 did not. The first group had slightly increased minilap incision
      length, duration of surgery and amount of local anaesthesia required compared to
      the second group but the differences were not clinically significant. The "scar
      group" also tended to have wider ranges for these same parameters, and there was
      one case of abandoned procedure. The incidence of peri-operative complications
      was low, and most of these were minor transitory grievances--the incidence was
      slightly more in the previous scar group. Minilap female sterilisation under
      local anaesthesia is safe and suitable even for clients with a lower midline
      abdominal scar, but good counselling and meticulous client selection is a
      prerequisite.

PMID- 8261966
TI  - Involvement of a community in schistosomiasis control: a Kenyan experience.
AB  - This paper illustrates how community participation was achieved in a study that
      was carried out between 1983-1988 whose general objective was to reduce the
      transmission of schistosomiasis in a rice irrigation scheme in Kenya. A community
      of 2,219 people was mobilized through health education, to effect changes in
      behaviour regarding water contact, water use and faecal disposal. Health
      education, alternative water sources, latrines and mass chemotherapy with
      praziquantel were the schistosomiasis control strategies utilized in this study.
      By the end of 2 years, the canals were cleared of their thick vegetation, water,
      sanitation, bathing and washing facilities were constructed, water contact with
      infective waters was reduced, faecal contamination of water was reduced, the
      people's knowledge on schistosomiasis increased and the rate and intensity of
      schistosomiasis infection was reduced. The study demonstrated that it is possible
      to fully involve the community in disease control efforts.

PMID- 8261967
TI  - Knowledge, attitudes and practices (KAP) of human intestinal helminths (worms) in
      two rural communities in Nyanza Province, Western Kenya.
AB  - Six common health problems prevalent in two rural communities-Buoye and Kanyawegi
      Sublocations--of Kisumu District, in Western Kenya, were selected and the
      knowledge, attitudes and practices (KAP) of the communities investigated with
      special reference to human intestinal helminths (worms). The selected diseases
      were malaria, diarrhoea, human intestinal helminths, scabies, schistosomiasis,
      and measles. The selection of the six health problems was based on a previous
      more general KAP study of health and disease at household level in the two areas
      and information from the Medical Officer of Health in the area. The specific
      objective was to assess the perceived importance of intestinal worms vis-a-vis
      other common and known health problems in the community. The study included an
      analysis of responses to questions on human intestinal worms broken down by sex,
      age and education level of respondents as well as identification and perceived
      health effects of a set of vectors and parasites of common diseases in the area.
      Compared with the other five health problems, intestinal worms did not rank
      highly in people's minds as an important health problem, although very high
      proportions of respondents knew of the problem, notably the young and educated.
      This high proportion of respondents who knew of the problem could describe the
      symptoms with some accuracy and could correctly identify the vectors and parasite
      samples. But the full implications of intestinal worms were not fully
      appreciated. Both communities reflected relatively poor comprehension of causes,
      treatment and methods of prevention.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8261968
TI  - Surgical management of duodenal obstruction in older children in Kaduna, Nigeria.
AB  - Twenty children, aged between six years and fourteen years were seen and treated
      for duodenal obstruction at the Department of Surgery, Ahmadu Bello University
      Teaching Hospital, Kaduna, Nigeria, between 1st January 1990 and 31st December,
      1990. Both extrinsic and intrinsic factors caused the duodenal obstruction. All
      the patients were surgically treated and all survived. The main presenting
      clinical features, diagnosis and treatment are discussed. Follow up on some of
      the patients has been erratic because of patients defaulting on clinic
      appointments. In spite of successful surgical treatment and relief of symptoms,
      growth retardation, as shown by height and weight measurements, persisted
      relatively in patients in whom it was present at the time of diagnosis and
      treatment.

PMID- 8261969
TI  - Childhood appendicitis in Zaria: a retrospective study.
AB  - Very little had been reported about childhood appendicitis from Africa. This
      retrospective report comprises two parts. One part is an overview of appendicitis
      in 207 children operated upon between January, 1981 and December, 1990 and the
      other involved a detailed study of 44 patients seen in the last 2 years of that
      decade. Overall, there were 135 males and 72 females, aged 4 years and younger
      than 15 years. 78 children were operated upon between 1989 and 1990 and only the
      records of 44 patients had detailed enough information for inclusion in this
      study. The common symptoms of appendicitis in children were: vague abdominal
      pain, vomiting, constipation and fever. The common signs were high grade pyrexia,
      dehydration, generalized or localized abdominal tenderness. In the larger group,
      105 patients presented with perforation, 47 with gangrene, only 26.6% presented
      with uncomplicated appendicitis. In the smaller group 45.5% presented with
      perforation, 8 patients had wound infection. Four patients died; giving a
      mortality of 9%.

PMID- 8261970
TI  - Cholecystectomy with and without drainage: a prospective randomised study.
AB  - The use of subhepatic intraperitoneal drains was prospectively studied in 100
      patients who underwent elective cholecystectomy for symptomatic gallstones. These
      patients were randomised to have subhepatic drains (group A, n = 50 patients) or
      to have no drains (group B, n = 50 patients). There was no difference in the age
      or sex composition of the two groups. The patients were followed in the post
      operative period (0-7 days) for evidence of fever, wound infection, septicaemia
      and any evidence of intra-peritoneal bile leakage. Also post operative hospital
      stay of patients was noted. In group A, 14 patients (28%) developed spikes of
      temperature of 38 degrees C or more while only 5 patients (10%) in group B
      developed such episodes. The difference was statistically significant between the
      two groups (P < 0.05). Wound infection occurred significantly more (P < 0.05) in
      group A (in 15 patients) as compared to group B (in 5 patients). Septicaemia
      occurred in 2 patients in group A and in none in group B. There was no evidence
      of intraperitoneal bile leakage in either group. Patients in group A tended to
      have longer post operative hospital stay (mean of 10.2 days) than patients in
      group B (mean 8.7 days); but the difference between the two groups in this
      respect was not significant. We conclude that subhepatic intra-peritoneal drains
      offered no additional advantage in elective cholecystectomy. The evidence we had
      pointed to their harmful effects.

PMID- 8261971
TI  - Postoperative pain and analgesic prescription in Khartoum: evaluation of current
      practice.
AB  - Ninety eight general surgical patients were studied prospectively to determine
      the degree and severity of postoperative pain during the first 18 hrs following
      surgery. In 93% of the patients there was some degree of postoperative pain and
      in 64.4% the pain was moderate, severe or intolerable. Only 64.2% of the patients
      complained of pain to the medical staff, the remainder kept silent despite their
      sufferings. Pethidine was the most commonly administered analgesic and the dose
      per patient was 1.2. More diligent approach to the problem of postoperative pain
      is needed. Adequate dosage and more frequent administrations of analgesic should
      be given to post-operative patients. Moreover, patients need to be taught that
      intolerable pain is not an acceptable postoperative sequelae in exchange for
      cure.

PMID- 8261973
TI  - In vitro evaluation of carbamazepine 200 mg tablets.
AB  - A comparative in-vitro performance of carbamazepine 200mg tablet products
      available on the Kenyan market was evaluated. The products which include the
      innovator product, Tegretol, have similar quality consonant with pharmacopoeial
      specifications. A batch of one of the products had a carbamazepine content of
      106.6% label claim which was outside the upper limits of 105%. One product
      packaged in multiple-unit containers of a 1000, had an unacceptable high
      friability of 6.82% loss in weight. All products had good dissolution profiles
      and released at least 70% of the dose within 45 minutes. Drug dissolution from
      tablets was found to vary between batches for one product. At each sampling time,
      most generics had wide variations in amount of dissolved drug. The effect of such
      variations on tablet efficacy cannot be ascertained in the absence of
      bioavailability data.

PMID- 8261972
TI  - HIV infection among patients with acute pelvic inflammatory disease at the
      Kenyatta National Hospital, Nairobi, Kenya.
AB  - AIDS continues to exert considerable strain on the economy, as well as social
      aspects of our lives. Previous studies have identified the categories of people
      most at risk of contracting and developing HIV infection and AIDS. In this study,
      20.9% of women with acute pelvic infection at the Kenyatta National Hospital,
      were found to be seropositive for HIV, much higher than the general population in
      Kenya. Though there was no direct correlation between one's age and serological
      status, most of the women with pelvic inflammatory disease (PID) were young,
      quite sexually active, and involved with several partners. 49.0% of the entire
      group and 53.7% of the women who were seropositive, were married. This underlines
      the fact that marital status does not appear to offer any protection against HIV
      infection. The fact that majority of these women had started coitus quite early,
      they were not using any protective measure against STDs or HIV infection, and
      that they were involved with several partners, indicate that we are very far from
      winning the fight against HIV infection and AIDS. There is need to revise the
      currently operative programmes with a view to making them more effective, in
      preventing transmission and spread of HIV infection.

PMID- 8261974
TI  - The rate of sickness absenteeism among employees at King Khalid University
      Hospital, Riyadh, Saudi Arabia.
AB  - Sickness absence records were reviewed for all employees of King Khalid
      University Hospital, Riyadh, Saudi Arabia over a 3 year period from 1989 to 1991.
      The result showed a sickness absence rate of 7.7% with an average of 0.24 spells
      of sickness and duration of 1.24 days per absentee per year. The biological
      characteristics of the absentees showed no differentials in the spell rate of
      sickness, but nurses and junior workers had higher duration of sickness absence
      than other categories of workers. Acute respiratory and upper tract infections,
      sore throat, chickenpox, septicaemia, and diseases of the musculoskeletal system
      (mainly back pain) were the leading conditions resulting in absenteeism. This
      study revealed the need to improve the sickness absence records of the hospital
      to make it a valuable source of information for the management.

PMID- 8261975
TI  - Is periodontal disease on the increase in Kenya? A review.
AB  - During a recent scientific meeting held in Botswana (16th-19th October 1991), it
      was reported that the oral health situation in developing countries was typified
      by an increase in the prevalence of dental diseases. Kenya was cited as one of
      the typical examples of this worrying trend. For there to be an increase in
      dental diseases, there must be a concomitant increase or an upward shift in the
      main aetiological factor(s) or factors associated with dental diseases. This
      paper looks at these factors in relation to periodontal disease and reviews some
      of the major prevalence studies of periodontal disease that have been carried out
      in Kenya. It also presents some arguments to show that there is no unequivocal
      evidence that periodontal disease is on the increase in Kenya.

PMID- 8261976
TI  - Urethral calculi: a review.
AB  - The diagnosis and management of 19 patients treated for urethral calculi over a
      16-year period are reviewed. All were males, had a median age of 20 years, and
      urinary retention was the most common presenting symptom. Thirteen (68%) had
      anterior urethral calculi; 14 (74%) had anatomic alterations of the urethra; and
      12 (80%) of the patients who had urine culture had urinary infection. External
      urethrotomy and open cystolithotomy were the methods used for the removal of
      calculi in most instances.

PMID- 8261977
TI  - Paroxysmal cold haemoglobinuria coexisting with cold agglutinins in a patient
      with syphilis resulting in peripheral gangrene: a case report.
AB  - Cold-reactive antibodies may cause peripheral ischaemia, occasionally proceeding
      to gangrene on exposure to cold. A 46-year-old male with syphilis, presented with
      an unusual combination of both paroxysmal cold haemoglobinuria and cold
      agglutinin disease, resulting in peripheral gangrene and requiring bilateral
      below knee amputations.

PMID- 8261979
TI  - Pan proximal migration of ureteral stent: case report.
AB  - The upward migration of double J stent is rare. We recently had the opportunity
      to study one case with complete proximal migration of "double coil" JJ stent, a
      situation not previously described to our knowledge.

PMID- 8261978
TI  - Twice-failed tubal ligation: a case report.
AB  - The case is presented of a twice-failed tubal ligation in a woman with six
      previous children. The first failure followed laparoscopic tubal occlusion by
      silastic falope rings, while the second failure was subsequent to tubal ligation
      and division via minilaparotomy. No similar reports have been reported in the
      East African Literature. Possible reasons for failure are discussed.

PMID- 8261980
TI  - Recruitment of alpha and gamma-motoneurons in rats, dogs and humans.
AB  - 1. Single fibre action potentials were recorded with 2 pairs of wire electrodes
      from human and dog lower sacral nerve roots and the rat nervus suralis. From the
      widths of single peaks of alpha 1 (FF), alpha 2 (FR), alpha 3 (S) (extrafusal)
      and gamma 1 and gamma 21-motoneurons (intrafusal) conduction velocity frequency
      distribution histograms were constructed and the limits of the velocity ranges
      determined. Distribution changes of conduction velocities in each group of alpha
      and gamma-motoneurons were used for recruitment analysis in the occasional firing
      mode. 2. In the dog, the rat and the human, the slower conducting fibres were
      recruited before the faster conducting ones in each group of motoneurons. In the
      dog, the slowly conducting gamma 1 and alpha 2-motoneurons were recruited
      directly following bladder catheter pulling, and the slowly conducting alpha 3
      motoneurons were recruited 1 sec later. In the rat, the slowly conducting alpha 1
      motoneurons were recruited directly following pin-pricking of the hindlimb, the
      slowly conducting alpha 2-motoneurons 0.2 sec later, and the slowly conducting
      alpha 3-motoneurons 1 sec later. In humans, the slowly conducting gamma 1 and
      alpha 2-motoneurons were recruited 2 sec following bladder catheter pulling, the
      slowly conducting alpha 3-motoneurons 4 sec following pulling. 3. In the dog,
      with no additional stimulation slowly (and fast) conducting gamma 21 and alpha 3
      motoneurons showed repeated activation 3 to 4 sec later. A subgroup of the alpha
      1-motoneurons showed repeated activation every 2 sec. In the rat, without
      stimulation, a slower conducting subgroup of the alpha 1-motoneurons showed
      preferential activation of the low and high conduction velocities every 2 sec. In
      the human, with no additional stimulation, the slowly and fast conducting alpha 2
      and alpha 3-motoneurons were recruited repeatedly every 2 sec.

PMID- 8261981
TI  - Recruitment of motoneurons in the occasional firing mode in paraplegics.
AB  - 1. Single-fibre action potentials were recorded from lower sacral nerve roots of
      two humans with thoracical spinal cord lesions. Conduction velocities were
      calculated, distribution histograms of representative conduction velocity
      frequencies constructed, and recruitment of motoneurons in the different groups
      was measured. 2. Following anal and bladder catheter pulling, slowly conducting
      gamma 1, alpha 3, alpha 2 and alpha 1-motoneurons were recruited before the
      faster conducting motoneurons in each group separately. Motoneurons were
      recruited repeatedly at approx. every 2.5 sec. 3. The slowly conducting alpha 2
      motoneurons (FR) were recruited approx. 1 sec following stimulation, the slowly
      conducting alpha 3-motoneurons (S) were mostly recruited following stimulation.
      4. Upon no additional stimulation, slowly and fast conducting motoneurons were
      recruited repeatedly within the groups of alpha 2 and alpha 3-motoneurons every
      2.5 sec. 5. The faster recruitment of alpha 3-motoneurons in comparison to alpha
      2-motoneurons differed from that observed during measurements in brain-dead
      humans and in rats and dogs, and is discussed with respect to the loss of
      interneurons in the spinal cord.

PMID- 8261982
TI  - Spinal oscillators in man under normal and pathologic conditions.
AB  - 1. Single-fibre action potentials (APs) were recorded from lower sacral nerve
      roots of brain-dead humans (HTs) and two paraplegics with thoracical spinal cord
      lesions. Impulse patterns of single oscillatory firing alpha 2 and alpha 3
      motoneurons were identified and analysed. An alpha 2-motoneuron fired typically
      with 3 AP impulse trains every 160 msec. 2. In stable spinal oscillators of HTs
      the oscillation period was 70 msec plus 30 msec times the number of APs per
      impulse train; the respective values in paraplegics were 35 msec plus 40 msec
      times the number of APs per impulse train. These linear relationships indicate
      that spinal oscillators consist of at least 2 kinds of nerve cells. 3. Successive
      interspike intervals (IIs) of the impulse trains increased from about 3.5 msec to
      over 10 msec in paraplegics similarly as was the case in HTs. 4. The
      distributions of the first IIs (of impulse trains) and of the oscillation period
      of unstable continuously oscillatory firing alpha 2-motoneuron showed similar
      peaks. By relating the peak values of the first II and the oscillation period, a
      shortest II of 3.5 msec was obtained in a HT and a paraplegic, and a shortest
      oscillation period of 70 msec was measured in a HT and 40 msec in a paraplegic.
      The derivation of the shortest II of 3.5 msec from the oscillation itself is
      taken as an indication for alpha 2-motoneurons being included in the spinal
      oscillator function, since the shortest soma-dendritic spike intervals of
      motoneurons is expected to be 3.5 msec. 5. The spinal oscillator of a paraplegic
      showed more and higher activity changes than that in a HT as if spinal
      oscillators in paraplegics were insufficiently damped. 6. By interpreting the
      peaks in oscillation period distributions of unstable oscillators as being
      different oscillation loop pathways, it is speculated that the oscillators
      consist of the motoneuron, to which different interneuron pathways are connected.
      A contrasting of pathways with increasing excitation of the oscillator was
      observed. 7. The comparison of possible loop pathways of oscillation between
      paraplegics and HTs (closer to normal) indicates that the loss of descending
      tracts in paraplegics and the adaptation to it result in an increase of the
      oscillation pathways for alpha 2-oscillators from 1 to 3 in HTs to up to 6 in
      paraplegics. 8. Different measured and theoretically predictable spinal alpha 2
      oscillators can cover altogether a frequency range between 5 and 10 Hz.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8261983
TI  - Recovery functions of short and long latency reflexes in hand muscles evoked by
      paired stimulation of peripheral nerves.
AB  - Double-shock bifocal peripheral nerves stimulation with varying interstimulus
      intervals (ISI) from 1 ms to 5000 ms was applied to healthy human subjects. Short
      (SLRs) and long latency reflexes (LLRs) from the slightly active first
      interosseus dorsalis muscle were recorded after an electrical conditioning
      stimulation of the index finger and test stimulation of the median nerve. It was
      found that with intervals from 1 to 5 ms the size of the SLR and LLRs after the
      second shock was unstable and almost oscillated around that evoked by a single
      shock, possibly due to transmitter depletion at these short ISIs. With intervals
      of 10 ms and longer, the test responses progressively increased: the SLR to 100
      ms ISI, the LLR1 to 500 ms ISI and the LLR2 to 2000 ms ISI, probably due to
      temporal summation and some release of the transmitter substance after the
      conditioning cutaneous stimulus. All the recovery curves fully returned to the
      control value at 2000 ms and 3000 ms ISI, respectively. The main result is that
      cutaneous conditioning stimulation is not able to reduce or even to block the
      test SLR and LLRs. Interference phenomena did not occur between different
      afferents when paired stimulation was applied bifocally as the conditioning input
      in respect to a test nerve volley, was very limited. On the contrary, the test
      responses were far larger than the control response, probably due to some
      temporal summation with double-shock stimulation and because of the enhanced
      spinal excitability during slight voluntary contraction.

PMID- 8261984
TI  - Autonomic system dysfunction in moderate diabetic polyneuropathy assessed by
      sympathetic skin response and Valsalva index.
AB  - 30 patients with moderate diabetic polyneuropathy (Stage 2 according to Dyck)
      were evaluated for autonomic symptoms, sympathetic skin response (SSR) and
      Valsalva index. Their SSR were compared to a control group of 30 healthy normal
      subjects. Neuropathy was confirmed by history, clinical examination and nerve
      conduction measurements. Although our patients had only moderate polyneuropathy
      autonomic dysfunction was frequent. Two thirds reported autonomic symptoms.
      Impotence was present in 60% of males. SSR amplitudes were significantly lower in
      diabetics (changed in 53%, absent in 20%) than in the controls. SSR abnormality
      correlated to some clinical and electroneurographic signs of neuropathy,
      suggesting similar affection of sympathetic and somatic fibres. Valsalva index
      was abnormal in 37% of patients showing no correlation to clinical,
      electroneurographic or SSR changes.

PMID- 8261985
TI  - F-wave characteristics following acute and chronic upper motor neuron lesions.
AB  - F-waves were analyzed in 40 patients shortly following the onset of moderate to
      severe flaccid hemiparesis due to hemispheric strokes. The test was repeated in
      25 patients three or more months later. F-waves were recorded following trains of
      20 stimuli from the ulnar and common peroneal nerves bilaterally. The
      persistence, minimal, maximal and average latencies, durations, amplitudes and
      areas of these waves were determined. Acutely, several F-wave parameters
      (persistence, maximal and average duration, amplitude and area) were
      significantly reduced on the paretic side. Changes were slightly more pronounced
      in patients with more severe weakness and flaccidity. In the chronic phase, the
      average F-wave amplitude and area values on the paretic side increased, becoming
      similar to or larger than on the normal side. However, the correlation with
      muscle strength and tone changes was poor.

PMID- 8261986
TI  - Endoscopic resection of early gastric cancer.

PMID- 8261987
TI  - Endoscopic laser treatment for early gastric cancer.
AB  - Endoscopic laser treatment (ELT) has been proposed as one of the curative
      endoscopic therapies for early gastric cancer. We report our experience with ELT
      in 111 patients with early gastric cancer limited to the mucosa as diagnosed by
      endoscopy and/or endoscopic ultrasonography. Twelve patients subsequently
      underwent laparotomy after ELT and no residual tumor was found in 75% of these
      cases. Ninety-nine patients had no surgery for various reasons and follow-up
      information by endoscopy was available for 73 of them for a mean of 2.7 years
      (range 1 to 7 years). 81% of these patients were found to be tumor free. There
      was no difference in the success rate of ELT in relation to endoscopic
      classification, tumor location and histologic type of cancer. Recently, the
      indications for ELT decreased due to the development of endoscopic mucosal
      resection (EMR) enabling histological evaluation of a resection specimen.
      However, the technique of EMR cannot always be performed completely depending on
      the location and size of the lesions. Therefore, we employed ELT as an additional
      treatment technique after EMR therapy to achieve complete tumor destruction.
      Results in 13 patients where both techniques were employed showed complete tumor
      removal in 11 cases. At present, this combined application may be the most
      important role of laser irradiation for the treatment of early stage GI tract
      malignancies.

PMID- 8261988
TI  - Endoscopic mucosal resection of flat and depressed types of early colorectal
      cancer.

PMID- 8261989
TI  - Laser ablation of early colorectal malignancy.
AB  - Between November 1979 and July 1992, 35 patients with early colon cancer were
      treated with a non-contact, high power Nd: YAG CW laser. Criteria for
      classification as early colon cancer were the presence of adenocarcinoma in deep
      biopsies of flat tissue or within and underneath the polypectomy resection
      margin, and evidence on endosonography of infiltration into but not beyond the
      submucosal layer without evidence of lymph node involvement. Fifteen patients
      fulfilled both requirements, another 15 had been treated in the presonographic
      period, and 5 had abnormal endosonographic findings but inconclusive biopsies.
      Laser treatment was evaluable in 30 patients. Complete eradication was achieved
      in 28 patients, after a median of two treatments given over a median period of 42
      days without complications. No recurrence was seen in a median follow-up period
      of three years. The cumulative probability of survival at one, two and five years
      was 94%, 84% and 62%, respectively, in an elderly and medically compromised
      patient group (median age 74 years). As complete, fast and safe eradication is
      possible in over 90% of cases, curative laser treatment should be considered in
      highly selected cases with limited wall invasion, as established at
      endosonography.

PMID- 8261990
TI  - The rationale for current practice in the management of malignant colonic polyps.

PMID- 8261991
TI  - Echoendoscopy prior to endoscopic tumor therapy--more safety?
AB  - Echoendoscopy has been found useful to better define gastrointestinal tract
      tumors which may be suitable for endoscopic treatment. In benign tumors,
      echoendoscopy may be used to decrease the risk of hemorrhage or perforation
      before resection of large polyps or submucosal lesions. The most important
      indications for echoendoscopy, however, are in the field of GI oncology, and the
      method may lead to a better selection of superficial cancers without lymph node
      metastases. However, endoscopic ultrasound is still limited in differentiating
      mucosal from submucosal tumors and in the detection and interpretation of small
      lymph nodes. Technical improvements and careful interpretation of echoendoscopy
      will increase the number of patients cured by non-surgical procedures in the
      future.

PMID- 8261992
TI  - Endoscopic resection of gastrointestinal tumors.

PMID- 8261993
TI  - Esophageal ulcer caused by atypical mycobacteria: a case report.

PMID- 8261994
TI  - Adult duodenal web: endoscopic management.

PMID- 8261995
TI  - Esophageal tuberculosis: early diagnosis by endoscopy.

PMID- 8261996
TI  - Mallory-Weiss tear after pneumatic dilatation in achalasia.

PMID- 8261997
TI  - Salmonellosis-induced hemorrhage and ulcerations of the colon.

PMID- 8261998
TI  - Diagnosis of giardiasis: possible role of ileal biopsy smear.

PMID- 8261999
TI  - Double-duct-sign--is it always cancer?

PMID- 8262000
TI  - Endoscopic diagnosis and extraction of gastric parasites.

PMID- 8262001
TI  - Kinking of splenic artery mimicking gastric leiomyoma.

PMID- 8262002
TI  - Papillomas of the esophagus: report on nine cases.

PMID- 8262003
TI  - Burkitt's lymphoma of the stomach: a case presenting with a submucosal tumor and
      coffee-cup-like ulcers.

PMID- 8262004
TI  - Mandatory neuropeptide-steroid signaling for the preovulatory luteinizing hormone
      releasing hormone discharge.
AB  - In this article I have examined various aspects of the complex spatio-temporal
      patterning of peptidergic signaling that lead to synchronized development of
      neural events for the preovulatory LHRH discharge on proestrus. Undoubtedly, the
      integration of these events is orchestrated by both ovarian steroids, E2 and P.
      Evidence accumulated in recent years has failed to affirm the perceived notion
      that E2 is an adequate peripheral signal for the timely, robust discharge of LHRH
      on proestrus. The current understanding is shaped by the thesis that the
      concerted central actions of E2 and P are mediated by a host of regulatory
      peptides produced locally in the hypothalamus, and steroids, in general, augment
      the production and release of both inhibitory and excitatory peptides in a timely
      fashion to facilitate the preovulatory LHRH discharge. Since these peptidergic
      pathways appear mandatory for signal transfer, considerable recent research has
      been devoted first to identifying the signals that selectively participate in the
      induction of preovulatory LHRH (LH) surge, and then to trace the route of signal
      transmission that ultimately leads to LHRH hypersecretion on the afternoon of
      proestrus (Fig. 1). The peptidergic pathways that propagate and transmit impulses
      for the preovulatory LHRH discharge reside in the SCN-MPN-MPOA-ARC-ME neural
      complex (Fig. 1). The timely initiation of these impulses is entrained to the
      photo-periodic input reaching the SCN by the retino-hypothalamic tract. The
      evidence is already in place to show that further information processing is
      transduced in the MPN; however, the nature of neurochemical signaling between the
      two sites remains to be deciphered. The available evidence favors a mandatory
      participation of inhibitory (EOP and NPK) and excitatory (NPY, GAL, NT, and AII)
      messenger molecules within the SCN-MPN-MPOA-ARC-ME complex (Fig. 1). It is
      possible that the relevant information from the SCN-MPN is conveyed caudally to
      the ARC in order to initiate a chain of events for disinhibition/excitation of
      the NPY-EOP network and to affect LHRH neurosecretion at the perikaryal level in
      the MPOA and at axon terminals in the ME. Also, either concurrently or on a time
      delayed basis, the relevant information from the MPN may be relayed to the MPOA
      via the local peptidergic network comprised of NT, EOP, NPK, and GAL. This
      transmission may initially be critical for elicitation of antecedent
      neurosecretory events in the ME and to ultimately evoke the preovulatory LHRH
      surge.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8262005
TI  - Immunoendocrine communication via the hypothalamo-pituitary-adrenal axis in
      autoimmune diseases.

PMID- 8262006
TI  - alpha-Melanocyte stimulating hormone in the modulation of host reactions.

PMID- 8262007
TI  - Steroid 5 alpha-reductase 2 deficiency.
AB  - In the 20 yr since it was established that impairment of dihydrotestosterone
      formation is the cause of a rare form of human intersex, a wealth of information
      has accumulated about the genetics, endocrinology, and variable phenotypic
      manifestations, culminating in the cloning of cDNAs encoding two 5 alpha
      reductase genes and documentation that mutations in the steroid 5 alpha-reductase
      2 gene are the cause of 5 alpha-reductase deficiency. Perplexing and difficult
      problems remain unresolved, e.g. whether the variability in manifestations is due
      to variable expressions of steroid 5 alpha-reductase 1 or to effects of
      testosterone itself. It is also imperative to establish whether defects in
      steroid 5 alpha-reductase 2, perhaps in the heterozygous state, are responsible
      for a portion of cases of sporadic hypospadias, to determine whether 5 alpha
      reductase plays a role in progesterone action in women, and to elucidate the
      relation between androgen action and gender role behavior.

PMID- 8262008
TI  - Circadian rhythms during pregnancy.

PMID- 8262009
TI  - The inositol phosphate-calcium signaling system in nonexcitable cells.

PMID- 8262010
TI  - The ways in which hormones change cyclic adenosine 3',5'-monophosphate-dependent
      protein kinase subunits, and how such changes affect cell behavior.
AB  - Hormones and cytokines regulate many cellular functions by activating the
      ubiquitous cAMP-dependent protein kinase (A kinase) system. Newly synthesized
      cAMP molecules bind to regulatory (R) subunits in A kinase holoenzymes, causing
      them to release their catalytic (C) subunits. These free C subunits then
      phosphorylate proteins until the cAMP level falls, whereupon the R subunits
      regain their affinity for free C subunits, and thus form inactive holoenzymes
      again. However if cAMP levels remain persistently elevated, many cells change
      their A kinase system. Some cells alter the rate of degradation of subunits, and
      some cells change the level or stability of the messages encoding subunits.
      Cellular behavior often changes if cAMP levels remain elevated: many cells
      differentiate, some cells proliferate, and some cells die, depending on the stage
      of the cell cycle. The two forms of A kinase holoenzyme (type I and type II)
      contain identical C subunits, but contain either an RI dimer or an RII dimer. In
      some tissues, type II holoenzyme is compartmentalized to subcellular organelles
      via specific anchoring proteins, whereas type I holoenzyme is generally
      cytosolic. Free RI subunits turn over more rapidly than free RII subunits in most
      cells, but all free subunits are degraded more rapidly than when they are
      associated together in holoenzymes. Free C subunits can phosphorylate a broad
      spectrum of proteins in both the cytoplasm and nucleus, depending on the type of
      cell, its state of differentiation, and the hormonal milieux. If free C subunit
      is microinjected into the cytoplasm of some intact cells, it migrates to the
      nucleus, whereas if free R subunit is microinjected, it remains in the cytoplasm.
      If both subunits are coinjected, R subunit blocks the nuclear migration of the C
      subunit. A major nuclear target for free C subunits is the CREB family of nuclear
      proteins, which bind to cAMP response elements (CREs) in the promoter regions of
      cAMP-responsive genes. Phosphorylation of CREB proteins alters their ability to
      form dimers and to interact with CREs. Many CREB proteins can be phosphorylated
      by other kinases as well, indicating this is one means by which cells coordinate
      cAMP- and non-cAMP-mediated gene responses. However, interactions between CREB
      and a number of other nuclear proteins with which they can dimerize, especially
      proteins whose levels are rapidly altered in response to hormones, provide an
      even higher degree of complexity of gene regulation than is possible from various
      kinases phosphorylating the different sites in CREB proteins.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8262011
TI  - Nuclear receptor/AP-1 interaction.

PMID- 8262012
TI  - Overview of validity, quality control and measurement error issues in nutritional
      epidemiology.

PMID- 8262013
TI  - Minimizing error in the field: quality control in dietary surveys.

PMID- 8262014
TI  - Measurement error in alcohol consumption: the Swiss Health Survey.
AB  - It is planned to include in the Swiss Health Survey (SHS) the questions on the
      consumption of alcohol that have been part of the Trend Surveys of the Swiss
      Institute for the Prevention of Alcohol and Drug Problems (SIPA). Since both
      surveys use different questioning methods (SHS: telephone interview/self
      administered questionnaire; SIPA Trend Surveys: personal interviews) a
      comparative study was carried out to test possible effects of the methods used on
      responses about alcohol consumption. A split-sample design was used, whereby 1097
      persons were asked about their alcohol intake by personal interview, and 1154
      persons completed a self-administered questionnaire with the same questions.
      Considerable differences were found: on an average, consumption reported by
      personal interview was 38.5% higher among males (including abstainers: 35.9%) and
      18.0% higher among females (including abstainers: 17.4%) than that reported by
      self-administered questionnaire. Consumption figures as assessed by personal
      interview correspond better to the per capita consumption figures as estimated by
      sales. Preliminary conclusions concerning the design of future surveys of alcohol
      consumption in Switzerland are presented.

PMID- 8262015
TI  - Correction for measurement error.

PMID- 8262016
TI  - The analysis of case-control studies under validation subsampling.
AB  - In case-control studies, one often finds that covariates are missing or measured
      with error in the entire sample, whereas complete or exact covariate information
      is available only in a subsample. This paper discusses the analysis of case
      control studies under a double-sampling scheme, where at the first stage
      covariates are measured with error or missing, and at the second stage are
      validated in a subsample. The method proposed combines the risk information from
      both samples by assuming that (1) the disease incidence model is logistic, (2)
      the partial or proxy information takes on finitely many values, and (3) the error
      is non-differential. The estimator is obtained by jointly fitting logistic models
      to the first and second stage data, a variance formula is presented. Parameters
      can be estimated by use of standard packages for dose-response data. Data from an
      ongoing case-control study on lung cancer serve as an example.

PMID- 8262017
TI  - Remarks on the use of Pearson's correlation coefficient and other association
      measures in assessing validity and reliability of dietary assessment methods.

PMID- 8262018
TI  - Controlling for total energy intake in regression models for assessing
      macronutrient effects on disease.
AB  - This paper illustrates the relationships between the (i) the standard
      multivariate method, (ii) the energy-adjusted method and (iii) the energy
      decomposition method for controlling for total energy intake. The setting is a
      general regression model which includes linear, logistic and Cox regressions. The
      discussion is confined to effects of macronutrients and to situations in which
      total energy intake is associated with disease. Pike, Bernstein & Peters [(1989)
      Am. J. Epidemiol. 129, 1312-1313] show how the three methods relate to each other
      and that the choice between them is a matter of taste. Here the relationships are
      illustrated using Venn-type diagrams. However, the rationale for all current
      controlling procedures relies on the assumption of external factors acting
      uniformly over different sources of energy. This assumption should be challenged.
      Furthermore, if individual macronutrients have independent, possibly even
      opposite effects on the risk for disease, then adjustment of any one of them will
      be relative to the effect of the others. This might not be satisfactory. Current
      methodology does not resolve these problems, and more elaborate data as well as
      further thought is needed.

PMID- 8262019
TI  - Adjustment for total caloric intake in nutritional studies: an epidemiological
      perspective.

PMID- 8262020
TI  - Recommendations for the design and analysis of nutritional epidemiologic studies
      with measurement errors in the exposure variables. From the BGA Commission on
      Nutritional Epidemiology.

PMID- 8262021
TI  - Biomarkers for validation.

PMID- 8262022
TI  - Cognitive psychological issues of relevance to the validity of dietary reports.
AB  - All dietary assessment methods engage the cognitive processes of respondents,
      requiring them to retrieve and report information from memory. I first discuss
      the distinction between daily and frequency methods of dietary assessment: from a
      psychological perspective, the essential distinction between these classes of
      methods is in the cues that are provided for retrieval of information rather than
      the length of the reference period or the specificity of the information to be
      retrieved. I then review selectively psychological research on aspects of
      cognition that are central to dietary reporting; chief among these are the nature
      of the representation of dietary information in memory and the fidelity of
      frequency judgments. I conclude by describing several potential areas for
      collaborative research between cognitive psychologists and nutritional
      epidemiologists. The ability of respondents to provide data must be considered in
      the design and selection of dietary assessment methods.

PMID- 8262023
TI  - EURAMIC Study: antioxidants, myocardial infarction and breast cancer. Design and
      main hypotheses.
AB  - Epidemiological studies have not given sufficient evidence yet for the role of
      antioxidant nutrients in the prevention of cardiovascular disease. As regards
      cancer, an inverse association between beta-carotene intake and specific types of
      cancer, especially lung cancer, has been shown. For other cancer sites and other
      antioxidants, the association is less clear. The EURAMIC Study, an EC Concerted
      Action, is a case-control study conducted in 11 countries, in which the combined
      effect of vitamin E, beta-carotene and selenium, in relation to fatty acid
      intake, will be examined. The disease endpoints are acute myocardial infarction
      and early-stage breast cancer. The broad range of antioxidant intake, the use of
      biomarkers of exposure, and the analysis of pooled data will allow an estimate of
      the strength of the putative beneficial effect. In this paper the background and
      design of the study will be introduced.

PMID- 8262024
TI  - Food components and mechanisms of interest in cancer and diet in relation to
      their measurement.

PMID- 8262025
TI  - Knowledge and strategies in diagnostic skill.
AB  - A theoretical framework for diagnosis in technical environments is presented,
      consisting of three layers. At the first layer, the task structure, top-level
      goals of the diagnostic tasks are identified that have to be fulfilled during
      task execution. This task structure may also be viewed as a global strategy to
      carry out the diagnostic task. The second layer of knowledge consists of the
      relevant local strategies by means of which values are obtained for goals in the
      task structure. The third layer consists of underlying domain knowledge. This
      theoretical framework is used to interpret the results as presented in the
      literature on diagnosis in technical environments. Finally, based on this
      framework, recommendations are made with respect to the training of diagnostic
      skill.

PMID- 8262026
TI  - Diagnostic orientation in control of disturbance situations.
AB  - The object of the study is diagnostic judgement in the control of dynamic
      processes. The starting point was the known difficulty process operators have in
      utilizing knowledge of process dynamics in disturbance situations that require
      both diagnostic and prognostic actions. A model of the diagnostic judgement
      process as a construction of coherent interpretation of the situation is
      outlined, and comprehensive data from simulated disturbance handling by six crews
      of a PWR type nuclear power plant, was analysed. The phases of analysis included
      evaluation of the adequacy of task performance, utilization of available process
      information, and evaluation of the interpretation of disturbance situations. The
      results suggest that a functional orientation towards task performance allows a
      more coherent and comprehensive interpretation of the situation and more adequate
      task performance. Coherence of interpretation seems to be reflected in a higher
      subjective certainty compared with crews with an incoherent interpretation.

PMID- 8262027
TI  - Analysing communication in complex distributed decision-making.
AB  - This paper analyses emergency tasks within the theoretical framework of dynamic
      environment management with distributed decision-making (DDM). Models of task and
      work organization are used to analyse verbal exchanges in order to infer
      collective strategies. A cross-analysis method serves to analyse communication
      from the standpoint of both semantics and structure of the exchanges. The
      findings of two empirical comparative studies show that invariants vs differences
      in the organization and the semantics of exchanges are associated with invariants
      vs differences in parameters of the situations themselves (initial state and
      final result of actions). Efficient strategies were linked with well-structured
      flow of communication and roles distribution.

PMID- 8262028
TI  - Strategic thinking and stress.
AB  - In this study we investigate the behaviour and the performance of experimental
      subjects, who had to solve a series of tasks of 'strategic thinking' under a
      stress and a non-stress condition. No significant differences between the
      conditions could be found with respect to performance and improvement of
      performance within the series of tasks, but the experimental subjects exhibited
      under the different conditions different forms of behaviour. Unexpectedly the Ss
      working under the stress-condition exhibited a more 'analytical' behaviour and
      increased their workload, instead of decreasing it. Additionally they exhibited a
      tendency for measures with salient effects and proved to be better in finding the
      right points of main effort. The results are discussed with respect to a general
      theory of action regulation.

PMID- 8262029
TI  - Analyses of cognitive processes in train traffic control.
AB  - The study of complex information processing and problem-solving situations in
      practice is discussed, in particular the methods of analysing the cognitive
      aspects in train dispatcher's work. Some parallels are drawn with related work in
      processing industries. A prerequisite for the approach to the issue was that the
      results would have to yield very concrete starting-points for the design of
      technical aids. The research started from the assumption that it would be
      extremely difficult to derive design indications from apparently observable
      actions of the train dispatchers. This led to the choice of a combination of a
      preliminary simulation study followed by analysis of cognitive processes in the
      train dispatcher's behaviour in every day practice. It turned out to be helpful
      for the analysis to draw parallels between the cognitive processes in the
      behaviour of the train dispatchers and the way of working/thinking shown by test
      subjects in complex problem-solving experiments.

PMID- 8262030
TI  - AMME: an Automatic Mental Model Evaluation to analyse user behaviour traced in a
      finite, discrete state space.
AB  - To support the human factors engineer in designing a good user interface, a
      method has been developed to analyse the empirical data of the interactive user
      behaviour traced in a finite discrete state space. The sequences of actions
      produced by the user contain valuable information about the mental model of this
      user, the individual problem solution strategies for a given task and the
      hierarchical structure of the task-subtasks relationships. The presented method,
      AMME, can analyse the action sequences and automatically generate (1) a net
      description of the task dependent model of the user, (2) a complete state
      transition matrix, and (3) various quantitative measures of the user's task
      solving process. The behavioural complexity of task-solving processes carried out
      by novices has been found to be significantly larger than the complexity of task
      solving processes carried out by experts.

PMID- 8262031
TI  - Verbal protocol accuracy in fault diagnosis.
AB  - The study examined whether concurrent and retrospective verbal protocols possess
      the potential to provide a non-reactive and valid account of the cognitive
      processes involved in fault diagnosis. With this goal in mind, a group of
      subjects performed a fault diagnosis task under concurrent and retrospective
      verbalization and in a silent control condition as well. In the task, concurrent
      verbalization led to a considerable increase in time to completion, but exerted
      no effect on overall accuracy and the adopted strategy. Retrospective
      verbalization did not have any effect on performance. The strategy-related data
      obtained under concurrent verbalization proved to be more valid than those
      obtained under retrospective verbalization. On the basis of the results it is
      suggested that, where possible, concurrent verbal reports should be collected
      when trying to get a better understanding of the nature of the fault diagnostic
      process.

PMID- 8262032
TI  - Types of hierarchy imply types of model.
AB  - The types of hierarchy that describe the knowledge structures used by people
      doing complex tasks imply that certain types of cognitive mechanism are available
      to process them. This paper will discuss principles of organization in is-a
      (classification) and part-whole hierarchies. The principles of organization may
      be different at different levels of a hierarchy. The behaviour of people doing
      complex tasks is adaptable as a function of context. These factors taken together
      imply that cognitive processing is done by independent modules working within a
      context, rather than by a sequence of processing stages, and that a sequential
      stages processing model is a special case of a more general process. The paper
      ends with some practical implications of this change in models of the cognitive
      processes underlying complex behaviour.

PMID- 8262033
TI  - Towards models of tasks and task complexity in supervisory control applications.
AB  - Dynamic task environments in supervisory control situations differ from those
      traditionally investigated in problem-solving research in that (1) several task
      goals exist in parallel, (2) task goals change dynamically as the behaviour of
      the technical process changes, and (3) information required to accomplish task
      goals changes across time. In the present work, it is suggested that such dynamic
      task environments can be described using two types of task goal networks, namely
      a control task goal (CTG) network and an information processing goal (IPG)
      network. CTG networks are generated by analysis of the operational states
      required to produce the commodity for which a technical system has been designed.
      For example, such analyses can be performed using approaches such as Mitchell's
      operator function model or canonical means-end analyses. IPG networks are
      generated by using the recently proposed functional information and knowledge
      acquisition (FIKA) modelling technique. Two examples from different domains
      illustrate how these task goals networks can be used to describe dynamic task
      environments. Finally, two different ways of using the task modelling approach
      are briefly discussed.

PMID- 8262034
TI  - Developing and using cognitive task typologies.
AB  - Based on experiences from case studies, some preliminary thoughts are presented
      regarding the why and how of developing a cognitive task typology model. Three
      different practical functions of such a typology are outlined: comparison,
      prediction, and design. These functions can be applied to sets of tasks both in
      the same and in different task worlds (e.g. artificial/laboratory tasks vs. real
      life/case study tasks). Several existing techniques may be suitable for this
      purpose: hierarchical task analysis, verbal protocols, and the use of elementary
      cognitive modules. Finally two partly overlapping approaches to identify relevant
      task dimensions for a typology are outlined: one based on a macro-ergonomic view
      of human-machine systems, and the other centred around the cognitive concept of
      an operator's mental model of the task. In the Discussion a bottom-up strategy
      for typology development is advocated, and the relationship with task complexity
      is noted.

PMID- 8262035
TI  - Ribosomal protein L6: structural evidence of gene duplication from a primitive
      RNA binding protein.
AB  - In all cells, protein synthesis is coordinated by the ribosome, a large
      ribonucleoprotein particle that is composed of > 50 distinct protein molecules
      and several large RNA molecules. Here we present the crystal structure of
      ribosomal protein L6 from the thermophilic bacterium Bacillus stearothermophilus
      solved at 2.6 A resolution. L6 contains two domains with almost identical folds,
      implying that it was created by an ancient gene duplication event. The surface of
      the molecule displays several likely sites of interaction with other components
      of the ribosome. The RNA binding sites appear to be localized in the C-terminal
      domain whereas the N-terminal domain contains the potential sites for protein
      protein interactions. The domain structure is homologous with several other
      ribosomal proteins and to a large family of eukaryotic RNA binding proteins.

PMID- 8262036
TI  - CD4 cell surface downregulation in HIV-1 Nef transgenic mice is a consequence of
      intracellular sequestration.
AB  - The Nef gene product is a regulatory protein of HIV whose biological function is
      poorly understood. Nef has been thought to have a negative effect on viral
      replication in vitro but has been shown in studies with SIV to be necessary in
      the establishment of viraemia in vivo. In vitro studies in various human cell
      lines have shown that Nef downregulates the expression of cell surface CD4 and
      thus could have effects on the immune response. We have generated four transgenic
      mouse lines, with constructs containing two different Nef alleles under the
      control of CD2 regulatory elements to examine the interaction of Nef with the
      host immune system in vivo. In adult transgenic mice we have found marked
      downregulation in the level of CD4 on the surface of double positive thymocytes
      and a decrease in the number of CD4+ T cells in the thymus. Functional analyses
      have revealed a decrease in the total activation of transgenic thymocytes by anti
      CD3 epsilon antibody. By specific intracellular staining of T cells in such mice
      we have found CD4 colocalizing with a Golgi-specific marker. These results
      strongly suggest a Nef mediated effect on developing CD4 thymocytes resulting
      from interference of Nef in the intracellular trafficking or post-translational
      modification of CD4.

PMID- 8262037
TI  - Constitutive binding of EBNA1 protein to the Epstein-Barr virus replication
      origin, oriP, with distortion of DNA structure during latent infection.
AB  - Replication of the circular, 170 kb genome of Epstein-Barr virus (EBV) during
      latent infection is performed by the cellular replication machinery under cell
      cycle control. A single viral protein, EBNA1, directs the cellular replication
      apparatus to initiate replication within the genetically defined replication
      origin, oriP, at a cluster of four EBNA1 binding sites, referred to here as the
      physical origin of bidirectional replication, or OBR. A second cluster of EBNA1
      binding sites within oriP, the 30 bp repeats, serves an essential role as a
      replication enhancer and also provides a distinct episome maintenance function
      that is unrelated to replication. We examined the functional elements of oriP for
      binding by EBNA1 and possibly other proteins in proliferating Raji cells by
      generating in vivo footprints using two reagents, dimethylsulfate (DMS) and
      KMnO4. We also employed deoxyribonuclease I (DNase I) with permeabilized cells.
      The in vivo and permeabilized cell footprints at the EBNA1 binding sites,
      particularly those obtained using DMS, gave strong evidence that all of these
      sites are bound by EBNA1 in asynchronously dividing cells. No consistent evidence
      was found to suggest binding by other proteins at any other sites within the
      functional regions of oriP. Thymines at symmetrical positions of the OBR within
      oriP were oxidized when cells were treated with permanganate, suggestive of bends
      or other distortions of DNA structure at these positions; binding of EBNA1 in
      vitro to total DNA from Raji cells induced reactivity to permanganate at
      identical positions. The simplest interpretation of the results, which were
      obtained using asynchronously dividing cells, is that EBNA1 binds to its sites at
      oriP and holds the OBR in a distorted conformation throughout most of the cell
      cycle, implying that replication is initiated by a cellular mechanism and is not
      limited by an availability of EBNA1 for binding to oriP.

PMID- 8262038
TI  - Tracing B cell development in human germinal centres by molecular analysis of
      single cells picked from histological sections.
AB  - Germinal centres are areas of intense B lymphocyte proliferation inside primary B
      cell follicles in spleen and lymph nodes. Rearranged V genes from single human B
      cells, isolated from histological sections of two such structures by
      micromanipulation, were amplified and sequenced. Cells from the follicular mantle
      were clonally diverse and largely expressed germline V genes. Germinal centres
      were dominated by a few large B cell clones dispersed throughout these structures
      and exhibiting intraclonal diversity by ongoing somatic hypermutation. Pronounced
      counterselection of replacement mutations seen in one of the germinal centres may
      indicate a late phase of the germinal centre reaction. A polyclonal population of
      activated B cells expressing unmutated antibodies in the dark zone of the other
      germinal centre may represent the initial founder cells.

PMID- 8262039
TI  - Evidence that retroviruses integrate into post-replication host DNA.
AB  - We have studied the question of whether a retrovirus integrates into the
      chromosomal DNA of the host cell before or after the DNA is replicated during the
      S phase of the cell cycle. We have infected single NIH-3T3 cells with BAG, a
      replication-incompetent retroviral vector which encodes the lacZ gene, then
      observed the clones derived from these cells to discover whether all the cells
      carry a copy of the proviral DNA. We have discovered that only half of the
      progeny of an infected cell carries a copy of the provirus. This indicates that
      the virus only integrates into post-replication DNA. We discuss the implications
      of this result for applications of retroviruses, such as gene therapy and cell
      lineage, which use them as vehicles for gene transfer into stem cells.

PMID- 8262040
TI  - Suicidal nucleotide sequences for DNA polymerization.
AB  - Studying the activity of T7 DNA polymerase (Sequenase) on open circular DNAs, we
      observed virtually complete termination within potential triplex-forming
      sequences. Mutations destroying the triplex potential of the sequences prevented
      termination, while compensatory mutations restoring triplex potential restored
      it. We hypothesize that strand displacement during DNA polymerization of double
      helical templates brings three DNA strands (duplex DNA downstream of the
      polymerase plus a displaced overhang) into close proximity, provoking triplex
      formation, which in turn prevents further DNA synthesis. Supporting this idea, we
      found that Sequenase is unable to propagate through short triple-helical
      stretches within single-stranded DNA templates. Thus, DNA polymerase, by inducing
      triplex formation at specific sequences in front of the replication fork, causes
      self-termination. Possible biological implications of such 'conformational
      suicide' are discussed. Our data also provide a novel way to target DNA
      polymerases at specific sequences using triplex-forming oligonucleotides.

PMID- 8262041
TI  - Repression of adenovirus E1A enhancer activity by a novel zinc finger-containing
      DNA-binding protein related to the GLI-Kruppel protein.
AB  - We have previously shown that expression of the E1A oncogene is negatively
      regulated in rodent fibroblast cells by a nuclear factor (phi AP3) that binds to
      the E1A promoter region just upstream of the canonical enhancer element. To
      understand how phi AP3 can regulate E1A gene transcription by inactivation of the
      enhancer function, we have used an oligonucleotide probe containing a binding
      site for this protein to clone the mouse phi AP3 gene. DNA sequence analysis of
      the 2.3 kb cDNA revealed the presence of six well-conserved zinc finger DNA
      binding motifs, which were highly related to those found in the GLI-Kruppel
      family of human zinc finger proteins. Analysis of the tissue distribution of the
      phi AP3 mRNA suggested that its expression was ubiquitous but at variable levels,
      most likely as a result of post-transcriptional regulation of mRNA stability. The
      phi AP3 factor is a nuclear phosphoprotein; the extent of its phosphorylation is
      regulated during the cell cycle. Preferential binding of the hyperphosphorylated
      form of this protein to DNA was observed. Co-expression of the phi AP3 cDNA and a
      luciferase reporter gene under the control of the E1A promoter/enhancer in
      several human cell lines resulted in repression of E1A enhancer activity. In
      contrast, when the phi AP3 binding site upstream of the enhancer was mutated, no
      inhibition of enhancer function was observed. Based on these observations we
      conclude that we have cloned the cellular phi AP3 gene, and that the DNA-binding
      activity of this protein is regulated during the cell cycle.

PMID- 8262042
TI  - The two zinc finger-like domains of GATA-1 have different DNA binding
      specificities.
AB  - The GATA-1 transcription factor has been shown to be important in the regulation
      of globin and non-globin genes in erythroid, megakaryocytic and mast cell
      lineages. It is a member of a family of GATA proteins which both overlap in their
      expression patterns and bind the motif (A/T)GATA(A/G). The GATA family of
      proteins are also members of the superfamily of zinc finger-like domain proteins
      and have two similar domains of the type Cys-X2-Cys-X17-Cys-X2-Cys which direct
      the DNA binding of the protein. A random oligonucleotide selection procedure has
      been employed to further elucidate the mechanism of GATA-1-DNA recognition. The
      resulting oligonucleotides were tested for binding activity to both wild-type and
      mutant GATA-1 proteins. Two classes of GATA-1-DNA interaction have been defined,
      the first requiring only the carboxy finger of GATA-1 to bind and having the
      motif GAT(A/T), the second requiring both finger domains to bind and having the
      core motif (T/C)AAG. By using sequence comparison and depurination analysis it is
      concluded that the two finger-like domains of GATA-1 have different DNA binding
      recognition motifs. Binding of GATA-1 to GAT(A/T) motifs is associated with
      transcriptional activation of linked genes. The only known (T/C)AAG motif is in
      the distal CAAT-box promoter region of the human A gamma-globin gene where the
      binding of GATA-1 appears to regulate the correct developmental suppression of
      gamma-globin expression.

PMID- 8262043
TI  - Identification of the C-terminal activator domain in yeast heat shock factor:
      independent control of transient and sustained transcriptional activity.
AB  - In yeast, heat shock factor (HSF) is a trimer that binds DNA constitutively but
      only supports high levels of transcription upon heat shock. The C-terminal
      regions of HSF from Saccharomyces cerevisiae and Kluyveromyces lactis are
      unconserved yet both contain strong transactivators which are correctly regulated
      when substituted for each other. We have performed high resolution mapping of
      these activator domains which shows that in K.lactis HSF (KlHSF) activity can be
      located to a confined short domain, while in S.cerevisiae HSF (ScHSF) two
      separate regions are required for full activity. Alignment of the activator
      domains reveals similarity, as both overlap potential leucine zipper motifs
      (zipper C) with a distribution of hydrophobic residues similar to two highly
      conserved N-terminal domains which mediate HSF trimerization (zippers A and B).
      In higher eukaryotes a C-terminal leucine zipper is required to maintain HSF in a
      monomeric and non DNA-binding state under normal conditions and we therefore
      address the regulatory roles of the three leucine zipper motifs in KlHSF. Whilst
      the longest and most N-terminal of the trimer region zippers, A, is dispensable
      for regulation, mutation of a single leucine in zipper B makes HSF constitutively
      active. In contrast to the situation in higher eukaryotes disruption of zipper C
      has no observable regulatory effect and therefore, although an intramolecular
      contact between zippers B and C cannot be ruled out, such contact is not required
      for restraining the C-terminal activator domain. We furthermore find that
      deletions which abolish activator potential of the C-terminus render the host
      strain temperature sensitive. However, deletion of a double proline-glycine motif
      in the activator, whilst leaving HSF unable to respond to heat shock, does not
      cause temperature sensitivity. This result demonstrates that independent
      mechanisms control the transient and sustained activities of HSF.

PMID- 8262044
TI  - Specific interaction of IHF with RIBs, a class of bacterial repetitive DNA
      elements located at the 3' end of transcription units.
AB  - The prokaryotic REP (repetitive extragenic palindromes) or PU (palindromic units)
      sequences are often associated with other repetitive elements, forming
      arrangements which have been called 'BIMEs' (bacterial interspersed mosaic
      elements). It is estimated that the Escherichia coli chromosome carries
      approximately 300-500 BIMEs, whose biological role is at present unknown. We have
      identified a family of BIMEs consisting of two converging REP sequences flanking
      a 35 bp conserved segment which carries a static DNA bend and a binding site for
      IHF, the integration host factor of E.coli. We estimate that the E.coli genome
      harbors approximately 100 copies of this module, which we name 'RIB' (reiterative
      ihf BIME). We have analyzed by gel retardation and by footprinting the in vitro
      interaction of IHF with individual RIBs, and shown that the protein binds
      strongly and specifically to their center. We have also demonstrated binding of
      IHF to the chromosomal population of RIBs, using a new approach which combines
      two-dimensional bandshift and Southern blotting. RIB elements are at the end of
      transcription units, and thus define a new class of ihf sites. Possible
      implications for genome structure and DNA topology are discussed.

PMID- 8262045
TI  - The patterns of binding of RAR, RXR and TR homo- and heterodimers to direct
      repeats are dictated by the binding specificites of the DNA binding domains.
AB  - We show here that, in addition to generating an increase in DNA binding
      efficiency, heterodimerization of retinoid X receptor (RXR) with either retinoic
      acid receptor (RAR) or thyroid hormone receptor (TR) alters the binding site
      repertoires of RAR, RXR and TR homodimers. The binding site specificities of both
      homo- and heterodimers appear to be largely determined by their DNA binding
      domains (DBDs), and are dictated by (i) homocooperative DNA binding of the RXR
      DBD, (ii) heterocooperative DNA binding of RXR/RAR and RXR/TR DBDs, and (iii)
      steric hindrance. No homodimerization domain exists in the DBDs of TR and RAR.
      The dimerization function which is located in the ligand binding domain further
      stabilizes, but in general does not change, the repertoire dictated by the
      corresponding DBD(s). The binding repertoire can be further modified by the
      actual sequence of the binding site. We also provide evidence supporting the view
      that the cooperative binding of the RXR/RAR and RXR/TR DBDs to directly repeated
      elements is anisotropic, with interactions between the dimerization interfaces
      occurring only with RXR bound to the 5' located motif. This polarity, which
      appears to be maintained in the full-length receptor heterodimers, may constitute
      a novel parameter in promoter-specific transactivation.

PMID- 8262046
TI  - Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF
      kappa B: positive regulation by members of the rel/NF-kappa B family.
AB  - In order to characterize the regulation of the gene encoding the I kappa B
      alpha/MAD3 inhibitor of the transcription factor NF-kappa B, we have isolated a
      human genomic clone and sequenced the promoter of this gene. The MAD3 promoter
      exhibits a potential TATA element upstream of one of the two major transcription
      sites, and contains several potential NF-kappa B binding sequences, suggesting
      that the gene is positively regulated by members of this family. Transfection
      experiments demonstrate that the MAD3 promoter can be activated by various
      combinations of members of the rel/NF-kappa B family, as well as by phorbol
      esters and tumor necrosis factor. Specific deletion of one of the kappa B motifs,
      located 37 bp upstream of the TATA box, abolishes responses to PMA and TNF. This
      kappa B motif binds NF-kappa B (p50/relA), p50/c-rel and relA/c-rel heterodimers
      as well as KBF1 (p50 homodimer). These results help to explain the previously
      observed transient nature of the NF-kappa B response: following NF-kappa B
      activation, the expression of the inhibitor is increased, therefore the extent of
      nuclear translocation of the active complex is reduced, resulting in a decreased
      activation of its target genes.

PMID- 8262047
TI  - MAC1, a nuclear regulatory protein related to Cu-dependent transcription factors
      is involved in Cu/Fe utilization and stress resistance in yeast.
AB  - The related transcription factors ACE1 of Saccharomyces cerevisiae and AMT1 of
      Candida glabrata are involved in copper metabolism by activating the
      transcription of copper metallothionein genes. ACE1 and AMT1 are 'copper-fist'
      transcription factors which possess a conserved cysteine-rich copper binding
      domain required for DNA binding. Here we report the identification of a nuclear
      protein from S. cerevisiae, MAC1, whose N-terminal region is highly similar to
      the copper and DNA binding domains of ACE1 and AMT1. Loss-of-function mutants of
      MAC1 have a defect in the plasma membrane Cu(II) and Fe(III) reductase activity,
      are slow growing, respiratory deficient, and hypersensitive to heat and exposure
      to cadmium, zinc, lead and H2O2. Conversely, a dominant gain-of-function mutant
      of MAC1 shows an elevated reductase activity and is hypersensitive to copper. We
      have identified two target genes of MAC1 whose altered expression in mutants of
      MAC1 can account for some of the observed mutant phenotypes. First, MAC1 is
      involved in basal level transcription of FRE1, encoding a plasma membrane
      component associated with both Cu(II) and Fe(III) reduction. Second, MAC1 is
      involved in the H2O2-induced transcription of CTT1, encoding the cytosolic
      catalase. This suggests that MAC1 may encode a novel metal-fist transcription
      factor required for both basal and regulated transcription of genes involved in
      Cu/Fe utilization and the stress response.

PMID- 8262048
TI  - Conformational shifts propagate from the oligomerization domain of p53 to its
      tetrameric DNA binding domain and restore DNA binding to select p53 mutants.
AB  - p53 is a conformationally flexible sequence-specific DNA binding protein mutated
      in many human tumors. To understand why the mutant p53 proteins associated with
      human tumors fail to bind DNA, we mapped the DNA binding domain of wild-type p53
      and examined its regulation by changes in the protein conformation. Using site
      directed mutagenesis, residues 90-286 of mouse p53 were shown to form the
      sequence-specific DNA binding domain. Two highly conserved regions within this
      domain, regions IV and V, were implicated in contacting DNA. Wild-type p53 bound
      DNA as a tetramer, each subunit recognizing five nucleotides of the 20 nucleotide
      long DNA site. Conformational shifts of the oligomerization domain propagated to
      the tetrameric DNA binding domain, regulating DNA binding activity, but did not
      affect the subunit stoichiometry of wild-type p53 oligomers. Interestingly,
      conformational shifts could also be propagated within certain p53 mutants,
      rescuing DNA binding. One of these mutants was the mouse equivalent of human
      histidine 273, which is frequently associated with human tumors.

PMID- 8262049
TI  - Inhibition of hematopoietic development from embryonic stem cells by antisense
      vav RNA.
AB  - The vav proto-oncogene is universally and specifically expressed in hematopoietic
      cells. vav contains a unique array of motifs allowing the protein to function as
      a signal transducer and possibly as a transcription factor. Under certain in
      vitro culture conditions murine embryonic stem cells develop into colonies
      containing multiple hematopoietic lineages. In embryonic stem cell lines,
      constitutively expressing high levels of antisense vav transcripts through a
      stably integrated transgene, differentiation into hematopoietic cells is
      disrupted. This observation presents the first evidence that vav has a critical
      role in the development of hematopoietic cells from totipotent cells.

PMID- 8262050
TI  - Transcription activation by Myc and Max: flanking sequences target activation to
      a subset of CACGTG motifs in vivo.
AB  - The Myc oncoprotein has been implicated in control of cell growth, division and
      differentiation. Although Myc contains a bHLH-LZ motif, it fails to bind DNA
      alone but can do so by forming heterodimers with an unrelated bHLH-LZ protein,
      Max. Max homodimers and Myc-Max heterodimers share the ability to bind CACGTG or
      CATGTG elements. Current models, based on experimentally induced overexpression
      of Myc and Max in mammalian cells, propose that Max-Max homodimers repress while
      Myc-Max heterodimers activate transcription through CACGTG binding sites. The
      interpretation of the results using mammalian cells is complicated by the
      presence of numerous unrelated CACGTG binding transcription activators and the
      existence of two alternative Max dimerization partners, Mad and Mxi-1. Thus, the
      mechanism whereby overexpression of Max leads to transcriptional repression
      remains to be established. Using a yeast system we show that Max homodimers have
      the potential to activate transcription through CACGTG motifs. Activation by Max
      requires DNA binding and amino acids outside the bHLH-LZ domain but is reduced
      compared with activation by Myc-Max heterodimers. Moreover, transcriptional
      activation by Myc-Max heterodimers, but not Max-Max homodimers, is strongly
      inhibited in vivo by specific sequences flanking the core CACGTG binding motif,
      presumably reflecting reduced DNA binding affinity. These results suggest a
      mechanism for directing the Myc-Max complex to a specific subset of CACGTG
      containing target genes.

PMID- 8262051
TI  - The c-Myc protein induces cell cycle progression and apoptosis through
      dimerization with Max.
AB  - The c-Myc protein (Myc) is involved in cellular transformation and mitogenesis,
      but is also a potent inducer of programmed cell death, or apoptosis. Whether
      these apparently opposite functions are mediated through common or distinct
      molecular mechanisms remains unclear. Myc and its partner protein, Max, dimerize
      and bind DNA in vitro and in vivo through basic/helix-loop-helix/leucine zipper
      motifs (bHLH-LZ). By using complementary leucine zipper mutants (termed MycEG and
      MaxEG), which dimerize efficiently with each other but not with their wild-type
      partners, we demonstrate that both cell cycle progression and apoptosis in
      nontransformed rodent fibroblasts are induced by Myc-Max dimers. MycEG or MaxEG
      alone are inactive, but co-expression restores ability to prevent withdrawal from
      the cell cycle and to induce cell death upon removal of growth factors. Thus, Myc
      can control two alternative cell fates through dimerization with a single
      partner, Max.

PMID- 8262052
TI  - Functional interference between the Spi-1/PU.1 oncoprotein and steroid hormone or
      vitamin receptors.
AB  - The Spi-1/PU.1 protein is an Ets-related transcription factor, whose
      overexpression is a consequence of SFFV integration in Friend erythroleukemic
      cells. We present evidence that Spi-1/PU.1 can specifically repress the
      glucocorticoid-induced activation of promoters carrying a glucocorticoid response
      element (GRE). Conversely, the glucocorticoid receptor (GR) represses Spi-1/PU.1
      mediated transcriptional activation in the presence of hormone. Spi-1/PU.1 also
      antagonized activation by other nuclear receptors, such as the thyroid hormone or
      the retinoic acid receptors, in several cell lines, including K562
      erythroleukemic cells. These observations suggest that accumulation of the Spi
      1/PU.1 protein may interfere with the action of hormones in the erythrocyte
      differentiation pathway.

PMID- 8262053
TI  - Activation of ternary complex factor Elk-1 by MAP kinases.
AB  - Ternary complex factors (TCFs), one of which is Elk-1, have been implicated in
      mediation of c-fos induction. They have been shown to be phosphorylated by
      mitogen-activated protein kinases (MAPKs) in vitro. We demonstrate that
      recombinant Elk-1 is hyperphosphorylated in vivo upon joint overexpression of
      MAPKs and constitutively activated Raf-1 kinase, the latter serving as an
      indirect in vivo activator of MAPKs. This phosphorylation is accompanied by a
      conformational change and results in an elevated transactivation potential of Elk
      1. Mutation of mapped in vivo phosphorylation sites, which are potential targets
      for MAPKs, reduced Elk-1-mediated transcription. Thus, MAPKs are very probably
      controlling Elk-1 activity by direct phosphorylation in vivo. Furthermore, Elk-1
      was shown to stimulate transcription from both the c-fos serum response element
      and also from an Ets binding site. While binding of TCFs to the c-fos promoter is
      dependent on the serum response factor, TCFs can autonomously interact with Ets
      binding sites. This indicates that TCFs may participate in the transcriptional
      regulation of two different sets of genes.

PMID- 8262055
TI  - Definition and spatial location of mouse interleukin-2 residues that interact
      with its heterotrimeric receptor.
AB  - The high affinity receptor for interleukin-2 (IL-2) contains three subunits
      called IL-2R alpha, beta and gamma. A biological and receptor binding analysis
      based on 1393 different mutant mouse IL-2 (mIL-2) proteins was used to define the
      function of each of the 149 residues. By this genetic analysis, 44 residues were
      assigned important functions, 21 of which were structural. The remaining 23
      residues consisted of 19 residues, from three separate regions, that were
      important for IL-2R alpha interaction; three residues, from two separate regions,
      that were important for IL-2R beta interaction; and a single residue important
      for IL-2R gamma interaction. We built a model mIL-2 structure based on the
      homologous human IL-2 (hIL-2) crystal structure. The roles of the 21 residues
      presumed to be important for structure were consistent with the model. Despite
      discontinuity in the primary sequence, the residues specific for each IL-2R
      subunit interaction were clustered and located to three disparate regions of the
      tertiary mIL-2 structure. The relative spatial locations of these three surfaces
      are different from the two receptor binding sites known for the structurally
      related human growth hormone and the significance of this observation is
      discussed.

PMID- 8262054
TI  - The (YXXL/I)2 signalling motif found in the cytoplasmic segments of the bovine
      leukaemia virus envelope protein and Epstein-Barr virus latent membrane protein
      2A can elicit early and late lymphocyte activation events.
AB  - The cytoplasmic domains of the transducing subunits associated with B and T cell
      antigen receptors contain a common amino acid motif consisting of two precisely
      spaced Tyr-X-X-Leu/Ile sequences (where X corresponds to a variable residue).
      Expression of a single copy of this motif suffices to initiate B or T cell
      activation. The bovine leukaemia virus (BLV) is a B cell lymphotropic retrovirus
      which causes a non-neoplasic proliferation of B cells. The cytoplasmic domain of
      the BLV transmembrane envelope glycoprotein, gp30, possesses two overlapping
      copies of the Tyr-X-X-Leu/Ile-containing motif which could participate in the
      induction of B cell activation. Similarly, the N-terminal cytoplasmic domain of
      the latent membrane protein 2A (LMP2A) of the Epstein-Barr virus (EBV) contains a
      single copy of the Tyr-X-X-Leu/Ile-containing motif which could play a critical
      role in B cell transformation. To determine whether these two virus-encoded
      cytoplasmic domains are endowed with signalling functions, we constructed
      chimeric proteins by replacing the cytoplasmic tail of CD8-alpha with that of
      either BLV gp30 or EBV LMP2A. We show here that, once separately expressed in B
      or T cell lines, these chimeras are capable of triggering both calcium responses
      and cytokine production when cross-linked with an antibody to CD8-alpha.
      Furthermore, using site-directed mutagenesis, we demonstrated unequivocally that
      this signalling function may be accounted for by the Tyr-X-X-Leu/Ile motifs they
      contain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262056
TI  - Two distinct functional sites of human interleukin 4 are identified by variants
      impaired in either receptor binding or receptor activation.
AB  - Interleukin 4 (IL-4) exerts a decisive role in the coordination of protective
      immune responses against parasites, particularly helminths. A disregulation of IL
      4 function is possibly involved in the genesis of allergic disease states. The
      search for important amino acid residues in human IL-4 by mutational analysis of
      charged invariant amino acid positions identified two distinct functional sites
      in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of
      the glutamic acid at position 9 in helix A and arginine at position 88 in helix
      C. Exchanges at both positions led to IL-4 variants deficient in binding to the
      extracellular domain of the IL-4 receptor (IL-4R(ex)). In parallel, up to 1000
      fold increased concentrations of this type of variant were required to induce T
      cell proliferation and B-cell CD23 expression. Site 2 was marked by amino acid
      exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine
      respectively in the wild-type). IL-4 variants affected at site 2 exhibited
      partial agonist activity during T-cell proliferation; however, they still bound
      with high affinity to IL-4R(ex). [The generation of an IL-4 antagonist by
      replacing tyrosine 124 with aspartic acid has been described before by Kruse et
      al. (1992) (EMBO J., 11, 3237-3244)]. These findings indicate that IL-4 functions
      by binding IL-4R(ex) via site 1 which is constituted by residues on helices A and
      C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262057
TI  - A nuclear pathway for alpha 1-adrenergic receptor signaling in cardiac cells.
AB  - alpha 1-Adrenergic agonists and antagonists constitute an important class of
      therapeutic agents commonly used for the treatment of various cardiovascular
      diseases like hypertension, congestive heart failure and supraventricular
      tachycardia. At the heart level, activation of alpha 1-adrenergic receptors is
      associated with marked morphological and genetic changes. These include
      enhancement of contractility, myocardial growth (hypertrophy) and release of the
      heart major secretory product, atrial natriuretic factor (ANF). However, the
      signal transduction pathways which link extracellular activation of the receptors
      to cellular and genetic changes are not well understood. Using primary cardiocyte
      cultures from neonate rat hearts, an alpha 1-adrenergic regulatory sequence has
      been identified in the 5' flanking region of the ANF gene. This sequence, which
      is necessary and sufficient for transcriptional activation in response to the
      alpha 1-specific agonist phenylephrine, interacts with novel zinc-dependent
      proteins which are induced by alpha 1-adrenergic stimulation. Consistent with a
      conserved regulatory mechanism, the alpha 1 response element is highly conserved
      between rodent, bovine and human ANF genes, and is also present in the promoter
      region of other alpha 1-responsive cardiac genes. The identification of a nuclear
      pathway for alpha 1-receptor signaling will be useful for elucidating the
      intracellular effectors of alpha 1-adrenergic receptors.

PMID- 8262058
TI  - rho family GTPase activating proteins p190, bcr and rhoGAP show distinct
      specificities in vitro and in vivo.
AB  - rho family GTPases link extracellular signals to changes in the organization of
      cytoskeletal actin. Serum stimulation of quiescent Swiss 3T3 fibroblasts leads to
      rho-dependent actin stress fibre formation and focal adhesions, whilst several
      growth factors initiate signalling pathways leading to rac-dependent actin
      polymerization at the plasma membrane, and membrane ruffling. The product of the
      breakpoint cluster region gene bcr, rho GTPase accelerating protein (rhoGAP) and
      rasGAP-associated p190 share structurally related rho GAP domains, and possess
      GAP activity for rho family members in vitro. We have directly compared the
      activities of the isolated GAP domains of these three proteins in regulating
      different rho family GTPases, both by in vitro assays and by microinjection, to
      address their possible physiologic functions. We show that bcr accelerates the
      GTPase activity of rac, but not rho in vitro, and inhibits rac-mediated membrane
      ruffling, but not rho-mediated stress fibre formation, after microinjection into
      Swiss 3T3 fibroblasts. In vitro, rhoGAP has a striking preference for G25K as a
      substrate, whilst p190GAP has marked preferential activity for rho. Furthermore,
      p190 preferentially inhibits rho-mediated stress fibre formation in vivo. Our
      data suggest that p190, rhoGAP and bcr play distinct roles in signalling pathways
      mediated through different rho family GTPases.

PMID- 8262059
TI  - Mutation of Tyr697, a GRB2-binding site, and Tyr721, a PI 3-kinase binding site,
      abrogates signal transduction by the murine CSF-1 receptor expressed in Rat-2
      fibroblasts.
AB  - The receptor for the myeloid cell growth factor colony stimulating factor 1 (CSF
      1) is a protein tyrosine kinase that is closely related to the PDGF receptor.
      Ligand binding results in kinase activation and autophosphorylation. Three
      autophosphorylation sites, Tyr697, Tyr706 and Tyr721, have been mapped to the
      kinase insert domain. Deletion of the entire kinase insert domain completely
      abrogates signal transduction by the CSF-1 receptor expressed in Rat-2
      fibroblasts. To investigate the function of individual phosphorylation sites
      present in the CSF-1 receptor kinase insert domain, a number of phosphorylation
      site mutants were expressed in Rat-2 fibroblasts. Mutation of either Tyr697 or
      Tyr721 compromised signal transduction by the CSF-1 receptor. A mutant receptor,
      in which both Tyr697 and Tyr721 were replaced by phenylalanine, has lost all
      ability to induce changes in morphology or to increase cell growth rate in
      response to CSF-1. Tyr721 has been identified recently as the binding site for PI
      3-kinase. Here we report that GRB2 associates with the CSF-1 receptor upon ligand
      binding. The phosphorylation on tyrosine of SHC and several other GRB2-associated
      proteins increased upon stimulation with CSF-1. Tyr697 was identified as a
      binding site for GRB2. We suggest that PI 3-kinase, GRB2 and some of the GRB2
      associated proteins could play an important role in signal transduction by the
      CSF-1 receptor.

PMID- 8262060
TI  - Interaction of intronic boundaries is required for the second splicing step
      efficiency of a group II intron.
AB  - Group II and nuclear pre-mRNAs introns share a common splicing pathway involving
      a lariat intermediate, as well as some primary sequence similarities at the
      splice junctions. In this work, we analyze the role of the conserved nucleotides
      at the first and penultimate positions (G1 and A886) of a group II self-splicing
      intron. We show that the G1 nucleotide is essential for the efficiency of both
      the first and the second splicing steps, while substitutions at the penultimate
      nucleotide affect mostly the efficiency of the second step. A reciprocal
      suppression of the second splicing step defect can be observed in some double
      mutants. This result is best explained by a non-Watson-Crick interaction between
      the first and the penultimate nucleotides of the intron, which occurs after
      lariat formation. The finding that an interaction between intron boundaries is
      required for the second splicing step in both group II and nuclear pre-mRNA
      introns strengthens the idea that both systems employ similar mechanisms, albeit
      with differences in the details of the nucleotide interactions.

PMID- 8262061
TI  - Mutations in the conserved loop of human U5 snRNA generate use of novel cryptic
      5' splice sites in vivo.
AB  - We have analyzed base pairing interactions between the U5 snRNA and 5' exon
      sequences during pre-mRNA splicing in a mammalian in vivo system. We constructed
      synthetic U5 genes with mutations that alter four bases (C3, U4, U5 and U6)
      within the invariant 9 nt U5 sequence GCCUUUUAC; transient transfection of HeLa
      cells with these U5 sequences cloned into a U1 expression vector yielded high
      levels of the mutant snRNAs. To test their function, we cotransfected a rabbit
      beta-globin gene containing one of two mutations (G1-->A or T2-->A) in the
      essential GT dinucleotide at the 5' end of the second intron. Certain U5 loop
      mutants activated novel 5' splice sites only in mutant rabbit beta-globin
      transcripts. One novel site surprisingly resides in the first exon; its use is
      invariably coupled to utilization of a particular cryptic 5' splice site in the
      second exon. All of the newly activated cryptic 5' splice sites exhibit
      complementarity with the mutant U5 loop in the exon 1-5 nt upstream of the
      cryptic site, extending previous results in yeast. However, the register of the
      potential pairing is not identical at the various novel cryptic 5' splice sites,
      indicating that the interaction between the U5 loop and the 5' exon may be more
      flexible than previously believed.

PMID- 8262062
TI  - A complex secondary structure in U1A pre-mRNA that binds two molecules of U1A
      protein is required for regulation of polyadenylation.
AB  - The human U1A protein-U1A pre-mRNA complex and the relationship between its
      structure and function in inhibition of polyadenylation in vitro were
      investigated. Two molecules of U1A protein were shown to bind to a conserved
      region in the 3' untranslated region of U1A pre-mRNA. The secondary structure of
      this region was determined by a combination of theoretical prediction,
      phylogenetic sequence alignment, enzymatic structure probing and molecular
      genetics. The U1A binding sites form (part of) a complex secondary structure
      which is significantly different from the binding site of U1A protein on U1
      snRNA. Studies with mutant pre-mRNAs showed that the integrity of much of this
      structure is required for both high affinity binding to U1A protein and specific
      inhibition of polyadenylation in vitro. In particular, binding of a single
      molecule of U1A protein to U1A pre-mRNA is not sufficient to produce efficient
      inhibition of polyadenylation.

PMID- 8262063
TI  - Focal localization of the NHE-1 isoform of the Na+/H+ antiport: assessment of
      effects on intracellular pH.
AB  - Na+/H+ exchange (antiport) is a major pathway for the regulation of intracellular
      pH. Antiport activity is stimulated when suspended cells adhere to the
      substratum. In this report, immunofluorescence was used to study the subcellular
      localization of the ubiquitous NHE-1 isoform of the antiport. NHE-1 was not
      distributed homogeneously on the surface of the cells. Instead, antiports were
      found to accumulate along the border of lamellipodia and near the edge of finer
      processes. Dual immunofluorescence experiments demonstrated that vinculin, talin
      and F-actin are concentrated at sites of NHE-1 accumulation. A mutated construct
      of NHE-1 lacking residues 566-635 of the cytosolic domain also accumulated near
      marginal lamellae. In contrast, the focal distribution observed in adherent cells
      was not detectable in cells grown in suspension. Fluorescence ratio imaging was
      used to define the functional consequences of focal accumulation of NHE-1. In the
      steady state, the pH was virtually identical throughout the cytosol. Moreover, no
      pH gradients were found to develop when cells recovered from an acid load by
      activation of Na+/H+ exchange. This is probably because of the presence of high
      concentrations of mobile buffers in the cytosol. The focal accumulation of
      antiporters near the cell margins may be involved in stimulation by adherence
      and/or generation of local osmotic gradients.

PMID- 8262064
TI  - Targeted disruption of the M(r) 46,000 mannose 6-phosphate receptor gene in mice
      results in misrouting of lysosomal proteins.
AB  - Lysosomal enzymes containing mannose 6-phosphate recognition markers are sorted
      to lysosomes by mannose 6-phosphate receptors (MPRs). The physiological
      importance of this targeting mechanism is illustrated by I-cell disease, a fatal
      lysosomal storage disorder caused by the absence of mannose 6-phosphate residues
      in lysosomal enzymes. Most mammalian cells express two MPRs. Although the binding
      specificities, subcellular distribution and expression pattern of the two
      receptors can be differentiated, their coexpression is not understood. The larger
      of the two receptors with an M(r) of approximately 300,000 (MPR300), which also
      binds IGFII, appears to have a dominant role in lysosomal enzyme targeting, while
      the function of the smaller receptor with an M(r) of 46,000 (MPR46) is less
      clear. To investigate the in vivo function of the MPR46, we generated MPR46
      deficient mice using gene targeting in embryonic stem cells. Reduced
      intracellular retention of newly synthesized lysosomal proteins in cells from
      MPR46 -/- mice demonstrated an essential sorting function of MPR46. The phenotype
      of MPR46 -/- mice was normal, indicating mechanisms that compensate the MPR46
      deficiency in vivo.

PMID- 8262065
TI  - Targeted disruption of the mouse cation-dependent mannose 6-phosphate receptor
      results in partial missorting of multiple lysosomal enzymes.
AB  - In mammalian cells two mannose 6-phosphate receptors (MPRs) are involved in
      lysosomal enzyme transport. To understand the precise function of the cation
      dependent mannose 6-phosphate receptor (CD-MPR), one allele of the corresponding
      gene has been disrupted in mouse embryonic stem cells and homozygous mice lacking
      this receptor have been generated. The homozygous mice appear normal, suggesting
      that other targeting mechanisms can partially compensate for the loss of the CD
      MPR in vivo. However, homozygous receptor-deficient cells and animals clearly
      exhibit defects in targeting of multiple lysosomal enzymes when compared with
      wild-types. Increased levels of phosphorylated lysosomal enzymes were present in
      body fluids of homozygous animals. In thymocytes from homozygous mice or in
      primary cultures of fibroblasts from homozygous embryos, there is a marked
      increase in the amount of phosphorylated lysosomal enzymes that are secreted into
      the extracellular medium. The cultured fibroblasts have decreased intracellular
      levels of multiple lysosomal enzymes and accumulate macromolecules within their
      endosomal/lysosomal system. Taken together, these results clearly indicate that
      the CD-MPR is required for efficient intracellular targeting of multiple
      lysosomal enzymes.

PMID- 8262066
TI  - The beta 1 and beta 2 subunits of the AP complexes are the clathrin coat assembly
      components.
AB  - The beta 1 and beta 2 subunits are the closely-related large chains of the trans
      Golgi network AP-1 and the plasma membrane AP-2 clathrin-associated protein
      complexes, respectively. Recombinant beta 1 and beta 2 subunits have been
      generated in Escherichia coli. It was found that, in the absence of all the other
      AP subunits, beta 1 and beta 2 interact with clathrin and drive the efficient
      assembly of clathrin coats. In addition, beta 2 subunits and AP complexes compete
      for the same clathrin binding site. The appearance of the clathrin/beta coats is
      the same as the barrel-shaped structures formed with native AP complexes. It is
      proposed that the principal function of the beta subunits is to initiate coat
      formation, while the remaining subunits of the AP complexes have other roles in
      coated pit and coated vesicle function.

PMID- 8262067
TI  - The Schizosaccharomyces pombe cwg2+ gene codes for the beta subunit of a
      geranylgeranyltransferase type I required for beta-glucan synthesis.
AB  - The product of the Schizosaccharomyces pombe cwg2+ gene is involved in the
      biosynthesis of beta-D-glucan. When grown at the non-permissive temperature, cwg2
      1 mutant cells lyse in the absence of an osmotic stabilizer and display a reduced
      (1-3) beta-D-glucan content and (1-3) beta-D-glucan synthase activity. The cwg2+
      gene was cloned by the rescue of the cwg2-1 mutant phenotype using an S. pombe
      genomic library and subsequently verified by integration of the appropriate
      insert into the S. pombe genome. Determination of the nucleotide sequence of this
      gene revealed a putative open reading frame of 1065 bp encoding a polypeptide of
      355 amino acids with a calculated M(r) of 40,019. The cwg2+ DNA hybridizes to a
      main transcript, the 5' end of which maps to a position 469 bp upstream of the
      predicted start of translation. The sequence between the transcription and the
      translation start sites is unusually long and has several short open reading
      frames which suggest a translational control of the gene expression. Comparative
      analysis of the predicted amino acid sequence shows that it possesses significant
      similarity to three Saccharomyces cerevisiae proteins, encoded by the DPR1/RAM1,
      CDC43/CAL1 and ORF2/BET2 genes respectively, which are beta subunits of different
      prenyltransferases. When grown at 37 degrees C, cwg2-1 mutant extracts were
      specifically deficient in geranylgeranyltransferase type I activity, as measured
      in vitro. Multiple copies of the CDC43 gene can partially suppress the growth and
      (1-3) beta-D-glucan synthase defect of the cwg2-1 mutant at the restrictive
      temperature. In a similar manner, the cwg2+ gene can partially suppress the cdc43
      2 growth defect. These results indicate that cwg2+ is the structural gene for the
      beta subunit of geranylgeranyltransferase type I in S. pombe and that this enzyme
      is required for (1-3) beta-D-glucan synthase activity. The functional homology of
      Cwg2 with Cdc43, which has been implicated in the control of cell polarity,
      suggests a link between two morphogenetic events such as establishment of cell
      polarity and cell wall biosynthesis.

PMID- 8262068
TI  - Characterization of NGG1, a novel yeast gene required for glucose repression of
      GAL4p-regulated transcription.
AB  - The GAL1-10 genes of Saccharomyces cerevisiae are regulated by the interaction of
      cis- and trans-acting factors which facilitate activated transcription in
      galactose but not in glucose medium. By selecting mutations that allow expression
      of a defective gal1-10-his3 hybrid promoter, we have identified a novel gene,
      NGG1, which is required for glucose repression of the GAL10-related his3-G25
      promoter. ngg1 was identified as a recessive null mutation that in the presence
      of a gal80 background resulted in a 300-fold relief of glucose repression for the
      his3-G25 promoter. This compared with a 20-fold and negligible relief of
      repression in gal80 and ngg1 strains, respectively. Deletion analysis of the his3
      G25 promoter showed a correlation between the number of GAL4p binding sites and
      the relative level of NGG1p activity. Relief of glucose repression by NGG1 was
      dependent on the presence of GAL4, but was independent of the GAL4 promoter. In
      addition, NGG1p activity was seen for a promoter construct containing independent
      GAL4p binding sites. These results suggest that NGG1p acts to inhibit GAL4p
      function in glucose medium. We have cloned NGG1 by complementation and found that
      it contains an open reading frame of 2106 bp which could encode a protein with a
      molecular weight of 79,230.

PMID- 8262069
TI  - Genetic analysis of Cln/Cdc28 regulation of cell morphogenesis in budding yeast.
AB  - The CLN1, CLN2 and CLN3 gene family of G1-acting cyclin homologs of Saccharomyces
      cerevisiae is functionally redundant: any one of the three Cln proteins is
      sufficient for activation of Cdc28p protein kinase activity for cell cycle START.
      The START event leads to multiple processes (including DNA replication and bud
      emergence); how Cln/Cdc28 activity activates these processes remains unclear.
      CLN3 is substantially different in structure and regulation from CLN1 and CLN2,
      so its functional redundancy with CLN1 and CLN2 is also poorly understood. We
      have isolated mutations that alter this redundancy, making CLN3 insufficient for
      cell viability in the absence of CLN1 and CLN2 expression. Mutations causing
      phenotypes specific for the cell division cycle were analyzed in detail.
      Mutations in one gene result in complete failure of bud formation, leading to
      depolarized cell growth. This gene was identified as BUD2, previously described
      as a non-essential gene required for proper bud site selection but not required
      for budding and viability. Bud2p is probably the GTPase-activating protein for
      Rsr1p/Bud1p [Park, H., Chant, I. and Herskowitz, I. (1993) Nature, 365, 269-274];
      we find that Rsr1p is required for the bud2 lethal phenotype. Mutations in two
      other genes (ERC10 and ERC19) result in a different morphogenetic defect: failure
      of cytokinesis resulting in the formation of long multinucleate tubes. These
      results suggest direct regulation of diverse aspects of bud morphogenesis by
      Cln/Cdc28p activity.

PMID- 8262070
TI  - Yeast G1 cyclins CLN1 and CLN2 and a GAP-like protein have a role in bud
      formation.
AB  - Cyclin-dependent protein kinases have a central role in cell cycle regulation. In
      Saccharomyces cerevisiae, Cdc28 kinase and the G1 cyclins Cln1, 2 and 3 are
      required for DNA replication, duplication of the spindle pole body and bud
      emergence. These three independent processes occur simultaneously in late G1 when
      the cells reach a critical size, an event known as Start. At least one of the
      three Clns is necessary for Start. Cln3 is believed to activate Cln1 and Cln2,
      which can then stimulate their own accumulation by means of a positive feedback
      loop. They (or Cln3) also activate another pair of cyclins, Clb5 and 6, involved
      in initiating S phase. Little is known about the role of Clns in spindle pole
      body duplication and budding. We report here the isolation of a gene
      (CLA2/BUD2/ERC25) that codes for a homologue of mammalian Ras-associated GTPase
      activating proteins (GAPs) and is necessary for budding only in cln1 cln2 cells.
      This suggests that Cln1 and Cln2 may have a direct role in bud formation.

PMID- 8262071
TI  - Critical intracellular Ca2+ concentration for all-or-none Ca2+ spiking in single
      smooth muscle cells.
AB  - Neurotransmitters induce contractions of smooth muscle cells initially by
      mobilizing Ca2+ from intracellular Ca2+ stores through inositol 1,4,5
      trisphosphate (InsP3) receptors. Here we studied roles of the molecules involved
      in Ca2+ mobilization in single smooth muscle cells. A slow rise in cytoplasmic
      Ca2+ ([Ca2+]i) in agonist-stimulated smooth muscle cells was followed by a wave
      of rapid regenerative Ca2+ release as the local [Ca2+]i reached a critical
      concentration of approximately 160 nM. Neither feedback regulation of
      phospholipase C nor caffeine-sensitive Ca(2+)-induced Ca2+ release was found to
      be required in the regenerative Ca2+ release. These results indicate that Ca(2+)
      dependent feedback control of InsP3-induced Ca2+ release plays a dominant role in
      the generation of the regenerative Ca2+ release. The resulting Ca2+ release in a
      whole cell was an all-or-none event, i.e. constant peak [Ca2+]i was attained with
      agonist concentrations above the threshold value. This finding suggests a
      possible digital mode involved in the neural control of smooth muscle
      contraction.

PMID- 8262072
TI  - Mutations in the segment polarity genes wingless and porcupine impair secretion
      of the wingless protein.
AB  - We have characterized the molecular nature of mutations in wingless (wg), a
      segment polarity gene acting during various stages of Drosophila development.
      Embryo-lethal alleles have undergone mutations in the protein-encoding domain of
      the gene, including deletions and point mutations of conserved residues. In a
      temperature sensitive mutation, a conserved cysteine residue is replaced by a
      serine. In embryo-viable alleles, the wg transcriptional unit is not affected.
      Immunostaining of mutant embryos shows that the embryo-lethal alleles produce
      either no wg antigen or a form of the protein that is retained within cells.
      Interestingly, embryos mutant for the segment polarity gene porcupine show a
      similar retention of the wg antigen. We have also transfected wild type wg
      alleles into Drosophila tissue culture cells, which then display wg protein on
      the cell surface and in the extracellular matrix. In similar experiments with
      mutant alleles, the proteins are retained in intracellular compartments and
      appear not to be secreted. These data provide further evidence that wg acts as a
      secreted factor and suggest that porcupine provides an accessory function for wg
      protein secretion or transport.

PMID- 8262073
TI  - Cloning and expression of Drosophila TAFII60 and human TAFII70 reveal conserved
      interactions with other subunits of TFIID.
AB  - Regulation of transcription initiation by RNA polymerase II requires TFIID, a
      multisubunit complex composed of the TATA binding protein (TBP) and at least
      seven tightly associated factors (TAFs). Some TAFs act as direct targets or
      coactivators for promoter-specific activators while others serve as interfaces
      for TAF-TAF interactions. Here, we report the molecular cloning, expression and
      characterization of Drosophila dTAFII60 and its human homolog, hTAFII70.
      Recombinant TAFII60/70 binds weakly to TBP and tightly to the largest subunit of
      TFIID, TAFII250. In the presence of TAFII60/70, TBP and TAFII250, a stable
      ternary complex is formed. Both the human and Drosophila proteins directly
      interact with another TFIID subunit, dTAFII40. Our findings reveal that
      Drosophila TAFII60 and human TAFII70 share a high degree of structural similarity
      and that their interactions with other subunits of TFIID are conserved.

PMID- 8262074
TI  - Surgical revascularization in the treatment of ventricular tachycardia and
      fibrillation exposed by exercise-induced ischaemia.
AB  - The role of myocardial revascularization in the treatment of malignant
      ventricular arrhythmias is not well defined. Our hypothesis was that in patients
      with ventricular tachycardia or fibrillation exposed by exercise-induced
      ischaemia, the acute transient ischaemia plays a principal causal role, and that
      in these patients surgical myocardial revascularization alone might be an
      effective treatment. Among 1100 consecutive patients undergoing isolated coronary
      artery bypass surgery (CABG) 30 patients (2.7%) characterized by ventricular
      tachycardia or fibrillation at the symptom-limited exercise tests prior to
      revascularization were studied prospectively. All patients had exercise-induced
      angina pectoris or ischaemic ST-segment depression preceding at least one of the
      arrhythmic events. In addition, eight of these 30 patients had experienced
      syncope during out-of-hospital exertional activities. After surgical
      revascularization, the 28 patients surviving to hospital discharge were followed
      for 1.6 to 86 months (mean 29 +/- 29 months) as outpatients and underwent between
      one to eight exercise tests (mean 2.6 +/- 1.9). One of these patients died
      suddenly of unknown causes at 14 months, another from cancer at 53 months. Twenty
      six patients experienced a total of 34 episodes of ventricular tachycardia before
      revascularization. Two of these patients, both having residual ischaemia, had
      arrhythmia recurrences during follow-up; odds ratio (OR) 84.5, 95% confidence
      interval (CI) 18.7-381.9; P = < 0.010. Exercise-induced ventricular fibrillation
      occurred in eight patients pre-operatively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262075
TI  - Interrelation of cardiac and vascular structure in young men with borderline
      hypertension.
AB  - It is not established whether left ventricular hypertrophy and structural
      vascular changes are primary phenomena or secondary consequences of raised blood
      pressure. In this study we investigated 54 borderline hypertensive men (BH) (SBP
      140-160 mmHg and/or DBP 84-95 mmHg) and 20 normotensive men (NC) (SBP 110-130
      mmHg and DBP 60-80 mmHg), recruited from an unbiased population sample (age 20 +/
      2 years). Blood pressure (BP) levels were confirmed by i.a. BP recordings. Left
      ventricular mass (LVM) was determined with M-mode echocardiography and minimal
      vascular resistance (Rmin) was calculated from the blood flow in the calf and
      forearm after maximal ischaemic work. Central haemodynamics were assessed by
      intra-arterial blood pressure recordings and cardiac output determinations by the
      dye dilution technique. In the BH group, LVM and Rmin were strongly correlated to
      body size, especially weight and body surface area. However, LVM and Rmin were
      only weakly correlated to blood pressure. In the normokinetic BH subgroup (NBH)
      (n = 38) minimal forearm vascular resistance was significantly higher than in the
      hyperkinetic BH individuals (HBH) (n = 16), indicating the presence of structural
      vascular changes in the former. Furthermore, in the NBH group there was a
      significant correlation between LVM and Rmin both in the calf (r = 0.490 P =
      0.002) and in the forearm (r = 0.520 P = 0.001). This association remained after
      correction for body size. No such correlation was seen in the HBH subgroup or in
      the NC group. The present study does give long-reaching conclusions as regards
      the aetiological factors underlying the cardiovascular remodelling. However, our
      data show that (1) cardiovascular changes appear early in the course of blood
      pressure elevation, (2) the cardiac and vascular changes develop in parallel, and
      (3) structural remodelling is not solely explained by the degree of blood
      pressure elevation since blood pressure was similar in the two BH subgroups.
      Thus, other factors than blood pressure appear to be important determinants of
      structural adaptation in mildly hypertensive states.

PMID- 8262076
TI  - Subjective symptoms and well-being differ in women and men after myocardial
      infarction.
AB  - The frequency of subjective cardiac and psychological complaints among men and
      women a year after a confirmed diagnosis of myocardial infarction (MI) were
      compared. Among 660 survivors, 595 patients completed mailed questionnaires at
      home one year after the MI. There were 421 men, mean age 67.1 +/- 10.7 years, and
      174 women, mean age 72.1 +/- 10.6 years. Controlling for the significantly higher
      mean age among the women, the latter more often had a previous history of angina
      pectoris, 54.6% (P < or = 0.05) versus 42.9%, and heart failure, 24.7% versus
      13.5% (P < or = 0.01). Despite these facts, the women were significantly less
      often referred to CCU, 82.2% versus 91.7% (P < or = 0.05). One year after the MI,
      controlling for differences in age and co-morbidity, women reported significantly
      higher frequencies of psychological and psychosomatic complaints, including sleep
      disturbances. These differences may have clinical implications for diagnosis and
      treatment of women with coronary heart disease.

PMID- 8262077
TI  - Effect of atrial fibrillation on pulmonary venous flow patterns: transoesophageal
      pulsed Doppler echocardiographic study.
AB  - The effect of atrial fibrillation on pulmonary venous flow patterns is still not
      well known. Twenty-four patients in atrial fibrillation and 21 patients in sinus
      rhythm were studied by transoesophageal echocardiography. In ninety-five percent
      (20/21) of sinus rhythm patients, the early systolic wave due to atrial
      relaxation or reverse wave due to atrial contraction could be distinguished on
      pulsed Doppler tracings by transoesophageal echocardiography. However, there was
      no early systolic wave and/or reverse at the end of diastole in any atrial
      fibrillation patients. In atrial fibrillation patients without mitral
      regurgitation (n = 14), the onset of systolic flow was delayed (165 +/- 38 vs 50
      +/- 46 ms, P < 0.05), and systolic peak velocities, time-velocity integrals and
      systolic fractions were reduced (31 +/- 13 vs 54 +/- 17 cm.s-1, P < 0.05; 5 +/- 2
      vs 13 +/- 6 cm, P < 0.05 and 36 +/- 8 vs 61 +/- 15%, P < 0.05, respectively) as
      compared to those in sinus rhythm. Significant mitral regurgitation (n = 10)
      reduced systolic velocity parameters considerably in atrial fibrillation patients
      but the diastolic flow parameters were not significantly different between sinus
      rhythm and atrial fibrillation patients. Stepwise multiple regression analysis
      identified atrial fibrillation as an important independent predictor for changes
      in systolic flow parameters. The R-R interval is also an important factor for
      diastolic flow parameters. Thus, the present study demonstrates that atrial
      fibrillation significantly modifies pulmonary venous flow pattern and is an
      important factor for systolic flow parameters. Significant mitral regurgitation
      can further modify systolic flow pattern in atrial fibrillation patients.

PMID- 8262078
TI  - Dipyridamole echocardiography evaluation of acute inferior myocardial infarction
      with concomitant anterior ST segment depression.
AB  - The significance of anterior ST segment depression in inferior acute myocardial
      infarction (AMI) remains controversial. The aim of this study was to relate
      precordial ST segment depression to the topography of residual myocardial
      ischaemia, with myocardial mapping of the asynergic area and coronary anatomy.
      Twenty-five patients with first inferior AMI (15 patients with anterior ST
      segment depression: group A and 10 patients without anterior ST segment shift:
      group B), all underwent: (1) electrocardiographic evaluation on admission to the
      Coronary Care Unit and at 24 h intervals thereafter; (2) 2D-echocardiographic
      study within 3 h of CCU admission; (3) dipyridamole echocardiographic test (DET)
      (doses of dipyridamole up to 0.84 mg.kg-1 i.v. over 10 min) 4 days after AMI; (4)
      coronary arteriography within 14 days from AMI. To assess regional left
      ventricular wall motion, a 16 segment model was used and a wall motion score
      index (WMSI) was derived. The results of DET were correlated to the anatomy of
      the infarct-related vessel. Compared to group B, group A patients showed a
      significantly greater maximal ST segment elevation in inferior limb leads (lead
      III: 3.9 +/- 1.9 mm vs 2.2 +/- 1.1 mm, P < 0.05; aVF: 3.5 +/- 1.3 mm vs 1.7 +/-
      0.8 mm, P < 0.001). Group A patients showed greater WMSI (1.35 +/- 0.22 vs 1.17
      +/- 0.12, P < 0.05), with more frequent postero-lateral wall involvement (72% vs
      20%, P < 0.05). No patient of either group showed asynergy of the anterior,
      anterolateral or anteroseptal segments. No differences in the distribution of
      coronary artery disease were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262079
TI  - Evidence of functional alterations in sympathetic activity after myocardial
      infarction.
AB  - To assess whether the presence of areas of efferent sympathetic denervation might
      contribute to alterations in sympathetic and vagal neural regulatory activities
      observed after myocardial infarction, we attempted to correlate the changes in
      the spectral components of RR variability with the I-123 MIBG and Thallium-201
      uptake defects. Ten patients with first and uncomplicated myocardial infarction
      were studied. Thallium-201 and I-123 MIBG scintigraphy as well as spectral
      analysis of heart rate variability were performed 7 days, 4, 12 and 30 months
      after the acute event. Regional abnormalities in I-123 MIBG uptake were more
      extensive than the perfusion defects indicated by Thallium-201 images and
      remained constant throughout the entire period of observation. In the early post
      infarction period, spectral analysis of RR variability was characterized by a
      predominant LF (74 +/- 6 nu) and a smaller HF (16 +/- 3 nu) component indicating
      a sympathetic predominance. Thereafter, we observed a progressive reduction in LF
      and a gradual increase in HF which were consistent with a normalization of
      sympatho-vagal balance. These data indicate that after a myocardial infarction,
      the presence and persistence of areas of sympathetic functional denervation do
      not seem to play a major role in determining the changes in sympathetic and vagal
      neural regulatory activities directed to the heart.

PMID- 8262080
TI  - Transmitral flow velocities and times during stress transthoracic
      echocardiography in patients with myocardial ischaemia.
AB  - Twenty-nine men with chronic stable angina pectoris were investigated using
      stress electrocardiography (ECG) and stress transthoracic echocardiography by
      means of transoesophageal stimulation of the left atrium. At rest and after each
      stimulated frequency, ECG and 2-dimensional echocardiography combined with
      Doppler were performed simultaneously. Fourteen patients without ischaemia at
      stress ECG and two patients who were subjected only to two different frequencies
      of stimulation were excluded from our study. Thirteen patients with ischaemic
      electrocardiographic response at stress, who were subjected to at least three
      stimulated frequencies, were evaluated. Their deceleration time of early
      transmitral filling was prolonged from 171 +/- 15.4 ms to 178.1 +/- 14.4 ms (P =
      ns) after the first stimulated frequency, to 172.8 +/- 15.1 ms after the second
      stimulated frequency (P = ns) and was shortened to 143.6 +/- 7.9 ms (P < 0.05)
      after the fastest stimulated frequency. The ratio of peak transmitral flow
      velocity in early diastole (E) to that during atrial contraction (A) decreased
      from 0.93 +/- 0.07 at rest to 0.85 +/- 0.07 (P < 0.05) after the first stimulated
      frequency, to 0.87 +/- 0.07 (P = ns) after the second stimulated frequency and
      increased to 1.13 +/- 0.08 (P < 0.05) after the fastest stimulated frequency. In
      patients with angina pectoris and myocardial ischaemia, the changes in the E/A
      ratio and deceleration time during stress are not linear and their direction
      depends on the moment of their evaluation. Their use for the quantitative
      evaluation of the diastolic function of the left ventricle is problematic.

PMID- 8262081
TI  - Down-regulation of beta-adrenergic receptors on mononuclear leukocytes induced by
      dobutamine treatment in patients with congestive heart failure.
AB  - (+/-)-Dobutamine is a positive inotropic drug usually used to improve ventricular
      function in patients with congestive heart failure (CHF). However, it has been
      found that haemodynamic responses to dobutamine become blunted during continuous
      treatment. In this study we determined the time-dependent changes of beta
      adrenergic receptors in CHF patients treated with dobutamine. Seven CHF patients
      received a continuous intravenous infusion of dobutamine (5 micrograms.kg-1 x min
      1) for 96 h. Blood samples were obtained before and every 24 h after starting the
      therapy. The density of beta-adrenergic receptors on mononuclear leukocytes and
      the plasma concentrations of norepinephrine and epinephrine were determined.
      During dobutamine treatment the receptor density (fmol.mg-1, mean +/- SEM)
      gradually decreased from 42.8 +/- 4.4 (baseline) to 31.4 +/- 3.3 (P < 0.05), 25.2
      +/- 4.0 (P < 0.01), 18.8 +/- 5.5 (P < 0.01) and 13.4 +/- 3.4 (P < 0.01) at 24,
      48, 72 and 96 h, respectively. However, the plasma concentrations of
      norepinephrine and epinephrine were not significantly changed during the 96 h
      period of treatment. Thus, the beta-adrenergic receptors down-regulated as early
      as 24 h after the dobutamine treatment was begun in CHF patients. This receptor
      down-regulation was not associated with changes of plasma catecholamine
      concentrations, but was related rather to the development of drug tolerance to
      dobutamine.

PMID- 8262082
TI  - The impact of balloon angioplasty of coronary artery and/or vein bypass graft
      lesion(s) upon the survival of patients > or = 5 years after their last bypass
      surgery.
AB  - Data analyses of angioplasty patients, whose operative and angioplasty (PTCA)
      interval was > or = 5 years, were performed to determine if the site of PTCA
      (coronary artery (CA) and/or vein bypass graft (VG)) influenced longevity. PTCA
      was successful in 677/768 lesions (88%) (377/432 CA (87%), and 294/327 VGs (90%))
      and resulted in clinical improvement in 280/322 patients (87%). Patients were
      stratified into those who underwent PTCA of a lesion(s) in a coronary artery
      only, a vein graft only, or in both a coronary artery and a vein graft. Survival,
      at 60 months, was adversely affected (P < 0.05) for VG (59%) in comparison to CA
      (86%) or CA + VG (86%) cohorts, which was reaffirmed by a Cox proportional hazard
      model. PTCA was effective in opening lesions in coronary arteries or vein grafts
      in patients whose last bypass surgery had occurred over 5 years previously;
      however, PTCA patients who only had a vein graft had a significantly diminished 5
      year survival in comparison to the cohorts, who had a coronary artery lesion
      dilated, with or without an accompanying vein graft PTCA. Therefore, PTCA of
      isolated vein graft lesions may not be the best long-term therapeutic option for
      these patients; however, it may best serve patients, acutely and long-term, who
      have an amenable significant arterial lesion, whether or not an accompanying vein
      graft lesion is dilated.

PMID- 8262083
TI  - Graduated compression stockings in the prevention of deep vein thrombosis in
      patients with acute myocardial infarction.
AB  - Venous volume (venous capacity) of the calf is low in patients with acute
      myocardial infarction, who also have a high risk of deep vein thrombosis (DVT).
      The effect of graduated compression stockings on the venous volume and on the
      incidence of DVT was therefore studied in 80 patients aged 70 years and above
      with acute myocardial infarction. Graduated compression stockings were randomly
      fitted to one leg, the other serving as a control, after which the venous volume
      was measured by strain gauge plethysmography. The incidence of DVT was measured
      by the 125I fibrinogen uptake test. Venous volume was significantly higher in
      legs treated with graduated compression stockings compared to control legs. DVT
      developed in eight control legs but not in any leg treated with graduated
      compression stockings (P = 0.003). DVT was also significantly more frequent in
      women compared to men and the majority of DVT developed in legs with very low
      venous volume values.

PMID- 8262084
TI  - Atenolol versus the fixed combination of atenolol and nifedipine in stable angina
      pectoris.
AB  - One hundred and fourteen patients (94 male) with chronic stable angina who had a
      positive exercise test after 4 weeks on atenolol alone were randomized to receive
      either atenolol alone or the fixed combination of atenolol and nifedipine slow
      release formulation for 4 weeks in a double-blind cross-over manner. Exercise
      stress testing (Bruce protocol) at the end of each treatment period demonstrated
      that the time to the onset of pain and occurrence of 1 mm ST segment depression
      improved significantly (P < 0.05 and P < 0.001 respectively) whilst on the fixed
      combination compared to atenolol alone. In order to achieve sufficient
      sensitivity in the analysis of the exercise times, novel statistical methods
      based on survival analysis were used. Maximum ST segment depression was 0.13 mm
      less (P < 0.04) while on the fixed combination. The incidence of withdrawals and
      adverse effects was similar on both treatments.

PMID- 8262085
TI  - The link between acute haemodynamic adrenergic beta-blockade and long-term
      effects in patients with heart failure. A study on diastolic function, heart rate
      and myocardial metabolism following intravenous metoprolol.
AB  - The present study was performed to find possible mechanisms linking the early
      effects of beta-blockade with the observed long-term effects in patients with
      heart failure. In 57 patients with heart failure, 13 +/- 3.1 mg of metoprolol was
      given intravenously. The patients were investigated by invasive haemodynamics (n
      = 34), including collection of myocardial metabolic data during atrial pacing
      stress (n = 16), by radionuclide angiography during physiological atrial pacing
      (n = 13), and by a bedside evaluation (n = 10). Diastolic function, measured by
      early peak filling rate, followed changes in heart rate, but was similar when
      heart rate was held constant by atrial pacing before and after beta-blockade.
      Following beta-blockade and slower heart rates, diastolic filling volumes were
      redistributed to late diastole. Metoprolol induced a parallel decrease in
      coronary sinus flow and myocardial oxygen consumption. Myocardial oxygen
      consumption following beta-blockade decreased both during spontaneous rhythm (25
      +/- 15 to 16 +/- 8.8 ml min-1; P = 0.006), and during atrial pacing stress (30 +/
      13 to 23 +/- 11 ml.min-1; P = 0.004). Cardiac index decreased owing to reduction
      of heart rate (2.3 +/- 1.0 to 1.9 +/- 0.64 l.min-1.m2; P = 0.0003), while left
      ventricular filling pressure was unchanged. Ejection fraction and ventricular
      volumes were unaltered following atrial pacing or beta-blockade. There was a
      reflex increase in noradrenaline concentration after beta-blockade injection
      (0.96 +/- 0.66 to 1.20 +/- 0.91 nmol.l-1; P = 0.002), whereas myocardial
      noradrenaline overflow was unchanged. There was a trend towards an increase in
      myocardial lactate consumption after beta-blockade administration during atrial
      pacing stress. It is suggested that the surprisingly good tolerability seen after
      acute administration of beta-blockers to patients with severe heart failure may
      be explained by prolongation of the diastolic filling phase, which outweighs the
      negative inotropic effects. The reduced myocardial metabolic demand may allow the
      failing myocardium to recover and explain the excellent long-term effect on heart
      function following beta-blockade treatment.

PMID- 8262086
TI  - Coronary venous retroinfusion of felodipine reducing infarct size without
      affecting regional myocardial blood flow.
AB  - Effects on the ischaemic and reperfused myocardium of felodipine, a vasoselective
      calcium blocker, retrogradely infused into the coronary vein was investigated in
      a porcine model. Sixteen open-chest pigs underwent 45 min of myocardial ischaemia
      by occlusion of the left anterior descending coronary artery followed by 4 h of
      reperfusion. Either felodipine (felo-retro group, 7 nmol.kg-1: n = 6) or the
      corresponding amount of vehicle (vehicle group: n = 5) was retroinfused over 30
      min starting 5 min prior to reperfusion. In a third group, the same amount of
      felodipine was administered intravenously (felo-i.v. group n = 5). Myocardial
      regional blood flow was measured with radioactive microspheres prior to ischaemia
      and at different times of reperfusion. Infarction size, expressed as a percentage
      of the area at risk, was significantly reduced to 62 +/- 12% in the felo-retro
      group as compared to 86 +/- 12% (P < 0.05) and 94 +/- 5% (P < 0.05) in the
      vehicle and felo-i.v. group, respectively. Following an early hyperaemia, the
      regional blood flow decreased uniformly in the reperfused myocardium in all three
      groups and there were no significant differences between the groups at any period
      of reperfusion. In conclusion, felodipine retroinfused into the coronary vein
      could salvage ischaemic and reperfused myocardium without affecting the regional
      blood flow. The mechanism of this protective effect should be explained by
      factors other than an increased myocardial blood flow during reperfusion.

PMID- 8262088
TI  - Sequential changes in sympatho-neuronal regulation and contractile function
      following aortic regurgitation in rabbit heart.
AB  - This study was designed to determine the sequential changes in sympatho-neuronal
      regulation and contractile function of hearts exposed to volume overloading.
      Aortic regurgitation was produced by perforation of the aortic valve in 20
      rabbits. Another 20 rabbits underwent sham operation. They were randomly assigned
      to a 1-day group, a 1-week group, and a 4-week group. Haemodynamics, myocardial
      beta-adrenoceptor binding number and catecholamines were measured in each period
      after production of aortic regurgitation. Left ventricular end-diastolic pressure
      increased and cardiac output decreased progressively over the week following
      production of aortic regurgitation, but they returned towards normal during the
      subsequent 3 weeks. Left ventricular free wall thickness increased 4 weeks after
      production of aortic regurgitation, and plasma norepinephrine increased 1 day
      after the procedure. Maximal binding sites of myocardial beta-adrenoceptors (125I
      iodocyanopindolol) were decreased 1 day and 1 week after production of aortic
      regurgitation. Myocardial norepinephrine was also reduced. After 4 weeks, both
      beta-adrenoceptor binding sites and myocardial norepinephrine content were
      restored. Alterations in sympatho-neuronal regulation are related to the
      compensatory processes in volume overloaded hearts.

PMID- 8262087
TI  - Excimer laser-induced vasoreactivity.
AB  - Earlier generations of excimer lasers, designed for industrial or non
      cardiovascular medical applications, have been previously shown consistently to
      induce vasorelaxation of vascular smooth muscle in vitro. Such lasers were
      typically characterized by pulse durations of < or = 15 nanoseconds (ns). Excimer
      lasers currently employed for cardiovascular applications were designed with
      longer pulse durations (up to 220 ns) to facilitate fibreoptic transmission.
      Because arterial spasm has been observed in patients undergoing percutaneous
      revascularization with such lasers, we investigated the effect of so-called
      'stretched pulse' excimer laser irradiation on vasomotor reactivity. A total of
      69 rings of aorta harvested from New Zealand white rabbits were mounted
      isometrically in Krebs buffer solution and exposed to 308 nm from an excimer
      laser with a pulse duration of 120 ns. Fifty rings were exposed without
      pharmacological pre-treatment. The remaining 19 rings were exposed after
      pharmacological pre-treatment: 11 were precontracted with norepinephrine (NE, 10(
      9)-10(-5) M), while eight were irradiated in Ca(2+)-free buffer after pre
      relaxation with nitroglycerin (NTG, 7 x 10(-5) M). Without pharmacological pre
      treatment, the vasomotor response to the excimer laser was variable:
      vasoconstriction was observed in 27 rings (16.1 +/- 0.8% (mean +/- SEM) of
      response to 5-HT), vasorelaxation in 21 rings (43.2 +/- 17.0% of response to 5
      HT), and a heterogeneous response (vasoconstriction 4.9 +/- 1.0%, vasorelaxation
      12.9 +/- 0.3%) in two rings. The vector of vasomotor response in non
      precontracted rings was not predicted by fluence, frequency or temperature rise.
      A consistent vasomotor response was recorded only when pharmacological pre
      treatment was employed. Among 11 rings pre-contracted with NE, the excimer laser
      produced vasorelaxation in 34/34 (100%) exposures; in contrast, among eight rings
      pre-relaxed with NTG in Ca(2+)-free buffer, the excimer laser produced
      vasoconstriction in 40/40 (100%) exposures. For all rings, including pre
      contracted, pre-relaxed and those which were not pharmacologically pre-treated,
      the vector of vasomotor response was endothelium-independent. The magnitude of
      all vasomotor responses, including vasoconstriction in non-precontracted rings,
      could be diminished by limiting the duration of exposure. Thus, in contrast to
      the earlier generation, short-pulse excimer lasers, long pulse-duration excimer
      lasers in current clinical trials produce an unpredictable, heterogeneous
      vasomotor response. This in-vitro finding is consistent with the unpredictable
      development of vascular spasm in patients undergoing excimer laser angioplasty.
      Furthermore, these findings support the concept of employing abridged pulse
      trains to diminish the likelihood of laser-induced vasoconstriction during
      excimer laser angioplasty.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8262089
TI  - Ischaemia induced alternans of action potential duration in the intact-heart:
      dependence on coronary flow, preload and cycle length.
AB  - Clinical and experimental evidence relate action potential duration (APD)
      alternans to ischaemic heart disease and ventricular arrhythmias. The present
      investigation was performed to study the quantitative relationship between APD
      alternans and the degree of ischaemia, loading conditions and cycle length (CL)
      in an intact heart. Monophasic action potentials (MAP) were simultaneously
      recorded by contact electrodes from two left (LV) and one right ventricular (RV)
      sites in 20 Langendorff-perfused rabbit hearts. The preparations were subjected
      to global ischaemia at flow rates ranging from 40% of normal flow to complete
      cessation of flow. Pacing was performed at either constant or regularly changing
      CL. The magnitude of APD alternans was expressed as beat-to-beat differences in
      action potential duration of two consecutive MAPs. During normal perfusion,
      neither very fast pacing at a CL of 200 ms nor periodical rate switches resulted
      in persistent APD alternans. Pacing at a constant CL of 800 ms did not induce APD
      alternans at complete cessation of flow for 6 min. However, alternans developed
      progressively at a constant CL of 400 ms after 2.8 +/- 0.3 min of complete
      ischaemia at the pre-loaded LV, and after 4.6 +/- 0.4 min at the unloaded RV (P <
      0.01). The reduction of preload at the LV from 15 to 5 mmHg end-diastolic
      pressure delayed development of APD alternans from 2.8 +/- 03 min to 4.3 +/- 0.4
      min (P < 0.05) at 400 ms CL. Following graded underperfusion of 40%, 20% and 10%
      of initial flow, persistent APD alternans developed in relation to the degree of
      flow reduction and increased progressively with duration of ischaemia. APD
      alternans at the LV always preceded the onset of APD alternans at the RV. In
      experiments with identical flow rates the shortest CL of 200 ms resulted in the
      greatest and earliest initiation of APD alternans compared to the longer CL (P <
      0.01, P < 0.001). An increase in CL from 400 to 800 ms immediately abolished APD
      alternans, generated by the shorter CL, at any time during the 6 min period of
      complete ischaemia. Similarly, increasing the cycle length from 200 or 400 to 600
      ms eliminated APD alternans up to 6 min of ischaemia and significantly reduced
      its magnitude between 7 and 10 min within a few beats. We conclude that
      persistent APD alternans is a characteristic findings in the rabbit heart during
      global ischaemia4 It is a sensitive parameter of the severity of ischaemia and
      depends.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8262090
TI  - Effect of site, summation and asynchronism of inputs on atrioventricular nodal
      conduction and refractoriness.
AB  - The impulses coming from the sinus node synchronically penetrate the AV node via
      the crista terminalis and inter-atrial septum. Studies in superfused rabbit AV
      preparations suggest that the crista terminalis is a more effective input than
      the inter-atrial septum, and that the summation of both inputs facilitates AV
      nodal conduction. The aim of this study was to verify the hypothesis in a more
      physiological model, such as the whole rabbit heart perfused by a Langendorff
      system. Fifteen rabbit hearts were studied in a Langendorff perfusion system with
      six bipolar extracellular electrodes: two for stimulating (crista terminalis and
      inter-atrial septum) and four for recording (crista terminalis, inter-atrial
      septum, His bundle electrogram and right ventricle). Seven hearts (Group I) were
      consecutively paced at the crista terminalis, inter-atrial septum and both sites
      simultaneously, to determine the AV nodal Wenckebach cycle length and effective
      refractory period under basal conditions and after acetylcholine (0.75 x 10(-6)
      M). In eight hearts under 0.75 x 10(-6) M acetylcholine (Group II), the crista
      terminalis and inter-atrial septum were simultaneously (delay = 0 ms) or
      sequentially (delay = 2, 4, 6, 8, 10, 12, 14, and 16 ms) stimulated to calculate
      the AV nodal effective refractory period and the AH interval at an atrial
      coupling interval 5 ms longer than the AV nodal effective refractory period, for
      each delay tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262091
TI  - Treatment of atrial fibrillation. Recommendations from a workshop arranged by the
      Medical Products Agency (Uppsala, Sweden) and the Swedish Society of Cardiology.
AB  - Atrial fibrillation may be paroxysmal or chronic. The paroxysmal form presents in
      the form of attacks of short duration but may last for up to 3-4 days. Episodes
      of atrial fibrillation of longer duration are considered as chronic. The
      diagnosis is made by ECG.

PMID- 8262092
TI  - Infected right atrial thrombus--a complication of a central venous catheter.

PMID- 8262093
TI  - Coronary angioplasty: is cardiological practice in the U.S.A. really the gold
      standard for Europe?

PMID- 8262094
TI  - Giant cell myocarditis in a transplanted heart.

PMID- 8262095
TI  - Fetal monitoring during maternal antiarrhythmic therapy.

PMID- 8262096
TI  - Treatment of recurrent pericarditis with colchicine before using corticosteroids.

PMID- 8262097
TI  - Antimicrobial prophylaxis in urologic surgery: does it give some benefit?
AB  - Three types of antibiotic prophylactic regimens were evaluated versus a control
      without prophylaxis (group A: 3,912 cases) in urologic surgery. The antibiotic
      regimens were: group B = cefazolin 1 g/12 h/3 days (3,660 cases); group C =
      cefonicid 1 g/24 h/3 days (2,076 cases), and group D = cefonicid 1 g single dose
      (3,169 cases). The parameters used were the comparison of the corresponding rates
      of postsurgical sepsis and operative wound infections. Numeric investigations for
      the validity of a retrospective study (unpaired data) were performed:
      homogenicity test, relative risk point estimate and confidence limits (95%), and
      etiological fraction point estimate and confidence limits (95%). Chi-square for
      other purposes were performed. Endoscopic handling was considered homogeneous
      (same infective risk), while open surgery was heterogeneous (p < 0.001). In order
      to avoid probable bias, a correction factor was used. Although in different
      degrees, prophylaxis significantly reduced the morbidity of surgical wound
      infections (p < 0.001; etiological fraction > 90%). The differences (p < 0.01)
      between groups B and C/D were attributed to pharmacokinetic causes (short T 1/2
      of cefazolin). To obtain the maximum protective effect, the use of antibiotics
      with a T 1/2 of > 4 h is suggested. There was no resistant mutans in previously
      sensitive strains. However, a significant selection of intrinsically resistant
      strains was observed. Monodose offers at lest the same advantages as multiple
      dose therapy. In addition, the monodose selected in a lesser proportion both the
      resistant strains (p < 0.001) and the number of microbial associations (p <
      0.01).

PMID- 8262098
TI  - Seminal vesicle congestion as a cause of postprostatectomy dysuria.
AB  - A series of benign prostatic hypertrophy patients were routinely evaluated,
      including transrectal echography, before and at regular intervals following
      surgery. Five patients had persistent symptoms of dysuria at 14-30 months after
      surgery. There was no infection, residual urine or malignancy to explain their
      symptoms. The seminal vesicles (SVs) were severely dilated on transrectal
      echography, a finding which was definitely not present on initial examination.
      The patients were treated by transrectal echo-guided aspiration of the SVs by the
      perineal approach. The fluid aspirated was examined, and antibiotics were
      directly injected into the SVs. In 4 of the patients, there was a dramatic relief
      of symptoms with prolonged improvement. In only 1 case, following transurethral
      resection, there was but slight improvement. Dilated, obstructed SVs after
      prostatectomy, clearly diagnosed on transrectal echography, may be the cause of
      persistent irritative urinary symptoms. Treatment can be instituted by echo
      guided aspiration of the fluid with simultaneous injection of a potent
      antibiotic, resulting in probable immediate relief.

PMID- 8262099
TI  - Downstaging of stage C prostatic carcinoma by inductive chemo-hormonal therapy?
AB  - One hundred and three patients with clinical stage C prostatic carcinoma
      (palpable extra-organ extension) underwent inductive chemo-hormonal treatment
      followed by radical retropubic prostatectomy with pelvic lymphadenectomy. First a
      careful noninvasive tumor staging was performed, which included a thorough
      digital rectal palpation, PSA, PAP, chest X-ray, bone scan, IVP, transabdominal
      and transrectal ultrasonography, CT and MRI. Then inductive chemo-hormonal
      therapy commenced. It consisted of total androgen deprivation plus the
      administration of cDDP or 5-FU + calcium folinate + mitomycin. After completion
      of chemotherapy (i.e. 4 months later), noninvasive staging was repeated. Then
      radical prostatectomy was carried out, followed by histologic work-up of the
      specimen. Postinductive, noninvasive examinations showed clinical downstaging in
      49 of the original 103 patients (47.5%). Histopathology showed confinement of the
      tumor to the prostate in 40 specimens (38.8%). These results prove that chemo
      hormonal induction is highly effective and suggest strongly but do not prove
      definitely histological downstaging in a significant percentage of the patients.

PMID- 8262100
TI  - Cystectomy and urinary diversion during twenty years--complications and metabolic
      implications.
AB  - A retrospective analysis of 130 cases of cystectomy and urinary diversion for
      bladder carcinoma was performed. A logistic regression analysis found
      preoperative irradiation to be associated with early complications (p = 0.014),
      whereas no such association was observed with late complications. Metabolic
      evaluation in 51 surviving patients revealed hyperchloremia in 17 patients (33%)
      and hyperchloremic acidosis in 2 cases (4%). Vitamin B12 deficiency was found in
      11 patients (22%), all of whom had preoperative irradiation or reservoir
      procedures performed. Routine evaluation of vitamin B12 serum levels should be
      carried out at follow-up in these groups of patients.

PMID- 8262102
TI  - Do not treat staghorn calculi by extracorporeal shockwave lithotripsy alone!
AB  - A review of 84 patients with triple phosphate (staghorn) calculi treated by
      extracorporeal shockwave lithotripsy (ESWL) revealed a 67% stone clearance at 6
      months. Classification of calculi according to morphology showed a variation in
      stone clearance from 47 to 82%. A significant number of patients developed
      complications (25%) or required additional procedures (27%). ESWL monotherapy is
      not a suitable treatment option for most patients with staghorn calculi.

PMID- 8262101
TI  - Quantitative changes in platelet counts following major urological pelvic
      surgery.
AB  - Postperative quantitative changes in platelet counts have been reported following
      various extensive surgical procedures. It is generally accepted that reactive
      thrombocytosis at levels less than 1,000,000/mm3 is a benign condition and is not
      associated with increased risk of postoperative thrombohemorrhagic complications.
      The role of prophylactic treatment with platelet inhibitors in these situations
      is controversial. We assessed retrospectively the timing and the extent of
      postoperative thrombocytosis in 85 consecutive patients following major
      urological pelvic surgery and evaluated its possible clinical significance to
      hemorrhagic and thromboembolic complications, in view of the coincidence of
      multiple potential risk factors for thromboembolism in these patients. 73 (85.9%)
      patients demonstrated marked postoperative changes of platelet counts. In 12
      patients (14.1%) we found only minor fluctuations in platelet counts throughout
      the postoperative period. Two distinct groups of 26 and 47 patients respectively
      could be identified among these 73 patients, who differed in the rate and extent
      of changes in platelet counts. Those fluctuations were characterized by an early
      decrease in platelet levels (mean percentage change of 40 and 60% in groups I and
      II respectively). This was followed by a gradual increase leading to delayed
      thrombocytosis (mean percentage change of 225 and 305% in groups I and II
      respectively). Thromboembolic complications were diagnosed in 5 patients. The
      occurrence of thromboembolism preceded any significant increase in platelet
      counts in all 5 patients. There was no correlation between the timing of
      thromboembolic complications and timing and extent of the change in platelet
      count. We conclude that reactive thrombocytosis following major urological pelvic
      surgery is a frequent innocuous finding and is not associated with hemorrhagic or
      thromboembolic complications.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262103
TI  - Single potential analysis of cavernous electrical activity. Four years'
      experience in more than 500 patients with erectile dysfunction.
AB  - Since the recent introduction of cavernous electromyography by Gerstenberg and
      Wagner, a new too for the study of erectile dysfunction in man is available. The
      refinement of this method, single potential analysis of cavernous electrical
      activity (SPACE), offers a straightforward approach to the diagnosis of cavernous
      autonomic neuropathy and smooth muscle myopathy by minimal invasive means. SPACE
      was done in more than 500 consecutive patients with erectile dysfunction and in
      85 normal control subjects. With increasing experience the methodology was
      refined with respect to the used hardware as well as cut-off frequencies. In
      normal control subjects, SPACE showed a reproducible regular activity with
      potentials of low frequency and electrical silence inbetween. The potentials were
      synchronous throughout the cavernous bodies. In patients with peripheral
      autonomic denervation, asynchronous potentials with higher frequencies and
      irregular shape were found. Normal and abnormal potentials were found in patients
      with upper spinal cord lesions. Recordings obtained with surface electrodes
      showed similar characteristics when compared with recordings obtained with needle
      electrodes. Recent studies show that SPACE provides independent information about
      the autonomic and myogenic intactness of the cavernous tissue. Currently, a
      computerized expert system and a graded classification for easier interpretation
      is being developed with first results. We conclude that cavernous electrical
      activity can be recorded. SPACE is a reproducible diagnostic tool for erectile
      dysfunction.

PMID- 8262104
TI  - Vasopressin deficiency in primary nocturnal enuresis. Results of a controlled
      prospective study.
AB  - The lack of circadian rhythmicity of plasma arginine vasopressin (AVP) in primary
      nocturnal enuresis (PNE) in some children is known. The original test protocol is
      time-consuming and needs excellent compliance by children and parents. The goals
      of the presented study are the introduction of a simple screening test and the
      evaluation of the response of treatment using intranasal synthetic vasopressin.
      Fifty-five children (aged 8.2 +/- 3.1 years) with PNE and 15 children (aged 7.9
      +/- 2.4 years) of a control group were investigated. Using a standardized
      protocol, AVP levels were measured by radioimmunoassay (RIA) under controlled
      water intake 3 times per day over a period of 72 h. Fourteen of 55 tested
      children (25.5%) with PNE had a significant decrease in nocturnal AVP when
      compared to the control group. We measured also an increased nocturnal urine
      volume and a lower urine osmolality in this enuretic group. Eight of 14 patients
      (57.1%) with plasma AVP deficiency (AVPD) also had bladder instability. Nine of
      14 patients (64.3%) with AVPD with or without concomitant bladder instability
      were totally dry during desmopressin treatment, but only 2 (14.3%) remained dry
      after discontinuation of treatment. Our data suggest that nocturnal urine
      osmolality measurement may reflect AVPD and predict a positive treatment outcome.

PMID- 8262105
TI  - Urethral injuries in girls with pelvic trauma.
AB  - Three girls with major urethral injuries following motor vehicle accidents are
      presented. Early diagnosis of this rare condition, which is often associated with
      vaginal injuries, is imperative and a cystourethrogram, examination under
      anesthesia and a cystovaginoscopy are usually indicated. Primary repair of these
      injuries is recommended and long-term follow-up is essential.

PMID- 8262106
TI  - Effect of different types of textiles on sexual activity. Experimental study.
AB  - The effect of wearing different types of textiles on sexual activity was studied
      in 75 rats which were divided into five equal groups: four test groups and one
      control. Each of the four test groups were dressed in one type of textile pants
      made of either 100% polyester, 50/50% polyester/cotton mix, 100% cotton or 100%
      wool. Sexual behaviour was assessed before and after 6 and 12 months of wearing
      the pants and 6 months after their removal. The rate of intromission to mounting
      (I/M) was determined. The electrostatic potentials generated on penis and scrotum
      were also measured by electrostatic kilovoltameter. At 6 and 12 months of wearing
      the polyester and polyester-cotton mix pants, the I/M ratio was significantly
      reduced compared to the pre-test levels and the controls (p < 0.0001). The
      reduction was more manifest in the polyester than in the polyester-cotton mix
      group, and at the 12th month than at the 6th month of examination. The I/M ratio
      of the cotton and wool groups showed insignificant changes (p > 0.05) at the 6th
      month of the study and a significant increase at the 12th month (p < 0.01). Six
      months after removal of the pants, the I/M ratio returned to the pre-test levels
      (p > 0.05) in the four groups. The polyester-containing pants generated
      electrostatic potentials while the other textiles did not. These potentials seem
      to induce 'electrostatic fields' in the intrapenile structures, which could
      explain the decrease in the rats' sexual activity.

PMID- 8262107
TI  - New aspects on the composition, structure and origin of calcium oxalate
      monohydrate calculi.
AB  - In this paper a thorough study on the composition and structure of calcium
      oxalate monohydrate (COM) papillary calculi is presented. In 86.4% of these
      calculi, small amounts of phosphates were detected and generally located at the
      calculi core. This demonstrates the importance of phosphates as the heterogeneous
      nucleus of 'pure' COM calculi. Study of the main biochemical parameters of these
      patients showed that the most frequent biochemical alteration was associated with
      hypocitraturia (25%), whereas hypercalciuria and/or hyperoxaluria were detected
      in very few cases. With respect to the urinary pH values, 70% of the patients
      presented values lower than 6 and 30% higher than 6. These facts indicate that in
      a number of cases the formation of phosphates is not the result of persistent
      high urinary pH values, and the presence of occasional papillary microinfections
      must be suspected. It is clear that, by avoiding the formation of heterogeneous
      phosphate nuclei, 'pure' COM calculi would not develop, and consequently
      therapies for these individuals under these conditions must take this into
      account.

PMID- 8262108
TI  - Circadian periodicity of urinary inhibitor of calcium oxalate crystallization in
      healthy Indians and renal stone formers.
AB  - The inhibitory activity (IA) of calcium oxalate crystallization was investigated
      in healthy Indians and renal stone formers. A marked circadian rhythm was
      observed in men and women of both groups. The rhythm pattern was similar on the
      basis of sex; however, it was different in stone formers as compared to normals.
      The acrophase for crystallization of calcium oxalate was observed, respectively,
      at 05.43 and 05.52 h in healthy men and women, and at 09.52 and 09.23 h in male
      and female renal stone formers. Moreover, the acrophase of percent inhibition by
      IA was observed at 17.44 and 17.52 h in healthy participants and at 21.52 and
      21.27 h in male and female stone formers, respectively. Therefore, the acrophase
      suggests a highest risk of crystallization during the morning hours and a minimum
      one during the evening hours. The day-night rhythmic pattern of urinary calcium,
      magnesium and phosphorus is discussed in relation to the rhythm of IA.

PMID- 8262109
TI  - S100a0 protein as a marker for tissue damage related to extracorporeal shock wave
      lithotripsy.
AB  - We assayed serum and urine S100a0 protein levels in patients with renal stones (n
      = 21) or ureteral stones (n = 18), before and after extracorporeal shock wave
      lithotripsy (ESWL) to evaluate tissue injury. Serum S100a0 protein levels
      increased significantly immediately after, and at 2 and 24 h after ESWL in
      patients with renal stones, and at 2 and 24 h after ESWL in patients with
      ureteral stones. Significant increases in urine S100a0 protein levels were
      observed immediately and 2 h after ESWL in both groups of patients. The patients
      receiving a higher number of shock waves had a more pronounced increase in serum
      S100a0 protein especially in the case of more than 3,500 shock waves. Because
      S100a0 protein exists at relatively high concentrations in the proximal renal
      tubules and skeletal muscles, serum and urine S100a0 protein levels appear to be
      useful markers of tissue injury, including damage in the kidney and skeletal
      muscles, in the early post-ESWL phase.

PMID- 8262110
TI  - Neuron-specific enolase: a serum tumor marker in renal cell carcinoma?
AB  - In previous reports, neuron-specific enolase (NSE) has been considered to be a
      useful tumor marker in renal cell carcinoma (RCC). This led us to perform a
      prospective clinical trial in this field. NSE was checked as a tumor marker for
      diagnosis and monitoring of patients with RCC. We report on 55 patients and their
      NSE level before and after radical nephrectomy and correlated the serum level of
      NSE to immunohistological staining and clinical stage of nephrectomy specimens.
      In contrast to other researchers, our results on NSE as a tumor marker in RCC are
      disappointing.

PMID- 8262111
TI  - Transurethral needle ablation (TUNA) of the prostate using low-level
      radiofrequency energy: an animal experimental study.
AB  - Transurethral needle ablation of the canine prostate using low level
      radiofrequency energy was examined for efficacy and safety in a two-stage
      experimental study. Eleven mongrel dogs were treated via the bladder neck and
      prostatic urethra using a specially designed catheter through which needle
      antennas were advanced into the prostatic tissue. A radiofrequency energy source
      was connected to the catheter and used to create tissue ablation. In the first 5
      dogs this was found to be feasible. Necrotic lesions were created around the
      needle antennas. Typically, lesions were 1 cm in diameter and conical in shape.
      The actual size of the lesion was directly related to power level used, time of
      ablation and length of needle deployment. In the next 6 dogs temperatures were
      simultaneously measured in the prostatic urethra and rectum. The dogs were
      sacrificed 0, 2, 2, 14, 28 and 30 days following the experiments and the bladder,
      prostate and anterior rectal wall were removed en bloc and examined
      macroscopically and histopathologically for any changes. It was found that
      urethral temperatures increased to 46.1 degrees C on the average while rectal
      temperature did not rise during the entire experiment. The lesions found in the
      prostate were similar to those found in the first 5 dogs. No macroscopic or
      histopathologic changes were noted at the bladder base, anterior rectal wall or
      in the distal prostatic urethra. It was concluded that prostatic tissue ablation
      in the canine model can be achieved safely and could justify the start of human
      trials.

PMID- 8262112
TI  - Extracorporeal repair of primary renal artery dissection.
AB  - Four cases of isolated dissection of the renal artery were diagnosed and treated
      in our institution. In 2 cases, angiography showed dissection of the left renal
      artery with involvement of peripheral branches; in 1 case, the dissection
      involved the right renal artery with complete occlusion of an upper-pole branch
      and upper-pole infarction, and 1 patient presented a bilateral dissection,
      limited to the main trunk on the right side and involving prepelvic and
      retropelvic branches on the left side. Surgical treatment consisted in renal
      autotransplantation in the iliac fossa after extracorporeal reconstruction of the
      arterial pedicle. The results were encouraging with normalization of blood
      pressure and improvement of renal function in all cases.

PMID- 8262113
TI  - Mixed gonadal dysgenesis associated with unilateral cavernosal fibrosis and
      presenting as a cystic lower abdominal mass.
AB  - We report the first case of a patient suffering from mixed gonadal dysgenesis and
      fibrosis of the left cavernous body. The patient who complained about erectile
      dysfunction had received a penile prosthesis and was diagnosed 3 years after
      surgery when internal rudimentary gonads presented as a lower abdominal mass.

PMID- 8262114
TI  - Utricular cyst: a cause of recurrent urinary tract infection.
AB  - The case of a 21-year-old man suffering from recurrent urinary tract infections
      due to a contaminated utricular cyst is presented. The patient was cured by
      transrectal puncture of the cyst. Especially in younger patients, initial
      conservative therapy is advisable. To exclude prostatic cysts as a possible
      cause, evaluation of recurrent urinary tract infections in men should include
      diagnostic imaging of the prostate.

PMID- 8262115
TI  - Quality of life in prostatic carcinoma.
AB  - Subjective quality-of-life assessments obtained from investigators and patients
      were compared in a subset of 76 patients from an EORTC study (protocol 30853) on
      metastatic prostatic carcinoma. In this study the therapeutic effect of
      orchiectomy was compared with a luteinizing hormone-releasing hormone analogue
      depot preparation and flutamide in 327 patients in total. Pretreatment, 6- and 12
      month quality-of-life assessments revealed large variations between the patients'
      and the investigators' evaluation of performance status and sexual status
      (potency). Correlation analysis showed that reduced social life, impaired sexual
      potency and fatigue played important roles in overall psychological well-being.
      It was concluded that quality-of-life assessments obtained by self-administration
      questionnaires is a feasible approach and provides a tool to evaluate the
      benefits of treatment in prostate cancer.

PMID- 8262116
TI  - Quality of life of patients with advanced and metastatic prostatic carcinoma.
AB  - The quality of life of patients with advanced prostate cancer may be profoundly
      affected by local infiltration into adjacent organs and the occurrence of distant
      metastases. Secondary manifestations of advanced stages of prostate cancer
      include urinary retention, ureteric obstruction, rectal obstruction, chronic bone
      pain, compression of the spinal cord, hematological dysfunction and metabolic
      abnormalities. This review discusses the management of these patients in order to
      optimize their quality of life. Suitable palliative treatment for each secondary
      manifestation is recommended.

PMID- 8262117
TI  - Staging and prognosis of prostate cancer.
AB  - The tumor node metastasis (TNM) classification is the universal staging system
      for malignant tumors. The 1992 revised TNM classification for prostate cancer is
      presented and reviewed. The trend from an anatomical to a biological
      classification is supported by the development of this classification and the
      definition of prognostic factors. Histological grade is already accepted into the
      classification for adenocarcinoma, but restricted to the stage grouping. Other
      prognostic factors will be added to the scheme in a separate axis after
      multivariate analysis and confirmation of their value in randomized trials.
      Progress in prognosis depends on proper selection and validation of prognostic
      factors. Revalidation in prospective trials is, therefore, needed and justified.

PMID- 8262118
TI  - Laparoscopic pelvic lymphadenectomy in the staging of prostate cancer.
AB  - Lymphadenectomy provides sufficiently accurate information for the efficient
      staging of prostatic carcinoma. This paper provides a step-by-step guide to
      laparoscopic lymphadenectomy, based on the authors' experiences. Clinical staging
      of patients with neoplastic node involvement was also documented. Laparoscopic
      lymphadenectomy was found to be a highly efficient method for nodal staging of
      pelvic neoplastic pathology, similar to that reported in conventional surgery.
      The mean number of nodes obtained per case was determined to be 11.2. Of the 35
      cases in which laparoscopic lymphadenectomy was performed, node involvement was
      evident in 23%, all of whom were negative by computerized tomography scan.
      Laparoscopic lymphadenectomy was concluded to be a minimally invasive surgical
      procedure, associated with few complications and a short hospital stay.

PMID- 8262119
TI  - Workshop summary: screening policies and procedures.
AB  - The question of screening for prostate cancer has, since the advent of prostate
      specific antigen testing, become a major source of contention. Important issues
      include: (1) should such screening become part of routine health checks for men;
      (2) if routine screening is implemented, at what age should it be started, and
      (3) can the early detection of prostate cancer facilitated by such screening
      actually benefit the patient in the long run? These were some of the topics put
      to the audience and debated by the panel of experts in the discussion forum on
      screening.

PMID- 8262120
TI  - Radical prostatectomy or wait-and-watch?
AB  - With intensified screening and the use of new diagnostic tools for prostate
      cancer (prostate-specific antigen, rectal ultrasound, magnetic resonance imaging
      with rectal coils, etc), the number of newly diagnosed cases of prostate cancer
      is rising rapidly, whereas the frequency of death due to prostate cancer remains
      almost stable. It must therefore be assumed that the number of patients in whom a
      diagnosed prostate cancer will not be fatal is also increasing. Consequently, not
      every prostatic carcinoma requires radical treatment when diagnosed. Also, it
      must be concluded that not every man who is a long-term survivor after radical
      prostatectomy owes his survival to the treatment. Long-term survivorship may
      reflect the relatively benign biological potential of this disease in an
      individual patient. Therefore, there is an inherent risk of overtreating patients
      and this must be weighed against the costs, the postoperative morbidity and the,
      albeit low, mortality of a radical prostatectomy. Nevertheless, as long as we do
      not have diagnostic tools which, at an early stage of prostate cancer, enable us
      to determine whether a carcinoma will ultimately have a fatal outcome, we are
      obliged to offer radical prostatectomy to younger patients (who have a life
      expectancy of more than 10 years) as long as they have organ-confined disease.

PMID- 8262121
TI  - Transcoccygeal radical prostatectomy for localized prostate cancer: early
      clinical results.
AB  - Twelve patients with adenocarcinoma of the prostate underwent radical
      transcoccygeal prostatectomy. The methodology and outcome are described.
      Preoperative laparoscopic lymphadenectomy was performed on all patients. The
      average operative time for the prostatectomy using the transcoccygeal route was 3
      h and 7 min, and no major postoperative complications occurred. Compared to the
      classic retropubic approach, preservation of the neurovascular bundles and
      urethral anastomosis seemed to be facilitated. It was concluded that radical
      prostatectomy can be performed safely using the transcoccygeal approach.

PMID- 8262122
TI  - Radical perineal vs. retropubic prostatectomy: a review of optimal application
      and technical considerations in the utilization of these exposures.
AB  - Radical prostatectomy can be performed either with a retropubic or perineal
      approach. While the former has enjoyed popularity in recent years, perineal
      prostatectomy has undergone a substantial resurgence because of interest in
      laparoscopic pelvic lymphadenectomy. The advantages and disadvantages of each are
      defined, as well as technical modifications that have been developed seeking to
      diminish problems with each approach. While many urologic surgeons are no longer
      familiar with the perineal approach, its potential advantages, particularly in
      certain situations, would suggest that it can be a valuable component of the uro
      oncologist's surgical armamentarium for the management of localized prostate
      cancer.

PMID- 8262123
TI  - Perspectives on the role of radiotherapy in organ-confined and locally advanced
      prostate cancer.
AB  - Radiotherapy is an effective management option in the treatment of organ-confined
      prostate cancer with survival results and local control possibilities similar to
      those of surgery. Although radiotherapy is used in locally advanced (stage-C)
      prostate cancer, there are significant developments that may make treatment more
      effective, such as hormonal cytoreduction, neutron radiotherapy and conformal
      therapy.

PMID- 8262124
TI  - Workshop summary: approaches to radical prostatectomy.
AB  - The retropubic approach has recently become the method of choice for radical
      prostatectomy. This has been particularly evident since the 1970s, when open
      staging lymphadenectomy became an important part of the diagnostic workup, as
      both procedures could be carried out concurrently via the anterior approach.
      However, the development and rapidly increasing use of laparoscopic
      lymphadenectomy may signal a return to the perineal approach in certain cases.
      Alternatives to radical prostatectomy, including radiotherapy and interstitial
      brachytherapy, may also have their place. The audience was asked to comment on
      their own practices and the factors that would influence their decisions.

PMID- 8262125
TI  - Adjuvant hormonal therapy following radical prostatectomy.
AB  - The benefit of adjuvant treatment after radical prostatectomy in patients with
      extracapsular or node-positive disease is still being evaluated. In a
      retrospective study of 293 patients undergoing radical prostatectomy, 86 patients
      received adjuvant treatment. The median follow-up time was 4.1 years (range 3
      months to 16 years). Forty-five patients progressed, and 27 patients died cause
      specifically. Calculating the time to progression and the cause-specific survival
      as study endpoint, the control group showed significantly better results than the
      adjuvantly treated group, owing to an imbalance of pathological stage between the
      2 groups. The stage-correlated analysis of stage pT3 pN0 tumors according to
      adjuvant therapy showed no benefit in time to progression or survival for the
      adjuvant-treated patients. Similar results were also found for patients with
      positive pelvic lymph nodes. In this group adjuvant therapy again had no impact,
      either on time to progression or survival. At the present time, no rationale
      exists to call for categorical adjuvant treatment in patients with positive lymph
      nodes or extracapsular disease.

PMID- 8262126
TI  - Dilemma of microscopic lymph node metastases in human prostate cancer.
AB  - During radical surgical procedures for prostatic carcinoma, lymph node metastases
      are not infrequently discovered unexpectedly. Microscopic lymph node metastases,
      on the other hand, are generally overlooked and identified first by routine
      histology following surgery. In both these situations there is some controversy
      about how to proceed therapeutically. When lymph node metastases are discovered
      during radical prostatectomy, many authors favor discontinuing surgery, which is
      associated with a high morbidity, and then start the patient on hormonal
      treatment. This approach, however, is not favored by all investigators. When
      microscopic lymph node metastases are reported, the complexity of the situation
      increases. The various dilemmas posed to urologists when confronted with lymph
      node metastases are discussed.

PMID- 8262127
TI  - Workshop summary: hormonal suppression in the neoadjuvant setting and advanced
      disease.
AB  - For advanced prostate cancer, hormonal suppression has long played an important
      role in patient management. Furthermore, the concept of combined androgen
      blockade using a luteinizing hormone-releasing hormone agonist in combination
      with an antiandrogen such as flutamide is gaining increasing acceptance. The
      novel regimen of finasteride (a 5-alpha-reductase inhibitor) plus flutamide may
      also have a role to play in the future. In the neoadjuvant setting, androgen
      suppression prior to radical prostatectomy is a novel approach. This strategy
      aims to reduce the size of the tumor as much as possible, hopefully downstaging
      the disease, and thus increasing the chances of a successful outcome at
      operation. Data from studies presented at this symposium revealed a clear
      reduction in tumor size by this method but the effects on both staging of disease
      and long-term outcome were not so definitive. Questions were put to the audience
      and the expert panel to assess their opinion of hormonal therapy and staging
      techniques, both in the neoadjuvant and advanced disease settings.

PMID- 8262128
TI  - Is the outcome of conservative management for localized prostate cancer
      acceptable? An overview.
AB  - The outcome of conservative management in a consecutive series of 107 localized
      prostate cancers (mean age 73.5 years) has been analyzed. Follow-up ranged from 1
      to 12 years. Following regular surveillance and no initial treatment, 3 died from
      prostate cancer with a median survival of 6.3 years compared to 34 who died from
      intercurrent disease with a median survival of only 2.6 years. The observed
      survival for the whole group was similar to the expected survival for an age
      matched population in Scotland. This was despite the fact that the nodal status
      and the capsular invasion were unknown.

PMID- 8262129
TI  - Overview of current status of total androgen deprivation in metastasized prostate
      cancer.
AB  - The incidence and methods available for the diagnosis of metastatic prostate
      cancer, together with the development and efficacy of various treatments, are
      discussed. In patients with good prognostic characteristics, maximal androgen
      deprivation, with blockade of both testicular and adrenal androgens, seems to be
      the favored approach. Surgical castration, although effective, seems inferior to
      depot luteinizing hormone-releasing hormone therapy with respect to patients'
      acceptance and preference. Nonsteroidal antiandrogens, such as flutamide, have
      advantages over steroidal compounds both in efficacy and side effects. Recent
      studies have demonstrated that combination therapy may be superior in terms of
      progression-free survival and overall survival in patients with metastatic
      prostate cancer.

PMID- 8262130
TI  - Total androgen blockade: the United States experience.
AB  - Maximal androgen blockade may improve the effectiveness of treatment of prostate
      cancer. To test this hypothesis we conducted a randomized, double-blind trial in
      patients with disseminated and previously untreated prostate cancer (stage D2).
      All patients (n = 603) received leuprolide, 1 mg/day s.c. in combination with
      either placebo (n = 300) or flutamide 250 mg p.o. t.i.d. (n = 303). The median
      progression-free survival times were estimated at 14 months for the leuprolide
      plus placebo group and 17 months for leuprolide plus flutamide patients: median
      times for overall survival were 29 vs. 35 months, respectively. Patients with
      minimal disease and good performance status did particularly well on combination
      therapy. Median progression-free survival for this subgroup was 19 months for
      leuprolide plus placebo patients vs. 48 months for patients on combined therapy
      (p = 0.035) Flutamide appeared to reduce the disease flare associated with
      leuprolide monotherapy. Combined androgen blockade with leuprolide and flutamide
      is superior to leuprolide treatment alone in patients with disseminated prostate
      cancer.

PMID- 8262131
TI  - Nonsteroidal antiandrogen monotherapy of metastatic cancer of the prostate.
AB  - The use of nonsteroidal antiandrogens as first-line therapy for the treatment of
      cancer of the prostate is discussed. The results of studies using flutamide as
      monotherapy are reviewed and show flutamide to be an effective agent in the
      treatment of metastatic prostate cancer. Comparative studies have shown that
      flutamide monotherapy is as effective as standard hormonal treatment, with no
      difference in the two treatments. In one study, treatment with diethylstilbestrol
      was found to be superior to flutamide in terms of survival. Further studies are
      required before the use of pure antiandrogen monotherapy can be recommended for
      the treatment of metastatic prostate cancer.

PMID- 8262132
TI  - Intracrinology: the basis for the rational design of endocrine therapy at all
      stages of prostate cancer.
AB  - Adrenal androgens contribute 40% of total androgens in adult men. The inactive
      precursor steroids dehydroepiandrosterone (DHEA) and DHEA-sulfate are secreted in
      large amounts by the adrenals and reach the prostate and other peripheral target
      tissues, where they are transformed into the potent androgen dihydrotestosterone
      (DHT). We have cloned and sequenced the cDNAs and/or genes which encode the
      enzymes responsible for the transformation of DHEA into DHT, namely 3 beta
      hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase, 17 beta-hydroxysteroid
      dehydrogenase and 5 alpha-reductase. Blockade of DHT synthesized by these
      enzymes, with a pure antiandrogen of the class of flutamide, prolongs life in
      advanced prostate cancer, the effect being much more important when a small
      number of metastases is present. Most importantly, 3-month combination therapy
      reduces cancer-positive margins at radical prostatectomy, from 38.5% in control
      patients to only 13% in those who received combination therapy. Combined with an
      efficient strategy for detection of early-stage prostate cancer, the present
      approach could offer the possibility of a cure to more than 80% of prostate
      cancer patients, compared with the present situation where a cure can be offered
      to less than 20% of patients, since the first diagnosis of prostate cancer is
      usually made at a late stage of the disease.

PMID- 8262133
TI  - Identification of two human Rho GDP dissociation inhibitor proteins whose
      overexpression leads to disruption of the actin cytoskeleton.
AB  - Proteins (IEF's 1120, 8118, 8120) sharing similarity to the bovine Rho GDP
      dissociation inhibitor (GDI) have been identified in the human two-dimensional
      gel database of keratinocyte proteins. Molecular cloning of the corresponding
      cDNAs showed that IEF 8118 is the human homolog of bovine GDI while IEF 8120 is a
      distinct although related protein. All available information indicates the IEF
      1120 is a derivative of IEF 8120. The cDNAs coding for IEF's 8118 and 8120 were
      recombined into vaccinia virus and expressed in differentiated human
      keratinocytes and their effect on the actin cytoskeleton was assessed by
      immunofluorescence using TRITC-phalloidin. The results showed that overexpression
      of both GDI proteins leads to rounding up of the cells and loss of stress fibers
      and focal contact sites. In addition, the cell to cell adhesion belts gradually
      disappeared, an effect that was particularly pronounced in infected cells
      overexpressing IEF 8120. Taken together, the results imply that Rho GDI's play a
      role in modulating the activity of the Rho proteins as their overexpression
      mimics phenotypic changes associated with the inactivation of these proteins.

PMID- 8262134
TI  - Selective loss of CDC2 and CDK2 induction by tumor necrosis factor-alpha in
      senescent human diploid fibroblasts.
AB  - Normal human diploid fibroblasts undergo a finite number of doublings in culture.
      This process of senescence is accompanied by a loss in the ability to respond to
      proliferative stimuli and is therefore distinct from the quiescent state induced
      by nutrient deprivation. We have studied changes in gene expression induced in
      these cells following exposure to the cytokine, tumor necrosis factor-alpha
      (TNF). We observed that TNF induced CDC2 and CDK2 expression in early-passage
      quiescent WI-38 fibroblasts. However, as cells approached senescence, their
      ability to induce CDC2 and CDK2, as well as stimulate DNA synthesis in response
      to TNF, progressively declined, with minimal to absent induction in senescent
      cells. This occurred despite the TNF-dependent induction of such proliferation
      independent genes as manganese superoxide dismutase and interleukin-6 in
      senescent and quiescent cells. Serum was similarly unable to induce CDC2 or CDK2
      expression in senescent cells. These results demonstrate that senescent cells are
      selectively deficient in TNF-mediated induction of CDC2 and CDK2, genes crucial
      to DNA synthesis and mitosis.

PMID- 8262135
TI  - Cytochemical localization of actin and myosin aggregates in interphase nuclei in
      situ.
AB  - Biochemical and ultrastructural studies on isolated nuclear compartments have
      previously shown actin and myosin to be constituents of interphase nuclei. In the
      present work, immunocytochemistry, in conjunction with confocal microscopy and
      ultrastructural immunogold techniques, shows that interphase nuclei of intact
      dorsal root ganglion neurons and of PC12 cells contain actin and myosin. Nuclear
      actin was observed to be distributed throughout the nucleoplasm occurring as
      distinct aggregates. Frequently, prominent actin aggregates were associated with
      the nucleolar periphery, often near nucleolar satellites. Ultrastructurally,
      actin was observed to be associated with linear, electron-dense structures,
      putatively identified as chromatin fibers, extending from nucleoli. Use of three
      antibodies against subclasses of alpha-actin isoforms revealed that nuclear actin
      is more closely related to alpha-sarcomeric actin than to alpha-smooth muscle
      actin. Those aggregates associated with the nucleolus were found to be in the
      polymerized F-actin form, in a small fraction of neurons, as assessed by FITC
      phalloidin. A myosin-like antigen was also observed to occur as intranuclear
      aggregates. Quantitative assays of the distribution of actin and myosin
      aggregates by nearest neighbour analysis indicated a distribution characterized
      as uniform and failed to reveal statistically significant associations between
      any set of aggregates. The evidence presented herein indicates that actin and
      myosin are constituent proteins of interphase nuclei in situ of both normal
      mammalian and transformed mammalian cells.

PMID- 8262136
TI  - Decorin, versican, and biglycan gene expression by keloid and normal dermal
      fibroblasts: differential regulation by basic fibroblast growth factor.
AB  - Basic fibroblast growth factor (bFGF) is a multipotential heparin-binding factor
      that belongs to the fibroblast growth factor (FGF) family. The FGFs demonstrate a
      wide spectrum of biologic activities in vivo and in vitro. In this study, we
      investigated the potential of bFGF to regulate the expression of various dermal
      extracellular matrix proteoglycans and type I collagen mRNAs in cultured human
      fibroblasts from keloid, which is a prototype of dermal fibrosis, and normal skin
      tissue. We report that bFGF upregulates the expression of the decorin gene in
      normal and keloid fibroblasts. In contrast, the expression of biglycan is
      downregulated by bFGF. The mRNA steady-state level of versican, a large
      proteoglycan, is not altered by bFGF. Type I collagen gene expression is
      downregulated substantially in keloid and normal fibroblasts by bFGF. The results
      suggest that the expression of the proteoglycan genes are uncoordinately
      regulated and that the gene expression of type I collagen and biglycan is
      coordinately downregulated. The results also demonstrate that keloid fibroblasts
      respond similarly as do normal fibroblasts to bFGF in the regulation of
      proteoglycan and collagen expression.

PMID- 8262137
TI  - Expression and purification of the DNA-binding domain of SRF: SRF-DB, a part of a
      DNA-binding protein which can act as a dominant negative mutant in vivo.
AB  - We have developed an approach which allows functional in vivo examination of DNA
      binding proteins through microinjection of polypeptides containing the DNA
      binding domain into living fibroblasts. The present analysis utilizes serum
      response factor (SRF), a transcription factor that binds to the serum response
      element. We have expressed in bacteria a 30-kDa portion of this protein (amino
      acids 113 to 265) containing the DNA-binding domain of SRF (SRF-DB) and purified
      it to homogeneity by a single DNA affinity chromatography step using the high
      affinity SRF-binding site (ACT.L). We have tested the efficiency of SRF-DB to
      prevent endogenous SRF function through analysis of c-fos expression and DNA
      synthesis stimulated by fetal calf serum, two events known to require SRF.
      Injection of purified SRF-DB into rat embryo fibroblasts inhibits c-fos induction
      by growth factors. Moreover, DNA synthesis, induced after serum addition, is also
      suppressed by SRF-DB injection. This implies that overproduction of SRF-DB makes
      the cell deficient in the function of wild-type SRF and that SRF-DB acts as a
      dominant negative mutant. These data show that, for the study of DNA-binding
      proteins, expressing and using portions of the protein that corresponds to the
      DNA-binding domain present a useful method for generating dominant negative
      mutants and illustrate the potential application of the DNA-binding region to
      facilitate the study of events at the DNA/protein level.

PMID- 8262138
TI  - Epidermal growth factor (EGF) promotes human keratinocyte locomotion on collagen
      by increasing the alpha 2 integrin subunit.
AB  - The migration of human keratinocytes across the would bed is an early and
      critical event in the reepithelialization of cutaneous wounds. Epidermal growth
      factor (EGF) has been shown to accelerate the healing of fresh, split-thickness
      cutaneous wounds when applied topically. The mechanism(s) by which this
      accelerated healing occurs remains unknown. Using an assay that directly
      evaluates human keratinocyte locomotion without confounding the possibility of
      cell proliferation, we examined the influence of EGF on human keratinocyte
      motility. Both recombinant epidermal growth factor (rEGF) and transforming growth
      factor-alpha (TGF-alpha) promoted human keratinocyte locomotion when the cells
      were apposed to connective tissue matrices of collagen or fibronectin, important
      components of the wound bed. Other growth factors studied did not enhance
      keratinocyte migration. Blocking the EGF/TGF-alpha receptor on the cell surface
      of keratinocytes with specific antibody inhibited the stimulation of keratinocyte
      locomotion by rEGF and TGF-alpha. Flow cytometry analysis of keratinocytes
      migrating on type I collagen in the presence of rEGF or TGF-alpha revealed
      increased expression of the alpha 2 integrin subunit on the keratinocyte surface.
      The alpha 2 beta 1 integrin mediates keratinocyte migration on collagens type I
      and IV, and inhibition of migration via antibody blockade of the alpha 2 beta 1
      integrin can be partially overcome by increasing the concentration of rEGF
      present in the medium. Our study demonstrates that the growth-independent
      stimulation of keratinocyte locomotion via regulation of integrin expression may
      be one mechanism by which EGF accelerates the reepithelialization of human
      cutaneous wounds.

PMID- 8262139
TI  - Regulation of basic fibroblast growth factor mRNA expression in rat C6 glioma
      cells.
AB  - Multiple basic fibroblast growth factor (bFGF) mRNAs are transcribed in rat brain
      at 6.0, 3.7, 2.5, 1.8, 1.6, 1.4, and 1.0 kb. These seven transcripts are also
      seen in Rat-1 fibroblasts and ras-transformed Rat-1 fibroblasts in culture.
      However, only a single bFGF transcript at 6.0 kb is detectable in the rat
      astrocytoma cell line, C6, and this mRNA is identical to that seen in a primary
      culture of cortical astrocytes. C6 glioma cells also transcribe message for FGF
      receptor 1 (FR1), suggesting possible autocrine growth by these cells. Growth
      factor activity in a C6 cell lysate was characterized by heparin affinity
      chromatography and Western blot analysis using an anti-bFGF antibody. Proteins of
      18, 21.5, and 22 kDa were detected in C6 cells, indicating that the 6.0-kb mRNA
      is translated into the three characteristic bFGF proteins. Rat-1 fibroblasts also
      synthesize bFGF proteins of identical molecular weight. The small transcripts
      detected in brain probably represent bFGF or FGF-related mRNAs in cell types
      other than glia, such as fibroblasts, endothelial cells, or neurons. In cultured
      C6 cells, bFGF protein levels are highest in confluent, quiescent cells, whereas
      mRNA levels are low. Addition of serum, phorbol ester, or cycloheximide to both
      C6 cells and fibroblasts induces the level bFGF mRNA transcripts 10-fold after 1
      4 h. This rapid induction after cell activation indicates that bFGF is an early
      response gene. Therefore, even though there are abundant intracellular stores of
      the factor, the transcriptional activation seen after mitogenic activation of
      cells implies that de novo bFGF mRNA synthesis is an important part of the
      mitogenic response.

PMID- 8262140
TI  - Investigation of the role of G1/S cell cycle mediators in cellular senescence.
AB  - Cellular senescence is a state of irreversible cell cycle arrest in which normal
      cells at the end of their lifespan fail to enter into DNA synthesis upon serum or
      growth factor stimulation. We examined whether proteins required for G1/S cell
      cycle progression were irreversibly down-regulated in senescent human
      fibroblasts. Both the 44- and 42-kDa forms of the MAP-kinase protein were
      expressed at similar levels in young and senescent cells. In contrast to young
      cells where both forms were phosphorylated on tyrosine in response to serum, the
      p42MAP-kinase was not tyrosine phosphorylated upon serum stimulation, whereas
      p44MAP-kinase was phosphorylated on tyrosine in serum-starved or serum-stimulated
      senescent cells. Examination of p53 protein in growing, quiescent, and senescent
      cells revealed no significant differences in levels between the different growth
      states. In contrast, cdk2 and cyclin A mRNAs were completely down-regulated in
      stimulated senescent fibroblasts, while the G1 cyclins, C, D1, and E mRNAs, were
      still expressed in stimulated senescent cells although at reduced levels compared
      to young cells. The expression of early G1 markers, but not late G1 markers,
      indicates that senescent cells may be blocked at a point in late G1. We
      investigated whether transfection of cyclin A, alone or in combination with cdc2,
      was sufficient for extension of lifespan or escape from senescence. Clones
      expressing the transfected human cyclin A or cdc2 genes senesced at a population
      doubling similar to controls, thereby showing that cyclin A or cdc2 expression
      alone was insufficient for escape from senescence.

PMID- 8262141
TI  - Evidence that the mechanism of prenatal germ cell death in the mouse is
      apoptosis.
AB  - Using fluorescence-activated cell sorting combined with fluorescence microscopy
      the mechanism of embryonic germ cell death in the mouse has been shown to be
      apoptosis. Primordial germ cells (PGCs) from embryos at specific developmental
      stages have been analyzed, and cells with apoptotic morphology have been isolated
      by cell sorting. In the female, apoptotic oogonia at Day 13 and apoptotic oocytes
      at Days 15 and 17 were found. In the male, apoptotic cells were seen on Day 13
      through Day 17. Apoptotic germ cells were not detected at Day 12 (combined male
      and female PGCs). Examination of sorted cells by fluorescence microscopy and by
      light microscopic analysis after alkaline phosphatase staining confirmed that the
      cells are apoptotic germ cells. Electron microscopy further confirmed that cells
      showing the morphological characteristics of apoptosis are present.

PMID- 8262142
TI  - Establishment of permanent brown adipocyte cell lines achieved by transfection
      with SV40 large T antigen and ras genes.
AB  - We established multiple clonal cell lines by transfection of primary rat fetal
      brown adipocytes (BAT) with constitutive or inducible gene constructs of SV40
      large T antigen (SVLTag) alone or in combination with transforming or normal ras
      genes. While primary BAT cell cultures stop growing and expressing uncoupling
      protein (UCP) after several passages in culture, our transfected cell lines could
      be propagated indefinitely and kept properties specific of BAT cells.
      Interestingly, cells transfected with ras genes alone did not survive as
      permanent cell lines. In contrast, cells transfected with SVLTag alone or in
      combination with various ras genes could readily be established as continuous
      cell lines. BAT cells transfected with SVLTag alone showed fibroblastic, flat
      morphology and clear contact inhibition of growth. In contrast, cells
      cotransfected with SVLTag and ras genes were more fusiform and possessed
      increased proliferative capacity. Thus, cells cotransfected with normal ras
      reached higher cell density at confluency, while cells cotransfected with
      transforming ras were clearly refractile, lost contact inhibition of growth, and
      presented a transformed phenotype. These results are consistent with the notion
      that ras genes are inefficient at overcoming senescence of primary BAT cells and
      can only confer improved proliferative ability to cells that have already been
      immortalized by a cooperating SVLTag gene. RNA analysis showed that most
      transfected cell lines expressed UCP along with the exogenously transfected
      genes. This demonstrated that genuine BAT cells, and not other possible
      contaminating cell lineages, gave rise to our selected cell lines. The variety of
      cell lines generated may correspond to various stages of progression through BAT
      development and therefore be useful to characterize signaling pathways and
      metabolic regulation of this particular tissue.

PMID- 8262143
TI  - DNA topoisomerase II is not detectable on lampbrush chromosomes but enriched in
      the amplified nucleoli of Xenopus oocytes.
AB  - In somatic cells DNA topoisomerase II (topo II) is thought to be involved in the
      domain organization of the genome by anchoring the basis of chromatin loops to a
      chromosomal scaffold. Lampbrush chromosomes of amphibian oocytes directly display
      this radial loop organization in cytological preparations. In order to find out
      whether topo II may play a role in the organization of these meiotic chromosomes,
      we performed immunofluorescence studies using antibodies against Xenopus topo II.
      Our results indicate that topo II is apparently absent from lampbrush chromosomes
      and is hence unlikely to act as a "fastener" of the numerous lateral chromosomal
      loops. Topo II was, however, enriched in the amplified nucleoli of Xenopus
      oocytes.

PMID- 8262144
TI  - A temperature-sensitive cell cycle arrest mutation affecting H1 phosphorylation
      and nuclear localization of a small heat shock protein in Tetrahymena
      thermophila.
AB  - This report describes a temperature-sensitive Tetrahymena thermophila cell cycle
      arrest mutant that is also deficient in its heat shock response. Mutants
      incubated at 41 degrees C undergo rapid dephosphorylation of macronuclear histone
      H1, in contrast to wild-type cells which hyperphosphorylate H1 under the same
      conditions. Dephosphorylation is specific to H1 and is associated with a
      threefold decrease in the level of H1 kinase activity in macronuclei isolated
      from heat-shocked mutants. A small nuclear heat shock protein, sp29c, is
      synthesized and phosphorylated normally in the mutant cells but fails to
      accumulate in macronuclei. Nuclear transport of other heat shock proteins is
      unaffected. Mutant cells die slowly at 41 degrees C, a temperature at which wild
      type cells resume normal growth after a brief lag. Wild-type cells acquire
      thermotolerance (competence to survive a 3-h heat shock at 43 degrees C) after a
      1-h treatment at 41 degrees C, but mutant cells cannot become thermotolerant and
      die after the same treatment. The mutation is named chp 1 (cell cycle, heat
      shock, and phosphorylation defect).

PMID- 8262145
TI  - Polarized secretion of human corticosteroid binding globulin by MDCK and BeWo
      cells.
AB  - Polarized epithelial cells are able to faithfully direct certain secretory
      protein components to either their apical or basolateral environments. The
      mechanism by which these cells accomplish this is still not entirely understood.
      It is hypothesized that a membrane-associated "sorting receptor" recognizes an
      intrinsic signal contained within the sorted protein. This interaction directs
      the secretory protein into the appropriate domain-specific vesicle for transport
      to either the apical or basolateral face. The nature of this sorting signal and
      the recognition receptor have not been established. In an effort to understand
      this phenomenon, a study was undertaken to ascertain whether human corticosteroid
      binding globulin (hCBG) contains intrinsic signals capable of directing its
      secretion to a particular side of polarized epithelial cells. The results of
      these studies have revealed that hCBG is selectively secreted into the apical
      environment by both MDCK and BeWo cells. Furthermore, this polarized secretion is
      unaffected by either (1) agents that inhibit N-linked oligosaccharide processing
      or (2) lysomotrophic drugs, which alter the intravesicular pH. It is concluded
      that hCBG possesses an intrinsic signal for apical secretion, which can be
      recognized by two polarized cell types of differing origins. This signal does not
      appear to be present in the N-linked oligosaccharide moieties of hCBG nor is it
      affected by an elevation of the intravascular pH within the trans-Golgi network.
      The use of hCBG-transfected MDCK and BeWo cells constitute a useful model system
      for the investigation of the signals involved in the sorting of secreted
      proteins.

PMID- 8262146
TI  - Identification of a cDNA coding for a Ca(2+)-binding phosphoprotein (p90),
      calnexin, on melanosomes in normal and malignant human melanocytes.
AB  - In order to have a proper biosynthesis and secretion of the melanin-pigment
      granules (melanosomes) the melanocyte may require a melanosome-associated
      molecule that provides a signal for assembly and organization of melanogenic
      enzymes and proteins within the compartment of melanosomes. This study reports
      the presence of a Ca(2+)-binding phosphoprotein, p90, which can be engaged in
      such melanogenic function, located on the melanosomal membrane of human
      melanocytes. A human melanoma cDNA expression library in lambda Zap II was
      screened with a rabbit polyclonal antibody raised against human melanosomes
      isolated from cultured human melanoma cells, SK MEL 23. A cDNA encoding a
      melanosomal protein, M(r) 90 kDa, was identified through this immunoscreening. A
      partial sequencing of nucleotides (822 bp from the N-terminal domain) of this
      clone (3.8 kb) and predicted amino acids showed more than 90% homology with dog
      calnexin, a previously reported endoplasmic reticulum (ER) transmembrane protein.
      A fusion protein of this p90 with beta-galactosidase expressed in Escherichia
      coli revealed both the immuno-cross-reactivity with anti-dog calnexin and anti
      human melanosome antibodies and the Ca(2+)-binding property. Upon
      immunohistochemistry, the anti-dog calnexin antibody revealed the positive
      immunoreactivities with both normal and malignant human melanocytes, showing a
      much higher expression of antigenic epitope than nonmelanocytic human cells. The
      laser scanning confocal immunofluorescence, using an antibody against a human
      melanosome-specific antigen (HMSA-5), and immunoelectron microscopy, using
      immunogold, confirmed the major localization of anti-dog calnexin antibody
      epitope on the melanosomes and ER.

PMID- 8262147
TI  - Predesquamin inhibits desquamation.
AB  - Predesquamin is a Con A binding glycoprotein from human epidermis, with a
      molecular weight of 650 kDa. Its isolation and characterization are detailed, as
      well as the preparation of a polyclonal antibody to it. The antibody labels
      primarily the lower stratum corneum in fluorescent and ultrastructural
      immunolocalization, both in normal skin and plantar callus. A desquamation model
      system, in which plantar callus is incubated with the chelating agent
      ethylenediaminetetraacetic acid (EDTA) is refined by substituting for EDTA the
      Ca(2+)-specific ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid.
      Moreover, the shedding activity can be suppressed by raising the Ca2+
      concentration. Within this model, it is demonstrated that predesquamin at
      nanomolar concentrations inhibits squame shedding in a dose-dependent manner. We
      conclude that predesquamin plays an important role in blocking premature
      desquamation of the lower stratum corneum.

PMID- 8262148
TI  - Influence of the content in transcription factors on the phenotype of mouse
      hepatocyte-like cell lines (mhAT).
AB  - We have described new well-differentiated mouse hepatocyte-like cell lines (mhAT)
      derived from transgenic mice expressing simian virus 40 large T antigen under the
      control of antithrombin III gene promoter (Exp. Cell Res. (1992) 200, 175-185).
      In an attempt to understand the phenotypic variations of the different cell
      lines, we analyzed their content in liver-specific transcription factors at the
      level of both the proteins, by gel shift analysis, and the mRNA, by quantitative
      reverse-transcription PCR. Moreover, the transactivating ability of endogenous
      HNF1 alpha and C/EBP alpha was also evaluated by measuring the activity of
      transfected synthetic promoters consisting of DNA element homopolymers upstream
      of a TATA box. High levels of HNF1, HNF3, and HNF4 transcription factors were
      maintained in mhAT cells. In contrast, C/EBP alpha was much more variable between
      the different cell lines and was less abundant than it was in vivo, in the liver.
      We investigated the influence of HNF1 alpha and C/EBP alpha on the activity of
      transfected liver-specific promoters. HNF1 alpha was not limiting for the
      activity of transfected liver-type pyruvate kinase and albumin promoters. In
      contrast, the activity of the albumin promoter in the different lines was clearly
      dependent on the C/EBP alpha content, which seems, therefore, to be an essential
      factor modulating the expression of this gene in HNF1 alpha-containing cells.
      This work shows that the correlations between promoter activities and transacting
      factor contents in a panel of well-differentiated cultured cells can be used to
      determine the respective role of transcription factors on the strength of some
      promoters.

PMID- 8262149
TI  - Heparin modulates the receptor-binding and mitogenic activity of hepatocyte
      growth factor on hepatocytes.
AB  - Hepatocyte growth factor (HGF) is a mitogen for hepatocytes, having high affinity
      for heparin. In this study, we examined the function of cell surface heparin-like
      molecules in HGF/receptor interaction and HGF-induced mitogenic activity using
      hepatocytes. Binding studies using 125I-HGF showed that more than 85% of bound
      HGF was released from the cell surface by washing with heparin. This procedure
      also released HGF from the c-Met protein, which is a component of the high
      affinity receptor. In addition, heparitinase digestion of hepatocytes reduced the
      HGF bound to c-Met protein. Furthermore, excess heparin added during the binding
      of 125I-HGF to hepatocytes, significantly diminished HGF bound to c-Met protein.
      Moreover, when DNA synthesis of hepatocytes was repressed and retarded by excess
      HGF, exogenous heparin restored it. These results suggest that HGF is bound to c
      Met protein and that its mitogenic activity is regulated by heparin-like
      molecules on hepatocytes.

PMID- 8262150
TI  - Expression of the cytoskeletal-associated protein filamin in adult rat organs.
AB  - Filamin is a well-characterized actin-associated protein first isolated from
      chicken smooth muscle. Subsequently, this polypeptide and its nonmuscle homolog
      actin-binding protein have been shown to be expressed in avian muscle tissue,
      mammalian smooth muscle, mammalian macrophages and other blood cell types, as
      well as several cultured cell lines. In this report, the occurrence of this
      polypeptide in adult mammalian organs has been investigated. Immunoblot analysis
      using three anti-filamin monoclonal antibodies showed that this protein was
      largely detected in adult rat organs that possess a substantial smooth muscle
      component. Furthermore, the limited expression of filamin in smooth muscle tissue
      was corroborated by immunohistochemical analysis. In contrast to avian systems,
      filamin was never found in detectable quantities in either mammalian cardiac or
      skeletal muscle. Quantitative immunoblot analysis demonstrated that filamin
      amounts roughly correlated with the abundance of the smooth muscle component of a
      given organ, comprising as much as 16.5% of the total SDS-extractable protein in
      bovine aorta. Work in avian systems and cells in culture has suggested that
      filamin is a rather ubiquitous cytoskeletal element. By contrast, this work
      demonstrates that filamin is highly restricted in its expression in mammalian
      organ systems, in situ.

PMID- 8262151
TI  - Brefeldin A inhibits muscle-specific gene expression during differentiation in
      C2C12 myoblasts.
AB  - In analyzing regulatory mechanisms underlying differentiation-dependent
      expression of muscle proteins, we have found that mouse C2C12 myoblast cells
      treated with Brefeldin A (BFA), which specifically blocks the intracellular
      transport of protein from endoplasmic reticulum (ER) to the Golgi apparatus,
      failed to differentiate. BFA reversibly inhibited myotube formation at a
      threshold concentration of 1.0 micrograms/ml. The same concentration of BFA
      completely blocked accumulation of secretory proteins, e.g., fibronectin into the
      culture medium, probably due to retention in ER. Interestingly, the induction of
      muscle creatine phosphokinase (MCK) activity was sensitive to BFA, although a
      constitutive expression of lactate dehydrogenase, one of the cytosolic
      housekeeping enzymes, was resistant to BFA. In the kinetic analysis of MCK
      induction, translation of existing MCK mRNA was not inhibited by BFA since MCK
      activity became resistant to BFA once levels of MCK transcript accumulated. The
      differentiation-dependent accumulation of MCK transcript was also suppressed by
      BFA treatment to approximately 30% of control, although neither general
      transcriptional activity in vivo nor stability of existing mRNAs was affected
      even in the presence of BFA. Moreover, induction of muscle regulatory genes,
      MyoD1 and myogenin, which are upstream of the MCK gene, were inhibited at their
      transcription level by BFA. Such an effect on muscle regulatory gene
      transcription by BFA suggests that transport of some factor(s) to the cell
      surface may be a prerequisite for the muscle-specific gene expression upon
      differentiation of C2C12 myoblasts.

PMID- 8262152
TI  - Cilia, ciliary concanavalin A-binding proteins, and mating recognition in
      Tetrahymena thermophila.

PMID- 8262153
TI  - Localization and characterization of the 86- and 84-kDa heat shock proteins in
      Hepa 1c1c7 cells.
AB  - The 90-kDa heat shock protein (hsp90) is present in cells at high levels in the
      cytoplasm and is composed of two separate gene products, hsp86 and hsp84. Rabbit
      polyclonal antibodies to the murine N-terminal sequences of the 86- and 84-kDa
      heat shock proteins were isolated from serum by peptide affinity chromatography.
      Antibodies against each form of hsp90 are capable of immunoprecipitating hsp90.
      Each antibody preparation is specific against either hsp86 or hsp84 when tested
      on a protein blot of Hepa 1c1c7 cytosol. The over-all ratio of hsp84/hsp86 in
      Hepa 1 cytosol was estimated to be 2 to 1. Each antibody preparation was used to
      immunoprecipitate hsp84 or hsp86 from Hepa 1 cytosol to test whether hsp86/84
      exists as a homo- and/or heterodimer. After electrophoresis, silver staining
      revealed that anti-hsp86 antibodies immunoprecipitated both hsp86 and hsp84. This
      result would suggest that hsp86 forms heterodimers with hsp84. In contrast, the
      anti-hsp84 antibodies immunoprecipitated almost entirely hsp84, suggesting that
      hsp84 exists largely as homodimers. Both anti-hsp86 and hsp84 antibodies were
      able to immunoprecipitate the 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dixoin
      labeled Ah receptor from Hepa 1 cytosol, indicating that these antibodies are
      able to bind to hsp90 when it is complexed with other proteins. Both antibody
      preparations recognize hsp90 in mouse, rat, and human cell lines.
      Immunofluorescence and confocal microscopy were performed using both antibody
      preparations, and the results indicated that both hsp86 and hsp84 were located in
      the cytoplasm and nucleus of Hepa 1 cells. Hsp86 was found to localize unevenly
      in the cytoplasm, while hsp84 was found evenly dispersed throughout the
      cytoplasm. Hsp86 also appeared to be localized to a greater degree than hsp84 in
      the vicinity of the nuclear envelope.

PMID- 8262154
TI  - Effect of ATP on the release of hsp 70 and hsp 40 from the nucleus in heat
      shocked HeLa cells.
AB  - We have recently found a novel 40-kDa heat-shock protein (hsp 40) in mammalian
      and avian cells and reported that the N-terminal amino acid sequence of mammalian
      hsp 40 has homology with the bacterial DnaJ heat-shock protein. Also, hsp 40 has
      been shown to be translocated from the cytoplasm into the nuclei/nucleoli by heat
      shock and colocalized with hsc 70 (p73) in the nucleoli of exactly the same
      cells. We here investigated the effect of ATP on the release of hsp 70 (both
      constitutive p73 and inducible p72) and hsp 40 from the nuclei/nucleoli of heat
      shocked HeLa cells which were permeabilized with Nonidet-P40 using
      immunofluorescence and immunoblotting. Hsp 70 in the nucleoli was released by the
      addition of ATP but not by ADP, GTP, nonhydrolyzable ATP, nor high salt buffer.
      In contrast, hsp 40 was not released from the nucleoli with any of these
      treatments or any combination of these treatments. Thus, hsp 40 might dissociate
      spontaneously from the nucleoli after hsp 70 has been released in an ATP
      dependent manner. Using cell fractionation methods, we showed that while the
      majority of hsp 40 is localized in the cytoplasm, a small portion of it is
      located in the microsome fraction in non-heat-shocked control cells and in cells
      which recovered from heat shock.

PMID- 8262155
TI  - 1,25-Dihydroxyvitamin D3 protects HL60 cells against apoptosis but down-regulates
      the expression of the bcl-2 gene.
AB  - Exposure of myeloid leukemia cells to analogs of vitamin D results in monocytic
      like maturation of several variants of these cells. We report here that brief
      treatment of HL60 cells with differentiation-inducing concentrations of 1,25
      dihydroxyvitamin D3 (1,25(OH)2D3) makes these cells resistant to cell death by
      apoptosis. Resistance was studied by using the calcium inophore A23187 and the
      cancer chemotherapeutic drugs 1-beta-D-arabinocytosine and etoposide. Apoptosis
      was detected by the characteristic morphology under light microscopic
      examination, presence of DNA "ladders" on agarose gel electrophoresis, DNA
      fragmentation by filter elution assay, and the "apoptotic index" obtained by
      comparison of damage to mitochondrial and nuclear genes on Southern blots. The
      protective effect of 1,25(OH)2D3 treatment was apparent before the phenotypic
      evidence of differentiation and before altered traverse of the cell cycle could
      be detected. Northern and Western blot analysis showed that the expression of bcl
      2 proto-oncogene was rapidly reduced by 1,25(OH)2D3, which excludes the
      involvement of this gene in the protective effect. The rapidity of the protective
      effect of 1,25(OH)2D3 is consistent with the hypothesis that the activation of
      the monocytic differentiation program is sufficient to interfere with programs
      that lead to cell death by apoptosis.

PMID- 8262156
TI  - An evaluation of the effects of cytokines on intracellular oxidative production
      in normal neutrophils by flow cytometry.
AB  - To evaluate the effects of inflammatory cytokines on oxidative production in
      normal neutrophils, seven kinds of cytokines such as granulocyte-macrophage
      colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G
      CSF), interleukin-2 (IL-2), IL-6, IL-1 alpha, IL-1 beta, and interferon-beta (IFN
      beta) were tested. The intracellular hydrogen peroxide (H2O2) in individual cells
      was determined by flow cytometry. According to the levels of intracellular H2O2
      enhanced by cytokines, these seven cytokines were classified into three types:
      (1) prominently effective--GM-CSF; (2) moderately effective--G-CSF, IL-6, and IL
      2; (3) weakly or ineffective--IFN-beta, IL-1 alpha, and IL-1 beta. Changes in
      cell size and cell surface structure after stimulation of those seven cytokines
      were simultaneously measured by flow cytometry. The most prominently effective
      cytokine, GM-CSF, initially caused enlargement of cell size and irregularity of
      the cell surface and subsequently increased H2O2 production by neutrophils. In
      contrast, the weakly or ineffective cytokines, like IL-1 beta, had no effects on
      cell size or cell surface. Our study indicates that some kinds of cytokines
      enhance oxidative production and cause morphological changes in neutrophils.

PMID- 8262157
TI  - Establishment of gastric surface mucous cell lines from transgenic mice harboring
      temperature-sensitive simian virus 40 large T-antigen gene.
AB  - We succeeded in establishing two gastric surface mucous cell lines (designated as
      GSM06 and GSM10), which produce periodic acid-Schiff (PAS)- and concanavalin A
      (Con A)-positive glycoproteins, from a primary culture of gastric fundic mucosal
      cells of adult transgenic mice harboring a temperature-sensitive simian virus 40
      large T-antigen gene. At the permissive temperature (33 degrees C), GSM06 and
      GSM10 cells grew until confluent monolayers were formed and have now been in
      culture for more than 9 months with regular passaging. Con A-horseradish
      peroxidase- and PAS-positive staining indicated that these cells retain the
      characteristics of gastric surface mucous cells. GSM06 cells showed temperature
      sensitive growth in culture and expressed SV40 large T-antigen at the permissive
      temperature but not at a nonpermissive temperature (39 degrees C). In contrast,
      GSM10 cells showed temperature-insensitive growth and expressed T-antigen at both
      permissive and nonpermissive temperatures. To our knowledge, this is the first
      report of the establishment of gastric surface mucous cell lines from animals.
      These immortalized cell lines with normal characteristics may serve as good
      experimental models for the basic and applied biology of gastric surface mucous
      cells.

PMID- 8262158
TI  - Tropomodulin is highly concentrated at the postsynaptic domain of human and rat
      neuromuscular junctions.
AB  - Tropomodulin is expressed in skeletal muscle and recent studies suggest that
      tropomodulin is associated with synaptic membranes. Therefore, we have examined
      neuromuscular junctions by immunofluorescence analysis for tropomodulin
      localization. Anti-tropomodulin antibodies generated against either the whole
      protein or a 15-amino acid peptide fragment label human neuromuscular junctions
      as demonstrated by colocalization with alpha-bungarotoxin label. Tropomodulin
      labeling also colocalizes with desmin and beta-amyloid proteins which are
      concentrated in the postsynaptic region. Comparable results are found with
      immunostaining of neuromuscular junctions in rat diaphragm muscle. These
      immunofluorescence results suggest that tropomodulin is an integral component of
      the cytoskeletal lattice associated with the postsynaptic region of neuromuscular
      junctions.

PMID- 8262159
TI  - Correction of steroid sulfatase deficiency by gene transfer into basal cells of
      tissue-cultured epidermis from patients with recessive X-linked ichthyosis.
AB  - To develop an experimental model for somatic gene therapy we have tried to
      correct the steroid sulfatase (STS) deficiency in tissue-cultured primary
      epidermal keratinocytes from patients suffering from recessive X-linked
      ichthyosis. An efficient Epstein-Barr virus-based vector was constructed, in
      which full-length steroid sulfatase cDNA is located between an SV40 early
      promotor and processing signals. After STS gene transfer into cultured basal
      cells from ichthyotic skin, the cells produce large amounts of enzymatically
      active steroid sulfatase protein. The subpopulation of transfected cells can be
      made to produce approximately 100 times more STS activity than normal
      keratinocytes. Keratinocytes from patients suffering from recessive X-linked
      ichthyosis display an abnormal phenotype when developing a multilayered tissue in
      culture: Initially an extensive burst of keratinization is observed, followed by
      rapid, premature shedding and degradation of most suprabasal cell layers, leaving
      a culture with hyperproliferative relatively immature keratinocytes. Transfection
      of these immature ichthyotic cells with the functional STS construct led to an
      increase in the amount of retained cell material in the culture medium,
      indicating an increased cell maturation. It is possible to genetically label
      individual transfected epidermal cells with a reporter gene. Cotransfection
      experiments with STS and reporter gene vectors show that the cohort of
      transfected cells had a tendency to develop less rapidly since they became
      overrepresented in the smaller size classes at the same time the total population
      was somewhat shifted toward higher cell sizes. We interpret these results as an
      indication that restoration of the enzymatic activity induces a more normal
      maturation of the transfected keratinocytes.

PMID- 8262160
TI  - Protein kinase C is not involved in the homologous desensitization of bombesin
      responses in small cell lung cancer cells.
AB  - Homologous desensitization of responses to bombesin in small cell lung cancer
      cells can be mimicked by protein kinase C-activating phorbol esters. We show that
      phorbol ester-induced desensitization can be blocked by prior treatment with the
      protein kinase C inhibitor staurosporine or prolonged pretreatment with phorbol
      esters. However, under these conditions, homologous desensitization to bombesin
      persists. These data indicate that phorbol ester-induced desensitization is
      distinguishable from bombesin-induced homologous desensitization. Protein kinase
      C is not a dominant component in the homologous desensitization to bombesin in
      small cell lung cancer cells.

PMID- 8262161
TI  - Quantitative investigations of apoptosis of murine mononuclear phagocytes during
      mild hyperthermia.
AB  - DNA fragmentation in murine monocytes and freshly harvested resident peritoneal
      macrophages (RPM) was assessed. Similar proportions of fragmented DNA were
      present in both cell types indicating that apoptosis is a significant occurrence
      in these cells and may provide a mechanism for controlling the numbers of
      mononuclear phagocytes in the tissues that house them. Culturing both of these
      cell types at 41 degrees C for 5 hr revealed a significant increase in the
      proportion of fragmented DNA only in cultures containing RPM. These latter
      preparations when cytophotometrically assessed also displayed reduced Feulgen DNA
      and cytoplasmic naphthol yellow S staining, again confirming the presence of
      apoptosis. It is suggested that the induction of apoptosis by mild hyperthermia
      may therefore be due to the relative absence of a temperature-sensitive inhibitor
      of apoptosis in a significant proportion of resident peritoneal macrophages.
      Lastly, electron microscope assessment indicated that the apoptotic macrophages
      were engulfed by their nonaffected neighbors. Programmed cell death in macrophage
      populations followed by phagocytosis of the apoptotic cells may therefore be a
      mechanism for controlling macrophage numbers in mammalian organisms.

PMID- 8262162
TI  - A new method for the investigation of endocrine-regulated autophagy and protein
      degradation in rat liver.
AB  - The effect of the antilipolytic agent 3,5-dimethylpyrazole (DMP) on liver
      autophagy and protein degradation was studied on male young adult rats (200 g
      body wt) of the Sprague-Dawley strain by electron microscopy and short-term
      single-pass liver perfusion and HPLC amino acid assay in the perfusate. Treatment
      with DMP (12 mg/kg body wt) enlarged the lysosomal-autophagic compartment in
      liver cells in 30 min and increased significantly the concentrations of valine
      and total amino acid in blood plasma (taken at sacrifice) and valine
      concentration in the liver perfusate in 60 min. These effects of DMP stimulating
      liver were secondary to the metabolic and endocrine effects of the drug (which
      caused a decrease in FFA, glucose, and insulin and an increase in glucagon and
      corticosterone plasma levels with a shorter latency, about 15 min). The effects
      of DMP were compared to those of other treatments inducing liver autophagy and
      protein degradation in vivo. Alterations after DMP or glucagon injections were
      similar, but they were larger and lasted for a longer time with DMP
      administration. Treatment with vinblastine or chloroquine enlarged the lysosomal
      autophagic compartment without increasing protein breakdown.

PMID- 8262163
TI  - Aged mice are resistant to the hepatotoxic effects of endotoxin and
      galactosamine.
AB  - The ability of concurrent intraperitoneal injections of endotoxin (0.1
      micrograms/kg) and galactosamine (700 mg/kg) to produce liver damage was
      determined in fasted C57Bl/6 mice of different ages: 2 months (young), 6 months
      (mature), and 24 months (aged). Liver damage was assessed after 6 hr by
      measurement of plasma alanine aminotransferase activity (ALAT, mumole/liter/min)
      and by histological examination for mature and aged mice. Control mice, those
      treated with saline, galactosamine, endotoxin, or hydrazine alone, had ALAT
      activities which ranged from 13 to 72 (n = 21). Plasma ALAT activities were
      increased to hepatotoxic values in some, but not all, mice injected with both
      endotoxin and galactosamine. For young mice, 7/11 had increased plasma ALAT
      activities; for mature mice, 5/8 had increased plasma ALAT activities and
      substantial centrilobular necrosis, whereas for aged mice, 0/7 had increased ALAT
      activities and none had centrilobular necrosis. Basophilic staining of the
      cytoplasm was increased by administration of endotoxin and/or galactosamine in
      both mature and aged mice whether or not necrosis was present. A 5-hr
      pretreatment with hydrazine sulfate (80 mg/kg) substantially decreased the ALAT
      release caused by endotoxin and galactosamine in mature mice. Hydrazine
      pretreatment prevented centrilobular necrosis in mature mice and decreased
      basophilic cytoplasmic staining in aged mice. The results demonstrate that aged
      mice are resistant to the hepatotoxic effects of endotoxin and galactosamine
      which were observed in both young mice and mature mice. Also, hydrazine sulfate
      pretreatment will protect against the hepatotoxic effects as well as the lethal
      actions of endotoxin and galactosamine.

PMID- 8262164
TI  - acLDL binding and endocytosis by macrophages and macrophage foam cells in situ.
AB  - The direct binding and internalization of acLDL by monocyte-derived macrophages
      associated with atherosclerotic lesions in the White Carneau pigeon were
      observed. Using an organ culture labeling protocol, pigeon thoracic aortae
      containing atherosclerotic lesions were incubated with colloidal gold-acLDL
      conjugates. When analyzed by electron microscopy acLDL-gold was bound and
      internalized by monocyte-derived macrophages residing on the lumenal surface of
      the endothelium. Macrophage foam cells located within the intima and projecting
      from the lesion into the arterial lumen also bound and internalized acLDL. In
      contrast, acLDL was not observed in spherical (nonactivated) monocytes adherent
      to the lesion surface. Colabeling experiments with acLDL in combination with beta
      VLDL resulted in the preferential (> 90%) binding and internalization of acLDL by
      macrophages and macrophage foam cells. The results of this study indicated that
      macrophages located on the endothelial surface were able to bind and internalize
      lipoprotein, although this binding and internalization was enhanced in foam cells
      spanning the endothelium to the subendothelial intima. Acetyl-LDL binding and
      internalization was effectively inhibited through competition studies using an
      excess of unconjugated acLDL. Through the direct observation of lipoprotein
      binding by macrophages and foam cells, we have demonstrated the expression of a
      functional receptor for modified lipoprotein on monocyte-derived macrophages
      during different stages of association with foam cell lesions.

PMID- 8262165
TI  - Effect of hydroxymethylglutaryl-CoA reductase inhibitors on the functional
      properties of erythrocyte membranes.
AB  - We studied 56 patients affected by primary hypercholesterolemia treated with
      placebo for 1 month and with simvastatin (20 mg/day) or pravastatin (20 mg/day)
      for 6 months during a double-blind clinical trial. At 1-month intervals we
      determined the following parameters in the serum: total and HDL cholesterol,
      triglycerides, and apolipoprotein A-1 and B. At the same time intervals we also
      determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase
      activity, and the fluidity of erythrocyte membranes. Our results demonstrated the
      following modifications in the erythrocyte membranes during simvastatin and
      pravastatin treatments: (1) an initial increase in cholesterol concentration and
      in cholesterol/phospholipid molar ratio, with a significant decrease only after 4
      months; (2) a similar behavior of membrane fluidity, with an initial decrease and
      an elevation after 4 months; (3) an increase in the Na+/K+ ATPase activity only
      after 4 months. We hypothesize that simvastatin and pravastatin not only inhibit
      the hepatic synthesis of cholesterol, but also modify the cholesterol exchange
      between plasma and the erythrocyte membrane.

PMID- 8262166
TI  - Healing and muscular restoration of the ureteral wall following balloon-induced
      rupture: an experimental animal model with light microscopic and ultrastructural
      observations.
AB  - Ureteral regrowth following balloon-induced rupture was studied using an animal
      model, with emphasis on the pattern and cellular events of self-reconstitution in
      the late phase of healing. At 4 weeks, the ureteral healing/remodeled region
      included a wedge-shaped muscular component which pointed toward a fibrous central
      zone, was continuous with the adjacent muscularis propria, and abutted on a thin
      lining epithelium. Progressive enlargement, aggregation, and bundle formation of
      myogenic cells was observed along the centrifugal axis. At 7 weeks, there was
      near-total muscular continuity, a rudimentary lamina propria, and partial
      periluminal folding. Muscular restoration was unaffected by the use of a stent,
      but epithelial metaplastic changes were observed. The intermediate zone showed
      admixed fibroblasts, immature and mature myogenic cells, and myofibroblasts.
      Frequent plasmalemmal appositions and junctions were observed between different
      cell types, whereas myofibroblasts were not associated with cell-to-stroma
      attachments. Myofibroblasts might play more than a contractile role in this phase
      of ureteral healing, possibly having an induction role and/or representing a
      transient form in myogenic differentiation.

PMID- 8262167
TI  - Mechanisms of tolerance in the copper-loaded rat liver.
AB  - The aim of this study was to contribute to the understanding of the pathogenesis
      of copper-induced damage and subsequent recovery and tolerance to copper in the
      copper-loaded rat liver. Male Wistar rats were allocated randomly into groups of
      four, fed a pelleted diet containing 1500 mg/g copper, and killed at 1, 5, 6, 10,
      and 15 weeks. Two additional groups were treated as follows: (a) 5 weeks copper
      loading followed by 5 weeks with normal rodent diet (group 5-0), (b) 5 weeks
      copper loading followed by 5 weeks normal diet and 5 weeks of copper reloading
      (group 5-0-5). Control rats were fed a normal rodent diet that contained 18 mg/kg
      of copper. Tissues were collected for histology, histochemistry,
      immunocytochemistry, and copper analysis by atomic absorption spectrophotometry
      and X-ray microanalysis. In the rats continuously fed the high copper diet,
      copper concentration rose to 444 +/- 32 micrograms/g of liver (wet weight) by
      Week 1 and to 726 +/- 170 micrograms/g at Week 5, decreasing to 417 +/- 9
      micrograms/g at Week 15. X-ray microanalysis and dot mapping microanalysis
      demonstrated copper within the nucleus, nucleolus, and lysosomes of these
      continuously loaded rats. Recovery with unloading of liver copper was
      demonstrated by both qualitative and quantitative methods in group 5-0 (41.32 +/-
      19 micrograms/g). Recovery and tolerance were associated with a reduction in
      nucleolar copper. Copper tolerance was demonstrated in group 5-0-5 and in
      continuously copper-loaded rats by Weeks 10 and 15. Copper tolerance was
      reflected by a change in intracellular levels and distribution of copper and an
      efficient copper unloading mechanism.

PMID- 8262168
TI  - The Medicaid eligibility expansions for pregnant women: evaluating the strength
      of state implementation efforts.
AB  - Surveys of state Medicaid agencies and maternal and child health programs were
      conducted in late 1991 and in 1992 to evaluate the extent to which states carried
      out a series of federal policy changes intended to improve low-income women's
      access to prenatal care. The results show a great deal of variability in the
      aggressiveness with which states implemented these Medicaid eligibility
      expansions. Overall, North Carolina, Maryland, Massachusetts, New York and
      Arkansas moved most aggressively to carry out the expansions; Kansas, Nebraska,
      South Dakota, North Dakota and Wyoming were ranked least aggressive. States with
      relatively high levels of poor birth outcomes or low-birth-weight deliveries
      prior to the Medicaid expansions were generally more likely than other states to
      have undertaken reforms intended to increase the number of women eligible for
      assistance and ease their enrollment. In addition, expansion efforts were greater
      in states where the federal government paid more of the cost of caring for
      Medicaid recipients.

PMID- 8262169
TI  - Demographic characteristics of heterosexuals with multiple partners: the National
      AIDS Behavioral Surveys.
AB  - In a study of risk behavior among heterosexuals, 9% of a national sample and 12%
      of a sample drawn from high-risk cities report having two or more sexual partners
      in the year before the survey. In both samples, sex with multiple partners is
      most common among men, younger people and the unmarried. Multivariate analyses
      show that racial and ethnic differences in the proportion of respondents with
      multiple partners vary by marital status. The results indicate that many
      heterosexuals are failing to protect themselves against sexually transmitted
      diseases: Among respondents with multiple partners, only 18% of men and 22% of
      women always use condoms with their primary partner, and 28% of men and 32% of
      women always use them with secondary partners. These proportions do not increase
      significantly with the number of partners; in general, almost half of men and
      women with multiple partners never use condoms.

PMID- 8262170
TI  - Contraceptive and sexual practices among single women with an unplanned
      pregnancy: partner influences.
AB  - Data from an urban obstetrics clinic on 291 unmarried women with a current
      unplanned pregnancy show that women with only one partner in the past year are
      older and are more likely to use the most effective contraceptive methods than
      are women who have more than one partner. Women with only one partner are also
      more likely to be solely responsible for decision-making about the choice of
      contraceptive methods, and are not as likely to use drugs in conjunction with
      sex. However, women with one partner are also less likely than others to use
      condoms or to protect in some other way against sexually transmitted diseases or
      the human immunodeficiency virus.

PMID- 8262171
TI  - Can condom users likely to experience condom failure be identified?
AB  - A study based on a convenience sample of 177 couples who each used 11 condoms
      found that 103 condoms (5.3%) broke before or during intercourse and 67 condoms
      (3.5%) slipped off during sex. Couples who had not used a condom in the past year
      were almost twice as likely to experience condom failure as were couples who had
      used at least one during that period (p < .001). Of the couples who had used a
      condom in the previous year, the failure rate among those who reported at least
      one condom break during that period was more than twice the failure rate among
      those who reported no breaks (p < .001). Among couples who had used condoms in
      the past year without breaking any, those who did not live with their partner and
      those who had a high school education or less were at increased risk of condom
      failure (adjusted odds ratios of 3.2 and 2.7, respectively).

PMID- 8262172
TI  - Comparison of contraceptive implant adopters and pill users in a family planning
      clinic in Baltimore.
AB  - All 133 women who began using the Norplant contraceptive implant between August
      and December of 1991 at a Planned Parenthood clinic in Baltimore were compared
      with a sample of 112 women who obtained prescriptions for the pill at the same
      clinic during the same time period. A multivariate analysis found that women of
      Medicaid are significantly more likely than those who are self-paying to select
      the implant rather than the pill. Similarly, compared with women who have had no
      children, those who have had two or more are also significantly more likely to
      choose the implant. However, adolescents and women who have had an abortion are
      no more likely than other women to select the implant.

PMID- 8262173
TI  - The restoration of abortion services at Cook County Hospital.

PMID- 8262174
TI  - Acceptability of dual method use.

PMID- 8262175
TI  - Molecular characterization of Phl p II, a major timothy grass (Phleum pratense)
      pollen allergen.
AB  - Grass pollen allergens belong to the most important and widespread elicitors of
      pollen allergy. Using serum IgE from a grass pollen allergic patient, a complete
      cDNA encoding a group II allergen was isolated from a timothy grass (Phleum
      pratense) pollen expression library. The deduced amino acid sequence of the Phl p
      II allergen shows an average sequence identity of 61% with the protein sequences
      determined for group II/III allergens from rye grass (Lolium perenne) and a
      sequence identity of 43% with the C-terminal portion of group I grass pollen
      allergens from different species. A hydrophobic leader peptide similar to leader
      peptides found in other major grass pollen allergens heads the deduced amino acid
      sequence, indicating that group II/III grass pollen allergens belong to a family
      of secreted proteins. Serum IgE specific for Phl p II, detected the protein
      exclusively in pollen and not in other plant tissues. The recombinant Phl p II
      was expressed in Escherichia coli and showed similar IgE-binding capacity as the
      natural allergen.

PMID- 8262176
TI  - Molecular basis for the different binding properties of benzodiazepines to human
      and bovine peripheral-type benzodiazepine receptors.
AB  - The 18 kDa peripheral benzodiazepine receptor (PBR) can be labelled by
      benzodiazepines, such as Ro5-4864, and isoquinoline carboxamides such as PK11195.
      These two compounds are reversible competitive inhibitors of each other. However,
      while the binding affinity of Ro5-4864 varies enormously across species, PK11195
      always displays high affinity, suggesting that their binding domains are
      overlapping but not identical. We report here that recombinant human and bovine
      PBR produced in yeast, a microorganism devoid of endogenous PBR, can be labelled
      with [3H]PK11195, but only the human receptor can be labelled with [3H]Ro5-4864.
      Furthermore, we identified, through the binding analysis of human-bovine
      chimaeric receptors, a region near the C-terminal end of the PBR, with only five
      non-conserved amino acids between human and bovine sequences, as responsible for
      the difference in high affinity binding of Ro5-4864 to the two receptors.

PMID- 8262177
TI  - Expression of a Drosophila GABA receptor in a baculovirus insect cell system.
      Functional expression of insecticide susceptible and resistant GABA receptors
      from the cyclodiene resistance gene Rdl.
AB  - Recombinant baculoviruses containing two alternative splice forms of the
      Drosophila Rdl GABA receptor gene were constructed. Spodoptera frugiperda (Sf21)
      cells infected with either splice form expressed a transcript of expected size
      (2.5 kb). Western blotting of cell membrane extracts and immunoprecipitation
      experiments with an anti-Rdl antiserum recognized a protein of the expected size
      of approximately 65 kDa. Whole cell patch clamp analysis of cells infected with
      either splice form revealed functional expression of GABA gated chloride ion
      channels which were blocked by application of 1 microM picrotoxinin. Following
      replacement of alanine 302 with a serine, a mutation associated with resistance
      to picrotoxinin and cyclodiene insecticides, mutant channels showed similar
      levels of insensitivity to picrotoxinin (approximately 100-fold) as those
      observed in recordings from cultured Drosophila neurons. The significance of the
      expression of an insect GABA receptor in an insect cell line and the similarity
      of the results from these functional expression studies to recordings from
      cultured neurons is discussed.

PMID- 8262178
TI  - Pectate lyase from Bacillus subtilis: molecular characterization of the gene, and
      properties of the cloned enzyme.
AB  - Pectate lyases (PL) initiate soft-rot diseases in plants by cleaving pectin which
      is the major component of the plant cell wall. The present paper reports the
      first cloning and characterization of a pectate lyase (pel) gene from the
      Bacillus genus. This gene was isolated from a Bacillus subtilis genomic library
      constructed in pUC18 as vector and Escherichia coli as host. By Southern
      hybridization this gene was shown to be present in a single copy in the B.
      subtilis genome. The nucleotide sequence of a 1.6 kb-pair HindIII restriction
      fragment, which confers pectate lyase activity to E. coli, indicated a 1,260 bp
      open reading frame encoding a 420 amino acid polypeptide which includes a 21
      amino acid signal sequence. The 45,605 Da deduced protein displays homologies to
      PLs from Erwinia chrysanthemi. The B. subtilis PL cloned in E. coli was located
      in the periplasm. It was purified to homogeneity in a one-step procedure from the
      E. coli periplasmic fluid after overproduction using the pT7 system. Biochemical
      properties of the purified enzyme were similar to those found for the PL isolated
      from B. subtilis extracellular media.

PMID- 8262179
TI  - Insight into the interactions between subunits I and II of the cytochrome c
      oxidase of the yeast Saccharomyces cerevisiae by means of extragenic
      complementation.
AB  - In yeast, revertants were selected from two respiratory deficient mutants
      carrying mutations in the catalytic subunits of cytochrome oxidase. From a mutant
      carrying a double mutation in the vicinity of the copper binding pocket in
      subunit II, two genetically independent revertants were obtained in which the
      same extragenic reversion mutation was observed, A147V, in the putative helix 4
      of subunit I. A comparison with revertants derived from the second deficient
      mutant, carrying the deficiency mutation, S140L, in the loop 3-4 of subunit I,
      provides additional data in favour of an interaction between helix 4 of subunit I
      and subunit II.

PMID- 8262180
TI  - Restricted mobility of the sole tryptophan in membrane-bound melittin.
AB  - In spite of numerous studies, there appears to be no consensus regarding the
      orientation and aggregation state of membrane-bound melittin. We report here the
      restricted environment of the sole tryptophan residue in membrane-bound melittin
      using environment-induced effects on the rates of solvent relaxation. When
      incorporated into unilamellar vesicles of dioleoyl-sn-glycero-3-phosphocholine
      (DOPC), melittin exhibits a red edge excitation shift (REES) of 5 nm. In
      addition, fluorescence polarization of melittin in the membrane shows both
      excitation and emission wavelength dependence. Taken together, these observations
      indicate that the tryptophan residue of melittin is located in a motionally
      restricted region in the membrane.

PMID- 8262181
TI  - Derivatives of thapsigargin as probes of its binding site on endoplasmic
      reticulum Ca2+ ATPase. Stereoselectivity and important functional groups.
AB  - The naturally occurring sesquiterpene lactone thapsigargin is a potent and
      selective inhibitor of SERCA ATPases, a family of Ca(2+)-pumping ATPases present
      in the endoplasmic reticulum of all mammalian cells. We have studied some of the
      molecular features of thapsigargin responsible for its inhibitory action towards
      these Ca2+ ATPases. A series of thapsigargin analogues were synthesised and their
      inhibitory potencies determined using the uptake of 45Ca2+ in bovine cerebellar
      microsomes as a sensitive marker of Ca2+ ATPase activity. An attenuation of the
      inhibitory potency relative to the parent compound was found ranging from slight
      to over 3 orders of magnitude. The inhibitory activity showed a very strong
      configuration dependence, a major contribution from the ester groups at C3 and
      C10, and an apparently minor contribution from the lactone ring substituents. The
      data are consistent with thapsigargin fitting to a sterically discriminating
      cleft involving the hydrophobic transmembrane region of the ATPase, and is
      compatible with available kinetic evidence of thapsigargin-mediated inhibition.

PMID- 8262182
TI  - Hydrolysis of small peptide substrates parallels binding of chymotrypsin
      inhibitor 2 for mutants of subtilisin BPN'.
AB  - Variants of subtilisin BPN' that possess improved specificity towards isoleucine
      compared with alanine at the P4 position of small peptide substrates, were
      analysed for their ability to bind chymotrypsin inhibitor 2. The binding of the
      inhibitor with isoleucine (wild-type) and with alanine as the P4 residue
      parallels the hydrolysis of tetrapeptide substrates. There is a linear
      relationship between the free energy of binding of the transition state of the
      substrate and the free energy of binding of the inhibitor with a slope of 2.0.
      The data suggest that the inhibitor uses predominantly ground state rather than
      transition state binding energy.

PMID- 8262183
TI  - Phosphorylation of a phosphoinositidase C-linked muscarinic receptor by a novel
      kinase distinct from beta-adrenergic receptor kinase.
AB  - Muscarinic receptor kinase activity previously described in intact CHO cells
      transfected with human m3-muscarinic receptor cDNA (CHO-m3 cells) [Tobin, A.B and
      Nahorski, S.R (1993) J. Biol. Chem. 268, 9817-9823] was found to be associated,
      at least in part, with a crude membrane fraction of CHO-m3 cell lysates.
      Phosphorylation of the m3-muscarinic receptor was agonist dependent, reaching a
      maximum after 10 min exposure to carbachol (1 mM) and was completely blocked by
      atropine (10 microM). m3-Muscarinic receptor phosphorylation was insensitive to
      Zn2+ (0.1 mM) and heparin (1 microgram/ml), concentrations that inhibit
      endogenous beta-adrenergic receptor kinase activity present in CHO-m3 cells
      strongly suggesting that the m3-muscarinic receptor kinase is distinct from beta
      adrenergic receptor kinase. A role for protein kinase C can also be eliminated on
      the basis that the potent protein kinase C inhibitor, Ro-318220 (1 microM), had
      no effect on agonist-mediated m3-muscarinic receptor phosphorylation. Further,
      the inability of calcium (300 microM), cAMP (0.2 mM) and cGMP (0.2 mM) to elevate
      the basal phosphorylation state of m3-muscarinic receptors eliminates a role for
      protein kinases regulated by these second messengers. Finally, agonist mediated
      phosphorylation appears to be independent of G-protein activation as both GDP
      beta-S (500 microM) and GTP-gamma-S (100 microM) did not influence m3-muscarinic
      receptor phosphorylation.

PMID- 8262184
TI  - Rat endopeptidase-24.18 alpha subunit is secreted into the culture medium as a
      zymogen when expressed by COS-1 cells.
AB  - Endopeptidase-24.18 (EC 3.4.24.18, E-24.18) is an oligomeric Zn-ectoenzyme. The
      alpha and beta subunits have been cloned from both rat and mouse kidneys. The
      primary structure of these subunits revealed that they both contain the consensus
      Zn binding site and that they are members of the astacin family. Analysis of the
      hydropathy plot also suggested that they are anchored by a C-terminal hydrophobic
      domain. In order to verify the mode of anchoring of the rat E-24.18 alpha subunit
      and to test the functionality of the astacin-like domain in the alpha subunit
      when expressed alone, COS-1 cells were transfected with a cloned cDNA for rat
      alpha subunit. Despite the presence of its putative transmembrane domain, the
      alpha subunit was not anchored in the plasma membrane but rather secreted as a
      dimer into the culture medium. When the enzymatic activity of the secreted
      recombinant protein was tested in the azocasein degradation assay, the alpha
      subunit was found to be inactive. Activity could, however, be revealed after mild
      trypsin digestion. This activity was abolished by replacing the Glu-157 in the
      active site by Val. Taken together our results suggest that the alpha subunit of
      Endopeptidase-24.18 contains a latent astacin-like Zn metallopeptidase activity
      which could be secreted as a soluble enzyme by kidney and intestine.

PMID- 8262185
TI  - Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha) from human small
      intestine and its expression in COS-1 cells.
AB  - PABA peptide hydrolase (PPH) from human enterocytes is comprised of two subunits,
      alpha and beta. PPH alpha is over 70% identical to meprin, a protease isolated
      from mouse and rat kidney. The enzyme shows a modular organization in that it
      contains an astacin protease domain, an adhesive domain, an EGF-like domain, an a
      putative C-terminal membrane spanning domain. Expression of a chimeric meprin-PPH
      alpha cDNA in COS-1 cells led to the synthesis of immature, transport-incompetent
      homodimers. In addition, complex glycosylated forms were detected in the culture
      medium, suggesting that the enzyme is secreted after proteolytic removal of the
      membrane anchor.

PMID- 8262186
TI  - Expression of the alpha subunit of PABA peptide hydrolase (EC 3.4.24.18) in MDCK
      cells. Synthesis and secretion of an enzymatically inactive homodimer.
AB  - In this paper, we report the expression of PPH alpha in the polarized cell line
      MDCK (Madin Darby canine kidney). In these cells, the enzyme was synthesized in
      an inactive proform, which upon treatment with trypsin was activated. The enzyme
      isolated from cell extracts was core-glycosylated and appeared to be retained in
      the ER as a homodimer. No PPH alpha was detectable on the surface of intact cells
      by immunofluorescence. However, a complex glycosylated soluble but inactive form
      was present in the culture medium, suggesting that proteolytic removal of the C
      terminal membrane anchoring peptide leads to the secretion of PPH alpha.

PMID- 8262187
TI  - Molecular analysis of SAR1-related cDNAs from a mouse pituitary cell line.
AB  - Vesicular transport between the endoplasmic reticulum (ER) and the Golgi in the
      yeast Saccharomyces cerevisiae requires a Ras-like, small GTP-binding protein,
      Sar1p [1-3]. Whether a functional homologue operates in export from the ER in
      mammalian cells is unknown, nor is it clear if transport in other branches of the
      secretory pathway requires member(s) of a gene family. In this study, we used a
      PCR approach to examine the complexity of SAR1-related sequences expressed in
      mammalian cells that possess multiple secretory pathways. Amplification of cDNA
      sequences from rodent pituitary cells with primers corresponding to two conserved
      GTP binding domains of Sar1p yielded several clones with sequences homologous to
      Sar1 and/or the closely related ADP-ribosylation factor (ARF) family. Of these,
      only two showed closer homologies to S. cerevisiae Sar1 than members of the ARF
      family and are designated as mSARa and mSARb. Northern blot analysis shows that
      mSARa is expressed in most tissues including liver, heart, brain, skeletal muscle
      and kidney. In contrast, mSARb is preferentially expressed in skeletal muscle and
      liver. The full-length cDNA of mSARa isolated from a mouse pituitary AtT-20 cDNA
      library encodes a protein of 198 amino acids, and is 61.6% identical to Sar1p
      from S. cerevisiae. Thus in contrast to the large rab family of GTP-binding
      proteins, vesicular transport in mammalian cells appears to be mediated by a
      relatively small number of Sar1-related proteins.

PMID- 8262188
TI  - A dynamical model for post-translational modifications of microtubules.
AB  - In many cases, post-translational modifications constitute indirect markers of
      non-dynamic microtubules. The correlation between stability of microtubular
      systems and post-translational modifications suggests that they may act as a
      signal in patterning mechanisms. However, a crucial question remains as to how
      the repertoire of distinctly modified microtubules is generated. We propose here
      an ubiquitous mechanism of spatial and temporal differentiation of microtubules.
      In this model, the diversity of post-translational modifications results from a
      dynamical pathway separation which is ensured by biochemical switches between
      self-regulated mechanisms of differentiation. Thus, it does not require any
      hypothetical subcellular compartmentalization of enzymatic activities responsible
      for the various post-translational modifications. These results are discussed in
      relation to experimental evidences for a temporal and spatial regulation of
      microtubule modifications.

PMID- 8262189
TI  - Comparison of properties of mistletoe lectin I A-chain and ricin B-chain
      conjugate with native toxins.
AB  - Chimeric toxin protein was prepared from the mistletoe lectin I A-chain and ricin
      B-chain by using the disulfide exchange reaction. Ricin and chimeric protein were
      indistinguishable in binding to immobilized asialofetuin in ELISA. Chimeric
      protein was more toxic to Jurkat cells than native mistletoe lectin I, but not so
      effective as native ricin. In the presence of NH4Cl, which enhances the toxicity
      of some toxins and immunotoxins, but does not influence ricin toxicity, both
      ricin and chimeric toxin had equal cytotoxic activity. The possibility is
      discussed that the ricin B-chain protects the ricin A-chain (RTA) from
      degradation during delivering RTA from the cell surface to the place where RTA is
      translocated into the cytosol.

PMID- 8262190
TI  - Solubilisation partial characterisation of the alpha-MSH receptor on primary rat
      Schwann cells.
AB  - The ACTH/MSH melanocortin core peptide sequence possesses neurotrophic properties
      in peripheral nerve. During functional neuroanatomical recovery after damage to
      peripheral nerves, Schwann cells play a significant role in facilitating
      regeneration. Here we employ a modified super-potent alpha-MSH analogue to
      solubilise alpha-MSH receptor proteins from cultured primary rat Schwann cells.
      [125I-Tyr2,Nle4,D-Phe7,ATB-Lys11]-alpha-MSH photoaffinity labelled proteins from
      Schwann cells were analyzed by SDS-PAGE followed by autoradiography. The results
      indicate that the alpha-MSH receptor proteins labelled have a molecular weight of
      42-45 kDa. These data are the first to demonstrate solubilisation and
      characterisation of alpha-MSH receptors from non-melanoma cells.

PMID- 8262191
TI  - Carcinogens stimulate phosphorylation of ethanolamine derived from increased
      hydrolysis of phosphatidylethanolamine in C3H/101/2 fibroblasts.
AB  - Many human tumors contain high concentrations of ethanolamine phosphate (EtnP).
      An important question is whether increased formation of EtnP is merely the
      consequence of cell transformation, or is it associated with the process of
      carcinogenesis. Here we show that in C3H/10T1/2 embryonic fibroblasts, an
      established cellular model for the study of carcinogenesis, the environmental
      carcinogens, 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (B[a]P)
      (0.1-1 microgram/ml concentration; 24 h treatment), stimulate phosphorylation of
      ethanolamine derived from increased hydrolysis of phosphatidylethanolamine. The
      results suggest that increased formation of EtnP is associated with the early
      stages of carcinogenesis. This observation may have prognostic value.

PMID- 8262192
TI  - Inhibition of PDGF BB stimulated DNA synthesis in rat aortic vascular smooth
      muscle cells by the expression of a truncated PDGF beta receptor.
AB  - Rat aortic vascular smooth muscle cells (VSMCs) were transfected with a vector
      encoding a truncated human PDGF beta receptor or the full-length human PDGF beta
      receptor. Cells stably expressing the truncated human PDGF beta receptor or the
      full-length human PDGF beta receptor were selected and the effect of PDGF BB on
      DNA synthesis in these cells was studied. Cells expressing the full-length PDGF
      beta receptor entered DNA synthesis normally, however, cells expressing the
      truncated PDGF beta receptor failed to enter DNA synthesis in response to PDGF
      BB. These data show that the mitogenic response of rat aortic vascular smooth
      muscle cells to PDGF BB can be inhibited by the expression of a truncated PDGF
      beta receptor.

PMID- 8262193
TI  - DnaK ATPase activity revisited.
AB  - It has recently been reported that the ATPase activity of DnaK, a 70 kDa heat
      shock protein from E. coli, is autostimulated by increasing protein concentration
      [(1993) FEBS Lett. 322, 277-279], suggesting that the DnaK dimer may be the
      enzymatically active species. In this paper we investigated the ATPase activity
      of different DnaK preparations; we found that the turnover number was very
      dependent on protein purification. With HPLC-purified DnaK we found a turnover
      number 20- to 50-fold lower than typical values previously published and no
      evidence of autostimulation, indicating that the monomer is the active species.

PMID- 8262194
TI  - Synthesis and farnesylation of a-factor fusion proteins in Saccharomyces
      cerevisiae.
AB  - We have generated in-frame fusions between the mouse dihydrofolate reductase
      (DHFR) and parts of the a-factor MFA1 gene to explore the potential of a-factor
      as a secretion signal for larger polypeptides. We demonstrated that the fusion
      proteins are farnesylated by comparing the mobility of fusion proteins prepared
      from a wild-type strain and a farnesyltransferase mutant (ste16/ram1) on SDS-gels
      and by an in vitro farneyslation assay. In contrast to unmodified DHFR, the
      fusion proteins could be sedimented from cell extracts by centrifugation.
      Solubilization experiments indicated that the highly hydrophobic a-factor moiety
      renders the fusion proteins insoluble, explaining why the fusions are not
      secreted into the culture medium.

PMID- 8262195
TI  - On the two iron centers of desulfoferrodoxin.
AB  - Desulfoferrodoxin from Desulfovibrio vulgaris, strain Hildenborough, is a
      homodimer of 28 kDa; it contains two Fe atoms per 14.0 kDa subunit. The N
      terminal amino-acid sequence is homogeneous and corresponds to the previously
      described Rho gene, which encodes a highly charged 14 kDa polypeptide without a
      leader sequence. Although one of the two iron centers, FeA, has previously been
      described as a 'strained rubredoxin-like' site, EPR of the ferric form proves
      very similar to that of the pentagonal bipyramidally coordinated iron in ferric
      complexes of DTPA, diethylenetriaminepentaacetic acid: both systems have spin S =
      5/2 and rhombicity E/D = 0.08. Unlike the Fe site in rubredoxin the FeA site in
      desulfoferrodoxin has a pH dependent midpoint potential with pKox = 9.2 and pKred
      = 5.3. Upon reduction (Em,7.5 = +2 mV) FeA exhibits an unusually sharp S = 2
      resonance in parallel-mode EPR. The second iron, FeB, has S = 5/2 and E/D = 0.33;
      upon reduction (Em,7.5 = +90 mV) FeB turns EPR-silent.

PMID- 8262196
TI  - Structural and functional characterisation of recombinant human erythropoietin
      analogues.
AB  - Deletion mutants of a synthetic human erythropoietin-cDNA were transiently
      expressed in COS-7 cells and products analyzed using Western blots and a cell
      proliferation assay. Only two mutants with deletions affecting the N-terminal
      portion and the amino acid sequence 115-121 displayed biological activity. The
      exchange of hydrophilic, charged amino acids by alanine in two potential alpha
      helical regions, the internal amino acid sequence 102-106 and the C-terminal
      sequence 154-159, causes a 2-11-fold loss of activity. The results suggest that
      both regions are involved in either maintaining the active structure of the
      hormone or interacting with the receptor.

PMID- 8262197
TI  - Modulation of mammalian cell proliferation by a modified tRNA base of bacterial
      origin.
AB  - Addition of the q-base to q-deficient non-transformed mammalian cells stimulated
      their proliferation. The q-base also improved proliferation of some cancer
      derived cell lines, but inhibited proliferation of others. The proliferation of
      HeLa-S3 carcinoma cells was stimulated by q under aerobic conditions, but was
      inhibited when the cells had shifted their energy metabolism towards glycolysis
      as the result of oxygen limitation. Q-deficient cells could not adapt their
      proliferation to the respective oxygen tension. The q-base stimulated the
      proliferation of non-transformed fibroblasts but inhibited proliferation of the
      same cell line, when aerobic glycolysis was increased after transformation with
      the ras gene. The results suggest that the q-base permits mammalian cells to
      adapt their proliferation to their specific metabolic state.

PMID- 8262199
TI  - Crystallization and crystallographic investigations of ribonucleotide reductase
      protein R1 from Escherichia coli.
AB  - Crystals of Escherichia coli ribonucleotide reductase protein R1 have been grown
      in complex with a synthetic peptide corresponding to the carboxyl end of protein
      R2. Good quality crystals could only be obtained after improvement of the
      purification protocol and are of the space group R32 with hexagonal cell axes a =
      b = 226 A and c = 341 A. They contain 3 subunits per asymmetric unit and diffract
      to 2.5 A resolution in synchrotron radiation. A multiple isomorphous replacement
      map at 5.5A, improved by solvent flattening, shows that the dimeric molecules are
      elongated, about 110 A long. The dimer is thin in the middle around the molecular
      two-fold axis. The subunit is shaped like a bowl, probably with the active site
      in its center.

PMID- 8262198
TI  - The MAP kinase-activated protein kinase 2 contains a proline-rich SH3-binding
      domain.
AB  - The protein sequence of MAP kinase-activated protein kinase 2 (MAPKAP kinase 2)
      deduced from mouse cDNA sequence reveals structural features of the enzyme, which
      could be of importance for its function: a proline-rich SH3-binding domain N
      terminal to the catalytic region, a MAP kinase phosphorylation site and a
      bipartite nuclear targeting sequence located C-terminal to the catalytic region.
      The catalytic domain itself has the strongest homology to calcium/calmodulin
      dependent protein kinase II. Northern blot analysis demonstrates a 3.5 kb MAPKAP
      kinase 2 transcript which is ubiquitously expressed and, hence, co-expressed with
      the mRNA of the recently identified substrate Hsp25 in all tissues analysed.
      However, the functional consequences of the nuclear targeting sequence present in
      MAPKAP kinase 2 suggest the existence of further substrates for the enzyme in the
      nucleus.

PMID- 8262200
TI  - Volume-regulatory taurine release from a human lung cancer cell line. Evidence
      for amino acid transport via a volume-activated chloride channel.
AB  - Exposure of a human lung epithelial cancer cell-line to hypo-osmotic media led to
      a marked increase in the rate of efflux from the cells of taurine, a non
      essential sulfonic amino acid. The osmotically-activated taurine efflux was
      inhibited by a range of known Cl- channel blockers, the most potent of which were
      NPPB and 1,9-dideoxyforskolin. These reagents were similarly effective at
      inhibiting the osmotically-activated efflux of I-, a known substrate of volume
      activated Cl- channels. The results are consistent with the hypothesis that
      volume-regulatory taurine release from these cells is mediated by a volume
      activated Cl- channel.

PMID- 8262201
TI  - Function of saposin C in the reconstitution of glucosylceramidase by
      phosphatidylserine liposomes.
AB  - The function of saposin C (Sap C), a glucosylceramidase activator protein, in the
      enzyme stimulation by phosphatidylserine (PS) liposomes has been investigated.
      Using gel filtration experiments evidence was obtained for Sap C binding to PS
      large unilamellar vesicles (LUV) but not to glucosylceramidase. PS LUV, which by
      themselves are unable to tightly bind and stimulate the enzyme, acquire the
      capacity to also bind the enzyme after interaction with Sap C, making it express
      its full activity. Our results indicate that the primary step in the Sap C mode
      of action resides in its association with PS membranes; in turn, this association
      promotes the interaction between the membranes and glucosylceramidase.

PMID- 8262202
TI  - High-level expression of functional cGMP-dependent protein kinase using the
      baculovirus system.
AB  - The understanding of the structure and function of cGMP-dependent protein kinase
      (cGMP kinase) has been hindered by the difficulty to obtain large quantities of
      functional enzyme. A recombinant baculovirus encoding bovine cGMP kinase I alpha
      was constructed and purified. Infected insect cells synthesized large amounts of
      soluble and biologically active cGMP kinase I alpha representing up to 10% of the
      total cell extract protein. The recombinant enzyme had an identical apparent
      molecular mass, cGMP affinity and kinase activity as the native bovine lung
      enzyme. The high-level expression of functional cGMP kinase I alpha should
      provide an excellent tool to study further the structure and function of cGMP
      kinase.

PMID- 8262203
TI  - Deletion of NH2- and COOH-terminal sequences destroys function of the Ca2+ ATPase
      of rabbit fast-twitch skeletal muscle sarcoplasmic reticulum.
AB  - Deletion mutants of the Ca2+ ATPase of rabbit fast-twitch skeletal muscle
      sarcoplasmic reticulum (SERCA1a) were constructed and expressed in COS-1 cells.
      The mutants were expressed at levels 7- to 15-fold lower than the wild-type and
      were inactive. In vitro transcription-translation-insertion experiments showed
      that deletion of transmembrane sequences M1 and M2, but not of M8, M9, M10 or the
      NH2-terminal 30 amino acids inhibited the stable insertion of the enzyme into the
      membrane. Thus there was no correlation between loss of function and membrane
      insertion. A signal sequence for membrane insertion may exist in M1 and M2.

PMID- 8262204
TI  - mRNA amplification system by viral replicase in transgenic plants.
AB  - We have constructed transgenic tobacco plants (M1x2-FCP2IFN plants) expressing
      viral RNA replication genes of brome mosaic virus (BMV) and BMV RNA3 derivative
      (FCP2IFN) carrying the human gamma interferon (IFN-gamma) gene. In M1x2-FCP2IFN
      plants the RNA3 derivative expressed from the integrated cDNA was replicated and
      subgenomic RNA (i.e. mRNA of IFN-gamma) was produced by BMV replicase. The
      accumulation level of the mRNA of IFN-gamma was approximately 5-fold higher than
      that by the cauliflower mosaic virus (CaMV) 35S RNA promoter. In addition IFN
      gamma accumulated in M1x2-FCP2IFN plants.

PMID- 8262205
TI  - Functional characterization of the catalytic site of the tetanus toxin light
      chain using permeabilized adrenal chromaffin cells.
AB  - The molecular events underlying the inhibition of exocytosis by tetanus toxin
      were investigated in permeabilized adrenal chromaffin cells. We found that
      replacement of amino acid residues within the putative zinc binding domain of the
      tetanus toxin light chain such as of histidine (position 233) by cysteine or
      valine, or of glutamate (position 234) by glutamine completely abolished the
      effect of the light chains on Ca2+ induced catecholamine release. Dipicolinic
      acid, a strong chelating agent for zinc, also prevented the effect of the tetanus
      toxin light chain. Zn2+ and, less potently Cu2+ and Ni2+, but not Cd2+ and Co2+,
      restored the activity of the neurotoxin. These data show that zinc and the
      putative zinc binding domain constitute the active site of the tetanus toxin
      light chain. Neither captopril, an inhibitor of synaptobrevin cleavage nor
      peptides spanning the site of synaptobrevins cleaved by the tetanus toxin in
      neurons, prevented the inhibition of Ca2+ induced catecholamine release by the
      tetanus toxin light chain. This suggests that synaptobrevins are not a major
      target of tetanus toxin in adrenal chromaffin cells.

PMID- 8262206
TI  - Electron microscopy of two-dimensional crystals of mitochondrial ATP synthase.
AB  - Two-dimensional crystals of the mitochondrial ATP synthase up to 0.4 microns in
      size were obtained from the detergent-lipid-protein micelles by detergent
      dialysis. A projected map of the negatively stained crystal was calculated from
      electron microscopical images by the Fourier-filtering procedure at about 2.8 nm
      resolution. The unit cell (with not more than two ATP synthase molecules) has the
      following parameters: a = 13.0 nm, b = 25.6 nm and gamma = 86 degrees. Two
      alternative models for the crystal structural organization were suggested, viz.
      with one or two protein molecules per unit cell.

PMID- 8262207
TI  - The molecular basis of UV-induced mutagenicity of sunscreens.

PMID- 8262208
TI  - The cancer cell, from the inside out.

PMID- 8262209
TI  - Antibodies against the major brain isoforms of 14-3-3 protein: an antibody
      specific for the N-acetylated amino-terminus of a protein.

PMID- 8262210
TI  - Histone acetylation and gene induction in human cells.
AB  - An antibody recognising acetylated core histones was used to immunoprecipitate
      chromatin fragments from proliferating human K562 cells and from cells induced to
      differentiate with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA).
      The DNA of the acetylated chromatin was probed with sequences of platelet derived
      growth factor B chain (PDGF-B), a gene which is induced to strong expression upon
      differentiation. A high level of acetylation was observed before gene induction
      and no change seen following induction. This implies that core histone
      acetylation is an essential precondition for transcription.

PMID- 8262211
TI  - Structure and organization of the gene encoding a mouse mitochondrial stress-70
      protein.
AB  - We have previously found that an antigenic protein specific for C3H strain mouse
      (C3H strain-specific antigen, CSA) is identical to peptide-binding protein 74
      (PBP74). PBP74/CSA is a novel member of the stress-70 protein family in
      mitochondria. In this study, mouse genomic clones encoding PBP74/CSA, including
      the 5'- and 3'-flanking regions of the gene, have been isolated and sequenced.
      The PBP74/CSA gene contained 17 exons interrupted by 16 introns. Two dimeric
      repeats of the consensus sequence of the heat-shock element are present in the 5'
      flanking region of the PBP74/CSA gene. Moreover, the first intron is interrupted
      within the amino-terminal leader sequence, the pattern of which is similar to
      that of cytochrome c1 located in the mitochondria.

PMID- 8262212
TI  - Proteasome and cell cycle. Evidence for a regulatory role of the protease on
      mitotic cyclins in yeast.
AB  - The cell cycle of eukaryotic cells is strictly regulated. This regulation is
      performed by a serine/threonine kinase. The different functions of this kinase in
      the cell cycle are modulated by different cyclins, which fluctuate in
      concentration ('cycle') during the different stages of the cell cycle. Using
      yeast as a model organism we show here that the activity of the multifunctional
      proteinase, the proteasome, is directly connected to the function of the mitotic
      cyclin Clb2. Our studies indicate that the proteasome is the proteolytic
      regulator of this cyclin and thus a central regulator of the cell cycle.

PMID- 8262213
TI  - Okadaic acid-sensitive protein phosphatases dephosphorylate MARCKS, a major
      protein kinase C substrate.
AB  - The myristoylated alanine-rich C kinase substrate (MARCKS) undergoes a rapid and,
      in certain circumstances, transient increase in phosphorylation in response to
      stimuli that activate protein kinase C. We have investigated the protein
      serine/threonine phosphatase activity responsible for reversing the
      phosphorylation of MARCKS. In cell-free assays, protein phosphatases 1, 2A and 2C
      (PP1, PP2A and PP2C) all dephosphorylate recombinant MARCKS or a synthetic
      peptide based on its phosphorylation site domain. In intact Swiss 3T3 cells,
      okadaic acid, a specific inhibitor of PP1 and PP2A, had little effect on MARCKS
      phosphorylation on its own, but largely prevented the dephosphorylation of MARCKS
      that occurred following activation of protein kinase C by bombesin with
      subsequent receptor blockade. These results indicate that although the
      dephosphorylation of MARCKS can be mediated by PP2C in vitro, this protein is
      dephosphorylated by okadaic acid-sensitive phosphatases in the intact cell.

PMID- 8262214
TI  - A mutation causing constitutive synthesis of the pyruvate dehydrogenase complex
      in Escherichia coli is located within the pdhR gene.
AB  - The aceE-aceF-lpd genes encoding the pyruvate dehydrogenase (PDH) complex of
      Escherichia coli are preceded by a gene encoding a putative transcriptional
      regulator, PdhR (formerly designated GenA). Enzymological tests and studies with
      pdhR-lacZ and aceE-lacZ translational fusions have shown that a constitutive
      mutation (acec816), which increases PDH complex synthesis to the pyruvate-induced
      level in the absence of inducer, is recessive to the wild-type pdhR gene in
      trans. Sequence comparisons further showed that the acec816 mutation affects a
      single site in the pdhR gene leading to an Arg118 (CGU)-->Cys (UGU) substitution
      in the PdhR protein. The results support the view that synthesis of the PDH
      complex is regulated from the pdhR promoter of a pdhR-aceEF-lpd operon.

PMID- 8262215
TI  - The mechanism of Ba(2+)-induced exocytosis from single chromaffin cells.
AB  - Dialysis of Ba2+ into voltage-clamped single bovine chromaffin cells produced a
      concentration-dependent increase in cell capacitance, reflecting an enhanced rate
      of exocytotic events. Between 0.1 and 1 mM, Ba2+ linearly increased both the rate
      and the total amount of exocytosis. In unclamped cells also, extracellular Ba2+
      induced the release of catecholamines, as assayed with a carbon-fibre electrode
      in the amperometric mode. Additionally, extracellular application of Ba2+
      increased the apparent internal Ca2+ concentration ([Ca2+]app) in fura-2-loaded
      chromaffin cells. These observations were made both in the presence and absence
      of external Ca2+ (Cao2+), as well as after depletion of the intracellular Ca2+
      stores with ionomycin. Under current-clamp conditions, Ba2+ induced pronounced
      depolarization of the cells. These results are compatible with the following
      conclusions: by blocking K+ channels, Ba2+ causes depolarization of chromaffin
      cells. This results in opening of voltage-gated Ca2+ channels and Ba2+ entry into
      the cytosol. Ba2+ then directly triggers exocytotic events, although it induces
      exocytosis only at concentrations more than a 100-fold higher than Ca2+. Various
      effects contribute to the generally observed greater secretory responses with
      Ba2+ as compared with Ca2+; these are the depolarizing effects of extracellular
      Ba2+, its greater entry through non-inactivating Ca2+ channels and its poor
      intracellular buffering largely arising from its weak affinity for plasmalemmal
      Ca2+ extrusion mechanisms. In some cases, Ba2+ additionally induces release of
      Ca2+ from internal stores, as evidenced by its effect on fura-2 fluorescence at
      different wavelengths.

PMID- 8262216
TI  - Production of disulfide-linked hirudin dimer by in vitro folding.
AB  - A simple process of in vitro folding has been developed for the preparation of
      hirudin dimer. A variant of recombinant hirudin with Asp33 replaced by Cys was
      expressed in yeast and isolated by HPLC. Crude Cys33-hirudin contains
      heterogeneous products that are made of one species of primary sequence. They
      were together reduced/denatured, and allowed to re-fold in the sodium bicarbonate
      buffer (pH 8.3) alone. Active, homogeneous Cys33-hirudin monomer folded
      spontaneously with a first order rate constant of 0.05 +/- 0.01 min-1, followed
      by the oxidation of two Cys33 to produce the pure dimer. The folding yield was
      90%. On an equal weight basis, both Cys33-hirudin monomer and the dimer exhibit
      thrombin inhibitory activity comparable to that of wild-type hirudin. Due to the
      presence of an extra cysteine, the folding of active hirudin monomer (formation
      of three native disulfides) was accelerated by at least 12-fold.

PMID- 8262217
TI  - A role for central A3-adenosine receptors. Mediation of behavioral depressant
      effects.
AB  - The behavioral effects of a selective A3 adenosine receptor agonist 3-IB-MECA (N6
      (3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) in mice and the localization of
      radioligand binding sites in mouse brain were examined. Low levels of A3
      adenosine receptors were detected in various regions of the mouse brain
      (hippocampus, cortex, cerebellum, striatum), using a radioiodinated, high
      affinity A3-agonist radioligand [125I]AB-MECA (N6-(3-iodo-4-aminobenzyl)-5'-N
      methylcarboxamidoadenosine). Scatchard analysis in the cerebellum showed that the
      Kd value for binding to A3 receptors was 1.39 +/- 0.04 nM with a Bmax of 14.8 +/-
      2.1 fmol/mg protein. 3-IB-MECA at 0.1 mg/kg i.p. was a locomotor depressant with
      > 50% reduction in activity. Although selective A1 or A2a antagonists reversed
      locomotor depression elicited by selective A1 or A2a agonists, respectively, the
      behavioral depressant effects of 3-IB-MECA were unaffected. 3-IB-MECA also caused
      scratching in mice, which was prevented by coadministration of the histamine
      antagonist cyproheptadine. The demonstration of a marked behavioral effect of A3
      receptor activation suggests that the A3 receptor represents a potential new
      therapeutic target.

PMID- 8262218
TI  - Proprotein processing activity and cleavage site selectivity of the Kex2-like
      endoprotease PACE4.
AB  - Proprotein processing activity of the Kex2-like mammalian endoprotease PACE4 and
      its cleavage selectivity for sites with basic amino acid residues were
      determined. Using a recombinant vaccinia virus-based expression system, PACE4 was
      expressed in pig kidney PK(15) cells and, like two other Kex2-like endoproteases
      furin and PC6A, shown to correctly process the precursor of von Willebrand factor
      (pro-vWF). Furthermore, characteristics of the cleavage site selectivity of PACE4
      were compared to those of furin and PC6A using the vWF cleavage site mutants vWFR
      1G, vWFK-2A, and vWFR-4A as substrates. Cleavage site selectivity of PACE4 and
      PC6A appeared to be similar but they differed from that of furin.

PMID- 8262219
TI  - Region-specific expression of multiple lactase-phlorizin hydrolase genes in
      intestine of rabbit.
AB  - We have identified a total of 4 sequences coding for lactase-phlorizin hydrolase
      (LPH) in the rabbit. Individual rabbits each yielded three different LPH cDNA
      sequences, or three chromosomal segments containing exon 1 of the LPH gene,
      representing either three genes or allelic variants of two genes. The three
      sequences were found in differing proportions in intestinal mRNA depending on the
      position along the small intestine from which the RNA was isolated. If all these
      mRNAs are translated, posttranslational mechanisms previously implicated in the
      regulation of LPH in the rabbit will be acting on different enzyme species in
      different parts of the intestine. However, we find no evidence for more than one
      LPH gene in the rat, and have previously shown that humans have only one LPH
      gene.

PMID- 8262220
TI  - Cytochrome d induction in Escherichia coli growing under unfavorable conditions.
AB  - Growth of E. coli in the presence of the protonophorous uncoupler
      pentachlorophenol is shown to strongly enhance levels of cytochrome d, a putative
      Na(+)-motive oxidase. This effect was found to be arrested by chloramphenicol and
      stimulated by high Na+ concentration in the growth medium. The induction of
      cytochrome d takes place in a mutant deficient in the F0F1 ATP-synthase but does
      not occur in mutants deficient in either of two different components of the Arc
      system. Similar relationships were revealed when pentachlorophenol was replaced
      by ferricyanide and phenazine methosulfate, agents oxidizing the respiratory
      chain. Induction of cytochrome d is also shown to occur in riboflavin-deficient
      mutants growing in the presence of such low riboflavin concentrations as to be
      insufficient to maintain a high respiration rate. It is suggested (i) that it is
      delta mu H+ decrease rather than reduction of the respiratory chain that is the
      signal for the induction of cytochrome d, and (ii) the Arc system is involved in
      this type of metabolic regulation.

PMID- 8262222
TI  - Induction of stathmin mRNA during liver regeneration.
AB  - Stathmin is a 19 kDa phosphoprotein, and is proposed to play a role in signal
      transduction in response to various extracellular stimuli that promote cellular
      growth and/or differentiation. We examined stathmin mRNA expression during
      development and liver regeneration in mice. Stathmin mRNA expression declined
      during the post-natal period and was undetected in adult liver. 36 h after
      partial hepatectomy, stathmin mRNA was rapidly induced and remained at elevated
      levels for at least 10 days. In situ hybridization experiments confirmed that
      stathmin mRNA expression occurred in hepatocytes. These results indicate that the
      stathmin gene expression appears to be repressed during the post-natal liver
      development, and is de-repressed by liver regeneration, which suggests that
      stathmin may be a good molecular marker of liver plasticity.

PMID- 8262221
TI  - Primary structure of cryX**, the novel delta-endotoxin-related gene from Bacillus
      thuringiensis spp. galleriae.
AB  - A cry-related sequence, designated cryX (EMBL X75019), was localized upstream of
      cryIG, the delta-endotoxin gene cloned from spp. galleriae of Bacillus
      thuringiensis and sequenced earlier [(1991) FEBS Lett. 293, 25-28]. Analysis of
      the cryX complete nucleotide sequence enabled us to explain its virtual
      crypticity and to reveal the chimeric structure of the genes, cryX and cryIG. The
      amino acid sequence of 1,151 residues encoded by the continuous reading frame of
      cryX is similar to the other delta-endotoxins but differs essentially from them.

PMID- 8262223
TI  - Catalytic and activating protons follow different pathways in the H(+)-ATPase of
      potato tuber mitochondria.
AB  - The effect of some F0F1 inhibitors on the activation of the H(+)-ATPase by the
      electrochemical proton gradient was investigated in mitochondria extracted from
      potato tubers. Transient activated state of the ATPase was revealed by addition
      of ATP and of the detergent lauryldimethylamine oxide (LDAO) to energized
      mitochondria. Venturicidin, tri-n-butyltin and aurovertin at high concentrations
      did not affect the process of delta mu H(+)-activation, whereas oligomycin fully
      blocked it. The results support the idea of separate pathways or binding sites
      for catalytic and activating protons.

PMID- 8262224
TI  - Effects of amino-terminus truncation in human cytochrome P450IID6 on its
      insertion into the endoplasmic reticulum membrane of Saccharomyces cerevisiae.
AB  - A truncated form of cytochrome P450IID6 deprived of 22 NH2-terminal amino acids
      residues (P450IID6 delta 1-22) was found in both the cytosol and the microsomal
      fraction of the yeast, Saccharomyces cerevisiae. A reduced CO difference spectrum
      of this form was characterized by the absence of absorption at 448 nm and weak
      absorption at 420 nm. Another peculiarity of P450IID6 delta 1-22 expression was
      its reduced content in the yeast cells compared to that of P450IID6, with the
      intracellular levels of the corresponding mRNAs being the same. We suggest that
      the deleted form of P450IID6, i.e. lacking 22 NH2-terminal amino acid residues,
      is not inserted properly in the endoplasmic reticulum membrane: it does not take
      up the proper conformation to enable normal heme binding and is degraded in the
      yeast cells.

PMID- 8262225
TI  - A threshold membrane potential accounts for controversial effects of fatty acids
      on mitochondrial oxidative phosphorylation.
AB  - The uncoupling effect of free fatty acids on oxidative phosphorylation in
      mitochondria has been known for more than 35 years. The mechanism of action,
      however, remains controversial. In this report the physicochemical basis of
      uncoupling was elucidated by studying the effect of free fatty acids on the
      proton permeability and membrane potential of proteoliposomes containing
      reconstituted cytochrome c oxidase (COX). A threshold membrane potential of about
      125 mV was identified for fatty acid-induced proton permeability. Only above this
      potential do free fatty acids translocate protons across the biological membrane.
      The data explain the controversial effects of long-chain fatty acids on oxidative
      phosphorylation as well as their role on non-shivering thermogenesis in larger
      mammals.

PMID- 8262226
TI  - Subunit III of the chloroplast ATP-synthase can form a Ca(2+)-binding site on the
      lumenal side of the thylakoid membrane.
AB  - Subunit III, the 8 kDa component of the chloroplast CFo H+ channel, was isolated
      and purified from pea thylakoids for the purpose of studying its Ca(2+)-binding
      properties. After n-butanol extraction and ether precipitation, HPLC purification
      was accomplished using a poly(styrene-divinylbenzene) column which removes lipid
      and protein contaminations. The main components of protein contamination were two
      hydrophobic proteins of near 4 kDa molecular mass, the psaI and psbK gene
      products associated with PSI and PSII reaction centers, respectively. Purified
      subunit III as well as the unfractionated organic-solvent soluble preparation
      were used in a 45Ca(2+)-ligand blot assay known to detect high affinity Ca(2+)
      binding sites in proteins. Polypeptides were separated with SDS-PAGE and were
      transferred onto PVDF membranes. Treatment of the membrane with 45CaCl2 in the
      presence of 10-fold excess of MgCl2 and 200-fold excess KCl led to the labeling
      of only the 8 kDa polypeptide. The Ca2+ binding was inhibited after derivatizing
      aqueously exposed carboxyl groups with a water soluble carbodiimide plus a
      nucleophile, after de-formylation of the N-terminal methionine, or with a
      subsequent treatment with La3+. Ca2+ binding was maximum at pH 7.5-8.5 and was
      greatly decreased at acidic pH. Dicyclohexylcarbodiimide treatment (no
      nucleophile was added) of thylakoid membranes, which derivatizes the
      hydrophobically located Glu-61, decreased the electrophoretical mobility of
      isolated subunit III but did not inhibit the Ca2+ binding. The data indicate that
      the carbonyl group of the formylated N-terminal Met-1 and probably the carboxyl
      group of the subunit III C-terminal Val-81 provide some of seven essential oxygen
      ligands normally required for defining a Ca(2+)-binding site in proteins. It is
      probable, but not yet established that an oligomeric form of subunit III
      polypeptides is essential for forming the Ca(2+)-binding site. Based on the
      accepted models for the hairpin conformation of the subunit III, it does seem
      clear that the Ca(2+)-binding site can form on the lumenal side of the membrane
      in the functional CFo structure.

PMID- 8262227
TI  - Protein kinase A modulates an endogenous calcium channel, but not the calcium
      activated chloride channel, in Xenopus oocytes.
AB  - In Xenopus oocytes, Ca2+ influx through an endogenous voltage-gated Ca2+ channel
      activates a transient outward Cl- current (ICl(Ca)), which is potentiated by cAMP
      increase. The site of cAMP effect appears to be the Ca2+ channel instead of the
      Ca(2+)-activated Cl- channel, because cAMP potentiates the Ba2+ current through
      the Ca2+ channel in a similar way to the ICl(Ca), and cAMP does not potentiate
      the Ca(2+)-dependent Cl- current in cells treated with Ca2+ ionophore. Using the
      catalytic subunit of protein kinase A (PKA) and PKA inhibitors, it was shown that
      PKA is both necessary and sufficient for the cAMP effect on ICl(Ca). Furthermore,
      the cAMP/PKA-mediated potentiation of ICl(Ca) was inhibited by both type 1 and
      type 2A protein phosphatases.

PMID- 8262229
TI  - Adhesive interactions of neutrophils and leukotriene synthesis.
AB  - Cell-substrate and cell-cell adhesion of neutrophils has been found to slow down
      the calcium ionophore A23187-induced synthesis of 5-lipoxygenase (5-LO)
      metabolites of arachidonic acid. Addition of the exogenous substrate, arachidonic
      acid (AA), together with A23187, resulted in the enhanced production of
      leukotriene B4 (LTB4) and 5-hydroxyeicosatetraenoic acid (5-HETE) by adherent
      neutrophils in comparison with those by the cells in suspension. We observed also
      the enhanced production of 5-LO metabolites in attached cells when we stimulated
      the cells by the combined action of phorbol 12-myristate 13-acetate (PMA) and
      A23187. Thus, the adhesion to solid substrate and to other cells, an important
      regulatory factor for the activity of many cells, is a powerful regulator of
      leukotriene production by neutrophils.

PMID- 8262228
TI  - Thioredoxin reduction dependent on alpha-ketoacid oxidation by alpha-ketoacid
      dehydrogenase complexes.
AB  - The pyruvate and alpha-ketoglutarate dehydrogenase complexes isolated from pig
      heart mitochondria promote the reduction of thioredoxin in the presence of their
      alpha-ketoacid substrates, coenzyme A, and free lipoate. Substrate-specific
      generation of reduced thioredoxin was established by two independent methods,
      viz. reduction of insulin and thioredoxin reductase-catalyzed NADPH formation.
      Dihydrolipoate accumulating in the absence of NAD+ is the likely intermediate. A
      redox function in alpha-ketoacid oxidation provides a potential role for the
      specific thioredoxins previously identified by us in mitochondria.

PMID- 8262230
TI  - Modulation of functional activities of the neurotoxin from black widow spider
      venom.
AB  - We have studied the action of an alpha-latrotoxin (alpha-LTX) complex of two
      polypeptides (LTX 130 kDa and low molecular weight protein (LMWP) 8 kDa) and the
      action of a venom fraction containing LTX with excess LMWP on calcium influx into
      synaptosomes and PC12 cells as well as on [14C]GABA release from synaptosomes.
      Both preparations considerably activate calcium influx and stimulate [14C]GABA
      release from synaptosomes. Preincubation of both preparations with antibodies
      against a 14 amino acid residue C-terminal peptide of LMWP differentially
      modulates these effects. Antibodies inhibit induced calcium influx and enhance
      induced GABA release.

PMID- 8262231
TI  - SH-containing compounds as allosteric effectors of glyceraldehyde-3-phosphate
      dehydrogenase.
AB  - The rate of hydrolysis of 3-phosphoglyceroyl-holoenzyme, a covalent intermediate
      of glyceraldehyde-3-phosphate dehydrogenase catalyzed reaction, is considerably
      decreased in the presence of micromolar concentrations of reduced glutathione,
      cysteine or dithiothreitol with Ki values of 0.78 microM, 0.6 microM and 10
      microM, respectively. The maximal effect is achieved at a molar ratio
      [effector]/[tetrameric enzyme] close to unity, which points to subunit
      cooperatively involved in the stabilization of the covalent intermediate against
      hydrolysis. The effect is specific for acylholoenzyme conformation and
      insignificant in the case of hydrolysis of acylated apoenzyme species. The
      ability of the effectors to stabilize the reaction intermediate against
      spontaneous hydrolysis, in which water replaces inorganic phosphate as the acyl
      group acceptor, may be a factor contributing to the specificity and effectiveness
      of the enzyme catalysis.

PMID- 8262232
TI  - Time-resolved study of tryptophan fluorescence in vesicle reconstituted
      cytochrome oxidase. Effect of redox transition.
AB  - Time-resolved study of fluorescence decay of the tryptophan residue in bovine
      cytochrome c oxidase in phospholipid vesicles is reported for the first time. The
      effect of the redox state of the protein on its conformation has been
      investigated using time-resolved decay of tryptophan fluorescence in the oxidised
      and reduced protein. The fluorescence decay was best fitted using a discrete
      three exponential model. Amplitude distribution of lifetimes also showed three
      distinct regions in the analysis of decay profiles by the maximum entropy method
      (MEM). Results of the time resolved studies showed that the amplitudes as well as
      the lifetimes of the tryptophan fluorescence remain the same for the oxidised and
      the reduced states of cytochrome c oxidase, indicating that the environment
      around tryptophan residues remains more or less unaltered on reduction of the
      protein. The results suggest that there is no global conformational change in the
      protein on electron transfer and support the possibility of the existence of
      local fluctuations in the protein during the redox cycle.

PMID- 8262233
TI  - Active increase in cardiolipin synthesis in the stationary growth phase and its
      physiological significance in Escherichia coli.
AB  - Activity of the Escherichia coli cardiolipin synthase, encoded by cls, increased
      about 10-fold in the stationary growth phase, while other committed-step enzymes
      in phospholipid biosynthesis rather decreased. A null cls mutant lost viability
      to 10(-4) of the wild-type cells during the prolonged incubation for 5 days.
      Cardiolipin was most stable among membrane phospholipids during the incubation.
      Accordingly, cardiolipin should play a role in survival of the cell and E. coli
      employs a sophisticated way to form cardiolipin according to need even under non
      growing conditions.

PMID- 8262234
TI  - The unusual rps3-like orf712 is functionally essential and structurally conserved
      in Chlamydomonas.
AB  - The Chlamydomonas reinhardtii chloroplast orf712 is a previously described open
      reading frame that lacks a detectable transcript but potentially encodes a
      polypeptide with sequence similarities to ribosomal protein Rps3 only at its N-
      and C-termini. Here we report that orf712 is an essential gene, as demonstrated
      through gene disruption by particle gun-mediated chloroplast transformation. We
      also show that an orf712 is present and structurally conserved in all of the two
      or three major Chlamydomonas lineages. Our results suggest that orf712 is an
      unusual rps3 gene that contains a large translated intervening sequence.

PMID- 8262235
TI  - In vivo affinity label of a protein expressed in Escherichia coli. Coenzyme A
      occupied the AT(D)P binding site of the mutant F1-ATPase beta subunit (Y307C)
      through a disulfide bond.
AB  - When Tyr-307 of the beta subunit of F1-ATPase from a thermophilic Bacillus strain
      PS3 is replaced by cysteine and expressed in Escherichia coli cells, about a half
      population of the mutant beta subunit are labeled by Coenzyme A at Cys-307
      through a disulfide bond which is cleavable by reducing treatment. The mutant
      beta subunit can be reconstituted into the alpha 3 beta 3 complex of which ATPase
      activity is stimulated two-fold by reducing treatment either prior or after
      reconstitution. Since Tyr-307 has been supposed to be located at one of
      subdomains which form the ATP binding site of the beta subunit, Coenzyme A binds
      to the mutant beta subunit as an AT(D)P analogue in E. coli cells and then
      covalently attaches to Cys-307.

PMID- 8262236
TI  - Crystallization and preliminary X-ray analysis of leukemia inhibitory factor.
AB  - Leukemia inhibitory factor (LIF) is a polyfunctional molecule with significant
      and diverse biological activities. LIF is a glycoprotein secreted by a number of
      different cell types in vitro. It is induced in fibroblasts, lymphocytes,
      monocytes and astrocytes by various inducers such as serum, TNF, interleukin-IP
      and EGF. Due to extensive and variable glycosylation the molecular weight can
      range from 38 to 67 kDA. The biological functions of LIF are mediated through a
      receptor and a signal transducer, gp130, which is also used by factors like
      interleukin-6 (IL-6), cilliary neurotropic factor (CNTF), and oncostatin M (OSM).
      Here, we report the crystallization of the non-glycosylated human-like LIF
      expressed in E. coli. The present crystals diffract to 2.0 A using synchrotron
      radiation. They belong to the monoclinic space group C2, and the cell dimensions
      are a = 61.5 A, b = 45.3 A, c = 77.7 A and beta = 112.3 degrees.

PMID- 8262237
TI  - The vanadium chloroperoxidase from the fungus, Curvularia inaequalis. Evidence
      for the involvement of a histidine residue in the binding of vanadate.
AB  - The binding of vanadate to the novel vanadium chloroperoxidase from C. inaequalis
      was investigated. Reconstitution experiments of apo-chloroperoxidase by vanadate
      at different pH values showed that in the pH 6-7 range an acid/base group is
      present which affects the binding of the vanadate. It is proposed that this group
      is a histidine. This hypothesis was tested by specifically modifying this residue
      using diethylpyrocarbonate. In the apo-enzyme 9 histidines were modified, whereas
      in the holo-enzyme 6 histidines were modified. Modification with
      diethylpyrocarbonate had no effect on the chlorinating activity of the holo
      enzyme, but when the apo-enzyme was modified the reactivation by vanadate was
      strongly inhibited. We conclude that histidine in the active site of
      chloroperoxidase is involved in the binding of vanadate.

PMID- 8262238
TI  - Timing of palmitoylation of influenza virus hemagglutinin.
AB  - The timing of the attachment of fatty acids to the hemagglutinin (HA) of
      influenza A virus was studied. Treatment of virus infected cells with brefeldin A
      (BFA), a drug which blocks intracellular transport along the exocytic pathway at
      a pre-Golgi site, does not prevent palmitoylation of HA. The relationship of HA
      palmitoylation to the oligomerisation and to the proteolytical cleavage of the
      protein revealed that the uncleaved trimer of HA is the substrate for the
      acylating enzyme in virus infected cells. The results are discussed with regard
      to the intracellular site of palmitoylation.

PMID- 8262239
TI  - Chimeric Ca(2+)-ATPase/Na+,K(+)-ATPase molecules. Their phosphoenzyme
      intermediates and sensitivity to Ca2+ and thapsigargin.
AB  - Chimeric molecules consisting of parts from the sarcoplasmic reticulum Ca(2+)
      ATPase and the Na+,K(+)-ATPase were expressed in COS-1 cells and analysed
      functionally. One chimera, in which most of the central cytoplasmic loop was
      derived from the Na+,K(+)-ATPase, while the transmembrane segments and the minor
      cytoplasmic loop came from the Ca(2+)-ATPase, was able to occlude Ca2+ and to be
      phosphorylated from ATP with normal apparent affinity for Ca2+ and ATP. This
      chimera also displayed normal sensitivity to thapsigargin, but was unable to
      undergo the transition from ADP-sensitive to ADP-insensitive phosphoenzyme and to
      transport Ca2+. The other chimera, which consisted of the NH2-terminal two-thirds
      of Na+,K(+)-ATPase and the COOH-terminal one-third of Ca(2+)-ATPase, was unable
      to phosphorylate from ATP, but phosphorylated from inorganic phosphate in a
      Ca(2+)-inhibitable and thapsigargin-insensitive reaction. These results can be
      explained in terms of a structural model in which the non-conserved residues in
      the central cytoplasmic domain of the Ca(2+)-ATPase are without major importance
      for the binding and occlusion of Ca2+, but are involved in the E1P-->E2P
      conformational changes of the phosphoenzyme, whereas residues in transmembrane
      segments on both sides of the central cytoplasmic domain are involved in
      formation of the Ca(2+)-binding sites. The data moreover show that thapsigargin
      sensitivity is dependent on residues in the NH2-terminal one-third of the Ca(2+)
      ATPase molecule.

PMID- 8262240
TI  - Raf-1 is not a major upstream regulator of MAP kinases in rat fibroblasts.
AB  - RCR cells are NRK clones in which Raf-1 production is blocked by the expression
      of an antisense RNA, and consequently they are refractory to transformation by
      various oncogenes. In RCR cells, MAP kinases (ERK1 and ERK2) were activated to an
      extent and in a time course similar to those of the original NRK cells,
      irrespective of whether the stimulus was oncogenic or non-oncogenic. Moreover,
      there was no significant elevation of ERK activities in oncogene-transformed NRK
      cells. These results indicate that Raf-1 kinase is not the major upstream
      activator of ERK's in NRK cells and that neither ERK1 nor ERK2 are likely to
      mediate oncogenic signals from Raf-1 kinase.

PMID- 8262241
TI  - omega-Agatoxin-IVA-sensitive calcium channels in bovine chromaffin cells.
AB  - A large component of the whole-cell currents through Ca2+ channels in bovine
      adrenomedullary chromaffin cells has been shown to be insensitive to both L-type
      and N-type Ca2+ channel blockers, suggesting the existence of a third type of
      Ca2+ channel. In the present paper, omega-agatoxin-IVA (AgTx), a selective
      blocker of P-type Ca2+ channels in mammalian neurons, has been used to
      investigate the presence of this subtype of Ca2+ channel in bovine chromaffin
      cells. Barium currents (IBa) through Ca2+ channels were recorded in whole-cell
      patch-clamped bovine chromaffin cells. IBa was blocked by AgTx in a dose
      dependent and irreversible manner. At the maximal concentration used (1 microM),
      AgTx inhibited IBa by 49.5 +/- 3%. Such a blockade was also present when bovine
      chromaffin cells were pretreated with 10 microM furnidipine, a novel 1,4
      dihydropyridine L-type channel blocker, and after treatment with 1 microM of the
      N-type channel blocker, omega-conotoxin GVIA (CgTx). A combination of these three
      types of Ca2+ channel blockers suppressed the macroscopic Ba2+ currents by 88%.
      We conclude that bovine chromaffin cells, in addition to N- and L-type Ca2+
      channels, possess a P-like component in their whole-cell currents through the
      Ca2+ channels.

PMID- 8262242
TI  - Key active site residues in the inhibition of acetylcholinesterases by soman.
AB  - Molecular modeling (GEMM 7.3) and molecular mechanics calculations (YETI V 5.3)
      using the X-ray coordinates for acetylcholinesterase (AChE) from Torpedo
      californica indicate electrostatic stabilization by the active site, Glu-199, of
      the developing positive charge on the incipient carbonium ion in the dealkylation
      in the adducts of AChE with PSCR and PSCS diastereomers of 2-(3,3-dimethylbutyl)
      methylphosphonofluoridate (soman). His-440 is indispensable as a general acid
      catalyst of C-O bond breaking in the dealkylation reaction and that of bond
      breaking to the Ser gamma-O in reactivation. This demand for catalysis seems to
      be satisfied for the reactivation of enzyme from the PSCS diastereomer of soman,
      but not from the P(S)C(R) diastereomer.

PMID- 8262243
TI  - Myo-inositol 1,3,4,5-tetrakisphosphate can independently mobilise intracellular
      calcium, via the inositol 1,4,5-trisphosphate receptor: studies with myo-inositol
      1,4,5-trisphosphate-3-phosphorothioate and myo-inositol hexakisphosphate.
AB  - Myo-inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] acts as a full agonist
      for Ca2+ release in saponin-permeabilised SH-SY5Y neuroblastoma cells. Studies
      were conducted in the presence of myo-inositol hexakisphosphate (InsP6, 10
      microM), to inhibit the Ins(1,3,4,5)P(4)-3-phosphatase catalysed back conversion
      of Ins(1,3,4,5)P4 to Ins(1,4,5)P3. HPLC analysis confirmed that Ins(1,3,4,5)P4
      releases the entire content of Ins(1,4,5)P3-sensitive intracellular Ca2+ stores,
      independent of 3-phosphatase activity. Further we utilised racemic myo-inositol
      1,4,5-trisphosphate-3-phosphorothioate [DL-Ins(1,3,4,5)P(4)-3S], a novel
      intrinsically Ins(1,3,4,5)P(4)-3-phosphatase resistant Ins(1,3,4,5)P4 analogue.
      DL-Ins(1,3,4,5)P(4)-3S specifically displaced [3H]Ins(1,4,5)P3 from bovine
      adrenal cortex Ins(1,4,5)P3 binding sites (IC50 = 889 nM, compared to
      Ins(1,4,5)P3, IC50 = 4.4 nM and Ins(1,3,4,5)P4, IC50 = 152 nM). DL
      Ins(1,3,4,5)P(4)-3S was a full agonist for Ca2+ release (EC50 = 4.7 microM),
      being 90- and 2-fold less potent than Ins(1,4,5)P3 and Ins(1,3,4,5)P4 (with
      InsP6), respectively. DL-Ins(1,3,4,5)P(4)-3S will be an important tool for
      identification of potentially exclusive Ins(1,3,4,5)P4 second messenger
      functions, since its resistance to 3-phosphatase action precludes the
      inconvenient artefact of steady state Ins(1,4,5)P3 generation.

PMID- 8262244
TI  - Retinal oxidase is identical to aldehyde oxidase.
AB  - Retinal oxidase (EC 1.2.3.11) and aldehyde oxidase (EC 1.2.3.1) were compared
      with respect to their enzymatic and physiochemical properties. It was found that
      the molecular weights, subunits, optical spectra, chemical and immunological
      properties, cellular localization and substrate specificities of the two oxidases
      are identical on almost all points. The physiological function of aldehyde
      oxidase appears to be the synthesis of retinoic acid from retinal.

PMID- 8262245
TI  - Production of the Alzheimer's beta-amyloid peptide by C6 glioma cells.
AB  - The beta-amyloid peptide (A beta) is a 4 kDa proteolytic fragment derived from
      the beta-amyloid precursor protein (beta APP) which is deposited as amyloid
      fibrils in the brains of patients with Alzheimer's disease. beta APP processing
      was investigated in C6 glioma cells using several affinity-purified anti-peptide
      antibodies raised against different domains of the protein. Both direct
      immunoblot analysis of C6 glioma conditioned medium and metabolic labeling of
      cells followed by immunoprecipitation of extracellular medium with specific
      antibodies revealed that these glial cells normally produce and release a soluble
      4 kDa peptide which co-migrates with synthetic A beta (1-40) and is specifically
      recognized by antibodies raised against N- or C-terminal domains of the beta
      amyloid peptide. Our results further suggest that glial cells may prove a major
      source of beta-amyloid production in the nervous tissue.

PMID- 8262246
TI  - Demonstration of (Ca(2+)-Mg2+)-ATPase activity of the neural cell adhesion
      molecule.
AB  - In this study a possible association between (Ca(2+)-Mg2+)-ATPase activity and
      the neural cell adhesion molecule, NCAM, was investigated. The effects of various
      detergents on ATPase activity were evaluated, and it was found that
      solubilization of rat brain microsomes with 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate, CHAPS, released a major
      fraction of the (Ca(2+)-Mg2+)-ATPase activity together with NCAM. Using different
      types of solid phase immunoadsorption it was shown that NCAM antibodies
      selectively isolated ATPase activity. Furthermore, agarose gel
      immunoelectrophoresis of solubilized brain microsomes followed by ATPase assay
      directly in the gel revealed ATPase activity associated with the NCAM
      immunoprecipitate. The NCAM-associated enzyme activity had a broad nucleoside
      triphosphate specificity and no strict selectivity for divalent cations,
      indicating that the enzyme probably is an ecto-ATPase. This raises a series of
      intriguing questions in relation to NCAM adhesive functions.

PMID- 8262247
TI  - Molecular cloning of a putative homolog of proline/arginine-rich antibacterial
      peptides from porcine bone marrow.
AB  - Screening of a porcine bone marrow cDNA library with a PCR-derived probe from
      rabbit LPS-binding protein CAP18 led to the discovery of two closely related
      clones. The longer, full-length cDNA clone encodes a 228 amino acid residue
      protein similar to the family of antibacterial/LPS-binding cationic peptides. In
      contrast to other hitherto discovered precursors of Pro/Arg-rich peptides from
      this family, they have a novel, unique structure of the C-terminal region of 100
      amino acid residues with a repeating sequence of ten residues (FPPPNXPGPR, where
      X = V or F). These precursors could represent a part of the antibacterial peptide
      repertoire of porcine bone marrow.

PMID- 8262248
TI  - Pig leukocyte cysteine proteinase inhibitor (PLCPI), a new member of the stefin
      family.
AB  - A new stefin type low-M(r) cysteine proteinase inhibitor (PLCPI) was isolated
      from pig polymorphonuclear leukocytes as a contaminant of the cathelin sample.
      The inhibitor consists of 103 amino acids, and its M(r) was calculated to be
      11,768. The inhibitor exhibits considerable sequence identity with inhibitors
      from the stefin family, particularly with human stefin A. The PLCPI is a fast
      acting inhibitor of papain and cathepsins L and S (k(ass) > or = 1 x 10(6) M-1 x
      s-1) and forms very tight complexes with these enzymes (Ki < or = 190 pM). The
      affinity for cathepsins B and H (Ki > or = 125 nM) was lower. These results also
      show that the inhibitory activity previously ascribed to cathelin was due to the
      presence of PLCPI.

PMID- 8262249
TI  - Different flexibility of the upstream regulatory regions of two differently
      expressed pea rbcS genes studied by theoretical evaluation of DNA distortion
      energy and cyclization kinetics.
AB  - Different superstructural features of the upstream regulatory regions of the two
      pea genes rbcS-3A and rbcS-E9 have been derived using a theoretical method,
      developed in our laboratory a few years ago, which evaluates the DNA distortion
      energy from a matrix of the deviations of the 16 possible dinucleotides from the
      standard B conformation. The theoretical analysis, which predicts different
      flexibilities of the regulatory regions of the two genes, is in satisfactorily
      good agreement with experimental evaluations from gel electrophoretic mobility
      and cyclization kinetics, suggesting a possible model to explain the largely
      different transcription efficiencies of the two genes.

PMID- 8262250
TI  - Analysis of lactase processing in rabbit.
AB  - The proteolytic processing of rabbit intestinal lactase-phlorizin-hydrolase (LPH)
      was studied by pulse-chase and continuous labeling experiments in organ culture
      from 15-day-old rabbits in the presence of glycosylation and processing
      inhibitors. Monensin and brefeldin A inhibited the two proteolytic cleavages of
      the precursor indicating that they are post-Golgi events as previously reported
      for the unique cleavage of LPH in man. The inhibition was not related to a
      concomitant alteration glycosylation; in fact, if trimming was blocked by MDNM
      the abnormal glycosylated precursor was proteolytically processed normally.
      Finally the use of the anti-microtubular drug colchicine strongly inhibited both
      cleavages and caused accumulation of the complex-glycosylated precursor form the
      brush border fraction indicating that proteolytic events depend on intact
      microtubule (transport).

PMID- 8262251
TI  - Chloride-depletion of photosynthetic water oxidase. No proton release during the
      second oxidation step, S2*==>S3*, and a transmembrane radical pair recombination
      from the third on.
AB  - Chloride depletion blocks the normal four-step progress of photosynthetic water
      oxidation. We studied proton release in chloride-depleted thylakoids which were
      dark-adapted and excited by flashing light. Proton release was blocked from the
      second flash on, possibly leaving an uncompensated positive charge in the
      catalytic centre. The reduction of P+680 by Tyrz was still very rapid (<< 10
      microseconds). From the third flash on, P+680 was reduced more slowly (70
      microseconds/200 microseconds), and by an electrogenic back-reaction. The
      uncompensated positive charge may be the reason why the rapid reduction of P+680
      by Tyrz is prevented and the transmembrane charge-pair recombination is
      facilitated.

PMID- 8262252
TI  - Human ferritin H-chains can be obtained in non-assembled stable forms which have
      ferroxidase activity.
AB  - We found conditions to obtain the Leu-169-->Arg mutant of human ferritin H chain
      in a stable and non-assembled state. The protein obtained is an oligomer of
      subunits with a high degree of structured conformation, and when concentrated it
      re-assembles into ferritin cages. Functional studies showed that (i) it promotes
      iron oxidation like the assembled ferritin, but at slower rate, (ii) it is
      readily precipitated by the oxidised iron unless apotransferrin or L-chain
      ferritin are added to sequester Fe(III). The results confirm that ferroxidase
      activity is located within the H-chain, and indicate that the cages of the fully
      assembled ferritins are important not only in maintaining iron in a soluble form,
      but also in eliciting the activity of the ferroxidase centres.

PMID- 8262253
TI  - Molecular cloning of a novel putative G protein-coupled receptor (GPCR21) which
      is expressed predominantly in mouse central nervous system.
AB  - A novel cDNA clone encoding a putative G protein-coupled receptor (named GPCR21)
      was isolated from a mouse brain cDNA library along with its homologue, GPCR01
      (the mouse counterpart of previously reported rat receptor R334 [(1991) FEBS
      Lett. 292, 243-248]) by the polymerase chain reaction using degenerate
      oligonucleotide primers. Northern blotting and reverse transcription-polymerase
      chain reaction analyses showed predominant expression of these two receptors in
      the central nervous system. In situ hybridization analysis revealed their
      prominent expression in the limbic system and further demonstrated the
      differential distribution of their mRNAs in mouse brain. Although the ligands for
      these receptors are yet to be identified, the significant sequence homology
      between these receptors suggests that they constitute a new receptor subfamily
      and they possibly represent different receptor subtypes for an unknown
      neurotransmitter.

PMID- 8262254
TI  - The role of calcium in the organization of fibrillin microfibrils.
AB  - The microfibrillar glycoprotein fibrillin has a multidomain structure which
      contains forty-three epidermal growth factor-like motifs with calcium-binding
      consensus sequences. We have utilized intact microfibrils isolated from human
      dermal fibroblast cultures to investigate the putative influence of bound calcium
      on microfibrillar organization and integrity. Incubation with EDTA or EGTA
      rapidly resulted in gross disruption of microfibril morphology. The treatment
      induced disorganization of the interbead domains although the regular beaded
      arrangement was always apparent. These changes were readily reversible on
      replacing calcium, indicating that the treatment had not compromised
      microfibrillar integrity. The data localize calcium binding EGF-like repeats to
      the interbead domains and indicate that lateral packing of fibrillin monomers is
      calcium-dependent. This arrangement suggests how mutations in epidermal growth
      factor-like domains of fibrillin might cause the disruption in microfibril
      organization and interactions which underlies the clinical symptoms of some
      Marfan syndrome patients.

PMID- 8262255
TI  - Degradation of human apolipoprotein B-100 by apolipoprotein(a).
AB  - Human plasma low density lipoproteins (LDL) contain a very high molecular weight
      protein termed apoB-100 (M(r) = 550,000). In many samples of LDL, minor
      components designated as apoB-74 (M(r) = 407,000) and apoB-26 (M(r) = 145,000)
      are present. It has been shown that they can arise as a result of proteolytic
      degradation of apoB-100. Our earlier studies demonstrated that the active forms
      of lipoprotein(a) (LP(a)) and apolipoprotein(a) (apo(a)) possess proteolytic
      activity. In the present study we investigated the possibility of apoB-100
      degradation in the presence of activated apo(a). LDL were incubated with the
      purified apo(a) and analyzed by SDS-polyacrylamide gel electrophoresis. It was
      found that apoB is cleaved by apo(a) with formation of proteolytic fragments
      including B-74 and B-26. The physiological significance of apoB degradation under
      the action of apo(a) is considered.

PMID- 8262256
TI  - PsaL subunit is required for the formation of photosystem I trimers in the
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - When membranes of the wild type strain of the cyanobacterium Synechocystis sp.
      PCC 6803 were solubilized with detergents and fractionated by sucrose-gradient
      ultracentrifugation, photosystem I could be obtained as trimers and monomers. We
      could not obtain trimers from the membranes of any mutant strain that lacked PsaL
      subunit. In contrast, absence of PsaE, PsaD, PsaF, or PsaJ did not completely
      abolish the ability of photosystem I to form trimers. Furthermore, PsaL is
      accessible to digestion by thermolysin in the monomers but not in the trimers of
      photosystem I purified from wild type membranes. Therefore, PsaL is necessary for
      trimerization of photosystem I and may constitute the trimer-forming domain in
      the structure of photosystem I.

PMID- 8262257
TI  - Down-modulation of CD4 antigen during programmed cell death in U937 cells.
AB  - It has been hypothesized that programmed cell death (PCD), an active cell suicide
      process occurring in place of necrosis, can be associated with the pathogenesis
      of acquired immunodeficiency syndrome (AIDS). The entry of human immunodeficiency
      virus (HIV) into competent cells is mediated by the CD4 molecule present on the
      surface of certain lymphocyte subpopulations as well as on some cultured cell
      lines, e.g. U937 myelomonocytic cells. The present paper focuses on some specific
      aspects of PCD induced by the cytokine tumor necrosis factor (TNF). The results
      obtained indicate that the exposure of U937 cells to cycloheximide facilitates
      TNF-mediated PCD via a short term cell death program and modifies the expression
      of CD4 surface molecules. This change in surface antigen expression, manifested
      by internalization of the CD4 molecule, occurs in cells in which apoptosis has
      been triggered, but not in cells undergoing necrosis. These results indicate that
      the progression of cell death could be associated with specific alterations of
      certain surface molecules and could have a role in the entry of HIV into cells.

PMID- 8262258
TI  - Identification of DNA binding proteins in vaccinia virus by DNA-protein
      crosslinking.
AB  - DNA binding proteins of vaccinia virus (VV) virions, strain LIVP, have been
      studied by their covalent crosslinking to DNA, using two-dimensional gel
      retardation electrophoresis of crosslinked DNA and proteins as well as the
      'protein image' hybridization assay. Five proteins with molecular masses of 16,
      25, 27, 41 and 54 kDa, respectively, associated with all analysed DNA sequences,
      including early and late genes and their promoters, have been identified.

PMID- 8262259
TI  - Percoll purification of chromaffin granules inhibits their ability to take up and
      maintain calcium.
AB  - Secretory granules of the adrenal medulla have recently been shown to be able to
      sequester and release Ca2+, in addition to their previously established role as
      carriers of secretory products. In order to study the ability of these or any
      other secretory granules to participate in intracellular calcium homeostasis, it
      is imperative that they should be free of other contaminating Ca2+ sequestering
      organelles, and that the Ca2+ uptake and release mechanisms of those granules
      should remain intact throughout any chosen purification procedure. We report here
      that chromaffin granules which were purified by the isopycnic gradient medium
      Percoll, or even incubated with it, showed an attenuated ability to sequester
      Ca2+.

PMID- 8262260
TI  - The outer membrane of plant mitochondria contains a calcium-dependent protein
      kinase and multiple phosphoproteins.
AB  - Highly purified mitochondria from potato (Solanum tuberosum L. cv. Bintje) tubers
      were subfractionated into a matrix fraction, an inner membrane fraction and an
      outer membrane fraction with minimal cross-contamination. When the matrix and
      inner membrane fractions were incubated with [gamma-32P]ATP only one and three
      prominent phosphoproteins were detected after SDS-PAGE and autoradiography,
      respectively. In contrast, more than 20 phosphoproteins could be labelled in the
      outer membrane fraction, the main ones at 12, 18, 26, 43, 58, 60, 65, 74 and 110
      kDa. Only one band, at 18 kDa, was detectable when the labelling was done in the
      presence of EGTA. We conclude that the outer membrane of plant mitochondria
      contains at least one Ca(2+)-dependent protein kinase and more than 20 endogenous
      substrates.

PMID- 8262261
TI  - Participation of the g = 1.9 and g = 1.82 EPR forms of the semiquinone-iron
      complex, QA-.Fe2+ of photosystem II in the generation of the Q and C
      thermoluminescence bands, respectively.
AB  - Following illumination at 200 K, the charge recombination reactions and the
      origin of the thermoluminescence (TL) bands appearing at about 0 degree C (Q
      band) and +50 degrees C (C band) in the glow curve were investigated by
      comparative TL and EPR measurements in DCMU-treated photosystem II particles.
      Decay half-time measurements carried out at -25 degrees C and +25 degrees C,
      respectively, suggest that the S2 state (multi-line signal) undergoes charge
      recombination with the g = 1.9 form of the semiquinone-iron complex, QA-.Fe2+,
      resulting in the appearance of the Q band, and that the g = 1.82 form of QA-.Fe2+
      back-reacts with the oxidized tyrosine, YD+ (Signal IIs), accounting for the
      generation of the C band.

PMID- 8262262
TI  - Similarity of primary radical pair recombination in photosystem II and bacterial
      reaction centers.
AB  - We report temperature and magnetic field dependent measurements of the
      recombination dynamics of the radical pair P680+Pheo- in D1D2cytb559 reaction
      centers of photosystem II and compare the results to those obtained in bacterial
      reaction centers. In photosystem II the rate of recombination to the groundstate
      is found to be slower than in the bacterial reaction centers by a factor of at
      least 50. This difference arises from the different redox potentials of the
      pigments of plant and bacterial reaction centers. In contrast, the rate of
      recombination to the triplet state is similar in all reaction centers, indicating
      a similar electronic coupling which allows us to conclude upon the structural
      similarity.

PMID- 8262263
TI  - The structure of apo-calmodulin. A 1H NMR examination of the carboxy-terminal
      domain.
AB  - The structure of the carboxy-terminal domain of bovine calmodulin, TR2C, in the
      calcium-free form was investigated using two-dimensional 1H NMR. Sequential
      resonance assignments were made using standard methods. Using information from
      medium and long range contacts revealed by nuclear Overhauser enhancement, the
      secondary structure and global fold were determined. The apo protein possesses
      essentially the same secondary structure as that in the calcium activated form of
      intact calmodulin. However, the secondary structural elements are rearranged so
      that the hydrophobic binding pocket is closed in the apo-form.

PMID- 8262264
TI  - Molecular basis for sperm-oocyte interaction.

PMID- 8262265
TI  - Adrenergic innervation of the epididymis, vas deferens, accessory genital glands
      and urethra in the boar.
AB  - The distribution of adrenergic nerve fibres in the urethra and some organs of the
      male reproductive system of juvenile boars was studied by applying the glioxylic
      acid-induced fluorescence method. Adrenergic nerve fibres were found in all
      structures examined, with particular relation to their muscular coats and
      arterial blood vessels. Ductuli efferentes and ductus epididymidis from the caput
      region were weakly innervated. The number of adrenergic nerve fibres innervating
      the ductus epididymidis gradually increased towards the cauda epididymidis, being
      greatest in this region. The vas deferens was very well supplied with these
      nerves. The seminal vesicle was found to be the richest innervated organ in
      comparison with other accessory genital glands. The body of the prostate was
      slightly weaker innervated, while the disseminated part of the prostate as well
      as the bulbourethral gland comprised the smallest number of adrenergic nerve
      fibres. The urethra received a very dense adrenergic nerve supply. The pelvic
      part of the urogenital duct possessed a moderate number of adrenergic nerves,
      which supplied not only the muscular membrane but also venous sinuses of the
      mucosa. In a close vicinity to the internal genital organs numerous ganglia
      containing both adrenergic and non-adrenergic nerve cell bodies were observed.
      The presented data suggest that adrenergic innervation may be deeply involved in
      the control of blood flow and motor function of the organs studied, and that a
      part of adrenergic nerve fibers innervating these structures may originate from
      pelvic ganglia.

PMID- 8262266
TI  - Characterization of the crude membrane fraction of cardiomyocytes using enzyme
      cytochemical markers.
AB  - The crude membrane fraction of cardiomyocytes, which had been used as the antigen
      for the study of autoantibodies against beta-adrenergic receptors, was
      characterized using cytochemical methods: in a reaction for adenylate cyclase as
      an enzyme marker of the beta-receptors of plasma membrane and in a reaction for
      glucose-6-phosphatase as an enzyme marker of the sarcoplasmic reticulum. The
      specific precipitates of both enzyme reactions were localized on the membrane
      vesicles. In case of AC reaction the precipitate was observed on approximately
      80% and in case of G-6-Pase on approximately 25% of the whole amount of the
      vesicles observed, indicating prevalence of vesicles of plasmalemmal origin.
      These results reveal that the used membrane fraction is appropriate for the study
      of autoantibodies against beta-receptors, but it can also contain other proteins
      (antigens) which can cross-react with autoantibodies against beta-adrenergic
      receptors.

PMID- 8262267
TI  - Effects of hydrocortisone on the lymphoid organs of Rana temporaria.
AB  - In vivo and in vitro effects of hydrocortisone hemisuccinate (HC) on the lymphoid
      organs were studied in the European common frog Rana temporaria. Single HC
      injection at the dose of 0.5 mg/g body weight induced rapid but fully reversible
      changes in thymuses and jugular bodies while its effect on spleens was
      negligible. In vitro studies confirmed HC-sensitivity of thymuses and jugular
      bodies and relative HC-resistance of spleens of this species. In vitro exposition
      of thymic and jugular body cell suspensions to 0.25-1.00 mg/ml HC solution
      revealed a dose-dependent and time-dependent impairment of sample activities
      associated with massive cell death as judged by MTT reduction assay and Trypan
      blue uptake, respectively. Evolutionary implications of these results are
      discussed.

PMID- 8262268
TI  - Lectin binding to olfactory system in a shark, Scyliorhinus canicula.
AB  - Lectin histochemical studies were performed on the olfactory system of
      Scyliorhinus canicula to identify specific glycoconjugates on the cell surface of
      primary olfactory neurons. The olfactory receptor cells, the olfactory nerve
      fibers and their terminals in the bulbs were labelled with SBA, BSA-I and BSA-I
      B4. The lectin staining patterns indicate that the membranes of small-spotted
      catshark olfactory neurons had glycoproteins with alpha-galactose residues. This
      carbohydrate moiety could be related to modulation of the cell-cell interactions
      in the olfactory system.

PMID- 8262269
TI  - The lipoprotein crystals in yolk platelets of a shark, Squalus ocanthias
      (Selachii).
AB  - Lipovitellin-phosvitin crystals in yolk platelets from the egg of a shark,
      Squalus ocanthias (Selachii), were studied by the selected area electron
      diffraction method. Ultra-thin sections of yolk platelets possess an orthorhombic
      lattice with lattice parameters: a = 8.0 nm, b = 15.9 nm, and c = 18.1 nm.
      Comparative and quality analysis of the reflection intensities of electron
      diffraction patterns between shark and other vertebrate yolk platelets suggest
      evolutionary variability of the lipovitellin structure. The lattice and its
      parameters, however, are highly conserved. The results of the present study fill
      the last gap in the comparative yolk platelet research which has been carried out
      over many years for exponents of all vertebrate taxonomic groups, from
      cyclostomes to reptiles.

PMID- 8262270
TI  - Localization of calcium-dependent ATPase in germinating pollen grain and pollen
      tube in Vicia faba.
AB  - It was demonstrated by a cytochemical method that the calcium-dependent ATPase
      was present in the germinating pollen grain. Immediately after hydration the
      enzyme was observed in the pollen plasmalemma. During germination, the chief
      sites of the enzyme activity were the plasmalemma around the aperture site and
      the cisternae of endoplasmic reticulum. In the pollen grain with a grown tube,
      the enzyme was localized in the plasmalemma of the tube tip, in the endoplasmic
      reticulum below the tip, and in the tonoplast of the vacuoles formed in the
      pollen grain after tube germination.

PMID- 8262271
TI  - [A case of acute suppurative thyroiditis associated with thyroid papillary
      carcinoma].
AB  - A sixty-one-year-old female was admitted to our hospital in October 1988 because
      of fever and a right neck mass associated with redness and tenderness. The size
      of the thyroid mass had gradually increased over 3 months. Two masses were
      detected in the thyroid by ultrasonography and MRI. She has positive thyroid
      autoantibodies, high CRP levels and high erythrocyte sedimentation rates. While
      she had normal white blood cell counts, massive neutrophils were obtained from
      her thyroid mass by aspiration biopsy, indicating acute suppurative thyroiditis.
      However, we could not find any bacteria to cause suppurative thyroiditis either
      in the blood or in thyroid aspirates. Serum levels of thyroid hormone were
      slightly elevated but she did not complain of any thyrotoxic symptoms.
      Radioactive iodine uptake (RAIU) of the thyroid gland was markedly decreased
      (2%/24h). Following treatment with antibiotics, her inflammation and symptoms
      immediately improved, and pus spontaneously ran from the collapsed thyroid mass.
      Then serum thyroid hormone levels and RAIU were normalized and the right thyroid
      mass disappeared. She was discharged in December 1988. There were no signs of
      recurrence of suppurative thyroiditis until now. She received a pharyngo
      esophageal barium examination in search of the route of infection 4 times, but no
      fistula was revealed. However, as her left thyroid mass consistently remained
      thereafter, an operation of the left thyroid mass was performed in December 1989.
      The histologic examination of the resected thyroid revealed the coexistence of
      encapsulated follicular adenoma, minute papillary carcinoma and chronic
      thyroiditis. There are few reports of such a case having a combination of
      suppurative thyroiditis, thyroid cancer and chronic thyroiditis observed in an
      elderly female.

PMID- 8262272
TI  - [A study with diagnostic standard of occult hyperprolactinemia (OHP) and the
      effect of bromocriptine administration].
AB  - It is well known that the transient excessive increase of serum prolactin level
      is harmful for the mechanism of ovulation or the steroidogenesis of the ovaries.
      The pathogenesis of latent or occult hyperprolactinemia (OHP) has been
      investigated recently. The present study was conducted to determine the
      diagnostic standard of OHP, and to elucidate the efficacy of bromocriptine
      administration for the treatment of OHP and other ovulatory disturbances. 110
      cases of hypothalamic anovulations were selected from 385 cases of infertile
      patients by the LH-RH and TRH loading tests. Bromocriptine (5mg/day) was
      administered to all of the subjects for more than three months, and the efficacy
      of the bromocriptine administration was investigated. Follicular development was
      observed by transvaginal ultrasonography (mature follicular diameters > or =
      20mm), and also luteal function was estimated by the duration of the luteal phase
      in the BBT charts (high phase > or = 12 days), the mid-luteal serum estradiol (>
      or = 200pg/ml) and progesterone (> or = 10ng/ml) levels. The subjects were
      divided into two groups: group A, bromocriptine effective patients (63 cases) and
      group B, bromocriptine non effective patients (47 cases). The results of the LH
      RH and TRH loading tests were compared between these two groups. Serum prolactin
      levels at 30 min. after TRH loading (PRL30) in group B (61.5 +/- 28.3 vs. 38.0 +/
      19.3ng/ml, p < 0.01). At the cut-off points of 50, 60 and 70ng/ml over in the
      values of the PRL, the efficacies of the bromocriptine administration were 77.4,
      78.9 and 88.5%, respectively. From these facts, it was thought suitable that the
      diagnostic standard of OHP was PRL30 > or = 70ng/ml, and values of PRL30 from 50
      to 70ng/ml were borderline cases of OHP. The efficacy of the bromocriptine
      administration in the cases without OHP (n = 57) was also investigated. Serum LH
      levels at 30 min. after LH-RH loading (LH30) were compared between the cases of
      the bromocriptine effective (n = 22) and non effective (n = 35). As a result, the
      LH30 of the former was significantly higher than that of the latter (96.5 +/-
      64.2 vs. 45.1 +/- 31.5mIU/ml, p < 0.005). In conclusion, the diagnostic standard
      of OHP was determined as PRL30 > or = 70ng/ml (borderline: 50 > 70ng/ml), and
      bromocriptine administration was effective not only in cases of OHP, but also in
      cases of hyperreactivities of LH (so-called endocrinological PCOD).

PMID- 8262273
TI  - [Dopamine and hypertension].
AB  - Dopamine has been well recognized to be a precursor of norepinephrine, exhibiting
      cardiovascular effects through alpha-adrenoceptor stimulation by norepinephrine
      production and release in sympathetic nerve endings. It also has the specific and
      unique effects of natriuresis and vasodilation. Since dopamine is one of the
      important endogenous hypotensive and natriuretic substances, it is speculated
      that impaired dopamine generation and/or the disturbance of the effects of
      dopamine could cause hypertension with suppression of plasma renin activity
      and/or salt-sensitivity. A non-specific enzyme of aromatic L-amine acid
      decarboxylase (AAAD) converting from 3,4-dihydroxyphenylalanine (DOPA) to
      dopamine is widely distributed in the peripheral tissue, e.g. the sympatho
      adrenomedullary system, the small intestine, the lung, the liver, the kidney,
      etc. Since tyrosine hydroxylase is a rate-limiting enzyme of catecholamine
      biosynthesis, DOPA generation in the neuronal tissues is accelerated with the
      sympathetic nerve activation by stress such as emotional and environmental
      changes, resulting in an increase of DOPA delivery to the non-neuronal tissues
      containing non-neuronal AAAD. More than five receptors for dopamine are cloned in
      the brain, and it is suggested that more than three different types of dopamine
      receptors are in the peripheral tissues. In spontaneously hypertensive rats, the
      post-receptor defect of renal dopamine D1-receptor has been proposed where
      peripheral dopamine generation compensatorily increased. In Dahl salt-sensitive
      rats, another model of genetic hypertension, the blunted response of urinary
      dopamine to sodium loading has been demonstrated. It is controversial whether
      abnormalities of the neuronal and/or non-neuronal (particularly renal) dopamine
      system play a contributory role on the pathogenesis of essential hypertension.
      However, it is plausible that the impairment of dopamine generation and/or the
      defective responses of a dopamine receptor might induce sodium retention and
      hypertension.

PMID- 8262274
TI  - [Cellular biology of sex steroid and clinical implication].
AB  - Advances in molecular biology contribute to additional precise knowledge of sex
      steroid biology. Sex steroids, estrogens, androgens, and progesterone can exert
      their characteristic biological effects via cellular mechanism on their targets.
      Sex steroids are derived from the gonads and interact with SHBG or CBG, which is
      located in the serum, on the plasma-membrane and in the cytoplasm. They exert
      their known biological effects via interaction with cellular components such as
      the plasma membrane, the cytoplasmic component, the nuclear receptor, and the
      nuclear matrix. Estrogens and androgens are detected in the serum of both sexes,
      which shows the necessity of both steroids for the expression of either sex
      characteristics. Sex steroids and their metabolites can demonstrate individually
      different biological effects, suggesting the presence of the individual
      receptors. The presence of cooperative effects among each steroid induces
      complexity in the evaluation of each steroid effect. As to the imbalance of the
      effects of sex steroids, the predominance of estrogens induces female dimorphism
      of autoimmune diseases and the protective effects on psychoneurological diseases,
      and that of androgens does the reverse. The continuous exposure to estrogens (and
      androgens) may induce benign and malignant tumors in their target organs. Various
      mutations mainly in sex steroid receptor genes, and other unknown abnormalities
      cause sex steroid resistance, e.g. male pseudohermaphroditism and uterine
      dysfunction. Finally, climacteric disorders are derived from estrogen-deficiency
      and can be managed by estrogens under the milieu of an expanded lifespan.

PMID- 8262275
TI  - [Studies of WBN/Kob rat, 18th report: effect of 1 alpha-OH-D3 on diabetic
      osteopenia].
AB  - We examined the effect of 1 alpha-OH-D3 on diabetic osteopenia in spontaneously
      developed diabetic WBN/Kob rats. Diabetic male WBN/Kob rats aged 12 to 15 months
      were randomly divided into 1 alpha-OH-D3-treated group (n = 6) and control group
      (n = 5). 1 alpha-OH-D3 was administered 3 times a week at an oral dose of 0.1
      microgram/kg and triglyceride was administered in the control group during the
      observation period of 12 weeks. Although plasma Ca level decreased significantly
      in the vehicle-treated group, there was no significant change in plasma Ca level
      in the 1 alpha-OH-D3-treated group. Urinary Ca excretion significantly increased
      in the 1 alpha-OH-D3-treated group compared with that in the vehicle-treated
      group. As for plasma vitamin D metabolites levels after the 12 week-treatment,
      although there was no significant difference in plasma 25-OH-D and 24,25(OH)2D
      levels, plasma 1,25(OH)2D level was significantly increased in the 1 alpha-OH-D3
      treated group compared with that in the vehicle-treated group. There was no
      significant difference in plasma bone-Gla protein level between 1 alpha-OH-D3
      treated and vehicle-treated groups. As for bone mineral content (BMC) in the
      femur measured by a dual energy absorptiometer, BMC was significantly increased
      in the 1 alpha-OH-D3-treated group compared with than in the vehicle-treated
      group. In conclusion, 1 alpha-OH-D3 ameliorated diabetic osteopenia in WBN/Kob
      rats through the normalization of vitamin D metabolism.

PMID- 8262276
TI  - Fertility and family planning among the elderly in Taiwan, or integrating the
      demography of aging into population studies.

PMID- 8262277
TI  - How Demography was born.

PMID- 8262278
TI  - Thirty years of Demography.
AB  - In this paper, we present a content analysis of Demography, the official journal
      of the Population Association of America. Our results reflect patterns of change
      and stability in a number of areas, including: subjects covered, number of
      authors, gender of authors, type of data used, source of data used, affiliation
      of authors and statistical procedures employed. The data suggest that the field
      of population research has become increasingly bureaucratized and complex, while
      at the same time continuing to focus on familiar research subjects. A relatively
      small number of population research centers contribute disproportionately to the
      journal.

PMID- 8262279
TI  - Thirty years of demography and Demography.

PMID- 8262280
TI  - If all we knew about women was what we read in Demography, what would we know?

PMID- 8262281
TI  - Demography: the past 30 years, the present, and the future.
AB  - In a population, 30 years approximates the mean length of a generation or the
      time in which one generation replaces the previous one. In most areas of
      demographic research, one generation of research replaces the next in a
      considerably shorter period. A glance at what demographers were doing 30 years
      ago shows that in most areas, past research no more resembles what demographers
      do now than the Friedan calculators of that period resemble our current desktop
      computing environments. In these areas, current research differs from the
      research of 30 years ago in the theoretical approach, in the methods employed,
      and in the type of data used. Where great change has occurred, theory, methods,
      and data appear to have evolved together: each has changed in response to changes
      in the other areas and then has demanded further developments in those areas.
      Formal demography is one area that has been characterized by continuity. The
      questions addressed and the basic techniques employed build on a long heritage,
      even while steady progress is made in the development of methodology and analytic
      techniques. Analysis of the 1980s reintroduced the idea of context--the idea that
      behavior is influenced not only by the characteristics of individuals but also of
      the environment in which the behavior takes place. In the 1990s, this approach
      will be incorporated more thoroughly into theoretical developments in all areas
      of demography as we attempt increasingly to make comparisons across cohorts and
      time while continuing to model individual behavior. Mortality is the
      theoretically underdeveloped area of demography which probably will show the
      greatest change in the next 30 years.

PMID- 8262282
TI  - The contours of demography: estimates and projections.
AB  - This paper considers the scope of demography and the various research approaches
      that legitimately could claim the label. As a small field lacking security in
      academic structures, demography has been unusually sensitive to demand factors,
      including those associated with perceived population problems. International
      health is cited as an area of increased demographic presence; reasons for this
      development are explored. The technology for performing research in demography is
      improving more rapidly than in many other areas of the social sciences, and thus
      is helping to improve the relative standing of the field. Taking a demand
      oriented approach, the paper identifies several promising research areas in which
      demographers will be called on to address issues of national and international
      concern.

PMID- 8262283
TI  - The link between population density and welfare participation.
AB  - This article explores a neglected topic in the social welfare, poverty, and
      demographic literatures--the link between population density and welfare
      participation in the United States. Longitudinal data from the Panel Study of
      Income Dynamics are used to meet two objectives: first, to test whether a
      relationship exists between population density and use of the food stamp program
      among eligible households; second, to explore the potential reasons for such a
      relationship. Our findings show that population density has a strong, positive
      impact on the likelihood of participating in the food stamp program. Low-income
      respondents in urban areas are significantly more likely to use food stamps in
      both an aggregate and a multivariate context. In analyzing the dynamic underlying
      such an effect, we find that those in urban areas are more likely to possess
      accurate eligibility information and to hold less adverse attitudes toward the
      use of welfare. These factors in turn increase the likelihood of food stamp
      participation.

PMID- 8262284
TI  - The human ecology of tornadoes.
AB  - This paper offers an empirical test of the impact of human ecological patterns
      and other known correlates on tornado occurrence. It uses the National Severe
      Storms Forecast Center's information on tornadoes from 1950 through 1990 and
      employs ecological data from the U.S. Bureau of the Census and the Environmental
      Protection Agency. The results show that metropolitan and other urban counties
      have higher odds of tornado occurrence than rural counties, and that the
      probability of occurrence of tornadoes increases with increases in the number of
      previous tornadoes. The paper assesses the meaning of this finding for
      demographers, atmospheric scientists, engineers, and disaster managers.

PMID- 8262285
TI  - Changing identification among American Indians and Alaska Natives.
AB  - The census-enumerated American Indian population dispersed rapidly between 1930
      and 1990. Changes in ethnic classification account for most of the change. In the
      1980 count, 10 states with historically large Indian populations account for 53%
      of births of Indians between the ages of 10 and 80, compared with 72% of the
      first enumerations of the same cohorts. Migration further reduced the share of
      these states to 46% of Indian residents in these cohorts. Study of the dispersal
      of the Indian population should focus primarily on the new emergence of the
      expression of Indian identity, rather than on migration from former population
      centers.

PMID- 8262286
TI  - A joint model of marital childbearing and marital disruption.
AB  - Married couples with children appear to be less likely to end their marriages
      than childless couples, especially when the children are young. Although this
      suggests that children affect the chances that their parents will divorce, the
      process may not be so simple: the chances that the marriage will last also may
      affect couples' willingness to make the commitment to the marriage implied by
      having children. This paper uses data from the Panel Study of Income Dynamics
      (PSID) to test the hypothesis that the risk of disruption faced by a married
      woman affects the chances that she will conceive and bear a child. The model used
      takes into account the simultaneous relationships between marital dissolution and
      marital fertility by including the hazard of disruption as a predictor of timing
      and likelihood of marital conception, and by including the results of previous
      fertility decisions as predictors of disruption of the marriage. We find that the
      hazard of disruption has strong negative effects on the hazard of marital
      childbearing, lengthening the intervals between births and decreasing the chances
      that a child will be born. This effect appears to be strongest for women who have
      had at least one child, either before or during the current marriage, although it
      is also large for childless women. Explicitly including the hazard of disruption
      in models of marital childbearing has sizable and important effects on many
      predictors of fertility.

PMID- 8262287
TI  - A portrait of the nest-leaving process in early adulthood.
AB  - This paper provides an in-depth portrait of the nest-leaving process in early
      adulthood as it emerged in the 1980s. Event histories are used to describe
      transitions in and out of the parental home during the years from age 15 through
      age 23. We focus on the role of the "new" forms of living arrangements in the
      leaving-home process, namely nonfamily living and cohabitation. The results show
      that the transition to full residential independence is more gradual, with more
      intermediate steps, than previous studies suggested. Cohabitation is rare as a
      route out of the parental home, and both nonfamily living and cohabitation lead
      to much higher return rates than does marriage.

PMID- 8262288
TI  - Simplicity and complexity in the effects of parental structure on high school
      graduation.
AB  - As more and more children experience nonintact families because of nonmarital
      birth or parental marital disruption, researchers have paid more attention to
      whether nonintact family experiences have negative effects on later life. This
      study uses data from the National Longitudinal Survey of Youth to consider how
      experiences of parental structure affect chances of high school graduation. The
      study shows that the negative effects of parental structure are simpler than
      theoretical notions might suggest.

PMID- 8262289
TI  - Enforcing divorce settlements: evidence from child support compliance and award
      modifications.
AB  - This paper uses an implicit contracting framework to understand the dynamic
      nature of divorce settlements and to analyze the determinants of noncompliance
      with child support awards. In addition to the standard economic variables that
      affect the noncustodial parent's (NCP's) ability to pay child support, our
      approach focuses on factors that may affect the NCP's desire to pay, such as the
      ongoing relationship between the two parents and between the NCP and the
      children. We also examine the "state-contingent" nature of child support payments
      and explore the factors that lead to modifications in child support agreements.
      Using a longitudinal data set collected by the Stanford Child Custody Project,
      the empirical analysis provides documentation that compliance by noncustodial
      fathers can vary substantially from month to month. In addition, we find that
      even within a short period after divorce, a substantial minority of parents agree
      to make informal modifications to their divorce settlement in response to changes
      in economic circumstances and in custodial arrangements.

PMID- 8262290
TI  - The slowing metabolism of marriage: figures from 1988 U.S. marital status life
      tables.
AB  - Marital status life tables for the United States, 1988, show a continuing retreat
      from marriage. For both sexes, the proportion ever marrying declined and the
      average age at first marriage rose. The 1988 rates imply that 43% of marriages
      end in divorce. That represents a slight decline from the 1983 figure, and
      suggests that divorce has peaked at a level below that estimated in earlier
      analyses.

PMID- 8262291
TI  - Two different regimens of preinduction ripening of the uterine cervix with
      prostaglandin E2: a randomized clinical study.
AB  - A randomized clinical study was designed to test the relative efficacy of
      preinduction cervical ripening with 0.25 mg prostaglandin E2 (PGE2), repeated if
      necessary (group 1) compared to a single maturation with 0.50 mg PGE2 (group 2).
      In group 1 (n = 42), the ripening process was repeated every day until
      spontaneous onset of labor occurred or induction with oxytocin was decided (for
      improved Bishop score above 5, or maternal or fetal distress). In group 2 (n =
      42) the patients who had not labored 12 h after the maturation procedure had
      labor induced with oxytocin, irrespective of their cervical status. In group 1,
      28 patients experienced repeated maturations (from 2 to 9). Thirty patients had
      an induction of labor with oxytocin in group 2 and only 12 in group 1 (P <
      0.0001). There were four failures of induction of labor in group 2 and none in
      group 1 (P < 0.05). Three episodes of myometrial hyperstimulation requiring an
      emergency cesarean section for acute fetal distress occurred in group 2 and none
      in group 1. There were 13 cesarean sections in group 2 and eight in group 1. The
      outcome of pregnancy was otherwise similar in both groups. In order to avoid
      failure of induction of labor, pre-induction cervical ripening with 0.25 mg PGE2,
      repeated daily if necessary, is therefore recommended in high risk pregnancy
      unless a severe maternal or a fetal distress call for a prompt delivery
      irrespective of the cervical status.

PMID- 8262292
TI  - Antibiotic prophylaxis against postpartum endometritis after vaginal delivery: a
      prospective randomized comparison between Amox-CA (Augmentin) and abstention.
AB  - The most common adverse outcome associated with vaginal delivery is endometritis.
      It plays a significant role in postpartum morbidity and mortality. There is
      considerable evidence to support the idea that a single dose of antibiotic after
      vaginal delivery might decrease the incidence of postpartum endometritis. In this
      study the evaluation of the efficacy of antibiotic prophylaxis was based upon
      comparison of a group of patients given a single dose of Amox-CA (Augmentin) with
      a group of patients without treatment. The study was performed in the Department
      of Obstetrics and Gynecology of the A. Beclere Public Hospital, Clamart, France
      (Paris-Sud University). The patients who were the subject of the study had
      delivered vaginally during the period of 1 year, and were free of any clinical
      diagnosis of chorioamnionitis or other extragenital infection, had a maternal
      temperature of less than 38 degrees C during labor and 1 h after delivery, and
      had no history of allergy to penicillins or cephalosporins. After application of
      exclusion criteria, 1373 patients were randomized and 1291 included 610 in Group
      I given Amox-CA and 681 in Group II without any antibiotic. A single dose of 1.2
      g of Amox-CA was given by intravenous injection, 1 h after delivery, in Group I.
      Patients of Group II received no injection. Postpartum status was evaluated
      before the patient left hospital and 2 weeks later. The two groups were similar
      in terms of demographic and clinical parameters. Four patients developed
      endometritis in Group I (4/610, 0.66%). Sixteen patients in Group II developed
      endometritis (16/680, 2.38%) (P = 0.013; 95% confidence interval (CI), 0.36
      3.08%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262293
TI  - Prenatal diagnosis of fetal cerebral abnormalities by ultrasonography and
      magnetic resonance imaging.
AB  - We found magnetic resonance imaging (MRI) of the fetal brain to be effective in
      confirming or denying diagnosis of fetal cerebral defects when ultrasonography
      was inconclusive or incomplete. In this paper we describe 31 cases in which
      ultrasonographic evidence of fetal brain defects was verified by MRI. MRI was
      performed after curarization of the fetus. In 21 cases, ultrasonographic evidence
      was confirmed by histological study of the fetus or postnatal radiological
      examination. In 10 cases, ultrasonographic diagnosis was denied by MRI and
      healthy infants were born. In one case of cerebral toxoplasmosis, ultrasonography
      detected periventricular calcifications but MRI was normal. In 20 cases MRI
      ascertained or further documented the ultrasonographic findings. However in 4 of
      these 20 cases autopsy of the fetus was required to determine the exact nature of
      the lesion.

PMID- 8262294
TI  - Intra-amniotic pressure is not affected by amniocentesis between 13 and 18 weeks
      of gestation.
AB  - Changes in amniotic fluid pressure before and after amniocentesis fell within the
      range of +/- 5 mmHg, except when uterine contractions were present. Intra
      amniotic pressure is not affected by amniocentesis between 13 and 18 weeks of
      gestation. Amniotic fluid pressure was recorded in 82 pregnancies of patients
      undergoing genetic amniocentesis to determine whether sampling of amniotic fluid
      between 13 and 18 weeks changed intra-amniotic pressure. Pressures were recorded
      through a needle and saline filled catheter with a zero-level at the needle tip.
      Amniotic fluid pressure was unrelated to gestational age (P = 0.962) during the
      weeks we performed our measurements. Fluid samples of 12.6% of the total volume
      in a group of early genetic amniocentesis (n = 65) and of 7.5% of the total
      volume in a group of late genetic amniocentesis (n = 17) did not change
      significantly amniotic fluid pressure values. An increase in pressure of more
      than 5 mmHg only occurred in cases where uterine contractions were present. Other
      than these cases, all pressure change values fell within the range of +/- 5 mmHg.
      No difference in pregnancy outcome were present within the two groups. An
      argument for a standard method for stationing pressure is presented.

PMID- 8262295
TI  - Poor antenatal care and pregnancy outcome.
AB  - OBJECTIVES: To characterize women receiving poor antenatal care and assess their
      perinatal risk. DESIGN: Computerized data. SETTING: Public hospital setting Paris
      (1987-1990). Comparison with representative sample in Ile-de-France region (n =
      6423). METHODS: Poor attenders with less than 3 visits (n = 210) were compared
      with good attenders with 3 visits or more (n = 5631). RESULTS: Poor attenders
      were younger and had higher rates of perinatal mortality (4.7%), preterm delivery
      (Odds ratio 5.2:4.3-6.3) and low birth weight (Odds ratio 4.6:3.7-5.6).
      CONCLUSION: Women with poor antenatal care have a greater risk for adverse
      pregnancy outcome. This risk cannot be attributed to unfavourable living
      conditions only.

PMID- 8262296
TI  - Balance of amino acids in the pregnant human uterus at term.
AB  - The nutritive and metabolic state of the human uterus at term is evaluated by
      measuring the uptake and release of amino acids. The subjects are ten healthy
      women with normal pregnancy undergoing elective caesarean section at term, before
      onset of labour. Free amino acids in arterial (radial artery) and venous (plexus
      of the uterine and ovarian veins) blood are determined and arteriovenous (AV)
      differences in each amino acid across the uterus are calculated. Generally the AV
      differences are negative, i.e. uterus at term releases amino acids in most cases.
      The human pregnant uterus at term is characterized by a release of amino acids
      rather than uptake. This indicates that they are in excess and are not needed in
      anabolic processes or as a fuel, even when the uterine tissue at term is supposed
      to be preparing for its grand performance, i.e. the delivery.

PMID- 8262297
TI  - Abdominal ultrasound combined with histological and cytological fine needle
      biopsy of suspected ovarian tumors.
AB  - To investigate, in a population of women suspected of an ovarian mass, whether
      pelvic ultrasound (US) and US combined with US-guided fine needle biopsy (FNB)
      increased the detection rate and whether tumor specific diagnoses could be
      obtained, a cohort of 307 patients suspected of an ovarian mass underwent US
      examination as part of routine gynecologic work-up. In cases of solid or
      solid/cystic lesions a US guided FNB for histology as well as cytology was
      proposed. All 35 primary ovarian cancers, 6 of 7 secondary ovarian cancers, and 3
      of 4 non-ovarian cancers were demonstrated on US. Among 17 cases with normal
      palpation and an ovarian mass on US, operation disclosed 3 ovarian cancers. FNB
      identified 24 of 27 primary ovarian cancers and 7 of 7 cancers of extra-ovarian
      origin. The use of US, in this study, increased the detection of masses in the
      pelvis and FNB provided a reliable verification.

PMID- 8262298
TI  - Efficacy of a synthetic mesh sling in keeping the small bowel in the upper
      abdomen to prevent radiation enteropathy in gynecologic malignancies.
AB  - Radiation therapy in gynecological malignancies is limited by the frequent
      occurrence of radiation enteropathy at effective dose levels of 45 Gy and higher.
      Elevation of the small bowel out of the true pelvis should enable doses of up to
      60-70 Gy to be given without damaging the small bowel. We report a feasibility
      study concerning elevation of the small bowel out of the true pelvis, by creating
      an intra-abdominal sling with a synthetic mesh. Twelve patients with pelvic
      gynecological malignancies were included since 1986. In all patients peroperative
      application of the mesh was possible. In ten patients adequate elevation of the
      small bowel was achieved. Two patients showed a right-sided herniation of a small
      bowel loop on a control barium opacification, performed 1 week postoperatively.
      In one of these a fistula occurred after resecuring the mesh. The most important
      problem in this study, as has also been reported elsewhere, was a herniation of a
      small bowel loop. The incidence is probably inversely correlated with the skill
      of the surgeon and will therefore be reduced with increasing experience. Future
      long-term studies should address the issue whether or not radiation enteropathy
      can be prevented by this method.

PMID- 8262299
TI  - Immunosuppressive 30-kDa protein in urine of pregnant women and patients with
      trophoblastic diseases.
AB  - Urine samples obtained from normal pregnant women and patients with trophoblastic
      diseases contain 30-kDa protein that suppresses phytohemagglutinin-induced T cell
      proliferation. The immunosuppressive protein was measured by a newly developed
      radioimmunoassay. The 30-kDa protein was demonstrated in almost all urine samples
      examined, fluid from hydatid vesicles and chorionic extracts, but not in any
      serum samples except at low levels in some sera from patients with
      choriocarcinoma. During pregnancy, the level of urinary 30-kDa protein was higher
      in the first (1625.5 +/- 1212.0 ng/ml, mean +/- S.D.) and second (1457.4 +/-
      1332.4 ng/ml) trimesters than in the third trimester (460.6 +/- 419.0 ng/ml). The
      urinary 30-kDa protein/hCG ratios in patients with choriocarcinoma (8.3 +/- 10.9)
      were significantly higher than those in patients with hydatidiform mole (0.67 +/-
      1.00, P < 0.01) and in all trimesters than those of normal pregnant women (0.54
      +/- 0.44 in first trimester, P < 0.05; 0.63 +/- 0.46 in the second trimester, P <
      0.05; 0.24 +/- 0.17 in the third trimester, P < 0.01). There is no significant
      difference between the ratios in hydatidiform mole and normal pregnancy. These
      findings and the fast disappearance of the 30-kDa protein from the circulation
      suggest that the 30-kDa protein plays a part in proliferation of trophoblastic
      cells in, or their invasion into the host by locally suppressing the immune
      reaction of the host and that the increase in the urinary 30-kDa protein level,
      in cases of choriocarcinoma, may be due to the malignant transformation of
      trophoblastic cells resulting in their rapid invasion.

PMID- 8262300
TI  - Nipple discharge and abnormal galactogram. Results of a long-term study (1964
      1990).
AB  - In case of abnormal nipple discharge of the female breast, galactography can
      detect variations of ductal calibre, intraductal alterations and ductal
      discontinuities. Between 1964 and 1990 we examined 2588 women by galactography
      and performed 826 duct excisions. In one out of 8 patients (13.4%) we diagnosed
      invasive carcinoma or ductal carcinoma in situ. In more than 40% a solitary
      ductal papilloma was detected. 13.7% of the patients were found to have extensive
      intraductal solid papillary or adenomatous epithelial proliferations. Comparison
      with collected statistical data reveals that other investigators are able to
      detect malignant changes in 1-23% of cases. We have managed the largest number of
      cases and have diagnosed pathologic ductal secretion in more than 3% of women we
      screened by physical inspection, mammography and sonography. The colour of the
      ductal discharge is of minor importance, as histologic analysis is mandated by
      the presence of ductal system alterations.

PMID- 8262301
TI  - Molecular cytogenetics: applications in clinical genetics.
AB  - To illustrate the advantage of fluorescence in situ hybridization (FISH) in
      clinical genetics, we have chosen six clinical cases from our routine laboratory
      where we have used molecular cytogenic techniques to optimise the cytogenetic
      analysis. Using centromere-specific DNA probes and whole chromosome DNA libraries
      either obtained from somatic cell hybrids or generated from flow-sorted
      chromosomes, we have been able to identify small marker chromosomes, chromosomal
      duplications and inversions, to determine the ploidy in interphase nuclei, and to
      characterize subtle chromosomal translocations. We conclude that molecular
      cytogenetics is a valuable technique that should be used as a supplement to
      conventional cytogenetics to reduce the number of unresolved karyotypes in
      clinical genetics.

PMID- 8262302
TI  - Prostacyclin, thromboxane and antioxidant levels in pregnancy-induced
      hypertension.
AB  - 1. Plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF 1 alpha, a major metabolite
      of prostacyclin), plasma thromboxane B2 (TXB2, a major metabolite of thromboxane
      A2) and five antioxidants (indirect markers of reactive oxygen species) namely,
      plasma thiol, erythrocyte lysate thiol, erythrocyte superoxide dismutase, plasma
      total glutathione and erythrocyte membrane thiol, were measured in 25 healthy non
      pregnant women, 36 normotensive pregnant women and 35 women with pregnancy
      induced hypertension (PIH). 2. The levels of TXB2 were significantly increased in
      normal pregnant women and PIH women with or without proteinuria compared with non
      pregnant women. The concentrations of TXB2 in PIH women with proteinuria were
      higher than those without proteinuria (P < 0.05). 3. The levels of 6-keto-PGF1
      alpha in healthy non-pregnant women and PIH women with or without proteinuria
      were significantly lower than that in normotensive pregnant women (all of three P
      < 0.01). There were no significant differences between healthy non-pregnant women
      and PIH women with and without proteinuria. 4. The ratio of TXB2 to 6-keto-PGF1
      alpha was markedly elevated in PIH women with or without proteinuria compared
      with normotensive pregnant women and healthy non-pregnant women. The difference
      between PIH women with proteinuria and those without proteinuria was not
      significant (P > 0.05). 5. The levels of plasma thiol, superoxide dismutase and
      glutathione were significantly decreased in PIH women compared with normotensive
      pregnant women. 6. There were significant positive correlations between the
      levels of prostaglandins and antioxidant activity.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8262303
TI  - Reversal of diabetic related accelerated fetal growth by maternal glycaemic
      control.
AB  - In a young woman with insulin-dependent diabetes mellitus, poor diabetic control
      during the second trimester of pregnancy resulted in ketoacidosis, accelerated
      fetal growth and polyhydramnios. With the establishment of tight maternal
      glycaemic control, both accelerated intrauterine growth and polyhydramnios were
      reversed and a good pregnancy outcome resulted.

PMID- 8262304
TI  - Adenomatoid tumor of the uterus.
AB  - A case of adenomatoid tumor of the uterus of a 49-year-old woman is described.
      The tumor was unusually large and atypically located in the fundus of the uterus.
      Adenomatoid tumors in genitals are benign but may macroscopically resemble a
      malignant tumor. As recurrence does not occur simple excision is sufficient.

PMID- 8262305
TI  - Re: W. Bonds et al., preliminary report of unexpected local reactions to a
      progestogen-releasing contraceptive vaginal ring. Eur J Obstet Gynaecol Reprod
      Biol 1993; 48: 123-125. Comment.

PMID- 8262306
TI  - Activation of protein kinase C in glomerular cells in diabetes. Mechanisms and
      potential links to the pathogenesis of diabetic glomerulopathy.
AB  - Protein kinase C (PKC) is activated in rat renal glomerulus within a week of
      induction of experimental diabetes. Studies in isolated glomeruli and in cultured
      endothelial and mesangial cells have demonstrated that high ambient
      concentrations of glucose activate PKC and thus implicate hyperglycemia per se as
      a mediator of PKC activation in glomerular cells in diabetes. High glucose
      concentrations activate PKC by increasing cellular levels of diacylglycerol
      (DAG), the major endogenous modulator of this signalling system. In contrast to
      physiological extracellular stimuli of PKC that increase cellular DAG levels by
      receptor-mediated enhancement of membrane inositol phospholipid hydrolysis, in
      glomerular cells high concentrations of glucose increase DAG by de novo synthesis
      from glycolytic intermediates. Activation of PKC by glucose or other agonists
      increases the permeability of endothelial cells to albumin and stimulates matrix
      protein synthesis in mesangial cells; it thereby may be involved in the
      pathogenesis of both the functional and structural alterations of the glomerulus
      in diabetes. Recent studies in isolated glomeruli from diabetic rats have also
      implicated activation of PKC in suppression of nitric oxide (NO)-mediated
      increases in glomerular cGMP generation in response to cholinergic stimuli. In
      mesangial cells, cGMP suppresses PKC-mediated increases in matrix protein
      synthesis. Thus, impaired NO-mediated cGMP generation in glomeruli of diabetic
      individuals may amplify matrix protein synthesis in response to hyperglycemia and
      other stimuli of PKC. These and other observations suggest that activation of the
      PKC system by hyperglycemia may represent an important pathway by which
      glucotoxicity is transduced in susceptible cells in diabetes.

PMID- 8262307
TI  - Factors responsible for impaired fibrinolysis in obese subjects and NIDDM
      patients.
AB  - Accelerated atherosclerosis is the leading cause of death in patients with non
      insulin-dependent diabetes mellitus (NIDDM). Impaired endogenous fibrinolytic
      activity may accelerate atherosclerosis by exposing vascular luminal wall
      surfaces to persistent and recurrent thrombi and clot-associated mitogens. This
      study was conducted to further characterize endogenous fibrinolysis in lean and
      obese nondiabetic subjects and in NIDDM patients and to identify mechanisms
      responsible for the alterations identified. Obese and diabetic subjects had
      threefold elevations of plasma concentrations of plasminogen activator inhibitor
      type 1 (PAI-1) compared with values in lean control subjects. Despite the lack of
      significant differences in plasma concentrations of tissue-type plasminogen
      activator in the obese and diabetic subjects, both basal and stimulated
      endogenous fibrinolytic activities were decreased. The decreases were associated
      with increased activity of PAI-1 in plasma, in turn correlated with increased
      concentrations of immunoreactive insulin and C-peptide. These results are
      consistent with our previous observations demonstrating direct stimulatory
      effects of insulin and its precursors on cellular expression of PAI-1 in vitro
      and observations by others demonstrating decreased basal fibrinolytic activity in
      NIDDM patients. Impaired endogenous fibrinolytic activity could lead to prolonged
      or recurrent exposure of luminal surfaces of vessel walls to microthrombi and
      clot-associated mitogens that may accelerate atherosclerosis in hyperinsulinemic
      subjects.

PMID- 8262308
TI  - Delayed onset of insulin activation of the insulin receptor kinase in vivo in
      human skeletal muscle.
AB  - During the infusion of insulin in vivo, the rate of activation of glucose
      disposal lags significantly behind the rate of increase in serum insulin levels.
      To determine whether this delay was related to transcapillary transport of
      insulin, we determined increments in serum insulin levels, glucose disposal rates
      (GDR), and insulin receptor (IR) kinase activity measured during continuous
      infusions of insulin (40 and 120 mU.m-2.min-1) administered to 8 nondiabetic
      males; similar studies were done at 1,200.m-2.min-1 in 2 of the subjects. Half
      maximal insulin levels were achieved at a mean of 4.9 and 7.2 min during the 40
      and 120 mU.m-2.min-1 clamps, respectively, with corresponding half-maximal GDR
      stimulation at a mean of 59 and 47 min. Unlike the rise in insulin levels, IR
      kinase activation was much slower with half-maximal activity occurring at
      approximately 40-60 min in the 2 clamps. Thus, the rise in serum insulin levels
      in each clamp was much faster than the increment in either kinase activity or
      glucose disposal. Insulin infusion increased both IR kinase and GDR maximally
      approximately 10-fold, with half-maximal stimulation at approximately 3,600 and
      approximately 700 pM, indicating spare kinase for glucose disposal. These results
      demonstrate that the delay in stimulation of glucose disposal by insulin is
      related to a rate-limiting step between the intravascular space and the cell
      surface of skeletal muscle. This may involve delayed transendothelial transport
      of insulin.

PMID- 8262309
TI  - Identification in islets of Langerhans of a new rat alpha 2-adrenergic receptor.
AB  - The islets of Langerhans are richly innervated, and an inhibitory effect on
      insulin secretion, mediated through alpha 2-adrenergic receptors, appears to be
      an important physiological neural modulator of beta-cell function. An alpha 2
      receptor was cloned from isolated newborn rat islets using a polymerase chain
      reaction (PCR) approach. This receptor was shown by sequencing to be a new rat
      alpha 2-receptor very similar to the human alpha 2-C2 receptor. No other alpha 2
      receptor subtype was identified in normal islets by the PCR using alpha 2
      receptor primers. This was also the only alpha 2-receptor subtype present in the
      exocrine pancreas and liver. In contrast, in the beta-cell line, beta TC3, the
      alpha 2-C2 receptor was not detected, but the alpha 2-C4 and alpha 2-C10 receptor
      subtypes were detected. It is suggested that the alpha 2-C2 subtype may be the
      principal alpha 2-receptor mediating inhibitory autonomic nervous system activity
      in the gastrointestinal tract. A comparison of the rat islet, pancreas, and liver
      alpha 2-receptor sequences reported here with previously reported alpha 2
      receptor sequences indicates that the rat islet alpha 2-receptor is not the rat
      alpha 2-C2 homologue previously denoted as RNG alpha 2, but is a new, fourth rat
      subtype with an even higher similarity to the human alpha 2-C2 receptor.

PMID- 8262310
TI  - Predictive value of lymphocyte antibodies for the appearance of diabetes in BB
      rats.
AB  - Lymphocyte antibodies have been described in autoimmune disorders, including
      insulin-dependent diabetes mellitus (IDDM). We have developed a quantitative
      method to measure autoantibodies directed against T-lymphocytes, based on two
      color fluorescence labeling of Wistar mononuclear cells and analysis of
      fluorescence by flow cytometry. The lymphocyte antibody levels were determined
      retrospectively in the serum of 73 BB and 18 Wistar rats. We demonstrated the
      binding of the lymphocyte autoantibodies of both CD4+ and CD8+ T-cells.
      Lymphocyte antibodies were present in 90% of the BB rats at diabetes onset,
      compared with 11% of the Wistar rats. At 75 days of age, 83% of the BB rats,
      which later became diabetic, were positive for the lymphocyte antibodies,
      compared with 15% of their littermates who maintained a normal glucose tolerance.
      In all cases, the antibodies were of the immunoglobulin M isotype. We conclude
      that lymphocyte antibodies are present before diabetes onset and, using this
      method, that their presence can predict the development of diabetes with a
      sensitivity of 83% and a specificity of 85% in BB rats.

PMID- 8262311
TI  - Associations of anti-GAD antibodies with islet cell antibodies and insulin
      autoantibodies in first-degree relatives of type I diabetic patients.
AB  - Sera from 114 first-degree relatives of insulin-dependent diabetes mellitus (type
      I diabetes) patients and 81 healthy individuals living in Germany were analyzed
      for antibodies to rat brain glutamic acid decarboxylase (GAD-ab) using an
      immunoprecipitation assay. The determination of GAD-ab in the 81 islet cell
      antibody (ICA) and insulin autoantibody (IAA) negative healthy individuals
      established a normal range (mean +/- 2 SD); 2 healthy individuals (2.5%)
      possessed GAD-ab levels above this range, but became negative on follow-up. None
      of 86 ICA-/IAA- first-degree relatives had GAD-ab; whereas, 42.9% of 28 ICA+
      and/or IAA+ relatives were positive for GAD-ab. Presence of GAD-ab was negatively
      correlated with IAA (P = 0.02) and positively with ICA (P = 0.0006). Follow-up
      samples were obtained from 25 of 28 ICA+ and/or IAA+ relatives with a mean (+/-
      SD) follow-up period of 20.6 +/- 12.1 months. In these 25 relatives, GAD-ab were
      positive in 70% ICA+/IAA-, 0% ICA-/IAA+, and 57.1% ICA+/IAA+ relatives in the
      first sample and in 57.1% ICA+/IAA-, 0% ICA-/IAA+, and 70% ICA+/IAA+ relatives in
      the last sample. GAD-ab, once detected, persisted in 9 of 11 GAD-ab+ relatives.
      Of the relatives, 2 converted to GAD-positivity, concomitant with the appearance
      of ICA, and 2 others lost GAD-ab during follow-up. Of the 28 ICA+ and/or IAA+
      relatives, 6 progressed to overt type I diabetes on follow-up, and GAD-ab were
      detectable in 4 of these relatives.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262312
TI  - Induction of tolerance to islet xenografts in a concordant rat-to-mouse model.
AB  - Induction of tolerance to concordant rat islet xenografts (150 Wistar-Furth [WF]
      islets) in streptozocin-induced (STZ) diabetic mice (C57BL/6) was determined at
      three different sites for islet implantation (thymus, kidney capsule, and liver).
      Islets transplanted into the thymus or kidney capsule were either fresh or
      cultured at 24 degrees C for 7 days, and the mice received a single injection of
      either anti-mouse lymphocyte serum (MALS) alone or anti-rat lymphocyte serum
      (RALS) and MALS. Islets transplanted into the liver via the portal vein were
      cultured at 24 degrees C for 7 days, and the mice received a single injection of
      MALS and RALS. To document the induction of tolerance, recipients with islet
      xenografts surviving > 100 days were made diabetic again by STZ (thymus and
      liver) or nephrectomy (kidney capsule) and received a second transplant of 150
      fresh WF islets in the kidney capsule. Kidney capsule placement of fresh or
      cultured islets with MALS alone or MALS and RALS did not induce tolerance in a
      significant number of recipients. The intrathymic transplantation of fresh or
      cultured islets with MALS alone resulted in prolonged WF islet xenograft survival
      (mean survival time of 39.7 +/- 7.9 days) but did not result in tolerance,
      whereas the administration of MALS and RALS with the intrathymic placement of
      fresh or cultured islets induced tolerance in approximately 50% of the mice.
      Intrahepatic transplantation of cultured islets with MALS and RALS resulted in
      tolerance to donor islets in 90% of the recipients. Donor specificity was
      evaluated by a third major histocompatibility complex-disparate fresh Lewis islet
      xenograft.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262313
TI  - Maternal component in NIDDM transmission. How large an effect?

PMID- 8262314
TI  - Isolation of nonobese diabetic mouse T-cells that recognize novel autoantigens
      involved in the early events of diabetes.
AB  - Insulin-dependent diabetes mellitus (IDDM) is thought to result from chronic,
      cell-mediated, autoimmune islet damage. Our aim was to identify the earliest T
      cell autoantigen in IDDM, reasoning that this antigen could be causally involved
      in the initiation of the disease. Identification of the earliest beta-cell
      specific autoantigen is extremely important in allowing advances in prevention
      and treatment of initial events in the development of inflammatory insulitis that
      precedes beta-cell destruction and overt diabetes. Therefore, we analyzed the
      proliferative responses of peripheral T-cells from young, female nonobese
      diabetic (NOD) mice to extracts of pancreatic beta-cell lines. We were able to
      demonstrate that T-cells responsive to beta-cell antigens exist in the peripheral
      lymphoid tissue of these mice in the absence of deliberate priming before the
      manifestation of histologically detectable insulitis. T-cell lines and clones
      isolated from the peripheral lymphatic tissues of young, unimmunized, female NOD
      mice were also shown to react with extracts of beta-cells. Fractionation of the
      beta-cell extracts showed that these T-cell clones recognized multiple beta-cell
      specific autoantigens but none of the previously reported putative autoantigens
      (glutamic acid decarboxylase [GAD]65, GAD67, Hsp65, insulin, ICA 69,
      carboxypeptidase-H, and peripherin). Thus, we can conclude that these responses
      are specific for novel beta-cell autoantigens. Finally, NOD T-cell proliferative
      responses were also seen to an extract of human islets suggesting potential
      shared antigenic determinants between human and mouse beta-cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8262315
TI  - Abnormal insulin secretion, not insulin resistance, is the genetic or primary
      defect of MODY in the RW pedigree.
AB  - Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent
      diabetes mellitus (NIDDM) associated with autosomal-dominant inheritance. In the
      RW pedigree, MODY is associated with polymorphic DNA markers on chromosome 20q.
      To determine the early abnormalities of insulin action and insulin secretion in
      MODY, we studied nondiabetic members of the RW pedigree with and without the gene
      marker. Six nondiabetic marker-negative and 5 nondiabetic marker-positive members
      of the RW pedigree were studied, as were 4 diabetic marker-positive family
      members. Unrelated, young, healthy subjects served as comparison groups. Insulin
      action and insulin secretion were assessed with a frequently sampled intravenous
      glucose tolerance test. Insulin secretion was further assessed during constant
      glucose infusion by deconvolution of plasma C-peptide and by pulse analysis. The
      nondiabetic marker-positive group had normal sensitivity to insulin and
      unimpaired acute insulin response to intravenous glucose (AIRglu). However, the
      nondiabetic marker-positive group had decreased mean plasma C-peptide
      concentration and reduced absolute amplitude of insulin secretory oscillations
      during prolonged glucose infusion. These responses to prolonged glucose infusion
      were similar to those observed in the diabetic group. No alterations of insulin
      secretion were observed in the nondiabetic marker-negative family members.
      Deranged and deficient insulin secretion, and not insulin resistance, appears to
      be the genetic or primary abnormality that characterizes nondiabetic individuals
      who are predisposed to MODY in the RW pedigree.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262316
TI  - Peculiar T-cell signaling does not preclude positive selection in the diabetes
      prone BB rat.
AB  - Various studies have provided evidence that peripheral T-cells from the diabetes
      prone BB-DP rat are abnormal in function and cell surface phenotype. These
      characteristics have often been interpreted as indicators of immaturity and/or
      short life span. In this study, we describe a CD4-dependent signaling abnormality
      in BB-DP peripheral T-cells. In spite of the fact that CD4 plays a critical role
      in thymocyte development, the abnormal signaling does not appear to influence
      thymocyte development at the stage when the T-cell receptor is rearranged and the
      recombinase enzymes RAG-1 and RAG-2 transcripts are downregulated. Therefore, if
      a maturation defect leading to the seeding of the periphery with immature T-cells
      occurs in the BB-DP rat, it does not preclude the initial selection of the self
      major histocompatibility complex-restricted T-cell repertoire.

PMID- 8262317
TI  - Biological actions of insulin are differentially regulated by glucose and insulin
      in primary cultured adipocytes. Chronic ability to increase glycogen synthase
      activity.
AB  - We have shown previously that prolonged exposure to insulin and glucose impairs
      the insulin-responsive glucose transport system in primary cultured adipocytes.
      To assess the ability of insulin and glucose to regulate other cellular insulin
      actions, epididymal rat adipocytes were cultured in media containing 0-15 mM D
      glucose and with or without insulin (50 ng/ml). After 24 h, cells were washed and
      basal and maximally insulin-stimulated rates of 2-deoxy-D-glucose uptake, L
      leucine incorporation into protein, glucose oxidation to CO2, glucose
      incorporation into lipids, and glycogen synthase activity were measured. The
      results confirmed that glucose potentiates insulin's chronic ability to decrease
      basal and maximal glucose transport rates by approximately 50% at 5 mM glucose
      and by approximately 70% at 15 mM glucose compared with control cells. However,
      neither glucose nor insulin, alone or in combination, affected rates of leucine
      incorporation into protein. In addition, basal and maximal rates of glucose
      oxidation and of glucose incorporation into lipids were not regulated by glucose,
      and maximal responses declined approximately 50% over 24 h only when insulin was
      not present during preincubation (i.e., chronic insulin exposure was necessary to
      maintain full maximal responses). Glycogen synthase activity was measured in a
      cell-free system (0.5 mM UDP-glucose, with 10 or 0.01 mM glucose-6-phosphate)
      after exposing intact cells to glucose and insulin. Both short-term (1 h) and
      long-term (24 h) exposure to glucose alone led a dose-dependent increase in I
      form and D-form glycogen synthase activity. Chronic exposure to insulin also
      increased total glycogen synthase activity (I- plus D-form) but did not affect
      absolute rates of maximally stimulated I-form activity. Glucose (but not insulin)
      increased the cellular content of immunoreactive glycogen synthase by 70% after 1
      h. These results show that 1) chronic exposure to glucose and insulin impairs
      insulin responsiveness of the glucose transport system but does not affect rates
      of amino acid incorporation into protein; 2) the chronic presence of insulin is
      necessary for the maintenance of normal maximally stimulated rates of glucose
      oxidation and of glucose incorporation into lipids in cultured cells; and 3)
      glucose increases both D-form and I-form glycogen synthase activity, in part by
      increasing the amount of synthase protein, whereas chronic insulin exposure
      increases total glycogen synthase activity without altering maximal absolute
      rates of I-form activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8262318
TI  - Maternal effect and familial aggregation in NIDDM. The CODIAB Study. CODIAB
      INSERM-ZENECA Study Group.
AB  - Non-insulin-dependent diabetes mellitus (NIDDM) is known to have a strong genetic
      basis, but the mode of inheritance is still unknown. Recent studies have
      suggested that maternal inheritance is important; this complicates the
      transmission pattern of NIDDM. In our study, the familial aggregation of diabetes
      and the maternal effect were investigated through three generations. The CODIAB
      Study recruited 536 NIDDM patients between 35 and 74 years of age from 10
      diabetes centers in France. Familial aggregation was confirmed: among 218 NIDDM
      patients, 66% had at least one diabetic relative. Mothers were implicated 2 times
      more frequently than fathers (P < 0.001). This maternal effect was confirmed
      because more diabetic cases were noted among maternal than paternal aunts and
      uncles (P < 0.02). When we considered the next generation, women had more
      diabetic offspring than men (P < 0.01). Other factors susceptible to modify the
      familial aggregation were considered. The maternal effect was not significantly
      related to the patients' ages (P > 0.2). The genetic component was more important
      when the diagnosis was made earlier, but the maternal effect was homogeneous (P >
      0.3). In conclusion, we found a familial aggregation of diabetes that suggests a
      strong genetic component with a mode of inheritance that may be influenced by a
      maternal environment.

PMID- 8262319
TI  - Growth hormone induces resistance to the mitogenic action of insulin through
      local IGF-I. Studies in normal and Pygmy T-cell lines.
AB  - Growth hormone (GH) and insulin have both mitogenic and metabolic actions. The
      growth-promoting effects of GH in vivo are thought to be mediated by insulin-like
      growth factor-I (IGF-I), whereas the metabolic effects of GH are thought to be
      either direct or mediated by factors other than IGF-I. In previous studies using
      HTLV-II-transformed T-lymphoblast cell lines established from normal individuals,
      we have shown that GH preincubation induces resistance to the growth-promoting
      (mitogenic) action of insulin. In this study, using T-cell lines from 3 American
      control subjects, 1 African control subject, and 1 African Pygmy (the latter
      previously shown to be resistant to the growth-promoting actions of both IGF-I
      and GH), we examined the role of local IGF-I in the mediation of GH-induced
      resistance to the mitogenic action of insulin. In these studies, we quantified
      the stimulation of T-cell colony formation in response to insulin in the presence
      and absence of either GH or IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262320
TI  - Effects of calcium antagonists on insulin-mediated glucose metabolism in skeletal
      muscle.
AB  - The effect of three calcium antagonists (verapamil, diltiazem, and nifedipine) on
      insulin effects was investigated in isolated rat soleus muscles. Soleus muscles
      were incubated in the presence of insulin (100 microU/ml), a concentration that
      stimulates the rates of lactate formation and glycogen synthesis half-maximally
      and with and without a calcium antagonist. A decrease (48%; P < 0.001) was noted
      in the insulin-mediated rate of glycogen synthesis by verapamil at 100 microM; no
      effect was observed at lower concentrations of verapamil. Diltiazem decreased the
      insulin-mediated rates of glycogen synthesis by 36 (P < 0.001), 64 (P < 0.001),
      and 73% (P < 0.001) at 1, 10, and 100 microM, respectively. Nifedipine decreased
      the insulin-mediated rates of glycogen synthesis by 37% at 0.1 microM (P <
      0.001), 36% at 1 microM (P < 0.001), 21% at 10 microM (P < 0.05), and 72% at 100
      microM (P < 0.001). Verapamil at 100 microM decreased lactate formation by 48% (P
      < 0.001). However, diltiazem increased the rate of lactate formation by 22 (P <
      0.01), 43 (P < 0.001), and 61% (P < 0.001) at 1, 10, and 100 microM,
      respectively. In contrast, nifedipine increased the insulin-mediated rate of
      lactate formation by 45% only at 100 microM (P < 0.01). The increased rate of
      lactate formation was probably caused by an increased rate of glycogenolysis,
      because high concentrations of all the calcium antagonists significantly
      decreased muscle glycogen content. The insulin-stimulated rate of 3-O-methyl-D
      glucose transport or cAMP content was not affected by diltiazem at 1 or 10
      microM. The results suggest that the calcium antagonists work by a mechanism,
      possibly by activating a calcium channel or an extracellular receptor, to
      influence markedly insulin-mediated intracellular glucose metabolism in skeletal
      muscle.

PMID- 8262321
TI  - Autoantibodies to glutamic acid decarboxylase in patients with IDDM and
      autoimmune thyroid disease.
AB  - Autoantibodies to glutamic acid decarboxylase (GAD), previously reported to be
      the 64,000-M(r) (64K) islet cell protein, were measured by a radioimmunoassay
      using purified pig brain GAD in 29 insulin-dependent diabetes mellitus (IDDM)
      patients with autoimmune thyroid disease (AITD) and in 29 sex- and disease
      duration-matched IDDM patients without AITD. Islet cell antibodies (ICAs) and 64K
      antibodies were also determined. In IDDM patients with short-duration diabetes (<
      1 year), the prevalence and levels of GAD antibodies were 100% (8 of 8) and 609
      +/- 166 U (means +/- SE), respectively, in IDDM patients with AITD and 81.8% (9
      of 11) and 90 +/- 51 U, respectively, in patients without AITD. In patients with
      long-standing IDDM (3-22 years), the prevalence and levels of GAD antibodies were
      76.2% (16 of 21) and 193 +/- 66 U, respectively, in patients with AITD and 50.0%
      (9 of 18) and 36 +/- 14 U, respectively, in patients without AITD. For up to 6
      years after the onset of IDDM, the levels of GAD antibodies in IDDM patients with
      AITD were significantly higher than in IDDM patients without AITD. A close and
      significant correlation was found between GAD antibodies and ICA or 64K
      antibodies in IDDM patients with AITD. Our results demonstrate that high levels
      of GAD antibodies were present in IDDM patients with AITD. The observed
      differences in GAD immunoreactivity between IDDM patients with and without AITD
      might help evaluate the role of GAD antibodies in IDDM.

PMID- 8262322
TI  - High genetic risk for IDDM in the Pacific Northwest. First report from the
      Washington State Diabetes Prediction Study.
AB  - A combination of immune, genetic, and metabolic markers potentially implicated in
      the development of insulin-dependent diabetes mellitus (IDDM) was studied in the
      general population. We screened 3,992 healthy schoolchildren, 12-18 years of age
      with no family history of IDDM, for islet cell antibodies (ICAs). Of the
      children, 69 (1.7%) were found to be ICA positive (ICA+), of whom 7 (0.17%) also
      were positive for insulin autoantibodies (IAAs). ICA+ children (group 1) were
      human leukocyte antigen (HLA) typed at the DQ locus along with 123 matched (group
      2) and 235 random (group 3) control subjects (from the original cohort of 3,992).
      Of the ICA+ children, 28 underwent beta-cell function (beta-CF) studies. High
      risk DQ types were surprisingly prevalent in all groups with 35.8% of random
      control subjects carrying DQB1*0302 and 8.9% carrying the highest risk HLA type
      for IDDM, DQB1*0302/*0201. Those individuals with higher ICA titer (> 19 Juvenile
      Diabetes Foundation units [JDF U]) had a significantly higher prevalence of
      DQB1*0302 than those with lower titer ICA or normal control subjects. Six of 7
      individual positive for both ICA and IAA and typed at the DQ locus were
      DQB1*0302/*0201 heterozygotes or DQB1*0302 or DQB1*0201 homozygotes, representing
      three of the highest risk genotypes for IDDM. No correlation was observed between
      ICA titer or DQ type and beta-CF except that all those with beta-CF below the 5th
      percentile carried either DQB1*0302 or DQB1*0201. Prospective follow-up is
      underway to determine if any combination of DQ type and immune markers predicts
      decline in beta-CF and the development of IDDM.

PMID- 8262323
TI  - Effects of chronic vanadate administration in the STZ-induced diabetic rat. The
      antihyperglycemic action of vanadate is attributable entirely to its suppression
      of feeding.
AB  - Vanadate treatment can lower glycemia in diabetic rats. This action is generally
      attributed to vanadate's insulinomimetic properties, but vanadate also inhibits
      feeding, which could lower blood glucose. We therefore assessed the contribution
      of hypophagia to vanadate's antihyperglycemic action in a 3-week study of
      streptozocin-induced (STZ) diabetic rats. Untreated diabetic rats (n = 8) ate 54%
      more food than nondiabetic control rats (P < 0.001). Diabetic rats given sodium
      metavanadate (0.5 mg in 0.5 ml of water by gavage twice daily; n = 8) had
      significantly lower food intakes (P < 0.001) than untreated diabetic rats. In
      vanadate-treated diabetic rats, blood glucose levels were significantly lower
      than in untreated diabetic rats (P < 0.001). Untreated diabetic rats pair-fed to
      the food intake of the vanadate-treated diabetic rats (n = 8) showed virtually
      identical blood glucose falls (P > 0.05 vs. vanadate-treated diabetic rats).
      Vanadate treatment did not affect plasma insulin concentrations in diabetic rats.
      In nondiabetic rats (n = 8), vanadate treatment significantly reduced food intake
      (P < 0.05) and also lowered plasma insulin concentrations (P < 0.05) without
      significantly affecting glycemia. To investigate the mechanism of vanadate's
      hypophagic effect, we also measured regional hypothalamic levels of neuropeptide
      Y (NPY), a potent central appetite stimulant that is thought to drive hyperphagia
      in STZ-induced diabetes. Hypothalamic NPY concentrations rise markedly in
      diabetes and are normalized by insulin replacement. Unlike insulin, vanadate
      treatment did not normalize regional hypothalamic NPY concentrations in diabetic
      rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262325
TI  - Publish or perish.

PMID- 8262324
TI  - Synthesis of type VI collagen by cultured glomerular cells and comparison of its
      regulation by glucose and other factors with that of type IV collagen.
AB  - Homogeneous cultures of calf glomerular mesangial and endothelial cells were
      found to be active in the synthesis of type VI as well as type IV collagen in
      contrast to the epithelial cells that were devoted primarily to the production of
      the latter collagen. Studies with rat mesangial cells indicated that they
      responded to high glucose (20 mM) in the medium by a significant (P < 0.001)
      increase in type VI collagen synthesis as measured by the production of the
      protein and its mRNA level, both of which were closely correlated to each other
      and to glucose consumption. Similar observations were made with type IV collagen,
      but the enhanced formation of this protein was not as rapidly apparent as that of
      type VI and, moreover, could not be as readily reversed on restoration of the
      glucose to a physiological level (5 mM). Evaluation of a number of other agents
      indicated that although mannitol had no effect, L-glucose and NaCl significantly
      stimulated synthesis of both type VI and IV collagens and glucose consumption.
      Insulin-like growth factor I and aldosterone, on the other hand, also increased
      glucose consumption but brought about an enhancement of only type IV collagen
      production, suggesting that the two collagens are independently regulated. This
      possibility was supported by our observation that pyruvate, which was actively
      taken up by the cells, selectively stimulated type IV collagen
      production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262326
TI  - Economic impact of applications of monoclonal antibodies to medicine and biology.

PMID- 8262327
TI  - Evaluation of the safety issue of mercury release from dental fillings.

PMID- 8262328
TI  - Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and
      metastasis.
AB  - Tumor invasion and metastasis formation are major obstacles for successful cancer
      therapy. Metastasis is a complex multistep process that requires sequential
      interactions between the invasive cell and the extracellular matrix. A model
      system for tumor invasion of extracellular matrix barriers has been developed,
      and application of this model has facilitated our understanding of the molecular
      mechanisms of metastasis formation. This model consists of three steps: tumor
      cell adhesion, extracellular matrix proteolysis, and cell migration. The role of
      the matrix metalloprotease enzymes in tumor cell-mediated extracellular matrix
      proteolysis is well established. We review the functional domain structure of the
      matrix metalloprotease enzymes in general and specifically the interaction of
      metastasis-associated gelatinase A (72-kDa type IV collagenase) with the tissue
      inhibitor of metalloproteases-2 (TIMP-2). We also discuss the physiologic
      activation of the matrix metalloprotease enzymes and the specific cellular
      mechanism of action of gelatinase A.

PMID- 8262329
TI  - Aconitase, a two-faced protein: enzyme and iron regulatory factor.
AB  - In this brief survey, the path of development of our knowledge of the iron-sulfur
      enzyme aconitase [citrate(isocitrate)hydrolyase EC4.2.1.3.] is traced from its
      discovery in 1937. Particular emphasis is on developments in the past decade,
      when EPR, Mossbauer and electron nuclear double resonance spectroscopies, X-ray
      crystallography, and mutational analysis were applied to the problem. More
      recently discovered was the significant amino acid sequence identity between
      mitochondrial aconitase and the iron regulatory factor or iron-responsive element
      binding protein (IRE-BP). This has led to the realization that IRE-BP is an
      alternative form of cytosolic (not of mitochondrial) aconitase that is devoid of
      its cubane Fe-S cluster.

PMID- 8262330
TI  - Structural-functional correlates of the nicotinic acetylcholine receptor and its
      lipid microenvironment.
AB  - Among the proteins specialized in signal transduction, the nicotinic
      acetylcholine receptor (AChR) is the best-characterized member of the superfamily
      of ligand-gated ion channels. Since the early finding of a motionally restricted
      shell of lipids (annulus) encircling the protein in its native membrane, there is
      growing experimental evidence supporting the notion that this interface region is
      the locus of a variety of pharmacologically relevant processes, including some of
      the actions of local anesthetics, steroids, and other lipophilic compounds.
      Biochemical data on the composition and metabolism of AChR-rich membranes and
      cells, combined with biophysical data on their structure and dynamics, are
      beginning to provide information on the nature of the annulus itself. Patch-clamp
      data on cells expressing the AChR protein add another dimension to this
      knowledge, enabling correlations to be established between the chemical
      composition of lipid-modified cells and the functional properties of the receptor
      protein in situ at the single-channel level. The effect of free fatty acids,
      alcohols, phospholipids, cholesterol, and steroid glucocorticoid hormones on the
      function of the AChR is reviewed. In the case of steroids, their effects at the
      single-channel level bear a relationship to their use in pathological conditions
      of medical relevance, e.g., in the treatment of the disease myasthenia gravis.

PMID- 8262331
TI  - Hepatic glutaminase expression: relationship to kidney-type glutaminase and to
      the urea cycle.
AB  - Glutamine functions as a major transport form of nitrogen and carbon within the
      body. In the liver, glutamine is hydrolyzed by a unique liver-type, phosphate
      activated glutaminase, and the end products of hepatic glutamine catabolism are
      glucose and urea. Other tissues possess a different, kidney-type, glutaminase
      isozyme. The predicted amino acid sequences for the two glutaminases show a high
      degree of identity, indicating that they are products of different but related
      genes. Hepatic glutaminase activity is increased during diabetes, starvation, and
      on feeding high-protein diets, and decreased on feeding low-protein diets,
      whereas renal glutaminase appears to be regulated only by changes in acid-base
      status. Changes in the rate of gene transcription are the principal mechanism
      responsible for the long-term regulation of hepatic glutaminase, but the renal
      enzyme is regulated at the level of mRNA turnover. The pattern of regulation of
      hepatic glutaminase parallels that seen for genes encoding key enzymes of
      gluconeogenesis and urea synthesis, and indicates coordinate regulation of
      expression in keeping with the role of hepatic glutamine catabolism in these
      pathways.

PMID- 8262332
TI  - Osteopontin: a protein with diverse functions.
AB  - In this review most of the various known, suspected, or postulated functions of
      osteopontin, a secreted highly acidic phosphoprotein, are discussed in terms of
      what we currently know about the protein. These include 1) binding of OPN both to
      cells via a GRGDS cell adhesion sequence that recognizes the alpha v beta 3
      integrin and to extracellular matrix components via poorly characterized motifs,
      2) regulation of the formation and remodeling of mineralized tissue, 3)
      recruiting and stimulating macrophages and lymphocytes as part of a nonspecific
      response to microbial infections, 4) multiple interactions with Ca2+ that likely
      influence OPN protein conformation and may be important in Ca(2+)-mediated or
      Ca(2+)-dependent processes, 5) inhibiting the growth of calcium oxalate crystals
      by disruption of the growing crystal lattice, 6) effects on gene expression, Ca2+
      regulation, and nitric oxide production, and 7) involvement in cell migration.
      OPN production is frequently augmented when cell signaling pathways are activated
      by any of a variety of stimuli, for example in cancer cells.

PMID- 8262333
TI  - Protein-sulfenic acid stabilization and function in enzyme catalysis and gene
      regulation.
AB  - Sulfenic acids (R-SOH) result from the stoichiometric oxidations of thiols with
      mild oxidants such as H2O2; in solution, however, these derivatives accumulate
      only transiently due to rapid self-condensation reactions, further oxidations to
      the sulfinic and/or sulfonic acids, and reactions with nucleophiles such as R-SH.
      In contrast, oxidations of cysteinyl side chains in proteins, where disulfide
      bond formation can be prevented and where the reactivity of the nascent cysteine
      sulfenic acid (Cys-SOH) can be controlled, have previously been shown to yield
      stable active-site Cys-SOH derivatives of papain and glyceraldehyde-3-phosphate
      dehydrogenase. More recently, however, functional Cys-SOH residues have been
      identified in the native oxidized forms of the FAD-containing NADH peroxidase and
      NADH oxidase from Streptococcus faecalis; these two proteins constitute a new
      class within the flavoprotein disulfide reductase family. In addition, Cys-SOH
      derivatives have been suggested to play important roles in redox regulation of
      the DNA-binding activities of transcription factors such as Fos and Jun, OxyR,
      and bovine papillomavirus type 1 E2 protein. Structural inferences for the
      stabilization of protein-sulfenic acids, drawn from the refined 2.16-A structure
      of the streptococcal NADH peroxidase, provide a molecular basis for understanding
      the proposed redox functions of these novel cofactors in both enzyme catalysis
      and transcriptional regulation.

PMID- 8262334
TI  - Noninvasive ultrasound techniques versus angiography for monitoring drug-induced
      changes of the arterial walls.
AB  - Even though angiographic studies contribute to understanding the process of
      atherosclerosis progression/regression in humans, they have several important
      limitations. The number of participants in all the studies is small and those who
      accept the invasive vascular investigation are highly selected patients, in most
      instances in an advanced stage of cardiovascular disease. Furthermore,
      arteriography provides the image of the vessel lumen but no information on the
      vessel wall. Noninvasive methods can describe the characteristics of the arteries
      with regard to morphology (intima-media thickness, surface irregularities, areas
      of calcification) and the hemodynamic correlates of vascular lesions. No single
      methodology describes all aspects of the disease process. However, B-mode
      ultrasound imaging gives information on the vessel wall, whereas Doppler mainly
      describes the hemodynamic consequences of arterial disease. Before any
      noninvasive methodology can be adopted for a clinical trial, extensive validation
      data (preferably using pathology rather than angiography as a "gold standard"),
      and accurate information on reproducibility and on inter-, intraobserver
      variability, should be available. Also, quantitative details on the natural
      history of the disease and on the potential of intervention, as evaluated by the
      specific methodology to be used, should be known.

PMID- 8262335
TI  - Modifications of Ca2+ signaling by inorganic mercury in PC12 cells.
AB  - The effects of different levels of inorganic mercury (Hg2+) on depolarization- or
      agonist-stimulated Ca2+ signals were studied in PC12 cells. Exposure to 50-300 nM
      Hg2+ did not alter the resting cytosolic free Ca2+ concentration ([Ca2+]i), but
      enhanced the Ca2+ response to KCL-induced depolarization. Patch-clamp experiments
      revealed that these Hg2+ concentrations increased the voltage-dependent Ca2+
      current through L-type channels. Also, Hg2+ treatment amplified the intracellular
      [Ca2+]i transients elicited by extracellular ATP. In contrast, the Ca2+ increase
      stimulated by bradykinin was unaffected. At slightly higher concentrations (1 to
      2 microM), Hg2+ caused a sustained rise of the resting [Ca2+]i. This increase did
      not occur in Ca(2+)-free medium and was prevented by pretreatment with NiCl2 or
      with the L-type Ca2+ channel blockers, verapamil and nifedipine. Hg2+ did not
      mobilize Ca2+ from intracellular stores sensitive to thapsigargin, 2,5-di-(tert
      butyl)-benzohydroquinone, or caffeine. At 2 microM, Hg2+ inhibited the [Ca2+]i
      transients elicited by bradykinin, ATP, or KCl-induced depolarization. The loss
      of the intracellular Ca2+ response to bradykinin was independent from the Ca2+
      overload elicit by Hg2+; instead, it was associated with inhibition of
      polyphosphoinositide generation. Exposure to the lower Hg2+ concentrations (0.3
      0.5 microM) greatly potentiated NGF-induced PC12 cell differentiation.
      Conversely, treatment with 2 microM Hg2+ caused cell death. Our results show that
      inorganic mercury has selective and different effects on Ca2+ signaling in PC12
      cells depending on the concentration, within a narrow range.

PMID- 8262337
TI  - What is not taught in dental school.

PMID- 8262336
TI  - P/O ratios--the first fifty years.

PMID- 8262338
TI  - Confidentiality between the dentist and the adolescent, Part II.

PMID- 8262339
TI  - 1992 FDA drug approvals.

PMID- 8262340
TI  - Shortage of qualified dental technicians.

PMID- 8262341
TI  - Treatment of snoring and obstructive sleep apnea with a dental device.

PMID- 8262342
TI  - Fluoride release and shear bond strength of seven base materials.

PMID- 8262343
TI  - Imperative early treatment of anterior open bite.

PMID- 8262344
TI  - Intraoral herpes simplex recurrens associated with a fractured tooth.

PMID- 8262345
TI  - The platform interocclusal registration technique.

PMID- 8262346
TI  - The dentist hangs here: dental images in current art and illustration.

PMID- 8262347
TI  - Improving teamwork with a meeting facilitator.

PMID- 8262348
TI  - Intracanal medication in endodontic treatment: a survey of endodontic programs.

PMID- 8262349
TI  - Patient perceptions of the risk of contracting HIV in the dental office.

PMID- 8262350
TI  - Medical insurance billing.

PMID- 8262351
TI  - Steroidogenesis in Fundulus heteroclitus V.: purification, characterization, and
      metabolism of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one by intact follicles and
      its role in oocyte maturation.
AB  - In vitro steroidogenesis of ovarian follicles incubated with radioactive
      precursors or a Fundulus heteroclitus pituitary extract (FPE) was investigated.
      Steroids were extracted from both the medium and follicular tissue and
      fractionated by liquid or thin-layer chromatography. A similar pattern of steroid
      metabolites was obtained with either [14C]pregnenolone or [14C]progesterone as
      exogenous precursor. Several metabolites comigrated with known reference steroids
      and thus were tentatively identified. Some have been previously reported to
      induce germinal vesicle breakdown (GVBD) in this and other species, particularly
      17 alpha,20 beta-dihydroxy-4-pregnen-3-one (DHP). [3H]DHP added to intact
      follicles or denuded oocytes was also extensively metabolized. All the DHP
      metabolites produced by the intact follicle were tested for biological activity.
      Three of the metabolites were almost as effective inducers of GVBD as DHP itself,
      and two were tentatively identified as 5 alpha-pregnan-3 alpha,17 alpha,20 beta
      triol and 5 alpha-pregnan-3 beta,17 alpha,20 beta-triol. However, DHP was the
      most potent and the quickest inducer of GVBD, indicating that its maturational
      action is not due to metabolic conversion to a more active form. In addition, we
      found two very active fractions after HPLC analysis of steroid extracts from FPE
      stimulated follicles: one that corresponded to and was further identified (mass
      spectroscopy) as DHP and a second tentatively identified as the DHP metabolite 5
      alpha-pregnan-3 beta,17 alpha,20 beta-triol. This study provides strong evidence
      that DHP plays the major role as a maturation inducing-steroid in F.
      heteroclitus, even though DHP is not the only active steroid produced by maturing
      follicles.

PMID- 8262352
TI  - Further studies on the influence of GnRH on the biosynthesis of gonadotropins in
      female frogs (Rana pipiens).
AB  - To further investigate the action of gonadotropin-releasing hormone (GnRH) on
      pituitaries of female frogs (Rana pipiens), gonadotropin (Gth) secretion and
      synthesis was measured following either the in vivo or in vitro exposure to GnRH.
      Treating frogs with a GnRH-agonist (GnRHa) in vivo for either 2 or 5 days led to
      an elevation in plasma Gth compared to that of saline-injected controls. In
      general, the pattern of Gth secretion in vitro paralleled changes observed in
      their plasma levels. GnRHa-treated frogs also had depressed pituitary content of
      Gth as compared to controls. Pituitaries from frogs treated with GnRHa for 5 days
      had higher levels of Gth synthesis than those of controls; however Gth synthesis
      in females treated with GnRHa for only 2 days was not elevated. After 30 hr of
      continuous exposure to 100 ng/ml GnRH in vitro, glands from females secreted
      markedly higher levels of LN and FSH than glands not exposed to the secretagogue.
      The levels of LH and FSH contained within pituitaries exposed to GnRH were
      significantly less than those of control glands. Prolonged exposure to GnRH
      elevated both the secretion of radiolabeled Gth as well as increased the total
      synthesis of Gth (compared to those of controls). These results indicate that
      GnRH can stimulate the biosynthesis of Gth in pituitaries of female frogs;
      however these results differ from those previously obtained with males. It
      appears that female glands require a much longer duration of GnRH stimulation
      than males before Gth synthesis is elevated.

PMID- 8262353
TI  - Metabolism and cardiovascular effects of leukotrienes in the marine toad Bufo
      marinus.
AB  - Leukotriene (LT) metabolism and physiology have been studied extensively in
      mammals; however, little is known of their roles in nonmammalian vertebrates.
      This study examines the cardiovascular effects of leukotrienes on blood pressure
      and heart rate in the conscious and cannulated marine toad, Bufo marinus. The
      sulfidopeptide leukotrienes, LTC4, LTD4, and LTE4 elicited hypotension with equal
      potency. However, with respect to heart rate changes and duration of action, the
      responses to LTC4 and LTD4 were greater and lasted longer than those to LTE4. The
      nonpeptide leukotriene, LTB4, had significantly less potent effects on heart rate
      and blood pressure. The leukotriene-induced increases in heart rate with 1000 and
      300 ng/kg body wt LTC4 and LTD4 were blocked with 5 mg/kg body wt propranolol, a
      beta-antagonist, suggesting sympathetic reflex regulation of heart rate.
      Metabolism of [3H]LTC4 to [3H]LTD4 and [3H]LTE4 occurred rapidly in blood, with
      complete conversion to [3H]LTE4 within 5 min. Conversion was slower in plasma,
      with 18.9 +/- 0.5% of the radioactivity associated with [3H]LTC4 still remaining
      after 120 min. The toad is more similar to mammals than the bullfrog with respect
      to the metabolism of leukotrienes. In contrast to mammals, leukotrienes have
      hypotensive effects in both toad and bullfrog, although the order of potency
      differs. The effectiveness of the sulfidopeptide leukotrienes in eliciting
      hypotension at low doses (1 ng/kg body wt) suggests that these compounds may be
      important cardiovascular regulators in the toad.

PMID- 8262354
TI  - Characterization of putative glomerular receptors for angiotensin II in the
      rainbow trout Oncorhynchus mykiss using the antagonists Losartan, PD 123177, and
      saralasin.
AB  - Isolated glomeruli from the rainbow trout Oncorhynchus mykiss have been examined
      for the presence of receptors specific for angiotensin II (AII). Specific binding
      of 125I-Asp1Val5-AII was saturable, plateaued after 20 min, and increased with
      glomerular protein. Saralasin (Sar1Val5Ala8-AII), a nonselective peptide AII
      receptor antagonist of AII binding to mammalian tissues, was a poor inhibitor of
      125I-Asn1Val5-AII binding to trout glomeruli. However, the nonpeptide antagonist,
      Losartan (= DuP 753), which is specific for AII subtype AT1 receptors in
      mammalian tissues, was an effective inhibitor of binding of both 125I-Asp1Val5
      AII and 125I-Asn1Val5-AII to trout glomeruli. The IC50 for Losartan inhibition of
      binding of Asp1Val5-AII was 1.25 +/- 0.07 x 10(-8) M while that for inhibition of
      binding of Asn1Val5-AII was 2.73 +/- 0.45 x 10(-8) M. Statistical analysis of
      logistic curve fits confirmed the easier displacement of Asp1Val5-AII than of
      Asn1Val5-AII. PD 123177, a nonpeptide antagonist specific for AII subtype AT2
      receptors in mammalian systems, was ineffective as an antagonist of AII binding
      to trout glomeruli. These results are consistent with the presence of a specific
      AII receptor in the trout glomerulus and imply a novel receptor configuration.

PMID- 8262355
TI  - Pituitary of "cobalt" variant of the rainbow trout separated from the
      hypothalamus lacks most pars intermedial and neurohypophysial tissue.
AB  - Adenohypophysial cell types and neurohypophysial tissues were investigated in the
      cobalt variant of the rainbow trout, which possesses an irregularly-shaped
      pituitary. The pituitary remnant was completely detached from the hypothalamus in
      all but one fish, in which a remnant was associated with the hypothalamus.
      Prolactin (PRL) and growth hormone (GH) cells were predominant cell types in all
      pituitary remnants, forming PRL and GH areas, respectively. There were fewer
      somatolactin (SL) and melanophore-stimulating hormone cells than in normal fish.
      There were few corticotropin cells in cobalt and normal trout. Although aldehyde
      fuchsin positive cells were also present, positively-staining fibers were not
      detected in any of remnants examined. Plasma SL levels were much lower in cobalt
      than in normal trout. Plasma levels of GH and T3 were significantly lower in
      cobalt than in normal fish. Plasma levels of PRL, T4 and cortisol, plasma
      osmolality, ions (Na+, K+, Ca2+, and Mg2+), glucose, triglyceride, free fatty
      acids, and amino nitrogen concentrations were similar in the two groups. Cobalt
      variants thus lack hypophysial pars intermedia and neurohypophysial tissues.
      Various abnormalities of the cobalt variant, such as the cobalt blue body color
      and the fat deposition in the abdominal cavity, may be related to the absence of
      the pars intermedia.

PMID- 8262356
TI  - Functional differentiation of the pituitary gland during development of the
      domestic ring dove (Streptopelia roseogrisea).
AB  - The development and differentiation of the anterior pituitary gland was studied
      in the domestic ring dove (Streptopelia roseogrisea) and compared with the
      pattern of body growth. By combining histochemical staining techniques with
      immunohistochemical methods, cells producing prolactin (PRL), growth hormone
      (GH), thyrotropic hormone (TSH), and adrenocorticotropic hormone were identified
      in the pituitary of the developing ring dove. The distribution of the four cell
      types within the anterior pituitary was illustrated by three-dimensional
      reconstruction from immunohistochemically stained serial sections. The pattern,
      which was shown to change through embryonic and juvenile development, was
      described and compared with examples from other vertebrate classes. The analysis
      of body growth showed that the development of the nestlings could be divided into
      two distinct growth phases. The first seven days were characterized by a
      consistently high rate of body growth, whereas after Day seven the growth rate
      was markedly reduced. Although GH-immunoreactive cells formed the dominant cell
      type in the pituitary during the whole postembryonic development, there was no
      correlation between the rate of body growth and the abundance of GH
      immunoreactive cells in the pituitary. In contrast, changes in the abundance of
      PRL- and TSH-immunoreactive cells were observed simultaneously with the
      transition from the first to the second growth phase. The proportion of PRL
      immunoreactive cells was relatively high during the first seven days, whereas TSH
      immunoreactive cells became more abundant during the second growth phase. It is
      therefore postulated that PRL and TSH play an important role in the regulation of
      the growth pattern in the ring dove.

PMID- 8262357
TI  - Sensitive stages for the effects of temperature on gonadal aromatase activity in
      embryos of the marine turtle Dermochelys coriacea.
AB  - Many data suggest an involvement of estrogens in gonadal differentiation in
      reptiles with temperature-dependent sex determination (TSD). However, the site of
      estrogen synthesis in two species of freshwater turtles is unclear. In Emys
      orbicularis, estrogens were shown to be produced by the gonads, whereas in
      Trachemys scripta, gonadal steroids were not detected. The marine turtle
      Dermochelys coriacea exhibits TSD but in gonadal development, ovarian
      differentiation is delayed. Gonadal aromatase activity and estrogen content in
      this species were measured in embryos incubated at 27 degrees and in embryos
      incubated at 30.5 degrees, respectively, masculinizing and feminizing
      temperatures within the range of temperatures found in natural nests. At all
      stages studied, aromatase activity was present and found to be higher at 30.5
      degrees than at 27 degrees. Estrogens were only found at 30.5 degrees. The
      effects of temperature shifts on gonadal aromatase activity were then examined.
      Eggs were shifted from 27 to 35 degrees (feminizing temperature) at different
      embryonic stages and exposed to 35 degrees for 6 days. An increase in gonadal
      aromatase activity, although with significant individual variations, was seen
      only when eggs were shifted between stages 23 and 27. These stages are in the
      range of the thermosensitive stages for sexual differentiation of the gonads
      determined in other turtles. These results are similar to those previously
      obtained in E. orbicularis and agree with a key role for endogenous estrogens in
      gonadal differentiation of reptiles with TSD.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262358
TI  - A comparative study of annual changes in the pineal gland morphology with
      reference to the influence of melatonin on testicular activity in tropical birds,
      Psittacula cyanocephala and Ploceus philippinus.
AB  - The aim of the present comparative investigation was to examine annual pineal
      cytological changes and the action of melatonin in relation to testicular
      activity in two wild tropical avian species. The findings revealed that in both
      blossomheaded parakeets (Psittacula cyanocephala) and Indian weaver birds
      (Ploceus philippinus) the pineal gland was inactive, with reduced karyometric
      values during the breeding season. A pinealoactive phase showing significantly
      increased pinealocyte nuclear diameter corresponded with the nonbreeding phase.
      Administration of melatonin (250 micrograms/100 g body wt) for 10 consecutive
      days caused significant involution of testes during the breeding phase, although
      it failed to alter reproductive activity during the nonbreeding phase. The
      results indicated that the pineal gland activity varied inversely with the
      seasonal testicular weight cycle and the antigonadal influence of melatonin
      appeared to be phase dependent, which corroborated the inverse temporal
      relationship of the pineal gland and male reproductive activity examined in the
      two tropical avian species.

PMID- 8262359
TI  - Morphological changes in the thecal layer during the maturation of the
      preovulatory ovarian follicle of the domestic fowl (Gallus domesticus).
AB  - The aim of the present study was to evaluate changes in the steroidogenic tissue,
      the blood vessels and the undifferentiated cell islets observed in the theca of
      developing follicles in the hen ovary. Samples of preovulatory follicles (F1 to
      F5 in order of decreasing size) and small yellow follicles (SYF) were obtained
      from White Leghorn hens for light microscopy studies. Cell suspensions of the
      whole theca obtained from follicles at the same stage of development were
      analyzed for 17 beta-estradiol and testosterone secretion. Typical steroidogenic
      cells with abundant cytoplasmic lipid droplets were identified in the theca
      interna beside blood vessels and nerve fibers. Islets of undifferentiated cells
      were observed in the theca externa. The steroidogenic tissue of the theca interna
      was evident in the small yellow follicle. However, considering the growth of the
      developing follicle, the total volume of steroidogenic cells increased from the
      SYF up to F1 follicle. The blood vessels reached the maximum development in the
      largest follicle (F1). On the other hand, undifferentiated cell islets were
      markedly reduced in the F1 follicle. The structural changes herein described
      could be correlated to modifications in the steroid hormone secretion during the
      maturation of the ovarian follicle.

PMID- 8262360
TI  - CCK/gastrin-like immunoreactivity in the goldfish pituitary: regulation of
      pituitary hormone secretion by CCK-like peptides in vitro.
AB  - The presence and distribution of cholecystokinin (CCK)/gastrin-like
      immunoreactivity (IR) was examined in the goldfish pituitary. Intense CCK/gastrin
      like IR was consistently observed within fibers of the proximal pars distalis
      (PD), with fewer IR fibers localized in the rostral PD. Within the proximal PD
      CCK/gastrin-like IR fibers were distributed among both the gonadotrophs and
      somatotrophs, suggesting a possible role for CCK-like peptides in the regulation
      of gonadotropin-II (GtH-II) and growth hormone (GH) secretion. Exposure of
      pituitary fragments from either sexually gonadal recrudescing (maturing) or
      regressed goldfish to three 5-min pulses of 1.0 or 10 nM sulfated CCK8 (CCK8-s),
      at 55-min interpulse intervals, resulted in an increased secretion of both GtH-II
      and GH. Independent of the dose perifused, the GtH-II release responses to the
      second and third pulses of CCK8-s were always of similar magnitude to the first
      pulse at a given dose. For GH, repeated challenges of pituitary fragments to 0.1
      or 1.0 nM CCK8-s stimulated release responses of similar magnitude; however,
      successive pulses of 10 nM CCK8-s resulted in a desensitization in the GH release
      response to the second or the third pulse. Fragments from sexually regressed
      goldfish exhibited an overall greater release response of GtH-II to CCK8-s
      relative to fragments from sexually recrudescing fish, whereas the GH release
      responses to CCK8-s were similar between the two sexual stages. A dose-dependent
      release of GtH-II was present in pituitary fragments from sexually regressed
      goldfish following five 5-min pulses of increasing (0.1 to 100 nM) doses of CCK8
      s. Finally, the sulfated forms of CCK8 and gastrin 17 (G17-s) exhibited greater
      stimulatory abilities than the nonsulfated form of CCK8 in releasing GtH-II and
      GH from fragments of sexually recrudescing fish. Additionally, CCK8-s and G17-s
      were equal in their capacity to stimulate the release of GtH-II, whereas G17-s
      was slightly more effective than CCK8-s in stimulating the release of GH.
      Overall, these studies are the first to provide evidence that IR CCK/gastrin-like
      fibers are codistributed among the gonadotrophs and somatotrophs, and that CCK
      like peptides are highly effective in stimulating GtH-II and GH release from the
      goldfish pituitary.

PMID- 8262361
TI  - SruI restriction endonuclease from Selenomonas ruminantium.
AB  - SruI, specific restriction endonuclease, has been characterized from Selenomonas
      ruminantium isolated from the rumen of fallow deer. Results from the study
      demonstrate that S. ruminantium 18D possesses a type II restriction endonuclease,
      which recognizes the sequence 5'-TTT decreases AAA-3'. The recognition sequence
      of SruI was identified using digestions on pBR322, pBR328, pUC18, M13mp18RF,
      pACYC184 and lambda DNA. The cleavage patterns obtained were compared with
      computer-derived data. SruI recognises the palindromic hexanucleotide sequence
      and cleaves DNA after the third T in the sequence, producing blunt ends. The
      purification and characterization of restriction endonuclease SruI presented here
      is the first described for Selenomonas ruminantium spp. and demonstrates that
      this microorganism possesses a DNA-cleaving enzyme with the same specificity as
      DraI or AhaIII.

PMID- 8262362
TI  - Purification and partial characterization of a lysine-specific protease of
      Porphyromonas gingivalis.
AB  - A lysine-specific protease hydrolysing peptide bonds at the carboxyl side of
      lysine residues in Porphyromonas gingivalis was purified from culture supernatant
      by a combination of ion-exchange chromatography, gel filtration, and affinity
      chromatography. The molecular mass was 48 kDa and the pI value was 7.3. The
      enzyme hydrolysed the peptide bonds at the carboxyl side of lysine residues in
      synthetic substrates and natural proteins.

PMID- 8262363
TI  - Detection of Legionella pneumophila in biofilms containing a complex microbial
      consortium by gas chromatography-mass spectrometry analysis of genus-specific
      hydroxy fatty acids.
AB  - A gas chromatographic-mass spectrometric method was used to detect Legionella
      pneumophila in biofilms in potable water containing a complex microbial
      consortium. The unique 3-hydroxy and 2,3-dihydroxy fatty acids of the L.
      pneumophila lipopolysaccharides (LPS) were detected in both the planktonic phase
      of the continuous culture model and in the biofilms forming on both copper and
      polyethylene substrata. The technique confirmed that lower numbers of Legionella
      colonised and grew on copper in comparison to polyethylene and offers promise for
      routine detection of Legionella in biofilms in the environment.

PMID- 8262364
TI  - Anomalous growth of Staphylococcus epidermidis in the presence of Silastic and
      glycopeptide antibiotics.
AB  - In the presence of supra-inhibitory concentrations of the glycopeptide
      antibiotics vancomycin and teicoplanin, biofilms of Staphylococcus epidermidis on
      a Silastic surface produce anomalous growth. This takes the form of macroscopic,
      cohesive aggregates of cocci bound together with slime. This phenomenon was
      intermittent, independent of antibiotic concentrations between 20 and 50
      micrograms ml-1, occurred more often with teicoplanin, and was found both with
      slime-positive and slime-negative strains.

PMID- 8262365
TI  - A DNA module encoding bph genes for the degradation of polychlorinated biphenyls
      (PCBs).
AB  - In this report we describe the development and construction of a DNA module which
      encodes bph genes for the metabolism of PCBs and which is capable of stable
      integration into the chromosome of Gram negative bacteria. Introduction of the
      bph-module into Pseudomonas putida KT2442, Pseudomonas sp. strain B13 and its
      genetically engineered derivative B13FR1 expanded the biodegradative ability of
      these strains to include biphenyl and 4-chlorobiphenyl. The bph operon was stably
      inherited under laboratory conditions. Behavior of the genetically engineered
      strains was evaluated under simulated natural habitat conditions in lake sediment
      microcosms with respect to survival and removal of 4-chlorobiphenyl. The
      genetically engineered strains persisted under these conditions and were
      effective in degrading 4-chlorobiphenyl over a five day incubation period.

PMID- 8262366
TI  - Cell vacuolization induced by Helicobacter pylori: inhibition by bafilomycins A1,
      B1, C1 and D.
AB  - All available bafilomycins (A1, B1, C1 and D) inhibit and revert macroscopic
      vacuolization induced by Helicobacter pylori cell-free extracts. Bafilomycin A1
      displays the highest activity, followed by bafilomycin B1, C1 and D. The
      different potency of bafilomycins correlates with their ability to inhibit the
      vacuolar-type ATPase (V-ATPase) and to dissipate the membrane pH gradient of
      intracellular acidic organelles. These results suggest that bafilomycins should
      be considered as possible therapeutic agents in the treatment of gastritis.

PMID- 8262367
TI  - Presumptive identification of common adenovirus serotypes by the development of
      differential cytopathic effects in the human lung carcinoma (A549) cell culture.
AB  - The neutralization test is commonly used in clinical virology laboratories for
      the identification by serotype of adenovirus isolates. In an effort to conserve
      reagents and reduce the amount of time in the performance of this assay, we
      evaluated the significance of differential cytopathic effects for the presumptive
      identification of lower-numbered adenovirus serotypes that are commonly
      encountered in the clinical setting. Utilizing the human lung carcinoma (A549)
      cell culture as our indicator system, two viral induced monolayer degenerations
      (i.e., cytopathic effects or CPEs) were recognized. Among our wild and the
      laboratory adapted (i.e., ATCC) adenovirus isolates tested in this study,
      serotypes 1, 2, 4, 5, 6, 8, 11, 19, 21, 27, and 31 were expectedly characterized
      by the typically enlarged, rounded, and refractile cells, which eventually
      aggregated into irregular 'grape-like' clusters. Adenovirus types 3 and 7,
      however, were characterized by the development of distinct intranuclear
      inclusions, a flattening and then a web or net-like monolayer degeneration.
      Differences in the intensity of intranuclear granulation were related by electron
      microscopy to differences in the quantity of viral crystalline aggregates within
      the host cell nucleus. A presumptive identification of the commonly encountered
      adenovirus serotypes 3 and 7 prior to the performance of the neutralization test
      would result in a conservation of type-specific antiserum, a decreased use of
      cell cultures and medium, and lastly, reduced medical technologist workload.

PMID- 8262368
TI  - Induction of cadmium tolerance in Escherichia coli K-12.
AB  - Cadmium ions are bacteriocidal, resulting in exponential killing that starts
      immediately after exposure. We have shown that pretreatment with sublethal
      concentrations of cadmium induces cadmium tolerance. Protection against cadmium
      killing can also be obtained by preincubation at elevated temperatures, known to
      induce the heat-shock response. However, in contrast to pretreatment at elevated
      temperatures, exposure to sublethal cadmium concentrations does not induce
      thermotolerance.

PMID- 8262369
TI  - Inducible resistance to zinc ions in Bacillus subtilis 168.
AB  - Chromosomally determined resistance to Zn2+ ions is a property of Bacillus
      subtilis 168. Resistance is inducible and is not connected with Cd2+ resistance,
      characteristic of plasmid determined resistance in bacteria. A few proteins were
      shown to respond to inducible levels of the cation.

PMID- 8262370
TI  - Activation of FNR-dependent transcription by iron: an in vitro switch for FNR.
AB  - FNR is an iron-binding transcriptional regulator of Escherichia coli which
      controls the expression of target genes in response to anaerobiosis. The
      mechanism used by FNR to sense and respond to anaerobiosis is unknown but it is
      thought to involve iron. In vitro transcription analyses have shown that iron
      deficient FNR is unable to activate transcription from the FF-melR promoter, but
      activity could be restored by preincubation with Fe2+ and beta-mercaptoethanol.
      The reactivation of FNR was prevented and reversed by chelating agents, and this
      reactivation thus provides an artificial in vitro switch for FNR-dependent
      transcriptional activation.

PMID- 8262371
TI  - Multiple oral inoculations with Cryptosporidium parvum as a means of immunization
      for production of monoclonal antibodies.
AB  - Oral immunization of suckling mice with Cryptosporidium parvum results in a
      humoral response to a limited set of antigens. Six-day-old BALB/c mice were each
      inoculated orally with 1 x 10(6) viable oocysts and subsequently administered
      oral inoculations of 2 x 10(6) viable oocysts at 30 and 60 days following the
      primary infection. After 45 days, mice were boosted with 1 x 10(6) oocysts
      orally, plus soluble extracts equivalent to 2 x 10(6) and 1 x 10(6) oocysts given
      intravenously and intraperitoneally, respectively. Four days later, splenic
      lymphocytes were fused to Ag8 myeloma cells. Using this method, we have been able
      to select for monoclonal antibodies that predominantly recognize sporozoite
      surface and apical complex antigens.

PMID- 8262372
TI  - Mutants of the two-component regulatory protein FixJ of Rhizobium meliloti that
      have increased activity at the nifA promoter.
AB  - FixL and FixJ belong to a two-component regulatory system in Rhizobium meliloti
      that induces the expression of numerous nitrogen-fixation genes during symbiosis
      with alfalfa. FixJ is a positive activator required for transcription of the
      regulatory genes nifA and fixK, while FixL is an oxygen-binding hemoprotein
      capable of regulating the phosphorylation status of both itself and FixJ, in
      response to oxygen availability. In this study, we isolated four FixJ mutants
      that display increased activity at the nifA promoter (PnifA) in Escherichia coli.
      All four mutants possess amino acid changes in a domain of FixJ that is conserved
      in other response regulator proteins, and all exhibit increased activity at PnifA
      in R. meliloti that is dependent on the presence of FixL. One of the mutant
      proteins, while less efficient at accepting phosphate from a truncated derivative
      of FixL (FixL*), nevertheless has a phosphorylated form that is more stable than
      the phosphorylated form of wild-type (wt) FixJ and is more resistant to the
      phosphatase activity of FixL*. The wt FixJ-phosphate was found to have a half
      life of approximately 4 h, which makes it an unusually long-lived response
      regulator protein. The exceptional stability of wt FixJ-phosphate and the altered
      phosphorylation properties observed for the mutant are discussed in relation to
      signal transduction in the FixLJ system.

PMID- 8262373
TI  - SIRE-1, a long interspersed repetitive DNA element from soybean with weak
      sequence similarity to retrotransposons: initial characterization and partial
      sequence.
AB  - Gm776 is a 776-bp subregion of a member of an interspersed family of relatively
      homogeneous repetitive DNA elements from soybean (Glycine max). The fragment was
      originally amplified from soybean DNA by the polymerase chain reaction using a
      single 22-nucleotide primer, and consequently terminates in an inverted repeat.
      The elements defined by Gm776 are at least 10.6 kb in length and constitute a
      family of 500-800 members per haploid genome. The family has been designated SIRE
      1 (soybean interspersed repetitive element 1). Overlapping regions of Gm776
      exhibit suggestive DNA sequence similarity to Ta1 and Ty1, copia-like
      retrotransposons from Arabidopsis thaliana and Saccharomyces cerevisiae,
      respectively. However, there are no similarities at the amino acid level, and the
      regions of similarity are not functionally related.

PMID- 8262374
TI  - Two putative African swine fever virus helicases similar to yeast 'DEAH' pre-mRNA
      processing proteins and vaccinia virus ATPases D11L and D6R.
AB  - Two open reading frames (ORFs) of African swine fever virus (ASFV) encoding
      putative helicases have been sequenced. The two genes, termed D1133L and B962L,
      are located in the central region of the viral genome, but are separated by about
      40 kb of DNA. Both genes are expressed late during ASFV infection of Vero cells,
      after replication of viral DNA has begun. Contiguous to D1133L, three other ORFs
      (D129L, D79L and D339L), encoding putative proteins of unknown function, have
      been sequenced. Proteins D1133L and B962L contain the amino acid motifs that
      characterize helicases of superfamily II. D1133L is most similar to a group of
      putative helicases which includes two proteins of vaccinia virus (D11L and D6R)
      involved in transcription of the viral genome, their homologues in other
      poxviruses, the protein encoded by ORF 4 of the yeast plasmids, pGKL2 and pSKL,
      and the previously identified ASFV protein, Q706L. B962L resembles a group of RNA
      helicase-like proteins which includes three proteins of Saccharomyces cerevisiae
      involved in pre-mRNA splicing (PRP2, PRP16 and PRP22), Drosophila melanogaster
      KURZ and MLE, and vaccinia virus 18R.

PMID- 8262375
TI  - A molecular and cytogenetic analysis of lambda 20p7 fragment DNA from the
      proximal beta-heterochromatin of Drosophila melanogaster.
AB  - A DNA fragment from the Drosophila melanogaster genome, cloned in lambda 20p7,
      was derived independently from clones lambda 20 and lambda L [Baiborodin et al.,
      Genetika 29 (1993) 403-416; Sharakhov et al., Genetika 29 (1993) 392-402]. In
      situ hybridization of lambda 20p7 DNA to the chromosomes of D. melanogaster
      demonstrated preferential hybridization of the fragment to the chromocenter of
      polytene chromosomes and to pericentric heterochromatin of chromosomes II, IV and
      X at the metaphase plate. Copy number per haploid genome for lambda 20p7 was
      estimated as approximately 200. Based on Southern blotting, the major portion of
      this moderate repeat was localized in the region of a 5.5-kb HindIII digest. In
      situ hybridization to polytene chromosomes from strain fs(2)B trophocytes
      revealed that repeats homologous to lambda 20p7 are located in the proximal
      heterochromatin which undergoes structural reorganization during tissue
      differentiation. The nucleotide sequence of two segments of the clone lambda
      20p7, Dm0.9 and Dm270, was determined. Sequence analysis of the 300-bp Dm0.9
      clone revealed that it contains 21-bp and 30-bp d(GT/CA) sequences, a 12-bp AT
      box, recognition sites for nuclear factors NFI and SpI, and a set of inverted
      repeats. Clone Dm270 contains an open reading frame (ORF). The deduced amino acid
      (aa) sequence shares homology with the gag-like gene from type-I (R1) ribosomal
      DNA insertion and may code for a polypeptide of 10 kDa. The Dm270 sequence was
      found to contain two direct repeats showing homology to the human CENP-B box.

PMID- 8262376
TI  - Differential transcription of multiple copies of a silk worm gene encoding
      tRNA(Gly1).
AB  - Ten different tRNA(Gly1) genes from the silk worm, Bombyx mori, have been cloned
      and characterized. These genes were transcribed in vitro in homologous nuclear
      extracts from the posterior silk gland (PSG) or nuclear extracts derived from the
      middle silk gland or ovarian tissues. Although the transcription levels were much
      higher in the PSG nuclear extracts, the transcriptional efficiency of the
      individual genes followed a similar pattern in all the extracts. Based on the
      levels of in vitro transcription, the ten tRNA(Gly1) genes could be divided into
      three groups, viz., those which were transcribed at very high levels (e.g., clone
      pR8), high to medium levels (e.g., pBmi1, pBmp1, pBmh1, pBmt1) and low to barely
      detectable levels (e.g., pBms1, pBmj1 and pBmk1). The coding sequences of all
      these tRNA genes being identical, the differential transcription suggested that
      the flanking sequences modulate their transcriptional efficiency. The presence of
      positive and negative regulatory elements in the 5' flanking regions of these
      genes was confirmed by transcription competition experiments. A positive element
      was present in the immediate upstream A+T-rich sequences in all the genes, but no
      consensus sequences correlating to the transcriptional status could be generated.
      The presence of negative elements on the other hand was indicated only in some of
      the genes and therefore may have a role in the differential transcription of
      these tRNA(Gly1) genes in vivo.

PMID- 8262377
TI  - Cloning of a mouse cDNA encoding DNA polymerase delta: refinement of the homology
      boxes.
AB  - A mouse DNA polymerase delta (Pol delta)-encoding cDNA (pol delta) was isolated
      by PCR amplification and cDNA library screening. The sequenced cDNA has a length
      of 3386 bp and the open reading frame (ORF) encodes a protein of 1105 amino acids
      (aa) with an M(r) of 123,743. The aa identity to the proteins encoded by the
      corresponding cDNA from Bos taurus (93%) and Homo sapiens (92%) is very high. The
      identity to the Pol delta from Schizosaccharomyces pombe, Saccharomyces
      cerevisiae and Plasmodium falciparum is around 50%. An aa comparison between all
      available Pol delta sequences reveals several common structural motifs.
      Polyclonal antibodies raised against a 31-aa synthetic peptide deduced from the
      ORF specifically recognize Pol delta polymerases from human cells and calf thymus
      in an immunoblot.

PMID- 8262379
TI  - Cloning and partial characterization of the promoter for the human p55 tumor
      necrosis factor (TNF) receptor.
AB  - An 809-bp region at the 5' flank of the human p55 tumor necrosis factor receptor
      (TNF-R)-encoding gene was found to be active in driving expression of the cat
      reporter gene, indicating that it contains a functional promoter. Deletion
      analysis showed that the promoter activity is present in the region between
      nucleotides (nt) -385 and -207; the sequence upstream from this region (nt -809
      to -385) has an inhibitory effect. The promoter for the p55 TNF-R resembles
      housekeeping-type promoters in that it drives transcription from multiple start
      points (tsp) and lacks canonical TATA and CAAT box motifs. The cluster of tsp
      lies in a region which is particularly C+T rich. In this region, upstream from
      and near to the furthest upstream tsp, two closely located TCC repeat motifs were
      identified. These motifs also appear twice in the promoter for the epidermal
      growth factor receptor, where they were shown to be essential for promoter
      activity. The human p55 TNF-R promoter shows an overall resemblance, yet also
      some marked dissimilarities, to the recently described promoter for the mouse p55
      TNF-R.

PMID- 8262378
TI  - Southwestern blot mapping of potential regulatory proteins binding to the DNA
      encoding plasminogen activator inhibitor type 2.
AB  - In order to investigate the molecular basis for the regulated expression of
      plasminogen activator inhibitor type 2 (PAI-2), we sought to identify monocyte
      derived nuclear factors which interact with the PAI-2 gene. We have explored the
      application of Southwestern blot mapping as an approach for identifying specific
      DNA-protein interactions and targeting potential regulatory DNA elements. The
      procedure involves an initial global screening of a crude preparation of nuclear
      proteins with radiolabelled DNA fragments (200-300 bp) derived from a large
      region (8.8 kb) of PAI-2. The bound DNA fragments are eluted and their location
      within PAI-2 mapped by Southern blot hybridization analysis. We have used this
      procedure to examine the differential binding of nuclear factors from the U937
      monocytic cell in the absence and in the presence of the differentiating agent,
      12-phorbol 13-myristate acetate (PMA), in order to identify proteins that bind
      specifically to the 5' flanking promoter region and first intron of PAI-2. Eleven
      DNA-binding proteins ranging in molecular mass from 27 to 92 kDa were identified,
      and the results define three regions of the gene which contain DNA-binding sites
      which may be involved in the transcriptional regulation of PAI-2. Deletion
      analysis using a series of 5' deletion mutants spanning PAI-2 fused to a
      chloramphenicol acetyltransferase-encoding reporter gene (cat) demonstrates that
      two of the regions identified by Southwestern blot mapping contain elements which
      can function to modulate PAI-2 expression in transient transfections of U937
      cells.

PMID- 8262380
TI  - Isolation and characterization of a gene involved in ethylene biosynthesis from
      Arabidopsis thaliana.
AB  - The ethylene forming enzyme (EFE) is a key factor in ethylene biosynthesis. To
      understand better the regulation of ethylene biosynthesis in vegetative tissues,
      we set out to isolate and characterize a complementary DNA (cDNA) encoding the
      EFE from Arabidopsis thaliana. An A. thaliana cDNA library was screened with pTOM
      13, a tomato cDNA coding for the EFE. A cDNA clone (pEAT1) was isolated. The cDNA
      is 1200 nucleotides (nt) in length and predicts a protein of M(r) 36,663. The
      insert includes the complete open reading frame of 972 bp and shows strong
      homology with several reported sequences, both at the nt and amino acid level. In
      whole seedlings, expression of pEAT1 was enhanced by wounding, ethrel, Fe2+, and
      1-amino-cyclopropane-carboxylic acid (ACC) treatments. In contrast, heat shock
      had no effect on the expression.

PMID- 8262381
TI  - Characterisation of potato (Solanum tuberosum L.) extensins: a novel extensin
      like cDNA from dormant tubers.
AB  - A cDNA library from dormant potato tubers was screened for extensin (Ext)-like
      cDNAs (PTEL). The cDNAs recovered were partially sequenced and could be divided
      into two classes. One class, containing the repeating amino acid (aa) motifs,
      SPPPPSPKYVYK and SPPPPSPSPPPPYYYK, constitutes the potato counterpart of the
      tomato Ext-encoding gene previously isolated by Zhou et al. [Plant Mol. Biol. 20
      (1992) 5-17]. A full-length cDNA from the second class was fully sequenced. The
      product of this cDNA has the repetitive sequence and proline-rich composition
      typical of Ext. Features worthy of note are the signal peptide sequence, which
      shares close homology with signal sequences of a number of Ext of diverse origin,
      and the presence of a novel, histidine-rich motif (SPPPHHHHPVYK) repeated within
      the sequence. Wounding of the potato tuber causes a marked increase in Ext-like
      mRNAs, although the species induced are not those present in dormant tissue.

PMID- 8262382
TI  - Cloning of a cDNA encoding a group-V (group-IX) allergen isoform from rye-grass
      pollen that demonstrates specific antigenic immunoreactivity.
AB  - We have isolated and characterized the cDNA clone, 19R, that encodes an isoform
      of a major rye-grass pollen allergen, Lol p V [previously referred to as Lol p
      1b; Singh et al., Proc. Natl. Acad. Sci. USA 88 (1991) 1384-1388; and Lol p IX;
      Suphioglu et al., Lancet 339 (1992) 569-572]. Clone 19R was isolated from a rye
      grass pollen cDNA expression library using grass pollen-specific immunoglobulin E
      (IgE) antibodies (Ab) from an allergic serum pool. The nucleotide (nt) sequence
      of clone 19R potentially encodes a 33.8-kDa protein of 339 amino acids (aa). It
      possesses a leader peptide essentially identical to the previously characterized
      isoform of Lol p V (Lol p VA). This indicates a mature processed 31.3-kDa protein
      of 314 aa, correlating well with the size of the polypeptides revealed by Western
      analysis of pollen proteins using IgE Ab affinity purified from recombinant
      fusion protein (reFP) encoded by clone 19R as solid matrix. There is no N
      glycosylation motif. The protein encoded by clone 19R, designated Lol p VB, has
      66.4% identity and 80.4% similarity with Lol p VA. However, a Lol p VA-specific
      monoclonal Ab, FMC A7, does not recognize reFP encoded by clone 19R, indicating
      that Lol p VB does not share this epitope. Cross-reactivity studies using
      affinity purified IgE Ab showed that both isoforms share similar allergenic
      epitopes. Immunoblot analysis using sera from a population of 30 patients showed
      that 80% possess IgE Ab that recognize both Lol p V isoforms. Variation occurred
      in the signal intensities of IgE binding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262383
TI  - Genomic structure of the Xenopus laevis liver transcription factor LFB1.
AB  - Liver factor B1 [LFB1, also called hepatocyte nuclear factor 1 (HNF1)] is a
      tissue-specific vertebrate transcription factor that is present in the liver,
      intestine, stomach and kidney. The LFB1 protein contains an unusual homeobox that
      is characterized by an insertion of 21 amino acids (aa) not found in any other
      homeodomain protein. We have isolated and characterized the genomic sequences
      encoding the LFB1 of Xenopus laevis. By comparing the genomic sequences with the
      cDNA clones, we could identify nine exons. In general, the position of the
      introns is identical to the one previously found in the rat. However, the C
      terminal activation domain of LFB1 contains, in each species, an exon that is
      split in two in the other species. The homeobox of the X. laevis LFB1 contains an
      intron at exactly the position where the 21 aa typical for LFB1 are inserted.
      This is in agreement with the structure found in the rat gene and supports the
      notion that the LFB1 homeobox evolved separately from the other genes encoding
      homeodomain proteins.

PMID- 8262384
TI  - Cloning and expression of cDNA encoding Xenopus laevis bone morphogenetic protein
      1 during early embryonic development.
AB  - The Xenopus laevis DNA fragment encoding a protein homologous with human bone
      morphogenetic protein-1 (BMP-1) was amplified by polymerase chain reaction (PCR)
      from cDNA derived from stage 26 (st.26) embryonic RNA. Subsequently this fragment
      was used as a probe to isolate cDNA clones by screening of a X. laevis st.24
      embryonic cDNA library. Two partial clones (22 and 63) were obtained and the
      missing 5'-end of the clone 22 was extended by the anchored PCR technique. The
      nucleotide sequence of the resulting clone (22AN) contained an open reading frame
      coding for a protein with 707 deduced amino acids. Three sizes of mRNA (2.9, 5.2
      and 6.6 kb) were detected in blastula (st.9) and early gastrula (st.10) embryos,
      and in hatched tadpole (st.40), but little or no expression was observed in
      morula (st.7) and late gastrula (st.12) embryos, suggesting a physiological
      role(s) of X.laevis BMP-1 in normal embryonic development.

PMID- 8262385
TI  - Cloning and sequencing of the cDNA encoding the murine mammary gland long-form
      prolactin receptor.
AB  - The nucleotide sequence of a 1992-bp cDNA encoding the long form of the murine
      mammary prolactin receptor (PRL-R) has been determined. The deduced 68-kDa
      protein has high sequence identity with long forms of prolactin receptors from
      rat ovary and rabbit mammary gland.

PMID- 8262386
TI  - The human cathepsin D-encoding gene is transcribed from an estrogen-regulated and
      a constitutive start point.
AB  - The 5' flanking sequences, exon 1 and part of intron 1 of the human cathepsin D
      (CTD)-encoding gene (CTD) have been cloned and sequenced. RNase protection
      experiments identified two major transcription start points (tsp) located 14 and
      63 nucleotides upstream of the start codon. The proximal -14, but not the distal 
      63 tsp has upstream near-concensus TATAAA and CCAAT sequences. Estrogens increase
      transcription from the -14 tsp, but not the -63 tsp and CTD is therefore unique
      among estrogen-regulated genes in having estrogen-regulated and constitutive
      transcription. Sequencing approximately 800 bp upstream and 600 bp downstream of
      the tsp failed to identify a consensus 13-bp palindromic estrogen-response
      element (ERE); however, four half-palindrome GGTCA motifs were located within 340
      bp upstream of the -14 bp tsp. Thus, estrogen regulation of CTD may not be
      mediated by a consensus ERE.

PMID- 8262387
TI  - Cloning and expression of a cDNA covering the complete coding region of the P32
      subunit of human pre-mRNA splicing factor SF2.
AB  - We have cloned and expressed a cDNA encoding the 32-kDa subunit (P32) of the
      human pre-mRNA splicing factor, SF2. This cDNA extends beyond the 5'-end of a
      previously reported cDNA [Krainer et al., Cell 66 (1991) 383-394]. Importantly,
      our fragment includes an ATG start codon which was absent from the previously
      reported cDNA, where it was suggested that translation might initiate at a CTG
      codon instead of at an ATG codon. Using the vaccinia virus (Vv) expression
      system, we demonstrate that translation starts at the conventional ATG start
      codon and not at the CTG codon. The protein is synthesized as a pro-protein of
      282 amino acids (aa) that is post-translationally processed by removal of the
      initial 73 aa to a mature protein of 209 aa.

PMID- 8262388
TI  - The human TYRO3 gene and pseudogene are located in chromosome 15q14-q25.
AB  - Partial cDNAs of the human TYRO3 gene, encoding a putative receptor tyrosine
      kinase, and its processed pseudogene (TYRO3P) were cloned from human
      teratocarcinoma cell, bone marrow and melanocyte cDNA libraries. The tyrosine
      kinase homologous domains of TYRO3 and TYRO3P were sequenced and compared with
      each other and with the mouse TYRO3 gene. Abundant levels of the 4.2-kb TYRO3
      mRNA were detected in human brain, and lower levels in other human tissues. TYRO3
      and TYRO3P were both assigned to human chromosome 15q14-q25 by analysis of DNAs
      from somatic cell hybrids.

PMID- 8262389
TI  - A receptor induced by lymphocyte activation (ILA): a new member of the human
      nerve-growth-factor/tumor-necrosis-factor receptor family.
AB  - A 1.4-kb full-length cDNA was isolated from a library constructed from activated
      human T-cell leukemia virus type 1-transformed human T-lymphocytes. Sequence
      analysis identified this cDNA as a new member of the human nerve-growth-factor
      receptor/tumor-necrosis-factor receptor family and as the potential human
      homologue of the murine sequence, 4-1BB. The gene encodes three cysteine-rich
      motifs in the extracellular domain which are characteristic of this receptor
      family, a transmembrane region and a short N-terminal cytoplasmic portion which
      contains potential phosphorylation sites.

PMID- 8262390
TI  - Sequence of a chicken cDNA encoding a GRB2 protein.
AB  - The nucleotide (nt) sequence of a chicken cDNA encoding a protein homologous to
      the human GRB2 (growth factor receptor-binding protein) was determined.
      Remarkably high identities were found on the nt (88%) and deduced amino acid
      sequence (96%) levels.

PMID- 8262391
TI  - Identification of rodent specific primers for screening hamster-human cell lines.

PMID- 8262392
TI  - Sequence of the cDNA encoding Ras GTPase-activating protein from rat.
AB  - We cloned and sequenced a 3296-bp cDNA encoding the rat Ras GTPase-activating
      protein (GAP). Comparison of the nucleotide (nt) and deduced amino acid (aa)
      sequences to those of previously described GAP cDNAs revealed greater than 90%
      identity. Homology is highest between rat and mouse GAP both at the nt (96%
      identity) and deduced aa levels (98% identity).

PMID- 8262393
TI  - An efficient expression vector for stable expression in human liver cells.
AB  - The expression of the bacterial neomycin resistance (NmR)-encoding gene was
      examined under control of the promoter region of the gene encoding the human
      polypeptide chain elongation factor 1 alpha (EF-1 alpha). In a human liver cell
      line, HepG2, the plasmid pEF321-neo directed higher expression of the bacterial
      neo gene than the NmR gene expression vectors using other promoters, like the
      SV40 early region or thymidine kinase of Herpes simplex virus and SV40 early
      region promoter linked to human T-cell leukemia virus-1 enhancer sequences.

PMID- 8262394
TI  - [Use of repellents for protection against vectors of Lyme borreliosis].
AB  - Preparations with repellent effects in the form of lotion and ointment are
      formulated. The active substance is Deet (N,N-diethyl-toluamide) and the base
      constitutes of isopropanil and polyethylene glycol 300 and 1500. The physico
      chemical examinations (Deet identification, examination of density, refraction
      index and Deet contents) have been previously performed. By these investigations
      the Deet structure was conformed, relative density was determined (1,0014) and
      also the refraction index (1,5211) (BP 80; USA XXI). The nitrogen (N) content in
      the resulting substance was 6.44%, in lotion 2.27% and in ointment 0.49%, which
      correspond to the contents of Deet in the formulated preparations. The evolution
      of biological efficacy was performed on Ixodes ricinus ticks. The preparation has
      shown protective effects to the presence of ticks over 60 min under field
      conditions and up to 146 min under laboratory conditions.

PMID- 8262395
TI  - [Epidemiology of Lyme borreliosis].
AB  - Our prospective study covered 1093 patients with epidemiological features and
      demonstrable clinical manifestations of Lyme borreliosis from 1987 to 1992. Basic
      criteria for the inclusion of our patients in the study were: tick bite, erythema
      migrans and antibodies to B. burgdorferi in each patient's serum. Various
      clinical manifestations were found un 1034 (94.6%) patients out of whom 829
      (80.2%) had a history of tick bite, 901 (87.1%) had erythema migrans and 217
      (21.0%) had serologic confirmation of the diagnosis. Inapparent infection was
      discovered in 59 (5.4%) patients. Other Types of skin changes (II and III stage)
      were found in 123 (11.9%) patients. The disease resulted in neurologic, joint and
      cardiac manifestations in somewhat lower percentage of patients (6.3%, 6.6% and
      1.5%, respectively). In the three-year period (1990-1992) microscopic examination
      of the ticks (Ixodes ricinus) collected at several green areas of Belgrade
      confirmed the presence of B. burgdorferi in 29.1 per cent.

PMID- 8262396
TI  - [Investigational methods in Lyme disease].
AB  - After the first clinical case of Lyme disease had been recorded in Belgrade in
      1987 a multi-level research of the disease was undertaken in our country. The
      research was organized on the team basis and was systematized. Ever since the
      beginning epidemiological method has been applied. Professional approach was
      provided by guidelines, while methods and research stages have been provided and
      further developed during seminars and symposiums dealing with lyme disease.
      Research team was comprised of experts from Institute of Public Health of
      Belgrade, Institute for Preventive Medicine of the Medical Military Academy and
      clinicians--specialists in the relevant areas. The team gathered its own precious
      experience in Lyme borreliosis, the disease with precisely defined features and
      well-described manifestations and characteristics. This work describes
      methodology applied in the research of Lyme disease in our country.

PMID- 8262397
TI  - [Etiology and pathogenesis of Lyme borreliosis].
AB  - Some characteristics of B. burgdorferi which have crucial role in the
      pathogenesis of Lyme-borreliosis are described. The pathogenesis of Lyme
      borreliosis is a complex process resulting from inflammation, release of
      interleukin-1, dissemination and adherence of borrelia to different tissues.
      Dissemination of borrelia is facilitated by the increased permeability of the
      blood vessels and active penetration of borrelia through the endothelial
      membranes. Invasion of different type of tissues emerges as a result of B.
      burgdorferi adherence to several types of cells and structures rather evenly
      distributed in human host. Immune response, normally protective, is not efficient
      in eradicating the organisms and can contribute to the illness by development of
      an autoreactive process. Autoreactivity is based on antigenic cross-reactivity
      between epitopes common to borrelia and human host, especially situated on so
      called "heat shock proteins".

PMID- 8262398
TI  - [Clinical characteristics of patients with Lyme disease treated at the Institute
      for Infective and Tropical Diseases 1988-1992].
AB  - In the Institute for infectious and tropical diseases in Belgrade in the period
      1988-1992, 680 patients with Lyme borreliosis have been examined. In most cases
      illness was recognised in the first stage as Erythema migrans. In seven patients
      second and third stage of Lyme borreliosis was cured in hospital.

PMID- 8262400
TI  - [Cutaneous manifestations of Lyme disease and results of our study].
AB  - An investigation of 395 patients with tick bites or suspected tick bites has been
      conducted. Patients were from 14 months to 86 years old. Erythema migrans was
      found in 83 (21.01%), lympocytoma in 2 (0.5%) and scleroderma lesions in 2 (0.5%)
      patients. There were 12 asymptomatic seropositive patients. The presence of
      Borrelia burgdorferi in two Ixodes ricinus ticks was investigated and
      demonstrated.

PMID- 8262399
TI  - [Skin changes in patients with Lyme borreliosis].
AB  - In introduction some clinical characteristics of Erythema migrans, Borrelia
      lymphocytoma and acrodermatitis chronica atrophica has been described. The
      importance of atypical forms of Erythema migrans and the difficulties in
      differential diagnosis of cutaneous manifestation has been stressed. In a
      prospective, and partly retrospective investigation of 1292 persons with tick
      bites, signs of Lyme borreliosis have been found in 18.96%. Number of such
      persons seen in dermatology wards is rising, and 18.2% of these are children less
      than 15 years of age. Patients seen in dermatology are mostly women
      (56.5%:43.5%). Nearly half of the patients with Erythema migrans did not known
      that they had a tick bite (42.5%). Lyme borreliosis was manifested mainly as
      Erythema migrans, 89% of patients. Borrelia lymphocytoma was encountered in 2%,
      and Acrodermatitis chronica atrophicans in 0.4% of patients, significantly less
      than in other reports. Sclerotic skin lesions were found in 4.1% of patients, and
      some macular and urticarial lesions were recorded. An incubation period generally
      less than three weeks preceded to skin manifestations, but in some patients this
      period could not be recorded. Skin lesions were located on lower extremities in
      50.4% of patients, trunk in 25.5%, and upper extremities in 10.5% of patients. In
      87% of patients skin lesions lasted less than three weeks. Symptoms were present
      in 62% of patients. Seropositivity to Borrelia burgdorferi has been found in
      10.2% of patients, mostly three weeks after the tick bite.

PMID- 8262401
TI  - [Lyme disease in children and adolescents].
AB  - 148 children and adolescents with Lyme borreliosis and tick bite or suspection on
      tick bite were examined. The examined patients were aged from 14 months to 24
      years and divided into four age groups. Skin lesions were discovered in 25
      percent of patients with tick bite. Erythema migrans occurred in 91 percent,
      Lymphocytoma in 3 percent and sclerodermatous lesions (Lichen sclerosus et
      atrophicus and Morphea) in 6 percent of patients with Lyme disease. Serologic
      tests on the presence of antibodies to Borreliae burgdorferi were performed in 96
      percent of cases with tick bite. Antibody titer 1:80 or higher in 8 percent of
      patients with tick bite, was discovered. We found positive serologic test results
      in 5 (29 percent) of 29 persons with Erythema migrans, in 4 (4 percent) of 110
      patients with tick bite (without skin lesions), as well as, in 1 patient with
      Lymphocytoma. Antibiotic therapy was applied in all cases with Erythema migrans,
      in person with Lymphocytoma, as well as, in patients with asymptomatic infections
      (patients without skin lesion recalling a tick bite and with antibodies against
      Borrelia burgdorferi). A general sensitivity, to infection with Borrelia
      burgdorferi, is stressed, a fact based on appearance by Lyme borreliosis in all
      age groups even in the newborn children.

PMID- 8262402
TI  - [Lyme disease and pregnancy].
AB  - The authors have investigated Borrelia infection in pregnant women with two or
      more spontaneous abortions, but with no clinical manifestations of Lyme disease.
      In 42 such cases the results were negative. On the other hand, in two cases with
      positive epidemiologic data, but without clinical manifestations of Lyme disease,
      serologic findings were positive. No complications during pregnancy or after
      childbirth were recorded.

PMID- 8262403
TI  - [Erythema migrans after a tick bite in a pregnant woman].

PMID- 8262404
TI  - [Lyme disease in dermatology practice].
AB  - The authors studied a group of 77 patients with Erythema migrans. They were
      treated at the City Institute for Skin and Venereal Disease in Belgrade, over a
      five-year period (1988-1992). A tick bite at the site where Erythema migrans
      later appeared was recalled by 44 (57.1%) of the patients. The interval between
      tick bite and Erythema migrans varied from 1 to 45 days. The indirect IF test was
      seropositive in 11.6% of the Erythema migrans patients. In the present study the
      authors emphasize the importance of early treatment in order to minimize the
      longterm morbidity.

PMID- 8262405
TI  - [Analysis of skin changes in outpatients bitten by a tick during a 1-year
      period].
AB  - Ninety-two patients with tick bites (Ixodes ricinus) visited Outpatient clinic
      for dermatovenerology of Military Medical Academy during a period od one year.
      Tick bites were generally localized on lower extremities and were seasonal in
      character. Most patients were 50-59 years old. Typical early skin manifestations
      in the form of Erythema migrans were diagnosed in 19.56%, and atypical forms of
      erythema in 8.69%. Late manifestations of illness were found on only two
      patients.

PMID- 8262406
TI  - [Epidemiologic characteristics and serologic findings in erythema migrans].
AB  - Our three-year research covered 417 patients with erythema migrans, of both sexes
      and all age groups. Among them 87.3% had a history of tick bite. Average
      attachment of tick to a patients skin was two days. Diameter of erythematous
      lesions was 1-50 cm (with an average of 15.1 cm). Magnitude of the lesion does
      not correlate with the further development of the Lyme disease. IFA test detected
      antibodies against Borreliae burgdorferi in 27.0% of our patients.

PMID- 8262407
TI  - [Rheumatic manifestations in Lyme borreliosis: personal experience in patients
      with oligoarthritis of "unknown" origin].
AB  - Lyme borreliosis is an infectious illness caused by the spirochete Borrelia
      burgdorferi and is transmitted by tick vectors. A prospective study was performed
      from January 1990, to investigate whether Lyme arthritis might have been
      undetected among patients with (unclassified arthritis) oligoarthritis of
      "unknown" aetiology. 210 patients were tested for antibodies to Borrelia
      burgdorferi: 82 patients with oligoarthritis of "unknown" aetiology; 52 patients
      with Reiter's syndrome; 20 patients with seronegative, B-27 positive
      oligoarthritis and 56 controls. Serological testing for Borrelia burgdorferi was
      performed by indirect immunofluorescence assay. The occurrence of positive
      antibodies (1:80) in 11 (13.4%) patients with arthritis of "unknown" aetiology
      was significantly different from the combined control group (1.6%) (p < 0.05).
      Four out of 11 patients remembered a tick bite, two out of 11 patients developed
      erythema migrans after 3 to 10 days. Six weeks later 2 patients developed
      oligoarthritis and one patient after a month. In the remaining 8 patients
      arthritis was the first sign of the disease. Knees were most commonly affected
      (90%). Radiographic abnormalities (osteoporosis, soft tissue swelling) were noted
      in 3 patients. The synovial fluid findings were typical for inflammatory
      arthritides in 6 patients. The diagnosis of Lyme borreliosis was made according
      to following data: origin from an area endemic for Lyme borreliosis, tick bite,
      erythema migrans, significant levels of the antibodies to the Borrelia
      burgdorferi and oligoarthritis. It can be concluded that arthritis may be the
      main manifestation of Borrelia burgdorferi infection.

PMID- 8262408
TI  - [The clinical picture of Lyme disease in neurology].
AB  - Neuroborreliosis of central and peripheral nervous system was found in 24
      patients with typical and atypical clinical syndromes. Information about tick
      bite was obtained in only 1/3 of our patients. Specific antibodies were found in
      3/4 by flourescent antibody test, oligoclonal bands in 1/2, and signs of
      inflammation in cerebrospinal fluid in 1/3 of patients. The majority had
      favourable reaction to antibiotic therapy. It is necessary to investigate every
      case of suspected neuroborreliosis because it can imitate many neurological
      diseases. One must insist on information about the tick bite and/or erythema
      migrans and search for specific antibody production, both in blood and
      cerebrospinal fluid.

PMID- 8262409
TI  - [Clinical picture of cardioborreliosis: from AV block to perimyocarditis].
AB  - The third degree A-V heart block with severe Adams-Stokes attacks in nine
      patients with Lyme borreliosis was described. All patients had similar clinical
      picture: previously healthy with syncope as abrupt onset of the disease. Data on
      skin changes--erythema migrans--were obtained subsequently although the patients
      did not recall being bitten by a tick. Diagnosis was based on clinical
      manifestation, and on positive serologic tests to Borrelia. After the
      administered therapy (on admission atropine 0.5 mg i.v., and/or isoproterenol
      0.02 mcg/kg/min, temporary pace-maker in two patients; and after proved diagnosis
      penicillin 20 mil. unit per day 10 days, and tetracyclin 2.0 gr per day 20 days A
      V block returned to sinus rhythm with normal A-V conduction, and all biochemical
      parameters returned to normal limits. Perimyocarditis is not rare during Lyme
      borreliosis, but in this case infection syndrome is dominant.

PMID- 8262410
TI  - [The most frequent neurologic manifestations of Lyme disease].
AB  - The group of ten patients with Lyme disease, with neurological manifestation, was
      presented. Most of them were treated as patients with different neurological
      diseases until Lyme disease was confirmed. The evidence of Borrelia burgdorferi
      infection, specific blood immunoreactivity and cerebrospinal fluid were
      considered. Most of the patients were with meningoencephalitis. Neuroborreliosis
      clinical manifestations were heterogenous and atypical, making it difficult to
      diagnose.

PMID- 8262411
TI  - [Chronic encephalomyelitis caused by Borrelia burgdorferi. Case report].
AB  - We present a female patient with typical third stage neuroborreliosis with
      progressive chronic encephalomyelitis. One month after a tick bite, in the first
      stage of Lyme disease, she had myalgias during ten days and after one year
      polyarthralgias and polyarthritis. Neurological problems occurred 15 years after
      the tick bite with headache, nystagmus, intentional tremor and spastic
      paraparesis with sphincter disturbances. Etiological diagnosis was established
      after three years. Cytobiochemical findings in cerebrospinal liquor were normal
      but oligoclonal IgG bands were found. Fluorescent antibody test was positive in
      serum (1:75) as well as ELISA (1:447). The patient reacted favourably to
      intravenous crystal penicillin 20 x 10(6) units daily during 18 days. Till now,
      she is in remission and has only mild paresis of the left leg.

PMID- 8262412
TI  - [Clinical manifestations of Lyme disease in pediatric neurology].
AB  - The most important characteristics of Lyme disease in childhood age are
      presented. Difficulties in diagnostics and the most important possibilities in
      differential diagnosis are stressed. It is believed that some cases of lyme
      disease remain unrecognized as the result of poor knowledge about the disease--a
      not unexpected fact considering that lyme disease is described only in the newest
      editions of pediatric neurology.

PMID- 8262413
TI  - [Lyme borreliosis in Belgrade].
AB  - In the period 1990-1992 in Belgrade area a diagnosis of Lyme disease was
      registered in 487 patients. There were 195 men and 292 women. The disease was
      registered in all ages groups, median age 38 y. The tick bite has been confirmed
      in 379 (77.8%) patients. Erythema migrans was the first sign of illness in 387
      (84.6%) patients. The disease resoted in neurologic symptoms in 1.8%, joint
      manifestation in 4.8% and cardiac involvement in 0.9%. Antibodies to Borrelia
      burgdorferi have been detected by indirect immunofluorescence microscopy in
      23.4%. Lyme disease has been registered in all districts of Belgrade.
      Acarological investigations have detected an infection by Borrelia burgdorferi in
      29.0% of investigated ticks.

PMID- 8262414
TI  - [Rhombencephalitis as a manifestation of neuroborreliosis].
AB  - Rhombencephalitis is a rare neurological manifestation of stage II of Lyme
      disease. We presented two cases with no recollection of tick bite nor erythema
      migrans and with cranial nerve nuclei, pyramidal tract and cerebellar tracts
      involvement of sudden onset, inflammatory syndrome in cerebrospinal liquor,
      positive oligoclonal bands and elevated IgG index. A spontaneous remission
      occurred in both cases, but antibiotic was given intravenously for prevention of
      relapses and disease progression.

PMID- 8262415
TI  - [Lyme carditis--case report].
AB  - A patient with Lyme-disease manifested by circulatory disorders of complete AV
      block and ventricle disorder of rhythm was presented. Besides cardiologic
      symptoms during the period of illness, transitory skin and neurologic symptoms
      appeared. The patient has not been treated by antibiotic therapy and after a year
      no late symptoms of illness appeared.

PMID- 8262416
TI  - [The role of echocardiography in the evaluation of cardiac damage in Lyme
      disease].
AB  - Lyme disease is an infectious, multisystem disease involving the skin, heart,
      joints, and nervous system. With its ability to assess cardiac anatomy, chamber
      sizes and myocardial and valvular function, echocardiography is a powerful
      noninvasive tool to investigate possible cardiac involvement in this disorder. We
      studied by echocardiography 15 patients, (6 women and 9 men, mean age 28.5 years,
      range 17 to 42) with clinical and electrocardiographic changes compatible with
      acute myocarditis or myopericarditis. 14 patients (pts) had transitory complete
      heart block and one patient had ventricular extrasystolic arhythmia. A first
      patient group (n = 6) who had a tick bite (Lyme antibody titers were found in
      three patents) was compared with a group (n = 9) without such confirmation. In
      first group two pts had small pericardial effusion and two pts had a nonspecific,
      discrete and small myocardial fibrosis after 3-6 months echocardiographic follow
      up. Chambers sizes and indexes of left ventricular systolic and diastolic
      function were normal. Similar findings were found in the other group. We
      concluded that echocardiographic findings is not specific for Lyme disease, but
      echocardiography is an excellent tool for assessing the presence and degree of
      cardiac dysfunction and therefore provides essential information for the
      management of these patients.

PMID- 8262417
TI  - [Modern immunologic tests in the diagnosis of Lyme borreliosis].
AB  - In this work we described the results that were obtained using various
      immunodiagnostic assays for the detection of lyme borreliosis. Sera of the
      patients that were in acute or chronical phase of the disease were analysed in
      indirect immunofluorescent, immunoenzyme and immunoblot assays which were
      prepared and carried out in our laboratory. As a control for the validity of
      these investigations, we used sera of the healthy people, as well as of the
      patients suffering of lues or rheumatoid illnesses. Results that we obtained
      pointed out the factors responsible for the nonspecific reactions in indirect
      immunofluorescent and immunoenzyme test. The advantage of the immunoblot analysis
      in detecting lyme borreliosis is described in this work.

PMID- 8262418
TI  - [Modern therapy of Lyme disease].
AB  - The treatment of Lyme disease is placed in the centre of more than one medical
      discipline. So far the efficacy of antibiotic therapy application showed various
      results. The results of the treatment of two groups of the patients with Lyme
      disease were presented in the paper. The first group of twenty two patients was
      treated three weeks by the regime I, and the second group of nine patients was
      treated eight weeks by the regime II. During 3-year follow up 50% of the patients
      from the first group and 22% of the patients from the second group had
      recurrences. The total number of the recurrences in the second group was eight
      times less than the total number of the recurrences in the first one. The
      application of antibiotic therapy in the treatment of Lyme disease during eight
      weeks and more can contribute to the falling number of recurrences.

PMID- 8262419
TI  - [Clinico-laboratory diagnosis of Lyme borreliosis--personal experience].
AB  - Between May 1992 and February (second half) 1993 two hundred patients with the
      history of tick bite have been examined at the Institute for Infectious and
      Tropical Diseases "Dr Kosta Todorovic". Of the above 200 persons, 103 of them
      have had clinical/epidemiological evidence of Lyme disease (i.e. Erythema
      migrans). In order to establish the degree of seroconversion in this stage of
      Lyme disease, blood of each patient has been tested by PHA and IFA methods. Blood
      from each patient has been drawn in pairs, immediately before and after the
      treatment. By method of PHA we have analyzed 186 sera and found 23 positive
      results. By method of IFA we have analyzed 10 sera and found one positive result.
      By Comparative testing we have analyzed 10 sera, obtaining 5 positive results by
      PHA and 3 positive results ba IFA.

PMID- 8262420
TI  - [Results of clinico-laboratory and serologic studies in a group of patients with
      tick bites].
AB  - Lyme borreliosis (LB) represents a most pressing problem for the modern medical
      pathology, from a number of different aspects. The paper describes the results of
      clinical laboratory and serological tests in a group of patients (100 tested
      persons) after a tick (Ixodes) bite and analyzes their diagnostic and prognostic
      value.

PMID- 8262421
TI  - [Therapy of Lyme disease].
AB  - Lyme borreliosis is manifested as a multisystemic disease, depending on the
      clinical picture and severity of the illness in acute, subacute and chronic form.
      The disease evolves in three stages. A choice of therapy, route of administration
      and duration of treatment depend on the stage of the disease. The treatment of
      Lyme disease requires the use of antibiotics. The current antimicrobial therapy
      is successfully performed with the following antibiotics from ICN GALENIKA
      assortment. Natural penicillins-PENCILLIN CRYSTALISATUM for i.v. administration;
      JUGOCILLIN for i.m. administration and BIMEPEN which is administered orally; Semi
      synthetic penicillins-SINACILIN, tetracycline AMRACIN; Cephalosporins- the most
      important is LONGACEPH- the third generation cephalosporin). The recommended
      current treatment of Lyme disease requires employment of up-to-date therapeutic
      approach.

PMID- 8262422
TI  - [The importance of Lyme borreliosis in veterinary medicine].
AB  - A study of literature concerning Lyme borreliosis related to animals was done. In
      the research work the epidemiology, pathogenesis, diagnosis and treatment of
      horses, cattle and dogs affected with Lyme borreliosis have been discussed. The
      clinical signs of Lyme borreliosis in horses are: chronic weight loss, sporadic
      lameness, laminitis, low grade fever, swollen joints, muscle tenderness and
      anterior uvetitis. In addition to these clinical sings, neurological sings such
      as depression, behavioral changes, dysphagia and encephalitis can be seen in
      chronic cases. Cattle affected with acute Lyme borreliosis often show fever,
      stiffness, swollen joints and decreased milk production. Chronic weight loss,
      laminitis and abortion are also a possible outcome of borreliosis in cattle. An
      early infection of Lyme borreliosis in dogs may give evidence of inapetenca,
      lethargy, lyphadenopathy, and an acute onset of stiffness or pain while a
      recurrent intermittent nonerosive arthritis is a more advanced manifestation of
      canine Lyme borreliosis. Glomerulonephritis and tubular damage secondary to
      Borrelia burgdorferi infection have been reported to occur in normally infected
      dogs. In an endemic area atrioventricular heart block has also been reported. The
      underlying pathogenesis of Lyme disease is still unknown. The diagnosis of
      clinical Lyme borreliosis is difficult and it depends on a successful recognition
      of clinical signs, a history of possible exposures to the infection and on
      serologic testings. The therapy of Lyme borreliosis in animals is based upon the
      principal therapy of this disease in human medicine.

PMID- 8262423
TI  - [Lyme disease in human medicine].
AB  - Six years of investigations of Lyme disease in our country has offered an
      opportunity for better understanding of this "new" illness, which is both a
      medical and a health problem. The number of patients with Lyme disease is found
      to be similar to the number of patients in other countries. Human infections
      occur in different areas, rural and urban settings. A high level of collected
      ticks with Borrelia burgdorferi, suggests a considerable risk of human infection
      after a tick bite. Difficulties in diagnosing of Lyme disease are connected with
      different clinical symptoms and signs of the illness a poor health service
      personnel knowledge og the disease, and the lack of reliable and more convenient
      laboratory tests for confirmation of the diagnosis. A team work and a
      multidisciplinary aspect in the investigations and the routine work provide a
      solid base for a better understanding and gathering much more experience in this
      field. The individual protection remains a basic control measure, and each person
      can do the most for self protection. An activity in the health education is also
      of a very great importance.

PMID- 8262424
TI  - [Ecology of Borrelia burgdorferi].
AB  - Much still remains to be understood about ecology of Borrelia burgdorferi which
      is transmitted by a number of ticks belonging primarily to the Ixodes complex,
      known to feed on different animal hosts and humans. This article pretends to be a
      review of previous knowledge of Borrelia burgdorferi ecology. Special emphasis is
      placed on the preliminary results of an investigation conducted in Yugoslavia on
      the risk of developing lyme borreliosis after a tick bite (Ixodes ricinus). Lyme
      borreliosis was studied prospectively in 147 persons with tick fastened on them.
      Dark-field microscopic examination of tick mitgut revealed that 11 (7.9%) od 147
      Ixodes ricinus were infected with Borrelia burgdorferi. Lyme borreliosis was
      demonstrated in only one (0.6%) of all persons bitten by ticks infected with
      Borrelia burgdorferi. In conclusion, these preliminary data indicate that in
      Yugoslavia lyme borreliosis infrequently occurred after a tick bite.

PMID- 8262425
TI  - [Vectors of Borrelia burgdorferi].
AB  - During the period 1990-1992-5,915 ticks were collected and identified in the area
      of Belgrade. Identification has shown that 99.8% were Ixodes ricinus and 0.2%
      Dermacentor marginatus. Infection with Borrelia burgdorferi was found in 27.0% to
      31.7%. Females were more often infected than males and nymphs more often than
      larvae. Tick infection was at lowest degree in parks, little bit higher in woods
      and highest in mixed park-wood areas. Out of 28 locations, six can not be defined
      as foci of Lyme borreliosis, two are defined as potential foci and 20 as active
      foci of Lyme borreliosis. In a three year period we have isolated Borrelia
      burgdorferi in five occasions; in one occasion from ticks collected in Barajevo
      and in four occasions from ticks collected in Kosutnjak.

PMID- 8262426
TI  - [A theoretical model for the study of Lyme borreliosis].
AB  - This article is a short review of: a) development of theory on natural foci of
      communicable diseases in man, b) methodological approach to the investigation of
      natural foci, e.g. theoretical model in their investigation, and c) the use of
      theoretical model in the investigation of Lyme borreliosis. A great number of
      multidisciplinary studies on natural foci zooanthroponoses conducted through many
      years, in which ecological approach and numerous methods were applied, commencing
      from studies of the processes at the level of molecules, genes, cells, tissues,
      organismus, populations and species, contributed to the knowledge that
      epizootical process of natural foci of zooanthroponoses is almost an ideal
      natural model. Its investigation allows the establishment of the rules of
      epidemiological process which, for many reasons (ethical above all), is not
      accessible for experimental studies. On these principles a general block model
      has been worked out, which serves for the estimation of epidemiological
      manifestations of natural foci zooanthroponoses, and which, applied to Lyme
      borreliosis, enables the determination of active and potential foci and the
      estimation of the degree of risk of man infection in determined foci. Data
      obtained in such a way allow planning and application of adequate preventive
      measures.

PMID- 8262427
TI  - [Epidemiologic characteristics of Lyme borreliosis in Vojvodina].
AB  - In the period 1988-1992 in the region of Vojvodina diseases caused by Borrelia
      burgdorferi were investigated for the first time. This investigation encompassed
      398 persons with tick bites. There were 340 clinically healthy and 58 affected by
      Lyme borreliosis. Lyme borreliosis was registered in all age groups. The youngest
      patient was 5 and the oldest 75. Erythema migrans, clinical disease marker, was
      found in 94.8% of affected persons. Rheumatic disorders--arthralgiae were found
      in 3.5% and Sclerodermia circumscripta in 1.7%. Antibodies to Borrelia
      burgdorferi antigen were found in 46.9% of 32 patients tested by IFA test. In 55
      (94.8%) patients the infestion took place in region of Vojvodina.

PMID- 8262428
TI  - [Borrelia burgdorferi seropositivity in the region of Cacak].
AB  - Seropositivity to Borrelia burgdorferi found in the population of Cacak area,
      suggests that the illness in different forms is present in this population.
      Failure in detection of early symptoms contributes to development of the second
      and the third stage of illness, in which the treatment is connected with more
      difficulties. A high natural focus activity has been confirmed by seropositivity
      found in sera of 11% of patients tested.

PMID- 8262429
TI  - [Exposure to Ixodes ricinus bites among soldiers].
AB  - Results of an investigation on the exposure to tick bites among soldiers in 6
      permanent army structures on the territory of Belgrade are shown. Four army
      structures were found to be active foci of Lyme borreliosis. Infection rates
      among Ixodes ticks were from 10% in urban structures to 42.1% in rural
      structures. Exposure of soldiers to tick bites was the largest in rural army
      structures--3.40%, while in urban army structures it was 0.14%. Among 38 tick
      bitten army members, 1 developed clinical manifestation as Lyme borreliosis
      (2.6%).

PMID- 8262430
TI  - [Distribution of Ixodes ricinus ticks in Yugoslavia].
AB  - In this paper the authors present distribution of tick Ixodes ricinus in both
      republics of Yugoslavia--Serbia and Montenegro. The ticks were collected from
      domestic animals and humans sporadically. The determination showed following
      species: Ixodes ricinus, I. persulcatus, I. hexagonus, Dermacentor marginatus, D.
      pictus, Rhipicephalus bursa, R. sanguineus, Haemaphysalis punctata, H. inermis,
      H. sulcata, H. leporis-palustriis, H. concinna, Boophilus (margaporus)
      calcaratus, Hyalomma savignyi, H. excavatum, H. detritum and H. rufipes. The
      species I. ricinus has been detacted in all parts of the country.

PMID- 8262431
TI  - [Ticks in the region of Belgrade].
AB  - The paper gives a brief introduction concerning the role of ticks in transmission
      of numerous diseases to both animals and humans. Methods of work, research goals
      and finally, results of tick findings on animals and people in Belgrade area are
      presented. Occasional findings of those arthropodes in various urban areas have
      also been described. The collected ticks belong to the species Ixodes ricinus and
      Rhipicephalus sanguineus. The authors conclude that ecologic research of ticks
      should be continued and expanded not only in Belgrade but in other areas of the
      country as well.

PMID- 8262432
TI  - [The first isolation of Borrelia burgdorferi in Apodemus flavicollis in
      Yugoslavia].
AB  - Small rodent species, as well as their ectoparasitic fauna, and the presence of
      Borrelia burgdorferi in their blood and internal organs (liver and spleen) was
      investigated, at two locations (Kosutnjak, Lipovicka suma) in Belgrade. Animals
      were caught between September 15-17, 1992. On location Kosutnjak two Apodemus
      flavicollis were trapped and Borrelia burgdorferi was isolated from the spleen of
      one of them. On location Lipovicka suma 13 rodents were trapped as follows: 10
      Apodemus flavicollis, 2 Apodemus agrarius and one Mus musculus. In these the
      presence of Borrelia burgdorferi was not determined. Ectoparasits Ixodes ricinus,
      Nesopyllus fasciatus and Haemogamasus spp. have been found. The location
      Kosutnjak can be considered as an active focus of lyme borreliosis.

PMID- 8262433
TI  - Gifts of the moment.

PMID- 8262434
TI  - The ethics of treatment decision making: the elderly patient's perspective. The
      vast resources--and costs--of available technology makes it crucial that we
      understand what the patient wants.

PMID- 8262435
TI  - Vision and hearing screening in cognitively impaired older adults.

PMID- 8262436
TI  - Spirituality and the chronically ill Christian elderly.

PMID- 8262437
TI  - Lessons in caring: a 'care by caregiver' program.

PMID- 8262438
TI  - Loneliness and the spouse of the geriatric patient. Seven guidelines may keep a
      spouse's loneliness from becoming overwhelming.
AB  - Loneliness is a painful human experience to which spouses of the geriatric
      patient are particularly vulnerable. The nurse is frequently in a position to
      assess not only the patient but the spouse. When factors that may lead to
      loneliness are present, the nurse can intervene to prevent loneliness. When
      symptoms of loneliness are present in the spouse or patient, the nurse may act to
      alleviate disabling feelings of isolation.

PMID- 8262439
TI  - Predicting loneliness in the hospitalized elderly: what are the risk factors?

PMID- 8262440
TI  - Helping older adults find serenity. Are there potential nursing interventions
      that may help older adults reach a serene state?

PMID- 8262441
TI  - Choices in the long-term care continuum. Nurses need to educate clients and
      family members about the choices in long-term care.

PMID- 8262442
TI  - Nurses estimate elderly malnutrition.

PMID- 8262443
TI  - Drugs in development for Alzheimer's disease.

PMID- 8262445
TI  - Multiresistant strains of Escherichia coli isolated from the rumen of young
      calves.
AB  - Five multiresistant strains of Escherichia coli were isolated from the rumen
      fluid of young calves. Resistance to tetracycline and ampicillin was found to be
      associated with the transfer of a 6.4 kbp plasmid present in two investigated
      strains.

PMID- 8262444
TI  - Production of threonine by Brevibacterium flavum containing threonine
      biosynthesis genes from Escherichia coli.
AB  - Genes of the threonine operon of Escherichia coli were used for the construction
      of a Brevibacterium flavum strain excreting threonine. Using the shuttle vector
      pCEM300 and a newly constructed shuttle vector pEC71 (7.1 kb, Kmr/Nmr), various
      plasmids carrying E. coli thr genes were prepared. Mutants resistant to the
      threonine analog 2-amino-3-hydroxyvaleric acid (AHV) were isolated after the
      ethyl methanesulfonate treatment of B. flavum carrying these recombinant
      plasmids. A mutant of B. flavum CCM 351 carrying the cloned genes thrA and thrB
      accumulated 12 g/L of threonine after 48 h of cultivation.

PMID- 8262446
TI  - Degradation of 2-chlorobenzoic and 2,5-dichlorobenzoic acids in pure culture by
      Pseudomonas stutzeri.
AB  - A strain of Pseudomonas stutzeri KS25 utilizing 2-chlorobenzoic and 2,5
      dichlorobenzoic acids as the sole carbon and energy source was isolated from
      polychlorophenol-contaminated soil and sewage, using the method of enrichment
      cultures. This strain was also able to grow on 2-fluoro-, 2-iodo-, 2-bromo- and
      2,5-dihydroxybenzoate, but did not utilize 3-, 4-chloro-, 2,4- and 2,6
      dichlorobenzoates as the sole carbon and energy source, however, it cometabolized
      3-chloro-, 2,4- and 2,6-dichlorobenzoates, but not 4-chlorobenzoate. The yield of
      released chlorine during utilization of 2-chloro- and 2,5-dichlorobenzoates
      amounted to 100% of the theoretical. The concentration of 2-chloro- and 2,5
      dichlorobenzoates, not substantially inhibiting the isolated microorganism, was
      within the range 0.25-0.5 and 2.5-3.0 g/L, respectively.

PMID- 8262447
TI  - Degradation of 2-chlorobenzoic and 2,5-dichlorobenzoic acids in soil columns by
      Pseudomonas stutzeri.
AB  - The heterocontinuous flow cultivation technique was used for the study of 2
      chlorobenzoic and 2,5-dichlorobenzoic acid degradation in soil columns inoculated
      with Pseudomonas stutzeri. 2-Chlorobenzoic and 2,5-dichlorobenzoic acids
      disappeared from the soil columns within 8 and 12 d, respectively. The presence
      of the haloaromatics increased the survival of strain KS25 in soil. Viable cell
      numbers in the soil columns flushed with 2-chlorobenzoic and 2,5-dichlorobenzoic
      acids were 1.3 and 2 times higher, respectively, than those without the
      chlorobenzoic acids after 30 d of incubation.

PMID- 8262448
TI  - Monensin has no effect on growth and metabolism of Megasphaera elsdenii.
AB  - A rumen strain of Megasphaera elsdenii was grown on glucose and lactate in
      monensin-free and monensin-supplemented medium (10 mg/L). Monensin had no effect
      on growth rate, growth yields, metabolic pattern and composition of cells. Growth
      yields of dry matter and protein were higher in cultures supplied with glucose
      than in cultures supplied with lactate. The bacterium compensated the lower gain
      of energy from fermentation of lactate by rapid utilization of this substrate.
      Cells grown on glucose contained more saccharide and less protein than lactate
      grown cells.

PMID- 8262449
TI  - Relationship between antifungal activity and hydrophobicity of kojic acid
      derivatives.
AB  - Twenty three kojic acid derivatives were tested in the agar diffusion test
      against twenty five dermatophytic fungi. The inhibitory effects at equal doses
      (10 mg/L) were correlated with the 1-octanol-water partition coefficients of the
      compounds. An improvement in antifungal activity can be achieved by increasing
      the hydrophobicity of the compounds.

PMID- 8262450
TI  - Aliphatic 1,2-alkanolamines--inhibitors of beta-glucanase from Candida utilis.
AB  - Aliphatic 1,2-alkanolamines inhibited beta-glucanase from Candida utilis. The
      highest inhibitory effect was observed with 1-dodecylamino-3-chloro-2-propanol
      (Ki = 1.0 mumol/L) and it was much higher than that of D-glucono-delta-lactone.
      Simple 1,2-alkanolamines, like 2-aminoethanol or 2-methylaminoethanol, did not
      exhibit any significant inhibitory effect.

PMID- 8262451
TI  - The fluorescence brightener Rylux BSU induces dimorphism in Basidiobolus ranarum.
AB  - The fluorescence brightener Rylux BSU (RBSU) showed an affinity for
      polysaccharide components of cell walls and accumulated in the extension zones of
      hyphal apices in Basidiobolus ranarum. It inhibited the polarized growth of
      mycelial hyphae and induced isotropic growth resulting in spherical thick-walled
      cells up to 456 microm in diameter. On the inner cell wall surface, massive
      protuberances were formed. The cell wall and protuberances were positive in PAS
      and the Grocott method and stained with fluorochromes Blankophor BA, Calcofluor,
      Uvitex 2B, Rylux BSU and FITC-labeled WGA- and ConA-lectins. The WGA-FITC
      fluorescence intensity of the wall's outermost layer, if not connected with
      neighbouring cells, and the fluorescence intensity of the innermost layer and of
      some protuberances mainly in their apical parts were on the average twice higher
      than the fluorescence intensity of the remaining wall material. RBSU binding to
      the cell wall material was stable. The process of converting from polarized to
      isotropic growth was reversible, depending upon contact with RBSU-containing
      medium. Repeated transfers of cells from RBSU-containing medium to an RBSU-free
      medium resulted in the development of apical swollen dumbbell-shaped cells.

PMID- 8262452
TI  - Application of the cell growth and DNA-inhibition tests for characterizing
      sulfate pulp mill waste waters.
AB  - The evaluation of cytotoxic and genotoxic effects of selected technological
      samples from sulfate pulp mill waste waters by using the growing activity method
      for pseudodiploid fibroblasts V79 from lungs of the Chinese hamster and from
      human heteroploid fibroblasts EUE has been described along with the DNA
      inhibition test for studying the synthesis of DNA after it has been influenced by
      the above-mentioned samples. Both the waste solution produced during the
      preparation of bleaching agents and the liquor generated after using hypochlorite
      (1st stage) as a fourth filter (after the production of paper pulp) are cytotoxic
      waste waters. Black liquor generated during the production of viscose pulp may
      have mutagenic effects and black liquor obtained from the production of paper
      pulp is characterized by mutagenic as well as carcinogenic effects.

PMID- 8262453
TI  - Testing of mutagens and cigarette side smoke using a modified Salmonella assay.
AB  - The results of two mutagens are presented in order to demonstrate the sensitivity
      of a modified Salmonella microsuspension assay (Kado et al. 1983) compared to the
      standard plate-incorporation assay. The first procedure was 2.4-7.3 times more
      sensitive in detecting the mutagens, 2-aminoanthracene and sodium 5-(3-nitro-2
      furyl)acrylate. Methanol extract and cyclohexane extract from cigarette side
      smoke enhanced the response in the absence and presence of S9 activation mixture
      with the TA 98 strain. The cigarette side smoke mutagens were detected in 10
      times lower volume samples (0.1 m3 of sampled air) in the microsuspension assay
      than in the plate incorporation assay.

PMID- 8262454
TI  - Survey of susceptibility to selected antibiotics of Pseudomonas aeruginosa
      strains isolated from patients with tumor disease and their relationship to
      serotype.
AB  - A total of 51 Pseudomonas aeruginosa strains had been isolated over a year from
      patients with tumor diseases in the National Institute of Oncology in Bratislava.
      All strains were subjected to serotyping; in 45 strains quantitative
      susceptibility to selected antibiotics was determined by the microdilution
      method. When comparing susceptibility of individual serotypes, resistance of
      strains belonging to serotype O12 to a number of beta-lactam, aminoglycoside and
      quinolone antibiotics was found. In addition, resistant strains occurred even
      among serotype O4 and polyagglutinating strains. The resistant strains as
      causative agents of nosocomial infections may represent a serious risk
      particularly for patients of oncological wards.

PMID- 8262456
TI  - My experience as a courier.

PMID- 8262457
TI  - Neural control of insulin secretion.

PMID- 8262455
TI  - Peripheral membrane molecules of leukocytes and NK cytotoxicity.
AB  - Some leukocyte effector cell-surface molecules movement toward the adjoining
      target cells takes place during the reaction of NK cytotoxicity (NK R). The
      majority of the moving molecules are usually anchored via a divalent-ion
      dependent interaction (PMM-M2+). The released PMM-M2+ can interact also with the
      secreted tumor necrosis factor alfa (TNF-alpha). In agreement with PMM-M2+
      movement, the number of TNF-alpha binding sites on the target cell surface
      increases during NK R. In addition, antibodies against PMM-M2+, as well as D
      mannose- or N-acetyl-D-glucosamine-terminated oligosaccharides of PMM-M2+ inhibit
      NK R. A more detailed analysis of PMM-M2+ with monoclonal antibodies used flow
      cytometry and cell-surface biotinylation. Only 3 of 31 tested CD antigens (CD2,
      LAK-1 and CD45) were passed through this first strongly restricted experimental
      screening. The EDTA-released LAK-1 antigen, but not CD2 and CD45, interact with
      TNF-alpha and cell surface via a mannose-inhibitable interaction dependent on the
      presence of Ca2+ ions. The mechanism of possible participation of PMM-M2+ in
      cytotoxic events is discussed in relation to Ca2+ influx and subsequent cytolysin
      secretion.

PMID- 8262458
TI  - Specific and functional insulin receptors in rat renal papilla.
AB  - To investigate a possible action of insulin on the rat kidney papilla, the
      binding of 125I-insulin to papilla microsomes was examined. This binding was
      specific to insulin in that it was displaced by increasing concentrations of
      unlabelled porcine insulin and to a lesser extent by porcine proinsulin and IGF
      I, but not by IGF-II and bGH. Scatchard plot of the binding data was curvilinear
      consistent with either two classes of receptors with different affinities or a
      single class of receptors that showed negative cooperativity. A small fraction of
      125I-insulin (maximum 2%) was degraded during incubation, but with a Km two order
      of magnitude higher than the constant of affinity for binding. Insulin stimulates
      the incorporation of phosphate to phosphatidylcholine in a dose-dependent manner,
      reaching a maximum with 10 nM insulin. This data showed both the presence of
      specific insulin receptors in the kidney papilla and an insulin action through
      the synthesis of phospholipids by insulin.

PMID- 8262459
TI  - Preliminary investigations of bony fish--tench (Tinca tinca L.)--erythrocyte
      insulin receptors.
AB  - Specific insulin receptors were identified on tench (Tinca tinca L.)
      erythrocytes. The samples of blood from 3-4 fish per experiment were pooled in
      summer. Erythrocytes were washed twice with saline solution, then centrifuged and
      resuspended in the assay buffer. Incubations were carried out in 0.5 ml samples
      containing 10(9) cells, with addition of 0.03 nmol/l of 125I-pork insulin in the
      absence or presence of unlabelled pork or salmon insulin (0.05-2000 nmol/l) for
      24 h at 4 degrees C. Calculated from seven experiments specific binding of 125I
      insulin was 6.2 +/- 0.2% (mean +/- SD). Scatchard analysis of the binding data
      from insulin radioreceptor assay showed two different binding sites with high
      (HAIR) and low (LAIR) affinity. KD values were 0.82 +/- 0.17 nmol/l and 2.05 +/-
      1.62 mumol/l, and maximal binding capacity (Bmax) 24.9 +/- 1.6 fmol/10(9) cells
      and 17.5 +/- 12.2 pmol/10(9) cells, respectively (N = 4). If compared with pork
      insulin, six to seven times more of salmon insulin was required to displace 50%
      of iodine labelled hormone. Thus, insulin receptors of tench erythrocytes are
      similar to those described in other species of fish and other lower vertebrates.

PMID- 8262460
TI  - Development of glucose intolerance in obese (fa/fa) Zucker rats.
AB  - Development of glucose intolerance in genetically obese (fa/fa) rats was
      investigated. Comparisons were made with lean (FA/?) control rats. Oral glucose
      tolerance tests were performed in 7-8 weeks, 9-10 weeks, 12-13 weeks and 16-17
      weeks old rats. Irrespectively of age, the obese rats showed impaired glucose
      tolerance and insulin sensitivity compared with age-matched lean rats. While in
      FA/? rats only minor changes of glucose-stimulated insulin secretion and glucose
      tolerance were observed with progression of age, glucose intolerance in obese
      animals became more pronounced with aging. Obese rats older than 12-13 weeks
      showed no further progression of glucose intolerance. Glucose-stimulated insulin
      secretion increased with aging, but basal insulinemia was unaffected. Hence, we
      conclude that glucose intolerance and insulin resistance in genetically obese
      (fa/fa) rats is almost completely developed with approximately 12 weeks.

PMID- 8262461
TI  - Long-term exposure to SMS 201-995 inhibits proliferation and calcitonin release
      in neoplastic C-cells.
AB  - The effect of the long-acting somatostatin analogue SMS 201-995 on cellular
      proliferation and calcitonin production was examined in rMTC 6-23 cells. A dose
      dependent inhibition of calcitonin release and cellular calcitonin content was
      obtained in cells exposed to SMS 201-995 for 72 hrs. The dose-dependent
      antiproliferative effect of SMS 201-995 (10(-8)-10(-6) M) was significant after
      72 hrs of exposure. SMS 201-995 has an inhibitory effect on calcitonin secretion
      and synthesis as well as on the growth of C-cells.

PMID- 8262462
TI  - Microalbuminuria in a normotensive insulin-treated diabetic population.
AB  - Thirty-five insulin-treated diabetics without overt proteinuria or hypertension,
      and taking no antihypertensive medications were screened at three clinical
      centers for the presence of microalbuminuria. In addition to the presence of
      albuminuria, patients were evaluated for duration and type of diabetes,
      retinopathy, blood pressure, and degree of diabetic control. In these patients,
      it was possible to examine the degree of microalbuminuria as a function of
      systolic and diastolic blood pressures, age and sex of the patient, site of
      recruitment, duration of diabetes, and glycemic control. On multivariate
      statistical analysis, systolic blood pressure was the only factor that
      contributed to microalbuminuria. An additional 37 patients had urinary albumin
      excretion measured, although biochemical and clinical characteristics were
      incompletely determined. Blood pressures were documented to be normal in 23 of
      these individuals, while the other fourteen were normal by history. The range of
      urinary albumin excretion was comparable in the patients with complete data bases
      and those without. Overall, 22.2% of the normotensive insulin-treated patients
      screened had microalbuminuria, 5.5% had gross albuminuria, while 72.2% had normal
      urinary albumin excretion. We agree with previous reports that microalbuminuria
      is relatively uncommon in the normotensive diabetic population, but further
      conclude that even in the context of "normal" blood pressure, systolic blood
      pressure should be carefully observed in diabetic patients. It is possible that
      these individuals should be considered for more aggressive monitoring programs,
      e.g., ambulatory blood pressure recording.

PMID- 8262463
TI  - Effect of captopril, an inhibitor of the converting enzyme on naloxone induced
      secretion of ACTH and LH in man.
AB  - It has been previously shown that endogenous opioid peptides suppress human ACTH
      and gonadotropins secretion via hypothalamic mechanism. Since the angiotensin
      converting enzyme can participate in the metabolism of opioid peptides, this
      study examined the action of Captopril, an angiotensin converting enzyme
      inhibitor, on corticotropin and gonadotropin (LH and FSH) release induced by the
      opiate antagonist naloxone in man. Seven male hypertensive volunteers (aged 30
      52) were treated with A) saline; B) naloxone 8 mg iv as a bolus followed by an iv
      infusion of 4 mg/h; C) naloxone as above after pretreatment with captopril 150
      mg/day for 15 days; D) captopril alone. Naloxone significantly stimulated ACTH
      and LH secretion when compared with the saline infusion. This stimulating effect
      was taken as an indirect evidence for a tonic opioid inhibition on pituitary
      hormones release. The pre-medication with captopril significantly enhanced the
      ACTH and LH response to the opiate antagonist naloxone, but captopril alone did
      not modify ACTH and LH values when compared to saline. The results would suggest
      that captopril interferes with the opioid regulation of human ACTH and LH
      secretion probably by blocking the proteolytic degradation of opioid peptides.

PMID- 8262464
TI  - Effect of zinc treatment on serum thyroid hormones in uremic patients under
      peritoneal dialysis.
AB  - In order to evaluate the effect of zinc (Zn) deficiency on thyroid abnormalities
      in chronic renal failure, a Zn supplement (100 mg/day, p.o.) was given for four
      weeks to eight uremic patients under peritoneal dialysis. Zn supplementation
      increased plasma levels of TSH (5.8 +/- 0.7 to 7.4 +/- 0.7 mU/l, p < 0.02), T4
      (61.6 +/- 3.9 to 93.9 +/- 6.2 nmol/l, p < 0.01), T3 (1.31 +/- 0.14 to 1.70 +/-
      0.18 nmol/l, p < 0.01) and Zn (7.23 +/- 0.45 to 12.27 +/- 0.76 mumol/l, p <
      0.01). A close correlation was found between changes in plasma levels of Zn and
      changes in TSH (r = 0.82), T4 (r = 0.55) and T3 (r = 0.64), suggesting that Zn
      deficiency may play a role in the biosynthesis or release of hormones of the
      hypothalamic-pituitary-thyroid axis in chronic renal failure.

PMID- 8262465
TI  - Distribution of oxytocinergic glucocorticoid target neurons in the rat
      hypothalamus.

PMID- 8262466
TI  - Plasma glucose and capsaicin-sensitive nerves in the fed rat during exercise.

PMID- 8262467
TI  - The effect of smoking on serum placental alkaline phosphatase levels in
      pregnancy.

PMID- 8262468
TI  - Growth hormone administration and carbohydrate metabolism.

PMID- 8262469
TI  - Effects of growth hormone on the metabolism of lipids and water and their
      potential in causing adverse events during growth hormone treatment.
AB  - GH effects certain changes in the metabolism of lipids and body water in humans.
      The effects of GH, such as high blood pressure, an increase in cholesterol and
      triglycerides, and lipoatrophy, among others, must, however, be seen in the
      context of the diverse disorders being treated. The risks faced in acromegaly,
      for instance, are not necessarily shared by Turner's syndrome patients treated
      with GH. The various metabolic effects of GH could thus be said to lead to
      adverse events in certain risk groups, which makes the monitoring of relevant
      parameters essential during treatment with GH.

PMID- 8262470
TI  - Immunological findings in growth hormone-treated patients.
AB  - In vivo studies in experimental animals and in vitro studies using human
      lymphocytes have indicated that growth hormone (GH) is important for the
      development and function of the immune system. This is most clearly illustrated
      by the underdevelopment of the thymus in dwarf Snell mice, which is prevented by
      GH treatment. In contrast, in vivo studies in humans have generally shown only
      minor alterations of immune function in GH deficiency. GH administration to
      children with various growth disorders may lead to variable and subtle changes in
      some laboratory parameters of immune function, but no clinical symptoms
      associated with immune dysfunction have been reported.

PMID- 8262471
TI  - Comparison of complete and incomplete suppression of pituitary-gonadal activity
      in girls with central precocious puberty: influence on growth and predicted final
      height. The German-Dutch Precocious Puberty Study Group.
AB  - The question as to whether treatment with short-acting or with slow-release
      gonadotropin-releasing hormone (GnRH) agonists has different effects on growth
      and bone maturation when treating girls with central precocious puberty has not
      yet been studied. In a meta-analysis, we compared 21 naive girls with central
      precocious puberty who were treated with buserelin with 22 naive girls with
      central precocious puberty who received Decapeptyl in depot form. Treatment
      lasted for at least 18 months. At the start of therapy, chronological age, bone
      age, growth velocity and pubertal stage in the two groups were very similar.
      During the first 6 months of treatment, significantly more phases of incomplete
      suppression of pituitary-gonadal activity occurred in the buserelin group. As a
      result, growth velocity and bone maturation (delta bone age/delta chronological
      age) remained significantly higher than in the Decapeptyl Depot group (p < 0.0001
      and p < 0.01, respectively). In contrast to the Decapeptyl Depot group, the
      height standard deviation score (SDS) for bone age in the buserelin group did not
      change significantly in the first 6 months of treatment, and the predicted adult
      height decreased. Between the 6th and 18th months of therapy, the development of
      growth rate, delta bone age/delta chronological age, height SDS for bone age and
      predicted adult height in both groups became almost identical. However, the rate
      of growth and bone maturation in the buserelin group remained faster than in the
      Decapeptyl group, though not significantly so. The mean predicted adult height
      had risen significantly after 18 months in the Decapeptyl Depot group but not in
      the group treated with buserelin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262472
TI  - Growth in children after bone marrow transplantation.
AB  - Growth velocity pattern and growth hormone (GH) secretion were evaluated in 18
      prepubertal patients (13 males, 5 females), receiving an allogeneic (7 patients)
      or autologous (11 patients) bone marrow transplantation (BMT). Children were
      affected by oncological or hematological malignancies and the age range was
      between 2 and 11 years. Nine patients received a conditioning regimen consisting
      of chemotherapy and fractionated total body irradiation (TBI) (12 Gy in 6
      fractions over 3 days), whereas 9 children also received previous prophylactic
      cranial irradiation during first-line chemotherapy. GH secretion in response to
      pharmacological stimuli (insulin, arginine and/or L-Dopa) was evaluated when
      growth failure occurred. The 9 prepubertal patients who had received previous
      prophylactic cranial irradiation during first-line chemotherapy, showed a
      significant decrease in growth rate already 1 year after BMT and this reduced
      growth rate presented a progressive further decrease in the 2nd and 3rd year
      after BMT. On the contrary, in the 9 prepubertal children treated with TBI and
      chemotherapy alone, growth rate presented an impressive decrease only during the
      3rd year. In the two groups of patients, pretransplantation growth rates were
      comparable, while, due to the earlier growth failure in children receiving TBI
      and previous prophylactic cranial irradiation, mean standard deviation score
      (SDS) significantly differed at 1 and 2 years following BMT. Such a difference
      disappeared at 3 years after BMT, because of the late decrease in growth rate in
      patients given TBI and chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262473
TI  - Bone mineral density in children and adolescent females treated with high doses
      of L-thyroxine.
AB  - Single-photon absorptiometry was used to assess forearm bone mineral content
      (BMC) at a proximal site (PBMC) and at a more distal site (DBMC) of the non
      dominant distal forearm in 20 children and adolescent females taking high doses
      of L-thyroxine (120 micrograms/m2/day) for a period of 6-96 months for endemic
      goiter, Hashimoto's thyroiditis or thyroid cancer. PBMC was significantly reduced
      compared to controls (p < 0.002). No correlation was found between PBMC, the
      values of circulating thyroid hormones and the indices of tissue hyperthyroidism
      such as TSH and systolic time intervals (STI), suggesting that bone is a very
      sensitive target for thyroid hormones. Further studies are necessary to confirm
      our findings and to verify their clinical significance. At present, we believe
      that suppressive doses of L-thyroxine should be reserved for cancer patients
      only.

PMID- 8262474
TI  - Effect of small doses of iodine on thyroid function during caloric restriction in
      normal subjects.
AB  - It is well recognized that starvation and malnutrition are associated with a low
      T3 syndrome in man. A similar condition has been observed after intake of a low
      carbohydrate hypocaloric diet. However, little is known about the influence of
      iodine on these conditions. Therefore, we evaluated the effect of iodine
      supplementation on thyroid function before and after a short-term intake of a low
      carbohydrate diet in normal subjects residing in an iodine-deficient area. The
      study was performed in 16 young euthyroid, nonobese volunteers (11 males, 5
      females). The subjects were placed on a low carbohydrate (800 kcal) diet for 4
      days. Eight subjects received 500 micrograms iodine (oral) daily beginning 4
      weeks before diet. The control group (n = 8) received no iodine. After iodine
      supplementation, iodine excretion increased from 52 to 405 micrograms iodine/g of
      creatinine. Total T4 showed a slight but significant increase (104.2 nmol/l vs.
      115.8 micrograms/dl; p < 0.001); fT4 was unchanged. The intake of the hypocaloric
      low carbohydrate diet resulted in a striking decrease in both total and free T3
      and an increase of rT3 irrespective of iodine supplementation. T4 and fT4 were
      not affected in either group. During diet, iodine administration resulted in a
      decrease of basal TSH from 2.3 to 1.2 mU/l (p < 0.05), delta TSH from 10.3 to 4.5
      mU/l (p < 0.01) and delta T3 (T3 180 min after TRH) from 0.7 to 0.3 nmol/l (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262475
TI  - Cardiff puerperal mood and hormone study. 1. Saliva steroid hormone profiles in
      late pregnancy and the puerperium: endocrine factors and parturition.
AB  - Participants were 120 primiparous women who had vaginal delivery of a non
      handicapped child. Saliva was collected twice daily through parturition to day 35
      post-partum. In the prepartum, a highly significant circadian rhythm was seen in
      cortisol, with a lower-amplitude rhythm in progesterone (AM/PM = 1.12). Evening
      samples showed a rise in cortisol, with a highly significant rise on day -1. The
      rise was small. The fall in progesterone in the 3 days before parturition was
      also small (approximately 6%). Neither change provides an obvious trigger for
      parturition.

PMID- 8262476
TI  - Suppression by calcium of serum levels of intact parathyroid hormone in patients
      with primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (pHPT) is associated with a right-shifted relation
      between parathyroid hormone (PTH) secretion and calcium. However, it is also
      possible that a decreased suppressibility of PTH secretion by calcium is
      important for maintaining hypercalcemia in pHPT. We therefore compared the
      suppression of serum levels of intact PTH induced by a 1.5-gram oral calcium load
      in patients with mild pHPT with that in healthy subjects. The calcemic response
      to the oral calcium load was the same in the two groups and did not correlate
      with the degree of PTH suppression or to serum levels of vitamin D metabolites.
      It was found that serum levels of intact PTH were less suppressed by the oral
      calcium load in patients than in healthy subjects (p < 0.01), but with a
      considerable overlap between the two groups. The suppression of serum levels of
      intact PTH was correlated both to baseline serum total calcium levels (r = -0.55;
      p < 0.05) and osteocalcin levels (r = -0.69; p < 0.05) in the patients, but no
      such correlations were seen in the controls. We conclude that patients with pHPT
      have a decreased suppressibility of PTH secretion by calcium. Although this
      reduced suppressibility could be important for maintaining hypercalcemia in some
      patients with pHPT, it does not aid in the differential diagnosis between
      patients with mild pHPT and healthy subjects.

PMID- 8262477
TI  - Transient pseudohypoaldosteronism in obstructive renal disease with transient
      reduction of lymphocytic aldosterone receptors. Results in two affected infants.
AB  - We report two patients with transient pseudohypoaldosteronism due to obstructive
      renal disease. Both patients presented with a salt-losing episode simulating
      adrenal insufficiency. In one patient, transient reduction of aldosterone
      receptors could be documented, while in the second patient the clinical and
      biochemical parameters were consistent with transient pseudohypoaldosteronism.
      Aldosterone receptors were normal in both patients when studied after the
      surgical correction of the obstruction.

PMID- 8262478
TI  - Age-related change in plasma aldosterone response to exogenous angiotensin II in
      the rat.
AB  - Age-related changes in aldosterone response of the adrenal cortex to exogenous
      angiotensin II were studied in old compared to adult Long-Evans female rats. All
      animals were pretreated with dexamethasone and captopril and anesthetized with
      pentobarbital. Continuous infusion of angiotensin II (20 and 300 ng/min per 100 g
      body weight) for 20 and 30 min markedly enhanced the plasma concentration of
      aldosterone; however, the plasma aldosterone incremental response was
      significantly lower (-66.8% after the highest dose of angiotensin II) in old than
      in adult rats. These results, the first in the rat, suggest that the previously
      reported diminished aldosterone secretion is, at least in part, due to an
      impaired aldosterone biosynthesis capacity of the adrenal glomerular cells in
      response to angiotensin II.

PMID- 8262479
TI  - Relationship between the level of c-myc mRNA and histologic aggressiveness in
      thyroid tumors.
AB  - We investigated the relationship between the level of c-myc mRNA and histologic
      aggressiveness in thyroid tumors obtained at surgery. In thyroid carcinomas,
      there was a positive correlation between these two parameters, while in benign
      tumors there was no correlation between cellularity and the expression of the
      proto-oncogene c-myc. These results might be useful in the prognosis of thyroid
      tumors and consequently helpful in the management of the patient.

PMID- 8262481
TI  - International Symposium Frontiers of Paediatric Neuroendocrinology. London, 6-8
      September 1993. Abstracts.

PMID- 8262480
TI  - Calcitonin: from the determination of circulating levels in various physiological
      and pathological conditions to the demonstration of lymphocyte receptors.
AB  - This article summarizes our main findings concerning calcitonin (CT) physiology
      and pathology. We have devised a simple extraction method of circulating CT that
      much improves assay sensitivity and specificity for the measurement of the CT
      monomer. Combining this extraction method with newer immunometric assays permits
      a sensitive and exclusive measurement of monomeric CT. CT secretory capacity is 4
      5 times lower in women than in men, but there is no significant fall in basal or
      calcium-stimulated CT levels with age. We also found no evidence for CT
      deficiency in postmenopausal osteoporosis. On the contrary, changes in
      circulating CT levels appear to be secondary to the changes in bone turnover,
      whether in postmenopausal osteoporosis, after estrogen replacement therapy or in
      renal stone formers. We found a marked CT deficiency after thyroidectomy,
      radioactive iodine treatment and in patients with congenital hypothyroidism or
      autoimmune primary hypothyroidism. The deleterious effects of CT deficiency on
      bone mass remain, however, essentially speculative. Lastly, we have found
      specific and high-affinity CT receptors on normal circulating T-lymphocytes.
      Their meaning remains to be demonstrated but we have recently found that the
      osteolytic cytokines IL-1 and IL-6 are able to markedly reduce the number of CT
      receptors on T-lymphocytes without changing their affinity.

PMID- 8262482
TI  - Safety of human growth hormone therapy.

PMID- 8262483
TI  - Human pituitary growth hormone and Creutzfeldt-Jakob disease.

PMID- 8262484
TI  - Does growth hormone increase the risk of malignancies?

PMID- 8262485
TI  - In vivo metabolic defects in non-insulin-dependent diabetes mellitus.
AB  - In patients with non-insulin-dependent diabetes mellitus (NIDDM) alterations in
      insulin secretion and insulin action coexist, and create and sustain
      hyperglycaemia, which results from an imbalance between glucose production and
      glucose utilization. The target organs for insulin action are the liver
      (restriction of glucose production), the muscle (acceleration of glucose
      disposal) and the adipose tissue (inhibition of free fatty acid mobilization). In
      NIDDM, the liver produces an inordinate amount of glucose, secondary to an
      acceleration of gluconeogenesis, and is insensitive to the inhibitory action of
      insulin on glucose production. In NIDDM, skeletal muscle takes up less glucose in
      response to hyperinsulinaemia. Adipose tissue mobilizes a larger amount of free
      fatty acid, thereby possibly enhancing glucose production in the liver (Randle's
      cycle of metabolic competition between free fatty acids and glucose). Thus, the
      in vivo assessment of insulin action in NIDDM reveals a web of possibly
      interrelated metabolic defects, which in association with impaired insulin
      secretion cause a permanent, profound disruption of glucose homoeostasis.

PMID- 8262486
TI  - Syndrome X.
AB  - Using cross-sectional and longitudinal analysis of data from the San Antonio
      Heart Study, syndrome X (primary insulin resistance syndrome) has been redefined
      in terms of hyperinsulinaemia combined with changes in glucose tolerance, lipid
      pattern, blood pressure and body fat distribution. Syndrome X is itself an
      atherogenic cardiovascular risk factor, which interacts with environmental and
      genetic factors to lead to the eventual development of the endpoint of
      cardiovascular disease.

PMID- 8262487
TI  - Insulin-resistant syndromes in children.
AB  - Puberty is normally associated with a decline in tissue sensitivity to insulin.
      However, normal glucose homoeostasis is maintained by compensatory increases in
      glucose-stimulated insulin secretion. Here we describe studies performed in
      healthy children which have determined the site of insulin resistance (hepatic
      vs. peripheral) and whether this resistance extends to other substrates such as
      amino acid and free fatty acid metabolism. The changes in insulin action and
      secretion that are normally seen during puberty lead us to question the role of
      insulin resistance in other childhood conditions that are complicated by the
      later development of type I or type II diabetes, namely thalassaemia major and
      Turner's syndrome. These studies showed that in patients with thalassaemia and
      Turner's syndrome, insulin resistance and increased insulin secretion are very
      early metabolic defects that appear before the development of diabetes.

PMID- 8262488
TI  - Anthropometry in adolescence--secular trends, adoption, ethnic and environmental
      differences.
AB  - A secular trend towards higher final height and earlier pubertal maturation is
      seen in countries with favourable socio-economic development and higher social
      classes in countries are also associated with taller height and earlier
      maturation. Environmental factors, such as nutrition and infections, appear to be
      the main causes for differences in growth and maturation between ethnic and
      social groups. Differences in final height are mainly due to prepubertal growth.
      Studies on immigrant children and children adopted into privileged conditions
      from developing countries confirm the influence of early growth on subsequent
      growth. Catch-up growth in adopted children could only partially compensate for
      early stunting, and in several cases was cut short by early pubertal development.
      A minority developed very early puberty and eventually very short final height.
      The optimal rate of catch-up growth, the trigger mechanism for early puberty, and
      the effect of various types of nutritional intervention need to be studied. The
      studies reported here indicate the critical importance of optimal intra-uterine,
      infant and childhood growth as a basis for satisfactory growth during
      adolescence.

PMID- 8262489
TI  - Body composition during adolescence: methods, limitations and determinants.
AB  - To some extent body composition reflects nutritional status. It is also
      influenced by age, sex, race, physical activity and disease. The method used to
      measure body composition depends on the variable to be quantified. It may also
      depend on the practical conditions of the study. Detailed methods, such as
      densitometry, isotope dilution and electrical impedance give more accurate
      information, but they are commonly based on hypotheses established in adults.
      Anthropometric measurements can be used directly or as ratio or regression
      equations. At adolescence, the weight/height or body mass index (BMI) is
      preferred to weight for height as age is taken into account. In addition, the BMI
      pattern reflects real changes in body shape, and early in life it is an indicator
      of later development. In addition to measuring weight and height skinfold (SF)
      measurements should be carried out. The triceps SF is usually recommended and
      widely used as it is better than the subscapular SF to predict percent body fat.
      Trunk SFs, such as the subscapular, are better than extremity SF for their
      association with internal fat and their good correlations with risk factors and
      response to nutritional interventions. Chemical changes in the body are observed
      during growth. Chemical maturity does not occur until after puberty, but most
      changes occur early in life. Tracking is the maintenance of an individual in the
      same percentile range across age and varies according to the growth parameter and
      to the period of growth. Low tracking of fatness (up to the age of 8 years)
      corresponds to the period of rapid chemical changes. Low tracking of stature is
      observed at adolescence when height velocity is high. Nutrition affects fatness
      and stature, but the consequences of under- and over-nutrition differ between
      early childhood and adolescence. BMI curves show that most changes have their
      origin during the first years of life.

PMID- 8262490
TI  - The evolution of stature in humans.
AB  - There is significant evidence that a positive secular trend, apparently due to
      improved socioeconomic conditions, has led to taller stature today compared with
      150-200 years ago. However, study of fossil remains of our hominid ancestors
      demonstrates the stature of individuals living during the last million years
      reached the range of heights seen today. Furthermore, data from recent prehistory
      and the last 2,000 years also reveal adult height in many groups to be equal to
      modern humans of the same region. Optimal conditions for growth appear to predate
      the advent of modern civilization and public health measures.

PMID- 8262491
TI  - Catch-up growth during adolescence.
AB  - Various chronic diseases and malnutrition cause growth failure in childhood and
      adolescence; following recovery, catch-up growth may occur. The extent to which
      growth failure can be compensated for depends on the timing, severity and
      duration of the growth failure, as well as on the aetiology and pathogenesis of
      the disease restricting growth and development. There are three types of catch-up
      growth. In type 1, when growth restriction ceases, growth occurs to such an
      extent that the height deficit is rapidly eliminated. Once the original growth
      curve is attained, growth proceeds normally. In type 2, when growth restriction
      ceases, there is a delay in growth and somatic development. However, growth
      continues for longer than usual, compensating for the growth arrest. Type 3 is a
      mixture of types 1 and 2, and all three types may be complete or incomplete. Two
      factors make it difficult to record catch-up growth during adolescence: the large
      variability in timing, expression and duration of pubertal growth and somatic
      development, and the relationship between the measurement error and the increase
      in growth observed within a defined time period. To avoid data collection and
      analysis problems, prospective and long-term study design should be considered.
      Ideally, data collection should be started in the prepubertal period and continue
      until final adult height is reached. High technical standards and well-trained
      personnel should be used. A variety of parameters should be assessed to obtain
      different dimensions of the growth process and pubertal development.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8262492
TI  - Functional consequences from varying patterns of growth and maturation during
      adolescence.
AB  - Measurement of the growth of children among different populations has been
      important in assessing health and nutritional status. It is also useful in
      predicting functional consequences and long-term outcomes in the adult
      population. Childhood and adolescent growth patterns have been related to life
      expectancy as well as to the development of specific diseases such as coronary
      heart disease, diabetes and cancer (breast, ovary, prostate and pancreas).
      Childhood and adolescent growth has also been indirectly related to adult
      obesity. While these indirect observations do not suggest strategies for clinical
      intervention during childhood, they provide a framework for considerations of the
      influence of adolescent growth and maturation on the risk of chronic diseases,
      and for the application of anthropometry to research on diet and chronic disease.

PMID- 8262493
TI  - Maternal growth during pregnancy and lactation.
AB  - Until recently, it was widely accepted that the small amount of statural growth
      observed in young gravidas was unlikely to be clinically significant, to alter
      maternal nutritional status, or to threaten fetal growth. We show that this
      belief reflects incomplete information about growth and the use of inappropriate
      measuring techniques by investigators. We have done this using illustrations
      drawn primarily from the Camden Study, a controlled, prospective study of
      nutrition and growth during adolescent pregnancy. Maternal growth during
      pregnancy is prevalent and associated with increased gestational weight gain. In
      the postpartum period it is associated with increased triceps skinfolds, arm fat
      area and weight retention, all of which occur at caloric intakes comparable with
      those of pregnant, non-growing adolescents and mature women. Unlike pregnancy
      where research is continuing, the sequelae of maternal growth during lactation
      are virtually unstudied.

PMID- 8262494
TI  - Introduction to the use and interpretation of anthropometry in adolescence.

PMID- 8262495
TI  - Mechanisms of appetite control and their abnormalities in obese patients.
AB  - Human appetite is a complex mixture of physiological and psychological phenomena
      which include feelings of hunger, total energy intake, ingestion of particular
      nutrients, distribution and sizes of meals and snacks, specific cravings and food
      preferences. These phenomena can be assembled into a profile of motivation and a
      pattern of eating which represents the way in which appetite fluctuates over
      time. The satiety cascade shows the processes through which nutrition exerts
      effects on the biological system and, therefore, on feelings and behaviour.
      Within the biological system, the control of appetite involves post-ingestive
      mechanisms, including signals arising from the gastrointestinal tract and the
      release of hormones when food is processed. Post-absorptive mechanisms include
      the detection of important products of digestion, such as glucose and amino
      acids, together with the nature of the fuel mix oxidized and other metabolic
      variables. In obese patients, evidence points to a defect in the control of fat
      intake. In these people, dietary fat exerts only a weak action on satiation and
      satiety; it fails to generate strong responses in the mechanisms of the satiety
      cascade. An imbalance between fat intake and oxidation favours weight gain. A
      consideration of the psychobiological system (interactions between behaviour,
      peripheral physiology and neurochemical profiles) suggests strategies for
      treating or preventing the development of weight gain in vulnerable individuals.

PMID- 8262496
TI  - Energy metabolism and obesity in childhood.
AB  - Obesity in childhood often leads to obesity in adulthood, with the resulting
      potential risks to health. It has been suggested that in some cases, obesity
      develops because of a reduction in energy expenditure rather than excessive
      energy intake. While it is possible that this mechanism contributes to the
      development of obesity in specific cases, there is little evidence to suggest
      that it is an important contributory factor in the general population.

PMID- 8262497
TI  - Endocrine-metabolic pattern and adipose tissue distribution.
AB  - The associations between cardiovascular disease (CVD), non-insulin-dependent
      diabetes mellitus (NIDDM) and abdominal fat distribution are well established.
      The most important adipose tissue depot in this context is probably the mass of
      intra-abdominal adipose tissue which has been found to be associated with CVD,
      NIDDM and their established metabolic risk factors. This type of adipose tissue
      distribution is also associated with multiple endocrine aberrations, probably
      comprising an increased responsiveness of the hypothalamo-adrenal axis and a
      parallel or secondary decreased activity of the hypothalamic-gonadal axis.
      Epidemiological studies in both men and women indicate that this may be a
      consequence of psychological stress. Recently, indirect evidence for decreased
      production of growth hormone in this condition has also been recognized. These
      multiple and interrelated abnormalities comprise a syndrome where the primary
      disturbance could be localized to the hypothalamus and the main peripheral
      consequences would be metabolic effects on the mass and function of intra
      abdominal adipose tissue. This in turn, probably by the effects of elevated
      concentrations of portal free fatty acid levels on the liver, could result in
      insulin resistance and other metabolic risk factors known to be strongly
      associated with CVD and NIDDM.

PMID- 8262498
TI  - Therapeutic strategies in childhood obesity.
AB  - Childhood obesity leads to approximately 30% of adult obesity. However, the
      natural history of childhood obesity that persists into adulthood suggests that
      the obese child who becomes an obese adult will have more severe adult obesity
      than adults whose obesity began in adulthood. Therefore, to the extent that the
      severity of obesity predicts morbidity, persistence of childhood obesity may be
      expected to account for a disproportionate share of the adult sequelae of
      obesity. Fifty-year follow-up studies of a cohort with adolescent obesity have
      demonstrated that the mortality and morbidity of cardiovascular disease was
      significantly increased compared with a cohort that was lean throughout
      adolescence. Furthermore, the effect of adolescent obesity on adult morbidity and
      mortality appeared independent of the effects of adolescent obesity on adult
      weight status. Because truncal fat is deposited during adolescence, adolescent
      onset obesity may entrain both adult obesity and the effects of adolescent onset
      obesity on mortality and morbidity. These observations suggest that successful
      treatment of childhood and adolescent obesity is an effective approach to the
      prevention of severe adult disease. Recently, follow-up of children treated with
      diet, exercise and behaviour modification showed significantly lower weights 10
      years later than children treated in other ways (p < 0.01). These and other
      family-based treatments appear to be the most appropriate approaches to the
      treatment of childhood obesity. However, the prevalence of childhood and
      adolescent obesity suggests that even the most successful treatment may be of
      limited benefit if it relies on the traditional medical model (doctor/patient
      interaction).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262499
TI  - Assessment of growth and maturation during adolescence.
AB  - Clinical techniques currently used to assess adolescent growth and maturation are
      critically assessed with regard to anthropometric dimensions, measurement
      reliability, maturity indicators, and growth standards. While anthropometric
      measurements are virtually standardized throughout the world, a choice of
      techniques is available for the assessment of skeletal maturity, dental maturity
      and secondary sexual development. In addition, a variety of charts of
      international and national reference data are available for the comparison of
      individuals and groups. These assessment and comparison techniques are contrasted
      and compared to arrive at a scientifically appropriate set of recommendations for
      the clinical assessment of growth and maturity during adolescence.

PMID- 8262500
TI  - Plagiarism and scientific communication: a cautionary note.

PMID- 8262501
TI  - Population genetics and structure of Buryats from the Lake Baikal Region of
      Siberia.
AB  - Genetic polymorphisms of blood groups, serum proteins, red cell enzymes, PTC
      tasting, and cerumen types are reported for five Mongoloid populations of Buryats
      from the Lake Baikal region of Siberia (Russia). These groups are characterized
      by relatively high frequencies of alleles ABO*B, RH*D, cerumen D, GC*1F, ACP1*B,
      ESD*2, and PGD*C. Significant genetic heterogeneity between populations was
      demonstrated for the loci RH, MN, cerumen, PGD, ABO, GC, GLO, TF, and PGM1.
      Genetic distance analyses using five loci revealed a lower level of genetic
      microdifferentiation within the Buryat populations compared with other native
      Siberian groups. The distribution of gene markers in Buryats is similar to that
      found in neighboring Central Asian groups, such as the Yakuts and the Mongols.
      Intrapopulational analyses of the five Buryat subdivisions, based on R matrix and
      rii, indicate that one of the subdivisions is reproductively more isolated than
      the others and that two of the communities have received considerable gene flow.
      A nonlinear relationship was demonstrated between geographic and genetic
      distances of Buryat population subdivisions.

PMID- 8262502
TI  - Population relationships of Lapps as reflected by quantitative dermatoglyphics.
AB  - Relationships and divergence among five Lapp samples were assessed using finger
      and palm interdigital ridge counts. Lapp relationships to other Uralic speakers
      were also assessed. Multivariate minimum FST values expressing differentiation
      among Lapps are 0.012. These values are higher than those for most European
      populations and show the importance of isolation and genetic drift in Lapp
      populations. Skolt Lapps and Lapps of the Kola Peninsula are generally more
      similar to each other and are differentiated from Mountain and Fisher Lapps. When
      Lapps are placed within the context of Uralic speakers in general, they show a
      marked affinity for the Finnic speakers and are differentiated from the Samoyedic
      speakers of Siberia. The ridge counts support the hypothesis of a European origin
      for the Lapps.

PMID- 8262503
TI  - Multivariate approach to matrimonial mobility in Catalonia.
AB  - Matrimonial mobility in Catalonia was studied using 1986 census data. Comarca (a
      geographic division) of birth was used as the population unit, and a measure of
      affinity (a statistical distance) between comarques in spouse geographic origin
      was defined. This distance was analyzed with multivariate methods drawn from
      numerical taxonomy to detect any discontinuities in matrimonial mobility and gene
      flow between comarques. Results show a three-level pattern of gene flow in
      Catalonia: (1) a strong endogamy within comarques; (2) a 100-km matrimonial
      circle around every comarca; and (3) the capital, Barcelona, which attracts
      migrants from all over Catalonia. The regionalization in matrimonial mobility
      follows the geographically clear-cut groups of comarques almost exactly.

PMID- 8262504
TI  - Inbreeding patterns in the Basque Country (Alava Province, 1831-1980).
AB  - A considerable number of studies have shown that Spain is one of the countries on
      the European continent with a high level of inbreeding and that, in general, this
      level decreased more quickly and later than the levels in the rest of Europe. The
      types and frequencies of consanguineous marriages (up to third cousins), the mean
      inbreeding coefficient, and secular trends have been studied within the Basque
      Country (Alava Province) using information from ecclesiastic dispensations from
      1831 to 1980. A total of 5583 consanguineous marriages were registered in Alava
      over the whole period (150 years), and 79 different categories of relationship
      were observed. The analysis of the structure of consanguinity has shown some
      appreciable levels of close consanguineous unions: 0.08% (uncle-niece or aunt
      nephew marriages) and 0.96% (first-cousin marriages) of the total number of
      marriages. This seems to be a common phenomenon among provinces of northern
      Spain. The rates of total consanguinity and the mean coefficient of inbreeding in
      the population of Alava from 1861 to 1980 were 4.62% and 0.00124, respectively.
      The temporal trend pattern of inbreeding in Alava closely fits the pattern
      observed in other large European populations: France, Italy, and Belgium. This
      early fall in the level of inbreeding in Alava compared to the levels found in
      both large and small populations in central and western Spain might be due to the
      early industrial development of the Basque Country and the resulting loss of
      importance of landownership.

PMID- 8262505
TI  - Subcutaneous fat distribution in adolescents.
AB  - Sibling resemblance in fatness and subcutaneous fat distribution is addressed in
      a sample of healthy adolescents who belong to 122 nuclear families. Relative
      fatness and fat distribution were estimated using anthropometric measurements,
      bioelectric impedance, and ultrasound images. The patterns of fat distribution
      were defined by indexes constructed using combinations of subcutaneous fat
      measurements. Adjusted Z scores were used to analyze age- and sex-related changes
      on fatness and fat distribution. An analysis of variance was used to calculate
      the resemblance within and between families. The results show that there is
      significant family resemblance for the level of fatness. There is also
      significant resemblance between sibs of like sex for the fat distribution
      patterns. The results also show that subcutaneous fat thickness has a strong
      genetic component (60-65% of the variance) and that the patterns of fat
      distribution are apparent from early adolescence.

PMID- 8262506
TI  - Age of marriage and length of the first birth interval in a traditional Indian
      society: life table and hazards model analysis.
AB  - The length of the first birth interval is one of the strongest and most
      persistent factors affecting fertility in noncontracepting populations, with
      longer intervals usually associated with lower fertility. Compared to Western
      society, the average length of the first birth interval is much longer in
      traditional Indian society. Yet Indian fertility rates are higher because of
      either ineffective family planning procedures or deliberate nonuse of birth
      control and because of the high proportion of the population that is married.
      Here, we examine the effects of various sociodemographic covariates (with an
      emphasis on the role of age at marriage) on the length of the first birth
      interval for two states of India: Assam and Uttar Pradesh. Life table and
      multivariate hazards modeling techniques are applied to the data. Covariates such
      as age at marriage, present age of mother, female's occupation, family income,
      and place of residence have strong effects on the variation of the length of the
      first birth interval. For each subgroup of females (classified according to
      different levels of the covariates), the median length of the first birth
      interval for the Assam (Bengali-speaking) sample is shorter than that of the
      Uttar Pradesh (Hindi-speaking) sample.

PMID- 8262507
TI  - Comparative study of craniofacial morphology in Japanese and Australian
      aboriginal populations.
AB  - A metric study of 71 Japanese and 106 Australian aboriginal precontemporary
      crania was undertaken using direct measurements and cephalograms. Compared with
      Australian aboriginals, the Japanese are characterized by smaller cranial length,
      cranial base length, nasal floor length, palatal length, mandibular dimensions
      (except symphysis height), facial depth, posterior face height, and facial
      profile angle and larger cranial breadth and height, maxillary breadth, palatal
      breadth, anterior face height, and occlusal and mandibular plane angles. These
      differences confirm the previously described brachycephalic tendency in
      aboriginals and the dolichocephalic form in the Japanese. The differences are
      also consistent with the expected functional differences between the Australian
      aboriginal hunter-gatherer group masticating more resistant food with larger,
      more anteriorly located, more powerful masseter muscles and the Japanese group
      masticating less resistant food with correspondingly less robust masticatory
      musculature. The results highlight the differences in craniofacial morphology
      between groups with different genetic backgrounds subjected to significantly
      different environmental influences.

PMID- 8262508
TI  - Y-chromosome-specific haplotype diversity in Ashkenazic and Sephardic Jews.
AB  - DNA samples from Ashkenazic and Sephardic Jews were studied with Y-chromosome
      specific DNA probes p49f and p49a to screen for RFLPs and haplotypes. All 16
      European haplotypes were found in Jews, but only 2 of them (VII and VIII) were
      widespread. Haplotype distributions in the two Jewish populations are similar,
      but haplotypes XI and XV are more frequent in the Ashkenazim and haplotypes IV
      and V are more frequent in the Sephardim, indicating their origins.

PMID- 8262509
TI  - Changes in disease patterns in the Western Pacific and Southeast Asia.

PMID- 8262510
TI  - A strategy for the characterization of minute chromosome rearrangements using
      multiple color fluorescence in situ hybridization with chromosome-specific DNA
      libraries and YAC clones.
AB  - The identification of marker chromosomes in clinical and tumor cytogenetics by
      chromosome banding analysis can create problems. In this study, we present a
      strategy to define minute chromosomal rearrangements by multicolor fluorescence
      in situ hybridization (FISH) with "whole chromosome painting" probes derived from
      chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR)
      products of various region-specific yeast artificial chromosome (YAC) clones. To
      demonstrate the usefulness of this strategy for the characterization of
      chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker
      chromosome with two extra bands present in the karyotype of a child with multiple
      anomalies, malformations, and severe mental retardation was investigated. A
      series of seven-color FISH experiments with sets of fluorochrome-labeled DNA
      library probes from flow-sorted chromosomes demonstrated that the additional
      segment on 8p+ was derived from chromosome 6. For a more detailed
      characterization of the marker chromosome, three-color FISH experiments with
      library probes specific to chromosomes 6 and 8 were performed in combination with
      newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and
      8p23. These experiments demonstrated a trisomy 6pter-->6p22 and a monosomy 8pter-
      >8p23 in the patient. The present limitations for a broad application of this
      strategy and its possible improvements are discussed.

PMID- 8262511
TI  - Topographic pattern of the rearrangement of the dystrophin gene in Japanese
      Duchenne muscular dystrophy.
AB  - To compare the frequency and distribution of rearrangements in the dystrophin
      gene in Duchenne muscular dystrophy (DMD) between Japanese DMD patients and those
      in North America and Europe, Southern blot analyses of the dystrophin gene were
      carried out in 88 probands classified as DMD. Gene rearrangements were found in
      61 (69%) subjects, and they were composed of partial gene deletions in 53 (60%)
      probands and partial duplications in 7 (8%) probands. A total deletion of the
      gene was found in 1 (1%) patient. Among 53 patients with deletions, 34 (64%) had
      breakpoints between introns 44 and 52 and 7 (13%) had breakpoints between introns
      2 and 11. Both the frequency and the distribution of gene rearrangements found in
      this study were similar to those reported in North America and Europe. These data
      suggest that there are no ethnic or racial differences in the frequency and
      distribution of rearrangements thought to be caused by similar mechanisms in the
      dystrophin gene in all human racial groupings.

PMID- 8262512
TI  - High degree of genetic polymorphism in apolipoprotein(a) associated with plasma
      lipoprotein(a) levels in Japanese and Chinese populations.
AB  - We have developed a sensitive, high-resolutin method for the analysis of the
      apolipoprotein(a) [apo(a)] isoforms using sodium dodecyl sulfate (SDS)
      agarose/gradient polyacrylamide gel electrophoresis. In an analysis of the
      genetic polymorphism of apo(a) isoforms and their relationship with plasma
      lipoprotein(a) [Lp(a)] levels in Japanese and Chinese, this method identified 25
      different apo(a) isoforms and detected one or two apo(a) isoforms in more than
      99.5% of the individuals tested. The apparent molecular weights of the apo(a)
      isoforms ranged from 370 kDa to 950 kDa, and 22 of the 25 different apo(a)
      isoforms had a higher molecular weight than of apo B-100. Studies on Japanese
      families confirmed the autosomal codominant segregation of apo(a) isoforms and
      the existence of a null allele at the apo(a) locus. The observed frequency
      distribution of apo(a) isoform phenotypes fit the expectations of the Hardy
      Weinberg equilibrium in both the Japanese and Chinese populations. Our data
      indicate the existence of at least 26 alleles, including a null allele, at the
      apo(a) locus. The frequency distribution patterns of the apo(a) isoform alleles
      in Japanese and Chinese were similar to each other and also similar to that of
      apo(a) gene sizes reported in Caucasian American individuals. The average
      heterozygosity at the apo(a) locus was 92% in Japanese and 93% in Chinese. A
      highly significant inverse correlation was observed between plasma Lp(a) levels
      and the size of apo(a) isoforms in both the Japanese (r = 0.677, P = 0.0001) and
      the Chinese (r = -0.703, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262513
TI  - Frequent occurrence of familial aggregations of high lipoprotein(a) levels
      associated with small apolipoprotein(a) isoforms.
AB  - School-age children with high lipoprotein(a) [Lp(a)] levels were screened and
      family studies were conducted to examine the relationship between high Lp(a)
      levels and apolipoprotein(a) [apo(a)] isoforms in families. All the probands from
      17 families had one of the A2 to A12 apo(a) isoforms, which are the smaller
      apo(a) isoforms of the 25 different isoforms thus far detected. The ratio of
      subjects with high plasma Lp(a) levels was 0.47 among the first-degree relatives.
      All 15 relatives with high plasma Lp(a) levels shared one of the small apo(a)
      isoforms with the proband in each family, while 16 of 17 relatives with normal
      Lp(a) levels did not. These data indicate the frequent occurrence of familial
      aggregations of high Lp(a) levels associated with one of the small apo(a)
      isoforms.

PMID- 8262514
TI  - Acute intermittent porphyria caused by a G to C mutation in exon 12 of the
      porphobilinogen deaminase gene that results in exon skipping.
AB  - Genomic DNA from a patient with acute intermittent porphyria were analyzed by the
      polymerase chain reaction (PCR)-direct sequencing method. The patient was
      heterozygote for a point mutation G to C at the last position of exon 12 of the
      porphobilinogen deaminase (PBG-D) gene. Analysis of the cDNA fragments amplified
      by PCR revealed that the patient has the abnormal PBG-D mRNA, which does not have
      exon 12 and exists in an approximately equal amount to the normal mRNA.

PMID- 8262515
TI  - Analysis of 6 VNTR loci by 'multiplex' PCR and automated fluorescent detection.
AB  - The polymerase chain reaction was used to amplify six small variable number of
      tandem repeat loci in two reactions (D19S20 co-amplifying with D17S5 and D1S80;
      D17S766 co-amplifying with D16S83 and D17S24). When coupled with fluorescent
      detection of the products, this provides a rapid, highly discriminating automated
      test. Preferential amplification of small alleles, leading to 'allelic dropout'
      was found to occur in D19S20 and D16S83. Population databases are presented for
      Caucasians and Afro-Caribbeans at loci D19S20, D16S83 and D17S24, and for Asians
      at D19S20.

PMID- 8262516
TI  - Localization of the gene for human heart fatty acid binding protein to chromosome
      1p32-1p33.
AB  - Heart fatty acid binding protein (hFABP) is an abundant 14-kDa cytosolic protein
      thought to be involved in trafficking of fatty acids from the plasma membrane to
      sites of beta-oxidation in mitochondria and peroxisomes and to the endoplasmic
      reticulum for lipid synthesis. A human hFABP cDNA isolated by polymerase chain
      reaction was used as a probe for in situ hybridization to metaphase chromosomes.
      A fragment of the gene for human hFABP was used as a probe for fluorescence in
      situ hybridization to metaphase chromosomes. The cDNA and genomic probes both
      localized the gene for human hFABP to chromosome 1p32-1p33.

PMID- 8262517
TI  - Familial true hermaphroditism: paternal and maternal transmission of true
      hermaphroditism (46,XX) and XX maleness in the absence of Y-chromosomal
      sequences.
AB  - We report on 46,XX true hermaphroditism and 46,XX maleness coexisting in the same
      pedigree, with maternal as well as paternal transmission of the disorder.
      Molecular genetic analysis showed that both hermaphrodites as well as the 46,XX
      male were negative for Y-chromosomal sequences. Thus, this pedigree is highly
      informative and allows the following conclusions: first, the maternal as well as
      paternal transmission of the disorder allows the possibility of an autosomal
      dominant as well as an X-chromosomal dominant mode of inheritance; second,
      testicular determination in the absence of Y-specific sequences in familial 46,XX
      true hermaphrodites as well as in 46,XX males seems to be due to the varying
      expression of the same genetic defect; and third, there is incomplete penetrance
      of the defect.

PMID- 8262518
TI  - Somatic pairing of centromeres and short arms of chromosome 15 in the
      hematopoietic and lymphoid system.
AB  - Normal human bone marrow and peripheral blood leukocytes as well as malignant
      cells from a variety of leukemias and lymphomas, demonstrate somatic pairing of
      centromeres and p arms of chromosome 15 during interphase. This phenomenon,
      effected by sequences on the p arm and requiring the intranuclear transport of
      spatial domains for at least one of the homologs, was not seen in amniotic fluid
      cells, uterine cervical tissue or in tissue fibroblasts. These studies contribute
      to the recent evidence of somatic pairing of homologous chromosomes in man and
      provide support for mobile chromosomal domains in interphase. It appears that
      sequences on the p arm of chromosome 15, possibly the nucleolar organizing genes,
      are uniquely important in the maturation of benign and malignant cells of hemato
      lymphopoietic origin.

PMID- 8262519
TI  - Chromosomal localization of 9 KOX zinc finger genes: physical linkages suggest
      clustering of KOX genes on chromosomes 12, 16, and 19.
AB  - Nine KOX zinc finger genes were localized on four human chromosomes by in situ
      hybridization of cDNA probes to metaphase chromosomes. KOX1 (ZNF10), KOX11
      (ZNF18), and KOX12 (ZNF19) were mapped to chromosome bands 12q24.33, 17p13-p12,
      and 16q22-q23, respectively. Six other KOX genes were localized on chromosome 19:
      KOX6 (ZNF14) and KOX13 (ZNF20) to 19p13.3-p13.2, KOX5 (ZNF13) and KOX22 (ZNF27)
      to 19q13.2-qter, and KOX24 (ZNF28) and KOX28 (ZNF30) to 19q13.4. Pulsed field gel
      electrophoresis experiments showed that the pairs of KOX genes found on the
      chromosome bands 12q24.33, 16q22-q23, 19p13.3-p13.2, or 19q13.3-qter lie within
      200-300 kb DNA fragments. This suggests the existence of KOX gene clusters on
      these chromosomal bands.

PMID- 8262520
TI  - Logistic regression model to estimate the risk of unbalanced offspring in
      reciprocal translocations.
AB  - The aim of this study was to estimate the risk of viable unbalanced offspring for
      a parental carrier of reciprocal translocation. On a large computerized database
      of reciprocal translocations we used logistic regression to model this risk. The
      status of the progeny is the outcome variable. Explanatory covariates are
      cytogenetic characteristics of the translocation, age and sex of the parental
      carrier, and potential viability of the gametes. The results obtained by the
      logistic model demonstrate the important role of certain variables such as the
      sex of the parental carrier and the R band length of the translocated segments.
      Within the group of lower risk (risk of viable unbalanced offspring less than
      5%), 97% of the individuals are correctly classified with this model. For this
      group, the choice prenatal diagnosis can be best discussed by considering both
      the risk for viable unbalanced offspring and the risk of induced abortion
      following prenatal diagnosis.

PMID- 8262521
TI  - von Hippel-Lindau disease: identification of deletion mutations by pulsed-field
      gel electrophoresis.
AB  - Von Hippel-Lindau disease (VHL) is an inherited multisystem neoplastic disorder.
      We prepared a 2.5-megabase (Mb) restriction map of the region surrounding the VHL
      gene and identified and characterized overlapping deletions in three unrelated
      patients affected with VHL. The smallest nested deletion (100 kb) was located
      within a 510-kb NruI fragment detected by 19-63'. The rearrangements detected
      will be useful in isolating and evaluating candidate cDNAs for the VHL gene. The
      detailed physical map will be useful in studying the organization and structure
      of genes in the VHL region.

PMID- 8262522
TI  - The human cytochrome b5 gene and two of its pseudogenes are located on
      chromosomes 18q23, 14q31-32.1 and 20p11.2, respectively.
AB  - Using very high stringency hybridization conditions for the Southern blot
      hybridization analysis of hamster-human cell hybrid DNA, we were able to map the
      human cytochrome b5 gene and two of its pseudogenes (psgb(5)1 and psgb(5)2)
      unambiguously to chromosomes 18, 14, and 20. These localizations were confirmed
      and extended to 18q23, 14q31-32.1, and 20p11.2 by using a combination of
      nonisotopic in situ hybridization of chromosomal spreads and the polymerase chain
      reaction analysis of DNA samples isolated from somatic cell hybrids retaining
      deletions or translocations of chromosome 18.

PMID- 8262523
TI  - Detection of a high mutation frequency in exon 12 of the porphobilinogen
      deaminase gene in patients with acute intermittent porphyria.
AB  - Direct cDNA sequencing was performed on asymmetrically amplified transcripts from
      the porphobilinogen deaminase (PBG-D) gene of thirteen unrelated individuals with
      acute intermittent porphyria. Four different mutations and a polymorphic site
      were detected in exon 12 of the gene, four being the result of single base
      substitutions and one being caused by dinucleotide deletion. All of these
      mutations are located in domain 3 of the PBG-D molecule, with the single base
      substitutions affecting the hydrophobic interfaces between domains 1 and 3. The
      dinucleotide deletion results in a frame-shift producing a premature stop codon.

PMID- 8262524
TI  - Generation of a chromosome-22-specific c-DNA library as confirmed by FISH
      analysis.
AB  - We have recently developed a strategy for the rapid enrichment of c-DNA fragments
      from selected human chromosomes. Heteronuclear RNA (hn-RNA) is isolated from a
      somatic cell hybrid that retains a single human chromosome in a rodent
      background. Following c-DNA synthesis, human sequences are selectively amplified
      by the Alu polymerase chain reaction (Alu-PCR). Here we have applied this
      protocol for the selective isolation of novel c-DNAs encoded by chromosome 22.
      Fluorescence in situ hybridization has been used to confirm the chromosome-22
      specific origin of the c-DNA fragments. Controls show DNAse-free RNase-treated hn
      RNA results in no c-DNAs or Alu-PCR products. As demonstrated by competitive in
      situ suppression hybridization (CISS), the majority of the Alu-PCR products from
      hybrid GM 10027 are located on chromosome 22. Without competition, hybridization
      signals have also been identified on other human chromosomes. These unspecific
      hybridization signals result from Alu sequences and can successfully be reduced
      by competition with cot 1 DNA. This is the first report of the use of CISS for
      the localization of chromosome-specific c-DNAs.

PMID- 8262525
TI  - Rapid detection of single nucleotide deletions: application to the beta 6 (-A)
      mutation of the beta-globin gene and to cystic fibrosis.
AB  - The formation of heteroduplexes from the amplified products of homologous alleles
      has been shown to be useful in the identification of heterozygotes carrying
      deletion or insertion mutations. Here, we describe an improved procedure that
      allows the detection of single base pair (bp) deletions on nondenaturing
      polyacrylamide gels. Carriers for a common Mediterranean beta-thalassemic
      mutation, beta6 (-A), could be easily detected by use of this method, as could
      carriers of a 1-bp deletion in the cystic fibrosis gene.

PMID- 8262526
TI  - Chromosomal assignment of the human smg GDP dissociation stimulator gene to human
      chromosome 4q21-q25.
AB  - The 3'-end of the cDNA encoding the smg GDP dissociation stimulator (smg GDS)
      protein shares 100% homology with the previously published expressed sequence tag
      00038 site. This site extends the 3'-end of the smg GDS gene by 212 bp. It has
      been localized to human chromosome 4. Here, we have refined the localization of
      smg GDP to human chromosome 4q21-q25 using a mapping panel of rodent/human
      somatic cell hybrids containing different parts of chromosome 4. This chromosomal
      localization of smg GDP to 4q21-25 overlaps with a region of allele loss in
      primary hepatocellular carcinoma (4q13-q26).

PMID- 8262527
TI  - A common exonic polymorphism in the human D5 dopamine receptor gene.

PMID- 8262528
TI  - A new polymorphism in the gene for GAP43.
AB  - A new polymorphism has been identified in the 3'-untranslated region of the gene
      for GAP43. It is present with a frequency of 0.327 in the Centre d'Etude du
      Polymorphisme Humaine (CEPH) parents and is slightly lower in Alzheimer's (0.269)
      and Parkinson's (0.231) patients.

PMID- 8262529
TI  - Sequence variability of the tetranucleotide repeat of the human beta-actin
      related pseudogene H-beta-Ac-psi-2 (ACTBP2) locus.
AB  - Sequence analysis of polymerase chain reaction (PCR) amplified products from the
      presumed tetranucleotide repeat at the human beta-actin related pseudogene H-beta
      Ac-psi-2 (ACTBP2) locus shows far greater variability in both PCR product length
      and sequence than has been previously reported. Alleles differing in size by 1 bp
      exist, and accurate sizing is required if the locus is to be used to its full
      potential.

PMID- 8262530
TI  - Oocyte selection model for the maternal age-dependence in Down syndrome.

PMID- 8262531
TI  - The relationship between meiotic chromosome pairing and chiasma formation.

PMID- 8262532
TI  - Estimating regional brain activity from evoked potential fields on the scalp.
AB  - Potential fields on the surface of the brain were estimated from discretely
      sampled scalp fields in human subjects. Relatively simple methods of linear
      algebra were combined with detailed anatomical information from magnetic
      resonance imaging. The method was verified using a tank model of the human head
      that encased a fully hydrated human skull in a polymer matrix of controlled
      resistivity matching that of human brain and scalp. Brain surface fields evoked
      by checkerboard contrast reversal, spread less than their scalp field
      counterparts, and provided information helpful in localizing brain activity.

PMID- 8262533
TI  - Method to reduce blur distortion from EEG's using a realistic head model.
AB  - A mathematical procedure, which we call "Deblurring," was developed to reduce
      spatial blur distortion of scalp-recorded brain potentials due to transmission
      through the skull and other tissues. Deblurring estimates potentials at the
      superficial cerebral cortical surface from EEG's recorded at the scalp using a
      finite element model of each subject's scalp, skull and cortical surface
      constructed from their magnetic resonance images (MRI's). Simulations indicate
      that Deblurring is numerically stable, while a comparison of deblurred data with
      a direct cortical recording from a neurosurgery patient suggests that the
      procedure is valid. Application of Deblurring to somatosensory evoked potential
      data recorded at 124 scalp sites suggests that the method produces a dramatic
      improvement in spatial detail, and merits further development.

PMID- 8262534
TI  - Simulation studies of multiple dipole neuromagnetic source localization: model
      order and limits of source resolution.
AB  - Numerical simulation studies were performed using a multiple dipole source model
      and a spherical approximation of the head to examine how the resolution of
      simultaneously active neuromagnetic sources depends upon: 1) source modeling
      assumptions (i.e., number of assumed dipoles); 2) actual source parameters (e.g.,
      location, orientation, and moment); and 3) measurement errors. Forward
      calculations were conducted for a series of source configurations in which the
      number of dipoles, specific dipole parameters, and noise levels were
      systematically varied. Simulated noisy field distributions were fit by multiple
      dipole models of increasing model order (1, 2, ..., 6 and alternative statistical
      approaches (i.e., percent of variance, reduced chi-square, and F-ratio) were
      compared for their effectiveness in determining adequate model order. Limits of
      spatial resolution were established for a variety of multi-source configurations
      and noise conditions. Implications for the analysis of empirical data are
      discussed.

PMID- 8262535
TI  - Stability and movement of a one-link neuromusculoskeletal sagittal arm.
AB  - This paper's focus is the stability, point-to-point, and rhythmic movements of a
      one-link sagittal arm. The system is highly nonlinear in all its physical and
      physiological attributes. The major physiological characteristics of this system
      are simultaneous activation of a pair of nonlinear muscle-like actuators for
      control purposes, existence of nonlinear spindle-like sensors, and actions of
      gravity and loading. Transmission delays are included in the afferent and
      efferent neural paths to account for a more accurate representation of the reflex
      loops. An algorithm for computation of the actuator forces and the feedback
      signals in the system is provided. It automatically renders positive forces and
      positive neural signals. The positiveness of the forces represents the
      unidirectional character of muscular forces, i.e., natural muscles can only pull
      in the direction of shortening. The positiveness of the neural signals implies
      these signals can correspond to firing rates. The stability of the system is
      analyzed. The role of the nonlinearities in the dynamics, actuators, and feedback
      signals, and the delays in the feedback loops in destabilizing the system, and
      the consequently undesirable oscillations are studied by simulation. The system
      is designed to perform stable point-to-point movement. The effects of the
      presetting of the input signals, gain of the feedback loops, and the duration of
      delays in generating undesirable tremor-like oscillations at the end of the
      movement are studied and demonstrated by digital computer simulations.

PMID- 8262536
TI  - Output space tracking control for above-knee prosthesis.
AB  - The control of a knee joint in an active above-knee prosthesis has been designed
      using the Lyapunov tracking method. A simulation of locomotion was done to prove
      that the tracking control in output space is a valuable real time control method
      for artificial legs. The data used for simulation was collected in able-bodied
      subjects while they walked on a powered treadmill. Human volunteers were braced
      with an ankle splint (limiting dorsi- and plantar flexion) and with a knee cage
      (limiting knee movements to the lateral plane). We studied the achieved tracking
      of the prescribed knee motion, deviations of the thigh movement from the
      prescribed trajectory, maximal angular deviations from the desired trajectory and
      the power consumption as functions of a limited maximal knee torque and a damping
      constant in the knee actuator. We found that the use of output tracking method is
      suitable for the design of appropriate hardware of an above-knee prosthesis and
      for real-time control.

PMID- 8262537
TI  - Operator error in a level coded myoelectric control channel.
AB  - Two forms of error exist in the level coded myoelectric control channel: system
      error and operator error. Currently in level coded (3-state) myoelectric
      prosthesis, target and switching level settings are optimized for the presence of
      system error only. In this study, system error was minimized in order to examine
      operator error. The magnitude of the operator error was found to exceed the
      magnitude of the experimental system error as well as the system error associated
      with a typical prosthesis control unit. These findings suggest that operator
      error should be considered when optimizing target levels and decision boundaries
      for level coded myoelectric prosthesis controllers. Since the operator response
      was estimated to be normally distributed, it is described by its mean and
      standard deviation. This information can be used to determine the desired optimal
      settings.

PMID- 8262538
TI  - Diffraction correction methods for insertion ultrasound attenuation estimation.
AB  - We describe diffraction effects in acoustic ultrasound attenuation coefficient
      estimation using an insertion technique. We characterize the estimation error
      produced by diffraction as a function of distance and nominal attenuation values.
      Two new methods for correcting for the diffraction effect are presented. They are
      termed the Theoretical Diffraction Correction (TDC) and Experimental Diffraction
      Correction (EDC) techniques, respectively. Experimental validation of the two
      techniques is also presented, using two different sets of ultrasound measurements
      obtained with 1 MHz and 500 kHz transducer pairs, respectively. Significant
      improvement in the accuracy of the acoustic attenuation coefficient is
      demonstrated using both techniques.

PMID- 8262539
TI  - Noninvasive acoustical detection of coronary artery disease: a comparative study
      of signal processing methods.
AB  - Previous studies have indicated heart sounds may contain information useful in
      the detection of occluded coronary arteries. During diastole, coronary blood flow
      is maximum, and the sounds associated with turbulent blood flow through partially
      occluded coronary arteries should be detectable. In order to detect such sounds,
      recordings of diastolic heart sound segments were analyzed by using four signal
      processing techniques; the Fast Fourier Transform (FFT), the Autoregressive (AR),
      the Autoregressive Moving Average (ARMA), and the Minimum-Norm (Eigen-vector)
      methods. To further enhance the diastolic heart sounds and reduce background
      noise, an Adaptive filter was used as a preprocessor. The power ratios of the FFT
      method and the poles of the AR, ARMA, and Eigen-vector methods were used to
      diagnose patients as diseased or normal arteries using a blind protocol without
      prior knowledge of the actual disease states of the patients to guard against
      human bias. Results showed that normal and abnormal records were correctly
      distinguished in 56 of 80 cases using the Fast Fourier Transform (FFT), in 63 of
      80 cases using the AR, in 62 of 80 cases using the ARMA method, and in 67 of 80
      cases using the Eigenvector method. Among all four methods, the Eigenvector
      methods showed the best diagnostic performance when compared with the FFT, AR,
      and ARMA methods. These results confirm that high frequency acoustic energy
      between 300 and 800 Hz is associated with coronary stenosis.

PMID- 8262540
TI  - Compressing data volume of left ventricular cineangiograms.
AB  - In this paper a method of compressing data volume for left ventricular
      cineangiograms is proposed. This method enables digital-optical discs to store
      the cineangiograms with an equivalent recording density to that of HDTV VTR's
      while preserving the quality of the original image. The data volume of the
      cineangiograms is compressed by approximating function and storing its
      coefficients. With this method, each cineangiogram frame is first decomposed into
      three regions: the inner part, the inner wall, and the background (using a
      statistical method previously reported by the authors). Each region is then
      compressed by means of a difference operation and an adaptive approximation with
      smooth functions. Performance is tested on 20 cases using actual cineangiograms.
      The specifications were verified for a spatial resolution of 1000 TV lines, a
      dynamic range of 60 dB, an SNR of 40 dB [pp/rms], volume compression to 7% of the
      original volume, and 0.19 [second/frame] for decoding on a 1.7 MFLOPS computer.

PMID- 8262541
TI  - Conductance volumetric model of an eccentrically positioned catheter within a
      three-compartment ellipsoidal ventricle.
AB  - This paper presents a mathematical model of the electric field generated and
      resistance measured by a conductance catheter within a three-compartment
      ellipsoidal approximation of a cardiac ventricle. The model is based on a novel
      combination of analytical and numerical techniques. The numerical component of
      the model predicts displacement of the catheter along the central longitudinal
      ventricular axis, as well as eccentric positions off that axis. The analytical
      component of the model enables interactive definition of model parameters during
      simulation. This versatile combination enables performance of validation studies
      that include simulations of various catheter movements within a ventricle of
      changing geometry. The results of our simulation studies agree with the results
      of previous investigators studying ex-vivo systems.

PMID- 8262542
TI  - Monitoring of electrocardiograms in bed without utilizing body surface
      electrodes.
AB  - We investigated a system by which an electrocardiogram can be obtained without
      the individual's awareness. The practice of this concept involves placing the
      electrodes in a bed set composed of electrically conductive textiles.
      Electrocardiograms were successfully obtained during sleep. However, during the
      periods of subject's movement in bed, the waveform became unrecognizable.

PMID- 8262543
TI  - On generalized photocurrent spectral moments and the recovery of speed
      distribution in laser Doppler flowmetry.
AB  - Laser Doppler flowmetry (LDF) is a noninvasive method to assess tissue blood
      flow. By calculating the first moment of the Doppler signal power spectral
      density, a real-time output is generated that scales linearly with the perfusion
      flux defined as the product of average speed and concentration of moving blood
      cells (MBC's) if multiple scattering is negligible. However, this first spectral
      moment alone is apparently deficient to provide further information about the
      MBC's under study and therefore unable to answer more intricate questions in LDF.
      Without assuming any specific MBC speed or scattering vector distribution, a
      generalized formula for photocurrent spectral moments is first derived in the
      case of low and moderate MBC concentration. Then as a direct and important use of
      the formula, the speed distribution of MBC's is obtained via Henyey-Greenstein
      phase function and a Fourier inversion. The important implications and
      applications of this formulation in extracting more MBC information are discussed
      together with some other related issues.

PMID- 8262544
TI  - Measurement of electrical activity of the human small intestine using surface
      electrodes.
AB  - Electrical activity of the human small intestine is usually measured by implanted
      or intraluminal electrodes. The application of these invasive techniques is,
      however, very limited. In this paper, a noninvasive technique is introduced to
      measure electrical activity of the small intestine by placing electrodes on the
      abdominal skin over the small intestine. Surface recordings were obtained in ten
      healthy volunteers, three patients with total gastrectomy and five patients with
      gastroparesis (a slight degree of paralysis of the mucosal coat of the stomach)
      with implanted electrodes on the serosa of the duodenum. An omnipresent 9-12 cpm
      electrical activity was observed in all surface recordings. Our findings from the
      surface electrodes were consistent with those reported in the literature via
      implanted or intubated electrodes. It is concluded that the technique described
      in this paper provides a noninvasive way to measure electrical activity of the
      small intestine. It may have potential application in medical research and
      clinical diagnosis.

PMID- 8262545
TI  - Classical pathway of complement activation in mammalian kidneys.
AB  - Two monoclonal antibodies (mAb M4d2 and M4d3) specific for the alpha 2-fragment
      (C4d), and one antibody (mAb M4c3) specific for the gamma-chain of human
      complement protein C4, have been tested for cross-reactivity against mammalian
      complement. These mAb have also been found to react with C4 from guinea-pig (mAb
      M4d2 and M4c3) as well as from cattle, baboon and rhesus monkey (mAb M4d3 and
      M4c3) in an activation ELISA. Since reactivity of mAb M4d2 and M4c3 included
      guinea-pig complement, the specific recognition of mammalian C4 could be
      confirmed with sera from C4-deficient (def') guinea-pigs. mAb M4d2 or M4d3, but
      not mAb M4c3, stained glomerular deposits within renal tissue sections from pig,
      cattle and guinea-pig. In the case of mAb M4d2, specificity of that staining
      could also be demonstrated in kidney specimens from C4-def' guinea-pigs. It can
      be concluded that, as in humans, the C4d fragment is also present in mammalian
      glomeruli. Compared with normal guinea-pigs, the C4-def' and C2-def' animals
      showed markedly increased glomerular deposits of IgM. It appears that glomerular
      deposition of complement C4d in mammals: (1) indicates activation via the
      classical pathway; (2) represents a general phenomenon of renal homeostasis; and
      (3) seems to be involved in the physiological clearance of immune complexes.

PMID- 8262547
TI  - Co-deposition of clusterin with the complement membrane attack complex in
      myocardial infarction.
AB  - Clusterin is a multi-functional plasma glycoprotein that has been shown to
      inhibit formation of the complement membrane attack complex (MAC) by preventing
      the association of terminal complement complexes with target cell membranes.
      Recent studies have suggested that complement activation is involved in the
      development of tissue injury of myocardial infarction. In this study we observed
      that clusterin is selectively deposited in the infarcted areas of human
      myocardium. Clusterin deposits were observed in the heart tissue of 10 patients
      whose infarcted lesions were 8 hr to 14 days old, but not in patients who died
      from other causes. Clusterin co-localized with the MAC on the surface of damaged
      cardiomyocytes. In normal myocardium only endothelial lining of blood vessels
      occasionally stained positive for clusterin. The 80,000 MW clusterin was also
      detected by Western blot analysis in extracts of myocardial infarction lesions,
      but only faintly in extracts of normal heart. As clusterin has apparently failed
      in protecting myocardium against complement-mediated cell injury its main role
      might be to participate in the clearance of damaged and necrotic tissue together
      with the MAC.

PMID- 8262546
TI  - Clonal variations in complement activation and deposition of C3b and C4b on model
      immune complexes.
AB  - This study examined the relationship between complement activation and the
      deposition of C3b and C4b on a panel of model immune complexes (IC). IC were
      constructed by combining murine monoclonal IgM, IgA, IgG1, IgG2a or IgG3 anti
      dinitrophenyl (DNP) antibodies with DNP-bovine serum albumin (DNP-BSA). The IC
      were incubated with human plasma as a complement source and the formation of C4a
      and C3a, as well as the deposition of C4b and C3b on the IC, measured by
      radioimmunoassay. The results indicate that there were isotype-independent
      variations in the capacity of different types of IC to activate the classical
      pathway, especially for isotype-matched pairs of IC containing IgG1, IgG2a and
      IgG3 antibodies. In most cases, there was a direct relationship between classical
      pathway activation and the cleavage of C3. There was, for most of the IC, a
      direct correlation between cleavage of C4 and C3 and the subsequent deposition of
      C4b and C3b on the IC. However, a pair of IC constructed with independently
      derived IgG1 antibodies was virtually identical with respect to C3 cleavage and
      yet differed in the number of C3b molecules deposited on the IC. Collectively,
      these data suggest that the immunoglobulin variable region can play a significant
      role in both complement activation and the deposition of C3b and C4b on IC.

PMID- 8262548
TI  - Naturally occurring anti-band 3 antibodies have a unique affinity for C3.
AB  - Naturally occurring anti-band 3 antibodies appear to mediate opsonization of
      oxidatively stressed and in vivo aged red cells. Their low concentration in
      plasma (< 100 ng/ml) and weak affinity (estimated association constant, 5-7 x
      10(6) l/mol) contrasted with their biological efficiency. In compensating for
      their inadequate properties they have an affinity for C3 at a site independent of
      the antigen binding domain, with an estimated association constant of 2-3 x 10(5)
      l/mol. Though weak, their binding to C3 was about 100 times higher than that of
      whole IgG, which is known to have an affinity for C3. The affinity for C3 may
      render these antibodies preferred targets of the short-lived nascent C3b and
      result in a preferential C3b-anti-band 3 complex formation. C3b-IgG complexes
      represent the best opsonins and can nucleate alternative complement pathway C3
      convertases by which opsonization is further enhanced.

PMID- 8262549
TI  - Presentation of peptides and proteins by intestinal epithelial cells.
AB  - Murine intestinal epithelial cells (IEC) constitutively express major
      histocompatibility complex (MHC) class II molecules, which enable them to present
      foreign antigens to T cells in vitro. In this study we have compared the ability
      of freshly isolated IEC and spleen adherent cells to present both protein and
      peptide antigens to T cells in vitro. Consistently IEC were unable to present
      protein but could readily present immunogenic peptides in an MHC-dependent
      fashion to stimulate lymphokine release from T cells. Consistent with their
      inability to process protein antigens, IEC were also unable to present a
      synthetic peptide which requires intracellular processing, whereas spleen antigen
      presenting cells (APC) could readily present the same peptide. These findings
      indicate that IEC may lack the necessary intracellular machinery to process
      exogenous antigens but they raise the possibility that IEC may play an important
      immunological role in vivo by presenting processed peptides to T cells.

PMID- 8262550
TI  - Protein kinase A-mediated phosphorylation of the T-cell surface antigen CD27.
AB  - CD27 is a T-cell surface antigen expressed on the majority of peripheral T cells
      and belongs to a newly defined receptor family including the low-affinity nerve
      growth factor receptor, tumour necrosis factor (TNF) receptors, the B-cell
      activation antigen CD40, and the Fas antigen. Although the function of CD27 has
      not been defined, several experimental observations support the notion that this
      molecule plays an important role in the process of T-cell activation. In this
      paper, we have demonstrated that a rapid hyperphosphorylation of CD27 is induced
      by a cyclic AMP-inducing agent, forskolin, and a membrane-permeable cAMP
      analogue, 8-bromo-cAMP, as well as phorbol 12-myristate 13-acetate (PMA). In
      addition, increased phosphorylation of CD27 in T-cell activation either via CD2
      or CD3 pathways was strongly suppressed by a cyclic nucleotide-dependent kinase
      inhibitor, H-8, but only slightly by a protein kinase C inhibitor, staurosporine.
      These results suggest that protein kinase A might be a key kinase responsible for
      CD27 phosphorylation in the process of T-cell activation. CD27 is the first T
      cell surface antigen demonstrated to be phosphorylated by the cyclic AMP-protein
      kinase A-mediated pathway.

PMID- 8262551
TI  - Intermediate- and high-affinity interleukin-2 receptors expressed in an IL-4
      dependent T-cell line induce different signals.
AB  - In order to understand the respective roles of IL-2R alpha and IL-2R beta
      subunits in transmission of the interleukin-2 (IL-2)-mediated growth signals, we
      have established two IL-4-dependent murine T-cell clones stably expressing the
      human IL-2R beta chain and three clones stably expressing the human IL-2R alpha
      chain. Whereas parental LD8 cells (which express only the murine IL-2R beta
      chain) do not proliferate in response to IL-2, cell lines stably expressing human
      IL-2R beta or the chimeric IL-2R alpha beta complex proliferate in response to IL
      2. Stably transfected cells expressing the chimeric high-affinity receptor (human
      IL-2R alpha and murine IL-2R beta) expressed de novo endogenous murine IL-2R
      alpha when cultured in the presence of IL-2 but not IL-4. Both chimeric and
      endogenous receptors are functional in response to IL-2, since only addition of
      both anti-human and anti-murine IL-2R alpha monoclonal antibodies (mAb) inhibited
      IL-2-induced proliferation. Taken together, our results strongly suggest that
      human and murine IL-2R beta molecules are different since interaction of IL-2
      with human p70 IL-2R is sufficient for transduction of proliferative signals in
      the absence of p55 IL-2R or, alternatively, that over-expression of the IL-2R
      beta chain renders cells responsive to IL-2. In addition, IL-2 stimulation of T
      cells through different forms of IL-2R results in the induction of distinct
      cellular responses.

PMID- 8262552
TI  - Interactions of promonocytic U937 cells with proteins of the extracellular
      matrix.
AB  - Monocyte interaction with proteins of the extracellular matrix (ECM) is regulated
      by expression of specific cell-surface receptors. 12-O-tetradecanoyl phorbol-13
      acetate (TPA) has been shown to induce the promonocytic cell line U937 to a more
      differentiated monocyte-like state. In this study we have analysed the attachment
      of U937 cells to ECM proteins and the effects of treatment with TPA on this
      process. Non-induced U937 cells attach to fibronectin- and Matrigel-coated
      surfaces without TPA stimulation, but TPA further increases adherence to these
      substrates as measured by an enhanced binding and by the lower concentration of
      proteins needed in the substrate to achieve 50% of maximal cell adhesion.
      Attachment to type I collagen was seen only with activated U937 cells, whereas no
      measurable attachment to bovine serum albumin, vitronectin, and type IV collagen
      was detected. TPA-activated U937 cells showed a two-fold increase in the
      expression of the RGD-dependent integrin receptors alpha 3 and alpha 5, and a
      reduction in the expression of alpha 4, another fibronectin-specific receptor,
      whereas the common beta 1 chain was unchanged. Attachment of U937 cells to
      fibronectin was primarily mediated by the alpha 3 and alpha 5 integrins, as
      revealed by the ability of GRGDS peptides to inhibit attachment, whereas the CS-1
      peptide, containing the alpha 4 binding site, was largely ineffective in blocking
      attachment.

PMID- 8262553
TI  - The contribution of a serum component(s) modified by B cells to the mechanism for
      macrophage activation by liposomes.
AB  - The effects of liposomes on the activation of mouse peritoneal macrophages were
      investigated in vitro by measuring the phagocytosis of opsonized sheep red blood
      cells (SRBC) via Fc receptors on the surface of macrophages. The addition of
      liposomes to mouse peritoneal exudate cells in RPMI-1640 medium with 10% fetal
      calf serum (FCS) caused an increase in the ingestion activity. In the absence of
      FCS, this increase was not observed, suggesting that some component(s) present in
      FCS is the causative factor(s) for this activation. When liposomes were added to
      the macrophage monolayer, the ingestion activity did not increase, showing that
      liposomes did not activate peritoneal macrophages directly, and that non-adherent
      cells may be involved. Following addition of the culture medium (conditioned
      medium), which was prepared by incubation of FCS with liposome-treated non
      adherent cells or cell ghosts, to the macrophage monolayer, the ingestion
      activity of macrophages increased in either case. When the conditioned medium
      prepared with liposome-treated B cells was used for cultivation of liposome
      untreated macrophages, a markedly enhanced ingestion activity was observed.
      However, the conditioned medium prepared with liposome-treated T cells did not
      affect the ingestion activity. These findings demonstrate that liposome-activated
      B cells modify some component(s) in FCS, and that the modified component(s)
      subsequently activates the phagocytosis of opsonized SRBC via Fc receptors on
      macrophages.

PMID- 8262555
TI  - CD69 is expressed by human eosinophils activated in vivo in asthma and in vitro
      by cytokines.
AB  - CD69 is an early activation marker for T cells and cross-linking of CD69 on
      platelets triggers aggregation and mediator release. Expression of a number of
      membrane receptors is induced on eosinophils after culture with certain
      cytokines. Therefore, we investigated whether cytokine-activated eosinophils
      expressed CD69. Unstimulated, peripheral blood eosinophils did not express CD69,
      as determined by immunofluorescence and flow cytometry (n = 15). CD69 expression
      was induced on eosinophils by granulocyte-macrophage colony-stimulating factor
      (GM-CSF) in a time- and dose-dependent manner. After 1 day in culture, expression
      was significant at concentrations of 10(-11) M and above. CD69 expression could
      be detected after stimulation with GM-CSF for only 1 hr, was significant after 2
      hr and was sustained over 1-2 days in culture. CD69 expression was also induced
      by interleukin-3 (IL-3), IL-5 and interferon-gamma (IFN-gamma), but stimulation
      of eosinophils with platelet-activating factor (PAF) (10(-6) M) for up to 2 hr
      did not induce CD69 expression. Cycloheximide (10(-6) M) significantly inhibited
      GM-CSF-induced CD69 expression, suggesting a requirement for protein synthesis.
      However, unlike up-regulation of CR3 expression, GM-CSF-induced CD69 expression
      was not inhibited by dexamethasone. CD69 was present on eosinophils from the
      bronchoalveolar lavage (BAL) fluid of patients with mild asthma (5/5), suggesting
      that the in vitro findings may have biological relevance in vivo. Therefore, CD69
      can be used as a marker of eosinophil activation by cytokines and is a candidate
      receptor for triggering eosinophil mediator release in the airways in asthma.

PMID- 8262554
TI  - Stimulation of murine peritoneal macrophage functions by neuropeptide Y and
      peptide YY. Involvement of protein kinase C.
AB  - The peptides neuropeptide Y (NPY) and peptide YY (PYY) at concentrations from 10(
      12) M to 10(-8) M have been shown in this study to stimulate significantly, in
      vitro, several functions of resting peritoneal macrophages from BALB/c mice:
      adherence to substrate, chemotaxis, ingestion of inert particles (latex beads)
      and foreign cells (Candida albicans), and production of superoxide anion measured
      by nitroblue tetrazolium reduction. A dose-response relationship was observed,
      with a maximal stimulation of the macrophage functions studied at 10(-10) M.
      These effects seem to be produced by specific receptors for the neuropeptides
      studied in peritoneal macrophages. Whereas the two peptides induced no change of
      intracellular cyclic AMP, they caused a significant stimulation of protein kinase
      C (PKC) in murine macrophages. These results suggest that NPY and PYY produce
      their effects on macrophage function through PKC activation.

PMID- 8262556
TI  - Cross-linking of monocyte plasma membrane Fc alpha, Fc gamma or mannose receptors
      induces TNF production.
AB  - We have studied and compared the effects of IgA and IgG immune complexes and
      concanavalin A (Con A) on human monocyte tumour necrosis factor (TNF) production.
      The presence of IgA-containing immune complexes in monocyte monolayers resulted
      in a dose-dependent increase of TNF production. Similar results were obtained
      with IgG-containing immune complexes and Con A. The presence of monomeric IgA or
      IgG did not increase TNF secretion. Both IgA and IgG immune complexes also
      increased monocyte interleukin-1 beta (IL-1 beta) production. Galactose inhibited
      the effect of IgA but not IgG immune complexes, while mannose inhibited the
      effect of Con A. Prednisolone abrogated TNF production, while indomethacin
      enhanced TNF production in all instances where cross-linking of plasma membrane
      receptors was achieved. These results indicate that activation of Fc alpha
      receptors (Fc alpha R), Fc gamma R or mannose receptors of the human monocyte
      plasma membrane by cross-linking results in increased TNF and IL-1 beta
      secretion. These findings may be of particular relevance in the pathogenesis of
      IgA immune complex-mediated disease.

PMID- 8262557
TI  - Differential effects of small tumour necrosis factor-alpha peptides on tumour
      cell cytotoxicity, neutrophil activation and endothelial cell procoagulant
      activity.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is a pluripotent cytokine with its
      receptors distributed throughout many different cell types. Because of the
      diverse effects of the cytokine, it is difficult to clearly define its role in
      infection and immunity, and appreciate its clinical therapeutic value. We have
      identified peptides derived from the primary amino acid sequence of human TNF
      alpha that have neutrophil-stimulating activity, as measured by enhanced
      chemiluminescence and superoxide production, and peptides which are both directly
      cytotoxic for tumour cells (WEHI-164) in vitro and also prevent TNF binding to
      tumour cells. However, only one of these neutrophil-stimulating peptides was
      toxic for tumour cells in vitro. Our results indicate that the region of amino
      acids 54-94 of human TNF-alpha has previously undescribed human neutrophil
      stimulatory activity, while peptides encompassing the regions 43-68 and 132-150,
      which are in close proximity, as indicated in the recently determined three
      dimensional structure of human TNF-alpha, have in vitro anti-tumour activity.
      These peptides also slowed tumour growth or induced tumour regression in WEHI-164
      tumour-bearing mice. The peptide 73-94, which activated neutrophils but which was
      not cytotoxic for tumour cells in vitro, also caused in vivo tumour regression,
      presumably by activating neutrophils with the consequent release of free radicals
      at the tumour site. Peptide 63-83, which was able to activate neutrophils in
      vitro, did not possess tumour regression activity in vivo. The TNF peptides
      described in this report did not elicit procoagulant activity in cultured bovine
      aortic endothelial cells and as such are devoid of at least one of the
      potentially lethal side-effects of elevated TNF levels in vivo.

PMID- 8262558
TI  - Membrane expression and shedding of tumour necrosis factor receptors during
      activation of human blood monocytes: regulation by desferrioxamine.
AB  - Previous studies have shown that desferrioxamine (DFX), an iron chelator
      preventing the synthesis of hydroxyl radical (OH.), up-regulates the cell-surface
      expression of tumour necrosis factor-alpha (TNF-alpha) receptors on unactivated
      human blood monocytes. In the present study, we investigated the regulatory
      action of DFX on 125I-TNF-alpha binding to monocytes upon exposure to bacterial
      lipopolysaccharide (LPS). Exposure to LPS (1 microgram/ml) resulted in almost
      complete loss of 125I-TNF-alpha binding to the surface of monocytes. This down
      regulation was reversible and the recovery observed after 18 hr was enhanced by
      addition of DFX (5 mM). However, binding studies on monocytes pre-exposed to low
      pH suggested that the DFX-induced increase of 125I-TNF-alpha binding was not due
      to differences in the number of receptors available but was probably due to a
      reduction of receptor occupancy by endogenously generated TNF-alpha. Time-course
      studies of TNF-alpha release from monocytes confirmed the ability of DFX to
      reduce the extracellular concentration of bioactive TNF-alpha through a decrease
      of its synthesis and an increase of its inactivation. The latter process was
      associated with an increased expression of the soluble form of TNF-alpha receptor
      type II. These results indicate that, in the presence of LPS, DFX increases the
      release of soluble TNF-alpha receptors from monocytes. Thus, conversely, OH.
      generated in situ could reduce the shedding of soluble TNF-alpha receptors and,
      hence, increase the widespread release of bioactive TNF-alpha.

PMID- 8262559
TI  - Influence of the antigen delivery system on immunoglobulin isotype selection and
      cytokine production in response to influenza A nucleoprotein.
AB  - The influence of different antigen delivery systems on antibody isotype and
      lymphokine profile has been investigated using influenza nucleoprotein as a model
      antigen system. Mice exposed to live or inactivated influenza virus produced
      antibody against whole virus or recombinant nucleoprotein (rNP), which was
      predominantly of the IgG2a isotype. Spleen or lymph node cells from these mice
      rapidly produced large amounts of interferon-gamma (IFN-gamma), but no detectable
      interleukin-5 (IL-5) when stimulated in vitro with specific antigen. In contrast,
      after primary immunization with rNP or p206-229 in different adjuvants (CFA, quil
      A or alhydrogel), specific antibody was predominantly of the IgG1 isotype and
      relatively lower amounts of IFN-gamma but no IL-5 were detected following in
      vitro antigenic stimulation. Secondary immunization, however, resulted in
      detection of IgG2a antibodies and increased levels of IFN-gamma. IL-5 was only
      detected after secondary immunization with peptide in adjuvant. Mice infected
      with aro A- Salmonella typhimurium expressing NP produced antibody of both IgG1
      and IgG2a isotypes and large amounts of IFN-gamma and no IL-5, following in vitro
      antigenic stimulation, and therefore parallelled the pattern seen with whole
      virus more closely than that seen following primary immunization with protein or
      peptide in conventional adjuvants. The results suggest that the antigen delivery
      vehicle influences both quantitative and qualitative differences in the type of
      immune response elicited, which may be important in determining the potency of
      protective immunity induced.

PMID- 8262560
TI  - Relative immunogenicity of hepatitis B virus-encoded antigens as targets for
      cytotoxic T-cell response.
AB  - To analyse the immunological mechanism of hepatocellular injury in hepatitis B
      virus (HBV) infection, the immunoreactivity of HBV-encoded antigens as a target
      for cytotoxic T lymphocyte (CTL) response was examined using recombinant vaccinia
      virus (RVV) expressing surface protein (S), precore/core protein (PC), and core
      protein (C) of HBV. C3H/He mice (H-2k) were inoculated with each RVV. Their
      spleen cells were then harvested and stimulated in vitro with the histocompatible
      transfectant, which stably expressed hepatitis B surface antigen (HBsAg),
      hepatitis B e antigen (HBeAg), and hepatitis B core antigen (HBcAg), and used as
      effectors. As the targets, L cells (H-2k) infected with individual RVV were used.
      Cytotoxic test was performed with various combinations and ratios of effectors
      and targets. The reactivity of PC-primed effectors against PC-expressing targets
      was greatest with 71.4% specific lysis on average at an effector/target ratio of
      12.5:1 among all the combinations. C-primed effectors against C-expressing target
      also revealed rather high cytotoxicity (specific lysis, 40.6% at an E/T ratio of
      12.5:1). Furthermore, PC-primed and C-primed effectors showed a cross-reactivity
      to the targets expressing other nucleocapsid antigen, respectively. S-primed
      effectors showed less lytic activity against S-expressing targets (specific
      lysis, 18.4% at an E/T ratio of 12.5:1). The CTL responses were blocked by anti
      CD8 and anti-major histocompatibility complex (MHC) class I antibodies, but not
      by anti-CD4 or anti-MHC class II. These findings suggest that endogenously
      synthesized nucleocapsid antigen, especially PC, is a dominant target for the MHC
      class I-restricted CTL in H-2k mice and that this system may work as an efficient
      model to study immunopathogenesis of HBV infection.

PMID- 8262561
TI  - High expression of NK-1.1 antigen is induced by infection with murine AIDS virus.
AB  - Spleen cells from mice infected with LP-BM5 MuLV, a causative agent of murine
      acquired immunodeficiency syndrome (MAIDS), were tested for frequency of NK-1.1+
      cells and natural killer (NK) activity. During the first 3 weeks following
      infection, NK activity was well conserved, but by 9-12 weeks post-infection
      (p.i.), killer activity was depressed; however, the frequency of NK-1.1+ cells
      increased within 4 weeks of infection and remained elevated thereafter, even
      following the decline in functional killing activity. Since the absolute number
      of NK-1.1+ cells increased after infection, the ability of each NK-1.1+ cell to
      kill the targets seems drastically impaired. Extraordinary expansion of NK-1.1
      positive cells was induced by infection with LP-BM5-defective virus (BM5def), a
      crucial element for MAIDS induction, but not with a helper non-pathogenic virus.
      With advance of MAIDS the NK-1.1 antigen (Ag) was preferentially expressed on
      B220+ and Thy-1+ cells, in contrast to CD4+ and CD8+ cells, and among activated
      large cells a higher proportion was NK-1.1+ than NK-1.1-. Mice with graft-versus
      host disease (GVHD) due to class II major histocompatibility complex (MHC) Ag
      disparity showed a high frequency of NK-1.1 expression in association with other
      phenotypic alterations, very similar to those seen in mice with MAIDS. In
      contrast, B6-lpr/lpr mice developed similar activation of B cells but did not
      exhibit enhanced expression of the NK-1.1 marker. Thus, enhanced expression of
      the NK-1.1 Ag might be associated with chronic activation of lymphocytes through
      a common but not universal pathway.

PMID- 8262562
TI  - Elimination of IgE regulatory rat CD8+ T cells in vivo increases the co-ordinate
      expression of Th2 cytokines IL-4, IL-5 and IL-10.
AB  - Immunization of rats with soluble antigen (ovalbumin) and the castor bean toxin,
      ricin, eliminates a subpopulation of CD8+ T cells which suppress IgE responses in
      vivo. This treatment also reduces the ability of splenic T cells to produce
      interferon-gamma (IFN-gamma) and enhances their capacity to make interleukin-4
      (IL-4). In this report we describe the effect of immunization with ricin and
      antigen on the expression of mRNA for other T-helper type 2 (Th2) cytokines--IL-5
      and IL-10--and their relationship to serum IgE and IL-4 mRNA expression.
      Splenocytes were taken from rats at different times after immunization with
      antigen or ricin and antigen and activated in vitro with phorbol myristate
      acetate (PMA) and ionomycin for 6 hr and total RNA extracted and reverse
      transcribed. Cytokine gene expression was detected using a quantitative
      polymerase chain reaction (PCR). Expression of IL-4, IL-5, and IL-10 was
      increased 7-20-fold 11 days after immunization with ricin and antigen (from
      0.107% to 0.769% beta-actin for IL-4, from 0.0167% to 0.381% beta-actin for IL-5,
      and from 0.0581% to 0.954% beta-actin for IL-10), and preceded maximum serum IgE
      levels by 4-5 days. There was no increase in IgE or mRNA for these cytokines in
      rats immunized with antigen alone. The level of IL-4, IL-5, and IL-10 expression
      declined rapidly after 12 days. Our results suggest that immunization with
      antigen and ricin preferentially induces a Th2 response, and that CD8+ T cells
      may play a part in down-regulating the development of Th2 T cells.

PMID- 8262563
TI  - Augmented production of interleukin-8 in cerebrospinal fluid in bacterial
      meningitis.
AB  - Interleukin-8 (IL-8) elaborated by monocytes and endothelial cells is a cytokine
      which is responsible for adhesion of leucocytes to vascular endothelium and
      migration of neutrophils into the cerebrospinal fluid (CSF) from the
      intravascular space. The inflammation in meningitis is elicited by the cytokine
      release from leucocytes which encounter micro-organisms in the arachnoid or
      subarachnoid space. In bacterial meningitis, tumour necrosis factor (TNF), IL-1
      and IL-6 are produced vigorously, and initiate and augment the inflammation in
      the central nervous system. In this study, utilizing a quantitative immunometric
      sandwich enzyme immunoassay, the concentration of IL-8 was investigated in the
      CSF of patients with bacterial meningitis, patients with aseptic meningitis, and
      patients with gastroenteritis who served as controls. The IL-8 concentration was
      markedly higher in the CSF of patients with bacterial meningitis (224 +/- 2.57
      pg/ml; mean +/- SD) than in the CSF of patients with aseptic meningitis (less
      than 30 pg/ml). The IL-8 level in the CSF of patients with aseptic meningitis did
      not differ from that in the CSF of the patients with gastroenteritis (less than
      30 pg/ml). The augmented production of IL-8 in CSF may account for the
      inflammation in bacterial meningitis being more severe than that in aseptic
      meningitis.

PMID- 8262564
TI  - A rapid microplate-based fluorometric assay for phagocytosis.
AB  - A highly sensitive quantitative fluorometric assay for phagocytosis, previously
      measured using fluorescence spectrophotometry or flow cytometry, has been adapted
      for use with a 96-well fluorescence plate reader. The technique allows rapid
      analysis of large numbers of samples, and requires only a small sample volume.
      Comparison of plate types demonstrated that opaque white 96-well luminostrips
      produced a 100 fold greater fluorescent output, and were more sensitive than
      black fluoroplates. Intraplate variability was also significantly lower using
      white luminostrips. For the phagocytic assay, fluorescein conjugated polystyrene
      beads were incubated with macrophage monolayers in white luminostrips. After
      incubation, cells were washed, lysed and phagocytosis quantified by determining
      the fluorescent intensity using a fluorescence plate reader. The number of beads
      phagocytized was determined from a standard curve of bead number versus
      fluorescent output. The phagocytic activity of resident and thioglycollate
      elicited peritoneal macrophages was compared using this technique.

PMID- 8262565
TI  - Calcium uptake during mitogenic stimulation of human lymphocytes:
      characterization of intracellular calcium compartments and demonstration of the
      presence of immunoreactive calrecticulin.
AB  - Phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes (HPBL)
      rapidly increases 45Ca2+ uptake into intracellular pools. Detectable increase in
      45Ca2+ uptake occurred only on exposure to mitogenic lectins but not with non
      mitogenic lectins. However, intracellular free Ca2+ concentration [(Ca2+)i]
      increased comparably on exposure to either mitogenic or non-mitogenic lectins.
      Permeabilization of 45Ca2+ loaded cells revealed distinct pools of Ca2+ uptake.
      The highly digitonin sensitive pool #I (permeabilized by 0.02% digitonin)
      exchanged slowly and included a part that represented endoplasmic reticulum. Pool
      II was defined by lower digitonin sensitivity, had a much faster initial uptake.
      Pool III was digitonin-resistant and predominantly non-vesicular. During the
      first 120 min of PHA stimulation, significant increase in 45Ca2+ uptake occurred
      only into pool II. Progressive increase in uptake into pool I then occurred so
      that by 24 hours, this pool constituted the major fraction of PHA induced
      increment in total 45Ca2+ uptake. Using specific antibody to the calcium binding
      protein calreticulin, an analogous immunoreactive protein was detectable in
      resting HPBL. PHA stimulation led to a striking increase in abundance of
      immunoreactive calreticulin so that 24 hrs after PHA stimulation, there was a 28
      and 3.4 fold increase in the amount of immunoreactive calreticulin present in the
      non-particulate fraction and the total particulate membrane fraction,
      respectively. A major part (72%) of the total cellular immunoreactive
      calreticulin in PHA stimulated cells at 24 hrs was released into the medium after
      permeabilization of lymphocytes with 0.02% digitonin, corresponding to the
      location of calcium uptake pool I.

PMID- 8262566
TI  - Tumoricidal activity of mouse peritoneal macrophages treated with Viscum album
      extract.
AB  - Macrophages from mice treated with Viscum album extract were shown to be active
      in inhibiting the proliferation of tumour cells in culture. These activated
      macrophages have now been shown to protect mice from dying of progressive tumours
      when injected intraperitoneally into the animals. Prophylactic as well as
      multiple treatments with macrophages activated with Viscum album extract seemed
      more effective than a single treatment. The present finding suggests that in
      addition to a direct cytotoxic effect of Viscum album extract, the activation of
      macrophages may contribute to the overall antitumor activity of the drug.

PMID- 8262567
TI  - Specific ELISAs for the detection of human macrophage inflammatory protein-1
      alpha and beta.
AB  - Mononuclear cell elicitation has gained renewed interest with the discovery of a
      supergene family of small polypeptide chemotactic cytokines (< 10 kD). These
      chemotactic cytokines have been divided into the C-X-C and C-C chemokine families
      depending upon whether the first two conserved cysteine amino acid residues are
      separated by one amino acid or are in juxtaposition, respectively. A salient
      feature of the C-C chemokine family is their ability to induce both monocyte and
      lymphocyte chemotaxis. Although monocyte and lymphocyte migration in vitro is
      measured in chemotactic bioassays, this technique often fails to determine the
      specific quantitative contribution of a chemotaxin to a biological specimen. Our
      laboratory has developed two sensitive and specific sandwich ELISAs for the
      detection of macrophage inflammatory protein-1 alpha and beta (MIP-1 alpha and
      MIP-1 beta). The lower threshold for detection of both MIP-1 alpha and MIP-1 beta
      was 100 pg/ml, and both of these ELISAs were efficacious for the detection of MIP
      1 alpha and MIP-1 beta in conditioned media from pulmonary fibroblasts,
      monocytes, neutrophils, and a pulmonary epithelial cell line. The development of
      these ELISAs will allow the measurement of MIP-1 alpha and MIP-1 beta from
      biologically relevant fluids and ascertain whether these two C-C chemokines are
      present in disease.

PMID- 8262569
TI  - Plasmid profile analysis of Salmonella ser. Typhimurium phage untypable strains
      encountered in diverse geographic regions of India.
AB  - Plasmid profile analysis and antibiotic resistance pattern determination were
      carried out for 117 phage untypable S. Typhimurium strains. Majority of the
      strains (82%) were resistant to all the seven antibiotics tested, R-pattern being
      ApCmKmSmSuTcTp, rest (12%) showed heterogenous R-patterns. Plasmid DNA analysis
      revealed phage untypable strains to harbour large (58.8-114.3 MDal), intermediate
      size (36 MDal, 42 MDal) and small (1.8-5.2 MDal) plasmids with varying molecular
      weights. All the phage untypable strains could be subgrouped by plasmid profile
      analysis into 23 plasmid patterns. Plasmid profile analysis could discriminate
      large number of phage untypable strains on the basis of their plasmid pattern.

PMID- 8262568
TI  - Tumor growth alters macrophage responsiveness to macrophage colony-stimulating
      factor during reactivity against allogeneic and syngeneic MHC class II molecules.
AB  - Tumor-induced changes in macrophage (M phi)2 accessory activities significantly
      suppress T-cell recognition of allogeneic and syngeneic major histocompatibility
      complex (MHC) class II molecules. Because these changes are often associated with
      altered responses to stimulatory and inhibitory cytokines, we investigated the
      possibility that tumor growth alters the contribution of a macrophage regulatory
      cytokine, macrophage colony-stimulating factor (M-CSF), during reactivity against
      allogeneic and syngeneic MHC class II molecules. T-cell reactivity against
      allogeneic MHC class II molecules was significantly suppressed by tumor-bearing
      host (TBH) M phi in the presence of M-CSF. M-CSF-induced suppression was
      independent of TBH M phi prostaglandin E2 (PGE2) synthesis. T-cell reactivity
      against syngeneic MHC class II molecules increased in the presence of M-CSF when
      normal host (NH) M phi served as the source of syngeneic molecules. However, T
      cell reactivity against syngeneic MHC class II molecules in the presence of M-CSF
      did not change when TBH M phi served as stimulator/accessory cells. Although T
      cell reactivity against NH syngeneic MHC class II molecules was additively
      increased by M-CSF and indomethacin (a PGE2 synthesis inhibitor) treatment,
      reactivity against TBH syngeneic MHC class II molecules increased solely through
      PGE2 synthesis inhibition. Admixtures of both NH and TBH M phi in the absence or
      presence of M-CSF suggest that tumor-induced suppression was not strictly due to
      decreased expression of MHC class II molecules. Collectively, these data suggest
      that TBH M phi are partly suppressive through altered responsiveness to M-CSF.

PMID- 8262570
TI  - Plasmid profiles, adhesive & invasive properties of Salmonella ser. Typhimurium
      strains: phage types 99 & 36.
AB  - Adhesive and invasive properties were compared with plasmid profile in S.
      Typhimurium strains of phage type 99(10) and 36(10). All strains of phage type 99
      were multiple drug resistant (ApCmKmSmSuTcTp) and harboured small plasmids of 2.4
      5.2 MDal. Six strains of the phage type 36 had ApCmTc R-pattern and two with only
      ampicillin resistance, carried plasmids of molecular size 2.6-5.2 MDal; two
      strains were sensitive to all antibiotics and devoid of plasmids. None of the
      strains were found to harbour high molecular weight plasmids. All plasmid
      positive strains of phage types 99 and 36 could be divided into two groups of
      three plasmid patterns each, which were phage type specific. All plasmid positive
      and negative strains adhered and invaded HeLa cells to different degrees. No
      correlation could be established between plasmid profile and adhesion invasion
      characteristics. High molecular weight plasmids therefore are unlikely to be
      essential for adhesion and invasion.

PMID- 8262571
TI  - An outbreak of Serratia marcescens infection among obstetric patients.
AB  - An outbreak of S. marcescens infection occurred among 17 obstetric patients
      during May-June 1990. Simultaneously 11 newborns were also affected. All the 28
      strains were identical in their biochemical characteristics, serotype and phage
      type as well as antimicrobial susceptibility pattern. The source of infection was
      traced to a contaminated batch of cream, consisting of 0.5 per cent savlon in
      carboxy methyl cellulose base, used while doing pelvic examination. The affected
      patients were treated with appropriate antibiotics and there was no mortality. No
      further infection was reported after the removal of the contaminated cream.

PMID- 8262572
TI  - Studies on antibacterial properties of gentian violet impregnated silastic.
AB  - The antibacterial activity of gentian violet (GV) impregnated silastic discs was
      studied by measuring the zone of inhibition (ZOI), (in mm) produced by the discs
      planted on Staphylococcus epidermidis seeded agar plates. The effect of varying
      concentration of GV, the duration of antibacterial activity and effect of
      autoclaving were studied. The mean ZOI for 1 per cent GV was 19.28 +/- 0.89 mm
      and for 2 per cent GV it was 22.55 +/- 0.71 mm (P < 0.001). There was no
      significant difference between GV concentrations of 2-5 per cent. Over a period
      of 1-5 wk, no significant difference was found in the antibacterial activity of
      GV for any of the concentrations. In each of the concentrations there was a
      significant reduction in the ZOI after multiple autoclavings. The study thus
      indicates that it is possible to impart antibacterial properties to silastic
      implants so that their colonization with Staph. epidermidis can be prevented and
      this finding has obvious clinical implications.

PMID- 8262573
TI  - Histological changes in hamster liver by ES antigen of Ascaris suum.
AB  - Polyacrylamide gel electrophoresis with SDS (PAGE-SDS) of the ES antigens of A.
      suum revealed several protein molecules which differed from those obtained in ES
      antigens of A. lumbricoides. Nature of liver damage caused by ES antigens of A.
      suum was studied in hamsters to find out the nature of damage and to compare with
      those caused by ES antigens of A. lumbricoides. Feeding of ES antigens of A. suum
      was carried out in 7 hamsters for 75 days. After such feeding gross hepatic
      damage was noticed. This was characterized by pericentrivenular degeneration and
      necrosis of liver parenchyma, the lesions being different and much more severe
      than those observed in hamster challenged by ES products of A. lumbricoides. The
      lesions appear to be immune mediated.

PMID- 8262574
TI  - Vapour toxicity of aerosol formulation, allethrin on Culex quinquefasciatus
      (Diptera: Culicidae), Say & Musca domestica (Diptera: Muscidae) N.
AB  - Studies on the toxicity of aerosol vaporizer formulation, allethrin were carried
      out on both male and female species of C. quinquefasciatus and M. domestica at
      different times of exposure. ANOVA models revealed significant differences in the
      mean values of the percentage mortalities in relation to sex and time-of-exposure
      for both the species.

PMID- 8262575
TI  - Comparative susceptibility of two Japanese encephalitis vectors from Mysore to
      six insecticides.
AB  - Larval populations of Culex tritaeniorhynchus and C. fuscocephala from Mysore
      city were tested for their susceptibility against two pyrethroids viz.,
      cypermethrin and deltamethrin and four organophosphorus (OP) compounds viz.,
      fenthion, fenitrothion, temephos and malathion. The investigations revealed that,
      among the pesticides tested, efficacy of pyrethroids was very high as compared to
      OP compounds. C. tritaeniorhynchus was found to be highly tolerant to all the
      insecticides used. It registered 4.0, 6.5, 17.0, 6.5, 14.0 and 1.5 times more
      tolerance than C. fuscocephala to cypermethrin, deltamethrin, fenthion,
      fenitrothion, temephos and malathion respectively in terms of the LC50 value.
      Further studies are needed to determine the development of resistance if any, by
      C. tritaeniorhynchus, an important JE vector in Karnataka.

PMID- 8262576
TI  - Role of enteral hyperalimentation in patients of carcinoma oesophagus.
AB  - The nutritional status of 24 patients of carcinoma oesophagus was assessed before
      and after central hyperalimentation with a liquid blenderized diet containing
      3000-3500 cal and 100-120 g protein. The overall prevalence of malnutrition was
      found to be 70.8 per cent before the initiation of therapy. Of the various
      parameters used for assessment of nutritional status weight loss was the most
      common finding (91.6%) followed by alteration in midarm circumference,
      haemoglobin, triceps skin fold thickness, midarm muscle circumference and serum
      albumin. Enteral hyperalimentation for 10 days improved nutritional status by
      inducing significant gain in body weight (74.1%), triceps skin fold thickness
      (50%), midarm circumference (58%), midarm muscle circumference (62.5%) and serum
      albumin levels (91.6%). There was no significant change in haemoglobin levels.

PMID- 8262577
TI  - Loading dose diazepam therapy for alcohol withdrawal state.
AB  - Two dose regimens of diazepam, conventional dose and loading dose, were randomly
      given for the treatment of alcohol withdrawal state in 21 and 20 male subjects,
      respectively. Total dose of diazepam in conventional and loading dose groups were
      200 mg and 67 +/- 9.3 mg, respectively. Clinical response was comparable in both
      the groups. None of the subjects developed diazepam related side effects.

PMID- 8262578
TI  - Midazolam as an induction agent in mitral stenosis patients for closed mitral
      commissurotomy.
AB  - In 30 patients of rheumatic heart disease with mitral stenosis (MS) belonging to
      NYHA class II and III scheduled for closed mitral commissurotomy anaesthesia was
      induced with morphine 0.15 mg/kg followed by either thiopentone (group A, n = 15)
      or midazolam (group B, n = 15) titrated to produce sleep. Patients were intubated
      with pancuronium bromide in a dose of 0.12 mg/kg. Minimum mean arterial blood
      pressure following induction was significantly lower in thiopentone group (77 +/-
      7 mm Hg) than midazolam group (85 +/- 6 mm Hg; P < 0.05). After intubation blood
      pressure was significantly higher in thiopentone group (99 +/- 8 mm Hg) than
      midazolam group patients (89 +/- 7 mm Hg). Heart rate was significantly higher in
      thiopentone treated patients both before and after endotracheal intubation.
      During surgery, three patients in group A had hypotensive episodes (mean arterial
      blood pressure 20% below basal at two successive readings 5 min apart) while one
      in group B had a hypotensive episode. Average duration of surgery was comparable
      between the two groups (102 +/- 15 and 95 +/- 18 min) and postoperatively there
      was no significant difference in sedation score and incidence of nausea and
      vomiting between the two groups.

PMID- 8262579
TI  - Experimental studies on the treatment of frostbite in rats.
AB  - The effect of treatment by high dose of vitamin C, rapid rewarming by 37 degrees
      C water alone and with vitamin C, rapid rewarming by 37 degrees C decoction of
      Indian black tea alone and with vitamin C for experimentally produced frostbite
      was evaluated in 6 groups (25 each) of rats. Frostbite was produced
      experimentally in the hind limbs by exposing the animals at -15 degrees C for 1h
      using the harness technique. The degree of injury was assessed and classified on
      the basis of tissue necrosis at the end of 15 days. Administration of high dose
      of vitamin C for prolonged period and rapid rewarming at 37 degrees C water bath
      immediately after cold exposure apparently reduced the tissue damage. High dose
      of vitamin C therapy preceded by rapid rewarming in plain water showed additional
      benefit. Rapid rewarming in decoction of Indian tea resulted in identical
      beneficial effect. The degree of tissue preservation was highest with rapid
      rewarming in tea decoction followed by high dose of vitamin C.

PMID- 8262580
TI  - Effect of some steroidal & non-steroidal anti-inflammatory drugs on purified goat
      brain cathepsin L.
AB  - The lysosomal cysteine proteinases have been found to be involved in various
      inflammatory conditions. Inhibitory effects of certain commonly used anti
      inflammatory drugs were observed on lysosomal thiol proteinase cathepsin L. Of
      the non-steroidal anti-inflammatory drugs tested, phenylbutazone was found to be
      most potent inhibitor of cathepsin L activity. The half maximal inhibition was
      achieved at 0.6 mM concentration. The inhibition by phenylbutazone was of non
      competitive type, with a ki of 1.3 x 10(-3) M. Flufenamic acid and indomethacin
      were also inhibitory to cathepsin L activity, giving half maximal inhibitions at
      3.5 mM and 4.5 mM concentrations respectively. In contrast, cathepsin L activity
      was not affected at all by steroidal anti-inflammatory agents. Aspirin was also
      found to have no effect on cathepsin L activity whereas salicylic acid, its m-
      and p-analogs exhibited inhibitory effects but to a lesser degree.

PMID- 8262581
TI  - Effect of toxaphene toxicity on enzyme activity & residue levels in vital organs
      of guineapig.
AB  - Guineapigs exposed to acute and subacute levels of toxaphene revealed a marginal
      reduction in the body weight. There was a significant inhibition of
      acetylcholinesterase and ATPases in the brain, liver and kidney. The effect of
      subacute toxicity of toxaphene resulted in an enhancement of cytochrome P450 and
      induction of aniline hydroxylase in liver and kidney. Biochemical investigations
      on the backbone revealed that toxaphene toxicity caused an increase in the
      calcium content and a decrease in the collagen content significantly. Toxaphene
      was accumulated more in the liver than in the kidney as reflected by residue
      studies.

PMID- 8262582
TI  - Detection & elimination of preanalytical errors in the determination of zinc in
      biological samples.
AB  - Exogenous contamination poses a major problem to accurate determination of trace
      metals in biological samples. Analysis of these elements in biological material
      entails adoption of special precautionary measures. In this study we have
      assessed the various procedural steps of sampling and analysis of zinc in order
      to identify and minimize extraneous contamination in the laboratory. In addition
      we have established reference limits (2 SD) for zinc in human plasma,
      erythrocytes and hair.

PMID- 8262583
TI  - Application of silver colloidal staining method in the diagnosis of intracranial
      glioma.
AB  - A silver colloidal staining technique for the demonstration of argyrophilic
      nucleolar organizer regions (Ag-NORs) was used on the paraffin sections of
      reactive gliosis and grade I astrocytoma tissue. Quantitative as well as
      qualitative differences of Ag-NORs were found between the cells of reactive
      gliosis and grade I astrocytoma. In cases of reactive gliosis, the Ag-NOR counts
      averaged 1.19 +/- 0.16 per nucleus, while in grade I astrocytoma, Ag-NOR counts
      averaged 2.36 +/- 0.32 per nucleus (P < 0.05). Compound Ag-NORs were also seen in
      the nuclei of cells in grade I astrocytoma while they were not present in the
      nuclei of cells in cases of reactive gliosis. The results of the study indicate
      that Ag-NOR technique is an useful method and can be applied in situations where
      a distinction between grade I astrocytoma and reactive gliosis becomes difficult
      at the light microscopic level.

PMID- 8262584
TI  - Identification of infertile couples in a rural area of northern India.
AB  - An attempt was made to identify infertile couples in a rural area of India,
      utilizing the existing information structure. A three stage screening of the
      cases was done. Initial record based listing was done with the help of the health
      workers' records. Cases on initial list were screened on the basis of information
      obtained from key informants in villages. Verified cases were then individually
      contracted. Total catchment population (28839) in 40 villages of a Primary Health
      Centre (PHC) of north India was surveyed by a lady social worker. Of the total
      4453 eligible couples in the PHC, 129 (2.9%) were infertile (46.5% primary and
      53.5% secondary infertility). From the initial list of 298 cases, 161 (54%) were
      excluded during the survey. The yield from the health workers' record was 33 per
      cent whereas from key informants it was 93 per cent. The study revealed that the
      key informants and existing information structure can be utilized to identify
      conditions like infertility in rural areas, after proper verification of initial
      reports.

PMID- 8262585
TI  - What constitutes a "safe" level of bilirubin concentration in preterm and full
      term infants?

PMID- 8262586
TI  - Present status and future prospects of oral iron chelation therapy in
      thalassaemia and other diseases.
AB  - In the last few years we have witnessed the emergence of oral chelation which is
      a new form of therapy for transfusional iron-loaded patients in thalassaemia and
      other refractory anaemias. The need for a cheap, non-toxic, orally effective iron
      chelator is paramount because it could potentially save the lives of many
      thousands of patients. At present, less than 10% of the patients requiring iron
      chelation therapy worldwide receive the widely used chelating drug
      desferrioxamine (DF) because of its high cost, oral inactivity and toxicity. The
      most promising oral iron chelator is 1, 2-dimethyl-3-hydroxypyrid-4-one (L1 or
      INN: Deferiprone), which has so far been taken by over 450 patients in 15
      countries, and in some cases daily for over 4 years with very promising results.
      L1 was shown at 50-100 mg/kg/day to be effective in bringing patients to negative
      iron balance. It increases urinary iron excretion, decreases serum ferritin
      levels and reduces liver iron in multi-transfused iron-loaded patients. Toxic
      side effects were mainly encountered at high doses (80-100 mg/kg/day) and include
      transient agranulocytosis (5 cases), transient musculoskeletal and joint pains
      (10-20%), gastric intolerance (2-6%) and zinc deficiency (1%). The incidence of
      these toxic side effects was reduced by using lower doses of 50-75 mg/kg/day. The
      overall efficacy and toxicity of L1 is comparable to that of DF in animals and
      humans. Further work is required for identifying susceptible individuals to L1
      toxicity, and also optimum dose protocols of L1 which can maximise iron excretion
      and minimise the incidence of toxic side effects.

PMID- 8262587
TI  - Oral iron chelation: a review with special emphasis on Indian work on deferiprone
      (L1).

PMID- 8262588
TI  - Bone marrow transplantation for thalassemia.
AB  - Early trials of allogeneic bone marrow transplantation (BMT) for homozygous beta
      thalassemia and the analyses of results of transplantation in patients less than
      16 years old have allowed us to identify three classes of risk using the criteria
      of degree of hepatomegaly, the degree of portal fibrosis and the quality of the
      chelation treatment given before the transplant. Patients for whom all three
      criteria were adverse constituted class 3, patients with none of the adverse
      criteria constituted class one and patients with one or various association of
      the adverse criteria formed Class 2. Most patients older than 16 years have
      disease characteristics that place them in class 3 with very few in class 2. For
      all the patients with an HLA identical donor we are actually using two Protocols
      for BMT to whom the patients are assigned on the base of the class they belong to
      at the time of BMT and independently on the age of the patient. For class 1,
      class 2 and for class 3 the probabilities of survival and of event-free-survival
      are respectively of 98% and 94%, 87% and 84%, 100% and 67%. For those patients
      that were older than 16 years at the time of the transplant, the probabilities of
      survival are 82% and the probabilities of event-free survival are 79%. Bone
      marrow transplantation is a new form of radical treatment of thalassemia in those
      patients with an HLA identical donor.

PMID- 8262589
TI  - An odyssey in search of a cure: the evolution of treatment of childhood acute
      lymphoblastic leukemia in the United Kingdom.
AB  - This review charts the evolution of therapy for childhood acute lymphoblastic
      leukaemia (ALL) in the United Kingdom. The present chemotherapeutic regimen is
      the result of experience gained from carefully planned randomised cooperative
      studies carried out during the last two decades. In common with the experience of
      the West German and American groups, the best results have been in those treated
      with post remission intensification blocks. With current chemotherapy protocols,
      almost 70% of children with ALL in U.K. can be cured but there may be a medical
      cost of such a cure, in terms of both acute and long term toxicity. This was
      especially true when central nervous system (CNS) therapy with cranial
      irradiation was used. Therefore present regimens are examining chemotherapeutic
      options for CNS disease control and the efficacy of additional post remission
      intensification. Failure of chemotherapy is most often seen in those children
      with a presenting white cell count of more than 50 x 10(9)/l, very young children
      and/or the presence of certain chromosomal rearrangements (e.g. t4: 11, t9: 22).
      At present the optimum therapeutic option for such high risk patients and for the
      majority of those in second remission, is an allogenic bone marrow transplant if
      an HLA-matched sibling is available. Modern day therapy is both complicated and
      costly and will be beyond the resources available for most children with ALL in
      developing countries. A significant decrease in worldwide mortality due to ALL
      will only occur if either the disease can be prevented or a simpler cure devised.

PMID- 8262590
TI  - Bone marrow transplantation.
AB  - Bone marrow transplantations have a definite role in treatment of leukemias and
      lymphomas. In acute myeloid leukemia and CML an allogeneic transplant using an
      HLA identical donor certainly provides a far superior survival than chemotherapy.
      Patients with Ph' chromosome need to be transplanted in first remission if a
      suitable donor is available. In recurrent lymphomas the best results are achieved
      if the patient is transplanted in complete remission. Transplantation done using
      minor mismatched family donors or unrelated donors are still considered
      experimental and more data is needed before final recommendations can be made.
      Availability of supportive services is an absolute must prior to establishing
      transplant program. Selection of patients for transplantation should be done
      after carefully reviewing the indications and discussing with the family the
      emotional, financial and physical burden of the procedure. For selected
      indications in leukemias and lymphomas, BMT may be the only viable treatment
      option and therefore must be considered.

PMID- 8262591
TI  - Current treatment and prognosis of Wilms' tumor.
AB  - Thanks to the nationally and internationally organized efforts refinements in the
      therapy of Wilms' tumor have allowed restructuring and reduction of therapeutic
      strategies. A decrease in tumor relapse and long term sequelae are the immediate
      goals which will no doubt be the result of tailoring chemotherapy and radiation
      therapy exposure together with improved surgical techniques and outstanding
      supportive care.

PMID- 8262592
TI  - Evaluation of sepsis screen for diagnosis of neonatal septicemia.
AB  - Fifty clinically suspected cases of neonatal septicemia were studied for
      evaluating the role of sepsis screen. Sensitivity and specificity of C-reactive
      protein test, micro-ESR, gastric aspirate cytology for polymorphs and toxic
      granules in neutrophils were studied singly and in combinations of two and three
      tests. Positive blood culture was obtained in only 20% cases, thereby underlying
      the need for a sepsis screen in the diagnosis of neonatal septicemia, especially
      in areas where adequate micro-biological facilities are lacking.

PMID- 8262593
TI  - Clinical profile of klebsiella septicemia in neonates.
AB  - A detailed clinical study of 51 consecutive cases of neonatal klebsiella
      septicemia was carried out prospectively over a 20 months period. The incidence
      was 6.27 per 1000 live births. Majority (85.5%) were either preterms or small for
      date. Almost fifty percent babies had associated perinatal risk factors. Mean age
      of onset was 5.7 +/- 2.2 days. General symptoms were the earliest to occur at
      mean age of 5.7 days followed by respiratory, alimentary, hematological and
      neurological symptoms at 6.2, 6.3, 6.6 and 7.9 days respectively. About half of
      the neonates had associated complications; commoner being meningitis (20%),
      bleeding manifestations and sclerema (17.6% each) and pneumonia (15.7%).
      Cefatoxime was found to be the drug of choice (86% sensitivity). Nine babies
      (17.6%) died during the study period at a mean age of 9.1 +/- 3.2 days. Mean
      duration of hospital stay in rest of neonates was 27.9 +/- 12.1 days.
      Neurological symptoms were commoner in late onset disease. Bleeding
      manifestations, sclerema and granulocytopenia were seen exclusively in preterms.
      Presence of respiratory symptoms, bleeding, sclerema, shock and granulocytopenia
      were identified as poor prognostic factors in neonatal klebsiella septicemia.

PMID- 8262594
TI  - Clinico-hematological profile and natural history of childhood myelodysplastic
      syndromes.
AB  - The clinical and hematological characteristics of ten children with
      myelodysplastic syndromes diagnosed and followed up over a 3 year period are
      presented. All of them had anemia and a low platelet count whilst the white blood
      cell count was variable. Presentation with bilateral proptosis and acute febrile
      neutrophilic dermatosis (Sweet's syndrome) were unique features observed in one
      case each. None of these cases could afford specific therapy and thus serve to
      illustrate the natural history of the disease in pediatric practice.

PMID- 8262595
TI  - Sphingomyelinase enzyme assay in Niemann-Pick disease.
AB  - Niemann-Pick group of diseases are rare autosomal recessive disorders of
      lysosomal enzymes. These are divisible into six types depending on clinical and
      biochemical features. On the basis of sphingomyelinase assay in five cases of
      Niemann-Pick disease, three cases were classified as type IA, one as type IS and
      one as type IIS. Their clinicopathological profiles are compared with 17 cases
      reported previously from India.

PMID- 8262596
TI  - Antibiotic associated colitis.
AB  - It is a prospective study based on 100 consecutive cases of diarrhea following
      antibiotic therapy admitted to the pediatric services of J.N. Medical College,
      A.M.U., Aligarh between January to December 1987. They had C. penicillin (50),
      chloramphenicol (34), ampicillin (34), gentamicin (34), cephalosporin (4) and
      cotrimoxazole (4) for 3 days to 3 weeks prior to the onset of diarrhea. Apart
      from routine and special investigations, naked eye and microscopic examination of
      stool, its culture for pathogens including Cl. difficile were carried out in all
      cases. Presence of Cl. difficile cytotoxin was demonstrated by observing the
      cytopathic. Effect on veru cell culture, 18 grew Cl. difficile (14 cyto toxin
      positive). Frequency of fever, vomiting, abdominal distension, dehydration and
      duration of diarrhea was not different (p > 0.05) in the two groups. Purge rate
      and presence of mucus and blood in Cl. difficile positive patients was
      significantly higher (p < 0.05). Eight Cl. difficile positive (7 cytotoxin+ve)
      were subjected to endoscopy. Three of them showed P.M. colitis and 2 non specific
      colitis. Chloromycetin, gentamicin and penicillin were the main culprits
      responsible for AAC. None of the patients given ampicillin alone suffered from
      AAC. The mortality was 5%.

PMID- 8262597
TI  - Sanfilippo syndrome.

PMID- 8262598
TI  - Treatment of severe persistent pulmonary hypertension of newborn with magnesium
      sulfate.

PMID- 8262599
TI  - The effect of phototherapy on total phospholipid levels of red cell membrane in
      jaundiced neonates.

PMID- 8262600
TI  - Calcifying epithelioma (pilomatrixoma) of Malherbe.

PMID- 8262601
TI  - Ciprofloxacin induced hypersensitivity vasculitis syndrome.

PMID- 8262602
TI  - Clonidine casualty.

PMID- 8262603
TI  - Glaucoma surgery: new approaches.

PMID- 8262604
TI  - Current concepts in the diagnosis and management of developmental glaucomas.
AB  - Developmental glaucoma is a global problem and has a broad range of ocular
      manifestations and is sometimes associated with systemic disorders and syndromes.
      It poses a major diagnostic and management problem to the ophthalmologists. A
      proper diagnostic evaluation under general anesthesia is advisable for all
      children who do not cooperate for an office examination. Surgery remains the
      principal therapeutic modality in the management of developmental glaucoma and
      medical therapy is limited to a supplemental role while the child is being
      prepared for surgery. Conventional angle incision surgery (goniotomy and
      trabeculotomy ab externo) is uniquely valuable in the management of primary
      developmental glaucoma, while combined trabeculotomy cum trabeculectomy offers
      the best hope of success in advanced cases. In recent years, artificial drainage
      devices such as the Molteno implant seem to be promising for safe and effective
      pressure control in children with refractory developmental glaucoma. Visual
      rehabilitation involves correction of refractive errors, removal of opacities in
      media (i.e. cataract or corneal scarring) and aggressive amblyopia therapy. Early
      diagnosis, prompt institution of therapy combined with commitment from the family
      for postoperative follow-up care are critical for the restoration of good visual
      function.

PMID- 8262605
TI  - Anterior chamber depth and lens thickness in primary angle-closure glaucoma: a
      case-control study.
AB  - Anterior chamber depth and lens thickness have been considered as important
      biometric determinants in primary angle-closure glaucoma (PACG). In a tertiary
      care centre-based case-control study, 70 patients and equal number of controls
      were investigated to analyse the strength of association and predictability of
      anterior chamber depth (ACD) and lens thickness (LT) in the disease. Mean (+/-
      S.D.) ACD and LT in the cases and the controls were found to be 2.28 +/- 0.19,
      2.87 +/- 0.10; 4.57 +/- 0.34 and 4.13 +/- 0.19 mm respectively. Two sample t test
      demonstrated statistically significant difference in the ACD and LT between the
      cases and the controls (Difference being -0.59, 0.44; 95% confidence interval of
      the difference: -0.64, -0.53 and 0.34, 0.53 respectively, P < 0.01). Logistic
      regression analysis demonstrated statistically significant protective effect of
      ACD over PACG (P < 0.01). The odds ratio corresponding to an increase of 0.01 mm
      in ACD and LT were computed as 0.83 and 1.11 respectively.

PMID- 8262606
TI  - The role of 5-fluorouracil in complicated glaucomas.
AB  - The long-term efficacy of trabeculectomy in controlling intraocular pressure
      (IOP) has been found unsatisfactory in various complicated and refractory
      glaucomas. The most common cause for failure is excessive scarring at the
      filtering site. Several wound modulating agents which reduce scarring have been
      tested. In this study, 5-Fluorouracil (5-FU), a halogenated pyrimidine analogue
      and a potent anti-mitotic agent, was applied for seven days after trabeculectomy
      in eighteen complicated and unsuccessful filtering glaucomas, at a daily dosage
      of 5 mg in the form of 0.5 ml subconjunctival injections. The common
      postoperative complications encountered were corneal epithelial erosion (38%),
      wound leakage (16%), subconjunctival haemorrhage (32%) and hyphaema (10%), all
      during the first 7 to 10 days. Monitoring at regular intervals up to six months
      showed adequate control of IOP (less than 22mm Hg.) in 88% of the cases. Cases of
      aphakic glaucoma and neovascular glaucoma showed poor response. Use of 5-FU as an
      adjuvant to filtering surgery in various complicated glaucomas improves the long
      term results.

PMID- 8262607
TI  - Intraoperative mitomycin C in complicated glaucomas.
AB  - Filtering surgery has been found to be less successful in certain types of
      glaucoma. These include young patients, those with pigmentary glaucoma, secondary
      glaucoma, angle recession glaucoma, aphakic or pseudophakic glaucoma, and
      patients requiring reoperation. This study describes the authors' attempt to
      evaluate the effectiveness of conventional trabeculectomy with intraoperative
      application of mitomycin C in such patients. Ten eyes of 8 patients were
      evaluated in this study. Of these cases 4 eyes (2 bilateral cases) were from the
      primary juvenile open angle group; 2 eyes each had pseudophakic glaucoma and
      previous anti-glaucoma surgery which had failed; one eye had aphakic glaucoma and
      the last suffered from angle recession glaucoma. The intraocular pressure was
      successfully controlled in all the ten eyes. The preoperative IOP ranged from 28
      to 50 mm Hg and the postoperative IOP ranged from 7 to 16 mm Hg. The
      postoperative complications were minimal.

PMID- 8262608
TI  - Releasable suture technique for trabeculectomy.
AB  - We studied the effect of the releasable suture technique on immediate
      postoperative intraocular pressure (IOP). Nine eyes of nine patients with
      glaucoma had trabeculectomy with a releasable suture. In the six eyes that did
      not receive antimitotics, the suture was released by the fifth postoperative day;
      in the others suture release was delayed up to the fourteenth day. Of the nine
      patients, one had an acceptable postoperative IOP and did not need suture
      release; in another the suture broke and could not be released. In the remaining
      seven patients, the difference between the pre-release and post-release IOP was
      statistically significant (p < 0.001). The complications of this technique
      include failed suture release, subconjunctival hematoma and a distinctive
      "windshield wiper" keratopathy.

PMID- 8262609
TI  - Hallermann-Streiff syndrome.

PMID- 8262610
TI  - Penetrating orbitocranial injuries--report of two cases.

PMID- 8262611
TI  - Retained foreign body in orbit with intra cranial extension.

PMID- 8262612
TI  - Pulsating enophthalmos in aplasia of sphenoid wing.

PMID- 8262613
TI  - Practical approach to diagnosis and management of primary glaucomas.

PMID- 8262614
TI  - Reduction in superoxide anion secretion and bactericidal activity of neutrophils
      from aged rats: reversal by the combination of gamma interferon and growth
      hormone.
AB  - Polymorphonuclear neutrophils (PMN) from bone marrow of 24-month-old rats kill
      Escherichia coli less efficiently than PMN from 3-month-old rats. Secretion of O2
      and killing of E. coli by PMN from both young and old rats can be significantly
      augmented by preincubation with either 250 U of gamma interferon (IFN-gamma) or
      250 ng of growth hormone (GH) per ml. This priming is specific, because
      neutralizing monoclonal antibodies against either IFN-gamma or GH completely
      abrogate the enhanced O2- secretion by PMN from young rats. However, in contrast
      to PMN from young rats, PMN from aged rats are not primed to kill E. coli by 10
      fold-lower concentrations of either IFN-gamma (25 U/ml) or GH (25 ng/ml). To
      explore the mechanism for the reduction in bacterial killing by PMN from old
      rats, a syngeneic GH-secreting pituitary cell line (GH3) was implanted in vivo.
      PMN from GH3-treated aged rats, but not control aged rats, could now be primed in
      vitro for O2- secretion by IFN-gamma (25 U/ml). Although PMN from aged rats do
      not respond to the lower doses of either IFN-gamma or GH, the combination of both
      reagents totally restores the ability of PMN to secrete O2- and to kill E. coli.
      This synergistic priming is observed with PMN from aged rats, but not with those
      from young rats, and can be detected when both reagents are added simultaneously
      or when they are added in either sequence. Furthermore, addition of a monoclonal
      antibody against either IFN-gamma or GH abrogates the synergism of these two
      molecules. Collectively, these data identify an important alteration in myeloid
      cells from aged rodents by showing that their PMN are intrinsically unable to
      respond to low concentrations of IFN-gamma by secreting O2- and killing bacteria.
      The results also define a previously unrecognized synergism in PMN from aged
      animals by showing that GH synergizes with IFN-gamma both in vivo and in vitro to
      restore these suppressed responses.

PMID- 8262615
TI  - Protein antigens of Chlamydia psittaci present in infected cells but not detected
      in the infectious elementary body.
AB  - Ocular infection of guinea pigs with the guinea pig inclusion conjunctivitis
      (GPIC) strain of Chlamydia psittaci produces a clinical condition representative
      of acute chlamydial conjunctivitis in humans. Guinea pigs which had recovered
      from two challenges with GPIC were used as a source of sera for the
      identification of antigens present in GPIC-infected tissue culture cells but
      absent in the infectious elementary body (EB). Immunoblots of lysates of infected
      HeLa cells probed with the convalescent-phase sera identified protein antigens of
      22, 34, and 52 kDa (p22, p34, and p52, respectively) that were not detected in
      lysates of purified EB or in uninfected HeLa cells. Protein p22 was also not
      detected in lysates of purified reticulate bodies. Immunoblotting of lysates of
      HeLa cells infected with other chlamydiae demonstrated that the antigenicity of
      p22 and p34 was subspecies specific. Immunoblotting was also used to detect p22
      and p34 in lysates of the conjunctivae of infected guinea pigs. Adsorption of
      convalescent-phase sera with GPIC EB produced a reagent with dominant reactivity
      toward p22, p34, and a 28-kDa EB protein. Immunofluorescent staining of GPIC
      infected HeLa cells demonstrated that these adsorbed sera labeled the inclusion
      and inclusion membrane, with no apparent reactivity toward EB or reticulate
      bodies. Collectively, these data identify non-EB chlamydial components which may
      be released into the inclusion during intracellular growth.

PMID- 8262616
TI  - Phage-associated differences in staphylococcal enterotoxin A gene (sea)
      expression correlate with sea allele class.
AB  - Staphylococcus aureus strains which produced either high or low levels of
      staphylococcal enterotoxin A (SEA) with a minimal eightfold difference between
      the two groups were identified. For FRI100 and FRI281A (prototypes for each
      group), strain differences in the expression of the SEA-encoding gene (sea) were
      found to occur at the level of sea mRNA concentration, and part of the difference
      in expression was associated with the sea-containing phages. Southern blot
      analysis revealed that this phage-associated difference was not due to
      differences in the copy number of sea. Nucleotide sequence analysis of sea from
      FRI281A revealed a new allele of sea, with the majority of the sequence
      differences occurring in the upstream promoter region. Although a strict
      correlation was observed between the level of SEA production and sea allele class
      for several strains, the sequence differences observed in the upstream region
      were not sufficient in themselves to alter the expression level of sea.

PMID- 8262618
TI  - Selective translocation of annexins during intracellular redistribution of
      Chlamydia trachomatis in HeLa and McCoy cells.
AB  - When Chlamydia trachomatis elementary bodies enter epithelial cells, they occupy
      membrane-bound vesicles that aggregate with each other in a calcium-dependent
      manner but that do not fuse with lysosomes. As members of the annexin family of
      calcium- and membrane-binding proteins have been implicated in mediating calcium
      regulated membrane traffic during endo- and exocytosis, we examined the
      intracellular localization of certain annexins following invasion of HeLa and
      McCoy cells by C. trachomatis serovar L2. Immunofluorescence staining with a
      panel of polyclonal antibodies against five human annexins revealed that annexins
      III, IV, and V translocate within the cytoplasm to the proximity of intracellular
      chlamydiae whereas the distribution of annexins I and VI was unaffected. The
      distinct distribution of annexins I and III was further analyzed by confocal
      microscopy, which revealed an intimate association between chlamydial aggregates
      or inclusions and annexin III. Confocal microscopy also confirmed the
      nonassociation of annexin I with chlamydial aggregates. Depletion of
      intracellular Ca2+ did not prevent association of annexin III with individual
      elementary body-containing endosomes but did prevent formation of chlamydial
      aggregates and translocation of annexin III. Furthermore, chloramphenicol-treated
      cells also showed association between chlamydial aggregates and annexin III,
      indicating that the annexins are of host cell origin. These data suggest that
      certain cytosolic annexins may be involved in the Ca(2+)-dependent aggregation
      and fusion of chlamydia-containing vesicles. The fact that these Ca(2+)-binding
      proteins differ in their ability to associate with chlamydia-containing vesicles
      and inclusions implies that the factors that regulate the interaction of annexin
      I and annexin III with membrane are different and suggests a selective regulatory
      mechanism for endosome aggregation and avoiding lysosome fusion during chlamydia
      infection.

PMID- 8262617
TI  - Lipoteichoic acid induces secretion of interleukin-8 from human blood monocytes:
      a cellular and molecular analysis.
AB  - Invasion by gram-positive and gram-negative bacterial organisms is characterized
      immunopathologically by the activation of mononuclear phagocytic cells, leading
      to the elaboration of macrophage-derived regulatory and chemotactic factors, and
      the resultant influx of inflammatory leukocytes. Little is known regarding the
      mechanisms by which gram-positive organisms initiate macrophage activation and
      subsequent inflammation. In this investigation, we postulated that lipoteichoic
      acid (LTA) purified from two different gram-positive bacterial species was an
      important signal for the expression of chemotactic cytokines from human
      peripheral blood monocytes (PBM). In initial experiments, we demonstrated that
      cell-associated interleukin-8 (IL-8) was expressed by mononuclear phagocytes
      present in inflamed areas of endocardium in cases of acute Staphylococcus aureus
      endocarditis. We next demonstrated that LTA purified from either Staphylococcus
      aureus or Streptococcus pyogenes induced the time- and dose-dependent expression
      of IL-8 mRNA and protein from human PBM. The expression of IL-8 mRNA from LTA-
      but not lipopolysaccharide (LPS)-treated PBM was superinduced by concomitant
      treatment with cycloheximide, indicating that the expression of IL-8 mRNA from
      LTA-treated PBM was negatively controlled by repressor proteins. Furthermore,
      mRNA stability studies indicated that IL-8 mRNA was less stable in the presence
      of LTA than in the presence of LPS. Our findings indicate that LTA can induce the
      secretion of the polymorphonuclear leukocyte chemotactic factor IL-8 and that LTA
      may be an important cellular mediator of inflammatory cell recruitment that
      characterizes immune responses to gram-positive bacterial infections.

PMID- 8262619
TI  - Human T-cell responses to Mycoplasma arthritidis-derived superantigen.
AB  - When injected into mice, Mycoplasma arthritidis causes a chronic arthritis that
      resembles rheumatoid arthritis, histologically. The organism produces a
      superantigen termed Mycoplasma arthritidis mitogen or MAM, that in humans
      preferentially expands T cells whose antigen receptors express V beta 17. T cells
      with this phenotype appear to be increased in rheumatoid synovial effusions. We
      describe a novel approach to isolating and characterizing human MAM-reactive T
      cell lines and determining their T-cell receptor (TCR) V beta usage. Lines were
      prepared from T cells that clustered with dendritic cells during a 2-day exposure
      to MAM. Cluster and noncluster fractions of T cells were then expanded by using
      feeder cells and a polyclonal mitogen. Most of the MAM reactivity was found in
      dendritic T-cell clusters, as were most of the T cells expressing TCR V beta 17.
      After expansion, 76% of the cluster-derived T-cell lines were MAM reactive, while
      no reactivity was seen in cell lines derived from the noncluster fraction. Of the
      MAM-reactive lines, 49% expressed V beta 17 on some or all of the cells. Cell
      lines from both cluster and noncluster fractions were analyzed for TCR V beta
      mRNA expression by PCR amplification. Other V beta genes (5.1, 7, 8, 12, and 20)
      were found to be expressed by lines that were MAM reactive, although these were
      not a major component of the cluster-derived T cells. Some non-cluster-derived
      lines expressed V beta s 17, 12, and 7, but these proved to be nonreactive to
      MAM. Therefore, dendritic cells can be used to immunoselect and characterize T
      cells that express superantigen-reactive TCRs.

PMID- 8262620
TI  - Effect of treatment on titer, function, and antigen recognition of serum
      antibodies to Actinobacillus actinomycetemcomitans in patients with rapidly
      progressive periodontitis.
AB  - Although periodontal treatment by scaling and root planing (SCRP) is known to
      induce bacteremia, the effect of this procedure on the host immune response is
      not known. We have determined pre- and post-SCRP immunoglobulin G antibody titers
      to antigens of Actinobacillus actinomycetemcomitans in the sera of 22 patients
      with rapidly progressive periodontitis. We also assessed the ability of these
      sera to enhance phagocytosis and killing of A. actinomycetemcomitans by human
      polymorphonuclear leukocytes by using a polymorphonuclear leukocyte
      chemiluminescence (CL) assay. Specific anti-A. actinomycetemcomitans antibody
      titers were significantly increased at 6 and 12 months after beginning treatment,
      and CL values were significantly increased at 12 months, whereas mean
      interproximal pocket depths were significantly decreased at 12 months after
      beginning treatment. When patients were classified as either seropositive (twice
      the median titer of control subjects; n = 10) or seronegative (n = 12), both
      median titers and CL values were significantly increased for the seronegative
      group at 6 and 12 months after treatment. In the seropositive group, only the
      median titer was significantly increased at 12 months. Western blot (immunoblot)
      patterns for six seronegative and six seropositive patients differed remarkably
      at the baseline. Before treatment, all of the seropositive patients recognized
      high-molecular-mass lipopolysaccharide (LPS) and a large number of protein
      components. Patterns were virtually unaffected by therapy. Before treatment, only
      one of the seronegative patients recognized the LPS smear and none reacted
      strongly with protein components. Following treatment, slight LPS staining was
      observed for five of six seronegative patients and detection of protein bands was
      enhanced in all cases. We conclude that treatment by SCRP induces a humoral
      immune response, especially in seronegative patients, and that response may play
      a role in the observed beneficial effects of periodontal treatment.

PMID- 8262621
TI  - Induction of specific immunoglobulin A in the small intestine, colon-rectum, and
      vagina measured by a new method for collection of secretions from local mucosal
      surfaces.
AB  - In order study patterns of local antibody responses following mucosal
      immunization of mice via different routes, a method for collection of secretions
      directly from mucosal surfaces was developed. Mice were immunized on days 0, 10,
      17, and 24 by administration of cholera toxin into the oral cavity, stomach,
      colon-rectum, or vagina. At sacrifice on day 32, absorbent wicks were placed in
      the oral cavity and, via an applicator tube, into the vagina and distal colon
      rectum and along the entire small intestine after flushing of luminal contents.
      Protein was quantitatively extracted from wicks, and specific anti-cholera toxin
      immunoglobulin A (IgA) and IgG were measured by enzyme-linked immunosorbent
      assay. Concentrations of specific IgA in secretions at various mucosal sites were
      dramatically influenced by the route of immunization. Oral immunization
      effectively induced IgA in saliva, and the intragastric route was optimal for
      induction of IgA in the small intestine. High levels of specific IgA appeared on
      the colonic-rectal mucosal surface only after rectal delivery of antigen. Oral,
      gastric, and rectal immunizations also produced distant responses in the vagina.
      Following vaginal immunization, however, neither local nor distant IgA responses
      were detected. These results suggest that vaccines intended for protection of
      colonic-rectal and vaginal mucosal surfaces might best be administered by the
      rectal route.

PMID- 8262622
TI  - The Staphylococcus aureus collagen adhesin is a virulence determinant in
      experimental septic arthritis.
AB  - The importance of a collagen-binding adhesin in the pathogenesis of septic
      arthritis has been examined by comparing the virulence of two sets of
      Staphylococcus aureus mutants in an animal model. Collagen adhesin-negative
      mutant PH100 was constructed by replacing the chromosomal collagen adhesin gene
      (cna) in a clinical strain, Phillips, with an inactivated copy of the gene.
      Collagen adhesin-positive mutant S. aureus CYL574 was generated by introducing
      the cna gene into CYL316, a strain that normally lacks the cna gene. Biochemical,
      immunological, and functional analyses of the generated mutants and their
      respective parent strains showed that binding of 125I-labeled collagen,
      expression of an immunoreactive collagen adhesin, and bacterial adherence to
      cartilage were directly correlated with the presence of a functional cna gene.
      Greater than 70% of the mice injected with the Cna+ strains developed clinical
      signs of arthritis, whereas less than 27% of the animals injected with Cna-
      strains showed symptoms of disease. Furthermore, mice injected with the Cna+
      strain Phillips had remarkably elevated levels of immunoglobulin G1 and
      interleukin-6 compared with mice injected with the Cna- mutant PH100. Taken
      together, these results demonstrate that collagen adhesin plays an important role
      in the pathogenesis of septic arthritis induced by S. aureus.

PMID- 8262623
TI  - Inactivation of Escherichia coli penicillin-binding proteins by human
      neutrophils.
AB  - Neutrophils use a variety of microbicidal mechanisms in their role as one of the
      primary arms of the human host defense system. We have previously observed that a
      cell-free system containing myeloperoxidase (MPO), one of the major components of
      the neutrophil's oxidative antimicrobial systems, inactivated microbial
      penicillin-binding proteins (PBPs), which mediate the formation of the
      peptidoglycan layer of eubacterial cell walls. This is a potentially important
      mechanism of MPO-mediated bacterial toxicity. Since numerous other microbicidal
      systems, both oxidative and nonoxidative, are used by whole neutrophils, we
      investigated the effect of intact neutrophils on Escherichia coli PBPs.
      Penicillin binding activity was progressively reduced by neutrophil exposure for
      all PBPs. Loss of penicillin binding activity correlated well with loss of
      microbial viability for almost all PBPs. Azide-treated neutrophils, MPO-deficient
      neutrophils, and chronic granulomatous disease neutrophils inactivated E. coli
      PBPs in a manner similar to that of normal neutrophils, suggesting that MPO
      independent, and even oxygen-independent, microbicidal systems are also involved
      in inactivation of PBPs. PBP inactivation, an antimicrobial strategy used by beta
      lactam-producing molds (and now by physicians), may be an important microbicidal
      mechanism used by human neutrophils.

PMID- 8262624
TI  - Demonstration and characterization of simultaneous production of a thermostable
      direct hemolysin (TDH/I) and a TDH-related hemolysin (TRHx) by a clinically
      isolated Vibrio parahaemolyticus strain, TH3766.
AB  - Simultaneous production of a thermostable direct hemolysin (TDH)-like toxin
      (TDHx) and a TDH-related hemolysin (TRH)-like toxin (TRHx) by a clinical isolate
      (strain TH3766) of Kanagawa phenomenon-positive Vibrio parahaemolyticus was
      demonstrated and characterized. The two hemolysins were differentially purified
      by column chromatography on hydroxyapatite and immunoaffinity columns. The
      molecular weight of the two hemolysins were estimated to be 23,000 by sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE). The purified TDHx was
      indistinguishable from the previously reported TDH/I (from strain TH012) but was
      different from the authentic TDH of a Kanagawa phenomenon-positive strain (T4750)
      physicochemically. The mobility of TRHx in nondenaturing PAGE differed from all
      the known TDHs and TRHs. The genes (tdhX and trhX) coding for TDHx and TRHx were
      cloned and sequenced. Homologies of nucleotide sequences of the coding regions
      between tdhX and tdhA (a gene for the authentic TDH) and between trhX and trh (a
      gene for the authentic TRH) were 98.1 and 99.1%, respectively, and homology
      between tdhX and trhX was 68.1%. At the amino acid level, TdhX was completely
      identical to TDH/I, although two base differences were found in the nucleotide
      sequences between tdhX and tdh/I. Two amino acid differences were observed
      between TrhX and Trh. Thus, these findings suggest that the TH3766 strain
      produces two types of hemolysins simultaneously. This is the first evidence that
      a strain of V. parahaemolyticus produces two types of toxins of the TDH-TRH
      family at the same time.

PMID- 8262625
TI  - Enterotoxic activity of Klebsiella oxytoca cytotoxin in rabbit intestinal loops.
AB  - We examined the enterotoxicity of a Klebsiella oxytoca cytotoxin which is
      produced by K. oxytoca OK-1, a strain from a patient with antibiotic-associated
      hemorrhagic colitis. Injection of the cytotoxin into ligated ileal and colonic
      loops in rabbits caused the accumulation of fluid in the loops. The fluid was
      bloody in the ileal loops but not in the colonic ones. Histological examination
      revealed intense mucosal hemorrhage with erosion in the ileum, whereas no
      microscopic change was noted in the colon. The fluid accumulation was shown to be
      a dose-dependent response in both ileal and colonic loops. The amounts of the
      cytotoxin required for maximal fluid accumulation in ileal and colonic loops were
      60 and 10 micrograms, respectively. Fluid accumulation was first noticeable in
      ileal loops 12 h and in colonic ones 5 h after the injection of these doses of
      the cytotoxin and then proceeded with time. When K. oxytoca OK-1, a cytotoxin
      producing strain, was inoculated into the loops at doses of 1 x 10(8) and 5 x
      10(9) CFU, similar fluid accumulation was observed. However, inoculation of K.
      oxytoca ATCC 13182, a non-cytotoxin-producing strain, at the same doses did not
      cause any change. These results suggest that the cytotoxin-producing strain of K.
      oxytoca is the causative organism of antibiotic-associated hemorrhagic colitis
      and that the toxin is the factor responsible for pathogenesis.

PMID- 8262626
TI  - Conservation of salivary glycoprotein-interacting and human immunoglobulin G
      cross-reactive domains of antigen I/II in oral streptococci.
AB  - In this study we localized more precisely the salivary glycoprotein-interacting
      and the human immunoglobulin G (hIgG)-cross-reacting domains on the SR molecule,
      an antigen I/II-related protein from S. mutans serotype f. Mapping of the SR
      molecule with polypeptides expressed by subclones covering the entire molecule
      and with synthetic peptides demonstrates that the salivary glycoprotein-binding
      domain is located in the N-terminal alanine-rich repeats of the SR molecule. In
      order to investigate the degree of conservation of both regions in various oral
      streptococci, we tested the reactivity of 8 representative strains of the mutans
      group and 11 nonmutans oral Streptococcus strains (S. anginosus, S. milleri, S.
      constellatus, S. intermedius, S. mitis, S. sanguis, S. gordonii, S. salivarius,
      and S. mitis strains) with antipeptide antibodies in a whole-cell enzyme linked
      immunosorbent assay together with colony hybridization analysis using DNA probes
      designed to map these two regions. All the mutans group strains except S. rattus
      and the 11 nonmutans streptococcal strains showed a high conservation of the C
      terminal part of the SR molecule, especially the hIgG-cross-reacting domain, and
      less homology for the N-terminal salivary glycoprotein-binding region. Almost all
      of the sera from patients with rheumatic disease reacted strongly with SR from S.
      mutans serotype f, P1 from S. mutans serotype c, and four peptides located in the
      hIgG-cross-reacting region and not with peptides located at the C and N termini
      and in the proline-rich repeats. These results confirm that epitopes located
      within this region are immunogenic in humans and could lead to the synthesis of
      natural anti-IgG antibodies.

PMID- 8262627
TI  - Direct activity of human T lymphocytes and natural killer cells against
      Cryptococcus neoformans.
AB  - Lymphocytes constitute a critical component of host defenses against
      cryptococcosis. Previously, we demonstrated that human lymphocytes cultured with
      interleukin-2 formed conjugates with, and directly inhibited the growth of,
      Cryptococcus neoformans. Here, we explore the anticryptococcal activity of
      freshly isolated, highly purified populations of human peripheral blood
      lymphocytes. Lymphocytes were incubated with encapsulated C. neoformans for 24 h,
      after which the lymphocytes were lysed, dilutions and spread plates were made,
      and CFU were counted. Fungistasis was determined by comparing growth in wells
      with and without lymphocytes. Nylon wool-nonadherent peripheral blood mononuclear
      cells (NWNA PBMC) were highly fungistatic, even if either T cells or natural
      killer (NK) cells were depleted by panning. A mixed population of T cells and NK
      cells, obtained by rosetting NWNA PBMC with sheep erythrocytes, completely
      inhibited cryptococcal growth, whereas the nonrosetting cells had little
      fungistatic activity. CD4+, CD8+, and CD16/56+ lymphocytes, isolated by positive
      immunoselection, had potent growth-inhibitory activity. In contrast, purified B
      cells had no activity. Fungistasis was seen even in the absence of opsonins.
      Antifungal activity was markedly diminished when surface receptors on NWNA PBMC
      were cleaved by treatment with trypsin or bromelain. Supernatants from stimulated
      lymphocytes or concentrated lymphocyte sonicates were not active. Lymphocyte
      mediated fungistasis was seen with two different strains of C. neoformans. CD4+,
      CD8+, and CD16/56+ lymphocytes formed conjugates with C. neoformans, as observed
      under Nomarski differential interference contrast microscopy and videomicroscopy.
      These data demonstrate that freshly isolated peripheral blood T cells and NK
      cells have the capacity to bind and directly inhibit the growth of C. neoformans.

PMID- 8262628
TI  - Conformationally appropriate expression of the Toxoplasma antigen SAG1 (p30) in
      CHO cells.
AB  - The Toxoplasma gondii major surface antigen, called SAG1 or p30, is a highly
      immunogenic protein which has generated great interest as a diagnostic reagent,
      as a potential subunit vaccine, and for its role in invasion. Unfortunately,
      bacterial recombinant protein is grossly misfolded so that, for example, it is
      not effectively recognized by antibodies to native SAG1. To overcome this, we
      have turned to expression in CHO cells, using cotransfection of the SAG1 gene and
      the mouse dihydrofolate reductase (DHFR) gene into CHO cells that are DHFR-. SAG1
      expression was amplified by methotrexate coselection of CHO cells in combination
      with fluorescence-activated cell sorting for SAG1 expression. The resulting
      population expressed recombinant SAG1 that is recognized by antiserum specific
      for natural, nonreduced SAG1, indicating that, unlike in bacteria, expression in
      CHO cells results in proper folding. Processing was at least partially correct in
      that, like natural SAG1, recombinant SAG1 was attached to the plasma membrane via
      a glycolipid anchor, although tunicamycin treatment was necessary to prevent N
      glycosylation (SAG1 is not glycosylated in the parasite but does have a consensus
      N-linked site). Finally, purified recombinant SAG1 was recognized by human sera
      known to be reactive to toxoplasma proteins, indicating that this material has
      potential as a diagnostic reagent and possibly as a component of a subunit
      vaccine.

PMID- 8262629
TI  - Comparison of conjugates composed of lipopolysaccharide from Shigella flexneri
      type 2a detoxified by two methods and bound to tetanus toxoid.
AB  - Shigella flexneri type 2a lipopolysaccharide (LPS) was detoxified with acetic
      acid (O-SP) or with hydrazine (DeALPS). DeALPS, but not O-SP, retained part of
      its lipid A. Both gave an identical line of precipitation with typing antiserum
      by double immunodiffusion, and both had low levels of LPS activity by the Limulus
      amoebocyte lysate assay. O-SP had an M(r) of approximately 17,000. DeALPS had two
      components of M(r)s approximately 30,00 (major and approximately 10,000 (minor).
      Adipic acid hydrazide derivatives of O-SP and DeALPS were conjugated to tetanus
      toxoid (TT), purified by gel filtration through CL-6B Sepharose, and designated O
      SP-TT and DeALPS-TT, respectively. Saccharide (2.5 micrograms) as O-SP, DeALPS,
      or their conjugates was injected subcutaneously into 5-week-old mice three times
      2 weeks apart. The mice were bled before the second injection and 7 days after
      the second and third. O-SP alone did not elicit immunoglobulin M (IgM) or IgG LPS
      antibodies. DeALPS elicited low levels of IgM LPS antibodies after the third
      injection only. Two of three lots of O-SP-TT induced significant levels of IgM
      LPS antibodies after the third injection. One O-SP-TT lot elicited IgG LPS
      antibodies after the second injection, and all three lots elicited significant
      levels of IgG after the third. DeALPS-TT induced low levels of anti-LPS IgM and
      IgG only after the third injection. The geometric mean antibody titers of both
      immunoglobulin classes induced by O-SP-TT were higher than those induced by
      DeALPS-TT. By these criteria, O-SP provided a more immunogenic saccharide than
      DeALPS for S. flexneri type 2a conjugates.

PMID- 8262630
TI  - Occurrences, specificities, and functions of ubiquitous antibodies in human serum
      that are reactive with the Cryptococcus neoformans cell wall.
AB  - Previous studies found that normal human serum (NHS) contains an immunoglobulin G
      (IgG) antibody that mediates initiation of the classical complement pathway by
      nonencapsulated Cryptococcus neoformans. The present study used an enzyme-linked
      immunosorbent assay with whole nonencapsulated yeast cells as solid-phase
      antigens to demonstrate the presence of high levels of IgG antibody in each of 11
      sera from normal adult donors. The IgG antibodies were of the IgG2 subclass. The
      antibody activity was blocked completely by treatment of serum with isolated
      yeast glucan. Treatment of serum with mannan or chitin had no effect on antibody
      levels. Antibody activity was adsorbed completely by treatment of serum with
      zymosan particles. Adsorption with intact cells of Saccharomyces cerevisiae or
      Candida albicans had no effect, suggesting that the glucan on S. cerevisiae or C.
      albicans is not surface exposed. Assessment of the opsonic requirements for
      phagocytosis of nonencapsulated cryptococci by monocyte-derived human macrophages
      (MO-M phi) showed that high levels of phagocytosis occurred when yeast cells were
      opsonized with NHS. Removal of anti-glucan antibody by adsorption with whole
      nonencapsulated cryptococci did not diminish opsonic activity. Heat-inactivated
      serum or anti-glucan antibody affinity purified from NHS lacked opsonic activity.
      Taken together, these results indicate that phagocytosis of nonencapsulated
      cryptococci by monocyte-derived human macrophages has an obligatory requirement
      for opsonic ligands of the complement system, with no contribution by the anti
      glucan IgG that is found in NHS.

PMID- 8262631
TI  - Toxoplasma encephalitis in congenic B10 and BALB mice: impact of genetic factors
      on the immune response.
AB  - Factors which determine the pathogenesis and course of Toxoplasma encephalitis
      are poorly understood. In the present study, the influence of genetic factors in
      congenic B10 and BALB mice of H-2q, H-2k, and H-2b haplotypes was examined
      following oral infection with a low-virulence strain of Toxoplasma gondii (DX).
      There were striking differences among these strains. Whereas B10 mice were highly
      susceptible, BALB mice had a less severe and more protracted disease. In all
      animals with a fatal outcome, Toxoplasma encephalitis was the cause of death.
      Within the two congenic groups, the major histocompatibility complex haplotype
      had a strong impact on the disease. The H-2k haplotype was associated with early
      death in B10 mice but with a favorable outcome in BALB mice, whereas the reverse
      was observed for the H-2q haplotype. These findings indicate that genetically
      determined factors are critically involved in determining the intracerebral
      immune response and the course of murine toxoplasmosis. Some of these factors
      appear to be associated with the major histocompatibility complex haplotype, but
      significant differences between B10 and BALB mice point to a modulating role of
      additional genetic loci. Immunohistochemical studies and cytokine analyses of
      cerebrospinal fluid and serum revealed significant differences in the
      intracerebral immune response between susceptible and resistant strains. A poor
      outcome was associated with a large number of intracerebral parasites,
      significant tissue necrosis, a reduced number of intracerebral CD4+ T cells, low
      intrathecal tumor necrosis factor levels, and, to a lesser extent, a reduced
      number of intracerebral CD8+ T cells.

PMID- 8262632
TI  - Cellular and humoral immune responses in dogs experimentally and naturally
      infected with Leishmania infantum.
AB  - In this paper we describe a number of immunological parameters for dogs with a
      chronic Leishmania infantum infection which exhibit patterns of progressive
      disease or apparent resistance. The outcome of infection was assessed by
      isolation of parasites, serum antibody titers to Leishmania antigen, and
      development of clinical signs of leishmaniasis. Our studies show that 3 years
      after experimental infection, asymptomatic or resistant dogs responded to L.
      infantum antigen both in lymphocyte proliferation assays in vitro and in delayed
      type hypersensitivity reaction, whereas no serum antibodies to parasite antigen
      were shown. In contrast, symptomatic or susceptible animals failed to respond to
      parasite antigen in cell-mediated assays both in vitro and in vivo and showed
      considerably higher serum antibodies to leishmanial antigens. In addition,
      significantly higher level of interleukin 2 (IL-2) and tumor necrosis factor were
      found in supernatants from stimulated peripheral mononuclear cells from
      asymptomatic dogs compared with those from symptomatic and control uninfected
      dogs. IL-6 production did not vary significantly among the groups studied.
      Finally, we observed similar results with a group of mixed-breed dogs with
      natural Leishmania infections also grouped as asymptomatic or symptomatic on the
      basis of clinical signs of canine visceral leishmaniasis. These results
      demonstrate that serum antibody titers, antigen-specific proliferative responses,
      delayed-type hypersensitivity skin reactions, and IL-2 and tumor necrosis factor
      production by peripheral mononuclear cells can be used as markers of disease
      progression.

PMID- 8262633
TI  - Biochemical analysis of the membrane and soluble forms of the complement
      regulatory protein of Trypanosoma cruzi.
AB  - A developmentally regulated, 160-kDa trypomastigote surface glycoprotein was
      previously shown to bind the third component of complement and to inhibit
      activation of the alternative complement pathway, thus providing the parasites a
      means of avoiding the lytic effects of complement. We now show that this
      complement regulatory protein (CRP) binds human C4b, a component of the classical
      pathway C3 convertase, and may therefore also act to restrict classical
      complement activation. Characterization of the extent of carbohydrate
      modification of the protein revealed extensive N-linked glycosylation and no
      apparent O-linked sugars. The CRP purified from parasites treated with an
      inhibitor of N-linked glycosylation exhibited a decreased binding affinity for
      C3b compared with that of the fully glycosylated protein. We have previously
      shown that the protein was anchored to the membrane via a glycosyl
      phosphatidylinositol linkage and was spontaneously shed from the parasite
      surface. The spontaneous release of CRP from the parasite surface may augment the
      protection of the parasites from complement-mediated lysis by the removal of
      complement-CRP complexes. The majority of the shed CRP had an apparent molecular
      mass of 160 kDa and lacked the glycolipid anchor, whereas the membrane form was
      recovered with the glycolipid anchor attached and had an apparent molecular mass
      of 185 kDa. Both the membrane form (185 kDa) and the soluble form (160 kDa)
      retained binding affinity for C3b. Evidence is presented to indicate that the
      conversion of the 185-kDa membrane form to the 160-kDa form is the result of
      cleavage by an endogenous phospholipase C.

PMID- 8262634
TI  - Binding of the glycan of the major outer membrane protein of Chlamydia
      trachomatis to HeLa cells.
AB  - Recent studies have shown that the major outer membrane protein (MOMP) of
      Chlamydia trachomatis is glycosylated. The glycan of the MOMP of C. trachomatis
      serovar L2 was separated from the glycoprotein with N-glycanase, reduced with
      tritiated NaBH4, and tested for its ability to interact with HeLa cells. The
      [3H]glycan was shown to attach readily to HeLa cells at 25 or 37 degrees C. This
      process was slower at 4 degrees C. Competition for possibly similar receptor
      sites on HeLa cells between the glycan and a sugar, an aminosaccharide, or
      elementary bodies (EBs) was then studied. D-Galactose, D-mannose, or N
      acetylglucosamine was shown to reduce the attachment of the glycan to HeLa cells
      at concentrations of 0.1 to 0.5 M. Sedoheptulose, D-fructose, or sialic acid did
      not inhibit the binding of glycan to HeLa cells. The presence of at least 100
      native or UV-inactivated EBs per HeLa cell interfered with the glycan's ability
      to bind to HeLa cells. Heat-inactivated EBs did not compete with the glycan for
      binding. In the reverse situation, nonradiolabeled glycan prevented the EBs from
      infecting and forming inclusions in HeLa cells. Incubation of [3H]glycan with
      rabbit immune serum prepared against antigens of whole EB and the MOMP inhibited
      attachment. In contrast, incubation of glycan with mouse monoclonal antibodies
      against the protein portion of the MOMP or the chlamydial lipopolysaccharide did
      not inhibit attachment. These results suggest that the glycan portion of the MOMP
      is involved in the attachment process of C. trachomatis organisms to HeLa cells.

PMID- 8262635
TI  - Cloning and sequencing of the genes encoding Escherichia coli cytolethal
      distending toxin.
AB  - Escherichia coli strains expressing cytolethal distending toxin (CDT) cause
      elongation of CHO cells at 24 h, followed by progressive cellular distention and
      death for up to 120 h. Similar distention and cytotoxicity are seen in HeLa, HEp
      2, and, to a lesser extent, Vero cells. The initial elongation in CHO cells is
      indistinguishable from that caused by E. coli heat-labile toxin (LT). In contrast
      to those from LT strains, supernatants from these strains have no effect on Y-1
      adrenal cells. TnphoA was introduced into CDT-positive E. coli E6468/62
      (O86:H34), isolated from a child with diarrhea, and 13 CDT-negative
      transconjugants were identified. DNA probes constructed from DNA flanking the
      TnphoA insertion sites of CDT-negative mutants were used to identify a CDT
      positive clone from an E6468/62 genomic library with a 5.5-kb insert. Exonuclease
      deletions were created and assayed in CHO cells. In this manner, a 2.3-kb CDT
      active region was defined, and the nucleotide sequence was determined. Sequence
      analysis identified three open reading frames (ORFs), designated cdtA, cdtB, and
      cdtC. These contain 711, 819, and 570 bp, respectively, and encode polypeptides
      with predicted molecular masses of 25.5, 29.8, and 20.3 kDa, respectively. Each
      ORF has a putative signal sequence, and there are 4-bp overlaps between cdtA and
      cdtB and between cdtB and cdtC. The nucleotide and predicted amino acid sequences
      have no significant homology with those of any previously reported genes or
      proteins. By in vitro transcription-translation and an anti-alkaline phosphatase
      immunoblot, native proteins and/or fusion proteins corresponding to each ORF were
      identified.

PMID- 8262636
TI  - Characterization of a Mycobacterium leprae antigen related to the secreted
      Mycobacterium tuberculosis protein MPT32.
AB  - Secreted proteins may serve as major targets in the immune response to
      mycobacteria. To identify potentially secreted Mycobacterium leprae antigens,
      antisera specific for culture filtrate proteins of Mycobacterium tuberculosis
      were used to screen a panel of recombinant antigens selected previously by
      leprosy patient sera. Four potentially secreted antigens were identified by this
      approach, and one was recognized by antibodies specific for MPT32, a secreted M.
      tuberculosis protein. The DNA coding for the M. leprae antigen, which we have
      designated 43L, was isolated and characterized and found to encode a 25.5-kDa
      protein that is preceded by a consensus signal peptide of 39 amino acids. The N
      terminal amino acid sequence of 43L shows 50% homology with the 20 known N
      terminal amino acids of MPT32, and 47% homology was found with the N terminus of
      a 45/47-kDa antigen complex identified in Mycobacterium bovis BCG. These findings
      indicate that 43L represents an antigen related to MPT32 and the M. bovis BCG
      45/47-kDa complex and that 43L is likely to be a protein secreted by M. leprae.
      Purified recombinant 43L protein is recognized by antibodies and T cells from
      healthy contacts and leprosy patients, illustrating that secreted proteins are of
      importance in the immune response to M. leprae.

PMID- 8262637
TI  - Effect of lipopolysaccharide (LPS) chain length on interactions of
      bactericidal/permeability-increasing protein and its bioactive 23-kilodalton NH2
      terminal fragment with isolated LPS and intact Proteus mirabilis and Escherichia
      coli.
AB  - The target-specific cytotoxicity for gram-negative bacteria and the endotoxin
      neutralizing activity of the 55-kDa bactericidal/Permeability-increasing protein
      (BPI) and its bioactive 23-kDa NH2-terminal fragment depend on the strong
      attraction of BPI for the lipid A region of lipopolysaccharides (LPS). We have
      shown before that smooth gram-negative bacteria with long-chain LPS are more
      resistant to BPI (especially holo-BPI) than are rough strains. It has been
      suggested that the high BPI resistance of some gram-negative bacteria, such as
      Proteus mirabilis, might also reflect the structural diversity of lipid A. To
      explore this possibility, we compared the antibacterial activity and binding of
      natural and recombinant holo-BPI and a recombinant NH2-terminal fragment (rBPI
      23) to an isogenic rough (Re-LPS chemotype) and a smooth (S-LPS chemotype) strain
      of P. mirabilis and to LPS isolated from the two strains. Holo-BPI and rBPI-23
      were both potently active against the Re strain of P. mirabilis (90% lethal dose,
      20 nM). In contrast, the smooth strain was > or = 100 times more resistant to
      holo-BPI but only 10 times more resistant to rBPI-23. rBPI-23 was also more
      potent against several Escherichia coli strains from clinical bacteremia
      isolates. Differences in the antibacterial potency of BPI toward the Re and S
      strains of P. mirabilis correlated with differences in the binding of holo-BPI
      and rBPI-23 to these bacteria. In contrast, the binding of biosynthetically (in
      vitro transcribed and translated) 35S-labeled holo-BPI and NH2-terminal fragment
      to isolated Re- and S-LPS from P. mirabilis in solution was similar. Moreover, in
      the Limulus amebocyte lysate assay, holo-BPI and rBPI-23 potently neutralized
      both forms of LPS with equal effectiveness. Together, these results strongly
      suggest that BPI recognizes Proteus lipid A and that the relative resistance of
      (smooth) P. mirabilis to holo-BPI is due to the inhibitory effect of long
      polysaccharide chains of tightly packed LPS in the envelope.

PMID- 8262638
TI  - 2-Deoxy-D-glucose inhibits intracellular multiplication and promotes
      intracellular killing of Legionella pneumophila in A/J mouse macrophages.
AB  - Legionella pneumophila can grow intracellularly in A/J mouse macrophages. 2-Deoxy
      D-glucose (2dG) (0.1, 1, and 10 mM) inhibited intracellular multiplication and
      promoted intracellular killing of L. pneumophila dose dependently when it was
      added to the culture medium of macrophage monolayers, whereas it did not inhibit
      the bacterial growth in buffered yeast extract broth, which was used for an L.
      pneumophila culture. The effect of 2dG was reversible because the surviving
      bacteria resumed intracellular multiplication after the washing away of 2dG from
      the culture. The effect of 2dG was also competitively inhibited by high
      concentrations of glucose. The inhibitory effect of 2dG was not attributed to the
      inhibition of bacterial phagocytosis by macrophages. Furthermore, sodium fluoride
      (0.1 and 1 mM), cycloheximide (0.1 and 1 microgram/ml), and tunicamycin (1, 2,
      and 5 micrograms/ml) did not promote the killing of L. pneumophila in
      macrophages, implying that the inhibitory effect of 2dG cannot be attributed to
      the inhibition of glycolysis, protein synthesis, and protein glycosylation in
      macrophages. We suggest that 2dG promotes intracellular killing of L. pneumophila
      by activating some novel killing mechanism of macrophages.

PMID- 8262639
TI  - Characterization of the low-molecular-mass proteins of virulent Treponema
      pallidum.
AB  - We previously demonstrated that Treponema pallidum cells incubated in vitro in
      the presence of heat-inactivated normal rabbit serum (HINRS) synthesize, in very
      small quantities, several pathogen-specific, low-molecular-mass proteins that
      appear to be localized extracellularly. In this study, we have taken advantage of
      our ability to metabolically radiolabel T. pallidum cells to high specific
      activity to further characterize these antigens. We found that the low-molecular
      mass proteins are not related to the 15- and 17-kDa detergent-phase proteins (J.
      D. Radolf, N. R. Chamberlain, A. Clausell, and M. V. Norgard, Infect. Immun.
      56:490-498, 1988). The low-molecular-mass proteins did not incorporate 3H-labeled
      fatty acids and were not precipitated by rabbit immunoglobulin G (IgG) antibodies
      directed against glutathione S-transferase fusions to the nonlipidated 15- and 17
      kDa proteins. We prepared polyclonal antisera to the low-molecular-mass proteins
      by immunizing two rabbits with the concentrated supernatant of T. pallidum cells.
      IgG antibodies present in the sera of both rabbits precipitated a 21.5-kDa
      protein from solubilized extracts of T. pallidum supernatant and cells. IgG
      antibodies in the serum of the second rabbit precipitated an additional 15.5-kDa
      low-molecular-mass protein only from solubilized extracts of supernatant. While
      investigating the effect of eliminating HINRS from the extraction medium, we
      observed that the low-molecular-mass proteins remained associated with treponemal
      cells that were incubated in the absence of HINRS. These proteins could be eluted
      from the cells by the addition of HINRS or rabbit serum albumin, suggesting that
      they are located on or near the treponemal cell surface. The 15.5- and 21.5-kDa
      low-molecular-mass proteins were not washed off treponemal cells with buffer
      containing 1 M KCl. Experiments employing selective solubilization of the T.
      pallidum outer membrane with 0.1% Triton X-114 and proteinase K accessibility
      indicated that the 15.5-kDa protein, but not the 21.5-kDa protein, is cell
      surface exposed.

PMID- 8262640
TI  - A role for natural antibody in the pathogenesis of leprosy: antibody in nonimmune
      serum mediates C3 fixation to the Mycobacterium leprae surface and hence
      phagocytosis by human mononuclear phagocytes.
AB  - We have previously determined that complement receptors on human mononuclear
      phagocytes and complement component C3 in nonimmune serum mediate phagocytosis of
      the intracellular bacterial pathogen Mycobacterium leprae, the agent of leprosy.
      We have also determined that C3 fixes selectively to the major surface glycolipid
      of M. leprae, phenolic glycolipid 1 (PGL-1). In this study, we have explored the
      role of natural antibody in nonimmune serum in C3 fixation and C1q binding to M.
      leprae and PGL-1. At serum concentrations within the range at which phagocytosis
      of M. leprae is maximal, C3 fixation was mediated by both the classical and the
      alternative complement pathways. At the low end of this serum concentration range
      (2.5%), C3 fixation was mediated predominantly by the classical pathway.
      Consistent with a role for both pathways, C3 fixation to M. leprae was enhanced
      by the addition of either pure C1q to C1q-depleted serum or pure factor B to
      factor B-depleted serum. C3 fixation to M. leprae was strictly antibody dependent
      regardless of the serum concentration used. C3 fixation to M. leprae occurred in
      nonimmune serum but not in agammaglobulinemic serum unless heat-inactivated
      nonimmune serum or small amounts of pure immunoglobulin G (IgG) or IgM were
      added. C3 fixation by both the alternative and the classical complement pathways
      was mediated by antibody, and the antigen-binding portion of the antibody
      molecule was required. C3, IgG, IgM, and C1q were readily detected on the surface
      of M. leprae. Consistent with the previously demonstrated exclusive role of the
      classical complement pathway in C3 fixation to PGL-1, C1q bound to PGL-1 in a
      dose-dependent fashion; C1q binding was evident in > 1.25% nonimmune serum. C1q
      binding to PGL-1 was strictly antibody dependent. When PGL-1 was incubated with
      pure C1q, little or no C1q bound to PGL-1 unless heat-inactivated nonimmune serum
      or pure IgG or IgM was added. When PGL-1 was incubated in nonimmune serum, C3
      bound directly to PGL-1 and not to anti-PGL-1 antibody, since the amount of C3
      bound to PGL-1 was not reduced by acid elution of the antibody. However, the
      amount of C3 bound to PGL-1 was markedly reduced by hydroxylamine treatment,
      providing evidence for C3 fixation via a covalent ester bond. Nonimmune serum
      contained antibody to all four major M. leprae surface carbohydrates. Relative to
      PGL-1, nonimmune serum contained more antibody to the other surface
      carbohydrates.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8262641
TI  - Depression of liver metabolism and induction of cytokine release by diphtheria
      and tetanus toxoids and pertussis vaccines: role of Bordetella pertussis cells in
      toxicity.
AB  - A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell
      pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged
      hexobarbital-induced sleeping time in mice. The depression of liver drug
      metabolism by a cellular vaccine containing a mutated pertussis toxin was less
      marked than that induced by the wild-type vaccines, indicating that the mutated
      vaccine might have lower toxicity in this regard. The wild-type vaccines
      decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine
      had a less marked effect (a decrease of 30%), paralleling the results obtained in
      sleeping time experiments. Furthermore, an acellular mutated vaccine did not
      affect liver drug metabolism, indicating a role of the whole bacterial cell in
      this side effect. All the cellular vaccines studied induced high serum
      interleukin-6 levels; on the other hand, the acellular mutated vaccine induced
      very low interleukin-6 levels, indicating that the whole bacterial cell is also
      important for interleukin-6 induction. All vaccines studied were very poor tumor
      necrosis factor inducers.

PMID- 8262643
TI  - Effects of cations on Helicobacter pylori urease activity, release, and
      stability.
AB  - The urease of Helicobacter pylori is an important antigen and appears critical
      for colonization and virulence. Several studies have indicated a superficial
      localization for the H. pylori urease, and the purpose of this study was to
      determine the effects of cations on the release and stability of urease activity
      from H. pylori cells. Incubation of partially purified H. pylori urease in water
      containing 1, 5, or 10 mM Ca2+, Mg2+, K+, Na+, EDTA, or EGTA [ethylene glycol
      bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] had little effect on
      activity. In contrast, 1 mM Fe3+, Cu2+, Co2+, or Zn2+ substantially (> 80%)
      inhibited activity, and 10 mM Fe2+, Mn2+, and Ni2+ inhibited about 30% of the
      activity. Addition of Ca2+ or Mg2+ markedly decreased extraction of urease from
      intact H. pylori cells by water, but 1 mM Na+, K+, EGTA, or EDTA each had minimal
      effects on release, suggesting that divalent cations have a role in attachment of
      urease to H. pylori cells. The stability of enzymatic activity at 4 degrees C was
      enhanced by addition of glycerol or 2-mercaptoethanol; however, even after loss
      of activity, full antigenicity for human serum was retained.

PMID- 8262642
TI  - Outer surface proteins E and F of Borrelia burgdorferi, the agent of Lyme
      disease.
AB  - We report the cloning and characterization of two outer surface proteins (Osps),
      designated OspE and OspF, from strain N40 of Borrelia burgdorferi, the
      spirochetal agent of Lyme disease. The ospE and ospF genes are structurally
      arranged in tandem as one transcriptional unit under the control of a common
      promoter. The ospE gene, located at the 5' end of the operon, is 513 nucleotides
      in length and encodes a 171-amino-acid protein with a calculated molecular mass
      of 19.2 kDa. The ospF gene, located 27 bp downstream of the stop codon of the
      ospE gene, consists of 690 nucleotides and encodes a protein of 230 amino acids
      with a calculated molecular mass of 26.1 kDa. Pulsed-field gel electrophoresis
      showed that the ospE and ospF genes are located on a 45-kb plasmid. Comparison of
      the leader sequences of OspE and OspF with those of the four known B. burgdorferi
      Osps (OspA, OspB, OspC, and OspD) reveals a hydrophobic domain and a consensus
      cleavage sequence (L-X-Y-C) recognized by signal peptidase II, and [3H]palmitate
      labeling shows that OspE and OspF are lipoproteins. Immunofluorescence studies
      demonstrated that both the OspE and OspF proteins are surface exposed. These
      features are consistent with the finding that OspE and OspF are B. burgdorferi
      surface lipoproteins.

PMID- 8262644
TI  - Immunogenicity of tetanus toxoid conjugates of anti-idiotypes that mimic
      Pseudomonas aeruginosa surface polysaccharides.
AB  - Pseudomonas aeruginosa continues to be a serious pathogen in humans, and there is
      no commercially available vaccine. We have previously developed monoclonal anti
      idiotypic antibodies that mimic two surface polysaccharide epitopes of
      pseudomonas--the high-molecular-weight polysaccharide of the O side chain of
      immunotype 1 lipopolysaccharide and mucoid exopolysaccharide. We now show that
      conjugation of the anti-idiotypes to the carrier tetanus toxoid is not necessary
      to induce antipolysaccharide antibodies of equal or greater titer than the native
      polysaccharide antigen in mice.

PMID- 8262645
TI  - Inhibition of malaria parasite development in mosquitoes by anti-mosquito-midgut
      antibodies.
AB  - The mosquito midgut plays a central role in the development and subsequent
      transmission of malaria parasites. Using a rodent malaria parasite, Plasmodium
      berghei, and the mosquito vector Anopheles stephensi, we investigated the effect
      of anti-mosquito-midgut antibodies on the development of malaria parasites in the
      mosquito. In agreement with previous studies, we found that mosquitoes that
      ingested antimidgut antibodies along with infectious parasites had significantly
      fewer oocysts than mosquitoes in the control group. We also found that the
      antimidgut antibodies inhibit the development and/or translocation of the
      sporozoites. Together, these observations open an avenue for research toward the
      development of a vector-based malaria parasite transmission-blocking vaccine.

PMID- 8262646
TI  - Construction of a series of congenic mice with recombinant chromosome 1 regions
      surrounding the genetic loci for resistance to intracellular parasites (Ity, Lsh,
      and Bcg), DNA repair responses (Rep-1), and the cytoskeletal protein villin
      (Vil).
AB  - The interval of mouse chromosome 1 extending from Idh-1 to Pep-3 harbors the
      natural resistance gene Ity/Lsh/Bcg; it controls the outcome of infection with
      Salmonella typhimurium, Leishmania donovani, and several Mycobacterium species.
      This region also contains a DNA repair gene, Rep-1, which determines the rapidity
      with which double-strand breaks in chromatin are repaired. BALB/cAnPt and DBA/2N
      mice differ in their phenotypic expression of these genes. To generate
      appropriate strains of mice for the study of these genes, a series of 10 C.D2
      congenic strains recombinant across a 28-centimorgan interval of mouse chromosome
      1 extending from Idh-1 to Pep-3 were derived from crosses of the C.D2-Idh-1 Pep-3
      congenic strain back to BALB/cAn. Analyses of these recombinant strains will
      allow the correlation of biological-immunological phenotypes with defined genetic
      regions.

PMID- 8262647
TI  - An intestinal xenograft model for Cryptosporidium parvum infection.
AB  - Paired segments of near-term fetal rabbit small intestine were transplanted
      subcutaneously into athymic nude mice. At 5 weeks postsurgery, the xenografts
      were inoculated intraluminally with Cryptosporidium parvum sporozoites. Parasites
      rapidly and reliably infected the xenograft mucosal epithelium. Lesions typical
      of cryptosporidiosis were readily apparent by light microscopy and scanning and
      transmission electron microscopy. Xenografts are well suited to the study of the
      early events of C. parvum infection and are of potential value in the evaluation
      of anticryptosporidial chemotherapeutic agents.

PMID- 8262648
TI  - Necessity and sufficiency of beta interferon for nitric oxide production in mouse
      peritoneal macrophages.
AB  - Bacterial lipopolysaccharide and some cytokines can activate macrophages to
      secrete nitric oxide. Macrophage-derived nitric oxide is a key cytotoxic factor
      for microbicidal and tumoricidal processes. We report here that a monoclonal
      antibody specific for beta interferon inhibited lipopolysaccharide-induced nitric
      oxide production in thioglycolate-elicited C3HeB/FeJ peritoneal macrophages and
      macrophage-like cell line RAW 264.7. In addition, exogenous added beta interferon
      enabled lipopolysaccharide-hyporesponsive thioglycolate-elicited C3H/HeJ
      peritoneal macrophages to produce nitric oxide in response to lipopolysaccharide.
      These data support the concept that beta interferon provides an essential
      signal(s) for lipopolysaccharide-triggered nitric oxide production by mouse
      macrophages. Heat-killed Staphylococcus aureus, a gram-positive bacterium which
      was unable to initiate nitric oxide production in thioglycolate-elicited
      C3HeB/FeJ peritoneal macrophages in vitro, promoted nitric oxide formation in the
      presence of beta interferon, suggesting that beta interferon may be a general
      cofactor necessary for bacterium-derived stimulus-induced nitric oxide production
      in these macrophages. However, neither beta interferon nor tumor necrosis factor
      alpha, alone or in combination, triggered nitric oxide production in
      thioglycolate-elicited mouse peritoneal macrophages, demonstrating that these
      macrophage-derived cytokines, while necessary, were not sufficient by themselves
      for the induction of nitric oxide production in these cells. On the other hand,
      gamma interferon and tumor necrosis factor alpha acted together to induce nitric
      oxide production in vitro in the absence of lipopolysaccharide in thioglycolate
      elicited mouse peritoneal macrophages, indicating that these two types of
      interferons provided different signals during the activation of these
      macrophages.

PMID- 8262649
TI  - Identification and characterization of an iron-regulated hemopexin receptor in
      Haemophilus influenzae type b.
AB  - Heme can serve Haemophilus influenzae as a source of both essential porphyrin and
      iron. In extracellular mammalian body fluids neither free heme nor free iron is
      available, since they are tightly bound to hemopexin and transferrin,
      respectively. Since H. influenzae grows in the presence of iron-transferrin and
      heme-hemopexin and is known to express a saturable receptor for transferrin, we
      investigated the process by which this pathogen acquired heme from hemopexin for
      use as an iron source. The ability of human and rabbit hemopexin to donate heme
      as a source of iron to H. influenzae type b strains was demonstrated by plate
      bioassays. With a dot enzyme assay with biotinylated hemopexin as ligand, H.
      influenzae bound heme-hemopexin and apo-hemopexin following growth in iron
      restricted, but not in iron-sufficient, medium. Competitive binding studies with
      heme-hemopexin and apo-hemopexin demonstrated saturability of binding. Neither
      heme, protoporphyrin IX, hemoglobin, nor transferrin blocked the binding of
      hemopexin to whole cells, demonstrating the specificity of binding. Treatment of
      whole H. influenzae cells with trypsin abolished binding. Taken together, these
      observations suggest that H. influenzae type b expresses an outer membrane
      protein(s) which acts as a receptor for hemopexin and which is regulated by the
      availability of iron in the growth medium. In iron-restricted media, H.
      influenzae 706705 and DL42 did not express the 100-kDa hemopexin-binding protein
      previously reported (M.S. Hanson, S.E. Pelzel, J. Latimer, U. Muller-Eberhard,
      and E.J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). The putative
      iron-regulated hemopexin receptor was solubilized from cell envelopes of H.
      influenzae 706705, DL42, and Eagan with the detergent CHAPS (3-[(3
      cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate) and isolated by affinity
      chromatography on heme-hemopexin-Sepharose 4B. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis of the proteins bound to the affinity resin
      revealed three proteins of 29, 38, and 57 kDa, of which the 57- and 29-kDa
      proteins bound hemopexin after Western blotting (immunoblotting). A monoclonal
      antibody to the 57-kDa hemopexin-binding protein of 706705 recognized a 57-kDa
      protein on Western blots of the cell envelope proteins of 706705, DL42, and
      Eagan; no reaction was observed with the 100-kDa hemopexin-binding protein of
      DL42. These data suggest that some H. influenzae strains possess at least two
      hemopexin receptors, the expression of which is determined by the prevailing
      growth environment.

PMID- 8262650
TI  - Evidence that L-(+)-lactate dehydrogenase deficiency is lethal in Streptococcus
      mutans.
AB  - In order to construct an effector strain for the replacement therapy of dental
      caries, we wished to combine the properties of low-level acid production and high
      level colonization potential in a strain of Streptococcus mutans. To this end, we
      made a deletion in the lactate dehydrogenase (LDH) gene cloned from the
      bacteriocin-producing S. mutans strain JH1000. However, we were unable to
      substitute the mutant for the wild-type allele by transformation with linear DNA
      fragments. The mutated gene, carried on a suicide vector, was shown by Southern
      analysis to integrate into the JH1000 chromosome to yield transformants carrying
      both the wild-type gene and mutated LDH gene. Three spontaneous self-recombinants
      of one heterodiploid strain were isolated by screening 1,500 colonies for a loss
      of the tetracycline resistance encoded by the gene used to mark the LDH deletion.
      In all three cases, Southern analysis showed that a loss of tetracycline
      resistance was accompanied by a loss of the mutated LDH gene, resulting in
      restoration of the wild-type genotype. However, screening the same number of
      colonies for self-recombinants that did not make lactic acid during anaerobic
      growth in Todd-Hewitt broth failed to identify clones in which the wild-type
      allele was lost. A second, simpler screening of more than 80,000 colonies grown
      aerobically on glucose tetrazolium medium to identify low-level-acid-producing
      colonies was also unsuccessful. These results are interpreted as indicating that
      LDH deficiency is lethal in S. mutans under the cultivation conditions used in
      these experiments. The physiological bases for this hypothesis are described.

PMID- 8262652
TI  - Isolation, characterization, and cloning of cDNA and the gene for an
      elastinolytic serine proteinase from Aspergillus flavus.
AB  - An elastinolytic serine proteinase produced by Aspergillus flavus 28 that was
      isolated from a patient who died of aspergillosis has been purified and
      characterized. The enzyme was inhibited by the serine proteinase inhibitors
      phenylmethylsulfonyl fluoride and diisopropyl fluorophosphate. The metal
      chelating agents EDTA and EGTA [ethylene glycol-bis(beta-aminoethyl ether)
      N,N,N',N'-tetraacetic acid] did not severely inhibit the enzyme. A cDNA and a
      2.95-kb segment of genomic DNA containing the proteinase gene were sequenced. The
      open reading frame that would code for a protein containing 403 amino acids was
      interrupted by three introns. The mature protein lacks 121 N-terminal amino acids
      including a putative 21-amino-acid signal peptide. The purified mature protein
      showed a molecular mass of 36 kDa by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, whereas that calculated from the deduced protein sequence was 30
      kDa. This elastinolytic serine proteinase of A. flavus has 83 and 82% sequence
      homology to the similar proteinases from A. fumigatus and A. oryzae. The
      catalytic properties and the sequence homology around the putative catalytic
      amino acids suggest that this enzyme belongs to the serine proteinases of the
      subtilisin family.

PMID- 8262651
TI  - Bacterial endosymbiont-derived lipopolysaccharides and a protein on symbiosome
      membranes in newly infected amoebae and their roles in lysosome-symbiosome
      fusion.
AB  - Experimental results are presented to support the view that symbiont-derived
      lipopolysaccharides are involved in the prevention of lysosome-symbiosome fusion
      in xD amoebae harboring bacterial endosymbionts. Monoclonal antibodies against
      lipopolysaccharides and a 96-kDa protein present on symbiosome membranes of
      amoebae were used to monitor the appearance of the membrane-specific components
      in newly infected amoebae with endosymbionts from xD amoebae. The
      lipopolysaccharides and protein appeared on the newly forming symbiosome
      membranes within 3 to 7 days, as detected by indirect immunofluorescence staining
      with monoclonal antibodies. The lysosome-symbiosome fusion was followed by double
      staining of two antigens with different monoclonal antibodies applied to the same
      amoeba. Antilipopolysaccharide monoclonal antibodies were detected by staining
      with a fluorescein isothiocyanate-conjugated secondary antibody, and a
      biotinylated anti-lysosomal protein monoclonal antibody was detected by staining
      with Texas Red-conjugated streptavidin. In xD amoebae injected with an
      antilipopolysaccharide antibody, lysosomes fused with some of the symbiosomes
      that did not fuse with lysosomes in noninjected cells.

PMID- 8262653
TI  - Opposite effects of actively and passively acquired immunity to the carrier on
      responses of human infants to a Haemophilus influenzae type b conjugate vaccine.
AB  - Vaccination of infants with Haemophilus influenzae type b (Hib) capsular
      polysaccharide (HibCP) coupled to carrier proteins has proven protective against
      invasive Hib diseases in several trials. However, insufficient immunogenicity has
      been noted in certain populations. Therefore, studies analyzing factors
      influencing the antibody response to conjugate vaccines are needed. In this
      study, the response to HibCP coupled to tetanus toxoid (TT) was examined in
      relation to (i) priming with or coadministration of the carrier protein and (ii)
      the levels of passively acquired maternal TT antibodies. One hundred forty-four
      infants were vaccinated with HibCP-TT at 5 and 6 months. They were randomized
      into three groups that received TT as part of a diphtheria-tetanus-polio vaccine
      at either 6 and 7 months (group A), 5 and 6 months (group B), or 4 and 5 months
      (group C). Maternally acquired TT antibodies inhibited the anti-HibCP response to
      the first HibCP-TT dose in groups A and B (r = -0.5 and -0.4, respectively; P <
      0.005). In these groups, infants with prevaccination anti-TT levels above the
      median failed to reach the defined long-term protective level of HibCP antibodies
      (1 microgram/ml) more often than infants with low prevaccination levels after the
      first (P = 0.0001) and the second (P = 0.01) doses of HibCP-TT. In contrast,
      active priming with TT at 4 months resulted in a threefold-higher median level of
      anti-HibCP (group C; 1.34 micrograms/ml) than in the unprimed group (group A;
      0.40 microgram/ml) after the first dose of HibCP-TT (P = 0.01). Coadministration
      of TT had no enhancing effect (group B; 0.58 microgram/ml). No significant
      differences between the median anti-HibCP levels were seen after the second HibCP
      TT dose (6.72, 9.63, and 11.44 micrograms/ml in groups A, B, and C, respectively;
      P = 0.25).

PMID- 8262654
TI  - Antigenic variation of parasite-derived antigens on the surface of Babesia bovis
      infected erythrocytes.
AB  - The hemoparasite Babesia bovis antigenically alters the bovine erythrocyte
      membrane surface by expression of isolate-specific, parasite-derived
      polypeptides. To determine whether antigenic variation also occurred on the
      infected erythrocyte surface, a calf was infected once with parasitized
      erythrocytes carrying the C9.1 clonal line of B. bovis. In vitro cultures then
      were established periodically from the peripheral blood and analyzed with
      sequentially collected sera from the same animal. The surface reactivity of
      infected erythrocytes cultured from the infected animal varied over time, on the
      basis of reactivity in live cell immunofluorescence, surface immunoprecipitation,
      and panning assays. Subclones C8 and H10, established from day 41 cultures, were
      analyzed immunochemically. A loss of immunoreactivity was observed in antigens
      corresponding to the 113- and 128-kDa parasite-derived antigens of clone C9.1,
      demonstrating epitopic variation in these antigens; the immunochemical
      recognition of these antigens paralleled the results of live cell
      immunofluorescence and panning assays. Concomitant size polymorphism suggested
      polypeptide structural variation of these antigens as well. Calves infected by
      inoculation of infected blood or by injection of cloned parasites from in vitro
      cultures rapidly developed antibodies which cross-reacted among the clonal
      variant lines, suggesting the presence of common as well as unique epitopes.
      These results demonstrate that antigenic variation occurs on the surface of B.
      bovis-infected erythrocytes and that the parasite-derived antigens of 113 and 128
      kDa compose at least a part of the antigens undergoing variation.

PMID- 8262656
TI  - The human epididymis--is it necessary?

PMID- 8262655
TI  - Similar cytokine but different coagulation responses to lipopolysaccharide
      injection in D-galactosamine-sensitized versus nonsensitized rats.
AB  - To compare cytokine release and coagulation disturbances induced by
      administration of high versus low doses of endotoxin (lipopolysaccharide [LPS]),
      we used two endotoxin test systems similar in mortality but different in the
      degree of endotoxemia. One group of rats (n = 11) randomly received endotoxin
      (15.0 mg/kg of body weight intraperitoneally [i.p.]) and 1 ml of Ringer's
      solution (nonsensitized animals). The second group (n = 11) received 1 ml of D
      galactosamine (500 mg/kg i.p.) and endotoxin (100 micrograms/kg i.p.)
      simultaneously (sensitized animals). Endotoxin levels in the plasma of
      nonsensitized rats were 1,000-fold higher than those in the plasma of sensitized
      rats (69.33 x 10(3) +/- 22.42 x 10(3) versus 75.8 +/- 27.08 ng of LPS per ml),
      leading to a mortality of 91% in nonsensitized rats versus 82% in the sensitized
      rat model within 48 h postendotoxemia. Serum transaminase activity increased up
      to 100-fold in sensitized rats as a sign of hepatocyte damage. Despite the large
      difference in LPS levels in plasma, the time courses of the plasma tumor necrosis
      factor (TNF) increase were similar in the two groups, with a peak at 2 h (54 +/-
      12 ng/ml in nonsensitized rats versus 43 +/- 12 ng/ml in sensitized rats), and
      also similar to that of a group of nonsensitized rats (n = 5) that received a low
      dose of LPS (100 micrograms/kg) only (52 +/- 21 ng/ml), while D-galactosamine
      alone did not induce TNF release. Despite similar TNF levels, a more pronounced
      coagulation disorder was observed at 4 h in nonsensitized rats (with the high LPS
      dose) as measured by platelet counts, plasma fibrinogen levels, and activated
      partial thromboplastin time prolongation (191 x 10(3) +/- 107 x 10(3) cells per
      microliter, 40 +/- 24 mg/dl, and 53 +/- 15 s, respectively) than in rats with the
      low LPS dose either sensitized (495 x 10(3) +/- 153 x 10(3), 95 +/- 49, and 38 +/
      16, respectively) or nonsensitized (439 x 10(3) +/- 62 x 10(3), 170 +/- 18, and
      35 +/- 11, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8262657
TI  - Investigation in real time of the effect of gravitation on human spermatozoa and
      their tendency to swim-up and swim-down.
AB  - To investigate in real time if and how natural gravity affects rates of swim-up
      and swim-down of human spermatozoa, samples of motile or immobilized spermatozoa
      in a sealed mini-chamber were placed vertically on a 90 degrees tilted
      microscope. The mode of their sedimentation, as well as the difference in the
      rate of their swimming up and down, were observed directly over 30 min and
      analysed from photomicrographs. Under the influence of natural gravity force,
      most immobilized spermatozoa turned their heads down in about 5 min and then sank
      slowly at an average speed of 0.2 mu/s. The number of motile spermatozoa that
      swam down was 5-6 times more than those swimming up. It can be implied that in
      spite of the mild force exerted by 1 g on suspended spermatozoa in comparison to
      the high g force obtained by centrifugation, the overall effect of gravity on the
      rate of swimming up or down becomes dominant. Gravity causes the sperm heads to
      turn downward after which the oriented spermatozoa continue to move down by their
      own tail movements, causing accumulation of motile spermatozoa at the bottom.
      This may explain why in some recent studies swim-down was superior to the swim-up
      procedure during sperm separation by self-migration.

PMID- 8262658
TI  - Inverse relationship between the induction of human sperm capacitation and
      spontaneous acrosome reaction by various biological fluids and the superoxide
      scavenging capacity of these fluids.
AB  - Capacitation of spermatozoa is essential for fertilization, and can be induced by
      various agents or biological fluids. Previous reports have shown that foetal cord
      serum (FCS) and the superoxide anion trigger human sperm hyperactivation and
      capacitation, and that superoxide dismutase (SOD) prevents these processes. We
      investigated: (1) the capacity of seminal plasma (SP) and follicular fluid (FF)
      (whole, or fractionated into high and low molecular weight components), in the
      presence or absence of SOD, to induce the spontaneous acrosome reaction (no
      stimulant needed, AR) and capacitation (as measured by the lysophosphatidyl
      choline-induced AR, LPC-AR); (2) a possible relationship between the levels of AR
      and capacitation obtained with these biological fluids and the superoxide
      scavenging capacity of the same fluids. The highest levels of LPC-AR were
      obtained with FF ultrafiltrate (48 +/- 6%), followed by SP ultrafiltrate (31.9 +/
      0.8%), FF (30 +/- 5%), dialysed FF (27 +/- 4%), and finally, by FCS
      ultrafiltrate (23 +/- 1%), SP (21 +/- 1%) and dialysed SP (18.9 +/- 0.8%). A
      similar order of potency for the fluids existed when sperm AR was studied, the
      levels of AR observed ranging from 16 +/- 2% to 5.3 +/- 0.8% after incubation
      with FF ultrafiltrate and SP respectively. None of these treatments had
      detrimental effects on sperm motility. In the presence of SOD, there was always
      an important reduction (52-86%) of the AR and LPC-AR observed.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8262659
TI  - Experimental testicular germ cell tumorigenesis in mouse strains with and without
      spontaneous tumours differs from development of germ cell tumours of the adult
      human testis.
AB  - The aim of this study was to undertake a morphological analysis of the earliest
      stages of experimentally induced (by genital ridge grafting) germ cell tumours in
      mouse strains with (129/Sv-ter) and without (MA) spontaneous tumorigenesis.
      Genital ridges from fetuses aged 12 or 13 days from 129/Sv-ter and MA were
      transplanted into the testes of adult 129/Sv-ter. The results show clearly that
      experimentally induced carcinoma-in-situ in mouse testes differs considerably
      from its human counterpart, found in patients with and without testicular germ
      cell tumours, and considered to be the precursor for all kinds of germ cell
      tumours of the adult testis apart from spermatocytic seminoma. The results
      indicate that development of testicular germ cell tumours is different in man and
      the mouse.

PMID- 8262660
TI  - Intratesticular hormone levels and the route of secretion of hormones from the
      testis of the rat, guinea pig, monkey and human.
AB  - Blood samples were obtained from the testes of rats, guinea pigs and Macaque
      monkeys and from normal men undergoing vasectomy reversal, in order to assess the
      comparative dynamics of hormone secretion. In each species, blood was sampled
      from a vein on the surface of the testis (testicular venous blood, TV), from a
      vein in the spermatic cord above the pampiniform plexus (spermatic venous blood,
      SV) and from a vein elsewhere in the body (peripheral venous blood, PV). Plasma
      concentrations of testosterone and inhibin were then determined by
      radioimmunoassay. In all species, testosterone secretion profiles were
      comparable, with concentrations being greatest in TV blood. SV concentrations
      were reduced by 40-60% compared with TV levels, with a significantly greater
      reduction in PV levels. Inhibin secretion varied significantly between species,
      with the rat being the only animal to show significant increases in inhibin
      concentrations from TV to SV blood. Inhibin secretion in the guinea pig was most
      comparable with that of the rat, although the increased SV levels fell short of
      being significant. Macaque and human profiles contrasted with those of the rat
      and guinea pig, with the greatest inhibin concentrations being found in TV blood.
      Levels in SV blood were reduced by some 40%, and PV levels were reduced
      significantly further. These differences may be due to the different position of
      the rete testis, and its relationship to the testicular vasculature, in these
      species. The sampling procedure described provides a defined set of testicular
      blood samples that could contribute important information of relevance to
      physiological and clinical studies of testicular function.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8262661
TI  - Phenotypic characterization of lymphocytic cell infiltrates into the testes of
      rats undergoing autoimmune orchitis.
AB  - Experimental autoimmune orchitis (EAO) was induced in adult Wistar rats by active
      immunization with a testicular homogenate (TH) and adjuvants. Fifty per cent of
      the immunized rats developed EAO. Testicular damage became evident at 50 days
      after the primary immunization and increased in severity at 80 days. Phenotypic
      characterization of T-cell subsets (CD4+ and CD8+) and Ia+ cells was performed on
      cryostat sections of testis obtained from normal rats, rats immunized with
      adjuvant (control group) and rats immunized with TH and adjuvants (experimental
      group) at 50 and 80 days. Labelled cells were only detected in the interstitial
      area; no labelled cells were observed inside the seminiferous tubules with any of
      the monoclonal antibodies used (W3/25, OX-8, OX-6). A significant increase in the
      numbers of CD4+ and CD8+, as well as of Ia+ cells, were observed in the testis of
      rats with severe EAO at 80 days after the first immunization. Rats of the same
      experimental group without testicular damage showed no major differences compared
      to rats from the control group, with the exception of a lower number of CD8+
      cells. Variations in the lymphocyte subsets in lymph nodes draining the site of
      immunization showed the opposite pattern to that observed in the testis. In
      conclusion, these data suggest the traffic of specifically sensitized lymphocytes
      from lymph nodes to the testis and an active role of CD4+, CD8+ and Ia+ cells in
      the pathogenesis of EAO in the rat.

PMID- 8262662
TI  - In-vitro influence of germ cells on Sertoli cell-secreted proteins: a two
      dimensional gel electrophoresis analysis.
AB  - Two-dimensional polyacrylamide gel electrophoresis (2D PAGE) was used to analyse
      [35S]-methionine-labelled proteins secreted in vitro by Sertoli cells when
      cultured in the presence or absence of enriched preparations of pachytene
      spermatocytes (SPC), early spermatids (SPT) or residual bodies/cytoplasts from
      elongated spermatids (RB/CES). The presence of germ cells modified the pattern of
      Sertoli cell secreted proteins in co-culture. Out of 21 Sertoli cell secreted
      polypeptide families visualized by 2D PAGE, one (referred to as number 12) was
      stimulated, whereas the secretion of polypeptides 1 and 3 was inhibited by all of
      the germ cell populations tested. Early spermatids and RB/CES both enhanced the
      secretion of protein number 10 and inhibited the production of protein 11. The
      RB/CES fraction specifically inhibited secretion of polypeptide 13. Of particular
      note was the finding that co-culture with early spermatids or RB/CES induced the
      secretion of a novel polypeptide, termed GIP (germ cell-induced protein), with an
      apparent molecular weight of 72 kDa and an isoelectric point of 5.9. Under the
      present experimental conditions, media conditioned by the different germ cell
      fractions inhibited the secretion of polypeptide 2 but enhanced the secretion of
      polypeptides 10 and 18; of note also was the finding that media conditioned by
      early spermatids or RB/CES induced the appearance of GIP. This study confirms and
      extends the concept that germ cells influence Sertoli cell function and that the
      effects observed differ according to the stage of development of the germ
      cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262663
TI  - Inhibition of adsorption of human T-cell-leukemia virus type 1 by a plant lectin,
      wheat-germ agglutinin.
AB  - Thirty-six lectins that recognize various sugar chains were examined for
      inhibitory activities against infection with human T-cell leukemia virus type I
      (HTLV-I). Wheat-germ agglutinin (WGA) was the most inhibitory among them: plating
      of the pseudotype of vesicular-stomatitis virus (VSV) bearing envelope antigens
      of HTLV-I was markedly inhibited by treatment of indicator cells with WGA just
      before adsorption, but not by treatment after virus adsorption. Treatment with
      WGA before adsorption, however, could not inhibit the plating of VSV, VSV
      pseudotypes of bovine leukemia virus, Moloney murine leukemia virus and human
      immunodeficiency virus type I. Syncytium formation induced by HTLV-I was also
      inhibited by WGA upon co-cultivation of U-251 MG human glioma cells or MOLT-4
      human T-cells with HTLV-I-producing C91/PL cells. Formation of proviral DNA
      detected one day after infection was also inhibited when indicator cells had been
      treated with WGA before adsorption of HTLV-I, but not after its adsorption. These
      findings indicated that WGA specifically inhibits plating of HTLV-I when added to
      culture just before adsorption and suggested that a substance(s) containing sugar
      chains recognized by WGA might be involved in an adsorption step of HTLV-I.

PMID- 8262664
TI  - Protoporphyrin biosynthesis in melanoma B16 cells stimulated by 5-aminolevulinic
      acid and chemical inducers: characterization of photodynamic inactivation.
AB  - The stimulation of protoporphyrin (PP) biosynthesis in B16 melanoma cells in
      order to facilitate photodynamic cell killing was studied. Biosynthesis and
      accumulation of PP in the melanoma cells was increased from 8 to 15 pmol/mg
      protein by the use of dimethyl-sulfoxide (DMSO), a differentiation-inducer.
      Treatment of the cells with the porphyrogenic agent allylisopropyl-acetamide
      (AIA) stimulated an additional PP increase. The most remarkable enhancement of
      intracellular PP was achieved by the supplementation of 5-aminolevulinic acid (5
      ALA) to the growth medium following the addition of DMSO and AIA during the
      induction phase. The intracellular concentration of PP exceeded 21,950 pmol/mg
      protein following combined stimulation by DMSO/AIA and 5-ALA. The porphyrins
      produced in the incubated cells, in serum-depleted medium, consisted of 95% PP;
      88% of it was recovered from the cells and only 7% was excreted into the medium.
      Photosensitization of the B16 melanoma cells containing high PP concentrations
      was effective even at low light doses. Potassium (K) efflux was the first
      measurable sign of cell damage determined by X-ray microanalysis (XRMA) following
      fast liquid-nitrogen fixation. During a 1 min interval, 70% of cellular K was
      lost. After 5 min illumination, complete cell destruction was detected by
      scanning electron microscopy (SEM) and XRMA. The photodamaged cells showed influx
      of Na, Cl and Ca ions accompanying the immediate K losses. Ultrastructural cell
      damage was manifested by disintegration of the outer membrane. Total cell death
      of B16 melanoma cells was achieved by chemical induction of endogenous PP and
      photosensitization.

PMID- 8262665
TI  - Perinatal and early postnatal risk factors for malignant brain tumours in New
      South Wales children.
AB  - A population-based case-control study of incident primary malignant brain tumours
      diagnosed during 1985-1989 in children aged 0 to 14 years was carried out in the
      coastal conurbation of New South Wales comprising Sydney, Wollongong and
      Newcastle in the period 1988 to 1990. Personal interviews were conducted using a
      structured questionnaire with mothers of 82 cases and 164 control children
      individually matched to the cases by sex and age. Among the hypotheses examined
      were those related to: N-nitroso compounds (sources included diet, dummies,
      medications, tobacco smoke); factors associated with the birth of the child;
      trauma to the head; and irradiation (X-rays and electromagnetic radiation through
      electric blankets or water beds). Reported ever-use of a dummy increased the risk
      of childhood brain tumours (OR = 2.9, 95% CI 1.6 to 5.4), although there did not
      appear to be any consistent indication of rising risk with reported increased
      levels of use. Compared with children who had never used a dummy, categories of
      use during the first year of life of a maximum of "no more than 1 hour per day or
      night", "several hours per day or night", and "most of the day or night" had
      statistically significant odds ratios of 2.6, 3.4, and 2.7 respectively.
      Consumption of fruit by the child before the age of one appeared to be
      protective. No association was found between childhood brain tumours and birth
      weight, being the first-born child, or factors linked with the child's birth;
      head injuries; exposure to X-rays; contact with horses, or living on a farm;
      pesticide treatment of the house during the child's lifetime; or exposure to
      burning incense.

PMID- 8262666
TI  - Dipyridamole modulates multidrug resistance and intracellular as well as nuclear
      levels of doxorubicin in B16 melanoma cells.
AB  - Simultaneous occurrence of resistance to many chemotherapeutic agents, termed
      multidrug resistance (MDR), is a complex phenotype. MDR occurs due to several
      reasons, including over-expression of a 170-kDa membrane-bound protein, called P
      glycoprotein (P-gp), which apparently participates in active drug efflux.
      Multidrug-resistant cells also frequently exhibit an altered pattern of
      intracellular drug distribution, resulting in a reduction in the nuclear level of
      drugs such as doxorubicin (DOX). In this study, the effect of dipyridamole (DP)
      on drug resistance and on intracellular as well as nuclear levels of DOX in
      multidrug-resistant melanoma cells has been examined. For this purpose, drug
      sensitive murine melanoma cells (B16V) and their multidrug-resistant variant
      cells, (B16VDXR; selected for resistance to DOX) which over-produce P-gp, were
      employed. B16VDXR cells were cross-resistant to several anti-cancer agents
      including etoposide (VP-16) and mitoxantrone (Mitox). DP (10 microM)
      significantly potentiated the cytotoxicity of DOX, VP-16 and Mitox towards
      multidrug-resistant B16VDXR cells but not in parental drug-sensitive B16V cells.
      The presence of DP resulted in a 3.7-fold increase in the total cellular level
      and a 4.2-fold increase in the nuclear content of DOX in the resistant cells.
      Isobologram analysis indicates that DP at several pharmacologically relevant
      concentrations synergistically potentiates the activity of DOX in B16VDXR cells.

PMID- 8262667
TI  - Susceptibility to ultraviolet-induced corneal sarcomas is highly heritable in a
      laboratory opossum model.
AB  - The laboratory opossum, Monodelphis domestica, develops hyperplasia and neoplasia
      of the corneal stroma after repeated exposure to low doses of ultraviolet
      radiation (UVR) (non-erythemic in skin). We exposed adult animals from
      genetically diverse families within our colony to determine whether there are any
      heritable components to the risk of this form of eye cancer. From about 5 months
      of age, animals were exposed 3 times a week to a dose of about 125 J/m2 of UVB
      (spectral peak = 302 nm). Thirty-three sibships (151 individuals) completed at
      least 30 weeks of the protocol and 137 individuals completed 45 weeks. For
      genetic analysis, each animal was classified at 30 and 45 weeks as affected with
      corneal sarcoma or not. Heritabilities were estimated for the dichotomous eye
      tumor trait which was highly heritable at both time points. This eye-cancer model
      system is valuable as a source of material for in vitro studies of angiogenesis
      and neoplastic transformation, for in vivo studies of tumor therapy and
      prevention, and for further research on the genetic determinants of cancer.

PMID- 8262668
TI  - Induction and promotion of forestomach tumors by sodium nitrite in combination
      with ascorbic acid or sodium ascorbate in rats with or without N-methyl-N'-nitro
      N-nitrosoguanidine pre-treatment.
AB  - In experiment I, short-term effects of combined treatment with anti-oxidants,
      sodium ascorbate (NaAsA) and sodium nitrite (NaNO2) on forestomach cell
      proliferation were examined in F344 male rats. Groups of 5 animals aged 6 weeks
      were treated for 4 weeks with 0.8% catechol, 0.8% hydroquinone, 1% tert-butyl
      hydroquinone (TBHQ), 2% gallic acid or 2% pyrogallor alone or in combination with
      0.3% NaNO2 in the drinking water and/or 1% NaAsA in the diet. The thicknesses of
      forestomach mucosa in rats treated with anti-oxidants and NaNO2 in combination
      were greater than those with antioxidant alone and additional NaAsA treatment
      further enhanced the thickening of mucosa. It was noteworthy that values for
      mucosae of animals treated with NaNO2 and NaAsA without anti-oxidant were similar
      to those for anti-oxidants. In experiment 2, effects of combined treatment with
      NaAsA or ascorbic acid (AsA) and NaNO2 on carcinogenesis were examined in F344
      male rats with or without N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) pre
      treatment. Groups of 20 or 15 rats, respectively, aged 6 weeks, were given a
      single intra-gastric administration of 150 mg/kg body weight of MNNG in
      DMSO:water = 1:1 or the vehicle alone by stomach tube. Starting 1 week later,
      they received supplements of 1% NaAsA or 1% AsA in the diet and 0.3% NaNO2 in
      drinking water in combination, each of the individual chemicals alone, or basal
      diet until the end of week 52. In MNNG-treated animals, incidences of forestomach
      papillomas and carcinomas were significantly enhanced in the NaNO2 alone group
      (84 and 47%, respectively) as compared with the basal diet group (30 and 10%),
      with further significant increase in carcinomas occurring with additional NaAsA
      (79%, p < 0.05) or AsA (85%, p < 0.05) treatment. In animals without MNNG, all
      animals in the NaNO2 group demonstrated mild hyperplasia, additional
      administration of NaAsA or AsA remarkably enhancing the grade of hyperplasia, and
      resulting in 53% and 20% incidences, respectively, of papillomas. Thus NaNO2 was
      demonstrated to exert promoter action for forestomach carcinogenesis, with NaAsA
      and AsA acting as co-promoters. The results strongly indicate that combined
      treatment with NaAsA or AsA and NaNO2 may induce forestomach carcinomas in the
      long term.

PMID- 8262669
TI  - Receptor-mediated cytotoxicity of alpha-MSH fragments containing melphalan in a
      human melanoma cell line.
AB  - Four alpha-MSH drug conjugates have been synthesized, 2 C-terminal (Pep 3 and 4)
      and 2 central fragments (Pep 1 and 2), the latter being the 4-10 sequence known
      to be the main alpha-MSH-receptor-recognition site. Melphalan was introduced into
      each sequence at different locations. Their ability to recognize alpha-MSH
      receptors as well as their cytotoxic effects were compared in 3 cell lines:
      melanoma, carcinoma and fibroblast cells. Pep 1 and 2 were able to specifically
      bind to MSH receptors on melanoma cells by displacing labelled alpha-MSH from its
      binding sites at concentrations similar to the 4-10 heptapeptide sequence known
      to contain the main receptor-recognition site. They subsequently penetrate the
      cell, most probably by a receptor internalization mechanism, since about half of
      their effect could be inhibited by competition at the receptor level. Significant
      and selective cytotoxic effects to melanoma cells could be observed after only 2
      hr exposure to the drug conjugates. Interestingly, these 2 conjugates, differing
      only in melphalan position, showed completely different cytotoxicity in terms of
      IC50 values, Pep 1 being 24 times more toxic to all cells; but the 2 were equally
      specific to melanoma cells. However, they both were less toxic to all cells than
      melphalan itself. Furthermore, Pep 1 and 2 were able to block the receptor and,
      unlike Pep 3 and 4, their cytotoxic effect could be significantly inhibited by an
      alpha-MSH agonist. Pep 3 and 4 were 5 to 10 times less toxic than melphalan to
      melanoma and carcinoma cells and 50 times less to fibroblast cells, and did not
      show any cell-type selectivity. They were less toxic than Pep 1 to melanoma and
      carcinoma cells by a factor of 2, but equally toxic to fibroblasts. In contrast,
      they were more toxic than Pep 2 to fibroblasts, melanoma and carcinoma by a
      factor of 3, 10 and 24 respectively. Our data strongly suggest a receptor
      mediated cytotoxicity mechanism occurring with alpha-MSH central fragments in
      human melanoma cells due to the presence of alpha-MSH-specific receptors. This
      mechanism appeared to be both peptide- and cell-type-specific.

PMID- 8262670
TI  - Unusually marked hypoxic sensitization to indoloquinone EO9 and mitomycin C in a
      human colon-tumour cell line that lacks DT-diaphorase activity.
AB  - Studies with purified DT-diaphorase have shown that the enzyme is capable of
      catalyzing a two-electron reduction of the novel indoloquinone EO9 to a DNA
      damaging alkylating species. The aim of this study was to determine to what
      extent DT-diaphorase may be involved in the metabolic activation of EO9 and
      mitomycin C in both aerobic and hypoxic conditions. Two human colon-carcinoma
      cell lines were used; HT29 has high levels of DT-diaphorase whilst BE lacks this
      activity because of a point mutation in the NQOI gene. In aerobic conditions the
      2 cell lines show similar sensitivities to a number of cytotoxic drugs including
      cisplatin, doxorubicin and etoposide. They are equally sensitive to the
      benzotriazine di-N-oxide SR 4233 but HT29 is more sensitive than BE to mitomycin
      C and EO9. Sensitivity to SR 4233 is increased by about 100-fold for both cell
      lines in hypoxic conditions. DT-diaphorase-deficient BE cells show markedly
      increased sensitivity to mitomycin C and particularly EO9 in hypoxic conditions,
      whereas DT-diaphorase-rich HT29 cells show little hypoxic sensitization to these
      agents unless exposed in the presence of dicoumarol. These results suggest that
      DT-diaphorase can reduce EO9 and mitomycin C to potent cytotoxic species in
      aerobic conditions, and this activity predominates over the one-electron-reducing
      enzymes even in hypoxic conditions. In the absence of DT-diaphorase activity, EO9
      and mitomycin C are reduced in hypoxic conditions, presumably by one-electron
      reducing enzymes, to a similar or greater extent than is achieved with DT
      diaphorase.

PMID- 8262671
TI  - Aryl hydrocarbon hydroxylase activity in chemically induced and toremifene
      treated mammary tumors in rats.
AB  - Aryl hydrocarbon hydroxylase (AHH) and NADPH-cytochrome P450 reductase (NCR)
      activity of microsomes from liver, lungs, uterus and mammary tumors in
      dimethylbenzanthracene-induced and toremifene-treated female Sprague-Dawley rats
      were studied. AHH and NCR activity in tumors and uteri was low compared with that
      in livers and lungs. The distribution of AHH in tumors was wide and skewed. It
      varied in different tumors of the same animal as widely as between different
      animals. The enzyme activity in tumors did not correlate with that in the liver,
      lungs or uterus of the same animal. Toremifene had no effect on AHH or NCR in
      tumor or liver, but it decreased them in lungs. Tumor AHH activity correlated
      with its overall growth rate and development stage. The results suggest that
      malignant transformation leading to the defect in growth regulation also confuses
      the complex regulatory system of AHH activity.

PMID- 8262672
TI  - Carcinogenicity of 4-methoxyphenol and 4-methylcatechol in F344 rats.
AB  - The carcinogenic potentials of 4-methoxyphenol (4-MP) and 4-methylcatechol (4
      MC), phenolic compounds which are structurally similar to the known forestomach
      carcinogen BHA and the glandular stomach carcinogen catechol respectively, and
      cause considerably enhanced cell proliferation and cytotoxicities in rat
      forestomach and/or glandular stomach epithelium, were examined in male and female
      F344 rats. Groups of 30 male and female animals were administered diets
      containing 2% 4-MP or 2% 4-MC for 104 weeks. Histopathological findings in the 4
      MP case included atypical hyperplasias (male, 67%, female, 37%), papillomas (50%,
      23%) and squamous-cell carcinomas (77%, 20%) in the forestomach. 4-MC induced
      forestomach papillomas (70%, 93%) and squamous-cell carcinomas (53%, 37%), also
      glandular stomach submucosal hyperplasias (90%, 93%), adenomas (100%, 100%) and
      adenocarcinomas (57%, 47%), with ulceration or erosion. The degree of
      differentiation of the squamous-cell carcinomas induced by 4-MP was less than
      with 4-MC. The present study demonstrated unequivocal forestomach carcinogenicity
      for 4-MP and forestomach and glandular stomach carcinogenicity for 4-MC, with
      cytotoxicity and cell proliferation both appearing as important factors for these
      non-genotoxic carcinogens.

PMID- 8262673
TI  - Flow cytometric DNA ploidy defines patients with poor prognosis in node-negative
      breast cancer.
AB  - Flow cytometric DNA analysis was performed on fine-needle aspirates from frozen
      tumour biopsies from 421 node-negative, non-adjuvantly-treated breast-cancer
      patients with a median observation time of 6.75 years. Among premenopausal
      patients (n = 175), those having at least one DNA "hypoploid" subpopulation
      defined as DNA index (DI) < 0.96 or 1.44 < or = 1.92 (n = 81) were characterized
      by early recurrences (log-rank p = 0.05), Wilcoxon p = 0.007), poor overall
      survival (OS) (p < 0.001) and poor survival after recurrence (p < 0.001). In the
      postmenopausal group (n = 246), there were no significant difference among 7
      different DI classes regarding either recurrence-free survival (RFS) or OS. S
      phase fraction (SPF), divided into quartiles, predicted OS in premenopausal
      patients only (p = 0.02). Conventional multivariate Cox analysis of OS in the
      premenopausal group revealed hypoploidy to be the only independent prognostic
      factor involving a relative risk (RR) of 22.8. Age < or = 40 years was of
      marginal significance, whereas SPF, histological grade (WHO), oestrogen and
      progesterone receptor (PgR) content, tumour size and number of lymph nodes
      removed were excluded from the model. Application of the conventional Cox model
      to the premenopausal group regarding RFS was found inappropriate due to lack of
      proportionality of the hazards of hypoploidy due to lack of proportionately of
      the hazards of hypoploidy, SPF and histological grade. However, introduction of
      time-dependent co-variates using 2 years as cut-off level showed hypoploidy with
      a RR of 3.52 and age < or = 40 years with a RR of 3.28 to be independent
      prognostic factors. In the postmenopausal group, the conventional Cox model
      identified the number of lymph nodes removed to be the only independent
      prognostic factor regarding RFS as well as OS, whereas SPF < 9% (lowest quartile)
      was of marginal significance in RFS analysis. Hypoploidy was correlated to high
      SPF, low PgR content and low differentiation, indicating that hypoploid tumours
      proliferate rapidly and hormone-independently. These patients may therefore
      benefit from adjuvant chemotherapy administered while tumour burden and risk of
      drug resistance are still low.

PMID- 8262674
TI  - Significance of epidermal growth factor receptor expression in primary human
      endometrial cancer.
AB  - Radioreceptorial assessment of EGFR expression was prospectively performed on 60
      primary human endometrial tumors. Of these, 26 were EGFR-positive while 13
      expressed high EGFR levels. High EGFR levels correlated well with poor
      histopathological grading. No correlation with histopathological type, stage,
      myometrial invasion, lymph-node involvement or steroid hormone receptor status
      was observed. Disease-free survival rate was significantly shorter in the cases
      with high than in the cases with low EGFR levels. These results suggest a
      potential role of EGFR expression assessment in prognostic characterization of
      endometrial cancer patients.

PMID- 8262675
TI  - Trends in cancer mortality in the USSR, 1965-1990.
AB  - Trends in age-specific and age-standardized mortality from 10 major cancer sites
      and total cancer mortality in the USSR were analyzed for the period 1965-1990, on
      the basis of the World Health Organization mortality database. Gastric cancer
      mortality declined substantially. Still, these rates were among the highest
      registered in the world, and in 1990 stomach cancer accounted for over 85,000
      deaths, being the second cause of cancer death (and the first one until 1980);
      further, there was some indication of a levelling of the declines in gastric
      cancer rates for both sexes over most recent calendar years. Likewise, uterine
      cancer mortality declined between 1965 and 1985, but there was no further decline
      over the last 5 years. Upward trends were registered for cancers of the
      intestine, of the breast and of the prostate. Mortality from these neoplasms,
      however, was still comparatively low by worldwide standards. Leukaemia rates were
      stable in both sexes. Substantial rises were observed for cancers of the oral
      cavity and pharynx, larynx and, chiefly, lung. Even more unfavourable was lung
      cancer mortality in young and middle-aged males, since the truncated rate of
      121/100,000 in 1990 was higher than the values reached by countries like England
      and Wales or Finland even at the top of their epidemic in the 1960s, and trends
      in the USSR were still upwards. Thus, total cancer mortality was 176/100,000
      males in 1965, declined to 170 in 1970, but increased thereafter, particularly
      over the last decade, to reach 203/100,000, i.e., one of the highest rates on a
      worldwide scale. Among females, the overall cancer mortality rate declined
      between 1965 and 1975, but rose thereafter to a value intermediate on a worldwide
      scale. These recent unfavourable trends of cancer mortality in the USSR indicate
      that, in the absence of adequate intervention, particularly on the tobacco
      related cancer epidemic, overall cancer mortality will continue to rise in the
      foreseeable future.

PMID- 8262676
TI  - Expression of type-IV collagenases in human tumor cell lines that can form liver
      colonies in chick embryos.
AB  - Chick embryo has been used as a model system for evaluating the metastatic
      potential of tumor cells. We have previously demonstrated that expression of the
      tissue inhibitor of matrix metalloproteinase-I (TIMP-I) gene can suppress liver
      colonization of tumor cels in chick embryo, probably by inhibiting the activity
      of matrix metalloproteinases (MMP) produced by tumor cells. In an attempt to
      identify MMP associated with liver colonization, we examined 24 human tumor cell
      lines for their potential to form metastatic colonies in chick-embryo liver after
      the cells had been inoculated into the chorioallantoic membrane (CAM) vein. We
      compared the results with the mRNA expression of MMP (MMP-I, MMP-2, MMP-3, MMP-9)
      studied previously. Three of 8 cell lines from mesenchymal tumors (fibrosarcoma
      HT1080, osteosarcomas SK-ES and MNNG/HOS) and 2 of 16 cell lines from epithelial
      tumors (gastric carcinoma KKLS and bladder carcinoma T24) proliferated in the
      livers. MMP-2 and MMP-9 were the enzymes whose transcripts were more frequently
      expressed in these 5 metastatic cell lines (MMP-1; 2/5, MMP-2; 4/5, MMP-3; 0/5,
      MMP-9; 3/5), but other cell lines that did not form liver colonies expressed the
      transcripts at lower frequency (MMP-2; 7/19, MMP-9; 3/19). Although either or
      both MMP-2 and MMP-9 transcripts were expressed in 4 of the 5 metastatic cell
      lines, they were undetectable in T24 cells. However, induced expression of both
      enzymes was detected by immunostaining in the T24 cells colonized in the liver.
      Thus, type-IV collagenases expressed by tumor cells may play a role in
      facilitating colonization in chick embryos.

PMID- 8262677
TI  - High prevalence of neutralizing activity to Helicobacter pylori cytotoxin in
      serum of gastric-carcinoma patients.
AB  - Helicobacter pylori infection is causally related to chronic type-B gastritis,
      and may also be associated with an increased risk of gastric carcinoma.
      Vacuolating cytotoxin, which is an 87-kDa protein secreted by H. pylori, induces
      eukaryotic cell vacuolation in vitro. To determine whether there is an
      association between H. pylori vacuolating cytotoxin and gastric carcinoma, we
      investigated several characteristics of H. pylori infection, i.e., isolation of
      H. pylori from gastric biopsies, antibodies specific for H. pylori, detection of
      neutralizing activity to vacuolating cytotoxin in serum and immunological
      detection of cytotoxin by serum. Out of 6 sera from gastric-carcinoma patients,
      all showed the neutralizing activity to vacuolating cytotoxin, in contrast to 3
      of 5 sera from peptic-ulcer patients. Normal individuals showed no neutralizing
      activity. All sera possessing the neutralizing activity recognized an 87-kDa
      protein band by Western blot analysis. Our results confirmed that cytotoxin
      neutralizing activity in human sera was associated with immunodetection of an 87
      kDa protein. To further evaluate neutralizing activity in serum from gastric
      carcinoma patients, we retrospectively analyzed frozen-stocked serum samples from
      22 gastric-carcinoma patients. Sera from 21 of these 22 patients exhibited
      neutralizing activity. These sera were also checked for antibodies to H. pylori,
      using an ELISA; 16 sera showed positive results. Our results indicate that
      detection of cytotoxin-neutralizing activity in sera is strongly associated with
      H. pylori infection, and probably with gastric carcinoma, and is also of interest
      in the diagnosis of H. pylori infection.

PMID- 8262678
TI  - Antenatal risk factors for malignant brain tumours in New South Wales children.
AB  - A population-based case-control study of incident primary malignant brain tumours
      diagnosed during 1985 to 1989 in children aged 0 to 14 years was carried out in
      the coastal conurbation of New South Wales comprising Sydney, Wollongong and
      Newcastle in the period 1988 to 1990. Personal interviews were conducted using a
      structured questionnaire with mothers of 82 cases and 164 control children
      individually matched to the cases by sex and age. Among the hypotheses being
      examined were those related to exposure to parental tobacco smoke, N-nitroso
      compounds and possible protection from sources of vitamin C. No link was found
      with tobacco smoking by the mother before or during pregnancy. While exposure
      during pregnancy of the mother to tobacco smoke of the father appeared to double
      the risk of childhood brain tumours and a similar risk was found for father (but
      not mother) smoking before the index pregnancy, there was no "dose-response" and
      the increased risk was confined to data supplied by the mother (rather than the
      father himself). The risk of childhood brain tumours rose with reported
      increasing consumption, during pregnancy, of cured meats, which have high levels
      of N-nitroso compounds (or their precursors), and fell with rising consumption of
      vegetables. No association was found between the risk of childhood brain tumours
      and family history of epilepsy, cancer, or tumours of the nervous system,
      parental irradiation, previous miscarriage or procedures carried out during
      pregnancy, maternal consumption of antihistamines, barbiturates or diuretics, or
      maternal contact with cats or farm-life during pregnancy.

PMID- 8262679
TI  - The relative prognostic significance of total cathepsin D and HER-2/neu oncogene
      amplification in breast cancer. The South Australian Breast Cancer Study Group.
AB  - Total tumor cathepsin D (TCD) levels were determined prospectively by a
      radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients
      diagnosed between 1989-1991. In 581 of these patients, tumor HER-2/neu oncogene
      amplification was simultaneously determined. In a "training-set" of 313 patients,
      "high" TCD was associated with significantly shorter disease-free survival (DFS).
      For the whole group, there was no correlation between TCD and pathologic stage,
      number of axillary nodes with tumor deposits, tumor size, histologic type and
      grade, or hormone receptor levels. In the node-positive group, high TCD level was
      associated with HER-2/neu amplification. After a median follow-up duration of 31
      months, univariate analysis indicated that high TCD level was significantly
      associated with shorter DFS only in node-positive patients. The shorter DFS in
      association with high TCD levels was observed in both estrogen-receptor-positive
      and -negative patients. Cox multivariate analysis of DFS confirmed that high TCD
      level was predictive of shorter DFS in node-positive patients only. Because of
      the short duration of follow-up, the significance of TCD in overall survival was
      not determined. We conclude that high tumor TCD in node-positive patients is
      predictive of shorter DFS, and is often associated with HER-2/neu amplification.
      The possibility exists that high tumor TCD may act in combination with HER-2/neu
      amplification to promote dissemination of metastases.

PMID- 8262680
TI  - Risk factors for renal-cell carcinoma in Denmark. III. Role of weight, physical
      activity and reproductive factors.
AB  - A population-based case-control study of risk factors for renal-cell carcinoma
      was conducted in Denmark from 1989 to 1992. A total of 368 histologically
      verified cases and 396 controls were included. Information on weight, height,
      physical activity and reproductive factors were collected in a structured
      interview, along with information on other suspected risk factors. A significant
      increase in risk was seen for obese women but not obese men. Although there was
      no clear gradient, the risk was highest among women with a relative weight in the
      upper 5% (OR 6.1; 95% CI, 2.3 to 16.1). The increased risk was most evident for
      high relative weight in ages 30 to 50. No association was observed for height or
      physical activity. Use of amphetamines was associated with increased risk but,
      because of the close link with obesity, we were unable to provide evidence that
      amphetamines are an independent risk factor. We found some evidence for an
      association with reproductive variables, including decreased risk for women with
      late menarche and first pregnancy and birth. We observed no association with
      number of pregnancies or age at menopause, or use of estrogen-containing
      medication.

PMID- 8262681
TI  - Amplification of the epidermal-growth-factor-receptor gene correlates with
      different growth behaviour in human glioblastoma.
AB  - The objective of our study was to determine the frequency of EGF-receptor-gene
      rearrangement in relation to tumour-growth behaviour in an unselected group of
      glioma patients. We investigated 73 glial tumours with different grades of
      malignancy (17 low-grade gliomas, 14 anaplastic variants, and 42 GBM) by Southern
      analysis, reverse transcriptase PCR (RT-PCR) amplification of mRNA, and Western
      analysis. An amplification of the EGF-receptor gene was present in 19/42 GBM but
      in only 1 anaplastic astrocytoma. By RT-PCR, 4/19 GBM with gene amplification
      showed a specific amino-terminal aberrant splice mutation of 801 bp in addition
      to undeleted mRNA. By Western analysis, 27/42 GBM showed expression of the EGF
      receptor protein. Protein levels, however, varied among individual tumours. Four
      GBM containing an aberrant splice mutation exhibited an immunoreactive protein of
      130 kDa MW in addition to the normal EGF-receptor protein p170. All GBM patients
      underwent surgery followed by a standard course of radiotherapy.
      Neuroradiological follow-up in 31/42 GBM patients consisted of bimonthly MRI
      examinations. There was a statistically significant difference in the mean
      latency period until tumour regrowth of patients suffering from GBM with and
      without EGF-receptor-gene amplification (9 weeks vs. 32 weeks). Our data indicate
      more rapid tumour regrowth kinetics of GBM with amplified EGF receptor genes in
      vivo.

PMID- 8262682
TI  - Preferential usage of T-cell receptor alpha beta variable regions among tumor
      infiltrating lymphocytes in primary human malignant melanomas.
AB  - The usage of T-cell-receptor (TCR) alpha beta variable (V) regions among tumor
      infiltrating lymphocytes (TILs) in primary human malignant melanomas was
      characterized using a method based on the polymerase chain reaction (PCR). A
      panel of 57 different variable-region primers specific for the TCR V alpha I-29
      and V beta I-28 was designed, and a semi-quantitative PCR method applicable to
      formalin-fixed, paraffin-embedded tissues was developed. This semi-quantitative
      method was demonstrated to be reproducible and to be useful for the assessment of
      V alpha- and V beta-gene-family usage in formalin-fixed, paraffin-embedded tissue
      samples. A total of 9 different histopathologically characterized primary tumors
      were analyzed in this study. The TILs in these tumors were found to
      preferentially express certain TCR V alpha and V beta regions. The differential
      usage of certain V alpha regions was very pronounced as illustrated by V alpha 4,
      which was highly expressed in 3/8 tumors, and V alpha 22, which was highly
      expressed in 4/8 tumors. For comparison, specific highly expressed V alpha
      regions in control samples of peripheral-blood lymphocytes rarely exceeded 10%.
      The most highly expressed V beta region was V beta 8, which was highly expressed
      in 2/8 tumors. For the highly expressed V alpha 4 and V alpha 22 and V beta 8
      regions, the high levels may be explained by the in situ clonal or oligoclonal
      expansion of TIL. In one specific case, the high expression of V beta 8 was due
      to expansion of a single clone of TILs, as evidenced by a fully readable sequence
      of the CDR3 (V-D-J) region, determined by direct sequencing of the PCR product
      corresponding to V beta 8. In contrast, sequence analysis of V alpha 22, which
      was expressed in the same tumor sample at similar levels, demonstrated the
      simultaneous presence of 3 different CDR3 (V-J) sequences derived from V alpha 22
      transcripts of exactly the same length. The observed preferential use of TCR V
      alpha and V beta regions suggests the in situ clonal expansion of specific
      populations of T-cells, possibly reactive with melanoma-associated peptides
      presented by HLA molecules. The preferential use of TCR V alpha and V beta
      regions may imply the involvement of a limited number of shared melanoma
      associated peptides.

PMID- 8262683
TI  - Altered homologous and heterologous gap-junctional intercellular communication in
      primary human liver tumors associated with aberrant protein localization but not
      gene mutation of connexin 32.
AB  - Gap-junctional intercellular communication (GJIC) in 20 primary human liver
      tumors with different degrees of malignancy has been studied at the functional
      and molecular levels. When GJIC capacity was determined by dye-transfer assay
      performed directly with freshly removed tumor tissue, significant reduction was
      found in all samples, regardless of their morphology. In addition, a selective
      lack of GJIC between tumor and surrounding non-tumorous cells was observed in
      some cases, probably due to the physical separation between them resulting from
      encapsulation of tumors. There was, however, no essential change in the level of
      expression of the major liver gap-junction protein, connexin (cx) 32, in liver
      tumors as measured by Northern and Western blot analyses. Immunohistochemical
      study revealed aberrant localization of cx 32 in the majority of malignant liver
      tumors. Instead of cytoplasmic membrane localization at intercellular contacts,
      cx 32 was detected mainly either intracytoplasmically or in plasma membrane free
      from contact with other cells. We did not detect any mutation in the coding
      sequence of the cx 32 gene from any of the human liver tumors we tested. Thus it
      is likely that the aberrant localization of cx 32 in tumor cells is due to
      disruption of the mechanisms for establishment of this protein into gap-junction
      plaques, rather than to structural abnormality of the cx 32 protein itself.
      Another member of the connexin family, cx 43, not detectable in non-tumorigenic
      hepatocytes, was expressed in several tumors, especially in invasive areas, but
      was detected in only a few tumor cells and was localized intracytoplasmically,
      suggesting that cx 43 protein is not involved in GJIC in the tumors.

PMID- 8262684
TI  - Concentration/effect analysis of verapamil: evaluation of different approaches.
AB  - Plasma concentration and PR-interval prolongation were correlated after a single
      dose of 80 mg verapamil (trial A) and at steady-state during one dose interval
      (80 mg verapamil t.i.d.) on day 7 (trial B) and day 14 (trial C) and the
      subsequent dose interval at the afternoon on day 14 (trial D). The
      pharmacokinetic parameters of verapamil indicated a two-fold increase in AUC and
      Cmax at trial B and C when compared with the single dose application, but AUC and
      Cmax were considerably lesser during the afternoon dosing interval (trial D). For
      each subject, concentration/effect analysis was established: according to a
      linear and a sigmoidal model, and using a plasma concentration vs effect approach
      (1) and a semiparametric effect-site concentration vs effect approach (2). The
      comparison of the two different approaches and models showed that in general, the
      concentration/effect analysis based on the linear model and with approach 2 gave
      the best description of the dromotropic response to verapamil for the majority of
      the individuals. However, approach 1 accounts for 30 to 50% of the
      concentration/effect curve established in the data subsets of trial A to D, and
      about 40% of all curves in trial A, B and C can be more precisely described with
      the Emax-model, whereas almost all curves obtained in trial D were best described
      by a linear model. A decrease in the responsiveness to verapamil at steady-state
      was indicated by both models, but more precisely described by the parameters of
      the Emax-model.

PMID- 8262685
TI  - Transdermal nicotine in smoking cessation and involvement of non-specific
      influences.
AB  - The efficacy of a nicotine transdermal therapeutic system (TTS) (available size
      10, 20 and 30 cm2; nicotine delivery rate = 0.7 mg/cm2/24 h) as an aid for
      smoking cessation, was evaluated in a randomized, single-blind, placebo
      controlled, monocenter study using 160 heavy-smokers (> 20 cigarettes/day), male
      and female, who were divided into two matched parallel groups. The nicotine
      replacement treatment lasted for 3 months and was carried out according to the
      manufacturers recommendations. Abstinence was defined as smoking no cigarette
      during the last week of each month and COHb-levels < or = 1.2%. Efficacy was
      assessed using abstinence rates, withdrawal symptoms and cigarette consumption.
      Although at the commencement of the study all subjects expressed a high
      motivation to stop smoking, about a third were lost to follow-up at 4 weeks. This
      was attributed mainly to the lack of counselling and group dynamics. The greatest
      effect on smoking cessation and cigarette consumption was attributable to a non
      specific aspect of treatment, i.e. the motivation to stop smoking on application
      of the first patch. On an intention-to-treat basis (all subjects), abstinence
      rates were 24% and 18% after 1 month, 24% and 14% after 2 months and 14% and 6%
      after 3 months for the nicotine-TTS and placebo-TTS, respectively. Nicotine-TTS
      was at least twice as effective as placebo in maintaining nicotine abstinence.
      The superiority of the nicotine-TTS was supported by the trend to a higher
      craving-for-cigarettes score and significantly higher blood COHb and cigarette
      consumption in the non-abstainers treated with placebo.

PMID- 8262686
TI  - Modern approach to the evaluation of combined effects of single-dose trials and
      clinical time-course studies, exemplified by combinations of pirenzepine and H2
      receptor antagonists.
AB  - A modern approach to the evaluation of combined effects of two active drugs, A
      and B, in clinical trials is described, based on modern understanding of actions
      and interactions of drugs which act at distinct molecular sites. It rests on a
      comparison of observed combined effects with calculated effects of independent
      action of A plus B--greater than independent effects are considered as a
      potentiated response. It is illustrated by reanalysis of single-dose and time
      course studies of the antisecretory action of pirenzepine and H2-receptor
      antagonists (cimetidine, ranitidine). Briefly, peptone-stimulated acid output was
      measured in 15 min periods over 3 h after the injection of drugs in three trials,
      one with five duodenal ulcer patients, two of them with 8 healthy volunteers
      each. The doses of pirenzepine and H2-blockers were fixed in each trial. The
      results were either expressed by the total acid output (single-dose analysis) or
      by the acid secretion over 15 min as time course. The results with the drug
      combination show greater reduction in acid secretion in all three trials with
      respect to independent effects. The time-course studies more clearly showed
      greater reduction in acid output than the analysis of total acid output, not the
      least with respect to p-values of differences between observed combined effects
      and calculated independent effects. They were obtained by the chi-square (chi 2)
      goodness-of-fit test, recently applied for the evaluation of dose-response
      curves.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262687
TI  - Cocaine: friend or foe? (Part 2).
AB  - The cocaine epidemic is growing at an alarming rate in the United States. Medical
      and social implications of cocaine abuse are many and include such aspects as
      intoxication, personal, financial and moral ruin. Complications associated with
      cocaine use more commonly involve the cardiovascular, central nervous system and
      the reproductive systems. One of the major concerns regarding cocaine abuse goes
      far beyond its ill effects on the user. High incidence of congenital
      malformations and the learning and behavioral disorders in the infants results in
      a growing number of "misfit" or "undesirable" citizens in the country. Hence, the
      healthcare providers, the politicians and the legal system must intensely direct
      their efforts at eradicating this menace.

PMID- 8262688
TI  - Treatment of glucose intolerance in pregnancy: staged diabetes management.
AB  - Current methods for the treatment of glucose intolerance first discovered in
      pregnancy are reviewed and a systematic data-based approach is introduced.
      Gestational diabetes mellitus (GDM) is a leading cause of adverse perinatal
      outcome in 5% of all pregnancies in the United States. Early detection and
      initiation of treatment meant to restore euglycemia will prevent many of the
      major complications associated with hyperglycemia. Staged Diabetes Management
      (SDM) is introduced in this paper as an innovative approach for the detection and
      treatment of GDM and glucose intolerance in pregnancy. Relying on self-monitored
      blood glucose data, SDM guides the primary care physician through increasingly
      more complex regimens until euglycemia is reached. Computer-based technologies
      assist the clinical decision-making by producing Ambulatory Glucose Profiles
      (AGP), which are graphic representations of glycemic control. SDM combined with
      AGP technology are meant to significantly reduce the threefold greater risk of
      adverse outcome in pregnancy experienced by women with GDM.

PMID- 8262689
TI  - Double-blind placebo-controlled ultrasonographic confirmation of constriction of
      the common bile duct by morphine.
AB  - Although the increase in the common bile duct pressure in response to morphine
      has been repeatedly reported in experimental animals and humans, this is the
      first double-blind non-invasive, ultrasonographic study designed to demonstrate
      constriction of the common bile duct caused by i.v. administration of morphine in
      surgical patients. In a double-blind, placebo-controlled, randomized study, 12
      patients undergoing open cholecystectomy were enrolled. No opioids were allowed
      for 12 hours prior to the study. After premedication with midazolam and
      glycopyrrolate, anesthesia was induced by midazolam, 50 micrograms/kg-1 and
      thiopental, 3.0-5.0 mg/kg-1. Tracheal intubation was facilitated by
      succinylcholine, 1.0 mg/kg-1 and muscle relaxation was maintained with
      vecuronium. Anesthesia was maintained with enflurane and nitrous oxide in oxygen.
      After imaging the common bile duct by ultrasonography, placebo or morphine, 0.2
      mg/kg-1 was injected intravenously. The diameter of the common bile duct was
      measured before and 4 and 8 minutes after the drug. Student t-test was utilized
      for statistical analysis. P < 0.05 was considered significant. No significant
      change in common bile duct diameter was observed after placebo administration.
      Morphine caused a significant reduction in the diameter of the common bile duct.
      Before morphine, the mean +/- SD diameter was 9.5 +/- 3.3 mm; after morphine at 4
      and 8 minutes, 7.2 +/- 2.1 and 5.8 +/- 2.1 mm, respectively. It is concluded that
      ultrasonography in a double-blind placebo-controlled design has proven to be a
      valid method for the evaluation of the effect of drugs on the common bile
      duct.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262690
TI  - Comparison of the bronchodilator efficacy of nebulized pirenzepine and
      ipratropium bromide in patients with airway obstructive lung disease.
AB  - Ipratropium bromide (IB) is a non-selective muscarinic antagonist, whose
      bronchodilator efficacy has been shown in reversible and irreversible obstructive
      airway diseases. Pirenzepine is a M1 receptor antagonist and effective in vagally
      induced bronchoconstriction. To investigate the bronchodilator efficacy of
      nebulized pirenzepine, we compared nebulized pirenzepine with nebulized IB and
      nebulized isotonic saline (placebo). Eighteen patients with reversible and 18
      patients with irreversible obstructive airway disease were studied. Nebulized
      isotonic saline (placebo), 100 mcg nebulized pirenzepine and 125 mcg nebulized IB
      were given on three consecutive days. Spirometry was performed prior to
      nebulization and repeated at 5, 30, 60, 90 and 120 minutes following nebulized
      medication. A dose of 125 mcg IB resulted in a significant increase in FEV1 in
      patients with both reversible or irreversible bronchoconstriction (p < 0.00001, p
      < 0.03). IB at the same dose resulted in an increase in FVC in patients with
      irreversible bronchoconstriction (p < 0.001) and an increase in FEF25-75 in
      patients with reversible bronchoconstriction (p < 0.0003). Pirenzepine therapy
      resulted in no significant change in the same parameters. It is concluded that
      nebulized pirenzepine at a dose of 100 mcg does not have bronchodilator effect in
      patients with reversible or irreversible bronchoconstriction.

PMID- 8262691
TI  - TopFit: a PC-based pharmacokinetic/pharmacodynamic data analysis program.
AB  - The program TopFit was developed and validated within the European pharmaceutical
      industry. It provides both pharmacokinetic data analysis support for
      international regulatory submissions of new drugs, and sophisticated techniques
      for model-based kinetic/dynamic evaluation during drug development. TopFit
      features are: (1) non-compartmental methods; (2) standard compartment models
      assembled from input and disposition modules; (3) a potentially unlimited number
      of linear user-defined models that accommodate metabolites, effects, and
      absorption profiles; (4) a library of 24 non-linear models. No user programming
      is required. A well-defined file structure allows ready exchange of data with
      other programs such as SAS. TopFit version 2.0 is now commercially available,
      with comprehensive documentation, in the form of an MS-DOS application for the
      PC.

PMID- 8262692
TI  - Acceleration of natural killer (NK) cell recovery by a glucan, sizofiran, in anti
      asialoGM1 antibody-treated mice.
AB  - The proportion of asialoGM1 positive cells and NK activity of murine splenic
      cells was reduced to almost zero one day after intravenous injection of rabbit
      anti-asialoGM1 antibody. The cells and the activity started to increase at the
      latest 3 days after the injection, although the proportion was far below that of
      the normal control. The proportion of asialoGM1 positive cells and NK activity
      increased more remarkably when 1,3-beta glucan, sizofiran, was administered
      intramuscularly one day after the antibody injection. The increases were dose
      related (50-1000 micrograms/mouse). The fact that sizofiran hastened the
      recoveries of splenic NK activity and asialoGM1 positive cells suggests sizofiran
      may have the activity to accelerate the differentiation of asialoGM1 positive NK
      cells.

PMID- 8262693
TI  - The effect of ebselen on polymorphonuclear leukocyte migration to joints in rats
      with adjuvant arthritis.
AB  - We have previously reported that ebselen (PZ 51,2-Phenyl-1,2- Benzoisoselenazol-3
      (2H)-one), a selinyl organic compound with anti-inflammatory properties,
      inhibited human polymorphonuclear leukocyte (PMNL) adhesion to and migration
      through cytokine-activated human umbilical vein endothelium in vitro. Here we
      investigated the in vivo effect of ebselen on PMNL migration into arthritic
      joints and dermal inflammation in rats with adjuvant arthritis. The rats were
      immunized with adjuvant (Mycobacteriaum butyricum in mineral oil) and 13 days
      later, when arthritis was fully developed, treatment (p.o.) with ebselen,
      indomethacin or vehicle was initiated. The migration of 51Cr-labelled blood PMNL
      purified from arthritic donors and extravasation of 125I-labelled HSA in
      arthritic joints and dermal inflammatory reactions was quantitatively measured.
      Treatment of rats with 100 mg/kg/day ebselen for 3 days, inhibited by 72-79% the
      PMNL migration into arthritic joints and tail (spondylitis) and by 50-60% into
      dermal inflammatory reactions induced with zymosan-activated rat serum (ZAS;
      C5adesArg), endotoxin (LPS) or IL-1 alpha. The inhibitory effect of ebselen was
      dose-dependent, because treatment of rats with 100 mg/kg/day ebselen caused
      significantly more inhibition of PMNL migration than did 30 mg/kg/day, although
      this dose was still effective. Ebselen inhibited PMNL migration into arthritic
      joints and dermal inflammation within 3 h of initial oral administration (100
      mg/kg). However, ebselen did not suppress plasma albumin extravasation into
      arthritic joints and dermal inflammatory reactions. Compared to ebselen,
      treatment with indomethacin (2 mg/kg/day) was significantly less effective in
      inhibiting PMNL accumulation in joints, but in contrast to ebselen, indomethacin
      did inhibit plasma albumin extravasation into carpal and talar joints. The
      results suggest that ebselen effectively and rapidly inhibits PMNL migration in
      vivo, as also observed in vitro, and that it has anti-inflammatory actions
      distinct from classic nonsteroidal anti-inflammatory drugs such as indomethacin.

PMID- 8262694
TI  - 2-Buten-4-olide (2-B4O) inhibits type II collagen-induced arthritis in Lewis
      rats.
AB  - 2-Buten-4-olide (2-B4O) is an endogenous substance which suppresses appetite
      and/or food intake. We studied its effect on type II collagen-induced arthritis
      (CIA) in Lewis rats, an animal model for human rheumatoid arthritis. Bovine type
      II collagen with incomplete Freund's adjuvant was injected intradermally into
      Lewis rats to induce CIA. 2-B4O (50 or 100 mg/kg) significantly inhibited the
      expression of the clinical symptoms when administered i.p. daily from day 1 to 21
      after immunization. Furthermore, administration of 2-B4O daily from day 15 to 21
      significantly reduced the severity of symptoms in established CIA. In addition,
      the progression of soft tissue swelling and articular bone erosions were
      suppressed by daily administration of 2-B4O. 2-B4O also significantly suppressed
      the delayed-type hypersensitivity (DTH) response to type II collagen at doses of
      50 and 100 mg/kg. Finally 2-B4O significantly inhibited the formation of anti
      type II collagen antibody at a dose of 100 mg/kg, but not at 50 mg/kg. These
      results suggest that 2-B4O has the strong inhibitory effects and therapeutic
      usefulness effects on CIA through the suppression of immune responses to type II
      collagen.

PMID- 8262695
TI  - Cytometric profiles of bone marrow and spleen lymphoid cells after mercury
      exposure in mice.
AB  - The potential immunotoxic effects of mercury chloride on murine bone marrow (bm)
      cell subpopulations, including analysis of maturation patterns for B-cells, were
      evaluated by flow cytometric analysis. CD-1 outbred mice were exposed for 28 days
      to relatively low doses of 25-100 ppm HgCl2 in drinking water and the mercury
      related functional cellular changes were validated in a macrophage phagocytosis
      assay. Lymphocyte subsets from the bone marrow population were stained with PNA
      lectin and a panel of monoclonal antibodies against cell surface antigens. The
      incidence of subset-specific staining was also monitored in spleens and thymuses.
      A dose-effect correlation was noted for the mercury-related activation of
      macrophage phagocytosis. Subchronic exposure to mercuric chloride resulted in a
      transient (7-14 day) decrease of the lymphoid/total bm cell ratio and affected
      the incidence of splenic T-cell subsets, however, without a clear dose-response
      correlation. The B-cell population in spleen and maturation patterns of B-cells
      in bm appeared to be unaffected by the mercury exposure. Overall, cytometric
      analysis of lymphoid cell subsets in murine bone marrow revealed transient and
      subset-non-specific cell fluctuations after subchronic exposure to inorganic
      mercury.

PMID- 8262696
TI  - Inhaled isobutyl nitrite compromises T-dependent, but not T-independent, antibody
      induction.
AB  - Habitual abuse of nitrite inhalants has been linked in epidemiological studies
      with seropositivity to human immunodeficiency virus and, separately, with
      Kaposi's sarcoma among AIDS patients. Mice exposed to isobutyl nitrite in an
      inhalation chamber for 45 min/day for 14 days had depressed IgM and IgG antibody
      responses. The inhibition was dose-dependent at 750-900 ppm, but antibody
      responses were increased at an intermediate (600 ppm) dose. Gender differences in
      immunotoxicity were not observed. Antibody responses to a T-independent antigen
      (DNP-ficoll) were not affected by the immunotoxic exposure, suggesting that B
      cells were refractory to the toxic exposure. Toxic exposure to isobutyl nitrite
      did not selectively deplete a particular spleen cell population, but caused
      equivalent reductions of T-cells and B-cells. Finally, exposed mice remained
      immunocompromised for 3-5 days after terminating exposures. Normal immune
      responses returned by 5-7 days, suggesting that inhibition of cellular function
      was reversible.

PMID- 8262697
TI  - IL-4 receptor expression by SAC-activated B-lymphocytes: its role in B-cell
      proliferation and the effect of cyclosporine (CsA), prednisolone and verapamil.
AB  - Expression of the IL-4 receptor was studied in a highly purified population of
      human B-lymphocytes stimulated by Staphylococcus aureus, cowan I (SAC). Flow
      cytometric analysis showed that incubation with SAC in the absence of detectable
      levels of IL-2, IL-4 and IL-6 resulted in a striking increase in cellular binding
      of IL-4. The SAC-stimulated B-cells responded to exogenous IL-4 by DNA synthesis.
      This response was unaffected by CsA or prednisolone, but was inhibited by the
      Ca2+ channel blocker verapamil.

PMID- 8262698
TI  - Advances in physiology and biomechanics of rowing.

PMID- 8262699
TI  - Influence of exercise intensity and duration on post-exercise pulmonary diffusion
      capacity.
AB  - Pulmonary diffusion capacity has been observed to be reduced by approximately 14%
      2h after 4-6 min of maximal exercise. The purpose of this study was to determine
      if the decrease in pulmonary diffusion capacity also occurs when the duration of
      exercise intensity is shorter or when the exercise intensity is lower. We
      measured pulmonary diffusion capacity using the single breath method in 12
      competitive rowers 22 (16-31) years old, 70 (56-100) kg body weight, and 180 (171
      193) cm body height under two conditions: (1) 2h after 6 min of rowing at both
      61% (58%-68%) and 76% (73%-78%) of maximal oxygen uptake; (2) 2h after 1, 2, or 3
      min of all-out rowing. Values are presented as medians with ranges. Pulmonary
      diffusion capacity was reduced by 6% (2%-17%) after 6 min of rowing at 61% and by
      10% (-7%-21%) after 6 min of rowing at 76% of maximal oxygen uptake (p < 0.03).
      Pulmonary diffusion capacity was reduced by 7% (3%-19%), 8% (2%-17%) and 7% (1%
      16%) after 1, 2, and 3 min of all-out rowing (p < 0.01). We conclude that
      submaximal exercise at 61% of maximal oxygen uptake will affect pulmonary
      diffusion capacity following exercise as will shorter duration of maximal
      exercise. Although the mechanism for this fall in pulmonary diffusion capacity is
      unclear, the fact that it occurs after even mild exercise makes a significant
      change in pulmonary capillary membrane integrity or subclinical pulmonary edema
      unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262700
TI  - Pulmonary mechanics and entrainment of respiration and stroke rate during rowing.
AB  - During rowing, the respiratory musculature is confronted with dual demands:
      assisting the propulsive force generation and as the effector for ventilatory
      control. We determined the pulmomechanical and breathing pattern features of
      rowing-induced hyperpnea in five national class rowers (18 years old). Each
      subject performed incremental exercise on a mechanically braked rowing ergometer.
      Power was increased by 50 W each 3 min, from 150 W to 350 W. Breathing was
      through a low-resistance, ultrasonic flow-sensing device. Respired gas
      concentrations were measured by mass spectrometry. Intrapleural pressure (Pp1)
      was monitored by an esophageal balloon. Ventilation (VE) increased by increasing
      tidal volume (VT) at constant breathing frequency (fb). Above approximately
      701.min-1 there was little change in VT and further increase in VE was dominated
      by fb. Two breathing patterns were identified: (1) one expiration per stroke and
      one inspiration during recovery and (2) one complete breath during stroke and one
      breath during recovery. Stroke frequency (fs) and fb increased in concert, i.e.,
      all subjects entrained their breathing. Pp1 indicated dynamic airway compression
      during exhalation at high work rates and also that VT did encroach upon the flat
      part of the compliance curve. With the constrained VT, the demand for increased
      fb to effect the hyperpneic response at high work rates may result in an
      entrainment of the stroke frequency to that of breathing.

PMID- 8262701
TI  - Heart rate, blood lactate, and catecholamines during ergometer and on water
      rowing.
AB  - The heart rate, blood lactate, and catecholamine responses to rowing on a
      Gjessing ergometer and in a single scull on the water were compared. Seventeen
      rowers performed a multistage step test on the ergometer as well as low and high
      intensity endurance rowing on the water. Seven oarsmen (six with determinations
      of free plasma adrenaline and noradrenaline) rowed on the ergometer with the same
      heart rate and duration as on the water. During ergometer endurance rowing, heart
      rate, lactate, and adrenaline were not significantly different from boat rowing,
      while plasma noradrenaline was higher. However, at similar lactate levels, heart
      rate during rowing on the water was approximately 10 beats.min-1 higher than
      during the ergometer multistage step test, due to the different duration of
      exercise. Heart rate values based on determination of lactate threshold can be
      taken as recommendations for low and high intensity endurance training on water.
      However, because of individual variations in the heart rate-lactate relationship
      between rowing on the ergometer and in the boat, field evaluation is recommended.

PMID- 8262702
TI  - Metabolic and hormonal reactions during training in junior oarsmen.
AB  - This study evaluated strain reactions in young athletes (mean age: 17.6 years).
      Of 35 male rowers, 21 were selected by rowing ergometer tests to take part in a
      26-day training camp before the World Championships in 1989. Blood samples were
      obtained in the morning of the day after rowing ergometer tests and on the 16th
      and 26th day. Cortisol (C), testosterone (T), sexual-hormone-binding globulin
      (SHBG), urea and creatine kinase (CK) were determined in serum and free
      testosterone (FT) was calculated. In the nonselected rowers C was 10% higher, FT
      20% lower, and CK 42% higher compared to the selected rowers. During training, C
      was related to the intensity of training. It remained constant in phase 1 (12
      days, increased volume of training) and increased in phase 2 (10 days, decreased
      volume and higher intensity). FT decreased in phase 1 and increased in phase 2.
      Urea showed a close relationship to training volume. CK levels decreased during
      the training volume. CK levels decreased during the training period as an
      adaptation to the training. Despite a high training load, there were no
      indications of overstrain reactions in these young athletes.

PMID- 8262703
TI  - Performance and blood lactate on Gjessing and Concept II rowing ergometers.
AB  - The Gjessing (GE) and the wind resistance (Concept II, CII) rowing ergometers
      were compared in 11 trained subjects during incremental exercise. Maximum power
      was 255 (200-370) W on GE, but 294 (204-393) W in CII (median and range, p <
      0.05). If power was directly measured by a strain gauge and a displacement
      transducer in the CII, a 5.1% (3.2%-7.8%) higher maximum performance was obtained
      (314 [223-413] W, p < 0.05). Maximum stroke rates were higher in GE (33 [27
      37]/min) than in CII (29 [24-35]/min, NS). Blood lactate increased faster with
      work rate and lactic anaerobic threshold was therefore lower in GE. Blood lactate
      was higher for every heart rate for GE compared to CII. This suggests higher
      anaerobic effort in GE rowing.

PMID- 8262704
TI  - Physiological aspects of training in rowing.
AB  - At the start of a rowing race, the boat is accelerated and the force on the oars
      reaches between 1000 and 1500 N. During the race, the speed is maintained at a
      lower level with a peak rowing force of 500-700 N for 210-230 strokes for about
      6.5 min. Rowers are adapted to this effort by a large muscle mass and high
      metabolic capacities. The muscles of successful rowers demonstrate 70%-85% slow
      twitch fibers. Both slow- and fast-twitch fibers have increased oxidative enzyme
      activities reflecting elevated number and density of mitochondria. Rowing force
      and boat velocity correlate to maximal oxygen uptake (VO2) which reaches 6.0
      6.61.min-1 (65-70 ml.min-1. kg-1) and to the VO2 during a race. In turn, the VO2
      during a race is related to slow-twitch fibers content of the muscles, also to
      the aerobic-anaerobic threshold (AAT) and inversely related to the maximal blood
      lactate level. The AAT is 80%-85% of maximal performance in highly trained
      rowers. In successful rowers training intensity is 70% -90% of the training time
      below the AAT. Training eliciting a blood lactate above 4.0 mmol/l, sprint
      training and athletics training complete the training schedule, which may reach
      1000 h, or 5000-7000 km per year.

PMID- 8262705
TI  - Force-time characteristics of the rowing stroke and corresponding physiological
      muscle adaptations.
AB  - The force-time characteristics of the rowing stroke was examined in a coxless
      pair. Sixteen highly trained rowers were evaluated in their usual training
      positions (stroke or bow). Stroke rowers had higher stroke speed and stroke force
      in the first part of the stroke than bow rowers. This finding was more prominent
      during competition speed rowing than during endurance training. Higher blood
      lactate levels and lower base excess were found at both speeds in stroke rowers.
      During and incremental ergometer rowing test, lactate performance curves were
      shifted to the left in the stroke rowers. Analysis of morphometric data in the
      left deltoid muscle demonstrated higher FT fiber content and lower oxidative
      fiber capacity and fiber areas in the stroke rowers. The results demonstrate
      adaptation to years of training in a specific boat position.

PMID- 8262706
TI  - Three-axes gyro system quantifying the specific balance of rowing.
AB  - Stabilizing the balance of the boat is a main task of the rowing motion. This
      leads to movements which are asymmetrical relative to the boat's plane of
      symmetry. The three-dimensional motion of the boat should be measured when
      investigating the elements of keeping the balance. This spatial motion must be
      described by the three components of the translational velocity and the three
      components of the angular velocity. The latter values can be measured using
      gyros. A system was developed which employs these sensors. The system is small
      and light enough to be used aboard a single scull. Measurements which were
      obtained using this system conclude the article. They illustrate some factors of
      importance for the stability of the boat and demonstrate the suitability of the
      system presented.

PMID- 8262707
TI  - Assessment of rowing efficiency.
AB  - Between one-fourth and one-third of the energy in rowing is lost to the flow of
      water around the blade which decreases efficiency, i.e., the ratio of effective
      energy to expended energy. Hitherto the assessment of this hydrodynamic rowing
      efficiency was difficult and could not be achieved as a function of rowing angle
      and time. By recording the path of the blade and the forces acting on the blade a
      method was found, which is practical to use and renders the hydrodynamic
      efficiency at each instant of the rowing action. The assessment is based on the
      measurement of boat velocity, angular velocity of the oar or scull, and moment
      exerted by the rower. These parameters are measured, digitized, and stored in the
      boat for later computation on shore.

PMID- 8262708
TI  - Peak force, velocity, and power during five and ten maximal rowing ergometer
      strokes by world class female and male rowers.
AB  - On a Gjessing rowing ergometer 20 A- and B-squad women (age 21.6 +/- 2.3 years,
      height 183.6 +/- 2.8 cm, weight 75.6 +/- 2.6 kg) and 81 A-squad men (age 24.6 +/-
      2.1 years, height 194.8 +/- 3.3 cm, weight 92.8 +/- 2.7 kg) performed five and
      ten maximal strokes with a brake load of 3.0 kp; additionally, the women
      performed a 6-min maximal test (3.0 kp brake load). During the rowing stroke the
      peak force was measured with a strain gauge, while the peak velocity was
      determined with an ultrasound echo system. From these values the peak power was
      calculated. Regardless of sex, there was a relatively constant relationship
      between peak force and velocity, according to the principle of Hill. For the men
      the maximal peak force for five and ten strokes was 1350 N, the maximal peak
      velocity 3.80 m/s, and the maximal peak power 3230 W. The corresponding values
      for the women were 1020 N, 2.90 m/s, and 1860 W, respectively. With the exception
      of the strokes at the beginning, at no time during the 6-min maximal test was
      more than 65%-70% of the maximal force applied. Peak force decreased from the
      first stroke to the last stroke. The slightly increased peak power during the
      last 25 s of the test was caused solely by an increase in peak velocity.

PMID- 8262709
TI  - Diagnostic methods and treatment modalities of dry eye conditions.
AB  - One may view dry eye conditions as a group of diseases in which the ocular
      surface is adversely affected. Tear film instability invariably leads to some
      degree of cellular surface damage over the cornea and conjunctiva. In turn,
      ocular epitheliopathy may adversely affect tear film stability. The clinical
      presentation of the disease may not yield a clue as to its etiology. In recent
      years considerable progress was made both in the diagnosis and the treatment of
      the disease and promising studies are planned or are underway. The diagnostic
      techniques can be divided into four groups. The first is concerned with the
      clinical presentation. The second is concerned with the bulk properties of the
      aqueous tears including dynamic characteristics, composition, and colligative
      properties. The third is tear-film related and includes the film break-up time,
      evaporation rate, and lipid abnormality. The fourth is concerned with the ocular
      surface and includes vital staining, impression cytology, and surface microscopy.
      The most promising attempts are being made in the second group by attempting to
      elucidate the role of enzyme and enzyme activator activity and inhibitor contents
      as well as the tear protein profiles and correlating them with the specific
      disease states. The treatment modalities belong to three major groups aside from
      surgical intervention; the supplementation, preservation, and the stimulation of
      tears. The modern version of tear supplementation is expected to include the
      topical use of efficacious aqueous formulations that typically contain film
      stabilizing polymers, nutrients, and/or--in the future--biochemically active
      ingredients such as enzyme activators and inhibitors.

PMID- 8262710
TI  - Hypopyon--an unusual sign in acute angle-closure glaucoma.
AB  - The appearance of a hypopyon is an extremely uncommon finding in acute angle
      closure glaucoma and only a few cases have been previously reported in the
      literature. We report a fifty-year-old female who, following a recent
      bereavement, presented with classical features of acute angle-closure glaucoma
      and a hypopyon. The eye developed a glaukomflecken and the patient underwent
      trabeculectomy, extracapsular cataract extraction and intraocular lens
      implantation with good post-operative results. Because hypopyon in acute angle
      closure glaucoma is rare and may cause diagnostic confusion and hence therapeutic
      difficulties, this case is described to highlight this unusual clinical sign.

PMID- 8262711
TI  - Endogenous Aspergillus endophthalmitis in an immunocompetent individual.
AB  - We present an unusual case of Aspergillus fumigatus endogenous endophthalmitis in
      a 27 year old Hispanic male with no history of ocular trauma, surgery,
      hematologic malignancy, compromised immune system, or intravenous drug use. The
      patient presented with a two-day history of pain, redness, and visual acuity of
      bare count fingers in his right eye. He was originally suspected of having
      toxoplasmic retinochoroiditis, but clinically worsened on systemic anti
      toxoplasma medication and corticosteroids. He subsequently underwent pars plana
      vitrectomy and treatment with intravenous and intravitreal amphotericin B.
      Aspergillus fumigatus was isolated and identified in the vitreous aspirate. With
      aggressive medical and surgical management, he eventually regained visual acuity
      of 20/30 in his right eye. This case illustrates the occurrence of endogenous
      Aspergillus endophthalmitis in a patient with no history of intravenous drug use,
      ocular trauma, or compromised immune system, and successful outcome with combined
      medical and surgical management.

PMID- 8262712
TI  - Primary posterior chamber IOL implantation in penetrating ocular trauma.
AB  - This paper describes the experience of primary cataract extraction and posterior
      chamber IOL implantation in 11 eyes with penetrating ocular trauma. The primary
      surgical procedure consisted of repair of corneoscleral laceration, cataract
      extraction, posterior chamber IOL implantation and in certain cases, removal of
      intraocular foreign body and vitrectomy. 10 out of 11 cases had a post operative
      visual acuity of 6/18 or better, with 9 out of 11 having a post operative visual
      acuity of 6/12 or better. One case initially had a visual acuity of 6/24 but
      later developed retinal detachment with a visual acuity of 'hand movements'.
      Another patient developed a small localised retinal detachment during the tenth
      postoperative month but with successful surgery, attained a visual acuity of 6/6.
      The encouraging results suggest that this procedure may be recommended in
      carefully selected cases, under the management of an experienced surgeon.

PMID- 8262713
TI  - Colour vision in retinitis pigmentosa. Influence of cystoid macular edema.
AB  - In retinitis pigmentosa patients the effect of cystoid macular edema on colour
      vision was studied. The occurrence of cystoid macular edema decreases with
      increasing colour vision defect. The mutual proportion of the main types of
      colour vision defects remains stable until visual acuity has dropped to 0.5; at
      lower VA levels the number of red-green defects increases. Neither the finding of
      a blue-yellow colour vision defect in FM100 Hue testing nor the appearance of
      anomaloscopic pseudoprotanomaly is influenced by cystoid macular edema. The
      authors conclude that cystoid macular edema in retinitis pigmentosa patients
      mainly affects visual acuity and not colour vision. They also noted a familial
      occurrence of cystoid macular edema.

PMID- 8262714
TI  - Ocular fluorometry: standardization and instrumentation development. A Concerted
      Action in the European Community (EUROEYE).
AB  - A Concerted Action on Ocular Fluorometry, stressing standardization and
      instrumentation development has been funded by the European Community. Agreement
      was reached on harmonization of protocols. The results obtained show that the
      protocols proposed for Clinical Ocular Fluorometry were generally appropriate and
      may be followed closely, with reproducible and meaningful results. In each group,
      areas for improvement could, however, be detected, particularly regarding
      facility of use of the newly developed softwares. The success of the ECNOF was
      very rewarding and every effort is being made to consolidate this success in the
      publication and dissemination of the agreed guidelines and results. The field of
      Ocular Fluorometry appears to have even more potential than was apparent at the
      beginning of this Concerted Action. The needs for instrumentation development
      have been clarified and four main directions where progress has been achieved are
      identifiable: spectral fluorescence analysis of naturally occurring ocular
      fluorophores, light scattering analysis of ocular structures and fluids, improved
      axial resolution for better quantification of ocular permeabilities and, finally,
      development of simple routine clinical instrumentation. Corneal and lens natural
      fluorescence appear extremely promising as indicators of disease status,
      particularly in diabetes. Blood-retinal barrier permeability has the potential to
      become a screening test isolating the eyes at risk for developing diabetic
      blindness and, therefore needing closer follow-up and earlier treatment. Light
      scattering methodologies particularly in association with ocular fluorometry, may
      allow improved monitorization of chronic inflammation, better therapeutical
      management of a variety a sight-threatening diseases.

PMID- 8262715
TI  - The scope of the cataract problem in the Middle East and the Mediterranean.
AB  - The region is characterized by diversity in cultural, political, economic and
      health conditions. Blindness in the region varies from 6.4% to 0.2% with cataract
      ranking highly as an underlying cause. There is a need to develop national
      policies to deliver affordable, technically suitable, and cost effective
      management plans to reduce cataract. Economic, demographic, health, and manpower
      statistics are essential information to be considered in formulating such
      policies.

PMID- 8262716
TI  - Prevalence and causes of visual impairment and blindness in the south western
      region of Saudi Arabia.
AB  - A population-based survey of the prevalence of major causes of blindness and
      visual impairment was conducted in Bisha region, Saudi Arabia. Overall, 2882
      people were examined. The prevalence of blindness (visual acuity of < 3/60 in the
      better eye with best available correction) was 0.7% and the prevalence of visual
      impairment (visual acuity < 6/12 but > or = 3/60 in the better eye with best
      available correction) was 10.9%. Cataracts were responsible for 52.6% of
      blindness and 20.6% of visual impairment. Refractive errors accounted for 67.9%
      of visual impairment. Proper management of cataracts and correction of refractive
      errors will cure 73.6% of blind subjects and 88.5% of visually handicap people in
      this part of the world.

PMID- 8262717
TI  - Effect of systemic adenosine infusion on capillary flow and oxygen pressure
      distributions in skeletal muscle of the rabbit.
AB  - The aim of this study was to investigate the effect of systemic adenosine (ADO)
      infusion on blood flow and oxygenation at the capillary level in skeletal muscle
      in order to estimate oxygen demand. In anesthetized rabbits, a multiwire
      microelectrode was placed on the left vastus medialis muscle surface, and was
      used for capillary flow (determined by hydrogen clearance) as well as for oxygen
      pressure (PtO2) measurements. Laser Doppler flowmetry (LDF) was also used on the
      contralateral muscle surface for regional microcirculatory blood flow
      measurements. ADO infusion (50-100 micrograms/kg/min) was given in a central
      vein. During the ADO infusion the mean arterial blood pressure decreased from 81
      +/- 5 (mean +/- SD) to 64 +/- 4 mmHg (a 21% decrease) (p < 0.001), while
      capillary flow decreased by 37% from a mean value (relative units) of 1.0 +/-
      0.84 during control to 0.63 +/- 0.72 (p < 0.001). During ADO infusion there was
      an increased flow heterogeneity. The mean PtO2 increased by 29% from 5.6 +/- 2.3
      to 7.2 +/- 2.2 kPa (p < 0.001) associated with decreased oxygen heterogeneity. A
      43% reduction of the relative calculated local oxygen consumption was found
      during ADO infusion (p < 0.05). The LDF flux decreased by 7% (p < 0.05). We
      conclude from these results that systemic adenosine infusion decreases skeletal
      muscle capillary blood flow and in parallel increases the oxygen pressures. This
      can be explained by a redistribution of the capillary blood flow as well as a
      reduction in skeletal muscle oxygen demand.

PMID- 8262718
TI  - Effect of leukocyte adhesion and microvascular permeability on capillary
      perfusion during ischemia-reperfusion injury in hamster cheek pouch.
AB  - The role of leukocyte sticking and permeability changes in the variation of
      perfused capillaries induced by ischemia reperfusion was studied in the hamster
      cheek pouch microcirculation. The drugs utilized were the antiperoxidative agents
      allopurinol, the calcium antagonists verapamil and diltiazem, and phenidone and
      adenosine, which inhibit leukotriene formation as well as leukocyte adhesion to
      the endothelium. The microvasculature was visualized by a fluorescence technique.
      Ischemia was induced by clamping the cheek pouch for 30 minutes followed by 30
      minutes of reperfusion. The increase in permeability, the perfused capillary
      length and the number of adhering leukocytes to venular vessel wall were
      measured. Ischemia and reperfusion were associated with increased permeability,
      increased number of leukocytes sticking to the venular wall, and decreased number
      of functional capillaries. Microvascular injury evidenced by increased
      permeability was apparent in the first 5 min of ischemia. All the drugs decreased
      the number of leukocytes sticking to the venular wall; allopurinol, verapamil and
      adenosine reduced the increase in permeability, whereas phenidone and diltiazem
      were effective only during ischemia. In addition verapamil and adenosine
      preserved capillary blood flow during reperfusion. In conclusion, leukocyte
      sticking is correlated with increased microvascular permeability, but not with
      decreased perfusion of the capillary bed. These data suggest that leukocytes did
      not play a prominent role in the reduction of functional capillaries at the end
      of reperfusion.

PMID- 8262719
TI  - The influence of hemorrhage on liver microcirculation of the cirrhotic rat.
AB  - Bleeding from esophageal varices is highly lethal in cirrhotics, the main cause
      of death being liver failure. Because adequate hepatic perfusion is a prerequest
      for the maintenance of liver function, the present study was designed to evaluate
      the influence of hemorrhagic shock on liver microcirculation in rats with portal
      hypertension due to cirrhosis of the liver induced by CCl4. In 16 cirrhotic rats
      and an equal number of controls, hepatic microcirculation was continuously
      assessed--by means of laser-Doppler flowmetry, through a self-adhesive probe
      attached to the liver surface, before and during a 15 min period of arterial
      hypotension (40 mmHg) induced by blood withdrawal. Our findings revealed that
      immediately following hemorrhage there is a statistically significant reduction
      of microcirculation in cirrhotics versus controls. The results of this study
      assist in the better understanding of the hemodynamic conditions which prevail in
      the cirrhotic liver during the first minutes of hemorrhage.

PMID- 8262720
TI  - Routine anaerobic bacterial culture and systemic antibiotic usage in the
      treatment of adult periodontitis: a 6-year longitudinal study.
AB  - This investigation evaluated the efficacy of obtaining baseline culture and
      sensitivity data on a routine basis from the patient with adult periodontitis.
      Patients diagnosed with chronic adult periodontitis, rapidly progressive
      periodontitis, or refractory periodontitis were followed for up to 6 years. More
      than 95% of patients with chronic adult periodontitis were successfully treated
      with mechanical therapy alone. Approximately one half of the patients with
      rapidly progressive periodontitis were treated successfully without antibiotics.
      All of the patients with refractory periodontitis required systemic antibiotics
      as part of treatment. Most patients with chronic adult periodontitis exhibited
      one or two species of organisms at baseline, and these organisms were eliminated
      or reduced to low levels by mechanical therapy. In contrast, patients with
      rapidly progressive or refractory periodontitis consistently demonstrated
      multiple species and required systemic antibiotics in conjunction with mechanical
      therapy to alter the subgingival microbial milieu. Routine culturing and
      antibiotic therapy is contraindicated in patients with chronic adult
      periodontitis, but may be beneficial for successful treatment of patients with
      rapidly progressive or refractory periodontitis.

PMID- 8262721
TI  - Placement of hydroxyapatite-coated endosseous implants in fresh extraction sites:
      a case report.
AB  - This case illustrates the use of the principles of guided tissue regeneration to
      achieve osseointegration of an endosseous dental implant. One implant was placed
      immediately, with hydroxyapatite and a barrier membrane, in an extraction site,
      while another was placed in a healed site. Eighteen months postinsertion, the
      implant placed in the extraction socket exhibited better maintenance of crestal
      height than did the implant inserted in the healed site.

PMID- 8262722
TI  - Reconstruction of the hard and soft tissues for optimal placement of
      osseointegrated implants.
AB  - Success, as it is usually defined for osseointegrated implants, may leave much to
      be desired in terms of esthetics, phonetics, and function. Optimal occlusal
      function demands that the implant-supported restoration be placed in a position
      that will permit the desired cusp-fossae relations with axial loading. In the
      partially edentulous patient, the implant-supported restoration also should blend
      into the arch form of the adjacent and opposing teeth. From a phonetic viewpoint,
      the natural contour and position of the anterior teeth must be maintained. To
      achieve these goals, it may be necessary to restore the hard and soft tissue
      anatomy vertically and horizontally and to augment or reconstruct the sinus.
      Depending on the circumstances, these measures may be carried out before, during,
      or after implant placement. In this paper, the considerations involved in
      diagnosis and selection of reconstructive technique are outlined.

PMID- 8262723
TI  - Hierarchy of objectives in implant placement to maximize esthetics: use of pre
      angulated abutments.
AB  - Limitations in position, quality, or dimension of bone often require that
      implants be placed in a nonideal axial inclination. Use of preangulated abutments
      may be the method of choice when anatomic limitations preclude the axial
      placement of an implant. This paper discusses the indications for and advantages
      of the use of preangulated abutments to fulfill esthetic and functional
      objectives.

PMID- 8262724
TI  - Effect of calculus and irrigator tip design on depth of subgingival irrigation.
AB  - This study addressed three factors that may affect the penetration of medicaments
      into periodontal pockets: calculus, ejection site pressure, and irrigator tip
      design. Ejection site pressure for the Max-I-Probe, the Viadent and Water-Pik
      tips were determined with a variant of Bernoullis' equation. Depth of irrigant
      penetration was determined by delivering disclosing solution supragingivally and
      subgingivally. Following irrigation, assessed teeth were extracted and the
      percentage of pocket penetration by the dye was calculated. The Max-I-Probe and
      Viadent tips had significantly greater penetration than did the Water-Pik tip.
      Furthermore, calculus deposits reduced irrigation penetration in deep pockets (7
      to 10 mm). Ejection site pressures of the three tips ranged from 0.10 to 4.80
      psi. The ejection site pressure of the Max-I-Probe side-port delivery system was
      lower than that of the other two systems. Results indicated that subgingival
      calculus, irrigator tip design, and placement of the tip affect the depth to
      which drugs can be delivered subgingivally.

PMID- 8262725
TI  - Is there a role for vindesine in the treatment of non-small cell lung cancer?
AB  - Vindesine is a semisynthetic derivative of vinblastine which has been evaluated
      in clinical studies since the late 1970's. The literature on vindesine in the
      treatment of non-small cell lung cancer has been reviewed and all aspects of
      vindesine treatment in this disease has been covered. It is concluded that
      vindesine as a single agent yields a response rate of 18% based on the treatment
      of 295 patients included in phase II trials (95% confidence limits 13%-22%). No
      difference was observed among the three major histologic types of non-small cell
      lung cancer. In phase III trials, the response rate and confidence limits are at
      a similar level. Combination chemotherapy including vindesine plus cisplatin
      ranks among the most active treatments in non-small cell lung cancer and is as
      active as etoposide plus cisplatin, both with respect to response rate and
      survival. It has not been documented that the addition of one or two other drugs
      to the combination of vindesine yields an increase in survival. When best
      supportive care was compared with a combination of vindesine plus cisplatin, the
      group with chemotherapy was attributed a survival advantage in all three studies
      published, and the difference was statistically significant in two of these three
      studies. Thus, vindesine has a well documented activity in non-small cell lung
      cancer and ranks among the most active single agents in this disease. Vindesine
      is also part of several active combination chemotherapies among which the
      combination of vindesine plus cisplatin is particularly interesting, because it
      has been repeatedly shown to prolong survival as compared to supportive care.
      Especially this latter point leads to the conclusion that there is a role for
      vindesine in the treatment of non-small cell lung cancer. However, the concept of
      chemotherapy in this disease remains investigational even though the advances
      seen in recent years clearly merit further studies.

PMID- 8262726
TI  - Plasma pharmacokinetics, tissue disposition, excretion and metabolism of
      vinorelbine in mice as determined by high performance liquid chromatography.
AB  - We have investigated the pharmacokinetics of the investigational semi-synthetic
      vinca alkaloid vinorelbine (navelbine, NVB). The analyses have been performed by
      using a sensitive and selective method based on ion-exchange normal phase high
      performance liquid chromatography with fluorescence detection combined with
      liquid-liquid extraction for sample clean-up. Pharmacokinetic studies were
      performed in male FVB mice receiving 12 mg/kg NVB through intravenous injection.
      The results have been compared to those obtained for vinblastine (VBL). The
      plasma pharmacokinetics of NVB can be described by a three compartment model. The
      elimination half-life is significantly longer and the plasma AUC values higher
      for NVB compared to VBL. This is reflected in tissues, where, 24 hr after drug
      administration, the concentration of NVB is 5 to 10-fold higher compared to VBL.
      Qualitatively, the tissue distribution and retention of the drugs is very
      similar. The drug concentrations in most tissues decline parallel with the
      circulating plasma levels, whereas prolonged retention is found in tissues of
      lymphatic and testicular origin. Deacetylation yielding deacetylnavelbine (DNVB)
      is the primary metabolic route for NVB. This cytotoxic metabolite accounts for a
      substantial part of the overall disposition of drug. Only 58% of the administered
      dose is excreted in the urine (17%) and faeces (41%) as NVB or DNVB. No other
      metabolites have been detected.

PMID- 8262727
TI  - VRCTC-310--a novel compound of purified animal toxins separates antitumor
      efficacy from neurotoxicity.
AB  - Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to
      produce a unique natural product (VRCTC-310) currently under investigation as an
      antitumor agent by the National Cancer Institute. In vitro, it has demonstrated
      cytotoxic disease specificity and a unique mechanism of action when submitted to
      COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties
      of crotoxin which allowed comparison of several schedules of fixed and escalating
      daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of
      tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg
      and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites
      of i.m. injection was noted, animal weight loss was negligible and there were no
      other signs of adverse toxicity. This natural product represents a new, membrane
      interactive anticancer agent which produces a unique spectrum of cytotoxicity in
      vitro and which has demonstrated interesting in vivo antitumor efficacy.

PMID- 8262728
TI  - Chemotherapy of mammary carcinomas arising in ras transgenic mice.
AB  - Transgenic female mice carrying the V-Ha-ras transgene linked to the MMTV
      promoter, which developed mammary carcinomas, were treated with selected cancer
      chemotherapy drugs. Agents were administered i.p. on a daily x 9 schedule when
      mice developed tumors that were 50-100 mg in size. Drugs which are clinically
      effective against breast cancer were quite efficacious in the transgenic model at
      their maximum tolerated dose. Doxorubicin produced excellent responses in tumor
      bearing transgenic mice, with several mammary carcinomas undergoing tumor
      shrinkage. Two anthrapyrazoles, DuP 937 and DuP 941, novel anticancer drugs with
      phase 2 activity against breast cancer, were as effective as doxorubicin in the
      oncomice. Mitoxantrone, a synthetic agent with some properties similar to the
      anthracyclines, also had antitumor activity, but not as pronounced as obtained
      with doxorubicin or the anthrapyrazoles. Cisplatin, a drug with limited use in
      human breast cancer, only caused modest antitumor responses. A computerized data
      analysis method based on the area under the tumor growth curve was developed to
      better quantitate the data and provide statistical information. This quantitative
      analysis confirmed the high statistical significance of the activity of
      doxorubicin or the anthrapyrazoles in the ras transgenic model, and defined an
      excellent dose response relationship for each drug tested. Our results suggest
      that the ras transgenic model may be useful for identifying drugs that have
      efficacy for breast cancer in women.

PMID- 8262730
TI  - Phase I trial of 5-fluorouracil by 24-hour infusion weekly.
AB  - A novel schedule of 5-fluorouracil administration has been developed for
      biochemical modulation studies. In combination with the pyrimidine synthesis
      inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated
      weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5
      fluorouracil as a single agent on this schedule, we treated 26 patients at doses
      ranging from 2800 to 3400 mg/m2 per week. Two-thirds of the patients had failed
      previous therapy, and most were symptomatic from their disease. Over half of the
      patients had metastatic colorectal cancer. The dose-limiting toxicity was
      diarrhea: Grade 3 or 4 toxicity occurred at every level tested. Twenty-two of the
      26 patients required therapy interruption because of toxicity. The severity of
      this toxicity indicated that escalation of 5-fluorouracil on this schedule beyond
      the 2600 mg/m2 known to be tolerated in the PALA-containing regimen, would be
      impractical. Two patients, both with previously untreated colorectal cancer, had
      partial remissions lasting three and five months respectively. This dose-intense
      schedule of 5-fluorouracil administration will be explored further in large-scale
      randomized trials.

PMID- 8262729
TI  - A phase I clinical and pharmacological profile of dacarbazine with autologous
      bone marrow transplantation in patients with solid tumors.
AB  - Dacarbazine (DTIC) is a chemotherapy drug which has antitumor activity at
      standard doses, exhibits a steep dose-response effect in vitro, and is associated
      with relatively few non-hematologic toxicities. These characteristics suggest a
      potential role for this drug in bone marrow transplant preparative regimens. To
      pursue this hypothesis, 16 patients with refractory solid tumors were enrolled in
      a phase I study of single agent DTIC to determine the dose of DTIC requiring bone
      marrow reinfusion and to define the dose-limiting toxicity and maximum tolerated
      dose when given with autologous bone marrow rescue. Pharmacokinetics were
      evaluated at the 4394 mg/m2 dose level. The marrow requiring dose was 2000 mg/m2
      when given as a single intravenous (i.v.) infusion. The extramyeloid dose
      limiting toxicity of DTIC was hypotension, with the maximum tolerated dose of
      DTIC being 3380 mg/m2 when given with bone marrow transplantation (BMT). Other
      toxicities were transient and tolerable. At 4394 mg/m2 of DTIC, plasma
      concentrations declined biexponentially with a terminal half-life of 3 hours. The
      mean clearance was 10.6 L/hr/m2 with a volume of distribution at steady state of
      37.5 L/m2 and a mean maximum plasma concentration of 150 mcg/ml. One patient with
      melanoma developed a partial response of short duration after receiving 2600
      mg/m2 of DTIC. Dacarbazine can be significantly dose escalated with an acceptable
      toxicity profile, when given with BMT. Future trials should focus on the addition
      of this drug to current BMT preparative regimens used for the treatment of
      patients with lymphoma.

PMID- 8262731
TI  - Mitoxantrone (dihydroxyanthracenedione) in acute leukemia. An evaluation of two
      treatment schedules by the Southwest Oncology Group.
AB  - Fifty-eight evaluable patients with acute leukemia were treated with Mitoxantrone
      (DHAD) according to two schedules: 14 mg/M2 as a single I.V. pulse dose
      administered three-week intervals, and 4 mg/M2/day for five days every three
      weeks. Six of 58 patients achieved a complete remission. One complete remission
      and 1 partial remission were observed among 26 patients treated with the single
      pulse schedule. Five (16%) complete remissions were attained among 32 patients
      treated on the daily x 5 schedule. Responses were observed only in patients with
      non-lymphoblastic leukemia. DHAD was very well tolerated with myelosuppression as
      the major toxicity. Nausea and vomiting were minimal. Subclinical cardiac
      toxicity occurred in two patients. This was identified by serial reductions in
      cardiac ejection fractions. DHAD appears to have significant activity in acute
      non-lymphoblastic leukemia with minimal toxicity.

PMID- 8262732
TI  - Phase II evaluation of the sulfonylurea LY186,641 in men with hormone independent
      metastatic prostate cancer.

PMID- 8262733
TI  - Phase II trial of echinomycin for the treatment of advanced renal cell carcinoma.
      A Southwest Oncology Group study.
AB  - Forty-nine patients with metastatic or recurrent renal cell carcinoma were
      treated on a phase II trial of Echinomycin. Treatment consisted of Echinomycin
      1.25 mg/m2 intravenously every 28 days. Among the 47 evaluable patients there
      were no complete responses and only one partial response for an overall response
      rate of 2% (95% confidence interval, 0-11%). Eighteen patients (38%) experienced
      toxicity of grade 3 or worse. The most common toxicities were nausea and
      vomiting. The results of this study indicate that Echinomycin is not sufficiently
      active to warrant further trials for the treatment of renal cell carcinoma.

PMID- 8262734
TI  - Polyethylene glycol conjugated interleukin-2: clinical and immunologic effects in
      patients with advanced renal cell carcinoma.
AB  - Recombinant interleukin-2 (rIL-2) modified with monomethoxypolyethylene glycol
      (PEG IL-2) was utilized in patients with metastatic renal cell carcinoma in two
      separate multi-institutional trials. PEG IL-2 was administered as an I.V. bolus
      days 1, 8, 15, and 22 with cycles repeated every six weeks. The two trials
      employed different dose levels: A) 20 x 10(6) I.U./m2 day 1 followed by 12 x
      10(6) I.U./m2 days 8, 15, 22; and B) 12 x 10(6) I.U./m2 days 1, 8, 15, 22. Thirty
      five patients were entered and 31 were evaluable for response (A-15/18, B-16/17).
      Two of 31 patients had partial responses. Median therapy duration was four weeks
      (range 1-15), and dose reduction for grade III or IV toxicity was required in
      14/35 patients (A-6/18, B-8/17). Toxicity (> or = grade III) seen included:
      hypotension 51%, dyspnea 17%, seizures 6%, and mental status changes 11%. No
      differences in response or toxicity between the two schedules were noted.
      Hematologic changes included lymphocytosis and eosinophilia in the majority of
      patients. PEG IL-2 given once weekly has significant toxicity, and may produce
      tumor regression in patients with renal cell carcinoma.

PMID- 8262735
TI  - Phase II trial of amonafide in advanced pancreas cancer. A Southwest Oncology
      Group study.
AB  - Amonafide is a new synthetic anticancer agent whose mechanism of action is
      through inhibition of macromolecular synthesis as well as DNA intercalation. The
      Southwest Oncology Group (SWOG) has investigated this drug in a phase II study of
      pancreas cancer. Thirty-six patients were registered on this study: of these 29
      were eligible for response evaluation, and 20 received the two cycles required
      for making a response assessment. Patients met the standard phase II criteria of
      no prior chemotherapy, measurable disease and a SWOG performance status of 2 or
      less. Toxicity, predominantly hematologic with significant neutropenia and
      thrombocytopenia, was quite severe. Four treatment related deaths were
      encountered. No responses were seen in thirty-six patients studied. We conclude
      that this drug is not active against adenocarcinoma of the pancreas.

PMID- 8262736
TI  - Evaluation of amonafide in disseminated malignant melanoma. A Southwest Oncology
      Group study.
AB  - Amonafide (AMF), NSC 308847 is an investigational anticancer drug acting as a DNA
      intercalating agent. This paper presents results of a phase II clinical study of
      AMF in disseminated malignant melanoma. Twenty patients, eleven males and nine
      females, with biopsy proven malignant melanoma, performance status 0-2; median
      age 59 (range 29-74), and no previous chemotherapy, were treated with AMF 300
      mg/m2/day by 60 min i.v. infusion for five days repeated every three weeks.
      Fifteen patients had lung (9 patients) and/or liver (8 patients) involvement.
      None had known brain metastasis at entry. All 20 patients were evaluated for
      response and toxicity. Six patients had stable disease and fourteen had
      increasing disease. With 0/20 responses, the upper 95% confidence limit for the
      response rate was 14%. The median survival time was 5.7 months. Hematologic
      toxicity was dose limiting with the incidence of leucopenia 45% and
      thrombocytopenia 20%. The nonhematologic toxicities included nausea and vomiting
      (60%), alopecia (20%), headaches (15%), diarrhea (10%), and phlebitis (10%). We
      conclude that AMF administered at this dose and schedule is not active in the
      treatment of patients with malignant melanoma, previously untreated with
      chemotherapy.

PMID- 8262738
TI  - Phase II trial of carbetimer in metastatic melanoma.
AB  - A phase II study of the synthetic polyelectrolyte Carbetimer 6500 mg/m2 i.v.
      daily for five days every 21-day cycle was conducted in patients with metastatic
      melanoma. No responses were seen in 18 evaluable patients. Two patients had
      stable disease for five months. Toxicity was generally manageable and included
      mild hyperphosphatemia, mild proteinuria, fatigue, pain at the injection site,
      and nausea. Carbetimer is inactive in metastatic melanoma at this dose and
      schedule.

PMID- 8262737
TI  - Phase II trial of piroxantrone in patients with recurrent and metastatic squamous
      cell carcinoma of the head and neck. A Southwest Oncology Group trial.
AB  - Twenty-two patients with recurrent or metastatic squamous cell carcinoma of the
      head and neck were treated with piroxantrone 150 mg/m2 intravenously every 21
      days. There were no objective responses. The 95% upper confidence bound for
      response is 15%. Primary toxicity was hematologic.

PMID- 8262739
TI  - Phase II study on DuP 937 (Teloxantrone) in colorectal carcinoma. A Canadian
      National Cancer Institute Clinical Trial Group study.

PMID- 8262740
TI  - Standards for authorship and publication in academic radiology. AUR Ad Hoc
      Committee on standards for the responsible conduct of research.

PMID- 8262741
TI  - Renal magnetic resonance angiography in the preoperative detection of
      supernumerary renal arteries in potential kidney donors.
AB  - RATIONALE AND OBJECTIVES: Careful evaluation of the renovascular anatomy in
      potential living-related kidney donors is essential regarding the presence of
      accessory renal arteries. Conventional arteriography remains the standard of
      evidence for delineating the renal arterial supply. We assessed the utility of
      two-dimensional phase contrast (PC) magnetic resonance angiography (MRA) in the
      workup of potential living-related renal donors. METHODS: Thirty-nine patients
      were examined with conventional arteriography and MRA, which was performed on a
      1.5-T system using a two-dimensional PC technique in both coronal and axial
      planes (repetition time[TR]/echo time [TE] = 39/8.5 msec; flip 60 degrees; matrix
      256 x 128; field of view, 28 cm2; 2 excitations; first-order gradient-moment
      nulling; 7-mm section with 2-mm overlap). The number of hilar and polar
      supernumerary renal arteries was determined. Hilar supernumerary arteries were
      classified as co-dominant if they were similar in size to the ipsilateral main
      renal artery. RESULTS: Conventional arteriography identified 78 dominant and 13
      supernumerary (3 co-dominant, 10 accessory) renal arteries. Magnetic resonance
      angiography identified the proximal 35 mm of all 78 dominant and the 3 co
      dominant renal arteries. Of the remaining ten (7 polar and 3 hilar) accessory
      vessels, only four were correctly identified with MRA. CONCLUSION: The high error
      rate (60%) suggests that two-dimensional PC MRA, as implemented, should not be
      used in the preoperative evaluation of potential renal donors.

PMID- 8262742
TI  - Brain tissue volume measurement from magnetic resonance imaging. A phantom study.
AB  - RATIONALE AND OBJECTIVES: The authors appraised the accuracy of a method for
      brain volume measurement from magnetic resonance images and evaluated the effects
      of the acquisition matrix, slice thickness, and tissue sampling on the
      measurement error. METHODS: The method uses two magnetic resonance imaging
      sequences to account explicitly for partial volume effects. The accuracy was
      measured with one-, two-, and three-compartmental phantoms that mimic the
      relaxation properties of brain tissues. The sensitivity of the method to section
      thickness was measured by repeated scans of human brain. RESULTS: Using a
      strongly T2-weighted sequence and two-compartmental phantoms, the average error
      was 5%, with 3% error for phantoms larger than 90 mL. In the three-compartmental
      phantoms the error varied from 2% to 7%. Varying the section thickness from 5 to
      10 mm on three-compartmental phantoms and from 2.5 to 10 mm in the human brain
      did not significantly affect compartmental volumes. CONCLUSIONS: The experimental
      study validates the feasibility of monitoring localized volume changes in a three
      compartmental model.

PMID- 8262743
TI  - Experimental hepatic tumor necrosis. Comparison of spin-echo and pulsed
      magnetization transfer contrast magnetic resonance imaging.
AB  - RATIONALE AND OBJECTIVES: We compared the effectiveness of pulsed magnetization
      transfer contrast (MTC) magnetic resonance imaging (MRI) and spin-echo MRI in
      detecting tumor necrosis. METHODS: Adenocarcinoma cells were transplanted in the
      livers of 12 syngenic BDIX rats. To induce various degrees of tumor necrosis, the
      rats were randomly assigned to the following groups: 1) control; 2) localized
      hyperthermia; 3) intralesional cisplatin; and 4) hyperthermia plus intralesional
      cisplatin. At day 7 after treatment, the rats were imaged using a 1.5-T imager
      with 1) multiplanar gradient-recalled echo sequence (MPGR) 500/8/20 degrees with
      and without magnetization transfer contrast (MTC); 2) spin-echo 2500/20,80, and
      3) spin-echo 300/20 pulse sequences. The rats were then sacrificed and pathologic
      specimens were prepared using MR images as guidance. T2 and ratios of signal
      intensity after saturation to signal intensity before saturation (Ms/Mo ratios)
      of the necrotic and granulation tissues and viable tumors were determined in 10
      rats. RESULTS: Compared with standard MPGR images, MPGR images with MTC provided
      better contrast between the pathologic tissues and normal liver. However, T2
      values were more useful than Ms/Mo ratios in distinguishing necrotic areas from
      viable tumor. The T2 values of coagulative necrosis and granulation tissue were
      significantly different from that of viable tumor. No significant difference
      between the Ms/Mo ratios of the different pathologic tissues and normal liver was
      found. CONCLUSION: Pulsed magnetization transfer contrast MRI was inferior to
      spin-echo MRI in distinguishing necrotic from viable tumors in rat livers using
      the pulse sequences described, and none of the sequences studied was thought to
      be reliable enough for this purpose.

PMID- 8262744
TI  - Manganese dipyridoxal diphosphate-enhanced magnetic resonance imaging in the
      evaluation of hepatocyte function.
AB  - RATIONALE AND OBJECTIVES: To determine whether contrast-enhanced magnetic
      resonance imaging can detect ethanol hepatotoxicity in rats. METHODS: Rats were
      treated with a single high dose of ethanol (acute) intraperitoneally or with a
      36% ethanol diet (chronic) for up to 5.5 months. Magnetic resonance imaging was
      performed before and after intravenous administration of manganese dipyridoxal
      diphosphate (Mn-DPDP). RESULTS: Enhancement (acute group) was significantly lower
      in ethanol treated animals on T1-weighted scans (P < .02). Precontrast, a
      significant difference in intensity was seen on T2-weighted scans (P < .01).
      Electron microscopy revealed severe hepatocyte damage. In the chronic groups,
      there was no significant difference in intensity precontrast. Postcontrast,
      enhancement (ethanol group) was significantly lower on T1-weighted scans only at
      2 weeks (P < .05). Electron microscopy demonstrated progressive ethanol
      hepatotoxicity. CONCLUSIONS: Magnetic resonance imaging can distinguish between
      normal and certain types of ethanol damaged livers on T1-weighted scans.
      Enhancement, however, does not correlate with progressive microscopic liver
      damage.

PMID- 8262745
TI  - Effects of vasoconstrictors on rabbit coronary arteries exposed to isotonic ionic
      and nonionic contrast media.
AB  - RATIONALE AND OBJECTIVES: Vasodilation is a well-known side effect of contrast
      media (CM) that is primarily explained by the hyperosmolality of the media. Few
      reports have dealt with the influences of chemotoxicity and ion toxicity on
      vessel tone. We compared the effects of solutions iso-osmolar to plasma of
      iohexol (nonionic monomer), ioxaglate (ionic dimer), diatrizoate (ionic monomer),
      and mannitol on responses to vasoconstrictors (potassium chloride [KCl],
      histamine, and endothelin-1). The aim of this study was to investigate if
      differences in chemotoxicity and ion toxicity could contribute to the changes in
      vessel tone seen clinically during arteriography. METHODS: Segments of rabbit
      coronary arteries were mounted between two L-shaped prongs in tissue baths with
      buffer solution or CM solutions. Their responses to increasing concentrations of
      a vasoconstrictor were measured. The maximal contraction of the vasoconstrictor
      (Emax) and the concentration of the vasoconstrictor causing half maximal
      contraction (EC50) were calculated. RESULTS: Iohexol caused the same changes as
      the nonionic solution of mannitol. The media reduced the actions of KCl,
      histamine, and endothelin-1 to 50% to 60% of their action in buffer. The ionic
      CM, ioxaglate and diatrizoate, caused a more pronounced inhibition of histamine
      and almost totally inhibited the action of KCl. The action of endothelin-1 was
      inhibited to a greater extent by iohexol and mannitol than by ioxaglate and
      diatrizoate. CONCLUSIONS: Different types of iso-osmolar CM interact differently
      with vasoconstrictors. These effects are caused by differences in chemo- and ion
      toxicity. These interactions might contribute to the differences in
      vasodilatation found clinically.

PMID- 8262746
TI  - Repeated intracoronary injections of contrast media. Additive hemodynamic and
      electrophysiologic effects in a dog model.
AB  - RATIONALE AND OBJECTIVES: Coronary arteriography in patients implies several
      selective injections into the coronary arteries. The authors investigate whether
      repeated injections cause additive cardiac hemodynamic and electrophysiologic
      effects in dogs. METHODS: Five repeated injections of 5 mL iohexol (Omnipaque 350
      mgI/mL, Nycomed Imaging AS, Oslo, Norway), ioxaglate (Hexabrix 320 mgI/mL,
      Laboratory Guerbet, Cedex, France), and sodium meglumine-diatrizoate (Renografin
      76 370 mgI/mL, Squibb Diagnostics, Princeton, NJ) were given into the left
      coronary artery in 7 anesthetized dogs and were compared with the effects after a
      5 mL single injection of the same medium. Left ventricular (LV) pressures, LV
      dP/dtmax (inotropy) and epicardial monophasic action potential were recorded,
      from which monophasic action potential duration (MAPD) was measured. RESULTS:
      Repeated injections of ioxaglate and sodium meglumine-diatrizoate did not
      potentiate initial decrease in LV pressures and inotropy, but the secondary
      increase in LV inotropy increased more after repeated injections than after a
      single injection. Repeated injections of iohexol increased LV inotropy more than
      a single injection. All contrast media prolonged MAPD more after repeated
      injections than after single injections. MAPD was prolonged 30 sec after the last
      injection. CONCLUSION: Repeated injections of contrast media cause greater
      cardiac hemodynamic and electrophysiologic effects than a single injection during
      selective coronary arteriography.

PMID- 8262747
TI  - Pharmaceutical properties, biodistribution, and imaging characteristics of
      manganese-mesoporphyrin. A potential hepatobiliary contrast agent for magnetic
      resonance imaging.
AB  - OBJECTIVES: Manganese (III) mesoporphyrin (Mn-mesoporphyrin) was investigated for
      its pharmaceutical properties and magnetic resonance imaging characteristics as a
      potential hepatobiliary contrast agent. METHODS: Solubility, partition
      coefficient, plasma binding, proton relaxation enhancement, biodistribution,
      biliary excretion, liver extraction ratio, and liver enhancement were measured in
      various in-vitro and in-vivo systems. RESULTS: Mn-mesoporphyrin was soluble and
      stable at moderate alkaline pH in phosphate buffer. The octanol/water coefficient
      was 25.98, and the compound was highly protein bound. R1 for water and plasma
      were 1.94 and 2.35 L/mmol sec, respectively. R1 in liver was calculated to be
      15.72 L/mmol sec. Biodistribution studies in rats and mice confirmed
      hepatotrophic properties and biliary excretion was 65% over 24 hours. First pass
      liver uptake was 15%. Magnetic resonance imaging studies showed persistent liver
      enhancement at 0.05 mmol/kg. CONCLUSION: Mn-mesoporphyrin is a lipophilic
      compound that shows potential as a hepatobiliary magnetic resonance contrast
      agent.

PMID- 8262749
TI  - Ultrasound-assisted thrombolysis.
AB  - RATIONALE AND OBJECTIVES: Current use of thrombolytic agents to lyse thrombus,
      though safe, is complicated by stroke, bleeding, and clot embolization. Therapy
      may be protracted, resulting in further ischemia and possible tissue loss.
      Peripheral arterial and graft occlusions often require several hours of
      thrombolytic therapy, which may occasionally exceed 48 hours and may also require
      expensive intensive care monitoring. It is desirable to accelerate clot lysis and
      to thereby reduce the risks and costs associated with the procedure and minimize
      morbidity. In this article, the authors propose the use of intravascular
      ultrasound in conjunction with thrombolytic agents to increase the rate of
      thrombolysis. METHODS AND RESULTS: In-vitro thrombolysis of fresh human blood
      clots was studied with and without urokinase by using continuous wave, 20-KHz
      ultrasound at the power levels 1-2 watts. Loss in weight of each clot was used to
      measure the extent of thrombolysis. Clot lysis was observed when ultrasound and
      thrombolytic agents were used alone. At modest power levels of 1.0 to 1.5 watts
      of ultrasonic energy a significant increase in lysis was observed in conjunction
      with 5,000 units of urokinase. CONCLUSIONS: In the short treatment duration of
      this in-vitro study, 5,000 units of urokinase combined with 20-KHz ultrasound
      energy at 1.0 and 1.5 watts was associated with a greater percentage thrombolysis
      by weight than either urokinase or ultrasound alone.

PMID- 8262748
TI  - Manganese-based liposomes. Comparative approaches.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to further develop and
      compare manganese-based liposomes prepared by two different approaches wherein a
      manganese ion was entrapped within the internal aqueous space of the vesicles or
      into the bilayer surface via membrane bound complexes. METHODS: Small unilamellar
      liposomes (SUVs) were prepared entrapping manganese chloride. Alkylated complexes
      of manganese were prepared and also incorporated into SUVs. The two different
      manganese-based liposomes were compared for in-vitro relaxivity, stability,
      toxicity, and in-vivo imaging in rats with liver tumors. RESULTS: Liposomes
      entrapping manganese had a concentration-dependent change in relaxivity that was
      maximal at a several-fold molar excess of phospholipid relative to manganese ion.
      Liposomes bearing membrane-bound complexes showed relaxivity inversely
      proportional to vesicle size. In-vivo imaging showed greater and more specific
      hepatic enhancement with manganese liposomes bearing alkylated complexes than
      those entrapping manganese ion. CONCLUSIONS: Correlation effects likely explain
      the increased relaxivity of manganese entrapped in phospholipid vesicles. Greater
      efficacy, however, is afforded by liposomes bearing alkylated complexes.

PMID- 8262750
TI  - Large-tip-angle spin-echo imaging. Theory and applications.
AB  - RATIONALE AND OBJECTIVES: Tissue contrast phenomenology was investigated
      analytically and clinically for a class of magnetic resonance (MR) pulse
      sequences we call large-tip-angle (LTA) spin-echo (SE) imaging. In comparison to
      traditional SE sequences (denoted 90 degrees-180 degrees-echo), the LTA sequence
      is of the form alpha degrees-180 degrees-echo, where 90 degrees < alpha < 180
      degrees. Theoretical analysis shows that appropriately designed LTA sequences can
      selectively boost the MR signal by 10%-150% in substances whose spin lattice (T1)
      relaxation values equal or exceed the sequence repetition time (TR). This unique
      contrast behavior potentially allows one to reduce TR (and hence imaging time) by
      30% to 50% while maintaining constant T2-weighted contrast or contrast-to-noise
      within an image. METHODS: Preliminary clinical testing of LTA sequences was
      performed in 60 patients with a wide range of cranial, spinal, musculoskeletal,
      and abdominal pathologies. Large-tip-angle images (1,500/80/130 degrees) were
      blindly and prospectively compared to conventional (2,600/80/90 degrees) SE
      images. RESULTS: Principal diagnoses were concordant between the readers in all
      cases, although minor variances in detail features were noted in 6 (10%) of 60
      cases. Large-tip-angle sequences revealed small cystic areas in two cerebral
      neoplasms and in a herniated disk which were not apparent on the standard SE
      images. However, the LTA images were rated to be "noisier" by visual assessment
      in 43 of 60 cases, the exception being for abdominal examinations, where
      respiratory and peristaltic artifacts were judged more severe on the standard SE
      sequences. CONCLUSIONS: Large-tip-angle SE imaging is an interesting technique
      capable of improving image contrast and signal from lesions with long T1 values
      when the sequence repetition time (TR) is short.

PMID- 8262751
TI  - Roentgen and the "new light"--Roentgen's moment of discovery. Part 3: The
      genealogy of Roentgen's barium platinocyanide screen.

PMID- 8262752
TI  - On the validity of the continuous and discrete confidence rating scales in
      receiver operating characteristic studies.

PMID- 8262753
TI  - Evaluation of medical students in radiology. Written testing using uncued
      multiple-choice questions.
AB  - RATIONALE AND OBJECTIVES: Evaluation of uncued multiple-choice questions (UMCQ)
      was compared with traditional multiple-choice questions (MCQ) for assessing
      medical student performance during radiology electives. Methods for analyzing and
      improving the quality of UMCQ examinations are described. METHODS: The authors
      compared the performance of radiology medical students on similarly constructed
      MCQ and UMCQ tests. For the UMCQ examination, the reliability (coefficient
      alpha), standard error of measurement, item difficulty index, and corrected item
      to-total test coefficient (point biserial correlation) were analyzed. RESULTS:
      Students' level of performance was lower on UMCQs (mean percent correct score =
      68.9 +/- 10.2 standard deviation [SD]) than on MCQs (mean percent correct score =
      75.6 +/- 12.4 SD). Coefficient alpha for the UMCQ format was .7690 (standard
      error of measurement mean = 4.89%). Analysis of the item difficulty index and
      point biserial correlation for each test item provided information for improving
      the quality of the UMCQ examination. CONCLUSIONS: Because the UMCQ measures
      students' abilities to recall critical information without providing cues, this
      format can be used to overcome some of the limitations of conventional MCQs. With
      simple computerization, analysis of UMCQ testing instruments provides important
      feedback to both the examinees and the examiner.

PMID- 8262754
TI  - Comparison of a videodisc system with a conventional film file for medical
      student teaching.
AB  - PURPOSE: The authors assessed the effectiveness of a videodisc film file compared
      with a conventional film file for teaching radiology to medical students.
      METHODS: Fourth-year medical students (N = 134) studied 116 cases selected from
      the American College of Radiology Learning File. Half the students studied 58
      skeletal cases using conventional films and half studied the same cases on a
      videodisc system. Student groups were then switched and those who studied
      skeletal cases on films studied 58 chest cases on videodisc and vice versa.
      Students received the same skeletal and chest tests and completed a
      questionnaire. RESULTS: For both skeletal and chest radiology, students studying
      films scored minimally higher than students using the videodisc. Students rated
      films superior to the videodisc for amount learned, convenience of use, and
      ability to detect lesions. CONCLUSIONS: Conventional film and videodisc methods
      resulted in similar levels of learning; however, students perceived conventional
      films to be a superior learning experience.

PMID- 8262755
TI  - Two-month headache in a nine-year-old boy.

PMID- 8262756
TI  - Multiple primary carcinomas of the upper aerodigestive tract.
AB  - Multiple primary squamous cell carcinomas in the upper aerodigestive tract are
      well described but rare. To be recognised as distinct primary tumours, such
      malignancies must fulfil a number of anatomical and histological criteria as
      defined by Warren and Gates. Classification is based on the temporal sequence of
      tumour diagnosis into three groups; simultaneous, synchronous and metachronous.
      Second and subsequent primary tumours may escape early detection if not actively
      searched for. We present a very unusual case of three synchronous tumours in the
      oral cavity and oropharynx. The literature is reviewed emphasising the importance
      of thorough investigation of the entire upper aerodigestive tract in patients
      with a squamous cell carcinoma in this region. Recommendations regarding follow
      up are also discussed.

PMID- 8262757
TI  - In situ ESWL for ureteric calculi: the optimum treatment?
AB  - In situ ESWL for ureteric calculi is associated with good stone clearance rates
      but is it without significant morbidity? A review of 189 patients with single
      ureteric calculi (150 upper ureter, 39 lower ureter calculi) revealed an 89%
      stone clearance for upper ureteral calculi and 80% stone clearance for lower
      ureteral calculi. However 11% of patients with upper ureteral calculi and 20% of
      patients with lower ureteral calculi required additional intervention for
      complications or failed treatment. In situ ESWL may not be the optimum therapy
      for all ureteric calculi especially those in the lower ureter.

PMID- 8262758
TI  - A new technique for measuring lower oesophageal sphincter competence in patients.
AB  - Oesophageal sphincter measurements were carried out on 80 patients using the
      stationary pull through technique; Normals (n = 21), Nutcracker (n = 12),
      Refluxers (n = 21), and Barrett's (n = 26). Sphincter pressure (LOSP), abdominal
      length of sphincter, and overall sphincter length were measured. The Sphincter
      Function Index (SFI) was calculated as the product of sphincter pressure and
      percentage sphincter length (AL) exposed to abdominal pressure. Patients also had
      routine endoscopy and 24 hour pHmetry. SFI values discriminated between all four
      groups. LOSP was significantly different for Barrett's (p < 0.01) and Nutcracker
      (p < 0.01) compared to normals. AL was significant for Refluxers (p < 0.001) and
      Barrett's (p < 0.001) compared to normals. SFI gives better discrimination than
      LOSP or AL alone and may be useful in evaluating the response to treatment.

PMID- 8262759
TI  - Endoscopic balloon sphincteroplasty for benign papillary stenosis--an alternative
      to surgical or endoscopic papillotomy?
AB  - Benign papillary stenosis is an uncommon but well recognised cause of recurrent
      biliary pain usually in post-cholecystectomy patients characterised by biliary
      dilatation without bile duct calculi or malignancy. Endoscopic or surgical
      papillotomy is the recommended treatment but may be associated with a higher
      complication rate than when performed for bile duct stones. We report 2 cases of
      papillary stenosis treated by endoscopic balloon dilatation or
      "sphincteroplasty", as a less traumatic intervention which improved biliary
      drainage and provided symptomatic relief. Our preliminary experience suggests
      more widespread evaluation of balloon sphincteroplasty should be considered for
      papillary stenosis.

PMID- 8262760
TI  - Height, body weight, skinfold thickness and endurance fitness of children
      attending national schools in Ireland.
AB  - Height, body weight, the thickness of triceps, biceps, subscapular and supra
      iliac skinfolds and the six-minute run-walk test of aerobic endurance were
      measured on 1163 National school children between the ages of 7 and 13, who were
      attending rural or urban schools in counties Cork, Galway, Limerick, Mayo,
      Waterford and Wexford. Height, weight and the sum of triceps and subscapular
      skinfolds were compared with 11 to 13 year-olds from Northern Ireland, for whom
      the same data is available. Endurance scores were compared with international
      norms. Although of the same height as other European children, the subjects were
      heavier and had higher skinfold thicknesses. Aerobic endurance scores averaged
      about 80% of international norms.

PMID- 8262761
TI  - Purification, kinetic properties and primary structure of bovine erythrocyte
      acylphosphatase.
AB  - An erythrocyte isoenzyme of acylphosphatase was purified from bovine red cells.
      The protein was characterized as regards the kinetic parameters and amino acid
      sequence. A simple and rapid sequencing strategy, based on a few experiments, was
      used for reconstructing the primary structure of the enzyme, since the
      purification procedure gave a very low yield. The length of the polypeptide chain
      is 100 residues. Comparison with the analogous human isoenzyme indicates that the
      primary structure is about 90% conserved. The presence of two additional residues
      at the acetylated N-terminus confirms the hypervariability for this region found
      in other acylphosphatases.

PMID- 8262762
TI  - Minds and hearts. Priorities in mental health services.

PMID- 8262763
TI  - Guided by intimates.

PMID- 8262764
TI  - Washington State's no CPR program.

PMID- 8262765
TI  - The constitution and hastening inevitable death.
AB  - The due process clause of the Fourteenth Amendment protects the right of
      terminally ill persons to hasten their inevitable death. In prohibiting
      physicians from prescribing lethal medications by which such patients might
      hasten death, Michigan's ban on "assisted suicide" unconstitutionally imposes an
      "undue burden" on the exercise of that right.

PMID- 8262766
TI  - Facts, values, and expert testimony.

PMID- 8262767
TI  - For the benefit of all.

PMID- 8262768
TI  - "Ethics and clinical research" revisited. A tribute to Henry K. Beecher.
AB  - The doctrine of informed consent, borrowed from the law of torts, cannot be
      readily transplanted into therapeutic settings. The broader, as yet unrealized,
      idea of informed consent, which suggests that parties must make decisions
      jointly, should guide interactions between physicians and patients or
      investigators and subjects.

PMID- 8262769
TI  - Let's talk.

PMID- 8262770
TI  - Who wants to know?

PMID- 8262771
TI  - Truth lies somewhere, if we knew but where.

PMID- 8262772
TI  - Decisions at the end of life. Guided by communities of patients.
AB  - To guide treatment decisions for incompetent patients who have no advance
      directives, health care institutions should look to the preferences of their own
      communities of patients. That is the best way to ensure that incompetent
      patients' wishes will be followed.

PMID- 8262773
TI  - Salmonellosis in Hawaii: 1987 to 1990.
AB  - After an overview of salmonellosis, its epidemiology is described and techniques
      are discussed by which the disease could be brought under control. A review is
      made of all salmonellosis cases reported to the Department of Health Epidemiology
      Branch for calendar years 1987 to 1990. This data is compared with national and
      state laboratory data. Reports received by the Epidemiology Branch often lack
      sufficient information; this accounts for the sizable "unknown" entries. This
      frustrates a person's understanding of a more accurate incidence of the disease.

PMID- 8262774
TI  - One Rx for solo survival.
AB  - The Clinton administration's prescription for the "health care crisis" that was a
      hot campaign topic will be forthcoming. Mrs. Clinton is not backing away from the
      100-day deadline set by the President. Hillary has already begun to focus on some
      of her big hits, if one can believe the media reports about her comments related
      to drug companies. The months ahead will be crucial for solo and independent
      physicians and should be used by them to prepare for a change in how they
      practice medicine. The following article suggests one area to which they may
      choose to direct their energies.

PMID- 8262775
TI  - In pursuit of excellence: a model of collaboration for nurses at Hawaii State
      Hospital.
AB  - In 1989 the Hawaii Medical Journal devoted an issue to the status of mental
      health in Hawaii and mental health leaders in the State criticized the lack of
      involvement by the University of Hawaii. This paper is written in response to the
      challenge and will discuss a dynamic model based on collaboration between the
      Hawaii State Hospital (HSH) and the School of Nursing of the University of Hawaii
      (SoN), that was implemented in September 1990. Since the publication of Magnet
      Hospitals. Attraction and Retention of Professional Nurses there has been much
      interest by service organizations in defining the factors that build excellence.

PMID- 8262776
TI  - HMSA.

PMID- 8262777
TI  - Stroke and traumatic brain injury (ma'i ulu) in Amerika Samoa.
AB  - This paper discusses the annual incidence of stroke and traumatic brain injury
      (TBI) in American Samoa. Findings are based on data collected from the medical
      records at LBJ Tropical Medical Center in Amerika Samoa from June 1, 1989 to May
      31, 1990. A review of these medical records revealed that stroke and TBI were
      prevalent among the residents of Amerika Samoa during the time period sampled.
      Health and cultural factors which contribute to the occurrence of stroke and TBI
      in Amerika Samoa and recommendations for further investigation and prevention of
      stroke and TBI in that country are discussed.

PMID- 8262778
TI  - Blood lead levels among children in Hawaii.
AB  - The objectives of this study were to estimate blood lead levels of children under
      6 years of age in the State of Hawaii, to identify high-risk populations, and to
      decide what kind of blood lead screening program is needed in Hawaii. Children
      from Oahu and Maui were recruited in medical care facilities and 6 preschools.
      Informed consent for a blood lead test was obtained from the parents. A
      questionnaire was administered whenever possible; participation/response rates
      were quite low, varying between 15% and 50%. The mean blood lead level for the
      389 study participants was 4.5 micrograms/dL. Twelve children (3% of children
      tested) had a level above 9 micrograms/dL. No child was found to have a level
      above 14 micrograms/dL. Blood lead levels varied by age, geographic area,
      occupational factors, laboratory that performed the analysis, and type of
      phlebotomy (capillary versus venous) but not by sex, ethnicity or age of home.
      Follow-up investigations in the 12 homes of the children with levels above
      9/lg/dL were performed and in 3 homes a possible source of lead exposure was
      found.

PMID- 8262779
TI  - A population-based survey of headache and migraine in 22,809 adults.
AB  - A population-based epidemiological study of the prevalence of headache in a
      sample of 24,682 adults was carried out in Finland. Enquiries were made
      concerning the frequency of headache, migraine and characteristics of headache
      attacks in a questionnaire survey in 1981. Headache was classified as migraine,
      and headache without migrainous features. Possible somatic causes of headache
      were excluded by record-linkage with three nation-wide medical registries. The
      prevalence of both headache types depended on age and gender. Among women the
      overall prevalence of migraine was 10.1% with a maximum of 11.5% in the 40-49 age
      group. The prevalence rate among men was 2.5% and the female/male gender ratio
      was 4.0. Women with migraine had an average of 52.5 headache occasions during a
      year and men with migraine 61 headache occasions per year. At the individual
      level, headache without migrainous features was least invalidating. There were
      only 16.5 headache occasions a year among women and 11.5 among men. However, from
      a population perspective headache without migrainous features accounted for 46.5%
      of all headache occasions among women and for 60.8% among men. Thus, from the
      public health view-point, studies of "non-clinical" headache, e.g. headache
      without migrainous features should be emphasized.

PMID- 8262780
TI  - Brain potential differences related to spatial attention in migraineurs with and
      without aura symptoms support supposed differences in activation.
AB  - It is to be expected that differences in electrical activity of the brain between
      migraine patients with aura and those without aura can only be revealed by
      stimuli that provoke visual spatial processing, i.e. stimuli that trigger so
      called endogenous Visual Evoked Potential (VEP) activity. This is not the case
      for the flashes and checkerboard reversals. Those stimuli elicited exogenous
      activity only. During and between attacks the blood flow of migraineurs with aura
      changes in the posterior cerebral part of the brain, which is assumed to be
      specialized in the processing of spatial aspects of visual stimuli. Reaction
      times (RTs), early and late Event Related Potential (ERP) differences were
      compared at 12 scalp positions for two groups of migraineurs (with and without
      aura) and a control group. They had to perform a passive attention task,
      checkerboard reversals, and an active attention task, where attention was either
      divided into or focussed at spatial locations. In agreement with many studies on
      migraine, checkerboard stimuli did not differ on any early components. However,
      RTs were faster for migraineurs with aura and their early components were
      different when stimuli were highly attended. This is probably because these
      stimuli can relatively easily trigger cortical activity due to an over activated
      central mechanism and an enhanced level of attention.

PMID- 8262781
TI  - Migraine in patients with stroke and antiphospholipid antibodies.
AB  - The association between migraine and antibodies against antiphospholipids is
      controversial. We investigated the prevalence and the clinical feature of
      migraine in patients with ischemic stroke and antiphospholipid antibodies. Data
      were obtained from the medical records of 162 consecutive patients with ischemic
      stroke over a 2-year period. Ten patients with antiphospholipid antibodies were
      prospectively identified. A history of migraine was present in 6 of these
      patients and in only 5 of the 152 patients with negative results for
      antiphospholipid antibodies (chi-square = 47.68; P < .0001). In the former,
      migraine had been for a long time the only clinical problem before the occurrence
      of the ischemic stroke. These findings suggest that migraine is frequent and can
      be an early and a prominent symptom in the antiphospholipid antibodies syndrome.
      Further studies are needed to fully elucidate the association of migraine and
      antiphospholipid antibodies. A better knowledge of this association could allow
      an early identification of patients at high risk of stroke.

PMID- 8262782
TI  - The prevalence of headache and migraine in atopic children: an epidemiological
      study in general practice.
AB  - The lifetime prevalence of headache and migraine was assessed in an unselected
      sample of atopic (asthma, eczema or rhinitis) children in a general practice
      population of known socio-economic and age/sex composition. Maternal migraine was
      also recorded. The prevalence of both headache and migraine was significantly and
      proportionally higher in children with atopic disorders compared to those
      without. Childhood migraine was associated with atopy and the association was
      strongest with rhinitis. Rhinitis in children was associated with maternal
      migraine. A history of atopy (especially rhinitis) supports the diagnosis of
      migraine in young children with paroxysmal headaches.

PMID- 8262783
TI  - Subcutaneous sumatriptan in the acute treatment of migraine in patients using
      dihydroergotamine as prophylaxis. French Migraine Network Bordeaux-Lyon-Grenoble.
AB  - The efficacy of sumatriptan, a 5-HT1 receptor agonist, in patients with migraine
      attacks occurring despite prophylactic treatment with oral dihydroergotamine, was
      assessed in a double-blind placebo-controlled study involving 76 patients. Thirty
      seven patients were treated with a subcutaneous injection of 6 mg sumatriptan
      self-administered with an auto-injector and 39 with placebo given by the same
      route. Patients having inadequate relief were allowed to use a second injection
      of test medication 1 hour later and rescue treatment between 2 hours and 24 hours
      after the first dose. Headache relief was achieved within 2 hours after
      sumatriptan in 26 patients (70%) compared to 8 patients (21%) in the placebo
      group (P < 0.0001). Of these patients, 19 (51%) and 3 (8%) were, respectively,
      pain free at this time. A second injection of sumatriptan was used by 8 (22%)
      patients compared to 30 (77%) patients in the placebo group (P < 0.0001), whereas
      rescue medication was used respectively by 13 (35%) and 22 (58%) patients (P <
      0.024). The adverse event profile of sumatriptan was not affected by the
      concomitant use of dihydroergotamine and side-effects were all minor and
      transient. Patient satisfaction was significantly higher in the sumatriptan group
      (75%) compared to patient satisfaction with placebo (16%). These results show
      that the high efficacy rate of subcutaneous sumatriptan and its safety profile
      remain unchanged in migraine patients receiving oral dihydroergotamine as
      prophylaxis.

PMID- 8262784
TI  - Polypharmacy in a headache centre population.
AB  - In this paper we report the prevalence of self-medication and polypharmacy in our
      patient population at the John R. Graham Headache Centre at the Faulkner
      Hospital, Boston. One hundred fifty patients were interviewed when they called
      the Headache Centre and spoke to a triage nurse. A significantly higher number of
      women than men called in for triage counselling. Sixty-nine percent of the
      patients reported taking non-Headache Centre medications, either prescribed or
      over the counter (OTC); 39% of the patients took pain medications. Thirty-one
      different medications were named by patients for a mix of diagnoses.

PMID- 8262785
TI  - Italian experience of electromyographic-biofeedback treatment of episodic common
      migraine: preliminary results.
AB  - Electromyographic biofeedback is commonly used successfully to treat tension-type
      headache, while thermal biofeedback is considered the best behavioral therapy for
      migraine. Ten female patients with episodic common migraine (age 20-35 years, age
      of disease onset 16.2 +/- 5.1 years, illness duration 13.6 +/- 10.7 years) were
      treated by 16 twice-weekly electromyographic biofeedback and relaxation training
      sessions with breathing exercises. Follow-up sessions were held 1,3,6 and 12
      months after the end of treatment. A significant decrease in migraine episodes
      was noted after therapy. More importantly, pain episodes continued to decline up
      to the last follow-up 12 months later. Electromyographic activity was within the
      normal range throughout treatment and follow-up, and there was no relationship
      between electromyographic activity and pain index. It is concluded that the
      results, particularly after a year's follow-up, are encouraging for the use of
      this technique to treat migraine. However, the behavioral changes and increased
      well-being did not correlate with muscular tension. Control of breathing,
      peripheral temperature and muscle activity are probably important common factors
      mediating learned ability to influence sympathetic activity; it is probably the
      latter which leads to reduced pain in migraine patients.

PMID- 8262786
TI  - Analgesic use and chronic renal disease in patients with headache.
AB  - The pattern of analgesic use, abuse and incidence of analgesic-associated
      nephropathy in 79 patients with chronic headache was studied. Sixty-eight of
      these patients had migraine. Most patients had consumed a combination of
      analgesics (81%) while 19% had taken single analgesics for their headache.
      Nonsteroidal anti-inflammatory drugs were the most commonly used analgesics
      (96.2%) followed by paracetamol (70.9%) and aspirin, phenacetin and caffeine
      compounds (5.1%). Mefenamic acid was the commonest nonsteroidal anti-inflammatory
      drug consumed (97.4%). Analgesic abuse which was defined as a minimum total of 1
      kg of analgesics such as paracetamol or aspirin, phenacetin and caffeine
      compounds or 400 capsules/tablets of nonsteroidal anti-inflammatory drugs was
      noted in 65 patients. Nonsteroidal anti-inflammatory drugs were the most commonly
      abused analgesics (89.2%) followed by paracetamol (38.5%). Forty-five of the 65
      analgesic abusers had an intravenous urogram or ultrasound performed and renal
      papillary necrosis was documented in one patient. Three (4.6%) of the analgesic
      abusers had mildly raised serum creatinine levels. Mild proteinuria of less than
      1 gm/litre was present in 27.7% of abusers. In conclusion, although analgesic use
      and abuse is common in patients with chronic headache, the short term incidence
      of analgesic-associated nephropathy (2.2%) and renal impairment (4.6%) was low.
      Prolonged observations will be necessary to ascertain the safety of these drugs
      for long term use.

PMID- 8262787
TI  - A contrast enhanced lesion of the III nerve on MR of a patient with
      ophthalmoplegic migraine as evidence for a Tolosa-Hunt syndrome.
AB  - A 23-year-old female with a six year history of migraine without aura twice
      developed a nearly complete internal and external III nerve paresis ipsilateral
      to her headache, two days after the onset of migraineous headache. An MR scan
      performed one week after the second episode showed a contrast enhanced lesion of
      the prepontine III nerve, where it enters the cavernous sinus on the left side.
      The headache, as well as the paresis ameliorated spontaneously. We suggest this
      is a further well documented case of "ophthalmoplegic migraine" which might
      reflect Tolosa-Hunt syndrome.

PMID- 8262788
TI  - Bilateral Horner's syndrome in cluster type headaches.
AB  - A patient with cluster type headaches demonstrated bilateral and alternating
      ocular sympathetic dysfunction during a spontaneous as well as a nitroglycerin
      induced attack. Biochemical evaluation revealed postganglionic pupillary
      dysfunction on the symptomatic side and preganglionic pupillary dysfunction
      contralaterally. These findings defy a simple explanation regarding a central or
      peripheral origin of the oculocephalic sympathetic dysfunction.

PMID- 8262789
TI  - Headache caused by a single lesion of multiple sclerosis in the periaqueductal
      gray area.
AB  - We report a severe acute headache that occurred in conjunction with a solitary
      fresh lesion of multiple sclerosis in the periaqueductal gray region of a 16-year
      old girl. This unique natural event supports the recent proposition, based on
      observations of patients with implanted electrodes, that perturbations of the
      periaqueductal gray region can produce headache. It also suggests that headaches
      accompanying attacks of multiple sclerosis are due to disturbances in particular
      regions of the brain.

PMID- 8262790
TI  - Nonpharmacological treatment of headache.

PMID- 8262791
TI  - Towards a functional model of chronic headaches: investigation of antecedents and
      consequences.
AB  - The traditional approach to classifying headache based on symptoms and assumed
      mechanisms is criticized as having limited utility when applied to tension-type
      headache and migraine. The study reported here was designed to explore an
      alternative method of conceptualizing chronic headaches based on functional
      characteristics or controlling variables. One hundred and ninety nine chronic
      headache sufferers completed questionnaires which enquired about the antecedents
      and consequences of their headaches. An attempt to build a categorical model
      driven by functional characteristics using cluster analysis was unsuccessful but
      a subsequent attempt to construct a dimensional model using factor analysis
      proved more successful. This approach led to the emergence of five antecedent
      dimensions and six consequences dimensions (three pertaining to the responses of
      sufferers and three to the reactions of significant others) which were readily
      identifiable. The functional dimensions were significantly related to traditional
      diagnostic categories but at a low level. Three functional dimensions predicted
      response to psychological treatment.

PMID- 8262792
TI  - Office-based treatment of acute migraine with dihydroergotamine mesylate.
AB  - The Regional Migraine Field Trial assessed the efficacy and safety of
      dihydroergotamine mesylate (D.H.E. 45) for migraine in the office setting.
      Patients were admitted to the study provided they met the International Headache
      Society definition of migraine with or without aura. Thirty-eight neurologists
      enrolled 311 patients (274 women and 37 men) between the ages of 13 and 70 years
      in this open-design study. Ninety-five percent of the patients had moderate or
      severe headache pain at entry, and 62% had nausea. All patients received a single
      intramuscular injection of D.H.E. 45 1 mg. A second intramuscular injection of 1
      mg was given 60 minutes after the first injection, if needed. An antiemetic was
      administered concomitantly with D.H.E. 45, if needed. Rescue therapy was given at
      the investigators' discretion. Efficacy was judged by the relief of pain,
      patients' ability to function, need for a second injection, need for rescue
      medication, and need for an antiemetic. At 30 and 60 minutes, 46% and 72% of
      patients had only mild or no head pain, respectively. At 24 hours, 77% of all
      patients had mild or no head pain. D.H.E. 45 also improved functional ability. At
      30 and 60 minutes, 58% and 75% of patients had only mild or no disability,
      respectively. At 24 hours, 81% had mild or no impairment. Nausea was present in
      62% of patients at the outset, 40% of patients at 30 minutes, and 30% at 60
      minutes. An antiemetic was given to 43% of patients at the outset. The presence
      of nausea was similar whether or not patients received an antiemetic.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8262793
TI  - Cluster headache: the ventilatory response to transient hypoxia with pure
      nitrogen.
AB  - To determine whether the carotid body plays a pathogenetic role in cluster
      headache, 20 cluster headache patients have been studied. Of these, 11 patients
      were in the interparoxysmal cluster phase, and 9 were in remission. Comparison
      was made with healthy subjects matched for sex, age, and smoking habits.
      Transient hypoxia was induced by inhalation of 1-8 breaths of 100% nitrogen (N2),
      until the arterial oxygen saturation (SaO2) decreased to around 80%. Changes in
      ventilation (tidal volume, inspiratory minute ventilation (VI), and end-tidal
      PCO2 (PETCO2)), were analyzed breath-by-breath. Under basal conditions, cluster
      headache patients had a slightly higher SaO2 and VI when compared to controls.
      PETCO2 was significantly lower (P < 0.05) during the cluster period as measured
      by Wilcoxon signed rank test for paired data, and during remission, according to
      the Student's paired t-test, in comparison with controls. After exposure to N2,
      no significant difference was found in the rate of reduction of SaO2 between any
      of the groups. A higher absolute increase in VI, but a relative (%) decrease in
      VI at moderate hypoxia were measured, the differences between patients and
      controls being on the border of the level of significance. Chemoreceptor
      sensitivity of the carotid body, expressed as the slope of a regression curve
      obtained by plotting the increase in VI against the reduction in SaO2, showed no
      statistical difference between the groups. The results do not support the
      hypothesis of a pathogenetic role for the carotid body in cluster headache.

PMID- 8262794
TI  - The role of chemoreceptor activity and oxyhemoglobin desaturation in cluster
      headache.

PMID- 8262795
TI  - Hemicrania continua and symptomatic medication overuse.
AB  - Hemicrania continua (HC) is a rare, strictly unilateral, nonparoxysmal headache
      disorder characterized by its absolute responsiveness to indomethacin. The pain
      is usually moderate in intensity and frequently associated with a superimposed
      "jabs and jolts" headache. We report two cases of HC which presented as chronic
      daily headache (CDH) with abortive medication overuse. CDH can be due to
      transformed migraine (TM), new daily persistent headache (NDPH), chronic tension
      type headache, and HC. All can be unilateral, and all can be associated with
      medication overuse. Our two cases meet the criteria for HC based on indomethacin
      responsiveness. One meets the criteria for TM, the other NDPH. Is HC a distinct
      disorder, or a subset of these other disorders? CDH with medication overuse
      includes in its differential diagnosis HC.

PMID- 8262796
TI  - Diagnoses and symptom patterns in children presenting to a pediatric headache
      clinic.
AB  - The diagnosis of migraine headache in children and adolescents is complex and not
      well understood. This study was conducted to compare diagnostic rates, using
      various criteria for pediatric migraine, and specific symptom characteristics in
      a sample of children referred for care to a specialized pediatric headache
      clinic. A structured interview was used at the patient's initial assessment visit
      to elicit symptom patterns and therapies attempted for headache. Clinical
      diagnoses were based on consensus agreement reached by a multidisciplinary team.
      Statistically derived diagnostic rates based on International Headache Society
      (IHS), Prensky, Vahlquist and our own criteria were significantly lower than
      clinical diagnostic rates. IHS diagnostic rates were differentially distributed
      as a function of race, but no other effects were found for demographic variables
      on diagnostic rates. Specific symptom patterns, however, varied as a function of
      race, gender and age of the child. The results underscore the need for
      comprehensive, developmentally based models of the evolution of migraine headache
      as a foundation for future research and the further development of clinically
      sensitive diagnostic criteria for pediatric migraine.

PMID- 8262797
TI  - A note on migraineurs' postures during attacks.

PMID- 8262798
TI  - Embolization of a tentorial dural arterio-venous fistula presenting as atypical
      trigeminal neuralgia.
AB  - A patient with a tentorial dural AV fistula causing atypical trigeminal neuralgia
      (TN) successfully treated by embolization is reported. The patient developed
      persisting throbbing facial pain in the distribution of the second and third
      division of the right trigeminal nerve (V2, V3) after a history of typical
      neuralgia for one year, preceded by a two month spell of TN 6 years previously
      and accompanied by right-sided pulsatile tinnitus for 10 years. The patient's
      mother, brother and sister were also said to be affected by typical trigeminal
      neuralgia. A right-sided dilated vein of Rosenthal due to a dural AV fistula fed
      by branches of the meningeal, occipital and meningo-hypophyseal trunk of the
      internal carotid artery was thought to cause trigeminal nerve compression.
      Complete resolution of symptoms after partial intra-arterial embolization of the
      main feeding arteries with N-butyroacrylate is described.

PMID- 8262799
TI  - Uncommon EEG pattern in an 8-year-old boy with recurrent migraine aura without
      headache.
AB  - A case of an 8-year-old boy with recurrent migraine auras without headache,
      precipitated by minor head trauma, is reported. Aura was characterized, besides
      other brain-stem signs, by confusional state. An uncommon electroencephalographic
      pattern recorded during the episodes, characterized by diffuse continuous beta
      activity, is described. Recognition of this finding may prevent an inappropriate
      diagnosis of drugs ingestion.

PMID- 8262800
TI  - Cluster-tic syndrome and basilar artery ectasia: a case report.
AB  - A 54-year-old patient presented with two types of pain. The first was similar to
      trigeminal neuralgia and the second was similar to cluster headache. Clinical
      diagnosis was cluster-tic syndrome. Neuro-imaging studies disclosed an ectatic
      basilar artery. The significance of this finding is difficult to ascertain.

PMID- 8262801
TI  - Home care consumers speak out on quality.
AB  - Who should be the judge of quality care--the consumer or healthcare professional?
      Traditionally, healthcare providers have decided what services consumers should
      receive and how consumers' needs should be met. Current trends in healthcare
      delivery are changing this one-sided practice. Throughout the United States, to
      determine what constitutes quality care, accrediting bodies, insurers, consumer
      groups, providers, and governments are collecting and analyzing data on standards
      for clinical practice, patient outcomes, and perceptions of those receiving
      healthcare.

PMID- 8262802
TI  - Home care in a service station.
AB  - This article gives insight into the challenges facing the home health nurse of
      today. To maintain autonomy and meet the health needs of the patient in his or
      her home environment, the nurse must be creative, flexible, and often
      unconventional in his or her approach.

PMID- 8262803
TI  - Reaching for the ideal in home care.
AB  - Home care as delivered by agencies with Medicare as the primary source of
      reimbursement and by the Hospital Base Home Care programs in the Veteran's
      Administration system are described and compared. Physician-home care
      relationships are explored and team function is examined. Recommendations for the
      improvement in home care are made.

PMID- 8262804
TI  - Venous stasis ulcers: assessment and treatment in the home care setting.
AB  - This is a comprehensive article about assessment and treatment of venous stasis
      ulcers in the home. It includes information regarding the pathophysiology,
      assessment, treatment, follow-up care, and reimbursement considerations of venous
      stasis ulcers, and was written for the home health enterostomal therapy nurse and
      the home health nurse.

PMID- 8262805
TI  - Tri-State Home Health Council.

PMID- 8262807
TI  - Continuing our centennial of public health nursing.

PMID- 8262806
TI  - The tragic rabies death of an 11-year-old girl.

PMID- 8262808
TI  - Home health in rural Kenya.
AB  - Despite the many environmental and cultural differences, many similarities exist
      between home health nursing in Kenya and the United States. Family-focused care
      is the goal, with emphasis on education and prevention.

PMID- 8262809
TI  - Analgesics for the oncology patient.

PMID- 8262810
TI  - Competent, supervised, unlicensed personnel will contribute to high-quality, in
      home health care.
AB  - To provide high-quality healthcare services to all age groups in the 1990s, I
      believe that specific tasks can be delegated to qualified, competent, unlicensed
      personnel. In reality, many environmental and family factors mentioned earlier in
      this paper cannot be changed. But, the role and responsibilities of qualified,
      unlicensed caregivers can be expanded, given that the professional registered
      nurse retains the accountability for delegated tasks. This change has the
      potential to contribute to the well-being of the patients and to improve the
      overall quality of in-home healthcare in the 1990s.

PMID- 8262812
TI  - Past is prologue.

PMID- 8262811
TI  - Clinical documentation guidelines: Medicare reimbursement.

PMID- 8262813
TI  - Lesbian hospice patients.

PMID- 8262814
TI  - Sexual harassment.

PMID- 8262815
TI  - Dissociation of catecholamine and corticosterone responses to different types of
      stress in rats.
AB  - To examine hormonal response patterns to various stresses, urinary excretion of
      catecholamines and corticosterone was measured in spontaneously hypertensive rats
      (SHR) and Wistar-Kyoto normotensive rats (WKY) under the following conditions:
      immobilization, restriction to a small space, introduction of new rats, and noise
      exposure. In WKY rats, immobilization caused a marked increase in urinary
      corticosterone, adrenaline and noradrenaline and a decrease in dopamine
      excretion. Restriction to a small space induced a less pronounced but still
      obvious increase in adrenaline and corticosterone and a decrease in dopamine.
      When other rats were introduced into the animal room, the senior rats showed an
      increase in adrenaline alone, while noise exposure produced an increase in
      corticosterone alone. These findings suggest that while severe stress, such as
      immobilization, causes marked changes in all 4 hormones, relatively mild stress
      produces changes in one to three, not all, hormones, and that catecholamine and
      corticosteroid responses are dissociated in some forms of the mild stress. It is
      considered that neuroendocrine responses to stress vary according to both the
      type of stress and its intensity. In SHR rats, the hormone response to severe
      stress was greater than in WKY rats, and the response was somewhat less than in
      WKY rats when exposed to mild stress. These findings do not imply that stress
      induced hyperactivity of sympathetic adrenomedullary system participates in the
      development of hypertension in SHR rats.

PMID- 8262816
TI  - Effects of lead on electrophoretic mobility, membrane sialic acid, deformability
      and survival of rat erythrocytes.
AB  - The anemia frequently observed in lead poisoning is thought to result from the
      shortening of erythrocyte life span in combination with inhibition of hemoglobin
      synthesis. However, the exact mechanism by which lead shortens the life span of
      red blood cells (RBCs) remains unclear. In the present study, the effects of
      injected lead on electrophoretic mobility, membrane sialic acid content,
      deformability and survival of rat RBCs were investigated in order to clarify the
      relationships between them. As indices of lead exposure, RBC counts, hemoglobin
      (Hb) levels, hematocrits (Ht), mean corpuscular volume (MCV), mean corpuscular
      hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and blood lead
      (blood Pb) levels in the rats were also examined. Exposure to lead significantly
      decreased RBC counts, Hb levels, Ht, MCV and MCH. Similarly, exposure to lead
      significantly decreased the mobility, sialic acid content and deformability of
      rat RBCs. A shortening of erythrocyte survival time was also observed in the rats
      exposed to lead. It is speculated that decreases in membrane sialic acid content
      and deformability of RBCs induce a shortening of erythrocyte survival time in
      anemia caused by lead.

PMID- 8262817
TI  - Carcinogenicity of benzotrichloride administered to mice by gastric intubation.
AB  - Epidemiological studies suggest that benzotrichloride (BTC) is a human
      carcinogen. In the present study, BTC was tested to evaluate its ability to
      induce lung tumors as a result of systemic exposure. Administration of BTC by
      gastric intubation, 2.0-0.0315 microliters/mouse (4 doses), twice a week for 25
      weeks, in female ICR mice, produced forestomach tumors (squamous cell carcinoma
      and papilloma), lung tumors (adenocarcinoma and adenoma) and tumors of the
      hematopoietic system (thymic lymphosarcoma and lymphatic leukemia) with dose
      related response by 18 months. The present and previous studies indicate that the
      target organs of BTC carcinogenesis in mice are the local tissue which is
      primarily exposed, and the lung and hematopoietic tissue when BTC is administered
      systematically.

PMID- 8262818
TI  - Cardiac autonomic dysfunction in rotogravure printers exposed to toluene in
      relation to peripheral nerve conduction.
AB  - The autonomic nervous effects of toluene remain less clear. To clarify this
      neurotoxicity, ten rotogravure printers and the same number of age-matched
      unexposed controls were examined, by using the coefficient of variation in
      electrocardiographic R-R intervals (CVRR), the distribution of nerve conduction
      velocities (DCV) and the maximal motor and sensory nerve conduction velocities
      (MCV and SCV) in the median nerve. Also, the C-CVHF and C-CVLF (two component CVs
      of the CVRR reflecting parasympathetic and sympathetic activities, respectively)
      were computed from component spectral powers using autoregressive spectral and
      component analyses. These printers had been exposed to toluene (estimated
      exposure levels of toluene at 83 ppm) for 1-36 years. The CVRR and C-CVHF were
      significantly lower in the printers than in the controls. No significant
      difference between the printers and the controls was found in either any DCV
      parameters or the SCV in the forearm, except the MCV and the SCV in the palm. In
      the light of previous work on the brainstem/hippocampus damages due to toluene,
      these data suggest that toluene causes potential damages in the central autonomic
      nervous system, mainly parasympathetic hypoactivity.

PMID- 8262819
TI  - Application of the microwave acid digestion technique to the pyrophosphoric acid
      method for quantitative analysis of free silica in dust.
AB  - An accurate and simple procedure for determining the quantity of free silica in
      respirable dust samples by the pyrophosphoric acid method was achieved by
      employing a closed vessel dissolution technique using microwave heating.
      Dissolution conditions were optimized by using quartz particles less than 10
      microns in diameter as representative respirable-size free silica and potassium
      feldspar (K-feldspar) of the same size as the matrix. The technique enabled
      dissolution of 100 mg of K-feldspar by pyrophosphoric acid in 3 min. Quartz
      recovery was 97% under these conditions. The technique was also tested on
      mixtures of quartz and K-feldspar in various ratios with reproducible and
      accurate results. These data satisfy the requirements for analysis of small
      amounts of respirable dust samples in work environments.

PMID- 8262820
TI  - The role of radiation therapy in the treatment of acute lymphoblastic leukemia
      with lymphomatous presentation: a report from the Childrens Cancer Group.
AB  - PURPOSE: Childrens Cancer Group 123 was a trial of intensive multidrug
      chemotherapy as well as cranial irradiation and bulk disease irradiation in
      children with acute lymphoblastic leukemia with lymphomatous presentation (bulk
      disease and either T-cell phenotype, high white blood count, or absence of
      anemia), a poor prognostic group with an increased risk of central nervous system
      (CNS) and other extramedullary recurrence. METHODS AND MATERIALS: Three hundred
      eight patients without CNS disease were randomized among three regimens: A--BFM
      chemotherapy (designed for high risk ALL patients) with 1800 cGy cranial
      irradiation; B--LSA2L2 chemotherapy (designed for non-Hodgkins lymphoma patients)
      with 1800 cGy cranial irradiation and 1500 cGy to nonabdominal bulk disease; C-
      Reg B without cranial irradiation. All patients received intrathecal methotrexate
      throughout therapy. Radiation treatment records were reviewed. RESULTS: With a
      minimum 52-month follow-up, Regimen B and C patients had 5-year actuarial CNS
      relapses of 7% and 17% (p = 0.01) and event-free survivals of 53% and 39% (p =
      0.04). Patients with white blood count < 50,000/mm3 did not benefit from cranial
      irradiation. Regimen A patients had the same CNS relapse rate as Regimen B
      patients but an improved event-free survival. Regimen B and C patients with large
      mediastinal masses who received their assigned chest radiation had a lower event
      rate than those who did not (p = 0.06). Patients whose cranial fields did or did
      not encompass the entire meningeal surface had equivalent CNS relapse rates.
      CONCLUSION: Patients treated with LSA2L2 chemotherapy, a less than optimal
      regimen, benefited from cranial and mediastinal irradiation. Compliance with
      radiation volume guidelines was not essential for patients to receive the benefit
      of cranial irradiation.

PMID- 8262821
TI  - Is a surgical resection leaving positive margins of benefit to the patient with
      locally advanced squamous cell carcinoma of the head and neck: a comparative
      study using the intergroup study 0034 and the Radiation Therapy Oncology Group
      head and neck database.
AB  - PURPOSE: The purpose of this study was to determine whether or not for patients
      with squamous cell carcinomas of the head and neck, a surgical resection leaving
      positive margins followed by postoperative adjuvant therapy improves the outcome
      compared to a matched group of patients treated with definitive radiotherapy
      alone. METHODS AND MATERIALS: From January 1985 through January 1990 a consortium
      of national cooperative groups (Radiation Therapy Oncology Group, Cancer and
      Leukemia Group B, Eastern Cooperative Oncology Group, Northern California
      Oncology Group, Southeast Group, and Southwest Oncology Group) conducted a phase
      III clinical trial testing the efficacy of adjuvant chemotherapy for patients
      with resectable, squamous cell carcinomas of the head and neck. One hundred and
      nine patients were excluded from this study due to positive surgical margins.
      These patients have been followed prospectively with regards to local/regional
      tumor control, development of distant metastases, and survival. The postoperative
      treatment of these patients was not specified by the protocol but the majority of
      patients received postoperative radiotherapy +/- chemotherapy. These patients
      were compared with a matched group of patients from the Radiation Therapy
      Oncology Group head and neck database of patients treated with definitive
      radiotherapy alone using a standard fractionation schema. Matching parameters
      included primary tumor site, T-stage, N-stage, Karnofsky performance status, and
      age. RESULTS: Actuarial curves are presented for local/regional control and
      survival. At 4 years the local/regional control rate is 44% for the positive
      margin patients compared to 24% for the patients from the data base (p = 0.007).
      However, there is no significant difference between the survival curves (p =
      0.76) with respective median survivals being 18.1 months vs. 17.9 months and 4
      year survivals being 29% vs. 25%. CONCLUSION: While an incomplete excision
      followed by postoperative therapy does not seem to improve survival compared to
      treatment with radiotherapy alone, it appears to yield significantly better
      local/regional control. This would argue for its applicability in selected
      palliative settings. A follow-up, Phase III trial for patients with advanced
      tumors may be warranted to test traditional resectability criteria.

PMID- 8262822
TI  - Radiotherapy alone or combined with neck dissection for T1-T2 carcinoma of the
      pyriform sinus: an alternative to conservation surgery.
AB  - PURPOSE: We present our experience with irradiation alone or combined with neck
      dissection for AJCC T1-T2 pyriform sinus carcinoma and compare our results to
      those obtained with conservation surgery. METHODS AND MATERIALS: Seventy-three
      patients were treated between 1964 and 1990. All patients had a minimum of 2
      years of follow-up; no patient was lost to follow-up. RESULTS: The 5-year rates
      of local control and ultimate local control were, for Stage T1 (17 patients), 88%
      and 94%; and for Stage T2 (56 patients), 79% and 91%. Patients with T2 lesions
      had a significantly higher rate of local control after twice-daily, compared with
      once-daily, irradiation (p = .04). However, a multivariate analysis of various
      parameters revealed that none of the variables tested significantly influenced
      this end point: vocal cord mobility (p = .15), once- vs. twice-daily
      fractionation (p = .33), T1 vs. T2 (p = .32), apex invasion (p = .58), and
      pretreatment CT scan (p = .67). Local control with laryngeal voice preservation
      was obtained in 88% of patients with T1 cancers and 80% of those with T2 cancers.
      Ultimate control above the clavicles at 5 years according to AJCC stage was as
      follows: I and II, 100%; III, 78%; IVA, 75%; and IVB, 60%. The probability of
      cause-specific survival at 5 years was as follows: I and II, 100%; III, 83%; and
      IVA and IVB, 51%. Overall, nine patients (12%) developed severe complications,
      one of which was fatal. CONCLUSION: Compared with available data from series
      using conservation surgery, radiotherapy alone or followed by neck dissection
      results in similar rates of local control and survival with a significantly lower
      risk of fatal complications.

PMID- 8262823
TI  - Lhermitte's sign: incidence and treatment variables influencing risk after
      irradiation of the cervical spinal cord.
AB  - PURPOSE: Lhermitte's sign is a relatively infrequent sequela of irradiation of
      the cervical spinal cord. In this study, we sought to determine whether various
      treatment parameters influenced the likelihood of developing Lhermitte's sign.
      METHODS AND MATERIALS: Between October 1964 and December 1987, 2901 patients with
      malignancies of the upper respiratory tract were treated at the University of
      Florida. The dose of radiation to the cervical spinal cord was calculated for
      those patients who had a minimum 1-year follow-up. A total of 1112 patients who
      received a minimum of 3000 cGy to at least 2 cm of cervical spinal cord were
      included in this analysis. RESULTS: Forty patients (3.6%) developed Lhermitte's
      sign. The mean time to development of Lhermitte's sign after irradiation was 3
      months, and the mean duration of symptoms was 6 months. No patient with
      Lhermitte's sign developed transverse myelitis. Several variables were examined
      in a univariate analysis, including total dose to the cervical spinal cord,
      length of cervical spinal cord irradiated, dose per fraction, continuous-course
      compared with split-course radiotherapy, and once-daily compared with twice-daily
      irradiation. Only two variables proved to be significant. Six (8%) of 75 patients
      who received > or = 5000 cGy to the cervical spinal cord developed Lhermitte's
      sign compared with 34 (3.3%) of 1037 patients who received < 5000 cGy (p = .04).
      For patients treated with once-daily fractionation, 28 (3.4%) of 821 patients who
      received < 200 cGy per fraction developed Lhermitte's sign compared with 6 (10%)
      of 58 patients who received > or = 200 cGy (p = .02). CONCLUSION: An increased
      risk of developing Lhermitte's sign was demonstrated for patients who received
      either > or = 200 cGy per fraction (one fraction per day) or > or = 5000 cGy
      total dose to the cervical spinal cord.

PMID- 8262824
TI  - Pituitary adenomas: long-term results for radiotherapy alone and post-operative
      radiotherapy.
AB  - PURPOSE: Analysis of prognostic factors and long-term results of treatment of
      pituitary adenomas. METHODS AND MATERIALS: The study involved a retrospective
      review of outcome in a series of 268 patients with pituitary adenomas, treated at
      the Queensland Radium Institute from January 1962 to December 1986. The study
      population included 108 patients treated with radiotherapy alone and 160 patients
      treated by surgery and post-operative radiotherapy. In each group, univariate and
      multivariate analyses were conducted of possible prognostic factors including
      age, sex, performance status, tumor type, tumor extent, visual disturbance,
      radiotherapy dose, and field size. RESULTS: For radiotherapy alone, the 10-year
      progression-free survival rate was 60%, and overall tumor control was obtained in
      77%. Univariate analysis suggested that tumor type and radiotherapy field size
      were of prognostic significance. Multivariate analysis confirmed that
      Prolactinoma subtype and increasing radiotherapy field size were independently
      predictive of reduced progression-free survival. Long-term visual complications
      occurred in 1% of patients treated by radiotherapy alone. In patients treated by
      surgery and post-operative radiotherapy, the 10-year progression-free survival
      rate was 77%, and overall tumor control was achieved in 83%. Univariate analysis
      suggested that tumor type, completeness of surgical excision, and radiotherapy
      dose were predictive of outcome. However, on multivariate analysis, only the
      extent of surgical excision predicted prognosis independently. Long-term visual
      sequelae were noted in 3% of patients treated by surgery and post-operative
      radiotherapy. CONCLUSION: Both radiotherapy alone and post-operative radiotherapy
      are effective in long-term control of pituitary adenomas, and produce acceptably
      low complication rates.

PMID- 8262825
TI  - Age as a prognostic factor for breast and regional nodal recurrence following
      breast conserving surgery and irradiation in stage I and II breast cancer.
AB  - PURPOSE: To evaluate the association between age and breast/regional nodal
      relapse following breast conserving surgery and irradiation. METHODS AND
      MATERIALS: The results of treatment in 511 patients with 519 Stage I and II
      breast cancers treated at Mallinkrodt Institute of Radiology and affiliated
      hospitals between 1958 and 1988 were reviewed. RESULTS: Seventy women, of whom
      96% had axillary dissections, were 39 years of age or younger. These young
      patients were more likely to have chemotherapy (p < 0.0001), and tumor bed
      reexcision (p < 0.01), and less likely to have an undissected axilla (p < 0.01),
      or estrogen receptor positive tumor (p = 0.02) than the older women (> 40 years).
      Although breast recurrence tended to appear earlier in the younger patients (12%
      at 5 years for those < 40 years vs. 6% at 5 years for those older), by 7 years
      the breast failure rate for the two groups was the same (12%), p = 0.13. In the
      37 women 35 years of age or younger, the actuarial rate of breast recurrence was
      9% at 7 years. Compared to other series in the literature, in which cancers were
      grossly excised without regard to the microscopic margins of resection, and
      reexcision was not routinely performed, young women treated with breast
      conserving surgery and irradiation at our institution frequently underwent
      reexcision of the tumor bed (57%), and had negative pathologic margins of
      resection (75%). Regional nodal relapse was in general uncommon, and not seen
      with increased frequency in the youngest cohort. CONCLUSION: Our experience
      suggests that young age is not a contraindication to breast conserving surgery
      and irradiation. Although breast cancers in this cohort may have certain features
      rendering them prone to local failure, we believe this risk can be mitigated by
      appropriate patient selection and optimal surgical resection.

PMID- 8262826
TI  - Overall treatment time in advanced cervical carcinomas: a critical parameter in
      treatment outcome.
AB  - PURPOSE: To search for possible influence of overall treatment time on the
      clinical outcome of advanced cervical carcinomas treated with radiation alone.
      METHODS AND MATERIALS: Three hundred and eighty-six patients with Stage IIB and
      III cervical carcinomas treated with external radiation and intracavitary
      curietherapy between 1973 and 1983 were entered in the study. A multivariate
      analysis was carried out on data concerning these patients to determine whether
      overall treatment time was a prognostic factor. RESULTS: Overall treatment time
      and blood transfusions during treatment were the two most highly significant
      factors in the multivariate analysis. Loss of local control and overall survival,
      when treatment exceeded 52 days, was approximately 1% per day in both cases.
      CONCLUSION: These results suggest that overall treatment time might be a highly
      significant prognostic factor in the treatment outcome of advanced cervical
      carcinomas. Prospective randomized studies are strongly warranted to confirm this
      hypothesis.

PMID- 8262827
TI  - A randomized prospective trial of radiation therapy for AIDS-associated Kaposi's
      sarcoma.
AB  - PURPOSE: The optimal dose of radiation in the treatment of AIDS-associated
      Kaposi's sarcoma has been controversial based on previous nonrandomized
      retrospective studies. METHODS AND MATERIALS: Seventy-one cutaneous AIDS
      associated Kaposi's sarcoma lesions were randomly assigned to 1 of 3 radiation
      dose regimens--8 Gy in 1 fraction, 20 Gy in 10 fractions, and 40 Gy in 20
      fractions. Lesions were measured prior to and following treatment. Complete
      resolution of palpable tumor was considered a complete response, regardless of
      residual purple pigmentation. Reduction in palpable tumor to less than 50% of
      pretreatment area was considered an objective response. Less than 50% reduction
      in tumor size was considered a nonresponse. RESULTS: Complete response was higher
      (p = .04) with 40 Gy (83%) and 20 Gy (79%) than with 8 Gy (50%). Absence of
      residual purple pigmentation was greater (p = .005) with 40 Gy (43%) than with 20
      Gy (8%) or 8 Gy (8%). Lesion failure was lower (p = .03) with 40 Gy (52%) than
      with 20 Gy (67%) or 8 Gy (88%). Median time to failure was 43 weeks with 40 Gy,
      26 weeks with 20 Gy, and 13 weeks with 8 Gy (p = .003). CONCLUSION: Fractionated
      radiotherapy to higher total doses resulted in improved response and control of
      cutaneous Kaposi's sarcoma. This dose-dependence should be considered in
      determining the optimal radiotherapeutic regimen for individual patients treated
      for epidemic Kaposi's sarcoma.

PMID- 8262828
TI  - Intraoperative radiotherapy for esophageal carcinoma--significance of IORT dose
      for the incidence of fatal tracheal complication.
AB  - PURPOSE: The feasibility of intraoperative radiotherapy (IORT) combined with
      modified regional lymphatic dissection (plus esophagectomy) for advanced
      esophageal carcinoma was tested. The quality of life in the patients was expected
      to improve by modified surgery, securing a good local control by additional IORT.
      METHODS AND MATERIALS: Total esophagectomy plus modified three-regional lymphatic
      dissection with upper mediastinal IORT followed by postoperative external beam
      irradiation was systematically given to 62 patients between August 1989 and June
      1992. Sixty-five percent of the patients were age over 60, and 76% (47/62) of the
      patients were Stage III or IV by pTNM. Several techniques for the IORT were
      developed and used throughout this period, including a temporary collapse of the
      right lung by unilateral tracheal incubation (for the insertion of IORT
      applicator) and an in vivo dosimetry to know the appropriate range (energy) of
      electron beam. The method of surgical treatment, the dose of external beam
      irradiation were kept standardized, and only the dose of IORT was randomized
      either to 20 or 25 Gy. IORT-related complications and the pattern of failures
      were carefully monitored. RESULTS: (a) Most prominent IORT-related complication
      was the late tracheal damage, which occurred 6 of 44 patients who were at risk
      for more than a year. (b) The incidence of IORT-induced tracheal damage was
      sharply dependent on the dose of IORT; 6 out of 21 patients who received single
      dose of 25 Gy, and none out of 33 who were given 20 Gy or less. (c) 2-year cause
      specific survival and actuarial 2-year survival were 75.0 +/- 14.5% and 62.5 +/-
      13.2%, respectively. No loco-regional recurrence has been detected at the time of
      analysis. CONCLUSION: IORT in combination with modified total esophagectomy is an
      effective and safe method to obtain a local control in advanced esophageal
      carcinomas, if the dose of IORT does not exceed 20 Gy.

PMID- 8262829
TI  - Influence of intraluminal brachytherapy dose on complications in the treatment of
      esophageal cancer.
AB  - PURPOSE: Demonstration of the influence of intraluminal brachytherapy dose on
      complications in the treatment of esophageal carcinoma. METHODS AND MATERIALS:
      Between January 1990 and June 1991, 75 patients with esophageal cancer were
      treated with external radiotherapy followed by intraluminal brachytherapy.
      Patients had a Karnofsky score of over 70, with no supra-clavicular nodal or
      distant disease. An external radiotherapy dose between 40 and 55 Gy (mean 52 Gy),
      5 times a week, 2 to 2.06 Gy/fraction, followed by a single session of
      Intraluminal brachytherapy using a locally developed, manual, afterloading
      applicator with Cs-137 sources with dose ranges of 8-10 Gy (Group 1: 42
      patients), 10-12 Gy (Group 2: 11 patients), and 12-15 Gy (Group 3: 22 patients)
      at a mean dose rate of 2.09 Gy/hr was delivered. RESULTS: The actuarial figures
      at 1 year were 39% for overall survival, 29% for disease-free survival, and 38%
      for local control. Fourteen patients (18.6%) developed complications of either an
      esophageal stricture or fistula. These were dependent on intra-luminal
      brachytherapy dose, whereas external radiotherapy and intra-luminal brachytherapy
      doses did not contribute significantly to local control. For Groups 1, 2, and 3,
      actuarial local control were 28%, 45%, and 63% (p < 0.1) and of complications
      were 6%, 20%, and 70% (p < 0.001), respectively. Also, on applying the
      Time/Dose/Fractionation formula on brachytherapy doses, it was found that the
      complication rate was 6% for TDF of < 31, 25% for TDF of 32-37, and 70% for TDF
      of > 38 (p < 0.001). CONCLUSION: External radiotherapy doses in the range of 50
      to 55 Gy followed by a dose of 10-12 Gy of intraluminal brachytherapy was found
      optimal with respect to complications and local control in the radiotherapeutic
      management of esophageal cancer.

PMID- 8262830
TI  - Management of epistaxis in Rendu-Osler disease: is brachytherapy effective?
AB  - PURPOSE: This paper reviews the results of intranasal brachytherapy for epistaxis
      in 43 patients with Rendu-Osler disease treated between 1971-1991 at Henri Mondor
      Hospital. METHODS AND MATERIALS: 2-3 intranasal catheters were afterloaded with
      192Ir sources. Computer dosimetry was performed and then the dose was prescribed
      to an isodose thought to cover the nasal mucosa. The dose rate ranged from 0.16
      Gy/h-0.63 Gy/h with a median of 0.34 Gy/h. Dose at one application ranged from 15
      35 Gy with a median of 30 Gy. The severity of epistaxis was graded 1 to 5.
      RESULTS: The time to recurrence of significant epistaxis ranged from 6-178 months
      with a median of 24 months. The dose prescribed did not correlate with control
      rate. The only brachytherapy complication was septal perforation in 4 patients;
      in one this was a result of repeated nasal coagulation. CONCLUSION: We suggest
      that intranasal brachytherapy is a useful modality in the management of epistaxis
      in Rendu-Osler disease.

PMID- 8262831
TI  - Malignant epidural spinal cord compression associated with a paravertebral mass:
      its radiotherapeutic outcome on radiosensitivity.
AB  - PURPOSE: To evaluate clinical characteristics and functional outcome of malignant
      epidural spinal cord compression associated with a paravertebral mass. METHODS
      AND MATERIALS: Between 1987 and 1990, 136 patients with epidural spinal cord
      compression were treated with irradiation. Of these, 25 patients (18%) had
      epidural spinal cord compression associated with a paravertebral mass. This
      report is based on analysis of these 25 patients. Fourteen patients received 3000
      cGy in 10 fractions. Seven received 4000 cGy in 16 fractions. Four received 2000
      cGy in 5 fractions. Motor function was evaluated by five grades. RESULTS: Lung
      cancer accounted for the majority of epidural spinal cord compression with a
      paravertebral mass (60%) followed by lymphoma (8%) and kidney tumor (8%). This
      pattern of epidural spinal cord compression has a longer duration of pain before
      developing neurologic symptoms and has a high propensity of the upper thoracic
      spine involvement by an apical lung cancers. The functional outcome of radiation
      treatment reveals a significant difference between moderately radiosensitive
      tumors (lung, prostate, cervix, esophagus) and very radiosensitive tumor
      (lymphoma). None of the nonambulatory patients became ambulatory following
      radiotherapy except for the very radiosensitive tumors. Higher doses of radiation
      treatment (4000 cGy in 16 fractions) did not improve functional outcome.
      CONCLUSION: Due to the larger tumor burden, radiation treatment for epidural
      spinal cord compression associated with a paravertebral mass is not as effective
      as treatment of epidural spinal cord compression without a paravertebral mass
      except for the very radiosensitive tumor. Therefore, combined treatment modality
      might be beneficial for improving functional outcome.

PMID- 8262832
TI  - External radiotherapy prior to thyroid cancer: a case-control study.
AB  - PURPOSE: The aim of this investigation was to study previous radiotherapy of
      malignant diseases as a risk factor for thyroid cancer. METHODS AND MATERIALS: By
      using the Swedish Cancer Registry all cases of thyroid cancer with another
      malignant disease at least one year previously and living within the catchment
      area of our hospital were traced. During 1959-1989 a total of 1056 cases of
      thyroid cancer were identified. Of these 37 had had another previous malignant
      disease and they constituted the cases in this study. As controls four persons
      with at least two malignant diseases, thyroid cancer excluded, were selected for
      each case from the same cancer registry. RESULTS: Ten (27.0%) of the 37 patients
      with thyroid cancer as a second tumor had earlier been irradiated with the
      treatment dose including the thyroid gland as compared with 34 (24.5%) of the 139
      control patients. Eight of the ten cases with previous irradiation of the thyroid
      gland had papillary cancer. The median latency was 13 years. The estimated
      radiation dose in the thyroid varied between 3 and 40 Gy. External radiotherapy
      gave a crude odds ratio of 1.1 with 95% confidence interval = 0.5-2.8 for thyroid
      cancer. The weighted odds ratio was calculated to 2.3 with confidence interval =
      0.5-8.9. CONCLUSION: This case-control study gave a non significantly increased
      odds ratio for thyroid cancer in patients with external radiotherapy including
      the thyroid gland.

PMID- 8262833
TI  - Outcome and prognostic factors in soft tissue sarcoma in the adult.
AB  - PURPOSE: To evaluate the outcome, patterns of failure and prognostic factors in
      this rare disease in adult patients treated at a single institution in the modern
      era. METHODS AND MATERIALS: The records of all patients (389 cases) with soft
      tissue sarcoma in the extremities, torso (excluding retroperitoneum), and head
      and neck managed between 1980 and 1988 were reviewed. A curative (radical)
      approach was used in 321 patients of whom 10% were recurrent lesions. The local
      management consisted of surgery alone in 54 cases, surgery and radiotherapy in
      250 and radiotherapy alone in 17. Adjuvant chemotherapy was used as a policy for
      high grade lesions in the initial five years of the study (98 cases), but was
      omitted subsequently. RESULTS: Extremity lesions fared more favourably compared
      to head and neck and torso lesions (p = 0.02) with respect to survival. Extremity
      and torso lesions had significantly better local control (p < 0.0001) than in the
      head and neck where local failure was a common cause of death. A multiple Cox
      regression analysis revealed that resection margins, local extension of tumor,
      age at diagnosis, and grade correlated with local relapse and distant relapse was
      also associated with local extension, high grade and in addition, large lesions.
      Size appeared especially predictive for distant failure, the most common cause of
      death. Distant failure was not influenced by the use of adjuvant chemotherapy.
      Patients treated for recurrence in this series had significantly worse survival
      due to increased distant failure despite similar local control to primary cases.
      CONCLUSION: This series highlights the overall problem of distant failure in this
      disease. It also reaffirms the importance of obtaining local control both in the
      head and neck, where uncontrolled local disease is the major cause of death, and
      in general since local relapse appears to increase the risk of distant failure.
      It appears that the current staging systems should be reviewed in the light of
      the apparent effect of different prognostic factors.

PMID- 8262834
TI  - Should carbogen and nicotinamide be given throughout the full course of
      fractionated radiotherapy regimens?
AB  - PURPOSE: Tumor radiosensitization with carbogen and nicotinamide (CON) was
      compared when both agents were given throughout fractionated radiotherapy with
      the sensitization observed when administered with only half of the fractions. The
      effect of overall treatment time on the local control of tumors irradiated in air
      or with CON was also investigated. METHODS AND MATERIALS: Local tumor control of
      a rodent adenocarcinoma, CaNT, was studied using eight different 20-fraction x
      ray regimens. An overall time of either 10 or 20 days was used and CON was given
      with all, the first half or last half of the treatment. RESULTS: Relative to air,
      all six sensitizer combinations gave a large and significant increase in
      sensitization (p << 0.00001). Enhancement ratios were 1.9 and 2.1 when CON was
      given with all 20 fractions in either 10 or 20 days, respectively. For both
      overall times, enhancement ratios were reduced by 15-25% when CON was given with
      only half of the fractions. In air, reducing the treatment time from 20 to 10
      days gave a small but significant decrease in the isoeffective doses. When CON
      was administered with either all or part of a schedule, varying the treatment
      time had little or no effect on local tumor control. No toxic side-effects were
      encountered when the sensitizers were administered 10 or 20 times, either once or
      twice per day. CONCLUSION: CON is an effective and non-toxic tumor
      radiosensitizer. In CaNT tumors, a significantly greater effect is seen when CON
      is given with every fraction of the schedule. The sensitizers reduced or
      abolished the sparing effect of overall time.

PMID- 8262835
TI  - Effect of irradiation on healing of newly made colonic anastomoses in the rat.
AB  - PURPOSE: Short-term effects of radiotherapy on the healing process of newly made
      colonic anastomoses are investigated by measuring the anastomotic strength in a
      rat model. METHODS AND MATERIALS: Four groups of Wistar rats were used. In all
      groups, rats underwent a 1 cm sigmoid resection with end-to-end anastomosis.
      Group I served as a control group. In group II the anastomosis was irradiated
      after closure of the abdominal wall with a single dose of 20 Gy of 250 kV x rays.
      Group III was irradiated with a single dose of 20 Gy while the abdominal wall was
      not closed, and the surrounding tissues were carefully covered by a lead plate,
      simulating intra-operative radiotherapy. Group IV was treated as group III, but a
      larger dose of 25 Gy was applied. Animals were sacrificed 3 or 7 days after the
      operation. General condition of the rats was determined by observation, weight
      loss, serum protein and albumin at sacrifice. Anastomotic healing was evaluated
      by inspection, bursting pressure, hydroxyproline and protein contents of the
      anastomotic segment. RESULTS: Direct postoperative externally irradiated rats
      (group II) showed a marked weight loss, hypoproteinaemia and hypo-albuminaemia
      because of involvement of small bowel in the irradiated volume. With respect to
      anastomotic healing there were no significant differences between control and
      irradiated groups. CONCLUSION: These data suggest that the application of a
      single dose of irradiation (20 and 25 Gy) on colonic anastomoses given in a
      direct postoperative or intraoperative model has no measurable side effect on the
      early healing of newly made colonic anastomoses. Direct postoperative external
      irradiation results in unwanted side effects in the adjacent bowel.

PMID- 8262836
TI  - In vivo radiosensitization efficacy of KU-2285 and etanidazole at clinically
      relevant low radiation doses.
AB  - PURPOSE: The in vivo radiosensitization efficacy of KU-2285 at clinically
      relevant low radiation doses (2-4 Gy) was compared with that of etanidazole using
      four types of assays with EMT6, SCCVII, and C3H mammary tumors. METHODS AND
      MATERIALS: The in vivo-in vitro cytokinesis-block micronucleus assay and the
      chromosomal aberration assay were used to assess the sensitizing effect at single
      doses of 2-4 Gy. After in vivo treatment for tumors, tumor cells were cultured in
      the presence of cytochalasin B for the former assay or demecolcine for the latter
      assay, and the micronucleus frequency in binucleate cells and the chromosomal
      frequency in metaphase cells were evaluated after 42 hr and 3 hr of culture. In
      addition, an in vivo-in vitro colony assay and a growth delay assay were
      performed using fractionated irradiation regimens (4 Gy x 5). RESULTS: The
      sensitizer enhancement ratio for 100-400 mg/kg of KU-2285 was between 1.12 and
      1.42. KU-2285 was a more efficient sensitizer than etanidazole in 3 of 9
      experiments and as efficient as etanidazole in the remaining six experiments.
      CONCLUSION: Both the micronucleus assay and the chromosomal aberration assay
      appeared to be very useful in evaluating the in vivo sensitizing effect at low
      radiation doses. KU-2285 had a definite radiosensitizing effect even at low
      radiation doses, and clinical trials of KU-2285 may be warranted.

PMID- 8262837
TI  - Derivations of relative biological effectiveness for the high-let radiations
      produced during boron neutron capture irradiations of the 9L rat gliosarcoma in
      vitro and in vivo.
AB  - PURPOSE: Relative biological effectiveness (RBE) values for the high linear
      energy-transfer particles produced during boron neutron capture therapy have
      generally been based on theoretical considerations or in vitro experiments. The
      purpose of this study was to independently determine RBE values for all of the
      boron neutron capture therapy dose components. METHODS AND MATERIALS: Clonogenic
      cell survival data were obtained for 9L rat gliosarcoma cells irradiated in the
      Brookhaven Medical Research Reactor thermal neutron beam both in vitro and as an
      intracerebral tumor. These data were analyzed using the linear quadratic model
      for cell survival to derive measured RBE values for all beam components and for a
      number of different boron compounds. RESULTS: In the absence of boron, the
      combined effects of the protons from the nitrogen capture, 14N(n,p)14C, and the
      fast neutron scatter, 1H(n,n')p, reactions generated RBEs of 3.7 in vitro and 3.2
      in an in vivo/in vitro excision assay, compared to 250 kVp X rays using an end
      point of 1% cell survival. Apparent RBEs for the 10B(n,alpha)7Li reaction
      products were calculated from cell survival data following reactor irradiations
      in the presence of the amino acid p-boronophenylalanine, the sulfhydryl
      dodecaborate monomer or dimer, or boric acid. Apparent RBEs for the
      10B(n,alpha)7Li reaction ranged from 1.2 to 9.8 depending on which boron compound
      was used. RBEs from the in vitro studies were consistently higher than from the
      in vivo/in vitro studies. Under any conditions, the apparent RBE for the
      10B(n,alpha)7Li reaction with p-boronophenylalanine was higher than that with any
      other boron compound tested. CONCLUSIONS: Generally accepted RBE values for the
      fast neutron and 14N(n,p)14C reaction components of the total dose are too low.
      The apparent RBEs calculated for the 10B(n,alpha)7Li reaction were compound
      dependent and consistent with differences in the distribution of 10B relative to
      glioma cell nuclei.

PMID- 8262838
TI  - Calculating potential doubling time using monoclonal antibodies specific for two
      halogenated thymidine analogues.
AB  - PURPOSE: A new flow cytometric technique that allows for two-incorporated
      thymidine analogues to be measured simultaneously and independently has been used
      to improve the accuracy of in vivo cell kinetic estimates, i.e., the length of S
      phase (TS) and potential doubling time (Tpot). METHODS AND MATERIALS: The
      analogues chlorodeoxyuridine and iododeoxyuridine were injected at different
      times into mice bearing the mouse mammary tumor MCaK. At different times after
      labeling, the tumors were harvested and prepared for three color flow cytometric
      analysis of DNA, chlorodeoxyuridine, and iododeoxyuridine. Control experiments
      showed that similar estimates of Tpot were obtained from each label when
      administered singly, or as staggered pulses. Comparisons were made between TS and
      Tpot calculated from a single label (single point), from the averaged result of
      the two labels from the same tumor (two point-ave), and from the simultaneous
      nonlinear fitting of the measured parameters from the two labels, from the same
      tumor (two point-fit). These estimates of TS and Tpot were then compared to
      reference values obtained by fitting the pooled measured parameters from all the
      tumors, that were labeled for different periods of time. RESULTS: While all of
      the methods resulted in similar mean estimates of TS and Tpot that were close to
      the reference values, the fewest assumptions, and the least variability in the
      results, were obtained using the two point-fit data. CONCLUSION: The estimation
      of Tpot using two thymidine analogues is more accurate than that obtained from a
      single label.

PMID- 8262839
TI  - Tissue tolerance of normal and surgically manipulated canine liver to
      intraoperative radiation therapy (IORT).
AB  - PURPOSE: The purpose of the study is to obtain dose guidelines for the delivery
      of intraoperative radiotherapy to the liver of patients with colorectal liver
      metastases. Following partial resection of the liver, a single high dose of 10,
      20, 25, and 30 Gy intraoperative radiotherapy was applied to both the resection
      plane as well as a nonsurgically manipulated part of the liver of 25 beagles. The
      temporal sequence of histological and ultrastructural changes of these irradiated
      parts of the liver tissue was investigated. METHODS AND MATERIALS: The
      feasibility of delivering single large dose of intraoperative electron beam
      radiotherapy to the normal and partially hepatectomized liver was experimentally
      investigated in a canine study. RESULTS: There were no postoperative
      complications, no morbidity or mortality with a minimal follow-up of 1 year.
      Autopsy performed 3 months following irradiation showed only mild
      histopathological changes. One year following intraoperative radiotherapy more
      distinct histopathological changes consisting of capsular thickening, diffuse
      parenchymal fibrosis and subcapsular hepatocellular atrophy were found. The liver
      function remained intact. CONCLUSION: This study demonstrated that intraoperative
      radiotherapy to part of the liver in the canine model can be safely applied and
      doses up to 30 Gy are well tolerated.

PMID- 8262840
TI  - Erythropoietin increases hemoglobin in cancer patients during radiation therapy.
AB  - PURPOSE: The hemoglobin (Hgb) level of patients during radiation therapy is
      associated with both survival and local tumor control in several organ sites.
      This clinical trial tested whether administering recombinant human erythropoietin
      (r-HuEPO) to cancer patients would increase their Hgb level during the course of
      radiation therapy without adverse effects. METHODS AND MATERIALS: The 40
      participating patients had a Hgb value < 13.5 g/dL and a malignant tumor located
      above the diaphragm without evidence of distant metastasis for which they were
      scheduled to undergo a 5-8 week course of daily radiation therapy. All 40
      patients were given oral ferrous sulfate throughout their radiation therapy
      course. Half the patients also received 150-300 mg/kg of r-HuEPO subcutaneously
      three times per week starting 0-10 days prior to the first dose of radiation.
      RESULTS: The r-HuEPO and control groups did not differ significantly in patient
      age, gender, tumor type, initial hemoglobin, erythropoietin, or iron
      bioavailability. The Hgb level increased more than 6% during radiation therapy in
      all 20 of the r-HuEPO patients but in only 2/20 of the control patients (p <
      0.001). The Hgb rose from a mean +/- standard deviation of 11.9 +/- 1.3 g/dL to >
      14 g/dL during radiation therapy in 80% of the r-HuEPO group compared to in 5% of
      the control group (p < 0.001). The mean +/- s.d. change in Hgb concentration
      during radiation therapy was 27 +/- 15% (an average rise of 5% per week) in the r
      HuEPO group and 0 +/- 6% in the control group (p < 0.001). r-HuEPO had no
      significant measurable effect on blood pressure, white blood cell, neutrophil or
      platelet count, or liver or renal function. The only reported adverse effect of r
      HuEPO administration was an asymptomatic skin rash in one patient. CONCLUSION: r
      HuEPO with ferrous sulfate significantly increased the Hgb level in cancer
      patients without interfering with their course of radiation therapy, whereas
      ferrous sulfate alone did not. r-HuEPO appears to be a safe and effective means
      of increasing red cell mass during radiation therapy.

PMID- 8262841
TI  - High-dose preoperative external beam and intraoperative irradiation for locally
      advanced pancreatic cancer.
AB  - PURPOSE: To analyze results of high-dose preoperative external beam irradiation
      followed by surgical exploration and intraoperative radiation therapy in patients
      with unresectable pancreatic cancer. METHODS AND MATERIALS: From December 1983
      through December 1990, 27 patients with primary unresectable but localized
      pancreatic adenocarcinoma received high-dose (50 to 54 Gy) external beam
      irradiation with or without concomitant bolus 5-fluorouracil followed by surgical
      exploration and intraoperative electron beam irradiation (20 Gy) at the Mayo
      Clinic. RESULTS: Local control was achieved in 21 of 27 (78%) patients. Actuarial
      local control at 1, 2, and 5 years was 86%, 68%, and 45%, respectively. In 19
      (70%) of the 27 patients, distant metastasis developed, and peritoneal or liver
      progression (or both) was found in 14 (52%). The actuarial distant metastasis
      rate at 2 and 5 years was 69% and 83%, respectively. Median survival from the
      date of diagnosis was 14.9 months. Actuarial 2- and 5-year overall survival was
      27% and 7%, respectively. These survival rates are higher (p = 0.001) than the 6%
      and 0% actuarial 2- and 5-year survival observed in 56 patients who underwent
      intraoperative radiation therapy followed by postoperative high-dose external
      beam treatment at our institution. CONCLUSION: Administering the full component
      of external beam irradiation before exploration and intraoperative radiation
      therapy may be more appropriate because it allows better patient selection.
      Unfortunately, altered patient selection was not effective in decreasing the
      relative risk of abdominal failure. Because effective systemic chemotherapy does
      not currently exist, whole abdominal irradiation alone or in combination with
      chemotherapy warrants evaluation.

PMID- 8262842
TI  - Reirradiation for rectal cancer and surgical resection after ultra high doses.
AB  - PURPOSE: Local recurrence of rectal cancer following high-dose pelvic radiation
      presents a difficult management challenge. Conventional wisdom suggests that
      reirradiation should be avoided and radical pelvic surgery is hazardous after
      ultra high-dose radiation. METHODS AND MATERIALS: In a unique Phase I/II pilot
      study, 32 patients with recurrent rectal cancers following previous pelvic
      radiation underwent planned reirradiation to the pelvis. Initial radiation doses
      had ranged from 30-64.87 Gy (median dose 45 Gy). Seventeen patients underwent
      reirradiation followed by radical resection. Fifteen patients were reirradiated
      for palliative relief of symptoms. Treatment techniques consisted of two lateral
      fields (7 x 7 to 12 x 10 cm) encompassing the tumor with 2 cm margins.
      Reirradiation doses ranged from 19.80-47.66 Gy, (median 34.2 Gy). Patients also
      received concurrent low-dose continuous infusion chemotherapy, (5-FU 200-300
      mg/day). Total cumulative radiation doses ranged from 70.6 to 111.6 Gy. RESULTS:
      Treatment was well tolerated. Four patients had radiation
      interrupted/discontinued for diarrhea or leukopenia. Follow-up ranges from 6
      months to 36 months. No late sequelae of radiation have been observed to date.
      Seventeen patients underwent surgical exploration 6-8 weeks following
      reirradiation. Two patients had extensive disease and were not resected. Fifteen
      patients underwent radical resection of residual tumor (4 posterior
      exenterations, 6 APR, 3 transanal abdominal transanal proctocolectomy with
      coloanal anastomosis (TAATA), and 2 LAR). No patients died postoperatively. No
      excessive edema, hemorrhage, or adhesions were observed. Two patients developed
      pelvic abscess and one developed a coloanal stricture. Eleven of 15 resected
      patients are alive from 6 to 36 months with a 2-year survival of 66%. Of the
      patients treated palliatively, symptomatic relief was observed in 13/15 patients.
      No objective complete response was observed, but 6/15 patients had measurable
      partial response. Median survival in this group was 14 months. CONCLUSION: Based
      on this experience, we believe that in selected patients radical surgical
      resection after cumulative ultra high doses (70-90 Gy) of radiation can be
      performed safely. A viable anastomosis is also possible in spite of these high
      doses. Planned reirradiation for palliative relief of symptoms can be effective
      without unusual risks of complication. Long-term effects of such ultra high dose
      radiation and surgery continue to be monitored.

PMID- 8262843
TI  - Potential doubling time in head and neck tumors treated by primary radiotherapy:
      preliminary evidence for a prognostic significance in local control.
AB  - PURPOSE: The aim of the study was to determine preliminarily whether cell kinetic
      parameters evaluated using in vivo infusion of bromodeoxyuridine (BrdUrd) and
      flow cytometry, play a role as prognostic factors of loco-regional control in
      squamous cell head and neck carcinoma treated with radiotherapy. METHODS AND
      MATERIALS: Between April 1989 and December 1991, 42 patients with unresectable
      Stage II-IV squamous cell carcinoma of the oral cavity, pharynx or larynx were
      given an infusion of BrdUrd solution prior to primary tumor biopsy sampling at 4
      6 hr later. The simultaneous labeling S-phase fraction (LI) and duration (Ts) as
      well as the estimated potential doubling time (Tpot) were measured using flow
      cytometric analysis of BrdUrd and DNA content. Twenty-six patients received
      standard radiotherapy (70 Gy/35 fractions/7 weeks) whereas 15 patients were
      treated with the concomitant boost technique (75 Gy/40 fractions/6 weeks).
      RESULTS: A complete set of flow cytometric data was available for 31 patients.
      The median value of LI, Ts, and Tpot were 9%, 9 hr and 5 days, respectively.
      Univariate analysis among the patients treated homogeneously by standard
      radiotherapy, indicated that local control was affected by Tpot value (p = 0.02).
      When the same analysis was performed for the patients treated with either
      standard radiotherapy or concomitant boost regimen, we found a p = 0.04. Thus,
      patients with a tumor Tpot value < or = 5 days had a significantly lower three
      year local control than patients with Tpot > 5 days. Log-rank test univariate
      analysis showed, in addition, that nodal status was the strongest prognostic
      factor of local control (p = 0.005). Age, tumor stage, tumor site, performance
      status, grading, radiotherapy regimen, DNA ploidy and LI value were, instead, not
      significantly related to loco-regional control. Finally, when comparing the type
      of radiotherapy for tumors with Tpot < or = 5 days, we found a trend toward a
      better local control after concomitant boost regimen, with respect to standard
      regimen (p = 0.06). CONCLUSION: The present preliminary results suggest that Tpot
      could play a role as additional prognostic factor influencing the disease outcome
      in head and neck carcinoma treated by radiotherapy.

PMID- 8262845
TI  - Radiation therapy in endemic (African) Kaposi's sarcoma.
AB  - PURPOSE: Evaluating the role of radiation therapy in the treatment of the
      endemic, African variant of Kaposi's sarcoma. A retrospective analysis. METHODS
      AND MATERIALS: Between 1978 and 1990, 28 symptomatic African patients with the
      African Human Immunodeficiency Virus negative type of Kaposi's sarcoma were
      referred to the Johannesburg General Hospital. Following staging, all patients
      were treated with radiation therapy. Doses ranged between 8-10 Gy (single
      fraction) or 14-24 Gy fractionated over 1-3 weeks. RESULTS: Complete and partial
      regression of cutaneous lesions was achieved in 9 (32%) and 15 (54%) patients,
      retrospectively. A complete/near-complete alleviation of symptoms was achieved in
      all patients. Response rate and duration of response was not influenced by age,
      radiation modality or schedule. Side effects were minimal. CONCLUSION: Our study
      emphasizes the high radiosensitivity of the endemic, African type of Kaposi's
      sarcoma, indicating its usefulness as the treatment of choice for this disease.

PMID- 8262844
TI  - Prospective comparison of in vitro normal cell radiosensitivity and normal tissue
      reactions in radiotherapy patients.
AB  - PURPOSE: This pilot study was undertaken to assess the relationship between in
      vitro radiosensitivity of different normal cell types and the type and severity
      of normal tissue reactions in individual patients after radiotherapy. METHODS AND
      MATERIALS: Twenty-one patients with head and neck cancer were studied
      prospectively; four with head and neck and two with breast cancer were studied
      retrospectively. The retrospective cases were chosen because they exhibited
      unusual (severe or minimal) normal tissue reactions after radiotherapy. Small
      skin biopsies and blood samples were obtained and used to generate in vitro
      fibroblast and lymphocyte cultures, respectively. Clonogenic assays were used to
      measure in vitro fibroblast and lymphocyte radiosensitivity after high- and low
      dose rate irradiation. Head and neck patients were treated by conventional,
      hyperfractionated, or concomitant boost regimens, which have been found to yield
      an equal probability of late normal tissue reactions. The highest dose received
      by each normal tissue in the target volume was estimated using computed
      tomography treatment plans. The median patient follow-up time was 19 months
      (range: 13-25). RESULTS: The distributions of in vitro radiosensitivity
      parameters and the grade of tissue reaction scores in the patients showed a broad
      range between individuals. When in vitro parameters were compared to the acute
      and late tissue reactions, the radiosensitivity of fibroblasts, measured as
      surviving fraction at 2 Gy after high-dose rate irradiation, showed a highly
      significant correlation with the maximum grade of late effects (p < 0.0001 for
      the whole group and p = 0.0013 for the group of patients studied prospectively).
      No significant correlation was found between fibroblast radiosensitivity and
      maximum grade of acute effects or between lymphocyte radiosensitivity and either
      acute or late effects. CONCLUSION: We conclude that individuals vary in normal
      cell radiosensitivity, and that in vitro measurements of fibroblast
      radiosensitivity may predict the magnitude of late normal tissue reactions after
      radiotherapy. These preliminary results, however, need to be validated in a
      larger group of patients.

PMID- 8262846
TI  - A multivariate analysis of prognostic factors in management of pineal tumor.
AB  - PURPOSE: A multivariate analysis of prognostic factors of treatment outcome of
      pineal tumor. METHODS AND MATERIALS: From February 1979 to June 1987, 25 patients
      with primary pineal tumors were treated in our department. Patients were treated
      with either AECL Co-60 unit or 10 MV linear accelerator to the primary tumor with
      an adequate margin or to the whole brain (median dose of 36 Gy) with or without a
      cone-down boost of 10 to 20 Gy. Craniospinal irradiation was performed in two
      patients with positive CSF cytology. Minimum follow-up was 40 months. Patients
      were further stratified according to tumor type. Group I consisted of seven
      patients with pineal germinoma. Group II included nine patients with
      nongerminoma, and Group III represented nine patients treated without a
      histological verification but clinical diagnosis. RESULTS: The relapse-free
      survival (RFS) of Group I patients was 100% and 86% at 2 and 5 years,
      respectively. Relapse-free survival was 55% and 21% at 2 and 5 years,
      respectively, for Group II patients. Six of 9 patients in Group II died of
      disease due to either local recurrence or tumor seeding. Eight of 9 patients in
      Group III remain no evidence of disease, and RFS was 89% at 2 and 5 years.
      Multivariate analysis revealed that tumor histology is the only significant
      prognosticator. Age, gender, type of surgical procedure, RT field, and tumor dose
      were not. Cox's regression model also failed to demonstrate a significant
      correlation of tumor seeding with the type of surgery. CONCLUSION: The type of
      tumors in the pineal region dictates the treatment outcome. Definitive radiation
      therapy is effective in controlling germinoma, whereas a more aggressive approach
      is needed to improve local control for nongerminoma. For a localized pineal
      lesion, we advocate that treatment can be tailored to the primary tumor with
      adequate margins. However, for locally advanced tumors whole brain or
      craniospinal irradiation should be considered. No definitive correlation between
      type of surgery and the probability of tumor seeding was identified.

PMID- 8262847
TI  - Use of ultrasound to guide radiation boost planning following lumpectomy for
      carcinoma of the breast.
AB  - PURPOSE: To determine if sonographic localization of the breast lumpectomy site
      is feasible and useful in boost planning. METHODS AND MATERIALS: The operative
      beds following lumpectomy were localized by ultrasound in 22 patients (15
      infiltrating ductal, 7-ductal carcinoma in situ; size: .4-2.0 cm). Twelve
      patients had two ultrasound examinations on different days for a total of 34
      examinations. Twenty-one patients had their course of boost electron therapy
      planned using ultrasound to guide field placement. While the patient was in the
      treatment position, the surgical scar was placed at the machine's isocenter. With
      the electron cone in place, the ultrasound transducer was placed within the cone
      on top of the surgical scar. The biopsy site was localized and the light field
      maneuvered so that it's central axis would follow the axis of the transducer,
      transecting both the scar and biopsy site. RESULTS: The operative bed was highly
      visible in 26 ultrasound examinations, visible in 7, and subtly visible in 1.
      Every biopsy site showed some hypoechoic area but most appeared as the mixed
      hypoechoic pattern. Ultrasound appearances were mixed or mostly hypoechoic (28),
      anechoic with irregular walls (4), and echoic (hypoechoic compared to parenchyma)
      (2). In two cases the surgeon placed surgical clips in the operative bed, and in
      both cases several of these clips could be identified at the margins of the
      operative bed as hyperechoic foci with shadowing. The mean depth of the operative
      bed was 21 mm (range 17-36 mm). In 12 patients, two ultrasound examinations were
      performed on different days, and the mean depth difference between these scans
      was 2 mm with a range of 0-5 mm. Among patients with two scans we found that both
      the location and appearance of the operative bed was highly reproducible.
      CONCLUSION: Ultrasound can successfully be used to localize the biopsy site and
      facilitate boost field placement in patients treated with lumpectomy and
      radiation.

PMID- 8262848
TI  - An evaluation of two methods of anatomical alignment of radiotherapy portal
      images.
AB  - PURPOSE: Two techniques have been developed at our institution to allow
      anatomical registration of digitized portal images to a simulation film. Accuracy
      of the portal image alignment methods is tested and single intrauser and multiple
      interuser variation is examined using each technique. METHODS AND MATERIALS:
      Method one requires the identification of anatomical fiducial points on a
      simulation image and its corresponding portal image. The parameters required to
      align the corresponding points are calculated by a least squares fit algorithm.
      Method two uses an anatomical template generated from the simulation image and
      superimposing it upon a portal image. The template is then adjusted by a computer
      mouse to obtain the best subjective anatomical fit on the portal image.
      Megavoltage portal images of a skull phantom with various known shifts and eight
      clinical image files were aligned by each method. Each data set was aligned
      several times by both a single user and multiple users. RESULTS: Alignment of the
      anatomical phantom portal images demonstrates an accuracy of less than 0.8 +/-
      0.9 mm and 0.7 +/- 1.0 degrees with either method. As out of plane rotation
      increased from 0 to 5 degrees, simulating out of plane malpositioning, alignment
      orthogonal to the plane of rotation worsened to 1.5 +/- 1.1 mm with the point
      method and 2.4 +/- 1.6 mm with the template method. Alignment parallel to the
      axis of the gantry rotation was insensitive to this change and remained constant
      as did the rotational alignment parameters. For the clinical image files the
      magnitude of variation for a single user is typically less than +/- 1 mm or +/- 1
      degree. The magnitude of variation of alignment increased when multiple users
      aligned the same image files. The variation was dependent upon anatomical site
      and to a lesser degree the method of alignment used. The root mean square
      deviation of translational shifts range from +/- 0.68 mm when using the template
      method in the pelvis to as high as +/- 2.94 mm with the template method to align
      abdominal portal images. In the thorax and pelvis translational alignments along
      the horizontal axis were more precise than along the vertical axis. Multiple user
      variability was in part due to poor image quality, user experience, non rigidity
      of the anatomical features, and the difficulty in locating an exact point on a
      continuous anatomical structure. CONCLUSION: In well controlled phantom studies
      both the fiducial point and template method provide similar and adequate results.
      The phantom studies show that alignment error and variance increase with
      distortion in anatomical features secondary to out of plane rotations. In
      clinical situations intrauser variation is small, however, multiple interuser
      variation is larger. The magnitude of variation is dependent upon the anatomical
      site aligned.

PMID- 8262849
TI  - A technique using parallel-opposed high energy electron beams for reirradiation
      of tumors near the spinal cord.
AB  - PURPOSE: Previous radiation treatment of patients with recurrent Hodgkin's
      lymphoma hampers attempts to give these patients further radiation treatment for
      their recurrence, because of the potential for serious radiation damage to
      critical normal structures within the treatment volume. The purpose of this paper
      is to present a technique we developed for treatment of recurrent Hodgkin's
      lymphoma in mediastinum and hilum. The technique is based on parallel-opposed
      electron beams with a spinal cord shield in the posterior electron beam. METHODS
      AND MATERIALS: The patient was treated with parallel-opposed 20 MeV electron
      beams and the spinal cord shield was shaped in such a way that the total dose
      from both the anterior and posterior electron beams did not exceed 33% of the
      prescribed tumor dose. Wax bolus was used to obtain the desired separation for
      the electron beams. RESULTS: In an electron beam, the dose under the spinal cord
      shield depends not only on the depth of the spinal cord but also on the width of
      the shield. For a given shield width, as the cord depth increases the relative
      dose under the shield first increases, reaches a maximum, and then decreases to
      approach the open field depth dose data at large depths. The depth at which the
      relative dose maximum occurs increases slowly with the shielded width. At a given
      depth, the relative dose decreases with an increasing shield width. CONCLUSION:
      Parallel-opposed electron beams with a spinal cord shield in the posterior
      electron beam provide a viable option in treatment of tumors enveloping the
      spinal cord. A high tumor dose may be prescribed with a concurrent low dose to
      the spinal cord obtained with an appropriately shaped spinal cord shield.

PMID- 8262850
TI  - Concurrent treatment planning for outpatient high dose rate prostate template
      implants.
AB  - PURPOSE: Since November of 1991, we have treated locally advanced (B2-C) prostate
      cancer using external beam radiotherapy integrated with outpatient high dose rate
      interstitial implant boost as part of a Phase II clinical trial. This required
      (a) rapid, automated planning; (b) incorporation of image data and (c) dose
      optimization. METHODS AND MATERIALS: A treatment planning system was designed
      which integrates imaging and needle guidance with source reconstruction and dose
      display. All components of treatment planning (reconstruction, optimization, dose
      prescription, dose display) are largely automated. A rectal reference point was
      defined which was reproducible and easily verified. No pretreatment planning was
      required. RESULTS: As of November 1992, 83 treatments were delivered using this
      system. Intra-operative treatment decisions were made possible due to the speed
      and ease of interpretation of the system. The system has proven satisfactory in
      the operating room. Rectal doses were calculated for all patients, and ranged
      from 35-79% of the prescribed dose, with a mean of 58%. The first echelon of a
      Phase II escalating dose trial has been completed, with 22 patients treated over
      a period of 1 year. CONCLUSION: Outpatient high dose rate brachytherapy appears
      to be a practical means of boosting locally advanced prostate cancer patients.
      Rapid treatment planning is possible incorporating on-line ultrasound images to
      allow immediate dose optimization to be performed during and after implant
      placement.

PMID- 8262851
TI  - A technique for fractionated stereotactic radiotherapy in the treatment of
      intracranial tumors.
AB  - PURPOSE: The excellent treatment results obtained with traditional radiosurgery
      have stimulated attempts to broaden the range of intracranial disorders treated
      with radiosurgical techniques. For major users of radiosurgery this resulted in a
      gradual shift from treating vascular diseases in a single session to treating
      small, well delineated primary tumors on a fractionated basis. In this paper we
      present the technique currently used in Montreal for the fractionated
      stereotactic radiotherapy of selected intracranial lesions. METHODS AND
      MATERIALS: The regimen of six fractions given every other day has been in use for
      "fractionated stereotactic radiotherapy" in our center for the past 5 years. Our
      current irradiation technique, however, evolved from our initial method of using
      the stereotactic frame for target localization and first treatment, and a "halo
      ring" with tattoo skin marks for the subsequent treatments. Recently, we
      developed a more precise irradiation technique, based on an in-house-built
      stereotactic frame which is left attached to the patient's skull for the duration
      of the fractionated regimen. Patients are treated with the stereotactic dynamic
      rotation technique on a 10 MV linear accelerator (linac). RESULTS: In preparation
      for the first treatment, the stereotactic frame is attached to the patient's
      skull and the coordinates of the target center are determined. The dose
      distribution is then calculated, the target coordinates are marked onto a Lucite
      target localization box, and the patient is placed into the treatment position on
      the linac with the help of laser positioning devices. The Lucite target
      localization box is then removed, the target information is tattooed on the
      patient's skin, and the patient is given the first treatment. The tattoo marks in
      conjunction with the target information on the Lucite target localization box are
      used for patient set-up on the linac for the subsequent 5 treatments. The
      location of the target center is marked with radio-opaque markers on the target
      localization box and verified with a computerized tomography scanner prior to the
      second treatment. The same verification is done prior to other treatments when
      the target center indicated by the target localization box disagrees with that
      indicated by the tattoo marks. The new position of the target center is then
      determined and used for treatment positioning. CONCLUSION: The in-house-built
      frame is inexpensive and easily left attached to the patient's skull for the 12
      day duration of the fractionated regimen. Positioning with the Lucite target
      localization box verified with tattoo marks ensures a high level of precision for
      individual fractionated treatments.

PMID- 8262852
TI  - Radiation Therapy Oncology Group: radiosurgery quality assurance guidelines.
AB  - A multidisciplinary Radiation Therapy Oncology Group (RTOG) task force has
      developed quality assurance guidelines for radiosurgery. The purpose of the
      guidelines are fourfold: (1) To ensure that participating institutions have the
      proper equipment and appropriate technique(s) to administer radiosurgery; (2) to
      outline a standard data set for each treated patient to assess protocol
      compliance; (3) to define minor and major deviations in protocol treatment; and
      (4) to set forth clinical data necessary to determine treatment efficacy,
      including failure patterns, and treatment toxicity. These guidelines are being
      implemented into active and developing radiosurgery protocols.

PMID- 8262853
TI  - Consensus guidelines for high dose rate remote brachytherapy in cervical,
      endometrial, and endobronchial tumors. Clinical Research Committee, American
      Endocurietherapy Society.
AB  - PURPOSE: A large number of medical centers have recently instituted the use of
      High Dose-Rate Afterloading Brachytherapy (HDRAB). There is wide variation in
      treatment regimens, techniques, and dosimetry being used and there are no
      national standard protocols or guidelines for optimal therapy. METHODS AND
      MATERIALS: The Clinical Research Committee (CRC) of the American Endocurietherapy
      Society (AES) met to formulate consensus guidelines for HDRAB in cervical,
      endometrial, and endobronchial tumors. CONCLUSION: Each center is encouraged to
      follow a consistent treatment policy in a controlled fashion with complete
      documentation of treatment parameters and outcome including efficacy and
      morbidity. Until further clinical data becomes available, the linear quadratic
      model can be used as a guideline to formulate a new HDR regimen exercising
      caution when changing from a Low Dose Rate (LDR) to a HDRAB regimen. The
      treatments should be fractionated as much as practical to minimize long term
      morbidity. As more clinical data becomes available, the guidelines will mature
      and be updated by the Clinical Research Committee of the AES.

PMID- 8262854
TI  - Intraperitoneal cisplatin and regional hyperthermia for ovarian carcinoma.
AB  - PURPOSE: To review the theoretical basis and results of a Phase I study of
      concurrent intraperitoneal cisplatin and hyperthermia in the treatment of ovarian
      carcinoma. METHODS AND MATERIALS: Previously treated patients with epithelial
      ovarian carcinoma received intraperitoneal instillation of cisplatin and 60
      minutes of regional hyperthermia, with a goal temperature of 41.5 degrees C.
      Cisplatin dose started at 20 mg/m2 with escalation to the maximally tolerated
      dose. Six such cycles given every 3 weeks were planned. Pharmacokinetic studies
      with and without hyperthermia were performed. RESULTS: Fifteen patients receiving
      17 courses of treatment were evaluable. The maximally tolerated dose of cisplatin
      was between 80 and 120 mg/m2. The dose limiting toxicity was nephrotoxicity in
      all but one course. The median intraperitoneal temperature was 40.7 degrees C;
      the majority of treatments in which the goal temperature was not reached had
      power limited by patient discomfort. No major toxicities attributable to
      hyperthermia were noted. Pharmacokinetic studies noted no significant differences
      between treatments with vs. without hyperthermia, with intraperitoneal to plasma
      area under the curve ratios being 30-35. Ten patients had a decline in their CA
      125 count during treatment, although in only two patients did this response
      persist beyond their course of treatment. CONCLUSION: Intraperitoneal cisplatin
      and regional hyperthermia can be performed with reasonable toxicity. The
      maximally tolerated dose of 80-120 mg/m2 in pretreated patients (which is similar
      to those reported with cisplatin alone) and median intraperitoneal temperatures
      of 40.7 degrees C, however, are felt to be too low to be efficacious in a
      significant percentage of women with bulky recurrent disease. Further study using
      intravenous thiosulfate and controlled analgesia is being performed.

PMID- 8262855
TI  - Pituitary adenomas: evolving diagnosis and management.

PMID- 8262856
TI  - Radiation to the intact groin.

PMID- 8262857
TI  - The magainins: antimicrobial peptides with potential for topical application.

PMID- 8262858
TI  - Antibacterial activities of non-antibiotic drugs.
AB  - Antibacterial activities of several 'non-antibiotic drugs' used in treatment of a
      variety of non-infectious human diseases have been observed. Such an effect has
      been noticed for barbiturates, beta-adrenergic receptor antagonists, diuretic
      drugs, H1 antihistamines, mucolytic agents, nonsteroid anti-inflammatory drugs,
      proton pump inhibitors and psychotherapeutic drugs. A synergic or antagonistic
      effect with antibiotics of several of these drugs have also been noticed. In this
      overview the knowledge in the field is summarized, omitting hormones, drugs with
      local effects and those with low therapeutic indexes. Therapeutic implications
      and future considerations are discussed.

PMID- 8262859
TI  - High-level fluoroquinolone resistance in a Salmonella typhimurium isolate due to
      alterations in both gyrA and gyrB genes.
AB  - A clinical isolate of Salmonella typhimurium serovar copenhagen (80190) with high
      level fluoroquinolone resistance (MIC ciprofloxacin 32 mg/L) was examined for the
      occurrence of alterations of gyrA and gyrB by a dominance test with the
      introduction of plasmids carrying either the gyrA or the gyrB gene of Escherichia
      coli K-12. Either plasmid resulted in enhanced susceptibilities of each of the
      resulting heterodiploid strains. Introduction of a plasmid carrying both gyrA and
      gyrB genes into S. typhimurium 80190 restored the wildtype sensitivity. These
      observations provide evidence that alterations of both gyrA and gyrB are
      responsible for the high-level fluoroquinolone resistance of this isolate of S.
      typhimurium.

PMID- 8262861
TI  - Metronidazole uptake by sensitive and resistant isolates of Helicobacter pylori.
AB  - The development of metronidazole resistance in Helicobacter pylori has become an
      important factor in the clinical use of this drug in the treatment of gastritis
      and peptic ulcers. The mechanism for the development of resistance is not known
      but may involve factors which influence metronidazole uptake and metabolism. In
      this study, a simple and reliable HPLC assay for metronidazole was developed and
      the uptake of the drug from broth cultures of both resistant and sensitive
      strains of H. pylori was investigated. Resistance to metronidazole was determined
      by the E test as well as plate and broth assays. In the presence of the
      antibiotic (approximately 10 mg/L), metronidazole-sensitive strains were killed
      within 24 h and there was a concomitant fall in the concentration of
      metronidazole in the broth. In contrast, the killing of resistant strains of H.
      pylori was associated with < 10% loss of antibiotic from broth. These differences
      in metronidazole uptake are ascribed to alterations in the mechanisms of action
      of the drug in sensitive and resistant strains.

PMID- 8262860
TI  - Mechanisms of quinolone resistance in clinical isolates: accumulation of
      sparfloxacin and of fluoroquinolones of various hydrophobicity, and analysis of
      membrane composition.
AB  - The accumulation of sparfloxacin and three other fluoroquinolones of decreasing
      hydrophobicity, pefloxacin, ofloxacin, and ciprofloxacin, into randomly chosen
      fluoroquinolone-sensitive and -resistant clinical isolates of bacteria (four
      Enterobacteriaceae, one Pseudomonas aeruginosa and one Staphylococcus aureus) was
      measured. There was good correlation between the concentration of drug that
      inhibited early DNA synthesis in whole cells and the MIC values of the same drug
      regardless of organism sensitivity or the quinolone. A decrease in permeability
      in resistant strains compared with sensitive, due to a modification of outer
      membrane proteins was often involved in resistance. But, in all cases other
      mutations may also be involved explaining the relatively high level of resistance
      of the strains. In two resistant strains the DNA gyrase was purified and found to
      be resistant to inhibition by quinolones. The use of quinolones of differing
      hydrophobicity emphasized the importance of this property in the uptake of
      quinolones by bacterial cells, and provided evidence that sparfloxacin used both
      porin and the self-promoted uptake pathway for it's uptake.

PMID- 8262862
TI  - Antimicrobial susceptibility testing of enterococci: results of a survey
      conducted by the United Kingdom National External Quality Assessment Scheme for
      Microbiology.
AB  - Six strains of enterococci were distributed to participants in the United Kingdom
      National External Quality Assessment Scheme for Microbiology with a request that
      they be tested for susceptibility to ampicillin/penicillin and vancomycin and for
      high-level resistance to gentamicin. More than 98% of laboratories correctly
      reported the resistant strains as resistant to penicillin and ampicillin.
      However, there was a poorer correlation for the susceptible strains, with only 1
      6% and 69-83% of laboratories reporting the strains as susceptible to penicillin
      and ampicillin respectively. Those laboratories which used 5-25 micrograms
      ampicillin discs or breakpoint methods reported proportionally more results
      correctly for the susceptible strains than those using 2 micrograms discs.
      Participants using Escherichia coli or an enterococcus as a control and those not
      using a control at all were more likely to report ampicillin-susceptible strains
      correctly than those using Staphylococcus aureus NCTC 6571 (Oxford strain). For
      vancomycin-susceptible and high-level vancomycin-resistant strains, 93-96% and 96
      99% of reports respectively were correct. For the low-level vancomycin-resistant
      strains, only 50-54% of reports were correct. Participants using a 5 micrograms
      vancomycin disc reported proportionally more of the low-level resistant strains
      correctly than those using 10, 20, 25, 30 or 100 micrograms discs. Participants
      not using controls were proportionally more likely to report the low-level
      resistant strains as susceptible than those using an enterococcus or S. aureus
      NCTC 6571 as a control. For the high-level gentamicin-resistant (HLGR) strains,
      96-98% of reports were correct. Depending on the strain, between 12% and 41% of
      participants also reported high-level resistance for the strains which were not
      HLGR. Those using low-content discs (< or = 30 micrograms) and breakpoint or MIC
      methods were more likely to report strains which were not HLGR as HLGR than those
      using high-content discs. Those using an enterococcus as a control were less
      likely to report strains which were not HLGR as HLGR than those using either S.
      aureus NCTC 6571 or E. coli as a control and those not using a control.

PMID- 8262863
TI  - Activity of imipenem, third-generation cephalosporins, aztreonam and
      ciprofloxacin against multi-resistant gram-negative bacilli isolated from Chilean
      hospitals.
AB  - The activity of imipenem against nosocomial strains of Klebsiella pneumoniae,
      Pseudomonas aeruginosa, Acinetobacter spp. and methicillin-resistant
      Staphylococcus aureus resistant to some third-generation cephalosporins,
      aztreonam, or ciprofloxacin was assessed. These strains represent the most
      prevalent multi-resistant nosocomial microorganisms in Chile since they were
      isolated from clinical specimens in 11 Chilean hospitals. A high proportion of
      the strains were resistant to several beta-lactams, yet all strains of K.
      pneumoniae and Acinetobacter spp. were susceptible to imipenem; resistance was
      exhibited by only one strain of P. aeruginosa and 16 strains of S. aureus.
      Synergy between cefotaxime and clavulanic acid was found in almost all strains of
      K. pneumoniae, suggesting the presence of plasmid-coded beta-lactamases, probably
      with extended-spectrum activity. Killing A. baumannii by imipenem was rapid, but
      slower for P. aeruginosa. Killing of K. pneumoniae was also somewhat slower
      despite the lower MIC of imipenem for this strain. Bactericidal activity was even
      slower against one strain of methicillin-resistant S. aureus. These results
      suggest that imipenem would be an adequate alternative to other broad-spectrum
      agents in the treatment of infections due to nosocomial multi-resistant Gram
      negative bacilli.

PMID- 8262864
TI  - In-vitro evaluation of the four beta-lactamase inhibitors: BRL42715, clavulanic
      acid, sulbactam, and tazobactam.
AB  - The in-vitro synergic activities of BRL42715, a new beta-lactamase inhibitor,
      clavulanic acid, sulbactam, and tazobactam combined with ampicillin,
      piperacillin, cephalothin, or cefoperazone were tested against various bacteria
      producing known types of beta-lactamase. BRL42715 showed the best synergistic
      activity among the inhibitors tested against strains producing penicillinases of
      type I, II, III, V, and that from Klebsiella pneumoniae, cephalosporinases, and
      oxyiminocephalosporinases (except that from Klebsiella oxytoca). Clavulanic acid
      combined with the beta-lactams tested showed the best synergic activity of the
      inhibitors against strains producing type IV penicillinase and
      oxyiminocephalosporinase from K. oxytoca. The 50% inhibitory doses of BRL42715
      were superior to those of clavulanic acid against various types of beta
      lactamases except for type IV penicillinase and the oxyiminocephalosporinase from
      K. oxytoca. The inhibitory activity of BRL42715 against cephalosporinases from
      various bacteria was 10(4) to 10(6)-fold greater than that of clavulanic acid.
      The synergic effects of BRL42715 and clavulanic acid on the activity of
      piperacillin were compared against six clinical isolates of bacteria resistant to
      piperacillin. The synergic activity of BRL42715 was greater than that of
      clavulanic acid in all six isolates.

PMID- 8262865
TI  - Behaviour of beta-lactamase-positive and -negative Staphylococcus aureus isolates
      in susceptibility tests with piperacillin/tazobactam and other beta-lactam/beta
      lactamase inhibitor combinations.
AB  - beta-Lactamase production protects Staphylococcus aureus against piperacillin and
      amoxycillin. Tazobactam and clavulanate inhibit the enzyme, but beta-lactamase
      producers remained substantially less susceptible than non-producers to
      piperacillin/tazobactam and co-amoxiclav in disc tests. These observations
      reflected the fact the inhibition zones for beta-lactamase non-producers expanded
      with time, as bacterial growth was killed by the diffusing antibiotic, whereas
      those for enzyme producers maintained a constant diameter after they first became
      discernible, indicating equilibrium between diffusion and destruction of the
      antibiotic. The antibiotic destruction required for this equilibrium depended on
      biomass formation, which was apparent from the luxuriant growth on beta-lactamase
      producers around the inhibition zone edges, and on beta-lactamase induction,
      which was demonstrable when S. aureus cultures were exposed to discs containing
      tazobactam alone. beta-Lactamase-related effects on the activity of inhibitor
      combinations were apparent also in MIC tests, but only when these were performed
      with large inocula. Thus, the MICs of piperacillin or amoxycillin with tazobactam
      or clavulanate were only two- to four-fold higher for beta-lactamase producers
      than non-producers at low inocula (10(4) cfu), but this differential increased to
      6- to 16-fold at high inocula (10(6) cfu). Inoculum effects were greater for
      tazobactam combinations than for clavulanate combinations, irrespective of the
      partner penicillin. These beta-lactamase-related inhibition zone differentials
      and inoculum effects for the inhibitor combinations resemble previous
      observations for first-generation cephalosporins, notably cephazolin and
      cephaloridine. Their significance for the latter compounds has occasioned long
      debate.

PMID- 8262866
TI  - In-vitro activity of three new fluoroquinolones and synergy with ansamycins
      against Mycobacterium leprae.
AB  - The efficacy of three fluorinated quinolones, clinafloxacin (PD 127391),
      sparfloxacin (PD 131501) and PD 131628, either alone or in combination with
      rifampicin/rifabutin, against Mycobacterium leprae was evaluated in vitro using
      two biochemical parameters to measure the metabolic activity of the organism.
      Clinafloxacin was found to be most effective with an MIC of 0.75 mg/L, followed
      by sparfloxacin (MIC 1.5 mg/L) and PD131628 (MIC 3.0 mg/L). When combined with
      rifampicin each of the three quinolones were additive to the activity. However,
      when combined with rifabutin, both clinafloxacin and sparfloxacin demonstrated
      pronounced synergic activity. Incorporation of clinafloxacin and rifabutin in a
      multi-drug therapy regimen is suggested.

PMID- 8262867
TI  - Efficacy of cefoperazone in combination with sulbactam in experimental
      Staphylococcus aureus endocarditis in rabbits.
AB  - The activity of cefoperazone with and without sulbactam was studied in vitro and
      in vivo against strains of methicillin-resistant and methicillin-susceptible
      Staphylococcus aureus. Cefoperazone with or without sulbactam was inactive in
      vitro against the methicillin-resistant strain and was bound by penicillin
      binding protein 2a with an IC50 of 190 mg/L (the concentration that reduced radio
      labelling with 3H-penicillin by 50%). Cefoperazone was hydrolysed by beta
      lactamase in vitro but sulbactam improved cefoperazone activity in a rabbit model
      of aortic valve endocarditis caused by a beta-lactamase producing methicillin
      susceptible strain.

PMID- 8262868
TI  - Effect of hydroxypropyl-beta-cyclodextrin on efficacy of oral itraconazole in
      disseminated murine cryptococcosis.
AB  - The therapeutic efficacy of itraconazole solubilized in either the commonly used
      vehicle, polyethylene-glycol-200 (PEG) or hydroxypropyl beta-cyclodextrin was
      compared in a murine model of disseminated cryptococcosis. Itraconazole at doses
      of up to 120 mg/kg/day solubilized in PEG were found not to be effective.
      However, itraconazole at doses > or = 30 mg/kg/day solubilized in hydroxypropyl
      beta-cyclodextrin markedly prolonged survival and a relationship between dose and
      survival was seen.

PMID- 8262869
TI  - Therapeutic efficacy of a liposomal formulation of amphotericin B (AmBisome)
      against murine blastomycosis.
AB  - The efficacy of a liposomal amphotericin B preparation (AmBisome) and a
      deoxycholate suspension (Fungizone) were compared in a pulmonary model of murine
      blastomycosis. Male, four-week-old CD-1 mice were infected intranasally with
      19,400 or 27,450 cfu of viable Blastomyces dermatitidis yeasts and intravenous
      therapy begun 4 days later. Groups of ten mice were given various dosages of
      Fungizone or AmBisome or were untreated. All treatments were given 3 times per
      week for 2 weeks. Deaths were recorded over 49 days and the number of viable
      yeasts in the lungs of survivors quantitated by viable counting. Therapy with 1.0
      mg/kg/dose of Fungizone or 1.0, 3.0, 5.0, 7.5 or 20.0 mg/kg/dose of AmBisome were
      equivalent and prolonged survival over controls and lower dosages of each drug.
      No acute or chronic toxicities were observed with any regimen. Quantitation of
      residual numbers of yeasts in the lung showed that 70-100% of mice given 7.5
      mg/kg or greater of AmBisome were free of infection and were superior to other
      regimens. At equivalent 1.0 mg/kg dosages Fungizone was superior to AmBisome.
      Although AmBisome was three-fold less active than Fungizone on a dosage basis,
      higher curative doses could be given that were not toxic. These data indicate
      that AmBisome should be further tested in other models and in clinical trials.

PMID- 8262870
TI  - Correlation between macrolide lung pharmacokinetics and therapeutic efficacy in a
      mouse model of pneumococcal pneumonia.
AB  - The correlation between the pharmacokinetics of erythromycin, roxithromycin,
      clarithromycin, spiramycin and azithromycin and their efficacy was investigated
      in two pneumococcal pneumonia models. Female Swiss and C57B1/6 mice were infected
      with Streptococcus pneumoniae strain P4241 by the intratracheal per oral route.
      This virulent strain produces acute pneumonia with death within 3-4 days (Swiss
      mice), or subacute pneumonia with death within 10 days (C57B1/6 mice) in
      untreated mice and the outcome of the disease is closely related to progressive
      weight loss. Swiss mice received three doses of each macrolide 50 mg/kg bd
      beginning 18 h post-infection. C57B1/6 mice received three doses of each
      macrolide 25 mg/kg, bd (except azithromycin was 12.5 mg/kg bd) beginning 48 h
      post-infection. Cure rates were evaluated on the basis of body weight variations
      recorded daily after the end of treatment. Pharmacokinetic parameters were
      determined in infected and non-infected mice after a single dose of each
      macrolide 50 mg/kg sc. The pharmacokinetics of azithromycin was also determined
      in leucopenic Swiss mice. We observed a hierarchy of in-vivo efficacy as follows:
      azithromycin > spiramycin = clarithromycin > roxithromycin = erythromycin which
      did not correlate with in-vitro MIC or MBC. The same hierarchy was found in terms
      of the lung T1/2. Lung T1/2s of macrolides could thus be predictive of their
      efficacy in respiratory tract infections. A reduced tissue AUC of azithromycin
      was seen in leucopenic mice suggesting leucocytes may help transport macrolides
      to sites of infection.

PMID- 8262871
TI  - Comparative pharmacokinetics and amoebicidal activity of metronidazole and
      satranidazole in the golden hamster, Mesocricetus auratus.
AB  - The pharmacokinetic properties of metronidazole and satranidazole were studied in
      the golden hamster (Mesocricetus auratus), at a dose of 80 mg/kg po. Blood and
      liver samples were collected at frequent time intervals and assayed for
      metronidazole and satranidazole by HPLC. Satranidazole exhibited significantly
      higher plasma concentrations than metronidazole at 1 and 2 h post-dose, but the
      comparative Cmax values were not significantly different. The satranidazole
      plasma elimination half-life of 1.01 h was significantly shorter than the
      corresponding metronidazole half-life of 3.62 h. The comparative liver
      pharmacokinetic parameters Cmax, Tmax and T1/2 did not differ significantly.
      Satranidazole however exhibited significantly higher liver concentrations at 1 h
      post-dose and Cmax and AUC0-infinity values were approximately 35% higher. The in
      vivo amoebicidal activity of both compounds was evaluated in the acute hamster
      hepatic model of amoebiasis. Both metronidazole and satranidazole were
      administered as single graded doses po, and their dose-response profiles were
      characterized. Satranidazole demonstrated significantly greater amoebicidal
      activity than metronidazole with an ED50 value of 19.5 mg/kg, compared to an ED50
      value of 45 mg/kg for metronidazole. These data suggest that higher plasma and
      liver concentrations of satranidazole and greater intrinsic potency probably
      contribute to superior amoebicidal activity in the hamster model of hepatic
      infection.

PMID- 8262873
TI  - National and international aspects of susceptibility testing.

PMID- 8262872
TI  - Comparison of imipenem/cilastatin with the combination of aztreonam and
      clindamycin in the treatment of intra-abdominal infections.
AB  - The clinical safety and efficacy of imipenem/cilastatin in the treatment of intra
      abdominal infections was compared with the combination of aztreonam and
      clindamycin in a randomized prospective trial. The severity of illness was
      determined by means of the Apache II score and a fixed outcome reporting scheme
      was used. One hundred and four patients were entered into the study, of whom 80
      were evaluable. Forty-two patients were treated with imipenem/cilastatin (500 +
      500 mg qds) and 38 with aztreonam (600 tds) and clindamycin (1000 mg tds). The
      study groups were comparable for age and sex. The imipenem/cilastatin group
      differed from the aztreonam and clindamycin group in having significantly more
      patients with the diagnosis of acute appendicitis (P < 0.01) and a significantly
      lower mean Apache score (P < 0.05). The predominate microorganisms isolated in
      both groups were Escherichia coli and Bacteroides fragilis. Treatment with
      imipenem/cilastatin proved successful in 71% and failed in 24%, and initial
      success only was seen in 5%. The numbers in the group treated with aztreonam and
      clindamycin were 64%, 29% and 7% respectively. Severity of illness, as measured
      by Apache II score, had no influence on the study outcome. Imipenem/cilastatin as
      well as the combination of aztreonam and clindamycin were effective in the
      treatment of abdominal infections and no major adverse reactions were seen.

PMID- 8262874
TI  - Origins of chemotherapy.

PMID- 8262875
TI  - Antimicrobial prophylaxis in surgery: microbiological factors.

PMID- 8262876
TI  - The postantibiotic effect of clarithromycin and its major human metabolite, 14
      hydroxy clarithromycin.

PMID- 8262877
TI  - Occurrence of drug resistance in Shigella species isolated from patients with
      diarrhoea in Bangladesh.

PMID- 8262878
TI  - Uncomplicated bereavement.
AB  - BACKGROUND: This paper evaluates the validity of the distinction between the
      depressive syndrome associated with uncomplicated bereavement and major
      depression by following the course, associated symptoms, and impairment
      associated with depressive episodes occurring in bereaved widows and widowers.
      METHODS: Two hundred fifty-nine widows/widowers were interviewed and completed
      the San Diego Widowhood Questionnaire at 2, 13, and 25 months after the deaths of
      their spouses. Subjects were diagnosed as depressed or not depressed on the basis
      of DSM-III-R criteria. RESULTS: Fifty-nine (23%) of subjects met symptomatic
      criteria for a major depressive syndrome at 2 months. Because of the close
      proximity to the death, the symptoms in these 59 subjects were considered to
      represent "uncomplicated bereavement" rather than major depression. Compared with
      widows/widowers who did not manifest an early depressive syndrome, the
      "depressed" group was more likely to have past or family histories of major
      depression, present treatment with antidepressant medication, feelings of
      worthlessness and suicidal ideation, poor health and job satisfaction, and major
      depression 1 and 2 years later. CONCLUSION: When a full depressive syndrome is
      present soon after the death of a spouse, the symptoms may often be prolonged and
      associated with substantial morbidity. We recommend that future
      conceptualizations of uncomplicated bereavement exclude persons with major
      depressive episodes.

PMID- 8262879
TI  - Obsessive compulsive disorder with psychotic features.
AB  - BACKGROUND: The purpose of this study was to systematically identify and
      characterize the demographic and clinical features of patients with obsessive
      compulsive disorder (OCD) and psychotic symptoms. METHODS: From a total of 475
      patients with DSM-III-R OCD evaluated and/or treated in an outpatient OCD clinic,
      67 patients (14%) were identified as having psychotic symptoms in addition to
      OCD. Psychotic symptoms were defined as hallucinations, delusions, and/or thought
      disorder. Clinical and demographic data on these probands were collected from
      semistructured interviews and compared with data collected on the nonpsychotic
      OCD probands. RESULTS: We identified 27 (6%) of 475 probands with DSM-III-R OCD
      whose only psychotic symptom was lack of insight and high conviction about the
      reasonableness of the obsessions ("OCD without insight"). The remainder of the
      patients with psychotic symptoms and OCD met criteria for distinct DSM-III-R
      psychotic disorders as well as OCD: 18 probands (4%) had OCD and schizophrenia, 8
      probands (2%) had OCD and delusional disorder. Fourteen patients (3%) met
      criteria for both OCD and schizotypal personality disorder. Compared with the OCD
      patients without psychosis, probands with OCD and psychotic features were more
      likely to be male, be single, have a deteriorative course, and have had their
      first professional contact at a younger age. The data suggest that these
      differences were largely due to those patients with OCD and schizophrenia
      spectrum disorders and not those probands whose only psychotic symptom was
      complete conviction and lack of insight about their obsessions. CONCLUSION: There
      appears to be considerable heterogeneity in the clinical features of OCD patients
      who also have psychotic symptoms. The implications of these findings for
      understanding delusional states and for diagnostic classification are discussed.

PMID- 8262880
TI  - Divalproex sodium in the treatment of refractory affective disorders.
AB  - BACKGROUND: Anticonvulsants have been shown to be effective in many patients with
      psychiatric disorders, especially those with bipolar affective disorder. We
      present our clinical experience with divalproex sodium in the treatment of 63
      patients with a variety of affective disorders that had proved refractory to
      conventional pharmacotherapy. METHOD: We reviewed the charts of 63 patients
      diagnosed as bipolar I (35 patients), bipolar II (23 patients), or
      schizoaffective, bipolar type (5 patients). Twelve patients who appeared to have
      recurrent unipolar depression had a retrospectively recognized history of "covert
      cycling," with brief periods of socially acceptable hypomania occurring between
      depressive episodes. Prior to treatment with divalproex, 45 patients had been
      classified as treatment failures with lithium, 29 patients had been classified as
      treatment failures with carbamazepine, and 35 patients had also failed on a
      combination of lithium and carbamazepine. Divalproex was given to these patients
      and titrated to achieve blood levels in the range of 50 to 100 mg/L. RESULTS:
      Forty-seven (75%) of the 63 patients responded positively to the addition of
      divalproex to their regimens. Of 45 patients who had failed to respond to
      lithium, 38 (84%) responded when divalproex was added. Of 29 patients who had
      failed to respond to carbamazepine, 20 (69%) responded when divalproex was added.
      Of 26 rapid-cycling patients, 21 (81%) responded to the addition of divalproex.
      Side effects required drug withdrawal in 9 patients (14%). CONCLUSION: The
      results confirm previous findings that both mania and rapid mood cycling may
      respond to a pharmacologic regimen that includes divalproex. Many patients who
      appear to have recurrent, major unipolar depression may actually be convert
      cyclers who will respond to divalproex, sometimes in combination with an
      antidepressant medication.

PMID- 8262881
TI  - Body dysmorphic disorder: does it have a psychotic subtype?
AB  - BACKGROUND: Although body dysmorphic disorder (BDD) is classified in DSM-III-R as
      a nonpsychotic somatoform disorder, controversy exists as to whether BDD can
      present with psychotic features. If it can, this raises the possibility that its
      DSM-III-R psychotic counterpart-delusional disorder, somatic type--may not be a
      separate disorder. The purpose of this study was to determine whether patients
      with nonpsychotic BDD (defined according to DSM-III-R criteria, i.e., with
      maintenance of some insight) were different from patients with psychotic BDD
      (those whose preoccupation was without insight and of delusional intensity).
      METHOD: Fifty consecutive patients meeting DSM-III-R criteria A and C for BDD
      were assessed with a semistructured interview and the Structured Clinical
      Interview for DSM-III-R (SCID). Family histories of psychiatric disorders were
      blindly assessed. The 24 patients with nonpsychotic BDD were compared with the 26
      patients with psychotic BDD with respect to demographics, phenomenology, course
      of illness, associated features, comorbid psychiatric disorders, family history,
      and treatment response. RESULTS: Patients with psychotic BDD displayed a
      significantly higher rate of lifetime DSM-III-R psychotic disorder diagnoses than
      patients with nonpsychotic BDD. However, the two groups did not differ
      significantly on most other variables examined. For instance, both psychotic and
      nonpsychotic patients displayed significant morbidity; high comorbidity with
      mood, anxiety, and psychoactive substance use disorders; and apparent
      preferential response to serotonin reuptake inhibitors rather than to non
      serotonin reuptake blocking antidepressants or antipsychotics. CONCLUSION: Body
      dysmorphic disorder may have a closely related psychotic subtype that
      significantly overlaps with, or may even be the same disorder as, the BDD variant
      of delusional disorder, somatic type. Inclusion of a psychotic subtype for BDD
      should be considered for future editions of DSM.

PMID- 8262882
TI  - More on nonphysician prescribers.

PMID- 8262883
TI  - Converting from Lithobid to other lithium preparations.

PMID- 8262884
TI  - EEG in psychiatry.

PMID- 8262886
TI  - Issues in the clinical use of alprazolam.

PMID- 8262885
TI  - Obsessive compulsive disorder manifesting as demonic attack.

PMID- 8262888
TI  - A comparison of the safety and efficacy of alprazolam versus other agents in the
      treatment of anxiety, panic, and depression: a review of the literature.
AB  - A review of the worldwide published literature was conducted to assess the
      efficacy and safety of alprazolam for the treatment of anxiety disorders, panic
      disorder, and depression in comparison with those of other active drugs
      (including other benzodiazepines and antidepressant medications). In all, a total
      of 8878 patients participated in the 84 active-drug-controlled studies that were
      reviewed: 3574 were treated with alprazolam, 3666 were treated with another
      active drug, and 1638 were treated with placebo. Two general findings emerged:
      (1) Alprazolam demonstrates efficacy for the treatment of anxiety disorders,
      panic disorder, and depression in the large majority of studies; for these
      illnesses, it appeared equal in efficacy to the active agents with which it was
      compared. (2) Medical events, such as depression, suicidality,
      hostility/aggression, mania/psychosis, abuse, withdrawal reactions, and seizures,
      were reported infrequently or not at all for alprazolam and the comparator drugs;
      there were no marked differences between drug classes in the frequencies of these
      events.

PMID- 8262887
TI  - Medication discontinuation in panic disorder.
AB  - This paper addresses current issues associated with medication discontinuation in
      panic disorder, with specific focus on one of the most frequently used medication
      classes for this indication, the benzodiazepines. The majority of patients, when
      slowly tapered, are able to discontinue the benzodiazepines without a great deal
      of difficulty, particularly after short-term therapy. Patients treated with long
      term therapy at high therapeutic doses may experience greater difficulty with
      discontinuation. If patients are adequately prepared and if discontinuation is
      conducted slowly and gradually, discontinuation symptoms, if they occur, are
      transient, mild to moderate, and generally tolerable. However, return of the
      original condition (relapse) during discontinuation can greatly complicate
      clinical management.

PMID- 8262889
TI  - Alprazolam pharmacokinetics, metabolism, and plasma levels: clinical
      implications.
AB  - The triazolobenzodiazepine alprazolam is biotransformed by hepatic microsomal
      oxidation, yielding two hydroxylated metabolites (4-hydroxy- and a-hydroxy
      alprazolam) as the principal metabolic products. Both metabolites have lower
      benzodiazepine receptor affinity than the parent compound and at steady state
      appear in plasma at concentrations considerably lower than intact alprazolam.
      Thus, clinical activity during treatment with alprazolam is essentially entirely
      attributable to intact alprazolam. The cytochrome P450 IIIA subfamily appears to
      mediate alprazolam metabolism in humans. This cytochrome subfamily is not subject
      to variation due to genetic polymorphism. Ketoconazole, cimetidine, macrolide
      antibiotics, and serotonin-reuptake-inhibitor antidepressants impair alprazolam
      biotransformation in vitro. Reduced clearance of alprazolam in vivo has been
      demonstrated for drugs in this group that have been studied in humans; for those
      not yet studied, impaired alprazolam clearance should be anticipated during
      coadministration. Studies of plasma alprazolam concentration versus clinical
      response during short-term treatment of panic disorder indicate that therapeutic
      response at steady-state plasma levels of 20 to 40 ng/mL is significantly greater
      than at levels less than 20 ng/mL. Substantial additional benefit from plasma
      levels greater than 40 ng/mL is not consistently demonstrated. However, side
      effects attributable to benzodiazepine agonist activity (e.g., drowsiness,
      sedation) increase in frequency with increasing steady-state plasma levels.
      Concentration-response data indicate that monitoring of alprazolam plasma levels
      can be of considerable clinical value during treatment of panic disorder.

PMID- 8262890
TI  - Adverse behavioral events reported in patients taking alprazolam and other
      benzodiazepines.
AB  - A review of the published case reports of adverse behavioral episodes or
      unexpected psychopathology in patients taking benzodiazepines was undertaken in
      an attempt to determine if these adverse or unexpected events are more likely to
      occur with alprazolam when compared with other currently marketed
      benzodiazepines. Adverse behavioral phenomena and unexpected psychopathology were
      divided into the following categories: (1) anger or violence, (2) impulsive,
      suicidal, or self-harming behavior, (3) depression, (4) mania, (5) schizophrenia,
      (6) withdrawal syndromes and (7) physical dependence and abuse liability. It is
      difficult to draw conclusions from this literature because of the limitations of
      spontaneously reported cases and the lack of epidemiologic studies. Despite these
      limitations, it appears that some differences between alprazolam and older
      benzodiazepines may exist. The older benzodiazepines are more commonly reported
      to have adverse events than alprazolam (with the exception of mania or
      hypomania). On the other hand, worsening in post-traumatic stress disorder and an
      increase in impulsive behavior in patients with borderline personality disorder
      have only been reported in patients receiving alprazolam. This is probably
      explained by the fact that only alprazolam has been used to any great extent in
      these conditions.

PMID- 8262891
TI  - Alprazolam and benzodiazepine dependence.
AB  - The incidence of nonmedical use of alprazolam is very low relative to its
      widespread legitimate medical use; in fact, given the millions of patients who
      have received this medication, the incidence is remarkably small. In particular,
      among patients with anxiety disorders, dependence does not appear to be a
      clinically important problem. Alprazolam abuse and dependence represent only a
      small fraction of the large and serious nonmedical use problem in the United
      States, and when they occur, are among individuals who abuse other drugs. For
      example, a serious problem of alprazolam abuse may exist among patients in
      methadone maintenance treatment. A similar problem exists with diazepam. Alcohol
      abusers and alcohol-dependent individuals are another group among whom concern
      about benzodiazepine and alprazolam abuse exists. However, more and better
      information about the extent and nature of this use is needed. Many patients with
      alcohol or drug abuse also have anxiety disorders for whom effective
      pharmacotherapy may be needed. In the interim, caution but not prohibition to use
      should prevail in prescribing alprazolam to such patients. To the extent that
      nonmedical alprazolam use exists, evidence suggests that the vast majority of
      such use is the consequence of the inappropriate prescribing of the medication by
      a small number of physicians. One way to reduce the inappropriate use of
      benzodiazepines in methadone programs is to drug test the methadone-maintenance
      patients and to link positive urine tests to contingency-management strategies.
      The available data provide some support to the idea that alprazolam and diazepam
      have more abuse liability than other benzodiazepines.

PMID- 8262892
TI  - Alprazolam and depression: a review of risks and benefits.
AB  - Therapeutic efficacy for depression and panic disorder has been demonstrated with
      the triazolobenzodiazepine alprazolam. However, potentially serious adverse
      events, including depression and suicide attempts, have been reported in patients
      taking this medication. In this paper, reports addressing the association between
      each of these two events and benzodiazepine use in general and, more
      specifically, alprazolam use, are reviewed. We conclude that while these adverse
      events do occur in patients taking alprazolam, the causal relationship remains
      unclear and requires further study. Fortunately, these events are observed only
      rarely, so the prudent clinician may continue to safely prescribe this useful
      medication.

PMID- 8262893
TI  - Memory, benzodiazepines, and anxiety: integration of theoretical and clinical
      perspectives.
AB  - The benzodiazepines have been reported to cause anterograde amnestic effects.
      These impairments are likely mediated through the GABAA receptor complex, which
      contains the benzodiazepine receptor binding site. This GABAA receptor site is
      also believed to be the locus of the anxiolytic effects of the drugs as well, and
      recent research findings suggest that the anxiolytic and amnestic properties of
      the benzodiazepines may be functionally linked. Normal human memory function is
      extremely complex and requires the smooth integration of multiple aspects of
      cognition. On the basis of neuropsychological testing, the processes of memory
      have been divided into a variety of functions or stores that are interrelated,
      yet distinct. The amnestic effects of the benzodiazepines have been extensively
      studied within the context of this conceptual framework. Studies to date have
      shown that the memory deficits produced by the drugs are relatively selective and
      are primarily caused by impairments in the acquisition of newly learned
      information into long-term episodic storage. Benzodiazepines may impair other
      aspects of memory as well, but findings across studies have been inconsistent.
      The drugs clearly do not impair the recall of previously learned information,
      unlike anticholinergic drugs with amnestic effects, such as scopolamine. The
      amnestic effects of the benzodiazepines are dose-dependent, and can be predicted
      by pharmacokinetic/pharmacodynamic variables. In addition, multiple clinical
      factors may influence the likelihood of memory impairments. The amnestic effects
      of alprazolam are consistent with the drug effects of the benzodiazepines as a
      group.

PMID- 8262895
TI  - The alpha subunit of ATP synthase (F0F1): the Lys-175 and Thr-176 residues in the
      conserved sequence (Gly-X-X-X-X-Gly-Lys-Thr/Ser) are located in the domain
      required for stable subunit-subunit interaction.
AB  - The sequence (Gly-X-X-X-X-Gly-Lys-Thr/Ser) is conserved in nucleotide binding
      proteins including the alpha and beta subunits of the ATP synthase. Various
      mutations were introduced in the alpha Lys-175 and alpha Thr-176 residues in the
      sequence (Gly-Asp-Arg-Gln-Thr-Gly-Lys-Thr, residues 169-176) of the Escherichia
      coli ATP synthase alpha subunit. Surprisingly, single amino acid substitutions
      drastically affected the subunit assembly of the enzyme. The entire enzyme
      assembly was lost by alpha Lys-175-->Phe (or Trp) or alpha Thr-176-->Phe (or Tyr)
      mutation. Other mutants had similar (alpha His-175, alpha Ser-175, alpha Gly-175,
      alpha Ser-176, and alpha His-176 mutants) or lower (alpha Ala-176, alpha Cys-176,
      alpha Leu-176, and alpha Val-176 mutants) effects on assembly of the active
      enzyme compared with that of the wild-type. However, all these mutant enzymes
      except the alpha Ser-176 enzyme showed enhanced cold sensitivities and reduced
      stabilities at high temperature. Mutant enzymes such as alpha Gly-175 and alpha
      His-176 showed low multi-site (steady state) catalysis, possibly due to loss of
      proper subunit-subunit interactions. These results suggest that the alpha Lys-175
      and alpha Thr-176 residues are not absolutely essential for catalysis, but that
      they, or possibly the entire conserved sequence, are located in the key domain
      for the subunit-subunit interactions essential for enzyme stability and steady
      state activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262894
TI  - Requirement of brain extract for the activity of brain calmodulin-dependent
      protein kinase IV expressed in Escherichia coli.
AB  - Calmodulin-dependent protein kinase IV (CaM-kinase IV) is a Ca(2+)-responsive
      multifunctional protein kinase which occurs abundantly in the brain. When cDNA
      for rat brain CaM-kinase IV was expressed in Escherichia coli, the enzyme was
      produced in a good yield, but it did not show significant activity. The inactive
      recombinant CaM-kinase IV was phosphorylated and became highly active on
      incubation with a rat brain extract in the presence of both Ca2+/calmodulin and
      ATP/Mg2+. The recombinant CaM-kinase IV-activating activity in brain was one to
      two orders of magnitude higher than that in the other tissues examined. These
      observations suggest that CaM-kinase IV may undergo a posttranslational
      modification, probably Ca2+/calmodulin-dependent phosphorylation by CaM-kinase IV
      kinase, before exhibiting activity in the central nervous system.

PMID- 8262897
TI  - Reannealing of beta-actinin-severed actin filaments by troponin and tropomyosin.
AB  - During a survey of actin pointed end-capping protein in salt extracts of rabbit
      skeletal muscle, it was found that native tropomyosin (troponin-tropomyosin
      complex) inhibited the seed activity of beta-actinin-capped actin filaments for
      actin polymerization. It turned out that beta-actinin-capped actin fragments
      reannealed to form long filaments resulting in the decrease in seed numbers in
      the presence of troponin and tropomyosin. It appears that the reannealing of
      actin filaments was due to release of beta-actinin from the actin filaments by
      troponin and tropomyosin. Either troponin or tropomyosin alone was not effective
      at all. Addition of an excess amount of beta-actinin did not prevent the
      reannealing of beta-actinin-capped actin filaments in the presence of troponin
      and tropomyosin.

PMID- 8262896
TI  - Substrate specificity of protein kinase C studied with peptides containing D
      amino acid residues.
AB  - A set of stereoisomeric nonapeptides KRPSQRAKY with one, two, or all L-amino acid
      residues replaced by the corresponding D-amino acids, and two analogs with L- and
      D-threonine instead of serine, were synthesized and tested as substrates for
      protein kinase C. All of the peptides were phosphorylated by the enzyme. The
      maximal rate of the reaction with the all-D peptide was more than one order of
      magnitude lower than that for all-L peptide with serine. The same applied to the
      peptides with D-Ser or with D-Arg in position +2 with respect to Ser. The Km
      values for the peptides containing one D-amino acid were close to that for the
      prototype peptide (53 microM). On the other hand, when two or more D-amino acids
      were present, the Km value increased considerably. Replacement of serine by
      threonine also reduced the phosphorylation rate and increased the Km values. One
      can conclude that the stereospecificity of protein kinase C is much less
      pronounced than that of protein kinase A, which is in agreement with the less
      clearly pronounced substrate specificity of the former enzyme.

PMID- 8262898
TI  - Characterization of ganglioside expression in human melanoma cells: immunological
      and biochemical analysis.
AB  - The expression of N-glycolylneuraminic acid (NeuGc)-containing gangliosides in
      human melanoma cells grown both in culture and as xenografts in athymic (nu/nu)
      mice was analyzed extensively with specific mouse monoclonal antibodies (MAbs).
      Three MAbs (GMR8, GMR14, and GMR3) specific for GM3(NeuGc), GM2(NeuGc), and
      GD3(NeuGc-NeuGc-), respectively, were used. Significant differences were observed
      in the ganglioside compositions between the cultured cells in vitro and the
      tumors grown in vivo. The major difference was that the cells cultured in serum
      free medium did not express any NeuGc-containing gangliosides, whereas those
      grown in nude mice expressed a number of NeuGc-containing gangliosides, namely
      GM3(NeuGc), GM2(NeuGc), GD3(NeuAc-NeuGc-), GD3(NeuGc-NeuAc-), and GD3(NeuGc-NeuGc
      ). The structures of these gangliosides were also determined chemically. No
      activity of CMP-NeuAc hydroxylase was demonstrated either in the melanoma cells
      cultured in vitro or in those grown in nude mice, suggesting that these cells
      incorporated NeuGc-containing glycoconjugates from the mouse sera and converted
      them to other NeuGc-containing gangliosides. The mouse sera contained only
      GM2(NeuGc), but not the other NeuGc-containing gangliosides or any NeuAc
      containing gangliosides.

PMID- 8262900
TI  - Uncoupling of ATP splitting from Ca(2+)-transport in Ca(2+)-transporting ATPase
      of the sarcoplasmic reticulum as a result of modification by N-(3
      pyrene)maleimide: activation of a channel with a specificity for alkaline earth
      metal ions.
AB  - The sarcoplasmic reticulum (SR) membranes of rabbit skeletal muscle were allowed
      to react with N-(3-pyrene)maleimide (PMI) at pH 7 at 30 degrees C. The Ca(2+)
      transporting activity of the SR membranes was reduced to 20% when PMI was bound
      to the extent of 1 mol/mol of Ca(2+)-transporting ATPase. The ATPase and the E-P
      forming activities were not affected by the binding of PMI up to 2 mol/mol
      ATPase, indicating that PMI somehow uncoupled Ca(2+)-transport from ATP
      splitting. Permeability of the SR membranes to Ca2+ ions was increased in
      parallel with the loss of the Ca(2+)-transporting activity. Of several components
      of the SR membranes which are reactive with PMI, the ATPase protein was the only
      one whose modification by PMI was directly related to the loss of the Ca(2+)
      transporting activity. Similar results were obtained with the light SR membrane
      fraction, which lacks the ryanodine receptor, a well-recognized Ca2+ channel.
      These results indicated that a Ca2+ channel that would have been latent or
      properly regulated in native ATPase somehow escaped from the normal control
      mechanism as a result of modification of its SH groups by PMI and went into
      runaway operation. The activated channel was specific for alkaline earth metal
      ions, so permeability to other solutes including Co2+, Ni2+, and sucrose remained
      unchanged after treatment with PMI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262899
TI  - Isolation of a subclonal cell line of PC12 transfected with dexamethasone
      regulated ras oncogene: morphological differentiation, biochemical properties,
      and tumorigenicity.
AB  - We have isolated and characterized a new subclonal cell line designated as MR31,
      which was obtained by transfection of PC12 cells with a glucocorticoid-regulated
      ras oncogene. The mRNA derived from the c-Ha-ras gene was proved to be expressed
      on exposure of the MR31 cells to dexamethasone, the highest value being attained
      at 8 h. MR31 cells rapidly extended neurite-like processes within 24 h in
      response to dexamethasone as well as nerve growth factor (NGF). The time of onset
      of neurite outgrowth induced by dexamethasone corresponded to the time when the
      highest ras mRNA level was observed. The catecholamine content of MR31 cells was
      found to be twice that of PC12 cells. A time course study on the effects of
      dexamethasone or NGF on cells showed that the former caused an increase in
      dopamine, a major catecholamine, to twofold the control level at 48 h after the
      treatment, while the latter caused a decrease in the dopamine level. These
      effects on catecholamines were almost the same in MR31 and PC12 cells. The
      acetylcholinesterase activity of MR31 cells was enhanced by both dexamethasone
      and NGF, whereas that of PC12 cells was enhanced by NGF, but not by
      dexamethasone. The changes in acetylcholinesterase activity were correlated with
      neurite outgrowth. Electron-microscopically, MR31 cells were not different from
      PC12 cells. MR31 cells exhibited extremely decreased tumorigenicity as compared
      with PC12 cells. The morphological and biochemical properties of MR31 cells
      remained constant, even after repeated passages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8262901
TI  - Molecular dynamics simulation of 1,2-dilauroyl-L-phosphatidylethanolamine binding
      to phospholipase A2: an attempt to explain the selective hydrolysis of substrate
      fatty acid ester at position 2.
AB  - To improve our understanding of why phospholipase A2 (PLA2) specifically
      catalyzes the hydrolysis of the fatty acid ester bond at position 2, not at
      position 1, of 1,2-diacyl-3-sn-phosphoglycerides, the binding of each fatty acid
      chain of 1,2-dilauroyl-L-phosphatidyl-ethanolamine (DLPE), a natural substrate,
      to bovine pancreas PLA2 was examined by molecular dynamics (MD) simulations. Two
      different binding modes were considered, i.e., the respective hydrocarbon chains
      of 1- and 2-lauroyl fatty acid esters were located at the PLA2 binding sites
      usually observed in the complex crystals (Form A2) and at the reverse sites (Form
      A1). Although the total energies of both forms fluctuated within nearly the same
      range during the 80 ps MD simulations, the binding mode of DLPE to the PLA2
      catalytic site through the coordination to Ca2+ was much more advantageous in
      Form A2 than that in Form A1; significant deviation of the Ca2+ position from its
      starting structure was observed in the MD simulation of Form A1. The result
      suggests the importance of Ca2+ in the selective recognition and catalytic
      function of PLA2 toward the 2-positioned fatty acid ester of phosphoglyceride
      substrates.

PMID- 8262902
TI  - Electron-transferring flavoprotein has an AMP-binding site in addition to the FAD
      binding site.
AB  - Mammalian electron-transferring flavoprotein (ETF) has been reported to consist
      of two non-identical subunits and one FAD. The present paper shows that ETF
      purified from pig kidney contains one more molecule, an AMP. ETF was denatured by
      guanidine hydrochloride and ultrafiltered for the purpose of removing proteins.
      The filtrate was analyzed by reverse-phase chromatography. Two peaks appeared on
      the chromatogram: they were identified as FAD and AMP, and their molar amounts
      were identical, indicating that ETF contains one AMP molecule. ApoETF, which was
      prepared by KBr treatment of ETF, also contains one AMP molecule. ApoETF, which
      was prepared by KBr treatment of ETF, also contain one AMP molecule. These
      results clearly demonstrate that ETF has an AMP-binding site in addition to the
      FAD-binding site. AMP-free apoETF was prepared by guanidine treatment of ETF.
      Mixing AMP-free apoETF, FAD, and AMP produced reconstituted ETF, which showed the
      same properties as native ETF. Mixing AMP-free apoETF and FAD produced AMP-free
      ETF, regardless of the coexistence of ATP or ADP: the AMP-binding site cannot
      bind FAD, ADP, or ATP. The enzymatic activity of the AMP-free ETF for electron
      transfer from substrate-reduced medium-chain acyl-CoA dehydrogenase to 2,6
      dichlorophenolindophenol was identical to that of native ETF. This indicates that
      the AMP contained in holoETF has no apparent influence on this enzymatic
      activity. A role of AMP recognized in this study is that AMP facilitates the
      formation of holoETF from AMP-free apoETF, FAD, and AMP.

PMID- 8262903
TI  - A study of the lipids and carotenoprotein in the prawn, Penaeus japonicus.
AB  - The lipid and fatty acid composition of the hepatopancreas and muscle of the
      prawn, Penaeus japonicus, were analyzed. The hepatopancreas was the main lipid
      storage organ, triglycerides and phospholipids being its major lipid components,
      while muscle contained mainly phospholipids. The fatty acid compositions of total
      lipids from the hepatopancreas and muscle were similar to those in other marine
      animals. The major fatty acids were palmitic (16:0), oleic (18:1n-9),
      eicosapentaenoic (20:5n-3), and docosahexaenoic (22:6n-3) acids. The
      monoglycerides, diglycerides, triglycerides, and cholesterol esters from the
      hepatopancreas and muscle exhibited similar fatty acid patterns, but each lipid
      fraction was characterized by a specific paraffin chain composition. A blue
      carotenoprotein (lambda max = 640 nm) containing astaxanthin was also extracted
      and purified from the hypodermis of the prawn. This blue carotenoprotein has a
      molecular weight of ca. 280,000, which is much lower to those given for other
      crustaceans. The carotenoid prosthetic group was released from the
      carotenoprotein by the addition of acetone, and showed a hypsochromic shift to
      470 nm and the characteristic shape of free ketocarotenoids. TLC, infrared
      spectroscopy, chemical reduction, spectrophotometry, and qualitative analysis by
      HPLC were used to identify the astaxanthin as a unique chromophore group of the
      blue carotenoprotein. Moreover, HPLC studies suggested all-trans-astaxanthin to
      be the main component, which was accompanied by an epimer and its cis-isomer.

PMID- 8262904
TI  - Mode of action of exo- and endo-type cellulases from Irpex lacteus in the
      hydrolysis of cellulose with different crystallinities.
AB  - The mode of action of two highly purified cellulases of exo- and endo-types from
      Irpex lacteus was investigated by using pure cellulosic substrates with different
      crystallinities derived from cellulose I. Exo-type cellulase saccharified all
      celluloses more effectively than endo-type enzyme, and the saccharification
      activities of both cellulases similarly increased with decreasing crystallinity
      of cellulose. The DP-lowering activity of exo-type cellulase remained similar for
      celluloses with higher crystallinity, while this cellulase showed a degradation
      mode resembling that of the endo-type enzyme for the substrates with lower
      crystallinity. Compared with exo-type cellulase, endo-type cellulase remarkably
      decreased the DP of cellulose with higher crystallinity, while this activity was
      abated for cellulose with lower crystallinity. Thus, the effects of both
      cellulases became similar in the degradation of amorphous substrates such as
      H3PO4-treated cellulose. Endo-type cellulase produced several kinds of
      cellooligosaccharide from all kinds of cellulose used, while the product of the
      exo-type enzyme was only cellobiose from crystalline cellulose such as cotton and
      cotton linter even after a 12-h incubation period. The results indicate that each
      cellulase shows a typical mode of action (exo or endo) for crystalline cellulose,
      but that their characteristic modes of attack may change with decreasing
      crystallinity of cellulose.

PMID- 8262905
TI  - Electron microscopic observation of cotton cellulose degradation by exo- and endo
      type cellulases from Irpex lacteus.
AB  - The interaction of two highly purified cellulases, exo- and endo-type cellulases
      from Irpex lacteus, with pure cotton and amorphous cellulose was investigated by
      electron microscopy. The morphological observations indicated that exo- and endo
      type cellulases are both strongly adsorbed on the internal microfibril of cotton
      fiber before enzymatic hydrolysis, and then initiate their action toward the
      internal cellulose microfibrils with retention of the original shape. The two
      cellulases, however, caused considerably different morphological changes in
      cotton cellulose, and each cellulase seems to degrade native cellulose with a
      distinct mode of action. In the hydrolysis of cotton with exo-type cellulase,
      deep transverse cracks were produced and they extended from the fiber surface to
      the lumen structure located inside the fibers. In contrast, it was found that
      there were no deep cracks on fibers treated with endo-type cellulase, but severe
      internal erosion and cavitation occurred along fibril or microfibril layers
      inside the fibers. Thus, the degradation of cotton by exo- and endo-type
      cellulases yielded quite different morphological patterns, while little
      difference was found for regenerated celluloses. The mode of enzymatic hydrolysis
      of cellulose shown by cellulases with different degrees of randomness (exo and
      endo types) appears to be markedly affected by the fine structure of cellulose
      fibers.

PMID- 8262906
TI  - Calcium ion dependent interaction of inorganic phosphorus compounds with
      phosphatidylcholine.
AB  - The translocation of orthophosphate, pyrophosphate, and polyphosphate into an
      organic phase was examined by means of the two-phase partition method. When the
      organic phase contained phosphatidylcholine (PtdCho), the phosphorus compounds
      translocated from the water-phase into the organic phase, depending on the
      concentrations of PtdCho and Ca2+, and the pH of the solution. Calcium ions were
      essential for the translocation. The concentration of Ca2+ necessary for the
      translocation appeared to depend on the molar concentration of the phosphorus
      compounds. Orthophosphate was translocated above pH 6.5, while pyrophosphate was
      translocated above pH 3.5. In contrast, polyphosphate was translocated in the
      whole pH range examined (pH 2.5-9.0), although approx. 9% of the total
      polyphosphate remained in the water-phase even at alkaline pH. These results
      suggest that phosphorus compounds can interact with PtdCho when the phosphorus
      compounds have formed complexes with Ca2+.

PMID- 8262907
TI  - The structure of recombinant human carboxy-terminal-truncated macrophage colony
      stimulating factor derived from mammalian cells.
AB  - The structure of recombinant human carboxy-terminal-truncated macrophage colony
      stimulating factor expressed in CHO cells was investigated. The bioactive protein
      ([-32-153]M-CSF), expressed from a nucleotide sequence that encoded a signal
      peptide of 32 amino acids and N-terminal amino acids numbers 1-153, was
      heterogeneous in terms of molecular mass, as analyzed by SDS-PAGE, because of the
      presence of N-linked sugar moieties. The primary structure of the polypeptide was
      determined by sequence analysis and amino acid analysis of the fragments obtained
      from lysylendopeptidase digests of reduced and alkylated M-CSF, and from pepsin
      digests of the intact molecule. A sugar chain was located only at Asn-122 of the
      two putative sites of N-glycosylation that were present per subunit. The
      homodimeric structure appeared to have seven disulfide bonds, formed by inter- or
      intra-molecular linkages, since there were no free thiol groups in the molecule.
      The assignment of disulfide bonds by sequence analysis using peptide fragments
      indicated the combinations of Cys7-Cys90, Cys48-Cys139, and Cys102-Cys146. Gel
      filtration analysis of Ser31[-32-153]M-CSF, in which the remaining Cys31 was
      replaced by Ser and which was expressed in COS cells, suggested that the mutein
      existed as a monomer. Our study shows that the disulfide-bond pairings of [-32
      153]M-CSF that is expressed and post-translationally modified in mammalian cells
      are identical to those of Escherichia coli-derived [3-153]M-CSF with only one
      intermolecular disulfide bond, namely, Cys31-Cys31.

PMID- 8262908
TI  - Cysteine proteinase from the eggs of the silkmoth, Bombyx mori: identification of
      a latent enzyme and characterization of activation and proteolytic processing in
      vivo and in vitro.
AB  - When an acid cysteine proteinase, which had been purified from the eggs of
      silkmoth, Bombyx mori, was incubated at pH 3.6, enzymatic activity appeared after
      a few minutes, lag period, indicating that the purified cysteine proteinase was a
      latent form. SDS-polyacrylamide gel electrophoresis showed that after the
      incubation the latent form of the enzyme (47 kDa) disappeared and the active (39
      kDa) form of the enzyme appeared, suggesting that the latent form was processed
      to the active form under acidic conditions (pH 3.6). The NH2-terminal 22-residue
      sequence of the active form was determined. The conversion of the latent form to
      the active form was completely blocked by E-64, which is a specific inhibitor of
      cysteine proteinases. The results strongly suggest that the processing might be
      autocatalytic. The latent form (47 kDa) disappeared in the silkmoth eggs during
      embryonic development and concomitantly with its disappearance, the 39-kDa form
      appeared, indicating that in vivo the enzyme is activated in a similar manner to
      that observed in in vitro experiments.

PMID- 8262909
TI  - Preparation of mouse monoclonal antibodies to okadaic acid and their binding
      activity in organic solvents.
AB  - Seven of 20 mouse monoclonal antibodies to OA, OA8-2, OA10-8, OA22-22, OA227-11,
      OA296-1, OA423-3, and OA958-2, were studied as to their binding to OA in organic
      solvents. OA423-3 (IgG1-kappa) and OA958-2 (IgG1-kappa) in 90-100% methanol
      retained their binding activities with both immobilized and free antibodies.
      Whereas OA8-2 (IgG2a-kappa), OA10-8 (IgG1-kappa), OA22-22 (IgG2a-kappa), OA227-11
      (IgG1-kappa), and OA296-1 (IgM-kappa) did not bind to OA in over 50-60% methanol.
      The results of a non-competitive inhibition assay for OA indicated that in a
      methanolic or ethanolic solution, the binding ability of immobilized OA423-3
      decreased as the concentration of each alcohol increased. The concentration of OA
      at the midpoint between the upper and lower plateaus of the inhibition curve was
      0.18 ng/ml in 0% methanol and 570 ng/ml in 100%, respectively. In 0-50% of each
      of acetone, diethyl ether, and benzene in methanol, the binding ability of OA423
      3 remained at the level in 100% methanol. OA958-2 showed similar binding
      properties to OA423-3. No relationship between the subclass of the immunoglobulin
      and the binding activity of the antibody in organic solvents was observed. These
      results indicate that the OA423-3 and OA958-2 antibodies are useful for the
      development of a new ELISA method for OA in organic solvents.

PMID- 8262910
TI  - Role of myosin in the stimulatory effect of caldesmon on the interaction between
      actin, myosin, and ATP.
AB  - We have previously shown that caldesmon at low concentrations stimulates the
      interaction between actin, myosin, and ATP, while at high concentrations it
      inhibits the interaction [Ishikawa, R., Okagaki, T., Higashi-Fujime, S., &
      Kohama, K. (1991) J. Biol. Chem. 266, 21784-21790]. When the effect of caldesmon
      at low concentrations was monitored by measuring myosin ATPase activity in the
      absence of actin, the effect was slightly but significantly stimulatory; and at
      higher concentrations no inhibitory effect was observed. Therefore, we related
      the stimulatory effect with the myosin-binding property of caldesmon. In the
      presence of actin, a low concentration of caldesmon was not enough to evince the
      stimulatory effect: myosin concentration must also be low. This is because the
      stimulatory effect was obscured when myosin concentration was elevated. Ca(2+)
      calmodulin abolished the stimulatory effect of caldesmon. However, the
      concentration of calmodulin required to abolish the stimulation was higher than
      that required to abolish the inhibition.

PMID- 8262911
TI  - Cloning of the bovine plasma selenium-dependent glutathione peroxidase (GP) cDNA
      from the ocular ciliary epithelium: expression of the plasma and cellular forms
      within the mammalian eye.
AB  - In the anterior segment of the mammalian eye, the ocular ciliary epithelium
      produces the aqueous humor, a fluid that nourishes and protects the avascular
      tissues from oxidative stress. This report details the results of a study of
      molecular cloning, sequencing, and expression of plasma glutathione peroxidase
      (GPx-P) from the bovine ocular ciliary epithelium. The bovine GPx-P cDNA contains
      an open reading frame of 226 amino acids with a calculated molecular weight of
      24,860. The corresponding amino acid sequence showed an overall identity of 88%
      with the human GPx-P, 88.5% with the rat GPx-P, and 46.4% with the cellular
      bovine glutathione peroxidase (GPx-1). The levels of GPx-P and GPx-1 transcripts
      in ocular tissues were analyzed and the ciliary epithelium was found to express
      the highest levels of GPx-P transcripts in human and bovine eyes, whereas the
      cornea of calf eyes expressed the highest levels of GPx-1 transcripts.
      Surprisingly, the lens, on which oxidants have profound effects leading to
      cataract formation, expressed the lowest levels of GPx-P and GPx-1 transcripts in
      human donor eyes. These results provide new evidence of differential gene
      expression of the GPx-P and GPx-1 forms in the mammalian eye and stresses the
      functional role of the ocular ciliary epithelium in protecting the anterior
      segment of the eye from oxidative damage.

PMID- 8262912
TI  - Two mouse hypervariable minisatellites: chromosomal location and simultaneous
      mutation.
AB  - Pc-1 and Pc-2 hypervariable minisatellites of the mouse show a structural
      similarity and hence have been compared in terms of chromosomal location and
      mutability. Polymorphisms of the Pc-2 locus detected by analyses of Southern
      blotting and polymerase chain reaction were used for typing 61 backcross mice
      that were obtained by mating (C57BL/6 x MSM)F1 females to MSM males. Segregation
      patterns indicated that the Pc-2 locus maps to the 60 cM region of chromosome 6,
      while that of Pc-1 maps to chromosome 4. Simultaneous mutation of the two loci
      was examined in 101 F1 mice. Pc-1 and Pc-2 loci showed mutation rates of 14.4 and
      5.0% per gamete, respectively. Of the nine mice with a Pc-2 mutation, four
      carried a Pc-1 mutation at the same maternally- or paternally-derived allele. The
      rate of comutation was 44% (4/9), higher than the 12.2% (24/197) of Pc-1 mutation
      alone. This suggests that the germline mutation of the two hypervariable
      minisatellites may result from a common mechanism.

PMID- 8262913
TI  - Cloning of a new member of the peroxisome proliferator-activated receptor gene
      family from mouse liver.
AB  - Peroxisome proliferators are postulated to elicit predictable pleiotropic
      responses in the liver by activating a peroxisome proliferator-activated receptor
      (PPAR). PPARs from mouse liver (mPPAR), rat liver (rPPAR), and Xenopus liver
      (xPPAR gamma) have been cloned recently. We now report the cloning of a new
      member from mouse liver which we designate mPPAR gamma. mPPAR gamma cDNA
      contained an open reading frame encoding a 475-amino acid protein exhibiting 75%
      amino acid similarity to xPPAR gamma, while it showed only 55% identity with
      mPPAR. The ligand-binding and DNA-binding domains are best conserved between
      mPPAR gamma, mPPAR, and xPPAR gamma. Like rPPAR, mPPAR gamma is able to impart
      peroxisome proliferator responsiveness to the promoter of peroxisomal
      bifunctional gene, which encodes the second enzyme of the peroxisomal fatty acid
      beta-oxidation system. Northern blot analysis revealed high expression of mPPAR
      gamma gene in mouse liver, kidney, and heart and low expression in the lung,
      testis, brain, skeletal muscle, and spleen. In mice treated with ciprofibrate, a
      peroxisome proliferator, a 2-fold increase in mPPAR gamma mRNA was observed in
      the liver and kidney. The presence of two PPARs in the mouse liver suggests the
      possibility of multiple signaling pathways for the peroxisome proliferator
      induced pleiotropic responses.

PMID- 8262914
TI  - Primary structure of the heterosaccharide of the surface glycoprotein of
      Methanothermus fervidus.
AB  - The outer surface of the cells of the hyperthermophile Methanothermus fervidus is
      covered by crystalline glycoprotein subunits (S-layer). From the purified S-layer
      glycoprotein, a heterosaccharide was isolated. The heterosaccharide consists of D
      3-O-methylmannose, D-mannose, and D-N-acetylgalactosamine in a molar ratio of
      2:3:1 corresponding to a relative molecular mass of 1061.83 Da. 3-O-methylmannose
      could be partly replaced by 3-O-methylglucose. The primary structure of the
      glycan was revealed by methylation analysis, by plasma desorption mass
      spectrometry, and by high field NMR spectroscopy. The purified heterosaccharide
      is linked via N-acetylgalactosamine to an asparagine residue of the peptide
      moiety. The following structure is proposed for the heterosaccharide: alpha-D-3-O
      MetManp-(1-->6)-alpha-D-3-O-MetManp-((1-->2)-alp ha-D-Manp)3-(1-->4) - D-GalNAc.

PMID- 8262915
TI  - Directed evolution of biosynthetic pathways. Recruitment of cysteine thioethers
      for constructing the cell wall of Escherichia coli.
AB  - We report that expansion of thioether biosynthesis in Escherichia coli generates
      sulfur-containing amino acids that can replace meso-diaminopimelate, the
      essential amino acid used for cross-linking the cell wall. This was accomplished
      by jointly overexpressing the metB gene coding for L-cystathionine gamma-synthase
      and disrupting the metC gene, whose product, L-cystathionine beta-lyase, is
      responsible for the destruction of L-cystathionine and other L-cysteine
      thioethers. As a result, meso-lanthionine and L-allo-cystathionine were produced
      endogenously and incorporated in the peptidoglycan, thereby enabling E. coli
      strains auxotrophic for diaminopimelate to grow in its absence. Thus, current
      techniques of metabolic engineering can be applied to evolving the chemical
      constitution of living cells beyond its present state.

PMID- 8262916
TI  - The crystallographic structure of a human dihydropteridine reductase NADH binary
      complex expressed in Escherichia coli by a cDNA constructed from its rat
      homologue.
AB  - A human dihydropteridine reductase (EC 1.6.99.10) has been created from a rat
      cDNA clone by a single five-oligonucleotide mutagenesis reaction and expressed in
      good yield in Escherichia coli. The enzyme has been purified to homogeneity, and
      kinetic identity to the naturally occurring enzyme has been proven.
      Crystallization has also been achieved, and the crystal structure was solved
      using 2.5 A data that was refined to an R value of 16.9%. The structure described
      in this report represents the first complete structural characterization of this
      important human enzyme.

PMID- 8262917
TI  - Functional expression and properties of the tRNA(Lys)-specific core anticodon
      nuclease encoded by Escherichia coli prrC.
AB  - Escherichia coli carrying the optional locus prr harbor a latent, tRNA(Lys)
      specific anticodon nuclease, activated by the product of phage T4 stp. Anticodon
      nuclease latency is ascribed to the masking of prrC, implicated with the
      enzymatic activity, by flanking, type Ic DNA restriction modification genes
      (prrA, B&D-hsdM, S&R). Overexpression of plasmid-borne prrC elicited anticodon
      nuclease activity in uninfected E. coli. In vitro, the prr-C-coded core activity
      was indifferent to a synthetic Stp polypeptide, GTP, ATP, and endogenous DNA,
      effectors that synergistically activate the latent enzyme. Several facts
      suggested that PrrC is highly labile in the absence of the masking proteins. The
      core activity decayed with t1/2 below 1 min at 30 degrees C, and the PrrC portion
      of a fusion protein was unstable. Moreover, expression of prrC from its own
      promoter at low plasmid copy number did not allow detection of core activity.
      Yet, it sufficed for establishment of a latent, T4-inducible enzyme when
      complemented by the masking Hsd proteins, which were provided by another
      replicon. Interaction between the antagonistic components of latent anticodon
      nuclease was also demonstrated immunochemically. The coupling of anticodon
      nuclease with a DNA restriction modification system may serve to ward off its
      inadvertent toxicity and maintain it as an antiviral contingency.

PMID- 8262918
TI  - Membrane topology of the L-rhamnose-H+ transport protein (RhaT) from
      enterobacteria.
AB  - The L-rhamnose-H+ symporter (RhaT) is a 344-amino acid integral membrane protein,
      found in many Enterobacteria, which couples the uptake of the sugar L-rhamnose
      with the inward movement of protons. Based on its hydropathy profile and the
      application of von Heijne's "positive inside" rule (von Heijne, G. (1992) J. Mol.
      Biol. 225, 487-494), a model of the L-rhamnose-H+ symport protein (RhaT) is
      proposed containing 10 transmembrane helices with the NH2 and COOH termini in the
      periplasm. This model was tested by the creation of random beta-lactamase (Bla)
      fusions. The data from 33 unique, randomly generated, RhaT-Bla fusions and from 5
      site-specific fusions supported the proposed topology between transmembrane
      helices 2-10. However, the localization of the putative first hydrophilic loop
      and the NH2 terminus was not possible because the beta-lactamase fusions in this
      region were shown to be unreliable indicators of the topology of RhaT.

PMID- 8262919
TI  - Regulation of pathways of extramitochondrial fatty acid oxidation and liver fatty
      acid-binding protein by long-chain monocarboxylic fatty acids in hepatocytes.
      Effect of inhibition of carnitine palmitoyltransferase I.
AB  - The regulation of the extramitochondrial fatty acid oxidation pathways located in
      the peroxisomes and the endoplasmic reticulum is not fully understood. Although
      both long-chain dicarboxylic fatty acids, which are poorly metabolized in
      hepatocytes, and non-beta-oxidizable fatty acid analogs induce peroxisomal beta
      oxidation and liver fatty acid-binding protein (L-FABP) by a pretranslational
      mechanism, monocarboxylic long-chain fatty acids, which are rapidly esterified
      and oxidized, do not. To establish whether impaired utilization and, hence,
      sustained intracellular levels of monocarboxylic long-chain fatty acids increase
      their efficacy as inducers, the effect of oleic acid on cytochrome P-450 4A1,
      peroxisomal beta-oxidation, and L-FABP during inhibition of mitochondrial beta
      oxidation was determined. In primary hepatocyte cultures, oleic acid had no
      inducing effect, but in the presence of 2-tetradecylglycidic acid (TDGA), an
      inhibitor of carnitine palmitoyltransferase I, it induced P-450 4A1, peroxisomal
      beta-oxidation, and L-FABP pretranslationally. An increase in peroxisomal beta
      oxidation was also noted in the presence of etomoxir, another inhibitor of
      carnitine palmitoyltransferase I. Exposure of hepatocytes to TDGA for 1 h led to
      an expected decrease in incorporation of radiolabel from [1-14C]oleate into CO2
      and water-soluble products. In contrast, long-term exposure to TDGA increased
      incorporation of [1-14C]oleate into oxidation products, most likely due to an
      adaptive induction of peroxisomal beta-oxidation. Both acute and long-term
      exposure of hepatocytes to TDGA decreased incorporation of oleic acid into
      triglycerides, an effect that may have contributed to the intracellular
      accumulation of fatty acids. These results provide support for a mechanism by
      which long-chain fatty acids or specific metabolites, including long-chain acyl
      CoA esters and long-chain dicarboxylic acids, act as signals in the induction of
      P-450 4A1, peroxisomal beta-oxidation, and L-FABP under conditions in which long
      chain fatty acids accumulate due to impaired entry into the mitochondrial beta
      oxidation pathway.

PMID- 8262920
TI  - Limited proteolysis of triose-phosphate isomerase and characterization of the
      catalytically active peptide complex.
AB  - Limited proteolysis of the triose-phosphate isomerase (EC 5.3.1.1) by subtilisin
      generates peptides that remain noncovalently attached and catalytically active.
      Edman degradation of the peptides showed that the primary proteolytic sites for
      yeast triose-phosphate isomerase are the Leu174-Ala175 bond followed by Ser52
      Leu53. The Leu174-Ala175 site is of particular interest, since it forms part of
      the hinged lid that closes over the catalytic center, and this bond is only 12.2
      A (open) or 9.8 A (closed) from the catalytic residue Glu165. The higher Km,
      kcat, and kcat/Km values exhibited by the catalytically active peptide complex
      suggest that the substrate is not bound as tightly to the catalytic center. In
      addition, increased methylglyoxal formation by the cleaved enzyme indicates that
      the enzyme-substrate complex is less protected from the solvent. Circular
      dichroic and fluorescence spectra show that the overall structure of the peptide
      complex is similar to the native enzyme but with local structural perturbations
      around the tryptophans. Also, the peptide complex is more susceptible to
      denaturation by guanidine and exhibits lower Tm values, indicating a loose
      interaction between the fragments. Unfolding, dissociation, and refolding
      experiments suggest that the fragments have strong inherent secondary structural
      features and can reassociate into catalytically active structures.

PMID- 8262921
TI  - Kinetics of the uracil-DNA glycosylase/inhibitor protein association. Ung
      interaction with Ugi, nucleic acids, and uracil compounds.
AB  - The bacteriophage PBS2 uracil-DNA glycosylase inhibitor (Ugi) inactivates
      Escherichia coli uracil-DNA glycosylase (Ung) by forming an Ung.Ugi protein
      complex with 1:1 stoichiometry. Stability of the Ung.Ugi complex was demonstrated
      by the inability of free Ugi to exchange with Ugi bound in preformed complex. Ung
      was reacted with fluorescein 5-isothiocyanate to produce fluorescent-Ung (F-Ung),
      which retained full uracil-DNA glycosylase activity and susceptibility to Ugi
      inactivation. Addition of Ugi to F-Ung under steady-state conditions resulted in
      saturable (15%) fluorescence quenching at a F-Ung.Ugi ratio of 1:1.4.
      Dissociation constants determined for the F-Ung interaction with M13 DNA, uracil
      containing DNA, and poly(U) equaled 600, 220, and 190 microM, respectively. While
      F-Ung associated with nucleic acid polymers was able to bind Ugi efficiently, F
      Ung bound in the F-Ung.Ugi complex could no longer effectively bind nucleic acid.
      Stopped-flow kinetic analysis suggested the F-Ung/Ugi association was described
      by a two-step mechanism. The first step entailed a rapid pre-equilibrium
      distinguished by the dissociation constant Kd = 1.3 microM. The second step led
      irreversibly to the formation of the final complex and was characterized by the
      rate constant k = 195 s-1. We infer Ugi inactivates Ung through the formation of
      an exceptionally stable protein-protein complex.

PMID- 8262922
TI  - Membrane fusion-inhibiting peptides do not inhibit influenza virus fusion or the
      Ca(2+)-induced fusion of negatively charged vesicles.
AB  - Short hydrophobic N-carbobenzoxy oligopeptides are known to inhibit the
      infectivity of several enveloped viruses. Recently, it was shown that they
      inhibited the fusion of Sendai virus with N-methyl
      dioleoylphosphatidylethanolamine (N-methyl-DOPE) liposomes as well as the low pH
      induced fusion of these liposomes with each other (Kelsey, D.R., Flanagan, T. D.,
      Young, J. E., and Yeagle, P. L. (1990) J. Biol. Chem. 265, 12178-12183).
      Therefore it was concluded that the peptides inhibit membrane fusion, an
      important step in viral infectivity. Here, it is shown that this peptide and a
      series of similar peptides did not inhibit influenza virus fusion with N-methyl
      DOPE or other liposomes. In fact, some peptides enhanced the overall rate of
      fusion of influenza virus with N-methyl-DOPE liposomes. In our hands, the
      peptides did not inhibit influenza infectivity in Madin-Darby canine kidney cells
      or influenza-induced hemolysis either. They also did not inhibit the Ca(2+)
      induced fusion between cardiolipin or phosphatidylserine liposomes. However, the
      inhibitory effect of one of the peptides on the fusion of Sendai virus with N
      methyl-DOPE liposomes and on N-methyl-DOPE liposome-liposome fusion could be
      reproduced. These data indicate that the peptides do not, as had been suggested
      (Yeagle, P.L., Young, J.E., Hui, S.W., and Epand, R. M. (1992) Biochemistry 31,
      3177-3183), act by preventing the formation of lipid structures with small radii
      of curvature, such as the inverted phase intermediates that are thought to be
      involved in N-methyl-DOPE fusion. The results also suggest that the mechanism of
      inhibition of Sendai virus infection and N-methyl-DOPE fusion by the peptides may
      be different after all.

PMID- 8262923
TI  - Tyrosine 151 is part of the substrate activation binding site of bovine trypsin.
      Identification by covalent labeling with p-diazoniumbenzamidine and kinetic
      characterization of Tyr-151-(p-benzamidino)-azo-beta-trypsin.
AB  - Identification of the substrate activation site of beta-trypsin by a 1:1 reaction
      with p-diazoniumbenzamidine chloride was confirmed by spectral analysis.
      Proteolysis of Cm-p-benzamidino-azo-beta-trypsin provided peptides containing
      modified tyrosine residues. The major product, Ser-146 to Lys-156, which
      corresponded to labeling at Tyr-151, was recovered in 35% yield, and its
      structure was demonstrated by amino acid analysis, Edman degradation, and mass
      spectrometry. Yields of labeled Tyr-151, Tyr-39, and Tyr-172, identified by
      peptide analysis, were in the proportion of 100:7:3. Tyr-151-(p-benzamidino)-azo
      beta-trypsin is permanently activated, but can be further activated by
      substrates. Values of kcat, Ks', and kcat' vary from two to three times the
      equivalent values for trypsin. Berenil (4,4'-diazoamino-bis-benzamidine), a
      parabolic competitive inhibitor of beta-trypsin, was a hyperbolic competitive
      inhibitor of azo-beta-trypsin. Thus, Tyr-151, part of subsite S'2, affects the
      catalytic process and, when modified covalently, permanently activates trypsin.
      Equilibrium binding with berenil supported the kinetic data obtained with
      substrates. This permits the integration of protein modification, kinetics,
      equilibrium binding, and crystallographic data to demonstrate a fine interaction
      between subsites S1-S3 and S'2 in trypsin and azo-beta-trypsin, resulting in
      subtle structural changes when the native enzyme is covalently modified at Tyr
      151.

PMID- 8262924
TI  - Identification of oxygen responsive elements in the 5'-flanking region of the
      human glutathione peroxidase gene.
AB  - The -1389 to +588 region of the human genomic glutathione peroxidase gene (hgpx1)
      was amplified using the polymerase chain reaction. This DNA fragment was cloned
      and sequenced, and various deletion constructs derived from the hgpx1 5'-flanking
      region were fused to the chloramphenicol acetyltransferase gene. These reporter
      genes were analyzed in transient transfection assays using primary cultured human
      ventricular cardiomyocytes obtained from patients with tetralogy of Fallot. Two
      distinct regions upstream from the transcription start site, which was determined
      using S1 nuclease analysis, were identified to be responsive to the oxygen
      tension in culture (pO2 values of 150 or 40 mm Hg). Methylation interference
      footprinting assays revealed proteins closely apposed to two sequences located at
      -1232 to -1213 and -282 to -275. We have designated these oxygen responsive
      elements ORE1 and ORE2, respectively. Gel mobility shift assays using double
      stranded oligonucleotides corresponding to each site have demonstrated the
      formation of specific complexes using both cultured human cardiomyocyte and HeLa
      nuclear extracts. ORE1 and ORE2 bind disparate proteins with equal precision as
      bound complexes could be competed away with identical sequences but not with
      either the other ORE or an unrelated sequence. Insertion of these oxygen
      responsive elements into a reporter gene governed by a SV40 promoter similarly
      regulated chloramphenicol acetyltransferase activity according to the oxygen
      tension in culture.

PMID- 8262925
TI  - Inhibition of the calcium store-operated calcium entry pathway by chemotactic
      peptide and by phorbol ester develops gradually and independently along
      differentiation of HL60 cells.
AB  - N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibited transiently the entry of
      Ca2+ and Mn2+ induced by emptying with thapsigargin the Ca2+ stores of HL60 cells
      differentiated toward granulocytes. Phorbol 12,13-dibutyrate (PDB) produced a
      permanent inhibition of this store-operated Ca2+ entry pathway (SOCP), suggesting
      that inhibition was due to protein phosphorylation mediated by protein kinase C
      (PKC). Inhibition by PDB was prevented by the PKC inhibitors staurosporin and
      chelerythrine. Inhibition by fMLP was prevented by chelerythrine but only
      partially by staurosporin. The characteristics of the inhibition were similar to
      those reported in human neutrophils (Montero, M., Alvarez, J., and Garcia-Sancho,
      J. (1993) J. Biol. Chem. 268, 13055-13061). Neither fMLP nor PDB inhibited
      significantly SOCP in undifferentiated HL60 cells. Single-cell [Ca2+]i
      measurements at different stages of differentiation showed that inhibition by
      fMLP and PDB developed independently, suggesting different inhibitory mechanisms.
      The simplest explanation would be that inhibition by fMLP takes place through
      activation of a protein kinase distinct from PKC and that the PDB-activated PKC
      isoform necessary to phosphorylate and inhibit SOCP is expressed only along
      differentiation. Additionally, inhibition by both fMLP and PDB developed
      gradually. At intermediate stages of differentiation, PDB was able to produce a
      partial and maintained inhibition and fMLP a partial and short-lived inhibition
      of SOCP.

PMID- 8262926
TI  - The role of amino acids in ApoB100 synthesis and catabolism in human HepG2 cells.
AB  - The object of this study was to examine the effects of extracellular amino acids
      on hepatic apoB100 metabolism using a transformed human liver cell line (HepG2)
      as a hepatocyte model. The data demonstrate that reduced extracellular amino
      acids resulted in marked increases in apoB100 concentrations in the medium (87 +/
      10% increase; p < 0.002). These data contrast with the effects of amino acids on
      secretion of total hepatic protein into the medium, which increased by 541 +/-
      83% at 5.5 mg/ml amino acids compared to the low (0.5 mg/ml) amino acid medium (p
      < 0.01), pointing to a positive relationship between the concentration of amino
      acids in the medium and overall secretion of protein by the HepG2 cells. No
      significant effect of medium amino acid concentration on intracellular synthesis
      of cholesterol ester, cholesterol, triglyceride, or apoA1 secretion was evident.
      Amino acids also affected the activity of the low density lipoprotein pathway: at
      lower medium amino acid concentration, specific cell-associated radioactivity and
      cellular degradation were increased (117 +/- 24 and 233 +/- 13% at 0.5 versus 5.5
      mg/ml amino acids, respectively). Pulse-chase analysis demonstrated that there
      was no difference in secretion efficiency of apoB (36 +/- 6 versus 46 +/- 8% in
      low versus high amino acid medium, respectively), but that the initial amount of
      [3H]apoB synthesized was greater in the low amino acid medium (10.5 +/- 3.8
      versus 5.7 +/- 1.7 x 10(3) dpm [3H]apoB/mg of cell protein; p < 0.05). In
      contrast, the initial amount of [3H]albumin synthesized was much greater in the
      high amino acid medium (26.6 +/- 5.0 versus 54.6 +/- 19.0 x 10(3) dpm
      [3H]albumin/mg of cell protein in low versus high amino acid medium,
      respectively; p < 0.05). Slot blot analysis of apoB mRNA was 87 +/- 22% higher in
      lower amino acid medium as compared to the high amino acid medium (p < 0.01).
      These results demonstrate that amino acids have a profound negative regulatory
      effect on apoB synthesis and secretion and may shed light on the pathogenesis of
      some clinical dyslipidemias such as the increased plasma apoB levels in patients
      treated with continuous ambulatory peritoneal dialysis.

PMID- 8262927
TI  - Identification of the functional domains in heme O synthase. Site-directed
      mutagenesis studies on the cyoE gene of the cytochrome bo operon in Escherichia
      coli.
AB  - The cytochrome bo complex is a terminal ubiquinol oxidase in the aerobic
      respiratory chain of Escherichia coli and is encoded by the cyoABCDE operon.
      Recently, we have demonstrated that heme O at the high-spin heme-binding site is
      essential for redox-coupled proton pumping by the oxidase and suggested that the
      cyoE gene encodes a novel enzyme for heme O biosynthesis, protoheme IX
      farnesyltransferase (heme O synthase) (Saiki, K., Mogi, T., and Anraku, Y. (1992)
      Biochem. Biophys. Res. Commun. 189, 1491-1497). This study was focused to define
      the catalytic domain(s) of the CyoE protein via a site-directed mutagenesis
      approach. We have individually substituted 40 amino acid residues including 22
      invariant residues with alanines and found that 23 mutant oxidases were
      nonfunctional and exhibited a specific loss of the CO binding activity at the
      site of the high-spin heme. Characterizations of the purified D65A, Y120A, and
      W172A mutant oxidases, which represent the mutations of different topological
      domains, revealed that their defects are attributable to substitution of
      protoheme IX for heme O present in the high-spin heme-binding site. Based on the
      above observations, we suggest that the conserved amino acid residues present in
      the cytoplasmic loops II/III and IV/V are part of the catalytic center of heme O
      synthase.

PMID- 8262928
TI  - In vivo desaturation of cis-delta 9-monounsaturated to cis-delta 9,12
      diunsaturated alkenylether glycerolipids.
AB  - Plants convert lipid-bound cis-n-9 monoenoic to polyenoic fatty acid residues
      without involvement of corresponding CoA-thioesters. To provide additional
      evidence for this type of lipid-linked desaturation we incubated sn-1-O- and 2-O
      (cis-9)octadecenylglycerol isomers with photoautotrophic cell cultures from
      tomato. After 14 days the fractions of phosphatidylcholine and
      monogalactosyldiacylglycerol were isolated and the incorporated glycerol ether
      backbones released by treatment with LiAlH4 (reduction of ester bonds) and short
      acid hydrolysis (cleavage of enol ether bonds). High performance liquid
      chromatography and mass spectroscopy of the products in appropriately derivatized
      form showed that the (cis-9)octadecenyl group in the sn-1 position of the
      phospholipid was nearly completely desaturated to a (cis-9,12)octadecadienyl
      residue having the same double bond arrangement as linoleic acid. In the
      galactolipid fraction the desaturation had progressed to octadecatrienyl
      residues. Similarly, the octadecenyl residue in the sn-2 position of the
      phospholipid was nearly completely desaturated to an octadecadienyl group. These
      results are unambiguous proof for lipid-linked desaturation by both microsomal
      and plastidial desaturase systems of plants.

PMID- 8262929
TI  - Kinetics of factor Xa inhibition by tissue factor pathway inhibitor.
AB  - Tissue factor pathway inhibitor is a multivalent, Kunitz-type proteinase
      inhibitor. It directly inhibits factor Xa and, in a factor Xa-dependent fashion,
      produces feedback inhibition of the factor VIIa/tissue factor catalytic complex
      which is responsible for the initiation of coagulation. Human recombinant TFPI
      (rTFPI) produced in Escherichia coli was used to define the kinetic constants
      describing the human factor Xa:TFPI interaction. The inactivation of factor Xa by
      E. coli-rTFPI is indistinguishable from that of rTFPI produced in mammalian SK
      hepatoma cells, suggesting that post-translational modifications such as
      glycosylation and phosphorylation do not play a major role in the inhibitory
      process. The slow, tight-binding inhibition of factor Xa follows the scheme:
      [formula: see text] Where the enzyme (E) and inhibitor (I) form an initial,
      immediate collision complex (EI) that then isomerizes slowly to a tightened final
      EI* complex. In the absence of other additions, the initial Ki (=k2/k1) and final
      Ki* for the inhibition of factor Xa by E. coli-rTFPI are 1.24 nM and 26.4 pM,
      respectively. In the presence of calcium ions (5 mM) the interaction between
      factor Xa and rTFPI is substantially weaker, with a Ki of 42.7 nM and Ki* of 85.2
      pM. The addition of other components of the prothrombinase complex produces
      enhanced factor Xa inhibition predominantly through an effect on the initial Ki.
      In the presence of calcium ions and saturating concentrations of phospholipids
      and factor Va, the Ki and Ki* for factor Xa inactivation are 2.04 nM and 52.3 pM.
      The enhancing effect of heparin on the inhibitory process is concentration
      dependent and exhibits an optimum, reminiscent of the "template" model for
      heparin's acceleration of thrombin and factor IXa inhibition by antithrombin III.
      At optimal concentrations, the major mechanism of heparin action is also a
      reduction in the Ki of the initial encounter complex between factor Xa and rTFPI.

PMID- 8262930
TI  - The nature of the carbohydrate-peptide linkage region in glycoproteins from the
      cellulosomes of Clostridium thermocellum and Bacteroides cellulosolvens.
AB  - The cellulase complexes of two cellulolytic bacteria, Clostridium thermocellum
      and Bacteroides cellulosolvens, were subjected to extensive Pronase digestion.
      Glycopeptide fractions were isolated by gel permeation and fast protein liquid
      chromatography and analyzed by monosaccharide analysis, amino acid analysis,
      methylation analysis, and 1H NMR spectroscopy. Alkaline borohydride-induced
      deglycosylation/amino acid conversion and periodate oxidation studies on the
      glycopeptide fraction of the C. thermocellum cellulosome demonstrated that the
      earlier established collection of carbohydrate moieties with 3-O-Me-D-GlcpNAc
      alpha (1-->2)-[D-Galp-alpha (1-->3)]-D-Galf-alpha (1-->2)-D-Gal (where 3-O-Me-D
      GlcpNAc is 3-O-methyl-N-acetylglucopyranosamine, Galp is galactopyranose, and
      Galf is galactofuranose) as the major component, is O-linked to threonine via
      galactopyranose. Using the same approach for the glycopeptide fraction of the
      cellulase complex of B. cellulosolvens, it was found that the reported collection
      of carbohydrate moieties with D-Galf-alpha (1-->3)-D-GlcpNAc-alpha (1-->2)-D-Galf
      alpha (1-->2)-[D-Galf-beta (1-->3)]-D-Gal as the major component, is O-linked
      mainly to threonine and partly to serine via galactopyranose. In both species,
      the hydroxyamino-acid-bound galactopyranose residue has probably an alpha
      configuration. The carbohydrate chains appear as clusters located in highly
      Thr/Pro-rich peptide regions of the glycoproteins. The results are consistent
      with the notion that the glycosylation sites are localized in linker sequences
      which connect the various binding domains of the noncatalytic S1 subunit of the
      cellulosome.

PMID- 8262931
TI  - The hemoglobins of the bullfrog, Rana catesbeiana. The cDNA-derived amino acid
      sequences of the alpha chains of adult hemoglobins B and C: their roles in
      deoxygenation-induced aggregation.
AB  - The adult bullfrog (Rana catesbeiana) has two major tetrameric hemoglobins, B and
      C, which share a common beta chain but have different alpha chains. Components B
      and C associate upon deoxygenation to form a complex of the form BC2, a trimer of
      tetramers that depends on contacts between the alpha B and alpha C chains.
      Nucleotide sequences of cDNA transcripts for these chains have been determined.
      Transcripts were identified by analysis of the amino acid compositions of the
      tryptic peptides of the components and by partial amino acid sequencing. These
      results, together with the amino acid sequence of the beta chain (Tam, L.-T.,
      Gray, G. P., and Riggs, A. F. (1986) J. Biol. Chem. 261, 8290-8294), permit an
      analysis of the structures of the alpha 2 beta 2 tetramers of hemoglobins B and
      C. Molecular modeling suggests possible residues at the alpha B-alpha C
      interfaces in the BC2 trimer and additional alpha C-alpha C contacts that would
      form a closed ring of six alpha chain subunits that would further stabilize the
      BC2 trimer. Phylogenetic analysis of the alpha B sequence suggests that it may be
      a "tadpole" chain, the temporal expression of which has shifted from larva to
      adult.

PMID- 8262932
TI  - The hemoglobins of the bullfrog, Rana catesbeiana. Deoxygenation-linked
      association of tetrameric components B and C to form the trimer BC2:
      sedimentation analysis and oxygen equilibria.
AB  - Hemolysates from the adult bullfrog, Rana catesbeiana, show an unusually high
      degree of cooperativity of oxygen binding with Hill coefficients greater than 4.
      The principal components of the tetrameric hemoglobin, B and C, do not show this
      high cooperativity when isolated, but it reappears when the components are mixed.
      Sedimentation velocity measurements show that the unusual behavior results from
      the mixed association of components B and C to form complexes larger than
      tetramers. Computer simulation of the sedimentation behavior of mixtures of
      deoxygenated B and C components shows that the gradient profiles can be
      satisfactorily described in terms of an equilibrium between the B and C tetramers
      and a BC2 trimer. The simplest model consistent with the results is the mixed
      association: B + C<-->BC and BC + C<-->BC2, with the second binding constant
      being higher than the first, indicating significant cooperativity. The extent of
      association is highest at low pH and low temperature. The dissociation of the B.C
      complex with low oxygen affinity to higher affinity B and C molecules during
      oxygenation results in greatly increased cooperativity of oxygen binding with
      higher Hill coefficients than possessed by either component alone in equilibria
      measured between 5 and 25 degrees C and between pH 6 and 8.

PMID- 8262933
TI  - Epidermal growth factor stimulates a protein tyrosine kinase which is separable
      from the epidermal growth factor receptor.
AB  - The intrinsic protein tyrosine kinase activity of the epidermal growth factor
      (EGF) receptor is necessary for ligand-induced signaling. To determine whether
      cellular protein tyrosine kinases are substrates for EGF-activated receptors,
      phosphotyrosine-containing proteins were isolated from EGF-treated cells and
      assayed for tyrosine kinase activity using peptide substrates. A tyrosine kinase
      activity that is distinct from the EGF receptor was adsorbed to monoclonal anti
      phosphotyrosine antibody columns and eluted with phenyl phosphate. Near-maximal
      tyrosine phosphorylation of this kinase occurred within 1 min of cell stimulation
      with an ED50 for EGF of 2.5 nM. The kinase was deactivated by incubation with
      purified CD45 tyrosine phosphatase in vitro, but activity could be restored by
      incubation with purified EGF receptor and Mn2+ ATP. These results suggest a
      cascade of tyrosine kinase signaling analogous to well characterized
      serine/threonine kinase cascades.

PMID- 8262934
TI  - Effect of site-directed mutagenesis of conserved aspartate and arginine residues
      upon farnesyl diphosphate synthase activity.
AB  - All polyprenyl synthases catalyze the condensation of the allylic substrate,
      isopentenyl diphosphate, with a specific homoallylic diphosphate substrate.
      Polyprenyl synthases from Homo sapiens, Ratus rattus, Escherichia coli,
      Saccharomyces cerevisiae, Neurospora crassa, and Erwinia herbicola contain two
      conserved "aspartate-rich domains" (Ashby, M.N., and Edwards, P.A. (1992) J.
      Biol. Chem. 267, 4128-4136). In order to determine the importance of these
      domains in catalysis, the conserved aspartates or arginines in domains I and II
      of rat farnesyl diphosphate synthase were individually mutated to glutamate or
      lysine, respectively. The putative "active site" arginine (Brems, D.N., Breunger,
      E., and Rilling, H. C. (1981) Biochemistry 20, 3711-3718) was mutated to lysine.
      Each mutant enzyme was overexpressed in E. coli and purified to apparent
      homogeneity. Detailed kinetic analyses of the wild type and mutant enzymes
      indicated that mutagenesis of Asp104, Asp107, Arg112, Arg113, and Asp243 resulted
      in a decreased Vmax of approximately 1000-fold compared to wild type. However, no
      significant change in the Km values for either the isopentenyl diphosphate or
      geranyl diphosphate substrate were observed. The results strongly suggest that
      these amino acids, and to a lesser extent Asp244, are involved in either the
      condensation of isopentenyl diphosphate and geranyl diphosphate to form farnesyl
      diphosphate and/or the release of the farnesyl diphosphate product from farnesyl
      diphosphate synthase. The conservation of these amino acid residues in different
      enzymes from several species suggests that these domains play a similar role in
      other polyprenyl synthases.

PMID- 8262935
TI  - Regulatory elements that mediate expression of the gene for the angiotensin II
      type 1a receptor for the rat.
AB  - To analyze the mechanism of the cell type-specific expression of rat angiotensin
      II type 1a receptor (AT1a-R) gene, we isolated the 5'-portion of the gene and
      identified multiple positive and negative regulatory sequences that regulate its
      transcription. Primer extension and S1 mapping identified a transcriptional
      initiation site at 33 (position +1) base pairs (bp) downstream of TATA sequence.
      The transcriptional activities of various 5'-deletion mutants of the AT1a-R gene
      upstream region, fused to the chloramphenicol acetyltransferase (CAT) gene, were
      examined using rat vascular smooth muscle cells (A10) and glial cells expressing
      AT1a-R mRNA predominantly or PC12 cells expressing AT2-R and very small amounts
      of AT1a-R mRNA. A 980-bp 5'-flanking sequence contained at least three positive
      elements, P1 (-560 to -489), P2 (-331 to -201), and P3 (-201 to -61). P1 and P3
      were active in the tested three cells, and P2 was functional only in glial and
      PC12 cells. In addition to these positive elements, there was negative element,
      N1 (-489 to -331), which was active only in PC12 cells. These elements, when
      cotransfected with the AT1a-CAT fusion gene, had competitive effects against its
      promoter activity. The present study suggests the presence of multiple trans
      acting factors that act on these positive and negative cis-acting elements and
      regulate the cell type-specific expression of the rat AT1a-R gene.

PMID- 8262936
TI  - Biochemical and functional properties of recombinant human sickle hemoglobin
      expressed in yeast.
AB  - Previous studies had indicated that recombinant and natural human sickle
      hemoglobin had similar chemical properties (Martin de Llano, J. J., Schneewind,
      O., Stetler, G., and Manning, J. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 918
      922). In the present study, additional biochemical and physiological
      characterization of some primary through quaternary structural features of
      recombinant sickle hemoglobin are described. The molecular weight of the purified
      recombinant sickle hemoglobin was identical to natural sickle hemoglobin as
      determined by mass spectrometry, thus excluding extensive post-translational
      modification in the yeast system. Carboxypeptidases A and B together catalyzed
      the release of COOH-terminal amino acids at the same rate for recombinant and
      natural hemoglobin S, consistent with identity in their primary and secondary
      structures in this region of the molecule. The tryptic peptide maps of natural
      and recombinant hemoglobins were practically indistinguishable, indicating the
      same internal protein sequences for recombinant and natural hemoglobins. As a
      probe of the secondary structure of recombinant sickle Hb, the reactivity of the
      SH group of Cys-93(beta) was investigated for the glutathione sickle hemoglobin
      adduct, which has significant anti-gelling and anti-sickling properties. The
      position of glutathione at Cys-93(beta) was established by direct mass
      spectrometric analysis of enzyme digests; reduction of this derivative to the
      unmodified chains was also observed by mass spectrometry and by isoelectric
      focusing. The oxygen equilibrium curves of recombinant and natural sickle
      hemoglobin at high protein concentration were superimposable with identical Hill
      coefficients of 3.3. The response of recombinant sickle hemoglobin to chloride
      with respect to a lowered oxygen affinity was identical to that of natural sickle
      hemoglobin. The gelation properties of recombinant and natural sickle hemoglobins
      were identical at the high hemoglobin concentrations that occur in the red cell.
      Therefore, the yeast expression system synthesizes a completely functional
      recombinant sickle hemoglobin with the same biochemical and physiological
      properties as natural sickle hemoglobin with respect to features characteristic
      of its primary through quaternary structures.

PMID- 8262937
TI  - Kinetics of interaction between normal and proline 12 Ras and the GTPase
      activating proteins, p120-GAP and neurofibromin. The significance of the
      intrinsic GTPase rate in determining the transforming ability of ras.
AB  - Single turnover and equilibrium binding measurements on the interaction of Gly-12
      and Pro-12 Ras.GTP with the catalytic domains of the GTPase-activating proteins,
      p120-GAP and neurofibromin, have been made utilizing fluorescent 2'(3')O-(N
      methylanthraniloyl)-nucleotides. These have enabled the equilibrium dissociation
      constants (Kd) for their initial binding and the rate constants of the hydrolysis
      step to be measured. p120-GAP binds to both Ras proteins with a Kd of 17 microM,
      whereas neurofibromin binds to both Ras proteins with a Kd of 1 microM. Both p120
      GAP and neurofibromin increased the rate constant of the GTP hydrolysis step of
      Pro-12 Ras, but the maximal activation at 30 degrees C was 120-fold and 560-fold,
      as compared with 70,000- and 52,000-fold, with Gly-12 Ras. The affinity with
      which p120-GAP and neurofibromin binds to either Gly-12 or Pro-12 Ras protein was
      decreased dramatically by increasing ionic strength caused by addition of NaCl.
      The rate constant of the cleavage step of hydrolysis catalyzed by neurofibromin
      increases with increasing ionic strength, whereas that catalyzed by p120-GAP
      appears to be unaffected. The high ionic strength within the cell might result in
      a much lower overall GTPase-activating protein activity than is measured under
      conditions of low ionic strength in vitro, with p120-GAP being more severely
      inhibited. The GTP hydrolysis rate of Pro-12 Ras is 2-fold faster than that of
      normal Ras. The low oncogenicity of Pro-12 ras is explained by a model in which
      the intrinsic rates of hydrolysis and exchange, as well as GTPase-activating
      protein- and exchange factor-stimulated rates, are determinants of the biological
      activity of Ras proteins in fibroblasts.

PMID- 8262938
TI  - Biochemical analysis of Escherichia coli selenophosphate synthetase mutants.
      Lysine 20 is essential for catalytic activity and cysteine 17/19 for 8-azido-ATP
      derivatization.
AB  - A labile selenium donor compound, selenophosphate, is formed from selenide and
      ATP by selenophosphate synthetase. A cysteine residue (Cys-17) that is essential
      for catalytic activity of the enzyme (Kim, I.Y., Veres, Z., and Stadtman, T. C.
      (1992) J. Biol. Chem. 267, 19650-19654) is located in a glycine-rich segment near
      the N terminus of the protein. The possibility that this peptide sequence
      (HGAGCGCK) defines the ATP-binding site of the enzyme, as does a conserved ATP or
      GTP binding sequence (GXXXXGKS/T) found in several other proteins, was tested by
      site-specific mutagenesis. Thus His-13 and Gly-18 were changed to Asn and Val,
      respectively, and Lys-20 to Arg or Gln. Catalytic activity was markedly decreased
      by mutation of Lys-20 to Arg and abolished by mutation of Lys-20 to Gln. The
      mutation of Cys-19 and His-13 did not substantially alter the ATP Km and Vmax
      values, whereas the Gly-18 mutation resulted in a 4-fold increase in the ATP Km
      value compared with that of the wild type. ATP binding properties of the mutant
      enzymes were determined using Mn-[32P]ATP or Mn-[14C]ATP and gel filtration.
      Photoaffinity labeling of the proteins with [gamma-32P]8-azido-ATP showed that
      all mutant enzymes could be labeled with the ATP analog except those in which Cys
      17 or Cys-19 were replaced with serine.

PMID- 8262939
TI  - Stereospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from
      Forsythia intermedia.
AB  - Pinoresinol/lariciresinol reductase catalyzes the first known example of a highly
      unusual benzylic ether reduction in plants; its mechanism of hydride transfer is
      described. The enzyme was found in Forsythia intermedia and catalyzes the
      presumed regulatory branch-points in the pathway leading to
      benzylaryltetrahydrofuran, dibenzylbutane, dibenzylbutyrolactone, and
      aryltetrahydronaphthalene lignans. Using [7,7'-2H2]-pinoresinol and [7,7'
      2H3]lariciresinol as substrates, the hydride transfers of the highly unusual
      reductase were demonstrated to be completely stereospecific (> 99%). The incoming
      hydrides were found to take up the pro-R position at C-7' (and/or C-7) in
      lariciresinol and secoisolariciresinol, thereby eliminating the possibility of
      random hydride delivery to a planar quinone methide intermediate. As might be
      expected, the mode of hydride abstraction from NADPH was also stereospecific:
      using [4R-3H] and [4S-3H]NADPH, it was found that only the 4 pro-R hydrogen was
      abstracted for enzymatic hydride transfer.

PMID- 8262940
TI  - X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex
      with lactose at 2.9-A resolution.
AB  - S-Lac lectins are a family of soluble lactose-binding animal lectins, some of
      which have been implicated in modulating cell-cell and cell-matrix interactions
      through specific carbohydrate-mediated recognition. We report here the x-ray
      crystal structure of a representative member of this family, the human dimeric S
      Lac lectin, L-14-II, in complex with lactose, at 2.9-A resolution. The two-fold
      symmetric dimer is made up of two extended anti-parallel beta-sheets, which
      associate in a beta-sandwich motif. Remarkably, the L-14-II monomer shares not
      only the same topology, but a very similar beta-sheet structure with that of the
      leguminous plant lectins, suggesting a conserved structure-function relationship.
      Carbohydrate binding by L-14-II was found to involve protein residues that are
      very highly conserved among all S-Lac lectins. These residues map to a single DNA
      exon, suggesting a carbohydrate binding cassette common to all S-Lac lectins.

PMID- 8262941
TI  - Evidence for lysine 80 as general base catalyst of leucine dehydrogenase.
AB  - To elucidate the functional role of the lysyl residue highly conserved in
      NAD(P)(+)-dependent amino acid dehydrogenases, Lys-80 of leucine dehydrogenase
      from Bacillus stearothermophilus has been mutated into Ala, Arg, or Gln. All of
      the mutant enzymes had markedly reduced activities in the oxidative deamination,
      whereas the Michaelis constants for substrate and coenzyme did not change
      significantly upon the mutation, except for a 10-30-fold increase in Km values
      for alpha-keto-iso-caproate in the Ala and Gln mutants. The pH profiles of
      kinetic parameters of the mutants considerably differed from those of the wild
      type, in which two ionizable groups with pKa values of 8.9 and 10.7 must be
      unprotonated for catalysis and protonated for substrate binding, respectively.
      Combined with the analyses of solvent isotope effect and inhibition by substrate
      analogs, these results unequivocally show that the epsilon-amino group of Lys-80
      participates in catalysis as a general base, assisting the nucleophilic attack of
      a water molecule to the substrate alpha-carbon atom. Furthermore, the Ala mutant
      was markedly stimulated by primary amines depending on the pKa and molecular
      volume, suggesting that in the Ala mutant the added amines can partially replace
      the general base function of Lys-80 in the wild type enzyme.

PMID- 8262942
TI  - Asp96 deprotonation and transmembrane alpha-helical structural changes in
      bacteriorhodopsin.
AB  - The M-->N transition in the photocycle of bacteriorhodopsin involves the transfer
      of a proton from Asp96 to the retinylidene Schiff base, possibly through a
      network of hydrogen-bonded amino acid residues and water molecules (Rothschild,
      K. J., He, Y. W., Sonar, S., Marti, T., and Khorana, H. G. (1992) J. Biol. Chem.
      267, 1615-1622). A conformational change of the protein backbone is also observed
      during this transition. In this work, we have investigated the effects of
      replacing the residue Thr46, which might be part of this chain, with an aspartic
      acid. Both Fourier transform infrared and resonance Raman spectroscopy show that
      the chromophore structure of this mutant (T46D) is normal. However, N formation
      is accelerated and N decay is significantly slowed compared to wild-type
      bacteriorhodopsin. This effect causes the N intermediate to accumulate under
      steady-state illumination thereby facilitating spectroscopic studies under normal
      pH conditions. Fourier transform infrared difference spectroscopy reveals that
      like native bacteriorhodopsin, N formation in T46D involves deprotonation of
      Asp96, reprotonation of the Schiff base, and a change in the backbone secondary
      structure. However, in contrast to bacteriorhodopsin, bands assigned to the C = O
      stretch mode of the carboxylic acid group of Asp96 are upshifted by 10 cm-1
      reflecting a change in the Asp96 environment and a drop in its effective pKa
      throughout the photocycle. This change in the pKa can directly account for
      changes in the photocycle kinetics and indicates that Asp96
      deprotonation/protonation are the rate limiting steps in the formation and decay
      of the N intermediate. By studying the effects of H/D exchange, evidence is found
      that the backbone structural changes involve transmembrane alpha-helices. It is
      proposed that these structural changes serve to modulate the local environment
      and protonation state of Asp96 during the photocycle and are also essential for
      formation of the proton conducting hydrogen bonded network which functions during
      Schiff base reprotonation.

PMID- 8262943
TI  - nolMNO genes of Bradyrhizobium japonicum are co-transcribed with nodYABCSUIJ, and
      nolO is involved in the synthesis of the lipo-oligosaccharide nodulation signals.
AB  - A host-inducible lacZ fusion was mapped down-stream of the nodYABCSUIJ operon in
      Bradyrhizobium japonicum strain USDA110. Sequencing of this region identified
      three novel genes, nolMNO. RNA dot blot analysis showed that nolO transcription
      is nodD1-dependent and that a polar mutation in nodS, located 5 kilobases
      upstream of nolO, blocks the transcription of nolO. Coupled with the host
      inducible nature of nolO expression, these results indicate that nolMNO are part
      of a 9-kilobase operon, nodYABCSUIJnolMNO. The lipo-oligosaccharide nodulation
      signals produced by strains SL67 (nolO-) and SL65(nolNO-) were purified, and
      their chemical structures were determined. In addition to the wild-type signal
      molecules, both mutants produced modified compounds that are not produced by the
      parent strain USDA110. The most prevalent difference observed was the absence of
      the 2-O-methylfucosyl residue from the mutant structures. In addition,
      metabolites were found in which the N-acetylglucosamine residue at the reducing
      end was glycosidically linked to glycerol. These alterations in the profiles of
      nodulation signals produced by strains SL67 and SL65 were accompanied by reduced
      nodulation efficiency on all hosts tested.

PMID- 8262944
TI  - rBAT, related to L-cysteine transport, is localized to the microvilli of proximal
      straight tubules, and its expression is regulated in kidney by development.
AB  - We have recently isolated a renal cDNA clone (rBAT) that induces amino acid
      transport in oocytes either as a component or as a specific activator of a system
      bo,(+)-like transporter. (Bertran, J., Werner, A., Moore, M. L., Stange, G.,
      Markovich, D., Biber, J., Testar, X., Zorzano, A., Palacin, M., and Murer, H.
      (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 5601-5605. In order to obtain
      additional information on the rBAT protein, we have investigated the cellular
      localization of rBAT and its expression during development in rat kidney. A
      polyclonal antibody raised against rBAT recognizes a specific protein band of
      approximately 90 kDa, which is highly enriched in rat renal brush border
      membranes. Immunofluorescence and immunoelectron microscopy studies demonstrated
      that rBAT is expressed in the microvilli domain of S3 epithelial cells (i.e.
      straight tubules). The onset of rBAT mRNA expression in kidney was detected
      during late fetal life. In keeping with this, induction in oocytes of L-cystine
      uptake due to fetal rBAT-related mRNA was approximately 10% of the induction
      obtained with rBAT-related mRNA from adult kidneys. rBAT mRNA levels were low in
      early postnatal life, and only at the end of lactation did they increase steeply,
      attaining approximately 50% of adult values after weaning. rBAT protein was
      undetectable in total membrane preparations of kidneys from fetuses and early
      neonates, weakly detected during lactation, and represented < 15% of adult values
      after weaning. The postnatal expression of rBAT and its specific location in the
      microvilli of epithelial cells from the S3 segment of the proximal tubule
      coincide with postnatal maturation of cystine resorption and with the site of
      high affinity resorption of cysteine in kidney. This is consistent with the
      involvement of rBAT in a b(o,+)-like high-affinity resorption system for cysteine
      in the proximal straight tubule of the nephron.

PMID- 8262945
TI  - Quantal Ca2+ release from caffeine-sensitive stores in adrenal chromaffin cells.
AB  - In populations of fura-2-loaded chromaffin cells, caffeine caused a concentration
      dependent increase in the intracellular Ca2+ concentration ([Ca2+]i), in the
      presence or absence of external Ca2+ ([Ca2+]o), that was saturable, reversible,
      and inhibited in a use-dependent fashion by ryanodine. These data confirm that
      caffeine mobilizes Ca2+ from the ryanodine-sensitive intracellular stores in
      chromaffin cells. In nominally Ca(2+)-free medium, sustained stimulation of cell
      populations or single cells with low caffeine concentrations failed to completely
      empty the caffeine-sensitive stores. In each case, there was a transient [Ca2+]i
      elevation, but a subsequent challenge with a higher caffeine concentration evoked
      a further [Ca2+]i rise, indicating that Ca2+ stores within individual cells were
      heterogeneous in their sensitivities to caffeine and that caffeine-induced Ca2+
      release was quantal. The heterogeneous sensitivity was also demonstrated using
      ryanodine; pretreatment of cell populations with increasing caffeine
      concentrations with a constant ryanodine concentration, caused a dose-dependent
      irreversible inhibition of the response to the subsequent addition of a maximal
      caffeine concentration. We conclude that, within single chromaffin cells,
      intracellular Ca2+ stores are heterogeneous in their sensitivity to caffeine and
      the fraction of Ca2+ stores mobilized by caffeine increases in direct proportion
      to the caffeine concentration.

PMID- 8262946
TI  - Differential processing of proenkephalin by prohormone convertases 1(3) and 2 and
      furin.
AB  - Recombinant vaccinia virus vectors were used to coexpress mouse prohormone
      convertase 1 (mPC1), mPC2, or human furin together with human proenkephalin in
      GH4C1 cells (rat pituitary somatomammotrophs) to examine the proteolytic
      processing of proenkephalin by these enzymes. Radioimmunoassays performed on high
      pressure gel permeation size-fractionated extracts obtained from GH4C1 cells and
      corresponding conditioned media revealed distinct profiles of immunoreactivity
      for products generated by each enzyme. PC1 produced intermediate sized processing
      products (3-10 kDa); the major immunoreactive enkephalin-containing species
      observed eluted at the positions of peptide B, the 5.3-kDa fragment, and free
      Leu5-enkephalin. PC2 exhibited a more complete processing profile. The major
      immunoreactive enkephalins produced were free Met5-enkephalin-Arg-Phe, free Met5
      enkephalin-Arg-Gly-Leu, free Leu5-enkephalin, and free Met5-enkephalin. Thus PC2
      appears to be more capable of generating active opioid units from proenkephalin
      than is PC1. Finally, furin cleaved proenkephalin to generate peptide B, an
      unidentified peak between the 18- and 5.3-kDa fragments, and a small amount of
      the 5.3-kDa fragment. Radiosequencing data verified that the production of the
      5.3-kDa fragment by PC1 occurred as a result of a Lys-Lys cleavage. The ability
      of PC1 to cleave proenkephalin (but not proopiomelanocortin) at a Lys-Lys site
      implies that the structural context of the paired basic cleavage site may be more
      important in the determination of cleavage specificity than the particular pair
      of basic residues at the site.

PMID- 8262947
TI  - The mannose transporter of Escherichia coli. Structure and function of the
      IIABMan subunit.
AB  - The mannose transporter of the bacterial phosphotransferase system consists of
      two transmembrane subunits (IICMan and IIDMan) and a hydrophilic subunit
      (IIABMan). IIABMan has two flexibly linked domains containing one phosphorylation
      site each and occurs as a dimer. Substrate transport is coupled to
      phosphorylation. The phosphoryl group is transferred from a phosphoryl carrier
      protein to His10 on IIA, hence to His175 on IIB and finally to the substrate.
      IIABMan mutants were analyzed in vitro for complementation, negative dominance,
      cysteine cross-linking and reactivity. CONCLUSIONS: (i) His10, Trp12, Lys48, and
      Ser72 form a functional unit (phosphorylation site 1); (ii) His86 on the IIA
      domain and His175 on the IIB domain of the same subunit form a functional unit
      (phosphorylation site 2); (iii) phosphoryl transfer can occur between His10 and
      His175 of the same as well as of different subunits and His86 is necessary for
      this transfer; (iv) the subunits in the dimer are interdependent; (v) The
      phosphorylation site mutant H175C is highly reactive toward thiol reagents and it
      forms extensive homo- and heterocross-links with other surface-exposed cysteines.
      The phosphorylation site mutant H10C is 1000-fold less reactive. The two residues
      might be in complementary locations, His10 buried in a concave, His175 exposed on
      a convex surface.

PMID- 8262948
TI  - Genetic and biochemical studies of bacteriophage T4 DNA polymerase 3'-->5'
      exonuclease activity.
AB  - DNA polymerase exonucleolytic proofreading is important in attaining high
      fidelity DNA replication. One of the most well characterized proofreading
      activities is the 3'-->5'-exonuclease activity of bacteriophage T4 DNA
      polymerase. We have used genetic analyses and protein sequence comparisons to
      Escherichia coli DNA polymerase I to identify amino acids in the N-terminal
      region of T4 DNA polymerase that are required for exonucleolytic proofreading.
      Mutant DNA polymerases with amino acid substitutions D112A/E114A, D219A, or D324A
      reduced 3'-->5'-exonuclease activity 10(2)-10(4)-fold in various in vitro assays
      and decreased DNA replication fidelity in vivo. DNA replication activity was also
      reduced for the exonuclease-deficient DNA polymerases in vitro and in vivo.
      Reduction in DNA replication appeared to be due primarily to the interdependence
      of T4 DNA polymerase replication and proofreading activities; T4 DNA polymerase
      requires 3'-->5'-exonuclease activity to repair primer termini that are not
      suitable substrates for extension. Observations reported here provide further
      evidence in support of the proposal that DNA polymerases have distinct 3'-->5'
      exonuclease and polymerase active sites.

PMID- 8262949
TI  - Characteristics and significance of DNA binding activity of plasmid stabilization
      protein ParD from the broad host-range plasmid RK2.
AB  - A region of the plasmid RK2 has been shown to stabilize plasmid replicons in a
      broad host-range manner. This region encodes two divergently transcribed operons:
      parCBA and parDE. The parCBA operon specifies a multimer resolution system, while
      the parDE operon alone is capable of stabilizing an RK2-derived minireplicon
      under defined growth conditions in several different Gram-negative bacteria. The
      observed autoregulation of the parDE operon is most likely the result of ParD
      protein binding within the PparDE region. The characteristics of ParD binding to
      this region and the role of such binding in plasmid stabilization were examined
      with purified ParD protein. The results indicate that the binding of a single
      dimer of ParD protein to the promoter region most likely blocks interaction of
      RNA polymerase holoenzyme with the promoter. DNase I protection experiments
      indicate that ParD binds to a discrete sequence of 48 base pairs in length. While
      the binding of ParD to PparDE is essential for proper regulation of expression of
      the ParD and ParE proteins in vivo, the analyses of binding properties of mutant
      ParD proteins suggest that binding to this region does not play a direct role in
      plasmid stabilization.

PMID- 8262950
TI  - Purification and characterization of UDP-GlcNAc:Gal beta 1-4Glc(NAc) beta-1,3-N
      acetylglucosaminyltransferase (poly-N-acetyllactosamine extension enzyme) from
      calf serum.
AB  - UDP-GlcNAc:Gal beta 1-4Glc(NAc) beta-1,3-N-acetylglucosaminyltransferase is
      involved in the initiation and the extension of poly-N-acetyllactosamine
      biosynthesis. This enzyme has been purified to about 125,000-fold with a 0.2%
      yield from calf serum. The purification was achieved by ammonium sulfate
      precipitation and chromatography on concanavalin A-Sepharose, DEAE-Toyopearl, SP
      Toyopearl, Sephacryl S-200, AF-Blue-Toyopearl, and Mono Q columns. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis showed a single band corresponding to
      an apparent M(r) of 70,000. This component was specifically photoaffinity-labeled
      with 4-thiouridine diphosphate. Exoglycosidase digestion and methylation analysis
      of the reaction products demonstrated that the enzyme catalyzed the transfer of
      one N-acetylglucosamine to position C-3 of the terminal galactosyl residue of
      lactose or N-acetyllactosamine in the beta linkage. The enzyme required Mn2+ ions
      for its activity and showed a broad pH optimum around 7.0. Apparent Km values for
      lactose, N-acetyllactosamine, and UDP-GlcNAc were 18.2, 19.6, and 0.129 mM,
      respectively. Acceptor specificity was tested using several oligosaccharides. The
      results indicated that terminal Gal beta 1-4Glc(NAc) sequences (type II chains)
      were preferred substrates for the enzyme. Terminal Gal beta 1-3GlcNAc sequences
      (type I chains), Lewis X trisaccharides (Gal beta 1-4(Fuc alpha 1-3)GlcNAc), and
      monosaccharides (galactose) did not serve as substrates.

PMID- 8262951
TI  - Retinol bound to cellular retinol-binding protein is a substrate for cytosolic
      retinoic acid synthesis.
AB  - Retinol bound to cellular retinol-binding protein (CRBP) was found to be oxidized
      to retinoic acid by a soluble activity from calf liver. Cytosolic retinoic acid
      synthesis from retinol-CRBP was strictly dependent on the exogenous supply of
      either NAD or NADP. NAD-supported reactions carried out in the presence or in the
      absence of dimethyl sulfoxide yielded apparent Km and Vmax values for the retinol
      CRBP complex of 3.5 +/- 0.6 microM, 611 +/- 49 pmol h-1 (mg of protein)-1, and
      0.84 +/- 0.12 microM, 601 +/- 38 pmol h-1 (mg of protein)-1, respectively. The
      corresponding values for the oxidation of free retinol, dissolved in dimethyl
      sulfoxide, were 7.1 +/- 0.3 microM and 948 +/- 47 pmol h-1 (mg of protein)-1.
      Since the dissociation constant of the bovine retinol-CRBP complex is less than
      10(-8) M, whereas the Km for retinol-CRBP is of the same order as the Km for free
      retinol, synthesis of retinoic acid from retinol-CRBP does not rely on prior
      dissociation of retinol. ApoCRBP proved to be a specific inhibitor of retinoic
      acid synthesis from CRBP-bound retinol. Its inhibitory effect was
      indistinguishable from the dilution of the radioactive retinol-CRBP substrate
      that was obtained by the addition of unlabeled holoCRBP. In contrast, the
      oxidation of CRBP-bound retinol was not inhibited by the addition of other
      retinoid binding proteins nor by the addition of either free retinol or retinol
      complexed with proteins distinct from CRBP. These results indicate that the
      protein moiety of holoCRBP is specifically recognized by the cytosolic enzyme
      system that catalyzes retinoic acid synthesis from CRBP-bound retinol.

PMID- 8262952
TI  - Fibronectin inhibits platelet aggregation independently of RGD sequence.
AB  - Fibronectin binds to platelet membrane glycoprotein (GP) IIb-IIIa in Arg-Gly-Asp
      (RGD)-dependent and -independent manner. We have isolated and characterized the
      29-kDa dispase fragment of fibronectin. Binding of 125I-fibronectin to thrombin
      stimulated platelets was inhibited by the 29-kDa fragment and the GRGDSPA peptide
      with IC50 values of 1.5 +/- 0.4 and 8.1 +/- 0.9 microM, respectively. The NH2
      terminal sequence of this fragment gave this result: Ala-Val-Thr-Thr-Ile-Pro-Ala
      Pro-Thr-Asp. This established the position of this peptide within fibronectin as
      beginning with the residue tentatively designated 1597. Neither the RGDS sequence
      nor the RGD-independent binding domain of fibronectin (Bowditch, R. D., Halloran,
      C. E., Aota, S., Obara, M., Plow, E. F., Yamada, K. M., and Ginsberg, M. H.
      (1991) J. Biol. Chem. 266, 23323-23328) was contained in this fragment. The 29
      kDa fragment inhibited ADP-induced aggregation of platelets and binding of
      fibrinogen to activated platelets. The fragment bound to immobilized GPIIb-IIIa.
      The 125I-labeled 29-kDa fragment directly bound to thrombin-stimulated platelets
      with 98,000 +/- 4,600 molecules/platelet (Kd = 4.6 +/- 0.5 x 10(-6) M). Direct
      binding was inhibited by the unlabeled 29-kDa fragment but was not blocked by
      either the GRGDSPA peptide or the monoclonal anti-GPIIb-IIIa antibody. These
      results indicate that the additional RGD-independent binding domain(s) to GPIIb
      IIIa are present on fibronectin. This additional binding domain(s) on fibronectin
      may prevent thrombus formation by interfering with the interaction of fibrinogen
      with GPIIb-IIIa.

PMID- 8262953
TI  - Purification and characterization of a new DNA polymerase from budding yeast
      Saccharomyces cerevisiae. A probable homolog of mammalian DNA polymerase beta.
AB  - A new DNA polymerase activity was identified and purified to near homogeneity
      from extracts of mitotic and meiotic cells of the yeast Saccharomyces cerevisiae.
      This activity increased at least 5-fold during meiosis, and it was shown to be
      associated with a 68-kDa polypeptide as determined by SDS-polyacrylamide gel
      electrophoresis. This new DNA polymerase did not have any detectable 3'-->5'
      exonuclease activity and preferred small gapped DNA as a template-primer. The
      activity was inhibited by dideoxyribonucleoside 5'-triphosphates and N
      ethylmaleimide but not by concentrations of aphidicolin which completely inhibit
      either DNA polymerases I (alpha), II (epsilon), or III (delta). Since no
      polypeptide(s) in the extensively purified DNA polymerase fractions cross-reacted
      with antibodies raised against yeast DNA polymerases I, II, and III, we called
      this enzyme DNA polymerase IV. The DNA polymerase IV activity increased at least
      10-fold in a yeast strain overexpressing the gene product predicted from the
      YCR14C open-reading frame (identified on S. cerevisiae chromosome III and
      provisionally called POLX), while no activity was detected in a strain where POLX
      was deleted. These results strongly suggest that DNA polymerase IV is encoded by
      the POLX gene and is a probable homolog of mammalian DNA polymerase beta.

PMID- 8262954
TI  - Synthesis of glucosinolate precursors and investigations into the biosynthesis of
      phenylalkyl- and methylthioalkylglucosinolates.
AB  - The alkenyl and aromatic glucosinolates in oilseed rape (Brassica napus) are
      biosynthesized from chain-extended homologues of protein amino acids, including
      methionine and phenylalanine. Homologues of these two amino acids,
      homophenylalanine (2-amino-4-phenylbutyric acid) and dihomomethionine (2-amino-6
      methylthiohexanoic acid) were synthesized both with and without a 1-14C label.
      Microsomal preparations from oilseed rape leaves were shown to contain enzyme
      systems which metabolize these compounds, with loss of 14CO2, and produce the
      aldoxime intermediates possible in the biosynthetic pathway utilizing
      homophenylalanine. These were characterized by comparison with authenticated
      synthetic compounds. Potential intermediates on the pathway between
      homophenylalanine and its corresponding aldoxime, the N-hydroxyamino- and the
      oximino acids, were synthesized and their possible role in the pathway
      investigated.

PMID- 8262955
TI  - Two functionally different domains of rabphilin-3A, Rab3A p25/smg p25A-binding
      and phospholipid- and Ca(2+)-binding domains.
AB  - Rabphilin-3A is a putative target molecule for rab3A p25/smg p25A, which is a
      member of a ras p21-related small GTP-binding protein and implicated in
      neurotransmitter release from the synapse. Rabphilin-3A has two copies of an
      internal repeat that are homologous to the C2 domains of protein kinase C,
      synaptotagmin, and phospholipase A2, which are known to bind to phospholipid in a
      Ca(2+)-dependent manner. In the current study, we have investigated the
      functional domains or rabphilin-3A by use of three recombinant proteins as
      follows: full rabphilin-3A (1-704 amino acids), an N-terminal fragment (1-280
      amino acids), and a C-terminal fragment containing the C2 domains (281-704 amino
      acids). Both rabphilin-3A and the C-terminal fragment bound to phospholipid in
      the presence of Ca2+, but the N-terminal fragment did not bind to phospholipid.
      45Ca2+ bound to rabphilin-3A and the C-terminal fragment only in the presence of
      phospholipid but did not bind to the N-terminal fragment. The GTP gamma S-bound
      form of rab3A p25 bound to both rabphilin-3A and the N-terminal fragment but did
      not bind to the C-terminal fragment. These results indicate that rabphilin-3A has
      at least two functionally different domains, the N-terminal rab3A p25-binding and
      C-terminal phospholipid- and Ca(2+)-binding domains.

PMID- 8262956
TI  - Intracomplex electron transfer between ruthenium-cytochrome c derivatives and
      cytochrome c1.
AB  - The reactions of a beef heart cytochrome c1 preparation containing the hinge
      protein with horse cytochrome c derivatives labeled at specific lysine amino
      groups with (dicarboxybipyridine)(bisbipyridine)ruthenium(II) (Ru(II)) were
      studied by flash photolysis. All of the ruthenium-cytochrome c derivatives formed
      complexes with cytochrome c1 in low ionic strength buffer (5 mM sodium phosphate,
      pH 7). Excitation of Ru(II) to Ru(II*) with a 0.4-microseconds laser flash
      resulted in rapid electron transfer to the ferric heme group in cytochrome c,
      followed by electron transfer from the ferrous heme group of cytochrome c to the
      ferric heme group of cytochrome c1. The kinetic difference spectra displayed
      maxima at 546 nm and minima at 554 nm characteristic of electron transfer between
      the two cytochromes. The rate constants were independent of concentration at low
      ionic strength, indicating intracomplex electron transfer. The rate constants
      were 4,800, 6,800, 22,000, and 22,000 s-1 for cytochrome c derivatives modified
      at lysines 13, 27, 25, and 72, respectively. The observed rate constants were
      independent of ionic strength up to about 50 nM and then decreased progressively
      with further increases in ionic strength indicating dissociation of the complex.
      Second-order kinetics were observed at 310 mM ionic strength, with rate constants
      of 1.0 x 10(6), 1.6 x 10(7), 1.2 x 10(8), and 3.0 x 10(7) M-1 s-1 for the
      derivatives modified at lysines 13, 27, 25, and 72, respectively. The ionic
      strength dependence of the second-order rate constants is comparable to that
      involving native horse cytochrome c and is consistent with electron transfer
      reactions between oppositely charged proteins.

PMID- 8262957
TI  - Mapping of the pressure response element of the c-fos gene by direct DNA
      injection into beating hearts.
AB  - In vivo gene transfer into various organs of postnatal animals has recently been
      demonstrated. We applied this technique in order to map the promoter element of
      the protooncogene c-fos in the myocardium that responds to left ventricular
      pressure overload in vivo. Beating rat hearts were directly injected with a
      recombinant plasmid containing a 356-base pair upstream regulatory element of the
      mouse c-fos gene fused to a reporter gene. Two days after the injection, the
      hearts were excised and buffer-perfused. Acute pressure overload was applied for
      2 h by inflating an intraventricular balloon. Pressure overload increased the
      myocardial reporter gene activity by 3-8-fold (p < 0.01). Deletion and point
      mutations in the serum response element (SRE) of the c-fos promoter resulted in
      loss of pressure-induced reporter gene expression, indicating that the SRE is
      necessary for pressure response. The SRE alone was sufficient to confer pressure
      responsiveness to the minimal c-fos promoter, confirming that the pressure
      response element coincides with the SRE. A construct containing a point mutation
      at the p62TCF binding site of the SRE did not respond to pressure overload or to
      a protein kinase C activator but retained responsiveness to a calcium ionophore.
      This suggests that pressure overload may activate the c-fos promoter by a protein
      kinase C-dependent pathway. Thus, a directly injected gene can be regulated in
      the host cells by a physical stimulus to the intact organ. The in vivo DNA
      injection technique is a useful method to study complex organ physiology at the
      molecular level.

PMID- 8262958
TI  - Nitric oxide and nitric oxide-generating agents induce a reversible inactivation
      of protein kinase C activity and phorbol ester binding.
AB  - Since S-nitrosylation of protein thiols is one of the cellular regulatory
      mechanisms induced by nitric oxide (NO), and since protein kinase C (PKC) has
      critical thiol residues which influence its kinase activity, we have determined
      whether NO could regulate this enzyme. Initial studies were carried out with
      purified PKC and the NO-generating agent S-nitrosocysteine. This agent decreased
      phosphotransferase activity of PKC in a Ca(2+)- and oxygen-dependent manner with
      an IC50 of 75 microM. Phorbol ester binding was affected partially only at higher
      concentrations (> 100 microM) of S-nitrosocysteine. This inactivation of PKC was
      blocked by the NO scavenger oxyhemoglobin or reversed by dithiothreitol. It is
      likely that NO initially induced an S-nitrosylation of vicinal thiols, which were
      then oxidized to form an intramolecular disulfide. Other NO-generating agents
      such as S-nitroso-N-acetylpenicillamine and sodium nitroprusside, as well as
      authentic NO gas, induced similar types of PKC modifications. In intact B16
      melanoma cells treated with S-nitrosocysteine a rapid decrease in PKC activity in
      both cytosol and membrane was observed. Unlike in experiments with purified PKC,
      in intact cells treated with S-nitrosocysteine the phorbol ester binding also
      decreased to a rate equal to that of PKC activity. These modifications were
      readily reversed by treating the homogenates with dithiothreitol in test tubes or
      by removing the NO-generating source from intact cells. To determine whether the
      limited amounts of NO generated within the intact cells could induce this type of
      PKC modification, the macrophage cell line IC-21 was treated with
      lipopolysacharide and Ca2+ ionophore A23187 to induce the NO production. With an
      increase in generation of NO (3-12-h period) in these cells, a parallel and
      irreversible decrease in PKC activity and phorbol ester binding was observed. A
      specific inhibitor for NO synthase, NG-monomethyl-L-arginine, inhibited both the
      production of NO and PKC inactivation. In experiments using purified enzyme or
      intact cells there was no decrease in cAMP-dependent protein kinase activity.
      Conceivably, NO production for limited time induces a reversible inactivation of
      PKC due to the formation of a disulfide bridge(s), whereas the chronic production
      of NO could induce irreversible inactivation of PKC. The reversible or
      irreversible inactivations of PKC may in part influence NO-mediated
      cytoprotective or cytotoxic actions, respectively.

PMID- 8262959
TI  - Regulation of asialoglycoprotein receptor activity by a novel
      inactivation/reactivation cycle. Receptor reactivation in permeable rat
      hepatocytes is mediated by fatty acyl coenzyme A.
AB  - We previously reported that a subpopulation of asialoglycoprotein receptors (ASGP
      Rs), designated State 2 ASGP-Rs, can be inactivated in digitonin-permeabilized
      hepatocytes in the absence of cytosol by a process that is temperature- and ATP
      dependent (Medh, J. D., and Weigel, P. H. (1991) J. Biol. Chem. 266, 8771-8778).
      Here we show that these inactivated ASGP-Rs are reactivated by the sole addition
      of fatty acyl-CoA. Of the derivatives tested (acyl chain length 4-18), palmitoyl
      CoA was the most effective, although stearoyl-CoA (C18) and myristoyl-CoA (C14)
      were also active. Lauroyl-CoA (C12) was about half as effective as palmitoyl-CoA,
      and decanoyl-CoA (C10) and butyl-CoA (C4) were inactive. ASGP-R reactivation did
      not take place in the presence of free palmitate and coenzyme A, but did occur if
      low levels of ATP were also added to drive palmitoyl-CoA synthesis by the
      permeable cells. Addition of ATP after ASGP-R reactivation with palmitoyl-CoA
      again resulted in a rapid inactivation of these receptors. The extent and rate of
      this second ASGP-R inactivation process were proportional to ATP concentration;
      half-maximal effects occurred at approximately 0.5 mM ATP. ATP also rapidly
      reversed the ASGP-R reactivation seen with the other fatty acyl-CoAs. The results
      demonstrate the existence of a previously unrecognized pathway that regulates the
      activity of the ASGP-R population responsible for the majority of ligand
      endocytosis and processing in hepatocytes. This novel receptor
      inactivation/reaction cycle could ensure the high efficiency of segregating
      ligand and receptor during endocytosis and receptor recycling.

PMID- 8262960
TI  - Multiple mRNAs from the Punch locus of Drosophila melanogaster encode isoforms of
      GTP cyclohydrolase I with distinct N-terminal domains.
AB  - The GTP cyclohydrolase I gene of Drosophila melanogaster, the Punch locus,
      encodes alternative transcripts of 1.7 and 1.75 kilobases (kb). These transcripts
      are differentially expressed throughout Drosophila development. cDNA clones
      representing these transcripts, corresponding genomic regions and polymerase
      chain reaction-amplified primer extensions of the 5' ends of the RNAs were
      sequenced. Both RNAs contain five exons and derive from primary transcripts that
      extend over approximately 8 and 4 kb for the 1.7- and 1.75-kb RNAs, respectively.
      Their 5'-most exons are unique and spliced onto common 3' exons. The cDNAs each
      contain a single long open reading frame, which can be translated into a
      polypeptide of 273 amino acids for the 1.7-kb mRNA and 308 amino acids for the
      1.75-kb mRNA. The unique exons confer distinct N-terminal domains to each
      predicted protein. Sequence comparisons reveal that the Drosophila GTP
      cyclohydrolase isoforms encoded by the multiple transcripts are highly similar to
      GTP cyclohydrolases from humans, rodents, and bacteria, with one significant
      exception. The N-terminal domains encoded by the transcript-specific 5' exons
      cannot be aligned with the N termini of any other GTP cyclohydrolases. These
      domains are predicted to confer distinct physical characteristics to the
      alternate isoforms, and it is hypothesized that they aid in regulating the
      expression of the enzyme in diverse cellular environments.

PMID- 8262961
TI  - The nucleotide binding site of the helicase/primase of bacteriophage T7.
      Interaction of mutant and wild-type proteins.
AB  - The helicase and primase activities of bacteriophage T7 are distributed between
      the 56- and 63-kDa gene 4 proteins. The 63-kDa protein catalyzes both helicase
      and primase activities. The 56-kDa gene 4 protein lacks the 63 amino acids at the
      N terminus of the colinear 63-kDa protein and catalyzes only helicase activity.
      Helicase activity is dependent on the hydrolysis of a nucleoside 5'-triphosphate.
      Sequence analysis reveals a single "A-type" nucleoside 5'-triphosphate binding
      site near the center of each gene 4 protein. We have examined the essential role
      of nucleoside triphosphate hydrolysis both in vivo and in vitro by using site
      directed mutagenesis to alter the conserved, adjacent Gly and Lys residues within
      this nucleotide binding site. The mutant gene 4 proteins, expressed from plasmids
      carrying the cloned genes, do not complement a T7 phage lacking gene 4. Moreover,
      the mutations are dominant-lethal: they block productive infection by wild-type
      T7 phage. A nucleotide binding site mutant 56-kDa gene 4 protein, purified to
      homogeneity from cells over-expressing the gene, binds but lacks the ability to
      hydrolyze nucleotides and cannot bind to single-stranded DNA. Consequently, this
      mutant gene 4 protein also lacks helicase activity. The mutant gene 4 proteins
      inhibit the nucleotide hydrolysis activity of wild-type gene 4 proteins in a
      stoichiometric manner. The apparent inhibition constant (Ki = 22 +/- 4.5 nM) of
      this interaction may reflect the gene 4 oligomer dissociation constant in the
      presence of nucleotide and single-stranded DNA. Analysis of the inhibition
      reaction indicates that this is a linear mixed-type inhibition, indicating that
      the mutant protein binds the wild-type protein to form an inactive complex on
      single-stranded DNA. Furthermore, the mutant 56-kDa gene 4 protein has the same
      affinity for both the wild-type 63- and 56-kDa gene 4 proteins, suggesting that
      there is no preference for the formation of homo-oligomeric complexes. The
      ability of the mutant proteins to inhibit the activity of the wild-type gene 4
      proteins indicates that nucleotide hydrolysis is coordinated and cooperative
      among the members of the gene 4 protein complex as it binds and translocates on
      single-stranded DNA.

PMID- 8262962
TI  - Evidence for distinct primase and helicase domains in the 63-kDa gene 4 protein
      of bacteriophage T7. Characterization of nucleotide binding site mutant.
AB  - Gene 4 of bacteriophage T7 encodes two co-linear proteins, the 56- and 63-kDa
      gene 4 proteins. The 56-kDa protein translocates 5' to 3' on single-stranded DNA
      using nucleotide hydrolysis for energy and is a helicase. The 63-kDa gene 4
      protein catalyzes all of the activities of the 56-kDa gene 4 protein and, in
      addition, catalyzes the synthesis of oligoribonucleotides on single-stranded DNA.
      Two conserved residues in a putative nucleotide binding site of the 63-kDa gene 4
      protein were mutated by substituting Val and Met for wild-type residues Gly and
      Lys, at positions 317 and 318, respectively. The mutant 63-kDa gene 4 protein
      lacks the ability to catalyze the hydrolysis of a nucleoside 5'-triphosphate in a
      single-stranded DNA-dependent reaction and inhibits nucleotide hydrolysis by wild
      type gene 4 proteins. The mutant primase contains 0.4% of the primase activity of
      the 63-kDa gene 4 protein on M13 single-stranded DNA and 12% of the wild-type
      primase activity on an oligonucleotide with a single primase recognition site.
      Addition of wild-type 56-kDa gene 4 protein stimulates the mutant primase
      activity over 50-fold on M13 single-stranded DNA and 8-fold on oligonucleotides.
      This increase in primase activity correlates with an increase in the affinity of
      the mutant primase-wild-type helicase complex for single-stranded DNA template.

PMID- 8262963
TI  - A complex response element in intron 1 of the androgen-regulated 20-kDa protein
      gene displays cell type-dependent androgen receptor specificity.
AB  - The androgen-regulated 20-kDa protein gene consists of four exons that code for a
      major secretory protein of rat ventral prostate. Analysis of its potential cis
      acting transcriptional regulatory elements revealed that a large intron 1 region
      (In-1) had stronger androgen response element (ARE) activity than did the 5'
      flanking DNA. In cotransfected CV1 cells, In-1 and its most active subfragment In
      1c functioned as AREs but not glucocorticoid response elements (GRE).
      Nevertheless several ARE/GRE-like partial palindromic sequences are present in In
      1c, and it bound both androgen receptors and glucocorticoid receptors in mobility
      shift assays. A cluster of three ARE/GRE-like sequences contained within a 39
      base pair sequence of In-1c had both ARE and GRE activities when analyzed as an
      isolated oligonucleotide, suggesting that other elements within In-1c determined
      its ARE specificity. In addition to ARE/GRE-like sequences, In-1c contains
      putative response elements for the transcription factors AP1, CREB, AP2, OCT-1,
      C/EBP, and a number of inverted and direct repeats. The ARE specificity of In-1c
      observed in CV1 cells was diminished in PC3 and HeLa cells transiently
      cotransfected with an androgen receptor or glucocorticoid receptor expression
      vector together with an In-1c reporter vector; however, the ARE activity of In-1c
      was greater than its GRE activity in these cell lines. Interestingly, a 131-base
      pair subfragment of In-1c retained ARE specificity in all three cell lines.

PMID- 8262964
TI  - Role of the mu immunoglobulin heavy chain transmembrane and cytoplasmic domains
      in B cell antigen receptor expression and signal transduction.
AB  - Membrane immunoglobulins (mIg) serve as the recognition components of B
      lymphocyte antigen receptors. Binding of antigen to these receptors leads to
      dramatic effects on B cell growth and viability. We have examined the structural
      elements of mIgM that are involved in antigen receptor assembly and function.
      Expression of transfected wild-type mIgM in a B cell line led to assembly with
      the other two known components of the antigen receptor, Ig-alpha and Ig-beta,
      expression on the cell surface, and when cross-linked by anti-IgM antibodies,
      stimulation of signal transductin reactions, including tyrosine protein
      phosphorylation, inositol phosphate production, and increases in cytoplasmic
      calcium concentration. Replacement of the highly conserved COOH-terminal 41 amino
      acids of mIgM heavy chain (mu m) with the transmembrane and cytoplasmic domains
      of human CD8 alpha resulted in a molecule which was expressed on the B cell
      surface at levels comparable to wild-type mIgM, but which did not form a complex
      with Ig-alpha or Ig-beta and did not stimulate any of the signaling reactions
      mentioned above. Replacement of the basic three-amino-acid cytoplasmic domain of
      mu m with a different but similarly charged sequence had no effect on cell
      surface expression or signaling function. On the other hand, removal of the
      entire cytoplasmic domain resulted in a molecule which did not bind Ig-alpha and
      Ig-beta and which did not transduce signals. This effect is probably due to
      altered post-translational processing of this mutant molecule. Finally, a series
      of eight single-amino-acid substitutions in the transmembrane domain was
      constructed. Most of these resulted in the removal of hydroxyl groups from
      conserved residues postulated to be important for interactions with other
      components. Each of these mutant molecules was capable of transducing signals
      when cross-linked by anti-IgM, but one was partially defective. Since alteration
      of any single residue was not sufficient to disrupt signaling completely, the
      interactions required for signaling are likely to involve multiple residues, so
      that elimination of one hydroxyl group does not prevent the interaction. We
      propose that the cytoplasmic domain of mu m does not play a critical role in
      receptor function but that the transmembrane domain specifies interactions with
      other components, probably Ig-alpha and Ig-beta, required for proper antigen
      receptor signal transduction.

PMID- 8262965
TI  - Role of the membrane in the inactivation of factor Va by activated protein C.
AB  - Bovine factor Va inactivation by activated protein C (APC) was evaluated in the
      presence and absence of phospholipid vesicles and protein S. Following a 30-min
      incubation with APC (10 nM), membrane-bound factor Va (200 nM) is completely
      inactivated, whereas in the absence of phospholipid vesicles, after a 2-h
      incubation, the cofactor retains 60% of its initial cofactor activity. The
      complete loss of activity of membrane-bound factor Va is associated with the
      appearance of M(r) 40,000, 28,000, and 20,000 fragments derived from the heavy
      chain of the cofactor which correspond to cleavage at Arg306, Arg505, and Arg662.
      In the absence of a lipid bilayer, cleavage at Arg505 and Arg662 results in a
      cofactor with reduced activity. No difference is observed in the cleavage of the
      light chain of the cofactor by APC in the presence or absence of phospholipid
      vesicles. The rate of the cleavage of factor Va heavy chain at Arg306, Arg505,
      and Arg662 as well as the rate of the membrane-bound cofactor inactivation by APC
      were enhanced in the presence of protein S. Our data demonstrate that the anionic
      lipid-dependent cleavage of factor Va by APC at Arg306 is required for the
      complete inactivation of the cofactor.

PMID- 8262966
TI  - Negative regulation of the gene for H-2Kb class I antigen by adenovirus 12-E1A is
      mediated by a CAA repeated element.
AB  - Both positive and negative regulatory elements responsive to the product of the
      adenovirus type 12 E1A gene are located in the promoter region of the gene for
      mouse H-2Kbm1 major histocompatibility complex (MHC) class I antigen (1). We have
      analyzed the negative regulatory element that is affected by E1A and identified a
      target CAA repeated motif, CAA(A)CAAA, within -1725 to -1705 and -1591 to -1568
      in a 316-bp sequence located in the far upstream region of H-2Kb promoter (-1837
      to -1522; +1 refers to the cap site). The extent of cell surface expression of
      the MHC class 1 antigen was significantly decreased in the case of transfectants
      obtained by introducing an expression plasmid that included MHC class 1 cDNA with
      the CAA repeated element, as compared with that of a plasmid with mutated CAA
      repeats. We have also characterized the nuclear proteins that bind to this motif.
      The analysis of the effects of mutations during competition assays of in vivo and
      gel retardation competition assays demonstrated that the CAA repeated element is
      essential not only for E1A-dependent repression of transcription but also for the
      cell surface expression of the product of the mouse H-2Kb class I gene,
      presumably through nuclear proteins that specifically bind to it.

PMID- 8262967
TI  - Tracing intracellular proteolytic pathways. Proteolysis of fatty acid synthase
      and other cytoplasmic proteins in the yeast Saccharomyces cerevisiae.
AB  - Yeast fatty acid synthase consists of two independent polypeptide strains, alpha
      and beta. The functional multienzyme complex, composed of six alpha- and six beta
      subunits, is rather stable against proteolysis in vivo. Mutations in one of the
      subunits or deletion of one subunit lead to degradation of the nonmutated
      remaining fatty acid synthase protein. We show that the unassembled alpha-subunit
      of this enzyme is short-lived, and degradation depends on the presence of active
      cytoplasmic proteinase yscE, the yeast proteasome. The unassembled beta-subunit
      is degraded by a nonvacuolar proteolytic system under vegetative growth
      conditions. However, starvation of a vacuolar proteinase mutant strain, which
      lacks the alpha-subunit of fatty acid synthase, leads to appearance of the
      unassembled beta-subunit is isolated vacuoles. This indicates that the major
      vacuolar peptidases proteinase yscA and yscB are at least partly involved in
      degradation of the beta-subunit of fatty acid synthase. In a proteinase yscA and
      yscB double mutant strain wild type for fatty acid synthase both subunits of
      fatty acid synthase, alpha and beta, are detectable in vacuoles. In addition,
      under the same starvation conditions other cytoplasmic proteins are found in the
      vacuole of a proteinase yscA and yscB double mutant strain. The experiments in
      conjunction with the previous finding of the appearance of vesicles in vacuoles
      of starved cells (Simeon, A., van der Klei, I.J., Veenhuis, M., and Wolf, D. H.
      (1992) FEBS Lett. 301, 231-235) indicate that transport of these tested
      cytoplasmic proteins into the vacuole is an unselective bulk process induced by
      nutritional stress.

PMID- 8262968
TI  - Regulation of human ornithine decarboxylase expression by the c-Myc.Max protein
      complex.
AB  - The presence of a CACGTG element within a region of the human ornithine
      decarboxylase (ODC) promoter located at -491 to -474 base pairs 5' to the start
      site of transcription suggested that the c-Myc.Max protein complex may play a
      role in the regulation of ODC expression during growth. Electrophoretic mobility
      shift assays and methylation interference analysis showed that the nuclei of WI
      38 cells expressing ODC contained proteins that bound to this region of the ODC
      gene in a manner that correlated with growth-associated ODC expression. Also, use
      of antibodies against c-Myc and Max and purified recombinant c-Myc and Max
      protein in the electrophoretic mobility shift assay confirmed that these proteins
      can specifically bind this portion of the human ODC promoter. Transient
      transfection studies showed that increase in the level of c-Myc and/or Max led to
      a significant enhancement of expression of a human ODC promoter-CAT reporter
      construct. Moreover, treatment of actively growing WI-38 cells with an antisense
      oligomer to c-Myc reduced the amount of endogenous protein complex formed and the
      amount of endogenous ODC mRNA expressed. These studies show that the c-Myc.Max
      protein complex plays a role in the transcriptional regulation of human ODC in
      vivo.

PMID- 8262969
TI  - The human active breakpoint cluster region-related gene encodes a brain protein
      with homology to guanine nucleotide exchange proteins and GTPase-activating
      proteins.
AB  - GTPase-activating proteins (GAPs) modulate the activity of the ras superfamily of
      proteins by converting active GTP-bound to inactive GDP-bound p21s. Employing a
      novel GAP overlay assay (Manser, E., Leung, T., Monfries, C., Teo, M., Hall, C.,
      and Lim, L. (1992) J. Biol. Chem. 267, 16025-16028), we demonstrated a diversity
      of proteins with GAP activities in different tissues. Using a polymerase chain
      reaction strategy exploiting conserved residues in the GAP domains of n-chimaerin
      and the product of the breakpoint cluster region gene (BCR), we isolated a human
      brain 5.3-kilobase cDNA containing a 486-base pair region with complete identity
      to a previously reported active BCR-related (ABR) gene sequence on human
      chromosome 17. The brain cDNA encoded a 98-kDa protein (ABR) resembling BCR (68%
      identity), containing both the oncogene dbl-related domain at the N terminus and
      the GAP domain at the C terminus; however, it lacks the N-terminal BCR protein
      kinase domain. The ABR GAP domain expressed as an Escherichia coli fusion protein
      was active against Rac1 and Cdc42 of the rho subfamily. The ABR mRNA is highly
      enriched in the brain. ABR probably corresponds to the brain-enriched 100-kDa GAP
      for Rac and Cdc42Hs previously detected. The relationship of ABR to Miller-Dieker
      syndrome, a neurological disorder co-mapping to 17p13.3, is discussed.

PMID- 8262970
TI  - Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo
      sphingolipid biosynthesis in cultured neurons in situ.
AB  - Fumonisins, mycotoxins produced by Fusarium moniliforme and a number of other
      fungi, cause neuronal degeneration, liver and renal toxicity, cancer, and other
      injury to animals. Recent work with rat hepatocytes (Wang, E., Norred, W. P.,
      Bacon, C. W., Riley, R. T., and Merrill, A. H., Jr. (1991) J. Biol. Chem. 266,
      14486-14490) found that fumonisins block sphingosine biosynthesis by inhibiting
      the conversion of sphinganine to dihydroceramides, which precedes introduction of
      the 4,5-trans-double bond of sphingosine. The current study utilized mouse
      cerebellar neurons in culture to evaluate how this affects the distribution of
      newly synthesized ceramides among different complex sphingolipids. Fumonisin B1
      inhibited ceramide synthase in mouse brain microsomes with a competitive-like
      kinetic behavior with respect to both sphinganine and stearoyl-CoA. Fumonisin B1
      inhibited sphingolipid biosynthesis in cultured cerebellar neurons in situ as
      reflected by accumulation of free sphinganine, a reduction in the mass of total
      sphingolipids, reductions in the incorporation of [14C]serine into
      glucosylceramide, lactosylceramide, sphingomyelin, and gangliosides (GM1, GD3,
      GD1a, GD1b, GT1b, and GQ1b), and inhibition of the incorporation of
      [14C]galactose and [3H]sphinganine into complex sphingolipids. Dose-response
      studies revealed that the labeling of sphingomyelin (IC50 of 0.7 microM) was more
      sensitive to inhibition by fumonisin B1 than was glycolipid formation (IC50 of
      approximately 7 microM) in these cells. A similar effect was seen when beta
      fluoroalanine was added to inhibit the activity of serine palmitoyltransferase,
      the first enzyme of the pathway. The inhibition of complex sphingolipid synthesis
      was reversible, and nearly normal labeling profiles were obtained 48 h after
      removing the mycotoxin. These studies establish that fumonisin B1 inhibits de
      novo sphingolipid biosynthesis by neuronal cells and, moreover, that limiting
      ceramide synthesis differentially affects the formation of sphingomyelin versus
      glycosphingolipids.

PMID- 8262971
TI  - Binding of fibromodulin and decorin to separate sites on fibrillar collagens.
AB  - The small proteoglycans, decorin, fibromodulin, biglycan, and lumican, represent
      a family of structurally related but genetically distinct molecules present in
      many types of connective tissues. Fibromodulin and decorin interact with
      collagens I and II (Hedbom, E., and Heinegard, D. (1989) J. Biol. Chem. 264, 6898
      6905). These interactions have been characterized further by using native
      radiolabeled components from fibroblast cultures and nonlabeled proteoglycans
      purified from guanidine hydrochloride extracts of bovine tendon. Binding of
      metabolically labeled macromolecules to collagen I was measured in an assay based
      on precipitation of collagen fibrils formed in vitro. Among a large number of
      secreted fibroblast products, decorin and fibromodulin represented the vast
      majority of the collagen binding components. These molecules showed poor binding
      to denatured collagen, in contrast to fibronectin, which was also present in the
      medium. Decorin and fibromodulin bind to different sites on collagen I fibrils,
      since the binding of either radiolabeled component could be competed for only by
      the corresponding nonlabeled proteoglycan. Similarly, these proteoglycans showed
      binding to separate sites on collagen II. Binding of isolated fibromodulin and
      decorin to collagens in solution was measured in a solid-phase inhibition assay.
      Each of the proteoglycans interacted with triple helical molecules, but not with
      denatured collagen chain constituents or fragments. For fibromodulin, the data
      indicated an average of one binding site per collagen I molecule (Kd = 9.9 nM).
      The data on decorin indicated additional interactions, some apparently mediated
      by the dermatan sulfate side chain. The results suggest that the small
      proteoglycans bind to distinct triple helical sites, apparently differing from
      several other similar structures within each collagen molecule.

PMID- 8262972
TI  - Characterization of a second RNA-binding protein in rodents with specificity for
      iron-responsive elements.
AB  - Iron regulatory factor (IRF) is a cytoplasmic RNA-binding protein involved in
      regulating iron homeostasis. IRF controls expression of ferritin and transferrin
      receptor post-transcriptionally via specific binding to stem-loop iron-responsive
      elements (IREs) located in the untranslated regions of the respective mRNAs. We
      have confirmed by RNA band-shift analysis that a second IRE-protein complex
      observed in different rodent cell extracts is, like IRF, regulated by
      intracellular iron levels. This faster migrating complex appears to represent a
      specific interaction between the ferritin IRE and an iron-regulated protein that
      is distinct from IRF, as concluded from the following lines of evidence. First,
      UV cross-linking and partial digestion with different proteases revealed
      different peptide patterns for the two IRE-protein complexes. Second, antiserum
      raised against IRF peptides immunoprecipitated only authentic IRF and not the
      protein of the faster migrating complex, as determined by band-shift analysis.
      Following separation of the two IRE-binding proteins by ion-exchange
      chromatography, only the IRF-containing fraction reacted with the antibodies on
      Western blots. The second protein binds IREs with an affinity similar to that of
      IRF as demonstrated by competition with a ferritin IRE and related stem-loop
      RNAs. UV cross-linking experiments indicate that this second protein, tentatively
      named IRFB, has a molecular mass of approximately 105 kDa. Analysis of mouse
      tissues revealed differences in the distribution of IRF and IRFB. Whereas IRF
      protein and IRE binding activity were predominant in liver, intestine, and
      kidney, the IRFB protein(s) revealed highest binding activity in intestine and
      brain. Our data support the existence of two distinct iron-regulated IRE-binding
      proteins in rodents.

PMID- 8262973
TI  - Arachidonic acid and endothelin potentiate Ca2+ transients in rat cardiac
      myocytes via inhibition of distinct K+ channels.
AB  - The release of arachidonic acid by phospholipases in response to cell surface
      receptor activation may be an important step in the initiation of inotropic
      events in cardiac muscle. Endothelin has been shown to activate phospholipase A2
      and release arachidonic acid in isolated rat hearts. Endothelin also has a
      positive inotropic effect in cardiac muscle, suggesting that endothelin increases
      Ca2+ influx or the amount of Ca2+ released from the sarcoplasmic reticulum. We
      used suspensions of adult rat ventricular myocytes loaded with fura-2/AM to
      compare the effects of arachidonic acid and endothelin on Ca2+ transients evoked
      by extracellular ATP. We showed recently (Damron, D.S., and Bond, M. (1993) Circ.
      Res. 72, 376-386) that pretreatment of cardiac myocytes with arachidonic acid
      significantly potentiated the amplitude of the ATP-triggered Ca2+ transient. We
      now report that endothelin also enhances the ATP-triggered Ca2+ transient and
      that the effect of the combination of maximal doses of endothelin and arachidonic
      acid is additive. Neither endothelin nor arachidonic acid was found to affect the
      size of the sarcoplasmic reticulum Ca2+ store. The potentiating effects of both
      arachidonic acid and endothelin were sensitive to inhibitors of protein kinase C.
      Endothelin was also found to stimulate phospholipase C but not phospholipase A2.
      Application of arachidonic acid to individual cardiac muscle cells resulted in
      inhibition of the transient outward K+ current, whereas application of endothelin
      inhibited the delayed rectifier current. These effects of arachidonic acid and
      endothelin were additive, and both effects could be blocked by the protein kinase
      C inhibitor, staurosporine. Similarly, staurosporine inhibited endothelin-induced
      increases in isometric contractions in ventricular papillary muscle. We conclude
      that arachidonic acid and endothelin may be involved in the modulation of
      inotropic activity in cardiac muscle by means of protein kinase C-dependent
      inhibition of two distinct K+ channels. This would result in a prolongation of
      action potential duration and thus an increase in Ca2+ influx across the
      sarcolemma.

PMID- 8262974
TI  - Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, blocks
      lysosomal cholesterol trafficking in macrophages.
AB  - Certain steroids having an oxo group at the C-17 or C-20 position such as
      pregnenolone and dehydroisoandrosterone inhibit the cholesterol transport from
      lysosomes to other cellular sites. Taking advantage of the fact that the
      inhibition is reversed upon removal of the steroids, we studied the factors that
      control the cholesterol transport from lysosomes to other cellular sites in
      macrophages. Macrophages that accumulated unesterified cholesterol in their
      lysosomes were prepared by incubating cells with liposomes containing cholesterol
      and phosphatidylserine in the presence of a steroid inhibitor. These cells were
      chased by means of steroid washout, and then the effects of various
      pharmacological agents on the subsequent metabolism of cholesterol were examined.
      When the cells were chased in the absence of the agents, some of the cholesterol
      was converted to cholesteryl esters in the cells, and others were desorbed into
      the medium as unesterified forms, suggesting recovery of lysosomal cholesterol
      trafficking. Among the agents tested, bafilomycin A1, a specific inhibitor of
      vacuolar-type H(+)-ATPase, completely blocked both cholesterol esterification and
      cholesterol desorption at 10 nM. Moreover, agents that neutralize the lysosomal
      proton gradient, such as ammonium chloride and chloroquine, also reduced both of
      the processes. Fluorescent microscopic examination of bafilomycin A1-treated
      cells revealed extensive filipin-cholesterol staining of perinuclear lysosomes.
      From these data, we conclude that acidic pH is required for the efflux of
      cholesterol from lysosomes to other cellular sites.

PMID- 8262975
TI  - A serine and a lysine residue implicated in the catalytic mechanism of the
      Escherichia coli leader peptidase.
AB  - We report that a thiol leader peptidase, produced by replacing the critical
      serine at position 90 with a cysteine residue, is enzymatically active. In
      contrast to the wild-type leader peptidase, the thiol enzyme can be inactivated
      with N-ethylmaleimide, a cysteine-specific reagent. This strongly suggests that
      the serine 90 is involved in catalysis and is located at the active site. Of the
      three conserved basic residues in the signal peptidase family, only lysine 145
      appears to be critical for catalysis; when lysine 145 was mutated to an alanine
      residue, leader peptidase K145A protein was inactive both in vitro and in vivo. A
      control experiment showed that the K145A mutant competes with the wild-type
      leader peptidase for substrate binding, confirming that the K145A mutation did
      not cause a global conformational change. The data provides evidence that
      catalysis of leader peptidase is carried out by a serine-lysine dyad.

PMID- 8262976
TI  - Identification of the sites of selective phosphorylation and dephosphorylation of
      the rat brain Na+ channel alpha subunit by cAMP-dependent protein kinase and
      phosphoprotein phosphatases.
AB  - Voltage-sensitive brain Na+ channels are regulated by cAMP-dependent protein
      kinase (cA-PK) and protein kinase C. Using synthetic peptides and protein
      microsequencing, we have determined that the alpha subunit of rat brain Na+
      channel is selectively phosphorylated by cA-PK in vitro and in intact cells on 4
      serine residues in the intracellular loop connecting homologous domains I and II.
      Ser-623 was most rapidly and extensively phosphorylated in vitro, whereas Ser
      573, Ser-610, and Ser-687 were phosphorylated to lesser extents. In contrast,
      serine 687 was most extensively phosphorylated in mammalian cells transfected
      with the alpha subunit of type IIA Na+ channel in response to an increase in
      intracellular cAMP. Purified protein phosphatases dephosphorylated these sites
      selectively. Calcineurin rapidly and extensively dephosphorylated Ser-623 and
      also dephosphorylated Ser-573, Ser-610, and Ser-687 to lesser extents.
      Phosphatase 2A selectively dephosphorylated Ser-610. Together these results
      indicate that modulation of neuronal Na+ channel activity and therefore neuronal
      excitability by cAMP-dependent phosphorylation results from selective
      phosphorylation and dephosphorylation of four sites in the intracellular loop
      connecting homologous domains I and II of the alpha subunit.

PMID- 8262977
TI  - Iron-responsive element-binding protein. Phosphorylation by protein kinase C.
AB  - The iron-responsive element-binding protein (IRE-BP) is a cytosolic RNA-binding
      protein that functions in the maintenance of iron homeostasis by post
      transcriptionally regulating transferrin receptor and ferritin synthesis. Little
      is known concerning how factors other than iron may modulate the activity of this
      central regulator of cellular iron utilization. We present evidence indicating
      that phosphorylation of the IRE-BP by protein kinase C (PKC) could provide a
      mechanism for regulation of IRE-BP function. Purified rat liver IRE-BP was
      phosphorylated by PKC up to 1.3 mol of phosphate/mol of protein with Ser the
      modified amino acid. Ser was also the phosphoacceptor in the IRE-BP in intact
      cells. The Km of PKC for the IRE-BP was 0.4 microM. Tryptic phosphopeptide
      mapping identified one major phosphopeptide plus several other peptides with
      lesser amounts of phosphate. Synthetic peptides of the IRE-BP containing Ser 138
      (site A) and Ser 711 (site B) were phosphorylated by PKC. In HL 60 cells,
      addition of phorbol 12-myristate 13-acetate (PMA) stimulated IRE-BP
      phosphorylation within 30 min and increased high affinity IRE RNA binding
      activity 2-fold. After 90 min, the level of phosphorylation had increased
      further, and high affinity IRE RNA binding activity had increased 3-fold above
      the control. Incorporation of [35S]Met into immunoprecipitable IRE-BP was not
      altered in cells treated with PMA for 30 or 90 min. PMA also stimulated IRE-BP
      phosphorylation in rat fibroblasts. Taken together, our studies begin to define a
      novel mechanism by which hormones, growth factors, and other agents may regulate
      cellular iron utilization through specific phosphoregulation of the IRE-BP.

PMID- 8262979
TI  - Structure, chromosomal localization, and expression pattern of the murine Magp
      gene.
AB  - The microfibril-associated glycoprotein (MAGP) was recently established as a
      discrete constituent of 10-nm microfibrils. We have characterized the primary
      structure of the mouse transcript, the structure and chromosomal localization of
      the murine gene, and the developmental pattern of gene expression. The transcript
      consists of 1,037 base pairs as determined by cDNA cloning, Northern blot
      analysis, S1 nuclease mapping, and primer extension mapping. Using a cDNA
      fragment as a probe, we isolated a single genomic clone that contained the entire
      mouse gene. Analysis of this clone indicated that Magp is fragmented into 9
      exons, with the initiator Met codon located in exon 2. As determined by analysis
      of somatic cell hybrid lines and by fluorescence in situ hybridization, the mouse
      gene was mapped to chromosome 4 at a location corresponding to region D3-E1.
      Genomic sequence immediately upstream of the transcription start site was found
      to be GC-rich but lacked TATA or CCAAT boxes as well as other cis-acting motifs
      known to regulate transcription. Promoters of this type are usually found in
      genes that exhibit broad temporal and spatial patterns of expression. Consistent
      with this idea, the Magp transcript appeared to be the widespread product of
      mesenchymal/connective tissue cells throughout mouse development. This study
      presents the first comprehensive evaluation of microfibril gene expression during
      mammalian development.

PMID- 8262978
TI  - Cloning of the promoter for the avian integrin beta 3 subunit gene and its
      regulation by 1,25-dihydroxyvitamin D3.
AB  - We have cloned the promoter of the avian beta 3 integrin gene. Using a probe
      comprising the 5'-untranslated region of an avian macrophage beta 3 cDNA,
      characterized by 5' rapid amplification of cDNA ends, several clones were
      isolated from an avian genomic library. One major and one minor transcriptional
      start site were identified at +1 and -47 base pairs, respectively, with the
      latter coinciding with a consensus sequence of an initiator. DNA sequence
      analysis of 800 base pairs 5' of the transcriptional start site fails to reveal
      either a TATA or CAAT box. In addition to an initiator, the first 200 base pairs
      contain consensus sequences for the binding of AP-1 and SP-1. A 3.5-kilobase
      fragment located immediately upstream of the transcriptional start site exhibits
      functional promoter activity, and deletion analysis reveals both suppressor and
      enhancer elements. In light of our observation that 1,25-dihydroxyvitamin D3 (D3)
      accelerates beta 3 transcription, we determined whether the avian beta 3 promoter
      contains a vitamin D response element (VDRE). Transfected reporter constructs
      containing the first 1.5 kilobases upstream of the major beta 3 transcriptional
      start site respond to D3 with enhanced luciferase activity. Analysis of this
      region reveals a classical VDRE consensus sequence, located at -756 to -770. The
      following observations support the hypothesis that this sequence represents a
      functional VDRE: 1) a 600-base pair genomic fragment or a 29-base pair oligomer,
      each containing the putative VDRE, respond to D3 when transfected into HD11
      cells; 2) a 67-base pair DNA fragment derived from genomic DNA and containing the
      candidate beta 3 VDRE specifically binds the vitamin D receptor-retinoid X
      receptor beta complex; and 3) avian osteoclast precursor-derived nuclear extracts
      bind to a synthetic oligomer containing the beta 3 VDRE-like sequence and, in
      turn, are specifically displaced by unlabeled beta 3 VDRE and anti-vitamin D
      receptor antibody.

PMID- 8262980
TI  - Evidence that the Gh protein is a signal mediator from alpha 1-adrenoceptor to a
      phospholipase C. I. Identification of alpha 1-adrenoceptor-coupled Gh family and
      purification of Gh7 from bovine heart.
AB  - Our previous studies on alpha 1-adrenoceptor-mediated signaling suggested that Gh
      is a signal mediator. Gh consists of a 74-kDa GTP-binding alpha-subunit and a 50
      kDa beta-subunit. Studies using the alpha 1-agonist-receptor-G-protein ternary
      complexes from various tissues and species revealed that the intensity (GTP
      binding) of the [alpha-32P]GTP-labeled proteins resulting from activating the
      alpha 1-receptor was significantly attenuated by phentolamine. The molecular
      masses of GTP-binding proteins were 74 kDa in rat heart and liver, 77 kDa in dog
      heart, 78 kDa (Gh7 alpha) in bovine heart and liver, and 80 kDa in human heart.
      Supporting these observations, a specific antibody to Gh7 alpha not only
      recognized these GTP-binding proteins in the ternary complex preparations, but
      also co-immunoprecipitated alpha 1-adrenoceptors, indicating a tight association
      of these GTP-binding proteins with the alpha 1-adrenoceptor. These results also
      demonstrate that functional and structural similarities exist among these GTP
      binding proteins. Additionally, one of the identified G-proteins (termed Gh7) was
      purified from bovine heart. Gh7 consisted of the 78-kDa GTP-binding protein and a
      50-kDa protein.

PMID- 8262981
TI  - Evidence that the Gh protein is a signal mediator from alpha 1-adrenoceptor to a
      phospholipase C. II. Purification and characterization of a Gh-coupled 69-kDa
      phospholipase C and reconstitution of alpha 1-adrenoceptor, Gh family, and
      phospholipase C.
AB  - Our studies on the alpha 1-adrenoceptor signaling have demonstrated that the Gh
      family is a signal mediator. We report here that a 69-kDa phospholipase C (PLC)
      is the effector in this signal pathway. The enzyme was isolated by dissociating a
      Gh7-PLC complex which was induced in the bovine liver membranes incubating with (
      )-epinephrine and GTP. The enzyme displayed a marked preference hydrolysis for
      phosphatidylinositol 4,5-bisphosphate over other phosphatidylinositides at
      micromolar calcium. Reconstitution of PLC with the alpha 1-adrenoceptor and Gh
      (Gh7) into phospholipid vesicles resulted in a lowered Ca2+ requirement for the
      substrate hydrolysis in the presence of guanosine 5'-3-O-(thio)triphosphate (GTP
      gamma S) when the receptor was activated with the alpha 1-agonist. The formation
      of inositol phosphate was hormone concentration dependent and reached maximal
      within 3 min which was faster than the formation in the presence of the alpha 1
      antagonist. An Gh7 alpha antibody co-immunoprecipitated 80-85% of phospholipase C
      activity in the presence of GTP gamma S, but not in the presence of GDP or
      buffer, showing the association of PLC with the alpha-subunit of Gh family. Thus,
      our novel approaches to identify the effector involved in the alpha 1
      adrenoceptor signaling, as well as the reconstitution studies, substantially
      demonstrate that the alpha 1-adrenoceptor-mediated transmembrane signaling
      involves the Gh family and a 69-kDa PLC.

PMID- 8262982
TI  - Down-regulation of mRNA for the low density lipoprotein receptor in transgenic
      mice containing the gene for human cholesteryl ester transfer protein. Mechanism
      to explain accumulation of lipoprotein B particles.
AB  - To evaluate the effects of cholesteryl ester transfer protein (CETP) on apoB
      containing lipoproteins, we analyzed plasma lipoproteins from three different
      lines of human CETP transgenic mice, with plasma CETP concentration ranging from
      low (1.5 microgram/ml) to high levels (8.5 micrograms/ml). With increasing CETP
      concentration, very low density lipoprotein and low density lipoprotein (LDL)
      cholesteryl ester (CE) and apoB were progressively increased, and high density
      lipoprotein CE was decreased. To investigate the mechanism of accumulation of
      lipoproteins containing apoB (lipoprotein B), the abundance of hepatic LDL
      receptor mRNA was determined. LDL receptor mRNA was reduced as a result of CETP
      expression, with maximum repression to about 48% of the level of non-transgenic
      mice. Among the different lines of CETP transgenic mice there was an inverse
      relationship between plasma CETP concentration and hepatic LDL receptor mRNA
      abundance (r = -0.94, p < 0.01). CETP expression also led to increased
      cholesterol and cholesteryl ester content in liver and to decreased abundance of
      mRNAs encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase and 7-alpha
      hydroxylase. Thus, CETP expression results in increased cholesteryl ester
      concentration in very low density lipoprotein and LDL, probably reflecting both
      CE transfer from high density lipoprotein and accumulation of lipoprotein B
      particles. The accumulation of lipoprotein B particles results from CETP-mediated
      down-regulation of liver LDL receptors, possibly due to enhanced return of
      cholesterol to the liver.

PMID- 8262983
TI  - Functional and physical interaction of protein-tyrosine kinases Fyn and Csk in
      the T-cell signaling system.
AB  - The Src-like protein-tyrosine kinase Fyn is associated with T-cell antigen
      receptor. Transient expression of actively mutated Fyn, having Phe-528 instead of
      Tyr-528 or Thr-338 instead of Ile-338, in Jurkat T-cells stimulated the serum
      response element (SRE), 12-O-tetradecanoyl-phorbol-13-acetate response element,
      cyclic AMP response element, and c-fos promoter. The stimulation of SRE was
      particularly prominent not only with active Fyn but also with normal (wild-type)
      Fyn. SRE was also stimulated by both normal and active Lck. Furthermore, normal
      and active Fyn stimulated transcription from the IL-2 gene promoter when
      transfected cells were stimulated by concanavalin A plus 12-O
      tetradecanoylphorbol-13-acetate. Under the same conditions, Lck did not stimulate
      IL-2 promoter unless it was activated by mutation. Interestingly, a mutant Fyn,
      which has deletions within the SH2 region and so is able to transform chicken
      embryo fibroblasts, did not stimulate either the c-fos or IL-2 promoter,
      suggesting the importance of this region in T-cell signaling. Csk, which
      phosphorylates tyrosine residues in the negative regulatory sites of Src family
      kinases, down-regulated Fyn- and Lck-mediated stimulation of the serum response
      element and Fyn-mediated enhancement of IL-2 promoter activity. These data
      suggest that Fyn and Lck, whose activities are regulated by Csk, are involved in
      different phases of T-cell activation.

PMID- 8262984
TI  - Anti-CD3 and phorbol ester induce distinct phosphorylated sites in the SH2 domain
      of p56lck.
AB  - P56lck is a protein tyrosine kinase of the Src family specifically expressed in T
      lymphocytes. Triggering of T cells with anti-CD3 or with phorbol 12-myristate 13
      acetate (PMA) results in the appearance of slower migrating forms (shift) of
      p56lck. To investigate the phosphorylation sites on the shifted forms of p56lck
      and to assess the role of protein kinase C in this phosphorylation, Jurkat cells
      were treated with a selective inhibitor of this kinase (GF 109203X). This
      inhibitor completely reversed the shift induced by PMA but only partially
      reversed the one induced after triggering with anti-CD3. To analyze the shift
      further, p56lck was immunoprecipitated from in vivo labeled cells treated either
      with anti-CD3 or with PMA. Tryptic phosphopeptides were generated and analyzed by
      using a combination of thin layer chromatography, high reticulation
      polyacrylamide gel electrophoresis, reverse phase chromatography, and
      phosphopeptide sequencing. We identified serine 158 as a newly phosphorylated
      site after PMA treatment and tyrosine 192 and serine 194 in the major tryptic
      phosphopeptide obtained after anti-CD3 triggering. The three sites identified are
      located in the SH2 domain of p56lck; this suggests that their phosphorylation may
      regulate the interaction with other proteins or with other internal domains in
      p56lck.

PMID- 8262985
TI  - The ethanol-inducible YAT1 gene from yeast encodes a presumptive mitochondrial
      outer carnitine acetyltransferase.
AB  - The gene YAT1 from Saccharomyces cerevisiae encodes a protein of 688 amino acids
      which displays significant sequence similarity to vertebrate L-carnitine
      acyltransferases and yeast inner mitochondrial L-carnitine acetyltransferase.
      Steady state levels of the respective mRNA are low during growth on glucose or
      galactose, derepressed on glycerol, and significantly induced when ethanol or
      acetate are the only carbon sources. The YAT1 promotor region confers the
      identical carbon source dependence also on the expression of beta-galactosidase
      when cloned 5' to the Escherichia coli lacZ-coding region. An antiserum directed
      against a beta-galactosidase/Yat1p fusion protein recognizes a protein of 78-kDa
      molecular mass in the mitochondrial fraction from yeast. In vitro translated
      Yat1p, which lacks a cleavable presequence, binds to mitochondria in a protease
      sensitive location in a standard in vitro import assay. Deletion of the single
      copy gene in a haploid yeast strain yields no obvious phenotype with any carbon
      source. Carnitine acetyltransferase activities of intact mitochondria from a YAT1
      deletion mutant are slightly lower than wild type, but are approximately alike in
      lysed mitochondria from mutant and control cells. Thus, the novel gene is
      nonessential and likely to code for a minor mitochondrial outer carnitine
      acetyltransferase.

PMID- 8262986
TI  - Multiple cDNA sequences of bovine tracheal lysozyme.
AB  - The principal role of lysozyme is to prevent bacterial invasion at body surfaces.
      We are interested in how lysozyme is regulated at the surface of the respiratory
      tract, where the serous gland cell is regarded as the primary cellular source of
      this enzyme. Since the cow genome contains at least 10 lysozyme-like genes, our
      objective was to determine which of them are expressed in the cow tracheal gland
      serous cell. By screening tracheal cDNA libraries with a probe constructed from
      the cDNA encoding stomach lysozyme 2, we obtained 3 lysozyme cDNAs: 5a (1023 base
      pairs (bp)), 7a (1060 bp), and 14d (1249 bp). cDNA 7a corresponds to a previously
      reported gene (showing sequence identity to the stomach 2 lysozyme gene), whereas
      cDNAs 5a and 14d correspond to lysozyme genes not previously reported. Northern
      blot analysis of cow tracheal RNA showed lysozyme mRNAs of three distinct
      lengths. Based on hybridization with probes specific for each cDNA, we determined
      that the longest transcript corresponded to cDNA 5a, the shortest to 7a, and the
      intermediate-length transcript to 14d. Cultured cow tracheal gland serous cell
      RNA, reverse transcribed and amplified by the polymerase chain reaction with
      primers common to all three cDNAs, yielded a product that hybridized to
      oligonucleotide probes specific for all three cDNAs but most strongly to that for
      5a. These results indicate that multiple lysozyme mRNAs are expressed in the cow
      trachea and that the lysozyme encoded by cDNA 5a is the major form expressed in
      the tracheal gland serous cell. This serous cell lysozyme is predicted to differ
      importantly in structure from both 7a and 14d lysozymes, with an arginine:lysine
      ratio almost 10-fold higher. The sequence differences may underlie functional
      differences, including variable resistance to proteolysis and variable affinity
      for large polyanions (e.g. mucins) found in the respiratory tract lumen.

PMID- 8262987
TI  - Structural and functional importance of a conserved hydrogen bond network in
      human carbonic anhydrase II.
AB  - Amino acid substitutions at Thr199 of human carbonic anhydrase II (CAII) (Thr199-
      >Ser, Ala, Val, and Pro) were characterized to investigate the importance of a
      conserved hydrogen bonding network. The three-dimensional structures of azide
      bound and sulfate-bound T199V CAIIs were determined by x-ray crystallographic
      methods at 2.25 and 2.4 A, respectively (final crystallographic R factors are
      0.173 and 0.174, respectively). The CO2 hydrase activities of T199S and T199P
      variants suggest that the side chain methyl and backbone amino functionalities
      stabilize the transition state by approximately 0.4 and 0.8 kcal/mol,
      respectively. The side chain hydroxyl group causes: stabilization of zinc
      hydroxide relative to zinc-water (pKa increases approximately 2 units);
      stabilization of the transition state for bicarbonate dehydration relative to the
      CAII.HCO3- complex (approximately 5 kcal/mol); and destabilization of the
      CAII.HCO3- complex (approximately 0.8 kcal/mol). An inverse correlation between
      log(kcatCO2/KM) and the pKa of zinc-water (r = 0.95, slope = -1) indicates that
      the hydrogen bonding network stabilizes the chemical transition state and zinc
      hydroxide similarly. These data are consistent with the hydroxyl group of Thr199
      forming a hydrogen bond with the transition state and a non-hydrogen-bonded van
      der Waals contact with CAII.HCO3-.

PMID- 8262988
TI  - Material coefficients of the strain energy function of pulmonary arteries in
      normal and cigarette smoke-exposed rats.
AB  - The effect of cigarette smoke on the stress-strain relationship of pulmonary
      arteries was studied in 2- and 3-month smoke-exposed rats. The animals were
      exposed to cigarette smoke in a smoke-generating system 10 times daily with one
      cigarette each time. The smoke density and the puffing duration and frequency of
      the system were regulated in accordance with reference values measured from human
      smokers. The mechanical properties of the pulmonary arteries about 450 microns in
      external diameter (at zero pressure) were determined in vitro by inflation and
      deflation tests. The average stress and middle-wall strain of the selected
      pulmonary arteries were determined on the basis of experimental data including
      inflation and deflation pressures during loading and unloading processes,
      respectively, and vessel diameter and length at various pressure levels, and
      vessel circumferential and longitudinal lengths at zero-stress state. A
      constitutive equation for the pulmonary arteries was derived from an energy
      function depending on circumferential and longitudinal Green's strains. The
      coefficients of the strain energy function of the pulmonary arteries were
      determined in both the smoke-exposed and control rats by fitting the experimental
      stress-strain data with the constitutive equation. It was found that the wall
      stress of the pulmonary arteries at a given strain and most of the coefficients
      of the strain energy function were increased in both the 2- and 3-month smoke
      exposed rats in comparison with those in the corresponding controls. These
      results indicated that cigarette smoke induced an increase in the wall stiffness
      of the pulmonary arteries in the rats.

PMID- 8262989
TI  - Quantitative analysis of bone reactions to relative motions at implant-bone
      interfaces.
AB  - Connective soft tissues at the interface between implants and bone, such as in
      human joint replacements, can endanger the stability of the implant fixation. The
      potential of an implant to generate interface bone resorption and form soft
      tissue depends on many variables, including mechanical ones. These mechanical
      factors can be expressed in terms of relative motions between bone and implant at
      the interface or deformation of the interfacial material. The purpose of this
      investigation was to determine if interface debonding and subsequent relative
      interface motions can be responsible for interface degradation and soft tissue
      interposition as seen in experiments and clinical results. A finite element
      computer program was augmented with a mathematical description of interface
      debonding, dependent on interface stress criteria, and soft tissue interface
      interposition, dependent on relative interface motions. Three simplified models
      of orthopaedic implants were constructed: a cortical bone screw for fracture
      fixation plates, a femoral resurfacing prosthesis and a straight stem model,
      cemented in a bone. The predicted computer configurations were compared with
      clinical observations. The computer results showed how interface disruption and
      fibrous tissue interposition interrelate and possibly enhance each other, whereby
      a progressive development of the soft tissue layer can occur. Around the cortical
      bone screw, the predicted resorption patterns were relatively large directly
      under the screw head and showed a pivot point in the opposite cortex. The
      resurfacing cup model predicted some fibrous tissue formation under the medial
      and lateral cup rim, whereby the medial layer developed first because of higher
      initial interface stresses. The straight stem model predicted initial interface
      failure at the proximal parts. After proximal resorption and fibrous tissue
      interposition, the medial interface was completely disrupted and developed an
      interface layer. The distal and mid lateral side maintained within the strength
      criterion. Although the applied models were relatively simple, the results showed
      reasonable qualitative agreement with resorption patterns found in clinical
      studies concerning bone screws and the resurfacing cup. The hypothesis that
      interface debonding and subsequent relative (micro)motions could be responsible
      for bone resorption and fibrous tissue propagation is thereby sustained by the
      results.

PMID- 8262990
TI  - Loading and deformation of the cat posterior knee joint capsule in axial and
      extension rotations.
AB  - Deformation and loading of the knee posterior joint capsule were studied in the
      cat, in extension rotations and in axial external (ER) and internal (IR)
      rotations at full extension. Loads were measured in the ligament along the upper
      edge of the capsule, using mechanically sensitive neurons that were calibrated as
      load cells. Strains were measured across the surface of the capsule, by tracking
      a set of markers attached to its surface. External rotations produced small loads
      in the cable: with applied moments of up to 0.25 Nm, cable tensions were less
      than 0.8 mPa. The cable was not loaded by internal rotations. Axial rotations
      produced predominantly shear strains in the capsule. Extension produced small
      loads in the ligament and the predominant capsule strain was tensile along the
      axis of the femur. These results show that the posterior capsule has a small role
      in resisting extension, a minimal role in providing axial stability in ER, and no
      such role in IR.

PMID- 8262991
TI  - A large-deformation, finite-element study of chondrodiatasis in the canine distal
      femoral epiphyseal plate.
AB  - A large-deformation, finite-element analysis was conducted to model stress fields
      around the developing growth plate as a first approach to comprehend the clinical
      application of traction for limb lengthening procedures. The model chosen was a
      cross section through the distal femoral growth plate of a 14-week-old dog. The
      chosen section passed through two of the conformational bends (mammillary
      processes) formed by the natural convolutions of the physis. Three different
      loading conditions were applied to the distal femoral epiphyseal model. The model
      also examined the effects of different values of Young's modulus of the growth
      plate cartilage. The cortical bone in all cases, experienced the highest
      stresses. In the growth plate, the highest principal stresses occurred where the
      physis intersects cortical bone. There were localized stresses that were higher
      than those that caused fracture in a rabbit model [Guse et al., J. Orthop. Res.
      7, 667-673 (1989)]. Results also indicated the following: a small tilt of 0.1
      degree in loading application increases the maximum principal stresses and the
      von Mises stresses in certain regions of the growth plate by about 8%; the
      shearing stresses in the growth plate are sensitive to Young's modulus of the
      growth plate; and traction pins that do not grip the cancellous bone in the
      epiphysis will increase the regions of high principal stress in the growth plate.

PMID- 8262992
TI  - Cross-sectional geometrical properties and bone mineral contents of the human
      radius and ulna.
AB  - The mechanical strength of the human radius and ulna depends on their geometrical
      and material properties. This study quantifies the cortical bone cross-sectional
      properties of the adult radius and ulna (cross-sectional area, thickness,
      centroids, area moments of inertia and section moduli) using computerized
      tomographic (CT) scanning coupled with image processing along the lengths of
      eight human cadaveric forearms. Bone mineral mass and apparent ash density were
      also quantified at serial locations. Sites of significant variation of selected
      geometric and mineral properties along the length of each forearm bone were
      determined. Our results show that interpolation of CT measurements made at 10 and
      30% of the radial length in the radius and 30 and 90% of the radial length in the
      ulna can provide approximate geometric values over the 10-90% region. This
      information can be used to develop a protocol using the fewest sites to
      clinically assess changes in forearm bone geometry. Regression analyses did not
      show significant linear relationships between geometric properties and apparent
      cortical ash density. Thus, CT derived geometric properties are not helpful in
      estimating the extent of changes in bone density. Area moment of inertia results
      suggest that the junction of the middle and distal third of the radius, and the
      ulnar shaft region may have increased vulnerability to fractures. The former is
      likely due to the change in moment of inertia values, whereas the latter is due
      to the relatively small magnitude of cross-sectional moments along the ulnar
      shaft as compared to the proximal or distal ends. This is consistent with
      fracture patterns observed clinically when a single forearm bone is fractured:
      Galeazzi fracture of the radius and nightstick fracture of the ulna.

PMID- 8262993
TI  - Indentation assessment of biphasic mechanical property deficits in size-dependent
      osteochondral defect repair.
AB  - The apparent biphasic material properties of 10-month osteochondral defect repair
      tissue were determined for a series of full thickness defects of 1, 3, or 5 mm
      diameter, created in weight-bearing regions of 48 canine femoral condyles. Load
      cell recordings from indentation tests were compared with resultant contact
      forces computed using a corresponding linear biphasic finite element model. The
      spread of cartilage engagement by a spherical ended indentor was modeled by
      successively imposing an impenetrability kinematic boundary condition at
      cartilage surface nodes for which incipient indentor surface penetration was
      detected. For each indentation test, a least-squares-error curve fitting
      procedure was used to identify a set of biphasic coefficients (aggregate modulus,
      permeability, Poisson ratio) that closely modeled experimental behavior. In the
      near neighborhood of best-fit, the finite element solutions were found to be much
      more sensitive to aggregate modulus perturbations than to permeability
      permutations, suggesting that perceived permeability increase may be of lesser
      value as a discriminant of repair tissue inadequacy. Compared to surrounding
      cartilage, the repair tissue for all defect sizes had statistically significant
      decreases in aggregate modulus and in Poisson ratio (much more so for 3 and 5 mm
      defects than for 1 mm defects). The two larger defect diameters had significant
      increases in permeability, whereas the 1 mm defects did not. While the material
      property deficits were consistent, substantial and comparable to those in other
      recent animal models of osteochondral defect repair, the size-dependence per se
      of the observed constitutive differences was only modest.

PMID- 8262994
TI  - Response of intersegmental knee loads to foot/pedal platform degrees of freedom
      in cycling.
AB  - The hypothesis tested in this article was that the three-dimensional
      intersegmental knee loads would be reduced in cycling by foot/pedal platforms
      which permitted relative motion between the foot and pedal. To test this
      hypothesis, pedal load and lower limb kinematic data were collected from 11
      subjects who pedaled with four foot/pedal platforms mounted on a six-load
      component dynamometer. One of the four platforms did not allow any relative
      foot/pedal movement while the other three permitted either medial/lateral
      translation, adduction/abduction rotation or inversion/eversion rotation. Three
      dimensional intersegmental knee loads were computed for each of the four
      platforms using a previously reported biomechanical model. A number of quantities
      describing each of the intersegmental knee load components was computed and
      compared using analysis of variance techniques. The key results were that the
      medial/lateral translation platform did not cause significant differences in
      intersegmental knee load quantities relative to those for the fixed platform.
      However, both of the platforms permitting rotations significantly reduced many
      but did not significantly increase any intersegmental knee load quantities. Of
      these two platforms, the abduction/abduction platform significantly reduced both
      the axial and varus/valgus knee moments while the inversion/eversion platform
      significantly reduced only varus/valgus moments. These results have application
      to bicycle pedal design where the goal is to reduce intersegmental knee loads,
      hence possibly alleviating overuse knee injuries.

PMID- 8262995
TI  - A constitutive relation for passive right-ventricular free wall myocardium.
AB  - We applied the pseudostrain energy function of Humphrey et al. [J. biomech. Engng
      112, 333-346 (1990a, b)] to characterize the passive biaxial mechanical
      properties of the right ventricle free wall myocardium [Sacks and Chuong, J.
      biomech. Engng 115, 202-205 (1993)]. The myocardium was assumed to be
      incompressible, pseudoelastic, and transversely isotropic, with transmural
      variations in fiber orientation within test specimens accounted for by the strain
      energy function. Using nonlinear regression, material constants were determined
      for the right ventricle free wall myocardium from the sinus and conus regions.
      The pseudostrain energy function was found to model the biaxial mechanical data
      well (r2 > 0.99). Transmural variations in Cauchy stresses, as well as the
      magnitude of the in-plane shear stress, were found to be small. Although
      comparisons with the left ventricle midwall myocardium data [Humphrey et al., J.
      biomech. Engng 112, 340-346 (1990b)] show clear quantitative differences, there
      is an overall qualitative similarity in the mechanical behavior of ventricular
      myocardium.

PMID- 8262996
TI  - An indirect method to assess wrist ligament forces with particular regard to the
      effect of preconditioning.
AB  - A method has been developed to calculate the forces that are developed in the
      ligaments of a joint specimen during motions. This indirect method is needed
      since direct measurements fail in the case of small ligaments. As an example the
      small ligaments of the carpal joint are considered. The rationale of the method
      is that the force generated in a ligament depends on the amount of strain to
      which it is subjected and on its material characteristics. In the method
      presented the lengths of the ligaments are determined in vitro at several joint
      positions by means of rontgenstereophotogrammetry. The zero-force length and the
      force-elongation relationship are determined on the same ligaments isolated in a
      materials testing machine. Over a considerable part of the strain range the
      measurement errors are relatively small compared to the forces determined, less
      than 10%. The method is applicable to joints in situations where other measuring
      methods cannot be used. The present analysis shows, however, that the force
      values determined are susceptible to preconditioning of the ligaments. In
      preconditioned ligaments the forces could be up to 50% lower than in the non
      preconditioned situation. This suggests that ligament forces may vary
      considerably in vivo, depending on the extent of preconditioning provoked by a
      particular function.

PMID- 8262997
TI  - Metal ion concentrations in retrieved polyethylene total hip inserts and
      implications for artifactually high readings in tissue.
AB  - Although there are many studies which document high metal ion concentrations in
      clinically retrieved tissues surrounding total joint replacements, most
      investigations have remained cautious in their interpretation due to the
      artifactual influences of metal particulate. The possible contribution of
      polyethylene wear debris to artifactually high periprosthetic metal ion
      concentration readings has not been previously considered. This study documents
      the potential role of polyethylene particulate contamination in causing
      artifactually high metal concentration readings in tissues. The data showed metal
      ion contamination in the polyethylene was progressive at each stage of exposure
      to metal: from bar stock preparation, to manufacturing, to in vivo ambulation.
      The manufacturing and machining processes showed a statistically significant (P <
      or = .05) increase in metal ion concentrations in the nonarticulated acetabular
      inserts over bar stock. The results of this study demonstrate that periprosthetic
      tissue and synovial fluid metal ion concentration data must be interpreted with
      caution due to possible artifactual problems associated with metal ion
      contaminated polyethylene particulate.

PMID- 8262998
TI  - Scanning electrochemical microscopy of metallic biomaterials: reaction rate and
      ion release imaging modes.
AB  - The Scanning Electrochemical Microscope (SECM) is a nonoptical scanning
      microscopic instrument capable of imaging highly localized electrical currents
      associated with charge transfer reactions on metallic biomaterials surfaces. The
      SECM operates as an aqueous electrochemical cell under bipotentiostatic control
      with a microelectrode and sample independently biased as working electrodes.
      Microelectrode current and position is recorded as it is scanned very near a
      metallurgically polished planar sample surface. To date, the SECM has imaged
      metallic biomaterials surfaces in oxygen reaction rate imaging (ORRI) and ion
      release and deposition imaging (IRDI) modes. In ORRI, sample and microelectrode
      are biased at sufficiently negative potentials to reduce absorbed oxygen. As the
      microelectrode scans areas of active oxygen reduction, localized diffusion fields
      with decreased oxygen solution concentrations are encountered and resultant
      decrements in microelectrode current are observed. In IRDI mode the sample is
      positively biased and the microelectrode is negatively biased. The microelectrode
      detects anodic dissolution products with highest currents being observed over the
      most active areas. Performance of the SECM has been evaluated on Ni minigrids,
      gamma-1 Hg-Ag dental amalgam crystals, and sintered beads of Co-Cr-Mo alloy which
      represent significantly different geometries and corrosion processes to help
      demonstrate the potential of this instrument. The SECM is a valuable tool for
      imaging microelectrochemical processes on the surfaces of metallurgically
      polished metallic biomaterials samples and a wide variety of other surfaces of
      biological interest where charge transfer reactions occur. The SECM allows
      selective biasing of metallic biomaterials surfaces and Faradaic reactions can be
      selectively imaged while the surface is in the active, passive, or transpassive
      state.

PMID- 8262999
TI  - Endothelial cell compatibility testing of three different Pellethanes.
AB  - There is a need for viable small diameter vascular grafts, the luminal surface of
      which could be seeded by endothelial cells (ECs) to prevent thrombosis. In order
      to select candidates for EC seeding before implantation, the in vitro
      cytocompatibility of three different Pellethanes (polyetherurethanes) using human
      ECs was investigated. The methodology included two stages depending on either
      direct contact between cells and materials or contact between cells and material
      extracts, obtained under standardized conditions. By the latter method, we
      observed a cytotoxic effect on cell growth with 2363-55 D Pellethane extract at a
      50% (v/v) concentration in the nutrient medium, likely provoked by leachables and
      correlated with the lowest levels of tPA, PAI1, and vWF antigens in the
      supernatants. By the former method, we studied EC attachment and growth.
      Morphology was studied by classical means and completed by scintigraphy and
      microautoradiography after 111Indium-labeling of the EC monolayer.
      Differentiation was determined by the release of vWF antigen and measurement of
      vWF activity (multimeric organization) after human thrombin stimulation. Despite
      an inhibition of proliferation for both 55 D and 75 D types (compared to the
      control), a functional monolayer of ECs was obtained on 75 D. Pellethane 75 D
      could be the best support for in vitro endothelization.

PMID- 8263000
TI  - Immobilization of poly(ethylene glycol) onto a poly(vinyl alcohol) hydrogel: 2.
      Evaluation of thrombogenicity.
AB  - Immobilized polyethylene glycol (PEG) reduced the amount of bovine serum albumin
      (BSA) adsorbed on polyvinyl alcohol (PVA) hydrogel, but did not reduce the
      platelet reactivity of the hydrogel surface. PEG, molecular weight (MW) 2000 or
      5000, with or without a monomethoxy end group, was covalently bound to
      glutaraldehyde-crosslinked PVA either through a cyclic acetal or an urethane
      functional group with a surface coverage of 70% (as measured by x-ray
      photoelectron spectroscopy [XPS]). Immobilization of monomethoxy-PEG via a cyclic
      acetal reduced BSA adsorption to PVA from 11 +/- 2 nmol/m2 to 3.9 +/- 0.3 nmol/m2
      and 3.3 +/- 0.3 nmol/m2 for MW 2000 and 5000, respectively. Similarly, urethane
      bound PEG reduced adsorption to 3.5 +/- 1.6 nmol/m2 for MW 2000 and 5.4 +/- 1.0
      nmol/m2 for MW 5000. Whole blood clotting times of PVA (using a Chandler loop)
      were not affected by covalently linked PEG, although the initial rate of thrombin
      generation at the surface, measured using a fluorogenic substrate, was marginally
      reduced; a rate constant of 4.2 +/- 0.1 cm/sec and 3.5 +/- 0.1 cm/sec were
      obtained for MW 2000 and 5000, respectively, compared to 5.6 +/- 1.0 cm/sec for
      PVA. Ex vivo evaluation using a canine arteriovenous shunt revealed that the
      hydrogel, with or without bound PEG, reduced circulating platelet levels by 35
      70% after 4 days. The initial fractional rate of platelet destruction determined
      from measurement of platelet cyclooxygenase activity, indicated that cyclic
      acetal or urethane bound PEG of either molecular weight had no effect on platelet
      consumption produced by PVA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263001
TI  - Biocompatibility of silicon-based electrode arrays implanted in feline cortical
      tissue.
AB  - The passive biocompatibility of silicon-based electrode arrays was studied in
      feline cortical tissue. Three types of arrays were used: uncoated, coated with
      polyimide, and coated with polyimide over an adhesion promoter. Fifteen arrays
      were implanted for 24 h to determine early tissue reaction to the implantation
      procedure, and twelve arrays were implanted for 6 months to determine structural
      and material biocompatibility. Edema and hemorrhage were present around the short
      term implants, but involved less than 6% of the total area of the tissue covered
      by the array. With chronic implants, leukocytes were rarely present and
      macrophages were found around roughly one-third of the tracks. Remnants of
      foreign material from the electrodes could be identified in less than 10% of the
      tracks. Gliosis was found around all tracks, forming an annulus between 20 and 40
      microns thick. A capsule was not always present, and never exceeded a thickness
      of 9 microns. These results suggest that the implantation procedure produces
      limited amounts of tissue damage, and that the arrays are biocompatible. However,
      the arrays insulated with polyimide over a primer had significantly greater
      involvement of macrophages, gliosis, and capsule formation than uncoated arrays
      and arrays insulated with polyimide without printer, perhaps indicating a
      reaction to aluminum oxide in the primer.

PMID- 8263002
TI  - Osteogenic differentiation of marrow stromal stem cells in porous hydroxyapatite
      ceramics.
AB  - Bioactive materials such as hydroxyapatite ceramics (HA) are known to show a
      stable interfacial bond with tissues (the bone bonding property has been
      especially well documented). However, the biological phenomenon on the material
      surface that evoke bone bonding is not well documented. To address this issue,
      composites of porous HA and rat marrow cells were implanted into ectopic
      (subcutaneous) sites. At 3 weeks after implantation, active osteoblasts lining
      the HA surface initiated bone formation, primarily as mature bone (lamellar
      type). Gene expression study using Northern blot analysis of the composites
      showed that alkaline phosphatase (ALP) and bone Gla protein (BGP) mRNAs began to
      appear at 2 weeks and the level of BGP mRNA at 4 weeks was comparable to that of
      cancerous bone. However, HA implantation without marrow cells did not show bone
      formation and neither BGP nor ALP mRNA were detected. These results indicate that
      the HA surface is able to support cell differentiation (osteoblastic phenotype
      expression of marrow stromal stem cells), as well as cell coordination resulting
      in mature bone formation that bonds to the HA.

PMID- 8263003
TI  - Mechanisms of polymer degradation in implantable devices. 2. Poly(DL-lactic
      acid).
AB  - The hydrolytic degradation of poly(DL-lactic acid) in an aqueous environment in
      which hydroxyl radicals have been generated has been investigated. Different
      methods (gel permeation chromatography, differential scanning calorimetry, and
      scanning electron microscopy) were employed to study the mechanisms of
      degradation of this amorphous physiologically absorbable polymer. The data
      indicated that the hydroxyl radical is likely to be a significant factor in the
      degradation of this polymer.

PMID- 8263004
TI  - Difference in bone ingrowth after one versus two daily episodes of micromotion:
      experiments with titanium chambers in rabbits.
AB  - Mechanical stimulation has been shown to affect the differentiation and
      development of mesenchymal tissue. In the present study, we compared the
      histological and histomorphometric results of tissue ingrowth into micromotion
      chambers that were moved at 0 cycles per day, 20 cycles once per day, and 20
      cycles twice per day over 20-30 sec, for 3 weeks. In each case, a chamber having
      a 1 x 1 x 5 mm square-holed groove for tissue ingrowth was used. The total
      amplitude of motion was 0.75 mm. Histological sections from nonmoved chambers
      contained extensive trabecular bone, embedded in a fibrovascular stroma.
      Histomorphometric analysis disclosed that bone comprised a mean of 31 +/- 2%
      (mean +/- SEM) of the ingrown tissue. Twenty movements per day appeared to
      further stimulate bone ingrowth (46 +/- 5%). Extensive ingrowth of more immature
      woven and trabecular bone was noted in a more cellular stroma. In general,
      increasing the degree of micromotion to 20 movements twice per day resulted in a
      decreased amount of bone formation (19 +/- 7%). In several of these specimens,
      little or no bone could be found. These experiments have demonstrated that, for
      the parameters chosen in this study, a short daily period of low frequency,
      micromotion may facilitate bone ingrowth; however, when the same motion is
      delivered twice daily, bone ingrowth is depressed. Thus a "window" of externally
      applied strain appears to exist, which may facilitate or discourage tissue
      differentiation to bone.

PMID- 8263005
TI  - Effect of a combined gamma irradiation and Parylene plasma treatment on the
      hydrolytic degradation of synthetic biodegradable sutures.
AB  - The aim of this study was to alter the hydrolytic degradation property of
      synthetic absorbable suture fibers so that their mass loss would occur at a
      shorter time without significantly compromising their tensile strength loss
      profile. A two-step treatment concept (gamma-irradiation followed by Parylene
      plasma deposition) was introduced for achieving this aim. Vicryl and Maxon were
      used as the model compounds to test this new concept. After the treatment, the in
      vitro hydrolytic degradation properties of Vicryl and Maxon were evaluated by
      weight loss, tensile breaking strength, heat of fusion and melting temperature,
      intrinsic viscosity, surface wettability, and surface morphology. The results
      suggested that gamma-irradiation at a dosage level between 0.2-2.0 Mrad for
      Vicryl sutures and about 2.0 Mrad for Maxon sutures were the most effective
      dosages to accelerate the suture mass loss. The subsequent Parylene plasma
      deposition treatment statistically significantly improved the retention of
      tensile strength for both gamma-irradiated Vicryl and Maxon sutures and hence
      counteracted the undesirable gamma-irradiation induced acceleration of tensile
      strength loss. However, this second-step Parylene plasma treatment extended the
      suture mass loss to longer periods. These findings were consistent with the
      observed surface wettability, surface morphology, intrinsic viscosity, and
      thermal properties. A thin hydrophobic Parylene skin layer wrapped around a
      suture was responsible for the slower rate in mass and strength loss. This outer
      skin layer acted as a barrier to not only water but also degradation fragments.

PMID- 8263006
TI  - Effect of polyol type on the physical properties and thrombogenicity of sulfonate
      containing polyurethanes.
AB  - Polyetherurethanes (PEUs) based on polytetramethylene oxide (PTMO) as the polyol,
      and derivatized with propyl sulfonate functionality, have previously been shown
      to possess antithrombotic properties. In this article, the bulk physical
      properties of sulfonated and nonsulfonated polyurethanes containing either
      polyethylene oxide (PEO) or PTMO as the soft segment are studied. The in vitro
      shape-change of platelets in contact with these surfaces, and their ex vivo blood
      contacting response are also investigated. It was found that PEO-base was
      physically weaker than PTMO-base, which is attributed to a lower degree or phase
      separation in the former. In the dry state, sulfonation enhanced the physical
      properties for PTMO-containing polyurethane (PTMO-SO3-0.20), but weakened the PEO
      containing polyurethane (PEO-SO3-0.15). In vitro platelet spreading studies
      showed the lowest degree of platelet spreading and also the lowest platelet
      density on PEO-base, while platelet spreading and density on the other three
      materials and polyethylene (PE) was greater. The thromboresistance of these
      materials was evaluated using a canine arteriovenous series shunt ex vivo. It was
      determined that PTMO-SO3-0.20 was the least thrombogenic, followed by both PEO
      base and PEO-SO3-0.15, and that PTMO-base was the most thrombogenic.

PMID- 8263007
TI  - Radioimmunotherapy: no news from the newcomer.

PMID- 8263008
TI  - Promoting effects of ethinyl estradiol on development of renal proliferative
      lesions induced by N-nitrosobis (2-oxopropyl)amine in female Syrian golden
      hamsters.
AB  - The modulating effects of female sex hormones, ethinylestradiol and
      levonorgestrel, on the development of renal proliferative lesions after
      initiation with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Three
      groups of female Syrian golden hamsters, each comprising 30 animals, were given
      four weekly s.c. injections of BOP (10 mg/kg body weight) and then fed diet
      containing 1 ppm ethinylestradiol (group 1: BOP/EE), diet containing 10 ppm
      levonorgestrel (group 2) or basal diet (group 3) for the next 27 weeks. As
      hormone controls, two groups of 20 female hamsters each received diet containing
      1 ppm ethynylestradiol (group 4) and 10 ppm levonorgestrel (group 5) from week 3
      for 27 weeks without the prior initiation treatment. The severity of diffuse
      anisokarya, characterized by varied nuclear size and the incidence of dysplasias
      of the proximal tubular epithelia induced by BOP, were significantly increased in
      the BOP/EE group, indicating the promoting effects of the hormone. In the renal
      dysplastic lesions (small-cluster, cystic, clear-cell and acidophilic cell
      types), adenomas and nephroblastomas, increases in the numbers of argyrophilic
      proteins associated with nucleolar organizer regions (NOR) in the nucleus,
      suggesting a high proliferative activity, were seen in dysplasia of acidophilic
      cell types and adenomas. In addition, the number of bizarre NOR per nucleus was
      significantly higher in adenomas than in dysplasias and highest in
      nephroblastomas. This morphological change in NOR should therefore be a useful
      parameter for the diagnosis of malignancy of renal tumors.

PMID- 8263009
TI  - Gene analysis of K-, H-ras, p53, and retinoblastoma susceptibility genes in human
      lung cancer cell lines by the polymerase chain reaction/single-strand
      conformation polymorphism method.
AB  - In order to know the involvement of multiple gene alterations in the pathogenesis
      of human lung cancer, we examined the genes of K-, H-ras (codons 12, 13, 61),
      p53(exons 5-9) and the retinoblastoma susceptibility gene (RB)(exons 20-22) using
      the polymerase chain reaction/single-strand conformation polymorphism method in
      32 human lung cancer cell lines (5 squamous-cell carcinomas, 10 adenocarcinomas,
      3 large-cell carcinomas, 14 small-cell carcinomas). In 18 non-small-cell lung
      cancer lines, gene alterations were found in 4 for K-ras (22%), none for H-ras
      (0%), 4 for p53 (22%) and none for the RB (0%) gene. In 14 small-cell lung cancer
      (SCLC) lines, no gene alterations were found in K-ras (0%), or H-ras (0%), but 6
      were found for p53 (43%) and 3 for the RB (21%) gene. Coincident abnormalities of
      K-ras and p53, or K-ras and RB genes were not found in any cell lines, and those
      of the p53 and RB genes were found in only 2 SCLC lines. No association was
      observed between these three gene alterations and N-myc amplification. Although
      the above three genes may be involved to some extent in the pathogenesis of lung
      cancer, more factors are required for its development.

PMID- 8263010
TI  - Culture of retinoblastoma cells from clinical specimens: growth-promoting effect
      of 2-mercaptoethanol.
AB  - Establishment of new tumor cell lines is an important first step for biological
      studies of tumor cells. High success rates in establishing retinoblastoma cell
      lines have been reported when feeder-layer culture but not liquid-culture
      techniques were used. Liquid culture is, however, essential for studies in which
      feeder-layer cells are undesirable. In a previous study, we formulated a medium
      (RB-- medium), the components of which were almost identical to those of a soft
      agar medium developed for colony formation of established retinoblastoma cell
      lines, in which one cell line from 12 primary retinoblastoma specimens was
      established. In this study, another medium (RB++ medium), RB-- medium to which 20
      microM 2-mercaptoethanol and 375 microM asparagine were added, was tested for its
      ability to grow retinoblastoma cells from clinical specimens. In the RB++ medium,
      6 cell lines from 16 primary sites, 2 from 2 intraocular-recurrent and 3 from 3
      metastatic retinoblastomas grew for over a year. The major reason for the
      apparent improvement of the RB++ medium on the RB-- medium was demonstrated to be
      the addition of 2-mercaptoethanol.

PMID- 8263011
TI  - The effect of phorbol ester treatment on migration of C3H 10T1/2 and BT5C glioma
      cells: possible application to carcinogenesis.
AB  - Treatment with the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol 13
      acetate (TPA) and the second-stage promoter 12-O-retinoylphorbol 13-acetate
      induced down-regulation of protein kinase C (PKC) and enhanced the migration of
      C3H 10T1/2 cells. In the case of BT5C glioma cells the same negative correlation
      was observed only after treatment with TPA. The negative control 4 alpha-phorbol
      affected neither PKC activity nor the migratory ability of both cell lines.

PMID- 8263012
TI  - Gastric carcinogenesis in rats given hypertonic salt at different times before a
      single dose of N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - A 1-ml dose of 4.5 M NaCl was given intragastrically to male Wistar rats at 10
      min, 1 h, 4 h, 12 h, 24 h or 48 h before a single intragastric dose of 250 mg/kg
      N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). After 52 weeks the incidence of
      forestomach squamous cell carcinoma was 21% in control animals receiving MNNG
      alone. The cancer incidence in the forestomach varied with the time elapsed
      between application of NaCl and MNNG, and was significantly increased in animals
      pretreated with NaCl 4 h (43%), 12 h (54%) and 24 h (41%) before MNNG. These
      results show that salt has a cocarcinogenic effect on initiation of forestomach
      carcinogenesis in rats, and that this effect depends on the time interval between
      pretreatment with NaCl and application of MNNG. Gastric adenocarcinomas occurred
      more frequently in the antrum (78%) than in the corpus (22%). The incidence of
      gastric adenocarcinoma in animals pretreated with salt before application of MNNG
      (11%-22%) was not significantly influenced by the time elapsed between
      pretreatment with salt and application of MNNG, and did not differ from animals
      receiving MNNG alone (18%). The lack of a cocarcinogenic effect of NaCl on
      glandular gastric carcinogenesis might be due to the use of dimethyl/sulfoxide as
      solvent for MNNG.

PMID- 8263013
TI  - Intravascular lymphomatosis: a clinicopathological study of three cases.
AB  - In patients with intravascular lymphomatosis (IL) a broad spectrum of neuro
      psychiatric disorders including dementia, focal neurological signs and seizures
      has been reported. Clinical diagnosis is difficult since neuroimaging findings
      are nonspecific. The clinical histories, biopsy and autopsy findings of three
      patients with IL, one with brain biopsy, are described. Two of them presented
      with rapidly progressive, fluctuating dementia. The third patient suffered from
      seizures followed by aphasia. Histology revealed large-cell lymphoma of the B
      cell type. The prognosis of IL, in general, is poor.

PMID- 8263014
TI  - A phase I trial of intrapleural recombinant human interferon alpha (rHuIFN alpha
      2b) in patients with malignant pleural effusions.
AB  - The use of intrapleural sclerosing agents to control reaccumulation of pleural
      fluid in patients with malignant effusions has been widely investigated. A phase
      I trial of intrapleural recombinant human interferon alpha (rHuIFN alpha 2b) was
      initiated to determine the toxicity and maximal tolerated dose in this group of
      patients. rHuIFN alpha 2b was instilled as a single dose following chest tube
      (15/16) or percutaneous (1/16) drainage of cytologically proven malignant
      effusions. Doses of rHuIFN alpha 2b were escalated from 25 x 10(6) to 200 x 10(6)
      U/m2 in cohorts of three to four patients. Toxicity was mild to moderate, and
      included chills, fever and chest pain, and resembled that produced by systemic
      administration of rHuIFN alpha 2b. Dose-limiting toxicity occurred at 200 x 10(6)
      U/m2 and consisted of hepatic enzyme elevations and renal failure. Partial
      control of the effusions was noted in two patients, with two additional patients
      having stable disease. Phase II trials of rHuIFN alpha 2b should utilize up to
      150 x 10(6) U/m2 for intrapleural instillation.

PMID- 8263015
TI  - Phase II study of pirarubicin combined with cisplatin in recurrent ovarian
      cancer.
AB  - Although 50%-80% of patients with advanced ovarian cancer demonstrate an
      objective response after platinum-based chemotherapy, a majority of these
      patients will ultimately experience a relapse of their disease. Effective second
      line treatment for these patients is of the most importance. We performed a phase
      II study with cisplatin and pirarubicin (each drug 50 mg/m2 i.v. every 28 days)
      in 17 patients with relapsed or persistent ovarian carcinoma. All patients had
      received platinum-containing primary chemotherapy. Overall survival from the time
      of diagnosis was 38.3 months (45.3 months in relapsed ovarian carcinoma and 28.3
      months in ovarian carcinoma persisting after primary chemotherapy). Survival from
      entrance into the study was 13.0 months (14.2 months in relapsed disease and 11.2
      months in refractory disease). Time to progression was 10.3 months. An objective
      response was observed in 4 patients and another 3 patients had stable disease.
      Major toxicity consisted of emesis (grade III/IV in 60/64 courses) and
      myelosuppression WHO grade III/IV in 15 courses. Neurotoxicity occurred in 3
      patients and nephrotoxicity in 1 patient. Alopecia occurred in 12 patients.
      Tachycardia and other low-grade heart toxicities were observed after 5 courses.
      Dose reduction was necessary because of severe myelosuppression in 4 courses and
      because of nephrotoxicity in 1 course. Delay of subsequent chemotherapy courses
      for more than 7 days was necessary after 13 courses and was always due to
      myelosuppression. The dose-limiting toxicity of combination chemotherapy with
      cisplatin and pirarubicin is myelosuppression. Response and survival rates are
      superior in patients with relapsed disease compared to patients with resistant
      ovarian carcinoma.

PMID- 8263016
TI  - 7th International Symposium of the Division of Experimental Cancer Research (AEK)
      of the German Cancer Society. 24-26 March, 1993, Heidelberg, Germany.

PMID- 8263017
TI  - Gp80 (clusterin; TRPM-2) mRNA level is enhanced in human renal clear cell
      carcinomas.
AB  - The gp80 glycoprotein complex (clusterin, apolipoprotein J, TRPM-2) is a widely
      expressed protein that has been attributed functions in tissue remodelling,
      immune defense and transport of lipids and biologically active peptides. The
      expression of the protein appears to be elevated in several neurodegenerative,
      apoptotic and malignant processes. We show here that in patients with renal clear
      cell carcinoma gp80 mRNA is 3-fold overexpressed in tissue of the tumors compared
      with adjacent non-tumor tissue.

PMID- 8263018
TI  - Abnormalities of phosphoprotein gene expression in three osteopetrotic rat
      mutations: elevated mRNA transcripts, protein synthesis, and accumulation in bone
      of mutant animals.
AB  - Osteoclast abnormalities that characterize osteopetrosis, a disorder of bone
      resorption, may derive from aberrant signals from the osteoblast or the bone
      matrix. In the present studies, both synthesis and the bone matrix content of the
      major bone phosphoprotein component, osteopontin, were found to be elevated in
      three osteopetrotic rat mutations (ia, op, and tl). In whole bone, a twofold
      increase in the content of the characteristic amino acid O-phosphoserine for
      osteopontin occurred in op and tl mutant long bone, but a smaller (15%) and more
      variable increase was observed in ia mutant rat long bone. Extraction of the bone
      matrix components and partial purification by reverse phase chromatography showed
      a twofold increase in a phosphoprotein fraction relative to other noncollagenous
      components. Amino acid analysis and staining characteristics of SDS-PAGE
      fractionated proteins indicated this to be osteopontin. Organ cultures of
      calvarial bone from 4 day ia osteopetrotic mutant and normal rats in the presence
      of 3H-proline showed increased synthesis of this 60 kD protein, which was
      stimulated by vitamin D. Preparation of total cellular RNA from bone of 2- and 6
      week-old mutants and normal rats supported increased synthesis of osteopontin as
      reflected by hybridization with osteopontin cDNA probe, showing significantly
      higher levels of mRNA transcripts in ia (3-5 fold), tl (1.4-2 fold), and op (6-25
      fold) mutant bone compared to normal littermates. The changes in osteopontin mRNA
      levels in mutant bone were also examined in relation to other growth and
      phenotype-expressed genes. The findings of increased accumulation of osteopontin
      in osteopetrotic bone and increased synthesis by osteoblasts are interesting in
      light of the previously reported decrease in bone osteocalcin content
      (Endocrinology, 126:966, 1990), confirmed here by decreased osteocalcin mRNA
      transcripts. Such aberrations in the composition of skeletal extracellular matrix
      could be a reflection of or a contributing factor to the osteoclast abnormalities
      of some of these osteopetrotic disorders.

PMID- 8263019
TI  - Bumetanide and furosemide inhibited vascular endothelial cell proliferation.
AB  - In this study, we examined the role of the bumetanide-sensitive Na+/K+/Cl
      cotransport in the mitogenic signal of vascular endothelial cell proliferation.
      The activity of the Na+/K+/Cl- cotransport is dramatically decreased in quiescent
      subconfluent cells, as compared to subconfluent cells growing in the presence of
      FGF. The Na+/K+/Cl- cotransport activity of quiescent subconfluent cultures
      deprived of FGF decreased to 6%, whereas that of quiescent cells grown to
      confluency was reduced to only 33% of the activity of subconfluent cells growing
      in the presence of FGF. The basal low activity of Na+/K+/Cl- cotransport in the
      quiescent subconfluent vascular endothelial cells was dramatically stimulated by
      FGF. In order to explore the role of the Na+/K+/Cl- cotransport in the mitogenic
      signal of the endothelial cells, the effect of two specific inhibitors of the
      cotransport -furosemide and -bumetanide was tested on cell proliferation induced
      by FGF. Bumetanide and furosemide inhibited synchronized cell proliferation
      measured by direct counting of cells and by DNA synthesis. Inhibition by
      furosemide and bumetanide was reversible; removal of these compounds completely
      released the cells to proliferate. These results indicate that the effect of
      these drugs is specific and is not due to an indirect toxic effect. This study
      clearly demonstrates that the FGF-induced activation of the Na+/K+/Cl-
      cotransport plays a role in the mitogenic signal pathway of vascular endothelial
      cells.

PMID- 8263020
TI  - Increased ambient pressure stimulates proliferation and morphologic changes in
      cultured endothelial cells.
AB  - Very little is known about the effects of pressure within the vascular system on
      EC phenotype. To study this, bovine aortic EC were seeded on rat type I collagen
      plates (2,000/cm2) and allowed to attach for 24 hours. The cells were exposed to
      either atmospheric, 40, 80, or 120 mm Hg pressure by placing them in a plexiglass
      pressure chamber loaded with 5% CO2/air and maintained at 37 degrees C inside an
      incubator. Chamber pressure was continuously monitored with an amplified voltage
      transducer connected to a digital monitor. EC were maintained in DMEM
      supplemented with 10% calf serum and substrates for up to 9 days. The results
      indicate that EC proliferation is influenced by their ambient pressure. EC
      subjected in vitro to pressures comparable to mean systemic blood pressures had a
      significant increase in cell number compared to EC exposed to atmospheric
      pressures. EC were elongated and appeared to align randomly. We hypothesize that
      the systemic pressure which the endothelium is exposed to in vivo may have a
      significant regulatory influence on the ability of the endothelium to proliferate
      which may affect the endothelial cell response to injury.

PMID- 8263021
TI  - Actions of platelet-derived growth factor isoforms in mesangial cells.
AB  - Platelet-derived growth factor (PDGF) occurs as homodimers or heterodimers of
      related polypeptide chains PDGF-BB, -AA, and -AB. There are two receptors that
      bind PDGF, termed alpha and beta. The beta receptor recognizes PDGF B chain and
      is dimerized in response to PDGF BB. The alpha receptor recognizes PDGF B as well
      as A chains and can be dimerized by the three dimeric forms of PDGF AA, AB, and
      BB. To characterize PDGF receptor signaling mechanisms and biologic activities in
      human mesangial cells (MC), we explored the effects of the three PDGF isoforms on
      DNA synthesis, phospholipase C activation, and PDGF protooncogene induction. PDGF
      BB homodimer and AB heterodimer induced a marked increase in DNA synthesis,
      activation of phospholipase C, and autoinduction of PDGF A and B chain mRNAs,
      whereas PDGF-AA homodimer was without effect. The lack of response to PDGF AA
      could be accounted for by down-regulation of the PDGF-alpha receptor since
      preincubation of MC with suramin restored PDGF AA-induced DNA synthesis. Ligand
      binding studies demonstrate specific binding of labeled PDGF BB and AB and to a
      lower extent PDGF AA isoforms to mesangial cells. These results are consistent
      with predominant expression of PDGF beta receptor in MC, which is linked to
      phospholipase-C activation. The potent biologic effects of PDGF-AB heterodimer in
      cells that express very few alpha receptors and do not respond to PDGF AA are
      somewhat inconsistent with the currently accepted model of PDGF receptor
      interaction and suggest the presence of additional mechanisms for PDGF isoform
      binding and activation.

PMID- 8263022
TI  - TGF-beta 1 induces the expression of type I collagen and SPARC, and enhances
      contraction of collagen gels, by fibroblasts from young and aged donors.
AB  - Fibroblasts have a major role in the synthesis and reorganization of
      extracellular matrix that occur during wound repair. An impaired biosynthetic or
      functional response of these cells to stimulation by growth factors might
      contribute to the delayed wound healing noted in aging. We, therefore, compared
      the responses of dermal fibroblasts from young and elderly individuals (26, 29,
      65, 89, 90, and 92 years of age) to transforming growth factor-beta 1 (TGF-beta
      1) with respect to: (1) the synthesis of type I collagen and SPARC (two
      extracellular matrix proteins that are highly expressed by dermal fibroblasts
      during the remodeling phase of wound repair) and (2) the contraction of collagen
      gels, and in vitro assay of wound contraction. With the exception of one young
      donor, all cultures exposed for 44 hours to 10 ng/ml TGF-beta 1 exhibited a 1.6-
      to 5.5-fold increase in the levels of secreted type I collagen and SPARC,
      relative to untreated cultures, and exhibited a 2.0- to 6.2-fold increase in the
      amounts of the corresponding mRNAs. Moreover, the dose-response to TGF-beta 1
      (0.1-10 ng/ml), as determined by synthesis of type I collagen and SPARC mRNA, was
      as vigorous in cells from aged donors as in cells from a young donor. In assays
      of collagen gel contraction, fibroblasts from all donors were stimulated to a
      similar degree by 10 ng/ml TGF-beta 1. In conclusion, cells from both young and
      aged donors exhibited similar biosynthetic and contractile properties with
      exposure to TGF-beta 1. It therefore appears that the impaired wound healing
      noted in the aged does not result from a failure of their dermal fibroblasts to
      respond to this cytokine.

PMID- 8263023
TI  - Iron absorption by CaCo 2 cells cultivated in serum-free medium as in vitro model
      of the human intestinal epithelial barrier.
AB  - A cell culture system consisting of confluent monolayer of human enterocyte-like
      CaCo 2 cells, cultivated in a serum-free nutritive medium, on microporous
      synthetic membranes has been used as an in vitro model of the intestinal
      epithelial barrier. The uptake of 55ferric citrate, as well as the
      transepithelial passage from the apical to the basolateral pole, have been
      studied. CaCo 2 cells accumulate iron in a time- and concentration-dependent
      process, largely specific from the apical pole. When 55ferric citrate is added at
      the apical pole, radioiron appears at the basal pole and the clearance rate is
      approximately four times higher than in the opposite direction; the amounts of
      55Fe increase with the concentration in iron citrate and the duration of
      incubation. At least two concurrent mechanisms could be involved in iron
      absorption across monolayers of CaCo 2 cells. A first route would correspond to a
      paracellular passage of the metal from the apical to the basal pole. The second
      route would involve a selective intake of iron at the apical pole and could
      require a reduction of ferric iron, prior to the entry. Iron accumulated by the
      cells would, for a minor part, be stored within ferritin, whereas the major part
      would be excreted at the basolateral pole, either as low molecular weight
      material of undetermined chemical composition but from which iron is easily
      mobilized by apotransferrin or associated with neosynthesized apotransferrin.
      Vesicular transport and protein synthesis seem to be required.

PMID- 8263024
TI  - 31P NMR characterization of cellular metabolism during dexamethasone induced
      apoptosis in human leukemic cell lines.
AB  - 31P NMR has been used to study the effects of dexamethasone on phosphorus
      metabolism in one dexamethasone (dex)-sensitive (CEM-C7) and three different dex
      resistant (CEM-C1, CEM-4R4, and CEM-ICR27) human leukemic cell lines. The use of
      these cell lines, containing widely varying amounts of glucocorticoid receptors,
      made it possible to evaluate the receptor-mediated contributions to the modes of
      action of dexamethasone in these cells. To evaluate the effects of dexamethasone
      without any significant contribution from experimental conditions, all the
      experiments were done with parallel controls. Results obtained showed: 1)
      significantly different levels of phosphorylethanolamine (PE) and
      phosphorylcholine (PC) among cell lines, suggesting significant differences in
      phospholipid metabolism; 2) the dexamethasone induced reduction of
      phosphomonoester (PE+PC), ATP, and metabolic rates probably through
      glucocorticoid receptor mediated mechanisms; 3) the dexamethasone induced
      stimulation of cellular metabolism in a process which seems to be independent of
      glucocorticoid receptors; and 4) the dexamethasone induced alkaline shift of
      intracellular pH in all the cell lines except ICR27. The reduction in PME levels
      seems to be an earlier step in dexamethasone-induced apoptosis than the reduction
      in ATP. The degree of alkaline shift was found to correlate with the number of
      glucocorticoid receptors present. The possible involvement of phospholipid
      metabolites as second messengers in dexamethasone-induced apoptosis is discussed.

PMID- 8263025
TI  - Synthesis, degradation, and subcellular localization of proteins encoded by the
      primary response genes TIS7/PC4 and TIS21/PC3.
AB  - Murine TIS7 and TIS21 cDNAs were cloned from phorbol ester-induced Swiss 3T3
      cells. The cognate rat cDNAs, PC4 and PC3, were cloned from nerve growth factor
      (NGF)-treated PC12 pheochromocytoma cells. The TIS7/PC4 and TIS21/PC3 primary
      response genes are rapidly and transiently induced in response to serum, phorbol
      esters, and polypeptide growth factors in quiescent Swiss 3T3 cells and by NGF
      and other ligands in PC12 cells. In both 3T3 and PC12 cells the appearance of the
      TIS21/PC3 message precedes that of TIS7/PC4 message following ligand stimulation,
      suggesting that the TIS21/PC3 protein is likely to be synthesized more rapidly
      than the TIS7/PC4 protein. Using antisera prepared against recombinant TIS21 and
      TIS7 proteins, we find that the TIS21/PC3 protein is, indeed, synthesized more
      rapidly than the TIS7/PC4 protein following stimulation in both 3T3 and PC12
      cells. In addition, "pulse-chase" experiments demonstrate that the TIS21/PC3
      protein is degraded much more rapidly than the TIS7/PC4 protein. The sequences of
      the predicted PC3 and PC4 proteins have lead to the speculation that these two
      proteins may both be secreted from cells following stimulation. The PC4 protein
      is reported to have some sequence similarity to interferons. The TIS21/PC3
      protein contains a presumptive leader sequence. Using our antisera to the
      recombinant proteins, however, we cannot detect secretion of radiolabelled
      TIS7/PC4 or TIS21/PC3 protein. Immunohistochemical and subcellular fractionation
      experiments suggest that the TIS7 protein is a membrane associated, non-nuclear
      intracellular protein. The TIS21 protein, in contrast, is a non-nuclear, soluble
      intracellular protein.

PMID- 8263026
TI  - Slowed receptor trafficking in mutant CHO lines of the End1 and End2
      complementation groups.
AB  - A mutant Chinese hamster ovary cell line with nonconditional kinetic defects in
      receptor internalization and recycling was isolated, based on selection for
      resistance to a transferrin-diphtheria toxin conjugate and screening for aberrant
      receptor trafficking. The 12-4 cell line internalizes transferrin at
      approximately 75% of the parental rate and recycles transferrin back to the cell
      surface at approximately 55% of the parental rate. Internalization of low density
      lipoprotein is also reduced to approximately 70% of the parental cell rate,
      demonstrating that the mutant phenotype affects the trafficking of multiple
      receptors. Characterization of somatic cell hybrids indicated that the 12-4
      phenotype is recessive, and complementation analysis determined that the 12-4
      cell line is a member of the End2 complementation group. End2 mutants have
      previously been described as defective in endosomal acidification but have not
      been known to be defective in receptor trafficking. We have found similar defects
      in another End2 mutant cell line, suggesting that slowed receptor trafficking is
      characteristic of End2 mutants. Interestingly, transferrin receptor recycling and
      internalization are also slowed in another complementation group of mutants,
      End1, that is also defective in endosomal acidification. This study demonstrates
      altered receptor trafficking in End1 and End2 cell lines, a novel aspect of the
      mutant phenotypes. These findings provide evidence, based on a cellular genetic
      approach, that proper endosome acidification is necessary for maintenance of
      normal receptor recycling.

PMID- 8263027
TI  - Response of stratified cultures of human keratinocytes to disruption of
      proteoglycan synthesis by p-nitrophenyl-beta-D-xylopyranoside.
AB  - Proteoglycans play a role in regulating proliferation and adhesion of cells to
      each other and to the basal lamina. Synthesis of proteoglycans is disrupted by
      beta-xylosides, which serve as alternate substrate sites for glycosaminoglycan
      chain attachment and therefore prevent glycosylation of the core protein. We have
      investigated the effects of p-nitrophenyl-beta-D-xylopyranoside (PNP-xyloside) on
      cultured human keratinocytes. Stratified cultures were incubated for 7 days with
      PNP-xyloside (0.05-2.0 mM). Concentrations as low as 0.05 mM increased the
      secretion of free chondroitin sulfate by 10-15-fold over untreated cultures. Cell
      associated proteoglycan decreased as PNP-xyloside concentration increased. At 2
      mM PNP-xyloside, heparan sulfate as well as chondroitin sulfate addition to core
      proteins was disrupted: the core protein of epican, a heparan sulfate form of
      CD44 found on keratinocytes, was detected immunologically but lacked heparan
      sulfate. 2.0 mM PNP-xyloside reduced the number of attached cells by 20-25% after
      7 days, but had little effect on morphology or protein synthesis. These results
      indicate that intact proteoglycans are not critical for maintaining epidermal
      keratinocyte stratification, cell-cell adhesion, or growth.

PMID- 8263028
TI  - Injuries to cultivated BJA-B cells by ajoene, a garlic-derived natural compound:
      cell viability, glutathione metabolism, and pools of acidic amino acids.
AB  - Ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide), a garlic-derived natural
      compound, which had been shown to have cytostatic/cytotoxic properties, was
      tested with a B cell lymphoma-derived cell line (BJA-B cells) in order to
      elucidate its mechanism of cytotoxic action. Viability of the cells was
      determined by the Trypan blue exclusion test and the colorimetric tetrazolium
      (MTT) assay, whereas metabolic disturbance was evaluated by measuring the pools
      of reduced (GSH), oxidized glutathione (GSSG) and the acidic amino acids, Glu and
      Asp. Fast uptake of ajoene was accompanied by an immediate reduction of the GSH
      and increase in the GSSG levels. The extent of these changes, as well as the
      further development of the metabolite pools, depended on the ajoene dose per
      cell. At a sublethal ajoene dose the GSH and GSSG pools rose at the later stages
      to levels much higher than in the control experiment. Bleb formation at the
      cytoplasmic membrane was a further rapid phenomenon, although injuries detected
      by Trypan blue exclusion developed only at a later stage. The MTT assay,
      performed in a parallel experiment (48 h after ajoene addition), showed, however,
      that reduction of cell viability was established at the very beginning of ajoene
      exposure. Altogether, the action of ajoene strongly resembled oxidative stress
      (i.e., interference with SH homeostasis and its pleiotropic consequences to cell
      physiology and metabolism.

PMID- 8263029
TI  - Transrepression of type II collagen by TGF-beta and FGF is protein kinase C
      dependent and is mediated through regulatory sequences in the promoter and first
      intron.
AB  - Transforming growth factor beta and basic fibroblast growth factor are
      multipotential factors found in bone and cartilage that may be involved in both
      the proliferation and differentiation of chondrocytes. It was previously reported
      that TGF-beta plus FGF caused a modulation of chondrocyte phenotype that included
      the down-regulation of steady-state level of the collagen II transcript. In this
      report, the results of nuclear run-off data indicate that repression of
      transcript initiation from the collagen II gene is the primary mechanism involved
      in the growth factor induced inhibition. Transient transfection assays with CAT
      expression vectors containing portions of the collagen II gene show that the TGF
      beta/FGF induced transrepression requires a region in the first intron previously
      reported to have transcriptional enhancer activity and to bind chondrocyte
      nuclear proteins. In addition, silencer elements in the promoter also appear to
      play a role. Protein data as well as transient transfection experiments indicate
      that the activation of protein kinase C is necessary for the growth factor
      induced down-regulation of collagen II expression. These studies suggest that a
      cascade initiating with PKC activation is responsible for modifying transcription
      factors that interact with regulatory sequences in the collagen II gene. A
      detailed understanding of the factors involved in cartilage-specific gene
      regulation in chondrocytes would facilitate development of therapeutic protocols
      for the repair of degenerated cartilage in diseases such as osteoarthritis.

PMID- 8263030
TI  - Disparate modulation of plasma membrane protein lateral mobility by various cell
      permeabilizing agents.
AB  - The mobility of a cell surface protein on cells osmotically swollen by treatment
      with several different cell permeabilizing agents retains specific restraints
      despite detachment of the plasma membrane from the cortical cytoskeleton.
      Fluorescence photobleaching recovery experiments indicate that the lateral
      diffusion constants of immunoglobulin E (IgE)-receptor complexes on the surface
      of rat basophilic leukemia cells increase 2-5x following permeabilization with
      streptolysin O or digitonin, with little change in their mobile fractions.
      Swelling by hypo-osmotic treatment in water enhances lateral diffusion of IgE
      receptor complexes and raises the mobile fractions to near 100%. In contrast,
      swelling by treatment with filipin arrests lateral diffusion, although rotational
      mobility remains unhindered. Lateral mobility of a fluorescent lipid analogue
      remains unchanged under these conditions. Crosslinking by anti-IgE antibodies
      redistributes the IgE-receptor complexes into large patches on untreated cells
      and on cells swollen by permeabilization with streptolysin O or digitonin, but
      not on cells swollen by treatment with filipin. The results indicate a diversity
      of effects of the various permeabilizing agents on the mobility of membrane
      proteins. In particular, treatment with filipin appears to reorganize the plasma
      membrane into a network of fluid domains on a scale smaller than the bleaching
      spot size used (approximately 1.5 microns).

PMID- 8263031
TI  - Migratory interaction of amphibian epidermal cells with components of the
      basement membrane.
AB  - In adult newts, basal epidermal cells adjacent to a fresh wound move toward the
      damaged area by migrating over the epidermal basement membrane. In an attempt to
      determine which basement membrane components mediate this migration, small pieces
      of glass coated with various natural matrices, purified proteins, or fragments of
      proteins were implanted into skin wounds such that epidermal cells attempting to
      form a wound epithelium would encounter the implants. Laminin derived from a cell
      line (M1536-B3) that produces no type IV collagen was inactive as a migration
      substrate. Migration on recombinant entactin was somewhat better than on laminin
      but was still only approximately 14% of that on type I collagen. M15 matrix, a
      laminin and entactin-containing product of M1536-B3 cells, was no better than
      entactin alone. Type IV collagen was an excellent substrate, producing slightly
      more migration than corresponding concentrations of type I collagen at nearly all
      concentrations tested. Migration on type IV lacking the NC1 domain was at least
      as good as on intact type IV. All the activity in type IV was present in a 95 kD
      fragment (alpha 1(IV)95) from the carboxy terminal two-thirds of the alpha 1
      chain. Approximately 60% of the activity on alpha 1(IV)95 was obtained on
      implants coated with a 110 amino acid fragment of the alpha 1 chain derived from
      the carboxy terminal half of alpha 1(IV)95. Adding the synthetic peptide, arg-gly
      asp-ser (RGDS) to the medium, blocked migration on fibronectin-coated implants
      but had no effect on implants coated with type IV, suggesting that migration on
      type IV involves different cell surface receptors than those mediating migration
      over fibronectin. Matrigel, a commercial product containing most basement
      membrane components, was a poor migration substrate. Thus if type IV mediates
      basal cell migration toward a wound in vivo, there may have to be some
      alterations in basement membrane structure to allow epidermal receptors to access
      type IV active site(s).

PMID- 8263032
TI  - Organization of calsequestrin-positive sarcoplasmic reticulum in rat
      cardiomyocytes in culture.
AB  - The sarcoplasmic reticulum (SR) regulates the levels of cytoplasmic free Ca2+
      ions in muscle cells. Calsequestrin is a major Ca(2+)-storing protein and is
      localized at special sites in the SR. To investigate the development of
      calsequestrin-positive SR and its interaction with the cytoskeleton, we examined
      the distribution of calsequestrin in cultured cardiomyocytes from newborn rats by
      immunofluorescence with anticalsequestrin and antitubulin antibodies and
      rhodamine-phalloidin. In frozen sections of neonatal rat heart, anticalsequestrin
      immunostaining was apparent as cross-striations at Z-lines. When newborn
      cardiomyocytes were isolated, calsequestrin-positive SR was disorganized and was
      apparent as small vesicles beneath the sarcolemma, whereas myofibrils accumulated
      in the center of the cells. As the cells spread in culture, calsequestrin
      positive vesicles spread to the periphery of the cytoplasm, becoming associated
      with the developing myofibrils. In mature cells, calsequestrin was closely
      associated with myofibrils, showing cross-striations at the Z-lines. Double
      labeling using anticalsequestrin and antitubulin antibodies demonstrated that the
      distribution of calsequestrin-positive structures was similar to that of the
      microtubular arrays. When the microtubules were depolymerized by nocodazole at an
      early stage, the extension of the SR to the cell periphery was inhibited. In
      mature cardiomyocytes, nocodazole appeared not to affect the distribution of the
      SR. These results indicate that the calsequestrin-positive SR in cardiomyocytes
      is organized at the proper sites of myofibrils during myofibrillogenesis and that
      the microtubules might serve as tracts for the transport of components of the SR.

PMID- 8263033
TI  - Phorbol 12-myristate 13-acetate stimulates proliferation and ductal morphogenesis
      and inhibits functional differentiation of normal rat mammary epithelial cells in
      primary culture.
AB  - The effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) on
      proliferation and differentiation of normal mammary epithelial cells from 50-day
      old virgin rats was investigated using a model system that allows for full
      morphological and functional development of the cells. In this model, mammary
      epithelial cells are grown within a reconstituted basement membrane in a defined
      serum-free medium. PMA at a concentration of 10(-6) M effected translocation of
      protein kinase C from cytosol to membrane. At the same concentration, it
      stimulated cell proliferation both in the presence and absence of EGF, and this
      stimulation was observed even when PMA exposure was limited to 15 min at the time
      of each media change. In contrast to the effect on proliferation, PMA at
      concentrations of 10(-7) and 10(-6) M inhibited functional differentiation as
      assessed by casein accumulation. Phorbol 12,13-dibutyrate at 10(-6) M also
      stimulated proliferation and inhibited casein accumulation and was more effective
      than PMA in both cases. In contrast, the nonactive tumor promoter 4-alpha PMA had
      no effect on either proliferation or differentiation. One of the most striking
      effects of PMA was its ability to stimulate an atypical ductal morphogenesis, as
      manifested by the formation of intricate web-like colonies, and to inhibit the
      development of the well-differentiated alveolar-like multilobular colonies. PMA
      was also shown to completely suppress the growth of the squamous-like colonies
      that develop when EGF is absent or deficient. These effects of phorbol esters in
      mammary epithelial cells to stimulate proliferation, inhibit functional
      differentiation, and stimulate the development of ductal colonies are consistent
      with the suggestion that the signal transduction pathways evoked by PMA could act
      to stimulate the growth of initiated cells or render normal cells more sensitive
      to carcinogen.

PMID- 8263034
TI  - Insulin stimulates GDP release from G proteins in the rat and human liver plasma
      membranes.
AB  - Plasma membranes (1-2 mg protein) prepared from the livers of adult male rats and
      human organ donors were incubated with 0.6 microM [alpha-32P] guanosine
      triphosphate (GTP) in an adenosine triphosphate (ATP)-regenerating buffer at 37
      degrees C for 1 h; during this incubation, the [32P]GTP is hydrolyzed and the
      nucleotide that is predominantly bound to the membranes is [32P] guanosine
      diphosphate (GDP). [32P]GDP release from the liver membranes was proportional to
      the protein concentration and increased as a function of time. At 5 mM, Ca2+,
      Mg2+, Mn2+, and Zn2+ maximally inhibited GDP release by 80-90%, whereas, 5 mM
      Cu2+ maximally stimulated the reaction by 100%. Therefore, cations were not
      included in the buffer used in the GDP release step. One microM Gpp(NH)p (5'
      guanylylimidodiphosphate), a nonhydrolyzable analog of GTP, maximally stimulated
      [32P]GDP release in the liver membranes by up to 30%. Although 10 nM Gpp(NH)p had
      no effect on GDP release, it appeared to stabilize the hormonal effect by
      blocking further GDP/GTP exchange. In the rat membranes, 1-100 nM glucagon (used
      as a positive control) stimulated [32P]GDP release by about 17% (P < .05);
      similarly, 0.1-100 nM insulin stimulated [32P]GDP release by 10-13% (P < .05). In
      the human membranes, 10 pM to 100 nM insulin stimulated [32P]GDP release by 7
      10%. In the rat membranes, 10 nM insulin stimulated [32P]GDP release by 17 and
      24% at 2 and 4 min, respectively (P < .05); in the human membranes, 10 nM insulin
      stimulated [32P]GDP release by about 9% at 2 and 4 min.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263035
TI  - Induction of osteoprogenitor cell differentiation in rat marrow stroma increases
      mitochondrial retention of rhodamine 123 in stromal cells.
AB  - Bone marrow stromal cells contain colony forming cells with the potential to
      differentiate into osteoprogenitor (OPC) cells. OPC-stimulation medium,
      containing dexamethasone, ascorbate, and beta-glycerophosphate is widely used to
      recruit OPCs in culture. Cultures were incubated 24 h with rhodamine 123 (Rho),
      on different days, to examine the effect of the OPC-stimulation medium on the
      mitochondrial membrane potential of stromal cells. Cultures grown in both
      ordinary medium (DMEM with 15% FCS) and OPC-stimulation medium showed 2 Rho
      retention peaks on days 3-4 and 10-11. Between days 5 and 10 there was a drop in
      Rho retention/cell. OPC-stimulation medium increased Rho retention by at least
      twice the amount relative to ordinary medium, and has quadrupled it on day 7.
      Incubation with Rho concentrations above 5.0 micrograms/ml inhibited the portion
      of increased Rho retention which was contributed by the OPC-stimulation medium.
      Prolonged exposure to 0.1, 1.0, and 10.0 micrograms/ml Rho for 12 days only
      slightly increased day 12 ALP activity/cell, had no effect on day-21
      mineralization and only the high dose, 10.0 micrograms/ml, doubled stromal cell
      proliferation. Under 24 h incubation Rho concentrations of 1.0 microgram/ml and
      below can serve as a marker for mitochondrial membrane potential in
      differentiating stromal cells. The results indicate that under both culture
      conditions stromal cell mitochondria undergo cycles of high and low membrane
      potential states and that the OPC-stimulation medium constantly maintains an
      elevated membrane potential relative to ordinary medium.

PMID- 8263036
TI  - Nitric oxide production from a macrophage cell line: interaction with autologous
      and allogeneic lymphocytes.
AB  - The indirect stimulation of macrophages to produce nitrite was examined by using
      the macrophage cell line J774.J774 spontaneously produced nitrite, when cultured
      at high concentration. J774 cultured in low concentration (< 10(4) cells in 100
      microliters) barely produced nitrite. J774 cultured in low concentration produced
      a large amount of nitrite by the co-culture of nonadherent spleen cells or
      nonadherent peritoneal exudate cells, which were stimulated with con A, anti-CD3,
      or staphylococcal enterotoxin A. J774 (BALB/c derived: H-2d) cultured with either
      syngeneic (BALB/c) or allogeneic (B6; H-2b B10BR; H-2k) nonadherent lymphocytes,
      which were stimulated with conA or anti-CD3, produced nitric oxide. However, J774
      produced nitric oxide by stimulation with SEA only when co-cultured with SEA
      reactive T lymphocytes. Peritoneal exudate cells from mice, which did not
      proliferate by the stimulation of conA or anti-CD3, proliferated well by the
      addition of L-arginine homologue, NG-monomethyl-L-arginine. The proliferation of
      nonadherent peritoneal exudate cells stimulated with conA or anti-CD3 was
      suppressed by the addition of peritoneal macrophages. This suppression was
      abolished by the addition of NG-monomethyl-L-arginine.

PMID- 8263037
TI  - Purification and characterization of NADPH-cytochrome P-450 reductase from rat
      epidermis.
AB  - NADPH-cytochrome P-450 oxidoreductase (P-450 red) transfers reducing equivalents
      from NADPH to cytochrome P-450 (P-450) in the monooxygenase system. Detergent
      solubilized proteins from the membrane fraction of neonatal rat epidermis were
      purified by 2',5'-ADP-agarose affinity column chromatography. The purified
      protein showed an apparent homogeneity on sodium dodecylsulfate-polyacrylamide
      gel electrophoresis and molecular weight was estimated to be 78 kDa. NADPH
      cytochrome c reductase activity increased by 95-fold in the purified enzyme.
      Epidermal P-450 red in vitro reconstituted benzo(a)pyrene hydroxylase activity in
      a dose dependent manner with P-450 purified from either rat liver or epidermis.
      Western blot analysis demonstrated that epidermal P-450 red immunologically cross
      reacts to liver P-450 red. Immunohistochemical staining showed that the enzyme
      was predominantly localized in the epidermis. The intensity of
      immunohistochemical staining of rat skin sections and tissue distribution did not
      change in the skin treated with beta-naphthoflavone, which results in a
      substantial increase in P-450 1A1 activity. Quantitative assessment of P-450 red
      in treated and untreated epidermis also showed no change. These findings indicate
      that constitutive P-450 red, fully capable of supporting P-450, exists in rat
      epidermis, and can function in metabolism of endogenous and exogenous compounds.

PMID- 8263038
TI  - Fluorescent in situ hybridization of the telomere repeat sequence in hamster
      sperm nuclear structures.
AB  - The flat, hooked-shaped architecture of the hamster sperm nucleus makes this an
      excellent model for in situ hybridization studies of the three dimensional
      structure of the genome. We have examined the structure of the telomere repeat
      sequence (TTAGGG)n with respect to the various nuclear structures present in
      hamster spermatozoa, using fluorescent in situ hybridization. In fully condensed,
      mature sperm nuclei, the telomere sequences appeared as discrete spots of various
      sizes interspersed throughout the volume of the nuclei. While the pattern of
      these signals was non-random, it varied significantly in different nuclei. These
      discrete telomere foci were seen to gradually lengthen into linear, beaded
      signals as sperm nuclei were decondensed, in vitro, and were not associated with
      the nuclear annulus. We also examined the relationship of telomeres to the sperm
      nuclear matrix, a residual nuclear structure that retains the original size and
      shape of the nucleus. In these structures the DNA extends beyond the perimeter of
      the nucleus to form a halo around it, representing the arrangement of the
      chromosomal DNA into loop domains attached at their bases to the nuclear matrix.
      Telomere signals in these structures were also linear and equal in length to
      those of the decondensed nuclei, and each signal represented part of a single DNA
      loop domain. The telomeres were attached at one end to the nuclear matrix and
      extended into the halo. Sperm nuclear matrices treated with Eco RI retained the
      telomere signals. These data support sperm DNA packaging models in which DNA is
      coiled into discrete foci, rather than spread out linearly along the length of
      the sperm nucleus.

PMID- 8263039
TI  - Role of protein phosphorylation in TNF-induced apoptosis: phosphatase inhibitors
      synergize with TNF to activate DNA fragmentation in normal as well as TNF
      resistant U937 variants.
AB  - This study examined the role of protein phosphorylation in TNF induction of
      apoptosis in several tumor cell lines by testing the effects of agents that
      either stimulate or inhibit protein phosphorylation. The serine-threonine
      phosphatase inhibitors, okadaic acid (OKA) and calyculin A (CLA), synergistically
      augmented TNF-induced apoptosis in several TNF-sensitive tumor cell lines
      including the U937 histiocytic lymphoma, the BT-20 mammary carcinoma, and the
      LNCap prostatic tumor cell line. Furthermore, the phosphatase inhibitors
      completely reversed the TNF resistance of a variant (U9-TR) derived from U937.
      CLA also inhibited phosphatase activity in cell-free extracts from both U937 and
      U9-TR at the same concentrations (0.4-2.0 nM) that it synergized with TNF. In
      contrast, TNF treatment of U937 cells did not result in inhibition of phosphatase
      activity mediated by protein phosphatase 1 (PP1) and PP2A in cell extracts. Since
      the phosphatase inhibitors are known to increase the overall levels of protein
      phosphorylation in cells, this suggested that TNF may act by stimulating protein
      kinase (PK) activity. This hypothesis was supported by the results of testing a
      panel of relatively specific protein kinase inhibitors. TNF activation of DNA
      fragmentation was blocked by a potent inhibitor of myosin light chain kinase
      (MLCK) but was unaffected by inhibitors of cAMP or cGMP-dependent PKs. We
      postulate that a defect in the activation of MLCK or possibly some other as yet
      unknown PK may be responsible for the TNF resistance of U9-TR. Furthermore, this
      resistance may be circumvented by promoting protein phosphorylation with the
      serine-threonine-dependent phosphatase inhibitors.

PMID- 8263040
TI  - 1 alpha,25-dihydroxyvitamin D3-induced changes in intracellular pH in osteoblast
      like cells modulate gene expression.
AB  - 1 alpha,25-Dihydroxyvitamin D3 exerts rapid nongenomic effects on rat osteoblast
      like cells independent of the classic nuclear receptor. These effects include
      changes in phospholipid metabolism and cell calcium. Intracellular calcium itself
      has been proposed to regulate intracellular pH in osteoblast cell lines. The
      purpose of this study was to determine the effect of 1 alpha,25-dihydroxyvitamin
      D3 on intracellular pH, the relationship of changes in calcium to changes in pH,
      and the role of pH changes in genomic activation. 1 alpha,25-Dihydroxyvitamin D3
      increased intracellular pH within 10 min in rat osteoblast-like cells, an effect
      that was inhibited by removal of extracellular sodium and by the biologically
      inactive epimer 1 beta,25-dihydroxyvitamin D3. The hormone increased
      intracellular calcium in Quin 2 loaded cells in the presence and absence of
      extracellular sodium. The 1 alpha,25-dihydroxyvitamin D3-induced increments in
      osteocalcin and osteopontin mRNA levels were abolished in sodium-free medium. The
      results indicate that 1 alpha,25-dihydroxyvitamin D3-induced increments in
      cellular calcium precede cell alkalinization and that these changes in
      intracellular pH may modulate steady-state mRNA levels of genes induced by
      vitamin D.

PMID- 8263041
TI  - Identification and characterization of two proximal elements in the rat
      osteocalcin gene promoter that may confer species-specific regulation.
AB  - The rat osteocalcin gene encodes a 6-kD osteoblast-specific protein that is
      expressed post-proliferatively. The developmental and steroid hormone responsive
      expression of the osteocalcin gene is transcriptionally regulated by a promoter
      with multiple basal and enhancer elements that exhibit activity controlled by a
      series of physiological mediators (e.g., 1.25(OH)2D3, glucocorticoids). In this
      study, we established the contribution of the rat osteocalcin (OC) box domain (
      99 to -76), a proximal basal element with a CCAAT motif as a central core, to
      transcriptional activity of the rat osteocalcin gene with in vivo co-transfection
      assays. By this same assay, however, the highly homologous (22 of 24 nt) human OC
      box element was unable to compete for transcription factor binding with the rat
      OC promoter. In vitro protein/DNA interaction studies confirm the presence of two
      protein binding sites in the OC box region, one of which overlaps the CCAAT motif
      and, at least in part, accounts for species-specific expression. Competition
      analysis established that the single nucleotide substitution of adenine for
      thymine, which converts the core motif of the rat OC box (CCAAT) to the core
      motif of the human OC box (CCAAA), accounts for observed species differences in
      transcription factor interactions. The CCAAT-specific protein/DNA interactions
      are heat stable and insensitive to phosphatase treatment. At second protein/DNA
      interaction located upstream of the CCAAT motif includes two steroid-like half
      elements. These interactions are heat labile and sensitive to phosphatase
      treatment in contrast to the CCAAT-specific interactions. The human OC promoter
      contains only a single steroid-like half-element, while two steroid half-elements
      with an 11 nucleotide spacer are present in the rat OC promoter. These observed
      variations in sequence organization and transactivation factor binding in
      analogous proximal basal regulatory regions of the OC gene promoter may provide a
      basis for species-restricted variations in responsiveness to physiological
      mediators of OC gene expression at the transcriptional level.

PMID- 8263042
TI  - Differential distribution of vesicular carriers during differentiation and
      synapse formation.
AB  - Coated and noncoated vesicles participate in cellular protein transport. Both
      acetylcholine receptors (AChR) and acetylcholinesterase (AChE) are transported
      via coated vesicles, some of which accumulate beneath the neuromuscular synapse
      where AChRs cluster. To investigate the mechanisms by which these proteins are
      transported during postsynaptic remodeling, we purified coated vesicles from the
      bovine brain via column chromatography (Sephacryl S-1000) and raised monoclonal
      antibodies to epitopes of the vesicular membranes enriched in AChE. We assayed
      for AChE (coated vesicle enriched), hexosaminidase (lysosomal contaminants), NADH
      cytochrome C reductase (mitochondrial containing), and protein and demonstrated
      electron microscopically using negative staining that the vesicular fraction
      contained 95% pure coated vesicles. We then injected coated vesicle fractions and
      the fractions from which the coat was removed intraperitoneally into mice and
      obtained three monoclonal antibodies: C-33, C-172, and F-22. On immunoblots of
      purified vesicles and cultured skeletal muscle, mAb C-33 stained a 180 Kd band
      and mAb C-172 stained a 100 kd band. MAb F-22 stained 50 kd and 55 kd bands and
      was not characterized further. Immunofluorescent microscopy with C-33 and C-172
      revealed punctate fluorescence whose distribution depends upon the stage of
      myotube development. Four days after plating, myotubes showed punctate
      fluorescence throughout the myotube, whereas those stained 8 days after plating
      showed a punctate perinuclear distribution. Myotubes innervated by ciliary
      neurons show punctate fluorescence limited to the nuclear periphery and most
      concentrated around nuclei which line up beneath neuronal processes. This
      differential vesicular distribution, observed during myotube differentiation and
      innervation, suggests that these vesicles participate in vesicular membrane
      traffic.

PMID- 8263043
TI  - Extracellular annexin II is associated with divalent cation-dependent tumor cell
      endothelial cell adhesion of metastatic RAW117 large-cell lymphoma cells.
AB  - Using fixed microvessel endothelial cell monolayers the molecules involved in the
      adhesion of liver-preferring murine RAW117 large cell lymphoma cells to murine
      liver-derived microvessel endothelial cells were identified by affinity
      isolation. Detergent lysates obtained from poorly (P) or highly (H10) liver
      metastatic cells inhibited RAW117-H10 cell adhesion to hepatic sinusoidal
      endothelial (HSE) cell monolayers. Allowing detergent lysates of cell surface
      labeled RAW117 cells to bind to fixed HSE cell monolayers and eluting the bound
      components indicated that several tumor cell surface molecules (approximately 70,
      approximately 35, approximately 32, approximately 22, and approximately 14 kDa)
      might be involved in RAW117 cell-HSE cell adhesion. The approximately 35 kDa
      component was cation dependent in its binding to target HSE cells. Increasing
      detergent concentration had no effect on binding of the approximately 35 kDa
      component to HSE cell monolayers, whereas treatment with 0.5 M NaCl resulted in
      its selective elution from HSE cells. Incubation of the HSE cell monolayers with
      detergent lysates from cell surface-labeled RAW117-H10 cells resulted in
      selective depletion of the approximately 35 kDa component, suggesting that the
      binding is saturable. This divalent cation-dependent molecule is one of the major
      tumor cell surface components bound by several types of endothelial cells and
      murine hepatocytes, whereas there was poor binding of this component to unfixed
      or fixed human red blood cells. The purified, partially (approximately 40%)
      sequenced molecule had amino acid sequence identity with murine but not bovine
      annexin II, indicating that it was not bound from the bovine serum used to grow
      RAW117 cells. Using antibodies specific for annexin II flow cytometry indicated
      equivalent amounts of annexin II are expressed on RAW117 cell surfaces in the
      absence or presence of excess EDTA, whereas annexin I was only found in low
      amounts on the surfaces of RAW117 cells. Annexin II antibodies inhibited by
      approximately 40-50% the adhesion of RAW117 tumor cells to live or fixed
      endothelial cells, and purified tumor cell surface fractions containing the
      approximately 35 kDa component partially inhibited (approximately 35%) RAW117
      cell-HSE cell adhesion. The data indicate that annexin II is expressed on the
      extracellular surface of RAW117 cells, and cell surface-annexin II mediates a
      portion of the Ca(2+)-dependent RAW117 cell adhesion to liver microvessel
      endothelial cells.

PMID- 8263044
TI  - Increased densities of binding sites for the "peripheral-type" benzodiazepine
      receptor ligand [3H]PK11195 in vulnerable regions of the rat brain in thiamine
      deficiency encephalopathy.
AB  - Quantitative receptor autoradiography was used to evaluate the density of high
      affinity binding sites for the "peripheral-type" benzodiazepine receptor (PTBR)
      ligand [3H]PK11195 in brain regions of the rat at different stages of
      pyrithiamine-induced thiamine deficiency encephalopathy, an experimental model of
      the Wernicke-Korsakoff syndrome (WKS). Assessment of the density of [3H]PK11195
      binding sites in thiamine-deficient animals showing no neurologic signs of
      thiamine deficiency encephalopathy, and revealed no significant alterations
      compared with pair-fed control animals in any brain region studied. Densities of
      [3H]PK11195 binding sites were, however, significantly increased in brain regions
      of the rat at the symptomatic stage, where increased densities were seen in the
      inferior colliculus (233% increase, p < 0.001), inferior olivary nucleus (154%
      increase, p < 0.001) and thalamus (up to 107% increase, p < 0.001). Histologic
      studies of these same brain regions revealed evidence of neuronal cell loss and
      concomitant gliosis. Densities of [3H]PK11195 binding sites in nonvulnerable
      brain regions that showed no histologic evidence of neuronal loss, such as the
      cerebral cortex, hippocampus, and caudate-putamen, were not significantly
      different from those in control animals. Increased densities of binding sites for
      the PTBR ligand probably reflect glial proliferation and are consistent with an
      excitotoxic mechanism in the pathogenesis of neuronal cell loss in thiamine
      deficiency encephalopathy. Positron emission tomography (PET) using [11C]PK11195
      could offer a potentially useful diagnostic tool in WKS in humans.

PMID- 8263045
TI  - The human brain GLUT1 glucose transporter: ultrastructural localization to the
      blood-brain barrier endothelia.
AB  - Immunogold electron microscopy was used to examine human brain resections to
      localize the GLUT1 glucose transporter. The tissue examined was obtained from a
      patient undergoing surgery for treatment of seizures, and the capillary profiles
      examined had characteristics identical to those described previously for active,
      epileptogenic sites (confirmed by EEG analyses). A rabbit polyclonal antiserum to
      the full-length human erythrocyte glucose transporter (GLUT1) was labeled with 10
      nm gold particle-secondary antibody conjugates and localized immunoreactive GLUT1
      molecules in human brain capillary endothelia, with < 0.25% of the particles
      beyond the capillary profile. Erythrocyte membranes were also highly
      immunoreactive, whereas macrophage membranes were GLUT1-negative. The number of
      immunoreactive sites per capillary profile was observed to be 10-fold greater in
      humans than in previous studies of rat and rabbit brain capillaries. In addition,
      half of the total number of immunoreactive gold particles were localized to the
      luminal capillary membrane. We suggest that the blood-brain barrier GLUT1 glucose
      transporter is up-regulated in seizures, and this elevated transporter activity
      is characterized by increased GLUT1 transporters, particularly on the luminal
      capillary membranes. In addition, acute modulation of glucose transporter
      activity is presumed to involve translocation of GLUT1 from cytoplasmic to
      luminal membrane sites, demonstrable with quantitative immunogold electron
      microscopy.

PMID- 8263046
TI  - Brain glucose levels in portacaval-shunted rats with chronic, moderate
      hyperammonemia: implications for determination of local cerebral glucose
      utilization.
AB  - Rates of glucose utilization (lCMRglc) in many structures of the brain of fed,
      portacaval-shunted rats, when assayed with the [14C]deoxyglucose (DG) method in
      our laboratory, were previously found to be unchanged (30 of 36 structures) or
      depressed (6 structures) during the first 4 weeks after shunting, but to rise
      progressively to higher than normal values in 25 of 36 structures from 4-12
      weeks. In contrast, lCMRglc, when assayed with the [14C]glucose method in another
      laboratory, was depressed in most structures of brains of 4-8-week shunted rats
      that had relatively high brain ammonia levels. There was a possibility that the
      increases in lCMRglc obtained with the [14C]DG method may have been artifactual,
      due, in part, to a change in brain glucose content which could alter the value of
      the lumped constant of the DG method. Brain glucose levels of shunted rats were,
      therefore, assayed by both direct chemical measurement in freeze-blown samples
      and by determination of steady-state brain:plasma distribution ratios for
      [14C]methylglucose; the methylglucose distribution ratio varies as a function of
      plasma and tissue glucose contents. Within a week after shunting, ammonia levels
      in blood and brain rose to 0.25-0.30 mM and 0.35-0.70 mumol/g, respectively, and
      mean plasma glucose levels fell from 9-10 mM to 7.4-8.5 mM, and then remained
      nearly constant. Brains of fed-shunted rats had normal glycogen levels and stable
      but moderately reduced glucose contents between 1 and 12 weeks (i.e., 1.9-2.2
      mumol/g). [14C]Methylglucose distribution ratios were essentially the same as
      those in controls in 22 brain structures at 2 and 8 weeks after shunting. Because
      brain glucose levels remained stable from 1 to 12 weeks after shunting, there is
      no evidence to support the hypothesis that the value of the lumped constant would
      have changed and caused an artifactual rise in lCMRglc.

PMID- 8263047
TI  - Cortical negative DC deflections following middle cerebral artery occlusion and
      KCl-induced spreading depression: effect on blood flow, tissue oxygenation, and
      electroencephalogram.
AB  - In the periphery of ischemic brain lesions, transient spreading depression-like
      direct current (DC) deflections occur that may be of pathophysiological
      importance for determining the volume of the ischemic infarct. The effect of
      these deflections on cerebral blood flow, tissue oxygen tension, and
      electrophysiology was studied in rats submitted to intraluminal thread occlusion
      of the middle cerebral artery (MCA) and compared with the changes following
      potassium chloride (KCl)-induced spreading depression of intact animals.
      Immediately after MCA occlusion, cortical laser-Doppler flow (LDF) in the
      periphery of the MCA territory sharply decreased to 35 +/- 14% of control (mean
      +/- SD; p < 0.05), tissue PO2 declined from 28 +/- 4 to 21 +/- 3 mm Hg (p <
      0.05), and EEG power fell to approximately 80% of control. During 7-h occlusion,
      3-11 DC deflections with a mean duration of 5.2 +/- 4.8 min occurred at irregular
      intervals, and EEG power gradually declined to 66 +/- 16% of control (p < 0.05).
      During the passage of DC deflections, LDF did not change, but PO2 further
      declined to 19 +/- 4 mm Hg (p < 0.05). KCl-induced depolarizations of intact rats
      were significantly shorter (1.4 +/- 0.5 min; p < 0.05) and were accompanied by a
      43% increase in LDF (p < 0.05) and a slight but significant increase in tissue
      PO2 from 22 +/- 4 to 25 +/- 4 mm Hg (p < 0.05). The comparison of periinfarct and
      KCl-induced depolarizations demonstrates that oxygen requirements are not coupled
      to an appropriate flow response in the periinfarct zone with severely reduced
      blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263048
TI  - Brain metabolism during short-term starvation in humans.
AB  - During prolonged starvation, brain energy requirements are covered in part by the
      metabolism of ketone bodies. It is unknown whether short-term starvation of a few
      days' duration may lead to reduced brain glucose metabolism due to the change
      toward ketone body consumption. In the present study we measured the cerebral
      metabolism of glucose and ketone bodies in nine healthy volunteers before and
      after 3.5 days of starvation. Regional glucose metabolism was measured by dynamic
      positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. The mean
      value of K1* in gray and white matter increased by 12% (p < 0.05), whereas k2*
      and k3* were unchanged compared with control values. Regional glucose metabolism
      in cortical gray matter was reduced by 26% from 0.294 +/- 0.054 to 0.217 +/-
      0.040 mumol g-1 min-1 (p < 0.001). White matter glucose metabolism decreased by
      27% (p < 0.02). The decrease was uniform in gray and white matter with regional
      decreases ranging from 24 to 30%. A determination using Fick's principle
      confirmed the reduction in glucose metabolism yielding a decrease of 24% from
      0.307 +/- 0.050 to 0.233 +/- 0.073 mumol g-1 min-1 (p < 0.05), whereas CBF did
      not change (0.57 +/- 0.07 vs. 0.57 +/- 0.06 ml g-1 min-1). The global net uptake
      of beta-hydroxybutyrate increased 13-fold from 0.012 +/- 0.024 to 0.155 +/- 0.140
      mumol g-1 min-1 (p < 0.05). Net uptake of acetoacetate and net efflux of lactate
      and pyruvate did not change significantly during starvation. The present study
      shows that the human brain adapts to the changes in energy supply as early as 3
      days following initiation of starvation, at which time ketone bodies account for
      approximately one-fourth of the cerebral energy requirements.

PMID- 8263049
TI  - Functional metabolic mapping of the rat brain during unilateral electrical
      stimulation of the subthalamic nucleus.
AB  - The alterations in local metabolic activity of several anatomically distinct
      brain areas were investigated by means of the quantitative autoradiographic 2
      deoxy-D-[1-14C]glucose method in awake rats during unilateral electrical
      stimulation of the subthalamic nucleus (STH). Unilateral electrical stimulation
      of the STH induced local metabolic activation (by 70% as compared with the
      control group), as well as distal metabolic activations in the substantia nigra
      reticulata (by 34%), globus pallidus (by 19%), entopeduncular nucleus (by 18%),
      deep layers of the superior colliculi (by 15%), and parafascicular thalamic
      nucleus (by 18%), ipsilaterally to the stimulated side. The ventrolateral motor
      thalamic nucleus as well as the limbic components, posterior cingulate cortex,
      and anteroventral thalamic nucleus displayed bilateral metabolic activations (by
      20-28%). These results indicate that, in addition to its known ipsilateral motor
      connections, each STH is functionally related to the limbic system bilaterally.
      It is suggested that the STH is a site where the central motor information is
      accessible to the limbic system. Quantitative image analysis of individual serial
      sections in the STH, substantia nigra, and globus pallidus revealed a consistent
      dorsoventral pattern of topographic interrelations. Stimulation of either the
      dorsal or the ventral subdivision of the STH induced always stronger activation
      in the dorsal compartment of the substantia nigra and in the ventral compartment
      of the globus pallidus. These results suggest that the earlier-described
      inversion of the dorsoventral functional correspondence between the substantia
      nigra and globus pallidus may be partly mediated via the subthalamic nerve cells
      projecting collateral axons to both these areas.

PMID- 8263050
TI  - Modulation of intracellular formation of reactive oxygen intermediates in
      peritoneal macrophages and microglia/brain macrophages by propentofylline.
AB  - Ischemia-induced nerve cell death can partly be prevented by propentofylline, a
      pharmacon structurally related to xanthine derivates that interacts with the
      neuromodulatory function of endogenous adenosine. To evaluate a possible
      mechanism of neuroprotection by propentofylline, we studied its effect on the
      cellular production of reactive oxygen intermediates in microglial cells, which
      under pathological conditions can differentiate into brain macrophages, in
      comparison to peritoneal macrophages. Using a flow cytometric assay, we
      determined the intracellular formation of reactive oxygen intermediates by
      measuring the oxidation of the membrane-permeable and nonfluorescent
      dihydrorhodamine 123 to the cationic and intracellularly trapped, green
      fluorescent rhodamine 123 in single viable cells. Propentofylline at the
      therapeutic concentration of 50 microM completely inhibited the Ca(2+)-dependent
      Con A-induced increase in the production of reactive oxygen intermediates in
      peritoneal macrophages. In isolated and cultured microglial cells, which have a
      high spontaneous respiratory burst activity, the spontaneous production of
      reactive oxygen intermediates was reduced by approximately 30%. A phorbol 12
      myristate 13-acetate-induced rise in the respiratory burst activity could not be
      inhibited by propentofylline in either cell type. An increased generation of
      reactive oxygen intermediates is thought to contribute to nerve cell death after
      brain ischemia, edema, and neurodegenerative diseases like Alzheimer's disease.
      These pathological conditions are all accompanied by an activation of microglial
      cells. We therefore suggest that the neuroprotective properties of
      propentofylline might in part be due to a modulation of the microglial production
      of potentially harmful reactive oxygen intermediates.

PMID- 8263051
TI  - Prostaglandin E1 induces c-Fos and Myc proteins and protects rat hippocampal
      cells against hypoxic injury.
AB  - We investigated the effects of prostaglandin (PG) E1 on the hypoxic injury of
      fetal rat hippocampal cells. Primary hippocampal cell cultures (embryonic day 18)
      were established and maintained. After 72 h in culture, PGE1 was added to the
      serum-free medium at a final concentration of 10(-5)-10(-9) M. Cultures were
      divided into two groups: The normoxia group was in culture for another 48 h, and
      the hypoxia group was exposed to 24 h of hypoxia followed by continuation of
      culture for another 24 h. As a quantitative measure of cell death, lactate
      dehydrogenase (LDH) activity was estimated in the culture medium. The LDH
      activity, released by the hypoxic insult, was significantly smaller with PGE1
      treatment at 10(-6), 10(-7), and 10(-8) M (p < 0.01) and 10(-9) M (p < 0.05)
      compared with the control. No differences in the LDH activities were observed in
      the normoxia group. Glial culture was not affected by the hypoxia. Western blot
      analysis showed an increased induction of 62-kDa c-Fos and 58, 60, and 66 kDa Myc
      proteins in rat hippocampal cells with 10(-7) M PGE1 treatment. We conclude that
      PGE1 at concentrations of 10(-6)-10(-9) M protects rat hippocampal neurons
      against hypoxic insult.

PMID- 8263052
TI  - Effects of MK-801 and NBQX on acute recovery of piglet cerebral metabolism after
      hypothermic circulatory arrest.
AB  - Brain protection during open heart surgery in the neonate and infant remains
      inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and
      NBQX on recovery of brain cellular energy state and metabolic rates were
      evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing
      cardiopulmonary bypass and hypothermic circulatory arrest at 15 degrees C
      nasopharyngeal temperature for 1 h, as is used clinically for repair of
      congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3
      dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline] (25 mg/kg) was given
      intravenously before cardiopulmonary bypass. Equivalent doses were placed in the
      cardiopulmonary bypass prime plus continuous infusions after reperfusion (0.15 mg
      kg-1h-1 and 5 mg kg-1h-1). Changes in high-energy phosphate concentrations and pH
      were analyzed by magnetic resonance spectroscopy in 17 animals until 225 min
      after reperfusion. Cerebral blood flow determined by radioactive microspheres as
      well as cerebral oxygen and glucose consumption were studied in 17 other animals.
      Cerebral blood flow and oxygen consumption were depressed relative to control by
      both MK-801 and NBQX at baseline. Recovery of phosphocreatine (p = 0.010), ATP (p
      = 0.030), and intracellular pH (p = 0.004) was accelerated by MK-801 and retarded
      by NBQX over the 45 min of rewarming reperfusion and the first hour of
      normothermic reperfusion. The final recovery of ATP at 3 h and 45 min reperfusion
      was significantly reduced by NBQX (46 +/- 26% baseline, mean +/- SD) versus
      control (81 +/- 19%) and MK-801 (75 +/- 8%) (p = 0.030). Cerebral oxygen
      consumption recovered to 105 +/- 30% baseline in group MK-801 and 94 +/- 31% in
      control but only to 61 +/- 22% in group NBQX (p = 0.070). Cerebral blood flow
      stayed significantly lower in group NBQX relative to control. Thus, MK-801
      accelerates recovery of cerebral high-energy phosphates and metabolic rate after
      cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal.
      At the dosage used NBQX exerts an adverse effect.

PMID- 8263053
TI  - Effects of theophylline and cyclohexyladenosine on brain injury following normo-
      and hyperglycemic ischemia: a histopathologic study in the rat.
AB  - The present study was designed to determine the effects of theophylline, an
      adenosine receptor antagonist, and cyclohexyladenosine (CHA), an adenosine
      receptor agonist, on ischemic brain injury following normo- and hyperglycemic
      ischemia and reperfusion in fasted male Wistar rats. Moderate hyperglycemia was
      achieved by administering 17% D-glucose (3 g/kg i.p.), whereas normoglycemic
      animals received an equal volume of saline. The animals were further divided into
      two groups: One group was pretreated with either theophylline (0.20 mumol/g i.p.)
      or an equal volume of saline; the second group received either intraventricular
      CHA (6.25 nmol) or mock CSF prior to the onset of ischemia. During ischemia,
      pericranial temperature was maintained at 36 degrees C and EEG was monitored.
      Cerebral ischemia was induced for 15 min, after which flow was restored and the
      animals were allowed to recover completely. There were no significant differences
      in physiologic parameters among the groups studied. Five days following the
      ischemic episode, the rats were perfused with formalin and the brains subserially
      sectioned (8 microns) in the coronal plane and stained with celestine blue/acid
      fuchsin. Histopathologic analysis was performed in a blinded fashion to determine
      percentage of dead neurons. Hyperglycemic animals had significantly greater
      ischemic injury in CA1, cortex, and caudate than the normoglycemic group (p <
      0.01). Moreover, rats pretreated with theophylline had a significantly (p < 0.01)
      higher percentage of dead neurons in CA1, cortex, and caudate than corresponding
      controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263054
TI  - Photothrombotic infarction triggers multiple episodes of cortical spreading
      depression in distant brain regions.
AB  - The purposes of this study were to determine whether cortical spreading
      depression occurs outside of the infarct produced by photothrombotic vascular
      occlusion, and also the direction of spreading. Focal cerebral thrombotic
      infarction was produced by irradiating the exposed skull of anesthetized rats
      with green light (560 nm) following systemic injection of rose bengal dye. At
      proximal sites (approximately 2 mm anterior to the infarct border), transient,
      severe hyperemic episodes (THEs) lasting 1-2 min were intermittently recorded.
      THE frequency was greatest in the first hour and declined over a 3-h period. THEs
      were accompanied (and usually preceded) by a precipitous rise in [K+]0 (from
      approximately 3 to > 40 mM) and were associated with increases in local tissue
      oxygen tension (tPO2). Following the rise in [K+]0, clearance of [K+]0 to its pre
      THE baseline preceded baseline recovery of CBF. These data indicate that THEs
      were reactive to physiologic events resembling cortical spreading depression
      (CSD), which provoked increased demand for oxygen and blood flow, and which
      spread from proximal sites to areas more distal (approximately 4 mm) from the rim
      of the evolving infarct. MK-801 (1 mg/kg, i.v.) inhibited subsequent CSD-like
      episodes. We conclude that photothrombosis-induced ischemia provoked CSD which
      was triggered either within the infarct core or in the infarct rim and spread to
      more distal sites. Whether multiple episodes of CSD during infarct generation are
      responsible for the remote consequences of focal brain injury remains to be
      determined.

PMID- 8263055
TI  - Blood-brain barrier permeability and brain concentration of sodium, potassium,
      and chloride during focal ischemia.
AB  - Brain edema formation during the early stages of focal cerebral ischemia is
      associated with an increase in both sodium content and blood-brain barrier (BBB)
      sodium transport. The goals of this study were to determine whether chloride is
      the principal anion that accumulates in ischemic brain, how the rate of BBB
      transport of chloride compares with its rate of accumulation, and whether the
      stimulation seen in BBB sodium transport is also seen with other cations. Focal
      ischemia was produced by occlusion of the middle cerebral artery (MCAO) in
      anesthetized rats. Over the first 6 h after MCAO, the amount of brain water in
      the center of the ischemic cortex increased progressively at a rate of 0.15 +/-
      0.02 (SE) g/g dry wt/h. This was accompanied by a net increase in brain sodium
      (48 +/- 12 mumol/g dry wt/h) and a loss of potassium (34 +/- 7 mumol/g dry wt/h).
      The net rate of chloride accumulation (16 +/- 1 mumol/g dry wt/h) approximated
      the net rate of increase of cations. Three hours after MCAO, the BBB permeability
      to three ions (22Na, 36Cl, and 86Rb) and two passive permeability tracers
      ([3H]alpha-aminoisobutyric acid ([3H]AIB) and [14C]urea) was determined.
      Permeability to either passive tracer was not increased, indicating that the BBB
      was intact. The rate of 36Cl influx was 3 times greater and the rate of 22Na
      influx 1.8 times greater than their respective net rates of accumulation in
      ischemic brain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263056
TI  - Angiotensin II AT2 receptor stimulation extends the upper limit of cerebral blood
      flow autoregulation: agonist effects of CGP 42112 and PD 123319.
AB  - The effects of the angiotensin II AT2 receptor ligands CGP 42112 and PD 123319,
      the AT1 antagonist losartan, and the nonselective angiotensin II antagonist
      Sar1,Ile8-angiotensin II on the upper limit of CBF autoregulation were studied in
      pentobarbital-anesthetized rats. Blood pressure was increased by intravenous
      phenylephrine infusion, while CBF was measured continuously from the parietal
      cortex by laser-Doppler flowmetry. Intravenous infusions of CGP 42112 (0.1 and 1
      mg kg-1 min-1) and PD 123319 (0.36 and 1 mg kg-1 min-1) shifted the upper limit
      of CBF autoregulation toward higher blood pressures without affecting baseline
      CBF. Sar1,Ile8-angiotensin II (4 micrograms kg-1 min-1) had no effect on baseline
      CBF or CBF autoregulation but antagonized the effect of CGP 42112 and PD 123319.
      Losartan (10 mg/kg i.v. bolus) reduced baseline blood pressure and CBF and
      shifted the autoregulation curve toward higher blood pressures. Sar1,Ile8
      angiotensin II blocked the effect of losartan on baseline CBF but not on CBF
      autoregulation. These results suggest that both CGP 42112 and PD 123319 exert
      their effects on CBF autoregulation through stimulation of angiotensin II AT2
      receptors. The mechanism by which losartan affects CBF remains unclear.

PMID- 8263057
TI  - Reduced cerebral blood flow but intact reactivity to hypercarbia and hypoxia
      following subarachnoid hemorrhage in rabbits.
AB  - Subarachnoid hemorrhage (SAH) was produced in rabbits by four subarachnoid
      injections of blood (n = 7) or saline (n = 6); a control group (n = 6) had no
      injections. Basilar artery vasospasm was assessed by serial angiograms. Resting
      CBF (microspheres) and CBF reactivity to hypercapnia (65 and 85 mm Hg) and
      hypoxia (fractions of inspired oxygen of 0.15 and 0.10) were determined. Basilar
      artery vasospasm was seen with SAH. Resting CBF was reduced by 31% (SAH 43 +/-
      12, saline 65 +/- 17, control 60 +/- 21 ml 100 g-1 min-1), and resting
      cerebrovascular resistance was increased (SAH 1.84 +/- 0.30, saline 1.31 +/-
      0.49, control 1.39 +/- 0.25 mm Hg ml-1 100 g-1 min-1) after SAH. CBF rose to a
      similar degree in all three groups in response to hypercarbia and hypoxia. We
      conclude that resting CBF is reduced in this model of SAH, but vascular
      reactivity remains intact.

PMID- 8263058
TI  - Constriction/dilatation of the cerebral microvessels by intravascular endothelin
      1 in cats.
AB  - The effects of intracarotidly injected endothelin (ET)-1 (0.01-3 nmol) on the
      local cerebral blood volume (CBV) in the parietotemporal cortex were examined by
      the photoelectric method in 17 anesthetized cats. CBV reflects the cumulative
      dimensions of the cerebral microvessels. Low doses of ET-1 (0.01 and 0.1 nmol)
      elicited mild but significant reductions in CBV without changes in the systemic
      arterial blood pressure (SABP). High doses of ET-1 (3 nmol) initially induced
      marked declines of CBV, which were attributable to the significant falls in SABP.
      CBV subsequently exhibited significant increases. The CBV increases were not
      secondary to the accompanying elevations of SABP, since they were unaffected by
      inhibition of the SABP changes after preinjection of BQ-123 (1 mg/kg), an ET
      antagonist specific to the ETA receptors. The CBV increases, however, were
      prevented by continuous administration of NG-mono-methyl-L-arginine (0.35
      mg/kg/min), an inhibitor of nitric oxide synthesis, plus BQ-123. We conclude that
      while low doses of intravascular ET-1 constrict the cerebral microvessels, high
      doses of ET-1 dilate the cerebral microvessels through the induction of nitric
      oxide probably in the cerebrovascular endothelium.

PMID- 8263059
TI  - Magnetic resonance imaging of propagating waves of spreading depression in the
      anaesthetised rat.
AB  - Gradient echo magnetic resonance (MR) imaging was used to demonstrate propagating
      waves of cortical spreading depression (SD) in the anaesthetised rat. SD was
      initiated by remote perfusion with 150 mM KCl applied for 0.5-2 min to the left
      parietal cortex. Gradient echo MR images were obtained every 12-30 s in either a
      vertical coronal section or a horizontal section including the superficial cortex
      in plan view. Within 2 min of application of KCl, we observed a zone of increased
      signal intensity (3-15%) on the MR image, up to 2 mm across, lasting
      approximately 1 min and propagating away from the site of initiation. The mean
      velocity for 27 of such waves seen in seven animals was calculated to be 2.79
      mm/min, with means (+/- SD) in individual animals averaging 2.90 +/- 0.46 mm/min
      (n = 7). Increased signal intensity in gradient echo images has been attributed
      to an increased level of oxygenation within the venous blood. Our results are
      consistent with this interpretation although other physiological changes during
      SD may also contribute to the signal changes.

PMID- 8263060
TI  - Basic fibroblast growth factor dilates rat pial arterioles.
AB  - Basic fibroblast growth factor (bFGF) is a polypeptide that promotes the survival
      and differentiation of brain neurons, glia, and endothelial cells. It has been
      shown recently that intravenously administered bFGF lowers blood pressure by
      systemic vasodilation; this effect is mediated, in part, by nitric oxide (NO)
      dependent mechanisms. In the current study, we directly evaluated the effect of
      bFGF on pial arterioles of pentobarbital-anesthetized Sprague-Dawley rats (n =
      18) using the closed cranial window technique. Basic FGF (5-200 ng/ml) produced
      dose-dependent vasodilation; maximal vessel diameter (approximately 120% of
      control) was reached at 100 ng/ml. No vasodilation was found when bFGF was heat
      inactivated, or preincubated with blocking antibody. Moreover, bFGF-induced
      vasodilation was attenuated by coadministration of the NO synthase inhibitor NG
      nitro-L-arginine methyl ester (L-NAME), consistent with an NO-dependent
      mechanism. These results suggest that bFGF may play an important role in the
      regulation of cerebrovascular tone and cerebral blood flow.

PMID- 8263061
TI  - Intravital microreflectometry of individual pial vessels and capillary region of
      rat.
AB  - A microscopic reflectance spectrophotometer was constructed to obtain the spectra
      of single pial vessels and of a region containing only capillaries (capillary
      region). The difference in the oxygen saturation (SO2) of hemoglobin between the
      regional arteriole and venule [R(A - V)] and that between the regional arteriole
      or capillaries [R(A - C)] were calculated. The reduction of cytochrome aa3 was
      also estimated in the capillary region. This method was applied to the brain
      surface of spontaneously breathing rats subjected to hypoxic and anemic hypoxia.
      On decreasing the inhaled O2 from 100 to 15%, elevation of R(A - V) and R(A - C)
      with slight arteriolar dilatation (though statistically not significant) was
      observed. Below 10% O2 (especially at 4 and 3% O2), the R(A - V) and R(A - C)
      decreased in spite of significant arteriolar dilatation with progressive
      reduction of cytochrome aa3, indicating suppression of oxygen transport to
      mitochondria. In the case of hemodilution down to 37% hematocrit (Ht), elevation
      of R(A - V) and R(A - C) occurred with a slight tendency toward arteriolar
      dilatation. Below 32% Ht, the R(A - V) decreased but the R(A - C) remained
      steady, while reduction of cytochrome aa3 progressed. Altogether, the SO2 in the
      capillary region decreased and the reduction of cytochrome aa3 progressed with
      the decline of arteriolar O2 supply in both hypoxic and anemic hypoxia.

PMID- 8263062
TI  - [11C]tropanyl benzilate-binding to muscarinic cholinergic receptors: methodology
      and kinetic modeling alternatives.
AB  - Quantitative estimation of cerebral muscarinic receptors was investigated with
      the use of the antagonist [11C]tropanyl benzilate ([11C]TRB) and positron
      emission tomography (PET). Kinetic modeling alternatives were examined with the
      goal of identifying an analysis method providing stable receptor measures, yet
      avoiding biases from inappropriate reductions in model complexity. Dynamic PET
      scans were performed on six young normal volunteers. Several modeling approaches
      yielding relative receptor density measures were evaluated: (a) a single "late"
      scan using relative tracer concentration values; (b) a slope estimate from
      graphic analysis (Patlak plot); (c) a two-compartment, two-parameter model
      (transport and total ligand distribution volume); (d) a three-compartment, two
      parameter model using the free+nonspecific distribution volume, DV', fixed to the
      cerebellar value; (e) an early scan for transport, a fixed value for DV', and a
      single late scan for the binding rate constant; and (f) a three-compartment,
      three-parameter model. Both computer simulations and PET scan results indicate
      all methods provide receptor density index measures with the same rank order as
      in vitro measures. Oversimplified approaches (methods 1 and 2) yield a more
      highly nonlinear relation between the estimated receptor density index and the
      known receptor density than do methods retaining greater model complexity
      (methods 3-6). However, noise propagation into the receptor measure is greater
      for the more complex methods. Reliable receptor density information can be
      obtained from kinetic [11C]TRB PET studies, with methods 3-5 providing the most
      appropriate levels of model complexity for estimates of relative muscarinic
      receptor density.

PMID- 8263063
TI  - Characterization of 99mTc-bicisate as an agent for the measurement of cerebral
      blood flow with SPECT.

PMID- 8263064
TI  - Regional cerebral blood flow imaging with 99mTc-bicisate SPECT in asymmetric
      Parkinson's disease: studies with and without chronic drug therapy.
AB  - Regional cerebral perfusion was assessed in six patients with asymmetric
      Parkinson's disease (PD) of mild to moderate severity and in six matched normal
      subjects using 99mTc-bicisate single photon emission computed tomography (SPECT).
      Regional activity was normalized to whole-brain activity. Each subject was
      studied twice, separated by 15.2 +/- 9.2 and 18.0 +/- 4.8 days in normals and PD
      patients, respectively. There was low intrasubject scan-rescan variability in
      normals, with all regions showing an average intrasubject difference in repeat
      studies of < 3%. In PD patients after chronic oral antiparkinsonian drugs had
      been withdrawn, as compared with normal subjects, there was increased perfusion
      in the caudate and lenticular nuclei contralateral to the worst affected
      extremities. This increased basal ganglia perfusion was attenuated by chronic
      oral therapy. The clinical relevance of these changes is indicated by the high
      positive correlation between various measures of clinical PD severity and the
      lenticular perfusion. These differences in basal ganglia perfusion measured with
      99mTc-bicisate SPECT in mild to moderate, asymmetric PD may be secondary to
      increased metabolic demand resulting from alterations of synaptic activity.

PMID- 8263065
TI  - Use of 99mTc-bicisate in activation studies by split-dose technique.
AB  - The properties of the brain single photon emission computed tomography (SPECT)
      tracer 99mTc-bicisate (ethyl cysteinate dimer) were examined in regard to its use
      in test-retest studies with short-interval, split-dose studies. The stimulus
      applied in these tests was a visual activation by a "flickering chessboard"
      pattern. We used a fast dynamic SPECT (Tomomatic 232) recording eight slices.
      Twelve volunteers were assigned to two groups for reproducibility control and
      stimulation experiments, respectively. All were examined on 2 days. On the first
      day, only one injection was given in the resting state (t = 0), while two
      recordings were performed (t = 30 and t = 100), simulating the course and timing
      of a full split-dose study. The average washout of 8.3 +/- 1.0% was used as a
      correction on the second-day study. On that day the first injection was given
      during rest exactly as on day 1, allowing an estimate of day-to-day
      reproducibility. The second injection was made either in a resting state
      identical to the first or during visual stimulation. All images were normalized
      to mean brain count value. Results were analyzed in predefined anatomical regions
      of interest (ROIs). The day-to-day reproducibility was fair, with only one ROI
      (inferior frontal cortex) showing a significant 2% decrease. The studies of day 1
      revealed a regional difference in observed washout ranging in the applied
      cortical ROIs from 7.9 to 11.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263066
TI  - Brain extraction and distribution of 99mTc-bicisate in humans and in rats.
AB  - Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L-cystein
      diethylester (bicisate, ECD) was measured repeatedly in five patients by means of
      the intravenous (i.v.) double-indicator technique using 24Na+ as an intravascular
      cotracer. After i.v. injection, the arterial concentration curve of 99mTc
      bicisate was delayed and dispersed compared with that of the intravascular
      cotracer, presumably due to lung retention of the flow tracer. The corrected
      cerebral venous output curves were fitted using a three-compartment model with
      four parameters. At resting cerebral blood flow (CBF) values, the unidirectional
      brain extraction was 0.57 +/- 0.05, the permeability-surface area product for
      passage from blood to brain (PS1) was 0.48 +/- 0.07 ml/g/min, and the
      distribution volume for bicisate was 0.74 +/- 0.20 (mean +/- SD). In a single
      patient, BBB transport after i.v. injection of bicisate was compared with that of
      a similar flow tracer, d,l-hexamethylpropyleneamine oxime (HM-PAO), and similar
      values were found for the two tracers. In 19 rats, the brain extraction of
      bicisate was measured by means of the intracarotid double-indicator technique.
      The brain extraction was measured at resting, decreased, and increased CBF
      values. Low CBF values were obtained by hyperventilation and high values by
      hypercapnia. The degree of backflux of tracer from brain to blood was evaluated
      by means of the three-compartment model and was found to be negligible in these
      experiments. The brain extraction was 0.70 +/- 0.1 and PS1 was 0.94 +/- 0.27
      ml/g/min. During hypercapnia, CBF increased from 0.77 to 1.09 ml/g/min, leading
      to a significant decrease in brain extraction, from 0.70 to 0.56.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8263067
TI  - Retention of 99mTc-bicisate in the human brain after intracarotid injection.
AB  - 99mTc-bicisate (ECD) was injected as a bolus into the internal carotid artery,
      and cerebral uptake and retention were recorded with fast-rotating single photon
      emission computed tomography (SPECT) equipment in four patients suffering from
      temporal lobe epilepsy. Quantitative regional cerebral blood flow (rCBF) was
      measured tomographically with the 133Xe inhalation technique. We applied a three
      compartment kinetic model and algorithms modified from a previous analysis of
      99mTc d,l-hexamethylpropyleneamine oxide (HM-PAO) kinetics. The bicisate brain
      uptake and retention curve was very similar to that of HM-PAO, and it can be
      described by a triexponential function including an initial steep component
      representing the vascular transmitted spike, a second less steep component
      representing back-diffusion from brain tissue to blood, and a third, very slow
      component, representing the very slow loss due to incomplete retention of the
      deesterified hydrophilic metabolites. Computerized curve-fitting on data from
      three patients gave average kinetic values for the first-passage (unilateral)
      extraction of E = 0.60 (range, 0.59-0.61); the overall retained fraction of the
      tracer supplied was R = 0.44 (0.43-0.45), and the conversion/clearance ratio was
      alpha = k3/k2 = 2.59 (2.38-2.77). This alpha is higher than that for HM-PAO, and
      therefore bicisate uptake as a function of blood flow is more linear than in HM
      PAO. Less correction for backdiffusion is therefore needed. From 1 to 24 h there
      was an average loss of hydrophilic tracer of 3.5%/h, but the late distribution
      images were essentially unchanged over time, pointing to practically the same
      rate of loss in all regions.

PMID- 8263068
TI  - Quantitation of brain perfusion with 99mTc-bicisate and single SPECT scan:
      comparison with microsphere measurements.
AB  - This study describes and validates in a preliminary manner a method to measure
      the steady-state influx constant (Ki) of 99mTc-bicisate with one single photon
      emission computed tomography (SPECT) scan. The method is based on the analysis of
      the arterial concentration of the radioactivity. The results of this quantitation
      procedure were compared with regional CBF (rCBF) measurements made using 99mTc
      microspheres (MI). Two quantitative indexes of perfusion, fractional brain uptake
      (FBU) and normalized (with cerebellum) brain uptake (NBU), were also evaluated.
      Two SPECT studies were performed on seven cardiovascular patients who had no
      signs of neurological disease. In the first of these, 99mTc-bicisate was used,
      while in the other, which was performed 2 days later, MI were injected into the
      left heart ventricle. The values of the FBU, NBU, and Ki of 99mTc-bicisate were
      calculated in several gray and white matter brain regions of interest (ROIs) and
      compared with the rCBF values measured with MI in coupled ROIs. Mean FBU values
      were 0.00008 +/- 0.00002 and 0.00004 +/- 0.00001 in the gray and the white
      matter, respectively. Mean NBU values were 0.99 +/- 0.04 and 0.54 +/- 0.05, mean
      Ki values were 0.36 +/- 0.06 and 0.19 +/- 0.03 ml g-1 min-1 and mean rCBF values
      were 0.51 +/- 0.04 and 0.27 +/- 0.04 ml g-1 min-1 in gray and white matter,
      respectively. Analysis of variance of the regression gave different F values for
      the regressions with rCBF of FBU (F = 19, n = 126), NBU (F = 289, n = 112), and
      Ki (F = 117, n = 126).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263070
TI  - Studies of the retention mechanism of the brain perfusion imaging agent 99mTc
      bicisate (99mTc-ECD).
AB  - The structure-activity relationship in a series of analogues of 99mTc-bicisate
      (99mTc-N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester dihydrochloride, RP-217)
      is described using in vivo studies in rodent and primate models and in vitro
      studies in rodent and primate brain tissue. All analogues investigated were 99mTc
      diamine dithiol diesters, which were neutral and lipophilic and had modified
      brain uptake indexes (> or = 40) suggesting adequate first-pass extraction. All
      analogues were poorly retained by the rodent brain. In contrast, the
      stereochemistry and structure of the 99mTc-complexes affected their brain
      retention in primates. All compounds that demonstrated selective primate brain
      retention were L-diesters that were metabolized in primate brain tissue to
      nonlypophilic complexes resulting from ester hydrolysis. Unretained complexes
      were not metabolized in primate brain tissue. More extensive studies were
      performed with 99mTc-bicisate, which demonstrated poor brain retention in several
      nonprimate species (i.e., dogs, ferrets, pigs, and rodents). In rodent and
      nonhuman primate tissue, 99mTc-bicisate was rapidly metabolized to a monoacid
      ester (99mTc-N,N'-1,2-ethylenediylbis-L-cysteine monoethyl ester). Therefore,
      brain metabolism of 99mTc-bicisate results in the formation of an acid product(s)
      that is selectively trapped in primate brain.

PMID- 8263069
TI  - Correlation between 99mTc-bicisate and regional CBF measured with iodo
      [14C]antipyrine in a primate focal ischemia model.
AB  - The need for an agent to quantitatively measure regional cerebral blood flow in
      humans using single photon emission computed tomography has led to the
      development of a new 99mTc-labeled agent: bicisate (ethyl cysteinate dimer). We
      have utilized an acute stroke model in the baboon to examine the ability of this
      agent to quantitatively measure regional cerebral blood flow in ischemic tissue.
      One hour after occlusion of either the left anterior cerebral or the middle
      cerebral artery, 99mTc-bicisate was administered intravenously, followed 20 min
      later by the measurement of local cerebral blood flow using iodo-[14C]antipyrine.
      With use of double-label autoradiography, the distribution of 99mTc-bicisate was
      correlated with the local cerebral blood flow images. A cerebral blood flow
      parameter was calculated from the 99mTc-bicisate tissue distribution and the
      arterial blood tracer concentration using an indicator fractionation model. For
      cerebral blood flows above approximately 40-50 ml 100 g-1 min-1, 99mTc-bicisate
      underestimates cerebral blood flow by as much as 20%, while for blood flows below
      approximately 15 ml 100 g-1 min-1, blood flow is overestimated by the 99mTc
      bicisate distribution by an average of 3-4 ml 100 g-1 min-1. This apparent
      hyperfixation at very low blood flows may be related to a higher extraction of
      this tracer by ischemic tissue.

PMID- 8263071
TI  - 99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show
      reflow hyperemia in subacute stroke: report of a multicenter trial of 105 cases
      comparing 133Xe and 99mTc-bicisate (ECD, neurolite) measured by SPECT on same
      day.
AB  - A multicenter study was performed in seven European centers comparing 99mTc
      bicisate with 133Xe as a means of evaluating bicisate as a tracer of CBF
      distribution in humans. The same type of single photon emission computed
      tomography (SPECT) instrument (Tomomatic) was used in all centers. A total of 115
      cases were collected, and of these 105 were considered technically adequate,
      comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain
      tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave
      better spatial resolution than Xe. Agreement between the results of the two
      methods was noted in 98 cases, but not in the remaining 7, all belonging to the
      stroke group. These seven all suffered from a subacute stroke (11-23 days after
      onset), and the disagreement in all cases consisted of bicisate showing low count
      rate in the area of the infarct and Xe a normal or elevated flow (luxury
      perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these
      seven cases comprised all the reperfusion cases in the series. The results
      validate bicisate as a tracer of CBF in normal humans and in chronic brain
      diseases. Only in a subgroup of subacute stroke cases does bicisate not follow
      CBF, as it fails to show reperfusion hyperemia. This suggests the usefulness of
      bicisate in stroke cases, particularly in the subacute phase, where other SPECT
      methods often present difficulties due to reflow masking the size and the
      severity of the lesion.

PMID- 8263072
TI  - Assessment of postischemic reperfusion and diamox activation test in stroke using
      99mTc-ECD SPECT.
AB  - To evaluate the cerebral distribution of 99mTc-ethyl cysteinate dimer (99mTc-ECD)
      at blood flow levels beyond the normal range, we investigated postischemic
      reperfusion and acetazolamide (Diamox) activation test in stroke patients. The
      postischemic reperfusion was studied in 10 patients who showed a postischemic
      hyperperfusion area on other single photon emission computed tomography (SPECT)
      studies using N-isopropyl-rho-[123I]iodoamphetamine ([123I]IMP), 99mTc-hexamethyl
      propyleneamine oxime (99mTc-HMPAO), or 133Xe. 99mTc-ECD SPECT demonstrated a
      hyperactive area in one case, an isoactive area in four, and a hypoactive area in
      five. Correlations with CT findings revealed hyperactive areas without any
      abnormality, isoactive areas with perifocal rim, perifocal edema, or diffuse
      cerebral edema, and hypoactive areas with an infarct core. The Diamox activation
      test was studied in eight other patients with atherothrombotic stroke, and a
      limitation in vasodilative capacity was classified into three grades: Gr. 0 (none
      to minimal), Gr. I (mild), and Gr. II (moderate). [123I]IMP SPECT showed Gr. II
      and limitation in all eight cases. However, 99mTc-ECD showed Gr. II in three
      cases and Gr. I in five, and 99mTc-HMPAO revealed Gr. II in two cases, Gr. I in
      three, and Gr. 0 in three. We suggest that a lack of retention of 99mTc-ECD in a
      postischemic reperfusion area indicates the severity of the initial brain damage.
      Although the limitation in vasodilative capacity under Diamox-activated
      conditions was underestimated using 99mTc-labeled CBF tracers as compared with
      [123I]IMP, a retention of 99mTc-ECD in the unaffected area with an increased CBF
      under Diamox activation could be relatively superior to 99mTc-HMPAO.

PMID- 8263073
TI  - Brain perfusion SPECT with 99mTc-bicisate: comparison with PET measurement and
      linearization based on permeability-surface area product model.
AB  - To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate,
      single photon emission computed tomography (SPECT) images of 99mTc-bicisate were
      compared with CBF images obtained by positron emission tomography (PET) using the
      15O steady-state method in 10 cases of cerebrovascular disease and dementia.
      99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern
      except for two cases with subacute stroke, in which 99mTc-bicisate showed less
      uptake than CBF in the infarcted area where oxygen metabolism was severely
      diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases
      showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT.
      Although the SPECT count ratio of cerebral structures to cerebellum showed a good
      correlation with CBF ratio, it gradually deviated from the linear relationship in
      the high-flow range. Assuming this nonlinear relationship is due to the limited
      extraction of the tracer, we estimated the permeability-surface area product (PS)
      value by a nonlinear least-squares curve-fitting procedure. The correction of the
      nonlinear relationship using the estimated PS value and a table lookup method
      resulted in an excellent linear relationship between corrected SPECT counts and
      CBF.

PMID- 8263074
TI  - Cerebral uptake of 99mTc-bicisate in patients with cerebrovascular disease in
      comparison with CBF and CMRO2 measured by positron emission tomography.
AB  - The regional brain uptake of 99mTc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethyl
      ester (99mTc-bicisate) measured by single photon emission computed tomography
      (SPECT) was compared with the regional CBF and CMRO2 measured by positron
      emission tomography in patients with cerebrovascular disease. Nine patients with
      the diagnosis of cerebral ischemic disorders (n = 7) or cerebral hemorrhage (n =
      2) were studied. 99mTc-Bicisate brain uptake correlated with CBF and CMRO2.
      However, 99mTc-bicisate uptake did not reflect CBF in the single lesion showing
      luxury perfusion, which seemed to resemble a CMRO2 image. Though quantitative
      analysis showed the nonlinear correspondence of 99mTc-bicisate brain uptake with
      CBF and CMRO2, this correspondence could be corrected into a more linear
      relationship using a correction factor. 99mTc-Bicisate washout from the brain had
      no correlation to CBF and CMRO2. This diffuse decreasing washout rate was
      approximately 15% during the first hour after injection. By using the lipophilic
      fraction of arterial blood and a linearized correction of 99mTc-bicisate SPECT
      images, the feasibility of obtaining a factor-related CBF and CMRO2 was suggested
      from our data. These results suggested that 99mTc-bicisate had good
      characteristics for routine clinical use with SPECT to display the brain function
      in patients with neurological disorders.

PMID- 8263075
TI  - Regional cerebral blood flow imaging: a quantitative comparison of 99mTc-bicisate
      with 133Xe using single photon emission computed tomography.
AB  - The aim of this study was to compare 99mTc-bicisate with 133Xe inhalation in
      regional CBF (rCBF) imaging. Five healthy volunteers and five patients were
      imaged with both techniques. Regional standardized values (SVs) of 99mTc
      bicisate, uptake indexes (UIs), and asymmetry indexes (AIs) were compared
      quantitatively with, respectively, rCBF, flow indexes (FIs), and AIs. Areas with
      highest rCBF (sylvian and thalamic areas) appeared to be underestimated with
      99mTc-bicisate, but significant correlations were found between SV and rCBF (n =
      140, r = 0.468, p < 0.01) and for the 10 subjects between UI and FI and between
      AIs (p < 0.0001). There are therefore distinct regional differences in the
      cerebral distinction of 99mTc-bicisate and CBF, particularly in the thalamus and
      the temporal cortex. It is probable but not yet proved that an underestimation of
      high flow rates occurs with bicisate.

PMID- 8263076
TI  - Comparison of brain SPECT using 99mTc-bicisate (L,L-ECD) and [123I]IMP in
      cortical and subcortical strokes.
AB  - Single photon emission computed tomography (SPECT) using 99mTc-bicisate and N
      isopropyl-p-[123I]iodoamphetamine ([123I]IMP) was compared in 25 patients
      suffering cerebral ischemia during the subacute phase (7-14 days) of stroke.
      Patients were classified as cortical strokes (15) and subcortical strokes (10)
      according to clinical and CT data. Images were analyzed by five independent
      blinded observers. Then, using a cross-matching method between normal and
      abnormal brain areas, we evaluated the sensitivity and specificity for 99mTc
      bicisate and [123I]IMP and inter- and intraobserver reproducibility. A
      semiquantitative analysis was performed to compare abnormal hypoactive areas
      versus the corresponding contralateral areas for 99mTc-bicisate and [123I]IMP in
      the two patient groups. There was no significant difference for sensitivity and
      specificity between 99mTc-bicisate and [123I]IMP. Matching was approximately 90%
      in the two groups. The kappa-concordance index was satisfactory and slightly
      better for 99mTc-bicisate (0.485) than for [123I]IMP (0.435). Level of
      hypoactivity in the abnormal areas was significantly higher for 99mTc-bicisate (p
      < 0.03, n = 25) than for [123I]IMP, especially for cortical strokes. This
      comparative study demonstrates that 99mTc-bicisate is a very useful tracer for
      the detection of focal cerebral ischemia by SPECT during the subacute phase of
      stroke.

PMID- 8263077
TI  - The role of single photon emission computed tomography brain imaging with 99mTc
      bicisate in the localization and definition of mechanism of ischemic stroke.
AB  - 99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from
      a radiochemically stable kit (Neurolite). A multicenter trial was conducted to
      determine the sensitivity and specificity of single photon emission computed
      tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic
      stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls.
      Imaging results from 148 subjects (107 stroke patients and 41 controls) were
      considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc
      bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was
      compared with a final assessment using all clinical, diagnostic, and laboratory
      procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and
      well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of
      98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95%
      confidence interval, 0.64-0.86). Results were unchanged over time and were
      similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%).
      In a secondary analysis, a normal image or small, deep (e.g., subcortical)
      perfusion defect was highly predictive of a lacunar mechanism. Defects involving
      the cortical surface were strongly associated with nonlacunar mechanisms. SPECT
      imaging with 99mTc-bicisate is a sensitive marker in the localization of
      perfusion defects associated with ischemic stroke and may assist in the
      determination of the underlying mechanism of a stroke.

PMID- 8263078
TI  - 99mTc-bicisate (neurolite) SPECT brain imaging and cognitive impairment in
      dementia of the Alzheimer type: a blinded read of image sets from a multicenter
      SPECT trial.
AB  - A blinded read of images obtained with 99mTc-bicisate and single photon emission
      computed tomography (SPECT) was conducted to determine if a relationship exists
      between the severity of abnormalities on SPECT brain images and the severity of
      cognitive impairment in patients with dementia of the Alzheimer type (DAT) and to
      examine the interreader agreement for visual reading of images in a multicenter
      SPECT study. Images for a total of 86 subjects were available for the blinded
      read. The images for 28 subjects were rated as noninterpretable due to technical
      inadequacies. Images for 58 subjects (45 DAT patients and 13 normal volunteers)
      from 10 SPECT centers were selected for further analyses. The severity of
      abnormality was rated as mild, moderate, or severe by three readers. In DAT
      patients, a significant negative correlation (p < 0.05) of Mini-Mental State
      Examination (MMSE) score with global severity of abnormality was noted for two of
      the three readers. A significant correlation (p < 0.05) between MMSE score and
      severity of abnormality was observed for all three readers for the posterior
      temporoparietal region. The blinded readers rated a median of 92.3% of normal
      volunteers' images as normal and a median of 82.2% of DAT patients' images as
      abnormal. For the regional severity of abnormality, the median percentage
      interrater agreement across all regions ranged from 95 to 100% in normal
      volunteers and from 81 to 98% in DAT patients. These results suggest that SPECT
      brain imaging with 99mTc-bicisate provides functional information about the
      severity of cognitive impairment in DAT patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263079
TI  - Spirituality and risk: toward an understanding.
AB  - To be fully healthy is to risk encountering and embracing the complex substrate
      of mysterious life-giving and life-denying spiritual forces, the hidden wholeness
      of God. Risky health behavior may paradoxically arise from the psychospiritual
      need to both probe and avoid probing the deeper understandings of health
      reflected in the tensions between good and evil. Avoidance of the painful truths
      of poverty, racism, sexism, and classism among other evils in our society results
      in the prevalence of high-risk life styles, addictions, and violent behaviors.
      Spiritual paradigms from holistic community care are needed to enable communities
      to more fully respond to the health empowering potential of the hidden wholeness
      rather than hiding from it.

PMID- 8263080
TI  - Community health nursing in the 1990s--risky business?
AB  - The atmosphere in which community health nurses (CHNs) work in city, suburban,
      and rural neighborhoods has become increasingly dangerous. Using Neuman's Systems
      Theory, four graduate students surveyed CHNs from three certified home health
      agencies to ascertain the real and perceived safety risks which these workers
      face daily. The response from all three agencies was similar as the nurses
      identified several situations in which they felt that their safety was
      compromised. As a result of the information gathered, a Community Risk-Reduction
      Plan was formulated.

PMID- 8263081
TI  - Business risk and the health care entrepreneur.
AB  - This article addresses issues of business risk in the home health care industry.
      General concepts of risk are discussed, and the unique attributes affecting risk
      in the home health industry are identified and reviewed particularly as they
      affect market entry strategies, differentiation, innovation, and regulation.

PMID- 8263082
TI  - When third party payment determines service: the elderly at risk.
AB  - Third party reimbursement policies have created barriers to coordinated health
      services. They have had the effect of compromising the nature and quality of the
      delivery of nursing service to the elderly in the home setting, thereby posing
      health risks to older adults. The practice of holistic nursing requires a total
      commitment to the advocacy role in order to reduce risks to elderly clients and
      to provide them with quality care.

PMID- 8263083
TI  - Use of alternative health therapies by people with multiple sclerosis: an
      exploratory study.
AB  - Sixteen people with multiple sclerosis (MS) responded to a semi-structured
      questionnaire about their experiences with alternative therapies. No definition
      of alternative therapies was provided. Physical therapy, counseling, nutrition,
      and massage were the most frequently used alternative therapies. Other therapies
      included acupuncture, occupational therapy, aquatic therapy, Therapeutic Touch,
      yoga, passive exercise, and removal of mercury alloy tooth fillings. Almost two
      thirds of the respondents reported seeking an alternative health practitioner
      because traditional physicians offered no cure for MS. Just under one third of
      the respondents stated that the quality of their lives was improved by
      alternative therapies.

PMID- 8263084
TI  - Risk taking: nursing's comfort zone.
AB  - Pressure to assume increasing risks, both individually and organizationally, has
      become a bellwether for nursing's practitioners, managers, and educators.
      Inherent in the role of today's nurse is the ability to make decisions, often
      with risk, at both an individual and a collective level. Yet, until recently,
      nursing's ability to practice independent decision making for both their clients
      and policies governing their practice were neither supported nor endorsed. The
      literature indicates a significant number of nurses value risk taking and are
      willing to make informed decisions regarding the probability of rewards and the
      consequences associated with failure. How and when these risks are assumed is
      dependent upon a variety of influences.

PMID- 8263085
TI  - Risk and reality for nurse educators.
AB  - To maintain the present cadre of nurse educators the paradoxes that put them at
      risk must be addressed. Three major paradoxical issues are explored: the
      persistent focus on the vocational model as vehicle for the development of the
      professional nurse, hindrances to anticipatory and incumbency socialization, and
      tenure and promotion requirements. Greater socialization and better educational
      academic preparation will increase the success and satisfaction of nursing
      faculty.

PMID- 8263086
TI  - The effects of guided imagery on anxiety levels and movement of clients
      undergoing magnetic resonance imaging.
AB  - This randomized, experimental study examined the effects of guided imagery on
      anxiety levels and on movement of clients undergoing nonemergency magnetic
      resonance imaging (MRI). Subjects who listened to a guided imagery/relaxation
      tape (n = 20) before their MRI scan and used guided imagery during their scan had
      lower levels of state anxiety than the control group (n = 21). Based on subject
      report and operator report, the experimental group moved less frequently during
      the MRI than the control group. The results of this investigation support the use
      of guided imagery as a therapeutic intervention and Rogers' Science of Unitary
      Human Beings.

PMID- 8263087
TI  - When cultural practices are health risks: the dilemma of female circumcision.
AB  - The circumcision of young women and girls is widespread in African countries as
      well as in other parts of the world and clearly places them at risk for serious
      health consequences. Plans to eradicate the practice must recognize the cultural
      underpinnings that have maintained it. This article discusses the types of female
      circumcision and the concomitant short- and long-term health risks. The cultural
      aspects and origins of the procedure are described and a simple model of risk
      taking based on control, information, and time is used to explain the complexity
      of issues that may be involved in the decision of women to consent to the
      procedure.

PMID- 8263088
TI  - "But I know my man!" HIV/AIDS risk appraisals and heuristical reasoning patterns
      among childbearing women.
AB  - This exploratory study examined HIV/AIDS risk appraisals, life-style choices, and
      heuristical reasoning patterns reported by 105 urban childbearing women. The
      availability heuristic was the strategy most frequently described by participants
      to distance themselves from the risks of having or getting HIV/AIDS within the
      social and communal context of their lives. The findings suggest that objective
      (provider) and subjective (client) interpretations of HIV/AIDS risks should be
      incorporated into pragmatic prevention programs initiated by nurses. The data
      further suggest that such urban childbearing women must be involved in ongoing
      HIV/AIDS prevention and early-intervention initiatives throughout their
      reproductive lives.

PMID- 8263089
TI  - The risk of not understanding nursing history.
AB  - Studying nursing history allows nurses to understand more fully problems
      currently affecting the profession, such as pay, regulation, shortage, education,
      defining practice, autonomy, and unity. Present day nurses cannot effectively
      address these important issues without a foundation of historical knowledge. In
      short, examining history allows nurses to more fully appreciate their important
      role in the health care system of the United States. This appreciation can
      provide nurses with important political strength.

PMID- 8263090
TI  - Column-switching techniques for high-performance liquid chromatography of drugs
      in biological samples.
AB  - In recent years, an increasing number of publications have demonstrated the
      potential of column-switching techniques for the chromatographic separation,
      determination and preparative isolation of analytes from biological matrices.
      Column-switching systems greatly facilitate drug analysis, by on-line sample
      clean-up and trace enrichment, or by improving the analytical separative process.
      In this paper, the main applications of column-switching techniques to drug
      analysis in biological samples, are reviewed.

PMID- 8263091
TI  - Two-dimensional high-performance liquid chromatographic method for assaying S
      adenosyl-L-methionine and its related metabolites in tissues.
AB  - S-Adenosyl-L-methionine (SAM) is a methyl-donor compound which is actively
      involved in a variety of biochemical reactions. An assay has been developed
      permitting the quantitative measurement of SAM and its related metabolites (S
      adenosylhomocysteine, decarboxylated SAM, methylthioadenosine, adenosine and
      adenine) in liver and cell cultures. As gradient reversed-phase chromatographic
      or cation-exchange chromatographic methods often resulted in overlapping peaks, a
      two-dimensional high-performance liquid chromatographic (HPLC) procedure was
      developed involving gradient reversed-phase chromatographic separation followed
      by ion-exchange chromatography. After precipitating large molecules in the sample
      by perchloric acid, gel permeation was carried out on a Sephadex G 25 column to
      separate small water-soluble metabolites from proteins and membrane fragments.
      The freeze-dried sample was injected onto an ODS column and a 0-10% acetonitrile
      gradient in 10 mM ammonium formate buffer (pH 2.9) (20 min, linear) was applied.
      The relevant fractions were collected and injected onto a cation-exchange column
      (Partisil SCX, 10 microns, 250 mm x 4.6 mm I.D.). Elution and quantification were
      carried out using ammonium formate buffers of various concentration (15-400 mM),
      pH 2.9. The detector response (254 nm) as a function of concentration was linear
      over the concentration range 30-500 pmol. The detection limits of the compounds
      after the two-dimensional chromatographic procedure ranged from 10 to 60 pmol and
      the recovery was higher than 70%. The reproducibility of the results obtained
      from given samples was within 9-22% for rat liver and 6-24% for mast cells.

PMID- 8263092
TI  - Determination of zinc-65, copper-64 and sulphur-35 labelled rat hepatoma tissue
      culture metallothioneins by high-performance liquid chromatography with on-line
      radioactivity detection.
AB  - Molecular size exclusion (MSE), reversed-phase (RP), and anion-exchange (AE) high
      performance liquid chromatography (HPLC) techniques were employed in combination
      with on-line radioactivity detection, in a study on the kinetic behaviour of 65Zn
      , 64Cu- and [35S]cysteine-labelled metallothionein (MT) in rat hepatoma tissue
      culture (HTC) cells. MSE-HPLC of [35S]cysteine-labelled HTC cell cytosol resulted
      in co-eluting MT-I and MT-II isoforms (tR 19.80 min; Ve/Vo: 1.85). AE-HPLC of
      65Zn-treated HTC cell cytosol yielded separated 65Zn MT-I (tR 11.5 min; I = 64
      mM) and 65Zn MT-II (tR 14.5 min; I = 104 mM). RP-HPLC of 64Cu-treated HTC cytosol
      resulted in separated 64Cu MT-I (tR 26.4 min) and 64Cu MT-II (tR 23.4 min).
      Determination of the amino acid composition, apparent molecular mass and cysteine
      content of HTC MT-I and MT-II isoforms showed the characteristics of class I
      metallothioneins. The rate of dissociation of Zn2+ from Zn-MT could be determined
      from the losses of 65Zn from MT during a single AE-HPLC run, showing a Zn-MT
      dissociation half-life of 0.66 h. RP-HPLC showed a delay in incorporation of
      newly accumulated 64Cu into MT, possibly owing to the appearance of reduced
      glutathione as an intracellular copper-transfer compound. Application of
      compartmental analysis in [35S]-cysteine accumulation experiments permitted the
      determination of the actual rate of MT degradation; when 200 microM of Zn were
      applied, the MT degradation half-life was 2.0 +/- 0.8 h. These results indicate
      the potential of combined HPLC techniques and application of radionuclides in
      studies on the synthesis and degradation of MT and metal-MT complexes.

PMID- 8263093
TI  - Solid-phase extraction and gas chromatographic-mass spectrometric determination
      after hydrolysis of 2-aminofluorene haemoglobin adducts in blood of rats.
AB  - 2-Nitrofluorene is an environmental pollutant that binds covalently to
      haemoglobin after nitroreduction and successive N-hydroxylation. these
      haemoglobin adducts can be cleaved in vitro by mild base-catalysed hydrolysis.
      For the enrichment of arylamines from the aqueous hydrolysate, an extraction
      procedure with an organic solvent is widely used. Because of the formation of a
      thick emulsion layer between the aqueous and organic solvent layers, the
      extraction is laborious and inefficient. The use of Amberlite XAD2 provides a
      simple extraction procedure yielding a recovery of ca. 70%. Calibration curves in
      haemoglobin solution were prepared with a correlation coefficient of 0.998 (n =
      12). The inter-day coefficient of variation amounted to 14%.

PMID- 8263094
TI  - Determination of acrylamide in rat serum and sciatic nerve by gas chromatography
      electron-capture detection.
AB  - A modified method for the derivatization and determination of acrylamide as 2
      bromopropenamide by gas chromatography-electron-capture detection was developed
      and applied to serum and sciatic nerve from rats. The method was accurate and
      precise over the calibration range 2.24-7.47 micrograms/ml in serum diluted 1:125
      and 4-122 micrograms/g in sciatic nerve homogenate (5 mg/ml). limits of detection
      were estimated to be 1200 ng/ml in undiluted serum and 3 micrograms/g in intact
      sciatic nerve. The use of less dilute samples to allow for lower limits of
      detection appears feasible. The time-course of acrylamide in serum and sciatic
      nerve was studied after acute dosing and indicated elimination half-lives of 1.8
      and 2.0 h for serum and sciatic nerve, respectively. A dose-effect relationship
      was established for each matrix after acute dosing and the measured acrylamide
      concentrations in serum (microgram/ml) were approximately the same as in sciatic
      nerve (microgram/g).

PMID- 8263095
TI  - Gas chromatographic-mass spectrometric screening procedure for the identification
      of formaldehyde-derived tetrahydroisoquinolines in human urine.
AB  - A gas chromatographic-mass spectrometric method has been developed for the
      identification of 1,2,3,4-tetrahydroisoquinoline and six metabolites extracted
      from urine in the picogram range. The derivatization procedure for the
      substances, formed by reaction of formaldehyde with biogenic amines, employs
      propionic anhydride and can take place in aqueous medium. In this way artificial
      formation of these compounds via condensation of biogenic amines with aldehydes
      or alpha-keto acids during the work-up procedure is eliminated. The procedure
      results in hydrophobic compounds, which are quantitatively extractable by liquid
      liquid extraction with organic solvents. Further clean-up was performed by solid
      phase extraction on C18 sample preparation columns.

PMID- 8263096
TI  - Confirmatory analysis of clenbuterol using two different derivatives
      simultaneously.
AB  - To meet the requirements of the European Community for confirmatory analysis of
      clenbuterol using low-resolution mass spectrometry, usually two different
      techniques (i.e. electron impact and chemical ionization) have to be applied to
      confirm unambiguously its presence in extracts of urine. This paper describes the
      application of two different derivatives and the simultaneous analysis of these
      two different derivatives in one gas chromatographic-mass spectrometric analysis.
      With the proposed combination of techniques, Community requirements can more
      easily be met in only one analytical run. Examples of the analysis of some urine
      samples are presented, as well as data on linearity, repeatability and
      equivalence of the combined technique to separate determinations.

PMID- 8263097
TI  - Simultaneous determination of ethylene glycol, propylene glycol, 1,3-butylene
      glycol and 2,3-butylene glycol in human serum and urine by wide-bore column gas
      chromatography.
AB  - A method has been developed for the separation and measurement of ethylene glycol
      and three other glycols (propylene glycol, 1,3-butylene glycol and 2,3-butylene
      glycol) in biological samples by wide-bore column gas chromatography with a flame
      ionization detector. The method used 1,3-propylene glycol (1,3-propanediol) as an
      internal standard. The method was linear at least from 2 to 1000 micrograms/ml,
      with a detection limit of 1 microgram/ml. Analytical recoveries were 89-98% for
      the different concentrations. Precision studies showed coefficients of variation
      of 1.5-7.7% for the different concentrations. The assay was applied to the
      analysis of biological samples from two patients who had ingested ethylene glycol
      and/or other glycols in a suicide attempt.

PMID- 8263098
TI  - Simultaneous determination of hydroquinone, catechol and phenol in urine using
      high-performance liquid chromatography with fluorimetric detection.
AB  - A method was developed for simultaneous determination of urinary hydroquinone,
      catechol and phenol using high-performance liquid chromatography (HPLC) with
      variable-wavelength fluorimetric detection. Urine samples, after acid hydrolysis,
      were saturated with sodium sulphate and extracted by diethyl ether. The two
      buffers used for gradient elution were (A) 10 mM sodium acetate containing 0.5%
      (v/v) acetic acid and (B) the same as buffer A but containing an additional 20%
      (v/v) acetonitrile. Hydroquinone, catechol and phenol were separated in a C18
      column and detected at 2.9, 6.8 and 13.6 min, respectively. The recovery and
      reproducibility were generally over 90%. Over 300 extracted samples were analysed
      and no change in column efficiency was noted. Comparisons were also made with
      HPLC using ultraviolet (UV) detection and with gas chromatography (GC). The
      proposed method appears to be more sensitive and reliable than other existing
      methods. This new method was also validated with urine samples collected from
      cigarette smokers and from refinery workers exposed to low concentrations of
      benzene.

PMID- 8263099
TI  - Sensitive determination of bisoprolol enantiomers in plasma and urine by high
      performance liquid chromatography using fluorescence detection, and application
      to preliminary study in humans.
AB  - A sensitive, stereoselective high-performance liquid chromatographic method with
      fluorescence detection for the measurement of bisoprolol enantiomers in human
      plasma and urine has been developed. Bisoprolol was extracted at alkaline pH with
      chloroform, followed by solid-phase extraction. The effluent was evaporated, and
      the reconstituted residue was chromatographed on a Chiralcel OD column with a
      mobile phase of hexane-2-propanol (10:0.9, v/v) containing 0.01% (v/v)
      diethylamine. Within the plasma and urine enantiomeric concentration ranges of 5
      100 ng/ml and 25-1250 ng/ml, respectively, a linear relationship was obtained
      between the peak-height ratios and the corresponding concentrations. The limit of
      quantitation, defined as three times the baseline noise, was 2 ng/ml for each
      enantiomer in plasma. A preliminary pharmacokinetic study was undertaken in three
      healthy male volunteers following an oral dose of 5 mg of racemic bisoprolol. The
      results confirm that this assay is suitable for pharmacokinetic studies of
      bisoprolol enantiomers in humans following oral administration of the therapeutic
      dose.

PMID- 8263100
TI  - Therapeutic monitoring of antituberculosis drugs by direct in-line extraction on
      a high-performance liquid chromatography system.
AB  - A direct in-line pre-column extraction technique in which guanidinium and
      ammonium sulfate are used, followed by column switching, was employed to analyze
      serum, plasma and cerebrospinal fluid samples of patients treated for tuberculous
      meningitis. Resolution of a wide range of polar to non-polar xenobiotics was
      obtained on a C8 silica column by using a linear gradient from a binary system
      consisting of solvent A (0.05 M KH2PO4) and solvent B (acetonitrile-isopropanol,
      4:1, v/v). Apart from the antituberculosis drugs (isoniazid, pyrazinamide,
      ethionamide and rifampicin) the patients received up to sixteen different
      medicines for prevention of complications and the treatment of symptoms.
      Qualitative resolution of all the drugs was obtained by the chromatographic
      system. Quantitation of pyrazinamide and ethionamide was achieved with high
      precision and low inter-sample variation.

PMID- 8263101
TI  - High-performance liquid chromatographic assay for human liver microsomal
      omeprazole metabolism.
AB  - Assays for the measurement of omeprazole metabolites in plasma and urine have
      been reported, but when applied to the determination of omeprazole metabolites
      formed by human liver microsomal incubations there were obvious limitations in
      sensitivity. The present high-performance liquid chromatographic (HPLC) assay,
      which comprises extraction, evaporation and reconstitution, is several-fold more
      sensitive with a limit of detection of approximately 2 pmol (2 nM in incubate)
      for omeprazole sulphone and 25 pmol (25 nM in incubate) for hydroxyomeprazole.
      Extraction efficiency is essentially quantitative and is highly reproducible
      (coefficient of variation = 2.1% for both metabolites). The assay is linear over
      a wide range of concentrations and the formation of the metabolites is linear
      with respect to both time (to 15 min) and protein concentration (to 1.5 mg/ml).
      Two minor metabolites, one of which was identified tentatively as 5-O
      desmethylomeprazole, were also formed by human liver microsomes and could be
      determined by this method. Preliminary studies of the formation of omeprazole
      sulphone and hydroxyomeprazole showed that the formation kinetics in human liver
      microsomes were biphasic for both metabolites, suggesting that at least two
      different cytochrome P450 isoforms are involved in their formation.

PMID- 8263102
TI  - Determination of L-methionine-dl-sulphoxide in tissue extracts.
AB  - The amino acid fraction from rat liver, heart and skeletal muscle was prepared by
      the separation of sulphosalicylic acid extract on Dowex 50 H+ form. The presence
      of L-methionine-dl-sulphoxide in these extracts was identified and compared by
      three independent chromatographic methods: ion-exchange, Pico-Tag and reversed
      phase high-performance liquid chromatography after precolumn derivatisation with
      diethylethoxymethylenemalonate. Quantitative data indicate that L-methionine-dl
      sulphoxide is present in the intracellular pool at the levels of free methionine.

PMID- 8263103
TI  - High-performance liquid chromatographic determination of histatins in human
      saliva.
AB  - A simple method for the assay of histatins in human saliva by high-performance
      liquid chromatography has been developed. The histatins in saliva were extracted
      with 0.1 M HCl-methanol, and histatins 1, 3, 5, and 6 were separated and
      concentrations were determined by reversed-phase chromatography. This simple
      method enabled the determination of levels of individual histatins from the
      saliva of normal subjects. The average concentration of histatins 1, 3, 5, and 6
      in parotid saliva collected from 26 healthy volunteers aged from 20 to 30 years
      were 11.25 +/- 5.65, 8.15 +/- 3.08, 7.67 +/- 3.12, and 1.56 +/- 0.53 mumol/l
      (mean +/- S.D.), respectively.

PMID- 8263104
TI  - Gas chromatographic determination of zopiclone in plasma after solid-phase
      extraction.
AB  - A gas chromatographic technique for determining zopiclone based on a solid-phase
      extraction procedure with C18 cartridge for sample clean-up is presented.
      Quantification can be achieved with 1 ml of plasma. The method uses prazepam as
      internal standard. Zopiclone is separated on a 5% phenyl methyl silicone
      analytical column and detected with an electron-capture detector, which
      consequently allows a limit of quantitation of 2 micrograms/l. It is thus simple,
      rapid, sensitive and linear over the range 5-2000 micrograms/l.

PMID- 8263105
TI  - Measurement of CI-979 (a candidate drug for the treatment of age-related
      disorders of cognition) in human plasma by capillary gas chromatography with
      nitrogen-selective detection.
AB  - A specific and highly sensitive method for the measurement of CI-979 in human
      plasma is described. The compound and internal standard were extracted from
      alkalinized plasma with methyl tert.-butyl ether and analyzed by capillary gas
      chromatography with nitrogen-selective detection. The method was demonstrated to
      be accurate and precise. Since the limit of quantitation was 0.10 ng/ml, this
      method was suitable for clinical pharmacokinetic studies in which subjects
      received repeated administration of 0.5-2.5 mg CI-979 every 6 h.

PMID- 8263106
TI  - Rapid determination of tetracycline antibiotics in serum by reversed-phase high
      performance liquid chromatography with fluorescence detection.
AB  - A rapid and accurate determination of tetracycline antibiotics in human serum by
      reversed-phase high-performance liquid chromatography with fluorescence detection
      has been developed, based on protein precipitation in serum. Various reagents for
      precipitation were investigated, and 24% trichloroacetic acid in methanolic
      solution gave the maximum recovery (at least 94.3%) and interference-free
      chromatograms of different three tetracyclines. At a concentration of 0.5
      micrograms/ml, the precision (relative standard deviation) ranged from 1.12 to
      1.94%. In the range 0.04-10.0 micrograms/ml for oxytetracycline and
      chlorotetracycline and 0.01-10.0 micrograms/ml for tetracycline, linear responses
      were observed. The detection limits of this method were 10-35 ng/ml for all three
      antibiotics. The proposed method was applied to the determination of serum
      concentrations in subjects receiving tetracycline antibiotics.

PMID- 8263107
TI  - Extractionless high-performance liquid chromatographic method for the
      determination of diclofenac in human plasma and urine.
AB  - An assay using reversed-phase high-performance liquid chromatography with
      ultraviolet detection, at 278 nm, was developed to measure diclofenac in human
      plasma and urine at concentrations suitable for biopharmaceutical studies.
      Indomethacin was used as internal standard and separation was performed at 40
      degrees C on a C18 Spherisorb column with acetonitrile-0.1 M sodium acetate
      (35:65, v/v) (pH 6.3) as mobile phase. The sample preparation is simple and rapid
      (extractionless), and the total run time is less than 5 min. The retention time
      is 2.8 min for diclofenac and 3.6 min for indomethacin. The detection limit is
      0.2 microgram/ml using a 20-microliters loop.

PMID- 8263108
TI  - Stereospecific high-performance liquid chromatographic assay of ibuprofen:
      improved sensitivity and sample processing efficiency.
AB  - A high-performance liquid chromatographic (HPLC) assay suitable for the analysis
      of the enantiomers of the non-steroidal anti-inflammatory drug ibuprofen (IB) in
      plasma was developed. Following the addition of racemic fenoprofen as internal
      standard (I.S.), samples are acidified and extracted with a mixture of isooctane
      isopropanol (95:5, v/v). After evaporation of the organic layer, the drug and
      I.S. are derivatized with S-(-)-1(1-naphthyl)ethylamine (S-NEA) after addition of
      ethyl chloroformate as the coupling reagent. Ethanolamine is added 3 min after
      the addition of S-NEA to react with the excessive ethyl chloroformate. The
      resultant diastereomers corresponding to IB and I.S. were chromatographed at
      ambient temperature on a 100 mm x 4.6 mm I.D. C18 reversed-phase column using
      acetonitrile-water-acetic acid-triethylamine (60:40:0.1:0.02) as the mobile phase
      pumped at a flow-rate of 1.2 ml/min. Detection of the fluorescent chromophore was
      at 280 and 320 nm for excitation and emission, respectively. The suitability of
      the assay for clinical pharmacokinetic studies of IB was determined by the
      analysis of plasma samples obtained from a healthy volunteer, following
      administration of a single 400-mg oral dose of racemic IB.

PMID- 8263109
TI  - High-performance liquid chromatographic method for stability and pharmacokinetic
      studies of nicorandil.
AB  - Nicorandil is a unique vasodilator that combines the actions of a potassium
      channel activator and a nitrovasodilator. Little literature is available on its
      chemical stability and pharmacokinetics in animals. We developed a simple,
      specific, sensitive, and precise high-performance liquid chromatographic method
      for the determination of nicorandil in aqueous solution and rat plasma, achieving
      a detection limit of 0.3 microgram/ml with 180-microliters samples. Nicorandil
      was found to be relatively stable between pH 2 and 10 at 37 degrees C (half-life
      = 461-84 h) and it is subjected to specific base catalysis above pH 10. Both
      chemical degradation and in vivo metabolism produced N-(2
      hydroxyethyl)nicotinamide, the denitrated product. Preliminary pharmacokinetic
      investigations showed that the assay is capable of quantitating nicorandil in rat
      plasma over a range of 0.3-100 micrograms/ml. These studies also suggested that
      the pharmacokinetics of nicorandil are dose-dependent.

PMID- 8263110
TI  - Determination of acyclovir by ultrafiltration and high-performance liquid
      chromatography.
AB  - A simple, sensitive and rapid high-performance liquid chromatographic (HPLC)
      procedure to determine total serum acyclovir concentrations is described. The
      assay involves a heat inactivation step at 56 degrees C to prevent risk of
      infection, ultrafiltration as a pretreatment step prior to ion-pair reversed
      phase liquid chromatography using guanosine as internal standard, and ultraviolet
      detection at 254 nm. This method has excellent recovery (97-100%), linearity (0.5
      100 mg/l) and precision (1.2-8.0% coefficient of variation). The detection limit
      is 50 micrograms/l. The assay proved to be suitable for therapeutic drug
      monitoring of acyclovir.

PMID- 8263111
TI  - Detection of Epstein-Barr virus transcripts in chemically or immunologically
      activated cells and in a null cell-line (HLN-STL-C) by in situ hybridization with
      alkaline phosphatase-linked oligonucleotide probes.
AB  - We report a simple procedure for the detection of Epstein-Barr virus (EBV) by in
      situ DNA-RNA hybridization with an alkaline phosphatase-linked oligonucleotide
      probe. EBV-producing cell lines P3HR-1 and Akata were treated with phorbol ester
      and n-butyrate, and anti-human IgG, respectively. This treatment resulted in
      highly increased populations of cells with EBV transcripts of the latent membrane
      protein 1 (LMP1) and envelop glycoprotein gp350/220, but not of EBV-encoded small
      nuclear RNAs (EBERs). Synthesis of the LMP1 protein, which was encoded by the
      induced mRNA, was mostly dependent on viral DNA synthesis, as shown by double or
      single labeling for in situ DNA-DNA hybridization with the oligo-nucleotide
      probe, and immunoperoxidase staining with a monoclonal antibody against LMP1. In
      situ hybridization of the null cell line HLN-STL-C established from an adult T
      cell leukemia patient showed that 100% of the cells contained both EBERs and LMP1
      mRNA and about 0.1% of the cells contained gp350/220 mRNA, indicating that a few
      of the null cells which carried the EBV genome spontaneously entered the late EBV
      replication cycle.

PMID- 8263112
TI  - Multiple primer pairs for polymerase chain reaction (PCR) amplification of human
      parvovirus B19 DNA.
AB  - Human parvovirus B19 is the etiologic agent of erythema infectiosum and transient
      aplastic crisis in patients with hemolytic anemias and has been associated with
      fetal death, arthritis, and chronic anemia. Acute B19 infection is best diagnosed
      by detection of IgM antibodies, whereas the diagnosis of chronic infection often
      requires the sensitivity of PCR to demonstrate presence of virus over time. To
      improve our ability to detect B19 DNA by polymerase chain reaction (PCR), we
      evaluated 19 primers combined into 16 different primer pairs for their ability to
      detect temporally and geographically diverse B19 isolates. All 16 pairs reacted
      with all isolates tested but with different sensitivity. Sequence analysis showed
      few nucleotide changes compared with published sequences. These changes did not
      explain observed differences in sensitivity between primer pairs. The most
      sensitive primer pairs detected 350 to 3500 DNA copies after 35 cycles. A second
      amplification cycle with nested primers improved the sensitivity 100-fold. These
      16 primer pairs provide the diagnostic virologist with multiple options for B19
      PCR assays.

PMID- 8263113
TI  - Flow cytometric analysis of the neutralizing immune response against infectious
      bursal disease virus using reticuloendotheliosis virus-transformed lymphoblastoid
      cell lines.
AB  - Infectious bursal disease virus (IBDV) is a lymphotropic virus with cytocidal
      effect on B lymphocytes of the bursa of Fabricius. We investigated the
      susceptibility of clonal populations of reticuloendotheliosis virus-transformed
      chicken B lymphocytes of both spleen and bursal origin to IBDV infection. The
      infected cells were metabolically-labelled and the viral polypeptides were
      analyzed by immunoprecipitation using monoclonal antibodies (MAbs). Virus
      adsorption and the effects of neutralizing convalescent antisera and MAbs on
      virus attachment were studied using flow cytometry. The results of the study
      indicate firstly that the transformed B cells support virus replication and
      provide an efficient system for studying IBDV-lymphocyte interactions. Secondly,
      results obtained also showed that the most potent neutralizing antibodies may not
      be those involved in preventing the receptor-mediated viral attachment but rather
      those involved in the inhibition of downstream events such as virus penetration
      or uncoating.

PMID- 8263114
TI  - Rapid identification of flaviviruses based on conserved NS5 gene sequences.
AB  - Two conserved regions in the sequence of the NS5 gene of Flaviviruses were
      identified. Primers were designed from the consensus sequence of these regions
      and were used in a reverse transcription/polymerase chain reaction (RT/PCR) to
      amplify a region of the central european tick-borne encephalitis virus Kumlinge
      NS5 gene. The authenticity of the amplified fragment was confirmed by nucleotide
      sequencing. A band of the expected size was also obtained when this RT/PCR was
      applied to 13 other flaviviral RNAs. This method may be useful for
      characterisation of the NS5 genes of flaviviruses and as a potential pan
      flavivirus diagnostic tool.

PMID- 8263115
TI  - Establishment and characterisation of murine cells constitutively expressing the
      fusion, nucleoprotein and matrix proteins of measles virus.
AB  - To advance our understanding of the immunobiology of measles virus (MV)
      infections, we have investigated the possibility of establishing cell lines
      constitutively expressing the individual MV antigens. In contrast to previously
      published studies, we show that it is possible to establish cell lines expressing
      high levels of fusion (F), nucleoprotein (NP) and matrix (M) MV proteins. Once
      cloned, the cell lines were stable with high levels of expression for more than
      six months. The size and cell distribution of the NP and F proteins were similar
      to those observed in MV- or vaccinia-MV recombinant-infected cells. In contrast,
      the distribution of the M protein, although being similar to that of MV-infected
      cells, differed from that of Vaccinia-M recombinant virus-infected cells.
      Preliminary results suggest that these cell lines will be useful tools for
      studying the contribution of individual MV antigens to the cell-mediated immune
      response to this virus.

PMID- 8263116
TI  - In vitro destabilization of plant viruses and cDNA synthesis.
AB  - DNA copies of a wide range of RNA viruses can be made by the direct addition of
      appropriately treated, purified virus particles to a reverse transcription
      reaction. Therefore, many problems associated with RNA isolation can be
      circumvented. Virus particles can be sufficiently destabilized by adjustments of
      salt content, buffer, pH or by the use of physical force supplied by a
      freeze/thaw cycle so that RNA in sufficient quantity and physical condition is
      available for the synthesis of in some cases, full length cDNAs. cDNAs have been
      made of viruses in the bromo-, poty-, carla-, ilar-, potex-, tobra and
      tobamovirus groups. Reported here are experiments with cowpea chlorotic mottle
      virus and bean common mosaic virus.

PMID- 8263117
TI  - Rapid and sensitive method for the detection of B19 virus DNA using the
      polymerase chain reaction with nested primers.
AB  - The sensitivity of detection of B19 virus DNA in clinical specimens was evaluated
      by comparing the results of single PCR and nested PCR assays, with or without
      subsequent Southern blot hybridization to a radiolabelled B19 DNA probe. The
      inhibitory activity of human serum components on polymerase reaction was also
      determined. The sensitivity of B19 virus DNA detection decreased by a factor of
      10(7) in the presence of 10% serum in the single PCR reaction mixture, and of
      10(3) for nested PCR. When nested PCR products were analysed by Southern blot
      hybridization to a B19 radioactive DNA probe, the sensitivity of the assay
      increased to such a level of B19 DNA detection that the reaction was no longer
      influenced by the presence of serum inhibitors in the original sample. Less than
      ten B19 genome copies could thus be detected in a 10-microliters sample. A panel
      of 38 clinical samples, originating from patients with possibility of B19 virus
      infection, were assayed by this method. Only one sample was found to be positive
      after single PCR, whereas seven samples (including the former) gave a positive
      signal after nested PCR. The specificity of the nested PCR products was
      controlled by hybridization to the B19 DNA probe and DNA sequencing. No
      discrepancy in the results was observed between nested PCR alone and nested PCR
      followed by Southern blot analysis.

PMID- 8263118
TI  - Serotype identification of Australian bluetongue viruses using a rapid
      fluorescence inhibition test.
AB  - Rapid serotyping of bluetongue virus (BTV) isolates is required to facilitate the
      choice of an appropriate serotype-specific vaccine in a disease situation or to
      improve surveillance of BTV serotype prevalence. This communication describes the
      development and validation of a bluetongue virus fluorescent inhibition test (BTV
      FIT) as a rapid method to serotype Australian BTV isolates. The BTV FIT uses
      virus neutralisation principles similar to those used in the rabies rapid
      fluorescent focus inhibition test. The BTV FIT has the ability to provide an
      accurate serotype identification within 24 h thereby abbreviating the serotyping
      process by 3-4 days relative to conventional virus neutralisation assays and
      making the BTV FIT comparable time-wise with the polymerase chain reaction
      technique. The development of the BTV FIT is described using BTV reference
      viruses which have been isolated in Australia, and validation of the assay by
      assessment of five Australian BTV isolates of unknown serotype by comparison with
      the plaque inhibition method. The use of the BTV FIT readily facilitated rapid
      and accurate serotype identification of Australian BTV reference viruses and five
      unknown BTV isolates with results indicating full agreement with the plaque
      inhibition method.

PMID- 8263119
TI  - Evaluation of the automated 'Enzymen-Test Anti HIV-1 + 2' and 'Enzymen-Test Anti
      HIV-1/2 selective' for the combined detection and differentiation of anti-HIV-1
      and anti-HIV-2 antibodies.
AB  - A new, modular automated ELISA (test 1) for HIV-1 and HIV-2 antibody detection
      and differentiation (Enzymun-Test Anti HIV-1 + 2; anti HIV 1/2 selective,
      Boehringer Mannheim) was compared with 3 alternative enzyme immunoassays (Abbott
      recombinant HIV-1/HIV-2 3rd generation EIA, Abbott (test 2); Enzygnost HIV 1 + 2,
      Behringwerke (test 3); and Wellcozyme HIV recombinant, Murex (test 4)) and
      Western blot (New LAV I Blot and New LAV II Blot; Diagnostics Pasteur). 380 serum
      samples from HIV-1 and HIV-2 seropositive patients at different stages of
      disease, high risk individuals, patients with conditions unrelated to AIDS and
      from healthy blood donors were used in this evaluation along with 6
      seroconversion panels, 6 serum dilution series and 'tricky' sera (repeatedly
      positive results in ELISA, but negative or undeterminate in Western blot; n =
      67). Using the Western blot as reference assay, the overall sensitivity of the
      four ELISAs was 100%. Test 4 showed the highest sensitivity for antibody
      detection in seroconversion and dilution series. A high specificity was achieved
      with test 1 (100%) and test 2 (99.4%). A relatively high rate of false positive
      results were obtained with test 2 (n = 12) and test 3 (n = 10) by testing
      'tricky' sera or samples obtained from healthy blood donors. In comparison to
      Western blot, a clear differentiation between HIV-1 and HIV-2 antibody serum
      samples was achieved with the Enzymun-Test. The results of the present study show
      that the Enzymun-Test provides reliable selective HIV-1 and HIV-2 antibody
      detection at a cost which is significantly lower than the costs of Western blot
      tests. Furthermore, the evaluation of test 1 suggests, that it is a highly
      specific assay for HIV antibody detection.

PMID- 8263120
TI  - Detection and typing of human herpesviruses by multiplex polymerase chain
      reaction.
AB  - A new approach to simultaneous detection and typing of related agents by the
      multiplex polymerase chain reaction (PCR) is described. The reaction was been
      applied to human herpesviruses by nested amplification of fragments of the DNA
      polymerase genes. During the first amplification, primers were used as two
      equimolar mixtures of non-degenerate oligonucleotides, aligning the 3'-ends with
      selected consensus regions, and their 5'-ends with the non-related sequences of
      each herpesvirus to be amplified. The specific fragments obtained were the
      substrate for a second, multiplex reaction for which primers were designed to
      produce different-size fragments for each related virus. The results showed high
      specificity for the detection and typing of the human herpesviruses with known
      sequences and no amplification of human DNA, in spite of the presence of the same
      consensus regions within human DNA polymerase alpha. It is concluded that this
      new approach would be useful for the differential diagnosis of herpesviruses, as
      well as for other groups of agents with conserved regions in their genomes and
      causing similar syndromes.

PMID- 8263121
TI  - Microtiter enzyme-linked immunosorbent assay using recombinant derived antigens
      versus western blot in the confirmation of presence of antibodies against the
      human immunodeficiency virus type 1.
AB  - A microtiter enzyme-linked immunosorbent assay using recombinant derived antigens
      was compared with the Western blot (Dupont) in the confirmation of the presence
      of antibodies against the human immunodeficiency virus type 1 (HIV-1). Of 104
      sera (104 individuals) that were negative by a screening ELISA, 91 were also
      negative by both confirmation assays. In three sera only the microtiter assay was
      found to be indeterminate, and in nine other sera only Western blot. The only
      microtiter assay positive serum was from a male patient at risk for infection
      with HIV. 279 sera from 83 patients were found positive by screening. Of these,
      223 sera were positive in both confirmation assays, and no serum was negative.
      Only one serum was indeterminate by the microtiter ELISA in contrast to 55 sera,
      including follow-up samples from 25 patients, most of whom had AIDS, by Western
      blot (Dupont criteria). However, the number of Western blot indeterminate sera
      decreased substantially applying less stringent criteria for interpretation. In
      conclusion, the microtiter ELISA performed well as a confirmation test for the
      presence of antibodies against HIV-1. In addition, the results demonstrate that
      in the microtiter assay the envelope peptide kp41 is highly discriminative in
      detecting anti-HIV-1 negative and anti-HIV-1 positive sera.

PMID- 8263122
TI  - HIV-1 pseudotype virus containing a Cocal virus genome and an HIV envelope:
      construction, assay and use.
AB  - A method is described for the production and assay of pseudotype viruses between
      human immunodeficiency virus type 1 (HIV-1) and Cocal virus (COV), containing an
      HIV-1 envelope and a COV genome (COV(HIV)). COV(HIV) pseudotype virus is a useful
      tool for the investigation of a variety of questions regarding HIV entry into
      susceptible cells, including steps in virus binding, fusion, and internalization,
      and the role of molecules which inhibit entry. COV, a rhabdovirus closely related
      to vesicular stomatitis virus (VSV), replicated and caused cytopathic effect in
      primary cultures of human peripheral blood lymphocytes (PBLs) and monocyte
      derived macrophages (MDM), and in human cell lines of lymphocytoid or monocytoid
      origin, making it an ideal candidate for pseudotype production. 174XCEM cells,
      which were permissive for selected macrophage-tropic strains as well as most
      lymphocyte-tropic strains of HIV-1, were used to produce stocks of putative
      pseudotype virus. To neutralize parental COV in these stocks, a rabbit antiserum
      was produced which had a neutralization index of > 10(7) at a dilution of 1:100.
      Using these methods, pseudotype viruses were produced with a titer of about 10(4)
      PFU per ml; these same stocks contained HIV-1 at a titer of about 10(5) TCD50 per
      ml and COV at a titer of about 10(8) PFU per ml. CD4-expressing HeLa cells were
      used to assay pseudotype stocks made with lymphocyte-tropic strains of HIV-1. The
      authenticity of the pseudotype stocks was validated by several controls,
      including their failure to register on congenic CD4-negative HeLa cells and their
      inhibition by monoclonal anti-CD4 antibodies such as Leu 3a.

PMID- 8263123
TI  - Detection of a shared idiotope on two encephalomyocarditis virus neutralizing
      monoclonal antibodies by neutralization inhibition enzyme immunoassay.
AB  - Idiotypic cross-reactivity between encephalomyocarditis virus (EMCV) neutralizing
      monoclonal antibodies UM 21.1 (IgG2b) and UM 21.3 (IgG2a) was detected by
      neutralization inhibition enzyme immunoassay using polyclonal and monoclonal anti
      idiotypic antibodies. One strongly cross-reactive anti-idiotypic monoclonal
      antibody, designated 21.1A5 (IgG2b), might recognize a recurrent idiotope on EMCV
      neutralizing antibodies but it did not induce EMCV neutralizing anti-anti
      idiotypic antibodies in homologous BALB/c mice.

PMID- 8263124
TI  - An in situ hybridization technique for the study of B19 human parvovirus
      replication in bone marrow cell cultures.
AB  - An in situ hybridization technique using digoxigenin labelling was developed to
      study B19 infection. By using appropriate DNA probes, transcription of structural
      and non-structural genes was detected in bone marrow cell cultures. Such a simple
      system is useful to the study of B19-cell interactions in non-permissive cell
      lines.

PMID- 8263125
TI  - Clinical review 51: Management of hypercalcemia.
AB  - Hypercalcemia is a very common electrolyte abnormality that is most often seen as
      a mild elevation in the setting of asymptomatic primary hyperparathyroidism. The
      hypercalcemia is usually less than 11.2 mg/dL and does not call for specific or
      vigorous approaches to management. However, more marked elevations in the serum
      calcium are also seen and call for a more specific approach to management. When
      the serum calcium is only moderately elevated, the therapeutic approach should be
      tempered by clinical assessments about the presence of symptoms and the
      underlying etiology. When the serum calcium is markedly elevated, a more targeted
      therapeutic approach is called for which now is independent of the presence of
      symptoms and usually of the underlying etiology. Considerations of hypercalcemia
      in these three different ranges will tailor the therapeutic approach to the
      clinical setting.

PMID- 8263126
TI  - Dinosaurs and steroids.

PMID- 8263127
TI  - The inositol-1,4,5-trisphosphate system is involved in rapid effects of
      aldosterone in human mononuclear leukocytes.
AB  - There is increasing evidence for rapid steroid action on electrolyte transport in
      human mononuclear leukocytes (HML). In HML, aldosterone stimulates the Na+/H+
      antiporter within a few minutes. Because a variety of hormones and growth factors
      activate the Na+/H+ antiporter via protein kinase C and inositol phospholipids, a
      possible involvement of inositol-1,4,5-trisphosphate (IP3) in the rapid effects
      of aldosterone in HML was investigated. The stimulation of IP3 generation was
      started by the addition of aldosterone, concanavalin A, or other steroids. A
      significant increase in IP3 levels by aldosterone (1 nmol/L, P < 0.05) was found
      after 1 min, similar to that found after concanavalin A (25 micrograms/mL).
      Aldosterone caused a concentration-dependent elevation of IP3 levels, with an
      apparent EC50 of approximately 0.1 nmol/L. Fludrocortisone stimulated IP3
      generation at similar concentrations, whereas a weaker IP3 stimulation by
      glucocorticoids (hydrocortisone, dexamethasone) occurred at micromolar
      concentrations only. Canrenone, a potent inhibitor of classical aldosterone
      action, was not effective up to a concentration of 100 nmol/L. These findings
      show kinetic and pharmacological similarities with both the functional data on
      Na+/H+ antiport stimulation by aldosterone and the studies of 125I-aldosterone
      binding to plasma membranes of HML. Thus, these data are the first to indicate an
      involvement of the phosphoinositide pathway in the rapid membrane effects of
      aldosterone.

PMID- 8263128
TI  - High affinity binding and direct antiproliferative effects of luteinizing hormone
      releasing hormone analogs in human endometrial cancer cell lines.
AB  - Although specific binding sites for LH-releasing hormone (LHRH) and its analogs
      have been demonstrated in biopsy samples of human endometrial cancer, their
      biological significance remains obscure. In this study we evaluated whether
      binding sites for LHRH are also present in the human endometrial cancer cell
      lines HEC-1A and Ishikawa and if such sites could mediate antiproliferative
      effects of LHRH analogs. Using [125I,D-Trp6]LHRH as a ligand, a high affinity/low
      capacity binding site was detected in both lines: HEC-1A line, dissociation
      constant (Kd)1 = 5.7 x 10(-9) mol/L, binding capacity (Bmax)1 = 78 fmol/10(6)
      cells; Ishikawa line, Kd1 = 4.2 x 10(-9) mol/L, Bmax1 = 29 fmol/10(6) cells. In
      addition, a second class of low affinity/high capacity binding sites for LHRH was
      demonstrated (HEC-1A line, Kd2 = 1.4 x 10(-6) mol/L, Bmax2 = 21 pmol/10(6) cells;
      Ishikawa, Kd2 = 4 x 10(-6) mol/L, Bmax2 = 32 pmol/10(6) cells). In the presence
      of 10(-5) mol/L agonist [D-Trp6]LHRH (triptorelin), the proliferation of HEC-1A
      and Ishikawa cell lines was significantly reduced to 76 +/- 2% and 88 +/- 4% of
      controls, respectively, after 24 h and to 64 +/- 2% and 62 +/- 2%, respectively,
      after 6 days. Dose-response experiments showed that lower concentrations (10(-9)
      mol/L) of the agonist decreased the proliferation to 80 +/- 1% for the HEC-1A
      line and 71 +/- 2% of controls for the Ishikawa line after 6 days.
      Antiproliferative effects are enhanced by increasing the doses of triptorelin and
      were maximal in this series of experiments at 10(-5) mol/L, the proliferation in
      the HEC-1A line being 62 +/- 1% and in the Ishikawa line 52 +/- 2% of controls,
      respectively. Similar time- and dose-dependent antiproliferative effects were
      obtained in both cell lines with the LHRH antagonist SB-75 (cetrorelix). These
      data suggest that LHRH analogs can directly inhibit the proliferation of human
      endometrial cancer cells in vitro. This direct action could be mediated through
      the high affinity LHRH binding sites.

PMID- 8263129
TI  - Androgens regulate proliferation of human prostate cancer cells in culture by
      increasing transforming growth factor-alpha (TGF-alpha) and epidermal growth
      factor (EGF)/TGF-alpha receptor.
AB  - Androgens affect growth of the prostate gland and many prostate cancers.
      Androgens could mediate their mitogenic effects on prostate cells by an autocrine
      loop involving epidermal growth factor (EGF) and transforming growth factor (TGF)
      alpha that bind to the EGF/TGF-alpha receptor. We examined the effects of 5 alpha
      dihydrotestosterone (DHT) and testosterone (T), EGF, and EGF-alpha on cell
      proliferation and 3H-thymidine incorporation in an androgen-dependent human
      prostate cancer cell line, ALVA101, in serum-free medium. The regulation of TGF
      alpha and EGF/TGF-alpha receptor messenger RNA (mRNA) levels were determined by
      Northern blot analysis and EGF/TGF-alpha receptor protein by immunoblot. After 24
      h of treatment of ALVA101 cells with DHT (10(-8) M) or T (10(-8) M), TGF-alpha
      mRNA levels increased 3- and 2.5-fold, respectively, and EGF/TGF-alpha receptor
      mRNA levels 2- and 1.5-fold, respectively. Cell numbers increased at day 5 in
      response to 10(-8) M DHT (18%, P < 0.01), 10(-8) M T (15%, P < 0.01), 20 ng/ml
      EGF (16%, P < 0.01), and 50 ng/mL TGF-alpha (34%, P < 0.01). DHT combined with
      TGF-alpha or T combined with EGF increased cell number 43% and 40% above control,
      respectively (P < 0.01 vs. DHT, P < 0.05 vs. TGF-alpha, T, EGF alone). The anti
      EGF/TGF-alpha receptor antibody (528) blocked the cell proliferation induced by
      either DHT or TGF-alpha. We conclude that DHT and T stimulate synthesis of TGF
      alpha and EGF/TGF-alpha receptor mRNAs and EGF/TGF-alpha receptor content in
      ALVA101 cells. This mitogenic effect of androgen on ALVA101 cells may involve TGF
      alpha and the EGF/TGF-alpha receptor autocrine loop.

PMID- 8263130
TI  - Human fetal membranes inhibit spontaneous uterine contractions.
AB  - Fetal membranes are postulated to play a role in paracrine signaling during the
      initiation of labor in women. We developed a dual chamber-fetal membrane-uterine
      muscle model to study the effect of human fetal membranes on spontaneous uterine
      contractions. In this model, full-thickness fetal membranes (amnion, chorion, and
      maternal decidua) are sealed into a Plexiglass chamber. The membranes partition
      the chamber into a maternal and fetal compartment. Chorion and decidua face the
      maternal side, and amnion faces the fetal side. An estrogenized rat uterine
      muscle strip is anchored into the maternal side as a bioassay to measure effects
      of fetal membranes on uterine contractions. Fetal membranes cause a 40% decrease
      in uterine contractions compared to basal condition (no membranes). Inhibition is
      reversible after removal of the membranes. The inhibition is specific to the
      chorion/decidual side because reversal of membranes with amnion toward the muscle
      did not show inhibition. Uterine contractions did not change over time in control
      chambers in which Parafilm substituted for membranes. A model for studying
      paracrine regulation of uterine contractions by human fetal membranes has been
      developed. The model provides evidence that fetal membranes inhibit uterine
      contractions. This inhibitory effect may contribute to uterine quiescence during
      pregnancy.

PMID- 8263131
TI  - Stress-induced activation of sympathetic nervous system is attenuated by the
      delta-opioid receptor agonist deltorphin in healthy man.
AB  - To examine the role of delta-opioid receptors in the regulation of the
      sympathoadrenomedullary system, the effects of the highly selective delta-opioid
      receptor agonist deltorphin (DT) on plasma catecholamine responses to insulin
      induced hypoglycemia (IIH) and cold pressor test (CPT) have been investigated in
      normal subjects in two separate studies. DT failed to modify basal plasma levels
      of both norepinephrine (NE) and epinephrine (E). DT completely suppressed the IIH
      evoked elevation of NE, whereas it attenuated the E response by 20%, with the DT
      induced decrease in E release failing to achieve statistical significance. DT
      completely blocked the release of both NE and E elicited by CPT. We conclude that
      specific delta-opioid receptor stimulation exerts an inhibitory effect on NE
      release induced by both IIH and CPT. These findings provide evidence that delta
      opioid receptors may influence the autonomic sympathetic reactivity.

PMID- 8263132
TI  - Overnight growth hormone secretion in short children: independence of the sleep
      pattern.
AB  - PURPOSE: to analyze the interrelationships between GH secretion and pattern of
      sleep. PATIENTS: 18 children (10 male, 8 female; mean age 9.1 yr, range 5.1-14.3
      yr), with short stature (mean height standard deviation score (SDS) -2.52, range 
      3.86-(-)1.88; mean height velocity SDS -1.1, range -2.40-(-)0.08), including 9
      children with genetic short stature and 9 with idiopathic short stature. METHODS:
      blood samples were taken every 15 min from 2000 h-0800 h, and GH profiles were
      analyzed by the PULSAR computerized peak identification algorithm; simultaneous
      sleep was analyzed by electroencephalogram recording. RESULTS: no significant
      correlation was noted between GH secretion parameters and any of the
      electroencephalogram parameters evaluated: stage 1 (S1) percent, stage 2 (S2)
      percent, slow-wave sleep (SWS) percent, rapid eye movement sleep percent,
      wakefulness (W) percent, and sleep efficiency (EFF); there was no significant
      difference in GH secretion between children with EFF less than 76% and those with
      EFF more than 76% (P > 0.5). Maximal GH peak coincided 9 times (50%) with SWS, 3
      times (17%) with S2, 3 times with W, twice (11%) with S1, and once (6%) with
      rapid eye movement sleep. First GH peak coincided 12 times (67%) with W, 3 times
      with S2, twice with SWS, and once with S1. There was no significant difference
      comparing the percentage of sleep stages occurring in the 15 min of maximal GH
      increment, in the 15 min preceding it, and in those following it; there was no
      significant difference comparing the percentage of sleep stages occurring in the
      15 min preceding the onset of a GH peak and in those following it. CONCLUSIONS:
      GH secretion in short children seems independent of the sleep stage and
      efficiency; in children it is possible that GH secretion relates with sleep per
      se and with neurohormonal changes occurring at nighttime rather than with a
      specific sleep stage or sleep stage sequence.

PMID- 8263133
TI  - Expression of insulin receptor spliced variants and their functional correlates
      in muscle from patients with non-insulin-dependent diabetes mellitus.
AB  - Due to alternative splicing of exon 11 of the receptor gene, the human insulin
      receptor exists in two forms, that have distinct tissue-specific expression and
      are functionally different. Needle biopsies obtained from vastus lateralis muscle
      from 20 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 20
      normal control subjects were analyzed for the relative expression of insulin
      receptor mRNA variants in a novel assay using fluorescence-labeled primers and
      subsequent analysis on an automated DNA sequencer. In subgroups of patients and
      control subjects, insulin binding and tyrosine kinase activity were examined in
      wheat germ agglutinin-purified insulin receptors isolated from muscle biopsies.
      Moreover, insulin-stimulated glucose disposal was studied by means of the
      euglycemic hyperinsulinemic clamp technique. No difference in the relative
      expression of spliced variants of the insulin receptor mRNA was observed (control
      subjects, 71.4 +/- 1.3% insulin receptor mRNA with exon 11; NIDDM patients, 71.5
      +/- 1.3% insulin receptor mRNA with exon 11). No significant interrelationships
      were demonstrated among the relative expression of insulin receptor mRNA
      variants, insulin binding, and tyrosine kinase activity toward the exogenous
      substrate poly(Glu-Tyr(4:1)). Furthermore, no significant relationship was
      demonstrated between the glucose disposal rate and the relative expression of
      insulin receptor splice variants. In conclusion, in skeletal muscle from both
      normal control subjects and NIDDM patients, the proportion of insulin receptor
      mRNA with exon 11 is about 70%. In addition, no significant correlations exist
      among insulin binding, insulin receptor tyrosine kinase activity, glucose
      disposal rate, and expression of alternative spliced insulin receptors in human
      skeletal muscle.

PMID- 8263134
TI  - High levels of human chorionic gonadotropin retard first trimester trophoblast
      invasion in vitro by decreasing urokinase plasminogen activator and collagenase
      activities.
AB  - Trophoblast cells of the blastocyst and of the first trimester placenta penetrate
      the endometrial basement membrane during the process of implantation and
      placental development. However, this invasive capacity seems to be restricted to
      the fetomaternal interface, as few trophoblast cells can be identified in the
      decidua, and trophoblasts rarely penetrate the maternal blood vessels. We have
      shown that the high invasive ability of first trimester human trophoblasts in
      vitro depends on collagenase activated by plasmin generation. In our study we
      used invasive first trimester trophoblast cells in conjunction with as in vitro
      amnion invasion assay to assess the role of hCG in the invasive process. hCG
      inhibited trophoblast invasion capacity in a dose-dependent fashion but exerted
      no effect on the ability of the trophoblasts to attach to the basement membrane.
      The activity of collagenase by trophoblasts (determined by zymography) was down
      regulated by hCG, again in a dose-dependent manner. In contrast, hCG had no
      effect on production of the tissue inhibitor of metalloproteinases. Similar
      inhibitory effects of hCG on urokinase-plasminogen activator (uPA) and the
      activity of trophoblast-conditioned media were shown (measured by degradation of
      S-2444). The hCG effect on collagenase production was not mediated by the
      expression of procollagenase messenger RNA (mRNA), the expression of the mRNA
      encoding tissue inhibitor of metalloproteinase, or the expression of uPA mRNA,
      suggesting posttranscriptional control of hCG action. High levels of hCG
      attenuated the activity of commercial uPA but had no effect on commercial
      collagenase activity. These observations suggest that hCG may play a role in the
      trophoblast invasion process by inhibition of uPA activity, in turn decreasing
      collagenase activity and thereby reducing trophoblast cell invasion.

PMID- 8263135
TI  - Racial differences in aldosterone excretion: a longitudinal study in children.
AB  - Aldosterone production, estimated from urinary excretion of aldosterone and the
      plasma aldosterone level, was found in a previous cross-sectional study to be
      lower in black children than white children. The present study examined
      aldosterone excretion longitudinally to determine whether the aldosterone
      excretion rate changed with time and if the racial difference in aldosterone
      excretion persisted. Urine samples were collected every 6 months for up to 5.5 yr
      in 351 white and 170 black children for measurements of aldosterone, sodium
      (Na+), and potassium (K+) excretion. Results were expressed per mumol urinary
      creatinine. Mean values for excretion rates for the total longitudinal period
      were determined. Na+ excretion was not significantly different in the two groups,
      whereas K+ excretion was 18% lower in blacks than whites (P = 0.0001). Body
      weight and urinary Na+ and K+ excretion were significantly related to aldosterone
      excretion. After adjusting for these variables, the aldosterone excretion rate
      was 35% lower in blacks than whites (P = 0.0001), a racial difference that did
      not change with age. Aldosterone excretion rates showed no longitudinal trend to
      either increase or decrease. The physiological relevance of the lower aldosterone
      excretion rate in black children remains unknown.

PMID- 8263136
TI  - Differential effects of aromatase inhibition on luteinizing hormone secretion in
      intact and castrated male cynomolgus macaques.
AB  - To understand the role of central aromatization in feedback regulation of LH in
      nonhuman primates, we treated adult male cynomolgus monkeys with the aromatase
      inhibitor, 1,4,6-androstatriene-3,17-dione (ATD). We measured LH, testosterone
      (T), and ATD in systemic sera of blood samples drawn on a diurnal schedule (0900
      and 2100 h). Each animal was bled for 4 pretreatment days from a femoral catheter
      after which they were divided into the following treatment groups: castrated
      (Cx), n = 2; Cx + T, n = 6; Cx + T + ATD, n = 6; Cx + ATD, n = 3; and sham
      operated + ATD, n = 3. Silastic capsules or packets containing T or ATD,
      respectively, were placed sc between the scapulae at the time of Cx or sham
      treatment. In T-treated animals, T (20 micrograms/kg body weight) dissolved in
      propylene glycol was injected im at 2100 h to mimic the diurnal rise of T
      observed in nonhuman primates. Animals were bled for 2 weeks after which they
      were killed, and selected brain areas were analyzed for aromatase activity and
      cytosolic and nuclear androgen receptors. Animals treated with ATD had
      significantly reduced levels of aromatase activity in selected regions of the
      hypothalamus, preoptic area, and the amygdala (P < 0.05). Even though ATD
      inhibited brain aromatase activity, it did not prevent the negative feedback
      actions of T on LH secretion after Cx. In addition, ATD by itself inhibited LH
      secretion after Cx and activated brain androgen receptors. These latter effects
      of ATD seemed to have been mediated through a metabolite. In sham-operated intact
      males, ATD produced variable surges of LH that were accompanied by elevations of
      T in the systemic circulation. These differential effects of ATD in intact vs.
      castrated animals demonstrate the importance of selecting the proper model system
      to study LH control mechanisms. In the intact animal, aromatization seems to play
      a role in regulating LH secretion, but the postcastration rise of LH seems to be
      regulated differently.

PMID- 8263137
TI  - Subcutaneous administration of the amino-terminal fragment of human parathyroid
      hormone-(1-34): kinetics and biochemical response in estrogenized osteoporotic
      patients.
AB  - A standard dose (400 U or 25 micrograms) of human (h) PTH-(1-34) was administered
      sc in 11 estrogen-treated patients with postmenopausal osteoporosis. Increments
      in circulating hPTH-(1-34) were brisk, peaking at 30 min, with variable peak
      levels averaging 10 times normal. Clearance of the peptide from the circulation
      followed an expontential pattern, with a mean t1/2 of 75 min. Peptide
      administration was followed by an immediate decline in serum concentrations of
      PTH-(1-84), which remained suppressed at about 65% of the basal value for the
      duration of the study (4 h). Serum calcium did not increase until 120 min, thus
      occurring after the diminution in PTH-(1-84). Serum phosphorus declined promptly
      as urinary phosphate excretion increased. There were no clear changes in urinary
      calcium excretion, but urinary cAMP excretion increased within 120 min. In 9 of
      11 patients, the serum concentration of 1,25-dihydroxyvitamin D increased, with
      mean levels increasing progressively after 90 min to approximately 30% above
      baseline (P < 0.05). In conclusion, sc administration of 25 micrograms hPTH-(1
      34) produces significant short term changes in mineral homeostasis that appear to
      be mediated by the kidney, parathyroid gland, and skeleton, with the latter
      displaying the most delayed response.

PMID- 8263138
TI  - Melatonin rhythms in women with anorexia nervosa and bulimia nervosa.
AB  - To discern whether the multiple neuroendocrine-metabolic dysfunctions observed in
      women with anorexia nervosa (AN) and bulimia nervosa (BN) are associated with
      altered diurnal variations in serum melatonin profiles, we compared cycling and
      amenorrheic women with normal weight BN (n = 8) and AN (n = 7) to 21 normal
      cycling controls. Endogenous depression, which has confounded prior studies of
      melatonin profiles in women with eating disorders, was excluded in all subjects.
      Serum samples for melatonin measurements were obtained at frequent intervals
      (every 20 min) in a controlled light-dark environment, and cycling women were
      studied in the early follicular phase of the menstrual cycle. Mean (+/- SE) peak
      melatonin levels were similar in AN, BN, and controls (325 +/- 43, 310 +/- 33,
      and 334 +/- 30 pmol/L, respectively). The time of melatonin peak, the time of
      onset and offset of the nocturnal serum melatonin excursion, and the duration of
      the nocturnal elevation were also similar in the three groups. Analysis of
      covariance revealed no independent effects of age or time of year on the data.
      Moreover, when subjects were separated into those with and without menstrual
      cyclicity, no significant differences in any parameter of melatonin diurnal
      variation were observed. Taken together, these data suggest that pineal melatonin
      secretion is unaltered in women with eating disorders, in whom depression is
      excluded, and that the frequent occurrence of amenorrhea in this population is
      not mediated by melatonin.

PMID- 8263139
TI  - Failure of combined follicle-stimulating hormone-testosterone administration to
      initiate and/or maintain spermatogenesis in men with hypogonadotropic
      hypogonadism.
AB  - In men with hypogonadotropic hypogonadism, prolonged treatment with LH and FSH
      induces spermatogenesis. To compare the respective role of exogenous testosterone
      and intratesticular testosterone on the induction and maintenance of
      spermatogenesis, 10 men with hypogonadotropic hypogonadism and without history of
      cryptorchidism were studied. They were treated with human gonadotropins (hMG; 150
      IU FSH and LH and 1500 IU hCG, im, three times weekly) or pure FSH (150 IU, im,
      three times a week) and testosterone (T: 250 mg, im, once a week). Five men were
      treated first with hMG-hCG and then with pure FSH plus T. The other five men
      started with pure FSH plus T. Each treatment period lasted 24 months. In all men,
      hMG-hCG induced spermatogenesis after 24 months, with normal motility and
      quality. The combination of pure FSH and T was not able to induce spermatogenesis
      after 24 months. In addition, sperm count dropped dramatically to 0.3 +/- 0.1 x
      10(6)/mL within 3 months and to 0 after 6 months when pure FSH and T followed
      [corrected] hMG-hCG. Plasma T levels were increased by both treatments, but
      significantly more after pure FSH and T (35.3 +/- 5.2 nmol/L) than after hMG-hCG
      (20.4 +/- 5.2 nmol/L; P < 0.05). Plasma estradiol levels after treatment with
      pure FSH and T were also increased, but the difference from those obtained during
      hMG-hCG treatment was not significant. In conclusion, in men with complete
      gonadotropin deficiency, FSH and exogenous T are not able to induce
      spermatogenesis. Furthermore, spermatogenesis induced by LH plus FSH (hMG-hCG)
      cannot be maintained when exogenous T replaced LH in the regimen. Thus, exogenous
      T is unable to replace LH (and intratesticular T) to induce spermatogenesis.
      These data are noteworthy in the prospect of male contraception after a complete
      blockade of gonadotropin activity.

PMID- 8263140
TI  - Association of HLA-DQB1*0201 with stiff-man syndrome.
AB  - Stiff-man syndrome (SMS) is a rare disorder of the central nervous system of
      probable autoimmune origin. Patients with SMS often have other autoimmune
      diseases, in particular type I (insulin-dependent) diabetes mellitus (IDDM).
      Approximately 60% of patients with SMS have high titers of autoantibodies against
      the enzyme glutamic acid decarboxylase. Similar to SMS, the majority of patients
      with IDDM have autoantibodies against glutamic acid decarboxylase at or before
      diabetes onset, although usually at a lower titer and with a different reaction
      pattern than patients with SMS. To investigate the immunogenetic basis of SMS, we
      HLA-typed 18 patients with the disease. Seventy-two percent carried the DQB1*0201
      allele (13 of 18, P = 0.02 vs. 18 of 48 controls), indicating that SMS is
      associated with this allele. DQB1*0201 is also a susceptibility allele for IDDM
      and other autoimmune diseases. Patients with SMS carried the IDDM-protective
      DQB1*0602 allele and other sequence-related DQB1*06 alleles with the same
      frequency observed in controls. In contrast, these alleles are rarely found in
      IDDM. Five of 8 (62.5%) SMS patients lacking a DQB1*06 allele were diabetic in
      contrast to only 2 of 10 (20%) with a DQB1*06 allele (P = 0.08), suggesting that
      the presence of DQB1*0602 or other DQB1*06 alleles may be associated with a
      reduced prevalence of diabetes among patients with SMS.

PMID- 8263141
TI  - Glucose transporter protein expression in human placenta throughout gestation and
      in intrauterine growth retardation.
AB  - Despite the importance of glucose for fetal growth, gestational development of
      placental glucose transport capacity has not been studied in the human.
      Furthermore, inadequate glucose transport has been implicated as a
      pathophysiological mechanism in intrauterine growth retardation (IUGR). We
      studied glucose transporter (GLUT) protein expression in sections of normal term
      placental tissue (immunocytochemistry) and in syncytiotrophoblast microvillous
      (MVM) and basal membranes (BM) isolated from normal term, preterm, and IUGR
      placentas (immunoblotting). GLUT 1, but not GLUT 3, protein was abundantly
      present in syncytiotrophoblast membranes. MVM had approximately 3-fold higher
      GLUT 1 density than BM at term. MVM GLUT 1 density was maintained from 16 weeks
      of gestation to term. BM GLUT 1 density increased 2-fold in late second trimester
      and remained unaltered thereafter to term. GLUT 1 densities in term and preterm
      IUGR placentas were unaltered. Net D-glucose uptake rates corresponded to the
      GLUT 1 densities. These data suggest that 1) GLUT 1 is the main glucose
      transporter protein isoform in human syncytiotrophoblast; 2) the glucose
      transport capacity for MVM is potentially approximately 20-fold higher than that
      of BM; 3) GLUT 1 densities may be regulated independently in MVM and BM; 4) the
      increase in surface area and the maintenance of a high GLUT 1 density can account
      for the increase in placental glucose transport in the latter part of pregnancy;
      and 5) fetal hypoglycemia in IUGR is not due to a decrease in placental glucose
      transporter density.

PMID- 8263142
TI  - Short-term effects of recombinant human insulin-like growth factor I on metabolic
      control of patients with type II diabetes mellitus.
AB  - Recombinant human insulin-like growth factor I (rhIGF-I) lowers blood glucose,
      serum insulin, C-peptide, and lipid levels in healthy and diabetic animals and
      humans. We hypothesized that rhIGF-I might control blood glucose levels and
      concomitantly reduce pancreatic insulin secretion in patients with type II
      diabetes. If true, rhIGF-I might serve as a therapeutic agent that could mitigate
      some of the detrimental effects of hyperinsulinemia secondary to insulin
      resistance in these patients. In this study, we treated 12 patients with type II
      diabetes mellitus twice daily for 5 days with sc rhIGF-I in doses of 90, 120, or
      160 micrograms/kg body weight. Metabolic parameters in the fasting and
      postprandial states were assessed during a 3-day baseline period, the rhIGF-I
      treatment period, and a 3-day follow-up period, respectively. Administration of
      rhIGF-I significantly reduced mean (+/- SD) concentrations of fasting blood
      glucose (12.3 +/- 4.5 to 9.1 +/- 2.6 mmol/L), serum insulin (98 +/- 52 to 56 +/-
      27 pmol/L), and C-peptide (993 +/- 298 to 728 +/- 232 pmol/L). It also decreased
      postprandial (area under the curve) blood glucose (32.5 +/- 12.7 to 23.9 +/- 8.1
      mmol/L.h), serum insulin (1102 +/- 707 to 467 +/- 332 pmol/L.h), and C-peptide
      (5958 +/- 2747 to 3442 +/- 1523 pmol/L.h). The administration of rhIGF-I was also
      associated with a small but significant reduction in serum triglycerides (6.76 +/
      3.45 to 5.32 +/- 2.59 mmol/L) and total cholesterol (6.13 +/- 1.25 to 5.66 +/-
      1.20 mmol/L), 24-h creatinine clearance increased significantly (85 +/- 30 to 133
      +/- 51 mL/min), and microalbuminuria was unchanged. Although rhIGF-I was
      reasonably well tolerated, side effects included low-grade edema, mild and mainly
      asymptomatic orthostatic hypotension, and bilateral temporomandibular tenderness.
      We conclude that short-term treatment of type II diabetic patients with rhIGF-I
      favorably affects metabolic control and enhances kidney function. An assessment
      of the risk/benefit ratio of rhIGF-I administration to this group of patients
      awaits extended experiments.

PMID- 8263143
TI  - Familial unresponsiveness to thyrotropin by autosomal recessive inheritance.
AB  - Unresponsiveness to TSH has been identified and sufficiently studied in only
      three patients. We report siblings with this defect as the first documentation of
      familial occurrence. A 26-yr-old woman was diagnosed with congenital
      hypothyroidism during infancy. The thyroid was atrophic, and thyroid function
      tests without T4 replacement showed serum free T4 levels below 3 pmol/L, serum
      TSH of 125 mU/L, and serum thyroglobulin below 5 mg/L. 123I scintigram showed
      decreased uptake (5% at 24 h), but normal shape at the correct position in the
      neck. Autoantibodies against thyroglobulin, thyroid peroxidase, and TSH receptor
      in serum were not detected. The amount of cAMP released into FRTL-5 cell culture
      in the presence of TSH from the patient was not different from that released by
      the same amount of TSH from normal subjects, suggesting that TSH bioactivity in
      our patient was normal. The brother of the patient also had congenital
      hypothyroidism, and the data on his thyroid function was similar to that for his
      sister. There was a consanguineous marriage in the parents of the siblings, and
      the mother of the patients had a normal serum free T4 level, but slightly
      increased serum TSH and thyroglobulin levels, indicating subclinical
      hypothyroidism. The possible pathogenesis of TSH unresponsiveness in our patients
      includes a mutation in the TSH receptor gene, abnormality in transcription
      regulating factor, abnormality in GTP-binding protein, and/or inhibition of the
      action of cAMP. The family history of the patients suggests that the mode of
      inheritance in TSH unresponsiveness is autosomal recessive.

PMID- 8263144
TI  - Effects of nicotinamide supplementation on human pancreatic islet function in
      tissue culture.
AB  - Nicotinamide currently attracts considerable interest as a compound that might
      prevent the development of human insulin-dependent diabetes mellitus. The present
      study investigated the direct actions of nicotinamide on human pancreatic beta
      cells. For this purpose, islets were isolated from 11 adult cadaveric donors. The
      human islets were subsequently precultured in RPMI-1640 (5.6 mmol/L glucose) and
      10% fetal calf serum for 3-4 days. The islets were cultured for another 6 days in
      the same medium in either the presence or absence of 10 mmol/L nicotinamide, and
      subsequently, islet function was examined. After culture, both groups of islets
      contained similar amounts of DNA, and DNA synthesis, determined by the tritiated
      thymidine incorporation rate, was unchanged. The insulin content both on a per
      islet basis and per DNA was similar in both groups as was the islet glucose
      oxidation rate. Insulin accumulation into the culture medium was sustained over
      the entire culture period and did not differ at any time point between the
      nicotinamide and the control group. Nicotinamide affected neither basal and
      glucose-stimulated insulin secretion nor (pro)insulin and total protein
      biosynthesis rates after culture. The insulin response to glucose of the human
      islets was about 5-fold. In conclusion, the present study shows that nicotinamide
      does not directly affect human beta-cell function or the cell replicatory rate.
      This would suggest that any potential beneficial effects observed after treatment
      with nicotinamide in patients with insulin-dependent diabetes mellitus may not
      necessarily reflect an action at the beta-cell level.

PMID- 8263145
TI  - Hyponatremia and osmoregulation of thirst and vasopressin secretion in patients
      with adrenal insufficiency.
AB  - To clarify the mechanism underlying abnormal vasopressin (AVP) secretion in
      glucocorticoid deficiency, we examined the response of AVP secretion to osmotic
      stimulus produced by 5% saline infusion and analyzed the possible causative
      factors in seven patients with hypoosmolal hyponatremia resulting from adrenal
      insufficiency. In all patients, urinary sodium excretion persisted with urine
      osmolality exceeding plasma osmolality, and plasma AVP levels relative to plasma
      osmolality were elevated. Blood urea nitrogen, plasma creatinine, and PRA ranged
      from low to normal. All patients had nausea or vomiting, three had hypotension,
      and two had hypoglycemia; however, the primary cause of increased AVP secretion
      was attributed to none of these stimuli. After 5% saline infusion, patterns of
      changes in plasma AVP levels in individual patients were variable: levels
      decreased with increasing plasma osmolality in two patients and remained
      unchanged in the other five patients. Despite hyponatremia and absence of
      hypovolemia, thirst was present in the five patients, who responded normally to
      questions. This abnormality in AVP secretion and thirst was corrected after
      glucocorticoid replacement with normalization of plasma sodium concentrations and
      osmolality. Thus, glucocorticoid deficiency in man results in a clinical picture
      almost indistinguishable from that of the syndrome of inappropriate secretion of
      antidiuretic hormone. Persistent AVP secretion in this pathological state is due
      to a loss of hypotonic suppression of the osmostat for AVP release, which may be
      occasioned primarily by glucocorticoid deficiency per se and aggravated
      secondarily by multiple nonosmotic stimuli including nausea, hypotension, and
      hypoglycemia.

PMID- 8263146
TI  - Marked effects of sustained low growth hormone (GH) levels on day-to-day fuel
      metabolism: studies in GH-deficient patients and healthy untreated subjects.
AB  - The metabolic effects of circadian GH levels in the very low physiological range
      are unknown. Therefore, we studied 1) GH-deficient patients on receiving GH
      replacement therapy in whom the last GH injection was replaced with a constant iv
      infusion starting at 24 h of either GH (35 micrograms/h) or saline (SAL), and 2)
      an untreated healthy control group. Glucose turnover, indirect calorimetry, and
      forearm exchange of metabolites were investigated the following day in the basal
      state (8-11 h) and during a euglycemic (11-13 H) and a hypoglycemic (13-14 h)
      glucose clamp. During infusion, steady state GH levels increased by 1.9
      micrograms/L. Basal and insulin-stimulated energy expenditures (EE) were lower in
      the patients during SAL than during GH infusion, and the basal respiratory
      exchange ratio was also lower during GH treatment. Protein EE was elevated during
      SAL compared to GH infusion (P < 0.05). During the clamp, forearm glucose uptake
      decreased in the GH study compared to that in the SAL study ((P < 0.05). The
      patients in the SAL study were more sensitive to insulin during the clamp in
      terms of suppression of endogenous glucose production (EGP; P < 0.05) and
      infusion rate of glucose necessary to maintain euglycemia (M value; P < 0.01).
      Lipid oxidation, in particular in the basal state, was decreased during SAL
      compared to GH infusion (P < 0.01). The SAL-treated compared with the control
      group was characterized by decreased basal and insulin-stimulated EE (P < 0.01),
      increased protein EE (P < 0.01), and hypersensitivity to insulin in terms of
      suppression of EGP (P < 0.05) and M value (P < 0.01). During the hypoglycemic
      clamp, the patients in the SAL study were hypersensitive to the hypoglycemic
      actions of insulin in terms of increased M-value and suppression of EGP, and
      lipolysis was impaired, as judged by the inhibition of net forearm uptake of FFA.
      In conclusion, very low GH levels exert powerful actions on day-to-day
      metabolism, resulting in protein and glucose sparing at the expense of lipids.

PMID- 8263147
TI  - The impact of subchronic hypercortisolemia on progesterone metabolism and the
      luteinizing hormone-progesterone axis in the cynomolgus monkey.
AB  - The purpose of the study was to assess the impact of subchronic hypercortisolemia
      on progesterone (P) metabolism and production and on peripheral LH levels in a
      nonhuman primate using a repeated measures experimental design. Osmotic pumps
      that released hydrocortisone phosphate (HP) at a dose of 15 mg/day were implanted
      sc in seven cynomolgus monkeys for two menstrual cycles. The pumps were filled
      with saline for the two control cycles, which either preceded (three animals) or
      followed (four animals) HP infusion. P metabolism, P production, and episodic
      secretion of LH were determined 8 +/- 1 days after the serum estradiol peak in
      the second control cycle and in the second cycle of HP infusion in each monkey,
      after iv bolus administration of 50 microCi [3H]P, followed by a 6-h blood
      sampling period. HP infusion elevated serum cortisol levels 1.6-fold. Serum P
      levels were decreased throughout the luteal phase by 58% (P < 0.01). The MCR of P
      and the volume of distribution at steady state of P were increased by 200% during
      HP infusion (both P < 0.005). The production rate of P was increased by HP
      treatment in five of seven monkeys. HP infusion increased the ratio of 20 alpha
      [3H]dihydroprogesterone to [3H]P in serum from 0.5 to 1.0 (P < 0.05) while
      decreasing the fraction of [3H]P and its metabolites excreted in urine from 20%
      to 11% (P < 0.05). Serum LH levels, determined over a 5.25-h period in the luteal
      phase, were elevated by 200% during HP treatment (P < 0.05). Episodic secretion
      of LH during treatment was characterized by a 660% increase in the pulse
      amplitude (P < 0.05) and an apparent decrease in the pulse frequency. The results
      of this study provide evidence that moderate elevation of serum cortisol levels
      for two menstrual cycles in primates 1) increases the MCR of P, which may be the
      cause of the observed decrease in serum P levels; and 2) elevates serum LH levels
      by amplifying its pulse amplitude, which may result in a compensatory rise in the
      production rate of P.

PMID- 8263148
TI  - Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol
      levels in amenorrheic athletes: effects of endogenous hormone status and nutrient
      intake.
AB  - To determine the interactive effects of hormones, exercise, and diet on plasma
      lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake,
      and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in
      24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared
      to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma
      cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride
      (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein
      (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density
      lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2
      (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL
      cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and
      apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic
      athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3
      g/day, P = 0.02), but similar amounts of calories, cholesterol, protein,
      carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects
      correlated positively with the percent of dietary calories from fat (r = 0.42, n
      = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23,
      P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular
      risk by increasing plasma LDL and total cholesterol. However, cardioprotective
      elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of
      cardiovascular disease in amenorrheic athletes.

PMID- 8263149
TI  - Relationship of sex hormones to lipids and lipoproteins in nondiabetic men.
AB  - Although many studies show that increased androgenicity is associated with
      increased triglyceride (TG) and decreased high density lipoprotein cholesterol in
      both pre- and postmenopausal women, relatively few data are available on the
      association of sex hormones to lipids and lipoproteins in men. We examined the
      association of sex hormone-binding globulin (SHBG), total and free testosterone,
      dehydroepiandrosterone sulfate (DHEA-SO4), and estradiol with lipids and
      lipoproteins in 178 nondiabetic men from the San Antonio Heart Study, a
      population-based study of diabetes and cardiovascular disease. The TG
      concentration was significantly inversely related to SHBG (r = -0.22), free
      testosterone (r = -0.15), total testosterone (r = -0.22), and DHEA-SO4 (r = 
      0.16). High density lipoprotein (HDL) cholesterol was significantly positively
      correlated to SHBG (r = 0.21), free testosterone (r = 0.15), total testosterone
      (r = 0.17), and DHEA-SO4 (r = 0.16). Total testosterone was significantly related
      to total cholesterol (r = -0.17) and low density lipoprotein cholesterol (r = 
      0.15). After adjustment for age, body mass index, waist to hip ratio, and glucose
      and insulin concentrations, TG concentrations remained significantly related to
      SHBG (r = -0.20), free testosterone (r = -0.15), and DHEA-SO4 (r = -0.18), and
      HDL cholesterol remained significantly associated with SHBG (r = 0.17), free
      testosterone (r = 0.15), total testosterone (r = 0.14), and DHEA-SO4 (r = 0.16).
      In conclusion, we observed a less atherogenic lipid and lipoprotein profile with
      increased testosterone concentrations. This was not explained by differences in
      glucose or insulin concentrations. However, sex hormones explained only a small
      percentage of the variation in total TG and HDL cholesterol concentrations. These
      findings are in striking contrast to data from women, in whom increased
      androgenicity is strongly associated with increased TG and decreased HDL
      cholesterol levels.

PMID- 8263150
TI  - Use of tissue-specific promoters in the regulation of aromatase cytochrome P450
      gene expression in human testicular and ovarian sex cord tumors, as well as in
      normal fetal and adult gonads.
AB  - We have previously demonstrated that the tissue-specific regulation of human
      aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence
      of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific
      transcripts are expressed in the placenta, whereas promoter II (PII) appears to
      be the only active promoter in the corpus luteum. Testicular and ovarian sex cord
      tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal
      boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have
      been previously reported. In the present study, we investigated the regulatory
      elements directing P450arom gene transcription in samples of SCTAT from three
      prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an
      adult woman, as well as in healthy fetal and adult testicular and ovarian
      tissues. Placental tissue was used as a control. Using polymerase chain reaction
      linked to reverse transcription and northern blotting, we determined the tissue
      specific use of various P450arom promoters by analyzing specific 5'-termini from
      messenger RNA templates. Results indicate a universal gonadal promoter (PII)
      directs P450arom gene expression in healthy fetal and adult ovaries and testes,
      as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These
      results are interpreted to mean that use of PII in human ovary and testis is
      preserved from the fetal period into adult life as well as in transformed
      neoplastic Sertoli and granulosa cells. On the other hand, transcripts from
      placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT,
      immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells,
      whereas the normal-appearing sex cords do not contain any immunoreactive
      P450arom. These results further suggest that the markedly increased aromatase
      expression of these transformed neoplastic cells is not a consequence of using
      different tissue-specific promoters. Rather it appears to involve activation (or
      failure of inhibition) of the upstream regulatory elements of the same promoter,
      which is normally functional in all gonadal tissues, namely the proximal PII.

PMID- 8263151
TI  - Twenty-four-hour concentration profiles of gonadotropin and estradiol (E2) in
      prepubertal and early pubertal girls: the diurnal rise of E2 is opposite the
      nocturnal rise of gonadotropin.
AB  - To investigate the detailed pattern of circulating gonadotropin and estradiol
      (E2) concentrations around the onset of puberty, plasma gonadotropin and E2 were
      measured at 20-min intervals for 24 h in seven prepubertal and six early pubertal
      normal short girls. The hormone concentrations obtained were analyzed by Cluster
      pulse detection algorithm, cosinor analysis, and cross-correlation analysis. All
      subjects showed spontaneous LH and FSH pulses, and six early pubertal girls
      showed spontaneous E2 pulses. Cosinor analysis revealed 24-h LH rhythms in all
      subjects except two early pubertal girls and 24-h FSH rhythms in all subjects
      except one early pubertal girl. The acrophases (clocktime for maximal value) in
      the 24-h rhythm of LH and FSH were both found in the late hours of sleep. All
      subjects except three prepubertal girls showed significant 24-h E2 rhythms. In
      contrast to the 24-h LH and FSH rhythms, the acrophase of the 24-h E2 rhythm was
      found in the daytime waking period. Cross-correlation analysis demonstrated
      significant positive cross-correlations between LH and E2 that were maximum at an
      E2 lag of 5.7-9.3 h in three of the six early pubertal girls. In conclusion, the
      E2 concentration profiles in girls around the onset of puberty show marked 24-h
      rhythm, with acrophase during the daytime waking period. There exists a 5.7- to
      9.3-h time lag between LH and E2 time series, and this long time lag might
      correspond to the time required for aromatization for E2 synthesis.

PMID- 8263152
TI  - Normal basal and insulin-stimulated fuel metabolism in lean women with the
      polycystic ovary syndrome.
AB  - Many reports have suggested that hyperandrogenaemic patients with the polycystic
      ovary syndrome (PCOS) may be insulin resistant. However, there have also been
      suggestions that their insulin resistance may relate to obesity and android fat
      distribution. To assess whether PCOS induces metabolic disturbances independently
      of obesity, we studied seven lean patients with PCOS (age, 27.1 +/- 2.0 yr; body
      mass index, 22.2 +/- 0.78 kg/m2; waist/hip ratio, 0.79 +/- 0.02; fat-free mass,
      46.38 +/- 1.13 kg) and seven normal women (age, 25.7 +/- 1.4 yr; body mass index,
      21.3 +/- 0.69 kg/m2; waist/hip ratio, 0.74 +/- 0.02; fat-free mass, 50.1 +/- 1.51
      kg) for 3 h in the basal period and 2 h during a hyperinsulinemic (0.4 mU/kg.min)
      euglycemic clamp. In the basal state, comparable metabolic indices were recorded:
      serum insulin, 35.9 +/- 7.7 (PCOS) vs. 37.3 +/- 2.87 pmol/L (controls); plasma C
      peptide, 364.1 +/- 66.2 vs. 397.2 +/- 66.2 pmol/L; plasma glucose, 4.95 +/- 0.09
      vs. 4.77 +/- 0.09 mmol/L; forearm arterio-venous difference in glucose, 0.17 +/-
      0.04 vs. 0.15 +/- 0.07 mmol/L; isotopically determined endogenous glucose
      production, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 mg/kg.min; and serum nonesterified fatty
      acids, 545 +/- 40 vs. 617 +/- 54 mumol/L (all P > 0.05). During the clamp, all
      recordings were again similar: serum insulin, 282.7 +/- 21.5 vs. 270.5 +/- 13.6
      pmol/L; plasma C-peptide, 331.0 +/- 33.1 vs. 364.1 +/- 66.2 pmol/L; plasma
      glucose, 4.99 +/- 0.07 vs. 4.99 +/- 0.05 mmol/L; glucose arterio-venous
      difference, 1.01 +/- 0.18 vs. 0.85 +/- 0.12 mmol/L; endogenous glucose
      production, -0.9 +/- 0.1 vs. -0.5 +/- 0.2 mg/kg.min; amount of exogenous glucose
      necessary to maintain euglycemia, 4.0 +/- 0.4 vs. 3.8 +/- 0.5 mg/kg.min; and
      nonesterified fatty acids, 205 +/- 7 vs. 246 +/- 18 mumol/L (all P > 0.05). By
      showing normal basal and insulin-stimulated substrate metabolism in lean
      hyperandrogenemic PCOS patients, these data suggest that insulin resistance may
      be an epiphenomenon, rather than a primary feature of PCOS.

PMID- 8263153
TI  - Peripheral monocyte culture supernatants of menopausal women can induce bone
      resorption: involvement of cytokines.
AB  - Increased bone resorption is a mechanism contributing to bone loss in the
      postmenopausal period. Cytokines are involved in osteoclastic differentiation
      and, therefore, may play a role in the regulation of bone resorption. Several
      previous works showed the implication of interleukin-1 (IL-1), IL-6, and tumor
      necrosis factor-alpha (TNF alpha) in the modulation of bone remodeling. This
      study determines the concomitant production of the three cytokines and tests the
      bone-resorbing activity of peripheral monocyte supernatants. Four groups of women
      were studied: premenopausal women (n = 13; mean age, 47 +/- 0.9 yr), untreated
      postmenopausal women (n = 21; mean age, 52 +/- 0.6 yr), postmenopausal women
      treated with estrogens (n = 14; mean age, 54.2 +/- 1.1 yr), or postmenopausal
      women treated with ethanehydroxydiphosphonate (n = 12; mean age, 53.2 +/- 2 yr).
      Assignment to clinical groups was verified by plasma FSH and estradiol
      determinations. Lumbar spine bone mineral density was significantly higher in the
      premenopausal women group than in the three postmenopausal groups. Peripheral
      blood monocytes were cultured for 48 h with 20% autologous plasma, and after
      stimulation with lipopolysaccharides. IL-1, IL-6, and TNF alpha levels were
      measured by RIA in the monocyte surpernatants. The three cytokines were highly
      correlated to each other, IL-1 with IL-6 (r = 0.76; P < 0.001), IL-1 with TNF
      alpha (r = 0.89; P < 0.001), and IL-6 with TNF alpha (r = 0.89; P < 0.001). The
      mean levels of the three cytokines could not be compared because of the
      variations in the values. However, a trend toward lower levels in the three
      cytokines was noted in estrogen-treated women compared to the untreated
      postmenopausals. The bone-resorbing activity of monocyte supernatants, assessed
      by fetal long bone-resorbing assay, increased in untreated postmenopausal
      compared to that in premenopausal women (1.22 +/- 0.08 vs. 0.87 +/- 0.11; P <
      0.05). In estrogen-treated patients, this activity decreased to premenopausal
      levels (0.89 +/- 0.04 vs. 0.87 +/- 0.11; P = NS). The resorbing activity was
      correlated to IL-1 (r = 0.28; P = 0.03), IL-6 (r = 0.52; P < 0.01), and TNF alpha
      (r = 0.48; P < 0.01). The addition of cytokine inhibitors and IL-1 receptor
      antagonist and TNF alpha antibodies to the supernatant bone culture medium
      induced a significant decrease in the calcium release. Those data show the
      involvement of several cytokines in the bone resorption process after estrogen
      deficiency.

PMID- 8263154
TI  - Presence of glucagon and glucagon-like peptide-1-(7-36)amide receptors in
      solubilized membranes of human adipose tissue.
AB  - Specific receptors for glucagon and for glucagon-like peptide-1 (GLP-1) (7
      36)amide have been found in solubilized human adipose membranes. The 50%
      inhibition dose of the corresponding unlabeled peptide was near to their
      physiological levels [ID50, 0.5 nmol/L for glucagon and 1.0 nmol/L for GLP-1(7
      36)amide;]. In both cases, the presence of high affinity receptors was evident
      [Kd, 0.5 and 0.7 nmol/L for glucagon and GLP-1(7-36)amide, respectively]; the
      high affinity maximal binding capacity for GLP-1(7-36)amide was higher than that
      for glucagon (893 and 117 fmol/mg solubilized fat membranes, respectively).
      Glucagon at 10(-6) mol/L did not compete with the [125I]GLP-1(7-36)amide binding,
      nor did GLP-1(7-36)amide (10(-6) mol/L) compete with that of [125I]glucagon. The
      relative abundance of GLP-1(7-36)amide receptors in human adipose tissue is
      further support for a direct and probably important action of this peptide in the
      metabolism of the fat cell.

PMID- 8263155
TI  - Cardiac structural and functional abnormalities in adult patients with growth
      hormone deficiency.
AB  - Little information is available on cardiac involvement in GH-deficient adults.
      Thus, we evaluated cardiac structure and function by means of one- and two
      dimensional echocardiography in 11 adult patients [3 women and 8 men; mean age,
      27.2 +/- 3.8 (+/- SD) yr] affected with GH deficiency. Twelve age- and sex
      matched normal subjects served as the control group. All patients had been
      treated with extractive GH over 9 yr, and therapy withdrawal had been performed
      at least 3 yr before entering the study. GH-deficient patients had significantly
      lower values of interventricular septum (7.1 +/- 1 vs. 9 +/- 0.4 mm; P < 0.01)
      and left ventricular posterior wall thickness (6.1 +/- 1 vs. 9 +/- 0.4 mm; P <
      0.01), which resulted in a significantly smaller left ventricular mass index (54
      +/- 11 vs. 85 +/- 15 g/m2; P < 0.001). The left ventricular end-diastolic and end
      systolic diameters did not differ significantly after correction for body area
      surface, whereas ejection phase indices showed lower values, with a fractional
      shortening of 34 +/- 4% vs. 38 +/- 5% (P < 0.05) and an ejection fraction of 59
      +/- 9% vs. 69 +/- 10% (P < 0.05). In conclusion, the results of this study
      demonstrate the involvement of cardiac muscle in patients affected with GH
      deficiency.

PMID- 8263156
TI  - Effect of the serotonin-4 receptor agonist zacopride on aldosterone secretion
      from the human adrenal cortex: in vivo and in vitro studies.
AB  - We have recently shown that serotonin (5-HT) stimulates cortisol secretion from
      human adrenocortical tissue in vitro through activation of 5-HT4 receptors. The
      aim of the present study was to investigate the effect of the 5-HT4 agonist
      racemic zacopride on aldosterone secretion from the human adrenal gland in vivo
      and in vitro. In vivo studies were conducted on 28 healthy volunteers pretreated
      with dexamethasone. The subjects received a single oral dose of placebo, 10
      micrograms zacopride, or 400 micrograms zacopride. Plasma aldosterone levels
      increased significantly within 90 min after the administration of 400 micrograms
      zacopride, remained elevated for 60 min, and gradually returned to the baseline
      within 180 min. In contrast, the administration of 10 micrograms zacopride or
      placebo did not modify the aldosterone concentration. No significant changes were
      observed in renin, ACTH, or cortisol levels. In vitro studies were conducted on
      perifused human adrenocortical slices. Administration of 20-min pulses of
      zacopride (from 10(-11) - 10(-6) mol/L) induced a dose-dependent increase in
      aldosterone secretion. The minimal effective dose was 10(-10) mol/L, and half
      maximal stimulation was obtained with a dose of 7 x 10(-8) mol/L. Zacopride was
      100 times more potent in stimulating aldosterone than cortisol release. Taken
      together, the present data suggest that 5-HT-evoked aldosterone secretion
      involves the activation of 5-HT4 receptors.

PMID- 8263157
TI  - Recurrence of thyrotoxicosis after attack of allergic rhinitis in patients with
      Graves' disease.
AB  - Graves' disease is frequently aggravated during antithyroid drug therapy;
      however, little is known of its aggravating factors. We studied 83 patients with
      Graves' disease who were euthyroid for at least 6 months under antithyroid
      maintenance therapy, and we examined the relationship between thyrotoxicosis
      relapse, attack of allergic rhinitis, and peripheral eosinophil increase. Forty
      one patients showed thyrotoxicosis relapse; of these, 22 (54%) showed peripheral
      eosinophil increase, and 14 (34%) had attacks of allergic rhinitis. In the
      remaining 42 patients without thyrotoxicosis relapse, only 4 (10%, P < 0.001)
      showed an increase in peripheral eosinophils, and only 3 (7%, P < 0.01) had
      allergic rhinitis. Recurrence of thyrotoxicosis was observed with the increase in
      serum levels of TSH-receptor antibodies and increase in eosinophils 2 months
      after the attack of allergic rhinitis. Three patients with seasonal allergic
      rhinitis showed thyrotoxicosis relapse at the same time of year within 2
      consecutive years. Our findings indicate that allergic rhinitis can be an
      aggravating factor of Graves' disease and suggest that the preceding increase in
      peripheral eosinophils can be a predictive indicator of recurrence of
      thyrotoxicosis during antithyroid drug therapy.

PMID- 8263158
TI  - Body composition, bone metabolism, and heart structure and function in growth
      hormone (GH)-deficient adults before and after GH replacement therapy at low
      doses.
AB  - The effects of recombinant GH doses (10 micrograms/kg.day, 3 times a week for 6
      months) lower than those previously used in the treatment of GH-deficient adults
      (GHDA) on body composition, bone mineral content, and heart structure and
      function were investigated in seven (six males and one female, aged 25-27 yr)
      GHDA. They were studied before treatment, after treatment, and 6 months after
      stopping therapy, and findings were compared with those for 20 sex-, age-, and
      body mass index-matched healthy controls. Before treatment, GHDA showed a
      significant reduction in insulin-like growth factor-I levels, an increase in
      bioimpedance and fat mass percentage, a reduction of bone density at both distal
      and proximal sites, a decrease in bone Gla-protein and procollagen III levels,
      and significant cardiac impairment supported by a reduction of left ventricular
      mass index and left ventricular systolic function with decreased fractional
      shortening and rate-adjusted mean velocity of circumferential fiber shortening.
      GH treatment normalized insulin-like growth factor-I levels, body composition and
      echocardiographic findings, but not bone density. Six months after stopping
      therapy, all parameters investigated returned to the pretreatment conditions. Our
      results suggest that prolonged GH deficiency induces alterations in body
      composition and bone metabolism and density, and impairment of cardiac structure
      and function in adult life. GH replacement therapy for 6 months, despite the low
      doses used by us, is able to improve all previously impaired biochemical and
      clinical features, except for bone density. This improvement disappears 6 months
      after the withdrawal of therapy.

PMID- 8263159
TI  - Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in
      humans.
AB  - The inflammatory cytokines, tumor necrosis factor-alpha, interleukin-1 alpha and 
      beta (IL-1 alpha and -beta), and IL-6 can activate the hypothalamic-pituitary
      adrenal (HPA) axis. Tumor necrosis factor-alpha and IL-1 have been tested in both
      experimental animals and humans, but their administration has been limited by
      significant toxicity, mainly severe hypotension. IL-6, on the other hand, has
      demonstrated modest toxicity in animals. We evaluated the ability of recombinant
      IL-6 to stimulate the human HPA axis in patients with cancer and a good
      performance status, who received daily morning sc injections of 30 micrograms/kg
      IL-6 for 7 consecutive days, during the course of a phase I trial. IL-6 caused
      impressively marked and prolonged elevations of plasma ACTH and cortisol on the
      first day and blunted ACTH responses on the seventh day of treatment, perhaps as
      a result of increased baseline cortisol levels. The overall cortisol response,
      however, on the seventh day was of similar magnitude, suggesting that a new
      equilibrium in the feedback regulation of the HPA axis occurs with chronic IL-6
      administration. The toxic effects of IL-6 were modest, suggesting that it might
      be useful for clinical testing of the HPA axis, as an alternative to the insulin
      tolerance test.

PMID- 8263160
TI  - Association between serum interleukin-6 and serum 3,5,3'-triiodothyronine in
      nonthyroidal illness.
AB  - Increased serum concentrations of FFA, bilirubin, and carboxyl-methyl-propyl
      furanpropionic acid, accumulating in chronic renal failure in direct relationship
      with serum creatinine, have all been implicated in the pathogenesis of the low T3
      syndrome during illness. Cytokines may also be involved in the sick euthyroid
      syndrome. In contrast to interleukin-1 (IL-1) and tumor necrosis factor-alpha, IL
      6 is usually detectable in serum during illness and acts as a systemic hormone.
      We studied the association between serum T3 and IL-6 in consecutive hospital
      admissions with a wide variety of medical conditions. Patients were divided into
      group A (T3, > or = 1.30 nmol/L; T4, > or = 75 nmol/L; n = 41), group B (T3, <
      1.30 nmol/L; T4, > or = 75 nmol/L; n = 46), and group C (T3, < 1.30 nmol/L; T4, <
      75 nmol/L; n = 13). Serum IL-6 levels in groups C and B were higher than those in
      group A (median values 59, 39, and 9 U/mL, respectively; P < 0.01). Serum
      creatinine and bilirubin/albumin ratios were similar in the three groups, but the
      FFA/albumin ratio in group C was higher than in group A (P < 0.05). When all
      patients were analyzed together, serum T3 was negatively correlated to serum IL-6
      (r = -0.56; P < 0.001), bilirubin/albumin ratio (r = -0.29; P = 0.004), and
      FFA/albumin ratio (r = -0.21; P = 0.03), but not with creatinine (r = -0.16; P =
      0.11). Stepwise multiple regression resulted in the following equation: serum T3
      = 2.13-0.18ln(IL-6)-0.15ln(creatinine)-0.094ln(bilirubin /albumin) (r = 0.61).
      The variability in serum T3 was accounted for 28% by ln(IL-6), 5% by
      ln(creatinine), and 4% by ln(bilirubin/albumin). FFA/albumin did not contribute
      in this respect. We conclude that the low T3 syndrome in nonthyroidial illness is
      associated with high serum IL-6 levels. However, even when IL-6 is assumed to
      play a causative role, the variation of serum T3 in NTI-patients remains largely
      unexplained.

PMID- 8263161
TI  - Novel expression of functional human chorionic gonadotropin/luteinizing hormone
      receptor gene in human umbilical cords.
AB  - Human umbilical cord contains two arteries and a vein surrounded by Wharton's
      jelly with amnion covering the exterior surface. The cord blood and amniotic
      fluid contain human CG (hCG). Whether hCG can directly regulate cord functions is
      unknown. We now report that human umbilical cords contain a major 4.4-kilobase
      and minor 2.6- and 1.8-kilobase hCG/LH receptor messenger RNA transcripts. The
      cords also contain a 50-kilodalton immunoreactive receptor protein which can bind
      hCG and LH, but not hFSH or hTSH. Rat testis used as a positive tissue control
      contained the same major and minor receptor transcripts and an 80-kilodalton
      receptor protein which can bind [125I]hCG. Rat liver used as a negative control
      contained neither receptor transcripts nor receptor protein. The smooth muscle
      and endothelial cells of umbilical arteries and vein, umbilical amnion, and cells
      in Wharton's jelly contain the receptor transcripts and receptor protein which
      can bind [125I]hCG. The receptor expression was higher in umbilical vessels
      closer to the baby and decreased toward placenta, becoming barely detectable once
      the vessels were inside the placental tissue. In vitro treatment of umbilical
      cords with highly purified hCG resulted in an increase of immunoreactive
      cyclooxygenase-1, cyclooxygenase-2, prostacyclin synthase, and 6-keto
      prostaglandin F1 alpha, little change in thromboxane A2 synthase and a decrease
      of prostaglandin E2 and thromboxane B2 as compared to the controls, indicating
      that the cord receptors are functional. In summary, these novel findings suggest
      that hCG present in cord blood and amniotic fluid may directly regulate the
      vascular tone and quite possibly other functions of human umbilical cord.

PMID- 8263162
TI  - Detection of thyroid hormones in human embryonic cavities during the first
      trimester of pregnancy.
AB  - Transfer of maternal thyroxine (T4) to the human fetus near term has recently
      been demonstrated. We investigated whether maternal thyroid hormone is available
      to the conceptus during the first trimester of pregnancy as well. Transvaginal
      ultrasound-guided puncture of the embryonic cavities was performed during the
      first trimester of pregnancy to obtain coelomic fluid between 6 and 11 weeks, and
      amniotic fluid between 8 and 11 weeks of pregnancy. T4 was found in coelomic
      fluid with mean values (+/- SEM) being 961 +/- 193 pmol T4/L (747 +/- 150 pg/mL).
      Concentrations increased both with gestational age and with rising maternal serum
      T4. Concentrations of 3,5,3'-triiodothyronine (T3) were at least 30 times lower,
      and those of 3,3',5'-triiodothyronine (rT3) four times higher, than coelomic
      fluid T4. Thyroxine and rT3 in amniotic fluid (8-11 weeks) were markedly lower
      than in the coelomic fluid, and T3 was undetectable. These results show that
      maternal thyroxine can cross the placental barrier as early as the second month
      of pregnancy. T4 from the coelomic fluid may reach the embryo via the yolk sac.
      This finding raises the possibility that the increase in maternal T4 occurring
      during the first trimester may be functionally important for the developing
      embryo, when its thyroid is not yet functioning.

PMID- 8263163
TI  - Vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA)
      expression in luteinized human granulosa cells in vitro.
AB  - Vascularization is a prerequisit for corpus luteum formation. Angiogenesis is
      supposed to be regulated by vascular growth factors. Vascular endothelial growth
      factor (VEGF) induces specifically endothelial cell proliferation as well as
      angiogenesis and increases capillary permeability. With this study we demonstrate
      for the first time the presence of VEGF-mRNA in human luteinized granulosa cells
      by Northern blot technique. Granulosa cells were obtained from 11 individual
      patients undergoing ovarian stimulation for in vitro fertilization procedure. Two
      transcripts of VEGF-mRNA at 3.9Kb and at 4.3Kb could be detected in each case.
      Specific transcripts were expressed in different amounts. These results indicate
      that VEGF may promote at least in part vascularization of the human corpus
      luteum.

PMID- 8263164
TI  - Selection criteria for an antimicrobial susceptibility testing system.

PMID- 8263165
TI  - Differentiation of pathogenic Entamoeba histolytica infections from nonpathogenic
      infections by detection of galactose-inhibitable adherence protein antigen in
      sera and feces.
AB  - We determined whether epitope-specific monoclonal antibodies to the galactose
      inhibitable adherence protein (GIAP) of Entamoeba histolytica could be used in an
      enzyme-linked immunosorbent assay (ELISA) to detect antigen in serum and feces
      and differentiate between nonpathogenic zymodemes and the potentially invasive
      pathogenic organisms that require treatment. Overall, 57% of subjects from Cairo,
      Egypt, with symptomatic intestinal amebiasis and 42% with asymptomatic infection
      possessed GIAP antigen in their sera, whereas 4% of uninfected controls or
      subjects with other parasitic infections possessed GIAP antigen in their sera (P
      < 0.001). In subjects from Durban, South Africa, only 6% of uninfected controls
      or those with nonpathogenic E. histolytica infection were positive for GIAP in
      serum, whereas 3 of 4 with asymptomatic pathogenic intestinal infection and 75%
      with amebic liver abscess were positive for GIAP in serum. Fifteen stool samples
      from patients with intestinal amebiasis were available for study; all had a
      positive ELISA result for fecal GIAP antigen. Epitope-specific monoclonal
      antibodies identified 8 of 15 subjects with fecal antigen from pathogenic
      strains. Seven of those eight subjects had adherence protein antigen in their
      sera, whereas none of seven with apparent nonpathogenic E. histolytica infection
      had adherence protein antigen in their sera. In summary, we were able to detect
      E. histolytica adherence protein antigen directly in serum and fecal samples by
      ELISA. The presence of amebic antigen in serum demonstrated 94% specificity for
      pathogenic E. histolytica infection, and amebic antigen is present during
      asymptomatic intestinal infection. In conjunction with antibody detection, this
      method should be very useful in the diagnosis and management of intestinal
      amebiasis.

PMID- 8263166
TI  - Comparison of quantitative cytomegalovirus antigenemia assay with culture methods
      and correlation with clinical disease.
AB  - Blood samples, obtained predominantly from human immunodeficiency virus-infected
      patients and solid-organ and bone marrow transplant recipients, were submitted to
      the clinical laboratory for detection of cytomegalovirus (CMV) and were processed
      by three methods: conventional culture, centrifugation culture, and CMV
      antigenemia assay with monoclonal antibodies (Clonab CMV; Biotest Diagnostic
      Corporation, Denville, N.J.) to CMV antigens. Of 496 blood samples tested, 107
      were positive by one or more methods: 56 were positive by conventional culture,
      27 were positive by centrifugation culture, and 97 were positive for CMV antigen
      (Ag) by the antigenemia assay. Forty-seven samples were positive by the CMV
      antigenemia assay only; in these samples, a mean of 12 Ag-positive cells was
      detected per 200,000 polymorphonuclear leukocytes examined. In contrast, samples
      positive by the CMV antigenemia assay and both culture methods had a mean of 193
      Ag-positive cells, and samples positive by the CMV antigenemia assay and
      conventional culture alone had a mean of 157 Ag-positive cells. In the
      antigenemia assay, paraformaldehyde fixation resulted in superior cell morphology
      when compared with acetone fixation. Use of immunofluorescence staining reduced
      sample processing time and the complexity of reagent preparation in comparison
      with immunoperoxidase staining. Differences in the sensitivities between the
      immunofluorescence and immunoperoxidase staining techniques for detection of
      antigenemia were minor, with discrepant samples showing only one or two Ag
      positive cells. Clinical disease was generally associated with high-level
      antigenemia, but exceptions were noted. The CMV antigenemia test is a rapid,
      quantitative assay that greatly facilitated the rapid diagnosis of CMV infection.
      However, quantitation of antigenemia is labor-intensive, requires processing of
      samples soon after collection, and does not always correlate with clinical
      disease in the individual patient.

PMID- 8263167
TI  - Serologic evidence of canine and equine ehrlichiosis in northeastern United
      States.
AB  - In a retrospective study, indirect fluorescent-antibody staining methods were
      used to detect immunoglobulins to Ehrlichia canis and Ehrlichia risticii in
      canine and equine sera that had originally been analyzed for antibodies to
      Borrelia burgdorferi. Analyses of 60 dog serum specimens collected in Connecticut
      and New York State during 1986 revealed antibodies to E. canis in 7 (11.7%)
      specimens; titration endpoints ranged from 1:40 to 1:320. Three of these dogs had
      anemia. Of the 187 equine serum specimens obtained in Connecticut during 1985 and
      analyzed by indirect fluorescent-antibody staining methods, 17 (9.1%) contained
      antibodies to E. risticii. Maximal antibody titers of 1:1,280 were recorded for
      serum specimens collected from three equids during May and July. We conclude that
      canine and equine ehrlichiosis coexist with Lyme borreliosis in Connecticut and
      the lower Hudson River Valley of New York State.

PMID- 8263168
TI  - Evaluation of four commercially available enzyme immunoassays for laboratory
      diagnosis of Clostridium difficile-associated diseases.
AB  - Four commercial enzyme immunoassays (EIAs) for the detection of Clostridium
      difficile toxin A have recently been developed and marketed (Premier, Meridian
      Diagnostics, Cincinnati, Ohio; VIDAS, bioMerierux Vitek, Inc., Hazelwood, Mo.;
      Tox-A-Test, TechLab, Blacksburg, Va.; and Bartels, Baxter Diagnostics, McGaw
      Park, Ill.). The performances of these EIAs were compared with those of the
      tissue culture cytotoxicity assay and a definition of C. difficile-associated
      disease based on both laboratory and clinical criteria for 329 clinical
      specimens. Two EIAs (Premier and VIDAS) showed good overall agreement (96 and
      95%, respectively) with the cytotoxicity assay. However, they were less sensitive
      (84 and 71%, respectively) than the Bartels (94%) or Tox-A-Test (93%) EIAs. The
      Bartels and Tox-A-Test assays were much less specific, resulting in poor positive
      predictive values (56%) of the two assays when compared with that of the
      cytotoxicity assay. Tox-A-Test had the added drawback of having a significant
      number of indeterminate results (6.4%). These data indicate that the four EIAs
      all have specific shortcomings. When using these EIAs, testing strategies that
      take these shortcomings into consideration should be developed.

PMID- 8263169
TI  - Detection of antibody to recombinant Norwalk virus antigen in specimens from
      outbreaks of gastroenteritis.
AB  - Norwalk virus and other small round-structured viruses are commonly associated
      with outbreaks of gastroenteritis. We used a recently described recombinant
      expressed Norwalk virus (rNV) capsid protein in enzyme immunoassays to
      quantitatively measure immunoglobulin G (IgG) and IgA to Norwalk virus in serum
      pairs from patients involved in outbreaks of gastroenteritis. The outbreaks
      previously were classified, on the basis of the results of a blocking antibody
      assay, as Norwalk virus negative, serologically intermediate, or Norwalk virus
      positive. The rNV IgG assay was more sensitive than the blocking assay for
      detecting IgG to Norwalk virus in serum from patients in all outbreak classes.
      There was 79% concordance between seroconversions detected by the blocking
      antibody assay and those detected by the rNV IgG assay. The rNV IgA assay
      detected seroconversions to Norwalk virus primarily in patients involved in
      outbreaks previously classified as Norwalk virus positive.

PMID- 8263170
TI  - Genomic fingerprinting of Borrelia burgdorferi sensu lato by pulsed-field gel
      electrophoresis.
AB  - A total of 46 Borrelia burgdorferi sensu lato isolates that were isolated from
      patients with Lyme borreliosis and infected animals or were extracted from ticks
      of the genus Ixodes were analyzed. Large restriction fragment patterns obtained
      after cleavage of genomic DNAs with MluI were analyzed by pulsed-field gel
      electrophoresis (PFGE). To eliminate the contribution of plasmid DNA, only
      fragments greater than 70 kb were used for the analysis. The results indicated
      that each of the 14 B. burgdorferi sensu stricto isolates were recognized by a
      band at 135 kbp, each of the 12 Borrelia garinii isolates by two bands (220 and
      80 kbp), and each of the 20 Borrelia afzelii isolates by three bands (460, 320,
      and 90 kbp). Whereas differences in the PFGE patterns among B. burgdorferi sensu
      stricto isolates and B. garinii isolates were noted, B. afzelii isolates were all
      similar. Identification of isolates by PFGE correlates with their belonging to a
      given species within B. burgdorferi sensu lato.

PMID- 8263171
TI  - Accelerated transmission of Lyme disease spirochetes by partially fed vector
      ticks.
AB  - To determine how rapidly Lyme disease spirochetes (Borrelia burgdorferi) can be
      transmitted by partially fed vector ticks (Ixodes dammini), attached nymphs were
      removed from their hosts at various intervals post-attachment and subsequently
      permitted to re-feed to repletion on noninfected mice. We confirm previous
      reports that ticks deposit Lyme disease spirochetes in the skin of their hosts
      mainly after 2 days of attachment. Those that have been removed from a host
      within this interval can reattach and commence feeding. Spirochete-infected
      nymphs that have previously been attached to a host for 1 day become infectious
      to other hosts within another day. Noninfected nymphs acquire infection from
      spirochete-infected hosts within a day of attachment and become infectious to
      other hosts 3 to 5 days later. Virtually all ticks transmitted infection when
      reattaching after first feeding for 2 days. We conclude that partially fed
      nymphal ticks transmit spirochetal infection more rapidly than do ticks that have
      never been attached to a host and that infected ticks become infectious before
      they molt.

PMID- 8263172
TI  - Use of the polymerase chain reaction with a murine model of picornavirus-induced
      myocarditis.
AB  - Enteroviruses are common pathogens responsible for a wide spectrum of systemic
      infections. Conventional diagnosis of these infections relies on the isolation of
      viruses in cell culture and their identification by seroneutralization with
      polyclonal or monoclonal antibodies. Among enteroviruses, coxsackieviruses B have
      been involved as causative agents for viral myocarditis. Most of the time, in the
      case of cardiac pathologies, viral isolation is negative. Molecular biology
      techniques appear to be an alternative to conventional diagnosis and could supply
      evidence for the direct implication of enteroviruses in these severe pathologies.
      In this paper, we describe a murine experimental model of infection with the
      presumed highly cardiopathogenic coxsackie-virus B type 3. A kinetics of
      infection was observed for a period of 31 days, and the classical virological
      markers (viral isolation from feces and heart biopsies, seroconversion) were
      monitored and compared by means of molecular techniques (molecular hybridization,
      polymerase chain reaction [PCR]). In this 31-day period, the detection of
      coxsackievirus B type 3 RNA in the heart was possible only by using two
      successive seminested PCRs. After 9 to 11 days of active viral replication, when
      all other virological markers were negative, positive PCR signals were obtained,
      which supports the hypothesis of a shift to persistent enteroviral infection.

PMID- 8263173
TI  - Population structure of Australian isolates of Streptococcus suis.
AB  - The genetic diversity of 109 isolates of Streptococcus suis, which were recovered
      mainly from Australian pigs, was examined by multilocus enzyme electrophoresis.
      The collection was genetically diverse. Sixty-five electrophoretic types (ETs)
      were recognized, with a mean genetic diversity per enzyme locus of 0.512, or
      0.431 when the number of isolates in each ET was considered. Serotype diversity
      varied, being greatest for isolates of capsular serotype 15 (0.364), and then
      diminishing in the order of serotypes 9, 1, 4, 1/2, 2, 7, and 3 (0.120). On
      average, isolates from these eight serotypes represented 4.13 separate clonal
      groups per serotype. This diversity indicated that serotyping of S. suis for
      subspecific differentiation is not a reliable technique for identifying specific
      strains and is not a good predictor of the genetic background of a given isolate.
      No tendency for isolates recovered from healthy pigs to be genetically distinct
      from those from diseases animals was found, nor were there consistent differences
      between isolates recovered from animals with different disease syndromes
      (meningitis, pneumonia, and septicemia). Danish reference strains of serotypes 1,
      2, and 7 each belonged to one of the same clonal groupings of these types found
      in Australia, but Danish strains of serotypes 3, 4, 6, and 8 and a strain of
      serotype 1 from the United Kingdom were each genetically distinct from the
      Australian isolates. Generally, isolates in the same ET belonged to the same
      serotype, but one ET contained isolates of types 6 and 6/16, and three were made
      up of isolates of types 2 and 1/2. One isolate of serotype 2, which was recovered
      from a human with meningitis, belonged to the same ET as two isolates of serotype
      2 that were recovered from pigs. The human infection was therefore likely to have
      been zoonotic.

PMID- 8263174
TI  - Enzyme-linked immunosorbent assay for serological diagnosis of Nocardia
      brasiliensis and clinical correlation with mycetoma infections.
AB  - We previously identified three immunodominant antigens obtained from a Nocardia
      brasiliensis cell extract and recognized by sera from mycetoma patients (M. C.
      Salinas-Carmona, L. Vera, O. Welsh, and M. Rodriguez, Zentralbl. Bakteriol.
      276:390-397, 1992). In the present work, we obtained a crude extract from a mass
      culture of N. brasiliensis HUJEG-1 and purified two immunodominant antigens, the
      26- and 24-kDa proteins, by using simple physiochemical techniques. With these
      antigens, we developed a conventional solid-phase enzyme-linked immunosorbent
      assay and tested 30 serum samples from mycetoma patients, 29 from tuberculosis
      patients, 24 from a leprosy group, and 31 from healthy individuals. Our results
      show for the first time statistically significant differences in serology among
      these groups. All mycetoma patients with a positive culture for N. brasiliensis
      had absorbance values higher than 0.3. On the other hand, the mycobacterium
      infected patients as well as the healthy individuals all had absorbance values
      below that level. Moreover, we found a close correlation between the clinical
      condition of the mycetoma patients and the anti-26- and anti-24-kDa protein
      antibody concentrations. We therefore propose the use of this assay in routine
      clinical laboratories to confirm the diagnosis of N. brasiliensis infection in
      human mycetoma cases. In addition, the possible application of this assay in the
      serodiagnosis of Nocardia asteroides infection is also discussed.

PMID- 8263175
TI  - Characteristics of CDC group 1 and group 1-like coryneform bacteria isolated from
      clinical specimens.
AB  - Fifteen strains of CDC group 1 coryneform and biochemically similar bacteria were
      isolated from clinical specimens. Of the 15 strains isolated, 11 were derived
      from abscesses and purulent lesions, mostly from the upper part of the body, and
      3 were grown from blood cultures. Nine strains were associated with mixed
      anaerobic but no other aerobic flora. Seven strains exhibited the classical
      biochemical profile of CDC coryneform group 1; however, eight strains were unable
      to reduce nitrate and were called "group 1-like." Other reactions to
      differentiate CDC group 1 and group 1-like coryneform rods include alpha
      hemolysis on human blood agar, fermentation of adonitol, and the presence of
      alkaline phosphatase. Fifteen strains showed marked CAMP reactions on different
      erythrocyte agars. Gas-liquid chromatography of volatile and nonvolatile fatty
      acids as well as cellular fatty acid patterns and the composition of cell wall
      components suggest that CDC group 1 and group 1-like coryneform bacteria do not
      belong to the genus Corynebacterium but possibly to the genus Actinomyces or
      Arcanobacterium. DNA-DNA hybridization studies revealed that group 1 and group 1
      like strains represent different species.

PMID- 8263176
TI  - Genetic heterogeneity of oncogenic human papillomavirus type 5 (HPV5) and
      phylogeny of HPV5 variants associated with epidermodysplasia verruciformis.
AB  - Variants of oncogenic human papillomavirus type 5 (HPV5), specifically associated
      with epidermodysplasia verruciformis, were recognized on the basis of the genetic
      heterogeneity of the E6 open reading frame (ORF). To further evaluate the genetic
      heterogeneity of HPV5, we sequenced the long control region (LCR), the E7 ORF,
      and the terminal parts of the E2 ORF of five previously characterized HPV5
      variants and compared the data with the published HPV5a1 and HPV5b sequences.
      Alignment of the variants showed 140 (7.6%) variable nucleotides of 1,854
      sequenced. Nucleotide substitution rates varied from 3.6% in the E7 ORF to 11% in
      the E6 ORF. By sequencing the variable region encompassing the LCR 3' part and
      the E6 ORF of isolates from six additional epidermodysplasia verruciformis
      patients, we identified three new variants and three already known variants,
      indicating the stability of HPV5 variants. This stability was further
      demonstrated by the identity of isolates obtained years later from benign and
      malignant lesions of three patients. Phylogenetic analysis of the 10 HPV5
      variants distributed them into three groups, tentatively defining subtypes a, b,
      and c. The phylogenetic grouping shows no geographical dependence, a fact that
      may be related to the host restriction that characterizes HPV5 infections. No
      differences in the enhancer potential of the LCR or in the transactivating
      properties of the E2 protein assayed in vitro were observed among HPV5 variants.
      Whether HPV5 variants possess distinct biological properties in vivo remains to
      be determined.

PMID- 8263179
TI  - Quantitation of Giardia cysts and Cryptosporidium oocysts in fecal samples by
      direct immunofluorescence assay.
AB  - The lack of quick, simple, and sensitive quantitative tests has impeded studies
      on infection patterns and treatment of Giardia spp. and Cryptosporidium spp. A
      quantitative direct immunofluorescence assay (FA) using a commercial FA kit was
      developed and evaluated. Recovery rates of the FA for Cryptosporidium oocysts in
      calf feces seeded with 1,000, 10,000, 100,000, and 1,000,000 oocysts per g were
      14.8, 40.8, 84.2, and 78.2%, respectively. Interassay coefficients of variation
      were 10.6 to 47.1%. Recovery rates of the FA for Giardia cysts in feces seeded
      with 1,000, 10,000, and 100,000 cysts per g were 76.4, 96.9, and 89.6%,
      respectively. Interassay coefficients of variation were 7.4 to 22.1%. By
      comparison, recovery rates of Giardia cyst by sucrose gradient flotation were
      only 20.5, 51.2, and 42.9%, respectively. Counts of cysts-per-gram obtained by
      sucrose gradient flotation with samples from calves, lambs, and ewes were only
      49.1 to 54.8% of those obtained by the FA. Zinc sulfate flotation detected only
      36.4% of infections when there were < or = 1,000 cysts per g. The quantitative FA
      offers a useful technique for epidemiological and control studies of these two
      parasites.

PMID- 8263178
TI  - Prevalence of newly isolated, cytopathic small round virus (Aichi strain) in
      Japan.
AB  - Cytopathic small round virus (Aichi strain), isolated from a patient with oyster
      associated gastroenteritis, showed no reaction in the polymerase chain reaction
      method for enteroviruses or in the enzyme-linked immunosorbent assay (ELISA) for
      the five serotypes of astroviruses. Our ELISA was sensitive in detecting the
      Aichi strain antigen in stool samples, but there was no reaction in this ELISA
      with any non-Aichi strains of enteric viruses, with such origins as enterovirus,
      rotavirus, Norwalk virus, calicivirus, or astrovirus. In the ELISA, 13 of 47
      stool samples from adult patients in five of nine oyster-associated
      gastroenteritis outbreaks were positive, but only 1 of 397 pediatric stool
      samples in Aichi Prefecture was positive. The prevalence rate for Aichi strain
      antibody was found to be 7.2% for persons aged 7 months to 4 years. The
      prevalence rate for antibody to Aichi strain increased with age, to about 80% in
      persons 35 years old. On the basis of the results of the present study, it was
      hypothesized that Aichi strain could be a new type of small round virus that
      mainly produces diarrhea in patients in the 15- to 34-year-old age group, 50 to
      76% of whom possess neutralizing antibody.

PMID- 8263177
TI  - Rapid identification of some Leptospira isolates from cattle by random amplified
      polymorphic DNA fingerprinting.
AB  - We compared random amplified polymorphic DNA (RAPD) fingerprinting with cross
      absorption agglutination and restriction enzyme analysis for typing bovine
      leptospires. Using RAPD fingerprinting, we examined a number of Leptospira
      serovars, namely, hardjo genotypes bovis and prajitno, pomona, balcanica,
      tarassovi, swajizak, kremastos, australis, and zanoni, which are likely to be
      isolated from Australian cattle. Each serovar and genotype had a unique RAPD
      profile. Of 26 field isolates of Leptospira, 23 were identified as hardjo
      genotype bovis subtype A, 2 were identified as zanoni, and 1 was identified as
      pomona by RAPD fingerprinting, and their types were confirmed by cross-absorption
      agglutination and restriction enzyme analysis.

PMID- 8263180
TI  - Detection of Mycobacterium leprae nasal carriers in populations for which leprosy
      is endemic.
AB  - In order to better understand the role of Mycobacterium leprae nasal carriage in
      the maintenance of infection reservoirs and transmission of leprosy, we applied a
      polymerase chain reaction (PCR) that detected a 531-bp fragment of the pra gene
      of M. leprae on nasal swab specimens collected through a total population survey
      from individuals living in an area in which leprosy is endemic. Among the total
      tested population of 1,228 people, 7.8% were found to be PCR positive. PCR
      positivity was shown to be randomly distributed among the population for which
      leprosy is endemic. No association was observed between PCR positivity, age, or
      sex. The observed distribution of PCR positivity among households of different
      sizes confirmed the expected values, with the exception of two households, each
      with three people with PCR-positive nasal swab specimens. Although nasal carriage
      does not necessarily imply infection or excretion of bacilli, the finding of
      nasal carriage supports the theory of a disseminated occurrence of M. leprae in
      populations for which leprosy is endemic.

PMID- 8263181
TI  - Role of specific immunoglobulin E in diagnosis of acute toxoplasma infection and
      toxoplasmosis.
AB  - Toxoplasma immunoglobulin E (IgE) antibodies were evaluated in an immunosorbent
      agglutination assay (ISAGA) and an enzyme-linked immunosorbent assay (ELISA) to
      determine their usefulness in the diagnosis of acute infection with Toxoplasma
      gondii. IgE antibodies were not detected in serum specimens from otherwise
      seronegative individuals, individuals with chronic toxoplasma infection, or
      infants without congenital toxoplasmosis. In contrast, they were detected in
      pregnant women who seroconverted during gestation (100% by ELISA, 63% by ISAGA),
      patients with toxoplasmic lymphadenopathy (96% by ELISA, 88% by ISAGA), infants
      with signs of congenital toxoplasmosis which prompted serologic testing in the
      postnatal period (92% by ELISA, 67% by ISAGA), children and adults with
      toxoplasmic chorioretinitis (36% by ELISA, 18% by ISAGA), and adult patients with
      AIDS and toxoplasmic encephalitis (33% by ELISA, 25% by ISAGA). In many of the
      serum specimens, the titer of IgE antibodies detected by the ISAGA were close to
      or at the positive cutoff value. The duration of detectable IgE antibodies in
      patients with acute infections varied considerably among individuals but showed a
      trend toward a briefer duration by the ISAGA than by the ELISA. These results
      reveal that recrudescence of IgE antibodies in patients with reactivated chronic
      infection (toxoplasmic chorioretinitis and toxoplasmic encephalitis) may be
      useful diagnostically and that demonstration of toxoplasma IgE antibodies is a
      useful adjunct to currently available serologic tests for the diagnosis of acute
      toxoplasma infection and toxoplasmosis.

PMID- 8263182
TI  - Life cycle of the human and animal oomycete pathogen Pythium insidiosum.
AB  - Pythium insidiosum, the etiologic agent of pythiosis insidiosii, causes life
      threatening infections in humans and animals. Previous studies of the
      epidemiology of this disease hypothesized about the possible life cycle of this
      oomycete. Details, however, were not provided on the steps required to cause
      infection. We investigated the life cycle of P. insidiosum by inoculating pieces
      of equine skin and plant leaves and then studying the ensuing events with a
      scanning electron microscope. Our observations revealed that zoospores had a
      strong tropism for skin tissue, horse and human hair, and water lily and grass
      leaves and a weak attraction to a variety of other leaves. Encysted zoospores
      were observed on the favored leaves and skin. There they produced germ tubes and
      later abundant hyphal filaments that penetrated leaf tissues. Young sporangia had
      compact, thick walls. The sporangial wall was reduced to a fragile membrane when
      the sporangia had produced well-differentiated biflagellate zoospores. The
      encysted zoospores secreted an amorphous material that permitted the zoospores to
      adhere to skin and plant tissues. On the basis of these findings, a model to
      explain the life cycle of P. insidiosum is proposed.

PMID- 8263183
TI  - Polymerase chain reaction-based strain characterization of noncapsulate
      Haemophilus influenzae.
AB  - A polymerase chain reaction-based typing method for noncapsulate Haemophilus
      influenzae was developed. Randomly amplified polymorphic DNA fingerprints were
      generated from boiled supernatants prepared directly from bacterial colonies
      without the need for DNA extraction. The technique was applied to isolates
      obtained during putative outbreaks of chest infection and validated by comparison
      with sodium dodecyl sulfatepolyacrylamide gel electrophoresis analysis of outer
      membrane protein-enriched preparations and rRNA gene restriction analysis. There
      was complete concordance between the three techniques. The results show that
      randomly amplified polymorphic DNA analysis provides a highly discriminatory
      method of characterizing strains of noncapsulate H. influenzae which is eminently
      suitable as an epidemiological tool for the rapid investigation of outbreaks of
      infection.

PMID- 8263184
TI  - Bactericidal, virucidal, and mycobactericidal activities of reused alkaline
      glutaraldehyde in an endoscopy unit.
AB  - Baths with 2% alkaline glutaraldehyde are often reused for 14 days to
      decontaminate flexible fiberoptic endoscopes (FFEs) between patients, but the
      effect of such reuse on the disinfectant's activity has not been known. Many busy
      endoscopy units also disinfect FFEs with contact times shorter than those
      recommended by the disinfectant manufacturer. We therefore collected samples of
      the disinfectant over the 14-day reuse period from two manual and one automatic
      bath used for bronchoscopes and gastroscopes at a local hospital. Control samples
      were also collected from a manual bath of 2% alkaline glutaraldehyde which did
      not receive any endoscopes. The germicidal activities of the samples were
      assessed in a carrier test against a mixture of hepatitis A virus, poliovirus 1
      (Sabin), and Pseudomonas aeruginosa; the mixture also contained either
      Mycobacterium bovis or Mycobacterium gordonae. Bovine serum (5%) was the organic
      load. The criterion of efficacy was a minimum of a 3-log10-unit reduction in the
      infectivity titers of the organisms tested. The initial disinfectant
      concentration in all the baths was nearly 2.25%; it became about 1.8% in the
      control bath and fell to approximately 1% in the three test baths after 14 days.
      No protein was detected in the control bath, while its concentration rose
      gradually in the test baths to a maximum of 1,267 micrograms/ml after 14 days.
      With a contact time of 10 min at 20 +/- 2 degrees C, all the samples from the
      control bath were effective against all the test organisms and all the samples
      from all the test baths were also effective against P. aeruginosa. With a contact
      time of 10 or 20 min at 20+/-2 degrees C, the virucidal and mycobactericidal
      activities of the samples from the test baths showed broad-spectrum germicidal
      activity when the contact time was increased to 45 min and the temperature was
      raised to 25 degrees C. These findings emphasize the care needed in the
      disinfection of FFEs, especially in view of the increasing threat of AIDS and the
      resurgence of tuberculosis.

PMID- 8263185
TI  - Rapid detection of Streptococcus pyogenes in pediatric patient specimens by DNA
      probe.
AB  - A chemiluminescent DNA probe test (Group A Streptococcus Direct Test; Gen-Probe,
      Inc., San Diego, Calif.) for rapid, direct detection of cRNA of Streptococcus
      pyogenes in throat swabs was compared with conventional culture and
      identification techniques. Throat swabs from 277 patients suspected of having
      streptococcal pharyngitis were examined. By DNA probe alone, 10 specimens were
      positive, 51 were positive by both assays, and 8 were positive by culture alone.
      Thus, DNA probe sensitivity, specificity, and positive and negative predictive
      values were 86, 95, 84, and 96%, respectively. Including an indeterminate
      category, sensitivity, specificity, and positive and negative predictive values
      were 89, 96, 86, and 97%, respectively. After discrepancy testing, these values
      for the raw data improved to 90, 98, 93, and 97%, respectively. None of the 24
      specimens that grew non-S. pyogenes beta-hemolytic streptococci in culture were
      positive by the DNA probe. Because mucoid S. pyogenes strains are more virulent
      than nonmucoid strains, 24 isolates were retrospectively tested with the DNA
      probe to ensure that both types would be detected equally well. Isolates were
      examined in pure cultures as well as mixed with representative normal oral flora.
      There was no statistical difference in detection of any of the four groups. Group
      A Streptococcus Direct Test is a rapid, sensitive, and specific test for S.
      pyogenes.

PMID- 8263186
TI  - Typing of strains from a single-source outbreak of Pseudomonas pickettii.
AB  - Plasmid profiles, genome restriction fragment polymorphisms, carbohydrate
      oxidation-fermentation reactions, methylumbelliferyl substrate hydrolysis
      patterns, antimicrobial susceptibilities, and results obtained with the Biolog GN
      biochemical substrate kit were used to type 19 common-source, but mixed-biotype,
      outbreak strains and one epidemiologically distinct strain of Pseudomonas
      pickettii. Biotyping with conventional and methylumbelliferyl substrates failed
      to distinguish between strains. Plasmid profile testing was found to be
      inconsistent and not reproducible. The Biolog GN kit allowed greater strain
      differentiation than restriction fragment polymorphism did (12 biotypes versus 5
      biotypes); antimicrobial susceptibility testing yielded 4 biotypes, and oxidation
      fermentation tests gave 3 biotypes. Oxidation-fermentation results were
      consistent with restriction fragment polymorphs in all but 1 of the 20 strains
      tested. For ease of typing, comprehensive typeability, and reproducibility,
      oxidation-fermentation tests should be performed initially and followed if
      necessary by restriction fragment polymorph analysis for the elucidation of P.
      pickettii infection outbreaks.

PMID- 8263187
TI  - Norwalk-like viruses: demonstration of genomic diversity by polymerase chain
      reaction.
AB  - A reverse transcription-polymerase chain reaction (RT-PCR) amplification
      procedure was developed for the detection of Norwalk-like viruses in fecal
      specimens. Ninety-nine fecal specimens collected in the United Kingdom and
      containing small round-structured virus particles as determined by electron
      microscopy were tested. They came from 50 outbreaks and 16 sporadic cases of
      viral gastroenteritis. RT-PCR products of the appropriate size for Norwalk virus
      RNA were detected in 15 specimens from three outbreaks, suggesting that viruses
      closely related to Norwalk virus have not been circulating widely in the United
      Kingdom in recent years. From four isolates, the RT-PCR amplification products of
      two genomic regions were sequenced and the degree of genomic variation was
      compared. DNA sequencing of the PCR products revealed strong similarities among
      strains from the United Kingdom (approximately 97% for both regions amplified)
      but significant differences from Norwalk virus (67 to 78%). All of the viruses
      detected by RT-PCR were classified as serotype UK2 by solid-phase immune electron
      microscopy or enzyme-linked immunosorbent assay. These findings provide evidence
      of a genomic relationship between Norwalk virus and serotype UK2 small round
      structured viruses.

PMID- 8263188
TI  - Diagnosis of Chlamydia trachomatis urethritis in men by polymerase chain reaction
      assay of first-catch urine.
AB  - To determine the accuracy of a recently developed polymerase chain reaction (PCR)
      urine assay to detect Chlamydia trachomatis urethral infection in men, we
      obtained urethral swabs and first-catch urine from 365 men attending a sexually
      transmitted diseases clinic. Thirty-three (9%) of the 365 men were infected with
      C. trachomatis as defined by urethral culture. Thirty-two of the 33 men with
      culture-positive urethral swabs also had PCR-positive urine assays. Of 332
      patients with culture-negative urethral swabs, 325 had PCR-negative urine.
      Compared with chlamydia culture of urethral specimens, PCR assay of urine samples
      thus had a sensitivity of 97% and a specificity of 98%. The positive predictive
      value of the urine PCR assay was 82%, and the negative predictive value was 99%.
      Analysis of discrepant results indicated that six of seven PCR-positive, urethral
      culture-negative patients probably had chlamydial urethritis. All six patients
      had symptoms of urethritis and had either a positive urethral swab PCR or a
      positive urine PCR with a different amplification target. After resolution of
      discrepant results, (defining true positives as the 33 culture-positive patients
      and the 6 PCR-positive, culture-negative patients just described), the
      sensitivity and specificity of culture were 85% (33 of 39) and 100% (326 of 326),
      respectively. The revised sensitivity and specificity of PCR were 97% (38 of 39)
      and 99.7% (325 of 326), respectively. We conclude that this urine PCR assay
      provides a highly sensitive, noninvasive alternative method for the detection of
      C. trachomatis urethral infection in high-risk men attending a sexually
      transmitted diseases clinic. This assay could greatly facilitate the testing of
      larger numbers of male patients for chlamydial infection and should be studied in
      other settings.

PMID- 8263189
TI  - Diagnosis of Chlamydia trachomatis endocervical infections by a commercial
      polymerase chain reaction assay.
AB  - We evaluated a prototype polymerase chain reaction (PCR)-based assay for
      Chlamydia trachomatis developed by Roche Molecular Systems to detect endocervical
      infection in women. Of 587 endocervical samples obtained from women attending the
      Harborview Medical Center sexually transmitted diseases clinic, 58 (10%) were
      positive for C. trachomatis by cell culture. Compared with culture, the PCR
      method had a sensitivity of 88% (51 of 58) and a specificity of 99.2% (525 of
      529). The positive and negative predictive values were 92.7% (51 of 55) and 98.7%
      (525 of 532), respectively. After resolution of discrepant results whereby true
      positives were considered to be either culture-positive patients (58 patients) or
      culture-negative patients positive upon PCR analysis using both plasmid- and
      major outer membrane protein-based primers (4 patients), the resolved
      sensitivities of the PCR and culture were 89 and 93%, respectively. We
      subsequently performed a second analysis of 362 women, comparing the proposed
      commercial PCR assay from Roche Molecular Systems with chlamydia cultures. Thirty
      (8%) women were infected with C. trachomatis. Compared with culture, the assay
      had a sensitivity of 60% (18 of 30) and a specificity of 99% (328 of 332). Repeat
      PCR assay done 2 to 5 days later subsequently yielded positive results for 7 of
      11 PCR-negative samples from culture-positive women. We conclude that the Roche
      Molecular Systems PCR assay provides highly specific results compared with
      culture in a high-risk population of women. Further study is needed, however, to
      more clearly define the sensitivity of the PCR assay in detecting endocervical C.
      trachomatis infection in women and to identify factors that may compromise
      sensitivity.

PMID- 8263190
TI  - Sensitive identification of bluetongue virus serogroup by a colorimetric dual
      oligonucleotide sorbent assay of amplified viral nucleic acid.
AB  - A polymerase chain reaction (PCR) procedure coupled to an enzyme-linked
      oligonucleotide sorbent assay (ELOSA; a PCR-ELOSA) identified all 24 serotypic
      variants of bluetongue virus (BTV) without identifying any of six viruses
      belonging to the related epizootic hemorrhagic disease virus serogroup. The PCR
      ELOSA detected 0.01 50% cell culture infectious doses of each serotype of BTV.
      The sensitivity and serogroup-wide specificity of the PCR-ELOSA may enable it to
      replace the more expensive, time-consuming, and biohazardous methods used in the
      identification of BTV.

PMID- 8263191
TI  - Comparison of latex agglutination test with enzyme-linked immunosorbent assay for
      detection of antibody to varicella-zoster virus.
AB  - A new latex agglutination (LA) test (VZVscan; Becton Dickinson, Cockeysville,
      Md.) was compared with an enzyme-linked immunosorbent assay (ELISA) (Varicella
      STAT; Whittaker Bioproducts, Walkersville, Md.) for detection of varicella-zoster
      virus (VZV) antibody. Of 165 samples tested, 126 (76%) were positive by LA, 123
      (73%) were positive by ELISA, and 35 (21%) were negative by both methods. Six
      samples (4%) were LA positive and ELISA negative or equivocal; three samples (2%)
      were ELISA positive and LA negative. However, LA failed to detect seroconversions
      in four adults with varicella in samples obtained 14 to 17 days after the onset
      of rash. These same samples had ELISA values in the high-positive range. In
      addition, the recommended LA screening dilution (1:2) is not supported by
      published data and should be changed.

PMID- 8263192
TI  - Invasive strains of Escherichia coli belonging to serotype O121:NM.
AB  - Ten strains of Escherichia coli isolated from 10 travellers with sporadic
      diarrhea who were returning to Tokyo, Japan, from abroad were found to be of
      serotype O121:NM and were positive in the Sereny test for invasiveness; this
      suggests that this serotype can cause a shigellosis-like illness in humans. The
      E. coli O121:NM strains were positive in the cell invasion test in HeLa cells.
      Analysis of the plasmid content of these strains showed that they contained a
      high-molecular-mass plasmid of 120 to 140 MDa which has been associated with
      invasiveness and were positive in an enzyme-linked immunosorbent assay for
      detection of the virulence plasmid-encoded proteins of Shigella spp. and
      enteroinvasive E. coli.

PMID- 8263193
TI  - Evaluation of new enzyme-linked immunosorbent assay based on a supernatant
      containing Staphylococcus aureus alpha-toxin produced by Bacillus subtilis.
AB  - The gene encoding alpha-toxin from Staphylococcus aureus was cloned into a
      Bacillus subtilis expression vector (pEF 231/alpha-Tox). The protease-deficient
      B. subtilis strain DB 104 transformed with pEF 231/alpha-Tox expressed and
      secreted 5 mg of alpha-toxin per liter into the growth medium. The alpha-toxin
      containing supernatant was diluted 200-fold and used as coating antigen in an
      enzyme-linked immunosorbent assay (ELISA) for serodiagnosis of septicemia and
      endocarditis caused by S. aureus. Paired sera from patients in acute and
      convalescent stages of S. aureus and non-S. aureus infections were used to
      evaluate this ELISA. To evaluate the effectiveness of the crude preparation, the
      results were compared with those of an ELISA based on a commercially available
      alpha-toxin. Similar rises in serum titers were obtained with either type of
      alpha-toxin preparation. This is the first time a crude supernatant without any
      further purification has been used as an ELISA coating antigen. We therefore
      conclude that B. subtilis is a suitable host organism for cheap and simple
      production of prokaryotic recombinant antigens to be used in serodiagnosis.

PMID- 8263194
TI  - Opacification of Middlebrook agar as an aid in identification of Nocardia
      farcinica.
AB  - One hundred twenty seven human isolates of Nocardia asteroides complex were
      identified to the species level by drug susceptibility testing, acetamide
      utilization, thermotolerance studies, studies of arylsulfatase activity, and
      studies of acid production from rhamnose. N. asteroides complex organisms which
      were not identifiable as N. farcinica or N. nova were designated N. asteroides
      sensu stricto. All of the N. farcinica isolates and none of the other isolates
      produced a milky-white opacity surrounding colonies on Middlebrook 7H10 agar.
      This finding may facilitate the identification of N. farcinica.

PMID- 8263195
TI  - Detection of caprine arthritis-encephalitis virus by polymerase chain reaction.
AB  - Detection of caprine arthritis-encephalitis virus (CAEV) infection in goats is
      currently limited to serologic testing or cell culture. We developed a polymerase
      chain reaction (PCR) assay to detect CAEV sequences in peripheral blood
      mononuclear cells (PBMC), synovial fluid cells (SFC), and milk cells (MC)
      obtained from infected goats. Results were positive for 18 of 20 PBMC, 8 of 8 MC,
      and 5 of 5 SFC samples from seropositive goats, whereas 3 of 33 PBMC samples and
      none of 8 MC or 5 SFC samples from seronegative goats were positive. Two of the
      PCR-positive and seronegative goats seroconverted upon follow-up testing 2 months
      later. This PCR assay provides a useful method for detecting CAEV infection in
      goats.

PMID- 8263196
TI  - Multiple stool examinations for ova and parasites and rate of false-negative
      results.
AB  - A mathematical model that shows the relationship between the number of stool
      examinations for ova and parasites and the rate of false-negative results is
      described. An analysis of 1,869 patients with three stool examinations revealed
      various sensitivities for different parasites.

PMID- 8263197
TI  - Relative frequencies of G (VP7) and P (VP4) serotypes determined by polymerase
      chain reaction assays among Japanese bovine rotaviruses isolated in cell culture.
AB  - The relative frequencies of both the G (VP7) and P (VP4) serotypes of 40 bovine
      rotaviruses isolated in cell culture from diarrheic calves in Japan between
      January 1983 and February 1991 were determined by recently developed polymerase
      chain reaction assays. Isolates with G serotype 6 and P serotype 5 (UK-like
      strains) were most frequently found (42.5%) followed by isolates with G6P11
      (17.5%), G6P1 (10%), or G10P5 (10%). Isolates with G10P11 (B223-like strains)
      were least frequently found (7.5%). The presence of various combinations of G and
      P serotypes suggests frequent reassortment in nature among bovine rotaviruses.

PMID- 8263198
TI  - Growth in serum-free medium improves isolation of Chlamydia pneumoniae.
AB  - Infectivity titers were determined for eight Chlamydia pneumoniae strains
      simultaneously grown in serum-free and serum-supplemented cell culture media. Use
      of serum-free medium resulted in a 10- to 50-fold increase in the susceptibility
      of HL cells to chlamydial infection. Comparative primary isolation of a wild-type
      strain also produced higher inclusion counts in a serum-free environment. Serum
      free cultivation is recommended to increase the efficiency of C. pneumoniae
      isolation from clinical material and to permit elementary body purification
      without interference caused by serum components.

PMID- 8263199
TI  - Evaluation of Etest for testing antimicrobial susceptibilities of Neisseria
      gonorrhoeae isolates with different growth media.
AB  - The MICs for 101 isolates of Neisseria gonorrhoeae obtained by Etest (AB-Biodisk,
      Solna, Sweden) and the agar dilution method on GC medium base supplemented with
      1% Kellog's defined supplement (GCMB) were compared. The overall percent
      agreement (within 1 log2 dilution) between methods was greater than 97.9. The
      Pearson's correlation coefficients for penicillin, tetracycline, erythromycin,
      and ceftriaxone for the two methods were 0.98, 0.97, 0.93, and 0.93 (P = 0.001),
      respectively, for comparisons on GCMB. The overall percent agreement was lower
      when hemoglobin-supplemented GCMB was used. Etest is an attractive alternative to
      the agar dilution method for gonococcal antimicrobial susceptibility testing and
      should be further analyzed in multicenter studies.

PMID- 8263200
TI  - Reliability of two novel methods, Alamar and E test, for detection of methicillin
      resistant Staphylococcus aureus.
AB  - E test strips (AB Biodisk, Culver City, Calif.) tested on 2% NaCl-supplemented
      Mueller-Hinton agar and Alamar panels (Alamar, Sacramento, Calif.) correctly
      characterized 127 of 127 methicillin-resistant Staphylococcus aureus isolates and
      100 of 100 methicillin-susceptible S. aureus isolates. These overnight
      antimicrobial susceptibility test systems reliably detect this clinically
      important resistance.

PMID- 8263201
TI  - Ehrlichia chaffeensis and Rochalimaea antibodies in Kawasaki disease.
AB  - Sera from 38 patients with Kawasaki disease were tested for immunofluorescent
      antibodies to Ehrlichia chaffeensis, Rochalimaea henselae, and R. quintana
      Oklahoma. Only 2.5% of the patients tested positive for E. chaffeensis, and 5%
      were positive for R. henselae and R. quintana Oklahoma. Our data suggest that
      Ehrlichia and Rochalimaea spp. do not play a unique role in the etiology of
      Kawasaki disease.

PMID- 8263202
TI  - Laboratory review of reference strains of Corynebacterium diphtheriae indicates
      mistyped intermedius strains.
AB  - All biotyped strains of Corynebacterium diphtheriae from the American Type
      Culture Collection (ATCC) were compared for morphology and biochemical reactions.
      Biotypes of all gravis strains and most mitis strains were confirmed, but
      intermedius strains were found to be misclassified. New lipid-dependent
      intermedius strains have been deposited with the ATCC.

PMID- 8263203
TI  - Direct detection of Escherichia coli Shiga-like toxin genes in primary fecal
      cultures by polymerase chain reaction.
AB  - A single pair of oligonucleotide primers was used for polymerase chain reaction
      amplification of a 212- or 215-bp region of Escherichia coli Shiga-like toxin
      (SLT) genes from crude fecal culture extracts. Genes were typed by hybridization
      of the polymerase chain reaction products to SLT-I- or SLT-II-specific
      oligonucleotide probes. The procedure was capable of detecting fewer than 10 SLT
      producing E. coli organisms per ml of culture against a background of more than
      10(9) other organisms per ml and provides a rapid and sensitive means of
      screening primary fecal cultures for the presence of such strains. When this
      procedure was used to test primary cultures from gut contents or feces from
      various patient groups, including apparently healthy infants, approximately half
      of all samples yielded positive results for SLT-I and/or SLT-II sequences.

PMID- 8263204
TI  - Detection of cholera toxin gene in stool specimens by polymerase chain reaction:
      comparison with bead enzyme-linked immunosorbent assay and culture method for
      laboratory diagnosis of cholera.
AB  - Stool specimens obtained from 123 hospitalized patients with acute secretory
      diarrhea admitted to the Infectious Diseases Hospital, Calcutta, India, were
      examined for isolation of Vibrio cholerae O1 by direct or enrichment plating on
      selective media for cholera toxin (CT) by bead enzyme-linked immunosorbent assay
      (bead-ELISA) and for the CT gene by polymerase chain reaction (PCR). V. cholerae
      O1 was isolated either by direct culture or by enrichment culture from 70 stool
      specimens, all of which gave positive results by PCR. Eleven specimens which were
      culture negative and bead-ELISA positive also gave positive results by PCR. In
      addition, 13 more specimens which were negative by both the culture method and
      bead-ELISA, were positive by PCR. With the combined results of both the culture
      method and the CT bead-ELISA, a confirmed laboratory diagnosis of cholera could
      be made from 81 stool specimens, while the combined results of the three methods,
      including PCR, yielded a positive result for 94 specimens examined. From these
      data, we conclude that PCR provides a more sensitive and specific assay for rapid
      diagnosis of cholera than currently available methods.

PMID- 8263205
TI  - Detection of microsporidian spores in clinical samples by indirect fluorescent
      antibody assay using whole-cell antisera to Encephalitozoon cuniculi and
      Encephalitozoon hellem.
AB  - Three polyclonal mouse antisera, to Encephalitozoon cuniculi, Nosema algerae, and
      Nosema corneum, and two polyclonal rabbit antisera, to E. cuniculi and
      Encephalitozoon hellem, were used in an indirect fluorescent-antibody assay (IFA)
      with Enterocytozoon bieneusi, E. cuniculi, and Encephalitgozoon. hellem spores
      (spores of the last two were taken from culture). Enterocytozoon bieneusi cannot
      be cultured. By IFA, antisera to E. cuniculi and E. hellem reacted strongly and
      equally with each other's spores. The mouse antisera reacted strongly with the
      homologous species, but for these there was segmental and particulate or "dot"
      staining of heterologous microsporidian spores, indicating cross-reactions with
      more selected antigens. In fecal samples, cross-reactions with both mouse and
      rabbit antisera were sometimes seen with different yeast species, with species of
      streptococci, and species of gram-negative rods. There were no cross-reactions to
      staphylococci. Enterocytozoon bieneusi was easily identified in duodenal and
      colonic biopsies, duodenal and colonic fluids, and feces of symptomatic AIDS
      patients by IFA. In a study of 12 AIDS patients with diarrhea, the new IFA
      identified microsporidia in all of 11 fecal samples, three colon fluids, six
      duodenal fluids, and three duodenal biopsy touch preparations. Although the fecal
      sample of 1 of the 12 was negative, the patient's duodenal fluid contained
      microsporidian spores by IFA.

PMID- 8263206
TI  - VP4 serotype of the Gottfried strain of porcine rotavirus.
AB  - The antigenic relationships of the VP4 serotype of porcine rotavirus Gottfried
      strain with other rotaviruses were determined by using antiserum to Gottfried VP4
      baculovirus recombinant. This antiserum failed to react significantly with virus
      of serotypes P1A, P1B, P3, and OSU; however, it reacted with P2 strains. In the
      reciprocal assay, antiserum to VP4 of an asymptomatic strain (P2) failed to
      neutralize the Gottfried strain virus to a significant level. It thus appears
      that the Gottfried strain should be considered a subtype of P2.

PMID- 8263207
TI  - Cefuroxime screening test for pneumococci.

PMID- 8263208
TI  - BACTEC high-blood-volume fungal medium versus Isolator comparison misleading.

PMID- 8263209
TI  - Use of polymerase chain reaction for detection of Chlamydia trachomatis.

PMID- 8263210
TI  - Clinical application of a solid three-dimensional model for orbital wall
      fractures.
AB  - Orbital wall fractures have been diagnosed conventionally by plain X-rays, CT
      imaging, and more recently by three-dimensional CT imaging. However, it is not
      easy to know the three-dimensional appearances of orbital wall fractures.
      Anatomically precise reconstruction of the orbital wall is essential for the
      appearance and function of the eyes. Life-size solid models of fractured orbital
      walls and also solid models of bone grafts for the reconstruction were produced
      by milling polyurethane foam on the basis of CT data. These models are very
      valuable because they provide not only satisfactory understanding of the three
      dimensional morphology, but the models at hand are the ideal guides during the
      operation, and the prefabricated bone grafts, based on the models make a complete
      surgical simulation.

PMID- 8263211
TI  - An audit of 50 bitemporal flaps in primary facial trauma.
AB  - The bitemporal (bicoronal) flap is a well recognised technique for exposing the
      skull and upper face. Prospectively collected data over a 5-year period in which
      this technique was used for access in primary craniomaxillofacial trauma was
      analysed. Emphasis was placed on indications, complications and outcome. A total
      of 50 cases were audited. 84% were male. 74% had sustained midface or frontal
      bone trauma, 24% had lateral upper face injuries. Only 1 patient had a
      penetrating missile injury. Consistent complications of the procedure were
      altered sensation at the vertex in the early postoperative period and a small
      area of wound breakdown over the suture knot in the galea. In all cases the
      altered sensation greatly improved or resolved, 12% developed a wound infection,
      however, 83% of these were trivial requiring no active treatment. There was an
      isolated case of pressure necrosis over a drain site. 12% had a demonstrable
      transient deficit of the temporal branch of the facial nerve, all of which
      improved.

PMID- 8263212
TI  - MR imaging of the TMJ. MR diagnosis and intraoperative findings.
AB  - Magnetic resonance imaging provides the possibility of a non-invasive method for
      the investigation of the soft tissues of the temporomandibular joint (TMJ).
      Between March 1991 and August 1992 we performed static and dynamic magnetic
      resonance images (MRI) on 47 TMJs of 37 symptomatic patients using a MR-tomograph
      with a 6.5 cm surface coil. MR diagnosis could be verified in 15 joints at
      operation and in 3 cases by arthrotomography. Disc position was confirmed in 80%,
      perforations were missed in 2 out of 3 cases and two more perforations became
      obvious during operation. One patient refused MR examination, in 2 cases MRI had
      to be abandoned because of the patient's claustrophobia. In our work we wanted to
      show that MRI is a reliable tool to determine disc position, disc shape and disc
      behaviour during motion. Detection of perforations is still the domain of
      arthrography.

PMID- 8263213
TI  - Maxillofacial fractures in children.
AB  - A clinico-statistical and long-term follow-up study was performed on 81 pediatric
      fractures seen during the 14 years between 1977 and 1990. Of all maxillofacial
      fractures, the incidence of pediatric fractures was 14.7%. The ratio of boys to
      girls was 2.1:1, and the highest incidence involved boys over 13 years of age.
      Fractures of the upper alveolar bone and mandible were common. Conservative
      therapy, such as maxillomandibular fixation using orthodontic brackets was
      usually performed and was found to be successful. The long-term follow-up study
      revealed that 5 out of 21 patients with alveolar fractures complained of
      malocclusion and it is suggested that a longer duration of intramaxillary
      fixation and long-term follow-up might be needed for alveolar fractures in
      children.

PMID- 8263214
TI  - Psammomatoid ossifying fibroma of the paranasal sinuses. An extragnathic variant
      of cemento-ossifying fibroma. Report of three cases.
AB  - Psammomatoid ossifying fibroma (POF) is a diagnostic designation for a sinonasal
      or orbital fibroosseous lesion characterized by numerous small round mineralized
      spherules lying in a fibroblastic stroma. We report 3 cases. One occurred in the
      frontal sinus of an 18-years-old male; 1 in the frontal sinus of a 20-year-old
      male and 1 in the maxillary sinus of a 36-year-old male. Rather limited excision
      resulted in a disease-free follow-up time from 2 to 6 years. The histomorphology
      of POF was compared with other fibro-osseous lesions of the craniofacial skeleton
      including the jaws. It appeared that POF is similar to cemento-ossifying fibroma
      occurring in the jaws and the necessity for different names for lesions only
      differing in their site of occurrence is considered to be at least debatable.

PMID- 8263215
TI  - Symmetrical lipomatosis of the tongue presenting as macroglossia. Report of two
      cases.
AB  - Symmetrical lipomatosis in the oral cavity is extremely rare. Two cases of
      symmetrical lipomatosis presenting as macroglossia are presented. Glossectomy was
      performed in order to reduce the size of the tongue and for diagnosis. Because of
      their multiplicity, non-encapsulation and invasiveness, the lesions were
      diagnosed histopathologically as symmetrical lipomatosis.

PMID- 8263216
TI  - Immediate reconstruction of massive cranio-orbito-facial defects with allogeneic
      and alloplastic matrices in baboons.
AB  - 40 cranio-orbito-facial osseous defects were created in 20 adult male baboons
      (Papio ursinus) to test the effectiveness of an allogeneic and an alloplastic
      matrix implant for the functional and morphological repair of the disassembled
      craniofacial complex. In each animal, one defect was reconstructed with a
      craniofacial bone segment harvested from donor adult baboons, and processed so as
      to obtain autolysed antigen-extracted allogeneic (AAA) bone matrix, preserving
      the bone morphogenetic protein (BMP) activity essential for bone induction. The
      contralateral defect was implanted with spherical macrobeads of
      polymethylmethacrylate (PMMA) coated with poly-2-hydroxyethylmethacrylate
      (PHEMA), and sintered into a porous molded implant, replicating the structural
      anatomy of the avulsed osseous segment. Histological analysis was carried out on
      undecalcified and decalcified bone sections prepared from specimens harvested at
      3, 6 and 12 months after surgery. In AAA bone, the morphogenetic response was
      characterized by vascular invasion and mesenchymal cell aggregation after partial
      resorption of the implanted matrix. This was followed by bone deposition at the
      osteotomy interfaces and within the medullary spaces of the implanted AAA bone.
      Although bone ingrowth did occur in some PMMA/PHEMA specimens, the majority of
      implants showed fibrous union at the recipient interfaces. The limited bone
      ingrowth may be related to narrow interconnections between larger porous spaces
      after chemical synthesis of the two polymeric components. Osteogenesis in AAA
      bone appeared consistent with osteoconductive invasion from the viable bone at
      the recipient interfaces. In addition, the finding of a delicate trabecular-like
      bone, appositional to the central areas of the implanted matrix, suggests bone
      formation by induction.

PMID- 8263217
TI  - Osmotically induced tissue expansion with hydrogels: a new dimension in tissue
      expansion? A preliminary report.
AB  - The possibility of using an osmotically-driven system for effective tissue
      expansion has been verified. As a biocompatible and efficient system, a copolymer
      of methylmethacrylate and vinylpyrrolidone is used in animal research (rats).
      This hydrogel was able to generate, in vitro, a physical swelling pressure of
      approximately 235 mm Hg. The range of possible volume expansion in solutions of
      differing concentrations was 3 to 30 times its water-free gel form. In animal
      experiments a high biocompatibility and efficiency in tissue expansion can be
      observed.

PMID- 8263218
TI  - From behavior theory to behavior therapy: the contributions of behavioral
      theories and research to the advancement of behavior therapy.
AB  - As we approach the latter years of the twentieth century, a century that
      witnessed the birth of the behavior therapy movement, it becomes increasingly
      important to understand the forces that shaped the development, advancement, and
      success of behavior therapy. This paper is an introduction to a series of
      articles analyzing how major behavioral theories and research have contributed to
      the advancement of behavior therapy. In view of the fact that many behavior
      therapists have lost touch with the relation between behavior theory and behavior
      therapy and the challenges of the "cognitive revolution", we argue that the field
      would benefit conceptually and practically from integrating and utilizing the
      resources provided by recent advances in basic behavioral theory and research.
      The articles in this symposium attempt to build conceptual, methodological, and
      practical bridges to help behavior therapists recognize and utilize basic
      behavioral research and concepts.

PMID- 8263219
TI  - Unifying the field: developing an integrative paradigm for behavior therapy.
AB  - The limitations of early conditioning models and treatments have led many
      behavior therapists to abandon conditioning principles and replace them with
      loosely defined cognitive theories and treatments. Systematic theory extensions
      to human behavior, using new concepts and processes derived from and built upon
      the basic principles, could have prevented the divisive debates over whether
      psychological dysfunctions are the results of conditioning or cognition and
      whether they should be treated with conditioning or cognitive techniques.
      Behavior therapy could also benefit from recent advances in experimental
      cognitive psychology that provide objective behavioral methods of studying
      dysfunctional processes. We suggest a unifying paradigm for explaining abnormal
      behavior that links and integrates different fields of study and processes that
      are frequently believed to be incompatible or antithetical such as biological
      vulnerability variables, learned behavioral repertoires, and that also links
      historical and current antecedents of the problem. An integrative paradigmatic
      behavioral approach may serve a unifying function in behavior therapy (a) by
      promoting an understanding of the dysfunctional processes involved in different
      disorders and (b) by helping clinicians conduct functional analyses that lead to
      theory-based, individualized, and effective treatments.

PMID- 8263220
TI  - Behavior therapy and the experimental analysis of behavior: contributions of the
      science of human behavior and radical behavioral philosophy.
AB  - It has been argued that clinical psychologists, including clinical behavior
      therapists, are not aware of or knowledgeable about advances being made in basic
      behavioral research (Marks, Behavioral Psychotherapy, 9, 137-154, 1981). The
      present paper addresses the arguments advanced by clinical and experimental
      psychologists that behavior therapy and cognitive-behavior therapy are moving
      away from their respective ties to the experimental operant laboratory. It is
      argued that there are many areas of mutual interest between basic behavioral and
      clinical research and application. Several major research programs of operant
      psychology are analyzed in order to demonstrate conclusively that advances in
      basic behavioral studies have relevance for application by clinical
      psychologists. Progress in the experimental fields of the quantitative law of
      effect (the matching law), operant/classical interactions, including behavioral
      momentum, modeling and verbal and rule-governed behavior are analyzed.
      Applications of these basic behavioral principles to clinical settings are also
      illustrated. It is concluded that the experimental analysis of behavior can add
      much to the continuing development of a scientifically-based clinical psychology,
      and that mutual interest research in both sub-disciplines of psychology will lead
      to a greater understanding of the causes and conditions of human behavior, as
      well as direct the ability of clinical psychologists to effect meaningful
      behavioral change.

PMID- 8263221
TI  - Commentary: the cognitivist oversell and comments on symposium contributions.
AB  - During the 1980s the behavior therapy movement was infiltrated by cognitivists,
      people who believe that all maladaptive fears are based on wrong beliefs and all
      can be overcome by cognitive correction. This article asserts and defends the
      following propositions: (1) There are numerous maladaptive fears demonstrably
      immune to cognitive correction but removable by deconditioning. (2) These
      conditioning based fears constitute the majority, but there are also some based
      on mistaken beliefs. (3) Proponents of the cognitivist viewpoint have overrated
      the outcomes of cognitive therapy, because they have not realized the fact that
      conditioned anxiety is often inadvertently weakened by simultaneous competing
      emotions (nonspecific therapeutic effects). (4) This overrating led to the
      fiction that cognitive-behavior therapy is behavior therapy's best resource to
      overcome non-psychotic depression, a fiction that was exposed by cognitive
      behavior therapy's inferior performance in the National Institute of Mental
      Health's Collaborative Research Project. (5) There is data to suggest that use of
      the full resources of behavior therapy would have produced notably superior
      results. The commentary concludes with comments on the other contributions to the
      symposium, From Behavior Theory to Behavior Therapy.

PMID- 8263222
TI  - Clomipramine, fluoxetine, and behavior therapy in the treatment of obsessive
      compulsive disorder: a meta-analysis.
AB  - The most common effective treatments for obsessive-compulsive disorder include
      clomipramine, fluoxetine, and exposure-based behavior therapy. A meta-analysis
      was conducted on the results from 25 appropriate treatment studies (1975-1991).
      All three treatments were significantly effective for most of the outcome
      variables (overall severity, anxiety, depression). Exposure was not significantly
      effective for reducing depressed mood. More treatment outcome studies are needed
      before a clearly superior treatment or combination of treatments can be
      statistically determined.

PMID- 8263223
TI  - Problems in the case for psychotherapeutic integration.
AB  - The arguments in favor of therapeutic integration are summarized and evaluated.
      Weaknesses of the position are: (1) the false claim that all therapies are
      equally effective; (2) the lack of a clear and accurate specification of what
      makes a school of therapy "legitimate"; (3) the lack of a clear case for an
      accurate and comprehensive list of common elements across therapies; (4) a lack
      of clarity concerning "clinical strategy"; (5) the incorrect claim that cognitive
      therapy provides a useful and neutral meta-language; (6) inadequate evidence of
      trends toward integration; (7) fallacious reasoning based on these alleged
      trends; and (8) a misunderstanding of the history and philosophy of science.

PMID- 8263224
TI  - The effects of "do", "don't" and "wait" requests training on compliance behavior
      and stimulus generalization.
AB  - Previous implementation of compliance training has involved the use of aversive
      behaviors, as consequents, which bear neither a topographical nor a functional
      relationship to the behaviors under training. The present study explores
      compliance training in which training behaviors, used as consequents, are both
      topographically and functionally identical to the target behaviors. This study
      extends the compliance literature through: (1) an analysis of the effects of
      compliance training in long-term institutionalized mentally retarded adults, (2)
      the investigation of a third response class "Wait" requests, and (3) an
      assessment of stimulus generalization. Findings discussed include (a) the
      treatment effects of compliance training, across response classes, within
      treatment sessions; (b) the spontaneous generalization of treatment effects
      outside the treatment conditions; (c) the collateral effects of training upon
      aggressive outbursts; (d) the heightened potential for the utilization of these
      techniques in long-term care institutions.

PMID- 8263225
TI  - Effectiveness of arousal and arousal plus overcorrection to reduce nocturnal
      bruxism.
AB  - This study investigated the effectiveness of arousal and arousal + overcorrection
      to treat bruxism in a 28-year-old male with a 6-month history of bruxing and a 24
      year-old female with a 3-month history of bruxing. An A-B-A-B-A-BC-A multiple
      baseline design across subjects with follow-ups was used to evaluate the
      effectiveness of the interventions. Results indicated that, although arousal
      reduced the frequency of bruxing in both subjects, it did not completely
      eliminate the behavior. The addition of overcorrection to arousal resulted in a
      complete cessation of bruxing. The discussion focuses on the possible mechanisms
      of action and directions for further evaluation of the combined procedure.

PMID- 8263226
TI  - Topographic organization of rat locus coeruleus and dorsal raphe nuclei:
      distribution of cells projecting to visual system structures.
AB  - Previous reports from this laboratory and elsewhere have provided evidence that
      the locus coeruleus (LC) and dorsal raphe (DR) nuclei are topographically
      organized with respect to their efferent targets. Whereas most of these previous
      studies have focused on relationships between these monoamine-containing
      brainstem nuclei and cerebral cortex, basal ganglia, and limbic structures, they
      have not systematically examined the distribution of LC and DR cells that project
      to multiple structures with common sensory or motor functions. The goal of the
      present study was to characterize and compare the distributions of LC and DR
      cells which project to different visual areas of the rat central nervous system.
      Long-Evans hooded rats received unilateral pressure injections of the retrograde
      tracer wheat germ agglutinin-horseradish peroxidase in either the dorsal lateral
      geniculate, ventral lateral geniculate, or lateral posterior nucleus of thalamus;
      superior colliculus, cortical area 17, cortical area 18a/b; cerebellar vermis
      (lobules VI and VII); or paraflocculus. Transverse sections through the midbrain
      and pons were examined by light microscopy after performing routine tetramethyl
      benzidine histochemical procedures. For all cases studied, retrogradely labeled
      cells were observed throughout the rostrocaudal extent of the LC and DR; however,
      labeling patterns which were distinctive for different injection sites were noted
      in each of these brainstem nuclei. The major conclusion drawn from this work is
      that subsets of LC and DR cells which project to different target structures
      within the rat visual system are found in overlapping but not necessarily
      coextensive zones within these nuclei. These studies provide further evidence of
      a rough topographic ordering within both the LC and DR nuclei, as well as support
      a new hypothesis that the outputs from each of these nuclei are organized with
      respect to the sensory related functions of their efferent targets.

PMID- 8263227
TI  - Differential action of the albino mutation on two components of the rat's
      uncrossed retinofugal pathway.
AB  - The development of the uncrossed retinofugal pathways in normally pigmented and
      albino rats, aged from embryonic day (E) 14.5 to E18.5, was investigated. DiI was
      placed into one optic tract and the retinal origin of the uncrossed component, as
      well as its course in the optic stalk, was studied. The results show that, as in
      the mouse, the uncrossed retinal projection has two components. The first
      component is seen at E15.5 in normally pigmented animals. It develops exclusively
      in the central parts of the retina and is normal in albino littermates. The
      second component, which arises from the peripheral parts of the ventrotemporal
      retina, is seen two days later at E17.5 in all animals but is significantly
      smaller in albinos than in their pigmented littermates. Studies of axons in the
      optic stalk labelled retrogradely with DiI placed in the optic tract indicate
      that the uncrossed axons have no preference for any position in the stalk except
      when they approach the chiasm, where they tend to accumulate at the caudal region
      of the stalk. The uncrossed axons intermingle with the crossed axons along the
      entire length of the stalk. In albino embryos, no obvious difference in the
      prechiasmatic course of uncrossed axons was seen at any age examined. It is
      concluded that the albino mutation in rats affects the late ventrotemporal
      component of the uncrossed pathway selectively. It does not act on the early
      central component. Further, the intermingling of crossed and uncrossed axons in
      the stalk and the apparently unaffected prechiasmatic course of uncrossed axons
      in albinos indicate that the albino gene has its primary action in the retina.

PMID- 8263228
TI  - Light and electron microscopic immunocytochemical localization of PKC delta
      immunoreactivity in the rat central nervous system.
AB  - Protein kinase C (PKC) is one of the major cellular signal transduction systems.
      Since at least nine different PKC isoenzymes have been described, the purpose of
      the present studies was to identify the regional, cellular, and subcellular
      distributions of PKC delta in the rat central nervous system (CNS) by light and
      electron microscopic immunocytochemistry. We have found that PKC delta
      immunoreactivity is present in all major subdivisions of the rat CNS. Within each
      of the subdivisions, PKC delta immunoreactivity is localized to perikarya that
      monitor sensory and motor functions. More specifically, PKC delta is found in the
      olfactory bulb, cerebral cortex, lateral septum, thalamus, vestibular and
      cochlear nuclei, inferior olive, nucleus of the solitary tract, cerebellum, and
      superficial layers of the dorsal horn in the spinal cord. In most cases, the
      distribution of this isoenzyme is distinct from that of the conventional
      isoforms. Within the CNS, PKC delta is localized primarily in neurons; however,
      neurons of the same type are not uniformly labeled. This is most evident in the
      cerebellum, where alternating columns of Purkinje cells are immunostained. While
      PKC delta is prominent in perikarya, occasional immunostaining is seen in
      dendrites, fibers or axons, and nerve terminal. Electron microscopic analysis of
      the posterolateral nucleus of the thalamus reveals that the cell nucleus, the
      rough endoplasmic reticulum, and the plasma membrane are all immunopositive.
      Since each of the PKC subspecies may have different substrate, lipid, and other
      co-factor requirements, the regional, cellular, and subcellular distribution of
      each of these isoforms should help to define their functional environments.

PMID- 8263229
TI  - Postnatal development of the cholecystokinin innervation of monkey prefrontal
      cortex.
AB  - Although the structure and function of primate prefrontal cortex undergo
      substantial modifications during postnatal development, relatively little is
      known about the maturation of neurotransmitter systems in these cortical regions.
      In the primate brain, cholecystokinin is present in the greatest concentrations
      in prefrontal regions. Thus, in this study, we used immunohistochemical
      techniques to investigate the postnatal development of the cholecystokinin
      innervation of monkey prefrontal cortex. In animals aged 4 days through adult,
      cholecystokinin immunoreactivity was present in nonpyramidal neurons that
      appeared to represent at least two distinct cell types. The most common type was
      a vertically oval bitufted neuron, located in layers II-superficial III, which
      typically had a radially descending axon that gave rise to short collaterals in
      layer IV. Another frequently observed cell type was a larger multipolar neuron
      located in the superficial half of layer III. The axon of these neurons branched
      locally in the vicinity of the cell body. The greatest density of cholecystokinin
      containing neurons and processes was present in monkeys less than 1 month of age.
      The density of immunoreactive structures in every prefrontal region then
      progressively declined with increasing age, with the most marked changes
      occurring during the first postnatal year. As a result, the density of labeled
      neurons in adult monkeys was less than one-third of that in neonatal monkeys.
      However, labeled structures were significantly more dense in some ventromedial
      and orbital regions than in dorsal regions of the prefrontal cortex in neonatal,
      but not in older animals. In all animals, cholecystokinin-containing neurons were
      present in highest density in layers II-superficial III, and labeled terminal
      fields were observed in layers II, IV, and VI. In animals less than 1 month of
      age, fascicles of radial fibers traversed through layers III and V, whereas in
      animals 1 to 3 months of age, individual radial fibers rather than fiber bundles
      were present in layers III and V. In addition, immunoreactive pericellular
      arrays, which appeared to surround unlabeled nonpyramidal cells, were present in
      layers V and VI and the subcortical white matter in the youngest monkeys.
      Although many aspects of the cholecystokinin innervation of monkey prefrontal
      cortex remain constant during postnatal life, the distinct developmental changes
      in the cholecystokinin innervation of these regions suggest that it may play an
      important role in the maturation of the cortical circuitry that mediates the
      acquisition of certain cognitive abilities.

PMID- 8263230
TI  - Cytoarchitecture, fiber connections, and ultrastructure of the nucleus
      pretectalis superficialis pars magnocellularis (PSm) in carp.
AB  - The cytoarchitecture, fiber connections, and ultrastructure of the nucleus
      pretectalis superficialis pars magnocellularis (PSm) were studied in cypriniform
      teleosts (Cyprinus carpio). The PSm is an oval nucleus in the pretectum. Medium
      sized cells and synaptic glomeruli are the main components of the nucleus. A
      lesser number of small cells are also present. Most of the medium-sized cells
      form one or two cell layers on the periphery of the nucleus, and some cells are
      scattered among synaptic glomeruli in the nucleus. Cell bodies in the peripheral
      cell layer are pyriform and sprout a thick dendrite directed inward. The dendrite
      gives off fine dendritic branches, which are postsynaptic elements in synaptic
      glomeruli. The PSm projects to the ipsilateral corpus mamillare (CM) and sends
      collaterals to the ipsilateral nucleus lateralis valvulae (NLV). Axons of the PSm
      neurons have terminals with many varicosities in the CM, and collaterals in the
      NLV have cup-shaped terminals around the cell bodies of the NLV neurons.
      Following horseradish peroxidase (HRP) injections into the PSm, HRP-labeled cells
      are found ipsilaterally in the optic tectum, the nucleus tractus rotundus of
      Schnitzlein, and the nucleus ruber of Goldstein. The tecto-PSm projections are
      topographically organized. The rostral optic tectum projects mainly to the
      rostral portion of the PSm, and the caudal tectum projects to the caudal portion
      of the PSm. The ventral tectum sends fibers mainly to the ventral part of the
      PSm. The dorsomedial tectum projects to the medial part of the PSm, and the
      dorsolateral tectum projects to the lateral part of the PSm. Tectal projection
      neurons to the PSm are of only one type. The tectal cell body is pyriform and is
      situated in the superficial part of the ipsilateral stratum periventriculare
      (SPV). The tectal neurons have a long perpendicular dendrite, which branches out
      in the stratum opticum (SO). An axon emerges from the branching site in the SO.
      Judging from the dendritic branching pattern of the tectal projection neurons, we
      concluded that the PSm receives visual information from the optic tectum.

PMID- 8263231
TI  - Neuropeptide Y immunoreactivity identifies a group of gamma-type retinal ganglion
      cells in the cat.
AB  - Ganglion cells within the cat retina have been traditionally grouped by
      morphological criteria into three major classes: alpha, beta, and gamma. The
      gamma-type cells have been least well characterized, but the available evidence
      indicates that this class comprises a relatively heterogeneous population of
      neurons. In the present study we demonstrate that an antibody for neuropeptide Y
      (NPY) recognizes a subpopulation of about 2,000 gamma-type ganglion cells. The
      NPY-immunoreactive (IR) neurons project to the superior colliculus and to the C
      layers of the lateral geniculate nucleus as demonstrated by retrograde labeling
      with fluorescent tracers (fluorogold or rhodamine latex microspheres). Virtually
      all of these cells disappear following lesions of the optic nerve. The NPY-IR
      ganglion cells were identified as gamma cells on the basis of soma size and
      dendritic branching patterns. The somas of these neurons are small (8-22 microns
      in diameter), and each cell is characterized by sparsely branching dendritic
      processes, usually extending into the middle third of the inner plexiform layer,
      the physiologically defined ON sublamina. These neurons are distributed across
      the entire retina, with the highest density at the area centralis. Within local
      regions of the retina, however, there was no indication that the NPY-IR gamma
      cells are arrayed in a regular mosaic pattern. These results provide the first
      evidence that the gamma class of ganglion cells of the cat retina can be
      subdivided on the basis of immunocytochemical properties.

PMID- 8263232
TI  - Integrating primary oral health care into primary care.
AB  - Despite increasing national attention and emphasis on primary health care, there
      has been little impetus to define or specify the content of primary oral health
      care. This paper defines primary oral health care and the scope of services it
      includes, using an adaptation of a Health Resources and Services Administration
      definition of primary health care and its attributes as its model. The proposed
      scope of services encompassed by primary oral health care is a set of basic
      dental services used by the Indian Health Service. Policy recommendations are
      presented to improve the integration of primary oral health services with primary
      health care and primary health care delivery.

PMID- 8263233
TI  - The oral health burden in the United States: a summary of recent epidemiologic
      studies.
AB  - The nation's health care system is currently under scrutiny. A topic of great
      interest to the dental community is whether dentistry should be included in a
      plan for national health reform, and if so, what procedures should be covered. To
      answer this question, 1) the current oral disease burden in the United States
      should be assessed, and 2) factors associated with this burden should be
      described. This paper reviews several recent large-scale epidemiologic surveys of
      oral health in the United States, summarizes their major findings, outlines
      important risk factors for oral disease, and makes recommendations regarding
      future oral epidemiologic surveys. The discussion is limited to the following
      conditions: dental caries, periodontal diseases, tooth loss, edentulism, oral
      cancer, and orofacial clefts. Five out of six 17-year-olds have at least one
      decayed, missing, or filled tooth surface (DMFS), with a mean of eight DMFS per
      17-year-old. However, 25 percent of the country's children have 75 percent of the
      dental caries; minority children, rural dwellers, those with minimal exposure to
      fluoride, and those from less educated or poorer families tend to have a greater
      caries experience. Root caries, gingivitis, periodontal pockets, and loss of
      periodontal attachment are more common among older individuals. Whites have more
      teeth than do Blacks of similar ages, and edentulism is more common among those
      with less education and income. Of those age 65+, over 40 percent are edentulous
      and only 2 percent have all 28 teeth. An estimated 30,000 new cases and 8,000
      deaths were attributed to oral cancer in 1991, with Black males having higher
      incidence and mortality rates than other subgroups. Oral clefts occur in about
      one in 700 total births, with Native Americans having the highest incidence.

PMID- 8263234
TI  - The primary dental care workforce.
AB  - With health care reform at the forefront of our nation's policy agenda, an
      assessment of the current status of the dental primary care workforce is required
      as an essential reform component. There has been much written in the literature
      about manpower but relatively little about the primary dental care workforce. The
      purpose of this paper is three-fold: 1) to describe the current primary dental
      care workforce; 2) to identify the distribution of this workforce; and 3) to
      describe the current delivery system. Characteristics, distribution, and delivery
      systems of the primary dental care workforce in the private and public sectors
      are described, and workforce issues relevant to health care reform are identified
      for future discussion.

PMID- 8263235
TI  - Implications of access, utilization and need for oral health care by the non
      institutionalized and institutionalized elderly on the dental delivery system.
AB  - Oral health is integral to an older adult's general health and quality of life,
      and basic oral health services are an essential component of primary health care.
      The elderly should receive special consideration in terms of their oral health
      care needs since they: 1) may have unique problems accessing the health care
      delivery system; 2) experience different patterns and prevalence rates of oral
      diseases; and 3) may have characteristics that affect the amount and types of
      dental treatment and the method by which it is performed. Older adults are
      maintaining their natural teeth into their later years, and epidemiologic trends
      suggest the increasing need for dental services by older adults. Yet dental
      utilization rates are lower for older adults than for younger age groups, and
      barriers to care include the cost of dental care, the lack of perceived need for
      care, transportation problems, and fear. Oral diseases and impairments are most
      commonly experienced by those segments of society least able to obtain dental
      care. Economically and socially disadvantaged older adults and the physically
      impaired are more likely to experience tooth loss and edentulism, untreated
      dental decay and periodontal diseases. Adults over the age of 65 years have the
      lowest proportion of dental expenses reimbursed by private dental insurance (10
      percent), and the highest percentage of out-of-pocket dental expenses (79
      percent), as compared to all other age groups. Of the two largest public
      programs, Medicare does not pay for most dental services, and Medicaid (Title
      XIX), does not offer dental benefits for adults in most states. Although the
      majority of older adults live independently in the community, there is a growing
      number of elders with special needs that require long term care either at home or
      in an institution. These frail and functionally dependent elders have significant
      dental needs, and experience greater barriers to receiving dental care as
      compared to the independent elderly. Additional research is needed to accurately
      characterize the oral health status and needs of the growing number of homebound
      and institutionalized elders. This will be of growing importance with the
      emergence of the vast array of home health care services available to older
      adults, and the changing emphasis on home care often seen as the preferred and
      lower cost alternative to nursing home care.

PMID- 8263236
TI  - Implications of access, utilization and need for oral health care by low income
      groups and minorities on the dental delivery system.

PMID- 8263237
TI  - The association of oral status with systemic health, quality of life, and
      economic productivity.
AB  - It is well established that many systemic adverse health conditions have
      manifestations in the oral cavity. The purpose of this paper is to summarize the
      available scientific evidence that describes the opposite effect, how adverse
      oral health conditions affect three aspects of daily living: 1) systemic health,
      2) quality of life, and 3) economic productivity. Examples of oral health
      affecting systemic health include rheumatic fever patients who develop infective
      endocarditis from oral bacteria and organ transplant patients who develop severe
      complications from oral infections. Both systemic health and quality of life are
      compromised when edentulousness, xerostomia, soft tissue lesions, or poorly
      fitting dentures affect eating and food choices. Conditions such as oral clefts,
      missing teeth, severe malocclusion, or severe caries are associated with feelings
      of embarrassment, withdrawal, and anxiety. Oral and facial pain from dentures,
      temporomandibular joint disorders, and oral infections affect social interaction
      and daily behaviors. The results of oral disorders can be felt not only
      physically and socially but also economically in our society. Dental disease
      accounts for many lost work and school days. Lower wage earners and minorities
      are disproportionately affected. Although there are many studies that evaluate
      these relationships, most are case reports, cross-sectional studies, or studies
      restricted to small or unique population groups. Lack of standardized
      measurements make comparisons across studies difficult. More population-based and
      longitudinal studies are needed to better understand the nature of these
      relationships.

PMID- 8263238
TI  - Factors to be considered in estimating the cost of dentistry in a national health
      program.

PMID- 8263239
TI  - The quality of life of disabled people.

PMID- 8263240
TI  - Spousal separation and its impact on women's mental health: a study of Japanese
      corporate transfers.
AB  - Marital separation in Japan usually occurs as a result of husbands' occupational
      transfers. There is an increasing number of married men who are transferred by
      their employers and who do not take their families, primarily in order to
      maintain educational continuity for the children. An exploratory field study was
      conducted in which the question was posed: How do women experience their lives
      while their husbands are transferred elsewhere in Japan? The grounded theory
      approach was used to answer the question, with a sample of 28 informants. The
      analysis of interview data revealed a core variable of 'maintaining harmony
      during separation' which described the meaning of the informants' life
      experience. The grounded theory was comprised of five major categories that
      described coping behaviours of wives while their husbands were transferred within
      the country and abroad on a long-term basis. Implications for mental health and
      family nursing are discussed, as well as the implications of the findings for
      social policy makers.

PMID- 8263241
TI  - Women in the 'developing world' and their perceptions of health: an area for
      examination by the nurse from the 'developed world'.
AB  - The aim of this paper is to consider how nurses from the 'developed world', in
      this instance Great Britain, may assist women from the 'developing world',
      specifically from Pakistan, to meet their and others' health needs. To explore
      nurses' understanding of women from Pakistan and its translation into delivery of
      nursing care, a number of topics require exploration. These include culture,
      health, origins of Pakistani women who have settled in Britain, clarification of
      the geographical area under discussion and a brief introduction to two studies
      that have investigated the health beliefs of communities in Pakistan, in
      particular the health beliefs of women. Appreciation of studies that illustrate
      women's beliefs about health can provide a basis upon which further examination
      can take place. Ideas can then be assimilated into a framework for nursing care
      centred around anthropological and holistic approaches to women from Pakistan.
      The outcome of this should be an examination of women's beliefs within a cultural
      context in relation to nursing care and management.

PMID- 8263242
TI  - Spousal caregiving following institutionalization: the experience of elderly
      wives.
AB  - A large body of research reveals the contribution of families to the care of
      elderly and health-impaired community-dwelling individuals. Less is known about
      the contribution of families to the provision of care following the admission of
      elderly relatives to a long-term care institution. Still less is known of the
      experience of elderly wives following the institutionalization of their husbands.
      The purpose of this paper is to increase nurses' awareness, through a review of
      the literature on family caregiving in later life, of the contribution to care
      made by elderly wives following the institutionalization of their husbands. We
      also hope to provide direction for clinicians with respect to the needs and
      concerns of wives, particularly at the time of, and following, the admission of
      their husbands to long-term care institutions.

PMID- 8263243
TI  - Depression during the female climacteric period.
AB  - The paper draws attention to the increased incidence of clinical depression
      reported during the climacteric period of the female life continuum. It seeks to
      identify factors which may be responsible for this phenomenon, drawing upon
      research and anecdotal evidence from both the biological and social sciences.
      With this aim, changes during the climacteric period for women are examined
      within a bio-psycho-social framework. Nursing care and treatment of those
      suffering depression within this stage of the middle years are discussed briefly
      and the influence of personal beliefs, held by both the patient and clinician,
      emphasized. The relevance and importance of these factors when employing the Roy
      Adaptation model in the care of such clients is also considered. In conclusion,
      the author stresses the need for a holistic approach and highlights the value of
      Roy's model in care provision for this patient group.

PMID- 8263244
TI  - Feminism: a concept analysis.
AB  - The purpose of this paper is to analyse the concept of feminism in order to
      clarify a sociological concept for its use in nursing theory and practice. This
      analysis is carried out using the Walker & Avant (1988) model. It includes: a
      literature review, an overview of the uses of the concept drawn from the
      literature, the defining attributes and the justification of their choice, the
      cases to demonstrate the concept, and the concept criteria. The concept was
      chosen out of an interest in developing a feminist nursing theory and desire to
      enhance nursing practice. The literature search proved most fruitful in the
      sociological literature. The nursing sources were fewer and concerned with
      practice rather than articulating any feminist nursing theory. Many of these
      sources were sociologists and nurses. The concept of feminism was defined as the
      concern with gender equality and the promotion of equal rights for men and woman,
      the expression of these concerns through theory or action, and the valuing of
      individuals for their contributions to society rather than their biological or
      sexual characteristics or roles. Although the concept of feminism was defined and
      analysed within the model suggested by Walker & Avant, the author found that the
      concept became oversimplified, losing much of the richness of the literature. The
      author felt that, for any development of theory or practice, this analysis would
      have to be expanded. It is argued that their model is too restrictive as it is
      based on positivist philosophy which seeks to establish divisions where, in fact,
      there is a blurring of meaning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263245
TI  - A deconstruction of caring.
AB  - This paper presents the argument that much of the current focus on caring in
      nursing is misdirected in that it is aimed at explaining a complex process with
      conceptual similarities to teaching, in terms of behavioural categories and
      structures. It is asserted that a pervasive use of the word 'caring' as
      synonymous with nursing has contributed to an erroneous emphasis in general
      nursing on emotional caring. This reflects a dualist notion of physical and
      emotional care, operationalized as separate nursing activities. The growing
      association of nursing with caring is thought to reinforce a fallacious
      distinction between caring and curing which has particularly impeded the
      development of a truly psychotherapeutic role for psychiatric nurses. It is
      concluded that nursing skills will be neither elucidated by further analysis of
      the concept of care nor promulgated by the connotations of the word.

PMID- 8263246
TI  - The determinants of psychiatric nursing practice: a comparison of sociological
      perspectives.
AB  - This paper commences by observing that psychiatric nurses tend not to interact
      with their clients in a therapeutic fashion. It is not clear, however, whether
      this is due to the nature of psychiatric institutions or to the attitudes of
      individual nurses. Contrasting social theories which posit either the importance
      of social structures, or of individual interpretations as determinants of
      behaviour, are outlined. These are then applied to the problem of psychiatric
      nursing practice. It is argued that while there are strengths in both theoretical
      positions, neither on their own can adequately characterize the complexity of the
      problem. Rather than attempting to explain influences upon psychiatric nursing
      practice in terms of either structure or action, we should appreciate the
      importance of, and relationship between, both factors. Given the rapid changes
      occurring in mental health nursing, research into factors influencing practice
      will become increasingly important. In order to explain developments adequately,
      researchers will need to take account of the duality of structure and action.

PMID- 8263247
TI  - Nurses' attitudes towards primary health care: development of an instrument.
AB  - In many countries nurses are the largest group of professionals providing health
      care. If health care is to be provided following a primary health care
      philosophy, nurses must be among the leaders in making the change in the way
      health care is delivered. To be effective nurses must develop positive attitudes
      towards primary health care and incorporate its principles into practice. The
      purpose of this paper is to present the development and testing of an instrument
      to measure nurses' attitudes towards primary health care. The instrument has 35
      items divided into five domains based on the principles of primary health care.
      Two scales, one for attitude and one for importance of concept of professional
      role, are scored on six-point Likert scales. Initial psychometric evaluation
      resulted in alpha coefficients of 0.07 to 0.58 for the domains; 0.70 for the
      attitude scale and 0.93 for the importance scale. Details are provided on the
      measures taken to establish validity of the instrument. Plans for future testing
      are included.

PMID- 8263248
TI  - The knowledge base of health visitors and district nurses regarding products in
      the proposed formulary for nurse prescription.
AB  - The background to the legalization of nurse prescribing is reviewed and a small
      questionnaire survey of health visitors and district nurses described.
      Significantly more district nurses than health visitors wanted to become nurse
      prescribers. Health visitor knowledge of some parasiticidal lotions and
      antifungal agents was found to be variable and the recommended dose of
      paracetamol for post-immunization pyrexia was recognized by less than two-thirds
      of the sample. District nurse knowledge of lactulose was limited in comparison to
      their knowledge of alginate and hydrocolloid dressings; however, their knowledge
      of factors other than dressing type which enhance or delay healing was variable.
      The mean knowledge scores of both the health visitors and district nurses were
      unacceptably low for prescribing purposes. The majority of the total sample
      stated that they would like further training, with a preference for such
      provision in the form of study days.

PMID- 8263249
TI  - A complementary therapy approach to the management of individual stress among
      student nurses.
AB  - This paper examines the difference between qualitative and quantitative research
      approaches and applies the debate to assessing student nurses' stress coping
      styles. In particular, it looks at the value of the qualitative approach as a
      means of appreciating the individual nature of the stress experience. A pilot
      study was conducted among a small group of Project 2000 students. The results
      illustrate that a flexible model which appreciates the differences in individual
      perception is a successful way of enabling students to handle negative stress.
      The paper also reports on a new concept called Determination and the Hypnotic
      Interaction model which enables student nurses to utilize determined experiences
      from previous times and apply them to present and future negative stress. The
      model utilizes a wide range of complementary therapy approaches including
      relaxation, imagery and hypnosis, to enable students to appreciate positive
      stress and to discover and use their natural resources of determination to deal
      with negative stress.

PMID- 8263250
TI  - Australian registered nurse medical device education: a comparison of life
      sustaining and non-life-sustaining devices.
AB  - Registered nurses are primarily responsible for the use of medical devices in
      direct patient care. This cross-sectional survey compared how and what 139
      registered nurses working in a variety of wards/units in a 1000-bed tertiary care
      hospital in South Australia initially learned about the life-sustaining and non
      life-sustaining medical devices they use. Furthermore, the consequences of device
      use both for patients and staff were explored. How and what registered nurses
      initially learned about life-sustaining and non-life-sustaining devices were
      remarkably similar. Consequences of device use, which included increased or
      decreased quality of care, increased nurse stress and patient harm, were related,
      in part, to knowledgeable and proficient device use. Thus, device education for
      nurses is essential and warrants further exploration.

PMID- 8263251
TI  - An evaluation of comparative strategies for teaching breast self-examination.
AB  - This study compared the effects of three alternative methods of breast self
      examination (BSE) instruction (booklet, film and group discussion, individual
      teaching) on nurses' personal BSE practice. A pre-test and follow-up
      questionnaire were administered to a convenience sample of 166 nurses from
      Western Australian hospitals. The results demonstrated that each method of BSE
      instruction produced a significant improvement in the technique of BSE (P <
      0.0001). However, the nurses involved in the film and discussion had the greatest
      improvement in BSE proficiency. Findings were analysed in terms of the Health
      Belief Model. The variables 'barriers to action' and 'perceived susceptibility'
      (in this case, to breast cancer) were found to be predictive of BSE practice;
      'perceived barriers' at pre-test and 'perceived susceptibility' at follow-up. The
      incidence of BSE was significantly higher in the older nurses. A reminder to
      practise BSE was significantly associated with an effective BSE technique.
      Implications for nursing practice are discussed.

PMID- 8263253
TI  - Specialism in nursing: the case of nursing care for elderly people.
AB  - Is elderly care nursing a specialty? This paper reports results from an interview
      based study which aims to uncover the distinctive elements of nursing work with
      elderly people. Within the context of sociological literature on specialism it is
      concluded that a case for seeing elderly care nursing as a specialty area can be
      made. However, that case has implications for the continued marginalization of
      elderly people in society.

PMID- 8263252
TI  - Learning disability nursing: from normalization to materialism--towards a new
      paradigm.
AB  - For almost 2 decades the 'normalization principle' has provided the dominant
      paradigm for the planning and evaluation of nursing services to people with a
      learning disability within the United Kingdom. This has reflected the
      international influence of this philosophy in services to a wide range of
      disadvantaged and marginalized groups. However, this paper will argue that nurses
      working with this client group are facing a range of social and political changes
      which expose the weaknesses in this paradigm. This calls for a new approach to
      the way the relationship between practitioners and their clients is
      conceptualized. Here it is argued that a materialist paradigm provides a more
      realistic framework upon which to base future nursing practice.

PMID- 8263254
TI  - A study of consumer-defined need amenable to community nursing intervention.
AB  - This paper describes the first stage of a research project investigating unmet
      needs for community nursing services. The research analyses the relationships
      between differences in perception of valid needs between the public and staff,
      ways of working and organizational constraints on community nursing practice, and
      the incidence and nature of consumer-defined unmet needs. The aim of the first
      stage was to analyse the level and kind of consumer-defined need amenable to
      community nursing intervention and identify possible shortfalls in current
      provision. The study used a postal questionnaire and samples were selected using
      proportional, stratified random sampling from a Community Health Index. The
      sample size was 1770 and the response rate 38%. Analysis involved frequency
      counts for all variable data and statistical analysis of relationships between
      variables, using the chi-square test with the level of significance set at 5%.
      Analysis of the questionnaire identified possible latent need in relation to
      activities of daily living and health problems. The 57-69 and 70+ age groups were
      found to have the highest level of self-perceived difficulties with the above,
      many of which were said to be unmet. Fewer respondents in the younger age groups
      experienced these difficulties; however, those who did were less likely to be
      receiving help. In most cases, respondents with perceived unmet needs had never
      sought help. In relation to community nursing, this may be associated with the
      lack of knowledge and misconceptions about the roles of community nurses which
      were identified from questionnaire responses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263255
TI  - Research testing theory: a selective review of Orem's self-care theory, 1986
      1991.
AB  - The purpose of this study was to determine the extent to which theory testing may
      have increased in the 5 years since Silva's initial investigation. Using the
      criteria established by Silva, a review of five major research journals in
      nursing was used to investigate the degree to which Orem's self-care theory of
      nursing was being empirically tested. Hand and computer searches yielded 31
      studies purporting to use Orem's theory as the basis for research. Of these
      studies, however, only four (13%) met the criteria for appropriately testing the
      theory. The findings indicate that little change has occurred in using research
      to test Orem's theory appropriately. Implications for research and practice are
      discussed.

PMID- 8263256
TI  - Putting theory into practice: problems and prospects.
AB  - The apparent gap between theory and practice in nursing seems to be widening as
      it is becoming increasingly difficult for nurses to manage multiple theories and
      conflicting knowledge claims for their use in practice. Scientific pluralism in
      nursing provides, on the one hand, a rich array of knowledge about human
      phenomena and ways of dealing with nursing problems, while on the other a set of
      theoretical choices available for knowledge-use in practice. This paper presents
      four ideal-type modes of theory application as viable forms for nurses in
      practice to deal with theoretical pluralism.

PMID- 8263257
TI  - Nurses' knowledge and opinions about the nursing research process in The
      Netherlands.
AB  - Nursing research is just gaining ground in The Netherlands, as it is in every
      European country. Therefore, this study had the purpose of discovering to what
      extent Dutch nurses in the clinical areas have acquired research-based knowledge
      since it was introduced into the country, in the 1970s. Questionnaires, which
      included provision for demographic data, were distributed to 110 nurses,
      comprising head nurses, recently qualified nurses and final-year student nurses.
      A 65% response was achieved and the findings revealed that nursing research as a
      concept was not new to the Dutch nurses. They claimed they had obtained their
      knowledge through nursing training, reading, conferences and other sources such
      as mass media. The head nurses were the most knowledgeable followed by the
      recently qualified nurses and then the student nurses. However, the respondents
      claimed that their knowledge was superficial. The need to extend nurses'
      knowledge through support and encouragement in relation to nursing research
      seminars and conferences is recommended.

PMID- 8263258
TI  - The influence of educational theory on the development of nurse training to
      education in the United Kingdom.
AB  - This paper discusses the development of nurse training to education from its
      historical apprenticeship-style approach to the current position of professional
      education through diploma-level programmes. The influence of education theory on
      nurse training over the years is explored. The slowness of the transition from
      training to education is shown to have been dependent on the view of what is
      considered as appropriate preparation for the role. Historically, one can see
      that it was expedient that preparation for the role began as training, and the
      development to education was thwarted by the lack of resources, the shortage of
      nurses, and the medical and political ideologies of the day. The implementation
      of Project 2000, with students being supernumerary to the workforce, and the
      programme being educationally led, created the need for the development of
      professional education from the traditional training model.

PMID- 8263259
TI  - The discipline of nursing: historical roots, current perspectives, future
      directions.
AB  - As advances in nursing science and research impact upon nursing education and
      clinical practice, new ways of looking at phenomena have led to a re-examination
      and refinement of the traditional concepts: person, environment, health and
      nursing. This evolving pattern of intellectual growth holds promise for the
      discipline of nursing through the advancement of knowledge based upon scientific
      inquiry into the practice of nursing. This paper discusses nursing as a
      discipline by examining the development of a unique body of knowledge from three
      viewpoints: historical past, current perspectives and future direction.

PMID- 8263260
TI  - Nursing science: affiliation with the university.

PMID- 8263261
TI  - Amino acid fortification of protein foods.

PMID- 8263262
TI  - Amino-acids in nutrition and growth. 1914.

PMID- 8263263
TI  - Lysine supplementation of cereal foods: a retrospective.
AB  - During the period 1950-1975, protein and amino acid metabolism and its
      application to world nutrition problems constituted a major focus of nutrition
      research. A large part of this research was concerned with the potential benefits
      to be expected from lysine supplementation of cereal foods, stimulated by the
      availability, beginning in 1955, of commercial quantities of L-lysine
      monohydrochloride from industry. Events during this era and lessons learned are
      reviewed by the author, a participant in the commercialization of lysine.

PMID- 8263264
TI  - Body image and eating behavior in adolescents.
AB  - Approximately two-thirds of adolescent girls at any age are dissatisfied with
      their weight, the proportion increasing with actual weight. Slightly more than
      half of all girls are dissatisfied with the shape of their bodies, an attitude
      which also is positively correlated with body weight. Girls are most likely to be
      distressed about excess size of their thighs, hips, waist and buttocks, and
      inadequate size of their breasts. Those who are dissatisfied with their bodies
      are more likely to engage in potentially harmful weight control behaviors, such
      as dieting, fasting, self-induced vomiting, diuretic use, laxative use and diet
      pill use. Those who diet are more likely to begin in early adolescence, to be
      white than black, to be of higher socioeconomic status, to engage in other eating
      related practices and to have a poor body image and self esteem. Boys who are
      underweight are most likely to be dissatisfied with their weight and many with
      normal weight wish to weigh more. Approximately one-third of boys are
      dissatisfied with their body shape, desiring larger upper arms, chest and
      shoulders. Dieting and purging are less likely than exercise to be chosen by boys
      as methods of weight control. Dieting among boys is more likely to be associated
      with increased body weight and some sports, such as wrestling. Body consciousness
      and altered body image are widespread among adolescents, and may be associated
      with potentially harmful eating practices in both sexes, but more so in girls.

PMID- 8263265
TI  - Thermogenic response to food: intra-individual variability and measurement
      reliability.
AB  - The objective of this study was to assess the reliability and variability of the
      thermogenic response to food (TRF) in healthy adult subjects. Eight healthy
      adults (4 men, 4 women) participated in three sets of measurements of TRF,
      evaluated by indirect calorimetry with a ventilated hood system during 6 hours
      after a standardized meal. The reliability of TRF measurement was estimated using
      a one-way analysis of variance with repeated measurements. After the 6-hour
      period of measurement, the within-subject coefficient of variation for TRF was
      10.7%, while the between-subject variability was twice as high (24.1%, p < 0.01).
      The overall reliability estimate of TRF was acceptable (RE > or = 0.80) after a
      single measurement which lasted at least 6 hours postprandially, while duplicate
      and triplicate measurements reached a similar degree of reliability in 3 hours.
      These results suggest that intra-individual variability contributes little to the
      variability commonly seen in TRF studies, provided that the measurement period is
      at least 6 hours.

PMID- 8263266
TI  - Brief communication: dietary habits of first-year medical students as determined
      by computer software analysis of three-day food records.
AB  - Nutrition training for medical students has long been a low priority for most
      medical schools. Given the growing body of knowledge linking health promotion to
      proper dietary habits, there is a need to increase the quantity and quality of
      nutrition training for medical students. In the present study, first-year medical
      students recorded food intake for 3 days and analyzed their diets for nutrient
      contents with a computer software program. Use of the interactive software
      created a personalized approach to increasing nutrition knowledge as the students
      became aware of their own dietary habits. Female students had a low consumption
      of kilocalories, dietary fiber, calcium, iron, zinc, potassium, and
      polyunsaturated fat. Male students exceeded current recommended intakes for fat,
      saturated fat, cholesterol, and sodium.

PMID- 8263267
TI  - Recent epidemiologic studies on nutrition and cataract in India, Italy and the
      United States.
AB  - Three independent case-control studies with similar methodologies were conducted
      in India, the United States and Italy to investigate risk factors by cataract
      type. Their common objectives were to evaluate risk factors for each cataract
      type, giving priority to nutritional factors, and to determine whether risk
      factors differed among cataract types. Data included self-reporting of food
      frequencies and various biochemical determinations. A higher body mass index was
      the only nutritional factor found by more than one study to be associated with
      cataract, being less frequent in cases than in controls. Blood nutritional status
      from one study showed that a high antioxidant index decreased risk for at least
      one cataract type, high glucose-6-phosphate dehydrogenase values increased risk
      for at least one cataract type, a high albumin globulin ratio decreased risk for
      mixed cataract, and high iron levels decreased risk for cortical cataract. Only
      one of the three studies found that a high nutritional status, high dietary
      antioxidant index, and use of multiple vitamin supplements decreased risk for
      cataract. Findings from these studies suggest socioeconomic and nutritional
      components to cataract risk, although not consistently across studies or cataract
      types. Differences between studies may be due to differences in populations
      and/or data collection methods. Because reducing cataract risk would have major
      implications for a large segment of the population, clinical trials seem
      appropriate to confirm and evaluate the potentially modifiable risk factors
      suggested by these studies.

PMID- 8263268
TI  - Does a vegetarian diet control Wilson's disease?
AB  - The literature indicates that copper (Cu) is less bioavailable from a vegetarian
      as compared to mixed diet. Further, several groups, including ours, find rather
      marginal average Cu intake in the typical American diet. For example, our data
      indicate that Wilson's disease patients on a typical American diet ingest only
      about 25% more Cu than is required. This suggests that a vegetarian diet, if it
      reduced bioavailability by about 25% or more, would be an adequate maintenance
      therapy for Wilson's disease. Observations in two of our patients, who were on
      lactovegetarian diets by choice, and who were almost totally noncompliant with
      anti-Cu therapy, support this view. These observations suggest that vegetarian
      diets may be a management tool for Wilson's disease. They also further emphasize
      the marginal Cu intake in American diets, and suggest that some seemingly healthy
      people, particularly vegetarians, may be at risk for mild Cu deficiency.

PMID- 8263269
TI  - Iron status and iron supplementation in children with classical phenylketonuria.
AB  - Iron (Fe) status and Fe supplementation were assessed in 20 children with
      phenylketonuria (PKU) through dietary intake and through measurements of
      ferritin, hematocrit, hemoglobin, mean cellular hemoglobin, mean cellular volume,
      serum Fe, total iron binding capacity, unbounded iron binding capacity,
      transferrin saturation and transferrin. Findings were compared to reference
      values and to data from age-matched controls. The prescribed phenylalanine
      restricted diet supplied all the recommended nutrients. Dietary Fe was present in
      the diets, but its bioavailability is questionable as several laboratory results
      were not within accepted reference values. A ferrous sulphate supplement (5 mg
      elemental Fe/kg daily) was given for 120 days to a group of PKU children with
      lower Fe parameters, thus changing some of the parameters studied. Serum ferritin
      (p < 0.1), transferrin saturation and serum Fe (p < 0.05) increased after the
      treatment. The need for improved diagnosis of Fe status and determination of
      whether PKU children can benefit from therapeutic Fe is discussed.

PMID- 8263270
TI  - Renal excretion of ascorbic acid: effect of age and sex.
AB  - To determine if the lower plasma ascorbic acid concentrations observed in males
      compared to females, and in the elderly in general, might be due to differences
      in renal clearances of ascorbic acid, tubular maximum reabsorptions (TmAA) and
      renal thresholds for ascorbic acid were determined on older (10 male, 10 female,
      aged 70-86 years) and younger (3 male, 5 female, aged 26-59 years) subjects. The
      mean TmAA for men was 1.54 +/- 0.29 and for women 1.39 +/- 0.33 mg/minute/100 mL
      glomerular filtration rate (p > 0.05). The mean renal threshold for men was 1.51
      +/- 0.25 and for women 1.26 +/- 0.16 mg/dL (p < 0.02). Neither was affected by
      age. If differences in TmAA and renal threshold were to explain the lower plasma
      ascorbic acid concentrations observed in males, both values should have been
      lower than in females. The ability of women to maintain higher plasma ascorbic
      acid concentrations than men, and young higher than elderly, cannot be explained
      by differences in the renal handling of ascorbic acid.

PMID- 8263271
TI  - Blood glucose rise following prenatal vitamins in gestational diabetes.
AB  - Optimal outcome of gestational diabetes mellitus (GDM) is directly related to
      glucose control of the mother. If prenatal vitamins cause a large glycemic
      excursion, then the best prenatal vitamin would be one that produces the lowest
      blood glucose. Nine GDM women participated in two, 8-day test periods. Each
      subject ingested one of six prenatal vitamin-mineral preparations, a placebo, or
      a sucrose capsule, in random order. Blood glucose was determined by the One Touch
      System at 0, 30, and 60 minutes. The sucrose capsule contained 1 g sucrose
      (equivalent to highest glucose/carbohydrate content of any prenatal vitamin). The
      placebo contained 1 g table salt in the same color capsule. Relative glycemic
      index (RGI, defined as the area under glucose curve for the test substance
      divided by the area under glucose curve for 1 g sucrose) and maximum rise of
      blood glucose above time 0 were calculated for each preparation. RGI was
      significantly elevated for all vitamins: TRN 3.86, Natalins Rx 3.00, Filibon
      Forte 2.16, Prenatal Formula 2.10, Materna 1.66, Placebo 1.33, Stuartnatal 1 + 1
      1.16. Two thousand mg vitamin C (n = 4) resulted in an RGI of 1.37. In
      conclusion, ingestion of prenatal vitamins produces a rise in blood glucose
      greater than that seen following ingestion of sucrose equal to the carbohydrate
      content of prenatal vitamins. The cause of the blood glucose rise is not known,
      but it would appear prudent to prescribe a prenatal vitamin with a low RGI.

PMID- 8263272
TI  - Colostrum composition in adolescent mothers.
AB  - Colostrum of high and low (LSEL) socioeconomic level adolescent mothers was
      analyzed to determine the potential influence of adolescence on colostrum's
      chemical composition. Concentrations of total fat, energy, total protein,
      immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G and fatty acids
      were compared to those of adult mothers. The colostrum of adolescent mothers
      showed significantly higher levels of IgA and IgM compared to that of adults.
      Concentrations of lauric, myristic, and palmitic acids were lower in the group of
      LSEL adolescents, when compared to those of adult mothers of the same
      socioeconomic level, probably due to lower lipogenic activity in the former. High
      levels of stearic and oleic acids were found in LSEL adolescents in comparison to
      LSEL adults, despite similar dietary habits. Our results show that breast-feeding
      by adolescent mothers of any socioeconomic level is as indicated as that by adult
      mothers.

PMID- 8263273
TI  - Robert Coles: society's chronicler and conscience.

PMID- 8263275
TI  - Gender differences in attrition from orthopaedic surgery residency.
AB  - We conducted a national survey of orthopaedic surgery residency program directors
      regarding resident attrition. Female residents had a statistically higher
      attrition rate than male residents (p < 0.001). The female early withdrawal
      residents left voluntarily and for personal reasons more often than their male
      counterparts. These tendencies, however, were not statistically significant. We
      feel that more in-depth counseling of female medical students and increased
      mentoring for women in orthopaedic residency could help prevent this attrition.

PMID- 8263274
TI  - The effect of family on the work lives of married physicians: what if the spouse
      is a physician, too?
AB  - Using data from a national survey of pediatricians, this study examines the
      effect of family life on the career choices of 1,782 married pediatricians, one
      quarter of whom were in dual-physician marriages. We hypothesized that marriage
      to physicians would affect the work lives of male pediatricians much as parental
      responsibility does for female pediatricians. Logistic and multiple regression
      models confirmed that marriage to physicians and the presence of children
      affected career decisions of female pediatricians. In addition, male
      pediatricians in dual-physician marriages worked significantly fewer hours than
      other married male pediatricians, although responses to more subjective questions
      indicated that male pediatricians' perceptions of accommodation for the family
      may not match actual adjustments in work effort.

PMID- 8263276
TI  - Maternity leave experiences of resident physicians.

PMID- 8263277
TI  - Maternity leave for housestaff: the experience at one major medical center, 1985
      1992.

PMID- 8263278
TI  - A dream for the future of public health.

PMID- 8263279
TI  - The murders in Rillington Place--a personal recollection.
AB  - The horrifying murders at Rillington Place achieved great notoriety in the 1950s
      for their perpetrator, John Christie. The invesigation that led to Christie's
      conviction for murder involved a large team of experts led by the forensic
      pathologist, Francis Camps. The author recollects the case and describes his
      involvement as an artist in the investigation.

PMID- 8263280
TI  - Infrared photography revisited.
AB  - Applied infrared photography has changed significantly during the last 40 years.
      Its medical application has dwindled while its overall use has increased
      dramatically. An understanding of the electromagnetic spectrum and the
      relationship between what humans are capable of seeing and what infrared
      sensitive film can record will lead to a better appreciation of this film's
      potential application in today's world. Improvements in processing have resulted
      in greater film speed and the direct conversion of the film to positive
      transparencies. This latter development will aid individuals who use the film as
      an educational teaching aid.

PMID- 8263281
TI  - An introduction to fractal imaging technology.
AB  - In this article the author explains the basic theory and practical applications
      of the latest advancement in imaging technology called fractal imaging. Fractal
      imaging is a unique way of compressing and storing images which has unlocked the
      door to the restrictions imposed by conventional imaging technology as regards
      storage and transmission of high quality images. The article outlines how this
      technology has been successfully applied by the creation of the first and only
      fractal photographic archival and retrieval system in Scotland, in the form of
      the George Washington Wilson collection comprising 44,000 images and associated
      text in only 450 megabytes (Mb) of disc space.

PMID- 8263282
TI  - The role of caricature in medicine.
AB  - Syndromes are a combination of several symptoms or characteristics of disease
      which prompt doctors to respond with 'key' treatments and management protocols.
      The essential signs can be abbreviated by the use of caricature. This format may
      prove to be a valuable training tool in clinical observation.

PMID- 8263283
TI  - Photography for litigation--a role for the medical photographer?

PMID- 8263284
TI  - The therapeutic value of medical photography.
AB  - Medical photography is shown to have therapeutic value in illustrating to a
      patient a previously hidden clinical lesion. The sight of the extent and nature
      of a hole in her nasal septum which the patient had caused by picking her nose
      allowed her to stop this habit where previous medication and psychotherapy had
      failed.

PMID- 8263285
TI  - [Occupational activities and pregnancy. Physicians' opinions].
AB  - The aim of this paper is to analyse knowledge, opinions and attitudes of doctors,
      delivering prenatal care, about work and pregnancy. A postal survey was carried
      out in 1989 among all obstetricians and gynecologists and among a random sample
      of general practitioners in two French departments: Val-de-Marne and Aube.
      Response rate was 78% and the sample analysis included 367 respondents. Doctors'
      knowledge about occupational risks for pregnancy, social regulations and their
      attitudes about sick leave certifications are described. They are different
      depending on the specialty--GP or obstetricians--, the geographical department,
      gender and age of the doctors.

PMID- 8263286
TI  - [The ovaries, the immune system, cytokines: physiology].
AB  - Sevellar cellular types are involved together in the cyclical functioning of the
      ovary. Regulating this co-operation between cells are intercellular systems of
      communication both autocrine and paracrine. The immune system that is present in
      the ovary seems to have an important role among the regulatory factors. Cytokines
      are the vectors of intercellular communication. The authors after studying the
      recent literature show how the immune system elements undergo cyclical variations
      corresponding to the ovulatory cycle. Reciprocal co-operation between the
      different cells is brought in to play at all stages of growth and of atrophy of
      the follicle. The knowledge of these networks for regulation make it possible to
      understand what is going on better and to work out a more appropriate treatment
      for certain pathologies such as premature menopause and unforeseen responses to
      certain forms of stimulation of ovulation.

PMID- 8263287
TI  - [The reliability of study methods of the endometrium. A comparative study of 178
      patients].
AB  - OBJECTIVE: To compare the reliability of different methods for investigating the
      endometrium. DESIGN: A prospective study from November 1990 to October 1991.
      SETTING: Department of surgery and gynaecology Diaconesses Hospital, Paris.
      SUBJECTS AND INTERVENTIONS: In a total of 178 symptomatic patients, hysteroscopy
      with curettage in a day-centre under general anesthesia was performed. Before
      this operation, 79 women had had endometrial cytology, 98 women had had
      endometrial biopsy with the endometrial Pipelle, 112 women had ultrasonography
      and 120 women hysterography. MAIN OUTCOME MEASURES: Endometrial cytology and
      biopsy, ultrasonography, hysterography and hysteroscopy were correlated with
      curettage. RESULTS: the Pipelle's diagnostic accuracy appeared better than that
      of cytology. The hysteroscopic diagnosis agreed with the histologic diagnosis
      showed by the curettage except for atypical hyperplasia. The positive predictive
      value for identifying endometrial atrophy with ultrasonography is 100%. A vaginal
      ultrasonographic examination showing an endometrial thickness of < or = 5 mm can
      be used to exclude endometrial carcinoma as the cause of post menopausal
      bleeding. CONCLUSIONS: The combination of hysteroscopy and endometrial biopsy is
      the diagnostic method of choice for the endometrium. It is possible to avoid some
      useless curettages for diagnosis in women with abnormal uterine bleeding.

PMID- 8263288
TI  - [Hysteroscopic metroplasty of uterine septa].
AB  - A series of 23 patients with septate uteri who underwent hysteroscopic division
      of the septum between January 1990 and March 1992 were studied. Before operation
      19 of the 23 patients had 50 pregnancies with 29 spontaneous abortions, 7 late
      abortions, 5 premature deliveries and 9 deliveries at term. Sixteen patients who
      were followed up for more than 6 months conceived 9 times. Six of these went to
      term with 4 normal deliveries and 2 caesarean sections for obstetrical
      indications. There are 2 pregnancies continuing at present (at 25 and 27 weeks of
      amenorrhoea) and one spontaneous abortion in the first trimester. Two patients
      had to be operated on again because a partial residual septum was found post
      operatively.

PMID- 8263289
TI  - [Altitude and pregnancy. Apropos of an experimental study on the pregnant rat].
AB  - Pregnancies that occur at high altitude are bedevilled by many complications and
      particularly those due to pressure disorders. Although there are many maternal
      and placental mechanisms that are brought to bear to "blunt" the effects of
      hypoxia in the fetus, these pregnancies are characterised by low birth weights.
      This work has been carried out to find out the effects of hypoxia during part
      only of the pregnancy. The study was carried out on three groups of ten pregnant
      Wistar Rats: a control group with normal oxygenation (N); a group exposed to
      hypobaric hypoxia during the 4th to the 12th day of pregnancy (480 mmHg,
      equivalent to altitude of 5200 m) (HP); and a group exposed to the same levels of
      hypoxia between the 12th and 20th days of pregnancy (HT). The litters were the
      same size in each group. Mortality of the little rats respectively were 0%, 8.1%
      and 30.6% in groups N, HP and HT (p < 0.001). With hypoxia the rats eat less at
      whichever stage of pregnancy. Weight gain in pregnancy overall was less in the
      groups exposed to hypoxia. The weight gain in the compression chamber was
      particularly low in the early exposed group (HP). The mean weight of the small
      rats was lowered most in group HT (p 0.001). In conclusion, exposure to hypoxia
      is particularly damaging if it occurs in the second half of pregnancy but if
      hypoxia occurs only in the first half of pregnancy there are disturbances.
      Exposure to hypoxia goes up mainly as an increase in neonatal mortality with low
      birth weights.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263290
TI  - [Modeling of feto-placental circulation. Clinical applications apropos of 21
      patients having no or inverse diastolic umbilical flow].
AB  - The placental resistance index: (S-D)/S (S: represents the amplitude of the
      systolic peak and D: the amplitude of the telediastolic peak) is constantly
      inferior to one from the 14th-16th week of amenorrhea during a normal pregnancy.
      The diastolic umbilical arterial blood flow is continuous because of low
      placental vascular resistance. From a clinical study of 21 patients with an
      absent or reversed end diastolic flow in umbilical artery waveforms, an
      obliterative process in the placental vascular tree was observed. A computer
      model was used to stimulate the reversed end diastolic flow in umbilical artery
      waveforms when the placental resistance increased. This haemodynamic approach
      shows that the placental blood flow decreased, and that the arterial blood
      pressure, as well as the pulse wave velocity increased when the placental
      resistance increased. The increase in the difference between the umbilical
      resistance and the placental resistance caused a reduction of the diastolic flow
      owing to a progressive increase of the pulse wave velocity reflected. It was
      concluded that there is a relation between perturbations in placental vascular
      bed and the flow in umbilical artery waveforms.

PMID- 8263291
TI  - [Anencephaly. 10 cases seen in 3 years in Brazzaville (Congo)].
AB  - The authors report ten cases of anencephaly diagnosed between 1989 and 1991 in
      the maternity units of Brazzaville (Congo). The incidence of anencephaly was 0.12
      per thousand. Although there was no geographical factors to definitely identify,
      there is a suspicion that the consumption of potatoes, infected by phytophotora
      infestans at the beginning of pregnancy may have had an effect; but this
      hypothesis would have to be confirmed by microbiological studies. The patients
      were young with a mean age of 27.5 years and were of low socio-economic levels.
      In this study female fetuses were often affected; which is also found in the
      literature but without any reasonable explanation. The means of diagnosis of
      anencephaly in Brazzaville have improved thanks to the recent acquisition of an
      ultrasound machine which made it possible to screen most of these cases.

PMID- 8263292
TI  - [Partial 12q trisomy and chylothorax].
AB  - The authors present a case of partial trisomy 12q associated with chylothorax,
      diagnosed at 30 weeks of pregnancy. Cordocentesis for the karyotype as well as
      thoracocentesis were carried out. In spite of the administration of tocolytic
      drugs the patient delivered a girl with multiple clinical abnormalities, who died
      at 7 days of age. From this case, the authors report 6 other cases of partial
      trisomy 12q in the literature, and, in the discussion they suggest the management
      after the diagnosis of hydrothorax has been made by ultrasound.

PMID- 8263293
TI  - [Hepatitis C and pregnancy: is it necessary to screen for the risk of vertical
      transmission?].
AB  - The diagnosis of the risk for vertical infection with the virus of hepatitis C
      rests on the finding of specific antibodies in the mother. It is rare to see
      clinical signs of infection in the newborn. More frequently asymptomatic
      transmission of the viral genome occurs. As it is important to watch newborn
      infants at risk it is recommended that pregnant women who have a risk factor
      should have serum screening.

PMID- 8263294
TI  - [Essential thrombocythemia and pregnancy. A review of the literature].
AB  - Essential thrombocythemia is a myeloproliferative syndrome confined to platelet
      production. Once the character of a megakaryocyte abnormality has been confirmed,
      the prognosis is good depending on thrombotic and haemorrhagic complications. The
      authors report the outcome of a pregnancy in a patient who had essential
      thrombocythemia treated by anti-aggregating drugs from the 10th week of
      amenorrhoea. In the previous history there were two obstetrical complications of
      the illness (one spontaneous abortion and one intrauterine fetal death). A
      caesarean section carried out after 32 weeks of amenorrhoea led to the birth of a
      baby weighing 1890 gm. Only a few cases have been reported in the literature.
      There is always a drop in the number of platelets in pregnancy. After delivery
      the number of platelets becomes pathological within a few weeks. The prognosis
      for the fetus is linked to the risk of placental thrombosis, not to the numbers
      of platelets. The problem lies in the choice of indications for the use of
      acetylsalicylic acid in low dosage, particularly since cases of pregnancy taken
      to term without any specific type of treatment have been reported.

PMID- 8263295
TI  - [Cancer of the colon and pregnancy: a new case].
AB  - The authors report a first case of cancer of the colon which showed itself by
      parietal inflammation during pregnancy. They point out the difficulty of the
      diagnosis which is not usually found until complications supervene because of the
      mildness of the symptoms and the difficulty in carrying out appropriate tests
      because of the presence of the fetus. The prognosis is very bad and the
      modalities of treatment that can be adopted in the presence of the gravid uterus
      alter depending on the length of gestation. For a patient who has not been
      previously prepared and the discovery is made during an exploratory laparotomy
      the first essential is to perform an ostomy to divert the intestinal contents.

PMID- 8263296
TI  - [Entero-mesenteric venous infarction and pregnancy. A recent case].
AB  - The authors report a case of mesenteric venous infarction in a pregnant woman.
      After having studied the clinical characteristics of this accident, they discuss
      the role of pregnancy in its accuracy and also the therapy that has to be
      adopted.

PMID- 8263297
TI  - [Placenta percreta and uterine rupture. Apropos of 2 cases].
AB  - The authors present two cases of uterine rupture by placenta percreta at 27 and
      36 weeks of gestation. Conservative treatment was used in the first case, and
      radical in the second. Concerning placenta percreta, an overview is presented.
      The pathophysiology is unclear, but a perturbation in the equilibrium between the
      trophoblast and the caduque is accepted. Many factors, maternal uterine and
      placental, contributes to this situation. Clinical presentations are hemorrhage,
      uterine inversion or rupture. The disappearance of the retroplacental anechogenic
      zone is the recent ultrasound's contribution to the early diagnosis. The
      treatment is either radical which is the treatment of choice or conservative and
      the methotrexate could be an interested option.

PMID- 8263298
TI  - [Ogilvie's syndrome after cesarean section. Apropos of 3 cases. Review of the
      literature].
AB  - Ogilvie's syndrome or pseudo-obstruction of the colon shows up as a clinical
      picture of acute obstruction of the large bowel without an associated
      pathological lesion as usually occurs in older patients. Three cases of Ogilvie's
      syndrome following Caesarean section are reported in this work. Caesarean section
      seems to be the most common operative procedure associated with this syndrome. Up
      till now 41 cases have been described in the literature. This syndrome is serious
      because it is possible for the caecum to burst causing faecal peritonitis which
      carries a heavy mortality. Seventeen cases of perforation of the caecum have been
      reported in the literature. The diagnosis is made by x-raying the patient's
      abdomen without any pre-x-ray preparation; if an enema of gastroffin is given it
      can be shown that there is no organic cause for the obstruction. The pathological
      cause seems to be disturbance of the autonomic innervation of the colon. The
      colon should be decompressed rapidly; and the present technique is to do this
      using a colonoscope with or without epidural anaesthesia. Surgery should be
      reserved for cases that have complications or that have been refractory to
      conservative treatment. Of our three cases two were treated successfully by
      colonoscopic decompression and one with the use of drugs.

PMID- 8263299
TI  - [T.O.M. ointment, breast feeding and serum estradiol in newborn infants. A double
      blind, randomized controlled study].
AB  - OBJECTIVE: To study whether there is an iatrogenic transfer of oestradiol through
      the use of T.O.M. ointment administered to prevent or to cure trophic changes in
      the breast while breastfeeding and what the dangers of plasma levels of
      oestradiol in the newborn will be. TYPE OF STUDY: Controlled, randomised, double
      blind. SUBJECTS AND METHODS: 80 mother/infant couples were included in the study:
      40 received the ointment containing oestradiol (the treated group), and 40
      received an ointment without oestradiol (the non-treated group); the ointment was
      applied before each breastfeeding from the 2nd to the 6th or 7th day of life.
      Mothers' milk and blood from the newborn babies were taken for estimating the
      levels of oestradiol using a radio-immunological technique. The total quantity of
      ointment was measured for each subject. RESULTS: The mean level of oestradiol in
      the treated mothers' milk was significantly higher (p. 0.0014) than in the milk
      of the mothers who had not been treated. The concentration of oestradiol in the
      plasma of the newborn dropped from the first to the last day of the trial without
      any difference in the treated or non-treated groups no matter what the sex of the
      child was, nor the quantity of ointment used.

PMID- 8263300
TI  - [Pregnant women performing strenuous work: the application of regulations from
      Social Security].

PMID- 8263301
TI  - Nutritional and environmental risk factors for diarrhoeal diseases in Ecuadorian
      children.
AB  - Risk factors associated with diarrhoea, based on the recall of a recent episode
      were evaluated from a cross-sectional national nutrition and health study in
      1,620 Ecuadorian children less than 5 years old. Prevalence of diarrhoea varied
      with the age of the children; 6- to 23-months-old children showed the highest
      prevalence. In this age range the prevalence of diarrhoea was significantly
      associated with hygienic factors (quality of drinking water, sanitation and
      refuse system), but not with demographic factors (sex, altitude, population
      density, family size). The nutritional status of the children was determined by
      anthropometry and blood chemistry. After stratification for sanitation levels, a
      low weight-for-age Z-score and low serum retinol and zinc concentrations showed a
      statistically significant (p < or = 0.06) association with diarrhoea prevalence
      only in children living under better hygienic conditions. Multivariate analysis
      revealed significant associations between both sanitation levels and nutritional
      level as defined by anthropometry, but not by blood chemistry, and diarrhoea
      prevalence.

PMID- 8263302
TI  - Viral, bacterial and parasitic pathogens associated with severe diarrhoea in the
      city of Sao Paulo, Brazil.
AB  - Viral, bacterial and parasitic pathogens associated with diarrhoea were studied
      in infants and young children admitted to the paediatric clinic of the University
      Hospital of Sao Paulo during the period of 13 months. A recognised pathogenic
      organism was detected in 78% of the diarrhoeic patients, 6% of whom had a mixed
      infection with two agents. Enteropathogenic E. coli (EPEC) was the most common
      enteropathogen detected (22%), followed by rotavirus (19%) and adenovirus (10%).
      Altogether 6% had diarrhoea associated with Salmonella or Shigella and 3% showed
      diarrhoeal illness associated with astrovirus. Infants less than 6 months of age
      were most commonly infected with enterobacteria (35%), mainly enteropathogenic E.
      coli (30%), whereas children 6 months to 2 years presented more often with
      viruses (38%), mainly rotaviruses (25%). Enteropathogens were found during all
      seasons of the year and rotaviruses showed a seasonal variation.

PMID- 8263303
TI  - Evaluation of a probe hybridisation serotyping method for group A rotavirus.
AB  - Serotype-specificity and sensitivity of oligonucleotide probes to serotype human
      rotaviruses was assessed. Probes could detect as little as 6.3 ng of homologous
      RNA and none reacted with as much as 100 ng of heterologous RNA. Northern-blot
      analysis revealed that probes reacted with one of genomic segments 7, 8 or 9 of
      corresponding serotypes.

PMID- 8263304
TI  - Adherence of haemagglutinating and non-haemagglutinating clinical and
      environmental isolates of Aeromonas.
AB  - Twelve haemagglutinating and non-haemagglutinating isolates of Aeromonas spp.,
      comprising 6 each of clinical and environmental origin, were examined for their
      ability to adhere to rabbit intestinal epithelium, for inhibition of adhesion
      with sugars, and for delineation of the portion of intestine, jejunum, or ileum
      that is most susceptible to adhesion. Although the environmental isolates of
      Aeromonas haemagglutinated human erythrocytes that were inhibited by D-mannose
      and/or L-fucose, the majority of the clinical isolates of Aeromonas adhered to
      rabbit intestinal epithelium in almost equal proportions regardless of their
      haemagglutination (HA) properties, species designation, and source of isolation.
      Adhesion of both haemagglutinating and non-haemagglutinating isolates of
      Aeromonas was inhibited by sugars; however, the ability of sugar inhibition to
      adhere was similar to that observed with HA. This study suggests that adhesion is
      probably mediated by a variety of pilus or non-pilus colonisation factors which
      may or may not be a haemagglutinin. The jejunum was found to be more susceptible
      to adhesion than the ileum. However, no appreciable difference was observed in
      the number of adhered bacteria to adjacent loops.

PMID- 8263305
TI  - Home management of childhood diarrhoea in rural Afghanistan: a study in Urgun,
      Paktika Province.
AB  - To gain first-hand knowledge of the incidence of diarrhoea among children less
      than five years old and of the prevailing practices in diarrhoea management, a
      study was carried out in July 1991 in Urgun in Paktika Province of eastern
      Afghanistan. A modified WHO Household Survey Questionnaire was used. Interviews
      with the parents of 338 children revealed that 103 children (30.4%) had diarrhoea
      during the previous 2 weeks. Forty one (39.8%) of these children were given ORS
      obtained from a health worker or bought in the market. The parents of 49 children
      (56.3%) claimed that they also gave an increased amount of fluid, such as plain
      water, soup, yoghurt mixed with water or tea during the diarrhoeal attack.
      Irrespective of receiving ORS therapy, 68 children (66%) were given inappropriate
      medications, including antibiotics, bought from the market. Forty-eight (94.1%)
      of the 51 children who were on exclusive or partial breastfeeding continued to be
      so fed during the diarrhoeal episode. Sixty-five (76.5%) of the 85 children
      accustomed to other additional foods continued to be fed during the diarrhoeal
      attack. Only a few of the parents could define conditions of diarrhoea requiring
      referral.

PMID- 8263306
TI  - A community study on the aetiology of childhood diarrhoea with special reference
      to Campylobacter jejuni in a semiurban slum of Varanasi, India.
AB  - In a community study of 607 diarrhoeal and 529 non-diarrhoeal (control) patients
      less than 5 years old carried out between August 1988 and July 1989, the
      Campylobacter jejuni isolation rate was 4% in the diarrhoeal and 0.9% in the
      control group. It was the second most common bacterial enteropathogen isolated
      after Escherichia coli. Its incidence was more common among 1-2 year old children
      (4.8%) and during rainy season (July-October). Features of dysentery were absent
      in C. jejuni diarrhoea. Findings strongly suggest its aetiological role in
      childhood diarrhoea. Among other enteropathogens in diarrhoeal specimens,
      rotavirus was the commonest (16.4%) followed by enterotoxigenic E. coli (13.8%),
      G. lamblia (10.3%), enteropathogenic E. coli (7.0%), E. histolytica (5.0%),
      Cryptosporidium (3.8%), H. nana spp. (1.5%), NAG vibrios (0.5%), P. shigelloides
      (0.5%), V. mimicus and Salmonella spp. (0.3%). Approximately one quarter of the
      stool specimens (22.6%, 256/1136) tested were positive for the ova of A.
      lumbricoides.

PMID- 8263307
TI  - Prevalence of enteropathogenic and enterotoxigenic Escherichia coli in children
      with and without diarrhoea in Esteli, Nicaragua.
AB  - In Esteli, Las Segovias, Nicaragua, the frequency of isolations of
      enteropathogenic (EPEC), and enterotoxigenic E. coli (ETEC) was investigated in
      100 children with (n = 50) and without diarrhoea (n = 50). EPEC was found to be
      significantly (p < 0.05) more frequent in diarrhoeal (16%) than in healthy
      children (4%). Detailed analyses revealed that 6 serotypes of E. coli were
      involved. Isolation of ETEC was not statistically significantly different (p >
      0.05) in diarrhoeal (28%) and healthy children (16%). Determination of the
      susceptibility of isolated E. coli indicated a high level of resistance to common
      antimicrobial drugs. These resistant strains of E. coli might become a health
      problem in this part of Nicaragua.

PMID- 8263308
TI  - Effectiveness of potash alum in decontaminating household water.
AB  - To evaluate the effectiveness of potash alum in purifying household water, this
      study was carried out in a suburban community in Yangon, Myanmar. It was designed
      to test whether the application of potash alum (0.05%) regularly into household
      water storage vessels during water replenishment was capable of decontaminating
      household water in homes using shallow well water. It was conducted in 100
      households (50 each in intervention and control groups). After alum (0.05%) was
      added, the contamination level of water decreased on the 2nd and 3rd days. The
      alum-treated water was well tolerated by the users; only one member complained of
      a metallic taste. We conclude that potash alum was effective and acceptable in
      this community in decontaminating household water.

PMID- 8263309
TI  - Bibliography on diarrhoeal diseases.

PMID- 8263310
TI  - The effects of d- and l-fenfluramine (and their interactions with d-amphetamine)
      on cortisol secretion.
AB  - Twelve normal weight healthy male volunteers participated in a double-blind,
      placebo-controlled trial of the effects of d- and l-fenfluramine, d-amphetamine,
      and the interactions between the two isomers of fenfluramine with amphetamine, on
      cortisol secretion. d-Fenfluramine and d-amphetamine in combination produced the
      greatest cortisolaemic effect, suggesting that they act by differing
      neurochemical pathways. d-Fenfluramine produced a significant effect, but l
      fenfluramine produced little effect, suggesting that the cortisol-releasing
      properties of racemic fenfluramine reside in the d-isomer.

PMID- 8263311
TI  - Fluoxetine versus amitriptyline in the treatment of major depression: a
      multicenter trial.
AB  - Fluoxetine, a serotonin uptake inhibitor, and amitriptyline, a tricyclic
      antidepressant, were compared in a 5-week, multicenter, double-blind, randomized
      trial in 136 out-patient men and women, aged 21-70 years, with major depressive
      disorder. Overall efficacy was comparable with fluoxetine and amitriptyline
      [Hamilton 21-Item Rating Scale for Depression (HAM-D21), Raskin, Covi, Clinical
      Global Impressions-Severity and -Improvement, Patient's Global Impressions]. Mean
      +/- standard deviation decreases in HAM-D21 total score were 12.9 +/- 9.9 and
      11.6 +/- 10.3 (p = 0.423), respectively. Response rates (> or = 50% decrease in
      HAM-D21 total score) for patients treated > or = 4 weeks were 46.7% and 66.0% (p
      = 0.039) and remission rates (HAM-D21 total score < or = 7) were 18.3% and 28.3%
      (p = 0.209), respectively. Response and remission rates for all patients were
      comparable with fluoxetine and amitriptyline. Study completions were higher with
      fluoxetine than amitriptyline (87.7% vs 66.2%; p = 0.003). Discontinuations for
      adverse events were higher with amitriptyline than fluoxetine (22.5% vs 6.2%; p =
      0.007). More treatment-emergent nausea and insomnia were reported with fluoxetine
      (p < or = 0.05); more anticholinergic and orthostatic events and weight gain were
      reported with amitriptyline (p < or = 0.05). Statistically, but not clinically,
      significant changes were observed in vital signs. Both fluoxetine and
      amitriptyline were effective treatments for out-patients with major depressive
      disorder. Fluoxetine had a more favorable safety profile than amitriptyline.

PMID- 8263312
TI  - Tardive dyskinesia, lipid peroxidation, and sustained amelioration with vitamin E
      treatment.
AB  - Plasma levels of thiobarbituric acid reactive substances (TBARS) were measured as
      an indicator of lipid peroxidation, in 14 patients suffering from tardive
      dyskinesia (TD). There was a highly significant positive correlation between
      plasma TBARS (both basal and iron stimulated) and severity of TD. Patients were
      then treated for 1 month with the free radical scavenger vitamin E (1200 i.u.
      daily). Following vitamin E treatment, there was a clinically and statistically
      significant amelioration of TD, and this improvement was maintained at follow-up
      7-13 months later. There was no consistent or significant change in plasma TBARS
      levels related to treatment with vitamin E.

PMID- 8263313
TI  - Acute effects of the novel antidepressant venlafaxine on cognitive event-related
      potentials (P300), eye blink rate and mood in young healthy subjects.
AB  - Venlafaxine is a novel non-tricyclic antidepressant, which preclinically has
      demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects.
      In this study acute effects of single oral doses of placebo, 12.5 mg, 25 mg, and
      50 mg venlafaxine on event-related potentials (ERPs), eye blink rate and mood
      were studied in 16 healthy subjects. ERPs were investigated in an auditory odd
      ball paradigm before as well as 3 h after each drug intake. In addition to 17 EEG
      leads, vertical and horizontal EOGs were recorded. After EOG minimization and
      visual artefact rejection the peak latencies of the spatial average were
      determined by an automatic procedure. The applied methods of data acquisition,
      artefact processing, objective component determination and statistical analysis
      were successful in describing acute effects of venlafaxine on ERPs in normals. N1
      and P2 latencies were not affected. An increase in P2 amplitude in the relevant
      central and frontal regions was seen, reflecting some effect on automatic
      information processing. Stimulus evaluation time was not affected, as P300
      latency remained unchanged. P300 amplitude was not affected at the relevant
      central and parietal region. Blink rate was not changed. By means of the
      adjective checklist a dose-dependent decrease of "extroversion" and "high
      spirits" and an increase of "introversion" was observed. Our findings suggest
      that venlafaxine affects human information processing less than would be expected
      from the more centrally inhibiting classical antidepressants.

PMID- 8263314
TI  - An open study of oral flesinoxan, a 5-HT1A receptor agonist, in treatment
      resistant depression.
AB  - Flesinoxan, a full 5-HT1A receptor agonist, was administered (4-8 mg) to
      treatment-resistant depressed patients in an open study. Safety and tolerance of
      the substance appeared satisfactory. Headache, dizziness and nausea were the most
      frequently reported side effects. The observations suggested that flesinoxan is
      an antidepressant agent and that it may be of particular value in some difficult,
      treatment-resistant depressions. Based on these observations, a double-blind,
      placebo-controlled evaluation of flesinoxan's efficacy appears warranted.

PMID- 8263315
TI  - A study on serum prolactin levels in schizophrenia: correlation with positive and
      negative symptoms.
AB  - Serum prolactin levels are determined in 116 schizophrenics and 120 control
      subjects. Values of prolactin levels of the patients are compared with the values
      of control of the same sex and age group. There is no significant difference
      between prolactin levels of controls and those with negative or positive symptoms
      of schizophrenia. Analysis, taking age into account, also does not show any
      significant difference between patients with positive or negative symptoms and
      controls. The relationship between nature of symptoms of schizophrenia and serum
      prolactin levels varies in different studies. The possible reasons for such
      variations are discussed.

PMID- 8263316
TI  - A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the
      prevention of relapse of major depression.
AB  - A total of 147 patients who had responded in a placebo-controlled study to 6
      weeks treatment of an episode of DSM-III-R major depression with either 20 mg or
      40 mg citalopram were randomized double-blind to continue on the same dose of
      citalopram or to receive placebo during a 24-week study of the efficacy of
      citalopram in the prevention of relapse. The citalopram 20 and 40 mg groups
      showed a significant advantage compared with placebo both in relapses (p < 0.05)
      and in the survival analysis of time to relapse (p = 0.01 and p = 0.02,
      respectively). Both 20 and 40 mg citalopram appeared similarly safe and well
      tolerated with little difference in side effects from placebo. The results
      demonstrate that citalopram, at a dose of both 20 and 40 mg is effective and well
      tolerated in continuation treatment to consolidate response. The relapse rate in
      patients who had responded to placebo during the 6-week acute treatment study,
      who were continued double-blind with placebo but not included in the efficacy
      analysis, was similar to the rate in the formal placebo control group, suggesting
      that patients who respond to placebo in a short treatment course may nonetheless
      require long-term active treatment to prevent relapse.

PMID- 8263317
TI  - Paroxetine is better than placebo in relapse prevention and the prophylaxis of
      recurrent depression.
AB  - In an investigation of the efficacy of paroxetine in relapse prevention and
      prophylaxis of depression, patients who met DSM-III-R criteria for major
      depression with a history of two or more previous episodes in the preceding four
      years and who had responded to eight weeks treatment with paroxetine, were
      randomized double-blind to receive either paroxetine 20-30 mg or placebo for one
      year. One hundred and seventy-two patients entered open treatment of whom 141
      completed eight weeks treatment. One hundred and thirty-five responders entered
      the double-blind placebo-controlled study. There was a significant advantage for
      paroxetine compared with placebo in the reappearance of depression (p < 0.01) and
      in the time to reappearance (p < 0.001) over the one-year study. A significant
      advantage was seen for paroxetine compared with placebo in the first four months
      in relapse prevention (p < 0.01) and in the time to relapse (p < 0.005), and in
      the later period of treatment in preventing recurrence in the time to recurrence
      (p < 0.05). Paroxetine was effective in preventing the reappearance of depression
      following an acute illness. These results confirm the benefit of long-term
      pharmacotherapy for treating depressive illness.

PMID- 8263318
TI  - Double-blind study of the efficacy and safety of sertraline versus fluoxetine in
      major depression.
AB  - An eight-week double-blind, multicentre study was performed to evaluate the
      efficacy and safety of sertraline vs. fluoxetine in the treatment of major
      depression (DSM-III-R). There were 108 out-patients, from nine Italian centres,
      entered into the study, of whom 88 were evaluable (48 sertraline, 40 fluoxetine).
      The final mean daily dose of sertraline was 72 mg and for fluoxetine it was 28
      mg. Both treatment groups showed a statistically significant improvement from
      baseline at one week, and this was maintained until the end of treatment for all
      of the following measures: Hamilton Rating Scales for Depression and Anxiety, the
      Montgomery Asberg Depression Rating Scale, Clinical Global Impressions Scale,
      Zung Self-Rating Scale for Anxiety and the Leeds Sleep Evaluation Questionnaire.
      Although there was a numerical advantage for sertraline on several efficacy
      measures, there was no statistically significant difference found between the
      treatment groups. The incidence of adverse events was similar for both
      treatments; 40.4% for sertraline and 39.3% for fluoxetine. However, adverse
      events were generally rated by patients as of lower severity in the sertraline
      group. In addition, for the fluoxetine group, there was a higher incidence of
      agitation, anxiety and insomnia than for sertraline. Sertraline was considered to
      be better tolerated than fluoxetine overall, since only 9.6% of sertraline
      treated patients discontinued treatment due to therapy failure whereas in the
      fluoxetine-treated group this figure was 19.6%. By contrast, 13.5% of sertraline
      treated patients discontinued prematurely because of clinical improvement,
      compared with 10.7% of fluoxetine-treated patients.

PMID- 8263319
TI  - Does mianserin induce involuntary movements in brain damaged patients?
AB  - A case of involuntary movements reappearing during mianserin treatment after 33
      years of absence in a 69-year-old woman is described. A noradrenergic alpha-2
      receptor-mediated mechanism is suggested.

PMID- 8263320
TI  - Can severe cardiorespiratory dysregulation induced by clozapine monotherapy be
      predicted?
AB  - Severe orthostatic and cardiorespiratory dysregulation may occur during
      institution of clozapine therapy both during concomitant benzodiazepine
      medication and on reinstitution of clozapine after a washout period. Extensive
      medical and neurological workup before and after the trials can nevertheless be
      normal. The absence of similar previous reactions to other drugs, adhering to
      monotherapy with clozapine, increasing dosage slowly or performing a single test
      for orthostatic reactions after initiating clozapine are insufficient
      precautionary measures. Cardiorespiratory complications can occur without the
      challenge of assuming an erect position but appear to otherwise run an initial
      course similar to that of severe orthostatic reactions. A significantly abnormal
      response to testing for orthostatic reactions may be established, but only during
      the period of vulnerability to cardiorespiratory dysregulation. Repeated testing
      for this predisposition during the first weeks of clozapine therapy is suggested.

PMID- 8263321
TI  - Histochemical detection of binding sites for human growth hormone using
      biotinylated ligand.
AB  - Recombinant human growth hormone was covalently linked to biotin via a six-carbon
      spacer arm. Biotinylation was confirmed by electrophoresis and mass spectrometry
      showed that approximately 50% of the hormone was monobiotinylated. The modified
      growth hormone (GH) was shown to bind to the GH receptor of IM9 human lymphoid
      cells with an affinity of 0.55 x 10(9) M-1. Bioactivity of biotinylated GH
      measured in the Nb2 bioassay was 53.9% that of unlabeled GH. GH binding sites on
      human IM9 cells were visualized histochemically with the biotinylated hormone, a
      technique that provides a means of identifying receptors for GH on target cells
      in vitro.

PMID- 8263322
TI  - Adaptation of the reverse hemolytic plaque assay to electron microscopy: a study
      of the individual secretory activity in prolactin cell subpopulations.
AB  - We used the reverse hemolytic plaque assay (RHPA), a method for detecting
      secretion by single cells, to demonstrate functional heterogeneity among
      prolactin (PRL) cells of rat anterior pituitary at the light microscopic (LM)
      level. We attempted to adapt RHPA for electron microscopy (EM) to define the
      relationships between fine structure and secretory activity in individual PRL
      cells. A major modification of the technique, intended to improve preservation of
      ultrastructure, was allowing the cells to recover after their enzymatic
      dispersion from the pituitary tissue, through a brief (3-4 hr) culture step
      before the assay. Adaptation for EM was achieved by the use of plastic slides for
      construction of specialized Cunningham chambers, permitting application of all
      the EM procedures (flat embedding, punching of selected areas) usually employed
      for cultured pituitary monolayers. Moreover, immunocytochemical pre- and post
      embedding methods were also applied for cell identification and study of
      subcellular hormone distribution. Such a modified RHPA enabled us to analyze the
      ultrastructure of plaque-forming cells surrounded by their companion red blood
      cell ghosts. The first results with EM RHPA showed that under basal conditions a
      subpopulation of PRL cells containing small granules (150-200 nm) was actively
      secreting, whereas PRL cells with large (300-600 nm) and irregular granules
      appeared to be stimulated by thyrotropin-releasing hormone or KCl. The EM RHPA
      technique described here might receive more general application and could be
      utilized for study of many other secretory systems.

PMID- 8263323
TI  - Ultrastructural visualization and neurochemical characterization of spinal
      projections of primary sensory afferents from the nipple: combined use of
      transganglionic transport of HRP-WGA and glutamate immunocytochemistry.
AB  - We used transganglionic transport of the neuronal tracer horseradish peroxidase
      coupled to wheat germ agglutinin (HRP-WGA) and post-embedding immunogold staining
      to determine the spinal projections and neurochemical identity of sensory
      afferents originating from a discrete cutaneous area. After SC injection of
      tracer into the nipple of lactating rats and reaction with tetramethylbenzidine
      stabilized with diaminobenzidene (TMB-DAB) or DAB and cobalt (TMB-DAB-Co), we
      found labeled terminals in the internal part of the first two layers of the
      dorsal horn where they formed axodendritic synapses and, at times, central
      elements of glomeruli, synaptic complexes believed to be involved in the
      integration of sensory messages. Immunogold staining of ultra-thin sections of
      tissue reacted with TMB-DAB-Co revealed that many mammary afferents contained
      glutamate as putative neurotransmitter. This combined approach thus offers the
      possibility of marking a limited set of primary afferents, after capture of
      tracer by sensory receptors of restricted peripheral areas, to visualize their
      projections at the spinal level and to determine their neurochemical nature with
      electron microscopy.

PMID- 8263324
TI  - Immunocytochemical localization of androgen receptor with polyclonal antibody in
      paraffin-embedded human tissues.

PMID- 8263325
TI  - Expression of IL-6 mRNA in normal rat and human pituitaries and in human
      pituitary adenomas.
AB  - Cells expressing IL-6 mRNA were detected by in situ hybridization in normal
      pituitaries. In normal untreated rat pituitary the expression was very low.
      Within hours after IP administration of liposaccharide, IL-6 mRNA accumulated in
      the anterior lobe of the pituitary. Production of IL-6 was monitored after
      dissociation and culture of pituitary cells. High levels (8000 pg/ml) were
      recovered after 72 hr in culture. In normal human pituitaries, less than 1% of
      cells expressed IL-6 mRNA or IL-6 receptor mRNA (IL-6-R mRNA). In
      gonadotropinomas, prolactinomas, and non-functioning adenomas, only rare,
      scattered positive cells were found for either IL-6 or IL-6-R. In contrast, both
      genes were highly expressed in ACTH- and GH-secreting tumors at the junction of
      adenoma and infiltrating fibrous tissue and around blood vessels. The combined
      expression of IL-6 and IL-6-R suggests that IL-6 acts in an autocrine or in a
      paracrine way in ACTH and GH adenomas.

PMID- 8263326
TI  - Expression of myosin heavy chain isoforms in developing human muscle spindles.
AB  - We studied serial sections of human fetal limb muscles (10-25 weeks of gestation)
      by light microscopic (LM) immunocytochemistry, using specific antibodies against
      slow-tonic, slow-twitch, fetal, embryonic, and alpha-cardiac myosin heavy chain
      (MHC) isoforms, neurofilament protein, laminin, and myomesin. One set of the
      first-generation myotubes expressed slow-tonic MHCs, and slow-twitch, fetal, and
      embryonic MHCs from the tenth week of gestation. These primary myotubes were
      identified as developing nuclear bag fibers. Second-generation myotubes in close
      apposition to the primary nuclear bag myotubes initially expressed only fetal and
      embryonic MHCs. One or more of these secondary myotubes acquired expression of
      slow-tonic and slow-twitch MHCs and gave rise to nuclear bag fibers. Most of the
      nuclear bag precursors expressed alpha-cardiac MHC. The secondary myotubes that
      expressed fetal and embryonic MHC but not slow-tonic, slow-twitch, or alpha
      cardiac MHCs gave rise to the nuclear chain fibers. This study shows that
      different populations of fiber precursors, each with a unique sequence of MHC
      expression, gave rise to the nuclear bag and chain fibers, despite the presence
      of a common afferent nerve, from the early stages.

PMID- 8263328
TI  - Medical profession and Consumer Protection Act.

PMID- 8263327
TI  - Monoclonal antibodies against the protein core and glycosaminoglycan side chain
      of glomerular basement membrane heparan sulfate proteoglycan: characterization
      and immunohistological application in human tissues.
AB  - We raised monoclonal antibodies (MAb) against the core protein and the heparan
      sulfate (HS) side chain of heparan sulfate proteoglycan (HSPG) from glomerular
      basement membranes (GBM). Anti-HSPG-core MAb were obtained after immunization of
      mice with HSPG purified from human GBM and the anti-HS MAb after immunization of
      mice with HSPG from rat glomeruli, which crossreacted with human HS and GBM HSPG.
      The specificity of the MAb was demonstrated by ELISA studies, Western blotting,
      inhibition experiments, and indirect immunofluorescence (IF) on kidney cryostat
      sections pre-treated with glycosaminoglycan (GAG)-degrading enzymes. Indirect IF
      on normal human kidney tissue showed prominent GBM staining for both MAb, with
      variable staining of the other renal basement membranes (BMs). By indirect
      immunoelectron microscopy (IEM), most intense staining was observed at the
      endothelial side of the GBM for both MAb, although the staining patterns were not
      identical. Both MAb were used to localize HSPG in human tissues by indirect IF.
      They bound to antigens present in the BMs of most tissues examined, including
      those of epithelia and endothelia. Differences between both MAb were observed for
      BMs of muscle cells, since the anti-HSPG core protein MAb (JM-72) staining was
      negative, whereas the anti-HS MAb (JM-403) clearly stained these structures.
      Comparison of our staining patterns in human tissues with the distribution of
      other anti-BM HSPG antibodies suggests that there are at least two types of BM
      HSPG, which have common epitopes on the HS side chains recognized by JM-403.

PMID- 8263329
TI  - Future of family planning practitioners.

PMID- 8263330
TI  - Testicular biopsy in cases of male infertility: a retrospective study.
AB  - One hundred testicular biopsies performed during the period of 1983-90 were
      reviewed to reappraise the value and utility of testicular biopsy in cases of
      male infertility. All the biopsies were categorised into the following 7 types
      and their relative incidences were determined. There were 16% normal cases.
      Hypospermatogenesis was found in 42% cases, maturation arrest in 18% cases,
      Sertoli cell-only syndrome in 17% cases, Klinefelter's syndrome in 3% cases,
      orchitis in 3% cases and tubular sclerosis in 1% case. Testicular biopsy findings
      were correlated with semen analysis reports. Azoospermia was represented by all
      the above 7 types whereas oligospermia was represented hypospermatogenesis and
      maturation arrest varieties. Testicular biopsy is most useful in azoospermia but
      its value is limited in oligospermia.

PMID- 8263331
TI  - Role of intraperitoneal drains on subhepatic collection following routine
      uncomplicated cholecystectomy.
AB  - The effect of intraperitoneal drains on the incidence and significance of
      subhepatic fluid collection following elective cholecystectomy was prospectively
      evaluated by ultrasound scanning in 200 patients. Subhepatic area was drained in
      100 patients by using corrugated and vacuum drains while no drains were used in
      100 patients. Subhepatic collection was detected in 12 patients (12%) in the
      drainage group and only 4 patients (4%) in the non-drainage group. The difference
      is statistically significant (p < 0.05). Two patients (2%) in the drainage group
      required re-exploration. Overall morbidity (30%) was higher in the drainage group
      than non-drainage group (18%). It is concluded that routine use of drains
      following elective cholecystectomy should be abandoned and they should be used
      only when indicated.

PMID- 8263332
TI  - Leukaemoid reaction in diarrhoeal diseases.
AB  - There was an outbreak of diarrhoea/dysentery in Naxalbari, North Bengal in August
      September of 1992. Ninety-seven cases were investigated. Bacterial pathogens were
      isolated from stools of 17 cases and the organisms were Salmonella typhimurium
      (76%), Salmonella enteritidis (12%) and Shigella dysenteriae type 1(12%). A
      leukaemoid reaction was observed in 4 cases (24%) amongst all 17 patients and
      they were all children.

PMID- 8263333
TI  - Ethylene glycol poisoning treated by haemodialysis.

PMID- 8263334
TI  - Plasmacytoma of maxilla.

PMID- 8263335
TI  - Inflammatory malignant fibrous histiocytoma.

PMID- 8263336
TI  - Irreducible tubo-ovarian inguinal hernia.

PMID- 8263337
TI  - Accidents in childhood in and around home.

PMID- 8263338
TI  - How should medical malpractice claims be handled? An economist's view.

PMID- 8263339
TI  - Applicability of the Consumer Protection Act to the medical profession.

PMID- 8263340
TI  - Consumer protection not for doctors forum!!!

PMID- 8263341
TI  - The Consumer Protection Act and the doctors.

PMID- 8263342
TI  - Can the Consumer Protection Act, 1986 encompass medical service?

PMID- 8263343
TI  - Hypervitaminoses.

PMID- 8263344
TI  - Infertility and gamete intrafallopian transfer.

PMID- 8263345
TI  - Justification of the composition of WHO formula ORS.

PMID- 8263346
TI  - Solid tumours of the ovary.
AB  - One hundred seventeen solid ovarian tumours, diagnosed histologically during the
      period between 1971 and 1990, were studied. The overall incidence of solid
      ovarian tumours was 23.4% of all the ovarian tumours (500 cases) studied. Of 117
      solid ovarian tumours 19 (16.2%) were benign and the rest 98 (83.8%) were
      malignant. Epithelial tumours were the commonest (28.2%) followed by germ cell
      tumours (22.2%), sex cord stromal tumours (21.4%), metastatic tumours (19.7%) and
      non-specific tumours (8.5%). The average age (26.8 years) was comparatively low
      for germ cell tumours otherwise in other groups it ranged between 42 and 45
      years. Below 15 years immature teratoma was diagnosed in 4 cases and granulosa
      cell tumour in 2 cases. Bilateral tumours were seen in 22 cases (23.2%) out of 95
      cases observed. Pain and fullness in the pelvic region were observed in 94.9%
      cases. Varied morphological picture was seen in 6 cases of endometrioid
      carcinoma. Dysgerminoma constituted 6.8% of solid ovarian tumours. Gliomatosis
      peritonei was noticed in one case of immature teratoma. Granulosa cell tumour
      accounted for 11.1% of solid ovarian tumours. Of 23 cases of metastatic tumours,
      Krukenberg tumour was noticed in 88.9% cases. Diagnostic problems as well as
      prognostic factors of solid ovarian tumours have been discussed.

PMID- 8263347
TI  - Ultrasound guided percutaneous renal biopsy.
AB  - Percutaneous renal biopsy is a useful tool in the diagnosis and prognostication
      of the medical renal diseases. The ultrasonography helps in accurately localising
      the site of renal biopsy as well as in detecting contra-indications like
      polycystic disease, solitary kidney and hydronephrosis, etc. In this series of
      100 consecutive cases of ultrasound guided renal biopsy, the success rate was 99%
      and reasonably good length of renal tissues were obtained in 97% cases.

PMID- 8263348
TI  - Fine needle aspiration cytology in the evaluation of lymphoreticular tumours of
      mediastinum.
AB  - The role of needle aspiration cytology in the diagnosis of 52 cases of
      lymphoreticular tumours of mediastinum was evaluated from January 1985 till May
      1992. Cytological analysis showed 41 cases of non-Hodgkin lymphoma, 9 cases of
      Hodgkin's disease and 2 cases of benign lymphoid hyperplasia. The cytological
      interpretations were compared to histopathological diagnosis. In the present
      series, a definite diagnosis of lymphoma was possible in all the cases but exact
      subclassification was correctly possible in 89.6% cases. There was no false
      positive report or any complication.

PMID- 8263349
TI  - Cerebral palsy.
AB  - In a prospective study it was found that cerebral palsy constituted 0.29% of
      total paediatric outdoor cases during the study period of 1988-1990. Seventy-five
      children suffering from cerebral palsy were studied at SN Children Hospital,
      Allahabad. Male to female ratio was 1:2. There were 42.8% cases who belonged to
      the age between one and 2 years. Hypertonic cases were predominant over hypotonic
      cases (3:1). Hemiplegia was commonest (68%) while triplegia was least common
      (2.7%). There were 24.5% cases who were mentally retarded. Hypertonic cases
      improved more frequently than hypotonic cases. An early management by paediatric
      physiotherapy may play an important role in the treatment of cerebral palsy.

PMID- 8263350
TI  - A 5-year study of caesarean hysterectomy cases.
AB  - There were 53 cases where caesarean hysterectomy was done during the last 5 years
      at Eden Hospital, Calcutta. Majority of the cases were in the age group of 22-32
      years and parity varied from 0 to 6. There were 54.71% cases which were due to
      rupture of previous caesarean section scar mostly lower uterine segment done in
      teaching institutions. Seventy per cent cases were booked. Only 8 babies survived
      following caesarean hysterectomy. Maternal mortality was nil. By good intranatal
      monitoring, more vigilance, performing less caesarean section and better health
      education one can lower the incidence of caesarean hysterectomy.

PMID- 8263351
TI  - The health properties of lactic bacterial preparations.

PMID- 8263352
TI  - Dementia: the devastating global problem of twenty-first century.

PMID- 8263353
TI  - [Molecular mechanism for immunoglobulin class switching and multiple isotype
      expression].

PMID- 8263354
TI  - [Recent progress in the studies of phosphatidylinositol 3-kinase].

PMID- 8263355
TI  - [Signal transduction by c-Kit].

PMID- 8263356
TI  - [Microtubule-associated proteins].

PMID- 8263357
TI  - A model mechanism for the chemotactic response of endothelial cells to tumour
      angiogenesis factor.
AB  - In order to accomplish the transition from avascular to vascular growth, solid
      tumours secrete a diffusible substance known as tumour angiogenesis factor (TAF)
      into the surrounding tissue. Endothelial cells which form the lining of
      neighbouring blood vessels respond to this chemotactic stimulus in a well-ordered
      sequence of events consisting, at minimum, of a degradation of their basement
      membrane, migration, and proliferation. A model mechanism is presented which
      includes the diffusion of the TAF into the surrounding host tissue and the
      response of the endothelial cells to the chemotactic stimulus. The model accounts
      for the main observed events associated with the endothelial cells during the
      process of angiogenesis (i.e. cell migration and proliferation); the numerical
      results compare very well with experimental observations. The situation where the
      tumour (i.e. the source of TAF) is removed and the vessels recede is also
      considered.

PMID- 8263358
TI  - Diffusion approximations for stochastic compartmental models.
AB  - A diffusion approximation is developed for one-compartment systems with nonlinear
      elimination rates. Both impulsive input and continuous infusion are considered.
      Explicit expressions for the mean and autocovariance functions of the contents of
      the compartment as time elapses are given.

PMID- 8263359
TI  - Effects of vaccination programmes on transmission rates of infections and related
      threshold conditions for control.
AB  - This study addresses the problem of the existence of conditions for persistence
      or eradication of age-dependent directly transmitted infections. The usual system
      of differential equations describing the dynamics of the disease is transformed
      into integral equations. The authors show how to solve these equations and, by
      applying the contraction mapping theorem, give conditions for the persistence or
      eradication of the infection. A practical illustration of the application of the
      methods proposed is sketched, using data for rubella collected from a small
      Brazilian community.

PMID- 8263360
TI  - Thresholds and stability analysis of models for the spatial spread of a fatal
      disease.
AB  - A simple two-class (susceptibles and infectives) model describing the dynamics of
      a fatal disease in a variable-size population is presented and analysed. Spatial
      dependence is introduced into the model by considering two different mechanisms
      for the geographic spread of the disease: nonlocal interaction between
      susceptibles and infectives, and migratory spread of the animals. The steady
      states and their stability for these spatially dependent models are deduced; no
      spatially heterogeneous steady states were possible. For nonlocal interaction,
      there were two spatially uniform steady states: the trivial state (no infectives
      or susceptibles), which was unstable, and the endemic state (constant proportion
      of the population infected), which was locally asymptotically stable. With
      migratory spread, the number of spatially uniform steady states was dependent on
      the boundary conditions imposed. With hostile (Dirichlet) boundary conditions,
      only the trivial steady state was possible and its local stability found to
      depend on the rate of diffusion of the total population. With no-flux (Neumann)
      boundary conditions, the steady states are the trivial and endemic states; these
      were unstable and locally asymptotically stable, respectively.

PMID- 8263361
TI  - MR imaging of musculoskeletal sarcomas: the clinical significance of peritumoral
      low signal intensity lines in planning surgical margins.
AB  - The authors studied 33 musculoskeletal sarcomas, comparing preoperative MRIs with
      postoperative pathological evaluations based on JOA criteria. Fifty-one sites
      were investigated to determine the clinical significance of a low signal
      intensity line (LSL) on the outer margin of the tumor image. LSLs at different
      sites were counted as individual cases, since they sometimes showed different
      characteristics at different sites. An LSL showing a consistent width and no
      change on either of two time-weighted images (T1-W or T2-W) was evaluated as a
      strong LSL, and was thought to represent a barrier preventing tumor penetration.
      In cases showing a strong LSL, resection beyond the line can provide a safety
      margin, even if defind as a marginal procedure according to the JOA criteria. In
      cases showing only a faint LSL, a high rate of tumor cell presence was observed
      external to the line; in such cases the surgical plan must be focused on the
      attainment of a curative margin.

PMID- 8263362
TI  - [Design of cementless femoral prostheses adaptive to secondary osteoarthritis of
      the hip joint].
AB  - In order to design cementless femoral prostheses for the femoral canal of
      Japanese patients with secondary osteoarthritis of the hip joint, we analyzed the
      anatomical features of the hip joint in 85 hips of 55 patients with
      osteoarthritic hip and 90 hips of 60 subjects with normal hip in three
      dimensional CT images. We found that 9 different stem designs varying in width
      and proximal radius were required to accommodate the hips with secondary
      osteoarthritis. In normal hips, the anatomical features of the proximal femoral
      canal to the femoral length was directly proportional. Thus, the values for the
      proximal radius, the position of the isthmus, off-set value and width of the stem
      for femoral neck fracture and aseptic necrosis of the femoral head should
      increase with the stem size, but the ratios of the increase were found different.
      The mean taper angle from the lower end to the lesser trochanter to the upper end
      of the isthmus was 3.8 degrees regardless of femoral length.

PMID- 8263363
TI  - [Reconstruction for brachial injury by the accessory nerve--anatomy of the
      accessory nerve and its innervation of the trapezius--Japan].
AB  - At present reconstruction of not only elbow function, but also wrist and fingers
      function is possible for totally paralysed root avulsion type of brachial plexus
      injuries by means of multiple nerve transfers and free muscle transplantation.
      Although denervation of the trapezius muscle may be a problem, the accessory
      nerve is used as the donor nerve for reconstruction. Forty-seven cadaver
      dissections were performed to determine the innervation of the trapezius. In 98%
      of the regions, branches of the accessory nerve or the cervical nerves were found
      to be directly innervated with the accessory nerve in the posterior triangle of
      the neck without anastomosis. This study came to the conclusion that it was
      possible to use the accessory nerve as the donor nerve without paralysis of the
      upper part of the trapezius, if the accessory nerve was used at an adequate
      point. Since the course of the accessory nerve is similar to one of the cervical
      nerve in the posterior triangle of the neck, it is difficult to distinguish them.
      The layer of the course and the great auricular nerve at the posterior margin of
      the sternocleidomastoid are reference points of the accessory nerve and the
      cervical nerves.

PMID- 8263364
TI  - [A double-blind dose ranging study of weekly subcutaneous administration of
      rHuEPO (KRN5702) on post-phlebotomy anemia of patients scheduled for predeposit
      autologous blood transfusion (multicenter late PhII study)].
AB  - Preoperative blood reservation for autologous blood transfusion generally causes
      anemia. We performed a double blind controlled study to determine the optimal
      dose of subcutaneous rHuEPO (recombinant human erythropoietin, KRN5702) for
      preventing preoperative anemia due to blood reservation. Patients received
      KRN5702 subcutaneously once a week in a doses of 12000, 24000 or 36000 IU by a
      double blind technique. After storage of 1200 ml of their own blood right before
      surgery, their hemoglobin (Hb) averaged about 1 and was about 0.5 g/dl lower than
      the level before administration of KRN5702 in doses of 12000 and 24000 IU,
      respectively. This fall was significant. In patients receiving KRN5702 in a dose
      of 36000 IU, the level of Hb rose instead of a fall; Hb immediately before
      surgery was 1.1% higher than that before administration which, however, was not
      significant. This elevation indicates a possibility of abnormal elevation of Hb
      at this dose. The mean Hb value right before surgery was significantly lower in
      patients receiving 12000 IU KRN5702 than in patients of the other two groups. The
      recovery rate of Hb was an indicator to reflect improvement of anemic conditions,
      and increased as the dose increased after the blood reservation. The rate in the
      12000 IU group was significantly lower than that in the other two groups; there
      was not much difference between the other two rates. We estimated that to reserve
      1200 ml of autologous blood, 24000 IU of KRN5702 is adequate but not excessive.
      One patient receiving 24000 IU showed side effects including an elevation of body
      temperature, rash, and edema.

PMID- 8263365
TI  - The mechanism of bradykinin-induced arachidonic acid release in osteoblast-like
      MC3T3-E1 cells phospholipase A2 activation by bradykinin and its regulation by
      protein kinase C and calcium.
AB  - In the present study, we investigated the mechanism by which bradykinin (BK)
      enhances [3H]arachidonic acid release in murine osteoblast-like MC3T3-E1 cells
      prelabeled with [3H]arachidonic acid. BK enhanced [3H]arachidonic acid release in
      a time- and concentration-dependent manner, when cells were stimulated in the
      presence, but not in the absence, of extracellular Ca2+. It appears that the BK
      induced [3H]arachidonic acid release was attributed to the activation of
      phospholipase A2, since a phospholipase A2 inhibitor, mepacrine, significantly
      inhibited the BK enhancement of [3H]arachidonic acid release whereas a
      diacylglycerol lipase inhibitor, RHC80267, failed to do so. Furthermore, it was
      found that a protein kinase C inhibitor, staurosporine, and down-regulation of
      protein kinase C by prolonged exposure of cells to phorbol 12-myristate 13
      acetate inhibited the BK-induced [3H]arachidonic acid release. These results
      provide evidence that BK stimulation of MC3T3-E1 cells activates phospholipase A2
      to liberate arachidonic acid by the mechanism which involves both Ca2+ and
      protein kinase C.

PMID- 8263366
TI  - [Effect of endurance running training on the structural and metabolic properties
      of partially denervated soleus muscle in rats].
AB  - To estimate the influence of partial denervation on the skeletal muscle, a
      histochemical and biochemical study was performed on the soleus muscle. Partial
      denervation was carried out by cutting the proximal root of the nerve innervating
      the soleus muscle. Further, the effect of endurance running training on the
      recovery of the partially denervated muscle was examined. Partial denervation did
      not cause apparent diminution of the number of muscle fibers, nor the muscle
      weight. Four weeks after denervation, histological changes such as grouping
      atrophy, fiber splittings, and invasive phagocytes were observed in the
      denervated portion of the muscle. In the non-running group, mean cross-sectional
      fiber area of each muscle fiber type increased significantly at 4 weeks after
      denervation. On the other hand, mean cross sectional fiber area of type II fibers
      increased at 8 weeks after denervation in the running group. The oxidative enzyme
      activities were significantly increased in the partially denervated muscle by
      endurance running training after 4 weeks of denervation. The results indicate
      that the influence of partial denervation gradually extends over the whole
      muscle. Furthermore, the running exercise appears to add a good effect to a
      recovery of the function and the maintenance of muscle structures.

PMID- 8263367
TI  - [Cell mediated calcification in three-dimensional collagen gel culture of the
      osteoblast-like cells derived from rat calvaria].
AB  - Osteoblast-like cells were obtained by sequential enzymatic digestion of 19-day
      fetal rat calvaria and cultured within native type 1 collagen gels in alpha-MEM
      supplemented with 10% fetal bovine serum and 10 mM beta-glycerophosphate for 3
      weeks. Cells were also cultured as monolayers in the usual manner and used as
      controls. The collagen gel discs contracted by one tenth in diameter after 4
      days. The cells in the collagen gels seemed to proliferate at a low rate and to
      differentiate immediately into round cells, spindle-like cells, and adipocytes.
      In the monolayer cultures, calcifications were recognized after 2 weeks only in
      the high-density confluent areas where cells were disposed in multiple layers and
      alkaline phosphatase activity was high. In the collagen gels, some cells showed
      high alkaline phosphatase activity after 1 day of culture and calcifications were
      observed after 1 week around the cells with intense alkaline phosphatase
      activity. In collagen gel cultures, the degree of alkaline phosphatase activity
      and of calcification correlated with the density of the cell suspension at the
      time of seeding. The round cells were thought to be osteoblasts since they showed
      high alkaline phosphatase activity and were closely related to initial
      calcifications. Some of the spindle-like cells also showed high alkaline
      phosphatase activity and were apparently involved in the calcification process in
      the latter phase of culture, so that some of them seemed to be resting
      osteoblasts or lining cells. In electron-microscopical studies, initial
      calcification was related to the so-called matrix vesicles, and hydroxyapatite
      crystals were detected in mitochondria. Gap junctions which are specific to
      osteocytes were observed mainly between the round cells, but also between the
      round cells and the other cells. This culture system in which cells form a three
      dimensional network is suitable to investigate osteoblastic functions and cell
      mediated calcification in vitro.

PMID- 8263368
TI  - ECG of the month. Alternate route. Ventricular preexcitation pattern.

PMID- 8263370
TI  - Resource allocation.

PMID- 8263369
TI  - Carcinoma of the oral tongue.
AB  - Carcinoma of the oral tongue is the second most common malignancy of the oral
      cavity. Major risk factors include tobacco and alcohol usage. Early diagnosis is
      the cornerstone of successful management. Comprehensive evaluation and treatment
      modalities are reviewed. For early lesions, surgery or radiation therapy may be
      employed with equal efficacy. For advanced lesions, combination radiotherapy and
      surgery are advocated. Chemotherapy is still experimental, but continues to
      undergo multicenter investigations for treatment of oral tongue carcinoma.

PMID- 8263371
TI  - Making the most of your family tree.

PMID- 8263372
TI  - Entering private practice: the jump from residency to the real world.

PMID- 8263373
TI  - The evolving role of thoracoscopy in the diagnosis and treatment of chest
      disease.
AB  - Between April 1, 1988 and April 1, 1993, 88 patients underwent thoracoscopic
      procedures for diagnosis or treatment or both of diseases which had previously
      been approached by standard thoracotomy in our practice. Fifty-three (60.2%) were
      men and 35 (39.8%) women. The median age was 63, range 19 to 88 years. Although
      the indications for operation generally fell into one of five categories, the
      ultimate diagnoses established by the procedure spanned a wide array of chest
      pathology. Morbidity and mortality remained low and length of stay in hospital
      was favorable in comparison with a subset of patients with malignant pleural
      disease who underwent thoracotomy for diagnosis. Thoracoscopy, or video-assisted
      thoracic surgery (VATS), is a procedure which compares favorably with traditional
      thoracotomy in selected patients and its horizons as a diagnostic and therapeutic
      tool continue to expand.

PMID- 8263374
TI  - Nutrition Screening Initiative and the Louisiana Food for Seniors experience.
AB  - The Nutrition Screening Initiative (NSI), an interdisciplinary agency, has
      developed three levels of nutritional screening for the elderly. Nutritionists
      from the Office of Public Health and the Orleans Parish Nutrition Commodity
      Service screened 104 Commodity Supplemental Food Program--Food for Seniors (CSFP)
      participants utilizing the NSI's checklist. Anthropometric measures were also
      obtained and the Body Mass Index (BMI), a measure of total body fat, was
      calculated. Eighty percent of the participants were at moderate or high
      nutritional risk. Fifty percent of the obese participants (BMI > 30) were at high
      nutritional risk; whereas 83% of underweight participants (BMI < 21) were at high
      nutritional risk. Results suggest the need for further evaluation and nutritional
      intervention among low-income seniors.

PMID- 8263375
TI  - ECG of the month. Fingerprints or smudges? Narrow-QRS tachycardia.

PMID- 8263376
TI  - Congenital and genetic sensorineural hearing loss.
AB  - One in 750 neonates will have a sensorineural hearing loss of which approximately
      40% will be due to a genetic defect. The causes of congenital and genetic
      sensorineural hearing loss are abundant, and their associations with other
      diseases are quite diverse. The early detection of hearing loss is of the utmost
      importance because it can affect development even within the first year of life.
      A familiarity with the numerous causes of sensorineural hearing loss and their
      associated abnormalities allows for early detection. Rehabilitation of the
      hearing loss as well as treatment of the associated organic defects and
      assistance through genetic counseling is often indicated.

PMID- 8263377
TI  - Thrombotic thrombocytopenic purpura.

PMID- 8263378
TI  - Guidelines for conduct of managed care. The LSMS Committee on Insurance.

PMID- 8263379
TI  - A self-image profile analysis of spina bifida adolescents in Louisiana.
AB  - With the growing number of spina bifida children reaching adolescence and
      adulthood and the national thrust toward "mainstreaming" disabled children, there
      is increasing need for research on the problems of social and psychological
      adaptation. The goal of this study was to obtain a normed, psychosocial self
      image profile of Louisiana's adolescent spina bifida population. Offer's self
      image scale was administered to a sample of 50 Louisiana spina bifida
      adolescents, ranging from 11 to 21 years of age. The sample's self-image profile
      was statistically compared to a normal profile, as a group, by age, by gender,
      and by level of vertebral disability. With the exception of the sexuality
      dimension, which was significantly below normal, especially in females, 10 of the
      11 dimensions were statistically within normal limits. Correlations of self-image
      subscales with gender, age, and disability revealed several curious and
      potentially important findings.

PMID- 8263380
TI  - CO2 laser stapedotomy.
AB  - Operative approaches to correct stapedial otosclerosis continue to be refined. In
      the last decade the use of the laser in stapedotomy has become increasingly
      common. The decision to use visible (Argon, KPT-532) versus invisible (CO2)
      lasers continues to be debated. CO2 laser light has ideal optical properties in
      micro-otologic surgery, but because of delivery problems its use was difficult.
      Recent advances in laser technology have facilitated the use of the CO2 laser.
      Eighty-four patients in the past 3 years have undergone small fenestra laser
      stapedotomy. Results are available on 82. Of these, 91% had closure of the air
      bone gap within 10 db. Complications and morbidity were minimal. CO2 laser
      stapedotomy is a safe procedure with low morbidity in the correction of hearing
      loss caused by stapedial otosclerosis.

PMID- 8263382
TI  - Cochlear interdependence and micromechanics in man and their relations with the
      activity of the medial olivocochlear efferent system (MOES).
AB  - Following stimulation of one ear with white noise (WN) or 0.5, 1 and 2 kHz tone
      bursts a statistically valid mean reduction in the amplitude of delayed evoked
      otoacoustic emissions (DEOE), elicited from the contralateral ear by bursts of
      the same frequencies, was observed in 10 people (19-23-years-old) with normal
      hearing. This reduction only appeared in response to a contralateral stimulus
      delivered 7, 8 and 9 ms earlier than that used to produce the DEOE. This
      inhibitory effect was just referable to the activity of the medial olivocochlear
      efferent system (MOES). This research has shown that: (i) the cochlear
      interdependence is linked to activation of the MOES; (ii) in man the activity of
      MOES is inhibitory and only appears for a stimulus of the same frequency or (for
      WN) including that used to elicit DEOE; (iii) the cochlear interdependence is
      frequency selective and the MOES thus establishes a direct functional
      interdependence between homologous sectors of the organs of Corti on the two
      sides; (iv) DEOE would appear to be no more than partly generated by outer hair
      cells (OHC) of the organ of Corti in relation to the frequency of the stimulus
      employed, thus substantiating the hypothesis that in their production the effects
      of an 'active' mechanism, represented by the 'slow' contractile activity of the
      OHC, is overlain by those of a 'passive' mechanism formed by the oscillations
      induced by the movements of the stapes in the basilar membrane (BM) or in the set
      of membranes and liquids of cochlear canal.

PMID- 8263381
TI  - Otorhinolaryngological diseases in the Minoan era.
AB  - Minoan civilization was one of the civilizations of the past and flourished in
      the island of Crete between the years 2600 B.C. and 1100 B.C. Archaeological
      excavations brought to the light buildings and items, showing that the Minoans
      had an extensive knowledge about hygiene and health matters. Among the items were
      idols, depicting anatomical parts of the human body and different pathological
      changes. These idols were offered by suffering people to gods and goddesses in
      order to beg for their help in curing them. In a study carried out on idols kept
      in the Heraklion Museum, a number of interesting anatomical details and
      pathological changes, concerning the head and neck area were recognized.

PMID- 8263383
TI  - Xenograft versus autograft in tympanoplasty.
AB  - This retrospective study compares the tympanoplasty success rate when using a
      xenograft (Zenoderm) or an autograft (temporalis fascia). Fifty-three ears were
      operated on over a three-year period. All the tympanoplasty operations were
      performed by the same surgeon. There were 43 ears in the temporalis fascia
      autograft group and 10 ears in the Zenoderm xenograft group. Both groups were
      similar with respect to patient age, type of tympanoplasty, area of tympanic
      membrane perforation and condition of the contralateral ear. The tympanoplasty
      success rate in the temporalis fascia autograft group was 95 per cent. The
      tympanoplasty success rate in the Zenoderm xenograft group was only 40 per cent.
      All Zenoderm tympanoplasty failures were regrafted with temporalis fascia
      autograft. There was a 100 per cent success rate with this salvage surgery. In
      conclusion, we suggest that Zenoderm is not a suitable graft material for
      tympanoplasty.

PMID- 8263384
TI  - The prognostic value of mucociliary clearance in predicting success in
      tympanoplasty.
AB  - Mucociliary and equipressive eustachian tube functions have been studied, using
      saccharin solution (five per cent sodium saccharinate) and tubal manometry
      respectively, in 58 ears with chronic disease undergoing tympanoplasty. The
      position of the perforation site determines the results as the poorest results
      are obtained from the posterior ones, positive cases (47 per cent) and mean
      transport time (37.7 minutes), compared to the greater percentage of positive
      cases (86 per cent) and mean transport time (22.2 minutes) for anterior
      perforations. When both parameters are analysed together there is a direct
      relationship between normal equipressive function and normal mucociliary
      transport time and between negative transport time and tubal blocking.
      Significant difference in transport times have been found for the anterior and
      posterior perforations being shorter for the anterior ones. When surgical outcome
      is correlated with mucociliary transport, the normal transport time percentage is
      seen to be considerably higher in the success group (50 per cent) than in the
      failure group (22 per cent).

PMID- 8263385
TI  - What causes acute otitis externa?
AB  - External otitis is an extremely common condition and can affect between five to
      twenty per cent of the patients attending ENT clinics (Hawke et al., 1984). Its
      precise pathogenesis remains unclear, despite several aetiological
      classifications in the literature. The aim of this study was to investigate the
      relationship between infection, water exposure and trauma and the development of
      acute otitis externa. The study comprised 100 patients with their first attack of
      otitis externa and 150 age and sex matched controls. In only 40 per cent of cases
      could a primary microbiological cause be found. There was no significant
      statistical difference found between the two groups regarding the use of agents
      capable of traumatizing the external canal. Regular swimming, showering and hair
      washing were significantly more common in patients with acute otitis externa.
      Allergic disorders were nearly three times more common in the external otitis
      group suggesting a possible immunological aetiology.

PMID- 8263386
TI  - Nasal packing after routine nasal surgery--is it justified?
AB  - Ninety-five patients undergoing routine nasal surgery were enrolled into a
      randomized, prospective trial to investigate the efficacy and morbidity of nasal
      packing. The patients were randomized to receive a bismuth iodoform paraffin
      paste (BIPP) pack, a Telfa pack or no pack. Patients for septal surgery were
      randomized between the BIPP and Telfa groups only. They were independently
      randomized to receive or not receive, a silastic nasal splint for the first post
      operative week. Post-operative pain levels were analysed using a visual analogue
      scale. Mean pain scores were increased 50 per cent by the use of nasal packs and
      pack removal, particularly BIPP which, was a most painful event (p < 0.001).
      Reactionary haemorrhage occurred in only two patients (2.1 per cent), both of
      whom had packs in situ. Vestibulitis was unique to the patients with a silastic
      splint, who were packed with BIPP, occurring in 21 per cent of them. Similarly
      septal perforation was unique to this group. There was no significant difference
      in the incidence of adhesions between the groups which received packs and those
      who did not. Routine nasal packing, especially with BIPP, would seen difficult to
      justify in view of the increased pain levels and increased complications which
      occur without any demonstrable benefit in the majority of patients. Therefore
      packing should be reserved for cases where there is concern about persistent
      haemorrhage. In these cases Telfa would be preferable to BIPP.

PMID- 8263387
TI  - Inferior turbinate resection: the need for a nasal pack.
AB  - A random prospective study of 180 patients with chronic nasal obstruction who
      underwent inferior turbinate resection as a part of a multinasal surgical
      procedure is presented. The aim of our study was to examine the influence of
      nasal pack on the incidence of post-operative haemorrhage following inferior
      turbinate resection. The haemorrhage rate in Group 1 (no nasal pack), Group 2
      (nasal pack retained for 24 hours) and Group 3 (nasal pack retained for 48 hours)
      was 11.7, 8.3 and 0 per cent respectively. We recommend that a nasal pack should
      be retained for 48 hours following inferior turbinate resection.

PMID- 8263388
TI  - An in vitro comparison of the Erbium: YAG laser and the carbon dioxide laser in
      laryngeal surgery.
AB  - This study compares the relative thermal damage caused by a surgical CO2 laser
      and the Erbium:YAG laser when used to incise the human vocal fold in vitro.
      Results show that charring is completely eliminated when using the Erbium:YAG
      laser. The depth of coagulative necrosis adjacent to an incision is reduced from
      510 microns (+/- 75) using the CO2 laser to 23 microns (+/- 12) using the
      Ebrium:YAG laser and at the base is reduced from 125 microns (+/- 45) using the
      CO2 laser to 12 microns (+/- 8) using the Erbium:YAG laser. The potential
      advantages regarding post-operative healing after laryngeal surgery are
      discussed.

PMID- 8263389
TI  - A comparison of radiotherapy and surgery as primary treatment in the management
      of T3 N0 M0 glottic tumours.
AB  - Seventy-four patients with Stage T3 N0 M0 squamous carcinoma of the glottis were
      treated initially by either surgery or radiotherapy between 1980 and 1985. The
      treatment adopted was determined by consultant preference. The long-term survival
      in both groups was approximately the same. Of 38 patients treated initially by
      radiotherapy, 25 had local recurrence. Fifteen of these underwent salvage surgery
      and 10 died of disease. Thirteen patients (33 per cent) retained their larynx.
      One of the major advantages of treating patients with stage T3 N0 M0 carcinoma of
      larynx by radiotherapy initially is that approximately one-third will retain
      their larynx. Local recurrences can usually be treated readily by salvage
      surgery.

PMID- 8263390
TI  - CGRP-immunoreactive cells supplying laryngeal sensory nerve fibres in the cat's
      nodose ganglion.
AB  - Through a combination of retrograde staining by wheat germ agglutinin (WGA) and
      immunohistochemistry, calcitonin gene-related peptide (CGRP)-reactive sensory
      neurons projecting from the laryngeal mucosa were detected in the feline nodose
      ganglion. The size of the CGRP-immunoreactive cell which was regarded as a
      laryngeal sensory neuron, was about 60 microns in diameter: the shape of the
      immunoreactive laryngeal sensory neuron was unipolar. CGRP-reacted laryngeal
      sensory cells were found in the rostral part of the nodose ganglion extending to
      the middle part. They aggregated in the most rostral part, were sparse in other
      parts and were approximately 50 per cent of WGA-reactive laryngeal sensory
      neurons in number. Our results suggest that this neurotransmitter might play an
      important role in laryngeal peripheral sensory innervation.

PMID- 8263391
TI  - External laryngeal trauma: analysis of thirty cases.
AB  - A retrospective analysis of thirty patients with external laryngeal trauma was
      performed to assess the type and extent of injuries commonly seen as well as the
      outcome following treatment. Outcome was assessed both in terms of voice and
      airway. Major laryngeal injuries (19 cases) outnumbered minor injuries (11
      cases). A good correlation exists between the symptoms of haemoptysis and stridor
      at presentation and severity of the injury (p = 0.002). Early surgical
      intervention is associated with better outcome (p = 0.01). However there is no
      statistically significant difference in outcome between major and minor injuries
      (p = 0.3) indicating that other factors are operative in determining outcome.
      Based on our findings a management strategy for patients with external laryngeal
      trauma is outlined.

PMID- 8263392
TI  - Predictive factors of a complete response to and adverse effects of a CDDP-5FU
      combination as primary therapy for head and neck squamous carcinomas.
AB  - Retrospective analysis of detailed patient and tumour factors associated with a
      complete response to combination inductive chemotherapy with CDDP-5FU (96 or 120
      hour continuous infusion) was performed using data from 147 patients with a
      previously untreated squamous cell carcinoma of the oral cavity, oropharynx or
      pharyngo-larynx following completion of two (29 patients) or three (118 patients)
      cycles. Adverse reactions to chemotherapy were documented for all 164 patients
      included in the study. Eight drug-related deaths occurred due to: acute
      myocardial infarction (five patients), peptic ulcer disease (two patients) and
      severe neutropenia with sepsis (one patient). Severe non-lethal complications
      included marrow depletion (14 patients), peptic ulcer (two patients),
      thrombophlebitis (seven patients), angina pectoris (two patients), stroke (one
      patient), pulmonary oedema (one patient) and convulsions (one patient). Six
      patients refused further treatment because of untoward side effects and tumoral
      progression was observed in three cases. Separate response rates for the primary
      site and nodes were determined and analysis of respective predictive factors of
      response was performed. Complete response was obtained in 31 per cent at the
      primary site versus 18 per cent for the nodes (p < 0.05). The combined (primary
      site + nodes) overall complete response rate was 22 per cent. Among 11 factors
      studied (age, sex, performance status, primary site, tumour differentiation,
      initial resectability, 5FU dosage per cycle, number of cycles, T, N and TN
      stages), only performance status, N stage, resectability and number of cycles
      were associated with a combined complete response. Multivariate analysis showed
      performance status, N stage, TN stage and resectability to be significant
      predictive factors of a combined complete response.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263393
TI  - Recurrent meningitis due to a congenital fistula of the stapedial footplate.
AB  - A rare case of a congenital fistula of the stapes footplate, in a 10-year-old
      girl, resulting in recurrent meningitis, is reported. A full ENT examination and
      a high index of suspicion, is essential if the diagnosis is to be made.
      Exploratory tympanotomy should be considered on clinical grounds, even if a high
      resolution CT scan of the temporal bones does not show any anomalies, in order to
      ascertain the definite diagnosis of a fistula and to seal it permanently.

PMID- 8263394
TI  - Sensorineural hearing loss caused by metastatic prostatic carcinoma: a case
      report.
AB  - Metastases to the temporal bone are a recognized, if rare, cause of otological
      symptoms including sudden sensorineural hearing loss. Carcinoma of the prostate
      is a common cancer which frequently metastasizes to bone but is only rarely
      reported in the temporal bone. We report a case of sudden sensorineural hearing
      loss due to metastatic prostatic carcinoma in the temporal bone.

PMID- 8263395
TI  - Osteoma of the external auditory meatus presenting as an aural polyp.
AB  - Isolated osteomata of the external auditory canal are benign and often
      symptomless lesions, and are distinct from the much commoner exostoses. A case is
      reported in which an osteoma presented as a recurrent 'aural polyp' due to a
      fibroepithelial polypoid reaction in the overlying skin. The polyp and the
      osteoma were excised surgically. We believe this to be the first reported case to
      present in this manner.

PMID- 8263396
TI  - Primary cerebral lymphoma presenting with bilateral cerebellopontine angle
      lesions.
AB  - A case is described of a primary cerebral lymphoma which presented with bilateral
      cerebellopontine angle lesions. No similar case has been reported in the English
      language in the last 25 years. The literature is reviewed and discussed.

PMID- 8263397
TI  - Granular cell tumour of the larynx in an eight-year-old girl.
AB  - Granular cell tumour is a rare benign neoplasm, that can affect many parts of the
      body, as single or multiple lesions. It is more common in black people and
      females. Typically it occurs between the fourth and fifth decades of life, with
      the median age for the laryngeal variety as 36 years. About 30 to 50 per cent
      occur in the tongue and 30 per cent in the skin. A case of granular cell tumour
      of the larynx is reported in an eight-year-old girl, presenting with hoarseness
      of voice. She was successfully treated with local excision of the tumour. This
      tumour is rare in the larynx where it is more common in males than females
      although granular cell tumours are found more frequently in females generally.
      For these reasons the authors suspect that their case, of a laryngeal granular
      cell tumour occurring in an eight-year-old girl might be the youngest to be
      reported.

PMID- 8263398
TI  - Extranotochordal chordoma presenting as multiple neck masses: report of a case.
AB  - Chordomas are rare tumours which arise from notochordal remnants. A primary
      cervical chordoma of extranotochordal origin, sparing osseous structures, was
      excised by a bilateral neck dissection. The patient was disease-free two and a
      half years later.

PMID- 8263399
TI  - Implantation metastasis following percutaneous endoscopic gastrostomy.
AB  - Since it was first described, the original percutaneous endoscopic gastrostomy
      (PEG) technique has proved to be a valuable adjunct in patients with head and
      neck tumours. This procedure is being increasingly utilized in the face of
      swallowing impairment related to head and neck carcinoma. Although generally well
      tolerated, it may be associated with complications. In this report, we document
      tumour implantation at the percutaneous endoscopic gastric site and review the
      report cases. It appears that implantation metastasis does alter prognosis.

PMID- 8263400
TI  - Cervical thymic cyst--a case record.
AB  - Cystic lesions of the thymus are rare. In a large series of over 200 mediastinal
      cysts only 12 cases of thymic cysts have been reported (Seltzer et al., 1968).
      Cervical thymic cysts are so rare that only 35 cases have been documented in the
      English literature.

PMID- 8263401
TI  - Submaxillary hypoglossal neurilemmoma.
AB  - Neurilemmomas of the hypoglossal nerve are uncommon neoplasms. A unique case of
      submaxillary hypoglossal neurilemmoma is presented with radiological and surgical
      results. Methods of diagnosis and differential diagnosis are discussed.

PMID- 8263402
TI  - Carotid sinus syndrome in parapharyngeal tumours.
AB  - We describe three cases of metastatic carcinoma in the parapharyngeal space
      associated with the Carotid Sinus Syndrome. This has not been previously
      described.

PMID- 8263403
TI  - Metastatic Hurthle cell tumour causing central airway obstruction.
AB  - A Hurthle cell tumour is a variant of follicular thyroid cell carcinoma. This is
      a report of metastatic Hurthle cell tumour causing central airway obstruction,
      emphasizing the difficulty in differentiating benign from malignant lesions.

PMID- 8263404
TI  - Adult T-cell leukaemia-lymphoma in Waldeyer's ring: a report of three cases.
AB  - Adult T-cell leukaemia-lymphoma (ATLL) is a new type of T-cell malignancy which
      has an adult onset, a rapidly progressive terminal course and a clustering at
      patients' birthplaces in southeast Japan and the Caribbean. We report the
      clinical features of three cases of ATLL in Waldeyer's ring, which has been
      rarely reported in the literature. The patients complained of throat pain and
      lump in the neck. They received combination chemotherapy, but all died within a
      year of first noticing the symptoms.

PMID- 8263405
TI  - Facial palsy after glomus tumour embolization.
AB  - A case is presented of a patient undergoing pre-operative embolization of a
      glomus tumour who developed a facial palsy one hour after embolization. At the
      time of surgery it was found to be due to the embolization material (polyvinyl
      alcohol foam) blocking the stylomastoid artery. The blood supply of glomus
      tumours and the variations in the blood supply of the facial nerve are discussed.

PMID- 8263406
TI  - Hyoid bone tumour mass presenting with cervical nodal metastasis.
AB  - This paper presents a quite unique case report of a patient presenting with the
      combination of cervical metastatic lymphadenopathy and a hyoid bone tumour mass.
      The differential diagnosis and treatment is discussed, with emphasis on the
      importance of immunohistochemistry and electron microscopy in the management of
      such a case.

PMID- 8263407
TI  - Cannabis in the ear--the legal aspects.

PMID- 8263408
TI  - Selective composition of biliary phosphatidylcholines is affected by secretion
      rate but not by bile acid hydrophobicity.
AB  - Little is known about the mechanisms of: 1) biliary phosphatidylcholine (PC)
      secretion by the hepatocyte, 2) selectivity for biliary 1-palmitoyl-2-linoleoyl
      PC (PLPC) secretion, and 3) exclusion of 1-stearoyl-2-arachidonyl-PC (SAPC) from
      bile. The experiments were designed to determine, in rats, whether selectivity
      (for PLPC and against SAPC) is influenced by bile acid hydrophobicity or
      secretion rate. We examined the effects of bile acid depletion and of ileal
      infusion of taurocholic acid, tauroursodeoxycholic acid, and
      taurochenodeoxycholic acid. Compared to bile acid depletion, infusion of each
      bile acid caused PLPC to decrease from 59% of bile PC to 48%, and SAPC to
      increase from 2.6% to 5%. Bile acid hydrophobicity had no effect on PC
      selectivity, but selectivity decreased to a moderate degree as total PC secretion
      increased. To determine whether selectivity is for preformed molecular species,
      we used a new method to isotopically label four species of hepatic PC. This was
      done by intravenous injection of PLPC and SAPC labeled in the linoleate (14C) and
      arachidonate (3H) moieties. Assuming rapid mixing of each PC species in the
      hepatocyte as supported by the specific activity data, bile SAPC and SLPC were
      derived entirely from hepatic preformed SAPC and SLPC; bile PLPC was from both
      preformed PLPC (55%) and an unlabeled input (45%, probably direct secretion of
      newly synthesized PLPC). In conclusion, the selective composition of bile PC is
      not related to bile acid hydrophobicity, but is partially lost as secretion
      increases within the physiologic range.

PMID- 8263409
TI  - Absorption and distribution of arachidonate in rats receiving lysophospholipids
      by oral route.
AB  - Absorption and distribution of polyunsaturated fatty acids was investigated in
      rats receiving lysophospholipids per os (30 mg kg-1). Lysophosphatidylcholine
      (lysoPC) increased [3H]arachidonate absorption and its incorporation into mucosal
      phosphatidylcholine. Transport of [3H]arachidonate by the phospholipid fraction
      of lymph lipoproteins and the level of [3H]arachidonate in plasma and liver
      lipids was also increased by lyso PC. Lysophosphatidylserine also increased
      [3H]arachidonate absorption but channeled the fatty acids into the
      aminophospholipid fraction of mucosal phospholipids, thus decreasing its efflux
      in lymph lipoproteins. As a consequence, lysophosphatidylserine caused
      [3H]arachidonate accumulation in mucosa. As similar results were obtained with
      [14C]linoleate, the data suggest that the addition of an appropriate
      lysophospholipid to the diet may direct absorption and distribution of
      polyunsaturated fatty acids.

PMID- 8263410
TI  - Specificity of lipoprotein lipase binding to endothelial cells.
AB  - Lipoprotein lipase (LPL) hydrolyzes circulating lipoprotein triglyceride
      molecules while it is associated with the luminal surface of capillary
      endothelial cells. The precise molecular mechanism by which LPL attaches to these
      cells is unknown. LPL and a number of other molecules, including growth factors
      and clotting factors, bind to heparin-affinity gels and are eluted using high
      concentrations of salt. Of these molecules, antithrombin III and basic fibroblast
      growth factor have been shown to bind to specific cell surface heparan sulfate
      proteoglycans. Recent data from our laboratory (Sivaram et al. 1992. J. Biol.
      Chem. 267: 16517-16522) have shown that a heparin-sensitive, non-proteoglycan 116
      kDa LPL-binding protein is present on cultured bovine aortic endothelial cells
      (BAEC). A series of experiments was performed to study the specificity of LPL
      binding to BAEC and to this 116-kDa protein. At low amounts of LPL (1 microgram)
      125I-labeled LPL binding to the cells was inhibited up to 82% by the addition of
      a 20-fold excess of unlabeled LPL. LPL binding to the BAEC was not decreased by
      the addition of similar amounts of either antithrombin or thrombin. Specific LPL
      binding was eliminated by incubating the BAEC at 4 degrees C with heparin
      containing buffer prior to the addition of LPL. Although cellular internalization
      of 125I-labeled LPL at 37 degrees C was decreased when an excess of each of the
      three proteins was added to the culture medium, LPL was most effective.
      Furthermore, when LPL interaction with the 116-kDa binding protein was studied
      using ligand blots, 125I-labeled LPL binding was blocked only by unlabeled
      LPL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263412
TI  - Involvement of the lysosome in the catabolism of intracellular
      lysophosphatidylcholine and evidence for distinct pools of
      lysophosphatidylcholine.
AB  - The role of the lysosome in the metabolism of lysophosphatidylcholine was
      investigated in isolated rat hepatocytes. Chloroquine, primaquine, and ammonium
      chloride caused a 2.5-fold increase in radioactive lysophosphatidylcholine in
      [methyl-3H]choline-labeled cells. This effect was confirmed by a 1.7-fold
      increase in lysophosphatidylcholine mass in chloroquine-treated hepatocytes.
      Chloroquine caused a 2.7-fold increase in radioactive
      lysophosphatidylethanolamine in [1-3H]ethanolamine-labeled cells and a 2.3-fold
      increase in radioactive lysophosphatidylcholine in [methyl-3H]methionine-labeled
      cells. Chloroquine did not affect formation of choline-containing aqueous
      metabolites or the level of radioactivity in phosphatidylcholine (PC). The effect
      of chloroquine on radioactive lysophosphatidylcholine accumulation was
      concentration-dependent and occurred within 10 min, consistent with rapid
      inhibition of lysosomal function. As there was no observed decrease in the 3H in
      PC, the accumulation of lysophosphatidylcholine was likely due to the inhibition
      of acid lysophospholipase activity in chloroquine-treated cells. The accumulation
      of lysophosphatidylcholine in the presence of chloroquine was observed in both
      short-term- (30 min) and equilibrium-(24 h) [methyl-3H]choline-labeled cells.
      Simultaneous incubation of hepatocytes with both albumin and chloroquine
      increased the radioactivity in lysophosphatidylcholine in the medium
      independently of the accumulation of radioactive lysophosphatidylcholine in the
      cells. The results suggest that there are separate pools of
      lysophosphatidylcholine in the hepatocyte and that the pool donated to an
      extracellular acceptor is different from the lysosomal pool.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8263411
TI  - Interrelationships of alpha-tocopherol with plasma lipoproteins in African green
      monkeys: effects of dietary fats.
AB  - The distributions of plasma lipoprotein alpha-tocopherol and lipids were studied
      in African green monkeys consuming diets enriched in saturated, monounsaturated,
      or polyunsaturated fatty acids. Plasma total alpha-tocopherol concentrations were
      not different among the animals fed the three diets, whereas plasma total
      cholesterol concentrations were significantly different among the diet groups.
      The alpha-tocopherol: total lipid molar ratio in plasma high density lipoproteins
      (HDL) was significantly higher compared to low density lipoproteins (LDL) and
      very low plus intermediate-sized low density lipoprotein (VLDL + ILDL) of each
      diet group, suggesting that HDL may exhibit a greater affinity for alpha
      tocopherol. The presence of a positive correlation between HDL alpha-tocopherol
      and plasma apoA-I concentration and the absence of a correlation between HDL
      alpha-tocopherol and total lipid in HDL suggested that alpha-tocopherol
      associates with the protein moiety of HDL on the surface of the particle. A
      direct relationship between the plasma apoA-I: apoB molar ratio and the
      percentage of alpha-tocopherol found in the HDL fraction indicated that a greater
      proportion of alpha-tocopherol associates with HDL as the number of HDL particles
      in plasma increases relative to LDL particles. LDL from monkeys fed diets high in
      saturated fat contained 40% and 33% fewer alpha-tocopherol molecules per particle
      than LDL from monkeys fed polyunsaturated and monounsaturated fats, respectively.
      The phase transition temperature of LDL cholesteryl esters, indicative of the
      physical state of the lipids in the particle core, was well above body
      temperature in LDL from saturated fat-fed monkeys and was significantly higher
      compared to the other diet groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263413
TI  - Derivatization of bile acids with taurine for analysis by fast atom bombardment
      mass spectrometry with collision-induced fragmentation.
AB  - When analyzed by fast atom bombardment mass spectrometry, taurine-conjugated bile
      acids give intense [M-H]-pseudomolecular ions that can be subjected to collision
      induced fragmentation to give structural information. A method has been developed
      that permits rapid coupling of taurine to unconjugated, glycine-conjugated,
      sulfated, and glucuronidated bile acids. The reaction is performed for 2 h at
      room temperature in aqueous pyridine hydrochloride buffer, with or without
      dioxane, using 0.1 M 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as the
      coupling agent and 0.2 M taurine. The yields are higher than 95%. In contrast to
      published coupling reactions, the method permits conjugation of bile acids with
      the labile 7 alpha-hydroxy-3-oxo-4-ene structure.

PMID- 8263414
TI  - Hepatic expression of genes regulating lipid metabolism in rabbits.
AB  - The liver plays a central role in lipid metabolism and plasma lipoprotein
      homeostasis. This dynamic process is regulated by a variety of liver-derived
      proteins. However, the specific liver cells that express these proteins are
      largely unknown. In the current study we measured mRNA levels for 13 genes
      encoding proteins involved in lipid metabolism in isolated rabbit hepatic
      parenchymal and nonparenchymal cells. For these analyses we cloned partial rabbit
      cDNAs for apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), apolipoprotein E
      (apoE), cholesteryl ester transfer protein (CETP), hepatic lipase (HL),
      lipoprotein lipase (LPL), HMG-CoA reductase, LDL-receptor, 7 alpha-hydroxylase,
      albumin, bile salt-dependent cholesteryl ester hydrolase (CEH),
      lecithin:cholesterol acyl transferase (LCAT), and plasminogen activator inhibitor
      protein-1 (PAI-1). The cDNAs provided the basis for developing quantitative RNAse
      protection assays for each mRNA. These assays were used to determine whether
      differential patterns of mRNA expression existed between liver and other tissues
      and between hepatic parenchymal and nonparenchymal cells. The data demonstrate a
      diverse range in tissue distribution and mRNA abundance. Liver expressed all
      mRNAs except for LPL and CEH. Messenger RNA levels in isolated liver cell
      populations normalized to total RNA revealed a cell segregation pattern for
      hepatic gene expression: parenchymal cells showed higher levels of apoA-I, apoB,
      apoE, albumin, LCAT, HL, and 7 alpha-hydroxylase mRNAs compared to nonparenchymal
      cells while nonparenchymal cells showed higher levels of CETP, LDL-receptor, HMG
      CoA reductase, and PAI-1 mRNAs compared to parenchymal cells. These data
      demonstrate the existence of differential mRNA expression patterns in rabbit
      liver cell populations for genes encoding proteins affecting lipid metabolism.

PMID- 8263415
TI  - Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and
      related carnivores.
AB  - The biliary bile acid composition of gallbladder bile obtained from six species
      of bears (Ursidae), the Giant panda, the Red panda, and 11 related carnivores
      were determined by reversed phase liquid chromatography and gas chromatography
      mass spectrometry. Bile acids were conjugated solely with taurine (in N-acyl
      linkage) in all species. Ursodeoxycholic acid (3 alpha, 7 beta-dihydroxy-5 beta
      cholan-24-oic acid) was present in all Ursidae, averaging 1-39% of biliary bile
      acids depending on the species; it was not detected or present as a trace
      constituent (< 0.5%) in all other species, including the Giant panda.
      Ursodeoxycholic acid was present in 73 of 75 American Black bears, and its
      proportion averaged 34% (range 0-62%). Ursodeoxycholic acid averaged 17% of
      biliary bile acids in the Polar bear (n = 4) and 18% in the Brown bear (n = 6).
      Lower proportions (1-8%) were present in the Sun bear (n = 2), Ceylon Sloth bear
      (n = 1), and the Spectacled bear (n = 1). Bile of all species contained taurine
      conjugated chenodeoxycholic acid and cholic acid. In some related carnivores,
      deoxycholic acid, the 7-dehydroxylation product of cholic acid, was also present.
      To determine whether the 7 beta hydroxy group of ursodeoxycholic acid was formed
      by hepatic or bacterial enzymes, bile acids were determined in hepatic bile
      obtained from bears with chronic biliary fistulae. Fistula bile samples contained
      ursodeoxycholic acid, chenodeoxycholic acid, and a trace amount of cholic acid,
      all as taurine conjugates, indicating that ursodeoxycholic acid is a primary bile
      acid formed in the liver in Ursidae.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263416
TI  - Aggregation as well as chemical modification of LDL during oxidation is
      responsible for poor processing in macrophages.
AB  - Aggregation is a characteristic of extensively oxidized (ox-) LDL. We wished to
      determine whether this structural change contributed even more to the documented
      poor degradation in macrophages of ox-LDL than the chemical changes. When protein
      degradation of the soluble and insoluble portions of extensively ox-LDL was
      compared to that of acetyl LDL in mouse peritoneal macrophages (MPM), we found
      that the percent of internalized LDL that was degraded was lowest for the
      insoluble portion (insol. ox-LDL), intermediate for the soluble portion (sol. ox
      LDL), and highest for the acetyl LDL, regardless of whether the binding and
      uptake mechanisms had been excluded, e.g., by performing appropriate pulse-chase
      studies. As the same order of degradation was found after long-term degradation
      under cell-free conditions by a mixture of cathepsin B and D, it is likely that
      poor degradation of ox-LDL by lysosomal proteases is partially responsible for
      the deficient processing of ox-LDL in MPM. However, when MPM were incubated in a
      pulse-chase design with LDL that was induced to aggregate by vortexing without
      oxidizing (vx-LDL), degradation over an 18-h interval of accumulated vx-LDL was
      almost as low (25%) as that of insol. ox-LDL (18%), in contrast to sol. ox-LDL
      (60%). Yet, in a cell-free system cathepsin degradation of vx-LDL was as
      efficient as that of acetyl LDL and LDL. Also, the differences in degradation
      between sol. and insol. ox-LDL were smaller than in MPM. Thus, it appears that
      alternative mechanisms to poor proteolysis of substrate were responsible for poor
      intracellular processing of such aggregated lipoproteins. These results suggest
      that, although the poorer processing of insol. ox-LDL than sol. ox-LDL may be
      due, in part, to more deficient proteolytic degradation, particle aggregation per
      se may play at least as important a role in such deficiencies. This may occur by
      such mechanisms as altered intracellular trafficking leading to poorer fusion in
      macrophages of phagosomes containing aggregated lipoproteins with lysosomes.

PMID- 8263417
TI  - 14,15-Epoxyeicosatrienoic acid metabolism in endothelial cells.
AB  - Epoxyeicosatrienoic acid (EET) metabolism was studied in endothelial cells to
      determine whether this tissue may influence their vasoactive properties. Porcine
      aortic endothelial cells rapidly took up all four EET regioisomers. The uptake of
      [1-14C]14,15-EET reached a maximum in 15-30 min, and saturation was not observed
      with concentrations up to 5 microM. More than 70% of the incorporated 14,15-EET
      was contained in choline and inositol glycerophospholipids, most of it in the
      form of an EET ester. A metabolite, 14,15-dihydroxyeicosatrienoic acid (14,15
      DHET), accumulated in the medium during incubation, and products with similar
      chromatographic properties also were formed from 5,6-, 8,9-, and 11,12-EET. Much
      of the 14,15-EET taken up was only temporarily retained by the cells, and in 2 h
      half was released into the medium as 14,15-DHET. Bovine aortic and human
      umbilical vein endothelial cells also took up 14,15-EET, incorporated it into
      choline glycerophospholipids, and converted it to 14,15-DHET. These findings
      suggest that the endothelium may limit the vascular actions of EETs through rapid
      uptake, hydration, and release of DHETs into the circulation. Some vasoactive
      effects of EETs may result from their temporary accumulation in endothelial
      phospholipids involved in stimulus-response coupling.

PMID- 8263418
TI  - Differential incorporation of docosahexaenoic and arachidonic acids in frog
      retinal pigment epithelium.
AB  - Vertebrate retinas contain a high level of docosahexaenoic acid (DHA, 22:6n-3)
      and a relatively low level of arachidonic acid (AA, 20:4n-6). Although it is not
      known how DHA is selectively concentrated in the retina, the retinal pigment
      epithelium (RPE) is intimately involved in this process as these cells
      phagocytize shed rod outer segments (containing DHA) and take up DHA from the
      circulation. To explore the role of the RPE in the DHA enrichment in the retina,
      native frog RPE cells (RPE-eyecups) were incubated with [3H]DHA or [3H]AA for
      short times, or pulsed for up to 1 h with the two labeled fatty acids plus
      labeled glycerol simultaneously, followed by a chase for up to 7 h. The
      incorporation of label into various lipids was monitored by thin-layer or high
      performance liquid chromatography. In short-time incubations, a greater amount of
      DHA was incorporated into neutral lipids (primarily triglycerides, TG) compared
      with AA, while similar amounts of both fatty acids were found in phospholipids.
      On a relative basis, DHA was esterified mainly into TG, with AA into
      phospholipids. The uptake of each fatty acid correlated linearly with
      concentration (30-120 nM) and the incorporation pattern was distinct.
      Interestingly, the uptake and incorporation of labeled DHA or AA were not
      affected by the presence of unlabeled AA or DHA, respectively. In a pulse-chase
      experiment, RPE cells were active in the de novo synthesis of glycerolipids,
      particularly TG, which achieved a specific activity as high as diglycerides and
      ten times higher than the major phospholipids. The incorporation of DHA into most
      glycerolipids occurred to a large extent during de novo glycerolipid synthesis,
      whereas AA was incorporated mainly by deacylation-reacylation reactions. Our
      results suggest different metabolic pathways for handling DHA and AA in frog RPE.
      The preferential incorporation of DHA into TG suggests that TG might play an
      important role in the selective enrichment of DHA in the retina and in the
      recycling of photoreceptor DHA between the RPE and the retina.

PMID- 8263420
TI  - Expression of hormone-sensitive lipase mRNA in macrophages.
AB  - Macrophages contain a neutral cholesteryl ester hydrolase that can be activated
      by cAMP-dependent protein kinase. Immunological studies strongly suggest that
      hormone-sensitive lipase (HSL) is probably responsible for the cholesteryl ester
      hydrolase activity in macrophages; however, due to the very low level of
      expression in macrophages, it has been difficult to determine whether the
      macrophage cholesteryl ester hydrolase and adipose HSL are, in fact, products of
      the same gene. We have used the sensitive polymerase chain reaction (PCR)
      technique to demonstrate expression of HSL mRNA in resident and thioglycollate
      elicited mouse peritoneal macrophages, as well as in the P388D1 mouse macrophage
      cell line. PCR was performed using oligonucleotide primer sequences present on
      adjacent exons of the mouse HSL gene to allow discrimination between products
      derived from HSL mRNA or genomic DNA sequences; specificity of the PCR was
      demonstrated by the absence of a product in liver, which does not express HSL
      mRNA. Northern blot analysis of poly (A)+ RNA from peritoneal macrophages with a
      mouse adipose HSL cDNA probe demonstrated a low abundance of mRNA of 3.2 kb,
      identical in size to HSL mRNA in adipose tissue. These findings, together with
      the results of previous studies demonstrating similarities between HSL and
      macrophage neutral cholesteryl ester hydrolase, strongly support the conclusion
      that both are products of a single gene. The development of a PCR assay for HSL
      mRNA may allow further study of the regulation of neutral cholesteryl ester
      hydrolase expression in macrophages and foam cells, and its potential role in
      atherogenesis.

PMID- 8263419
TI  - Postprandial lipemia in subjects with hypobetalipoproteinemia and a single
      intestinal allele for apoB-48.
AB  - Hypobetalipoproteinemia in many kindreds is associated with truncated forms of
      apoB-100. Mutations of the apoB gene specifying more than 20 different carboxyl
      terminal truncations of apoB have been identified ranging in length from apoB-2
      to apoB-89. Truncations longer than apoB-48 appear to be secreted only by liver,
      while truncations shorter than apoB-48 are secreted by liver as well as
      intestine. Thus, intestines of subjects heterozygous for truncations > apoB-48
      contain two alleles producing apoB-48, while intestines of heterozygotes with
      truncations < apoB-48 contain only one allele producing apoB-48. Our aims were to
      assess whether intestinal fat absorption differed from normal in subjects with
      apoB-truncation-associated hypobetalipoproteinemia and whether fat absorption in
      heterozygotes with apoB < 48 differed from heterozygotes with apoB > 48. Ten
      subjects heterozygous for apoB > 48 (apoBs -89, -75, -54, -52), six heterozygous
      for apoB < 48 (apoBs -46, -40, -31) and a group of 16 controls matched for age,
      sex, body mass index characteristics, and eating similar diets were given
      identical fat meals containing vitamin A. Plasma triglycerides in whole plasma
      and retinyl palmitate in chylomicron and non-chylomicron (remnant) fractions were
      analyzed at zero time and over the next 14 hours. Fasting vitamins A and E also
      were quantified. Fasting plasma levels of vitamin E were lower in heterozygotes
      (536 +/- 198 mg/l for apoB > 48 vs. 372 +/- 155 for apoB < 48) versus controls
      (1162 +/- 441), but were not different when corrected for differences in LDL-C.
      Plasma vitamin A levels (uncorrected) were not different. Meal responses were
      characterized in terms of peak concentrations and areas under the curves (after
      subtraction of minimum points). These indices of fat absorption were comparable
      in all apoB phenotype groups suggesting that one allele specifying the intestinal
      production of apoB-48 is sufficient for normal fat absorption.

PMID- 8263421
TI  - Lovastatin enhances hepatic uptake of low density lipoprotein in humans.
AB  - A noninvasive method for visualizing the uptake of low density lipoprotein (LDL)
      was used to investigate the effect of hypolipidemic drugs on LDL uptake by the
      human liver in vivo. Fourteen hypercholesterolemic patients (six with familial
      hypercholesterolemia and eight with common hypercholesterolemia) were studied.
      Autologous LDL particles were isolated and divided into two aliquots; one was
      labeled with 99mTC and the other with 131I, and both preparations were reinjected
      simultaneously. The labeled LDL was visualized 24 h later by scanning the thorax
      and abdomen with a gamma camera, and the liver/heart ratio was calculated as an
      estimate of the hepatic uptake of LDL. The results of 99mTC-labeled LDL
      scintigraphy were compared with conventional determinations of the fractional
      catabolic rate (FCR) for 131I-labeled LDL. The latter correlated best with the
      liver/heart ratio (r = 0.80, P < 0.001). Lovastatin treatment increased the
      liver/heart ratio (15%, P < 0.01) in the patients with polygenic
      hypercholesterolemia and the FCR for LDL in both groups (22%, P < 0.05, for those
      with familial hypercholesterolemia and 37%, P < 0.01 for those with polygenic
      hypercholesterolemia). Scanning of the liver using the 99mTC-labeled LDL method
      provides a noninvasive method for visualizing the hepatic uptake of LDL in vivo
      in humans. This study also provides direct proof that lovastatin, a drug that
      enhances LDL receptor activity in the liver, also increases the hepatic uptake of
      LDL in humans.

PMID- 8263422
TI  - Measurement of total hepatic low density lipoprotein receptor levels in the
      hamster.
AB  - The ability to measure the total concentration of low density lipoprotein (LDL)
      receptors in hepatic tissues is of crucial importance to understanding changes in
      hepatic cholesterol metabolism. Such measurements can be made in conjunction with
      estimates of LDL receptor transcriptional activity, cell surface LDL receptor
      number, and rates of hepatic LDL uptake to evaluate the mechanisms controlling
      cellular LDL receptor expression. Current methods for assessing hepatic LDL
      receptor levels use microsomes as a source of LDL receptor, and thus rely on
      consistent contamination of the microsomal preparation with LDL receptor
      containing plasma membranes, endocytic vesicles, and/or secretory vesicles.
      Because this contamination is variable, and may vary with alterations in either
      the distribution of LDL receptors among the various cellular membrane fractions
      or in the composition of the intracellular membranes, measurement of LDL receptor
      concentration in microsomal fractions may not accurately reflect the total
      compliment of LDL receptors within the cell. We have developed the methodology
      for isolating the full complement of hepatic LDL receptor containing membranes by
      discontinuous sucrose density gradient centrifugation, and for quantitating LDL
      receptor concentration using a Western immunoblotting procedure that uses an anti
      C-terminal LDL receptor peptide polyclonal antiserum and assesses the intensity
      of color formation by reflectance densitometry. Using this methodology, we
      observed a 126 kDa immunoreactive band for the bovine adrenal cortex LDL receptor
      that also exhibited LDL binding activity as visualized by biotinylated LDL-ligand
      blotting, and a doublet of 140 kDa for the hamster liver LDL receptor. These
      bands were not observed when ligand blotting was conducted in the presence of
      either 10 mM EDTA or a 5-fold excess of unlabeled LDL, or when immunoblotting was
      conducted using either preimmune serum or antiserum that had been preabsorbed
      with LDL receptor peptide. The intensity of color formation was a linear function
      of the amount of membrane extract separated by electrophoresis. Intra-assay
      variation averaged 7%, and inter-animal variation averaged 20%. Cholestyramine,
      tiqueside, CP-88488, 17 alpha-ethinyl estradiol, mevinolin, and the combination
      of cholestyramine plus mevinolin, pharmacological interventions known to increase
      LDL receptor activity in experimental animals, produced the predicted increases
      in hamster total hepatic LDL receptor concentration that were highly correlated
      with concomitant increases in HMG-CoA reductase activity and reductions in serum
      cholesterol.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8263423
TI  - Hypochlorous acid-mediated modification of cholesterol and phospholipid: analysis
      of reaction products by gas chromatography-mass spectrometry.
AB  - Oxidative modification of membrane lipids by hypochlorous acid could be an
      important element in the mechanism of membrane disruption by activated
      neutrophils. We have previously shown that hypochlorous acid reacts with
      unsaturated fatty acids of membrane phospholipids to give fatty acid
      chlorohydrins (Winterbourn et al. 1992. Arch. Biochem. Biophys. 296: 547-555). In
      the present study, we examined the reaction of cholesterol in bilayers with an
      inert phospholipid carrier. Product separation and identification was performed
      using gas chromatography-mass spectrometry after trimethylsilyl-derivatization.
      Unlike the reaction of hypochlorous acid with unsaturated fatty acids, no
      chlorohydrin derivatives were found with cholesterol. Instead, the main oxidation
      products were identified as the epimeric cholesterol 5,6-epoxides and 4
      hydroxycholesterol, while several other hydroxy- and keto-derivatives were also
      found in smaller amounts. Analysis of the products obtained after reaction of
      vesicles composed of a mixture of several unsaturated phospholipid species plus
      cholesterol revealed that the individual fatty acids and cholesterol all exhibit
      comparable susceptibilities toward hypochlorous acid. Using myeloperoxidase to
      generate hypochlorous acid, basically the same products and product distribution
      were obtained. These studies show that unsaturated phospholipids and cholesterol
      can be profoundly modified by reaction with hypochlorous acid. This warrants
      further investigation to define the role of lipid modifications in neutrophil
      mediated membrane disruption.

PMID- 8263424
TI  - An n-level field theory of biological neural networks.
AB  - An n-level field theory, based on the concept of "functional interaction", is
      proposed for a description of the continuous dynamics of biological neural
      networks. A "functional interaction" describes the action from one substructure
      of a network to another at several levels of organization, molecular, synaptic,
      and neural. Because of the continuous representation of neurons and synapses,
      which constitute a hierarchical system, it is shown that the property of non
      locality leads to a non-local field operator in the field equations. In a
      hierarchical continuous system, the finite velocity of the functional interaction
      at the lower level implies non-locality at the higher level. Two other properties
      of the functional interaction are introduced in the formulation: the non-symmetry
      between sources and sinks, and the non-uniformity of the medium. Thus, it is
      shown that: (i) The coupling between topology and geometry can be introduced via
      two functions, the density of neurons at the neuronal level of organization, and
      the density-connectivity of synapses between two points of the neural space at
      the synaptic level of organization. With densities chosen as Dirac functions at
      regularly spaced points, the dynamics of a discrete network becomes a particular
      case of the n-level field theory. (ii) The dynamics at each of the molecular and
      synaptic lower level are introduced, at the next upper level, both in the source
      and in the non-local interaction of the field to integrate the dynamics at the
      neural level. (iii) New learning rules are deduced from the structure of the
      field equations: Hebbian rules result from strictly local activation; non-Hebbian
      rules result from homosynaptic activation with strict heterosynaptic effects,
      i.e., when an activated synaptic pathway affects the efficacy of a non-activated
      one; non-Hebbian rules and/or non-linearities result from the structure of the
      interaction operator and/or the internal biochemical kinetics.

PMID- 8263425
TI  - Estimating selective advantage of two alleles in discrete time.
AB  - A class of estimators for the selective advantage, s, in a Wright-Fisher model
      with two alleles, variable population size, and genic selection is derived via
      martingale theory. Explicit expressions are given for these estimators which only
      involve simple computation. The optimal estimate among this class of estimators
      is obtained. Asymptotic results are readily established by an application of a
      martingale central limit theorem. The performance of this optimal estimator is
      compared to known estimators by means of a simulation study.

PMID- 8263426
TI  - A note on modelling the dynamics of budding yeast populations using branching
      processes.
AB  - A multitype branching process is proposed as a model for the behaviour of
      populations of the budding yeast Saccharomyces Cerevisiae. Using the idea of
      branching processes counted by random characteristics, we are able to obtain
      explicit expressions describing different aspects of the asymptotic composition
      of such populations. The main purpose of this note is to show that the branching
      process approach is an alternative to deterministic population models based on
      differential equation methods.

PMID- 8263427
TI  - Numerical solution of structured population models. I. Age structure.
AB  - Numerical methods are presented for a general age-structured population model
      with demographic rates depending on age and the total population size. The
      accuracy of these methods is established by solving problems for which alternate
      solution techniques are available and are used for comparison. The methods
      reliably solve test problems with a variety of dynamic behavior. Simulations of a
      blowfly population exhibit cyclic fluctuations, whereas a simulated squirrel
      population reaches a stable age distribution and stable equilibrium population
      size. Life-history attributes are easily studied from the computed solutions, and
      are discussed for these examples. Recovery of a stressed population back to
      equilibrium is examined by computing the transition in age structure, and the
      transient behavior of other properties of the population such as the per capita
      growth rate, the average age, and the generation length.

PMID- 8263428
TI  - The coalescent in two colonies with symmetric migration.
AB  - Kingman's coalescent process is extended to two colonies with symmetric
      migration. The mean waiting time until a sample of genes taken from two colonies
      coalesces to a common ancestor is obtained. The final step in the waiting time
      before the process is absorbed at 1 is observed to have an intriguing behaviour.
      The distribution of this final waiting time converges to the known distribution
      of the corresponding waiting time in the case of a single population as the
      migration rate tends to zero. The mean, however, does not converge. The waiting
      time until a sample has two common ancestors is modeled as a function of the
      migration rate. Finally bounds for the expected waiting time for the two colonies
      to have j > l ancestors are derived.

PMID- 8263429
TI  - A mathematical model for the force and energetics in competitive running.
AB  - A simple mathematical model for competitive running is developed. This model
      contains the force and energy reserves as key variables and it described their
      relationship and dynamics. It is made up of three submodels for the biomechanics
      of running the energetics and the optimization. The model for the energetics is
      an extension of the hydraulic model of Margaria and Morton. The key geometric
      parameters of this piecewise linear, three compartment model are determined on
      the basis of well known physiological facts and data.

PMID- 8263430
TI  - The reliability of patient positioning for evaluating static radiologic
      parameters of the human pelvis.
AB  - OBJECTIVE: To determine the reproducibility of patient positioning on
      radiographically evaluated static configurations of the human pelvis. DESIGN:
      Repeat anteroposterior radiography of the human pelvis was performed in vivo.
      Comparative examinations were performed after 1 hr in one subject pool. A second
      sample underwent repeat examination after a mean of 18 days. SETTING: Outpatient
      private practice chiropractic clinic. SUBJECTS: Thirty-seven relatively
      asymptomatic subjects participated in the experiment. MAIN OUTCOME MEASURES:
      Millimetric evaluations were made for leg length inequality, right/left sacral
      discrepancies and right/left innominate differences. The null hypothesis was that
      the difference of the measurements from the two radiographs would be equal to
      zero. A paired t-test was used to analyze if there were any significant
      differences. The mean measured difference in millimeters and correlation
      coefficients were also determined for each variable. RESULTS: Individual
      variations for several roentgenometric parameters, including leg length
      inequality and pelvic torsion, did not reach statistical significance (p > .05)
      although minor millimetric discrepancies were recorded. Correlation coefficients,
      in most cases, were relatively high. CONCLUSION: A subject can be reliably
      positioned for repeat anteroposterior pelvic radiography for both 1 hr and 18-day
      intervals. The methodology described has applicability to full spine radiography
      when roentgenometric parameters of the pelvis are scrutinized.

PMID- 8263431
TI  - Cavitation sounds during spinal manipulative treatments.
AB  - OBJECTIVE: The purpose of this study was to confirm a practitioner's perception
      of cavitation during spinal manipulative therapy in a clinically relevant
      situation using accelerometer recordings. DESIGN: Experimental study. SETTING:
      Human Performance Laboratory and Sports Medicine Center, University of Calgary.
      PARTICIPANTS: Twenty-eight patients from a single practitioner's patient pool who
      had pain in the area of the thoracic spine. INTERVENTION: Spinal manipulative
      treatment (SMT) on the transverse process of T4 using a reinforced unilateral
      contact and delivering a thrust in the posterior to anterior direction. MAIN
      OUTCOME MEASURES: Instantaneous acceleration signals obtained from the spinous
      process of T3 during SMT and the practitioner's perception if cavitation had
      occurred or not at the end of each treatment. CONCLUSIONS: It appears that
      cavitation may be measured during SMT using accelerometry and that a
      practitioner's perception of the occurrence of cavitation during SMT is very
      accurate.

PMID- 8263432
TI  - The age-related advancement of arterial disease measured by Doppler ultrasound
      diastolic flow analysis.
AB  - OBJECTIVE: To quantify by A-mode Doppler sonography the age-related progression
      of arterial disease so that age dependent normal values may be established for
      the screening Doppler peripheral arterial exam. Arterial distensibility was
      assessed by A-mode Doppler diastolic flow analysis as a measure of atherogenesis.
      These values will increase the sensitivity and decrease the incidence of false
      positive results when the Doppler exam is utilized to differentially diagnosis
      vascular and sciatic neurogenic claudication. The relationship between age and
      results from the standard ankle/arm index ultrasound pneumatic cuff examination
      was also analyzed. DESIGN: A two by three analysis of variance with orthogonal
      Helmert contrast codes and simple linear regression analysis was utilized for
      this cross-sectionally designed investigation. The dependent measures of
      diastolic flow analysis and ankle/arm pressure index were obtained within three
      nested successively increasing age groups. SETTING: Chiropractic office.
      SUBJECTS: Studied were a total of 90 sedentary nonsmoking subjects, aged 23-79
      yr, all of whom had normally accepted levels of serum glucose, cholesterol and
      blood pressure. Subjects were screened for evidence of aortic coarctation,
      myocardial infarction, tachyarrhythmia, aortic valve stenosis, mitral prolapse,
      hypertension, hypercholesterolemia, diabetes and peripheral occlusive arterial
      disease. Anthropometric measurements and percent body fat were obtained. A
      predictive oxygen consumption bike ergometer test was performed to obtain aerobic
      capacity. The commonly utilized standard ankle/arm index ultrasound pneumatic
      cuff examination and arterial diastolic flow analysis were performed with A-mode
      Doppler ultrasound on all subjects. RESULTS: These results demonstrate that a
      significant inverse linear relationship exists between aging and arterial
      compliance (p < .0001) in our population. Diastolic flow analysis had a greater
      sensitivity to arterial disease than the standard ankle/arm index ultrasound
      pneumatic cuff procedure. CONCLUSION: When utilizing A-mode Doppler ultrasound
      diastolic flow analysis as an indicator of early peripheral atherosclerotic
      arterial disease, increased sensitivity may be obtained when the age-related
      elevation in atherogenesis is taken into account.

PMID- 8263433
TI  - Neglected spinal cord, brain stem and musculoskeletal injuries stemming from
      birth trauma.
AB  - OBJECTIVE: A review of the medical literature was undertaken to determine cause,
      diagnosis, prognosis, treatment and prevention of injuries resulting from birth
      trauma. The primary focus was the neonate, though infant, child and adult were
      also considered because the effects of birth trauma can be life-long. DATA
      SOURCE: A compilation of case studies and review articles were extracted from
      numerous "MEDLINE" literature searches. Key Terms included: Birth Trauma, Central
      Nervous System Injuries, Musculoskeletal Injuries, Stillbirth, Sudden Infant
      Death Syndrome (SIDS), Cerebral Palsy, Brachial Plexus Palsies (Erb's and
      Klumpke's), Neonatal-Infantile Respiratory Distress, Obstetric Accidents
      (Forceps, Vacuum Cup and Cesarean Deliveries), Subluxation, Chiropractic
      Treatment. American, British, Danish and German studies were included to show the
      universality of the problem. STUDY SELECTION: Findings were selected on the basis
      of a clear connection between birth trauma and the resulting symptoms, syndromes
      and/or death. DATA EXTRACTION: Findings were compiled by studying articles from
      the literature search. The quality and validity were assessed by corresponding
      references, method of documentation, number of case studies, length of time over
      which studies took place and presence of follow-up documentation. DATA SYNTHESIS:
      Inadequacies and source discrepancies were also included with regard to cause and
      types of obstetric accidents. CONCLUSION: Birth trauma remains an underpublicized
      and, therefore, an undertreated problem. There is a need for further
      documentation and especially more studies directed toward prevention. In the
      meantime, manual treatment of birth trauma injuries to the neuromusculoskeletal
      system could be beneficial to many patients not now receiving such treatment, and
      it is well within the means of current practice in chiropractic and manual
      medicine.

PMID- 8263434
TI  - Chiropractic management of a hypertensive patient.
AB  - OBJECTIVE: Although many chiropractors may treat patients who have concomitant
      hypertensive disease, there is a paucity of literature on the nuances of case
      management for these patients. We report a patient who underwent a course of
      chiropractic care with a previous diagnosis of chronic essential hypertension.
      CLINICAL FEATURES: A 38-yr-old male presented for chiropractic care with
      complaints of hypertension, drug-related side effects and lower back pain. He was
      also receiving concurrent medical care for his hypertension. INTERVENTION AND
      OUTCOME: The patient received specific contact, short lever arm spinal
      adjustments as the primary mode of chiropractic care. During the course of
      chiropractic treatment, the patient's need for hypertensive medication was
      reduced. The patient's medical physician gradually withdrew the medication over 2
      months. CONCLUSION: Specific contact short lever arm spinal adjustments may cause
      a hypotensive effect in a medicated hypertensive patient that may lead to
      complications (e.g., hypotension). Since a medicated hypertensive patient's blood
      pressure may fall below normal while he or she is undergoing chiropractic care,
      it is advised that the blood pressure be closely monitored and medications
      adjusted, if necessary, by the patient's medical physician.

PMID- 8263435
TI  - Chiropractic adjustment to the cervical spine and the Arnold-Chiari malformation.
AB  - OBJECTIVE: To present two cases in which patients with Type I Arnold-Chiari
      malformation (ACM) were treated with adjustments to the cervical spine for
      conditions unrelated to the anomaly. CLINICAL FEATURES: The ACM is an anomaly of
      central nervous system development in which structures from the posterior fossa
      descend below the level of the foramen magnum. INTERVENTION AND OUTCOME: The
      patients reported were adjusted multiple times to the cervical spine. No ill
      effects or complications were noted related to the ACM. CONCLUSIONS: Asymptomatic
      Type I ACM is not necessarily a contraindication to skilled adjustments to the
      cervical spine.

PMID- 8263436
TI  - Chiropractic correction of congenital muscular torticollis.
AB  - OBJECTIVE: To present a case of congenital muscular torticollis and discuss the
      clinical manifestations and chiropractic treatment. CLINICAL FEATURES: A 7-month
      old male infant with significant head tilt since birth was brought to a
      chiropractic physician for evaluation. The infant's history included ear
      infections, facial asymmetry and regurgitation. Significant spasm of the left
      sternocleidomastoid and trapezius muscles, a left lateral atlas and suboccipital
      joint dysfunctions were present upon examination. A diagnosis of congenital
      muscular torticollis was made. INTERVENTION AND OUTCOME: Treatments included
      chiropractic manipulation, trigger point therapy, specific stretches, pillow
      positioning and exercises. Excellent results were obtained. CONCLUSION: Suggests
      that chiropractic intervention is a viable treatment option for congenital
      muscular torticollis. Further studies should be performed to compare the
      effectiveness of other treatment options.

PMID- 8263437
TI  - Correlation study on infrared thermography and nerve root signs in lumbar
      intervertebral disk herniation patient: a short report.

PMID- 8263438
TI  - Effects of calcium phosphate solutions on dentin permeability.
AB  - Calcium phosphate solutions at various concentrations and pH levels were used to
      obstruct the dentinal tubules. The effects were evaluated by measurements of
      permeability through dentin discs and by scanning electron microscopy.
      Precipitation kinetics were followed by pH changes in the solutions and products
      were determined by X-ray powder diffraction. The solutions were applied in two
      ways: (a) calcium and phosphate solutions were mixed before application and (b)
      one solution (calcium or phosphate) was applied first followed by the other
      solution. Three kinds of human dentin discs were used; one with smear layer and
      the other two with tubules exposed by sonication or etched by acid. The high
      concentration calcium phosphate solutions at pH = 9.5 rapidly precipitated
      amorphous calcium phosphates that obstructed the dentinal tubules and decreased
      dentin permeability by 85% or more. At pH = 5.6, the calcium phosphate solutions
      precipitated large crystals of dicalcium phosphate dihydrate. In this case, the
      effectiveness in obstructing dentinal tubules was found to be procedure
      sensitive.

PMID- 8263439
TI  - An evaluation of three materials as barriers to coronal microleakage in
      endodontically treated teeth.
AB  - Barrier Dentin Sealant, glass ionomer cement, and TERM were evaluated as possible
      barriers to coronal microleakage. The root canals of 70 extracted teeth were
      accessed, cleaned and shaped, and then obturated with gutta-percha and sealer.
      The teeth were divided into four groups, one for each barrier material evaluated
      and one control group. Subgroups were stored in a humidor or immersed in
      artificial saliva for 7 days and then placed in methylene blue dye. Barrier
      Dentin Sealant and TERM groups demonstrated the lowest dye penetration
      measurements. The difference between them was not statistically different. Glass
      ionomer cement demonstrated the greatest dye penetration and was statistically
      different from the other two barrier materials.

PMID- 8263440
TI  - An evaluation of the durability of apex locator insulated probes after
      autoclaving.
AB  - The purpose of this study was to evaluate the durability of insulated probes
      designed to be used with the Endocater Apex Locator when put through multiple
      cleaning and autoclaving cycles. The manufacturer has reported that the plastic
      coating on the probes is reliable with normal use and sterilizable up to a
      maximum of three cycles. The quality of the seal provided against electrical
      conductivity by the coating was evaluated using 60 probes of various sizes (10,
      15, 20, 25, 40) before and after autoclaving. Visual and electrical field methods
      were used to detect any leakage in the insulated coating. Defects were detected
      electronically before they could be detected visually. Statistically significant
      differences in millimeters of coating lost were found between the original
      evaluation and after each autoclaving cycle. The size 40 probes lost
      statistically significantly more coating than did any of the other sizes. The
      loss of coating seemed to be related to the millimeter markings. The quality of
      the probes as they came from the manufacturer was excellent; no defects were
      found in the coating prior to autoclaving.

PMID- 8263441
TI  - Elongation and movement of the gutta-percha master cone during initial lateral
      condensation.
AB  - This study evaluated gutta-percha master cone elongation and apical movement
      during initial lateral condensation. A split natural tooth model was used.
      Measurements on photographs taken before and after initial spreading were made.
      The results showed that both elongation and total cone displacement occur.

PMID- 8263442
TI  - Leakage evaluation with and without vacuum of two gutta-percha fill techniques.
AB  - Two sets of 30 roots were obturated either with lateral condensation or a
      halothane dip technique. Fifteen roots from each group were immersed in India ink
      with vacuum and 15 without vacuum. Each root was coated with nail polish and wax,
      leaving only its apical end open for ink penetration. The roots were cleared and
      three linear measurements were made: distance of ink penetration coronal to the
      gutta-percha apical tip; distance from the gutta-percha tip to major foramen; and
      distance from the major foramen to anatomical apex. The average length of ink
      penetration coronal to the apical extension of the gutta-percha for the lateral
      condensation groups combined was 1.33 mm and for the halothane groups combined
      was 2.15 mm. There was no significant difference between vacuumed and not
      vacuumed for degree of ink penetration. The gutta-percha of the halothane-dipped
      groups advanced significantly closer to the foramen than the lateral condensation
      groups (0.38 mm versus 0.65 mm).

PMID- 8263443
TI  - Effect of three obturation techniques on the filling of lateral canals and the
      main canal.
AB  - The three-dimensional obturation of the root canal system is widely accepted as a
      key factor for successful endodontic therapy. The purpose of this study was to
      evaluate the obturation of lateral canals and the main canal using three gutta
      percha sealer techniques: cold lateral condensation, warm lateral condensation,
      and warm vertical condensation. Sixty epoxied blocks with five lateral canals
      placed at varying angles from the main canal were used. Each experimental group
      was treated by a board-certified endodontist with training and clinical
      experience in that obturation technique. There was no statistically significant
      difference (p < 0.05) between the obturation techniques in the ratio of the void
      area to the gutta-percha-plus-sealer area for the main canal. There was
      significantly (p < 0.001) more sealer in the lateral canals for the two lateral
      condensation techniques. The warm obturation techniques had significantly (p <
      0.001) more gutta-percha in the lateral canals.

PMID- 8263444
TI  - Evaluation of the effectiveness and comfort of incisive nerve anesthesia given
      inside or outside the mental foramen.
AB  - Thirty volunteer subjects were given bilateral injections of one-half carpule of
      2% Xylocaine with 1:100,000 epinephrine to anesthetize the incisive nerve.
      Injections were given either inside or outside the mental foramen. Success (80/80
      reading) and duration of anesthesia were verified with the Analytic Technology
      pulp tester. Pain and preference for either injection type were evaluated via
      questionnaire. The mental foramen could be located in 1 min 56.6% of the time.
      There was a significantly greater chance of success for injections given inside
      the foramen for the second bicuspid (p = 0.0422) and the canine (p = 0.015).
      There was no statistically significant difference in success for either type
      injection for the first bicuspid (p = 0.184). There was no significant difference
      in duration of anesthesia whether given inside or outside the foramen and no
      difference in pain of injection with either type. Patients had no clear-cut
      preference for either injection type.

PMID- 8263445
TI  - Successful single-visit endodontics during Operation Desert Shield.
AB  - This article reports on the incidence of success following single-visit
      endodontic therapy. Non-surgical endodontic therapy was performed on 210 teeth in
      167 patients who were rapidly deployed during the initial stages of Operation
      Desert Shield. Upon their return, 97 patients were recalled for follow-up
      evaluation. This study evaluated 102 teeth. The recall rate was 58% with a
      success rate of 89%.

PMID- 8263446
TI  - Two approaches to the treatment of true combined periodontal-endodontal lesions.
AB  - Periodontal endodontal lesions present a difficult diagnostic and treatment
      challenge to the clinician and treatment often requires a combined therapeutic
      effort. Both endodontal and periodontal surgical procedures may be indicated for
      access and treatment of these lesions. This case report presents an early onset
      periodontitis patient with bilateral periodontal-endodontal lesions on mandibular
      first molars. Treatment included apical surgery followed by repeated scaling and
      root planing on one tooth and root canal obturation followed by a periodontal
      bone grafting procedure on the other. Both procedures resulted in clinical
      attachment gain as well as radiographic evidence of alveolar bone gain. This case
      report once again demonstrates that proper diagnosis followed by removal of
      etiologic factors and nonsurgical therapy or periodontal regenerative procedures
      can restore health and function in cases of severe attachment loss.

PMID- 8263447
TI  - Retrievability of Thermafil plastic cores using organic solvents.
AB  - Twenty distal roots of extracted mandibular first and second molars were
      instrumented, then obturated using Thermafil obturating material with solid
      plastic core carriers. To simulate a retreatment process, the gutta-percha was
      softened using one of four solvents, chloroform, xylene, eucalyptol, or
      halothane. A K file was used to advance the solvent into the gutta-percha and to
      engage the plastic carrier. In all but one case, the plastic carriers were easily
      removed from the root canal. It was concluded that the plastic carriers used with
      the Thermafil obturation media do not present a difficult obstacle for removal
      should the root require retreatment.

PMID- 8263448
TI  - Should we be teaching endodontics to general dentists?

PMID- 8263449
TI  - An evaluation of the effect of methylene blue dye pH on apical leakage.
AB  - The effect of varying the pH of 2% methylene blue dye on apical leakage was
      evaluated. Eighty-four roots of extracted human teeth were used in this study.
      The roots were endodontically cleaned and shaped, obturated, apically resected,
      and amalgam or Temporary Endodontic Restorative Material retro-fillings were
      placed. The roots were immersed for 7 days in dye solutions of controlled pH of
      1, 2, 3, 5 or 7, or in a 2% unbuffered deionized water solution of methylene
      blue. The results demonstrated significantly less leakage in the pH 1 and 2
      amalgam groups. All other amalgam groups and the Temporary Endodontic Restorative
      Material groups showed no significant differences attributable to pH. Temporary
      Endodontic Restorative Material retrofilling groups demonstrated statistically
      significantly less apical leakage at each pH evaluated than the amalgam
      retrofilled groups. Additionally, a significant buffering effect of the root
      structure on the dye solutions was measured.

PMID- 8263450
TI  - Bending and metallurgical properties of rotary endodontic instruments. IV. Gates
      Glidden and Peeso drills.
AB  - A laboratory study was performed on Gates Glidden and Peeso drills to determine
      the bending characteristics and related metallurgical properties. Sizes #1 to #6
      stainless steel Gates Glidden drills, sizes #1 to #6 stainless steel and carbon
      steel type P Peeso drills, and sizes #009 to #023 carbon steel-type B-1 Peeso
      drills were evaluated in cantilever bending with a Tinius Olsen stiffness tester.
      The bending moments were measured for a 12.5-mm test span at deflection angles of
      2 to 90 degrees. The mean maximum bending moments in g cm and the corresponding
      deflection angles in degrees were plotted graphically to ascertain the bending
      characteristics of the instruments. The stainless steel Gates Glidden and Peeso
      drills exhibited considerable permanent bending deformation during testing. Some
      stainless steel drill samples were able to withstand the full bending deflection
      of 90 degrees without fracturing. In contrast, the carbon steel Peeso drills were
      able only to undergo bending deflections of less than 20 degrees and exhibited
      brittle fracture. If the drill fractured during the in vitro testing, the failure
      site was always located near the handpiece end.

PMID- 8263451
TI  - Effect of restoration thickness on the sealing ability of TERM.
AB  - An in vitro study was done using a fluid filtration device to compare
      microleakage of Temporary Endodontic Restorative Material (TERM) at various
      thicknesses. Forty-four extracted mandibular molars had their roots removed at
      the cementoenamel junction, occlusal table flattened, and a standardized
      endodontic access made in the crown. The teeth were restored with TERM in
      thicknesses of 1, 2, 3, and 4 mm, and quantitatively measured for leakage
      (microliters/min) at intervals of 1 and 24 h and 1, 3, and 5 wk. Thermocycling
      was accomplished at the 5-wk interval. Positive controls received 4-mm-thick IRM
      or gutta-percha restorations and were measured at 24 h only. Repeated measures of
      analysis of variance found no significant difference (p < 0.05) in leakage values
      in any group over time or between any of the different thicknesses. Positive
      controls showed significantly more leakage than all other groups. TERM maintained
      as tight a seal at 1-, 2-, and 3-mm thicknesses as it did at 4 mm and may be
      suited for clinical situations where less than 4 mm of restorative space exists.

PMID- 8263452
TI  - Cleaning of oval canals using ultrasonic or sonic instrumentation.
AB  - This study investigated the effect of direction of file oscillation on the amount
      of debris and smear remaining within oval canals. Sixty-five lower premolars were
      allocated to six experimental groups (n = 10) and one control group (n = 5).
      Canals were prepared using Gates Glidden burs and hand instruments. Preparations
      were completed using either an ultrasonic size 15 K file or a sonic size 15
      shaper file. Three preparation techniques were used: (a) file oscillation toward
      oval recesses within the canal, (b) file oscillation at right angles to the
      recesses, and (c) rotational movement of handpiece. Canals were examined under
      the scanning electron microscope and blindly scored for debris and smear layer.
      Log linear analysis revealed no significant difference (p > 0.05) between sonic
      or ultrasonic instrumentation as to debris or smear layer remaining. File
      oscillation directed toward oval recesses left the least amount of debris (p <
      0.05). Smear layer remained unaffected by all techniques.

PMID- 8263453
TI  - Human saliva penetration of coronally unsealed obturated root canals.
AB  - Studies have shown significant coronal dye and bacterial leakage following
      exposure of sealed root canals to artificial and natural saliva. The purpose of
      this study was to determine the time needed for bacteria in natural saliva to
      contaminate the entire length of root canals obturated by lateral and vertical
      condensation techniques. Forty root canals were cleaned and shaped using a step
      back technique. Thirty root canals were obturated with gutta-percha and root
      canal sealer using either lateral or vertical condensation techniques. Forty root
      canals were obturated without a root canal sealer and served as positive
      controls. After obturation, the coronal 3 mm of five root canals were sealed with
      sticky wax and served as negative controls. The coronal portions of the filling
      materials were placed in contact with human saliva and the number of days
      required for bacteria in saliva to penetrate the entire root canals were
      determined. No bacterial leakage occurred in the negative control group. Complete
      bacterial leakage occurred within 2 days in the positive control group. All root
      canals were recontaminated in less than 30 days. No statistical significant
      difference was found between the two methods of obturation.

PMID- 8263454
TI  - Responses of osteoblastic cells (UMR 106) exposed to elevated extracellular
      calcium.
AB  - Bone cells can be exposed to high calcium in the course of endodontic treatment.
      To investigate the effects of high calcium on bone cell function, responses of a
      rat osteoblast cell line (UMR 106) were examined. Responsiveness of the cells to
      parathyroid hormone, prostaglandin F1 alpha, and ionomycin was assessed by
      measuring calcium transients elicited by these stimuli. Raising the medium
      calcium from 1.8 to 50 mM did not alter cell responsiveness. Pretreatment of the
      cells with the calcium pump inhibitor sodium vanadate prevented parathyroid
      hormone effects and slightly decreased prostaglandin F1 alpha effects in both
      normal and high calcium. The effect of ionomycin was prolonged in high calcium
      when vanadate was present. The results suggest that cells of the osteoblast
      phenotype can maintain calcium signaling in the presence of high extracellular
      calcium. These processes could play a role in the therapeutic effectiveness of
      high calcium in endodontic treatment.

PMID- 8263455
TI  - Prophylactic penicillin: effect on posttreatment symptoms following root canal
      treatment of asymptomatic periapical pathosis.
AB  - It has been reported that administration of prophylactic penicillin may prevent
      flare-ups or other undesirable posttreatment sequelae following root canal
      treatment. To test this hypothesis in a prospective study, 80 patients with a
      diagnosis of pulp necrosis and chronic apical periodontitis were divided into
      three groups: group A (prophylactic penicillin, AHA recommendation), group B
      (placebo, same regimen), and group C (no medication). Medications and evaluations
      were double-blinded. Patients reported their posttreatment events including
      incidence of flare-ups, incidence and severity of pain/swelling, and occurrence
      of adverse side effects. Differences in the three groups were determined
      statistically using chi-square tests. The outcome showed no significant
      difference (p = 0.68) among the three groups. That is,
      administration/nonadministration of penicillin prophylactically was unrelated to
      posttreatment signs and symptoms following canal preparation. Incidence of flare
      ups was very low (1 of 80). Occurrence of pain in the mild-moderate levels was
      fairly high (approximately 70% overall), but was primarily in the mild category.
      Overall incidence of side effects was also very low (2 of 80). Severe levels of
      pain/swelling and flare-up incidence were low with no difference between
      administration or nonadministration of antibiotics. Based on our data, using
      penicillin (a potentially dangerous drug) prophylactically to control
      posttreatment symptoms is not recommended in cases of pulp necrosis and
      asymptomatic periapical pathosis.

PMID- 8263456
TI  - A retrospective study of endodontically treated mandibular first molars in a
      Chinese population.
AB  - The purpose of this investigation was to study the prevalence of three roots and
      four root canals in the mandibular first molars of a Chinese population. A total
      of 832 cases of mandibular first molars that had received root canal treatment
      clinically were examined by reviewing the clinical records and radiographs. The
      results showed that: (a) Mandibular first molars with four root canals occur at a
      frequency of 31.5%. (b) More than two-thirds (68.3%) of the above cases had the
      fourth canal arising from the third root, an extradistal root. (c) The bilateral
      occurrence of this extradistal root in mandibular first molars was 67%. In
      conclusion, the occurrence of four root canals in mandibular first molars among
      Chinese people was not unusual.

PMID- 8263457
TI  - Obturation of a C-shaped canal using an improved method of warm lateral
      condensation.
AB  - Pilot studies conducted by the authors seem to indicate that obturation of a root
      canal system by the lateral condensation of gutta-percha using an electrically
      heated spreader results in a more homogeneous mass of gutta-percha than standard
      lateral condensation. This article describes an improved variation which prevents
      inadvertent dislodgement of the mass of gutta-percha during the obturation. The
      authors refer to this technique as "zap and tap" and a case report describes its
      use to obturate a C-shaped canal system of a mandibular second molar.

PMID- 8263459
TI  - How to write the result section of a scientific paper.

PMID- 8263458
TI  - Using a 1-ml syringe for the chloroform dip root canal filling technique.
AB  - This article describes using a 1-ml syringe as an alternative to a dappen dish to
      hold chloroform during the chloroform dip root canal filling technique. The
      syringe effectively holds chloroform while limiting its exposure to the
      endodontic operatory air.

PMID- 8263460
TI  - The scientific article. Discussion section.

PMID- 8263461
TI  - References in a scientific paper.

PMID- 8263462
TI  - New products in endodontics. False claims by manufacturers or endodontist
      paranoia?

PMID- 8263463
TI  - A unified account of cognitive impairments following frontal lobe damage: the
      role of working memory in complex, organized behavior.
AB  - A computer model is presented that performs 4 tasks sometimes impaired by frontal
      damage: motor sequencing, the Stroop task, the Wisconsin Card Sorting Test, and a
      context memory task. In each task, patterns of performance typical of frontal
      damaged patients are shown to result from the same type of damage to the model,
      specifically, weakening of associations among elements in working memory. The
      simulation shows how a single underlying type of damage could result in
      impairments on a variety of seemingly distinct tasks. Furthermore, the
      hypothesized damage affects the processing components that carry out the task
      rather than a distinct central executive.

PMID- 8263464
TI  - Resistance to extinction of fear-relevant stimuli: preparedness or selective
      sensitization?
AB  - Human conditioning research has revealed an apparent resistance to extinction of
      aversive conditioning to pictures of fear-relevant stimuli such as snakes and
      spiders, supporting M. E. P. Seligman's (1971) preparedness theory of fears and
      phobias. This article examines an alternative account based on activation of
      preexisting response tendencies under threat (selective sensitization). Two
      experiments demonstrate that selective sensitization of electrodermal responses
      is attenuated when a fear-relevant stimulus serves as a negative conditioned
      stimulus (CS-), but is maintained when it serves as a positive conditioned
      stimulus (CS+). Previous extinction results may therefore be due to preservation
      of initial responding to CS+ but not CS-. Selective sensitization offers a model
      for the nonassociative activation of fears and phobias to prepotent stimuli under
      conditions of stress or threat. Possible genetic and cognitive mechanisms are
      discussed.

PMID- 8263465
TI  - Categories and resemblance.
AB  - Many theories of concepts link categorizing to similarity. If a new instance is
      sufficiently similar to category members, then the instance is likely to be a
      member itself. However, judged similarity are judged category likelihood
      sometimes diverge. In these studies, we describe frequency distributions for
      categories that vary along a single dimension, and ask Ss to rate the similarity,
      typicality, or category likelihood of instances along this continuum. The average
      ratings exhibit distinct patterns, with category likelihood depending on the
      instance's frequency and with similarity depending on distance from the instance
      to the center of the distribution. Typicality ratings show effects of both
      frequency and distance. These differences occur for bimodal distributions
      (Experiments 1 and 2) and for unimodal ones (Experiment 3). They appear both when
      we present the distributions as histograms and when we imply them in
      descriptions. We argue that similarity-based models of categorizing are
      incomplete and may apply mainly to situations in which more definitive
      information is unavailable.

PMID- 8263466
TI  - Effect of melatonin on pituitary secretion of prolactin in vitro during delayed
      implantation and the periimplantation period in the spotted skunk.
AB  - The pars tuberalis of the western spotted skunk is the only region of the brain
      known to bind 2-[125I]iodomelatonin, thus suggesting that this region of the
      pituitary might be essential in mediating the effects of melatonin in this
      species. Female skunks were killed during short- and long-day photoperiods.
      Hemisections of the adenohypophysis, with and without the pars tuberalis were
      cultured in the presence and absence of 10 nM melatonin to determine whether the
      pars tuberalis mediates the previously observed suppressive effects of melatonin
      on the seasonal increase in plasma prolactin levels in this species. Pituitaries
      obtained during long-day photoperiods secreted significantly more prolactin than
      those obtained during the short-day photoperiod. Melatonin had no effect on
      pituitary response to gonadotropin releasing hormone and failed to inhibit
      prolactin secretion during the 48 h culture period. However, melatonin
      significantly reduced the inhibitory effects of dopamine on prolactin secretion.
      The latter response was observed in both photoperiods and in the presence and
      absence of the pars tuberalis. These results suggest that the pars tuberalis does
      not mediate the inhibitory effect of melatonin on prolactin secretion in the
      absence of the hypothalamus.

PMID- 8263467
TI  - Development of collared lemmings, Dicrostonyx groenlandicus, is influenced by pre
      and postweaning photoperiods.
AB  - We examined the role of pre- and postweaning photoperiod on postweaning
      development of collared lemmings. Lemmings were gestated and reared to weaning
      (19 days of age) in one of three photoperiods: 22L:2D (22 hr of light:2 hr of
      dark), 16L:8D, and 8L:16D. At weaning, lemmings were either maintained in their
      natal photoperiod or transferred to one of the other two photoperiods. At the
      termination of the experiment (10 weeks postweaning) data were collected on
      somatic characters (body weight, bifid claw width, pelage stage, and guard hair
      length), serum prolactin (PRL), and reproductive parameters (testes, seminal
      vesicle, and uterine weights). Somatic characters were predominantly influenced
      by postweaning photoperiod, when that photoperiod was either long (22L:2D) or
      short (8L:16D). When lemmings were exposed to an intermediate postweaning
      photoperiod (16L:8D), development of somatic characters was significantly
      influenced by the preweaning photoperiod; animals reared in 8L:16D regarded
      16L:8D as a long day, whereas those reared in 22L:2D regarded 16L:8D as a short
      day. Serum PRL responded to photoperiod changes, often reflecting either the
      increase or decrease in day length, rather than simply the absolute number of
      light hours per day. Whereas reproductive indices in both sexes were stimulated
      by transfer from short to long photoperiod, chronic exposure to long photoperiod
      inhibited male development. No other photoperiod manipulations significantly
      influenced reproductive parameters. These observations suggest that, in the
      collared lemming, the neural and/or humoral factors regulating somatic and
      reproductive characters differ in their response to photoperiod. These results
      also suggest that the postweaning responses to photoperiod are programmed by
      earlier (gestational and/or neonatal) photoperiod exposure of the mother and/or
      the neonates.

PMID- 8263468
TI  - Acquisition of maturational competence in in vitro grown mouse oocytes.
AB  - The maturational competence of the in vitro grown mouse oocytes of various sizes
      was examined, and was compared to that of oocytes of equivalent chronological age
      which grew in vivo. Oocyte-granulosa cell complexes isolated from 10-day-old
      female mice were cultured for 10 days in vitro in the presence of 2 mM
      hypoxanthine to maintain the meiotic arrest. When the in vitro grown oocytes were
      denuded and cultured for further 24 h in the hypoxanthine-free medium, 9, 37, and
      100% of oocytes of 60-64.5, 65-69.5, and over 70 microns in diameter underwent
      germinal vesicle breakdown (GVBD), respectively. Of those oocytes which underwent
      GVBD, 19, 37 and 68% of oocytes larger than 60, 65, and 70 microns progressed to
      metaphase II, respectively. No oocyte less than 60 microns resumed meiosis. The
      parallelism found in the oocyte size and maturational competence was similar to
      that of their in vivo counterparts collected from 20-day-old mice. A significant
      proportion of the in vitro grown oocytes, however, formed a pronucleus-like
      structure(s) after maturation culture, indicating that they could not maintain a
      normal arrest at metaphase II.

PMID- 8263469
TI  - A discussion of "Ultraviolet radiation and its role in wound pattern
      documentation".

PMID- 8263470
TI  - A discussion of "The detection and documentation of trace wound patterns by use
      of an alternative light source".

PMID- 8263471
TI  - A discussion of "Deaths caused by lightning".

PMID- 8263472
TI  - A concern associated with single breath alcohol analysis for forensic purposes.

PMID- 8263473
TI  - Alcohol in decomposed bodies: postmortem synthesis and distribution.
AB  - Blood alcohol (ethanol) concentrations in decomposed bodies can mean drinking
      during life and/or endogenous production after death. The correct interpretation
      is important in medicolegal cases. This retrospective study of 286 autopsied
      medical examiner cases was undertaken to evaluate alcohol concentrations and
      distribution in various fluids and tissues in decomposed bodies. Cases with
      alcohol present were classified as endogenous production, ingestion, or unable to
      determine based upon one or more of the following criteria: the presence of
      ethanol in only one of more than one body fluids, an atypical distribution of
      ethanol in body fluids, reliable scene or historical information, the presence of
      C3 alcohols in body fluids. Alcohol was classified as endogenously produced in 55
      cases. The presence of alcohol was attributed to ingestion in 130 cases. No
      alcohol was detected in 39 cases. We were unable to determine the source of the
      remaining 62 alcohol concentrations. The highest blood alcohol concentration
      derived from endogenous production was 0.07% in the cases with other fluids
      negative. The mean blood alcohol concentration was 0.06% and ranged as high as
      0.16% in cases having atypical ratios. Alcohol was found in blood and bile while
      urine and vitreous fluid were negative or had lower concentrations in cases with
      endogenous production. We conclude that for the majority of cases in which
      endogenous blood production of alcohol occurs the concentration in blood may be
      as high as 0.15%.

PMID- 8263474
TI  - Simultaneous analysis of codeine, morphine, and heroin after B-glucuronidase
      hydrolysis.
AB  - Analysis of the opiates, morphine and codeine, often proceeds by way of acid
      hydrolysis for release of the parent morphine from its glucuronide formed during
      metabolism. Following use, heroin is rapidly deacetylated to 6-monoacetylmorphine
      (6-MAM), which can be detected in the urine for a short time following injection
      of heroin. Only a small amount of 6-MAM may be further metabolized to morphine
      glucuronide. Thus, in general, the urine specimen has not been hydrolyzed prior
      to analysis for heroin, using a separate procedure from morphine and codeine.
      Simultaneous analysis of morphine, codeine, 6-MAM and heroin would be complicated
      by loss of identity between morphine and heroin when heroin converts to morphine
      following acid hydrolysis for removal of the glucuronide moiety from morphine
      glucuronide. Another significant problem in simultaneous analysis is the relative
      disparity in concentration between morphine/codeine and 6-MAM/heroin (which might
      be present in the urine specimen). In the proposed method of analysis, free
      morphine resulting from B-glucuronidase rather than acid hydrolysis of morphine
      glucuronide is derivatized with propionic anhydride to form dipropionylmorphine.
      Heroin that does not react with B-glucuronidase remains unhydrolyzed as the
      diacetylmorphine derivative. Some of the more exacting steps for the acid
      procedure are eliminated altogether making overall costs for the enzyme procedure
      comparable to those of the acid hydrolysis method. The enzyme reaction mixture is
      purified through a solid phase column system. The optimal conditions for
      concentration of enzyme, temperature of hydrolysis and pH are individually
      characterized for B-glucuronidase hydrolysis and the ions which identify the
      propionyl derivatives are characterized for the simultaneous analysis of
      morphine, codeine, 6-MAM and heroin.

PMID- 8263475
TI  - The application of capillary gas chromatography-electron capture detection in the
      comparative analyses of illicit cocaine samples.
AB  - The gas chromatographic detection of manufacturing impurities in illicit cocaine
      can be enhanced by chemical derivatization and the use of an electron-capture
      detector. After derivatization of illicit cocaine hydrochloride samples with
      heptafluorobutyric anhydride, the isolated heptafluorobutyryl derivatives of the
      cocaine impurities were subjected to capillary gas chromatography-electron
      capture detection analysis. The on-column detection of cocaine impurities at low
      picogram levels was possible for compounds such as N-norcocaine and other N
      demethylated impurities, amidic by-products, including N-benzoylnorecgonine
      methyl ester and tertiary amines possessing hydroxy functions. The latter
      compounds include the so-called hydroxycocaine impurities, believed to be new
      coca leaf alkaloids. This methodology is especially suited for sample comparison
      analyses.

PMID- 8263476
TI  - The anatomy of a cocaine comparison case: a prosecutorial and chemistry
      perspective.
AB  - Methodology used for the comparative chemical analyses of two illicit cocaine
      seizures, and its application in a successful criminal prosecution, is described.
      A description of events leading to the arrest of the defendant and an overview of
      the jury trial are provided. Illicit cocaine, found in the defendant's suitcase
      and wallet, was subjected to chemical derivatization and three distinct gas
      chromatographic methods for the detection and relative quantitation of cocaine
      manufacturing impurities/by-products. The cocaine impurities included cis- and
      trans-cinnamoylcocaine, the isomeric truxillines and the hydroxycocaines. Among
      the cocaine manufacturing byproducts detected were benzoylecgonine, ecgonine
      methyl ester, ecgonine, N-benzoylnorecgonine methyl ester and N-norcocaine.
      Chemical derivatization of the cocaine samples was accomplished using
      heptafluorobutyric anhydride and N,O-bis(trimethylsilyl)acetamide. The
      derivatized impurities/by-products were subjected to capillary gas
      chromatographic analysis using both flame ionization and electron-capture
      detectors. The comparative chemical analyses provided a positive correlation
      between the suitcase and wallet cocaine samples.

PMID- 8263477
TI  - Method comparison of EMIT II and online with RIA for drug screening.
AB  - The newest formulation of the EMIT assay for drugs of abuse, EMIT II, and a new
      immunoassay, OnLine, using the kinetic interaction of microparticles in solution
      methodology, were evaluated for marijuana, cocaine, opiates, barbiturates, and
      phencyclidine. Both types of immunoassays were performed on an Hitachi 717
      analyzer. Calibration curves, the degree of separation between negative and
      cutoff calibrators, precision, probability of carryover from positive to negative
      samples, and overall ease and speed of analysis were evaluated. EMIT II and
      OnLine were compared with RIA tests for the five drugs to determine each assay's
      ability to detect samples which confirm positive by GC/MS. The RIA and OnLine
      marijuana tests detected > 99% of confirmed positive samples while EMIT II
      detected about 90%. All three immunoassays performed equivalently for cocaine and
      opiates, each assay detecting at least 98% of positives. Barbiturates showed the
      greatest disparity with OnLine detecting 96%, EMIT II 85%, and RIA 79% of
      confirmed positive samples. Too few phencyclidine positive samples were detected
      for a method comparison study. The fully automated EMIT II and OnLine assays are
      preferable for a variety of reasons to our laboratory's current semi-automated
      RIA tests for large volume urine testing. The immunoassays offer comparable
      performance for some drugs but not for others.

PMID- 8263478
TI  - The prevalence of drugs and alcohol in fatally injured truck drivers.
AB  - To assess the impact of alcohol and other drug use in the trucking industry, the
      National Transportation Safety Board, in collaboration with The National
      Institute on Drug Abuse investigated fatal-to-the-driver trucking accidents in
      eight states over a one year period. Comprehensive drug screens were performed on
      blood specimens collected from 168 fatally injured drivers. One or more drugs
      were detected in 67% of the drivers and 33% of the drivers had detectable blood
      concentrations of psychoactive drugs or alcohol. The most prevalent drugs were
      cannabinoids and ethanol, each found in 13% of the drivers. Cocaine or
      benzoylecgonine was found in 8% of the cases. Seven percent of the driver's blood
      specimens contained amphetamine or methamphetamine and 7% contained
      phenylpropanolamine, ephedrine, or pseudoephedrine. A panel of toxicologists
      reviewed the accident investigation report and the toxicology findings for each
      case and determined that impairment due to marijuana use was a factor in all
      cases where the delta-9-tetrahydrocannabinol concentration exceeded 1.0 ng/mL and
      that alcohol impairment contributed to all accidents where the blood alcohol
      concentration was 0.04% wt/vol or greater. In 50 of 56 cases where psychoactive
      drugs or alcohol were found, impairment due to substance use contributed to the
      fatal accident.

PMID- 8263479
TI  - International trade in bear gall bladders: forensic source inference.
AB  - Fresh and desiccated gall bladders of the Ursidae family (bears) obtained as
      criminal evidence were characterized by analysis of the principal biliary
      components, mainly ursodeoxycholyl-taurine, cholyl-taurine and chenodeoxycholyl
      taurine using TLC and HPLC. This bile acids profile appears to be an Ursidae
      family characteristic. Results show that of the samples from Asia only 3% were
      from the Ursidae family and 18% were from "farmed bears." Samples seized in the
      U.S.A. and Canada showed that 22.6% and 85% respectively, were from Ursids. The
      remaining samples were consistent with bile from the domestic pig (Suidae).

PMID- 8263480
TI  - Identification of the fragmentary, burned remains of two U.S. journalists seven
      years after their disappearance in Guatemala.
AB  - The contribution of a physical anthropologist to a forensic investigation is
      generally associated with analysis of skeletal remains in a laboratory. This
      case, which deals with the identification of two U.S. journalists who disappeared
      in Guatemala in March 1985, shows that the observations of a physical
      anthropologist in the field--at the site where the skeletal remains are located-
      can be essential to the success of an investigation. In this case, there was a
      deliberate attempt to mislead the investigators, but the physical anthropologists
      on the team discovered the deception. Subsequently, when they were taken to the
      actual cremation site, they obtained bone fragments and teeth that permitted
      identification of the victims. For one individual, the unusual morphology of the
      frontal sinus made positive identification possible. Comparison of premortem
      dental X-rays with teeth found at the site resulted in positive identification of
      the second individual.

PMID- 8263481
TI  - Variation in birth timing and location of the neonatal line in human enamel.
AB  - The location of the neonatal line in 173 primary teeth from 43 children was
      investigated and shown to differ significantly among pre-term, term, and post
      term births. Approximately 75% of the neonatal lines that lie beyond 2SD of the
      mean location of the line in term births are from children born outside of 38 to
      42 weeks gestation. The duration of pregnancy accounts for about 36% of the
      variation in location of the neonatal line in non-term births. Based on the small
      proportion of non-term births whose neonatal line is located beyond 2SD of the
      mean location of the neonatal line in term births, it is estimated that this
      technique will provide individualizing information in about 3% of immature
      skeletonized remains in a forensic context. The relative timing of pre- and
      postnatal pathological striae in the enamel of primary teeth can be evaluated in
      terms of the variation, documented here, in the location of the neonatal line due
      to individual and birth timing differences. Determination of the timing of
      pathological enamel striae will aid in the identification of both children and
      adults for whom histological examination of enamel is undertaken.

PMID- 8263482
TI  - The Iceman murder: one of a series of contract murders.
AB  - A body with a gunshot wound to the head was discovered in a wooded area in mid
      September 1983 wrapped with about 20 consecutive layers of plastic garbage bags
      and rope. Examination of the body revealed a bullet hole in the occipital
      parietal region and a peculiar decomposition of the body. Following a forensic
      reconstruction of our autopsy findings, microscopic studies and other ancillary
      factors, we concluded that the body had been frozen for about 2 and one-quarter
      years prior to its being dumped along a mountain road here in Rockland County.
      The means by which we concluded that the victim had been frozen for about 2 and
      one-quarter years and other important aspects of this case are fully discussed.

PMID- 8263483
TI  - Gunshot fatalities in Stockholm, Sweden with special reference to the use of
      illegal weapons.
AB  - During the years 1980-1992 the Swedish legislation regarding possession and use
      of firearms has remained fairly unchanged. Simultaneously the reported incidence
      of both stolen firearms and confiscation of illegally possessed handguns has
      increased significantly. In order to determine the impact of this trend on
      gunshot mortality, all victims of firearm fatalities subjected to medicolegal
      autopsy in the Stockholm area 1980-81 and 1990-91 were studied. The overall two
      year rate increased from 50 to 65, homicides and suicides contributing seven new
      cases each; accidents and "not determined" comprising only 0 to 2 cases in each
      period. Suicides were four times as common as homicides in the former period; ca.
      three times as common in the latter. Thus, a 70% increase in homicidal shooting
      has occurred (from 10 to 17), and the fatal use of illegal firearms increased
      from 50% to 93%. As expected, there was a definite male dominance (96%) among
      perpetrators as well as among victims (85%). Concerning suicides, the rate in the
      latter period was 18% above that in the former; illegal guns were used in 30% in
      1990-91 as compared to 20% 1980-81. The pattern of wounding in suicides was
      similar to that reported in earlier studies; confirming that entrance wounds in
      the back, extremities and lower abdomen are indicative of homicide. Thus, common
      sense knowledge of firearm fatalities are confirmed: More widespread access to
      illegal weapons conveys a higher rate of gunshot fatalities. The perpetrator is
      likely to be male. Suicidal shots are usually aimed at the head (mouth, temple,
      forehead) or precordium. Most gunshot suicides are committed by means of legally
      possessed firearms.

PMID- 8263484
TI  - Suicidal drowning.
AB  - Autopsy protocols at the office of the Chief Forensic Pathologist were reviewed
      with respect to suicidal drowning. Within the years 1987 to 1991, 247 people have
      committed suicide in the Province of Newfoundland. Of that number, 22 committed
      suicide by drowning, representing 8.9% of all suicides, and the fourth leading
      cause of suicidal death. When considering suicide in the age group of 50 years
      and older, (n = 68), which accounts for 27.5% of all suicides, drowning
      represents 25% of all suicidal deaths, and within females in this group
      represents the most common form of suicidal death (45.5%). The presence of
      alcohol or other drugs is decidedly unusual in such victims. Of the 22 drowning
      suicides, 19 were committed in the ocean, two were committed in fresh water and
      one committed in a residential well. These results contrast to similar studies
      performed in locations in which access to water could be reasonably considered a
      factor in choosing a method of suicide.

PMID- 8263485
TI  - Histiocytoid cardiomyopathy: case report and literature review.
AB  - The sudden death of an infant may be due to a variety of causes. In such cases,
      complete autopsy with radiologic, gross, microscopic, and toxicologic examination
      is warranted. We present a case of a previously healthy 15-month-old girl with no
      known disease, who experienced witnessed cardiac arrest, ventricular
      fibrillation, and death. Complete postmortem examination revealed histiocytoid
      cardiomyopathy as the cause of death. Histiocytoid cardiomyopathy is a rare
      infantile cardiac-muscle disorder characterized by the presence of enlarged,
      polygonal subendocardial myocytes which, by light microscopy, lack normal
      striations, and instead have granular, faintly eosinophilic cytoplasm.
      Ultrastructurally, the myocytes contain numerous mitochondria and markedly
      reduced numbers of myofibrils. Clinically, the disorder is characterized by
      cardiac arrhythmias and/or sudden death occurring in children under the age of
      two years. We discuss the differential diagnosis, proposed theories of etiology,
      and the pathology of this rare entity.

PMID- 8263486
TI  - The psychotic patient as security guard.
AB  - The job of the security guard is generally regarded as stressful because of the
      potential for violent or other hostile confrontation. Although the public assumes
      that only mentally healthy individuals who possess the capability to handle
      stressful situations become employed as security guards, this may not be the
      case. A series of 15 individuals who suffered from psychotic disorders while
      working as security guards is studied and discussed in terms of the issues of
      dangerousness and public safety. One case is described in detail in order to
      highlight important issues resulting from being psychotic while working as a
      security guard.

PMID- 8263487
TI  - Competency, civil commitment, and the dangerousness of the mentally ill.
AB  - The purpose of this study was to assess if a relationship exists between the
      nature of an individuals criminal charges and the finding of fitness among
      defendants evaluated at the Forensic Psychiatry Clinic servicing Manhattan. We
      examined the records of 354 defendants referred to the Forensic Clinic from the
      New York Criminal and Supreme Courts for a competency to stand trial evaluation.
      We reviewed their charges in light of the finding of competency. Incompetent
      defendants were most often accused of misdemeanors rather than felonies and of
      non-violent rather than violent crimes. Perhaps individuals who are thought to be
      psychiatrically disturbed get detained by the police on trivial charges so as to
      get them off the streets. Deinstitutionalization and civil commitment laws are
      considered as contributing factors and their impact is discussed.

PMID- 8263488
TI  - Production of urinary ethanol after sample collection.
AB  - As the interest in urine drug testing grows, ethanol is frequently included in
      drug-abuse screening. Collection of urine for drug testing is less invasive than
      blood collection and is used to screen employees in a large cross-section of
      occupations. Because alcohol can be produced from carbohydrates via fermentation,
      our interest was to determine: (1) if ethanol could be produced in glucose
      positive urine (2) under what microbiological conditions would this process
      occur, and (3) would the urine ethanol concentration be significant. Fourteen
      urine specimens were selected from the Urinalysis Laboratory of a large medical
      center. All specimens were tested for ethanol concentration on the day of voiding
      and were found to be negative (< 0.01 mg/100 mL). Urine glucose concentrations
      ranged from 0 to > or = 2000 mg/dL. Microbiological examinations were performed
      on all specimens. Storing the samples at room temperature, five of the specimens
      produced ethanol over the time course of the study (1 to 21 days) in
      concentrations ranging from 0.036 to 2.327 g/100 mL. Yeast was identified in the
      five glucose positive urine samples producing ethanol. Six glucose positive urine
      samples that did not produce ethanol were found to be yeast negative. Findings
      indicate that significant ethanol concentrations can develop from glucose and
      yeast positive urine, after the day of voiding.

PMID- 8263489
TI  - Computer aided retrieval of common-batch members in Leuckart amphetamine
      profiling.
AB  - Comparison of profiles is a well established way to find links between
      confiscated drugs. It is a laborious and time consuming task to manually compare
      large numbers of profiles to find common-batch links. To facilitate the
      comparison a computerized method has been developed. It is described and applied
      to a set of amphetamine impurity profiles. From each profile, areas of selected
      peaks are fed to the computer. By using quotients of corresponding peaks, the
      computer finds pairs of closely related profiles. With a sufficient numbers of
      peaks, the method is tolerant to variations in intensity between profiles, random
      peak area variations and a few strongly deviating peak areas. The program was
      written in Q-basic from Microsoft and may be run on any IBM-compatible personal
      computer. The method may also be used for analyzing data from other forensic
      objects, when the descriptors chosen are affected by errors like those described
      in the text.

PMID- 8263490
TI  - Evaluation of HLA in detection of non-parentage among known false trios.
AB  - This paternity study was performed with trios in which the putative father was
      not the biological father (NBF), in order to evaluate the effectiveness of HLA-A
      and -B phenotyping for routine testing. All 372 generated trios had ABO, Rh, MNS,
      Kell, Duffy, Kidd and HLA (A and B) systems tested. HLA-A and -B phenotyping
      directly excluded 81.73% of NBF. Red blood cell markers excluded 8.82% of NBF
      missed by HLA; only 0.81% of NBF were not identified by the markers used. Each
      laboratory engaged in disputed paternity testing should evaluate its actual
      performance in detecting non-biological fathers and its exclusion rates in real
      trios. These data together can be used as a guide of mother's reliability.

PMID- 8263491
TI  - Paternity investigation among known false trios: ABO, Rh, MNSs, Kell, Duffy,
      Kidd, and HLA systems.
AB  - This paternity study was performed with trios in which the putative father was
      not the biological father (NBF), in order to evaluate adjustment of genetic
      markers employed to disclose non biological fathers for the population, and the
      biological meaning of likelihood of paternity in casework. All 923 generated
      trios had ABO, Rh, MNS, Kell and HLA systems tested; 372 of them also had Duffy
      and Kidd systems tested. The most powerful exclusion system was HLA, followed, in
      this order, by ABO, Rh, Duffy, MNSs, Kidd, and Kell. Taking into account the
      Indian/black/white historical miscegenation background in the population, an
      improvement in the performance of red blood cells as disclosers of non biological
      fathers could be achieved, if particular additional sera were used. In the group
      tested with seven different systems, direct exclusions were observed in 90.31%,
      and they were single system exclusions in 26.61%. In order to avoid the remote
      possibility of mutation, it is suggested that the number of used systems be
      increased. Indirect exclusions were verified in 8.87% and only 0.81% of NBF were
      not excluded at all. In this last group, probabilities of paternity were
      calculated and two values greater than 95% were obtained. To be able to
      accomplish the "visum et repertum" duty and to assist the court, the expert
      should equally emphasize: a) the probability of paternity of the alleged father
      and the possibility of finding an unexcluded NBF; b) the actual performance of
      systems used to uncover NBF, together with the probabilities of paternity of
      those who were not discovered; c) the previous referenced trend of probabilities
      of paternity of true and of non-biological fathers to cluster in distinct class
      intervals of likelihood of paternity.

PMID- 8263492
TI  - Simultaneous subtyping of group specific component and esterase D by isoelectric
      focusing on agarose gels.
AB  - A quick, sensitive and economical technique has been developed to subtype GC and
      ESD simultaneously on the same agarose IEF gel. This method could be a useful
      tool for forensic application.

PMID- 8263493
TI  - Direct sequencing of the human protamine P1 gene and application in forensic
      medicine.
AB  - Protamines are among the most variable nuclear proteins known in eukaryotes. In
      order to learn more about their evolution and function in humans and to explore
      the possibility of potential applications in forensic medicine we have developed
      a rapid method to amplify and directly sequence the protamine P1 gene
      simultaneously in many different samples. The method takes only 3.5 h from
      genomic DNA to the sequencing reactions. Despite the high variability of these
      genes only one polymorphic site was detected at the coding region level in
      different individuals. This polymorphic variation does not create a change in the
      amino-acid sequence of the protamine. Because all the protamine genes sequenced
      from different species are markedly different among them as well as to the human
      sequence, amplification and direct sequencing of this gene can be used to
      unequivocally identify the human or animal origin of biological specimens.
      Furthermore, the single polymorphic site detected in the human P1 gene could be
      useful in conjunction with other markers in identification studies in humans.

PMID- 8263494
TI  - A modified reagent for the confirmation of blood.
AB  - Oxygen and pyridine compete for the same binding site on the heme molecule.
      Lowering the oxygen concentration in Takayama's reagent by addition of an oxygen
      scavenger such as dithiothreitol (Cleland's reagent) shifts this equilibrium in
      favor of pyridine, and increases the rate at which hemochromogen crystals are
      formed. This modification makes the confirmatory test for blood faster, and
      therefore easier to use. The absolute sensitivity and the specificity of the
      reagent appear unchanged.

PMID- 8263495
TI  - Cyanoacrylate adhesive technique in wound edge approximation.
AB  - Cyanoacrylate, the adhesive component of many commercially available strong
      binding glues, has been used by the medical profession for various purposes,
      including tissue adhesion and repair, embolization, sclerotherapy, and
      hemostasis. Mortuary science professionals rely on cyanoacrylate's adhesive
      property to aid in body restoration techniques following embalming. Forensic
      applications include the use of cyanoacrylate fumes for latent fingerprint
      detection. An additional application for this sticky chemical is currently
      unrecognized by many within the forensic community. Specifically, cyanoacrylate's
      adhesive property makes possible the relatively simple, efficient, and rapid
      approximation of disrupted skin and tissue when warranted during a forensic
      autopsy. The final result is aesthetically pleasing and lends itself to
      subsequent photographic documentation especially when patterned injuries are
      encountered. We discuss the technique, benefits, and limitations of the
      cyanoacrylate adhesive method in this setting and present several cases wherein
      the technique has produced satisfying results.

PMID- 8263496
TI  - An accidental death related to cocaine, cocaethylene, and caffeine.
AB  - Cocaethylene is often found in body fluids after concurrent use of alcohol and
      cocaine. Current research is showing that cocaethylene is more toxic than
      cocaine. The case presented here involves a death that is due to cocaine,
      cocaethylene, and caffeine. The cocaethylene concentrations found were 0.16 mg/L
      (blood) and 1.85 mg/L (gastric). Caffeine concentrations were 16.40 mg/L (blood)
      and 15.40 mg/L (gastric). Cocaine was found only in the gastric sample at a level
      of 0.45 mg/L. The blood alcohol of the subject was 10 mg/dL. From the case
      investigation it was determined that the death was accidental but related to the
      ingestion of cocaine and caffeine tablets. With the combination of alcohol and
      cocaine use rising, it is becoming evident that the routine screening of medical
      examiner cases for cocaethylene should be performed.

PMID- 8263497
TI  - Efficacy of a recombinant Norwalk virus protein enzyme immunoassay for the
      diagnosis of infections with Norwalk virus and other human "candidate"
      caliciviruses.
AB  - A recombinant Norwalk virus antigen enzyme immunoassay (rNV EIA) for the
      detection fo Norwalk virus (NV) antibodies was evaluated using sera from
      volunteers and patients infected with Norwalk, Hawaii, Snow Mountain Agent, small
      round structured viruses (SRSV), and human calicivirus (HuCV) strains. The
      results for NV antibodies correlated well with previous results obtained using a
      NV radioimmunoassay. The test rNV EIA was found to be highly specific for NV. The
      results of tests on sera obtained from patients involved in confirmed outbreaks
      of SRSV in the UK showed that only 1/12 was due to Norwalk virus. Further
      evidence is presented that SRSV strain UK2 is antigenically related to NV.

PMID- 8263498
TI  - Cervical HPV infection among HIV-infected prostitutes addicted to hard drugs.
AB  - An investigation into the prevalence of human papilloma virus (HPV) infection,
      abnormal cervical cytology and the relationship between HIV- and HPV infection
      was done in a group of intravenously (IV) and non-IV drug-using prostitutes. From
      July 1991 through May 1992, hard drug-addicted prostitutes attending a sexually
      transmitted-disease (STD) clinic in Amsterdam were recruited. A questionnaire was
      administered to obtain demographic characteristics, and medical and STD history.
      Apart from routine STD examination, cervical scrapes for cytology and samples for
      HPV DNA detection by polymerase chain reaction (PCR) were collected. Some of the
      women included in this study also participated in HIV studies among drug users.
      Their data on HIV- and immunologic status could be combined. A total of 121 women
      entered the study; 25 women were HIV-seropositive, 44 women were HIV-negative,
      and the HIV status of 52 women was unknown. All 25 HIV-positive women had normal
      Pap smears, two of the 44 HIV-negative women had a Pap smear III A, and in the
      HIV-unknown group, two women with Pap III A and one with Pap III B were found.
      Eight of the 25 (32%) HIV-positive women were HPV DNA-positive, three of the 44
      (7%) HIV-negative women and 10/52 (19%) of the HIV-unknown group. Logistic
      regression analysis showed that in the total group, presence or cervical HPV DNA
      was associated with HIV infection (order ratio [OR] for HIV-positives 7.8, 95%
      confidence interval [CI] 1.8 to 34.6) and with diagnosis of condylomata acuminata
      at entry to the study (OR 7.5, 95% CI 1.5 to 36.5).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263499
TI  - Activity of the Keggin polyoxotungstate PM-19 against herpes simplex virus type 2
      infection in immunosuppressed mice: role of peritoneal macrophage activation.
AB  - The in vivo antiviral activity of the Keggin polyoxotungstate PM-19
      [K7(PTi2W10O40).6H2O] against herpes simplex virus type 2 (HSV-2) was
      investigated in mice immunosuppressed by cyclophosphamide (CY). When PM-19 was
      administered intraperitoneally to immunosuppressed mice for 3 days (once daily)
      starting at the time of infection, it prevented death due to HSV-2 encephalitis
      in a dose-dependent manner (10-25 mg/kg). The in vivo anti-HSV-2 activity of PM
      19 was superior to that of acyclovir. Intraperitoneal administration of PM-19 to
      the immunosuppressed mice significantly increased the number of peritoneal cells,
      especially macrophages. PM-19 did not stimulate interferon-inducing activity or
      natural killer cell activity, but markedly enhanced peritoneal macrophage
      functions: (1) phagocytic activity as assessed by measuring the amount of 51Cr
      labeled sheep red blood cells taken into the macrophages, and (2) extrinsic
      antiviral activity as monitored by reduction in the numbers of plaque formed upon
      cocultivation of HSV-2-infected HEL cells with the macrophages. These results
      point to the role of peritoneal macrophage activation in the activity of PM-19
      against HSV-2 infection in immunosuppressed mice.

PMID- 8263500
TI  - Slow maturation of IgG1 avidity and persistence of specific IgM in congenital
      rubella: implications for diagnosis and immunopathology.
AB  - Without appropriately timed specimens, serological confirmation of congenital
      rubella infection may be a problem. We have compared the persistence of specific
      IgM and low avidity specific IgG1 in 141 sera from 120 cases of serologically
      confirmed congenital rubella infection with the known time scales for postnatal
      primary rubella. The results demonstrate that the maturation of the immune
      response to the rubella virus is abnormally slow in congenital rubella cases both
      in terms of the isotype switch and especially the development of high avidity
      specific IgG1. Thus avidity studies may permit serological confirmation of
      congenital rubella for longer than is possible with tests currently in use. The
      pathological implications of prolonged low avidity antibody production are
      discussed.

PMID- 8263501
TI  - Sensitive assays for hepatitis A antibodies.
AB  - Two commercial assay kits for detecting antibody to hepatitis A virus (anti-HAV)
      have been modified in order to increase their sensitivity. These modifications
      are made by less dilution of the test serum, in the case of Abbott HAVAB-M assay,
      or by an increase in the volumetric ratio of the test serum to the labeled anti
      HAV in the case of the Abbott HAVAB assay. These modifications result in 5- to 20
      fold increases in test sensitivity and enable the detection of anti-HAV at 2-3
      weeks following vaccination. The earlier detection of anti-HAV is important to
      vaccine development in assuring the presence of antibody levels in travelers
      sooner after vaccination.

PMID- 8263502
TI  - Serologic markers of viral hepatitis A, B, C, and D in patients with hemophilia.
AB  - Forty-one patients with hemophilia A were studied for the prevalence of
      serological markers for hepatitis A, hepatitis B, hepatitis C (non-A and non-B
      hepatitis), and delta hepatitis (hepatitis D). Ten of 41 (24.4%) patients
      demonstrated hepatitis A antibody and 31 of 41 (75.6%) patients had a serologic
      marker for previous hepatitis B infection; four of these 31 patients (13%) also
      demonstrated antibody to delta agent (hepatitis D). Thirty-seven of 41 (90.2%)
      patients demonstrated antibody for hepatitis C. Nine of 31 (29%) patients with a
      hepatitis B marker (no hepatitis B vaccinees) were negative for anti-HBc but
      positive for anti-HBs; all of these nine patients were HIV antibody positive,
      although they had no overt immunodeficiency. Twenty-six of 41 (63.5%) patients
      were HIV antibody positive. Of HIV antibody positive patients, 27%, 88%, and 100%
      demonstrated evidence of a previous hepatitis A, hepatitis B, or hepatitis C,
      respectively. Of HIV antibody negative patients; 20%, 53%, and 73% of the
      patients demonstrated evidence of a previous hepatitis A, hepatitis B, or
      hepatitis C infections, respectively. The difference between HIV antibody
      positive and HIV antibody negative groups was not significant for hepatitis A but
      was significant for hepatitis B (P < 0.001) and hepatitis C (P < .001). Of the 31
      patients with a hepatitis B serologic marker, all had antibody to hepatitis C. Of
      10 patients, without a hepatitis B serologic marker, only 6 (60%) had antibody to
      hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263503
TI  - Partial control of hepatitis delta virus superinfection by immunisation of
      woodchucks (Marmota monax) with hepatitis delta antigen expressed by a
      recombinant vaccinia or baculovirus.
AB  - We have successfully limited the level of hepatitis delta viraemia occurring
      after superinfection of hepadna-virus infected woodchucks by prior immunisation
      with the short form of the hepatitis delta virus antigen expressed by a
      recombinant baculovirus or vaccinia virus. This phenomenon occurred in the
      absence of detectable circulating antibody to hepatitis delta virus antigen and
      in the absence of evidence of priming of the humoral immune response and may
      reflect the induction of a cytotoxic T-cell response. The latter would control
      viraemia by rapid lysis of delta antigen expressing hepatocytes. It is suggested
      that the T-cell epitopes involved may be located on the carboxyl end of the delta
      protein (amino acids 77-195).

PMID- 8263504
TI  - Partial sequence comparison of eight new Chinese strains of hepatitis E virus
      suggests the genome sequence is relatively stable.
AB  - Partial genomic sequences representing 420 nucleotides of a nonstructional
      region, 480 nucleotides of the putative RNA polymerase region, and 540
      nucleotides of the structural region of epidemic-associated Chinese strains of
      hepatitis E virus (HEV) were obtained by direct sequencing of PCR-amplified DNA.
      Comparison with previously published HEV sequences showed a clear relatedness of
      all Chinese strains to each other and to a Pakistani strain (Sar-55). All eight
      Chinese strains examined had very similar sequences (98.5-99.8% homology) in the
      regions examined and were much closer to the Pakistani strain (Sar-55) (97.9
      98.4% homology) than to the Burmese strain (92.5-93.3% homology). Sequence
      comparisons of the three genomic regions in the Chinese strains indicated that
      the RNA polymerase region was much more conserved than the other nonstructural
      region or the structural region. HEV isolates from three remote geographic
      regions of China had sequences closely related to each other.

PMID- 8263505
TI  - Efficacy of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine for the treatment
      of lethal vaccinia virus infections in severe combined immune deficiency (SCID)
      mice.
AB  - Severe combined immune deficient (SCID) mice inoculated intravenously with
      vaccinia virus (VV) became sick within 6-8 days and died 10-12 days after
      infection. Tail lesions developed and the number depended on the virus inoculum.
      Age-matched immunocompetent NMRI mice similarly infected also developed tail
      lesions but did not become sick. When the infected SCID mice were treated with
      the acyclic nucleoside phosphonate HPMPC [(S)-1-(3-hydroxy-2
      phosphonylmethoxypropyl)cytosine], either for 5 consecutive days starting on the
      day of infection or for 5 consecutive days starting on day 2, 4, or 6 post
      infection, or as a single dose at 7 days or 1 day before infection, VV-associated
      death was significantly delayed. VV-infected SCID mice that received two doses of
      20 mg/kg of HPMPC every week survived the infection for about 130 days. The
      period during which the mice remained disease-free following HPMPC treatment
      correlated with the absence of detectable virus in their organs. The VV/SCID
      mouse model employed here may be useful for determining whether (attenuated)
      recombinant VV (carrying HIV genes) may have detrimental effects in the
      immunodeficient host. HPMPC may be considered as a drug candidate for the
      treatment and prophylaxis of such complications.

PMID- 8263506
TI  - Small round virus excretion in long-stay geriatric patients.
AB  - The role of small round viruses (SRVs) in gastroenteritis has not been evaluated.
      We undertook a study to evaluate SRV excretion in 40 elderly patients over 12
      months in long-stay, geriatric wards. The 40 patients (11 male, 29 female) had an
      age range of 73-99 years. Samples were received monthly as long as the patients
      were alive. Samples were available from 30 patients (75%) for 6 months or more,
      and 20 (50%) patients completed the study. Ten grams of faeces were collected and
      prepared as 10-20% suspensions, and then concentrated and examined by electron
      microscopy. Of 348 samples examined, 116 (33%) contained SRVs. Only 5 of 40
      patients did not excrete virus. However, in 103/116 (89%) positive samples, virus
      was present in small amounts. These results show that excretion of SRVs in
      asymptomatic patients was very common. Therefore, the detection of SRVs in small
      amounts during an outbreak of gastroenteritis suggest that they do not have a
      causal role.

PMID- 8263507
TI  - Detection of enteroviruses in endomyocardial biopsy by molecular approach.

PMID- 8263509
TI  - Differential profiles of binding of a radiolabeled agonist and antagonist at a
      glycine recognition domain on the N-methyl-D-aspartate receptor ionophore complex
      in rat brain.
AB  - Addition of several polyamines, including spermidine and spermine, was effective
      in inhibiting binding of the antagonist ligand [3H]5,7-dichlorokynurenic acid
      ([3H]-DCKA) a Gly recognition domain on the N-methyl-D-aspartic acid (NMDA)
      receptor ionophore complex in rat brain synaptic membranes. In contrast, [3H]DCKA
      binding was significantly potentiated by addition of proposed polyamine
      antagonists, such as ifenprodil and (+/-)-alpha-(4-chlorophenyl)-4-[(4
      fluorophenyl) methyl]-1-piperidine ethanol, with [3H]Gly binding being unchanged.
      The inhibition by spermidine was significantly prevented by inclusion of
      ifenprodil. In addition, spermidine significantly attenuated the abilities of
      four different antagonists at the Gly domain to displace [3H]DCKA binding
      virtually without affecting those of four different agonists. Phospholipases A2
      and C and p-chloromercuribenzosulfonic acid were invariably effective in
      significantly inhibiting [3H]DCKA binding with [3H]Gly binding being unaltered.
      Moreover, the densities of [3H]DCKA binding were not significantly different from
      those of [3H]-Gly binding in the hippocampus and cerebral cortex, whereas the
      cerebellum had more than a fourfold higher density of [3H]Gly binding than of
      [3H]DCKA binding. These results suggest that the Gly domain may have at least two
      different forms based on the preference to agonists and antagonists in the rodent
      brain.

PMID- 8263508
TI  - Molecular cloning, expression, and pharmacological characterization of humEAA1, a
      human kainate receptor subunit.
AB  - Kainate is a potent neuroexcitatory agent; its neurotoxicity is thought to be
      mediated by an ionotropic receptor with a nanomolar affinity for kainate. In this
      report, we describe the cloning of a cDNA encoding a human glutamate ionotropic
      receptor subunit protein from a human hippocampal library. This cDNA, termed
      humEAA1, is most closely related to rat and human cDNAs for kainate receptor
      proteins and, when expressed in COS or Chinese hamster ovary cells, is associated
      with high-affinity kainate receptor binding. We have successfully established
      cell lines stably expressing humEAA1. This is the first report of establishment
      of stable cell lines expressing a glutamate receptor subunit. The relative
      potency of compounds for displacing [3H]kainate binding of humEAA1 receptors
      expressed in these stable cell lines was kainate > quisqualate > domoate > L
      glutamate >> (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid >
      dihydrokainate > 6,7-dinitroquinoxaline-2,3-dione > 6-cyano-7-nitroquinoxaline
      2,3-dione. Homooligomeric expression of humEAA1 does not appear to elicit ligand
      gated ion channel activity. Nevertheless, the molecular structure and
      pharmacological characterization of high-affinity kainate binding of the humEAA1
      expressed in the stable cell line (ppEAA1-16) suggest that the humEAA1 is a
      subunit protein of a human kainate receptor complex.

PMID- 8263510
TI  - Spontaneous release of acetylcholine from Torpedo synaptosomes: effect of
      cetiedil and its analogue MR 16728.
AB  - The effects of cetiedil and its analogue MR 16728 were examined on spontaneous
      acetylcholine release measured with a chemiluminescent assay using choline
      oxidase in a synaptosomal suspension obtained from Torpedo marmorata electric
      organ. Evoked acetylcholine release is inhibited by cetiedil, whereas this drug
      enhances spontaneous extracellular Ca(2+)-independent acetylcholine release (up
      to 340%). This effect was examined as a function of cetiedil concentration and
      incubation time. On the other hand, the analogue MR 16728, which enhances A23187
      evoked acetylcholine release, also enhances spontaneous Ca(2+)-independent
      acetylcholine release. Cetiedil and MR 16728 effects on spontaneous acetylcholine
      release were also examined in the presence of Ca2+. Addition of Ca2+ enhanced
      spontaneous acetylcholine release by 75%, and cetiedil and MR 16728 stimulation
      was maintained but with different levels of enhancement. Thus, these results show
      that the processes responsible for evoked and spontaneous acetylcholine release
      are sensitive but in different ways to drugs of the cetiedil family.

PMID- 8263511
TI  - Thyrotropin-releasing hormone release is enhanced in hippocampal slices after
      electroconvulsive shock.
AB  - Hippocampal thyrotropin-releasing hormone (TRH) release was examined after
      seizures were induced by electroconvulsive shock (ECS). Rat hippocampal slices
      taken 12, 24, or 48 h after 3 days of alternate-day ECS treatment or sham-ECS
      treatment were stimulated with potassium with or without calcium in a superfusion
      system containing in-line charcoal adsorbent to concentrate TRH. Released TRH and
      tissue TRH were measured by radioimmunoassay. The TRH content of hippocampal
      slices was increased fivefold over sham-ECS levels 12, 24, and 48 h after ECS,
      but this was not associated with an increase in basal TRH release. Potassium
      stimulated TRH release was significantly elevated over basal release 12, 24, and
      48 h after ECS. Potassium-stimulated calcium-dependent TRH release increased
      linearly after ECS, reaching its highest level 48 h after seizure. Thus, although
      enhanced calcium-dependent TRH release was associated with elevated tissue
      levels, this relationship was not proportional in that tissue TRH was elevated to
      the same extent at all times after ECS, whereas potassium-evoked calcium
      dependent TRH release increased gradually over time after seizure. These results
      suggest that postictal elevations in TRH are associated with an enhanced capacity
      for release that develops as a result of a time-dependent shift of TRH from a
      storage compartment ot a readily releasable pool. The observed elevation in
      stimulated TRH release may be relevant to seizure-induced modulation of TRH
      receptors in vivo.

PMID- 8263512
TI  - Formation, metabolism, and action of hepoxilin A3 in the rat pineal gland.
AB  - The present study was undertaken to investigate the possible formation of
      hepoxilin A3 in the rat pineal gland and to study the potential physiological
      role for this compound in this tissue. Incubation of homogenates of rat pineal
      glands with arachidonic acid (66 microM) led to the appearance of hepoxilin A3
      (HxA3) analyzed as its stable trihydroxy derivative, trioxilin A3 by gas
      chromatography in both the electron impact and negative ion chemical ionization
      modes. Endogenous formation of HxA3 is estimated to be 1.43 +/- 0.66
      ng/micrograms of protein. This amount is not modified when the tissue is boiled
      (2.07 +/- 0.66 ng/micrograms of protein). However, the formation of this compound
      was stimulated to 21.26 +/- 5.82 ng/micrograms of protein when exogenous
      arachidonic acid was added to the homogenate. Addition of the dual
      cyclooxygenase/lipoxygenase inhibitor BW 755C (10 micrograms) resulted in a
      partial blockade of hepoxilin formation. Using [1-14C]HxA3, we demonstrated that
      the pineal gland contained hepoxilin epoxide hydrolase, which hydrolyzed HxA3
      into trioxilin A3. This hydrolysis was inhibited by 1 mumol/L of 3,3,3
      trichloropropene-1,2-oxide. In a separate study, HxA3 in the presence of 3,3,3
      trichloropropene-1,2-oxide to block the hydrolysis of HxA3 decreased the
      production of cyclic AMP in cultured organ rat pineals after stimulation with 5'
      N-ethylcarboxamidoadenosine, an A1/A2 adenosine receptor agonist. This effect is
      stereospecific because the (8S)-enantiomer is more active in decreasing cyclic
      AMP production (-88.7%) than the (8R)-enantiomer. This is the first demonstration
      of the presence, metabolism, and action of HxA3 in the rat pineal gland.

PMID- 8263513
TI  - Increased iron in the substantia nigra compacta of the MPTP-lesioned
      hemiparkinsonian African green monkey: evidence from proton microprobe elemental
      microanalysis.
AB  - The association of free radicals and particularly free iron in the pathogenesis
      of idiopathic Parkinson's disease and MPTP-induced parkinsonism remains
      controversial. Whereas the actual cause of dopamine cell death in the substantia
      nigra compacta (SNc) remains unknown, disturbances in lipid peroxidation and
      subsequent mitochondrial and cell membrane disruption has been demonstrated. In a
      genetically susceptible host, abnormal elimination of oxygen and trace metal free
      radicals may further damage dopamine cells. Using a unilaterally MPTP-treated
      African Green monkey, which showed obvious contralateral hemiparkinsonism, the
      total free iron concentration was measured. Iron, Fe2+ and Fe3+, but not other
      trace elements, was significantly elevated in the SNc compared with the opposite
      unlesioned side, which was similar to separate control animals. Iron content in
      the SNc, periaqueductal gray area, and crus cerebri was 228-270 ppm. Normal
      control SNc was 285 (+/- 59) ppm, whereas iron levels of 532 (+/- 151) ppm were
      found in the MPTP-lesioned SNc. These animals were drug naive and not on long
      term levodopa maintenance. Proton microprobe elemental analysis was matched
      against adjacent immunocytochemically stained tissue slices to ensure the cells
      studied were in the SNc. Iron was found not only in the degenerating dopamine
      cells themselves but also in the surrounding matrix and glial cells. Whether free
      iron that is not bound to neuromelanin is responsible for dopamine cell death as
      suggested by these experiments remains to be proved.

PMID- 8263515
TI  - Concentrations of amino acids in extracellular fluid after opening of the blood
      brain barrier by intracarotid infusion of protamine sulfate.
AB  - This article evaluates the influence of an opening of the blood-brain barrier
      (BBB) on compounds in brain extracellular fluid. The concentrations of amino
      acids and some other primary amines were determined in dialysates sampled from
      the right parietal cortex of rats before and after an intracarotid infusion of
      protamine sulfate. Extravasated plasma proteins were visualized by Evans
      blue/albumin and immunohistochemistry. CSF albumin--an indicator of blood-CSF
      barrier opening--was quantified with immunoelectrophoresis. The brains were
      macroscopically edematous after 10 mg but not after 5 mg of protamine sulfate.
      The higher dose led to a 50% death rate. The concentrations of amino acids did
      not change 10 min after the BBB opening. No significant alterations in the amino
      acid concentrations were observed after the lower dose. The concentrations of
      glutamate, aspartate, GABA, glycine, taurine, and phosphoethanolamine increased
      significantly within 50-80 min after the infusion of 10 mg of protamine sulfate.
      CSF albumin levels were significantly increased 1 h after infusion. We conclude
      that a dysfunction of the BBB, of a degree known to induce brain edema (10 mg of
      protamine sulfate), significantly increases the extracellular concentration of
      excitatory amino acids, GABA, taurine, and phosphoethanolamine in the
      extracellular space.

PMID- 8263514
TI  - Decreased myo-inositol uptake is associated with reduced bradykinin-stimulated
      phosphatidylinositol synthesis and diacylglycerol content in cultured
      neuroblastoma cells exposed to L-fucose.
AB  - L-Fucose is a potent, competitive inhibitor of myo-inositol transport by cultured
      mammalian cells. Chronic exposure of neuroblastoma cells to L-fucose causes a
      concentration-dependent decrease in myo-inositol content, accumulation, and
      incorporation into phosphoinositides. In these studies, L-fucose supplementation
      of culture medium was used to assess the effect of decreased myo-inositol
      metabolism and content on bradykinin-stimulated phosphatidylinositol synthesis
      and diacylglycerol production. Chronic exposure of cells to 30 mM L-fucose caused
      a sustained decrease in bradykinin-stimulated, but not basal, 3H-inositol
      phosphate release and 32P incorporation into phosphatidylinositol in cells
      incubated in serum-free, unsupplemented medium. In addition, 32P incorporation
      into phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate
      was not altered in L-fucose-conditioned cells. Acute exposure of cells to serum
      free medium containing 30 mM L-fucose did not affect either basal or bradykinin
      stimulated 32P incorporation into phosphatidylinositol. Basal diacylglycerol
      content was decreased by 20% in cells chronically exposed to 30 mM L-fucose,
      although analysis of the molecular species profile revealed no compositional
      change. Bradykinin stimulated diacylglycerol production in neuroblastoma cells by
      increasing the hydrolysis of both phosphoinositides and phosphatidylcholine.
      Bradykinin-stimulated production of total diacylglycerol was similar for control
      and L-fucose-conditioned cells. However, there was a decrease in the bradykinin
      induced generation of the 1-stearoyl-2-arachidonoyl diacylglycerol molecular
      species in the cells chronically exposed to 30 mM L-fucose. This molecular
      species accounts for about 70% of the composition of phosphoinositides, but only
      10% of phosphatidylcholine. The results suggest that a decrease in myo-inositol
      uptake results in diminished agonist-induced phosphatidylinositol synthesis and
      phosphoinositide hydrolysis in cultured neuroblastoma cells grown in L-fucose
      containing medium.

PMID- 8263516
TI  - In vivo, ex vivo, and in vitro one- and two-dimensional nuclear magnetic
      resonance spectroscopy of an intracerebral glioma in rat brain: assignment of
      resonances.
AB  - An in vivo study of intracerebral rat glioma using proton-localized NMR
      spectroscopy showed important modifications of the spectra in the tumor as
      compared with the contralateral brain. To carry out the assignment of the
      resonances of the glioma spectra, tumoral and normal rat brain tissues were
      studied in vivo, ex vivo, and in vitro by one-dimensional and two-dimensional
      proton spectroscopy. N-Acetylaspartate was found at an extremely low level in the
      glioma. The change of peak ratio total creatine/3.2 ppm peak was found to be due
      to a simultaneous decrease of the total creatine content and an increase of the
      3.2 ppm peak. The 3.2 ppm resonance in the glioma spectra has been shown to
      originate from choline, phosphocholine, glycerophosphocholine, taurine, inositol,
      and phosphoethanolamine. The increase of the 3.2 ppm peak in the glioma was found
      to result from the increase of taurine and phosphoethanolamine contents. The peak
      in the 1.3 ppm region of the glioma spectra was due to both lactate and mobile
      fatty acids. Moreover, two-dimensional spectroscopy of excised tissues and
      extracts showed the presence of hypotaurine only in the tumor.

PMID- 8263517
TI  - Purification and characterisation of B2 bradykinin receptor from rat uterus.
AB  - A B2 bradykinin (BK) receptor was solubilised and partially purified from rat
      uterine membranes by a combination of ammonium sulphate precipitation, desalting
      on Sephadex G-50, and hydroxyapatite and wheat germ agglutinin affinity
      chromatography. The partially purified BK receptor, enriched 1,500-fold, was then
      cross-linked to 125I-Tyr0-BK using disuccinimidyl suberate and purified to
      homogeneity as a single protein species on two-dimensional gel electrophoresis
      with a molecular mass of 81 kDa. This molecular size was in agreement with the
      value of 80-120 kDa estimated from Sephacryl 300 size exclusion column
      chromatography of the B2 receptor. The partially purified and the crude
      solubilised B2 BK receptor from rat uterus showed similar affinities for BK and
      the BK analogues iodo-Tyr0-Bk, D-Phe7-BK, and des-Arg9-BK, indicating that the
      ligand binding specificity of the receptor had been retained during the
      purification procedures. The biochemical properties of the solubilised B2 BK
      receptor correspond to those of a hydrophobic acidic glycoprotein (isoelectric
      focusing gave a value of 4.5-4.7) that binds specifically to wheat germ
      agglutinin but has no affinity for either concanavalin A or lentil lectin,
      suggesting the absence of terminal mannose or glucose residues.

PMID- 8263518
TI  - Agonist-induced, GTP-dependent phosphoinositide hydrolysis in postmortem human
      brain membranes.
AB  - Membranes prepared from postmortem human brain were used to measure the
      activities of three components of the phosphoinositide second messenger system.
      [3H]Phosphatidylinositol ([3H]PI) hydrolysis was stimulated by directly
      activating phospholipase C with calcium, by activating guanine nucleotide-binding
      proteins (G proteins) with guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) or
      with AIF4, and by receptors activated with several agonists (in the presence of
      GTP gamma S), including (in order of increasing magnitudes of responses)
      carbachol, pilocarpine, histamine, trans-1-aminocyclopentyl-1,3-dicarboxylic acid
      (a selective excitatory amino acid metabotropic receptor agonist), serotonin, and
      ATP. Gq/11 was identified as the G protein most likely to mediate [3H]PI
      hydrolysis in human brain membranes based on the findings that this process was
      not impaired by pretreatment with pertussis toxin and it was inhibited by
      antibodies specific for the alpha-subunit of Gq/11 but not by antibodies for G0
      or Gi1. The effects of postmortem delay on [3H]PI hydrolysis were examined by
      studying tissues obtained 6-21 h postmortem. A slight increase in basal [3H]PI
      hydrolysis was associated with increased postmortem time, suggesting a slow loss
      of the normal inhibitory control of phospholipase C. GTP gamma S-stimulated
      [3H]PI hydrolysis was unaffected by postmortem times within this range, but
      carbachol-induced [3H]PI hydrolysis tended to decrease with increasing postmortem
      times. These results demonstrate that the entire phosphoinositide complex remains
      functional and experimentally detectable in postmortem human brain membranes.
      This method provides a means to study the function, regulation, effects of
      diseases, and responses to drugs of the phosphoinositide system in human brain.

PMID- 8263519
TI  - Preservation of redox, polyamine, and glycine modulatory domains of the N-methyl
      D-aspartate receptor in Alzheimer's disease.
AB  - This study used [3H]dizocilpine ([3H]MK-801) binding to the N-methyl-D-aspartate
      (NMDA) receptor to examine redox, polyamine, and glycine modulatory sites in
      membranes derived from the superior frontal and the superior temporal cortex of
      patients with Alzheimer's disease. In control subjects the competitive polyamine
      site antagonist arcaine inhibited [3H]dizocilpine binding in a dose-dependent
      fashion and this curve was shifted to the right by the addition of 50 microM
      spermidine. Arcaine inhibition of binding was more potent in the temporal cortex
      than in the frontal cortex, in both the absence and presence of 50 microM
      spermidine. In Alzheimer's disease, arcaine inhibition of [3H]dizocilpine binding
      (in both the absence and the presence of spermidine) was not different from
      control in either of the two brain areas examined. The sulfhydryl redox site of
      the NMDA receptor was assessed using the oxidizing agent 5,5'-dithio-bis(2
      nitrobenzoic acid), which inhibited binding in a dose-dependent fashion. This
      inhibition was similar in patients with Alzheimer's disease and control subjects.
      Glycine-stimulated [3H]dizocilpine binding was also unaffected in patients with
      Alzheimer's disease. However, in the temporal cortex there was a significant age
      associated decline in [3H]dizocilpine binding in the presence of 100 microM
      glutamate (Rs = -0.71) and 100 microM glutamate plus 30 microM glycine (Rs = 
      0.90). There was also an age-related increase in arcaine IC50 (which reflects an
      age-related decrease in arcaine affinity) in the frontal cortex, determined both
      in the absence (Rs = 0.83) and the presence (Rs = 0.79) of spermidine. These data
      indicate that the NMDA receptor and its modulatory redox, polyamine, and glycine
      subsites are intact in patients with Alzheimer's disease and that the modulatory
      activity of polyamine and glycine sites decline with aging.

PMID- 8263520
TI  - Brain ion and amino acid contents during edema development in hepatic
      encephalopathy.
AB  - Brain edema in hepatic encephalopathy has been associated with circulating
      ammonia that is metabolized to glutamine. We measured alterations in blood
      chemistry and brain regional specific gravity and ion and amino acid contents in
      models of simple hyperammonemia and liver failure induced by daily
      administrations of ammonium acetate (AAc) or thioacetamide (TAA), respectively.
      Serum and brain ammonia increased to similar levels (200 and 170% of control,
      respectively) in both experimental groups. Serum transaminase activities
      increased 10-fold in animals injected with TAA but were unchanged in animals
      given AAc injections. In both experimental groups glutamine was elevated in
      cerebral white matter, cerebral gray matter, and basal ganglia, whereas brain
      tissue specific gravity decreased in all brain regions, indicating edema
      formation. In the AAc group, we observed a decrease in glutamate and taurine
      contents concomitant with the development of brain edema. In these animals,
      cerebral gray matter specific gravity and taurine contents returned to control
      levels 24 h after the third AAc injection. TAA-injected animals demonstrated
      similar decreases in brain tissue specific gravity, whereas glutamine, glutamate,
      and taurine contents were all elevated. During hepatic encephalopathy, ammonia
      induced changes in brain amino acid content may contribute to brain edema
      development.

PMID- 8263521
TI  - Changes in extracellular and rat brain tissue concentrations of D-beta
      hydroxybutyrate after 1,3-butanediol treatment.
AB  - 1,3-Butanediol (BD) treatment was previously shown to produce a dose-related
      increase of the plasma levels of D-beta-hydroxybutyrate (BHB) and to protect
      brain tissue against hypoxia and ischemia. The purpose of this study was to test
      whether BD-induced hyperketonemia was associated with changes in brain
      extracellular and tissue concentrations of BHB. Changes in extracellular levels
      of BHB were continuously monitored in anesthetized rats before and after
      intraperitoneal injection of BD (25 mmol/kg), using intracerebral microdialysis
      coupled to online analysis of BHB in the dialysate. Cortical tissue
      concentrations of BHB were determined in control and BD-treated rats (25 and 50
      mmol/kg, i.p.) after freezing of the brain in situ. Butanediol produced a rapid
      increase in dialysate levels of BHB, with a linear relationship between dialysate
      and plasma BHB concentrations (r = 0.81, p < 0.001). In contrast, and although
      brain tissue levels of BHB were markedly increased after BD treatment, they were
      not related to the plasma concentration of BHB. Our results suggest that BHB
      produced from BD did not accumulate in brain and that BD protects against hypoxia
      or ischemia by increasing brain BHB availability.

PMID- 8263522
TI  - Tyrosination state of alpha-tubulin in regenerating peripheral nerve.
AB  - Certain modifications of the neuronal cytoskeleton that are associated with
      development also occur during regeneration of adult mammalian peripheral nerve.
      The aim of the present study was to examine one such modification, the
      tyrosination of alpha-tubulin. Adult rats were anaesthetized and the left or
      right sciatic nerve randomly selected and crushed to induce regeneration. In
      certain instances nerves were crushed then ligatured about the crush, to prevent
      regeneration. Five days later the rats were killed and the regenerating (or
      ligatured) and the contralateral (control) nerves were removed. Quantitative
      immunoblotting of nerve homogenates with antibodies that recognize tyrosinated
      alpha-tubulin and total alpha-tubulin revealed a significant increase (p < 0.01)
      in the proportion of alpha-tubulin that was tyrosinated in nerve pieces distal
      (peripheral) to a nerve crush and to uncrushed nerve. No such difference occurred
      in ligatured (crushed but nonregenerating) nerve, implying that the increase was
      related to the presence of regenerating fibres; nor was there any gradient in
      tyrosination of alpha-tubulin in control nerves. This effect was confirmed by
      cytofluorimetric scanning and fluorescence confocal laser scanning microscopy of
      fixed sections of control and regenerating nerve, stained with antibodies
      directed against tyrosinated alpha-tubulin. When nerves were separated into
      fractions containing assembled and nonassembled tubulin, a significant (p < 0.01)
      increase was found in the proportion of tyrosinated alpha-tubulin in the
      nonassembled tubulin fraction in nerve pieces containing regenerating fibres.
      This occurred in the absence of a change in the proportion of assembled and
      nonassembled tubulin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263523
TI  - Sialosylcholesterol effects on reconstitution of microfilament and glia filament.
AB  - The effects of alpha-sialosylcholesterol (alpha-SC) on formation of either
      microfilament or glia filament of rat astrocytes were investigated using a
      reconstitution system. Polymerization of the depolymerized microfilament
      preparation that had been extracted from a crude cytoskeletal fraction of rat
      astrocytes, in the presence of 100 mM KCl and 10 mM MgCl2, was suppressed in a
      dose-dependent manner by alpha-SC. alpha-SC inhibited polymerization of G-actin
      in a similar manner. The intensity of alpha-SC inhibition of G-actin
      polymerization was as great as that of microfilament polymerization, suggesting
      that the inhibition of microfilament polymerization by alpha-SC was due to the
      direct action of alpha-SC on actin, the main component of microfilament. alpha-SC
      depolymerized partly the polymerized microfilament preparation, which resembled F
      actin (microfilament-like filaments). alpha-SC suppressed, in a dose-dependent
      manner, polymerization of a glia filament preparation that had been extracted
      from astrocyte cytoskeletons in the presence of phalloidin. An increase in the
      amount of added alpha-SC (up to 15 microM) decreased the amount of the larger
      glia filament-like filaments, which were 10 nm thick and centrifuged down at
      16,000 g for 30 min, and increased that of smaller ones precipitated only after
      centrifugation at 100,000 g for 1 h. The lower the concentration of the
      depolymerized glia filament extract, the greater was the inhibition by alpha-SC
      of the polymerization. alpha-SC repressed polymerization of vimentin, the
      dominant component of glia filament. Vimentin polymerization was more strongly
      inhibited by alpha-SC than polymerization of glia filament was.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8263524
TI  - Developmental expression of GLUT1 and GLUT3 glucose transporters in rat brain.
AB  - Two glucose transport proteins, GLUT1 and GLUT3, have been detected in brain.
      GLUT1 is concentrated in the endothelial cells of the blood-brain barrier and may
      be present in neurons and glia; GLUT3 is probably the major neuronal glucose
      transporter. Of the few studies of glucose transport in the immature brain, none
      has quantified GLUT3. This study used membrane isolation and immunoblotting
      techniques to examine the developmental expression of GLUT1 and GLUT3 in four
      forebrain regions, cerebral microvessels, and choroid plexus, from rats 1-30 days
      postnatally as compared with adults. The GLUT1 level in whole brain samples was
      low for 14 days, doubled by 21 days, and doubled again to attain adult levels by
      30 days; there was no regional variation. The GLUT3 level in these samples was
      low during the first postnatal week, increased steadily to adult levels by 21-30
      days, and demonstrated regional specificity. The concentration of GLUT1 in
      microvessels increased steadily after the first postnatal week; the GLUT1 level
      in choroid plexus was high at birth, decreased at 1 week, and then returned to
      near fetal levels. GLUT3 was not found in microvessels or choroid plexus. This
      study indicates that both GLUT1 and GLUT3 are developmentally regulated in rat
      brain: GLUT1 appears to relate to the nutrient supply and overall growth of the
      brain, whereas GLUT3 more closely relates to functional activity and neuronal
      maturation.

PMID- 8263525
TI  - Long-chain cis-isoprenyltransferase activity is induced early in the
      developmental program for protein N-glycosylation in embryonic rat brain cells.
AB  - A large developmental increase in Glc3Man9-GlcNAc2-P-P-dolichol (Oligo-P-P-Dol)
      synthesis and protein N-glycosylation in primary cultures of embryonic rat brain
      cells has been reported previously. In vitro enzyme studies and metabolic
      labeling experiments now show that there is a coordinate induction of long-chain
      cis-isoprenyltransferase (IPTase) activity, an activity required for the chain
      elongation stage of dolichyl monophosphate (Dol-P) biosynthesis de novo, and
      Oligo-P-P-Dol biosynthesis in embryonic rat brain. Different developmental
      patterns were observed for IPTase and beta-hydroxy-beta-methyl-glutaryl-CoA (HMG
      CoA) reductase activity as well as Dol-P and cholesterol biosynthesis, indicating
      that these pathways are regulated independently in rat brain. Three separate
      experimental approaches provide evidence that the amount of Dol-P available in
      the rough endoplasmic reticulum (RER) is a rate-limiting factor in the expression
      of the lipid intermediate pathway. First, metabolic labeling experiments show
      that the biosynthesis of Dol-P is induced at the same time or just prior to the
      induction of Oligo-P-P-Dol biosynthesis. Second, the time of induction and rate
      of Oligo-P-P-Dol synthesis are accelerated when Dol-P is supplemented in the
      culture medium. Third, in vitro assays of mannosylphosphoryldolichol synthase and
      N-acetylglucosaminylpyrophosphoryldolichol synthase indicate that there are only
      minor increases in the levels of these enzymes during development, but the amount
      of endogenous Dol-P in the RER that is accessible to the glycosyltransferases
      increases when IPTase activity is induced. In summary, the current studies with
      embryonic rat brain cells document the coordinate induction of IPTase activity
      and Oligo-P-P-Dol synthesis, support the hypothesis that the availability of Dol
      P in the RER is one rate-limiting factor in Oligo-P-P-Dol synthesis, and strongly
      suggest that increases in IPTase activity and the rate of de novo Dol-P
      biosynthesis enhance the capacity of embryonic rat brain cells for lipid
      intermediate synthesis early in the developmental program for N-linked
      glycoprotein biosynthesis.

PMID- 8263526
TI  - Affinity purification of angiotensin type 2 receptors from N1E-115 cells:
      evidence for agonist-induced formation of multimeric complexes.
AB  - The murine neuroblastoma N1E-115 cell line possesses type 1 and type 2
      angiotensin II (AngII) receptor subtypes. In vitro differentiation of these cells
      substantially increases the density of the AT2-receptor subtype, whereas the
      density of the AT1 receptors remains unchanged. In the present study, we report
      that the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate (CHAPS) selectively solubilized AT2 receptors from N1E-115 cell
      membranes and that these receptors could be purified further to near homogeneity
      by affinity chromatography. More specifically, the presence of an agonist (AngII)
      during affinity purification of AT2 receptors resulted in the elution of high
      (110-kDa) and low (66-kDa) molecular mass proteins as determined by gel
      electrophoresis under nonreducing conditions. In contrast, when the nonselective
      antagonist Sar1,Ile8-AngII was used during purification, only the lower 66-kDa
      protein was observed. Affinity purification in the presence of the peptide and
      nonpeptide AT2-receptor antagonists CGP42112A and PD123319 also resulted in
      elution of the same 66-kDa protein, but unlike that in the presence of Sar1,Ile8
      AngII, some of the high molecular weight site was observed as well. On the other
      hand, Losartan, an AT1-receptor antagonist, was completely ineffective in eluting
      any AngII receptors from the affinity column, further confirming their AT2
      identity. After agonist elution, the 110-kDa band dissociated into two low
      molecular mass bands of 66 kDa and 54 kDa when sodium dodecyl sulfate-gel
      electrophoresis was run under reducing conditions.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263527
TI  - The regional distribution of N-acetylaspartylglutamate (NAAG) and peptidase
      activity against NAAG in the rat nervous system.
AB  - N-Acetylaspartylglutamate (NAAG), a prevalent peptide in the vertebrate nervous
      system, may be hydrolyzed by extracellular peptidase activity to produce
      glutamate and N-acetylaspartate. Hydrolysis can be viewed as both inactivating
      the peptide after synaptic release and increasing synaptic levels of ambient
      glutamate. To test the hypothesis that NAAG and the peptidase activity that
      hydrolyzes it coexist as a unique, two-stage system of chemical
      neurotransmission, 50 discrete regions of the rat CNS were microdissected for
      assay. In each microregion, the concentration of NAAG was determined by
      radioimmunoassay and the peptidase activity was assayed using tritiated peptide
      as substrate. The NAAG concentration ranged from 2.4 nmol/mg of soluble protein
      in median eminence to 64 in thoracic spinal cord. Peptidase activity against NAAG
      ranged from 54 pmol of glutamate produced per milligram of membrane protein per
      minute in median eminence to 148 in superior colliculus. A linear relationship
      was observed between NAAG peptidase and NAAG concentration in 46 of the 50 areas,
      with a slope of 2.26 and a correlation coefficient of 0.45. These data support
      the hypothesis that hydrolysis of NAAG to glutamate and N-acetylaspartate is a
      consistent aspect of the physiology and metabolism of this peptide after synaptic
      release. The ratio of peptide concentration to peptidase activity was > 0.3 in
      the following four areas: ventrolateral medulla and reticular formation where the
      peptide is concentrated in axons of passage, thoracic spinal cord, where NAAG is
      concentrated in ascending sensory tracts as well as motoneuron cell bodies, and
      ventroposterior thalamic nucleus.

PMID- 8263528
TI  - Effects of gangliosides GM1 and GD1a on GAP-43 phosphorylation and
      dephosphorylation in isolated growth cones.
AB  - Phosphorylation of the nervous system-specific protein GAP-43 in growth cones in
      vivo increases as the growth cones near their targets, at a time when the
      gangliosides GM1 and GD1a are being accumulated in the growth cone membrane, thus
      raising the possibility that the gangliosides could modulate GAP-43 behavior. We
      used a subcellular fraction of intact isolated growth cones to show that both GM1
      and GD1a affected the calcium-dependent posttranslational regulation of GAP-43 in
      several similar ways. Both gangliosides induced rapid incorporation of phosphate
      into GAP-43; however, the induction was undetectable with our antibody 2G12 that
      is specific for kinase C-phosphorylated GAP-43. Furthermore, neither ganglioside
      stimulated kinase C activity in isolated growth cones, suggesting that the rapid
      phosphorylation may not be on Ser41, the kinase C site. However, both
      gangliosides did induce a slower accumulation of GAP-43 phosphorylated on Ser41,
      apparently by inhibiting a phosphatase. Finally, calcium-dependent proteolysis of
      GAP-43 was also stimulated by both GM1 and GD1a. In contrast, GD1a, but not GM1,
      caused the redistribution of GAP-43 into the isolated growth cone cytoskeleton.
      The results demonstrate that both gangliosides can modulate the calcium-dependent
      regulation of GAP-43.

PMID- 8263529
TI  - Axonal membrane-skeletal protein A60: association with a brain spectrin-binding
      activity and entry into cerebellar axons at a stage after the initiation of
      axonal growth.
AB  - A60 is a 60-kDa component of the axonal cortical cytoskeleton in CNS neurones. It
      appears to be neurone specific and is tightly bound to brain membranes. In this
      study the cytoskeletal activities and developmental expression of A60 in rat
      cerebellum have been examined using the monoclonal antibody DR1. A60 in a
      partially purified soluble extract of brain membranes interacts selectively with
      brain but not erythrocyte spectrin. Because erythrocyte spectrin is more closely
      related to the dendritic form of spectrin than the axonal form, this raises the
      possibility that A60 localises in axons by interaction with the axonal form of
      spectrin only. A60 is not found in rat cerebellum before the day of birth.
      However, during postnatal development of the cerebellum (days 1-13) DR1
      reactivity appears progressively. On postnatal day 1, a small population of cells
      in the mantle layer (presumptive Purkinje cells) is DR1 positive. There is no DR1
      reactivity found in Purkinje cell axons during their initial phase of growth. By
      postnatal day 7, Purkinje cell bodies, initial dendritic segments, and the
      cerebellar white matter are all positive. This pattern of labelling is
      strengthened up until postnatal day 13. By contrast, in adult rat cerebellum, the
      location of A60 has changed so that it is most concentrated in axons, and
      dendritic staining is lost. These data indicate that A60 is a spectrin-binding
      component of the adult axonal membrane skeleton, the presence of which is only
      required in axons after the initial phase of growth.

PMID- 8263530
TI  - Characterization and developmental expression of
      lactotriosylceramide:galactosyltransferase for the synthesis of
      neolactotetraosylceramide in the nervous system.
AB  - Neolactoglycolipids are derived from neolactotetraosylceramide (nLcOse4Cer). They
      are found during the embryonic and neonatal developmental periods in the rat
      cerebral cortex and disappear shortly after birth. These glycolipids are,
      however, abundant in the adult cerebellum. Lactotriosylceramide
      (LcOse3Cer):galactosyltransferase (GT), which catalyzes the terminal step in the
      biosynthesis of nLcOse4Cer, was characterized in mammalian brain. The enzyme was
      highly specific for LcOse3Cer, with a terminal GlcNAc beta 1-3Gal-residue, and it
      did not catalyze the transfer of galactose to other glycolipids studied with
      alternate carbohydrate residues. The microsomal membrane enzyme required Mn2+ and
      a detergent for in vitro activity. The optimal pH was 7.4, and the Km value for
      LcOse3Cer was 34 microM (Vmax = approximately 2 nmol/mg/h). The LcOse3Cer:GT was
      shown to be different from the GM2:GT and the soluble enzyme lactose synthase A.
      The specific activity of LcOse3Cer:GT was enriched fivefold higher in the white
      matter than in the gray matter of young adult rat brain, whereas GM2:GT was
      enriched only about 1.5-fold higher in the white matter. The developmental
      expression of LcOse3Cer:GT in the cerebral cortex and cerebellum was not
      correlative with the levels of nLcOse4Cer in these neural areas. Despite the
      complete absence of nLcOse4Cer in the cerebral cortex of animals older than 5
      days, significant activity of the LcOse3Cer:GT was found even in the adult
      cortex. In cerebellum, the levels of nLcOse4Cer increased with development, but
      the specific activity of the enzyme was reduced by 50% soon after birth and then
      remained practically the same with development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263531
TI  - Tissue-specific expression of isoaspartyl protein carboxyl methyltransferase gene
      in rat brain and testis.
AB  - Isoaspartyl protein carboxyl methyltransferase (PIMT) is widely distributed in
      mammalian tissues. Using a polymerase chain reaction-generated 124-bp DNA
      fragment from brain cDNA as a probe, four different sizes (approximately 4.0,
      2.5, 1.7, and 1.1 kb) of transcripts were detected with northern blot analysis.
      They were expressed predominantly in rat brain and testis. The major transcripts
      were 2.5 and 1.7 kb in the brain and 2.5 and 1.1 kb in the testis. One of the
      major transcripts specific to the testis (1.1 kb) was determined to study the
      structural difference of major transcripts in the two tissues. This testicular
      cDNA had neither the 5' (94 nucleotides) nor the 3' (594 nucleotides) end of
      previously reported brain cDNA corresponding to 1.7 kb. The mRNA levels and
      enzyme activities of different regions and developmental changes were examined in
      the brain. The mRNA levels and enzyme activities were concomitantly high in
      cerebral cortex and hippocampus. Although they increased rapidly approximately 30
      days after birth in the testis and decreased in aged rats, they increased
      gradually after birth and remained high during the aging of the brain. Both
      structural and developmental studies show that the expression of the PIMT gene in
      brain and testis is regulated in a tissue-specific manner.

PMID- 8263532
TI  - Evidence that the major membrane lipids, except cholesterol, are made in axons of
      cultured rat sympathetic neurons.
AB  - Membrane lipids and proteins required for axonal growth and regeneration are
      generally believed to be synthesized in the cell bodies of neurons and
      transported into the axons. However, we have demonstrated recently that, in
      cultured rat sympathetic neurons, axons themselves have the capacity to
      synthesize phosphatidylcholine, sphingomyelin, and phosphatidylethanolamine. In
      these experiments, we employed a compartment model of neuron culture in which
      pure axons grow in a fluid environment separate from that containing the cell
      bodies. In the present study, we again used compartmented cultures to confirm and
      extend the previous results. We have shown that three enzymes of
      phosphatidylcholine biosynthesis via the CDP-choline pathway are present in
      axons. We have also shown that the rate-limiting step in the biosynthesis of
      phosphatidylcholine by this route in neurons, and locally in axons, is catalyzed
      by the enzyme CTP:phosphocholine cytidylytransferase. The biosynthesis of other
      membrane lipids, such as phosphatidylserine, phosphatidylethanolamine derived by
      decarboxylation of phosphatidylserine, phosphatidylinositol, and fatty acids,
      also occurs in axons. However, the methylation pathway for the conversion of
      phosphatidylethanolamine into phosphatidylcholine appears to be a quantitatively
      insignificant route for phosphatidylcholine synthesis in neurons. Moreover, our
      data provided no evidence for the biosynthesis of another important membrane
      lipid, cholesterol, in axons.

PMID- 8263533
TI  - [3H]GBR-12935 binding to human cerebral cortex is not to dopamine uptake sites.
AB  - The binding of the dopamine uptake inhibitor [3H]GBR-12935 to 16 regions of the
      human brain was investigated in competition experiments with increasing
      concentrations of GBR-12909, mazindol, and dopamine. The methodology used
      included a relatively high tissue concentration (8 mg/ml) and addition of 5 mM
      KCl in the assay buffer. GBR-12909 inhibited 80-90% of the binding in most
      regions, whereas dopamine only inhibited the binding in the striatum. Mazindol
      inhibited only part of the cortical binding at concentrations of > 1 microM,
      whereas the inhibition in the caudate and the putamen also contained a high
      affinity component representing the dopamine uptake site. It is concluded that
      the [3H]GBR-12935 binding sensitive to GBR-12909 cannot be regarded as specific
      binding to the dopamine uptake site because the displaceable binding most likely
      is not related to the dopamine uptake site.

PMID- 8263534
TI  - [3H]GBR-12935 binding to cytochrome P450 in the human brain.
AB  - The presence of multiple [3H]GBR-12935 binding sites in the human brain has been
      revealed in several recent studies. One site represents the dopamine uptake site.
      In rat brain it was demonstrated that [3H]GBR-12935 also binds to nondopaminergic
      "piperazine acceptor sites." One of these sites has been identified as cytochrome
      P450IID1 in canine brain. [3H]GBR-12935 binding to the piperazine acceptor sites
      in the human brain was investigated in the present study. A pharmacological
      definition of the piperazine acceptor sites is presented: the [3H]GBR-12935
      binding fraction that could be discriminated by 10 microM GBR-12909 in the
      presence of 0.3 microM mazindol. This binding fraction was saturable, with
      binding affinity in the range of 3-8 nM. It was also demonstrated that the
      piperazine acceptor or cytochrome P450-sensitive drugs cis-flupentixol and
      proadifen (SKF 525 A) compete for the same binding sites, suggesting the
      cytochrome P450 nature of the binding. The findings presented support the
      proposal that at least part of this fraction represents cytochrome P450IID6, the
      human form of P450IID1. The distribution of [3H]GBR-12935 binding to the
      suggested P450IID6-site in 12 brain regions was examined, without significant
      differences in binding densities between the regions. The significance of the
      present findings on the cytochrome P450 system in brain is discussed.

PMID- 8263535
TI  - NMR identification of the formic acid-modified residue in Alzheimer's amyloid
      protein.
AB  - The beta/A4-amyloid protein (beta/A4) and many synthetic fragments of this
      protein have proved to be very difficult to solubilize, leading to the use of
      relatively harsh chemical methods, most notably, formic acid. This treatment has
      previously been shown to cause a covalent modification of this peptide. In this
      study, one- and two-dimensional NMR techniques are used to show that the nature
      of this covalent modification is formation of a formate ester to a serine
      residue. This finding is consistent with our previously reported kinetic studies
      of formic acid-induced modification of beta/A4 and further illustrates the
      potential danger of solubilizing fragments of beta/A4 in formic acid. Alternative
      methods of solubilization are discussed.

PMID- 8263536
TI  - Role of Mg-ATP in norepinephrine biosynthesis in intact chromaffin granules.
AB  - Dopamine beta-monooxygenase converts dopamine to norepinephrine in intact
      chromaffin granules using intragranular ascorbic acid as a cosubstrate. Mg-ATP
      with external ascorbic acid is required for maximal norepinephrine biosynthesis.
      Mechanisms to explain these requirements were investigated specifically using
      intact granules. The effect of Mg-ATP was independent of membrane potential
      (delta psi) because norepinephrine biosynthesis was unchanged whether delta psi
      was positive or collapsed. Furthermore, the effect of Mg-ATP was independent of
      absolute intragranular and extragranular pH as well as the pH difference across
      the chromaffin granule membrane (delta pH). Nevertheless, norepinephrine
      biosynthesis was inhibited by N-ethylmaleimide, 4-chloro-7-nitrobenzofurazane,
      and N,N-dicyclohexylcarbodiimide, specific inhibitors of the secretory vesicle
      ATPase that may directly affect proton pumping. Biosynthesis occurred normally
      with other ATPase inhibitors that do not inhibit the ATPase in secretory
      vesicles. The data indicate that the effect of Mg-ATP with ascorbic acid is
      mediated by the granule membrane ATPase but independent of maintaining delta psi
      and delta pH. An explanation of these findings is that Mg-ATP, via the granule
      ATPase, may change the rate at which protons or dopamine are made available to
      dopamine beta-monooxygenase.

PMID- 8263537
TI  - Compared binding properties of 125I-labeled analogues of neurotensin and
      neuromedin N in rat and mouse brain.
AB  - Neurotensin and neuromedin N are two structurally related peptides that are
      synthesized by a common precursor. The purpose of the present work was to
      characterize neuromedin N receptors in rat and mouse brain and to compare these
      receptors with those of neurotensin. A radiolabeled analogue of neuromedin N has
      been prepared by acylation of the N-terminal amino group of the peptide with the
      125I-labeled Bolton-Hunter reagent. This 125I-labeled derivative of neuromedin N
      bound to newborn mouse brain homogenate with high affinity (KD = 0.5 nM). Cross
      competition experiments between radiolabeled and unlabeled neurotensin and
      neuromedin N indicated that each peptide was able to displace completely and
      specifically the other peptide from its interaction with its receptor.
      Independently of the radioligand used, the affinity of neurotensin was always
      better than that of neuromedin N. Quantitative radioautographic studies
      demonstrated that the ratio of labeling intensities obtained with 125I-labeled
      analogues of neurotensin and neuromedin N remained constant in all the brain
      areas. Our results do not support the existence of a specific neuromedin N
      receptor in rat and mouse brain and can be explained by the presence of a common
      receptor for both peptides.

PMID- 8263538
TI  - Evidence for a glycidic-lipidic matrix in human neuromelanin, potentially
      responsible for the enhanced iron sequestering ability of substantia nigra.
AB  - The high-resolution solid-state 13C-NMR spectrum of a neuromelanin specimen (from
      patients dying from nonneurological diseases) is compared with that obtained from
      enzymatically prepared dopamine-melanin. The main differences between the two
      spectra suggest the occurrence in neuromelanin of a glycidic/lipidic matrix
      tightly associated with the melanin macromolecule. Atomic emission spectroscopy
      revealed high iron content (1.5%) in the neuromelanin specimen, in full agreement
      with previous reports. These observations support the view that neuromelanin acts
      as a strong chelating (and insolubilizing) system for iron ions and further
      suggest that the attack to this compact composite substrate may be an important
      step to allow the release of iron ions responsible for the increased lipid
      peroxidation reported in the pathogenesis of Parkinson's disease.

PMID- 8263539
TI  - Hydroxyl radicals generated in vivo kill neurons in the rat spinal cord:
      electrophysiological, histological, and neurochemical results.
AB  - We have used microdialysis to establish an experimental model to characterize
      mechanisms whereby released substances cause secondary damage in spinal cord
      injury. We use this model here to characterize damaging effects of the hydroxyl
      radical (OH.) in vivo in the spinal cord. OH. was generated in vivo by pumping
      H2O2 and FeCl2/EDTA through parallel microdialysis fibers inserted into the
      spinal cord. These agents mixed in the tissue to produce OH. by Fenton's
      reaction. Two types of control experiments were also conducted, one administering
      only 5 mM H2O2 and the other only 0.5 mM FeCl2/0.82 mM EDTA. During
      administration of these chemicals, electrical conduction was recorded as one test
      for deterioration. OH. blocked conduction completely in 2.5-5 h and Fe2+/EDTA
      partly blocked conduction, but H2O2 alone did not cause detectable blockage.
      Histological examination supported the hypothesis that neurons were killed by
      OH., as Fe2+/EDTA and H2O2 alone did not destroy significant numbers of neurons.
      OH., H2O2, and Fe2+ all caused gradual increases in extracellular amino acid
      levels. These results are consistent with Fe(2+)-catalyzed free radical
      generation playing a role in tissue damage upon spinal cord injury.

PMID- 8263540
TI  - Ca2+ channel blockers attenuate beta-amyloid peptide toxicity to cortical neurons
      in culture.
AB  - Deposit of beta-amyloid protein (A beta) in Alzheimer's disease brain may
      contribute to the associated neurodegeneration. We have studied the neurotoxicity
      of A beta in primary cultures of murine cortical neurons, with the aim of
      identifying pharmacologic ways of attenuating the injury. Exposure of cultures to
      A beta (25-35 fragment; 3-25 microM) generally triggers slow, concentration
      dependent neurodegeneration (over 24-72 h). With submaximal A beta-(25-35)
      exposure (10 microM), substantial (> 40% within 48 h) degeneration often occurs
      and is markedly attenuated by the presence of the Ca2+ channel blockers
      nimodipine (1-20 microM) and Co2+ (100 microM) during the A beta exposure.
      However, A beta neurotoxicity is not affected by the presence of glutamate
      receptor antagonists. We suggest that Ca2+ influx through voltage-gated Ca2+
      channels may contribute to A beta-induced neuronal injury and that nimodipine and
      Co2+, by attenuating such influx, are able to attenuate A beta neurotoxicity.

PMID- 8263541
TI  - Cu/Zn superoxide dismutase activity in familial and sporadic amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a degenerative motor neuron disease that
      is inherited as an autosomal dominant trait in approximately 10% of cases.
      Recently we and others identified several single-base mutations in the Cu/Zn
      superoxide dismutase (SOD1) gene in patients with familial ALS (FALS). Using
      single-strand conformational polymorphism, we studied the C to G mutation in exon
      2 of the SOD1 gene (resulting in a leucine to valine substitution in position 38)
      in affected and unaffected members of a large Belgian family with FALS. We
      measured the SOD1 activity in red blood cell lysates in 14 members of this
      family, including the only surviving clinically affected patient. SOD1 activity
      of the family members carrying the mutation was less than half that of members
      without the mutation. In addition, in 11 patients with sporadic ALS and 11 age-
      and sex-matched controls, red blood cell SOD1 activity was normal. These studies
      indicate that SOD1 activity is reduced in these FALS patients but not in sporadic
      ALS patients. Moreover, this SOD1 enzyme abnormality is detectable years before
      onset of clinical ALS in carriers of this FALS mutation.

PMID- 8263542
TI  - cis-Methyldioxolane specifically recognizes the m2 muscarinic receptor.
AB  - cis-Methyldioxolane (CD) is a muscarinic receptor agonist. [3H]CD has been used
      to label a subpopulation of muscarinic receptors described as exhibiting high
      agonist affinity. Pharmacological evidence suggests that the population of
      receptors labeled by [3H]CD consists of m2 and/or m4 subtypes; however, no
      studies have directly addressed the subtype selectivity of [3H]CD. The present
      study characterizes binding of this ligand to individual human receptor subtypes
      expressed in transfected Chinese hamster ovary cells. Results indicate that
      [3H]CD binds with high affinity only to Hm2 receptors but not to all Hm2
      receptors. Twenty-eight percent of Hm2 receptors bound [3H]CD with a KD of 3.5 +/
      0.5 nM. Binding was eliminated in the presence of guanosine 5'-O-(3
      thiotriphosphate), indicating that the Hm2 receptors labeled by [3H]CD are those
      that are associated with GDP-bound G protein. Binding of [3H]CD by only a
      subpopulation of Hm2 receptors is in agreement with data generated from studies
      of [3H]CD binding in mammalian brain. Because muscarinic receptors have been
      implicated to play a role in the pathogenesis of both Alzheimer's and Parkinson's
      disease, as well as the neurotoxicity of organophosphorus compounds, knowledge of
      the binding specificity of the muscarinic agonist [3H]CD should aid research in
      these areas.

PMID- 8263543
TI  - A cis-acting element, T alpha-1, in the upstream region of rod alpha-transducin
      gene that binds a developmentally regulated retina-specific nuclear factor.
AB  - The G protein transducin (T) is an integral component of the signal transduction
      pathway in photoreceptors. We have identified a cis-acting element, T alpha-1, in
      the upstream region of the mouse rod alpha-T (Tr alpha) gene that may be
      important for tissue-specific expression. T alpha-1 binds a retina-specific
      nuclear factor of apparent molecular mass of 90 kDa. Binding to the T alpha-1
      site is developmentally regulated and peaks between postnatal days 6 and 9. This
      corresponds to the time of rod photoreceptor maturation and the rise in Tr alpha
      gene expression. The sequence of T alpha-1 shows homology with RET-1, a cis
      acting element in the proximal promoter of opsin gene that binds a distinct
      retina-specific factor. T alpha-1 and RET-1 sequences may have been derived from
      a prototype T alpha-1/RET-1 sequence, evolved to confer photoreceptor specificity
      on retina-specific genes.

PMID- 8263544
TI  - Neuropeptide expression and processing as revealed by direct matrix-assisted
      laser desorption ionization mass spectrometry of single neurons.
AB  - Neuropeptides were directly detected in single identified neurons and the
      neurohemal area of peptidergic (neuroendocrine) systems in the Lymnaea brain by
      using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS).
      The samples were placed in matrix solution and ruptured to allow mixing of cell
      contents with the matrix solution. After formation of matrix crystals, the
      analytes were analyzed by MALDI-MS. It was surprising that clean mass spectra
      were produced, displaying extreme sensitivity of detection. In one of the
      neuroendocrine systems studied, we could demonstrate for the first time, by
      comparing the peptide patterns of soma and of neurohemal axon terminals, that
      processing of the complex prohormone expressed in this system occurs entirely in
      the soma. In the other system studied, novel peptides could be detected in
      addition to peptides previously identified by conventional molecular biological
      and peptide chemical methods. Thus, complex peptide processing and expression
      patterns could be predicted that were not detected in earlier studies using
      conventional methods. As the first MALDI-MS study of direct peptide
      fingerprinting in the single neuron, these experiments demonstrate that MALDI-MS
      forms a new and valuable approach to the study of the synthesis and expression of
      bioactive peptides, with potential application to single-cell studies in
      vertebrates, including humans.

PMID- 8263545
TI  - Elevated levels of glucose and L-fucose reduce 22Na+ uptake and whole cell Na+
      current in cultured neuroblastoma cells.
AB  - Na+ flux was studied in cultured neuroblastoma cells grown in medium containing
      increased glucose or L-fucose concentrations. Chronic exposure of neuroblastoma
      cells to 30 mM glucose or 30 mM L-fucose caused a decrease in ouabain-sensitive
      and veratridine-stimulated 22Na+ uptake compared with cells cultured in
      unsupplemented medium. The Na+ current, determined by using whole-cell
      configuration of the patch clamp, was also decreased in these cells. Tetrodotoxin
      (3 microM), which blocked whole cell Na+ currents, also blocked veratridine
      stimulated 22Na+ accumulation. Culturing cells in medium containing 30 mM
      fructose as an osmotic control had no effect on Na+ flux. Specific [3H]saxitoxin
      binding was not affected by 30 mM glucose or 30 mM L-fucose compared with cells
      grown in unsupplemented medium, suggesting that the number of Na+ channels was
      not decreased. These studies suggest that exposing cultured neuronal cells to
      conditions that occur in the diabetic milieu alters Na+ transport and Na(+)
      channel activity.

PMID- 8263546
TI  - GABAergic modulation of striatal cholinergic interneurons: an in vivo
      microdialysis study.
AB  - Striatal cholinergic interneurons have been shown to receive input from striatal
      gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on
      two different types of receptors, the GABAA and the GABAB receptor. Using in vivo
      microdialysis, we have studied the effect of intrastriatal application of the
      GABAA-selective compounds muscimol and bicuculline and the GABAB-selective
      compounds baclofen and 2-hydroxysaclofen, agonists and antagonists, respectively,
      at GABA receptors, on the output of striatal acetylcholine (ACh). Intrastriatal
      infusion of 1 and 10 mumol/L concentrations of the GABAA antagonist bicuculline
      resulted in a significant increase in striatal ACh output, whereas infusion of 1
      and 10 mumol/L concentrations of the GABAA agonist muscimol significantly
      decreased the output of striatal ACh. Both compounds were ineffective in changing
      the output of striatal ACh at lower concentrations. Infusion of concentrations up
      to 100 mumol/L of the GABAB-selective antagonist 2-hydroxy-saclofen failed to
      affect striatal ACh output, whereas infusion of 10 and 100 mumol/L baclofen, but
      not 0.1 and 1 mumol/L baclofen, significantly decreased the output of striatal
      ACh. Thus, agonist-stimulation of GABAA and GABAB receptors decreases the output
      of striatal ACh in a dose-dependent fashion, whereas the GABAAergic system
      appears to inhibit tonically the output of striatal ACh via GABAA receptors, but
      not via GABAB receptors. We hypothesize that although GABAA mediated regulation
      of striatal ACh occurs via GABA receptors on the cholinergic neuron, the GABAB
      mediated effects may be explained by presynaptic inhibition of the glutamatergic
      input of the striatal cholinergic neuron.

PMID- 8263547
TI  - Glycolipids isolated from Aplysia kurodai can activate cyclic adenosine 3',5'
      monophosphate-dependent protein kinase from rat brain.
AB  - Cyclic AMP (cAMP)-dependent protein kinase (cAMP-kinase) partially purified from
      the membrane fractions of rat brains was stimulated by novel
      phosphonoglycosphingolipids (glycolipids) derived from the skin and nerve fibers
      of Aplysia kurodai. Among various glycolipids tested, a major glycolipid from the
      skin, 3-O-MeGal beta 1-->3GalNAc alpha 1-->3[6'-O-(2-aminoethylphosphonyl)Gal
      alpha 1-->2](2-aminoethylphosphonyl-->6)Glc beta 1-->4Glc beta 1-->1ceramide (SGL
      II), was most potent, giving half-maximal activation at 32.2 microM. Activation
      of cAMP-kinase was maximal with 250 microM SGL-II using kemptide as substrate.
      The effect of SGL-II was additive on kinase activity at submaximal concentrations
      of cAMP. The kinase activity activated with SGL-II was inhibited by the addition
      of protein kinase inhibitor peptide, a specific peptide inhibitor for cAMP
      kinase. Its inhibitory pattern was similar to that for the catalytic subunit. Of
      the various substrates tested, the glycolipid-stimulated cAMP-kinase could
      phosphorylate microtubule-associated protein 2, synapsin I, and myelin basic
      protein but not histone H1 and casein. The regulatory subunit strongly inhibited
      the activity of purified catalytic subunit of cAMP-kinase. This inhibition was
      reversed by addition of SGL-II, as observed for cAMP. SGL-II was capable of
      partially dissociating cAMP-kinase, which was observed by gel filtration column
      chromatography. However, the binding activity of cAMP to the holoenzyme was not
      inhibited with SGL-II. These results demonstrate that the glycolipids can
      directly activate cAMP-kinase in a manner similar, but not identical, to that of
      cAMP.

PMID- 8263548
TI  - Modulatory effects of testosterone on 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine-induced neurotoxicity.
AB  - In this experiment, we examined the modulatory effects of testosterone on the
      parkinsonism-inducing drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in
      two strains of mice. Orchidectomized male CD-1 and C57/B1 mice were implanted
      with either empty Silastic capsules or capsules containing testosterone and
      subsequently treated with MPTP. A small area of the corpus striatum was removed
      for determination of dopamine (DA) content, whereas the remainder was superfused
      and used to measure L-DOPA (5 microM)-evoked DA release. In animals treated with
      MPTP, L-DOPA-evoked DA release was reduced significantly in CD-1 mice, but not in
      C57/B1 mice, treated with testosterone. No differences in L-DOPA-stimulated DA
      release between MPTP-versus vehicle-treated mice was observed in either the CD-1
      or C57/B1 mice receiving empty Silastic capsules. Corpus striatum DA contents
      were more severely depleted in the MPTP-sensitive C57/B1 versus the CD-1 mouse
      strain irrespective of hormone treatment. These results confirm previous results
      demonstrating differences in these two mouse strains in response to the
      neurotoxic effects of MPTP upon corpus striatum DA content. More interestingly,
      they show an important differential modulatory effect of testosterone upon L-DOPA
      evoked DA release as a function of MPTP treatment and indicate that testosterone
      significantly alters the neurotoxic effects of MPTP in the CD-1 mouse.

PMID- 8263549
TI  - Dystrophin abnormalities in Duchenne and Becker dystrophy carriers: correlation
      with cytoskeletal proteins and myosins.
AB  - Characterization with a panel of six antibodies revealed abnormal dystrophin
      expression in 6 of 20 Duchenne muscular dystrophy (DMD) carriers examined, and in
      5 of 12 Becker muscular dystrophy (BMD) carriers examined. The
      immunocytochemistry of muscle fibres was normal with five of the antibodies in
      two BMD carriers, but some muscle fibres were negative to the antibody directed
      against a portion of the dystrophin rod domain. Mosaicism was detected with all
      six antibodies in the other three BMD (but in only a small number of fibres) and
      in all DMD carriers muscles. Spectrin, vinculin and talin were immunolocalized in
      the same muscle specimens in order to assess membrane cytoskeletal integrity and
      to correlate their expression with that of dystrophin. These proteins, including
      vinculin, which was previously reported to be reduced in DMD patient muscles,
      were normally present on the surface of all dystrophin-deficient fibres. Muscle
      fibre types were characterized using monoclonal antibodies against fetal myosin
      and adult fast and adult slow myosin heavy chains. In both the DMD and BMD
      carriers, a significant reduction in type 2B fibres, as well as an increase in
      type 2C and fetal myosin-containing fibres was found - as has also been reported
      in DMD patients. Altered dystrophin expression was observed more frequently in
      type 2 than type 1 fibres. Dystrophin deficiency was found in a high percentage
      of type 2C fibres as well as in all fibres expressing fetal myosin; this suggests
      that dystrophin-deficient fibres are more susceptible to degeneration, leading to
      regeneration.

PMID- 8263550
TI  - Wallenberg's lateral medullary syndrome with loss of pain and temperature
      sensation on the contralateral face: clinical, MRI and electrophysiological
      studies.
AB  - Thirteen patients with Wallenberg's lateral medullary syndrome (WLMS) were
      studied. Clinical and magnetic resonance imaging (MRI) evidence demonstrated
      infarction in the dorsolateral medulla which produced loss of pain and
      temperature sensation on one side of the face ipsilateral to the lesion in seven
      patients. However, in another six patients, the infarction in a similar location
      produced the same sensory loss on the contralateral face. This is the first
      report of an analysis comparing these two conditions in WLMS patients, confirmed
      by MRI. The finding of normal blink reflex and somatosensory evoked potentials
      (stimulation on median nerve) in the two groups of patients may indicate that the
      impulses travel along the central pathways of touch, vibration and joint position
      sensation instead of the pathways for pain and temperature, because the patients
      had normal sensation of touch, vibration and joint position but impairment of
      pain and temperature sensation. In addition, it is suggested that the pathways of
      late blink reflex (R2) pass through the medial lemniscus in the ventromedial
      medulla instead of the spinal trigeminal tract in the dorsolateral medulla.
      Further, the observation of the much longer lantencies (about 29 ms) of the
      normal R2 raises the possibility that the impulses may travel along the longer
      pathways through the opposite medial lemniscus and up to the thalamus or cortex
      where they project to bilateral motoneurons of the orbicularis oculi muscles.
      Although the alternative of R2 travelling only by the shorter pathways through
      the brain stem is not excluded, this is not supported by current data.

PMID- 8263551
TI  - Pain, muscle spasms and twitching fingers following brachial plexus avulsion.
      Report of three cases relieved by dorsal root entry zone coagulation.
AB  - Three patients who, following partial brachial plexus avulsion, experienced pain,
      involuntary finger twitching and muscular spasms are reported. Two exhibited
      cutaneous trigger zones, stimulation of which exacerbated their pain; changes in
      emotional tone aggravated both the pain and the spasms. Pain would appear to be
      due not only to deafferentation and scarring of the dorsal horn, but also to an
      afferent pathological barrage from partially damaged dorsal roots. The
      pathological sensory barrage may activate metameric interneuronal circuits and
      produce involuntary movements. Exacerbation of both the pain and the spasms can
      be explained on the basis of intrinsic properties of these ectopic pacemakers.

PMID- 8263552
TI  - Reactivity of locally produced CSF antibodies in patients with neurosyphilis
      against antigens of Treponema pallidum.
AB  - The reactivity and specificity of locally produced cerebrospinal fluid (CSF)
      antibodies against antigens of Treponema pallidum were assessed by Western
      blotting in patients with clinical signs of parenchymal or meningovascular
      neurosyphilis. All nine patients showed local production of treponeme-specific
      antibodies in the central nervous system (CNS). In most of the patients serum and
      CSF antibodies were bound to the same antigens: the common treponemal 48/45 kDa
      protein and the putative specific T. pallidum protein in the range of 12-14 kDa.
      In some patients the intensity of staining obtained by CSF antibodies was higher
      than that derived from serum, indicating locally produced antibodies. In contrast
      to other more acute inflammatory CNS diseases, no expanded or different antigen
      binding of the CSF antibodies compared with serum antibodies was found in
      neurosyphilic patients. The results presented are discussed with regard to the
      role of the blood-brain barrier in antibody concentrations of CSF and serum.

PMID- 8263553
TI  - Oculomotor abnormalities in motor neuron disease.
AB  - To determine whether there are oculomotor abnormalities in motor neuron disease
      (MND), electro-oculographic recordings were performed prospectively in 16 MND
      patients and the results compared with age-matched healthy controls. Parameters
      analysed included random and fixed saccades (latency, velocity and accuracy),
      smooth pursuit (gain, total harmonic distortion and number of saccadic
      intrusions) and optokinetic nystagmus (maximal and mean slow component velocity).
      Increased saccadic latencies and decreased smooth pursuit gain were the main
      alterations in the MND group. Correlation with clinical variables showed a
      positive relationship between smooth pursuit saccadic intrusions and the bulbar
      clinical score and the rate of progression and a lower optokinetic nystagmus
      maximal velocity in patients with pseudobulbar syndrome. Our results demonstrate
      the presence of subclinical supranuclear abnormalities in MND, and support the
      notion that MND is not merely a degeneration of the motor system.

PMID- 8263554
TI  - Muscle disease, HIV and zidovudine: the spectrum of muscle disease in HIV
      infected individuals treated with zidovudine.
AB  - Eleven patients with AIDS or AIDS-related complex who developed muscle-related
      symptoms whilst taking zidovudine were investigated. The clinical details of a
      further ten patients who did not undergo muscle biopsy are also outlined. The
      clinical features, quantitative muscle strength testing, electromyographic
      findings, serial creatine kinase levels, muscle biopsy appearance on light
      microscopy and the effects of zidovudine withdrawal and rechallenge are
      described. The spectrum of muscle disease encountered included four cases of
      frank myopathy diagnosed using clinical, electrophysiological and histological
      criteria, four patients with mild weakness and myalgia in whom muscle biopsies
      were normal, three patients with myalgia only and a mild increase in the
      interstitial cell infiltrate shown by biopsy. The patients presenting with
      myopathy showed no improvement on withdrawal of zidovudine but responded to
      immunosuppressive therapy with steroids and, in one case, thalidomide prescribed
      incidentally. At present, it is not yet possible to clinically define a specific
      zidovudine-induced myopathy that is distinct from the other effects of HIV
      infection on muscle structure and function. Our experience suggests that
      zidovudine may be implicated as a myotoxin in some patients, particularly those
      with myalgia and mild weakness. In those patients with severe weakness, and with
      biopsy findings of necrosis and inflammation, the drug effects may be difficult
      to separate from the primary effects of HIV.

PMID- 8263555
TI  - Visual evoked potentials after optic neuritis. Effect of time interval, age and
      disease dissemination.
AB  - Visual evoked potentials (VEPs) were compared among six groups of patients tested
      at various times after an episode of acute unilateral optic neuritis (ON). The
      incidence of abnormalities ranged from above 90% in patients tested during the
      first 6 months to about 70% when more than 2 years had elapsed. Compared with the
      acute stage (1-8 weeks), latency prolongation was almost 50% less in patients
      tested after 2-19 years. In the latter group, latencies were significantly
      correlated with the patients' age at the time of the attack. The findings confirm
      and extend the evidence of serial studies which shows that the shortening of VEP
      latency is a general phenomenon which proceeds for up to 2 years and possibly for
      longer in younger patients. When the patients with clinically isolated ON were
      compared with those who had a history of additional neurological episodes
      suggestive of multiple sclerosis (MS), up to 4 weeks after ON latencies were more
      prolonged in the MS group but between 4 and 8 weeks amplitudes were larger and
      between 8 weeks and 2 years latencies were significantly shorter. No significant
      differences were found in patients tested after more than 2 years. It is
      suggested that the electrophysiological deficit may initially be more severe in
      patients with disseminated disease, but that recovery may occur faster.

PMID- 8263556
TI  - Primitive reflexes in healthy, adult volunteers and neurological patients:
      methodological issues.
AB  - A study was made to determine whether two experienced clinicians elicited and
      scored primitive reflexes (PR) differently and whether reliability could be
      improved by standardization. Three studies were carried out, using a protocol for
      the examination of 14 PR. In the first study with 31 healthy young subjects, two
      investigators found virtually no difference in the routine neurological
      examination. However, the interobserver agreement was very poor, indicating the
      need for a further improvement of the PR protocol. In the second study, 30
      neurological patients were examined with an improved, more explicit and
      standardized protocol, in which the amplitude and the persistence of the reflex
      were scored separately. Interobserver agreement improved considerably, and was
      high for amplitude as well as persistence. In the third study, 36 neurological
      patients were examined twice by one investigator within 2 weeks. Good to
      excellent intraobserver agreement was found. No pathognomonic or strictly
      localizing reflex could be distinguished.

PMID- 8263557
TI  - Cerebellar encephalitis in adults.

PMID- 8263558
TI  - Guillain-Barre syndrome during treatment with ofloxacin.

PMID- 8263559
TI  - Isolated postural tremor revealing HIV-1 infection.

PMID- 8263560
TI  - Probable exacerbation of myasthenia gravis by ofloxacin.

PMID- 8263561
TI  - The quality of epidemiological data in coronary heart disease and
      atherosclerosis.
AB  - There are inherent difficulties in the use of indirect observations in the
      epidemiology of a chronic ubiquitous disease such as atherosclerosis. Such
      difficulties do not condone basic errors in epidemiological methodology, the use
      of low quality data, a lack of precision in measurements, invalid extrapolations
      and inappropriate use of terminology and coronary heart disease as a surrogate or
      synonym of coronary atherosclerosis and bias in the interpretation of data. These
      errors reveal a lack of rigorous and scientific standards in the epidemiology of
      coronary heart disease. Analysis cannot launder such data. Independent scientists
      must evaluate the data in respect of precision, logic and truth.

PMID- 8263562
TI  - "Consider what a long way you've come"--the white queen to Alice.

PMID- 8263563
TI  - What is truth said Pontius Pilate and would not wait for an answer: a biological
      reply to Dr Stehbens.

PMID- 8263564
TI  - "Rainbow reviews." VI: Recent publications of the National Center for Health
      Statistics.

PMID- 8263565
TI  - Serum insulin and ECG abnormalities suggesting coronary heart disease in the
      populations of Mauritius and Nauru: cross-sectional and longitudinal
      associations.
AB  - Cross-sectional associations between insulin and ECG abnormalities suggestive of
      'possible' and 'probable' coronary heart disease (CHD) in the populations of
      Nauru (n = 568) and Mauritius (n = 3280) have been examined in both non-diabetic
      and diabetic subjects. Additionally, the longitudinal relationship between
      baseline insulin and incident ECG abnormalities has been explored in non-diabetic
      Nauruans (n = 177) over 5 years. Age-adjusted mean 2-hour serum insulin was
      generally higher in subjects with ECG abnormalities than those with a normal ECG,
      but the difference was significant only for non-diabetic Mauritian men (p <
      0.01). There was no clear association between prevalence of ECG abnormalities and
      quintiles of fasting or 2-hr insulin in Mauritians, and in non-diabetic Nauruans
      there was a non-significant positive association between prevalence of ECG
      abnormalities and tertiles of 2-hr insulin. Logistic regression analyses showed a
      slight positive association between 2-hr insulin and ECG abnormalities in non
      diabetic Mauritians (p = 0.06 in males, p = 0.09 in females), and non-diabetic
      male Nauruans (p = 0.054) independent of possible confounders. Fasting insulin
      was not associated in any group. In longitudinal analyses in Nauruans there were
      no significant differences in mean baseline fasting or 2-hr serum insulin between
      subjects who maintained a normal ECG and those who developed abnormalities
      consistent with 'possible CHD' (there were no changes suggestive of 'probable
      CHD'). The incidence of ECG changes suggesting 'possible CHD' was slightly higher
      in the upper tertile of baseline fasting insulin in both sexes and 2-hr insulin
      in females, but when other factors were accounted for, multiple logistic
      regression analyses did not support this finding. Data from the populations of
      Mauritius and Nauru do not support a major role for serum insulin in ECG
      abnormalities suggestive of CHD.

PMID- 8263566
TI  - Relapse following emergency treatment for acute asthma: can it be predicted or
      prevented?
AB  - We prospectively followed 314 children discharged from a children's hospital
      emergency department (ED) following an asthma attack, to identify risk, factors
      for relapse, i.e. a second ED visit for asthma within the next 10 days. Parents
      were surveyed concerning their child's past medical history, drugs received prior
      to the index visit, triggering factors, physician availability, parental anxiety,
      and sociodemographic variables. Data on severity of the attack, emergency
      treatment, response to treatment and drugs prescribed on discharge were extracted
      from the medical record. Ninety-six of the 314 children (31%) relapsed, most
      (68%) within 24 hours. Using multiple logistic regression, a predictive model was
      developed on 211 patients ("test sample"). The best model contained two
      variables: (1) the number of ED visits for acute asthma in the previous year
      (odds ratio [OR] = 2.4 for 4 or more vs fewer visits, 95% CI = 1.3-4.4) and (2)
      the intake of an oral short-acting theophylline preparation during the course of
      the acute treatment (OR = 0.4, 95% CI = 0.2-0.7). The sensitivity, specificity
      and positive predictive values of this model for predicting relapse were 73, 53,
      and 40%, respectively. When applied to a second randomly selected "validation
      sample" of 103 children, sensitivity was 73%, specificity 50%, and PPV 41%, thus
      indicating the stability of the model. The model identifies the number of ED
      visits in the previous year as an important risk factor for relapse. It also
      suggests that oral short-acting theophylline may still have a role in the
      treatment of patients in whom the contribution of inflammation to airway
      obstruction is minimal.

PMID- 8263567
TI  - Accuracy of the College Alumnus Physical Activity Questionnaire.
AB  - The validity and reproducibility of the Physical Activity Index from the College
      Alumnus Questionnaire (PAI-CAQ) were determined in 78 men and women (21-59 yr)
      with a broad range of physical activity habits. The PAI-CAQ was computed as the
      sum of energy expended in stair climbing, walking, and sports and recreational
      physical activity recalled from the past week. Data were validated against
      measures of cardiorespiratory fitness, body fatness, motion detection, and
      physical activity records. All physical activity was recorded by participants for
      six 48-hour periods. Each day of the week, including weekends, were represented
      at least twice in the physical activity records. Age-adjusted correlation
      coefficients between like activities on the College Alumnus Questionnaire and
      physical activity records ranged from 0.25 to 0.65 in men and 0.28 to 0.86 in
      women. Correlations between the PAI-CAQ and validation criteria that reflected
      total and heavy-intensity physical activities were higher (r = 0.34-0.69, p <
      0.05) than for lighter-intensity physical activities and motion detection
      expressed in MET-min.d-1 and kcal.d-1 (r < 0.35, p > 0.05). Test-retest
      reproducibility was higher over 1 month (r = 0.72) than over 8 and 9 months (r =
      0.34 and 0.43) (p < 0.05). Energy expended in walking and stair climbing was
      underestimated on the College Alumnus Questionnaire, resulting in lower PAI-CAQ
      scores, as compared to the physical activity records.

PMID- 8263568
TI  - HLA-A and -B antigens in chronic bronchitis.
AB  - The A- and B- types of Human Leucocyte Antigens (HLA) were examined in a group of
      Greek patients with a diagnosis of chronic bronchitis. The results were compared
      to those of 400 healthy unrelated controls (smokers and non-smokers) from the
      same population. A statistically significant increase of HLA-A1 and HLA-B17 was
      noted; a similar increase was also noted when only healthy smokers were utilized
      as a control group. These results support the hypothesis that genetic factors are
      also involved in the pathogenesis of this common disease.

PMID- 8263569
TI  - Cross-cultural adaptation of health-related quality of life measures: literature
      review and proposed guidelines.
AB  - Clinicians and researchers without a suitable health-related quality of life
      (HRQOL) measure in their own language have two choices: (1) to develop a new
      measure, or (2) to modify a measure previously validated in another language,
      known as a cross-cultural adaptation process. We propose a set of standardized
      guidelines for this process based on previous research in psychology and
      sociology and on published methodological frameworks. These guidelines include
      recommendations for obtaining semantic, idiomatic, experiential and conceptual
      equivalence in translation by using back-translation techniques and committee
      review, pre-testing techniques and re-examining the weight of scores. We applied
      these guidelines to 17 cross-cultural adaptation of HRQOL measures identified
      through a comprehensive literature review. The reporting standards varied across
      studies but agreement between raters in their ratings of the studies was
      substantial to almost perfect (weighted kappa = 0.66-0.93) suggesting that the
      guidelines are easy to apply. Further research is necessary in order to delineate
      essential versus optional steps in the adaptation process.

PMID- 8263570
TI  - Measuring quality of life in the frail elderly.
AB  - This study was carried out to develop and test the Geriatric Quality of Life
      Questionnaire (GQLQ), a health-related qualify of life (HRQL) questionnaire
      designed for the frail elderly. One hundred patients were asked to identify areas
      of their daily lives affected by their health. The GQLQ, developed on the basis
      of the results, the Rand Physical and Emotional Function Questionnaires, and the
      Barthel Index, were administered serially to a group of 76 patients participating
      in a randomized trial of a Geriatric Day Hospital. Participants in all phases of
      the study were over 65 years of age, living in their own home but with sufficient
      functional status impairment to compromise their ability to live independently.
      The GQLQ includes 25 questions focusing on activities of daily living (ADL),
      symptoms, and emotional function. In the ADL and Symptom domains respondents
      define personal problem areas. The responsiveness coefficients of the GQLQ ADL
      and Symptom domains (0.26 and 0.30 respectively) were similar to those of the
      Rand Physical Function instrument and the Barthel Index (0.29 and 0.20). The
      responsiveness coefficient of the GQLQ Emotional Function domain (0.50) was
      similar to that of the Rand Emotional Function instrument (0.63). Correlations
      between the GQLQ ADL domain and the Barthel Index (0.41), and between GQLQ and
      the Rand Physical Function instrument (0.30), were similar to the correlation
      between the Barthel Index and Rand Physical Function (0.40). While the GQLQ
      captures important areas of health-related quality of life impairment for the
      frail elderly, we failed to show any advantages in either responsiveness or
      validity to existing, simpler measures. New, specific instruments should be
      tested in head-to-head comparisons with existing measures, particularly generic
      instruments, before dissemination.

PMID- 8263571
TI  - Colon related symptoms in a 70-year-old Danish population.
AB  - The aim of the study was to assess (1) the prevalence of colon related symptoms
      among the elderly and (2) whether different definitions identify different
      subjects with Irritable Bowel Syndrome. The study was carried out in a random
      sample of 1119 70-year-old Danes of whom 72% answered a questionnaire concerning
      colon related symptoms. The number of bowel movements a week ranged from 0 to 21
      among men and 1 to 28 among women, 5% limits were at < 3 or > 15 movements a
      week. The individual symptoms occurred with prevalences between 16 and 25% among
      men and 27 and 41% among the women. Abdominal pain, distension and borborygmi
      occurred significantly more often among women than men, whereas no sex difference
      was found for alternating stool consistency and number of bowel movements.
      According to the different definitions the prevalence of Irritable Bowel Syndrome
      varied from 0 to 18% among men and 4 to 32% among women. The subpopulations with
      Irritable Bowel Syndrome identified by various definitions had less than half of
      the subjects in common.

PMID- 8263572
TI  - Descriptive epidemiology of idiopathic dilated cardiomyopathy in Washington
      County, Maryland, 1975-1991.
AB  - Estimates of the incidence of idiopathic dilated cardiomyopathy (IDC) were
      obtained by identifying cases from Washington County, Maryland who were
      hospitalized at local and regional hospitals over a recent 17 year period. All of
      the verified cases had evidence of ventricular dilatation and hypokinesis, with a
      left ventricular ejection fraction of less than 40%. A total of 26 cases were
      hospitalized over the period 1975-1991. The average age of the cases at the time
      of diagnosis was 55.5 years (range 22-80 years of age). About 58% of the subjects
      were males. A marked increase in newly diagnosed cases of IDC occurred in this
      population in recent years; 38% of the cases (10 of 26) were newly diagnosed
      during 1991 alone. Over the period 1975-1991, the average annual incidence rate
      of hospitalized cases was 1.6 per 100,000 among men and 1.2 per 100,000 among
      women. During the last 7 years of the case ascertainment period (1985-1991), the
      average annual incidence rate was 3.5 per 100,000 among men and 2.5 per 100,000
      among women. These results provide additional evidence that IDC is being
      increasingly recognized by clinicians, and underscore the need for an improved
      understanding of the distribution and determinants of this often fatal condition.

PMID- 8263573
TI  - Recall bias in the association of micronutrient intake and breast cancer.
AB  - A nested case-control study within the Canadian National Breast Screening Study
      was conducted to examine whether there was evidence for recall bias in the
      reporting of past micronutrient intake. Dietary data collected upon enrollment
      between 1982 and 1985 from 325 breast cancer cases and 628 matched controls were
      compared with data collected in 1988 after disease diagnosis. The retrospective
      estimates of mean micronutrient intakes from food sources were found to be very
      similar to the prospective estimates for cases and controls. Errors of omission
      and commission for the reporting of previous supplementary vitamin use were
      identical for both subject groups. The odds ratios estimated for the association
      of micronutrient intake and breast cancer for the prospective and retrospective
      data were similar in magnitude and the 95% confidence intervals overlapped
      considerably. There was no evidence for recall bias in the estimation of past
      micronutrient intake by breast cancer cases as compared to controls.

PMID- 8263574
TI  - The validity of health assessments: resolving some recent differences.
AB  - The purpose of this paper is to examine what is meant by a valid measure of
      health. Guyatt, Kirshner and Jaeschke propose that health tests should be
      designed so as to have one of several kinds of validity: "longitudinal construct
      validity" for those which are used for longitudinal research designs, and "cross
      sectional construct validity" for those which are used for cross-sectional
      designs. Williams and Naylor argue that this approach to test classification and
      validation confuses what a test purports to measure with the purpose for which it
      is used, and that some tests have multiple uses. A review of the meanings of
      validity in the psychological test literature shows that both sets of authors use
      the term validity in an idiosyncratic way. Although the use of a test (evaluated
      by content validity) should not be conflated with whether the test actually
      measures a specified construct (evaluated by construct validity), if health is
      actually made up of several constructs (as suggested in Hyland's interactional
      model) then there may be an association between types of construct and types of
      purpose. Evidence is reviewed that people make several, independent judgements
      about their health: cognitive perceptions of health problems are likely to be
      more sensitive to change in a longitudinal research design, whereas emotional
      evaluations of health provide less bias in cross-sectional designs. Thus, a
      classification of health measures in terms of the purpose of the test may
      parallel a classification in terms of what tests purport to measure.

PMID- 8263575
TI  - Comparison of eligible randomized patients with two groups of ineligible
      patients: can the results of the VA Total Parenteral Nutrition clinical trial be
      generalized?
AB  - The recently reported VA Cooperative Study "A Randomized Clinical Trial of Total
      Parenteral Nutrition (TPN) in Malnourished Surgical Patients" randomized 395 pre
      operative patients to TPN treatment or control. The study concluded that the use
      of perioperative TPN should be limited to the most severely malnourished
      patients. The study also followed 233 patients eligible for the study who refused
      to give informed consent for randomization (Eligible Refusers) as well as 1220
      patients who were ineligible because they were not sufficiently malnourished
      (Index Group). Patients in the Index Group were determined to be significantly
      healthier than those in the two eligible groups of patients. Those in the
      Eligible Refuser group were shown to be slightly less malnourished than the
      Randomized Patients. The 395 patients randomized to the study (Randomized
      Patients) showed the highest rate of septic complications at 30 days and at 90
      days (10% and 13% respectively) with rates for the Eligible Refusers slightly
      lower (8% and 9%) and Index Group rates still lower (4% and 4%). Nonseptic
      complication rates showed the same pattern (19% and 22% for the Randomized group,
      12% and 12% for Eligible Refusers, and 10% and 10% for the Index Group). Because
      (a) the beneficial effect of TPN is attained only in severely malnourished
      patients, (b) there is increased risk of septic complications with TPN use in
      patients not severely malnourished, (c) Index Group patients, and presumably the
      population of patients from which they are drawn, are not severely malnourished,
      it follows that unless specifically indicated, TPN should not be used in
      nonseverely malnourished patients.

PMID- 8263576
TI  - Inconsistency of a model aimed at predicting bacteremia in hospitalized patients.
AB  - Clinical prediction rules can help physicians determine the necessity for blood
      cultures in specific patients and/or in whom empiric antibiotic treatment should
      be administered. Before adopting a prediction rule its validity must be evaluated
      in different settings. We revealed independent predictors of true bacteremia and
      developed a risk score based on them in one group of adult hospitalized patients
      (n = 474; derivation set). An attempt was made to validate this risk score in a
      second group of in-patients at the same hospital (n = 438; validation set). The
      derivation set included 540 blood culture episodes and the validation set 516. A
      blood culture episode was defined as one or more of all blood specimens withdrawn
      for culture from one patient over one 24 hour period. Independent multivariate
      predictors of true bacteremia were: temperature of 39 degrees C or higher,
      current immunosuppressive therapy, serum alkaline phosphatase > 100 IU and
      hospitalization in an intensive care unit. In the low risk group, defined by the
      absence of the said predictors, the rates of true bacteremia were 5.1 and 4.6%
      for the derivation and validation sets, respectively. As raised temperature is
      the main clinical feature guiding physicians to suspect bacteremia, we examined
      the probability of true bacteremia in patients with a temperature of less than 38
      degrees C and found it to be 5.6% in the two sets. The model identified high risk
      subset patient groups demonstrating true bacteremia in 38% of all episodes in the
      derivation set and the comparatively low rate of 12.1% (p < 0.01) for the
      validation set.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263577
TI  - Differential rates of relapse in subgroups of male and female smokers.
AB  - Subjects for this study were 265 participants of stop-smoking clinics (mean age =
      42.6 years; average number of cigarettes smoked daily = 26.0) who were examined
      before and immediately after cessation and then followed for 1 year. The
      objective of this study was to identify subgroups of smokers with different rates
      of relapse using tree-structured survival analysis, a multivariate approach to
      classification. Five distinct subgroups that differed with respect to the rate of
      relapse were identified: (I) subjects (n = 15) with very low precessation
      cotinine levels (< or = 129 ng/ml), who had an exceptionally low rate of relapse
      (mean abstinence time = 270 days); (II) women 32 years old and younger (n = 24),
      who had a very high rate of relapse (mean abstinence time = 30.5 days); (III)
      women over 32 years old (n = 121), with the next highest rate of relapse (mean
      abstinence time = 98.9 days); (IV) men 36 years old and younger (n = 31), who had
      a mean abstinence time of 196.7 days; and (V) men over 36 years old (n = 74), who
      abstained an average of 130.2 days before relapsing. Relapse curves for all
      groups (except III vs V) differed significantly from each other, p < 0.05.
      Results indicate that this approach can identify interactions among individual
      differences that are variably associated with relapse rates. Identification of
      relapse subgroups may have important implications for both theories and treatment
      of smoking relapse.

PMID- 8263578
TI  - The analysis of ordinal agreement data: beyond weighted kappa.
AB  - The weighted kappa statistic has been used as an agreement index for ordinal
      data. Using data on the comparability of primary and proxy respondent reports of
      alcohol drinking frequency we show that the value of weighted kappa can be
      sensitive to the choice of weights. The distinction between association and
      agreement is clarified and it is shown that in some respects weighted kappa
      behaves more like a measure of association than an index of agreement. In
      particular, it is demonstrated that the weighted kappa statistic is not always
      sensitive to differences in the observed proportion in exact agreement and that
      high values of weighted kappa can be observed even when the level of agreement is
      low. We illustrate the use of statistical models in the analysis of epidemiologic
      agreement data and conclude that modelling ordinal agreement data produces
      insights which cannot be obtained through the use of weighted kappa statistics.

PMID- 8263579
TI  - Reinterpreting mortality statistics: some uses of Gompertzian analysis in
      epidemiological research.
AB  - Gompertzian analyses of mortality data have recently been undertaken for a number
      of individual conditions (Riggs JE. Mech Ageing Dev 1990; 55: 207-220 [1];
      Neilson S et al. Mech Ageing Dev 1992; 64: 201-216 [2]; Neilson S et al. Acta
      Neurol Scand 1993; 87: 184-191 [3]). Such analyses are in principle of particular
      epidemiological value in circumstances where demographic change is occurring and
      where the balance between mortality from different conditions is subject to
      change. However, the extent to which a Gompertzian relationship between age and
      mortality holds for particular conditions has been subject to debate. In this
      analysis it is demonstrated that even some conditions which do not superficially
      hold to a Gompertz relationship do in fact do so, if such conditions are
      considered to be restricted to small, inherently susceptible subpopulations. By
      analysing mortality from a range of neurological conditions within the context of
      general mortality in England and Wales, conditions with different aetiologies
      such as Huntington's chorea, amyotrophic lateral sclerosis and multiple sclerosis
      can be shown to have a Gompertzian mortality rate distribution. Such analyses are
      of substantial value in indicating how demographic change affects the balance of
      mortality between conditions, as well as directing interest to revised
      aetiological possibilities.

PMID- 8263580
TI  - Pride and prejudice: the case of streptococcal pharyngitis and the WBC.

PMID- 8263581
TI  - Randomized discontinuation trials: utility and efficiency.
AB  - The randomized discontinuation trial (RDT) is a two-phase trial. In phase I all
      patients are openly treated with the medication being evaluated. In phase II,
      those who have responded are randomly assigned to continue the same treatment or
      switch to placebo. Usually, non-compliers and "adverse reactors" identified in
      phase I are excluded from phase II. To investigate the value of this design, we
      reviewed the advantages and limitations of discontinuation studies, and compared
      the RDT design to the classic randomized clinical trial design in terms of
      clinical utility and efficiency (sample size). A computer model was used to study
      the efficiency of the two designs under a broad range of assumptions. The RDT
      design is particularly useful in studying the effect of long-term, non-curative
      therapies, especially when the clinically important effect is relatively small,
      and the use of placebo should be minimized for ethical or feasibility reasons.
      However, its use is limited if the objective of an investigation is to estimate
      the magnitude of absolute treatment effects and toxic effects in the source
      population, or to evaluate a potentially curative treatment. Our results indicate
      that selecting responders prior to randomization has a very strong effect on the
      relative efficiency of the trial. Further improvement may be achieved by
      excluding non-compliers and adverse reactors. Under the assumptions tested in our
      model, the sample size required in phase II of an RDT was only 20-50% of that in
      a classic trial.

PMID- 8263582
TI  - Variations in the risk of breast cancer associated with a family history of
      breast cancer according to age at onset and reproductive factors.
AB  - In a case-control study of 495 breast cancer patients and 785 controls between 20
      and 56 years of age, the risk of breast cancer associated with a family history
      of breast cancer was studied according to age and reproductive factors. The
      familial risk of breast cancer was not significantly modified by age at onset,
      age at menarche, number of children, age at first full-term pregnancy, menstrual
      cycle length or age at menopause. However, the familial risk significantly
      increased with the number of abortions (p < 0.05) and seemed to decrease after a
      natural menopause (p = 0.08). These results suggest that a familial
      predisposition to breast cancer exerts the same influence during the first six
      decades of life, except maybe when there are isolated or repeated events such as
      abortions or artificially imposed menopause, in which case the risk is apparently
      greater.

PMID- 8263583
TI  - Maternal employment, maternal care and pediatric visits for minor acute
      illnesses.
AB  - The purpose of these analyses, based on a prospective follow-up of 532 children,
      was to describe reported use of three maternal care actions for minor illness
      episodes, and to determine if maternal employment, as well as other
      sociodemographic factors, were associated with maternal care behaviors prior to
      each child's first pediatric acute-care visit. Two factors were associated with
      greater use of maternal care prior to an illness episode: the mother not working
      outside the home and less satisfaction with medical care. These results are
      consistent with the hypothesis that employed women with child-care arrangements
      are more likely than are other women to seek medical care for symptoms that are
      minor and can be managed with family-initiated care.

PMID- 8263584
TI  - An index of scientific quality for health reports in the lay press.
AB  - Although the quality of health reporting has been criticized for being
      unscientific, evaluations of health care reporting have been limited by the lack
      of a reliable and credible measure of scientific quality. We developed an index
      of scientific quality (ISQ) for health-related news reports and tested its
      reliability and sensibility. Items were generated from a survey of the literature
      and experts in research methodology. Items that were unclear, confusing or
      discriminated poorly between articles of high and low scientific quality were
      revised or deleted in an iterative process wherein potential criteria were
      independently applied to samples of 5 to 15 articles by 6 raters. To test the
      reliability of the final criteria 60 articles were drawn from three sampling
      frames: newspapers, magazines, and professional journals. Articles were
      intentionally selected to obtain a wide range of quality and topics. Two
      categories of raters were used: research assistants and physicians with research
      training. All 6 raters assessed all 60 articles. The sensibility of the index was
      tested by a questionnaire with 13 items related to face validity and content
      validity as well as other aspects of sensibility. The questionnaire was completed
      by 20 researchers and 13 health and science writers. The final ISQ includes 7
      items that address the extent to which a report allows readers to draw
      conclusions about the applicability, validity and practical importance of the
      information that is reported. Chance corrected agreement (kappa) among all 6
      raters for overall scientific quality was 0.62 (SE 0.02). The index was found to
      be sensible with only one major problem, the need for judgment in making ratings.
      While some degree of subjectivity appears to be inevitable in rating the
      scientific quality of health reports, the ISQ is acceptable reliable and credible
      and should be useful for evaluating and improving the scientific quality of
      health reporting.

PMID- 8263585
TI  - A pain-free death.

PMID- 8263586
TI  - Moral and ethical issues.

PMID- 8263587
TI  - Staff development for culturally sensitive nursing care.
AB  - This article describes a workshop conducted to address the need to incorporate
      cultural sensitivity into nursing care. Three major points are explained: (a) how
      ethnicity and culture of patients affect health care attitudes, values, and
      practices; (b) how knowledge of cultural characteristics can improve nursing and
      health care effectiveness; and (3) the cultural awareness strategies generated by
      those who participated in the workshop.

PMID- 8263588
TI  - Train-the-trainer for hospital-wide safety training.
AB  - This article describes a hospital-wide safety program that was developed using
      the train-the-trainer model. Education specialists worked with hospital safety
      experts to develop a program that met Joint Commission on Accreditation of
      Healthcare Organization standards, improved the quality and safety of the
      hospital environment, and strengthened interdepartmental relationships. A variety
      of outcome measures, including quality assurance indicators, was used to evaluate
      the program.

PMID- 8263589
TI  - An adventure in scientific inquiry: the development of a hospital-based nursing
      research committee.
AB  - Research is becoming a responsibility in staff development educators' already
      diverse and extensive repertoire. Recognition as a specialty has required the
      staff development educator to serve as a role model in nursing research and its
      applicability to practice. In this article, the authors delineate a step-by-step
      approach to developing a hospital-based nursing research committee. The intent is
      to provide a broad design as well as specific details needed to facilitate the
      committee's viability and longevity.

PMID- 8263590
TI  - Games in nursing staff development.
AB  - Adult learners have different learning styles and needs. To facilitate learning
      in a mixed group, various strategies must be used. Games have proven to be
      effective in basic and continuing nursing education. Educational games are
      gaining popularity in nursing staff development. This article discusses games in
      nursing staff development.

PMID- 8263591
TI  - Evaluation of a patient information booklet.
AB  - Preoperative teaching is an integral component of the care surgical patients
      receive. The need for consistent preoperative information has resulted in growing
      use of printed health information. There are many printed materials for nurses to
      choose from; however, these materials serve no useful teaching purpose if
      patients are unable to understand them. This study evaluates how well surgical
      patients understand the content presented in an educational booklet used for
      preoperative teaching. A Cloze test was designed to assess comprehension of a
      booklet prepared at a grade five reading level. Scores revealed that 84% of
      subjects scored above 56% and were able to comprehend the material independently;
      10% scored between 44% and 56%, indicating they would require some help; and 6%
      scored less than 44% and were not able to comprehend the information.

PMID- 8263592
TI  - A three tier competency program.
AB  - One of the complex problems facing nurse administrators and staff development
      educators is providing a mechanism to ensure competency of the nursing staff in
      specialty areas of practice. At the Santa Clara Valley Medical Center in San
      Jose, California, a staff nurse devised a program to solve this problem. One of
      the benefits of the program was to increase nurse retention and decrease turnover
      in a busy urban hospital.

PMID- 8263593
TI  - Team teaching on the evening and night shifts.

PMID- 8263594
TI  - A computer-assisted independent study.

PMID- 8263595
TI  - Challenge to nurse educators: a synthesis of practice and research.

PMID- 8263596
TI  - Arnold Edward Schaefer (1917-1992).

PMID- 8263597
TI  - A diet enriched in monounsaturated fats decreases low density lipoprotein
      concentrations in cynomolgus monkeys by a different mechanism than does a diet
      enriched in polyunsaturated fats.
AB  - To determine the mechanisms whereby dietary fat saturation influences LDL
      cholesterol and apolipoprotein B concentrations, 10 cynomolgus monkeys were fed
      each of three experimental diets enriched in saturated, monounsaturated or
      polyunsaturated fatty acids in a crossover design consisting of three 13-wk
      periods. Each diet contained 30% of energy as fat with 0.05 mg cholesterol/kJ and
      differed solely by the isocaloric substitution of fatty acids as 60% of total fat
      energy. The replacement of dietary saturated fatty acids with either mono- or
      polyunsaturated fatty acids resulted in significant reductions of plasma total
      cholesterol (-17% and -30%, respectively), HDL cholesterol (-32% and -41%,
      respectively), apoA-1 (-37% and -44%, respectively), and apolipoprotein B (-28%
      and -36%, respectively) concentrations. Additionally, when dietary
      polyunsaturated fatty acids were substituted for saturated fatty acids, a 27%
      reduction in VLDL + LDL cholesterol was significant. Metabolic experiments
      suggested that the significantly reduced concentrations of apolipoprotein B
      observed during the monounsaturated and polyunsaturated fatty acid phases
      relative to the saturated fatty acid phase could not be entirely explained by
      changes in LDL apolipoprotein B clearance but rather were likely due to decreased
      LDL apolipoprotein B production rates. However, enhanced LDL apolipoprotein B
      catabolism accounted for the even greater reductions in VLDL + LDL cholesterol
      and apolipoprotein B concentrations observed during the polyunsaturated fatty
      acid phase vs. the monounsaturated fatty acid phase. Our data suggest that
      monounsaturated and polyunsaturated fatty acids lower apolipoprotein B
      concentrations by distinct mechanisms, with polyunsaturated fatty acids affecting
      LDL apolipoprotein B catabolism as well as production.

PMID- 8263598
TI  - Starches of varied digestibilities differentially modify intestinal function in
      rats.
AB  - Starches of different digestibilities may enter the colon to different extents
      and alter colonic function. Male Fischer 344 rats were fed diets containing 25%
      cooked potato starch, arrowroot starch, high amylose cornstarch or raw potato
      starch for 6 wk. Fecal weight, transit time, colonic thymidine kinase activity (a
      marker for cell proliferation), and weight, starch content and pH of the cecum
      and proximal and distal colon were measured. Raw potato starch was much less
      completely digested than high amylose cornstarch, resulting in a 32-fold greater
      amount of undigested starch entering the cecum in the raw potato starch group.
      Both the high amylose cornstarch and raw potato starch diets significantly
      enhanced fecal weight and produced large intestinal hypertrophy, effects that
      were greatest in the raw potato starch group. Raw potato starch feeding was
      associated with the highest level of thymidine kinase activity, although the
      differences in thymidine kinase activity among the four groups were not
      significant. This diet also produced a 50% longer transit time. Entry of a large
      amount of raw potato starch into the colon resulted in greater luminal acidity,
      greater luminal bulk and slower transit. A much smaller amount of starch entered
      the colon in the high amylose cornstarch group and resulted in fecal bulking but
      no alteration in transit.

PMID- 8263599
TI  - Dietary fish oil supplementation attenuates myocardial dysfunction and injury
      caused by global ischemia and reperfusion in isolated rat hearts.
AB  - To determine the effect of dietary fish oil supplementation on myocardial
      dysfunction following ischemia-reperfusion, independent of plasma and blood
      cells, Sprague-Dawley rats were fed fish oil-rich nonpurified diet or butter
      enriched diet for 5 d. Myocardial content of long-chain and (n-3) polyunsaturated
      fatty acids was greater in the fish oil-fed rats (P < 0.01), whereas (n-6) fatty
      acid content was lower compared with controls (P < 0.01). Platelet aggregation in
      fish oil-fed rats was also inhibited. Hearts from all rats were subjected to 15
      min of global ischemia and 10 min of reperfusion. In hearts of control rats,
      ischemia-reperfusion resulted in a marked decrease in force of cardiac
      contraction, increase in coronary perfusion pressure, appearance of ventricular
      arrhythmias and release of creatine kinase and thromboxane B2 in the coronary
      effluent. Dietary fish oil supplementation attenuated myocardial dysfunction
      induced by ischemia-reperfusion, as indicated by smaller change in force of
      cardiac contraction (-77% vs. -89%, P < 0.05) and coronary perfusion pressure
      (+37% vs. +71%, P < 0.001). Concomitantly, release of creatine kinase as well as
      thromboxane B2 in coronary effluent was lower (P < 0.01). Ventricular arrhythmias
      occurred less frequently in hearts from fish oil-fed rats. Thus, short-term
      dietary fish oil supplementation attenuates myocardial dysfunction caused by
      ischemia-reperfusion by a direct effect on the heart independent of blood and
      plasma components.

PMID- 8263600
TI  - UDP glucuronosyltransferase gene expression is involved in the stimulation of
      ascorbic acid biosynthesis by xenobiotics in rats.
AB  - Wistar-Shi (genotype +/+), heterozygous Gunn (j/+) and homozygous Gunn (j/j) rats
      was injected intraperitoneally with 3-methylcholanthrene (3MC) dissolved in corn
      oil. In rats of all genotypes the hepatic concentration of UDP
      glucuronosyltransferase (UDPGT) mRNA was increased at 48 and 96 h after the
      treatment with 3MC. Hepatic activity of 4-nitrophenol UDPGT was increased by 3MC
      in Wistar-Shi rats and heterozygous Gunn rats but not in homozygous Gunn rats.
      Urinary ascorbic acid excretion increased 72 and 96 h after the injection with
      3MC in Wistar-Shi and heterozygous Gunn rats but not in homozygous Gunn rats.
      Ninety-six hours after the injection with 3MC, the hepatic concentration of
      ascorbic acid in Wistar-Shi rats was 90% higher than that in the corresponding
      control group, whereas in heterozygous and homozygous Gunn rats the increases
      were 70 and 30%, respectively. Wistar-Shi rats and homozygous Gunn rats were also
      injected daily for 3 d with sodium phenobarbital. In rats of both genotypes, the
      activity and hepatic concentration of chloramphenicol-UDPGT mRNA and liver and
      urine ascorbic acid concentration were increased by sodium phenobarbital. The
      data indicate that the stimulation of the expression of both the 4-nitrophenol
      and chloramphenicol UDPGT genes plays a key role in the ascorbic acid
      biosynthesis induced by 3MC and sodium phenobarbital.

PMID- 8263601
TI  - Dietary fish oil does not alter glucose tolerance in conscious rats.
AB  - We examined the effect of dietary fish oil (MaxEPA) and sunflower seed oil on
      glucose tolerance in male Wistar rats. Semipurified diets containing 100 g oil/kg
      diet were administered for 30 d. The fish oil diet contained 26 g (n-3) fatty
      acids, 16 g eicosapentaenoic acid and 10.4 g docosahexaenoic acid/kg diet.
      Phospholipids from liver, pancreas, and pancreatic islets were enriched in
      eicosapentaenoic and docosahexaenoic acids by the fish oil diet. In unfed
      pentobarbital-anesthetized rats, both basal plasma insulin concentration and
      insulin responses to intravenous glucose were significantly lower for fish oil
      fed rats although glucose responses were similar; however, incremental excursions
      in plasma insulin over the basal concentrations did not differ. Intravenous
      glucose tolerance was also examined in conscious unfed rats under minimal
      restraint. Responses of plasma glucose and insulin were similar for fish oil- and
      sunflower oil-fed groups. Furthermore, in another experiment, intravenous glucose
      tolerance tests were similar for conscious rats provided with either 100 g fish
      oil or corn oil/kg nonpurified diet. Thus, glucose-induced insulin secretion is
      lower in rats fed fish oil than in rats fed sunflower oil, when tests are
      conducted in pentobarbital-anesthetized animals but not when tests are performed
      in conscious rats; there was no effect on plasma glucose in either anesthetized
      or nonanesthetized rats. Therefore, substitution of (n-3) for (n-6)
      polyunsaturated fatty acids in tissue phospholipids does not alter plasma glucose
      or insulin in conscious male Wistar rats.

PMID- 8263602
TI  - Deficiency of (n-6) but not (n-3) polyunsaturated fatty acids inhibits the
      secretagogue effect of prolactin in lactating rat mammary epithelial cells.
AB  - The repercussions of various kinds of dietary polyunsaturated fatty acid (PUFA)
      deficiencies on the fatty acid composition of membranes and on the secretory
      activity of lactating female rat mammary epithelial cells were investigated.
      Primiparous female rats were fed different PUFA diets from weaning: adequate (n
      6) and (n-3) PUFA supply; overall PUFA deficiency; specific (n-6) PUFA deficiency
      or specific (n-3) PUFA deficiency. Mammary gland phospholipids contained very low
      amount of (n-3) PUFA in control rats, and only 1% docosahexaenoic acid. The fatty
      acid composition of membrane phospholipids reflected the type of diet received by
      the animals, i.e., the diets deficient in the (n-3) or (n-6) PUFA series resulted
      in lower (n-3) or (n-6) PUFA, and the (n-3) + (n-6) deficient diet caused a true
      overall PUFA deficiency in the membranes. The morphology of cells from overall
      PUFA- or (n-6) PUFA-deficient rats showed an accumulation of secretory vesicles
      in the cytoplasm. Basal casein secretion was independent of the diet and of the
      composition of membrane phospholipids. However, prolactin did not have a
      secretagogue effect on cells from (n-6) PUFA- or overall PUFA-deficient rats but
      retained this effect on cells from (n-3)-deficient rats. These results emphasize
      the specific role of (n-6) PUFA in the functioning of the lactating mammary
      epithelial cell.

PMID- 8263603
TI  - Dietary biotin deficiency affects reproductive function and prenatal development
      in hamsters.
AB  - The effects of maternal dietary biotin deficiency on hamster embryos were
      examined by adding different amounts of avidin (0, 10, 50, 100 or 1000 mg/kg
      diet) to a semipurified commercial diet during the entire period of gestation. On
      d 10 of gestation, reduced dietary biotin resulted in a high incidence of
      resorbed and dead embryos. In addition, both the crown-rump length and head
      length of dietary biotin-deficient embryos were lower, and their digit
      development was retarded. These embryos were characterized by pericardial cavity
      enlargement (40%) and zig-zag closure line of the neural tube (44%). Some embryos
      exhibited abnormalities of the craniofacial region and tail. On d 14 of
      gestation, embryonic growth retardation, morphological abnormalities and skeletal
      defects were seen in the dietary biotin-deficient group (fed 100 mg avidin/kg
      diet). The striking abnormalities were cleft palate, micromelia, micrognathia and
      rib deformities in approximately 10% of the fetuses. Histological examination of
      the placentae revealed some differences in the spongiotrophoblast and labyrinth
      layers between the control and dietary biotin-deficient groups. The teratogenic
      effect of dietary biotin deficiency previously observed in mice was confirmed in
      hamsters.

PMID- 8263604
TI  - Dietary fatty acid composition influences energy accretion in rats.
AB  - To study the influence of dietary fatty acid composition on energy metabolism,
      forty male rats were fed elemental diets containing 42% of energy as fish oil,
      safflower oil, olive oil or beef tallow for 12 wk. Food intakes and body weights
      were measured daily. Energy expenditure and body composition were determined
      using doubly labeled water on the final 2 d. Pooled fecal energy losses differed
      in response to dietary manipulation, with losses greatest in rats fed beef tallow
      and least in those fed olive oil. Higher lean body mass gains and lower fat mass
      gains were observed in rats fed diets containing fish oil, compared with rats fed
      olive oil or beef tallow. Total energy gains in rats fed olive oil (3632 +/- 145
      kJ) and beef tallow (3850 +/- 136 kJ) were higher than those in rats fed fish oil
      (2905 +/- 196 kJ). Energy efficiency in both the olive oil and beef tallow groups
      was also higher than that in the fish oil group. There were no differences in
      energy expenditure measured by doubly labeled water technique among the four
      groups. The data suggest that dietary fatty acid composition alters the
      efficiency of energy substrate accretion in rats.

PMID- 8263605
TI  - Risk factors associated with xerophthalmia in northern Sudan.
AB  - The prevalence of eye signs and symptoms of vitamin A deficiency was determined
      among 29,615 Sudanese children between 6 and 72 mo of age, in five rural areas of
      Khartoum and Gezira provinces. Of all children, 2.9% were vitamin A deficient,
      and of these > 90% had Bitot's spots. Bivariate associations were found between
      xerophthalmia and the rural councils where the children lived, household wealth,
      consumption of vitamin A-containing foods, child sex, child age and weight-for
      height Z-scores. Multivariate analysis showed that the following factors made
      significant independent contributions to the risk of xerophthalmia: living in
      remote and arid regions, male gender, age, poverty of the household, and
      prevalence of diarrhea. On the other hand, less xerophthalmia was observed among
      children who during the 24 h preceding the survey had consumed dairy products or
      non-leafy vegetables containing vitamin A. Intervention programs aimed at
      increasing household income and promoting consumption of foods containing vitamin
      A should contribute to the reduction of vitamin A deficiency among Sudanese
      children.

PMID- 8263606
TI  - High fiber diets slow bone turnover in young men but have no effect on efficiency
      of intestinal calcium absorption.
AB  - Dietary fiber reduces the absorption of dietary calcium from a meal, but its
      impact on calcium kinetics is unknown. We therefore evaluated the effects of a
      high fiber diet on calcium balance and kinetics and on calcium-regulating
      hormones. Seven young men each participated in two 23-d experiments. In the low
      fiber period the controlled diet provided 6.5 g fiber/d and 530 mg calcium/d. In
      the high fiber period fiber was increased to 31.3 g/d and calcium to 586 mg/d by
      substituting high fiber cereal. Measured between d 7 and 12 of each period, the
      high fiber diet significantly lowered the apparent absorption of calcium (from
      60.6 +/- 23.8% to 37.1 +/- 26.5%) and reduced calcium balance, although balance
      remained positive overall. Fiber had no effect on serum total or ultrafiltrable
      calcium, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D or parathyroid hormone
      concentrations measured on d 1, 7, 12 and 20. Calcium kinetics was studied
      between d 17 and 23 by administering oral 44Ca and intravenous 42Ca to fasting
      subjects. Fractional absorption of calcium in the fasting state was unaffected by
      fiber. However, during the high fiber period, subjects had significantly lower
      bone accretion, resorption and turnover rates, and calcium flow to bone from the
      exchangeable pool than during the low fiber period. We conclude that the fiber
      induced reduction in calcium absorption slowed down bone calcium turnover but did
      not increase the efficiency of intestinal absorption.

PMID- 8263607
TI  - A noninvasive method for measuring urea kinetics with a single dose of
      [15N15N]urea in free-living humans.
AB  - A noninvasive method is described in which the endogenous rate of urea production
      can be determined in normal, free-living adults. A single dose of [15N15N]urea
      was given orally, and the amount of label excreted as [15N15N]urea and
      [15N14N]urea in urine over the subsequent 48 h was measured. From the rates of
      excretion of labeled and unlabeled urea the rate of urea production was derived.
      Using this single-dose protocol the rate of urea production was 207 +/- 56 (mean
      +/- SD) mg N/(kg.d) in six normal adult men consuming 74 g protein/d. These
      results were not different when compared with rates of urea production obtained
      with a prime/intermittent protocol in an earlier study in the same individuals
      [199 +/- 20 mg N/(kg.d)]. We conclude that urea kinetics can be measured
      noninvasively with a single dose of [15N15N]urea and that this method may be
      suitable for use in free-living individuals to determine urea production rates
      for habitual dietary intakes.

PMID- 8263608
TI  - Vitamin B-6 status indices are lower in pregnant than in nonpregnant women but
      urinary excretion of 4-pyridoxic acid does not differ.
AB  - The cause of reduced plasma pyridoxal-5'-phosphate (PLP) concentration and the
      validity of plasma PLP concentration as a vitamin B-6 status indicator during
      pregnancy are not well understood. In this study, pregnant and nonpregnant women
      consumed a controlled diet for 5 d to exclude dietary intake as a factor in
      altered vitamin B-6 metabolic utilization. Plasma PLP and pyridoxal (PL)
      concentrations were significantly lower and higher, respectively, and plasma
      PL+PLP concentration was significantly lower during pregnancy. When plasma PLP
      and PL concentrations were normalized based on plasma albumin concentration, the
      differences were less marked but were still significant. The erythrocyte
      aspartate aminotransferase activity coefficient was significantly greater in
      pregnant women which is a further indication of reduced vitamin B-6
      concentrations in the blood. No difference was observed in the urinary excretion
      of 4-pyridoxic acid between the pregnant and nonpregnant women. Results of this
      study demonstrate that vitamin B-6 status indices are lower during pregnancy
      without differences in the urinary excretion of 4-pyridoxic acid.

PMID- 8263609
TI  - Resistant starch decreases serum total cholesterol and triacylglycerol
      concentrations in rats.
AB  - Rats were meal-fed semipurified diets containing a low (0.8 g/MJ) and a high (9.6
      g/MJ) amount of resistant starch (RS) or various amounts of RS (0.8 to 9.6 g/MJ)
      and guar gum (0 to 8.8 g/MJ). In one experiment, rats were fed the low and high
      RS diets in three dietary regimens (ad libitum consuming, 12 h ad libitum/12 h
      food deprived, and meal fed). Effects of RS and guar gum on serum postprandial
      and postabsorptive concentrations of total cholesterol (TC) and triacylglycerol
      (TAG), growth, hydrogen excretion, tissue weights and contents of small intestine
      and cecum, and pH of cecal contents were investigated. In addition, effects of RS
      on food intake, de novo hepatic synthesis of fatty acids and neutral sterols, and
      on lipoprotein lipase activity and weight of epididymal fat pads were
      investigated. Compared with feeding the low RS diet, the high RS diet reduced the
      serum TC and TAG concentrations, with these effects observed after 1 and 2 wk of
      feeding, respectively. The dietary regimen did not influence the effect of RS on
      the serum TC and TAG concentrations, but it did affect the serum TAG
      concentration. Resistant starch had no effect on the hepatic synthesis of fatty
      acids and neutral sterols or on the lipoprotein lipase activity in epididymal fat
      pads. Guar gum also reduced the serum TC concentration, but it had no effect on
      serum TAG concentration. The tissue weights and contents of small intestine and
      cecum as well as hydrogen excretion increased with increasing amounts of dietary
      RS and guar gum, whereas the pH of cecal contents decreased. No effects of RS on
      food intake and total body weight gain were found, whereas guar gum decreased
      weight gain. Feeding the high RS diet also led to a lower weight of the
      epididymal fat pads. We conclude that dietary RS can reduce serum TC and TAG
      concentrations and fat accretion.

PMID- 8263610
TI  - Feeding status affects glucose metabolism in exercising horses.
AB  - Four standardbred horses were used in a Latin square design experiment to
      evaluate the effects of feeding status on metabolic response to exercise. Horses
      were deprived of food overnight and then fed 0 (control condition), 1, 2 or 3 kg
      of corn grain approximately 2.5-3 h before exercise. The exercise test consisted
      of a warm-up phase (heart rate mean = 144 beats/min) followed by 800 m of walking
      and then a high intensity work bout for 1600 m (heart rate mean = 206 beats/min).
      All tests were conducted on a high speed equine treadmill on which the horses had
      been previously conditioned. During exercise, the control treatment resulted in
      steady plasma glucose concentrations, whereas all other treatments (1, 2 or 3 kg
      corn) caused a decline in plasma glucose. Liver glycogen concentration was
      decreased by exercise in the horses only when they received the control
      treatment. Plasma lactate concentration was increased by exercise but was not
      affected by feeding state. Plasma free fatty acid concentrations were highest
      when the horses received the control treatment. In addition, when horses received
      the control treatment, plasma free fatty acid concentrations decreased during the
      warm-up and high intensity phases of the test and increased during the walk
      phase. Free fatty acid concentrations changed in the horses receiving 1, 2 or 3
      kg of corn grain only during the high intensity phase of the exercise test.
      Feeding status affects the metabolic response of horses to exercise thus further
      studies are necessary to evaluate the effect of feeding status on exercise
      performance.

PMID- 8263612
TI  - In vitro production of short-chain fatty acids by bacterial fermentation of
      dietary fiber compared with effects of those fibers on hepatic sterol synthesis
      in rats.
AB  - The aim of this study was to determine the effects of fiber feeding on short
      chain fatty acid (SCFA) production in laboratory rats and in an in vitro
      fermentation model using fecal inocula from rats adapted to a high fiber diet. In
      addition, the effect of fiber intake on endogenous sterol synthesis was
      evaluated. Twenty male Sprague-Dawley rats were divided into four groups and fed
      a control or 30% fiber diet (cellulose, pectin or pea fiber) for 4 wk. In vitro
      fermentation was compared with measurements of cecal SCFA content of fiber
      adapted rats. Sterol synthesis in isolated hepatocytes was determined in groups
      of five to seven rats fed 15% dietary fiber for 4 wk. Cellulose was poorly
      fermented in both the in vitro and in vivo experiments. Pectin fermentation
      produced high levels of propionate, whereas pea fiber was associated with notable
      butyrate production. Adaptation to pectin produced seven times more SCFA in rat
      cecal contents (515 +/- 78 mumol) in comparison to a fiber-free diet (70.6 +/-
      4.9 mumol), with similar results observed in vitro. Sterol synthesis in
      hepatocytes of rats fed pectin was significantly greater than in those of control
      or cellulose-fed rats. Despite significantly higher rates of SCFA production in
      pectin-fed rats, cholesterol synthesis was not inhibited, suggesting that SCFA
      are not the cholesterol-lowering factor of highly fermentable fiber sources.

PMID- 8263611
TI  - Low dose fructose ingestion during gestation and lactation affects carbohydrate
      metabolism in rat dams and their offspring.
AB  - This study examined whether drinking fructose or glucose water with a balanced
      diet affects pregnant and lactating rats and their offspring. The animals were
      divided into three groups and drank tap water, 100 g/L fructose water or 100 g/L
      glucose water. The fructose-fed dams ate significantly more food but drank less
      water than the glucose-fed group. On d 19 of pregnancy, the fructose-fed dams had
      significantly heavier livers and significantly higher plasma glucose and insulin
      concentrations than dams consuming tap water. Five days after litters were
      weaned, dams fed fructose had the heaviest body weights, significantly higher
      plasma glucose concentration compared with the group receiving tap water and
      significantly higher plasma triglyceride concentration compared with the glucose
      fed group. Weanlings of the fructose-fed dams had significantly lower plasma
      glucose concentration but a significantly higher plasma insulin concentration
      than the weanlings of the group receiving tap water. These findings suggest that
      intake of fructose during gestation can cause hyperglycemia and hyperinsulinemia
      in dams and, at weaning, greater weight gain in dams and hyperinsulinemia in
      offspring. These abnormalities in dams and weanlings could be the result of
      insulin resistance.

PMID- 8263613
TI  - Dietary arachidonate enhances tissue arachidonate levels and eicosanoid
      production in Syrian hamsters.
AB  - Eicosanoids are oxidative derivatives of arachidonic acid. When produced in
      excess many of them are proinflammatory agents. This study investigates whether
      dietary arachidonic acid enhances arachidonic acid phospholipid content of
      various tissues and whether this enrichment increases eicosanoid production. Male
      Syrian hamsters were divided into four groups and fed diets supplemented with
      ethyl esters of oleic acid, linoleic acid, arachidonic acid or eicosapentaenoic
      acid. Differences in the composition of the phospholipid fatty acids were
      monitored in liver, lung, heart, spleen, kidney, testes, macrophages and
      platelets. In all tissues analyzed, the phospholipid content of arachidonic acid
      was significantly higher in the arachidonic dietary group compared with all other
      dietary groups (average > 50% higher). In contrast, increasing dietary linoleic
      acid by 50% had little effect on altering tissue arachidonic acid levels.
      Following in vitro stimulation, macrophages and platelets from animals maintained
      on arachidonic acid produced, in general, the highest levels of eicosanoids
      compared with cells from animals fed the other diets. Significant differences
      were observed in prostaglandin E2 (macrophages) and thromboxane B2 (platelets)
      formation when compared with the oleic acid and eicosapentaenoic acid dietary
      groups. The data demonstrate that including low to moderate levels of arachidonic
      acid in the diet increases macrophage and platelet arachidonic acid levels and
      may augment eicosanoid production.

PMID- 8263614
TI  - Intestinal calcium absorption in rats is stimulated by dietary lactulose and
      other resistant sugars.
AB  - Lactulose is a disaccharide analogue of lactose that is resistant to metabolism
      in the small intestine but not in the large intestine. The effects of lactulose
      and other sugars on intestinal Ca absorption were determined from the decrease in
      the 47Ca:47 Sc ratio between diet and feces after feeding male rats diets
      containing these sugars during a single night. Dietary lactulose was more potent
      than lactose in stimulating Ca absorption and was effective between 5 and 38 wk
      of age. The component sugars of lactulose, galactose and fructose, did not
      influence Ca absorption when provided together at concentrations equimolar to
      that of lactulose. The stimulation of Ca absorption by dietary lactulose
      increased as dietary Ca concentration was raised and was not influenced by prior
      injections of calcitriol. Lactulose must be present in the same meal as Ca to
      stimulate Ca absorption, but this stimulation was lost if the rats were fed
      lactulose continuously for 2 or 7 d prior to the test diet. Other sugars thought
      to be poorly absorbed in the small intestine (xylitol, lactobionate, arabinose,
      raffinose, pyroglutamate, sorbitol, gluconate and raftilose) stimulated Ca
      absorption to an identical extent as lactulose. Cecectomy did not influence the
      enhancement of Ca absorption by lactulose. These results indicate that sugars
      resistant to metabolism and absorption in the small intestine but not the large
      intestine stimulate Ca absorption in the small intestine.

PMID- 8263616
TI  - On the meaning of a life: what parents taught me.

PMID- 8263617
TI  - Pulmonary mechanics generated by positive end-expiratory and continuous negative
      pressure.
AB  - Pulmonary function measurements were studied on equivalent levels of positive end
      expiratory pressure (PEEP) and continuous negative pressure (CNP) while
      controlling for transpulmonary pressure (TPP). Four adult rabbits were
      anesthetized, instrumented, and ventilated with intermittent mandatory
      ventilation by using peak inspiratory pressure (PIP) of 16 cm H2O, PEEP 0 cm H2O,
      CNP 0 cm H2O, inspiratory time 0.3 seconds, rate 20/min, and fraction of inspired
      oxygen of 0.3. Subsequently, equal amounts of PEEP and CNP were alternated for 15
      minute ventilation periods. PIP was changed to approximate the TPP in each
      PEEP/CNP pair. There was a significant decrease in PCO2 and increase in pH,
      mechanical tidal volume, minute ventilation, functional residual capacity, and
      total dynamic compliance on CNP. These differences could not be explained by
      changes in TPP.

PMID- 8263615
TI  - Quantitative efficacy of niacin sources for chicks: nicotinic acid, nicotinamide,
      NAD and tryptophan.
AB  - A niacin-deficient diet based upon corn and casein was used to establish growth
      promoting efficacy of various sources of niacin activity. In the presence of
      excess dietary nicotinamide, chicks fed the corn-casein diet achieved maximal
      weight gain when 100 mg/kg of L-tryptophan was supplemented. The basal diet for
      efficacy studies therefore contained 100 mg/kg of added tryptophan and no
      supplemental nicotinic acid. Weight gain in the linear response surface of the
      growth curve proved to be a far better measure of niacin bioactivity than tissue
      accumulation of NAD(P). Slope-ratio growth efficacy studies indicated that excess
      dietary tryptophan was 1.94 +/- 0.14% as efficient as nicotinic acid in
      furnishing bioavailable niacin activity (52:1, wt:wt). Relative to nicotinic acid
      used as a standard (100%), nicotinamide bioactivity was 124%. Nicotinamide in NAD
      was utilized with an efficiency of 95% relative to nicotinamide per se.

PMID- 8263618
TI  - Neonatal morbidity between 34 and 37 weeks' gestation.
AB  - The objective of this study was to determine the risk of significant neonatal
      morbidity in women with preterm labor who deliver between 34 and 37 weeks'
      gestation. A total of 101 women between 34 and 37 weeks' gestation with
      documented preterm labor met inclusion and exclusion criteria; 90 gave informed
      consent and were randomly assigned to receive either intravenous magnesium
      tocolysis (treatment group) or conservative management with hydration, sedation,
      and observation (control group). Of the 90 women entering the study (45 in the
      treatment group and 45 in the control group), 2 discontinued tocolytic therapy
      because of gastrointestinal side effects. The gestational age on admission,
      cervical dilatation at diagnosis of preterm labor, interval to delivery, and
      birth weight were not significantly different between the treatment and control
      groups. There were no serious neonatal complications. In each group, three women
      had transient tachypnea and one had respiratory distress syndrome. We conclude
      that neonatal morbidity after delivery between 34 and 37 weeks' gestation is
      unchanged whether or not attempts to arrest labor are unsuccessful. The extra
      expense and maternal risk of tocolysis are not justified by beneficial results in
      the infant.

PMID- 8263619
TI  - Amniotic fluid surfactant-albumin ratio as a screening test for fetal lung
      maturity. Two years of clinical experience.
AB  - An automated amniotic fluid surfactant-albumin ratio (SAR) test was performed as
      a screening test for pregnancies requiring fetal pulmonary maturity testing. Of
      the 178 neonates delivered within 3 days of the testing, respiratory distress
      syndrome (RDS) developed in 21 (11.8%) and transient tachypnea of the newborn
      infant (TTN) in 11 (6.1%). A positive test was defined as one which predicted RDS
      or TTN. Sensitivity was interpreted as the proportion of neonates with RDS or TTN
      detected by SAR less than 70 mg/gm. Sensitivity was 90.7% with a specificity of
      76.1%. The positive predictive value was 45.3%; the negative predictive value
      97.4%. The interassay coefficient of variability was 3.5%. The SAR test has
      proven to be a rapid, precise laboratory tool. Our combined testing protocol uses
      the SAR as an initial screening test with the lecithin/sphingomyelin ratio used
      as backup if the SAR did not predict maturity (SAR < 70 mg/gm). This protocol has
      markedly lowered the use of lecithin/sphingomyelin ratios while maintaining
      necessary clinical accuracy.

PMID- 8263620
TI  - Use of incremental weight charts with follow-up of high-risk infants.
AB  - A retrospective descriptive study was done to determine the potential usefulness
      of using incremental weight charts in the management of infants followed in a
      high-risk infant follow-up clinic. For this study, 135 charts were reviewed and
      42 were subjected to data collection and analysis by using commercially available
      weight velocity charts. The incremental weight charts that were produced
      demonstrated that most of the infants studied had growth velocities well within
      the normal range; however, infants who had a history of bronchopulmonary
      dysplasia had a tendency to have weight velocities below the 5th percentile. Also
      observed was a correlation for infants born with a very low birth weight (< 1000
      gm) to have somewhat lower, although usually normal, percentiles for later weight
      velocity. Analysis and comparison of these incremental charts with standard
      growth charts for these infants demonstrated that incremental weight charts
      appear to be superior to standard charts in graphically demonstrating changes in
      weight over time.

PMID- 8263622
TI  - Association of patent ductus arteriosus and phototherapy in infants weighing less
      than 1000 grams.
AB  - To determine the relationship of phototherapy and patent ductus arteriosus, we
      analyzed prospectively collected data on 295 infants with birth weight of 501 to
      999 gm admitted from 1984 through 1988. Seventy-four percent were evaluated by an
      imaging study to aid in the detection of a silent patent ductus arteriosus.
      Overall incidence of patent ductus arteriosus in the study population was 63%.
      Infants who received phototherapy (n = 128) had an increased incidence of patent
      ductus arteriosus compared with those who did not receive phototherapy (76% vs
      53%). There was an association of patent ductus arteriosus and phototherapy (p <
      0.05) when we analyzed the data with a stepwise regression model that controlled
      for the effects of gestational age, birth weight, gender, race, diagnosis of
      hyaline membrane disease, mechanical ventilation, patent ductus arteriosus
      imaging studies, prophylactic indomethacin, peak total and indirect bilirubin
      values, and the occurrence of abnormal serum sodium values. We conclude that the
      use of phototherapy is associated with an increased incidence of patent ductus
      arteriosus in extremely low birth weight infants.

PMID- 8263621
TI  - Mortality prediction and interval until death in near-term and term neonates with
      respiratory failure.
AB  - Mortality risk indicators may be useful adjuncts to clinical judgment in
      considering the use of extraordinary and relatively high-risk treatments such as
      high-frequency ventilation, extracorporeal membrane oxygenation, and nitric oxide
      therapy. We retrospectively evaluated the reliability of published indications of
      high mortality, developed additional high-risk indicators, and determined the
      interval between the time when high-risk indicators were met and when death
      occurred in near-term and term neonates with respiratory failure. Patients were
      included in the analysis if they met the following criteria: > or = 35 weeks
      gestation, > or = 2 kg birth weight, < or = 7 days of age, and receiving a
      fraction of inspired oxygen of > or = 0.8 and mechanical ventilation. Patients
      were excluded if they had congenital heart disease, intracranial hemorrhage,
      untreatable bleeding diathesis, or lethal congenital anomaly. Fifteen patients in
      the 1980 to 1981 group and 41 patients in the 1985 to 1987 group met these
      criteria. We observed 100% mortality in our 1980 to 1981 patients who met
      previously published criteria predictive for > or = 80% mortality in near-term
      and term neonates with respiratory failure; however, mortality risk was 60% to
      80% in the 1985 to 1987 group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263623
TI  - Mediastinal cystic hygroma: prenatal decompression with neonatal resection and
      recurrence at 19 months of age.
AB  - A case of an anterior mediastinal cystic hygroma detected prenatally at 22 weeks'
      gestation is reported. Because of progressive nonimmune hydrops, cardiac
      compromise, and mediastinal shift compressing the lungs, in utero decompression
      was successfully performed at 24 weeks. This newborn infant was delivered at 37
      weeks' gestation with no respiratory distress. Operative excision of a large
      thoracic cystic hygroma was performed shortly after birth. At 19 months of age,
      this patient appeared with unilateral wheezing and fever. Operative findings
      confirmed recurrence of a cystic hygroma.

PMID- 8263624
TI  - Is fetal growth affected by cord entanglement?
AB  - Cord entanglement is a common occurrence during delivery. We examined the
      association of cord complications observed at delivery and birth weight. A
      retrospective survey of 12,241 births was performed, supplemented with a
      prospective study of an additional 456 deliveries. No adverse association was
      found in the retrospective data between cord coiled twice or more around the
      newborns' neck (8.3% of cases) and birth weight. Moreover, the incidence of cord
      around neck was significantly lower (p < 0.0006) in infants weighing less than
      2000 gm at birth. A multiple regression analysis of the prospective data did not
      reveal any significant influence of cord complications on birth weight. We
      conclude that cord entanglement was not found to be a major cause of intrauterine
      disadvantage in pregnancies with a viable infant at term, as reflected by birth
      weight.

PMID- 8263625
TI  - Managed competition and perinatal care: what does the future hold?

PMID- 8263626
TI  - Born too soon.

PMID- 8263627
TI  - Tricuspid valve vegetation caused by group B streptococcal endocarditis:
      treatment by "vegetectomy".

PMID- 8263628
TI  - Treatment of Candida arthritis with flucytosine and amphotericin B.
AB  - A premature infant with disseminated Candida tropicalis infection with arthritis
      and osteomyelitis is presented. Although the organism was susceptible to
      amphotericin B, synovial fluid cultures were still positive for yeast after 2
      weeks of intravenous amphotericin B therapy. The addition of oral flucytosine (25
      mg/kg four times daily) resulted in sterilization of the synovial fluid within 4
      days. Simultaneous serum and synovial levels of flucytosine were 47.5
      micrograms/ml and 39.6 micrograms/ml, respectively. This is the first
      documentation in the medical literature of intraarticular levels of flucytosine,
      and provides further rationale for the use of flucytosine in addition to
      amphotericin B in patients with Candida arthritis.

PMID- 8263629
TI  - Fetal heart rate monitoring casebook. Sinusoidal FHR pattern.

PMID- 8263630
TI  - Special imaging casebook. Congenital cystic adenomatoid malformation, type I.

PMID- 8263631
TI  - Neonatal radiology casebook. Pneumoretroperitoneum.

PMID- 8263632
TI  - Preeclampsia.

PMID- 8263633
TI  - Infant with respiratory disease and persistent hypoxemia.

PMID- 8263634
TI  - Divided we stand.

PMID- 8263635
TI  - Functional consequences of partial glossectomy.
AB  - The postsurgical deglutition, oral suction, and speech capabilities of 11
      patients who had undergone partial glossectomy for squamous cell carcinoma of the
      lateral aspect of the tongue were compared with that of 20 healthy control
      subjects. Volume swallowed per second and speech quality were significantly
      correlated with the area of tongue removed. Three patients subjected to a second
      operation to improve the mobility of the residual tongue regained almost normal
      speech intelligibility. In general, functional performance was better than
      expected, which justifies a radical surgical approach to this kind of tumor.

PMID- 8263636
TI  - Prosthodontic complications related to compromised implant placement.
AB  - Successful prosthodontic treatment is dependent on optimal placement of the
      endosseous implants. This article describes prosthodontic problems associated
      with nonoptimal implant placement and suggests clinical guidelines to minimize
      recurrence of these problems.

PMID- 8263637
TI  - Temporomandibular joint reconstruction of the complex patient with the Techmedica
      custom-made total joint prosthesis.
AB  - A study of 56 patients (55 female, one male) with 100 reconstructed
      temporomandibular joints (TMJ) using the Techmedica custom-made total joint
      system (Techmedica Inc, Camarillo, CA) is presented. The patients ranged in age
      from 15 to 61 years (average, 39 years) and had 16 to 46 months' follow-up
      (average 30 months). Outcome groups were categorized as good, fair, or poor,
      based on clinical assessment. Results show that 35 patients (63%) with 58 joints
      (58%) had a good outcome, and 13 patients (23%) with 26 joints (26%) had a fair
      outcome, and 8 patients (14%) with 16 joints (16%) had a poor outcome. Patients
      with one or no previous temporomandibular joint surgeries had 86% in the good
      group, 14% in the fair group, and no patients in the poor group. In patients with
      two or more previous surgeries, the success rate decreased to 55% with good
      results, 26% with fair results and 19% with poor results. Long-term morbidity
      included five ramus prostheses that were removed or revised. Seventeen patients
      (30%) received further operations because of heterotopic bone formation,
      fibrosis, calcification, inflammation, and/or pain which occurred mostly in
      patients with previous Proplast/Teflon (Vitek, Inc, Houston, TX) implants.
      Continued pain has been associated with the poor group, which may be related to
      problems such as cervical neuropathy, sympathetic dystrophy, a residual
      inflammatory or immunologic reaction to Proplast/Teflon or silastic particles,
      fibrosis, calcification, heterotopic bone, or other unidentified factors.

PMID- 8263638
TI  - Mandibular involvement in patients with multiple myeloma.
AB  - A survey of changes in the jaw bones of 38 patients with multiple myeloma
      revealed five cases with mandibular involvement. One case showed a pathological
      fracture of the mandibular angle, and in another case, a radiolucent area was
      found in the body of the mandible. These two clinical findings led to the
      diagnosis of multiple myeloma. The other three cases had no symptoms related to
      the oral region. All five cases also showed typical "punched-out" lesions in the
      skull. It is suggested that a skeletal radiologic survey including the jaw should
      be performed in patients with multiple myeloma.

PMID- 8263639
TI  - Isolation of Actinomyces species and Eikenella corrodens from patients with
      chronic diffuse sclerosing osteomyelitis.
AB  - Cultures from 26 patients with chronic diffuse sclerosing osteomyelitis of the
      mandible were studied. In most cases there was a mutualistic infection involving
      any one of the known human Actinomyces species together with Eikenella corrodens.
      In a few cases, Arachnia species were substituted for Actinomyces and gram
      negative anaerobes for E corrodens. The specific culture protocol used to
      identify these organisms from clinical specimens is described. Taxonomic and
      experimental evidence that supports an infectious etiology are presented.

PMID- 8263640
TI  - Evaluation of dexamethasone for reducing postoperative edema and inflammatory
      response after orthognathic surgery.
AB  - A randomized, prospective, double-blind study was conducted to determine the
      efficacy of intravenous dexamethasone in reducing postoperative edema after
      bilateral sagittal split osteotomies of the mandible. Twenty-three patients were
      enrolled in the study and randomly assigned to one of the three groups. Each
      patient received one preoperative infusion and three postoperative infusions
      every 6 hours. Seven patients served as controls and received placebos for all
      infusions. Eight patients received dexamethasone, 16 mg preoperatively and three
      placebo postoperative doses. Eight patients received dexamethasone, 16 mg
      preoperatively and three 8-mg postoperative doses. Facial edema was quantified by
      computer scanning of standardized photographs. The underlying inflammatory
      process also was measured using C-reactive protein, erythrocyte sedimentation
      rate, and complete blood counts. Five sets of photographic and laboratory data
      were obtained for each patient: preoperative, day of surgery, and postoperative
      days 1, 2, and 3. Patients receiving dexamethasone demonstrated significantly
      less postoperative edema only on postoperative day 1 (P < .05) when measured
      photographically. C-reactive protein was significantly reduced on postoperative
      days 1, 2, and 3 (P < .05) in both dexamethasone groups. No significant
      difference was found between the two dexamethasone groups. Measurement of C
      reactive protein seems to be the most sensitive method for comparing the effect
      of dexamethasone on postoperative inflammation. Preoperative intravenous
      dexamethasone significantly reduced postoperative inflammation and its associated
      edema after orthognathic surgery.

PMID- 8263641
TI  - Pharyngeal airway changes associated with mandibular advancement.
AB  - This study analyzes changes in the anteroposterior dimension of the oropharynx as
      determined from lateral cephalometric radiographs on 26 patients who have
      undergone mandibular advancement. Increases in the sagittal dimensions of the
      oropharynx were unpredictable and tended to decrease with time, suggesting that
      mandibular advancement may be an unreliable method of treating obstructive sleep
      apnea. The most stable long-term results were found in those cases with narrowing
      of the oropharynx preoperatively.

PMID- 8263642
TI  - The effect of screw size and insertion technique on the stability of the
      mandibular sagittal split osteotomy.
AB  - The effect of screw size and insertion technique on the stability of sagittal
      split osteotomies was evaluated on 10 cadaver mandibles. The mandibles were
      osteotomized, and stabilized with either 2.0- or 2.7-mm stainless steel screws
      inserted as lag screws or position screws. All specimens were tested on an MTS
      servohydraulic testing machine (MTS Systems, Inc, Minneapolis, MN) to determine
      the strength and stability of the fixation. There were no statistically
      significant differences between the strengths achieved with the different screw
      sizes or fixation techniques. The primary variable that determined stability
      seemed to be the quality of the underlying bone.

PMID- 8263643
TI  - Polylactide inhibition of carcinoma cell growth in vitro.
AB  - Normal fibroblasts and epithelial tumor cells were challenged by exposure for 24
      hours to extracts of a pure metal, a metal alloy, and a polymer used in facial
      reconstruction to assess cellular growth effects. While none of these materials
      significantly altered fibroblast growth rates, poly-L-lactide inhibited carcinoma
      cell growth at 5.0% extract concentration. No carcinoma cell growth effects were
      seen from exposure to stainless steel or commercially pure titanium extracts.

PMID- 8263645
TI  - Enhancement of bone ingrowth into a porous hydroxylapatite-matrix using a
      resorbable polylactic membrane: an experimental pilot study.
AB  - The objective of this pilot study was to study bone ingrowth into porous
      hydroxylapatite (HA) blocks using a polylactic membrane for guided tissue
      regeneration. Porous HA blocks were placed on both sides of the mandible and of
      the ilium in five Gottingen minipigs. On one side a polylactic membrane was used
      to cover the blocks. After 5 months, the blocks with the membrane covering showed
      complete bony penetration of the HA matrix both in the mandible and the ilium.
      The blocks without the membrane covering showed substantially less and irregular
      bone ingrowth after placement on the mandible and poor ingrowth after placement
      on the ilium. The newly formed bone in the blocks from the ilium showed a
      cancellous structure while bone tissue inside the blocks from the mandible
      exhibited a dense cortical appearance. The polylactic membrane was nearly
      completely degraded at the time of investigation.

PMID- 8263644
TI  - Interfacial reactions of osteoblasts to dental and implant materials.
AB  - Scanning electron microscopy was used to study the response of osteoblasts to
      various surfaces including ceramics and glasses as well as steel and titanium.
      Hydroxylapatite, tricalcium phosphate, bioglass, steel, and titanium supported
      cell adhesion. However, the toxic effects of the In-Ceram (Vita, Bad Sackingen,
      Germany), and feldspar ceramic and glaze were severe enough to cause verrucous
      necrosis that was identifiable after 2 days of culture. After 10 days in culture
      only the peripheral portions of these specimens were still occupied by cells; the
      cells in the central portion of the circular specimens had succumbed to necrosis.
      It was concluded that scanning electron microscopy is useful in identifying the
      response of cells to materials. Pathologic changes are not recognizable if they
      are limited to the internal structure of the cell, but readily discernible when
      they impinge on the morphologic integrity of the cell surface.

PMID- 8263646
TI  - Sagittal magnetic resonance image characteristics and surgical findings of
      mandibular condyle surface disease in staged internal derangements.

PMID- 8263647
TI  - Painless neck mass and nasal congestion.

PMID- 8263648
TI  - Lemierre's syndrome: two cases of a forgotten disease.

PMID- 8263649
TI  - Combined transconjunctival lateral canthotomy approach for infraorbital nerve
      exploration: report of a case.

PMID- 8263650
TI  - Delayed diagnosis of the cause of facial pain in patients with neoplastic
      disease: a report of eight cases.

PMID- 8263651
TI  - Recurrent osteoblastoma of the mandible: a case report.

PMID- 8263652
TI  - Arthroscopic diagnosis and treatment of temporomandibular joint synovial
      chondromatosis: report of a case.

PMID- 8263653
TI  - Keeping discussions on an even plane.

PMID- 8263654
TI  - Dynamic response of the adult monkey maxilla to occlusal forces.
AB  - We investigated the magnitude of various maxillary occlusal forces and the
      direction in which such forces were propagated. Adult monkeys were anesthetized
      and forced to occlude on sticks of 3, 5 and 7 mm thickness at the canines, second
      premolars and second molars. Electrical stimulation was applied to the masseter
      and temporalis muscles, and measurements of magnitude, direction and character of
      principal strains were recorded. Readings for the surface of the maxilla
      indicated that bone sutures and adjacent cavities are intimately and functionally
      related to the buffering of these occlusal forces. The maxilla deformed as the
      premaxilla was pushed out in the region of the premaxillomaxillary suture. The
      nasal bone was stretched anteroposteriority in the region of the nasomaxillary
      suture as the space that arose due to contraction of the masseter muscle was
      filled in the region of the zygomaticomaxillary suture. In addition, when
      occlusal forces were imparted on the maxilla, the surfaces of this bone bulged
      out due to the effect on adjacent bone cavities. Results demonstrated that the
      maxilla dispersed occlusal force well by these mechanisms. Accordingly, there
      were very few regions in this bone where stresses concentrated.

PMID- 8263655
TI  - Age-related changes in central nervous system hyaluronic acid and chondroitin
      sulfate in senescence-accelerated mice.
AB  - Age-related changes in cerebral hyaluronic acid (HA) and chondroitin sulfate (CS)
      in senescence-accelerated mice (SAM-P/8 parallel Odu, P substrain) were
      investigated. SAM-R/1 parallel Odu (R substrain) mice were used as controls.
      Levels of both HA and CS extracted from the defatted dry cerebrums at 7, 17, 27
      and 37 weeks of age were determined by HPLC analysis after conversion to
      unsaturated disaccharides following enzymatic digestion. Glycosaminoglycan
      content (determined as uronic acid) was lower in P substrain mice than in the age
      matched controls at all ages tested. Though the ratio of HA to CS was increased
      at 17 and 27 weeks in control mice, this ratio for the P substrain was already
      high at the initial test at 7 weeks and remained so thereafter. The CS chain
      consisted mainly of delta Di-4S, with delta Di-0S and delta Di-6S present only as
      minor components at all ages in both substrains. The HA chain consisted only of
      delta Di-HA for all ages in both substrains. The relative amount of each
      unsaturated disaccharide was higher in the R substrain than in the P substrain
      mice at all ages. We found that qualitative and quantitative changes in cerebral
      CS and HA were expressed relatively early in the P substrain mice compared to
      controls. We propose that these changes are associated with and may cause
      physiological and functional alterations associated with senescence in the CNS.

PMID- 8263656
TI  - Effect on the dentofacial complex of Macaca irus of functional tongue forces
      imparted on a palatal bar.
AB  - I determined the effect tongue forces imparted on a palatal bar has on the growth
      and development of the dentofacial complex of the Macaca irus. Ten female Macaca
      irus monkeys with mixed dentition were used in this experiment. The animals were
      divided into four groups, two animals were treated for 30 days, two for 90 days,
      and four for 180 days, with the remaining two animals serving as controls. The
      following results were obtained. 1. There was disocclusion on the maxillary and
      mandibular first molars. 2. Elongation of the mandibular first molars resulted
      from intrusion of the maxillary first molars. 3. The maxillary complex displayed
      a positional change with slight clockwise rotation. 4. Growth of the
      frontozygomatic site in the anteroinferior direction was inhibited. 5. There was
      no anterosuperior mandibular growth. 6. Changes in the maxillary suture and
      positioning of the teeth were mainly due to the effects of the tongue function
      imparted on the palatal bar. With enough control of the vertical growth of the
      maxilla can be validated. This is one of many methods of treating Class II
      malocclusion.

PMID- 8263657
TI  - Health care and the pharmaceutical industry.

PMID- 8263658
TI  - Sorption of bacterial endotoxin and retention of bacteria by positively charged
      membrane filters.
AB  - Positively charged membrane filters (Pall, Posidyne) were studied for their
      ability to retain both bacterial endotoxins and bacteria. Filters (0.2 microns
      pore size) were challenged with high (up to 5* 10(5) EU) levels of bacterial
      endotoxin. When the endotoxin was dispersed in water, a more than 10,000 fold
      reduction of the endotoxin was obtained, whereas the reduction was only a factor
      20 when Ringer's solution was used to disperse the endotoxin. Retention of
      bacteria was dependent on the type of organism, the pore size of the filter and
      the suspending liquid. Although filters with pore sizes > 0.2 microns were not
      suitable to be used as a final filter in an aseptic production process, a very
      reduction in the number of bacteria could be obtained. Possible applications for
      these filters in the production of sterile pharmaceuticals are discussed.

PMID- 8263659
TI  - Influence of copper, iron, and zinc on the physicochemical properties of
      parenteral admixture.
AB  - A parenteral admixture composed of 25% of 20% Intralipid, 25% of Azonutril 25,
      37.5% of 30% Glucose and 12.5% of 50% Glucose was supplemented with copper, iron
      and zinc in the organic (gluconate) or inorganic (chloride) form at the following
      usual final concentrations: copper 0.24 mg/L, iron 0.50 mg/L, zinc 2.00 mg/L. The
      mixture was stored at 4 degrees C and at 25 degrees C for 24, 48, and 72 hours,
      and for one week. Determination of the pH indicated good stability of the mixture
      containing the trace elements in the gluconate form. A significant decrease in
      the pH of the mixture containing the trace elements as chlorides was noted after
      one week of storage at both temperatures. Particle size analysis revealed no
      significant variations between the two formulations after one week of storage.
      Flocculation kinetics confirmed the results obtained with the other two methods
      used to determine physicochemical stability. In addition, the kinetics indicated
      that the possibilities of coalescence processes are highly reduced in all cases.
      It may be concluded that the two type of mixtures remain stable for Seven days at
      4 degrees C and 25 degrees C. However, mixtures containing trace elements in
      gluconate form should be chosen in cases of longer storage.

PMID- 8263660
TI  - An approach to the determination of endotoxin in anesthetics and antibiotics: use
      of an ultrafiltration system and enzymatic LAL reaction.
AB  - An ultrafiltration system is used to obtain an endotoxin-free buffer for the LAL
      test. The procedure is combined with a kinetic LAL reaction of high sensitivity.
      This approach allows for the easy determination of endotoxin levels in
      parenterals with LAL-interfering substances, reducing the maximum valid dilution
      necessary for use in product development.

PMID- 8263661
TI  - Automated method for determining Instron Residual Seal Force of glass vial/rubber
      closure systems.
AB  - Instron Residual Seal Force (IRSF) of glass vial/rubber closure systems was
      determined using an Instron 4501 Materials Testing System. Computer programs were
      written to process raw data and calculate IRSF values. Preliminary experiments
      indicated both the appearance of the stress-deformation curves and precision of
      the derived IRSF values were dependent on the internal dimensions and top surface
      geometry of the cap anvil. Therefore, a series of five cap anvils varying in
      shape and dimensions were machined to optimize performance and precision. Vials
      capped with West 4416/50 PURCOAT button closures or Helvoet compound 6207
      lyophilization closures were tested with each cap anvil. Cap anvils with
      spherical top surfaces and narrow internal dimensions produced more precise
      results and more uniform stress-deformation curves than cap anvils with flat top
      surfaces and wider internal dimensions.

PMID- 8263662
TI  - The incubation period in sterility testing.
AB  - Sterility test results gathered over a ten year period have been analysed to
      determine the effects of the incubation period. Overall there was no difference
      between the membrane filtration test and direct inoculation in the time required
      for visible growth of contaminants. Growth occurred earlier if products had no
      preservative or antimicrobial substances. However use of the membrane filtration
      method did not significantly enhance the efficiency of detection at seven days
      incubation. Regardless of the nature of the product or the method of test an
      unacceptable proportion of contaminants would be missed by limiting incubation to
      seven days.

PMID- 8263663
TI  - Destruction of typical endotoxins by dry heat as determined using LAL assay and
      pyrogen assay.
AB  - The kinetics of destruction by dry heat of two typical endotoxins, Escherichia
      coli 055:B5 (E. coli endotoxin) and Salmonella abortus equi (S. abortus equi
      endotoxin), were determined using the Limulus Amebocyte Lysate (LAL) and pyrogen
      assays. The efficiency of recovery of these endotoxins from carriers using a
      pyrogen assay was also determined simultaneously. In the LAL assay 0.1-10,000 EU
      was used and 10-1000 EU in the pyrogen assay. Recoveries of E. coli endotoxin and
      S. abortus equi endotoxin were, respectively, 49.7-92.0% and 27.0-70.1% by the
      LAL assay, and 31.1% and 60.6% by the pyrogen assay. Fourier transformation
      infrared (FT-IR) spectra demonstrated the presence of chemical structural
      differences between the two endotoxins. By dry heat (200 or 250 degrees C), there
      were no significant differences in the destruction kinetics between the two
      endotoxins; either endotoxin can therefore be adapted for use in the endotoxin
      challenge test. Destruction in the pyrogen assay was significantly quicker than
      that predicted by the LAL assay for each of the two endotoxins. In this endotoxin
      destruction system, 3 log cycle reduction (the United State Pharmacopeia (USP)
      recommendation for the depyrogenation process) could not be obtained by challenge
      with 10,000 EU of endotoxin under the depyrogenation conditions of 200 degrees C
      for 60 min (a set of conditions described in the European Pharmacopoeia (EP)),
      though little pyrogenicity remained. On the other hand, at 250 degrees C for 30
      min (a set of conditions described in the EP, USP and Pharmacopoeia of Japan
      (JP)),a 3 log cycle reduction was achieved without any pyrogenicity remaining.

PMID- 8263664
TI  - Evaluation of the influence of open and closed-ampoule technologies on
      particulate matter in small-volume parenterals.
AB  - SVP in glass ampoules are manufactured using two main different technological
      production processes: the open-ampoule process (O) and the closed-ampoule process
      (C). In principle, the open-ampoule production technology should lead to better
      controlled production process. To test this hypothesis and quantify the possible
      qualitative differences in the manufactured ampoules, a suitable experimental
      design was set up. The two ampoule production processes have been compared on the
      basis of the visible particulate burden. Two batches of ampoules filled with
      water for injections were produced for each type of process, following
      conventional industrial procedures. Two samples of 20,000 units were taken from
      each batch and inspected with different automatic inspection systems: two
      Brevetti CEA machines (S1, S2--light scattering) and two EISAI machines (S3, S4-
      light absorbtion). The comparison between the processes was based on the
      rejection percentage. On both inspection machines the open-ampoule production
      samples present rejection percentages (ranging from 0.154% to 1.248% rejection
      percentages) which, on average, are lower than those detected in closed-ampoule
      production (ranging from 1.434% to 3.86% rejection percentages). The difference
      between the two processes is even more marked if we also consider the data
      obtained using inspection machines S3 and S4. The substantial differences in
      performance of the four inspection machines stress the need to provide for
      adequate validation procedures.

PMID- 8263665
TI  - Particulate contamination from siliconized rubber stoppers--a statistical
      evaluation.
AB  - Siliconized stoppers, when used with parenteral drug products, have been shown to
      be a source of particulate contamination. In this study, five different
      variables: pH of the solution, buffer concentration, Teflon coating on the
      stopper, autoclaving cycle (F0), and lot-to-lot variation of the siliconization
      process were evaluated using an eight-run Plackett-Burman design with respect to
      their impact on the level of particulate contamination from siliconized stoppers.
      Results show that pH of the solution can significantly affect the particulate
      level of samples using siliconized stoppers (p < 0.05). An alkaline solution (pH
      = 8) was shown to produce a higher particulate load than an acid solution (pH =
      4). The main effect of the remaining four variables was determined to be
      statistically insignificant (p > 0.15).

PMID- 8263666
TI  - A model for the inclusion of a physical fitness and health promotion component in
      a chemical abuse treatment program.
AB  - Alcohol and other substance abuse treatment programs are focusing more on the
      wellbeing of the total patient rather than just targeting functional sobriety.
      Various explanations are offered in this article for the inclusion of a fitness
      and health promotion component in a chemical abuse treatment program. The
      treatment program at Charter Hospital of Fort Worth, Texas, is discussed in
      detail, including a comprehensive medical examination, fitness and nutritional
      screenings, and appropriate exercise activities. Educational sessions are offered
      on health fitness, risk reduction, stress management, smoking cessation, proper
      nutrition and the positive psychological aspects of exercise. The implications of
      a health/fitness component in the recovery process are emphasized.

PMID- 8263667
TI  - Substance use and abuse among deviant and non-deviant adolescents in Israel.
AB  - The study examined the hypothesis that the use of psychoactive substances is
      strongly associated with social deviance. Patterns of alcohol and drug use among
      two samples of deviant adolescents were investigated and compared to patterns of
      use among a sample of non-deviant youths. The participants were as follows:
      ninety-seven juvenile delinquents, inmates in institutions, aged twelve through
      eighteen; 184 detached youth, aged twelve through eighteen, who are in treatment
      programs of the Departments of Youth Advancement, Ministry of Education &
      Ministry of Welfare; and a nationwide representative sample of 8151 high school
      students, aged twelve through eighteen. Substance use was measured by three self
      report indices: frequency of use during the last year, use during the last month,
      and use during the last week. The results clearly indicate that psychoactive
      substance use is concentrated among Israeli groups of deviant adolescents. These
      adolescents use all types of substances, licit as well as illicit, at rates
      considerably exceeding those found among high school students. However, a great
      similarity was found between the deviant groups of adolescents and the high
      school students in several personality correlates (sensation seeking, anxiety,
      depressive mood and learned resourcefulness) of substance use, and to a much
      lesser degree in its interpersonal correlates (perceived closeness to parents and
      to peers). The results' implications for prevention are discussed.

PMID- 8263668
TI  - College students' views of excessive drinking and the university's role.
AB  - Views of college students (N = 133) regarding excessive drinking were explored in
      terms of the amount of drinking which constitutes a drinking problem, the
      behaviors that indicate a student has been drinking excessively, and university
      alcohol policies that students would endorse. Students accepted levels of
      drinking by peers that markedly exceed definitions of excessive drinking by
      experts. A sizable minority of students refuse to label very dangerous behaviors
      associated with excessive drinking as indicating a drinking problem. The views of
      male and female students differed only marginally. Since students seem to define
      excessive drinking in ways that differ from professionals, it is suggested that
      student affairs personnel need to plan programs that recognize the students'
      views, otherwise students may continue to believe that while excessive drinking
      is bad, their level of drinking cannot lead to any problems.

PMID- 8263669
TI  - Drug use in a small midwestern community and relationships to selected
      characteristics.
AB  - A description of 1074 high school students' alcohol and other drug (AOD) use
      along with the consequences of such use was supplemented with comparisons of
      grade level and gender differences and analyses of the relationships between AOD
      use and incidence of adverse consequences with grade point average, attendance at
      religious services, frequency of dating, frequency of driving a car and frequency
      of having trouble at school. Alcohol was clearly the drug of choice and produced
      a variety of adverse consequences. Most frequently reported were arguments,
      trouble with parents and at school and nausea or vomiting. Grade level
      differences were found, but few significant gender differences emerged.
      Significant relationships between AOD use and consequences with all other
      independent variables were found.

PMID- 8263670
TI  - Drug-related HIV risk behaviors and cocaine preference among injection drug users
      in Los Angeles.
AB  - Based on a 1988-91 sample of 422 drug-using arrestees in Los Angeles, this study
      compares the drug-related risk behavior of users whose preferred injection drug
      is cocaine and users with a preference for heroin or no preference between the
      two drugs. Cocaine preference is unrelated to the likelihood of needle sharing
      overall, needle sharing with strangers, needle sharing at shooting galleries, and
      failure to use bleach as a needle disinfectant. In analyses restricted to users
      who reported needle sharing, the frequency of sharing is no more closely related
      to heroin injection frequency than to cocaine injection frequency. These results
      suggest that local preventive education programs do not need to address
      distinctive patterns of drug-related risk behavior among injection cocaine users
      and injection heroin users in Los Angeles.

PMID- 8263671
TI  - Structural equation model tests of patterns of family interaction, peer alcohol
      use, and intrapersonal predictors of adolescent alcohol use and misuse.
AB  - A survey of 1,340 students in grades six through twelve was conducted to test, in
      the context of structural equation models, the predictive validity of a
      theoretical model of antecedents of adolescent alcohol use and misuse. Constructs
      including parents' alcohol use, older siblings alcohol use, parents' approval of
      students alcohol use, older sibling approval of students alcohol use, peer use
      and approval of alcohol use (PUA), parental nurturance, parental permissiveness,
      child's grade in school, susceptibility to peer pressure (SPP), and deviant self
      image, were included. The final iterations of the models accounted for more than
      half of the variance in both alcohol use and alcohol misuse. In a standardized
      solution, the two largest direct effects on both adolescent alcohol use and
      misuse were from SPP and PUA. When a seven item measure of SPP, including three
      items specific to alcohol use was used, the SPP latent variable accounted for a
      somewhat greater percentage of the variance in adolescent alcohol use and misuse
      than did the latent variable of PUA. When the three alcohol-specific items were
      deleted from SPP, however, PUA accounted for more variance than SPP. Other
      predictors, including parental behaviors, proved to be significant when their
      indirect effects were evaluated. Models predicting alcohol use and alcohol misuse
      were similar. SPP, PUA, and other significant predictors should be included in
      future models predicting adolescent alcohol use and misuse, as well as in future
      interventions targeting these behaviors. Longitudinal studies should be used to
      test these findings. Evaluation of prevention should include examination of
      possible interactions of these predictors with each other and with subject
      subgroup classifications.

PMID- 8263672
TI  - Microcapsules for food.
AB  - A systematic description of various processes employed for microencapsulation of
      food additives is presented. Microencapsulation methods covered include spray
      drying, fluidized bed coating, extrusion, solvent extraction, coacervation,
      cocrystallization, liposome formation and molecular inclusion. Basic features of
      microcapsular products, such as morphology, particle size, core/coat
      characteristics, and release behaviour, are also highlighted.

PMID- 8263673
TI  - Effect of polybutadiene on the encapsulation efficiency of ethyl cellulose
      microcapsules of sulphadiazine.
AB  - The coacervation-inducing effect of polybutadiene (PBD), a liquid telomer of
      butadiene, in microencapsulation of sulphadiazine was investigated, using phase
      separation coacervation of ethyl cellulose, by solvent alteration, in heavy
      mineral oil medium. The effects of protective colloids and core-wall ratio on
      encapsulation efficiency were studied. Efficacy of PBD was studied compared to
      polyisobutylene (PIB). Experimental results revealed that PBD ensured better
      encapsulation efficiency compared to PIB.

PMID- 8263674
TI  - Biodegradable microspheres of poly(DL-lactic acid) containing piroxicam as a
      model drug for controlled release via the parenteral route.
AB  - Poly(DL-lactic acid), synthesized in this laboratory from DL-lactic acid, was
      used to prepare microspheres containing piroxicam, using a solvent evaporation
      technique. The microspheres obtained were characterized for their surface
      characteristics (by SEM), surface charge, density, particle size distribution,
      glass transition temperature, drug incorporation and encapsulation efficiency, IR
      spectroscopy and in vitro drug release. The suspension of microspheres was
      evaluated for its syringeability. The effect of channelling agents such as PVP
      and PEG 6000 on in vitro drug release was studied. The effect of gamma-radiation
      on poly(DL-lactic acid) and on the in vitro release of piroxicam from the
      microspheres was also studied.

PMID- 8263675
TI  - Preparation of microcapsules masking the bitter taste of enoxacin by using one
      continuous process technique of agglomeration and microencapsulation.
AB  - In order to mask the bitter taste of drugs, a novel microencapsulation process
      combined with the wet spherical agglomeration (WSA) technique was developed by
      using a modified phase separation method. The spherical agglomerates of enoxacin
      (ENX) with various additives including disintegrants were successfully produced
      in the system of acetone-n-hexane-ammonia water or acetone-n-hexane-distilled
      water by the WSA, using flocculation phenomena of particles in liquid. Resultant
      agglomerates could be microencapsulated continuously with Eudragit RS utilizing
      the phase separation method in the same system as agglomeration under stirring.
      'Explosible' microcapsules which were free from the bitter taste could be
      produced in formulating finer particle size of ENX and 50 per cent of Primojel in
      core agglomerates, using distilled water as a bridging liquid, and treating with
      20 per cent polymer coating level. These microcapsules were bioequivalent to the
      commercial ENX 100 mg tablets in beagle dogs. One continuous process technique of
      agglomeration and microencapsulation was useful for the design of ENX powders
      which masked the bitter taste and controlled the drug release rate.

PMID- 8263676
TI  - Preparation and performance of chitosan encapsulated activated charcoal (ACCB)
      adsorbents for small molecules.
AB  - A technique is described to encapsulate activated charcoal for haemoperfusion to
      be used in an artificial liver support. Activated charcoal was encapsulated
      within chitosan matrix (ACCB) in different concentrations, and was used as the
      supports for perfusion of a mixture of solutes, having molecular weight ranges
      from 60 to 69,000; under a flow rate of 8 ml/min. It seems the ACCB may be a good
      adsorbent system for the removal of toxic uric acid, creatinine, bilirubin, etc.,
      from solutions; while larger molecules such as albumin are adsorbed less. The
      encapsulated charcoal did not leach out from the matrix during perfusion, and the
      system may be useful for detoxification of blood. The haemolytic potential of
      ACCB has been compatible with polystyrene control tubes. However, further studies
      are needed to determine their behaviour under clinical conditions.

PMID- 8263677
TI  - Evaluation of spray drying as a method for polylactide and polylactide-co
      glycolide microsphere preparation.
AB  - Polylactide and polylactide-co-glycolide microspheres containing a lipophilic
      model drug (vitamin D3) were prepared by spray drying. The purpose of this work
      is to evaluate the efficacy of spray drying as a method for microsphere
      preparation. The study was carried out on five different polymers of lactide
      class: poly-L-lactide 57000 MW, poly-D,L-lactide 209,000 MW, 109,000 MW, 16,000
      MW, and polylactide-co-glycolide 22,000 MW. The process conditions were
      experimentally assessed for each polymer used. The microspheres obtained were
      characterized for their shape, size and drug content, and the influence of the
      polymer on microsphere characteristics was evaluated. Results show that polymer
      type, polymer molecular weight and its concentration in the spraying solution
      greatly affect microsphere characteristics. In vitro dissolution tests performed
      with the rotating bottle method resulted in different release profiles depending
      on type of polymer and on microsphere morphology.

PMID- 8263678
TI  - Retinoic acid enhances killing of neuroblastoma cells by Newcastle disease virus.
AB  - Newcastle disease virus (NDV), an avian pathogen, selectively replicates in and
      kills neuroblastoma (NB) cells, but not normal fibroblasts in vitro and in vivo
      in nude mice. NDV cytotoxicity towards NB cells is enhanced by N-myc oncogene
      amplification. To further define the antineoplastic effects of NDV, we examined
      NDV's interaction with NB cells following short-term exposure to the
      differentiating agent, all-trans retinoic acid (RA), and to neuraminidase. The
      human NB cell line IMR-32, after treatment with 50 mumol/L RA, became eight times
      more sensitive to NDV in a cytotoxicity assay. A time course study to determine
      the optimal incubation period of IMR-32 cells with RA indicated that a fourfold
      increase in sensitivity towards NDV killing occurred after only 8 hours of RA
      incubation prior to addition of virus. Maximal sensitivity was achieved at 24
      hours of RA incubation and remained constant for longer incubation periods (up to
      72 hours). The sensitization of IMR-32 NB cells to NDV was constant for RA doses
      between 3 mumol/L and 50 mumol/L. Plaque formation, which indicates replication,
      virus spread and cytotoxicity by a single infectious virus particle, was also
      enhanced by RA. This effect does not appear to require N-myc amplification in the
      target NB cells since RA had similar effects upon the high N-myc (IMR-32) and the
      low N-myc expressing cells (SK-N-SH). Enhanced sialylation has been shown by
      others to mediate the growth inhibitory effects of RA on a variety of tumor
      lines. Removal of sialic acid from the IMR-32 NB cell surface using Clostridium
      neuraminidase (2.7 mg/mL) inhibited 75% of NDV plaque formation. These results
      demonstrate that NDV killing of two NB cell lines is enhanced using clinically
      achievable levels of RA and that sialylation of the NB cell surface is important
      for virus binding and cytotoxicity.

PMID- 8263679
TI  - Hyaluronate metabolism undergoes an ontogenic transition during fetal
      development: implications for scar-free wound healing.
AB  - Wound healing in the fetus occurs by a different process from that in the adult.
      Instead of healing with scar formation, fetal cutaneous wounds heal by
      regeneration that results in complete restoration of normal skin architecture.
      The mechanisms responsible for this remarkable phenomenon involve factors in the
      fetal environment and properties intrinsic to fetal cells. Hyaluronic acid (HA)
      is a major component of the fetal extracellular matrix (ECM) and is believed to
      play an important role in this process. In this study, HA and HA-stimulating
      activity (HASA) in fetal and adult wound fluid were examined using sensitive,
      newly developed assays. In an ovine model, higher levels of HA and HASA were
      observed in fetal as compared with adult wound fluid. This difference was most
      prominent in wound fluid from fetal lambs at 75 and 100 days gestation (term =
      145 days); these samples contained persistently elevated HA and HASA levels for
      up to 2 weeks after wounding (HA peak levels 145 micrograms/mL and 110
      micrograms/mL, respectively). In contrast, wound fluid from 120-day-gestation
      fetuses had significantly lower levels (P < .001) that were transient and similar
      to that in the adult (HA peak levels 70 micrograms/mL and 10 micrograms/mL,
      respectively). These observations confirm an ontogenic transition in wound HA
      metabolism from a fetal to an adult-like phenotype. Levels of HASA as a function
      of time after wounding correlated with levels of HA, suggesting a role for HASA
      in controlling HA deposition during tissue repair. Two patterns of HASA and HA
      synthesis were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263680
TI  - Effect of transamniotic administration of epidermal growth factor on fetal rabbit
      small intestinal nutrient transport and disaccharidase development.
AB  - As fetal swallowing is documented in utero, supplementation of the ingested
      amniotic fluid with nutrients or hormones has been postulated as a potential
      prenatal treatment for intrauterine growth retardation (IUGR). To study the
      effect of epidermal growth factor (EGF) on the developing fetal small intestine,
      12 pregnant rabbits underwent operation on day 24 of a normal 31-day gestation.
      Bilateral ovarian end fetuses underwent catheterization of their respective
      amniotic cavities with attachment to a miniosmotic pump. Study fetuses received
      recombinant human EGF at approximately 300 micrograms/kg/d for 1 week; controls
      received carrier solution only at an equivalent rate. On gestational day 31,
      fetuses were delivered by cesarean section and somatic measurements were
      recorded. The small intestine was harvested and proximal, middle, and distal
      regions were analyzed for lactase and maltase enzyme activity. Additionally, the
      uptake of radiolabeled glucose and proline was measured by a standard everted
      mucosal sleeve technique for each segment. Results were analyzed by Student's
      paired t test and reported as mean +/- SEM. Nine fetal pairs survived (75%).
      Small intestinal (SI) length was increased in EGF fetuses (54.8 +/- 1.9 cm)
      versus control (50.4 +/- 2.7 cm) (P = .02). Lactase activity, reported as UE/g
      protein, was significantly increased in the proximal segments in the EGF-infused
      fetuses; maltase was significantly increased in both the proximal and middle
      segments (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263681
TI  - A rational approach to the use of fine-needle aspiration biopsy in the evaluation
      of primary and recurrent neoplasms in children.
AB  - Fine-needle aspiration (FNA) has been recommended as a technique for accurate
      evaluation and diagnosis of childhood malignancies. Very little data exist
      regarding the limitations and utility of FNA in children. We reviewed our
      experience over the past 5 years to assess the clinical use of FNA and its
      limitations. One hundred seventy-three FNAs were performed in 156 patients who
      ranged in age from 7 months to 18 years. Sixty-three patients were female and 110
      were male. Thirty-seven aspirations were obtained to evaluate new masses in
      children with previously diagnosed malignancies. FNA allowed diagnosis of the
      malignancy in 90% of patients with solid tumors, whereas only 9 of 19 patients
      with lymphomas were diagnosed accurately with FNA. The specificity was 99.7%.
      Inadequate material was obtained in 13 aspirates. Insufficient material was
      obtained in 14% of patients who had FNA as their initial diagnostic tool. Four
      false-negatives were obtained while evaluating children for recurrent disease.
      There were 16 true-negative biopsies. These data suggest that FNA is an excellent
      tool for diagnosing both recurrent malignancies as well as previously undiagnosed
      solid tumors in the pediatric population but is inadequate to diagnose children
      with suspected undiagnosed lymphomas. Negative studies should be considered
      nondiagnostic and followed by open biopsies when clinical suspicion of malignancy
      is high.

PMID- 8263682
TI  - Routine total bilateral adrenalectomy is not warranted in childhood familial
      pheochromocytoma.
AB  - The surgical management of familial childhood pheochromocytoma is based on data
      derived from clinical series that have focused primarily on the multiple
      endocrine neoplasia (MEN)-associated cases. Prophylactic bilateral total
      adrenalectomy has been advocated for this group due to a high incidence of
      bilateral adrenal involvement and the propensity for tumor recurrence after
      partial adrenal resections. We retrospectively reviewed our experience with a
      cohort of children with nonsyndromatic familial pheochromocytoma to see if their
      surgical management should parallel that advocated for patients with the MEN
      syndrome. From 1977 through 1991, 17 children from 9 families with a strong
      family history of pheochromocytoma were treated at the Children's Hospital of
      Pittsburgh. None of the patients or their families displayed an association with
      the MEN syndrome. There were 13 males and 4 females with a mean age of 10.1
      years. Follow-up was obtained on all patients and averaged 6 years. All tumors
      were located within the abdominal cavity. Seven patients presented with
      unilateral adrenal tumors while four patients had synchronous bilateral tumors.
      Eight patients had tumors in extra-adrenal locations; 2 with concomitant adrenal
      tumors. Ten patients underwent total unilateral adrenalectomy with or without
      resection of extra-adrenal tumor(s). All patients with synchronous bilateral
      adrenal tumors underwent unilateral adrenalectomy in combination with a partial
      contralateral adrenal resection without a recurrence after an average of 7.3
      years. Three patients developed metachronous adrenal tumors an average of 4.2
      years after their initial surgery. All required complete removal of the affected
      adrenal, resulting in two patients with bilateral adrenalectomies.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8263683
TI  - The metabolic response to operative stress in infants.
AB  - The aim of this study was to characterize energy metabolism and substrate
      utilization in infants following an operation. Nineteen infants (weight 3.2 +/-
      0.2 kg) who had an operation were studied. Anesthesia was standardized and
      operative stress score (OSS) was recorded. Five infants had a minor operation
      (OSS < 7), and 14 infants had a major operation (OSS > or = 7). Energy and
      nitrogen intake were constant during the 48-hour study period. Respiratory gas
      exchange was measured by indirect calorimetry preoperatively, and postoperatively
      for the first 12 hours continuously and at 24 hours, 48 hours, and 5 days.
      Urinary nitrogen excretion rate was measured for the first 48 hours following the
      operation. Physical activity was scored. Resting energy expenditure (REE) and
      nonprotein respiratory quotient (NPRQ) were calculated. REE increased
      postoperatively, peaking at 2 to 4 hours, and returned to baseline levels by 12
      to 24 hours. Peak REE was significantly higher than baseline REE (P < .001).
      Substrate utilization was not altered by operation. The increase in REE was
      significantly greater in infants having a major operation than in infants having
      a minor operation (P < .05). Among infants having a major operation, the increase
      in REE was significantly greater in those infants more than 48 hours old, than in
      those infants less than 48 hours old (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263684
TI  - Recombinant tissue plasminogen activator for neonatal and pediatric vascular
      thrombolytic therapy.
AB  - Thrombotic vascular occlusion may complicate the clinical course of many neonatal
      and pediatric pathologic processes. Systemic thrombolytic therapy with heparin,
      urokinase, or streptokinase may not be appropriate in the critically ill neonate
      because these agents generate a diffuse coagulopathic state. Direct surgical
      intervention for repair may be precluded by the small size of the vessels
      involved. Recombinant tissue plasminogen activator (rTPA) induces only a minimal
      proteolytic state while inducing thrombolysis within the local environment of the
      clot. We report our experience with regional rTPA infusion in four critically ill
      patients with venous and arterial thrombotic disorders. there were two brachial
      artery occlusive lesions--a neonate with iatrogenic occlusion due to a misplaced
      intravenous catheter and a 2-year-old child with inadvertent arterial ligation
      during an attempted venous cutdown. Two venous lesions consisted of a full-term
      neonate with renal vein/inferior vena caval thrombosis and a 32-week infant with
      partial superior vena caval thrombosis due to a Broviac catheter. Systemic
      thrombolytic therapy was contraindicated in these patients because of underlying
      illnesses. Pretherapy vascular evaluation included Doppler examination and
      angiography. The rTPA infusion was continued until there was evidence of clot
      lysis by ultrasound, angiogram, or venogram. Infusion rate of rTPA was adjusted
      according to fibrinogen levels. All three neonates responded successfully to rTPA
      therapy. Two neonates required only bolus administration and one responded to
      combined bolus and continuous infusion therapy after 58 hours. rTPA failed to
      reverse brachial artery occlusion in the 2-year-old child with purpura
      fulminans.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263685
TI  - Total parenteral nutrition-associated cholestasis: clinical and histopathologic
      correlation.
AB  - Cholestatic jaundice is the major complication of total parenteral nutrition
      (TPN) in infants and children. The pathogenesis of this syndrome is poorly
      understood. The aims of this study were: (1) to define the histologic liver
      injury in relation to the clinical course of infants on TPN and (2) to determine
      whether enteral feeding will reverse or halt these changes. We identified 31
      infants treated for severe gastrointestinal disease for whom liver histology was
      available from 1987 to 1991. Clinical records and liver biopsy (23) or autopsy
      specimens (13) were reviewed. Five patients had biopsies at two subsequent
      operations. The clinical diagnosis was necrotizing enterocolitis (24), atresia or
      stenosis (3), midgut volvulus (2), Hirschsprung's disease (1), and sepsis (1).
      Twenty-one of 31 infants were premature and had a mean birth weight of 1,868 g.
      Twenty-five of 31 were on TPN and 28 of 31 had received some enteral feeding by
      the time of the biopsy. Enteral feeding was begun as early as possible in all
      infants even if continued TPN was necessary for full support. Cholestasis
      occurred in 71% of premature infants versus 22% of full-term babies. Infants with
      cholestasis had been on TPN for a longer time (37 days v 18) with a
      correspondingly shorter period of enteral feeding (17 days v 27). Mean total
      bilirubin level was 14 in patients with cholestasis and 5 in those without, but
      the bilirubin level did not correlate with the extent of histological injury and
      was frequently normal despite marked histological damage.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8263686
TI  - Feeding Roux-en-Y jejunostomy in the management of severely neurologically
      impaired children.
AB  - Feeding problems are legion in severely neurologically impaired children. Many
      patients do well with a gastrostomy with or without fundoplication.
      Unfortunately, fundoplication is not without complication, emphasizing the need
      for other options in the management of these difficult patients. Since 1990 six
      patients (age range, 2 months to 6 years) have been treated by the creation of a
      permanent Roux-en-Y end-jejunostomy and a gastrostomy. The Roux limb is closed
      tightly around a mushroom catheter. The gastrostomy is left for gastric
      decompression, and the jejunostomy tube is used for all nutrition and most
      medications. One patient died in the postoperative period. All the others have
      done well, without significant complication and with a high level of parent
      satisfaction (average follow-up, 12 months). Previously four other patients were
      treated with a Roux-en-Y jejunostomy in which, rather than closing the Roux limb
      around the catheter, it was brought out as a catheterizable stoma. Frequent
      leakage and prolapse make this approach less desirable.

PMID- 8263687
TI  - Intestinal rotation and fixation abnormalities in heterotaxia: early detection
      and management.
AB  - Intestinal rotation and fixation abnormalities (IRFA) are known to coexist with
      heterotaxia (defined as an abnormal arrangement of body organs that is different
      from complete situs solitus or complete situs inversus), but little is known
      about the incidence of this association or its clinical management. We have
      reviewed the records of 34 patients diagnosed with heterotaxia during a 12-year
      period at Yale-New Haven Hospital in order to develop a plan for the early
      diagnosis of IRFA and to assess the value of preventive treatment in this
      complicated group of patients. Of the 34 patients with heterotaxia, all except
      one presented with complex congenital heart disease. The 34 patients were divided
      into two groups on the basis of their gastrointestinal workup for suspected IRFA.
      The 28 patients in group A had no upper gastrointestinal (GI) contrast study
      performed prior to symptoms suggestive of IRFA. Four of these 28 patients (14%)
      eventually developed complications of IRFA requiring emergency surgery. Group B
      consisted of six patients seen during the past 5 years with heterotaxia who had
      upper GI contrast studies while asymptomatic. All six (100%) were shown to have
      IRFA and subsequently underwent an uncomplicated elective Ladd procedure once
      their cardiac condition stabilized. This study confirms the high incidence of
      IRFA in patients with heterotaxia. We propose that evaluating patients with
      heterotaxia syndrome for IRFA while asymptomatic may prevent the need for
      emergency abdominal surgery in patients that have major cardiovascular anomalies.

PMID- 8263688
TI  - Familial Hirschsprung's disease: 20 cases in 12 kindreds.
AB  - This report describes 20 infants and children with a family history of
      Hirschsprung's disease in 12 kindreds. A total of 260 patients were treated for
      Hirschsprung's disease (1972 to 1991), yielding a familial incidence of 8%. There
      were no families with consanguineous marriage. Sixteen patients were male and
      four were female. The mean age at diagnosis was 18 days. Clinical presentation
      included delayed passage of meconium in 15, abdominal distention in 11, vomiting
      in 9, feeding abnormalities in 3, and complete bowel obstruction in 1. Associated
      congenital anomalies occurred in 25% of the patients. The extent of aganglionosis
      was rectal in 4, sigmoid in 4, left colon in 2, transverse or right colon in 2,
      and total colonic in 8. Enterocolitis occurred in 7 patients (35%); 2 at
      diagnosis, 2 after an ostomy, and 3 after a pull-through procedure. There were no
      deaths associated with enterocolitis. All patients had a proximal diverting
      colostomy or ileostomy, and 19 of 20 underwent a definitive pull-through
      procedure. Three patients were lost to follow-up and one patient died of
      complications of multiple congenital anomalies unassociated with Hirschsprung's
      disease. Of the remaining 16 patients, all of whom have undergone a pull-through
      procedure, 11 are fully continent, 2 have nighttime soiling, 2 are too young to
      evaluate bowel function, and 1 still has an ostomy.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263689
TI  - Hirschsprung's disease: three decades' experience at a single institution.
AB  - Experience with 250 patients treated for Hirschsprung's disease over the past
      three decades shows several interesting features. Only 58% had rectosigmoid
      disease. Twenty-six percent had long-segment disease, and 12% had total colon
      aganglionosis. This distribution did not change significantly over the decades.
      The male:female ratio was 3.3 in all groups, but dropped to 2.2 with total colon
      disease. The mean age at diagnosis decreased from 18.8 months during the 1960s to
      2.6 months in the 1980s. The mean age at which the pull-through procedure was
      performed also dropped from 34 months to 15 months. Twenty-three patients died:
      17 in the 1960s and three in each of the succeeding decades. The Swenson
      procedure was predominant during the 1960s, but was only 2% of the pull-throughs
      in the 1980s. The endorectal pull-through increased from 22% in the 1960s to 71%
      in the 1980s. In the 1970s and 1980s the Duhamel accounted for 26% of the pull
      throughs. With a mean follow-up of 51 months, the mean number of episodes of post
      pull-through enterocolitis per patient was 0.53. This increased from 0.44 in the
      1960s, to 0.52 in the 1970s, to 0.67 in the 1980s. The incidence of post-pull
      through enterocolitis increased somewhat with the length of the bowel involved,
      and was greatest with the Duhamel (0.95 episodes per patient), less with the
      Swenson (0.60), and least with the endorectal pull-through (0.38). In contrast,
      the incidence of complications other than enterocolitis was greatest with the
      Swenson (20%), less with the endorectal pull-through (17%), and least with the
      Duhamel (13%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263690
TI  - The epidemiology of injury in a rural state: 5,322 cases over 6 years.
AB  - Presently, descriptions of rural trauma are complications of national sample
      statistics and local data from states projected to rural areas. This study
      reviews all hospital discharges (36,866) for children (aged 0 to 18 years) from
      January 1985 through December 1990 in an entirely rural state. Fourteen percent
      of admissions (5,322) were due to traumatic injury and 63% of these occurred in
      boys. Injury rates were age dependent with children 15 to 18 years experiencing
      an incidence of 110/10,000; 10 to 14 years 55/10,000; 5 to 9 years 39/10,000; 1
      to 4 years 35/10,000; and < 1 year 39.5/10,000. Mean age for the entire
      population was 11.4 +/- 5.7 years. Thirty-five percent of children had more than
      one major site of injury. Sixty-three percent of admissions were for blunt trauma
      and only 4.8% were penetrating. The remainder were due to burns, hanging,
      ingestion, and other toxic agents. Falls constituted the most prevalent cause of
      injury in this population occurring in 25.9%, motor vehicle accidents 22.9%,
      struck by an object 9.6%, suicide attempts 8.5%, poisoning 4.7%, fire 1.2%,
      drowning 0.7%, and farm machinery 0.3%. The vast majority of motor vehicle
      accidents involved the child as an operator or occupant of the vehicle. Less than
      10% involved a pedestrian being struck and less than 5% involved a child being
      struck while on a bicycle. Less than 6% of all injuries involved a bicycle. Child
      maltreatment was recorded in less than 2% of this population. Only 3.3% of
      injured children required transfer to another acute care facility (1/3 because of
      a motor vehicle accident and 1/4 because of a fall).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263691
TI  - Reperfusion injury following single-lung transplantation: the tissue glutathione
      response.
AB  - Parenchymal injury following reperfusion of the donor lung remains a significant
      problem in clinical lung transplantation. It has been postulated that free oxygen
      radicals act as local mediators of this event, and that tissue oxidized
      glutathione levels which reflect local free oxygen radical production, may be
      useful as an indicator of this regional ischemia-reperfusion injury. The
      glutathione redox cycle plays a physiologically important role in the endogenous
      antioxidant defense system. Intracellular glutathione depletion has been shown to
      render cells vulnerable to oxidant mediated injury. Adequate glutathione stores
      may be vital in protecting the cell from oxidant injury, especially the
      relatively exposed pulmonary epithelial cells. Single lung transplantation was
      carried out in 10 3- to 5-kg mongrel puppies, with a standard 2-hour ischemic
      time for the donor lung prior to reimplantation. Four hours following
      transplantation, lung tissue was harvested from both the transplanted and native
      lung of the recipient animal, and compared to normal lung tissue from the donor
      animal. Tissue was prepared for histological evaluation and glutathione assay.
      Tissue glutathione levels were determined via a spectrophotometric assay. For
      determination of oxidized glutathione (GSSG), samples were prepared with 2
      vinylpyridine and N-ethylmaleimide (NEM) to derivatize all reduced glutathione
      and leave only GSSG for measurement by the fluorometric assay.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8263692
TI  - Survival after reduced-size liver transplantation is dependent on pretransplant
      status.
AB  - Orthotopic liver transplantation (OLT) in children is characterized by unique
      problems including a shortage of compatible-size donors resulting in long waiting
      periods, significant deterioration while waiting, and death before
      transplantation. To improve the chances of obtaining an organ for the sickest
      patients, reduced-size liver transplantation (RSLT) was offered to all hospital
      bound children starting in July 1988. Since then, 68 OLTs were performed in 58
      children. Thirty-six RSLTs were done in 30 children (42% of total 86 OLT, 53%
      since 1988). The mean weight of the RSLT patients was 13.5 +/- 10.4 kg versus
      23.8 +/- 21.9 kg in the full-size (FSLT) group (P < .05). Twenty-five of 39
      transplants (71.4%) done in children < 10 kg were RSLTs in comparison to only 10
      of 47 (21.3%) in patients > 10 kg (P < .0005). Since 1988, 25 of 34 (73.5%) of
      all transplants in children < 10 kg have been RSLTs. Average donor to recipient
      weight ratio in the RSLT group was 4.21:1 versus 1.17:1 in the FSLT group (P <
      .0001). RSLT was done as a primary procedure in 26 patients and as a retransplant
      in 10. Mean blood product replacement was significantly higher in the RSLT group
      both intraoperatively (515.7 +/- 490.9 v 177.2 +/- 278.3 mL/kg, P < .005) and
      during the first 24 hours postoperation (50.5 +/- 81.8 mL/kg v 16.4 +/- 28.5
      mL/kg, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263693
TI  - Isolated fetal mouse limbs: gestational effects on tissue repair in an unperfused
      system.
AB  - While it is known that adult tissue repair is tightly regulated through local
      effects in the wound environment mediated by circulating blood elements such as
      platelets, white cells, cytokines, and hormones, the degree to which each is
      required in fetal tissue repair is uncertain. This raises the following questions
      regarding regulation of fetal tissue repair: (1) is the local wound matrix alone
      sufficient to sustain fetal tissue repair in the same regenerative manner seen in
      previous in vivo whole animal studies? (2) Will it occur only during the period
      of rapid fetal growth and development in early and mid gestation? To address
      these fundamental questions, an organ culture system has been designed to grow
      isolated, unperfused, developing fetal mouse limbs in a chemically defined, serum
      free media. Amputated fetal mouse forelimbs (n > or = 10) were wounded with
      linear incisions at gestational days 14, 16, and 18 (term = 19); the wounds were
      closed primarily. These amputated and wounded limbs were placed on steel grids in
      organ culture petri dishes, then partially submerged in a chemically defined,
      serum-free media. The limbs were grown at 37 degrees C in humidified 95% air/5%
      CO2 for 1 week. These wounded limbs were examined histologically at days 0, 3,
      and 7 postwounding to determine their viability and whether or not tissue repair
      occurred. In the 14-day group, limb growth and differentiation was evident during
      the incubation period. Normal dermal and epidermal architecture was restored at
      the wound site without abundant collagen deposition by day 7
      postwounding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263694
TI  - The potential role of the lymphocyte in fetal wound healing.
AB  - Wound healing is a complex process involving a number of different cell
      populations. Since fetal wounds contain only a small number of mononuclear cells
      and no fibrosis immunohistochemical techniques using monoclonal antibodies
      specific to T and B lymphocytes, as well as macrophages, were used to identify
      the mononuclear cells in fetal wounds and to compare the lymphocyte response with
      the adult wound healing response. Polyvinyl alcohol sponges were placed
      subcutaneously in fetal rabbits on day 24 of gestation (then 31 days). Adult
      rabbits underwent similar implantation. Implants (8 to 14 per group) were
      harvested 5 days later and examined by H&E and trichrome staining as well as
      immunohistochemical staining with monoclonal antibody (Mab) specific for rabbit T
      and B lymphocytes. The sponges in one group of fetal rabbits were impregnated
      with the polypeptide growth factor, transforming growth factor-beta (TGF-beta), a
      known regulator of adult tissue repair. Adult wounds showed an intense
      inflammatory response with extensive collagen deposition; 80% of the infiltrating
      cellular elements were T lymphocytes. Fetal wounds were less cellular with
      minimal collagen deposition; 40% of the cells were T lymphocytes. The fetal
      wounds treated with TGF-beta were intensely cellular and fibrotic with 71% of the
      cellular infiltrate comprised of T lymphocytes. The increased cellularity of the
      TGF-beta wounds appears to be primarily the result of increased numbers of T
      lymphocytes. These findings demonstrate that the fetus mounts an attenuated T
      lymphocyte response compared to the adult. The increased response of T
      lymphocytes with TGF-beta suggests that the specific growth factor milieu may
      account for the fetal response to wounding.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263695
TI  - Disappearing fetal lung lesions.
AB  - Cystic adenomatoid malformations and sequestrations of the lung are uncommon but
      potentially devastating problems of the fetus and neonate. We have followed over
      50 cases of fetal lung masses from the time of prenatal diagnosis. Serial
      prenatal ultrasonography demonstrated that 9 large pulmonary lesions dramatically
      decreased in size or disappeared completely. We conclude that the natural history
      of prenatally diagnosed fetal lung masses is highly variable. A huge mass
      associated with fetal hydrops has a dismal outcome. If hydrops is not present,
      then the initial impression concerning prognosis may not accurately predict
      outcome, because there may be marked improvement during fetal life.

PMID- 8263696
TI  - Mortality and respiratory failure in a pediatric burn population.
AB  - A 9-year retrospective review of 1,242 admissions to a tertiary burn center
      identified 137 patients who were intubated and ventilated for a critical airway
      or pulmonary problem. These patients varied in age from 2 months to 18 years with
      an average total body surface area (TBSA) burn of 55%. We evaluated this group
      for evidence of respiratory failure (ARF) as defined by the respiratory failure
      index (RFI) (PaO2/FIO2 < or = 300). While only 23% of admissions to the burn
      center were related to flame burns, these injuries accounted for 82% of children
      who had ARF. Forty-two percent of these intubated children had abnormalities on
      their admission chest x-ray and 61% of this cohort developed evidence of ARF as
      defined by the RFI. The development of sepsis along with ARF regardless of TBSA
      involvement doubles the mortality of ARF alone. Early burn wound excision and
      grafting is critically important to prevent the late complication of sepsis. We
      carefully monitor ventilator settings to insure low peak inspiratory pressures,
      allowing relative hypercapnia and avoiding hyperoxia. Despite an increased number
      of admissions and critically injured children, we have not seen an increase in
      morbidity and have had a 53% reduction in mortality in the last 2 years with
      these techniques. We believe this management offers the best outcome for the
      pediatric burn victim and would recommend this strategy to other centers dealing
      with these severely injured children.

PMID- 8263697
TI  - Decreased incidence of intracranial hemorrhage using cephalic jugular venous
      drainage during neonatal extracorporeal membrane oxygenation.
AB  - Intracranial hemorrhage (ICH) remains one of the more common serious
      complications of extracorporeal membrane oxygenation (ECMO) in neonates. In 1990
      this center began routine use of cephalic jugular venous drainage during neonatal
      ECMO to augment blood return to the ECMO pump and potentially decrease the
      incidence of ICH by decreasing cerebral venous pressure. Thirty-four ECMO cases
      utilizing cephalic jugular venous drainage were compared with the previous 34
      ECMO cases. The incidence of ICH decreased from 35% (12/34) to 6% (2/34) when
      neonates without cephalic jugular venous drainage are compared with those being
      subject to this technique (P < .01). No differences were found between the two
      groups in gestational age, birth weight, duration of ECMO, survival, platelet
      counts, activated clotting times, or incidence of other bleeding complications.
      Cephalic jugular venous drainage during neonatal ECMO appears to be safe and may
      decrease the incidence of ICH.

PMID- 8263698
TI  - The efficacy of extracorporeal life support in premature and low birth weight
      newborns.
AB  - Based on data obtained early in the development of neonatal extracorporeal life
      support (ECLS), contraindications to the use of ECLS have included low estimated
      gestational age (EGA) and low birth weight (BW). However, multiple improvements
      in the technical and management aspects of neonatal ECLS have been implemented
      since those early data were evaluated. The purpose of this study, therefore, is
      to assess in the "modern era" the efficacy of prolonged extracorporeal support in
      premature and low birth weight newborns. Examination of the Extracorporeal Life
      Support Organization (ELSO) Registry showed that between 1988 and 1991 ECLS was
      utilized in 158 premature (PREM, EGA < or = 34 weeks), 4,128 full-term (FT, EGA >
      or = 35 weeks), 26 low birth weight (LBW, BW < 2.0 kg), and 4,333 normal birth
      weight (NBW, BW > or = 2.0 kg) patients with respiratory failure. Data were
      evaluated for variables thought to be associated with a decrease in survival or
      an increase in the incidence of intracranial hemorrhage (ICH). A logistic
      regression model was developed to evaluate the ability of EGA and BW to predict
      survival. The incidence of survival (SURV) was decreased (63% v 84%) and ICH
      increased (37% v 14%) significantly in PREM when compared with FT newborns (P <
      .001). However, respectable survival rates in PREM patients with EGA > 32 weeks
      were documented. In addition, both survival and ICH in PREM patients have
      improved substantially when compared with past reports (Past: SURV = 25% and ICH
      = 100%; current: SURV = 63% and ICH = 37%; ICH P < .001; SURV P = .056). Survival
      was significantly decreased in LBW when compared to NBW neonates (65% v 83%, P <
      .05), but there was no significant difference in ICH.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263700
TI  - A 25-year experience with renal tumors of childhood.
AB  - A retrospective analysis of the medical records of 234 children with renal tumors
      managed over a 25-year period at the Children's Memorial Medical Center was
      undertaken to evaluate long-term morbidity and mortality. There was a significant
      increase in survival over the years of the study. The 5-year survival for
      patients treated during the period 1985 to 1989 was 94% versus 68% for the period
      1965 to 1969. Thirty-three children have died, 15 with known disease progression.
      Long-term morbidity included scoliosis (39), cardiorespiratory insufficiency
      (13), hypertension (7), renal insufficiency (7), small bowel obstruction (10),
      chest wall deformity (3), amenorrhea (1), leg length discrepancy (1), and 1
      patient with an esophageal stricture. One patient with cardiomyopathy secondary
      to adriamycin has recently undergone cardiac transplantation. Five patients with
      renal insufficiency have required dialysis. Of these five, one patient has had
      two renal transplants. The presence of distant metastases and positive hilar or
      regional lymph nodes were the only findings at operation that were associated
      with an increased mortality (P = .005). There was a significantly increased
      mortality in those children operated on by general surgeons or urologists at
      other hospitals (11/43) versus those operated upon at our hospital (22/191) (P =
      .033). There was no statistical difference in the staging or histology among
      these children. We feel that the careful and systematic approach of a radical
      nephrectomy assures accurate staging of the tumor removing gross and microscopic
      disease in the abdomen.

PMID- 8263699
TI  - Forty-year experience with second malignancies after treatment of childhood
      cancer: analysis of outcome following the development of the second malignancy.
AB  - As the cure rate for childhood malignancies increases, the number of patients at
      risk for development of second malignancies also increases. Due to the
      potentially long remaining life span, long-term follow-up is difficult and
      patients are often at risk after presumptive cures. Some authors believe that
      cure rates for second malignancies are similar to cure rates for primary
      malignancies. We reviewed the records of 162 patients seen at our institution who
      had developed a second malignancy after treatment for childhood cancer.
      Presentation, age at diagnosis, tumor histology, extent of tumor, treatment
      (including radiotherapy with dosage when available, and chemotherapy) plus
      outcome were recorded. Mean age at diagnosis of the primary malignancy was 10.3
      years. The most common primary malignancy was Hodgkin's disease (33) followed by
      soft tissue sarcoma (28), retinoblastoma (20), bone tumor (17), central nervous
      system (CNS) tumor (13), leukemia (8), Wilms' tumor (7), non-Hodgkin's lymphoma
      (6), neuroblastoma (5), thyroid neoplasm (5), and others (20). The average
      interval between diagnosis of the first and second malignancy was 10.8 years.
      These second tumors carried a high mortality. Only 56 patients have no evidence
      of disease. Five patients are known to be alive with disease and 92 patients have
      expired due to their second malignancy. Disease status in 8 patients is unknown.
      The most common second malignancy was osteosarcoma (35) followed by soft tissue
      sarcoma (24), breast cancer (15), leukemia (14), thyroid carcinoma (14), CNS
      tumors (12), melanoma (8), nonmelanomatous skin cancer (8), lymphoma (5), and
      others (27).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263701
TI  - Successful management of an infant with a giant hemangioma of the retroperitoneum
      and Kasabach-Merritt syndrome with alpha-interferon.
AB  - Giant vascular neoplasms in neonates generally require aggressive medical or
      surgical therapy for treatment of complications. Steroids, chemotherapy,
      embolization, radiation, and surgery have all been used with short-term
      beneficial and sometimes unknown long-term side effects. A new modality of
      treatment, alpha-interferon, has recently been described. The majority of
      hemangiomas in children involute by 8 years of age. Occasionally, hemangiomas can
      endanger vital structures and are associated with a consumption coagulopathy and
      thrombocytopenia (Kasabach-Merritt Syndrome). These hemangiomas occasionally do
      not respond to steroids, radiation therapy, cytotoxic drugs, or embolization. The
      mortality rates approach 50% in nonresponders. Alpha-interferon has been used in
      these children with life-threatening complications of hemangiomas with relief of
      symptoms. This case illustrates the potential use of alpha-interferon in the
      management of giant hemangiomas in children. This emerging form of biological
      therapy avoids the risks of radiation therapy, embolization, and surgery with
      only minimal side effects.

PMID- 8263702
TI  - Cloacal exstrophy: experience with 20 cases.
AB  - Exstrophy of the cloaca, a rare anomaly, is among the most complex malformations
      of infancy. Features include omphalocele, imperforate anus, and exstrophy of two
      hemibladders, between which lies the everted cecum. A small colon ends blindly in
      the pelvis, and the terminal ileum often prolapses out of the exposed cecum.
      Formerly, most of these infants died. From 1974 to 1992, 20 of these patients
      were treated, the majority in the past decade. Six were managed primarily; 14
      were referred after prior surgery elsewhere. Current treatment of a newborn with
      cloacal exstrophy includes closure of the omphalocele, separation of the gastro
      intestinal tract from the hemibladders, and closure of the two hemibladders as a
      single viscus. The colon can be pulled through in some cases, either immediately
      or later (6 cases). The bladder must be augmented in all cases to provide
      adequate volume and compliance; stomach is ideal for this (10 cases). A bladder
      continence mechanism must be constructed by narrowing the outlet (9 cases), or
      inserting a reversed small bowel nipple (7 cases). Intermittent catheterization
      is needed for the patient to empty the reconstructed bladder. Although two thirds
      of these patients are genetic males, they should be raised as females because
      they lack adequate tissue to construct a phallus. Magnetic resonance imaging of
      the spine has shown tethering of the cord in all patients; most were released
      neurosurgically. Lessons provided by these cases demonstrate that a satisfactory
      surgical and social outcome can be achieved today in most children with cloacal
      exstrophy.

PMID- 8263703
TI  - Bladder pressure monitoring significantly enhances care of infants with abdominal
      wall defects: a prospective clinical study.
AB  - Increased intraabdominal pressure (IAP) has been demonstrated to cause intestinal
      and renal ischemia in both animals and humans. Neonates undergoing closure of
      anterior abdominal wall defects are at risk for these complications from markedly
      increased IAP, which are putatively responsible for a 13% to 20% mortality. In an
      effort to decrease morbidity and mortality we performed a 4-year prospective
      clinical study to determine if monitoring IAP using bladder pressure (BdP)
      measurements would significantly improve perioperative care in infants with
      abdominal wall defects. Forty-two consecutive infants with gastroschisis (28) and
      omphalocele (14) were prospectively studied. Intraoperative and serial
      postoperative measurements of BdP were obtained from an indwelling bladder
      catheter using a standard pressure transducer. Methods of initial closure, as
      well as manipulations in sedation, paralysis, and silo reduction, were selected
      to keep BdP < 20 mm Hg. Bladder pressure monitoring significantly altered the
      management of 64% of our patients, particularly those with gastroschisis (74%).
      Thirteen patients with gastroschisis underwent staged closure; in 7 (54%) this
      decision was based on high BdP even though bowel reduction was mechanically
      possible. Elevated BdP influenced the closure method and timing of silo
      reductions in 5 of 14 (42%) infants with omphalocele. There were no episodes of
      renal failure or refractory oliguria. There were three patients in a single
      cluster who developed uncomplicated, nonsurgical necrotizing enterocolitis late
      in their respective courses. One patient whose bowel was placed in a silo had
      severe hypotension associated with group B streptococcal sepsis and subsequently
      developed necrotic bowel despite low BdP.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263704
TI  - Muscle pH/PCO2 monitoring.
AB  - The surface pH of skeletal muscle has been confirmed to be a sensitive indicator
      of peripheral muscle blood flow, but the development of a better electrode has
      been required. As a consequence, a unique and minute sensor was developed to
      measure muscle pH/PCO2. The purpose of this article was to evaluate this new
      monitoring device experimentally and clinically in order to clarify its effects,
      usefulness and specificity. Our experimental and clinical results showed that
      placement and measurements using the muscle pH/PCO2 monitor were easily and
      quickly accomplished without any complications. This small sensor provided an
      accurate assessment of vital physiologic functions and gave an early warning of
      clinical deterioration. The new monitor should be useful in pediatric surgery
      clinical management.

PMID- 8263705
TI  - Mucosal permeability in the immature rat intestine: effects of ischemia
      reperfusion, cold stress, hypoxia, and drugs.
AB  - Increased mucosal permeability may represent an important factor in the etiology
      of necrotizing enterocolitis (NEC). In the present study we used an immature rat
      model to assess the permeability effects of a number of stresses commonly seen in
      infants with NEC. In 10-day-old rats, mucosal permeability to 51Cr EDTA was
      measured after subjecting the animals to 10-minute ischemia-reperfusion injury,
      30 minutes of hypoxia (14% oxygen), cold stress (4 degree C for 4 minutes), and
      intraperitoneal indomethacin (0.2 or 2.0 mg/kg) or theophylline (40 or 200
      mg/kg). When compared with appropriate controls, mucosal permeability was found
      to be significantly increased by ischemia-reperfusion injury, hypoxia, and high
      dose indomethacin, but not by cold, theophylline, or low-dose indomethacin. Renal
      clearance studies confirmed that elevated blood levels of 51Cr EDTA were due to
      increased permeability rather than decreased renal excretion of the probe. These
      studies confirm that mucosal permeability in the immature rat is increased by a
      variety of insults, and may represent a "common pathway" in the etiology of NEC.

PMID- 8263706
TI  - Simultaneous gastroesophageal pH monitoring and the diagnosis of alkaline reflux.
AB  - The diagnosis of alkaline gastroesophageal reflux (AGER) by esophageal pH
      monitoring is elusive because several other causes may raise esophageal pH above
      7. This study approaches the issue by simultaneously recording esophageal and
      gastric pH with a 2.1 mm assembly of two antimony electrodes in refluxing (n =
      69) and nonrefluxing (n = 40) children. On the basis of the information gathered,
      patients were divided into four groups: acid refluxers (GER, n = 40 or 57%),
      alkaline refluxers (AGER, n = 8 or 11%), alkalacid refluxers (AAGER, n = 15 or
      22%), and silent refluxers or false negatives (SGER, n = 6 or 9%). Children with
      AGER could not be differentiated from other refluxers nor from controls by
      esophageal pH information alone. Prolonged gastric buffering or alkalinization
      could be documented in both AGER and AAGER children, indicating extended
      duodenogastric reflux (DGR) in them. The incidence of esophagitis was not
      significantly different between the groups of refluxers: 75% for AGER and AAGER,
      73% for GER, and 67% for SGER. AGER, a disorder involving both pyloric and
      gastroesophageal barriers, is as significant a problem in children as in adults
      and may lead to severe complications even in the absence of excessive acid
      exposure. Monitoring esophageal pH alone is insufficient for making the diagnosis
      of AGER. The diagnosis can be made with little more expense and similar patient
      discomfort using the two-probe test. We suggest the need for a critical
      reassessment of the current antacid and prokinetic GER treatments and of
      antireflux operations which leave DGR intact while correcting GER.

PMID- 8263707
TI  - Simplified "push" technique for percutaneous endoscopic gastrostomy in children.
AB  - Percutaneous endoscopic gastrostomy (PEG) by the "pull" technique is the standard
      method in pediatric patients. Modifications have been reported for adults but few
      in children. Problems with the "pull" technique including pericatheter infection
      due to contamination of the tube tract with oral flora, repeated insertion of the
      endoscope, potential esophageal injury from the catheter, and the possible need
      for another endoscopy for catheter removal, prompted our interest in a simpler
      technique. The "push" technique requires insertion of the endoscope only once to
      insufflate and visualize the insertion site. A modified Seldinger technique is
      used to insert a 14F acrylic Foley catheter. We have used this technique to place
      PEG tubes in 8 children age 6 weeks to 17 years (mean, 6 years), for failure to
      thrive due to cystic fibrosis (3), neurological impairment (4), and undetermined
      cause (1). Operative time averaged 15 minutes. All PEGs were used within 24
      hours. This "push" technique of PEG insertion is safe, simple, quick, and
      obviates many of the potential risks inherent in the "pull" technique. The "push"
      technique deserves a more widespread application in children.

PMID- 8263708
TI  - Indomethacin-induced blood flow distribution in premature and full-term piglets.
AB  - Indomethacin (IND), widely used in premature infants to effect nonoperative
      closure of patent ductus arteriosus (PDA), has been implicated in
      gastrointestinal tract (GI) perforations and necrotizing enterocolitis (NEC). The
      vasoactive effects of IND could simultaneously affect regional blood flow
      distribution, specifically a decrease in intestinal blood flow. This study
      determined blood pressure (BP), heart rate (HR), cardiac output (CO), total
      peripheral resistance (TPR) and regional blood flows (mL/min/g) at baseline, 15,
      60, and 120 minutes after intravenous infusion of IND (0.4 mg/kg) in three
      groups: preterm piglets delivered 7 to 10 days before term; 1- to 2-day-old
      piglets; and 7- to 14-day-old piglets. IND did not significantly affect
      hemodynamic parameters (BP, HR, CO, TPR) or regional blood flows to the heart,
      central nervous system, kidney or GI tract in the premature animals. In 1- to 2
      day-old animals, a significant increase in BP and TPR occurred at 120 minutes,
      with significant decreases in blood flow to the GI tract in the esophagus,
      stomach, and rectosigmoid. In the 7- to 14-day group CO significantly decreased
      while TPR increased. Significant decreases in blood flow occurred throughout the
      GI tract, most pronounced in the small intestine and colon, essentially due to
      decreased mucosal blood flow. Our study indicates that indomethacin can cause
      selective GI tract mucosal ischemia, and that the effect is increased in the more
      developed animal. This effect on mucosal blood flow suggests the GI tract
      disturbances seen after IND administration are due to an ischemic injury to
      mucosa previously affected by ischemia-reperfusion injury from other stresses.

PMID- 8263709
TI  - A "smart needle" to facilitate difficult vascular access in pediatric patients.
AB  - A new Doppler probe inside a needle was evaluated in a group of infants and
      children to assess its suitability for subclavian venous access. While the
      efficient use of this device required learning a new technique, we found the
      device useful to accurately locate the subclavian vein and differentiate it from
      the artery in all patients weighing more than 3 kg. This device will be most
      helpful in cases of difficult access, eg, scar from previous access, obesity, or
      edema.

PMID- 8263710
TI  - Is early discharge following isolated splenic injury in the hemodynamically
      stable child possible?
AB  - Nonoperative treatment of splenic injury is well accepted. Two questions have not
      been answered. (1) What is the intensity of monitoring required in the
      hemodynamically stable patient? (2) How long do patients need to be hospitalized?
      Ninety-one patients having computed tomography (CT) or surgically proven splenic
      injury were treated between September 1986 and September 1991. Excluded from the
      study were 16 patients requiring operation and 22 patients having multiple system
      injuries. All operations occurred within 24 hours of admission. No transfusions
      were required later than 48 hours following admission. The remaining 53 patients
      (58%) constitute the study group. CT classification of Buntain indicated 6 class
      I, 21 class II, 24 class III, and 2 class IV injuries. The mean Injury Severity
      Score (ISS) for the group was 6.98 +/- 3.43. Serial hematocrits for the patients
      treated without transfusions were followed until three consecutive determinations
      showed no change. The lowest average hematocrit for the nontransfused group was
      30.96% +/- 4.47% and occurred on day 2.06 +/- 0.76. Eleven patients (23%) had
      left-sided pleural effusions that resolved without intervention. One patient had
      an ileus for 3 days. CT or ultrasound examination was obtained on day 5 to 7 to
      document healing before the patient was allowed out of bed and discharged. The
      average hospital stay was 7.06 +/- 2.24 days. Twenty-two patients were initially
      observed in the intensive care unit (ICU). Clearly the interval between
      hematocrit stability (average, 2.06 days) and discharge (average, 7.06 days)
      constitutes a time of minimal nursing care while utilizing bed space and health
      care dollars.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263711
TI  - Continence following electrical stimulation and EMG biofeedback in a teenager
      with imperforate anus.
AB  - A teenage boy with repaired high imperforate anus relied on daily enemas for
      social continence. After treatment with low intensity transcutaneous electrical
      stimulation and electromyographic biofeedback home programs, he achieved improved
      fecal continence requiring only one enema per month.

PMID- 8263712
TI  - Correction of congenital diaphragmatic hernia in utero: VI. Hard-earned lessons.
AB  - Extensive experimental work suggests that repair of congenital diaphragmatic
      hernia (CDH) in utero may salvage severely affected fetuses who otherwise have a
      high expected mortality despite optimal postnatal care including extracorporeal
      membrane oxygenation (ECMO). We have reported that repair of CDH in utero is
      physiologically sound and safe for the mother, but technically difficult
      especially when the liver is herniated into the fetal chest. In the 3 years since
      our last report (1989 to 1991), 61 additional patients were referred for
      consideration of in utero repair. Fetal repair was attempted in 14 with severe
      isolated left CDH diagnosed before 24 weeks gestation. Five fetuses died
      intraoperatively, from technical problems related to reduction of incarcerated
      liver and uterine contractions--problems which have subsequently been surmounted.
      Nine patients were successfully repaired. Four babies survived, two delivered
      prematurely and died, and three died in utero within 48 hours of repair.
      Intraoperative technical problems have been overcome; the factors limiting
      successful outcome are postoperative physiologic management of the maternal-fetal
      unit and effective tocolysis to control preterm labor.

PMID- 8263713
TI  - Molecular biology and life science.
AB  - Molecular biology has made the transition from phase 1, dealing with prokaryotic
      genes and DNA, to phase 2, dealing with genes of eukaryotic multicellular
      organisms. This transition came about because of the DNA technology that has
      evolved since the early 1970s. Now we are at the beginning of the transition to
      phase 3, through the emerging human genome project. The background of the
      development of this project, its current state, and its possible impact on the
      life sciences is briefly outlined and discussed.

PMID- 8263714
TI  - Regulation of Porphyromonas gingivalis virulence: hemin limitation effects on the
      outer membrane protein (OMP) expression and biological activity.

PMID- 8263715
TI  - Purification and immunolocalization of a cysteine protease from Porphyromonas
      gingivalis.

PMID- 8263716
TI  - Molecular characterization of hemagglutinin genes of periodontopathic bacteria.

PMID- 8263717
TI  - Reconstruction of severe combined immunodeficient mice with lymphocytes from
      patients with localized juvenile periodontitis.

PMID- 8263718
TI  - Neutrophil chemotaxis and serum concentration of tumor-necrosis-factor-alpha
      (TNFA).

PMID- 8263719
TI  - Evidence for a role of VLA integrins in lymphocyte-human gingival fibroblast
      adherence.

PMID- 8263720
TI  - Role of cytokines and inflammatory mediators in tissue destruction.
AB  - Colonization or emergence of microbial pathogens may result in tissue destruction
      by activation of one or more of five distinct host degradative pathways (matrix
      metalloproteinase pathway, plasminogen-dependent pathway, phagocytic pathway, PMN
      serine proteinase pathway and osteoclastic bone resorption) or by direct cleavage
      of extracellular matrix constituents by microbial proteinases. Activation of
      endogenous destructive pathways may be mediated by immune responses resulting in
      expression of degradative cellular phenotypes among both immigrant and resident
      cell populations. In addition, expression of degradative phenotypes may be
      triggered by direct influences on host cells of microbial products (LPS, enzymes,
      toxins). A body of evidence suggests that each of these mechanisms involves local
      production of proinflammatory cytokines and growth factors. The matrix
      metalloproteinase pathway is centrally involved in dissolution of all
      unmineralized connective tissues and perhaps in resorption of bone as well. The
      matrix metalloproteinase family consists of nine or more genetically distinct
      Zn++ endopeptidases which collectively cleave all of the constituents of the
      extracellular matrix. Recent studies have uncovered many essential elements of a
      complex, but still incomplete, regulatory network that governs tissue
      destruction. Proinflammatory cytokines and growth factors induce signalling
      pathways several of which are dependent on protein kinase C and result in
      transient expression of the transcription factors c-jun and c-fos. Initiation of
      transcription of most matrix metalloproteinase genes requires binding of the
      transcription factor AP-1 (c-jun/c-fos) to a specific promoter sequence but
      attainment of maximal transcription rates is dependent on interaction with other
      promoter elements as well. Several matrix metalloproteinases have been detected
      in crevicular fluids and tissues of inflamed human gingiva as have the
      proinflammatory cytokines (IL-1 and TNF-alpha) which regulate their
      transcription. Although the mere presence of enzymes and cytokines does not
      necessarily impart function per se, these observations suggest that some level of
      spatial or temporal linkage exists between metalloproteinase/cytokine expression
      and gingival inflammation.

PMID- 8263721
TI  - Detection of interleukin-8 and matrix metalloproteinases transcripts in healthy
      and diseased gingival biopsies by RNA/PCR.

PMID- 8263722
TI  - Relationship between race and lymphocyte function during acute gingival
      inflammation.

PMID- 8263723
TI  - Effects of interleukin 1 beta, tumor necrosis factor alpha and transforming
      growth factor beta on group II phospholipase A2 activity in rat gingival
      fibroblasts.

PMID- 8263724
TI  - A novel cytokine with osteoclastopoietic activity.

PMID- 8263725
TI  - New clinical diagnostic strategies based on pathogenesis of disease.
AB  - The pathogenesis of periodontal tissue destruction involves the orchestrated
      sequential activation of several components of the host response, each of which
      have the potential for providing diagnostic information regarding the health or
      disease status of the periodontium. These events include the bacterial triggering
      of serum components, the release of vasoactive compounds, the recruitment of
      inflammatory cells, the activation of phagocytes, the local secretion of
      immunoglobulins and inflammatory mediators, as well as connective tissue
      remodeling. For purposes of diagnosis, much attention has been directed toward
      the measurement of local levels of specific byproducts of the pathogenic process
      either within the tissues or in the adjacent crevicular fluid. These are site
      directed assessments of the local concentration of these byproducts, and with the
      important exception of antibody levels, very few byproducts of the periodontal
      pathogenic process have been studied on a systemic level. However, since the risk
      associated with periodontal disease progression is primarily patient-based and
      secondarily site-based, there is an increasing need to identify patients at risk
      for intervention strategies. Furthermore, there are substantial data that
      periodontal diseases are specific infections that occur in an appropriately
      susceptible host. The expression of periodontal disease has a strong genetic
      component, which presumably defines the host's response thereby affecting
      susceptibility. For this reason, there is increased interest in defining those
      elements of the host response which result in susceptibility to disease. The
      ultimate objective of a diagnostic strategy is to identify patients who are
      potentially at risk for acquiring disease to enable preventive measures.

PMID- 8263726
TI  - A stepwise approach to determine periodontal attachment loss in longitudinal
      studies.

PMID- 8263727
TI  - Use of subgingival temperature in periodontal clinical trials. Assessment of
      accuracy and reliability.

PMID- 8263728
TI  - Inflammatory mediators and immunoglobulins in GCF from healthy, gingivitis and
      periodontitis sites.

PMID- 8263729
TI  - Possible functions of human neutrophil serine proteinases, medullasin and
      cathepsin G, in periodontal tissue breakdown.

PMID- 8263730
TI  - Molecular factors regulating development and regeneration of cementum.

PMID- 8263731
TI  - Molecular and cellular interactions of a cementum attachment protein with
      periodontal cells and cementum matrix components.

PMID- 8263732
TI  - Purification and characterization of a novel growth factor from cementum.

PMID- 8263733
TI  - Regulation of differentiation of gingival fibroblasts and periodontal ligament
      cells by rhIL-1 beta and rhTNF-alpha.

PMID- 8263734
TI  - A pastor nurse responds: take steps toward healing.

PMID- 8263736
TI  - Faith and suffering.

PMID- 8263735
TI  - A nurse counselor responds: facing your pain brings healing to others.

PMID- 8263737
TI  - Singing in the face of death: bedside hymns bring hope.

PMID- 8263738
TI  - Emotional involvement: can you care without it?

PMID- 8263739
TI  - Shonie and the shootouts: when death is a daily reality.

PMID- 8263741
TI  - Spiritual distress: deciding to care.

PMID- 8263740
TI  - When a newborn cannot survive: what nurses really believe.

PMID- 8263743
TI  - Christmas in one word.

PMID- 8263742
TI  - Dorothy's unspoken Christmas hope.

PMID- 8263744
TI  - The visitor.

PMID- 8263745
TI  - I'm angry, hurt and struggling: why is God so cruel?

PMID- 8263746
TI  - A fellow sufferer responds: give yourself time to grieve.

PMID- 8263747
TI  - Alteration of in vivo cytokine gene expression in mice infected with a molecular
      clone of the defective MAIDS virus.
AB  - The discovery of T helper type 1 (Th1) and T helper type 2 (Th2) phenotypes
      within the CD4+ T-lymphocyte population has allowed for further elucidation of
      the roles the T cells play in regulation of humoral and cellular immunity. It is
      suggested that differential activation of the CD4+ subsets, particularly up
      regulation of the Th2 cell and down-regulation of the Th1 cell, may be associated
      with diseases as diverse as AIDS and asthma. We report herein that by using the
      polymerase chain reaction to analyze the kinetics of in vivo cytokine- and virus
      specific gene expression, we can show that mice infected with the molecularly
      cloned MAIDS defective virus 1/27/A BM5 exhibit an alteration in cytokine gene
      expression that closely parallels an increase in spleen cell numbers, an increase
      in IgM production, a decrease in the stimulation index, and an increase in
      defective-virus gene expression in these mice. As has been suggested to be true
      for human AIDS, the observed alteration of cytokine gene expression suggests that
      a pattern of expression similar to that produced by Th2 cells may also have a
      role in the development of MAIDS.

PMID- 8263748
TI  - High rate of HIV isolation from plasma of asymptomatic patients through
      polyethylene glycol (PEG) treatment.
AB  - The usefulness of traditional methods of HIV plasma titration has been limited by
      poor detection capacity in the asymptomatic phase of HIV disease. We analyzed
      plasma samples from asymptomatic seropositive or early symptomatic patients,
      comparing the classic plasma culture method with the following techniques:
      phorbol 12-myristate 13-acetate treatment of target cells, centrifugal
      inoculation of the virus, heat treatment of cultures, addition of
      monocyte/macrophages to cultures, and polyethylene glycol (PEG) treatment of the
      plasma. Only PEG treatment significantly increased the percentage of HIV
      isolation. The increase of HIV isolation after PEG treatment is more evident in
      patients with higher CD4+ cell counts and those without detectable levels of p24
      antigen. In the p24-negative samples, HIV was isolated in 17 of 24 (71%) with PEG
      treatment versus nine of 24 (37%) with the classic method (p < 0.01). A number of
      discordant samples were found using the classic and PEG methods. Combining the
      positive results obtained with either technique, we obtained an overall HIV
      detection rate of 76%. The increased sensitivity of the combination of PEG and
      classic methods may allow a wider use of plasma viremia as part of the
      virological evaluation of anti-HIV drug efficacy in asymptomatic patients.

PMID- 8263749
TI  - HIV-1 strain dependence of complement-mediated virolysis induced by recombinant
      CD4-IgG.

PMID- 8263750
TI  - Selective inhibition of human immunodeficiency virus type 1 replication by novel
      fluoroalkylated oligomers in vitro.
AB  - Several fluoroalkylated oligomers were found to be potent and selective
      inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Among the
      test compounds, bis(perfluoro-1,4,7,10-tetramethyl-2,5,8,11-tetraoxatetradecyl+
      ++)methacrylic acid oligomer (MAA-HFPO5) emerged as the most potent inhibitor of
      HIV-1 replication. Its 50% antivirally effective concentration for the IIIB
      strain was 2.8 mu g/ml, whereas the compound did not affect the growth and
      viability of mock-infected MT-4 cells at concentrations < or = 100 micrograms/ml.
      MAA-HFPO5 was also inhibitory to other strains of HIV-1 in various human T-cell
      systems, including peripheral blood lymphocytes. MAA-HFPO5 inhibited syncytium
      formation and virus adsorption. The combination of MAA-HFPO5 with either 3'-azido
      3'dioxythymidine or dextran sulfate resulted in an additive effect. Thus,
      fluoroalkylated oligomers are novel HIV-1 inhibitors that warrant further
      evaluation of their therapeutic potential.

PMID- 8263751
TI  - Shortcomings of chest radiography in detecting Pneumocystis carinii pneumonia.
AB  - The radiographic presentation of Pneumocystis carinii pneumonia (PCP) was studied
      in 93 consecutive patients to determine the frequency of normal findings on chest
      roentgenograms and possible correlations with clinical or laboratory findings.
      The roentgenograms were reviewed by two radiologists in an independent, blinded
      way and judged with a score distinguishing between none, interstitial, and acinar
      infiltrates. Discordance mainly between absent versus interstitial and
      interstitial versus acinar infiltrates occurred in 23% of roentgenograms and was
      settled by consensus. The majority of patients presented with moderate-to-mild
      symptoms; the combination of dyspnea, cough, and fever was present in 53%.
      Lactate dehydrogenase (LDH) was elevated in 63%, hypoxemia (PaO2 < 75 mm Hg) was
      present in 57%. Findings on chest roentgenograms were normal in 39%, whereas 36%
      showed interstitial and 25% acinar infiltrates. These three radiographic groups
      represented an increasingly severe PCP, indicated by higher LDH levels and
      hypoxemia (both p < 0.05). In a multivariate logistic regression, normal
      roentgenograms were predicted by low LDH and low peripheral blood granulocytes (p
      < 0.005). Mortality within 3 weeks was only 4% and correlated with the severity
      of infiltrates (p < 0.05). Normal roentgenograms thus corresponded to an
      oligosymptomatic, less severe PCP. In immunodeficient HIV-infected patients, a
      normal chest roentgenogram does not exclude PCP and should not distract from
      attaining a definite diagnosis by examination of induced sputum or
      bronchoalveolar lavage.

PMID- 8263752
TI  - Endocrine function in the HIV wasting syndrome.
AB  - We compared endocrine function in patients with the HIV wasting syndrome with
      other HIV-positive patients without wasting to determine associations between
      endocrine dysfunction and wasting. Sixty-six HIV-seropositive patients were
      evaluated by thyroid, gonadal, and adrenal function tests. Fourteen of these
      patients met the clinical definition of wasting. Total and free testosterone
      levels were significantly lower in patients with wasting compared with patients
      without wasting with both similar and higher mean CD4 counts. Prolactin levels
      were significantly higher, and cortisol levels were higher with borderline
      significance in patients with wasting compared with patients with similar CD4
      counts without wasting. These findings suggest that endocrine function in the HIV
      wasting syndrome differs from that of HIV-infected patients without wasting,
      which may have implications about the pathogenesis and treatment of the HIV
      wasting syndrome.

PMID- 8263753
TI  - Evaluation of recalcitrant pain in HIV-infected hospitalized patients.
AB  - Chronic refractory severe pain in HIV-infected patients is a common and often
      neglected problem. Little data exist evaluating its epidemiology, clinical
      features, and treatment. Our study assessed all HIV-infected inpatients referred
      to the pain control service over a 2-year span. All (24) inpatients with HIV
      infection with chronic refractory severe pain referred to the pain control
      service (PCS) over a 2-year period were prospectively followed daily by trained
      specialists who graded the pain, recommended appropriate therapy, and assessed
      outcome. Ten surviving patients had further long-term outpatient follow-up. The
      patients included 14 intravenous drug abusers, five of whom were on methadone
      maintenance. Localized lower-extremity pain was present in 58%. Pain had been
      present for > or = 1 month in 21 (88%) and for > or = 6 months in 12 (50%). No
      patient had been on pain control around the clock. After PCS consultation, all
      surviving patients (21 of 21, 100%) had partial or total pain relief within 2
      weeks (eight within 1 week) using around-the-clock opioid analgesia adjusted
      daily as necessary. No differences were seen between substance abusing/methadone
      patients and others. No significant adverse reactions or new addiction problems
      were found. Our conclusion is that effective pain control can be achieved using
      around-the-clock opioid analgesia in terminal HIV-infected patients with severe,
      chronic, refractory pain, even if the patients are substance abusers.

PMID- 8263754
TI  - Altered cortisol response and hippocampal atrophy in pediatric HIV disease.
AB  - The hippocampus is a major center for the regulation of the hypothalamic
      pituitary-adrenal axis. There is experimental evidence that chronic exposure to
      high levels of glucocorticoids may be toxic to the hippocampus. We observed
      elevated mean basal and 60-min cortisol (F) levels in response to
      adrenocorticotropin stimulation (0.25 mg cortrosyn, i.v. bolus infusion) in 15
      children with HIV infection. Furthermore, in eight of the children for whom data
      was available, in addition to high peripheral cortisol levels, neurologic
      dysfunction and hippocampal atrophy were noted on CT scan. These preliminary data
      suggest that in HIV-infected children an altered cortisol secretion may be
      associated with specific central nervous system damage.

PMID- 8263755
TI  - Lack of association between anti-V3 loop antibody and perinatal HIV-1
      transmission in Kinshasa, Zaire, despite use of assays based on local HIV-1
      strains.
AB  - Maternal antibodies against the V3 loop principal neutralizing domain (PND) have
      been reported to protect against perinatal HIV-1 transmission. To study this
      association in an African city with a long-standing HIV epidemic and no
      established "consensus sequence" for the V3 loop region of gp120, we determined
      the DNA sequence for the V3 region of HIV-1 from 13 HIV-1-infected residents of
      Kinshasa, Zaire, and developed peptide enzyme immunoassays (EIAs) reflecting the
      V3 loop PND for those HIV-1 strains. Using the most broadly reactive locally
      derived V3 loop peptide in a limited-antigen EIA, there was no significant
      difference in the perinatal HIV-1 transmission risk between 64 women with anti-V3
      loop antibody (transmission risk, 30%) and 104 women without anti-V3 loop
      antibody (transmission risk, 25%; p = 0.5); this finding was unchanged after we
      controlled for maternal AIDS and low birth weight. Although we used assays for V3
      loop antibody based on local HIV-1 strains and evaluated a large number of mother
      child pairs, we found no evidence that maternal anti-V3 loop PND antibody
      protects against perinatal HIV-1 transmission.

PMID- 8263756
TI  - Backcalculation of the number infected with human immunodeficiency virus in
      Germany.
AB  - The method of backcalculation was used to estimate the cumulative number of human
      immunodeficiency virus type 1 (HIV-1)-infected adults in Germany from reporting
      delay-corrected surveillance data on acquired immunodeficiency syndrome (AIDS) in
      the pretreatment era. Using different backcalculation approaches with various
      incubation period distributions, a plausible range of 13,100 to 23,900 HIV-1
      infected adults as of December 31, 1984, was calculated. Estimates of the number
      infected at more recent times were subject to much greater uncertainty. On
      average, the cumulative incidences calculated by the nonparametric backprojection
      method are about 15% lower than the results from the step function model.
      Nonparametric backprojection with the Hessol incubation distribution suggests a
      declining HIV infection rate after 1985, as might be expected from German health
      policies. This distribution is derived from cohorts of homosexual men, the main
      fraction of German AIDS cases.

PMID- 8263757
TI  - Changes in employment, insurance, and income in relation to HIV status and
      disease progression. The Multicenter AIDS Cohort Study.
AB  - While patterns of health care financing for HIV have received considerable
      attention in the literature, the financial impact of disease on individuals
      living with HIV infection has been underexplored, particularly in relation to
      disease progression. Therefore, we sought to document changes in employment,
      income, and insurance coverage over time among HIV-negative, HIV-positive, and
      AIDS-diagnosed gay and bisexual men participating in the Multicenter AIDS Cohort
      Study (MACS) and to document measures of financial hardship. Persons with AIDS
      (PWAs) were 2.7 times more likely to lose full-time employment over a 6-month
      period than seronegative persons (p < 0.05), and loss of employment was strongly
      associated (p < 0.001) with both loss of private health insurance and loss of
      income. Twenty-seven percent of PWAs reported having financial difficulty meeting
      their basic expenses, compared with 10% of seronegative (p < 0.001), and 15% of
      PWAs, compared with only 9% of seronegative persons, said that, for financial
      reasons, they had not sought medical care that they thought they needed (p =
      0.028). When 27% of PWAs in a cohort such as this report financial difficulty
      meeting their basic expenses, it is clear that the response of our public health
      and social welfare systems has not been adequate. Given that the problems
      experienced by most persons infected by HIV are considerably more severe than
      those experienced by MACS participants, the imperative for action is even
      greater.

PMID- 8263758
TI  - Changes in hematologic parameters among Japanese HTLV-I carriers.
AB  - Hematologic data from 1,039 persons who participated in the Miyazaki Cohort study
      on human T-cell lymphotropic virus type-I (HTLV-I) infection were analyzed.
      Individuals were classified by HTLV-I antibody status and the presence of
      abnormal lymphocytes (Ably). We identified several differences in selected
      leukocyte populations: lymphocyte percent was higher among the HTLV-I carriers
      with Ably (36.5 +/- 2.0%, n = 29) compared with the carriers without Ably (33.1
      +/- 0.6%, n = 299) and the seronegatives 36.4 +/- 0.4%, n = 711) (p = 0.04).
      Conversely, there was a trend of decreasing eosinophil percent among both carrier
      groups with the lowest percent among carriers with Ably (1.8 +/- 0.5%) compared
      with the seronegatives (2.8 +/- 0.1%) (p = 0.05). Mean basophil percent was
      decreased among both carriers groups (p = 0.09). Additionally, red cell count was
      elevated among the carriers with Ably (461 +/- 7 x 10(4)/mm3) compared with the
      seronegatives (446 +/- 2 x 10(4)/mm3) (p = 0.03). The HTLV-I carriers with Ably
      had lower serum albumin (4.39 +/- 0.05 g%) compared with the seronegatives (4.47
      +/- 0.01 g%) (p = 0.10). These alterations may be a consequence of HTLV-I
      infection, with the greatest changes among carriers with Ably, a subset thought
      to be at risk for developing adult T-cell leukemia.

PMID- 8263759
TI  - The use of the term "thrush".

PMID- 8263760
TI  - HIV-1 and HBV infection in street youth lodged in security institutes of Buenos
      Aires.

PMID- 8263761
TI  - Endothelin inhibits vasopressin action in rat inner medullary collecting duct via
      the ETB receptor.
AB  - We characterized the endothelin (ET) receptor subtype responsible for the
      inhibition of vasopressin (AVP)-induced increases in osmotic water permeability
      (Pf) and cAMP accumulation in rat inner medullary collecting ducts (IMCD). ET-1
      (10 nM) produced a rapid and transient decrease in AVP-stimulated Pf from 1241 +/
      112 to 224 +/- 38 microns/sec. At the same concentration (10 nM), the selective
      ETB receptor agonist sarafotoxin 6c (S6c) produced the same degree of inhibition
      with a time course identical to that of ET-1. Exposure of IMCDs to the ETA
      selective antagonist BQ123 (100 nM) had no effect on ET-1-induced inhibition of
      AVP-dependent Pf. In suspensions of IMCD cells, ET-1, ET-3 or S6c produced
      concentration-dependent inhibition of AVP-stimulated cAMP accumulation to the
      same extent and with similar potencies (IC50 = 10-30 nM). BQ123 (1 nM to 10
      microM) had no effect on ET-1-induced inhibition of AVP-stimulated cAMP
      formation. Saturation binding experiments with radiolabeled ET-1 and the
      selective ETB agonist IRL1620 and competition binding studies with selective ETA
      and ETB receptor ligands demonstrated that > or = 80% of the ET-1 binding sites
      in IMCD membranes were of the ETB subtype. Therefore, results from functional,
      biochemical and binding studies suggest that the ETB receptor is the ET receptor
      subtype that inhibits AVP action in the rat IMCD.

PMID- 8263762
TI  - Multiple-dose lorazepam kinetics: shuttling of lorazepam glucuronide between the
      circulation and the gut during day- and night-time dosing intervals in response
      to feeding.
AB  - Lorazepam kinetics were examined in seven healthy males age 18 to 30 years after
      single- and multiple-dose lorazepam administration and in the presence and
      absence of neomycin and cholestyramine to block the enterohepatic circulation of
      the drug. Methods used a simultaneous i.v./p.o. dosing regimen with provision to
      measure lorazepam clearance during day- and night-time dosing intervals. The day
      time steady-state clearance of free lorazepam measured 7.55 +/- 1.95 ml/min/kg
      (mean +/- S.D.) and was identical to that observed after single-dose
      administration (7.68 +/- 3.19 ml/min/kg). Neomycin and cholestyramine increased
      lorazepam clearances 5 to 45% (P < or = .05) as would be expected for
      interruption of an enterohepatic circulation and in keeping with previous
      observations under nonsteady-state conditions. Lorazepam clearances were the same
      during the day as during the night, except in the presence of neomycin and
      cholestyramine, where night-time clearances were significantly greater (10.16 +/-
      3.52 vs. 8.77 +/- 2.43 ml/min/kg, P < or = .05). Urinary recoveries of lorazepam
      glucuronide, on the other hand, were greater during the day than during the night
      (114 +/- 11 vs. 77 +/- 15%, P < or = .05) and in all cases were greater than 100%
      of the administered dose for that interval. Thus, there is a diurnal variation in
      lorazepam elimination consistent with a fasting-induced increase in hepatic
      glucuronidation during the night. This, combined with the relative inactivity of
      the gut during this period, serves to trap the glucuronide and delay its transfer
      back to the systemic circulation and urine.

PMID- 8263763
TI  - Cimetidine uptake and interactions with cationic drugs in freshly isolated
      proximal tubular cells of the rat.
AB  - The uptake of cimetidine was investigated in freshly isolated proximal tubular
      cells of the rat as well as its interaction with other cationic drugs. The time
      dependent uptake of 5 microM cimetidine was linear for 2 min and reached
      equilibrium after 10 min. The uptake was reduced at 4 degrees C or by addition of
      5 mM mepiperphenidol. At pH 7.4, only a small percentage (20%) of cimetidine is
      present in the cationic form, which is thought to be necessary for transport by
      the organic cation transporter. At a more acidic pH 6.5, this percentage is
      increased to 67%, but there was no influence on the cellular uptake in comparison
      with control. The cationic form of cimetidine does not seem to be a prerequisite
      for the organic cation transporter in these cells. The uptake of cimetidine was
      concentration-dependent and saturable. The mepiperphenidol-sensitive uptake had a
      high (H) and low (L) affinity apparent Km,H of 6.7 +/- 1.2 microM and Km,L of
      0.61 +/- 0.16 mM, and Vmax,H of 35.8 +/- 2.2 pmol/mg of protein.min and Vmax,L of
      4.5 +/- 0.3 nmol/mg of protein.min. The concentration-dependent inhibition of
      other cationic drugs on 1 microM cimetidine uptake was investigated. The log
      concentration-inhibition curves of mepiperphenidol, famotidine and trimethoprim
      showed a high and low affinity IC50 value, with a potency ranking of
      mepiperphenidol = famotidine > trimethoprim. The other compounds had only a low
      affinity IC50 value and the inhibitory potency ranking was as follows: ranitidine
      = nizatidine > tetraethylammonium > probenecid.

PMID- 8263764
TI  - Effects of extracellular magnesium manipulation on reperfusion-induced
      arrhythmias and myocardial ion shifts in isolated ischemic reperfused rat hearts.
AB  - Isolated rat hearts were subjected to global ischemia followed by reperfusion,
      and a reduction in the incidence of reperfusion-induced ventricular fibrillation
      and ventricular tachycardia was brought about by increasing the extracellular Mg
      concentration in the perfusion buffer. Thus the incidence of ventricular
      fibrillation was reduced from its control value of 100% in 1.2 mM Mg to 83% by
      2.4 mM Mg (P = N.S.), to 42% by 3.6 mM Mg (P < .05), to 17% by 4.8 mM Mg (P <
      .001) and to 17% by 9.6 mM Mg (P < .001). The corresponding values for
      ventricular tachycardia were 100% (control, 1.2 mM Mg) vs. 92% (P = N.S.), 50% (P
      < .05), 25% (P < .01) and 25% (P < .01), respectively. In further studies,
      extracellular Ca was reduced by 50% (1.2 mM) in the perfusion buffer just before
      ischemia and during reperfusion. The incidence of ventricular fibrillation was
      reduced from its control value of 83% in 1.2 mM Mg to 75% by 1.8 mM Mg (P =
      N.S.), to 33% by 2.4 mM Mg (P < .05), to 17% by 3.6 mM Mg (P < .01) and to 8% by
      4.8 mM Mg (P < .01). The incidence of ventricular tachycardia followed the same
      pattern. Myocardial Na, K, Ca and Mg were measured by atomic absorption
      spectrophotometer after the removal of ions from the extracellular space. In
      controls, 30 min of ischemia resulted in 3- and 4-fold accumulation of myocardial
      Na and Ca, respectively, and during reperfusion these values were similar to the
      values for 30-min ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263765
TI  - Quantification of effect delay and acute tolerance development to morphine in the
      rat.
AB  - In this study the effect delay and the development of acute tolerance to
      morphine's antinociceptive effect were investigated in the rat. The
      antinociceptive response induced after three different short infusions of
      morphine was measured by using the electrical stimulation vocalization method.
      Three treatment groups received morphine hydrochloride over 10, 60 and 180 min,
      targeting maximal plasma concentrations of 25 microM at the end of the infusion.
      The maximal concentrations of morphine obtained for the three groups were 29.4 +/
      3.7, 26.7 +/- 4.7 and 28.9 +/- 7.3 microM, respectively. Both an effect delay
      and acute tolerance were observed. For each group, the peak effects were 248 +/-
      82, 337 +/- 116 and 303 +/- 49% above base line, at 35, 65 and 90 min after the
      start of the infusions. A pharmacokinetic-pharmacodynamic model with separate
      effect and tolerance compartments (the ET-model) well described the
      antinociceptive response over time. The antinociceptive effect was best described
      by using a linear model, whereas acute tolerance was best described by using an
      Emax model. The rates of drug equilibration between the plasma and the effect
      compartment (ke0) and the plasma and the tolerance compartment (kt0), expressed
      as half-lives, were 34 +/- 2 and 48 +/- 4 min, respectively. High concentrations
      were required for the acute tolerance to develop (TC50 of 17 microM).

PMID- 8263767
TI  - Attenuation of proarrhythmias related to delayed repolarization by low-dose
      lidocaine in the anesthetized rabbit.
AB  - Polymorphous ventricular tachyarrhythmias (torsades de pointes) were induced in
      seven of eight (88%) anesthetized rabbits receiving the class III antiarrhythmic
      agent almokalant (25 nmol/kg/min i.v.). The tachyarrhythmia was preceded by a
      significant lengthening of the QT interval from 118 +/- 7.2 to 148 +/- 9.0 msec,
      P < .01. Two separate groups of eight rabbits in each were given lidocaine (4.3
      mumol/kg + 12.8 mumol/kg/hr or 12.8 mumol/kg + 38.4 mumol/kg/hr), before
      almokalant was administered. In comparison with the vehicle-pretreated rabbits,
      lidocaine treatment caused a dose-dependent attenuation in the incidence of
      torsades de pointes. Hence, the incidence was reduced to four of eight (50%, P =
      .1538 vs. the vehicle-treated group) rabbits and to none of eight (0%; P = .0007)
      rabbits in the groups treated with the "low" and the "high" dose of lidocaine,
      respectively. This attenuation was observed despite a significant prolongation of
      the QT interval by almokalant (from 128 +/- 7.6 to 175 +/- 15.9 msec, P < .01,
      and from 116 +/- 8.4 to 159 +/- 10.3 msec, P < .001, respectively). Acute
      injection of lidocaine (12.8 mumol/kg, n = 4) during recurrent episodes of
      torsades de pointes in vehicle-treated rabbits caused an abrupt restoration of
      sinus rhythm without influencing the almokalant-induced prolongation of the QT
      interval. It is concluded that lidocaine may inhibit the initiation of and
      suppress rhythm abnormalities related to delayed repolarization.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8263766
TI  - Effect of valproic acid on glycine conjugation of benzoic acid.
AB  - Conjugation with glycine proceeds through ATP-dependent coupling of carboxylic
      acids with coenzyme A (CoA). Therefore, chemicals that form CoA esters may
      interfere with glycine conjugation. We tested the hypothesis that valproic acid
      (VPA), which is esterified with CoA in the first step of its mitochondrial beta
      oxidation, may compromise glycine conjugation of aromatic carboxylic acids, by
      investigating the effect of acute VPA administration on glycine conjugation of
      benzoic acid in rats. VPA administered 1 hr before injection of benzoate only
      decreased the blood clearance of benzoate and the urinary excretion of
      benzoylglycine slightly in normal rats. However, in rats loaded with glycine, 2
      and 3 mmol/kg of VPA reduced the blood clearance of benzoate by 34 and 59%,
      diminished the peak blood level of the glycine conjugate and depressed the
      maximal urinary excretion rate of benzoylglycine by 28 and 66%, respectively. To
      elucidate the mechanism of VPA-induced inhibition of benzoylglycine formation,
      the effects of VPA on hepatic levels of cosubstrates and the activities of
      enzymes involved in glycine conjugation were also determined. One hour after
      administration of VPA, hepatic ATP levels remained unchanged, whereas the
      concentration of CoA was reduced by 67 to 73% and that of glycine was increased
      by 58 to 67%. Activities of the enzymes of glycine conjugation were not
      influenced by VPA. However, 2-n-propyl-4-pentenoic acid, a metabolite of VPA,
      inhibited benzoyl-CoA synthetase. In summary, VPA minimally influenced the
      capacity of glycine conjugation of benzoic acid in normal rats, but decreased it
      markedly in glycine-loaded rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263768
TI  - Stereoselective blockade of amphibian epithelial sodium channels by amiloride
      analogs.
AB  - The blockade of amphibian epithelial sodium channels by amiloride has been shown
      to not be a simple diffusion-limited encounter but rather a selective binding
      process with the rate of approach of the molecule for the channel site determined
      by the side chain at position 2 of the pyrazine ring and the stability of the
      blocking complex provided largely by the bond of the ligand at position 6. The
      presence of such a putative channel-associated receptor suggests that the sodium
      channel might have chiral recognition for its blockers. Using the short-circuit
      technique to measure the amiloride-sensitive sodium current through the apical
      membrane of the toad urinary bladder and frog skins, we evaluated the sodium
      channel-blocking potency of three enantiomeric pairs of amiloride analogs with
      chiral centers on the side chain. We demonstrated the stereoselectivity in sodium
      channel blockade of those analogs and confirmed the existence of a second
      attachment site on the channel for interacting with the lipophilic ligand on the
      side chain of the analog molecule to enhance its blocking activity. Depending on
      the separation between the chiral carbon and the pyrazine ring and the chemical
      groups on the chiral carbon, the eudismic ratio for the 50% inhibition constant
      of the enantiomers, i.e., the ratio of the sodium channel-blocking potency of the
      more active enantiomer to that of the less active enantiomer, was found to range
      from slightly more than 1 to more than 100.

PMID- 8263769
TI  - Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      at the blood-brain barrier.
AB  - The transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors through the blood-brain barrier was studied in vitro by
      using primary cultures of bovine brain capillary endothelial cells (BCEC). The
      uptake of HMG-CoA reductase inhibitors with the lactone form, [14C]lovastatin and
      [14C]simvastatin, was slightly decreased to 65% of the control uptake (37 degrees
      C) at low temperature (4 degrees C) and was not affected by pretreatment of the
      BCEC with metabolic inhibitors (2,4-dinitrophenol and rotenone). [14C]Simvastatin
      acid (the lactone ring-opened form) was taken up in a markedly temperature- and
      concentration-dependent fashion, whereas the uptake of [14C] pravastatin was
      negligible. At pH below 7.4, the uptake rate of [14C]simvastatin acid by the BCEC
      increased markedly with decreasing medium pH, whereas almost pH-independent
      uptake was observed in the presence of 1 mM simvastatin acid. Additional studies
      using an in situ rat brain perfusion method showed that the in vivo
      cerebrovascular permeation of [14C]simvastatin acid in rats was significantly
      inhibited in the presence of 1 mM simvastatin acid, demonstrating that the
      transport system for the acid forms of HMG-CoA reductase inhibitors functions
      under in vivo conditions. Several monocarboxylic acids significantly inhibited
      the uptake of [14C]simvastatin acid by the BCEC, whereas dicarboxylic acids did
      not. The uptake of [14C]simvastatin acid by the BCEC was competitively inhibited
      by 15 mM acetic acid. Accordingly, we concluded that HMG-CoA reductase inhibitors
      in lactone form are transported via simple diffusion, whereas those having an
      acid form are transported across the blood-brain barrier via a carrier-mediated
      transport mechanism for monocarboxylic acids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263770
TI  - Vascular pharmacodynamics of NG-nitro-L-arginine methyl ester in vitro and in
      vivo.
AB  - The inhibitory effects of NG-nitro-L-arginine methyl ester (L-NAME) on
      endothelium-dependent vasodilatation were studied in conscious rats and isolated
      rat aortic rings. In phenylephrine (PE, ED90)-preconstricted aortae, L-NAME
      caused prolonged and complete inhibition of acetylcholine (ACh)-induced
      relaxation with IC50 of 4 x 10(-7) M and Hill coefficient (n) of 1. The
      inhibition was abolished by L-arginine (L-Arg), independently of whether it was
      applied 10 min earlier or 4 hr later than L-NAME. Intravenous bolus injection of
      L-NAME caused prolonged increases in mean arterial pressure (MAP), with Emax of
      50 +/- 7 mm Hg, ED50 of 5 +/- 1 x 10(-6) mol/kg and n of 2. Intravenous infusion
      of L-Arg shifted the dose-MAP curve of L-NAME to the right without changing Emax
      or n. A modified Schild plot (n = 2) for the action of L-NAME gave a slope not
      different from unity, suggesting that L-Arg inhibits competitively the MAP
      response of L-NAME. Intravenous infusion of ACh decreased MAP in rats treated
      with L-NAME (4.8 x 10(-5) mol/kg) or PE. Compared to PE-treated rats, L-NAME
      inhibited the depressor response to ACh by 50%. Thus, a dose of L-NAME 10 times
      its ED50 in raising MAP only partially blocked the depressor responses to
      ACh.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263771
TI  - The P1-purinoceptors that mediate the prejunctional inhibitory effect of
      adenosine on capsaicin-sensitive nonadrenergic noncholinergic neurotransmission
      in the rat mesenteric arterial bed are of the A1 subtype.
AB  - It has been shown that capsaicin-sensitive sensory-motor nerves contribute to the
      control of peripheral vascular resistance by releasing the potent vasodilator
      calcitonin gene-related peptide. The purpose of the present study was to
      characterize the P1-purinoceptor subtype that modulates capsaicin-sensitive non
      adrenergic noncholinergic (NANC) neurotransmission in the rat mesenteric arterial
      bed. Analogs of adenosine, selective for the adenosine receptor subtypes A1 or
      A2, were evaluated on the vasodilator response to electrical stimulation of
      capsaicin-sensitive sensory-motor nerves. The order of potency of adenosine
      receptor agonists to inhibit the NANC neurotransmission was: the selective
      adenosine A1 receptor agonist N6cyclopentyl-adenosine > or = R
      phenylisopropyladenosine > 5'N-ethylcarboxamide adenosine > or = 2
      chloroadenosine > or = S-phenylisopropyladenosine. The A2-selective agonist CGS
      21680 was devoid of any effect on NANC neurotransmission. In addition, the
      selective A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine inhibited
      the effect of adenosine. None of the agonists tested showed direct action on the
      tone of the mesenteric vasculature. Neither N6cyclopentyladenosine nor adenosine
      modified the vasodilator response to exogenous calcitonin gene-related peptide.
      Moreover, adenosine failed to affect the vasodilator response to capsaicin. In
      conclusion, these results indicate that adenosine and its analogs inhibit NANC
      neurotransmission via prejunctional P1-purinoceptors of the A1 subtype. The
      inhibitory action of adenosine appears to be selective for the release of
      transmitters during electrical activation of sensory-motor nerve endings,
      adenosine being inactive on capsaicin-induced vasodilatation.

PMID- 8263772
TI  - Dopaminergic functional supersensitivity: effects of chronic L-dopa and carbidopa
      treatment in an animal model of Parkinson's disease.
AB  - We have evaluated the effects of L-Dopa and carbidopa treatment (30 days) on
      dopamine (DA) turnover, intracellular cyclic AMP (cAMP) accumulation and
      tetrahydrobiopterin levels in the nigrostriatal pathway of rats with a unilateral
      6-OHDA lesions (greater than 90% lesions). We observed significant increase in
      the 3,4-dihydroxy-phenylacetic acid/DA and homovanillic acid/DA ratios, and in
      basal cAMP levels (92%) in the ipsilateral striatum, but not in the substantia
      nigra when compared to the contralateral intact hemisphere. After L
      dopa/carbidopa treatment, the increased 3,4-dihydroxy-phenylacetic acid/DA,
      homovanillic acid/DA ratios and the elevated levels of cAMP in the ipsilateral
      striatum were reduced significantly and returned to the control levels of
      contralateral non-lesioned side. Tetrahydrobiopterin levels obtained on both
      sides remained unaffected after treatment. The D1 agonist SKF 38393 (10 microM)
      increased cAMP accumulation significantly in striatal slices from the lesioned
      and intact hemispheres in both vehicle and treatment group, which were completely
      inhibited by the D1 antagonist SCH 23390 (10 microM). In contrast, the ability of
      SKF 38393 to enhance the cAMP accumulation was blocked by the D2 agonist
      quinpirole (10 microM) in striatal slices from the intact hemisphere, but not
      from the lesioned side. In substantia nigra, no significant differences in cAMP
      accumulation were observed. Our data suggests that chronic L-dopa/carbidopa
      treatment reverses the increased dopaminergic activity and D1 receptor functional
      supersensitivity seen after 6-hydroxydopamine lesions, and indicates a D1
      receptor-mediated action of L-dopa.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263773
TI  - Tyrphostin attenuates platelet-derived growth factor-induced contraction in
      aortic smooth muscle through inhibition of protein tyrosine kinase(s).
AB  - The effect of protein tyrosine kinase (PTK) inhibition on spontaneously
      hypertensive rat vascular smooth muscle contraction was examined in this study.
      By using isolated aortic strips, it was found that platelet-derived growth factor
      (PDGF) (0.1-1 nM), an activator of PTKs, elicited contraction with an EC50 of
      0.25 +/- 0.08 nM. Treatment with tyrphostin (0.02-200 microM), a selective
      inhibitor of PTKs, caused a significant rightward shift of the concentration
      response curves (P < .05). The IC50 for tyrphostin in the spontaneously
      hypertensive rat was calculated to be 9.5 +/- 4.2 microM. Tyrphostin also
      inhibited contractile activity in normotensive control Wistar-Kyoto rat aorta
      with an IC50 of 0.24 +/- 0.09 microM. Tyrphostin inhibited PDGF-induced
      contraction over a range of calcium concentrations, suggesting that it may oppose
      contraction through inhibition of calcium influx via PDGF-induced receptor
      operated channel. However, KCl-mediated voltage-operated calcium channels were
      largely unaffected by tyrphostin, because it was unable to relax aortae which had
      been partially depolarized. Tyrphostin also had no significant antagonistic
      effect on contraction induced by phenylephrine or phorbol-12,13-dibutyrate. For
      both of these agents, contraction is mediated through activation of protein
      kinase C, which further alludes to the specificity of tyrphostin for PTKs.
      Treatment with 1 nM PDGF caused a significant stimulation of particulate/membrane
      PTK activity in the aorta. Tyrphostin attenuated PDGF-induced PTK activity in a
      concentration-dependent manner. The data suggest that PTKs may play a role in
      vascular smooth muscle contraction and that specific inhibition of PTK activity
      results in vasorelaxation. Furthermore, the results suggest that vasoconstriction
      and vascular smooth muscle cell proliferation may share common biochemical
      signalling pathways.

PMID- 8263774
TI  - Identification of a P2Y-purinergic receptor that inhibits adenylyl cyclase.
AB  - Adenine nucleotides inhibited isoproterenol- and forskolin-stimulated cyclic AMP
      accumulation in C6-2B rat glioma cells. Inhibition occurred in the presence of a
      phosphodiesterase inhibitor, and no effect of adenine nucleotides was observed in
      direct measurements of phosphodiesterase activity in intact cells. Pretreatment
      of C6-2B glioma cells with pertussis toxin blocked the inhibitory effects of P2Y
      purinergic receptor agonists. The pharmacological specificity for a series of ATP
      and ADP analogs (2-methylthioadenosine 5'-triphosphate > or = 2
      methylthioadenosine 5'-diphosphate > adenosine 5'-O-(2-thiodiphosphate) > 2
      chloro-adenosine 5'-triphosphate = ADP = adenosine 5'-O-(3-thiotriphosphate) >
      ATP > UTP) was similar to that expected of a P2Y-purinergic receptor; the P2X
      purinergic receptor agonists, alpha,beta-methyleneadenosine 5'-triphosphate and
      beta,gamma-methylene-adenosine 5'-triphosphate, had no effect. Because activation
      of phospholipase C occurs in response to P2-purinergic receptor activation in
      many target tissues, the effects of P2Y-receptor agonists on inositol phosphate
      accumulation were measured in C6-2B cells. No evidence for P2Y-purinergic
      receptor-mediated regulation of inositol lipid metabolism was observed under
      conditions where muscarinic cholinergic receptor activation or AIF4-markedly
      increased inositol phosphate accumulation. These results suggest that a P2
      purinergic receptor subtype with distinct signaling properties exists on C6-2B
      rat glioma cells. Although this receptor expresses the general pharmacological
      specificity of a phospholipase C-coupled P2Y-purinergic receptor, it may
      represent a unique receptor subtype since it inhibits adenylyl cyclase.

PMID- 8263775
TI  - Effects of isoenzyme-selective inhibitors of cyclic nucleotide phosphodiesterase
      on microvascular leak in guinea pig airways in vivo.
AB  - The effects of drugs elevating cyclic nucleotide concentrations or inhibiting
      cyclic nucleotide phosphodiesterase (PDE) activity on platelet activating factor
      (PAF)-induced microvascular leak (MVL) was examined in the anesthetized guinea
      pig. Drugs were dosed as dry powders directly into the tracheobronchial tree and
      MVL was assessed by using the fluorescent macromolecule fluorescein
      isothiocyanate-dextran (FITC-dextran, 150 kD). Basal FITC-dextran content was 15
      +/- 1 and 23 +/- 4 ng.mg-1 of tracheal and bronchial tissue, respectively, and
      0.6 +/- 0.03 micrograms.ml-1 of tracheobronchial lavage fluid. PAF (2-8 nmol,
      intratracheal (i.t.) administration) produced a dose-dependent increase in MVL;
      the maximum increase being 100% in tracheal and bronchial tissue and 400% in
      lavage fluid. PAF (16 nmol) produced acute bronchospasm. The beta-2 adrenoceptor
      agonist salbutamol (50 or 200 micrograms i.t.) and the nitrovasodilator sodium
      nitroprusside (200 or 500 micrograms i.t.), which activate adenylyl and guanylyl
      cyclases, respectively, potently and significantly (P < .05) inhibited PAF
      induced MVL in airway tissues and in the airway lumen by 60 to 100%. Sodium
      nitroprusside (50 micrograms i.t.) only significantly inhibited MVL into the
      lavage fluid. Inhibition of PDE type IV with rolipram (200 micrograms i.t.) or
      PDE type V with zaprinast (200 micrograms i.t.) potently (by 70-100%) and
      significantly (P < .05) reduced MVL into the airways. Lower doses (20 micrograms)
      were without effect. Neither vinpocetine (PDE type I inhibitor) nor siguazodan
      (PDE type III inhibitor) inhibited MVL. Theophylline (200 micrograms i.t.)
      inhibited MVL into lower airway tissues and lavage fluid but was without marked
      effect in tracheal tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263776
TI  - Inhibition of norepinephrine release from rat cortex slices by opioids:
      differences among agonists in sensitivities to antagonists suggest receptor
      heterogeneity.
AB  - Receptors mediating opiate-induced inhibition of potassium-stimulated release of
      [3H]norepinephrine (NE) from slices of rat cortex incubated in vitro have been
      characterized by comparison of the pA2 values of the competitive antagonists,
      naloxone, D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), nor-binaltorphimine,
      naltrindole and bremazocine against the agonists, Tyr-D-Ala-MePhe-Gly-ol (DAMGO),
      Tyr-D-Arg-Phe-Sar (TAPS), [D-Ser2, Leu5]enkephalyl-Thr (DSLET), beta-endorphin
      [beta-END(1-31)] and ethylketocyclazocine (EKC). There were significant
      differences among agonists in their sensitivities to each antagonist. The delta
      receptor selective agonist, DPDPE, and the kappa 1-agonist, U69593, did not
      inhibit NE release, indicating that delta and kappa 1 receptors are not involved.
      DAMGO, TAPS and DSLET generally behaved as mu agonists, although TAPS and DSLET
      were less sensitive to antagonism by CTOP than by DAMGO. TAPS and DSLET showed
      similar sensitivities to all antagonists, suggesting that they acted through
      similar receptors, possibly of the mu 1 type. beta-END(1-31) and EKC differed
      from DAMGO and from each other in their sensitivities to most antagonists. Shifts
      in agonist concentration-response curves induced by prior treatment of the rats
      with the noncompetitive antagonists, beta-funaltrexamine and naloxonazine, also
      suggested that EKC and beta-END(1-31) acted through mechanisms differing from
      those used by DAMGO, TAPS and DSLET. It is possible that EKC and beta-END(1-31)
      acted via kappa 2 and/or epsilon receptors. These results suggest that there is
      heterogeneity in the opioid receptors regulating NE release in rat cortex.

PMID- 8263777
TI  - Migrating motor complex of the intestine and absorption of a biliary excreted
      drug in the dog.
AB  - The role of the migrating motor complex (MMC) of the small intestine in the
      absorption of an enterally administered marker (tolfenamic acid, TA) used to
      investigate enterohepatic recycling was studied in the fasted dog. TA was rapidly
      and extensively absorbed in the duodenum as well as in the ileum. In contrast,
      the conjugated form of TA (CTA) was not absorbed in the duodenum but only in the
      ileum, i.e., after bacterial hydrolysis. By administering CTA in the duodenum at
      different phases (I and II) of the MMC, it was shown that CTA had to be propelled
      from the duodenum to the ileum by the motor activity of the MMC. Under these
      conditions, the peak plasma TA concentration was only observed when phase II of
      the MMC present in the duodenum at the time of CTA administration arrived in the
      ileum. The estimated mean transit time of CTA from the duodenum to ileum was 45
      min and the mean hydrolysis time of CTA to TA was about 75 min. It was concluded
      that 1) in the fasted dog, a relatively long delay must exist between bile
      excretion of a conjugate and the reabsorption of its free moiety in the ileum and
      2) a realistic physiological model of enterohepatic recycling must take into
      account the MMC pattern of the intestine when drugs are administered to animals
      in the fasted state.

PMID- 8263778
TI  - Differential blockade by tachykinin NK1 and NK2 receptor antagonists of
      bronchoconstriction induced by direct-acting agonists and the indirect-acting
      mimetics capsaicin, serotonin and 2-methyl-serotonin in the anesthetized guinea
      pig.
AB  - This study has examined the abilities of (+/-)-CP96345 and (+/-)-SR48968,
      nonpeptide antagonists selective for the tachykinin NK1 and NK2 receptors,
      respectively, to block bronchoconstriction caused by intravenous administration
      of direct-acting receptor agonists and the indirect-acting mimetics capsaicin,
      serotonin and 2-methyl-serotonin in the anesthetized guinea pig. The NK1
      antagonist (+/-)-CP96345 was found to cause, at a maximally tolerated dose of 9
      mumol/kg, an approximate 10-fold rightward shift of the dose-response curves for
      selective NK1 agonists substance P (SP), [Sar9,Met(O2)11]SP and Ac
      [Arg6,Sar9,Met(O2)11]SP6-11 without altering responses to selective NK2 agonists
      neurokinin A (NKA), [Nle10]NKA4-10 or [beta-Ala8]NKA4-10. The NK2 antagonist (+/
      )-SR48968 caused dose-dependent rightward shifts of the dose-response curves for
      the NK2 but not the NK1 agonists. Results using combinations of the receptor
      antagonists indicate that the NK2 agonists could cause bronchoconstriction by
      acting on the NK1 receptors at large doses relative to those used without
      antagonists. Of the agonists used here, [beta-Ala8]NKA4-10 appeared to be the
      most selective for the NK2 receptors. When used alone, only (+/-)-SR48968 was
      found to block bronchoconstriction caused by capsaicin, serotonin (after blockade
      of 5-HT2 receptors by LY53857) and 2-methyl-serotonin. When (+/-)-CP96345 was
      also given, larger additional blockade was seen with capsaicin than with
      serotonin or 2-methyl-serotonin as mimetic substance. Atropine caused small and
      variable degrees of blockade of serotonin and 2-methyl-serotonin but not of
      capsaicin after combinations of the two antagonists.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263779
TI  - SC-49992, a mimetic of the peptide arginine-glycine-aspartic acid-phenylalanine
      that blocks platelet aggregation, enhances recombinant tissue plasminogen
      activator-induced thrombolysis and prevents reocclusion in a canine model of
      coronary artery thrombosis.
AB  - 8-Guanidino-octanoyl-aspartic acid-phenylalanine (SC-49992), a mimetic of the
      tetrapeptide arginine-glycine-aspartic acid-phenylalanine, is a potent inhibitor
      of platelet aggregation. In this study, the authors examined the effects of SC
      49992 on the time to lysis of thrombi and the time to reocclusion in the canine
      coronary artery, which had been treated with tissue plasminogen activator. A
      lysis/reocclusion model was used that was originally designed so that the
      reoccluding thrombus was platelet rich. SC-49992 decreased the time to lysis in
      response to recombinant tissue plasminogen activator in a dose-dependent manner.
      The reduction of the lytic time was significant at the highest dose of 0.08 mg kg
      1 min-1 (from 22.8 +/- 8.2 to 7.4 +/- 1.4 min, P < .05). The reocclusion time was
      prolonged at all doses of SC-49992 (from a control level of 3.4 +/- 0.6 min to
      more than 50 min at all doses of SC-49992, P < .05). At the 0.06- and 0.08-mg kg
      1 min-1 doses, all but one animal in each group did not have a reocclusion during
      the time of the experiment. In those animals that did have reocclusions in the
      presence of SC-4992, ex vivo platelet aggregation was inhibited 100% at the time
      of reocclusion. The bleeding times were prolonged in these animals at the levels
      of inhibition in which the compound was the most effective.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8263780
TI  - Absence of receptor reserve at hippocampal muscarinic autoreceptors which inhibit
      stimulus-dependent acetylcholine release.
AB  - The extent of reserve among inhibitory muscarinic autoreceptors on hippocampal
      cholinergic nerve terminals was examined in superfused calcium-naive
      synaptosomes. The tissues were treated with the irreversible muscarinic
      cholinergic receptor antagonist propylbenzilycholine mustard (PrBCM) and then
      used to assess the functional status of autoreceptors through acetylcholine (ACh)
      induced inhibition of calcium-evoked [3H]ACh release. PrBCM treatment caused a
      marked reduction in the density of high-affinity [3H]quinuclidinyl benzilate
      binding sites (46%, 72% and 90% reductions after 3, 6 or 10 nM PrBCM,
      respectively) but had no apparent influence on the binding affinities or relative
      proportions of high- and low-affinity binding sites for the M1-selective
      antagonist pirenzepine or the agonist ACh. In vehicle-treated tissues, ACh was a
      potent (EC50 = 240 nM) and efficacious (maximal inhibition of stimulated [3H]ACh
      release = 65%) agonist at muscarinic autoreceptors. However, after PrBCM
      treatment, the maximal inhibition for ACh was greatly attenuated (35% and 17% for
      3 and 6 nM PrBCM, respectively) with no concurrent changes in the EC50 or slope
      factor. Comparisons of equieffective agonist concentrations before and after
      receptor occlusion revealed a direct linear relationship between autoreceptor
      occupancy and inhibition of [3H]ACh release with close agreement between the
      calculated agonist dissociation constant (KA = 220 nM) and the EC50 for ACh.
      Pretreatment with 100 nM atropine methylbromide completely prevented PrBCM
      induced reductions in muscarinic cholinergic receptor binding and autoreceptor
      function. These results support the conclusion that muscarinic autoreceptors on
      hippocampal nerve endings exhibit little or no reserve for inhibition of ACh
      release by the endogenous neurotransmitter.

PMID- 8263781
TI  - Distinct muscarinic receptors, G proteins and phospholipases in esophageal and
      lower esophageal sphincter circular muscle.
AB  - Acetylcholine (ACh)-induced contraction of esophageal circular smooth muscle
      cells was inhibited by the M2 muscarinic antagonist methoctramine. In lower
      esophageal sphincter (LES) cells contraction was inhibited by the M3 antagonist p
      fluoro-hexa-hydro-sila-difenidol (pF-HSD). Pertussis toxin (PTX) reduced ACh
      induced contraction of esophageal but not of LES cells, which suggested that
      different receptor-linked G proteins are involved. Antibodies against G13
      antagonized contraction of esophageal cells and G9-G11 antibodies antagonized
      contraction of LES cells. The phosphatidylinositol-specific phospholipase C (PLC)
      inhibitors, U-73122 and neomycin, reduced ACh-induced contraction of LES but not
      of esophageal cells. Conversely, propranolol and p-chloromercuribenzoic acid
      (pCMB), which inhibit a phosphatidylcholine-specific phospholipase D (PLD)
      dependent pathway, reduced contraction of esophageal but not of LES muscle cells.
      At 1 and 5 sec after the administration of ACh (10(-5) M), inositol 1,4,5
      trisphosphate (IP3) increased only in LES muscle, which suggested that
      contraction results from PLC-induced IP3 production in the LES but not in the
      esophagus. The IP3 receptor antagonist heparin, and depletion of intracellular
      Ca++ stores by thapsigargin or A23187, inhibited ACh-induced contraction of LES
      but not of esophageal muscle. It was concluded that ACh-induced esophageal
      contraction depends preferentially on M2 receptors, a PTX-sensitive G13 protein,
      phosphatidylcholine-specific PLD and production of diacylglycerol (DAG) and is
      independent of IP3 formation and the release of intracellular Ca++. Conversely,
      LES contraction is mediated through M3 receptors, a PTX-insensitive G9-G11
      protein, activation of PLC, IP3 formation and the release of intracellular Ca++.

PMID- 8263782
TI  - Effect of the beta-carboline abecarnil on spinal reflexes in mice and on muscle
      tone in genetically spastic rats: a comparison with diazepam.
AB  - Abecarnil is a beta-carboline agonist at benzodiazepine receptors with potent
      anxiolytic activity but no muscle relaxant side effects in rodents. Clinical
      experience suggests that changes in the muscle tone induced by benzodiazepines
      are related to their effects on spinal reflexes. The authors therefore analyzed
      the effect of treatment with abecarnil on spinal monosynaptic (Hoffmann reflexes)
      and polysynaptic (flexor) reflexes in mice and the influence of abecarnil on
      muscle tone in genetically spastic rats. The i.v. administration of abecarnil in
      mice (dose range, 0.02-1 mg/kg) depressed flexor reflexes in a dose-dependent
      manner; Hoffmann reflexes remained unchanged. Administration of diazepam i.v.
      (0.01-1 mg/kg) also reduced flexor reflexes and had little or no effect on
      Hoffmann reflexes. In genetically spastic rats, i.v. administration of abecarnil
      (10-30 mg/kg) decreased the muscle tone in a dose- and time-dependent manner. A
      similar muscle relaxant effect was observed in such rats after i.v.
      administration of diazepam (0.1-0.8 mg/kg). By contrast, i.p. administration of
      abecarnil in mice did not influence spinal reflexes up to the dose of 1 mg/kg
      and, in genetically spastic rats, did not affect muscle tone up to the dose of
      100 mg/kg. Administration of diazepam i.p. (1 mg/kg) depressed flexor reflexes in
      mice and over the range 0.2 to 5 mg/kg produced a dose- and time-dependent
      decrease of muscle tone in genetically spastic rats. The muscle relaxant effect
      of i.p. diazepam could be antagonized by i.p. administered abecarnil. These
      studies thus demonstrate that i.v. but not i.p. administration of abecarnil may
      result in muscle relaxant action in mice and in genetically spastic rats.

PMID- 8263783
TI  - Determination and metabolism of dithiol chelating agents. XV. The meso-2,3
      dimercaptosuccinic acid-cysteine (1:2) mixed disulfide, a major urinary
      metabolite of DMSA in the human, increases the urinary excretion of lead in the
      rat.
AB  - Meso-2,3-dimercaptosuccinic acid (DMSA) in humans is an effective p.o.
      therapeutically useful chelating agent of Pb. In humans given DMSA p.o., the
      major urinary metabolite is DMSA-cysteine (1:2) mixed disulfide. In order to
      determine its efficacy in mobilizing Pb and increasing urinary Pb excretion, the
      mixed disulfide was given to rats treated previously with Pb acetate. The mixed
      disulfide was as effective as DMSA in increasing the urinary excretion of Pb and
      mobilizing Pb from the kidney. DMSA, however, appears to be superior for
      mobilizing Pb from the liver and the brain. After the mixed disulfide was given
      s.c. to rats, DMSA was found in the blood and urine. Twenty-four hours after
      administration, 0.7% of the administered mixed disulfide was found in the urine
      as DMSA, indicating the mixed disulfide can be reduced to DMSA. The mixed
      disulfide was also reduced in vitro to DMSA during incubation with rat blood.
      Although in the rat the DMSA-cysteine (1:2) mixed disulfide mobilized Pb from the
      kidney, increased the urinary excretion of Pb and was to some extent reduced to
      DMSA, its fate and pharmacological properties in the human, where it is found
      after DMSA administration, are unknown.

PMID- 8263784
TI  - Microdialysis study of zidovudine (AZT) transport in rat brain.
AB  - The concentration profiles of [14C]3'-azido-3'-deoxythymidine (AZT) emanating
      from an acutely implanted microdialysis probe were measured in rat caudate
      putamen by quantitative autoradiography for infusions of 14 min and 1 and 2 h. A
      mathematical model which simulated diffusive solute transport, unaffected by the
      processes of microvascular exchange or tissue metabolism, did not fit the
      observed concentration profiles. Chromatographic analysis of brain homogenates
      for metabolites of AZT showed that the rate of metabolic transformation was not
      large enough to affect transport of the drug through the brain tissue. A model
      simulating the effect of microvascular exchange on the diffusion profiles fit the
      observed concentration profiles and the transient change in the dialysate
      extraction fraction. This analysis yielded an estimated tissue elimination rate
      constant for microvascular exchange of Kel = 0.013 ml/(g.min) and an intra- to
      extracellular partition coefficient of K pi = 1.04. Inclusion of probenecid in
      the dialysate, together with an i.p. injection, led to a substantial increase in
      the diffusion distance of the labeled AZT from the microdialysis probe,
      suggesting at least a 4-fold decrease in the microvascular exchange rate
      constant. These results imply that AZT is actively transported out of the brain
      parenchyma to the microvasculature and that this active transport mechanism is
      responsible for the limited central nervous system penetration of systemically
      administered AZT, in spite of its high lipid solubility.

PMID- 8263785
TI  - Comparison of thrombin active site and exosite inhibitors and heparin in
      experimental models of arterial and venous thrombosis and bleeding.
AB  - Different pharmacological approaches to thrombin inhibition were compared for
      their effects on thrombosis and bleeding time in anesthetized rats. Thrombosis
      was induced in the carotid artery by transmural vessel injury and in the vena
      cava by partial blood flow stasis combined with mild endothelial disruption.
      Small mesenteric arteries were punctured with a hypodermic needle to measure the
      bleeding time. Dose-response relationships were determined with a thrombin active
      site inhibitor, N-methyl (GYKI 14,766); a thrombin exosite inhibitor, succinyl
      Phe-Glu-Pro-Ile-Pro-Glu-Glu-Tyr-cyclohexylalanine-Gln (BMS 180,742); and heparin.
      BMS 180,742 interferes with fibrinogen binding to the thrombin exosite but,
      unlike GYKI 14,766, it does not block thrombin's catalytic site. The effects on
      thrombosis and bleeding time were correlated with ex vivo clotting times using
      the activated partial thromboplastin time for heparin and the thrombin time for
      GYKI 14,766 and BMS 180,742. Venous thrombosis was inhibited more than 90% by all
      three inhibitors at doses that either produced threshold increases or had no
      effect on bleeding and clotting times. Arterial thrombosis was inhibited 82% by
      GYKI 14,766 and 63% by heparin but it was not inhibited by BMS 180,742. These
      antithrombotic activities were accompanied by a maximal activated partial
      thromboplastin time increase and doubling of the bleeding time with heparin and a
      maximal thrombin time prolongation and 35% increase in bleeding time with GYKI
      14,766. These results suggest that thrombin inhibitors, which act at the active
      site or exosite or through antithrombin III, are equally efficacious against
      venous thrombosis but active site inhibitors are the most effective against
      arterial thrombosis.

PMID- 8263786
TI  - An alternative mechanism for the inhibition of cholesterol biosynthesis in HepG2
      cells by N-[(1,5,9)-trimethyldecyl]-4 alpha,10-dimethyl-8-aza-trans-decal-3 beta
      ol (MDL 28,815).
AB  - Compounds that block hepatic cholesterol biosynthesis and secretion may be useful
      hypocholesterolemic agents. N-[(1,5,9)-trimethyldecyl]-4 alpha,10-dimethyl-8-aza
      trans-decal-3 beta-ol (MDL 28,815) has been shown to block cholesterol
      biosynthesis in 3T3 fibroblasts and it causes cellular accumulation of squalene
      2,3-epoxide and squalene 2,3:23,24-diepoxide (squalene epoxides), which suggests
      that it inhibits 2,3-oxidosqualene cyclase. The purpose of the present report was
      to determine whether MDL 28,815 acts only at the level of 2,3-oxidosqualene
      cyclase or whether other enzymes in the cholesterol biosynthetic pathway are
      affected. HepG2 cells, grown in lipoprotein-deficient serum, were incubated with
      MDL 28,815 and 14C-acetate to radiolabel cholesterol and the intermediates in the
      cholesterol biosynthetic pathway. Blockade of cholesterol biosynthesis by MDL
      28,815 in these cells was associated with the accumulation of two metabolites,
      one of which was 5 alpha-cholest-8-en-3 beta-ol. The other metabolite was
      identified by a combination of ultraviolet spectrometry, gas chromatography, mass
      spectroscopy and analytical high-performance liquid chromatography as 5 alpha
      cholest-8,14-dien-3 beta-ol. Maximal blockade of cholesterol biosynthesis was
      associated with the accumulation of these two metabolites and, in particular, 5
      alpha-cholest-8,14-dien-3 beta-ol, rather than with squalene epoxides. These
      results suggest that MDL 28,815 blocks cholesterol biosynthesis primarily by the
      inhibition of sterol-delta 14-reductase, and possibly sterol-delta 8-ene
      isomerase, rather than 2,3-oxidosqualene cyclase.

PMID- 8263787
TI  - The regulation of regional hemodynamics by alpha-1 adrenoceptor subtypes in the
      conscious rat.
AB  - The role of alpha-1 adrenoceptors sensitive and resistant to chloroethylclonidine
      (CEC) in the regulation of peripheral hemodynamics in the conscious rat has been
      examined. CEC treatment (15, 25 or 30 mg/kg i.p.) resulted in a sustained
      decrease in systemic arterial blood pressure and heart rate. These same
      concentrations reduced, but did not eliminate, [3H]prazosin binding sites in
      vascular smooth muscle homogenates. The effect of CEC administration on blood
      flow and regional vascular resistance was assessed using pulsed-Doppler flow
      probes implanted around the superior mesenteric and iliac arteries. CEC treatment
      resulted in a significant decrease in mesenteric and hindlimb resistance.
      Prazosin (3 or 5 mg/kg) reduced systemic arterial blood pressure and vascular
      resistance to a greater degree than did CEC. The dose-response curve for
      phenylephrine-induced increases in mesenteric or hindlimb vascular resistance was
      shifted only 2- to 10-fold to the right by CEC. Prazosin, by contrast, shifted
      the phenylephrine dose-response curve over 100-fold to the right. These data
      indicate that multiple alpha-1 adrenoceptor subtypes, both CEC sensitive and
      insensitive, participate in the regulation of blood flow to the gut and the
      hindlimb. Finally, CEC sensitive sites do not appear to play as prominent a role
      as insensitive sites in mediating the pressor response to phenylephrine.

PMID- 8263788
TI  - Fluoxetine prevents the disruptive effects of fenfluramine on differential
      reinforcement-of-low-rate 72-second schedule performance.
AB  - This study compared the effects of fenfluramine and fluoxetine on the
      differential-reinforcement-of-low-rate 72-s schedule of reinforcement.
      Fluoxetine, a clinically effective antidepressant, increases extracellular
      serotonin (5-HT) by blocking the uptake of 5-HT after release. Fenfluramine
      increases extracellular 5-HT through transporter-mediated release (although it
      also blocks 5-HT uptake). The following characteristics were identified. First,
      fenfluramine and fluoxetine had two different effects on the differential
      reinforcement-of-low-rate 72-s schedule. Fluoxetine had an antidepressant-like
      effect by increasing reinforcement rate without disrupting the interresponse time
      distribution. Fenfluramine's effect on the differential-reinforcement-of-low-rate
      72-s schedule was not antidepressant-like: it did not increase the reinforcement
      rate, whereas it did disrupt the interresponse time distribution. Second, when
      fluoxetine and fenfluramine were given in combination, fluoxetine prevented the
      disruptive effects of fenfluramine. This result is consistent with fluoxetine's
      ability to block fenfluramine-induced 5-HT release, and supports the argument
      that the uptake transporter mediates fenfluramine's effects on both 5-HT release
      and behavior. Putative behavioral mechanisms (waiting capacity and temporal
      discrimination) which may mediate the acute effects of fluoxetine are discussed.

PMID- 8263789
TI  - Activation of voltage-dependent calcium channels in Kupffer cells by chronic
      treatment with alcohol in the rat.
AB  - Calcium is essential for activation of Kupffer cells and it was recently reported
      that Kupffer cells contain L-type voltage-dependent Ca++ channels. The purpose of
      the present study was to evaluate the effect of chronic ethanol treatment on Ca++
      channels. Kupffer cells were isolated from rats fed either a control liquid diet
      or a liquid ethanol-containing diet for 5 to 8 weeks. The cytosolic free calcium
      concentration ([Ca++]i) was measured in freshly isolated Kupffer cells with the
      fluorescent Ca++ indicator, fura-2. In Kupffer cells isolated from the control
      group, partial replacement of extracellular Na+ by K+ caused a concentration
      dependent increase in [Ca++]i (half-maximal effect, 83 +/- 1 mM K+) presumably as
      a result of membrane depolarization. The concentration-response curve for K+ was
      shifted significantly (P < .01) to the left in cells isolated from ethanol
      treated rats (half-maximal effect, 73 +/- 1 mM K+). When extracellular Ca++ was
      omitted from the incubation medium or the dihydropyridine-type calcium channel
      blocker nitrendipine (10 microM) was added, the increase in [Ca++]i caused by
      depolarization was prevented completely. Thus, these data indicate that chronic
      ethanol treatment in vivo makes L-type voltage-dependent Ca++ channels in Kupffer
      cells easier to open, a phenomenon that could be involved in the mechanism of
      alcoholic liver injury.

PMID- 8263790
TI  - Kappa opioid antagonist effects of systemically administered nor-binaltorphimine
      in a thermal antinociception assay in rhesus monkeys.
AB  - The effects of subcutaneously administered nor-binaltorphimine (nor-BNI; 1.0 and
      3.2 mg/kg) were examined in the warm-water (50 degrees C and 55 degrees C) tail
      withdrawal assay in rhesus monkeys (n = 3). Nor-BNI alone produced variable
      antinociceptive effects in 50 degrees C water up to 3.5 hr after administration
      but was completely ineffective against the 55 degrees C stimulus. Pretreatment
      with nor-BNI under conditions where it was devoid of antinociceptive effects
      produced rightward shifts in dose-effect curves for the kappa opioid agonist
      U50,488 for as long as 14 and 21 days after 1.0 and 3.2 mg/kg of nor-BNI,
      respectively. Under conditions when U50,488 dose-effect curves were shifted, nor
      BNI (3.2 mg/kg) also caused rightward shifts in the antinociceptive dose-effect
      curves of the kappa agonist U69,593 but not in those of the mu agonist alfentanil
      or the kappa agonists [5R-(5,7,8,beta)]N-methyl-N-[7- (1-pirrolidinyl)1
      oxaspiro[4,5]dec-8-yl]4-benzofuranaceta mide, bremazocine, ethylketocyclazocine
      and Mr2033. It is concluded that under the present conditions, nor-BNI acts as a
      selective kappa opioid antagonist with an extremely long duration of action.
      These findings are also consistent with the notion that nor-BNI may antagonize
      only compounds acting at a subtype of kappa opioid receptor.

PMID- 8263791
TI  - Distinct profiles of phosphodiesterase isozymes in cultured cells derived from
      nonpigmented and pigmented ocular ciliary epithelium.
AB  - Alterations in either cyclic AMP (cAMP) or cyclic GMP (cGMP) may modulate the
      production of aqueous humor by the ciliary epithelium of the eye, thereby
      affecting intraocular pressure. We have found distinct profiles of
      phosphodiesterase (PDE) isozyme activity in cultured cells derived from bovine
      pigmented ciliary epithelium (PE) and cells derived from human nonpigmented
      ciliary epithelium (NPE), as well as corresponding differences in the effects of
      selective PDE inhibitors on the accumulation of cAMP and cGMP. In NPE cells, but
      not in PE cells, the major peak of PDE activity was stimulated by Ca++/calmodulin
      stimulated (PDE I), and hydrolyzed both cAMP and cGMP. In contrast, PE cells
      contained a cGMP-specific PDE V not found in NPE cells. Rolipram, a selective
      inhibitor of PDE IV, was more potent and effective than the selective PDE III
      inhibitor CI-930 at potentiating intracellular cAMP accumulation in both cell
      types. Zaprinast, a selective inhibitor of PDE V, potentiated cGMP accumulation
      in PE but not in NPE cells. The results suggest that selective PDE inhibitors may
      modulate aqueous humor production by pigmented and nonpigmented ciliary
      epithelium, the two cell types may have different functional roles, and selective
      modulation of their functions may be possible. Furthermore, there may be distinct
      roles for intracellular calcium in regulating cGMP and cAMP in pigmented vs.
      nonpigmented ciliary epithelial cells.

PMID- 8263792
TI  - Fewer PGE2 and PGF2 alpha receptors in brain synaptosomes of newborn than of
      adult pigs.
AB  - PGE2 and PGF2 alpha decrease cerebral metabolism in the adult but increase it in
      the newborn. The present study was done using synaptosomes from newborn and adult
      pigs to find out whether these diverse cerebral effects of prostanoids are a
      consequence of newborn synaptosomes containing fewer or no EP2 receptors for PGE2
      (mediating cAMP increase and in turn cerebral metabolism decrease) and PGF2 alpha
      receptors [mediating IP3 (inositol 1,4,5-triphosphate) increase and in turn
      cerebral metabolism decrease]. It was found that maximum binding values (fmol/mg
      protein) of [3H]PGE2 and [3H]PGF2 alpha were, respectively, only 11.6 +/- 0.8 and
      8.6 +/- 1.4 on newborn synaptosomes compared with 41.8 +/- 1.8 and 31.2 +/- 4.8
      on adult tissues. EP1 receptors were virtually absent in newborn and adult
      preparations. Practically all the PGE2 receptors on newborn synaptosomes were EP3
      subtype, whereas adult brain synaptosomes contained both EP2 and EP3 subtypes;
      this was indicated by the ability of M&B 28,767, a specific EP3 receptor agonist,
      to cause 100% displacement of [3H]PGE2 binding to synaptosomes of the newborn but
      only 51% in the case of the adult. Also, PGE2, 11-deoxy PGE1 (a nonselective EP2
      and EP3 agonist) and M&B 28,767 (an EP3 agonist) caused comparable decreases in
      cAMP formation in synaptosomes from the newborn, whereas in those from the adult,
      PGE2 and 11-deoxy PGE1 increased and M&B 28,767 decreased cAMP production. PGF2
      alpha markedly increased IP3 synthesis in synaptosomes of the adult but not of
      the newborn.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263793
TI  - Methionine synthase inactivation by nitrous oxide during methionine loading of
      normal human fibroblasts. Homocysteine remethylation as determinant of enzyme
      inactivation and homocysteine export.
AB  - Nitrous oxide inactivates the enzyme methionine synthase by oxidation of enzyme
      bound cobalamin, which is formed from the cofactor methylcobalamin during the
      catalytic cycle. The resulting inhibition of homocysteine remethylation increases
      the homocysteine efflux and thereby the level of extracellular homocysteine, both
      in patients and cultured cells. In the present work we measured the kinetics of
      enzyme inactivation and homocysteine export rate in two human fibroblast cell
      lines exposed to nitrous oxide and cultured in the presence of low to
      supraphysiological concentrations (15-100 microM) of methionine. Both the rate
      and extent of methionine synthase inactivation were reduced by increasing
      methionine concentration in the culture medium. In cells not exposed to nitrous
      oxide, methionine increased the homocysteine export rate in a dose-dependent
      manner. Nitrous oxide increased the export at low methionine concentrations, so
      that for treated cells the export was high and essentially independent of the
      extracellular methionine level. Neither methionine nor nitrous oxide
      significantly affected the amount of S-adenosylmethionine or folate in these
      cells. These data agree with methionine synthase as a low Km and methionine
      conserving enzyme, highlight the importance of methionine synthase activity as a
      determinant of homocysteine export and point to the possibility of protecting the
      enzyme by reducing catalytic turnover through product inhibition.

PMID- 8263794
TI  - KF17837 is an A2 adenosine receptor antagonist in vivo.
AB  - The goal of this study was to determine whether (E)-1,3-dipropyl-7-methyl-8-(3,4
      dimethoxystyryl)xanthine (KF17837) is a useful pharmacological probe for
      investigating in the rat the in vivo physiological roles of A2 adenosine
      receptors. In anesthetized rats, bradycardic responses to N6-cyclopentyladenosine
      and hypotensive responses to 2-[p-(2-carboxyethyl)phenethylamino]-5'-N
      ethylcarboxamido adenosine (CGS21680C) were used to assess A1 receptor and A2
      receptor activation, respectively. After obtaining control responses to N6
      cyclopentyladenosine and CGS21680C, the rats received infusions of either vehicle
      or one of two dosage levels of KF17837, a compound recently demonstrated to be a
      potent and selective A2 receptor antagonist in vitro. KF17837 was infused for 4
      hr and, at various times during the infusions, bradycardic and hypotensive
      responses to N6-cyclopentyladenosine and CGS21680C, respectively, were elicited.
      Infusion of either 10 or 30 micrograms kg-1 min-1 (2.4 or 7.4 mg kg-1 4 hr-1) of
      KF17837 did not significantly affect the bradycardic responses to N6
      cyclopentyladenosine. By contrast, 10 micrograms kg-1 min-1 of KF17837 attenuated
      and 30 micrograms kg-1 min-1 of KF17837 nearly abolished hypotensive responses to
      CGS21680C. In a second study, pretreatment with KF17837 (30 micrograms kg-1 min
      1) did not affect the hypotensive response to either PGI2 (3 micrograms kg-1 min
      1) or acetylcholine (100 micrograms kg-1 min-1); however, it attenuated the
      hypotensive response to adenosine (300 micrograms kg-1 min-1). In a third study,
      hypotension was induced and maintained with an infusion of adenosine (300
      micrograms kg-1 min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263795
TI  - Tolerance to the behavioral effects of chlordiazepoxide: pharmacological and
      biochemical selectivity.
AB  - There is a dynamic interaction between a drug's pharmacological effects and the
      behavioral context in which it is administered. The present study evaluated the
      influence of behavioral processes on the development of tolerance and cross
      tolerance to the rate-decreasing effects of chlordiazepoxide in rats. Sprague
      Dawley rats responded under a fixed-ratio 30 schedule of food delivery. Different
      groups of rats received 18 mg/kg/day of chlordiazepoxide either before (PRE, n =
      8) or after (POST, n = 10) daily experimental sessions for 8 weeks. Cumulative
      dose-response curves for chlordiazepoxide were obtained before and during chronic
      chlordiazepoxide administration and during chronic saline administration.
      Cumulative dose-response curves for midazolam, FG 7142 (N-methyl-beta-carboline-3
      carboxamide) flumazenil, pentobarbital, caffeine, morphine and d-amphetamine were
      determined before, during and 4.5 to 5 months after chronic chlordiazepoxide
      administration. Group PRE developed tolerance to chlordiazepoxide, whereas group
      POST did not develop tolerance. Although cross-tolerance developed to midazolam
      in both groups, it was greater in group PRE. Both groups showed comparable
      sensitization to FG7142 and neither group showed a significant change in
      sensitivity to any of the other drugs. Biochemical studies of gamma-aminobutyric
      acid (GABA)-related functioning in groups of rats that received chronic
      chlordiazepoxide administration either before (BIO-PRE, n = 6) or after (BIO
      POST, n = 6) daily sessions found that GABA-stimulated 36Cl-uptake increased in
      both cortical and cerebellar preparations. However, GABA sensitivity in
      cerebellar tissue was significantly lower in group BIO-PRE compared with group
      BIO-POST. Thus, behavioral tolerance to chlordiazepoxide was associated with both
      pharmacological and biochemical effects, which suggests a relationship between
      behavioral tolerance to benzodiazepines and changes in the functional state of
      the GABA-benzodiazepine receptor complex.

PMID- 8263796
TI  - Immunosuppression by morphine is mediated by central pathways.
AB  - We reported previously that a single systemic injection of morphine (10 mg/kg) to
      rats profoundly suppressed mitogen-induced proliferation of blood lymphocytes by
      a receptor-mediated mechanism. The present study examined whether this
      immunosuppressive effect of morphine is mediated by opioid receptors located at
      either peripheral or central sites. First, the effects of systemic morphine
      administration on analgesia, mitogen-stimulated lymphocyte proliferation and
      corticosterone secretion were compared to those observed after the systemic
      administration of N-methylmorphine, a quaternary derivative which does not
      readily penetrate the blood-brain barrier. In contrast to systemically
      administered morphine, the i.p. injection of N-methyl-morphine (20 mg/kg) was
      without any effect on lymphocyte proliferation, plasma corticosterone
      concentrations or analgesic responses. Secondly, the effects of morphine and N
      methylmorphine after central administration were compared. Within 2 hr after the
      microinjection of either morphine (10 micrograms/2 microliters) or N
      methylmorphine (15 micrograms/2 microliters) into the third ventricle, blood
      lymphocyte responses were inhibited by 70%, plasma corticosterone concentrations
      were significantly elevated and maximal analgesic responses were present.
      Finally, microinjection of morphine (1 microgram/0.2 microliter) into the
      anterior hypothalamus inhibited blood lymphocyte proliferation by 50% without
      producing analgesia or a significant increase in plasma corticosterone. These
      findings suggest that central opioid pathways are involved in the
      immunosuppressive effects of morphine and these pathways may be distinct from
      those participating in opioid-induced analgesia and adrenal activation.

PMID- 8263797
TI  - Protamine and other polycationic drugs inhibit calcium leak in cardiac cells
      during metabolic inhibition and free radical exposure.
AB  - We studied the effect of the polycationic compounds protamine, polybrene and
      gentamicin on the calcium leak induced by metabolic inhibition and free radical
      exposure in cultured neonatal rat cardiac cells. All of the drugs tested
      inhibited the calcium leak. The potency of the compound in this respect was
      related to the magnitude of the positive charge borne by the molecule. Protamine
      was the most potent drug tested. None of the drugs tested had more than a small
      effect on lactate dehydrogenase release. The physicochemical properties of these
      compounds lead us to predict that they are acting at negatively charged sites on
      the outer surface of the sarcolemma. We conclude that polycationic compounds,
      exemplified by protamine, are able to inhibit calcium overload. It is anticipated
      that this group of compounds may be effective as cardioprotective agents.

PMID- 8263798
TI  - Potassium channel openers and blockers: do they possess proarrhythmic or
      antiarrhythmic activity in ischemic and reperfused rat hearts?
AB  - Cromakalim is a member of the new antihypertensive drug family possessing an
      action that involves an increased K efflux in vascular and cardiac muscle. We
      studied the contribution of opening of ATP-sensitive K channel to the development
      of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that
      of Na, K, Ca and Mg in isolated rat hearts. After 30 min of global ischemia,
      cromakalim (1 to 30 microM) failed to reduce reperfusion arrhythmias. On the
      postischemic-reperfused myocardium in a subset of hearts unresponsive to
      reperfusion-induced arrhythmias (duration of ischemia was reduced to 25 min),
      cromakalim treatment was associated with a higher incidence of reperfusion
      ventricular fibrillation (VF) and ventricular tachycardia (VT) as compared to the
      controls (100% VF and 100% VT in treated vs. 41% VF and 50% VT in controls, P <
      .05). Proarrhythmic effects of cromakalim were also reflected in a
      maldistribution of myocardial ions. At concentrations of 3, 10 and 30 microM of
      glibenclamide, a K channel blocker, a significant reduction in the incidence of
      reperfusion-induced VF and VT was observed, and an attenuation in the
      maldistribution of myocardial ion contents induced by ischemia/reperfusion was
      found. The reduction in myocardial contractility was detected at relatively high
      concentrations (10 and 30 microM) in both cromakalim- and glibenclamide-treated
      groups. The proarrhythmic effect of cromakalim (30 microM) was abolished by 3
      microM of glibenclamide, suggesting that the increased tendency to develop
      reperfusion arrhythmias is associated with the cromakalim-induced K
      efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263799
TI  - Adenosine activates afferent fibers in the forearm, producing sympathetic
      stimulation in humans.
AB  - Whereas adenosine is generally considered an inhibitory neuromodulator, there is
      evidence that adenosine may excite a variety of afferent fibers thereby evoking
      sympathetic activation. To determine whether adenosine also excites afferent
      fibers located in the forearm, adenosine was administered into the left branchial
      artery at doses without systemic effects while sympathetic nerve activity was
      monitored through a recording electrode placed in the right peroneal nerve in the
      lower limb. The i.a. adenosine produced a dose-dependent increase in forearm
      blood flow (647 +/- 209% above base line at a dose of 1.5 mg i.a.) and in muscle
      sympathetic nerve activity (97 +/- 30% above base line). No significant effect
      was observed on heart rate or systemic blood pressure. The effects of i.a.
      adenosine were not caused by spill over into the systemic circulation because
      these doses had no effect when given i.v. The increase in sympathetic nerve
      activity was not secondary to the local vasodilatory effects of adenosine because
      nitroprusside, given i.a. at doses that evoked the same degree of vasodilation,
      had no effect on muscle sympathetic nerve activity. The authors interpreted these
      results as indicative of activation of forearm afferent fibers by adenosine. The
      precise nature of these afferent fibers cannot be determined from these studies
      and may include sensory afferents and chemosensitive afferents involved in the
      exercise pressor reflex. By contrast with the known neuroinhibitory actions of
      adenosine in the central nervous system and in efferent nerves, these
      observations are in agreement with the concept that adenosine-induced activation
      of sympathetic afferent fibers is a widespread phenomenon.

PMID- 8263800
TI  - Effects of verapamil on morphine-induced euphoria, analgesia and respiratory
      depression in humans.
AB  - Organic calcium (Ca++) channel antagonists enhance opiate-induced analgesia and
      antagonize respiratory depression produced by morphine in rodents. Our
      preliminary data indicated that verapamil reduces the subjective effects of
      morphine in humans. We therefore assessed morphine-verapamil interactions in 12
      experienced, male polydrug users with histories of heroin abuse by using a double
      blind, cross-over study design. Treatments consisted of two drug infusions.
      Either verapamil, 2.5 or 10 mg, or saline was infused, 30 ml i.v. over 2 min;
      half way through this infusion either 10 mg of morphine or saline was infused, 3
      ml i.v. over 10 sec, via a second catheter. Autonomic parameters, responsiveness
      to pain and subjective self-reports of mood and feeling state were measured over
      4 hr. Analgesia was measured using a finger pressure test and hand immersion in
      ice water. Respiration was measured by using respiratory inductive
      plethysmography and transcutaneous CO2 levels. The Addiction Research Center
      Inventory (ARCI) was used to measure the subjective effects. Morphine had a
      liminal effect on pain threshold, but verapamil potentiated this effect to
      elevate pain threshold significantly. Verapamil did not affect the ability of
      morphine to increase pain endurance or to produce respiratory depression.
      Morphine produced positive affective responses, as demonstrated by elevated
      scores on the Morphine-Benzedrine Group subscale of the ARCI. Verapamil alone
      produced no effects on any ARCI subscales; however, 10 mg of verapamil
      significantly reduced morphine-elevated MBG scores over a 3-hr period. The
      results suggest the euphorigenic and analgesic effects of opioids may be
      differentiated by using Ca++ channel blockers.

PMID- 8263801
TI  - Effects of phenelzine and hydralazine on hydrogen peroxide production and
      proteolysis in human red blood cells.
AB  - The ability of the therapeutic agents phenelzine (PZ) and hydralazine (HD) to
      stimulate the rate of protein degradation and H2O2 production in human red blood
      cells (RBC) was characterized. PZ- and HD-stimulated proteolysis, as monitored
      either by a fluorescence assay or by high-pressure liquid chromatography,
      occurred in a dose-, time- and hematocrit-dependent manner. The more potent PZ
      (0.5 mM), in RBC suspension or hemolysate, stimulated the rate of leucine release
      by 131 and 63%, respectively, whereas HD (1.0 mM) in RBC suspension or hemolysate
      produced increases of 133 and 66% in the rate of leucine release, respectively.
      PZ (0.75 mM) addition to red cells resulted in a rapid stimulation of H2O2
      generation during the first hour of incubation, whereas HD (0.75 mM) addition to
      red cells produced a gradual increase in the rate of H2O2 production over 5 h of
      incubation. Substantial inhibition of PZ- and HD-stimulated proteolysis in RBC
      was observed with N-acetylcysteine, N-ethylmaleimide and the inhibitors of
      methemoglobin reduction, NADP and 2'AMP. In contrast, antioxidants
      dithiothreitol, dimethylthiourea, dimethyl sulfoxide and dimethylfuran had little
      effect on the rates of PZ- and HD-stimulated protein degradation. Western blot
      analysis demonstrated little change in the membrane-bound levels of the calcium
      activated neutral protease calpain after incubation with PZ or HD. However, PZ-
      and HD-stimulated amino acid release was inhibited (approximately 30-50%) by the
      calcium chelator EGTA, suggesting a potential role for calcium-activated neutral
      protease and divalent metal cations in PZ- and HD-stimulated proteolysis.

PMID- 8263802
TI  - Rapid reversal of angiotensin I-induced contractions in rat carotid arteries
      after acute and chronic treatment with the angiotensin-converting enzyme
      inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo- 3S-1H
      1-benzazepena-1-acetic acid (CGS 16617).
AB  - The purpose of these experiments was to determine whether, in carotid arteries
      obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) a
      correlation exists between access of the angiotensin-converting enzyme (ACE)
      inhibitor, 3-[(5-amino-1-carboxy-1S-pentyl)amino]2,3,4,5-tetrahydro-2-oxo-3S- 1H
      benzazepena-1-acetic acid (CGS 16617), to tissue sites and the corresponding
      responsiveness of these tissues to the contractile effect of angiotensin I (ANG
      I). In carotid arteries isolated from SHR and WKY, the magnitude of [14C]CGS
      16617 uptake was slightly greater than the [14C]sucrose uptake (the extracellular
      space), and the percentages of [14C]CGS 16617 and [14C]sucrose in fast and slow
      desaturation components were similar. Addition of high concentrations of
      nonradioactive CGS 16617 (10(-5)M during uptakes or washouts of [14C]CGS 16617
      did not change uptake amounts or efflux rates. The dose-response curves of
      contractions obtained with ANG I or ANG II as well as the dose-dependent
      inhibition of ANG I-induced responses in the presence of CGS 16617 were similar
      for carotids taken from both WKY and SHR. Responses to ANG I were restored as
      early as 5 min after incubation solutions containing inhibitory concentrations of
      CGS 16617 were removed. Similarly, normal responsiveness to the contractile
      effects of ANG I were observed with carotid arteries removed from SHR with
      decreased blood pressure and plasma ACE activity after 5 weeks exposure to CGS
      16617. In contrast, however, responses to norepinephrine were decreased in
      carotid arteries obtained from CGS 16617-treated SHR.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263803
TI  - Modulation of the developing rat sympathetic GABAA receptor by Zn++,
      benzodiazepines, barbiturates and ethanol.
AB  - We have examined the effects of GABA and several GABAA receptor modulators on
      isolated rat (1-160 days) superior cervical ganglion (SCG) neurons with whole
      cell recordings. The neurons were sensitive to GABA within 12 h after birth, and
      the relationship between the current amplitude and GABA concentration (GABA50 =
      19 microM) in these newborn neurons was fitted with a Hill coefficient close to
      1.0. Adult neurons, on the other hand, had a GABA50 value of 30 microM, and the
      slope was steeper and fitted with a Hill coefficient of 1.6. Unlike the results
      of previous studies in cultured SCG neurons, we found that the concentration of
      Zn++ that reduced the response by 50% was 37 +/- 12 microM in newborns and 43 +/-
      6 microM in adults. Bicuculline (10 microM) inhibited the current by 41 +/- 6%
      and 36 +/- 11% in newborn and adult neurons, respectively. With 5 microM GABA,
      diazepam and pentobarbital potentiated the response in newborn and adult neurons.
      No changes were found in the sensitivity of the receptor for these ligands, but
      their efficacy was enhanced 2-fold during development. Diazepam shifted the
      relationship between GABA and the response to the left in all the neurons
      studied. Ethanol (40 mM) reduced the amplitude of the GABA current to 64 +/- 12%
      of control in newborn neurons and to 85 +/- 4% in adult neurons. The inhibitory
      effect of 100 mM ethanol on the GABA current was noncompetitive. Addition of a
      very large concentration of ethanol (850 mM) to newborn neurons potentiated the
      response to 164 +/- 13% of control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263804
TI  - Brain acidosis induced by hypercarbic ventilation attenuates focal ischemic
      injury.
AB  - Intracellular calcium toxicity appears to play a major role in cell death during
      cerebral ischemia. Such calcium enters the cell mainly through the N-methyl-D
      aspartate subclass of the postsynaptic glutamate receptor. Increased
      extracellular hydrogen ion concentration has been shown recently to reduce N
      methyl-D-aspartate-activated divalent cation currents. Therefore, we studied the
      effect of induced brain acidosis, via hypercarbic ventilation, as a potential
      therapeutic modality in focal cerebral ischemia. Brain acidosis reduced infarct
      volume in a biphasic manner, with maximal protection at approximately brain pH
      6.8. The effect was lost at pH 6.5, presumably due to the effect of acidosis on
      glial glutamate uptake.

PMID- 8263805
TI  - 2'-NH2-MPTP in Swiss Webster mice: evidence for long-term (6-month) depletions in
      cortical and hippocampal serotonin and norepinephrine, differential protection by
      selective uptake inhibitors or clorgyline and functional changes in central
      serotonin neurotransmission.
AB  - The i.p. administration of 1-methyl-4-(2'-aminophenyl)-1,2,3,6-tetrahydropyridine
      (2'-NH2-MPTP; 4 x 20 mg/kg) to Swiss Webster mice caused substantial decreases in
      cortical and hippocampal 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid
      and norepinephrine (NE) measured 1 week post-treatment. Compared with the
      authors' previously reported results in C57BL/6 mice, these effects were
      significantly greater in hippocampus (80-90% vs. 60%) and of a similar magnitude
      in frontal cortex (60-75%). A long-term study showed that cortical and
      hippocampal 5-HT, 5-hydroxyindoleacetic acid and NE were still decreased 40% to
      50% 6 months after treatment. Regional brain dopamine was essentially unchanged
      during the 6-month period. Pretreatment with the 5-HT-selective uptake
      inhibitors, fluoxetine or paroxetine, or with the NE-selective uptake inhibitor,
      desipramine, prevented decreases in cortical and hippocampal 5-HT and NE,
      respectively, 3 weeks after 2'-NH2-MPTP (4 x 20 mg/kg). In addition, pretreatment
      with the monoamine oxidase type-A inhibitor, clorgyline, also prevented the more
      modest decreases in 5-HT and NE caused by 4 x 15 mg/kg 2'-NH2-MPTP. Selegiline, a
      monoamine oxidase-B inhibitor, did not provide similar protection. Lastly, 2'-NH2
      MPTP administered 3 weeks earlier, abolished hypothermia caused by the serotonin
      agonist, m-chlorophenylpiperazine, which provided preliminary evidence for an
      associated functional change in the central serotonergic system. Together, these
      data suggest that 2'-NH2-MPTP is a novel agent capable of producing long-lasting
      depletions in forebrain 5-HT and NE but not dopamine in two different strains of
      mice by some mechanisms that resemble those of the parent dopamine-depleting
      neurotoxin, MPTP.

PMID- 8263806
TI  - Gender-associated differences in rat renal tubular amantadine transport and
      absence of stereoselective transport inhibition by quinine and quinidine in
      distal tubules.
AB  - The present studies compared male and female rat renal proximal and distal
      tubular uptake of amantadine, in relation to their transport kinetics and
      enantioselective inhibition by two diastereoisomers, 8S,9R-(-)-quinine and 8R,9S
      (+)-quinidine. Under control conditions, amantadine was concentrated by both
      tubule fractions with a gender difference for distal tubules (tissue:medium
      ratio, 18.0 +/- 1.4 for males and 11.0 +/- 0.6 for females; mean +/- S.E.M., P <
      .05). This was reflected by a higher Km value only in female distal vs. proximal
      tubular tissue (153 +/- 8 vs. 108 +/- 9 microM; P < .01) but decrease in Vmax
      values in distal compared to proximal tubules (P < .01) showed no gender-related
      difference. In proximal tubules, 8S,9R-(-)-quinine and 8R,9S-(+)-quinidine
      competitively inhibited amantadine transport with apparent inhibitory potency of
      2- to 3-fold in favor of 8S,9R-(-)-quinine (P < .01) and without gender
      preference. Conversely in distal tubules, competitive inhibition of amantadine
      transport was also elicited by either 8S,9R-(-)-quinine or 8R,9S-(+)-quinidine at
      a similar concentration range (10-1000 microM), with absence of chiral or gender
      preference. The present transport data have demonstrated an apparent absence of
      stereoselectivity in distal tubular uptake inhibition of amantadine, and are
      suggestive of disparate pathways and/or rate limiting steps involved between
      renal proximal and distal tubular handling of chiral organic cations for both
      genders, and between genders for distal tubular transport of amantadine.

PMID- 8263807
TI  - Dopamine and serotonin release-regulating autoreceptor sensitivity in A9/A10 cell
      body and terminal areas after withdrawal of rats from continuous infusion of
      cocaine.
AB  - The effects of dopamine (DA) and 5-hydroxytryptamine (5-HT) autoreceptor agents
      on electrically induced [3H]DA and [3H]5-HT release from superfused slices of
      striatum, nucleus accumbens and ventral mesencephalon (VM) containing A9 and A10
      neurons were investigated in rats made tolerant to the stimulatory effect of
      cocaine on locomotor behavior by a 14-day continuous infusion of cocaine (29
      mg/kg/day) by s.c. implanted osmotic minipumps followed by a 7-day drug-free
      period. In VM, electrically induced [3H]DA was increased, the ability of
      pergolide to inhibit this release was abolished, but the ability of sulpiride to
      facilitate the release was potentiated, implicating a higher concentration of
      synaptic DA modifying the responsiveness of somatodendritic D2 autoreceptors to
      D2 agents. Both electrically induced [3H]5-HT release from VM and the stimulatory
      effect of in vitro cocaine on this release were enhanced whereas the effects of
      both 5-methoxytryptamine and methiothepin were attenuated, indicating that
      subsensitivity of 5-HT autoreceptors developed in DA cell body regions. In
      striatum and nucleus accumbens, no significant changes were observed in [3H]DA
      and [3H]5-HT release, except for a modest reduction in the effects of both
      pergolide and sulpiride on electrically induced [3H]DA release from striatum.
      These results emphasize the importance of pretreatment-induced changes in DA cell
      body regions, rather than terminal areas, under the present conditions. The
      observed increase in DA autoinhibitory tone and subsensitivity of 5-HT release
      regulating autoreceptors in the VM may contribute to the locomotor tolerance upon
      cocaine challenge after continuous cocaine.

PMID- 8263808
TI  - Prenatal nicotine exposure evokes changes in the incidence and degree of fetal
      electrocortical activation.
AB  - The effects of acute and chronic nicotine (N) administration on fetal
      electrocorticogram (ECoG) were investigated with spectral analysis. Fetal lambs
      were instrumented surgically to permit unanesthetized ECoG monitoring and N
      administration. Acute exposure studies used 4-hr constant-rate infusions at 0.6,
      3 or 10 mg/hr. Chronic exposure studies used continuous infusions at 1.2 mg/hr
      for 7 days. The fast Fourier transform and several derivative parameters were
      used to quantitate the fetal ECoG during both control records and N infusions.
      Four states were identified and quantitated in the control ECoG: high-voltage
      slow activity (State I); low-voltage, fast activity (State IV); and two
      transitional states of intermediate amplitude and frequency. Acute N infusions
      elicited changes in the incidence and degree of electrocortical activation that
      were biphasically dose-related. The 0.6-mg/hr infusion evoked electrocortical
      activation through an increase in the incidence of State IV. Higher infusion
      rates elicited progressively less electrocortical activation. The 3-mg/hr
      infusion affected marginal activation, through a reduction in the incidence of
      State I. The 10-mg/hr infusion elicited mixed activation and depression, as
      assessed by multiple parameter changes. Desensitization of several responses
      diminished the magnitude of depressive effect observed during the 3- and 10-mg/hr
      infusions. Chronic nicotine infusions elicited progressive augmentation of
      electrocortical activation, through increases in the incidence and frequencies of
      State IV. Tolerance to this activating response was not observed.

PMID- 8263809
TI  - Pharmacological characterization of the novel cholinomimetic L-689,660 at cloned
      and native brain muscarinic receptors.
AB  - 1-Azabicyclo[2,2,2]octane,3-(6-chloropyrazinyl)maleate (L-689,660) reportedly is
      an agonist with selectivity for M1 and M3 muscarinic receptors. We confirmed this
      in functional assays of brain muscarinic receptors and of cloned human muscarinic
      receptors transfected into Chinese hamster ovary (CHO-K1) cells. For stimulation
      of phosphoinositide turnover in rat cortical and hippocampal dissociated tissue,
      L-689,660 was a partial agonist (24% and 26% intrinsic activity, respectively,
      relative to oxotremorine-M) with EC50 values of 71 microM and 118 microM,
      respectively. At putative M4 receptors coupled to cyclic AMP inhibition in rat
      striatum, however, L-689,660 acted as a competitive antagonist (KB = 0.4 microM).
      Furthermore, at putative M2/M4 autoreceptors that regulate acetylcholine release
      in the hippocampus, the drug also behaved as an antagonist (KB = 2.1 microM).
      These data indicated that L-689,660 behaves as a postsynaptic agonist/presynaptic
      antagonist at central cholinergic synapses. Further aspects of the selectivity of
      the drug for specific muscarinic receptor subtypes were revealed with
      phosphoinositide turnover assays of cloned muscarinic receptors expressed in CHO
      K1 cells. L-689,660 was a partial agonist at transfected hm1 and hm3 receptors
      and was more potent than oxotremorine-M; however, the drug was inactive at
      transfected hm5 receptors. Partial agonist activity at hm1 and hm3 muscarinic
      receptors was present even after using alkylation to reduce receptor numbers to
      levels comparable to that level found in the hm5 cell line. Thus, with functional
      assays either with brain tissue or with transfected cell lines, L-689,660 was
      shown to be an agonist for the M1 and M3 receptors but not for M5 or M4
      receptors.

PMID- 8263810
TI  - Cholinergic drugs regulate passive avoidance performance via the amygdala.
AB  - The present study was designed to elucidate the role of the amygdala as a site of
      action of muscarinic and nicotinic receptor active drugs in modulating avoidance
      (passive avoidance) and spatial navigation (water maze) performance. Quisqualic
      acid lesioning of the nucleus basalis decreased choline acetyltransferase
      activity in the amygdala and dorsolateral frontal cortex, but not in the
      hippocampus. Single or combined amygdala and nucleus basalis lesions did not
      impair water maze navigation. Combined amygdala and nucleus basalis lesioning did
      not impair passive avoidance performance any more severely than did either of the
      lesions alone. Scopolamine (a muscarinic antagonist) and mecamylamine (a
      nicotinic antagonist) induced a dose-dependent impairment of both passive
      avoidance and water maze performance. The effects of the cholinergic antagonists
      on passive avoidance performance were smaller in amygdala-lesioned rats than in
      the controls. Amygdala lesions did not modulate the effect of the cholinergic
      antagonists in impairing water-maze performance. Nicotine, a nicotinic agonist,
      and arecoline, a muscarinic agonist, restored passive avoidance performance in
      nucleus basalis-lesioned but not in nucleus basalis+amygdala-lesioned rats.
      Nicotine and arecoline did not improve water maze navigation in nucleus basalis
      lesioned or nucleus basalis+amygdala-lesioned rats. The present results suggest
      that the nucleus basalis cholinergic projection may modulate passive avoidance
      performance via amygdaloid muscarinic and nicotinic receptors.

PMID- 8263811
TI  - Nonadrenergic imidazoline binding sites on human platelets.
AB  - Human platelets are shown to possess at least two high-affinity, imidazol(in)e
      preferring binding sites that are pharmacologically distinct from alpha-2
      adrenoceptors. These nonadrenergic sites were radiolabeled even in the presence
      of a 10 microM norepinephrine mask of alpha-2 adrenoceptors. Heterogeneity at the
      nonadrenergic sites was demonstrated by comparing [3H]idazoxan (IDX) binding vs.
      [125I]p-iodoclonidine (PIC) binding. Nonadrenergic [125I]PIC-labeled sites were
      enriched in platelet plasma membranes, whereas the nonadrenergic sites labeled by
      [3H] IDX were codistributed between plasma and internal membranes (nonadrenergic
      [125I]PIC-labeled sites had Bmax = 62 fmol/mg in plasma membranes and 20 fmol/mg
      in internal membranes vs. the [3H]IDX-labeled sites had Bmax = 141 fmol/mg in
      plasma membranes and 192 fmol/mg in internal membranes). Furthermore, competition
      binding studies in the presence of a 10 microM norepinephrine mask revealed major
      (approximately 75%) and minor (approximately 25%) binding components on plasma
      membranes for [125I]PIC. Affinities for the major nonadrenergic [125I]PIC binding
      site were highly comparable to human subtype-I1 imidazol(in)e receptor sites in
      the brain stem (rank order: moxonidine > clonidine > cirazoline > IDX >
      amiloride). However, the minor component of [125I]PIC binding was similar to a
      site reported in kidney, having low affinities for all compounds tested, except
      guanabenz. Finally, a third nonadrenergic internal membrane site, labeled by
      [3H]IDX, was consistent with a subtype-I2 imidazol(in)e receptor site (rank
      order: cirazoline > IDX >> amiloride > moxonidine > clonidine). Thus, based on
      differential subcellular distributions and affinity constants, human platelets
      appear to possess imidazoline receptors (subtype-I1 imidazol(in)e receptor and
      subtype-I2 imidazol(in)e receptor), plus a novel guanabenz-sensitive site, as
      well as an alpha-2A adrenoceptor. These nonadrenoceptor binding sites may explain
      certain novel platelet aggregatory properties previously ascribed to clonidine
      and endogenous clonidine-displacing substance(s), and may serve as markers of
      imidazoline receptors in humans.

PMID- 8263812
TI  - Chloride dependent intracellular pH increase induced by bepridil in human red
      blood cells: a possible involvement in correction of ischemic acidosis.
AB  - Inhibitors of Na+/H+ exchanger are reported to exert an anti-ischemic effect.
      Some calcium antagonists and particularly bepridil are commonly used as anti
      ischemic agents. Therefore, in this study, we test the hypothesis that protective
      effect against ischemia may occur at least in part through an action on Na+/H+
      exchanger. The effect of some calcium antagonists on Na+/H+ exchanger from acid
      loaded and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt
      (DIDS)-treated human red cells (RBC) has been studied with a pHstat technique.
      Doses above those required to affect calcium channel (10(-5) and 10(-4) M) of
      nifedipine, nicardipine, verapamil and diltiazem had no effect on Na+/H+
      exchanger activity. Ethyl isoproply amiloride (10(-4) M) completely inhibited the
      exchanger. Among the calcium antagonists tested, bepridil exhibited a particular
      effect, dissipating the pH gradient independently from the Na+/H+ exchanger
      activity. Bepridil's effect on DIDS-treated RBC was compared with that of a well
      known protonophore, carbamyl cyanide p-(trifluoromethoxy)phenyl hydrazone, and
      with that of tributyltin, which mediates a Cl-/OH- exchange across the cell
      membrane. Bepridil (> 2 x 10(-6) M) acts like tributyltin by dissipating the pH
      gradient whatever the external cation (Na+ or K+) or the membrane potential, and
      its action depends on the ratio intracellular [Cl-]/extracellular [Cl-]. The
      dissipation seems to occur through an OH-/Cl- exchange but other mechanisms may
      intervene. Moreover, intraerythrocytic pH measurement by 31P nuclear magnetic
      resonance clearly showed that bepridil permits the cell to recover normal pH
      faster than control.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263813
TI  - MK-801 temporarily prevents MPTP-induced acute dopamine depletion and MPP+
      elimination in the mouse striatum.
AB  - The acute effects of the noncompetitive N-methyl-D-aspartate (NMDA) receptor
      antagonist 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine [(+)-MK
      801] on 1) dopamine depletion caused by 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP); 2) the biodisposition of the MPTP metabolite 1-methyl
      4-phenylpyridinium (MPP+) and 3) MPTP-induced ATP loss were investigated in the
      mouse striatum. Systemic administration of a single dose of MPTP (40 mg/kg s.c.)
      to C57BL/6 mice rapidly decreased striatal dopamine levels to 30% of control
      values. A single injection of (+)-MK-801 (1 mg/kg i.p.) 30 min before MPTP
      treatment completely prevented striatal dopamine depletion at 1.5 and 4 hr. The
      competitive NMDA antagonist CGS-19755 also completely protected against MPTP
      induced acute dopamine depletion at 4 hr in the striatum. The action of (+)-MK
      801 was only temporary, however, because at 12 hr, the degree of dopamine
      depletion was not different between the (+)-MK-801/MPTP-treated animals and mice
      treated with MPTP alone. Repeated injections of (+)-MK-801 at 4-hr intervals did
      not provide any additional protective effect. (+)-MK-801 administration before
      MPTP exposure did not appear to affect the production of MPP+, but it did
      significantly delay its elimination from the striatum. There was a significant
      correlation between levels of dopamine and MPP+ both in the presence and in the
      absence of (+)-MK-801. Finally, MPTP-induced striatal ATP loss was not affected
      by pretreatment with (+)-MK-801.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263815
TI  - Cardiovascular, thermal and behavioral sensitization to methamphetamine in freely
      moving rats.
AB  - Mean arterial blood pressure (MAP), heart rate (HR), body temperature (BT) and
      locomotive activity (LA) were measured simultaneously after i.p. or i.c.v.
      injection of methamphetamine (MAH) using a biotelemetric system. The system
      enabled us to observe the parameters in freely moving rats under minimum stress.
      MAH (1 mg/kg) given by i.p. injection significantly increased MAP, HR, BT and LA,
      as compared with the saline-control. MAH (5, 50 micrograms) administered by
      i.c.v. injection stimulated responses of HR, BT and LA. After the i.p. injections
      of MAH (1 mg/kg) on days 1, 4, 8, 11 and 15, MAH was administered either through
      i.p. (1 mg/kg) or i.c.v. (50 micrograms) route on day 18. In addition to the LA
      sensitization induced by i.p. and i.c.v. administration of MAH, it was found for
      the first time, to our knowledge, that the repeated i.p. injections potentiated
      the responses of MAP and BT to the subsequent injection of MAH through i.p., but
      not i.c.v., route. The latter finding suggests that the sensitization, produced
      by the repeated i.p. injections, affected responses that MAH induced either
      peripherally or centrally through a peripheral humoral factor or an afferent
      nervous system.

PMID- 8263814
TI  - Characterization of angiotensin II receptors in smooth muscle preparations of the
      guinea pig in vitro.
AB  - Angiotensin II (AII) receptors in guinea pig isolated esophageal muscularis
      mucosae (EMM), stomach fundus, gall bladder, ileum, colon and thoracic aorta have
      been characterized by peptide agonists and nonpeptide antagonists in the presence
      of peptidase inhibitors. Angiotensin peptides contracted every preparation
      studied; the potency order typically was [Sar1]AII > or = AII > angiotensin III
      (AIII) > or = [Val4]AIII >> AI >>> [des Phe8]AII. AI was ineffective everywhere
      except the gall bladder, where it acted as a full agonist. Tetrodotoxin (1
      microM) and atropine (1 microM) did not affect the AII response in EMM, fundus
      and gall bladder. In ileum, AII and AIII were equieffective, and both the maximal
      response and potency were decreased by tetrodotoxin and atropine. Indomethacin (3
      microM) abolished response to AII in the fundus but had little effect on the gall
      bladder and the atropine-resistant component of the ileal response. The AT1
      selective antagonist losartan (DuP 753) antagonized responses to AII in all
      tissues with similar affinities when there was no depression of maximal response
      (pKB = approximately 8-8.3). The AT2-selective antagonist PD123177 (10 microM)
      failed to antagonize responses to AII in any tissue. These data suggest the
      presence of AT1 receptors in intestinal and vascular smooth muscles of the guinea
      pig. It is unclear whether all AT1 receptors are similar because of the
      differential potency order observed in the presence of peptidase inhibitors. Of
      the isolated tissue investigated, responses to AII are robust and reproducible in
      the ileum, fundus and gall bladder.

PMID- 8263816
TI  - YM934, a novel K+ channel opener, activates ATP-sensitive K+ channels in cardiac
      myocytes.
AB  - 2-(3,4-Dihydro-2,2-dimethyl-6-nitro-2H-1,4-benzoxazin-4-yl)pyridin e N-oxide
      (YM934) is a newly synthesized benzoxazin. The effects of YM934 on ATP-sensitive
      K+ (KATP) channels in guinea pig cardiac ventricular myocytes and in an insulin
      secreting cell line, HIT T15 beta-cells, were examined using the gigaohm-seal
      patch-clamp techniques. Under the whole-cell clamp condition, YM934 induced in
      ventricular myocytes a time-independent, glibenclamide-sensitive K+ current in a
      concentration-dependent fashion (EC50 = approximately 3 microM). On formation of
      inside-out patches in ATP-free solution, the KATP channel current abruptly
      appeared and then ran down. YM934 was applied to inside-out patches before,
      during and after channel "run-down." Because nucleoside diphosphates, such as
      uridine diphosphate (UDP), can induce channel openings after complete run-down,
      the effects of YM934 on the UDP-induced channel openings were also examined.
      Before run-down, YM934 enhanced KATP channel activity by decreasing the
      sensitivity of channels to intracellular ATP. YM934 also enhanced the partially
      run-down channel, even in the absence of ATP. After run-down, YM934 had no effect
      but could enhance the UDP-induced KATP channel openings. These effects of YM934
      on cardiac KATP channels were similar to those of pinacidil and lemakalim. In HIT
      T15 beta-cells, 100 microM YM934 was ineffective in both cell-attached and inside
      out patch configurations, suggesting the tissue-specific nature of the action of
      this novel K+ channel opener.

PMID- 8263817
TI  - Tumor necrosis factor-alpha mediates endotoxin-induced lung injury in platelet
      activating factor-primed rats.
AB  - We have reported recently that lipopolysaccharide endotoxin and platelet
      activating factor cooperate in priming relationships to elicit lung microvascular
      injury. Lung injury was associated with elevated serum levels of tumor necrosis
      factor-alpha (TNF alpha) and histological findings highly reminiscent of the
      adult respiratory distress syndrome. The present study was designed to examine
      the role of TNF alpha in lipopolysaccharide/platelet activating factor-induced
      lung injury by utilizing a highly specific monoclonal antibody which block TNF
      alpha actions (anti-TNF alpha monoclonal antibody). Pretreatment with anti-TNF
      alpha monoclonal antibody (2.5-25 mg/kg i.v., n = 5-9) dose-dependently prevented
      the lipopolysaccharide/platelet activating factor-induced histopathological
      changes, lung edema (P < .01), lung myeloperoxidase activity (P < .01), elevation
      of neutrophil count in bronchoalveolar lavage fluid (P < .01) and increased serum
      thromboxane B2 (P < .01). Indomethacin (6 mg/kg i.v., n = 5) failed to modify the
      lung injury despite complete inhibition of thromboxane B2 formation (P < .05).
      These data suggest that TNF alpha might play a key role in initiation of the
      early inflammatory changes which lead to adult respiratory distress syndrome.

PMID- 8263818
TI  - Delta 9-tetrahydrocannabinol inhibition of tumor necrosis factor-alpha:
      suppression of post-translational events.
AB  - Delta 9-tetrahydrocannabinol (delta 9-THC), the major psychoactive component of
      marijuana, has been shown to suppress macrophage soluble cytolytic activity. The
      purpose of this study was to determine whether delta 9-THC inhibited this
      function by affecting tumor necrosis factor-alpha (TNF-alpha). The RAW264.7
      macrophage cell line was used as an in vitro bacterial lipopolysaccharide
      inducible system for production of TNF-alpha. Macrophage-conditioned medium of
      RAW264.7 macrophages treated with delta 9-THC was shown to be deficient in
      tumoricidal activity. Immunoprecipitation experiments demonstrated that the
      macrophage-conditioned medium of cultures treated with drug contained lower
      levels of TNF-alpha. Northern analysis indicated that delta 9-THC had no effect
      on the levels of TNF-alpha messenger RNA. However, radiolabel pulsing and pulse
      chase experiments revealed that the intracellular conversion of the 26-kD
      presecreted form of TNF-alpha to the 17-kD secreted form was inhibited by the
      drug. These results indicate that delta 9-THC suppresses soluble macrophage
      tumoricidal activity, at least in part, by decreasing the intracellular
      conversion of presecretory TNF-alpha to its 17-kD secretory form.

PMID- 8263819
TI  - IL-1 beta modulates the concanavalin-A-induced expression of proenkephalin A mRNA
      in murine thymocytes.
AB  - We have previously shown that proenkephalin A (PEA) messenger RNA (mRNA) is
      induced in murine thymocytes by the T cell-specific mitogen concanavalin-A (Con
      A). We now show that this Con-A-induced expression of PEA mRNA is modulated by
      the cytokine murine interleukin-1 beta (mIL-1 beta) in a biphasic, dose-dependent
      manner. Murine thymocytes were cultured for 72 h with Con-A and with varying
      concentrations of mIL-1 beta. PEA mRNA expression was analyzed by Northern gel
      and solution hybridization techniques. Concentrations of mIL-1 beta of 10(-14)
      and 10(-13) M enhanced the Con-A-induced expression of PEA mRNA in cultured
      murine thymocytes up to 2.5-fold, whereas higher concentrations of mIL-1 beta
      (10(-11) and 10(-10) M) inhibited its expression 60 and 85%, respectively. Both
      the enhancing and inhibiting effects of mIL-1 beta in the Con-A-induced
      expression of PEA mRNA were reversed by a 100-fold excess of interleukin-1
      receptor antagonist protein, but not by a 10-fold excess of interleukin-1
      receptor antagonist protein. The effects of mIL-1 beta on PEA mRNA expression in
      Con-A-activated thymocytes are different from its effects on Con-A-stimulated
      thymocyte proliferation. In the latter case, only enhancement of thymocyte
      proliferation was seen, as measured by [3H]thymidine incorporation. The present
      study demonstrates that PEA mRNA expression is regulated by IL-1 beta, which is
      thought to play a role in thymocyte maturation.

PMID- 8263820
TI  - Achieving prescribed gain/frequency responses with advances in hearing aid
      technology.
AB  - Technological limitations have restricted the capability of older generation in
      the-ear (ITE) hearing aids to closely match prescribed real ear gain/frequency
      responses. Newer technology, widely available in currently marketed ITE hearing
      aids, has considerably improved this capability. Data for 60 ears are presented
      comparing the real ear insertion gain (REIG) actually achieved to the target
      REIG, using ITE hearing aids having: 1) older generation narrow-band receivers,
      and amplifiers with single-pole-filter low frequency tone control and a class A
      amplifier output stage (n = 30), and 2) newer generation amplifiers with a two-
      or four-pole-filter low frequency tone control, and wide band receivers,
      containing a class D amplifier output stage (n = 30). With the newer technology
      ITE hearing aids, the means and ranges of deviation from target gain were
      reduced. Capability for achieving prescription REIG with ITE hearing aids can be
      further improved with multichannel amplifiers. Examples of the latter are shown
      for several difficult-to-fit audiograms.

PMID- 8263821
TI  - Design and evaluation of a continuous interleaved sampling (CIS) processing
      strategy for multichannel cochlear implants.
AB  - Two approaches for representing speech information with multichannel cochlear
      prostheses are being compared in tests with implant patients. Included in these
      studies are the compressed analog (CA) approach of a standard clinical device and
      research processors utilizing continuous interleaved sampling (CIS). Initial
      studies have been completed with nine subjects, seven of whom were selected on
      the basis of excellent performance with the Ineraid clinical processor, and the
      remaining two for their relatively poor performance with the same device. The
      tests include open-set recognition of words and sentences. Every subject has
      obtained a higher score--or repeated a score of 100% correct--on every test when
      using a CIS processor. These results are discussed in terms of their implications
      for processor design.

PMID- 8263822
TI  - Effects of noise and noise reduction processing on the operation of the Nucleus
      22 cochlear implant processor.
AB  - Cochlear implants, like other types of auditory sensory aids, become increasingly
      ineffective with increasing ambient noise levels. One method of signal processing
      to reduce additive random wideband noise, the INTEL method, has been used to good
      effect as an input preprocessor for the Nucleus-22 cochlear implant. The
      implant's own signal processor estimates and encodes pitch frequency and the
      frequencies of Formants 1 and 2. The study reported here shows that additive
      noise results in substantial deviations in formant frequency estimates from those
      that would be observed in the absence of noise. When noisy speech is preprocessed
      by the INTEL method to reduce noise intensity, the deviations in the frequency
      estimates for Formant 2 are substantially reduced.

PMID- 8263824
TI  - Efficiency of dynamic elastic response prosthetic feet.

PMID- 8263823
TI  - Measurements of acoustic impedance at the input to the occluded ear canal.
AB  - Multi-frequency (multi-component) acoustic impedance measurements may evolve into
      a sensitive technique for the remote detection of aural pathologies. Such data
      are also relevant to models used in hearing aid design and could be an asset to
      the hearing aid prescription and fitting process. This report describes the
      development and use of a broad-band procedure which acquires impedance data in 20
      Hz intervals and describes a comparison of data collected at two sites by
      different investigators. Mean data were in excellent agreement, and an
      explanation for a single case of extreme normal variability is presented.

PMID- 8263825
TI  - Behavioral assessment of adaptive feedback equalization in a digital hearing aid.
AB  - An evaluation was made of the efficacy of a digital feedback equalization
      algorithm employed by the Central Institute for the Deaf Wearable Adaptive
      Digital Hearing Aid. Three questions were addressed: 1) Does acoustic feedback
      limit gain adjustments made by hearing aid users? 2) Does feedback equalization
      permit users with hearing-impairment to select more gain without feedback? and,
      3) If more gain is used when feedback equalization is active, does word
      identification performance improve? Nine subjects with hearing impairment
      participated in the study. Results suggest that listeners with hearing impairment
      are indeed limited by acoustic feedback when listening to soft speech (55 dB A)
      in quiet. The average listener used an additional 4 dB gain when feedback
      equalization was active. This additional gain resulted in an average 10
      rationalized arcsine units (RAU) improvement in word identification score.

PMID- 8263826
TI  - Re: Automated Fabrication of Mobility Aids (AFMA): below-knee CASD/CAM testing
      and evaluation program results.

PMID- 8263827
TI  - Intelligibility of frequency-lowered speech produced by a channel vocoder.
AB  - Frequency lowering is a form of signal processing designed to match speech to the
      residual auditory capacity of a listener with a high frequency hearing loss. A
      vocoder-based frequency-lowering system similar to one studied by Lippmann was
      evaluated in the present study. In this system, speech levels in high frequency
      bands modulated one-third-octave bands of noise at low frequencies, which were
      then added to unprocessed speech. Results obtained with this system indicated, in
      agreement with Lippmann, that processing improved the recognition of stop,
      fricative, and affricate consonants when the listening bandwidth was restricted
      to 800 Hz. However, results also showed that processing degraded the perception
      of nasals and semivowels, consonants not included in Lippmann's study. Based on
      these results, the frequency-lowering system was modified so as to suppress the
      processing whenever low frequency components dominated the input signal. High and
      low frequency energies of an input signal were measured continuously in the
      modified system, and the decision to process or to leave the signal unaltered was
      based on their relative levels. Results indicated that the modified system
      maintained the processing advantage for stops, fricatives, and affricates without
      degrading the perception of nasals and semi-vowels. The results of the present
      study also indicated that training is an important consideration when evaluating
      frequency-lowering systems.

PMID- 8263828
TI  - Toward a theory of optimal hearing aid processing.
AB  - An ideal hearing aid for a peripheral hearing loss would process the incoming
      signal in order to give a perfect match between the cochlear outputs of the
      impaired ear and a reference normal ear. As a first step toward this objective, a
      model of the normal and impaired peripheral auditory system was used to derive
      the optimal hearing-aid processing filter based on a minimum mean-squared error
      criterion. The auditory model includes the compression and suppression effects of
      the cochlear mechanics and the sensitivity of the neural transduction process.
      Simplifying assumptions were then incorporated into the processing to yield a
      practical frequency-dependent adaptive gain system. Processing examples of
      several individual speech sounds are presented for a flat hearing loss, and the
      results indicate that a three-channel compression system with adjustable gains
      and band edges will be close to the optimal solution for this case.

PMID- 8263829
TI  - Spectral contrast enhancement of speech in noise for listeners with sensorineural
      hearing impairment: effects on intelligibility, quality, and response times.
AB  - This paper describes a series of experiments evaluating the effects of digital
      processing of speech in noise so as to enhance spectral contrast, using subjects
      with cochlear hearing loss. The enhancement was carried out on a frequency scale
      related to the equivalent rectangular bandwidths (ERBs) of auditory filters in
      normally hearing subjects. The aim was to enhance major spectral prominences
      without enhancing fine-grain spectral features that would not be resolved by a
      normal ear. In experiment 1, the amount of enhancement and the bandwidth (in
      ERBs) of the enhancement processing were systematically varied. Large amounts of
      enhancement produced decreases in the intelligibility of speech in noise.
      Performance for moderate degrees of enhancement was generally similar to that for
      the control conditions, possibly because subjects did not have sufficient
      experience with the processed speech. In experiment 2, subjects judged the
      relative quality and intelligibility of speech in noise processed using a subset
      of the conditions of experiment 1. Generally, processing with a moderate degree
      of enhancement was preferred over the control condition, for both quality and
      intelligibility. Subjects varied in their preferences for high degrees of
      enhancement. Experiment 3 used a modified processing algorithm, with a moderate
      degree of spectral enhancement, and examined the effects of combining the
      enhancement with dynamic range compression. The intelligibility of speech in
      noise improved with practice, and, after a small amount of practice, scores for
      the condition combining enhancement with a moderate degree of compression were
      found to be significantly higher than for the control condition. Experiment 4
      used a subset of conditions from experiment 3, but performance was assessed using
      a sentence verification test that measured both intelligibility and response
      times. Scores on both measures were improved by spectral enhancement, and
      improved still more by enhancement combined with compression. The effects were
      statistically more robust for the response times. When expressed as equivalent
      changes in speech-to-noise ratio, the improvements were about twice as large for
      the response times as for the intelligibility scores. The overall effect of
      spectral enhancement combined with compression was equivalent to an improvement
      of speech-to-noise ratio by 4.2 dB.

PMID- 8263830
TI  - Development and assessment of two fixed-array microphones for use with hearing
      aids.
AB  - Hearing-impaired listeners often have great difficulty understanding speech in
      situations with background noise (e.g., meetings, parties). Conventional hearing
      aids offer insufficient directivity to significantly reduce background noise
      relative to the desired speech signal. Based on array techniques, microphone
      prototypes have been developed with strongly directional characteristics to be
      incorporated into the frame and the "temples" of a pair of eyeglasses. Particular
      emphasis was on optimization and electronic stability. Computer simulations show
      that a directivity index of more than 10 dB can be obtained at the higher
      frequencies. Simulations were verified with free-field measurements. To
      investigate the influence of the human head on directivity, two portable models
      were also tested with a KEMAR manikin. The measurements show that the two models
      give an improvement of the signal-to-noise ratio of approximately 7 dB in a
      diffuse background noise field compared with an omnidirectional microphone. For
      the clinical assessment of these microphone arrays in the diffuse noise field
      (simulating a cocktail party situation), the speech-reception threshold in noise
      for simple Dutch sentences was determined with a normal single omnidirectional
      microphone and with one of the microphone arrays. The results of monaural
      listening tests of 30 subjects with normal hearing and 45 subjects with hearing
      impairment show that the microphone arrays give a mean improvement of the speech
      reception threshold in noise of about 7 dB compared with an omnidirectional
      microphone.

PMID- 8263831
TI  - Properties of an adaptive feedback equalization algorithm.
AB  - This paper describes a new approach to feedback equalization for hearing aids.
      The method involves the use of an adaptive algorithm that estimates and tracks
      the characteristic of the hearing aid feedback path. The algorithm is described
      and the results of simulation studies and bench testing are presented.

PMID- 8263832
TI  - Real-time multiband dynamic compression and noise reduction for binaural hearing
      aids.
AB  - A multi-signal-processor set-up is introduced that is used for real-time
      implementation of digital hearing aid algorithms that operate on stereophonic
      (i.e., binaural) input signals and perform signal processing in the frequency
      domain. A multiband dynamic compression algorithm was implemented which operates
      in 24 critical band filter channels, allows for interaction between frequency
      bands and stereo channels, and is fitted to the hearing of the individual patient
      by a loudness scaling method. In addition, a binaural noise reduction algorithm
      was implemented that amplifies sound emanating from the front and suppresses
      lateral noise sources as well as reverberation. These algorithms were optimized
      with respect to their processing parameters and by minimizing the processing
      artifacts. Different versions of the algorithms were tested in six listeners with
      sensorineural hearing impairment using both subjective quality assessment methods
      and speech intelligibility measurements in different acoustical situations. For
      most subjects, linear frequency shaping was subjectively assessed to be negative,
      although it improved speech intelligibility in noise. Additional compression was
      assessed to be positive and did not deteriorate speech intelligibility as long as
      the processing parameters were fitted carefully. All noise reduction strategies
      employed here were subjectively assessed to be positive. Although the suppression
      of reverberation only slightly improved speech intelligibility, a combination of
      directional filtering and dereverberation provided a substantial improvement in
      speech intelligibility for most subjects and for a certain range of signal-to
      noise ratios. The real-time implementation was very helpful in optimizing and
      testing the algorithms, and the overall results indicate that carefully designed
      and fitted binaural hearing aids might be very beneficial for a large number of
      patients.

PMID- 8263833
TI  - Digital signal processing (DSP) applications for multiband loudness correction
      digital hearing aids and cochlear implants.
AB  - Single-chip digital signal processors (DSPs) allow the flexible implementation of
      a large variety of speech analysis, synthesis, and processing algorithms for the
      hearing impaired. A series of experiments was carried out to optimize parameters
      of the adaptive beamformer noise reduction algorithm and to evaluate its
      performance in realistic environments with normal-hearing and hearing-impaired
      subjects. An experimental DSP system has been used to implement a multiband
      loudness correction (MLC) algorithm for a digital hearing aid. Speech tests in
      quiet and noise with 13 users of conventional hearing aids demonstrated
      significant improvements in discrimination scores with the MLC algorithm. Various
      speech coding strategies for cochlear implants were implemented in real time on a
      DSP laboratory speech processor. Improved speech discrimination performance was
      achieved with high-rate stimulation. Hybrid strategies incorporating speech
      feature detectors and complex decision algorithms are currently being
      investigated.

PMID- 8263834
TI  - Continuing nursing education.

PMID- 8263835
TI  - The use of narcotics in controlling patient pain.

PMID- 8263837
TI  - The use of sequential compression devices in the prevention of deep vein
      thrombus.

PMID- 8263836
TI  - An update on plant-related contact dermatitis.

PMID- 8263838
TI  - Update on epilepsy: the LP/VN's perspective.

PMID- 8263839
TI  - The hazards of chemical dependency among nurses.

PMID- 8263840
TI  - The timing of activity in motor neurons that produce radula movements
      distinguishes ingestion from rejection in Aplysia.
AB  - 1. We have studied the neural circuitry mediating ingestion and rejection in
      Aplysia using a reduced preparation that produces ingestion-like and rejection
      like motor patterns in response to physiological stimuli. 2. We have
      characterized 3 buccal ganglion motor neurons that produce specific movements of
      the radula and buccal mass. B8a and B8b act to close the radula. B10 acts to
      close the jaws and retract the radula. 3. The patterns of activity in these
      neurons can be used to distinguish the ingestion-like and rejection-like motor
      patterns. B8a, B8b and B10 are active together during the ingestion-like pattern.
      Activity in B8a and B8b ends prior to the onset of activity in B10 during the
      rejection-like pattern. 4. Our data suggest that these neurons undergo similar
      patterns of activity in vivo. During both feeding-like patterns, the activity and
      peripheral actions of B8a, B8b, and B10 are consistent with radula movements
      observed during ingestion and rejection. In addition, the extracellular activity
      produced by these neurons is consistent with neural activity observed in vivo
      during ingestion and rejection. 5. Our data suggest that the different activity
      patterns observed in these motor neurons contribute to the different radula
      movements that distinguish ingestion from rejection.

PMID- 8263841
TI  - Circadian changes in cockroach ommatidial structure.
AB  - 1. Morphological correlates of circadian changes in eye sensitivity to light
      measured electrophysiologically were sought in the cockroach, Leucophaea maderae.
      Cross sections of ommatidia removed at subjective midday and subjective midnight
      on 3 successive days from roaches held under constant darkness (DD) at 25 +/- 2
      degrees C were examined using a transmission electron microscope for
      morphological differences related to sampling time. 2. The temporal difference in
      submicrovillar cisternae (SMC) area appeared to exhibit a circadian rhythm,
      however, the amplitude of this temporal difference measured under DD was less
      than that observed under LD 12:12 conditions. SMC areas characteristic at
      nighttime were achieved at subjective midnights but the area diminished only
      partially toward the daytime state on subjective middays. 3. Rhabdom area
      remained constant and the daily rhythm of screening pigment granules (SPG)
      arrangement about the rhabdom was not observed under conditions of constant
      darkness. 4. Results of this study indicate that a pacemaker(s) actively
      influences the change in the SMC toward the nighttime state, whereas, the change
      toward the daytime state results from a passive mechanism that possibly could be
      accelerated by light.

PMID- 8263842
TI  - ABR frequency tuning curves in dolphins.
AB  - Tone-tone masking was used to determine auditory brain-stem response tuning
      curves in dolphins (Tursiops truncatus) in a simultaneous-masking paradigm. The
      Q10 of the curves was as large as 16-19 in the frequency range 64-128 kHz. In the
      range 45-16 kHz, Q10 decreased proportionally to the frequency with the bandwidth
      of the curves being constant, about 3.5-4 kHz at the 10-dB level. Tuning curves
      below 45 kHz are supposed to reflect broad spectral bandwidth of the probe's
      effective part which is no longer than 0.5 ms, irrespective of actual probe
      duration. Tuning curves above 64 kHz are supposed to reflect the real frequency
      tuning of the dolphin's auditory system.

PMID- 8263843
TI  - Thrombocytopenia in cats: a retrospective study of 41 cases.
AB  - The prevalence of feline thrombocytopenia (< 200,000 platelets/microL) at North
      Carolina State University, College of Veterinary Medicine Teaching Hospital, from
      January 1985 to March 1990, was 1.2% (41/3300). Cats were divided into six
      categories based on clinical diagnoses: 29% (12/41) had infectious disease, 20%
      (8/41) had neoplasia, 7% (3/41) had cardiac disease, 2% (1/41) had primary immune
      mediated disease, 22% (9/41) had multiple diseases, and 20% (8/41) had disorders
      of unknown etiology. The mean platelet count for all thrombocytopenic cats was
      52,000/microL +/- 46,000/microL (1 SD) with a range of 1000-190,000/microL. No
      significant differences were found between groups with respect to platelet count,
      packed cell volume, or white blood cell count, though anemia and leukopenia were
      common among the cats as a whole. Bleeding disorders (hemorrhage or thrombosis)
      were observed in 29% (12/41) of thrombocytopenic cats and were more likely to be
      associated with neoplasia, cardiac disease, and platelet counts less than or
      equal to 30,000/microL. Disseminated intravascular coagulopathy was diagnosed in
      12% (5/41) of the cats. Infections and/or neoplasia affecting the bone marrow
      were the most common diseases associated with thrombocytopenia. Feline leukemia
      virus and myeloproliferative neoplasia accounted for approximately 44% (18/41) of
      the specific diagnoses in thrombocytopenic cats.

PMID- 8263844
TI  - Hypophosphatemia and hemolytic anemia associated with diabetes mellitus and
      hepatic lipidosis in cats.
AB  - Hypophosphatemia associated with hemolytic anemia was diagnosed in five cats with
      diabetes mellitus and in one cat with idiopathic hepatic lipidosis. The
      hematocrit began decreasing within 24 to 48 hours after documented
      hypophosphatemia in each case. The anemia resolved in all five surviving cats.
      Because of the temporal relationship and lack of other detectable causes,
      hemolytic anemia was presumed to be caused by hypophosphatemia. There were
      increased Heinz bodies in three of six hypophosphatemic cats during episodes of
      hemolysis. Intravenous potassium phosphate administration corrected the
      hypophosphatemia in four of five cats. The effective dosages of intravenous
      phosphate ranged from 0.011 to 0.017 mmol of phosphate/kg/h for 6 to 12 hours.
      Hypocalcemia (5.4 to 8.7 mg/dL) occurred in four of five cats treated with
      intravenous phosphate; however, only one cat developed clinical signs
      attributable to hypocalcemia. Based on this retrospective study, we recommend
      monitoring serum phosphorus concentration every 6 to 12 hours in cats likely to
      become hypophosphatemic. Treatment of hypophosphatemia in cats is warranted
      because of the apparent increased susceptibility of cats to hypophosphatemia
      induced hemolysis. Cats with severe hypophosphatemia (< or = 1.5 mg/dL) should be
      given oral or parenteral phosphate if contraindications do not exist.

PMID- 8263845
TI  - Spontaneous adult-onset hypothyroidism in a cat.
AB  - Spontaneous adult-onset hypothyroidism, confirmed by a thyroid-stimulating
      hormone stimulation test, thyroid biopsy, and response to replacement therapy, is
      described in a female cat. Clinical signs consisted of profound apathy,
      hypothermia, poor hair growth, severe seborrhea sicca, and a puffy face.
      Cutaneous histological changes consisted of epidermal and follicular
      hyperkeratosis, teloginization of hairs, and dermal mucin deposition. There was
      no adnexal atrophy. Lymphocytic thyroiditis, equivalent to Hashimoto's
      thyroiditis, was shown by thyroid biopsy. Clinical signs rapidly responded to
      thyroxine replacement therapy. Glucose intolerance was coexistent with the
      hypothyroidism, but was not dramatically influenced by thyroxine therapy and
      probably was an independently occurring endocrinopathy.

PMID- 8263846
TI  - Bronchointerstitial pneumonia and respiratory distress in young horses: clinical,
      clinicopathologic, radiographic, and pathological findings in 23 cases (1984
      1989).
AB  - Twenty-three foals, between 1 and 7 months old, with signs of acute respiratory
      distress, were examined at the Veterinary Medical Teaching Hospital (VMTH),
      University of California, Davis, between 1984 and 1989. Characteristic features
      included sudden onset of severe respiratory distress and tachypnea, cyanosis
      unresponsive to nasal oxygen, pyrexia, hypoxemia, hypercapneic respiratory
      acidosis, poor response to treatment, and histopathologic lesions of
      bronchiolitis and bronchointerstitial pneumonia. Seven of the 23 foals were
      normal before the onset of respiratory distress, 3 foals were found dead, and 13
      foals were being treated for respiratory tract infections at the time of
      presentation. Laboratory data obtained for 13 horses showed increased plasma
      fibrinogen concentration (630.7 +/- 193 mg/dL), leukocytosis (18,607 +/-
      7,784/microL), and neutrophilia (13,737 +/- 8,211/microL). Thoracic radiographs
      showed a diffuse increase in interstitial and bronchointerstitial pulmonary
      opacity and, in 5 foals, an alveolar pulmonary pattern of increased density was
      also seen. In 3 foals heavy interstitial infiltration proceeded to a coalescing
      nodular radiographic appearance. Microbiological culture of tracheobronchial
      aspirates (TBA) from 9 foals yielded bacterial growth, but no one bacterial
      species was consistently isolated. Microbiological culture of postmortem
      specimens of the lung from 6 foals yielded growth of bacteria that included
      Escherichia coli, Enterobacter spp., Proteus mirabilis, Klebsiella pneumoniae,
      Rhodococcus equi, or beta-hemolytic Streptococcus spp. Tracheobronchial aspirates
      from 4 foals and lung samples collected from a further 4 foals at necropsy
      yielded no bacterial growth. Cultures were not taken from two foals premortem or
      postmortem. Virologic examination of TBA, lung tissue, or pooled organ tissue
      from 12 foals was negative. Viral culture of TBA from 1 foal showed cytopathic
      effects and positive immunofluorescence for equine herpes virus type II (EHV-II).
      In addition to the 3 foals that were found dead, 11 foals died or were
      euthanatized. Pathologic lesions were limited to the lungs in 50% of the foals;
      the remainder also had bowel lesions suggestive of hypoxic injury. The
      predominant histopathologic pulmonary lesions included bronchiolitis, bronchiolar
      and alveolar epithelial hyperplasia, and necrosis. Many bronchioles were filled
      with mucoid and fibrinocellular exudate. The peribronchiolar interstitium and
      adjacent alveolar spaces were also infiltrated with inflammatory cells and
      contained proteinaceous edema fluid. Type II cell hyperplasia and hyaline
      membrane formation were observed in the majority of foals and in 2 foals alveolar
      multinucleate giant cells were also present.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8263847
TI  - Evaluation of prognostic factors and sequential combination chemotherapy with
      doxorubicin for canine lymphoma.
AB  - Fifty-five dogs with lymphoma were treated using a doxorubicin-based sequential
      combination chemotherapy protocol. Complete response, partial response, and no
      response were seen in 46, 4, and 5 dogs, respectively. The overall median
      remission duration and survival times were 36 and 51 weeks, respectively. Age,
      sex, weight, World Health Organization stage, World Health Organization substage
      (i.e., a = not ill, b = ill), serum calcium concentration, blood urea nitrogen
      concentration, breed and protocol alteration secondary to toxicity were evaluated
      for prognostic significance. Univariate analysis of prognostic factors identified
      sex, World Health Organization substage, and serum calcium as statistically
      significant (P < or = .05) variables for both survival and remission duration.
      Upon multivariate analysis, only substage (P = .036) was a significant prognostic
      factor for remission duration, whereas, both substage (P = .006) and sex (P =
      .005) were significant prognostic factors for survival.

PMID- 8263848
TI  - Plasma endotoxin concentrations in clinically normal and potentially septic
      equine neonates.
AB  - Plasma endotoxin concentrations were measured at 1 to 2 and 5 to 6 days of age in
      clinically normal foals and in potentially septic neonatal foals admitted to
      North Carolina State University's Veterinary Teaching Hospital for a variety of
      conditions. In 1 to 2 and 5 to 6 day old normal foals, median plasma endotoxin
      concentrations were 2.17 (range, 1.61-2.54; n = 6) and 2.89 (range, 2.61-3.50; n
      = 7) endotoxin units/mL (EU/mL), respectively. Median plasma endotoxin
      concentration in potentially septic foals with negative blood cultures or gram
      positive isolates (n = 8) was 2.73 (range, 0.59-4.04) EU/mL. In hospitalized
      foals with gram negative isolates (n = 6), median plasma endotoxin concentration
      was 78.06 (range, 0.76-2,696.41) EU/mL, but individual endotoxin values were only
      increased in foals that were extremely sick and died within hours of sampling.
      Plasma endotoxin concentrations were significantly greater in foals with sepsis
      scores > or = 11 compared with foals with sepsis scores < or = 10. Increased
      plasma endotoxin concentrations appear to predict an unfavorable outcome in
      septic foals, but normal endotoxin concentrations do not appear to have any
      predictive value.

PMID- 8263849
TI  - Radiographic and scintigraphic evidence of focal pulmonary neoplasia in three
      cats with hyperthyroidism: diagnostic and therapeutic considerations.
AB  - Three cats were diagnosed as hyperthyroid based on clinical signs, historical
      findings, laboratory abnormalities, and basal serum thyroxine (T4)
      concentrations, and/or nuclear thyroid scans. Additionally, a presumptive
      diagnosis of thyroid carcinoma with pulmonary metastasis was made in each cat
      based on radiographic or scintigraphic evaluation. All three cats had solitary
      pulmonary nodules 1.5 to 2 cm in diameter on survey thoracic radiographs; one cat
      also had chylous pleural effusion and pulmonary lobar consolidation. Focal
      pulmonary accumulation of sodium pertechnetate (99mTcO4-) and/or radioiodine
      (131I) corresponding to radiographic lesions were seen in all cats. Two cats were
      treated with single ablative doses (1111 to 1480 MBq) of 131I; the remaining cat
      was euthanatized. One of the treated cats died 8 days later; the other cat was
      euthanatized 22 weeks following treatment. Histopathologic examination of tissue
      obtained at necropsy confirmed metastatic thyroid carcinoma in one cat and
      bronchogenic adenocarcinoma in two cats. Our findings indicate that increased
      radionuclide uptake in focal pulmonary lesions and cytologic evaluation of tissue
      obtained by fine-needle aspiration are not specific for thyroid tissue.

PMID- 8263850
TI  - Systemic toxicity associated with doxorubicin administration in cats.
AB  - The systemic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21
      days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Appetite, body
      weight, and the presence of vomiting and/or diarrhea were monitored throughout
      the study. Renal function was monitored by measuring serum blood urea nitrogen
      (BUN) and creatinine concentrations, urine specific gravity, and creatinine
      clearance before each treatment. Electrocardiograms and echocardiograms were also
      done before each treatment. The cats were killed 3 weeks after the last
      treatment, and complete necropsies were performed. Partial or complete anorexia
      occurred in all cats with significant weight loss occurring after a cumulative
      doxorubicin dose of 150 mg/m2 BSA. Mild vomiting and diarrhea that required no
      treatment also occurred sporadically in all cats. Echocardiographic changes
      consistent with doxorubicin-induced cardiomyopathy occurred in four cats after
      cumulative doses of 170 to 240 mg/m2 BSA. Clinical heart disease and
      electrocardiographic changes were not observed. Subsequent histological
      examination revealed myocyte vacuolization and myocytolysis in all six hearts.
      Renal dysfunction, characterized by increasing azotemia with progressively more
      dilute urine, was detected in two cats. Mean creatinine clearance values also
      decreased significantly throughout the study. At necropsy, all cats had
      histological evidence of renal disease.

PMID- 8263852
TI  - Heterogeneity of hypertrophy in feline hypertrophic heart disease.

PMID- 8263851
TI  - Bromide therapy in refractory canine idiopathic epilepsy.
AB  - On a retrospective basis, the response to adding chronic oral bromide (BR) to
      phenobarbital (PB) administration in 23 refractory canine idiopathic epileptics
      between 1986 and 1991 was studied. The mean age for an observed first seizure was
      24 months (range 7 to 72) for all dogs. Thirteen (57%) dogs were males with no
      breed predisposition observed. All dogs were diagnosed as having idiopathic
      epilepsy based on normal metabolic and neurologic diagnostic evaluations. Dogs
      were evaluated before BR therapy for a mean time of 22 months (range 5 to 75
      months). Seventeen dogs (74%) received multiple antiepileptic drugs (AEDs) before
      BR therapy. All animals were maintained on PB at least 4 months before the onset
      of BR therapy, with a mean trough serum concentration of 37.8 mcg/mL and no
      improvement in seizure severity or recurrence. Twelve dogs presented with
      generalized isolated seizures and 11 with generalized cluster seizures (two or
      more seizures within 24 hours) as their first seizure. The effects of BR therapy
      were evaluated for a mean time of 15 months (range 4 to 33), with 17 dogs (74%)
      followed for 12 or more months. The mean BR serum concentration for the 0 to 4
      months time period was 117 mg/dL compared with 161 mg/dL for the greater than 4
      months period. Overall, response to BR therapy was associated with a reduction in
      the total number of seizures in 83% of the dogs when compared with their
      respective pre-BR period. For those followed for 1 year after BR, there was a 53%
      reduction in the number of seizures compared with the previous 12 months.
      Furthermore, owners reported a decrease in seizure intensity (65% of dogs) and
      change to a less severe seizure type (22% of dogs) in those dogs that continued
      to have seizures. Seizure-free status was obtained in 26% of the dogs with
      protection continuing up to 31 months in one dog. No correlations could be
      determined between response to BR and either age of onset of the first seizure or
      interval from the first AED therapy to BR therapy. Adverse effects of concomitant
      BR and PB therapy were polydipsia (56% of dogs), polyphagia (30% of dogs),
      excessive sedation (30% of dogs), and generalized ataxia (17% of dogs). As a
      result of BR treatment, the PB dosage was reduced in eight dogs (35%). In
      conclusion, concomitant BR and PB was well tolerated in dogs of this study and
      was effective in treating refractory canine idiopathic epilepsy, regardless of
      prior interval of seizure activity or previous treatment.

PMID- 8263854
TI  - Research--a personal reminiscence.

PMID- 8263853
TI  - Malta and the British Navy: the medical connection during the nineteenth century.
      Part III. Medical and other problems.

PMID- 8263855
TI  - Climatic and environmental factors in the aetiology of decompression sickness in
      divers.
AB  - As decompression sickness (DCS) may occur unexpectedly after 'safe' dives it was
      hypothesised that the weather and tidal factors could contribute to the risk. One
      hundred and seventy seven cases of DCS were identified from the Institute of
      Naval Medicine's diving accident records and allocated to a 'safe' group or
      control 'risky' group, depending on the dive profiles. Comparison of the
      prevailing environmental conditions between groups revealed significant
      differences in air temperature and windchill (p = < 0.001 for all dives) and for
      air minus water temperature (p = < 0.01 for all dives). The results imply that
      exposure to a cold thermal environment following diving, particularly when the
      air temperature is colder than the water temperature, may be a previously
      unrecognised risk factor for DCS.

PMID- 8263856
TI  - Paediatric resuscitation in adverse circumstances: a comparison of three routes
      of systemic access.
AB  - Nine Kurdish children were admitted to a British Surgical Support Team facility
      in Northern Iraq, requiring resuscitation for dehydration estimated to be of 10%
      loss of body weight. Systemic access was by intravenous (IV, 6 patients),
      intraosseous (IO, 6 patients) and/or intraperitoneal cannulation (IP, 4 patients)
      and resuscitation was according to a defined protocol. Insertion times, maximum
      initial flow rates and complications were assessed. The mean insertion times were
      78, 112 and 26 seconds and the mean maximum initial flow rates of crystalloid
      were 240, 60 and 400 mls/hour for IV, IO and IP routes respectively. One IV
      lasted more than 24 hours and three tissued. One IO cannula blocked, and one IP
      was removed because of saline extravasation. IO bolus injections were painful.
      Total volumes infused and time to adequate hydration varied widely and there were
      no correlations. The mortality was 33%, compared with 11% for 18 less severely
      dehydrated children. It is concluded that the IP and IO routes allow severely
      dehydrated children to be resuscitated without significant complications when IV
      access is difficult to establish.

PMID- 8263857
TI  - Case report: polymorphous haemangioendothelioma, a rare cause of persistent
      lymphadenopathy.

PMID- 8263858
TI  - A clinicopathological survey of gallstones in the autopsy population.
AB  - This prospective study looked at the autopsy prevalence of gallstones and their
      relationship with symptoms and gallbladder pathology. Fifty consecutive autopsies
      were selected. The gallbladder was examined macroscopically and microscopically
      and gallstones were examined, cut and classified. Four females at autopsy had had
      previous cholecystectomies. Thirty three percent of patients had gallstones at
      post-mortem with a male to female ratio of 1:1.24. Histological features of the
      gallbladders were: normal 39.1%, cholecystitis 37.0%, hypertrophy 8.7% and
      fibrosis 15.2%. Increasing age was significantly associated with increasing
      common bile duct (CBD) circumference. Muscle hypertrophy and fibrosis may
      represent part of a spectrum of "burnt out" gallbladder disease. Fifteen percent
      of autopsy patients had calcular cholecystitis but were asymptomatic and the
      reason for this is unclear.

PMID- 8263859
TI  - Student elective USA, November 1992-January 1993.

PMID- 8263860
TI  - The centenary of the sinking of the Mediterranean Fleet flagship, HMS Victoria.
      What was the role of Malta fever?
AB  - This article commemorates the centenary of the tragic loss of the battleship HMS
      Victoria and 358 of her crew, together with the Commander-in-Chief of the
      Mediterranean Fleet, Vice-Admiral Sir George Tryon, as a result of an enigmatic
      order by Tryon himself. It also investigates the medical aspects and explores the
      contention that Tryon was suffering from Malta or Mediterranean fever
      (Brucellosis).

PMID- 8263861
TI  - Influence of maternal age, birth-to-conception intervals and prior perinatal
      factors on perinatal outcomes.
AB  - This study evaluated the influence of prior perinatal factors on birth weight,
      length of gestation, and maternal pregravid and postpartum weights in subsequent
      pregnancies. The study sample included 47 women each with first, second and third
      pregnancies. Mean pregravid weight increased by 5.2 lb between the first and
      second pregnancies and by 4.4 lb between the second and third pregnancies. Total
      weight gain averaged 31 lb for the first pregnancy and 28.4 and 28.3 lb for the
      second and third pregnancies, respectively. Mean birth weight increased by 111 g
      between the first and second pregnancies and by 199 g between the second and
      third pregnancies. Mean gestational age was similar for all three pregnancies,
      averaging 39.5 weeks. Using stepwise forward multiple regression analyses, we
      determined that birth weight and length of gestation are both influenced
      significantly by prior birth weight and length of gestation; subsequent pregravid
      weight is influenced significantly by prior rate of gain, pregravid weight and
      postpartum weight; and postpartum weight is significantly influenced by prior
      rate of gain and birth weight. Comparisons across three pregnancies for the same
      woman showed that differences in birth-to-conception interval were not associated
      with higher postpartum weight or subsequent pregravid weight. These data indicate
      that in healthy, nonsmoking, low-risk women, the maternal and infant outcomes of
      pregnancies are significantly influenced by prior outcomes but not by either
      short birth-to-conception interval or greater maternal age.

PMID- 8263862
TI  - Hysteroscopy: where have we been, where are we going? Honorary luncheon address.
AB  - A quiet resurgence of interest in an old endoscopic technique began in the late
      1960s. Today hysteroscopy, both diagnostic and operative, has become an integral
      part of the gynecologist's technique. The question, "Hysteroscopy: where have we
      been, where are we going?" can be addressed by an examination of the past,
      present and future. Tribute will be paid to the pioneers. The clinical
      applications as practiced today are described. Critical appraisal of the risks
      and benefits of these procedures will permit predictions to be made about the
      future of gynecologic hysteroscopy.

PMID- 8263863
TI  - Laparoscopic supracervical hysterectomy. A comparison of morbidity and mortality
      results with laparoscopically assisted vaginal hysterectomy.
AB  - Laparoscopic applications in hysterectomy promise to be a factor in decreasing
      both economic and medical morbidity. However, with the need for both advanced
      laparoscopic skills and good vaginal surgical techniques, the meaningful
      conversion rate (total abdominal hysterectomy to laparoscopically assisted
      vaginal hysterectomy) appears to be low. A less morbid approach may be subtotal
      hysterectomy, in appropriate candidates, particularly if this procedure is
      readily accomplished by an increased number of physicians. A comparison of
      outcomes in 50 laparoscopically assisted vaginal hysterectomy patients versus 50
      laparoscopic supracervical hysterectomy patients was made, demonstrating that the
      subtotal procedure was significantly less morbid.

PMID- 8263865
TI  - Auditory identification of pelvic blood vessels during laparoscopically assisted
      vaginal hysterectomy. Use of the endoscopic Doppler probe.
AB  - The endoscopic Doppler probe allows instantaneous, audible detection of the
      uterine arteries and other large pelvic blood vessels by simple contact. In
      addition, the Doppler probe reduces the probability of ureteral injury since it
      allows the surgeon to clearly distinguish the uterine artery from the ureter. In
      our experience, the endoscopic Doppler system has effectively reduced the risk of
      bleeding and ureteral injury during difficult laparoscopic hysterectomies in
      which the recognition and safe dissection of the uterine arteries and ureters are
      difficult to achieve.

PMID- 8263864
TI  - Effect of fluid instillation on postlaparoscopy pain.
AB  - One hundred thirty-seven patients participated in a randomized, double-blind
      study to determine what effect instillation of fluid at the conclusion of
      operative laparoscopy has on postoperative postural pain. The first phase
      examined pain intensity as related to closing pH, operative time and the surgeon.
      The second phase focused on the absence or presence of postural pain in the fluid
      and control groups. In phase 1, there was no significant relationship between
      pain and duration of surgery, closing pH or surgeon. In phase 2, 6 of 27 (22%)
      patients receiving postoperative fluid instillation experienced postural pain as
      compared to 19 of 25 (76%) in the control group (P < .001). Displacing the
      pneumoperitoneum by the instillation of 1-2 L of fluid at the conclusion of
      laparoscopy significantly decreased the frequency of subdiaphragmatic and
      shoulder pain on sitting or standing. This pain is probably produced by traction
      on the triangular or coronary ligaments of the liver due to loss of the suction
      effect by the diaphragm.

PMID- 8263866
TI  - Diagnostic and therapeutic conization using loop radiothermal cautery.
AB  - A group of 173 patients with abnormal cervical cytology underwent diagnostic or
      therapeutic conization following colposcopic examination. The series includes 23
      patients with cold knife conization in the hospital under general anesthesia, 12
      patients with an outpatient KTP laser procedure under local anesthesia, 53
      patients with an outpatient CO2 laser procedure under local anesthesia, 10
      patients with hospital-based loop radiothermal cautery conization and 75 patients
      with loop radiothermal cautery conization in the office under local anesthesia.
      Loop radiothermal cautery conization was advantageous, with a shorter duration of
      surgery, lower cost, reduced operative bleeding, less of a need for pain
      relieving medication and shorter duration of postoperative disability. Cold knife
      conization patients had the most intraoperative bleeding and the longest
      hospitalization. KTP laser conization produced specimens of inferior quality,
      resulting in the least satisfactory histologic diagnosis. Office-based loop
      radiothermal cautery conization may be preferable to other methods of conization
      in the diagnosis and management of squamous intraepithelial lesions.

PMID- 8263867
TI  - Cervical removal at hysterectomy for benign disease. Risks and benefits.
AB  - An assessment of the risks and benefits of total and subtotal hysterectomy for
      benign disease was performed using the published literature, including a MEDLINE
      search, on all studies dealing with hysterectomy and related topics from 1946 to
      1992. The shift from subtotal to total hysterectomy occurred before cytologic
      screening was accepted. Currently, SIL is diagnosed by cytology, evaluated by
      colposcopy and treated preferentially with cone biopsy. Prophylactic removal of
      the cervix does not eliminate the risk of cancer: it may shift the risk to the
      vaginal epithelium. The cervix has a role in sexual arousal and orgasm, probably
      due to stimulation of the Frankenhauser uterovaginal plexus. Bladder and bowel
      dysfunction following total hysterectomy may be related to loss of nerve ganglia
      closely associated with the cervix. Increased operative and postoperative
      morbidity, vaginal shortening, vault prolapse, abnormal cuff granulations and
      oviductal prolapse are other disadvantages of total hysterectomy. The cervix is
      not a useless organ and should not be removed during hysterectomy without a
      proper indication.

PMID- 8263868
TI  - Artificial urinary sphincter for recurrent/severe stress incontinence in women.
      Urogynecologic perspective.
AB  - Eight American Medical Systems 800 artificial urinary sphincters were implanted
      in seven women with severe and/or recurrent stress urinary incontinence. The
      surgical approach to urethral cuff implantation consisted of both abdominal and
      combined abdominal and vaginal approaches. Indications, preoperative evaluations,
      surgical technique and complications are discussed. Postoperative follow-up for 6
      24 months showed all the patients to be completely continent subjectively and
      objectively. The artificial urinary sphincter is a viable option in these
      difficult cases of urinary incontinence.

PMID- 8263869
TI  - Prevalence of beta-lactamase enzyme production in bacteria isolated from women
      with postpartum endometritis.
AB  - One hundred eighty-four postpartum patients with the diagnosis of endomyometritis
      underwent intrauterine culturing. Beta-Lactamase production was tested using
      nitrocephin-impregnated discs in 278 bacterial isolates from patients with
      postpartum endometritis. beta-Lactamase production was found to be present in 149
      of 278 (54%) isolates tested: 0 of 39 Streptococcus faecalis (0%), 22 of 41
      Escherichia coli (54%), 66 of 68 Bacteroides bivius (97%), 0 of 13 Proteus
      mirabilis (0%) and 15 of 42 Staphylococcus epidermidis (36%). Anaerobes, as a
      group, had the highest rate of beta-lactamase production, 94 of 102 (93%),
      followed by gram negatives, 34 of 84 (40%), then gram positives, 21 of 91 (23%).
      However, it was the beta-lactamase produced by the gram-negative bacteria that
      was most responsive to the addition of a beta-lactamase inhibitor. The frequent
      isolation of beta-lactamase-producing bacteria from patients with postpartum
      endometritis raises concern about the use of antibiotics not resistant to these
      enzymes. Therefore, antibiotics combined with a beta-lactamase inhibitor may have
      potential as single-agent therapy in obstetric and gynecologic infections.

PMID- 8263870
TI  - Relationship between C-reactive protein levels and intraamniotic infection in
      women with preterm labor.
AB  - The purpose of this study was to determine the relationship between C-reactive
      protein (CRP) levels and intraamniotic infection in 48 women presenting with
      preterm labor and intact membranes. Blood samples for CRP tests were obtained
      immediately before the performance of transabdominal amniocentesis. The
      prevalence of amniotic fluid cultures positive for organisms was 14.6%. In 16
      women (33.3%) positive CRP levels were obtained. There were no significant
      differences in the prematurity rate or the prevalence of microbial invasion of
      the amniotic cavity between women with positive CRP levels and women with
      negative levels. The sensitivity, specificity, and positive and negative
      predictive values for the detection of amniotic infection were 71.5%, 73.2%,
      31.3% and 93.8%, respectively. Based on these results, we suggest that in women
      with preterm labor and negative CRP levels, routine amniocentesis may not be
      essential to the initial workup.

PMID- 8263871
TI  - Incidence of fetal loss in infertility patients after detection of fetal heart
      activity with early transvaginal ultrasound.
AB  - A study was conducted to determine the incidence of fetal loss after fetal heart
      activity (FH) had been detected with vaginal ultrasound. One hundred sixty
      patients with serum beta-human chorionic gonadotropin greater than 25 mIU/mL were
      studied. Patients underwent serial vaginal ultrasound evaluations every one to
      two weeks beginning the 5th week from the last menstrual period (LMP), through 12
      weeks. One hundred fourteen (71%) patients had confirmation of FH (mean days from
      LMP, 48.1 +/- 2.9 SD). Of these, 106 (93%) patients had normally progressing
      pregnancy, while 8 (7%) experienced a fetal loss in the first trimester. There
      were no significant differences in fetal wastage after unstimulated cycles (n =
      30), clomiphene citrate cycles (n = 24), human menopausal gonadotropin (hMG)
      cycles (n = 27) and gonadotropin releasing hormone agonist/hMG cycles (n = 33).
      Although mean gestational age at which post-FH fetal loss was diagnosed was 67.2
      +/- 7.2 days, only two of the losses occurred after 65 days (1.7%). The
      probability of a pregnancy loss after the detection of FH is approximately 7%,
      and fewer than 2% of pregnancies with previously documented FH may have a fetal
      loss after nine weeks.

PMID- 8263872
TI  - Ectopic pregnancy. Diagnostic and therapeutic algorithms minimizing surgical
      intervention.
AB  - Presented are the results of a diagnostic algorithm for ectopic pregnancy
      incorporating history, physical examination, quantitative human chorionic
      gonadotropin (hCG), serum progesterone, color-flow vaginal Doppler sonography and
      endometrial curettage as well as a treatment algorithm combining expectant,
      medical and surgical management. These algorithms resulted in: (1) earlier
      diagnosis of ectopic pregnancy, with fewer ruptured ectopic pregnancies; (2)
      virtual elimination of diagnostic laparoscopy; (3) elimination of culdocentesis;
      (4) greater use of methotrexate; and (5) increased use of expectant (i.e.,
      nonsurgical and nonmedical) treatment. These algorithms are potentially
      applicable in other clinical settings and should be considered for use on at-risk
      populations or when the diagnosis of ectopic pregnancy is in question.

PMID- 8263873
TI  - Acute pericarditis with a symptomatic pericardial effusion complicating
      pregnancy. A case report.
AB  - A 30-year-old, white woman, gravida 4, para 2, abortus 1, was hospitalized at 21
      weeks' gestation because of a symptomatic pericardial effusion. Extensive
      evaluation including pericardial biopsy failed to reveal a specific cause.
      Treatment with pericardiotomy and intrapericardial hydrocortisone was followed by
      relief of symptoms. The remainder of the pregnancy was uneventful. Idiopathic
      pericardial effusion in pregnancy is a rare problem, and the proper approach to
      evaluation and treatment is not known. We present an approach that resulted in a
      favorable outcome.

PMID- 8263874
TI  - Multifocal endometriosis. A case report.
AB  - Disseminated endometriosis of the urinary, genital and intestinal systems was
      treated successfully with conservative surgery. We hypothesize that this unusual
      presentation may have derived from retrograde menstruation, pooling of
      endometrial cells in the dependent anterior and posterior cul-de-sacs with
      subsequent passage across the peritoneal mesothelium, and dissemination by
      clockwise intraabdominal currents.

PMID- 8263875
TI  - Human papillomavirus, type 16, DNA in multicentric anogenital neoplasia
      associated with idiopathic panmyelopathy. A case report.
AB  - A 27-year-old woman suffering from panmyelopathy for six years presented with a
      cervical low grade squamous intraepithelial lesion (SIL), vulvar high grade SIL
      and perianal squamous cell carcinoma with an inguinal metastasis. Southern blot
      hybridization with 32P-labeled human papillomavirus (HPV) DNA revealed HPV 16 DNA
      in varying copy numbers in material from the four locations. HPV 16 genomes
      persisting after surgery on the perianal tumor area were no longer detectable
      after betatron radiotherapy.

PMID- 8263876
TI  - Complications from permanent suture in surgery for stress urinary incontinence. A
      report of two cases.
AB  - Two cases reports are used to illustrate potential complications of permanent
      suture in vaginal and abdominal surgical procedures for urinary incontinence. The
      first case used permanent suture for an abdominal retropubic urethropexy. A
      portion of a glove finger remained attached to the suture and was not recognized
      until the patient developed a retropubic abscess two years later. In the second
      case, permanent suture used in a vaginal retropubic urethropexy eroded through
      the vagina. The patient presented with lower abdominal pain 18 months after the
      procedure; the pain was relieved with removal of the suture. Complications of
      using permanent suture in abdominal retropubic urethropexy have not been
      reported, but the attachment of a foreign body, such as a glove finger, can
      create an adverse outcome. The use of permanent suture in vaginal procedures
      should be used with the awareness that there are potential complications.

PMID- 8263877
TI  - Pelvic schwannoma in pregnancy. A case report.
AB  - Schwannomas are benign nerve sheath tumors that may originate at any anatomic
      site. Usually they are found on the peripheral nerves of the head, neck or flexor
      surfaces of the upper extremities. Rarely does a schwannoma originate in the
      pelvis and present as a retroperitoneal pelvic mass. Only two previous cases of a
      pelvic schwannoma complicating pregnancy have been presented in the English
      language literature. We present a third case.

PMID- 8263878
TI  - Wilms' tumor of the uterus. A case report.
AB  - Extrarenal Wilms' tumors (nephroblastomas) are considered rare, with only 36
      cases reported to date. A primary Wilms' tumor of the uterus has been reported on
      two previous occasions. A third case is presented and the histologic features and
      histogenesis of the tumor discussed.

PMID- 8263879
TI  - Laparoscopic cholecystectomy in the second trimester of pregnancy. A case report.
AB  - Laparoscopic cholecystectomy was performed at 19 weeks' gestation for recurrent
      cholecystitis. The procedure was completed without complications, and the patient
      was discharged on the second postoperative day. Thereafter, the pregnancy
      progressed uneventfully.

PMID- 8263880
TI  - Diabetes insipidus and acute fatty liver. A case report.

PMID- 8263881
TI  - Blood pressure in subjects from rural Greece, comparing individuals migrating to
      Melbourne, Australia with non-migrant relatives.
AB  - The aim of the study was to compare the systolic and diastolic blood pressures in
      525 individuals who had migrated from rural Greece to Melbourne, Australia with
      those in 367 nonmigrant relatives (all aged 30 to 59 years and still living in
      the source area), and to relate any differences to previously identified
      correlates of BP. This migrant family design offers enhanced environmental
      heterogeneity while controlling in large part for genetic and other familial
      factors. Migrating siblings differed from nonmigrating siblings on some variables
      determined at the time of migration but these were not independently associated
      with BP. Migrants had been in Australia for an interquartile range of 19 to 25
      years. DBP was higher in migrants by 4.57 (+/- 0.97) mmHg for males and 2.66 (+/-
      0.86) mmHg for females. SBP was not different at age 30 years but increased more
      steeply with age in the migrants: 0.89 (+/- 0.17) mmHg/yr vs. 0.41 (+/- 0.13)
      mmHg/yr in males and 1.18 (+/- 0.14) mmHg/yr compared with 0.83 (+/- 0.15)
      mmHg/yr in females. Significant associations, independent of age, were found only
      with body mass index and ambient temperature at the time and place of
      measurement. There was no consistent association with alcohol despite a wide
      range of exposures, with dietary and psychosocial variables, or with length of
      residence independent of age. The higher body mass index of and lower ambient
      temperatures for migrants accounted for differences in mean DBP but not in SBP.
      Proportions defined as hypertensive were similarly associated only with migrant
      status, body mass index and temperature. Pressures in Greece were substantially
      below predictions derived from the Intersalt data set, suggesting unidentified
      protective factors.

PMID- 8263882
TI  - Blood pressure and life style in the People's Republic of China: three samples in
      the INTERSALT Study.
AB  - In INTERSALT, the International Cooperative Study on Electrolytes and Blood
      Pressure, three centres located in the People's Republic of China (PRC) had
      distinctive patterns of BP and of life style variables that, in INTERSALT
      overall, were found to relate to BP. The PRC centres had low body mass index
      (BMI) and alcohol consumption but high urinary sodium and sodium/potassium ratio
      (Na/K). Compared with 45 other INTERSALT centres, average BMI was 22.7 vs. 25.4
      and alcohol consumption was 32% vs. 61%, with heavy drinking 3% vs. 14%. However,
      Na/K in the PRC was 6.7 vs. 3.2 in the other centres. This combination of factors
      may underlie the BP pattern observed. While mean BP in the PRC was lower than in
      the 45 centres (-7.0 mmHg SBP, -5.6 mmHg for DBP), this was counterbalanced by
      other findings. Upward slope of systolic pressure with age was 45% greater for
      the PRC than the other centres and 24% greater for diastolic pressure. As a
      result, although percentage hypertensive for ages 20-49 years for the PRC was
      half that in the 45 centres (6% vs. 12%), by age 50-59 years the prevalence was
      31% in the PRC and 38% in the other centres. Hypertension prevalence in Tianjin,
      with highest Na/K in INTERSALT (7.6) was 40% for ages 50-59 years. While sample
      size in individual centres does not provide power to demonstrate aetiological
      relationships, these findings permit formulation of the following hypothesis:
      although lower body mass and lower alcohol intake may counteract to some degree
      impact of high salt intake, such intake over decades eventually takes its toll on
      BP.

PMID- 8263883
TI  - Sex and ethnic differences associated with urinary sodium and potassium in
      African-American US white and Nigerian college students.
AB  - BP and urinary sodium and potassium were assessed in 183 African-American, 113 US
      white and 72 Nigerian college students. SBP was higher in African-American males
      compared with Nigerian and US white males (123.1, 117.6 and 115.7 mmHg,
      respectively, P < 0.05). There were no significant differences observed between
      African-American and white male students in overnight urinary excretion rates of
      sodium and potassium. In contrast, African-American females excreted more sodium
      (41.0 vs. 31.3 mEq per 8 hours, P < 0.01) and potassium (12.0 vs. 8.9 mEq per 8
      hours, P < 0.05) compared with white females. Only among the white students was a
      significant sex difference observed in urinary electrolyte excretion rates, where
      males excreted at higher rates than females. Multiple regression models for the
      African-Americans revealed that potassium explained only 4% of the SBP variance.
      Among the US whites and Nigerians, sodium explained 4.9% and 6.8%, respectively,
      of the DBP variance.

PMID- 8263884
TI  - Hypertension and end-stage renal failure in tropical Africa.
AB  - We report clinical data and autopsy renal histology in 78 patients who died from
      chronic renal failure in Ghana. There were 78 patients, 54 male and 24 female,
      and the majority were aged between 20 and 50 years. The major causes of chronic
      renal failure were hypertensive renal damage (38 patients) and chronic
      glomerulonephritis (33 patients). The most common glomerular lesion leading to
      end-stage renal failure was a focal segmental sclerosing glomerulonephritis. It
      is possible that some of these segmental sclerosing glomerular lesions were
      secondary to glomerular hyperfiltration caused by reduced renal mass from
      hypertension-induced glomerular ischaemia. A public health programme leading to
      better awareness of the importance of detecting hypertension and having this
      treated could be a major contribution to reducing by at least half the number of
      deaths from renal failure reported here.

PMID- 8263885
TI  - Randomised double-blind comparative study of efficacy and safety of
      hydroflumethiazide and reserpine and chlortalidone and atenolol in the treatment
      of mild to moderate hypertension in black patients.
AB  - This randomised, double-blind study compared the efficacy and safety of a fixed
      combination of hydroflumethiazide 50 mg and reserpine 0.125 mg (H-R) and
      chlortalidone 12.5 mg and atenolol 50 mg (C-A) in adult black patients with mild
      to moderate hypertension (a resting supine diastolic blood pressure (DBP) between
      95 and 115 mmHg after a two week placebo washout period). If the DBP did not
      reach 90 mmHg after four weeks, the dosage was doubled. There were 27 patients in
      the H-R group and 22 in the C-A group who completed the study. In the H-R group,
      supine systolic and diastolic BP were reduced from 156.5 (95% confidence
      intervals 150.1-162.9) and 102.0 (97.5-106.5) mmHg to 137.0 (130.6-143.4) and
      87.4 (83.0-91.9) mmHg, respectively. The corresponding values in the C-A group
      were 154.1 (147.0-161.2) and 103.4 (98.5-108.4) mmHg to 136.4 (129.3-143.5) and
      91.2 (86.2-96.1) mmHg, respectively. Normalisation, response and control of DBP
      was achieved in 88.9, 92.6 and 100% of patients, respectively, in the H-R group,
      and in 81.8, 95.5 and 95.5% of patients in the C-A group, respectively. The dose
      was doubled in 14.8% of patients on H-R and 40.1% on C-A. No clinically
      significant abnormalities in laboratory variables and no serious adverse effects
      were encountered. Both drugs have been shown to be efficacious and safe in the
      treatment of mild to moderate hypertension in black patients.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8263886
TI  - Relative role of genes and environment on BP: twin studies in Madras, India.
AB  - This study was conducted to test the feasibility of the twin research model in a
      developing country with diverse cultures and to understand the relative influence
      of genetic and environmental factors on BP variation among South Indians. This
      was a cross-sectional twin study of volunteers using a two-by-two factorial
      design for the analysis of quantitative traits. The factors were twin type
      (monozygotic and dizygotic) and sex (male and female). The study was conducted in
      Madras. Twenty-four pairs of twins were contacted for participation in the
      project. Of the 24 pairs we contacted, 91% (20) actually participated in our
      study. Among 20 sets we studied, 10 (50%) are males and 10 (50%) are females with
      an average age of 23 years. The mean SBP of this volunteer twin population was
      115.18 +/- 1.27 mmHg and DBP was 68.53 +/- 1.41 mmHg. Analysis of dietary habits
      (vegetarian/nonvegetarian) showed that BP was greater (118.26 +/- 2.29/71.88 +/-
      2.34 mmHg) in vegetarian twins than nonvegetarians (112.28 +/- 1.42/66.2 +/- 1.90
      mmHg). Also a positive correlation between urinary excretion of calcium and BP
      was observed. The present study demonstrates that epidemiological research in a
      developing country like India is feasible and economical, using the twin research
      methodology. As observed in other populations, the major source of BP variation
      in the population appears to be predominantly under genetic control.

PMID- 8263887
TI  - Discordance of mercury sphygmomanometer and ambulatory blood pressure
      measurements for the detection of untreated hypertension in a population study.
AB  - To evaluate the extent to which ambulatory blood pressure (ABP) measurements
      could redefine the prevalence of untreated hypertension in the general
      population, we studied a randomly selected subgroup of the National Heart
      Foundation of Australia's Risk Factor Prevalence Study 1989. Subjects taking
      blood pressure (BP) lowering medications were excluded, leaving 66 patients with
      24h ABP recordings for analysis. Mean awake ABPs were generally lower than survey
      BPs and diminished with reduced activity (away from work and during sleep). The
      correlation of survey BP and daytime ABP (10.00-20.00 h) classification of
      untreated hypertension was moderate (Cohen's correlation coefficient 0.49-0.56).
      Untreated hypertension was identified in 20 subjects by the mercury
      sphygmomanometer technique (BP > or = 150/90 mmHg). Six (30%) of those subjects
      had a mean ABP < 135/85 mmHg suggesting 'normotension' on ambulatory criteria.
      Conversely, 19 subjects had a mean ABP of > or = 135/85 mmHg, five (26%) of whom
      had 'normal' survey BPs. We conclude that ambulatory and mercury sphygmomanometer
      methods of BP measurement in this population study defined a similar prevalence
      of untreated hypertension but were discordant for a substantial percentage of
      individuals. The prognostic significance of ABP levels and any discordance with
      survey or office mercury sphygmomanometer BP readings will remain uncertain until
      prospective studies using both forms of measurement are completed.

PMID- 8263888
TI  - Prevalence of left ventricular hypertrophy as assessed by electrocardiogram in
      treated hypertensive persons in general practice.
AB  - Many studies have paid attention to the prevalence of left ventricular
      hypertrophy (LVH) as assessed by electrocardiogram (ECG) in hypertensive
      patients. Patients with ECG-LVH show a considerably higher risk of cardiovascular
      morbidity and mortality than patients without ECG-LVH. This paper describes the
      prevalence of LVH and the relation between LVH, age, sex and BP. ECG, BP,
      treatment, duration of hypertension, body mass index and total serum cholesterol
      were recorded. The dimension of LVH was computed in accordance with the Minnesota
      Code. One of five hypertensive patients (21%) had LVH with or without
      repolarisation abnormalities. LVH based on high QRS voltages only was found more
      often in men. LVH with repolarisation abnormalities was more frequent in elderly
      patients. LVH was found more often in the highest SBP categories (SBP > 160 mmHg)
      and in the highest DBP categories (DBP > 105 mmHg). A logistic regression
      analysis showed the influence on the occurrence of LVH of the following
      parameters: being male, age > 65 years, SBP > 160 mmHg and DBP > 105 mmHg.

PMID- 8263889
TI  - Effects of antihypertensive therapy on left ventricular hypertrophy of essential
      hypertension: a role for insulin-like growth factor I?
AB  - In a previous work we have found than an association exists between the presence
      of left ventricular hypertrophy (LVH) and increased circulating levels of insulin
      like growth factor I (IGF-I) in essential hypertension. To address whether this
      association is of pathophysiological relevance the relationship between
      echocardiographically determined LVH and IGF-I levels was investigated in 49
      patients with essential hypertension before and after one year of
      antihypertensive treatment with different regimens (nonpharmacological measures,
      bisoprolol, captopril). The control group consisted of 30 normotensive subjects
      without LVH. Before treatment IGF-I levels were higher (p < 0.05) in
      hypertensives with LVH, n = 17, (81.3 +/- 14.3 ng/ml) compared with hypertensives
      without LVH, n = 32, (57.4 +/- 3.9 ng/ml) and controls (61.3 +/- 3.9 ng/ml). A
      positive correlation was found between IGF-I levels and LVMI in the whole group
      of hypertensives (r = 0.32, p < 0.05). After one year of treatment hypertensives
      with initial LVH separated in two subgroups: those in which LVH regressed (n =
      10) and those in which LVH persisted (n = 7). A similar diminution of BP was
      observed in the two subgroups of hypertensives. The IGF-I levels decreased
      significantly in patients in which LVH regressed (101.6 +/- 21.7 vs. 61.2 +/- 8.5
      ng/ml; p < 0.05) and increased slightly in patients in which LVH persisted (51.2
      +/- 8.9 vs. 68.5 +/- 7.9 ng/ml). Six patients in which LVH regressed showed a
      diminution of IGF-I after treatment. These six patients had received captopril as
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263891
TI  - Percutaneous transluminal renal angioplasty in the management of hypertension and
      renal failure in patients with renal artery stenosis.
AB  - Percutaneous transluminal renal angioplasty (PTRA) is an accepted method of
      treatment of hypertension resulting from renal artery stenosis. There is less
      information on the role of PTRA in patients with renal artery disease and renal
      impairment. We report on 30 patients who underwent PTRA for renal artery stenosis
      (13 had uncontrolled hypertension and normal renal function and 17 had
      hypertension and renal insufficiency; 26 patients had atheromatous disease,
      fibromuscular dysplasia was diagnosed in 2 and 2 patients had renal artery
      stenosis to a transplant kidney). These 30 patients had 43 PTRA procedures, with
      the 'initial technical success' rate of 81% and the 'overall success' rate of 79%
      after ten months. Results of renal PTRA on BP showed the initial benefit in 88%
      of patients: 71% 'cured' and 17% 'improved'. After ten months only 38% of
      patients could still be considered 'cured' and 33% 'improved'. Renal function
      'improved' in 68% of patients who presented with renal insufficiency. An
      improvement of BP control or renal function was less likely in patients with
      bilateral severe atheromatous disease. PTRA is an effective treatment for renal
      artery stenosis. Satisfactory improvement of BP control and improvement or
      prevention of further deterioration of renal function may be achieved in a high
      proportion of patients.

PMID- 8263890
TI  - Cardiovascular response and red cell membrane sodium transport in hypertensive
      cardiac hypertrophy.
AB  - To investigate the involvement of the sympathetic nervous system and cell
      membrane sodium transport in hypertensive cardiac hypertrophy, we divided 51
      middle-aged male patients with essential hypertension into cardiac hypertrophy
      and noncardiac hypertrophy groups. We then compared the plasma noradrenaline
      concentration after exercise, the cardiovascular response to exercise and
      sympathomimetic agents, and cell membrane sodium transport in the two groups.
      There were differences between the cardiac hypertrophy and noncardiac hypertrophy
      groups with regard to the pressor response to exercise and noradrenaline (i.e.
      the response to sympathetic alpha-receptor stimulation) as well as the
      intracellular sodium concentration and cell membrane sodium transport. We
      concluded that there were abnormalities of the pressor response to alpha-receptor
      stimulation and of intracellular sodium concentration and cell membrane sodium
      transport in patients with hypertension and cardiac hypertrophy. These
      abnormalities might play some role in the pathogenesis of hypertensive cardiac
      hypertrophy.

PMID- 8263892
TI  - Assessment of late potentials in patients with essential hypertension by the
      signal-averaged electrocardiogram with five year follow-up.
AB  - Both the Framingham and Manitoba Heart Studies have identified
      electrocardiographic left ventricular (LV) hypertrophy (LVH) as a risk factor for
      sudden cardiac death. Low amplitude ventricular late potentials in the terminal
      part of ventricular activation have been associated with sustained ventricular
      tachycardia and have identified those at risk for sudden cardiac death.
      Therefore, we prospectively examined 23 essential hypertensives without known
      symptomatic coronary heart disease by two-dimensional echocardiography and signal
      averaged electrocardiograms (SAECGs) for the detection of ventricular late
      potentials. The SAECG vector-magnitude complex measurements included the total
      duration of the complex (QRSd), the voltage in the last 40 ms (V40), and the
      duration of low amplitude signals < 40 microV in the terminal portion of the
      complex (LASd). Echocardiographic parameter means were: LV diastolic diameter =
      46.0 +/- 4.5 mm, combined septal and posterior wall thickness = 23.3 +/- 4.2 mm,
      LV mass (Woythaler method) = 235.1 +/- 69.1 g, LV mass (Penn method) = 199.5 +/-
      55.3 g and ejection fraction = 63.9 +/- 6.2%. SAECG measurement means were QRSd =
      88.2 +/- 9.9 ms, V40 = 63.1 +/- 34.7 microV RMS, and LASd = 23.5 +/- 10.0 ms. No
      echocardiographic parameter correlated with SAECG duration; however, age
      correlated with QRSd (r = 0.48, P = 0.02). Posterior wall thickness (r = -0.43, P
      = 0.04), LV mass index (r = -0.44, P = 0.03) and LV mass/height (r = -0.49, P =
      0.02) inversely correlated with LASd.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263893
TI  - Hypertension education: patient knowledge and satisfaction.
AB  - Education of patients with various diseases, including hypertension, usually
      occurs at an individual level through a patient's doctor as well as via various
      media campaigns which also includes general community education. To evaluate
      their effects, the knowledge of 84 patients with hypertension was evaluated by a
      simple 13 question true/false questionnaire and the results compared with 58
      normotensive subjects matched for sex, age and educational status. A significant
      difference in knowledge about hypertension could not be elicited between the two
      groups even when compared for sex or educational status. However, subjects > 70
      years of age (hypertensives and controls) demonstrated a lower level of knowledge
      (P < 0.05). Further questioning of the hypertensive group elicited a high level
      of satisfaction with their doctor's educational skills (68%) and 57% were
      satisfied with their own knowledge. Nevertheless, 70% requested more information
      about their disease. These results suggest a reasonable level of knowledge within
      the general community presumably reflecting community education programmes. While
      hypertensive patients were not more knowledgeable under the test conditions, they
      were reasonably satisfied with their knowledge which they stated came primarily
      from their doctor. Nevertheless, these findings question the effectiveness of
      some current patient education initiatives.

PMID- 8263894
TI  - Characterization of hypertensive subjects who become normotensive during three
      months of office BP follow-up: comparison with subjects with sustained
      hypertension and normotensives, and follow-up after two years.
AB  - After an observation period of three months, 83% of new hypertensives (n = 84),
      identified in a population survey, became normotensive. Those with sustained
      hypertension (n = 14) were compared with 14 initially hypertensives who became
      normotensive and 14 normotensives, matched for age and sex, using ambulatory and
      exercise BP and echocardiography (both M-mode and Doppler). The initially
      hypertensive group (n = 11) was re-examined after two years follow-up. The 24h
      mean ambulatory and submaximal systolic exercise BP did not differ between
      sustained (139/92 and 210 mmHg) and initially hypertensives (143/95 and 217
      mmHg), being significantly lower in the normotensive group (129/85 and 198 mmHg).
      Left ventricular mass did not differ between the initially hypertensive and the
      normotensive groups, being significantly higher in the sustained hypertensives.
      In both hypertensive groups, as compared with normotensives, the ratio between
      flow velocity in early and late diastole (E/A ratio) tended to be lower and the
      early diastolic deceleration time (DT) was significantly shorter. After two
      years, in the untreated initially hypertensives, office DBP had increased to
      hypertensive values, without change in ambulatory BP, left ventricular mass or
      early diastolic deceleration time. The E/A ratio had decreased to a level < 1. We
      conclude that the subjects who became normotensive after three months office BP
      follow-up have a BP load and signs of compromised left ventricular diastolic
      function similar to that of the sustained hypertensives, but without increased
      left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263895
TI  - Effect of value-added utilities on prescription refill compliance and health care
      expenditures for hypertension.
AB  - A randomised trial was undertaken to discern the effect of pharmacy-based value
      added utilities on prescription refill compliance with antihypertensive therapy
      and subsequent health care expenditures. The subjects were 304 Medicaid
      beneficiaries from the state of Florida, previously untreated for mild to
      moderate hypertension, prescribed 240 mg of calcium channel antagonist verapamil
      once daily and monitored regarding prescription refill compliance and health
      service utilisation for one year. Subjects provided informed consent and were
      randomly assigned to one of four experimental groups: (1) the control cohort
      received standard pharmaceutical care with each dispensing of antihypertensive
      therapy, (2) the second cohort received standard pharmaceutical care and was
      mailed a medication-refill reminder ten days prior to each sequential refill
      date, (3) the third cohort received standard pharmaceutical care and was provided
      unit-of-use packaging with each prescription-refill request and (4) the fourth
      cohort received standard pharmaceutical care, mailed medication-refill reminders
      and unit-of-use packaging. Analysis of variance (ANOVA) procedures revealed that
      patients receiving mailed prescription-refill reminders, unit-of-use packaging or
      a combination of both interventions achieved a significant (P < or = 0.05)
      increase in the Medication Possession Ratio (MPR) for antihypertensive therapy
      relative to controls. Receipt of both interventions resulted in a significant (P
      < or = 0.05) improvement in the MPR for antihypertensive therapy relative to all
      other groups no significant difference was discerned between groups receiving
      either mailed prescription-refill reminders or unit-of-use packaging.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8263896
TI  - Utility of a sustained-release formulation for antihypertensive therapy.
AB  - Recent pharmacotherapeutic advances in the treatment of hypertension have
      included the development of sustained-release (SR) dosage formulations, providing
      patients with the convenience of once daily administration. A one year
      retrospective analysis was undertaken to determine the economic utility of
      providing prescription coverage for the SR formulation of verapamil, a calcium
      channel antagonist, under the state of Florida's Medicaid programme. Data for
      this analysis were derived from the state of Florida's Medicaid computer archive.
      The study population consisted of 274 ambulatory beneficiaries diagnosed with
      hypertension and prescribed either the SR or immediate-release (IR) formulation
      of verapamil. Multivariate regression analysis was used to discern the
      incremental influence of selected demographic characteristics, utilisation of
      medical services prior to diagnosis for hypertension and prescribed formulation
      of verapamil on health care expenditures one year post-diagnosis. Patients
      prescribed the SR formulation of verapamil achieved a significant (P < or = 0.05)
      increase in the Medication Possession Ratio (MPR), an index of compliance, (0.87
      +/- 0.13) relative to patients prescribed the IR formulation (0.56 +/- 0.10).
      Results indicate that receipt of verapamil in an SR formulation was associated
      with a significant (P < or = 0.05) decrease in aggregate health care expenditures
      of $110.14 over the one year study period. Receipt of the SR formulation was
      associated with an increase in expenditures for antihypertensive therapy
      ($117.83, p < or = 0.05) and a decrease in financial commitments for physician
      ($50.42, p < or = 0.05), hospital ($153.61, p < or = 0.05) and laboratory
      ($23.94, p < or = 0.05) services.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263897
TI  - Toxicokinetics and biotransformation of pentachlorophenol in the topsmelt
      (Atherinops affinis).
AB  - The toxicokinetics and biotransformation of pentachlorophenol (PCP) were
      determined in the topsmelt (Atherinops affinis). In a static system, topsmelt (n
      = 9) were exposed to 50 micrograms/L of [U-14C]PCP for 24 hours to determine the
      absorption rate constant (Ka), the whole-body bioconcentration (at steady-state
      conditions), the elimination rate constant (Ke), and the elimination half-life
      (t1/2). Kinetics were determined by direct quantitation of radioactivity in the
      exposure water. Following exposure, fish were placed in a flow-through metabolism
      chamber for 24 hours to allow depuration of retained residues, which were
      collected on XAD-4 resin. Excreted residues were identified and quantified by
      high-pressure liquid co-chromatography, fraction collection, and liquid
      scintillation counting. The Ka and Ke, calculated using a simplified model, were
      0.012 +/- 0.005/h and 0.014 +/- 0.003/h, respectively, while the 24 hour total
      concentration factor was 278.0 +/- 182.0 and the t1/2 was 52.7 +/- 11.2. During
      24 hours of exposure to clean seawater, topsmelt depurated 32.9% of retained
      residues, and while PCP was primarily excreted unchanged (64.9%), significant
      amounts of both pentachlorophenylsulfate (18.9%) and pentachloro-beta-D
      glucuronide (16.2%) were also formed.

PMID- 8263898
TI  - The effect of mainstream and sidestream cigarette smoke exposure on oxygen
      defense mechanisms of guinea pig erythrocytes.
AB  - We have studied the effects of short-term exposure of guinea pigs to cigarette
      smoke under both mainstream (MS) and sidestream (SS) conditions on the activities
      of major antioxidant enzymes and lipid peroxidation potential of erythrocytes.
      The smoke-exposed groups had an increase in the activity of superoxide dismutase
      (SOD), a decrease in the activities of glutathione peroxidase (GSH-Px) and NADPH
      generating enzymes, and no change in the activity of catalase. Furthermore, there
      was a significant increase in the in vitro lipid peroxidation potential of
      erythrocytes in both MS- and SS-exposed groups. However, the lipid peroxidation
      potential was higher in the MS-exposed group than that in the SS-exposed group.

PMID- 8263899
TI  - Inhibition of insulin production by cyproheptadine in RINm5F rat insulinoma
      cells.
AB  - The clonal insulin producing cell line RINm5F was evaluated as a model for the
      action of cyproheptadine (CPH)-like diabetogenic compounds in the rat pancreas.
      Treatment with 10 microM CPH and selected structural analogs under culture
      conditions produced a progressive loss of cellular insulin which reached 30% of
      control within 24 hours. Comparison of the activities of the analogs 4
      diphenylmethylpiperidine (4-DPMP) and 2-diphenylmethylpiperidine (2-DPMP) to
      produce cellular insulin depletion showed that 4-DPMP was as active as CPH but 2
      DPMP had no activity at the highest concentration employed (10 microM). The CPH
      metabolite desmethyl CPH-epoxide was five times more active than the parent
      compound in producing loss of insulin in RINm5F cells. These results are
      consistent with previously published results of CPH actions in vivo. An
      inhibition of insulin biosynthesis with no loss of preproinsulin mRNA occurred in
      RINm5F cells treated with CPH or DMCPH-epoxide. This suggests that an effect on
      transcription may not be the primary action by which CPH and its analogs inhibit
      insulin synthesis in vivo.

PMID- 8263900
TI  - Characterization of cytochromes P450 in liver and kidney of rats treated with di
      (2-ethylhexyl)phthalate.
AB  - A polyclonal antibody was made to a liver cytochrome P450 purified from di-(2
      ethyl-hexyl)phthalate (DEHP)-treated Sprague-Dawley rats and was used to identify
      the CYP4A forms in liver and kidney cortex microsomes of control rats and rats
      treated with this peroxisome proliferator. Three clearly separated major protein
      bands were recognized on western blots in liver microsomes of control male rats
      or male rats treated with a single dose of DEHP, which, based on the description
      of relative mobility, tissue specificity, and sex dependent expression of CYP4A
      forms (Sundseth and Waxman (1992). J. Biol. Chem., 267, 801-810), correspond to
      the migration pattern of forms 4A1, 4A2, and 4A3 in clofibrate-treated rats. The
      administration of DEHP for 2 or 3 days caused a loss of resolution of two of the
      protein bands. The protein band corresponding to 4A2 was absent in liver or
      kidney cortex microsomes of DEHP-treated or control female rats and was not
      always visible in the livers of control male rats. The purified P450DEHP
      supported the hydroxylation of arachidonic acid at both the 19- and 20-carbon
      atoms with turnover rates of 1.4 +/- 0.2 and 22.7 +/- 2.5 nmoles per minute per
      nmol P450, respectively. No measurable amounts of hydroxylated products were
      obtained when prostaglandin E1, leukotriene B4, or testosterone were used as
      substrates. Another member of the CYP4 family, 4B1 from rabbit lung microsomes,
      was also recognized by this antibody on western blot analysis; however, rabbit
      lung form 4A4 showed only minimal cross-reactivity with this antibody.

PMID- 8263901
TI  - Substrate specificity of rat liver aldehyde dehydrogenase with
      chloroacetaldehydes.
AB  - Chlorinated acetaldehydes have been the focus of research due to their role as
      reactive intermediates and their possible occurrence in chlorinated drinking
      water. This study investigated the in vitro substrate specificity of cytosolic
      and mitochondrial rat liver aldehyde dehydrogenase toward these compounds.
      Monochloroacetaldehyde was found to be extensively metabolized by these enzymes,
      to an even greater extent than the standard substrate propionaldehyde.
      Dichloroacetaldehyde was metabolized to a much lesser extent, and chloral hydrate
      is not metabolized by this enzyme family. The Km (mM) and Vmax (Vmax for
      propionaldehyde set to 100) values with the low Km cytosolic enzyme were
      monochloroacetaldehyde 0.046 and 582, and dichloroacetaldehyde 0.13 and 54.9, and
      those with the high Km cytosolic enzyme were dichloroacetaldehyde 0.35 and 23.4.
      The values with the low Km mitochondrial enzyme were monochloroacetaldehyde 0.057
      and 462 and dichloroacetaldehyde 0.038 and 12.9, and those with the high Km
      mitochondrial enzyme were monocloroacetaldehyde 0.024 and 55.5 and
      dichloroacetaldehyde 0.29 and 3.44. These data suggest that aldehyde
      dehydrogenase plays a significant role in the metabolism of
      monochloroacetaldehyde and, to some extent, dichloroacetaldehyde. Some evidence
      also suggested that alcohol dehydrogenase plays a significant role in the
      metabolism of dichloroacetaldehyde and chloral hydrate.

PMID- 8263902
TI  - Purification and properties of a diisopropyl-fluorophosphatase from squid
      Todarodes pacificus steenstrup.
AB  - A diisopropyl-fluorophosphatase (DFPase) was purified from brain and ganglia of
      squid Todarodes pacificus steenstrup. The DFPase had a preference in hydrolysis
      toward diisopropylphosphorofluoridate (DFP). It also was able to hydrolyze O
      1,2,2-trimethylpropyl methylphosphofluoridate (soman) and O-isopropyl
      methylphosphonofluoridate (sarin) at nearly equal hydrolytic rates but only 1/10
      that of DFP. The hydrolytic activity toward diethyl-p-nitrophenylphosphate
      (paraoxon) was very low compared with DFP, soman, and sarin. The DFPase was
      purified 330-fold to a specific activity of 18,300 n mol/min/mg protein. Its
      molecular weight was 34,000 dalton determined by gel-filtration chromatography.
      Mn2+ stimulation of the DFPase was not observed when DFP and soman were the
      substrates, but with sarin, the rate increased onefold in the presence of 1.0 mM
      of Mn2+. Ethylenediamine tetraacetic acid disodium (EDTA-Na2) at 0.05 M inhibited
      the DFPase activity about 30%. It could be concluded that this DFPase belongs to
      the squid-type DFPase.

PMID- 8263903
TI  - An electronic cryoprobe for cryosurgery using heat pipes and thermoelectric
      coolers: a preliminary report.
AB  - A hand-held fully electrically powered and programmable cryoprobe for general
      purpose cryosurgery and cryotherapy has been developed. By combining the
      technologies of thermoelectric cooling and heat pipes, the temperature at the tip
      of the probe can easily reach -50 to -60 degrees C. It can hold below -40 degrees
      C when it cools a load of 10 W at the tip. Previous efforts developing cryoprobes
      made of thermoelectric modules have been hindered by the inherent characteristics
      of commercially available thermoelectric coolers: low efficiency, size and
      inflexible shape and very sensitive to heat intensity and thermal insulation.
      Matching thermoelectrics with heat pipes uses the advantages of both
      technologies. In the cryoprobe the heat pipe is used to focus and transport the
      cooling power of multi-thermoelectric modules. The heat flux for the
      thermoelectric modules is reduced and their efficiencies are increased. The
      transport of heat by a heat pipe also allows flexible access to treated spots of
      patients.

PMID- 8263904
TI  - A new device producing ambulatory intermittent pneumatic compression suitable for
      the treatment of lower limb oedema: a preliminary report.
AB  - The ideal conservative treatment for lower limb oedema would be one that provided
      intermittent compression whilst allowing the patient to remain mobile. In this
      article we describe the development of a pneumatic ambulatory compression device
      that utilizes the patient's weight applied, during walking, to air cells under
      the foot to provide compression to the ankle and calf. In volunteer studies this
      device typically produced a cycle of interface pressure changes from 20 to 45-50
      mmHg on the lower calf and 20 to 35-40 mmHg on the upper calf.

PMID- 8263905
TI  - Clinical applications of electrical impedance tomography.
AB  - This article is a preliminary review of the possible clinical applications of
      electrical impedance tomography (EIT). The applications to, for example, the
      central nervous, respiratory, cardiovascular and digestive systems are covered.
      It is concluded that the area of greatest potential application of EIT is
      monitoring cardiopulmonary function, but that studies on much larger groups of
      patients than have been carried out hitherto are required to fully assess the
      potential of EIT as a clinical tool.

PMID- 8263906
TI  - Bladder volume estimation in the elderly using a portable ultrasound-based
      measurement device.
AB  - We assessed the accuracy and ease of use of the BladderScan (BVI 2000) portable
      ultrasound-based bladder volume measurement device in a geriatric outpatient
      population. The Geriatric Continence Clinic nurse and physician each made 73
      measurements on 36 subjects. Although the correlation coefficients between the
      true and ultrasound measurements were highly significant the mean differences
      were significantly different from zero. We suggest that, rather than considering
      the correlation coefficient, the accuracy required of the device should be
      described by a function of estimated versus true bladder volume. This function
      should vary depending on each particular decision-making process in which the
      estimate of volume is to be used. This instrument automatically estimates bladder
      volume once the user has completed the image creation and selection part of the
      process. The users in this study had difficulties with this imaging process.
      Possible ways in which the device's automated signal processing and volume
      calculation algorithms could be improved became evident during this study and are
      discussed.

PMID- 8263908
TI  - Certified rural health clinics increase available health care.

PMID- 8263907
TI  - Case records of the Department of Medicine University of Mississippi Medical
      Center. Moderately differentiated adenocarcinoma of the colon with extension
      through the musculature into the pericolonic fat and metastasis to one of six
      lymph nodes and the liver.

PMID- 8263909
TI  - "Details, details".

PMID- 8263910
TI  - Ribosomal proteins L11 and L10.(L12)4 and the antibiotic thiostrepton interact
      with overlapping regions of the 23 S rRNA backbone in the ribosomal GTPase
      centre.
AB  - The Escherichia coli ribosomal protein (r-protein) L11 and its binding site on 23
      S ribosomal RNA (rRNA) are associated with ribosomal hydrolysis of guanosine 5'
      triphosphate (GTP). We have used hydroxyl radical footprinting to map the
      contacts between L11 and the backbone riboses in 23 S rRNA, and to investigate
      how this interaction is influenced by other ribosomal components. Complexes were
      characterized in both naked 23 S rRNA and ribosomes from an E. coli L11-minus
      strain, before and after reconstitution with L11. The protein protects 17 riboses
      between positions 1058 and 1085 in the naked 23 S rRNA. Within the ribosome, L11
      also interacts with this rRNA region, although the protection effects are subtly
      different and extend to nucleotide 1098. The pentameric r-protein complex
      L10.(L12)4 binds to an adjacent site on the rRNA, protecting riboses at positions
      1043, 1046 to 1049, 1053 to 1055 and increasing the accessibility of position
      1068. The overlap in the positions affected by r-proteins L11 and L10.(L12)4, and
      the increase in protection between positions 1078 and 1084 when they are bound at
      the same time, reflect the mutually cooperative nature of their interaction with
      the rRNA. The data support a model for the tertiary configuration of the rRNA
      region, in which two stem-loop structures fold so that the loops lie in close
      proximity, with the main ribose interactions of L11 within the minor groove of
      one of the stems. The conformation of the rRNA-L11 interaction is modulated by
      L10.(L12)4 and other proteins within the ribosome. The antibiotics thiostrepton
      and micrococcin inhibit the catalytic functions of this region by slotting in
      between the accessible loops and interacting with nucleotides there.

PMID- 8263911
TI  - A novel arrangement of zinc-binding residues and secondary structure in the C3HC4
      motif of an alpha herpes virus protein family.
AB  - A highly conserved, cysteine-rich region plays a crucial role in the function of
      a family of regulatory proteins encoded by alpha herpes viruses. The so-called
      C3HC4 motif spans approximately 60 residues and has been predicted to bind zinc.
      This motif occurs in a number of other viral and cellular proteins, many of which
      appear to be involved in some aspect of the regulation of gene expression. We
      have cloned and expressed in bacteria a portion of immediate-early protein Vmw110
      of herpes simplex virus type 1 that encompasses the C3HC4 motif, and the
      equivalent regions from the homologous proteins of varicella zoster virus and
      equine herpes virus type 1 (EHV-1). All three polypeptides were purified and
      found to bind zinc stably. None of the three interacted significantly with either
      DNA or RNA under our assay conditions. The EHV-1 domain yielded interpretable
      proton nuclear magnetic resonance spectra. Assignment of resonances and analysis
      of nuclear Overhauser effects revealed its secondary structure. Starting from the
      N terminus, this consists of an ordered but irregular loop, the first two strands
      of a triple-stranded antiparallel beta-sheet, two turns of an alpha-helix, a
      second irregular loop, and the third strand of the beta-sheet. It appears that,
      taking the cysteine and histidine residues in turn, cysteine residues I, II, IV
      and V co-ordinate one zinc atom while the histidine residue and cysteine residues
      III, VI and VII co-ordinate a second zinc atom. This arrangement of secondary
      structure differs from that found in other characterized zinc-containing
      proteins.

PMID- 8263912
TI  - The structures of native phosphorylated chicken cystatin and of a recombinant
      unphosphorylated variant in solution.
AB  - The solution structures of the phosphorylated form of native chicken cystatin and
      the recombinant variant AEF-S1M-M29I-M89L were determined by 2D, 3D and 4D-NMR.
      The structures turn out to be very similar, despite the substitutions and the
      phosphorylation of the wild-type. Their dominant feature is a five-stranded beta
      sheet, which is wrapped around a five-turn alpha-helix, as shown by X-ray
      crystallographic studies of wild-type chicken cystatin. However, the NMR analysis
      shows that the second helix observed in the crystal is not present in solution.
      The phosphorylation occurs at S80, which is located in a flexible region. For
      this reason, very few effects on the structure are observed. Comparison of
      structures of the unphosphorylated variant and the wild-type shows small effects
      on H84 which is located in the supposed recognition site of the serine kinase.
      This recognition site appears to be well structured as a large loop-containing
      bulge of the beta-sheet. The N termini of both mutants, which contribute to a
      large extent to the binding to the proteinase, are very flexible. A loop
      structure involving the residues L7 to A10 as found in related inhibitors, such
      as in the kininogen domains 2 and 3, is not sufficiently populated to be
      observed.

PMID- 8263913
TI  - Conformational variability of chicken cystatin. Comparison of structures
      determined by X-ray diffraction and NMR spectroscopy.
AB  - The structural model derived from X-ray crystallography for unphosphorylated wild
      type chicken cystatin is compared with two chicken cystatin structures derived
      from NMR spectroscopy: the phosphorylated wild-type and the genetically
      engineered variant AEF-SIM-M29I-M89L. The comparison shows the same overall fold,
      but also significant differences in structurally variable segments of the
      polypeptide chain. The largest such segment, comprising residues 71 to 89, is a
      region characteristic of the family 2 cystatin inhibitors which contains a
      disulphide bridge (71-81) and the phosphorylation site (Ser80) discussed in the
      accompanying article. In the crystal structure, the segment 71 to 76 is found as
      a flexible loop, 77 to 85 as an alpha-helical segment, and 86 to 89 is completely
      undefined. The solution NMR structures on the other hand are disordered in the
      initial segment 72 to 80, have an extended conformation at 81 to 83 in contact
      with the beta-sheet, and clearly show a beta-turn at residues 87 to 90. The
      segment comprising residues 53 to 57, with smaller variability, is of particular
      interest as the hairpin loop conserved throughout the cystatin superfamily which
      binds to the cysteine proteinase. In most of the solution NMR structures, this
      segment adopts a conformation more like that of stefin B, a family 1 cystatin
      inhibitor, as was observed in the crystal structure of its inhibitory complex
      with papain. The differences between the structures are rationalized by an
      examination of the crystal contacts generated by hypothetical crystal packing of
      the NMR structures. Additionally, the X-ray refinement shows evidence of
      conformational disorder in the crystal. Joint refinement with NOE restraints and
      reflection data does not produce a structure to satisfy the restraints of both
      methods.

PMID- 8263914
TI  - Model studies relating nuclear magnetic resonance data with the three-dimensional
      structure of protein-DNA complexes.

PMID- 8263915
TI  - Detailed analysis of the free and bound conformations of an antibody. X-ray
      structures of Fab 17/9 and three different Fab-peptide complexes.
AB  - A new orthorhombic crystal form of Fab 17/9 has been determined in complex with a
      7-mer peptide from influenza virus hemagglutinin (HA1 101-107, acetylated and
      amidated). The three-dimensional structure was resolved to 2.8 A with an improved
      refinement and better geometry than two previously determined Fab 17/9-peptide
      (HA1 100-108) complexes, facilitating a detailed description of the Fab-peptide
      interactions. The binding pockets and the peptide antigen are structurally
      similar in all three peptide complexes of Fab 17/9. The peptide adopts an
      extended conformation (residues 100 to 103) and a type I reverse turn (residues
      104 to 107). Additionally, the antigenic determinant described here correlates
      well with previous epitope mapping studies. The structures of the free and
      antigen bound Fab illustrate the role of induced fit as a mechanism for antibody
      antigen recognition. Fab 17/9 undergoes a large conformational change, mainly in
      the H3 loop, upon peptide binding. As a result, the shape of the binding pocket
      changes substantially in the liganded Fab. However, the backbone conformations of
      the other hypervariable loops (L2, L3, H1 and H2) show no significant difference
      between free and bound structures. The conformation of the L1 loop is also
      maintained in all structures, but its position relative to the framework varies
      in different crystal environments. The availability of three X-ray structures of
      an Fab-peptide complex in three different space groups makes it possible to
      clearly distinguish between crystal packing and antigen binding as the cause of
      structural differences. Two distinct H3-loop conformations, free and bound, are
      observed with no evidence otherwise for multiple conformations of the
      hypervariable loops (CDRs) or increased flexibility in either the free or bound
      forms.

PMID- 8263916
TI  - X-ray structure of a monomeric cyclophilin A-cyclosporin A crystal complex at 2.1
      A resolution.
AB  - The crystal structure of a complex between recombinant human cyclophilin A (Cyp)
      and cyclosporin A (CsA) has been determined from a novel orthorhombic crystal
      form that contains only one monomer of complex per asymmetric unit rather than
      five in the previously determined tetragonal structure. The structure has been
      refined at 2.1 A resolution to a crystallographic R-factor of 16.7%. The
      conformation of Cyp is practically unchanged with respect to the tetragonal form.
      A certain number of previously undefined side-chains have been located in the
      electron density and a very detailed picture of the ordered solvent structure has
      been obtained. The interactions between CsA and Cyp are conserved. A network of
      the possibly conserved, water-mediated contacts is described. The structure of
      CsA in the monomeric complex is similar to that of the decameric complex, but
      shows a few small differences in the so-called effector domain of CsA, probably
      due to differences in crystal environment. The fact that this monomeric crystal
      form can be obtained shows that the formation of pentamer or decamer complexes is
      not a generally observed phenomenon and is not a prerequisite for biological
      activity.

PMID- 8263917
TI  - Conformational flexibility in glutamate dehydrogenase. Role of water in substrate
      recognition and catalysis.
AB  - We have solved the structure of the binary complex of the glutamate dehydrogenase
      from Clostridium symbiosum with glutamate to 1.9 A resolution. In this complex,
      the glutamate side-chain lies in a pocket on the enzyme surface and a key
      determinant of the enzymic specificity is an interaction of the substrate gamma
      carboxyl group with the amino group of Lys89. In the apo-enzyme, Lys113 from the
      catalytic domain forms an important hydrogen bond to Asn373, in the NAD(+)
      binding domain. On glutamate binding, the side-chain of this lysine undergoes a
      significant movement in order to optimize its hydrogen bonding to the alpha
      carboxyl group of the substrate. Despite this shift, the interaction between
      Lys113 and Asn373 is maintained by a large-scale conformational change that
      closes the cleft between the two domains. Modelling studies indicate that in this
      "closed" conformation the C-4 of the nicotinamide ring and the alpha-carbon atom
      of the amino acid substrate are poised for efficient hydride transfer.
      Examination of the structure has led to a proposal for the catalytic activity of
      the enzyme, which involves Asp165 as a general base, and an enzyme-bound water
      molecule, hydrogen-bonded to an uncharged lysine residue, Lys125, as an attacking
      nucleophile in the reaction.

PMID- 8263918
TI  - Contribution of buried hydrogen bonds to protein stability. The crystal
      structures of two barnase mutants.
AB  - The crystal structures of two barnase mutants, Tyr78-->Phe and Ser91-->Ala, have
      been determined to 2.2 A resolution. In both cases, a buried hydroxyl group that
      makes two hydrogen bonds within the protein was replaced by a hydrogen atom. It
      is found that neither mutation causes any structural changes, within the limits
      of error, compared with wild-type and so are confirmed to be non-disruptive.
      Solvent molecules are not observed in the cavities created by removal of the
      respective hydroxyl groups and no new interactions are introduced. The local
      water structure surrounding both sites of mutation is well conserved and
      resembles that of the wild-type. All four water molecules making contacts with
      the side-chain of residue 78 and two water molecules nearest to residue 91 in the
      wild-type are found within a sphere of 0.5 A radius, at the equivalent positions
      of the respective mutant. No new water molecules are found bound to any of the
      hydrogen bond donor or acceptor residues involved in these two mutation sites.
      Previous protein engineering experiments established that the solvent
      inaccessible phenolic OH of Tyr78 that makes hydrogen bonds with two uncharged
      groups (main-chain NH and CO) contributes 1.4 kcal mol-1 to protein stability,
      while the solvent-inaccessible OH of Ser91 that makes hydrogen bonds with an
      uncharged main-chain NH and a charged group (O gamma 1) contributes 1.9 kcal mol
      1. These stability measurements can now be attributed primarily to the loss of
      the hydrogen bonding interactions because both mutations neither disrupt the
      respective protein and local solvent structures, upset the overall hydrogen
      bonding pattern nor introduce new interactions. The mutations Tyr78-->Phe and
      Ser91-->Ala are thus good examples of "non-disruptive deletions" and the results
      of mutagenesis can be analysed at the simplest level.

PMID- 8263919
TI  - Solution structure of a parallel-stranded G-quadruplex DNA.
AB  - This paper reports on the solution structure of a parallel-stranded G-quadruplex
      formed by the Tetrahymena telomeric sequence d(T-T-G-G-G-G-T) whose NMR
      parameters in potassium cation containing solution were previously published from
      our laboratory. The structure was determined by combining a quantitative analysis
      of the NMR data with molecular dynamics calculations including relaxation matrix
      refinement. The combined NMR-computational approach yielded a set of seven
      distance-refined structures with pairwise RMSDs ranging from 0.66 to 1.30 A for
      the central G-G-G-G tetranucleotide segment. Four of the seven structures were
      refined further using complete relaxation-matrix calculations to yield solution
      structures with pairwise RMSDs ranging from 0.64 to 1.04 A for the same
      tetranucleotide segment. The R-factors also decreased on proceeding from the
      distance-refined to relaxation matrix-refined structures. The four strands of the
      G-quadruplex are aligned in parallel and are related by a 4-fold symmetry axis
      coincident with the helix axis. Individual guanines from each strand form planar
      G.G.G.G tetrad arrangements with each tetrad stabilized by eight hydrogen bonds
      involving the Watson-Crick and Hoogsteen edges of the guanine bases. All guanines
      adopt anti glycosidic torsion angles and S type sugar puckers in this right
      handed parallel-stranded G-quadruplex structure. The four G.G.G.G tetrad planes
      stack on each other with minimal overlap of adjacent guanine base planes within
      individual strands. The thymine residues are under-defined in the solution
      structure of the d(T-T-G-G-G-G-T) G-quadruplex and sample amongst multiple
      conformations in solution.

PMID- 8263920
TI  - The free energy, enthalpy and entropy of native and of partially denatured closed
      circular DNA.
AB  - We have used gel electrophoresis to measure the progress of local denaturation in
      closed circular pBR322 DNA as a function of temperature and linking deficiency,
      delta Lk. Local denaturation is closely coupled to supercoiling in closed DNA,
      requiring statistical mechanical methods for analysis. We have applied these
      methods to the experimental data to evaluate the free energies for three
      associated molecular processes. These processes are changes in the residual
      linking deficiency, delta Lkr, initiation of local denaturation, and twisting of
      denatured strands about one another. Our results confirm the quadratic dependence
      of the supercoiling free energy upon delta Lk, with a free energy coefficient of
      740/N kcal/mol at 37 degrees C, where N is the number of base-pairs. The free
      energy of initiation of denaturation is 10.2(+/- 0.7) kcal/mol. The free energy
      of interstrand twisting of denatured regions varies with the square of the twist
      density, with proportionality coefficient C tau = 1.62 (+/- 0.11) kcal/rad2 at 37
      degrees C. We have also calculated the entropy and enthalpy of these three
      processes, using the temperature dependence of the respective free energies. We
      find that both the entropy and the enthalpy of supercoiling are positive and vary
      quadratically with delta Lk. The free energy of initiation of denaturation is
      independent of temperature, hence arises primarily from a change in enthalpy. The
      entropy and enthalpy of interstrand twisting of denatured regions are both
      positive, and the twisting force constant decreases with temperature. These
      results differ considerably from expectations based solely upon considerations of
      chain configuration in vacuo, indicating the importance of solvent-dependent
      factors in determining the structure of closed circular DNA.

PMID- 8263921
TI  - Further examination of the intermediate state in the denaturation of the
      tryptophan synthase alpha subunit. Evidence that the equilibrium denaturation
      intermediate is a molten globule.
AB  - To further characterize the intermediate state in the denaturation of tryptophan
      synthase alpha subunit from Escherichia coli, we have carried out differential
      scanning calorimetry in various concentrations of urea near pH 8.5. The heat
      capacity curve of the intermediate has no excess heat capacity nor any
      transition. This indicates that the intermediate is a thermodynamically denatured
      form. Although the intermediate retains significant CD signal in the far-uv
      region, the tertiary structure of the intermediate is disrupted as judged by the
      near-uv CD spectra and 1H NMR spectra in the aromatic region. This intermediate
      might be similar to a molten globule state. These results do not support our
      earlier proposal that the intermediate of the alpha subunit in the denaturation
      process retains an intact N-terminal domain, but that the C-terminal domain
      unfolds.

PMID- 8263922
TI  - Role of an active site residue analyzed by combination of mutagenesis and
      coenzyme analog.
AB  - Asp222 of aspartate aminotransferase is an active-site residue which interacts
      with the pyridine nitrogen of the coenzyme, pyridoxal 5'-phosphate (PLP). The
      roles of Asp222 in the catalytic mechanism of Escherichia coli aspartate
      aminotransferase have previously been explored by site-directed mutagenesis.
      These studies confirmed that a negatively charged residue at position 222 is
      essential for catalysis, but the reason for this remained speculative. In the
      present studies, the roles of Asp222 were clarified experimentally by analyzing
      the mutant D222A enzyme (Asp222 replaced by Ala) reconstituted with the coenzyme
      analog N(1)-methylated PLP (N-MePLP). Spectroscopic and kinetic analyses showed
      that Asp222 stabilizes the protonated N(1) of PLP, raising the pKa value of N(1)
      by more than five units, in the active site of AspAT. The positive charge at N(1)
      accelerates abstraction of the alpha-proton from the amino acid substrate,
      stabilizing the transition state by 1.4 to 4.5 kcal.mol-1 in the reaction with
      aspartate. X-ray crystallographic (2.0 A resolution) and CD spectroscopic studies
      suggest that the coenzyme analog is not held in a proper orientation within the
      active site of D222A (N-MePLP). This may account for the finding that the
      catalytic activity was recovered only partially by the reconstitution of D222A
      with N-MePLP. These results fully support the following postulated role of
      Asp222: the negative charge of Asp222 stabilizes the positive charge at N(1) of
      PLP and thereby enhances the function of PLP as an electron sink.

PMID- 8263923
TI  - Crystal structure of Myxococcus xanthus nucleoside diphosphate kinase and its
      interaction with a nucleotide substrate at 2.0 A resolution.
AB  - The X-ray crystallographic structure of nucleoside diphosphate (NDP) kinase from
      Myxococcus xanthus has been determined using multiple isomorphous replacement
      techniques and refined at 2.0 A resolution to a crystallographic R-factor of
      0.17. This is the first report of the structure of an enzymatically active NDP
      kinase and of the enzyme with a bound nucleotide. The structure has been
      determined in P4(3)2(1)2 and I222 crystal forms. The enzyme monomer consists of a
      four-stranded antiparallel beta-sheet. The surfaces of the sheet are partially
      covered with five helical segments. There are two protein molecules in the
      asymmetric unit of the tetragonal crystal form. They form a dimer with an
      extensive interface in which 1092 A2 per monomer is buried. The majority of the
      contact area in the dimer interface is between hydrophobic or aromatic residues.
      Two dimers are related by a crystallographic 2-fold axis to yield a tetramer.
      This tetramer is also present in the orthorhombic crystals; however, in this
      case, the 222 symmetry is entirely crystallographic. Upon tetramer formation, an
      additional 473 A2 of solvent-accessible surface area from each monomer becomes
      buried. The interface between dimers in the tetramer is stabilized by salt
      bridges. Equilibrium sedimentation studies are consistent with the enzyme being a
      tetramer in solution. The structure of a complex of adenosine diphosphate (ADP)
      with the enzyme was determined and reveals that most of the nucleotide
      interactions with the protein are with the pyrophosphate and ribose groups, while
      the base has no hydrogen bonds with the protein and interacts only by stacking
      with the side chain of Phe59. The Mg2+ interacts with the pyrophosphate of the
      ADP and via a solvent molecule with the side chain of the conserved Asp120
      residue. The mode of interaction with the nucleotide is novel, with the
      nucleotide binding at the side of the beta-sheet. The structures of the
      nucleotide in crystals grown in the presence or absence of Mg2+ are essentially
      identical. In addition, the phosphotransfer reaction from adenosine triphosphate
      (ATP) to the enzyme can occur without Mg2+. This suggests that only the second
      step of the reaction in which the enzyme transfers the phosphate to a nucleoside
      diphosphate acceptor is significantly catalyzed by the metal.

PMID- 8263924
TI  - Crystallization and preliminary X-ray studies of L-aspartase from Escherichia
      coli.
AB  - Single crystals of L-aspartate ammonia-lyase (L-aspartase) from Escherichia coli
      have been obtained by microdialysis at room temperature using polyethylene glycol
      3350 and sodium acetate as co-precipitants. The crystals exhibit the symmetry of
      space group P2(1)2(1)2 with a = 156.5 A, b = 147.6 A, c = 102.5 A and diffract at
      least to 2.8 A.

PMID- 8263925
TI  - Preliminary crystallization and X-ray analysis of orthorhombic human endothelin.
AB  - Human endothelin (ET-1) is a highly potent, ubiquitous, endogenous 21 amino acid
      residue polypeptide, which acts as a vaso- and bronchoconstrictor. Crystals of
      the active, uncomplexed form of ET-1 have been grown from aqueous solutions.
      These crystals, which are long hexagonal prisms, diffract to 2.98 A and are
      apparently of the space group P222(1) with cell dimensions a = 33.5 A, b = 57.9
      A, c = 59.6 A. The six molecules in the asymmetric unit are related by non
      crystallographic symmetry operations, which result in a pseudo 6(1) appearance to
      the data.

PMID- 8263926
TI  - Crystallization and preliminary X-ray diffraction analysis of two conformations
      of intact human antithrombin.
AB  - Human antithrombin has been crystallized by microdialysis at pH 6.7 using 18%
      (w/v) polyethylene glycol-4000 as precipitant. Under these conditions two crystal
      forms grew. The first started growing after ten days, diffracted to 3.0 A
      resolution and belongs to the monoclinic space group P2(1) with two molecules in
      the asymmetric unit and unit cell dimensions a = 70.1 A, b = 101.5 A, c = 90.5 A
      and beta = 105.9 A. The other crystal form took more than three months to appear,
      diffracted to 5.5 A and belongs to the hexagonal space group of either P6(1) or
      P6(5) with unit cell dimensions of a = b = 99.3 A and c = 152.9 A and two
      molecules in the asymmetric unit. The antithrombin redissolved from the
      monoclinic crystals was shown both by SDS-polyacrylamide gel electrophoresis and
      by protein sequence analysis to be intact while that from the hexagonal crystals
      was cleaved in the reactive centre loop between the P'2 and P'3 (i.e. Leu-Asn)
      residues. Further analysis of the intact inhibitor from the monoclinic crystals
      indicated that the antithrombin was present in two different conformations; an
      active form which could inhibit thrombin and form a stable complex with the
      protease, and a form which was inactive as an inhibitor and which also did not
      act as a substrate for thrombin. This latter form also had a low affinity for
      heparin and in these ways resembles latent antithrombin. The active material from
      the monoclinic crystals had an association rate constant with thrombin in the
      presence of heparin (kass) of 7.5 x 10(7) M-1 s-1 (kass for native antithrombin =
      8.2 (+/- 1.0) x 10(7) M-1 s-1) indicating it still had effective heparin cofactor
      activity. X-ray diffraction analysis also suggests that two different protein
      conformations exist within the monoclinic crystals. Whereas the rotation function
      peak heights are equal for both molecules in the asymmetric unit using the
      structure of intact ovalbumin as a search model, one of the two molecules gives a
      much clearer signal than the other when the structures of the two cleaved
      serpins, alpha 1-antitrypsin and alpha 1-antichymotrypsin are used.

PMID- 8263927
TI  - Crystallization and preliminary X-ray analysis of human tissue factor
      extracellular domain.
AB  - The extracellular domain (residues 1 to 220) of human tissue factor has been
      cloned and expressed in Escherichia coli and purified to isoelectric homogeneity.
      Single crystals suitable for X-ray analysis have been obtained by vapour
      diffusion. They belong to the tetragonal space group P4(1)2(1)2 or P4(3)2(1)2
      with a = b = 45.2 A, c = 231.5 A, contain one molecule per asymmetric unit and
      diffract to 2.6 A resolution. Native and derivative data sets have been collected
      to 3.6 and 3.9 A, respectively.

PMID- 8263928
TI  - Crystallization of inhibited aspartic proteinase from Candida albicans.
AB  - A major secreted aspartic proteinase from Candida albicans has been crystallized
      in the presence of inhibitors to prevent autodegradation. With pepstatin a
      cleaved form of the enzyme was nevertheless found in the crystals whereas with
      the inhibitor A70450 the enzyme remained intact. The crystals containing
      pepstatin were not suitable for X-ray data collection while the crystals
      containing A70450 grew by vapour diffusion as tetragonal bipyramids, space group
      P4(3)2(1)2 (or P4(1)2(1)2), a = b = 76.2 A, c = 126.1 A, with one molecule in the
      asymmetric unit and they diffract to beyond 2.2 A.

PMID- 8263929
TI  - Crystallization of the NADP(+)-dependent glutamate dehydrogenase from Escherichia
      coli.
AB  - The NADP(+)-dependent hexameric glutamate dehydrogenase from Escherichia coli has
      been crystallized as the apo-enzyme and also in the presence of its substrates 2
      oxoglutarate, glutamate or NADP+, using either pulsed equilibrium microdialysis,
      or the hanging drop method of vapour diffusion. Three non-isomorphous, but
      related, crystal forms have been obtained, all of which belong to the
      orthorhombic system and are most likely to be in space group P2(1)2(1)2(1). One
      crystal form is grown from ammonium sulphate, includes the apoenzyme and the
      binary complexes with 2-oxoglutarate or NADP+, and has cell dimensions a = 157.5
      A, b = 212.5 A, c = 101.0 A with a hexamer in the asymmetric unit.
      Crystallizations using glutamate as the precipitant produced two further crystal
      forms, which show significant changes in the b and c cell dimensions with respect
      to the apo-enzyme crystals, with parameters a = 160.0 A, b = 217.5 A c = 92.4 A
      and a = 160.0 A, b = 223.0 A c = 92.4 A, respectively. X-ray diffraction
      photographs taken with synchrotron radiation show measurable reflections to
      beyond 3.0 A resolution.

PMID- 8263930
TI  - Crystallization and X-ray analysis of a multienzyme complex containing RUBISCO
      and RuBP.
AB  - Single crystals of a multienzyme complex isolated from spinach leaves, and
      containing RUBISCO bound to the substrate RuBP have been grown and characterized.
      The crystals belong to the orthorhombic space group P2(1)2(1)2 with a = 173 A, b
      = 134 A and c = 112 A, and contain two enzyme complex molecules in the unit cell.
      Diffraction data to 2.5 A resolution have been collected on the sychrotron source
      at the photon factory in Japan. Initial structure determination has been carried
      out using the molecular replacement method. The RUBISCO molecule in the complex
      has the normal L8S8 subunit configuration, and difference electron density is
      clearly observed for the other component enzymes and the RuBP substrate.

PMID- 8263931
TI  - Crystallization of the ribosome inactivating protein ML1 from Viscum album
      (mistletoe) complexed with beta-D-galactose.
AB  - A ribosome inactivating protein (ML1) from the mistletoe plant (Viscum album) has
      been crystallized. The crystals, grown in the presence of beta-D-galactose, are
      hexagonal, space group P6(1)22 or P6(5)22, a = b = 111.0 A, c = 309.3 A with 24
      molecules per unit cell (assuming 33% solvent by weight). The protein of
      molecular mass 63 kDa is a heterodimer consisting of two chains, A and B, joined
      by a disulfide bond. The A-chain, 29 kDa, inhibits protein synthesis by
      depurinating an adenine residue (A4324) in a highly conserved RNA loop of the 28
      S ribosomal subunit. The toxicity of the protein is mediated by the B-chain, 34
      kDa, which has lectin activity, interacting with sugar residues of glycoproteins
      and glycolipids on the surface of target cells.

PMID- 8263932
TI  - Crystallization and preliminary X-ray studies of wild type and catalytic-site
      mutant alpha-amylase from Bacillus subtilis.
AB  - Recombinant alpha-amylase (EC3.2.1.1) from Bacillus subtilis has been
      crystallized by the hanging drop vapor diffusion method using polyethylene glycol
      as precipitant. Crystals of wild-type protein diffract to at least 2.2 A
      resolution, and belong to the space group P2(1)2(1)2(1) with a = 72.2 A, b = 74.9
      A, c = 116.1 A with probably one molecule in the asymmetric unit. A catalytic
      site mutant created by site-directed mutagenesis has also been grown as
      isomorphous crystals with a = 72.6 A, b = 74.4 A, c = 116.7 A. Structural studies
      of both wild-type and mutant proteins will provide a basis for understanding the
      catalytic mechanism of alpha-amylase.

PMID- 8263933
TI  - Molecular cloning of a P-type ATPase gene from the cyanobacterium Synechocystis
      sp. PCC 6803. Homology to eukaryotic Ca(2+)-ATPases.
AB  - With oligonucleotide primers derived from P-type ATPase genes of different
      sources, a part of Synechocystis sp. PCC 6803 genomic DNA was amplified and used
      as hybridization probe for the Synechocystis gene. A 4.7 kb HindIII fragment was
      cloned and sequenced; it contains the open reading frame of the E1E2-ATPase. The
      Synechocystis ATPase (named PMA1) consists of 915 amino acids with a M(r) of
      98,902; it has ten putative transmembrane domains and contains the conserved
      regions a to j common to all P-type ATPases. Its amino acid sequence shows less
      than 20% identity to prokaryotic ATPases but about 30% identity to eukaryotic
      Ca(2+)-ATPases. An alignment to rat kidney and yeast Ca(2+)-ATPase protein
      sequences shows homology in stalk regions and transmembrane domains domains which
      are thought to be involved in calcium binding and transport; these three ATPases
      reveal very similar hydropathy plots and form a separate group in the
      phylogenetic tree of P-type ATPases. The results strongly support the assumption
      that PMA1 of Synechocystis is a calcium translocating ATPase, possibly involved
      in regulatory processes with calcium as second messenger.

PMID- 8263934
TI  - Molecular cloning and developmental expression of the alpha-2 tubulin gene of
      Caenorhabditis elegans.
AB  - Alpha tubulin isotypes are encoded by at least four genes designated alpha-1 to
      alpha-4 in the nematode Caenorhabditis elegans. We describe here, molecular
      cloning of the alpha-2 tubulin gene, located on chromosome I, that encodes a
      protein of 449 amino acids that has high homology to human, mouse and Drosophila
      alpha tubulins, but relatively lower homology to the yeast alpha tubulins. The
      alpha-2 tubulin gene is trans-spliced to the SL1 leader sequence. Northern
      analysis shows that the gene is increasingly transcribed during the early (L1-L3)
      larval stages but has a lower level of transcription in L4 L4 larvae, adults, and
      embryos. Using an alpha-2-lacZ fusion gene expression in transgenic animals, we
      show that the gene is expressed in a tissue-specific manner in the intestine,
      pharyngeal muscle cells, and a subset of neurons which include a class of DB and
      VB motor neurons in the ventral nerve cord, posterior touch receptor neurons,
      PLML, PLMR, in the lumbar ganglia; PVT in the pre-anal ganglion, and ALA in the
      dorsal ganglion in the head. Our results support the notion that tubulin
      structure may contribute to the functional specialization of microtubules.

PMID- 8263935
TI  - Divergent evolution of an "orphon" histone gene cluster in Chironomus.
AB  - The histone genes of the midge Chironomus thummi thummi are organized in tandemly
      repeated gene groups, each containing the four core histone genes plus an H1
      gene. These repetitive gene groups are found at five different loci, linked on
      one chromosomal arm. In addition to the clustered gene groups an isolated histone
      gene group exists which is found spatially separated on a different chromosome
      ("orphon" gene group). These orphon genes have been cloned and analysed in
      detail. Nucleotide sequence and in situ hybridization data suggest that the
      orphon gene group was established early during chironomid speciation, possibly by
      a transposition-like mechanism. This allowed the genes to be moved as an integer
      group. The comparison of orphon and "clustered" histone genes in C. thummi thummi
      indicates that the early spatial separation of the orphon genes from their
      tandemly organized relatives may have stimulated divergent sequence evolution.
      This is particularly true for the orphon H1 gene, which has diverged considerably
      by unusual mutation mechanisms. The translocation of normally clustered genes to
      new genomic sites may favour the generation of sequence variants, which could
      fulfill specialized functional tasks.

PMID- 8263936
TI  - The DNA sequence of adenovirus type 40.
AB  - The 34,214 bp DNA sequence of adenovirus type 40 strain Dugan was determined
      directly from random fragments of virion DNA cloned into a bacteriophage M13
      cloning vector. The gene layout is similar to that of other human adenoviruses,
      and in addition contains two potential protein-coding regions that are conserved,
      but have not been recognized previously, in other adenovirus genomes. One is
      oriented rightward, contained within the intron in the protein-coding region for
      the L4 33K gene, and would encode a protein sharing N-terminal sequence with 33K.
      The other is a leftward oriented exon located between the E3 and L5 IV (fibre)
      regions which would specify the N terminus of a novel protein. The region
      encoding the C terminus of this protein is not apparent from sequence data.

PMID- 8263937
TI  - Suppression of bacteriophage T7 ssb mutation with host ssb.
AB  - Three new mutants of bacteriophage T7 gene 2.5, which encodes a single-stranded
      DNA-binding protein (ssb), were isolated and characterized. One of them, ts2.5,
      which showed temperature-sensitive growth, was found to have two mutations in the
      gene: one a missense mutation generating a Gly143-->Ser change, and the other an
      amber mutation at Tyr215. The other two mutants (am2.5-1 and am2.5-2) had amber
      mutations at Tyr15 and Ser201, respectively. None of these mutants produced a
      significant number of viable progeny under restrictive conditions, irrespective
      of whether the Escherichia coli ssb protein was functional. However, another gene
      2.5 mutant, up2, which we had isolated previously, was found to be dependent on
      the function of host ssb for growth. Further analysis of the up2 mutation
      revealed that it had two additional mutations at genes 6 and 18 besides an opal
      mutation, op1, in gene 2.5. Neither of the suppressor mutations for the op1
      mutation suppressed other gene 2.5 mutations, ts2.5 and am2.5-2. A mutant having
      the op1 mutation alone was unable to grow on nonsense suppressor-free hosts
      regardless of the presence of host ssb. These results indicate that the
      suppressors are specific for the op1 mutation and can make the host ssb usable
      during T7 phage development.

PMID- 8263938
TI  - Structural features of the 26 S proteasome complex.
AB  - Proteasomes play a key role in the degradation of abnormal proteins, of short
      lived regulatory proteins and in antigen processing. Evidence is accumulating
      that the 20 S proteasome represents the proteolytic core of the 26 S protease
      complex (26 S proteasome) which contains several additional subunits implicated
      in regulation and substrate recognition. Using electron microscopy and digital
      image analysis we obtained first insights into the structure of this complex
      which has an estimated molecular weight of approximately 2000 kDa. Two highly
      asymmetric masses which presumably contain the regulatory subunits of the 26 S
      complex are attached to both ends of the dimeric 20 S proteasome clearly
      reflecting its C2 symmetry. The structural uniformity of the complex, i.e. the
      absence of significant inter-image variations, has important implications for the
      structure of the latter: It indicates that, in spite of their sequence
      similarities, the various alpha-type and beta-type subunits of the 20 S
      proteasome are not promiscuous but occupy precisely defined positions.

PMID- 8263939
TI  - Evolution of substrate diversity in the superfamily of amino acid dehydrogenases.
      Prospects for rational chiral synthesis.
AB  - We have analysed the sequence homology between glutamate, leucine and
      phenylalanine dehydrogenases in the light of the solution of the structure of the
      glutamate dehydrogenase from Clostridium symbiosum. This analysis indicates that
      the elements of secondary structure comprising the core of the two domains in
      glutamate dehydrogenase are conserved in the other two enzymes. There is a
      striking conservation of the residues responsible for the recognition of the
      nicotinamide ring of the nucleotide cofactor and the backbone of the amino acid
      substrates. Furthermore, residues involved in a major conformational
      rearrangement on amino acid binding are preserved, as are those implicated in the
      catalytic chemistry. In contrast, the pattern of insertions/deletions between
      these enzymes is consistent with possible differences in quaternary structure.
      Differential substrate specificity between these enzymes is achieved by critical
      substitutions at the base of the binding pocket, which accommodates the side
      chain of the amino acid substrate. This provides insights into the mutations
      necessary to produce new catalysts for the chiral synthesis of novel amino acids.

PMID- 8263940
TI  - Shape complementarity at protein/protein interfaces.
AB  - A new statistic Sc, which has a number of advantages over other measures of
      packing, is used to examine the shape complementarity of protein/protein
      interfaces selected from the Brookhaven Protein Data Bank. It is shown using Sc
      that antibody/antigen interfaces as a whole exhibit poorer shape complementarity
      than is observed in other systems involving protein/protein interactions. This
      result can be understood in terms of the fundamentally different evolutionary
      history of particular antibody/antigen associations compared to other systems
      considered, and in terms of the differing chemical natures of the interfaces.

PMID- 8263941
TI  - The limits of protein secondary structure prediction accuracy from multiple
      sequence alignment.
AB  - The expected best residue-by-residue accuracies for secondary structure
      prediction from multiple protein sequence alignment have been determined by an
      analysis of known protein structural families. The results show substantial
      variation is possible among homologous protein structures, and that 100%
      agreement is unlikely between a consensus prediction and one member of a protein
      structural family. The study provides the range of agreement to be expected
      between a perfect secondary structure prediction from a multiple alignment and
      each protein within the alignment. The results of this study overcome the
      difficulties inherent in the use of residue-by-residue accuracy for assessing the
      quality of consensus secondary structure predictions. The accuracies of recent
      consensus predictions for the annexins, SH2 domains and SH3 domains fall within
      the expected range for a perfect prediction.

PMID- 8263942
TI  - The contribution of contact and non-contact residues of antibody in the affinity
      of binding to antigen. The interaction of mutant D1.3 antibodies with lysozyme.
AB  - We have analysed the contribution of residues of the D1.3 Fv fragment to binding
      of hen egg lysozyme. We altered residues at the contact interface by site
      directed mutagenesis, and determined the affinity of the mutant Fv fragments for
      lysozyme by fluorescence quench titration. We found that a band of residues at
      the centre of the contact interface were much more important for binding affinity
      than those at the periphery. We also subjected the seFv fragment to random
      mutagenesis to simulate somatic mutation and affinity maturation. By display of
      the mutants on the surface of filamentous phages, and selection of the phages
      with biotinylated lysozyme, we were able to select mutants with modest
      improvements in binding affinity to lysozyme. By combining the mutations we
      obtained a scFv fragment with a fivefold improved affinity (Kd approximately 0.6
      nM compared to wild-type Kd = 3.3 nM). However, none of the altered residues
      leading to improved affinity was located in the contact interface. This indicates
      that the interactions of a few residues at the centre of the contact interface
      are responsible for the binding affinity to antigen, but that these interactions
      can be modulated by alterations of residues outside the binding site. This may
      represent a typical mechanism for the affinity maturation of antibodies.

PMID- 8263943
TI  - Overproduction and purification of native and queuine-lacking Escherichia coli
      tRNA(Asp). Role of the wobble base in tRNA(Asp) acylation.
AB  - Escherichia coli tRNA(Asp) was overproduced in E. coli up to 15-fold from a
      synthetic tRNA(Asp) gene placed in a plasmid under the dependence of an isopropyl
      beta,D-thiogalactopyranoside-inducible promoter. Purification to nearly
      homogeneity (95%) was achieved after two HPLC DEAE-cellulose columns. E. coli
      tRNA(Asp)[G34] (having guanine instead of queuine at position 34) was obtained by
      the same procedure except that it was overproduced in a strain lacking the enzyme
      responsible for queuine modification. Nucleoside analysis showed that, except for
      the replacement of Q34 by G34 in mutant-derived tRNA(Asp), the base modification
      levels of both tRNAs are the same as those in wild-type E. coli tRNA(Asp).
      Kinetic properties of tRNA(Asp)[Q34] and [G34] with yeast AspRS compared to those
      in the homologous reactions in yeast and E. coli clearly indicate that the major
      identity elements are the same in both organisms: the conserved discriminant base
      and the anticodon triplet. In connection with this, we explored by site-directed
      mutagenesis the functional role of the interactions which, as revealed by the
      crystallographic structure, occur between the wobble base of yeast tRNA(Asp) and
      two residues of yeast AspRS. Their absence strongly affected aspartylation and
      the kd of tRNA(Asp). Each contact individually restores almost completely the
      wild-type acylation properties of the enzyme; thus, wobble base recognition in
      yeast appears to be more protected against mutational events than in E. coli,
      where only one contact is thought to occur at position 34.

PMID- 8263944
TI  - Genomic footprinting of the promoter regions of STE2 and STE3 genes in the yeast
      Saccharomyces cerevisiae.
AB  - Dimethyl sulfate, DNase I and micrococcal nuclease DNA cleavage were combined
      with the ligation-mediated polymerase chain reaction to obtain high resolution
      maps of the promoter regions for two cell-type-specific genes: the a-specific
      STE2 gene and the alpha-specific STE3 gene. We find that MCM1 binds in vivo in a
      cells to a 16 bp P-box sequence located in the STE2 UAS. In alpha-cells, the
      footprint pattern is extended relative to a-cells, consistent with the additional
      binding of MAT alpha 2 to the sequences flanking each end of the P-box. A
      nucleosome was found adjacent to the P-box of the transcriptionally repressed a
      specific STE2 UAS in alpha-cells, positioned so that the nucleosome overlaps the
      TATA-box. In contrast, such well-positioned nucleosomes were not found for the
      transcriptionally active STE2 UAS in a-cells, where instead the TATA box appears
      to be bound to the general transcription factor TFIID. These observations support
      the hypothesis that MAT alpha 2 repression of a-specific genes is mediated by
      nucleosomes, perhaps by exclusion of TFIID from the TATA-box.

PMID- 8263945
TI  - Functional dissection of two promoters that control sense and antisense
      transcription of Drosophila melanogaster F elements.
AB  - Drosophila melanogaster F elements are members of the super-family of LINEs,
      mobile repeated DNA sequences that lack LTRs and propagate by the reverse
      transcription of unit-length RNA intermediates. The F 5' end region harbours two
      promoters (F(in) and F(out)) that transcribe in a convergent manner. Each
      promoter has been functionally dissected by assaying in D. melanogaster cultured
      cells templates carrying base substitutions and/or deletions across the +1 to
      +245 region of the element F12. F(in), that likely controls the synthesis of gene
      products and transposition intermediates, is internal to the transcribed region.
      Two elements play a major role in F-sense transcription. The proximal element
      spans the interval +6 to +14 and includes a major RNA start site. Heterologous
      DNA featuring a nearly identical purine-pyrimidine sequence can functionally
      replace the initiator-like module only when properly spaced from downstream F
      sequences. The distal element is within the interval +18 to +46 and may
      correspond to a motif (AGACGTTT, +34 to +41) conserved in other Drosophila LINEs.
      F(out) is a TATA-less promoter that directs transcription predominantly from
      three nearby sites (a to c). F(out) expression is influenced by multiple elements
      located upstream of residue -68 relative to site a as +1 within a region (alpha)
      shown to stimulate the D. melanogaster hsp70 promoter in an orientation and
      position-independent fashion. Changes within the -43 to +24 interval may suppress
      or stimulate transcription from sites a and c. Initiation from a site
      approximately 30 nucleotides upstream of site a is enhanced by alterations of the
      interval -43 to -5. The expression of the two F promoters, determined by the
      interaction of the transcriptional machinery with distinct DNA sequences, is
      influenced by a common element within the alpha region.

PMID- 8263946
TI  - Changes in geometry of actively shortening unipennate rat gastrocnemius muscle.
AB  - Muscle geometry of the unipennate medial gastrocnemius (GM) muscle of the rat was
      examined with photographic techniques during isometric contractions at different
      muscle lengths. It was found that the length of fibers in different regions of GM
      differs significantly, and proximal aponeurosis length varies significantly from
      distal aponeurosis length; the angle of the aponeurosis with the muscular action
      differs significantly among regions at short muscle lengths (full contraction).
      These data support the idea that the unipennate GM cannot be represented by a
      parallelogram in a two-dimensional analysis. As the muscle shortens, the area of
      the mid-longitudinal plane of the GM decreases by 24%, a decrease that may be
      explained by assuming fiber diameter to increase in all directions. The angle
      between fiber and aponeurosis is determined by more than fiber length. Hence,
      such important assumptions as a parallelogram with constant area and fiber angle
      gamma changes determined by fiber length changes, frequently used in the
      theoretical analysis of the morphological mechanism of unipennate muscle
      contraction, do not hold for the unipennate GM of the rat. Length of the
      sarcomere within the mid-longitudinal plane of GM varies from 1.92 to 2.14
      microns among the different muscle regions at muscle optimum length (length at
      which force production is highest), whereas shortening to 6 mm less than optimum
      length produces a range of sarcomere lengths from 0.89 to 1.52 microns. These
      data suggest that fibers located in different regions of the GM reach their
      optimum and slack lengths at various muscle lengths.

PMID- 8263947
TI  - Preferential expression of HSC70 heat shock mRNA in gerbil heart after transient
      brain ischemia.
AB  - Inductions of mRNAs for heat shock protein (HSP) 70 and heat shock cognate
      protein (HSC) 70 were examined in the cerebral cortex, cerebellum, heart, lung,
      kidney, and liver of gerbils after a 10-min transient forebrain ischemia. HSP70
      mRNA was normally expressed in a small amount in the cerebellum, lung, and
      kidney, but was not expressed in the heart or liver in a detectable amount. A
      very small amount of HSP70 mRNA was also present in the cerebral cortex. HSC70
      mRNA was normally present in all the organs examined with a variety in the
      amount. Eight hours after the cerebral ischemia, the level of HSP70 mRNA
      increased in the cerebral cortex, lung, and kidney. HSC70 mRNA levels also
      increased in all the organs. However, the increase of HSC70 mRNA was remarkable
      in the heart. Transient cerebral ischemia caused subsequent hyperthermia.
      Treatment of gerbils with an artificial hyperthermia without cerebral ischemia
      increased the HSP70 and HSC70 mRNA levels as well. However, the HSC70 mRNA level
      in the heart after cerebral ischemia was much higher than that in the case with
      hyperthermic treatment. These results suggest that HSC70 mRNA was preferentially
      induced in the heart after transient forebrain ischemia that was not only due to
      the subsequent hyperthermia.

PMID- 8263948
TI  - Expression of c-fos and related genes in the rat heart in response to
      norepinephrine.
AB  - We have investigated the cellular and regional localization of Fos-like
      immunoreactivity (FLI) in the rat heart in response to the hypertrophic hormone
      norepinephrine (NE). Previous studies have demonstrated elevated c-fos mRNA
      levels in the rat heart following this treatment but have not shown which cell
      type(s) or specific chamber(s) of the heart contribute to the response in vivo,
      or whether Fos protein is actually produced. Administration of a single injection
      of NE (2.5 mg/kg) or chronic infusion of NE (100 micrograms/kg/h) led to an
      increase in Fos-like immunoreactivity in the nuclei of cardiac myocytes and
      vascular smooth muscle cells compared to control tissue. The response was
      transient with maximal immunoreactivity observed 2-3h following treatment,
      falling to near basal levels in most regions of the heart after 6 h. Although all
      chambers of the heart contributed to the response, greatest Fos-like
      immunoreactivity was observed in the left atrium and left ventricle, with
      intermediate levels found in the septum and right ventricle, and lowest levels in
      the right atrium. Fos-like immunoreactivity observed in the left atrium was
      accompanied by elevated mRNA levels of fra-1 and fra-2 but not c-fos itself
      indicating that a related gene product other than Fos contributed to the observed
      response. Experiments with the Langendorff perfused rat heart showed that NE and
      elevated perfusion pressure independently increased both c-fos mRNA and FLI. This
      work is the first evidence for a direct action of NE on Fos expression in adult,
      as opposed to neonatal, cardiomyocytes. These results lend further support to the
      notion that Fos and related gene products mediate some of the hypertrophic
      actions of norepinephrine.

PMID- 8263949
TI  - The isolation of adult rat cardiomyocytes activates inositol(1,4,5) trisphosphate
      3'kinase activity.
AB  - Addition of norepinephrine to [3H]inositol-labeled rat hearts or isolated left
      atria caused the release of inositol(1,4,5)trisphosphate which was metabolized by
      dephosphorylation to inositol(4)monophosphate. Products of the
      inositol(1,4,5)trisphosphate 3'-kinase pathway were not present at detectable
      levels. When norepinephrine was added to [3H]inositol-labeled isolated adult
      cardiomyocytes the released inositol(1,4,5)trisphosphate was metabolized
      partially by phosphorylation as evidenced by the presence of the immediate
      phosphorylation product inositol(1,3,4,5)-tetrakis-phosphate and its
      dephosphorylation products inositol (1,3,4)trisphosphate and inositol(1,3)
      bisphosphate. Direct measurement of inositol trisphosphate 3'-kinase activity in
      cytosols prepared from intact hearts and isolated myocytes demonstrated
      activation of the enzyme during cell isolation from 20 +/- 0.5 p mol/min/mg
      protein to 124 +/- 14 (mean +/- S.E.M., n = 3, P < 0.001). These data show that
      the kinase pathway is suppressed in healthy heart tissue and show that it can be
      activated under conditions such as those required for cell isolation.

PMID- 8263950
TI  - Temperature affects human cardiac sarcoplasmic reticulum energy-mediated calcium
      transport.
AB  - Hypothermic cardioplegic solutions are currently used to preserve cardiac
      function during transportation. However, it has been shown that end-diastolic
      compliance decreases in donor hearts during reperfusion. Excessively cold
      temperatures may affect membrane-bound enzymes (Ca2+ ATPase and Ca2+ uptake)
      which are necessary for calcium homeostasis. To study the effect of temperature
      on Ca2+ ATPase and Ca2+ uptake activities over the temperature range to which a
      donor heart is usually exposed (4 degrees-37 degrees C), sarcoplasmic reticulum
      (SR) was isolated from human atrial appendages. SR was also isolated from atrial
      appendages which had been stored in saline at 4 degrees C for 4 or 24 h or 24 h
      in St Thomas' cardioplegic solution (ST). Ca2+ ATPase and Ca2+ uptake from these
      samples were compared with those found in the SR of unstored appendages. The
      activity of Ca2+ uptake and Ca2+ ATPase showed great sensitivity at assay
      temperatures below 22 degrees C, while no such sensitivity was identified in SR
      NADPH/cytochrome C reductase (NCR). After storage of atrial appendages for only 4
      h in saline at 4 degrees C, Ca2+ uptake activity was reduced 50% in the SR when
      compared to unstored controls (80 +/- 9.9 nmol/mg/min and 155.24 +/- 2.4
      nmol/mg/min, respectively; P < 0.02) whereas Ca2+ ATPase was not affected until
      24 h of storage, when the activity was also decreased > 50% (P = 0.0002).
      However, NCR was not affected. In addition, storage at 4 degrees C significantly
      decreased the SR protein yield (mg/g homogenate protein) at 4 or 24 h in saline
      as well as 24 h in ST. However, there was no decrease in the enzyme activities
      (Ca2+ ATPase, 229 +/- 25.3; Ca2+ uptake, 221 +/- 27.1; NCR, 24.9 +/- 0.48
      nmol/mg/min). Following exposure to low temperature, alteration of Ca2+ uptake
      and Ca2+ ATPase may result in disruption of calcium homeostasis, thereby
      interrupting excitation-contraction coupling and relaxation. The damaging effects
      of hypothermia should be taken into account when assessing the peri-operative
      complications and the long-term results of cardiac transplantation.

PMID- 8263951
TI  - Factors affecting the activation of glycogen synthase in primary culture
      cardiomyocytes.
AB  - The ability of insulin, IGF-1 and IGF-2 to stimulate the activation of glycogen
      synthase in the heart was compared under completely defined conditions using
      primary culture cardiomyocytes. Both insulin and IGF-1 produced similar time- and
      concentration-dependent activation of glycogen synthase with the maximum
      stimulation observed at 10-15 min following hormone administration and at > or =
      10 nM insulin or IGF-1. IGF-2 was largely ineffective at physiological
      concentrations. When primary culture cardiomyocytes were incubated with 100
      microM palmitate for 2 h and then challenged with various concentrations of
      insulin or IGF-1, there was a significant decrease in the ability of the cells to
      activate glycogen synthase. In addition, maintaining cardiomyocytes in hormone
      deficient culture conditions for 24 or 48 h also resulted in a reduced ability to
      activate glycogen synthase in response to these hormones. These results suggest
      that (1) both insulin and IGF-1 are potent regulators of glycogen synthesis in
      the heart, (2) the enzymes involved in the dephosphorylation (activation) of
      glycogen synthase are closely linked to both insulin and IGF-1, but not IGF-2
      receptor signaling pathways, (3) glycogen synthase activation is adversely
      affected by the maintenance of cardiomyocytes in the presence of palmitate or for
      > or = 24 h in hormone deficient media which results in insulin and IGF-1
      resistance, and (4) this resistance, like that found in cells from diabetic rats,
      is due at least in part to a decrease in glycogen synthase phosphatase activity.

PMID- 8263952
TI  - Lack of change in MnSOD during ischemia/reperfusion of isolated rat heart.
AB  - Decreased endogenous superoxide dismutase (SOD) activity has been implicated in
      free radical-mediated reperfusion injury of the ischemic myocardium. Antioxidant
      enzymes have been added to the modalities of reperfusion therapy of acute
      myocardial infarction based on this observation. We measured the content of MnSOD
      specific protein, activity of Mn and Cu, ZnSODs, and MnSOD mRNA in the working
      isolated rat heart subjected to various durations of ischemia and reperfusion.
      Recovery of mechanical function was monitored and lactate and lactic
      dehydrogenase released in the coronary effluent before and after ischemia were
      measured. In this model with reversible or irreversible myocardial injury, we
      noted no change in the myocardial MnSOD specific protein content and, contrary to
      some previous observations, no change in the activity levels of Mn or Cu,ZnSODs.
      Our results suggest that free radical-mediated damage in the heart during
      ischemia and reperfusion is probably not due to impaired activity or degradation
      of native SODs.

PMID- 8263953
TI  - Alterations in alpha 1-adrenergic receptor-mediated phosphatidylinositol turnover
      in hypoxic cardiac myocytes.
AB  - The purpose of these studies was to examine the effects of hypoxia on alpha 1
      adrenergic receptor (alpha 1AR) mediated phosphatidylinositol (PI) turnover in
      cultured neonatal rat cardiac myocytes. Cells were pre-labeled with [3H]-inositol
      and incubated for 1 h in either normoxia or hypoxia. Phenylephrine, an alpha 1AR
      agonist, was added at various time intervals (0-60 min) before termination of the
      incubation. There was a time-dependent release of radioactivity from the lipid
      fraction to the aqueous fraction with alpha 1AR stimulation. alpha 1AR-mediated
      PI turnover was biphasic in normoxic cells and monophasic in hypoxic cells. Using
      ion-exchange chromatography, radioactivity in the inositol trisphosphate (IP3)
      peak was increased with acute phenylephrine stimulation (5 min) in the normoxic
      cells, while inositol phosphate (IP) and inositol bisphosphate (IP2) were
      increased with chronic stimulation (60 min). After 5 min of alpha 1AR
      stimulation, hypoxia did not alter total aqueous radioactivity when compared to
      normoxia, but there was a significant increase in IP2. However, there was
      decreased PI turnover in chronically stimulated (30-60 min) hypoxic cells when
      compared to normoxic cells. Hypoxia had no effect on radioactivity in the IP3
      fraction with either 0, 5, or 60 min of alpha 1AR stimulation, but there was a
      significant increase in [1,4,5]-IP3 in hypoxic cells with 30 s alpha 1AR
      stimulation. With hypoxia, there was no difference in radioactivity in the
      phosphatidylinositols with either 0 or 5 min stimulation when compared to
      normoxia. However, after 60 min of alpha 1AR stimulation, hypoxia resulted in
      increased PI and PIP, when compared to normoxic cells, but PIP2 radioactivity was
      unchanged. There was no effect of pertussis toxin on either the acute or chronic
      phase of PI turnover, negating involvement of Gi or G(o). These data suggest that
      alpha 1AR stimulation in neonatal rat cardiac myocytes is biphasic, and that
      hypoxia produces a slower monophasic response during extended alpha 1-agonist
      exposure as would be found with ischemia.

PMID- 8263954
TI  - A 13C-NMR study of glucose oxidation in the intact functioning rat heart
      following diabetes-induced cardiomyopathy.
AB  - A causative factor in the development of diabetes-induced heart dysfunction may
      be abnormalities in myocardial energy metabolism. Using 13C-NMR spectroscopy, we
      investigated the effects of experimentally induced diabetes (streptozotocin 65
      mg/kg, i.v.) on glucose metabolism and contractile function in the isolated
      perfused rat heart. Hearts from streptozotocin-treated and untreated control rats
      were perfused with 11 mM [1-13C]glucose as substrate and 1H-decoupled 13C-spectra
      recorded for up to 90 min. Incorporation of label from [1-13C]glucose into
      lactate and glutamate was observed in hearts from control animals, consistent
      with metabolism through glycolysis and TCA cycle, respectively. Diabetic hearts
      did not incorporate label into lactate or glutamate. Addition of insulin (0.05
      U/ml) to the buffer resulted in the appearance of [3-13C]lactate, although
      glutamate labeling was not observed. Addition of insulin plus dichloroacetate (2
      mM) resulted in incorporation of label from [1-13C]glucose into 2-, 3- and 4-13C
      glutamate, indicating glucose entry into the TCA cycle. Addition of insulin, or
      insulin plus dichloroacetate to control hearts did not alter labeling of either
      lactate or glutamate. Cardiac function in hearts from the diabetic group was
      depressed compared to controls and declined significantly over the duration of
      the experiment. These studies show that concomitant with a decrease in cardiac
      function, glucose oxidation is profoundly inhibited following the induction of
      diabetes with streptozotocin. These observations are consistent with a
      combination of decreased glucose transport and a decrease in pyruvate
      dehydrogenase activity.

PMID- 8263956
TI  - Beneficial effects of quinidine on post-ischemic contractile failure of isolated
      rat hearts.
AB  - The present study was undertaken to determine whether quinidine may improve
      ischemia/reperfusion-induced functional and metabolic injury of isolated rat
      hearts. Thirty-five-min ischemia and the subsequent 60-min reperfusion resulted
      in no post-ischemic force generation, an increase in left ventricular end
      diastolic pressure (about 1500%) and a sustained rise in perfusion pressure (136
      +/- 15% of initial). This was associated with an increase in the release of
      creatine kinase and ATP metabolites from the reperfused heart, a decrease in
      tissue high-energy phosphates, changes in tissue sodium, calcium, potassium and
      magnesium contents, and a reduction in the triphenyltetrazolium chloride (TTC)
      stained area, an indicator of infarction. Hearts were treated with 3-100 microM
      quinidine 3 min before ischemia. Quinidine at concentrations of 10 microM or
      greater resulted in post-ischemic contractile recovery in a concentration
      dependent manner (61 +/- 8 to 95 +/- 8% of initial). Ischemia/reperfusion-induced
      metabolic and histologic alterations were also suppressed by treatment with
      quinidine in a concentration-dependent manner. The results suggest that quinidine
      has a cardioprotective effect in ischemic/reperfused hearts. Because
      transmembrane fluxes of ions, substrates, and enzymes were suppressed by
      treatment with quinidine, protection of cardiac cell membrane function and/or
      integrity against ischemia/reperfusion-induced ionic imbalance, presumably sodium
      imbalance, across the sarcolemma is a possible mechanism by which quinidine may
      act. Slightly higher levels of ATP were detected in the treated hearts at 10 and
      15 min, but not at 35 min of ischemia. Such preservation of high-energy
      phosphates might also be beneficial for protecting myocardial cells against
      ischemic damage.

PMID- 8263955
TI  - The cellular basis for the blunted response to beta-adrenergic stimulation in
      supraventricular tachycardia-induced cardiomyopathy.
AB  - Chronic tachycardia-induced dilated cardiomyopathy causes increased plasma
      catecholamines and alterations in beta-adrenergic responsiveness in vivo.
      However, whether isolated myocyte contractile response to beta-stimulation is
      directly affected by the development of cardiomyopathy and how these changes are
      related to alterations in the beta-adrenergic receptor system remain unclear.
      Accordingly, isolated myocyte function and beta-adrenergic responsiveness were
      examined in two groups of 12 pigs each: sham controls, and with supraventricular
      tachycardia induced cardiomyopathy (SVT; pace: 240 beats/min, 3 weeks). Isolated
      LV myocyte percent and velocity of shortening were examined at baseline, with
      isoproterenol (2-100 nM), and forskolin (0.1-4 microM). Baseline percent and
      velocity of shortening were significantly reduced with SVT compared to controls
      (1.6 +/- 0.1 vs 5.4 +/- 0.2%, 56 +/- 3 vs 25 +/- 1 micron/s, respectively, P <
      0.05). The maximal increase in the percent and velocity of shortening with
      isoproterenol was significantly blunted in the SVT myocytes compared with
      controls (3.2 +/- 0.4 vs 9.7 +/- 1.0%, 48.0 +/- 5.3 vs 122.6 +/- 15.5 micron/s,
      respectively, P < 0.05). Similarly, maximal increase in the percent and velocity
      of shortening with forskolin were reduced with SVT compared to controls (3.3 +/-
      0.4 vs 10.5 +/- 0.6%, 50.7 +/- 6.4 vs 120.1 +/- 9.7 micron/s, respectively, P <
      0.05). In order to determine the cellular basis for these changes in beta
      adrenergic response, myocyte structure, sarcolemmal beta-receptor density and
      affinity, and adenylate cyclase activity were examined. There was a 25% reduction
      in beta-receptor number with SVT (P < 0.05) but no change in affinity. Basal
      adenylate cyclase activity was lower with SVT compared to control (46 +/- 3 vs 77
      +/- 10 pmol cyclic AMP/mg/min, P < 0.05), and exhibited a blunted response with
      both isoproterenol (1 mM; 106 +/- 19 vs 203 +/- 26 pmol cyclic AMP/mg/min, P <
      0.05) and forskolin (100 microns: 209 +/- 35 vs 378 +/- 58 pmol cyclic
      AMP/mg/min, P < 0.05). Finally, myofibrillar content within SVT myocytes was
      significantly reduced from controls (43 +/- 7 vs 63 +/- 4%, P < 0.05). In
      summary, the cellular basis for the depressed myocyte contractile response to
      beta-stimulation with tachycardia induced SVT are probably due to several factors
      which include: decreased expression of beta-receptors, alterations in beta
      receptor transduction, reduced adenylate cyclase activity, and decreased myocyte
      contractile protein content.

PMID- 8263957
TI  - Heart muscle cells acutely infected with Trypanosoma cruzi: characterization of
      electrophysiology and neurotransmitter responses.
AB  - Primary cell cultures of mouse ventricular myocardium were infected with
      Trypanosoma cruzi, to study the consequences of T. cruzi-muscle cell interaction
      on the rate of spontaneous contractions, on the responses to norepinephrine, and
      on action potential parameters. Single cells or small cell groups of infected
      cultures were subjected to pharmacological and electrophysiological experiments.
      In concentrations ranging from 1 nM to 100 microM, norepinephrine exerted
      positive or negative chronotropic effects mediated by alpha-adrenergic receptors.
      A significant number of infected cells (25%) did not respond to the agonist. Two
      days after infection the cultures exhibited a higher frequency of spontaneous
      contractions (20%), paralleled by an increase in firing rate and a decrease in
      the action potential duration without significant changes in maximum diastolic
      potential and action potential amplitude. A decrease in alpha-adrenergic receptor
      mediated positive chronotropic response to norepinephrine was also observed in 2
      day infected cells. Cells made to phagocyte ferritin particles showed an increase
      in the rate of spontaneous contractions, but no changes in the positive
      chronotropic responses to norepinephrine. In conclusion, these observations show
      that during acute infection with T. cruzi, there are alterations in automaticity
      and in the chronotropic responses to norepinephrine, whose mechanisms are related
      to the process of parasite endocytosis by the cardiac cells.

PMID- 8263958
TI  - Effect of membrane incorporation of 1-palmitoylcarnitine on surface charge of
      human erythrocytes.
AB  - 1-Palmitoylcarnitine (1-PC) reduced the electrophoretic mobility of human
      erythrocytes bathed in low ionic strength solution. Unlike divalent cations which
      appear to reduce electrophoretic mobility by screening surface negative charge,
      cationic 1-PC does so by being incorporated into the plasma membrane.
      Incorporation of 1-PC was assessed directly by measurement of the partition
      coefficients which are 1.18 x 10(5) and 1.38 x 10(5) in sarcoplasmic reticulum
      vesicles and erythrocyte ghosts, respectively. The hydrophobic nature of the
      amphiphile interaction with erythrocyte membrane was also evident as an
      antihemolytic effect at 1-PC concentrations that also reduced electrophoretic
      mobility. Moreover, the potency and efficacy of acylcarnitines to reduce
      electrophoretic mobility increased as the acyl chain length increased. 1-PC also
      reduced the electrophoretic mobility of guinea-pig ventricular myocytes in low
      ionic strength solution. Estimation of the zeta potential yielded positive shifts
      of 4 mV in myocytes and 5 mV on erythrocytes at 1 microM 1-PC. These voltage
      shifts are essentially the same as those reported for activation and inactivation
      of sodium and calcium currents in myocytes. Therefore, the surface charge effect
      of 1-PC depends upon membrane incorporation and underlies the
      electrophysiological actions of the amphiphile including arrhythmias.

PMID- 8263959
TI  - A human heart cDNA library--the development of an efficient and simple method for
      automated DNA sequencing.
AB  - A direct polymerase chain reaction (PCR) amplification of the human heart cDNA
      clones was used to generate lambda PCR product. By the use of the first set of
      primers derived from lambda gt11, each cDNA insert can readily be obtained. Using
      millipore filters, primers and nucleotides are removed and this purified PCR
      product can then be subjected to a second set of fluorescent primers in the
      generation of nucleotides in the auto-cycle reactions for automated DNA
      sequencing.

PMID- 8263960
TI  - Regulation of the endothelin-1 transmembrane signaling pathway: the potential
      role of agonist-induced desensitization in the coronary artery of the rapid
      ventricular pacing-overdrive dog model of heart failure.
AB  - This study examined the potential role of ET-1 and the contribution of protein
      kinase C (PKC) in the desensitization of the ET-1 transmembrane signaling pathway
      in the left circumflex coronary artery (CCA) of a dog model of congestive heart
      failure (CHF). In the CCA of the rapid ventricular pacing-overdrive dog model of
      CHF, elevated plasma endothelin levels were associated with a decrease in the
      basal accumulation of inositol phosphates and ET-1 mediated activation of
      phosphatidylinositol (PI) turnover (P < 0.05). To assess whether elevated plasma
      ET-1 levels may have contributed to the diminished ET-1 responsiveness in the
      heart failure dogs, ET-1 generation of inositol phosphates was measured following
      a one hour pretreatment of normal coronary artery rings with 0.1 nM ET-1. As
      compared to non-treated rings, ET-1 pretreatment resulted in a 33% decrease of ET
      1 (10 nM) production of inositol phosphates. To evaluate the role of PKC in this
      process, normal coronary rings pretreated for a period of one hour with the
      phorbol ester, phorbol 12-myristate 13-acetate (PMA, 1 microM), resulted in a
      similar attenuation (36%) of ET-1 production of inositol phosphates. In the
      presence of the protein kinase C inhibitor staurosporine, both the agonist and
      phorbol ester induced decreases in ET-1 mediated PI turnover were reversed.
      Staurosporine even potentiated (75%) ET-1 induced PI turnover despite ET-1 and
      PMA pretreatments. These results suggest that agonist-induced desensitization of
      ET-1 mediated PI turnover can occur and is at least one of the possible
      mechanisms contributing to the desensitization of the ET-1 transmembrane
      signaling pathway in the pacing-overdrive model of heart failure in the dog.

PMID- 8263961
TI  - Effects of endogenous and exogenous lysophosphatidylcholine in isolated perfused
      rat hearts.
AB  - In isolated Langendorff perfused rat hearts, treatment with exogenous palmitoyl
      lysophosphatidylcholine (P-LPC; 3-50 microM) under normoxic conditions, resulted
      in reduced heart rate (HR), coronary flow (CF) and contractile function. After 30
      min Krebs perfusion, following P-LPC infusion, HR and CF remained reduced and
      contractile function continued to deteriorate. End diastolic pressure (EDP) and
      lactate dehydrogenase (LDH) release in LPC treated hearts were significantly
      increased from controls. Myocardial lysophosphatidylcholine (LPC) levels after 25
      min global ischemia were significantly higher than controls (463 +/- 10 for
      control vs 550 +/- 15 nmol/g dry wt for ischemia). Following 30 min reperfusion
      an increase from control was still observed (475 +/- 11 for control vs. 594 +/-
      17 for ischemia+reperfusion). Analysis of molecular species of LPC demonstrated
      that palmitoyl, oleoyl and stearoyl were increased after 25 min ischemia. After
      30 min of reperfusion only palmitoyl and stearoyl were significantly increased.
      After 25 min treatment with 3 microM P-LPC and 30 min normoxic perfusion,
      myocardial LPC was three-fold higher than after 25 min ischemia. Treatment with
      0.2 microM exogenous P-LPC resulted in myocardial tissue LPC levels (562 +/- 23)
      equivalent to those seen after 25 min ischemia (550 +/- 15). Compared to time
      matched controls hearts perfused with 0.2 microM P-LPC displayed no significant
      reductions in contractile function nor increase in LDH release. Thus, in isolated
      rat hearts, the increase in LPC seen after 25 min of global ischemia may not
      solely mediate the contractile dysfunction and LDH release observed.

PMID- 8263962
TI  - Adenosine contributes to neutrophil-mediated loss of myocardial function in post
      ischemic guinea-pig hearts.
AB  - Tissue injury associated with myocardial ischemia is assumed to largely result
      from the toxic effects of active oxygen species generated by accumulated
      polymorphonuclear leukocytes (PMNs). Recent reports have indicated that adenosine
      can interfere with the PMN function in vitro. The potential of adenosine to
      influence PMN-mediated myocardial tissue injury was assessed using a model of
      ischemia-reperfusion injury developed in the isolated working guinea-pig heart
      perfused with homologous PMNs. After an initial work phase, hearts were subjected
      to 30 min low-flow ischemia (1 ml/min) in the absence and presence of PMNs. Work
      was resumed after 15 min reperfusion in a non-working mode (Langendorff).
      Adenosine in the coronary effluent reached a maximum of 0.2 microM during low
      flow ischemia. Recoveries of external heart work and cardiac output were reduced
      from about 80% to about 40% by PMNs. Infusion of adenosine deaminase (ADA, 5
      U/ml), theophylline (50 microM) or the selective A1-antagonist dipropyl-8
      cyclopentylxanthine (0.1 microM) prevented this effect. Furthermore, application
      of adenosine (0.1 microM) in combination with PMNs also resulted in a loss of
      pump function, even in the absence of a direct ischemic stimulus. The data
      indicate that adenosine contributes to post-ischemic, PMN-mediated damage in the
      isolated working guinea-pig heart model by a receptor-mediated action.

PMID- 8263963
TI  - Effect of isoproterenol on coronary blood flow and signal transduction responses
      in thyroxine-treated rabbit hearts.
AB  - This study examined the hypothesis that treatment with thyroxine (T4) would alter
      the coronary blood flow and signal transduction responses of the rabbit heart. T4
      was administered for 16 days by subcutaneous time-release pellets (3 mg/kg/day)
      in 3 kg New Zealand white rabbits. Four groups of anesthetized open-chest rabbits
      (control, control+isoproterenol (ISO, 0.5 microgram/kg/min for 15 min), T4, and
      T4 + ISO) were used to determine coronary blood flow (radioactive microspheres),
      cyclic AMP content (competitive binding), low Km cyclic-AMP-phosphodiesterase
      activity (cyclic AMP-PDE, conversion of 3H-cyclic AMP to 3H-AMP) and beta
      adrenoceptor number and affinity (125I-iodocyano-pindolol). Coronary blood flow
      was increased from control by ISO from 167 +/- 59 to 354 +/- 157 ml/min/100 g. T4
      did not cause cardiac hypertrophy, but increased baseline coronary blood flow to
      269 +/- 115 ml/min/100 g. The ISO response was attenuated in terms of blood flow
      (448 +/- 118) and heart rate with T4. Beta-adrenoceptor numbers increased
      significantly from 65.7 +/- 9.2 to 81.9 +/- 4.4 fmol/mg protein, while neither
      soluble (126 +/- 39 vs 119 +/- 15 pmol/mg protein/min) nor particulate cyclic AMP
      PDE activity were different between control and T4 animals. Cyclic AMP content
      was increased from control by both ISO (779 +/- 239 to 1371 +/- 672 pmol/g) and
      T4 (1143 +/- 244). T4 animals showed a smaller increase in cyclic AMP following
      ISO (1391 +/- 261). There was not a significant difference between the control
      and T4 group cyclic AMP level following ISO. Thus, despite increased beta
      adrenoceptor numbers, there was a diminished responsiveness of heart rate,
      coronary blood flow and cyclic AMP levels to isoproterenol in the T4-treated
      rabbit hearts.

PMID- 8263964
TI  - Protective effects of the potent Na/H exchange inhibitor methylisobutyl amiloride
      against post-ischemic contractile dysfunction in rat and guinea-pig hearts.
AB  - We studied the effects of the potent Na/H exchange inhibitor methylisobutyl
      amiloride (MIA, 1 microM) on post-ischemic ventricular recovery and energy
      metabolic status in spontaneously contracting, isolated rat and guinea-pig hearts
      subjected to 45 min zero-flow ischemia followed by reperfusion. For both species,
      MIA was added either 15 min prior to ischemia and was present throughout
      reperfusion or was added at the time of reperfusion only. In control rat hearts,
      force recovery after 30 min of reperfusion was 25.6 +/- 6.0% of the pre-ischemic
      value whereas in hearts pre-treated with MIA recovery was enhanced to 55.4 +/- 9%
      (P < 0.05). Elevation of resting tension during the first 20 min of reperfusion
      was also significantly reduced by MIA pre-treatment. When MIA was added at the
      time of reperfusion only, recovery was generally lower than that seen with MIA
      pre-treatment although significantly higher values were seen through much of the
      reperfusion period. In rat hearts, MIA reduced the time required for return to
      sustained contractile recovery particularly in those hearts where the drug was
      added prior to ischemia (control, 11.4 +/- 2.7 min; MIA, 2.6 +/- 0.5 min, P <
      0.05). Similar effects of MIA pre-treatment were seen in guinea-pig hearts in
      terms of contractile recovery, time to recovery and reduction in resting tension
      although MIA addition at the time of reperfusion was without beneficial effect
      either on the magnitude of contractile recovery or time required for restoration
      of function. In guinea-pig hearts, recovery of function was accompanied by
      substantial bradycardia. However, maintenance of ventricular rate through
      electrical pacing exerted no significant influence on the protective effects of
      MIA pre-treatment. There was no effect of MIA on energy metabolites in reperfused
      rat hearts or paced guinea-pig hearts, although in spontaneously contracting
      guinea-pig hearts improved recovery of function was associated with significantly
      higher levels of high energy phosphates. No effects of tissue metabolites were
      seen in ischemic non-reperfused hearts irrespective of treatment. The protective
      effects of MIA were not related to diminished release of creatine kinase during
      reperfusion. Our results demonstrate marked protective effects of MIA, on the
      reperfused rat and guinea-pig myocardium. These studies also demonstrate, for the
      first time, that the effects of amiloride analogues are not species specific and
      further support the concept that Na/H exchange inhibition may represent an
      effective therapeutic approach for the protection of reperfused cardiac tissue.

PMID- 8263965
TI  - Stretch-induced inositol trisphosphate and tetrakisphosphate production in rat
      cardiomyocytes.
AB  - The kinetics and signal transduction of inositol phosphate production were
      studied after a 20% stretch of neonatal rat cardiomyocytes in culture. Inositol
      trisphosphate (IP3) production was increased by 41% above control after 10-20 s
      of cellular stretch but returned to control after 120 s of stretch. The increase
      in IP3 was potentiated in high K+ medium and was inhibited by pertussis toxin,
      suggesting the existence of a pertussis toxin-sensitive G protein in signal
      transduction. Ion-pair HPLC analysis of cell extracts stretched for 20 s showed
      an increase in both IP3 isomers, mostly 1,4,5-IP3 (+66%) with a weak increase in
      IP4 (+10%), whereas 120 s stretch induced an increase in IP4 (+26% above control)
      associated with a decrease of 1,4,5-IP3 isomer as compared with 20 s stretch. It
      is concluded that the progressive increase in IP4 production associated with an
      early rise in IP3 after stretching myocardial cells may be a factor inducing the
      length-dependent activation of cardiac muscle through a modulation of
      intracellular free calcium concentration.

PMID- 8263966
TI  - Neuron-oligodendroglial interactions during central nervous system development.
AB  - It is well established that a variety of growth factors influence the
      differentiation of oligodendroglial lineage cells in culture, although little
      information is available concerning the role and source of these factors in vivo.
      Developing oligodendroglia are almost constantly in a neuronal environment and
      would be expected to respond to a variety of signals from neurons that affect
      their survival, migration, division, maturation and myelin production. However,
      very little is known about the specific interactions that occur between these two
      cell types. Here we review the experimental evidence for the influence of neurons
      on oligodendroglial differentiation, including studies on the effects of both
      soluble factors and contact dependent events. We also propose a scheme for the
      control of myelinogenesis via both internal and external signals.

PMID- 8263967
TI  - Possible role of myelin-associated neuraminidase in membrane adhesion.
AB  - Previous studies from our laboratory have demonstrated the presence of a specific
      interaction between myelin-associated neuraminidase and GM1 (Saito and Yu, J
      Neurochem 47:632-641, 1986). In the present study, we further characterized this
      neuraminidase-GM1 interaction and examined its role in the adhesion of rat
      oligodendroglial cells to GM1. Hydrolysis of N-acetylneuramin-lactitol by the
      enzyme was inhibited by GM1 in a competitive manner; GM1 itself was not
      hydrolyzed, suggesting that GM1 may serve as a competitive inhibitor of the
      enzyme. Asialo-GM1 had no inhibitory effect. When a soluble enzyme preparation
      was applied to a GM1-linked affinity column, the enzyme activity was retained on
      the column and was recovered from the column only by elution with a buffer
      containing 5 mM 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (Neu2en5Ac), a
      competitive inhibitor of neuraminidase. A binding study with 51Cr-labeled rat
      oligodendroglial cells showed that oligodendroglial cells bound preferentially to
      GM1 developed on a thin-layer plate, but not to other gangliosides such as GM3,
      GD1a, GD1b, and GT1b. The binding reaction to GM1 was inhibited by Neu2en5Ac (5
      mM). These results suggest that myelin-associated neuraminidase specifically
      interacts with GM1 and may be involved in adhesion of oligodendroglial cells to
      GM1. This neuraminidase-GM1 interaction may play an important role in the
      formation and stabilization of the multilamellar structure of the myelin sheath.

PMID- 8263968
TI  - Expression of neuromodulin (GAP-43) and its regulation by basic fibroblast growth
      factor during the differentiation of O-2A progenitor cells.
AB  - In a recent work we have shown that neuromodulin (Nm, also known as GAP-43), a
      protein kinase C substrate, previously believed to be expressed exclusively in
      neurons, is also present in glial cells. Here we investigated the expression of
      Nm and its mRNA in O-2A glial progenitor cells (common precursor for
      oligodendrocytes and type-2 astrocytes) during their development in secondary
      culture and under the influence of basic fibroblast growth factor (bFGF). The
      different stages of oligodendrocyte development were characterized by the
      expression of surface markers: A2B5, which identifies O-2A glial precursor cells,
      and O4 and galactocerebroside (GC), which characterize later developmental
      stages. The number of cells expressing Nm (about 90% at culture initiation)
      decreased rapidly during the first 2 days and reached a plateau at around 30-40%.
      The level of Nm mRNA followed a similar kinetic. Immunocytochemistry demonstrated
      that at 4 days in vitro about 25-30% cells were A2B5+, 30-40% Nm+, a high
      percentage (60-70%) O4+, and 35-40% GC+. Nearly all of the morphologically
      immature A2B5+ cells expressed also the Nm antigen, very few of the O4+ cells
      still expressed Nm and almost no cells expressed both GC and Nm. Most O4+ cells
      developed a typical oligodendrocyte morphology and were essentially GC+. This
      study also showed that in the presence of serum, the A2B5+ Nm+ and O4+ Nm+ (GC-)
      cells retained their bipotentiality and differentiated into GFAP+ (glial
      fibrillary acidic protein) Nm+ type-2 astrocytes. The bFGF was found to stimulate
      the proliferation of Nm+ 0-2A precursor cells and to increase the level of Nm
      mRNA. At 4 days under this culture condition, the predominant cell type was A2B5+
      and Nm+. Only 25-35% of the cells were O4+, but 90-95% of them were Nm+. Very few
      GC+ cells were visible in the presence of bFGF, but 20-40% of them were Nm+.
      These data indicate that Nm is essentially associated to glial O-2A precursor
      cells and further confirm that bFGF blocks the differentiation of these cells. It
      is suggested that Nm plays a role in the plasticity (developmental potential) of
      the bipotential 0-2A progenitor cells.

PMID- 8263969
TI  - Phosphorylation and disruption of intermediate filament proteins in
      oligodendrocyte precursor cultures treated with calyculin A.
AB  - Treatment of primary cultures of oligodendrocyte precursors with calyculin A, a
      potent inhibitor of protein phosphatases 1 and 2A, caused the phosphorylation of
      two intermediate filament components, nestin and vimentin. Phosphoamino acid
      analysis demonstrated that phosphorylation took place mainly on serine and to a
      lesser extent on threonine residues. In addition, calyculin A treatment caused a
      shift in the distribution of the two proteins from the Triton-X-100 insoluble
      fraction to the detergent soluble fraction as demonstrated by immunoblotting.
      This redistribution, which was evident within 15 min after treatment and was
      nearly completed by 90 min, was accompanied by a disruption of the intermediate
      filament network. Thus, both nestin and vimentin retracted from the cytoplasmic
      processes to form a large perikaryal ring as shown by immunocytochemical
      analysis. Both morphological and biochemical changes were reversed 2-5 hr after
      removal of calyculin A from the culture medium.

PMID- 8263970
TI  - Microtubule-associated protein 2 appears in axons of cultured dorsal root ganglia
      and spinal cord neurons after rotavirus infection.
AB  - The immunohistochemical distribution of microtubule-associated protein 2 (MAP2),
      being normally restricted to nerve cell bodies and dendrites, became altered in
      rat dorsal root ganglia and spinal cord neurons in cultures infected with rhesus
      rotavirus. MAP2 appeared in axons of both sources of neurons as displayed with
      monoclonal antibodies to MAP2a + b and MAP2a + b + c at 48 hr post-infection
      (p.i.). Other cytoskeletal elements, i.e., tau, MAP1, MAP5, neurofilament, actin,
      and tubulin, did not reveal any alterations in the rotavirus-infected neurons.
      One of the rotavirus cytosolic proteins, the inner capsid protein vp6, was
      expressed in axons at 48 hr p.i. simultaneously with the appearance of MAP2,
      while two other viral proteins, vp4 and NS28, remained in the nerve cell bodies.
      By quantitative enzyme-linked immunosorbent assay (ELISA) a binding of single
      shelled rotaviruses, which express vp6 on their surfaces, to purified MAP2 was
      found. There was no binding of these viral particles to tau or tubulin proteins.
      This study indicates that a selective interaction between certain viral and
      neuronal cytoskeletal proteins can occur and that a non-cytolytic viral infection
      can cause alterations in the polarized sorting of neuronal proteins.

PMID- 8263971
TI  - Atypical localization of the oligodendrocytic isoform (PI) of glutathione-S
      transferase in astrocytes during cuprizone intoxication.
AB  - Immunocytochemical staining for the Pi and Mu isoforms of glutathione-S
      transferase was used to investigate changes in the glial cells in the mouse
      forebrain. During early development in mouse forebrains the localizations of
      carbonic anhydrase, Pi and Mu were similar to the respective cellular
      localizations that had been observed in neonatal rat brain. That is, Pi was found
      in oligodendrocyte precursors, Mu in astrocytes, and carbonic anhydrase in both
      oligodendrocyte precursors and astrocytes. In forebrains of 6-week-old mice the
      neurotoxicant, cuprizone, induced oligodendrocyte degeneration, gliosis, and
      partial demyelination. Degeneration, gliosis, and partial demyelination.
      Degeneration of oligodendrocytes, and astrocytosis, began during the initial week
      of cuprizone feeding, and by the end of the eighth week some demyelination was
      observed. After mice were fed cuprizone for 4 to 7 weeks, Pi appeared in some of
      the reactive astrocytes, and Pi-positive astrocytes were present for at least 7
      additional weeks. Normally, Pi appeared only in oligodendrocytes. Very few Pi
      positive oligodendrocytes remained after the second week. During the eighth week
      healthy-looking carbonic anhydrase-positive oligodendrocytes reappeared and began
      to accumulate, and a few small patches of Pi-positive oligodendrocytes were also
      observed. In summary, some novel findings about glial cells were the observation
      of an enzyme (Pi) that is lost earlier from oligodendrocytes than is carbonic
      anhydrase, the apparently unique shift in Pi expression from oligodendrocytes to
      astrocytes and the greater temporal dissociation between loss of oligodendrocytes
      and demyelination in the older mice.

PMID- 8263972
TI  - Cell blotting and isoelectric focusing of neuroblastoma-derived heparin-binding
      neurotrophic activities: detection of basic fibroblast growth factor protein and
      mRNA.
AB  - Neuroblastoma cells have been shown to contain growth factors, which may be
      involved in the regulation of cell proliferation and/or differentiation. We have
      examined whether human IMR-32 neuroblastoma cells store factors with a capacity
      to promote neuron survival and differentiation. Heparin affinity chromatography,
      cell blotting, and isoelectric focusing of IMR-32 cell extracts revealed multiple
      neurotrophic activities at molecular weights of 16.8, 24.1, 39.0, 45.3, 52.3 and
      isoelectric points of 4.0, 5.0, 8.3, 9.0. Immunocytochemistry, immunoblotting,
      and radio-immunoassay with specific antibodies suggests that one neurotrophic
      activity is immunologically identical with basic fibroblast growth factor (bFGF).
      This assumption is supported by Northern blot analysis, which shows a 6.0 kb bFGF
      transcript.

PMID- 8263973
TI  - Cell type- and differentiation-dependent expression from the mouse acetylcholine
      receptor epsilon-subunit promoter.
AB  - The nicotinic acetylcholine receptor (AChR) in adult skeletal muscle is composed
      of alpha-, beta-, epsilon-, and delta-subunits and is localized at the
      neuromuscular junction; in contrast, the more diffusely distributed fetal form is
      composed of alpha-, beta-, gamma-, and delta-subunits. To define sequences
      necessary for the transcriptional regulation of the mouse epsilon-subunit gene,
      we sequenced and analyzed 1036 bp upstream of the transcription start site. Using
      deletion analysis of the 5'-flanking region linked to the bacterial
      chloramphenicol acetyltransferase (CAT) gene and transfection of the resulting
      constructs into established cell lines, we demonstrate that a 151 bp fragment
      exhibits cell type- and differentiation-specific promoter activity. This activity
      was independent of a myogenic factor putative binding site (E-box). However,
      transactivation experiments with recombinant myoD, myogenin, or MRF4 showed that
      the E-box was functional and that MRF4 preferentially transactivates the epsilon
      promoter. Thus, like other AChR promoters, the proximal region of the epsilon
      promoter contains information for cell type-specific and developmental regulation
      of CAT and can be transactivated by myogenic factors in cultured cell lines.
      Unlike the other AChR promoters characterized to date, epsilon-promoter function
      can be partially independent of myogenic factors of the helix-loop-helix class.

PMID- 8263974
TI  - Culture model for the study of cerebral malaria: antibodies from Plasmodium
      falciparum-infected comatose patients inhibit the dendritic development of
      Purkinje cells.
AB  - The in vitro development of kitten Purkinje cells was inhibited by sera or IgG
      from cerebral malaria (CM) patients but not by sera from acute non-complicated
      malaria (NCM) cases. This inhibitory effect, quantified by computer-assisted
      methods, concerned the dendritic (though not the axonal) development and was
      found to be related to the presence of CM sera of self-reactive antibodies of the
      IgG class. These results suggest that protection acquired against the major
      complication of Plasmodium falciparum malaria may correspond to the repression of
      an abnormal stimulation of autoreactive B cells.

PMID- 8263975
TI  - Elemental diet-induced bacterial translocation and immunosuppression is not
      reversed by glutamine.
AB  - Previously, we documented that bacterial translocation occurs in rats fed an
      elemental liquid diet (4.25% amino acids plus 28% glucose) for 7 days. Since
      controversy exists over the protective effect of glutamine on diet-induced
      bacterial translocation, we compared the effect of two elemental diets, one
      containing 0% and the other 30% of amino acids as glutamine. After 7 days on the
      test diets or chow (307 kcal/kg/day), the rats were killed and half the animals
      had their organs cultured for translocating bacteria; immune function was
      quantitated in the other half by measuring the blood, splenic, and mesenteric
      lymph node (MLN) blastogenic responses to the T-cell mitogens phytohemagglutinin
      (PHA) and concanavalin A (ConA). The incidence of bacterial translocation was
      higher in the rats fed the glutamine (88%) or nonglutamine (75%) elemental diets
      than in the chow-fed rats (13%) (p < 0.05). Both elemental diets equally reduced
      the blastogenic response of lymphocytes harvested from all three lymphoid
      compartments (blood, spleen, MLN) (p < 0.01 vs. chow). The percentage of
      reduction averaged 30% to 40% when PHA was used as the test mitogen and 50% to
      70% when ConA was used. These results indicate that glutamine does not prevent
      elemental diet-induced bacterial translocation or immune suppression.

PMID- 8263976
TI  - Plasma endothelin level changes during hemorrhagic shock.
AB  - The purpose of this study was to analyze changes in plasma endothelin-1 levels
      during hemorrhagic shock. Thirty-two mongrel dogs were divided into four equal
      groups with group I as the controls and groups II through IV as experimental
      groups. The dogs in the experimental groups underwent hemorrhagic procedures. The
      mean blood pressure was kept at the level of 65 mm Hg in group II, 50 mm Hg in
      group III, and 40 mm Hg in group IV. Blood samples were collected from each dog
      under the following conditions: (1) after induction of anesthesia, when the
      animals were hemodynamically stable, before the start of shock; (2) 1 minute
      after the mean arterial pressure dropped to the level designed for each group
      (shock 1); (3) 15 minutes after shock 1; (4) 30 minutes after shock 1; (5) 1 hour
      after shock 1; (6) 2 hours after shock 1; (7) 4 hours after shock 1; and (8) 8
      hours after shock 1. Plasma endothelin-1 levels both in arterial and venous blood
      were analyzed in each dog. The results showed that (1) arterial endothelin-1
      concentrations were considerably lower than venous concentrations at the baseline
      level; (2) after the shock-1 point, plasma endothelin-1 concentrations increased,
      first markedly and then evenly throughout the oligemic period; (3) elevation of
      plasma endothelin-1 levels was significantly linearly correlated with the amount
      of blood loss at the time of 2 hours after shock and thereafter; (4) the
      arterial/venous ratio of plasma endothelin-1 levels during the oligemic period
      was higher than that in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8263977
TI  - Causes of increasing pericardial pressure in experimental cardiac tamponade
      induced by ventricular perforation.
AB  - It has been shown that the intravenous infusion of saline solution in a dog with
      stabilized cardiac tamponade produced an increase in pericardial pressure. To
      demonstrate that this pressure increase is the result of bleeding into the
      pericardial sac, an experimental study was conducted, consisting of the injection
      of red cells marked with 51Cr during the intravenous infusion of saline solution
      in dogs with and without progressive tamponade. The results showed that in the
      dogs without progressive tamponade, both the pericardial pressure and the red
      cell count in the pericardial cavity remained stable during the infusion of
      saline solution, whereas in dogs with progressive tamponade, the numbers of
      marked cells and the pericardial pressure increased significantly, following a
      similar pattern.

PMID- 8263978
TI  - Recovery following ischemic myelopathy.
AB  - Motor and sensory recovery were determined in five patients with ischemic
      myelopathy associated with traumatic laceration or surgical manipulation of the
      thoracic aorta. The neurologic level of injury was between T-2 and T-10. All
      patients had an anterior spinal artery pattern of incomplete spinal cord injury
      consisting of relatively greater loss of motor function than sensation and
      preservation of sacral sensation. None of the three patients with zero lower
      extremity motor function at 30 regained any motor function at 1 year. Two
      patients with partial motor function 1 month after infarction had further motor
      recovery at 1 year. One of these two individuals was able to ambulate
      independently with a reciprocal gait using orthoses.

PMID- 8263979
TI  - Patterns of fracture after air bag deployment.
AB  - The airbag restraint system has been described as a means of reducing fatalities
      in frontal crashes. This conclusion is based on crash investigations and
      statistical extrapolation, but few data exist to document specific fracture
      patterns and injuries after airbag deployment. Seven cases of driver's side
      airbag deployment after motor vehicle crashes were studied for extent of injury.
      Unrestrained (non-seatbelted) drivers demonstrated flexion injuries of the
      cervical and thoracic spine and direct impaction fractures of the face and
      sternum. One restrained (lap-shoulder belt) driver demonstrated an extension
      injury of the upper cervical spine. What may emerge from further study is a
      decrease in fatalities, but also a pattern of fractures specific to airbag use.

PMID- 8263980
TI  - Lymphocyte subset responses to trauma and sepsis.
AB  - One hundred five trauma patients admitted to three trauma centers with injury
      Severity Scores of 20 or greater had lymphocyte phenotypic subsets characterized
      throughout their hospital course. Total lymphocytes, pan-T (CD2), helper T (CD4),
      suppressor T (CD8), pan B (CD20), and DR expressing lymphocytes were quantitated
      by monoclonal antibodies and flow cytometric analysis. Results were analyzed
      between three patient groups: uninfected, uneventful recovery (n = 64); major
      infection (n = 26); and dead (n = 15; 7 with sepsis). A significant lymphopenia,
      maximal at 3 days, occurred in the first postinjury week compared with controls
      (p < 0.05), which recovered over the study period. A hierarchical distribution
      was found between the three outcome groups with the lowest numbers of several
      lymphocyte phenotypes in those who died. T helper and suppressor cells were
      similarly affected, but lowest in patients destined to develop infection or die.
      The helper-suppressor ratio, however, was similar in all three outcome groups.
      Therefore, modulation early after injury aimed at restoring these subsets may
      reduce the risk of subsequent infection.

PMID- 8263981
TI  - Randomized trial comparing cryopreserved cultured epidermal allografts with tulle
      gras in the treatment of split-thickness skin graft donor sites.
AB  - Cultured epidermal allografts have been successfully used to treat a wide variety
      of skin defects ranging from burns to leg ulcers. Their postulated mechanism of
      action is through release of multiple cytokines that stimulate epithelialization
      from the wound periphery as well as from remnant epidermal appendages. A
      randomized, controlled clinical trial was undertaken to compare the efficacy of
      cryopreserved cultured allograft dressings (CCAD) with tulle-gras dressings in
      the treatment of split-skin graft donor sites. Five patients were enrolled in the
      study and in each patient, half of the donor site was allografted and the other
      half was treated with tulle-gras control. The mean time to complete healing was
      6.2 days for CCAD compared with 9.6 days (p = 0.035) for the tulle-gras controls.
      Patient assessment of pain with dressing changes was also significantly lower at
      the CCAD-treated sites than at the control sites (p = 0.001). The results
      indicate that cultured allografts offer greater patient comfort and earlier
      maturation of regenerated skin.

PMID- 8263982
TI  - Traumatic intracranial aneurysms: a contemporary review.
AB  - Intracranial aneurysms are rare complications of head injury. Clinical and
      pathologic features as well as the surgical treatment of patients harboring
      traumatic intracranial aneurysms are presented. The latest neuroradiologic
      procedures as they relate to traumatic aneurysms are discussed. An illustrative
      case report is followed by a review of the literature.

PMID- 8263983
TI  - Renal artery occlusion in pediatric blunt abdominal trauma--decreasing the delay
      from injury to treatment.
AB  - The cases of seven children treated from 1980 through 1991 with blunt renal
      artery injuries were reviewed to determine (1) if computed tomography alone could
      eliminate the need for intravenous pyelography (IVP) or arteriography (ART); and
      (2) the causes of management delays. The diagnosis of arterial occlusion was
      suggested by the lack of renal contrast enhancement in six patients with CT scans
      and in two patients with IVP. In three patients ART was merely confirmatory. The
      diagnosis was suggested by IVP or CT scan within a mean of 4.7 hours of injury,
      but ART added an additional mean 2.3 hours to the diagnostic workup. There was an
      additional 3.9-hour average delay in the operating room before revascularization.
      Six patients underwent revascularization. Four had minimal function by
      postoperative renal scans. Renal artery occlusion is rapidly detected by contrast
      enhanced CT scanning without IVP or ART. The time period from diagnosis to
      revascularization must be expedited to improve renal outcome.

PMID- 8263984
TI  - Severe blunt trauma of the liver: study of mortality factors.
AB  - One hundred three victims of blunt trauma of the liver with serious hepatic
      lesions (classes III through V of Moore's classification) were seen over a period
      of 18 years, the total duration of this retrospective study being divided in two:
      1973-1981 and 1982-1990. During the first period, indications for hepatic
      resection were extensive (56% of all surgical procedures), and overall
      perioperative mortality was 24%. Preference was shown for conservative treatment
      during the second period (71% of patients) and there was an increase in
      perioperative mortality to 34%. This increase was not attributable to the
      decrease in the number of excisions but rather to an increase in the severity of
      hepatic lesions between the two periods (the rate of class V lesions rising from
      17% to 26% of cases) and the rate of multiple trauma (rising from 41% to 95%),
      with mortality linked to the presence of extra-abdominal lesions rising from 20%
      to 50% of all deaths. These results may bring into question the validity of
      conservative treatment for liver trauma at the present time.

PMID- 8263985
TI  - Adrenal gland trauma: diagnosis and management.
AB  - We describe 14 patients with adrenal injuries from penetrating (ten) or blunt
      (four) trauma. The severity of their injuries was evidenced by the high incidence
      of hypovolemic shock (57%), mean Trauma Score (11), mean transfusion requirement
      (18 Units), number of associated injuries (4.9 per patient), complication rate
      (57%), and deaths (14%). Twelve patients required surgical exploration; adrenal
      repair, rather than removal, was possible in seven. Although adrenal
      insufficiency was suspected in three patients, it was not documented and no
      patient required corticosteroid replacement.

PMID- 8263986
TI  - The role of arteriography in assessing vascular injuries associated with
      dislocations of the knee.
AB  - All patients with a diagnosis of knee dislocation during a 7 1/2-year period
      (1984-1991) were reviewed retrospectively. There were 37 knee dislocations (KDs)
      in 35 patients. The mechanism of injury was predominantly motor vehicle or
      pedestrian crashes. Popliteal artery injury was present in 6 of 37 (16%). There
      was no significant vascular injury in 31 of 37 knee dislocations as evidenced by
      normal arteriograms or absence of vascular complications on follow-up. Of those
      with no significant vascular injury, 3 of 31 had limb ischemia that improved with
      reduction of the KD, had normal arteriograms, and had no further vascular
      treatment. All patients with popliteal artery injury had a pulse deficit (five of
      six) or a documented history of ischemia (six of six). In the absence of these
      findings, no patient was found to have an arterial injury. Arterial injuries were
      treated with interposition (five of six) or bypass graft (one of six) and
      fasciotomies (six of six). Amputation was required in one of six of the vascular
      injury group and none of 31 of the remainder of the patients with no vascular
      injury. We recommend the selective use of arteriography in patients with KDs
      based on a history or clinical findings of ischemia and do not recommend routine
      arteriography for all patients with KD.

PMID- 8263987
TI  - The interosseous membrane of the forearm: structure and its role in Galeazzi
      fractures.
AB  - A cadaveric study was performed to anatomically describe and mechanically
      document the interosseous membrane of the forearm using gross, histologic,
      scanning electron microscopic, and mechanical testing. The membrane was found to
      be a complex structure composed of nerves and vessels but mainly of collagen
      fibers that thicken to form bands coursing from radius to ulna. Strain-gauge
      studies demonstrated that the load transfer occurs from the radius to the ulna
      via the membrane and changes with supination or pronation. With specimens under a
      specific test load, sectioning of the membrane allowed the fractured radius to
      shorten by 6.25 mm and sectioning of the triangular fibrocartilage complex
      resulted in shortening of 7.7 mm. Total shortening after osteotomy and sectioning
      of the complex structure and membrane ranged from 15 to 40 mm. In Galeazzi
      fractures, the interosseous membrane acts as a constraint to radial shortening.
      Anatomic reduction with internal fixation is indicated for this fracture
      dislocation.

PMID- 8263988
TI  - The lateral atlanto-axial joints and their synovial folds: an in vitro study of
      soft tissue injuries and fractures.
AB  - Thirty victims of blunt cervical trauma, who did not survive (acute death group),
      were studied at autopsy as were 11 patients who survived trauma for more than 1
      month and ten controls without any known cervical trauma. All specimens were
      sagitally sectioned in 2-mm slices and carefully examined for injuries to the
      lateral parts of the atlanto-axial joints. In the acute death group, five cases
      showed a rupture of the joint capsule, three of these with a massive
      hemarthrosis. In 17 cases there was bruising around the second cervical spinal
      nerve. Bruising of the intra-articular synovial fold was present in 15 cases, the
      posterior synovial fold being most commonly affected. There were five intra
      articular fractures of the lateral masses, in three cases combined with a dens
      fracture. In two cases a bone fragment from the fracture compressed and
      obliterated the lumen of the vertebral artery. The findings are discussed in
      relation to pain after cervical trauma.

PMID- 8263989
TI  - A crook plate for treatment of acromioclavicular joint separation: indication,
      technique, and results after one year.
AB  - From 1987 through 1991 thirty-five patients underwent surgical repairs with
      Wolter's crook plates for acromioclavicular joint rupture. Sixteen of the
      patients had Post type IV lesions: another 19 patients had the same procedure for
      Tossy type III lesions. Active shoulder motion up to 90 degrees of abduction and
      forward flexion was allowed 48 hours postoperatively. All but one patient
      regained full range of motion at 8 weeks. Precise bending of the plate before
      insertion and an accurate drill hole for the crook in the acromion were essential
      to prevent impingement and also precluded ventral or cranial subluxation in the
      joint. Using the shoulder evaluation method proposed by Constant and Murley,
      after 1 year 94.28% (33 of 35) of the patients had excellent results.

PMID- 8263990
TI  - Correction osteotomies of phalanges and metacarpals for rotational and angular
      malunion: a long-term follow-up and a review of the literature.
AB  - Correction osteotomies of nine phalanges and six metacarpals for rotational and
      angular malunion were performed in 15 patients ranging from 20 to 75 years of age
      and followed a mean period of 4.5 years, ranging from 1 to 11 years. Full
      correction of the preoperative deformity was achieved in 13 of the 15 patients
      (87%), bony union in 100%, and no loss of preoperative range of motion was
      observed, except in one patient who underwent additional arthrodesis. A high
      satisfaction rate was seen among 13 of the 15 patients. These results underline
      that osteotomies of phalanges and metacarpals for angular and rotational malunion
      can have significant functional benefits for the well-being of patients.

PMID- 8263991
TI  - A scheme for describing injury events.
AB  - OBJECTIVE: To develop a data collection system that provides a more comprehensive
      picture of the components of the preinjury and injury phases of injury events
      than is usually available in medical records. METHOD: Based on a scheme
      originally designed for study of occupational injuries among off-shore petroleum
      drilling workers, eight data areas were designated and lists of categories were
      developed to permit applicability to a general injury surveillance program.
      Medical records for 1600 injured patients treated at the Medical Center Hospital
      of Vermont were reviewed to determine current frequency of recording such
      information. RESULTS: A scheme for injury surveillance was designed that included
      location of the event, general and specific activities at time of injury, work
      relationship, nature of the event, animal or person contact, products or
      materials being used and those causing injury, and energy type and mechanism.
      CONCLUSION: An acceptable scheme has been developed that can be used for general
      surveillance, or modified to focus in greater detail on specific environments,
      products, or event types.

PMID- 8263992
TI  - Causes and costs of injuries in multiple trauma patients requiring extrication
      from motor vehicle crashes.
AB  - Prospective and contemporaneous medical and economic cost studies of 144 victims
      of motor vehicle crashes admitted to a regional level I trauma center with
      multiple injuries (ISS > or = 16) revealed 122 non-ejected patients, of whom 102
      required extrication (EXTRIC) from the vehicle for physical or medical reasons
      and 20 who did not (N group). There were no differences in age (EXTRIC, 34 +/- 17
      years; N, 41 +/- 24 years), type of crash (Frontal: 57% EXTRIC, 60% N; Lateral:
      32% EXTRIC, 35% N) restraint use (35% EXTRIC, 35% N), or mortality (29% EXTRIC,
      30% N). However, the estimated maximum speed before the crash was higher in
      EXTRIC patients (50 +/- 16 mph vs. 46 +/- 18 mph N, p < 0.04), as was the change
      in velocity (delta V) on impact (EXTRIC 30 +/- 15 mph; N, 24 +/- 8 mph, p <
      0.01). Brain injuries (51% EXTRIC vs. 35% N) and lower extremity injuries were
      more numerous in EXTRIC patients (59% vs. 20% N, p < 0.003) and the number of
      splenic, lower extremity, and pelvic injuries associated with shock was greater
      in EXTRIC patients, p < 0.02; as were postinjury complications. As a result,
      operating room costs from orthopedic and plastic surgery increased professional
      charges in the EXTRIC group versus the N group ($20,000, EXTRIC; $17,000, N) and
      critical care costs ($13,000, EXTRIC; $4,000, N) with total costs of $72,000 and
      $77,000, respectively. The lower extremity injuries in EXTRIC patients were
      primarily a result of body part contacts with intrusions (CIs) of the car
      occupant compartment structures [73% with vs. 24% without (p < 0.0001)]. In
      lateral MVCs, brain injuries were also more commonly associated with CIs of the
      side window frame or A pillar (72% CI vs. 25% no CI; p < 0.035); but as a whole
      in MVCs in which extrication was necessary, lower extremity injuries from
      instrument panel or toepan CIs appeared more frequent than those resulting from
      contacts only (p < 0.0001). In EXTRIC patients, 69% of those in shock had CI
      injuries, and 80% of the deaths in the EXTRIC group were associated with CI
      injury. These data suggest that measures designed to prevent CIs by strengthening
      car passenger compartment structures may reduce the incidence of severe brain and
      lower extremity injuries and may reduce the need for extrication after MVCs.

PMID- 8263993
TI  - Quantitation of impact attenuation of different playground surfaces under various
      environmental conditions using a tri-axial accelerometer.
AB  - OBJECTIVE: To rank playground surfaces with respect to impact attenuation under
      various simulated environmental conditions. DESIGN: An accelerometer was dropped
      from a height of 60 inches onto five different playground surfaces (wood chips,
      sand, gravel, grass, and commercial rubber mats). Impact attenuation was measured
      (in G forces) with the above surfaces dry, wet, and frozen. INTERVENTIONS: The
      accelerometer was dropped ten times onto each surface. All surfaces were tested
      in the wet, dry, and frozen states (saturated with water, then placed at -10
      degrees C for 12 hours). RESULTS: Analysis of variance revealed that wood chips
      significantly lowered impact forces compared with sand in the wet or dry
      condition and to grass or synthetic mats in the dry or frozen condition (p <
      0.05). Wood chips absorbed the shock of impact significantly more than did gravel
      in the dry, frozen state. CONCLUSION: Wood chips appear to be the single best
      playground surface under a variety of environmental conditions when assessed by
      impact attenuation studies.

PMID- 8263994
TI  - Impact resistance of bar glasses.
AB  - Bar glasses are often used as weapons in interpersonal violence. Violence often
      erupts spontaneously and assailants use objects close to hand as weapons. After
      an initial national Accident and Emergency Department study to identify glass
      designs most often implicated in interpersonal violence, the impact resistance of
      1-pint beer glasses was tested in a materials laboratory with a Zwick 5102
      pendulum impact tester. Both straight-sided (nonik) glasses (annealed and
      tempered) and handled tankards (annealed) were tested to destruction. The impact
      resistance of new glasses was compared with that of glasses subjected to wear.
      The mean impact resistance of new annealed noniks did not differ significantly
      although new glasses were significantly more resistant than worn glasses (p <
      0.01). It was not possible to break any of the tempered glasses with the pendulum
      used (maximum impact energy, 4 J). When noniks had been scratched at the rim to
      mimic wear, tempered glasses also had the highest impact resistance (p < 0.01)
      whereas the mean resistance of the annealed noniks was not significantly
      different. When tempered glasses failed during testing, they all disintegrated
      into relatively harmless cubes of glass, particularly the thicker bases of
      glasses. In contrast, annealed designs fractured leaving sharp shards although
      the thicker bases remained intact. The mean impact resistance of new annealed
      noniks was 0.5 J, of worn annealed noniks 0.08 J, of tempered new noniks > 4 J,
      of worn tempered noniks 0.18 J, and of tankards, 1.7 J.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8263995
TI  - Fractures of the mandible caused by stoning--return of an ancient entity.
AB  - Fifteen patients with mandibular fractures related to stone-throwing incidents
      are presented. Three illustrative cases are discussed in detail. Criteria for
      selecting management by early surgical intervention or a conservative approach
      are discussed. The ultimate aim in management is to preserve the greatest
      possible amount of function with the least risk and morbidity for the patients.

PMID- 8263996
TI  - Nail gun injuries.
AB  - The nail gun is a potentially dangerous device that is commonly used in the
      construction industry to drive various sizes of nails into wood or concrete.
      These devices appear to be used without sufficient training and they can be
      easily obtained by the general public. We report a series of injuries caused by
      nail guns. The pattern of these injuries and the mechanism of their production
      suggest that the safety mechanisms on the guns and the protective clothing worn
      by operators of the guns do not prevent injuries. We call for a review of
      operator training and the design of both the safety mechanism of nail guns and
      the protective clothing worn by operators. If necessary, modifications should be
      introduced to reduce the likelihood and severity of such potentially serious
      injuries.

PMID- 8263997
TI  - Wheels-in-line roller skating injuries.
AB  - Injuries sustained by patients using wheels-in-line roller skates were reviewed
      in a survey of 57 cases collected by the Roosevelt Hospital Hand Service and 444
      cases compiled by the Consumer Product Safety Commission. Most patients were
      novice skaters in the second and third decades of life. Severe distal radius
      fractures and upper extremity soft-tissue trauma were the most common injuries in
      both groups. The distal radius (44.9%), scaphoid (13.9%), and radial head (10.4%)
      were the three most common fracture sites in the Roosevelt survey. Most (80%)
      skaters in this group did not wear protective equipment. In-line roller skating
      can and does produce disabling injuries. Also, several deaths were reported among
      skaters traveling in heavy traffic. To reduce the number of injuries, all skaters
      should wear protective gear, especially wrist and elbow pads. Splints reduce but
      do not eliminate the potential for trauma. In our study most injured skaters had
      not mastered controlled skating and stopping techniques. This new recreational
      sport is increasing in popularity and more injuries are expected if skaters fail
      to protect themselves properly.

PMID- 8263998
TI  - Laparoscopic retrieval of a migrating intrapelvic pin: case report and review of
      the literature.
AB  - Migration of orthopedic implants is a well documented phenomenon. Prompt
      recognition and immediate retrieval may prevent significant and potentially fatal
      sequelae. The following report describes a unique case in which laparoscopic
      techniques were successfully used to recover a migrating intrapelvic pin.

PMID- 8264000
TI  - Ipsilateral radial head dislocation with radial shaft fracture: case report.
AB  - An extremely rare injury, traumatic radial head dislocation with concomitant
      fracture of the radial shaft, is reported. The dislocated radial head could not
      be reduced by closed technique because of capsular interposition. Reduction of
      the radial shaft fracture was possible only after the dislocation of the radial
      head was reduced.

PMID- 8263999
TI  - Reno-colic fistula following primary repair of the colon: case report.
AB  - Reno-colic fistula is a rare entity that to our knowledge has not previously been
      reported as a complication of penetrating abdominal trauma. We report a case of
      reno-colic fistula complicating primary repair of a colonic wound from a gunshot
      to the abdomen. Causes of previously reported reno-colic fistulas include primary
      renal and colonic pathologic states involving infectious, malignant, or other
      inflammatory processes. The occurrence of this complication may have been related
      to the primary repair of the colon. Although recent reports support primary
      colonic repair, perhaps renal injuries deserve special consideration when
      patients are evaluated for primary versus staged repair of penetrating colon
      injuries.

PMID- 8264001
TI  - Traumatic incarceration of the small bowel: case report.
AB  - While bowel injuries associated with blunt abdominal trauma are a well recognized
      entity, entrapment of bowel between vertebral bodies has seldom been described.
      The unusual case of traumatic jejunal incarceration between two lumbar vertebrae
      is presented.

PMID- 8264002
TI  - Unreduced dislocation of the elbow: case report and review of the literature.
AB  - A case report of an unreduced dislocation of the elbow requiring late open
      reduction is presented, and the literature is reviewed. Early reduction of elbow
      dislocation, by closed or open means, is of paramount importance if good
      functional results are to be obtained. Closed reduction of an elbow dislocation
      is unlikely to be successful if attempted later than 21 days after the injury.
      The results are acceptable if open reduction is undertaken within 3 months of the
      injury, but after 6 months the results are disappointing and arthroplasty is an
      alternative.

PMID- 8264003
TI  - Traumatic pseudoaneurysm of the supra-orbital artery associated with von
      Willebrand's disease: case report.
AB  - The presence of an established coagulation disorder, in conjunction with minor
      arterial trauma, may lead to the genesis of a pseudoaneurysm. We report a case of
      a traumatic pseudoaneurysm of the supraorbital artery after minor blunt trauma in
      a patient with von Willebrand's disease.

PMID- 8264004
TI  - Likelihood of the death of an infant or young child in a short fall of less than
      6 vertical feet.

PMID- 8264005
TI  - Oxygen transport (O2T) variables in the early phase following injury.

PMID- 8264006
TI  - Global Spine and Head Injury Prevention (SHIP) Project.

PMID- 8264007
TI  - Injury occurring secondary to distraction from a Sony Walkman or one of its
      clones.

PMID- 8264008
TI  - Once a trauma surgeon.

PMID- 8264009
TI  - EMSAT, Advanced Technology for Emergency Medical Services.

PMID- 8264010
TI  - On scene helicopter transport of patients with multiple injuries--comparison of a
      German and an American system.

PMID- 8264011
TI  - Gastric and duodenal wall thickening on abdominal ultrasonography. Positive
      predictive value.
AB  - In a retrospective study, 79 patients with gastric (n = 59) or duodenal (n = 20)
      wall thickening on conventional abdominal ultrasonograms were included. To reduce
      bias, patients with a microscopic diagnosis of upper GI neoplasia present at the
      time of scanning were excluded. The final diagnosis was based upon endoscopy,
      operation, upper GI series, or autopsy. Among the 59 cases of gastric wall
      thickening, 33 (56%) proved to be gastric cancer, one (2%) was benign neoplasia,
      and 17 (29%) showed nonneoplastic pathology (ulcer, gastritis, fibrosis). In
      eight cases (13%) no gastric pathology was present in the final diagnosis, thus
      producing false-positive sonographic diagnoses. Among the 20 cases of duodenal
      wall thickening, five (25%) proved to be duodenal cancer and seven (35%) showed
      nonneoplastic duodenal pathology. We concluded that gastric or duodenal wall
      thickening shown on abdominal sonography is a significant finding indicating
      upper GI pathology (malignant or nonmalignant) in a high percentage of the
      gastric (86%) and duodenal (60%) cases.

PMID- 8264012
TI  - Asymptomatic calcifications of a normal-sized ovary.

PMID- 8264013
TI  - A comparison of fetal growth curves with mathematical modeling.

PMID- 8264014
TI  - Isolated reversed umbilical arterial blood flow on Doppler ultrasonography and
      fetal hiccups.
AB  - Absent and reversed UA end-diastolic blood flow is usually a poor prognostic
      sign. However, in 19 fetuses evaluated in the Fetal Diagnosis and Treatment Unit,
      we observed an unusual pattern of intermittent, significantly decreased, or
      reversed UA blood flow that coincided with a demonstration of fetal hiccuping. No
      evidence of cardiac arrhythmia, heart failure, or uteroplacental dysfunction was
      found in these fetuses. With one exception, all Doppler evaluations were
      otherwise normal. A potential mechanism of intermittent fetal UA blood flow
      reversal is discussed.

PMID- 8264015
TI  - Fetal cardiac outflow tract screening.

PMID- 8264016
TI  - Improved prediction of gestational age in the late third trimester.
AB  - A variety of formulas have been published for predicting GA in the second and
      third trimesters. We assessed these formulas for the presence of systematic
      errors. Our study population consisted of 1036 obstetrical sonograms at 14 to 42
      weeks' gestation in patients with highly accurate dating based on a prior first
      trimester scan. Most formulas had mean errors (mean value of the difference
      between predicted and true GA) of no more than 1 week between 14 and 38 weeks'
      gestation. At 38 to 42 weeks, however, all formulas had large systematic
      underestimation biases, with mean negative errors in the range of 1.6 to 3 weeks.
      By regressing ln(GA) against one or more measurements, we developed new formulas
      that eliminate this underestimation bias, with mean errors of no more than 0.6
      week throughout the entire 14 to 42 week period. As with current formulas,
      however, our formulas have wide 95% confidence ranges of +/- 3 weeks or greater
      at 38 to 42 weeks as a result of inherent biological variability. We recommend
      the use of these formulas in clinical practice, as they may prevent errors in
      diagnosis late in pregnancy.

PMID- 8264017
TI  - Renal resistive indices in children.
AB  - We established renal vascular RIs in 177 normal kidneys in children. Age
      dependency of RIs was noted in children with normal kidneys. As compared to
      adults, renal RIs were found to be normally higher in children up to 10 years.

PMID- 8264018
TI  - Fetal echocardiography: factors that influence imaging of the fetal heart during
      the second trimester of pregnancy.
AB  - OBJECTIVE: The four-chamber view of the heart is an important component of the
      ultrasonographic examination of the fetus. However, during the second trimester
      of pregnancy the fetal heart cannot always be imaged in every patient. The
      purpose of this study was to ascertain the rate of successful imaging of the
      fetal heart during the second trimester and to determine factors that may
      influence imaging. METHODS: Seven hundred and nine second trimester fetuses were
      examined and an attempt was made to obtain the four-chamber and outflow tract
      views of the heart. Analysis included multiple logistic regression models of the
      main effects and interactions of ten candidate variables. RESULTS: The four
      chambers and outflow tracts were imaged in 643 fetuses (90.7%) and not imaged in
      66 (9.3%). Fifty-two of 709 patients (7.3%) had had previous surgery. In the 52
      patients with a history of previous surgery, the heart could not be imaged in 18
      (34%). Six hundred and fifty-seven patients (92.7%) did not have previous
      surgery. Of this group, the fetal heart could not be imaged in 48 (7.3%). In only
      one fetus in which the heart could not be imaged was it because of fetal
      position. Three independent risk factors that influenced imaging of the fetal
      heart were gestational age, maternal adipose tissue thickness, and previous lower
      abdominal surgery. Increasing gestational age increased the probability of
      imaging the heart, whereas increasing adipose tissue thickness and a history of
      previous surgery decreased the probability of imaging the heart. COMMENTS: When
      the fetal heart cannot be imaged during the second trimester, these factors
      should be identified. Using data from this study, the gestational age at which
      the highest probability of imaging the heart can be determined if the thickness
      of the adipose tissue and a history of lower abdominal surgery are known.

PMID- 8264019
TI  - Predicting pregnancy survival from a single first trimester vaginal
      ultrasonogram.
AB  - This retrospective study evaluates early first trimester FHR, gestational SACD,
      and CRL measurements as means to predict ultimate pregnancy outcome. Outcomes of
      274 pregnancies were monitored a single time by transvaginal ultrasonography with
      measurements recorded between 5.0 and 9.0 weeks' gestation. The measurements were
      then correlated with the pregnancy outcomes. FHR (P < 0.0001), gestational SACD
      (P = 0.0002), and CRL (P = 0.0059) each correlated positively with a successful
      pregnancy outcome. Measurements from a single transvaginal ultrasonogram can be
      used to predict a successful pregnancy outcome in the early first trimester.

PMID- 8264020
TI  - Simultaneous Doppler recording of the pulmonary artery and vein: a new technique
      for the evaluation of a fetal arrhythmia.
AB  - We describe a new technique to evaluate cardiac rhythm using color and pulsed
      Doppler ultrasonography to identify and record pulmonary arterial and venous
      waveforms. Fifty fetuses were examined during the second and third trimesters of
      pregnancy. Simultaneous pulsed Doppler recording of the pulmonary artery and vein
      was obtained in 100% of fetuses between 15 and 40 weeks' gestation. Atrial
      systole was identified from the pulmonary vein and was manifested by an
      interruption of venous flow. Ventricular systole was manifested by a sharp peak
      that returned toward the baseline before it continued through the duration of
      systole as a lower-velocity waveform. This technique has the following
      advantages: (1) the lung parenchyma is easily accessible, irrespective of fetal
      position; (2) the pulmonary arteries and veins are adjacent to each other as they
      enter and exit the lung, thus making it easy to simultaneously obtain Doppler
      recordings of these vessels; (3) the pulsed Doppler waveform has an appearance
      similar to an electrocardiogram.

PMID- 8264021
TI  - Thyroid nodules: evaluation with color Doppler ultrasonography.
AB  - Forty-seven patients with thyroid nodules (13 papillary carcinomas, 14 adenomas,
      and 20 adenomatous goiters) underwent color Doppler sonography with a 7.5 MHz
      transducer. Perinodular or intranodular color flow signals were depicted in 10 of
      13 papillary carcinomas, in 10 of 14 follicular adenomas, and in 14 of 20
      adenomatous goiters. No correlation existed between the presence of color signals
      and pathology, whereas the detection rate of color signals had a dependence on
      the size of the lesions. No specific flow pattern for malignancy could be found.
      Color Doppler sonography would not improve the ability to differentiate benign
      from malignant nodules significantly.

PMID- 8264022
TI  - Acquired intercostal arteriovenous fistula: color Doppler ultrasonographic
      diagnosis.

PMID- 8264023
TI  - Prenatal diagnosis of fetal cutaneous hemangioma: case report and review of the
      literature.

PMID- 8264024
TI  - Transient omphalocele.

PMID- 8264025
TI  - Fetal hemangioma overlying the temporal occipital suture, initially diagnosed by
      ultrasonography as an encephalocele.

PMID- 8264026
TI  - Pseudotumoral appearance of a duodenal diverticulum by ultrasonography: a case
      report.

PMID- 8264027
TI  - Acute afferent loop obstruction caused by retroanastomotic hernia.

PMID- 8264028
TI  - Death associated with asymptomatic carotid artery stenosis: long-term clinical
      evaluation. VA Cooperative Study 167 Group.
AB  - PURPOSE: As part of a prospective clinical trial on the efficacy of carotid
      endarterectomy in patients with asymptomatic carotid artery stenosis, we studied
      the risk factors for death in 444 male patients. METHODS: At entry to the trial,
      patients were judged to be healthy enough to be randomized to operative
      intervention and were judged to be free of any disease that would preclude a
      minimal 5-year life expectancy after randomization. RESULTS: Patients were
      treated with aspirin and optimal medical care and were monitored for an average
      of 4 years. Combined mortality rate was 37% (9% per year) for the medical group
      (38%) and surgical group (35%). Eight factors were identified that were
      significantly associated with increased mortality rates: coronary artery disease
      (p = 0.044), history of angina (p = 0.047), congestive heart failure (CHF) (p =
      0.012), abnormal electrocardiography results at entry (p = 0.005), peripheral
      vascular disease (p = 0.019), claudication (p = 0.044), diabetes (p = 0.008), and
      history of hypertension (p = 0.044). The increase in risk indicated by the odds
      ratios (OR) were moderate (OR < 2.00) for each of the clinical risk factors
      except for CHF. Sixteen of 27 patients (59%) with a history of CHF at entry to
      the study died during follow-up (OR = 2.67). Arteriographic predictors of
      increased mortality rates included bilateral carotid artery stenosis and
      intracranial vascular disease (ICVD). With bilateral stenosis, 42% (80 of 190
      patients) died compared with 33% (83 of 252 patients) with unilateral stenosis (p
      = 0.062). With ICVD, 43% (56 of 130 patients) died compared with 34% (107 of 314
      patients) of those without ICVD (p = 0.073). Multivariate analysis demonstrated
      that three risk factors were significantly associated with an increased risk of
      death: diabetes, abnormal electrocardiography results, and claudication. Patients
      with two or three of these risk factors demonstrated annual mortality rates of
      11.3% and 13%, respectively. This was significantly higher than patients with
      none of these risks (OR = 2.95 and OR = 4.06, respectively). CONCLUSION: Adult
      male patients with high-grade asymptomatic carotid artery stenosis demonstrate a
      mortality rate of 37% at a mean follow-up of 4 years. Although age was not a risk
      for increased mortality rates in this population, diabetes, abnormal
      electrocardiography results, and claudication were significant. Patients with two
      or three of these risk factors were at high risk of death and may require
      aggressive treatment of their concurrent medical diseases.

PMID- 8264029
TI  - Unilateral renal artery revascularization can salvage renal function and
      terminate dialysis in selected patients with uremia.
AB  - Revascularization of renal arteries to salvage glomerular function in patients
      with chronic renal failure is performed infrequently. However, during the past 12
      months we have encountered three patients over 60 years of age known to have
      chronic renal failure who were on dialysis for 2 weeks, 3 weeks, and 2 months,
      respectively. All three patients were hypertensive, requiring between four and
      five antihypertensive medications. One patient was ventilator dependent in
      intractable cardiac failure with pulmonary artery systolic pressures ranging from
      60 to 70 mm Hg. Standard biplanar arteriography revealed occlusion of the left
      renal artery with distal reconstitution in two patients and a 99% stenosis of the
      right renal artery in the remaining patient. The contralateral renal artery was
      totally occluded in two patients and diffusely stenotic in one. The recipient
      kidneys measured 8, 10, and 11 cm in length. Kidney function was assessed by
      renal scintigraphy and creatinine clearance. Two splenorenal bypasses and one
      hepatorenal bypass with 6 mm polytetrafluoroethylene graft were performed
      successfully. After surgery, renal function improved in all patients with two of
      three patients resuming normal function as evidenced by reduction of serum
      creatinine levels to 0.9 and 1.3 mg/dl. The third patient recovered to have a
      creatinine level of 3.2 mg/dl. All patients were discharged home within 1 month
      with a daily urine output greater than 1500 ml. At discharge, each patient
      required only two antihypertensive medications to control blood pressure. Duplex
      scanning 3, 6, and 12 months after surgery confirmed patency of all
      reconstructions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264030
TI  - Long-term results of tissue development and cell differentiation on Dacron
      prostheses seeded with microvascular cells in dogs.
AB  - PURPOSE: The purpose of this study was to investigate in vivo the long-term
      development, differentiation, and proliferation of the subendothelial tissue on
      Dacron prostheses seeded with microvascular cells (MVC). METHODS: Autologous MVC
      from omental adipose tissue were seeded on 4 mm Dacron prostheses and the
      prostheses interposed in the carotid arteries of mongrel dogs for 5, 13, and 26
      weeks. RESULTS: Light and electron microscopic evaluation of patent seeded
      prostheses demonstrated an almost complete monolayer of endothelial cells and
      well-organized subendothelial tissue, whereas patent control prostheses were
      mainly covered by red and white thrombi, which were partially replaced by
      organized tissue with increased implantation time. The measurements of the
      thickness of the luminal cell layer in seeded and control grafts showed no
      statistically significant increase between 5 and 26 weeks of implantation. The
      subendothelial tissue of seeded prostheses demonstrated a time-dependent
      maturation of highly synthesizing myofibroblasts embedded in a collagen matrix to
      cells with features of smooth muscle cells located in a collagen-elastin matrix.
      In control grafts examined after 26 weeks the spontaneous endothelialization was
      accompanied by a delayed or incomplete maturation of subendothelial tissue.
      CONCLUSIONS: Our study indicates that MVC seeded onto Dacron prostheses are able
      to generate a vascular wall that does not continue to proliferate after prolonged
      implantation and that increasingly resembles the wall of a normal artery in cell
      differentiation and intercellular matrix.

PMID- 8264031
TI  - Functional foot salvage after extensive plantar excision and amputations proximal
      to the standard transmetatarsal level.
AB  - PURPOSE: It is generally accepted that when necrosis extends proximal to the
      transmetatarsal level a viable and functional foot can no longer be preserved and
      a major (above- or below-knee) amputation must be performed. However, with
      continuing advances in operations for limb salvage we felt the need to reexamine
      this concept. METHODS: In 1983 we initiated a prospective study to evaluate the
      role of extended foot amputations. All ambulatory patients with necrosis
      extending proximal to the transmetatarsal level (but not involving the whole
      foot) were included in the study. Among the 21 patients studied amputations
      ranged from open guillotine transmetatarsal amputation to removal of the medial
      or lateral three fifths of the foot. Five of these patients had adequate pedal
      circulation by clinical and laboratory criteria. The remaining 16 required
      vascular reconstruction to improve pedal flow. RESULTS: Eighteen (86%) of 21
      patients had complete healing of the foot amputations and were ambulatory at the
      time of discharge from the hospital. Two patients required early above- or below
      knee amputations. Three additional patients sustained limb loss in the follow-up
      period. The cumulative graft patency rate was 94% at 12 months. The cumulative
      limb salvage rate at 24 months was 84%. The operative mortality rate was 1 (5%)
      of 21. CONCLUSION: Our experience in a small number of patients suggests that
      functional foot salvage is possible even when necrosis or gangrene extends
      proximal to the transmetatarsal level.

PMID- 8264032
TI  - The incidence of deep venous thrombosis in patients undergoing abdominal aortic
      aneurysm resection.
AB  - PURPOSE: Fifty consecutive patients undergoing abdominal aortic aneurysm
      resection were studied prospectively for the presence of deep venous thrombosis
      (DVT) after surgery. METHODS: Bilateral venography was performed 5 days after
      surgery in all patients. There were 42 men and 8 women, with a mean age of 70
      years (range 60 to 83 years). No patients received DVT prophylaxis before
      surgery. RESULTS: Nine (18%) of 50 patients had a venogram positive for acute
      DVT. Nine (21%) of 42 men and none of eight women had DVT. Six patients had DVT
      in the left leg and three patients in the right leg. No patients had symptoms to
      suggest DVT. Seven (78%) of the nine patients with DVT had thrombi in the calf
      veins and two patients (22%) had thrombi in the more proximal venous segments,
      representing 14% and 4% of the entire series, respectively. No clinically evident
      pulmonary emboli were observed. CONCLUSIONS: Eighteen percent of 50 consecutive
      patients undergoing abdominal aortic aneurysm resection had DVT. Because of this
      high incidence, a study should be undertaken to determine whether DVT prophylaxis
      can lower the incidence of DVT after abdominal aortic aneurysm resection.

PMID- 8264033
TI  - The use of endovascular techniques for the treatment of complications of aortic
      dissection.
AB  - Intravascular ultrasonography, balloon angioplasty, stent placement, and
      endovascular septal fenestration have been used in the evaluation and treatment
      of vascular complications of acute and chronic aortic dissection in five
      patients. There were three men and two women with an average age of 52 years
      (range 39 to 64 years). There were three chronic type A dissections, one acute
      type B, and one subacute type B dissection. Intravascular ultrasonography was
      used in all five cases. The three patients with chronic type A dissections
      underwent unilateral renal artery angioplasty (RA PTA) and stent placement; one
      patient with an acute type B dissection and associated fibromuscular dysplasia
      underwent bilateral RA PTA without stent placement. These procedures were
      performed to ameliorate severe hypertension. The final patient, with a subacute
      type B dissection, underwent iliac artery stenting to correct severe lower
      extremity ischemia. During a second intervention, this patient, who also had
      bowel ischemia and nonresolving acute renal failure, underwent balloon dilatation
      of a preexisting septal fenestration to augment visceral blood supply and
      bilateral RA PTA and stent placement in an effort to improve renal function. This
      patient eventually died of gut ischemia. After RA PTA and stent placement, one
      patient had a major intrarenal hemorrhage that required coil embolization and
      transfusion. In the four survivors, RA PTA and stent placement resulted in
      immediate improvement in blood pressure control. This response has been sustained
      during follow-up intervals ranging from 8 to 18 months (average 10 months).
      Intravascular ultrasonography can clearly demonstrate the pathologic anatomy
      associated with aortic dissection (even when angiography is ambiguous) and is
      essential for guiding therapeutic endovascular interventions. Further exploration
      of the efficacy of these endovascular techniques is warranted in this high-risk
      group of patients with aortic dissection who have appropriate clinical
      indications.

PMID- 8264034
TI  - A case of cystic adventitial disease of the popliteal artery demonstrated by
      magnetic resonance imaging.
AB  - In a 45-year-old man, who was free of symptoms after a 3 1/2-month period of calf
      claudication, a diagnosis of cystic adventitial disease was confirmed by magnetic
      resonance imaging. At operation a 12 cm long intramural cyst of the popliteal
      artery, continuous with a cyst around a genicular arterial branch, was found.
      Total resection of the cyst and its branch was performed. We recommend computed
      tomography or magnetic resonance imaging as the diagnostic tools of first choice
      in young patients who are free of arteriosclerosis and who have episodes of
      intermittent claudication of the calf.

PMID- 8264035
TI  - Transluminal placement of a prosthetic graft-stent device for treatment of
      subclavian artery aneurysm.
AB  - A 78-year-old man was seen with an expanding 5 cm false aneurysm of the right
      subclavian artery. This was treated by an intraluminal graft-stent device
      introduced through the brachial artery via a 16 F sheath. The graft was
      constructed from two polytetrafluoroethylene patches of 0.4 mm thickness and
      anchored in the subclavian artery by an 8 mm stainless steel stent. The procedure
      was monitored by an image intensifier. Completion arteriography and postoperative
      duplex scanning confirmed normal flow through the subclavian artery with no
      communication between the lumen and the aneurysmal sac. The patient recovered
      without complication.

PMID- 8264036
TI  - Penetrating thermal vascular injury in a child: a case report.
AB  - Penetrating vascular trauma in children is most commonly seen in wartime settings
      or more recently as a result of attempts at invasive imaging. Treatment of these
      patients can be more complicated than treatment of trauma in adults and must
      include maintenance of symmetric limb growth, compensatory growth of the vascular
      graft and its anastomoses, and the need for very long-term graft patency. This
      report describes the care of a 5-year-old child who was impaled by a hot metal
      pipe and sustained a penetrating thermal injury to the distal external iliac
      artery and vein. Issues such as conduit choice, extraanatomic reconstruction,
      anastomotic suture technique, and soft tissue coverage are reviewed in the
      report.

PMID- 8264037
TI  - Iliac vein compression syndrome: an unusual cause of varicocele.
AB  - Iliac vein compression syndrome is the phenomenon of nonthrombotic iliac vein
      obstruction caused by compression of left iliac vein between the right iliac
      artery and fifth lumbar vertebra. Affected patients usually present with
      unilateral leg edema. The condition is most often seen in women, in whom it may
      also be a cause of vulvar varicosities. Presented here is a case of idiopathic
      iliac vein obstruction associated with an ipsilateral varicocele in a young man.
      This varicocele was caused by multiple collateral venous channels and was
      resistant to surgical high ligation. This case illustrates an unusual cause of
      varicocele formation and an anatomic reason for failure of standard surgical
      therapy.

PMID- 8264038
TI  - Carotid artery stenosis: what's in the measurement?

PMID- 8264039
TI  - Thrombolysis for occluded vein bypass grafts through surgical access.
AB  - PURPOSE: This report describes surgical access to occluded vein grafts for
      thrombolysis by direct cutdown where indirect angiographic techniques have
      failed. METHOD: A sheath is introduced directly into the proximal vein graft.
      Distal thrombus is lysed following standard protocol. The residual thrombus at
      the origin of the graft is removed surgically, and the area is closed with a
      patch angioplasty. RESULTS: Distal thrombus was completely lysed in two vein
      grafts without bleeding complications. CONCLUSION: The thrombus "cork" that forms
      at the upper end of an occluded vein graft may deflect the angiographer's guide
      wire, but the distal thrombus usually remains soft and amenable to lysis.
      Angiographic access should not be a limiting factor in thrombolysis of an
      occluded vein graft.

PMID- 8264040
TI  - Regarding "Endovascular surgery credentialing and training for vascular surgery".

PMID- 8264041
TI  - Regarding "Endovascular surgery credentialing and training for vascular surgery".

PMID- 8264042
TI  - In situ replacement of infected vascular prostheses with rifampin-soaked vascular
      grafts.

PMID- 8264043
TI  - Regarding "Use of antibiotic-bonded graft for in situ reconstruction after
      prosthetic graft infections".

PMID- 8264044
TI  - Regarding: "Complications of missed arterial injuries".

PMID- 8264045
TI  - Malpractice and the vascular surgeon.

PMID- 8264046
TI  - Dobutamine stress echocardiography for cardiac risk assessment before aortic
      surgery.
AB  - PURPOSE: This study evaluates dobutamine stress echocardiography (DSE) for
      perioperative cardiac risk assessment with elective aortic surgery. METHODS:
      Dobutamine stress echocardiography was used to evaluate 81 patients before
      infrarenal aortic surgery. Patients were placed into three groups. Group I (n =
      31) had normal DSEs. Group II (n = 25) had resting wall motion abnormalities
      without dobutamine-induced changes of ischemia. Group III (n = 25) had evidence
      of dobutamine-induced ischemia. Patient analysis revealed that of 46 patients
      with clinical indicators of coronary artery disease (CAD), only 23 had DSEs with
      inducible ischemia. Two of 35 patients without clinical indicators of CAD had
      DSEs with inducible ischemia. RESULTS: The 56 patients in group I and II
      underwent aortic reconstruction without cardiac complications or death. Of the 25
      patients in group III, surgery was deferred in five (two patients with
      claudication and three with aneurysms < or = 5 cm), and four underwent coronary
      artery bypass grafting. Outcome after coronary artery bypass grafting included
      one death from stroke, one aneurysm rupture, and two uncomplicated aortic
      reconstructions. The remaining 16 patients in group III underwent aortic surgery,
      with three postoperative myocardial infarctions (MI) and no deaths. CONCLUSIONS:
      Using DSE for preoperative assessment of cardiac risk allowed us to operate on 74
      of 81 patients being considered for elective aortic reconstruction, with no
      operative deaths and a 4.1% rate of perioperative MI. Dobutamine stress
      echocardiography has the ability to identify patients with asymptomatic stress
      induced ischemic myocardium and its increased risk for perioperative MI (p <
      0.001). Equally important, for patients with clinical indicators of CAD but
      without DSE-inducible ischemia, no further cardiac evaluation is necessary.

PMID- 8264047
TI  - Pulmonary risk factors of elective abdominal aortic surgery.
AB  - PURPOSE: The purpose of this study was to retrospectively identify risk factors
      for postoperative pulmonary complications in patients undergoing elective
      abdominal aortic surgery via a midline incision. METHODS: We reviewed 181
      consecutive patients who underwent operation between July 1986 to December 1992.
      Preoperative factors analyzed included age, sex, diabetes mellitus, history of
      smoking, chronic obstructive pulmonary disease, obesity, indication for surgery
      (aneurysm [126] or aortoiliac occlusive disease [AIOD] [55]), history of coronary
      artery disease, length of preoperative hospital stay, American Society of
      Anaesthesiologists class, and pulmonary function tests. Intraoperative factors
      analyzed included endotracheal tube diameter, percent of inspired oxygen, blood
      loss, blood and crystalloid replacement, total operative time, epidural
      analgesia, and stress ulcer prophylaxis. RESULTS: Although the operative
      mortality rate was only 1.7% (3 of 181), major pulmonary complications occurred
      in 29 (16%) patients, including two lung-related deaths. Pneumonia occurred in 17
      (9%) patients, prolonged intubation greater than 24 hours occurred in nine (5%),
      and reintubation caused by pulmonary insufficiency occurred in three (2%). On
      univariate analysis, the following were associated with major pulmonary
      complications (p < 00.05): American Society of Anaesthesiologists class IV, age
      greater than 70 years, ideal body weight greater than 150%, forced vital capacity
      of 80% or less predicted, forced expiratory flow rate (25 to 75) of 60% or less
      predicted, crystalloid replacement greater than 6 L, and total operative time
      greater than 5 hours. CONCLUSIONS: The presence of these pulmonary risk factors,
      notably increased age and weight, decreased forced vital capacity and forced
      expiratory flow rate (25 to 75), and expected prolonged operative time,
      influences our decision not to proceed with surgery for small aortic aneurysms or
      for AIOD causing claudication. Patients at high pulmonary risk with AIOD who
      require revascularization for limb salvage would be more likely to undergo
      extraanatomic bypass. Pulmonary risk factors may play as important a role as
      cardiac factors in elective aortic surgery.

PMID- 8264048
TI  - An alternative method of salvaging occluded suprainguinal bypass grafts with
      operative angioscopy and endovascular intervention.
AB  - PURPOSE: A study of technical feasibility was undertaken to determine whether
      angioscopy and parallel endovascular instrumentation could effectively evaluate
      and restore inflow into occluded suprainguinal grafts. METHODS: Several
      endobronchial instruments were selected for adaptation for use in clearing
      occluded grafts under angioscopic guidance. These instruments were used in the
      treatment of 12 thrombosed grafts limbs in 10 patients who were admitted 1 to 40
      days after occlusion. The occluded suprainguinal graft limbs were exposed just
      proximal to the femoral anastomosis. Blind retrograde balloon thrombectomy and
      clot extraction were performed. Graft limbs underwent angioscopy, and the
      presence of luminal defects were recorded. Endoluminal instruments were then
      inserted parallel to the angioscope, and luminal defects were corrected. After
      inflow was reestablished, the distal portion of the graft was thrombectomized,
      and any necessary distal revisions were performed. RESULTS: Blind retrograde
      thrombectomy was successful in restoring inflow deemed normal in (67%) eight of
      12 graft limbs and present but diminished in two (17%) graft limbs. Balloon
      thrombectomy was ineffective in restoring graft flow in two (17%) graft limbs.
      Angioscopy revealed luminal defects in 10 (83%) graft limbs after blind
      retrograde thrombectomy. Only 2 (17%) graft limbs had no luminal defects after
      thrombectomy. Findings included pseudointimal flap in eight of 12 (67%), adherent
      residual thrombus in 4 (33%), and kinked graft limbs in 2 (17%) graft limbs.
      Endovascular instrumentation was successful in resecting all luminal disease
      under angioscopic guidance. There were no deaths, no episodes of graft injury or
      distal embolization, and only one groin hematoma. During a mean follow-up period
      of 6 months (2 to 13 months), there was one late reocclusion at 7 months.
      CONCLUSION: We conclude that angioscopically guided thrombectomy and endovascular
      graft revision is a useful approach to the treatment of the occluded
      suprainguinal graft. Enhanced luminal visualization permits refined diagnostic
      assessment and definitive therapy. This may prolong the benefit of suprainguinal
      reconstructions.

PMID- 8264049
TI  - Hereditary protein S deficiency in a large New Jersey kindred.
AB  - PURPOSE: Protein S is a vitamin K-dependent anticoagulant protein that serves as
      a cofactor for activated protein C. Deficiency of protein S has been associated
      with recurrent thrombotic events. To characterize better the risks of thrombosis
      in protein S deficiency, we studied 62 members in a large kindred. METHOD: All
      members were evaluated by a thorough clinical history. Plasma samples were
      assayed for total protein S antigen and protein S activity. Upper and lower
      extremity venous duplex examinations were performed in the majority of adult
      members. RESULT: Twenty-six (40%) of the 62 family members were classified as
      deficient on the basis of either low total protein S antigen levels or low
      protein S functional activity. Five members deficient in protein S had 16 venous
      thrombotic events. In all members the onset of thrombotic events occurred after
      19 years of age, with a tendency for recurrence. Three lower extremity deep
      venous thromboses that had been occult previously were first diagnosed on
      surveillance duplex scanning. Only one member whose protein S level was not
      deficient had a single episode of superficial thrombophlebitis. CONCLUSION: Our
      findings in this large kindred confirm an autosomal-dominant inheritance pattern.
      Thrombotic events occurred after the age of 19 years in affected individuals and
      tended to be recurrent. The diagnosis of protein S deficiency is based on
      functional and immunologic plasma assays. In this study venous duplex scanning
      proved to be a useful diagnostic adjuvant.

PMID- 8264050
TI  - Ambient oxygen tension modulates endothelial fibrinolysis.
AB  - PURPOSE: Vascular procedures reoxygenate ischemic endothelial cells (EC) and
      arterialize saphenous vein (HSV) EC. The balance between the EC-derived
      fibrinolytic components, plasminogen activator (tPA), and plasminogen inhibitor
      (PAI-1) contributes to maintaining thromboresistance. This balance also affects
      proteolysis through plasmin generation, mediating matrix metabolism endothelial
      migration, angiogenesis, and theoretically affecting the development of intimal
      hyperplasia. METHODS: To explore the impact of varying oxygen tensions on EC
      fibrinolysis, HSV and human umbilical vein (HUV) were subjected to Po2 of 40 mm
      Hg for 24 hours with restoration of Po2 to 150 mm Hg for 24 hours. The tPA and
      PAI-1 antigen and tPA/PAI-1 antigen ratio in conditioned media (CM), expressed as
      increases or decreases % change, normalized for cell count, versus controls, were
      analyzed by enzyme-linked immunosorbent assay. Cellular tPA and PAI-1 mRNAs were
      assessed by Northern analysis. RESULTS: The tPA but not PAI-1 was significantly
      decreased after the first 24 hours in HSVEC and significantly decreased after 48
      hours in both HUVEC and HSVEC when compared with controls. Messenger RNA for tPA
      was unchanged but PAI-1 mRNA increased significantly for HSVEC and HUVEC after 24
      hours of Po2 of 40 mm Hg, returning to baseline within 24 hours of Po2 to 150 mm
      Hg restoration. CONCLUSIONS: These data support the hypothesis of a fibrinolytic
      shift after altered ambient O2 tensions exposure in endothelium and demonstrate
      that HSVEC are more sensitive to altered O2 tension than HUVEC. Altered O2
      tensions depress EC fibrinolysis in this model.

PMID- 8264051
TI  - Autoradiographic mapping and characterization of insulin-like growth factor-I
      receptor binding in human greater saphenous vein.
AB  - PURPOSE: The proliferation of vascular smooth muscle cells is an important step
      in the process of intimal hyperplasia. Veins exposed to arterial pressure develop
      intimal hyperplastic lesions that lead to failure of vein bypasses. Insulin-like
      growth factor-I is a polypeptide hormone structurally related to insulin with
      insulin-like metabolic effects. Insulin-like growth factor-I has been found to
      work in concert with other growth factors, including platelet-derived growth
      factor, to promote the growth of vascular smooth muscle cells in culture. Insulin
      like growth factor-I exerts its effects via specific receptors located on the
      cell surface. We studied the in situ distribution of insulin-like growth factor-I
      receptor binding using autoradiography and examined insulin-like growth factor-I
      binding characteristics in normal human greater saphenous vein. METHODS: Frozen
      sections 20 microns thick were prepared from the greater saphenous vein
      specimens. The sections were incubated in a buffer containing 125I-insulin-like
      growth factor-I in the presence of increasing concentrations of the unlabeled
      peptide. Autoradiograms were obtained by apposing the treated sections to
      autoradiography film. RESULTS: Analysis of the autoradiographs showed that
      insulin-like growth factor-I binding was consistently present in the wall of
      human greater saphenous vein. To characterize these binding sites binding
      inhibition studies were performed. High-affinity insulin-like growth factor-I
      receptor binding was found with dissociation constant of 1.0 +/- 0.32 nmol/L and
      maximum binding capacity of 0.46 +/- 0.23 pmol/mg protein. These values are
      consistent with a physiologic role for insulin-like growth factor-I in the tissue
      examined. CONCLUSIONS: The presence of high-affinity (dissociation constant = 1.0
      +/- 0.32) insulin-like growth factor-I binding sites in the wall of saphenous
      vein suggests that insulin-like growth factor-I plays an important role in
      regulating the proliferation of venous wall cellular components, an essential
      step in the process of venous intimal hyperplasia.

PMID- 8264052
TI  - Hemodynamics and aneurysm development in vascular allografts.
AB  - PURPOSE: Mechanical and immunologic factors may play a role in the development of
      native arterial and biologic graft aneurysms. We developed an experimental rat
      aortic allograft aneurysm model in which segments of infrarenal aorta were
      transplanted between hypertensive and normotensive rats to study these factors in
      this model. METHODS: Aortic allografts and autografts were inserted into
      spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats.
      Effects of immunologic and antihypertensive therapy were evaluated. Graft
      diameters were followed up with magnetic resonance imaging and at harvest. Direct
      pressure measurements were taken and dp/dtmax (force of ventricular contractions)
      was calculated before harvest. RESULTS: Autografts remained isodiametric and
      maintained their histologic architecture. Aneurysmal dilation of transplanted
      segments occurred in SHR host allografts but not in WKY host allografts.
      Histologic examination of all allograft specimens noted a rejection reaction
      characterized by inflammatory cell infiltration and medial smooth muscle cell
      loss. Antigenic enhancement accelerated aneurysm development in SHR hosts but had
      no significant effect on WKY hosts. Rates of allograft enlargement and final
      allograft diameters were similar in antihypertensive treated and untreated SHR
      hosts. The dp/dtmax in untreated SHR hosts was greatest and differed
      significantly from that in the WKY rats but only marginally from that in treated
      SHR hosts. CONCLUSIONS: Immunologic rejection but not abnormal hemodynamics is
      necessary for development of allograft aneurysm in this model.

PMID- 8264053
TI  - Early results with cryopreserved saphenous vein allografts for infrainguinal
      bypass.
AB  - PURPOSE: Cryopreserved saphenous vein allografts (CSVA) are available for use in
      arterial reconstructions; however, patency rates in the infrainguinal position
      are not well described. METHODS: We reviewed our experience with 38 patients who
      underwent 43 infrainguinal bypasses with CSVA as the conduit. The group includes
      21 women and 17 men with a mean age of 69 +/- 11 years. Mean follow-up is 8.2 +/-
      5.5 months. Logistic regression was used to analyze five variables in an attempt
      to identify predictors of success or failure: distal anastomosis to the popliteal
      artery versus a crural artery, one-vessel versus two- or three-vessel runoff,
      postoperative anticoagulation versus none, primary reconstructions versus
      reoperations, and one segment versus two segments of CSVA required. RESULTS: The
      cumulative patency rate at 12 months by life-table analysis is 66%. Logistic
      regression revealed that primary reconstructions were more likely to succeed than
      reoperations (p = 0.03) and operations completed with one segment of CSVA were
      more likely to succeed than those requiring more than one segment of vein (p =
      0.03). CONCLUSIONS: We conclude that (1) the short-term patency of infrainguinal
      bypasses with CSVA suggests that they may be acceptable alternatives to
      prosthetic grafts in the below-knee position, and (2) primary reconstructions
      performed with one segment of CSVA are more likely to succeed.

PMID- 8264054
TI  - Extension of limb salvage by combined vascular reconstruction and adjunctive free
      tissue transfer.
AB  - PURPOSE: Vascular reconstruction alone can be insufficient for extremity salvage
      in some patients with severe soft-tissue wounds. We present our experience in 20
      patients with vascular reconstruction for ischemic disease and free-tissue
      transfer for limb-threatening soft-tissue wounds. METHODS: Nineteen patients
      underwent autogenous venous bypasses and one patient underwent an aortobifemoral
      bypass. Ten soft-tissue reconstruction were performed at the time of the vascular
      reconstruction and 10 were delayed. Free-tissue transferred included muscle,
      fasciocutaneous flaps, and omentum. Inflow to the flap was from the bypass graft
      (n = 12) or the distal tibial artery. RESULTS: One free flap and graft failed
      immediately in the same patient. One successful flap and graft required a below
      knee amputation for ongoing infection in the surrounding soft tissues. Eighteen
      of 20 patients have had free-flap and graft patency during the mean follow-up
      period of 17 months (range 6 to 33 months). These 18 patients ambulate
      independently. CONCLUSIONS: In patients with arterial insufficiency and severe
      soft-tissue wounds, combined vascular reconstruction and free-tissue transfer
      permits extended limb salvage with excellent functional results.

PMID- 8264055
TI  - Is surveillance to detect failing polytetrafluoroethylene bypasses worthwhile?:
      Twelve-year experience with ninety-one grafts.
AB  - PURPOSE: The purpose of this study was to review the 91 failing
      polytetrafluoroethylene (PTFE) grafts that were treated at our institution over
      the past 12 years to better understand their cause and improve the diagnosis and
      treatment of these grafts. METHODS: Eighty-five patients with 91 failing grafts
      were retrospectively reviewed. The 144 graft-threatening lesions associated with
      these grafts were characterized by location (inflow artery, outflow artery,
      anastomosis, or graft body) and treatment method used (surgery, balloon
      angioplasty, or thrombolysis). RESULTS: Progression of atherosclerotic disease
      was the predominant cause of failing PTFE grafts with 43 inflow lesions and 83
      outflow lesions, accounting for 87% of all lesions identified. Ten lesions (7%)
      were noted within the prosthetic grafts, whereas only eight (6%) lesions were
      noted at the anastomoses. Forty stenotic lesions 2 cm in length or less were
      treated with percutaneous transluminal balloon angioplasty, whereas 100 lesions
      were treated by patch angioplasty or graft extensions. The remaining four
      lesions, present within the prosthetic grafts, were treated with thrombolytic
      therapy. The 5-year cumulative patency rate for all failing PTFE grafts was 71%,
      whereas that of failing femoropopliteal PTFE grafts was 64%. The 5-year limb
      salvage rate for all failing PTFE grafts was 73%. CONCLUSIONS: The progression of
      inflow and outflow disease is the predominant cause of failing PTFE grafts, which
      suggests that this process is a more important cause of PTFE graft thrombosis
      than is generally recognized. Frequent PTFE graft surveillance may permit
      detection of some threatening lesions before graft thrombosis occurs and may help
      maintain and prolong graft patency. The enhanced 5-year patency and limb salvage
      rates for treated failing PTFE grafts compared with the known poor outcome after
      reinterventions for PTFE graft failure support the conclusion that surveillance
      of PTFE grafts is worthwhile.

PMID- 8264057
TI  - From the Centers for Disease Control and Prevention. Reduction in alcohol-related
      traffic fatalities--United States, 1990-1992.

PMID- 8264056
TI  - Long-term follow-up of patients undergoing reoperation for recurrent carotid
      artery disease.
AB  - PURPOSE: We examined the perioperative course and long-term fate of individuals
      who required reoperation for recurrent carotid artery disease. METHODS: The
      records of 2289 patients undergoing 2961 consecutive operations during a 22-year
      period were reviewed. Forty-two patients (1.8%) who underwent reoperations were
      studied. Forty-seven redo carotid artery reconstructions were performed on these
      42 patients for neurologic symptoms or asymptomatic high-grade stenosis. Long
      term follow-up was obtained on 41 of 42 patients (mean 54 months; range 9 to 202
      months). RESULTS: The forty-seven reoperations consisted of endarterectomy with
      patch angioplasty (n = 36), saphenous vein or polytetrafluoroethylene
      interposition graft (n = 7), or simply vein or polytetrafluoroethylene patch
      angioplasty (n = 4). There were no perioperative strokes or deaths. Three
      patients had perioperative transient ischemic attacks and two had cranial nerve
      injuries. The incidence of late failure after secondary surgery was 19.5% (8/41
      patients). These failures consisted of one stroke, three transient ischemic
      attacks, and four asymptomatic occlusions. One tertiary carotid artery
      reconstruction was performed for a restenosis at the site of the secondary
      reconstruction. CONCLUSION: The factors responsible for the high incidence of
      late failures after secondary carotid artery reconstruction are unclear.
      Reoperation for recurrent carotid artery disease appears less durable than
      primary carotid endarterectomy. Close postoperative surveillance is recommended
      after carotid artery reoperation.

PMID- 8264058
TI  - Pneumocystis carinii pneumonia in children with perinatally acquired HIV
      infection.

PMID- 8264059
TI  - Pneumocystis carinii pneumonia in children with perinatally acquired HIV
      infection.

PMID- 8264060
TI  - Pneumocystis carinii pneumonia in children with perinatally acquired HIV
      infection.

PMID- 8264061
TI  - Treating multidrug-resistant tuberculosis: compliance and side effects.

PMID- 8264063
TI  - Contempo: instrumented spinal fusions.

PMID- 8264062
TI  - Treating multidrug-resistant tuberculosis: compliance and side effects.

PMID- 8264064
TI  - Contempo: pediatrics.

PMID- 8264065
TI  - Syringe and needle exchange as HIV/AIDS prevention for injection drug users.
AB  - OBJECTIVE: To evaluate an all-volunteer syringe exchange program in San
      Francisco, Calif. DATA SOURCES: Syringe exchange program records and 11
      semiannual surveys administered during a 5.5-year period, using standard
      questionnaires. Interviews (N = 5644) were conducted with injection drug users
      recruited in two 21-day drug detoxification clinics and three street settings.
      MAIN OUTCOME MEASURES: Use of the syringe exchange program and self-reported data
      regarding sources of syringes, frequency of injection, initiation into drug
      injection, and frequency of syringe sharing. RESULTS: In spring 1992, 45%
      reported "usually" obtaining injection equipment from the syringe exchange, and
      61% reported using the program within the past year. During the period from
      December 1986 through June 1992, the median reported frequency of injection
      declined from 1.9 injections per day to 0.7 injection per day, the mean age
      increased from 36 to 42 years, and the percentage of new initiates into injection
      drug use decreased from 3% to 1%. In logistic regression analysis (of fall 1991
      through spring 1992 interviews; n = 752), we found six independent factors
      associated with syringe sharing. Protective from syringe sharing were use of the
      syringe exchange program, having received human immunodeficiency virus (HIV)
      testing and counseling, condom use, older age, and African-American race.
      Injection of cocaine was a predictor for syringe sharing. The strength of
      association between use of the syringe exchange program and not sharing syringes
      was greatest in injection drug users younger than the median age of 40 years.
      CONCLUSIONS: The syringe exchange program was rapidly adopted by injection drug
      users. Health interventions associated with not sharing needles included use of
      the syringe exchange program and voluntary, confidential HIV testing and
      counseling. Our data did not support the hypothesis that a syringe exchange
      program would stimulate increased drug abuse in terms of frequency of injection
      or recruitment of new and/or younger users.

PMID- 8264066
TI  - Continuity and change within an HIV epidemic. Injecting drug users in New York
      City, 1984 through 1992.
AB  - OBJECTIVES: To examine trends in acquired immunodeficiency syndrome (AIDS) risk
      behavior and human immunodeficiency virus (HIV) seroprevalence among injecting
      drug users (IDUs) in New York City from 1984 through 1992. DESIGN AND SETTING:
      Comparisons were made between two surveys of IDUs at the same hospital-based New
      York City drug abuse detoxification program: 141 IDUs in 1984 and 974 IDUs in
      1990 through 1992. National Death Registry, New York City Health Department, and
      drug treatment program records were also used. PARTICIPANTS: Persons attending
      detoxification program randomly selected for participation. Eligibility was based
      on injection within previous 2 months; 99% acceptance rates were obtained.
      Participants in the 1984 and 1990 through 1992 surveys were 66% and 79% men, 21%
      and 19% white, 33% and 34% African American, and 45% and 46% Latin American,
      respectively. INTERVENTIONS: Community-based AIDS prevention programs, including
      underground syringe exchanges. MAIN OUTCOME MEASURES: Acquired immunodeficiency
      syndrome risk behaviors; HIV serostatus; CD4+ cell counts; death rates among 1984
      subjects; and injection and intranasal routes of drug administration. RESULTS:
      The HIV seroprevalence remained stable at slightly more than 50%. Mean CD4+ cell
      counts declined from 0.716 x 10(9)/L (716/microL) to 0.575 x 10(9)/L (P < .009).
      Annual death rate among 1984 subjects was 3%, with a significantly higher rate
      among HIV-seropositive subjects (relative risk, 2.57; 95% exact binomial
      confidence interval, 1.12 to 6.61). Large-scale declines were observed in AIDS
      risk behaviors, eg, use of potentially contaminated syringes declined from 51% to
      7% of injections (P < .001). Recent additional risk reduction was associated with
      use of the underground syringe exchanges. Intranasal heroin use was the primary
      route of drug administration for 46% of heroin admissions to New York City drug
      treatment programs. CONCLUSIONS: The HIV seroprevalence has remained stable among
      this population of New York City IDUs for almost a decade. Continuation of
      current trends should lead to further reduction in HIV transmission, although
      reversal of the trend to intranasal use could lead to substantially increased
      transmission.

PMID- 8264067
TI  - Fall severity and bone mineral density as risk factors for hip fracture in
      ambulatory elderly.
AB  - OBJECTIVE: To determine the relative importance of fall characteristics, body
      habitus, and femoral bone mineral density (BMD) in predicting hip fracture in
      community-dwelling elderly. DESIGN: Prospective case-control study. SETTING:
      Community-based academic hospital. PARTICIPANTS: A total of 149 ambulatory,
      community-dwelling fallers (126 women, 23 men) aged 65 years and older, including
      72 case patients (fallers with hip fracture) and 77 control fallers (fallers with
      no hip fracture). MAIN OUTCOME MEASURES: Fall characteristics, body habitus,
      femoral BMD. RESULTS: Significant and independent risk factors for hip fracture
      in both sexes were direction of the fall (adjusted odds ratio [OR], 5.7; 95%
      confidence interval [CI], 2.3 to 14.0; P < .001); femoral neck BMD (a decrease of
      1 SD; adjusted OR, 2.7; 95% CI, 1.6 to 4.6; P < .001); potential energy of the
      fall (an increase of 1 SD; adjusted OR, 2.8; 95% CI, 1.5 to 5.2; P < .001); and
      body mass index (a decrease of 1 SD; adjusted OR, 2.2; 95% CI, 1.2 to 3.8; P <
      .01). Importantly, the OR for the fall direction was unaffected by the addition
      or removal of BMD from the model. CONCLUSIONS: We conclude that among elderly
      fallers--in most of whom hip BMD is already less than the fracture threshold-
      fall characteristics and body habitus are important risk factors for hip fracture
      and touch on a domain entirely missed by knowledge of BMD. These data suggest new
      targets for preventive therapy. In addition to the maintenance of bone density,
      reductions in fall severity (eg, by use of trochanteric padding or enhancement of
      muscle strength) may provide additional strategies for prevention of hip fracture
      in this age group.

PMID- 8264068
TI  - A clinical prediction rule for delirium after elective noncardiac surgery.
AB  - OBJECTIVE: To develop and validate a clinical prediction rule for postoperative
      delirium using data available to clinicians preoperatively. DESIGN: Prospective
      cohort study. SETTING: General surgery, orthopedic surgery, and gynecology
      services at Brigham and Women's Hospital, Boston, Mass. PATIENTS: Consenting
      patients older than 50 years admitted for major elective noncardiac surgery
      between November 1, 1990, and March 15, 1992 (N = 1341). MEASUREMENTS: All
      patients underwent preoperative evaluations, including a medical history,
      physical examination, laboratory tests, and assessments of physical and cognitive
      function using the Specific Activity Scale and the Telephone Interview for
      Cognitive Status. Postoperative delirium was diagnosed using the Confusion
      Assessment Method or using data from the medical record and the hospital's
      nursing intensity index. Patients were followed up for the duration of
      hospitalization to determine major complication rates, length of stay, and
      discharge disposition. RESULTS: Postoperative delirium occurred in 117 (9%) of
      the 1341 patients studied. Independent correlates included age 70 years or older;
      self-reported alcohol abuse; poor cognitive status; poor functional status;
      markedly abnormal preoperative serum sodium, potassium, or glucose level;
      noncardiac thoracic surgery; and aortic aneurysm surgery. Using these seven
      preoperative factors, a simple predictive rule was developed. In an independent
      population, the rule stratified patients into groups with low (2%), medium (8%,
      13%), and high (50%) rates of postoperative delirium. Patients who developed
      delirium had higher rates of major complications, longer lengths of stay, and
      higher rates of discharge to long-term care or rehabilitative facilities.
      CONCLUSIONS: Using data available preoperatively, clinicians can stratify
      patients into risk groups for the development of delirium. Since delirium is
      associated with a variety of adverse outcomes, patients with substantial risk for
      this complication could be candidates for interventions to reduce the incidence
      of postoperative delirium and potentially improve overall surgical outcomes.

PMID- 8264069
TI  - Prioritization and organ distribution for liver transplantation.

PMID- 8264070
TI  - Diarrhea associated with Cyanobacterialike bodies in an immunocompetent host. An
      unusual epidemiological source.
AB  - OBJECTIVE: To describe a patient who developed diarrhea secondary to
      Cyanobacterialike bodies (CLBs) after exposure to contaminated water in his home.
      DESIGN: Case report. SETTING: General community. PATIENT: Healthy, elderly man.
      INTERVENTION: None, self-limited illness. RESULTS: The patient's clinical course
      was consistent with illness caused by CLBs. Cyanobacterialike bodies were
      recovered from the patient's stool sample and the contaminated water to which he
      was exposed. CONCLUSION: Internists and laboratory technicians should be aware of
      CLBs as a cause of protracted diarrhea in the community.

PMID- 8264071
TI  - 'Into whatever houses I enter'. HIV and injecting drug use.

PMID- 8264072
TI  - Mammographic screening.

PMID- 8264073
TI  - Constellation of risks and processes seen in search for Alzheimer's clues.

PMID- 8264074
TI  - Could late spring bring an end to US military medicine's 'new world order' role
      in Somalia?

PMID- 8264075
TI  - NCI changes its stance on mammography.

PMID- 8264076
TI  - From the Institute of Medicine.

PMID- 8264077
TI  - Guidelines for the use of parenteral and enteral nutrition in adult and pediatric
      patients. American Society for Parenteral and Enteral Nutrition.

PMID- 8264078
TI  - Spontaneous sub-periosteal hematoma of the orbit: diagnosis on computed
      tomography.

PMID- 8264079
TI  - Family medicine: a brief review of its history and concepts and its relevance to
      Pakistan.

PMID- 8264080
TI  - Upper gastrointestinal bleeding in chronic renal failure.

PMID- 8264081
TI  - Role of colposcopy in the diagnosis and outpatient treatment of cervical
      intraepithelial neoplasia.
AB  - One hundred and seventy nine women with abnormal smears referred for colposcopy
      to the Samaritan Hospital were studied. After confirming CIN on repeat smear,
      colposcopy and histology, cone biopsy was carried out. One hundred and twenty one
      patients (68%) had treatment either with electrical loop diathermy under local
      anaesthesia (105 patients, 59%) or laser excision of transformation zone under
      general anaesthesia as a day case (16 patients, 9%). Cone biopsy was done in 121
      patients (32%). We conclude that colposcopy is a valuable tool in combination
      with cytology and histology for diagnosis and delineating the extent of CIN, thus
      avoiding unnecessary cone biopsies particularly in women of child bearing age.
      The majority of patients were treated by an outpatient procedure, which is easy
      to learn, safe, effective and inexpensive.

PMID- 8264082
TI  - Tamoxifen: an alternative approach in clomiphene resistant polycystic ovarian
      syndrome patients.
AB  - Twenty patients with ultrasound diagnosed polycystic ovaries and high luteinizing
      hormone levels who failed to respond to clomiphene citrate were given tamoxifen
      to induce ovulation. Tamoxifen 20 mg daily (group 1, n = 10) and 40 mg daily
      (group 2, n = 10) was given for 5 consecutive days from the third to seventh day
      of the cycle. Treatment was monitored by serial ultrasound scans and assessment
      of serum estradiol. Human chorionic gonadotrophin (hCG) was administered when at
      least one follicle was > 16mm and serum estradiol level was > 300 pg/ml per
      follicle. Ovulation was confirmed with detection of the follicular rupture
      ultrasonographically 2 days after hCG and midluteal progesterone levels. The
      ovulation rate achieved in group 2 patients was significantly higher (p = 0.01)
      than group 1. Three pregnancies were achieved in group 2 patients while there was
      no pregnancy in group 1. The only side effect was ovarian cyst formation in one
      patient in group 1. As a result, tamoxifen might be a good choice for clomiphene
      resistant patients prior to treatment with surgery or hMG.

PMID- 8264083
TI  - Retained stones in the common bile duct: results of management.
AB  - Seventeen patients underwent treatment for retained common bile duct stones. In 7
      patients the stones were removed via a T-tube tract using steerable catheters
      while 5 patients underwent ERCP and sphincterotomy and 5 underwent surgical re
      exploration. Considering morbidity, mortality, success rate and patients' stay in
      the hospital, non-operative modalities should be the treatment of choice for
      retained common bile duct stones.

PMID- 8264084
TI  - Mineral and parathyroid hormone inter-relationships in normal pregnancy and
      pregnancy-induced hypertension.
AB  - The serum of calcium, other involved minerals and parathyroid hormone (PTH) were
      studied in non-pregnant women, during pregnancy and in pregnancy-induced
      hypertension (PIH). In pregnant women, serum creatinine, total calcium, total
      protein, albumin, inorganic phosphorus and magnesium declined, while parathyroid
      hormone levels increased significantly when compared to non-pregnant women. In
      PIH cases, serum total proteins, albumin and inorganic phosphorus were further
      reduced, while PTH levels were further increased when compared to normal pregnant
      women. Serum ionised calcium and sodium levels were similar in all the three
      groups. No significant relationship between blood pressure, PTH and involved
      minerals was observed in this study.

PMID- 8264085
TI  - Endoscopic lesions in chronic renal failure.
AB  - To determine the frequency and type of upper gastrointestinal lesions in patients
      with chronic renal failure (CRF), upper G.I. endoscopy was done in 101 cases. Of
      the various mucosal lesions, inflammatory changes were seen maximally (40),
      followed by erosions (16) and ulcers (7). Other changes included atrophic gastro
      duodenal folds (17), pale mucosa (11) and moniliasis (6) which was only seen in
      patients with end stage CRF. Lesions were more frequent in those who were in
      advanced stage of CRF (81%) and those undergoing dialysis (79%), reflecting a
      positive correlation of upper G.I. lesions with the severity of CRF.

PMID- 8264086
TI  - Peptic ulcer in chronic renal failure.

PMID- 8264087
TI  - Prevalence of thalassemia minor trait in Pakistani population presented at Akuh
      for complete blood count estimation (CBC).

PMID- 8264088
TI  - Stage 1B carcinoma of cervix complicating pregnancy.

PMID- 8264089
TI  - Urologic J.J stents: uses and complications.

PMID- 8264090
TI  - Experience with indwelling "J.J" ureteral stents.
AB  - J.J stents provide free drainage from the kidney to the bladder, reduce or
      eliminate urine leakage and provide stenting of the ureter. They were used in a
      total of 200 cases. In 158 to prevent ureteric obstruction before extracorporeal
      shock wave lithotripsy (ESWL), in 25 to bypass obstruction and in 12 as an
      adjunct to complicated upper urinary tract surgery. Majority (97%) of the stents
      were placed endoscopically under local anaesthesia (71.5%). In all the cases
      stents were successful to provide free drainage. No mortality was attributable to
      the use of stents but certain complications were encountered. Encrustation of the
      stents occurred in 21 (10.5%) and migration in 11 (5.5%) cases. Stents were
      removed easily under local anaesthesia by cystoscope. "J" stents thus provide an
      effective means to reduce complications and enhance effectiveness specially of
      ESWL therapy.

PMID- 8264091
TI  - Does red blood cell distribution width (RDW) improve evaluation of microcytic
      anaemias?
AB  - The red cell distribution width (RDW) is an index of the variation in red cells
      size (anisocytosis). A study was conducted to examine the validity of using RDW
      in improving classification of microcytic anaemias. A total of 300 blood samples
      collected from a patient population aged 3 months to 55 years who were referred
      for haemoglobin electrophoresis were examined at the Aga Khan University Hospital
      (AKUH). On complete blood count, initially 200 patients (66.6%) were found to
      have hypochromic microcytic anaemia. Following haemoglobin electrophoresis 41%
      (82/200) patients were diagnosed to have thalassemia minor and 59% (118/200) had
      hypochromic microcytic anaemia with either a normal haemoglobin pattern or an
      abnormal haemoglobin. The mean (+/- SD) RDW estimated in 250 apparently healthy
      Pakistani population was 14 (+/- 1.5%). Elevated RDW of 23% was present in 94%
      (110/118) of the patients with hypochromic microcytic anaemia due to other
      causes, whereas 48% (39/82) of the patients with thalassemia minor had elevated
      RDW of 16%. Also, of the 82 thalassemia minor, 28 patients had normal haemoglobin
      level, of which 6 had elevated RDW and of the 54 with low haemoglobin level, 35
      had elevated RDW. RDW was normal in 41 patients with thalassemia minor trait. Our
      results suggest that RDW alone cannot be used as a reliable indicator to
      distinguish between thalassemia minor and other causes of microcytosis.

PMID- 8264092
TI  - Burkitt's lymphoma--a study of 50 consecutive cases.
AB  - A retrospective study of Burkitt's lymphoma done over a period of 7 years is
      presented. The relative frequency of Burkitt's lymphoma as compared to other non
      Hodgkin's lymphomas was 6.35%. Although Pakistan is non-endemic for Burkitt's
      lymphoma, but the frequency of the disease is higher than other non-endemic
      countries. There was male predominance (M:F 2.3:1). Majority of the cases were in
      pediatric age group and 12% were older than 35 years. The main clinical
      presentation was abdominal (42%), either in the intestinal tract (22%) or
      retroperitoneal (18%) region (American mode of presentation). Jaw tumour (4%)
      (African mode) was rare. Sporadic cases at almost all sites were also
      encountered. Burkitt's lymphoma presenting as primary nodal disease was seen in
      36% cases. Fifty-four percent showed bone marrow infiltration. The stage of the
      disease at diagnosis was advance in 54% cases. Follow-up of ten cases revealed
      poor survival inspite of treatment.

PMID- 8264093
TI  - Significance, isolation, identification and sensitivity of Branhaemella
      (moraxella) catarrhalis.
AB  - In a study lasting over two years the frequency and sensitivity of moraxella
      catarrhalis causing respiratory tract infections were studied. Sputum samples
      from patients with lower respiratory tract infections were screened for moraxella
      catarrhalis. The organisms isolated identified and their sensitivity determined
      by simple methods which are practicable. The study shows that 22.4% of the
      infections were due to moraxella catarrhalis and 98% of the isolates were
      sensitive to amoxicillin-culvanalic acid (augmentin). The paper signifies the
      importance of reporting moraxella catarrhalis and its treatment.

PMID- 8264094
TI  - Characteristics of depression in the elderly.

PMID- 8264095
TI  - Speculation and truth about the sequence of events in the pathogenesis of left
      heart failure.

PMID- 8264096
TI  - Disease pattern, health services utilization and cost of treatment in Pakistan.
AB  - Population based data on disease patterns, health services utilization and cost
      incurred on treatment in Pakistan were collected through a nation-wide sample
      survey in 1982-83. The survey for the first time revealed, the burden of disease
      on the society. The analysis done here suggest, that about one-sixth of the
      population suffered from an illness during the past one month period. As
      expected, illness was more prevalent among children, women in reproductive ages
      and the elderly. Over two-thirds of those who fell ill, suffered from malaria and
      fever and one-fifth from diarrhoea and dysenteries. There was heavy reliance on
      private physicians for treatment of those who fell, about two- thirds in the
      urban and one-third in the rural areas, consulted private physicians. On the
      other hand, in both the areas, less than one-sixth utilized the government health
      facilities. The cost of health care on an average, was 4% of the total income in
      the urban and 5% in the rural areas. In both the areas, this constituted over 7%
      of the monthly household income of the poorest. Suggestions are made to overcome
      the high cost of health care through broad based national health policy and
      implementation of primary health care programme.

PMID- 8264097
TI  - Roberts syndrome.

PMID- 8264098
TI  - Insertion of inferior vena caval filter and thromboembolic phenomenon.

PMID- 8264099
TI  - [Immunobiological effects of synthetic peptide segments of fimbrilin protein from
      Porphyromonas gingivalis].

PMID- 8264100
TI  - [Diphtheria toxin receptor].

PMID- 8264101
TI  - [The Regional Meeting of the Japanese Society of Gastroenterology. 1993.
      Abstracts].

PMID- 8264102
TI  - [Effect of high-dose thiazide treatment and low-K diet on citrate uptake by rat
      renal brush border membrane vesicles (BBMV)].
AB  - In order to study the effect of high-dose thiazide treatment and low-K diet on
      citrate uptake by rat renal brush border membrane, we measured citrate uptake by
      rat renal brush border membrane vesicles (BBMV) and analyzed the acid-base
      balance of non-treated rats, high-dose thiazide-treated rats and low-K diet rats.
      Seven-week male Wistar rats (Jcl) were housed in metabolic cages, given 10 mg/Kg
      BW/day hydrochlorothiazide (HCTZ) by a gastric tube once a day for 3 weeks (high
      dose thiazide treated rats) or a low-K diet for 3 weeks (low-K diet rats).
      Arterial blood was taken from the aorta and BBMV were prepared by the divalent
      cation precipitation method. Citrate uptake was measured by a Millipore rapid
      membrane filtration technique. High-dose thiazide treatment for 3 weeks showed a
      significant metabolic alkalosis and increase of urinary citrate excretion.
      However, it had no significant effect on citrate uptake by BBMV. On the other
      hand, low-K diet for 3 weeks showed significant hypokalemia, metabolic alkalosis
      and decrease in urinary citrate excretion. Moreover, it increased the maximal
      activity (Vmax) with no difference in citrate affinity (Km). These data suggested
      that urinary citrate excretion was more affected by the K depletion than by the
      acid-base balance.

PMID- 8264103
TI  - [Effects of nisoldipine in heminephrectomized spontaneously hypertensive rats-
      measurement of afferent and efferent arterioles by microvascular cast].
AB  - In this study, we measured cross sectional areas of glomerular arterioles and
      glomerular volume in heminephrectomized spontaneously hypertensive rats (SHR)
      treated with a calcium antagonist, nisoldipine (NSL). We also examined the
      relevance of these parameters to the progression of hypertensive renal injury.
      Male 6-week-old SHR (n = 14) were heminephrectomized and divided into 2 groups.
      They were fed regular chow (control, n = 7) or chow containing 0.1% NSL (n = 7).
      After 12 weeks, urinary protein excretion (UpV) and systolic blood pressure (SBP)
      were measured. The control rats developed marked hypertension reaching 228 +/- 2
      mmHg, and NSL lowered this by 27 mmHg (p < 0.001). NSL reduced UpV by 22% (p <
      0.05). Microvascular cast of the kidney was prepared, and the cross sectional
      areas of the afferent and efferent arterioles as well as glomerular volume were
      measured using scanning electron microscopy. In the juxtamedullary and
      subcapsular glomeruli with minor abnormalities, the afferent arteriole was
      narrower and the glomerular volume was smaller in the NSL-treated rats than in
      the control rats. These results suggest that the calcium antagonist, NSL, offers
      the advantage of protecting kidney from hypertensive injury by reducing afferent
      arteriolar diameter, glomerular hypertrophy and intraglomerular pressure in
      heminephrectomized SHR.

PMID- 8264104
TI  - [Effects of MRX-III on chronic renal failure in rats].
AB  - The effects of MRX-III, a new amino acid solution for renal failure, on survival,
      progression of renal insufficiency, metabolism of calcium and phosphorous, and
      nutritional status were studied in rats with chronic renal failure induced by 7/8
      renal ablation. These rats were injected intraperitoneally with MRX-III, an
      essential amino acid solution for renal failure (Amiyu; Sol. A) or a general
      amino acid solution (Moripron-F; Sol. M) for 12 weeks under the condition of a
      3.5% protein diet, and these effects were compared with those in control rats
      infused with Sol. M under a 22% protein diet.1) Infusion of MRX-III or the other
      solutions under a low protein diet prolonged survival time and improved the
      uremic status indicated by azotemia, polyuria, albuminuria, hypocalcemia and
      hypertension. 2) Increase in body weight and tissue weight of rats treated with
      MRX-III or Sol. A was better than those in rats treated with Sol. M. MRX-III as
      well as Sol. A showed a tendency to provide a better nutritional effect in
      comparison with Sol. M.

PMID- 8264105
TI  - [Shortening of life expectancy in patients with membranous nephropathy--based on
      20 years follow up study].
AB  - It is not certain whether the life expectancy of patients with membranous
      nephropathy is shorter than that of an age-matched healthy population. Forty-one
      patients (21 males, 20 females) aged between 16 and 70 years (average age: 33.3
      years) were followed for 20 years. The patients were divided into two groups:
      group I (n = 18), consisting of patients in whom nephrotic syndrome persisted for
      more than two years or until death, and group II (n = 23), consisting of patients
      except for group I. The non-survival criteria are death or renal death. Twelve
      patients (29.3%) died during the study period. Eight patients belonged to group I
      and 4 to group II. The causes of death in group I patients were end-stage renal
      failure in 3 cases, ischemic heart disease in 1 case, subarachnoid hemorrhage in
      1 case, malignancy in 2 cases, suicide in 1 case, and those in the group II
      patients were pneumonia, malignancy, cerebral softening, and diabetes mellitus,
      respectively. Eight patients who died in group I had a significantly longer
      difference between their actual life span (ALS) and life expectancy (LE) and a
      significantly smaller ratio of ALS to LE than the patients who died in group II
      (ALS-LE: -29.9 +/- 4.5 years in group I vs. -9.0 +/- 6.8 years in group II, p <
      0.05, ALS x 100/LE: 22.5 +/- 8.0% in group I vs. 80.9 +/- 25.2% in group II, p <
      0.05). In group I, the ratio of observed to expected death was 4.76 (95%
      confidence interval, 2.05 to 9.37) and significantly higher than that of the
      control population. In group II, however, the ratio was 1.09 (95% confidence
      interval, 0.30 to 2.80), and the difference from the control population was not
      statistically significant. These results suggest that longstanding nephrotic
      syndrome is associated with a shortened life expectancy in patients with
      membranous nephropathy.

PMID- 8264106
TI  - [Prophylactic use of concentrated antithrombin III preparation in children with
      nephrotic syndrome].
AB  - Decreased plasma level of antithrombin III was assumed to be one of the major
      factors underlying hypercoagulable state in nephrotic syndrome. Concentrated
      antithrombin III preparation was given to 8 children with nephrotic syndrome with
      a plasma antithrombin III activity of less than 70%, to evaluate the effect on
      hypercoagulable state. Plasma antithrombin III activity was elevated to more than
      70% in 7 of 8 children after treatment, while plasma levels of plasmin-alpha 2
      plasmin inhibitor complex and FDP-D dimer were not significantly decreased. One
      patient developed brain infarction after the treatment, suggesting that
      prophylactic administration of concentrated antithrombin III preparation is not
      fully protective against thrombotic complications in nephrotic syndrome.

PMID- 8264107
TI  - [Study on vascular calcification in patients on continuous ambulatory peritoneal
      dialysis (CAPD): special reference to active vitamin D (VD) treatment].
AB  - Cardiovascular complications, such as vascular calcification (VC), have been a
      major concern in patients undergoing chronic dialysis. The pathogenesis of this
      VC has been attributed to the altered calcium and phosphate metabolism, but the
      contributing factors have not been clarified. In order to investigate these
      factors, 38 CAPD patients were divided into two sub-groups according to the
      absence of aortic calcification (Group-A; n = 18) or the presence of aortic
      calcification (Group-B; n = 20). The number of elderly patients was larger and
      the duration of CAPD was longer in Group-B than in Group-A. Calcium and phosphate
      metabolism and serum lipids levels did not differ significantly between groups
      and the number of patients given VD was 8/18 in Group-A and 14/20 in Group-B. In
      order to explore the progression of VC in CAPD patients given long-term treatment
      with VD, 22 patients who were matched for the duration of CAPD were analyzed.
      These were divided into two sub-groups according to whether they were treated
      with VD (Group-C; n = 11) or not treated with VD (Group-D; n = 11). Radiological
      findings (such as the degree of aortic calcification), bone mineral content,
      divalent ions, parathyroid hormone levels and lipid profiles were examined. The
      prevalence of patients with aortic calcification was significantly higher in
      Group-D than in Group-C (7/11 v. s. 2/11, P < 0.05). However, lipids, mineral and
      endocrinological parameters did not differ between the sub-groups. No significant
      difference in the calcium and phosphate balance was observed. The bone mineral
      content revealed no difference between both of the sub-groups. VD administration
      by conventional mode, even without significant suppression of PTH or increase of
      bone mineral content, may enhance vessel calcification in patients on long-term
      CAPD.

PMID- 8264108
TI  - [Two cases of hypercalcemic nephropathy associated with primary
      hyperparathyroidism].
AB  - We present two cases of hypercalcemic nephropathy associated with primary
      hyperparathyroidism. Case 1 is a 37-year-old man who had repeated bone fractures
      and recurrent ureteral stones, which led to the diagnosis of primary
      hyperparathyroidism. Case 2 is a 35-year-old man in whom parathyroid carcinoma
      was discovered because of secondary nephrogenic diabetes insipidus, resulting
      from severe hypercalcemia. Both patients developed mild renal dysfunction during
      the course of hyperparathyroidism. In the renal biopsy materials obtained from
      case 1, the renal interstitium showed chronic inflammatory changes. The tubules
      were partly damaged (focal necrosis). Deposition of calcium was sometimes noted
      within the mitochondria of the tubular epithelial cells. Some glomeruli showed
      glomerular sclerosis. In biopsy materials obtained from case 2 after resection of
      the carcinoma, similar histological features were observed, but tubular atrophy
      and necrosis were advanced. Polyuria and hypercalcemia were ameliorated after
      resection. These findings indicate that severe hypercalcemia might induce tubular
      dysfunction as well as organized changes.

PMID- 8264110
TI  - [Characteristics of 201Tl myocardial SPECT and left ventriculography in patients
      with acute diagonal branch myocardial infarction].
AB  - Characteristics of 201Tl myocardial SPECT and ventriculography were studied in 13
      patients with acute diagonal branch myocardial infarction. Rest 201Tl myocardial
      SPECT and left ventriculography were underwent in chronic phase. In 5 patients
      ECG changes in acute phase were not definite. In 6 patients it was difficult to
      identify the obstructed coronary artery with coronary angiography in acute phase.
      Mean value of maximum CPK was 854 (458-1,774) U/l. It seemed to be difficult to
      diagnose acute diagonal branch myocardial infarction with ECG and/or coronary
      angiography. In all patients defects were noted on 201Tl SPECT. Defects were
      small and noted in the central anterior wall and not in the septum. In 2 patients
      defects were noted at apex. In left ventriculography dyskinetic motion was noted
      in 10 patients; one patient showed apical aneurysm and 3 patients showed anterior
      wall aneurysm. In 3 patients anterior wall showed akinesis. It was concluded that
      201Tl myocardial SPECT were useful for detecting diagonal branch lesion. In case
      of diagonal branch myocardial infarction size of defects were small and defects
      were not noted in the septum, however aneurysmal motion was frequently noted.

PMID- 8264109
TI  - [Rest and stress myocardial perfusion imaging on the same day with two injections
      of 99mTc-tetrofosmin].
AB  - 99mTc-tetrofosmin myocardial perfusion imagings under different protocols were
      performed at rest and stress on the same day. In the stress/rest protocol, the
      exercise study was carried out first, and then the rest one followed. Eight
      patients were involved in the stress/rest protocol. Seven patients were examined
      in the reverse, rest/stress protocol. In any protocols, the injection interval
      was 3 hours, and injection doses in the first and second studies were 370 MBq and
      740 MBq, respectively. Myocardial counts were obtained by placing region of
      interest over the myocardial walls in short axial SPECT images. Based on
      myocardial counts from the first injection and the wash-out rate of tetrofosmin,
      we calculated, at the second imaging, counts caused from the first injection.
      Approximately 20-25% of counts in the second study were found to be caused from
      the residual radiotracer. The residual radiotracers affected the interpretation
      of imagings of two patients we examined: one with marked reversible ischemia
      examined in the stress/rest protocol and the other with mild ischemic change
      examined in the rest/stress one. Our results suggested that some modifications of
      studies, such as the increase in the injection intervals or the reduce of the
      first-to-second dose ratio, might be necessary to conduct the same day protocols.

PMID- 8264111
TI  - [A new graphic method for evaluation of distribution volume on N-isopropyl-p
      [123I]iodoamphetamine (IMP) SPECT].
AB  - We developed a new graphic method using N-isopropyl-p-[123I]iodoamphetamine (IMP)
      and SPECT of the brain, the graph on which all three parameters, cerebral blood
      flow, distribution volume (Vd) and delayed count to early count ratio
      (Delayed/Early ratio), were able to be evaluated simultaneously. The kinetics of
      123I-IMP in the brain was analyzed by a 2-compartment model, and a standard input
      function was prepared by averaging the time activity curves of 123I-IMP in
      arterial blood on 6 patients with small cerebral infarction etc. including 2
      normal controls. Being applied this method to the differential diagnosis between
      Parkinson's disease and progressive supranuclear palsy, we were able to
      differentiate both with a glance, because the distribution volume of the frontal
      lobe significantly decreased in Parkinson's disease (Mean +/- SD; 26 +/- 6 ml/g).
      This method was clinically useful. We think that the distribution volume of 123I
      IMP may reflect its retention mechanism in the brain, and the values are related
      to amine, especially to dopamine receptors and its metabolism.

PMID- 8264112
TI  - [The significance of 201Tl/123I MIBG (metaiodobenzylguanidine) mismatched
      myocardial regions for predicting ventricular tachycardia in patients with
      idiopathic dilated cardiomyopathy].
AB  - 123I-MIBG (MIBG) regional defects in myocardial regions with preserved 201Tl (Tl)
      uptake have been observed in patients with idiopathic dilated cardiomyopathy
      (DCM). To evaluate whether the presence of Tl/MIBG mismatched regions is related
      to the occurrence of ventricular tachycardia (VT), we performed myocardial dual
      SPECT imaging with Tl (111 MBq) and MIBG (111 MBq) in 17 patients with DCM, 11
      (Gp A) with and 6 (Gp B) without VT. Myocardial dual SPECT imaging was performed
      at 15 minutes after and 4 hours after the tracer injection. The regional tracer
      uptake was scored visually in 6 segments of the basal, middle, and apical short
      axial images and in 2 apical segments of the midventricular vertical long-axial
      image by a four-point scoring system (0 = normal, 1 = moderate, 2 = severe and 3
      = complete defect). Then, the severity of tracer maldistributions was assessed by
      the difference between total defect scores (TDSs) of Tl and MIBG (delta TDS). TDS
      was not different between Gps A and B in both Tl and MIBG images. However, delta
      TDS was larger in Gp A than in Gp B (13.5 +/- 6.5 vs. 5.8 +/- 3.0, p < 0.05).
      Also, the number of segments with the mismatched tracer uptake was larger in Gp A
      than in Gp B (12.5 +/- 3.0 vs. 8.3 +/- 1.5, p < 0.01). In the electrophysiologic
      study, we found that the fractionated area corresponded to the mismatched region
      in 3 of 5 patients in Gp A. These results suggest that regional sympathetic
      denervation is a possible factor which provocates VT, and myocardial dual SPECT
      imaging with Tl and MIBG is a useful method for predicting VT in patients with
      DCM.

PMID- 8264113
TI  - [Effect of cigarette smoking on diffuse pulmonary uptake of 99mTc-HM PAO].
AB  - To investigate the clinical significance of pulmonary uptake of 99mTc-HM PAO, we
      studied the effect of cigarette smoking on pulmonary uptake of 99mTc-HM PAO. This
      study included 14 volunteers: 4 nonsmokers and 10 smokers (Brinkmann indexes 544
      +/- 270.8). Following injection of 99mTc-HM PAO into the antecubital vein, time
      activity curve was obtained with the regional activity of one frame/min. for 30
      minutes and 64 x 64 matrices. Characteristics of pulmonary clearance curve,
      described as C(t) = A exp-kt, and lung/liver uptake ratio (Lu/Li index) at 30
      min. after injection were determined, and groups of non-smokers and smokers were
      compared. In smokers, 99mTc-HM PAO clearance was delayed and k was smaller
      significantly. Lu/Li index was also higher in smokers. Brinkmann index correlated
      both with k (r = -0.815, p < 0.01) and Lu/Li index (r = 0.911, p < 0.01). In
      conclusion, the delayed clearance and retention of 99mTc-HM PAO in the lung may
      indicate metabolic disorders of the lung due to cigarette smoking.

PMID- 8264114
TI  - [Usefulness of myocardial imaging by 123I-MIBG in assessment of diabetic
      neuropathy].
AB  - In diabetic patients with autonomic neuropathy, it is suggested that there is a
      reduced uptake of 123I-MIBG in the heart. We compared the difference of
      myocardial 123I-MIBG accumulation between 4 diabetic patients with triopathy and
      6 patients without it. In all 10 patients, coronary angiography and 201Tl imaging
      (rest and 4 hours later) were performed. 123I-MIBG (111 MBq) was administered
      intravenously and its imaging was recorded on 15 minutes and 4 hours after
      injection. In all 4 cases with triopathy, 123I-MIBG imaging showed defect in
      apical and inferior region. In 2 out of 6 cases without triopathy, rapid
      clearance was noticed in apical and inferior region. There was no significant
      stenosis in right coronary artery and no defect in initial and delayed 201Tl
      images in all cases. We concluded that diabetic autonomic neuropathy in the heart
      was prominent in apical and inferior region and 123I-MIBG imaging might be useful
      for the evaluation of degrees in diabetic neuropathy.

PMID- 8264115
TI  - [A new headholder for positron emission tomography].
AB  - We developed a new headholder for the fixation and repositioning of patient head
      in PET study. The device consists of acryl frame and headrest of thermoplastic
      resin. Special gel is placed on the headrest to adapt different shape of occipit
      a in each patient. Individual face mask was made with thermoplastic resin just
      before the PET study and was fixed with the holder using plastic taper. It took
      about 2-3 min to fix the patient head using these system. Immobilization of the
      patient's head during PET study was good. Accuracy of repositioning in the same
      patient was relatively good between separate PET studies.

PMID- 8264116
TI  - [Basic study of CA125 measurement using a newly developed "SD-8729" IRMA kit].
AB  - "SD-8729" is a one-step IRMA kit employing OC125 antibody as 125I-labeled tracer
      and M-11 antibody as an immunoadsorbent. Higher bound-radioactivity to beads was
      observed with shorter incubation time than that of a currently used CA125 IRMA
      kit which employed OC125 antibody both as 125I-labeled ligand and immunoadsorbent
      attached to beads. Almost identical CA125 values were obtained by using two kits.
      The antigenic nature recognized by the M-11 antibody seems substantially
      different from those of 130-22 or 145-9 antibodies recognizing CA130 antigen.

PMID- 8264118
TI  - [Qualitative research in nursing. 2. Varieties and types of qualitative
      methodologies].

PMID- 8264117
TI  - [Qualitative research in nursing. 1. Qualitative research: science or "just"
      scholarship].

PMID- 8264119
TI  - [Qualitative research in nursing. 3. Symposium 1: the selection of
      methodologies].

PMID- 8264120
TI  - [Qualitative research in nursing. 4. Qualitative research in nursing: reflections
      on the state of the art].

PMID- 8264121
TI  - [Qualitative research in nursing. 5. Symposium 2: rigor of the qualitative
      research methodologies].

PMID- 8264122
TI  - [Clinical evaluation of plasma atrial natriuretic polypeptide in patients with
      respiratory failure in pulmonary tuberculosis].
AB  - We previously reported the clinical role of plasma immunoreactive atrial
      natriuretic polypeptide (ANP) and cyclic GMP in patients with respiratory
      diseases, bronchial asthma (BA), chronic pulmonary emphysema (CPE) and pulmonary
      insufficiency induced by pulmonary tuberculosis (TBC). In this study, moreover,
      we divided patients with respiratory failure induced by tuberculosis sequelae
      into two groups, patients with oxygen therapy group [O2 (+) group] or ordinary
      practical treatment group [O2 (-) group], and we evaluated the difference of the
      roles of ANP in two groups and the correlation of ANP and c-GMP with clinical
      findings, blood gas analysis, electrocardiogram, chest roentogen photography and
      spirogram in two groups. In conclusion, the respiratory failure in patients with
      tuberculosis sequelae is compensated by increased cardiac output, and that causes
      the rising of right atrial pressure. These results show, addition to the basic
      effects of ANP, the concentration of plasma ANP is released with relating the
      degree of respiratory failure.

PMID- 8264123
TI  - [Therapeutic efficacy of a benzoxazinorifamycin, KRM-1648, administered in
      various frequencies per week in Mycobacterium intracellulare-infected mice].
AB  - Mice were infected intravenously with M. intracellulare (5.2 x 10(6) CFU/mouse)
      and then were given 0.4 mg of KRM-1648 emulsified in 2.5% gum arabic-0.2% Tween
      80 by gavage, once daily 1, 3 or 6 times per week, from 24h after infection to
      the end of experiment (week 8). Evaluation of the therapeutic efficacy of the
      drug against the infection was done on the basis of incidence and degree of gross
      lung lesions, organ weight (square root of organ (mg)/body (g) x 10), and
      bacterial loads in the lungs and spleen. The lung lesions were not observed in
      all experimental groups at 4 weeks after infection. At 8 weeks after infection,
      the lung lesions observed in all control and solute (2.5% gum arabic-0.2% Tween
      80) control mice, whereas 3 of the 5 mice given KRM-1648, 3 times per week and
      all of 5 mice given KRM-1648, 6 times per week showed no lung lesions. Although
      lung lesions were observed in all mice given KRM-1648 only once per week, the
      degree of the lesions was much more milder in KRM-1648-treated mice than in
      solute control mice. The spleen weight of solute control mice and KRM-treated
      mice differed from each other 4 and 8 weeks after infection, especially in mice
      administered 6 times per week. The CFUs of organisms in the lungs and spleen were
      lower in mice treated with the agent than in mice given solute at 4 and 8 weeks
      after infection, in orders of administration of 6, 3 and 1 times per week.

PMID- 8264124
TI  - [Detection of Mycobacterium intracellulare by PCR].
AB  - PCR products amplified with the primers YNP-1 and YNP-2 and template DNA from
      various mycobacterial species showed differences in molecular sizes. By
      sequencing the PCR products, we found that the DNA fragment from M. tuberculosis
      and that of M. intracellulare have different DNA sequences. The former was 164
      bp, composed of 27 A, 54 C, 57 G, and 26 T, while the latter was 109 bp, composed
      of 22 A, 37 C, 34 G, and 16 T. We compared these sequences and selected a
      nucleotide sequence unique to M. intracellulare and used as primer YNP-7.
      Antisense primer, YNP-8, was constructed from the complementary sequence of YNP-2
      which is located about 270 b downstream of YNP-7. Results of PCR using the
      primers YNP-7 and YNP-8 and template DNA of various mycobacteria showed that
      positive results were only with the template DNA from M. intracellulare.
      Bacterial DNA from those other than mycobacteria but appear in sputum were tested
      in PCR with the primers YNP-7 and YNP-8. None of them showed positive results.
      Specificity of the PCR products was determined with a specific probe MIP which
      was constructed using a sequence between YNP-7 and YNP-8 to confirm the
      specificity of PCR by Southern hybridization. Only the products from M.
      intracellulare hybridized with the probe MIP, indicating the specificity of YNP-7
      and YNP-8 to M. intracellulare.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264125
TI  - [A case of Addison's disease caused by adrenal tuberculosis, and revealed acute
      hypoadrenocorticism].
AB  - We reported a case of Addison's disease, caused by adrenal tuberculosis. The
      patient was female, seventy four years old. She complained cough and body weight
      loss. She complained cough from June, 1989, but her home doctor didn't take care
      of her symptoms. September 1989, she felt appetite loss, and easy fatigue, so her
      home doctor suspected her disease as pulmonary tuberculosis, so he introduced our
      hospital, and she admitted. When she admitted, her chest roentogenogram revealed
      bIII2. Sputum smear examinations were negative. Laboratory data on admission, we
      observed slightly eosinophilia, severe iron deficiency anemia, and accenturation
      of blood sedimentation rate. Immediately after admission, she complained nausea,
      vomiting, coldness, and powerless. On 25 days after admission, she lost her
      senses suddenly, and her blood pressure fell 5 days after, she fell in shock
      state, too. We found out her blood sugar data was 29. After blood examinations,
      we found out that ACTH was high, cortisole, 17-KS, 17-OHCS were low. So we
      thought she got acute hypoadrenocorticism. We found her abdominal CT revealed
      calcification in her right adrenal gland. We diagnosed her disease as Addison's
      disease caused by adrenal tuberculosis so we began to give prednisolone, 7.5 mg
      per day. After giving, her state made better. We thought her disease as Addison's
      disease caused by adrenal tuberculosis, revealed acute hypoadrenocorticism.

PMID- 8264126
TI  - [Advances in diagnostic methods for mycobacteria].
AB  - Two systems, biphasic MB-Check and radiometric BACTEC, based on liquid media
      proved to be significantly better than the egg-based solid media for the
      isolation of mycobacteria from clinical specimens. The difference in the rates of
      isolation of mycobacteria between two groups of media was more remarkable with
      smear-negative specimens. The time to the detection of the Mycobacterium
      tuberculosis complex with MB-Check was shorter than that with the 3% Ogawa egg
      method but longer than that with BACTEC. A total of 135 sputum specimens were
      examined by the polymerase chain reaction (PCR) using oligonucleotides based on
      the repetitive sequence (IS986) of M. tuberculosis as a primer. The PCR gave an
      overall positivity rate of 84.2%, as compared with 71.9% by smear and 96.9% by
      culture in the liquid medium, MB-Check. Although the sensitivity of the PCR
      appeared to be similar to that of culture with the MB-Check system, the PCR
      should be very useful for rapid detection of M. tuberculosis infections. DNA
      probe technology facilitates a rapid and specific identification of
      microorganisms. The diagnostic specificity and sensitivity of the nonradioactive
      Accuprobe M. tuberculosis complex and Accuprobe M. avium complex culture
      confirmation tests were nearly 100%. The results of the colorimetric
      microdilution plate hybridization test (DDH-Mycobacteria) for identification of
      mycobacteria were consistent with those of biochemical identification. About 90%
      of clinical isolates could be identified by the DDH kit. Both of these methods
      may contribute to the rapid diagnosis of mycobacterial infections.
      Epidemiological studies with techniques which allow differentiation of strains
      within M. tuberculosis groups are important for limiting the dissemination of the
      disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264127
TI  - [Progress and application of molecular genetics in the research of Mycobacterium
      tuberculosis].
AB  - In the last decade, a great deal of advances in the genetics of Mycobacterium
      tuberculosis have been made by the introduction of new genetic technologies. In
      this review, a brief discussion of the progress in mycobacterial genetics,
      especially, gene cloning, development of host-vector systems, structural analysis
      of chromosomal DNA, plasmid DNA and mycobacteriophage DNA, IS element, and drug
      resistance mechanism was presented.

PMID- 8264128
TI  - [The immunology of mycobacterial diseases].
AB  - Protection and pathogenesis of tuberculosis greatly depend on specific T
      lymphocytes. Recent evidence suggests the existence of at least two pathways of
      acquired specific resistance to M. tuberculosis infection: The first consists of
      cytokine-mediated activation of infected host cells by protective CD4+ T cells,
      which are currently believed to mediate antimicrobial activity via the release of
      macrophages activating cytokines such as IFN-gamma and TNF-alpha. The second
      involves the lysis of these infected cells by cytotoxic effector CD4+ T cells,
      which is class II MHC restricted, requires cell-to-cell contact mediated by the
      ICAM-1 and LFA-1 ligand pair, and appears to be independent of lymphotoxins and
      through the direct cell interaction by adhesion molecules such as LFA-1 and ICAM
      1 but not cytokines. On the other hands, gamma delta T cells might be part of the
      primary response to infection with live M. tuberculosis. gamma delta T cells have
      the potential to express cytotoxicity for mononuclear phagocytes pulsed with
      mycobacterial antigens, and are capable of secreting a variety of cytokines,
      including IL-2 and IFN-gamma. Intracellular killing mechanisms by activated
      macrophages are still unknown. Recently, increasing attention has been focused on
      the role of NO as a mediator of a number of physiological reaction. Activated
      macrophages appear to exhibit some antimicrobial actions as well as antitumor
      effects via generation of NO, which depends on the L-arginine oxidation pathway.
      However, it is still unknown whether or not human macrophages generate NO
      radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264129
TI  - [Expectation of new antituberculous drugs and targeting therapy for treatment of
      mycobacterial infections].
AB  - Recent AIDS endemic causes the worldwide increase in intractable mycobacterial
      infections including extrapulmonary tuberculosis due to drug resistant organisms
      and disseminated Mycobacterium avium complex infections. Therefore, new
      antituberculous (antimycobacterial) drugs and development of regimens and
      protocols for clinical treatment of such mycobacterial infections are urgently
      needed. Here, I described the present situations of new antituberculous agents,
      in particular new rifamycin derivatives including rifabutin and
      benzoxazinorifamycin (KRM-1648), new macrolides such as clarithromycin and
      azithromycin, and new quinolones including sparfloxacin, ofloxacin,
      ciprofloxacin, fleroxacin, AM-1155 and so on. Their in vitro antimycobacterial
      activities, therapeutic efficacy against experimental infections induced in
      animals especially in mice, and clinical trials using these drugs are summarized
      by referring to recent studies by worldwide investigators including us. Moreover,
      this paper dealt with some of recent attempts for chemotherapy of mycobacterial
      infections employing the drug delivery system using liposomal microvesicles as a
      carrier of drugs. Although these new drugs and development in new regimens
      appreciably potentiated the efficacy of controlling mycobacterial infections, in
      particular M. avium complex infections, it remains very difficult to achieve a
      complete elimination of the organisms from the sites of infection, even if
      provided multi-drug regimens using new drugs having excellent antimycobacterial
      activity and sufficient dosages. Therefore, it seems important to make an effort
      to elucidate the mechanisms of induction of immuno-unresponsiveness in hosts in
      progressed state of mycobacterial infection, as well as to develop new drugs
      possessing more potent antimycobacterial activity.

PMID- 8264130
TI  - Tamm-Horsfall glycoprotein binds IgG with high affinity.
AB  - Tamm-Horsfall protein (THP), a monomeric glycoprotein (M(r) 80 to 100 kDa), is
      produced by the mammalian kidney's thick ascending limb of Henle cells and
      excreted into the urine. The function of THP is uncertain. Here we report that a
      high molecular weight contaminant in sheep THP (sTHP) preparations was identified
      as sheep IgG by its positive reaction with donkey anti-sheep IgG antibody and
      with protein G. To answer the question of whether sTHP and sheep IgG co-purified
      because of a physical interaction between the two proteins, an enzyme-linked
      immunosorbent assay (ELISA) using immobilized sTHP and soluble sheep IgG was
      performed. Analysis of the ELISA data identified the presence of two sets of
      binding sites: a high affinity site (Kd 10(-8) to 10(-9) M) and a lower affinity
      site (Kd 10(-6) to 10(-7) M) [corrected]. The ELISA detected a similar high
      affinity interaction between human THP (hTHP) and human IgG. The binding of sheep
      IgG to immobilized sTHP was inhibited by soluble sTHP. These observations suggest
      an additional factor to be considered in studies addressing THP's potential
      immunoregulatory function.

PMID- 8264131
TI  - Transforming growth factor beta increases the expression of HIV-1 gene in
      transfected human mesangial cells.
AB  - Human immunodeficiency virus type 1 (HIV) infection is often complicated by focal
      glomerulosclerosis (FGS) and other renal lesions collectively termed HIV
      associated nephropathy (HIVAN). FGS is characterized by glomerular mesangial
      expansion and increased synthesis of matrix components. The molecular pathogenic
      mechanisms associated with the development of HIV associated nephropathy are
      unknown. Experimental animal models suggest a role for cytokines and growth
      factors, particularly transforming growth factor beta (TGF-beta), in the
      pathogenesis of glomerulosclerosis. Patients with AIDS have elevated plasma and
      tissue levels of TGF-beta. We carried out experiments to determine whether
      primary human mesangial cells (HMC) in culture can be transfected with HIV-1
      genes. HMC were transfected with a chloramphenicol acetyl transferase (CAT)
      reporter construct containing HIV-1 acetyl transferase (CAT) reporter construct
      containing HIV-1 LTR sequences. Our results show successful transfection of HMC
      with HIV-1 LTR gene. HMC transfected with LTR gene are responsive to the HIV-1
      regulatory gene product Tat. To study whether TGF-beta can modulate the
      expression of HIV-1 LTR gene in HMC, HMC transfected with an HIV-1 LTR CAT
      plasmid were treated with TGF-beta and other growth factors two hours before
      harvest. TGF-beta specifically increased the expression of the HIV-1 gene in HMC
      in a dose dependent manner. We further studied whether up-regulation of HIV-1 LTR
      expression in HMC was mediated by the effect of TGF-beta on the interaction of
      transcription factors to their binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264132
TI  - Stimulated renal tubular epithelial cells induce anergy in CD4+ T cells.
AB  - Renal tubular epithelial cells (TEC) can express MHC class II molecules in vitro
      and in vivo. Their ability to also secrete cytokines and express adhesion
      molecules suggests a possible immune accessory role for TEC. We have previously
      documented that TEC process and present antigen to T cell hybridomas. However,
      engagement of the T cell receptor alone is sufficient to induce IL-2 secretion by
      T cell hybridomas. We now report that presentation of antigen by TEC to a CD4+ T
      cell clone results in functional inactivation of the T cells. Despite antigen
      specific anergy, these T cells are viable and proliferate in response to IL-2.
      Furthermore, allogeneic antigen presenting cells were unable to restore the T
      cell proliferative response, suggesting that the mechanism(s) was not entirely
      costimulator-dependent.

PMID- 8264133
TI  - Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte
      antibody-induced glomerulonephritis.
AB  - The infiltration of monocytes-macrophages in the glomerulus is one of the
      hallmarks of glomerulonephritis and may play an important pathogenetic role.
      Monocyte chemoattractant protein-1 (MCP-1) and colony stimulating factor-1 (CSF
      1) are monocyte-specific cytokines with chemoattractant and activating activities
      for monocytes. MCP-1 and CSF-1 can be generated by several cell types, including
      glomerular mesangial cells, and can be stimulated by cytokines and immune
      complexes. To study the expression of CSF-1 and MCP-1 in a model of proliferative
      glomerulonephritis we used Northern blot analysis and immuno-histochemistry. The
      glomerular lesion was induced in rats by the i.v. injection of a heterologous
      anti-thymocyte antiserum (ATS), directed against an antigen which is localized on
      glomerular mesangial cells. Northern blot analysis revealed comparable amounts of
      CSF-1 in glomeruli isolated from control untreated rats, and from rats after 30
      minutes to three weeks of injection of ATS antibody. In control glomeruli no mRNA
      levels for MCP-1 were detectable, but increased markedly 30 minutes after the
      induction of the nephritis, were then reduced at 24 hours and increased again at
      5 and 21 days after induction of the disease. The increase in mRNA levels for MCP
      1 30 minutes or 24 hours after ATS injection was markedly attenuated if rats were
      complement depleted by cobra venom injection. These time points following
      antibody injection were associated with mesangial immune complex formation (30
      min), mesangiolysis (24 hr) and proliferative glomerulonephritis (5 and 21 days).
      By immunohistology the presence of MCP-1 was demonstrated in glomeruli with a
      predominant mesangial distribution. The mesangial immunofluorescence for MCP-1
      followed a pattern similar to that of the mRNA for MCP-1 after induction of the
      disease process, that is, it increased after 30 minutes, decreased after 24 hours
      and was increased again at three weeks. Within 30 minutes of the antibody
      injection an increased infiltration of monocytes-macrophages was observed in the
      glomeruli, which was maintained up to three weeks of induction of the
      glomerulonephritis. When the rats were decomplemented with cobra venom factor
      prior to the i.v. injection of ATS, the expression of MCP-1 in glomeruli remained
      low and the influx of monocytes/macrophages did not appear. We conclude that MCP
      1 is increased early on in glomeruli of rats with immune-mediated mesangial
      proliferative glomerulonephritis. This increase is mediated by complement
      activation secondary to the in situ immune complex formation at the glomerular
      mesangium.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8264134
TI  - Protein and energy intake, nitrogen balance and nitrogen losses in patients
      treated with continuous ambulatory peritoneal dialysis.
AB  - The aim of this investigation was to analyze factors which influence the dietary
      protein intake (DPI), the energy intake and the utilization of ingested protein,
      and to determine the relationship between various types of nitrogen losses in
      stable continuous ambulatory peritoneal dialysis (CAPD) patients. We performed 23
      nitrogen balance (NB) studies of 6 to 11 days duration in 12 CAPD patients. One
      study was performed in all patients 3.4 +/- 1.2 months after starting CAPD (early
      studies). The study was then repeated in nine patients after 12.1 +/- 2.6 months,
      and two of these patients were studied again after 16 and 24 months, respectively
      (late studies). Before each NB study, the dietary intakes prior to the study were
      assessed in diaries and interviews. During a few days preceding the NB periods
      and during the NB periods each patient received an individualized diet composed
      so as to resemble the patients' spontaneously chosen diet regarding DPI and
      dietary energy intake (DEI). Total nitrogen, protein, urea and creatinine were
      analyzed in the dialysate and urine collected daily. Total nitrogen was also
      analyzed in the feces, collected over the whole NB period. Total nitrogen
      appearance (TNA), non-protein nitrogen appearance (NPNA) and urea nitrogen
      appearance (UNA) were calculated by correcting total nitrogen output, non-protein
      nitrogen output, that is, TNA minus the total protein losses (PL) and urea
      nitrogen output for changes in total body urea nitrogen. Glucose was determined
      in the collected dialysate and the daily glucose absorption was calculated. DPI
      varied between 0.62 and 2.09 g/kg/day, DEI between 21 and 42 kcal/kg/day and the
      peritoneal energy (glucose) intake (PEI) between 4 and 13 kcal/kg/day. DPI (but
      not DEI) correlated with Kt/V(urea) and Kt/VCr and with total and renal
      clearances for urea and creatinine. NB (not corrected for "unmeasured" nitrogen
      losses) was positive in most studies, and it correlated with DPI and the total
      energy intake (TEI) in the early studies, but only with TEI in the late studies.
      DPI correlated with TNA, NPNA, UNA, non-protein-non-urea nitrogen loss and fecal
      nitrogen loss. UNA was highly correlated with TNA and NPNA (r = 0.95). We used
      data from 33 NB studies in CAPD patients (our present data combined with data
      from the literature) to calculate regression equations describing the
      relationship between TNA and NPNA, respectively, and UNA.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8264135
TI  - The renal clearance and infusion clearance of inulin are similar, but not
      identical.
AB  - Thirty-eight simultaneous renal (R-Cin) and infusion (INF-Cin) clearances of
      inulin were done. The equilibration period preceding the clearance studies was of
      at least two hours duration. The R-Cin on each subject was based on two clearance
      periods during which the plasma inulin concentration ([P(in)]) varied by 1.0
      mg/dl or less and the rate of inulin excretion by less than 10%. There was
      excellent correlation between the R-Cin and the INF-Cin (r = 0.976), but the INF
      Cin consistently exceeded the R-Cin (mean difference = 13.8 +/- 8.8 ml/min/1.73
      m2, t = 9.7163 and P = < 0.001). Complete equilibration of inulin in body fluids
      has been assumed when [P(in)] levels were relatively constant (variation < 10%).
      However, complete equilibration of inulin would not be present, even with
      relatively constant P(in) levels, if the rate of infusion of inulin were equal to
      the rate of excretion plus the rate of penetration of inulin into less permeable
      components of the extracellular fluid compartment (that is, dense connective
      tissue solids). Estimation of glomerular filtration rate using the INF-Cin
      requires complete equilibration of inulin in body fluids, a process probably
      requiring 12 to 15 hours or longer.

PMID- 8264136
TI  - Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance
      hemodialysis patients with/without diabetes mellitus.
AB  - We studied the quantitative and qualitative characteristics of lipoprotein(a)
      [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients
      (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without
      diabetes mellitus (DM), in 101 patients with diabetes mellitus without
      hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88
      females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients
      than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD
      without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in
      controls, respectively). Apo(a) phenotyping was performed by a sensitive, high
      resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal
      controls, the molecular weights of apo(a) isoforms were inversely correlated with
      plasma Lp(a) levels, and the same tendency was found in patients who were
      undergoing hemodialysis and/or who had diabetes mellitus. We assumed the
      differences in apo(a) phenotypes detectable with our method reflected consecutive
      differences in molecular weights of apo(a). The results of an analysis of
      covariance and a least square means comparison indicated that the regression
      lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient
      groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as
      compared to the regression line of the control group. Even after the low
      molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was
      observed. However, no differences were observed between the patient
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264137
TI  - Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology
      in end-stage renal disease.
AB  - We analyzed transiliac bone biopsy specimens from 30 end-stage renal failure
      patients, taken at the time of admission for CAPD training. Results were compared
      with values of iPTH, bone alkaline phosphatase, 1,25-dihydroxyvitamin D3,
      skeletal survey, quantitative computed tomography (QCT) and single photon
      absorptiometry (SPA) bone density measurements. Osteitis fibrosa was the most
      common histological diagnosis, present in 15 of the 30 patients (50%), with eight
      classified as "severe" and seven as "mild." Eight patients (27%) had adynamic
      bone lesion, four mixed renal osteodystrophy (13%), and two (7%) osteomalacia.
      The mean age of the adynamic group was higher than the osteitis fibrosa group (41
      +/- 12.1 vs. 56 +/- 10.2 years; P < 0.01), and than the mixed group (39 +/- 7.5
      vs. 56 +/- 10.2 years; P < 0.02). Levels of iPTH enabled discrimination between
      groups, but not between individual patients, and values correlated with bone
      alkaline phosphatase (r = 0.62; P < 0.001). Erosion of the terminal phalanges was
      seen on the plain X-rays of 7 of 15 patients with mild or severe OF, and in three
      patients with another diagnosis. The majority of patients (> 90%) had bone
      density measurements within the normal range. No significant correlation existed
      between QCT or SPA scores and any of the histomorphometric parameters, or iPTH.
      We conclude that iPTH is the most helpful non-invasive investigation in this
      group of patients. Plain X-ray of the hands is the most useful radiological
      investigation, but single measurements of bone density are not diagnostic.

PMID- 8264138
TI  - Effect of an increased intraperitoneal pressure on fluid and solute transport
      during CAPD.
AB  - The effect of an increased intraperitoneal pressure on fluid and solute transport
      was studied in eight stable CAPD patients. Two permeability tests of two hours
      each with continuous registration of the intraperitoneal pressure were performed
      while patients were in supine position. The intra-abdominal pressure was raised
      by means of a tightening girdle with inflatable cuffs in one of the experiments.
      Intraperitoneally administered dextran 70 was used as a volume marker in order to
      determine the peritoneal fluid kinetics. The increment in the intra-abdominal
      pressure of 10.0 +/- 1.0 mm Hg caused a decline in the net ultrafiltration. This
      was mainly determined by an increase in the lymphatic absorption: 1.07 +/- 0.18
      ml/min (without compression) versus 1.86 +/- 0.25 ml/min (with compression; P <
      0.01), whereas the transcapillary ultrafiltration rate tended to decrease: 2.02
      +/- 0.23 versus 1.73 +/- 0.27 ml/min (P = 0.08). External compression also
      diminished solute transport from the circulation to the peritoneal cavity. The
      decline in the mass transfer area coefficient of urea, creatinine, urate and beta
      2-microglobulin was 13%, indicating a smaller effective peritoneal surface area
      caused by external compression probably due to a decrease in the number of the
      perfused peritoneal capillaries. The fall in the peritoneal protein clearances
      was more pronounced the higher the molecular weight of the protein, consistent
      with a decline in the intrinsic permeability of the peritoneum. Kinetic modeling
      using computer simulations was used to analyse these effects in terms of the pore
      theory, using a convection model (large pore radius 184 +/- 14 A) and a diffusion
      model (large pore radius 1028 +/- 218 A) for the transport of
      macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264139
TI  - Evidence for high risk of cerebral hemorrhage in chronic dialysis patients.
AB  - One-half of the total deaths in chronic dialysis patients are due to
      cardiovascular disease; however, the precise incidence and relative risk of those
      compared to normals are not known. Therefore, we sought to determine the annual
      incidence of cardiovascular disease and relative risk of those on chronic
      dialysis to the general population. Both the general population (1.2 million,
      Census 1990) and chronic dialysis patients (N = 1,609) in Okinawa, Japan were
      studied prospectively from April, 1988, to March, 1991. Diagnosis of stroke was
      made by symptoms and brain CT scan, and acute myocardial infarction was done by
      changes in electrocardiogram and serum enzymes. The relative risk
      (observed/expected ratio) was calculated by using the standardized morbidity rate
      obtained in both sexes and age-class every 10 years in the general population.
      Forty-one stroke (8 cerebral infarction, 31 cerebral hemorrhage, and 2
      subarachnoid hemorrhage) and four acute myocardial infarction cases were
      registered during the study period in chronic dialysis patients. The incidence
      per 1,000 person-year was 11.5 in stroke, 2.2 in cerebral infarction, 8.7 in
      cerebral hemorrhage, 0.6 in subarachnoid hemorrhage, and 1.1 in acute myocardial
      infarction. The relative risk compared to normals was 5.2 in stroke, 2.0 in
      cerebral infarction, 10.7 in cerebral hemorrhage, 4.0 in subarachnoid hemorrhage,
      and 2.1 in acute myocardial infarction. Cerebral hemorrhage occurred at 10 years
      younger than that of the general population (P < 0.001) and was associated with
      high prevalence of hypertension and low levels of serum albumin and cholesterol.
      Our results confirm the importance of blood pressure control and nutritional
      status in chronic dialysis patients.

PMID- 8264140
TI  - Identification of a single base insertion in the COL4A5 gene in Alport syndrome.
AB  - We identified a novel mutation in the COL4A5 gene of a Japanese patient with
      Alport syndrome. A combination of in vitro amplification of the exons with single
      strand conformation polymorphisms (SSCP) analysis suggested the presence of a
      mutation in exon 48. Sequencing of the amplified DNA revealed a single base (T)
      insertion which was between nucleotides T 4750 and G 4751 within the methionine
      1516. This mutation caused a shift in the reading frame of nine amino acids and
      introduced a premature termination signal that would be expected to lack about
      two-thirds of the noncollagenous (NC1) domain. This mutation may interfere with
      type IV collagen assembly leading to increased permeability and play a causative
      role in the glomerular basement membrane abnormality of this patient with typical
      Alport syndrome. Gene tracking by restriction enzyme NlaIII digestion revealed
      that the patient's mother is heterozygous whereas the patient's brother and one
      sister are normal, albeit they have hematuria and proteinuria. Without gene
      analysis, they would have been misdiagnosed. We propose that the diagnosis of
      Alport syndrome should be made on the basis of both clinical phenotypes and
      molecular defects.

PMID- 8264141
TI  - Hepatitis C virus RNA in anti-HCV positive hemodialyzed patients: significance
      and therapeutic implications.
AB  - About 25% of French hemodialysis patients have antibodies against the hepatitis C
      virus (HCV), which may reflect either past or active HCV infection. It is
      important to evaluate the significance of these antibodies, as most hemodialysis
      patients are candidates for kidney transplantation and have normal transaminase
      activities despite biopsy-proven chronic hepatitis. We prospectively assayed HCV
      viremia with the nested polymerase chain reaction in 61 patients on maintenance
      hemodialysis who had anti-HCV antibodies detectable in second generation tests
      (ELISA2 or RIBA2). HCV RNA was repeatedly detected in the serum of 52 (85.2%)
      patients. Liver biopsy, which was performed in 17 cases, revealed chronic
      hepatitis in 16 cases (including 2 of cirrhosis) and steatosis in one.
      Hypertransaminasemia was observed in only 31.3% and 30.8% of patients with
      chronic hepatitis and HCV viremia, respectively. Anti-HCV antibodies are
      frequently associated with HCV viremia, resulting usually in chronic hepatitis,
      although hypertransaminasemia is uncommon. HCV viremia reflects both post
      transfusional and community-acquired HCV infection. These findings suggest a need
      for liver biopsy and antiviral treatment before kidney transplantation. The
      isolation of anti-HCV positive subjects in the dialysis setting should be
      evaluated to reduce patient-to-patient transmission of HCV.

PMID- 8264142
TI  - Autosomal dominant polycystic kidney disease in Toronto.
AB  - This study describes the Toronto, Ontario experience with autosomal dominant
      polycystic kidney disease (ADPKD). Patients were divided into three groups: Group
      1, 19 families studied with genetic markers; Group 2, 80 pre-dialysis ADPKD
      patients followed by Toronto nephrologists in whom the incidence of non-renal
      complications and the mean age of onset of symptomatology is documented; Group 3,
      4,449 individuals who entered end-stage renal failure (ESRF) in the Toronto
      region between the years 1981 and 1992, 320 with ADPKD and 4129 with other
      diseases. In this third group age of onset of ESRF, frequency, age and cause of
      death is compared between ADPKD and non-ADPKD. ADPKD caused by a gene different
      from that linked to chromosome 16 short-arm probes occurred at a frequency of
      between 8 and 17%. Incidence of hepatic cysts in ADPKD was similar to that of
      previous series, other organ involvement was underdiagnosed without deliberate
      screening, and incidence of symptomatic intracranial aneurysm was 1.25%. A 5%
      excess of patients with ADPKD died of cerebro-vascular accident. Years of
      survival after ESRF measured by life table analysis was significantly greater for
      ADPKD patients than for non-ADPKD patients. A high frequency of death due to
      infection still exists in ADPKD despite the reduction of invasive procedures in
      diagnosis and treatment, and despite the presumably improved recent methods of
      managing infection. The average age of onset of ESRF has been delayed by over six
      years, and average age of death of ADPKD patients at 63.9 years-old by 12.4 years
      since 1960.

PMID- 8264143
TI  - Effects of rHuEPO on Q-EEG and event-related potentials in chronic renal failure.
AB  - Quantitative electroencephalography is a powerful tool to evaluate brain
      function, and preliminary data have shown its usefulness in the evaluation of
      patients with chronic renal failure (CRF). In this study, baseline values of
      different quantitative EEG variables, as well as data from the P300 component of
      the visual event-related potential, in 43 patients with chronic renal failure,
      were compared with those of a group of healthy subjects and with the results
      obtained after 3, 6, 9 and 12 months of treatment of these patients with rHuEPO.
      Baseline total power was much lower in patients with CRF than in healthy
      subjects, and the distribution of power among the frequency bands was also
      abnormal. rHuEPO promptly normalized total power and progressively improved power
      distribution, although full normality was not achieved. Mean dominant frequencies
      in brain areas were abnormal in patients with CRF, and progressive improvement
      was seen along the study. The latency of P300, which was increased before
      treatment, decreased in all subjects, but normal values were not reached. The
      same applies to the hypomanic and psychopathic scores of psychological tests.
      Altogether, brain dysfunction of CRF seems to substantially improve by treatment
      of the anemia with rHuEPO.

PMID- 8264144
TI  - Lipoprotein(a) in nephrotic syndrome.
AB  - Lipoprotein(a) [LP(a)] is an independent risk factor for cardiovascular disease,
      and it has also been speculated that it promotes thrombosis. Recent studies have
      shown that patients with gross proteinuria have greatly increased plasma levels
      of Lp(a), but the genesis is obscure. In the present study, plasma Lp(a) levels
      were measured in 31 patients with nephrotic syndrome (NS), 24 patients with IgA
      nephropathy and 43 healthy control subjects. Lp(a) levels were significantly
      elevated in NS (median 49.0 mg/dl), in contrast to the control subjects and
      patients with IgA nephropathy (median 7.0 and 9.7 mg/dl, respectively). Plasma
      Lp(a) levels fell markedly in 10 of 10 NS patients after remission. In NS, Lp(a)
      levels correlated directly with serum cholesterol levels (P < 0.05) and
      indirectly with plasma orosomucoid levels (P < 0.05), but not with serum albumin,
      triglycerides, HDL cholesterol, urinary protein excretion or GFR. In addition,
      Lp(a) tended to be higher in NS patients with edema (median 54.3 mg/dl) than in
      patients without edema (19.0 mg/dl; P = 0.06). Nine NS patients were further
      evaluated with plasma ANP levels and urinary sodium excretion. Plasma Lp(a)
      correlated directly with ANP (P < 0.01) and indirectly with urinary sodium
      excretion (P < 0.05). Excellent correlations were found between Lp(a) and VLDL
      cholesterol and VLDL triglycerides, respectively, suggesting a close link between
      Lp(a) and triglyceride-rich lipoproteins in nephrosis.

PMID- 8264145
TI  - Simvastatin therapy for hypercholesterolemic patients with nephrotic syndrome or
      significant proteinuria.
AB  - Experimental evidence suggests that lipid lowering therapy could slow the
      progression of renal disease in humans. We have conducted a double-blind, placebo
      controlled trial of the HMG CoA reductase inhibitor simvastatin in patients with
      the nephrotic syndrome or significant proteinuria (> 1 g/day) and
      hypercholesterolemia (> or = 6.5 mmol/liter). Patients were placed on a lipid
      lowering diet for at least 10 weeks before randomization. After a four-week
      placebo run-in, 30 adults were randomized to simvastatin or placebo therapy (10
      mg/day, increasing to 20 to 40 mg/day as required) for 24 weeks. There were seven
      dropouts, none of whom were "definitely" related to drug therapy. Total and LDL
      cholesterol levels fell by a mean of 33 and 31%, respectively, in simvastatin
      treated patients, compared with only 5 and 1% in patients on placebo (P < 0.001,
      P = 0.002, respectively). Apolipoprotein B100 levels fell by a mean of 31% in the
      simvastatin group but rose 0.3% in the placebo group (P = 0.014). There were no
      significant changes in HDL levels. There were no significant differences between
      the groups in their urine protein levels, their rise in plasma creatinine, or
      decline in plasma inulin clearance. Simvastatin is a safe, effective therapy for
      hypercholesterolemia in proteinuric states. A much larger trial is needed to show
      if potent lipid-lowering therapy slows progression of hypercholesterolemic
      proteinuric diseases.

PMID- 8264146
TI  - Role of glucocorticoid in excretion of an acute potassium load in patients with
      Addison's disease and panhypopituitarism.
AB  - Glucocorticoid (GC) has been shown to stimulate potassium (K) excretion in
      various conditions, but it is still incompletely resolved whether its presence is
      essential for the normal K homeostasis. We addressed this question in patients
      with selective GC deficiency (panhypopituitarism) and with combined GC and
      mineralocorticoid deficiency (Addison's disease), studied 24 hours after
      withdrawal of their regular substitution therapy. Compared to data in healthy
      subjects, both basal K excretion and the kaliuresis after a KCl load (1 mmol/kg
      body wt orally) were impaired in either patient group (P < 0.05). Physiological
      cortisol supplementation (20 mg 3 hr prior to test, and 1 mg/hr during test)
      increased basal K excretion (from 10.6 +/- 1.8 to 19.2 +/- 1.9 mmol/5 hr, P <
      0.01) and KCl stimulated kaliuresis (from 47.9 +/- 6.1 to 54.8 +/- 4.7 mmol/5 hr,
      P = 0.06) to normal levels in panhypopituitarism. Cortisol also improved basal K
      excretion (from 10.2 +/- 1.5 to 16.9 +/- 3.5 mmol/5 hr, P < 0.05) and KCl
      stimulated K excretion (from 31.6 +/- 2.5 to 45.2 +/- 3.8 mmol/5 hr, P < 0.05) in
      Addison's disease, although KCl-stimulated K excretion remained below normal (P <
      0.01). The effects of cortisol on sodium excretion differed between the two
      patient groups (P < 0.05) in that only in Addison's disease the improved K
      excretion was associated with sodium retention. Additional experiments with the
      purely GC compound dexamethasone (0.5 mg 3 hr prior to test, and 0.03 mg/hr
      during test) in the patients with Addison's disease also improved K excretion (P
      < 0.05), but without the concomitant sodium retention observed after
      cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264147
TI  - Does prolonged protein restriction preceding dialysis lead to protein
      malnutrition at the onset of dialysis?
AB  - It has recently been suggested that prolonged protein restriction preceding
      dialysis may induce protein malnutrition and thus confer a poor prognosis during
      dialysis. We examined the records of all patients who were prescribed a very low
      protein diet (0.3 g/kg ideal body weight) plus supplemental essential amino acids
      and/or ketoacids for 6 to 72 months (median 26 months) preceding renal
      replacement, numbering 43. Hypoalbuminemia immediately preceding dialysis was
      present in only two patients. Final serum albumin averaged 4.1 +/- 0.4 (SD) g/dl.
      Final transferrin was subnormal in eight patients, but had been subnormal in six
      of these, without attendant hypoalbuminemia, for one to four years. Mean final
      transferrin was 241 +/- 56 mg/dl. Final serum cholesterol was below 150 mg/dl in
      six subjects, all of whom had normal levels of albumin (mean 4.0 +/- 0.2 g/dl)
      and a normal mean value for transferrin (211 +/- 22 mg/dl). In five patients who
      exhibited subnormal albumin and transferrin and high cholesterol concentrations
      at the beginning of dietary therapy, albumin and transferrin levels rose to
      normal or nearly normal, and hypercholesterolemia receded during the ensuing four
      months. Thus this predialysis dietary regimen, rather than causing protein
      malnutrition, prevents it; when protein malnutrition is present, this regimen
      corrects it.

PMID- 8264148
TI  - Prediction of glomerular filtration rate from serum creatinine concentration in
      advanced chronic renal failure.
AB  - In 85 patients with established chronic renal failure, as manifested by serum
      creatinine concentration ([Cr]) > 0.177 mM (> 2 mg/dl), urinary clearance of
      99mTc-DTPA (GFR) and [Cr] were determined one to four times and averaged. GFR was
      expressed per 3 m2 of height2 rather than in terms of 1.73 m2 of surface area
      because weight changes but height does not. GFR in these patients averaged 13
      ml/min/3 m2 (range 2 to 37). The following equations were derived for predicting
      GFR from [Cr]-1 (mM-1), age (years) and weight (kg): males, GFR = 7.57 [Cr]-1 -
      0.103 age + 0.096 weight - 6.66; females, GFR = 6.05 [Cr]-1 - 0.08 age + 0.08
      weight - 4.81. These equations predict GFR in this series with a root mean square
      error of 3.0 ml/min and account for 89% of the observed variation in GFR. They
      are applicable only to patients with [Cr] > 0.177 mM (2 mg/dl). More precise
      estimates can be obtained by including a value for 24-hour urinary urea N, as a
      measure of protein intake. Less precise but simpler estimates can be obtained
      from [Cr]-1 alone: males, GFR = 7.58 [Cr]-1 - 4.29; females, GFR = 6.11 [Cr]-1 -
      3.8. Expressing [Cr] in mg/dl, the latter equations become: males, GFR = 86 [Cr]
      1 - 4.29; females, GFR = 69 [Cr]-1 - 3.8.

PMID- 8264149
TI  - Identification of the renal erythropoietin-producing cells using transgenic mice.
AB  - Regulation of erythropoietin production by the kidneys is central to the control
      of erythropoiesis. Uncertainty about the identity of the renal cells involved has
      been a major obstacle to understanding this mechanism. We have used sequence from
      the mouse erythropoietin locus to direct expression of a marker gene, SV40 T
      antigen, to these cells in transgenic mice. The transgenic constructs contained
      an oligonucleotide marker (Epo-M) or SV40 sequence (Epo-TAg) in the 5'
      untranslated region of the mouse erythropoietin gene, flanked on each side by 9
      and 7.5 kb of DNA from the mouse erythropoietin locus. Anemia-inducible
      expression of Epo-M and Epo-TAg was observed in the kidney. In one of thirteen
      lines, homologous integration of Epo-TAg into the mouse erythropoietin locus
      occurred. In transgenic mice bearing Epo-TAg at homologous and heterologous
      insertion sites, renal expression was restricted to a population of cells in the
      interstitium of the cortex and outer medulla. Immunohistochemical
      characterization by light and electron microscopy shows that these are the
      fibroblast-like type I interstitial cells.

PMID- 8264150
TI  - Renin profiling for diagnosis, risk assessment, and treatment of hypertension.

PMID- 8264151
TI  - Is immunologic tolerance of self modulated through antigen presentation by
      parenchymal epithelium?

PMID- 8264152
TI  - Modulation of phospholipase A2 activity and sodium transport by angiotensin-(1
      7).
AB  - Angiotensin II (Ang II) receptors are coupled to a variety of signal transduction
      mechanisms. In the kidney, Ang II at nanomolar concentration binds to proximal
      tubular cells and stimulates phospholipase A2 (PLA2), which in turn catalyzes the
      hydrolysis of phosphatidylcholine into lysophosphatidylcholine (LPC) and fatty
      acid. This signal transduction pathway has been shown to be an important
      modulator of sodium transport. The kidney cortex possesses the enzyme necessary
      to convert angiotensin I (Ang I) directly to Ang-(1-7) bypassing Ang II as an
      intermediate. The present investigation was undertaken to determine whether Ang
      (1-7) influences epithelial cell function by comparing this heptapeptide with Ang
      II as a modulator of PLA2 activity and sodium transport. Proximal tubular cells
      were labeled in tissue culture with 3H-choline and PLA2 activity was measured by
      quantitation of LPC. We found that Ang II (10(-9) M to 10(-6) M) significantly
      increased PLA2 activity (154 +/- 36% to 209 +/- 94%). Similar results were
      obtained with Ang-(1-7) (240 +/- 130% to 353 +/- 40%). The bioactivity of the
      peptides was assayed by its ability to regulate transcellular 22Na flux. Ang II
      (10(-9) M) inhibited 22Na flux by 12 +/- 2% while Ang-(1-7) (10(-9) M) inhibited
      22Na flux by 20 +/- 5%. These results suggest that one potential role of Ang-(1
      7) in the regulation of kidney epithelial electrolyte transport may involve
      activation of PLA2.

PMID- 8264153
TI  - Biologic and physical characteristics of the non-peptidic, non-digitalis-like
      natriuretic hormone.
AB  - At least three independent groups of natriuretic hormones have been isolated over
      the past ten years. Two, atrial natriuretic factor (ANF) and brain natriuretic
      peptide (BNP), are proteins and the third is made up of digitalis-like substances
      (DLS). The present report concerns the isolation, substantial purification and
      biologic actions of an entirely different natriuretic hormone (NH) which appears
      to be steroidal in nature and an isomer of cortisone. The source of NH was uremic
      urine. Purification involved successive chromatographic steps including gel
      filtration and multiple HPLC runs through C-18 resins. A translucent crystal
      ultimately was obtained. The product was examined using mass spectroscopy with
      trimethylsilyl derivatization. Only one compound was identifiable. The
      characteristics of the molecule include: a molecular weight, 360.4; a molecular
      formula, C21H28O5; a steroidal nucleus; UV absorption at 220 and 290 nm; and
      intrinsic fluorescence. The onset of action occurs within minutes both in the rat
      and, as previously shown, in several in vitro systems including the frog skin,
      toad bladder, fibroblasts and renal tubular epithelial cells grown in culture and
      isolated perfused cortical collecting tubules. In contrast to DLS, NH has been
      previously shown not to cross react with digoxin antibodies. Moreover, when given
      to intact rats, it produces a profound natriuresis but little or no kaliuresis.
      In contrast to ANF and BNP the compound is active orally as well as
      intravenously. It is clearly different from cortisone, based both on its biologic
      and mass spectroscopic characteristics.

PMID- 8264154
TI  - Rat mesangial cell hypertrophy in response to transforming growth factor-beta 1.
AB  - Central features of progressive glomerular sclerosis are initial glomerular
      hypertrophy and subsequent accumulation of extracellular matrix proteins. Since
      TGF-beta 1 may play a key role in this glomerular response to injury, the present
      study sought to explore further TGF-beta 1 actions and regulated expression of
      its receptor in rat mesangial cells. The rat TGF-beta type II receptor (TGF-beta
      RII) homolog was cloned by screening a rat kidney cDNA library with a human TGF
      beta RII cDNA probe, and sequenced. Expression of this receptor subtype in rat
      mesangial cells was then demonstrated by RNase protection assay, and by Northern
      blot analysis of poly (A)+ RNA, TGF-beta RII expression was down-regulated in
      cells treated with exogenous TGF-beta 1. Affinity cross linking studies
      demonstrated presence of this receptor on cell surface. Rat mesangial cells also
      expressed TGF-beta 1 and autoinduction by TGF-beta 1 was observed in the same
      cells, suggesting that this polypeptide may act in an autocrine fashion on
      mesangial cells, and that it may stimulate a positive autoamplification loop. TGF
      beta 1 inhibited mesangial cell proliferation and stimulated significant overall
      protein and collagen production. Furthermore, mesangial cell size increased in
      response to chronic TGF-beta 1 treatment. These findings demonstrate that rat
      mesangial cells express key components of the TGF-beta system and raise the
      intriguing possibility that in the glomerular mesangium, TGF-beta 1 may not only
      induce extracellular matrix synthesis, but may also participate in the process of
      glomerular hypertrophy in response to injury.

PMID- 8264155
TI  - Human mesangial cells and peripheral blood mononuclear cells produce vascular
      permeability factor.
AB  - Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF) is
      a disulfide-linked dimeric glycoprotein of about 40 kD that promotes fluid and
      protein leakage from blood vessels. Various human tumor cell lines and cells
      including fetal vascular smooth muscle cells produce VPF/VEGF. Since glomerular
      mesangial cells (MC) are closely related to vascular smooth muscle cells, we
      examined whether cultured human MC produce VPF/VEGF. Northern blotting analysis
      revealed that cultured human MC expressed a 3.7 kilobases (kb) VPF/VEGF mRNA.
      Human peripheral blood mononuclear cells (PBMC) also expressed VPF/VEGF
      transcripts of 8.6 and 3.8 kb. Although the sizes of the transcripts suggested
      the existence of unique molecular species of VPF/VEGF mRNA in PBMC, RT-PCR
      analysis revealed that PBMC as well as human MC expressed 121, 165, and 189 amino
      acid-containing isoforms of VPF/VEGF, implying that there are no unique
      alternative splicing products of VPF/VEGF mRNA in PBMC. Fetal calf serum and 12-o
      tetradecanoyl- phorbol-13-acetate (TPA) transiently enhanced VPF/VEGF mRNA
      expression in cultured human MC. Transforming growth factor-beta 1 enhanced
      VPF/VEGF mRNA expression in cultured human MC at least within 24 hours.
      Dexamethasone (DEX) inhibited the TPA-induced increase in VPF/VEGF mRNA
      expression, whereas DEX did not change the basal level. The DEX depressed the TPA
      induced increase in VPF/VEGF mRNA expression is therefore probably a result of
      transcriptional control. VPF/VEGF protein was detected in cultured human MC with
      immunoperoxidase staining using anti-VPF/VEGF antibody. TPA increased VPF/VEGF
      protein levels as well as those of VPF/VEGF mRNA in cultured human MC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8264156
TI  - Modulation of antibody-mediated glomerular injury in vivo by interleukin-6.
AB  - We have shown previously that pretreatment with small doses of bacterial
      lipopolysaccharide (LPS), human recombinant interleukin-1 beta (hrIL-1 beta) and
      human recombinant tumor necrosis factor-alpha (hrTNF) increase injury in the
      heterologous phase of nephrotoxic nephritis (NTN). All three pretreatments induce
      synthesis of interleukin-6 (IL-6) which in some systems down-regulates synthesis
      of IL-1 and TNF. We have now investigated the influence of IL-6 on injury in both
      heterologous and autologous phases of NTN in rats. Injection of hrIL-6 in doses
      sufficient to induce hepatic synthesis of acute phase proteins (assessed by
      plasma alpha 2-macroglobulin concentration) had no effect on glomerular injury in
      the heterologous phase of NTN (albuminuria in NTAb alone 9 +/- 6; LPS/NTAb 34 +/-
      10 and IL-6/NTAb 2 +/- 1 mg/24 hr, P < 0.001, Wilcoxon test). In contrast, IL-6
      pretreatment partially abrogated the effect of LPS on albumin excretion (NTAb 4
      +/- 2; LPS/NTAb 85 +/- 11 and IL-6/LPS/NTAb 32 +/- 6 mg/24 hr, P < 0.002),
      percentage of glomerular capillary thrombi (3 +/- 1%; 39 +/- 8%; and 6 +/- 1%, P
      < 0.001) and glomerular neutrophil infiltrate (29 +/- 3; 58 +/- 5; and 34 +/- 2
      neutrophils/50 glomeruli in section, P < 0.001, respectively) at 24 hours. The
      effect of IL-6 was also evident four hours after induction of nephritis and was
      associated with a marked reduction in glomerular concentration of mRNA for IL-1
      beta and TNF, without change in that of tubulin. Serum TNF concentrations were
      also significantly reduced at four hours in IL-6 treated rats.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8264157
TI  - Cyclosporin A inhibits apical secretory K+ channels in rabbit cortical collecting
      tubule principal cells.
AB  - We used the cell-attached patch clamp configuration to examine the effect of
      basolateral cyclosporin A (CsA) exposure on low conductance K+ channels found in
      the principal cell apical membrane of rabbit cortical collecting tubule (CCT)
      primary cultures. Baseline K+ channel activity, measured as mean NPo (number of
      channels x open probability), was 2.7 +/- 1.1 (N = 29). NPo fell by 69% (0.84 +/-
      0.32; N = 32) in cultures pretreated with 500 ng/ml CsA for 30 minutes prior to
      patching. Chelation of intracellular [Ca2+]i (10 mM BAPTA/AM; N = 8) or removal
      of extracellular Ca2+ (N = 9), but not prevention of [Ca2+]i store release (10
      microM TMB-8; N = 7), abolished CsA-induced inhibition. This suggested that CsA
      effects were mediated by an initial rise in [Ca2+]i via Ca2+ influx. Either 25 nM
      AVP (N = 10) or 0.25 microM thapsigargin (N = 8) (causing IP3-dependent and 
      independent release of [Ca2+]i stores, respectively) augmented, while 25 pM (N =
      6) or 250 pM AVP (N = 8) reversed CSA-induced channel inhibition. Apical membrane
      protein kinase C (PKC) activation with 0.1 microM phorbol ester, PMA (N = 8) or
      10 microM synthetic diacylglycerol, OAG (N = 7), mimicked (mean NPo = 0.99 +/-
      0.40) the inhibitory effect of CsA. Apical PKC inhibition by prolonged apical
      exposure to PMA (N = 10) or 100 microM D-sphingosine (N = 6) blocked CsA's
      effect. Cyclic AMP increasing maneuvers, 10 microM forskolin (N = 5) or 0.5 mM db
      cAMP (N = 8), stimulated basal K+ channel activity in the absence of CsA. IN
      CONCLUSION: (1) basolateral exposure to CsA inhibits the activity of apical
      membrane 13 pS channels responsible for physiologic K+ secretion in rabbit CCT
      principal cells. (2) The inhibition is mediated by changes in intracellular Ca2+
      and activation of apical PKC. (3) Pharmacologic AVP (nM) augments CsA-induced
      inhibition by releasing intracellular Ca2+ stores; more physiologic AVP (pM)
      attenuates channel inhibition, probably through cAMP generation. (4) Inhibition
      of apical secretory K+ channels by CsA likely contributes to decreased kaliuresis
      and clinical hyperkalemia observed in patients on CsA therapy.

PMID- 8264158
TI  - Quantification and parametric imaging of renal cortical blood flow in vivo based
      on Patlak graphical analysis.
AB  - Patlak graphical analysis was applied to quantify renal cortical blood flow with
      N-13 ammonia and dynamic positron emission tomography. Measurements were made in
      a swine model of kidney transplantation with a wide range of normal and abnormal
      renal blood flows (N = 57 studies) and in 20 healthy human volunteers (N = 45
      studies). Estimates of renal cortical blood flow by the Patlak method were
      compared to those from a two-compartment model for N-13 ammonia. In addition,
      estimates of renal cortical blood flow by the N-13 ammonia PET approach were
      compared in 10 normal human volunteers to estimates by the metabolically inert,
      freely diffusible O-15 water and a one-compartment model. Patlak graphical
      analysis estimates of renal cortical blood flow correlated linearly with the
      standard two-compartment model in pigs (y = -0.05 + 1.01x, r = 0.99) and in
      humans (y = 0.57 + 0.88x, r = 0.93). Estimates of renal cortical blood flow by O
      15 water in human volunteers were also linearly correlated with those by N-13
      ammonia and the Patlak graphical analysis (y = 0.71 + 0.84x, r = 0.86). Renal
      cortical blood flow estimates were highly reproducible both with N-13 ammonia and
      O-15 water measurements in humans. It is concluded that the Patlak graphical
      analysis with N-13 ammonia dynamic positron emission tomograpic imaging renders
      accurate and reproducible estimates of renal cortical blood flow. Moreover, the
      graphical analysis approach is 1,000 times faster than the standard model fitting
      approach and suitable for generating parametric images of renal blood flow in the
      clinical setting.

PMID- 8264159
TI  - Polymerase chain reaction and focal contact formation indicate integrin
      expression in mesangial cells.
AB  - Cultured kidney glomerular mesangial cells (MCs) allow the role of extracellular
      matrix (ECM) and growth factors in glomerular inflammatory disease to be studied.
      To investigate the potential of MCs to interact with matrix components, the
      expression of integrin mRNA in cultured MCs was examined by polymerase chain
      reaction (PCR), by Northern blotting and by immunofluorescence. In addition, the
      effect of matrix substrates on mRNA expression was assessed by PCR. Northern
      blots with cDNA probes to integrin alpha-chains revealed that MCs expressed alpha
      1, alpha 3 and alpha 5 integrin mRNA. alpha 1 and alpha 3 were the major
      messages. No alpha 2, alpha 4 or alpha 6 were detectable. RT-PCR revealed that
      alpha 2 and alpha 6 were also expressed at low levels. The control cells, HT1080,
      expressed alpha 2, alpha 3, alpha 4, alpha 5 and alpha 6 mRNA, and Rugli
      expressed alpha 1, alpha 3 and alpha 5, supporting previous studies.
      Immunocytochemistry confirmed that alpha 1 beta 1, alpha 2 beta 1, and alpha 5
      beta 1 integrins were expressed and that they were concentrated into focal
      adhesions (alpha 1 beta 1 on type I collagen and laminin; alpha 2 beta 1 on type
      I collagen; alpha 3 beta 1 on type I collagen, laminin and fibronectin; alpha 5
      beta 1 on fibronectin). alpha 6 beta 1 was not detected in focal contacts.
      Attachment, spreading, and formation of talin and integrin containing focal
      contacts still occurred when endogenous protein synthesis was blocked with 30
      micrograms.ml-1 cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264160
TI  - [Nephroptosis in children].
AB  - The author suggests a modification of the Rivoir-Pytel-Lopatkin operation for
      children with II-III degree nephroptosis. It consists in careful atraumatic
      separation from the surrounding tissues of the whole kidney, the upper third of
      the ureter, and the main vessels of the kidney for a distance from its hilus to
      the site of their origin from the aorta and drainage into the inferior vena cava.
      A pedicle graft measuring 3-3.5 cm in width and thickness and 13-15 cm in length
      is formed from the psoas major muscle with maintained circulation. The graft is
      sutured to the lower pole of the kidney preserving the intactness of the capsule.
      Care is taken that the main vessels of the raised kidney are situated, where
      possible, perpendicular to the aorta and inferior vena cava. A band is worn for
      12-18 months after the operation. Eight children were operated on. The late-term
      results in follow-up periods of 6 months to 3 years are favorable.

PMID- 8264161
TI  - [Surgical correction of multiple ureter obstructions in children].
AB  - Obstruction in the pyeloureteral region is often combined with an obstacle of an
      anatomical or functional character in the distally located parts of the ureter.
      The authors treated by operation 80 patients with congenital hydronephrosis in
      the period from 1986 to 1991. An additional distally located stricture of the
      ureter was found during intraoperative catheterization in 10 cases. In 9 of 10
      cases the obstacle was at a distance of 1.7-2.0 cm from the pelvioureteral
      junction. Due to the small distance between the strictures the affected segment
      could be resected and an Andersen-Haynes anastomosis formed. The authors believe
      that the presence of double obstructions indicates marked dysplastic changes of
      the ureteral wall. In view of this, the use of optic magnification, microsurgical
      instruments, and ultrathin suturing material in the formation of the anastomosis
      is recommended. In 3 children operated on by the above discussed method the
      postoperative course was uneventful. A clinical case is given in illustration. It
      is suggested in the discussion that the indications for retrograde pyelography
      may be widened so as to identify additional strictures of the ureter at the
      diagnostic stage.

PMID- 8264162
TI  - [Predicting in the course of scoliosis-related disorders of vertebral
      segmentation in children].
AB  - The article deals with the analysis of the natural course of +seoliosogenous
      disorders of vertebral segmentation in 26 patients during the first three years
      of life. The authors determined the prognostic criteria of the rate of increase
      of the deformity (angle of scoliosis) during the first visit to the doctor and
      the asymmetry index according to which the course of the disease can be
      prognosticated with a high degree of probability during the patient's first visit
      to the doctor. If the patient had radiographs taken at an interval of 6-12 months
      an additional test was applied-the apical vertebra growth coefficient. The
      suggested prognostication criteria make it possible to avoid prolonged
      observation over the patient during which many radiologic studies are resorted
      to.

PMID- 8264163
TI  - [Pathogenesis of congenital aneurysm of the internal jugular veins].
AB  - Congenital aneurysm of the internal jugular veins is a developmental anomaly of
      the venous wall occurring as a consequence of hypoplasia of the smooth-muscle
      element of the media and deficiency of the elastic framework. The disease is
      marked by a progressive course linked with enlargement of the aneurysm and
      thinning of its walls. Hemoliquorodynamic disorders uncorrectable by drugs
      develop in childhood and are registered during rheoencephalography. In view of
      this the existence of an aneurysm is an indication for operative treatment for
      restoration of adequate drainage of venous blood from the head.

PMID- 8264164
TI  - [Subdiaphragmatic abscesses in children].
AB  - At the clinic of pediatric surgery of the Sverdlovsk Medical Institute 30
      children aged from 3 to 14 years were treated for subdiaphragmatic abscesses in
      1979-1989. In 27 of them the abscesses occurred in 6 days to 6 months after an
      emergency operation. The largest group (19 children) was formed of patients who
      underwent operation for destructive appendicitis and peritonitis. The
      subdiaphragmatic abscess was found on the left side in 16 (53.3%) and on the
      right side in 14 (46.6%) cases. In 11 (36.6%) patients in was combined with
      abscesses of other localization. X-ray and ultrasonic studies and, occasionally,
      computed tomography were used along with clinico-laboratory methods in
      establishing the diagnosis of subdiaphragmatic abscesses. Operations were
      performed on 29 patients. One patient was treated by puncture followed by
      drainage of the abscess after Seldinger. The choice of the approach was
      determined by the localization of the abscess. The intraperitoneal approach was
      used in 11 cases (36.6%), Klermon's extraperitoneal approach in 16 (53.3%),
      Melnikov's extrapleural approach in 2, and the posterior retropleural approach in
      one case. Complex intensive therapy was applied in the postoperative period.
      Among the 30 patients one died from sepsis and developed polyorganic
      insufficiency.

PMID- 8264165
TI  - [Differential diagnosis of diseases (the role of "volatile processes")].

PMID- 8264167
TI  - [Treatment of generalized purulent appendicular peritonitis in children].
AB  - Experience in the treatment of 137 children with a most severe and complicated
      course of generalized purulent peritonitis of appendicular genesis is
      generalized. It is shown that such patients must be concentrated in centers of
      pediatric surgery providing the possibility of applying a complex of diagnostic
      examinations and therapeutic measures, including purposeful antibiotic therapy,
      differentiated immunocorrection, and effective detoxification. The detoxification
      and immunocorrection effect of discrete plasmapheresis with two-stage "washing
      out" of the red cells is illustrated in the discussion of 22 cases. It is pointed
      out that in operations for generalized purulent peritonitis the abdominal cavity
      must not only be cleansed but also drained adequately and intubation of the
      intestine must be carried out with aspiration of its content for 3-5 days and
      application of enterosorption through an intestinal tube. A complex of
      organizational and therapeutic measures made it possible to reduce considerably
      the mortality rate in acute appendicitis and its complications in the Moscow
      Region.

PMID- 8264166
TI  - [Evaluation of methods for local treatment of generalized purulent peritonitis of
      appendicular origin in children].
AB  - The work is based on the analysis of treatment of 212 children with generalized
      purulent peritonitis of appendicular origin at 7 different pediatric surgical
      clinics of Russia. The total mortality rate was 1.9%. It is shown that the
      removal of pus from the abdominal cavity by aspiration has no advantages over its
      removal by means of moistened tampons. Irrigation of the abdominal cavity during
      the operation does not affect essentially the results of treatment of patients
      with generalized purulent peritonitis. Drainage of the abdominal cavity by means
      of an aspiration drain installed properly and methodically leads to a lesser
      number of postoperative abdominal abscesses and continuing peritonitis.
      Administration of antibiotics into the abdominal cavity at the end of the
      operation and in the postoperative period does not influence significantly a
      decrease in the incidence of postoperative purulent complications. Peridural
      anesthesia has no advantages over other methods in the control of intestinal
      paresis and prevention of adhesive intestinal obstruction.

PMID- 8264168
TI  - [Extracorporal and endogenous detoxication in appendicular peritonitis in
      children].
AB  - The article deals with the method for detoxification of patients with diffuse and
      generalized peritonitis. Exogenous detoxification was accomplished by the open
      method for peritonitis management (laparotomy), endogenous detoxification was
      achieved by well-founded intraperitoneal and intravenous administration of
      proteolysis inhibitors. Comparison of the two groups of patients who were
      operated on showed marked reduction of mortality from 22.2% to 2.7% in
      generalized peritonitis and from 9.6% to zero in diffuse peritonitis.

PMID- 8264169
TI  - [Methods of surgical treatment of Hirschsprung's disease in newborns].
AB  - Fifty-nine newborn infants with Hirschsprung's disease were treated at the Saint
      Petersburg Center of Surgery of Developmental Anomalies from 1978 to 1991. The
      typical rectosigmoid form was found in 47.5% and a long zone of agangliosis in
      35.6% of children. Mortality rate--16.7%. According to the development of
      enterocolitis, three variants of the course of the disease in the newborns were
      distinguished. It is shown that the informativeness of the diagnostic methods
      increases with the growth of the infants, and the final diagnosis of
      Hirschsprung's disease is best established at the age of over two weeks on the
      basis of repeated or initially postponed contrast study of the large intestine.
      Inefficacy of nonoperative treatment conducted for 2-3 days and recurrence of
      symptoms of intestinal obstruction are indications for operative decompression of
      the intestine. The performance of one-stage radical operation at the age of about
      one month is advisable in an uncomplicated course of the disease.

PMID- 8264170
TI  - [Anoplasty for anorectal anomalies in children].
AB  - The work analyses the causes of insufficient air-tightness of the anal canal in
      the postoperative period (in children operated on for anorectal developmental
      anomalies), which leads to anal incontinence. The authors suggest a method for
      anoplasty based on: (1) performance of sphincteroplasty with consideration for
      the function of three muscles forming the external sphincter of the anal canal;
      (2) formation from the musculo-serous coat of the intestine subjected to the pull
      through procedure a soft elastic pad lining the canal on the inside; (3) creating
      conditions for adherence of the mucous coat of the intestine to the walls of the
      neoanal canal. Manometric, CT, and ultrasonic special methods of examination
      showed that with the use of the suggested method the obturative pressure in the
      neoanal canal increases, "prolapse" of the mucosa of the operated on intestine is
      prevented, the accumulative and evacuative functions of the rectum are improved.
      The causes and errors which led to poor results (2 cases) are analysed. In the
      remaining 42 cases the results were good and satisfactory.

PMID- 8264171
TI  - [Congenital stenosis of the anus and rectum (Problems of nosology and
      pathogenesis)].
AB  - The work deals with the differential analysis of two forms of congenital rectal
      stenosis--"membranous" which is consequent upon incomplete obliteration of the
      anal membrane and "tubular" with involvement of the rectum along its length. It
      is pointed out that in most cases tubular rectal stenosis is a component of the
      complex of anomalies of the caudal region described for the first time by G.
      Currarino (1981) and called the ASP-triad. From analysis of 12 cases of the ASP
      syndrome a new scheme of the pathogenesis of the complex of anomalies
      constituting the syndrome is suggested. The authors identified a component of the
      syndrome which was not described earlier, namely, specific dysplasia of the
      pelvic floor and the external sphincter muscles of the anus, which provided the
      basis for naming the complex the PFASP syndrome (PF--Pelvic Floor Dysplasia).
      Problems of surgical correction of the PFASP complex of anomalies are discussed.
      A pathogenetically substantiated analysis of postoperative complications is made.

PMID- 8264172
TI  - [Nonparasitic cysts of the spleen in children].
AB  - The article generalizes the experience in the diagnosis and treatment of
      nonparasitic cysts of the spleen in 8 children aged from 7 to 14 years. The
      causes of the first visit to the doctor are discussed in detail and the clinical
      manifestations of this pathological conditions are analysed profoundly. The
      various methods of examination used in the diagnosis of this disease are
      evaluated. Seven patients were subjected to operative treatment--splenectomy. In
      one case a small cyst was recognised by ultrasonic examination, the child is kept
      under observation. As the result of histological study false (posttraumatic)
      cysts were diagnosed in 5 and true (epidermoid) cysts in 2 cases. Significant
      morphological changes in the residual tissue of the removed spleens brings to
      minimum the possibility of applying autotransplantation methods in splenectomy.

PMID- 8264173
TI  - [Treatment of hematogenic osteomyelitis in newborns].
AB  - The authors studied the immunobiological condition of the newborn's organism and
      the process of bone structure reparation before and after direct immune
      hemotransfusions and transplantation of bone marrow with the stroma in a mixture
      with antibiotics into the focus of osteomyelitis in the bone of newborn infants
      with consideration for the clinical manifestations of the disease, the stage of
      osteomyelitis, and the efficacy of the applied treatment. The authors examined
      215 newborns with acute hematogenous osteomyelitis. The predominant site of
      localization of acute hematogenous osteomyelitis in the newborn infants were the
      epimetaphyseal (54.5%) and metaphyseal (39.6%) parts of the long tubular bones.
      The donors were immediate relatives compatible according to the ABO system and
      the rhesus factor, who underwent complete examination for HIV infection, the
      Australia antigen, and the Wasserman reaction, and who were immunized
      preliminarily with the staphylococcus anatoxin. The authors note the favorable
      immediate and late-term results of treatment which were confirmed by radiological
      restoration of the bone structure. The immunological values testify to increase
      of cellular and humoral immunity. Study of the late-term results of treatment
      confirm the decrease of the number of orthopedic complications.

PMID- 8264174
TI  - [Treatment of pathologic hip dislocation caused by hematogenic osteomyelitis in
      children and adolescents].
AB  - The article discusses 94 patients with pathological dislocation of the hip after
      hematogenous osteomyelitis who underwent reconstructive-restorative operations on
      101 joints. According to the clinical and X-ray signs, all patients were divided
      into 4 main groups. The types of surgical interventions performed depending on
      the severity of involvement of the proximal part of the femur and the acetabulum
      are indicated. Patients with acute hematogenous osteomyelitis of the proximal
      femur must be subjected to early orthopedic prophylaxis and kept under strict
      medical control of a specialist. Pathological dislocations of the hip are managed
      by operation which is determined by the type of the condition.

PMID- 8264175
TI  - [Postoperative peritonitis in children].
AB  - The peculiarities of the manifestation of progressive and postoperative
      peritonitis under conditions of intensive postoperative therapy are shown on
      basis of generalized experience in the treatment of 48 children who underwent
      early relaparotomy for postoperative complications. The following causes of
      purulent peritonitis were determined during relaparotomy: progressive peritonitis
      in 14, postoperative peritonitis in 30, incompetence of the intestinal sutures in
      9, and perforating ulcers of the small intestine in 3 patients. Manifestations of
      postoperative peritonitis in 13 patients (group I) treated in the intensive care
      department after operation for peritonitis of appendicular origin in whom the
      early postoperative period was uneventful were compared with those in 12 patients
      (group II) who were in the intensive care department after the first operation
      and who were later subjected to early relaparotomy. Besides the well-known
      manifestations of purulent peritonitis complicating an operation on the abdominal
      organs, other objective signs characterizing the peculiarities of intensive
      therapy were revealed. Among them are increased volume of the stagnant gastric
      contents and increased volume and doses of corrective therapy for the control of
      dehydration and hypokalemia. To correct dehydration and loss of potassium during
      intensive therapy, much more solutions and potassium must be administered than in
      children with an uneventful postoperative course.

PMID- 8264176
TI  - [Attachment to electric suction pump for automatic regulation of vacuum intensity
      in the treatment of pleural complications in children].
AB  - The authors report on the use of an attachment for automatic regulation of vacuum
      intensity on a surgical electric sucking pump applied in the treatment of
      pneumothorax, pyopneumothorax, and pyothorax in children. The suggested
      attachment causes periodic removal of the exudate and air from the pleural cavity
      by automatic switching on of the pump and creates favorable conditions for
      cleansing of the cavity. The attachment of the electric sucking pump is cheap,
      easy in exploitation, simple in assemblage, and may be used for cleaning the
      pleural cavity with high precision of the necessary degree of exhaustion.

PMID- 8264177
TI  - [Equinus valgus deformity of the foot in children with infantile cerebral
      paralysis and its surgical correction].
AB  - The authors explain the mechanism of pes equino-planus-valgus formation in
      patients with infantile cerebral paralysis (ICP) and describe in detail the
      clinico-radiological characteristics of such patients. The authors possess
      experience in the treatment of 31 patients who were operated on by a method
      suggested by A. M. Zhuravlev--osteomyoplasty of the root of the foot. The method
      removes all the components of the deformity and creates conditions preventing its
      recurrence. Study of the late-term results in postoperative follow-up periods of
      6 months to 2 years shows the method to be much less injurious and more effective
      than the other methods of treatment and allow it to be recommended for
      application in specialized medical establishments for patients with ICP.

PMID- 8264178
TI  - [Cicatrix phimosis and problems of circumcision in young children].
AB  - The article deals with the author's modified operation for circular excision of
      the prepuce with adaptation of the wound edges without sutures. The operation was
      performed on 200 patients under local infiltration anesthesia in the last four
      years. The advantages of the modified operative method are shown, schemes of the
      pathogenesis of cicatricial phimosis and its complications are compiled, a
      comparative evaluation of the existing types of operations for circular excision
      of the prepuce is made and their shortcomings are shown. The variant of the
      operation is suggested for introduction into pediatric surgery.

PMID- 8264179
TI  - [Kidney autotransplantation in ureter injuries and diseases children].
AB  - Six operations for kidney autotransplantation into the ipsilateral iliac fossa
      were conducted on children aged from 2 to 14 years. In 2 children the operation
      was performed for a posttraumatic defect in the ureter of a considerable length.
      Severe neuromuscular dysplasia of the ureter in maintained function of the kidney
      was the indication for operating on 4 children. No complications occurred in 5
      operations. One transplanted kidney had to be removed because of renal artery
      thrombosis resulting from damage inflicted to the endothelium during washing of
      the kidney. Operation for autotransplantation of the kidney is a permissible
      alternative of the traditional methods of replacement or plastics in long
      posttraumatic strictures and congenital developmental anomalies of the ureter.

PMID- 8264180
TI  - [Surgical treatment of necrotizing enterocolitis in newborns (Review of foreign
      literature)].

PMID- 8264181
TI  - [Gastric torsion in a child].

PMID- 8264182
TI  - [Rare form of cloacal atresia of the rectum].

PMID- 8264183
TI  - [Rare localizations of echinococcosis].
AB  - The author describes 28 observations of rare localizations of the echinococcosis
      in patients with proved "omission" of the hexacantic embryo of the liver and the
      lung barrier. It has been established that the spleen is most often affected. The
      necessity of diagnostication with modern visual technics--echography and KT--has
      been proved, as well as confirmation of the specificity of the process with the
      immunological reactions for echinococcosis. The approach for an organ-preserving
      operation at the spleen localization has been emphasized, stating as well the
      indications for splenectomy. General theoretical and practical conclusions for
      the diagnostics and the treatment of these localizations have been made.

PMID- 8264184
TI  - [Transduodenal papillosphincteroplasty in the treatment of choledocholithiasis
      and benign stenosis of the terminal choledochus and papilla Vateri].
AB  - The article contains data form the surgical treatment of 297 patients with
      choledocholithiasis and benign stenosis of choledochus terminal and papilla
      Vateri, treated in the Academy of Medicine-General and Operative Surgery within
      the period 1983-1992. The data relate to 59 patients with biliodigestive
      anastomosis, 114 patients with choledochotomy and T-drainage (Kehr drainage) and
      124 patients with transduodenal papillosphincteroplastica. The postoperative
      lethality in the general series of patients was 3.03%, for the patients with
      transduodenal papillosphincteroplastica--0.8%. The serious complications in the
      postoperative period in the cases of papillosphincteroplastica represent 0%,
      while the excellent and very good results in the distant period--95.16%. The
      authors state the precise moments of the surgical techniques in the cases of
      transduodenal papillosphincteroplastica and their importance for the
      postoperative results. The authors specify the indications and the
      contraindications for carrying out the different surgical and endoscopic
      procedures.

PMID- 8264185
TI  - [Our experience in the diagnosis and treatment of traumatic pneumothorax].
AB  - The clinical material summarized is derived from the observation of 150 patients.
      The accent is put on the faults in the X-ray interpretation of the pneumothorax
      and on the mistaken tactics in the treatment of the pneumothorax, which led to
      four lethal cases. The attention is drawn to the importance of the prompt
      physical study of traumatic patients, which gives the opportunity for prompt
      diagnosis and urgent adequate treatment. The indications have been precised
      relating pleurocentesis, pleural drain and when lacking aerostasis for
      thoracotomy.

PMID- 8264186
TI  - [The problems of severe combined chest and heart trauma].
AB  - On the basis of the experience and the analysis of 3818 cases of combined chest
      traumas the injuries in different anatomical areas have been observed. A special
      place was given for the diagnostics, the variety of the clinical conditions, the
      treatment and the prognosis of the reasons for lethality in cases with such
      traumas. With the increase of the affected anatomical areas the lethality
      increases proportionally too. At double, triple, fourfold, fivefold and sixfold
      combinations we have respectively 6.35 to 100% lethality. The indications for
      early surgical treatment have been stated. The acute respiratory failure
      (decompensation) and the shock in the combined traumas have been discusses as
      well.

PMID- 8264187
TI  - [Changes in the water-electrolyte and protein balance of the body in acute
      gastrointestinal ulcerative hemorrhage].
AB  - The authors studied 127 patients, divided into 4 groups, relating to the
      haemorrhage stage in accordance with the classification of Lutsevich. It has been
      established that there exist changes in the hydroelectrolytic and protein balance
      of the patients having acute gastrointestinal ulcerative haemorrhage.

PMID- 8264188
TI  - [Ataralgesia with nalbuphine-midazolam instead of fentanyl-midazolam analgesia.
      Anesthesia and the postoperative control of pain. A preliminary report].
AB  - Nalbuphine-midazolam ataractanalgesia has been studied in anaesthesia and
      postoperative analgesia. Attention has been applied to the efficiency,
      pharmacological activity, side effects, adverse reactions of nalbuphine as a
      fentanyl substitute. Preliminary results show that nalbuphine could be used
      safely as anaesthesia component and as postoperative analgetic.

PMID- 8264189
TI  - [Urethrovesicopexy by the Marshall-Marchetti-Krantz method with urodynamic
      control in women with stress urinary incontinence].
AB  - For the period 1987-1991 the authors have been diagnosticated and operated in the
      Clinic for General Urology 21 women with stress incontinentio of the urine. The
      medium age of the patients was 47 years. With all of the patients detailed
      anamnesis have been made, whereas for determining the diagnosis X-ray and
      urodynamic methods had been used. According to the classification of Ingelmann
      Sundberg 17 women had stress incontinentio in the second stage, and 4 women--in
      3rd stage. The patients were operated suprapubically by the original method of
      Marshall-Marchetti-Krantz. For the assessment of some postoperative results the
      authors used t-criteria and P-indication.

PMID- 8264190
TI  - [Methodological recommendations for the study and management of patients with
      abdominal aortic aneurysms].
AB  - The life of the patients having aneurysms of aorta abdominal is in danger
      seriously because of the strong tendency of the aneurysms to make ruptures with
      the expansion of the diameter. The inhibition, even the retardation of the
      expansion of the aneurysms is impossible and the treatment can be only a surgical
      one. Stating the diagnosis aneurysm of aorta abdominal in the not specialized
      hospitals appears possible only in 30-50% from the cases. The frequency of the
      faults with the symptomatic aneurysms is comparatively high and 50% of the
      patients are being set for operations with a diagnosis "acuta abdomen". In the
      cases of ruptures the number of the faults reaches up to 72%. The lethality of
      the planned operative treatment is 3-5%. The lethality in the cases of urgent
      operation with ruptures is 50-75%. In order to avoid the faults and the
      complications in diagnosis of the illness we have made practical recommendations
      for consideration and discussion of the diagnosis and the tactics with patients
      having abdominal aneurysms. They are recommended for use in dispensary, surgical,
      urological and cardiological consulting rooms and the respective departments of
      the hospitals without special profile.

PMID- 8264191
TI  - [Methods for the experimental study of the area around a traumatic skin wound].
AB  - The author describes the methods for experimental study of the area around a
      traumatic skin wound, which up to now have been neglected by the hospital doctors
      and the investigators. The choice of the experimental animals and the methods for
      the preliminary preparatory work with them have been described. The author in
      details specifies the ways of injuring the skin--by thermal burn, mechanical
      crushing and combination of both, chemical injury and incision wound. All the
      manipulations of wounds are treated in inhalation ether anaesthesia. The methods
      proposed ensures replications and makes the results precise and sure. This fact
      gives the opportunity for usage of the methods for assessment and analysis of
      medicinal preparations and other means for treatment of wounds. The methods was
      created and used in experiments with 1200 experimental animals.

PMID- 8264192
TI  - [Methods for the functional assessment of the degree of recovery in the victims
      of burns].
AB  - The objectification of the functional recovery of the patients having burns in
      very important for the correct determination of their working capacity. The
      general surgical criteria for the functional assessment can be applied mostly in
      defining the degree of the recovery of the motor functions, but do not reflect
      the specific evolution of the recovery of the epithelial tissue of the skin and
      the skin implantation after burns. The recovery of the patients having burns can
      be considered into two separate, but closely related aspects: 1. Functional
      recovery of the motor apparatus, where we can apply the following antropo- and
      physiometrical methods: angelometry, manual dynanometry, statical support
      capability of one lower limb and plantography. 2. Functional recovery of the
      restituted skin cover, where we observe the following clinical characteristics:
      colour, elasticability and moving ability of the skin cover, secondary injury,
      sensitivity of the restituted skin, necessity of observing medical safety regime.
      The usage of objective criteria for assessment of the degree of functional
      recovery of the injured skin supplements the methods for assessment of the
      recovery of the support-motor apparatus and reflects the specificity of the burn
      trauma. The usage of the said methods and the complex assessment therefrom will
      help the experts doctors to estimate right the degree of the lost work-capability
      and thus for making an objective assessment of the insurance.

PMID- 8264193
TI  - [An experimental study of chemical necrectomy in chemical injuries of the skin].
AB  - The authors studied experimentally the morphological changes of injuries and the
      surrounding areas after a skin chemical injury caused by sodium hydroxide,
      sulphuric acid and chlorhydric acid under the influence of acidic necrolytics-
      40% benzoic acid and 40% salycilic acid in unguentus. The necrolytics are applied
      on the injured areas immediately upon getting the wound or on the 4th day
      thereafter, while the morphological study is carried out after getting off the
      necrosis. It has been established that the necrolysis in the case of sodium
      hydroxide was not effected by the 28th day. The processes in the tissues upon
      acidic injuries do not differ from the spontaneous healing process.

PMID- 8264194
TI  - [Aggressive muscular-aponeurotic fibromatosis. Its clinical picture and
      morphological study].
AB  - The authors report 24 cases with aggressive muscle-aponeurotic fibromatosis for
      the period 1985-1990. Eleven cases with proved fibrosarcoma have been studied as
      well. From the total 35 cases the authors have observed 5 cases with localization
      on the front abdominal wall in women, and the remaining cases are as follows: 9
      patients with thoracic girdle (c. membri superioris); 9 patients--in the head
      area; 5--in the chest area; 12--in the limbs; 2--in the lumbar area.

PMID- 8264195
TI  - [The early selection of patients with a hemorrhage from gastric and duodenal
      ulcers].
AB  - For the period 1985-1991 446 patients with haemorrhage of gastric ulcer (95) and
      with haemorrhage of duodenal ulcer (351) have been studied, among them 314 men
      and 132 women. While staying at the hospital the patients were subjected to
      comparison for the surgical activity and the lethality, which lead us to the
      risky contingent. The symptoms of the illness were divided into groups according
      to the syndromes leading to nosological entity. Comparing each one of the
      clinical indications and syndromes of the lethality and the surgical activity, we
      have formed prognostical and risky factors, and according to them we have
      classified the patients into risky groups. This method of approach differentiated
      the stages of the early selection of patients with haemorrhage of gastroduodenal
      ulcer and made in methods by which we want to state the prognosis of the illness
      and to improve it, thus decreasing the lethality.

PMID- 8264196
TI  - [The modern differential diagnostic possibilities in chordoma].
AB  - The authors report five cases with chordoma. The diagnosis has been determined
      histologically on the basis of the operative material. The chordomas have a slow
      growth and a tendency to infiltrate the adjacent tissues and organs. That makes
      their surgical treatment difficult. A characterizing feature for them is the
      tendency to make recidivations and the difficulty in setting the differential
      diagnosis in metastasis of light-cell carcinomas.

PMID- 8264197
TI  - [A case of a choledochocele in a 14-year-old girl].

PMID- 8264198
TI  - [A case of dislocation of the spleen appearing as "acute surgical abdomen"].

PMID- 8264199
TI  - [A case of lymphoma (non-Hodgkin's type) of the stomach].

PMID- 8264200
TI  - [A case of multiple progressive hamartoma of the liver].

PMID- 8264201
TI  - [Echinococcosis in the gluteal region].

PMID- 8264202
TI  - [Branchioma of the tracheal bifurcation--a case report].

PMID- 8264203
TI  - [A radiation burn with a total defect of the abdominal wall].

PMID- 8264204
TI  - [Spontaneous recovery in perforated gastroduodenal ulcer. The indications for
      conservative treatment].
AB  - Two observations of patients, having perforated duodenal ulcer, not operated,
      where spontaneous recovery was achieved, have been reported. The said opportunity
      has been interpreted in connection with the accepted method for conservative
      treatment of gastroduodenal ulcer. The indications and the contraindications for
      the conservative treatment have been stated.

PMID- 8264205
TI  - [What is new in neuro-ophthalmology? Diagnosis, therapy and patient education in
      optic nerve neuritis].
AB  - The diagnosis of optic neuritis is based on clinical signs and symptoms.
      Ancillary testing is of little medical value, but helpful to evaluate the risk of
      developing multiple sclerosis and for proper counseling of the patient. The
      visual field defects caused by optic neuritis are less often central, but most
      often altitudinal or sectorial, and thus of little help to differentiate between
      papillitis and anterior ischemic optic neuropathy. In contrast to common belief,
      the usual therapy with oral prednisone at an initial dose of 100 mg/day may be
      harmful. This therapy does not accelerate recovery of visual function and does
      not lead to a better final result but increases the risk of new episodes of
      neuritis and may favour the development of multiple sclerosis. In the case of
      severe visual loss (visual acuity < or = 0.1) a megadose-therapy with 1000 mg
      methylprednisolone/day accelerates the recovery of visual function. Side effects
      of the megadose therapy are infrequent and not severe. In the case of moderate
      visual loss (visual acuity > or = 0.5) no therapy is advocated.

PMID- 8264206
TI  - [Keratoplasty in childhood. Report of 71 keratoplasties].
AB  - BACKGROUND: Keratoplasty is a routine method in adults but there are some
      additional problems in children. These include difficulties in examining the
      patients, amblyopia and an increased rate of graft rejection. PATIENTS AND
      METHODS: Between 1980 and 1990 71 keratoplasties in 66 eyes of 61 patients under
      16 years of age were performed. The indications and results were studied
      retrospectively and since 1987 prospectively. The average follow-up was 24
      months. Main indications were traumatic scarring (22 eyes), corneal dystrophy (13
      eyes), scarring after keratitis (10 eyes), graft failure (7 eyes), and chemical
      burn (5 eyes). There were 15 lamellar homologous not HLA-matched keratoplasties,
      11 autologous penetrating rotating, 42 penetrating homologous not HLA-matched,
      and 3 penetrating homologous HLA matched. The most frequent complications were
      loosening or rupture of the suture in 38% and graft rejection in 20% of the
      homologous penetrating keratoplasties. 10 of 15 eyes after lamellar grafting
      showed a clear graft at the last control. 40 of 42 eyes after penetrating
      keratoplasty had also a clear graft, however second keratoplasties were necessary
      in 4 eyes. 21 of the 42 eyes after penetrating keratoplasty developed a visual
      acuity of 0.5 or better. CONCLUSION: We recommend interrupted single sutures for
      keratoplasties in children and an earlier suture removal to avoid severe suture
      problems. Visual outcome depends on the primary diagnosis and on avoiding
      irreversible amblyopia. In cases of traumatic corneal and lens opacification an
      early rehabilitation of the optic system is important, therefore in patients
      under 7 years of age we prefer a posterior chamber lens implantation for a more
      effective amblyopia therapy.

PMID- 8264207
TI  - [Synthetic skin replacement for temporary wound coverage in eyelid surgery].
AB  - BACKGROUND: Large uncovered defects of lid-skin which extend beyond the margin of
      the orbital rim frequently cause wound contracture and malposition of the lid.
      PATIENTS AND METHODS: Between April 1989 and October 1992 we have successfully
      used synthetic skin in severe cases of traumatic skin ablation (n = 3) and in
      complicated tumor surgery of the lids and of the medial canthal area (n = 14).
      Polyurethan foam material was used for temporary skin replacement (Epigard).
      RESULTS: The synthetic skin stimulated wound granulation and vascularization of
      the host area before final closure of the defect was achieved. No wound
      contracture occurred. CONCLUSION: Temporary bandage with synthetic skin is
      recommended if large skin defects can not be closed within 48 hours.

PMID- 8264208
TI  - [Results of laser coagulation of retinal branch vein occlusions].
AB  - BACKGROUND: The benefit of laser treatment in patients with branch retinal vein
      occlusion (BRVO) is established in the literature. We investigated the
      relationship of morphological and fluorescein angiographic findings with the
      results of laser treatment. PATIENTS AND METHODS: Of 211 examined patients with
      BRVO argon-laser coagulation was performed in 121 (57%). Laser treatment was done
      in all patients with preretinal neovascularization and in patients with macular
      edema 3 months or more after the onset of occlusion with visual acuity < or =
      20/40. Follow up examinations were performed in 3 months intervals with the last
      examination 11.7 months on average after treatment. Statistical analysis was done
      by Wilcoxon-test. RESULTS: Mean visual acuity before laser coagulation was 20/60,
      after laser treatment 20/50. Visual acuity in all patients improved significantly
      after laser treatment (p = 0.0001). A significant improvement occurred when
      treatment was performed within 3 to 4 months after onset (p < 0.0001), in
      patients with macular edema in the ischemic (p = 0.0005) and non ischemic type (p
      = 0.036), in patients without preretinal neovascularization (p < 0.0001) and
      without vitreous hemorrhage (p = 0.0001), in patients between 51 and 60 years (p
      = 0.0001) and between 41 and 50 years of age (p = 0.0086), in vein occlusions
      with intraretinal hemorrhages ++ (p = 0.0001), with hard exsudates + (p = 0.0047)
      in vein occlusions of the temporal superior (p = 0.0016) and the temporal
      inferior branch (p = 0.028) and in patients with diffuse dye leakage + (p =
      0.0036) and ++ (p = 0.007). No significant visual improvement was found in
      patients with ischemic maculopathy, hard exsudates ++, preretinal
      neovascularization and vitreous hemorrhage, diffuse intraretinal dye leakage ,
      dye leakage ++ and from retinal vessels and in patients < or = 40 and > 60 years
      of age. CONCLUSIONS: Laser treatment in BRVO according to the criteria of the
      study is beneficial and results in significant visual improvement.

PMID- 8264209
TI  - [The Array multifocal lens--functional principle and clinical results].
AB  - BACKGROUND: Common refractive bifocal IOLs feature 2 or 3 spherical zones with
      different refraction; the design of the Array multifocal IOL consists of 5
      concentric zones, each of them providing a progressive near addition with
      multiple foci by means of an aspherical surface. METHODS: As a part of a
      prospective study, distance and near visual acuity, contrast sensitivity, glare
      and depth of field were examined in 15 patients with the Array lens and a
      monofocal control group 12 months after implantation. Subjective assessment of
      the optical quality was performed by detailed asking for optical symptoms.
      Results were retrospectively compared with the one year follow-up of 15 patients
      with diffractive bifocal IOLs. RESULTS: No difference was found for best
      corrected far and near visual acuity and sensitivity for high contrasts. Glare
      and sensitivity for low contrasts of the monofocal IOL was significantly superior
      to both multifocal models. Array IOL and diffractive IOL achieved a near acuity
      of Nieden 2-1 with only distance correction; defocus curves revealed an increase
      in the depth of field, but with a superiority of the Array lens in intermediate
      imaging. Optical symptoms as halos were much more frequent in patients with the
      diffractive IOL than in the Array group. CONCLUSIONS: Functional results of the
      Array multifocal IOL seem to be comparable to those of the diffractive bifocal
      IOL, but with the advantage of an improved intermediate imaging and a reduction
      of optical side effects.

PMID- 8264210
TI  - [Eye injuries in squash].
AB  - BACKGROUND: Since 1968, when the first commercial squash center has opened in
      Hamburg, squash has become very popular in Germany. Squash is played between two
      players in a closed court using racquets and a hollow rubber ball which could
      reach a maximum speed up to 225 km/h. According observations of English and
      American ophthalmologists there is an increased risk to get an eye injury in this
      game. Because of the isolation by the former existing wall, Berlin-West was an
      ideal place to study the ocular hazards of playing squash. METHODS: In 1991 about
      40,000 squash players existed in Berlin-West playing on 118 courts of 13
      commercial squash centers. During January to October 1991 case records of all
      hospitals with an emergency eye ambulance and of the eye residents were
      investigated, furthermore all patient records of 1989 and 1990 of the eye clinic
      of the university hospital Rudolf Virchow, department Charlottenburg, were
      examined retrospectively. RESULTS: All over 234 sports-related eye injuries were
      registrated, 78 (33.3%) patients sustained the injury during a squash game, 43
      (18.4%) during soccer and 34 (14.5%) during playing tennis. 71 squash players
      were treated in an hospital ambulance, of these 15 required admission. A total of
      206 injuries were sustained by the players. The majority of injuries were
      superficial, but in 12 cases occured an hyphaema and in 13 an angle recession. In
      all admitted patients visual recovery was good, during the clinical follow up
      there were no perimetric, ophthalmoscopic or tonometric impairments. The initial
      loss of visual acuity of the injured eye compared to the other side was on the
      average 4.5 lines, at dismissal from the hospital it was on the average 2 lines.
      CONCLUSION: Because of the increased risk to get an eye injury during a game of
      squash, players should be encouraged to wear proper eye protection i.e. closed
      eye guards according to standards of North-American testing organisations.

PMID- 8264211
TI  - [Determination of retinal nerve fiber density in vivo using laser polarimetry].
AB  - BACKGROUND: A direct in vivo measurement of the retinal nerve fiber layer
      thickness enables new possibilities for the detection of nerve fiber defects.
      Using the principle of polarimetry the Nerve Fiber Analyzer has been told to
      measure directly the nerve fiber layer thickness in vivo. PATIENTS AND METHODS:
      We measured the nerve fiber layer thickness along a peripapillary circle and
      investigated the reproducibility in 10 independent measurements of 10 left eyes
      of ten normals. RESULTS: The nerve fiber layer thickness measurements varied
      between 10 and 130 microns for single pixel measurements. The coefficient of
      variation was 11.9 +/- 2.6 percent for a peripapillary circle while the temporal,
      nasal, superior and inferior quandrants were 19.2 +/- 3.6%, 19.5 +/- 4.7, 14.3 +/
      5.6 and 16.4 +/- 5.5 percent, respectively. Mean coefficient of variation in 10
      time evaluation of 5 single examinations of 5 different eyes was 1.8 +/- 1.1%.
      CONCLUSIONS: The first investigations demonstrate a good reproducibility of the
      measurements observed by the Nerve Fiber Analyzer. Supplementary to three
      dimensional optic disc topography and perimetry, nerve fiber layer thickness
      assessment may become an additional tool for diagnosis and follow-up of early
      glaucoma. The option of measuring along circle segments or areas instead a
      peripapillary circle consisting of a single pixel would increase the clinical
      value and reproducibility. Further studies are warranted to evaluate the accuracy
      of this new method of polarimetry.

PMID- 8264212
TI  - [Growth inhibition of intraocular proliferative explants under in vitro
      conditions by verapamil].
AB  - BACKGROUND: For the treatment of non neoplastic proliferations in the fundus, a
      nontoxic, proliferation-inhibiting long-term therapy would be desirable in
      addition to vitreoretinal surgery. In theory, the use of calcium channel blockers
      as a means of prevention appears promising. METHODS: In order to test the action
      of Verapamil in the above application, 42 preretinal, epiretinal and subretinal
      membranes were removed during pars plana vitrectomy between May, 1991 and June,
      1992. Following crushing, these were cultured under cell culture conditions.
      RESULTS: Cell division outside the membranes was seen in 27 cases. In 13 cases
      the minimum cell count was approximately 1000 per primary culture. Subcultures
      were prepared from each of the latter, the cells having been divided into four
      portions. Two of the samples were diluted with Verapamil in a concentration of
      0.25 microgram/ml. When cell fusion began, the number of intact cells in each
      sample was determined. Verapamil inhibited growth significantly (significance
      level of 0.93, P < 0.01). CONCLUSIONS: A larger number of cases would have to be
      studied to permit more comprehensive conclusions.

PMID- 8264213
TI  - [Fundus-controlled microperimetry with the scanning laser ophthalmoscope in
      macular diseases].
AB  - BACKGROUND: Scanning laser microperimetry allows focal sensitivity testing of any
      localization of the retina under direct visual control. Physiological or
      involuntary fixation shifts can be corrected by manual fundus-tracking. METHODS:
      For static fundus-controlled microperimetry we used a confocal scanning laser
      ophthalmoscope equipped with a helium-neon laser as light source for background
      illumination and for generating the stimuli by acousto-optic modulation. Fundus
      imaging was achieved by an infrared diode laser scanning synchronous with the
      helium-neon laser. In comparison computerized static projection perimetry was
      performed using the Humphrey Field Analyser, program 10-2. RESULTS: On the basis
      of four exemplary cases (macular hole, juxtafoveal pigment epithelium atrophy,
      subretinal neovascularization secondary to age-related macular degeneration) it
      is shown that extension and depth of scotomas can be recorded more precisely with
      scanning laser microperimetry than with conventional projection perimetry.
      Microscotomas can be detected. By using infrared laser for fundus imaging
      choroidal structures such as subretinal neovascular membranes can be visualized,
      even when moderate intra- or subretinal hemorrhages secondary to age-related
      macular degeneration are present. Thus focal sensitivity testing of the retina
      overlying neovascular membranes is possible. Simultaneous registration of
      fixation allows precise localization of the fixation point and its relationship
      to neovascular membranes. CONCLUSION: The advantage of fundus-controlled
      microperimetry is a precise examination of the impact of morphological changes on
      psychophysical functions of the macula. Due to its simultaneous registration of
      fixation fundus-oriented microperimetry is a very informative aid in the
      indication of laser therapy and the selection of different laser procedures in
      the treatment of subretinal neovascularizations.

PMID- 8264214
TI  - [Combined hamartoma of the retina and retinal pigment epithelium. CLinical
      Aspects and differential diagnosis to other melanocytic processes of the fundus].
AB  - BACKGROUND: The combined hamartoma of the retina and the retinal pigment
      epithelium is a rare but important differential diagnosis of the melanocytic
      lesions of the fundus. PATIENTS AND METHODS: We present a patient with the
      typical clinical picture and characteristic fluorescein angiography findings. The
      case report is followed by the discussion of the differential diagnoses and their
      specific signs. RESULTS: The combined hamartoma of the retina and the retinal
      pigment epithelium is a congenital malformation without growth potential, which
      may lead to a slow reduction of visual acuity due to secondary changes in the
      vitreoretinal interface followed by retinal traction. The hamartoma shows a
      typical clinical picture: unnoticed reduction of visual acuity, grayish tumor on
      the level of the retina with feathery margins, secondary epiretinal proliferation
      and traction of the neurosensory retina. The fluorescein angiography findings are
      pathognomonical for the hamartoma: early blockage of the choroidal
      hyperfluorescence due to the pigmentation of the tumor, a fine network of
      abnormal retinal capillaries with leakage, epiretinal traction, tortuositas of
      the larger retinal vessels without leakage. CONCLUSION: The retinal and
      pigmentepithelial hamartoma can be diagnosed in most of the cases by mere visual
      inspection. The diagnosis can be confirmed by fluorescein angiography and always
      has to be included to evaluate the differential diagnoses of all pigmented fundus
      lesions.

PMID- 8264215
TI  - [Georg Friedrich Handel's eye disease].
AB  - In his last years Georg Friedrich Handel suffered from a loss of sight not
      definitely to be defined. Based on primary sources, this disease, often mentioned
      in his biographies, is described and analysed. Altogether, Handel's eye-disease
      can be best interpreted as a central vascular disorder with degeneration of
      retina or with ischemic changes in the corresponding nuclei or tractus,
      complicated by a simple senile or post-traumatic cataract. Handel's profile of
      risk factors points most probably to a vascular degeneration of macula or a
      damage of choroidal vessels. Handel's eye-disease must be seen in relation to his
      cerebro-vascular disorder. His most probable strokes as well as his loss of sight
      were of vital importance in his biography, as is reflected even by his
      compositions. However, both disorders did not fundamentally influence his
      creativity. Only in a few compositions a reference to the loss of sight can be
      found. Apart from changes in concert-practising during his last years Handel's
      eye-disease, however, had no direct effect on his musical work.

PMID- 8264216
TI  - [Recurrent episcleritis with hyperemia of the external ear As an early symptom of
      chronic polychondritis].
AB  - A 49-year-old patient with relapsing polychondritis, who presented in the first
      instance to an eye department, is described. The patient had episcleritis,
      papilloedema and posterior scleritis. Both auricles were red, swollen and tender
      under pressure. The patient responded well to systemic steroid therapy for two
      weeks. Relapsing polychondritis is a rare connective tissue disorder. Early
      diagnosis is important, as progressive disease may cause lesions of vital organs
      (lung, heart).

PMID- 8264217
TI  - [Conceptual framework of home nursing services in Korea].

PMID- 8264219
TI  - [Community based home health care].

PMID- 8264218
TI  - [Home health care service based on the general hospital].

PMID- 8264220
TI  - [A study on the position of neonatal femoral venipuncture].

PMID- 8264221
TI  - [A study of the practice of nursing administration in a 4 year nursing education
      program].

PMID- 8264222
TI  - [Beating burnout].

PMID- 8264223
TI  - [A study on job satisfaction and its depressive factors in human relations among
      operating room nursing].
AB  - This study was done for the purpose of analyzing the job-satisfaction and its
      depressive factors in human relation of operating room nurses of university
      hospital. Therefore, it makes an offer the basic data to help the resolution and
      prevention of the problems in operating room nurses. Furthermore, this study was
      conducted in order to find out some kinds of scientific data for the better
      control of depressive factors of job-satisfaction expressed by the operating room
      nurses. The structured questionnaire reports of 246 operating room nurses who
      were employed in 5 different university hospitals which have over 1,000 beds
      located in Seoul, Korea were used, which wer collected from August 24th to August
      30th of 1992. The author visited supervisors of operating room in each university
      hospital and explained the aim of this study. The most of them (90.0%) answered
      to the questionnaires. Analysis of the collected data were done by mean, standard
      deviation, percentage, t-test, F-test, Q-test, correlation analysis, one-way
      ANOVA, and stepwise multiple regression analysis. Major findings of this study
      were as follows: 1. The job of the operating room nurses were remarkably related
      with the satisfaction in human relation, which was defined as the behavioral job
      with thoughtful action rather than with mechanical action. However, the degree of
      satisfaction in human relation with personnel in other departments was found to
      be the lowest and its the main depressive factors were appeared due to the
      absence of interaction and uncooperative attitudes. Therefore, it was required
      that the members of other job need more cooperative attitude to the actual works
      in the operating room nurses. 2. The depressive factors in the satisfaction
      degree of human relation with official seniors wer significantly related with
      their irresponsibility and partialness. Moreover, the job attitude of the
      operating room nurses is abundantly required to be improved. 3. The depressive
      factors in the satisfaction of human relation with medical doctors were
      significantly related with their insincerity and the class-consciousness. It is
      clearly suggested that the medical doctors do more cooperative behaviors for the
      jobs of the operating room without the suggested that the medical doctors do more
      cooperative behaviors for the jobs of the operating room without the superiority
      feeling of class-consciousness. 4. There was a significantly positive association
      between the satisfaction degree of human relation of the nurses with the
      following characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8264224
TI  - [Korean nurses' perception of ethical problems: toward a new code of ethics for
      nursing in Korea].

PMID- 8264225
TI  - [A study on the stress-coping pattern of head nurses].

PMID- 8264226
TI  - Tumor infiltrating lymphocytes.

PMID- 8264227
TI  - PAF molecular heterogeneity: pathobiological implications.
AB  - The existence and potential (patho)physiologic significance of PAF molecular
      heterogeneity can no longer be summarily dismissed or ignored. While significant
      advances in the chemistry of PAF have been made, the (patho)physiologic behaviors
      of most of the PAF molecular species of biologic origin await further study. This
      is because to date, investigators have studied the biologic activities of what
      was previously thought to be PAF, i.e., only 16:0- and 18:0-AGEPC. In view of the
      evidence presented in this review, a comprehensive investigation of the possible
      biologic relevance and significance of PAF molecular heterogeneity is warranted.
      Hopefully, such studies will be designed to elucidate the extent to which the
      various molecular species of PAF differ in their intrinsic in vitro and in vivo
      (patho)physiologic behaviors (agonistic, synergistic, and possibly antagonistic)
      and modes of action. Once this additional information has been derived, the
      pathobiologic relevance of this class of phospholipid autacoid may be better
      understood.

PMID- 8264228
TI  - Association between HLA-expression and infiltration of immune cells in cervical
      carcinoma.
AB  - BACKGROUND: To determine the degree of specificity of the cellular immune
      response in cervical carcinoma, that is known to be human papillomavirus-related,
      we investigated the exact relationship between in situ tumor-infiltrating immune
      cells and the monomorphic/allele-specific HLA expression on the tumor cells.
      EXPERIMENTAL DESIGN: Attention was focussed on the type, location and number of
      in situ immunocompetent cells in malignant cervical tissue (N = 30). Immune cell
      distribution was quantitatively assessed by morphometry for stromal and tumor
      tissue separately. These results were related to the degree of expression of
      monomorphic- and allele-specific HLA I and II antigens on the cervical tumor
      cells. RESULTS: In monomorphic HLA class I downregulated cervical tumors, a
      significant decrease in tumor-infiltrating CD8+ T cells was observed. However,
      allele-specific downregulation of respectively HLA-A2, HLA-A3, HLA-Bw4, and HLA
      Bw6, did not correlate significantly with a decrease in tumor-infiltrating immune
      cells. For HLA class II-positive cervical tumors, HLA-DR expression significantly
      correlated with an increase in the presence of tumor-infiltrating CD3+/CD4+/CD8+
      T cells, CD56+ natural killer cells and CD16+ macrophages. No significant
      correlations were found between alterations in HLA class I or II expression on
      the tumor cells and stromal infiltrating immune cells. CONCLUSIONS: Our
      observations provide in situ immunomorphologic evidence that in cervical
      carcinoma, de novo expression of HLA class II antigens on the tumor cells
      resulted in an increase of tumor-infiltrating immune cells. In addition, the
      tumor-infiltrating CD8+ T lymphocytes correlated with monomorphic HLA class I
      expression on the tumor cells, which stresses the existence of a HLA-restricted
      immune response of T lymphocytes in cervical carcinoma. These findings might have
      implications for the biologic behavior of this disease and have to be taken into
      account in strategies concerning immunotherapy of cervical carcinoma.

PMID- 8264229
TI  - Epidermal growth factor-like growth factors. I. Breast malignancies and other
      epithelial proliferations in transgenic mice.
AB  - BACKGROUND: Growth factors recognized by the epidermal growth factor receptor are
      important in tumor production in some organs. The family of epidermal growth
      factor-like growth factors includes a group of poxviral growth factors: Shope
      growth factor (SGF), myxoma growth factor MGF), and vaccinia growth factor. These
      viral growth factors are glycoproteins, whereas all other members of the
      epidermal growth factor family are proteins. EXPERIMENTAL DESIGN: To understand
      the potential significance of poxviral growth factors, we made transgenic mice
      using three different constructs: SGF and MGF cloned downstream from the
      metallothionein (MT) promoter (MTSGF), and SGF downstream from Rous sarcoma virus
      long terminal repeat. RESULTS: Founder transgenic mice for each construct were
      identified, and lines established. Expression of transgenes in MT-SGF mice and MT
      MGF mice was induced by feeding animals Zn at 2 months of age. Two months later,
      both MT-SGF and MT-MGF mice showed proliferation and arborization of breast ducts
      and ductules, with slight intraductal proliferation in virgin mice. They also
      showed gastric epithelial hyperplasia, particularly in MT-MGF mice. Stromal and
      epithelial hyperplasia were found in several organs. The transgenes were
      expressed in epithelia and stroma of breast, lungs, liver and stomach. Rous
      sarcoma virus long terminal repeat-SGF transgenic mice developed atypical
      preneoplastic mammary ductal proliferations in both virgin and nonvirgin females
      by 6 months of age. In 1/3 of 8-month-old females, invasive secretory
      adenocarcinoma developed. These mice also developed severe epithelial atypia in
      the stomach, and papillary gastric tumors. CONCLUSIONS: Poxviral growth factors
      may thus be helpful in the study of mammary and gastric oncogenesis and provide
      insight into growth factor-induced tumor development.

PMID- 8264230
TI  - Immunohistochemical detection of RAS, JUN, FOS, and p53 oncoprotein expression in
      human colorectal adenomas and carcinomas.
AB  - BACKGROUND: Recent evidence suggests that progressive stages of colorectal
      tumorigenesis can be defined by a sequence of genetic events characterized by
      deletion and expression of certain genes and appearance of several oncoproteins.
      Although the significance of these events is not entirely clear, oncoprotein
      expression may be directly involved in the tumorigenic mechanism. EXPERIMENTAL
      DESIGN: We examined the expression of two nuclear oncoproteins, JUN and FOS
      (Abbreviations used in this paper are lower case letters for oncogenes and upper
      case letters for oncoproteins), that have not been previously associated with
      development of colorectal cancer. This study involved detecting p39 c-JUN and p55
      c-FOS, as well as two oncoproteins previously known to be expressed during
      colorectal tumorigenesis, p21 RAS and the tumor suppressor protein, p53.
      Expression was detected with immunohistochemical methods on formalin-fixed,
      paraffin-embedded sections of normal human colons, tubular adenomas,
      tubulovillous adenomas, and adenocarcinomas. Either single oncoprotein expression
      or coexpression of four selected pairs; RAS/JUN, RAS/FOS, RAS/p53, or JUN/FOS
      were evaluated. RESULTS: We found that the expression of all four single
      oncoproteins and oncoprotein pairs were detected in very few normal colon
      specimens or tubular adenomas. However, all four oncoproteins and the four
      oncoprotein pairs were expressed significantly more often in adenocarcinomas.
      Oncogene expression in tubulovillous adenomas varied with lesion size. The number
      of lesions expressing any of the four oncoproteins or pairs was not significantly
      different than normal colon in small (< 1 cm diameter) tubulovillous adenomas.
      Significantly more large lesions (> 1 cm. diameter) expressed the single
      oncoproteins RAS, JUN, and FOS than normal colon. Of the four oncoprotein pairs,
      only RAS/JUN was significantly coexpressed in large tubulovillous adenomas.
      CONCLUSIONS: We conclude that independent expression of RAS, JUN, and FOS
      occurred significantly more often in large tubulovillous adenomas and
      adenocarcinomas while p53 expression occurred primarily in adenocarcinomas. Also,
      although all four oncoprotein pairs were expressed significantly more often in
      adenocarcinomas, only RAS/JUN was significantly coexpressed in the large
      tubulovillous adenomas. These results are comparable with the observed sequential
      activation of Ki-ras and p53 described by others and suggests that the expression
      of the nuclear oncogenes, JUN and/or FOS, are also important events in colorectal
      tumorigenesis.

PMID- 8264231
TI  - Stromal expression of platelet-derived growth factor beta-receptor and platelet
      derived growth factor B-chain in colorectal cancer.
AB  - BACKGROUND: The importance of growth factors, such as platelet-derived growth
      factor (PDGF), for stromal activation in colorectal cancer is unclear.
      EXPERIMENTAL DESIGN: The expression of beta-receptors for PDGF, and PDGF B-chain
      (PDGF AB and PDGF BB) was investigated by immunohistologic techniques in full
      thickness biopsies from 210 colorectal cancers. These antigens were detected by
      the monoclonal antibodies PDGFR-B2 and PDGF 007, respectively. RESULTS: All
      tumors contained granular clusters of PDGF beta-receptor expressing stromal
      cells, whereas tumor epithelium was invariably negative. The staining was most
      prominent in vascular cells. There were several cells in the tumor stroma that
      expressed PDGF AB/BB. Double immunofluorescence stainings in specimens from four
      patients performed in order to characterize PDGF beta-receptor- and PDGF AB/BB
      expressing cells showed that cells expressing PDGF beta-receptors did not express
      PDGF AB/BB. About 20% of cells in the stroma expressing PDGF AB/BB were
      macrophages (CD68-positive cells), whereas the nature of the remaining stromal
      cells expressing PDGF AB/BB could not be disclosed. Furthermore, about 30% of
      CD68-positive macrophages expressed PDGF AB/BB, but not PDGF beta-receptors. The
      extent of clusters of PDGF beta-receptor expressing cells varied considerably
      between tumors, and its prognostic value was considered in the entire tumor
      material. The number of clusters did, however, not correlate to tumor
      differentiation, tumor stage according to Dukes', or outcome. CONCLUSIONS: The
      presence of cells expressing PDGF beta-receptor and PDGF AB/BB respectively,
      i.e., expression of the receptor and its ligand, fulfills two of the
      prerequisites for a role of PDGF in the activation of stromal cells in colorectal
      cancers. The data suggest that stromal activation, characterized by clusters of
      PDGF beta-receptor expressing cells, is of importance for the formation of tumor
      stroma per se. However, the expression of the PDGF beta-receptor has no potential
      as a prognostic marker.

PMID- 8264232
TI  - Temporal expression of VLA-2 and modulation of its ligand specificity by rat
      glomerular epithelial cells in vitro.
AB  - BACKGROUND: The interaction of glomerular epithelial cells (GEC) with their
      underlying basement membrane is of critical importance in maintaining normal
      glomerular function. Little is known regarding their expression and use of
      extracellular matrix adhesion receptors in normal conditions and during
      pathogenic states. EXPERIMENTAL DESIGN: To examine the use of such receptors, we
      have produced monoclonal antibodies that inhibit the function of the rat alpha 2
      beta 1 integrin receptor (VLA-2) and the common beta 1 subunit. The monoclonal
      antibodies have been used to examine the expression and functional use of these
      receptors by rat glomerular cells cultured in vitro. RESULTS: Rat glomerular
      visceral epithelial cells are unusual in that, unlike many of the epithelium seen
      in vivo, these cells do not express VLA-2, an integrin receptor with affinity for
      laminin and collagen. Our results demonstrate that differentiated GEC, newly
      isolated from glomeruli, do not use VLA-2 for attachment to collagen and laminin
      coated surfaces. However, after 3 days of in vitro growth, approximately 50% of
      these cells express this receptor and, upon their first in vitro passage,
      selectively utilize VLA-2 for attachment to collagen but not to laminin-coated
      surfaces. After long-term maintenance in culture, all GEC express VLA-2, and
      utilize this receptor for binding to collagen and in their interaction with
      laminin. In contrast, VLA-2 plays only a partial role in the adherence of
      mesangial cells to collagen and is not involved in their attachment to laminin
      coated surfaces. CONCLUSIONS: These results show that, as GEC become adapted to
      in vitro growth, they begin to synthesize and use the VLA-2 integrin receptor
      suggesting a simultaneous downregulation or inactivation of other beta 1 type
      integrin receptors. This ability to modulate their receptor repertoire may allow
      GEC to respond to pathologic conditions in vivo.

PMID- 8264233
TI  - Removal systems of immunoglobulin A and immunoglobulin A containing complexes in
      IgA nephropathy and cirrhosis patients. The role of asialoglycoprotein receptors.
AB  - BACKGROUND: Whereas the complex removal routes hypothesized for IgA containing
      immune complexes (IC) and macromolecules can be adequately analyzed by a recently
      proposed IgA1-IgG aggregate probe (Lab Invest, 66: 86-95), the relative
      significance of the asialoglycoprotein receptors in IgAIC clearance is still
      uncertain. EXPERIMENTAL DESIGN: The removal kinetics of 99mTc diethylenetriamine
      pentaacetic acid-conjugated asialo alpha 1 acid glycoprotein (AAGP) and 123I
      labeled IgA1-IgG aggregate were analyzed in 11 cirrhosis patients and 13 IgAN
      patients of comparable age. RESULTS: IgA1-IgG aggregate mean plasma clearance
      rate was delayed in IgA neuropathy (IgAN) patients (slope 0.038 minutes-1, range
      0.027 to 0.053) compared with normals (0.047 minutes-1, range 0.038 to 0.053, p =
      0.05). The liver was the main organ involved in the IgA1-IgG removal. When
      compared with normals, (34.3 minutes, range 29.8 to 42.2), the liver mean transit
      time (MTT) was significantly (p < 0.02) prolonged in IgAN patients (41.3 minutes,
      33.6 to 52.3). Participation of spleen in clearance was observed in some patients
      and was almost invariably concurrent with normal clearance parameters.
      Conversely, 9 out of 11 cirrhosis patients had a remarkable splenic uptake, but
      the blood clearance rate was invariably delayed (0.022 minutes-1, 0.014 to 0.028,
      p < 0.003) and liver MTT extremely prolonged (122.4 minutes, 52.4 to 400, p <
      0.003). In IgAN patients with delayed clearance of the IgA1-IgG aggregate, a
      distinct trend of progression towards renal failure was noted. AAGP clearance was
      also delayed in cirrhosis patients: slope = 0.166 minutes-1, 0.108 to 0.247, p =
      0.05 as compared with both normals (0.230, 0.173 to 0.289) and IgAN patients
      (0.250, 0.184 to 0.254). Liver MTT in cirrhosis patients was extremely prolonged:
      240.6 minutes, 132.5 to 400 minutes, p < 0.007 compared with both normals (90.0
      minutes, 82.7 to 96.6) and IgA patients (92.2 minutes, 70.3 to 107.1). AAGP
      clearance parameters in normals and IgAN patients were not statistically
      different. MTT values of AAGP and IgA1-IgG aggregate were strictly related (p =
      0.008), suggesting that asialoglycoprotein receptors are partially involved in
      the clearance of the IgA1-IgG aggregate probe. CONCLUSIONS: Some patients with
      IgAN have a prolonged circulation of an IgAIC miming probe, probably due to an
      impaired macrophage function. Other possibilities of prolonged circulation of
      IgAIC in these patients should imply an abnormal IgA glycosylation pattern that
      allows IC to escape from an effective asialoglycoprotein receptor system. In
      cirrhosis patients, all of the removal routes of IgA and IgA containing IC are
      greatly altered suggesting a causative role in the development of an associated,
      often clinically inapparent, glomerular disease.

PMID- 8264234
TI  - Temporal central and peripheral nervous system changes induced by a paralytogenic
      mutant of Moloney murine leukemia virus TB.
AB  - BACKGROUND: The temporal localization of cellular targets for viral replication
      and the morphopathogenesis of neurodegeneration in the central nervous system
      (CNS) and peripheral nervous system induced by ts1, a neuropathogenic and
      lymphocytopathic mutant of Moloney murine leukemia virus-TB, were studied in the
      highly susceptible FVB/N mouse strain in order to better understand the
      mechanisms of this neurodegenerative disease. EXPERIMENTAL DESIGN: Newborn FVB/N
      mice were inoculated intraperitoneally with 0.1 ml of viral suspension containing
      10(6) to 10(7) infectious units/ml. The mice were observed daily for clinical
      signs of disease and killed at specific time points. Their nervous system tissues
      were collected and processed for light and electron microscopy and for
      immunohistochemical viral-antigen detection. RESULTS: ts1-Infected FVB/N mice
      developed a rapidly progressive wasting disease that culminated in hindleg
      paralysis or paraplegia 30 to 35 days postinoculation (pi). CONCLUSIONS: Clear
      evidence of CNS lesions involving the cerebellar ventricular system, the grey and
      white matter of the brain stem and the spinal cord were seen as early as 5 to 10
      days pi. These lesions, which began as mild perivascular and paraventricular
      neuropil spongiform changes and cytoplasmic vacuolation of neuronal and glial
      cell processes, progressed in severity with time and culminated in almost
      complete destruction of the white and gray matter in the brain stem and the
      cervical and lumbar spinal cord. Viruses were detected as early as 5 to 10 days
      pi in the fourth ventricle choroid plexus and ventricular lumen and budding from
      endothelial cells within the brain stem and cerebellum. Endothelial, ependymal,
      microglial, astroglial, and oligodendroglial cells were positive for gp70env.
      Astroglial and microglial cell proliferation with microglial syncytia formation
      was detected only within the areas showing spongiform degeneration. Viral
      replication was consistently high in the capillary endothelial cells of those
      areas showing spongiform degeneration, whereas in the glial cells, relatively few
      budding viruses were present. Neurodegeneration was accompanied by
      demyelinization within the CNS and peripheral nervous system and by hindleg
      muscle degeneration and necrosis. Multiple cellular targets for ts1 viral
      infection and replication were detected within the nervous system. The presence
      of budding virus and the immunodetection of viral antigen in the choroid plexus
      and ependymal cells of the fourth ventricle and the central canal of the spinal
      cord demonstrated that cerebrospinal fluid as well as blood can disseminate virus
      within the CNS. Pathologic and functional changes within the blood-brain barrier
      and glial system probably account for the neuronal necrosis and spongiform
      changes that result in paralysis induced by ts1 infection.

PMID- 8264235
TI  - Expression of Lyn protein on human malignant lymphomas.
AB  - BACKGROUND: lyn is one of the src family genes encoding protein-tyrosine kinases,
      expressed preferentially in B lymphocytes and monocytes/macrophages. Its gene
      product, Lyn protein, is thought to participate in cell membrane-associated
      signal transduction on B lymphocytes by associating physically and functionally
      with membrane-bound IgM. EXPERIMENTAL DESIGN: To investigate the expression of
      Lyn on human malignant lymphomas (MLs), 50 ML biopsies, 12 ML samples maintained
      in mice with severe combined immunodeficiency, and 4 African Burkitt type cell
      lines were studied with the use of immunohistology, immunochemistry, and Southern
      blot analysis. RESULTS: Among biopsy specimens, 27 of 27 B-MLs, 5 of 21 T-MLs,
      and 2 of 2 null-MLs were stained. In severe combined immunodeficiency mouse
      maintained B-MLs, unlike biopsied B-MLs, 4 of 11 were found to be unstained.
      Further analysis disclosed that all 4 of these unstained B-MLs were the Epstein
      Barr virus transformed B cells proliferating in severe combined immunodeficiency
      mice and not the original ML cells, suggesting the presence of a specific
      mechanism down-regulating the Lyn protein in this group. One IgA+ IgM- B-ML and
      one IgG+ IgM- B-ML were stained by the antibody, indicating the possible
      existence of molecular mechanisms other than membrane-bound IgM that facilitate
      Lyn protein expression. Decrease of Lyn expression was also noted in 3 of 4
      Epstein-Barr virus-positive African Burkitt's ML lines. Complementary Western
      blot analysis of 8 immunostained and 4 unstained MLs confirmed the
      immunohistologic findings. However Southern blot analysis showed that the lyn
      gene in Lyn-positive and -negative cases were apparently unchanged. CONCLUSIONS:
      The level of Lyn expression in MLs reflects mainly their normal counterpart,
      whereas it can be expressed somewhat differently in some cases, especially in
      Epstein Barr virus-transformed MLs that occur in immunocompromised hosts, on
      which it is often down-regulated. This is the first report of Lyn expression on
      human MLs.

PMID- 8264236
TI  - Detection of neuron-specific gamma-enolase messenger ribonucleic acid in normal
      human leukocytes by polymerase chain reaction amplification with nested primers.
AB  - BACKGROUND: NNE (non-neuronal alpha-enolase) is a glycolytic enzyme detected in
      most tissues. NSE (neuron-specific gamma-enolase) is detected in normal neurons
      and tumors such as neuroblastoma. Staining with antibodies against NSE is
      therefore used to detect neuroblastoma cells invading bone marrow. Since staining
      of normal leukocytes has been reported we asked whether bona fide NSE is in fact
      expressed in normal blood and marrow. EXPERIMENTAL DESIGN: We designed nested
      coding region specific primers for NSE and NNE and, after reverse transcription
      of mRNA, we amplified the coding region between these primers in a semi-nested
      polymerase chain reaction. In order to distinguish both iso-mRNAs from each
      other, we amplified a long (1,047 bp) template in a first round of 30 cycles with
      primers specific for NNE or NSE. One percent of this product was used in a second
      round of 30 cycles in which both sense primers and two nested anti-sense primers
      of alternate specificities yielding shorter products of discernible sizes (768 bp
      or 619 bp) were added together in the same reaction tube. With this combination
      of four primers, only that shorter product was amplified to visibility, the
      specificity of which was homologous to the template produced in the first 30
      cycles. Restriction enzyme digestion of the amplified products was used to verify
      this polymerase chain reaction-based approach for the distinction of isoforms of
      RNA. RESULTS: This semi-nested polymerase chain reaction clearly allows for the
      distinction of mRNA for NNE or NSE and shows the presence of transcripts for NSE
      in normal human leukocytes from blood and bone marrow. CONCLUSIONS: This method
      exploiting short stretches of nucleotide differences in the coding regions for
      priming can more generally be applied to the distinction of all isoforms of RNA
      where nested specific primers can be designed. However, the presence of NSE
      specific transcripts in normal human leukocytes invalidates the use of this
      highly sensitive method as a disease marker in neuroblastoma.

PMID- 8264237
TI  - Endothelin-1 secretion by human gallbladder epithelial cells in primary culture.
AB  - BACKGROUND: The three isoforms of endothelin (ET), ET-1, ET-2, and ET-3 are
      potent contractile agonists for smooth muscle in a wide variety of tissues
      including the gallbladder. There is increasing evidence that endothelin acts in a
      paracrine fashion, however, its cell source in the gallbladder is unclear.
      EXPERIMENTAL DESIGN: To examine the production of ET by gallbladder and bile duct
      epithelium. RESULTS: We show that human gallbladder epithelial cells in primary
      culture secrete endothelin. ET release was time-dependent, and intracellular ET
      was negligible, indicating de novo synthesis. Secretion was increased by
      physiologic concentrations of cholecystokinin. Epithelial cells lining hepatic
      cysts in primary culture also released ET, suggesting that the intrahepatic, as
      well as the extrahepatic biliary epithelium is a source of this cytokine. High
      performance liquid chromatography separation of the conditioned medium from both
      cell types showed a single peak corresponding to that of ET-1. In vivo, ET-1 was
      present in hepatic cyst fluid, but was not detectable in gallbladder or
      choledochal bile. On tissue sections, both intrahepatic and extrahepatic bile
      duct epithelial cells were labeled with an anti-"big" ET-1 polyclonal antibody.
      CONCLUSIONS: These results suggest that ET-1 is locally produced in the biliary
      tract and by a paracrine route, could play a role in choledochal motility and
      gallbladder contraction.

PMID- 8264238
TI  - Insulin-like growth factor-1 and its receptor mediate the autocrine proliferation
      of human ovarian carcinoma cell lines.
AB  - BACKGROUND: IGF-1 regulates the growth of diverse mammalian cell types including
      several human carcinoma cell lines. The IGF-1 receptor is a glycosylated
      heterodimer which, upon binding with IGF-1, undergoes tyrosine
      autophosphorylation. The autophosphorylation of the beta-receptor subunit is a
      strict requirement for its mitogenic properties. EXPERIMENTAL DESIGN: In this
      study, we have assessed the role of the IGF-1 receptor in the proliferation of
      ovarian carcinoma cell lines in culture. Effects of anti-sense and sense
      oligodeoxynucleotides to IGF-1 receptor RNA were tested. RESULTS: The human
      ovarian carcinoma cell lines OVCAR-3 and CaOV-3 both grew autonomously in serum
      free medium, and their growth was further stimulated by the addition of IGF-1.
      Incubation of cells with anti-sense oligodeoxynucleotides corresponding to the
      IGF-1 receptor RNA markedly inhibited cell proliferation both in serum-free
      medium and in the presence of IGF-1. The inhibition of cell growth by the
      oligodeoxynucleotides corresponded to a reduction in the amount of detectable
      phosphorylated IGF-1 receptor. CONCLUSIONS: The findings indicate that IGF-1 and
      its specific receptor mediate the autocrine proliferation of human ovarian
      carcinoma cell lines.

PMID- 8264239
TI  - Gametic imprinting as a speciation mechanism in mammals.
AB  - Gametic imprinting renders mammalian male and female genomes functionally
      hemizygous at specific loci. Successful embryogenesis can only be accomplished in
      the presence of both parental genomes. The mechanism of gametic imprinting is at
      present unknown, although circumstantial evidence suggests it is similar in
      nature to X inactivation. A model is presented which describes the effects of
      switching the imprint pattern at male and female target genes. The consequence of
      such an event is reproductive isolation, and could lead to the formation of a new
      species.

PMID- 8264240
TI  - Melanocytes as "sensory" and regulatory cells in the epidermis.
AB  - Epidermal melanocytes (MC) are pigment-producing and secretorily active cells of
      neural crest origin that communicate directly with multiple targets. Here, we
      propose that normal epidermal MC also are "sensory" and regulatory cells
      operating in the context of a regulatory network for the maintenance of human
      epidermal homeostasis. Altered regulatory MC functions may play a role in
      selected skin diseases, and racial pigmentation may affect cutaneous functions.

PMID- 8264241
TI  - Structure-induced strain determining the internal cyclization site in the yeast
      cobI5 autocatalytic intron: theory and experimental tests.
AB  - The terminal intron of the apocytochrome b gene of yeast is endowed with
      autocatalytic potential in vitro and has been also shown to be capable of
      internal circularization at the linkage 236-237 from the 5' extremity. The aim of
      this work is to identify the secondary interaction responsible for shaping and
      activating the internal cyclization site (ICS). This is done by simulating the
      sequential folding of an abnormally large fragment of 237 nucleotides which
      starts at the 5' cleavage site and contains the internal guide sequence (IGS)
      starting 220 nucleotides into the intron. The resulting portion of the overall
      structure features the conserved interaction P1 and is compatible with the
      complete consensus secondary structure for this intron. The structural motif
      which emerges from sequential folding and is responsible for shaping the ICS is
      confirmed by analyzing the localization of structure-induced strain in the RNA
      backbone. It is shown that after the conserved stem P1 has been dismantled, the
      highest strain in a phosphodiester linkage is localized internally precisely at
      the experimentally determined cyclization site. Moreover, it is shown that our
      dynamical model of folding is compatible with the actual reaction pathways. Thus,
      internal cyclization becomes feasible only after conserved interaction P1 has
      been dismantled. This last event, in turn, might take place as a consequence of
      either of the following events: (i) 5' cleavage caused by nucleophilic attack by
      the GTP-cosubstrate or (ii) excision of the 3' exon after prior formation of P10.
      This last event, in turn, requires dismantling helix P1. Moreover, event (ii) is
      necessary for internal circularization since it habilitates the 3' terminal
      guanosine as a nucleophilic agent.

PMID- 8264243
TI  - Somatic hypermutation in B cells: an optimal control treatment.
AB  - The vertebrate immune system generates high-affinity antibodies to external
      antigens through a process of somatic hypermutation that takes place in germinal
      centers formed in the secondary lymphoid tissues. B cells proliferating in these
      germinal centers experience random mutations in the genes encoding the variable
      region of their immunoglobulin molecules and are subsequently selected for high
      affinity binding to antigen. These germinal center reactions last for only about
      2 weeks, yet in that time typically produce multiple point mutations resulting in
      affinity increases of factors of ten to a hundred or more. We have attempted to
      understand this extraordinary effectiveness by causing the problem of affinity
      maturation as an optimization problem in which a quantity that we call the total
      affinity is maximized as a functional of mu(t), the mutation rate as a function
      of time. We have developed a single-compartment model for the process and an
      optimization algorithm based on the Pontryagin maximum principle. Our results
      show that the optimum mutation schedule is one with brief bursts of high mutation
      rates interspersed between periods of mutation-free growth. Though this result at
      first seems highly non-physiological, we show that, in fact, it provides a
      framework within which the anatomy and kinetics of the germinal center reaction
      can be understood.

PMID- 8264242
TI  - Pressure changes in the eye due to an injection of inert gases: a theoretical
      model.
AB  - In the repair of retinal tears and detachments, the vitreous humor is often
      completely replaced with a temporary mixture of gases, one of which is not
      normally found in the bloodstream. The resulting bubble can then support the
      healing retina. There is diffusion of gases, however, from the bubble into the
      bloodstream and vice versa. This alters the intraocular pressure, with possible
      adverse consequences, as the intraocular pressure must be maintained within a
      certain range for the procedure to be successful. A simple model has been
      developed to predict the evolution of intraocular pressure over time, given a
      certain initial mixture of injected gases. This model could be useful in
      determining what mixture to use to support effectively and safely a healing
      retina.

PMID- 8264244
TI  - Deriving an amino acid distance matrix.
AB  - Various methods were investigated to convert an amino acid similarity matrix into
      a low-dimensional, metric distance matrix. Using projection techniques, no unique
      transformation was found and of the many inversion forms investigated, simple
      negation normalized by the diagonal elements produced a good fit to the original
      data. An inter-row distance also gave a comparable fit and when evaluated by
      weighted least-squares minimization was found to be preferable. A rank-ordered
      form of the matrices was also derived by constraining neighbours to be
      equidistant in 3D-space. This produced a network configuration not unlike that
      produced in a previous analysis of amino acid physicochemical properties. The
      derived forms might find applications in sequence alignment, including pattern
      matching algorithms, and the construction of phylogenetic trees.

PMID- 8264245
TI  - A second-order approach to metabolic control analysis.
AB  - In the mathematical formalism of metabolic control analysis the changes in
      metabolite concentrations and fluxes have been related to the underlying
      parameter perturbations by a linear approximation, thus restricting the analysis
      to very small parameter perturbations. Obviously, the response of the system
      variables to larger parameter perturbations can be described more accurately if,
      in addition to the linear terms, the second-order terms are considered. The basic
      equations of this approach are derived. The second-order effects can be expressed
      (i) by the second-order elasticity coefficients of the reaction rates with
      respect to the kinetic parameters and/or metabolite concentrations, and (ii) by
      the control coefficients and pi-elasticities of the linear theory. Parameter
      independent second-order control coefficients can be defined if the reaction
      rates depend linearly on the perturbation parameters. These coefficients satisfy
      summation theorems similar to those of the linear theory. The formalism is
      applied to an unbranched chain of monomolecular reactions and to a skeleton model
      of glycolysis. The second-order approximation turns out to be more accurate for a
      relatively wide range of rate perturbations. However, the use of the second- and
      higher-order expansions for tackling practical problems seems limited since the
      required higher-order elasticity coefficients may be hard, if not impossible, to
      obtain experimentally. These difficulties, as well as the general limitations of
      the local approach of metabolic control analysis, may be compensated for by a
      combination with kinetic modelling.

PMID- 8264246
TI  - The origin of chromosomes. I. Selection for linkage.
AB  - A model is analysed of cells containing independently replicating genes, which
      segregate randomly when the cell divides. We follow the fate of a primitive
      chromosome, in which two genes are linked, so that they replicate and segregate
      together. Such a chromosome increases in frequency in the population provided
      that (i) the two genes act synergistically, so that a cell containing at least
      one copy of each grows faster than a cell lacking one or other, and (ii) the
      number of genes per cell is small. The increase in frequency occurs even if the
      chromosome takes twice as long as an individual gene to replicate, giving a two
      fold selective disadvantage within a cell. The increase occurs because a gene
      that is linked does not run the risk of finding itself, in the next generation,
      in a cell that lacks its synergistic partner.

PMID- 8264247
TI  - The effects of unequal sister chromatid exchange on length of arrays of repeated
      sequences.
AB  - Models of homogenization of repeated sequences by unequal sister chromatid
      exchange (USCE) assume that no significant changes in array length occur. The
      effects of successive USCEs on the lengths of arrays of repeated sequences has
      been examined mathematically and by simulation, assuming misalignment to be
      greater in longer arrays, a condition necessary for homogenization. The series of
      duplications and deletions gives a wide, asymmetric variation in copy number.
      Frequencies follow a binomial distribution, but if misalignment increases with
      array length, lengths become logarithmically distributed, most arrays being
      shorter than the original, counterbalanced by a few very long arrays. The median
      length, which is also the modal length, decreases exponentially or
      asymptotically. Given a proportional misalignment of a, the median (mode)
      decreases by a2/2 per unequal crossover. Since drift is a random transmission of
      available alleles in the population, it follows that fixation of common short
      arrays is much more probable than fixation of rare long arrays. This process will
      continue inexorably until each array is too short to undergo further unequal
      crossing over, and no more variation is generated. The number of unequal
      crossovers required by some published models of homogenization would almost
      certainly cause dramatic reduction in number, or complete loss, of repeats.
      Frequent unequal sister chromatid exchanges are not compatible with survival of
      arrays unless counteracted by an independent amplification mechanism or
      selection, so are unlikely to be important as a long-term homogenization
      mechanism in non-essential repeated sequences.

PMID- 8264248
TI  - Memory to antigenic challenge of the immune system: synergy of idiotypic
      interactions and memory B cells.
AB  - Memory to antigenic challenge of the immune system is described as a synergy of
      two components: cycles of interacting B cells in a dynamic equilibrium which
      store an internal image of an antigen, and long-lived memory B cells which
      stabilize the cycle that generates them. Small cycles are most relevant to the
      immune system's memory. The network is globally stable and supports Jerne's idea
      that suppression is important. Our model allows for exponential increase of
      antigens during the initial stage of infection. It has a number of stable fixed
      points, viz the virgin state, the healthy immunized state, and a state of chronic
      infection, the last occurring if the antigen is virulent enough. Numerical
      simulations show a difference between primary and secondary response and exhibit
      both predator-prey and intracycle oscillations. In the case of a chronic
      infection, the simulations suggest a specific stimulation therapy triggered by
      repeatedly injecting the antigens, thus making the infection acute. An optimal
      therapy is indicated.

PMID- 8264249
TI  - Metabolic control design.
AB  - The response of metabolic variables to small parameter changes is quantitatively
      described by the control coefficients. Their values (the control profile) depend
      on the rate equations of the enzymes which compose the metabolic system. A
      procedure, called Metabolic Control Design (MCD), is developed which achieves the
      "inverse", namely to calculate the kinetic properties of the enzymes which would
      produce a preconceived control profile when they are embedded in the network. It
      is shown that the lack of interaction between some variable metabolites and
      enzymes (i.e. some epsilon-elasticity coefficients are zero), together with the
      well-known conservation and summation relationships, reduce the number of control
      coefficients to which arbitrary values can be assigned. A choice of the values of
      these coefficients constitutes the pre-established control profile. The same
      procedure can also be used as an in situ method to detect unknown interactions
      between enzymes and metabolites. Finally, we discuss some implications of the
      results to the evolution of living organisms.

PMID- 8264250
TI  - Presence as a nursing intervention with hospitalized children.
AB  - A review of nursing literature indicates that presence is a widely accepted
      nursing intervention, yet very little discussion exists regarding nursing
      presence as an intervention with children. The author's purpose is to discuss the
      importance of nursing presence with children, provide information on ways in
      which nurses can operationalize and evaluate presence, and identify implications
      for needed research on presence with children.

PMID- 8264251
TI  - Effects of home visits and telephone contacts on breastfeeding compliance in
      Taiwan.
AB  - The purpose of this quasi-experimental study was to test the effects of home
      visits and telephone contacts on mothers' compliance to breastfeeding in Taiwan.
      A total of 180 mothers was assigned to three groups: home visit, telephone
      contact, and control. No significant differences were found between groups.
      However, multiparas showed a significantly longer duration of breastfeeding and a
      more positive experience of breastfeeding than primiparas. The best subsets to
      predict breastfeeding duration were level of breastfeeding easiness and a home
      visit, which accounted for 20% of the total variance.

PMID- 8264252
TI  - Social support and the early maternal experience of primiparas over 35.
AB  - Social support and the early maternal experience were examined in 91 first-time
      mothers over 35 years of age, using the Norbeck Social Support Questionnaire
      (Norbeck, Lindsey, & Carrieri, 1981, 1983) Parenting Support Questions, the
      Parenting Network Scale, and the What Being the Parent of a Baby is Like Scale
      (Pridham & Chang, 1989). Data were collected in the last trimester of pregnancy
      and at 1 month postpartum. The greatest amount of support came from spouse,
      friends, and family. Subtle changes occurred in social support with decreases in
      number of network members and functional scores, and increases in number of
      members with children under 2 years of age. Social support from spouse and family
      was associated with both positive self-evaluation in parenting and lower stress
      postpartum.

PMID- 8264253
TI  - Paternal perspectives of the childbirth experience.
AB  - This study examined the responses given by first-time fathers who were asked to
      describe their feelings about their childbirth experience. The fathers answered
      three open-ended questions about their feelings concerning labor and childbirth,
      and the paternal behaviors believed to be most useful to their wives during labor
      and delivery. Data from fathers who attended prenatal childbirth education
      classes were examined separately from fathers who did not attend. The findings
      indicated that for all fathers, regardless of prenatal preparation, the labor
      experience evoked generally positive responses in addition to a significant
      number of negative responses, while perceptions of the birth experience were
      primarily characterized by positive or very positive feelings. The results also
      indicated that the fathers perceived that they were most helpful to their partner
      during labor.

PMID- 8264254
TI  - Low dose cyclophosphamide, alpha-interferon and continuous infusions of
      interleukin-2 in advanced renal cell carcinoma.
AB  - Pretreatment with a low dose of cyclophosphamide (CY) has been claimed to inhibit
      suppressor functions and augment various immune functions. A combination of a low
      dose of CY, alpha-interferon (IFN-alpha) and continuous infusion of interleukin-2
      (IL-2) was used to treat patients with advanced renal cell cancer (RCC) (stage
      IV). Sixteen patients received four cycles consisting of CY (500 mg m-2) three
      days prior to daily i.m. injections of alpha-IFN (3 x 10(6) U), and continuous
      infusion of 18 x 10(6) IU rIL-2 for five days. The cycle interval was three
      weeks. Two patients had partial response (13%) (26+ and 12+ months), two had a
      minor response (9+ and 4 months), and three patients achieved stable disease
      (19+, 14+ and 8+ months). No patients required intensive care. Side effects were
      mainly fever, malaise, capillary leak syndrome and diarrhoea. Non-responders
      showed significantly higher eosinophil and platelet counts compared to
      responders. Serum concentration of IL-2 was significantly higher in responders.
      5/11 patients had abnormally low values of serum thyroxine after therapy. Two
      patients needed thyroid hormone substitution. The difference between the initial
      and the lowest thyroxine values correlated significantly to survival (p < 0.03).
      The addition of CY to rIL-2 and IFN-alpha in the present protocol did not
      contribute to an increased major response rate.

PMID- 8264255
TI  - T-lymphocyte sub-populations in orbito-ocular granulocytic sarcoma (OOGS) and
      acute myelocytic leukemia (AML): a preliminary study.
AB  - The aetiology of GS remains obscure and a little is known about the immune
      competence of these patients. Interestingly, all children with OOGS were from low
      'socio-economic status' and showed diminished delayed hypersensitivity reactions
      and reduced T cell counts (E-R) in our previous observation. We present herewith
      a preliminary data on evaluation of T cell sub-populations determined by
      monoclonal antibodies (CD3, CD4, CD8 and CD16 cells) in 10 patients with OOGS and
      AML prior to treatment. Quantitative immunoglobulin determinations of IgA, IgM,
      IgG were also made. The percentage of Pan T (CD3), CD4, CD8 cells were
      significantly lower than those in the controls (p < 0.01). The immunoglobulin
      levels were slightly elevated suggesting normal B cell functions. In conclusion,
      these preliminary findings suggest that cellular immune deficiency may be an
      underlying cause.

PMID- 8264256
TI  - Ultrastructural investigation of DNA in megakaryoblastic leukemia by using osmium
      ammine-B: comparison with several types of leukemia.
AB  - Using DNA staining with highly stable osmium-ammine-B, the blasts of AMKL were
      observed under an electron microscope, in comparison with AML, ALL, CML-MK crisis
      and TMD. The DNA within the nucleus of the megakaryoblasts was observed as a high
      electron-density substance and tended to be uniformly dispersed within the
      nucleus. DNA, associated with nucleoli, could be roughly divided in four types
      based on the presence or absence of peri-nucleolar clumps and intra-nucleolar
      clumps. In cases of AMKL, we often observed a type that did not have peri
      nucleolar DNA clumps but did have DNA flecks within the nucleoli. By analytical
      evaluation there were no differences among cells from several subtypes of
      megakaryocytic leukemia, such as AMKL in children with Down's syndrome, AMKL in
      children without Down's syndrome, AMKL in adults, and CML-MK crisis. The DNA
      distribution of TMD blasts, which were self-limited and not malignant, resembled
      that of AMKL blasts.

PMID- 8264257
TI  - Expression of an adhesion molecule and homing in B-cell chronic lymphocytic
      leukaemia: I. Application of the HEV-binding assay to a clinical series.
AB  - High endothelial venule (HEV)-binding of peripheral blood mononuclear cells
      (PBMCs) from 43 patients with B-cell chronic lymphocytic leukaemia (B-CLL) was
      investigated with a HEV-binding in vitro assay. Immunophenotyping of HEV-adherent
      PBMCs proved that most of them belonged to the B-cell proliferation. B-CLL cells
      stringently expressed CD44 molecules (Hermes-1, -3 and H90). The patients were
      subgrouped according to Binet's classification, as well as according to the organ
      manifestations, i.e. patients with B-cell monoclonal lymphocytosis of
      undetermined significance (B-MLUS) and patients with lymphocytosis (LY), lymph
      node enlargement (LN) and splenomegaly (SM). The HEV-binding activity of the
      cells was the highest in Binet stage A patients and in patients with B-MLUS (p <
      0.05 in B-MLUS versus B-CLL LY, LN, SM). Based on these findings it is suggested
      that B-CLL patients show not only a clinical and immunophenotypical
      heterogeneity, but a diverse function of adhesion molecules.

PMID- 8264258
TI  - Clinical evaluation of the CORDIS vascular access port systems: a multicenter
      study.
AB  - Two non-metallic vascular access port systems, the Multipurpose Access Port
      (MPAP) and Miniport, developed by CORDIS S.A., France, have been evaluated
      clinically in 78 cancer patients. During the investigational period covering a
      total experience of 369 treatment cycles and 1,370 infusion days, no cases of
      infection or septicemia were observed. Serious complications such as drug
      extravasation and catheter occlusion occurred, although the incidence was
      relatively low (+/- 1%) when compared with the number of treatment courses
      (cycles), but in relation to the number of patients included in this study, the
      procedure-related complication rate was 17.5% for the MPAP and 15.8% for the
      Miniport. Procedure-related complications can be avoided by proper handling and
      use of suitable drug combinations to minimize crystallization reactions within
      the port-catheter systems. The final complication rate (total minus procedure
      related) in terms of termination of treatment, i.e. explantation of the port
      catheter system was 12.1% for the MPAP and 12.5% for the MINIPORT, which
      generally confirms the results of other groups. More than 87% of both port
      catheter systems were still functional at the end of evaluation.

PMID- 8264259
TI  - Treatment of ovarian cancer: the state of the art.
AB  - The state of the art in the treatment of ovarian cancer is reviewed. Development
      in strategies for early and advanced ovarian cancer stages as well as prospects
      for the future are described.

PMID- 8264260
TI  - [Occupational health services in the future. Will they be performed by the
      general practitioner or an occupational health specialist?].

PMID- 8264261
TI  - [Delayed surgery for ulcer is dangerous].

PMID- 8264262
TI  - [Education about unemployment?].

PMID- 8264263
TI  - [New uncertainties about brain death criteria].

PMID- 8264264
TI  - [Smoking and goiter. Sex, heredity and stress are stronger risk factors].

PMID- 8264265
TI  - [Diagnosis of sinusitis].

PMID- 8264266
TI  - [Eye discomfort when working with video display terminal. Big differences
      depending on the type of work].

PMID- 8264267
TI  - [Anorexia and bulimia. Intensive research work is necessary--fundamental
      questions are still not solved].

PMID- 8264268
TI  - [Functional endoscopic sinus surgery. A considerate treatment in chronic
      sinusitis].

PMID- 8264269
TI  - [Report of a case: hepatic failure after treatment with interferon].

PMID- 8264270
TI  - [Oxygen--when, why, how? Treatment of chronic hypoxia and other lung diseases].

PMID- 8264271
TI  - [Lymphocyte migration and recirculation. Functional and diagnostic aspects].

PMID- 8264272
TI  - [How important is following the physician's instructions? Demands on patients
      vary among different individual groups].

PMID- 8264273
TI  - [Rationing benefits, public health, holistic view. Arguments for development of
      primary health care 1934-1968].

PMID- 8264274
TI  - [Primary health care in Sweden and Norway? How to explain the different
      development?].

PMID- 8264275
TI  - [We have been too obliging. Others decide for the general practitioners].

PMID- 8264276
TI  - [Shortage of physicians interested in primary health care. The profession
      concentrates more on specialization].

PMID- 8264277
TI  - [Pain relief in rheumatoid arthritis. Dietary factors can influence the
      rheumatoid inflammation].

PMID- 8264278
TI  - [SWEDOP--a program for registration of complications. Does increased awareness
      mean lower number of complications?].

PMID- 8264279
TI  - [Women physicians are getting stronger in their leadership role. "Bumble-bee"--a
      project for better occupational environment].

PMID- 8264280
TI  - [The National Board of Health and Welfare on the laws in psychiatry. About 50
      patients may be committed illegally].

PMID- 8264281
TI  - [Quality assurance in psychiatry: how do we manage new patients, involuntary
      commitment and attempted suicides?].

PMID- 8264282
TI  - [Prevention and early diagnosis of cancer. Role of primary health care facing the
      reform of family practice].

PMID- 8264283
TI  - [Investigation minimizes a severe handicap: it's wrong to set a low priority on
      unwanted sterility].

PMID- 8264284
TI  - [Drug handling is unreasonable in Sweden].

PMID- 8264285
TI  - [Is it time to exclude interns from health care centers?].

PMID- 8264286
TI  - [Health insurance and certification fees].

PMID- 8264287
TI  - [Medical education, present and future].

PMID- 8264288
TI  - [Torsades de pointes--a rare (?) and unpredictable arrhythmia].

PMID- 8264289
TI  - [The human genome project. Report on the current status].

PMID- 8264290
TI  - [Sodium channels and anti-arrhythmia agents. Time for a new classification?].

PMID- 8264292
TI  - [Why don't you come when I am crying? The shrieking infant].

PMID- 8264291
TI  - [The anorectic family--an old-fashioned concept].
AB  - The article updates Yager's 1982 review of familial factors in the pathogenesis
      of anorexia nervosa. The concept of "the anorectic family", as used by Minuchin
      and co-workers, although adequately describing a subgroup of families with an
      anorectic family member, is not a valid description of the group as a whole. No
      constellation of familial factors has been shown to be characteristic of the
      families of all anorexia patients. However, certain familial factors have been
      shown to be over-represented-e g, the presence of eating disorders, affective
      illness and alcoholism among close relative. Such "serious life events" as the
      loss of a close relative have also been shown to be over-represented among
      teenage girls with anorexia nervosa. The importance of these findings in
      connection with history taking is discussed. Future research should be designed
      to identify subgroups of anorexia nervosa patients for whom familial factors are
      of special significance, instead of treating anorexia nervosa as a uniform entity
      where the same set of aetiological factors (either genetic, psychological or
      interpersonal) are valid for all cases.

PMID- 8264293
TI  - [A case report. Herpes gladiatorum in a boy who is not a wrestler].

PMID- 8264294
TI  - [Autistic syndrome. A concern also in adult psychiatry].

PMID- 8264296
TI  - [Psychiatric rehabilitation. Philosophy and practice in a sector of social
      psychiatry].

PMID- 8264295
TI  - [Acute coronary syndromes. Simplified routines with early exercise test performed
      at the intensive coronary care units].

PMID- 8264297
TI  - [Social service and psychiatry. Cooperation is necessary for progress].

PMID- 8264298
TI  - [Motivation and care of alcohol abuse. A new method increases therapeutic
      efficiency].

PMID- 8264299
TI  - [Surgery or not in reflux?].

PMID- 8264300
TI  - [A consensus statement. Remove the uterus? Causes, methods, alternatives].

PMID- 8264301
TI  - [Stop the cholesterol campaign!].

PMID- 8264302
TI  - [Equality and solidarity are not economical concepts. Freedom of choice and
      efficiency may conceal needs].

PMID- 8264303
TI  - [Dangerous leadership and mobbing at work].

PMID- 8264304
TI  - [Work satisfaction in health care].

PMID- 8264305
TI  - [No true picture of current medical education].

PMID- 8264306
TI  - [Uncritical about critical thinking?].

PMID- 8264307
TI  - [Clinical social medicine in the 90's].

PMID- 8264308
TI  - [Does reformed family practice equal cutting down in sparsely populated areas?].

PMID- 8264309
TI  - [ST analysis after myocardial infarction--ambulatory ECG registration?].

PMID- 8264311
TI  - [The Medical Product Agency sharpens its control. What is the consequence of bad
      trials?].

PMID- 8264310
TI  - [Intoxication and inspiration seen from a molecular point of view].

PMID- 8264312
TI  - [Conclusion from a follow-up by the National Board of Social Welfare. Necessity
      for change in the commitment laws].

PMID- 8264313
TI  - [Chemoprevention of cancer].

PMID- 8264314
TI  - [Graves' disease. History of a restored eponym].

PMID- 8264315
TI  - [What does a limp mean?].

PMID- 8264316
TI  - [Leprosy can be eliminated as a public health problem].

PMID- 8264317
TI  - [Light-skinned women and dark-skinned men in art. Does this reflect real
      differences in skin pigmentation?].

PMID- 8264318
TI  - [Creative inebriation from Odin to Ekelof].

PMID- 8264319
TI  - [The ship's doctor who wrote his life and cursed his colleagues].

PMID- 8264320
TI  - MRI guided interstitial laser therapy in a rat malignant glioma model.
AB  - We have used MR monitoring to guide and evaluate the effects of the Nd:YAG
      interstitial laser on a well-characterized rat brain tumor model (C6). MRI was
      used to determine the tumor size, verify the location of the interstitial probe,
      and evaluate the size and location of the laser-induced lesion during and after
      treatment. During laser irradiation, an irreversible loss of signal intensity at
      the fiber tip and a reversible decrease in signal intensity around it were
      observed with MRI. None of the treatment protocols affected mean rat survival
      significantly. Although MRI-guided interstitial laser therapy appears to be safe
      and easy, it does not provide a curative treatment for spatially disseminated
      gliomas where a "target volume" cannot be adequately defined. Better results can
      be expected, especially in well-defined tumors, with improvements of both the
      imaging techniques and the laser treatment protocol.

PMID- 8264321
TI  - Low-level CO2 laser-induced release of 51chromium from canine 2C5 gliosarcoma
      cells.
AB  - Recently, interest has grown in the area of low-power laser effects upon tissues.
      We used a 51Cr cell labeling technique with glioma tissue to better understand
      these effects. Canine 2C5 gliosarcoma cells with intracellular 51Cr were exposed
      to CO2 laser in the range of 0.2 to 3.0 J/cm2. Correlative analysis of the data
      indicated that there is a strong direct relationship between laser fluence and
      the percent of total intracellular 51Cr released from the glioma cells with a
      coefficient of correlation (r) of +0.93. The calculated standard error of the
      correlation coefficient was +/- 0.06 and the coefficient of determination (r2)
      was 0.86. These results indicate that the 51Cr cell labeling technique is a
      useful method for quantifying the low-power laser effects on the integrity of the
      cell membrane of gliosarcoma cells in vitro. However, further investigation is
      needed to clarify the specific mechanisms by which the CO2 laser induces changes
      upon these cells.

PMID- 8264322
TI  - Photodynamic activity of liposome-delivered Cd-texaphyrin using tumor-bearing
      nude mice.
AB  - Photodynamic effects in bladder-tumor bearing nude mice induced by a krypton ion
      laser (752.5 nm) after i.v. application of liposome-delivered cadmium texaphyrin
      were investigated. Cd-texaphyrin possesses strong absorption transitions in the
      far red spectral region (around 760 nm) and a high quantum efficiency of singlet
      oxygen production. No therapeutic effects were obtained using irradiation 24
      hours after administration of the sensitizer, whereas phototreatment 2 hours
      after application led to significant tumor reduction. This corresponds well with
      studies on fluorophore-labeled liposomes indicating highest tumor accumulation 1
      2 hours after administration. However, the induced cytotoxic effects were lower
      than those of HpD.

PMID- 8264323
TI  - Soft tissue studies with 805 nm diode laser radiation: thermal effects with
      contact tips and comparison with effects of 1064 nm Nd:YAG laser radiation.
AB  - This study compares the perioperative depths of thermal coagulation, charring,
      and incision in rabbit liver, internal anterior abdominal wall skeletal muscle,
      and abdominal skin and in swine liver and abdominal skin obtained with 805 nm
      diode laser and 1,064 nm Nd:YAG laser radiation using 300-microns-diameter
      conical-tip and 1,200-microns-diameter spherical-tip contact fibers by hand.
      Additionally, the total depth of tissue necrosis surrounding incisions made with
      both lasers and contact tips is determined 48 hours postoperatively in the three
      tissues, and healing of the liver and abdominal wall muscle 21 and 35 days
      postoperatively is assessed histologically. Perioperatively determined charring,
      coagulation, and incision depth obtained in all tissues with either 805 nm or
      1,064 nm laser radiation were sensibly equivalent at equal laser power values for
      each of the two contact tip shapes tested. At equal laser power values,
      coagulation depths obtained in rabbit abdominal skin using the 300-microns
      diameter conical tip differed significantly (P < or = 0.01) from those values
      obtained with the 1,200-microns-diameter spherical tip. Incision depths obtained
      with the two different contact tip shapes at equal laser power settings in the
      different tissues studied differed in a few instances with no apparent pattern
      relating to tissue type or laser power. Depth of incisions obtained with both
      laser and tip types increases in the range of 6-12 w, but plateaus in the range
      12-18 w in the tissues studied. Incisions obtained with both diode and Nd:YAG
      laser contact were essentially hemostatic, with self-limiting oozing at
      most.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264324
TI  - Q-switched CTE:YAG (2.69 microns) laser ablation: basic investigations on soft
      (corneal) and hard (dental) tissues.
AB  - Ablative infrared lasers either show poor transmission in optical fibers (Er:YAG:
      2.94 microns; ErCr:YSGG: 2.79 microns or are characterized by potential relevant
      thermal side effects (Ho:YAG: 2.1 microns). The CTE:YAG laser (Cr,Tm, Er doted
      YAG) emits radiation at a wavelength of 2.69 microns. Efficiently high optical
      fiber transmission is accomplished (attenuation: < 8db/m for Low-Hydroxy-Fused
      Silica (LHFS): 0.3 ppm). Since the laser can easily be run in the Q-switch mode
      (pulse duration: 0.5-2.5 microseconds) thermal side effects of tissue interaction
      were expected to be low. Laser tissue interaction was studied on soft (porcine
      and human cornea), as well as on hard (human dental) tissue. Histological and
      micromorphological examinations were performed by light microscopy and scanning
      electron microscopy. It was found that ablation rates in corneal tissue increased
      from 5 to 90 microns/pulse with increasing laser fluences (5.5-20 J/cm2).
      Collateral thermal damage reached as far as 20 +/- 5 microns, and was higher (up
      to 50 microns) when craters where processed in the contact mode using LHFS
      optical fibers. In comparison to soft tissue ablation, hard dental tissue
      ablation showed very little increase of ablation rate (1-3 microns/pulse) when
      higher fluences were applied. In dental tissue processing, the ablative effect
      was accompanied by a luminescence, indicating the presence of plasma. We conclude
      that the presented CTE:YAG laser can be considered as an effective tool for a
      variety of laser surgical applications where high power optical fiber delivery is
      required and where strong thermal side effects are not desired.

PMID- 8264325
TI  - Structural changes in dentin induced by high energy, continuous wave carbon
      dioxide laser.
AB  - The effect of a continuous wave carbon dioxide laser on dentin was observed as a
      function of power density and exposure time utilizing a wet scanning electron
      microscope. Visible charring occurred for all conditions studied. Surface
      cratering and flaking were followed by melting of the dentin. Melting resulted in
      a porous layer or porous globules of resolidified material and partial sealing of
      the tubules. Beneath the melted zone is an area of altered dentin where the
      tubules appear to be filled by solidification of the melted dentin.

PMID- 8264326
TI  - Argon laser oral safety parameters for teeth.
AB  - Argon lasers have been reported to prevent or reduce demineralization of enamel
      in extracted teeth and to polymerize dental composites (using 25-100 J/cm2).
      Prior to clinical trials on caries prevention and curing composites, safety
      parameters for intraoral use of the argon laser need to be established. This
      study was conducted to determine the enamel damage, pulp temperature changes, and
      associated pulpal tissue damage following irradiation at various argon laser
      energy levels using 1.6-6.0 watts, approximately 1 and 2 mm diameter beam for 0.2
      5.0 seconds. To evaluate pulpal damage, selected dogs' teeth were irradiated in
      vivo, extracted 7 days postlasing, fixed, decalcified, sectioned, stained, and
      read for pulpal damage. Pulp temperature and enamel damage tests utilized
      extracted dog and human teeth. Temperature probes were inserted in the pulp
      chambers and temperature changes recorded as enamel surface was lased. Enamel
      surface damage was evaluated by visual and microscope examination. Results showed
      that histologic pulpal damage occurred at > 600 J/cm2. Temperature changes were <
      6 degrees F in human teeth with approximately 900 J/cm2. No enamel damage was
      observed at these energy densities. At energy densities needed for proposed uses,
      no apparent damage would be expected to pulp or enamel.

PMID- 8264327
TI  - Use of laser energy to treat central pulmonary emboli: a preliminary report.
AB  - We evaluated the ability and safety of a laser fiber placed percutaneously into a
      pig's lobar pulmonary artery to lyse pulmonary artery blood clots that were
      created in situ. We developed a model to create blood clots in situ that could be
      placed in any desired location with a radio-opaque marker at the clot position.
      An excimer laser delivered energy to a flexible 600 microns fiber in three
      experiments and a coaxial 1.6 mm multifiber catheter in the last experiment. Pre-
      and postprocedure angiograms obtained from each experiment demonstrated that
      partial laser dissolution of central pulmonary emboli in four pigs was
      accomplished successfully. To avoid perforation, it is imperative that the laser
      fiber remain coaxial during the entire lasing process. These results suggest that
      laser dissolution may become an adjunctive procedure for the treatment of central
      pulmonary emboli in those patients who cannot be treated medically.

PMID- 8264329
TI  - Optical modelling of light distributions in skin tissue following laser
      irradiation.
AB  - A Monte-Carlo method is used to compute light distributions in a multilayer skin
      model for variable width finite beams. By means of a 4-layer skin model in which
      blood may be represented as a discrete layer, vascular lesions such as port wine
      stains may be studied. Light distributions and thermal profiles are simulated,
      representing the irradiation of a port wine stain using 577 nm and 585 nm
      wavelengths. Damage thresholds at 585 nm are found to substantially exceed those
      predicted at 577 nm, although the nature of the damage differs at the two
      wavelengths. Variations due to beam width are found to be unimportant if the
      diameter exceeds 1 mm. The predictions are compared with clinical results, and a
      novel 5-layer approach based on new optical parameters is adopted to account for
      discrepancies in epidermal temperature.

PMID- 8264328
TI  - Ab-interno erbium (Er):YAG laser sclerostomy with iridotomy in Dutch cross
      rabbits.
AB  - An ab-interno technique using a pigmented rabbit model has been developed that
      uses a pulsed erbium:YAG laser to create an iridotomy with a sclerostomy through
      the same corneal incision. Laser energy was delivered with an articulated arm
      terminating in side-firing (850 or 650 microns OD) or end-firing (850 or 400
      microns OD) fiber optic endoprobes, which allowed iridotomies and sclerostomies,
      respectively, to be created. Initially, sclerostomies (8-10, 8 mJ/300
      microseconds pulses) and basal iridotomies (1-3, 4 mJ/200 microseconds pulses)
      were created with the larger probes. Problems encountered with this technique
      included corneal decompensation and rapid formation of peripheral anterior
      synechiae with occlusion of sclerostomies. The smaller endoprobes were then used
      to create mid-peripheral iridotomies and sclerostomies utilizing the same energy
      parameters. Sclerostomies created in this manner remained patent in the first
      postoperative week until the animals were sacrificed to obtain material for
      histologic study.

PMID- 8264330
TI  - Current status of infrared fiber optics for medical laser power delivery.
AB  - There are a host of fiber-optic delivery devices available for use with the
      Er:YAG, HF, CO, and CO2 lasers at 2.9, 2.8, 5.3, and 10.6 microns wavelengths,
      respectively. While many of these fibers are not as convenient to use as
      conventional silica fibers, they offer the ability to deliver infrared laser
      energy for a wide variety of medical applications. The fundamental attributes of
      fluoride glass, chalcogenide glass, single-crystal sapphire, and polycrystalline
      silver halide optical fibers are reviewed and their practical properties
      tabulated.

PMID- 8264331
TI  - Preparation of human albumin solder for laser tissue welding.
AB  - Previous studies have demonstrated that the addition of a protein solder to
      augment the laser tissue weld significantly improves postoperative results.
      Herein we describe a method for the preparation of human albumin for use as a
      laser tissue solder. We also review the brief history of laser tissue solders and
      discuss recent advances using this technology.

PMID- 8264332
TI  - Potential involvement of the transcription factor NF-kappa B in neurological
      disorders.
AB  - Reactive oxygen intermediates (ROIs) are involved in many neurological diseases.
      Despite the toxic nature of these compounds, low concentrations of ROIs can
      function as signaling molecules. One target for their signaling function is the
      inducible transcription factor NF-kappa B. Predominantly in lymphoid cells,
      induction of NF-kappa B in response to oxidative stress leads to transcriptional
      activation of many genes which are relevant for pathogen defense. These include
      the TNF, IL-6, IL-8, GM-CSF, beta-interferon, MHC class I and V-CAM genes.
      However, NF-kappa B is also abundant in various cell types of the nervous system,
      including neurons. We propose that NF-kappa B plays a role as a redox-controlled
      transcriptional activator also in cells of the nervous system and in that
      property may contribute to neurological disorders. Our finding that some neurons
      from healthy brain contain constitutively active NF-kappa B suggests a role of NF
      kappa B in normal brain function as well.

PMID- 8264333
TI  - Mechanisms and effects of lipid peroxidation.
AB  - Lipid peroxidation is an important mechanism in free radical mediated cell
      injury. It can damage cell membranes directly and the reactive carbonyl products
      may spread the damage far from the original site of radical production. It has
      long been considered to be involved in various toxic tissue injuries and in
      certain disease processes, including cancer. Paradoxically, cancer cells are very
      resistant to lipid peroxidation. Recently, it has been suggested that lipid
      peroxidation may exert more subtle effects than was previously thought possible,
      by influencing gene expression.

PMID- 8264334
TI  - Lipid peroxidation. Biopathological significance.
AB  - Peroxidation of unsaturated lipids, initially studied in the chemistry of oil and
      fat rancidity, has become a problem of increasing interest in the biological
      field, because of its proposed role in a variety of pathological conditions. The
      general mechanism of the process, the formation of toxic aldehydes capable to
      react with protein and non protein thiols, and the overall effects in cellular
      membranes are reviewed. The possible implications of lipid peroxidation as one of
      the main mechanisms of cellular damage in both toxic injury and other
      pathological conditions are discussed.

PMID- 8264335
TI  - Influence of hydroxystearic acid on in vitro cell proliferation.
AB  - Lipid peroxidation products have recently been proposed among the possible
      regulators of tumour cell growth. According to our current working hypothesis,
      the greatly diminished content of such products in tumour cells might relieve the
      inhibition of cell growth thus leading to uncontrolled proliferation. Hydroperoxy
      and hydroxy derivatives of long chain fatty acids have been identified and
      determined in normal and tumour cells. Among these, hydroxystearic acid (HSA) has
      been shown to have a different cytostatic and cytotoxic effect when administered
      to murine lung carcinoma cells or to human colon tumour cells. It interferes with
      cell cycle kinetics, blocking the murine cells in G2-M and the human ones in G0
      G1. The molecular target of HSA in both cell lines has been shown to be the cdc2
      kinase complex. The results so far obtained in tumour as long as in normal highly
      proliferating cells do not exclude a potential future use of this class of
      compounds as selective anti tumour drugs.

PMID- 8264336
TI  - Control of neoplastic cell proliferation and differentiation by restoration of 4
      hydroxynonenal physiological concentrations.
AB  - Several studies point to the existence of an inverse correlation between cellular
      lipid peroxidation and both cell proliferation and neoplastic transformation. In
      anaplastic cell lines products of membrane lipid peroxidation are very low or
      undetectable. Furthermore numerous results demonstrate effect of lipid
      peroxidation products on central biochemical pathways and intracellular
      signalling at physiological concentrations. 4-hydroxynonenal (HNE) is one of the
      most active products of lipid peroxidation. The restoration of HNE physiological
      concentrations in neoplastic cells may inhibit cell proliferation and modulate
      cell re-differentiation. This review try to summarize and critically discuss the
      effects of physiological concentrations of HNE on normal and neoplastic cell
      line.

PMID- 8264337
TI  - Vitamin E and alpha-lipoate: role in antioxidant recycling and activation of the
      NF-kappa B transcription factor.
AB  - Nuclear factor kappa B (NF-kappa B) is believed to play an important role in the
      activation of human immunodeficiency virus (HIV) which causes acquired
      immunodeficiency syndrome (AIDS). Recent findings suggesting an involvement of
      reactive oxygen species in signal transduction pathways leading to NF-kappa B
      activation have encouraged the possible clinical use of antioxidants in blocking
      HIV activation. We have examined the effects of vitamin E and alpha-lipoate
      derivatives on NF-kappa B activation, and have observed that each of these
      antioxidants behave differently. Here we propose mechanisms of antioxidant
      actions in influencing cell signalling for NF-kappa B activation.

PMID- 8264338
TI  - Effects of carotenoids on cells.
AB  - When added to cells, carotenoids display a variety of properties, including
      inhibition of mutagenesis, genotoxicity, malignant transformation, and growth of
      tumor cells. In addition, carotenoids increase cell-cell communication, and may
      have direct effects as cellular antioxidants.

PMID- 8264339
TI  - n-3 PUFA and alpha-tocopherol control of tumor cell proliferation.
AB  - Subjects at high risk for colon cancer received different doses of fish oil on a
      30-day randomized double-blind trial to evaluate the chemopreventive effect of n
      3 fatty acids against colorectal cancer. Using rectal mucosal proliferation,
      assessed with 3H-thymidine autoradiography, fish oil induced in the treated
      groups but not in the placebo group a change in the proliferative pattern, which
      resulted similar to that observed in low risk population; in the same groups
      rectal mucosal n-3 fatty acid content increased, where arachidonic acid level
      decreased. Moreover, n-3 PUFA treatment induced modifications of Vitamin E
      status. The results suggest that n-3 PUFA could protect high-risk subjects from
      colon cancer by a mechanism involving a modulation of Vitamin E.

PMID- 8264340
TI  - Defective gene expression of MnSOD in cancer cells.
AB  - Reactive oxygen species (ROS) have been frequently implicated in the initiation
      and promotion phases of carcinogenesis. Antioxidant enzymes, which can antagonize
      this process, are lowered in a number of malignancies. The enzyme most commonly
      decreased is the mitochondrial Mn-containing superoxide dismutase (MnSOD) encoded
      by a nuclear gene mapped on the band 6q21, a region frequently deleted in several
      human tumours. The close association of del(6q) with diminution of MnSOD has led
      to suggest that MnSOD might be a new type of tumour-suppressor gene. This
      hypothesis is also sustained by the finding that transfection of MnSOD cDNA into
      human melanoma cell lines suppress the malignant phenotype. There are, however,
      conflicting observations that tend to ascribe the deficiency of the MnSOD
      activity more to a defect in the expression of the gene than to its deletion. In
      many transformed cell lines, including some with marked del(6q), there is no
      change in the dosage of the MnSOD gene and the enzyme is highly inducible by
      various pro-oxidant agents. Transition metals (Mn, Fe) have been found to be
      highly deficient in human and rodent tumours. Owing to the second messenger
      function of ROS in activating transcription factors (NF-kB, AP-1) and to the
      ability of Mn to facilitate the dismutation of O2- to H2O2 and of Fe to
      participate in the Fenton reaction, we propose that in the early stage of
      carcinogenesis an impairment of the signal transduction machinery, related to the
      metal deficiency, might limit the binding to DNA of transcription factors and
      cause the defect in the MnSOD gene expression.

PMID- 8264341
TI  - Modulation of hepatic fibrogenesis by antioxidants.
AB  - The oxidative damage of liver tissue appears to favour a fibrogenic process,
      through the stimulation of TGF beta 1 and procollagen gene expression. The latter
      effect has been also showed by a well defined end-product of lipid peroxidation,
      4-hydroxy-2,3-nonenal in human Ito cell culture. "In vivo" and "in vitro" data
      give evidence of a strong down modulation of TGF beta 1 and collagen expression
      afforded by supplementation with different antioxidant molecules.

PMID- 8264342
TI  - d-alpha-tocopherol control of cell proliferation.
AB  - Uncontrolled cell growth is at the basis of neoplastic proliferation and
      arteriosclerotic lesions. In vitro proliferation of vascular smooth muscle cells,
      Balb c/3T3 fibroblasts, retinal neuroepithelial cells and neuroblastoma cells is
      inhibited by d-alpha-tocopherol. On the contrary Chinese hamster ovary cells,
      osteosarcoma cells and macrophages are not sensitive. PDGF-BB activated
      proliferation is highly d-alpha-tocopherol sensitive while lysophosphatidic acid
      induced growth is poorly inhibited. d-beta-Tocopherol, an analogue of d-alpha
      tocopherol, with similar antioxidant properties, does not inhibit proliferation.
      Protein kinase C activity is inhibited by d-alpha-tocopherol but not by d-beta
      tocopherol, suggesting a central role of this enzyme in the control of cell
      proliferation by d-alpha-tocopherol. Activation of the transcription activation
      complex AP-1 (but not NFKB) is prevented by d-alpha-tocopherol and not by d-beta
      tocopherol.

PMID- 8264343
TI  - Action of lipid peroxidation products on phosphoinositide specific phospholipase
      C.
AB  - 4-Hydroxynonenal (HNE), a major lipid peroxidation product, displays several
      biological actions. Among them, the differentiation of human HL-60 cells and the
      stimulation of neutrophil oriented migration occur at concentrations which can be
      actually found in normal tissues and in body fluids. In spite of its chemotactic
      activity, HNE fails to increase neutrophil oxidative metabolism. The action of
      the aldehyde on cell migration appears to be mediated by a phosphoinositide
      specific phospholipase C. The acceleration of phosphatidylinositol turnover
      induced by 10 pM 4-hydroxyoctenal, another lipid peroxidation product, is
      prevented by the pretreatment of neutrophils with pertussis toxin. The mechanism
      of action of these 4-hydroxyalkenals appears to follow pathways common to other
      chemoattractants, but some differences can be found too. In particular HNE seems
      unable to stimulate phospholipase D activity. The action of 4-hydroxyalkenals and
      other lipid peroxidation products on transmembrane signalling systems and on
      phospholipid metabolism might regulate several cell functions, such as motility,
      proliferation and differentiation.

PMID- 8264344
TI  - Ifosfamide induced stress response in human lymphocytes.
AB  - Ifosfamide, an isomer of cyclophosphamide, has been shown to be one of the most
      effective antineoplastic agents for the treatment of human malignancies. There is
      considerable evidence that the intracellular status of glutathione (GSH) plays a
      major role in modifying the cytotoxicity of ifosfamide in cells and tissues. We
      have studied the effects of 4-hydroperoxy-ifosfamide (4-OOH-IF) upon the
      proliferation of human peripheral blood lymphocytes (PBL) and the intracellular
      GSH content. The major finding was that occurrence of significant inhibition of
      [3H]-thymidine incorporation in interleukin-2 (IL-2) expanded PBL after exposure
      with 4-OOH-IF was accompanied by substantial depletion of intracellular GSH
      content in these cells. PBL seemed to be more sensitive to this drug induced
      effect comparing our results obtained in other cells (e.g. Ewing sarcoma, Chinese
      hamster ovary). In PBL 4-OOH-IF also induced rapid phosphorylation of the small
      heat shock protein (HSP27) signaling a similar type of stress response as
      reported for several other agents (e.g. arsenite, phorbol ester, tumor necrosis
      factor). Reconstitution of the depleted GSH content in PBL after treatment with 4
      OOH-IF could be achieved by GSH-monoethylester and mesna within 24 hours of
      postincubation time. From these results we conclude that human lymphocytes are
      sensitive targets for ifosfamide induced metabolic stress during treatment. This
      might have further importance in regard to the immunological function of these
      cells.

PMID- 8264345
TI  - We're wonderfully creative. Let's take the next step!

PMID- 8264346
TI  - A synthetic alternative.

PMID- 8264347
TI  - Collaboration between education and service. Results in a new patient program.

PMID- 8264348
TI  - Quality improvement in patient education.

PMID- 8264349
TI  - Kangaroo care: skin-to-skin contact in the NICU.

PMID- 8264350
TI  - Women with spinal cord injuries require sensitive reproductive care.

PMID- 8264351
TI  - Why parents use the warm line.

PMID- 8264352
TI  - Six myths of maternal posture during labor.

PMID- 8264353
TI  - Another way to administer antiepileptic medications in infants and children.

PMID- 8264354
TI  - Sleep position of infants: applying research to practice.

PMID- 8264356
TI  - Time series analysis. Part II: Forecasting.

PMID- 8264357
TI  - Lead poisoning.

PMID- 8264355
TI  - Stopping the spread of disease while protecting individual rights.

PMID- 8264358
TI  - Whither criminal justice?--the report of the Royal Commission on criminal
      justice.

PMID- 8264359
TI  - Retracted confessions: through opiate withdrawal to a new conceptual framework.
AB  - We note growing concern by defence councils over the reliability of confessions
      obtained from suspects withdrawing from opiate dependence. We focus on a case
      report and highlight the conceptual weaknesses of current thinking about
      confessions. A philosophical model is adapted to clarify the theoretical aspects
      and thereby provide a conceptual framework to help the doctor confronted with the
      practical issue of how to assess a suspect's fitness for interrogation or the
      reliability of an individual's confession. We argue that the practice of not
      treating withdrawal in custody is unjust and inhumane. The model presented is of
      value in dealing with the issues raised by retracted confessions generally and
      not just in the specific instances where the suspect is a drug user.

PMID- 8264360
TI  - The diagnosis of drowning by quantitative and qualitative diatom analysis.
AB  - The reliability and applicability of quantitative and qualitative diatom analysis
      in the diagnosis of drowning has been evaluated. Water and organ samples of
      immersion cases reported in the area covered by the Department of Forensic
      Medicine of the London Hospital Medical College, were analysed using both light
      and scanning electron microscopy. Controls included organ samples of the bodies
      of people who died from natural causes and exclusion of contamination. Organ
      samples of both immersion and control cases were prepared by chemical digestion
      with concentrated nitric acid. Diatoms were present in the majority of samples of
      organs of both immersion and control cases but there was a significant
      quantitative difference between the number of diatoms in control and immersion
      cases. Qualitative analysis of water and organ samples of immersion cases
      supported the diagnosis of death due to aspiration of water in approximately a
      third of the total of bodies found in water. It has been suggested that the
      present analysis can be used as basic criteria for standardization of the diatom
      method.

PMID- 8264361
TI  - Assault behaviour in acute psychiatric wards and its relationship to violence in
      the community: a comparison of two health districts.
AB  - Evidence suggests that the level of violence in psychiatric institutions reflects
      that of society at large. This study investigates this by comparing the
      psychiatric hospital assault rates and the violent crime rates of two District
      Health Authorities. The differences between the two districts on each of these
      parameters were found to be of a very similar order, which would tend to support
      the hypothesis.

PMID- 8264363
TI  - The baby mix-up in the maternity unit.

PMID- 8264362
TI  - The legal liability of the nurse--the lawyer's view.

PMID- 8264364
TI  - Study into the ability of healthy people of small stature to satisfy the sampling
      requirements of breath alcohol testing instruments.
AB  - In a previous study (Gomm et al., 1991) people with a variety of respiratory
      diseases were tested and criteria defined for assessing their ability to provide
      samples for Breath Alcohol Testing Instruments. This study investigated the
      possible problems which may be encountered by healthy people of small stature-
      5ft 5in (166cm) or less--who do not suffer from a respiratory disease. This study
      followed the same pattern as the earlier work in that lung function (Forced
      Expiration Volume in One Second (FEV1) and Forced Vital Capacity (FVC)) was
      measured by spirometry, and Peak Expiration Flow Rate (PEFR) was measured using a
      Wright peak flow meter. Following the lung function measurements the subjects
      were requested to provide samples for Breath Alcohol Testing Instruments used by
      the Police in Great Britain. As with the previously reported work (Gomm et al.,
      1991), this study found that the FEV1 and FVC gave the most reliable indication
      of a person's capability of satisfying the sampling requirements of Breath
      Alcohol Testing Instruments, but on this occasion the PEFR also provided a good
      confirmatory indication. Because there were no subjects with interstitial lung
      diseases the values determined by this study on 48 healthy adults indicate that a
      healthy person of small stature should be capable of supplying a suitable breath
      sample if their FEV1, FVC and PEFR are greater than 2.31, 2.61 and 330 l/min
      respectively.

PMID- 8264365
TI  - An objective study of two medicolegal Systems--Libyan and British.
AB  - This work presents important information about the medicolegal systems in two
      different countries through the author's personal experience during his work. In
      Libya, the Medicolegal Centres, attached to the Justice Department, receives all
      cases referred by the Director of Public Prosecution or by the Judge. These
      constitute a wide range of cases which include in descending order of frequency,
      age estimation, injuries, autopsies, sexual offences, criminal responsibility,
      medical mishaps, disputed paternity and nullity of marriage. In Scotland, the
      Department of Forensic Medicine and Science at the University of Glasgow receive
      only a proportion of the total number of cases investigated by the Procurator
      Fiscal in Glasgow. These are exclusively deaths that require medicolegal
      autopsies, which average 458 per year. The medicolegal Centre in Benghazi
      receives all referrals from the courts, which average 1780 cases per year, but
      autopsies constitute only 14.4% (256 cases per year). A total of 1144 autopsies
      performed in Glasgow during a period of 2.5 years, and 7121 medicolegal cases
      investigated in Benghazi during a period of 4 years (1022 of that were
      autopsies), are presented in 12 tables and duly discussed. The outstanding
      observation is the marked male preponderance in deaths from unnatural causes in
      Benghazi, (80% of the total), compared to less marked male preponderance in
      Glasgow, (60% of the total). This is explained by the fact that due to social
      custom in Libya, females have limited outdoor activities and lead a rather
      domestic life compared to females in Britain.

PMID- 8264366
TI  - Matricide: the schizophrenic crime?
AB  - The aim of the study was to further examine the view that matricide is 'the
      schizophrenic crime' (Gilles, 1965). This report represents a comprehensive,
      retrospective and national study of all individuals in Scotland who, between 1957
      and 1987 inclusive, were charged with the murder or the culpable homicide of
      their biological mother. Files of High Court indictments were examined for the
      relevant years to identify offenders prior to disposal, and individuals were
      followed up with respect to diagnosis and disposal. Twenty-six (twenty-three men
      and three women) were convicted of the murder or culpable homicide of their
      biological mother. Only 50 per cent (thirteen subjects) were known to the State
      Hospital, Carstairs. Six (24 per cent) subjects suffered from schizophrenia,
      seven (24 per cent) were given no diagnosis, five (20 per cent) suffered from
      personality disorder, four (16 per cent) from the alcohol dependence syndrome,
      three (12 per cent) from depressive illness, and one (4 per cent) from hypomania.
      Thus, whilst schizophrenia is over-represented in this subgroup of offenders,
      matricide should not be viewed as the schizophrenic crime. Given the prevalence
      of mental disorder in this group, pre-trial assessment by a Forensic Psychiatrist
      should be mandatory.

PMID- 8264367
TI  - Infanticide in England and Wales.
AB  - In England and Wales children under one year of age are at four times greater
      risk of becoming victims of homicide than either older children or the general
      population. The annual rate of infant homicide (45 per million) has remained
      relatively constant since the Homicide Act (1957) in contrast with a progressive
      fall in the infant mortality rate. Details from Home Office records of all
      infants under a year who were the victims of homicide during 1982-1988 are
      presented. Infants were most at risk on the first day of life--neonates accounted
      for 21% of victims and 13% of the victims were between one day and one month old.
      Thereafter the proportion decreased steadily so that by the final quarter of the
      first year the risk of becoming a homicide victim equalled that of the general
      population. Excluding neonates, there were more male victims than female ones,
      especially in the first three months. A parent was the most likely perpetrator.
      For all neonaticides the mother was recorded as a suspect, 36% of these mothers
      were subsequently indicted, all but two were convicted of infanticide and all
      their convictions resulted in probation. For children over a day marginally more
      fathers than mothers were recorded as the prime suspect. Mother and father
      suspects were equally likely to be indicted and also equally likely to be
      convicted of a homicide offence. However, mothers received both less severe
      convictions and less severe sentences than fathers. Fathers were more likely than
      mothers to have killed their infants using violence which wounded. Nonetheless
      sentences were unrelated to the brutality of the offence: mothers who had killed
      with wounding violence received less severe penalties than fathers who had killed
      in a non-wounding way.

PMID- 8264368
TI  - Fatal agricultural accidents.
AB  - During the period 1969-1988, 33 victims (30 males and 3 females) of agricultural
      accidents were autopsied at the University Institute of Forensic Medicine in
      Copenhagen. Five were under the age of 15 years. The median age was 51 years. The
      most frequent types of accident were machinery accidents (45%), falling from a
      height (30%) and suffocation, including drowning, (12%). The place of the
      accident was meadow/field (36%), stable/barn (24%), farmyard (24%) and public
      road (12%). Severe lesions in all body regions dominated the picture with a
      preponderance of skull/brain and chest lesions. Skull/brain lesions were found in
      80% of the cases of falling from a height, while 87% of the machinery accident
      cases had severe chest lesions. More effective control of machinery and a data
      collection system for these accidents are proposed.

PMID- 8264369
TI  - Cave vulgantem morbum--tuberculosis.
AB  - This study investigates the circumstances surrounding all cases of tuberculosis
      found at autopsy in Auckland during the period 1975-1992. Cases were placed in
      one of six categories according to the medical history and autopsy findings. Of
      the 34 cases in the study 22 were clinically undiagnosed prior to autopsy. Of
      these, six exhibited respiratory symptoms that should have led to a diagnosis and
      three reported unexplained chronic symptoms such as weight loss for which
      tuberculosis should at least have been considered. Only 10 cases were correctly
      diagnosed before death. The autopsy plays an important role in finding
      undiagnosed cases of tuberculosis, as patient contacts may then be followed up.
      The vital role of post-mortem examination in medical audit and public health is,
      once again, demonstrated.

PMID- 8264370
TI  - A bolt from the blue.
AB  - The crossbow was one of the most efficient military weapons of the Middle Ages
      but the development of portable firearms meant that it was eventually relegated
      to the museum shelf. The medieval crossbow was accurate and deadly but took some
      time to load because of the windlass used to wind the string, thus increasing the
      velocity and range of the bolt, or quarrel. By contrast, the English longbows of
      Crecy and Agincourt were far less accurate but could fire six arrows in the time
      taken to shoot one bolt and the continual raining-down of missiles proved more
      successful in battle than accuracy of aim. This paper describes the homicide of a
      young business woman outside her London flat in 1987. Today crossbow fatalities
      are extremely rare on both sides of the Atlantic but Dr Siva described a case of
      suicide in 1979 and Professor Gresham presented a case of crossbow homicide to
      the BAFM in June 1976.

PMID- 8264371
TI  - Triplets where monozygotic siblings are concordant for arson.
AB  - Triplets are described where the two genetically identical brothers are arsonists
      and both have sociopathic personality disorder rated using the Personality
      Assessment Schedule. The third, non-identical brother has not committed arson and
      does not have a personality disorder.

PMID- 8264372
TI  - Wilson's disease and offending behaviour--a case report.

PMID- 8264373
TI  - The enemy within.

PMID- 8264374
TI  - Microsurgical neurolysis: its anatomical and physiological basis and its
      classification.
AB  - Neurolysis is a procedure which has to be performed if the gliding apparatus of a
      peripheral nerve does not function, and consequently, adhesions and fibrosis
      develop. The gliding tissue has to provide the ability for the nerve to adapt to
      the different position of the extremity by longitudinal passive movement. The
      paraneurium provides movements between the nerve and the surrounding tissue; the
      interfascicular epineurium provides the possibility of the movement within the
      nerve. Internal neurolysis is defined as surgery within the nerve if the
      epifascicular epineurium is completely transected. A classification of different
      degrees of fibrosis is given with special reference to the procedure which has to
      be done in each case. Neurolysis is a step-wise procedure with the aim to
      decompress the fascicles and which is immediately stopped if this aim is
      achieved. In very severe cases, if the gliding tissue does not regenerate, a
      gliding tissue flap to envelope the nerve may solve the problem.

PMID- 8264375
TI  - Enzymhistochemical evaluation of ulnar nerve grafts in brachial plexus lesions.
AB  - Our concept for the reconstruction of brachial plexus injuries includes an
      intercostal nerve transfer to the vascularized ulnar nerve graft. A free
      neurovascular latissimus dorsi is then transferred in a second stage operation.
      For optimization of the regeneration result, the operative planning of the second
      step includes nerve biopsies and enzymhistochemical evaluation for the
      distribution of motor axons. The staining method according to Scabolcz et al. is
      described and clinical cases are presented.

PMID- 8264376
TI  - Arteriovenous fistula with a saphenous long loop.
AB  - After radiation, chronic infection or previous operations recipient vessels for
      free tissue transfer become difficult to find. It may be necessary to locate
      vessels remote from the area of reconstruction and to construct long venous
      grafts. Long venous grafts can be compressed in the tissue tunnels that may be
      required. In this series of patients, an arteriovenous fistula was created with a
      long saphenous loop 10 to 21 days prior to tissue transfer. The saphenous loops
      were placed close to the area for reconstruction and when divided at the time of
      transplantation, provided one artery and one vein. In this series of 12 cases,
      adequate vascularization was achieved in 10 cases. In the other 2 cases, we
      believe that maturation of the fistula may have been necessary before proper
      function. The other advantages of the technique are: the procedure can be carried
      out under local anaesthesia, ease of positioning of the patient on the operating
      table, and a reduction in the time taken to perform the tissue transfer.

PMID- 8264377
TI  - Primary shortening with secondary limb lengthening in severe injuries of the
      lower leg: a six year experience.
AB  - Multiple secondary grafting procedures may be necessary in cases of complete or
      partial amputation of the lower limb if the aim is to preserve the initial limb
      length. The traditional concept of staged reconstruction often leads to a
      prolonged hospitalisation and a high complication rate, especially in cases with
      segmental nerve defects of more than one major nerve and severe skin loss. To
      minimize multiple secondary operations of soft tissue and bone, we have developed
      the concept of primary shortening with secondary limb lengthening. We perform a
      primary shortening of the amputation stump and the severed limb at the time of
      replantation, in order minimize the skin defect and to undertake a primary wound
      closure and/or primary nerve suture. Six to 12 months after replantation,
      secondary limb lengthening is started, using an external or internal distraction
      device. Since 1985, 7 patients presenting with complete or partial amputation of
      the lower leg had been treated using this concept. The indications, operative
      technique, complications and results are shown and discussed, comparing this new
      concept to the traditional concept with extensive free soft tissue transfer and
      secondary nerve grafting.

PMID- 8264378
TI  - Replantation of the thumb: survival rate and functional recovery in correlation
      with type of injury.
AB  - During a period of 4 years, we attempted replantation of an amputated thumb in 21
      patients. We present the survival rate as well as the functional recovery in
      correlation with type of injury. In 21 thumbs, 16 survived surgery (76.2%); 2 out
      of 5 losses belonged to the guillotine category and 3 belonged to the crush
      avulsion category. Out of the 11 thumbs that belonged to the crush-avulsion type,
      8 survived, which is a 72.7% success rate. Eight out of 10 thumbs of the
      guillotine type survived, an 80% success rate. The cosmetic and functional result
      was satisfactory.

PMID- 8264379
TI  - Preservation of peripheral nerve grafts with Schwann cell culture medium.
AB  - Preservation of peripheral nerves may, in the near future, play an important role
      in reconstructive surgery, especially if recent advances in immunosuppressive
      therapy are taken into account. Therefore, it has to be investigated whether
      peripheral nerves can be stored for some time after harvesting without
      diminishing their regenerative potential. Previous experiments of our group could
      demonstrate only little benefit of organ storage solution (HTK) or normal saline
      (NaCl 0.9%) to peripheral nerves when kept at cold ischaemia of 4 degrees C for
      32 and 72 hours. In this presentation, we are reporting the results of peripheral
      nerve storage in Dulbecco's Modified Eagle Medium which has been used for Schwann
      cell culture. In 30 adult Sprague-Dawley rats, a 2.5 cm segment of the right
      sciatic nerve was harvested and kept at 4 degrees C for 14, 32, 72, and 120
      hours. It was then reimplanted into the donor animal; regeneration quality was
      assessed clinically, histologically and morphometrically after 6 weeks. Best
      regeneration results were obtained in the 32 and 72 hour groups; regeneration
      here was comparable to the normal controls. These results are explained with the
      positive effect of nerve predegeneration.

PMID- 8264380
TI  - Preventive haemostasis with an inflatable tourniquet for microsurgical distal
      arteriovenous fistulas for haemodialysis.
AB  - The creation of a distal arteriovenous fistula for haemodialysis is made easier
      by using preventive haemostasis with an inflatable tourniquet. Preventive
      haemostasis reduces the duration of the surgery and reduces the arterial spasm
      provoked by the dissection. When microsurgical techniques and preventive
      haemostasis are used, it is possible to create fistulas even in very small
      children.

PMID- 8264381
TI  - Correction of hypoplastic thumb by free transfer of metatarsal bone: a case
      report.
AB  - A new form of correction of hypoplasia of the thumb is presented in a case of
      grade 3 thumb hypoplasia. The distal half of the second metatarsal together with
      its epiphyseal plate was used to lengthen the first metacarpal bone and improve
      thumb function. This method represents a promising alternative to pollicization
      in this type of thumb hypoplasia.

PMID- 8264382
TI  - Two-dimensional protein electrophoresis in phylogenetic studies.

PMID- 8264383
TI  - Ancient proteins in fossil bones.

PMID- 8264384
TI  - Comparative immunological methods.

PMID- 8264385
TI  - Information content of immunological distances.

PMID- 8264386
TI  - Isolation of DNA from eukaryotic algae.

PMID- 8264387
TI  - Comparative studies of genome content.

PMID- 8264388
TI  - Evolutionary analyses of repetitive DNA sequences.

PMID- 8264389
TI  - Collection and storage of land plant samples for macromolecular comparisons.

PMID- 8264390
TI  - DNA-DNA hybridization of single-copy DNA sequences.

PMID- 8264391
TI  - Comparative studies of gene copy number.

PMID- 8264392
TI  - Optimal preparative methods for producing comparative gene libraries.

PMID- 8264394
TI  - Use of randomly amplified polymorphic DNA markers in comparative genome studies.

PMID- 8264393
TI  - Surveying plant genomes for variable number of tandem repeat loci.

PMID- 8264395
TI  - Equipping and organizing comparative molecular genetics laboratories.

PMID- 8264396
TI  - Detection and characterization of transposable elements.

PMID- 8264397
TI  - DNA-DNA hybridization approaches to species identification in small genome
      organisms.

PMID- 8264398
TI  - In vivo analysis of plant 18 S ribosomal RNA structure.

PMID- 8264399
TI  - Sequencing of polymerase chain reaction-amplified DNAs.

PMID- 8264400
TI  - Rapid production of single-stranded sequencing template from amplified DNA using
      magnetic beads.

PMID- 8264401
TI  - DNA sequences from old tissue remains.

PMID- 8264402
TI  - Analysis of DNA sequence variation at population level by polymerase chain
      reaction and denaturing gradient gel electrophoresis.

PMID- 8264403
TI  - Detection of variability in natural populations of viruses by polymerase chain
      reaction.

PMID- 8264404
TI  - Phylogenetic analysis of restriction site data.

PMID- 8264405
TI  - Site-directed mutagenesis in analysis of protein-protein interactions.

PMID- 8264406
TI  - Collection and storage of invertebrate samples.
AB  - The validity of any comparative study is dependent on the reliability of the
      identification of the samples in the study. Not all researchers are experts in
      the field of identification of samples, nor do all researchers have quick and
      ready access to expert systematists who can accomplish the task of
      identification. The importance of verification of sample identity for comparative
      studies is vital. We describe several methods by which researchers can obtain and
      identify samples from the wild, and we suggest methods by which voucher samples
      can be obtained for future reference to these collected samples. We outline
      alternatives to collection of samples from the wild, such as purchase from stock
      centers and biological supply companies. Museum collections can also be extremely
      helpful in obtaining complete organismal samples for comparative studies.

PMID- 8264407
TI  - Comparative studies of mammalian Y chromosome.

PMID- 8264408
TI  - Detection and quantification of concerted evolution and molecular drive.

PMID- 8264409
TI  - Assaying differential ribosomal RNA gene expression with allele-specific probes.

PMID- 8264410
TI  - Assays for copy number, differential expression, and recombination in lysozyme
      multigene family.

PMID- 8264411
TI  - Identification of lens crystallins: a model system for gene recruitment.

PMID- 8264412
TI  - Reconstruction and testing of ancestral proteins.

PMID- 8264413
TI  - Comparative method in study of protein structure and function: enzyme specificity
      as an example.

PMID- 8264414
TI  - Acquisition of new metabolic activities by microbial populations.

PMID- 8264415
TI  - Chemostats used for studying natural selection and adaptive evolution.

PMID- 8264416
TI  - Experimental determination of rates of concerted evolution.

PMID- 8264417
TI  - Collection and storage of fungal and algal samples.

PMID- 8264418
TI  - One-dimensional electrophoretic comparisons of plant proteins.

PMID- 8264419
TI  - Starch gel electrophoresis in vertebrates.

PMID- 8264420
TI  - Cytomegalovirus IgM antibody detection: comparison of five assays.
AB  - Human Cytomegalovirus (CMV) infection can result in a dramatic disease in
      immunosuppressed patients. For effective treatment sensitive and specific
      procedures are required for prompt and early diagnosis of active CMV infection.
      In the present study five different serological assays were used for detection of
      CMV-specific immunoglobulin M antibodies (IgM) in 78 sera, obtained from patients
      with a clinical suspicion of CMV infection. In addition, sequential sera,
      obtained from renal transplant recipients who experienced a primary CMV
      infection, were analysed by the five IgM detection assays. The assays used were
      two enzyme-linked immunosorbent assays (ELISA): the Vironostika CMV ELISA from
      Organon Teknika (ELISA-1) and the Monosan CMV ELISA from Sanbio (ELISA-2), the
      CMV microparticle enzyme immunoassay (MEIA) from Abbott and two Western
      (immuno)blotting techniques using purified CMV structural viral proteins of the
      AD169 strain (IB-AD169) and the major non structural DNA binding protein of 52
      kiloDalton (IB-Rp52) as antigenic material. The results of the assays were
      compared to each other with respect to sensitivity, specificity and overall
      agreement, as well as incidence of false positive and false negative results.
      Although the MEIA gave the highest sensitivity, the ELISA-1 combined a high
      sensitivity with a high specificity and therefore appears the most suitable
      method for determination of active CMV infection.

PMID- 8264421
TI  - Production and release of tumor necrosis factor alfa, interleukin-1B and
      interleukin-6 by human mononuclear leukocytes stimulated with pertussis toxin.
AB  - Pertussis toxin (PT) has been previously shown to affect a wide variety of immune
      responses and to cause lymphocyte proliferation. In this study, we examined the
      effect of PT on cultured human peripheral blood lymphocytes and monocytes with
      the regard to the capability of this toxin to stimulate the production and
      release of various cytokines. PT was found to induce the production and release
      of Tumor Necrosis Factor alfa (TNF-alfa) and Interleukin-6 (IL-6) by both human
      lymphocytes and monocytes and IL-1 (IL-1B) beta by human monocytes in culture.
      Most activities of PT in vitro were achieved at the optimal concentration range
      of 1-0.01 microgram/ml, which is responsible for the adjuvant effect of PT in
      vivo. Since TNF-alfa, IL-1 beta and IL-6 are potent mediators of inflammation,
      the production and release of these cytokines by PT and Bordetella pertussis
      itself may play an important role in antibacterial defenses against such
      infection.

PMID- 8264422
TI  - Identification of Leptospira interrogans strains by monoclonal antibodies and
      genomic analysis.
AB  - A recombinant probe derived from a genomic library of serovar hardjo strain
      Hardjoprajitno, and a panel of serovar specific Monoclonal Antibodies (MAbs) were
      used for the characterization of 31 Leptospira isolates from cattle and swine.
      The two methods performed equally well in serovar identification except for the
      distinction of the genotypes hardjoprajitno and hardjobovis within serovar hardjo
      which could only be obtained by genomic analysis. The combination of
      immunological and genetic information was also useful to evaluate the degree of
      variability of Leptospira strains. The quality of the patterns and the
      sensitivity provided by a digoxigenin labelled probe were comparable to those
      obtained with a radioactive reagent.

PMID- 8264423
TI  - Characterization of mesophilic Aeromonas from clinical specimens by computerized
      analysis of SDS-PAGE protein profiles and by enzymatic activity.
AB  - Mesophilic Aeromonas (Aeromonas hydrophila, Aeromonas sobria, Aeromonas caviae)
      have recently been considered important aetiological agents of human diseases,
      mainly gastrointestinal infections. Although several findings have pointed out
      the significance of this group of microorganisms as enteric pathogens and
      suggested the presence of virulence factors, epidemiological and clinical studies
      are limited by the difficulty of correctly identifying mesophilic Aeromonas at
      the species level. SDS-PAGE of radiolabelled total protein profiles and bacterial
      enzymatic activities were used to type 31 clinical isolates (6 A. hydrophila, 7
      A. sobria and 18 A. caviae) from patients with gastroenteritis and from healthy
      controls. Analysis of SDS-PAGE protein patterns, reinforced by the UPGMA-grouping
      system (AMBIS software) provided a good characterization of A. caviae strains as
      a homogeneous group of microorganisms, possessing significant differences from
      the other two species of mesophilic Aeromonas, in good agreement with biochemical
      and enzymatic tests. Data obtained in analyzing A. sobria protein profiles
      clearly showed two groups, with a correlation coefficient (CC) = 0.70, which in
      our experience is a doubtful value for assigning two strains to the same species.
      Strains biochemically identified as A. hydrophila showed a CC = 0.64, which is
      equally not acceptable for species assignment. Inter-species comparison
      highlighted this heterogeneity, showing two mixed subgroups, both containing
      strains that were assigned to A. sobria and A. hydrophila species on the basis of
      biochemical features.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264424
TI  - Plasmid loss from gram-negative bacteria exposed to subinhibitory concentrations
      of beta-lactam drugs and azithromycin.
AB  - The stability of F'lac, pW101 and pHSG298 in Escherichia coli K12 exposed to
      subinhibitory concentrations of beta-lactam antibiotics, amikacin and
      tetracycline was studied. High molecular weight low copy plasmids (F'lac and
      pW101) were eliminated from bacteria treated with PBP-3 binding molecules, while
      a low molecular weight high copy extrachromosomal element (pHSG298) was not. None
      of the carbapenem antibiotics, mecillinam, amikacin or tetracycline promoted high
      rate plasmid loss from their hosts. Under the same conditions, plasmid-mediated
      ampicillin-resistance due to beta-lactamase production was also lost from
      F'lacTn1-carrying bacteria. In contrast, the high copy R6K plasmid was stably
      inherited in their hosts with the exception of those organisms treated with
      cefixime. When the same experiments were performed with a Klebsiella pneumoniae
      strain induced to form filaments by azithromycin at sub-MICs, F'lacTn1 and pW101
      loss was detected, while pHSG298 was stably inherited. These results confirm
      previous observations that plasmid stability is correlated with cell shape and
      that recovery is more easily achieved when bacteria undergo an unbalanced
      division resulting in cell filamentation.

PMID- 8264425
TI  - Enterococci and staphylococci isolates from rumen of fallow deers and their
      antimicrobial activity.
AB  - This work presents enterococci and staphylococci isolated from the rumen content
      of fallow deers, their characteristics and antimicrobial activity. On the basis
      of biochemical tests, strains isolated were allotted to the species Enterococcus
      solitarius, E. malodoratus, Staphylococcus warneri, S. aureus, S. sciuri subsp.
      sciuri and S. xylosus. All strains produce lactic acid in the range from 0.303 to
      0.500 mol.l-1. Isolated strains were found to be resistant or sensitive to the
      antimicrobial additives screened. Most isolates showed antimicrobial activity
      against both Gram-positive and Gram-negative test organisms reaching clear zones
      of inhibition (diam. 2-5 mm) with bacteriocidic effect.

PMID- 8264426
TI  - Enhancement of the antitrichomonal activity of 5-nitroimidazole derivatives by
      hydrogen peroxide.
AB  - The in vitro sensitivity of nine Trichomonas vaginalis isolates to commonly
      employed 5-nitroimidazoles (metronidazole, nimorazole, ornidazole and tinidazole)
      was evaluated in absence and in presence of sub-inhibitory concentrations of
      hydrogen peroxide (H2O2). Co-incubation with H2O2 and 5-nitroimidazole compounds
      decreased the MIC values of the strains exhibiting cross-resistance to these
      drugs. It was suggested that H2O2 produced in the inflammatory process during
      trichomonal infection could enhance the therapeutic effect of 5-nitroimidazole
      drugs.

PMID- 8264427
TI  - Natural infection of dogs by influenza C virus: a serological survey in Spain.
AB  - Two seroepidemiological surveys carried out so far, one in Japan, the other in
      France, gave a strong indication that dogs may be naturally infected by influenza
      C virus, considered to be exclusively human until recently. In this work, 101
      serum samples were collected during winter 1989/1990 from dogs in Castilla y
      Leon, Spain. Sera were tested for the presence of antibodies to influenza C virus
      by Hemagglutination Inhibition (HI) test. Using antibody absorption by
      staphylococcal protein A, we demonstrated the specificity of the results.
      Significant HI activity was found in 56.3% of the 101 tested sera and titres
      ranged from 25 to 200.

PMID- 8264428
TI  - Established thyroid cell line of newborn pig (NPTh).
AB  - A newly established cell strain capable of continuous cultivation derived from
      newborn pig thyroid (NPTh), is discussed. The karyotype study revealed that the
      cell line has a heteroploid chromosome pattern, but the altered karyotype did not
      seem to be related to malignancy. It is suggested that the cells may be useful
      for investigations connected with the porcine viruses.

PMID- 8264429
TI  - Cell wall-active antibiotics induce specific alterations of the electrophoretic
      profile of membrane proteins in a Staphylococcus aureus strain.
AB  - The effect of six representative cell wall-active antibiotics upon the membrane
      proteins of Staphylococcus aureus CIP 65-25 was studied. The profiles of whole
      membrane proteins and of penicillin-binding proteins of strain CIP 65-25 grown on
      an antibiotic-free medium were analysed and compared with those of nine other S.
      aureus strains. Both profiles were found to be very similar for all strains
      examined. Cell wall-active antibiotics brought about definite changes dealing
      with a few membrane proteins of strain CIP 65-25. Some polypeptide bands of the
      control profiles decreased or vanished after exposure to antibiotics whereas
      others rose only in antibiotic-treated bacteria. None of these modified
      polypeptides was a penicillin-binding protein. Their possible involvement in the
      antibacterial effects of antibiotics or in the determinism of bacterial
      resistance to antibiotics is discussed.

PMID- 8264430
TI  - Formate dehydrogenase activity in methanol-utilizing yeasts.
AB  - The growth and activity of formate dehydrogenase (FDH) in five methanol-utilizing
      yeasts at various methanol concentrations were investigated. The parameters
      observed were inhibited at 4% methanol concentration in the medium. For Candida
      boidinii and Pichia trehalophila FDH activity was not found. The highest value
      was detected for Pichia lindneri (0.14 U/mg protein).

PMID- 8264431
TI  - Pheromone and insulin induced chemotaxis in Tetrahymena.
AB  - Cytodex spheres impregnated with insulin had a repellent effect at the first
      encounter and an attractive effect at the second encounter with Tetrahymena
      pyriformis. Tricosene, one of the two pheromones investigated had a positive
      chemotactic effect at the first encounter with the cells and this effect was
      increased following pretreatment (imprinting) with tricosene. Bornyl acetate
      expressed a negative effect on first use and was neutral on imprinted cells. The
      experiments demonstrate that not only hormones but also pheromones can serve as
      signal molecules for Tetrahymena. Moreover, the development of imprinting was
      observed. The effects and the imprintability were not a general characteristic of
      the pheromones which originate from the individual characters of the molecules.
      The development of imprinting can alter the direction of the effect of stimulus
      mediated by receptors.

PMID- 8264433
TI  - Comparison of fluorogenic and conventional membrane filter media for enumerating
      coliform bacteria.
AB  - 4-Methylumbelliferyl-beta-D-galactoside and 4-methylumbelliferyl-beta-D
      glucuronide were added to MacConkey broth and their diagnostic powers for total
      coliforms (TC) and Escherichia coli, respectively, were tested by membrane
      filtration at primary isolation. Examining water samples from different sources
      proved the usefulness of fluorogenic rather than reference media both as regards
      recovery efficiency and rapidity (possible within 12 h) of analyses. The
      recoveries obtained by fluorogenic and conventional tests for both TC and E. coli
      were correlated. Values were comparable in surface water samples, while a higher
      sensitivity of fluorogenic media was observed in samples of shallow contaminated
      ground water. Results seem to indicate that the use of fluorogenic membrane
      filtration analysis for colimetric indicators could be favourably considered
      especially for sanitary surveying of drinking water.

PMID- 8264432
TI  - Comparative effect of salinomycin and monensin on Streptococcus bovis strain ATCC
      9809.
AB  - The effect of salinomycin (2.5 mg/l) on the in vitro growth of Streptococcus
      bovis strain ATCC 9809, on its catabolism of glucose and on its anabolism of
      lactic acid was compared with that of monensin (5.0 mg/l). In control cultures
      containing no ionophore, glucose consumption and lactic acid production were
      completed concomitantly with maximal growth which was reached after 2 h of
      incubation at 37 degrees C. No further growth of S. bovis was observed within 2 h
      after the addition of one or the other ionophore to exponentially growing
      cultures. Glucose consumption and lactic acid production continued for 6 h after
      the addition of monensin and for 8 h after the addition of salinomycin. As
      observed in cultures without ionophore, glucose was totally consumed and lactic
      acid was stoichiometrically produced in cultures grown in the presence of one or
      the other ionophore. Thus, salinomycin and monensin inhibited bacterial growth
      but not fermentation of glucose by S. bovis.

PMID- 8264434
TI  - Contamination of bar soaps in a household setting.
AB  - The microbial content of fourteen bars of soap in a household setting was
      studied. The number of bacteria isolated from heavily used soaps which were wet,
      all placed in one bathroom, were higher than from infrequently used soaps that
      were dry and were placed in another bathroom. The major bacteria isolated were
      Staphylococcus sp. and Enterobacteriaceae.

PMID- 8264435
TI  - A simple and efficient continuous culture system for Helicobacter pylori.
AB  - Helicobacter pylori has been successfully maintained in a continuous culture
      system. The culture was grown in 0.6 litre of brain heart infusion broth with
      supplements in a 1 litre fermenter with a flow rate of 25 ml/h, an 80% dilution
      rate and a specific growth rate of 0.06/h. Unlike the typical growth curve which
      occurred in batch culture, the growth pattern in continuous culture showed a
      short lag phase following which growth was maintained in exponential phase with >
      or = 10-fold increase in viability and the pH was stabilised at 6.95 +/- 0.05.
      The urease activity remained constant in relation to viability while the urea was
      completely hydrolysed. The system provides cells with growth characteristics
      similar to the fresh isolate which are highly adaptable to the in vitro
      environment. This study shows that continuous culture is a simple and efficient
      growth system for the cultivation of a 'synchronous' spiral form of H. pylori.

PMID- 8264436
TI  - Phenotypic characterization of oral streptococci by classical methods.
AB  - The phenotypic characteristics of 215 strains of oral streptococci were compared
      on the basis of the results of sorbitol, raffinose and trehalose fermentation,
      ammonium from arginine production, aesculin hydrolysis, H2O2 production,
      susceptibility to 2 U bacitracin, and growth in 4% NaCl solution. Eleven
      different species were identified. Among the most noteworthy findings were the
      low number of H2O2-producing strains of Streptococcus sobrinus, the effective
      discrimination between Streptococcus sanguis and Streptococcus mitis on the basis
      of raffinose fermentation, and the phenotypic similarity between Streptococcus
      oralis and the former mutans group. To avoid the creation of new species, the
      term biotype is proposed to designate phenotypically distinct organisms which do
      not qualify as different species.

PMID- 8264437
TI  - Corporate practice of medicine.

PMID- 8264438
TI  - Burton Free Clinic. A point of light for Flint's indigent population.

PMID- 8264439
TI  - Health system reform--another false start?

PMID- 8264440
TI  - [Ultrastructure and properties of Actinobacillus actinomycetemcomitans].
AB  - In this study, plaque samples taken from periodontal pockets were cultured on
      Tryptic-soy-serum-bacitracin-vancomycin agar and identified according to colony
      morphology, Gram stain, catalase reaction and nitrate reduction tests after an
      incubation of 48 hours in candle jar. Cells identified as Actinobacillus
      actinomycetemcomitans were evaluated under the transmission electron microscope
      for fine structure. Outer membrane was observed as an irregular structure
      containing microcapsules. Unlike previous studies, periplasmic space was observed
      separately from other layers. Cytoplasmic membrane was observed surrounded by an
      electron-opaque cytoplasm. Besides, extracellular vesicles were seen extending to
      the outer environment around cytoplasmic membrane. Pathogenic properties of
      organelles were discussed. As a result, it was concluded that, in the future
      studies, products released and structural alterations occurring during growth of
      the organism, their pathologic effects and ways to suppress them need to be
      investigated microbiologically, ultrastructurally and biochemically.

PMID- 8264441
TI  - [Escherichia coli hemolysin: secretion kinetics and cytotoxic effect].
AB  - Escherichia coli hemolysin is one of the most important virulence determinants
      for uropathogenic strains. Hemolysin is cytotoxic to renal proximal tubular
      epithelial cells and leukocytes. It also causes the release of various mediators
      of inflammation and enzymes from leukocytes, thereby enhances the tissue damage
      to renal epithelium. The secretion kinetics of hemolysin was studied and found to
      be maximally secreted by an active process during logarithmic phase. The
      cytotoxic effect of the hemolysin was shown using Vero cells and by measuring
      Lactate Dehydrogenase activity in culture supernatants. The hemolytic strain
      showed significant cell lysis in comparison to non-hemolytic strain.

PMID- 8264442
TI  - [Evaluation of the ELISA method for the diagnosis of Helicobacter pylori].
AB  - Antibodies to H.pylori were investigated in the serum of 50 patients with
      dyspepsia and 25 healthy controls with ELISA method. The antibody positivity was
      found in all of the 40 cases (100%) for whom H.pylori was demonstrated in at
      least two tests of rapid urease, Gram stain, culture and silver staining and in
      eight of the ten cases (80%) whom H.pylori tests were all negative. Twenty-two of
      the 25 healthy controls (88%) had also antibodies to H.pylori. The sensitivity of
      the test was found high (100%), but the specificity was found too low (20%).

PMID- 8264443
TI  - [Detection of herpes simplex virus 1 and 2 (HSV-1 and HSV-2) IgG and IgM by ELISA
      in cord blood and sera of mothers with pregnancy complications].
AB  - In this study, HSV-1 IgG, IgM and HSV-2 IgG, IgM antibodies by ELISA in the sera
      of the mothers who had different kinds of obstetrical problems like abortus,
      stillbirth, prematurity, postmaturity, intrauterine development retardation and
      in the newborns' cord sera who had congenital anomalies like anencephaly,
      cataract and dolichocephaly were investigated. In these mothers HSV-1 IgG
      positivity ratio was 71/73 (97.3%). There was no significant difference in the
      age group distribution of HSV-1 IgG. The HSV-1 IgG positivity ratios in mother
      sera were the same as in cord sera. It was found that HSV-1 IgG antibodies passed
      transplacentally. It was established that one of the subjects had premature baby
      and the other had stillbirth inspite of HSV-1 IgG negativity but in the risk
      group subjects. HSV-1 IgM was found positive in 7 mothers (9.6%) of the study
      group. This data was the sign of active or reactive infection. There were 3
      abortus, 1 stillbirth and 3 anomalous baby in HSV-1 IgM seropositive mothers. In
      these mothers, 65/73 (89%) HSV-2 IgG and 6/73 (8%) HSV-2 IgM seropositivity were
      defined. In the cord sera these ratios were 65/73 (89%) and 2/73 (2.7%). IgM
      seropositivity of the material of the mothers who had abortus was explained by
      the effect of HSV-2 activity and the presence of HSV-2 IgM, 4 mothers were noted
      for the active or reactive infection sign. It was understood that HSV-2 IgG
      passed completely via placenta and there were no significant difference between
      the presence of the antibody and the age group.

PMID- 8264444
TI  - [Determination of hepatitis B markers in previously diagnosed hepatitis patients
      during a one-year period].
AB  - In this study, total 1699 sera collected from patients suspected viral hepatitis
      were investigated by means of Hepatitis B markers by ELISA method between June
      1991-June 1992 in Microbiology laboratory of Cumhuriyet University, Faculty of
      Medicine, Sivas. HBsAg, Anti-HBs and Anti-HBc IgM were screened as Hepatitis B
      markers. As a result, 16.9% of 1699 patients' sera were positive for HBsAg, 28.9%
      of 1318 sera were positive for Anti-HBs and 5% of 1056 sera were positive for
      Anti-HBc IgM. The results were discussed in terms of prevalence of Hepatitis B
      infection and carrier state.

PMID- 8264445
TI  - [Detection of Chlamydia trachomatis antigen in cases of cervicitis and patients
      with vaginal discharge].
AB  - This study was carried on 129 women of 16-62 age group, with complaints of
      vaginal discharge, genital itching and soreness, dysuria and pollakiuria.
      Endocervical specimens were investigated for Chlamydia trachomatis (C.
      trachomatis) antigen by ELISA. Risk factors for several gynecologic and obstetric
      pathologies and the role of C. trachomatis in mucopurulent cervicitis were
      emphasized. C. trachomatis antigen was found to be positive in 9 (7%) specimens.
      We concluded that, in cases of cervicitis, especially to prevent complications
      and social problems, the presence of C. trachomatis should also be investigated
      in addition to several viral, bacterial and fungal agents.

PMID- 8264446
TI  - [Detection of Chlamydia trachomatis in prostitutes working in a brothel in
      Izmir].
AB  - Endocervical specimens obtained from 251 registered prostitutes working in a
      brothel in Izmir, were screened for Chlamydia trachomatis by using a direct
      fluorescent antibody test. Twenty seven of these specimens were excluded because
      of inadequate sampling. Of the remaining 224 samples, 57 (25.4%) were found
      positive for C. trachomatis. It is concluded that, prostitutes play an important
      role in the transmission of chlamydial and other sexually transmitted diseases,
      and routine screening and appropriate treatment of chlamydial infections in
      prostitutes will help to control this disease in the general population.

PMID- 8264447
TI  - [Value of hypertonic media for the isolation of aberrant forms of Candida
      albicans from women with lower genital tract infections].
AB  - Women presenting symptoms and/or signs of lower genital tract infection were
      examined mycologically and to increase the sensitivity of the culture methods and
      to estimate the aberrant forms of fungi, hypertonic media was used. 47 yeast
      species were isolated from 86 patients. On the other hand 8 Candida albicans
      strains were isolated by using hypertonic culture media in which no growth was
      observed in any of the media used for routine culture. In relation with this
      study 8 cases were evaluated and the culture methods that have been used were
      discussed.

PMID- 8264448
TI  - [Detection of secretory acid proteinase enzyme from Candida strains on protein
      supplemented agar media].
AB  - In this study, we identified the species of 130 candida strains isolated from
      various clinical specimens, and we also investigated the secretory acid
      proteinase activity of these strains on hemoglobin, albumin and casein containing
      agar media. In 65 of 75 C. albicans, 8 of 15 C. tropicalis, 5 of 15 C.
      pseudotropicalis, in 3 C. stellatoidea and in 2 C. glabrata strains enzyme
      activity was shown. We couldn't detect proteinase activity in any of the 7 C.
      krusei, 7 C. parapsilosis and in 6 C. guilliermondii strains. Enzyme activity was
      shown to be inhibited when proteolytic strains were treated with specific
      inhibitor pepstatin-A.

PMID- 8264449
TI  - [Incidence of oral candidiasis in diabetic patients].
AB  - Yeast infections play an important role in diabetics. Therefore poorly controlled
      diabetics and diabetics who have high levels of serum glucose carry a high risk.
      In the present study, 52 diabetics aged between 17-75 years old have been
      investigated by means of the incidence of oral candida and have been compared
      with control group of 33 healthy individuals. In poorly controlled diabetics, the
      rate of candida growth found high. It is also observed that this ratio is higher
      in type I than type II, and candida growth rate increased as well as serum
      glucose level. All of these results are found to be statistically important.

PMID- 8264450
TI  - [Trichomonas vaginalis in women attending gynecology clinics].
AB  - In this study Trichomonas vaginalis was investigated in vaginal swab specimens
      from 234 women attending to the Gynecology Outpatient Clinics with various
      reasons. Trichomonas vaginalis was detected by wet mount in 8 women (3.4%) and,
      by culture using modified Diamond's medium in 9 women (3.8%). Of 9 cases only 2
      were suspected for trichomoniasis by gynecological examination.

PMID- 8264451
TI  - [The interrelationships of allergy, infection and the psyche].
AB  - In this review, we would attempt to discuss the interrelationships of allergy,
      infection, and the psyche. The interplay of these forces is expressed
      diagrammatically in Fig. 1.1, the interrelationship indicated there, suggests a
      dynamic interaction between three complex forces, each in itself capable of
      producing disease. In addition, since each affects the other, each may be able to
      initiate vicious cycles or chain-type reactions. On the other hand, we would
      attempt to discuss also, some specific and non-specific mechanisms involved in
      immunity as well as hypersensitivity reactions against to infectious agents. Fig.
      1.2, presents a simplification of the response of allergic patient to
      microorganisms. Immunity, hypersensitivity and unresponsiveness to different
      antigens of the same infectious agents can occur simultaneously.

PMID- 8264452
TI  - Tattoos and their removal.

PMID- 8264453
TI  - Do helmet wearing laws prevent bicycle injuries?

PMID- 8264454
TI  - The Diabetes Control and Complications Trial (DCCT). A milestone in diabetes
      management.

PMID- 8264455
TI  - Is HPV always sexually acquired?

PMID- 8264456
TI  - Acacias and aesculapius. Australian native wattles and the doctors they
      commemorate.
AB  - Acacias have had significant pharmacological, nutritive and toxicological
      associations with medicine since before recorded history, an interplay which
      continues to the present day. One of the most ubiquitous and loved symbols of
      Australia, and of Australian life and lore, indigenous wattles have also figured
      in the lives and memorials of medical practitioners. Some 20 indigenous Acacia
      species bear the names of medical explorers and clinical pioneers. This article
      documents some of the medical and related uses of Acacia by European and
      Aboriginal Australians and the evolution from this of a colonial herbal
      pharmacopoeia. It also gives brief precis and illustrations of the medical
      practitioners whose lives and works are immortalised in Australian native species
      of Acacia.

PMID- 8264457
TI  - Twenty Australian acacias and the doctors whose lives and works they commemorate.

PMID- 8264458
TI  - Operation Restore Hope. Military medical practice in Somalia.

PMID- 8264459
TI  - From psychosomatic medicine to consultation-liaison psychiatry.
AB  - OBJECTIVE: To trace the movement from psychosomatic medicine to consultation
      liaison psychiatry, the forces at work in shaping the change, and the extent to
      which the change is reflected in the latest revisions of the International
      classification of diseases (ICD-10) and the Diagnostic and statistical manual of
      mental disorders, third revision (DSM-III-R). DATA SOURCES AND SELECTION:
      Identification of important trends in the field was aided by discussions with
      fellow members of the panel of compilers of the consultation-liaison psychiatry
      literature review expert list published bi-annually in General Hospital
      Psychiatry. The expert list is based on appropriate literature searches. DATA
      SYNTHESIS: Psychosomatic medicine continues as a science, studying the
      relationships between biological, psychological and social phenomena in health
      and disease. The main advocates of the clinical application of the concepts and
      findings of psychosomatic medicine are now the general hospital consultation
      liaison psychiatrists and their allied health professional colleagues. The
      mainstreaming of psychiatry into medicine has accentuated the role of the
      consultation-liaison psychiatrist. In attempting to translate the advances in the
      field into a new taxonomy, both ICD-10 and DSM-III-R have created a new language
      that hinders understanding by a medical profession perhaps now less prone to
      resistance to holism. CONCLUSIONS: There is a need for a valid taxonomy that
      addresses the most common form of psychiatric presentation in the community, that
      of physical/psychiatric co-morbidity, and for outcome studies based on such a
      taxonomy. Consultation-liaison psychiatrists need to educate their colleagues
      about the changes in concepts and terminology.

PMID- 8264460
TI  - Drug smuggling by body packers. Detection and removal of internally concealed
      drugs.
AB  - International drug couriers frequently seek to evade detection by concealing
      drugs within the body. "Swallowers" swallow packages which they hope to retrieve
      after travelling; "stuffers" insert packages into the rectum or vagina. The
      danger of these practices is that packages can leak or burst, leading to a
      potentially fatal drug overdose. One drug courier arrested in South Australia had
      swallowed 143 separate parcels of heroin and morphine. Detection of concealed
      drugs is by abdominal, rectal or vaginal examination, aided by radiological
      investigation. Surgical removal may be required if swallowed packages burst or
      begin to leak. Doctors servicing prisons and airports need to be aware of how
      body packers can be detected and managed.

PMID- 8264461
TI  - A fatal case of cerebral artery gas embolism following fine needle biopsy of the
      lung.
AB  - OBJECTIVES: To report a case of cerebral artery gas embolism (CAGE), following
      fine needle biopsy of the lung, and to discuss the pathophysiology and treatment.
      CLINICAL FEATURES: A 65-year-old woman presented to an emergency department with
      the clinical features of a right thromboembolic stroke following a fine needle
      biopsy of the lung. INTERVENTIONS AND OUTCOME: Computed tomography (CT) was
      performed after an unexpected deterioration in the woman's condition. The CT
      demonstrated the presence of intracranial translucencies consistent with CAGE.
      Hyperbaric oxygen therapy was initiated but, despite two courses, the woman's
      condition continued to deteriorate and she died two days later. CONCLUSION: CAGE
      is a known but little appreciated complication of fine needle biopsy of the lung,
      and may be clinically indistinguishable from thromboembolic strokes. Successful
      treatment is dependent on early recognition and application of hyperbaric oxygen
      therapy, which appears to protect against injury and reverse many of the
      pathological changes associated with CAGE. The increasing popularity of fine
      needle biopsy of the lung as an outpatient procedure is likely to result in
      further presentations with CAGE to emergency departments.

PMID- 8264462
TI  - Emetine myopathy in a patient with an eating disorder.
AB  - OBJECTIVE: To alert physicians to the dangers of a readily available, non
      prescription drug by describing the clinical and pathological features of
      myopathy due to chronic poisoning with ipecac syrup in a patient with an eating
      disorder. CLINICAL FEATURES: A 27-year-old woman presented in 1991 with a right
      foot drop, followed a few months later by progressive severe neck and limb
      weakness associated with dysphagia, faecal incontinence and diffuse body ache. It
      emerged that she had been consuming increasing quantities of ipecac syrup (up to
      200 mL per week) for three months to induce vomiting and weight loss. The serum
      creatine kinase activity was slightly elevated and electromyographic examination
      results were in keeping with a necrotising proximal myopathic process. Muscle
      biopsy showed vacuolar degeneration with myofibrilolysis and fine cytoplasmic
      body formation, consistent with a diagnosis of emetine myopathy. INTERVENTION AND
      OUTCOME: The patient was advised to stop taking ipecac and observed for the next
      few months. The symptoms resolved gradually and strength returned to normal in
      four months. CONCLUSION: Chronic emetine toxicity, with its potentially
      catastrophic consequences, should be remembered in the evaluation of
      neuromuscular symptoms in young women, in whom eating disorders are common and
      often unrecognised.

PMID- 8264463
TI  - Acute aortic dissection in a patient with Marfan's syndrome complicated by
      gestational hypertension.
AB  - OBJECTIVE: To present a case of aortic dissection in a pregnant woman with
      Marfan's syndrome. CLINICAL FEATURES: A 34-year-old woman with Marfan's syndrome
      developed gestational hypertension and Type III aortic dissection during the
      third trimester. The diagnosis was confirmed by computed tomography and
      aortography. OUTCOME: Although the dissection progressed, the woman was treated
      successfully. Elective caesarean section was performed. At follow-up the
      dissection had healed. CONCLUSION: Marfan's syndrome introduces a high risk of
      aortic dissection during pregnancy and the treatment chosen is crucial. As
      dilatation of the aorta is progressive, patients with Marfan's syndrome should be
      followed up closely and offered prophylactic surgery if necessary.

PMID- 8264464
TI  - Perforated appendix in an inguinal hernial sac: Amyand's hernia.
AB  - A patient with a perforated appendix in a right inguinal hernial sac is reported.
      Some of the history of this condition is reviewed and a case is made that an
      appendix appearing in an inguinal hernial sac should carry the eponymous term
      "Amyand's hernia".

PMID- 8264466
TI  - Venomous bites and stings in the tropical world.
AB  - Snakes of the families Viperidae and Elapidae are responsible for the high
      incidence of morbidity and mortality after snake bites in countries of West
      Africa, the Indian subcontinent, South-East Asia, New Guinea and Latin America.
      Envenoming can cause local effects, notably tissue necrosis; and systemic
      effects, including paralysis, haemostatic disturbances, shock, increased
      capillary permeability, myocardial damage, rhabdomyolysis and acute renal
      failure. Specific hyperimmune serum (antivenom) is the mainstay of medical
      treatment for severe envenoming. Ancillary treatments such as assisted
      ventilation, repletion of circulating volume, renal dialysis and surgical
      debridement of necrotic tissues are needed in some cases. Scorpion stings are a
      common medical problem in middle and southern America, North Africa and the
      Middle East. Vasodilator drugs are important to counter the effects of massive
      catecholamine release. Bites by spiders and stings by hymenoptera and marine
      animals are responsible for deaths and morbidity in some tropical countries.

PMID- 8264465
TI  - The outcome of childhood Haemophilus influenzae meningitis. A population based
      study.
AB  - OBJECTIVE: To determine the morbidity and mortality from childhood Haemophilus
      influenzae type b (Hib) meningitis in a well defined population. DESIGN:
      Retrospective survey 1985-1987 and prospective surveillance of hospital
      laboratories 1989-1990. Information on outcome of meningitis was obtained from
      hospital records and attending physicians and, in 1989-1990, from a survey of the
      children's parents. SETTING: Sydney Statistical Division, which had a population
      of children aged 0-4 years of 229,165 in 1986 and 263,758 in 1990. PATIENTS:
      Eligible children were aged from one month to four years and had clinical and
      microbiological evidence of Hib meningitis on standard criteria. RESULTS: There
      were 229 eligible children. Twelve were excluded (seven died and five had pre
      existing neurological deficits). A neurological deficit was detected at the time
      of hospital discharge in 45 patients (21%) and persisted for 12 months or longer
      in 29 patients (13%). Follow-up information was available for 165 (96%) children
      who were normal at the time of hospital discharge and persistent deficits were
      recorded in 12 (7%) of these children. Forty-one children (19%) had readily
      recognisable neurological or hearing problems: nine (4%) had persistent severe
      neurological deficits and seven (3%) had severe hearing loss requiring hearing
      aids or a cochlear implant. Age had a significant influence on outcome. The
      youngest children were significantly more likely to be admitted to intensive
      care. Severe neurological deficits showed a significant negative trend with
      increasing age (P = 0.03). Severe unilateral or bilateral sensorineural loss
      (odds ratio [OR] 8.0, 95% confidence interval [CI] 1.5-81) and ataxia at
      discharge (OR 13.3, 95% CI 2.8-128) were noticeably more common in children over
      two years of age, with a significant positive trend (P < or = 0.001) with
      increasing age. Patients requiring intensive care were much more likely to have
      an adverse outcome, particularly if positive pressure ventilation was needed.
      CONCLUSIONS: These data provide population-based estimates of the minimum
      incidence of adverse outcomes from Hib meningitis in an urban community with good
      access to medical services. This is important in assessing the impact of Hib
      vaccination, as meningitis is responsible for most of the long-term morbidity
      from childhood invasive Hib disease. Determination of the relationship between
      morbidity and age is important for assessing alternative vaccine strategies.

PMID- 8264467
TI  - Psychiatry.

PMID- 8264468
TI  - Cycling fatalities in Western Australia.
AB  - OBJECTIVE: To present a review of the circumstances of 64 cycling fatalities in
      Western Australia (WA) during the nine-year period 1984-1992, and the major
      injuries sustained by the cyclists. DATA SOURCES: The number of deaths was
      ascertained from lists maintained by the WA Police Department, Forensic Pathology
      Division of the Health Department and the Coroner's office. Individual case files
      held by the Coroner's office and Forensic Pathology Division were then examined
      for details of the circumstances of each incident, epidemiological data, and
      medical and toxicological findings. DATA SYNTHESIS: Most of the 64 fatalities
      (59%) occurred in children or young adults less than 20 years of age. Most fatal
      injuries (54%) were to the head alone. Forty-seven of the deaths involved
      collision with a motor car. Alcohol was demonstrated in the blood of five of the
      30 cases in which analysis of blood alcohol level was performed. On average, 7.8
      cyclists died annually in WA before the introduction of legislation for the
      compulsory wearing of safety helmets while cycling. In the 12-month period
      following this legislation, there was only one cycling death. CONCLUSIONS: Most
      cycling deaths occur in children, primarily from head injury resulting from
      impact with a motor car. The enactment of legislation for the compulsory wearing
      of cycling helmets has been associated with a fall in cyclist fatalities.

PMID- 8264469
TI  - There are days ... and moons. Self-poisoning is not lunacy.
AB  - OBJECTIVE: To determine whether there are significant circadian, weekly or lunar
      variations in self-poisoning presentations and whether patients' names or dates
      of birth have an influence on the likelihood of self-poisoning by analysing
      biorhythms, numerology and star sign. SETTING: Hunter Valley, Australia.
      SUBJECTS: Consecutive adult patients admitted with self-poisoning between January
      1987 and June 1993. RESULTS: There were 2215 patients admitted. There was a
      marked circadian variation. Over 6% of all admissions occurred in each of the
      hours between 6 p.m. and 1 a.m. compared with less than 2% per hour between 5
      a.m. and 9 a.m. This pattern was not different for patients with a diagnosis of
      depression. Numerology, biorhythms and star signs had no significant correlations
      with self-poisoning, nor was there a significant weekly or yearly variation in
      presentations. There was a small but statistically significant sex difference in
      presentations analysed by lunar phases. At the new moon 60% of self-poisonings
      were in women, compared with 45% when the moon was full. The odds ratios (OR) for
      women to be admitted at full moon and at new moon were 1.27 (95% confidence
      interval [CI], 0.92-1.66; P value not significant) and 0.73 (95% CI, 0.57-0.92; P
      = 0.009) respectively. The mean illumination of the moon at the time of overdose
      was 50.63% +/- 0.91% for men, compared with 47.45% +/- 0.85% for women (P =
      0.014). CONCLUSION: The circadian cycle (but not weekly, yearly or mystical
      cycles) should be taken into account when determining staffing levels for poison
      information and casualty services. The full moon is protective for women.

PMID- 8264470
TI  - Doctors as healers.

PMID- 8264471
TI  - "O strong and long-liv'd death, how cam'st thou in?" Views of euthanasia from the
      17th century.

PMID- 8264472
TI  - Autonomy and paternalism in medicine.
AB  - The role of ethics in medical practice is now receiving close scrutiny, so it is
      timely that ethical concepts, such as autonomy and paternalism, be re-examined in
      their applied contexts. As neither autonomy nor paternalism has a current
      universally accepted meaning, their significance varies in both ethical and
      clinical discussion. Of the two, autonomy has moved further from its original
      moral context, to the extent that it often now signifies no more than a person's
      expressed intention. Paternalism, characterised as the antithesis of autonomy, is
      widely thought not to have any role in medicine. The transforming effects of
      illness, which may radically alter a person's decision making capacity, are
      commonly ignored.

PMID- 8264473
TI  - Diabetes Control and Complications Trial. Position statement of the Australian
      Diabetes Society.

PMID- 8264474
TI  - Under the overseas knife. The experiences of an Australian surgeon as a patient
      abroad.

PMID- 8264475
TI  - Family studies and the problems of inheritance.

PMID- 8264476
TI  - Pigmented lesions--a plan for management in general practice.
AB  - This article sets out a plan for examining and managing pigmented lesions in
      general practice based on risk categories, history and appearance at x10
      magnification. A family history of melanoma, sun exposure in the first 15 years
      of life, recent change and size above 7 mm should give concern. Benign lesions
      should not be removed from the "cape" area because of probable hypertrophic
      scarring.

PMID- 8264477
TI  - Fighting high cholesterol levels--lipid lowering drugs.

PMID- 8264478
TI  - Human insulin: lessons from the UK?

PMID- 8264480
TI  - Hib meningitis immediately after vaccination.

PMID- 8264479
TI  - When does Strongyloides autoinfection become hyperinfection?

PMID- 8264481
TI  - Rett's syndrome: opportunity for Australian study.

PMID- 8264482
TI  - Preventing acute gout when starting allopurinol therapy. Colchicine or NSAIDS?

PMID- 8264483
TI  - Effect of the novel 5-HT4 receptor agonist DAU 6236 in human colon.

PMID- 8264484
TI  - Resistance of Haemophilus influenzae type b to ampicillin mediated by ROB-1 beta
      lactamase.

PMID- 8264485
TI  - Fever associated with captopril.

PMID- 8264486
TI  - Hepatitis B transmission and skin infections.

PMID- 8264487
TI  - Animal experimentation and patients.

PMID- 8264488
TI  - Laparoscopic cholecystectomy.

PMID- 8264489
TI  - Nitrogen emphysema: a complication of cryotherapy.

PMID- 8264490
TI  - Prevention of HIV and HBV transmission in general practice.

PMID- 8264491
TI  - Spontaneous rupture of a malarial spleen.

PMID- 8264492
TI  - Depression in the elderly.

PMID- 8264493
TI  - Spironolactone induced agranulocytosis.

PMID- 8264494
TI  - Diabetes--national action plan.

PMID- 8264495
TI  - Meningoencephalitis in an adult with human herpesvirus-6 infection.

PMID- 8264496
TI  - Screening for neural tube defects.

PMID- 8264497
TI  - Digoxin-itraconazole interaction.

PMID- 8264498
TI  - The doctor as expert witness.

PMID- 8264499
TI  - The prevalence of tuberculosis infection in New South Wales police recruits, 1987
      1990.

PMID- 8264500
TI  - Serial murders are in the news again.

PMID- 8264501
TI  - The law and the media.

PMID- 8264502
TI  - Complaints and accountability--doctors and lawyers.

PMID- 8264503
TI  - Modes of admission of adult patients to mental hospitals since 1959: a comment.

PMID- 8264504
TI  - The female condom.

PMID- 8264505
TI  - Drugs for vomiting caused by cancer chemotherapy.

PMID- 8264506
TI  - Intestinal magnesium absorption.
AB  - Available data on the mechanism of Mg absorption is mainly descriptive in nature.
      There is data to support the existence of both gradient-driven and saturable Mg
      absorption. It is not clear, however, which process predominates under normal
      conditions. Evidence for a saturable process is based on a curvilinear
      relationship between dietary or luminal [Mg] and Mg uptake. Whether this is due
      to a carrier-mediated mechanism or due to alterations in absorption through the
      paracellular route remains to be determined. A careful review of the literature
      indicates that the predominate site of Mg absorption is the distal small
      intestine. Most of these studies, however, have been done in isolated segments
      which may not adequately reflect absorption in an undisturbed gastrointestinal
      tract. Future work will need to focus on identifying and characterizing Mg
      transport at the cellular and paracellular level as well as developing more
      sophisticated strategies for examining Mg absorption in the whole animal.

PMID- 8264507
TI  - Magnesium homeostasis and renal magnesium handling.
AB  - Magnesium is essentially an intracellular cation, which makes it difficult to
      evaluate magnesium status. About 1% of total body magnesium is present in serum
      and interstitial body fluid and only about 1% of the intracellular magnesium is
      in the free form, Mg2+. Recent studies show that this small fraction of free Mg2+
      rapidly changes with the extracellular magnesium. These free Mg2+ levels are
      carefully controlled within the cell and total cellular magnesium content are
      maintained at the expense of extracellular fluid and bone magnesium levels.
      Regulation of magnesium balance is met between intestinal absorption and renal
      excretion. The excretory side of magnesium balance involves appropriate changes
      in renal magnesium handling. Present evidence indicates that renal handling of
      magnesium normally is a filtration-reabsorption process; magnesium is filtered at
      the glomerulus and reabsorbed along the various segments making up the renal
      nephron. About 80% of total serum magnesium (0.7-1 mmol/l) is filtered at the
      glomerular membrane. Of the ultrafilterable magnesium (0.6-0.8 mmol/l) 20-25% is
      reabsorbed by the proximal tubule, including the convoluted and straight
      portions. Some 50-60% of the filtered magnesium is reabsorbed in the loop of
      Henle, specifically by thick ascending limb cells. The terminal nephron segments,
      including the distal convoluted tubule and collecting ducts, reabsorb only a
      small portion of the filtered magnesium (about 5-10%). The loop of Henle plays
      the major role in determining magnesium reabsorption and urinary magnesium
      excretion. The loop of Henle also is the segment in which the major regulatory
      factors act to maintain magnesium balance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264508
TI  - Hormonal control of renal magnesium handling.
AB  - In the kidney, the main site of magnesium transport is the thick ascending limb
      of Henle's loop which reabsorbs about 70% of filtered magnesium. In the mouse and
      rat, this reabsorption takes place essentially in the cortical portion of the
      thick ascending limb (cTAL). In the medullary portion (mTAL) the transport is not
      significantly different from zero, irrespective of the voltage, whereas in the
      cTAL, it is exclusively voltage-dependent. In the cTAL, up to six hormones
      (including PTH) or agonists can stimulate Mg transport. They are totally inactive
      in the mTAL. The data obtained in the mouse cTAL indicate that the hormone
      dependent increases in magnesium transport result from two synergistic effects:
      (1) a rise in the transepithelial voltage and (2) an increase in the permeability
      to magnesium of the paracellular shunt pathway.

PMID- 8264509
TI  - Abnormal renal magnesium handling.
AB  - The normal fractional urinary excretion of filtered magnesium is about 5%. In
      magnesium deficiency in man, the kidneys can normally reduce the 24-hour urinary
      magnesium excretion to less than 1 mmol (24 mg) via unknown mechanisms, and
      initially without a fall in plasma magnesium concentration. Renal magnesium
      wasting may be defined as a urinary excretion greater than 1 mmol/day in the
      presence of hypomagnesemia (plasma magnesium < 0.7 mmol/l). Congenital renal
      magnesium wasting occurs in several syndromes including Bartter's syndrome in
      which it is associated with hypercalciuria, and the defect may be in the thick
      ascending limb of Henle's loop, and Gitelman's syndrome in which there is
      hypocalciuria, and the defect may be in the distal convoluted tubule. Other
      causes of renal magnesium wasting include diabetes mellitus, hypercalcemia and
      diuretics. Magnesium wasting may also result from various toxicities including
      those of cis-platinum, in which the biochemical features resemble Gitelman's
      syndrome, and those of aminoglycosides, pentamidine and cyclosporin. Calcitriol
      deficiency may also contribute to renal magnesium wasting in some circumstances.
      Mild hypermagnesemia may occur in familial hypocalciuric hypercalcemia and may
      reflect abnormal sensitivity of the loop of Henle to calcium and magnesium ions.
      By contrast, the hypermagnesemia that occurs in chronic renal failure results
      from the reduced glomerular filtration of magnesium.

PMID- 8264510
TI  - Epithelial transport of magnesium in the kidney of fish.
AB  - That the kidneys of marine fish have powerful renal mechanisms for the excretion
      of magnesium (Mg) from the body has been known since the early 1930s, but it took
      another 40 years before the first renal Mg transport model was suggested by
      Natochin and Gusev. Since rates of net renal sodium (Na) reabsorption were
      closely correlated with rates of net renal Mg secretion in scorpion fish,
      Natochin and Gusev proposed tubular Na/Mg exchange transport. However,
      confirmation of Na/Mg exchange in other fish kidneys has been elusive. Detailed
      renal clearance studies in sea water rainbow trout have shown that bladder
      reabsorption of Na and water, the process which concentrates Mg in the bladder,
      accounts for much of Natochin's original observation. Nevertheless, studies of
      isolated perfused proximal tubules of the flounder and killifish do show inverse
      relationships between the concentrations of Na and Mg in the tubule lumen,
      consistent with Na/Mg exchange. Unfortunately, large paracellular Na
      permeabilities in renal proximal tubules do not clarify whether paracellular Na
      fluxes of Na/Mg exchange transport across the brush border membrane are
      responsible for generating inverse concentrations of Na and Mg in the tubule
      lumen. These uncertainties have led the authors to their present use of brush
      border membrane vesicles to look for evidence of Na/Mg exchange transport.

PMID- 8264511
TI  - Measurement of intracellular ionized magnesium.
AB  - Recent advances in methods for measuring Mgi have advanced our understanding of
      Mgi homeostasis. Several methods exist for measuring Mgi; all have strengths and
      weaknesses and one needs to match the experimental needs with the limitations of
      the method. For example, if one needs rapid (ms) time resolution, or only
      relative directional changes in a cell that is not easily impaled with an
      electrode, the fluorescent indicators may best suit ones needs. If on the other
      hand one wants to measure Mgi in a perfused organ, then the NMR methods may best
      address one's needs. If one needs to accurately know Mgi in a papillary muscle or
      some other tissue which is readily impaled then ion-selective microelectrodes may
      be the method of choice.

PMID- 8264512
TI  - Mechanisms and regulation of Mg2+ efflux and Mg2+ influx.
AB  - Net Mg2+ efflux occurred in human, chicken and rat erythrocytes, rat thymocytes
      and HL60 cells when the concentration of intracellular free Mg2+ ([Mg2+]i) was
      experimentally increased and proceeded until the original cellular Mg2+ content
      was reached, indicating induction and regulation of net Mg2+ efflux by increased
      [Mg2+]i. Net Mg2+ efflux was performed by electroneutral Na+/Mg2+ antiport,
      driven by the extra-/intracellular Na+ gradient. Na+/Mg2+ antiport was
      irreversible, performing only net Mg2+ efflux. Na+/Mg2+ antiport was inhibited by
      amiloride, quinidine and imipramine. Besides increased [Mg2+]i, Na+/Mg2+ antiport
      in thymocytes was regulated by cAMP which induced a maximal rate of Na+/Mg2+
      antiport. Net Mg2+ influx occurred when the cellular Mg2+ content was
      experimentally reduced and stopped when after reincubation in suitable media the
      original cellular Mg2+ content was reached, indicating regulation by [Mg2+]i via
      feedback inhibition. Net Mg2+ influx in isolated hepatocytes was dependent on
      extracellular Mg2+, Na+, Cl-, HCO3- and Pi. Net Mg2+ influx may operate via
      electroneutral Na+, Mg2+/anion cotransport, driven by the extra-/intracellular
      Na+ gradient. However, electrogenic Mg2+ influx gated by extracellular Na+ and
      anions cannot be excluded. Net Mg2+ influx was stimulated by cAMP and inhibited
      by amiloride and verapamil. Net Mg2+ efflux and net Mg2+ influx are separate and
      regulated pathways, establishing homeostasis of intracellular Mg2+.

PMID- 8264513
TI  - Molecular aspects of Mg2+ transport systems.
AB  - The gram-negative bacterium Salmonella typhimurium possesses three distinct Mg2+
      transport systems, encoded by the CorA, MgtA, and MgtB loci. The CorA transport
      system is the constitutive Mg2+ influx system but can also mediate efflux at high
      extracellular Mg2+ concentrations. The CorA protein lacks homology to any known
      protein, is an integral membrane protein containing 28% percent-charged amino
      acids, and has three carboxyl terminal membrane-spanning segments. Its properties
      indicate that it is a new class of membrane transport protein, likely found in
      all gram-negative bacteria and possibly other organisms. In contrast, the MgtA
      and MgtB Mg2+ transport systems are normally expressed only at low extracellular
      Mg2+ concentrations and can mediate only the influx of Mg2+. Both MgtA and MgtB
      system are P-type ATPases; they have relatively poor homology to other known
      prokaryotic P-type ATPases but are highly homologous to mammalian P-type ATPases,
      particularly reticular Ca(2+)-ATPases. Expression of both MgtA and MgtB is highly
      regulated by the concentration of extracellular Mg2+. Transcription of MgtB is
      increased about 1,000-fold by lowering Mg2+ from 1 mM to 1 microM, and, under
      growth conditions of limiting Mg2+, MgtB becomes the dominant Mg2+ influx system.
      However, it is unclear why the cells require the use of ATP to mediate the influx
      of Mg2+ down its electrochemical gradient. Study of these Mg2+ transport systems
      should lead to further understanding of cellular Mg2+ homeostasis and eventually
      to characterization of eukaryotic Mg2+ transport systems.

PMID- 8264514
TI  - Effects of intracellular magnesium on calcium, potassium and chloride channels.
AB  - Intracellular free magnesium activity approximates 0.6-0.8 mM. Variations in
      concentration around this physiologic range profoundly affect current flow
      through calcium, potassium and chloride channels. These effects are exerted on
      both inwardly and outwardly directed currents and appear to be independent of the
      state of phosphorylation of the channel. In the heart, these effects are
      manifested in changes in action potential duration, which may help to explain
      postulated links between hypomagnesemia and arrhythmias. In the kidney, effects
      of magnesium on ion channels may subserve a protective role and may explain how
      potassium balance is altered in magnesium depletion syndromes.

PMID- 8264515
TI  - Cell magnesium transport and homeostasis: role of intracellular compartments.
AB  - Magnesium transport across the plasma membrane of cardiac and liver cells appears
      to be under hormonal control. The increase in cytosolic cAMP, following the
      adrenergic stimulation of both cell types, results in a major Mg2+ efflux from
      perfused rat hearts or livers and from collagenase-dispersed ventricular myocytes
      or hepatocytes. By contrast, the activation of protein kinase C by carbachol,
      vasopressin, phorbol-myristate acetate or diacylglycerol analogs induces Mg2+
      accumulation in either of the experimental models. As for the role of
      intracellular compartments on Mg2+ homeostasis, the cAMP-mediated Mg2+ efflux
      largely depends on the mobilization of Mg2+ from mitochondria via the
      mitochondrial adenine nucleotide translocase. By contrast, Mg2+ influx appears to
      be related to the endo(sarco)plasmic reticulum and its dynamic handling of
      cytosolic Ca2+.

PMID- 8264516
TI  - Interrelationships of magnesium and potassium homeostasis.
AB  - The interrelationships of magnesium (Mg) and potassium (K) homeostasis are
      reviewed. Evidence from clinical and experimental studies including whole animal
      and cell culture experiments indicate that (1) homeostasis of Mg and K are
      closely related in the whole organism, (2) deficiencies of Mg and K frequently co
      exist with gastrointestinal and especially renal losses from diuretic and
      nephrotoxic drug treatment being mainly responsible, and (3) Mg is required for
      maintenance of normal cellular K. Evidence from many laboratories indicate that
      Mg has direct effects at a cellular level on K transport. These include effects
      on Na-K-ATPase, Na-K-Cl cotransport, K channels, charge screening and
      permeability effects on membranes. New data on positive correlations between Mg
      and K in cardiac tissue, skeletal muscle and lymphocytes from patients undergoing
      cardiopulmonary bypass are presented. Interrelationships in Mg and K in cardiac
      tissue have probably the greatest clinical significance in terms of arrhythmias,
      digoxin toxicity, and myocardial infarction. Future studies will be aimed at
      elucidating mechanisms of Mg-K interrelationships at a cellular level using new
      techniques with the ability to detect concentrations and modulations of free
      intracellular Mg.

PMID- 8264517
TI  - Magnesium and pregnancy.
AB  - Maternal and fetal magnesium homeostasis is reviewed. Current evidence suggests
      that pregnancy-associated growth is unlikely to cause maternal magnesium
      deficiency and that the case for magnesium supplementation during pregnancy is
      unproven. Similarly, data do not support the use of magnesium in prevention of
      preterm labor or its preferential use in tocolysis. Magnesium might have a role
      to play in the prevention/treatment of eclamptic seizures. Hypomagnesaemia occurs
      in poorly controlled diabetic pregnancy and may be part of the cause of the
      hypomagnesaemia in the infants of such mothers. Fetal magnesium homeostasis is
      poorly understood as is the mechanism of placental transfer. Data from the rat
      suggest that the bulk of maternofetal placental magnesium transfer occurs via a
      transcellular route utilising a Na+/Mg2+ exchanger and that maternofetal flux of
      magnesium is reduced in the presence of maternal diabetes mellitus. Further study
      of diabetic pregnancy will increase our understanding of magnesium homeostasis
      both in normal and abnormal pregnancy.

PMID- 8264518
TI  - Magnesium metabolism in childhood.
AB  - Hypomagnesemia in childhood is relatively frequently noted in the neonatal period
      due to maternal causes, such as decreased intake due to vomiting, overuse of
      laxatives, and neonatal causes such as intrauterine growth retardation, birth
      asphyxia and exchange transfusion. A very rare cause of neonatal magnesium
      deficiency is called primary hypomagnesemia caused by impaired intestinal
      absorption of magnesium. Reference values of serum magnesium in cord blood are
      slightly lowered. Erythrocyte magnesium content is also lowered in cord blood and
      during the first month after birth. Mononuclear magnesium content shows no
      differences with age. Renal magnesium loss is diagnosed by the presence of
      hypomagnesemia with an inappropriately high 24-hour urinary magnesium excretion.
      In isolated familial hypomagnesemia an autosomal dominant as well as an autosomal
      recessive mode of inheritance was found. The renal magnesium threshold is lowered
      in both forms but the tubular maximum is only lowered in the dominant form. In
      familial hypomagnesemia-hypokalemia (Gitelman syndrome) the renal magnesium
      threshold is lowered but the tubular maximum is in the normal range. In this
      syndrome, with probably an autosomal recessive mode of inheritance, the renal
      defect might be located in the distal nephron after the medullary part of the
      ascending limb of the loop of Henle. The magnesium content of mononuclear cells
      and erythrocytes is in the normal and lower normal range, respectively. In the
      familial hypomagnesemia-hypercalciuria syndrome, hypomagnesemia is always
      combined with hyperuricemia and nephrocalcinosis. Myopia and horizontal nystagmus
      are often present.

PMID- 8264519
TI  - Clinical manifestations of magnesium deficiency.
AB  - Magnesium (Mg) is critical for the function of numerous enzyme systems. Mg
      deficiency thereby may result in many and varied clinical manifestations. Mg
      deficiency is common as approximately 10% of patients admitted to city hospitals
      are hypomagnesemic. Mg deficiency is usually due to losses from the
      gastrointestinal tract or from the kidney. A serum Mg concentration of < 1.5
      mEq/l usually indicates Mg deficiency, however, intracellular Mg deletion may be
      present despite a normal serum Mg concentration. Acute clinical manifestations of
      Mg deficiency include neuromuscular hyperexcitability, cardiac arrhythmias, and
      biochemical abnormalities of hypokalemia and hypocalcemia. Chronic Mg depletion
      may contribute to hypertension, atherosclerotic vascular disease, altered glucose
      homeostasis, and metabolic bone disease. Therapy of the acute manifestations
      usually requires parenteral Mg administration of 24-48 mEq Mg/day for 3-5 days.
      Long-term Mg repletion may be accomplished by the administration of 300-600 mg of
      Mg orally/day.

PMID- 8264520
TI  - Magnesium, hypertensive vascular diseases, atherogenesis, subcellular
      compartmentation of Ca2+ and Mg2+ and vascular contractility.
AB  - Abnormal dietary deficiency in Mg as well as abnormalities in Mg metabolism
      appear to play important roles as risk factors for ischemic heart disease and
      acute myocardial infarction, namely in hypertensive vascular disease, diabetic
      vascular disease, insulin resistance, atherosclerosis and vasospasm.
      Experimental, epidemiological as well as clinical evidence that supports a role
      for Mg in these risk factors are reviewed. Extracellular Mg ions ([Mg2+]o) exert
      important actions upon divalent cation metabolism, transport and intracellular
      release of [Ca2+]i and intracellular free Mg ([Mg2+]i) in both vascular smooth
      muscle and endothelial cells. Digital imaging microscopy, using molecular
      fluorescent probes, clearly indicates that both intracellular free Ca2+ and
      intracellular free Mg2+ are compartmented in both vascular smooth muscle cells
      and endothelial cells. [Mg2+]o appears to exert important effects on the precise
      subcellular location and concentration of both [Ca2+]i and [Mg2+]i. Use of
      specific ion-selective electrodes for [Mg2+]o has revealed that [Mg2+]o can
      change more rapidly than heretofore believed in cardiovascular pathophysiologic
      states. The latter new findings therefore suggest that the ionized level of
      [Mg2+]o is an important determinant of vascular tone, contractility and
      reactivity.

PMID- 8264521
TI  - The ethics of pain management.

PMID- 8264522
TI  - Mississippi's granny midwives: pre and post Civil Wars.

PMID- 8264523
TI  - The expression and regulation of hsdK genes after conjugative transfer.
AB  - The type I restriction and modification genes of Escherichia coli can be
      transferred to other non-modified strains by conjugation without killing the
      recipient, implying that the restriction function must be regulated. In this
      study, two isogenic F' plasmids (r+K and r-K) served as donors in quantitative
      conjugation experiments with various restriction-deficient strains of E. coli and
      Salmonella typhimurium. Conjugation studies with hsd::lacZ operon fusions in F'
      plasmids indicate that both of the hsdK promoters, p(res) and pmod, express
      simultaneously following conjugative transfer. Thus these genes do not appear to
      be regulated at the transcriptional level. A spontaneous mutant of E. coli C was
      discovered that is presumably killed upon conjugative transfer of the hsdK genes
      (defined as a Crc- phenotype). The gene that is defective in the mutant was
      tentatively designated hsdC (control). Hfr gene replacement studies led to the
      localization of the putative hsdC gene between 6 and 16 min on the E. coli
      genetic map.

PMID- 8264524
TI  - Cloning, sequencing and enhanced expression of the Trichoderma reesei
      endoxylanase II (pI 9) gene xln2.
AB  - The Trichoderma reesei xln2 gene coding for the pI9.0 endoxylanase was isolated
      from the wild-type strain QM6a. The gene contains one intron of 108 nucleotides
      and codes for a protein of 223 amino acids in which two putative N-glycosylation
      target sites were found. Three different T. reesei strains were transformed by
      targeting a construct composed of the xln2 gene, including its promoter, to the
      endogenous cbh1 locus. Highest overall production levels of xylanase were
      obtained using T. reesei ALKO2721, a genetically engineered strain, as a host.
      Integration into the cbh1 locus was not required for enhanced expression under
      control of the xln2 promoter.

PMID- 8264525
TI  - Genetic and molecular characterization of embryonic mutants identified following
      seed transformation in Arabidopsis.
AB  - Over 5000 transgenic families of Arabidopsis thaliana produced following seed
      transformation with Agrobacterium tumefaciens were screened for embryonic
      lethals, defectives, and pattern mutants. One hundred and seventy-eight mutants
      with a wide range of developmental abnormalities were identified. Forty-one
      mutants appear from genetic studies to be tagged (36% of the 115 mutants examined
      in detail). Mapping with visible markers demonstrated that mutant genes were
      randomly distributed throughout the genome. Seven mutant families appeared to
      contain chromosomal translocations because the mutant genes exhibited linkage to
      visible markers on two different chromosomes. Chromosomal rearrangements may
      therefore be widespread following seed transformation. DNA gel blot
      hybridizations with 34 tagged mutants and three T-DNA probes revealed a wide
      range of insertion patterns. Models of T-DNA structure at each mutant locus were
      constructed to facilitate gene isolation. The value of such models was
      demonstrated by using plasmid rescue to clone flanking plant DNA from four tagged
      mutants. Further analysis of genes isolated from these insertional mutants should
      help to elucidate the relationship between gene function and plant embryogenesis.

PMID- 8264526
TI  - High frequency one-step gene replacement in Trichoderma reesei. I. Endoglucanase
      I overproduction.
AB  - The chromosomal cellobiohydrolase 1 locus (cbh1) of the biotechnologically
      important filamentous fungus Trichoderma reesei was replaced in a single-step
      procedure by an expression cassette containing an endoglucanase I cDNA (egl1)
      under control of the cbh1 promoter. CBHI protein was missing from 37-63% of the
      transformants, showing that targeting of the linear expression cassette to the
      cbh1 locus was efficient. Studies of expression of the intact cbh1-egl1 cassette
      at the cbh1 locus revealed that egl1 cDNA is expressed from the cbh1 promoter as
      efficiently as cbh1 itself. Furthermore, a strain carrying two copies of the cbh1
      egl1 expression cassette produced twice as much EG I as the amount of CBHI, the
      major cellulase protein, produced by the host strain. The level of egl1-specific
      mRNA in the single-copy transformant was about 10-fold higher than that found in
      the non transformed host strain, indicating that the cbh1 promoter is about 10
      times stronger than the egl1 promoter. The 10-fold increase in the secreted EG I
      protein, measured with an enzyme-linked immunosorbent assay (ELISA), correlated
      well with the increase in egl1-specific mRNA.

PMID- 8264527
TI  - High frequency one-step gene replacement in Trichoderma reesei. II. Effects of
      deletions of individual cellulase genes.
AB  - Four cellulase genes of Trichoderma reesei, cbh1, cbh2, egl1 and egl2, have been
      replaced by the amdS marker gene. When linear DNA fragments and flanking regions
      of the corresponding cellulase locus of more than 1 kb were used, the replacement
      frequencies were high, ranging from 32 to 52%. Deletion of the major
      cellobiohydrolase 1 gene led to a 2-fold increase in the production of
      cellobiohydrolase II; however, replacement of the cbh2 gene did not affect the
      final cellulase levels and deletion of egl1 or egl2 slightly increased production
      of both cellobiohydrolases. Based on our results, endoglucanase II accounts for
      most of the endoglucanase activity produced by the hypercellulolytic host strain.
      Furthermore, loss of the egl2 gene causes a significant drop in the filter paper
      hydrolysing activity, indicating that endoglucanase II has an important role in
      the total hydrolysis of cellulose.

PMID- 8264528
TI  - A novel response-regulator is able to suppress the nodulation defect of a
      Bradyrhizobium japonicum nodW mutant.
AB  - The two-component regulatory system Nod-VW of Bradyrhizobium japonicum is
      essential for the nodulation of the legume host plants Vigna radiata, V.
      unguiculata and Macroptilium atropurpureum. The NodV protein shares homology with
      the sensor-kinases, whereas the NodW protein is a member of the response
      regulator class. We report here the identification of a new B. japonicum DNA
      region that is able to suppress the phenotypic defect of a nodW mutant, provided
      that this region is expressed from a foreign promoter. The minimal complementing
      region, which itself is not essential for nodulation in a nodW+ background,
      consists of one gene designated nwsB (nodW-suppressor). The deduced amino acid
      sequence of the nwsB gene product shows a high degree of homology to NodW. The
      nws B gene is preceded by a long open reading frame, nwsA, whose putative product
      appears to be a sensor-kinase. Downstream of nwsB, an open reading frame encoding
      a second putative response-regulator was identified. Interspecies hybridization
      revealed the presence of nwsAB-like DNA also in other Bradyrhizobium strains.
      Using nwsB'-'lacZ fusions, the nwsB gene was found to be expressed rather weakly
      in B. japonicum. This low level of expression is obviously not sufficient to
      compensate for a nodW- defect, whereas strong overexpression of nwsB is a
      condition that leads to suppression of the nodW- mutation.

PMID- 8264529
TI  - Characterization of the terminal inverted repeats and their neighboring tandem
      repeats in the Chlorella CVK1 virus genome.
AB  - A unique group of large icosahedral viruses that infect a unicellular green alga
      (Chlorella sp. NC64A) were isolated from freshwater sources in Japan. These
      viruses contain a linear double-stranded DNA (dsDNA) genome with hairpin ends. A
      physical map was constructed for the genomic DNA of CVK1 (Chlorella virus
      isolated in Kyoto, no. 1) by pulsed-field gel electrophoresis of restriction
      fragments. The nucleotide sequences around both termini of the CVK1 DNA revealed
      the presence of inverted terminal repeats (ITR) of approximately 1.0 kb. Adjacent
      to the ITR, unique sequence elements of 10 to 20 bp were directly repeated 20 to
      30 times in tandem array. Several copies of these repeat elements were deleted in
      virus mutants that were occasionally generated from Chlorella cells that were in
      a putative CVK1 carrier state. These repeats might represent a hot spot of
      rearrangement in the CVK1 genome.

PMID- 8264530
TI  - A nuclear mutation conferring thiostrepton resistance in Chlamydomonas
      reinhardtii affects a chloroplast ribosomal protein related to Escherichia coli
      ribosomal protein L11.
AB  - We have isolated a nuclear mutant (tsp-1) of Chlamydomonas reinhardtii which is
      resistant to thiostrepton, an antibiotic that blocks bacterial protein synthesis.
      The tsp-1 mutant grows slowly in the presence or absence of thiostrepton, and its
      chloroplast ribosomes, although resistant to the drug, are less active than
      chloroplast ribosomes from the wild type. Chloroplast ribosomal protein L-23 was
      not detected on stained gels or immunoblots of total large subunit proteins from
      tsp-1 probed with antibody to the wild-type L-23 protein from C. reinhardtii.
      Immunoprecipitation of proteins from pulse-labeled cells showed that tsp-1
      synthesizes small amounts of L-23 and that the mutant protein is stable during a
      90 min chase. Therefore the tsp-1 phenotype is best explained by assuming that
      the mutant protein synthesized is unable to assemble into the large subunit of
      the chloroplast ribosome and hence is degraded over time. L-23 antibodies cross
      react with Escherichia coli r-protein L11, which is known to be a component of
      the GTPase center of the 50S ribosomal subunit. Thiostrepton-resistant mutants of
      Bacillus megaterium and B. subtilis lack L11, show reduced ribosome activity, and
      have slow growth rates. Similarities between the thiostrepton-resistant mutants
      of bacteria and C. reinhardtii and the immunological relatedness of Chlamydomonas
      L-23 to E. coli L11 suggest that L-23 is functionally homologous to the bacterial
      r-protein L11.

PMID- 8264531
TI  - Resolution of four large chromosomes in penicillin-producing filamentous fungi:
      the penicillin gene cluster is located on chromosome II (9.6 Mb) in Penicillium
      notatum and chromosome I (10.4 Mb) in Penicillium chrysogenum.
AB  - Four chromosomes were resolved by pulsed field gel electrophoresis in Penicillium
      notatum (10.8, 9.6, 6.3 and 5.4 Mb in size) and in five different strains of
      Penicillium chrysogenum (10.4, 9.6, 7.3 and 6.8 Mb in the wild type). Small
      differences in size were found between the four chromosomes of the five P.
      chrysogenum strains. The penicillin gene cluster was localized by hybridization
      with a pcbAB probe to chromosome II of P. notatum and to chromosome I of all P.
      chrysogenum strains except the deletion mutant P. chrysogenum npe10, which lacks
      this DNA region. The pyrG gene was localized to chromosome I in P. notatum and to
      chromosome II in all P. chrysogenum strains except in the mutant AS-P-78 where
      the probe hybridized to chromosome III. A major chromosomal rearrangement seems
      to have occurred in this high penicillin producing strain. A fast moving DNA band
      observed in all gels corresponds to mitochondrial DNA. The total genome size has
      been calculated as 32.1 Mb in P. notatum and 34.1 Mb for the P. chrysogenum
      strains.

PMID- 8264532
TI  - Characterization of the effectors required for stable inheritance of
      Streptococcus pyogenes pSM19035-derived plasmids in Bacillus subtilis.
AB  - The low-copy-number and broad-host-range pSM19035-derived plasmid pBT233 is
      stably inherited in Bacillus subtilis cells. Two distinct regions, segA and segB,
      enhance the segregational stability of the plasmid. Both regions function in a
      replicon-independent manner. The maximization of random plasmid segregation is
      accomplished by the recombination proficiency of the host or the presence of the
      pBT233 segA region. The segA region contains two open reading frames (orf) [alpha
      and beta]. Inactivation or deletion of orf beta results in SegA- plasmids. Better
      than random segregation requires an active segB region. The segB region contains
      two orfs (orf epsilon and orf zeta). Inactivation of either of the orfs does not
      lead to an increase in cell death, but orf zeta- plasmids are randomly
      segregated. These results suggest that pBT233 stabilization relies on a complex
      system involving resolution of plasmid oligomers (segA) and on the function(s)
      encoded by the segB region.

PMID- 8264533
TI  - An Arabidopsis gene homologous to mammalian and insect genes encoding the largest
      proteasome subunit.
AB  - A gene encoding a protein with extensive homology to the largest subunit of the
      multicatalytic proteinase complex (proteasome) has been identified in Arabidopsis
      thaliana. This gene, referred to as AtPSM30, is entirely encompassed within a
      previously characterized radiation-induced deletion, which may thus provide the
      first example of a proteasome null mutation in a higher eukaryote. However, the
      growth rate and fertility of Arabidopsis plants do not appear to be significantly
      affected by this mutation, even though disruption experiments in yeast have shown
      that most proteasome subunits are essential. Analysis of mRNA levels in
      developing seedlings and mature plants indicates that expression of AtPSM30 is
      differentially regulated during development and is slightly induced in response
      to stress, as has been observed for proteasome genes in yeast, Drosophila, and
      mammals. Southern blot analysis indicates that the Arabidopsis genome contains
      numerous sequences closely related to AtPSM30, consistent with recent reports of
      at least two other proteasome genes in Arabidopsis. A comparison of the deduced
      amino acid sequences for all proteasome genes reported to date suggests that
      multiple proteasome subunits evolved in eukaryotes prior to the divergence of
      plants and animals.

PMID- 8264534
TI  - Isolation of signaling mutants of tomato (Lycopersicon esculentum).
AB  - As a first step towards developing a genetic system for investigating signaling
      processes in plants, we have developed a screen for signaling mutants deficient
      in a wound response. We have isolated two mutants of tomato that lack detectable
      production of proteinase inhibitors induced systemically in leaves by wounding.
      The mutants are deficient in the induction of both proteinase Inhibitor I and
      proteinase Inhibitor II but can be induced to respond at near wild-type levels by
      methyl jasmonate, a known elicitor of inhibitor production in tomato. While
      completely deficient in systemic production of proteinase inhibitors, both
      mutants produce some proteinase inhibitor in wounded leaves. This evidence
      suggests the existence of two signaling pathways, one local and one systemic,
      that regulate the induction of proteinase inhibitor synthesis in response to
      wounding.

PMID- 8264536
TI  - Isolation and characterization of the SUD1 gene, which encodes a global repressor
      of core promoter activity in Saccharomyces cerevisiae.
AB  - The SUD1 gene was identified during a hunt for mutants that are able to express
      an sta1 gene (encoding an extracellular glucoamylase) lacking an upstream
      activation sequence (UAS) for transcription. A null allele of sud1 alleviated the
      transcriptional defect of the UAS-less sta1 and also suppressed mutations in
      trans-acting genes (GAM1/SNF2 and GAM3/ADR6) required for transcription of STA1.
      The mutation also increased expression from various core promoters (CYC1, CUP1,
      HIS3, PUT1, and PUT2), suggesting that the SUD1 protein is a global
      transcriptional regulator that plays a negative role at or near the TATA element.
      However, the SUD1 function was ineffective on promoters containing a UAS from
      either STA1 or GAL10 under derepressed conditions. The sud1 mutation suppressed
      the salt-sensitive cell growth phenotype caused by elevated levels of the TATA
      binding protein (SPT15), further suggesting a transcriptional role for SUD1. sud1
      cells showed additional pleiotropic phenotypes: temperature-sensitive (ts)
      growth, reduced efficiencies of sporulation, and sensitivity to heat shock and
      nitrogen starvation. The SUD1 gene is predicted to encode a 64 kDa, hydrophilic
      protein.

PMID- 8264535
TI  - Identification of a new class of nitrogen fixation genes in Rhodobacter
      capsulatus: a putative membrane complex involved in electron transport to
      nitrogenase.
AB  - DNA sequence analysis of a 12236 bp fragment, which is located upstream of nifE
      in Rhodobacter capsulatus nif region A, revealed the presence of ten open reading
      frames. With the exception of fdxC and fdxN, which encode a plant-type and a
      bacterial-type ferredoxin, the deduced products of these coding regions exhibited
      no significant homology to known proteins. Analysis of defined insertion and
      deletion mutants demonstrated that six of these genes were required for nitrogen
      fixation. Therefore, we propose to call these genes rnfA, rnfB, rnfC, rnfD, rnfE
      and rnfF (for Rhodobacter nitrogen fixation). Secondary structure predictions
      suggested that the rnf genes encode four potential membrane proteins and two
      putative iron-sulphur proteins, which contain cysteine motifs (C-X2-C-X2-C-X3-C
      P) typical for [4Fe--4S] proteins. Comparison of the in vivo and in vitro
      nitrogenase activities of fdxN and rnf mutants suggested that the products
      encoded by these genes are involved in electron transport to nitrogenase. In
      addition, these mutants were shown to contain significantly reduced amounts of
      nitrogenase. The hypothesis that this new class of nitrogen fixation genes
      encodes components of an electron transfer system to nitrogenase was corroborated
      by analysing the effect of metronidazole. Both the fdxN and rnf mutants had
      higher growth yields in the presence of metronidazole than the wild type,
      suggesting that these mutants contained lower amounts of reduced ferredoxins.

PMID- 8264537
TI  - Analysis of the frequency of inheritance of transposed Ds elements in Arabidopsis
      after activation by a CaMV 35S promoter fusion to the Ac transposase gene.
AB  - The Ac/Ds transposon system of maize shows low activity in Arabidopsis. However,
      fusion of the CaMV 35S promoter to the transposase gene (35S::TPase) increases
      the abundance of the single Ac mRNA encoded by Ac and increases the frequency of
      Ds excision. In the experiments reported here it is examined whether this high
      excision frequency is associated with efficient re-insertion of the transposon.
      This was measured by using a Ds that carried a hygromycin resistance gene (HPT)
      and was inserted within a streptomycin resistance gene (SPT). Excision of Ds
      therefore gives rise to streptomycin resistance, while hygromycin resistance is
      associated with the presence of a transposed Ds or with retention of the element
      at its original location. Self-fertilisation of most individuals heterozygous for
      Ds and 35S::TPase produced many streptomycin-resistant (strep(r)) progeny, but in
      many of these families a small proportion of strep(r) seedlings were also
      resistant to hygromycin (hyg(r)). Nevertheless, 70% of families tested did give
      rise to at least one strep(r), hyg(r) seedling, and over 90% of these individuals
      carried a transposed Ds. In contrast, the Ac promoter fusion to the transposase
      gene (Ac::TPase) produced fewer strep(r)hyg(r) progeny, and only 53% of these
      carried a transposed Ds. However, a higher proportion of the strep(r) seedlings
      were also hyg(r) than after activation by 35S::TPase. We also examined the
      genotype of strep(r), hyg(r) seedlings and demonstrated that after activation by
      35S::TPase many of these were homozygous for the transposed Ds, while this did
      not occur after activation by Ac::TPase. From these and other data we conclude
      that excisions driven by 35S::TPase usually occur prior to floral development,
      and that although a low proportion of strep(r) progeny plants inherit a
      transposed Ds, those that do can be efficiently selected with an antibiotic
      resistance gene contained within the element. Our data have important
      implications for transposon tagging strategies in transgenic plants and these are
      discussed.

PMID- 8264538
TI  - Transcriptional activation of the Drosophila melanogaster glucose-6-phosphate
      dehydrogenase gene by insertion of defective P elements.
AB  - Tandem insertions of defective P elements (1.15 kb KP and 0.6 kb core P)
      accelerate the transcription rate of the glucose-6-phosphate dehydrogenase (G6PD)
      gene in Drosophila melanogaster. In this report, we have analyzed the activation
      mechanism of the G6PD promoter by in vitro transcription and gel retardation
      assays. Results showed that one cis-acting region in the core P and two such
      regions in the KP are associated with activation of the G6PD promoter, and that
      putative transcriptional regulatory protein(s) which specifically bind to each of
      the cis-acting regions are present in nuclear extracts of Canton S embryos. On
      the other hand, the P elements do not activate the normal actin 5C promoter, but
      activate the promoter when the 20 bp sequence around the G6PD transcription start
      site is placed in front of the promoter. It appears that the GC-rich region in
      this 20 bp sequence is required for the activation.

PMID- 8264539
TI  - The Drosophila forked gene encodes two major RNAs, which, in gypsy or springer
      insertion mutants, are partially or completely truncated within the 5'-LTR of the
      inserted retrotransposon.
AB  - Mutations in the forked (f) gene of Drosophila cause deformation of bristles and
      hairs. Our molecular analysis showed the f gene to span more than 30 kb, and to
      encode two major RNAs, 6.0 and 2.5 kb long, both of which are prematurely
      terminated in gypsy and springer insertion mutants. These truncated RNAs were
      polyadenylated using putative polyadenylation signals within the 5'-LTR of the
      inserted retrotransposon. No evidence was found for effects of the
      retrotransposon insertions on the promoters for transcription of the 6.0 and 2.5
      kb RNAs. In f1 and fx, a single gypsy element was found to be inserted at
      identical sites in the second intron of region encoding the 2.5 kb f RNA and both
      truncated and wild-type sized RNAs were detected. Recessive mutations at
      suppressor of forked (su(f)) increased the fraction of wild-type sized RNAs
      considerably, suggesting that the wild-type su(f) product either stimulates
      premature termination at the gypsy LTR or inhibits normal splicing. In f36a, a
      springer element inserted in the third exon of the region encoding the 2.5 kb f
      RNA completely suppressed the formation of apparently wild-type transcripts.

PMID- 8264540
TI  - Characterisation of PDC2, a gene necessary for high level expression of pyruvate
      decarboxylase structural genes in Saccharomyces cerevisiae.
AB  - The regulatory gene PDC2 was identified in a screen for mutations affecting
      pyruvate decarboxylase activity in yeast. I have cloned and sequenced this gene.
      The predicted protein of 925 amino acids has no homology to any sequence in the
      databases. However, the protein sequence is rich in asparagine and serine
      residues, as is often found for transcriptional regulators. The PDC2 deletion
      mutant exhibits a phenotype very similar to, but more severe than that of the
      point mutant: a strongly reduced pyruvate decarboxylase specific activity, slow,
      respiration-dependent growth on glucose, and accumulation of pyruvate. The
      activity of other glycolytic enzymes seems to be unaffected by the pdc2 delta
      mutation. Synthesis of pyruvate decarboxylase is regulated by PDC2 at the
      transcriptional level. Expression of the major structural gene for pyruvate
      decarboxylase, PDC1, is strongly reduced in pdc2 delta mutants. Transcription of
      the generally more weakly expressed PDC5 gene appears to be entirely abolished.
      However, glucose induction of pyruvate decarboxylase synthesis is unaffected.
      Thus, PDC2 is either important for a high basal level of PDC gene expression or
      it plays a positive role in the autoregulation that controls expression of PDC1
      and PDC5.

PMID- 8264541
TI  - The mat- allele of Podospora anserina contains three regulatory genes required
      for the development of fertilized female organs.
AB  - In the filamentous fungus Podospora anserina, mating type is specified by a
      single locus with two alternate alleles, termed mat- and mat+. A previous study
      has shown that the mat+ sequence consists of 3.7 kb and contains a single gene
      relevant to the sexual cycle. This gene, called FPR1, encodes a protein with a
      HMG DNA-binding domain and is required for fertilization and for the development
      of the fertilized fruiting body. The mat- sequence, which is 4.7 kb in length,
      displays a more complex structure. We present here the characterization of two
      genes, called SMR1 and SMR2, which are present in the mat- allele along with the
      FMR1 gene. FMR1, whose role in the sexual cycle has been already partially
      described, encodes a protein with an alpha 1-domain and was shown to control
      fertilization. We demonstrate that these three genes are required for the
      developmental events that occur in the female organ after fertilization. The
      additional role of FMR1 requires a region of unknown function that is distinct
      from the alpha 1-domain. SMR1 encodes a protein with a putative
      acidic/hydrophobic alpha-helix, which has been proposed to be a feature common to
      transcriptional activators. The protein sequence deduced from SMR2 contains an
      HMG motif suggesting that it is a transcription factor.

PMID- 8264542
TI  - Co-regulation with genes of phospholipid biosynthesis of the CTR/HNM1-encoded
      choline/nitrogen mustard permease in Saccharomyces cerevisiae.
AB  - An 815 bp region of the promoter of the Saccharomyces cerevisiae gene CTR/HNM1,
      encoding choline permease was sequenced and its regulatory function analysed by
      deletion studies in an in-frame promoter-lacZ construct. In addition to the TATA
      box, a 10 bp motif (consensus 5'-CATGTGAAAT-3') was found to be mandatory for
      CTR/HNM1 expression. This 'decamer' motif is located between nucleotides -262 and
      -271 and is identical in 9 of 10 bp with the regulatory motif found in the S.
      cerevisiae INO1 and CHO1 genes. Constructs with the 10 bp sequence show high
      constitutive expression, while elimination or alterations at three nucleotide
      positions, of the decamer motif in the context of an otherwise unchaged promoter
      leads to total loss of beta-galactosidase production. Expression of the CTR/HNM1
      gene in wild-type cells is regulated by the phospholipid precursors inositol and
      choline; no such influence is seen in cells bearing mutations in the phospholipid
      regulatory genes INO2, INO4, and OPI1. There is no regulation by INO2 and OPI1 in
      the absence of the decamer motif. However constructs not containing this sequence
      (promoter intact to positions -213 or -152) are still controlled by INO4. Other
      substrates of the choline permease, i.e. ethanolamine, nitrogen mustard and
      nitrogen half mustard do not regulate expression of CTR/HNM1.

PMID- 8264543
TI  - Altered promoter binding of the TATA box-binding factor induced by the
      transcriptional activation domain of VP16 and suppressed by TFIIA.
AB  - The acidic transcriptional activation domain of the Herpes simplex virus protein
      VP16 has been shown to bind directly to both the TATA box-binding factor TBP and
      the general initiation factor TFIIB. Using DNase I footprinting assays, we have
      shown here that the VP16 activation domain qualitatively alters binding of
      Saccharomyces cerevisiae TBP to a TATA sequence in DNA. The effect of VP16 on
      promoter binding by TBP was reduced by mutations in VP16 known to reduce
      transactivation and could not be overcome by increasing the amount of TBP used in
      the footprinting assays. However, the association of yeast TFIIA with TBP on the
      promoter reversed the VP16-mediated effect and restored normal binding of TBP to
      the promoter. We suggest that VP16 induces a conformational change in TBP which
      alters its binding to promoter DNA, and that this effect of VP16 is suppressed by
      TFIIA.

PMID- 8264544
TI  - Cloning and mapping of the genetic determinants for microcin C51 production and
      immunity.
AB  - Microcin C51 is a small peptide antibiotic produced by Escherichia coli cells
      harbouring the 38 kb low copy number plasmid pC51, which codes for microcin
      production and immunity. The genetic determinants for microcin synthesis and
      immunity were cloned into the vectors pBR325, pUC19 and pACYC184. Physical and
      phenotypic analysis of deletion derivatives and mutant plasmids bearing
      insertions of transposon Tn5 showed that a DNA fragment of about 5 kb is required
      for microcin C51 synthesis and expression of complete immunity to microcin.
      Partial immunity can be provided by a 2 kb DNA fragment. Mutant plasmids were
      tested for their ability to complement Mic- mutations. Results of these
      experiments indicate that at least three plasmid genes are required for microcin
      production. The host OmpR function is also necessary for microcin C51 synthesis.

PMID- 8264545
TI  - Determination of the size of the Azotobacter vinelandii chromosome.
AB  - The chromosome of Azotobacter vinelandii UW was digested separately with the rape
      cutter restriction endonucleases SwaI (5'-ATTTAAAT), PmeI (5'GTTTAAAC) and PacI
      (5'-TTAATTAA) and the products were separated by pulsed-field gel
      electrophoresis. The size of the chromosome was determined to be approximately
      4.5 megabase pairs (Mb) based on the sum of the sizes of the restriction
      fragments. This is almost the same as the size of the chromosome of Escherichia
      coli. The inability of the undigested DNA to enter the gel has led us to infer
      that the chromosome is circular.

PMID- 8264546
TI  - Cycloheximide induces the alpha 1B adrenergic receptor gene by activation of
      transcription in DDT1 MF-2 smooth muscle cells.
AB  - alpha 1-Adrenergic receptors play important roles in mediating a wide range of
      important cellular responses; regulation of expression of these receptors may
      have pathophysiological significance in diseases such as hypertension. In order
      to pursue understanding of mechanisms involved in the regulation of expression of
      alpha 1 receptors, the effects of protein synthesis inhibitor cycloheximide on
      alpha 1B receptor gene expression were examined in DDT1 MF-2 smooth muscle cells.
      Cycloheximide markedly induced accumulation of the alpha 1B receptor mRNAs in a
      concentration- and time-dependent manner as detected by Northern blotting assays.
      The increased accumulation of alpha 1B receptor mRNA could be detected at 1 hr
      (1.7 +/- 0.2-fold) and the maximal accumulation occurred at 6 hr (5.4 +/- 0.3
      fold, p < 0.01). Nuclear runoff assays reveal that cycloheximide markedly
      increased the transcriptional rate of the alpha 1B receptor gene. The stability
      of alpha 1B receptor mRNAs measured by RNase protection assays was essentially
      unchanged by cycloheximide. Incubation of DDT1 MF-2 cells with two additional
      protein synthesis inhibitors, anisomycin and emetine, had similar effects to
      those of cycloheximide. However, a further inhibitor, puromycin, did not induce
      alpha 1B receptor mRNAs when protein synthesis was almost completely inhibited.
      Furthermore, puromycin did not inhibit the capacity of cycloheximide to induce
      transcription of the alpha 1B receptor gene. These observations suggest that
      cycloheximide induces alpha 1B receptor gene expression through direct activation
      of gene transcription rather than inhibition of protein synthesis.

PMID- 8264547
TI  - Cloning and characterization of a truncated dopamine D1 receptor from goldfish
      retina: stimulation of cyclic AMP production and calcium mobilization.
AB  - Receptors for dopamine are present on horizontal cells of fish retina that are
      linked to the activation of adenylate cyclase. In the present study, the goldfish
      (Carassius auratus) gene that encodes these receptors, referred to as gfD1, was
      isolated and analyzed. A single open reading frame within the gfD1 gene encodes a
      protein of 363 amino acids that is highly homologous with dopamine D1 receptors
      from rats and humans. Interestingly, the carboxyl terminus of gfD1 lacks 80 amino
      acids that are present in the mammalian receptor sequences. RNA analysis using
      the polymerase chain reaction demonstrated that the gene is expressed in the
      goldfish retina and is intronless within the coding region. The fact that gfD1
      encodes a dopamine D1 receptor was demonstrated through pharmacological analysis
      of transfected cells. Both the gfD1 receptor and the human D1 receptor expressed
      in mammalian cells had high affinity for SCH-23390 and other D1-specific ligands.
      In addition, the gfD1 receptor and the human D1 receptor were able to stimulate
      the accumulation of cAMP in response to SKF-38393 or dopamine. Interestingly,
      stimulation of both the gfD1 and human receptors with dopamine also resulted in
      an increase in intracellular Ca2+. Finally, long term pretreatment of transfected
      cells with dopamine resulted in the desensitization and down-regulation of both
      the goldfish and human receptors.

PMID- 8264548
TI  - Ethanol increases delta-opioid receptor gene expression in neuronal cell lines.
AB  - Long-term treatment with ethanol increases delta-opioid receptor (DOR) expression
      in the NG108-15 neuroblastoma x glioma hybrid cell line. To determine the
      underlying mechanism, we studied the effects of ethanol on [3H]diprenorphine
      binding to intact cells and DOR gene expression in four related clonal neural
      cell lines. Incubation with 200 mM ethanol for 48 hr increased [3H]diprenorphine
      binding by 1.4- (N18TG2), 1.8- (NG108-15), 1.9- (N4TG1), and 3.0-fold (N1E-115).
      Treatment with 25, 50, or 100 mM ethanol for 1 week caused a dose-dependent
      increase in receptor expression. Receptor up-regulation was associated with an
      increase in the potency of etorphine for inhibiting prostaglandin E1-stimulated
      cAMP accumulation. Constitutive DOR expression differed more than 3-fold among
      the different cell lines and correlated positively with basal cAMP levels. Long
      term ethanol treatment increased basal cAMP levels in three of the four cell
      lines, but did not induce cellular differentiation. Northern blot analysis
      demonstrated an identical pattern of multiple transcripts in the four cell lines.
      Ethanol increased the abundance of DOR mRNA by approximately 3-fold in N18TG2
      cells and by approximately 5-fold in the remaining cell lines. These findings
      indicate that clinically relevant concentrations of ethanol regulate DOR
      expression by increasing the abundance of DOR mRNA. The disparity between the
      increase in gene expression and ligand binding suggests that ethanol may also
      modify mRNA translation or receptor processing.

PMID- 8264549
TI  - pH-dependent inactivation of DT-diaphorase by mitomycin C and porfiromycin.
AB  - Mitomycin C and porfiromycin were found to inactivate rat hepatic DT-diaphorase.
      Inactivation was pH dependent; little inactivation was detected at pH 5.8, but
      inactivation increased as the pH was raised to 7.8. Inactivation was
      concentration and time dependent and displayed pseudo-first-order kinetics.
      Inactivation was NADH dependent, indicating that reductive metabolism was
      necessary for inhibition. [3H]Mitomycin C was covalently bound to DT-diaphorase
      during inhibition, and the stoichiometry for inactivation of DT-diaphorase by
      mitomycin C was approximately 0.8 nmol of mitomycin C bound/nmol of enzyme. A
      higher molecular mass product (60 kDa) was detected by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and Western blot analysis of DT-diaphorase
      preincubated with NADH and mitomycin C at pH 7.8, suggesting that mitomycin C is
      capable of cross-linking DT-diaphorase. The kinetics of inhibition, requirement
      for NADH for inhibition, covalent binding of [3H] mitomycin C to DT-diaphorase,
      and approximate 1:1 stoichiometry suggest that this inactivation process may be
      mechanism based. Inhibition of DT-diaphorase by mitomycin C and porfiromycin is
      not limited to a cell-free system and could also be observed in HT-29 cells in
      culture at pH 7.2. Bioactivation of mitomycin C or porfiromycin by DT-diaphorase
      is favored at lower pH, whereas at higher pH values enzyme alkylation and
      inactivation of DT-diaphorase occur. These data suggest that the success of
      attempts to exploit the elevated DT-diaphorase content of certain human tumors
      for improved chemotherapeutic response using mitomycin C or porfiromycin will
      depend on intracellular pH.

PMID- 8264550
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin increases cardiac myocyte intracellular
      calcium and progressively impairs ventricular contractile responses to
      isoproterenol and to calcium in chick embryo hearts.
AB  - Binding by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the Ah receptor leads to
      transcriptional activation of several genes and a toxicity syndrome that includes
      tumor promotion, wasting, hormonal and immune system dysfunction, and death.
      Recent findings indicate that TCDD may also affect cardiac function. Here, we
      used the chick embryo, a TCDD-sensitive species, to further characterize the
      effects of TCDD on ventricular muscle contraction and on cardiac myocyte [Ca2+]i
      assessed with fura 2. The results show that TCDD causes an evolving sequence of
      contractile defects, independent of changes in diet, first impairing cAMP
      modulated contraction (after 48 hr) and later (by seven days) decreasing
      responses to [Ca2+]o. Phenobarbital, even at high doses, failed to affect the
      inotropic response to isoproterenol, supporting the specificity of the
      ventricular contractile effects of TCDD. TCDD treatment also depressed inotropic
      responses to theophylline and forskolin, indicating that it has a post-beta
      adrenergic receptor effect on cAMP action. In contrast to its depression of
      responses to beta-adrenergic stimuli and to [Ca2+]o, TCDD did not affect initial
      tensions of ventricular muscle stimulated at 1 Hz or the force-frequency response
      up to 1 Hz, indicating that TCDD-treated ventricles can respond normally at slow
      rates of stimulation. TCDD treatment depressed lusitropic (relaxation) responses
      to isoproterenol and to increasing [Ca2+]o indicating that it impairs the ability
      of the sarcoplasmic reticulum to sequester Ca2+. Fura 2-based measurements showed
      that [Ca2+]i was nearly doubled after TCDD treatment. The increase in [Ca2+]i is
      consistent with the decrease in the contractile response to [Ca2+]o, amelioration
      of the response to isoproterenol by subphysiologic concentrations of [Ca2+]o, and
      intermittent lack of response to electrical stimulation in high K+ observed in
      ventricles from TCDD-treated embryos. TCDD treatment also depressed the initial
      increase in [Ca2+]i by isoproterenol, consistent with the decreased contractile
      response to isoproterenol. The findings show that TCDD causes well defined,
      progressive impairment of avian ventricular responses to inotropic stimuli,
      providing new evidence that the heart is a target of TCDD action and that TCDD
      disturbs intracellular calcium processing.

PMID- 8264551
TI  - Monoclonal antibody AE-2 modulates carbamate and organophosphate inhibition of
      fetal bovine serum acetylcholinesterase.
AB  - The monoclonal antibody AE-2, raised against the human erythrocyte
      acetylcholinesterase (AChE) dimer (acetylcholine acetylhydrolase, EC 3.1.1.7),
      binds to other mammalian AChEs, including the tetramer that occurs in fetal
      bovine serum (FBS). AE-2 partially inhibited the rate of hydrolysis of the
      charged substrate acetylthiocholine by FBS AChE, whereas it increased the rate of
      hydrolysis of the neutral substrate indophenyl acetate. Present results show that
      AE-2 decreases the rate of inhibition of FBS AChE by the positively charged
      organophosphate amiton-p-toluene sulfonate and the positively charged carbamates
      pyridostigmine and neostigmine but accelerates inhibition of FBS AChE by the
      neutral organophosphates paraoxon and diisopropylfluorophosphate. Results suggest
      that AE-2 may allosterically modulate an anionic site in the catalytic center of
      FBS AChE.

PMID- 8264552
TI  - Human m3 muscarinic acetylcholine receptor carboxyl-terminal threonine resides
      are required for agonist-induced receptor down-regulation.
AB  - The mechanisms involved in agonist-induced down-regulation of the human m3
      muscarinic acetylcholine receptor were investigated by site-directed mutagenesis
      of the receptor cytoplasmic carboxyl terminus. Threonine residues
      (Thr550,553,554) were converted into alanines collectively and individually. The
      mutated and wild-type receptor cDNAs stably expressed in Chinese hamster ovary
      cells displayed similar antagonist- and agonist-binding properties. Furthermore,
      mutant receptors showed the same efficacy and potency for carbachol-induced
      activation of phosphoinositide hydrolysis as did the wild-type clone. In all
      cases the maximal increase in phosphoinositide hydrolysis was 8-9-fold. In
      contrast to normal intracellular signaling, however, the mutant receptor with all
      three threonines changed to alanines (Ala550,553,554) failed to undergo normal
      down-regulation in response to carbachol. After a 24-hr incubation in the
      presence of 1 mM carbachol, subsequent N-[3H]methylscopolamine binding was
      reduced by 66% for the wild-type clone but by only 12% for the mutant receptor.
      The Ala553,554 mutant also showed a profound reduction in receptor down
      regulation. Subsequent studies showed that a small but significant blockage of
      receptor down-regulation also could be produced by converting a single threonine
      residue (Thr553) to alanine. The fact that these effects were not due to
      nonspecific conformational changes was suggested by the lack of effects on
      binding, signal transduction, and down-regulation of converting Thr550 to alanine
      or converting two cysteine residues (Cys561,563) to glycines in an adjacent
      region. A similar reduction in receptor number also was observed in binding
      studies using the membrane-permeant ligand [3H]scopolamine. These results show
      that threonine residues in the carboxyl-terminal domain of the human m3
      muscarinic acetylcholine receptor are important in agonist-induced receptor down
      regulation.

PMID- 8264553
TI  - Selective irreversible binding of chloroethylclonidine at alpha 1- and alpha 2
      adrenoceptor subtypes.
AB  - We have determined the alkylating effects and affinity of chloroethylclonidine at
      alpha 1- and alpha 2-adrenoceptor subtypes in saturation and competition
      radioligand binding studies. Treatment with chloroethylclonidine (10 microM, for
      30 min at 37 degrees, with subsequent washout) abolished [3H]prazosin binding to
      alpha 1B-adrenoceptors in rat spleen almost completely and reduced specific
      binding in rat kidney and cerebral cortex by a percentage comparable to the known
      alpha 1B-adrenoceptor content of these tissues. Chloroethylclonidine treatment
      also markedly reduced [3H]rauwolscine binding to human platelet and kidney
      membranes but did not affect [3H]rauwolscine binding to rat kidney. Similar
      chloroethylclonidine treatment (10 microM, 20 min at 37 degrees) reduced the
      number of detectable alpha 2-adrenoceptors in cell lines transfected with the
      alpha 2-C10 or alpha 2-C4 gene but not in those transfected with alpha 2-C2
      adrenoceptors. In concentration-response experiments, higher chloroethylclonidine
      concentrations were required for inactivation of human platelet alpha 2A
      adrenoceptors, compared with rat spleen alpha 1B-adrenoceptors, and a smaller
      maximal inactivation was achieved. The lack of inactivation of rat alpha 1A- and
      alpha 2B- and human alpha 2-C2-adrenoceptors was not due to a lack of
      chloroethylclonidine binding, because the affinity of chloroethylclonidine at
      these subtypes, as determined in competition binding experiments, was at least as
      high as the apparent affinity at the alkylated subtypes. alpha 2A-Adrenoceptor
      alkylation by chloroethylclonidine treatment was functionally relevant, because
      it significantly reduced alpha 2A-adrenoceptor-mediated Ca2+ elevations in HEL
      cells. We conclude that chloroethylclonidine binds to all major alpha
      adrenoceptor subtypes and irreversibly inactivates not only alpha 1B
      adrenoceptors but also alpha 2A- and alpha 2C-adrenoceptors, whereas alpha 1A-
      and alpha 2B-adrenoceptors are relatively resistant to its alkylating action,
      although they can bind chloroethylclonidine.

PMID- 8264554
TI  - Stable allosteric binding of m1-toxin to m1 muscarinic receptors.
AB  - m1-Toxin was found to slow the dissociation of [3H]N-methyl-scopolamine (NMS) and
      [3H]pirenzepine from m1 muscarinic receptors expressed in the membranes of
      Chinese hamster ovary cells. When toxin-NMS-receptor complexes were formed in
      membranes and then dissolved in digitonin, or when these complexes were formed in
      solution, the toxin completely stopped the dissociation of [3H]NMS for 6 hr at 25
      degrees C. Toxin-receptor complexes formed in membranes or in solution were also
      highly stable in solution at 25 degrees, as shown by the ability of the toxin to
      prevent the binding of [3H]quinuclidinyl benzilate (QNB). [3H] QNB-receptor
      complexes were equally stable, whereas unliganded soluble receptors lost most of
      their ability to bind QNB within an hour. Toxin-receptor complexes could be
      partially dissociated by incubation at 37 degrees in the presence of digitonin
      and [3H]QNB, and the freed receptors were then labeled. These results demonstrate
      that m1-toxin binds allosterically and pseudoirreversibly to m1 receptors, and
      that the toxin can stabilize the outward-facing pocket of m1 receptors which
      contains and binds competitive antagonists. The allosteric nature of the binding
      of m1-toxin should prove to be useful for such unusual purposes as stabilizing
      the binding of readily reversible and/or nonselective ligands specifically to m1
      receptors, for purifying labeled or unlabeled receptors by affinity techniques
      which recognize the toxin, for recognizing receptors with genetically or
      biochemically altered primary binding sites, and for stabilization of the native
      conformation of m1 receptors for structural studies.

PMID- 8264555
TI  - P2U-purinergic receptors on C6-2B rat glioma cells: modulation of cytosolic Ca2+
      and cAMP levels by protein kinase C.
AB  - The activation of P2-purinergic receptors on C6-2B rat glioma cells caused a
      transient increase in cytosolic-free Ca2+ concentration ([Ca2+]i) as detected by
      Fura 2 fluorescence ratio imaging of single cells. These purinergic receptors are
      of the P2U subtype because UTP and ATP were equipotent and substantially more
      potent than the P2X- and P2Y-selective agonists alpha,beta-methylene ATP and 2
      methylthio ATP, respectively. There was homologous desensitization of the Ca2+
      responses between UTP and ATP but no heterologous desensitization between these
      nucleotides and another Ca(2+)-mobilizing receptor agonist, alpha-thrombin. The
      UTP-induced peak [Ca2+]i rise was insensitive to chelation of extracellular Ca2+
      with EGTA. However, the response was abolished after either depletion of
      intracellular Ca2+ stores with the microsomal Ca(2+)-ATPase inhibitor
      thapsigargin or blockade of Ca2+ release from intracellular stores with the
      muscle relaxant dantrolene. The activation of P2U-purinergic receptors and
      thrombin receptors increased the formation of total inositol phosphates (IPs) and
      inhibited cAMP accumulation elicited with either the beta-adrenergic receptor
      agonist (-)-isoproterenol, or forskolin, a direct activator of adenylyl cyclase.
      UTP- and alpha-thrombin-induced changes in the levels of IPs, cytosolic Ca2+, and
      agonist-elicited cAMP accumulation were dramatically inhibited (> 80%) by acute
      treatment of the cells with the protein kinase C activator 4 beta-phorbol 12
      myristate 13-acetate but not with the inactive ester 4 alpha-phorbol 12,13
      didecanoate. We conclude that in C6-2B cells, the increase in [Ca2+]i after
      activation of P2U-purinergic receptors is primarily a result of IPs-mediated
      release of Ca2+ from intracellular stores with secondary influx of Ca2+ by
      capacitative mechanisms. Also, the inhibition by UTP and alpha-thrombin of
      agonist-elicited cAMP accumulation is mediated through an increase in [Ca2+]i.

PMID- 8264556
TI  - Chlorocresol: an activator of ryanodine receptor-mediated Ca2+ release.
AB  - In the present study we investigated the effect of the compound chlorocresol on
      intracellular Ca2+ homeostasis. Three different systems that have been shown to
      express the ryanodine receptor Ca2+ channel were chosen, i.e., skeletal muscle
      sarcoplasmic reticulum, cerebellar microsomes, and PC12 cells. In skeletal muscle
      sarcoplasmic reticulum, 4-chloro-m-cresol was found to be a potent activator of
      Ca2+ release mediated by a ruthenium red/caffeine-sensitive Ca2+ release channel.
      In cerebellar microsomes, this compound released Ca2+ from an inositol-1,4,5
      trisphosphate-insensitive store, suggesting that there too it was acting at the
      ryanodine receptor level. When tested on PC12 cells, chlorocresol released Ca2+
      from a caffeine- and thapsigargin-sensitive intracellular store. In addition, the
      compound was capable of releasing Ca2+ after pretreatment of PC12 cells with
      bradykinin, suggesting that it acts on a channel contained within an
      intracellular Ca2+ store that is distinct from that sensitive to inositol-1,4,5
      trisphosphate. Structure-activity relationship analyses suggest that the chloro
      and methyl groups in chlorocresols are important for the activation of the
      ryanodine receptor Ca2+ release channel.

PMID- 8264557
TI  - Enhancement of recombinant gamma-aminobutyric acid type A receptor currents by
      chronic activation of cAMP-dependent protein kinase.
AB  - alpha 1, beta 1, and gamma 2S gamma-aminobutyric acid (GABA) type A receptor
      (GABAR) subunit cDNAs were transiently expressed in derivative cell lines of
      mouse L929 fibroblasts, which possessed different levels of the catalytic subunit
      of cAMP-dependent protein kinase (PKA). These cell lines included L929
      (intermediate levels of kinase), C alpha 12 (elevated levels of kinase), and
      RAB10 (low levels of kinase) cells. Pharmacological analysis of GABA-evoked whole
      cell currents revealed that, compared with expression in L929 and RAB10 cells,
      expression of alpha 1 beta 1 gamma 2S GABARs in C alpha 12 cells produced a
      selective enhancement of single whole-cell current amplitudes. No other
      pharmacological properties (Hill slope, EC50, or diazepam sensitivity) of the
      expressed alpha 1 beta 1 gamma 2S GABARs were modified. The GABAR current
      enhancement in C alpha 12 cells was blocked by substitution of a beta 1 subunit
      mutated at the PKA consensus phosphorylation site, Ser409 [beta 1(S409A)], for
      the wild-type beta subunit. Interestingly, enhancement was specific for GABARs
      containing all three subunits, because it was not seen after expression of alpha
      1 beta 1 or alpha 1 beta 1 (S409A) GABAR subunit combinations. Single-channel
      conductance and gating properties were not different for alpha 1 beta 1 gamma 2S
      or alpha 1 beta 1 (S409A) gamma 2S GABARs expressed in each cell line, suggesting
      that PKA did not enhance whole-cell currents by altering these properties of
      GABARs. These results suggested that unlike acute application of PKA, which has
      been shown to produce a decrease in GABAR current, chronic elevation of PKA
      activity can result in enhancement of GABAR currents. More importantly, this
      effect occurred only with GABARs composed of alpha 1 beta 1 gamma 2S subunits and
      not alpha 1 beta 1 subunits and was mediated by a single amino acid residue
      (Ser409) of the beta 1 subunit.

PMID- 8264558
TI  - Role of the beta subunit in determining the pharmacology of human gamma
      aminobutyric acid type A receptors.
AB  - A cDNA encoding the human gamma-aminobutyric acid (GABA)A receptor beta 2 subunit
      has been cloned and sequenced. The deduced amino acid sequence of this cDNA shows
      only a single amino acid change from the rat sequence (Asn-347 in rat, serine in
      human). Using polymerase chain reaction amplification of human-specific products
      from human x rodent somatic cell hybrid DNAs, the gene has been assigned to human
      chromosome 6. By expressing recombinant human GABAA receptors containing
      different beta subunits (beta 1, beta 2 or beta 3) in both transfected cells and
      Xenopus oocytes, we have been able to determine the influence of the beta subunit
      on the pharmacology of the receptor. For a number of benzodiazepine binding site
      compounds, a barbiturate, and several neurosteroids, neither the affinity nor the
      efficacy of the compounds is influenced by the type of beta subunit present in
      the receptor molecule. These data suggest that the beta subunit does not
      significantly influence the benzodiazepine, barbiturate, or steriod site
      pharmacologies of human GABAA receptor subtypes.

PMID- 8264559
TI  - Cycloalkanemethanols discriminate between volume- and length-dependent loss of
      activity of alkanols at the Torpedo nicotinic acetylcholine receptor.
AB  - Primary normal alcohols (1-n-alkanols) exert two effects on the nicotinic
      acetylcholine receptor when added simultaneously with agonist. First, propanol
      through decanol inhibit the open channel. Second, methanol through butanol, but
      not higher homologs, increase the apparent affinity of the agonist for inducing
      cation flux. To test the hypothesis that the length or volume of the alcohols
      might account for the fact that some members of the 1-n-alkanol homologous series
      lack activity, we have studied in parallel 11 members of another homologous
      series, i.e., the cycloalkanemethanols, c(CnH(2n-1)CH2OH. With steadily
      increasing potency, agents from cyclopropanemethanol to cyclodecanemethanol
      completely inhibited carbachol-stimulated 86Rb+ efflux from nicotinic
      acetylcholine receptor-rich postsynaptic vesicles from the electroplaques of
      Torpedo nobiliana, but even 90% saturated solutions of cycloundecanemethanol
      inhibited only part of the flux and neither cyclododecanemethanol nor
      cyclotetradecanemethanol caused any inhibition. Comparison of these results with
      those previously obtained for 1-n-alkanols indicates that as both series are
      ascended the cut-off in the inhibitory action on the channel occurs when the
      volume of the compounds exceeds approximately 340 A3. The apparent affinity for
      carbachol-induced flux was enhanced only by cyclopropanemethanol through
      cyclooctanemethanol, consistent with the hypothesis that a critical length of
      approximately 6.3 A cannot be exceeded. Thus, the sites mediating the two effects
      have different steric requirements and may be physically distinct.

PMID- 8264560
TI  - New sigma-like receptor recognized by novel phenylaminotetralins: ligand binding
      and functional studies.
AB  - Several novel phenylaminotetralins (PATs) cause functional changes in brain that
      are associated with binding to saturable, high affinity sites that are not
      identical to any known central nervous system receptor. These PATs were tested
      for their ability to cause receptor-mediated functional effects on tyrosine
      hydroxylase activity in corpus striatum from rat and guinea pig brain. (+/-)
      (trans)-1-Phenyl-3-dimethylamino-6-chloro-7-hydroxy-1,2,3,4-
      tetrahydronaphthalene (CI, OH-PAT) increased tyrosine hydroxylase activity (by
      approximately 30-40%) at 0.1 microM. Higher concentrations inhibited enzyme
      activity by indirect mechanisms that may include displacement of intraneuronal
      dopamine. The 6,7-unsubstituted congener (+/-)-(trans)-1-phenyl-3-dimethylamino
      1,2,3,4- tetrahydronaphthalene stimulated tyrosine hydroxylase by as much as 50
      60% over basal activity, without displacement of dopamine. Similarly to certain
      (+)-benzomorphan sigma receptor ligands, the effects of both PATs to activate
      tyrosine hydroxylase were blocked competitively by the putative sigma antagonist
      BMY-14802. Radiolabeled [3H]CI,OH-PAT bound saturably and with high affinity to
      guinea pig brain membranes (Kd = 31 pm, Bmax = 6.5 fmol/mg of protein). The
      pharmacological profile of these binding sites was inconsistent with those of
      known sigma 1, sigma 2, dopaminergic, serotonergic, adrenergic, opioid, N-methyl
      D-aspartate, or several other characterized central nervous system recognition
      sites. Together, these data suggest that these PATs may be agonists at a novel
      sigma-like site that has neuromodulatory activity that results in increases of
      brain catecholamine synthesis via activation of tyrosine hydroxylase.

PMID- 8264561
TI  - Effects of terfenadine and its metabolites on a delayed rectifier K+ channel
      cloned from human heart.
AB  - Use of the nonsedating antihistamine terfenadine has been associated with altered
      cardiac repolarization in certain clinical settings. For this reason we examined
      the effects of terfenadine, and its metabolites, on a rapidly activating delayed
      rectifier K+ channel (fHK) cloned from human heart. fHK was stably expressed in
      human embryonic kidney cells, and both whole-cell currents and currents from
      excised inside-out patches were recorded. Terfenadine (3 microM) blocked whole
      cell fHK current by 72 +/- 6%. In inside-out patches, terfenadine applied to the
      cytoplasmic surface blocked fHK with an IC50 value of 367 nM. The main effect of
      terfenadine was to enhance the rate of inactivation of fHK current and thereby
      reduce the current at the end of a prolonged voltage-clamp pulse. The blockade
      displayed a weak voltage dependence, increasing at more positive potentials. The
      mechanism of action of terfenadine is therefore consistent with blockade of open
      channels. In contrast, the metabolites of terfenadine were weakly active on fHK.
      IC50 values for all of the metabolites tested ranged from 27-fold to 583-fold
      higher than that obtained for terfenadine. It is concluded that terfenadine, but
      not its metabolites, blocks at least one type of human cardiac K+ channel at
      clinically relevant concentrations and that this activity may underlie the
      cardiac arrhythmias that have been associated with the use of this drug.

PMID- 8264562
TI  - Molecular mechanism of delta-selectivity of indole analogs of nonpeptide opioids.
AB  - A combined experimental and computational approach was used to understand the
      mechanism of delta-receptor selectivity of a series of nonpeptide opioids. Six
      pairs of fused ring opioids/indole derivatives were studied. Receptor-binding
      assays using [3H][D-Ala2-MePhe4-Gly-ol]-enkephalin (mu), [3H][D-Pen2-D-Pen5]
      enkephalin (delta), and [3H]U-69593 (kappa) were performed in guinea pig whole
      brain membranes. Agonist activity was determined in norbinaltorphimine- or beta
      funaltrexamine-treated guinea pig ileum (mu and kappa) and beta-funaltrexamine
      treated mouse vas deferens (delta). Steric and electronic properties were
      calculated for each compound. Although the parent compounds were selective for
      the mu-receptor, the indole analogs displayed selectivity for the delta-site
      because of a decrease in mu-affinity accompanied by an increase in delta
      affinity. The indole analogs displayed little or no activity at the delta
      receptor. The role of the indole in enhanced delta-recognition is likely
      interaction with a lipophilic site in the receptor. The diminished mu-affinity of
      the indole analogs is a result of the loss of the carbonyl oxygen as the proton
      accepting center, which we have previously determined to be important for
      recognition of the mu-receptor.

PMID- 8264563
TI  - Phosphorylation of the enantiomers of the carbocyclic analog of 2'-deoxyguanosine
      in cells infected with herpes simplex virus type 1 and in uninfected cells. Lack
      of enantiomeric selectivity with the viral thymidine kinase.
AB  - CdG, the carbocyclic analog of 2'-deoxyguanosine, is active against herpes,
      hepatitis B, and human cytomegaloviruses. We have studied the interaction of the
      tritiated enantiomers of CdG with the herpes simplex virus type 1-specific
      thymidine kinase (HSV-1 TK) and have examined their metabolism in uninfected and
      HSV-1-infected cells. D- and L-CdG were equally effective competitive inhibitors
      of the phosphorylation of thymidine (dThd) by the partially purified HSV-1 TK (Ki
      values were 2.1 and 3.4 microM, respectively) and were also equal as substrates
      (Km values were 17 and 26 microM, respectively, and Vmax values of the
      enantiomers were equal and about 50% greater than the Vmax for dThd). The
      partially purified enzyme preparation, which contained cellular nucleotide kinase
      activities (pyruvate kinase also was present in the assay medium), converted D
      CdG almost exclusively to the triphosphate and L-CdG almost exclusively to the
      monophosphate. Similarly, in virus-infected cells the D-enantiomer was converted
      predominantly to the triphosphate and the L-enantiomer predominantly to the
      monophosphate. In uninfected cells the results were qualitatively similar. In CEM
      cells deoxycytidine (dCyd) kinase (EC 2.7.1.74) seemed to be the enzyme
      principally responsible for the phosphorylation of both enantiomers, as shown by
      competition studies. Thus, both the HSV-1 TK and cellular dCyd kinase (of CEM
      cells) showed no selectivity for the enantiomers of CdG. This lack of
      enantiomeric specificity has obvious implications for the design of inhibitors of
      both viral proliferation and cellular metabolism.

PMID- 8264564
TI  - Cytochrome P450 2B1-mediated one-electron reduction of adriamycin: a study with
      rat liver microsomes and purified enzymes.
AB  - The role of cytochrome P450 (CYP) in the one-electron reductive bioactivation of
      Adriamycin (ADR) (doxorubicin) was investigated in subcellular fractions of the
      rat liver. The rate of one-electron reduction of ADR to its semiquinone free
      radical (ADRSQ), measured by ESR, was 5-fold greater with phenobarbital (PB)
      induced (PB microsomes) than with beta-naphthoflavone (beta NF)-induced (beta NF
      microsomes) rat liver microsomes under anaerobic conditions. ADRSQ formation was
      inhibited by SK&F 525-A and metyrapone (MP) in PB microsomes but was not
      significantly inhibited in beta NF microsomes. Under aerobic conditions, the
      formation of ADRSQ from ADR was diminished in microsomal incubations and
      concomitant reduction of molecular oxygen occurred instead. Whereas ADR-induced
      H2O2 formation in PB microsomes was strongly inhibited by SK&F 525-A and MP, only
      a slight inhibition was observed with 2-ethylnylnaphthalene and 1-ethynylpyrene
      in beta NF microsomes. In addition, MP produced strong inhibition of ADR
      stimulated lipid peroxidation in PB microsomes, compared with beta NF microsomes.
      The idea that CYP2B1 was involved in the one-electron reduction of ADR in PB
      microsomes and in reconstituted systems of purified CYP2B1 and purified NADPH-CYP
      reductase (RED) under anaerobic conditions could be concluded from inhibition
      studies using SK&F 525-A and antibodies (KO1) against CYP2B enzymes. Moreover, it
      was calculated from reconstitution experiments using varying amounts of purified
      CYP2B1 and purified RED that the contribution of CYP2B1 to the one-electron
      reduction of ADR was similar to that of RED alone.

PMID- 8264565
TI  - Molecular cloning and expression of a pituitary somatostatin receptor with
      preferential affinity for somatostatin: 28.

PMID- 8264566
TI  - Determination of phosphotyrosine phosphatase (PTPase) activity in normal and
      transformed cells.
AB  - Through the development of a new colorimetric and non-radioactive method it is
      possible to measure PTPase activity in cell extracts. Applying this method we
      were able to demonstrate that intracellular PTPase activity in chicken embryo
      fibroblasts increases significantly after RSV induced transformation of these
      cells. PTPase activity in normal and transformed cells is inhibited by microM
      concentrations of vanadate, molybdate and zinc ion, but is not affected by mM
      concentrations of calcium, magnesium and sodium fluoride. The transformation
      specific activation of the PTPase seems to represent an early parameter during
      the events of cellular transformation.

PMID- 8264567
TI  - Acute treatment with tumour necrosis factor-alpha induces changes in protein
      metabolism in rat skeletal muscle.
AB  - Acute treatment of rats with recombinant tumour necrosis factor (TNF-alpha)
      caused an enhanced proteolytic rate--measured as tyrosine released in the
      presence of cycloheximide-in soleus muscle (34%). The cytokine treatment also
      decreased the rate of protein synthesis in this muscle (22%) while it had no
      effect upon the same parameter in extensor digitorum longus (EDL) (26%) muscle.
      In addition, treatment of rats with TNF-alpha increased amino acid uptake by
      transport system A in the incubated muscles both in soleus (45%) and EDL (99%) in
      the presence of insulin in the incubating medium. This effect was not associated
      with a direct action of TNF on muscle since the addition of different
      concentrations of the cytokine to the preparations did not alter the uptake of
      alpha(methyl)-aminoisobutyric acid by the incubated muscles. It can be concluded
      that acute TNF-alpha treatment causes changes in protein metabolism in red-type
      muscles-such soleus-while little effects are seen in white-type muscles-such as
      EDL. The results presented may, to some extent, be related to the cachectic
      response associated with cancer and inflammation.

PMID- 8264568
TI  - Effects of glycated albumin on mesangial cells: evidence for a role in diabetic
      nephropathy.
AB  - Nonenzymatically glycated proteins are preferentially transported across the
      glomerular filtration barrier, and the glomerular mesangium in diabetes is bathed
      with serum containing increased concentrations of glycated albumin. We
      investigated effects of glycated albumin on mesangial cells, which are involved
      in diabetic nephropathy. [3H]-thymidine incorporation was significantly inhibited
      when murine mesangial cells were grown in culture media containing human serum
      that had been nonenzymatically glycated by incubation for 4 days with 28 mM
      glucose. This inhibition was reversed when monoclonal antibodies that selectively
      react with Amadori products of glycated albumin were added to the culture media.
      Purified glycated albumin containing Amadori adducts of the glycation reaction
      induced significant inhibition of thymidine incorporation and stimulation of Type
      IV collagen secretion compared with cells cultured in the presence of purified
      nonglycated albumin. These changes were prevented when monoclonal antibodies
      specifically reactive with fructosyl-lysine epitopes in glycated albumin were
      added to the cultures. The antibodies had no effect on growth or collagen
      production in the presence of nonglycated albumin. The results provide the first
      evidence directly implicating Amadori adducts in glycated albumin in the
      pathogenesis of diabetic nephropathy, which is characterized by decreased
      cellularity in association with expansion of the mesangial matrix.

PMID- 8264569
TI  - Effect of statil on kidney structure, function and polyol accumulation in
      diabetes mellitus.
AB  - We examined the effects of an aldose-reductase inhibitor, statil, which blocks
      the conversion of glucose to sorbitol, in rats rendered diabetic with
      streptozotocin in order to determine whether the anticipated changes in sorbitol
      content was associated with beneficial lack of changes in renal morphology and
      function. Groups of diabetic, insulin-treated and untreated rats were fed statil
      daily for a period of five months; each group was paired with a non-drug
      treatment control group. At the conclusion of the study period, statil was not
      found to affect renal sorbitol concentrations nor did it effect functional or
      structural changes seen in the kidney. We conclude that further study, using
      other doses of statil and longer duration over which data is collected, must be
      undertaken in order to implicate the polyol pathway in the renal complications of
      diabetes mellitus.

PMID- 8264570
TI  - Metabolic studies on rabbit bladder smooth muscle and mucosa.
AB  - Recent studies indicate that the mucosa of the urinary bladder may play a major
      role in the maintenance of normal bladder function. The mucosal surface of the
      urinary bladder serves as a protective layer against the irritative solutes found
      in the urine. The integrity of this barrier can be broken by overdistension,
      anoxia, detergents, alcohols, bacterial infection and by contact with agents to
      which the mucosa has been sensitized. In view that both anoxia and ischemia can
      mediate a breakdown in the role of the mucosal layer as a permeability barrier,
      it is reasonable to assume that this function is dependent on cellular
      metabolism. As an initial investigation we have compared a variety of biochemical
      and metabolic parameters between the mucosal layer (consisting of the lamina
      propria, urothelium, and any connective tissue and vascular tissue within this
      layer); and the muscularis layer. The results of these studies demonstrated that
      the rate of glucose metabolism to lactic acid (LA) of the mucosa was more than
      three-fold greater than that of the smooth muscle. The rate of CO2 production of
      the mucosa was 60% greater than that of the unstimulated smooth muscle. The
      maximal activity of the mitochondrial enzyme citrate synthase was significantly
      greater in the mucosa than in the smooth muscle, however, the activity of malate
      dehydrogenase was similar for both tissues. The maximal activity of the cytosolic
      enzyme creatine kinase was more than two-fold greater in the bladder smooth
      muscle than in the mucosa; although the affinities of the creatine kinase
      isoforms of the mucosa were significantly greater than those of the
      muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264571
TI  - Characterization of Ca(2+)-stimulated adenosine 5'-triphosphatase and Ca2+
      sequestering in rat liver nuclei.
AB  - The role of Ca(2+)-stimulated adenosine 5'-triphosphatase (Ca(2+)-ATPase) in Ca2+
      sequestering of rat liver nuclei was investigated. Ca(2+)-ATPase activity was
      calculated by subtracting Mg(2+)-ATPase activity from (Ca(2+)-Mg2+)-ATPase
      activity. Ca2+ uptake and release were determined with a Ca2+ electrode. Nuclear
      Ca(2+)-ATPase activity increased linearly in the range of 10-40 microM Ca2+
      addition. With those concentrations, Ca2+ was completely taken up by the nuclei
      dependently on ATP (2 mM). Nuclear Ca(2+)-ATPase activity was decreased
      significantly by the presence of arachidonic acid (25 and 50 microM),
      nicotinamide-adenine dinucleotide (NAD+; 2 mM) and zinc sulfate (2.5 and 5.0
      microM). These reagents caused a significant decrease in the nuclear Ca2+ uptake
      and a corresponding elevation in Ca2+ release from the nuclei. Moreover,
      calmodulin (10 micrograms/ml) increased significantly nuclear Ca(2+)-ATPase
      activity, and this increase was not seen in the presence of trifluoperazine (10
      microM), an antagonist of calmodulin. The present findings suggest that Ca(2+)
      ATPase plays a role in Ca2+ sequestering by rat liver nuclei, and that calmodulin
      is an activator. Moreover, the inhibition of Ca(2+)-ATPase may evoke Ca2+ release
      from the Ca(2+)-loaded nuclei.

PMID- 8264572
TI  - Is brain a gluconeogenic organ?
AB  - Glucagon increased the activities of alanine amino transferase (AAT), fructose
      1:6-bisphosphatase (fru-P2ase) and glucose-6-phosphatase (G-6-Pase) in goat brain
      tissue by about 100%, 150% and 50% respectively. These increase in activities
      were reversed by beta-antagonists propranolol. Well known alpha-agonist and
      antagonist like phenylephrine and phenoxybenzamine also increased AAT and G-6
      Pase activities and these increased activities were reversed by propranolol.
      Phenylephrine and phenoxybenzamine however did not increase brain Fru-P2ase
      activity. However the most interesting finding is that cerebral cortical slices
      could produce glucose from alanine and this glucose production was enhanced by
      glucagon, phenylephrine and phenoxybenzamine. Propranolol reversed the effects of
      these agonists and antagonist to a great extent. From all these experiments we
      suggest brain to be a gluconeogenic organ although much less efficient than
      liver.

PMID- 8264573
TI  - Effect of Plumbagin on some glucose metabolising enzymes studied in rats in
      experimental hepatoma.
AB  - Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) isolated from Plumbago
      zeylanica Linn, when administered orally, at a dosage of 4 mg/kg body weight
      induces tumour regression in 3-methyl-4-dimethyl aminoazobenzene (3MeDAB) induced
      hepatoma in Wistar male rats. The purpose of this investigation was to identify
      the changes in the rate of glycolysis and gluconeogenesis in tumour-bearing rats
      and the effects of treatment with Plumbagin. The levels of certain glycolytic
      enzymes, namely, hexokinase; phosphoglucoisomerase; and aldolase levels increased
      (p < 0.001) in hepatoma bearing rats, whereas they decreased in Plumbagin
      administered rats to near normal levels. Certain gluconeogenic enzymes, namely,
      glucose-6-phosphatase and fructose-1,6-diphosphatase decreased (p < 0.001) in
      tumour hosts, whereas Plumbagin administration increased the gluconeogenic enzyme
      levels in the treated animals. These investigations indicate the molecular basis
      of the different biological behaviour of 3MeDAB induced hepatoma and the
      anticarcinogenic property of Plumbagin against hepatoma studied in rats.

PMID- 8264574
TI  - Phosphorylation of synthetic acidic peptides by casein kinase II: evidence for
      competition with phosphorylation of proteins involved in transcription.
AB  - Phosphorylation of several synthetic acidic peptides by biochemically isolated
      casein kinase II (CKII) and by cellular and nuclear extracts containing CKII-like
      activity has been investigated. Especially the synthetic peptide pyroGlu-Asp-Asp
      Ser-Asp-Glu-Glu-Asn comprising the carboxy-terminal acidic hepta-peptide of the
      largest subunit of RNA polymerase II was found to serve as an excellent substrate
      for purified CKII. Moreover, this peptide reduces the rate of 'in vitro' ATP
      dependent stimulation of DNA transcription induced by the proteins in the
      extracts. Since the peptide itself is also significantly phosphorylated in such
      assays, it is supposed that it serves as a competitive substrate for the
      phosphorylation of proteins in the extracts whose phosphorylation seems to be a
      prerequisite for their activity in the transcription process. This points to the
      involvement of CKII and substrate(s) of CKII in the process of transcription.

PMID- 8264575
TI  - Effect of lacidipine on ischaemic and reperfused isolated rabbit hearts.
AB  - Lacidipine is a new developed dihydropyridine calcium-antagonist, showing a slow
      onset and long lasting-selective activity. To assess whether the administration
      of lacidipine protects the myocardium in a dose-dependent manner against
      ischaemia and reperfusion, isolated rabbit heart were infused with three
      different concentrations of lacidipine: 10(-10); 10(-9); 10(-8) M. Diastolic and
      developed pressures were monitored; coronary effluent was collected and assayed
      for CPK activity and for noradrenaline concentration; mitochondria were harvested
      and assayed for respiratory activity, ATP production and calcium content and
      tissue concentration of ATP, creatine phosphate (CP) and calcium were determined.
      Occurrence of oxidative stress during ischaemia and reperfusion was also
      monitored in terms of tissue content and release of reduced (GSH) and oxidized
      (GSSG) glutathione. Treatment with lacidipine at 10(-10) and 10(-9) M had no
      effects on the hearts when perfused under aerobic condition, whilst the higher
      dose reduced developed pressure of 36%. The ischaemic-induced deterioration of
      mitochondrial function was attenuated. On reperfusion treated hearts recovered
      better than the untreated hearts with respect to left ventricular performance,
      replenishment of ATP and CP stores and mitochondrial function. The reperfusion
      induced tissue and mitochondrial calcium overload, release of CPK and of
      noradrenaline and oxidative stress were also significantly reduced. The effects
      of lacidipine were dose-dependent. The lower concentration (10(-10) M) failed to
      modify ischaemic and reperfusion damage. The dose of 10(-9) M was
      cardioprotective, but the best effect was found at 10(-8) M. It is concluded that
      lacidipine infusion provides a dose dependent protection of the heart against
      ischaemia and reperfusion. Because this protection occurred also at 10(-9) M, in
      the absence of negative inotropic effect during normoxia and of a coronary
      dilatory effect during ischaemia, it cannot be attributed to an energy sparing
      effect or to improvement of oxygen delivery. From our data we can envisage two
      other major mechanism: -1) membrane protection -2) reduction of oxygen toxicity.
      The ATP sparing effect occurring at 10(-8) M is likely to be responsable for the
      further protection.

PMID- 8264576
TI  - Coexistence of two chromatin structures in sperm nuclei of the bivalve mollusc
      Protothaca thaca.
AB  - The chromatin of the spermatozoa from the bivalve mollusc Protothaca thaca, has a
      peculiar composition in which coexist core histones with sperm-specific proteins
      H1 and Pt1, the latter being a protein exhibiting features intermediate between
      histones and protamines. In this paper, we report an analysis of chromatin
      organization using micrococcal nuclease digestion, salt fractionation of soluble
      chromatin derived from nuclease digestion and crosslinking experiments. The
      results obtained indicate that it is possible to obtain two types of chromatin,
      one which is soluble, more accessible to micrococcal nuclease action and which
      does not contain Pt1, and another insoluble type, more resistant to micrococcal
      nuclease and enriched in protein Pt1. The crosslinking experiments show that the
      protein Pt1 interacts with itself and with core histones but not with sperm
      specific H1. These results have led us to propose a special structural
      arrangement for this chromatin. Based in the data reported here we propose the
      coexistence in the genome of P. thaca of two interspersed chromatin domains, one
      nucleosomal and the other nonnucleosomal containing protein Pt1.

PMID- 8264577
TI  - Receptor tyrosine phosphatase R-PTP-kappa mediates homophilic binding.
AB  - Receptor tyrosine phosphatases (R-PTPases) feature PTPase domains in the context
      of a receptor-like transmembrane topology. The R-PTPase R-PTP-kappa displays an
      extracellular domain composed of fibronectin type III motifs, a single
      immunoglobulin domain, as well as a recently defined MAM domain (Y.-P. Jiang, H.
      Wang, P. D'Eustachio, J.M. Musacchio, J. Schlessinger, and J. Sap, Mol. Cell.
      Biol. 13:2942-2951, 1993). We report here that R-PTP-kappa can mediate homophilic
      intercellular interaction. Inducible expression of the R-PTP-kappa protein in
      heterologous cells results in formation of stable cellular aggregates strictly
      consisting of R-PTP-kappa-expressing cells. Moreover, the purified extracellular
      domain of R-PTP-kappa functions as a substrate for adhesion by cells expressing R
      PTP-kappa and induces aggregation of coated synthetic beads. R-PTP-kappa-mediated
      intercellular adhesion does not require PTPase activity or posttranslational
      proteolytic cleavage of the R-PTP-kappa protein and is calcium independent. The
      results suggest that R-PTPases may provide a link between cell-cell contact and
      cellular signaling events involving tyrosine phosphorylation.

PMID- 8264578
TI  - Four distinct and unusual linker proteins in a mitotically dividing nucleus are
      derived from a 71-kilodalton polyprotein, lack p34cdc2 sites, and contain protein
      kinase A sites.
AB  - Tetrahymena thermophila micronuclei contain four linker-associated proteins,
      alpha, beta, gamma, and delta. Synthetic oligonucleotides based on N-terminal
      protein sequences of beta and gamma were used to clone the micronuclear linker
      histone (MLH) gene. The MLH gene is single copy and is transcribed into a 2.4-kb
      message encoding all four linker-associated proteins. The message is translated
      into a polypeptide (Mic LH) that is processed at the sequence decreases RTK to
      give proteins whose amino acid sequences differ markedly from each other, from
      the sequence of macronuclear H1, and from sequences of typical H1s of other
      organisms. This represents the first example of multiple chromatin proteins
      derived from a single polyprotein. The delta protein consists largely of two high
      mobility-group (HMG) boxes. An evolutionary analysis of HMG boxes indicates that
      the delta HMG boxes are similar to the HMG boxes of tsHMG, a protein that appears
      in elongating mouse spermatids when they condense and cease transcription,
      suggesting that delta could play a similar role in the micronucleus. The
      micronucleus divides mitotically, while the macronucleus divides amitotically.
      Surprisingly, macronuclear H1 but not Mic LH contains sequences resembling
      p34cdc2 kinase phosphorylation sites, while each of the Mic LH-derived proteins
      contains a typical protein kinase A phosphorylation site in its carboxy terminus.

PMID- 8264579
TI  - Isolation and characterization of a Saccharomyces cerevisiae peptide transport
      gene.
AB  - We have cloned and characterized a Saccharomyces cerevisiae peptide transport
      gene (PTR2) isolated from a genomic DNA library by directly selecting for
      functional complementation of a peptide transport-deficient mutant. Deletion and
      frameshift mutageneses were used to localize the complementing activity to a 3.1
      kbp region on the transforming plasmid. DNA sequencing of the complementing
      region identified an open reading frame spanning 1,803 bp. The deduced amino acid
      sequence predicts a hydrophobic peptide consisting of 601 amino acids, having a
      molecular mass of 68.1 kDa, composed in part of 12 hydrophobic segments, and
      sharing significant similarities with a nitrate transport protein encoded by the
      CHL1 gene of Arabidopsis thaliana. Northern (RNA) hybridization experiments
      demonstrated a single transcript that was 1.8 kb in length and that was
      transiently induced by the addition of L-leucine to the growth medium. The PTR2
      gene was localized to the right arm of chromosome XI by contour-clamped
      homogeneous electric field gel chromosome blotting and by hybridization to known
      chromosome XI lambda phage clones of S. cerevisiae DNA. PTR2 was tightly linked
      to the UBI2 gene, with the coding sequences being separated by a 466-bp region
      and oriented so that the genes were transcribed convergently. A chromosomal
      disruption of the PTR2 gene in a haploid strain was not lethal under standard
      growth conditions. The cloning of PTR2 represents the first example of the
      molecular genetic characterization of a eucaryotic peptide transport gene.

PMID- 8264580
TI  - DNA sequence requirements for transcriptional initiator activity in mammalian
      cells.
AB  - A transcriptional initiator (Inr) for mammalian RNA polymerase II can be defined
      as a DNA sequence element that overlaps a transcription start site and is
      sufficient for (i) determining the start site location in a promoter that lacks a
      TATA box and (ii) enhancing the strength of a promoter that contains a TATA box.
      We have prepared synthetic promoters containing random nucleotides downstream of
      Sp1 binding sites to determine the range of DNA sequences that convey Inr
      activity. Numerous sequences behaved as functional Inrs in an in vitro
      transcription assay, but the Inr activities varied dramatically. An examination
      of the functional elements revealed loose but consistent sequence requirements,
      with the approximate consensus sequence Py Py A+1 N T/A Py Py. Most importantly,
      almost every functional Inr that has been described fits into the consensus
      sequence that we have defined. Although several proteins have been reported to
      bind to specific Inrs, manipulation of those elements failed to correlate protein
      binding with Inr activity. The simplest model to explain these results is that
      all or most Inrs are recognized by a universal binding protein, similar to the
      functional recognition of all TATA sequences by the same TATA-binding protein.
      The previously reported proteins that bind near specific Inr elements may augment
      the strength of an Inr or may impart transcriptional regulation through an Inr.

PMID- 8264581
TI  - The nuclear factor YY1 participates in repression of the beta-casein gene
      promoter in mammary epithelial cells and is counteracted by mammary gland factor
      during lactogenic hormone induction.
AB  - Expression of the beta-casein milk protein gene in the mammary epithelial cell
      line HC11 is primarily regulated at the transcriptional level. A 338-bp segment
      of promoter sequence 5' of the transcription start site is sufficient to confer
      inducibility by the lactogenic hormones insulin, glucocorticoid hormone, and
      prolactin. Positively and negatively acting promoter elements and specific DNA
      binding proteins have been identified. The binding of the mammary gland factor
      MGF to a site between -80 and -100 is indispensable for hormonal induction of
      transcription. Binding of MGF activity to DNA is greatly enhanced by the action
      of the lactogenic hormones. Repression of transcription in the uninduced state is
      mediated by a promoter element located adjacent to the MGF binding site at
      positions -110 to -150. This repressor element consists of two interacting
      protein binding sites. A nuclear factor that binds specifically to the proximal
      site between positions -110 and -120 has been characterized and found to be
      identical with the nuclear factor YY1 (delta, NF-E1). YY1 does not bind to the
      distal site. The simultaneous mutation in the proximal and the distal sites
      results in high, hormone-independent transcription. This finding suggests that
      YY1 plays a functional role in the repression and acts in conjunction with a
      second DNA binding protein. Comparison of YY1 DNA binding activity in uninduced
      and hormone-induced cells showed that relief of repression is not mediated by
      changes in the concentration or binding affinity of YY1. Infection of HC11 cells
      with a YY1-expressing recombinant retrovirus resulted in overexpression of YY1
      but did not suppress hormonal induction. The addition of purified MGF decreased
      YY1 binding to its DNA recognition site in vitro. This finding indicates that MGF
      regulates the DNA binding activity of YY1 and thereby may cause the relief of
      transcriptional repression.

PMID- 8264582
TI  - Multiple regions within the cytoplasmic domains of the leukemia inhibitory factor
      receptor and gp130 cooperate in signal transduction in hepatic and neuronal
      cells.
AB  - The receptor for leukemia inhibitory factor (LIFR), in combination with the
      signal-transducing subunit for interleukin-6-type cytokine receptors, gp130, and
      LIF, activates transcription of acute-phase plasma protein genes in human and rat
      hepatoma cells and the vasoactive intestinal peptide gene in a human
      neuroblastoma cell line. To identify the regions within the cytoplasmic domain of
      LIFR that initiate signal transduction independently of gp130, we constructed a
      chimeric receptor by linking the extracellular domain of the granulocyte colony
      stimulating factor receptor (G-CSFR) to the transmembrane and cytoplasmic domain
      of human LIFR. The function of the chimeric receptor protein in transcriptional
      activation was assessed by G-CSF-mediated stimulation of cotransfected cytokine
      responsive reporter gene constructs in hepatoma and neuroblastoma cells. By using
      the full-length cytoplasmic domain and mutants with progressive carboxy-terminal
      deletions, internal deletions, or point mutations, we identified the first 150
      amino acid residues of LIFR as the minimal region necessary for signaling. The
      signaling reaction appears to involve a cooperativity between the first 70-amino
      acid region containing the two sequence motifs conserved among hematopoietin
      receptors (box 1 and box 2) and a critical sequence between residues 141 and 150
      (box 3). Analogous analyses of the cytoplasmic domains of G-CSFR and gp130
      indicated similar arrangements of functional domains in these receptor subunits
      and the requirement of a box 3-related motif for signaling.

PMID- 8264584
TI  - Characterization of DNA end joining in a mammalian cell nuclear extract: junction
      formation is accompanied by nucleotide loss, which is limited and uniform but not
      site specific.
AB  - Mammalian cells have a marked capacity to repair double-strand breaks in DNA, but
      the molecular and biochemical mechanisms underlying this process are largely
      unknown. A previous report has described an activity from mammalian cell nuclei
      that is capable of multimerizing blunt-ended DNA substrates (R. Fishel, M.K.
      Derbyshire, S.P. Moore, and C.S.H. Young, Biochimie 73:257-267, 1991). In this
      report, we show that nuclear extracts from HeLa cells contain activities which
      preferentially join linear plasmid substrates in either a head-to-head or tail-to
      tail configuration, that the joining reaction is covalent, and that the joining
      is accompanied by loss of sequence at the junction. Sequencing revealed that
      there was a loss of a uniform number of nucleotides from junctions formed from
      any one type of substrate. The loss was not determined by any simple site
      specific mechanism, but the number of nucleotides lost was affected by the
      precise terminal sequence. There was no major effect on the efficiency or outcome
      of the joining reaction with substrates containing blunt ends or 3' or 5'
      protruding ends. Using a pair of plasmid molecules with distinguishable
      restriction enzyme sites, we also observed that blunt-ended DNA substrates could
      join with those containing protruding 3' ends. As with the junctions formed
      between molecules with identical ends, there was uniform loss of nucleotides.
      Taken together, the data are consistent with two models for the joining reaction
      in which molecules are aligned either throughout most of their length or by using
      small sequence homologies located toward their ends. Although either model can
      explain the preferential formation of head-to-head and tail-to-tail products, the
      latter predicts the precise lossof nucleotides observed. These activities are
      found in all cell lines examined so far and most likely represent an important
      repair activity of the mammalian cell.

PMID- 8264583
TI  - Nonhomologous recombination in human cells.
AB  - Nonhomologous recombination (NHR) is a major pathway for the repair of
      chromosomal double-strand breaks in the DNA of somatic cells. In this study, a
      comparison was made between the nonhomologous end joining of transfected
      adenovirus DNA fragments in vivo and the ability of purified human proteins to
      catalyze nonhomologous end joining in vitro. Adenovirus DNA fragments were shown
      to be efficiently joined in human cells regardless of the structure of the ends.
      Sequence analysis of these junctions revealed that the two participating ends
      frequently lost nucleotides from the 3' strands at the site of the joint. To
      examine the biochemical basis of the end joining, nuclear extracts were prepared
      from a wide variety of mammalian cell lines and tested for their ability to join
      test plasmid substrates. Efficient ligation of the linear substrate DNA was
      observed, the in vitro products being similar to the in vivo products with
      respect to the loss of 3' nucleotides at the junction. Substantial purification
      of the end-joining activity was carried out with the human immature T-cell-line
      HPB-ALL. The protein preparation was found to join all types of linear DNA
      substrates containing heterologous ends with closely equivalent efficiencies. The
      in vitro system for end joining does not appear to contain any of the three known
      DNA ligases, on the basis of a number of criteria, and has been termed the NHR
      ligase. The enriched activity resides in a high-molecular-weight recombination
      complex that appears to include and require the human homologous pairing protein
      HPP-1 as well as the NHR ligase. Characterization of the product molecules of the
      NHR ligase reaction suggests that they are linear oligomers of the monomer
      substrate joined nonrandomly head-to-head and/or tail-to-tail. The joined ends of
      the products were found to be modified by a 3' exonuclease prior to ligation, and
      no circular DNA molecules were detected. These types of products are similar to
      those required for the breakage-fusion-bridge cycle, a major NHR pathway for
      chromosome double-strand break repair.

PMID- 8264585
TI  - Fibroblast growth factor receptors have different signaling and mitogenic
      potentials.
AB  - Fibroblast growth factor (FGF) receptors (FGFRs) are structurally related
      receptor protein tyrosine kinases encoded by four distinct genes. Activation of
      FGFR-1, -2, and -3 by FGFs induces mitogenic responses in various cell types, but
      the mitogenic potential of FGFR-4 has not been previously explored. We have
      compared the properties of BaF3 murine lymphoid cells and L6 rat myoblast cells
      engineered to express FGFR-1 or FGFR-4. Acidic FGF binds with high affinity to
      and elicits tyrosine phosphorylation of FGFR-1 or FGFR-4 receptors displayed on
      BaF3 cells, but only FGFR-1 activation leads to cell survival and growth. FGFR-4
      activation also fails to elicit detectable signals characteristic of the FGFR-1
      response: tyrosine phosphorylation of SHC and extracellular signal-related kinase
      (ERK) proteins and induction of fos and tis11 RNA expression. The only detected
      response to FGFR-4 activation was weak phosphorylation of phospholipase C gamma.
      A chimeric receptor containing the extracellular domain of FGFR-4 and the
      intracellular domain of FGFR-1 confers FGF-dependent growth upon transfected BaF3
      cells, demonstrating that the intracellular domains of the receptors dictate
      their functional capacity. Activation of FGFR-1 in transfected L6 myoblasts
      induced far stronger phosphorylation of phospholipase C gamma, SHC, and ERK
      proteins than could activation of FGFR-4 in L6 cells, and only FGFR-1 activation
      induced tyrosine phosphorylation of a characteristic 80-kD protein. Hence, the
      signaling and biological responses elicited by different FGF receptors
      substantially differ.

PMID- 8264586
TI  - Heat shock factor can activate transcription while bound to nucleosomal DNA in
      Saccharomyces cerevisiae.
AB  - After each round of replication, new transcription initiation complexes must
      assemble on promoter DNA. This process may compete with packaging of the same
      promoter sequences into nucleosomes. To elucidate interactions between regulatory
      transcription factors and nucleosomes on newly replicated DNA, we asked whether
      heat shock factor (HSF) could be made to bind to nucleosomal DNA in vivo. A heat
      shock element (HSE) was embedded at either of two different sites within a DNA
      segment that directs the formation of a stable, positioned nucleosome. The
      resulting DNA segments were coupled to a reporter gene and transfected into the
      yeast Saccharomyces cerevisiae. Transcription from these two plasmid
      constructions after induction by heat shock was similar in amount to that from a
      control plasmid in which HSF binds to nucleosome-free DNA. High-resolution
      genomic footprint mapping of DNase I and micrococcal nuclease cleavage sites
      indicated that the HSE in these two plasmids was, nevertheless, packaged in a
      nucleosome. The inclusion of HSE sequences within (but relatively close to the
      edge of) the nucleosome did not alter the position of the nucleosome which formed
      with the parental DNA fragment. Genomic footprint analyses also suggested that
      the HSE-containing nucleosome was unchanged by the induction of transcription.
      Quantitative comparisons with control plasmids ruled out the possibility that HSF
      was bound only to a small fraction of molecules that might have escaped
      nucleosome assembly. Analysis of the helical orientation of HSE DNA in the
      nucleosome indicated that HSF contacted DNA residues that faced outward from the
      histone octamer. We discuss the significance of these results with regard to the
      role of nucleosomes in inhibiting transcription and the normal occurrence of
      nucleosome-free regions in promoters.

PMID- 8264587
TI  - Attenuation of ribosomal protein S6 phosphatase activity in chicken embryo
      fibroblasts transformed by Rous sarcoma virus.
AB  - In chicken embryo fibroblasts, phosphorylation of the 40S ribosomal protein S6
      increases during G1 but returns to basal level by mitosis. In contrast, in Rous
      sarcoma virus (RSV)-transformed fibroblasts, S6 remains highly phosphorylated
      throughout mitosis. This study investigated the mechanism by which RSV alters the
      pattern of S6 phosphorylation. Pulse-chase experiments demonstrate that phosphate
      turnover in S6 is rapid in normal cells and in cells infected with an RSV
      transformation-defective virus. In contrast, phosphate turnover in S6 is severely
      reduced in cells infected with temperature-sensitive RSV at a temperature
      permissive for transformation, indicating a diminished S6 phosphatase activity.
      Fractionation of cell lysates by DEAE chromatography showed an almost threefold
      lower S6 phosphatase activity in RSV-transformed versus normal cells. The S6
      phosphatase was sensitive to inhibitor 2 and specifically recognized by an
      antibody to type 1 phosphatase (PP1). The S6 phosphatase activity recovered by
      immunoprecipitation of PP1 was threefold lower in transformed cells, but the
      steady-state level of expression and the rate of synthesis of PP1 were not
      altered by oncogenic transformation. Together, the results show that
      transformation by RSV reduced the S6-PP1 activity.

PMID- 8264588
TI  - Identification of a thymidylate synthase ribonucleoprotein complex in human colon
      cancer cells.
AB  - Translation of thymidylate synthase (TS) mRNA is controlled by its own protein
      product, TS, in an autoregulatory manner. Direct binding of TS protein to two
      different cis-acting elements on the TS mRNA is associated with this
      translational regulation. In this study, an immunoprecipitation-reverse
      transcription-PCR technique was used to identify a TS ribonucleoprotein (RNP)
      complex in cultured human colon cancer cells. Using antibodies specific for TS
      protein, we show that TS is complexed in vivo with its own TS RNA. Furthermore,
      evidence demonstrating a direct interaction between the mRNA of the nuclear
      oncogene c-myc and TS protein is presented.

PMID- 8264590
TI  - Yeast intragenic transcriptional control: activation and repression sites within
      the coding region of the Saccharomyces cerevisiae LPD1 gene.
AB  - Though widely recognized in higher eukaryotes, the regulation of Saccharomyces
      cerevisiae genes transcribed by RNA polymerase II by proteins that bind within
      the coding sequence remains largely speculative. We have shown for the LPD1 gene,
      encoding lipoamide dehydrogenase, that the coding sequence between +13 and +469
      activated gene expression of an LPD1::lacZ fusion by up to sixfold in the
      presence of the upstream promoter. This downstream region, inserted upstream of a
      promoterless CYC1::lacZ fusion, activated gene expression in a carbon source
      dependent manner by a factor of 15 to 111, independent of orientation. Deletion
      and mutational analysis identified two downstream activation sites (DAS1 and
      DAS2) and two downstream repressor sites (DRS1 and DRS2) that influence the rate
      of LPD1 transcription rather than mRNA degradation or translation. Activation
      from the DAS1 region (positions +137 to +191), encompassing a CDEI-like element,
      is twofold under derepressive conditions. Activation from DAS2 (+291 to +296), a
      CRE-like motif, is 12-fold for both repressed and derepressed states. DRS1, a
      pair of adjacent and opposing ABF1 sites (+288 to +313), is responsible for a 1.3
      to 2-fold repression of transcription, depending on the carbon source. DRS1
      requires the concerted action of DRS2 (a RAP1 motif at position +406) for
      repression of transcription only when the gene is induced. Gel mobility shift
      analysis and in vitro footprinting have shown that proteins bind in vitro to
      these downstream elements.

PMID- 8264589
TI  - Addition of lipid substituents of mammalian protein glycosylphosphoinositol
      anchors.
AB  - A single metabolic path leading to synthesis of ether lipids is known in animal
      cells, the major products of which are plasmalogens. To learn whether this
      peroxisomal path is also responsible for the synthesis of base-resistant lipid
      components of glycosylphosphoinositol (GPI)-anchored membrane proteins, we have
      investigated the structure of anchor precursor mannolipids both in wild-type
      cells (CHO-K1 and a macrophage-like line, RAW 264.7) and in two corresponding
      mutant cells in which ether lipid biosynthesis is severely impaired. We observe
      that the precursor mannolipids of both the wild-type and mutant cells do not
      include alkylglycerol. Nevertheless, both wild-type and mutant cells express cell
      surface GPI-anchored placental alkaline phosphatase (AP) which includes alkali
      resistant hydrophobic chains in its anchor moiety. Thus, (i) in normal AP GPI
      anchor synthesis, any ether-linked substituents must be added either immediately
      before, during, or after anchor addition to AP, and (ii) the classical
      peroxisomal path for ether lipid synthesis appears not to contribute to the
      synthesis of GPI anchors.

PMID- 8264591
TI  - The sua8 suppressors of Saccharomyces cerevisiae encode replacements of conserved
      residues within the largest subunit of RNA polymerase II and affect transcription
      start site selection similarly to sua7 (TFIIB) mutations.
AB  - Mutations in the Saccharomyces cerevisiae sua8 gene were found to be suppressors
      of an aberrant ATG translation initiation codon in the leader region of the cyc1
      gene. Analysis of cyc1 transcripts from sua8 mutants revealed that suppression is
      a consequence of diminished transcription initiation at the normal start sites in
      favor of initiation at downstream sites, including a site between the aberrant
      and normal ATG start codons. This effect is not cyc1 gene specific since
      initiation at other genes, including ADH1, CYC7, and HIS4, was similarly
      affected, although initiation at HIS3 and SPT15 was unaffected. The SUA8 gene was
      cloned and partially sequenced, revealing identity to RPB1, which encodes the
      largest subunit of RNA polymerase II. The sua8 suppressors are the result of
      single amino acid replacements of highly conserved residues. Three replacements
      were found either within or immediately preceding homology block D, and a fourth
      was found adjacent to homology block H, indicating that these regions play a role
      in defining start sites in vivo. Nearly identical effects on start site selection
      were observed for sua7 suppressors, which encode altered forms of TFIIB.
      Synthetic lethality was associated with double sua7 sua8 suppressor mutations,
      and recessive sua7 mutants failed to fully complement recessive sua8 mutants in
      heterozygous diploids (nonallelic noncomplementation). These data indicate that
      the largest subunit of RNA polymerase II and TFIIB are important determinants of
      transcription start site selection in S. cerevisiae and suggest that this
      function might be conferred by interaction between these two proteins.

PMID- 8264592
TI  - Functional analysis of mouse Hoxa-7 in Saccharomyces cerevisiae: sequences
      outside the homeodomain base contact zone influence binding and activation.
AB  - The murine developmental control gene product, Hoxa-7, was shown to function as a
      DNA-binding transactivator in Saccharomyces cerevisiae. The importance of the
      ATTA core, the preference for antp class flanking nucleotides, the importance of
      Asn-51 of the homeodomain (HD), and the synergism of multiple binding sites all
      reflect properties that have previously been described for HOM or Hox proteins in
      tissue culture systems. A comparison of contact positions among genes of paralog
      groups and classes of mammalian HDs points to a lack of diversity in positions
      that make base contact, suggesting that besides the combination of HD amino acid
      base pair contacts, another means of recognizing differences between targets must
      exist if Hox genes select different targets. The HD of antennapedia is identical
      to the Hoxa-7 HD. The interaction of Hoxa-7 with the exact sequence used in the
      nuclear magnetic resonance three-dimensional structural analysis on the
      antennapedia HD was studied. Hoxa-7 binding and transactivation was influenced by
      sequences outside of the known base contact zone of this site. We conclude that
      Hoxa-7 protein has a second means to interact with DNA or/and that the sequences
      flanking the base contact zone influence HD interactions by distorting DNA within
      the contact zone (base or backbone). This result is discussed in terms of DNA
      flexure and two modes of transcription used in S. cerevisiae.

PMID- 8264593
TI  - CDC44: a putative nucleotide-binding protein required for cell cycle progression
      that has homology to subunits of replication factor C.
AB  - To investigate the means by which a cell regulates the progression of the mitotic
      cell cycle, we characterized cdc44, a mutation that causes Saccharomyces
      cerevisiae cells to arrest before mitosis. CDC44 encodes a 96-kDa basic protein
      with significant homology to a human protein that binds DNA (PO-GA) and to three
      subunits of human replication factor C (also called activator 1). The hypothesis
      that Cdc44p is involved in DNA metabolism is supported by the observations that
      (i) levels of mitotic recombination suggest elevated rates of DNA damage in cdc44
      mutants and (ii) the cell cycle arrest observed in cdc44 mutants is alleviated by
      the DNA damage checkpoint mutations rad9, mec1, and mec2. The predicted amino
      acid sequence of Cdc44p contains GTPase consensus sites, and mutations in these
      regions cause a conditional cell cycle arrest. Taken together, these observations
      suggest that the essential CDC44 gene may encode the large subunit of yeast
      replication factor C.

PMID- 8264594
TI  - Fos and Jun repress transcription activation by NF-IL6 through association at the
      basic zipper region.
AB  - NF-IL6 and AP-1 family transcription factors are coordinately induced by
      interleukin-6 (IL-6) in a cell-type-specific manner, suggesting that they mediate
      IL-6 signals in the nucleus. We show that the basic leucine zipper (bZIP) region
      of NF-IL6 mediates a direct association with the bZIP regions of Fos and Jun in
      vitro. This interaction does not depend on the presence of their cognate
      recognition DNA elements or the posttranslational modification of either partner.
      NF-IL6 homodimers can bind to both NF-IL6 and AP-1 sites, whereas Fos and Jun
      cannot bind to most NF-IL6 sites. Cross-family association with Fos or with Jun
      alters the DNA binding specificity of NF-IL6 and reduced its binding to NF-IL6
      sites. NF-IL6 isoforms that differ in the site of translation initiation have
      distinct transcriptional activities. Activation of a reporter gene linked to the
      NF-IL6 site by NF-IL6 is repressed by Fos and by Jun in transient transfection
      assays. Thus, association with AP-1 results in repression of transcription
      activation by NF-IL6. The repression is NF-IL6 site dependent and may have a role
      in determining the promoter and cell type specificity in IL-6 signaling.

PMID- 8264595
TI  - Different agonist- and antagonist-induced conformational changes in retinoic acid
      receptors analyzed by protease mapping.
AB  - The pleiotropic effects of retinoic acid on cell differentiation and
      proliferation are mediated by two subfamilies of nuclear receptors, the retinoic
      acid receptors (RARs) and the retinoid X receptors (RXRs). Recently the synthetic
      retinoid Ro 41-5253 was identified as a selective RAR alpha antagonist. As
      demonstrated by gel retardation assays, Ro 41-5253 and two related new RAR alpha
      antagonists do not influence RAR alpha/RXR alpha heterodimerization and DNA
      binding. In a limited trypsin digestion assay, complexation of RAR alpha with
      retinoic acid or several other agonistic retinoids altered the degradation of the
      receptor such that a 30-kDa proteolytic fragment became resistant to proteolysis.
      This suggests a ligand-induced conformational change, which may be necessary for
      the interaction of the DNA-bound RAR alpha/RXR alpha heterodimer with other
      transcription factors. Our results demonstrate that antagonists compete with
      agonists for binding to RAR alpha and may induce a different structural
      alteration, suggested by the tryptic resistance of a shorter 25-kDa protein
      fragment in the digestion assay. This RAR alpha conformation seems to allow RAR
      alpha/RXR alpha binding to DNA but not the subsequent transactivation of target
      genes. Protease mapping with C-terminally truncated receptors revealed that the
      proposed conformational changes mainly occur in the DE regions of RAR alpha.
      Complexation of RAR beta, RAR gamma, and RXR alpha, as well as the vitamin D3
      receptor, with their natural ligands resulted in a similar resistance of
      fragments to proteolytic digestion. This could mean that ligand-induced
      conformational changes are a general feature in the hormonal activation of
      vitamin D3 and retinoid receptors.

PMID- 8264596
TI  - The transcription factor E2F-1 mediates the autoregulation of RB gene expression.
AB  - The retinoblastoma (RB) gene is the prototype tumor suppressor gene. Mutations in
      this gene are often associated with the occurrence of various tumors. Several
      mutations have been found in the promoter region of the gene, suggesting that
      inappropriate transcriptional regulation of the RB gene contributes to
      tumorigenesis. Sequence analysis of the RB promoter has revealed a potential E2F
      recognition site within a region critical for RB gene transcription. By using the
      cloned E2F-1 gene, here we report that (i) RB expression is negatively regulated
      by its own gene product, (ii) E2F-1 binds specifically to an E2F recognition
      sequence in the RB promoter and transactivates the RB promoter, (iii)
      overexpression of RB suppresses E2F-1-mediated stimulation of RB promoter
      activity, and (iv) the expression of the RB gene is paralleled by the expression
      of the E2F-1 gene during cell cycle progression. These results demonstrate that
      expression of RB is negatively autoregulated through E2F-1.

PMID- 8264597
TI  - Aberrant DNA repair and DNA replication due to an inherited enzymatic defect in
      human DNA ligase I.
AB  - Two missense mutations in different alleles of the DNA ligase I gene have been
      described in a patient (46BR) with immunodeficiencies and cellular
      hypersensitivity to DNA-damaging agents. One of the mutant alleles produces an
      inactive protein, while the other encodes an enzyme with some residual activity.
      A subline of identical phenotype that is homozygous (or hemizygous) for the
      mutant allele encoding this partially active enzyme has facilitated
      characterization of the enzymatic defect in 46BR. This subline retains only 3 to
      5% of normal DNA ligase I activity. The intermediates in the ligation reaction,
      DNA ligase I-AMP and nicked DNA-AMP, accumulate in vitro and in vivo. The defect
      of the 46BR enzyme lies primarily in conversion of nicked DNA-AMP into the final
      ligated DNA product. Assays of DNA repair in 46BR cell extracts and of DNA
      replication in permeabilized cells have clarified functional roles of DNA ligase
      I. The initial rate of ligation of Okazaki fragments during DNA replication is
      apparently normal in 46BR cells, but 25 to 30% of the fragments remain in low
      molecular-weight form for prolonged times. DNA base excision repair by 46BR cell
      extracts shows a delay in ligation and an anomalously long repair patch size that
      is reduced upon addition of purified normal DNA ligase I.

PMID- 8264598
TI  - Chromatin structure and transcriptional activity around the replication forks
      arrested at the 3' end of the yeast rRNA genes.
AB  - Replication intermediates containing forks arrested at the replication fork
      barrier near the 3' end of the yeast rRNA genes were analyzed at the chromatin
      level by using in vivo psoralen cross-linking as a probe for chromatin structure.
      These specific intermediates were purified from preparative two-dimensional
      agarose gels, and the extent of cross-linking in the different portions of the
      branched molecules was examined by electron microscopy and by using a psoralen
      gel retardation assay. The unreplicated section corresponding to the rRNA coding
      region upstream of the arrested forks appeared mostly heavily cross-linked,
      characteristic of transcriptionally active rRNA genes devoid of nucleosomes,
      whereas the replicated daughter strands representing newly synthesized spacer
      sequences showed a nucleosomal organization typical for bulk chromatin. The
      failure to detect replication forks arrested at the 3' end of inactive rRNA gene
      copies and the fact that most DNA encoding rRNA (rDNA) is replicated in the same
      direction as transcription suggest that replication forks seldom originate from
      origins of replication located immediately downstream of inactive genes.

PMID- 8264599
TI  - Nucleosome-mediated disruption of transcription factor-chromatin initiation
      complexes at the mouse mammary tumor virus long terminal repeat in vivo.
AB  - Glucocorticoid induction of mouse mammary tumor virus (MMTV) is short lived,
      returning to base levels within 24 h despite the continued presence of hormone.
      MMTV DNA sequences assembled as chromatin require hormone for binding by nuclear
      factor 1 (NF1) and octamer proteins (OCT). However, in the same cells, NF1 and
      OCT factors are bound to transiently introduced DNA in the absence of hormone. In
      contrast, recruitment of the TATA-binding protein and a novel DNA-binding
      protein, which we have designated FDT, for factor downstream of the TATA-binding
      protein, is hormone dependent for both stable and transient templates.
      Furthermore, transient DNA templates, but not nucleosomal templates, retain these
      transcription factors over the course of 24 h. This finding suggests that MMTV
      chromatin structure contributes to activation and cessation of transcription in
      vivo.

PMID- 8264600
TI  - Two upstream activation sequences control the expression of the XPR2 gene in the
      yeast Yarrowia lipolytica.
AB  - We have initiated a study of the promoter region of the alkaline extracellular
      protease gene (XPR2) from Yarrowia lipolytica to identify upstream sequences
      possibly involved in carbon, nitrogen, and peptone control of XPR2 expression.
      Deletion analysis showed that the TATA box and two major upstream activation
      sequences (UASs) were essential for promoter activity under conditions of
      repression or full induction. Within the distal UAS (UAS1), in vivo footprinting
      studies with dimethyl sulfate (DMS) identified two sequences similar to
      Saccharomyces cerevisiae GCN4 (-800 to -792)- and TUF/RAP1 (-790 to -778)-binding
      sites and two sequences which partially overlap a repeated sequence (-778 to -771
      and -720 to -713) similar to the CAR1 upstream repression sequence of S.
      cerevisiae. Oligonucleotides carrying the TUF/RAP1-like-binding site and adjacent
      downstream nucleotides restored full transcriptional activity of a UAS1-deleted
      promoter. Within the proximal UAS (UAS2), a directly repeated decameric sequence
      (-146 to -137 and -136 to -127) was protected against DMS in vivo. Sequences
      identical to the ABF1-binding site of S. cerevisiae (-121 to -109) or similar to
      the GCN4-binding site (-113 to -105) were not clearly protected from DMS in vivo.
      An oligomer (-150 to -106) carrying these three sequences, inserted into a UAS2
      deleted promoter, increased the transcriptional activity. The results from
      footprints under different physiological conditions suggested that protein
      binding to both UASs was constitutive. Deletion of both UASs greatly reduced XPR2
      expression without abolishing its regulation. Our results strongly suggest that
      these UASs are targets for transcriptional factors required for assisting
      specific regulatory proteins.

PMID- 8264601
TI  - Induction of Drosophila RNA polymerase III gene expression by the phorbol ester
      12-O-tetradecanoylphorbol-13-acetate (TPA) is mediated by transcription factor
      IIIB.
AB  - We have previously found that the phorbol ester 12-O-tetradecanoylphorbol-13
      acetate (TPA) induces specific transcription of tRNA and 5S RNA genes in
      Drosophila Schneider S-2 cells (M. Garber, S. Panchanathan, R. F. Fan, and D. L.
      Johnson, J. Biol. Chem. 266:20598-20601, 1991). Having derived cellular extracts
      from TPA-treated cells, that are capable of reproducing this stimulation in
      vitro, we have examined the mechanism for this regulatory event. Using conditions
      that limit reinitiation and produce single rounds of transcription from active
      gene complexes, we find that the number of functional transcription complexes is
      increased in extracts prepared from TPA-induced cells. We have analyzed the
      activities of the transcription factors TFIIIB and TFIIIC derived from extracts
      prepared from TPA-induced and noninduced cells. Examination of the relative
      activities of TFIIIC showed that both its ability to reconstitute transcription
      with TFIIIB and RNA polymerase III and its ability to stably bind to the DNA
      template are unchanged. However, the activity of TFIIIB derived from the TPA
      induced cells is substantially increased compared with that derived from the
      noninduced cells. The differences in TFIIIB activity account for the differences
      in the overall transcriptional activities observed in the unfractionated
      extracts. Western blot analysis of the TATA-binding protein subunit of TFIIIB
      revealed that there is an increase in the amount of this polypeptide present in
      the induced cell extracts and TFIIIB fraction. Together, these results indicate
      that the TPA response in Drosophila cells stimulates specific transcription of
      RNA polymerase III genes by increasing the activity of the limiting transcription
      component, TFIIIB, and thereby increasing the number of functional transcription
      complexes.

PMID- 8264602
TI  - A library of yeast genomic MCM1 binding sites contains genes involved in cell
      cycle control, cell wall and membrane structure, and metabolism.
AB  - The Saccharomyces cerevisiae MCM1 protein, which is essential for viability,
      participates in both transcription activation and repression as well as DNA
      replication. However, neither the full network of genes at which MCM1 acts nor
      whether MCM1 itself mediates a regulatory response is known. Thus far, sites of
      MCM1 action have been identified by chance during analysis of particular genes.
      To identify a more complete set of genes on which MCM1 acts, we isolated a
      library of yeast genomic sequences to which MCM1 binds and then identified known
      genes within this library. Fragments of genomic DNA, bound to bacterially
      expressed MCM1 protein, were collected on a nitrocellulose filter, cloned, and
      analyzed. This selected library contains a large number of genes. As expected, it
      is enriched for strong MCM1 binding sites and contains cell-type-specific genes
      known to require MCM1. In addition, it also includes sequences upstream (or near
      the 5' end) of a number of identified yeast genes that have not yet been shown to
      be controlled by MCM1. These include genes whose products are involved in (i) the
      control of cell cycle progression (CLN3, CLB2, and FAR1), (ii) synthesis and
      maintenance of cell wall or cell membrane structures (PMA1, PIS1, DIT1,2, and
      GFA1), (iii) cellular metabolism (PCK1, MET2, and CCP1), and (iv) production of a
      secreted glycoprotein which is heat shock inducible (HSP150). The previously
      unidentified MCM1 binding site in the essential PMA1 gene is required for
      expression of a PMA1:lacZ fusion gene, providing evidence that one site is
      functionally important. We speculate that MCM1 coordinates decisions about cell
      cycle progression with changes in cell wall integrity and metabolic activity. The
      presence in the library of three genes involved in cell cycle progression
      reinforces the idea that one of the functions of MCM1 is indeed analogous to that
      of the mammalian serum response factor.

PMID- 8264603
TI  - Dominant negative retinoid X receptor beta inhibits retinoic acid-responsive gene
      regulation in embryonal carcinoma cells.
AB  - Retinoid X receptors (RXRs) heterodimerize with multiple nuclear hormone
      receptors and are thought to exert pleiotropic functions. To address the role of
      RXRs in retinoic acid- (RA) mediated gene regulation, we designed a dominant
      negative RXR beta. This mutated receptor, termed DBD-, lacked the DNA binding
      domain but retained the ability to dimerize with partner receptors, resulting in
      formation of nonfunctional dimers. DBD- was transfected into P19 murine embryonal
      carcinoma (EC) cells, in which reporters containing the RA-responsive elements
      (RAREs) were activated by RA through the activity of endogenous RXR-RA receptor
      (RAR) heterodimers. We found that DBD- had a dominant negative activity on the
      RARE reporter activity in these cells. P19 clones stably expressing DBD- were
      established; these clones also failed to activate RARE-driven reporters in
      response to RA. Further, these cells were defective in RA-induced mRNA expression
      of Hox-1.3 and RAR beta, as well as in RA-induced down-regulation of Oct3 mRNA.
      Gel mobility shift assays demonstrated that RA treatment of control P19 cells
      induces RARE-binding activity, of which RXR beta is a major component. However,
      the RA-induced binding activity was greatly reduced in cells expressing DBD-. By
      genomic footprinting, we show that RA treatment induces in vivo occupancy of the
      RARE in the endogenous RAR beta gene in control P19 cells but that this occupancy
      is not observed with the DBD- cells. These data provide evidence that the
      dominant negative activity of DBD- is caused by the lack of receptor binding to
      target DNA. Finally, we show that in F9 EC cells expression of DBD- leads to
      inhibition of the growth arrest that accompanies RA-induced differentiation.
      Taken together, these results demonstrate that RXR beta and partner receptors
      play a central role in RA-mediated gene regulation and in the control of growth
      and differentiation in EC cells.

PMID- 8264604
TI  - The macrophage transcription factor PU.1 directs tissue-specific expression of
      the macrophage colony-stimulating factor receptor.
AB  - The macrophage colony-stimulating factor (M-CSF) receptor is expressed in a
      tissue-specific fashion from two distinct promoters in monocytes/macrophages and
      the placenta. In order to further understand the transcription factors which play
      a role in the commitment of multipotential progenitors to the monocyte/macrophage
      lineage, we have initiated an investigation of the factors which activate the M
      CSF receptor very early during the monocyte differentiation process. Here we
      demonstrate that the human monocytic M-CSF receptor promoter directs reporter
      gene activity in a tissue-specific fashion. Since one of the few transcription
      factors which have been implicated in the regulation of monocyte genes is the
      macrophage- and B-cell-specific PU.1 transcription factor, we investigated
      whether PU.1 binds and activates the M-CSF receptor promoter. Here we demonstrate
      that both in vitro-translated PU.1 and PU.1 from nuclear extracts bind to a
      specific site in the M-CSF receptor promoter just upstream from the major
      transcription initiation site. Mutations in this site which eliminate PU.1
      binding decrease M-CSF receptor promoter activity significantly in macrophage
      cell lines only. Furthermore, PU.1 transactivates the M-CSF receptor promoter in
      nonmacrophage cells. These results suggest that PU.1 plays a major role in
      macrophage gene regulation and development by directing the expression of a
      receptor for a key macrophage growth factor.

PMID- 8264605
TI  - Mice lacking c-fos have normal hematopoietic stem cells but exhibit altered B
      cell differentiation due to an impaired bone marrow environment.
AB  - Mice lacking c-fos develop severe osteopetrosis with deficiencies in bone
      remodeling and exhibit extramedullary hematopoiesis, thymic atrophy, and altered
      B-cell development. In this study, we have used these mice to characterize in
      detail the developmental potential of hematopoietic stem cells lacking c-fos and
      to analyze how the lymphoid differentiation is altered. In c-fos -/- mice, B-cell
      numbers are reduced in the spleen, lymph nodes, and the peripheral blood as a
      result of a marked reduction (> 90%) in the number of clonogenic B-cell
      precursors. In contrast, the number and lineage distribution of myeloid
      progenitor cells are not affected. The thymic defects observed in a large number
      of these mice correlate with their health status, suggesting that this may be an
      indirect effect of the c-fos mutation. In vitro differentiation and bone marrow
      reconstitution experiments demonstrated that hematopoietic stem cells lacking c
      fos can give rise to all mature myeloid as well as lymphoid cells, suggesting
      that the observed B lymphopenia in the mutant mice is due to an altered
      environment. Transplantation of wild-type bone marrow cells into newborn mutant
      mice resulted in the establishment of a bone marrow space and subsequent
      correction of the B-cell defect. These results demonstrate that hematopoietic
      stem cells lacking Fos have full developmental potential and that the observed
      defect in B-cell development is most likely due to the impaired bone marrow
      environment as a consequence of osteopetrosis.

PMID- 8264606
TI  - Preferential repair of UV damage in highly transcribed DNA diminishes UV-induced
      intrachromosomal recombination in mammalian cells.
AB  - The relationships among transcription, recombination, DNA damage, and repair in
      mammalian cells were investigated. We monitored the effects of transcription on
      UV-induced intrachromosomal recombination between neomycin repeats including a
      promoterless allele and an inducible heteroallele regulated by the mouse mammary
      tumor virus promoter. Although transcription and UV light separately stimulated
      recombination, increasing transcription levels reduced UV-induced recombination.
      Preferential repair of UV damage in transcribed strands was shown in highly
      transcribed DNA, suggesting that recombination is stimulated by unrepaired UV
      damage and that increased DNA repair in highly transcribed alleles removes
      recombinogenic lesions. This study indicates that the genetic consequences of DNA
      damage depend on transcriptional states and provides a basis for understanding
      tissue- and gene-specific responses to DNA-damaging agents.

PMID- 8264607
TI  - Mismatch repair of heteroduplex DNA intermediates of extrachromosomal
      recombination in mammalian cells.
AB  - Previous work indicated that extrachromosomal recombination in mammalian cells
      could be explained by the single-strand annealing (SSA) model. This model
      predicts that extrachromosomal recombination leads to nonconservative crossover
      products and that heteroduplex DNA (hDNA) is formed by annealing of complementary
      single strands. Mismatched bases in hDNA may subsequently be repaired to wild
      type or mutant sequences, or they may remain unrepaired and segregate following
      DNA replication. We describe a system to examine the formation and mismatch
      repair of hDNA in recombination intermediates. Our results are consistent with
      extrachromosomal recombination occurring via SSA and producing crossover
      recombinant products. As predicted by the SSA model, hDNA was present in double
      strand break-induced recombination intermediates. By placing either silent or
      frameshift mutations in the predicted hDNA region, we have shown that mismatches
      are efficiently repaired prior to DNA replication.

PMID- 8264608
TI  - Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of
      the bacterial mutL gene.
AB  - We have identified a new Saccharomyces cerevisiae gene, MLH1 (mutL homolog), that
      encodes a predicted protein product with sequence similarity to DNA mismatch
      repair proteins of bacteria (MutL and HexB) and S. cerevisiae yeast (PMS1).
      Disruption of the MLH1 gene results in elevated spontaneous mutation rates during
      vegetative growth as measured by forward mutation to canavanine resistance and
      reversion of the hom3-10 allele. Additionally, the mlh1 delta mutant displays a
      dramatic increase in the instability of simple sequence repeats, i.e., (GT)n (M.
      Strand, T. A. Prolla, R. M. Liskay, and T. D. Petes, Nature [London] 365:274-276,
      1993). Meiotic studies indicate that disruption of the MLH1 gene in diploid
      strains causes increased spore lethality, presumably due to the accumulation of
      recessive lethal mutations, and increased postmeiotic segregation at each of four
      loci, the latter being indicative of inefficient repair of heteroduplex DNA
      generated during genetic recombination. mlh1 delta mutants, which should
      represent the null phenotype, show the same mutator and meiotic phenotypes as
      isogenic pms1 delta mutants. Interestingly, mutator and meiotic phenotypes of the
      mlh1 delta pms1 delta double mutant are indistinguishable from those of the mlh1
      delta and pms1 delta single mutants. On the basis of our data, we suggest that in
      contrast to Escherichia coli, there are two MutL/HexB-like proteins in S.
      cerevisiae and that each is a required component of the same DNA mismatch repair
      pathway.

PMID- 8264609
TI  - Phosphatidylinositol 3-kinase activation is mediated by high-affinity
      interactions between distinct domains within the p110 and p85 subunits.
AB  - Domains of interaction between the p85 and p110 subunits of phosphatidylinositol
      3-kinase (PI 3-kinase) were studied with the yeast two-hybrid expression system.
      A gene fusion between the GAL4 transactivation domain and p85 activated
      transcription from a GAL1-lacZ reporter gene when complemented with a gene fusion
      between the GAL4 DNA binding domain and p110. To define subdomains responsible
      for this interaction, a series of p85 deletion mutants were analyzed. A 192-amino
      acid inter-SH2 (IS) fragment (residues 429 to 621) was the smallest determinant
      identified that specifically associated with p110. In analogous experiments, the
      subdomain within p110 responsible for interaction with p85 was localized to an
      EcoRI fragment encoding the amino-terminal 127 residues. Expression of these two
      subdomains [p85(IS) with p110RI] resulted in 100-fold greater reporter activity
      than that obtained with full-length p85 and p110. Although the p85(IS) domain
      conferred a strong interaction with the p110 catalytic subunit, this region was
      not sufficient to impart phosphotyrosine peptide stimulation of PI 3-kinase
      activity. In contrast, coexpression of the p110 subunit with full-length p85 or
      with constructs containing the IS sequences flanked by both SH2 domains of p85
      [p85(n/cSH2)] or either of the individual SH2 domains [p85(nSH2+IS) or
      p85(IS+cSH2)] resulted in PI 3-kinase activity that was activated by a
      phosphotyrosine peptide. These data suggest that phosphotyrosine peptide binding
      to either SH2 domain generates an intramolecular signal propagated through the IS
      region to allosterically activate p110.

PMID- 8264610
TI  - Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant
      distinguishes passive pore formation and active cell suicide mechanisms.
AB  - The role of the target cell in its own death mediated by cytotoxic T lymphocytes
      (CTL) has been controversial. The ability of the pore-forming granule components
      of CTL to induce target cell death directly has been taken to suggest an
      essentially passive role for the target. This view of CTL-mediated killing
      ascribes to the target the single role of providing an antigenic stimulus to the
      CTL; this signal results in the vectoral degranulation and secretion of pore
      forming elements onto the target. On the other hand, by a number of criteria,
      target cell death triggered by CTL appears fundamentally different from death
      resulting from membrane damage and osmotic lysis. CTL-triggered target cell death
      involves primary internal lesions of the target cell that reflect a physiological
      cell death process. Orderly nuclear disintegration, including lamin
      phosphorylation and solubilization, chromatin condensation, and genome digestion,
      are among the earliest events, preceding the loss of plasma membrane integrity.
      We have tested directly the involvement of the target cell in its own death by
      examining whether we could isolate mutants of target cells that have retained the
      ability to be recognized by and provide an antigenic stimulus to CTL while having
      lost the capacity to respond by dying. Here, we describe one such mutant, BW87.
      We have used this CTL-resistant mutant to analyze the mechanisms of CTL-triggered
      target cell death under a variety of conditions. The identification of a mutable
      target cell element essential for the cell death response to CTL provides genetic
      evidence that target cell death reflects an active cell suicide process similar
      to other physiological cell deaths.

PMID- 8264611
TI  - Human adenovirus encodes two proteins which have opposite effects on accumulation
      of alternatively spliced mRNAs.
AB  - All mRNAs expressed from the adenovirus major late transcription unit have a
      common, 201-nucleotide-long 5' leader sequence, which consists of three short
      exons (the tripartite leader). This leader has two variants, either with or
      without the i-leader exon, which, when present, is spliced between the second and
      the third exons of the tripartite leader. Previous studies have shown that
      adenovirus early region 4 (E4) encodes two proteins, E4 open reading frame 3 (E4
      ORF3) and E4-ORF6, which are required for efficient expression of mRNAs from the
      major late transcription unit. These two E4 proteins appear to have redundant
      activities, and expression of one has been shown to be sufficient for efficient
      major late mRNA accumulation during a lytic virus infection. In this report, we
      provide evidence that E4-ORF3 and E4-ORF6 both regulate major late mRNA
      accumulation by stimulating constitutive splicing. Moreover, we show that the two
      proteins have different effects on accumulation of alternatively spliced
      tripartite leader exons. In a DNA transfection assay, E4-ORF3 was shown to
      facilitate i-leader exon inclusion, while E4-ORF6 preferentially favored i-leader
      exon skipping. In addition, E4-ORF3 and E4-ORF6 had the same effects on
      accumulation of alternatively spliced chimeric beta-globin transcripts. This
      finding suggests that the activities of the two proteins may be of more general
      relevance and not restricted to splicing of major late tripartite leader
      containing pre-mRNAs. Interestingly, E4-ORF6 expression was also shown to
      stimulate i-leader exon skipping during a lytic virus infection.

PMID- 8264612
TI  - Specific repression of the yeast silent mating locus HMR by an adjacent telomere.
AB  - The yeast silent mating loci HML and HMR are located at opposite ends of
      chromosome III adjacent to the telomeres. Mutations in the N terminus of histone
      H4 have been previously found to derepress the yeast silent mating locus HML to a
      much greater extent than HMR. Although differences in the a and alpha mating-type
      regulatory genes and in the cis-acting silencer elements do not appear to
      strongly influence the level of derepression at HMR, we have found that the
      differential between the two silent cassettes is largely due to the position of
      the HMR cassette relative to the telomere on chromosome III. While HML is
      derepressed to roughly the same extent by mutations in histone H4 regardless of
      its chromosomal location, HMR is affected to different extends depending upon its
      chromosomal positioning. We have found that HMR is more severely derepressed by
      histone H4 mutations when positioned far from the telomere (cdc14 locus on
      chromosome VI) but is only minimally affected by the same mutations when
      integrated immediately adjacent to another telomere (ADH4 locus on chromosome
      VII). These data indicate that the degree of silencing at HMR is regulated in
      part by its neighboring telomere over a distance of at least 23 kb and that this
      form of regulation is unique for HMR and not present at HML. These data also
      indicate that histone H4 plays an important role in regulating the silenced state
      at both HML and HMR.

PMID- 8264613
TI  - In vitro selection of DNA elements highly responsive to the human T-cell
      lymphotropic virus type I transcriptional activator, Tax.
AB  - The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the
      ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding
      protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional
      enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc.
      Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the
      COOH-terminal region of Tax along with purified Tax and CREB proteins, we
      selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two
      distinct but related groups of sequences containing the cAMP response element
      (CRE) flanked by long runs of G and C residues in the 5' and 3' regions,
      respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone
      binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich
      sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5'
      or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel
      electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting
      analyses indicated that the G- and C-rich sequences flanking the CRE motif are
      crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are
      not in direct contact with the Tax-CREB complex. These data show that Tax
      recruits CREB to form a multiprotein complex that specifically recognizes the
      viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the
      obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal
      a novel mechanism for regulating the transcriptional activity of leucine zipper
      proteins like CREB.

PMID- 8264614
TI  - p42 mitogen-activated protein kinase and p90 ribosomal S6 kinase are selectively
      phosphorylated and activated during thrombin-induced platelet activation and
      aggregation.
AB  - Human platelets provide an excellent model system for the study of
      phosphorylation events during signal transduction and cell adhesion. Platelets
      are terminally differentiated cells that exhibit rapid phosphorylation of many
      proteins upon agonist-induced activation and aggregation. We have sought to
      identify the kinases as well as the phosphorylated substrates that participate in
      thrombin-induced signal transduction and platelet aggregation. In this study, we
      have identified two forms of mitogen-activated protein kinase (MAPK), p42mapk and
      p44mapk, in platelets. The data demonstrate that p42mapk but not p44mapk becomes
      phosphorylated on serine, threonine, and tyrosine during platelet activation.
      Immune complex kinase assays, gel renaturation assays, and a direct assay for
      MAPK activity in platelet extracts all support the conclusion that p42mapk but
      not p44mapk shows increased kinase activity during platelet activation. The
      activation of p42mapk, independently of p44mapk, in platelets is unique since in
      other systems, both kinases are coactivated by a variety of stimuli. We also show
      that platelets express p90rsk, a ribosomal S6 kinase that has previously been
      characterized as a substrate for MAPK. p90rsk is phosphorylated on serine in
      resting platelets, and this phosphorylation is enhanced upon thrombin-induced
      platelet activation. Immune complex kinase assays demonstrate that the activity
      of p90rsk is markedly increased during platelet activation. Another ribosomal S6
      protein kinase, p70S6K, is expressed by platelets but shows no change in kinase
      activity upon platelet activation with thrombin. Finally, we show that the
      increased phosphorylation and activity of both p42mapk and p90rsk does not
      require integrin-mediated platelet aggregation. Since platelets are
      nonproliferative cells, the signal transduction pathways that include p42mapk and
      p90rsk cannot lead to a mitogenic signal and instead may regulate cytoskeletal or
      secretory changes during platelet activation.

PMID- 8264615
TI  - Regulation of the T-cell receptor delta enhancer by functional cooperation
      between c-Myb and core-binding factors.
AB  - A T-cell-specific transcriptional enhancer lies within the J delta 3-C delta
      intron of the human T-cell receptor (TCR) delta gene. The 30-bp minimal enhancer
      element denoted delta E3 carries a core sequence (TGTGGTTT) that binds a T-cell
      specific factor, and that is necessary but not sufficient for transcriptional
      activation. Here we demonstrate that the transcription factor c-Myb regulates TCR
      delta enhancer activity through a binding site in delta E3 that is adjacent to
      the core site. Both v-Myb and c-Myb bind specifically to delta E3. The Myb site
      is necessary for enhancer activity, because a mutation that eliminates Myb
      binding abolishes transcriptional activation by the delta E3 element and by the
      370-bp TCR delta enhancer. Transfection of cells with a c-Myb expression
      construct upregulates delta E3 enhancer activity, whereas treatment of cells with
      an antisense c-myb oligonucleotide inhibits delta E3 enhancer activity. Since
      intact Myb and core sites are both required for delta E3 function, our data argue
      that c-Myb and core binding factors must cooperate to mediate transcriptional
      activation through delta E3. Efficient cooperation depends on the relative
      positioning of the Myb and core sites, since only one of two overlapping Myb
      sites within delta E3 is functional and alterations of the distance between this
      site and the core site disrupt enhancer activity. Cooperative regulation by c-Myb
      and core-binding factors is likely to play an important role in the control of
      gene expression during T-cell development.

PMID- 8264616
TI  - Analysis of the VPE sequences in the Caenorhabditis elegans vit-2 promoter with
      extrachromosomal tandem array-containing transgenic strains.
AB  - The Caenorhabditis elegans vit genes, encoding vitellogenins, are abundantly
      expressed in the adult hermaphrodite intestine. Two repeated elements, vit
      promoter element 1 (VPE1 [TGTCAAT]) and VPE2 (CTGATAA), have been identified in
      the 5' flanking DNA of each of the vit genes of C. elegans and Caenorhabditis
      briggsae. These elements have previously been shown to be needed for correctly
      regulated expression of a vit-2/vit-6 fusion gene in low-copy-number, integrated
      transgenes. Here we extend the analysis of the function of VPE1 and VPE2 by using
      transgenic lines carrying large, extrachromosomal arrays of the test genes. The
      results validate the use of such arrays for transgenic analysis of gene
      regulation in C. elegans, by confirming previous findings showing that the VPE1
      at -45 and both VPE2s are sites of activation. Additional experiments now
      indicate that when the -45 VPE1 is inverted or replaced by a VPE2, nearly total
      loss of promoter function results, suggesting that the highly conserved -45 VPE1
      plays a unique role in vit-2 promoter function. In contrast, single mutations
      eliminating the three upstream VPE1s are without effect. However, in combination
      in double and triple mutants, these upstream VPE1 mutations cause drastic
      reductions in expression levels. The -150 VPE2 can be replaced by a XhoI site
      (CTCGAG), and the -90 VPE2 can be eliminated, as long as the overlapping VPE1 is
      left intact, but when these two replacements are combined, activity is lost.
      Thus, the promoter must have at least one VPE2 and it must have at least two
      VPE1s, one at -45 and one additional upstream element.

PMID- 8264617
TI  - Efficient coupling with phosphatidylinositol 3-kinase, but not phospholipase C
      gamma or GTPase-activating protein, distinguishes ErbB-3 signaling from that of
      other ErbB/EGFR family members.
AB  - Recombinant expression of a chimeric EGFR/ErbB-3 receptor in NIH 3T3 fibroblasts
      allowed us to investigate cytoplasmic events associated with ErbB-3 signal
      transduction upon ligand activation. An EGFR/ErbB-3 chimera was expressed on the
      surface of NIH 3T3 transfectants as two classes of receptors possessing epidermal
      growth factor (EGF) binding affinities comparable to those of the wild-type EGF
      receptor (EGFR). EGF induced autophosphorylation in vivo of the chimeric receptor
      and DNA synthesis of EGFR/ErbB-3 transfectants with a dose response similar to
      that of EGFR transfectants. However, the ErbB-3 and EGFR cytoplasmic domains
      exhibited striking differences in their interactions with several known tyrosine
      kinase substrates. We demonstrated strong association of phosphatidylinositol 3
      kinase activity with the chimeric receptor upon ligand activation comparable in
      efficiency with that of the platelet-derived growth factor receptor, while the
      EGFR exhibited a 10- to 20-fold-lower efficiency in phosphatidylinositol 3-kinase
      recruitment. By contrast, both phospholipase C gamma and GTPase-activating
      protein failed to associate with or be phosphorylated by the ErbB-3 cytoplasmic
      domain under conditions in which they coupled with the EGFR. In addition, though
      certain signal transmitters, including Shc and GRB2, were recruited by both
      kinases, EGFR and ErbB-3 elicited tyrosine phosphorylation of distinct sets of
      intracellular substrates. Thus, our findings show that ligand activation of the
      ErbB-3 kinase triggers a cytoplasmic signaling pathway that hitherto is unique
      within this receptor subfamily.

PMID- 8264618
TI  - Concerted action of RAS and G proteins in the sexual response pathways of
      Schizosaccharomyces pombe.
AB  - We have shown that the expression of mam2, the gene encoding the
      Schizosaccharomyces pombe P-factor pheromone receptor, is dependent upon
      components of the pheromone signal transduction pathway, including Ras1, Gpa1,
      Byr1 and Byr2, each of which is required for both conjugation and sporulation.
      Studies of the expression of mam2 in mutant S. pombe cells confirm previous
      conclusions, based on the ability of cells to sporulate, that the Byr1 protein
      kinase acts downstream of the Byr2 protein kinase and that both act downstream of
      Ras1, the S. pombe RAS homolog, and Gpa1, the G alpha component that mediates the
      occupancy of the mam2 receptor. In addition, our present studies show that Ras1
      and Gpa1 each act downstream from the other and hence act in concert. The Spk1
      kinase, which is required for conjugation and sporulation and which is a
      structural and functional homolog of the vertebrate MAP kinases, is not required
      for mam2 expression.

PMID- 8264619
TI  - Interactions between DNA-bound trimers of the yeast heat shock factor.
AB  - The heat shock transcription factor (HSF) is a trimer that binds to DNA
      containing inverted repeats of the sequence nGAAn. HSF can bind DNA with the
      sequence nGAAnnTTCn or with the sequence nTTCnnGAAn, with little preference for
      either sequence over the other. However, (nGAAnnTTCn)2 is considerably less
      active as a heat shock response element (HSE) than is (nTTCnnGAAn)2. The
      electrophoretic mobilities of DNA-protein complexes and chemical cross-linking
      between protein monomers indicate that the sequence (nGAAnnTTCn)2 is capable of
      binding a single HSF trimer. In contrast, the sequence with higher biological
      activity, (nTTCnnGAAn)2, is capable of binding two trimers. Thus, the ability of
      four-nGAAn-element HSEs to bind one or two trimers depends on the permutation
      with which the elements are presented. A survey of naturally occurring HSEs shows
      the sequence (nTTCnnGAAn)2 to be the more prevalent. We suggest that the greater
      ability of one permutation over the other to bind two HSF trimers accounts for
      the initial identification of the naturally occurring heat shock consensus
      sequence as a region of dyad symmetry.

PMID- 8264620
TI  - A new function for a phosphotyrosine phosphatase: linking GRB2-Sos to a receptor
      tyrosine kinase.
AB  - Autophosphorylated growth factor receptors provide binding sites for the src
      homology 2 domains of intracellular signaling molecules. In response to epidermal
      growth factor (EGF), the activated EGF receptor binds to a complex containing the
      signaling protein GRB2 and the Ras guanine nucleotide-releasing factor Sos,
      leading to activation of the Ras signaling pathway. We have investigated whether
      the platelet-derived growth factor (PDGF) receptor binds GRB2-Sos. In contrast
      with the EGF receptor, the GRB2 does not bind to the PDGF receptor directly.
      Instead, PDGF stimulation induces the formation of a complex containing GRB2; 70
      , 80-, and 110-kDa tyrosine-phosphorylated proteins; and the PDGF receptor.
      Moreover, GRB2 binds directly to the 70-kDa protein but not to the PDGF receptor.
      Using a panel of PDGF beta-receptor mutants with altered tyrosine phosphorylation
      sites, we identified Tyr-1009 in the PDGF receptor as required for GRB2 binding.
      Binding is inhibited by a phosphopeptide containing a YXNX motif. The protein
      tyrosine phosphatase Syp/PTP1D/SHPTP2/PTP2C is approximately 70 kDa, binds to the
      PDGF receptor via Tyr-1009, and contains several YXNX sequences. We found that
      the 70-kDa protein that binds to the PDGF receptor and to GRB2 comigrates with
      Syp and is recognized by anti-Syp antibodies. Furthermore, both GRB2 and Sos
      coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2
      binds directly to tyrosine-phosphorylated Syp in vitro. These results indicate
      that GRB2 interacts with different growth factor receptors by different
      mechanisms and the cytoplasmic phosphotyrosine phosphatase Syp acts as an adapter
      between the PDGF receptor and the GRB2-Sos complex.

PMID- 8264621
TI  - The C-protein tetramer binds 230 to 240 nucleotides of pre-mRNA and nucleates the
      assembly of 40S heterogeneous nuclear ribonucleoprotein particles.
AB  - A series of in vitro protein-RNA binding studies using purified native (C1)3C2
      and (A2)3B1 tetramers, total soluble heterogeneous nuclear ribonucleoprotein
      (hnRNP), and pre-mRNA molecules differing in length and sequence have revealed
      that a single C-protein tetramer has an RNA site size of 230 to 240 nucleotides
      (nt). Two tetramers bind twice this RNA length, and three tetramers fold
      monoparticle lengths of RNA (700 nt) into a unique 19S triangular complex. In the
      absence of this unique structure, the basic A- and B-group proteins bind RNA to
      form several different artifactual structures which are not present in
      preparations of native hnRNP and which do not function in hnRNP assembly. Three
      (A2)3B1 tetramers bind the 19S complex to form a 35S assembly intermediate.
      Following UV irradiation to immobilize the C proteins on the packaged RNA, the
      19S triangular complex is recovered as a remnant structure from both native and
      reconstituted hnRNP particles. C protein-RNA complexes composed of three, six, or
      nine tetramers (one, two, or three triangular complexes) nucleate the
      stoichiometric assembly of monomer, dimer, and trimer hnRNP particles. The
      binding of C-protein tetramers to RNAs longer than 230 nt is through a self
      cooperative combinatorial mode. RNA packaged in the 19S complex and in 40S hnRNP
      particles is efficiently spliced in vitro. These findings demonstrate that
      formation of the triangular C protein-RNA complex is an obligate first event in
      the in vitro and probably the in vivo assembly the 40S hnRNP core particle, and
      they provide insight into the mechanism through which the core proteins package
      700-nt increments of RNA. These findings also demonstrate that unless excluded by
      other factors, the C proteins are likely to be located along the length of
      nascent transcripts.

PMID- 8264622
TI  - Functional evidence for a second tumor suppressor gene on human chromosome 17.
AB  - The development and progression of human tumors often involves inactivation of
      tumor suppressor gene function. Observations that specific chromosome deletions
      correlate with distinct groups of cancer suggest that some types of tumors may
      share common defective tumor suppressor genes. In support of this notion, our
      initial studies showed that four human carcinoma cell lines belong to the same
      complementation group for tumorigenic potential. In this investigation, we have
      extended these studies to six human soft tissue sarcoma cell lines. Our data
      showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line
      and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid
      cells between the PNET cell line and five other soft tissue sarcoma cell lines
      remained highly tumorigenic, suggesting at least one common genetic defect in the
      control of tumorigenic potential in these cells. To determine the location of
      this common tumor suppressor gene, we examined biochemical and molecular
      polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid
      cells between the PNET cell line and a normal human fibroblast. The data showed
      that loss of the fibroblast-derived chromosome 17 correlated with the conversion
      from nontumorigenic to tumorigenic cells. Transfer of two different chromosome
      17s containing a mutant form of the p53 gene into the PNET cell line caused
      suppression of tumorigenic potential, implying the presence of a second tumor
      suppressor gene on chromosome 17.

PMID- 8264623
TI  - Telomeric DNA sequence and structure following de novo telomere synthesis in
      Euplotes crassus.
AB  - To learn more about the mechanism of de novo telomere synthesis, we have
      characterized the sequence and structure of newly synthesized telomeres from
      Euplotes crassus. E. crassus is a particularly useful organism for studying
      telomere synthesis because millions of telomeres are made in each cell at a well
      defined time during the sexual stage of the life cycle. These newly synthesized
      telomeres are approximately 50 bp longer than mature macronuclear telomeres. We
      have investigated the structure of the newly synthesized telomeres and have found
      that they are much more heterogeneous in length than mature telomeres. Most of
      the heterogeneity is present on the G-rich strand, indicating that the length of
      this strand is rather loosely controlled. In contrast, the length of the C-rich
      strand is much less variable, suggesting that synthesis of this strand is the
      more precisely regulated step in telomere addition. The G-rich strand exhibits
      variability both in the total number of G4T4 repeats and in the identity of the
      terminal nucleotide. In most cases, the G-rich strnd extends beyond the C-rich
      strand to leave a 3' overhang. While the size of this overhang is variable, the
      median length is 10 nucleotides. This research provides the first detailed
      picture of a newly synthesized telomere and has allowed us to formulate a model
      to describe the various steps involved in de novo telomere synthesis.

PMID- 8264624
TI  - Alternative 5' splice site selection induced by heat shock.
AB  - The mouse HSP47 gene consists of six exons separated by five introns. Three HSP47
      cDNAs differing only in their 5' noncoding regions have been reported. One of
      these alternatively spliced mRNAs was detected only after heat shock, which
      caused an alternative 5' splice donor site selection. Other stress inducers,
      including an amino acid analog and sodium arsenite, had no effect on the
      alternative splicing. The alternatively spliced mRNA, which was 169 nucleotides
      longer in the 5' noncoding region compared to mRNA transcribed in non-heat shock
      conditions, was efficiently translated under heat shock conditions. This novel
      finding that alternative splicing is caused by artificial treatment like heat
      shock will provide a useful in vivo model for understanding the exon-intron
      recognition mechanism as well as heat shock-induced alterations in gene
      expression.

PMID- 8264626
TI  - Selection for arsenite resistance causes reversible changes in minicircle
      composition and kinetoplast organization in Leishmania mexicana.
AB  - Certain minor minicircle sequence classes in the kinetoplast DNA (kDNA) networks
      of arsenite- or tunicamycin-resistant Leishmania mexicana amazonensis variants
      whose nuclear DNA is amplified appear to be preferentially selected to replicate
      (S. T. Lee, C. Tarn, and K. P. Chang, Mol. Biochem. Parasitol. 58:187-204, 1993).
      These sequences replace the predominant wild-type minicircle sequences to become
      dominant species in the kDNA network. The switch from wild-type-specific to
      variant-specific minicircles takes place rapidly within the same network, the
      period of minicircle dominance changes being defined as the transition period. To
      investigate the structural organization of the kDNA networks during this
      transition period, we analyzed kDNA from whole arsenite-resistant Leishmania
      parasites by dot hybridization with sequence-specific DNA probes and by electron
      microscopic examination of isolated kDNA networks in vitro. Both analyses
      concluded that during the switch of dominance the predominant wild-type
      minicircle class was rapidly lost and that selective replication of variant
      specific minicircles subsequently filled the network step by step. There was a
      time during the transition when few wild-type- or variant-specific minicircles
      were present, leaving the network almost empty and exposing a species of thick,
      long, fibrous DNA which seemed to form a skeleton for the network. Both
      minicircles and maxicircles were found to attach to these long DNA fibrils. The
      nature of the long DNA fibrils is not clear, but they may be important in
      providing a framework for the network structure and a support for the replication
      of minicircles and maxicircles.

PMID- 8264625
TI  - The Schizosaccharomyces pombe casein kinase II alpha and beta subunits:
      evolutionary conservation and positive role of the beta subunit.
AB  - Casein kinase II is a key regulatory enzyme involved in many cellular processes,
      including the control of growth and cell division. We report the molecular
      cloning and sequencing of cDNAs encoding the alpha and the beta subunits of
      casein kinase II of Schizosaccharomyces pombe. The deduced amino acid sequence of
      Cka1, the alpha catalytic subunit, shows high sequence similarity to alpha
      subunits identified in other species. The amino acid sequence of Ckb1, the S.
      pombe beta subunit, is 57% identical to that of the human beta subunit. Cka1
      overexpression results in no detectable phenotype. In contrast, Ckb1
      overexpression inhibits cell growth and cytokinesis, with formation of
      multiseptated cells. Disruption of the ckb1+ gene causes a cold-sensitive
      phenotype and abnormalities in cell shape. In these cells, the casein kinase II
      activity is reduced to undetectable levels, demonstrating that Ckb1 is required
      for enzyme activity in vivo. In agreement with this, the activity measured in a
      strain expressing high levels of Cka1 is enhanced only when the Ckb1 protein is
      coexpressed. Altogether, our data suggest that Ckb1 is a positive regulator of
      the enzyme activity, and that it plays a role in mediating the interaction of
      casein kinase II with downstream targets and/or with additional regulators.

PMID- 8264627
TI  - An upstream enhancer regulating brown-fat-specific expression of the
      mitochondrial uncoupling protein gene.
AB  - Previous studies on the regulation of a Ucp minigene in transgenic mice
      demonstrated that the sequences necessary for brown-fat-specific expression and
      inducibility by norepinephrine were located in the 5' flanking region between 1
      and 2.8 kb from the transcriptional start site. We have investigated this region
      in more detail in cultured mouse brown adipocyte tumor cells. Deletion analysis
      of two types of chloramphenicol acetyltransferase reporter gene constructs under
      control of either the Ucp promoter or a heterologous herpes simplex virus-tk
      promoter defined an enhancer in a 220-bp HindIII-XbaI fragment which was
      essential for both brown fat specificity and norepinephrine inducibility. Site
      directed mutagenesis of the reporter gene constructs established that independent
      mutations to a cyclic AMP-responsive element (CRE-2) or one of two TTCC motifs
      (BRE [brown fat regulatory element]), all within 17 bp, eliminated transient
      expression. Competitive DNA mobility shift assays with probes of the CRE and BRE
      motifs indicate that nuclear proteins interact with these motifs in a
      cooperative, synergistic manner. While these CRE-BRE probes do not show changes
      in binding which is dependent on norepinephrine treatment, a probe containing a
      third TTCC motif located 130 bp downstream of BRE-1 does show this dependency.
      The results indicate that a complex interaction of the CRE and BRE motifs, which
      cannot be functionally separated, control Ucp expression.

PMID- 8264628
TI  - TATA box-binding protein (TBP) is a constituent of the polymerase I-specific
      transcription initiation factor TIF-IB (SL1) bound to the rRNA promoter and shows
      differential sensitivity to TBP-directed reagents in polymerase I, II, and III
      transcription factors.
AB  - The role of the Acanthamoeba castellanii TATA-binding protein (TBP) in
      transcription was examined. Specific antibodies against the nonconserved N
      terminal domain of TBP were used to verify the presence of TBP in the fundamental
      transcription initiation factor for RNA polymerase I, TIF-IB, and to demonstrate
      that TBP is part of the committed initiation complex on the rRNA promoter. The
      same antibodies inhibit transcription in all three polymerase systems, but they
      do so differentially. Oligonucleotide competitors were used to evaluate the
      accessibility of the TATA-binding site in TIF-IB, TFIID, and TFIIIB. The results
      suggest that insertion of TBP into the polymerase II and III factors is more
      similar than insertion into the polymerase I factor.

PMID- 8264629
TI  - Effect of sequence context at stop codons on efficiency of reinitiation in GCN4
      translational control.
AB  - Translational control of the GCN4 gene involves two short open reading frames in
      the mRNA leader (uORF1 and uORF4) that differ greatly in the ability to allow
      reinitiation at GCN4 following their own translation. The low efficiency of
      reinitiation characteristic of uORF4 can be reconstituted in a hybrid element in
      which the last codon of uORF1 and 10 nucleotides 3' to its stop codon (the
      termination region) are substituted with the corresponding nucleotides from
      uORF4. To define the features of these 13 nucleotides that determine their
      effects on reinitiation, we separately randomized the sequence of the third codon
      and termination region of the uORF1-uORF4 hybrid and selected mutant alleles with
      the high-level reinitiation that is characteristic of uORF1. The results indicate
      that many different A+U-rich triplets present at the third codon of uORF1 can
      overcome the inhibitory effect of the termination region derived from uORF4 on
      the efficiency of reinitiation at GCN4. Efficient reinitiation is not associated
      with codons specifying a particular amino acid or isoacceptor tRNA. Similarly, we
      found that a diverse collection of A+U-rich sequences present in the termination
      region of uORF1 could restore efficient reinitiation at GCN4 in the presence of
      the third codon derived from uORF4. To explain these results, we propose that
      reinitiation can be impaired by stable base pairing between nucleotides flanking
      the uORF1 stop codon and either the tRNA which pairs with the third codon, the
      rRNA, or sequences located elsewhere in GCN4 mRNA. We suggest that these
      interactions delay the resumption of scanning following peptide chain termination
      at the uORF and thereby lead to ribosome dissociation from the mRNA.

PMID- 8264630
TI  - Enhanced translational efficiency of a novel transforming growth factor beta 3
      mRNA in human breast cancer cells.
AB  - The mRNA for transforming growth factor beta 3 (TGF-beta 3) includes a long (1.1
      kb) 5' noncoding region which exerts a potent inhibitory effect on translational
      efficiency. We now report that many human breast cancer cell lines (T47-D, SK-BR
      3, ZR-75-1, and BT-474) express two mRNA species for TGF-beta 3: the 3.5-kb
      transcript previously described as the only TGF-beta 3 mRNA species in cells and
      a novel 2.6-kb transcript which lacks approximately 870 nucleotides from the 5'
      noncoding region. The 5' end of the shorter transcript was sequenced,
      establishing it to be a 5' truncation of the full-length TGF-beta 3 transcript.
      Estradiol decreased mRNA levels of both TGF-beta 3 mRNA transcripts to an
      equivalent degree in estrogen receptor-positive cells. In contrast, the synthetic
      progestin gestodene altered the relative abundance of the two transcripts,
      preferentially diminishing the expression of the 2.6-kb transcript. The potential
      for enhanced mRNA translation attributable to the shorter 5' noncoding region was
      evaluated by transfection of cells with chimeric plasmid constructs in which the
      transcription unit consisted of coding sequence for chloramphenicol
      acetyltransferase downstream of the 5' noncoding sequence from TGF-beta 3. The
      translational efficiency of chloramphenicol acetyltransferase-encoding mRNA
      containing the shorter 5' noncoding region of the 2.6-kb TGF-beta 3 transcript
      was approximately seven times greater than with the full-length 5' noncoding
      region of TGF-beta 3. Polysome analysis of TGF-beta 3 mRNA in SK-BR-3 cells
      supported the hypothesis that the 2.6-kb transcript was more actively engaged in
      translation.

PMID- 8264631
TI  - Dissection of the ADR1 protein reveals multiple, functionally redundant
      activation domains interspersed with inhibitory regions: evidence for a repressor
      binding to the ADR1c region.
AB  - The yeast transcriptional activator ADR1 is required for expression of the
      glucose-repressible alcohol dehydrogenase gene (ADH2), as well as genes involved
      in glycerol metabolism. The N-terminal half of the ADR1 protein was shown to
      contain three separate transactivation domains, including one (TADI) that
      encompasses the zinc finger DNA-binding domain. While TADII and TADIII were shown
      to be functionally redundant in activating ADH2 expression, deletion of only
      TADIII impaired ADR1 control of glycerol metabolism genes. None of these
      activation domains appeared to be carbon source regulated when separated from the
      ADH2 promoter context. Interspersed among these activation domains were two
      regions which, when removed, increased ADR1 activity; one was localized to the
      site of ADR1c mutations (residues 227 to 239) that allow glucose-insensitive ADH2
      expression. The 227-to-239 region blocked ADR1 activity independently of the TAD
      present on ADR1, ADR1 DNA binding, and specific ADH2 promoter sequences. In
      addition, this region inhibited the function of a heterologous transcriptional
      activator. These results are consistent with the existence of an extragenic
      factor that binds the ADR1c region and represses ADR1 activity and suggest that
      other factors are responsible for aiding ADR1 in the carbon source regulation of
      ADH2.

PMID- 8264632
TI  - Neurofibromin can inhibit Ras-dependent growth by a mechanism independent of its
      GTPase-accelerating function.
AB  - The NF1 gene, which is altered in patients with type 1 neurofibromatosis, has
      been postulated to function as a tumor suppressor gene. The NF1 protein product
      neurofibromin stimulates the intrinsic GTPase activity of active GTP-bound Ras,
      thereby inactivating it. Consistent with a tumor suppressor function, we have
      found that the introduction of NF1 in melanoma cell lines that are deficient in
      neurofibromin inhibited their growth and induced their differentiation. In
      addition, overexpression of neurofibromin in NIH 3T3 cells was growth inhibitory
      but did not alter the level of GTP.Ras in the cells. Transformation by v-ras,
      whose protein product is resistant to GTPase stimulation by neurofibromin, was
      inhibited in a cell line overexpressing neurofibromin, while transformation by v
      raf was not altered. The results demonstrate that NF1 is a tumor suppressor gene
      that can inhibit Ras-dependent growth by a regulatory mechanism that is
      independent of neurofibromin's ability to stimulate Ras GTPase.

PMID- 8264633
TI  - NIH 3T3 cells stably transfected with the gene encoding phosphatidylcholine
      hydrolyzing phospholipase C from Bacillus cereus acquire a transformed phenotype.
AB  - In order to determine whether chronic elevation of intracellular diacylglycerol
      levels generated by hydrolysis of phosphatidylcholine (PC) by PC-hydrolyzing
      phospholipase C (PC-PLC) is oncogenic, we generated stable transfectants of NIH
      3T3 cells expressing the gene encoding PC-PLC from Bacillus cereus. We found that
      constitutive expression of this gene (plc) led to transformation of NIH 3T3 cells
      as evidenced by anchorage-independent growth in soft agar, formation of
      transformed foci in tissue culture, and loss of contact inhibition. The plc
      transfectants displayed increased intracellular levels of diacylglycerol and
      phosphocholine. Expression of B. cereus PC-PLC was confirmed by immunoperoxidase
      and immunofluorescence staining with an affinity-purified anti-PC-PLC antibody.
      The NIH 3T3 clones expressing plc induced DNA synthesis, progressed through the
      cell cycle in the absence of added mitogens, and showed significant growth in low
      concentration serum. Transfection with an antisense plc expression vector led to
      a loss of PC-PLC expression accompanied by a complete reversion of the
      transformed phenotype, suggesting that plc expression was required for
      maintenance of the transformed state. Taken together, our results show that
      chronic stimulation of PC hydrolysis by an unregulated PC-PLC enzyme is oncogenic
      to NIH 3T3 cells.

PMID- 8264634
TI  - c-jun inhibits transcriptional activation by the insulin enhancer, and the
      insulin control element is the target of control.
AB  - Selective transcription of the insulin gene in pancreatic beta cells is regulated
      by its enhancer, located between nucleotides -340 and -91 relative to the
      transcription start site. One of the principal control elements within the
      enhancer is found between nucleotides -100 and -91 (GCCATCTGCT, referred to as
      the insulin control element [ICE]) and is regulated by both positive- and
      negative-acting transcription factors in the helix-loop-helix (HLH) family. It
      was previously shown that the c-jun proto-oncogene can repress insulin gene
      transcription. We have found that c-jun inhibits ICE-stimulated transcription.
      Inhibition of ICE-directed transcription is mediated by sequences within the
      carboxy-terminal region of the protein. These c-jun sequences span an activation
      domain and the basic leucine zipper DNA binding-dimerization region of the
      protein. Both regions of c-jun are conserved within the other members of the jun
      family: junB and junD. These proteins also suppress ICE-mediated transcription.
      The jun proteins do not appear to inhibit insulin gene transcription by binding
      directly to the ICE. c-jun and junB also block the trans-activation potential of
      two skeletal muscle-specific HLH proteins, MyoD and myogenin. These results
      suggests that the jun proteins may be common transcription control factors used
      in skeletal muscle and pancreatic beta cells to regulate HLH-mediated activity.
      We discuss the possible significance of these observations to insulin gene
      transcription in pancreatic beta cells.

PMID- 8264636
TI  - Intragenic activating and repressing elements control transcription from the
      adenovirus IVa2 initiator.
AB  - The downstream stimulatory segment of the adenovirus type 2 IVa promoter includes
      a TA-rich sequence that binds recombinant TATA-binding proteins (TBP) in vitro.
      We now demonstrate that when placed upstream of the IVa2, initiator, this TA-rich
      sequence operated as a TATA element but exhibited significantly lower
      transcriptional and TBP-binding activities than did the TATA box of the
      adenovirus major late (ML) promoter. In sharp contrast, changing the IVa2 TA-rich
      sequence in its natural, intragenic context to the ML TATA sequence increased the
      activity of the IVa2 promoter only slightly. In view of this discrepancy, we
      examined the effects of single, double, and clustered point mutations in the
      downstream sequence on the activity of a minimal IVa2 promoter. Mutations between
      positions +21 and +29 inhibited IVa2 transcription, in some cases to the very low
      level directed by the IVa2 initiator alone. By contrast, substitutions within the
      TA-rich sequence increased the efficiency of IVa2 transcription. These results
      indicated that the downstream, TA-rich sequence does not function as an
      intragenic TFIID-binding site but rather is included within a negative regulatory
      element. Electrophoretic mobility shift and methylation interference assays using
      wild-type and mutated, intragenic promoter sequences identified a HeLa cell
      component whose binding to the sequence +11 to +27 correlated with repression of
      IVa2 transcription, suggesting that a negative regulatory element is superimposed
      upon the intragenic sequence required for efficient transcription from the IVa2
      initiator.

PMID- 8264635
TI  - An epidermal growth factor receptor/ret chimera generates mitogenic and
      transforming signals: evidence for a ret-specific signaling pathway.
AB  - A chimeric expression vector which encoded for a molecule encompassing the
      extracellular domain of the epidermal growth factor (EGF) receptor (EGFR) and the
      intracellular domain of the ret kinase (EGFR/ret chimera) was generated. Upon
      ectopic expression in mammalian cells, the EGFR/ret chimera was correctly
      synthesized and transported to the cell surface, where it was shown capable of
      binding EGF and transducing an EGF-dependent signal intracellularly. Thus, the
      EGFR/ret chimera allows us to study the biological effects and biochemical
      activities of the ret kinase under controlled conditions of activation.
      Comparative analysis of the growth-promoting activity of the EGFR/ret chimera
      expressed in fibroblastic or hematopoietic cells revealed a biological phenotype
      clearly distinguishable from that of the EGFR, indicating that the two kinases
      couple with mitogenic pathways which are different to some extent. Analysis of
      biochemical pathways implicated in the transduction of mitogenic signals also
      evidenced significant differences between the ret kinase and other receptor
      tyrosine kinases. Thus, the sum of our results indicates the existence of a ret
      specific pathway of mitogenic signaling.

PMID- 8264637
TI  - An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III.
AB  - XRCC1, the human gene that fully corrects the Chinese hamster ovary DNA repair
      mutant EM9, encodes a protein involved in the rejoining of DNA single-strand
      breaks that arise following treatment with alkylating agents or ionizing
      radiation. In this study, a cDNA minigene encoding oligohistidine-tagged XRCC1
      was constructed to facilitate affinity purification of the recombinant protein.
      This construct, designated pcD2EHX, fully corrected the EM9 phenotype of high
      sister chromatid exchange, indicating that the histidine tag was not detrimental
      to XRCC1 activity. Affinity chromatography of extract from EM9 cells transfected
      with pcD2EHX resulted in the copurification of histidine-tagged XRCC1 and DNA
      ligase III activity. Neither XRCC1 or DNA ligase III activity was purified during
      affinity chromatography of extract from EM9 cells transfected with pcD2EX, a cDNA
      minigene that encodes untagged XRCC1, or extract from wild-type AA8 or
      untransfected EM9 cells. The copurification of DNA ligase III activity with
      histidine-tagged XRCC1 suggests that the two proteins are present in the cell as
      a complex. Furthermore, DNA ligase III activity was present at lower levels in
      EM9 cells than in AA8 cells and was returned to normal levels in EM9 cells
      transfected with pcD2EHX or pcD2EX. These findings indicate that XRCC1 is
      required for normal levels of DNA ligase III activity, and they implicate a major
      role for this DNA ligase in DNA base excision repair in mammalian cells.

PMID- 8264638
TI  - Binding of TFIID and MEF2 to the TATA element activates transcription of the
      Xenopus MyoDa promoter.
AB  - Members of the MyoD family of helix-loop-helix proteins control expression of the
      muscle phenotype by regulating the activity of subordinate genes. To investigate
      processes that control the expression of myogenic factors and regulate the
      establishment and maintenance of the skeletal muscle phenotype, we have analyzed
      sequences necessary for transcription of the maternally expressed Xenopus MyoD
      (XMyoD) gene. A 3.5-kb DNA fragment containing the XMyoDa promoter was expressed
      in a somite-specific manner in injected frog embryos. The XMyoDa promoter was
      active in oocytes and cultured muscle cells but not in fibroblasts or nonmuscle
      cell lines. A 58-bp fragment containing the transcription initiation site, a GC
      rich region, and overlapping binding sites for the general transcription factor
      TFIID and the muscle-specific factor MEF2 was sufficient for muscle-specific
      transcription. Transcription of the minimal XMyoDa promoter in nonmuscle cells
      was activated by expression of Xenopus MEF2 (XMEF2) and required binding of both
      MEF2 and TFIID to the TATA motif. These results demonstrate that the XMyoDa TATA
      motif is a target for a cell-type-specific regulatory factor and suggests that
      MEF2 stabilizes and amplifies XMyoDa transcription in mesodermal cells committed
      to the muscle phenotype.

PMID- 8264639
TI  - Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms
      heterodimers with both Fos and Jun.
AB  - The v-maf oncogene, identified from AS42 avian retrovirus, encodes a nuclear bZip
      protein. To elucidate the molecular mechanism of cell transformation induced by
      this oncogene, we determined the specific binding sequences of its product. Maf
      protein recognized two types of relatively long palindromic consensus sequences,
      TGCTGACTCAGCA and TGCTGACGTCAGCA, at roughly equal efficiency. The middle parts
      of these Maf-binding sequences completely match with two binding sequences for AP
      1 transcription factor, i.e., phorbol 12-O-tetradecanoate-13-acetate (TPA)
      responsive element (TRE) and cyclic AMP responsive element, suggesting partial
      overlapping of the target genes for Maf and AP-1. Furthermore, Maf efficiently
      formed heterodimers with the components of AP-1, Fos and Jun, through their
      leucine zipper structures, and these heterodimers show binding specificities
      distinct from those for Maf-Maf and Jun-Jun homodimers. Thus, a multiple
      combination of the dimers should generate a greatly expanded repertoire of
      transcriptional regulatory potential. DNA data base search for the Maf-binding
      consensus sequences suggested that some of the TRE-like cis elements reported
      previously may actually be the targets for Maf family proteins or their
      heterodimers with other bZip proteins.

PMID- 8264640
TI  - The Drosophila dorsal morphogen represses the tolloid gene by interacting with a
      silencer element.
AB  - The dorsal protein (DL) regulates the transcriptional activity of several genes
      that determine cell fate along the dorsoventral axis of the Drosophila
      melanogaster embryo. DL is present at high levels in ventral nuclei, where it
      activates some genes (twi and sna) and represses others (zen, dpp, and tld). DL
      shows homology to the Rel family of proteins and interacts with specific DNA
      sequences in the regulatory regions of its target genes. The distal portion of
      the zen gene acts as a silencer that can mediate the repression of a heterologous
      promoter in ventral regions of the embryo. It contains four DL binding sites
      which alone are sufficient for activation but not repression. Here we analyze the
      interaction of DL with another one of its repressed targets, the tolloid (tld)
      gene. Approximately 800 bp of 5'-flanking sequences upstream of the tld coding
      region were shown to drive an expression pattern indistinguishable from the wild
      type pattern. A 423-bp fragment located within these sequences contains two DL
      binding sites and was shown to act as a silencer to mediate ventral repression.
      Point mutations in the sites abolish not only DNA binding but also ventral
      repression. We discuss a comparison of the DNA sequences from the zen and tld
      promoters and the possible mechanisms of transcriptional silencing.

PMID- 8264641
TI  - TATA-binding protein and nuclear differentiation in Tetrahymena thermophila.
AB  - Unambiguous TATA boxes have not been identified in upstream sequences of
      Tetrahymena thermophila genes analyzed to date. To begin a characterization of
      the promoter requirements for RNA polymerase II, the gene encoding TATA-binding
      protein (TBP) was cloned from this species. The derived amino acid sequence for
      the conserved C-terminal domain of Tetrahymena TBP is one of the most divergent
      described and includes a unique 20-amino-acid C-terminal extension. Polyclonal
      antibodies generated against a fragment of Tetrahymena TBP recognize a 36-kDa
      protein in macronuclear preparations and also cross-react with yeast and human
      TBPs. Immunocytochemistry was used to examine the nuclear localization of TBP
      during growth, starvation, and conjugation (the sexual phase of the life cycle).
      The transcriptionally active macronuclei stained at all stages of the life cycle.
      The transcriptionally inert micronuclei did not stain during growth or starvation
      but surprisingly stained with anti-TBP throughout early stages of conjugation.
      Anti-TBP staining disappeared from developing micronuclei late in conjugation,
      corresponding to the onset of transcription in developing macronuclei. Since
      micronuclei do not enlarge or divide at this time, loss of TBP appears to be an
      active process. Thus, the transcriptional differences between macro- and
      micronuclei that arise during conjugation are associated with the loss of a major
      component of the basal transcription apparatus from developing micronuclei rather
      than its appearance in developing macronuclei.

PMID- 8264642
TI  - The effector domain of Rab6, plus a highly hydrophobic C terminus, is required
      for Golgi apparatus localization.
AB  - C-terminal lipid modifications are essential for the interaction of Ras-related
      proteins with membranes. While all Ras proteins are farnesylated and some
      palmitoylated, the majority of other Ras-related proteins are geranylgeranylated.
      One such protein, Rab6, is associated with the Golgi apparatus and has a C
      terminal CXC motif that is geranylgeranylated on both cysteines. We show here
      that farnesylation alone cannot substitute for geranylgeranylation in targeting
      Rab6 to the Golgi apparatus and that whereas Ras proteins that are farnesylated
      and palmitoylated are targeted to the plasma membrane, mutant Rab proteins that
      are both farnesylated and palmitoylated associate with the Golgi apparatus. Using
      chimeric Ras-Rab proteins, we find that there are sequences in the N-terminal 71
      amino acids of Rab6 which are required for Golgi complex localization and show
      that these sequences comprise or include the effector domain. The C-terminal
      hypervariable domain is not essential for the Golgi complex targeting of Rab6 but
      is required to prevent prenylated and palmitoylated Rab6 from localizing to the
      plasma membrane. Functional analysis of these mutant Rab6 proteins in
      Saccharomyces cerevisiae shows that wild-type Rab6 and C-terminal mutant Rab6
      proteins which localize to the Golgi apparatus in mammalian cells can complement
      the temperature-sensitive phenotype of ypt6 null mutants. Interestingly,
      therefore, the C-terminal hypervariable domain of Rab6 is not required for this
      protein to function in S. cerevisiae.

PMID- 8264643
TI  - Expression and function of TRK-B and BDNF in human neuroblastomas.
AB  - There is considerable interest in the role of the TRK family of neuotrophin
      receptors in regulating growth and differentiation in normal and neoplastic nerve
      cells. A neuroblastoma is a common pediatric tumor derived from the neural crest,
      and the majority of favorable neuroblastomas express a high level of TRK-A mRNA.
      However, little is known about the expression or function of TRK-B in these
      tumors. TRK-B encodes a tyrosine kinase that binds to brain-derived neuotrophic
      factor (BDNF), as well as neurotrophin-3 (NT-3) and NT-4/5. We have studied the N
      myc-amplified human neuroblastoma cell line, SMS-KCN, which expresses both TRK-B
      and BDNF. Exogenous BDNF induces tyrosine phosphorylation of TRK-B as well as
      phosphorylation of phospholipase C-gamma 1, the extracellular signal-regulated
      kinases 1 and 2, and phosphatidylinositol-3 kinase. BDNF also induces expression
      of the immediate-early genes c-FOS and NGFI-A but not NGFI-B or NGFI-C. In
      addition, BDNF appears to promote cell survival and neurite outgrowth. SMS-KCN
      cells also express TRK-A, which is phosphorylated in response to nerve growth
      factor. However, the downstream TRK-A signaling is apparently defective. Finally,
      we determined that in a series of 74 primary neuroblastomas, 36% express TRK-B
      mRNA, 68% express BDNF mRNA, and 31% express both. Truncated TRK-B appears to be
      preferentially expressed in more-differentiated tumors (ganglioneuromas and
      ganglioneuroblastomas), whereas full-length TRK-B is expressed almost exclusively
      in immature neuroblastomas with N-myc amplification. Our findings suggest that in
      TRK-B-expressing human neuroblastomas, BDNF promotes survival and induces neurite
      outgrowth in an autocrine or paracrine manner. The BDNF/TRK-B pathway may be
      particularly important for growth and differentiation of neuroblastomas with N
      myc amplification.

PMID- 8264644
TI  - Interaction between the Cig1 and Cig2 B-type cyclins in the fission yeast cell
      cycle.
AB  - In this report, we describe the cloning and characterization of a B-type cyclin,
      Cig2 from the fission yeast Schizosaccharomyces pombe. The cig2 gene encodes a 45
      kDa protein that is most similar to a previously identified B-type cyclin in S.
      pombe, Cdc13. Deletion of cig2 had no observable effect on cell viability or
      progression through the cell cycle. Strains carrying the cig2 null allele do,
      however, exhibit an enhanced ability to undergo conjugation relative to a wild
      type strain. The cig2 transcript was found to undergo periodic oscillation during
      the cell cycle, peaking at the G1/S-phase boundary. We have investigated the
      relationship between Cig2 and the other B-type cyclins, Cig1 and Cdc13, in the
      fission yeast. We found that cells carrying disruptions of both the cig1 and cig2
      genes contain multiple nuclei with a 1C DNA content, suggesting that they are
      delayed in progression through the G1 phase of the cell cycle. The phenotype of
      this double mutant suggests that there is a delay in septum formation, possibly
      as a result of defective nuclear separation.

PMID- 8264645
TI  - Developmental stage-specific regulation of atrial natriuretic factor gene
      transcription in cardiac cells.
AB  - Cardiac myocytes undergo a major genetic switch within the first week of
      postnatal development, when cell division ceases terminally and many cardiac
      genes are either activated or silenced. We have developed stage-specific
      cardiocyte cultures to analyze transcriptional control of the rat atrial
      natriuretic factor (ANF) gene to identify the mechanisms underlying tissue
      specific and developmental regulation of this gene in the heart. The first 700 bp
      of ANF flanking sequences was sufficient for cardiac muscle- and stage-specific
      expression in both atrial and ventricular myocytes, and a cardiac muscle-specific
      enhancer was localized between -136 and -700 bp. Deletion of this enhancer
      markedly reduced promoter activity in cardiac myocytes and derepressed ANF
      promoter activity in nonexpressing cells. Two distinct domains of the enhancer
      appeared to contribute differentially to cardiac specificity depending on the
      differentiation stage of the myocytes. DNase I footprinting of the enhancer
      domain active in differentiated cells revealed four putative regulatory elements
      including an A+T-rich region and a CArG element. Deletion mutagenesis and
      promoter reconstitution assays revealed an important role for the CArG-containing
      element exclusively in cardiac cells, where its activity was switched on in
      differentiated myocytes. Transcriptional activity of the ANF-CArG box correlated
      with the presence of a cardiac- and stage-specific DNA-binding complex which was
      not recognized by the c-fos serum response element. Thus, the use of this in
      vitro model system representing stage-specific cardiac development unraveled the
      presence of different regulatory mechanisms for transcription of the ANF gene
      during cardiac differentiation and may be useful for studying the regulatory
      pathways of other genes that undergo switching during cardiac myogenesis.

PMID- 8264646
TI  - MGSA/GRO transcription is differentially regulated in normal retinal pigment
      epithelial and melanoma cells.
AB  - We have characterized constitutive and cytokine-regulated MGSA/GRO alpha, -beta,
      and -gamma gene expression in normal retinal pigment epithelial (RPE) cells and a
      malignant melanoma cell line (Hs294T) to discern the mechanism for MGSA/GRO
      constitutive expression in melanoma. In RPE cells, constitutive MGSA/GRO alpha, 
      beta, and -gamma mRNAs are not detected by Northern (RNA) blot analysis although
      nuclear runoff experiments show that all three genes are transcribed. In Hs294T
      cells, constitutive MGSA/GRO alpha expression is detectable by Northern blot
      analysis, and the level of basal MGSA/GRO alpha transcription is 8- to 30-fold
      higher than in RPE cells. In contrast, in Hs294T cells, basal MGSA/GRO beta and 
      gamma transcription is only twofold higher than in RPE cells and no beta or gamma
      mRNA is detected by Northern blot. These data suggest that the constitutive
      MGSA/GRO alpha mRNA in Hs294T cells is due to increased basal MGSA/GRO alpha gene
      transcription. The cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha
      (TNF alpha) significantly increase the mRNA levels for all three MGSA/GRO
      isoforms in Hs294T and RPE cells, and both transcriptional and
      posttranscriptional mechanisms are operational. Nuclear runoff assays indicate
      that in RPE cells, a 1-h IL-1 treatment induces a 10- to 20-fold increase in
      transcription of MGSA/GRO alpha, -beta and -gamma but only a 2-fold increase in
      Hs294T cells. Similarly, chloramphenicol acetyltransferase (CAT) reporter gene
      analysis using the MGSA/GRO alpha, -beta, and -gamma promoter regions
      demonstrates that IL-1 treatment induces an 8- to 14-fold increase in CAT
      activity in RPE cells but only a 2-fold increase in Hs294T cells. The effect of
      deletion or mutation of the MGSA/GRO alpha NF-kappa B element, combined with data
      from gel mobility shift analyses, indicates that the NF-kappa B p50/p65
      heterodimer in RPE cells plays an important role in IL-1- and TNF alpha-enhanced
      gene transcription. In Hs294T cells, gel shift analyses indicate that IL-1 and
      TNF alpha induce NF-kappa B complex formation; however, transactivation does not
      occur, suggesting that subtle differences in the NF-kappa B complexes may result
      in the inability of the cytokines IL-1 and TNF alpha to activate transcription of
      the MGSA/GRO genes. IL-1 and TNF alpha posttranscriptionally regulate MGSA/GRO
      mRNA levels in both cell types. In Hs294T cells, IL-1 increases the half-life of
      MGSA/GRO alpha from 15 min to 6 h (a 24-fold increase in half-life). These data
      indicate that IL-1 and TNF alpha transcriptionally and posttranscriptionally
      regulate MGSA/GRO alpha, -beta, and -gamma mRNA levels in RPE cells, while in
      Hs294T cells, the major effect of IL-1 and TNF alpha is on mRNA stability.

PMID- 8264647
TI  - Functional analysis of the V gamma 3 promoter of the murine gamma delta T-cell
      receptor.
AB  - The initial day 14 wave of fetal thymocytes express a gamma delta T-cell receptor
      (TCR). This surface TCR is generated by preferential rearrangement of V gamma 3
      and V delta 1 recombination segments. To delineate the role of regulatory
      sequences in this expression, we have analyzed the V gamma 3 promoter control
      region under the regulation of its cognate C gamma 1 enhancer. Transcription
      initiates 25 bases downstream from a TATTAA sequence at a consensus initiator
      motif. The minimal 5' promoter sequences supporting expression by transient
      analysis extend -243 nucleotides from the +1 start site. Three regulatory
      sequences in this region have been defined by deletion and mutagenesis: a
      consensus CTF/NF-1 site at -55, an Ets homology sequence at -65, and a
      degenerate, but crucial, SP-1 site at -100. The presence of additional sequences
      downstream of the start site which extend through the leader intron were
      necessary for expression. In contrast to other TCR or immunoglobulin variable
      regions, one or more strong upstream suppressor sequences resembling silencer
      elements have been observed. A 311-bp fragment, positions -586 to -897, exhibited
      strong repressing activity regardless of orientation when placed upstream of
      heterologous promoters.

PMID- 8264648
TI  - Functional significance of lysine 1423 of neurofibromin and characterization of a
      second site suppressor which rescues mutations at this residue and suppresses
      RAS2Val-19-activated phenotypes.
AB  - Lysine 1423 of neurofibromin (neurofibromatosis type I gene product [NF1]) plays
      a crucial role in the function of NF1. Mutations of this lysine were detected in
      samples from a neurofibromatosis patient as well as from cancer patients. To
      further understand the significance of this residue, we have mutated it to all
      possible amino acids. Functional assays using yeast ira complementation have
      revealed that lysine is the only amino acid that produced functional NF1.
      Quantitative analyses of different mutant proteins have suggested that their
      GTPase-activating protein (GAP) activity is drastically reduced as a result of a
      decrease in their Ras affinity. Such a requirement for a specific residue is not
      observed in the case of other conserved residues within the GAP-related domain.
      We also report that another residue, phenylalanine 1434, plays an important role
      in NF1 function. This was first indicated by the finding that defective NF1s due
      to an alteration of lysine 1423 to other amino acids can be rescued by a second
      site intragenic mutation at residue 1434. The mutation partially restored GAP
      activity in the lysine mutant. When the mutation phenylalanine 1434 to serine was
      introduced into a wild-type NF1 protein, the resulting protein acquired the
      ability to suppress activated phenotypes of RAS2Val-19 cells. This suppression,
      however, does not involve Ras interaction, since the phenylalanine mutant does
      not stimulate the intrinsic GTPase activity of RAS2Val-19 protein and does not
      have an increased affinity for Ras proteins.

PMID- 8264649
TI  - A mutation in the second largest subunit of TFIIIC increases a rate-limiting step
      in transcription by RNA polymerase III.
AB  - In previous studies, we have shown that the PCF1-1 mutation of Saccharomyces
      cerevisiae suppresses the negative effect of a tRNA gene A block promoter
      mutation in vivo and increases the transcription of a variety of RNA polymerase
      III genes in vitro. Here, we report that PCF1 encodes the second largest subunit
      of transcription factor IIIC (TFIIIC) and that the PCF1-1 mutation causes an
      amino acid substitution in a novel protein structural motif, a tetratricopeptide
      repeat, in this subunit. In agreement with the nature of the mutation, in vitro
      transcription studies with crude extracts indicate that PCF1-1 facilitates the
      rate-limiting step in transcription, namely, the recruitment of TFIIIB to the
      template. Additionally, biochemical fractionation of wild-type and mutant cell
      extracts shows that PCF1-1 increases the amount of the 70-kDa TFIIIB subunit
      detectable by Western (immunoblot) analysis in purified TFIIIB fractions and the
      transcription activity of a TFIIIB" fraction containing the 90-kDa subunit of
      this factor. We suggest that the effect of PCF1-1 on TFIIIB activity in vitro is
      a consequence of its increased rate of recruitment in vivo.

PMID- 8264650
TI  - MDS1, a dosage suppressor of an mck1 mutant, encodes a putative yeast homolog of
      glycogen synthase kinase 3.
AB  - The yeast gene MCK1 encodes a serine/threonine protein kinase that is thought to
      function in regulating kinetochore activity and entry into meiosis. Disruption of
      MCK1 confers a cold-sensitive phenotype, a temperature-sensitive phenotype, and
      sensitivity to the microtubule-destabilizing drug benomyl and leads to loss of
      chromosomes during growth on benomyl. A dosage suppression selection was used to
      identify genes that, when present at high copy number, could suppress the cold
      sensitive phenotype of mck1::HIS3 mutant cells. Several unique classes of clones
      were identified, and one of these, designated MDS1, has been characterized in
      some detail. Nucleotide sequence data reveal that MDS1 encodes a serine/threonine
      protein kinase that is highly homologous to the shaggy/zw3 kinase in Drosophila
      melanogaster and its functional homolog, glycogen synthase kinase 3, in rats. The
      presence of MDS1 in high copy number rescues both the cold-sensitive and the
      temperature-sensitive phenotypes, but not the benomyl-sensitive phenotype,
      associated with the disruption of MCK1. Analysis of strains harboring an mds1
      null mutation demonstrates that MDS1 is not essential during normal vegetative
      growth but appears to be required for meiosis. Finally, in vitro experiments
      indicate that the proteins encoded by both MCK1 and MDS1 possess protein kinase
      activity with substrate specificity similar to that of mammalian glycogen
      synthase kinase 3.

PMID- 8264651
TI  - Cooperative binding of Ets-1 and core binding factor to DNA.
AB  - Two phorbol ester-inducible elements (beta E2 and beta E3) within the human T
      cell receptor beta gene enhancer each contain consensus binding sites for the Ets
      and core binding factor (CBF) transcription factor families. Recombinant Ets-1
      and purified CBF bound individually to beta E2 and beta E3, in which the Ets and
      core sites are directly adjacent. In this report, we show that CBF and Ets-1 bind
      together to beta E2 and beta E3 and that Ets-1-CBF-DNA complexes are favored over
      the binding of either protein alone to beta E2. Formation of Ets-1-CBF-DNA
      complexes increased the affinity of Ets-1-DNA interactions and decreased the rate
      of dissociation of CBF from DNA. Ets-1-CBF-DNA complexes were not observed when
      either the Ets or core site was mutated. The spatial requirements for the
      cooperative interaction of Ets-1 and CBF were analyzed by oligonucleotide
      mutagenesis and binding site selection experiments. Core and Ets sites were
      coselected, and there appeared to be little constraint on the relative
      orientation and spacing of the two sites. These results demonstrate that CBF and
      Ets-1 form a high-affinity DNA-binding complex when both of their cognate sites
      are present and that the relative spacing and orientation of the two sites are
      unimportant. Ets and core sites are found in several T-cell-specific enhancers,
      suggesting that this interaction is of general importance in T-cell-specific
      transcription.

PMID- 8264652
TI  - Loss of thrombospondin transcriptional activity in nickel-transformed cells.
AB  - mRNA from normal Chinese hamster embryo (CHE) cells was transcribed to cDNA and
      subtracted with an excess of mRNA from Chinese hamster embryo cells transformed
      by nickel compounds. Here we report the recovery of a sequence found to be highly
      homologous to the mouse thrombospondin 1 gene that was obtained by this
      subtraction procedure. Since thrombospondin is antiangiogenic, cancer cells
      expressing high levels of thrombospondin cannot grow in vivo because capillaries
      will not proliferate to cells secreting thrombospondin. To examine expression of
      thrombospondin, normal CHE cells were stained with monoclonal antibodies to human
      thrombospondin. The protein was present abundantly in the cytoplasm of normal
      cells but at greatly reduced levels in Ni-transformed cells. Analysis of mRNA by
      Northern (RNA) blot revealed transcripts in normal cells but little
      thrombospondin mRNA in Ni-transformed cells. Loss of thrombospondin mRNA
      expression was related to Ni treatment rather than transformation, since Ni
      resistant cells also exhibited fewer thrombospondin transcripts than did wild
      type cells. Digestion of genomic DNA with various combinations of restriction
      enzymes revealed thrombospondin gene patterns that were identical in both cell
      types, suggesting that there were no major deletions or rearrangements of the
      gene in the nickel-transformed cells. The inactivation of the thrombospondin gene
      was further investigated by analyzing the promoter activity of this gene linked
      to a chloramphenicol acetyltransferase (CAT) reporter plasmid that was
      transfected into normal and Ni-transformed cells. The CAT activity in normal
      cells was significantly higher than in Ni-transformed cells, suggesting that the
      promoter region of thrombospondin was less efficiently transcribed in Ni
      transformed cells. We studied the consequences of enhanced expression of the
      retinoblastoma (Rb) gene, a known tumor suppressor gene, on CAT transcription
      driven by the human thrombospondin promoter. Cotransfection of an expression
      vector containing the mouse Rb gene greatly enhanced the transcription from the
      thrombospondin promoter such that the expression was higher in normal cells than
      in transformed cells.

PMID- 8264653
TI  - Evidence for a role of the Drosophila melanogaster suppressor of sable gene in
      the pre-mRNA splicing pathway.
AB  - Recessive mutations of the Drosophila melanogaster suppressor of sable [su(s)]
      gene result in elevated accumulation of RNA from vermilion (v) mutant alleles
      that have an insertion of the 7.5-kb retrotransposon 412 in the first exon of the
      v gene. During transcription of such a v mutant gene, the 412 sequences are
      incorporated into the primary transcripts and are subsequently removed by
      splicing at cryptic sites within 412 sequences. In a su(s)+ background, the level
      of these unusually spliced transcripts is exceedingly low, and su(s) mutations
      increase their accumulation. We previously proposed that v RNA levels are
      elevated in su(s) mutants because of increased recognition of the cryptic splice
      sites, and the aim of this study was to test this hypothesis. We generated a v
      mutant derivative with a smaller 412 insertion, introduced alterations into the
      412-associated splice sites, and examined the effect of su(s) mutations on
      expression of these derivatives after germ line transformation. To increase
      overall expression levels, the v promoter was replaced with the stronger
      Metallothionein (Mtn) gene promoter. We found that transformants bearing a v
      derivative with 480 bp of 412 sequences accumulate both transcripts, with 412
      sequences spliced out and transcripts that retain 412 sequences. Mutations of
      su(s) increase the levels of both transcript classes without affecting the
      relative amounts of the two forms. Strikingly, replacement of the cryptic 5'
      splice sites with a 5' consensus produces the same effect as, and eliminates the
      response to, a su(s) mutation. In addition, we demonstrated that mutations of
      su(s) lead to increased accumulation of v transcripts even when the previously
      identified cryptic 412 5' and 3' splice sites were destroyed and that other
      cryptic splice sites reside within Mtn and 412 sequences. These results indicate
      that the v mutant transcripts are stabilized by assembly of the 412 sequences
      into splicing complexes and support the hypothesis that splicing complexes more
      readily assemble on cryptic splice sites in su(s) mutants.

PMID- 8264654
TI  - Transcriptional up-regulation of the mouse cytosolic glutathione peroxidase gene
      in erythroid cells is due to a tissue-specific 3' enhancer containing
      functionally important CACC/GT motifs and binding sites for GATA and Ets
      transcription factors.

PMID- 8264655
TI  - Distinct domains of antizyme required for binding and proteolysis of ornithine
      decarboxylase.
AB  - Selective degradation by proteasomes of ornithine decarboxylase, the initial
      enzyme in polyamine biosynthesis, is mediated by the polyamine-inducible protein
      antizyme. Antizyme binds to a region near the N terminus of ornithine
      decarboxylase (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-3562, 1992). This
      interaction induces a conformational change in ornithine decarboxylase that
      exposes its C terminus and inactivates the enzyme (X. Li and P. Coffino, Mol.
      Cell. Biol. 13:1487-1492, 1993). Here we show that the C-terminal half of
      antizyme alone can inactivate ornithine decarboxylase and alter its conformation,
      but it cannot direct degradation of the enzyme, either in vitro or in vivo. A
      portion of the N-terminal half of antizyme must be present to promote
      degradation.

PMID- 8264656
TI  - Characterization of a single strong tissue-specific enhancer downstream from the
      three human genes encoding placental lactogen.
AB  - The human genes coding for growth hormone (hGH) and placental lactogen
      (choriosomatomammotropic hormone [hCS]) are clustered on chromosome 17 in the
      following order: 5' hGH-N hCS-L hCS-A hGH-V hCS-B 3'. So far, a single placenta
      specific enhancer has been identified in the locus, 2 kb downstream from the hCS
      B gene, and shown to comprise one in vitro binding site for a nuclear protein. We
      here provide evidence that the hCS-B enhancer is more complex: (i) protection
      against DNase I digestion in the 3' flanking region of the hCS-B gene reveals
      four binding sites (DF-1, DF-2, DF-3, and DF-4) for nuclear proteins from either
      placental or HeLa cells, and (ii) placenta-specific enhancer activity can be
      fully exerted in transient expression experiments by a 126-bp fragment comprising
      the DF-3 and DF-4 protein-binding sites. By dissecting this region, we show that
      enhancer activity is mediated by a synergy between DF-3 and DF-4. Competitions
      with various oligonucleotides in footprinting and gel retardation experiments
      indicate that the same protein or set of proteins, different in HeLa and placenta
      cell nuclei, interacts with sites DF-2, DF-3, and DF-4. We also studied the
      regions of the hCS-L and hCS-A genes which are highly similar to the hCS-B
      enhancer. Although they each present the same four protein-binding sites, they
      exhibit only minor enhancer activity.

PMID- 8264657
TI  - INSIGHT: subunit functions of the steroid/thyroid receptor family.

PMID- 8264658
TI  - Human progesterone receptor A form is a cell- and promoter-specific repressor of
      human progesterone receptor B function.
AB  - Two distinct isoforms of the human progesterone receptor (hPR-A and hPR-B) have
      been identified previously. They differ only in that hPR-B contains an additional
      164 amino acids at the amino terminus. Among various species these two forms
      arise as a result of either alternate initiation of translation from the same
      mRNA or by transcription from alternate promoters within the same gene. In order
      to understand the reason for their existence, we studied the transcriptional
      capacity of these individual receptors and observed that their activity was
      influenced strongly by cell and promoter context. More surprising was the
      observation that in promoter and cell contexts where hPR-A was inactive, it acted
      as a potent trans-dominant repressor of hPR-B-mediated transcription. This event
      occurred at substoichiometric concentrations of hPR-A and was hormone dependent.
      Human PR-A was not a general repressor of ligand-mediated transcription, as it
      had no effect on vitamin D receptor function. Interestingly, hPR-A but not hPR-B
      was capable of a similar inhibition of glucocorticoid, androgen, and
      mineralocorticoid receptor-mediated gene transcription. This suggests a specific
      role for the hPR-A isoform in this regulatory process. The trans-dominant effects
      of hPR-A were induced also by the antiprogestins ZK112993 and ZK98299 and a DNA
      binding defective hPR-A mutant, suggesting that the inhibitory function of hPR-A
      does not require DNA binding. The dual role of hPR-A as an activator or repressor
      of transcription defines a potential mechanism by which cells can generate
      dissimilar responses to a single hormone and provides a molecular explanation for
      the existence of two distinct forms of the hPR.

PMID- 8264659
TI  - Transcriptional activation by the estrogen receptor requires a conformational
      change in the ligand binding domain.
AB  - The estrogen receptor (ER) is a strong hormone-inducible transcription factor
      that regulates the expression of many genes. It was shown for the human
      progesterone receptor that the binding of hormone causes distinct conformational
      changes in the ligand binding domain (LBD) and that these changes in LBD
      conformation are crucial for events after DNA binding. We now show that
      conformational changes in the LBD of the human ER are a prerequisite for trans
      activation. Under the appropriate conditions ER binds to its response element and
      activates transcription only in the presence of ligand. Binding of the ligand
      causes changes in the conformation of the LBD. Antihormones induce distinct
      conformational changes, the differences between the conformations lying in the
      carboxy-terminal end of the receptor. Changing the experimental conditions
      results in a receptor that can bind to DNA and activate transcription in a ligand
      independent manner. Under these conditions the LBD has a transcriptionally active
      conformation in the absence of ligand. Taken together, our data indicate that the
      conformational change induced by ligand is required for converting a receptor to
      the transcriptionally active form.

PMID- 8264660
TI  - Phorbol ester stimulates the synthesis and secretion of brain natriuretic peptide
      from neonatal rat ventricular cardiocytes: a comparison with the regulation of
      atrial natriuretic factor.
AB  - During left ventricular hypertrophy, brain natriuretic peptide (BNP) and atrial
      natriuretic factor (ANF) mRNA levels increase, possibly due to stretch-induced
      activation of protein kinase C. Phorbol ester treatment of primary cultures of
      neonatal rat ventricular cardiocytes represents an in vitro model of hypertrophic
      cell growth and has previously been shown to stimulate ANF synthesis and
      secretion. Using this model, we studied the synthesis and secretion of BNP to
      determine whether its regulation in cardiac cells is similar to ANF. Addition of
      10(-7) M phorbol 12-myristate 13-acetate (PMA) resulted in a 3- to 4-fold
      increase in immunoreactive BNP (irBNP) secretion 24-48 h after treatment. Over a
      concentration range of 10(-8)-10(-6) M, PMA increased irBNP secretion to
      equivalent levels. Another phorbol ester agonist, phorbol 12,13-didecanoate,
      stimulated irBNP secretion, while the inactive analog 4 alpha-phorbol 12,13
      didecanoate had no effect. Inhibition of protein kinase C (PKC) with 10(-8) M
      staurosporine decreased basal secretion of irBNP 60% and prevented PMA induction
      of irBNP, whereas both stimulated and basal secretion of ANF were minimally
      affected. BNP mRNA increased 6-fold by 3 h of PMA treatment and remained elevated
      above control levels for 48 h. Staurosporine prevented the increase in BNP mRNA.
      To determine whether PKC or a PKC-dependent pathway was involved in persistent
      stimulation of BNP and ANF in cells chronically treated with PMA, ventricular
      cardiocytes were treated with PMA for 24 h, followed by PMA plus 10(-8) M
      staurosporine for 24 h. BNP mRNA was reduced to control levels, while ANF mRNA
      was reduced by an average of 20%. To test whether mRNA stability was involved in
      the differential effect of chronic phorbol ester treatment, cardiocytes were
      treated with the protein synthesis inhibitor cycloheximide (20 micrograms/ml).
      BNP mRNA levels were stimulated as early as 30 min after treatment, but ANF mRNA
      remained unaffected. Cycloheximide also potentiated PMA's effect on BNP mRNA
      after 1.5, 9.5, and 24 h of treatment. To test whether a transcriptional
      mechanism was involved in the stimulation of BNP mRNA by PMA, cells were treated
      with the inhibitor actinomycin D (5 micrograms/ml) for 24 h in the presence of
      PMA. Actinomycin D reduced the stimulatory effect of PMA on BNP mRNA.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8264661
TI  - Identification of a cis-regulatory element and a thyroid-specific nuclear factor
      mediating the hormonal regulation of rat thyroid peroxidase promoter activity.
AB  - The mechanism for hormonal regulation of rat thyroperoxidase (rTPO) gene
      transcription in rat FRTL-5 thyroid cells has been investigated. Transient
      transfection experiments demonstrate that the minimal rTPO promoter that confers
      thyroid-specific expression also confers responsiveness to TSH and insulin. TSH
      induces a 7-fold increase in promoter activity, and the induction is detected
      almost immediately after the addition of the hormone. Insulin also stimulates TPO
      promoter activity, but the effect of this hormone is weaker and slower than that
      of TSH. The effect of TSH in increasing TPO promoter activity is mimicked by the
      cAMP agonist forskolin. The calcium-protein kinase C pathway is also involved in
      the regulation of the rTPO promoter activity, since a calcium ionophore (A23187)
      and phorbol esters [12-O-tetradecanoyl-phorbol-13-acetate (TPA)] inhibit it
      quickly. These data indicate that the region of the rTPO promoter used here
      contains the DNA signals necessary for its hormonal regulation. Protein-DNA
      binding studies show that the thyroid-specific nuclear protein TTF-2, which binds
      to the rTPO promoter, is induced by TSH and forskolin, and this effect is clearly
      observable as early as 5 h post induction. Moreover, the DNA binding activity of
      TTF-2 is inhibited by both A23187 and TPA. Heterologous promoter constructs
      containing four, eight, or 12 tandem repeats of an oligonucleotide that includes
      the TTF-2 binding site increase their activity in response to TSH, forskolin, and
      insulin, while the the presence of A23187 or TPA inhibits their activity. These
      data indicate that the TTF-2 protein plays an important role in the hormonal
      control of thyroid-specific transcription.

PMID- 8264662
TI  - Stabilization of the vitamin D receptor in rat osteosarcoma cells through the
      action of 1,25-dihydroxyvitamin D3.
AB  - A regulatory mechanism for the vitamin D receptor (VDR) in rat osteosarcoma cells
      (ROS 17/2.8) is stabilization of the receptor through binding of its ligand, 1,25
      dihydroxyvitamin D3 [1,25-(OH)2D3]. Increased transcription of the gene encoding
      VDR does not occur upon treatment of these osteoblast-like cells with 1,25
      (OH)2D3. When 10 nM 1,25-(OH)2D3 was administered to confluent cultures of ROS
      17/2.8 cells, no change in receptor mRNA was detected, as measured by a
      ribonuclease protection assay. VDR abundance was measured using an
      immunoradiometric assay at varying time points within a 24-h period after 1,25
      (OH)2D3 treatment. Receptor protein levels increased rapidly and continued to
      rise over 24 h. By 2 h, the level of receptor increased 2.5-fold, achieving a
      maximum level of 8-fold above the baseline at 18 h. The half-life of the receptor
      protein is 2 h in the absence of hormone, as determined by blockage of
      translation in cycloheximide-treated cells. In the presence of hormone, however,
      receptor levels were unchanged for at least 6 h. The administration of 1,25
      (OH)2D3 stabilizes the receptor, thereby resulting in its accumulation in ROS
      17/2.8 cells.

PMID- 8264663
TI  - Dominant negative inhibition by mutant thyroid hormone receptors is thyroid
      hormone response element and receptor isoform specific.
AB  - The heterogeneity of tissue-specific manifestations of generalized resistance to
      thyroid hormone (GRTH) could result from differential interactions between the
      mutant thyroid hormone (T3) receptor-beta (TR beta) on T3 response elements
      (TREs) in different T3-responsive genes. To explore this hypothesis, the mutant
      TR beta associated with kindred A, P448H; a TR beta mutant, P448L; and a
      comparable TR alpha mutant (P398H) were tested for intrinsic function and for
      inhibition of wild-type TR alpha- and -beta-induced expression from four
      structurally distinct TREs, the rGH ABC*, the rGH palindrome (PAL), the rat malic
      enzyme (ME), and the chicken lysozyme silencer F2 (F2). The relative function of
      the mutants was similarly reduced on the four TREs studied and was T3
      concentration dependent. The TR alpha mutant retained the intrinsically greater
      potency characteristic of this isoform, but remained impaired with respect to
      wild-type TR alpha even at 500 nM T3. In general, dominant negative inhibition of
      wild-type TR alpha and -beta function was dependent upon the T3 concentration, as
      expected from the decreased affinity for ligand conferred by this mutation. A T3
      concentration sufficient to relieve the inhibition of wild-type TR function on
      the ABC*, PAL, and ME TREs (50 nM) had no effect on inhibition of the F2 TRE by
      the mutant TRs. Receptor isoform preferential inhibition was observed on the
      ABC*, PAL, and ME TREs by the mutant TRs. Thus, both TRE structure and the
      isoform of endogenously active receptor could determine the degree of inhibition
      of a specific gene in GRTH individuals. Further, the lack of dominant negative
      potentials does not explain the absence of TR alpha mutations in GRTH kindreds.

PMID- 8264664
TI  - Retinoic acid receptors and retinoid X receptor-alpha down-regulate the
      transforming growth factor-beta 1 promoter by antagonizing AP-1 activity.
AB  - Overexpression of the multifunctional growth factor transforming growth factor
      beta 1 (TGF beta 1) has been connected to numerous diseases in human. TGF beta 1
      expression is largely governed by three AP-1 binding sites located in two
      different promoters of this gene. We have examined the ability of retinoid
      receptors to inhibit the activity of the two promoters (especially the promoter
      1) by cotransfection assays in the hepatocellular carcinoma cell line HepG2. When
      the TGF beta 1 promoter activity is induced by 12-O-tetradecanoyl phorbol13
      acetate (an activator of AP-1-controlled gene transcription), this activity can
      be strongly repressed by retinoic acid receptor-alpha (RAR alpha), RAR beta, or
      retinoid X receptor-alpha (RXR alpha) as well as other members of the nuclear
      receptor family. Repression was hormone dependent and a function of receptor
      concentration. Heterodimerization of RAR alpha or RAR beta with RXR alpha did not
      modify the inhibition activities of these receptors, indicating that heterodimer
      formation is not required for antagonizing of AP-1 activity. On further examining
      the anti-AP-1 activity of RXR alpha we observed that three different AP-1
      controlled promoters (TGF beta 1, collagenase, and cFos) can be inhibited. Using
      gel shift assays, we demonstrated that RXR alpha inhibits Jun and Fos DNA binding
      and that 9-cis RA enhances this inhibition, suggesting that a mechanism involving
      direct protein-protein interaction between RXR and AP-1 components mediates the
      inhibitory effect observed in vivo. Transfection analyses with RXR alpha point
      mutations revealed that residues L422, C432, and, to a lesser extent, residues
      L418 and L430, are involved in ligand-induced anti-AP1 activity of RXR alpha in
      vivo. Thus both types of retinoid receptors can inhibit AP-1-activated promoters,
      including the TGF beta 1 gene promoter, via a mechanism that involves protein
      protein interaction.

PMID- 8264665
TI  - Corticotropin-releasing factor activates c-fos, NGFI-B, and corticotropin
      releasing factor gene expression within the paraventricular nucleus of the rat
      hypothalamus.
AB  - Studies examining the regulation of hypothalamic CRF biosynthesis have provided
      substantial information regarding the relevance of this peptide in neuroendocrine
      homeostasis. However, the consequences of elevated CRF levels within the
      mammalian central nervous system on regulation of CRF production within the
      paraventricular nucleus (PVN) of the hypothalamus remain unclear. The expression
      of the immediate early gene c-fos has been used and validated as a marker for
      neural systems activated by a variety of extracellular stimuli and has been
      especially useful when examining activation of central neuroendocrine systems
      such as those involved in the response to stressful stimuli. The present study
      investigates the effects of injecting CRF into the lateral ventricle of conscious
      rats, firstly on the expression of two separate immediate early genes, c-fos and
      NGFI-B within the hypothalamic PVN, and secondly on the expression of CRF mRNA
      itself, as determined by quantitative in situ hybridization. Expression of Fos
      protein was also examined by immunohistochemical techniques.
      Intracerebroventricular (icv) injection of CRF increased the gene expression of
      both c-fos and NGFI-B in the parvocellular division of the PVN 30 min after
      injection. Fos immunoreactivity increased in this same region between 30-60 min,
      whereas expression of the CRF gene itself increased 2-fold 60 min after injection
      and remained elevated 2 h after treatment. A positive hybridization signal for
      CRF was observed over Fos-immunoreactive neurons within the parvocellular
      division of the PVN. Finally, we observed that all CRF-induced changes in gene
      expression were abolished by pretreatment with the competitive CRF antagonist
      alpha-helical CRF-(9-41). The time-related changes in expression of the genes
      measured imply that the expression of both c-fos and NGFI-B occurs before a
      significant increase in the expression of CRF. The results also suggest that CRF
      may act in a positive manner to regulate its own biosynthesis.

PMID- 8264666
TI  - A multiple primer pairs polymerase chain reaction for the detection of human
      genital papillomavirus types.
AB  - We describe a polymerase chain reaction (PCR) based on the simultaneous detection
      of multiple strains of papillomavirus in a single reaction tube. This PCR method
      was specific and sensitive. We have validated this multiplex procedure on a
      collection of typed cervical biopsies specimens, and applied it to the detection
      of viruses in some clinical samples.

PMID- 8264667
TI  - Oligonucleotide probe determination of tetracycline-resistant bacteria isolated
      from catfish ponds.
AB  - Oligonucleotide probes for class A, B and C tetracycline resistance determinants
      were synthesized and tested individually and in combination for hybridization
      with Gram-negative isolates previously characterized by restriction fragment DNA
      probes. Similar hybridization patterns were observed with either probe type. Gram
      negative catfish pond bacteria were characterized by these oligonucleotide
      probes. The most common bacteria were Plesiomonas shigelloides (47.7%), Aeromonas
      hydrophila (28.8%) and Citrobacter freundii (13.3%). The class A (46.4%)
      tetracycline resistance determinant was more prevalent than B (19.8%) and C
      (0.3%). Some tetracycline-resistant isolates of each species, including most A.
      hydrophila (62.1%) isolates, failed to hybridize with any of the probes.

PMID- 8264669
TI  - Comparison of polymerase chain reaction and culture techniques for detection of
      Chlamydia trachomatis.
AB  - The aim of this study was to compare culture and polymerase chain reaction
      techniques in detection of Chlamydia trachomatis in clinical specimens. Two
      hundred clinical specimens previously examined for C. trachomatis by culture were
      analysed blindly by polymerase chain reaction. A 144 bp fragment of DNA from the
      MOMP of C. trachomatis was amplified. In addition, a 250 bp segment of beta
      globin gene was amplified as an internal control. In 27 culture negative
      specimens, the beta-globin amplicon was not detected. Of the 173 specimens
      assessable by PCR, 24 (13.8%) were positive by both methods. Four specimens were
      positive by PCR and negative by culture. Three were collected post-antibiotic
      treatment; two were from previous culture-proven chlamydia infection suggestive
      of the presence of DNA of non-viable organisms, and one case was toxic by
      culture. No specimen was positive by culture and negative by PCR. Overall PCR
      when compared to culture had a sensitivity of 100% and specificity of 97.3% with
      positive and negative predictive values of 85.7% and 100%, respectively. PCR is
      especially useful when culture results can not be confirmed due to toxicity,
      inadequate transport or insufficient specimen collected.

PMID- 8264668
TI  - The nucleotide sequence of the 5'-untranslated region of bovine viral diarrhoea
      virus: its use as a probe in rapid detection of bovine viral diarrhoea viruses
      and border disease viruses.
AB  - A 289 bp cDNA fragment from the 5'-untranslated region (UTR) of 16 bovine viral
      diarrhoea virus (BVDV) isolates was amplified by reverse transcription and
      polymerase chain reaction, and sequenced by dideoxy DNA sequencing. The sequence
      showed greater than 90% homology between the isolates and BVDV NADL in this
      region, and greater than 97% homology within a 72 base sub-region (nt 314-386).
      The 289 bp fragment was then used as a probe for rapid detection of BVDV and
      border disease virus (BDV) from cell culture samples by dot-blot hybridization.
      This probe hybridized to 100% of BVDV isolates (n = 78) and 100% of BDV isolates
      (n = 9), but not to the uninfected BT cells or other bovine infectious agents. A
      shorter probe from the more conserved sub-region also was tested for
      hybridization with some of the isolates, and the results were similar to those
      using the longer probe. These results suggest that the 5'-UTR is highly conserved
      among BVDV and BDV isolates, and may be used as a potential probe for rapid
      detection of BVDV and BDV in clinical and cell culture samples from cattle and
      sheep.

PMID- 8264670
TI  - Sensitive and quantitative detection of PCR-amplified HIV-1 DNA products by an
      enzyme linked immunoassay following solution hybridization with two differently
      labelled oligonucleotide probes.
AB  - We have developed and evaluated an ELISA-based detection method for PCR-amplified
      HIV-1 DNA. The assay uses two oligonucleotide probes which are end-labelled at
      the 5'-end with biotin or digoxigenin, respectively. Upon solution hybridization
      of these probes which react with the same strand of amplified DNA product, the
      formed hybrids are bound to avidin-coated wells of a microtitre plate and
      detected by horseradish peroxidase-labelled antibodies directed against digoxigen
      and 3, 3', 5, 5'-tetramethylbenzidine as substrate. Factors critical for a high
      signal-to-noise ratio were the use of serum as blocking agent, the amount of
      biotin-labelled and digoxigenin-labelled oligonucleotide probes present in a
      reaction and the inactivation of Taq DNA polymerase. The method has a detection
      limit of 1-3 pg of amplified DNA and is quantitative in a range extending from 1
      pg to at least 200 pg. In the background of 1 microgram of total DNA, one single
      stranded copy of HIV-1 DNA can be detected after 35 cycles of amplification. A
      comparison of the ELISA-based detection method with primer extension analysis, a
      method previously shown to reach a similar detection limit, demonstrated complete
      agreement of the results of 118 amplified DNAs. The method proved simple,
      requires only about 3 h, and could easily be adapted to the detection of other
      amplified target DNAs.

PMID- 8264671
TI  - Detection of human rhinovirus RNA in nasal washings by PCR.
AB  - A PCR assay was developed to detect human rhinovirus (HRV) RNA in nasal washings
      from individuals experimentally infected with HRV-39 or HRV strain Hanks. Total
      RNA was purified from samples stored in the presence of vanadyl ribonucleoside
      complex (VRC) by one of two methods: proteinase K digestion followed by multiple
      extractions with phenol/chloroform (PK-PC); or denaturation with guanidinium
      thiocyanate followed by one phenol/chloroform extraction (GTC). The limit of
      detection of HRV in nasal washings spiked with HRV-39 was lower with the GTC
      method (1 TCID50) than with the PK-PC method. In a study of 31 nasal washings
      extracted by the PK-PC method, the sensitivity (93%) and negative predictive
      value (94%) were sub-optimal in comparison to cell culture. In a study of 60
      nasal washings extracted by the GTC method, the number of samples positive by PCR
      (25) exceeded by two the number positive by isolation in cell culture. A GTC
      based method for HRV RNA extraction in nasal washings was superior to a
      proteinase K-phenol/chloroform-based method in regard to sensitivity, consumption
      of reagents, material and time.

PMID- 8264672
TI  - Development of polymerase chain reaction primers to detect Mycoplasma
      hyopneumoniae.
AB  - Mycoplasma hyopneumoniae (Mhp) is the etiologic agent of mycoplasma pneumonia in
      swine. The purpose of this study was to develop a species-specific polymerase
      chain reaction (PCR)-based diagnostic reagent for the identification of Mhp.
      Based upon DNA sequence analysis of a cloned fragment of Mhp DNA, PCR primers
      were constructed and tested against different strains of Mhp, Mycoplasma
      flocculare, other mycoplasma species, and non-Mollicute micro-organisms which
      commonly inhabit the respiratory tracts of swine. A total of 40 field isolates
      from Mhp and four field isolates of M. flocculare have been examined. Positive
      signals were obtained in PCR with Mhp reference strains and all 40 Mhp field
      isolates, but not with other Mollicutes micro-organisms.

PMID- 8264673
TI  - Detection of Tet M and Tet O tetracycline resistance genes by polymerase chain
      reaction.
AB  - Degenerate oligonucleotide primers were used in polymerase chain reaction assays
      to detect tetracycline resistance genes, Tet M and Tet O. Each of 44 clinical
      isolates and eight laboratory strains, representing 20 different species carrying
      either Tet M or Tet O determinants, gave appropriate PCR products with the two
      primer sets. The PCR products hybridized with radiolabelled Tet M or Tet O
      probes. The PCR assay was then used to evaluate vaginal swab specimens from women
      with vaginitis and semen specimens from men with prostatis. Seven of eight
      vaginal samples and five of eight semen samples exhibited PCR products that
      hybridized with the radiolabelled probes, suggesting the presence of Tet M and/or
      Tet O genes. PCR-based detection of Tet M and/or Tet O genes holds promise for
      evaluation of urogenital specimens.

PMID- 8264674
TI  - Chemiluminescent detection of strand displacement amplified DNA from species
      comprising the Mycobacterium tuberculosis complex.
AB  - Strand displacement amplification, a new isothermal in vitro DNA amplification
      technique, was used to amplify target DNA contained within the IS6110 insertion
      element of the species within the Mycobacterium complex (Mycobacterium
      tuberculosis, M. bovis, M. bovis-BCG, M. africanum and M. microti). The target
      nucleic acid sequence is present in approximately ten, two, one, five and five
      copies in M. tuberculosis, M. bovis, M. bovis-BCG, M. africanum and M. microti,
      respectively. Amplified products were detected using a non-isotopic microtitre
      plate assay employing a biotinylated oligodeoxynucleotide probe and an alkaline
      phosphatase conjugated oligodeoxynucleotide probe. Lumiphos 530 was the
      chemiluminescent substrate for alkaline phosphatase. The combination of the
      strand displacement amplification method with this sensitive and rapid (less than
      2 h) detection system resulted in the specific detection of as few as 1-25
      initial IS6110 targets in the five Mycobacterium complex species based on
      signal/noise criteria. Negative results were obtained with eight other
      Mycobacterium species as well as with 32 non-Mycobacterium species.

PMID- 8264675
TI  - Construction of a genetic map telomeric to HLA-A by microsatellite analysis.
AB  - Allele and genotype frequencies of five microsatellites on the short arm of
      chromosome 6 have been determined in 158 subjects from 14 large Italian families,
      using polymerase chain reaction amplification and a non-radioactive method of
      detection. The markers studied were: D6S89, D6S109, D6S105, pLR12 and HLA-F;
      their heterozygosity ranged from 0.65 to 0.78. Two point and three point linkage
      analysis among these markers and HLA-A serological types--available for all the
      studied samples--allowed construction of a partial genetic map telomeric to HLA
      A. Our results may be useful for linkage analysis of genetic disorders mapping on
      this region of 6p.

PMID- 8264676
TI  - Detection of a neurofibromatosis type I (NF1) homologous sequence by PCR:
      implications for the diagnosis and screening of genetic diseases.
AB  - The neurofibromatosis type I (NF1) gene was extensively screened for mutations
      using single strand conformation polymorphism (SSCP) technology. During the
      analysis of the NF1 GAP-related domain, electrophoretically abnormal fragments
      were detected. Direct sequencing of these fragments allowed us to identify the
      presence of a NF1 highly homologous sequence (NF1HHS). A detailed analysis of a
      hybrid panel located this sequence on chromosome 15q24-->qter. An accurate search
      through several data banks demonstrated that this sequence is a new NF1
      homologue. This report shows how it is possible to find homologous sequences at
      random, and subsequently to make wrong interpretations.

PMID- 8264677
TI  - [90th birthday of the Monatsschrift Kinderheilkunde].
AB  - The first issue of the Monatsschrift fur Kinderheilkunde (Monthly Journal of
      Pediatrics) appeared in October 1903 with contributions by leading European
      pediatricians. The editor was Arthur Keller, who remained responsible until 1934.
      As a novelty, the journal contained detailed reviews of world-wide pediatric
      literature. After Keller's death in 1934, Georg Bessau became editor-in-chief for
      the next 10 years. The first issue after the second world war appeared in 1948/49
      and was edited by Hans Kleinschmidt, Gottingen. In 1962 the editorial
      responsibility was transferred to Karl Heinz Schafer, whom joined Hans Ewerbeck
      in 1970. The monthly journal written in German deals with informations for
      pediatricians in children's hospitals and in practices and with scientific
      contributions in all fields of pediatrics and related areas. The present editors
      are Flix Blaker and Werner Schroter. In 1949 it became the official organ of the
      Deutsche Gesellschaft fur Kinderheilkunde (German Society of Pediatrics),
      endorsed by the impressum since 1956. In 1993 the subscription of the journal
      became part of the membership fee of the Deutsche Gesellschaft fur
      Kinderheilkunde.

PMID- 8264678
TI  - [Acute mesenteric vein thrombosis. A rare complication after splenectomy due to
      autoimmune hemolytic anemia in childhood].
AB  - Mesenteric vein thrombosis is a rare but severe complication in children
      requiring splenectomy. We report on a 5-year-old boy with an autoimmune hemolytic
      anemia who underwent splenectomy because of severe side effects from cortisone
      therapy. 10 months after splenectomy he presented with signs of a paralytic
      ileus. Laparotomy showed mesenteric vein thrombosis with hemorrhagic bowel
      infarction requiring resection of two thirds of the small intestine. An early
      recognition and thrombolytic or surgical treatment of mesenteric vein thrombosis
      may reduce the incidence of hemorrhagic infarction, peritonitis, and secondary
      complications in these patients.

PMID- 8264679
TI  - [Monosymptomatic familial Mediterranean fever as the cause of fever of unknown
      origin].
AB  - A previously healthy 2 year old female child developed fever of unknown origin
      recurring in monthly cycles. The periodic fever attacks, family history and
      ethnologic criteria were in agreement with familial mediterranean fever, although
      further more major symptoms were missing. It was highly unusual to find
      repeatedly raised levels of angiotensin I converting enzyme, a finding previously
      not described in literature. Excluding any other differential diagnosis by
      intensive investigations, together with a positive metaraminol provocation test,
      the diagnosis of a rare, monosymptomatic variant of familial mediterranean fever
      was proposed. Amyloidosis was excluded by rectal biopsy. Monosymptomatic familial
      mediterranean fever is very seldom. We suggest to measure routinely angiotensin I
      converting enzyme for further evaluation of our findings.

PMID- 8264680
TI  - [Partial tracheal rupture in a newborn infant. A rare traumatic birth
      complication or intubation sequela?].
AB  - The neonate was born with the help of vacuum extraction because of difficult
      delivery of the shoulders. After birth respiratory distress developed and
      endotracheal intubation and artificial ventilation became necessary. When the
      tube was changed in the intensive care unit the infant's clinical status suddenly
      deteriorated. A rupture of the trachea was diagnosed immediately followed by
      surgery. The child survived without neurological sequelae. The chronological
      sequence of symptoms after birth suggests that the rupture of the trachea
      primarily developed during delivery and was secondarily enlarged by repeated
      endotracheal intubation.

PMID- 8264681
TI  - [In spinal symptoms remember toxoplasmosis].
AB  - A 4 weeks old girl presented a macrocephalus, elevated intracranial pressure and
      paralysis of both legs. The CT scan showed a hydrocephalus internus with stenosis
      of the aqueduct and periventricular calcifications. The cranial and spinal MRT
      scan revealed numerous lesions of the cerebral parenchyma and the spinal cord,
      which were detected after injection of Gadolinium Dimethylentriaminaceticacid (Gd
      DTPA). The serological examination confirmed the diagnosis of congenital
      toxoplasmosis.

PMID- 8264682
TI  - [Comments on the contribution by D. Kotzot et al. Townes-Brocks syndrome].

PMID- 8264683
TI  - [Congenital cystic bile duct dilatation. Presentation of clinical symptoms,
      diagnostic possibilities and therapy based on 6 cases].
AB  - BACKGROUND AND METHODS: Congenital cystic dilatation of the bile ducts represents
      an uncommon anomaly of the biliary system. We report on 6 patients suffering from
      cystic biliary duct dilatations which were treated in our hospital between 1980
      and 1992. Clinical signs included upper abdominal pain, white or clay-colored
      stool, icterus and/or palpable tumor. According to the classification of Todani,
      4 children had type Ia cysts, 1 child a type Va cyst and 1 child a type Ia cyst
      with extrahepatic biliary atresia. RESULTS: Among the diagnostic methods
      sonography is preeminent and permitted demonstration of intra- and extrahepatic
      biliary duct dilatations in all of our patients. In 2 patients small cystic
      dilatations could be distinguished from hepatic vessels by colour-coded Doppler
      sonography. CONCLUSION: The treatment of choice is the resection of the dilated
      extrahepatic biliary ducts followed by hepaticojejunostomy using the Roux-en-Y
      technique.

PMID- 8264684
TI  - [Obstructive apnea and periodic respiration in premature infants].
AB  - BACKGROUND: Disturbances of cardiorespiratory function are common clinical
      problems in preterm infants. Polygraphic recordings during sleep were performed
      in order to determine frequency and severity of idiopathic apnea of prematurity.
      METHOD: In 137 preterm infants at the corrected age of < +/- 0 weeks, 0-12 weeks,
      13-24 weeks and > or = 25 weeks respectively central and obstructive apnea and
      periodic breathing were recorded by polysomnography including nasal airflow and
      thoracic and abdominal breathing movements and compared with 50 normal full-term
      infants. RESULTS: Apnea frequency was inversely correlated to gestational age in
      premature and term infants. Whereas no differences were found concerning central
      apnea and periodic breathing, obstructive apnea occurred more frequently in
      premature than in term infants during the first weeks of life. CONCLUSIONS:
      Conclusively, in early infancy premature infants have an inclination to upper
      airway obstruction.

PMID- 8264685
TI  - [Computerized prescription service for pediatric intensive care].
AB  - Intensive care medicine relies on the fast and flawless organization of data. In
      addition, control of therapy requires many calculations. The computer program
      presented here improves and facilitates documentation of medical prescriptions on
      the ICU. The program can be run on affordable personal computers. Fluid balances
      can be managed easily while the program calculates the intake of calories,
      carbohydrates, protein, fat and electrolytes in the background. On entry of
      medications suggestions for the pediatric dosage are given automatically. Use of
      this program provides a flexible way of reusing and editing prescriptions, thus
      adding up to a time-gaining and precise way of writing intensive care
      prescriptions.

PMID- 8264686
TI  - [Early detection of amblyopia].

PMID- 8264687
TI  - The clinical and diagnostic role of anti-GM1 antibody testing.
AB  - There is increasing evidence that multifocal motor neuropathy (MMN) and some
      lower motor neuron (LMN) syndromes are immune-mediated and treatable. The
      frequent occurrence of high titers of anti-GM1 antibodies in these motor
      neuropathies raised hopes that serum testing would provide useful diagnostic
      information. Unfortunately, in routine practice, simple quantification of IgM
      binding to GM1 ganglioside has proved to be a test with poor sensitivity and
      specificity. We have found that much greater sensitivity and specificity for MMN
      and LMN syndromes can be obtained by determining serum antibody binding to panels
      of antigens, such as GM1, histone H3, and NP-9. These results suggest that
      combined measurement of serum antibody binding to GM1 and other antigens can
      provide tests that are useful in the diagnosis and management of motor neuropathy
      syndromes.

PMID- 8264688
TI  - Do GM1 antibodies induce demyelination?
AB  - We review clinical, neurophysiological, immunological, and experimental data
      concerning multifocal motor neuropathy (MMN), a newly recognized disorder that
      mimics MND. It is separated from MND by the presence of multifocal conduction
      block (CB) demonstrated electrophysiologically, and in some instances by the
      association of high titers of GM1 antibodies. The possible immunopathogenetic
      effect of GM1 antibodies is discussed. However, 70% of patients with MMNCB do not
      have elevated titers of GM1 antibodies, but may respond nevertheless to
      immunosuppressive treatment. Thus, so far unrecognized antibodies may react
      against some other epitopes in the paranodal region than those attacked by GM1
      antibodies to cause CB.

PMID- 8264689
TI  - Anti-GM1 antibodies and impaired blood-nerve barrier may interfere with
      remyelination in multifocal motor neuropathy.
AB  - Multifocal motor neuropathy has pure motor manifestation and nonremittent
      clinical courses. Antiganglioside antibodies, though variable in titers, are
      characteristically elevated in the majority of these patient. In our cases,
      pathological findings at the site of conduction block suggested impaired
      remyelination and disruption of blood-nerve barrier. These findings lead us to
      postulate that antibodies toward gangliosides or toward unknown antigens
      containing gangliosides initiate motor-specific demyelination. The lesion, once
      produced, may persist as a result of impaired remyelination caused by disrupted
      blood-nerve barrier. The antibodies bound to denuded axons may also interfere
      with a remyelinative process. If so, antibodies may not always be circulating,
      thus accounting for variable levels of titers.

PMID- 8264690
TI  - Distal sensory fiber involvement in inflammatory demyelinating polyneuropathies.

PMID- 8264691
TI  - Handcuff neuropathy involving the dorsal ulnar cutaneous nerve.

PMID- 8264692
TI  - Transcranial cortical stimulation in syringomyelia.

PMID- 8264693
TI  - Depressor septi nasi myokymia.

PMID- 8264694
TI  - Magnetic evoked potentials (MEPs) are larger in left-handed subjects.

PMID- 8264695
TI  - Bell's palsy: an eponym that often leads to confusion.

PMID- 8264696
TI  - Modulation of the tibialis anterior and triceps surae (soleus) H-reflexes during
      gait.

PMID- 8264697
TI  - The breathing arm.

PMID- 8264698
TI  - AAEM minimonograph #41: neuromuscular diseases associated with HIV-1 infection.
AB  - Neuromuscular diseases occur in as many as 50% of patients infected with human
      immunodeficiency virus type 1 (HIV-1). All forms of neuromuscular disease have
      been reported, including axonal neuropathy, demyelinating neuropathy,
      mononeuropathy multiplex, polyradiculitis, ALS-like syndromes, disorders of
      neuromuscular transmission, myopathy, and toxic neuropathies due to medication
      side effects. Neuromuscular disease is often the presenting manifestation of HIV
      1 infection. Infection with cytomegalovirus (CMV) is associated with different
      types of neuropathy including mononeuritis multiplex and polyradiculopathy. There
      is effective treatment for many of the associated disorders including chronic
      inflammatory demyelinating neuropathy, CMV-mediated neuropathies, and myopathy.
      Treatment of CMV-mediated mononeuropathy multiplex may be life saving. The
      different neuromuscular syndromes associated with different stages of HIV-1
      infection may be due, in part, to different levels of immunocompetence.

PMID- 8264699
TI  - Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of
      muscular dystrophies.
AB  - Dystrophin, the protein product of the Duchenne muscular dystrophy (DMD) gene, is
      associated with a large oligomeric complex of sarcolemmal glycoproteins,
      including dystroglycan which provides a linkage to the extracellular matrix
      component, laminin. In patients with DMD, the absence of dystrophin leads to the
      loss in all of the dystrophin-associated proteins, causing the disruption of the
      linkage between the subsarcolemmal cytoskeleton and the extracellular matrix.
      This may render the sarcolemma vulnerable to physical stress. These recent
      developments in the research concerning the function of the dystrophin
      glycoprotein complex pave a way for the better understanding of the pathogenesis
      of muscular dystrophies.

PMID- 8264700
TI  - Immunohistochemical characterization of human masseter muscle spindles.
AB  - An enzyme- and immunohistochemical study has been performed on human masseter
      muscle spindles. Antibodies selective for different myosin heavy chain (MHC)
      isoforms and M-band proteins (M-protein, myomesin, and MM-CK) were used. The
      expression of these proteins was determined in the different intrafusal fiber
      types. Nuclear bag1 and nuclear bag2 fibers expressed predominantly slow-twitch
      and slow-tonic MHCs. The bag2 fibers in addition contained fetal MHC. Nuclear
      chain fibers coexpressed embryonic, fetal, and fast-twitch MHCs. The bag2 and
      chain fibers contained all three M-band proteins, whereas the bag1 fibers
      contained only myomesin. In general the MHC expression in the human masseter
      intrafusal fiber types was similar to that previously reported for limb muscles
      in man as well as for limb and masseter muscles in other species. However, the
      number of intrafusal fibers per spindle was unusually high (up to 36). This
      reinforces the idea that masseter muscle spindles have a strong proprioceptive
      impact during the control of jaw movements.

PMID- 8264701
TI  - Idiopathic generalized myokymia.
AB  - Idiopathic generalized myokymia (IGM) is a rare, heterogeneous, and poorly
      understood syndrome. We present analysis of 75 reported cases in the world
      literature. IGM affects men and women equally, with a mean age of onset 29 +/- 19
      years. Patients' common presenting complaints are stiffness (60%), cramps (12%),
      weakness (12%), and muscle twitching (4%). Family history is positive in 30%. In
      addition to generalized clinical myokymia (92%), abnormal neurologic findings
      include: hyporeflexia (70%), weakness (45%), grip myotonia (39%), and calf
      hypertrophy (16%). Electrical activity consisting of spontaneous continuous motor
      unit activity and/or electrical myokymia was documented in all patients. When
      electrical myokymia was observed (66%), the grouped discharges where irregular
      and had an interburst frequency of 2-300 Hz. Both phenytoin and carbamazepine are
      effective treatments. We conclude that IGM has a wide spectrum of symptoms and
      severity and should be considered in all patients that present with stiffness,
      cramps, or muscle twitching. EMG greatly aids in diagnosis.

PMID- 8264702
TI  - Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese
      family with mitochondrial DNA point mutation in tRNA(Lys) gene.
AB  - We report myoclonic epilepsy with ragged-red fibers (MERRF) syndrome in a Chinese
      family with confirmed mitochondrial DNA point mutation. Six members of the family
      including the grandmother, two siblings, and three grandchildren were affected.
      Among them, action myoclonus was seen in five; short stature, muscle weakness,
      and mental retardation in four; lactic acidosis, hearing impairment, and ataxia
      in two; and seizures in one. Muscle biopsy from two affected siblings revealed
      ragged-red fibers and abundant subsarcolemmal mitochondria with paracrystalline
      inclusions. Pedigree analysis suggests a maternal transmission. Analysis of
      mitochondrial DNA showed a point mutation from A to G at the 8344th nucleotide
      position located in the tRNA(Lys) gene. To our knowledge, this is the first
      report of MERRF syndrome with such genetic defect from a Chinese family. The
      present and previous reports support the notion that mitochondrial DNA point
      mutation at the 8344th nucleotide position is the most common cause of MERRF
      syndrome.

PMID- 8264703
TI  - Early appearance of aging phenomenon in the interdigital nerves of the foot.
AB  - To test the hypothesis that the interdigital nerves of the foot are the first to
      be affected by aging, we studied sensory nerve conduction in the nerves of normal
      subjects between the ages of 10 and 79, using the near-nerve needle technique. In
      normal individuals up to the seventh decade we could get sensory CNAPs without
      any difficulty by 256 averagings. In 10% of the 70-79-year-old group we could not
      obtain those potentials in some digital or interdigital nerves. Between the 10-49
      year-old and 50-79-year-old groups, there was a significant slowing in the
      sensory NCVs, a significant decline in the amplitude of the sensory CNAPs, and a
      significant prolongation of the duration of sensory CNAPs for the various
      interdigital nerves. Thus, our study documented the earlier presence of aging
      phenomenon in the sensory nerve conduction of the interdigital nerves of the foot
      compared with the previously reported sensory nerve conduction change with age in
      the other nerves. We conclude that the "degeneration" of various interdigital
      nerves of the foot is accelerated from the early 50s on, possibly resulting from
      the normal aging process.

PMID- 8264704
TI  - The effects of hyperthyroidism on muscular dystrophy in the mdx mouse: greater
      dystrophy in cardiac and soleus muscle.
AB  - Muscle damage and repair were studied in mdx mice treated with triiodothyronine
      (T3) for 14 days. Hindlimb and cardiac muscles were examined for the severity of
      dystrophy, the degree of muscle centronucleation, and fiber size. In control and
      mdx mice, cardiac hypertrophy and skeletal muscle atrophy were present after T3
      treatment. Both cardiac and soleus (but not fast-twitch) muscles had larger, more
      frequent dystrophic lesions in T3-treated mdx mice, and mdx soleus had an
      increased area of new myotubes after T3. Skeletal myogenesis in mdx mice may have
      been delayed by excess T3, possibly related to the general reduction in staining
      for basic fibroblast growth factor in hyperthyroid mice. These are the first
      observations of a metabolic perturbation which worsens mdx dystrophy and possibly
      repair in a muscle-specific manner, and are likely related to T3-induced changes
      in myosin heavy chain expression, and to increased mechanical strain on
      dystrophin-deficient muscles.

PMID- 8264705
TI  - Long lasting excitability changes in human peripheral nerve.
AB  - When pairs of equal but submaximal electrical stimuli are delivered to a
      peripheral nerve, the second stimulus does not always excite the same number of
      fibers as the first. The number of fibers responding to the second stimulus
      depends on the interstimulus interval; the refractory period, a well-defined
      period of hypoexcitability, is followed by longer lasting and less well
      characterized periods of hyper- and hypoexcitability. These cycles last at least
      200 ms after the initial stimulus. We have carefully studied these cycles of
      excitability in human peripheral nerve in 12 normal subjects. The magnitude of
      excitability changes were found to be much greater in motor fibers than in mixed
      nerve; under some conditions, the motor response was reduced by more than 80% at
      interstimulus intervals of 40 ms, while the mixed nerve response never varied by
      more than 20%. In addition, the amplitude of the excitability changes varied as a
      function of the stimulus strength, so that stimuli that were near threshold or
      evoked near maximal responses were associated with smaller excitability changes
      than stimuli evoking midrange responses. Given that the excitability fluctuations
      are of large magnitude and occur at interresponse intervals easily achieved
      during physiological firing, it is suggested that they may be important modifiers
      of firing rate under experimental or physiological conditions.

PMID- 8264706
TI  - Inability of insulin to maintain normal nerve function during high-frequency
      stimulation in diabetic rat tail nerves.
AB  - The effect of insulin on the response to long-term high-frequency stimulation
      (HFS = 143 Hz for 20 min) was studied in mixed tail nerves of acute
      streptozotocin-induced diabetic rats. In consecutive tests, untreated diabetic
      rats showed a significant decrease in nerve conduction velocity (NCV) and peak-to
      peak amplitude (P-Pamp) and the depression of the P-Pamp during HFS was
      augmented. In contrast, NCV and P-Pamp in the insulin-treated rats were unchanged
      from the prediabetic state, but the depression of the P-Pamp during HFS reached
      the same degree as in untreated rats. This implies that although insulin
      treatment of acute experimental diabetes is able to preserve a normal NCV and P
      Pamp in the resting state, it is unable to preserve normal nerve function under
      stress produced by HFS. Monitoring of the axon membrane functional capacity may
      have clinical implications in the control of peripheral neuropathies.

PMID- 8264707
TI  - Hereditary motor and sensory neuropathy type I: clinical and neurographical
      features of the 17p duplication subtype.
AB  - Forty-four affected individuals, aged 8-68 years (mean 34 years), from six
      families with hereditary motor and sensory neuropathy type I (HMSN I, Charcot
      Marie-Tooth disease type 1) were investigated to determine the clinical and
      electroneurographical characteristics of the HMSN I subtype that is defined by
      the presence of a DNA duplication on chromosome 17p. Motor nerve conduction
      velocity (MNCV) and, to a lesser extent, compound muscle action potential
      amplitude, were inversely related to clinical severity. Neither clinical severity
      nor MNCV were significantly related to age. These results suggest that the
      primary pathological process is not, or only slightly active after childhood.

PMID- 8264708
TI  - Paraneoplastic pseudo-obstruction, mononeuropathy multiplex, and sensory
      neuronopathy.
AB  - A patient with mononeuropathy multiplex, sensory neuronopathy, and diffuse
      intestinal pseudo-obstruction consisting of gastroparesis and impaired small and
      large bowel motility was found to have a small cell carcinoma of the lung. The
      constellation of findings were indicative of paraneoplastic neuropathy, which was
      confirmed with the appropriate antibody studies demonstrating antineuronal
      nuclear antibodies. Identification of paraneoplastic neuropathy is important,
      since early treatment of the primary cancer, which is virtually always a small
      cell carcinoma of the lung, may halt the progression of the disorder.

PMID- 8264709
TI  - Antiganglioside antibodies do not necessarily play a role in multifocal motor
      neuropathy.
AB  - Multifocal motor neuropathy (MMN) is a disorder with a highly characteristic
      clinical picture and one which is defined by a specific electrodiagnostic
      abnormality, namely, multifocal conduction block which is confined to motor
      axons. Sensory axons which traverse segments of severe or even complete motor
      conduction block conduct normally. A proportion of patients with MMN also have
      elevated levels of antibodies to GM1 ganglioside. However, about one half of MMN
      patients lack elevated levels of these antibodies and many others have only
      modest elevations, to a degree often seen in other neurological and even non
      neurological disorders. Furthermore, clinical and electrophysiological
      improvement of MMN in response to treatment with high dose intravenous
      immunoglobulin is achieved in the absence of any change in antiglycolipid levels.
      Injection of serum from patients with MMN and elevated GM1 antibody levels
      produces demyelination in recipient rat nerves, suggesting a pathogenetic role
      for these antibodies in demyelination. However, sera of patients with identical
      antibody titers in other motor system diseases produced no demyelination,
      suggesting that the demyelinating factor resides in some other serum fraction. At
      present, there is insufficient evidence to support the contention that these
      antibodies play a critical pathogenetic role in MMN. Until more evidence is
      available it is important to define MMN on the basis of a characteristic clinical
      picture and a unique electrodiagnostic abnormality rather than on a pattern of
      serum antibodies.

PMID- 8264710
TI  - Clinical and mycological spectra of Wangiella dermatitidis infections.
AB  - The article reviews 37 cases of phaeohyphomycosis from the world literature up to
      1992 accepted as being caused by Wangiella dermatitidis. The various clinical
      aspects of these infections are characterized, and the nomenclatural implications
      in the history of this emerging pathogen are discussed.

PMID- 8264711
TI  - Calcium regulates in vitro dimorphism in chromoblastomycotic fungi.
AB  - Cladosporium carrionii, Fonsecaea pedrosoi and Phialophora verrucosa, the three
      most important agents of chromoblastomycosis, produced large numbers of sclerotic
      bodies at 25 degrees C, and greater numbers at 37 degrees C, after inoculation
      into a defined pH 2.5 medium containing 0.1 mmol l-1 Ca2+. Higher concentrations
      of Ca2+ reversed this tendency and promoted maintenance of hyphal growth.
      Addition of the Ca2+ chelator EGTA to the same medium buffered at pH 6.5 also
      induced sclerotic bodies, but in a more concentration-dependent fashion. EGTA at
      0.5-1.0 mmol l-1 induced maximum numbers of sclerotic bodies in Cl. carrionii,
      whereas 2 and 8 mmol l-1 concentrations were required for the same results with
      F. pedrosoi and P. verrucosa, respectively. These findings suggest that Ca2+
      concentrations in human tissue may play a paramount role in the dimorphic
      switching between hyphae and sclerotic bodies among chromoblastomycotic agents
      during infection.

PMID- 8264712
TI  - Cryptococcosis in domestic mammals.
AB  - After a brief review of cryptococcosis in dogs and cats from the literature from
      1980 to 92, three cases in dogs (two epidemiologically strictly connected) and
      two in cats are reported. In the three dogs and in one of the two cats lesions
      were seen in many sites, but only one dog and one cat had a central nervous
      system localization. The cutis was affected in the three dogs and in one cat; in
      two of the dogs it was probably the primary lesion, and in the cat it was the
      only lesion. An unidentified genetic defect was probably the predisposing factor
      in two of the dogs of the same litter, exposed to soil cryptococcal contamination
      (from pigeon guano); a third dog, of different breeding, was not infected.
      Steroid treatment was predisposing in one cat. Flucytosine treatment was
      initially successful in two dogs, but in both relapses were reported; in one dog
      fluconazole treatment was successful. The isolates, before and after treatment,
      demonstrated a large increase in flucytosine MIC, strictly connected with the
      relapse.

PMID- 8264713
TI  - Identification of clinical strains of Candida albicans by DNA fingerprinting with
      the polymerase chain reaction.
AB  - DNA polymorphisms generated by the polymerase chain reaction (PCR) were used to
      differentiate clinical isolates of Candida. This PCR method employed single
      primers that were originally designed as hybridization probes for DNA
      fingerprinting experiments to probe minisatellite and microsatellite DNA
      sequences. To evaluate this procedure, 35 isolates from 20 patients in several
      intensive care units and 12 isolates obtained from the oral cavities of healthy
      dental patients were fingerprinted. The PCR-fingerprint patterns of isolates of
      Candida albicans from the immunocompromised patients revealed fewer differences
      than isolates from the dental service. Multiple isolates from different body
      sites of the same patients revealed that patients may harbour isolates of Candida
      with the same or different PCR-fingerprints. Since this method is generally
      simpler and faster than established methods of biotyping medically important
      yeasts, PCR-fingerprinting may prove useful for the surveying of large numbers of
      pathogens for epidemiological studies.

PMID- 8264714
TI  - Cutaneous sporotrichosis in the period 1978-1992 in the province of Bari, Apulia,
      Southern Italy.
AB  - The authors report 16 cases of cutaneous sporotrichosis observed in the province
      of Bari, southern Italy, since 1978. While no more than 55 cases have been
      documented in other European countries in the last 30 years, in Italy 58 cases
      (present series included) have been recorded in the same time period.
      Furthermore, 42 of them (73.7%) originated from Apulia. This unexpectedly high
      incidence rate in Italy, and in Apulia in particular, provides evidence of the
      important role played by this area in the ecoepidemiology of sporotrichosis in
      Europe.

PMID- 8264715
TI  - Liposomal amphotericin B (AmBisome) treatment of invasive fungal infections in
      immunocompromised children.
AB  - Thirteen children were treated for 16 cases of proven (8 cases) or suspected (8
      cases) invasive fungal infections caused by Candida spp. (9 cases), Aspergillus
      spp. (3 cases) and mycetoma (1 case). The type of fungal infection was not
      identified in 3 cases. Liposomal amphotericin B (AmBisome) was instituted because
      of the failure of previous treatments in 9 cases, toxicity-associated
      amphotericin B therapy in 4 cases and renal insufficiency in 3 cases. AmBisome
      was given for a median of 19 days (range 3-55) with a mean cumulative dose of 1.8
      +/- 1.3 g (+/- SD). Acute toxic side-effects were not seen in any patients.
      Slight increases in serum creatinine were seen in 3 cases during AmBisome
      therapy. No other side-effects were observed. Among 8 cases with proven invasive
      fungal infection, 6 were clinically cured, one had persistent fungi and one died
      after only 3 days of AmBisome therapy. Eradication of fungi was documented in 5
      out of 6 cases. Among the 8 cases with presumed fungal infections, 6 were
      clinically cured, one improved and one died after 6 days of treatment. To
      conclude, AmBisome can safely be given to children with invasive fungal
      infections; side-effects are minimal and among those treated for at least a week,
      the overall cure rate was 86% (12 out of 14).

PMID- 8264716
TI  - Fluconazole in the management of endophthalmitis in disseminated candidosis of
      heroin addicts.
AB  - Seven heroin addicts were treated with fluconazole for endophthalmitis. All the
      patients had cutaneous lesions: deep-seated scalp nodules and/or pustulosis in
      hairy zones. One patient had an abscess at the venipuncture site. Candida
      albicans was isolated from all the extraocular sites in all the patients. Five
      patients were treated with 400 mg of intravenous fluconazole on the first day,
      followed by 200 mg (i.v.) for one week and finally 200 mg daily orally for a
      further two weeks. Two patients were treated exclusively with oral fluconazole
      (400 mg on the first day, followed by 200 mg daily for three consecutive weeks).
      Tolerance to fluconazole was good and it was not necessary to stop treatment for
      any patient. All the cutaneous lesions stabilized and healed. The eye lesions
      cleared completely in all cases, except in one patient in whom vitrectomy was
      indicated, and in whom there was a poor response to the exclusive treatment with
      fluconazole and associated corticosteroids.

PMID- 8264717
TI  - Thermomucor indicae-seudaticae on human skin.
AB  - Thermomucor indicae-seudaticae Subrahmanyam et al. was found for the first time
      growing as commensal associated with pityriasis versicolor on the skin of a 25
      year-old man living in a small village near Pune, Maharastra, India. The clinical
      observations and morphological characters are presented. A small percentage of
      zygospores was found to germinate in situ but further stages of development could
      not be found.

PMID- 8264718
TI  - Immunohistological characterization of the cellular infiltrate in
      dermatophytosis.
AB  - The local cell composition of skin infections caused by Trichophyton rubrum (13
      cases) and Microsporum canis (2 cases) was examined using monoclonal antibodies
      and the ABC immunoperoxidase technique. The number of Langerhans cells increased
      both in the epithelium and in the dermis of the mycotic area. Apart from these,
      only T cells were found in the dermis, among which helper cells were predominant.
      The helper/suppressor ratio showed variations depending upon the pathogen.

PMID- 8264719
TI  - In vitro comparison of antifungal effects of a coal tar gel and a ketoconazole
      gel on Malassezia furfur.
AB  - Malassezia furfur seems to be a major pathogenetic factor in seborrhoeic
      dermatitis, a frequent human skin disease. To estimate the antifungal properties
      of a coal tar gel (5 mg ml-1 coal tar) which is used in the treatment of
      seborrhoeic dermatitis of the scalp, we compared its effects on the in vitro
      growth of M. furfur with those of a ketoconazole gel (20 mg ml-1 ketoconazole).
      None of the gels was fungicidal within incubation times up to 20 min. During a
      single application, both gels remain on the skin for only 5 min. Fungicidal
      effects are consequently unlikely to play a substantial therapeutic role.
      Fungistatic effects were observed with both gels. In cultures inoculated with 1 x
      10(3) cells ml-1, a 1:49 152 dilution of the ketoconazole gel and a 1:768
      dilution of the coal tar gel still showed inhibitory effects. At inoculum
      densities of 1 x 10(5) ml-1, both gels were fungistatic only in dilutions of a
      maximum of 1:40. Our results suggest that under clinical treatment conditions the
      fungistatic activities of both preparations should be comparable.

PMID- 8264720
TI  - Fungitoxicity of essential oils against dermatophytes.
AB  - Sixteen essential oils were screened in vitro for their fungitoxicity against the
      two dermatophytes Trichophyton rubrum and Microsporum gypseum. Five oils (from
      Artemisia nelagrica, Caesulia axillaris, Chenopodium ambrosioides, Cymbopogon
      citratus and Mentha arvensis) showed strong activity and were assessed for their
      fungitoxicity against eight other dermatophytes as well as against Aspergillus
      fumigatus and Cladosporium trichoides. These five essential oils by formulation
      of ointments were able to cure experimental ringworm in guinea pigs within 7 to
      12 days. Artemisia oil was found to be the most effective essential oil.

PMID- 8264721
TI  - Characterisation of a glutamine- and proline-rich protein (QP protein) from
      Theileria parva.
AB  - We have isolated a clone from a Theileria parva infected lymphocyte cDNA library
      which has the potential to encode a protein of 480 amino acids. This protein is
      particularly rich in glutamine and proline and has some short repeated amino acid
      motifs based on the sequences QPXP and QPXQ. We have called it the 'QP protein'.
      Southern blotting suggests that the QP protein gene is present as a single copy
      in the T. parva Muguga genome. Northern blotting revealed that the gene is
      transcribed in both schizonts and piroplasms. We have expressed part of the QP
      protein as a fusion with glutathione S-transferase in Escherichia coli and used
      this product to raise an anti-QP protein serum. Western blots of T. parva lysates
      using this serum showed a major polypeptide of approximately 100 kDa and two
      further polypeptides of approximately 67 and 72 kDa. Indirect immunofluorescence
      assays using the anti-QP protein serum on infected cells showed that the protein
      is associated with the schizont. The pattern of staining in the indirect
      immunofluorescence assays and the structure of the protein suggest that it is a
      component of the schizont membrane.

PMID- 8264722
TI  - Cloning and characterization of a surface antigen of Eimeria tenella merozoites
      and expression using a recombinant vaccinia virus.
AB  - A rabbit serum raised against Eimeria tenella merozoites was used to screen a
      lambda gt11 cDNA library made from merozoite mRNA of E. tenella. The insert of
      the phage clone lambda Mz 5-7 revealed an open reading frame consisting of 945
      nucleotides, encoding a 33-kDa protein. This size is consistent with the size of
      a protein translated in vitro from merozoite mRNA and immunoprecipitated with
      monospecific anti-Mzp 5-7 antibodies. A smaller protein of 24 kDa, located on the
      surface of the parasite, also reacted with the monospecific antiserum and is the
      potential processed form of the Mzp 5-7. Furthermore, a recombinant vaccinia
      virus expressing the Mzp 5-7 antigen was constructed and used to immunize
      chickens.

PMID- 8264723
TI  - The S-antigen of Plasmodium falciparum: repertoire and origin of diversity.
AB  - S-antigens are heat-stable, highly polymorphic proteins released by Plasmodium
      falciparum at the time of schizont rupture. Previously determined S-antigen
      sequences allowed the proposal of a general gene structure consisting of 5
      sequence blocks. The sequence of the central block of tandem repeats provides a
      useful means of distinguishing the S-antigen allele and also its serotype,
      whereas the amino and carboxy terminal sequences defined the S-antigen family, 4
      of which have been described. We present the sequence of 3 new S-antigen alleles,
      for the isolates HB3, KF1916 and KF1917. The allele-defining repeat sequence is
      ETGPGKAGEQG for HB3, GDQTEGS(S/A)GGK for KF1917 and AGSNE(E/K) for KF1916. The
      sequences of these newly described S-antigens are consistent with the proposed
      general gene structure and all belong to defined families, although carboxy
      terminal sequences appear to be much more variable within a family than
      previously realised.

PMID- 8264724
TI  - Regulation of L-proline transport in Leishmania donovani by extracellular pH.
AB  - We have previously shown that Leishmania donovani promastigotes adapted to long
      term culture at acidic pH can serve as a model to study parasite development in a
      lysosomal-like environment. In this study we investigated the effect of growth pH
      on L. donovani L-proline transport systems. Reducing the pH of the growth medium
      causes an up to 7-fold decrease in the extent of L-proline transport. Transport
      resumes after switching the culture from pH 4.5 to pH 7 for 48 h by a protein
      synthesis-dependent process. The pH optimum for transport changes from 7.5 in
      promastigotes grown at pH 7 to 5.5 in cells grown at pH 4.5. In addition, kinetic
      analysis of L-proline transport showed that Vmax in pH 4.5-grown L. donovani
      promastigotes is one-tenth that of cells grown at pH 7 (4.5 and 44.7 nmol min-1
      (10(8) cells)-1, respectively). The apparent Km for L-proline in pH 4.5
      promastigotes is one-half of the Km in pH 7 cells (0.30 and 0.65 mM,
      respectively). In contrast to L-proline transport, D-glucose transport
      demonstrates a growth pH-independent activity: Km and Vmax as well as optimum pH
      of transport are similar in promastigotes grown at either pH 7 or pH 4.5. Taken
      together, the results indicate that in L. donovani, expression and activity of L
      proline transport is regulated by culture pH. The pH-dependent expression of L
      proline transporters may be of physiological significance during the promastigote
      amastigote transition.

PMID- 8264725
TI  - Reversion to virulence in Leishmania major correlates with expression of surface
      lipophosphoglycan.
AB  - An attenuated clone of Leishmania major was produced by chemical mutagenesis with
      N-methyl-N'-nitro-N-nitrosoguanidine and was biochemically characterized to
      determine the reason(s) for its loss of virulence. We found that the degree of
      virulence of L. major did not correlate with either the level of expression of
      promastigote surface protease (PSP) or with the enzymatic activity of the
      molecule. In contrast, the levels of lipophosphoglycan (LPG) expressed by the
      attenuated clone were found to be at least 6-fold less than those of virulent L.
      major. When the attenuated L. major was injected into BALB/c mice and allowed to
      revert to virulence, the degree of reversion to virulence that the parasites
      underwent correlated directly with the amount and form (metacyclic) of LPG
      expressed by the parasites. Thus, these results further implicate LPG as an
      important Leishmania virulence factor.

PMID- 8264726
TI  - Purification of a 74-kilodalton surface glycoprotein from heart myoblasts that
      inhibits binding and entry of Trypanosoma cruzi into heart cells.
AB  - We have identified and purified a 74 kDa surface glycoprotein from heart
      myoblasts that specifically binds to Trypanosoma cruzi trypomastigotes, and
      inhibits the attachment and internalization of trypomastigotes into these cells.
      The native form of the 74 kDa glycoprotein was purified to apparent homogeneity
      by preparative scale isoelectrofocusing and anion exchange chromatography. Pre
      incubation of trypomastigotes with soluble 74 kDa glycoprotein strongly inhibited
      the binding and internalization of trypomastigotes into heart myoblast monolayers
      in a concentration dependent-manner. Pre-incubation of heart myoblast monolayers
      with antibodies specific to the purified 74 kDa glycoprotein also strongly
      inhibited trypomastigote binding and internalization into heart cells in a
      concentration dependent manner. These results support the notion that the surface
      74 kDa glycoprotein is a target molecule on heart myoblast cells to which T.
      cruzi binds in order to invade them.

PMID- 8264727
TI  - Origin of reactive oxygen species in erythrocytes infected with Plasmodium
      falciparum.
AB  - Oxidative radicals are demonstrably produced in malaria-infected erythrocytes. In
      order to verify the biochemical origin of these radicals, erythrocyte lysate was
      brought to acid pH to mimic the environment of the parasite food vacuole into
      which host cell cytosol is transferred during parasite feeding. Oxyhemoglobin,
      but not deoxyhemoglobin, is rapidly converted to methemoglobin at rates which
      decline with increasing pH. The rate of conversion is further increased in the
      presence of the catalase inhibitor 3-amino-1,2,4-triazole (3-AT) and the extent
      of inhibition of the lysate catalase increases upon acidification, implying that
      H2O2 is thus produced by the spontaneous dismutation of superoxide radicals
      generated during methemoglobin formation. Intact Plasmodium falciparum
      trophozoite-infected human red blood cells (TRBC) were shown to produce H2O2 and
      OH radicals about twice as much as normal erythrocytes, as evidenced by the
      inhibition of endogenous catalase activity in the presence of 3-AT and the
      degradation of deoxyribose, respectively. Increased H2O2 levels and catalase
      activity were found in both host cell and parasite compartments. No increase in
      H2O2 production over that observed in uninfected erythrocytes could be detected
      at the ring stage when host cell digestion is absent. H2O2 and OH radicals
      production in TRBC was considerably reduced when digestion of host cell cytosol
      was inhibited either by antiproteases (which reduce the proteolysis of imported
      catalase) or by its alkalinization with NH4Cl (which reduce methemoglobin
      formation). These results suggest that reactive oxygen species are produced in
      the parasite's food vacuole during the digestion of host cell cytosol, and are
      able to egress from the parasite to the host cell compartment.

PMID- 8264728
TI  - Purification and characterization of DNA polymerases from Plasmodium falciparum.
AB  - Fractionation of Plasmodium falciparum cellular extracts by fast protein liquid
      chromatography (FPLC) identified at least two different DNA polymerases. An
      aphidicolin-sensitive activity co-purified with a primase activity. This, in
      combination with other characteristics (processivity, sensitivity to other
      inhibitors), most likely classifies this enzyme as an alpha-like DNA polymerase.
      It was, however, relatively resistant to N2-(p-n-butylphenyl)deoxyguanosine 5'
      triphosphate (IC50 = 6.6 microM) and differs in this aspect from the host
      homologue, possibly indicating structural differences between host and parasite
      DNA polymerase alpha. The other DNA polymerase matched eukaryotic DNA polymerase
      gamma in all properties tested.

PMID- 8264729
TI  - Biochemical properties of cloned glutathione S-transferases from Schistosoma
      mansoni and Schistosoma japonicum.
AB  - cDNA clones encoding a 28-kDa subunit glutathione S-transferase (GST) from
      Schistosoma mansoni (Sm28GST) and a 26-kDa subunit GST from Schistosoma japonicum
      (Sj26GST) have been expressed in bacterial systems. The recombinant proteins were
      purified to homogeneity by batch-wash glutathione-agarose affinity chromatography
      and their biochemical properties investigated. Gel filtration chromatography
      indicated that both recombinant GSTs are homodimeric proteins. Resolution of
      Sm28GST and Sj26GST by chromatofocusing in the ranges pH 9-6 and pH 7-4 gave pI
      estimates of 7.4 and 5.0, respectively. Kinetic analyses suggested that both
      Sm28GST and Sj26GST operate via a sequential bisubstrate catalytic mechanism.
      Sm28GST and Sj26GST displayed a mosaic of mammalian Alpha-, Mu- and Pi-type
      substrate specificities and inhibitor sensitivities. However, multivariate
      analysis suggests that Sm28GST has an overall catalytic homology with mammalian
      Mu class GSTs, whilst the enzymatic properties of Sj26GST appear to constitute a
      hybridisation of Mu and Alpha class features. Both recombinant GSTs interact with
      a range of hydrophobic ligands including haematin and related compounds, bile
      acids and several anthelmintics. Sm28GST and Sj26GST possess relatively limited
      selenium-independent glutathione peroxidase activities, but are able to catalyse
      the glutathione conjugation of members of the trans,trans-alka-2,4-dienal, trans
      alk-2-enal and 4-hydroxyalk-2-enal series of reactive carbonyls (known secondary
      products of lipid peroxidation).

PMID- 8264730
TI  - Isolation, characterization and analysis of the expression of the Leishmania
      ribosomal PO protein genes.
AB  - Two tandemly linked genes are present in the Leishmania infantum genome that code
      for the acidic ribosomal PO protein. The genes are identical in the coding
      region, although a striking lack of nucleotide sequence conservation is observed
      when the boundaries of the coding regions between both genes are compared. The 3'
      untranslated regions of the two genes are, moreover, different in size. The
      deduced amino acid sequence of the L. infantum PO protein (LiPO) shows a high
      degree of sequence conservation, including the highly charged conserved C
      terminal domain, with the ribosomal PO proteins of other eukaryotic organisms.
      Northern blot experiments showed that two different size class transcripts are
      expressed in the gene cluster and that the steady state level of each of the
      transcripts in logarithmic phase promastigotes is markedly different. The
      abundance of both transcripts is down-regulated in parasite cultures on reaching
      stationary phase. Since it seems that the two Leishmania ribosomal PO genes are
      expressed in a single polycistronic transcript, it is likely that the different
      levels of PO mRNAs observed in cultured cells is due to a postranscriptional
      regulatory mechanism.

PMID- 8264731
TI  - Biosynthesis of isoprenoid compounds in Schistosoma mansoni.
AB  - The isoprenoid biosynthetic capacity of digenetic trematodes was investigated by
      following the fate of [14C]mevalonic acid incorporated by Schistosoma mansoni
      during maintenance in axenic culture. Isoprenoid compounds were analyzed by thin
      layer chromatography and high-performance liquid chromatography. Of the
      nonsaponifiable lipid classes, radioactivity was recovered in the dolichols,
      ubiquinones and in the short-chain isoprenoid alcohols. The latter group of
      lipids included geraniol, farnesol, geranylgeraniol and a compound tentatively
      identified as 2,3-dihydrogeranylgeraniol. Radioactivity derived from
      [14C]mevalonate was also incorporated into the saponifiable lipids, with 2,3
      dihydrogeranylgeranoic acid accompanied by much less geranylgeranoic acid being
      detected in the triacylglycerol-containing fraction. Similarly, geranylgeraniol
      and the dihydro derivative were also detected as esters, presumably with fatty
      acids. The possible significance of the results is discussed.

PMID- 8264732
TI  - A major surface antigen of procyclic stage Trypanosoma congolense.
AB  - Five monoclonal antibodies (mAb) were raised that bound to the surface of
      procyclic stage Trypanosoma congolense with high intensity in immunofluorescence.
      Immunoblot analysis of trypanosome lysates using 3 of these mAb revealed a
      diffuse SDS-PAGE band of 36-40 kDa. The purified antigen did not react with
      Coomassie Blue or silver stains, but did stain blue with Stains-all, indicating
      acidity. For the one mAb tested, the epitope was periodate-sensitive and
      therefore probably glycan. Although this antigen shares properties with
      procyclin/PARP, which forms a surface coat on procyclic Trypanosoma brucei, a
      search in T. congolense for homologues of a procyclin/PARP gene revealed only non
      coding sequence of partial similarity. Using a differential screen, a procyclic
      stage T. congolense cDNA clone was isolated that encoded a putative 256-amino
      acid protein containing 2 peptides chemically sequenced independently by Beecroft
      et al. [36]. The protein, termed glutamate and alanine-rich protein (GARP), has
      potential hydrophobic leader and tail sequences (the latter with potential for
      replacement by a glycosyl phosphoinositol anchor) and no potential N-linked
      glycosylation sites. It has no significant sequence homology with known proteins.
      Antibodies against a translational fusion of GARP bound specifically in Western
      blots to a band very similar to that detected by the mAb and also to the purified
      antigen. Immunogold electron microscopy revealed a dense packing of the antigen
      on the cell surface. It appears that procyclic T. brucei and T. congolense have
      major surface proteins with structural analogy, but with no sequence homology.

PMID- 8264734
TI  - High sensitivity of detection of human malaria parasites by the use of nested
      polymerase chain reaction.

PMID- 8264733
TI  - Characterization of a putative ornithine aminotransferase gene of Plasmodium
      falciparum.

PMID- 8264735
TI  - The gene for the TATA box-binding protein of Onchocerca volvulus.

PMID- 8264736
TI  - Sequence analysis of genes encoding the light subunit of the Entamoeba
      histolytica galactose-specific adhesin.

PMID- 8264737
TI  - Residential radon exposure and lung cancer in Sweden.
AB  - BACKGROUND: Residential radon is the principal source of exposure to ionizing
      radiation in most countries. To determine the implications for the risk of lung
      cancer, we performed a nationwide case-control study in Sweden. METHODS: The
      study included 586 women and 774 men 35 to 74 years of age with lung cancer that
      was diagnosed between 1980 and 1984. For comparison, 1380 female and 1467 male
      controls were studied. Radon was measured in 8992 dwellings occupied by the study
      subjects at some time since 1947. Information on smoking habits and other risk
      factors for lung cancer was obtained from questionnaires. RESULTS: Radon levels
      followed a log-normal distribution, with geometric and arithmetic means of 1.6
      and 2.9 pCi per liter (60.5 and 106.5 Bq per cubic meter), respectively. The risk
      of lung cancer increased in relation to both estimated cumulative and time
      weighted exposure to radon. In comparison with time-weighted average radon
      concentrations up to 1.4 pCi per liter (50 Bq per cubic meter), the relative risk
      was 1.3 (95 percent confidence interval, 1.1 to 1.6) for average radon
      concentrations of 3.8 to 10.8 pCi per liter (140 to 400 Bq per cubic meter), and
      it was 1.8 (95 percent confidence interval, 1.1 to 2.9) at concentrations
      exceeding 10.8 pCi per liter. The estimates of risk were in the same range as
      those projected from data in miners. The interaction between radon exposure and
      smoking with regard to lung cancer exceeded additivity and was closer to a
      multiplicative effect. CONCLUSIONS: Residential exposure to radon is an important
      cause of lung cancer in the general population. The risks appear consistent with
      earlier estimates based on data in miners.

PMID- 8264738
TI  - The transjugular intrahepatic portosystemic stent-shunt procedure for variceal
      bleeding.
AB  - BACKGROUND: Transjugular placement of an intrahepatic stent is a new technique to
      establish a portosystemic shunt for treatment of portal hypertension. A puncture
      needle is advanced in a catheter through the inferior vena cava into a hepatic
      vein; then an intrahepatic branch of the portal vein is punctured and an
      expandable stent of metallic mesh is implanted to establish the shunt. METHODS:
      We attempted the stent-shunt procedure in 100 of 112 consecutive patients with
      variceal bleeding due to cirrhosis, who were then followed for a mean (+/- SD) of
      12 +/- 6 months. Of the 100 patients, 22 had Child-Pugh class C cirrhosis, 10
      were treated on an emergency basis, and 68 had alcoholic cirrhosis. The shunt was
      established with use of Palmaz stents expanded to 8 to 12 mm in diameter.
      RESULTS: Technical success was achieved in 93 percent of the patients. The mean
      (+/- SD) time for the procedure was 1.2 +/- 0.3 hours. The shunt reduced the
      portal venous pressure gradient by 57 percent. Major complications were
      hemorrhage (intraabdominal bleeding in six patients, biliary bleeding in four,
      and bleeding in the liver capsule in three) and migration of the stent into the
      pulmonary artery (in two patients). At follow-up, stenosis of the shunt was
      evident in 21 patients and occlusion in 10 patients; 10 of these 31 patients had
      variceal rebleeding. Stenoses and occlusions of the shunt were all treated
      successfully by redilation, thrombolysis, or implantation of an additional stent.
      Hepatic encephalopathy (stages I to III) developed in 25 percent of the patients.
      The proportion of patients with shunts who remained free of variceal rebleeding
      was 92 percent at six months and 82 percent at one year. The 30-day mortality was
      3 percent. The cumulative one-year survival was 85 percent. CONCLUSIONS: These
      results suggest that the transjugular placement of an intrahepatic portosystemic
      stent is an effective and safe treatment for variceal hemorrhage in patients with
      portal hypertension due to cirrhosis.

PMID- 8264739
TI  - Brief report: infection of a laboratory worker with simian immunodeficiency
      virus.

PMID- 8264740
TI  - Brief report: Liddle's syndrome revisited--a disorder of sodium reabsorption in
      the distal tubule.

PMID- 8264741
TI  - Images in clinical medicine. Transjugular intrahepatic portosystemic shunt.

PMID- 8264742
TI  - Screening for colorectal cancer by nurse endoscopists.
AB  - BACKGROUND: Case-control studies have demonstrated that screening by
      sigmoidoscopy is effective in reducing mortality from colorectal cancer. If
      nurses performed screening examinations, more patients could be screened and, at
      current income levels, at a lower cost. METHODS: Two registered nurses and two
      licensed practical nurses learned to perform examinations with the flexible
      fiberoptic sigmoidoscope in order to screen patients for colorectal tumors. They
      performed 1881 independent examinations of outpatients more than 45 years of age.
      During the same period, 730 examinations were performed by two
      gastroenterologists in similar patients. RESULTS: The mean depth of insertion of
      the sigmoidoscope was slightly but significantly greater in the patients examined
      by the physicians than in those examined by the nurses (48 vs. 46 cm in men, P =
      0.003; 41 vs. 38 cm in women, P = 0.002). Adenomas were found in 14 percent of
      the men and 8 percent of the women examined (P = 0.001). Nine cancers were found
      in men and four in women. There were no significant differences between the
      nurses and the physicians in the proportion of examinations that were positive
      for adenomas or cancer. No complications occurred during the initial examinations
      or during 894 follow-up sigmoidoscopic procedures. Among the patients whose
      initial examination results were normal, more of those examined by nurses
      returned for follow-up sigmoidoscopy after 12 months or more (45 percent, vs. 30
      percent of those examined by physicians; P = 0.001). CONCLUSIONS: Nurses can
      carry out screening by flexible sigmoidoscopy as accurately and safely as
      experienced gastroenterologists.

PMID- 8264743
TI  - Cerebral palsy.

PMID- 8264744
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 3-1994. An 11-year-old boy with recurrent abdominal pain and
      evidence of pancreatitis.

PMID- 8264745
TI  - Multimodal therapy for solid tumors.

PMID- 8264746
TI  - The side-to-side portacaval shunt revisited.

PMID- 8264747
TI  - Simian immunodeficiency virus in people.

PMID- 8264748
TI  - Preventive care for women--does the sex of the physician matter?

PMID- 8264749
TI  - Preventive care for women--does the sex of the physician matter?

PMID- 8264750
TI  - Preventive care for women--does the sex of the physician matter?

PMID- 8264751
TI  - Preventive care for women--does the sex of the physician matter?

PMID- 8264752
TI  - Heart disease and race.

PMID- 8264753
TI  - Heart disease and race.

PMID- 8264754
TI  - Heart disease and race.

PMID- 8264756
TI  - Hyperthermia.

PMID- 8264755
TI  - Hyperthermia.

PMID- 8264757
TI  - Hyperthermia.

PMID- 8264758
TI  - Hyperthermia.

PMID- 8264759
TI  - Survival after prolonged hypothermia.

PMID- 8264760
TI  - Outpatient treatment of febrile children with sickle cell disease.

PMID- 8264761
TI  - Outpatient treatment of febrile children with sickle cell disease.

PMID- 8264762
TI  - Screening for prostate cancer.

PMID- 8264763
TI  - bcl-2 protein in non-small-cell lung carcinoma.

PMID- 8264765
TI  - Unemployment after health care reform?

PMID- 8264764
TI  - Acute monoarthritis.

PMID- 8264766
TI  - Informed consent, cancer, and truth in prognosis.

PMID- 8264767
TI  - Effect of glucose starvation on germ-tube production by Candida albicans.
AB  - By incubating starved and unstarved yeast cells in synthetic media with a pH of
      4.5 or 6.7 at 37 degrees C the effect of a 3 hours' glucose starvation on germ
      tube production by Candida albicans was evaluated. In addition the endocellular
      content of total carbohydrates, glycogen, trehalose and proteins after and before
      the starvation were dosed. The most interesting result was the overcoming of the
      pH-regulated dimorphism, thanks to the starvation treatment. In fact the starved
      cultures produced germ-tubes indifferently in neutral or acid media, whereas the
      filamentation of the unstarved cultures was more copious in pH 6.7 medium. The
      endocellular content of trehalose and protein was unchanged, whereas total
      carbohydrates and glycogen showed a shortage after the 3 hours' glucose
      starvation. The possible involvements of these metabolic changes in the
      regulation of dimorphic transition are discussed.

PMID- 8264768
TI  - Identification of the perfect state of Cryptococcus neoformans from 195 clinical
      isolates including 84 from AIDS patients.
AB  - Filobasidiella neoformans is the teleomorphic state of Cryptococcus neoformans
      and it is a heterothalic. The purpose of this study was to establish the
      proportions of each mating types (a, alpha) from among 195 strains of C.
      neoformans isolated from clinical material. The culture medium used was sunflower
      agar. Cultures were incubated at 20-22 degrees C for 15 days and observed
      periodically for one month. Non-reactive strains were mated several times with
      different reactive strains. Under these conditions 96.8% of the strains were
      found to be reactors. Among both varieties of C. neoformans, mating type alpha
      was found to have the highest frequency of 95% in the variety neoformans and 84%
      in the variety gattii. These results showed a higher reactivity in comparison
      with other investigators. This difference could be due to the medium used or to
      repeated mating with different reactive tested strains.

PMID- 8264769
TI  - Antibody raised against extracellular proteinases of Sporothrix schenckii in S.
      schenckii inoculated hairless mice.
AB  - Sporothrix schenckii produces two extracellular proteinases, namely proteinase I
      and II. Proteinase I is a serine proteinase, inhibited by chymostatin, while
      proteinase II is an aspartic proteinase, inhibited by pepstatin. Studies on
      substrate specificity and the effect of proteinase inhibitors on cell growth
      suggest an important role for these proteinases in terms of fungal invasion and
      growth. There has, however, been no evidence presented demonstrating that S.
      schenckii produces 2 extracellular proteinases in vivo. In order to substantiate
      the in vivo production of proteinases and to attempt a preliminary serodiagnosis
      of sporotrichosis, serum antibodies against 2 proteinases were assayed using S.
      schenckii inoculated hairless mice. Subsequent to an intracutaneous injection of
      S. schenckii to the mouse skin, nodules spontaneously formed and disappeared for
      a period of 4 weeks. Histopathological examination results were in accordance
      with the microscopic observations. Micro-organisms disappeared during the fourth
      week. Serum antibody titers against purified proteinases I and II were measured
      weekly, using enzyme-linked immunosorbent assay (EIA). As a result, the time
      course of the antibody titers to both proteinases I and II were parallel to that
      of macroscopic and microscopic observations in an experimental mouse
      sporotrichosis model. These results suggest that S. schenckii produces both
      proteinases I and II in vivo. Moreover, the detection of antibodies against these
      proteinases can contribute to a serodiagnosis of sporotrichosis.

PMID- 8264770
TI  - High detection rates of cryptococcal antigen in pulmonary cryptococcosis by Eiken
      latex agglutination test with pronase pretreatment.
AB  - Two different kits for the detection of serum cryptococcal antigen in patients
      with pulmonary cryptococcosis were evaluated. The Eiken test (the Eiken Co.,
      Tokyo), which uses pronase for pretreatment of serum, was compared with the
      Crypto-LA test (International Biological Laboratories, Cranbury, NJ), which did
      not use pronase prior to testing. Cryptococcal antigen was detected in 21 of 23
      patients (91%) with the Eiken test and in only 10 of 23 patients (43%) with the
      Crypto-LA test (p < 0.01 by McNemar test). However, the sensitivity of two tests
      was identical without use of pronase, as both tests could detect as little as
      10(4) cells/ml of Cryptococcus neoformans and 10 ng/ml of capsular polysaccharide
      of C. neoformans. In those serum specimens for which both tests were positive,
      titers were much higher for the Eiken test, but there was a statistically
      significant correlation between the two tests (coefficient correlation 0.79, p <
      0.01). Cryptococcal antigen titer levels measured by the Eiken test correlated
      well with clinical courses. There was one false-positive reaction among 82 sera
      of non-cryptococcal patients. Pronase enhanced the sensitivity of the Eiken test,
      which appeared to be useful in patients with pulmonary cryptococcal disease, and
      its use may prevent unneeded lung biopsies.

PMID- 8264771
TI  - Effects of proteinase inhibitors on the cutaneous lesion of Sporothrix schenckii
      inoculated hairless mice.
AB  - Sporothrix schenckii produces two extracellular proteinases, namely proteinase I
      and II. Proteinase I is a serine proteinase, inhibited by chymostatin. On the
      other hand, proteinase II is an aspartic proteinase, inhibited by pepstatin. The
      addition of either pepstatin or chymostatin to the culture medium did not inhibit
      cell growth, however the addition of both inhibitors strongly inhibited fungal
      growth. Accordingly, this suggested that extracellular proteinases play an
      important role in cell growth and that such cell growth may be suppressed if
      these proteinases are inhibited. In order to substantiate this speculation in
      sporotrichosis, the effects of proteinase inhibitors on the cutaneous lesions of
      mice were studied. Ointments containing 0.1% chymostatin, 0.1% pepstatin and 0.1%
      chymostatin-0.1% pepstatin were applied twice daily on the inoculation sites of
      hairless mouse skin, and the time courses of the lesions examined. The inhibitory
      effect in vivo on S. schenckii was similar to that demonstrated in our previous
      in vitro study. Compared to the control, the time course curve of the number of
      nodules present after the application of either pepstatin or chymostatin was
      slightly suppressed. The application of both pepstatin and chymostatin, however,
      strongly suppressed nodule formation. This study not only confirmed the role of 2
      proteinases of S, schenckii for fungal growth in vivo, but also may lead to their
      use as new topical therapeutic agents.

PMID- 8264772
TI  - Evidence for growth of Sporothrix schenckii on dead but not on living sphagnum
      moss.
AB  - When clinical isolates of Sporothrix schenckii were inoculated onto the apices of
      living or dead sphagnum moss plants maintained under growth chamber conditions,
      populations of the fungus, assessed by standard dilution plate methods, increased
      swiftly up to about 70-fold on moist, dead plants but did not increase on the
      live moss. Light and scanning electron microscopy revealed fungal growth and
      sporulation on and within dead plants, but no evidence of either on live plants.
      These data provide indirect support for the contention that S. schenckii does not
      grow on living sphagnum in bogs, but rather that sporotrichosis epidemics
      associated with sphagnum moss are likely to result from contamination of the dead
      plants at some point(s) in the chain of events during or after harvest. One
      practical implication of our results is that precautions should be taken to
      insure that sphagnum moss is stored dry and that it is not wetted any sooner than
      necessary before use. We also report here improvement of the Mycoses isolation
      medium by an increase in cycloheximide from 400 to 800 mg/l, chloramphenicol from
      50 to 250 mg/l, and the addition of rifampicin at 20 mg/l.

PMID- 8264773
TI  - New milk medium for germ tube and chlamydoconidia production by Candida albicans.
AB  - A new medium consisting of UHT milk, tween 80 and agar is described for the
      development of both germ tube and chlamydoconidia by Candida albicans. In total
      172 isolates from clinical specimens, including C. albicans (112), C.
      guilliermondii (4), C. krusei (3), C. parasilopsis (16). C. tropicalis (28),
      Torulopsis glabrata (6) and Trichosporon beigellii (3), were examined in this
      medium by using the standard method. A higher percentage (98.2%) of germ tube
      production by C. albicans was found in this medium than in undiluted serum
      (90.2%). In addition, only C. albicans was found to be able to produce a high
      percentage of chlamydoconidia (95.5%) after 48 hours' incubation. In comparison
      with the conventional medium, corn meal tween 80 agar (21.4%), this new medium
      gives a significantly higher percentage and abundance of chlamydoconidia
      production. Being simple, cheap and easy to prepare, the new milk medium is
      proposed as very practical in the clinical mycology laboratory.

PMID- 8264774
TI  - In vitro susceptibility of Pityrosporum ovale (Malassezia furfur) to human
      androgenic steroids.
AB  - Cells of Pityrosporum ovale that colonize human pilosebaceous units are
      constantly exposed to cutaneous androgenic steroids. The aim of our study was to
      find out whether P. ovale is susceptible to these hormones. Three strains of P.
      ovale were grown in vitro in the presence of various concentrations of
      testosterone, dehydroepiandrosterone, androstenedione, androstanedione, 5-alpha
      dihydrotestosterone and progesterone (10, 100, and 1000 micrograms/ml; agar
      dilution assays). In addition, three strains of Candida albicans were also
      exposed to equal concentrations of the same androgens. As a result, all P. ovale
      strains were suppressed by 1000 micrograms/ml androstenedione, which was the
      strongest inhibitor. The other androgenic steroids also significantly reduced P.
      ovale growth at different concentrations, depending on the hormone used and the
      strain tested. Progesterone was inhibitory at the highest concentration for one
      P. ovale strain only. Candida albicans was not affected by any of the androgens.
      These findings demonstrate an in vitro susceptibility of P. ovale to high
      concentrations of human androgenic steroids. A relevance of this interaction for
      the in vivo fungus-host relation is not apparent.

PMID- 8264775
TI  - AIDS update: the HIV epidemic: what lies ahead?

PMID- 8264776
TI  - Biological and synthetic materials for the treatment of open wounds and skin
      ulcers.

PMID- 8264777
TI  - [Do you understand a service contract?].
AB  - The aim of this article is to explain to a nurse what she should look for in
      service contracts to enable her to know when a new post is acceptable and how she
      should act within the conditions of the contract. She should also be able to
      distinguish between different types of contracts and know what to look at to
      protect her rights as an employee, or to ensure her service benefits.

PMID- 8264778
TI  - Should AIDS be notifiable?

PMID- 8264779
TI  - Introducing asthma.

PMID- 8264780
TI  - The treatment of TB.

PMID- 8264781
TI  - [Organophosphate poisoning].
AB  - The number of patients admitted to Intensive Care Units with organophosphate
      poisoning are a source of concern. Also distressing is the fact that
      organophosphates are often being used in suicide attempts. It is therefore
      imperative that the nurse acquires and retains the necessary skills for caring
      for these patients. The course of this condition and the associated nursing care
      is discussed at length in this article in an attempt to equip you with these
      skills.

PMID- 8264782
TI  - The challenge of primary health care.

PMID- 8264783
TI  - "Pica".

PMID- 8264784
TI  - Hezekiah's boil.

PMID- 8264785
TI  - Index. Volumes 361-366.

PMID- 8264786
TI  - End of the line for smallpox virus?

PMID- 8264787
TI  - Canadian science gets Nobel gift.

PMID- 8264788
TI  - EU states back biotech patent reforms.

PMID- 8264789
TI  - Old AIDS news dressed up as new.

PMID- 8264790
TI  - Survey battle leads to plagiarism verdict.

PMID- 8264791
TI  - AIDS, HIV and the Sunday Times.

PMID- 8264792
TI  - Neurobiology. Anchoring glycine receptors.

PMID- 8264793
TI  - Obesity. Brown fat and yellow mice.

PMID- 8264794
TI  - Carcinogenesis. Missing mismatch repair.

PMID- 8264795
TI  - Development of obesity in transgenic mice after genetic ablation of brown adipose
      tissue.
AB  - Brown adipose tissue, because of its capacity for uncoupled mitochondrial
      respiration, has been implicated as an important site of facultative energy
      expenditure. This has led to speculation that this tissue normally functions to
      prevent obesity. Attempts to ablate or denervate brown adipose tissue surgically
      have been uninformative because it exists in diffuse depots and has substantial
      capacity for regeneration and hypertrophy. Here we have used a transgenic
      toxigene approach to create two lines of transgenic mice with primary deficiency
      of brown adipose tissue. At 16 days, both lines have decreased brown fat and
      obesity. In one line, brown fat subsequently regenerates and obesity resolves. In
      the other line, the deficiency persists and obesity, with its morbid
      complications, advances. Obesity develops in the absence of hyperphagia,
      indicating that brown fat deficient mice have increased metabolic efficiency. As
      obesity progresses, transgenic animals develop hyperphagia. This study supports a
      critical role for brown adipose tissue in the nutritional homeostasis of mice.

PMID- 8264796
TI  - A role for Fyn tyrosine kinase in the suckling behaviour of neonatal mice.
AB  - Non-receptor-type tyrosine kinases of the Src family, such as Src, Yes and Fyn,
      are strongly expressed in the brain and have been suggested to have an important
      function in the central nervous system. We generated Fyn-deficient mice by
      inserting the beta-galactosidase gene (lacZ) into the fyn gene. The homozygous
      Fyn-mutant neonates from homozygous Fyn-deficient parents died because of a
      suckling problem. Neonates were, however, able to suckle milk normally when the
      homozygous mother's mammary glands had been activated by suckling of a
      heterozygous or wild-type pup. In these homozygous pups, the modified glomerular
      complex of the olfactory bulb, which had been suggested to play a role in
      perceiving pheromones, was abnormal in shape and reduced in size, and the
      hippocampal cell-layer was undulated. These results suggest that Fyn may be
      involved in the initial step of instinctive suckling behaviour in neonates.

PMID- 8264797
TI  - Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal
      neurons.
AB  - Each neuron in the mammalian brain carries many postsynaptic membrane
      specializations containing high densities of receptors that mediate signal
      transduction upon neurotransmitter release from the apposed nerve terminal.
      Little is known about the mechanisms by which receptors are transported to and
      anchored at postsynaptic sites, but extracellular as well as intracellular
      components may be involved. Ultrastructural studies have shown that the
      peripheral membrane protein gephyrin, which co-purifies with the postsynaptic
      inhibitory glycine receptor (GlyR) upon affinity chromatography, is situated on
      the cytoplasmic face of glycinergic postsynaptic membranes. Moreover, gephyrin
      binds with high affinity to polymerized tubulin and has been postulated to link
      the GlyR to the subsynaptic cytoskeleton. Here we report that treatment of rat
      spinal neurons in culture with gephyrin antisense oligonucleotides prevents the
      formation of GlyR clusters in the dendritic plasma membrane. Thus, gephyrin is
      essential for localizing the GlyR to presumptive postsynaptic plasma membrane
      specializations.

PMID- 8264798
TI  - Potential virulence determinants in terminal regions of variola smallpox virus
      genome.
AB  - Smallpox eradication culminated the most successful antimicrobial campaign in
      medical history. To characterize further the linear double-stranded DNA genome of
      the aetiological agent of smallpox, we have determined the entire nucleotide
      sequence of the highly virulent variola major virus, strain Bangladesh-1975 (VAR
      BSH; 186,102 base pairs, 33.7% G + C; Genbank accession number, L22579). Here we
      highlight features of the molecule and focus on a few of the 187 putative
      proteins that probably contribute to pathogenicity and virus host-range
      properties. One hundred and fifty proteins were markedly similar to those of
      vaccinia virus (smallpox vaccine), for which a complete sequence has been
      reported for strain Copenhagen (VAC-CPN; 191,636 base pairs, 33.3% G + C). The
      remaining 37 proteins reflected variola-specific sequences or open reading frame
      divergences for variant proteins, which are often truncated or elongated compared
      with their vaccinia counterparts.

PMID- 8264799
TI  - Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich
      repeats.
AB  - Ribonuclease inhibitor is a cytoplasmic protein that tightly binds and inhibits
      ribonucleases of the pancreatic ribonuclease superfamily. The primary sequence of
      this inhibitor contains leucine-rich repeats (LRRs); these motifs are present in
      many proteins that participate in protein-protein interactions and have different
      functions and cellular locations. In vivo, ribonuclease inhibitor may have a role
      in the regulation of RNA turnover in mammalian cells and in angiogenesis. To
      define the structural features of LRR proteins and to understand better the
      nature of the tight interaction of ribonuclease inhibitor with ribonucleases, we
      have determined the crystal structure of the porcine inhibitor. To our knowledge,
      this is the first three-dimensional structure of a protein containing LRRs and
      represents a new class of alpha/beta protein fold. Individual repeats constitute
      beta-alpha structural units that probably also occur in other proteins containing
      LRRs. The non-globular shape of the structure and the exposed face of the
      parallel beta-sheet may explain why LRRs are used to achieve strong protein
      protein interactions. A possible ribonuclease-binding region incorporates the
      surface formed by the parallel beta-sheet and the beta alpha loops.

PMID- 8264801
TI  - Risk estimates for UV-B-enhanced solar radiation.

PMID- 8264800
TI  - [Lantibiotics, a class of ribosomally synthesized peptide antibiotics].
AB  - Lantibiotics are defined as peptide antibiotics containing the unusual amino
      acids mesolanthionine, 3-methyllanthionine, dehydroalanine, and dehydrobutyrine.
      They are synthesized by some gram-positive bacteria. Their inhibitory effect on
      certain other gram-positive bacteria is explained by detergent-like damage of
      cytoplasmic membranes. Prominent members of the lantibiotics are nisin of
      Lactococcus lactis, which can be used as a food preservative, subtilin of
      Bacillus subtilis, which is similar to nisin, and epidermin of Staphylococcus
      epidermidis, which is considered in the treatment of acne. Lantibiotics are
      ribosomally synthesized as prepeptides, which are posttranslationally modified.
      Genes probably encoding these biosynthetic enzymes and regulatory factors have
      been identified adjacent to the structural genes of the lantibiotics subtilin,
      nisin, and epidermin.

PMID- 8264802
TI  - Electron spin resonance measurements of erythrocytes and hemoglobin stored at 77
      K.

PMID- 8264803
TI  - Nerd, a locus on chromosome III, affects male reproductive behavior in Drosophila
      melanogaster.

PMID- 8264804
TI  - Does aging affect the period of the circadian pacemaker in vertebrates?

PMID- 8264805
TI  - [Polyreactions--mechanisms, taxonomy, relevance].
AB  - Polyreactions are the prerequisite of life and genetics and are also the basis of
      all processes for the production of plastics. In this article, an actualized
      classification of polyreactions based on the reaction mechanism is discussed with
      a differentiation in chain and step polyreactions. Besides the explanation of the
      mechanisms of radical, ionic, and coordination polyreactions, polyaddition and
      polycondensation reactions are covered. In addition, metathesis, polyelimination
      as well as photochemical and radiochemical polyreactions are considered. Finally,
      the influence of the reaction mechanism on the properties of materials and the
      relevance of polyreactions in biology are investigated.

PMID- 8264806
TI  - Changes in seasonality of birth rates in Germany from 1951 to 1990.

PMID- 8264807
TI  - Histochemical localization of NADPH-diaphorase in the adult Drosophila brain. Is
      nitric oxide a neuronal messenger also in insects?

PMID- 8264808
TI  - Chromosome aberrations induced in the lymphocytes of pilots and stewardesses.

PMID- 8264809
TI  - Evans defends JAMA paper on organ acquisition costs, says data misinterpreted.

PMID- 8264810
TI  - Transplant patient receives the gift of life, spends her new life giving to
      others. Interview by Cynthia Knapp Lefton.

PMID- 8264811
TI  - AAKP adopts guidelines on adequacy.

PMID- 8264812
TI  - How the guidelines were developed.

PMID- 8264813
TI  - ACE inhibitor slows onset of renal disease in diabetics by 50%.

PMID- 8264814
TI  - [Hormone therapy as primary therapy of operable breast carcinoma in elderly
      patients].

PMID- 8264815
TI  - [Breast carcinoma 1993].

PMID- 8264816
TI  - [Echography for palpable breast tumors].

PMID- 8264817
TI  - [Periodical screening of families with a hereditary predisposition for breast
      carcinoma].

PMID- 8264818
TI  - [Tumor markers in screening, diagnosis and treatment of patients with breast
      carcinoma].

PMID- 8264819
TI  - [Loco-regional treatment of breast carcinoma].

PMID- 8264821
TI  - [Immediate breast reconstruction following treatment for breast carcinoma].

PMID- 8264820
TI  - [Adjuvant treatment of breast carcinoma].

PMID- 8264822
TI  - [Ultrasonographic study of the palpable breast tumor is very useful].
AB  - OBJECTIVE: To determine the value of ultrasonographic examination in the
      assessment of palpable breast tumours, with special reference to the distinction
      between benign and malignant tumours. DESIGN: Prospective ultrasonographic study;
      the results of the ultrasonographic examination were compared retrospectively
      with those of mammographic examination. SETTING: Diakonessenhuis, Utrecht.
      METHOD: In 282 successive patients, 300 palpable breast tumours were examined
      ultrasonographically in the period from December 1989 to May 1992 and the
      findings were compared with those of morbid-anatomical examination (histological
      examination in solid tumours, cytological examination in cysts). The results of
      ultrasonographic and mammographic examination of 241 tumours were compared.
      RESULTS: Of the 300 palpable tumours examined ultrasonographically, 297 were
      included in the study (122 carcinomas and 175 benign lesions). The sensitivity of
      ultrasonography was 97.5%, its specificity 92.6%. The predictive value of a
      positive test result was 90.2%. When the results of ultrasonography and
      mammography were compared for 204 tumours, the sensitivity of ultrasonography
      proved to be 97.4% and its specificity 91.0%; for mammography, these figures were
      91.3% and 75.3%, respectively. CONCLUSION: Ultrasonography of palpable breast
      tumours can be a highly reliable diagnostic method, particularly with a view to
      distinguishing between malignant and benign lesions.

PMID- 8264823
TI  - [Ultrasonography important as a supplement to mammography].
AB  - The results of three years of diagnostic imaging of the breast were evaluated
      retrospectively, with special attention to the influence of ultrasonography. In
      5245 mammographic investigations, 1841 supplementary ultrasonograms were
      considered necessary (35%). Malignancy of the breast was diagnosed in 250 cases.
      In 131 female patients the histological diagnosis was preceded by a mammography
      and supplementary ultrasonography. In 123 patients a lesion suggestive of
      malignancy could be visualised by ultrasonography (94%). The combined sensitivity
      for detection of malignancy was 97%. Specificity was 98%. Negative predictive
      value was almost 100% and the positive predictive value was 78%, with an observed
      prevalence of malignancy of 7%. To assess the additional value of ultrasound the
      retrospective sensitivity of mammography alone was determined by reviewing the
      mammograms separate from the ultrasonograms of the malignancy-positive patients.
      An increase of sensitivity of at least 15% could be attributed to
      ultrasonography. In 40% of the cases an objective benefit of ultrasonography
      could be established. It is concluded that especially in women with palpable
      lesions whose mammograms are hard to interpret, e.g. young patients with
      extensive glandular tissue or patients with fibrocystic disease, adenofibrosis or
      mastopathy, an additional ultrasonogram is indispensable, not only for diagnosis
      but also for further management of the patient.

PMID- 8264824
TI  - [Revision of consensus statement on imaging diagnosis of the breast].
AB  - Changes which have taken place since 1983, when the Dutch consensus meeting on
      mammography was held, made it necessary to review the consensus statement. In
      1983 only radiologists participated in the working group, in 1993 representatives
      from all other relevant disciplines participated as well. Much attention was paid
      to the indication for mammography and supplementary diagnostic methods,
      especially ultrasound techniques and US-guided cytology. Along the lines given by
      the ACR guidelines on breast cancer reporting, attention was given to better
      communication with referring doctors.

PMID- 8264825
TI  - [Risk factors for the development of recurrences in patients with breast
      carcinoma without axillary lymph node metastases].
AB  - The influence of a number of risk factors on development of tumour recurrence was
      studied retrospectively in a group of breast cancer patients without axillary
      lymph node metastases, all treated identically and with long follow-ups. Of 71
      patients all data could be retrieved. This group had a median duration of follow
      up of five years. Thirteen patients (18.3%) had had a recurrence of carcinoma
      after a median disease-free period of 41 months (range 3-124 months). These
      patients at the time when breast cancer was diagnosed had had a lower median age
      than patients who had remained free of tumour recurrence, 48 (40-70) as against
      59.5 (30-81) years. Factors having a statistically significant prognostic
      importance for recurrence of tumour were age at the time of diagnosis of breast
      carcinoma, histological tumour grade and nuclear DNA content. Identifying groups
      of patients with a higher or lower risk of tumour recurrence appears possible by
      combination of risk factors. Although patients with breast cancer without
      axillary lymph node metastases are supposed to have a favourable prognosis, there
      appear to exist subgroups with a raised risk for development of a recurrence.
      These groups might be prime candidates for prospective randomized studies of the
      usefulness of adjuvant therapy.

PMID- 8264826
TI  - [Role of radiation in the diagnosis and treatment of breast carcinoma].

PMID- 8264827
TI  - [Nursing home care: doing what in earlier days was done differently or not at
      all].

PMID- 8264828
TI  - [Current diagnostic criteria for vascular dementia; milestone or obstacle?].

PMID- 8264829
TI  - [Cartilage lesions of the knee].

PMID- 8264830
TI  - [Long-term results of meniscectomy].

PMID- 8264831
TI  - [Series of articles on nursing home medicine].

PMID- 8264832
TI  - [Typing of methicillin-resistant Staphylococcus aureus strains for
      epidemiological studies using the polymerase chain reaction].
AB  - OBJECTIVE: To determine whether polymerase chain reaction (PCR) fingerprinting
      can be used to gain insight into the epidemiology of methicillin resistant
      Staphylococcus aureus (MRSA). DESIGN: Retrospective DNA analysis of MRSA strains.
      BACTERIAL STRAINS: MRSA strains were collected in two Dutch and one Belgian
      hospital (Reinier de Graaf Gasthuis, Delft; St. Antonius Ziekenhuis, Nieuwegein;
      St. Jan Ziekenhuis, Brugge). METHODOLOGY: MRSA DNA was isolated by standard
      procedures. Differences in genomic organisation were detected with the aid of
      exponential enzymatic synthesis of intrinsically variable DNA domains. This so
      called PCR fingerprinting, a relatively new technique, was performed in direct
      comparison with phage typing. The latter is the current golden standard for S.
      aureus typing. RESULTS: The results of both PCR fingerprinting and phage typing
      appeared to be useful for strain identification. All results were consistent with
      other epidemiological data. CONCLUSION: Genotyping MRSA with PCR fingerprinting
      is complementary to phage typing. In some instances PCR fingerprinting is even to
      be preferred to the other technique. PCR fingerprinting is well suited for the
      analysis of MRSA spreading.

PMID- 8264833
TI  - [Carrier state and spread of methicillin resistant Staphylococcus aureus
      following hospital discharge].
AB  - OBJECTIVE: To determine whether patients colonised with methicillin-resistant
      Staphylococcus aureus (MRSA) remain carriers after discharge from hospital and
      whether transmission of MRSA to the community occurs. DESIGN: Prospective and
      retrospective study. PATIENTS AND METHODS: Fifteen patients colonized with MRSA
      and admitted to the University Hospital of the University of Amsterdam between
      January 1991 and September 1992 were screened for MRSA after their discharge from
      hospital (350 days median). Their family members and domestic animals were
      screened at the same time. RESULTS: Cultures from 50 people (15 ex-patients, 35
      family members) and II animals were investigated for presence of MRSA. Two (13%;
      95% confidence interval: 2-40%) patients still carried the MRSA strain. Both
      still had risk factors for carriage of the bacteria. No MRSA was found in
      cultures from family members or domestic animals. CONCLUSIONS: Long term carriage
      of MRSA outside the hospital occurs infrequently and is closely related to
      predisposing factors of the patient. Transmission of MRSA to healthy individuals
      could not be demonstrated.

PMID- 8264834
TI  - [Liver rupture in a newborn infant; diagnosis, treatment and prognosis].
AB  - Between August 1989 and August 1992 four neonates with rupture of the liver were
      admitted to the Neonatal Intensive Care Unit of the Sophia Children's Hospital in
      Rotterdam, the Netherlands. Two neonates were born after breech delivery, two
      after caesarean section because of foetal distress. All four patients had Apgar
      scores < 5 after 1 minute and of < 8 after 5 minutes and required artificial
      ventilation for a prolonged period. All infants collapsed within 6 hours after
      birth. Surgical treatment was not considered because of the poor clinical
      condition. All patients were treated conservatively. Clinical signs were: rapid
      onset pallor, hypotension, tachycardia and abdominal distension. Ultrasonography
      of the abdomen confirmed the clinical diagnosis of rupture of the liver. Despite
      rapid diagnosis and maximal non-surgical treatment mortality was 75%. Surgical
      intervention is indicated in neonatal liver rupture with significant intra
      abdominal bleeding.

PMID- 8264835
TI  - [Traumatic carotid artery stenosis with cerebral infarct].
AB  - After an accident causing a wound beside the larynx a 17-year-old male was
      diagnosed as having a cerebral haemorrhagic contusion. He was treated
      conservatively, when six weeks later uncertainty about the diagnosis prompted
      angiography of the common carotid arteries. The diagnosis had to be revised: a
      traumatic occlusion of the carotid artery. The patient's favourable recovery was
      credited to development of a good collateral circulation to which his relative
      youth contributed. Traumatic occlusion of the carotid artery should be considered
      when neurological disorders are apparent but the patient is conscious, especially
      when there is a symptom-free interval.

PMID- 8264836
TI  - [Professional education as nursing home physician. I. Development and
      organization].

PMID- 8264837
TI  - [Professional education as nursing home physician. II. Starting points and
      content].

PMID- 8264838
TI  - [Consensus asthma in children].

PMID- 8264839
TI  - [Consensus asthma in children].

PMID- 8264840
TI  - [Consensus asthma in children].

PMID- 8264841
TI  - [Post-pharyngitis sepsis caused by Fusobacterium necrophorum: Lemierre syndrome].

PMID- 8264842
TI  - [Minor symptoms in family medicine; superficial skin burns].

PMID- 8264843
TI  - Increased arginine vasopressin secretion may participate in the enhanced
      susceptibility of Lewis rats to inflammatory disease.
AB  - Lewis (LEW/N) and Fisher (F344/N) rats are histocompatible inbred strains
      characterized respectively by susceptibility and resistance to inflammatory
      disease. LEW/N rats have deficient corticotropin-releasing hormone (CRH), ACTH
      and corticosterone responses to inflammation, and increased circulating and
      hypothalamic concentrations of arginine vasopressin (AVP). CRH is produced
      locally at inflammatory sites, where it acts as a proinflammatory agent, while
      AVP has been reported to exert immunopotentiating effects in vivo and in vitro.
      In order to further investigate the mechanism of increased AVP secretion in LEW/N
      rats, we measured AVP and CRH mRNA in several hypothalamic nuclei in LEW/N and
      F344/N rats, using in situ hybridization histochemistry. LEW/N rats had increased
      AVP mRNA concentrations in the supraoptic (SON) and paraventricular (PVN), but
      not in the suprachiasmatic (SCN) nuclei. CRH mRNA, on the other hand, was
      decreased in the PVN of LEW/N rats. To examine the potential role of AVP and CRH
      in the exaggerated inflammatory responses of LEW/N rats, we pretreated young
      female Lewis and Fischer rats with AVP- and/or CRH-neutralizing rabbit antisera
      and elicited subsequently an inflammatory response by a nuchal subcutaneous
      injection of carrageenin. We demonstrated that both antisera decreased
      significantly the leukocyte concentration in the inflammatory exudate in LEW/N
      rats, but found no synergistic or addictive effects between them. We conclude
      that previously observed differences in hypothalamic AVP and CRH contents between
      LEW/N and F344/N rats correspond to differences in the steady state mRNA levels
      of the two neuropeptides and that both AVP and CRH participate in the excessive
      inflammatory response of Lewis rats as locally active proinflammatory agents.

PMID- 8264844
TI  - Effect of endotoxin on pituitary hormone secretion in sheep.
AB  - Endotoxin, a potent stimulator of the immune system and an important mediator in
      the pathophysiology of septic shock, has been shown to alter the release of
      certain hormones following its systemic administration. The purpose of this study
      was to determine the effects of endotoxin on pituitary hormone secretion both in
      vivo and in vitro in sheep, with emphasis placed on its effects on growth hormone
      (GH) release. Endotoxin (400 ng/kg i.v.) increased plasma GH, adrenocorticotropic
      hormone (ACTH), cortisol and prolactin, while it decreased luteinizing hormone
      (LH) pulse frequency (p < 0.05). Plasma levels of tumor necrosis factor, a major
      mediator of endotoxin effects, also increased following endotoxin administration.
      Endotoxin did not affect the GH response to human GH-releasing hormone. In vitro
      studies evaluated the effect of endotoxin to alter GH secretion from dispersed
      sheep anterior pituitary cells at dosages of 1, 10 and 50 micrograms/ml, with
      samples collected at 4, 8 and 24 h. Endotoxin increased pituitary GH secretion at
      24 h for 1 microgram/ml (p < 0.05) and at all time periods for 10 and 50
      micrograms/ml (p < 0.05). It also led to an increased release of ACTH and LH in
      vitro. The results of this study demonstrate the ability of endotoxin to alter
      pituitary hormone secretion both in vivo and in vitro in sheep, suggesting a
      direct effect of endotoxin on the pituitary gland.

PMID- 8264845
TI  - Endotoxin- and corticotropin-releasing hormone-induced release of ACTH and
      cortisol. A comparative study in men.
AB  - The present study compares the effects of endotoxin, a key factor in gram
      negative bacterial infection, and of corticotropin-releasing hormone (CRH) on
      ACTH and cortisol secretion in healthy male volunteers in a placebo-controlled
      design. Endotoxin (isolated from Salmonella abortus equi; 0.4 ng/kg body weight)
      induced a significantly delayed and prolonged increase of ACTH and cortisol
      secretion as compared to CRH (100 micrograms), supporting the hypothesis that
      different intermediate mechanisms are involved (baseline/peak: ACTHEndotoxin vs.
      ACTHCRH: 140 +/- 40 min vs. 44 +/- 17 min (p < 0.001); CortisolEndotoxin vs.
      CortisolCRH: 113 +/- 51 min vs. 66 +/- 31 min (p < 0.05); peak/baseline:
      ACTHEndotoxin vs. ACTHCRH: 244 +/- 79 min vs. 200 +/- 25 min (p < 0.05);
      CortisolEndotoxin vs. CortisolCRH: 278 +/- 76 min vs. 182 +/- 16 min (p <
      0.001)). Activation of the hypothalamo-pituitary-adrenocortical (HPA) system by
      endotoxin in men is associated with increased interleukin-6 (peak value: 124 +/-
      109 pg/ml) and tumor necrosis factor-alpha (peak value: 69 +/- 53 pg/ml) plasma
      levels which, probably together with locally produced interleukin-1, stimulate
      the HPA system both at the hypothalamic and (to a lesser degree) at the pituitary
      site. Provided that strictly controlled laboratory conditions are applied, the
      endotoxin challenge test presented here may serve as an appropriate and safe tool
      to explore an individual's capacity for neuroendocrine adaptation to a bacterial
      stressor, thus providing information complementary to the CRH test.

PMID- 8264846
TI  - Direct anterior pituitary modulation of gonadotropin secretion by neuropeptide Y:
      role of gonadal steroids.
AB  - Neuropeptide Y (NPY) acts at the hypothalamus to stimulate LH secretion through
      increased LHRH secretion. NPY is also cosecreted into the portal system in a
      pulsatile manner with LHRH and may act at the anterior pituitary to increase LH
      secretion through potentiation of LHRH responsiveness and possibly through direct
      stimulation; however, controversy exists concerning this direct action of NPY at
      the pituitary. Utilizing dispersed anterior pituitary monolayer cell cultures,
      the first goal of this study was to determine the effects of vehicle, 10(-10) M
      LHRH, 10(-7) M NPY, 10(-6) M NPY, 10(-10) M LHRH + 10(-7) M NPY, and 10(-10) M
      LHRH + 10(-6) M NPY on LH and FSH responsiveness. Under these conditions, 10(-6)
      M NPY alone significantly stimulated LH secretion (630% above basal) and both 10(
      7) M NPY and 10(-6) M NPY significantly potentiated LHRH-induced LH secretion
      (195 and 244% above LHRH alone, respectively). Neither 10(-7) M NPY nor 10(-6) M
      NPY alone stimulated FSH secretion; however, both 10(-7) M and 10(-6) M NPY
      significantly potentiated LHRH-induced FSH secretion (130 and 135% above LHRH
      alone, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264847
TI  - Chronic administration of muscimol and pentobarbital decreases gonadotropin
      releasing hormone mRNA levels in the male rat hypothalamus determined by
      quantitative in situ hybridization.
AB  - The role of GABA in the control of gonadotropin-releasing hormone (GnRH)
      secretion is still controversial. In order to investigate the role of the
      GABAergic system in the regulation of GnRH gene expression in the rat brain, we
      studied the effects of chronic administration (2 days) of the GABAA receptor
      agonist muscimol and the central-type barbiturate receptor agonist pentobarbital
      on GnRH mRNA levels measured by in situ hybridization. Treatment with
      pentobarbital produced a 24% decrease in the hybridization signal. Similarly,
      muscimol treatment decreased the signal by 28%. The concomitant administration of
      the two GABAA receptor agonists resulted in a decrease (37%) of mRNA levels which
      was significantly more marked than that induced by pentobarbital or muscimol
      alone. The present results, together with previous data, indicate that the
      administration of pentobarbital or muscimol can inhibit not only the release of
      GnRH but also the gene expression of the neuropeptide as evaluated by mRNA level
      measurements.

PMID- 8264848
TI  - Suckling and cold stress rapidly and transiently increase TRH mRNA in the
      paraventricular nucleus.
AB  - Thyrotropin releasing hormone (TRH) is released from the median eminence in
      response to neural stimuli evoked by different physiologic conditions (i.e. cold
      stress or suckling). The paraventricular nucleus (PVN) synthesizes pro-TRH and
      responds to negative thyroid hormone feedback. With the aim of determining if TRH
      biosynthesis is regulated in coordination with its release, we quantified TRH
      mRNA levels in PVN and in preoptic area-anterior hypothalamus (POA-AH) of rats
      sacrificed at different times during cold (0.5, 1, 2 or 6 h) or suckling (15, 30
      and 60 min) stimulus; TRH-like immunoreactivity (TRH-LI) in medial basal
      hypothalamus (MBH) and in POA-AH as well as corticosterone, triiodothyronine and
      prolactin levels in serum were also measured. Increases of serum hormones were
      observed in both paradigms as has been reported. MBH TRH-LI content decreased
      during suckling by 33% (p < 0.01) after 1 h, but did not change after cold
      stimulation. At short stimulation times, PVN TRH mRNA levels were 85% (30 min of
      suckling) and 97% (1 h in the cold) higher than their respective controls,
      decreasing to normal after 1-2 h. In the POA-AH, another TRH synthesizing region
      not involved in TRH hypophysiotropic function, a similar transient enhancement of
      TRH mRNA (146%) was observed only in cold stimulated animals after 30 min,
      consistent with its suggested role in thermogenesis. These results show a fast
      and transient response of TRH mRNA in PVN evoked by a neural stimulus.

PMID- 8264849
TI  - A partial blockade of catecholaminergic neurotransmission with 6-hydroxydopamine
      decreases mRNA level of gonadotropin releasing hormone in the male rat
      hypothalamus.
AB  - Central catecholamines (CA) are known to be involved in the regulation of
      synthesis and secretion of gonadotropin releasing hormone (GnRH) from the
      hypothalamus. However, no attempt has been yet made to determine whether CA
      affects GnRH gene expression. To this end, the effect of 6-hydroxydopamine (6
      OHDA), a catecholaminergic neurotoxin, on GnRH mRNA level was examined.
      Hypothalamic tissues obtained from adult male rats were incubated with medium
      containing 6-OHDA. To ensure the effect of 6-OHDA on CA depleting action, CA
      levels in media and in postincubation tissues were determined. Increasing
      concentrations of 6-OHDA resulted in decrease in norepinephrine (NE) and dopamine
      (DA) contents in a dose dependent manner. Treatment with 6-OHDA (5 x 10(-4) M
      produced a time-dependent decrease in NE but not DA, when CA levels in media were
      determined at 30 min intervals during the incubation period. To determine changes
      in GnRH mRNA level in response to 6-OHDA treatment in vitro, for 2.5 h total
      cytoplasmic RNA fractions were isolated from postincubation hypothalamic tissues
      and used for RNA-blot hybridization with 32P-labeled GnRH riboprobe. A blockade
      of CA neurotransmission with 6-OHDA (5 x 10(-4) M) significantly reduced GnRH
      mRNA level by half over its control and internal control (actin mRNA) groups.
      Northern blot analysis revealed that addition of NE (1 x 10(-6) M) reversed the
      decreased GnRH mRNA level by 6-OHDA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264850
TI  - Sex and estrous cycle variations of rat striatal dopamine uptake sites.
AB  - The reuptake of dopamine into nerve terminals is the primary mechanism of
      inactivation of this neurotransmitter in the synaptic cleft. We report sex
      differences and estrous cycle variations of rat striatal dopamine uptake sites.
      During the estrous cycle, peak density of striatal dopamine uptake sites labelled
      with [3H]GBR-12935 occurred in the morning of proestrus in coincidence with peak
      dopamine, serotonin, dihydroxyphenylacetic acid and 5-hydroxytryptophan levels
      pointing to a presynaptic effect of gonadal hormones. Striatal homovanillic acid
      and 5-hydroxyindoleacetic acid levels as well as [3H]GBR-12935 binding affinity
      remained unchanged throughout the estrous cycle. The density of [3H]GBR-12935
      striatal binding sites was lower in ovariectomized rats compared to intact female
      rats during the estrous cycle, whereas it was similar in gonadectomized male
      rats, intact male rats and ovariectomized rats. Binding affinity was in general
      similar for all the groups of rats examined. The affinity of dopamine for
      striatal [3H]GBR-12935 binding sites was similar in males and ovariectomized
      females, and did not change during the female estrous cycle. In summary, striatal
      dopamine uptake site density was lower in male compared to intact female rats and
      was shown to fluctuate during the female estrous cycle. These results suggest
      that gonadal hormones could influence the activity of psychoactive drugs acting
      on neuronal dopamine uptake sites.

PMID- 8264851
TI  - Downregulation of protein kinase C levels leads to inhibition of GnRH-stimulated
      gonadotropin secretion from dispersed pituitary cells of goldfish.
AB  - We have previously shown that the abilities of the two native goldfish GnRHs,
      salmon GnRH (sGnRH) and chicken GnRH II (cGnRH II), to stimulate gonadotropin
      (GtH) secretion and elevate intracellular Ca2+ levels are mimicked by the protein
      kinase C (PKC) stimulators, 1,2-dioctanoylglycerol (DiC8) and 12-O-tetradecanoyl
      phorbol-13-acetate (TPA). The ability of PKC inhibitors to attenuate GnRH
      stimulated GtH secretion was also demonstrated. In the present study, the
      involvement of PKC was examined through the reduction of cellular PKC levels by
      prolonged preincubation of the cells with TPA (TPA desensitization). TPA
      pretreatment reduced the levels of PKC in fish pituitary cells as measured by
      immunoblotting (Western blot). Pretreatment of dispersed goldfish pituitary cells
      in static culture with TPA abolished the GtH responses to sGnRH, cGnRH II and
      ionomycin, and drastically reduced TPA- and DiC8-stimulated GtH release, but had
      no major effect on forskolin-induced GtH release. TPA pretreatment also reduces
      the cell content of GtH in goldfish pituitary cells. Interestingly, treatment
      with all of the pharmacological secretagogues tested led to a decrease in
      cellular contents of GtH, however, the two native GnRHs had no such effect. In
      rapid column perifusion experiments (1-min fractions), the GtH responses induced
      by both native GnRHs were characterized by an initial acute increase in hormone
      secretion followed by a 'plateau' phase which is smaller in magnitude relative to
      the initial phase. TPA pretreatment of perifused cells greatly reduced both the
      peak and plateau phases of sGnRH- and cGnRHII-stimulated GtH secretion;TPA
      induced GtH release is also greatly attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264852
TI  - A possible role of neuropeptide Y in the control of the onset of puberty in
      female rhesus monkeys.
AB  - The onset of puberty is heralded by an increase in pulsatile LHRH release. Since
      neuropeptide Y (NPY) has been implicated as a major regulator in the control of
      pulsatile LHRH release in mature monkeys, we have hypothesized that maturational
      changes in the NPY neuronal system play an important role in puberty. To test
      this hypothesis, three experiments were conducted in female rhesus monkeys using
      a push-pull perfusion method. In the first experiment, changes in NPY release in
      the stalk-median eminence (S-ME) during puberty were determined in 9 prepubertal,
      7 early pubertal and 8 midpubertal monkeys. NPY and LHRH levels were measured in
      aliquots of the same perfusate samples obtained from the S-ME. NPY release was
      pulsatile in all three groups. Mean NPY release and pulse frequency increased
      significantly from the prepubertal through the midpubertal stage. These
      developmental changes in NPY release were parallel to those observed for LHRH
      release in the same monkeys. In order to examine whether NPY infusion into the S
      ME influences LHRH release during puberty, in the second experiment, NPY (10(-6)
      or 10(-8) M) or vehicle was infused into the S-ME for 10 min at 90-min intervals
      in 5 prepubertal and 9 midpubertal monkeys. In the midpubertal stage, infusion of
      NPY at doses of 10(-8) and 10(-6) M resulted in significant (p < 0.01) increases
      in LHRH release, while vehicle administration had no effect. In contrast, in
      prepubertal monkeys, neither NPY nor vehicle infusion altered LHRH release. In
      order to test whether endogenous NPY plays a role in the maintenance of pulsatile
      LHRH release, in the third experiment, a specific antiserum to NPY (aNPY) was
      infused into the S-ME of 6 prepubertal and 8 midpubertal monkeys. Infusion of
      aNPY (1:100, 1:1,000 dilution) significantly suppressed LHRH release in
      midpubertal but not prepubertal monkeys. The results are summarized as follows.
      (1) In prepubertal monkeys, NPY release is low, and the presence of NPY in the S
      ME does not influence LHRH release. (2) At the onset of puberty, NPY release
      begins to increase, and NPY probably starts to stimulate LHRH release. (3) In the
      midpubertal period, NPY release increases further, and NPY in the S-ME is highly
      stimulatory to LHRH release.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8264853
TI  - Ovarian involvement in the suppression of luteinizing hormone in the incubating
      turkey (Meleagris gallopavo).
AB  - A series of experiments were conducted to elucidate the role of the ovary in
      incubation behavior-associated luteinizing hormone (LH) suppression. Ovariectomy
      (Ovx) increased (p < 0.05) serum LH levels in nonphotostimulated, laying and
      photorefractory turkeys but not in incubating birds (p > 0.05). Ovx had no effect
      on intramuscularly injected mammalian luteinizing hormone-releasing hormone (4
      micrograms/kg i.m.)-induced LH in incubating hens, but enhanced the LH response
      in laying hens. Serum LH and prolactin (Prl) were unaffected by Ovx, and nest
      deprivation (ND) decreased Prl levels (p < 0.05) with no effect on serum LH of
      incubating turkeys. However, serum LH increased (p < 0.05) and Prl decreased in
      Ovx-ND birds. Prl mRNA abundance (11.9 +/- 1.2 ng/microgram total RNA) decreased
      following Ovx (3.4 +/- 0.4 ng/microgram total RNA) or ND (3.6 +/- 0.5
      ng/microgram total RNA). Nest deprivation increased LH beta mRNA (2.5-fold) which
      was further increased (4.8-fold) by Ovx. Hypothalamic GnRH-I and GnRH-II contents
      increased (p < 0.05) in Ovx-ND turkeys. We conclude that serum LH suppression
      during incubation behavior requires ovarian participation acting synergistically
      with elevated Prl and/or nesting stimulus on hypothalamic GnRH, and that the
      concentration fo LH beta mRNA may be a limiting factor in LH secretion.

PMID- 8264854
TI  - Contrasting effects of central alpha-1-adrenoreceptor activation on stress
      responsive and stress-nonresponsive subpopulations of corticotropin-releasing
      hormone neurosecretory cells in the rat.
AB  - Stimulation of the rat hypothalamopituitary-adrenal axis during stress involves
      activation of central alpha 1-adrenergic receptors. The subpopulation of
      corticotropin-releasing hormone (CRH) neurosecretory cells that contains
      vasopressin (VP) is selectively activated by several types of stress
      (immobilization, hypoglycemia, and intracerebroventricular, i.c.v., colchicine),
      and is located in a catecholamine-rich area of the hypothalamic paraventricular
      nucleus. Therefore, we tested the hypothesis that the CRH+/VP+ subpopulation is
      selectively activated by central alpha 1-adrenergic receptors. The alpha 1
      agonist methoxamine or vehicle alone was injected i.c.v. after habituation of
      rats to daily injections of vehicle through a chronic i.c.v. cannula. Activation
      of the CRH+/VP+ and CRH+/VP- subpopulations was measured by quantifying depletion
      of neurosecretory vesicles from immunocytochemically identified axons in the
      external zone of the median eminence. The habituated, vehicle-injected sham
      control group had normal levels of plasma ACTH and corticosterone, but possessed
      a significantly higher proportion of VP-containing CRH axons than naive animals.
      This change is similar to what was observed previously in rats subjected to
      repeated daily stress. I.c.v. methoxamine caused elevations of plasma ACTH and
      corticosterone and significant depletions of vesicles from the CRH+/VP+ axons at
      1 and 2 h after injection, compared to the sham control group. The CRH+/VP-
      axons, however, displayed significant accumulations of neurosecretory vesicles at
      the same times after 300 micrograms methoxamine, compared to the sham control
      group. After 100 micrograms methoxamine, there was no change in the CRH+/VP-
      axons, compared to the sham control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264855
TI  - Glucocorticoid feedback regulation of adrenocortical responses to neural stimuli:
      role of CRF-41 and corticosteroid type I and type II receptors.
AB  - In the present study we characterized the negative feedback effect of exogenous
      and endogenous glucocorticoids (GC) on the responses of the hypothalamo-pituitary
      adrenal (HPA) axis to neural stimuli in male rats. Dexamethasone (Dex) was
      injected intraperitoneally at a dose of 0.5-4.0 micrograms/100 g BW and rats were
      exposed to photic or acoustic stress 3.5 h later. The serum ACTH and
      corticosterone (CS) responses to these stimuli were inhibited in a dose-dependent
      manner by Dex, such that the stress-induced response was completely abolished at
      a Dex dose of 4.0 micrograms/100 g BW. Injection of Dex (4.0 micrograms/100 g BW
      i.p.) did not affect the content of CRF-41 at the median eminence under basal
      conditions but prevented the depletion in CRF-41 content following acoustic and
      photic stimulation observed in vehicle-treated animals. Pretreatment with a
      subcutaneous injection of corticosteroid type I receptor antagonist RU-28318 (5
      mg/100 g BW) did not affect the inhibition of the stress-induced adrenocortical
      response exerted by Dex; in contrast the type II receptor antagonist RU-38486 (5
      mg/100 g BW) completely abolished the inhibitory effect of Dex following both
      types of neural stimuli. To investigate the role of type I and type II
      corticosteroid receptors in mediating the feedback effect of endogenous GC, the
      two receptor antagonists were injected intracerebroventricularly (100 ng/100 g
      BW). RU-28318 did not affect the response to photic stress at 10, 30 or 90 min
      following the stress, whereas RU-38486 caused a significant increase
      (approximately 40%) in serum ACTH and CS at all three time points
      tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264856
TI  - Short inescapable stress produces long-lasting changes in the brain-pituitary
      adrenal axis of adult male rats.
AB  - Recently, we reported that rats exposed to a single and short session of
      inescapable footshocks showed alterations in behavioural response to
      environmental stimuli which developed progressively over a week and remained
      present for at least 28 days. The aim of the present study was to investigate
      whether these behavioural changes were accompanied by alterations in the brain
      pituitary-adrenal axis. Male Wistar rats were subjected to 10 inescapable
      footshocks (S) of 6 s duration and 1 mA intensity during a period of 15 min.
      Control rats (C) were placed in the shock apparatus for 15 min without receiving
      shocks. The effects of these experimental procedures were studied 14 days later.
      Exposure to shocks did not affect basal plasma levels of adrenocorticotropic
      hormone (ACTH) and corticosterone (CORT). However, the novelty-induced ACTH
      response was increased in S rats as compared to C rats whereas the CORT response
      did not differ between C and S rats. The ACTH content of the anterior pituitary
      gland and adrenal weight were not affected by exposure to inescapable footshocks
      14 days earlier. Quantitative immunocytochemistry of vasopressin (AVP) and
      corticotropin-releasing factor (CRF) in the external zone of the median eminence
      showed that prior footshock exposure increased the AVPi stores to 167% as
      compared to C rats, whereas CRFi content was not changed. In addition, S rats
      showed increased mineralocorticoid (MR) and glucocorticoid (GR) receptor binding
      capacity in the hippocampus as compared to C rats, whereas affinities were not
      affected. We conclude that a single and short session of inescapable footshocks
      has long-lasting effects on brain-pituitary-adrenal functioning concomitant with
      behavioural alterations.

PMID- 8264857
TI  - Investigation of the role of 5-HT3 receptors in the secretion of prolactin, ACTH
      and renin.
AB  - The potential roles of central and peripheral 5-HT3 receptors in the secretion of
      prolactin, adrenocorticotropic hormone (ACTH), corticosterone and renin was
      investigated. Male rats received the 5-HT3 antagonist ondansetron (0, 0.1 or 1
      mg/kg i.p.), 30 min prior to injections of the serotonin (5-HT) releaser, p
      chloroamphetamine (PCA; 0, 3 or 8 mg/kg i.p.). Blood samples were collected 60
      min after PCA for radioimmunoassays of plasma prolactin, ACTH, corticosterone and
      renin concentrations. PCA significantly elevated secretion of each of these
      hormones. Pretreatment with the 5-HT3 antagonist, ondansetron, significantly
      attenuated the PCA-induced elevation of prolactin secretion, suggesting that 5
      HT3 receptors contribute to the serotonergic stimulation of prolactin secretion.
      Ondansetron did not modify effects of PCA on ACTH, corticosterone or renin
      secretion. To determine whether the 5-HT3 receptor role in prolactin secretion is
      mediated in the brain, the endocrine effects of intracerebroventricular (i.c.v.)
      injections of 5-HT (30 micrograms/kg) or the 5-HT3 agonist, 2-methylserotonin (1,
      20 or 200 micrograms/kg) were evaluated. Both 5-HT and 2-methylserotonin
      significantly elevated plasma prolactin levels 15 min postinjection. However,
      ondansetron (1 mg/kg i.p.) did not antagonize these actions. Both 5-HT and 2
      methylserotonin also increased plasma ACTH and corticosterone concentrations.
      Finally, 5-HT suppressed, while 2-methylserotonin stimulated renin secretion.
      None of the hormonal effects of i.c.v. injected 5-HT or 2-methylserotonin were
      altered by ondansetron. Thus, the results suggest that peripheral, but not
      central 5-HT3 receptors are involved in the stimulation of prolactin secretion.
      Furthermore, 5-HT3 receptors do not mediate the serotonergic stimulation of ACTH,
      corticosterone, or renin secretion.

PMID- 8264858
TI  - Effects of cholecystokinin octapeptide on the hypothalamic-pituitary-adrenal axis
      function and on vasopressin, prolactin and growth hormone release in humans.
AB  - Cholecystokinin (CCK), a gastrointestinal (GI) hormone, is also present in
      structures of the central nervous system such as cortex, hippocampus, amygdala,
      olfactory tubercle and in regions involved in the regulation of the pituitary
      function. Although a number of studies have evaluated the effects of CCK on
      hypothalamic-pituitary-adrenal (HPA) axis function and on arginine vasopressin
      (AVP), prolactin (PRL) and growth hormone (GH) plasma levels in the laboratory
      animal, its role in humans has not been explored. Hence, we examined the effects
      of the exogenous administration of this GI hormone on corticotropin-releasing
      hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, AVP, PRL and GH
      plasma levels in humans. To accomplish this, graded doses (0, 50, 140 and 420
      ng/kg) of sulfated CCK octapeptide (CCK-8), the full biologically active peptide,
      were infused intravenously to healthy men in 30 min. Blood samples were collected
      30 min and immediately before the infusion was started (baseline) and 15, 30, 45,
      60 and 90 min thereafter. CRH, ACTH, and AVP were extracted from plasma proteins
      using cartridges of SepPak C18. These hormones and cortisol were measured by
      radioimmunoassay whereas PRL and GH were measured by immunoradiometric assay. CCK
      8 increased plasma ACTH and cortisol levels only at the dose of 420 ng/kg,
      whereas it had no detectable effect on plasma CRH levels. It increased also
      plasma AVP levels at the doses of 140 and 420 ng/kg. However, this effect reached
      the statistical significance only at the highest dose tested. CCK-8 stimulated
      PRL and GH release in a dose-dependent fashion. The lowest stimulatory dose was
      140 ng/kg for both hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264859
TI  - Gene expression of KA type and NMDA receptors and of a glycine transporter in the
      rat pineal gland.
AB  - This study, using in situ hybridization histochemistry, revealed the pineal gland
      strongly expressed mRNAs of kainic acid-type receptors, N-methyl-D-aspartate
      receptors and the glycine transporter. These findings demonstrated the presence
      of dense glutamatergic innervation of the pineal gland.

PMID- 8264860
TI  - Dual action of GABAA receptors on the secretory process of melanotrophs of
      Xenopus laevis.
AB  - The effects of GABAa receptor activation on the secretion of alpha-melanocyte
      stimulating hormone (alpha-MSH) from the superfused pars intermedia of the
      amphibian Xenopus laevis were examined. The GABAa receptor agonist isoguvacine
      inhibited secretion of alpha-MSH from the pars intermedia, an action completely
      antagonized by the chloride channel blocker picrotoxin. Isoguvacine stimulated
      secretion from picrotoxin-treated tissue. Both effects were blocked by the GABAA
      receptor antagonist bicuculline, indicating that it is a specific action via the
      GABAA receptor. We conclude that, besides the inhibitory chloride channel, there
      is a stimulatory signaling property associated with the GABAA receptor.
      Isoguvacine stimulated the production of c-AMP, an action that was not blocked by
      picrotoxin. This suggests that the stimulatory mechanism of the GABAA receptor
      involves, directly or indirectly, the generation of c-AMP.

PMID- 8264861
TI  - Inhibitory effect of a highly potent antagonist of LH releasing hormone (SB-75)
      on the pituitary gonadal axis in the intact and castrated rat.
AB  - The biological potency of the new, highly potent antagonist [AC-D-Nal (2)1, D
      Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10] LH-RH (SB-75) on the pituitary-gonadal
      system of female castrated and intact ovulating rats was tested. Administration
      of a single dose (50-100 micrograms/kg BW) of the antagonist SB-75 inhibited
      effectively the elevated gonadotrophin levels for 48 h. Pituitary LH and FSH
      content was not affected by SB-75 treatment. When administered in the early
      afternoon of the proestrus to intact cycling rats, SB-75 blocked the preovulatory
      LH surge as well as the primary and secondary FSH surges. However, the secondary
      FSH surge was not affected by SB-75 treatment when administered on the evening of
      proestrus suggesting its independence from the LH-RH mechanism. A group of
      ovariectomized rats was chronically treated with D-Trp6-LH-RH after having been
      pretreated by administration of a single dose of the antagonist. The initial
      stimulatory release of LH and FSH initiated by injection of the LH-RH agonist was
      significantly reduced by pretreatment with the LH-RH antagonist. We conclude that
      the LH-RH antagonist SB-75 may be used effectively in the field of reproductive
      dysfunction and endocrinological oncology and may become an invaluable
      physiological probe in studying the hormonal dynamics of the reproductive
      endocrine axis.

PMID- 8264862
TI  - Secretion of specific nonphosphorylated and phosphorylated rat prolactin isoforms
      at different stages of the estrous cycle.
AB  - The biological activity and immunoreactivity of serum prolactin (PRL) has been
      shown to fluctuate throughout the estrous cycle of the rat. Since the 24-kDa
      nonphosphorylated and phosphorylated isoforms from several species have also been
      shown to differ in their biological and immunoreactivities, we have investigated
      the possibility that the 24-kDa monomer isoform profile varied throughout the
      estrous cycle of the rat. The PRL isoform profile was assessed in homogenates of
      pituitaries and in short-term incubation media. Comparisons between homogenates,
      which always contained isoforms 1, 2, 3, and 3' (numbered according to increasing
      acidity), and media showed nonproportional release of the isoforms at all stages.
      Of great interest were the release of isoform 1 (a nonphosphorylated form) only
      at estrus and the lack of release of isoform 3' (a phosphorylated form) only in
      the afternoon of proestrus. This lack of release of 3' was accompanied by a
      marked increase in the release of isoform 2 (the unmodified polypeptide). These
      results suggest a unique function for isoform 1 during estrus and a role for
      increased isoform 2 and absent isoform 3' during the proestrus surge of PRL.
      Moreover, they suggest that fluctuations in the biological activity and
      immunoreactivity of serum PRL during the estrous cycle could be due, at least in
      part, to fluctuations in the isoform profile.

PMID- 8264863
TI  - Presence and differential distribution of distinct forms of immunoreactive
      gonadotropin-releasing hormone in the musk shrew brain.
AB  - Gonadotropin-releasing hormone (GnRH) immunoreactive cells and fibers were
      revealed in olfactory regions, the ventral forebrain, and in the midbrain of the
      musk shrew (Suncus murinus). Immunoreactive neurons in olfactory and
      telencephalic areas were specific for the mammalian form of GnRH. Cell bodies in
      the midbrain, however, cross-reacted with an antibody specific for chicken-II
      GnRH. High-performance liquid chromatography and radioimmunoassay analyses
      confirmed these results; high levels of chicken II GnRH were present in the
      midbrain, and mammalian GnRH was detected in both forebrain and midbrain. In
      addition, a third, late-eluting form of GnRH was revealed using high-performance
      liquid chromatography in both forebrain and midbrain of the musk shrew. Midbrain
      neurons containing GnRH have not been reported previously in a mammal, although
      mesencephalic GnRH immunoreactivity within cell bodies is common among
      nonmammalian vertebrates. Likewise, while multiple forms of GnRH have been
      reported in nonmammalian vertebrates and several metatherian species of mammals,
      this is the first report on multiple forms of GnRH in the brain of a placental
      mammal. Taken together, the findings suggest that this primitive eutherian mammal
      has retained the ability to produce GnRH protein in the midbrain. This feature of
      the GnRH system has been conserved among nonmammalian vertebrates, but appears to
      have been lost in modern placental mammal species. The functional significance of
      this group of neurons has yet to be determined.

PMID- 8264864
TI  - Alpha-melanocyte-stimulating hormone abolishes IL-1- and IL-6-induced
      corticotropin-releasing factor release from the hypothalamus in vitro.
AB  - Alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone
      (ACTH), peptides derived from the precursor proopiomelanocortin, share amino acid
      homology at the aminoterminus of ACTH, occur within the pituitary and the brain
      and are potent antipyretic compounds in cytokine-mediated fever. Because alpha
      MSH and ACTH act within the hypothalamus to block leukocytic pyrogen- or cytokine
      mediated fever, we hypothesized that these compounds might also be capable of
      blocking the action of interleukin-1 (IL-1) and interleukin-6 (IL-6) to stimulate
      corticotropin-releasing factor (CRF) release from the hypothalamus. Mediobasal
      hypothalami (MBH) were incubated in vitro. After 60 min preincubation in Krebs
      Ringer bicarbonate buffer (KRB), MBH explants were incubated for 30 min with KRB
      alone or KRB containing IL-6 (10(-13) M), IL-1 (10(-16)-10(-10) M) and/or ACTH1
      24 (10(-15)-10(-9) M) or alpha-MSH (10(-15)-10(-8) M); CRF release into the
      incubation medium was measured by RIA. None of the ACTH1-24 or alpha-MSH
      concentrations changed basal CRF release significantly. As we reported
      previously, IL-6 (10(-13) M) increased CRF release; this increase was suppressed,
      in a dose-dependent fashion, by alpha-MSH at concentrations of 10(-13)-10(-11) M,
      with the maximal inhibitory effect observed at 10(-13) M. ACTH1-24 also exerted a
      dose-dependent inhibitory effect on IL-6-stimulated CRF release but at even lower
      concentrations (10(-15)-10(-13) M) with the maximal inhibitory effect observed
      with the 10(-14) M concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264865
TI  - Stress-induced norepinephrine release in the paraventricular nucleus of rats with
      brainstem hemisections: a microdialysis study.
AB  - Immobilization (IMMO) of conscious rats evokes marked increases in release of
      norepinephrine (NE) in the paraventricular nucleus (PVN) of the hypothalamus,
      consistent with a role of NE in the PVN release of corticotropin-releasing
      hormone and therefore in pituitary-adrenocortical activation during stress. The
      present study examined the effects of surgical hemisection of the brainstem
      between the locus ceruleus and rostral portion of the medulla on release of NE in
      the PVN of the hypothalamus in vivo in conscious rats, at baseline and during
      IMMO. Concentrations of NE, the intraneuronal NE metabolite dihydroxyphenylglycol
      (DHPG), and the dopamine metabolite dihydroxyphenylacetic acid (DOPAC) were
      measured in microdialysate samples obtained beginning 24 h after implantation of
      a microdialysis probe in the PVN either ipsilateral or contralateral to the
      hemisection. On the lesioned side, baseline levels of NE, DHPG, and DOPAC were
      significantly lower and IMMO-induced increases were smaller than in sham-operated
      rats. Contralateral to the hemisection, DOPAC levels were significantly reduced.
      Neither baseline levels nor IMMO-induced increases in plasma corticosterone
      levels differed between lesioned and sham-operated animals. The present results
      indicate that: (1) NE release in the PVN at baseline and during IMMO depends
      mainly on ascending medullary tracts from ipsilateral brainstem A1 and A2
      catecholaminergic areas, with small contributions from the locus ceruleus and
      from contralateral medullary cells, and (2) brainstem hemisection does not
      influence IMMO-induced activation of the hypothalamic-pituitary-adrenocortical
      axis as indicated by plasma corticosterone levels in conscious rats.

PMID- 8264866
TI  - Hypothalamic involvement in the activation of the pituitary-adrenocortical axis
      by nerve growth factor.
AB  - Intravenous injection of nerve growth factor (NGF) into rats produces a dose
      dependent (from 0.1 to 5 nmol/kg) increase in circulating concentrations of
      adrenocorticotropin (ACTH) and corticosterone. We have investigated whether this
      effect is produced through a direct action on a component of the hypothalamo
      pituitary-adrenocortical axis. NGF (50 and 500 nM), added to the incubation
      medium of in vitro isolated pituitary segments or dispersed adrenal cells, did
      not modify either basal and stimulated release of biologically active or
      immunoreactive ACTH or release of corticosterone, respectively. The presence of
      NGF in the incubation medium of in vitro isolated hypothalami produced a dose
      dependent (from 150 to 600 nM) increase of both release and content of some
      material with corticotropin-releasing bioactivity. The nature of this
      corticotropin-releasing bioactivity was determined directly by radioimmunoassays.
      Results have indicated that NGF induced an increase of both release and content
      of hypothalamic arginine-vasopressin (AVP), while no changes were observed in the
      release and content of hypothalamic corticotropin-releasing hormone (CRH). These
      results suggest that adrenocortical stimulation by NGF in vivo could be mediated
      by the release of hypothalamic AVP rather than CRH. The finding that in vivo NGF
      stimulatory effect was not abolished by the specific CRH antagonist alpha-helical
      CRH(9-41), while it was accompanied by an increase in circulating AVP levels,
      supports this interpretation. However, the fact that the hypothalamus is
      stimulated in vitro by NGF concentrations higher than those expected to reach
      this structure after systemic injection of active doses raises the possibility
      that other brain areas such as the hippocampus participate in NGF-induced
      adrenocortical activation.

PMID- 8264867
TI  - Passive immunization and hypothalamic peptide secretion.
AB  - Passive immunization is a common approach used to eliminate the biological
      activity of an endogenous substance by its binding to a specific antibody (Ab).
      Surprisingly little information has been gathered on the mechanisms involved.
      Moreover, the possibility that immunoneutralization could affect also the
      secretion of the antigen itself has been mostly ignored. To study hypothalamic
      neuropeptide secretion under the condition of passive immunization, labeled and
      unlabeled monoclonal antibody (MoAb) against arginine vasopressin (AVP) was
      injected intravenously. After 2 h a similar amount of 125I-MoAb was found in
      hypophyseal portal and peripheral (femoral artery) plasma, showing a distribution
      volume of 73.2 ml/kg. Assessment of the MoAb dilution in the same plasma samples
      from the binding studies revealed substantially higher dilutions (800-5,700
      ml/kg). Such a MoAb dilution (saturation) would be attained by the binding of 130
      290 pmol AVP/ml plasma. The calculated amount of plasma AVP decreased by one half
      within the interval from 2 to 24 h after Ab injection, similarly as did the 125I
      MoAb content. Intravenous injection of polyclonal corticotropin-releasing hormone
      (CRH) Ab resulted in a decrease of plasma adrenocorticotropin and corticosterone
      levels. After 24 h the dilution of the Ab in portal plasma exceeded two times
      that in peripheral plasma. CRH concentrations of 0.6-2.5 pmol/ml were found by
      specific radioimmunoassay after its dissociation from the Ab in plasma. The CRH
      concentration was higher in portal than in peripheral plasma and was related to
      the amount of the Ab injected. CRH mRNA levels in the paraventricular nucleus
      were significantly increased in CRH Ab as compared with normal rabbit serum
      injected rats.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264868
TI  - Interaction of oestradiol, alpha-melanotrophin and noradrenaline within the
      ventromedial nucleus in the control of female sexual behaviour.
AB  - A possible inter-relationship between oestrogen, alpha-melanotrophin (alpha MSH)
      and NA in the ventromedial nucleus (VMN) has been studied in ovariectomised
      adrenalectomised rats primed with a low dose of oestradiol benzoate (2 or 5
      micrograms OB), which induces receptivity in approximately half the rats. Priming
      with OB increased NA turnover in the VMN (as assessed by the decline in NA
      concentration 1 h after 250 mg/kg alpha-methyl tyrosine alpha MT) and also
      enhanced the release of NA from basal medial hypothalamic fragments in vitro.
      This occurred whether the rats were receptive or non-receptive. Injection of 20
      micrograms/rat alpha MSH, 4 h before autopsy in OB-primed rats, reduced NA
      turnover in the VMN but only in the receptive animals. alpha MSH had no effect on
      NA content in the VMN, but prevented the decline normally induced by the alpha
      MT, indicating an inhibition of release. Application of 1 microgram/ml alpha MSH
      to incubated hypothalamic fragments enhanced release of NA in the tissue obtained
      from untreated controls and the OB-non-receptive group, but had no effect on the
      tissue of the OB-receptive animals. Perhaps NA release had already occurred in
      vivo in the latter group. alpha MSH (100 ng/side/rat) and NA (20, 200 and 2,000
      ng/side/rat) were injected into the VMN of ovariectomised-adrenalectomised rats
      primed with 1 microgram OB. Both agents stimulated lordosis in non-receptive
      animals with a peak activity at 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264869
TI  - Alpha-melanocyte-stimulating hormone is present in the inferior petrosal sinuses
      in patients with Cushing's disease.
AB  - Plasma ACTH, beta-endorphin and alpha-melanocyte-stimulating hormone levels were
      evaluated in the inferior petrosal sinuses and in the periphery of 22 patients
      affected by Cushing's disease, 11 patients with other pituitary diseases
      subjected to simultaneous and bilateral inferior petrosal sinus sampling and in
      the peripheral blood of 15 normal subjects. In patients with Cushing's disease
      ACTH, beta-endorphin and alpha-melanocyte-stimulating hormone levels in the
      inferior petrosal sinus ipsilateral to the adenoma were significantly higher than
      in the periphery and in the contralateral inferior petrosal sinus (p < 0.01, p <
      0.01 and p < 0.05, respectively). In patients with other pituitary diseases only
      ACTH and beta-endorphin, but not alpha-melanocyte-stimulating hormone levels in
      both inferior petrosal sinuses were significantly higher than in the periphery (p
      < 0.01). Furthermore, no difference was found in the peripheral blood among
      patients with Cushing's disease, patients with other pituitary diseases and
      normal subjects for ACTH and beta-endorphin level. By contrast, in patients with
      Cushing's disease peripheral alpha-melanocyte-stimulating hormone levels were
      significantly higher than in patients with other pituitary diseases and in normal
      subjects (p < 0.05). In conclusion, the results of the present study suggest that
      only in patients with Cushing's disease, but not in patients with other pituitary
      diseases, alpha-melanocyte-stimulating hormone is released by adenomatous
      pituitary corticotrophs together with ACTH and beta-endorphin.

PMID- 8264870
TI  - Preferential distribution of C-terminal fragments of [hydroxyproline9]LHRH in the
      rat hippocampus and olfactory bulb.
AB  - Several molecular forms related to the decapeptide LHRH were characterized and
      quantified in various brain structures of intact and castrated male and female
      rats. Distinct moieties were separated by high performance liquid chromatography
      (HPLC) and radioimmunoassayed against anti-LHRH antibodies of different
      specificities. The hypothalamus contained the highest concentration of LHRH-like
      material detected by the antisera. The predominant (89%) molecular form recovered
      from that structure was LHRH itself; 9% of the material corresponded to
      [hydroxyproline9]LHRH ([Hyp9]LHRH), an endogenous posttranslational product of
      the LHRH precursor, and the residual immunoreactivity was accounted for by C
      terminal fragments of both decapeptides, as assessed after labelling HPLC columns
      with appropriate synthetic or endogenous hypothalamic peptides. The proportions
      were the same in both sexes and were not affected by castration, in spite of a
      lesser overall LHRH activity in females and in castrates. LHRH and [Hyp9]LHRH
      were also detected in the olfactory bulb and the hippocampus. In these structures
      however, most (97%) LHRH-related molecules corresponded to C-fragments derived
      from [Hyp9]LHRH, whereas only very few fragments derived from the nonhydroxylated
      decapeptide were found. Sex or castration affected neither total nor relative
      concentrations of LHRH-derived molecules in the olfactory bulb and the
      hippocampus. Taken altogether, these observations are suggestive of a different
      LHRH metabolic regulation in neurons projecting to either the median eminence or
      extrahypothalamic areas. In the latter case, larger amounts of the LHRH precursor
      appear processed to [Hyp9]LHRH. Recovery of relatively high concentrations of
      [Hyp9]LHRH C-fragments in the olfactory bulb and the hippocampus reflects the
      higher resistance of the Hyp9-Gly10-NH2 than the Pro9-Gly10-NH2 peptide bond to
      hydrolysis by the postproline cleaving enzyme. In view of reports that
      intracerebral administration of C-terminal fragments of LHRH are able to trigger
      sex behavior, our finding that extrahypothalamic structures contain relatively
      high concentrations of the [Hyp9]LHRH-derived, more stable C-fragments suggests
      that these catabolites may have a role in the regulation of sex behavior.

PMID- 8264872
TI  - Isotonic but not hypertonic ethanol stimulates LHRH secretion from perifused rat
      median eminence.
AB  - We utilized luteinizing hormone-releasing hormone (LHRH) secretion by perifused
      minced rat hypothalamic median eminence (ME) tissue to evaluate whether isotonic
      ethanol would stimulate neurosecretion as it does secretion from pituitary cells.
      Isotonic ethanol induced a dose-dependent burst of LHRH secretion which was
      maximal at 2-3 min and returned to near baseline by 10 min. In Ca(2+)-depleted
      media (< 2 microM Ca2+), stimulation of secretion by isotonic ethanol was
      enhanced, but secretion induced by depolarizing 30 mM K+ was abolished.
      Hypertonic ethanol was ineffective in stimulating LHRH secretion in either normal
      or Ca(2+)-free media. The secretory response of hypothalamic LHRH-secreting cells
      to ethanol and its negative modulation by medium Ca2+ is thus identical to that
      of normal anterior pituitary cells and presumably is caused by cell swelling
      resulting from influx of permeant ethanol molecules across the plasmalemma.

PMID- 8264871
TI  - GnRH-associated peptide decreases cyclic AMP accumulation in the GH3 pituitary
      cell line.
AB  - We have studied the effects of GnRH-associated peptide (GAP) on cAMP, cGMP
      production and intracellular calcium (Ca2+) levels in the clonal rat GH3
      pituitary cell line. We show that GAP decreases cAMP production in a dose
      dependent manner. A 20-min incubation with GAP at concentrations greater than 0.1
      nM resulted in a significant decrease in cAMP production. 100 nM GAP decreased
      cAMP production to 65% of that in control. The kinetics of the GAP effect were
      also studied. We show that cAMP levels fall to 68% of control levels within 2 min
      following administration of 10 nM GAP. Maximal inhibition was obtained after 3
      min. The effect was only transient since GAP had no significant residual effect
      after 40 min. Conversely, up to 100 nM GAP failed to affect cGMP levels. We have
      also studied the effect of GAP on [Ca2+]i levels and showed that GAP decreases
      [Ca2+]i by inhibiting Ca2+ transients. GAP also reduced VIP-stimulated cAMP
      production and inhibited Ca2+ transients induced by VIP. The effect of GAP on
      cAMP production and Ca2+ transients was abolished by pertussis toxin treatment.
      These observations are consistent with GAP inhibiting PRL secretion through a
      cAMP, Ca(2+)-dependent process.

PMID- 8264873
TI  - Chronobiology of prolactin secretion in women: diurnal and sleep-related
      variations in the pituitary lactotroph sensitivity.
AB  - While a nocturnal rise accounts for the marked circadian variability of prolactin
      (PRL) secretion in humans, the mechanisms subserving this neuroendocrine
      manifestation are still obscure. Since gonadotropin-releasing hormone (GnRH)
      stimulates PRL under physiological conditions, we questioned whether changes in
      the pituitary lactotroph sensitivity to GnRH during the 24-hour cycle may
      contribute to the expression of circadian PRL rhythmicity. Accordingly, 8 women
      were studied in the early follicular phase of their cycles (days 2-5) on 6
      occasions in random order: during daytime between 10.00 and 14.00 h ('day'
      studies), at night between 22.00 and 02.00 h, when the women were awake ('night'
      studies), and finally, during the identical night hours, when the women were
      asleep ('sleep' studies). On all occasions, blood was collected at 10-min
      intervals for 4 h, while either GnRH (25 micrograms i.v. bolus) or saline (as
      control) was injected twice within 2 h. As assessed by the net PRL increments
      (differences between unstimulated nadir and stimulated peak) and the areas under
      the PRL response curves, the PRL secretion was not substantially altered
      following GnRH stimulations during the day studies. In contrast, PRL release was
      markedly enhanced (p < 0.05 or less vs. day studies), when GnRH was administered
      during the night studies. This GnRH-stimulated PRL release was even further
      increased (p < 0.01 vs. day, p < 0.05 vs. night or saline studies), when GnRH had
      been given during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264874
TI  - Familial subarachnoid hemorrhage in east Finland, 1977-1990.
AB  - The familial occurrence of cerebral aneurysms in a defined clinical group of 1150
      patients from a defined catchment area was studied. Two or more proven aneurysmal
      subarachnoid hemorrhage (SAH) patients within the same family were included. Of
      these 1150 patients, 113 (10%) had a proven familial occurrence of aneurysmal
      SAH. These 113 patients form 91 SAH families with a total of 203 aneurysm
      patients. Fifty-four percent of the patients were female, and the mean age in
      female patients was 49 years and in male patients was 44 years. In 23% of the
      families, three or more members were identified as having cerebral aneurysms.
      Middle cerebral artery aneurysms were the most common type (47%). Based on the
      high incidence (10%) of familial intracranial aneurysms among SAH patients, a
      prospective study of healthy family members for incidental intracranial aneurysms
      was performed, with positive findings of 12%.

PMID- 8264875
TI  - Aneurysmal rupture during angiography.
AB  - The aim of the present study was to analyze the clinical data on rebleeding in
      cerebral aneurysms during angiography and to evaluate the importance of the time
      interval between the latest rupture and angiography. Fourteen personal cases and
      202 patients reported in the literature are reviewed. Rebleeding during
      angiography occurred most often (78%) on Day O; 89% bled when angiography was
      performed within 6 hours of the latest rupture. The prognosis in such ruptures
      was poor, with a mortality of 79%. Intentional delay in angiography of at least 6
      hours from the latest rupture is recommended if the associated hematoma is not
      large.

PMID- 8264876
TI  - Endarterectomy of the intradural vertebral artery via the far lateral approach.
AB  - Transient ischemic attacks (TIAs) of the posterior circulation are associated
      with a significant risk of subsequent infarction, particularly when caused by
      stenotic lesions in the intracranial portion of the vertebral artery (VA). Eight
      patients who had persistent posterior circulation TIAs despite receiving maximal
      medical therapy (including anticoagulation) and who had angiographic evidence of
      severe stenosis of the proximal intracranial VA with poor collateral flow were
      treated by endarterectomy of the intradural VA. Their ages ranged from 52 to 65
      years. Five of these operations were performed via the far lateral approach. In
      all patients, the contralateral VA was hypoplastic or occluded, or ended in the
      posterior inferior cerebellar artery. Postoperative angiograms showed that the
      arteries of five of the patients were widely patent, one was improved but still
      stenotic, and two were occluded. The latter two patients subsequently underwent
      thrombectomy, after which the artery was patent in one patient and remained
      occluded in the other. After surgery, the TIAs of seven patients were relieved
      completely, and the patients were neurologically intact. The patient with
      persistent occlusion ultimately had moderate disability. Complications included
      the two cases of thrombotic occlusion that required a second operation, three
      cases of communicating hydrocephalus that required lumboperitoneal shunts, and
      two cases of transient dysfunction of the 9th and 10th cranial nerves. Suitable
      patients with persistent posterior circulation TIAs refractory to medical therapy
      who have appropriate angiographic evidence of proximal VA stenosis and poor
      collateral flow may benefit from endarterectomy of the intradural VA.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8264877
TI  - Endovascular treatment of external carotid-jugular fistulae in the parotid
      region.
AB  - A series of eight patients with large arteriovenous fistulae involving the
      external carotid artery and the jugular vein that were treated with the
      endovascular technique are reviewed. The origin of the fistula was congenital in
      six patients, spontaneous in one, and iatrogenic in one. All the fistulae were
      located in the parotid region, and single channel arteriovenous shunts were
      evident in all the cases. Endovascular treatment was performed with a detachable
      balloon. All the patients were cured, and no complications were observed. No
      recurrences were observed after a clinical follow-up of 6 months to 12 years
      (mean, 5 yr). Endovascular treatment offers the advantage of being less traumatic
      because it avoids facial scars and injury to the facial nerve. This is especially
      important in children, who most commonly have this condition. In our group,
      endovascular treatment is considered first in the management of external carotid
      jugular fistulae.

PMID- 8264878
TI  - Ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2
      chloroethyl)-1-nitrosou rea hydrochloride.
AB  - We report on the toxicity, intrathecal pharmacokinetics, and therapeutic effect
      of the ventriculolumbar perfusion of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1
      (2-chloroethyl)-1-nitros our ea hydrochloride (ACNU) against the subarachnoid
      dissemination of primary central nervous system tumors. Fifteen patients received
      ventriculolumbar perfusion of ACNU. One was treated with ventriculolumbar
      perfusion of ACNU alone, and the others underwent concomitant systemic
      chemotherapy; three of these patients received irradiation as well. ACNU was
      administered at an initial dose of 0.5 and was increased to 1.5 to 10.0 mg in six
      patients. Because of a lack of Level 2 or greater toxicity, the subsequent seven
      patients received 8.7 to 10.0 mg of ACNU dissolved in artificial cerebrospinal
      fluid (CSF) at a concentration of 0.1 mg/ml, from the start of the treatment.
      During ACNU administration, the lumbar CSF was drained at approximately the same
      rate as that of the infusion. Twelve patients received from 3 to 42 courses
      (average, 14 courses). The cumulative dose of ACNU ranged from 5 to 330.4 mg
      (average, 82.9 mg). One patient had a convulsion; two patients experienced
      transient headache, nausea, and vomiting; two others reported transient headache,
      nausea, vomiting, and fecal incontinence; and one experienced transient nausea,
      vomiting, and fecal incontinence. No side effects were noted in the other nine
      patients. When 9.0 to 9.5 mg of ACNU, dissolved in 90 to 95 ml of artificial CSF,
      was administered for 37 to 52 min, the maximum concentration of ACNU in the
      lumbar CSF was 9.86 to 12.79 micrograms/ml and the area under the drug
      concentration-time curve was 260.8 to 502.5 micrograms.min/ml.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8264879
TI  - Management of unilateral locked facet of the cervical spine.
AB  - Twenty-four patients with unilateral cervical locked facets were treated between
      1986 and 1990. The primary mechanisms of injury were vehicular accidents (58%)
      and altercations (38%). The level of unilateral facet dislocation was C5-C6
      (41%), C6-C7 (25%), C3-C4 (17%), and C4-C5 (17%). Seventeen (70%) came to the
      hospital with radiculopathy, five (20%) were normal, and two (10%) had spinal
      cord injuries. Plain films showed subluxation but no fracture. All patients had a
      cervical computed tomographic scan. Fracture in addition to facet locking was
      seen in 12 (50%) of 24 scans: 5 with facet fracture, 4 with facet/laminar
      fractures, 2 with facet/laminar/body fractures, and 1 foramen transversarium
      fracture. On the basis of CT findings, closed reduction was thought to be
      contraindicated in two cases. Five patients (22%) underwent successful closed
      reductions. Two of the patients with closed reductions were placed in a halo but
      again had subluxation. Thus, 24 patients underwent surgery for open reduction,
      posterior spinous process wire fixation, and facet wiring to struts of the iliac
      crest for bony fusion. The initial surgery was successful in 23 (96%) of 24
      patients. One patient experienced subluxation and underwent further surgery for
      anterior cervical fusion/plating. Two wound infections were treated, and there
      were no deaths or neurological worsening. At 1 year, all deficits had improved.
      Of 16 radiculopathies, 3 (19%) had persistent 4/5 weakness, and the rest were
      normal, including 2 delayed-diagnosis patients who both showed improvement from
      2/5 to 5/5 strength within 1 week of surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8264881
TI  - Foramen magnum decompression with removal of the outer layer of the dura as
      treatment for syringomyelia occurring with Chiari I malformation.
AB  - The surgical results of foramen magnum decompression in seven patients with
      syringomyelia associated with Chiari I malformations are reported. The patients
      were two men and five women, ranging in age from 23 to 54 years (mean, 30 yr). A
      bony foramen magnum decompression combined with the removal of the outer layer of
      the dura mater was performed in seven patients. In an average postoperative
      follow-up period of 2 years (range, 1-3 yr), neurological symptoms and signs
      improved in six of seven patients and were unchanged in one patient.
      Postoperative magnetic resonance imaging scans taken a few weeks after surgery
      showed a decrease in the size of the syrinx or a disappearance of the syrinx in
      five of seven patients; a few months were required for a similar reduction in the
      remaining two patients. In all seven patients, the decompression of the foramen
      magnum proved to be sufficient, as disclosed by postoperative magnetic resonance
      imaging. Foramen magnum decompression by our surgical technique is advantageous
      because all the procedures are extradural and there are, therefore, fewer
      postoperative complications than the foramen magnum decompression techniques
      previously reported. Foramen magnum decompression by the authors' surgical
      technique is effective as the initial surgical treatment for syringomyelia
      associated with Chiari I malformations.

PMID- 8264880
TI  - Brucellosis of the spine.
AB  - The spinal form of brucellosis is still a disabling disease in many countries
      outside North America and northern and central Europe. Fifteen consecutive cases
      of spinal brucellosis diagnosed and treated over a 20-year period were reviewed
      retrospectively. Six patients were farmers, while 10 patients had a history of
      ingestion of unpasteurized milk or other dairy products. A high index of
      suspicion is necessary for the diagnosis, since there are no pathognomonic signs
      or symptoms. Radiological assessment of the disease was reviewed and highlights
      in the differential diagnoses were stressed. The diagnosis was based on actual
      culture of Brucella bacilli in seven patients. The principal treatment of
      brucellosis of the spine is conservative, namely, immobilization and
      antimicrobial therapy. We have found both a combination of ofloxacin and rifampin
      and ofloxacin monotherapy efficient as the early regimens used in this series.
      Three patients had to undergo surgery, since a diagnosis could not be made in any
      other way.

PMID- 8264882
TI  - Selective dorsal rhizotomy: outcome and complications in treating spastic
      cerebral palsy.
AB  - Selective dorsal rhizotomy has shown great promise as a treatment for the
      functional disabilities and deforming hypertonia of spastic cerebral palsy. At
      New York University Medical Center, 200 children underwent this procedure between
      1986 and 1990. All groups, whether walkers, crawlers, or nonlocomotors, showed
      improvement in the tone and range of most muscles tested. Half of these patients
      experienced complications. Thirty-five of these were serious and included
      bronchospasm (5.5%), aspiration pneumonia (3.5%), urinary retention (7%), and
      sensory loss (2%). There are, however, clear indications that warn of these
      complications; monitoring and prophylactic treatment can minimize their effects,
      and the possibility of such problems is more than offset by the proven benefits
      of this operative procedure.

PMID- 8264883
TI  - Ventriculoperitoneal shunt infections with gram-negative bacteria.
AB  - Infection causes major morbidity and mortality in patients with cerebrospinal
      fluid (CSF) shunts. The prognosis of CSF shunt infections caused by Gram-negative
      bacteria (GNB) has been thought to be particularly poor. The authors reviewed all
      GNB shunt infections treated at Children's Memorial Hospital from January 1986 to
      January 1990 (n = 23). Of these infections 20 (87%) occurred within 4 weeks after
      shunt revision (median, 10 days). The most frequent symptoms were fever,
      lethargy, and irritability; the illness was not severe in the majority of these
      patients. Escherichia coli was isolated from 12 of 23 patients (52%), Klebsiella
      pneumoniae from 5 (22%), and mixed GNB from 3 (13%) patients. Initial treatment
      always included immediate shunt removal, externalized ventricular drainage, and
      intravenous antibiotics. Extraventricular drainage revision and/or
      intraventricular antibiotics were required in four patients whose CSF cultures
      were persistently positive for GNB. At admission, these patients had CSF glucose
      levels of < 10 mg/dl and CSF positive for GNB by Gram's stain. The overall cure
      rate was 100%, and no recurrence was observed; however, a subsequent infection
      with a different organism developed in four patients. Only 2 of 19 patients (11%)
      who were followed up suffered apparent CNS damage. One patient died of unrelated
      causes shortly after treatment. Our findings indicate that 1) patients with GNB
      CSF shunt infections often appear relatively well at presentation; 2) CSF
      positive for GNB by Gram's stain and very low CSF glucose levels predict
      continued positive CSF cultures, despite appropriate antibiotic therapy; and 3)
      GNB CSF shunt infections can be successfully treated by prompt shunt removal,
      extraventricular drainage, and intravenous antibiotics.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8264884
TI  - Ischemic lesions in basal ganglia in children after minor head injury.
AB  - Twenty-three children under the age of 6 1/2 years developed immediate unilateral
      weakness after an apparently minor head injury. Computed tomography disclosed a
      hypodense lesion in the basal ganglia. The lesion appeared to be caused by an
      infarct in the basal ganglia. All but one of the children recovered completely
      within 4 months.

PMID- 8264885
TI  - An evaluation of the camino ventricular bolt system in clinical practice.
AB  - The camino ventricular bolt system has been used to monitor intracranial pressure
      in patients after severe head injury. The correlation between the ventricular
      pressure measured with the Camino device and an external transducer showed that
      the Camino accurately measured intracranial pressure over a wide range, but that
      it read an average of 1.15 mm Hg higher than that obtained by the external
      transducer. The technique has the advantage over a remote transducer because it
      is sited within the ventricle. This may be of value in wave-form analysis.

PMID- 8264886
TI  - Role of cranial bone mobility in cranial compliance.
AB  - Increases in intracranial pressure are normally buffered by the displacement of
      blood and cerebrospinal fluid from the cranium when there is an increase in
      intracranial volume (ICV). How much pressure increases with an increase in ICV is
      expressed in the calculation of cranial compliance (delta ICV/delta P, where
      delta P is change in pressure) and elastance (delta P/delta ICV). Data reported
      here indicate that the movement of the cranial bones at their sutures is an
      additional factor defining total cranial compliance. Using controlled bolus
      injections of artificial cerebrospinal fluid into a lateral cerebral ventricle in
      anesthetized cats and a newly developed instrument to quantify cranial bone
      movement at the midline sagittal suture where the bilateral parietal bones meet,
      we show that these cranial bones move in association with increases in ICV along
      with corresponding peak intracranial pressures and changes in intracranial
      pressure. External restraints to the head restrict these movements and reduce the
      compliance characteristics of the cranium. We propose that total cranial
      compliance depends on the mobility of intracranial fluid volumes of blood and
      cerebrospinal fluid when there is an increase in ICV, but it also varies as a
      function of cranial compliance attributable to the movement of the cranial bones
      at their sutures. Our data indicate that although the cranial bones move apart
      even with small (nominally 0.2 ml) increases in ICV, total cranial compliance
      depends more on fluid migration from the cranium when ICV increases are less than
      approximately 3% of total cranial volume. Cranial bone mobility plays a
      progressively larger role in total cranial compliance with larger ICV increases.

PMID- 8264887
TI  - Rapid detection of transferrin receptor expression on glioma cell lines by using
      magnetic microspheres.
AB  - A rapid method for detecting the presence of transferrin receptors (TR) on human
      glioblastoma-derived cell lines is presented. The development of new treatment
      modalities, such as immunotoxins for central nervous system cancer, requires the
      identification of appropriate surface antigens on tumor cells. Seven established
      human glioblastoma-derived cell lines were assayed for the presence of TR with
      antibody-coated magnetic microspheres (immunobeads). The immunobeads bound to
      glioblastoma cells in the presence of human anti-TR monoclonal antibodies to a
      significantly greater degree than to control cell lines (P < 0.0001). The
      expression of TR was confirmed by standard immunocytochemical techniques. A 9L
      rat gliosarcoma cell line was used as a nonhuman control and did not demonstrate
      TR expression by either the immunobead assay or immunocytochemistry. This assay
      represents a simple, sensitive way to detect TR expression on malignant cells,
      which may be useful for the identification of other cell surface antigens that
      can be exploited by targeted therapies.

PMID- 8264888
TI  - Difluoromethylornithine decreases postischemic brain edema and blood-brain
      barrier breakdown.
AB  - Brain polyamines have been associated with posttraumatic vasogenic edema and
      blood-brain barrier (BBB) breakdown seen in some models of brain injury. We
      hypothesized that the inhibition of the enzyme responsible for polyamine
      production with the decarboxylase difluoromethylornithine (DFMO) may decrease BBB
      breakdown after a focal brain ischemic stroke. Thirty-two cats underwent 8 hours
      of middle cerebral artery occlusion and one of four treatments: sham operation
      (Sham), ischemia (Isc), ischemia/DFMO (Isc/DF), and ischemia/DFMO/putrescine
      (Isc/DF/PU). The regional brain specific gravity and the volume of Evans blue
      (EB) extravasation were measured at the time of death. The groups were monitored
      for temperature, heart rate, blood pressure, and arterial blood gases, and the
      values did not differ outside normal physiological ranges. EB results were
      expressed as the percentage of the hemisphere stained and showed the following:
      Sham, 2.23%; Isc, 32.8%; Isc/DF, 5.6%; Isc/DF/PU, 36.3%. As a measure of BBB,
      ischemia increased EB staining; DFMO pretreatment decreased the amount of EB
      staining to control levels; and the polyamine putrescine abolished the protective
      effect of DFMO (all significant at P = 0.05). DFMO pretreatment also resulted in
      a significant (P = 0.05) return to control values for specific gravity in the EB
      stained regions (1.0328) of ischemic animals. This effect was present primarily
      in the white matter. Treatment with DFMO, an ornithine decarboxylase inhibitor,
      significantly decreased postischemic BBB breakdown and vasogenic edema in this
      model.

PMID- 8264889
TI  - Cerebral phaeohyphomycosis.
AB  - A 14-year-old girl with a rare form of fungal brain abscess involving the dura
      and brain parenchyma is reported. No portal of entry of the infection was found.
      Histological findings and fungal culture both indicated that the causative agent
      was Xylohypha bantiana, an uncommon dematiaceous fungus. A review of the
      literature suggests that this infection, which affects primarily young male
      patients, exhibits distinct neurotropism. Despite therapy, the prognosis is
      generally poor.

PMID- 8264890
TI  - Intracerebral hematoma related to thrombolysis for myocardial infarction.
AB  - The incidence of intracerebral hematomas after myocardial infarction increases
      after thrombolysis. As noted in the case described, clots formed after the
      administration of thrombolytic agents may remain liquid, and this blood can be
      drained by a catheter. However, in this case, the patient continued to bleed
      locally. This problem requires the development of methods to stop such ongoing
      local bleeding. It may be prevented in the future by improved thrombolytic drugs.

PMID- 8264891
TI  - Successful treatment of recurrent malignant germ cell tumors: report of two
      cases.
AB  - We report two patients with recurrent malignant germ cell tumors who were
      successfully treated with radiation therapy and cisplatin combination
      chemotherapy. Patient 1, who had a suprasellar mixed yolk sac tumor, had been
      free of tumor for 3.5 years after cisplatin/vinblastine/bleomycin combination
      chemotherapy alone but showed a recurrent tumor in the pineal region. In Patient
      2, who had a pineal alpha-fetoprotein-producing tumor, recurrent tumors appeared
      in the lateral ventricle 3 years after the tumor was controlled by radiation and
      cisplatin/vinblastine/bleomycin therapy. They were treated successfully again by
      radiation therapy, followed by cisplatin and etoposide combination therapy, and
      they have been free of tumor for 5.5 and 7 years after recurrence, respectively.
      The total dose of cisplatin in both patients exceeded 1,000 mg/m2, which would
      have contributed to the control of the recurrent tumors. Anterior pituitary
      dysfunction observed in Patient 1 did not improve, even after tumor disappearance
      by chemotherapy, suggesting severe damage to the neurohypophysis by direct
      invasion of the tumor.

PMID- 8264892
TI  - Prepubescent pituitary null cell macroadenoma with silent macroscopic apoplexy:
      case report.
AB  - Secreting pituitary adenomas have marked prevalence in pediatric adenomas. We
      described a case of an 11-year-old boy with pituitary null cell macroadenoma with
      silent macroscopic pituitary apoplexy. The patient was admitted with bitemporal
      hemianopsia and a gradual deterioration of visual acuity. An endocrinological
      study revealed a low concentration of testosterone and in the plasma a decreased
      response of luteinizing hormone and follicle-stimulating hormone to luteinizing
      hormone-releasing hormone. This patient may be the first case of prepubescent
      null cell macroadenoma confirmed with immunohistochemical study in addition to
      the findings of classical histopathology.

PMID- 8264893
TI  - Deep cerebral venous system thrombosis: case report.
AB  - A 38-year-old woman with thrombosis of the deep cerebral venous system, presumed
      to be secondary to the use of the oral contraceptive pill, is reported. The use
      of cerebral angiography and magnetic resonance imaging in establishing the
      diagnosis and management strategies is discussed. It is concluded that magnetic
      resonance imaging is an appropriate investigative modality for diagnosis and
      therapeutic decision making, and that, as with superficial cerebral dural sinus
      and venous thrombosis, anticoagulation is a safe and effective therapy.

PMID- 8264894
TI  - Progressive myelopathy caused by intracranial dural arteriovenous fistula: report
      of two cases and review of the literature.
AB  - We report two rare cases of progressive myelopathy caused by intracranial dural
      arteriovenous fistulae with venous drainage into the spinal medullary veins. Both
      patients were referred to us with a history of progressively worsening
      quadriparesis. A posterior fossa dural arteriovenous fistula with spinal venous
      drainage was discovered by angiography in both cases. Treatment consisted of
      direct clipping of the venous drainage in one patient and of transarterial
      embolization and excision of the involved dural sinus in the other patient. Such
      procedures provided a radioanatomical cure and marked neurological recovery in
      both patients. Only 10 cases of progressive myelopathy caused by an intracranial
      dural arteriovenous fistula have been previously reported. Dysfunction of the
      cervical cord by venous engorgement is thought to be the most probable cause of
      the neurological symptoms in such cases.

PMID- 8264895
TI  - Cushing's disease in a child caused by a corticotropin-releasing hormone
      secreting intrasellar gangliocytoma associated with an adrenocorticotropic
      hormone-secreting pituitary adenoma.
AB  - Cushing's disease resulting from intrasellar corticotropin-releasing hormone
      (CRH)-secreting gangliocytomas is very rare, and only two such cases have been
      reported in the literature to date. The authors present a third case in which an
      adrenocorticotropic hormone-secreting pituitary adenoma was found in addition to
      a gangliocytoma in a 10-year-old girl with clinical and endocrinological symptoms
      of Cushing's disease. Computed tomographic and magnetic resonance imaging scans
      showed a suprasellar and parasellar tumor. A green-colored, heterogeneous tumor
      and a small adenoma were removed transsphenoidally. Histological examination
      revealed a large gangliocytoma immunoreactive for CRH and a small, mucoid cell
      pituitary adenoma immunoreactive for ACTH. This is the first case of such a tumor
      causing Cushing's disease in a child. It might exemplify induction of an ACTH
      secreting pituitary adenoma by means of chronic overstimulation of CRH.

PMID- 8264896
TI  - Fusion with occipital bone for atlantoaxial instability: technical note.
AB  - A technique is described of using autologous occipital bone for posterior
      atlantoaxial fusions. The advantages include the ease of harvest, the lack of
      postoperative discomfort, and the suitability of occipital bone for the fusion.

PMID- 8264897
TI  - Selective lumbosacral dorsal rhizotomy immediately caudal to the conus medullaris
      for cerebral palsy spasticity.
AB  - We describe a variation of selective dorsal rhizotomy for spastic cerebral palsy
      that involves sectioning of the dorsal spinal roots immediately caudal to the
      conus medullaris. The operation entails an L1-L2 laminectomy, ultrasonographic
      localization of the conus medullaris, and partial deafferentation of the L1-S2
      roots with electromyographic testing under an operating microscope. In 66
      children with cerebral palsy, the operation reduced spasticity in the lower
      extremity without complications, e.g., motor weakness, neurogenic bladder, and
      sensory loss. It offers several important advantages over alternative techniques.

PMID- 8264898
TI  - Modern bone substitutes with emphasis on calcium phosphate ceramics and
      osteoinductors.

PMID- 8264899
TI  - Modern cranioplasty with hydroxylapatite ceramic granules, buttons, and plates.

PMID- 8264900
TI  - Use of a carbon composite radiolucent anterior cervical retractor system.

PMID- 8264901
TI  - Spinal cord stimulation for chronic, intractable pain: experience over two
      decades.

PMID- 8264902
TI  - Percutaneous trigeminal nerve compression for treatment of trigeminal neuralgia:
      results in 50 patients.

PMID- 8264903
TI  - Segmental neurofibromatosis of the sciatic nerve: case report.

PMID- 8264904
TI  - Syringomyelia in Chiari malformation: relation to extent of cerebellar tissue
      herniation.

PMID- 8264905
TI  - Ceftizoxime versus vancomycin and gentamicin in neurosurgical prophylaxis: a
      randomized, prospective, blinded clinical study.

PMID- 8264906
TI  - 123I-iodobenzamide-SPECT in 83 patients with de novo parkinsonism.
AB  - Single photon emission computed tomography (SPECT) with 123I-iodobenzamide (123I
      IBZM) was used in a prospective study to investigate 83 patients with
      parkinsonism (Hoehn and Yahr stages I to III) who had not been previously treated
      with dopamimetic drugs. All patients had clinical signs that were compatible with
      Parkinson's disease. An additional 13 patients had clinical signs of another
      basal ganglia disorder, such as progressive supranuclear palsy or multisystem
      atrophy. 123I-IBZM-SPECT results were compared with clinical responses to
      subcutaneous injections of the D1/D2-receptor agonist apomorphine (83 patients)
      and to long-term oral dopamimetic therapy (62 patients). Results from 123I-IBZM
      SPECT predicted a positive or negative response to apomorphine in 69 of 76
      patients (apomorphine responses were equivocal in 7 patients) and a response to
      dopamimetic therapy in 54 of 62 patients. All patients with a clinical diagnosis
      of progressive supranuclear palsy or multisystem atrophy had reduced 123I-IBZM
      binding. In six of these patients, the response to apomorphine was negative, and
      none clearly benefited from long-term oral levodopa therapy. Imaging of dopamine
      D2 receptors with 123I-IBZM-SPECT appears to distinguish between patients with de
      novo parkinsonism that is levodopa-responsive (probably Parkinson's disease of
      Lewy body type) and that which does not respond to levodopa therapy.

PMID- 8264907
TI  - Motor response complications and the function of striatal efferent systems.
AB  - Motor response complications eventually appear in most patients with advanced
      Parkinson's disease being treated with levodopa. The interval between onset of
      parkinsonism and emergence of these adverse events appears independent of the
      dose or the duration of therapy. Current evidence suggests that "wearing-off"
      fluctuations largely reflect the loss of normally functioning dopaminergic
      terminals, although postsynaptic alterations contribute somewhat to the
      underlying decline in the duration of levodopa's antiparkinsonian action. "On
      off" fluctuations and peak-dose dyskinesias, on the other hand, appear to arise
      mainly as a consequence of postjunctional alterations that follow exposure to
      nonphysiologic intrasynaptic dopamine fluctuations in patients who have lost the
      buffering afforded by dopaminergic terminals. Studies in rats with 6
      hydroxydopamine lesions indicate that striking functional alterations occur in
      striatal dopaminoceptive systems as a result of dopaminergic denervation and that
      levodopa replacement, particularly when given intermittently, fails to normalize
      these changes. To the extent that similar alterations contribute to the
      appearance of motor complications, the successful symptomatic therapy of
      Parkinson's disease may require continuous dopaminergic stimulation, as well as
      direct pharmacologic targeting of striatal dopaminoceptive systems.

PMID- 8264908
TI  - Clinical and pathophysiologic aspects of late levodopa failure.
AB  - More than 50% of all patients with Parkinson's disease who initially receive
      treatment with conventional levodopa will develop late complications, although
      the underlying mechanisms are not completely understood. Some aspects of levodopa
      peripheral pharmacokinetic handling contribute to response fluctuations, such as
      its short half-life and the variations of gastrointestinal absorption and blood
      brain barrier transport caused by competition with neutral amino acids. In
      themselves, however, these are insufficient to explain the late occurrence of "on
      off" oscillations. Disease-related central changes in presynaptic handling of
      levodopa are likely to play a role, as are postsynaptic pharmacodynamic receptor
      changes, possibly induced by chronic, nonphysiologic, pulsatile stimulation.
      Pharmacodynamic alterations of dopaminergic receptors have also been implicated
      in the pathogenesis of levodopa-induced dyskinesias. Recent experimental findings
      suggest a possible role of downstream functional changes in pallidosubthalamo
      thalamic projections.

PMID- 8264909
TI  - Levodopa therapeutics: new treatment strategies.
AB  - Even though levodopa can provide effective therapy for symptomatic relief of
      parkinsonism, many patients deteriorate over time. This change may be related to
      a loss of storage capability for dopamine in the brain affected by parkinsonian
      changes. Some of the variability in drug action is determined by its peripheral
      pharmacokinetics. Methods that can enhance dose-by-dose effectiveness, including
      controlled-release preparations and enteral infusions, have practical
      applications for managing "wearing-off" or peak-effect problems.

PMID- 8264910
TI  - Psychosocial aspects of Parkinson's disease.
AB  - Although Parkinson's disease has a definite neurologic basis, patients and
      relatives experience a multitude of stresses, only partly related to motor
      symptoms. Subjective and behavioral problems may be regarded as secondary disease
      symptoms. In an integrated approach, patients and relatives receive psychological
      counseling and learn new coping strategies for everyday situations. Results show
      that even elderly patients can make use of structured psychological interventions
      and change dysfunctional behaviors and cognitions. Measures specifically adjusted
      to Parkinson's disease are aimed at helping patients make better use of the
      beneficial effects of medication and counteract the possible negative effects of
      social and emotional stressors. Relatives need information about the disease and
      training to cope adequately with difficult caring situations. Future evaluation
      of medical treatment of Parkinson's disease should consider the interaction of
      psychological factors and symptom intensity. This interaction may result in
      momentary changes in the effects of medication because of psychological
      conditions. In the early stages of the disease, medication has the most positive
      effect, and psychological interventions should also have the most benefit.

PMID- 8264911
TI  - Motor training in the therapy of Parkinson's disease.
AB  - Motor training techniques may be a helpful adjunct to medical treatment in
      improving motor function in patients with Parkinson's disease. Rational physical
      therapy should be based on a detailed understanding of the underlying nature of
      the motor deficit in Parkinson's disease. The design of training techniques
      should take into account the known neurophysiologic aspects of motor impairment
      in Parkinson's disease, such as the inability to initiate movement (akinesia),
      the inability to perform sequential movements, impairments in the pacing of
      rhythmic movements, and impairments in the predictability of movements. Training
      techniques are definitely necessary to prevent the sequelae, especially of the
      later stages of the disease, including contractures and muscle spasm. To increase
      voluntary motor activity, physiotherapeutic approaches must take into account
      specific aspects of the motor control deficit in Parkinson's disease. For
      example, physical therapy should emphasize large-amplitude movements and truncal
      activities and make use of cuing as a major facilitator in achieving rhythmic
      movement patterns. In addition, the psychosocial integration of the patient may
      be improved by physical exercises, particularly if these are provided in group
      therapy sessions.

PMID- 8264912
TI  - Neuropsychological and psychiatric side effects in the treatment of Parkinson's
      disease.
AB  - All medications currently used to treat Parkinson's disease carry some risk of
      causing confusion, hallucinations, or disruption of such higher-order mental
      operations as problem-solving and learning. Although the elderly demented patient
      is at greatest risk, such complications have also been noted during treatment of
      younger patients. Treatment with anticholinergics may lead to a confusional state
      and decreased memory function in some patients, especially the elderly and those
      with preexisting dementia. Monoamine oxidase inhibition is considered quite
      benign when used alone, but may potentiate certain side effects when used in
      combination with other compounds. Ergot alkaloid medication, which is usually
      combined with levodopa, often induces severe psychiatric complications. Typical
      findings with levodopa treatment indicate little or no positive impact on
      cognition, apart from nonspecific arousal and alleviation of concomitant
      depressive affect. Guidelines for the management of neuropsychological and
      psychiatric side effects are suggested.

PMID- 8264913
TI  - PET studies on the early and differential diagnosis of Parkinson's disease.
AB  - A number of neurodegenerative diseases can manifest as parkinsonian disorders.
      Structural imaging, such as CT and MRI, is of limited value for differentiating
      these diseases. PET can demonstrate the selective patterns of disruption of
      regional cerebral metabolism and neurotransmitter systems associated with
      subcortical degenerations, such as Parkinson's disease, striatonigral
      degeneration, progressive supranuclear palsy, and corticobasal degeneration. It
      can also determine, where underlying Parkinson's disease may be suspected,
      whether nigral dysfunction is present in patients with isolated tremor or drug
      associated rigidity. Finally, PET can detect the presence of subclinical
      disruption of the dopaminergic system in at-risk subjects, such as relatives of
      patients with Parkinson's disease, or subjects exposed to nigral toxins, such as
      MPTP. With the advent of putative neuroprotective agents for Parkinson's disease,
      PET can help identify patients with early disease who might benefit from therapy
      with these agents and monitor their disease progression.

PMID- 8264914
TI  - Skin cancer screening in the Army National Guard.

PMID- 8264915
TI  - What is shrapnel?

PMID- 8264916
TI  - Psychiatry and war.

PMID- 8264917
TI  - Health promotion and the flight surgeon.

PMID- 8264918
TI  - Military health care in the 21st century.
AB  - This paper describes the pressures for health care reform which are impinging on
      the United States health care system. These are costs, access, allocation of
      resources, unnecessary care, and administrative costs and confusion. The
      implications of these pressures for military health care are considered to be the
      redefinition of the health benefit, restructuring of the military health care
      system, and questions about the appropriate role for the reserve components. Ten
      persistent issues are identified which will need to be addressed, regardless of
      whatever changes are proposed in the immediate future. These are the quality of
      health care, improved management of the military health care system, costs of
      care including pharmaceuticals, recruitment and retention of health care
      professionals, graduate medical education, renewed emphasis on health promotion
      and disease prevention, discharge planning and patient education, development and
      diffusion of new technologies, information management, and the management of
      environmental waste.

PMID- 8264919
TI  - Testicular carcinoma: a study of knowledge, awareness, and practice of testicular
      self-examination in male soldiers and military physicians.
AB  - Multiple-choice questionnaires devised to evaluate knowledge and awareness of
      testicular carcinoma and the practice of testicular self-examination (TSE) were
      distributed to 717 male soldiers and 200 military physicians in the Israeli army.
      Twenty-one percent of the soldiers had received explanations about the importance
      of TSE; 16% actually received instruction on TSE; yet only 2% practiced TSE
      regularly. Seventy percent of physicians had been taught how to examine
      testicles, but only 10% of physicians examined testicles in their routine
      physical exams. TSE was practiced most frequently among soldiers who had received
      instruction in the technique. Physicians should encourage their young male
      patients to practice TSE.

PMID- 8264920
TI  - Becoming a successful division psychiatrist: guidelines for preparation and
      duties of the assignment.
AB  - Little attention is given in psychiatry residency programs to preparing graduates
      to occupy division psychiatry slots. The first part of this paper discusses
      several guidelines: preparations to make before leaving for a new post; immediate
      steps to take upon arrival; the place of the Division Mental Health Service in a
      division structure; and general observations about how best to obtain credibility
      with line soldiers. The second part focuses on general and specific duties of the
      assignment, and discusses some common clinical problems. The paper is intended to
      help the new division psychiatrists have an effective and productive tour. Many
      sections will be applicable to general medical officers and other health care
      workers leaving for a division assignment.

PMID- 8264921
TI  - Impact of units on rotation at the National Training Center: the Fort Irwin
      MEDDAC experience.
AB  - Soldiers who experience orthopedic injuries during their training cycle at the
      National Training Center have a major impact on the Fort Irwin MEDDAC. The
      majority of hospital referrals from the field medical companies and admissions
      occur during the training days 7 through 20. Vehicular and other training
      accidents result in a mini-MASCAL at least once during the rotation, requiring
      the activation of selected MEDDAC personnel.

PMID- 8264922
TI  - Clinical evaluation of a rapid immunoinhibition assay for creatine kinase-MB in
      suspected myocardial infarction.
AB  - We examined the clinical performance of a new immunoinhibition assay (INH) for
      the measurement of creatine kinase isoenzyme MB (CK-MB). In 196 consecutive
      patients admitted for exclusion of acute myocardial infarction, serial blood
      samples were evaluated by INH, immunoradiometric assay (IRMA), and
      electrophoresis (ELP). Using receiver operating characteristic curve analysis,
      the diagnostic performance of the INH assay was comparable to IRMA and ELP. As
      compared with these alternative methodologies, this newly available INH assay for
      CK-MB provides similar diagnostic accuracy and increased convenience at a greatly
      reduced cost.

PMID- 8264923
TI  - Effects of sedating and nonsedating antihistamines on flying performance.
AB  - The purpose of this double-blind study was to compare the effects on flying
      performance of a nonsedating antihistamine, (terfenadine), two sedating
      antihistamines, (chlorpheniramine and diphenhydramine), and a placebo. Twelve
      USAF pilots were tested at 1-month intervals with the above medications,
      administered during separate testing periods. Medication was given twice daily
      for 3 days. On the third day, each pilot performed three landing approaches in a
      C5-B flight simulator, followed by assessment with psychological and
      neuropsychological tests. Evaluation of the flight data showed no significant
      differences in flight performance among any of the pilots while on four different
      medications. Psychological and neuropsychological testing demonstrated no
      significant differences in performance with the exception of the SCL-90-R, where
      pilots reported psychological and physiological subjective symptoms with
      diphenhydramine and chlorpheniramine, but not with terfenadine. While pilots were
      on each medication, open-ended questionnaires corroborated the results of the SCL
      90-R. Both the flight and neuropsychological testing data suggest that
      terfenadine has no detectable effects on overall flying performance.

PMID- 8264924
TI  - Design, implementation, and preliminary results of an Emergency Medical
      Technician-Intermediate training program on an Air Force installation.
AB  - Design and implementation of an Emergency Medical Technician-Intermediate program
      based on Air Force medical technician training is discussed. Criteria for
      candidate selection is given and course content is outlined. Ambulance use by the
      population as well as response times and success rates for field cardiac arrest
      for a 2-year period are discussed. Recommendations for future development are
      given.

PMID- 8264925
TI  - Combatting traffic accidents in the Israel Defence Forces: the role of the
      Medical Corps.
AB  - A combined plan of action of the Medical Corps in the battle against traffic
      accidents is described. The plan covers sound medical standards for military
      driver licensing, disqualification of drivers with medical problems, reporting of
      problematic drivers (epileptics and others) to the Israeli Ministry of Health,
      evaluating the driving fitness of drivers involved in traffic accidents, and
      finally, an education program for all Israel Defence Forces soldiers to be
      delivered by military physicians. Several medical aspects of traffic safety are
      highlighted. Scientific research and greater involvement of physicians and
      psychologists in this area is required if the trauma occurring daily on highways
      is to be eliminated and acute care hospital costs minimized.

PMID- 8264926
TI  - Mask Performance Rating Table for specific military tasks.
AB  - The Performance Rating Table (PRT) is introduced as a means to separate mask
      wearer performance by causative factors. The PRT shows which mask factors require
      design attention and how the mask affects different users.

PMID- 8264927
TI  - Dental utilization by active duty Army personnel.
AB  - In spring 1989, a random, Army-wide sample of 15,364 enlisted and 4,529 officer
      personnel was surveyed on dental utilization. Results show no difference in
      annual dental utilization between officer and enlisted personnel when age is
      controlled. Because annual dental utilization increases with age and enlisted
      ranks contain a disproportionately large number of younger personnel, a
      difference in annual dental utilization between enlisted and officer personnel
      emerges when age is not controlled. Check-ups are the most common reason for
      dental visits. Nearly all soldiers seek care exclusively in military dental
      clinics. Non-use is highest among 18- to 19-year-olds (12.2%).

PMID- 8264928
TI  - Promotion of a lifestyle conducive to cardiovascular health in the Israel Defence
      Force.
AB  - This article reviews the characteristics and components of intervention programs
      that are conducted by the Israel Defence Forces (IDF) in an attempt to reduce
      future cardiovascular (CV) morbidity and mortality among Israeli military
      personnel. Various populations have been targeted for intervention, ranging from
      selected high-risk individuals to the entire military population. The four basic
      elements of the activity are educational programs, environmental changes,
      legislation, and enforcement of the rules. Important characteristics of the
      program, which probably will contribute to its success, are (1) the establishment
      of a standing joint committee for developing and implementing health promotion
      programs in the IDF; and (2) the adoption and the follow-up of the suggested
      intervention programs by the head of the Manpower Branch, together with
      commanders of the other relevant branches. The effectiveness of the intervention
      programs will be measured in the future mainly by a follow-up on the prevalence
      of CV risk factors among Israeli military personnel.

PMID- 8264929
TI  - Medical devices for military use.
AB  - Medical devices for military use (MDMU) may exist in the following environments:
      fixed health care facilities, long-term emergency storage, and field. This
      article will focus on the unique features and specifications required from MDMU
      in general and in the field in particular. The military clinical engineering
      tasks as they pertain to MDMU with reference to the experience in the Israel
      Defence Forces will be discussed.

PMID- 8264930
TI  - Planning for medical support of disasters.
AB  - Disaster health care plans require that planners consider personnel, equipment,
      supplies (including pharmaceuticals), and logistical support for transportation,
      food, water, and resupply. The authors believe that military Table of
      Organization and Equipment (TOE) hospitals have the potential to be invaluable
      sources of personnel, equipment, and supplies. They recommend that TOE
      organizations plan Military Mobilization Teams (MMTs) that are lightweight,
      rapidly deployable, and easily supported. In addition, MMTs can serve as the
      advance party units around which more complex health care organizations can be
      developed. The same MTTs have potential military uses such as mobilization in
      stages.

PMID- 8264931
TI  - Lyme disease acquired in Europe and presenting in CONUS.
AB  - Lyme disease is recognized in many parts of the world, including large areas of
      North America, Europe, Asia and Australia. Diagnosis and treatment of the disease
      is essential to avoid the debilitating and potentially life-threatening long-term
      effects of the infection; however, many physicians may not be aware of the
      international scope of the disease. This is particularly important for military
      physicians whose patients may visit or live in endemic areas and whose activities
      may bring them in contact with the organism. We report here the case of a soldier
      with near-fatal Lyme carditis acquired in Europe and presenting in Massachusetts.

PMID- 8264932
TI  - Partial subclavian steal.
AB  - The phenomenon of subclavian steal syndrome has recently been found to have a
      subset group that has been described as partial or "pre-steal" in physiology. Our
      case of a Marine Corps pilot with this partial subclavian steal physiology is
      reviewed, in addition to the maneuvers we performed to temporarily convert him to
      complete steal physiology. A discussion of the symptomatology and prognosis of
      this diagnosis is included, with emphasis on military service.

PMID- 8264933
TI  - [The structured abstract].

PMID- 8264934
TI  - [Anesthetic care for fibrobronchoscopy in patients with chronic terminal
      respiratory insufficiency undergoing evaluation for isolated lung
      transplantation].
AB  - During the first 18 month operation of the isolated lung transplantation program
      at or Institution, eight patients with terminal chronic respiratory failure
      underwent fiberoptic bronchoscopy and broncho-alveolar lavage as part of their
      evaluation for isolated lung transplantation. Four patients had severe
      obstructive, three restrictive, and one mixed, obstructive and restrictive,
      disease; all of them were on continuous supplemental oxygen. Procedures were
      performed under topical anaesthesia, with either light sedation or simple
      monitored anaesthesia care. Monitoring included non-invasive blood pressure
      measurement, pulse oximeter and precordial stethoscope. No adverse events were
      recorded, except in one case, when pulse oximeter reading precipitously dropped
      below 80%, to a minimum of 68-69%. The procedures was terminated short of its
      completion, and the patient was briefly assisted with manual bag ventilation on
      oxygen 100%. Pulse oximeter quickly returned to normal levels (above 90%), and
      the patient promptly recovered, without complications. The importance of
      monitored anaesthesia care during fiberoptic bronchoscopy (a usually benign
      procedure) in critically ill patients is greatly emphasized.

PMID- 8264935
TI  - [Anesthesia in the elderly patient. Our experience].
AB  - A study has been carried out in 435 patients over 80 years old underwent elective
      or emergency general surgical operations with general or loco-regional
      anaesthesia in order to evaluate possible risk factors. Preoperative evaluation
      has shown coexisting cardiovascular and respiratory diseases in 68% of patients.
      Treatment of functional decline of organ malnutrition and dehydration and use of
      adequate anaesthesiology management contributed to contain postoperative
      morbidity and mortality compared with other analogue experiences. The authors
      conclude that elderly age, although is a risk factor, cannot be considered an
      absolute contraindication to major surgery. However physiopathological
      modification of the elderly must be evaluate.

PMID- 8264936
TI  - [Pain in pulmonary neoplasms].
AB  - The authors review the cases of 81 patients complaining of pain due to lung
      cancer referred to a Pain Clinic. The cause and characteristics of pain together
      with treatments and results were assessed. The time elapsed from beginning of
      pain complaints to diagnosis, referral to the Pain Clinic and death was
      calculated. The data collected are discussed keeping in mind the aim of providing
      these patients a better quality of life.

PMID- 8264937
TI  - [Effectiveness of low-dose neostigmine in the treatment of sinus tachycardia
      during aortocoronary bypass].
AB  - Thirteen patients, who underwent surgery for myocardial revascularization, were
      given neostigmine, 0.25-1 mg i.v., in order to control intraoperative sinus
      tachycardia. Three minutes after the administration, the drug was effective in
      all patients, by decreasing the heart rate and improving the indices of the risk
      of myocardial ischemia. Seven minutes later the heart rate decreased further. In
      5 patients out of 13, short periods of bradycardia were observed during surgical
      compression or dislocation of the heart. As cardiac rate decreased, P and T waves
      and ST, QT, and QTc intervals lengthened without reaching pathological levels.
      Three minutes after neostigmine, the stroke volume was unchanged in spite of the
      decrease of the heart rate; consequently cardiac index decreased. Seven minutes
      later a slight increase of the stroke volume balanced the further decrease of the
      heart rate; so cardiac index did not change any more. Arterial pressure decreased
      slightly after neostigmine whereas systemic vascular resistance was unaffected.
      Also central venous pressure did not change while pulmonary capillary wedge
      pressure showed a small increase 10 minutes after neostigmine. Finally airway
      resistance did not change significantly.

PMID- 8264938
TI  - [Regional intravenous anesthesia (RIA): a simple method not used frequently].
AB  - We studied 20 outpatients undergoing surgery of the extremities with regional
      intravenous anesthesia (RIA). In our study RIA vas performed with the help of a
      double tourniquet in order to prevent adverse reactions; the drug of choice was
      lidocaine, because we considered it more suitable for this kind of procedure. The
      technique was of simple execution and well tolerated by the patient. This
      technique maker it possible to perform surgery of forearm and foot with a small
      amount of anesthetic even in outpatients.

PMID- 8264939
TI  - [Recovery time after general anesthesia with propofol administered in continuous
      infusion or with isoflurane].
AB  - The recovery time after Propofol-Tiva (P) or Isoflurane-anesthesia (I) for
      elective plastic surgery was studied by the Authors in two series of patients: 60
      in group P, 60 in group I. All patients received a standard premedication and
      induction-anesthesia (premedication: Atropine 0.005 mg/kg i.m.; induction:
      Fentanyl 2.1 micrograms/kg+Propofol 2.5 mg/kg i.m. and Succinylcholine 1 mg/kg
      i.v. for tracheal intubation) and a different maintenance (group P received an
      infusion of 12 mg/kg/h for 10 min, 9 mg/kg/h for the next 10 min and 6 mg/kg/h
      thereafter+Fentanyl 1.4 micrograms/kg/h, group I clinically appropriate inspired
      concentration of Isoflurane and both Fentanyl-bolus at demand). They were
      ventilated mechanically with air and oxygen mixture (FiO2 = 0.3) to maintain
      normal blood-oxygen tension and normocarbia. The results showed that the recovery
      time was significantly shorter in the group P than in the group I and that
      Propofol-Tiva is accompanied by a more rapid recovery than Isoflurane-anesthesia.

PMID- 8264940
TI  - [Idiopathic long QT-syndrome. Changes in the duration of the QTC during
      anesthesia with propofol].
AB  - A prolonged electrocardiographic QTc interval may be unsafe during general
      anesthesia; thus successful anesthetic management in patients affected by
      congenital long QT syndrome include avoidance of any event that increases
      sympathetic activity and drugs that prolong QT interval. Propofol seems to have
      less effect on the QTc interval than tiopentone in normal subjects. This report
      suggest that propofol administration and infusion in clinical doses in a patient
      with Jerwell Lange-Nielsen syndrome may be safe and without increase of duration
      of QTc interval. The most marked changes in HR and QTc followed tracheal
      intubation and awakening suggesting a specific effect of cathecolamines.

PMID- 8264941
TI  - [Urapidil in intraoperative continuous infusion].
AB  - The author reports the results of a clinical experiment with Urapidil
      administered in continue infusion to induce controlled hypotension during
      hemilaminectomies. The reduction of pressure values is obtained after 15-20
      minutes since the beginning of drug infusion (35-40% compared with the starting
      basis values); moreover, because of the double action mechanism of the drug
      (central and peripheral), "reflex tachycardia", a common symptom in hypotensive
      drugs used in the past, disappears. In addition, the author states that the
      absence of potentially toxic degrading metabolites and the lack of "rebound"
      hypertensive phenomena or tachyphylaxia assure very good administration and
      pharmacological security of the drug.

PMID- 8264942
TI  - [General anesthesia without nitrogen monoxide. Its use in abdominal surgery].
AB  - In view of the problems relating to the routine use of nitrogen monoxide in
      general anesthesia, the authors drew up an anesthesiological protocol excluding
      the use of N2O and replacing its analgesic effect with higher doses of fentanyl
      and a higher inspired percentage of isoflurane. Twenty-three patients due to
      undergo abdominal surgery were included in the study. The established anesthetic
      protocol was evaluated by the constant measurement of PAOS/D and heart rate, as
      well as lacrimation and sweating. Satisfactory results were achieved using this
      protocol in almost all patients, although further modifications to the protocol
      are planned to make the technique more stable and manageable.

PMID- 8264943
TI  - [Intensive medicine in metropolitan areas. Update 1992. Multicenter Italian Group
      for the Research in Intensive Care (GIRTI II)].
AB  - This report is an epidemiological study concerning the description of intensive
      care medicine in Italian urban area. 1311 patients were enrolled in 20 ICU during
      a three months period. Mean admission SAPS resulted 13.5 +/- 0.2 point, ICU stay
      7.6 +/- 0.4 days, Hospital stay 21.2 +/- 0.6 days; ICU mortality 24% and hospital
      mortality 31%. With respect to a previous study (1988), the association between
      mortality, severity of disease, admission diagnosis (M, SU, TR, SS) and age
      (particularly with hospital mortality) was confirmed. The study quantify that 18%
      of the mix case had a ICU length of stay less than 24 h. Thirty per cent of these
      patients die. Moreover more than one third of the days of hospital stay occurred
      in ICU with higher figure for COPD, PNM, Mm, CPR, STRK patients. This focuses the
      need for intermediate care units.

PMID- 8264944
TI  - [A case of neonatal extracorporeal membrane oxygenation after heart surgery].
AB  - There is international experience of Extracorporeal Membrane Oxygenation (ECMO)
      in children suffering acute Respiratory failure (eg. meconium aspiration
      syndrome); on the contrary there is a lack of consistent experience in pediatric
      ECMO application in cardiac surgery as bridge to cardiac transplantation and as
      heart mechanical support after postcardiotomy failure. In fact there are good
      standardization criteria for selection, inclusion and exclusion in ECMO
      application for neonatal respiratory failure; differently pediatric ECMO timing
      (that is when to start and to stop this ventricular support) is not clear and
      standardized. We present one case of pediatric ECMO application in a neonate, who
      underwent cardiac operation for pulmonary valve aplasia and who was impossible to
      wean from cardiopulmonary bypass.

PMID- 8264945
TI  - [High risk vascular surgery, anesthesia and tranylcypromine. Description of a
      clinical case].
AB  - The author reports a patient, treated with tranylcipromine as antidepressant (a
      MAO inhibitor), who underwent an operation for abdominal aortic aneurysm. The
      antidepressant was stopped five days only, for neurological problems. The
      anesthesia was a combination among general anesthesia (Diprivan and Tracrium),
      epidural anaesthesia (lidocaine and clonidine) and electro-acupuncture. The
      cardio-circulatory, ventilatory and metabolic parameters were very stable both in
      the perioperative and in the postoperative period.

PMID- 8264946
TI  - Potentiating effects of serotonin and vasoactive intestinal peptide on the action
      of glutamate on suprachiasmatic neurons in brain slices.
AB  - Using extracellular single-unit recording in brain slices, we have tested the
      effects of serotonin and vasoactive intestinal peptide (VIP) on the action of
      glutamate on hypothalamic suprachiasmatic neurons. We hypothesized that serotonin
      and VIP may interact with glutamate so that a modulation of the circadian rhythm
      entrainment to the light-dark may be possible. Given individually, glutamate
      excited 32% and inhibited 1% (n = 65), serotonin excited 8% and inhibited 27% (n
      = 73), and VIP excited 7% and inhibited 7% (n = 41) of suprachiasmatic neurons.
      When administered together, however, serotonin or VIP not only increased the
      percentage of neurons (up to 50%) that responded to glutamate, but also
      potentiated the neuronal responses to glutamate. These findings substantiated our
      hypothesis that both serotonin and VIP may modulate the action of glutamate in
      the suprachiasmatic nucleus.

PMID- 8264947
TI  - Transmitter-like L-3,4-dihydroxyphenylalanine tonically functions to mediate
      vasodepressor control in the caudal ventrolateral medulla of rats.
AB  - By microdialysis in the unilateral caudal ventrolateral medulla (CVLM) of
      anesthetized rats, the spontaneous L-3,4-dihydroxyphenylalanine (L-DOPA) release
      was in part tetrodotoxin-sensitive or Ca(2+)-dependent and was abolished by i.p.
      alpha-methyl-p-tyrosine (alpha-MPT), a tyrosine hydroxylase inhibitor. High K+
      (50 mM) Ca(2+)-dependently evoked L-DOPA. By unilateral microinjections into the
      CVLM, L-DOPA (10-100 ng) produced dose-dependent, marked hypotension and
      bradycardia similarly in rats untreated, treated with i.p. 3
      hydroxybenzylhydrazine, a central DOPA decarboxylase inhibitor, or with i.v.t. 6
      hydroxydopamine. These responses were antagonized by L-DOPA methyl ester, a
      competitive L-DOPA antagonist. A depressor response to dopamine or noradrenaline
      (100 ng) was far smaller and slower in onset than that to L-DOPA (30 ng). D-DOPA
      (100 ng) produced no effect. Furthermore, L-DOPA methyl ester microinjected into
      bilateral CVLM produced some hypertension and tachycardia, which were markedly
      reduced by alpha-MPT. Transmitter-like L-DOPA tonically functions to mediate
      vasodepressor control in CVLM of rats.

PMID- 8264948
TI  - Enteric glial cells are major contributors to formation of cyclic AMP in
      myenteric plexus cultures from adult guinea-pig small intestine.
AB  - Cultures derived from ganglia isolated from the small intestine of adult guinea
      pigs were used to determine relative contribution of neurons and glial cells to
      stimulation of cAMP formation by forskolin in myenteric ganglia. In untreated
      cultures (8-12 days), the ratio of glial cells to neurons was 5-fold higher than
      the ratio in intact myenteric plexus preparations. Treatment with cytosine
      arabinoside virtually eliminated the glia by the 12th day. Microelectrode
      recording of excitatory responses to forskolin in AH/Type 2 neurons confirmed the
      viability of cultured neurons in cytosine arabinoside. Forskolin elevated the
      cAMP content of cultures and cytosine arabinoside reduced this effect by 80-90%.
      This suggests that enteric glial cells are the major contributors to cAMP
      formation in the cultures and that glial cells contribute significantly to
      elevation of cAMP levels seen in intact myenteric ganglia.

PMID- 8264949
TI  - Prion protein is strongly immunolocalized at the postsynaptic domain of human
      normal neuromuscular junctions.
AB  - Using three well-characterized polyclonal and monoclonal antibodies against prion
      protein (PrP), we demonstrated a strong concentration of PrP at human
      neuromuscular junctions (NMJs). Applying double and triple fluorescence-labeling,
      we found that PrP immunoreactivity exactly co-localized with alpha-bungarotoxin
      (alpha-BT) identified acetylcholine receptors, as well as with the high
      junctional concentrations of beta-amyloid precursor protein, beta-amyloid
      protein, desmin, ubiquitin and dystrophin. Therefore, PrP was considered to be
      located on the postsynaptic muscle membrane. At all NMJs identified by bound
      alpha-BT, strong PrP immunoreactivity was obtained with all PrP antibodies. This
      appears to be the first demonstration of PrP concentrated at human NMJs.

PMID- 8264950
TI  - Self-generated rapid taps directed to the opposite forearm in man: anticipatory
      reduction in the muscle activity of the target arm.
AB  - A brief hammer tap applied passively (by the experimenter) to the forearm elicits
      a short-latency reflex response in the forearm flexors and extensors. When the
      same tap is performed actively (by the subject) using the opposite forearm, the
      reflex response is preceded by a short-lasting anticipatory reduction in the
      muscle activity appearing around the impact. This anticipatory reduction is
      interpreted as an alternative mode of feedforward motor control associated with
      damping of kinetic impulses generated within the bimanual system.

PMID- 8264951
TI  - Dexamethasone abolishes the activation by nerve growth factor of protein kinase
      N: effects of nerve growth factor and dexamethasone on protein kinase N.
AB  - Protein kinase N (PKN) is a basic 45-47 kDa serine/threonine protein kinase
      activated by NGF and several other factors in PC12 cells and other cell types. It
      is inhibited in vitro by purine analogs. In this work, we further characterize
      the modulation of PKN activity following exposure of PC12 cells to dexamethasone
      or NGF, which respectively direct these cells towards the chromaffin- or neuron
      like phenotype. We show here that the two factors elicit opposite effects on the
      activation of the kinase: dexamethasone inhibits while NGF stimulates the basal
      level of PKN activity. Simultaneous addition to the cells of the factors causes
      no variation from basal kinase activity. Addition of dexamethasone not to the
      cells, but to partially purified PKN during the kinase assay, causes no
      modulation of the enzyme.

PMID- 8264952
TI  - Adenosine antagonists prevent hypoxia-induced depression of excitatory but not
      inhibitory synaptic currents.
AB  - Hypoxia induces depression of excitatory postsynaptic currents (EPSCs) and
      inhibitory postsynaptic currents (IPSCs) in CA1 neurons of the hippocampus. The
      effect of antagonists that act at the A1 adenosine receptor on hypoxia-induced
      depression of EPSCs and IPSCs were examined in hippocampal slices with the patch
      clamp technique (whole-cell configuration). The A1 receptor antagonists 8
      cyclopentyl-1,3-dipropylxanthine (DPCPX) (200 nM) and 8-phenyltheophilline (8-PT)
      (10 microM) significantly prevented depression of EPSCs by hypoxia but failed to
      protect IPSCs. This result suggests that the hypoxia-induced depression of the
      EPSC involves the activation of adenosine receptors (possibly of the A1 subtype),
      whereas depression of the IPSC results from a different mechanism.

PMID- 8264953
TI  - The interaction between locomotion, striatal dopamine and paramedian reticular
      nucleus in rats.
AB  - Either intact rats, sham-operated rats, or rats with lesions of the paramedian
      reticular nucleus (PRN) were exposed to cold (2 degrees C) or heat (36 degrees C)
      stress and their locomotor activity responses and striatal dopamine (DA) release
      were compared. At room temperature (22 degrees C), results analyzed revealed
      significant effects in the PRN-lesioned rats: increases in locomotion (including
      both horizontal and vertical motion), direction of turnings (including both
      clockwise and anticlockwise) or striatal DA release. In both the intact rats and
      the sham-operated rats, either cold or heat stress increased the locomotion, the
      direction of turnings and the striatal DA release. The increases in both vertical
      motion and striatal DA release following cold or heat stress were attenuated by
      PRN lesions. The data suggest that a PRN-striatal DA link existing in rat's brain
      which affects both the spontaneous and the thermal stress induced locomotor
      activities.

PMID- 8264954
TI  - Neurohormone D increases the intracellular Ca2+ level in cockroach neurones
      through a Cd(2+)-sensitive Ca2+ influx.
AB  - The modulating effect of the octapeptide neurohormone D (NHD) on the
      intracellular calcium level [Ca2+]i of neurones from the dorsal midline of the
      cockroach terminal ganglion was investigated with fluorescence measurements.
      [Ca2+]i of cells loaded with Fura 2 was determined by photon counting and imaging
      at wavelengths of 340 and 380 nm. After application of NHD, [Ca2+]i increased
      within 3 min from a value of 93 +/- 36 nM to 153 +/- 51 nM, corresponding to an
      enhancement to 164 +/- 35%. In Ca(2+)-free solution, [Ca2+]i was lowered (52 +/-
      6 nM) and NHD no longer affected the intracellular calcium level. The presence of
      0.1 mM Cd2+, in normal saline, prevented the NHD-induced increase of [Ca2+]i. The
      results were explained by postulating a Ca2+ resting current in these cells which
      is augmented by NHD.

PMID- 8264955
TI  - Ammonia-induced alterations in the activities of synaptosomal cholinesterases of
      rat brain under in vitro and in vivo conditions.
AB  - Effects of in vivo and in vitro pathophysiological concentrations of ammonium
      acetate were studied on the activities of acetyl and pseudocholinesterases in the
      synaptosomes isolated from cerebral cortex, cerebellum and brain stem of rat
      brain. Administration of subacute and acute doses of ammonium acetate elevated
      the activities of both the cholinesterases in synaptosomes of all the above three
      regions. A linear relationship (r = 0.98) was observed between brain-ammonia
      levels and magnitude of elevation in the activities of cerebral cholinesterases.
      Kinetic analysis revealed that this elevation was due to a change in the Vm but
      not in the Km of the enzymes. Incubation of synaptosomes isolated from normal
      animals with 1, 5 and 10 mM ammonium acetate marginally elevated the activities
      of these enzymes and had no effects on purified enzyme. It is suggested that the
      changes in the activities might be due to altered architecture of the membranes
      which exposes more number of catalytic sites.

PMID- 8264956
TI  - ATP-sensitive K+ channel activators suppress the GABAergic inhibitory
      transmission by acting on both presynaptic and postsynaptic sites in rat cultured
      hippocampal neurons.
AB  - Effects of ATP-sensitive K+ (KATP) channel activators on the inhibitory
      transmission were explored by applying the patch-clamp technique to both
      presynaptic and postsynaptic hippocampal neurons prepared from neonatal rats.
      Diazoxide (0.5 mM) and cromakalim (0.5 mM) reduced GABAergic synaptic currents to
      57 and 81% of control, respectively, and reduced the currents induced by
      exogenously applied GABA (10 microM) to 74 and 95% of control, respectively.
      These results suggest that KATP channel activators suppress the GABAergic
      transmission partly by reducing the GABA release and partly by affecting the
      postsynaptic GABA response.

PMID- 8264957
TI  - Effects of ageing on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      neurotoxic effects on striatum and brainstem in the rat.
AB  - In 3- and 18-month-old male Wistar rats, levels of dopamine (DA),
      dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid
      (DHAA), noradrenaline (NA), uric acid, glutathione (GSH) and 1-methyl-4
      phenylpyridinium ion (MPP+) were determined by HPLC in the striatum and/or in the
      brainstem 24 h after single injections of MPTP (12-35 mg/kg i.p.). Aged rats had
      lower baseline levels of AA and GSH, compared to young rats. In aged rats, MPTP
      35 mg/kg induced a 70% death rate and a decrease in striatal DOPAC/DA ratio which
      was significantly correlated to MPP+ concentrations (r = -0.840, P < 0.005); in
      addition, MPTP did not increase AA oxidation. In the brainstem, the MPTP-induced
      decrease in NA levels and increase in uric acid levels were significantly
      correlated to the MPP+ concentrations (r = -0.709, P < 0.05, and r = +0.888, P <
      0.001, respectively). In conclusion, evidence is given of a mechanism of toxicity
      of MPTP involving oxidative stress produced by xanthine oxidase; in addition, in
      aged rats the neuronal antioxidant system (levels of AA and GSH) is considerably
      lower than in young rats and may play an enabling role in the MPTP age-related
      neurotoxic effects on striatum and brainstem.

PMID- 8264958
TI  - Ganglioside GM1 cooperates with brain-derived neurotrophic factor to protect
      dopaminergic neurons from 6-hydroxydopamine-induced degeneration.
AB  - Brain-derived neurotrophic factor (BDNF) has recently been shown to enhance the
      survival of dopaminergic neurons in cultures derived from the embryonic rat
      mesencephalon. In the present study BDNF was found to protect cultured
      dopaminergic neurons from injury induced by acute exposure to the dopaminergic
      selective neurotoxin 6-hydroxydopamine. The BDNF effect was concentration (ED50
      approximately 10 ng/ml) and time-dependent, as determined by tyrosine hydroxylase
      immunocytochemistry. More importantly, subthreshold amounts of BDNF were rendered
      efficacious in the presence of ganglioside GM1: loss of tyrosine hydroxylase
      positive cells was reduced from 80% to only 20%. Thus GM1 may provide a fruitful
      treatment strategy for disorders of dopamine function such as Parkinson's
      disease.

PMID- 8264959
TI  - Haemorrhage-induced production of Fos in neurons of the lamina terminalis: role
      of endogenous angiotensin II.
AB  - Hypotensive haemorrhage increased the production of Fos, a marker of cell
      activation, in cells of the subfornical organ (SFO) and the organum vasculosum of
      the lamina terminalis (OVLT) as well as in the supraoptic (SON) and
      paraventricular (PVN) nuclei in conscious rats. Pretreatment with captopril (100
      mg/kg i.p.) inhibited the production of Fos in cells of the SFO and OVLT but did
      not reduce the concentration of Fos-positive cell nuclei in the PVN and SON. The
      results suggest that the production of Fos in the SFO and OVLT induced by the
      haemorrhage is probably due to elevated levels of circulating angiotensin II.

PMID- 8264960
TI  - Immortalization of a cell line showing some characteristics of the
      oligodendrocyte phenotype.
AB  - We have used the polyoma middle T oncogene to immortalize cells from rat embryo
      encephalon. Immunostaining experiments with monoclonal antibodies demonstrated
      that the cells of one of the obtained lines, named CEINGE CL3, are stained by
      anti-vimentin and anti-S100 antibodies, are not stained by anti-neurofilaments
      (NF) or anti-glial fibrillary acidic-protein (GFAP) antibodies. Only a subset of
      the CEINGE CL3 cells (20-30%) is stained by an anti-galactocerebroside antibody.
      Northern blot analysis demonstrated that these cells express low levels of
      proteolipid protein mRNA, whereas polymerase chain reaction (PCR) amplification
      failed to evidentiate the presence of both NF and GFAP mRNAs. Either retinoic
      acid or forskolin treatments or a combination of them are able to induce
      morphological changes that are accompanied by a complete growth arrest.

PMID- 8264961
TI  - The plant lectin Bandeiraea simplicifolia I-B4 identifies a subpopulation of
      small diameter primary sensory neurones which innervate the skin in the rat.
AB  - In recent years a variety of glycoconjugates have been found associated with the
      plasma membrane of mammalian primary sensory neurones. The functional
      significance of these glycoconjugates remains obscure but their carbohydrate
      chains have been widely implicated in cell-cell recognition (or adhesion) during
      development. The plant lectin Bandeiraea simplicifolia I-B4 identifies a
      characteristic galactose-containing glycoconjugate associated with small diameter
      primary sensory neurones. In this study we have used a combination of lectin
      binding and retrograde tracing to examine the distribution of this glycoconjugate
      on sensory neurones which innervate different target tissues in the rat. The
      fluorescent tracer diamidino yellow was applied the cut end of peripheral nerves
      which selectively innervate either the skin, muscle or viscera. Retrogradely
      labelled neurones were then screened for lectin binding using a lectin
      horseradish peroxidase conjugate. The results revealed that Bandeiraea
      simplicifolia I-B4 binding is associated with over one-third of neurones which
      innervate the skin, but only a small proportion of neurones innervating muscle or
      viscera.

PMID- 8264962
TI  - Vasopressin mRNA in the cerebellum and circumventricular organs: a quantitative
      in situ hybridization study.
AB  - To answer the question as to whether vasopressin is synthesized in brain
      structures other than the supraoptic and paraventricular nuclei of the
      hypothalamus, vasopressin mRNA was detected by in situ hybridization in the
      pituitary, cerebellum, dentate gyrus, habenula and circumventricular organs. The
      highest levels (0.3-0.2 pmol/g), measured by quantitative autoradiography, were
      observed in the pituitary intermediate lobe and the granular layers of the
      cerebellum and dentate gyrus. Lower levels (0.15-0.08 pmol/g) were found in the
      medial habenula, adenohypophysis, area postrema, pineal, subfornical and
      subcommissural organs.

PMID- 8264963
TI  - Evidence for a new, high-molecular weight isoform of protein kinase C in rat
      hippocampus.
AB  - We describe a new form of protein kinase C (PKC) with a molecular weight of 97
      kDa, higher than the known forms of vertebrate PKC. This putative new high
      molecular weight isoform, which we are calling PKC (HMW), is increased in the
      membrane fraction either upon application of phorbol esters or with afferent
      synaptic stimulation of Schaffer collaterals in hippocampal slices. The protein
      cross-reacts on immunoblot with affinity-purified polyclonal antiserum raised
      against a peptide derived from the carboxy-terminus of PKC eta; it does not cross
      react, however, with antiserum against the amino-terminal region of PKC eta. In
      the tissues examined, PKC(HMW) is localized primarily in brain, in contrast to
      PKC eta, which is found predominantly in lung and skin.

PMID- 8264964
TI  - Intra-hippocampal injection of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)
      inhibits partial and generalized seizures induced by kindling stimulation in
      cats.
AB  - This study assessed the effects of microinjections of a serotonin (5-HT) 1A
      agonist, 8-OH-DPAT, into the feline hippocampus (HIP) on seizure response induced
      by electrical stimulation of this region. Intra-HIP injection of 8-OH-DPAT (10
      nmol) produced a significant elevation in the afterdischarge threshold of partial
      HIP seizures, with a significant reduction in the duration of focal
      afterdischarge. Similarly, microinjection of 8-OH-DPAT at the same dose
      significantly raised the seizure threshold for eliciting generalized seizures in
      HIP-kindled cats. The present results demonstrate that focally applied 8-OH-DPAT
      possesses a potent anticonvulsant action, and provide further evidence for the
      inhibitory role of 5-HT1A receptors in the generation of HIP seizures.

PMID- 8264965
TI  - Amyotrophic lateral sclerosis: quantitative autoradiography of [3H]MK-801/NMDA
      binding sites in spinal cord.
AB  - We have characterized a high-affinity binding site for [3H]MK-801, an NMDA
      receptor ion channel antagonist, in cervical spinal cords from patients who have
      died with amyotrophic lateral sclerosis (ALS) and from control subjects. In
      cervical spinal cord [3H]MK-801 labelled at least two binding sites, the highest
      affinity site having a Kd of between 9-16 nM. No significant differences in
      affinity were observed between spinal cords from ALS patients or controls. In
      spinal cords from ALS patients, large reductions in [3H]MK-801 receptor binding
      (between 30-40% reductions) were detected in both the dorsal and ventral horns.
      These data may reflect the death of receptor-bearing cells, or a form of receptor
      regulation.

PMID- 8264966
TI  - Different degrees of processing of secretogranin II in large dense core vesicles
      of bovine adrenal medulla and sympathetic axons correlate with their content of
      soluble PC1 and PC2.
AB  - We investigated the processing of secretogranin II in large dense core vesicles
      of adrenal medulla and sympathetic nerve. Despite the fact that both types of
      vesicles have a very similar biochemical composition, the degree of processing of
      secretogranin II in vesicles from splenic nerve was significantly higher. The
      endoproteases PC1 and PC2, two likely candidates for secretogranin II cleavage,
      are found in both types of vesicles, however, relative to secretogranin II the
      nerve vesicles have a much higher content of these enzymes. This probably
      explains the fast and more extensive processing of secretogranin II in these
      vesicles.

PMID- 8264967
TI  - Neurite outgrowth of spinal neurons on tissue sections of embryonic muscle is
      largely integrin dependent.
AB  - Embryonic chick spinal neurons have been cultured over sections of human foetal
      muscle to determine which cell adhesion molecules present in embryonic muscle are
      important in promoting neurite outgrowth. Using blocking antibodies against the
      major cell adhesion molecules, neural cell adhesion molecule (NCAM), N-cadherin
      and the beta 1 subunit of the integrins, neurite outgrowth was significantly
      blocked only by anti-integrin antibodies. In addition other agents that block
      neurite outgrowth stimulated by NCAM, N-cadherin and L1, such as the calcium
      channel antagonists verapamil and omega-conotoxin and pertussis toxin which
      inactivates G-proteins also had no effect. This suggests that in this culture
      system integrins are able to promote neurite outgrowth whereas NCAM and N
      cadherin are not.

PMID- 8264968
TI  - No age-related changes in human benzodiazepine receptor binding measured by PET
      with [11C]Ro 15-4513.
AB  - The effects of age on the binding of [11C]Ro 15-4513, a partial inverse agonist
      of the central benzodiazepine receptor, were studied. Sixteen healthy male
      volunteers (21-78 years old) participated. Regional radioactivity in the brain
      was followed for 45 min by positron emission tomography after a bolus injection
      of [11C]Ro 15-4513. Similar tracer kinetics were observed in both young and old
      subjects. For the quantification of receptor binding in vivo, a compartment
      model, in which radioactivity in the pons was used as an input function, was
      applied. There were no significant changes in the binding potentials with age (P
      > 0.1) in ten brain regions. These observations delineate an interesting
      difference between central benzodiazepine (BZ) receptors and other
      neurotransmitter receptors in the human brain measured by PET that have been
      shown to have a reduction with age.

PMID- 8264969
TI  - Changes in cortical field potentials during learning processes of go/no-go
      reaction time hand movement with tone discrimination in the monkey.
AB  - Field potentials were recorded with electrodes implanted in various cortical
      areas while a monkey acquired a task of go/no-go reaction time hand movement with
      discrimination between tone stimuli of different frequencies. After a few weeks
      of training, a surface-negative, depth-positive (s-N, d-P) potential (no-go
      potential) emerged in the dorsal bank of the principal sulcus. As the potential
      increased in size in 1-3 months, the monkey gradually discriminated between go
      and no-go stimuli. The no-go potential is considered to be related to judgement
      not to move and suppression of motor execution. In the superior temporal gyrus, a
      s-N, d-P potential at a shorter latency than the no-go potential augmented in
      size on both go and no-go trials, as the monkey learned the discrimination task.
      The s-N, d-P potential in this gyrus may reflect an information processing prior
      to the discrimination in the prefrontal cortex.

PMID- 8264970
TI  - Effect of iron and estrogen on melatonin secretion by the chicken pineal gland.
AB  - Estrogen effects on pineal secretion of melatonin are controversial. Some feel
      that estrogen inhibits melatonin output in vitro but not in vivo. Melatonin
      levels vary with the age in chickens where circulating estrogen levels also vary.
      Laying hens have minimal melatonin levels and maximal serum iron concentrations.
      Thus, we reasoned that iron released by estrogen may inhibit melatonin secretion
      from the chick pineal gland. The present study shows that perifusion of estrogen
      treated chick pineal glands with several concentrations of iron greatly inhibited
      melatonin secretion.

PMID- 8264971
TI  - Capsaicin-induced central facilitation of a nociceptive flexion reflex in humans.
AB  - The effect of selective activation of nociceptive primary afferent fibers by
      capsaicin on a nociceptive lower limb flexion reflex was studied in healthy human
      subjects. Capsaicin (1%) applied topically to the skin produced a burning
      spontaneous pain sensation and allodynia in the treated region and in its
      immediate vicinity. Capsaicin applied to the distal innervation area of the sural
      or saphenous nerve produced a significant decrease of the threshold for the
      nociceptive limb flexion reflex induced by electric stimulation of the proximal
      sural nerve trunk, and this threshold decrease was rapidly attenuated by a cool
      compress concomitantly with the attenuation of the capsaicin-induced spontaneous
      pain. The latency of the flexion reflex response was not changed by capsaicin.
      The non-nociceptive H-reflex was not modified by capsaicin. It is concluded that
      a selective activation of nociceptive primary afferent fibers of the skin by
      capsaicin produces a central facilitation of a nociceptive flexion reflex in
      humans. This facilitation is selective on the nociceptive reflex and depends, at
      least partly, on the on-going afferent barrage in C-fibers.

PMID- 8264972
TI  - Central action of C-type natriuretic peptide on vasopressin secretion in
      conscious rats.
AB  - The effect of intracerebroventricular injection of C-type natriuretic peptide
      (CNP) on arginine vasopressin (AVP) secretion was studied in conscious rats, and
      was compared to that of atrial natriuretic peptide (ANP). The AVP secretion
      induced by central injection of 0.1 nmol angiotensin II was significantly
      suppressed by the pretreatment with 1 nmol CNP. ANP at a dose of 0.1 nmol
      elicited almost equivalent suppressive action to 1 nmol CNP. Considering that CNP
      is a specific ligand for ANP-B receptor, while ANP is that for ANP-A receptor,
      the result demonstrates that CNP possesses the similar central action to ANP, and
      suggests that the distribution of ANP-A and ANP-B receptors and/or their affinity
      towards each natriuretic peptide are different in the central nervous system.

PMID- 8264973
TI  - Immunoreactive corticotropin-releasing hormone levels in discrete hypothalamic
      nuclei of genetically obese Zucker rats.
AB  - The levels of immunoreactive corticotropin-releasing hormone (ir-CRH) were
      measured in discrete hypothalamic nuclei and the median eminence of obese Zucker
      rats and their lean littermates. More than 90% of total hypothalamic ir-CRH was
      detected in the median eminence in both obese and lean rats. Though ir-CRH levels
      in the paraventricular nucleus of obese rats tended to be lower than those of
      their lean littermates, no significant difference of ir-CRH levels was observed
      in any hypothalamic nuclei studied between obese and lean rats. However, ir-CRH
      levels in the median eminence of obese rats were significantly lower than those
      of their lean littermates (5263 +/- 438 pg/tissue vs. 7050 +/- 473 pg/tissue, P <
      0.05). These results suggest that the hypoactive hypothalamic CRH tonus would
      play some role in the phenotypic expression of obesity in the genetically obese
      Zucker rats.

PMID- 8264974
TI  - Ultrastructural demonstration of exocytosis of neurosecretory granules in the
      neurohypophysis of the frog Rana temporalia.
AB  - The release of neurosecretory granules by exocytosis was ultrastructurally
      observed in the neurohypophysis pars nervosa (posterior lobe) of the frog Rana
      temporalia with the tannic acid-Ringer fixation method. Electron microscopic
      analysis with the immunogold method revealed that many of putative neurosecretory
      granules displayed oxytocin-like immunoreactivity.

PMID- 8264975
TI  - Human auditory cortex responses to rising versus falling glides.
AB  - A 24-channel SQUID magnetometer was used to record signals from the right
      auditory cortex to tone glides with 16 different centre frequencies (ranging from
      0.5 to 2 kHz), sweeping over one octave. The stimulus sequence, presented with an
      interstimulus onset interval of 0.6 s, consisted of infrequent 'deviant' rising
      (falling) glides and frequent 'standard' falling (rising) glides; the rising
      glides were identical to the falling glides but presented in the reverse
      direction. Deviant glides elicited significantly larger responses than standards
      at a latency of about 100 ms. This amplitude difference presumably arises from a
      mismatch response to the deviants. These results suggest that the auditory cortex
      extracts the direction of frequency transition even when the stimuli do not
      contain same frequencies.

PMID- 8264976
TI  - Interaction of zinc with ionotropic and metabotropic glutamate receptors in rat
      hippocampal slices.
AB  - The actions of zinc on ionotropic and metabotropic glutamate receptors were
      studied using intracellular recording in acutely prepared adult rat hippocampal
      slices and in organotypic hippocampal slice cultures. In control Krebs, glutamate
      and non-N-methyl-D-aspartate (NMDA) agonist-induced responses were enhanced by
      zinc (25-300 microM). However, under conditions favouring NMDA receptor
      activation, zinc inhibited glutamate- and NMDA-induced responses. Metabotropic
      glutamate receptor-mediated responses activated in cultured slices by 1-amino
      cyclopentane-1,3-dicarboxylate (1S,3R-ACPD) or by quisqualate, were reversibly
      inhibited by zinc (200 microM). These results indicate that zinc can inhibit
      responses induced by activation of metabotropic glutamate receptors and reaffirm
      that zinc has a differential effect on NMDA and non-NMDA receptors.

PMID- 8264977
TI  - Passive biophysical membrane properties of nucleus reticularis gigantocellularis
      neurons in brain slices from the rat.
AB  - This study employed intracellular recording coupled with the current clamp
      technique to characterize the passive biophysical membrane properties of neurons
      in the nucleus reticularis gigantocellularis (NRGC) of brain slices from adult,
      male Sprague-Dawley rats. We found that NRGC neurons possessed highly depolarized
      transmembrane potentials (-22.9 +/- 0.6 mV, n = 189). The 29 NRGC neurons that
      received further evaluation showed that they could be separated into two
      clusters, with significantly different membrane input resistances (3.51 +/- 0.89
      vs 77.50 +/- 8.82 M omega) and membrane time constants (0.56 +/- 0.05 vs 1.27 +/-
      0.12 ms). These membrane properties, which resembled qualitatively those we
      observed previously in cats in vivo, will form the basis for further evaluation
      of the ionic mechanisms that may underlie the actions of pharmacologic agents on
      the NRGC neurons.

PMID- 8264978
TI  - MK-801, an N-methyl-D-aspartate receptor antagonist, blocks quinolinic acid
      induced lipid peroxidation in rat corpus striatum.
AB  - In this study, we evaluate the possible participation of lipid peroxidation (LP)
      in the neurotoxic events that follow after quinolinic acid (QUIN) microinjection
      into the rat corpus striatum. Two hours after QUIN (240 nmol/microliters)
      intrastriatal administration, lipid peroxidation was found increased by 32% vs.
      control as measured by thiobarbituric acid-reactive substances (TBARS). At the
      same time tested, the enhancement in LP was of 55% vs. control as measured by
      lipid fluorescent products (LFP) formation (a second index of lipid peroxidation
      employed). The increase of QUIN-induced lipid peroxidation was completely
      abolished by pretreatment of rats with an N-methyl-D-aspartate (NMDA) receptor
      antagonist, MK-801 (10 mg/kg, i.p.), 60 min before QUIN microinjection. Results
      suggest an NMDA receptor involvement in the QUIN-induced oxidative processes.

PMID- 8264979
TI  - Molecular properties of the glutamate receptor mediating synaptic excitation in
      rat hypothalamic neurons.
AB  - AMPA-type glutamate receptors (GluRs) mediate synaptic excitation in networks of
      cultured rat hypothalamic neurons [18, 25]. Under voltage clamp the agonists
      quisqualate and AMPA induce current responses which consist of a maintained
      and/or transient component depending on the concentrations applied. The current
      voltage relationship for both components is linear. The biphasic response
      patterns are due to receptor desensitization which is fast and does not require
      intracellular second messengers for its activation. Several GluR-subtype-encoding
      transcripts were found in these neurons using polymerase chain reaction (PCR)
      methods. While mRNAs encoding the GluR2 and 3 flip forms are expressed early,
      mRNAs encoding the GluR1, 2 and 3 flop forms and the GluR4 flip form appear only
      in cultures older than 3 weeks. By comparison to recombinant receptors, the
      properties of the native receptor can be accommodated by a heteromeric receptor
      containing GluR2 as one of the subunits.

PMID- 8264980
TI  - Thienyl-GABA derivatives as specific baclofen agonists in the rat and cat spinal
      cord in vivo.
AB  - The depression of the amplitude of extracellularly recorded monosynaptic
      excitatory field potentials in the lumbar spinal cord of pentobarbitone
      anaesthetised rats and cats by three thienyl derivatives of GABA: 4-amino-3-(2
      thienyl)-butanoic acid; 4-amino-3-(2-thienyl-5-methyl)-butanoic acid and 4-amino
      3-(2-thienyl-5-chloro)-butanoic acid was reversibly blocked by the (-)-baclofen
      antagonist 3-aminopropyl-diethoxymethyl-phosphinic acid (CGP 35348). These
      compounds, of which the most potent, the 5-chloro derivative, was weaker than (-)
      baclofen, thus activate baclofen receptors in the cat and rat spinal cord.

PMID- 8264981
TI  - Involvement of NPY-immunoreactive neurons in the cerebral cortex of amyotrophic
      lateral sclerosis patients.
AB  - We performed a quantitative histochemical study of neuropeptide Y (NPY)
      immunoreactivity in postmortem human brain to further define patterns of neuronal
      degeneration in amyotrophic lateral sclerosis (ALS). The density of NPY fibers
      was decreased in ALS motor cortex but not in other cortical regions or striatum.
      Although, the density of cortical NPY neurons was unchanged in high grade cases,
      neurons were shrunken and atrophic with pruned dendrites. NPY neurons are less
      severely affected than parvalbumin neurons which are severely depleted in ALS
      cortex. This differential involvement of local circuit neurons suggests that a
      simple excitotoxic model may not adequately explain patterns of neuronal loss in
      ALS.

PMID- 8264982
TI  - Distribution of NADPH-diaphorase positive nerve fibers in the rat nasal mucosa.
AB  - Nasal mucosa was investigated by NADPH-diaphorase histochemistry. Positive fibers
      were distributed around blood vessels, seromucous glands and in the subepithelial
      layer. The pterygopalatine, trigeminal and superior cervical ganglia were also
      studied to examine the origin of these fibers. Many neurons in the
      pterygopalatine ganglion were labeled, and a few neurons were stained in the
      trigeminal ganglion. No perikarya were labeled in the superior cervical ganglion.
      Therefore, most of the labeled fibers must be originating from the
      pterygopalatine ganglion, and the rest of them may originate from the trigeminal
      ganglion. These results suggest that nitric oxide may have some role in the
      nervous control of the nasal mucosa.

PMID- 8264983
TI  - Monkey hippocampal neuron responses related to spatial and non-spatial influence.
AB  - Activity in the monkey hippocampal formation (HF) was analyzed during movement
      guided by auditory and visual cues. The monkey could control a motorized cab by
      pressing the proper 1 of 4 available levers within a 2.5 x 2.5 m field. Of 238 HF
      neurons analyzed, responses of 79 were place related and responses of 110 were
      task related. Of the task-related neurons, 33 were also place related, and
      responded to task cues only where place-related responses occurred. The results
      suggest HF gating of incoming non-spatial information, depending on information
      about location.

PMID- 8264984
TI  - Abdominal surgery induces c-fos expression in the nucleus of the solitary tract
      in the rat.
AB  - In a model of abdominal surgery, which consisted of cecal manipulation and
      induces postoperative ileus in rats, we studied c-fos protein expression in the
      nucleus of the solitary tract (NTS), the spinal cord and dorsal root ganglia.
      Abdominal surgery resulted in a significantly higher number of c-fos protein
      immunoreactive cells in the NTS compared with controls but not in dorsal root
      ganglia and resulted in only a few scattered cells in the spinal cord. Neurons
      expressing c-fos protein were concentrated in NTS regions where cecal afferents
      terminate. These findings support the hypothesis that sensory vagal pathways
      partly mediate abdominal surgery-induced postoperative ileus.

PMID- 8264985
TI  - Ceruloplasmin levels in the human superior temporal gyrus in aging and
      Alzheimer's disease.
AB  - In the present study we observed a loss in excess of 1/3 of the copper transport
      and anti-oxidant protein ceruloplasmin in both the gray and white matter from
      superior temporal gyrus in Alzheimer's diseased brains compared to age-matched
      controls. A decrease in ceruloplasmin could be reflected in decreased cellular
      metabolic processes such as the electron transport system and a decrease in the
      ability of the brain to protect itself from oxidative damage. Both decreased
      metabolic activity and an increase in oxidative insults are known to be
      associated with the neurological events in Alzheimer's disease, but the mechanism
      by which these phenomena occur are unknown. These results coupled with previous
      reports from this laboratory on iron regulatory proteins in the brain suggests
      one way in which cellular dysfunction and oxidative stress occurs in AD may be
      through a loss of ability to maintain a balance of essential metals.

PMID- 8264986
TI  - Participation of nucleus reticularis gigantocellularis in the antinociceptive
      effect of angiotensin III in the rat.
AB  - We evaluated the participation of nucleus reticularis gigantocellularis (NRGC), a
      medullary nucleus that plays an important role in the regulation of nociceptive
      processes, in the antinociceptive effect of angiotensin III (AIII), a
      biologically active peptide of the renin-angiotensin system. Adult, male Sprague
      Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10
      mg/kg/h i.v. infusion supplement) were used. Bilateral, site-specific
      microinjection of AIII (80 or 160 pmol) into the NRGC produced a dose-related
      increase in the latency of tail-flick response to noxious thermal stimuli (50
      degrees C hot water). Such an antinociceptive action of AIII was blocked by
      concomitant administration of the AIII receptor antagonist, Ile7-angiotensin III
      (Ile7-AIII, 10 nmol). At the neuronal level, microiontophoretic application of
      AIII suppressed, Ile7-AIII reversibly, the responsiveness of nociception-related
      neurons in the NRGC to tail-clamping. These results demonstrated that central
      AIII may elicit antinociception via a process that may at least take place at the
      NRGC.

PMID- 8264987
TI  - Isoflurane prevents transitions to tonic and burst firing modes in thalamic
      neurons.
AB  - We used patch-clamp whole-cell techniques to assess the effects of a volatile
      anaesthetic on thalamic firing modes in rat brain slices. Isoflurane application
      in clinical concentrations (0.5-2%) reversibly prevented voltage-dependent
      transitions to repetitive spike and burst firing modes in ventrobasal neurons. In
      voltage-clamp studies, isoflurane increased leak conductance, which shunted tonic
      and burst firing. Isoflurane also blocked the low-threshold Ca(2+)-current
      underlying the burst mode of firing, by increasing leak current and depressing
      membrane Ca(2+)-channel activity. We suggest that the mechanism of anaesthesia is
      distinct from sleep, although both states critically involve excitabilities of
      thalamic neurons.

PMID- 8264988
TI  - Segregation of cerebrorubral and cerebellorubral synaptic inputs on rubrospinal
      neurons of fetal cats as demonstrated by intracellular recording.
AB  - Cerebrorubral and cerebellorubral inputs are localized to distal dendrites and
      somata of red nucleus neurons in adult cats, respectively. To examine if this
      segregation is established early in development, we performed intracellular
      recording from rubrospinal neurons of fetal cats aged from embryonic day 58 to
      65. Stimulation of the contralateral cerebellar nuclei evoked excitatory
      postsynaptic potentials (EPSPs). EPSPs were also induced by stimulation of the
      ipsilateral pericruciate cortext but they were much slower in time course and
      smaller in amplitude compared to cerebellar ones. We suggest that cerebrorubral
      and cerebellorubral synapses are segregated on soma-dendritic membrane of
      rubrospinal neurons early in development.

PMID- 8264989
TI  - Distribution and possible roles of the highly polysialylated neural cell adhesion
      molecule (NCAM-H) in the developing and adult central nervous system.
AB  - The neural cell adhesion molecule (NCAM) is a cell surface glycoprotein which is
      thought to mediate cell adhesion and recognition. During developmental stages,
      NCAM is highly polysialylated (NCAM-H) by a unique alpha-2,8-linked polysialic
      acid chain (PSA), and this PSA portion of NCAM-H has been found to be closely
      associated with various developmental processes of the nervous system. Further,
      recent immunohistochemical investigations have revealed that even in the adult
      nervous system, a persistent PSA expression has been found confined to several
      regions: the olfactory bulb, the piriform cortex, the hippocampal dentate gyrus,
      the hypothalamus, some nuclei of the medulla and the dorsal horn of the spinal
      cord, which are related directly or indirectly to sensory systems. Moreover, in
      the dentate gyrus and olfactory bulb the expression is connected with adult
      neurogenesis that may add new neuronal circuits to the adult neural tissue.
      Therefore, the possible role of NCAM-H in the central nervous system may be
      associated not only with neural development, but also with adult functions, such
      as the processing system of sensory information and neuronal plasticity.

PMID- 8264990
TI  - Hippocalcin: a calcium-binding protein of the EF-hand superfamily dominantly
      expressed in the hippocampus.
AB  - Hippocalcin is a recently identified Ca(2+)-binding protein with three EF-hand
      structures, dominantly expressed in the hippocampal pyramidal layer. The complete
      amino acid sequence of hippocalcin deduced from the cDNA is composed of 195
      residues, has a calculated molecular mass of 22,574 daltons, and has a striking
      sequence homology to those of visinin, recoverin, S-modulin, neurocalcins and
      neural visinin-like proteins. Hippocalcin binds 3 mol of Ca2+ per mol of protein
      at submicromolar Ca2+ levels, and associates the plasma membrane in a Ca(2+)
      dependent manner. Hippocalcin is myristoylated at its NH2-terminal glycine
      residue, and this modification is a key event in terms of its membrane
      association property.

PMID- 8264991
TI  - Responses of floccular Purkinje cells to sinusoidal vertical rotation and effects
      of muscimol infusion into the flocculus in alert cats.
AB  - To understand how the flocculus is involved in the integration process in the
      vertical VOR, we examined the responses of floccular Purkinje cells during whole
      body rotation in many vertical and horizontal planes in alert cats. The great
      majority of cells that responded to pitch rotation received excitation from the
      contralateral posterior canal, whereas the minority received excitation from the
      anterior canal, either on the ipsilateral or contralateral side; 35% of these
      vertical canal responding cells received convergent inputs, either from the
      ipsilateral or contralateral horizontal canal. After infusion of a GABA agonist
      (muscimol) into the area where many posterior canal responding Purkinje cells
      were recorded, the downward VOR induced by nose-up pitch was selectively impaired
      at low stimulus frequencies, together with an impairment of gaze holding after
      downward saccades. These results indicate a crucial role for posterior canal
      responding floccular Purkinje cells in generating downward eye position signals.
      Since the flocculus inhibits VOR interneurons related to the anterior and
      horizontal canals but not the posterior canal (Ito, 1984), our results suggest
      the possibility that posterior canal responding floccular Purkinje cells may form
      a transfloccular inhibitory pathway to anterior canal related VOR interneurons.
      This pathway may facilitate the positive feedback effect in the vestibular
      commissural inhibitory pathway between the co-planar vertical canals for the
      posterior canal signal, and may thereby be specifically involved in integration
      in the vertical VOR.

PMID- 8264992
TI  - The sites of origin of serotoninergic afferent fibers in the trigeminal motor,
      facial, and hypoglossal nuclei in the rat.
AB  - The sites of origin of serotoninergic afferents in the trigeminal motor (Vm),
      facial (VII), and hypoglossal nuclei (XII) were studied in the rat by fluorescent
      retrograde labeling with Fluoro-Gold, in combination with immunofluorescence
      histochemistry for serotonin (5-HT). The results indicated: (1) The nucleus raphe
      magnus, nucleus raphe pallidus, and nucleus raphe obscurus contained 5-HT neurons
      projecting to the Vm, VII or XII. (2) The nucleus raphe dorsalis sends 5-HT
      fibres to the Vm and VII, but not to the XII. (3) The gigantocellular reticular
      nucleus pars alpha contained 5-HT neurons projecting to the VII.

PMID- 8264993
TI  - Direct projection from the nucleus of the optic tract to the medial vestibular
      nucleus in the cat.
AB  - The nucleus of the optic tract (NOT) serves as an important visuo-motor relay
      between the retina and preoculomotor structures that mediate optokinetic
      nystagmus. In the present study, the efferent targets of NOT were investigated
      using biocytin as an anterograde tracer. Following biocytin injections into NOT,
      labeled fibers were observed in each of the following efferent pathways: (1)
      those that project to the contralateral NOT via the posterior commissure; (2)
      those that course through the nucleus reticularis pontis oralis to terminate in
      the nucleus reticularis tegmenti pontis; and (3) those that descend via the
      medial lemniscus to the level of the medulla to terminate in the dorsolateral
      pontine nucleus, nucleus prepositus hypoglossi, medial vestibular nucleus and the
      inferior olive. Direct projections from the NOT to the medial vestibular nucleus
      may contribute to the residual optokinetic responses of the vestibular nucleus
      neurons following cerebellar or inferior olivary lesions.

PMID- 8264994
TI  - Helping the dyslexic nursing student.
AB  - Some nursing students who are struggling to succeed academically may be dyslexic
      and may need help from nurse educators. First, the author describes ways to
      identify the student with dyslexia in both the clinical and classroom setting.
      Secondly, diagnostic processes are reviewed. Finally, the author discusses simple
      strategies that modify the learning environment while helping to foster student
      success.

PMID- 8264996
TI  - Teaching the use of data resources.
AB  - Reading a client's medical record is a skill that can be taught to nursing
      students. This is an example of a self-paced module to familiarize students with
      their textbook and reference books, with what is in the medical record, and with
      how the nurse uses the medical record.

PMID- 8264995
TI  - Dismissal for clinical deficiencies.
AB  - Students may challenge decisions of academic dismissal through local grievance
      procedures and the court system. When public safety and security are at issue,
      however, nursing faculty have the responsibility of dismissing students based on
      clinical performance. When due process is adequately served and students' civil
      rights protected, the courts have repeatedly upheld decisions made by higher
      education faculty and grievance committees. The author discusses several
      precedent-setting cases.

PMID- 8264997
TI  - Let's make baccalaureate education interesting for RNs.

PMID- 8264998
TI  - Community health service programs in academe: unique learning opportunities for
      students.
AB  - Services provided by a college of nursing allow students to participate in unique
      clinical experiences in nurse-managed healthcare. The authors describe the use of
      a nursing center, wellness program, and home health program of a college of
      nursing to provide clinical experiences for nursing students.

PMID- 8264999
TI  - AIDS-related stigma and homophobia: implications for nursing education.
AB  - Healthcare workers' attitudes about acquired immune deficiency syndrome (AIDS)
      are influenced by two major types of fears: AIDS-related stigma refers to
      irrational fears about contracting the virus and about death and dying issues,
      whereas homophobia refers to irrational fears or negative attitudes about same
      sex sexual behaviors or relationships. In this study, open-ended responses of
      nursing students to a videotape about an AIDS hospice were examined for the
      prevalence of these two types of fears. Most of the negative themes could be
      classified as AIDS-related stigma or homophobia. Implications for nursing
      education are discussed.

PMID- 8265000
TI  - Clinical application of undergraduate research skills: the Student Teams
      Utilizing Research (STUR) Project.
AB  - Although the desired outcome for undergraduate research curricula is to produce
      informed consumers/critiquers of research, baccalaureate students often have
      difficulty linking research concepts with clinical practice. The authors describe
      an innovative approach to integrating research content with a clinical experience
      through use of student teams working with practicing nursing preceptors to
      identify and study research problems.

PMID- 8265001
TI  - The voice: a teaching tool.

PMID- 8265002
TI  - Write it up.

PMID- 8265004
TI  - Through a new lens: doctoral education in nursing.

PMID- 8265003
TI  - Health assessment in schools of nursing.

PMID- 8265005
TI  - Assignments to promote student library use.

PMID- 8265006
TI  - Meeting the challenge of clinical instruction in the 1990s.

PMID- 8265007
TI  - Conundrum game for nursing theorists Neuman, King, and Johnson.

PMID- 8265009
TI  - Giving your patient a sitz bath.

PMID- 8265008
TI  - Celebrate your personal philosophy of nursing education.

PMID- 8265011
TI  - Administering aerosol therapy.

PMID- 8265010
TI  - Preventing lymphedema, an unwelcome sequel to breast cancer.

PMID- 8265012
TI  - Improving your teaching skills.

PMID- 8265013
TI  - Physical assessment options: the choice is yours.

PMID- 8265014
TI  - Attempted suicide.

PMID- 8265015
TI  - Dressed for success: how moisture-retentive dressings promote healing.

PMID- 8265016
TI  - A Christmas for Maria.

PMID- 8265017
TI  - T.B. threat: taking it seriously.

PMID- 8265018
TI  - Pain relief from the start.

PMID- 8265019
TI  - New opportunities in gerontologic nursing.

PMID- 8265020
TI  - Closing the circle: meeting your patients' final needs.

PMID- 8265021
TI  - Close-up on mandible fracture.

PMID- 8265022
TI  - Comparing low-profile gastrostomy tubes.

PMID- 8265023
TI  - New drugs.

PMID- 8265024
TI  - Praise for hospice nurses.

PMID- 8265025
TI  - Saying the right thing.

PMID- 8265026
TI  - Lessons from nature.

PMID- 8265027
TI  - Help me make it through the night.

PMID- 8265028
TI  - Counseling nurses effectively.

PMID- 8265029
TI  - Katherine's journey.

PMID- 8265030
TI  - Preventing errors associated with P.C.A. pumps.

PMID- 8265031
TI  - How to administer a Z-track injection.

PMID- 8265032
TI  - Hepatitis B: on-the-job exposure?

PMID- 8265033
TI  - Recognizing thyroid crisis.

PMID- 8265035
TI  - How we make our mark on the world.

PMID- 8265034
TI  - Boosting the failing heart with inotropic drugs.

PMID- 8265036
TI  - When the doctor delay pain relief.

PMID- 8265037
TI  - Using blood glucose meters: what you and your patient need to know, Part II.

PMID- 8265038
TI  - Strengthen your life-support skills.

PMID- 8265039
TI  - Educating about S.T.D.s.

PMID- 8265040
TI  - Was Mrs. Jimenez bewitched or just a crazy old lady?

PMID- 8265041
TI  - Laying out a care plan for the elderly postoperative patient.

PMID- 8265042
TI  - Managing pericardial tamponade.

PMID- 8265043
TI  - Mrs. Marino's granddaughter.

PMID- 8265044
TI  - Self-test: acute care nursing.

PMID- 8265045
TI  - Myths & facts ... about hysterectomies.

PMID- 8265046
TI  - Critical appraisal: risking to challenge.

PMID- 8265047
TI  - "Let's get rid of all nursing theory".

PMID- 8265048
TI  - Researching the lived experience: visions of the whole experience.

PMID- 8265049
TI  - Nursing theory-based practice and the Patient Self-Determination Act.

PMID- 8265050
TI  - The role of theory in qualitative research.
AB  - Increasingly philosophers and scientists have affirmed that all knowledge is
      theory-laden and that methods are theory-driven. These assertions raise important
      questions related to the role of theory in qualitative research. There are
      scholars who propose that qualitative research can enhance understanding and
      expand theoretical knowledge from a disciplinary perspective. And there are
      others who contend that qualitative inquiry is purely inductive and that its
      validity can therefore be judged by the extent to which preconceived theory is
      absent from it. The purpose of this article is to examine three qualitative
      methods, grounded theory, ethnography, and phenomenology, and their use in
      nursing in order to explicate the role of theory in knowledge development. The
      authors propose that, by nature, inquiry, discovery, and theoretical
      interpretation coexist simultaneously and must be recognized as such if the
      theory-research linkage is to advance nursing science through qualitative
      research.

PMID- 8265051
TI  - The science of unitary human beings: an integrative review.
AB  - This article is an integrative review of the research which has been carried out
      based on Martha Rogers' conceptual framework, the science of unitary, irreducible
      human beings. Results of the review supported the model and theories which have
      been derived from the framework. However, because of methodological difficulties
      in measuring the concepts and because of the instruments being used, this support
      is not statistically significant. More research is needed using methods and
      instruments which better fit the concepts that are basic to the Rogerian
      principles of homeodynamics. Also, theories being used as the basis of the study
      need to be more definitively stated in future research.

PMID- 8265052
TI  - Aging in the oldest old living in Scotland: a phenomenological study.
AB  - The purpose of this phenomenological study was to uncover ways in which the
      oldest old living in a Scottish community view the experience of aging. The
      research was guided by Parse's theory and followed the van Kaam method to elicit
      a structural definition of the meaning of aging, as described by the oldest old.
      Through the processes of intuiting, analyzing, and describing, it was found that
      the experience of aging is intensifying engagements as transfigurations signify
      maturity tempering the unavoidable with buoyant serenity. Findings are discussed
      in light of meaning specified in other explorations of the aging experience.
      Conceptual expansion enhances understanding for practice and further research.

PMID- 8265053
TI  - Neuman's framework and ventilator dependency: a pilot study.
AB  - The purpose of this article is to illustrate how the Neuman systems model guided
      a pilot study with ventilator-dependent patients. Mechanical ventilation was the
      external stressor to which these subjects reacted. The interaction of Neuman's
      client system variables was investigated to see which variables most influenced
      the weaning process. The pilot served to link model concepts with research
      variables and to identify appropriate procedures and tools for data collection.

PMID- 8265054
TI  - Unitary knowing in nursing practice.
AB  - The purpose of this article is to elaborate the unitary knowing perspective which
      was derived from using the science of unitary human beings in practice and
      considering phenomena within a unitary picture of reality. The systems
      perspective and the unitary perspective are contrasted as structures for
      understanding human phenomena in the realm of practice. A model of practice is
      offered which encompasses the use of experience, perceptions, and expressions as
      the source of pattern information. The features of unitary knowing involving
      construction and derivation are presented within the context of unitary pattern
      nursing.

PMID- 8265055
TI  - All I do is witness consent ...

PMID- 8265056
TI  - Should boards recognize education?

PMID- 8265057
TI  - Why nurses lose their licenses--Part III.

PMID- 8265058
TI  - Doing the right thing.

PMID- 8265059
TI  - Shifting perceptions: defining nursing informatics as a clinical specialty.

PMID- 8265060
TI  - Needed now: a junkyard dog!

PMID- 8265061
TI  - Capturing the activity factor: impact on volume.
AB  - In addition to Patient Classification System's information, nurse managers can
      use activity tools to develop and justify budget needs. A basic accounting-type
      workflow analysis format, which goes beyond the "Midnight Census," accurately
      details a unit's patient volume and productive hours.

PMID- 8265062
TI  - AMA's policies and nursing's role in emerging systems.
AB  - As nursing rises to meet the challenges of change, it is increasingly important
      to present the claims of nursing in terms that are morally and scientifically
      accountable. The challenge to balance the interests of the professions with the
      interests of patients will continue as healthcare issues are determined.

PMID- 8265063
TI  - Politics and the nurse manager.
AB  - Sometimes, the "games being played" in our job settings cripple our ability to be
      powerful, effective participants in the world of work. Power, which is the
      ability to obtain, retain and move resources, requires two sets of attributes:
      competence and political savoir-faire. Much attention is given to improving
      competence but little time is spent in learning the intricacies of political
      behavior. The most important strategy is to learn to "read the environment"
      through observation, listening, reading, detachment and analysis.

PMID- 8265064
TI  - A cost allocation model for hospice.
AB  - Increasingly, nurses are becoming involved in the financial aspects of healthcare
      delivery to determine cost-effectiveness of nursing product lines. A model
      allocating costs for 15 service components was developed using data from 52
      patients receiving Medicare hospice benefits in a home care environment. The
      model may be adapted for any service line with multiple components and providers
      to allocate patient care costs.

PMID- 8265065
TI  - High-volume obstetrics in a combined LDR/LDRP program.
AB  - A combined LDR/LDRP unit works well for high-volume obstetrical service. It
      allows for diverse staff clinical expertise and a strong team identity in
      providing a comprehensive obstetric service. It offers managers increased
      flexibility in managing costs and an ongoing opportunity to mentor and role model
      collegiality. It gives consumers a choice of service to meet specific needs.

PMID- 8265066
TI  - Collaborative teaching: preparing for the reality of nursing.
AB  - Together, a local healthcare agency and the baccalaureate faculty at a Midwestern
      university designed a management course that uses a collaborative clinical
      teaching model. The teaching method gives the senior nursing student an
      opportunity to learn the leader/manager/coordinator role. As a result, students
      are better prepared to make professional judgments and care for large groups of
      clients in acute healthcare settings.

PMID- 8265067
TI  - Point-of-care testing: improving day-stay services.
AB  - To run an effective Day-Stay program, objectives must be focused and patient care
      must be accurate, tightly controlled, time-efficient and cost-effective.
      Obtaining critical blood test results immediately at the patient's side, a point
      of-care technology, can improve overall Day-Stay unit operations and patient
      service.

PMID- 8265068
TI  - Trauma nurse coordinator: three unique roles.
AB  - Three nursing positions were created to effectively manage the Trauma Nurse
      Coordinator (TNC) role and responsibilities: Trauma Director, Clinical Nurse
      Specialist and Trauma Researcher. By using this innovative approach, the quality
      of trauma care improved as shown by decreased complication rates, lengths of
      stay, and trauma costs. In addition, trauma referrals, research and education
      increased.

PMID- 8265069
TI  - Barbarians at the gate.

PMID- 8265070
TI  - When a triad is needed.

PMID- 8265071
TI  - A teaching day strategy.

PMID- 8265072
TI  - Recruiting the novice: a medical nursing internship program.

PMID- 8265073
TI  - Nurses link up to high-speed communication network.

PMID- 8265075
TI  - In celebration of nurse managers. American Organization of Nurse Executives.

PMID- 8265074
TI  - Liability for drug testing.

PMID- 8265076
TI  - Client/server technology: a new way to manage information.

PMID- 8265077
TI  - Damage control and the whistleblower.

PMID- 8265078
TI  - Leadership behavior and employee effectiveness.
AB  - A research study shows how leaders can significantly impact employee
      productivity, job satisfaction and commitment. Five leadership skills basic to
      good management are developed and implemented to complement the nurse manager's
      own unique style. Employees, in turn, will respond to the manager's examples of
      high standards and values.

PMID- 8265079
TI  - Assessing co-dependency issues within a nursing environment.
AB  - An exploratory study, using the Friel Co-dependence Assessment Inventory, and the
      four modes in Roy's adaptation model examined levels of co-dependency in nurses.
      Empirical data bases are provided for future studies. Using Roy's adaptation
      model, co-dependency studies can be done on the levels of stimuli (focal,
      contextual, and residual) confronting the nurses' adaptive systems in the work
      environment.

PMID- 8265080
TI  - The Myers-Briggs type indicator--a management tool.
AB  - The Myers-Briggs Type Indicator can be an enlightening experience for managers as
      it uncovers blind spots as well as provides insight into managerial styles. This
      tool offers a way to build communication patterns that meet nurse managers' needs
      and the needs of the people they supervise.

PMID- 8265081
TI  - Collegial support linked to reduction of job stress.
AB  - A study examining the relationship between staff nurses' perceptions of collegial
      support and job stressors reveal the importance of supportive relationships
      within the work environment. Identifying and reinforcing effective coping
      mechanisms and developing supportive relationships can enable a staff nurse to
      provide safe nursing care.

PMID- 8265082
TI  - Learning from success: autonomy and empowerment.
AB  - Evidence of autonomous, empowered behavior among nursing personnel at all levels
      is one of the critical factors looked for by teams reviewing a hospital for
      magnet hospital status. The kind of culture and leadership strategies which can
      ensure an atmosphere necessary to facilitate such behavior are described as they
      exist at a suburban community hospital which has achieved this distinction most
      recently.

PMID- 8265083
TI  - Gender gaps within management.
AB  - Traditional roles need not become self-fulfilling prophecies if managers can
      bridge the gender gap. Feminine, as well as masculine, characteristics can be
      incorporated into managerial styles to enhance effective leadership. Autonomy,
      decision-making and assertiveness are as important as nurturing and caring. What
      are little girls made of? Little girls are made of sugar and spice and everything
      nice. What are little boys made of? Little boys are made of rats and snails and
      puppy dog tails.

PMID- 8265084
TI  - Confrontation: methods and skills.
AB  - By identifying personal "hot buttons," nurse managers gain insight into the
      reasons they avoid problems or use inappropriate confrontation techniques.
      Through appropriate guidelines, successful confrontation can resolve conflicts
      and improve communication.

PMID- 8265085
TI  - People make the place.

PMID- 8265086
TI  - Collaborative practice: a shared success.
AB  - A community hospital reflects on changes made when implementing a collaborative
      practice theory. Using a philosophy that called both professional groups to
      "share and work together to provide thorough and consistent patient care," a
      successful joint practice was operational within a year.

PMID- 8265087
TI  - Surviving verbal abuse: a win-win game plan.
AB  - Verbal abuse, one of many tactics used when communication breaks down,
      aggressively manipulates others into competitive power struggles loaded with
      hidden agendas. A specific win-win game plan is given to survive these verbal
      abuse tactics.

PMID- 8265088
TI  - When nurses strike: ethical conflicts.
AB  - Quotes from physicians and Health Ministry officials during the 1986 Israeli
      nurses' strike vividly describe a critical patient and hospital scenario. In
      turn, nurses involved discounted the charges as "psychological scare tactics."
      Comments from the Israeli healthcare members and government officials outline the
      effects, the content, and the ethical issues of the strike.

PMID- 8265089
TI  - Facilitating inservice programs through PERT/CPM. Project Evaluation and Review
      Technique/Critical Path Method.
AB  - Project Evaluation and Review Technique (PERT) and the Critical Path Method (CPM)
      are used primarily in industrial settings to manage the efficiency and cost
      effectiveness of projects. Simultaneous use of these approaches can be applied to
      planning nursing inservice programs, seminars and workshops.

PMID- 8265090
TI  - Competency-based orientation in pediatric critical care.
AB  - Having recognized the need to update and modify their orientation program, a PICU
      nursing management team decided to develop a competency-based program. The goal
      was to facilitate transition of an orientee into a competent entry-level
      practitioner. This article outlines the procedure used to develop the initial
      phases: lists of competencies, competency evaluation worksheet and performance
      checklists. Later, various learning options and additional evaluation methods
      will be explored.

PMID- 8265091
TI  - Leadership: moving into the twenty-first century.
AB  - Leadership and management affect business, political and societal ventures as
      well as healthcare organizations. By studying the traits and qualities of these
      key positions, nurses can analyze potential leaders and expand their roles as
      they move into the 21st century.

PMID- 8265092
TI  - Patient outcomes measure home health care accomplishments.
AB  - Professional, governmental, and economic stakeholders are calling for more
      explicit accountability for consistent quality from home health-care agencies. A
      system oriented toward outcomes for the patient rather than toward service design
      and distribution is more likely to improve the quality of care and satisfy
      everyone involved.

PMID- 8265093
TI  - Treatment of gastric adenocarcinoma with the combination of etoposide, adriamycin
      and cisplatin (EAP): comparison between two schedules.
AB  - The results of two schedules of the combination of etoposide, doxorubicin, and
      cisplatin (EAP) in gastric cancer are reported. EAP-1 was administered as
      originally reported and consisted of i.v. doxorubicin (adriamycin) 20 mg/m2 on
      days 1 and 7, i.v. cisplatin 40 mg/m2 on days 2 and 8 and i.v. etoposide (VP-16)
      120 mg/m2 (100 mg/m2 in patients aged 60-65) on days 4-6. EAP-2 consisted of i.v.
      adriamycin 40 mg/m2 on day 1, i.v. cisplatin 80 mg/m2 (total dose per cycle)
      given in 3 divided doses on days 1-3 and i.v. VP-16 100 mg/m2 on days 1-3. Cycles
      of the two regimens were repeated on day 22. Drug doses were reduced in patients
      over 65 years of age. Twenty patients were treated with EAP-1 and 43 with EAP-2.
      Forty-five of the 63 patients included in this study had advanced gastric
      carcinoma, 16 had radically resected stage III disease, and 2 had metastatic
      signet ring cell carcinoma of unknown primary origin. Thirty-eight patients with
      advanced gastric adenocarcinoma were evaluable for response. The response rate
      for EAP-1 (6/13, 46%) was similar to that of EAP-2 (13/25, 52%). The median
      duration of response was 8 months for EAP-1 and 6.5 months for EAP-2.
      Myelotoxicity of EAP-1 was much more severe than that of EAP-2. Hospitalization
      due to granulocytopenic fever was required in 15/78 (19%) EAP-1 versus 20/215
      (9%) EAP-2 courses. Toxic deaths occurred in 3/20 treated with EAP-1 and in 1/45
      treated with EAP-2. The difference in toxicity between the two regimens could not
      be attributed to differences in patients' characteristics or to dose intensity.
      We conclude that the modified EAP regimen (EAP-2) is effective in the treatment
      of gastric cancer and is less toxic than the original EAP.

PMID- 8265094
TI  - Azaphilones inhibit tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in
      two-stage carcinogenesis in mice.
AB  - Monascorubrin (an azaphilone derivative) was isolated from Monascus anka,
      'Monascus pigment', a natural pigment of food additivies, was extracted from
      Monasucs spp., and chaetoviridin A, one of the azaphilones, was isolated from
      Chaetomium globosum var. flavo-viridae. Application of 1 microgram of 12-O
      tetradecanoylphorbol-13-acetate (TPA), a tumor promoting agent, to the mouse ear
      resulted in induction of inflammation. Among monascorubrin and related compounds
      assayed, monascorubrin, chaetoviridin A and its related compounds inhibited the
      inflammatory activity of TPA in mice. The 50% inhibitory dose of these compounds
      for TPA-induced inflammation was 0.4-1.5 mumol. Furthermore, monascorubrin (2
      mumol), chaetoviridin A (2 mumol) and Monascus pigment (1 mg) markedly suppressed
      the promoting effect of TPA (1 microgram) on skin tumor formation in mice
      initiated with 7,12-dimethylbenz[a]anthracene (50 micrograms). It is assumed that
      the inhibition of tumor promotion by monascorubrin, chaetoviridin A and Monascus
      pigment is due to anti-inflammatory activity.

PMID- 8265095
TI  - Ondansetron compared with granisetron in the prophylaxis of cisplatin-induced
      acute emesis: a multicentre double-blind, randomised, parallel-group study. The
      Ondansetron and Granisetron Emesis Study Group.
AB  - This is the first international, multi-centre, double-blind, randomised, parallel
      group study to directly compare the efficacy and safety profile of a single
      intravenous dose of ondansetron (8 or 32 mg) with granisetron (3 mg) in the
      control of cisplatin-induced acute emesis. A total of 496 patients were
      randomised to receive one of three anti-emetic treatments prior to cisplatin
      chemotherapy (> or = 50 mg/m2). Of these, 165 and 162 patients received 8 and 32
      mg of ondansetron, respectively, and 169 patients received 3 mg of granisetron.
      Complete control of emesis (0 emetic episodes) over 24 h was reported in 59% of
      patients in the 8-mg ondansetron group, 51% of patients in the 32-mg ondansetron
      group and 56% of patients in the granisetron group. Complete or major control (<
      or = 2 emetic episodes) was achieved in 76 and 74% of patients in the 8- and 32
      mg ondansetron group, respectively, compared with 78% of patients in the
      granisetron group. Nausea graded none or mild 24 h after the start of cisplatin
      infusion was reported in 71 and 69% of patients in the 8- and 32-mg ondansetron
      groups, respectively, and in 73% of patients in the granisetron group. There were
      no significant differences between the treatment groups when global satisfaction
      scores were compared. Logistic regression models were fitted to assess any
      interaction between treatments and prognostic factors (age, gender, alcohol use,
      cisplatin dose or concomitant chemotherapy) on complete or major response, but
      there was no evidence of interaction for any factor. All three anti-emetic
      treatments were well tolerated and no severe or unexpected drug-related adverse
      events were observed with ondansetron or granisetron. Headache, the most reported
      drug-related adverse event for all three treatment groups, occurred in 9% of all
      patients. In summary, no significant difference was observed between any of the
      treatment groups with respect to emesis, nausea or drug-related adverse events.

PMID- 8265096
TI  - Amplification of the c-myc proto-oncogene in soft tissue sarcomas.
AB  - Soft tissue sarcoma fresh specimens from 23 patients were screened for genetic
      abnormalities of 3 cellular oncogenes, i.e., c-myc and c-myb and c-Ha-ras.
      Southern blot hybridization analysis demonstrated amplification of the c-myc gene
      (4- to 8-fold) in 7 cases, i.e., 3 malignant fibrous histiocytomas, 1
      liposarcoma, 1 fibrosarcoma, 1 lymphoma of the soft tissues and 1 synovial
      sarcoma. Amplification of the c-myc gene was not associated to other genetic
      alterations such as gene rearrangement. Hybridizations with c-myb and c-Ha-ras
      probes showed no gene abnormalities in this series. Our results indicate that c
      myc oncogene amplification may play an important role in the development of
      certain soft tissue sarcomas as it has been found for other human malignancies.
      The clinical significance of these features remains to be established.

PMID- 8265097
TI  - Circulating CA 549 and other associated antigens in breast cancer patients.
AB  - The new marker CA 549 was determined in the serum of 258 breast cancer patients,
      classified according to TNM (148 at diagnosis and 110 at relapse), using a RIA
      method (cut-off: 10 U/ml). CEA, CA 15-3 and MCA were also evaluated. At
      diagnosis, CA 549 was more sensitive than the other markers, and cut-off values
      of 11 and 12 U/ml did not significantly reduce sensitivity. No significant
      correlation existed between the markers, except for CA 15-3 and CA 549 (r =
      0.65). A new quantitative approach to the four markers was effected in the
      relapsed patients: an X value was calculated for each marker by dividing serum
      concentration by its cut-off. In these patients, grouped according to the area
      involved, marker sensitivities were similar except in locoregional relapse, where
      CA 549 and MCA were the most sensitive. From the data obtained, the more defined
      cut-off and the good specificity, it is suggested that CA 549 be routinely
      determined in the follow-up of the disease.

PMID- 8265098
TI  - Prognostic factors in anal carcinoma.
AB  - This study was performed to examine if commonly recorded parameters are of
      prognostic importance for patients with squamous cell carcinoma of the anal
      canal. A total of 77 patients received combined chemoradiotherapy and were
      followed at regular intervals after treatment. Age, sex, performance status,
      tumour stage, histopathological differentiation and grade, were not found to be
      of prognostic importance. Most blood tests did not correlate with prognosis,
      although elevated serum alkaline phosphatase (ALP) and lactate dehydrogenase (LD)
      proved to be unfavourable prognostic factors. In the present study serum ALP and
      LD were the only parameters that significantly correlated with development of
      distant metastases during follow-up.

PMID- 8265099
TI  - Changes in tissue levels of glutathione, extent of lipid peroxidation, and
      activity of glutathione peroxidase in transplantable murine lymphoma.
AB  - The reduced glutathione (GSH) levels in the hepatic tissues, extent of lipid
      peroxidation in the liver, kidney and brain, and alterations in the activity of
      glutathione peroxidase (GPX) in the hepatic tissues were monitored in mice
      bearing a transplantable ascitic lymphoma. These markers showed substantial
      alterations during the height of tumour progression when compared to controls.
      The GSH level, extent of lipid peroxidation, and GPX activity increased sharply
      after approximately 2 weeks following inoculation of ascitic cells. This was
      followed by a steady decline in all markers and death occurred around day 32
      after inoculation.

PMID- 8265100
TI  - Primary mucinous adenocarcinomas and signet-ring cell carcinomas of colon and
      rectum.
AB  - Of 352 patients with colorectal carcinoma followed for a minimum of 5 years after
      surgery, 39 cases (11.1%; median age 60 years) had mucinous adenocarcinoma, and 4
      (1.1%; median age 62 years) had signet-ring cell carcinoma. Mucinous carcinomas
      were most frequently located in the rectum (61.5%) and in the sigmoid colon
      (15.3%) and presented with stage C and D disease in 41 and 15% of the cases,
      respectively. Disease recurrence was more frequently observed in patients with
      mucinous (51.7%) or signet-ring lesions (100%) as compared with adenocarcinomas.
      Five-year survival was 45 (median 48 months), 28 (median 27), and 0% (median 15
      months) in patients with adenocarcinomas, mucinous adenocarcinomas, and signet
      ring cell carcinomas, respectively (p < 0.05). Mucinous carcinomas of the rectum
      had had a significantly worse prognosis (5-year survival 17%, median 33 months)
      as compared with adenocarcinomas of the same site (5-year survival 34%, median 25
      months; p < 0.05).

PMID- 8265101
TI  - Growth characteristics of nonmalignant cells in the ATP cell viability assay.
AB  - Over the last 5 years, the ATP cell viability assay (ATP-CVA) has been used to
      study the in vitro response of cell lines and fresh gynecologic human tumors to a
      variety of antineoplastic agents including chemotherapeutic agents, hormones and
      biological response modifiers. This assay measures light production as
      intracellular ATP interacts with the luciferin-luciferase complex. Quantitation
      of the light produced has been shown to directly correspond with the number of
      viable cells. A past criticism is that in the ATP-CVA, when applied to fresh
      tumor tissue, normal cells (fibroblasts, macrophages and lymphocytes) also
      produce ATP, and if present in sufficient numbers, could lead to errors in
      chemosensitivity testing results. This study was designed to evaluate the growth
      characteristics of various benign cells found in fresh tumors. The cells were
      studied under multiple plating conditions to show the relative increase or
      decrease of fractional ATP measured at different time points. We found that
      agar/McCoy underlayer and agarose-coated wells do not permit the growth of
      nonmalignant cells. In the culture conditions of the ATP-CVA, non-malignant cells
      do not contribute relevant ATP levels when treated samples are compared to
      controls on day 6. Therefore, results of the ATP-CVA in fresh tumors should not
      be affected.

PMID- 8265102
TI  - Evaluation of skull base erosion in nasopharyngeal carcinoma: comparison of plain
      radiography and computed tomography.
AB  - Over a period of 16 months, a total of 175 patients with newly diagnosed
      nasopharyngeal carcinoma (NPC) were evaluated with plain radiography and computed
      tomography (CT) of nasopharynx and base of skull. 54 of 175 patients (30.9%) had
      CT evidence of skull base erosion. Plain radiography failed to demonstrate the
      skull base erosion in 22 of 54 patients (40.7%) and underestimated the extent of
      bony involvement in another 21 patients (38.9%). In 14 of 54 patients (25.9%),
      there was also false suspicion of bony erosion in the plain films in one or more
      regions of the skull base which was not substantiated by CT and subsequent
      clinical course. The present study shows that plain radiography lacks sensitivity
      and specificity in detecting skull base erosion by NPC. CT evaluation of NPC
      patients should include thin CT sections of base of skull for detection of subtle
      bone erosion, and this would allow better decision concerning the shielding of
      the pituitary-hypothalamic axis during radiotherapy for improvement in
      therapeutic ratio. For the investigation of individuals highly suspicious of
      harboring NPC, even when the plain radiography is negative, CT should still be
      performed as this may give the only clue to the presence of a small submucosally
      spreading NPC.

PMID- 8265103
TI  - Positive correlation between cytochrome P450 2E1 mRNA level and serum estradiol
      level in human uterine endometrium.
AB  - Most carcinogens are bioactivated by cytochrome P450s (CYPs) and these enzymes
      within target cells are closely related to susceptibility to cancer. Since
      extrahepatic CYPs occur typically at much lower levels, the existence and the
      role of CYP in extrahepatic tissues have been difficult to assess. In this study,
      we modified the reverse transcriptase-polymerase chain reaction (RT-PCR) to
      evaluate the relative quantities of CYP 2E1 mRNA in human endometrium. Total RNA
      from human endometrium was reverse-transcribed and co-amplified by PCR in the
      same tube containing both primer pairs of CYP 2E1 and beta-actin. The CYP 2E1 and
      beta-actin PCR products were 298 and 600 bp, respectively. The restriction enzyme
      MboI digested these two products to the predicted size for DNA fragments,
      demonstrating that both PCR products were specific and CYP 2E1 mRNA exists in
      human endometrium. CYP 1A1 mRNA was also examined, but could not be detected
      clearly. Adding [alpha-32P]dCTP to the reaction mixture made it possible to
      quantify the relative yield of the CYP 2E1 PCR product in comparison with the
      beta-actin product. The ratio of the yield of the CYP 2E1 PCR product to the beta
      actin PCR product could be calculated at a point of 25 cycles of amplification.
      This ratio and serum estradiol levels were correlated positively (r = 0.654; p <
      0.05), but no relationship to serum progesterone levels was observed.

PMID- 8265104
TI  - Prognostic factors of the clinical response to subcutaneous immunotherapy with
      interleukin-2 alone in patients with metastatic renal cell carcinoma.
AB  - The intravenous immunotherapy with interleukin 2 (IL-2) represents one of the
      most active therapies of metastatic renal cell carcinoma (RCC). Recently, it has
      been demonstrated that IL-2 given subcutaneously in association with interferon
      alpha (IFN) may determine a response rate in RCC comparable to that obtained with
      an intravenous route of administration, but with a lower toxicity. Moreover, our
      previous data have suggested that IFN is not essential for IL-2 efficacy. On the
      basis of these data, we have designed a protocol of immunotherapy with IL-2 alone
      given subcutaneously in the treatment of metastatic RCC. The study included 48
      consecutive evaluable patients. IL-2 was given at a daily dose of 6 million IU
      for 5 days/week for 6 consecutive weeks, corresponding to one IL-2 cycle. The
      overall response rate was 14/48 (29%; CR:1; PR:13). Response rate was
      significantly higher in nephrectomized than in nonnephrectomized patients, and in
      patients with a good compared to those with a low performance status. Patients
      with an interval between the diagnosis of primary renal tumor and of its
      metastases longer than 1 year did better than those with a lower interval, as did
      patients with a single metastasis compared to those with multiple metastases,
      while no significant difference was seen in relation to sex, age and previous IFN
      therapy. As far as dominant metastasis sites are concerned, patients with liver
      metastases showed a response rate significantly lower than that seen in patients
      with metastases in sites other than liver. Toxicity was low in all patients. This
      study shows that the subcutaneous immunotherapy with IL-2 alone is a well
      tolerated and effective therapy of metastatic RCC. The evidence of a low PS,
      disseminated tumor and liver metastases represents the most important negative
      prognostic factor for the response to therapy.

PMID- 8265105
TI  - Endemic African Kaposi's sarcoma: clinical and therapeutic implications. 10-year
      experience in the Johannesburg Hospital (1980-1990).
AB  - Endemic African Kaposi's sarcoma is a common neoplastic disorder in the sub
      Saharan region of Africa. We present a retrospective analysis of 47 black
      patients with the endemic African (HIV-negative) variant of Kaposi's sarcoma
      treated and followed up in the Johannesburg General Hospital between 1980 and
      1990. Four patients (8%) presented with simultaneous Kaposi's sarcoma plus
      malignant lymphoma, indicating a low but significant association with
      lymphoproliferative disorders. Of 47 patients seen, 29 presented with localized
      disease and were treated by means of local radiation therapy. Seventeen patients
      received chemotherapy. The objective response rate was > 80% irrespective of the
      treatment modality. We conclude that endemic African Kaposi's sarcoma is a chemo-
      and radiosensitive tumour.

PMID- 8265106
TI  - Control of chemotherapy-induced diarrhea with octreotide. A randomized trial with
      placebo in patients receiving cisplatin.
AB  - Cisplatin-related diarrhea is a relatively common complication in the clinical
      management of cancer patients and until now no treatment for this condition has
      been identified. Octreotide has been reported effective in the treatment of 5
      fluorouracil-related diarrhea. To assess the safety and efficacy of octreotide in
      controlling diarrhea caused by cisplatin, 43 patients who had already had
      diarrhea during the 24-hour period following a previous cisplating administration
      were randomized to receive either octreotide or placebo during the next cisplatin
      course. The patients given octreotide experienced less diarrhea (5 vs. 75%, p =
      0.01). There were no side effects. We conclude that octreotide is more effective
      than placebo in controlling diarrhea following cisplatin chemotherapy.

PMID- 8265107
TI  - Comparison of current alkylating agents with a homo-aza-steroidal ester for
      antineoplastic activity.
AB  - The modified steroidal alkylating agent, 17 beta-hydroxy-3-aza-A-homo-4 alpha
      androsten-4-one-p-bis(2-chloroethyl)aminophenoxyacetate++ + has been tested
      against L1210 and P388 leukemias, and Lewis lung cancer, on DNA synthesis of EAT,
      L1210, P388, and BHK cell cultures, and on the induction of sister chromatid
      exchange. Comparable studies in vivo and in vitro were also done with p-bis(2
      chloroethyl)aminophenoxyacetic acid, cyclophosphamide, melphalan, and
      chlorambucil.

PMID- 8265108
TI  - High-dose (480 mg/day) tamoxifen with etoposide: a study of a potential multi
      drug resistance modulator.
AB  - Tamoxifen and its principle metabolite N-desmethyltamoxifen can modulate multi
      drug resistance in vitro. Tamoxifen 480 mg/day was given for 6 days with oral
      etoposide on days 4-6 to 17 patients with advanced solid tumours. Venous
      thrombosis (2 patients), reversible neurological toxicity (1 patient), and WHO
      grade III nausea/vomiting (3 patients) related to tamoxifen were observed but
      overall toxicity was manageable. One partial response occurred in 15 assessable
      patients. Mean plasma concentrations of tamoxifen and N-desmethyltamoxifen
      increased to 4.3 mumol/l and 2.7 mumol/l, respectively, by day 6. Plasma
      concentrations corresponding to active in vitro levels were attained by most
      patients.

PMID- 8265109
TI  - 13-cis-retinoic acid plus interferon-alpha: a phase II clinical study in squamous
      cell carcinoma of the lung and the head and neck.
AB  - Retinoids and interferon-alpha (IFN-alpha) have been shown to have a synergetic
      antiproliferative and differentiative effect on many cell lines, and in
      combination they have already been tested with some success in the treatment of
      some tumors. We investigated the tolerance and efficacy of high dose 13-cis
      retinoic acid (2 mg/kg/day) and IFN-alpha in the treatment of advanced squamous
      cell carcinoma of the lung and of the head and neck. No partial or complete
      response was observed in the 10 patients treated. The toxicity was unusual and
      mild to moderate considering the dose of retinoid given. This observation leads
      us to suspect that IFN-alpha may alleviate some of the side effects of the
      retinoid, and is of interest in the design of future clinical trials.

PMID- 8265110
TI  - Treatment of advanced primary lung cancer associated with malignant pleural
      effusion by the combination of immunotherapy and chemotherapy.
AB  - Twelve patients with advanced primary lung cancers associated with malignant
      pleural effusion were treated with intrathoracic instillation of recombinant
      interleukin-2 with or without in-vitro-sensitized cells. Two cases achieved
      complete response, and 7 partial response. The adverse effects seen in the
      protocol were marginal, and the protocol was well-tolerated and feasible.
      Furthermore, 4 cases were treated with the combination of systemic chemotherapy
      and adoptive immunotherapy. Of these, 3 cases responded well to the therapy and
      have shown a complete response for more than 20 months, indicating that adoptive
      immunotherapy together with chemotherapy might be a beneficial treatment for
      advanced lung cancer patients.

PMID- 8265111
TI  - Correlation of (S+G2)-phase fractions determined by flow cytometry and Ki-67
      labelling indices in colorectal carcinomas.
AB  - Samples from 14 human colorectal carcinomas were analysed by means of classical
      (one-parameter) flow cytometry. (S+G2)-phase fractions were calculated from DNA
      histograms with the help of two different algorithms. At the same time, the
      percentage of cells positive for the Ki-67 antibody, which recognizes
      proliferating cells, was determined in cytocentrifuge preparations. Significant
      correlations between the two indices were found only if the histogram analysis
      included background subtraction and aggregate correction. This finding may throw
      some light on the reliability of prognosis based on flow cytometry.

PMID- 8265112
TI  - Therapeutic and endocrine effects of Decapeptyl, synthetic LH-RH agonistic
      analogue in premenopausal women with metastatic breast cancer. A pilot phase II
      study.
AB  - Twelve premenopausal patients with advanced breast cancer were entered into pilot
      phase II study to assess efficacy, toxicity and influence of the synthetic LH-RH
      agonistic analogue D-Trp6-LH-RH (Decapeptyl) on the patients' hormonal status.
      The patients, aged 33-50, with newly diagnosed stage IV or recurrent breast
      cancer were not previously treated by any kind of endocrine therapy. Steroid
      receptor status was known in 9 patients. Decapeptyl was applied monthly at a dose
      of 3.75 mg i.m. until progression. The therapeutic response was evaluated in
      11/12 patients. Partial remission was achieved in 5, stabilization in 3, and 3
      consecutive patients failed to respond. The best therapeutic response was
      obtained in patients with pleuropulmonal and soft-tissue involvement, aged 41-45,
      including those with incomplete ovarian suppression, and regardless of steroid
      receptor status. The mean serum gonadotropins and estradiol levels were
      suppressed. The treatment was free of any side effects, except hot flushes in 7
      patients.

PMID- 8265113
TI  - Astrocyte cytoarchitecture in cochlear nuclei of the rat: an immunocytochemical
      study.
AB  - Astrocytes play important roles in the development, maintenance and function of
      neural circuits. We have studied the astrocytic cytoarchitecture of the adult rat
      cochlear nuclei using a monoclonal antibody against glial fibrillary acidic
      protein, a well-known intermediate filament of the cytoskeleton of the glial
      cells. The cochlear nuclear complex is the first central step in the ascending
      auditory pathway. The morphology and distribution of astrocytes, as well as the
      relationship of astroglial processes with neurons, have been found to be
      different in the three main subdivisions of the cochlear nuclei and could be
      related to their function.

PMID- 8265114
TI  - Synaptophysin immunoreactivity in the cochlear nuclei of mammals: a comparative
      study.
AB  - Synaptophysin is a Ca(2+)-binding glycoprotein located in the presynaptic
      membrane and synaptic vesicles. This glycoprotein has been also involved in the
      release of neurotransmitters. The presence of synaptophysin within the cochlear
      nuclear complex of several animal species was analyzed. Differences in size and
      neuronal density of the cochlear nuclei were observed between the animal species
      studied. In fact, cat and rat cochlear nuclei showed a very similar morphology
      and neuronal distribution, while mouse, hamster and guinea pig exhibited
      important differences. The morphology and arrangement of synaptic boutons, for
      each neuronal type considered, were similar among species.

PMID- 8265115
TI  - Piribedil could modify dopamine turnover in cochleas under noise stimulation.
AB  - Dopamine (DA) is one of the putative neurotransmitters of the lateral efferent
      olivocochlear fibers. The cochlear DA content after noise exposure was analyzed
      using high-performance liquid chromatography coupled with electrochemical
      detection. Animals were exposed for 1 h to white noise at 70, 90 or 110 dB SPL or
      were kept in conditions of silence. Half of the animals were pretreated with
      piribedil, a D2 agonist, and the other half served as controls. In control
      (untreated) animals, noise stimulation resulted in a progressive decrease of
      cochlear DA concentration. This decrease was scarcely detected when animals were
      pretreated with piribedil. Present findings indicate that piribedil modifies
      cochlear DA turnover under noise stimulation.

PMID- 8265116
TI  - Regeneration of adult budgerigar's hair cells following acoustic trauma.
AB  - The functional and structural changes of hair cells of the adult budgerigar
      following acoustic trauma were examined using auditory brainstem response (ABR),
      and both scanning and transmission electron microscopy. Just after exposure to a
      1,500-Hz pure tone at 120 dBSPL for 98 h, severe damages and disappearance of
      short hair cells were observed in the middle region of the basilar papilla.
      Fourteen days after the exposure, the threshold of ABR recovered to the level
      before the exposure, and normal short hair cells, which have synapses with nerve
      endings, were rearranged all over the damaged region of the basilar papilla.
      These results indicate that the hair cells of the adult budgerigar have
      capability to regenerate, and to restore the auditory perceptive function
      following acoustic trauma.

PMID- 8265117
TI  - Effects of high-frequency sound on the guinea pig cochlea. Electrophysiological
      study using cochlear microphonics, action and endocochlear potential.
AB  - There are only a few studies investigating the effect of high-frequency sound on
      hearing. Authors investigated experimentally the effect of long exposure to high
      frequency sound (19 and 25 kHz) below 100 dB (SPL) on guinea pig inner ear.
      Changes in cochlear microphonics (decrease of maximum output voltage) and
      especially in endocochlear potential (decrease of the absolute value of negative
      potential) were observed. The effects of high-frequency sound (10-30 kHz) on the
      inner ear were discussed.

PMID- 8265118
TI  - Early morphofunctional alterations induced by cisplatin in the cochlea. A
      quantitative and electrocochleographic study.
AB  - The early morphological and functional alterations of the cochlea were studied in
      guinea pigs treated with cisplatin, administered to two groups of animals as a
      single dose of 4 or 10 mg/kg body weight. Morphological changes were observed by
      scanning electron microscopy, and functional alterations were investigated by
      electrocochleography to record compound action potentials. Statistically
      significant alterations in neurosensory stereocilia, consisting of partial or
      total denudation, were observed only after the experimental administration of the
      higher dose of cisplatin; these changes were consistently associated with
      distortions in the compound action potential.

PMID- 8265119
TI  - Vowel and consonant identification tests can be used to compare performances in a
      multilingual group of cochlear implant patients.
AB  - Vowel and consonant identification tests were conducted in the sound-only
      condition in a multilingual group of 13 totally deaf patients who are users of
      the Ineraid multichannel cochlear implant. Native languages ranged across French,
      German, Italian, Spanish, Albanian and Swahili. We found high correlations (r > 
      0.83) among vowel or consonant identification scores and 'subjective ranking'
      scores established on the basis of a subjective evaluation of the patient's
      speech reception abilities in the sound-only condition. Detailed analysis
      demonstrates that the identification of vowel and consonant is dominated by the
      perception of acoustic cues characteristic of the set of stimuli used as well as
      by the strengths and weaknesses of the speech processing of the cochlear implant
      system. We did not find any systematic pattern in the results that could be
      related to the native language of the patients. These results suggest that vowel
      as well as consonant identification tests are effective means to compare the
      performance of cochlear implant patients even across different native languages.
      They also indicate that, in the future, one can conduct a fewer number of the
      many different (e.g. nonsense-syllable, word, sentence, speech-tracking) tests
      when evaluating the speech recognition abilities of patients with the implant.

PMID- 8265120
TI  - Synthesis of human cartilage using organotypic cell culture.
AB  - The limited supply of fresh autologous cartilage tissue for use in reconstructive
      surgery necessitates the use of vital banked allografts. A feasible in vitro
      production of cartilage tissue composed of living cells requires the use of
      modern tissue culture techniques retaining the phenotypic characteristics of
      chondrocytes. With this purpose in mind, human chondrocytes were isolated and
      cultured using different culture procedures: monolayer, suspension and agar gel.
      The differentiation state of chondrocytes as well as proteoglycan and collagen
      syntheses were assessed by histochemical and immunohistochemical methods. Whereas
      chondrocytes in monolayer displayed an unstable phenotype and tended to
      dedifferentiate, in three-dimensional culture the chondrocytes remained
      morphologically, phenotypically and functionally differentiated. Furthermore, an
      accumulation of matrix products pericellularly was observed in the agar gel. The
      results suggest that three-dimensional cultures in agar gel may allow the in
      vitro production of bioartificial cartilage for transplantation.

PMID- 8265121
TI  - Nasal mucociliary clearance in patients with upper and lower respiratory
      diseases.
AB  - The nasal mucociliary clearance was measured in 71 subjects with nasal allergy
      (NA) (56 subjects without sinusitis and 15 with sinusitis), 12 subjects with
      bronchial asthma (BA) (7 without, 5 with) and 7 subjects with aspirin-induced
      asthma (AIA) using a saccharin test. The results were compared with those
      obtained in a control group of 15 healthy subjects. The saccharin time (ST)
      values for both NA and BA subjects without sinusitis (16.9 +/- 9.9 and 20.1 +/-
      9.4 min, respectively) did not differ from that of the healthy subjects (16.3 +/-
      5.3 min). However, ST values in NA and BA subjects with sinusitis (37.6 +/- 22.9
      and 57.0 +/- 6.7 min, respectively) were significantly higher than those of
      healthy subjects (p < 0.01). The ST value of AIA subjects (13.0 +/- 5.4 min)
      showed no significant difference compared with that of the control group. These
      results suggest that allergic reactions do not influence the nasal mucociliary
      clearance and that the property of mucus complicated with sinusitis is important.
      Also, sinusitis observed in AIA may be somewhat different from ordinary sinusitis
      complicated with NA and BA.

PMID- 8265122
TI  - [Diabetic coma and bases of proper treatment].
AB  - Hyperglycaemic, hyperosmolar coma developing in diabetes mellitus-with or without
      ketoacidosis-is a perilous metabolic catastrophe, preserving its clinical
      importance even nowadays. The features of the two basic forms of diabetic coma,
      the development and characteristics of clinical symptoms and laboratory
      alterations caused by absolute or relative lack of insulin are reported by the
      author. The importance of early diagnosis and up-to-date intensive treatment is
      emphasized, regarding the need of decreasing of the still now considerable
      mortality rate. Fundamental principles of the therapeutic interventions are the
      following: improvement of the microcirculation through appropriate compensation
      of fluid and elektrolytes, intravenous or intramuscular administration of low
      dose insulin, prevention of hypokalemic condition, and correction of acidosis
      under pH 7,1 value. Moreover, the well-planned supportive treatment is also
      essential: prevention of thromboembolism, averting the occasional development of
      shock caused usually by infections, and prophylaxis of the often fatal cerebral
      oedema. The estimation and follow-up of osmolality and the prevention of rapid
      changes in serum glucose and electrolyte levels are of particular importance in
      every cases. Careful observation of the patients regarding the cardiorespiratory
      and renal functions is of great significance in both (first and second) phases of
      the treatment. Improvement of patients' education, controlled care of diabetic
      patients, reduction of the number of recidive cases and increasing knowledge
      regarding diabetes among the general practitioners are determined by the author
      as the future possibilities for the prevention of this severe metabolic disorder.

PMID- 8265123
TI  - [Management of complications from endoscopic sphincterotomy].
AB  - Endoscopic sphincterotomy can replace operation. It was to be chosen in case of
      recurrence common bile duct calculi. The authors describe 11 complicated cases
      (2.01%) (9 women, 2 men) which demanded surgical management out of the 546
      endoscopic sphincterotomy performed during 10 years (1982-1991). Operations were
      performed on 6 patients and 3 of them died (0.55%). Operation was necessary
      because of perforation and bleeding (2 perforations, 2 bleedings, 2 bleedings and
      perforations at the same time).

PMID- 8265124
TI  - [Immunotherapy of superficial bladder tumors in a hospital department].
AB  - Since 1988 27 patients with bladder cancer - in the T1, G1, G2 stage - have been
      treated by intra-cavitally applied BCG (Pasteur). The follow-up period was 12-62
      months. There was no relapse in 18 cases (66%) in 4 cases (16%) increase the
      average relapse rate, in 5 cases the treatment was unsuccessful. These results
      suggest that the treatment is effective, affordable and occur few complications.

PMID- 8265125
TI  - [Intracranial arteriovenous malformation associated with multiple cutaneous
      follicular hamartoma. A new syndrome].
AB  - A case of 32-year-old man with neurocutaneous syndrome has been reported. The
      clinical picture is characterized by dominance of lesions of central nervous
      system beginning at early lifeperiod of patients with intermittent slow
      progression and with a variety of different symptoms, and with presence of
      multifocal intracranial space-occupying process resulting death. The
      pathomorphological alterations consist of multiple congenital developmental
      anomalies including vascular hamartosis of central nervous system and hair
      follicular hamartosis of skin. It is suggested that the distinct syndrome seems
      to be a new one regarding both association of intracranial arteriovenous
      malformation with multiple cutaneous follicular hamartoma and the speciality of
      cutaneous damage itself, which differs from other hair follicular hamartomas
      hitherto described. The alteration of skin may represent a follicular hamartoma
      of generalized type with differentiation in Headington's classification. The
      literature is briefly reviewed.

PMID- 8265126
TI  - [Morphological properties of preblastomatous conditions in organs and tissues I].

PMID- 8265127
TI  - [Iconography of Semmelweis].

PMID- 8265128
TI  - [Jean Martin Charcot (1825-1893)].

PMID- 8265129
TI  - [Indications for organ-conserving operations in cases of kidney tumors in the age
      of radical surgery].
AB  - The authors analyze the experiences of 29 operations of malign renal tumors,
      performed during the last 10 years conservating the organs. In 20 cases the
      conservation of the organ was indicated by necessity due to some diseases or the
      lack of the contralateral kidney, and in 9 cases due to the small extension of
      the tumor. The authors reveal their experiences on preoperative examinations;
      they discuss some questions of surgical techniques and describe their system of
      patient control. Based upon their experiences, in selected cases they consider
      indicated conservation of the organ, if the tumor can be extirpated ablastically.

PMID- 8265130
TI  - [Arrhythmogenic right ventricular dysplasia. Case report and review of the
      literature].
AB  - Two cases of arrhythmogenic right ventricular dysplasia are described. The most
      important clinical features of the disease are malignant ventricular arrhythmia
      and sudden death. It is characterized by the loss of right ventricular
      musculature and by the fatty and connective tissue infiltration of the right
      ventricular wall. The diagnosis is based on the typical echocardiographic
      appearance of right ventricular dilatation, on the presence of negative T waves
      in leads V1-4 on the resting ECG and on ventricular tachycardia of left bundle
      branch block pattern. Right heart failure develops only in the late phase of the
      disease. Genetic defect might be an etiologic factor. In conclusion authors
      suggest that in case of left bundle branch block ventricular tachycardia or Adams
      Stokes syndrome in young adults echocardiography and family screening are
      necessary.

PMID- 8265131
TI  - [Transcervical endometrial resection. A new surgical method for the management of
      metrorrhagia].
AB  - The authors introduce to transcervical endometrial resection offered as an
      alternative operation for women with metrorrhagia. Their experience regarding to
      the introduction and results of the surgery of the first 10 patients are
      reported. There were no intraoperative complications. The benefit of the new
      technique regarding to the shorter hospital stay and recovery time is obvious.

PMID- 8265132
TI  - [Bilateral torticollis].
AB  - Bilateral torticollis is a very rare form of a well known deformity i.e. muscular
      torticollis. This malformation might present a differential diagnostic problem
      both for orthopaedic surgeons and ophthalmologists, as well as, for neurologists.
      In agreement with the literature, the role of an injury during labour or
      defective embriogenesis is suggested to play a part.

PMID- 8265133
TI  - [Congenital absence of the pericardium].

PMID- 8265134
TI  - [Early detection of cancer of the colon and small intestine. Diagnosis based on
      occult intestinal hemorrhage].

PMID- 8265135
TI  - [Competencies for nursing by engagement and achievement. Interview by Harald
      Verworner].

PMID- 8265136
TI  - [Educational reform: the college model in the teaching experiment].

PMID- 8265138
TI  - [Project related teaching].

PMID- 8265137
TI  - [Marching towards a new tomorrow--Margretta Madden Styles].

PMID- 8265139
TI  - ["I miss meeting you as a speaker"].

PMID- 8265140
TI  - ["Nervousness reached its peak". Interview by Harald Verworner].

PMID- 8265141
TI  - [7. Meeting of the Czech Nursing Association. A report by Dr. Rosemarie Walter
      which allows a comparison between the opportunities for nursing education in the
      Czech republic and in Austria].

PMID- 8265142
TI  - [Educational reform: a distinct viewpoint of the Austrian Nursing Association].

PMID- 8265143
TI  - [Nursing education in the operating room].

PMID- 8265144
TI  - Measurement of glare sensitivity in cataract patients using low-contrast letter
      charts.
AB  - The Committee on Ophthalmic Procedures Assessment of the American Academy of
      Ophthalmology suggested using low-contrast visual acuity measured before and
      after adding a glare source as a test for assessing overall visual disability
      from immature cataracts. We have developed a test that follows the Committee's
      three principles of design, and we report that the effect of glare on visual
      acuity is considerably greater for recognizing low-contrast letters than for
      recognizing high-contrast letters. The effect of glare on visual acuity increases
      progressively as letter contrast is reduced in the stages 96%, 50%, 25%, 11% and
      4%. The 25% chart (and possibly the 11% chart) gives the most suitable
      sensitivity for eyes with immature cataracts. Age-related brunescence and aging
      itself do not necessarily produce high sensitivity to glare. Sensitivity to glare
      was markedly different in eyes with different kinds of cataract.

PMID- 8265145
TI  - Effect of light filters on contrast sensitivity function in normal and retinal
      degeneration subjects.
AB  - Contrast sensitivity functions were measured with five light filters and without
      a filter, in the presence of a glare source, in 12 retinal degeneration subjects
      and 9 normal subjects. The light filters included yellow-tinted, CPF 527, NoIR
      111, 0.6 neutral density and sunglasses with a 95% UV filter. Retinal
      degeneration subjects showed a mild improvement in contrast sensitivity at the
      higher spatial frequencies and maintained mean log contrast sensitivity with
      light filters which reduced photopic light transmission up to 75%. Normal
      subjects exhibited a systematic decrease of contrast sensitivity at higher
      spatial frequencies with all light filters and overall mean log contrast
      sensitivity was significantly correlated (r = 0.86, P < 0.025) with photopic
      light transmission of the filters. It is concluded that, when in the presence of
      a glare source, the benefits of certain light filters to retinal degeneration
      subjects is related to the reduction of overall photopic luminance.

PMID- 8265146
TI  - Clinical evaluation of a range of autorefractors.
AB  - A practice-based study of nine autorefractors was undertaken to assess
      reliability and validity. Various statistical methods were used to test aspects
      of validity of the machines compared with one another. In routine optometric
      practice the autorefractor is shown to be a useful complement to existing
      techniques, but there is a measurable difference in the performance of machines
      from different manufacturers, and even between two models from the same
      manufacturer.

PMID- 8265147
TI  - Decrease in stereoacuity in the seventh decade of life.
AB  - We measured stereoacuity in 41 subjects with normal Snellen acuity in each eye,
      and normal ocular health. Patients were measured in each of the age ranges 21-28,
      41-49, 51-59 and 60-70 years. Stereoacuity was reduced from about 16 sec arc for
      the three younger groups to about 27 sec arc for the older subjects. Since
      stereopsis has a cortical neural substrate, these data suggest that there may be
      cortical changes affecting the interaction of information from the two eyes with
      advancing age, but whether these changes result from loss of contrast
      sensitivity, instability of ocular alignment or binocular stress, all of which
      have been reported in elderly subjects, is not known.

PMID- 8265148
TI  - Reliability of visual performance measurement under optical degradation.
AB  - Small groups of experienced subjects wore three types of bifocal contact lens
      which were shown to reduce visual performance at distance and near conditions.
      Monitor-based contrast sensitivity, Pelli-Robson contrast threshold, and high-
      and low-contrast visual acuity were each measured on two separate occasions. For
      each bifocal contact lens type the test-retest difference did not increase
      significantly with reduction in visual performance. Despite this the reliability
      of the visual performance measures was shown to be reduced compared to previous
      reports with normal well-corrected subjects and the test-retest repeatability
      coefficients (95% confidence limits) increased as the average visual performance
      declined. The poor reliability is of interest to the practitioner fitting bifocal
      contact lenses, and confirms previous suggestions that reliability may be related
      to visual degradation (e.g. ocular disease). In addition Pelli-Robson contrast
      thresholds were shown to be correlated with the spatial frequency represented by
      the presumed fundamental frequency of the component letters.

PMID- 8265149
TI  - Temporal characteristics of proximally-induced accommodation.
AB  - This study sought to determine whether proximally-induced accommodation (PIA) is
      capable of sustaining an accommodative response over time. Accordingly, the
      steady-state PIA response was measured during the course of a continuous 5 min
      stimulus period for targets located at distances of 0.2 or 6 m. The vergence and
      accommodation loops were opened by subjects (n = 8) monocularly viewing the
      targets through a 0.5 mm pinhole, while accommodation was assessed using an
      objective, open-field, infrared optometer. The mean PIA response did not change
      significantly during the fixation period. This finding suggests that PIA is
      indeed capable of maintaining a sustained response. This observation is
      consistent with the constancy of apparent target distance perception during
      extended fixation of a stationary object of regard under these conditions.

PMID- 8265150
TI  - Modelling sensitivity losses in ocular disorders: colour vision anomalies
      following intense blue-light exposure in monkeys.
AB  - The effects of prolonged exposure to intense, short-wavelength light were studied
      in monkeys through the measurement of increment-threshold spectral sensitivity
      (ITSS) and threshold-versus-intensity (TVI) functions using a behavioural method.
      The long-term effect of intense blue-light exposure was to induce a short
      wavelength (SW) sensitivity loss which did not depend on the intensity or
      chromatic composition of the adapting field. The TVI curves for short wavelength
      stimuli revealed an increase in test threshold without changes in field
      sensitivity. Since this SW sensitivity loss may generalize to characteristic
      colour vision defects found in many outer retinal diseases, models of acquired
      alterations of colour vision mechanisms are considered. These models describe
      probable changes in ITSS functions and TVI curves in diseases affecting the inner
      or outer retina as well as changes in dark adaptation.

PMID- 8265151
TI  - Weight of edged spherical lenses in simulated eyewire shapes.
AB  - Eyewire shapes of some currently available spectacle frames were constructed
      mathematically and weights of spherical lenses cut to these shapes were computed
      for different decentrations in three commonly used lens materials. The results
      confirm a previous observation that the edged shape of a negative lens has only a
      minor effect on its weight, although this is often not the case for positive
      lenses. The appropriate diameters of circular centred lenses to be used in
      comparing lens weight for different materials were also examined. Relative to
      those adopted in previous studies, it was found that the weight of a larger lens,
      58 mm diameter for negative lenses and 65 mm diameter for positive lenses, would
      more adequately represent the average weight of edged lenses in modern spectacle
      frames.

PMID- 8265153
TI  - Notch in contrast sensitivity function of optical origin: diffraction effects of
      acrylic filters.
AB  - A series of retinal image degrading filters was evaluated by measuring the
      contrast sensitivity function of four human subjects through the filters
      (residual CSF). The acrylic filters, with regularly spaced cross-hatches,
      produced progressively more reduction in the residual CSF as the density of the
      cross hatching increased. For some of the filters there was a selective loss of a
      narrow band of spatial frequencies as a result of diffraction effects. This
      experiment serves to further emphasize the need to rule out optical causes of
      such notches in the CSF before making a diagnosis of neurological dysfunction.

PMID- 8265152
TI  - Open trial of subjective precision tinting: a follow-up of 55 patients.
AB  - We gave glasses, tinted using new techniques, to 55 patients with visual
      discomfort and a range of associated complaints. The techniques permitted the
      patients to adjust the colour and saturation of tint for maximum clarity and
      comfort when viewing text. Benefit was experienced by 45 patients (82%) who were
      still using them more than 10 months later. Of these, 40 presented with a
      perceptual distortion of text that the glasses alleviated; 86% reported migraine
      in the family. An independent series of 74 children with reading difficulty was
      examined using coloured plastic sheets placed upon a page of text. Of those
      reporting beneficial effects of colour, 60% had migraine in the family, as
      compared with 31% of those for whom colour was of no benefit.

PMID- 8265154
TI  - Red-green flicker resolution as a function of heterochromatic luminous
      modulation.
AB  - Critical fusion frequencies have been evaluated in heterochromatic red-green
      flicker as a function of red-green luminous modulation defined by mL = (R
      G)/(R+G)%, at five different mean luminance levels, two test sizes (2 degrees and
      5 degrees) and square wave stimuli. The extreme values mL = +/- 100 correspond to
      ordinary light-dark flicker (red or green); mL = 0 corresponds to pure chromatic
      flicker, and any other values correspond to simultaneous luminous and chromatic
      flicker. To implement the stimuli we have developed a new stimuli generator
      (AVICO, colour vision analyser) using bicolour LEDs as the light source and
      electronic control of the luminances and frequencies. The results for any
      luminance level and both test sizes show a minimum critical fusion frequency in
      the case of pure chromatic flicker (photometric match condition) and a critical
      fusion frequency which is slightly higher in the green extreme (mL = -100) than
      in the red (mL = +100). The shape of the variation between the minimum and the
      extremes is consistent with the results recently reported by Swanson and the
      theoretical models for the luminance channel response to heterochromatic flicker.

PMID- 8265155
TI  - Diffractive properties of the Diffrax bifocal contact lens.
AB  - We have verified that the Pilkington Diffrax lens behaves optically as a
      diffractive bifocal contact lens. The longitudinal chromatic aberration of the
      lens is similar to that predicted by theory, both on and off the eye. The over
      refraction with the lens on the eye is similar to the distance subjective
      refraction, which is also as predicted.

PMID- 8265156
TI  - Calibration of the Canon Autoref R-1 for continuous measurement of accommodation.
AB  - The Canon Autoref R-1 is an infrared optometer which allows free-space viewing.
      Pugh and Winn described hardware modifications necessary to convert the Autoref R
      1 from an instrument capable of taking single static measurements of the eye's
      accommodative (refractive) status to an instrument capable of continuous
      measurement of the accommodative status of the eye. We describe two methods of
      calibrating the Autoref R-1 for continuous measurement of accommodation for any
      individual eye. The assumptions and sources of error underlying these calibration
      techniques are discussed. We also describe further hardware modifications to
      simplify signal acquisition from the Autoref R-1.

PMID- 8265157
TI  - Clinical norms for amplitude of accommodation in Chinese.
AB  - Amplitude of accommodation was measured in 121 Hong Kong Chinese subjects between
      the ages of 11 and 65 years, using the 'push-up' method and the results compared
      with those previously obtained for Caucasian subjects. The results confirm and
      quantify clinical experience that Chinese people have lower amplitudes of
      accommodation than Caucasians. If presbyopia is considered to commence when the
      amplitude of accommodation declines to less than 5 D, then presbyopia in the
      Chinese race occurs between the ages of 36 and 40 years. By early in the second
      decade of life the amplitude of accommodation in the Chinese is already lower
      than that of Caucasians. This suggests that reduced amplitude of accommodation
      may be due, at least in part, to factors other than longterm environmental
      effects.

PMID- 8265158
TI  - Location of conjugate points in an optical system with particular reference to
      the estimation of aniseikonia in the pseudophakic eye.

PMID- 8265159
TI  - Explanation for the observation of isogyres in crystalline lenses viewed between
      crossed polarizers.

PMID- 8265160
TI  - Determination of the cardinal positions of a lens system by the 'step-along'
      method.

PMID- 8265161
TI  - Intraocular pressure measurement in children.

PMID- 8265162
TI  - Relative effectiveness of different modes of glaucoma screening in optometric
      practice.
AB  - This study analyses records from 189 optometric practices in England and Wales on
      the glaucoma screening of 123,415 patients aged > 40 years during a prospective 6
      month period. Its purpose is to compare the effectiveness of the various modes of
      screening which were used. All optometrists tested every patient by
      ophthalmoscopy. The 146 who, in addition, conducted tonometry on a routine basis
      detected a confirmed glaucoma in 0.35% of their patients, whilst the 43 who used
      tonometry 'on suspicion' detected a case in 0.25%, (P < 0.02). The 47
      optometrists who conducted perimetry frequently (i.e. in > or = 15% of sight
      tests) detected a case in 0.46% of patients, whilst the other 142, who did little
      or no perimetry, detected a case in 0.29%, (P < 0.001). Eleven optometrists who
      relied mainly on ophthalmoscopy had a detection rate of only 0.12%. Optometrists
      with the most comprehensive modes of screening had the greatest referral
      accuracy. It was concluded that more widespread adoption of routine tonometry for
      people aged approximately greater than 40 years is necessary to reduce the
      present substantial number of false negatives; and that the frequent use of
      visual field analysis is additionally required to achieve the best results.

PMID- 8265163
TI  - Mechanical manipulation of the lids and tear break-up time measurements in Hong
      Kong Chinese.
AB  - We measured tear break-up time (TBUT) after lid-rubbing in a single masked
      experiment, and found that TBUT was unaltered. A further single masked experiment
      in which non-invasive tear break-up time (NITBUT) was measured after the lids
      were raised as if to apply fluorescein also showed no effect of this interference
      with the lids. An experiment in which fluorescein was applied either with the lid
      raised or not raised during fluorescein application, again with the experimenter
      masked with respect to treatment, also produced no significant difference in
      TBUT. When we measured TBUT with the lid raised so that it was not in contact
      with the cornea, there was no difference in TBUT for the group between the
      'lifted' and 'non-lifted' eye; some subjects showed substantially shorter TBUT
      values, while others showed substantially longer TBUT values. These findings are
      surprising in view of the concerns expressed in the literature regarding the
      sensitivity of the tear film to mechanical interference, and suggest that the
      tear film is more resistant to disruption than has previously been thought.

PMID- 8265164
TI  - Influence of proximal, accommodative and disparity stimuli upon the vergence
      system.
AB  - The most important cues to the normal vergence response are retinal disparity,
      accommodative effort and perceived distance (proximal cue). In the past, proximal
      cues have been thought to contribute little to the total vergence response but
      more recent studies have suggested that they play an important role. The relative
      contributions of the proximal, accommodative and disparity cues to the vergence
      response were assessed by measuring the effect upon the vergence system when each
      of these cues were altered. The effect upon the vergence system was measured by
      the change in 'phoria, the change of fixation disparity and the amount of prism
      adaptation after 210 s of binocular viewing. The results indicate that the
      greatest effect of cue disharmony occurred when the proximal and disparity cues
      were altered. A finding which signifies the importance of the proximal cue to the
      overall vergence response.

PMID- 8265165
TI  - Accommodation and chromatic aberration: effect of spatial frequency.
AB  - When subjects view an edge in white light, a colour fringe, produced by
      longitudinal chromatic aberration (LCA) of the eye, is formed at the edge. The
      colour fringe changes with changes in focus, and serves as a complex colour-coded
      cue for reflex accommodation. Fincham found that 60% of his subjects failed to
      accommodate appropriately when the colour fringe was removed with an
      achromatizing lens or by the use of monochromatic light. Our experiment sought to
      determine the spatial frequencies at which LCA is most effective. We monitored
      accommodation in 10 subjects while they viewed sinusoidally moving sine-wave
      gratings (1-3 D at 0.2 Hz; 1-10.5 c/deg) in a Badal optometer. The targets were
      'white' gratings with LCA normal, doubled, neutralized or reversed. Doubling the
      aberration has minimal effect, removing the aberration reduces gain and increases
      phase-lag, and reversing the aberration severely disrupts accommodation.
      Sensitivity to these chromatic cues exists at all spatial frequencies tested, but
      is most prominent between 3 and 5 c/deg. These results support the view that the
      system monitors focus by comparing contrast in red-green and perhaps blue-yellow
      colour-opponent mechanisms.

PMID- 8265166
TI  - Accommodative and pupillary responses to sinusoidal target depth movement.
AB  - We evaluated the accommodative and pupillary responses to sinusoidal target depth
      movement in 10 normal subjects and one patient by analysing frequency responses
      and associated Bode plots. The phase of the pupillary response significantly
      lagged behind that of accommodative response, which suggests that they are
      controlled by separate central nervous systems. We measured the baseline shift of
      each response trace using a regression line and found that they were larger at
      higher stimulation frequencies. A patient with severe asthenopia showed a
      considerable baseline shift in accommodative response. These analyses may be
      useful for the quantitative assessment of dynamic accommodation and pupillary
      response.

PMID- 8265167
TI  - Effect of target luminance on microfluctuations of accommodation.
AB  - It is feasible that small temporal variations in steady-state accommodation may
      provide feedback to the accommodation control system through changes in retinal
      image contrast and that this feedback may be used to maintain an optimal
      accommodation response. The complex waveform of microfluctuations is dominated by
      two distinct regions of activity; a low frequency component (LFC < 0.6 Hz) and a
      high frequency component (1.0 < or = HFC < or = 2.3 Hz). Whereas the HFCs appear
      to be correlated with some intraocular manifestation of arterial pulse the
      contribution of the LFCs to the control of steady-state accommodation is unclear.
      The present study investigates the effect of target luminance on the waveform of
      accommodative microfluctuations. Three young emmetropic observers viewed
      monocularly a high contrast (90%) Maltese cross target placed at a vergence equal
      to their dark-focus level of accommodation in a Badal stimulus system. The
      luminance of the target was varied from 0.002 to 11.63 cd m-2 in nine equal
      logarithmic steps. Five continuous accommodation signals were collected for each
      viewing condition at a sampling rate of 102.4 Hz, and average power spectra
      subsequently calculated with a frequency resolution of 0.1 Hz. One-way ANOVA
      revealed a significant variation in the root-mean-square (r.m.s.) value of the
      microfluctuations (F = 19.795, d.f. 124, P = 0.0001) which could be attributed
      mainly to increases in the r.m.s. value for the two lowest luminances (0.002 and
      0.004 cd m-2). Power spectrum analysis revealed that these changes in the
      microfluctuations could be attributed to increases of power in the LFC.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8265168
TI  - Tonic accommodation: a review. I. Basic aspects.
AB  - In the absence of an adequate visual stimulus, accommodation adopts an
      intermediate position of approximately 1 D. Since this position was believed to
      reflect the level of tonic innervation to the ciliary muscle, this response has
      been termed tonic accommodation (TA). Part I of this review will consider various
      aspects of this parameter, including its reference to closed-loop accommodative
      function and autonomic physiology. In addition, both the methods of measurement
      and appropriate terminology for this function will be discussed. It is concluded
      that the response, which becomes apparent under so-called 'stimulus-free'
      conditions, in fact probably represents an aggregate response resulting from
      multiple, non-optical stimuli. Thus the designation tonic accommodation may not
      be appropriate, since it fails to describe accurately the heterogeneous
      composition of the stimulus-free accommodative response. An associated paper (to
      be published as part II of this review) will examine accommodative adaptation and
      both clinical aspects of TA and adaptation of TA.

PMID- 8265169
TI  - Effects of a visual task with cognitive demand on dynamic and steady-state
      accommodation.
AB  - Dynamic accommodative response before and after, and steady-state accommodation
      during, a visual task were measured using an infrared optometer to investigate
      the effects of psychological stress on accommodative facility. Increase in the
      post-task dynamic accommodation response time (for a near-to-far condition) was
      greater for a group of subjects given a mental task at a higher presentation
      speed. In addition the steady-state accommodation showed an inward shift under a
      closed-loop condition which was enhanced when computation time was decreased.
      However, an inward shift was not evident when the performance level of subjects
      increased following training. The relationship between psychological stress,
      cognitive demand and accommodative function is discussed.

PMID- 8265170
TI  - Estimation of the thickness of the crystalline lens from on-axis and off-axis
      Scheimpflug photographs.
AB  - Measurement of human lens biometry directly from Scheimpflug images of the
      anterior ocular segment may be impossible when pupil size precludes an adequate
      Scheimpflug view of the posterior lens surface. The authors describe a simple and
      accurate geometric method of overcoming this problem by estimating the true lens
      thickness from pairs of on-axis and off-axis Scheimpflug images. The method is
      validated and the variability of the estimate is quantified. This new method has
      utility in the study of lens biometry in subjects with large lenses whose pupils
      cannot be adequately dilated.

PMID- 8265171
TI  - Effect of induced fixation disparity by negative lenses on the visually evoked
      potential wave.
AB  - The effect of induced fixation disparity produced by negative lenses and base-in
      prisms on the pattern visually evoked potential (VEP) was investigated. Monocular
      and binocular pattern reversal VEP were recorded through the negative lenses and
      base-in prisms using a 9.5 min arc check size. The results suggest that the mean
      binocular amplitude was 27% larger than the mean monocular amplitude which
      indicates partial summation in the absence of negative lenses or base-in prisms.
      A reduction of the binocular VEP amplitude appears to arise in the presence of
      fixation disparity induced by both the negative lenses and base-in prisms. Both
      the prisms and the negative lenses had no appreciable effect on the monocular VEP
      amplitude.

PMID- 8265172
TI  - Colour and flicker thresholds for high frequency increments.
AB  - Previous investigators have elicited spectral sensitivity functions for the
      chromatic and achromatic systems by manipulating the stimulus spatiotemporal
      parameters. An alternative strategy for obtaining these two functions is to use a
      single set of stimulus parameters and vary the threshold criterion. This can be
      accomplished by determining colour and flicker thresholds for a high frequency
      train of increments. In the current study, spectral sensitivity functions, based
      on colour and flicker thresholds, were determined for increments presented at 25
      Hz. The colour and flicker threshold functions are similar in form to those
      previously published for the chromatic and achromatic systems. The existence of
      distinct threshold functions for colour and flicker are interpreted in the
      context of parvo and magno pathways. Potential clinical applications of this
      model are discussed.

PMID- 8265173
TI  - Peripheral astigmatic asymmetry and angle alpha.
AB  - The association between peripheral astigmatic asymmetry and angle alpha was
      tested in the present study. Measurements were made in 34 eyes. Peripheral
      astigmatism was measured over the horizontal meridian using a Zeiss (Jena)
      Hartinger coincidence optometer and a Canon R-1 autorefractometer. Curves were
      fitted to the measured data of each eye and the minima determined by
      differentiation. Angle alpha was estimated by alignment of Purkinje images I
      (anterior cornea) and IV (posterior crystalline lens). Peripheral astigmatism was
      found to be symmetrical about a point on the nasal retina. This point departed
      from the visual axis by 8.8 +/- 7.0 degrees (Hartinger) and 9.4 +/- 9.8 degrees
      (Canon). Both values were found to be significantly higher than angle alpha 5.0
      +/- 1.2 degrees. The results indicate that either peripheral astigmatic asymmetry
      is due to additional factors such as lack of symmetry in the peripheral curvature
      of individual optical surfaces, or that there is further misalignment of optical
      surfaces away from an optical axis.

PMID- 8265174
TI  - Rabbit corneal endothelial cell membrane potential.
AB  - Membrane potential of rabbit corneal endothelial cells measured using
      microelectrodes was -29.3 +/- 0.8 mV, n = 45, (mean +/- SEM). Histological
      location of Lucifer Yellow dye iontophoresed out of the microelectrode confirmed
      that the microelectrode was located intracellularly. The Lucifer Yellow diffused
      five to six cell diameters away from the impaled cell indicating endothelial cell
      coupling. Depolarization by ouabain (10(-4) M) and high extracellular potassium
      (potassium for sodium substitution) showed the cells to be responsive to changes
      in the bathing solution whilst impaled, that the cell membrane is more permeable
      to potassium than sodium and that membrane bound Na(+)-K(+)-ATPase activity
      generates the transmembrane electrolyte gradients.

PMID- 8265175
TI  - Ocular rotation factor and orientational demand with astigmatic lenses.
AB  - Ocular movements required in most visual functions are affected by lenses in
      front of the eye. Fundamental to an understanding of these movements are concepts
      such as the ocular rotation factor and the ocular orientational demand. In this
      paper the ocular rotation factor for thin spherical lenses is generalized for
      astigmatic lenses. A compact matrix equation is obtained for the orientational
      demand in the case of such lenses. The equations are satisfactory in ordinary
      situations but they break down under certain circumstances. Equations are derived
      for these special circumstances in particular and also for all circumstances in
      general.

PMID- 8265176
TI  - Tonic vergence, age and clinical presbyopia.
AB  - The relative contribution of tonic vergence to the maximum near vergence response
      as a function of age and the development of presbyopia has received little
      attention. Tonic vergence position was measured subjectively in a group of 50
      subjects between 20 and 68 years of age. While there was no progressive trend
      with age, tonic vergence did exhibit a small but consistent convergent increase
      after 40 years of age. Thus, tonic vergence showed a slight change, possibly of a
      motor adaptive nature, concurrent with increasing age and the development of
      clinical presbyopia.

PMID- 8265177
TI  - Role of heredity in the genesis of myopia.
AB  - Previous studies suggest that myopia in parents may influence the genesis of
      myopia in their offspring. In this study, we surveyed 2888 children of Chinese
      descent in China and Hong Kong to determine the relationship between the
      refractive state of parents and their children. The age range of the children was
      7-17 years. Refraction was measured using a Canon R-22 objective infrared
      autorefractor and a survey on family history of ametropia was conducted using a
      questionnaire. We found that children with myopic parents are more likely to be
      myopic.

PMID- 8265178
TI  - Ophthalmic contact lens with internal fixation light for examination of the optic
      nerve head.
AB  - Stereoscopic slitlamp examination of the optic nerve head in one-eyed patients is
      difficult because there is currently no way to provide the patient with a
      fixation target. This situation is often aggravated in glaucoma patients by a
      miotic and fixed pupil. We have developed a funduscopic contact lens which
      incorporates a fixation target, allowing the patient to view the target with the
      eye being examined. The device has been successfully tested on normal volunteers.

PMID- 8265180
TI  - Calculation of the cardinal points of an optical system.

PMID- 8265179
TI  - Off-axis measurements of a plano distance power progressive addition lens.
AB  - To test that the Humphrey Lens Analyzer can be used validly to measure off-axis
      powers of progressive addition lenses of low distance power, we made measurements
      of a plano distance progressive power lens with both a conventional focimeter and
      the Humphrey Lens Analyzer. The use of the Humphrey Lens Analyzer in two modes,
      one in which the lens rotated about a point corresponding to the centre-of
      rotation of the eye (mode 1) and one in which the lens rotated about its back
      surface centre of curvature (mode 2), gave off-axis power measurements which were
      similar to those of conventional measurements. In addition, the Humphrey Lens
      Analyzer in mode 1 gave prism measurements which were similar to conventional
      measurements. The Humphrey Lens Analyzer in mode 2 gave prism measurements which
      were less than those of conventional measurements, but the prism contours were
      similar and the differences were < 1 delta within 20 mm of the lens centre.

PMID- 8265181
TI  - Preliminary characterization of mucin from effusions of cleft palate patients.
AB  - Middle ear effusions from children undergoing myringotomy were classified into
      three groups-cleft palate, thick (mucoid), and thin (serous). Mucin was purified
      from each of the three groups using CsCI equilibrium density gradient
      centrifugation. Analysis of the cleft palate mucin on Sepharose CL-2B showed it
      was excluded and therefore of large molecular weight. It could be broken down
      into smaller glycopeptide units by proteolysis and these glycopeptides had, based
      on elution position, a larger hydrodynamic size than those from the thick mucin.
      Intrinsic viscosity measurements demonstrated that the intact mucins could be
      ranked in order of molecular space occupancy; cleft palate > thick > thin. Amino
      acid analysis showed the cleft palate mucin to have an amino acid composition
      similar to other mucins, with serine, threonine, and proline constituting 41% by
      weight of the protein core. Thiol analysis gave evidence of a possible difference
      in polymerization between the three mucins, in that thin (the smallest mucin)
      contained the lowest number of thiols. This preliminary analysis of cleft palate
      mucin suggests a mucin with larger glycopeptide units forming an intact mucin of
      larger hydrodynamic size than either thick or thin middle ear mucins from
      anatomically normal children.

PMID- 8265182
TI  - Craniofacial cephalometric evaluation in habitual snorers with and without
      obstructive sleep apnea.
AB  - Cephalometry has been used to evaluate soft tissue and craniofacial dimensions in
      moderate-to-severe obstructive sleep apnea syndrome (OSA), but rarely in habitual
      snoring, the preclinical stage of OSA. This study deals with craniofacial bone
      measurements in a sample of 28 male habitual snorers with and without OSA, and 10
      healthy non-snorers. Habitual snorers showed a significant decrease in sagittal
      dimensions of the cranial base and mandibular bone; there was also a shorter
      maxilla in group B (apnea plus hypopnea index more than 10) with respect to group
      A (apnea plus hypopnea index less or equal to 10). Facial height and angle
      dimensions were not different between snorers and non-snorers. These findings
      indicate that some habitual snorers may have some anatomic disposition to upper
      airway obstruction during sleep.

PMID- 8265183
TI  - Precise vocal cord medialization using an adjustable laryngeal implant: a
      preliminary study.
AB  - Treatment of symptomatic unilateral vocal cord paralysis is most frequently
      surgical. Medialization of the vocal cord using Teflon injection has proved
      effective; however, studies have shown this technique to produce stiffness of the
      vocal fold with loss of the "mucosal wave" and concomitantly poor vocal function.
      As well, overcorrection may occur and is not reversible. Isshiki type 1
      medialization thyroplasty has been shown to produce a substantial improvement in
      vocal quality, as well as preserve the mucosal wave. A number of problems
      encountered during the performance of Isshiki type 1 thyroplasty has led us to
      modify the original technique. We have developed a new implant that allows for
      precise, easily adjustable control of vocal cord medialization. To evaluate the
      degree of vocal cord medialization afforded by this implant, larynges of fresh
      male and female cadavers were used as an experimental model. In both larynges,
      vocal cord medialization was shown to occur in a predictable fashion for the
      anterior, middle, and posterior segments, as well as in the functionally
      important inter-arytenoid region. We believe the use of this implant in
      medialization thyroplasty will allow precise, atraumatic medialization of the
      paralyzed vocal cord. This greater control over positioning and ease of
      adjustment should contribute to enhanced vocal quality.

PMID- 8265184
TI  - Management of hydrocephalus resulting from acoustic neuromas.
AB  - Patients with large acoustic neuromas may have secondary obstructive
      hydrocephalus and occasionally significant neurologic deficit develops. At the
      House Ear Clinic, we have managed patients with hydrocephalus by
      translabyrinthine tumor removal without preoperative ventriculoperitoneal
      shunting. Forty-three patients with documented hydrocephalus who underwent
      acoustic neuroma removal have been reviewed. Six patients had neurologic deficit
      resulting from raised intracranial pressure before surgery. In each of these six
      cases, the deficit resolved after tumor removed without requiring shunting. Two
      patients had had ventriculoperitoneal shunts inserted because of neurologic
      deficit before referral for tumor removal. Two other patients underwent
      postoperative shunting for neurologic deficit --one at 2 weeks and one at 2
      years. Cerebral or cerebellar herniation was not noted in any case. Cerebrospinal
      fluid leak occurred in five patients (11.6%) and culture-positive meningitis in
      two patients (4.6%). We conclude that decompression by translabyrinthine tumor
      removal is a safe method of management for patients with hydrocephalus resulting
      from large acoustic tumors.

PMID- 8265185
TI  - Hearing improvement after conservative approach for large posterior fossa
      meningioma.
AB  - Hearing preservation during the posterior fossa surgery depends on many factors,
      including tumor size and site of origin. In many cases, regardless of the
      presumed tumor origin, the severity of the pure-tone loss or decline in speech
      discrimination on preoperative testing prompts the surgeon to choose a surgical
      approach (translabyrinthine or transcochlear) that negates the chance for
      postoperative functional hearing in the involved ear. We describe a 41-year-old
      woman with unilateral severe sensorineural hearing loss who experienced a
      remarkable recovery of hearing after combined retrolabyrinthine and retrosigmoid
      removal of a 4 cm petrous ridge meningioma using intraoperative cochlear
      monitoring. Despite the tumor size, early intraoperative loss of wave I and
      proximity of the tumor to the porus, complete tumor removal was accomplished with
      preservation of the cochleovestibular bundle. Three weeks postoperatively, the
      patient noted marked subjective improvement and speech audiometry demonstrated an
      improvement in word recognition, from 0% to 86%. This improvement has remained 1
      year postoperatively, with no evidence of persistent tumor on repeat MRI scan.
      The case report illustrates the possibility of not just hearing preservation but
      improvement after removal of even large posterior fossa meningiomas that do not
      directly invade the cochlear nerve itself.

PMID- 8265186
TI  - Retropharyngeal cellulitis: a manifestation of Kawasaki disease in children.
AB  - Kawasaki disease (KD) or mucocutaneous lymph node syndrome is an acute febrile
      illness with prominent vasculitic features. The cause is unknown and the disease
      is seen most commonly in young children. After its initial description in Japan,
      the disease was thought to be rare in the United States, but recognition has
      dramatically increased over the past decade. Common symptoms of the disease for
      which the otolaryngologist may be initially consulted include inflammation of the
      lips and oral cavity and acute cervical lymphadenopathy. We present a case of
      Kawasaki disease initially complicated by retropharyngeal soft tissue swelling.
      Similar reports are rare in the pediatric literature; however, no such reports
      appear in the otolaryngology literature.

PMID- 8265187
TI  - Natural ostiotomy vs. inferior antrostomy in the management of sinusitis: an
      animal model.
AB  - An animal model was used to compare the surgical treatment of chronic sinusitis
      by opening the natural ostium vs. inferior antrostomy. Fifteen rabbits had
      surgical occlusion of the natural maxillary sinus ostia to induce sinusitis. At a
      second operation, the sinuses were entered and in each animal the natural ostia
      was reopened on one side and an inferior antrostomy was performed on the opposite
      sinus. Eight weeks after these operations the sinuses were evaluated. No
      differences were found in antrostomy patency rates, gross evidence of acute or
      chronic inflammation, or light or electron microscopic findings between sinuses
      with natural ostiotomy and those with lower antrostomy. The gross appearances and
      light and electron microscopic findings are discussed.

PMID- 8265188
TI  - Function of the posterior cricoarytenoid muscle in phonation: in vivo laryngeal
      model.
AB  - The function of the posterior cricoarytenoid (PCA) muscle in phonation has not
      been well documented. To date, several electromyographic studies have suggested
      that the PCA muscle is not simply an abductor of the vocal folds, but also
      functions in phonation. This study used an in vivo canine laryngeal model to
      study the function of the PCA muscle. Subglottic pressure and
      electroglottographic, photoglottographic, and acoustic waveforms were gathered
      from five adult mongrel dogs under varying conditions of nerve stimulation.
      Subglottic pressure, fundamental frequency, sound intensity, and vocal efficiency
      decreased with increasing stimulation of the posterior branch of the recurrent
      laryngeal nerve. These results suggest that the PCA muscle not only acts to brace
      the larynx against the anterior pull of the adductor and cricothyroid muscles,
      but also functions inhibitorily in phonation by controlling the phonatory glottal
      width.

PMID- 8265189
TI  - The protective effects of allopurinol and superoxide dismutase on noise-induced
      cochlear damage.
AB  - Several studies have demonstrated that noise exposure may result in local
      vasoconstriction of cochlear vessels. The subsequent decrease in cochlear blood
      flow may lead to hypoxia and predispose to the formation of free oxygen radicals
      (FORs). If hypoxia occurs in response to noise exposure, then drugs that scavenge
      or block the formation of FORs should protect the cochlea from damage resulting
      from hypoxic or ischemic events as well as noise trauma. Rats were exposed to 60
      hours of continuous broad-band noise (90 dB SPL) and treated with superoxide
      dismutase-polyethylene glycol (SOD-PEG), allopurinol, or a control vehicle.
      Exposure to noise resulted in significant threshold shifts at each frequency
      tested (3, 8, 12, and 18 kHz) as measured by tone burst-evoked compound action
      potentials and cochlear microphonics recorded from the round window. Both of
      these thresholds in drug-treated animals were attenuated compared with animals
      exposed to noise alone. These findings show that SOD-PEG and allopurinol may
      preserve cochlear sensitivity associated with noise exposure. This suggests that
      noise-induced damage to the cochlea may be related to the activity of FORs.

PMID- 8265190
TI  - Giant pseudoaneurysm of the extracranial vertical artery.

PMID- 8265191
TI  - Otolaryngology and pregnancy--difficult management decisions.

PMID- 8265192
TI  - Sclerosing osteomyelitis of the mandible.

PMID- 8265193
TI  - Bilateral congenital dacrocystoceles.

PMID- 8265194
TI  - Facial nerve injury in cochlear implantation.
AB  - We present eight cases of FN dysfunction after cochlear implantation. Four
      mechanisms of injury are proposed. The most common injury occurs from the heat of
      a bur shaft rotating over the FN in the facial recess. Several suggestions are
      made to help prevent the type of injuries we have seen. Preoperative imaging and
      intraoperative FN monitoring may be of general assistance in avoiding injuries to
      the FN, especially in cases of revision surgery and congenital malformations.

PMID- 8265195
TI  - Poststapedectomy incus necrosis.

PMID- 8265196
TI  - Concepts of ethics in medicine.

PMID- 8265197
TI  - Closed-loop caloric, harmonic acceleration and active head rotation tests: norms
      and reliability.
AB  - Norms and test-retest data from 20 persons with normal hearing and balance
      function were obtained for bithermal caloric (BC) using a closed-loop irrigator,
      sinusoidal harmonic acceleration (SHA) and active head rotation (AHR) tests. Each
      subject was tested twice with each test, with at least 24 hours between retest.
      Results of BC testing indicate that a unilateral weakness of 30% should be
      present to confidently identify a significant inter-ear difference when using a
      closed-loop irrigator for stimulus. Test-retest correlations of unilateral
      weakness were extremely poor, reflecting the potential for considerable
      variability with this test. With the exception of asymmetry measures at 0.01 and
      0.02 Hz, SHA gain, phase, and asymmetry are very similar to previously published
      norms. Test-retest correlations were generally better than BC correlations, with
      phase measures having the highest test-retest correlations. AHR norms were
      obtained in three conditions, with eyes open and starting at a stationary target
      (AHR-EO), with eyes closed (AHR-EC), and with eyes open and fixated on a target
      moving synchronously with the head (AHR-FX). AHR-EO mean gain and phase were
      slightly less than that reported by other researchers, possibly as a result of
      differences in analysis algorithms, and had the poorest test-retest correlations.
      AHR-EC gain and phase were much more variable than AHR-EO between subjects, but
      showed very high test-retest correlations. AHR-FX gain, phase, and asymmetry are
      similar to those reported previously and have slightly better test-retest
      correlations than AHR-EO.

PMID- 8265198
TI  - Endoscopic surgical treatment of nasal and paranasal sinus inverted papilloma.
AB  - Most of the papers written in the past regarding surgical treatment of nasal and
      sinus inverted papilloma recommend aggressive surgical treatment-usually a
      medical maxillectomy with external or transantral ethmoidectomy. However, since
      the introduction of endoscopic diagnostic and surgical techniques for the
      treatment of nasal and sinus disease, the treatment of inverted papilloma
      requires review. In Europe, Waitz and Wigand1 and Draf* routinely treat inverted
      papilloma endoscopically, reserving extensive surgery for papilloma involving the
      maxillary sinus or for recurrent disease. Fifteen cases of inverted papilloma of
      the nose and paranasal sinuses are discussed in this article. Ten cases represent
      inverted papilloma treated primarily with endoscopic sinus surgery; five were
      endoscopically treated for secondary or recurrent disease. All primarily treated
      patients had disease limited to the nose, nasal cavity, ethmoid, sphenoid, or
      medial wall of the maxillary sinus. The one patient in whom a recurrence in the
      maxillary sinus developed laterally underwent a medial maxillectomy for control.
      All patients treated endoscopically have had their disease followed for a minimum
      of 1 year, with an average of 3 years. Four patients in this study had
      traditional surgery involving medial maxillectomy and ethmoidectomy for an
      initial diagnosis of inverted papilloma. These patients manifested recurrent
      papilloma into the sphenoid sinus bilaterally in one case, frontal sinus in
      another, and the maxillary sinuses in two other cases, and all patients have
      papilloma controlled endoscopically. Endoscopic nasal and sinus diagnosis and
      surgery is appropriate for diagnosis, followup, and treatment of both limited and
      recurrent inverted papilloma, provided all patients are made aware of the
      possibility of recurrent and need for more extensive surgery as a
      result.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265199
TI  - Management of carotid artery hemorrhage in middle ear surgery.
AB  - Iatrogenic injury to the carotid artery as it traverses the middle ear in its
      normal anatomic position is a rare but potentially life-threatening event.
      Predisposing factors include a thin or dehiscent plate of bone, which normally
      protects the artery at the level of the eustachian tube, erosive middle ear
      disease, or previous trauma. Prevention and management of carotid artery injuries
      in the middle ear are discussed with an applicable case report.

PMID- 8265200
TI  - K-antigens in Porphyromonas gingivalis are associated with virulence.
AB  - We investigated antigens in spreading and non-spreading Porphyromonas gingivalis
      strains. On the basis of differences in virulence in the mouse model, 8 strains
      were selected for antiserum production in rabbits. Hyperimmune sera were tested
      by double immunoprecipitation and immunoelectrophoresis. Besides a common
      antigen, differences in antigenic composition were observed in the thermolabile
      antigens between all strains tested. Two different heat-stable antigens were
      found after heating at 120 degrees C. One such antigen was detected after
      sonication of the pellet fraction of autoclaved P. gingivalis cells. This antigen
      cross-reacted with 6 of the 8 immune sera. This somatic antigen was almost
      neutrally charged and sensitive to sodium periodate treatment, suggestive of
      lipopolysaccharide. A second heat-stable antigen was detected in the supernatant
      of autoclaved strains of W83, W50, HG184 and A7A1-28. These non-somatic antigens
      were strain-specific, i.e., no cross-reactivity was found with heterologous
      hyperimmune sera. An exception was strain W50, which had a non-somatic heat
      stable antigen which was recognized by W83 antiserum. These antigens were
      resistant to DNAse, RNAse and proteinase-K treatment but were degraded by sodium
      periodate. In immunoelectrophoresis, these antigens appeared to be negatively
      charged. These properties are characteristics of a K-antigen, which likely
      represent a thermostable carbohydrate capsule. The presence of K-antigen
      correlates very well with the serum resistance, the low chemiluminescence, the
      resistance to phagocytosis and the need for opsonization with specific antibodies
      for complement-mediated killing of virulent P. gingivalis strains.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8265201
TI  - Modification of experimental Porphyromonas gingivalis murine infection by
      immunization with a polysaccharide-protein conjugate.
AB  - To better understand the role of the capsular polysaccharide in the virulence of
      Porphyromonas gingivalis, the effect of immunization with a polysaccharide
      protein conjugate on experimental murine infection was evaluated. The conjugate
      was prepared using polysaccharide isolated from P. gingivalis strain ATCC 53977
      and bovine serum albumin. One group of 22 mice was immunized by intraperitoneal
      injection with the conjugate and a control group of 25 mice was similarly
      immunized with bovine serum albumin. Serum antibody reactive to the
      polysaccharide, as determined by enzyme-linked immunosorbent assay, was elevated
      in the group of mice immunized with the polysaccharide-protein conjugate but not
      in the mice immunized with bovine serum albumin. Both groups of mice were
      challenged with P. gingivalis strain ATCC 53977 (10(10) cells) administered
      subcutaneously on the dorsal surface. Following challenge, the mice immunized
      with the polysaccharide-protein conjugate appeared healthier and demonstrated
      less weight loss than did the control group of mice. Ulcerative lesions at
      secondary locations were smaller in mice immunized with the polysaccharide
      protein conjugate. Thus, immunization of mice with a conjugate containing P.
      gingivalis polysaccharide could reduce the severity of but not prevent an
      invasive infection with P. gingivalis.

PMID- 8265202
TI  - Common and specific antigens of several treponemes detected by polyclonal
      antisera against major cellular proteins.
AB  - Thirteen polypeptide antigens with molecular weights ranging from 34 kDa to 83
      kDa were selected and their antigenic behaviors and distribution were examined in
      12 strains of microorganisms including Treponema, Borrelia, Leptospira and
      Leptonema. Immunoblot analysis demonstrated that 45 kDa and 83 kDa polypeptides
      of Treponema socranskii subsp. buccale ATCC 35534, 53 kDa antigen of Treponema
      denticola ATCC 33520 and 44 kDa polypeptide of the strain G7201 were strain
      specific. The 34, 62, 66 and 84 kDa polypeptide antigens were detected in all 8
      treponemal strains examined. T. denticola ATCC 33520 and ATCC 35404 possessed 38
      kDa, 48 kDa, 52 kDa and 72 kDa common polypeptide antigens. All 12 strains
      possessed the 84 kDa polypeptide antigen. Immunoelectron microscopy demonstrated
      that the 34 kDa and 38 kDa polypeptide antigens were located on the axial
      flagella and that other polypeptide antigens were located on the outer envelopes
      or wall-membrane complexes.

PMID- 8265203
TI  - Beta-hemolytic streptococci in advanced periodontitis.
AB  - The distribution of serotypes of beta-hemolytic streptococci was examined in 718
      periodontitis patients. Subgingival samples were obtained with paper points from
      the 3 deepest lesions in each patient, transported in VMGA III, plated onto
      brucella agar with 5% sheep blood and incubated anaerobically for 7 days.
      Serotyping and speciation were performed with Meritec-Strep Beta-Hemolytic
      Streptococcus Grouping Set and the Analytab 20S Streptococcus System. Beta
      hemolytic streptococci were recovered from 33.7% of patients and averaged 10.5%
      of the total viable counts in culture-positive subjects. The organisms occurred
      with higher prevalence in patients 35 years or older than in younger patients.
      The predominant serotypes were F (62.9%), non-typeable (18.1%), B (6.9%), C
      (6.9%) and G (5.2%). 100% of beta-hemolytic streptococci were sensitive to
      penicillin, but less than 5% were sensitive to tetracycline, metronidazole or
      ciprofloxacin. Beta-hemolytic streptococci may contribute to inflammatory
      periodontal disease and may interfere with healing after therapy.

PMID- 8265204
TI  - Salivary collagenase, elastase- and trypsin-like proteases as biochemical markers
      of periodontal tissue destruction in adult and localized juvenile periodontitis.
AB  - The profile of salivary proteases and their cellular origin, with special
      reference to polymorphonuclear leukocytes and bacteria, was studied in localized
      juvenile periodontitis and compared with adult periodontitis and healthy
      controls. General proteolytic activity in saliva as well as collagenase, elastase
      like and trypsin-like activity was measured. In addition, the sensitivity of
      salivary collagenase of patients with localized juvenile periodontitis to
      doxycycline inhibition was studied. The saliva of localized juvenile
      periodontitis patients contained low amounts of collagenase compared with adult
      periodontitis saliva, and almost all salivary collagenase was found to exist in
      endogenously active form, as was found to be the case also in adult periodontitis
      patients and healthy controls. The salivary collagenase of localized juvenile
      periodontitis patients was relatively insensitive to 100 mumol/l doxycycline but
      was completely inhibited by 600 mumol/l doxycycline, reflecting rather matrix
      metalloproteinase-1 (fibroblast-type) than matrix metalloproteinase-8
      (polymorphonuclear leukocyte) enzyme. The saliva of localized juvenile
      periodontitis patients also contained low amounts of elastase-like activity
      compared with the saliva of untreated adult periodontitis patients. Scaling and
      root planing caused a significant decrease in elastase-like activity in the
      saliva of adult periodontitis patients. General proteolytic and trypsin-like
      activities were also low in the saliva of localized juvenile periodontitis
      patients. Furthermore, the reducing agent beta-mercaptoethanol did not activate
      or inhibit the salivary trypsin-like activity of localized juvenile periodontitis
      or adult periodontitis patients, although the reductant readily activated
      partially purified Porphyromonas gingivalis trypsin-like protease in a
      characteristic manner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265205
TI  - Microbiology of the pericoronal pouch in mandibular third molar pericoronitis.
AB  - The microorganisms associated with mandibular third molar pericoronitis were
      investigated using direct microscopy and anaerobic culture method. The
      pericoronal pouch was sampled with paper points in A) 8 patients without
      mandibular third molar pericoronitis and B) 6 patients with mandibular third
      molar pericoronitis. Under the microscope, the microflora was found to be a
      complex mixture comprising gram-positive and gram-negative cocci, rods and
      filaments (including fusiform and curved rods), motile rods and spirochetes.
      Significantly higher proportions of motile, gram-negative rods were found in
      group B than in group A. The predominant cultivable microflora of 9 samples: A
      (4) and B (5) comprised several species of facultative and obligate anaerobic
      bacteria, namely Peptostreptococcus, Streptococcus, Actinomyces, Eubacterium,
      Propionibacterium, Veillonella, Porphyromonas, Prevotella, Bacteriodes,
      Fusobacterium, Campylobacter, Staphylococcus, Stomatococcus, Lactobacillus,
      Neisseria, Capnocytophaga, Haemophilus, Selenomonas and Centipeda species. The
      microflora in pericoronitis appeared similar to that of diseased periodontal
      pockets.

PMID- 8265206
TI  - Acquired resistance and persistence of Candida albicans following oral
      candidiasis in the mouse: a model of the carrier state in humans.
AB  - In our experimental model of oral candidiasis in the CD1 mouse, the primary
      infection showed reproducible Candida overgrowth kinetics with a peak level on
      day 5 of the infection. After day 7, the population stabilized at about 300
      colony-forming units per excised mucosal tissue. The primary infection triggered
      an inflammatory response that resolved in under 8 days. At this point, the
      histological pattern of the mucosa reached a new equilibrium between recruited
      and resident mononuclear cells. The primary infection also rapidly stimulated
      cellular immunity, as measured from day 4 by a delayed-type hypersensitivity
      footpad reaction. Following a second topical challenge with Candida 30 days after
      the primary infection, the infection was barely detectable and a typical local
      delayed-type hypersensitivity reaction occurred between 24-72 h. It is proposed
      that acquired resistance, in conjunction with low-level persistence of Candida in
      our model, mimics the carrier state in sensitized humans.

PMID- 8265207
TI  - Coaggregation of oral lactobacilli with streptococci from the oral cavity.
AB  - The ability of oral lactobacilli to coaggregate with streptococci and
      actinomycetes was investigated. Of the 7 species of lactobacilli studied, only
      two were capable of coaggregation and the coaggregation was restricted to
      streptococci. Lactobacillus salivarius strains (2/4) coaggregated with
      Streptococcus salivarius, Streptococcus gordonii, Streptococcus crista and tufted
      Streptococcus sanguis II strains. Lactobacillus fermentum (2/3) coaggregated with
      S. gordonii and S. sanguis. The coaggregation between L. salivarius and S.
      salivarius, S. gordonii or tufted S. sanguis II strains was mediated by a protein
      on the surface of the lactobacilli and was not inhibited by lactose. The
      coaggregation between L. fermentum and the streptococci was mediated by protein
      on the surface of the streptococci and was inhibited by lactose.

PMID- 8265209
TI  - In vitro antimicrobial susceptibility of Porphyromonas gingivalis to
      azithromycin, a novel macrolide.
AB  - The in vitro antimicrobial susceptibility of Porphyromonas gingivalis to
      azithromycin, a new macrolide antibiotic of a new class known as azalides, was
      investigated by the agar dilution method on Brucella agar. Eighty-two P.
      gingivalis strains, 79 recent oral isolates, 1 nonoral isolate and 2 reference
      strains were included in the study. Azithromycin was highly effective against P.
      gingivalis. All strains were inhibited at 1.0 microgram/ml of azithromycin or
      less. The minimal inhibitory concentrations were 0.25 microgram/ml for 50% and
      0.5 microgram/ml for 90%. These in vitro data as well as the favorable
      pharmacokinetics of azithromycin indicate that this new oral macrolide might be a
      good candidate for future clinical trials aiming to eradicate P. gingivalis from
      refractory periodontitis.

PMID- 8265208
TI  - Mutans streptococci in caries-active and caries-free infants in Tanzania.
AB  - The occurrence of mutans streptococci species was investigated in Tanzanian
      infants aged between 1.0 and 3.5 years with rampant caries and without caries
      using biochemical and immunological techniques. These infants came from Turiani
      and Singida, where the caries prevalence for this age group was 12.8% and 1.6%
      respectively. Streptococcus mutans was found to be the only mutans streptococcal
      species. The other species, including the previously reported Streptococcus
      rattus, were not found. Consequently, the differences in caries experience
      observed between and within the two populations could not be explained by
      differences in mutans streptococcal species.

PMID- 8265210
TI  - [The first information on the biology of Philomena sibirica (Nematoda:
      Philometridae)--a cavitary parasite of whitefish].
AB  - Philomena sibirica was found in the body cavity of whitefishes in one of lakes in
      the North-West of Chukotka. Its development was studied in intermedial hosts.
      Cyclops gr. scutifer and Heterocope borealis were basic intermedial hosts of the
      nematode. The latter molted twice in the haemocoel of copepods. Three larval
      stages are described.

PMID- 8265211
TI  - [The adenosinetriphosphatases of trematodes parasitizing cattle and the effect on
      them of anthelmintic preparations].
AB  - Activities and properties of adenosine triphosphatases in mitochondrial and
      microsomal fractions of trematodes Eurytrema pancreaticum and Calicophoron ijimai
      were studied. The highest ATPase activity was observed in mitochondrial
      fractions. The effect of anthelmintic preparations on activity of enzyme was
      investigated. Trichlorophene, bitionol, oxinide, G-937 and G-1028 turned out to
      be the most effective preparations.

PMID- 8265212
TI  - [The attack distance and the range and nature of the daily flight dispersion of
      horseflies in the genus Hybomitra (Diptera: Tabanidae)].
AB  - The experiments on the capture-recapture of horse-flies of the genus Hybomitra at
      different distance from a single pasturing cow have been conducted in the Pskov
      region in fields with sections of forest. A chaotic flying away of horse-flies
      was observed; presence or absence of a direct visibility of an object did not
      influence on the number of horse-flies coming to it from a distance more than 150
      m. The search flight of horse-flies has a complicated trajectory, that increases
      the probability to find a host in 2.5 times approximately, as compared with a
      straightforward one. In the case of distance less than 50 meters a quota of horse
      flies flying towards a cow can reach 100% (this conclusion derives from the
      assumption that all horse-flies, which have discovered host, are sure to attack
      it). Mean value of daily flying about is approximately 1 km, maximum is about 2
      km.

PMID- 8265213
TI  - [The finding of larvae of the taiga tick Ixodes persulcatus (Parasitiformes:
      Ixodidae) on necrophagous piophilid flies (Diptera: Piophilidae) in the southern
      Yamal].
AB  - In course of mass collecting of necrophilous flies by means of cage traps with a
      bites of dead small mammals in South Yamal, at latitude 67 North, 3400 dipterans
      were caught and examined on mite phoresy. Among them two piophilid specimens with
      two attached Ixodes persulcatus larvae have been recovered.

PMID- 8265215
TI  - On friendship.

PMID- 8265214
TI  - Wolff's Law.

PMID- 8265216
TI  - Physical therapists.

PMID- 8265217
TI  - Diagnosis and treatment of carpal tunnel syndrome.
AB  - Carpal tunnel syndrome is a commonly occurring entrapment neuropathy of the
      median nerve at the wrist. This paper reviews the causes and functional
      manifestations of this syndrome, as well as the clinical diagnosis and
      provocative tests that may be useful in establishing it. Surgical results are
      reliably good and may now be obtained with low morbidity using a variety of
      minimally invasive techniques performed through limited incisions that involve
      less extensive exposure than the "classic" open procedure. These include flexor
      tenosynovectomy without transverse carpal ligament (TCL) division, endoscopic
      release of the TCL, and subcutaneous TCL division with a two-incision technique.
      The advantages and disadvantages of these new procedures are examined.

PMID- 8265218
TI  - Painful lumbosacral sensory distribution patterns: embryogenesis to adulthood.
AB  - When the dorsal root ganglion is irritated by any of a variety of mechanisms,
      pain is referred to the various structures innervated by that root. In many
      circumstances, this pain is specific and may be used as a diagnostic aid.
      Unfortunately, emphasis is placed on defining a dermatomal distribution; the
      existence of a myotomal or sclerotomal origin of referred pain is often
      overlooked. This review presents the embryologic, anatomic, and neurophysiologic
      etiology of referred pain from the lumbar spine.

PMID- 8265219
TI  - Posterior cruciate ligament avulsion in total knee arthroplasty.
AB  - An anatomic study was outlined to measure the strength of the posterior cruciate
      ligament after total knee arthroplasty. This interest was precipitated by a
      patient whose posterior cruciate ligament ruptured 6 months after a total knee
      arthroplasty. Six unembalmed knee specimens (three bilateral) were mounted in a
      mechanical tension-testing machine, and proximal tibial total-knee bone cuts were
      performed at successive 2 to 3 mm depths. At each level, the ligament was tested
      at physiologic tension. The posterior cruciate ligament failed at 7 to 10 mm of
      bone resected, with an average failure at 8.6 mm.

PMID- 8265220
TI  - Ligamentous anatomy of the medial carpal region.
AB  - The purpose of this study is to elucidate the ligamentous anatomy of the medial
      carpus in order to characterize the pathologic basis of pisiform subluxation
      secondary to traumatic ligament rupture. Medial carpal ligamentous anatomy has
      been studied in the past by anatomic dissection and analyzed in terms of
      comparative morphology. A review of this literature reveals that the anatomy of
      the region requires further definition. We have performed cadaveric dissections
      that reveal that the ulnar or medial carpal ligament complex is composed of three
      structures: (1) the triangular fibrocartilage, (2) the meniscus homologue, and
      (3) the ulnar collateral ligament. We conclude that the medial carpal ligament
      complex has an insertion into the pisiform bone.

PMID- 8265221
TI  - Partial scapulectomy for snapping scapula syndrome.
AB  - Snapping scapula is a relatively uncommon source of scapular pain. A survey of
      the literature reveals a variety of causes of this syndrome. In the case
      presented here, the symptoms of this syndrome were immediately and permanently
      relieved by surgical excision of scapular abnormalities and part of the medial
      scapular border.

PMID- 8265222
TI  - Cat-scratch disease mimicking rhabdomyosarcoma.
AB  - A 12-year-old boy who had injured his elbow presented with a lump in the
      epitrochlear area. Originally thought to be a hematoma, then later myositis
      ossificans, this mass was actually a lymph node with large, reactive germinal
      centers. Although stains for acid-fast bacilli, fungal organisms, bacteria, and
      cat-scratch disease were negative, serological testing for detection of
      Rochalimaea henselae organisms found evidence of cat-scratch disease. We would
      like to remind orthopaedic surgeons to consider this diagnosis in evaluating
      masses of the soft tissues of the extremities.

PMID- 8265223
TI  - Traumatic neuropathic arthropathy of the spine.
AB  - Traumatic neuropathic arthropathy of the spine is becoming more prevalent as a
      result of improvement in the medical care of patients with catastrophic
      neurological compromise. This case study discusses the etiology, pathophysiology,
      and treatment of this entity.

PMID- 8265224
TI  - Dissociation of a polyethylene liner from an acetabular cup.
AB  - A polyethylene linear dissociated from a metal acetabular shell that could not be
      removed at the time of hip revision because the hexagonal hole in its screw head
      had become rounded off. A high-speed metal cutting burr was used to remove the
      screw and allow cup revision.

PMID- 8265225
TI  - A 58-year-old woman with severe low back pain.
AB  - The following case is presented to illustrate the roentgenographic and clinical
      findings of a condition of interest to the orthopaedic surgeon. The initial
      history, physical findings, and roentgenographic examinations are found on this
      page. The clinical and roentgenographic differential diagnosis is presented on
      the following pages.

PMID- 8265226
TI  - Use of a sheathed knife in hip arthroscopy.
AB  - Use of a sheathed knife to enter the hip joint during arthroscopy is described.
      It is a safe alternative to a sharp trochar, because the blade is only deployed
      after its position is verified with imaging.

PMID- 8265227
TI  - Codman's end-result idea.

PMID- 8265228
TI  - Imaging of the knee.

PMID- 8265229
TI  - Techniques of extraction of well-fixed cemented and cementless implants in
      revision total hip arthroplasty.
AB  - Removal of well-fixed cemented and cementless components in total hip
      arthroplasty is technically demanding and requires a multitude of surgical
      techniques and tools. The wide array of modular prostheses currently in use adds
      to the complexity of this task. The authors describe the several techniques that
      facilitate extraction of well-fixed cemented and cementless total hip prostheses,
      as well as the bone cement. A working knowledge of these techniques should result
      in easier implant extraction and less bone destruction during this process.

PMID- 8265230
TI  - Use of lateral heel and sole wedges in the treatment of medial osteoarthritis of
      the knee.
AB  - The authors discuss the use of lateral heel wedges in the treatment of medial
      osteoarthritis of the knee in 121 knees in 85 patients. Follow-up was an average
      of 12 months after the insertion of the wedge. Patients' roentgenograms were
      graded according to the Ahlback classification, and various improvements were
      noted. Overall, 38% of patients improved to a Hospital for Special Surgery pain
      score of 25 or 30, which corresponds to an excellent result from total knee
      arthroplasty. Fifty percent of patients improved to a pain score of 20 or higher,
      which corresponds to a good result from total knee arthroplasty. The patients
      with milder osteoarthritis received greater pain relief. However, even patients
      with complete loss of joint space and bony erosion showed some improvement. It
      appears that the use of lateral wedges has a place in the conservative treatment
      of medial osteoarthritis.

PMID- 8265231
TI  - Piriformis abscess mimicking a hip pyarthrosis.
AB  - Joint sepsis and osteomyelitis often give a confusing clinical picture in
      children because of the prevalent use of oral antibiotics for otolaryngeal
      disease, resulting in partially treated musculoskeletal infections. Unusual sites
      of infection must be considered when the patient does not respond to standard
      treatment. Recent scanning techniques can be useful in resolving this dilemma.

PMID- 8265232
TI  - Primary bone malignancies in pregnancy. A report of four cases.
AB  - Primary malignant bone tumors are rarely associated with pregnancy. Because of
      the rare nature of the condition, the relevant literature available is scant,
      providing limited information to the clinician about its management. Common
      management problems stem from delayed diagnosis and the limitations on the use of
      routine therapeutic modalities (eg, radiation and chemotherapy) during pregnancy.
      The cases presented include two cases of Ewing's sarcoma, one case of
      osteosarcoma, and one malignant fibrous histiocytoma that is thought to be
      multicentric in origin. Three of these tumors involved the scapula. The patients'
      social customs and general medical ignorance significantly affected the outcome
      of these cases.

PMID- 8265233
TI  - A 43-year-old woman with right hip pain.
AB  - Although tuberculous arthritis is currently uncommon in the United States, the
      hip joint is a common location. Tuberculous arthritis usually presents as a mild,
      slowly progressing process. It often involves a single joint. Radiological
      findings include osteopenia of the involved joint, soft tissue swelling, bone
      destruction without evidence of bone formation, and sequestrum formation. Several
      conditions should be considered in the differential diagnosis. The detailed
      roentgenographic appearances and many of the differential diagnoses are included
      in this paper. Final diagnosis is made by positive culture results or finding the
      bacillus histologically.

PMID- 8265234
TI  - A method for removing an incarcerated rod.
AB  - Occasionally during the insertion of an intramedullary (IM) rod, the rod becomes
      incarcerated, resistant to attempts to either advance or withdraw the nail.
      Infrequently, available equipment for withdrawal fails, and conventional methods
      for retrieval of the nail do not work. Such a situation is described, and a
      solution to the problem is offered.

PMID- 8265235
TI  - CEA tissue staining in colorectal cancer patients--correlation with plasma CEA,
      histology and staging.
AB  - To study the expression of tissue carcinoembryonic antigen (CEA) by
      immunoperoxidase staining in colorectal adenocarcinomas and its relation with
      preoperative serum CEA and clinicopathological parameters, we studied 85
      unselected patients who underwent resective surgery for colorectal
      adenocarcinomas and were followed up for a mean of 66 mths. All tumors except 2
      showed positive staining for CEA. The staining pattern was classifiable into 4
      types: apical, cytoplasmic, basolateral and stromal, according to the predominant
      sites of staining. We found a significant positive correlation between tissue CEA
      staining pattern and preoperative plasma CEA. Plasma CEA levels were higher when
      tumor cell staining extended to basolateral regions of the cells and into stromal
      tissues rather than restricted to apical and cytoplasmic regions (p = 0.012).
      Furthermore, tissue CEA staining also correlated positively with vascular
      invasion by tumor cells (p = 0.046), with basolateral and stromal types
      associated with more frequent vascular invasion than apical and cytoplasmic
      types. This was in contrast to the preoperative CEA which did not correlate with
      vascular permeation. We speculate that tissue CEA staining is useful in
      indicating possible vascular invasion even at early stage whereas vascular
      invasion by a larger tumor bulk or even tumor metastases may be necessary to
      produce an increased plasma CEA level that is detectable. On the other hand,
      preoperative plasma CEA had a strong, positive relationship with tumor stage and
      mortality (p < 0.001 for both). Preoperative CEA was higher in tumors showing
      moderate and poor differentiation, although it did not reach statistical
      significance (p = 0.068), whereas tissue CEA staining had no correlation with
      tumor differention.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265236
TI  - Flucloxacillin induced liver disease: histopathological findings at biopsy and
      autopsy.
AB  - The histological appearances of liver biopsies of 13 patients who developed
      cholestasis following courses of flucloxacillin are presented. In most of the
      cases jaundice and pruritus were protracted and in nearly all cases liver
      function tests are yet to return to normal after mean follow-up of 18 mths. One
      patient died after 7 mths of jaundice and another shows clinical evidence of
      secondary biliary cirrhosis. Biopsies typically showed hepatocellular and
      canalicular bile stasis with minimal or no hepatitis. Mild portal fibrosis and a
      patchy portal lymphocytic infiltrate were usually present. In 4 cases bile ducts
      were reduced in number and in 6 cases reduced in size. Bile duct epithelium
      showed degenerative changes but only occasional infiltration by inflammatory
      cells. Ductular proliferation was quite variable and in some cases--most
      noticeably the fatal case--was inconspicuous despite depletion of bile ducts. The
      appearances suggested damage not only of hepatocytes but also of bile ducts and
      proliferating ductules. This may explain the prolonged and occasionally
      irreversible hepatic disease associated with the use of flucloxacillin.
      Flucloxacillin should be included amongst the causes of vanishing bile duct
      syndrome.

PMID- 8265237
TI  - Adult polycystic kidney disease in Hong Kong Chinese: an autopsy study.
AB  - To appraise the frequency, clinical features and prognosis of adult polycystic
      kidney disease (APKD) in Hong Kong, 41 Chinese patients who had an autopsy
      diagnosis of APKD were studied retrospectively. The APKD patients constituted
      0.295% of 13,890 (or one in 339) autopsies performed during the study period
      (1964-1991). The frequency of APKD in autopsied populations in Western countries
      varies from one in 261 to one in 1,019 with an average of one in 503. Nineteen
      (46%) patients reached end-stage renal disease (ESRD) at the time of death.
      Ruptured berry aneurysm caused death in 3 patients while 3 others had spontaneous
      intracerebral hemorrhage. Left ventricular hypertrophy was found in 24 (59%)
      patients. Polycystic liver was present in 26 (63%) patients. This frequency was
      higher than the 4% to 60% (average 47%) reported in similar studies conducted in
      Western countries. The probability of patients being alive and without ESRD,
      estimated using a life table analysis, was 83%, 54%, 32% and 12% by the age of
      40, 50, 60 and 70 respectively. No difference in frequency, clinical features and
      survival between male and female APKD patients could be demonstrated.

PMID- 8265238
TI  - Pseudocysts of the adrenal gland.
AB  - Three cases of pseudocysts or hemorrhagic cysts of the adrenal gland were
      encountered in female patients who presented with loin pain. The adrenalectomy
      specimens contained cystic structures; 2 had fibrous walls containing organizing
      blood clot, the remaining lesion was thin walled and contained blood stained
      fluid. Fat, normal adrenal cortical tissue and calcification were found within
      the cysts. These lesions (arising from vascular anomalies) require separation
      from hemorrhagic adrenal neoplasms. Awareness of adrenal pseudocysts and careful
      attention to the histological features aids this distinction.

PMID- 8265239
TI  - Sudden death in pregnancy from congenital malformation of the coronary arteries.
AB  - We report the case of a 40 yr old previously healthy woman who died suddenly
      during her second pregnancy from unusual coronary artery anomalies. The left
      anterior descending coronary artery arose from the above of the right sinus of
      Valsalva 1.1 cm above the ridge in the aorta and coursed behind the pulmonary
      valve before it dipped deeply into the myocardium of the interventricular septum.
      The left circumflex coronary artery was hypoplastic. The right coronary artery
      arose also from above the right sinus of Valsalva 1.1 cm above the ridge in the
      aorta but was otherwise normal. A fourth small coronary artery arose between the
      origins of the left anterior descending and right coronary artery and supplied
      the outflow tract of the right ventricle. Mild fibrosis was present in the
      interventricular septum. The rest of the autopsy examination was unremarkable.
      Such combination of coronary artery anomalies causing sudden unexpected death in
      a pregnant woman have not previously been reported.

PMID- 8265240
TI  - Primary small cell carcinoma of the pancreas.
AB  - A 59 yr old male presented with abdominal pain and jaundice. CT scan showed a
      tumor in the pancreas with secondaries in the liver, peri-pancreatic lymph nodes,
      vertebral bone marrow and subcutaneous tissue of the neck together with a
      cervical lymph node. The patient died after 2 wks and autopsy revealed complete
      replacement of the pancreas by tumor. Careful dissection of both lungs failed to
      show any tumor. A diagnosis of primary small cell carcinoma of the pancreas was
      made. Review of the literature indicates that this type of carcinoma accounts for
      about 1% of all pancreatic cancers and is commoner in elderly males who have a
      history of cigarette smoking. There is usually a rapid progression of disease and
      widespread dissemination, especially if untreated. Some success has been obtained
      with chemotherapy.

PMID- 8265241
TI  - Fetal glial allograft in the endometrium: case report of a recurrent pseudo
      tumor.
AB  - A 32 yr old woman presented with intermittent intermenstrual bleeding, 7 mths
      after a first trimester termination of pregnancy. Diagnostic curettages at that
      time and 5 mths subsequently, both produced voluminous curettings, composed of
      mature glial tissue. Symptoms did not abate and, at hysterectomy, a discrete
      nodule of endometrial gliomatosis 18 mm in diameter was found, partly sequestered
      in a mural defect associated with an old anterior lower segment cesarian section
      scar. The glial tissue was demonstrated to retain histological viability over an
      8 mths period since the first diagnostic curettage and 15 mths since the presumed
      pregnancy of origin.

PMID- 8265242
TI  - Aggressive angiomyxoma of the vulva with an unusual vascular finding.
AB  - We report the first documented Malaysian case of aggressive angiomyxoma (AAM) of
      the vulva. A 56-yr-old woman of Indian ethnic origin presented with a vulval
      lesion which was clinically mistaken for a Bartholin's cyst. The lesion was
      surgically excised and a diagnosis of AAM was made histologically. Of particular
      interest was the finding of foamy and mononuclear inflammatory cells and fibrin
      in the walls of most of the lesional blood vessels. The patient recovered
      uneventfully and remains without tumor recurrence at the time of writing 37 mths
      after initial presentation.

PMID- 8265243
TI  - Test and teach. Number seventy-two. Diagnosis: Bacillary angiomatosis.

PMID- 8265244
TI  - Test and teach. Number seventy-three. Diagnosis: Alexander's disease.
AB  - Alexander's disease is a progressive degenerative neurological disorder
      developing in early childhood which is characterized by accumulation of Rosenthal
      fibres throughout the cerebral white matter. These fibres are composed of glial
      fibrillary acidic protein and ubiquinated alpha beta crystallin. The absence of
      atypia, increased cellularity, mitotic activity or necrosis in biopsy material
      allows differentiation from neoplasia glial processes. Clinical features
      suggestive of the diagnosis include progressive mental retardation with an
      increase in head circumference.

PMID- 8265245
TI  - Expression of the pS2 gene in breast cancer--a comparison of pS2 protein
      radioimmunoassay and immunohistochemistry.
AB  - pS2 expression was studied in a series of 82 primary breast carcinomas using and
      comparing a radioimmunoassay (RIA) technique and immunohistochemistry (IPOX).
      There was close correlation of the results obtained with each technique. Accurate
      and reliable determination of pS2 status in breast cancer can be made on the
      basis of immunohistochemistry using formalin fixed paraffin embedded sections.
      Immunohistochemical determination of pS2 status may be used in situations where
      the RIA technique cannot be applied, i.e. instances when fresh tumor tissue is
      not available.

PMID- 8265246
TI  - Nuclear DNA content of human breast carcinoma: a comparison of results obtained
      by microspectrophotometry and flow cytometry of paraffin embedded tissue.
AB  - This study compares 2 techniques for estimating the nuclear DNA content of tumor
      cell lines: (i) static cytometry of smears taken from fresh tissue and (ii) flow
      cytometry of cells extracted from paraffin embedded tissue. Parallel
      determinations of DNA content, using both techniques, were made on samples of
      tissue taken from 130 female patients with breast carcinoma. Using a simple
      classification into diploid and non-diploid groups, the 2 techniques yielded
      discrepant results in 11% of cases. The most frequent causes of disagreement were
      (a) the inability of static cytometry to distinguish between a diploid and a near
      diploid peak and (b) for flow cytometry, the difficulty of determining whether a
      minor peak in the tetraploid region represented the G2 peak of a diploid cell
      line or the G0/G1 peak of a tetraploid cell line. If it is deemed necessary to
      accurately assess ploidy status, flow cytometry on paraffin embedded tissue,
      using modern statistical programmes, would seem to be most practical for routine
      use, but some neoplasms, particularly those with an equivocal ploidy peak in the
      tetraploid range by this method, will require static cytometry to accurately
      assess nuclear DNA content. Using this approach, it appears that the disagreement
      between the 2 techniques would be less than 5%.

PMID- 8265247
TI  - Endothelium in the aorta and ilio-femoral arteries proximal to femoral
      arteriovenous fistulae in rabbits.
AB  - The endothelium and underlying internal elastic lamina of the aorta and ilio
      femoral arteries from 15 rabbits with femoral arteriovenous fistulae (2 to 92
      days postoperatively) and 3 rabbits with control femoral arteriotomies were
      examined using the en face technique and scanning electron microscopy. The
      rapidity of development of the tears in the internal elastic lamina of the
      muscular ilio-femoral arteries was greater than in fistulae involving the elastic
      common carotid artery. The elastic tissue tears appeared to have a predilection
      for certain anatomical regions possibly related to regions of specific
      hemodynamic stress. A few tears were observed in the aorta near the origin of the
      renal arteries. Initially the elastic tissue tears in the afferent ilio-femoral
      arteries were longitudinally orientated and the endothelium overlying the elastic
      tissue tears soon exhibited increased cell density relatively restricted to the
      floor of the tears. This cellular pattern was similar to that in the carotid
      jugular fistulae. With time the endothelium assumed a more conventional
      morphology.

PMID- 8265248
TI  - Pulmonary inflammation and fibrosis following subacute inhalational exposure to
      silica: determinants of progression.
AB  - To evaluate components of the pulmonary cellular response to inhaled silica that
      might be determinants of progression to fibrosis, we developed a model of the
      early stages of chronic human silicosis. Groups of mice were subacutely exposed
      either to alpha-quartz or to nonfibrogenic titanium dioxide dust as a control.
      Induction of lesions by inhaled silica was dependent upon the size distribution
      and dose of the particles. A novel observation was that low intensity exposure to
      silica evoked reversible inflammatory lesions that were characterized by focal
      aggregation of particle-laden alveolar macrophages near terminal airways. In
      contrast, higher intensity exposure elicited progressive pulmonary inflammation,
      including a significant perivascular influx of T-lymphocytes early in the
      response. The airspace inflammatory lesions exhibited a statistically significant
      decline in numerical density over time. Meanwhile, deposition of collagen was
      observed at perivascular locations, which were anatomically distinct from the
      initial foci of inflammation, and the numerical density of fibrotic lesions
      increased significantly with time. We speculate that this pattern of response
      might be related to alveolar clearance mechanisms being overwhelmed, followed by
      translocation and sequestration of particles in the interstitium, subsequently
      leading to T-lymphocyte recruitment and ultimately to the development of
      fibrosis.

PMID- 8265249
TI  - Apolipoprotein(a) and atherogenesis.
AB  - Lipoprotein(a) (Lp(a)) consists of a unique apolipoprotein, apolipoprotein(a),
      (apo(a)) linked by a disulphide bridge to apolipoprotein B of low density
      lipoprotein (LDL). Apo(a) is homologous with plasminogen and exhibits genetic
      polymorphism with the commoner phenotypes due to larger forms being associated
      with lower plasma levels and the less common phenotypes associated with smaller
      forms and higher plasma levels. The later are more common in patients with
      macrovascular disease. In a study of 6448 patients with established coronary
      heart disease we found that 43% had apo(a) levels above 300 units/litre and 10%
      had levels above 1000 units/litre and a geometric mean of 201 units/litre in
      contrast to 140 normal controls in whom 25% exceeded 300 units/litre, 1% exceeded
      1000 units/litre and the geometric mean was 107 units/litre. Amongst patients
      with cholesterol levels < 5.5 mmol/L undergoing coronary artery surgery were
      patients with low HDL levels and raised apo(a) levels who would not be identified
      in screening focusing primarily on total cholesterol. In patients with both
      insulin dependent and non insulin dependent diabetes mellitus those with
      microalbuminuria or albuminuria (known to be at high risk for macrovascular
      disease) had apo(a) levels comparable to non diabetic patients with coronary
      artery disease while diabetic patients without microalbuminuria had normal levels
      of apo(a). It is likely that apo(a) has a role in the accelerated macrovascular
      disease in diabetic patients with renal disease.

PMID- 8265250
TI  - A variant of gelatinous transformation of marrow in leukemic patients post
      chemotherapy.
AB  - A variant of gelatinous transformation of marrow was described in leukemic
      patients post-chemotherapy. This lesion was found in 8 out of 1833 post
      chemotherapy bone marrows from 429 patients with leukemia. Histologically, this
      variant form was identical to the classical gelatinous transformation except for
      the absence of fat atrophy. In marrow smears, mucoid strands were seen between
      marrow particles and oriented along the direction of spread. In clot and trephine
      sections, an eosinophilic ground substance was widespread, filling out spaces
      around the fat cells, which occupied the normal proportion of marrow space. At
      high magnification, this ground substance appeared granular and fibrillary, a non
      specific feature which could also be seen in fibrin clot commonly found in marrow
      sections. This eosinophilic ground substance, however, can be distinguished from
      fibrin clots by positive staining with Alcian Blue (pH 2.3) and inhibition of the
      staining after treatment with hyaluronidase. Clinically, in contrast to the
      classical form, this variant form of gelatinous transformation was acute in
      onset, transient, and associated with chemotherapy but not with cachexia.

PMID- 8265251
TI  - The myelodysplastic syndromes: diagnostic criteria and laboratory evaluation.

PMID- 8265252
TI  - The regulation of IgG4. 1. An immunoassay to detect bee venom specific IgG4
      subclass levels.
AB  - Serum IgG consists of 4 subclasses designated IgG1-4. IgG subclasses have
      differing structures and different functions. The levels of antigen specific
      immunoglobulin in each of the subclasses is difficult to quantitate accurately
      but may be of significant diagnostic and therapeutic value. IgG4 constitutes
      approximately 4% of total IgG level in the serum. We describe an immunoassay
      which is highly sensitive and specific for IgG4 directed against bee venom. The
      assay can be performed in a routine diagnostic laboratory enhancing its value as
      a clinical tool. It is potentially useful in identifying patients who fail to
      respond to standard immunotherapy with bee venom. This immunoassay format can
      also be adapted to other antigens.

PMID- 8265253
TI  - Osteomyelitis due to Mycobacterium haemophilum in a patient with AIDS.
AB  - A case of osteomyelitis resulting from infection with Mycobacterium haemophilum
      in a patient with the Acquired Immunodeficiency Syndrome (AIDS) and Hodgkin's
      disease is described. The clinical features and response to therapy are examined
      and compared to previous reported cases. Mycobacterium haemophilum infection in
      immunocompromised patients usually results in cutaneous lesions but osteomyelitis
      may be the presenting feature. Tissue samples should be obtained early for
      microbiological examination and treatment should consist of surgical debridement
      and appropriate antimicrobial therapy.

PMID- 8265254
TI  - M-6 endocarditis: report of an Australian case.
AB  - Neisseria elongata subsp. nitroreducens (formerly CDC group M-6) is a newly
      recognized cause of particularly destructive endocarditis, frequently requiring
      valve replacement. We describe an Australian case of endocarditis caused by this
      organism, summarizing the clinical and microbiological features of this rarely
      isolated subspecies.

PMID- 8265255
TI  - Rapid identification of mycobacteria by the Gen-Probe Accuprobe system.
AB  - Chemiluminescent acridinium ester-labelled (AE)-DNA probes (Gen-Probe, Inc., San
      Diego, Calif.) for the identification of Mycobacterium tuberculosis complex
      (MTBC) and the M. avium-M. intracellulare complex (MAC) were evaluated using 184
      mycobacterial isolates cultured in BACTEC 12B vials (Becton Dickinson and Co.,
      Towson, Md.). A 1.5 mL aliquot from BACTEC 12B vials containing acid-fast bacilli
      and a Growth Index of > 200 was concentrated 15-fold using a centrifugation step
      prior to performing the test procedure. When 184 mycobacterial isolates were
      tested (42MTBC/142 nontuberculous mycobacteria) using the AE-MTBC probe, there
      was 100% sensitivity and specificity when compared with conventional
      identification procedures. Criteria for using the AE-MAC probe were defined to
      optimize results whilst minimizing laboratory costs. Ninety-one (64%) of AE-MTBC
      probe negative isolates failed to meet selection criteria and were not tested.
      When 51 (36%) of the AE-MTBC-probe negative mycobacterial isolates were tested,
      the AE-MAC probe was found to be 88% sensitive and 100% specific. The non
      isotopic Gen-Probe test is a rapid and practical alternative to current
      procedures for differentiation of mycobacteria.

PMID- 8265257
TI  - Reply to J. H. Maynard and J. Hayman's "A case for revival".

PMID- 8265256
TI  - Teaching pathology at the University of Auckland School of Medicine.

PMID- 8265258
TI  - High titre ANA in Henoch-Schonlein syndrome.

PMID- 8265259
TI  - Cefprozil breakpoint.

PMID- 8265260
TI  - Conjunctivitis treatment.

PMID- 8265261
TI  - Conjunctivitis treatment.

PMID- 8265262
TI  - Tuberculosis: shades of AIDS.

PMID- 8265263
TI  - Current epidemiology of tuberculosis.
AB  - After years of decline, tuberculosis has become an increasing cause of morbidity
      and mortality in the United States. Chronic problems of poverty, homelessness,
      substandard housing, and poor access to health care have combined to help
      maintain a reservoir of infected persons. The addition of HIV-associated
      immunodeficiency has allowed many of these infected individuals, whose infections
      ordinarily would have remained dormant, to develop tuberculosis at younger ages.
      In addition, increasing numbers of cases of tuberculosis are being identified
      among young foreign-born adults from countries of high tuberculosis prevalence.
      Transmission from these young adults has occurred in increasing numbers to
      children. These children form an enlarging pool of infected persons that will
      continue the cycle of tuberculous infection and disease for future generations.
      Renewed emphasis and resources need to be placed on tuberculosis, particularly in
      the public health sector. Only in this manner will early detection and treatment
      of those with infection and disease occur and the cycle of tuberculosis be
      broken.

PMID- 8265264
TI  - Prevention and public health aspects of tuberculosis.

PMID- 8265265
TI  - The tuberculin skin test.

PMID- 8265266
TI  - The clinical presentation of tuberculous disease in children.

PMID- 8265267
TI  - Treatment of tuberculous infection and disease.

PMID- 8265268
TI  - Flexible fiberoptic bronchoscopy in children on extracorporeal membrane
      oxygenation.
AB  - Bleeding is one of the most feared complications of veno-arterial (V-A)
      extracorporeal membrane oxygenation (ECMO), and is also a potential complication
      of flexible fiberoptic bronchoscopy (FFB). We retrospectively reviewed 14
      patients who underwent FFB procedures with bronchial washings (BW) and
      bronchoalveolar lavage (BAL) to evaluate the safety of this procedure in children
      on ECMO. Standard FFB with BAL/BW technique was used after stabilization on ECMO.
      Three patients underwent two procedures each, and one patient underwent three,
      for a total of 19 procedures. No significant complications, such as bleeding have
      occurred. Three patients required additional ECMO support shortly after FFB.
      After the 16 procedures done for atelectasis, seven patients improved
      radiographically, three had increased opacifications, and six were unchanged. The
      remaining three patients had suspected pulmonary infections, and in each,
      therapeutic decisions were guided by the BAL results. Lung compliance was
      unchanged or improved after 11 of 13 procedures. We conclude that FFB with BAL/BW
      in children on ECMO is safe and may benefit certain patients.

PMID- 8265269
TI  - International comparison of asthma prevalence in children: Australia,
      Switzerland, Chile.
AB  - The aim of the study was to determine if the prevalence of symptoms suggestive of
      asthma in school-age children was similar in three countries with differing
      language and culture. To answer this question, we used the same instrument,
      translated appropriately, for schoolchildren in Melbourne, Australia, St. Gallen,
      Switzerland, and La Serena, Chile. A three page respiratory symptoms
      questionnaire was issued to schools for distribution to children for completion
      by parents and return to the school. Three age groups were selected for study,
      based on the average age of the school grade. Grades were used with average ages
      of 7, 12, and 15 years, respectively. A total of 26,628 questionnaires were
      issued to parents (Australia, 10,981; Switzerland, 4,464; Chile, 11,183). The
      response rates for each country were 89% for Australia, 97.5% for Switzerland,
      and 71% for Chile. The prevalence of wheezing in the last 12 months for 7 year
      olds was 23.1% in Melbourne, 7.4% in St. Gallen, and 26.5% in La Serena; for 12
      year olds it was 20.9% in Melbourne, 6.0% in St. Gallen, and 21.1% in La Serena;
      for 15 year olds it was 18.6% in Melbourne, 4.5% in St. Gallen, and 17.7% in La
      Serene. A history of wheezing was more common in boys than girls at age 7 in
      Melbourne and St. Gallen, but not La Serena. This difference was less at age 12
      and was not seen at age 15. Among those who had reported wheezing in the last 12
      months, bronchodilator use was reported by 83% (1,611/1,948) from Melbourne, 46%
      (118/259) from St. Gallen, and 47% (538/1,140) from La Serena.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8265270
TI  - Predictive value of pulmonary function testing during pulmonary exacerbations in
      cystic fibrosis.
AB  - The optimal duration of therapy for acute exacerbations of cystic fibrosis (CF)
      has not been defined, and the utility of serial pulmonary function testing in
      predicting the duration of therapy has yet to be established. In a review of 90
      pulmonary exacerbations of 39 patients with CF requiring hospitalization, we
      found that 72% of the patients recovered following 2 weeks of intravenous
      antibiotics and aggressive chest physiotherapy, and that 28% required an extended
      third week of therapy. Recovery was delayed in patients with more severe chronic
      pulmonary disease, but the rate of improvement was independent of the degree of
      pulmonary deterioration with the acute exacerbation. A 40% recovery of FEV1 at 1
      week was found to correlate significantly with the duration of hospitalization in
      the 90 patients. When prospectively applied to a second series of consecutively
      hospitalized patients with CF, 25/28 patients admitted for 2 weeks demonstrated >
      40% improvement in FEV1 at 1 week, as compared to 5/10 patients subsequently
      treated for > or = 3 weeks (P = 0.030). The predictive values for 2- or 3-week
      hospitalizations with 1-week interval recovery of > 40% or < or = 40% in FEV1
      were 79% and 62%, respectively. These findings suggest that the response to
      intensive therapy in CF exacerbations is variable and that improvements in
      pulmonary function after 1 week of therapy may be used to predict the subsequent
      duration of therapy in the majority of CF patients with pulmonary exacerbations.

PMID- 8265271
TI  - Bronchial responsiveness to inhaled metabisulfite in asthmatic children increases
      with age.
AB  - Inhaled bisulfite (HSO3) aerosol produces bronchoconstriction in asthmatics but
      not in normals. This effect is probably due to local formation of SO2 which
      stimulates vagal afferents in the airway mucosa, and gives rise to
      bronchoconstriction that is partly due to a cholinergic reflex. Metabisulfite
      (MBS) produces bronchoconstriction in most adult asthmatics, but its effect in
      children has received little attention. The present study was done to assess MBS
      induced bronchoconstriction as a function of age in asthmatic children, and to
      compare MBS responsiveness with the response to inhaled metacholine (MCH), which
      is commonly used for bronchoprovocation testing. In 36 children with moderate
      asthma, selected to cover the age range between 3 and 20 years, we compared
      airway responsiveness to MBS and MCH, expressed as the provocative dose that
      causes a 20% fall in baseline forced expiratory volume in 1 sec (FEV1, PD20). We
      also measured the PD20 to MBS after pretreatment with the anticholinergic
      ipratropiumbromide, to estimate the noncholinergic component of the response.
      After bronchial provocation with MCH, a PD20 was reached in 32 children, and no
      significant relation of PD20 to age was found. A PD20[MBS] was seen in only 17
      patients, and more frequently in older children. There was a significant negative
      correlation between age and PD20[MBS]. Ipratropium pretreatment reduced the
      response to MBS in 14 of the 17 children who had a PD20[MBS]. The PD20[MBS] after
      ipratropium pretreatment was also significantly negatively related with age. This
      suggested that the increased prevalence of MBS responsiveness was due to an
      increase of the noncholinergic component of the response.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8265272
TI  - Nedocromil sodium vs. sodium cromoglycate pressurized aerosol in the prevention
      of bronchoconstriction induced by ultrasonic nebulized distilled water in
      asthmatic children.
AB  - To compare the effectiveness of nedocromil sodium (NS) and sodium cromoglycate
      (SCG), administered by metered dose inhaler (MDI) with a 700 mL holding chamber
      (Fisonair Fisons UK) in preventing bronchoconstriction induced by inhalation of
      ultrasonically nebulized distilled water (UNDW), 12 asthmatic children were
      studied in a randomized, double-blind, placebo-controlled, intrapatient study.
      Following a baseline challenge with UNDW, the protective effect of NS, SCG, or
      placebo was evaluated in each subject. Cumulative doses of delivered nebulized
      water producing a 20% fall in forced expiratory volume in 1 sec (PD20 UNDW) was
      measured. Mean (+/- SD) PD20 UNDW was 4.83 (+/- 4.84), 10.16 (+/- 7.05), 1.58 (+/
      0.5), and 15.93 (+/- 0.23) respectively, for baseline, and placebo, SCG, and NS
      treated groups. A significant (P < 0.05) protection from UNDW induced
      bronchoconstriction by NS was observed in comparison with placebo, while no such
      effect was evident when the children were treated with SCG.

PMID- 8265273
TI  - Referencing lung volume for measurements of respiratory system compliance in
      infants.
AB  - We propose a method for measurements of respiratory system compliance (Crs) in
      spontaneously breathing infants, which circumvents the potential problems
      introduced by the breath-by-breath oscillations in the end-expiratory level,
      i.e., functional respiratory capacity (FRC). Changes in lung volume (V) and
      pressure at the airway opening (P(ao)) were measured in 10 infants breathing
      through a face mask. A first brief occlusion was to establish a reference V and
      the corresponding static P(ao); a second occlusion was done at a different V,
      within the same expiration, or in the following breath. Both occlusions were
      sufficiently long for the establishment of a stable P(ao) value. From the V
      difference (delta V, where delta V was at least 20% tidal volume) and the
      corresponding difference in P(ao) (delta P(ao)) Crs was computed and averaged
      (Crs[REF.VOL.] = delta V/delta P(ao). Although, on average, the results were
      similar to those obtained by the traditional multiple occlusions technique with
      linear regression analysis of the P(ao)-V data points (Crs[MOT]), in several
      infants Crs[REF.VOL.] tended to be slightly higher than Crs[MOT]. Some
      possibilities for this discrepancy are discussed. It seems likely that breath-to
      breath oscillation in FRC may potentially lower Crs[MOT] by introducing a bias on
      the V measurement at low P(ao). We conclude that referencing V for Crs
      measurements in spontaneously breathing infants is a simple approach, which does
      not require linear regression analysis and circumvents the effects of oscillation
      in FRC.

PMID- 8265274
TI  - Measurement of breath amplitudes: comparison of three noninvasive respiratory
      monitors to integrated pneumotachograph.
AB  - Measurement of breath amplitude (BA) and similarly tidal volume (VT) in newborn
      infants is the standard for detection of apnea and hypopneas. The purpose of our
      study was to compare the accuracy for BA by three frequently utilized noninvasive
      respiratory monitors: respiratory inductive plethysmography (RIP), mercury in
      silastic strain gauges (SG), and impedance pneumography (IP). Twenty healthy full
      term infants were studied in both supine and prone postures. The RC and AB gain
      factors for RIP were obtained using qualitative diagnostic calibration (QDC)
      procedure. The electrical gain of IP was set equivalent to the BA signal of a
      pneumotachograph (PNT). The three devices were calibrated in the supine posture
      and measurements were repeated in the prone posture without changing their
      calibration factors. Compared to PNT, postural change did not significantly alter
      BA measured by RIP. The accuracy of breath-to-breath BA measurement in the prone
      posture was worse for IP and SG compared to RIP and PNT. In contrast to SG or IP,
      the accuracy of BA measurement maintained was by RIP after a postural change from
      supine to prone in fullterm newborns.

PMID- 8265275
TI  - Real time laryngoscopy with olfactory challenge for diagnosis of psychogenic
      stridor.

PMID- 8265276
TI  - Familial congenital bronchiectasis: Williams-Campbell syndrome.
AB  - Williams-Campbell syndrome was first described in 1960 as a rare form of
      bronchiectasis. Its pathogenesis is characterized by the absence or markedly
      diminished cartilage around the bronchi. Although the familial nature was
      postulated early on, only one possible familial occurrence has been reported in
      the literature. We present two family members in whom respiratory symptoms
      developed within the first year of life and were found to have histopathologic
      changes consistent with Williams-Campbell syndrome. This world lend further
      support of a developmental origin for this type of bronchiectasis.

PMID- 8265277
TI  - Costs associated with office visits for diarrhea in infants and toddlers.
AB  - We determined costs associated with diarrhea in a < 36-month-old ambulatory
      population. Children with acute diarrhea were enrolled during the rotavirus
      season at three centers. Questionnaires to assess costs of both medical and
      nonmedical factors were administered at the enrollment visit and 1 week later.
      Office computer records were reviewed to identify all visits by children with
      diarrhea during 1 year. Fifty-one patients were enrolled. The average cost per
      episode of diarrhea was $289, which included: $144, missed work; $57, office
      visits; $23, laboratory tests; $21, medications; $18, changed diet/oral
      rehydration solutions; $15, travel; $7, extra diapers; and $6, extra child care.
      During 1 year diarrhea accounted for 4% of all visits and 10% of visits among
      those < 36 months old. The annual cost at the three centers was $346,000, which
      extrapolates to $0.6 to $1.0 billion for the United States. Twenty-one percent of
      this cost was attributable to rotavirus diarrhea. We conclude that outpatient
      care for pediatric diarrhea is a major health care cost in the United States.

PMID- 8265278
TI  - Etiology of acute encephalitis in childhood in Slovenia.
AB  - The etiology of acute encephalitis was evaluated in a retrospective study of 170
      children (98 boys and 72 girls) ages 1 month to 15 years, who were hospitalized
      during a 13-year period from 1979 to 1991. The etiology was confirmed or
      considered very probable in 68% of cases. The identified etiologic agents
      included Central European tick-borne encephalitis virus (28.8%), varicella-zoster
      virus (17.0%), herpes simplex (10.0%), rubella (2.9%), mumps (2.3%), measles
      virus, Chlamydia psittaci (1.1%) and some other agents found in individual cases.
      The etiology remained unknown in 54 children (31.7%). Forty-two patients had
      encephalitis with focal neurologic signs. The most common confirmed or
      presumptive infective agent in those cases was herpes simplex virus (40.4%),
      followed by rubella (7.1%), Central European tick-borne encephalitis virus (4.7%)
      and some other agents identified in individual cases. The etiology remained
      unknown in 15 (36%) children with focal encephalitis.

PMID- 8265279
TI  - Human immunodeficiency virus 1-specific IgA capture enzyme immunoassay for early
      diagnosis of human immunodeficiency virus 1 infection in infants. NYC Perinatal
      HIV Transmission Study Group.
AB  - A simplified human immunodeficiency virus 1 (HIV-1)-specific IgA capture enzyme
      immunoassay (IgA-CEIA) was evaluated and compared with IgA-Western blot assay for
      early diagnosis of HIV-1 infection in infants born to seropositive women. A total
      of 232 coded sera collected prospectively from 70 infants were tested. All 25
      sera from 10 HIV-1-negative infants born to seronegative mothers (negative
      controls) were negative by both assays. All 111 sera from 37 seroreverting,
      uninfected infants were negative by IgA-CEIA (specificity, 100%), whereas 110 of
      111 sera were negative by IgA-Western blot assay (specificity, > 99%). Overall
      IgA-CEIA detected HIV-IgA in 20 (87%) of 23 infected infants, and IgA-Western
      blot assay detected HIV-IgA in 21 (91.3%) of 23 infants; specimen-wise agreement
      between the 2 assays was > 80%. Analysis of results by age group indicated that
      after 2 months of age both assays were equivalent with sensitivity ranging from
      60 to 80%. Quantitative data provided by IgA-CEIA suggests that the bulk of HIV-1
      IgA synthesis in most HIV-1-infected infants occurs after 2 months of age.

PMID- 8265280
TI  - Risk of infection during adrenocorticotropic hormone treatment in infants with
      infantile spasms.
AB  - We reviewed the clinical features and laboratory findings of 27 infants with
      infantile spasms treated with adrenocorticotropic hormone or prednisone during
      febrile episodes in order to evaluate the incidence of bacteremia, the risk of
      serious infection, determination of whether serious infections can be identified
      at presentation and the outcome of febrile episodes. There were 75 febrile
      episodes including 4 episodes of identified bacteremia (5.3%). Three children who
      were treated with adrenocorticotropic hormone dosage larger than recommended
      died. Leukocytosis and a differential count with many immature granulocytes
      predicted bacteremia in this population. Chest radiography was useful in
      identifying the cause of fever. The pathogens isolated were similar to those
      found in this age range. We conclude that the frequency of bacteremia in our
      patient population is similar to that observed in infants of the same age;
      however, the outcome is frequently fatal. In addition this increased mortality
      may be associated with the use of a larger dosage of adrenocorticotropic hormone
      than recommended.

PMID- 8265281
TI  - Fever and neutropenia in children with cancer: a therapeutic approach related to
      the underlying disease.
AB  - Antibiotic monotherapy is increasingly an option for the initial empiric
      treatment of febrile neutropenic cancer patients. We noted in a previous study
      that response to empiric therapy was related more to disease classification
      (solid tumors vs. leukemia) than to the regimen chosen. In the present study we
      based empiric monotherapy on the underlying disease in treating 240 episodes of
      fever and neutropenia in 145 children. Patients with leukemia or Stage III/IV non
      Hodgkin's lymphoma (higher risk group) were treated with imipenem-cilastatin,
      whereas those with solid tumors or Stage I/II non-Hodgkin's lymphoma (lower risk
      group) received ceftriaxone. The regimens were modified in 15% of lower risk and
      45% of higher risk episodes. Overall successful outcomes were obtained in 93.2%
      of the higher risk (n = 119) and 97.5% of the lower risk (n = 121) episodes. The
      two groups differed significantly in duration of neutropenia, frequency of
      positive blood cultures and superinfection and the need for modification of the
      monotherapy (P < 0.05). Empiric monotherapy based on primary disease appears to
      be safe and effective for febrile neutropenic children with cancer at our
      Brazilian institution. Further studies will be needed before these findings can
      be generalized to patient populations in other settings.

PMID- 8265282
TI  - Nosocomial adenovirus infection: molecular epidemiology of an outbreak.
AB  - Nosocomial transmission of adenovirus type 3 associated with fatalities in
      infants has not been frequently reported. This report describes the nosocomial
      spread of adenovirus types 2 and 3 among infants with bronchopulmonary dysplasia
      in a chronic (transitional) care facility. The index case developed pneumonia
      with a clinical deterioration in respiratory status 8 days after admission.
      Within the next 10 to 30 days 9 other infants and 2 health care personnel became
      ill with respiratory symptoms. Three of these 10 infants had progressive
      respiratory failure and 2 of them died. All of these infants had underlying
      chronic lung disease of bronchopulmonary dysplasia. The overall attack rate was
      30% (10 of 33). Further spread of adenovirus was prevented by using barrier
      precautions and masks while performing tracheostomy care. Adenovirus isolates
      were serotyped as Ad3 in 4 patients and 1 staff member, as Ad2 in 3 patients, and
      as a combination of Ad2 and Ad3 in 1 patient. Two fatalities were associated with
      Ad3 infection. Three isolates from 2 patients and 1 staff member were not
      available for typing. Restriction endonuclease analysis was performed on all of
      these isolates of Ad3 and Ad2. There was no genetic heterogeneity in the
      isolates, suggesting a common source.

PMID- 8265283
TI  - Detection of alpha-interferon in nasopharyngeal secretions and sera in children
      infected with respiratory syncytial virus.
AB  - We investigated the relationship between respiratory syncytial virus (RSV)
      antigen and interferon (IFN) in nasopharyngeal secretions (NPS) and sera obtained
      from 252 patients infected with RSV. A total of 146 (57.9%) of 252 patients had
      IFN in NPS with a mean titer of 28 units/ml and IFN was detected in 164 (71.6%)
      of 229 patients in the acute stage sera with a mean titer of 28 units/ml. IFN
      activities were neutralized with antiserum to IFN-alpha. RSV antigen in NPS
      decreased on Day 5 and later in parallel with the change of mean titer of IFN in
      NPS. IFN in NPS was detected in 40 to 60% of the samples with some fluctuation in
      the acute stage. Within 4 days IFN was detected in more than 70% of the sera
      whereas on Day 5 and later the IFN positivity rate decreased in sera. RSV antigen
      in NPS decreased in the older patient groups. No significant change of positive
      rate of IFN in NPS was observed in different age groups and the mean titer of IFN
      in NPS and sera did not vary with age, except in those younger than 3 months and
      older than 3 years of age.

PMID- 8265284
TI  - Amebic liver abscess in children.
AB  - Although amebic liver abscess can be a cause of significant morbidity and
      mortality in all ages, there are few reports dealing with this entity in
      children. Twenty-four children with amebic liver abscess, ages ranging between 3
      weeks and 14.5 years, were managed at the Aga Khan University Hospital, Karachi,
      Pakistan, between November, 1987, and October, 1992. The most frequent
      presentation was high grade fever and right upper quadrant pain, associated with
      tender hepatomegaly, leukocytosis and an elevated erythrocyte sedimentation rate.
      The diagnosis was confirmed by elevated indirect hemagglutination titers and
      ultrasonography of the liver. Unlike the experience in adult patients none of the
      patients had concomitant jaundice, and significant derangement of liver enzymes
      was unusual. The abscesses were likely to be solitary (22 of 24 patients). There
      were no deaths despite a mean delay of 15 days before presentation to our
      hospital. A high index of suspicion, early institution of metronidazole therapy
      and aspiration of abscesses with potential to rupture are believed to have
      contributed to the better outcome in these children when compared with results in
      previous reports.

PMID- 8265285
TI  - The complement system in host defense and inflammation: the cutting edges of a
      double edged sword.

PMID- 8265286
TI  - Congenital lymphocytic choriomeningitis virus infection in twins.

PMID- 8265287
TI  - Plasma immunotherapy in a child with acquired immunodeficiency syndrome.

PMID- 8265288
TI  - Is Haemophilus influenzae type b conjugate vaccine (meningococcal protein
      conjugate) compatible with diphtheria-pertussis-tetanus vaccine in young infants?

PMID- 8265289
TI  - Management of varicella exposures in the neonatal intensive care unit.

PMID- 8265290
TI  - Pediatrician-dependent barriers in influenza vaccine administration.

PMID- 8265291
TI  - The use of urokinase for loculated thoracic empyema in children: a case report
      and review of the literature.

PMID- 8265292
TI  - Characteristics of herpes zoster in otherwise normal children.

PMID- 8265293
TI  - Candida rugosa central venous catheter infection in a child.

PMID- 8265294
TI  - Renal tuberculosis in a child with hematuria.

PMID- 8265295
TI  - Bacterial tracheitis caused by Pseudomonas aeruginosa.

PMID- 8265296
TI  - Eosinophilic meningitis in a newborn with group B streptococcal infection.

PMID- 8265297
TI  - Rash and pruritus after a camping trip.

PMID- 8265298
TI  - Herpes simplex pneumonia: direct fluorescence microscopy as an aid in diagnosis.

PMID- 8265299
TI  - Combined immunization against hepatitis B: five-year follow-up.

PMID- 8265300
TI  - Indications for oral acyclovir in children.

PMID- 8265301
TI  - Control of jaundice in preterm newborns by an inhibitor of bilirubin production:
      studies with tin-mesoporphyrin.
AB  - BACKGROUND: Studies in vitro, in animal models, and in adult and newborn humans
      have demonstrated that certain tin(Sn)-porphyrins that competitively inhibit the
      activity of heme oxygenase, the rate-limiting enzyme in heme catabolism, reduce
      production of bilirubin and can thereby substantially diminish plasma levels of
      the bile pigment. OBJECTIVES: To assess the effectiveness of increasing doses of
      the heme oxygenase inhibitor, Sn-mesoporphyrin (SnMP), in moderating the
      development of significant hyperbilirubinemia and thus the requirements for
      phototherapy in preterm newborns. METHODS: In five randomized, blinded, placebo
      controlled trials, SnMP in increasing doses from 1 mumol to 6 mumol/kg body
      weight was administered intramuscularly in the first 24 hours of life in preterm
      newborns of 210 to 251 days gestational age. "Special blue" lamps (Phillips
      F20T12/BB) were used for phototherapy in newborns exceeding a predetermined
      plasma bilirubin concentration, irrespective of study group. RESULTS: A total of
      517 newborns were randomized in the five trials carried out sequentially over a 4
      year period. SnMP in a dose-related manner significantly ameliorated the course
      of hyperbilirubinemia in the treated newborns of all gestational ages. With a
      SnMP dose of 6 mumol/kg body weight, the mean peak incremental plasma bilirubin
      concentration was reduced by 41% and the phototherapy requirements were decreased
      by 76% compared to control subjects. Erythema observed in a few SnMP-treated
      newborns who required phototherapy was mild, transient, and without sequelae. No
      other untoward effects were observed during hospitalization or at a follow-up at
      post-term age of 3 and 18 months. CONCLUSIONS: SnMP, by inhibiting the production
      of bilirubin, substantially moderates the development of hyperbilirubinemia in
      preterm newborns. This compound and similarly acting enzyme inhibitors merit
      further clinical study as agents for controlling neonatal hyperbilirubinemia,
      particularly in neonatal populations for whom other treatment modalities are not
      available.

PMID- 8265302
TI  - Clinical features of infants with primary human herpesvirus 6 infection (exanthem
      subitum, roseola infantum).
AB  - OBJECTIVE: To clarify clinical features of patients with primary human
      herpesvirus 6 (HHV-6) infection (roseola infantum, exanthem subitum) in a large
      scale study. SUBJECTS AND METHODS: Clinical signs and symptoms were analyzed in
      176 infants in whom exanthem subitum was initially suspected and primary HHV-6
      infection was later confirmed. The infection was proved by isolation of the virus
      from blood, a significant increase in the neutralizing antibody titers to the
      virus, or both. RESULTS: The primary HHV-6 infection, which occurred throughout
      the year, was observed in 94 boys and 82 girls (mean age, 7.3 months). Fever
      developed in 98% (mean maximum fever, 39.4 degrees C) and lasted for 4.1 days.
      Macular or papular rashes appeared in 98%, on face, trunk, or both, mostly at the
      time of subsidence of the fever, and lasted for 3.8 days. Other clinical
      manifestations occurred as follows: mild diarrhea in 68%, edematous eyelids in
      30%, erythematous papules in the pharynx in 65%, cough in 50%, and mild cervical
      lymph node swelling in 31%. Twenty-six percent had bulging of the anterior
      fontanelle and 8% had convulsions. CONCLUSIONS: Clinical features of patients
      with virologically confirmed exanthem subitum were comparable with those
      described before discovery of HHV-6.

PMID- 8265303
TI  - Family history of coronary artery disease and cholesterol: screening children in
      a disadvantaged inner-city population.
AB  - BACKGROUND AND PURPOSE: Little information relating to cholesterol levels and
      screening for hypercholesterolemia in inner-city children exists. For this study,
      given the disrupted family backgrounds of many of our patients and the
      unreliability of family histories, our hypothesis was that in comparison with
      other samples, family history of coronary heart disease would be a poor screening
      tool for the identification of children with elevations in total serum
      cholesterol (TSC). SUBJECTS AND METHODS: During 15 months, more than 400
      pediatric outpatients, 2 through 14 years old, were screened for a family history
      of atherosclerotic disease. These children were attending a clinic serving a
      disadvantaged black and Hispanic population at Kings County Hospital Center.
      Nonfasting TSC levels were measured in 300 children. Positive risk for coronary
      heart disease was determined by the presence of a family history of coronary
      heart disease (defined as angina, stroke, or myocardial infarction in any parent
      or grandparent) at less than 55 years age. RESULTS: The mean TSC level was 4.27
      mmol/L SD +/- 0.85) (165.0 mg/dL [SD +/- 32.8]). The 29.4% of this population
      with a history suggestive of high risk for hypercholesterolemia had a mean TSC of
      4.48 mmol/L (SD +/- 0.971) (173.2 mg/dL [SD +/- 37.5]), and those with no risk
      history had a mean TSC of 4.18 mmol/L (SD +/- 0.750) (161.4 mg/dL [SD +/- 29.9])
      (P < .005). Use of family history of coronary artery disease as a screening tool
      had a sensitivity of 39.3%, a specificity of 74.5%, and a positive predictive
      value of 39.8% for detection of moderate hypercholesterolemia (TSC > or = 4.66
      mmol/L [180 mg/dL]). CONCLUSIONS: This population's mean TSC level did not differ
      (P > .10) from those obtained in multiple large studies of average North American
      populations, and the predictive value and sensitivity of family history as a
      screening tool was comparable, although the prevalence of a positive family
      history was greater. The findings may be due to a greater prevalence of coronary
      artery disease at a young age in these families. In this population, a positive
      risk history is an important indicator for further evaluation of these children.

PMID- 8265304
TI  - Practice parameter: the office management of acute exacerbations of asthma in
      children. American Academy of Pediatrics. Provisional Committee on Quality
      Improvement.
AB  - The American Academy of Pediatrics, and its Provisional Committee on Quality
      Improvement in collaboration with experts from the Sections on Allergy and
      Pulmonology, general pediatricians, and research methodologists have developed
      this practice parameter. This parameter is based on the work reported by the
      National Asthma Education Project of the National Heart, Lung, and Blood
      Institute. It differs by specifically addressing the treatment of acute
      exacerbations of asthma in the office setting as opposed to the emergency
      department or hospital, and by providing a rigorous analysis of the scientific
      evidence supporting some of the key recommendations in the report. The
      recommendations derive from both expert consensus and a review of the medical
      literature. A detailed discussion of the Committee selection and the methods used
      can be found in the technical report that is available from the Division of
      Quality of Care, American Academy of Pediatrics. This practice parameter is not
      intended to stand alone in the treatment of the child with asthma. It is designed
      to assist pediatricians by providing an analytic framework for the evaluation and
      treatment of acute exacerbations of asthma. It is not intended to either replace
      clinical judgment or to establish a protocol for all patients with asthma. It
      rarely will be the only appropriate approach to the problem.

PMID- 8265305
TI  - Oral immunoglobulins for treatment of acute rotaviral gastroenteritis.
AB  - OBJECTIVE: Preliminary evidence has been reported on the antirotavirus effect of
      human serum immunoglobulin administered orally. The aim was to see whether such
      treatment might be effective in rotavirus acute gastroenteritis. METHODS: A
      prospective, double-blind, placebo-controlled study was performed. Ninety-eight
      children admitted with acute gastroenteritis were enrolled and randomly assigned
      to groups A (treated) and B (control). Children in group A received a single oral
      dose of 300 mg/kg body weight of human serum immunoglobulin. Parameters of
      efficacy were clinical condition, frequency and consistency of stools, duration
      of diarrhea, duration of viral excretion, and length of hospital stay.
      Antirotaviral activity was determined in the immunoglobulin preparation by a
      specific neutralization assay. RESULTS: Seventy-one of the 98 children enrolled
      had rotaviral gastroenteritis; 36 belonged to group A. Children who received
      immunoglobulin had significantly faster clinical improvement of clinical
      condition and stool pattern than control children. Mean total duration of
      rotaviral diarrhea was 76 hours in group A and 131 in group B (P < .01). Viral
      excretion lasted 114 and 180 hours, respectively (P < .01). Hospital stay was
      significantly reduced in children in group A. Neutralizing antibodies against
      rotavirus were detected in the immunoglobulin preparation. CONCLUSION: Oral
      administration of immunoglobulin is associated with a faster recovery from acute
      gastroenteritis and should be given to children hospitalized with this illness.

PMID- 8265306
TI  - Nutrition and behavior: the legend continues.

PMID- 8265307
TI  - American Academy of Pediatrics Committee on Injury and Poison Prevention: School
      bus transportation of children with special needs.

PMID- 8265308
TI  - American Academy of Pediatrics. Committee on Infectious Diseases: Screening for
      tuberculosis in infants and children.

PMID- 8265309
TI  - American Academy of Pediatrics Committee on Child Health Financing: Medicaid
      policy statement.

PMID- 8265310
TI  - American Academy of Pediatrics Committee on Drugs: The transfer of drugs and
      other chemicals into human milk.

PMID- 8265311
TI  - Hepatitis B immunization: pediatrician's perspective.

PMID- 8265312
TI  - Prevalence of cerebral palsy: estimations, calculations and neonatal care.

PMID- 8265313
TI  - Office lab regulations vs research.

PMID- 8265315
TI  - 'New' diapers and vaginal discharge.

PMID- 8265314
TI  - Are there serious problems?

PMID- 8265316
TI  - Bilirubin and other brain cells.

PMID- 8265317
TI  - Controversies concerning vitamin K and the newborn.

PMID- 8265318
TI  - Use of nonhuman milks in the dietary management of young children with acute
      diarrhea: a meta-analysis of clinical trials.
AB  - OBJECTIVE: To assess the effects of continued feeding of nonhuman milks or
      formulas to young children during acute diarrhea on their treatment failure
      rates, stool frequency and amount, diarrheal duration, and change in body weight.
      METHODS: A total of 29 randomized clinical trials of 2215 patients were
      identified by computerized bibliographic search and review of published articles.
      Data were abstracted and analyzed using standard meta-analytic procedures.
      RESULTS: Among studies that compared lactose-containing milk or formula diets
      with lactose-free regimens, those children who received the lactose-containing
      diets during acute diarrhea were twice as likely to have a treatment failure as
      those who received a lactose-free diet (22% vs 12%, respectively; P < .001).
      However, the excess treatment failure rates occurred only in those studies that
      included patients whose initial degree of dehydration, as reported by authors,
      was severe, or that were conducted before 1985, when appropriate diarrhea
      treatment protocols were first widely accepted. Among studies of patients with
      mild diarrhea, all but one of which were completed after 1985, the overall
      treatment failure rates in the lactose groups were similar to the rates in the
      lactose-free groups (13% vs 15%). These results suggest that children with mild
      or no dehydration and those who are managed according to appropriate treatment
      protocols, such as that promoted by the World Health Organization, can be treated
      as successfully with lactose-containing diets as with lactose-free ones. The
      pooled information from studies that compared undiluted lactose-containing milks
      with the same milks offered at reduced concentration concluded that (1) children
      who received undiluted milks were marginally more likely to experience treatment
      failure than those who received diluted milk (16% vs 12%, P = .05), (2) the
      differences in stool output were small and of limited clinical importance, and
      (3) children who received the undiluted milk diets gained 0.25 SD more weight
      than those who received the diluted ones (P = .004). In addition, as with the
      previous set of studies, there were no differences in the pooled treatment
      failure rates between the respective groups in those studies of mildly dehydrated
      patients conducted after 1985 (14% vs 12%). CONCLUSIONS: The vast majority of
      young children with acute diarrhea can be successfully managed with continued
      feeding of undiluted nonhuman milks. Routine dilution of milk and routine use of
      lactose-free milk formula are therefore not necessary, especially when oral
      rehydration therapy and early feeding (in addition to milk) form the basic
      approach to the clinical management of diarrhea in infants and children.

PMID- 8265319
TI  - Secretory anti-Giardia lamblia antibodies in human milk: protective effect
      against diarrhea.
AB  - OBJECTIVE: To determine whether anti-Giardia lamblia secretory IgA (sIgA)
      antibodies in human milk protect infants from acquisition of or symptoms
      associated with Giardia infection. METHODS: One hundred ninety-seven Mexican
      mother/infant pairs were followed weekly from birth for diarrheal disease and
      feeding status. Infant stool specimens were collected weekly and were cultured
      for bacterial pathogens and tested for Giardia and rotavirus by enzyme-linked
      immunosorbent assay. Maternal milk samples were collected weekly for 1 month
      postpartum and monthly thereafter. To determine the protective effect of anti
      Giardia sIgA in milk against infection and against diarrhea due to Giardia, milk
      samples from mothers of infected infants and appropriately matched controls were
      assayed for anti-Giardia sIgA by enzyme-linked immunosorbent assay. RESULTS:
      Asymptomatic, infected infants ingested significantly (P = .046) higher amounts
      of milk anti-Giardia sIgA compared with symptomatic, infected infants. However,
      milk anti-Giardia sIgA concentrations did not differ between Giardia-infected and
      noninfected infants. CONCLUSION: The amount of anti-Giardia sIgA in human milk
      was associated with prevention of symptoms of diarrhea due to Giardia, but not
      with acquisition of the organism.

PMID- 8265320
TI  - Clinical comparison of localized intestinal perforation and necrotizing
      enterocolitis in neonates.
AB  - OBJECTIVE: To better define the prognosis of neonates with gastrointestinal
      perforation and improve their management. METHODS: We reviewed the results of
      physical examinations, laboratory results, and radiographic tests of 42 patients
      in whom gastrointestinal perforation was diagnosed in our neonatal intensive care
      unit. RESULTS: Twenty-one patients had necrotizing enterocolitis and 21 had
      localized intestinal perforation. Perinatal history, gender, race, birth weight,
      and estimated gestational age were similar for both groups. Patients with
      localized perforation were more likely to have had an umbilical artery catheter
      in place within 48 hours of perforation, to have received higher doses of
      indomethacin, to have undergone primary surgical repair, and to have survived
      until discharge from the hospital. Patients with necrotizing enterocolitis were
      more likely to have received enteral feedings and to have had a metabolic
      acidosis and leukopenia at the time the perforation was diagnosed. CONCLUSIONS:
      We conclude that localized intestinal perforation and necrotizing enterocolitis,
      although similar in the organ system they affect, are distinctly different in
      clinical correlates and outcome. The increased awareness of localized
      perforations may help those taking care of neonates to diagnose this condition
      more accurately and to discuss its implications with family members.

PMID- 8265321
TI  - Acellular and whole-cell pertussis vaccines as booster doses: a multicenter
      study.
AB  - OBJECTIVE: To compare the safety and immunogenicity of a variety of acellular
      (AC) and whole-cell (WC) pertussis vaccines combined with diphtheria and tetanus
      toxoids. METHODS: Standard enrollment and reaction forms were used at five sites,
      and serologic evaluation was performed at a single site. Nine AC (Massachusetts
      Public Health Laboratories, Biocine Sclavo recombinant pertussis toxoid [PT],
      Connaught/BIKEN, Lederle three-component, Biocine Sclavo recombinant three
      component, SmithKline Beecham three-component, Porton three-component, Takeda
      Wyeth, and Connaught multicomponent), and three WC (Connaught Laboratories,
      Lederle Laboratories, and Massachusetts Public Health Laboratories) were studied.
      All AC contained varying concentrations of PT; some vaccines also contained
      filamentous hemagglutinin (FHA), pertactin, and/or agglutinogens. RESULTS: Two
      hundred forty children, aged 16 to 21 months and 4 to 6 years, were enrolled at
      five sites. Significantly less fever, redness, swelling, pain, limp, and use of
      pain medication were noted following AC compared with WC. Significant increases
      in antibody to PT were seen following all vaccines. Significant rises in FHA
      antibody were seen following all WC and the seven AC that contained FHA.
      Postbooster PT antibody levels were similar among the AC groups, regardless of
      the amount of PT administered (between 3.5 and 25 micrograms per dose). The dose
      of FHA did not affect PT antibody response. Infants primed with WC who were
      boosted with a monocomponent PT vaccine did not manifest a significant antibody
      response to FHA. CONCLUSION: The rate of adverse reactions was not a function of
      the number of antigens or the antigen quantity in the acellular vaccines, and
      antibody responses following AC were similar or better than antibody responses
      following WC. These results support the further evaluation of these vaccines in a
      larger National Institute of Allergy and Infectious Diseases-sponsored study in
      infants.

PMID- 8265322
TI  - Cardiorespiratory recordings from infants dying suddenly and unexpectedly at
      home.
AB  - OBJECTIVE: Little is known about the mechanism of death during sudden infant
      death. To study the mechanism, we obtained data on six infants who died while on
      a memory-equipped cardiorespiratory monitor. METHODS: Waveforms of respiration
      and heart rate trend were available for five infants; an alarm log only was
      available for the sixth. These printouts were reviewed with attention to
      mechanism and time to death. RESULTS: All infants were born prematurely;
      autopsies reported the cause of death as sudden infant death syndrome in three
      cases and bronchopulmonary dysplasia in the others. Bradycardia, which played a
      more prominent role than central apnea, was preceded by tachycardia in two
      deaths. Resuscitation occurred within 1 minute in four cases; no response to
      alarms occurred in the other two cases, apparently because the parents were
      desensitized by prior meaningless alarms. Five patients died within 20 minutes,
      whereas one death due to sudden infant death syndrome was prolonged. CONCLUSION:
      Bradycardia is an important feature in all six of these infant deaths. Although
      its etiology is unknown, hypoxemia or obstructive apnea may precede bradycardia.
      Home monitors equipped to detect these possible antecedents will yield further
      insight into sudden infant death.

PMID- 8265323
TI  - Vigintiphobia, unbound bilirubin, and auditory brainstem responses.
AB  - OBJECTIVE: The management of nonhemolytic hyperbilirubinemia in term newborns is
      controversial. To evaluate the usefulness of serum unbound bilirubin
      concentrations (UBCs) in the management of hyperbilirubinemia, we compared the
      concentrations with abnormal auditory brainstem responses (ABRs). METHODS: ABRs
      and serum UBCs in 37 hyperbilirubinemic term newborns (total bilirubin
      concentrations [TBCs] > or = 20 mg/dL and direct bilirubin concentrations < 2
      mg/dL) were measured before treatment with either phototherapy or exchange
      transfusions. Eight of these newborns had blood incompatibilities. These
      hyperbilirubinemic newborns were divided into three groups according to the
      findings of ABR: group A, normal ABR (n = 18); group B, prolonged latency of wave
      I only (n = 8); and group C, prolonged interpeak latency of wave I-III/I-V and/or
      poor amplitude (n = 11). RESULTS: The peak TBC was significantly different
      between groups A and C (22.8 +/- 2.2 mg/dL and 25.4 +/- 2.5 mg/dL, respectively;
      P < .05), though there were no differences between groups A and B and between
      groups B and C. The peak UBCs in groups B (1.27 +/- 0.7 micrograms/dL) and C
      (1.34 +/- 0.37 micrograms/dL) were significantly higher than in group A (0.78 +/-
      0.26 microgram/dL) (P < .05 and P < .01, respectively), though there was no
      significant difference in the peak UBC between groups B and C. Abnormal ABR
      findings were more clearly associated with the level of UBC at 1.0 microgram/dL
      than that of TBC at 23 mg/dL by multiple logistic regression analysis (odds ratio
      = 16.6, P = .0026, vs 4.2, P = .1272). CONCLUSIONS: These results suggest that
      measuring UBC may help in evaluating the possible risk of bilirubin
      encephalopathy in full-term newborns when there is vigintiphobia (fear of 20).

PMID- 8265324
TI  - Interleukin-6: a sensitive parameter for the early diagnosis of neonatal
      bacterial infection.
AB  - OBJECTIVE: Early recognition is important for the successful treatment and
      outcome of neonatal infections. As interleukin-6 (Il-6) plays a critical role in
      the induction of C-reactive protein (CRP) synthesis in the liver, it was
      hypothesized that this cytokine could be detected earlier in blood than the CRP
      during the course of bacterial infection. DESIGN: In a prospective study of 298
      newborns who were admitted to the nursery unit, CRP levels, blood cell count with
      differential, and Il-6 levels were determined at the time of admission and 24
      hours after admission. Seventy-six newborns were excluded from the study because
      of incomplete or incorrect blood sampling. RESULTS: The remaining 222 newborns
      were assigned to one of five groups: 11 newborns with blood culture-positive
      sepsis (sensitivity of Il-6 on admission 73%), 15 newborns with clinical sepsis
      (sensitivity of Il-6 on admission 87%), 41 newborns with infection (sensitivity
      of Il-6 on admission 68%), and 54 newborns without clinical and laboratory
      evidence of infection (specificity 78%). The remaining 101 newborns were defined
      as a mixed group because the diagnosis of neonatal infection could not clearly be
      made. Seventy-five percent of infected newborns had negative Il-6 levels 24 hours
      after admission. Of the 18 infected newborns with negative Il-6 levels on
      admission, 10 newborns had elevated CRP levels, suggesting that Il-6 was already
      negative because of the short half-life of Il-6. Sensitivity of Il-6 in CRP
      negative newborns on admission was 100% in newborns with blood culture-positive
      and clinical sepsis. Il-6 was more sensitive than CRP in infected newborns on
      admission (73% vs 58%). CONCLUSION: Il-6 is a sensitive parameter for diagnosing
      neonatal bacterial infection. The combination of CRP and Il-6 seems to be the
      ideal tool for the early diagnosis of neonatal infection.

PMID- 8265325
TI  - Serum C-reactive protein, erythrocyte sedimentation rate, and white blood cell
      count in acute hematogenous osteomyelitis of children.
AB  - OBJECTIVE: The aim of this prospective study was to compare the clinical value of
      the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white
      blood cell (WBC) count in diagnosis and follow-up of acute hematogenous
      osteomyelitis in children. DESIGN: Forty-four children aged 2 weeks to 14 years
      with bacteriologically confirmed acute hematogenous osteomyelitis were examined.
      Staphylococcus aureus was responsible in 39 cases (89%), Haemophilus influenzae
      type b in 3 cases (7%), pneumococcus in 1 case (2%), and a microaerophilic
      streptococcus in 1 case (2%). ESR was measured at the time of admission and on
      days 3, 5, 7, 10, 14, 19, and 29 of treatment, and CRP was measured on the same
      days as ESR but also on days 2, 9, 12, 17, and 23. WBC count was examined at the
      time of admission and on days 5, 10, 19, and 29. RESULTS: ESR was elevated (> or
      = 20 mm/h) initially in 92% of the cases; the mean value was 45 mm/h, and the
      peak values (mean 58 mm/h) were reached on days 3 to 5. After this the levels
      slowly returned to normal in approximately 3 weeks (mean 18 days). CRP was
      elevated (> 19 mg/L) at the time of admission in 98% of the cases, the mean value
      being 71 mg/L. The peak CRP value was reached on day 2 (mean 83 mg/L). The
      decrease was very rapid, normal values being reached within a week (mean 6.9
      days). The WBC count was a poor indicator of acute hematogenous osteomyelitis,
      since only 35% of the children had leukocytosis (WBCs > 12 x 10(9)/L) at the time
      of admission. CONCLUSIONS: In patients with acute hematogenous osteomyelitis, CRP
      increased and especially decreased significantly faster than ESR, reflecting the
      effectiveness of the therapy given and predicting recovery more sensitively than
      ESR or WBC count.

PMID- 8265326
TI  - The "88% saturation test": a simple lung function test for young children.
AB  - OBJECTIVE: The 88% saturation test (88%-SAT) was developed as an alternative to
      standard spirometry for those young children unable to perform standard forced
      expiratory maneuvers. In adults, this test revealed rapid desaturation in those
      persons with a history of asthma when compared with healthy control subjects.
      Similar findings in children were tested. SETTING: Tertiary care hospital.
      PATIENTS: Thirty-three former premature infants (28.3 +/- 2.3 weeks gestation),
      aged 5 to 7 years, who were participating in a follow-up study, were enrolled in
      this study. DESIGN: The study compared the 88%-SAT with standard spirometry and
      respiratory health characteristics ascertained through a parental questionnaire.
      The 88%-SAT consists of continuous measurement of hemoglobin saturation by pulse
      oximetry (SaO2) while the subject breathes a nonhumidified 12% oxygen and
      nitrogen mixture for 10 minutes or until SaO2 decreases to 88%, whichever occurs
      first. Abnormal 88%-SAT was defined as a decrease of SaO2 to 88% within the 10
      minute period, and abnormal spirometry was defined using standardized values.
      RESULTS: Of the 20 children who successfully completed both spirometry and the
      88%-SAT, 10 had normal spirometry results and did not desaturate to 88%, and 5
      had abnormal spirometry and 88%-SAT results. Four children did not desaturate
      during the 88%-SAT, but had abnormal spirometry results, and one child had
      abnormal 88%-SAT results, but normal spirometry. Ten additional children
      completed the 88%-SAT, but not standard spirometry. Three children were unable to
      complete either test. Of those 30 children tested, 7 (23%) had a history of
      reactive airways disease, and all 7 had abnormal 88%-SAT results. The 88%-SAT had
      greater sensitivity (100% vs 75%) and specificity (87% vs 63%) than spirometry in
      identifying children with known reactive airways disease. The mean McCarthy
      general cognitive index (GCI) of the group performing both spirometry and the 88%
      SAT (n = 20) achieved a mean (+/- SD) GCI of 96.2 +/- 16.7, and the group (n =
      30) that completed the 88%-SAT had a mean (+/- SD) GCI of 75.2 +/- 26.3 (chi 2 P
      < .012). The 10 children able to perform only the 88%-SAT had a mean GCI (+/- SD)
      of 72.8 +/- 26.9, and the 3 children unable to perform either test had a mean GCI
      (+/- SD) of 63 +/- 11. CONCLUSIONS: Our data suggest that the 88%-SAT may be more
      effective than spirometry for identifying reactive airways disease in young,
      uncooperative, or developmentally delayed children. The dry air of the hypoxic
      inspired gas may function as an airway challenge, leading to decreased
      oxygenation in patients with reactive airways.

PMID- 8265327
TI  - The role of aversive bittering agents in the prevention of pediatric poisonings.

PMID- 8265328
TI  - An evaluation of autonomic nervous system function in patients with Prader-Willi
      syndrome.
AB  - OBJECTIVE: Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder
      in which many cardinal features may have a neurologically based pathophysiology
      involving both the central and peripheral components of the autonomic nervous
      system. Autonomic nervous system function was studied noninvasively in a group of
      subjects with PWS and control subjects to determine whether autonomic nervous
      system dysfunction exists as part of the PWS. DESIGN/SETTING: This cross
      sectional study was performed in the neurophysiology laboratory at a tertiary
      care facility. METHODS: Evaluation included anthropometric measurements and
      calculation of a body mass index (BMI). Simultaneous electrocardiography and
      serial recordings of pulse rate and systolic/diastolic mean arterial blood
      pressures during orthostatic maneuvers were taken. Pupillary response to the
      instillation of dilute pilocarpine and measurements of plasma norepinephrine at
      rest and after standing were also obtained. Results were analyzed using two
      tailed t tests, Fisher exact test, analysis of variance, and analysis of
      covariance adjusting for age, gender, and BMI. PATIENTS: There were 14 subjects
      with PWS (8 female, 6 male; aged 4 to 40 years, mean age 16 years) and 8 control
      subjects (4 female, 4 male; aged 5 to 37 years, mean age 19 years). RESULTS:
      Abnormal findings were obtained only in subjects with PWS. Analysis of covariance
      adjusting for age, gender, and BMI revealed a trend for subjects with PWS to have
      lower resting diastolic blood pressure (P < .09) and significantly less change in
      diastolic blood pressure after standing (P < .02). Subjects with PWS had
      significantly greater BMI than did control subjects (P < .001), which correlated
      significantly with all pulse rate measurements where the greater the BMI the
      higher the pulse rate at rest (r = .25, P < .04) and the lower the pulse rate
      after arising from lying to standing at both 15 and 30 seconds (r = .17, P < .1;
      r = .55, P < .08 respectively). Pupillary constriction of 2 mm or more was seen
      in 7 of 14 subjects with PWS and in no control subjects (P < .004). The 30:15 R-R
      interval ratio was abnormal in 6 of 14 subjects with PWS and in no control
      subjects (P < .03). CONCLUSIONS: These results suggest that patients with PWS
      have a detectable underlying autonomic dysfunction characterized principally by
      diminished parasympathetic nervous system activity.

PMID- 8265329
TI  - Does prenatal and infancy nurse home visitation have enduring effects on
      qualities of parental caregiving and child health at 25 to 50 months of life?
AB  - OBJECTIVE: To examine, during the 3rd and 4th years of life, the health,
      development, rates of child maltreatment, and living conditions of children who
      had been enrolled in a randomized trial of nurse home visitation during pregnancy
      and first 2 years of their lives. DESIGN: Prospective follow-up of families who
      had been randomly assigned to nurse-visited and comparison conditions. SETTING:
      Study conducted in semirural community in upstate New York. Families dispersed
      among 14 other states during 2-year period after children's second birthdays.
      PARTICIPANTS: Four hundred women were recruited through a health department
      antepartum clinic and offices of private obstetricians and were registered before
      30th week of pregnancy. All women had no previous live births and 85% were either
      teenaged (< 18 years at registration), unmarried, or from Hollingshead social
      classes IV or V. Analysis focused on whites, who comprised 89% of sample.
      INTERVENTION: Nurse home visitation from pregnancy through second year of the
      child's life. MAIN RESULTS: There were no treatment differences in the rates of
      child abuse and neglect or children's intellectual functioning from 25 to 48
      months of age. Nurse-visited children, nevertheless, lived in homes with fewer
      hazards for children; they had 40% fewer injuries and ingestions and 45% fewer
      behavioral and parental coping problems noted in the physician record; and they
      made 35% fewer visits to the emergency department than did children in the
      comparison group. Nurse-visited mothers were observed to be more involved with
      and to punish their children to a greater extent than were mothers in the
      comparison group. The functional meaning of punishment differed between the nurse
      visited and comparison families. CONCLUSIONS: The program does have enduring
      effects on certain aspects of parental caregiving, safety of the home, and
      children's use of the health care system, but it may be necessary to extend the
      length of the program for families at highest risk to produce lasting reductions
      in child abuse and neglect.

PMID- 8265330
TI  - Nursing: what's in a name? Plenty!

PMID- 8265331
TI  - Ancient genomes, wise bodies, unhealthy people: limits of a genetic paradigm in
      biology and medicine.

PMID- 8265332
TI  - Fever: a possible strategy for membrane homeostasis during infection.

PMID- 8265333
TI  - Priorities in the application of genetic principles to the human condition: a
      dissident view.

PMID- 8265334
TI  - The thymus, suffocation, and sudden infant death syndrome--social agenda or
      hubris?

PMID- 8265335
TI  - France and the early history of organ transplantation.

PMID- 8265336
TI  - The impact of surgery on fine art.

PMID- 8265337
TI  - Degenerate heredity: the history of a doctrine in medicine and biology.

PMID- 8265338
TI  - Dynamic revelations in scientific research.

PMID- 8265339
TI  - The P1 family: a new class of nuclear mammalian proteins related to the yeast Mcm
      replication proteins.
AB  - Monospecific antibodies against an oligopeptide, conserved among the Mcm class of
      yeast replication proteins, were used to screen a human cDNA library. Eight of
      the isolated cDNA clones have the potential to code for sections of proteins with
      high sequence similarities to the yeast proteins Mcm3 and Cdc46 from
      Saccharomyces cerevisiae and Cdc21 from S. pombe. Our results establish a novel
      and highly conserved family of nuclear proteins in mammalian cells.

PMID- 8265340
TI  - Synonymous codon usage in Zea mays L. nuclear genes is varied by levels of C and
      G-ending codons.
AB  - A multivariate statistical method called correspondence analysis was used to
      examine the codon usage of one-hundred-and-one nuclear genes of maize (Zea mays
      L.). Forty percent of the variation in codon usage was due to bias toward G or C
      ending versus A or U-ending codons. Differences in levels of G-ending codons
      showed the weakest correlation with the major codon usage bias. The bias toward C
      or U versus A or G in the silent third nucleotide position of synonymous codons
      accounted for approximately 10% of the variation in codon usage. The G+C content
      of the silent third nucleotide position of coding regions was not strongly
      correlated with G+C content of introns. Codon usage was strongly biased toward
      codons ending in G or C for a number of highly expressed genes including most
      light-regulated chloroplast proteins, ABA-induced proteins, histones, and
      anthocyanin biosynthetic enzymes. Codon usage of genes encoding storage proteins
      and regulatory proteins, such as transposases, kinases, phosphatases and
      transcription factors, was more random than that of genes encoding cytosolic
      enzymes with similar bias toward G or C-ending codons. Codon usage in maize may
      reflect both regional bias on nucleotide composition and selection on the silent
      third nucleotide position.

PMID- 8265341
TI  - Yeast open reading frame YCR14C encodes a DNA beta-polymerase-like enzyme.
AB  - We have shown by activity gel that overexpression in E. coli of a yeast
      chromosome 3 open reading frame (ORF) designated YCR14C and bearing homology to
      mammalian DNA polymerases beta results in a new DNA polymerase in the host cells.
      The molecular mass of this enzyme corresponded to the YCR14C-predicted 67 kDa
      protein, and NH2-terminal amino acid sequencing confirmed that the expressed
      protein was encoded by the yeast ORF. This new yeast DNA polymerase was purified
      to homogeneity from E.coli. In a fashion similar to that of mammalian beta
      polymerases, the purified yeast enzyme exhibited distributive DNA synthesis on
      DNA substrate with a single-stranded template and processive gap-filling
      synthesis on a short-gapped DNA substrate. Activity of this yeast beta-polymerase
      like enzyme was sensitive to the beta-polymerase inhibitor ddNTP and resistant to
      both 1 mM NEM and neutralizing antibody to E. coli DNA polymerase I. These
      results, therefore, indicate that YCR14C encodes a DNA beta-polymerase-like
      enzyme in yeast, and we name it DNA polymerase IV. Yeast strains harboring a
      deletion mutation of the pol IV gene are viable, they exhibit no increase in
      sensitivity to ultraviolet light, ionizing radiation or alkylating agents, and
      sporulation and spore viability are not affected in the mutant.

PMID- 8265342
TI  - Single point mutations in domain II of the yeast mitochondrial release factor mRF
      1 affect ribosome binding.
AB  - We have recently described two yeast strains that are mutated in the MRF1 gene
      encoding the mitochondrial release factor mRF-1. Both mutants provoke gene
      specific defects in mitochondrial translational termination. In the present study
      we report the cloning, sequencing, as well as an analysis of residual activities
      of both mutant mrf1 alleles. Each allele specifies a different single amino acid
      substitution located one amino acid apart. The amino acid changes do not affect
      the level or cellular localization of the mutant proteins, since equal amounts of
      wild type and mutant mRF-1 were detected in the mitochondrial compartment. Over
      expression of the mutant alleles in wild type and mrf1 mutant yeast strains
      produces a phenotype consistent with a reduced affinity of the mutant release
      factors for the ribosome, indicating that the mutations map in a release factor
      domain involved in ribosome binding. We also demonstrate that nonsense
      suppression caused by a mutation in the mitochondrial homolog of the E. coli
      small ribosomal protein S4 can be reversed by a slight over-expression of the
      MRF1 gene.

PMID- 8265343
TI  - Translational repression by the human iron-regulatory factor (IRF) in
      Saccharomyces cerevisiae.
AB  - The regulation of the synthesis of ferritin and erythroid 5-aminolevulinate
      synthase in mammalian cells is mediated by the interaction of the iron regulatory
      factor (IRF) with a specific recognition site, the iron responsive element (IRE),
      in the 5' untranslated regions (UTRs) of the respective mRNAs. A new modular
      expression system was designed to allow reconstruction of this regulatory system
      in Saccharomyces cerevisiae. This comprised two components: a constitutively
      expressed reporter gene (luc; encoding luciferase) preceded by a 5' UTR including
      an IRE sequence, and an inducibly expressed cDNA encoding human IRF. Induction of
      the latter led to the in vivo synthesis of IRF, which in turn showed IRE-binding
      activity and also repressed translation of the luc mRNA bearing an IRE-containing
      5' UTR. The upper stem-loop region of an IRE, with no further IRE-specific
      flanking sequences, sufficed for recognition and repression by IRF. Translational
      regulation of IRE-bearing mRNAs could also be demonstrated in cell-free yeast
      extracts. This work defines a minimal system for IRF/IRE translational regulation
      in yeast that requires no additional mammalian-specific components, thus
      providing direct proof that IRF functions as a translational repressor in vivo.
      It should be a useful tool as the basis for more detailed studies of eukaryotic
      translational regulation.

PMID- 8265344
TI  - Enzymic removal of 5-methylcytosine from DNA by a human DNA-glycosylase.
AB  - DNA 5-methylcytosine is a major factor in the silencing of mammalian genes; it is
      involved in gene expression, differentiation, embryogenesis and neoplastic
      transformation. A decrease in DNA 5-methylcytosine content is associated with
      activation of specific genes. There is much evidence indicating this to be an
      enzymic process, with replacement of 5-methylcytosine by cytosine. We demonstrate
      here enzymic release of 5-methylcytosines from DNA by a human 5-methylcytosine
      DNA glycosylase activity, which affords a possible mechanism for such
      replacement. This activity generates promutagenic apyrimidinic sites, which can
      be related to the high frequency of mutations found at DNA 5-methylcytosine loci.
      The recovery of most released pyrimidines as thymines indicates subsequent
      deamination of free 5-methylcytosines by a 5-methylcytosine deaminase activity.
      This prevents possible recycling of 5-methylcytosine into replicative DNA
      synthesis via a possible 5-methyl-dCTP intermediate synthesized through the
      pyrimidine salvage pathway. Taken together, these findings indicate mechanisms
      for removal of 5-methylcytosines from DNA, hypermutability of DNA 5
      methylcytosine sites, and exclusion of 5-methylcytosines from DNA during
      replication.

PMID- 8265345
TI  - Single base pair mutation analysis by PNA directed PCR clamping.
AB  - A novel method that allows direct analysis of single base mutation by the
      polymerase chain reaction (PCR) is described. The method utilizes the finding
      that PNAs (peptide nucleic acids) recognize and bind to their complementary
      nucleic acid sequences with higher thermal stability and specificity than the
      corresponding deoxyribooligonucleotides and that they cannot function as primers
      for DNA polymerases. We show that a PNA/DNA complex can effectively block the
      formation of a PCR product when the PNA is targeted against one of the PCR primer
      sites. Furthermore, we demonstrate that this blockage allows selective
      amplification/suppression of target sequences that differ by only one base pair.
      Finally we show that PNAs can be designed in such a way that blockage can be
      accomplished when the PNA target sequence is located between the PCR primers.

PMID- 8265346
TI  - Dipentafluorophenyl carbonate--a reagent for the synthesis of oligonucleotides
      and their conjugates.
AB  - Dipentafluorophenyl carbonate has been successfully used as condensing agent for
      the internucleotide bond formation in the synthesis of oligonucleotides via H
      phosphonate approach. The mechanism of a nucleotide component activation with
      this reagent has been investigated with the help of 31P NMR spectroscopy. It was
      shown that preactivation of deoxynucleoside H-phosphonate with
      dipentafluorophenyl carbonate has no influence on the efficiency of the
      synthesis. This reagent is highly reactive, nonhygroscopic and stable on storage
      at room temperature. The effectiveness of dipentafluorophenyl carbonate in the
      oligonucleotide chemistry has been demonstrated in the solid-phase synthesis of
      10-50-mers on 0.2, 1 and 10 mumol scales. The use of this reagent for the
      derivatisation of polymer supports as well as for the synthesis of
      oligonucleotide conjugates with polyethylene glycol and a lipid is described.

PMID- 8265347
TI  - Structure of the gene encoding the 14.5 kDa subunit of human RNA polymerase II.
AB  - The structure of the gene encoding the 14.5 kDa subunit of the human RNA
      polymerase II (or B) has been elucidated. The gene consists of six exons, ranging
      from 52 to over 101 bp, interspaced with five introns ranging from 84 to 246 bp.
      It is transcribed into three major RNA species, present at low abundance in
      exponentially growing HeLa cells. The corresponding messenger RNAs contain the
      same open reading frame encoding a 125 amino acid residue protein, with a
      calculated molecular weight of 14,523 Da. This protein (named hRPB14.5) shares
      strong homologies with the homologous polymerase subunits encoded by the
      Drosophila (RpII15) and yeast (RPB9) genes. Cysteines characteristic of two zinc
      fingers are conserved in all three corresponding sequences and, like the yeast
      protein, the hRPB14.5 subunit exhibits zinc-binding activity.

PMID- 8265348
TI  - Identification of positive and negative regulatory elements involved in the
      retinoic acid/cAMP induction of Fgf-3 transcription in F9 cells.
AB  - The proto-oncogene Fgf-3 has been implicated as an important signalling molecule
      in vertebrate development. In the mouse, it is expressed for a limited time at a
      multitude of sites from embryonic day 7 to birth. Transcription of Fgf-3
      initiates at three promoter regions resulting in the generation of various mRNAs
      which nevertheless all encode the same protein products. A 1.7kb DNA fragment
      which encompasses these regions was joined to the CAT reporter gene and shown to
      function as a promoter in embryonal carcinoma cells. In stable transfectants the
      promoter retains its retinoic acid inducibility, initiating transcription at the
      same cap-sites as the endogenous gene. In differentiated F9 cells, transient
      transfection of progressive and targeted deletion mutants of the promoter region
      has revealed at least two positive and three negative regulatory elements. With
      one exception, loss of these elements was shown to dramatically affect promoter
      activity in stable transfectants of F9 cells. However the promoter remained
      inducible by retinoic acid to differing degrees, apart from deletions
      encompassing PS-4A which essentially abolished promoter activity in both
      undifferentiated and differentiated cells. The sequences of these potential
      regulatory regions were further defined using DNase-I footprinting, revealing
      some similarities to consensus binding sites for known transcription factors.

PMID- 8265349
TI  - Modified binding of proteins from calcitonin-negative tumor cells to the
      neuroendocrine-specific CANNTG motif of the calcitonin gene.
AB  - Transcription of the calcitonin (CT) gene in the medullary thyroid carcinoma
      (MTC) cell line TT is modulated by a neuroendocrine-specific enhancer fragment
      (nucleotides -965 to -905) containing two CANNTG motifs (E2 and E3) and an ETs
      like response element. To determine the cell-specific component of this fragment,
      oligonucleotides containing the individual elements were inserted in front of a
      minimal CT promoter and tested for reporter protein production in CT-positive
      (TT) and -negative (RO-D81 and HeLa) cells. In TT cells, using two copies of E2
      or four copies of Ets increased minimal promoter activity a 20-40 fold. Using two
      copies of E3 had no effect on minimal promoter activity. In CT-negative MTC cells
      (RO-D81), the Ets response element was active but the two copies of E2 were not.
      Similar results were obtained with the non-neuroendocrine cell-line HeLa. I
      therefore concluded that E2 was the cell-type-specific component of the enhancer.
      An E2-specific binding protein was detected in both MTC cell lines but not in
      HeLa. This protein had different mobility and DNA-binding specificity in CT
      positive TT cells and CT-negative RO-D81 cells. In conclusion, the CAGCTG motif
      of E2 modulated the cell-specific transcription of the CT gene, and its
      inactivation in CT-negative MTC cells correlated with modifications in its
      binding proteins.

PMID- 8265350
TI  - Telomere processing in Euplotes.
AB  - In Euplotes crassus millions of telomeres are synthesized during the sexual phase
      of the life cycle. Since these newly synthesized telomeres are longer than normal
      macronuclear telomeres, they must be trimmed to the mature size. We have examined
      the timing and mechanism of this trimming step. We have shown that a sudden
      decrease in telomere length takes place at a specific time during macronuclear
      development. The decrease in telomere length is not caused by incomplete
      replication of the most terminal DNA sequences; rather it is the result of an
      active processing event that occurs independently of DNA replication. The
      developmentally regulated telomere shortening that takes place in Euplotes is
      reminiscent of the sudden reductions in telomere length which have been observed
      in other eukaryotes.

PMID- 8265351
TI  - Distinct DNA binding preferences for the c-Myc/Max and Max/Max dimers.
AB  - The transcription factor c-Myc and its dimerisation partner Max are members of
      the basic/helix-loop-helix/leucine-zipper (bHLH-Z) family and bind to the DNA
      core sequence CACGTG. Using a site-selection protocol, we determined the complete
      12 base pair consensus binding sites of c-Myc/Max (RACCACGTGGTY) and Max/Max
      (RANCACGTGNTY) dimers. We find that the c-Myc/Max dimer fails to bind the core
      when it is flanked by a 5'T or a 3'A, while the Max/Max dimer readily binds such
      sequences. Furthermore we show that inappropriate flanking sequences preclude
      transactivation by c-Myc in vivo. In conclusion, Max/Max dimers are less
      discriminatory than c-Myc/Max and may regulate other genes in addition to c
      Myc/Max targets.

PMID- 8265352
TI  - Isolation of U3 snoRNP from CHO cells: a novel 55 kDa protein binds to the
      central part of U3 snoRNA.
AB  - U3 snoRNP, the most abundant of the small nucleolar ribonucleoprotein particles
      (snoRNPs), has previously been demonstrated to participate in pre-rRNA
      maturation. Here we report the purification of U3 snoRNP from CHO cells using
      anti-m3G-immunoaffinity and mono Q anion-exchange chromatography. Isolated U3
      snoRNPs contain three novel proteins, of 15, 50 and 55 kDa respectively. These
      proteins may represent core U3 snoRNP proteins whose binding mediates the
      association of other proteins, such as fibrillarin, that are lost during
      purification. Using a rabbit antiserum raised against the 55 kDa protein, and an
      in vitro reconstitution assay, we have localised the 55 kDa protein binding site
      on the U3 snoRNA. Stable binding of the 55 kDa protein requires sequences located
      between nucleotides 97 and 204 of the human U3 snoRNA, including the
      evolutionarily conserved B and C sequence motifs.

PMID- 8265353
TI  - Identification and functional analysis of a novel yeast small nucleolar RNA.
AB  - snR31 is a RNA species of 225 nt. which has the trimethyl guanosine cap structure
      typical of small nuclear RNAs (snRNAs) and yeast small nucleolar RNAs (snoRNAs),
      and is associated with the nucleolar proteins fibrillarin (NOP1) and GAR1. On sub
      nuclear fractionation, snR31 behaves like other snoRNAs, and is enriched in a
      nucleolar fraction. The SNR31 genomic locus is close to the SNR5 locus, which
      encodes another snoRNA. The two genes are divergently transcribed with 217 bp
      separating the transcription start sites. Disruption of the SNR31 gene does not
      detectably impair growth in a haploid strain. Analyses of pre-rRNA processing in
      wild-type and snr31- strains shows some accumulation of the 35S primary
      transcript in the mutant, indicating a mild impairment of the initial steps in
      pre-rRNA processing.

PMID- 8265354
TI  - SnR31, snR32, and snR33: three novel, non-essential snRNAs from Saccharomyces
      cerevisiae.
AB  - Genes for three novel yeast snRNAs have been identified and tested for
      essentiality. Partial sequence information was developed for RNA extracted from
      isolated nuclei and the respective gene sequences were discovered by screening a
      DNA sequence database. The three RNAs contain 222, 188 and 183 nucleotides and
      are designated snR31, snR32 and snR33, respectively. Each RNA is derived from a
      single copy gene. The SNR31 gene is adjacent to a gene for an unnamed protein
      associated with the cap-binding protein eIF-4E. The SNR32 gene is next to a gene
      for ribosomal protein L41 and the gene for SNR33 is on chromosome III, between
      two open reading frames with no known function. Genetic disruption analyses
      showed that none of the three snRNAs is required for growth. The new RNAs bring
      the number of non-spliceosomal snRNAs characterized thus far in S. cerevisiae to
      14, of which only three are essential.

PMID- 8265355
TI  - Separation of mutant and wild-type ribosomes based on differences in their anti
      Shine-Dalgarno sequence.
AB  - We describe a system to isolate 30S ribosomal subunits which contain targeted
      mutations in their 16S rRNA. The mutations of interest should be present in so
      called specialized 30S subunits which have an anti-Shine-Dalgarno sequence that
      is altered from 5' ACCUCC to 5' ACACAC. These plasmid-encoded specialized 30S
      subunits are separated from their chromosomally encoded wild-type counterparts by
      affinity chromatography that exploits the different Shine-Dalgarno
      complementarity. An oligonucleotide complementary to the 3' end of wild-type 16S
      rRNA and attached to a solid phase matrix retains the wild-type 30S subunits. The
      flow-through of the column contains close to 100% mutant 30S subunits.
      Toeprinting assays demonstrate that affinity column treatment does not cause
      significant loss of activity of the specialized particles in initiation complex
      formation, whereas elongation capacity as determined by poly(Phe) synthesis is
      only slightly decreased. The method described offers an advantage over total
      reconstitution from in vitro transcribed mutant 16S rRNA since our 30S subunits
      contain the naturally occurring base modifications in their 16S rRNA.

PMID- 8265356
TI  - Oligonucleotide circularization by template-directed chemical ligation.
AB  - An efficient method for producing the covalent closure of oligonucleotides on
      complementary templates by the action of BrCN was developed. A rational design of
      linear precursor oligonucleotides was studied, and the effect of factors such as
      oligonucleotide concentration and oligomer-template length ratio was evaluated.
      The efficiency of circularization was shown to correlate well with the secondary
      structure of the precursor oligomer (as predicted by a simple computer analysis),
      hairpin-like structures bearing free termini clearly favouring the
      circularization reaction. A novel idea, consisting of the incorporation of non
      nucleotide insertions in the precursor oligomer (namely, 1,2-dideoxy-D
      ribofuranose residues), may render this method universal and highly effective. An
      original set of assays was developed to confirm the circular structure of the
      covalently closed oligonucleotides.

PMID- 8265357
TI  - Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2
      to 92.8 minutes.
AB  - We present the sequence of 176 kilobases of the Escherichia coli K-12 genome,
      from katG at 89.2 to an open reading frame (ORF) of unknown function at 92.8
      minutes on the genetic map. This brings the total of contiguous sequence from the
      E. coli genome project to 500 kb (81.5 to 92.8 minutes). This segment contains
      134 putative coding genes (ORFs) of which 66 genes were previously identified.
      Eight new genes--acs, pepE, and nrfB-G--were identified as well as the previously
      mapped gldA and alr genes. Still, 58 ORFs remain unidentified despite literature
      and similarity searches. The arrangement of proposed genes relative to possible
      promoters and terminators suggests 55 potential transcription units. Other
      features include 13 REP elements, one IRU (ERIC) repeat, 59 computer-predicted
      bends, 42 Chi sites and one new grey hole. Sixteen signal peptides were found,
      including those of lamB, btuB, and malE. Two ribosomal RNA loci, rrnB and rrnE,
      are located in this segment, so we have now sequenced four of the seven E. coli
      rRNA loci. Comparison of the rRNA loci reveals some differences in the ribosomal
      structural RNAs which are generally compatible with the proposed secondary
      structures.

PMID- 8265358
TI  - NMR studies of G:A mismatches in oligodeoxyribonucleotide duplexes modelled after
      ribozymes.
AB  - The structures of two oligodeoxyribonucleotide duplexes, the base sequences of
      which were modelled after both a hammerhead ribozyme and a small metalloribozyme,
      were studied by NMR. Both duplexes contain adjacent G:A mismatches; one has a
      PyGAPu:PyGAPu sequence and the other a PyGAPy:PuGAPu sequence. It is concluded on
      the basis of many characteristic NOEs that in both duplexes G:A base pairs are
      formed in the unique 'sheared' form, where an amino proton instead of an imino
      proton of G is involved in the hydrogen bonding, and G and A bases are arranged
      'side by side' instead of 'head to head'. A photo-CIDNP experiment, which gives
      unique and independent information on the solvent accessibility of nucleotide
      bases, also supports G:A base pairing rather than a bulged-out structure of G and
      A residues. This is the first demonstration that not only the PyGAPu:PyGAPu
      sequence but also the PyGAPy:PuGAPu sequence can form the unique sheared G:A base
      pairs. Taking the previous studies on G:A mismatches into account, the idea is
      suggested that a PyGA:GAPu sequence is a minimum and essential element for the
      formation of the sheared G:A base pairs. The sheared G:A base pairs in the
      PyGAPu:PyGAPu sequence are suggested to be more stable than those in the
      PyGAPy:PuGAPu sequence. This is explained rationally by the idea proposed above.

PMID- 8265359
TI  - DNA ligase III is the major high molecular weight DNA joining activity in SV40
      transformed human fibroblasts: normal levels of DNA ligase III activity in Bloom
      syndrome cells.
AB  - The phenotypes of cultured cell lines established from individuals with Bloom
      syndrome (BLM), including an elevated spontaneous frequency of sister chromatid
      exchanges (SCEs), are consistent with a defect in DNA joining. We have
      investigated the levels of DNA ligase I and DNA ligase III in an SV40-transformed
      control and BLM fibroblast cell line, as well as clonal derivatives of the BLM
      cell line complemented or not for the elevated SCE phenotype. No differences in
      either DNA ligase I or DNA ligase III were detected in extracts from these cell
      lines. Furthermore, the data indicate that in dividing cultures of SV40
      transformed fibroblasts, DNA ligase III contributes > 85% of high molecular
      weight DNA joining activity. This observation contrasts with previous studies in
      which DNA ligase I was reported to be the major DNA joining activity in extracts
      from proliferating mammalian cells.

PMID- 8265360
TI  - Cloning and expression of the hypoxanthine-guanine phosphoribosyltransferase gene
      from Trypanosoma brucei.
AB  - The hypoxanthine-guanine phosphoribosyltransferase (HGPRT) enzyme of Trypanosoma
      brucei and related parasites provides a rational target for the treatment of
      African sleeping sickness and several other parasitic diseases. To characterize
      the T. brucei HGPRT enzyme in detail, the T. brucei hgprt was isolated within a
      4.2 kb SalI-KpnI genomic insert and sequenced. Nucleotide sequence analysis
      revealed an open reading frame of 630 bp that encoded a protein of 210 amino
      acids with a M(r) = 23.4 kd. After gap alignment, the T. brucei HGPRT exhibited
      21-23% amino acid sequence identity, mostly in three clustered regions, with the
      HGPRTs from human, S. mansoni, and P falciparum, indicating that the trypanosome
      enzyme was the most divergent of the group. Surprisingly, the T. brucei HGPRT was
      more homologous to the hypoxanthine phosphoribosyltransferase (HPRT) from the
      prokaryote V. harveyi than to the eukaryotic HGPRTs. Northern blot analysis
      revealed two trypanosome transcripts of 1.4 and 1.9 kb, each expressed to
      equivalent degrees in insect vector and mammalian forms of the parasite. The T.
      brucei hgprt was inserted into an expression plasmid and transformed into S phi
      606 E. coli that are deficient in both HPRT and xanthine-guanine
      phosphoribosyltransferase activities. Soluble, enzymatically active recombinant
      T. brucei HGPRT was expressed to high levels and purified to homogeneity by GTP
      agarose affinity chromatography. The purified recombinant enzyme recognized
      hypoxanthine, guanine, and allopurinol, but not xanthine or adenine, as
      substrates and was inhibited by a variety of nucleotide effectors. The
      availability of a molecular clone encoding the T. brucei hgprt and large
      quantities of homogeneous recombinant HGPRT enzyme provides an experimentally
      manipulable molecular and biochemical system for the rational design of novel
      therapeutic agents for the treatment of African sleeping sickness and other
      diseases of parasitic origin.

PMID- 8265361
TI  - Re-engineering the polymerase domain of Klenow fragment and evaluation of
      overproduction and purification strategies.
AB  - We describe experiments to produce large quantities of the polymerase domain of
      E. coli DNA polymerase I for biochemical and biophysical studies. The polymerase
      domain derivative used in previous studies was insoluble when overproduced and
      tended to aggregate during purification. These problems were solved by a
      combination of two distinct strategies. By changing the expression system, we
      were able to obtain the overproduced protein in a soluble form, a necessary first
      step since attempts to purify the polymerase domain from the insoluble pellet
      were unsuccessful. The tendency of the polymerase domain to aggregate was
      eliminated by re-engineering the protein so as to remove both a solvent-exposed
      hydrophobic patch and a potentially unstructured region at the extreme N
      terminus. Unlike the original construct, the re-engineered derivatives
      chromatographed as a single species and could be purified to homogeneity in good
      yield. Our experience in this study emphasizes the level of ignorance of the
      factors that influence protein overproduction and the need, in difficult cases,
      to evaluate many strategies in a semi-empirical manner.

PMID- 8265362
TI  - The stereochemical course of the first step of pre-mRNA splicing.
AB  - We have determined the effects on splicing of sulfur substitution of the non
      bridging oxygens in the phosphodiester bond at the 5' splice site of a pre-mRNA
      intron. Pre-mRNAs containing stereochemically pure Rp and Sp phosphorothioate
      isomers were produced by ligation of a chemically synthesized modified RNA
      oligonucleotide to enzymatically synthesized RAs. When these modified pre-mRNA
      substrates were tested for in vitro splicing activity in a HeLa cell nuclear
      extract system, the RNA with the Rp diastereomeric phosphorothioate was not
      spliced while the Sp diastereomeric RNA spliced readily. The sulfur-containing
      branched trinucleotide was purified from the splicing reaction of the Sp RNA and
      analyzed by cleavage with a stereospecific nuclease. The results showed that the
      Sp phosphorothioate was inverted during the splicing reaction to the Rp
      configuration; a finding previously obtained for a Group I self-splicing RNA.
      This inversion of configuration is consistent with a transesterification
      mechanism for pre-mRNA splicing. The lack of splicing of the Rp modified RNA also
      suggests that the pro-Rp oxygen at the 5' splice site is involved in a critical
      chemical contact in the splicing mechanism. Additionally, we have found that the
      HeLa cell RNA debranching enzyme is inactive on branches containing an Rp
      phosphorothioate.

PMID- 8265363
TI  - Human nicotinic acetylcholine receptor alpha-subunit isoforms: origins and
      expression.
AB  - A majority of the autoantibodies in the disease myasthenia gravis (MG) are
      directed against the alpha-subunit of the muscle nicotinic acetylcholine receptor
      (AChR). Unlike AChR alpha-subunits previously characterised from other species,
      the human alpha-subunit exists as two isoforms. The isoforms are generated by
      alternate splicing of an additional exon located between exons P3 and P4, termed
      P3A. The 25 amino acids encoded by the P3A exon are incorporated into the
      extracellular region of the alpha-subunit, and so may be relevant to the
      pathogenesis of MG. Genomic sequences from rhesus monkey, and from dog and cat,
      which are susceptible to MG, were characterised between AChR alpha-subunit exons
      P3 and P4. Although regions homologous to the P3A exon were identified for each
      of these species, analysis by RT-PCR showed that they are not expressed. At
      variance with a previous report, constitutive expression of mRNA encoding the
      human P3A+ alpha-subunit isoform was not detected in heart, kidney, liver, lung
      or brain. Differential expression of the two alpha-subunit isoforms was not seen
      during fetal muscle development or in muscle from MG patients. In all cases where
      mRNAs encoding the two alpha-subunit isoforms have been detected, they are
      present at an approximate 1:1 ratio.

PMID- 8265364
TI  - Variant mitochondrial plasmids of broad bean arose by recombination and are
      controlled by the nuclear genome.
AB  - Various cytoplasms of broad bean contain three mitochondrial plasmids (mtp1, 2
      and 3), previously described. In cytoplasm 350 we have observed several
      additional mitochondrial plasmids, varying in number and in identity according to
      the nuclear background. Replacement of the nucleus by backcrossing led to the
      appearance or disappearance of additional plasmids, indicating that the nuclear
      genome controls either the creation or the copy level of mitochondrial plasmids.
      Analysis of eight variant additional plasmids (mtp4-11) suggests that they all
      result from a double recombination event between mtp1 and mtp2. In all cases, one
      recombination point was located within a 276-bp sequence, identical in both
      plasmids. For 7 plasmids, the region in which the second recombination event
      occurred could be narrowed down to a short stretch containing imperfect tandem
      repeats of a 31-bp motif. The largest sequence shared by the recombination
      regions was hexanucleotide GCGACG.

PMID- 8265365
TI  - The migration behaviour of DNA replicative intermediates containing an internal
      bubble analyzed by two-dimensional agarose gel electrophoresis.
AB  - Initiation of DNA replication in higher eukaryotes is still a matter of
      controversy. Some evidence suggests it occurs at specific sites. Data obtained
      using two-dimensional (2D) agarose gel electrophoresis, however, led to the
      notion that it may occur at random in broad zones. This hypothesis is primarily
      based on the observation that several contiguous DNA fragments generate a mixture
      of the so-called 'bubble' and 'simple Y' patterns in Neutral/neutral 2D gels. The
      interpretation that this mixture of hybridisation patterns is indicative for
      random initiation of DNA synthesis relies on the assumption that replicative
      intermediates (RIs) containing an internal bubble where initiation occurred at
      different relative positions, generate comigrating signals. The latter, however,
      is still to be proven. We investigated this problem by analysing together, in the
      same 2D gel, populations of pBR322 RIs that were digested with different
      restriction endonucleases that cut the monomer only once at different locations.
      DNA synthesis begins at a specific site in pBR322 and progresses in a uni
      directional manner. Thus, the main difference between these sets of RIs was the
      relative position of the origin. The results obtained clearly showed that
      populations of RIs containing an internal bubble where initiation occurred at
      different relative positions do not generate signals that co-migrate all-the-way
      in 2D gels. Despite this observation, however, our results support the notion
      that random initiation is indeed responsible for the peculiar 'bubble' signal
      observed in the case of several metazoan eukaryotes.

PMID- 8265366
TI  - Polyamine-linked oligonucleotides for DNA triple helix formation.
AB  - The concept of antigene therapy of disease is based on the ability of an
      oligonucleotide (the therapeutic agent) to bind to double-stranded genomic DNA
      (the target associated with the disease). Examples are herein given of the
      linkage of a series of polyamines to a 21-mer homopyrimidine oligonucleotide.
      These conjugated 21-mers can each form a triple helix with an appropriate double
      stranded homopurine-homopyrimidine DNA according to Hoogsteen base-pairing rules.
      No triple helix was found when unmodified third strand was used at 10 mM sodium
      phosphate, pH 6.5, 100 mM sodium chloride solution. In contrast, the spermine
      conjugated oligonucleotide had a melting temperature of 42 degrees C. According
      to the melting profile, the appended spermine moiety was found to affect the Tm
      only of the triple helix, but not of the subsequent melting of the underlying
      double helix. The Tm enhancing ability of the spermine-conjugate was found to be
      better than that of other polyamine-conjugates.

PMID- 8265367
TI  - The heat-shock DnaK protein is required for plasmid R1 replication and it is
      dispensable for plasmid ColE1 replication.
AB  - Plasmid R1 replication in vitro is inactive in extracts prepared from a dnaK756
      strain but is restored to normal levels upon addition of purified DnaK protein.
      Replication of R1 in extracts of a dnaKwt strain can be specifically inhibited
      with polyclonal antibodies against DnaK. RepA-dependent replication of R1 in
      dnaK756 extracts supplemented with DnaKwt protein at maximum concentration is
      partially inhibited by rifampicin and it is severely inhibited at sub-optimal
      concentrations of DnaK protein. The copy number of a run-away R1 vector is
      reduced in a dnaK756 background at 30 degrees C and at 42 degrees C the
      amplification of the run-away R1 vector is prevented. However a runaway R1 vector
      containing dnaK gene allows the amplification of the plasmid at high temperature.
      These data indicate that DnaK is required for both in vitro and in vivo
      replication of plasmid R1 and show a partial compensation for the low level of
      DnaK by RNA polymerase. In contrast ColE1 replication is not affected by DnaK as
      indicated by the fact that ColE1 replicates with the same efficiency in extracts
      from dnaKwt and dnaK756 strains.

PMID- 8265368
TI  - Functional analysis of mRNA 3' end formation signals in the convergent and
      overlapping transcription units of the S. cerevisiae genes RHO1 and MRP2.
AB  - The Saccharomyces cerevisiae genes RHO1 and MRP2 are convergently transcribed,
      with 281 base pairs separating their termination codons. Transcript mapping
      revealed at least 111 base pairs within the RHO1-MRP2 intercoding region are
      transcribed in both directions. Transplacement experiments showed distinct
      sequences of 70 nt for MRP2 and 179 nt for RHO1 were sufficient for normal mRNA
      3' end formation. The MRP2 signal functioned in either orientation, although
      relatively inefficiently in the non-native orientation. This element contains a
      polyAT sequence essential for 3' end formation in both orientations. RHO1 or MRP2
      3' end formation was not affected by overproduction or elimination of the
      complementary, natural antisense transcript. In contrast, insertion of a strong
      promoter that extended antisense transcripts beyond their normal 3' ends
      inactivated either MRP2 or RHO1. These data suggest that transcript termination
      in the compact yeast genome can be important to prevent inactivation of
      downstream genes as a result of antisense transcription.

PMID- 8265369
TI  - Restriction endonuclease NciI is not blocked by CpG methylation.

PMID- 8265370
TI  - SpoU protein of Escherichia coli belongs to a new family of putative rRNA
      methylases.

PMID- 8265371
TI  - A new protein motif found in DNA joining and DNA binding proteins.

PMID- 8265372
TI  - Nucleotide sequence variations surrounding the standard recombination junction of
      pseudorabies viruses.

PMID- 8265373
TI  - A primer extension assay for modification of guanine by Ni(II) complexes.

PMID- 8265374
TI  - Exonuclease III induced ligase-free directional subcloning of PCR products.

PMID- 8265375
TI  - A shuttle vector system for the rapid detection of recombination in murine cells.

PMID- 8265376
TI  - Preparation of pure oligonucleotide-alkaline phosphatase conjugates.

PMID- 8265377
TI  - Private function?

PMID- 8265378
TI  - Unison's night nurse. Interview by Sandra Hempel.

PMID- 8265379
TI  - Laura's legacy.

PMID- 8265380
TI  - Cooling hot potatoes.

PMID- 8265381
TI  - Autonomous practice. Joint input.

PMID- 8265382
TI  - Autonomous practice. Model methods.

PMID- 8265383
TI  - Transplants: overcoming staff fears.

PMID- 8265384
TI  - Using psychoactive drugs.

PMID- 8265385
TI  - London shake-up: hazy course ahead.

PMID- 8265386
TI  - Raising the grade.

PMID- 8265387
TI  - Opting out.

PMID- 8265388
TI  - A fight for justice.

PMID- 8265389
TI  - Patient power.

PMID- 8265390
TI  - A chance for feedback.

PMID- 8265391
TI  - Continence. Regained dignity.

PMID- 8265392
TI  - Continence. A psychological approach.

PMID- 8265393
TI  - Midwifery pays tribute to HIV specialist.

PMID- 8265394
TI  - Continence. Island education.

PMID- 8265395
TI  - Continence. Time to break the silence.

PMID- 8265396
TI  - Students' views on caring for people with AIDS.

PMID- 8265397
TI  - Behind closed doors.

PMID- 8265398
TI  - Research fodder.

PMID- 8265399
TI  - World AIDS Day. Professional help. Interview by Daloni Carlisle.

PMID- 8265401
TI  - World AIDS Day. Men at work. Interview by Paul Mangan.

PMID- 8265400
TI  - World AIDS Day. Positive thinking.

PMID- 8265402
TI  - World AIDS Day. Useful organizations.

PMID- 8265403
TI  - Making sense of reagent strip urine testing.

PMID- 8265405
TI  - Attitude problem.

PMID- 8265404
TI  - NT survey results. Workplace violence.

PMID- 8265406
TI  - Growing confidence.

PMID- 8265407
TI  - Health promotion. Back to basics.

PMID- 8265408
TI  - Nursing abroad. Operating under siege.

PMID- 8265409
TI  - Public health. A hard sell.

PMID- 8265410
TI  - Time to stop fighting.

PMID- 8265412
TI  - Computing. Point of contact.

PMID- 8265411
TI  - Computing. Deciding data.

PMID- 8265413
TI  - AIDS services to enter mainstream.

PMID- 8265414
TI  - Normal thought processes. An overview.
AB  - The complexity of the neurologic mechanisms operating in normal thought processes
      is obvious as is their impact on the quality of human life. The efficient
      performance of intellectual activity, that is, thinking and reasoning, assumes an
      awake, alert state and encompasses the interplay of fundamental mental operations
      such as attention, memory, spatial orientation, language, and higher order
      functions of insight, calculation, and abstract reasoning. Systematic assessment
      of the full range of operations is required to accurately diagnose alterations in
      thought processes, because the identification of specific impairments may
      facilitate the localization of brain injury as well as focus nursing
      intervention.

PMID- 8265415
TI  - Alteration in level of responsiveness. A proposed nursing diagnosis.
AB  - The use of physiologically derived nursing diagnoses is crucial in care delivery
      to the patient population at risk for secondary neurologic injury. Eliminating
      physiologic diagnoses has left the current taxonomic representation of nursing
      diagnoses inadequate for describing or quantifying care delivery to this patient
      population. The literature supports the premise that nursing care plays a large
      role in prevention and minimization of secondary brain injury. The proposed
      nursing diagnosis "alteration in level of responsiveness" recognizes the use of
      physiologic concepts and data and is an appropriate label to describe the nursing
      care provided to the patient at risk for secondary brain injury.

PMID- 8265416
TI  - Sensory perceptual alteration. Diagnosis, prediction, and intervention in the
      hospitalized adult.
AB  - This article proposed the nursing diagnosis SPA as the appropriate term for a
      phenomenon that has been frequently studied, described, and discussed by nurses
      and physicians using various diagnostic and descriptive labels. SPA affects
      patients, significant others, and nurses. SPA results in inflated health care
      costs because it prolongs hospitalization and increases the vigilance required by
      the nursing staff to maintain patient safety. It is also a source of emotional
      distress for the patient and his or her significant others. It has been proposed
      that alteration in NF is the primary cause of SPA. Physiologic, psychological,
      and environmental alterations represent barriers to adequate NF, thereby
      interfering with accurate perception of stimuli. A temporary adverse response
      characterized by impaired cognition and inappropriate behavior occurs. A review
      of nursing and medical literature during the last 30 years has identified a
      multitude of conditions that may precipitate SPA, thus supporting the theory that
      SPA has a multivariate. Yet, a consistent pattern or cluster of risk factors has
      not been identified. Recent data on the incidence of SPA in hospitalized patients
      are sparse, and previous research reveals inconsistency in data regarding
      incidence in all of the populations studied. This inconsistency reflects
      differences in the settings and demographic characteristics of the subjects
      studied. In addition, differences in reported incidence can also be attributed to
      methodological variations brought about by differences in terminology and
      criteria used to define and diagnose the phenomena associated with SPA. Future
      research should include reestablishing the incidence of the phenomenon in various
      populations of hospitalized patients. Populations previously overlooked in the
      investigation of SPA should also be studied. Examples include organ transplant
      patients and patients treated with cardiac-assist devices. The behavioral
      sequelae of SPA have been adequately established in the literature. Therefore,
      future research should focus on identifying those patients at risk rather than
      continuing to describe behaviors associated with SPA. The importance of risk
      identification has been discussed. Identifying patients most at risk for SPA by
      systematically screening them with a risk tool would facilitate allocation of
      resources and preventative interventions. Predictive tools need to be developed
      and tested. A risk-assessment tool could be included with the admission nursing
      history, and a daily risk assessment could be incorporated into the assessment
      documentation system. To develop risk prediction tools, it may be necessary to
      further investigate the barriers to accurate NF. Replication of prior descriptive
      studies on the causes of SPA should be attempted.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8265417
TI  - Managing the care of patients with irreversible dementia during hospitalization
      for comorbidities.
AB  - Caring for the patient with AD hospitalized with comorbidities is a nursing
      challenge. By educating staff, using the PLST model, working with families, and
      implementing patient-focused care, positive outcomes are not only possible but
      probable. It is important for staff to work with caregivers in all aspects of
      care of the patient incorporating the patient's personal and medical historical
      knowledge into the care plan. Nursing facilities and families can provide a
      wealth of information, and communication before and after hospitalization
      maximizes positive outcomes for all concerned.

PMID- 8265418
TI  - Surveillance of spinal cord motor and sensory function.
AB  - Once a primary SCI occurs, there is great potential for further deterioration in
      spinal cord function due to secondary injury processes. Deterioration in the
      function of the spinal cord needs to be detected in a timely manner so that
      interventions to limit the progression of injury can be initiated. Spinal cord
      function assessment should be thorough, systematic, easy to perform, and based on
      spinal cord structure and function. Because sensory and motor information is
      carried in different tracts, with locations in different parts of the spinal
      cord, it is important to individually assess and document the function of each
      major tract. A spinal cord surveillance tool was developed that incorporated
      motor and sensory parameters by cord segment level. The aim of developing and
      implementing the flowsheet was to improve the quality of nursing care given to
      SCI patients by providing nurses with a tool that (1) standardizes the
      assessment, (2) facilitates comparison of findings to previous assessments, and
      (3) improves communication of patient status data among health care team members.

PMID- 8265419
TI  - Assessment and management of impairments in swallowing.
AB  - Assessment of related factors and defining characteristics can assist the nurse
      to identify and refer patients with potential or actual impaired swallowing. Once
      the nature of the patient's swallowing difficulties has been confirmed, nurses
      can intervene to decrease the risk of aspiration, maintain food and fluid intake,
      and teach patients and families.

PMID- 8265420
TI  - Parkinson's disease. Quality of life issues.
AB  - PD affects many dimensions of quality of life. This article has identified motor
      and nonmotor features of PD that are directly related to a patient's quality of
      life. Medication therapy can help to ameliorate some of the symptoms, yet side
      effects can be as disabling as the symptoms of PD. Nursing care should include
      assessment, intervention, and evaluation of both physical and psychosocial
      aspects of care for patients with PD to assist them in achieving maximum
      functioning.

PMID- 8265421
TI  - Spasticity. Mechanisms and nursing care.
AB  - Spasticity is a motor dysfunction affecting persons with an UMN injury in varying
      ways. Nurses can identify spasticity in their patients by the presence of
      hyperactive DTRs and hypertonicity (increased muscle tone). Other characteristics
      often present with spasticity are clonus and spasms. Spasticity interfering with
      recreation, work, or basic activities of daily living may be decreased through
      the use of a variety of nursing interventions. Some of these interventions are
      more advantageous for spasticity caused by brain injury, whereas others are more
      helpful for spasticity caused by the spinal cord injury. Interventions research
      has begun; however, more research needs to be done to identify the most effective
      nursing measures to decrease spasticity.

PMID- 8265422
TI  - Nursing interventions for persons receiving immunosuppressive therapies for
      demyelinating pathology.
AB  - The client receiving immunosuppressive therapy for demyelinating disorders faces
      many challenges. The nurse should be involved in the constant assessment of the
      client for potential complications of the therapy as well as changes in the
      underlying disease process. Many of the nursing interventions focus on comfort
      and symptom management as well as providing information for the client and family
      to use in understanding the therapy and minimizing the effects of
      immunosuppression. Involving the family in client management will only strengthen
      the overall plan and outcomes for client care.

PMID- 8265423
TI  - HIV infections of the central nervous system. What are the nursing implications?
AB  - HIV disease attacks people without regard to age, race, gender or socioeconomic
      status, and the number of people affected continues to increase. The increased
      incidence of disease and increased length of survival will lead to a rise in HIV
      related CNS syndromes. CNS involvement adds to the complexity of the disease and
      necessitates involvement of many disciplines. The nurse is responsibility for
      facilitating and coordinating the multidisciplinary team effort. The nurse must
      also be an advocate to provide access to beneficial services and to develop
      services that are not in place. The task of nursing is to assist the person
      living with AIDS to maintain his or her quality of life however they wish to
      define it.

PMID- 8265424
TI  - Tunneled catheters. Technologic advances and nursing care issues.
AB  - Tunneled right atrial catheters have allowed more patients to benefit from
      intensive intravenous therapy regimens. The enthusiasm for increased therapeutic
      protocols and the benefit in quality of life for patients using these catheters
      must be tempered by a sincere respect for the many serious complications that can
      occur. Careful attention to aseptic technique and the use of a protocol to
      evaluate problems increase the benefits to the patient while decreasing the risk
      of serious complications.

PMID- 8265425
TI  - Implanted ports. Technologic advances and nursing care issues.
AB  - The IVAD has an established role in the care of patients requiring frequency or
      long-term vascular access. IVADs are used in all types of settings including
      hospitals, ambulatory clinics, and the home. Nurses are responsible for
      identifying patients who would benefit from an IVAD, conducting preoperative
      teaching and postoperative assessment, accessing the port, administering
      medications, performing site care, maintaining patency, teaching self-care, and
      troubleshooting. An abundance of controversial issues in the management of IVADs
      offers a wide range for potential research studies. In addition, the impact of
      evolving technology will continue to influence the care issues surrounding IVADs.
      Continual appraisal of new information is essential for nurses to remain current
      and competent in meeting the needs of patients with IVADs.

PMID- 8265426
TI  - Nursing care of patients with implanted pumps.
AB  - The implantable pump systems are totally implantable drug delivery systems
      designed for long-term infusion therapy. These systems have made it possible to
      maintain the regional delivery of cytotoxic agents and analgesics in a relatively
      safe and convenient manner for the patient. Regular maintenance is required. The
      nurse plays a key role in maintaining implantable pump systems, and he or she
      must have a thorough understanding of the systems and their various applications.
      Although these systems are complex, the discomfort and restrictions imposed on
      the patient by their use are minimal. The required maintenance is infrequent and
      simple enough to allow for greater mobility and freedom from hospitalization for
      the patient.

PMID- 8265427
TI  - Administering intraperitoneal chemotherapy using a peritoneal port.
AB  - The IP access provided by the relatively closed system using subcutaneous portals
      linked to the Tenckhoff catheter has revolutionized the clinical approach to
      intra-abdominal tumors, especially to ovarian cancer. The development of totally
      implanted peritoneal access ports that diminish the risk of infection and the
      design of treatment regimens that do not require drainage of the drugs from the
      peritoneal cavity after instillation have reduced the technical complexity of IP
      therapy. This treatment approach is safe and can be easily administered by
      trained oncology nurses and physicians in an outpatient setting. The success of a
      program for IP chemotherapy depends on a reliable and safe access to the
      peritoneal cavity, such as the port. Because of the port, during the past 13
      years IP chemotherapy has developed into an effective treatment, especially for
      ovarian cancer patients with small volume disease following laparotomy. Nurses
      have played a major role in the development of this treatment modality. They have
      become quite skillful in making assessments and intervening with appropriate
      nursing measures to ensure that a highly specialized and complex procedure is
      managed safely. Further clinical nursing research will improve the administration
      process of IP therapy and ultimately will improve the quality of life for
      patients.

PMID- 8265428
TI  - The role of fibrinolytic agents in the management of thrombotic complications
      associated with vascular access devices.
AB  - VADs have made a significant contribution to improving quality of life for
      patients requiring long-term therapies. Clearly, this means of vascular access
      has offered relief from repeated venipuncture for IV access or blood sampling.
      Reports of the incidence of associated noninfectious complications vary between
      14% and 25%. These rates are significant and warrant the development of
      strategies to manage such events. Fibrinolytic therapy offers a viable option for
      patients who have developed complications of a thrombotic nature. Although direct
      IV push administration may be relatively well accepted, many questions remain
      regarding the delivery of continuous infusions. Questions about dosing regimens,
      timing and number of administrations, and the ideal route of delivery all provide
      fertile opportunities for collaborative research.

PMID- 8265429
TI  - Issues in the management of percutaneous central venous catheters. Single and
      multiple lumens.
AB  - In this era of high technology and extensive parenteral therapies, multiple-lumen
      CVCs seem to be among the many devices needed to provide appropriate care to
      hospitalized patients. All CVCs, regardless of their benefit, create substantial
      risks for mechanical and septic complications. Antibacterial solutions that are
      bonded to the catheter and longer-acting skin antiseptics offer preliminary
      evidence that CVC sepsis rates can be reduced. The advances in CVC design,
      materials, and coatings are intended to be a supplement to--not a substitute for-
      meticulous care of CVCs.

PMID- 8265430
TI  - Intraspinal devices for pain management.
AB  - Intraspinal drug delivery is one of several important pain management therapies.
      Numerous delivery methods and drugs are available for administration into the
      epidural or intrathecal space. The choice of systems and drugs is based on the
      nature and duration of the patient's pain, his or her other medical problems, and
      patient resources. Patients must be carefully selected to ensure optimal results.
      Nurses can assist in this screening and perform preoperative teaching,
      postoperative care, and long-term follow-up. Essential knowledge includes general
      pain management principles as well as principles of intraspinal drug delivery.

PMID- 8265431
TI  - Peripherally inserted central venous catheters.
AB  - It has been estimated that 5 million central venous catheters are used in the
      United States each year. The medical market has been inundated with vascular
      access devices representing phenomenal advancement in catheter technology. These
      devices are not without serious risk, however, and they require constant
      vigilance and scrupulous care to prevent life-threatening complications. Nursing
      care and management of these devices are complex, and many controversial practice
      issues challenge nursing practitioners. The insertion of central venous catheters
      by registered nurses is a relatively new adventure in nursing practice,
      increasing our professional responsibility, accountability, and liability.
      Scientific principles and research must direct our practice and our decisions.
      The challenge is to seize this opportunity to develop a new concept in IV therapy
      based on nursing research.

PMID- 8265432
TI  - Central venous access devices. Issues for staff education and clinical
      competence.
AB  - This article reviewed some of the challenges facing nurses in an ever-increasing
      quality-minded, cost-effective health care environment. Documenting competency
      will remain a concern of high regard as healthcare faces an uncertain future. The
      call for competency comes from both outside and within the profession. The notion
      of quality care is being associated with competency directed at outcomes. Each
      professional nurse must continuously assess his or her level of competency and
      seek out education. Institutions are taking responsibility for providing
      competency education and training for their employees, including nurses, but
      employment is not a substitute for professional behavior. Ultimately, competency
      is an individual professional responsibility. This article discussed two
      different institutional-based programs for providing competency education to
      nurses caring for patients with CVADs. Although the approaches are different,
      each program supports skill development and competency documentation. The
      programs are presented to stimulate thinking and offer ideas for practice
      settings confronted with ensuring competent practitioners. The challenge for
      nurses is to maintain skill in specialty practices heavily influenced by
      technology. The challenge for institutions and agencies is to ensure competency
      while maintaining cost effectiveness.

PMID- 8265433
TI  - Equating nursing education with allied professions.

PMID- 8265434
TI  - Bone marrow aspiration.

PMID- 8265435
TI  - The cancer of politics.

PMID- 8265436
TI  - Reader calls for more research on mammography efficacy.

PMID- 8265437
TI  - Chronic sorrow: a response to living with cancer.
AB  - This study investigated the occurrence of chronic sorrow in individuals diagnosed
      with cancer and explored factors perceived as helpful to those experiencing grief
      related feelings. Using the Burke/NCRCS Chronic Sorrow Questionnaire (Affected
      Individual Version), interviews were conducted with 10 individuals with cancer at
      least one year postdiagnosis. Interviews were transcribed and coding categories
      were developed. Data then were sorted into categories and recurring themes were
      identified. Nine of the subjects demonstrated evidence of chronic sorrow.
      Subjects most often used cognitive or action-oriented coping strategies to deal
      with their grief-related feelings. Nursing roles identified as particularly
      helpful to subjects experiencing chronic sorrow were providing an empathetic
      presence and being a teacher/expert. Nurses need to be aware that individuals
      living with cancer may experience chronic sorrow, and they need to be prepared to
      intervene in ways deemed helpful.

PMID- 8265438
TI  - Neurologic complications of immunosuppressive cancer therapy.
AB  - Current therapies for cancer treatment, organ transplantation, and many
      inflammatory diseases involve the use of a variety of immunosuppressive agents,
      including antineoplastics, steroids, and cyclosporine. Direct neurotoxicities
      associated with these drugs include central nervous system disorders such as
      encephalopathy, seizure, cerebellar dysfunction, ophthalmologic and
      ototoxicities, mental status changes, and peripheral neuropathies with sensory or
      motor dysfunction. The incidence and severity of these toxicities vary and often
      depend on the dosage and schedule of administration and the presence of
      associated risk factors. Many of these neurotoxicities are reversible upon dose
      reduction or discontinuation of therapy. Important nursing measures for patients
      at risk for or experiencing neurologic complications include patient/family
      teaching, baseline neurologic assessment, monitoring response to therapy, and
      providing psychosocial support and appropriate reassurance to family members.
      This article presents an overview of neurologic complications specific to common
      immunosuppressive agents associated with cancer therapy, predisposing risk
      factors, and clinical manifestations. Nursing assessment parameters and
      management strategies also are described.

PMID- 8265439
TI  - Child-rearing concerns of parents with cancer.
AB  - A diagnosis of cancer creates multiple problems for families, including major
      changes in life-styles, relationships, communication, roles, and living patterns.
      This article describes the results of a qualitative study of child-rearing
      stressors of 13 parents: 10 patients with cancer and 3 of their spouses. Data
      were collected using open-ended interviews. The major categories derived from the
      data were parent stressors and coping strategies, and parents' perceptions of
      child stressors and coping strategies. Parent stressors were related to the
      parents' knowledge and feelings, to their children, and to parent-child
      communication. Parent coping strategies included seeking support, making
      decisions, talking with the children, making alternative childcare arrangements,
      and trying to be supportive to child and spouse. Child stressors identified by
      the parents included changes in family life-style, embarrassment over the
      parent's appearance, hospital visiting, and obtaining information. Nursing
      interventions based on the identified stressors are suggested.

PMID- 8265440
TI  - The lived experience of self-transcendence in gay men with AIDS.
AB  - This phenomenologic study described the structure of self-transcendence in eight
      gay men with AIDS. The men provided oral or written descriptions of experiences
      associated with feelings of increased interconnectedness with others, sense of
      well-being, and meaning and purpose in life. The data were analyzed using
      Colaizzi's phenomenologic technique. The men experienced self-transcendence in
      the three ways described by Frankl. Reaching out for help and helping others
      alleviated the men's sense of aloneness and isolation. Their acceptance of the
      closeness of death led to a sense of urgency to create a legacy and to
      participate only in activities that had meaning for them. Knowledge of these
      views and behaviors may help nurses to create a therapeutic exchange in which
      self-transcendent views are fostered in other gay men with AIDS.

PMID- 8265441
TI  - Camp Fresh Horizons: an innovative wellness experience for patients with cancer.
AB  - Recognizing that cancer and its treatment can negatively affect many aspects of
      an individual's functioning, the Western New York Chapter of the Oncology Nursing
      Society (ONS) designed an outdoor camping experience that allowed patients to
      refocus their lives, briefly, from disease and treatment to life and living. The
      camp, Camp Fresh Horizons, incorporated wellness-related activities designed to
      assist patients toward self-actualization. Twenty-four adults with cancer, 16 of
      their guests, and approximately 80 volunteers attended the weekend camp, which
      included indoor and outdoor recreational programs. Informal evaluations indicated
      that an experience based on wellness may offer improved emotional and physical
      functioning for people with cancer. This project proved to be a refreshing and
      different approach to patient- and family-centered support. The authors suggest
      that this wellness-centered project may be an important patient intervention
      useful to other ONS chapters.

PMID- 8265442
TI  - Survey of oral hygiene regimens among bone marrow transplant centers.
AB  - Oral complications may occur as an adverse effect of the preparative regimens
      used in bone marrow transplantation (BMT). A variety of oral-care regimens are
      used to manage the prevention and treatment of oral complications. The purpose of
      this descriptive survey was to identify similarities and differences in oral-care
      regimens among various BMT centers. A 35-item questionnaire was sent to 92 BMT
      centers, with an 80% response rate. The responses were analyzed using descriptive
      statistics. Following a variety of guidelines, routine oral assessments were
      performed by physicians (41%), nurses (33%), and dentists (25%). Thirty-eight
      percent of the BMT centers used WBC counts as a basis for changing the oral
      hygiene regimen; 90% used platelet counts. When toothbrushing was discontinued,
      50% of the centers used toothettes. In 54% of the centers, flossing was not used
      in oral hygiene regimens. The two primary mouth-rinses used were chlorhexidine
      and normal saline. In summary, few similarities existed in the assessment and
      management of oral care.

PMID- 8265443
TI  - Validity and reliability of a bone marrow transplant acuity tool.
AB  - The purpose of this project was to develop a valid and reliable patient-acuity
      tool for patients undergoing bone marrow transplant (BMT) as part of an overall
      patient-acuity system. A survey of other cancer centers and a review of the
      literature revealed no acuity tools that were designed for patients undergoing
      BMT. A four-level, nursing-diagnosis-based tool was developed with multiple
      indicators in each level, and its validity and reliability were studied. Content
      validity indexes (CVIs) were generated for each indicator by a panel of content
      experts. CVIs ranged from 0.4 to 1.0 with an overall CVI of 0.93 for the tool.
      Interrater reliability using two raters for 79 patients was high (r = 0.94, p <
      0.001). Results of the study provide sufficient evidence of validity and
      reliability to warrant use of the tool, but further study is needed.

PMID- 8265444
TI  - Factors associated with meaning in life among people with recurrent cancer.
AB  - Attribution theory proposes that negative or unexpected events challenge one's
      sense of meaning. The purpose of this correlational, cross-sectional study was to
      determine what factors were associated with the sense of meaning in life among
      people with recurrent cancer. A convenience sample of 74 subjects completed six
      survey instruments, including the Purpose in Life (PIL) Test, Symptom Distress
      Scale, Enforced Social Dependency Scale, and Psychosocial Adjustment to Illness
      Scale, as well as two surveys developed by the author to assess aspects of the
      search for meaning, and demographic and illness variables. Significant negative
      Pearson correlations were found between sense of meaning and the following
      variables: symptom distress, social dependency, and length of time since
      diagnosis of recurrence. Adjustment to illness was associated with a clear sense
      of meaning. Analysis of variance indicated that married subjects had
      significantly higher PIL Test scores than single subjects. In concert, these
      factors accounted for 38% of the variance in sense of meaning. These findings
      empirically demonstrate that the sense of meaning is integrally associated with
      the physical and psychosocial effects of illness and suggest that oncology nurses
      must understand how to care for those who search for meaning.

PMID- 8265445
TI  - Documentation of neurotoxicity resulting from high-dose cytosine arabinoside.
AB  - High-dose cytosine arabinoside or ARA-C (HDAC) has been shown to be an effective
      regimen in patients who are refractory to conventional doses. Neurotoxicity, a
      side effect associated with HDAC, has been reported in 7%-28% of patients. Both
      cerebellar and cerebral dysfunction have been reported. Neurotoxicity cannot be
      completely prevented, but a nurse's early detection of subtle changes can
      decrease toxicity severity. Assessment includes evaluating the patient's level of
      consciousness, speech patterns, vision, ocular movements, and coordination of
      upper and lower extremities. Early detection and intervention can lead to
      improved patient outcomes and enhanced quality of life. A neurotoxicity
      assessment tool and implications for its use are presented.

PMID- 8265446
TI  - Pitfalls in quality-of-life assessment: lessons from a Southwest Oncology Group
      breast cancer clinical trial.
AB  - There is increasing interest in evaluating the impact of cancer treatment and
      medical intervention on patient quality of life (QOL). This article reports the
      findings of a substudy that incorporated the Functional Living Index--Cancer in
      an ongoing adjuvant breast cancer clinical trial sponsored by the Southwest
      Oncology Group. The companion study had to be terminated prior to the end of the
      two-armed, randomized trial because of poor reporting rates over time. Problems
      with missing data items also occurred. Poor reporting rates in this trial
      motivated several recommendations for conducting QOL assessment in the
      cooperative group setting: (a) build support for QOL assessment among the group's
      leadership, (b) involve physicians and oncology nurses in the study design, (c)
      identify a QOL liaison at each participating institution, and (d) aggressively
      monitor the quality and timeliness of data submission.

PMID- 8265447
TI  - Assessing master's programs in oncology nursing.

PMID- 8265448
TI  - Guidelines assist in planning programs for poor.

PMID- 8265449
TI  - Indigent patient programs provide assistance in acquiring pain medications.

PMID- 8265450
TI  - Drug companies offer financial assistance to patients on medication.

PMID- 8265451
TI  - Strategies increase access to care in rural areas.

PMID- 8265452
TI  - [Intravenous immunoglobulins in bone marrow transplantation].
AB  - Intravenous immunoglobulins have a role also in the prevention of infections
      after a bone marrow transplantation. Even if a reduction of CMV pneumonia is
      reported it is not clear whether such an effect is due to a direct antiviral
      activity or it is mediated through an immune modulation that reduces GVHD and
      then the immune suppression. We are currently using i.v.Ig at a dose of 100
      mg/kg/day within a protocol for GVHD prophylaxis after a mismatched BMT.

PMID- 8265453
TI  - [Anti-Rh(D): an efficacious therapeutic alternative in autoimmune
      hemocytopenias].
AB  - In the last years high dose intravenous immunoglobulin (i.v.IG) has clearly
      modified the therapeutic approach toward autoimmune hemocytopenia. Their
      introduction has promoted the studies on the i.v.IG mechanisms of action: the
      hypothesis most widely accepted is the blockade of Fc-receptors in the
      reticuloendothelial system. It was hypothesized that low levels of anti-red blood
      cell antibodies contained in the i.v.IG preparations might be responsible for the
      Fc-receptor blockade. On this basis, anti-Rh(D) immunoglobulin has been
      successfully tested in Rh-positive patients with idiopathic thrombocytopenic
      purpura (ITP). The present paper describes the presumed mechanisms of action,
      clinical indications, side effects and cost of the anti-Rh(D) immunoglobulin.
      Until now, anti-Rh(D) has been chiefly employed in patients with ITP and human
      immunodeficiency virus-related ITP. However, at present, new clinical indications
      are emerging from studies in patients with autoimmune neutropenia, both using the
      intravenous and the intramuscular route. Anti-Rh(D) immunoglobulin has proved, in
      our and in other Authors' experience, a safe and easy to be administered
      treatment, at low cost and slightly lower in efficacy compared with i.v.IG.

PMID- 8265454
TI  - [Tests of autonomic nervous system functioning in children: normal values].
AB  - The study of cardiovascular autonomic reflexes is the most physiological and
      reliable test for the assessment of autonomic function: they consist of the
      analysis of variation of heart rate and arterial pressure provoked by many
      physiological stimuli. Up to now normal pediatric reference data were not
      available: we have standardized these tests in 198 normal children (94 M, 104 F),
      aged 8.3-15.7 years, without any symptom of possible autonomic dysfunction
      pathology. A complete auxological evaluation has been performed. Autonomic tests
      were performed by ECG recording and arterial pressure monitoring during normal
      and deep breathing, Valsalva manoeuvre, lying to standing postural change,
      isometric muscular contraction (sustained hand-grip and leg rising). Eleven
      autonomic parameters were obtained. Many statistical correlation between
      autonomic parameters and auxological features have been explored, without
      remarkable results. A significative difference emerged only between sexes. Normal
      reference values has been calculated. Their utility for the study of autonomic
      dysfunction is discussed.

PMID- 8265455
TI  - [Autonomic neural functioning in children with the periodic syndrome].
AB  - The pathogenesis of periodic syndrome (recurrent abdominal pain, cyclic vomiting,
      headache and other equivalents of childhood migraine) is often related in the
      literature to a "neuro-vegetative dysfunction", by which occasional stimuli
      (environmental, metabolic, emotional) should find a particular somatic
      expression. The homeostatic role of the autonomic nervous system could be
      deficient in these cases, but systematic research has never been done to explore
      this hypothesis. We have evaluated the autonomic nervous function in 38 children
      (12 M, 26 F) with periodic syndrome, by cardiovascular autonomic function tests.
      They consist of ortho- and parasympathetic parameters obtained by ECG
      registration and pressure monitoring during deep breathing, Valsalva manoeuvre,
      lying to standing postural change, sustained handgrip. In the absence of adequate
      pediatric references values, we have previously standardized these tests in a
      population of 198 healthy children (94 M, 104 F), aged 8.3-15.7 years. Results
      have been compared with our standard reference values, matching them by t-test
      for independent data: in both sexes, significant differences have been found out
      in only one of 11 parameters (p < 0.05) of the autonomic tests performed.
      Children affected by periodic syndrome reveal a reduced heart rate variation in
      transition from the early orthosympathetic phase to the late parasympathetic one
      after lying to standing passage, showing a smaller fluctuation of autonomic
      feedback systems. The physiological meaning of this result is unclear. However,
      in children with periodic syndrome no prevalence of ortho- or parasympathetic
      systems is evident.

PMID- 8265456
TI  - [Recurrent cystitis in children: do predisposing factors exist for its onset?].
AB  - It is known that a great number of subjects, mainly little girls, frequently go
      to pediatric's observation for recurrent episodes of pollakiuria, dysuria or
      burning miction. They often complain enuresis, sometimes tenesmus so intense that
      they arrive at the incontinence (urge incontinence). Many of these cases, quickly
      defined as cystitis, really revealed that they weren't. Repetitively negative
      bacteriologic examinations allow us to classify them as "sham syndromes", as
      Stephens called them. According to what we said above, we wondered whether any
      recurrent cystitis are not favoured by missed observation of definite rules.

PMID- 8265457
TI  - [Epidemiological,and physiopathological findings in retinopathy of prematurity:
      the authors' personal cases].
AB  - The authors present a retrospective epidemiological study on retinopathy of
      prematurity (ROP), performed on 738 newborns with a gestational age of 34 +/-
      2.41 weeks and birth weight of 1971 +/- 351 g. They excluded all cases with
      severe respiratory distress and other pathological conditions. First stage of ROP
      shows no correlation with gestational age and birth weight, whereas second and
      third stages of ROP show an inverse correlation with the above mentioned factors,
      particularly birth weight. Among neonates with the same gestational age, the
      incidence of ROP is higher in those "small for date". Regarding the pathogenesis
      of ROP, the authors outline the importance of perinatal hypoxia.

PMID- 8265458
TI  - [Intervertebral disk calcification in a child].

PMID- 8265459
TI  - [Lactate dehydrogenase isoenzymes in HIV-positive children].
AB  - Considering that in the HIV infection there is a precocious deterioration of
      humoral immunity with rapid turn-over of cellular B clones, we have evaluated the
      conduct of serum lactate-dehydrogenase activity (LD, EC 1.1.1.27) and its
      isoenzymes in 21 children born from HIV-positive mother respect to a control
      group (30 subjects). Furthermore we have checked the existence of a probable
      correlation between those and other clinical and immunologic parameters (total
      lymphocytes, CD4/CD8, immunoglobulins, classification according to the Atlanta
      CDC). In seropositive children we saw, respect to those evolved towards P3 stage,
      a significantly raising of LD4 (also vs. control group) for likely pulmonary
      parenchyma's damage, LD3 for B immature lymphocytes' increase and a reduction of
      LD1 (also vs. control group) for mature clones' decrement. Furthermore in
      seropositive subjects there was the existence of a direct correlation between LD1
      and CD4/CD8 values. As such, the evaluation of LD isoenzymes can establish an
      useful element in the clinical monitoring of seropositive children.

PMID- 8265460
TI  - [The asthmatic child and sports].
AB  - Many asthmatic children are more disabled by exercise-induced asthma (EIA) than
      by other asthmatic attacks. Recent attention has focused on the pathophysiology
      of EIA and its prevention. Only within the past few years the effects of exercise
      programs have been examined carefully in children with asthma. Thus, they can
      increase work tolerance and fitness with a beneficial effect of physical training
      on EIA. Adequate training intensities would be possible if EIA could be prevented
      by premedication and if a type of exercise was chosen which gave good
      cardiopulmonary training. Although swimming is their optimum sport (experience of
      authors), asthmatic children should be encouraged to embrace a full and varied
      program of sport. Many sportsmen and women who have asthma are able to compete at
      the highest level and gain olympic and world honours.

PMID- 8265461
TI  - [The prevention of caries in Alta Val di Cecina--Volterra: a longitudinal study].
AB  - The authors present the results of three years' activity relating to "caries'
      prevention" in comparison with data concerning the research of previous five
      years. The average and standard deviations of DMFT values with regard to the
      permanent teeth and dmft concerning the deciduous ones, obtained from the dental
      visit of 222 children attending the 1st and the 3rd class of the primary school
      and 1st class of the secondary school, has demonstrated a statistically
      significant reduction of caries, compared with data concerning 749 pupils of the
      same standards in the period from 1984 to 1988. This fact confirms that the
      programme defined by U.S.L. n. 15 "Alta Val di Cecina", including sanitary
      education for children of primary school with their parents and teachers, besides
      dental examinations to the filter classes, is a valid instrument to obtain the
      reduction of carious' pathology in evolutive age.

PMID- 8265462
TI  - [Intrapancreatic lipoma: a case report].
AB  - A rare case of asymptomatic pancreatic lipoma in an eleven-month-old child is
      presented. The abdominal mass was discovered occasionally during a grip episode.
      Preoperative tests proved the presence of a neoformation arising from the
      pancreas. It was multilobed, capsulated and located between colon transversus,
      spleen and stomach without infiltration of surrounding structures. The
      histological picture was that of a mature lipoma. The authors discuss the
      differential diagnosis versus other fat tumors.

PMID- 8265463
TI  - [Spontaneous and traumatic rupture of the renal parenchyma in primary obstructive
      megaureter: a report of 2 cases].
AB  - Urinary extravasation in infants may occur secondary to a variety of congenital
      obstructive uropathic conditions. This condition has been reported most often in
      infants with posterior urethral valves and pelviureteral junction obstruction. We
      present two cases of perirenal urinary extravasation from the kidney due to
      primary obstructive megaureter. Clinical presentation, evaluation and treatment
      of this rare entity are discussed.

PMID- 8265464
TI  - [Symptomatic renal candidiasis with multiple mycetomas: a case report].
AB  - Candida albicans is the most prevalent and pathogenic fungal infection of the
      urinary tract. Although fungal urinary tract infection occur less frequently than
      bacterial infections, their incidence has increased during the last decades.
      Parenteral nutrition, corticosteroids, immunosuppressive drugs and prolonged
      antibiotic therapy are often predisposing factors. We report a case of renal
      pelvic fungus balls in a 6-month old female who developed candidal infection
      after surgical treatment for bilateral vesico-ureteric reflux; the renal
      candidiasis was treated successfully with fluconazole.

PMID- 8265465
TI  - [Habitual vomiting due to dust mite allergy. A case report].
AB  - It has been demonstrated that: a) part of the inhalant allergenic particles we
      normally breath, adhere to the oropharyngeal mucosa, and eventually progress to
      the gastrointestinal tract; b) digestive tract mucosa is able to produce specific
      IgE against aeroallergens even before than respiratory tract mucosa. The case is
      described of a 5-year-old girl who presented a daily vomiting since she was 6
      months. All clinical instrumental and laboratory findings had been unable to
      reach a definite diagnosis. SPT (inhalants and foods): Dermatoph. pteronyssinus:
      + (confirmed by RAST). The patient had an immediate, complete recover just
      following the clinician's instruction for HDM domestic prevention. Symptoms
      appeared again in response to a NPT performed with Dermatophagoides extract. The
      positivity of the exclusion-re-exposure test confirmed the diagnosis of HDM
      induced gastrointestinal allergic syndrome, so far not described in literature
      (to my knowledge). Immunological considerations: since it is known that patients
      allergic to HDM do not usually present a specific IgE-mediated gastrointestinal
      allergic syndrome, it is suspectable that an immunological tolerance can be
      instaured toward inhalant allergens as it normally happens toward food allergens.
      In atopic individuals there is a high expression of ICAM-1, VCAM-1 and other
      adhesion molecules on the surface of HEV at BALT level. Adhesion molecules
      expression and immunocompetent cells activation are modulated by several
      mechanisms among which the cytokine network plays a major role. The author
      speculates that sensitized lymphocytes may migrate from intestinal to bronchial
      mucosa, via lymphocytic immunoallergic competence. In the described clinical case
      this mechanism did not work.

PMID- 8265466
TI  - [An ovarian mass in childhood: a case report].
AB  - Ovarian tumors are a very heterogeneous group of neoplasms that rarely occur in
      pediatric age. When it happens, they are usually very malignant germ cell tumors
      such as embryonal carcinoma, endodermal sinus tumor or choriocarcinoma. We
      describe a case of a 14 years old girl who came to our observation because of an
      abdominal enlargement without others symptoms. The abdominal palpation revealed a
      big, round, painless mass from pelvic to epigastric region. A specific and
      accurate diagnosis was made by ultrasound. The histological examination of the
      surgical removed mass revealed a mucous cystadenoma that's a benign epithelial
      ovarian tumor.

PMID- 8265467
TI  - [The Silver-Russell syndrome].
AB  - The authors describe a case of Silver-Russell Syndrome with severe deficit
      growth. They display the major and minor features of the syndrome, and discuss
      about the possible pathogenetic causes.

PMID- 8265468
TI  - [The hospital admission: what damages to the child?].

PMID- 8265470
TI  - Continuing medical education in Turkey.

PMID- 8265469
TI  - [The environment and health protection of the child].
AB  - The authors outline the relationship between environment and children health
      care. They describe the environmental situations able to produce damages to the
      children's health.

PMID- 8265471
TI  - 'Common trunk' in medicine in the European community.

PMID- 8265472
TI  - Surgical common trunk training in Europe.
AB  - There are wide variations of surgical common trunk training programmes among
      European countries. Variations are also found in entry criteria to training
      programmes, in training evaluation methods and final certification, and also in
      accreditation of training institutions. Finally manpower control should be
      applied to secure production of an adequate number of competent surgeons and
      consequently high quality of health care.

PMID- 8265473
TI  - Medical education--a look into the future.

PMID- 8265474
TI  - Current problems in training arrangements in internal medicine in France.

PMID- 8265475
TI  - Current problems in training arrangements in internal medicine in Switzerland and
      Germany.

PMID- 8265476
TI  - Current problems in training arrangements in internal medicine in the Low
      Countries.

PMID- 8265477
TI  - Current problems in training arrangements in the Iberian countries.

PMID- 8265478
TI  - Monospecialty initiatives in general practice.

PMID- 8265479
TI  - Monospecialty initiative in anaesthetics.

PMID- 8265480
TI  - Monospecialty initiatives in public health.

PMID- 8265481
TI  - Monospecialty initiatives in radiotherapy.

PMID- 8265482
TI  - Overview of function of the ACMT. Advisory Committee on Medical Training.

PMID- 8265483
TI  - European boards.

PMID- 8265484
TI  - Research and development in medical education in The Netherlands.

PMID- 8265485
TI  - The nature of research and development in medical education in the UK.

PMID- 8265486
TI  - Continuing professional education.

PMID- 8265487
TI  - Educational assessment of clinical diagnostic skills: studies across Europe on
      acute abdominal pain.

PMID- 8265488
TI  - Educational implications of the development of a common health record
      architecture for Europe--the Good European Health Record project.

PMID- 8265489
TI  - Age-dependent changes in oviposition pattern and egg production traits in the
      domestic hen.
AB  - Effects of aging on oviposition pattern and egg production traits were studied
      based on records made between age at first egg and 130 wk of age in 479 hens from
      three selection lines. During the 1st laying yr (age at first egg to 71 wk of
      age), all three lines produced equal amounts of egg mass. A significant (P < or =
      .05) difference in total egg mass production (age at first egg to 130 wk of age)
      was found between a White Leghorn line selected for egg mass and a Rhode Island
      Red line selected for egg mass and feed consumption. The mean intrasequence
      oviposition interval increased significantly (P < or = .001) with age. The early
      mean intrasequence oviposition interval was not considered to be a good predictor
      of egg production traits later in life. Three explanations for decreased
      production with increasing age were found: 1) Oviposition intervals within
      sequences increased, resulting in shorter sequences and more frequent pause days;
      2) the frequency of missing eggs within sequences increased; and 3) more than 1
      pause day occurred between sequences.

PMID- 8265490
TI  - Self-selection among diets differing in methionine content by chickens of
      different lines.
AB  - Two trials were conducted to compare the ability of chickens from different
      genetic lines to select among diets differing in methionine. In Trial 1, chicks
      from White Plymouth Rock (HW) and White Leghorn (HA) lines were offered a choice
      of diets containing .85, .58, or .44% methionine from 1 through 7 days of age. In
      Trial 2, a slow-growing line of White Plymouth Rocks (LW) was used in addition to
      the same lines used in Trial 1. A choice of the three diets was offered from 1
      through 13 and from 20 through 23 days of age. During the period from 14 through
      19 days of age, all chicks were fed the .44% methionine diet. In both trials,
      Line HW chicks first exhibited a dietary preference at 5 days of age. Line HA
      chicks did not discriminate among diets in either trial when given a choice from
      1 day posthatch. They did, however, exhibit a preference starting on Day 20 in
      Trial 2 (after being fed the deficient diet). No dietary preferences were
      exhibited by chicks from Line LW. Results of these trials showed that selection
      among diets varying in methionine content was influenced by genotype, age,
      nutritional state of the chick, and their interactions.

PMID- 8265491
TI  - Divergent selection for body weight and yolk precursor in Coturnix coturnix
      japonica. 9. Evaluation of traits associated with onset of sexual maturity.
AB  - An experiment was conducted to compare traits associated with onset of sexual
      maturity in Japanese quail lines. Lines divergently selected for high and low 4
      wk BW (HW and LW), and high and low total plasma phosphorus at beginning of lay
      (HP and LP) were compared with a randombred line (RBC1) that served as the base
      population for HW, LW, HP, and LP. The HW sublines (HW-HP and HW-LP) and LP
      subline (LP-HW) were also compared to their respective line of origin. Most of
      the differences observed for males selected for a single trait were found for
      weight-selected rather than for phosphorus-selected lines. The patterns of
      significance closely followed differences expected due to the extreme diversity
      in BW for the HW and LW when compared with RBC1. Females generally matured
      approximately 2 wk later than males for HW, HP, and LP. Line LW females matured
      approximately 4 wk later than LW males. Differences were observed for variables
      associated with onset of sexual maturity for HW, LW, and HP when compared with
      RBC1. Observed changes in carcass variables for sublines were generally
      associated with reductions in BW for HW-HP, and HW-LP versus HW and for increases
      in BW for LP-HW versus LP. The differences were likely due to the fact that two
      trait selection (BW for males and total plasma phosphorus in females) has allowed
      weights to diverge when compared with lines selected for single traits.

PMID- 8265492
TI  - The relationship between various indices of carcass growth and development and
      reproduction in turkey hens.
AB  - Growth and carcass development measures were compared in turkey hens from a line
      selected for egg production (E line) and a line selected for BW at 16 wk (F
      line). Hens in both lines reached their maximal BW 4 wk after photostimulation.
      Maximal BW in F line hens was 20% greater than their respective BW after 89 days
      of production compared with only a 12% difference in E line hens. In both lines,
      there was a decline in BW through 49 days of production but no further decreases
      at 89 days. The same trend was observed for both the absolute or relative weights
      of the abdominal fat pad. The weight of the oviduct was near maximal size in E
      line hens near the onset of production, whereas it continued to increase in size
      in F line hens through 49 days of production. The same was true for liver weight
      in F line hens, whereas in E line hens liver size continued to increase
      throughout the experiment. Carcass DM and lipid were higher and carcass protein
      lower in F line compared with E line hens near the onset of lay. In a second
      experiment, heavy weight hens were fed the standard Ohio Agricultural Research
      and Development Center breeder diet or a diet with supplemental fat and increased
      ME. There were no significant diet effects on BW or egg production, but hens fed
      the high-fat, high-energy diet did have increased carcass protein (percentage DM;
      P < .08).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265493
TI  - Response of broiler breeder females to feed restriction below recommended levels.
      3. Characterizing the onset of sexual maturity.
AB  - The objective of this study was to characterize how the physical attributes
      associated with sexual maturity would be affected by feed allocation as female
      broiler breeders passed through the pullet-layer transition period. Treatments
      consisted of five feeding programs, or body weight goals, during the period of 0
      to 20 wk of age. Those were 8% above breeder standard, standard (primary breeder
      recommended body weights), and 8, 16, and 24% below standard. The characteristics
      measured included body and fat pad weights, pubic spread, comb development, head
      score (comb and wattle appearance), shank length, total plasma lipid
      concentration, ovary weight, oviduct weight, bursa of Fabricius weight, and age
      at sexual maturity. The generalized effect of increased severity of the feed
      restriction programs was to delay the birds' development without altering their
      ultimate physiological values. The exceptions to this were relative body weight
      and shank length after maturity, which were reduced in the most severely
      restricted birds. Measurements of pubic spread and comb growth and subjective
      scores of head appearance would be useful and easily obtained information when
      estimating the progression of a flock toward sexual maturity.

PMID- 8265494
TI  - Anticoccidial efficacy of semduramicin. 1. Evaluation against field isolates by
      dose titration in battery tests.
AB  - Semduramicin (AVIAX), a novel polyether ionophore, was titrated in a series of
      five battery tests at 20, 25, and 30 ppm in feed to determine the optimum level
      for use. Twelve-day-old broiler chicks were medicated for 48 h prior to
      inoculation in each 9-day test. The inocula included monospecific field isolates
      of Eimeria tenella, Eimeria brunetti, Eimeria necatrix, and Eimeria maxima, and a
      mixture of these species with Eimeria acervulina and Eimeria mitis. The numbers
      of oocysts inoculated were selected after titration of each species and the
      mixture of species. All three concentrations of semduramicin significantly (P <
      .05) reduced coccidiosis mortality and lesion scores and achieved lower feed:gain
      ratios and greater weight gains than the infected, unmediated treatments. A
      concentration of 25 ppm semduramicin was determined to be optimal based on
      improved lesion control compared with 20 ppm and improved weight gain compared
      with 30 ppm.

PMID- 8265495
TI  - Anticoccidial efficacy of semduramicin. 2. Evaluation against field isolates
      including comparisons with salinomycin, maduramicin, and monensin in battery
      tests.
AB  - The efficacy of semduramicin (AVIAX), a novel polyether ionophore, was profiled
      in a series of 57 battery tests conducted in the United States and the United
      Kingdom. The studies employed mixed and monospecific infections of Eimeria
      acervulina, Eimeria mivati/Eimeria mitis, Eimeria brunetti, Eimeria maxima,
      Eimeria necatrix, and Eimeria tenella derived from North American and European
      field isolates. Ten-day-old broiler cockerels in pens of 8 to 10 birds were
      continuously medicated in feed beginning 24 h before challenge in tests of 6 to 8
      days' duration. At the use level of 25 ppm, semduramicin effectively controlled
      mortality, lesions, and weight gain depression that occurred in unmedicated,
      infected controls for all species. In comparison with 60 ppm salinomycin,
      semduramicin significantly (P < .05) improved weight gain against E. brunetti and
      E. tenella, lesion control against E. brunetti and E. maxima, and the control of
      coccidiosis mortality against E. tenella. Salinomycin was superior (P < .05) to
      all treatments in maintenance of weight gain and control of lesions for E.
      acervulina. Maduramicin at 5 ppm was inferior (P < .05) to semduramicin in
      control of E. acervulina and E. maxima lesions, but was superior (P < .05) to all
      treatments in maintenance of weight gain and control of lesions in E. tenella
      infections. The data indicate that semduramicin at 25 ppm is well tolerated in
      broilers and possesses broad spectrum anticoccidial activity.

PMID- 8265496
TI  - Location of Salmonella typhimurium during incubation and hatching of inoculated
      eggs.
AB  - Location of Salmonella during hatching of broiler chicks was studied in three
      experiments. Unincubated, fertile hatching eggs heated to 42 C were inoculated by
      immersion for 15 min in a 16 C physiological saline solution containing
      approximately 1 x 10(5) cfu/mL of a nalidixic acid-resistant strain of Salmonella
      typhimurium. All eggs were sanitized externally by wiping with a paper towel wet
      with 70% ethanol. When incubating eggs were transferred to a hatcher, each was
      placed in a closed paper bag to minimize cross-contamination. Unhatched eggs were
      sampled by cutting away the shell over the air cell, sanitizing the inner air
      cell membrane with 70% ethanol, and removing the contents through the membrane.
      Shells and membranes were crushed and mixed in 10 mL buffered peptone (BP). Yolks
      were dissected out, dipped in 70% ethanol, and mixed with 10 mL BP. Embryos or
      chicks and all surrounding fluid were rinsed in 100 mL BP. A total of 172 eggs
      was sampled. Shells and membranes were 100% Salmonella-positive 30 min after
      inoculation, but only 38% were positive after 17 to 21 days of incubation. No
      chick rinses were positive before pipping, but 15% were positive after pipping.
      Yolk samples were 2% positive before pipping versus 8% after pipping. A majority
      of chicks hatching from positive shells and membranes were Salmonella-negative.

PMID- 8265497
TI  - Effect of induced molting on the recurrence of a previous Salmonella enteritidis
      infection.
AB  - Previous work in the authors' laboratory had shown that hens infected with
      Salmonella enteritidis (SE) during the feed removal phase of an induced molt shed
      significantly more SE and more readily transmitted SE to uninfected hens in
      adjacent cages when compared with unmolted hens. A study was conducted to examine
      the effect of induced molting on the recurrence and horizontal transmission of a
      previous SE infection. Hens aged 59 and 69 wk in Trials 1 and 2, respectively,
      were infected with SE and then molted 21 days later. In Trial 1, more molted hens
      were SE-culture-positive on Days 38 (P < or = .005) and 45 (P < or = .005)
      postinfection, and these hens shed more SE on these days (P < or = .05 and P < or
      = .005, respectively) than unmolted hens. Horizontal transmission of SE to
      previously uninfected but contact-exposed hens in adjacent cages was also higher
      in the molted group than the unmolted group on Days 38 (P < or = .05) and 45 (P <
      or = .001). Molted, contact-exposed hens also shed significantly more SE than
      unmolted hens. In Trial 2, the molted infected hens shed progressively more SE
      than the unmolted hens but the differences were not significant. However, more
      molted contact-exposed hens became SE-positive at Day 31 (P < or = .05) and 38 (P
      < or = .005) and also shed more SE on these days (P < or = .05 and P < or = .01),
      respectively) than the unmolted hens. Serum and intestinal antibody titers to SE
      were also examined in Trial 2. Molting appeared to exert no effect on the serum
      SE titers, but antibody titers in the alimentary tract were lower in the molted
      hens than the unmolted hens on Days 45 (P < or = .005) and 52 (P < or = .05). In
      Trial 1, three of eight molted directly infected hens and two of eight molted
      contact-exposed hens produced any SE-contaminated eggs. In Trial 2, no SE
      contaminated eggs were produced.

PMID- 8265498
TI  - Effect of dietary protein and selected antioxidants on fatty liver hemorrhagic
      syndrome induced in Japanese quail.
AB  - The effects of CP and antioxidants on fatty liver hemorrhagic syndrome (FLHS) in
      Japanese quail hens were studied. In Experiment 1, four treatments were arranged
      as a 2 x 2 factorial; dietary CP (18 or 24%) and reduced glutathione (GSH, 0 or
      120 mg/kg diet) were the major variables, but cysteine and other amino acids were
      higher in the 24% CP diets. Negative control (NC1) and positive control (PC1)
      diets were also evaluated. In Experiment 2, the effects of vitamin E (VE) and GSH
      were evaluated in the presence and absence of adequate dietary sulfur amino
      acids. Negative control (NC2) and positive control (PC2) diets were used. In both
      experiments, liver hemorrhage was most severe in quail fed the diets that were
      formulated to induce hepatic steatosis and limit oxidant defense capability.
      Liver hemorrhage was least severe in quail fed the diets that were formulated to
      minimize liver lipid accumulation and support oxidant defenses. Histological
      evaluation of affected quail livers showed changes consistent with FLHS in
      chicken hens. In Experiment 1, neither CP concentration nor GSH supplementation
      influenced liver hemorrhage. In Experiment 2, liver hemorrhagic score was reduced
      from 3.8 to 2.7 (P < or = .05) by adding VE to the basal diet. The PC2 diet
      further depressed liver score to only 2.0 (P < or = .05). The data clearly show
      that Japanese quail are susceptible to FLHS and indicate that a combination of
      lipotropic and antioxidant nutrients is protective against hemorrhage, even when
      lipogenic demands are maximized by feeding diets devoid of added fat.

PMID- 8265499
TI  - The effect of dietary phytase on growth performance and phosphorus utilization of
      broiler chicks.
AB  - Two experiments were conducted to evaluate the effect of dietary phytase and
      increasing levels of available phosphorus (P(av)) on the growth performance and
      phosphorus metabolism of broiler chicks. In both experiments, graded levels of P
      provided by dicalcium phosphate and of phytase were added to a low-P corn-soybean
      meal basal diet. In Experiment 1, diets providing .21, .29, .37, and .44% P(av)
      without phytase; .21% P(av) plus .05, .10, or .30% phytase; and .29% P(av) plus
      .10% phytase were each fed to four groups of seven chicks, 3 days of age. In
      Experiment 2, diets providing P(av) levels of .32, .38, and .44% and phytase
      levels of .5, 1.0, and 1.5% (250, 500, and 750 units/kg) in a factorial
      arrangement were each fed to four groups of eight chicks, 5 days of age. In
      Experiment 1, increasing dietary P(av), but not phytase, increased feed intake,
      weight gain, feed conversion, plasma inorganic P, tibia and toe ash, and tibia
      breaking strength (P < or = .05). Plasma inorganic P responded quadratically to
      increasing dietary phytase. In Experiment 2, feed intake and weight gain were
      increased by elevating the level of P(av), but not by phytase. Toe and tibia ash
      and plasma inorganic P were increased by dietary phytase and increasing levels of
      P(av) (P < or = .01). Tibia breaking strength was improved (P < or = .05) by
      dietary phytase but not by increasing levels of P(av). The P excretion was
      elevated (P < or = .01) by increasing levels of P(av) and was decreased by
      supplemental phytase (P < or = .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265500
TI  - Evaluation of the protein to energy ratio concept in broiler and turkey
      nutrition.
AB  - The main objective of feed formulation should be to maximize profits, the
      difference between returns (growth response) and costs [feed intake (FI)]. For
      broilers and growing turkeys it is necessary to predict the BW and feed intake
      responses in order to estimate which protein and energy levels maximize profits
      for the producer. Data from the literature were collected to evaluate whether
      growth and FI responses can be better predicted from the dietary protein to
      energy ratio than protein and energy levels. The Ordinary Least Squares method
      was applied to estimate the coefficients (Bn) of each model. The best model was
      selected through the J-test. The protein to energy ratio model was not selected
      in any case by the J-test. The model based on the protein and energy levels was
      selected by the J-test to predict the BW response in eight out of nine cases and
      to predict FI in six out of nine cases. A nested selection was performed to find
      models for each data set that only include coefficients that are significantly
      different from zero. The nested selection showed that BW and FI responses can be
      predicted successfully from protein and energy levels with coefficients of
      determination between .79 and .97 for broiler chickens and between .45 and .65
      for turkeys. Nutritionists should consider the use of models, like the protein
      and energy levels model, that explain and predict BW and FI responses. Future
      modeling research should consider important factors in broiler production, like
      age, sex, and temperature.

PMID- 8265501
TI  - Effects of dietary boron supplementation on broilers.
AB  - Two experiments were conducted with a total of 432 broiler chicks to investigate
      the influence of supplementing different amounts of boron to practical corn
      soybean meal diets. The birds were housed in batteries and had free access to
      feed and water. In Experiment 1, 144 1-day-old broiler chicks were fed a basal
      diet supplemented with 0, 5, 40, 80, or 120 ppm boron for 21 days. Female body
      weight was not influenced by the dietary treatments. However, males supplemented
      with 5 ppm boron were heavier and their tibias resisted more load than the
      control birds. Overall feed conversion was not influenced by boron. In Experiment
      2, 288 1-day-old broiler chicks were fed a basal diet supplemented with 0, 60,
      120, 240, or 300 ppm boron for 22 days. Male and female body weights of the 300
      ppm group were lower than those of the control birds. Percentage tibia ash was
      highest with 300 ppm boron. No significant differences were found in intestinal
      tract weight (grams of intestine per 100 g body weight) among treatments. Boron
      concentration in the breast muscle and liver increased as dietary concentration
      of boron increased. Data collected in these two experiments indicated that
      consumption of diets containing up to 240 ppm boron from hatch to 21 days of age
      was not detrimental to broiler performance. Data were not conclusive on the need
      for supplemental boron in broiler diets based on corn and soybean meal.

PMID- 8265502
TI  - An evaluation of a rinse procedure using sodium bicarbonate and hydrogen peroxide
      on the recovery of bacteria from broiler carcasses.
AB  - A patent entitled "Reduction of Bacteria Count on Poultry Being Processed into
      Food at a Poultry Processing Plant" (U.S. Patent No. 4,683,618) claimed that a
      three-step rinse process using sodium bicarbonate and hydrogen peroxide solutions
      would remove bacteria from the surface of broiler carcasses. In three replicate
      trials, 40 broilers were obtained postchill from a commercial processing plant.
      Broilers (n = 20) were treated according to the patent by spraying the inside and
      outside surfaces of each carcass with a 2% NaHCO3 solution for 5 s and rinsing
      with water, repeating, spraying with a 3% H2O2 solution for 5 s, and rinsing a
      final time with water. Controls (n = 20) were treated identically except that in
      each of the rinse steps tap water was used in place of the test solutions. Whole
      carcass rinses were conducted and total aerobic plate counts (TPC) and impedance
      detection times (DT) were determined after 1 h and 7 days at 4 C. The NaHCO3 +
      H2O2 treatment resulted in no significant difference in TPC at 1 h post-treatment
      but did result in lower TPC after 7 days and greater DT at both 1 h and 7 days.
      The procedure was effective in reducing the recovery of bacteria at 7 days post
      treatment by .3 log10 but was not effective in removing the bacteria to the
      extent implied in the patient. Based on previous studies using H2O2, these
      results are not unexpected, but commercial applicability remains questionable
      based on actual reduction levels.

PMID- 8265503
TI  - Research note: interactive effects of sodium zeolite A and Eimeria acervulina
      infection on growth and tissue minerals in chicks.
AB  - Two experiments were conducted to assess the interactive effects of dietary
      sodium zeolite A (SZA) and experimental Eimeria acervulina infection on growth
      and tissue mineral concentrations in chicks. The average initial weight of the
      chicks was 71.8 g, and the experimental periods were from 5 to 15 days
      posthatching. In both experiments, the corn-soybean meal basal diet was
      supplemented with 0 or .75% SZA and fed to uninfected chicks or to chicks
      infected with 4 x 10(5) sporulated E. acervulina oocysts on Days 0, 3, and 6 of
      the experiments. Both coccidial infection and SZA reduced (P < .05) gain and feed
      intake; however, feed efficiency was reduced (P < .01) only in the coccidiosis
      infected chicks. Neither SZA nor the coccidial infection affected (P > .10)
      plasma Ca or P, tibia P, liver Ca, Zn, Fe, or Mn, or pancreas Cu. Sodium zeolite
      A increased (P < .05) plasma Zn but only in uninfected chicks (SZA by
      coccidiosis, P < .10). The coccidial infection decreased (P < .02) tibia ash
      percentage. Sodium zeolite A decreased tibia Ca in uninfected chicks but
      increased tibia Ca in coccidiosis-infected chicks (SZA by coccidiosis, P < .10).
      The coccidial infection increased (P < .05) tibia Mg, Cu, Fe, Pb, Mn, and Al
      concentrations. Dietary SZA also increased (P < .02) tibia Zn, Mn, and Al
      concentrations. The coccidial infection decreased (P < .02) tibia Zn
      concentration, and SZA decreased (P < .05) tibia Mg and Fe. Sodium zeolite A by
      coccidiosis interactions (P < .10) were evident in tibia Zn, Fe, Mn, and Al
      concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265504
TI  - Research note: effect of tu-chung leaf (Eucommia ulmoides) on egg production
      performance, egg quality, and fat metabolism in laying hens at a late production
      stage.
AB  - The effects of tu-chung leaf (Eucommia ulmoides) supplementation on egg
      production performance, egg quality, and fat metabolism were investigated in
      laying hens at a late production stage. White Leghorn laying hens at 20 mo of age
      were provided ad libitum access to a practical diet with or without tu-chung leaf
      supplement for 3 mo. During the experimental period, egg production rate, egg
      weight, and feed intake were recorded every day. Egg samples from the last 3 days
      were collected to measure Haugh units and cholesterol concentration in the egg
      yolk. Plasma cholesterol concentration and abdominal fat weight were also
      determined. The results showed that no significant improvement in egg production
      was observed with tu-chung leaf addition. No significant effect of tu-chung was
      observed on Haugh units, plasma cholesterol, or egg yolk cholesterol, whereas
      abdominal fat weight was greater in hens fed the tu-chung diet than in those
      given the unsupplemented control diet. It was concluded that the beneficial
      effects of tu-chung leaf supplementation on egg production performance and egg
      quality were ambiguous and of little practical significance.

PMID- 8265505
TI  - Feigned infertility.

PMID- 8265506
TI  - Childhood diabetes.

PMID- 8265507
TI  - Safety and the place of birth.

PMID- 8265508
TI  - Contracts, tax, and the law.

PMID- 8265509
TI  - Survivors of childhood sexual abuse.

PMID- 8265510
TI  - Preparation strategies.

PMID- 8265511
TI  - Cystic fibrosis.

PMID- 8265512
TI  - The resurgence of TB.

PMID- 8265513
TI  - Fibrosing alveolitis.

PMID- 8265514
TI  - Who needs prescribing advisers?

PMID- 8265515
TI  - No effect of the 5HT2-antagonist ICI 169,369 on systolic, ergotamine-induced
      blood pressure changes in man.
AB  - The 5HT-antagonistic effect of drugs in man is difficult to study because of side
      effects to 5HT. Ergotamine, however contracts human arteries, probably by acting
      on 5HT receptors. This effect can be antagonized in vitro by the 5HT antagonist
      ICI 169,369. After an initial ergotamine challenge to select responders to
      ergotamine, 10 selected volunteers were given in a double blind study an oral
      dose of either placebo, 30 mg or 120 mg of ICI 169,369. After 2 hr an intravenous
      dose of 0.5 mg ergotamine tartrate was given. From 6 to 8 hr after the
      administration, ergotamine caused a mean decrease in the toe-arm systolic
      gradient, measured by strain-gauge plethysmography of 32 mmHg (P < 0.001), which
      was not influenced by either 30 mg or 120 mg ICI 169,369 (P < 0.4). The most
      likely explanation for our inability to detect any effect of ICI 169,369 on blood
      pressure changes, induced by ergotamine may be high binding (99%) of ICI 169,369
      to plasma proteins. There was, however, indication of a per se vasodilatory
      effect of ICI 169,369 since the dose of 120 mg increased the toe-arm systolic
      gradient by 4.7 mmHg.

PMID- 8265516
TI  - Comparison of cumulative and non-cumulative administration of vasoactive agents
      in arterial smooth muscle responses in vitro.
AB  - Two methods of determining concentration-response curves were compared in
      isolated endothelium-intact mesenteric arterial rings from Wistar rats: arterial
      contractile and relaxation responses were elicited by adding compounds
      cumulatively or introducing a single concentration at a time (non-cumulative
      method). The contractile responses induced by high concentrations of K+ (20-125
      mM) were comparable between the two methods, whether or not the responses were
      elicited in the presence of phentolamine (10 microM) and atenolol (10 microM).
      Noradrenaline (1 nM-10 microM) likewise induced similar contractions regardless
      of method of administration, the only exception being the highest concentration
      (100 microM) which produced lower contractile force when added directly upon
      resting tension than after cumulative administration. This difference was
      abolished by atenolol (10 microM). Arterial smooth muscle relaxations induced by
      endothelium-dependent (acetylcholine 1 nM-10 microM) and -independent agents
      (nitroprusside 1 nM-1 microM, isoprenaline 10 nM-100 microM) were similar whether
      the relaxants were added in a cumulative fashion or in a single concentration
      introduced upon each precontraction. Thus, cumulative and non-cumulative
      administration of contractile and relaxing agents give quite comparable results.
      We conclude that the cumulative method is a reliable and time-saving way of
      studying vascular smooth muscle responses in vitro.

PMID- 8265517
TI  - Involvement of opioid receptors in shaking behaviour induced by paraquat in rats.
AB  - Paraquat (30-70 mg/kg intraperitoneally) caused typical shaking behaviour in rats
      in a dose-dependent manner. Myoclonus also appeared after the shaking behaviour
      in several rats treated with the highest dose of paraquat. Morphine (5 mg/kg
      intraperitoneally, 30 min. before paraquat) significantly reduced the frequency
      of shaking behaviour. The alleviation by morphine disappeared when naloxone (1.5
      mg/kg intraperitoneally 15 min. after morphine) was coadministered. Although
      there was no histological change in brain slices of paraquat-treated rats (70
      mg/kg intraperitoneally), the fluorescein uptake into brain was increased by the
      treatment. Morphine prevented the increase of fluorescein uptake, but naloxone
      failed to antagonize this effect. On the other hand, intracerebroventricularly
      administered paraquat (25.7 micrograms/rat) caused tremor in all rats, but not
      shaking behaviour nor myoclonus. These findings suggest that paraquat
      administered systemically as well as centrally may be toxic to the brain.
      Although the actions of paraquat on the brain seem to be complicated, opioid
      receptors may play a role in the actions.

PMID- 8265518
TI  - Gamma-vinyl GABA decreases voluntary alcohol consumption in alcohol-preferring AA
      rats.
AB  - The effect of a GABA transaminase inhibitor, gamma-vinyl GABA, on the voluntary
      alcohol consumption of alcohol-preferring AA rats produced by selective breeding
      for high alcohol preference, was studied. The rats were first trained to
      voluntarily drink 10% (v/v) ethanol solution until their ethanol consumption
      stabilized. Gamma-vinyl GABA (100, 200 or 500 mg/kg) was then injected
      intraperitoneally in three groups of rats, with saline-injected animals serving
      as a control group. The rats continued to have a free choice between 10% ethanol
      and plain tap water for five days after the injection, and their ethanol, water
      and food consumptions were measured daily. Gamma-vinyl GABA decreased ethanol
      consumption by the rats in a dose-dependent way. The consumption remained
      significantly decreased for three days in the two groups receiving the highest
      doses, with only a small concomitant tendency to decreased food intake. The
      results suggest that an increase in brain GABA concentration decreases alcohol
      drinking, possibly through potentiation of the pharmacological action of ethanol.

PMID- 8265519
TI  - Pharmacokinetics of R(+)-terodiline given intravenously and orally to healthy
      volunteers.
AB  - (+)-Terodiline was given orally (25 mg) and intravenously (12.5 mg) to eight
      healthy volunteers. The pharmacokinetics of (+)-terodiline could be described by
      a one compartment model. The lag time of absorption was 0.6 +/- 0.5 hr (mean +/-
      S.D.), the absorption half-life 0.9 +/- 0.5 hr, the time to maximum serum
      concentration 5.6 +/- 2.2 hr and the corresponding maximum serum concentration 62
      +/- 22 micrograms/l. The volume of distribution was found to be 372 +/- 84 1, the
      systemic clearance 86 +/- 29 ml/min., the mean residence time 81 +/- 38 hr and
      the observed terminal half-life of elimination 56 +/- 26 hr. The urinary
      excretion of the intravenous dose was 12 +/- 6% and the renal clearance 10 +/- 5
      ml/min. The bioavailability of (+)-terodiline was 93 +/- 19%. The present results
      indicate that (+)-terodiline as well as the racemate can be characterized as low
      clearance long half-life drugs. One subject was a poor hydroxylator of
      debrisoquine and exhibited a 3-fold decrease in clearance and increase in half
      life of (+)-terodiline relative to extensive metabolizers. Observed
      pharmacological effects were mild accomodation disturbances and dry mouth, i.e.
      the same effects as those that may be seen at a corresponding dose of terodiline
      given as a racemic mixture.

PMID- 8265520
TI  - ATP leakage from ELD cells after exposure to stearic, monochlorostearic,
      dichlorostearic, and oleic acids.
AB  - The capacity of stearic, monochlorostearic, dichlorostearic and oleic acids to
      cause membrane damage was measured as their ability to induce leakage of
      adenosine triphosphate (ATP) from mammalian tumour cells in vitro. Chlorinated
      stearic acids, and oleic acid, caused ATP leakage at lower concentrations than
      normal stearic acid. The membrane disturbing properties are suggested to be a
      result of the different molecular geometries of the chlorinated stearic acids,
      and oleic acid, compared to non-chlorinated stearic acid.

PMID- 8265521
TI  - Inhalation kinetics of C8 to C10 1-alkenes and iso-alkanes in the rat after
      repeated exposures.
AB  - The toxicokinetic properties of C8 and C10 1-alkenes and iso-alkanes have been
      investigated in rats during inhalation of 100 p.p.m. of the single hydrocarbons
      for 3 days, 12 hr/day. The concentration of hydrocarbon was measured in blood,
      brain, liver, kidneys and perirenal fat at days 1, 2 and 3, immediately after
      exposure and 12 hr after exposure on day 3. The 1-alkenes showed an efficient
      absorption to blood combined with extensive accumulation in organs, compared to
      the iso-alkanes. The concentration of 1-alkenes and iso-alkanes in blood, brain,
      liver and fat increased with increasing number of carbon atoms. The C9 and C10 1
      alkenes and iso-alkanes showed increasing concentration in fat during the
      exposure period and high concentrations 12 hr after cessation of exposure. The
      extensive accumulation in both blood and organs of 1-alkenes compared to any of
      the other groups of hydrocarbons may have a toxicologic relevance. Products which
      contain 1-alkenes should be handled carefully to minimize the risk of inhalation
      exposure.

PMID- 8265522
TI  - Identification of the gastrointestinal absorption site for cadmium chloride in
      vivo.
AB  - Most models for the study of the mechanism of intestinal absorption of Cadmium
      (Cd) have been using intestinal tissue in vitro or in situ. The in vivo
      experiments reported in this article were performed in an attempt to localize the
      site for gastrointestinal absorption of cadmium chloride during natural
      physiological conditions by oral exposure of mice to 109Cd-labelled CdCl2.
      Independent of exposure via drinking water or oral administration of a single
      dose, Cd was primarily deposited in the most proximal duodenum. Thus the present
      study as well as others indicate that absorption takes place in the proximal part
      of the intestine. Absorbed Cd is initially transported to the liver and deposited
      before being redistributed and accumulated in the kidneys. In this experimental
      model, dietary tetraethylthiuram disulfide exposure was shown to change the
      intestinal labelling profile and increase the whole-body retention as well as the
      intestinal deposition of Cd.

PMID- 8265523
TI  - Dose dependent transfer of 203lead to milk and tissue uptake in suckling
      offspring studied in rats and mice.
AB  - The dose-dependent transfer of 203Pb to milk and uptake in suckling rats and mice
      during a three-day nursing period was studied. On day 14 of lactation, the dams
      were administered a single intravenous dose of lead, labelled with 203Pb, in four
      or five doses from 0.0005 to 2.0 mg Pb/kg b.wt. There was a linear relationship
      between Pb levels in plasma and milk of both species. The Pb milk:plasma ratios
      at 24 hr after administration were 119 and 89 in mice and rats, respectively. At
      72 hr the Pb milk:plasma ratio had decreased to 72 in mice and 35 in rats. The
      tissue levels of lead in the suckling rats and mice were also linearly correlated
      with lead concentration in milk at 72 hr, showing that milk could be used as an
      indicator of lead exposure to the suckling offspring. It is concluded that lead
      is transported into rat and mouse milk to a very high extent and the excretion
      into milk is more efficient in mice than in rats. On the other hand, rat pups had
      higher lead levels in tissues than mice pups, which might be due to a higher
      bioavailability and/or a lower excretion of lead in rat pups. Thus, lead in
      breast milk could be used as a biological indicator of lead exposure in the
      mother as well as in the suckling offspring.

PMID- 8265524
TI  - Oral single doses of erythromycin and roxithromycin may increase the effects of
      midazolam on human performance.
AB  - Macrolide antibiotics are known to inhibit the metabolism of triazolam and
      midazolam in vitro and in vivo. To find out if significant interactions take
      place after single oral doses of these agents to man, 0.25 mg triazolam and 5, 10
      and 15 mg of midazolam in capsule from were given with and without 750 mg
      erythromycin or 300 mg roxithromycin to parallel groups of healthy subjects in
      four placebo-controlled double-blind studies. Objective tests and subjective
      assessments were made before the intake of hypnotics and 30 and 90 min after it.
      In Study I, triazolam impaired letter cancellation, the combination
      triazolam+erythromycin impaired digit symbol substitution and letter
      cancellation, and triazolam+roxithromycin impaired digit symbol substitution, all
      at 90 min. In Study II, midazolam 5 mg and midazolam 10 mg proved quite inert but
      the combination midazolam 5 mg+erythromycin impaired digit symbol substitution.
      In Study III, both midazolam 10 mg and midazolam 15 mg impaired digit
      substitution and letter cancellation, the effects of 15 mg being more prominent.
      The strongest drug effects were found with midazolam 10 mg+erythromycin which
      differed from placebo and midazolam (10 mg and 15 mg) in several objective and
      subjective test variables. In Study IV, the combination midazolam 10
      mg+roxithromycin impaired several objective and subjective variables but it was
      not stronger than midazolam 15 mg. These results were supported by the direct
      measurements of plasma midazolam in three subjects: erythromycin increased plasma
      midazolam more than roxithromycin and enhanced midazolam effects following the
      intake of midazolam 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265525
TI  - Guanidinoethanesulphonic acid facilitates retention of spatial memory in old
      rats.

PMID- 8265526
TI  - [Atheromatous aneurysm of the sub-renal aorta. Evolution of concepts for a
      current disease].

PMID- 8265527
TI  - [Desmoplastic tumors with multiple differentiation. A new entity. Six cases].
AB  - Desmoplastic tumours with divergent differentiation are principally located in
      the abdomen and develop locally or regionally. They occur in adolescents or young
      adults and are characterized at histology by a proliferation of undifferentiated
      small cells surrounded by a dense stroma. Only immuno-histo-chemistry provides
      the diagnosis. Since their chemosensitivity is rare and often partial the outcome
      is usually lethal. Six new cases of this recently described entity are presented
      here. The authors are in favour of a multidisciplinary and aggressive management,
      combining intensive polychemotherapy, extensive surgical exerisis and total
      abdominal radiotherapy.

PMID- 8265528
TI  - [Anonymous and free-of-charge centers for screening for HIV infection. Results of
      30 months of activity in Public Assistance in Paris hospitals].
AB  - The results of 30 months of activity of anonymous and free-of-charge HIV
      detection centres in Paris hospitals are presented. During this period (April
      1988 to December 1990), 15805 subjects were seen. This population accounts for
      about 11 percent of all French anonymous and free detection centres  in 1990, and
      for 26 percent of the number of subjects consulting in detection centres of the
      same type. Risk factors could be listed in 8132 consulting subjects: 73 percent
      were heterosexuals and not drug-addicts; 19.5 percent were homo- or bisexuals; 6
      percent were drug-addicts; 0.6 percent were both homosexuals and drug-addicts; 29
      percent of the 7806 persons questioned about their use of condoms stated that
      they used them often or always. A total of 15271 blood samples were taken. The
      percentage of seropositivity was 4.73 percent with a significant fall from 5.87
      percent in 1988 to 4.38 percent in 1990; 23.4 percent of homosexual drug-addicts,
      17.6 percent of heterosexual drug-addicts, 9.3 percent of homo- or bisexuals and
      1.3 percent of heterosexuals were seropositive. In the seropositive population,
      46.4 percent were homo- or bisexuals, 29.8 percent were drug-addicts, 19.7
      percent were heterosexuals and 3.7 percent were homosexual drug-addicts. Three
      subjects had been contaminated by blood transfusion. The percentage of
      seropositive subjects in our study was superior to the mean found in other
      anonymous and free detection centres (4.73 percent versus 3 percent in 1990),
      this probably reflecting the high prevalence of the infection in the Paris
      region. The seropositive subjects usually belonged to the categories primarily
      affected by the HIV. The percentage of seropositivity in our drug-addicts (17.6
      percent) was much lower than that usually reported in French drug-addicts (30 to
      40 percent).

PMID- 8265529
TI  - [Nosography of autism. Critical discussion of current classifications].
AB  - Child autism is a serious and early-forming developmental disorder and its
      nosography is evolving quickly. Classifications of autism have been produced
      since the works of Kanner in 1943 and especially in the last fifteen years, or so
      in order to respond to the needs of clinical practice and of research. Because of
      the presence of borderline or various uncommon clinical forms and, more
      generally, considering the heterogeneousness of clinical conditions concerning
      autism, it appears necessary to break up autism into better defined sub-groups.
      Moreover, the existing systems do not apply very well before the age of two or
      three, when the diagnosis and investigations nevertheless begin. Progress is
      achieved today by using simultaneously multidimensional and quantitative
      evaluations, an example of which is presented. In the future, a knowledge of
      etiological factors and/or the identification of biological markers will guide
      the classification of developmental disorders.

PMID- 8265531
TI  - [Early coronary atheroma. A little known complication of cerebrotendinous
      xanthomatosis].

PMID- 8265530
TI  - [Disorders of the bladder sphincter. Etiopathogenic approach].
AB  - Disorders of the vesico-sphincteral system are due to multiple causes
      (urological, gynaecological, neurological, psycho-behavioural, iatrogenic) which
      may be associated. By providing information on the type and evolution of these
      disorders and on the circumstances in which they developed, questioning is
      fundamental for the diagnosis. Completed by physical examination, it must precede
      all exploratory methods, including urodynamic, electrophysiological and
      radiological examinations. It allows these examinations to be graded and,
      compared with the results, it gives a better understanding of the physiopathology
      and aetiology of micturition disorders and therefore ensures their better
      treatment.

PMID- 8265532
TI  - [Hormone therapy for thyroid nodules: diagnostic and therapeutic value].

PMID- 8265533
TI  - [Relationship between lipoprotein (a) and vascular complications in diabetes
      mellitus].

PMID- 8265534
TI  - [Still's disease revealed by a retropharyngeal pseudo-abscess].

PMID- 8265535
TI  - [Age and sex; two new risk factors for hypersensitivity to latex].

PMID- 8265536
TI  - [History of "La Presse Medicale". 100 years in the life of a newspaper].

PMID- 8265537
TI  - [From ads to advertising].

PMID- 8265538
TI  - [Recovery of malignant hemopathies].

PMID- 8265539
TI  - [Past, present and future of organ transplantations].

PMID- 8265540
TI  - [From graft to histocompatibility].

PMID- 8265541
TI  - [History of lymphocytes].

PMID- 8265542
TI  - [Intensive care. Birth and development of a concept].

PMID- 8265543
TI  - [From humors to hormones. One hundred years that changed a world].

PMID- 8265544
TI  - [The century of microbiology].

PMID- 8265545
TI  - [Surgery 1893-1993].

PMID- 8265546
TI  - [From ears to eyes, or the revolutions of cardiology].

PMID- 8265547
TI  - [A look at semiology].

PMID- 8265548
TI  - [Lung cancer, disease of the century. Review of "La Presse Medicale" from 1893 to
      the present].

PMID- 8265549
TI  - [Smoking, one hundred years later].

PMID- 8265550
TI  - [Life and death of diseases].

PMID- 8265551
TI  - [Lhermitte's sign].

PMID- 8265552
TI  - [Albuminuria seen by Charles Talamon and nephrology at Tenon hospital].

PMID- 8265553
TI  - [Gastric chemistry one hundred years ago].

PMID- 8265554
TI  - [Simple ulcer of the duodenum. From 1894 to the present].

PMID- 8265555
TI  - [Toulouse-Lautrec's disease].

PMID- 8265556
TI  - [Charcot and the Daudet].

PMID- 8265557
TI  - [Doctor Rougon, therapist for degenerations].

PMID- 8265558
TI  - [Doctor Horace Bianchon, a physician's archetype].

PMID- 8265559
TI  - [Proust or an insomniac's word].

PMID- 8265560
TI  - Molecular basis of cooperativity in protein folding. IV. CORE: a general
      cooperative folding model.
AB  - The cooperative nature of the protein folding process is independent of the
      characteristic fold and the specific secondary structure attributes of a globular
      protein. A general folding/unfolding model should, therefore, be based upon
      structural features that transcend the peculiarities of alpha-helices, beta
      sheets, and other structural motifs found in proteins. The studies presented in
      this paper suggest that a single structural characteristic common to all globular
      proteins is essential for cooperative folding. The formation of a partly folded
      state from the native state results in the exposure to solvent of two distinct
      regions: (1) the portions of the protein that are unfolded; and (2) the
      "complementary surfaces," located in the regions of the protein that remain
      folded. The cooperative character of the folding/unfolding transition is
      determined largely by the energetics of exposing complementary surface regions to
      the solvent. By definition, complementary regions are present only in partly
      folded states; they are absent from the native and unfolded states. An
      unfavorable free energy lowers the probability of partly folded states and
      increases the cooperativity of the transition. In this paper we present a
      mathematical formulation of this behavior and develop a general cooperative
      folding/unfolding model, termed the "complementary region" (CORE) model. This
      model successfully reproduces the main properties of folding/unfolding
      transitions without limiting the number of partly folded states accessible to the
      protein, thereby permitting a systematic examination of the structural and
      solvent conditions under which intermediates become populated. It is shown that
      the CORE model predicts two-state folding/unfolding behavior, even though the two
      state character is not assumed in the model.

PMID- 8265561
TI  - Solution structure of tertiapin determined using nuclear magnetic resonance and
      distance geometry.
AB  - The solution structure of tertiapin, a 21-residue bee venom peptide, has been
      characterized by circular dichroism (CD), two-dimensional nuclear magnetic
      resonance (NMR) spectroscopy, and distance geometry. A total of 21 lowest error
      structures were obtained from distance geometry calculations. Superimposition of
      these structures shows that the backbone of tertiapin is very well defined. One
      type-I reverse turn from residue 4 to 7 and an alpha-helix from residue 12 to 19
      exist in the structure of tertiapin. The alpha-helical region is best defined
      from both conformational analysis and structural superimposition. The overall
      three-dimensional structure of tertiapin is highly compact resulting from side
      chain interactions. The structural information obtained from CD and NMR are
      compared for both tertiapin and apamin (ref. 3), another bee venom peptide.
      Tertiapin and apamin have some similar secondary structure, but display different
      tertiary structures.

PMID- 8265562
TI  - Structural relationships of homologous proteins as a fundamental principle in
      homology modeling.
AB  - Protein structure prediction is based mainly on the modeling of proteins by
      homology to known structures; this knowledge-based approach is the most promising
      method to date. Although it is used in the whole area of protein research, no
      general rules concerning the quality and applicability of concepts and procedures
      used in homology modeling have been put forward yet. Therefore, the main goal of
      the present work is to provide tools for the assessment of accuracy of modeling
      at a given level of sequence homology. A large set of known structures from
      different conformational and functional classes, but various degrees of homology
      was selected. Pairwise structure superpositions were performed. Starting with the
      definition of the structurally conserved regions and determination of
      topologically correct sequence alignments, we correlated geometrical properties
      with sequence homology (defined by the 250 PAM Dayhoff Matrix) and identity. It
      is shown that both the topological differences of the protein backbones and the
      relative positions of corresponding side chains diverge with decreasing sequence
      identity. Below 50% identity, the deviation in regions that are structurally not
      conserved continually increases, thus implying that with decreasing sequence
      identity modeling has to take into account more and more structurally diverging
      loop regions that are difficult to predict.

PMID- 8265563
TI  - Influence of protein flexibility on the redox potential of rubredoxin: energy
      minimization studies.
AB  - A theoretical investigation of the protein contribution to the redox potential of
      the iron-sulfur protein rubredoxin is presented. Structures of the oxidized and
      reduced forms of the protein were obtained by energy minimizing the oxidized
      crystal structure of Clostridium pasteurianum rubredoxin with appropriate charges
      and parameters. By including 102 crystal waters, structures close to the original
      crystal structure were obtained (rms difference of 1.16 A), even with extensive
      minimization, thus allowing accurate calculations of comparative energies. Our
      calculations indicate an energy change of about -60 kcal/mol (2.58 eV) in the
      protein alone upon reduction. This energy change was due to both the change in
      charge of the redox site and the subsequent relaxation of the protein. An energy
      minimization procedure for the relaxation gives rms differences between the
      oxidized and reduced states of about 0.2 A. The changes were small and occurred
      in both the backbone and sidechain mainly near the Fe-S center but contributed
      about -16 kcal/mol (0.69 eV) to the total protein contribution. Although the
      neglect of certain effects such as electronic polarization may make the
      relaxation energies calculated an upper limit, the results indicate that protein
      relaxation contributes substantially to the redox potential.

PMID- 8265564
TI  - Site specific point mutation changes specificity: a molecular modeling study by
      free energy simulations and enzyme kinetics of the thermodynamics in ribonuclease
      T1 substrate interactions.
AB  - We have theoretically and experimentally studied the binding of two different
      ligands to wild-type ribonuclease T1 (RNT1) and to a mutant of RNT1 with Glu-46
      replaced by Gln. The binding of the natural substrate 3'-GMP has been compared
      with the binding of a fluorescent probe, 2-aminopurine 3'-monophosphate (2AP),
      and relative free energies of binding of these ligands to the mutant and the wild
      type (wt) enzyme have been calculated by free energy perturbation methods. The
      free energy perturbations predict that the mutant RNT1-Gln-46 binds 2AP better
      than 3'GMP, in agreement with experiments on dinucleotides. Four free energy
      perturbations, forming a closed loop, have been performed to allow the detection
      of systematic errors in the simulation procedure. Because of the larger number of
      atoms involved, it was necessary to use a much longer simulation time for the
      change in the protein, i,e., the perturbation from Glu to Gln, than in the
      perturbation from 3'-GMP to 2AP. Finally the structure of the binding site is
      analyzed for understanding differences in catalytic speed and binding strength.

PMID- 8265565
TI  - Crystal structure of TGF-beta 2 refined at 1.8 A resolution.
AB  - The crystal structure of TGF-beta 2 has been refined using data collected with
      synchrotron radiation (CHESS) to 1.8 A resolution with a residual R (= sigma
      magnitude of Fo-magnitude of Fc/sigma magnitude of Fo) factor of 17.3%. The model
      consists of 890 protein atoms from all 112 residues and 59 water molecules. The
      monomer of TGF-beta 2 assumes a rather extended conformation and lacks a well
      defined hydrophobic core. Surface accessibility calculations show only 44% of the
      nonpolar surface is buried in the monomer. In contrast, 55.8% of the nonpolar
      surface area is buried when the two monomers form a dimer, a typical value for
      globular proteins. This includes a 1300 A2 buried interface area that is largely
      hydrophobic. Sequence comparisons using a profile derived from the refined TGF
      beta 2 structure suggest that the cluster of four disulfides (three
      intramonomeric disulfide bonds 15-78, 44-109, 48-111 forming a disulfide knot,
      and one intermonomeric disulfide 77-77) together with the extended beta strand
      region constitutes the conserved structural motif for the TGF-beta superfamily.
      This structural motif, without the 77-77 disulfide bond, defines also the common
      fold for a general family of growth factors, including the nerve growth factor
      and platelet-derived growth factor families. The fold is conserved only at the
      monomer level, while the active forms are dimers, suggesting that dimerization
      plays an important role in regulating the binding of these cytokines to their
      receptors and in modulating the biological responses.

PMID- 8265566
TI  - Molecular skins: a new concept for quantitative shape matching of a protein with
      its small molecule mimics.
AB  - A novel analytical method for comparing molecular shapes by optimizing the
      intersection of molecular "SKINS" has been developed. This method provides a
      quantitative measure of the shape similarity by maximizing the intersection
      volume of molecular surfaces with a finite thickness; a molecular skin. We report
      shape matching of a small tripeptide inhibitor (DFKi) of elastase class proteins
      with the 56 residue turkey ovomucoid inhibitor (TOMI). To match a large elastase
      inhibitor such as TOMI with a small inhibitor or drug, we found that it is
      necessary to use a skin match rather than molecular volume. Skin based
      comparisons of TOMI protein with DFKi successfully found the alignment expected
      from comparison of their respective crystallographic complexes with elastase
      (i.e. HLE/TOMI complex and PPE/tripeptide complex). In the skin comparison of the
      tripeptide with the TOMI protein, blind searching for skin matches involved
      optimization of the skin intersection from 172 starting positions randomly
      selected from a set of 500 points on the TOMI van der Waals surface [within 9.5 A
      of the Leu-18 on the TOMI binding loop (1 point/A2)]. The tripeptide center of
      mass was placed at these points and its orientation was randomized before
      optimization was initiated. The best skin intersection, 86.4 A3, was found three
      times and corresponds to the experimental alignment. The next best skin
      intersection was 78.1 A3 giving a discrimination factor in this case of 10%.
      Searches over the entire surface of the TOMI protein did not identify any new
      matches with skin intersection greater than 78.1 A3. Matching the DFKi with a
      TOMI structure relaxed from its crystal conformation by molecular dynamics gives
      similar results.

PMID- 8265567
TI  - Binding of cyanide, cyanate, and thiocyanate to human carbonic anhydrase II.
AB  - Computer simulation techniques are used to address the question of how cyanide
      and related ions interact with human carbonic anhydrase II (HCAII). Spectroscopic
      results have suggested that cyanide is coordinated with the zinc ion, while
      recent X-ray results suggest that the cyanide ion is noncovalently associated
      with the zinc-water or zinc-hydroxide form of the enzyme. We have carried out
      simulations on three models in an attempt to shed light on why the spectroscopic
      and X-ray results differ. The first model we studied (Model I) has cyanide
      directly coordinated to the zinc ion, the second has it noncovalently interacting
      with the zinc-hydroxide (high pH) form of the enzyme (Model II), and the third
      has cyanide noncovalently interacting with the zinc-water (low pH) form of the
      enzyme (Model III). None of these models is satisfactory in explaining the
      available structural data obtained from X-ray crystallography. This leads us to
      propose an alternative model, in which HCAII hydrates HCN to form an OH-/HCN
      complex coordinated to the Zn ion. Ab initio calculations are consistent with
      this model. Based on these results we are able to explain the observed
      crystallographic behavior of cyanate and, by inference, thiocyanate.

PMID- 8265568
TI  - Calculation of the pitch of the alpha-helical coiled coil: an addendum.

PMID- 8265569
TI  - Testosterone in egg yolks: an ornithologist's perspective.

PMID- 8265570
TI  - Cellular signaling: new insights into the action of the plant growth hormone
      auxin.

PMID- 8265571
TI  - Yolk is a source of maternal testosterone for developing birds.
AB  - The sex steroid hormones that affect development in birds have been thought to be
      produced exclusively by the embryo or neonate. I used radioimmunoassay to measure
      the amounts of androstenedione, 5 alpha-dihydrotestosterone, testosterone, 17
      beta-estradiol, and corticosterone in the yolk of freshly laid canary (Serinus
      canaria) and zebra finch (Poephila guttata) eggs. Testosterone was found in both
      canary and zebra finch eggs, but its contents were much higher in the former than
      in the latter. The testosterone content of canary eggs in a same clutch increased
      with the order of laying, regardless of the genetic sex of the offspring that
      hatched from these eggs. Yolk testosterone was also present in the eggs of female
      canaries that were kept without a male, indicating that it is of maternal origin.
      The social rank of juvenile canaries was positively correlated with the
      concentration of yolk testosterone in the eggs from which they hatched,
      suggesting that the development of aggressive behavior of offspring might be
      subject to modification by maternal testosterone. These findings indicate that
      female songbirds can bestow upon their eggs a dose of hormone that modifies the
      behavior of offspring. Variable doses of these hormones might explain some of the
      individual variation in offspring behavior.

PMID- 8265572
TI  - Importance of receptor occupancy, concentration differences, and ligand exchange
      in the insulin-like growth factor I receptor system.
AB  - We have investigated by use of placental membranes the mechanisms through which
      insulin-like growth factor I (IGF-I) comes to be associated with its alpha 2 beta
      2 receptor heterotetramer. Our results suggest that (i) at low ligand
      concentrations, the formation and disruption of IGF-I--receptor complexes are
      consistent with ligand binding de novo to empty receptors but not with equilibria
      involving ligand dissociation; (ii) at higher ligand concentrations, rapid
      exchange arising from the formation and collapse of bis-liganded receptors leads
      to a transiently perturbed receptor state; (iii) these nonclassical IGF-I
      receptor interactions depend on close communication between the alpha beta halves
      of the alpha 2 beta 2 holo-IGF-I receptor; and (iv) related processes based on
      ligand exchange have the potential for serving as biological sensors of changes
      in ligand concentration, while ordinary binding processes serve as sensors of
      ligand concentrations themselves. A model is presented in which one or two
      molecules of ligand can be bound to an alpha 2 beta 2 IGF-I receptor
      heterotetramer, new ligand becomes associated with receptor by exchanging for a
      previously bound molecule of IGF-I, and fluctuating changes in free-ligand
      concentration might lead to enhanced IGF-I function.

PMID- 8265573
TI  - Structurally engineered cytochromes with unusual ligand-binding properties:
      expression of Saccharomyces cerevisiae Met-80-->Ala iso-1-cytochrome c.
AB  - A strategy has been developed to express and purify a recombinant, nonfunctional
      axial-ligand mutant of iso-1-cytochrome c (Met-80-->Ala) in Saccharomyces
      cerevisiae in quantities necessary for extensive biophysical characterization. It
      involves coexpressing in the same plasmid (YEp213) the nonfunctional gene with a
      functional gene copy for complementation in a selective medium. The functional
      gene encodes a product with an engineered metal-chelating dihistidine site (His
      39 and Leu-58-->His) that enables efficient separation of the two isoforms by
      immobilized metal-affinity chromatography. The purified Met-80-->Ala protein
      possesses a binding site for dioxygen and other exogenous ligands. Absorption
      spectra of several derivatives of this mutant show striking similarities to those
      of corresponding derivatives of horseradish peroxidase, myoglobin, and cytochrome
      P450. The use of a dual-gene vector for cytochrome c expression together with
      metal-affinity separation opens the way for the engineering of variants with
      dramatically altered structural and catalytic properties.

PMID- 8265574
TI  - Strings of contiguous modified pentanucleotides with increased DNA-binding
      affinity can be used for DNA sequencing by primer walking.
AB  - Modified oligonucleotides containing 5-methylcytidine and/or 2-aminoadenosine
      form tighter hybrids with DNA and are, therefore, more efficient primers for DNA
      sequencing as compared to their natural counterparts. Strings of contiguous
      modified pentanucleotides can be used for DNA sequencing by primer walking.

PMID- 8265575
TI  - Transmembrane neural cell-adhesion molecule (NCAM), but not glycosyl
      phosphatidylinositol-anchored NCAM, down-regulates secretion of matrix
      metalloproteinases.
AB  - During embryogenesis interactions between cells and extracellular matrix play a
      central role in the modulation of cell motility, growth, and differentiation.
      Modulation of matrix structure is therefore crucial during development;
      extracellular matrix ligands, their receptors, extracellular proteinases, and
      proteinase inhibitors all participate in the construction, maintenance, and
      remodeling of extracellular matrix by cells. The neural cell-adhesion molecule
      (NCAM)-negative rat glioma cell line BT4Cn secretes substantial amounts of
      metalloproteinases, as compared with its NCAM-positive mother cell line BT4C. We
      have transfected the BT4Cn cell line with cDNAs encoding the human NCAM-B and -C
      isoforms. We report here that the expression of transmembrane NCAM-B, but not of
      glycosyl-phosphatidylinositol-linked NCAM-C, induces a down-regulation of 92-kDa
      gelatinase (matrix metalloproteinase 9) and interstitial collagenase (matrix
      metalloproteinase 1), indicating that cellular expression of the recognition
      molecule NCAM regulates the metabolism of the surrounding matrix.

PMID- 8265576
TI  - Effective immunization against cutaneous leishmaniasis with recombinant bacille
      Calmette-Guerin expressing the Leishmania surface proteinase gp63.
AB  - Leishmania parasites cause a spectrum of diseases that afflict the populations of
      86 countries in the world. The parasites can survive within the lysosomal
      compartments of the host's macrophages, unless those macrophages are
      appropriately activated. Despite the fact that protective immunity can be induced
      by vaccination with crude parasite preparations, little progress has been made
      toward a defined vaccine for humans. In this study the gene encoding the
      Leishmania surface proteinase gp63 was cloned and expressed as a cytoplasmic
      protein in a bacille Calmette-Guerin (BCG) vaccine strain. BALB/c and CBA/J mice
      were inoculated with a single dose of recombinant BCG and challenged with
      infective Leishmania major or Leishmania mexicana promastigotes. Significant
      protection was observed in both mouse strains against L. mexicana and in CBA/J
      against L. major, whereas only a delay in L. major growth was seen in BALB/c
      mice. Recombinant BCG also engendered a strong protective response against
      challenge with amastigotes of L. mexicana, demonstrating that the induced immune
      response recognized the intracellular form of the parasite. The results support
      the view that recombinant BCG expressing gp63 may prove a useful vaccine for
      inducing protective cell-mediated immune responses to Leishmania species causing
      American cutaneous leishmaniasis.

PMID- 8265577
TI  - DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun
      inoculations.
AB  - Plasmid DNAs expressing influenza virus hemagglutinin glycoproteins have been
      tested for their ability to raise protective immunity against lethal influenza
      challenges of the same subtype. In trials using two inoculations of from 50 to
      300 micrograms of purified DNA in saline, 67-95% of test mice and 25-63% of test
      chickens have been protected against a lethal influenza challenge. Parenteral
      routes of inoculation that achieved good protection included intramuscular and
      intravenous injections. Successful mucosal routes of vaccination included DNA
      drops administered to the nares or trachea. By far the most efficient DNA
      immunizations were achieved by using a gene gun to deliver DNA-coated gold beads
      to the epidermis. In mice, 95% protection was achieved by two immunizations with
      beads loaded with as little as 0.4 micrograms of DNA. The breadth of routes
      supporting successful DNA immunizations, coupled with the very small amounts of
      DNA required for gene-gun immunizations, highlight the potential of this
      remarkably simple technique for the development of subunit vaccines.

PMID- 8265578
TI  - The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic
      leucine zipper protein related to the v-maf oncogene.
AB  - Erythroid transcription factor NF-E2 is a tissue-restricted heterodimeric protein
      which recognizes an extended AP-1 motif [(T/C)TGCTGA(C/G)TCA(T/C)] found in the
      upstream locus control regions of the alpha- and beta-globin gene clusters. A
      cDNA clone encoding a cell-type-specific subunit of NF-E2, designated p45 NF-E2,
      has previously been characterized and shown to encode a basic-leucine zipper DNA
      binding protein. Here we describe protein purification and cloning of cDNA that
      encodes the second basic-leucine zipper subunit of the native NF-E2 heterodimer.
      This polypeptide, designated p18, is widely expressed. It displays extensive
      homology to the v-maf oncogene product and a human retinal-specific protein, NRL.
      Unusual features in the basic region shared by v-Maf, NRL, and p18 place them in
      a distinct subfamily of AP-1-like proteins.

PMID- 8265579
TI  - Modulation of K+ channels in Vicia stomatal guard cells by peptide homologs to
      the auxin-binding protein C terminus.
AB  - Transduction of the auxin stimulus in plants is thought to entail binding of the
      hormone to a soluble auxin-binding protein (ABP) outside the cell and subsequent
      interaction between this auxin-protein complex and an integral membrane receptor
      ("docking") protein that couples the signal across the plasma membrane. To
      explore the structural requirements for ABP function, synthetic peptides were
      prepared to the amino acid sequences of the predicted surface domains of ABPzm1,
      the dominant ABP from Zea. Biological function was assayed under voltage clamp,
      monitoring the ability of the peptides to evoke auxin-related modulations in
      inward- (IK,in) and outward-rectifying (IK,out) K+ channel activities of Vicia
      guard cells in the absence of added auxin. Only the peptide corresponding to the
      C-terminal domain of ABPzm1 was active. The dominant response was an inactivation
      of IK,in, although the peptide also evoked an activation of IK,out. Inactivation
      of IK,in was complete within 20-30 s and was fully reversible, was marked by a
      slowing of voltage-dependent activation and deactivation, and was dependent on
      peptide concentration (K1/2, 16 +/- 6 microM). Buffering cytoplasmic-free [Ca2+]
      with EGTA had no effect on IK,in response to the peptide. However, virtually
      complete and reversible block of the response was achieved when cytoplasmic pH
      (pHi) was brought under experimental control using the weak acid butyrate.
      Parallel measurements of pHi using the fluorescent dye 2',7'-bis(2-carboxyethyl
      5(6)-carboxyfluorescein (BCECF) and dual-wavelength laser-scanning confocal
      microscopy demonstrated that the C-terminal peptide evoked rapid and reversible
      cytoplasmic alkalinizations of 0.4 +/- 0.1 pHi unit and confirmed the antagonism
      of the pHi response in the presence of butyrate. These, and comparable results
      with the auxins indole acetic acid and 1-naphthyleneacetic acid, implicate the C
      terminal domain of ABPzm1 in auxin-ABP coupling to pHi and an associated
      intracellular signaling cascade.

PMID- 8265580
TI  - Quantitative determination of adenovirus-mediated gene delivery to rat cardiac
      myocytes in vitro and in vivo.
AB  - To optimize the use of modified adenoviruses as vectors for gene delivery to the
      myocardium, we have characterized infection of cultured fetal and adult rat
      cardiac myocytes in vitro and of adult cardiac myocytes in vivo by using a
      replication-defective adenovirus carrying the chloramphenicol acetyltransferase
      (CAT) reporter gene driven by the cytomegalovirus promoter (AdCMVCATgD). In
      vitro, virtually all fetal or adult cardiocytes express the CAT gene when
      infected with 1 plaque-forming unit of virus per cell. CAT enzymatic activity can
      be detected in these cells as early as 4 hr after infection, reaching near
      maximal levels at 48 hr. In fetal cells, CAT expression was maintained without a
      loss in activity for at least 1 week. Using in vitro studies as a guide, we
      introduced the AdCMVCATgD virus directly into adult rat myocardium and compared
      the expression results obtained from virus injection with those obtained by
      direct injection of pAdCMVCATgD plasmid DNA. The amount of CAT activity resulting
      from adenovirus infection of the myocardium was orders of magnitude higher than
      that seen from DNA injection and was proportional to the amount of input virus.
      Immunostaining for CAT protein in cardiac tissue sections following adenovirus
      injection demonstrated large numbers of positive cells, reaching nearly 100% of
      the myocytes in many regions of the heart. Expression of genes introduced by
      adenovirus peaked at 5 days but was still detectable 55 days following infection.
      Adenoviruses are therefore a very useful tool for high-efficiency gene transfer
      into the cardiovascular system.

PMID- 8265581
TI  - Induction of type I interferon genes and interferon-inducible genes in embryonal
      stem cells devoid of interferon regulatory factor 1.
AB  - Overexpression of interferon regulatory factor 1 (IRF-1) can induce expression of
      the interferon (IFN) beta gene, at least in certain cells. A role of IRF-1 in the
      activation of IFN-alpha genes has also been claimed. We have generated embryonal
      stem cells in which both IRF-1 alleles were disrupted. In undifferentiated
      embryonal stem cells, virus-induced levels of IFN-alpha RNA were similar for wild
      type and IRF-1%, and there was little induction of IFN-beta RNA in either cell
      type. In 8-day differentiated cells, the levels of virus-induced IFN-beta RNA,
      but not of IFN-alpha RNA, were about 10-fold higher than in undifferentiated
      cells and only slightly higher in wild-type than in IRF-1% cells. Thus, although
      IRF-1 at high levels may elicit or augment induction of IFN genes under certain
      circumstances, it is not essential for IFN gene induction by virus. Lack of IRF-1
      had no effect on the IFN-induced expression levels of the IFN-inducible genes
      tested; however, there was little or no constitutive expression of (2'
      5')oligoadenylate synthetase in IRF-1% embryonal stem cells, in contrast to wild
      type cells.

PMID- 8265582
TI  - Identification of human DNA topoisomerase I as a cofactor for activator-dependent
      transcription by RNA polymerase II.
AB  - The transcriptional activation of eukaryotic class II genes by sequence-specific
      regulatory proteins requires cofactors in addition to the general transcription
      factors. One cofactor (termed PC3) was purified from HeLa cells and identified by
      sequence analysis and functional assays as human DNA topoisomerase I
      (EC5.99.1.2). Under identical conditions PC3 mediates both a net activation of
      transcription by the acidic activator GAL4-AH and repression of basal
      transcription, thereby leading to a large induction of transcription by the
      activator. PC3-mediated activation of transcription is dependent on the presence
      of both the GAL4-AH activation domain and the TATA-binding protein (TBP)
      associated-factors (TAFs) in natural transcription factor TFIID, while repression
      of basal transcription is observed with either TFIID or the derived TBP alone.
      These results suggest novel functions, apparently through distinct mechanisms,
      for human DNA topoisomerase I in the regulation of transcription initiation by
      RNA polymerase II.

PMID- 8265583
TI  - The min K channel underlies the cardiac potassium current IKs and mediates
      species-specific responses to protein kinase C.
AB  - A clone encoding the guinea pig (gp) min K potassium channel was isolated and
      expressed in Xenopus oocytes. The currents, gpIsK, exhibit many of the
      electrophysiological and pharmacological properties characteristic of gpIKs, the
      slow component of the delayed rectifier potassium conductance in guinea pig
      cardiac myocytes. Depolarizing commands evoke outward potassium currents that
      activate slowly, with time constants on the order of seconds. The currents are
      blocked by the class III antiarrhythmic compound clofilium but not by the sotalol
      derivative E4031 or low concentrations of lanthanum. Like IKs in guinea pig
      myocytes, gpIsK is modulated by stimulation of protein kinase A and protein
      kinase C (PKC). In contrast to rat and mouse IsK, which are decreased upon
      stimulation of PKC, myocyte IK and gpIsK in oocytes are increased after PKC
      stimulation. Substitution of an asparagine residue at position 102 by serine
      (N102S), the residue found in the analogous position of the mouse and rat min K
      proteins, results in decreased gpIsK in response to PKC stimulation. These
      results support the hypothesis that the min K protein underlies the slow
      component of the delayed rectifier potassium current in ventricular myocytes and
      account for the species-specific responses to stimulation of PKC.

PMID- 8265584
TI  - Translation of the human LINE-1 element, L1Hs.
AB  - Full-length RNA transcribed from the human LINE-1 (L1) element L1 Homo sapiens
      (L1Hs) has a 900-nt, G+C-rich, 5'-untranslated region (UTR). The 5' UTR is
      followed by two long open reading frames, ORF1 and ORF2, which are separated from
      each other by an inter-ORF region of 33 nt that includes two or three in-frame
      stop codons. We examine here the mechanism(s) by which the translation of L1Hs
      ORF1 and ORF2 is initiated. A stable hairpin structure (delta G = -74.8
      kcal/mol), inserted at nt 661 of the 5' UTR, caused a 3- to 8-fold decrease in
      the in vitro and in vivo translation of either a lacZ reporter gene for ORF1 or
      the ORF1 polypeptide product, p40, but translation of a lacZ reporter gene in
      ORF2 was increased. The results are compatible with a model for ORF1 translation
      initiation in which the majority of ribosomes scan from a point 5' of nt 661 but
      suggest that ORF2 is not translated by attached ribosomes that reinitiate after
      the termination of ORF1 translation. Our data are compatible with a model whereby
      the translation of L1Hs ORF2 is initiated internally.

PMID- 8265585
TI  - Site-specific cleavage and joining of single-stranded DNA by VirD2 protein of
      Agrobacterium tumefaciens Ti plasmids: analogy to bacterial conjugation.
AB  - As an early stage of plant transformation by Agrobacterium tumefaciens, the Ti
      plasmid is nicked at the border sequences that delimit the T-DNA. Cleavage
      results in covalent attachment of VirD2 to the 5' terminal of the nicked strand
      by a process resembling initiation of DNA transfer that occurs in the donor cell
      during bacterial conjugation. We demonstrate that this cleavage can be reproduced
      in vitro: VirD2 protein, the border-cleaving enzyme, was overproduced and
      purified. Cleavage assays were performed with single-stranded
      oligodeoxyribonucleotides encompassing the Ti plasmid border region or the
      transfer origin's nick region of the conjugative plasmid RP4. VirD2 of pTiC58
      cleaves both border- and nick region-containing oligonucleotides. However, the
      relaxase TraI of RP4 can cut only the cognate nick regions. The respective
      proteins remain covalently bound to the 5' end of the cleavage sites, leaving the
      3' termini unmodified. VirD2-mediated oligonucleotide cleavage was demonstrated
      to be an equilibrium reaction that allows specific joining of cleavage products
      restoring border and nick regions, respectively. The possible role of VirD2 in T
      DNA integration into the plant cell's genome is discussed in terms of less
      stringent target-sequence requirements.

PMID- 8265586
TI  - Cloning of the large subunit of activator 1 (replication factor C) reveals
      homology with bacterial DNA ligases.
AB  - We have cloned a gene encoding a DNA-binding protein by Southwestern screening of
      a murine cDNA library with a double-stranded oligonucleotide containing the
      sequence from the bidirectional promoter of the alpha 1 and alpha 2 collagen IV
      genes. The middle portion of this 1131-amino acid protein has a region homologous
      to bacterial DNA ligases, and the more carboxyl portion contains several domains
      homologous to p40, p38, p37, and p36.5 subunits of activator 1 (A1, also called
      replication factor C), a human replication protein complex. Western blotting
      revealed that antiserum generated against part of the recombinant protein reacted
      specifically with the 145-kDa component of the purified human A1 complex,
      indicating that it is the murine counterpart of the A1 p145. Characterization of
      the DNA-binding activity of the recombinant fusion protein by gel mobility-shift
      assay revealed that it had a preference for a run of pyrimidines on one strand.
      Deletion analysis using recombinant proteins revealed that the DNA ligase-like
      domain was required for DNA-binding activity. The finding that the region
      required for the binding of murine A1 p145 to DNA has similarity to a domain
      found in DNA ligases suggests that this region may be utilized by both proteins
      in recognizing DNA.

PMID- 8265587
TI  - Hepatic gene therapy: efficient gene delivery and expression in primary
      hepatocytes utilizing a conjugated adenovirus-DNA complex.
AB  - Receptor-mediated endocytosis is an effective method for gene delivery into
      target cells. We have previously shown that DNA molecules complexed with
      asialoglycoprotein can be efficiently endocytosed by primary hepatocytes and the
      internalized DNA can be released from endosomes by the use of a replication
      defective adenovirus. Because the DNA and virus enter target cells independently,
      activity enhancement requires high concentrations of adenoviral particles. In
      this study, adenoviral particles were chemically conjugated to poly(L-lysine) and
      bound ionically to DNA molecules. Quantitative delivery to primary hepatocytes
      was achieved with significantly reduced viral titer when the asialoorosomucoid
      poly(L-lysine) conjugate was included in the complex. The conjugated adenovirus
      was used to deliver a DNA vector containing canine factor IX to mouse
      hepatocytes, resulting in the expression of significant concentrations of canine
      factor IX in the culture medium. The results suggest that receptor-mediated
      endocytosis coupled with an efficient endosomal lysis vector should permit the
      application of targeted and efficient gene delivery into the liver for gene
      therapy of hepatic deficiencies.

PMID- 8265588
TI  - The relationship between synthetic and editing functions of the active site of an
      aminoacyl-tRNA synthetase.
AB  - We have analyzed, by site-directed mutagenesis, the molecular basis of the
      editing function and its relation to the synthetic function of Escherichia coli
      methionyl-tRNA synthetase. The data obtained fit a model of the active site that
      partitions an amino acid substrate between synthetic and editing pathways.
      Hydrophobic and hydrogen bonding interactions direct the cognate substrate
      methionine through the synthetic pathway and prevent it from entering the editing
      pathway. Two hydrophobic interactions are proposed: between the side chain of Trp
      305 and a methyl group of methionine and between the benzene ring of Tyr-15 and
      the beta- and gamma-CH2 groups of the substrate. An essential hydrogen bond forms
      between the OH of Tyr-15 and an electron pair of the sulfur atom of methionine.
      Consistent with these functions, side chains of Trp-305 and Tyr-15 are localized
      on opposite sides of the cavity forming a putative methionine binding pocket that
      is observed in the three-dimensional crystallographic structure of methionyl-tRNA
      synthetase. Enzymes W305A, Y15A, and Y15F have diminished ability to discriminate
      against homocysteine in the synthetic reaction, compared to the wild-type enzyme.
      At the same time, mutant enzymes have lost the ability to discriminate against
      methionine in the editing reaction and edited Met-AMP to a similar extent as Hcy
      AMP. Interactions of residues Arg-233 and Asp-52 of methionyl-tRNA synthetase
      with the carboxyl and amino groups, respectively, of the substrate, which are
      essential for the synthetic function, were also essential for the editing
      function of the enzyme. Deacylation of Met-tRNA to S-methylhomocysteine
      thiolactone catalyzed by W305A, Y15A, and Y15F mutant enzymes was only slightly
      impaired relative to the wild-type enzyme. However, enzymes R233Q, R233A, and
      D52A did not deacylate Met-tRNA. The model also explains why the noncognate
      homocysteine is edited by methionyl-tRNA synthetase.

PMID- 8265589
TI  - Animals and fungi are each other's closest relatives: congruent evidence from
      multiple proteins.
AB  - Phylogenetic relationships among plants, animals, and fungi were examined by
      using sequences from 25 proteins. Four insertions/deletions were found that are
      shared by two of the three taxonomic groups in question, and all four are
      uniquely shared by animals and fungi relative to plants, protists, and bacteria.
      These include a 12-amino acid insertion in translation elongation factor 1 alpha
      and three small gaps in enolase. Maximum-parsimony trees were constructed from
      published data for four of the most broadly sequenced of the 25 proteins, actin,
      alpha-tubulin, beta-tubulin, and elongation factor 1 alpha, with the latter
      supplemented by three new outgroup sequences. All four proteins place animals and
      fungi together as a monophyletic group to the exclusion of plants and a broad
      diversity of protists. In all cases, bootstrap analyses show no support for
      either an animal-plant or fungal-plant clade. This congruence among multiple
      lines of evidence strongly suggests, in contrast to traditional and current
      classification, that animals and fungi are sister groups while plants constitute
      an independent evolutionary lineage.

PMID- 8265590
TI  - BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu
      element.
AB  - We demonstrate that the BC200 RNA gene, which encodes a neural small cytoplasmic
      RNA, is a member of the most prodigious family of interspersed repetitive DNA and
      that its product represents an example of a primate tissue-specific RNA
      polymerase III transcript. The BC200 RNA gene is an early monomeric member and
      one of the few postulated transcriptionally active Alu sequences in this family
      of nearly half a million retropositionally amplified elements dispersed
      throughout the human genome. Furthermore, the isolation of two pseudogenes, BC200
      beta and BC200 gamma, demonstrates the gene's transpositional ability.
      Interestingly, the BC200 beta pseudogene may have been generated by a conversion
      like event after the human/chimpanzee divergence, resulting in an exchange of the
      left arm of a dimeric Alu element with the BC200 RNA coding sequence. Our data on
      conserved features of the active BC200 alpha gene suggest that its RNA product
      has been "exapted" into a function of the primate brain and provides a selective
      advantage to the species.

PMID- 8265591
TI  - Transcriptional regulation of HLA-A and -B: differential binding of members of
      the Rel and IRF families of transcription factors.
AB  - HLA-A and -B transplantation antigens can be expressed differentially at the
      basal level and in response to interferons (IFNs). To determine which DNA control
      elements and nuclear factors are responsible for these differences, HLA-A and -B
      upstream regulatory regions were used in expression and mobility-shift analyses.
      The HLA-A enhancer was found to contain two Rel (KBF/NF-kappa B) binding motifs,
      while the HLA-B enhancer has only one and is transactivated less well by
      overexpression of the NF-kappa B p65 subunit. On the other hand, the HLA-B IFN
      response element mediates a much stronger induction by IFNs and has a higher
      affinity for IRF-1 and -2, which are transcription factors implicated in the
      regulation of major histocompatibility complex class I genes. These results
      suggest a molecular basis for the way in which HLA-A and -B loci have adapted to
      be differentially expressed and to respond to different sets of cytokine signals.

PMID- 8265592
TI  - Calcium permeability of the N-methyl-D-aspartate receptor channel in hippocampal
      neurons in culture.
AB  - We have developed a quantitative description for calcium permeability of the N
      methyl-D-aspartate receptor channel to permit predictions of the reversal
      potential and calcium influx at different voltages for different extracellular
      calcium concentrations. Increasing the external calcium concentration markedly
      shifted the reversal potential to positive values and simultaneously decreased
      the single-channel conductance at potentials negative to the reversal potential.
      Very simple quantitative descriptions of calcium permeation and channel block by
      calcium ions accurately characterize our data and permit the prediction of
      reversal potentials and magnitudes of calcium influx for a wide range of
      conditions.

PMID- 8265593
TI  - Synaptic inhibition regulates associative interactions between afferents during
      the induction of long-term potentiation and depression.
AB  - The induction of long-term potentiation and depression depends upon associative
      interactions between synapses that converge on individual dendrites. The distance
      over which these associative interactions occur is limited. The present study
      evaluates whether this limitation is regulated by synaptic inhibition. We
      evaluated the associative interactions between two inputs that terminate on
      different proximo-distal locations along the dendrites of dentate granule cells
      in the presence of the gamma-aminobutyric acid (GABA) antagonist bicuculline
      methiodide. Local blockade of GABAergic inhibition enhanced associative
      interactions between nonoverlapping inputs, compared to within-animal control
      sites, where inhibitory transmission was intact. The results suggest that
      synaptic inhibition limits interactions between excitatory synapses by creating
      current shunts that limit the spread of depolarization within the dendritic tree.

PMID- 8265594
TI  - DNA-binding properties and secondary structural model of the hepatocyte nuclear
      factor 3/fork head domain.
AB  - An 84-amino acid segment of QRF-1 [glutamine (Q)-rich factor 1], a newly cloned,
      B-cell-derived DNA-binding protein, shows significant sequence homology with the
      DNA-binding domains of the hepatocyte nuclear factor 3/fork head family of
      proteins. Here we demonstrate that this 84-amino acid domain is necessary and
      sufficient for DNA binding. We also propose a secondary structural model for the
      domain. At the N-terminal portion of the model, a basic hook structure is
      followed by two amphipathic helices separated by a turn. Invariant amino acid
      residues within the two proposed helices form the hydrophobic cores. An aromatic
      kink and a third amphipathic helix comprise the center of the domain. At the C
      terminus, two variable-length loops flank a putative 7-amino acid helix followed
      by a short basic region.

PMID- 8265595
TI  - Induction of erythroid-specific gene expression in lymphoid cells.
AB  - Erythropoietin (Epo) is a cytokine which specifically regulates differentiation
      and proliferation of erythroid progenitor cells. We report here that Epo receptor
      expressed in interleukin 3-dependent lymphoid Ba/F3 cells transmits both
      differentiation and growth signals. Epo stimulation of these cells leads to
      activation of transcription and/or translation of the erythroid-specific
      transcription factors GATA-1 and SCL, followed by the accumulation of both alpha-
      and beta-globin chains. These results suggest that expression and activation of
      the Epo receptor regulates erythroid-specific gene expression and might play a
      role in determining a cell lineage in vivo and that GATA-1 and SCL may exert
      their effects after Epo binds to its receptor. It was further found that chimeric
      receptors composed of extracellular domains of Epo receptor and cytoplasmic
      domains of interleukin 2 or interleukin 3 receptors could also induce erythroid
      specific gene expression in Ba/F3 cells. Taking these data together with previous
      observations, we conclude that interaction of the extracellular domains of the
      Epo receptor with other membrane components is essential for transmission of both
      the erythroid differentiation and the growth signals.

PMID- 8265596
TI  - Localization of the colchicine-binding site of tubulin.
AB  - We have previously shown that rat brain tubulin, a heterodimer consisting of an
      alpha and beta monomer, can be covalently labeled with [3H]colchicine by near UV
      irradiation. Most of the label appears in beta-tubulin. We show here that beta
      tubulin can be separated and purified from SDS preparative gels and analyzed by
      proteolysis. Chymotrypsin yielded a labeled approximately 4-kDa band that
      contained two peptides. Tryptic digestion also yielded an approximately 4-kDa
      band containing two peptides. Sequence analysis revealed a peptide of residues 1
      36 and 213-242 for chymotrypsin and a peptide of residues 1-46 and 214-241 for
      trypsin. To identify which peptide carried the label, limited hydrolysis of beta
      tubulin was done with trypsin; this procedure yielded a labeled 16-kDa N-terminal
      peptide and a 35-kDa C-terminal peptide, as identified by antibodies. Isolation
      of these peptides and extensive digestion with trypsin yielded two labeled
      peptides corresponding to residues 1-46 from the 16-kDa N-terminal fragment and
      residues 214-241 from the 35-kDa C-terminal fragment. These results show that at
      least two regions in beta-tubulin are specifically involved in colchicine binding
      and that the span of the colchicine molecule, < or = 11 A, bridges these two
      regions in the native beta monomer.

PMID- 8265597
TI  - Evolution of nuclear ribosomal RNAs in kinetoplastid protozoa: perspectives on
      the age and origins of parasitism.
AB  - Molecular evolutionary relationships within the protozoan order Kinetoplastida
      were deduced from comparisons of the nuclear small and large subunit ribosomal
      RNA (rRNA) gene sequences. These studies show that relationships among the
      trypanosomatid protozoans differ from those previously proposed from studies of
      organismal characteristics or mitochondrial rRNAs. The genera Leishmania,
      Endotrypanum, Leptomonas, and Crithidia form a closely related group, which shows
      progressively more distant relationships to Phytomonas and Blastocrithidia,
      Trypanosoma cruzi, and lastly Trypanosoma brucei. The rooting of the
      trypanosomatid tree was accomplished by using Bodo caudatus (family Bodonidae) as
      an outgroup, a status confirmed by molecular comparisons with other eukaryotes.
      The nuclear rRNA tree agrees well with data obtained from comparisons of other
      nuclear genes. Differences with the proposed mitochondrial rRNA tree probably
      reflect the lack of a suitable outgroup for this tree, as the topologies are
      otherwise similar. Small subunit rRNA divergences within the trypanosomatids are
      large, approaching those among plants and animals, which underscores the
      evolutionary antiquity of the group. Analysis of the distribution of different
      parasitic life-styles of these species in conjunction with a probable timing of
      evolutionary divergences suggests that vertebrate parasitism arose multiple times
      in the trypanosomatids.

PMID- 8265599
TI  - The mdm-2 gene is induced in response to UV light in a p53-dependent manner.
AB  - Irradiation of mammalian cells with UV light results in a dose-dependent
      accumulation of the p53 tumor-suppressor gene product that is evident within 2
      hr. UV treatment causes a dramatic increase in p53-specific transcriptional
      transactivation activity and an increase in expression of the p53-responsive gene
      mdm-2. UV-stimulated mdm-2 expression is not directly correlated with the level
      of p53 protein in a cell because mdm-2 induction is delayed at high UV doses even
      though p53 levels rise almost immediately. Cells lacking p53 protein do not
      respond to UV by increasing their expression of mdm-2. The delayed induction of
      mdm-2 at high UV doses suggests that, in addition to p53 protein levels, other
      factors contribute to the regulation of mdm-2 expression following UV treatment.
      The time of induction of mdm-2 in cells treated with UV light correlates with
      recovery of normal rates of DNA synthesis, presumably after DNA repair. These
      data indicate a possible role for mdm-2 in cell cycle progression.

PMID- 8265598
TI  - Osteoporosis induced in mice by overproduction of interleukin 4.
AB  - Osteoporosis is a common disease in which loss of bone mass results in skeletal
      fragility. The development of therapies for this disorder has been hampered by
      the lack of a convenient animal model. Here we describe a disorder in bone
      homeostasis in transgenic mice that inappropriately express the cytokine
      interleukin 4 (IL-4) under the direction of the lymphocyte-specific proximal
      promoter for the lck gene. Bone disease in lck-IL-4 mice appeared to result from
      markedly decreased bone formation by osteoblasts, features strikingly similar to
      those observed in cases of severe low-turnover human involutional osteoporosis.
      By 2 months of age, female and male lck-IL-4 mice invariably developed severe
      osteoporosis of both cortical and trabecular bone. Osteoporosis was observed in
      two independently derived founder animals, indicating that this phenotype was
      directly mediated by the IL-4 transgene.

PMID- 8265600
TI  - Rapid solution assays for retroviral integration reactions and their use in
      kinetic analyses of wild-type and mutant Rous sarcoma virus integrases.
AB  - A rapid method for quantitating products of the oligodeoxynucleotide processing
      reaction in vitro has been developed to facilitate enzymatic studies of the
      retroviral integrases. Unlike earlier procedures, this assay does not depend on
      polyacrylamide gel electrphoresis but separates products by batch adsorption to
      PEI-cellulose. A joining assay has also been modified, to facilitate measurement
      of the two distinct steps in the integration reaction under parallel conditions.
      Since these methods allow quantitation of numerous samples in a short period of
      time, they are especially useful for investigation of kinetic parameters and to
      measure the effects of possible inhibitors of integrase. These assay systems were
      used to examine the enzymatic activity of wild-type Rous sarcoma virus integrase
      and selected mutant proteins with substitutions of single conserved amino acids.
      In contrast to previous studies, reactions were performed under conditions of
      substrate excess, and rates, rather than yields of product generated after a
      given period of incubation, were determined. The results showed that
      substitutions of several highly conserved residues in what is most likely an
      evolutionarily conserved catalytic domain of the integrases resulted in a 4- to
      10-fold decrease in the apparent rate of processing relative to wild type, under
      optimized standard conditions. Changing an invariant acidic residue reduced the
      rate by approximately 60-fold. When joining activity was determined, the relative
      effects of the substitutions tested generally paralleled the results with
      processing. However, with both wild-type and mutant integrase proteins, the
      linear phase of the joining reaction was preceded by what appears to be an
      exponential "burst" phase.

PMID- 8265601
TI  - Catalytic contribution of flap-substrate hydrogen bonds in "HIV-1 protease"
      explored by chemical synthesis.
AB  - An analogue of "HIV-1 protease" was designed in which the ability to donate
      important water-mediated hydrogen bonds to substrate was precisely and directly
      deleted. Chemical ligation of unprotected peptide segments was used to synthesize
      this "backbone-engineered" enzyme. The functionally relevant amide -CONH- linkage
      between residues Gly49-Ile50 in each flap of the enzyme was replaced by an
      isosteric thioester -COS- bond. The backbone-engineered enzyme had normal
      substrate specificity and affinity (Km). However, the catalytic activity (kcat)
      was reduced approximately 3000-fold compared to the native amide bond-containing
      enzyme. Inhibition by the reduced peptide bond substrate analogue MVT-101 was
      unaffected compared with native enzyme. By contrast, the normally tight-binding
      hydroxyethylamine inhibitor JG-365 bound to the backbone-engineered enzyme with
      an approximately 2500-fold reduction in affinity. The reduced catalytic activity
      of the -Gly49-psi(COS)-Ile50-backbone-engineered enzyme analogue provides direct
      experimental evidence to support the suggestion that backbone hydrogen bonds from
      the enzyme flaps to the substrate are important for the catalytic function of the
      HIV-1 protease.

PMID- 8265602
TI  - Val-->Ala mutations selectively alter helix-helix packing in the transmembrane
      segment of phage M13 coat protein.
AB  - Val-->Ala mutations within the effective transmembrane segment of a model single
      spanning membrane protein, the 50-residue major coat (gene VIII) protein of
      bacteriophage M13, are shown to have sequence-dependent impacts on stabilization
      of membrane-embedded helical dimeric structures. Randomized mutagenesis performed
      on the coat protein hydrophobic segment 21-39 (YIGYAWAMV-VVIVGATIGI) produced a
      library of viable mutants which included those in which each of the four valine
      residues was replaced by an alanine residue. Significant variations found among
      these Val-->Ala mutants in the relative populations and thermal stabilities of
      monomeric and dimeric helical species observed on SDS/PAGE, and in the range of
      their alpha-helix-->beta-sheet transition temperatures confirmed that
      intramembranous valine residues are not simply universal contributors to membrane
      anchoring. Additional analyses of (i) nonmutatable sites in the mutant protein
      library, (ii) the properties of the double mutant V29A-V31A obtained by recycling
      mutant V31A DNA through mutagenesis procedures, and (iii) energy-minimized
      helical dimer structures of wild-type and mutant V31A transmembrane regions
      indicated that the transmembrane hydrophobic core helix of the M13 coat protein
      can be partitioned into alternating pairs of potential protein-interactive
      residues (V30, V31; G34, A35; G38, I39) and membrane-interactive residues (M28,
      V29; I32, V33; T36, I37). The overall results consitute an experimental approach
      to categorizing the distinctive contributions to structure of the residues
      comprising a protein-protein packing interface vs. those facing lipid and confirm
      the sequence-dependent capacity of specific residues within the transmembrane
      domain to modulate protein-protein interactions which underlie regulatory events
      in membrane proteins.

PMID- 8265603
TI  - Kinesin swivels to permit microtubule movement in any direction.
AB  - Kinesin is a motor protein that uses the energy derived from ATP hydrolysis to
      transport organelles along microtubules. By analyzing the thermal fluctuation of
      microtubules tethered to glass surfaces by single molecules of kinesin, we have
      measured the torsional flexibility of the motor protein. The torsional stiffness
      of kinesin, (117 +/- 19) x 10(-24) N.m.rad-1 (mean +/- SEM), is so low that one
      kT of energy (approximately 4.1 x 10(-21) J at room temperature) is sufficient to
      twist a kinesin molecule through more than 360 degrees from its resting
      orientation. Consistent with this flexibility, motility assays show that one or
      more kinesin molecules can move a microtubule equally well in any direction.
      These results explain how a motor on the surface of an organelle can rapidly bind
      to and capture a microtubule irrespective of the organelle's orientation.
      Furthermore, the flexibility ensures that several motors can efficiently work
      together even though they are randomly oriented on the surface of an organelle
      rather than being in precise arrays like the motors of muscle and cilia.

PMID- 8265604
TI  - Evidence that facilitative glucose transporters may fold as beta-barrels.
AB  - A widely accepted model for the structure of the facilitative glucose
      transporters (GLUTs) predicts that they form 12 transmembrane alpha-helices and
      that the highly conserved sequence Ile-386-Ala-405 in GLUT1 is intracellular. We
      raised a polyclonal antibody against a synthetic peptide encompassing this
      conserved sequence and found that antibody treatment increased 2-deoxy-D-glucose
      (DOG) uptake in Xe-nopus oocytes expressing GLUT1, GLUT2, or GLUT4 only when
      applied to the extracellular side. This effect was dose dependent and was
      specifically blocked by competition with the peptide Ile-386-Ala-405; it was due
      to a decrease in the Km for the transport of DOG. To ascertain GLUT orientation,
      we raised anti-peptide antibodies against the last 21 and 25 C-terminal amino
      acids of GLUT1 and GLUT4, respectively, which were previously shown to be
      intracellular. These antibodies increased DOG uptake when injected into oocytes
      expressing GLUT1 and GLUT4, but not when added extracellularly. Prompted by the
      noted discrepancy, we found sequence similarity between GLUTs and porins, two of
      which are known from crystallography to form 16-stranded transmembrane
      antiparallel beta-barrels. Analysis of the hydrophobicity, amphiphilicity, and
      turn propensity of GLUT1 leads us to propose that GLUTs fold as porin-like
      transmembrane beta-barrels. This model is consistent with the results of the
      present antibody studies and also with previously published experimental evidence
      inconsistent with the 12-helix model.

PMID- 8265605
TI  - Cellular and subcellular immunolocalization of vasopressin-regulated water
      channel in rat kidney.
AB  - Vasopressin (antidiuretic hormone) regulates body water balance by controlling
      water permeability of the renal collecting ducts. The control mechanisms may
      involve alterations in the number or unit conductance of water channels in the
      apical plasma membrane of collecting-duct cells. How this occurs is unknown, but
      indirect evidence exists for the "shuttle" hypothesis, which states that
      vasopressin causes exocytic insertion of water channel-laden vesicles from the
      apical cytosol. To test key aspects of the shuttle hypothesis, we have prepared
      polyclonal antisera against the recently cloned collecting-duct water channel
      protein and used the antisera in immunolocalization studies (light and electron
      microscopic levels) in thin and ultrathin cryosections from rat kidney. Labeling
      was seen exclusively in collecting-duct principal cells and inner medullary
      collecting-duct cells. Apical membrane labeling was intense. There was heavy
      labeling of abundant small subapical vesicles and of membrane structures within
      multivesicular bodies. In addition, labeling of basolateral plasma membranes in
      inner medullary collecting ducts was present. Depriving rats of water for 24 or
      48 hr markedly increased collecting-duct water-channel protein expression
      determined by immunoblotting and immunolabeling. These results are compatible
      with at least two complementary modes of water-channel regulation in collecting
      duct cells: (i) control of channel distribution between the apical membrane and a
      reservoir in subapical vesicles (shuttle hypothesis) and (ii) regulation of the
      absolute level of expression of water-channel protein.

PMID- 8265606
TI  - A fourth class of theta-replicating plasmids: the pAM beta 1 family from gram
      positive bacteria.
AB  - Plasmid pAM beta 1 from Enterococcus faecalis uses a unidirectional theta mode of
      replication. We show here that this replication (i) is dependent on a plasmid
      encoded replication protein (Rep) but not on a DNA structure typical for origins
      of most Rep-dependent plasmids and (ii) is initiated by DNA polymerase I (PolI).
      pAM beta 1 minimal replicon shares no homology with highly conserved ColE1-type
      replicons, which use PolI for initiation but do not encode a Rep, or with ColE2
      and ColE3 replicons, which require PolI for replication and encode a Rep. We
      propose that pAM beta 1 and a number of other naturally occurring and closely
      related plasmids from a distinct plasmid class.

PMID- 8265607
TI  - Molecular basis of aromatase deficiency in an adult female with sexual
      infantilism and polycystic ovaries.
AB  - We identified two mutations in the CYP19 gene responsible for aromatase
      deficiency in an 18-year-old 46,XX female with ambiguous external genitalia at
      birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The
      coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from
      genomic DNA and sequenced directly. Direct sequencing of the amplified DNA from
      the patient revealed two single-base changes, at bp 1303 (C-->T) and bp 1310 (G-
      >A) in exon X, which were newly found missense mutations and resulted in codon
      changes of R435C and C437Y, respectively. Subcloning followed by sequencing
      confirmed that the patient is a compound heterozygote. The results of restriction
      fragment length polymorphism analysis and direct sequencing of the amplified exon
      X DNA from the patient's mother indicate maternal inheritance of the R435C
      mutation. Transient expression experiments showed that the R435C mutant protein
      had approximately 1.1% of the activity of the wild type, whereas C437Y was
      totally inactive. Cysteine-437 is the conserved cysteine in the heme-binding
      region believed to serve as the fifth coordinating ligand of the heme iron. To
      our knowledge, this patient is the first adult to have described the cardinal
      features of a syndrome of aromatase deficiency. Recognition that such defects
      exist will lead to a better understanding of the role of this enzyme in human
      development and disease.

PMID- 8265608
TI  - Enhancer activity of light-responsive regulatory elements in the untranslated
      leader regions of cyanobacterial psbA genes.
AB  - Three psbA genes encoding the D1 protein of the photosystem II reaction center
      are differentially expressed under different light intensities in the
      cyanobacterium Synechococcus sp. strain PCC 7942. Two of the three psbA genes,
      psbAII and psbAIII, are induced rapidly when light intensity is increased from
      125 x 10(-6) mol.m-2.s-1 to 750 x 10(-6) mol.m-2.s-1. A recombinational cloning
      vector that carries a transcriptional lacZ reporter gene was used to characterize
      the controlling elements responsible for light induction. At least three distinct
      cis elements are present in the regulatory regions of pbsAII and psbAIII: basal
      promoters, comparable to Escherichia coli sigma 70 promoters in position and
      sequence, confer constitutive expression of the genes under both low and high
      light intensities; negative elements upstream of the promoters down-regulate the
      expression of the corresponding gene; and sequences downstream of the promoters
      that correspond to the untranslated leader regions of the mRNAs (+1 to +41 in
      psbAII and +1 to +39 in psbAIII) are responsible for increased expression under
      high light. When these light-responsive elements were combined with an E. coli
      promoter (conII) in different positions and orientations, the expression of the
      lacZ gene was induced 4- to 11-fold. The induction of gene expression under high
      light by these enhancers was position independent but orientation dependent. When
      the elements were combined with the conII promoter in the correct orientation,
      they also conferred a small but reproducible level of light-responsive expression
      on this E. coli promoter.

PMID- 8265609
TI  - Active immunity against the CD4 receptor by using an antibody antigenized with
      residues 41-55 of the first extracellular domain.
AB  - Using the process of "antibody antigenization," we engineered two antibody
      molecules carrying in the third complementarity-determining region of the heavy
      chain variable domain a 7-mer or a 15-mer peptide epitope of the first
      extracellular domain (D1) of human CD4 receptor--namely, Ser-Phe-Leu-Thr-Lys-Gly
      Pro-Ser (SFLTKGPS; positions 42 through 49) and Gly-Ser-Phe-Leu-Thr-Lys-Gly-Pro
      Ser-Lys-Leu-Asn-Asp-Arg-Ala (GSFLTKGPSKLNDRA; positions 41 through 55). These
      amino acid sequences are contained in the consensus binding site for the human
      immunodeficiency virus (HIV) on CD4 receptor. Both antigenized antibodies (AgAbs)
      bound recombinant gp120 and were recognized by a prototype monoclonal antibody to
      CD4 whose binding site is within amino acid residues 41-55. AgAbs were then used
      as immunogens in rabbits and mice to elicit a humoral response against CD4. Only
      the AgAb carrying the sequence 41GSFLTKGPSKLN-DRA55 induced a response against
      CD4. The induced antibodies showed specificity for the amino acid sequence of CD4
      engineered in the AgAb molecule, were able to inhibit the formation of syncytia
      between human CD4+ T cells MOLT-3 and 8E5 (T cells that are constitutively
      infected with HIV), and stained human CD4+ CEM T cells. Four murine monoclonal
      antibodies were used to analyze the relationship between syncytia inhibition and
      CD4 binding at the single antibody level, and indicated that recognition of
      native CD4 is not an absolute requirement for inhibition of syncytia. This study
      demonstrates that antigenized antibodies can be used as immunogens to elicit site
      specific and biologically active immunity to CD4. The importance of this approach
      as a general way to induce anti-receptor immunity and as a possible new measure
      to immunointervention in HIV infection is discussed.

PMID- 8265610
TI  - Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive
      and inducible cyclooxygenase.
AB  - Constitutive cyclooxygenase (COX-1; prostaglandin-endoperoxide synthase, EC
      1.14.99.1) is present in cells under physiological conditions, whereas COX-2 is
      induced by some cytokines, mitogens, and endotoxin presumably in pathological
      conditions, such as inflammation. Therefore, we have assessed the relative
      inhibitory effects of some nonsteroidal antiinflammatory drugs on the activities
      of COX-1 (in bovine aortic endothelial cells) and COX-2 (in endotoxin-activated
      J774.2 macrophages) in intact cells, broken cells, and purified enzyme
      preparations (COX-1 in sheep seminal vesicles; COX-2 in sheep placenta). Similar
      potencies of aspirin, indomethacin, and ibuprofen against the broken cell and
      purified enzyme preparations indicated no influence of species. Aspirin,
      indomethacin, and ibuprofen were more potent inhibitors of COX-1 than COX-2 in
      all models used. The relative potencies of aspirin and indomethacin varied only
      slightly between models, although the IC50 values were different. Ibuprofen was
      more potent as an inhibitor of COX-2 in intact cells than in either broken cells
      or purified enzymes. Sodium salicylate was a weak inhibitor of both COX isoforms
      in intact cells and was inactive against COX in either broken cells or purified
      enzyme preparations. Diclofenac, BW 755C, acetaminophen, and naproxen were
      approximately equipotent inhibitors of COX-1 and COX-2 in intact cells. BF 389,
      an experimental drug currently being tested in humans, was the most potent and
      most selective inhibitor of COX-2 in intact cells. Thus, there are clear
      pharmacological differences between the two enzymes. The use of such models of
      COX-1 and COX-2 activity will lead to the identification of selective inhibitors
      of COX-2 with presumably less side effects than present therapies. Some
      inhibitors had higher activity in intact cells than against purified enzymes,
      suggesting that pure enzyme preparations may not be predictive of therapeutic
      action.

PMID- 8265611
TI  - Pulse mass measles vaccination across age cohorts.
AB  - Although vaccines against measles have been routinely applied over a quarter of a
      century, measles is still persistent in Israel, with major epidemics roughly
      every 5 years. Recent serological analyses have shown that only 85% of Israelis
      aged 18 years have anti-measles IgG antibodies. Considering the high
      transmissibility of the virus and the high level of herd immunity required for
      disease eradication, the Israeli vaccination policy against measles is now being
      reevaluated. Motivated by theoretical studies of populations in perturbed
      environments, we examined the possibility of replacing the conventional cohort
      vaccination strategy by a pulse strategy--i.e., periodic vaccination of several
      age cohorts at the same time. Numerical studies of a deterministic age-structured
      model suggest that vaccination, which renders immunity to no more than 85% of the
      susceptible children aged 1-7 years, once every 5 years will suffice to prevent
      epidemics in Israel, where infection rate is highest amongst schoolchildren. The
      model suggests that by using such a strategy the density of susceptible
      individuals is always kept below the threshold above which recurrent epidemics
      will be maintained. Analysis of simpler, non-age-structured, models serves to
      clarify the basic properties of the proposed strategy. Our theoretical results
      indicate that the advantages and disadvantages of a pulse strategy should be
      seriously examined in Israel and in countries with similar patterns of measles
      virus transmission.

PMID- 8265612
TI  - Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate
      reductase-thymidylate synthase marker based on drug-resistance mutations in
      malaria.
AB  - To facilitate genetic analysis of the protozoan parasite Toxoplasma gondii,
      sequences derived from the parasite's fused dihydrofolate reductase-thymidylate
      synthase (DHFR-TS) gene have been used to produce vectors suitable for stable
      molecular transformation. Mutations introduced into the DHFR coding region by
      analogy with pyrimethamine-resistant malaria confer drug resistance to
      Toxoplasma, providing useful information on the structure of fused DHFR-TS
      enzymes and a powerful selectable marker for molecular genetic studies. Depending
      on the particular drug-resistance allele employed and the conditions of
      selection, stable resistance can be generated either by single copy nonhomologous
      insertion into chromosomal DNA or by massively amplified transgenes. Frequencies
      of integration are independent of selection, and transgenes are stable without
      continued selection. Cointegration of a reporter gene adjacent to the selectable
      marker (under the control of an independent promoter) shows no loss of the
      cointegrated sequences over many parasite generations. By bringing the full power
      of molecular genetic analysis to bear on Toxoplasma, these studies should greatly
      facilitate the development of a model genetic system for Apicomplexan parasites.

PMID- 8265613
TI  - Discovery of biologically active peptides in random libraries: solution-phase
      testing after staged orthogonal release from resin beads.
AB  - To speed drug discovery, we developed an approach for identification of
      individual peptides with a desired biological activity from a library containing
      millions of peptides. The approach uses sequential orthogonal release of
      chemically synthesized peptides from insoluble beads, followed by testing in
      solution. In this system, each bead within a library of beads has one peptide
      sequence, but peptide molecules are attached to the bead with three types of
      chemical linkers, including two linkers cleavable at different pH optima. An
      uncleavable linker keeps some peptide attached to the bead for sequencing
      positives from the solution assay. Applicability of this discovery technique was
      documented by identifying ligands for a monoclonal antibody and for the human
      platelet fibrinogen receptor, glycoprotein IIb/IIIa.

PMID- 8265614
TI  - Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated
      cells.
AB  - Nck, an oncogenic protein composed of one SH2 and three SH3 domains, is a common
      target for various cell surface receptors. Nck is thought to function as an
      adaptor protein to couple cell surface receptors to downstream effector molecules
      that regulate cellular responses induced by receptor activation. In this report,
      we show that Nck forms a stable complex in vivo with IRS-1 in insulin-stimulated
      cells. The interaction between IRS-1 and Nck is mediated by the binding of the
      SH2 domain of Nck to tyrosine-phosphorylated IRS-1. Although Nck associates with
      IRS-1, Nck phosphorylation is not affected by insulin stimulation. Furthermore,
      in vitro and in vivo studies show that the SH2 domains of Nck, GRB2, and p85 bind
      distinct phosphotyrosine residues in IRS-1. After insulin stimulation all three
      signaling molecules can be found complexed to a single IRS-1 molecule. These
      findings provide further evidence that, in response to insulin stimulation, IRS-1
      acts as an SH2 docking protein that coordinates the regulation of various
      different signaling pathways activated by the insulin receptor.

PMID- 8265615
TI  - Age-dependent appearance of non-major histocompatibility complex-restricted
      helper T cells.
AB  - T cells which recognize antigen in association with self major histocompatibility
      complex (MHC) molecules are positively selected within the thymus. This results
      in skewing of the T-cell repertoire toward the recognition of antigenic peptides
      presented by self MHC molecules. While the thymus gland involutes at a relatively
      young age, bone marrow function and the size of the peripheral T-cell pool are
      maintained with age. We have investigated the MHC restriction of helper T-cell
      function for B-cell production of specific antibody in mice of different ages.
      Splenic helper T cells from 2- to 3-month old mice immunized with phosphocholine
      keyhole limpet hemocyanin conjugate were MHC-restricted as defined by their
      capacity to induce phosphocholine-specific antibody synthesis by syngeneic but
      not by allogeneic B cells. In contrast, splenic T cells from immunized 18- to 20
      month-old mice induced specific anti-phosphocholine antibodies by both syngeneic
      and allogeneic B cells. No evidence of polyclonal immunoglobulin synthesis was
      detected. The ability of T cells from old mice immunized with phosphocholine
      keyhole limpet hemocyanin to induce phosphocholine-specific antibody synthesis by
      B cells from allogeneic mice was inhibited by T cells from immunized young mice.
      These findings suggest that non-MHC-restricted T-cell helper activity in old mice
      results from the loss of T cells, present in young mice, which suppress non-MHC
      restricted helper cells.

PMID- 8265616
TI  - Multiple motifs regulate the B-cell-specific promoter of the B29 gene.
AB  - The B-cell-specific B29 and mb1 genes code for covalently linked proteins (B29 or
      Ig beta and mb1 or Ig alpha, respectively) associated with membrane
      immunoglobulins in the antigen receptor complex on B cells. We have functionally
      analyzed the upstream region of the B29 gene and have identified a 164-bp region
      which comprises the minimal promoter responsible for B-cell-specific
      transcription. Linker scanning mutagenesis of this minimal promoter has
      established that both the previously identified octamer motif and a DNA motif
      that binds an unknown protein factor are critical for B29 gene expression in a
      pre-B-cell and B-cell line. Further mutations showed that binding motifs for Ets,
      microB/LyF1, and Sp1 also significantly contributed to the overall activity of
      the minimal B29 promoter. However, the relative contribution of certain motifs to
      promoter activity was different in a pre-B versus a B-cell line. The microB/LyF1
      motif was necessary for full promoter activity in the pre-B cells but was not
      required in the B cells.

PMID- 8265617
TI  - Mevalonate availability and cardiovascular functions.
AB  - Data delineating the relationship between disorders of cholesterol metabolism and
      elevated blood pressure (BP) do not exist. We postulated that mevalonate, the
      metabolic precursor of endogenous cholesterol and the direct product of 3-hydroxy
      3-methylglutaryl-CoA reductase, was a contributing factor for the maintenance of
      vascular tone and systemic BP. We conducted in vivo, ex vivo, and in vitro
      experiments in normotensive and hypertensive rats, where exogenous mevalonate and
      lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase,
      were used, respectively, to increase or limit mevalonate availability. Mevalonate
      decreased BP in the whole animal without significant change in plasma
      cholesterol. Incubation of aortas with mevalonate attenuated their reactivity to
      norepinephrine and increased their response to endothelium-dependent and 
      independent relaxing factors. Lovastatin, in contrast, had the opposite effect in
      vivo and in vitro: it increased BP, enhanced vascular response to norepinephrine,
      and impaired endothelium-dependent and -independent relaxations. Neither agent
      modified cholesterol vascular content. Alteration of vascular reactivity was also
      observed in resistance vessels from animals pretreated with lovastatin. Our
      findings suggest that mevalonate availability is an unrecognized metabolic
      contributor to vascular tone and BP. They imply that (i) metabolites of the
      mevalonate pathway other than cholesterol could potentially control vascular
      functions and cardiovascular hemodynamics, (ii) elevated arterial pressure could
      be in part the consequence of primary disorders of this pathway, and (iii)
      pharmacological inhibition of mevalonate production as a means to lower plasma
      cholesterol may have an adverse impact on other cardiovascular risk factors, such
      as BP.

PMID- 8265618
TI  - A translation-attenuating intraleader open reading frame is selected on
      coronavirus mRNAs during persistent infection.
AB  - Short open reading frames within the 5' leader of some eukaryotic mRNAs are known
      to regulate the rate of translation initiation on the downstream open reading
      frame. By employing the polymerase chain reaction, we learned that the 5'
      terminal 5 nt on the common leader sequence of bovine coronavirus subgenomic
      mRNAs were heterogeneous and hypervariable throughout early infection in cell
      culture and that as a persistent infection became established, termini giving
      rise to a common 33-nt intraleader open reading frame were selected. Since the
      common leader is derived from the genomic 5' end during transcription, a common
      focus of origin for the heterogeneity is expected. The intraleader open reading
      frame was shown by in vitro translation studies to attenuate translation of
      downstream open reading frames in a cloned bovine coronavirus mRNA molecule.
      Selection of an intraleader open reading frame resulting in a general attenuation
      of mRNA translation and a consequent attenuation of virus replication may,
      therefore, be a mechanism by which coronaviruses and possibly other RNA viruses
      with a similar transcriptional strategy maintain a persistent infection.

PMID- 8265619
TI  - Corticosterone in the range of stress-induced levels possesses reinforcing
      properties: implications for sensation-seeking behaviors.
AB  - In both humans and animals certain individuals seek stimuli or situations that
      are considered stressful and consequently avoided by others. A common feature of
      such situations is an activation of the hypothalamo-pituitary-adrenal axis
      leading to secretion of glucocorticoids. Since glucocorticoids have euphoric
      effects in some individuals and have been shown to potentiate the reinforcing
      properties of drugs of abuse in animals, we hypothesized that corticosterone
      secretion during stress-like situations may have reinforcing effects and that a
      higher sensitivity to the reinforcing effects of glucocorticoids might be a
      biological basis of sensation seeking. In this report we show that (i)
      corticosterone has reinforcing properties, as evidenced by the development of
      intravenous self-administration, (ii) self-administration of corticosterone is
      observed at plasma levels that are comparable to those induced by stress, and
      (iii) there are individual differences in corticosterone self-administration,
      which are related to individual reactivity to novelty and sensitivity to drugs of
      abuse, behavioral features akin to certain traits of high-sensation seekers.
      These findings provide insight into the physiological role of glucocorticoids and
      the biology of sensation seeking and may have clinical implications.

PMID- 8265620
TI  - IgG from amyotrophic lateral sclerosis patients increases current through P-type
      calcium channels in mammalian cerebellar Purkinje cells and in isolated channel
      protein in lipid bilayer.
AB  - The effect of the IgG from amyotrophic lateral sclerosis (ALS) patients was
      tested on the voltage-dependent barium currents (IBa) in mammalian dissociated
      Purkinje cells and in isolated P-type calcium channels in lipid bilayers. Whole
      cell clamp of Purkinje cells demonstrates that ALS IgG increases the amplitude of
      IBa without modifying their voltage kinetics. This increased IBa could be blocked
      by a purified nonpeptide toxin from Agelenopsis aperta venom (purified funnel-web
      spider toxin) or by a synthetic polyamine analog (synthetic funnel-web spider
      toxin) and by a peptide toxin from the same spider venom, omega-Aga-IVA. Similar
      results were obtained on single-channel recordings from purified P channel
      protein. The addition of ALS IgG increased single-channel IBa open time without
      affecting slope conductance. The results described above were not seen with
      normal human IgG nor with boiled ALS IgG. It is concluded that ALS IgG enhances
      inward current through P-type calcium channels. Since P-type Ca2+ channels are
      present in motoneuron axon terminals, we propose that the enhanced calcium
      current triggered by ALS IgG may contribute to neuronal damage in ALS.

PMID- 8265621
TI  - Human cytochrome P450 3A4: enzymatic properties of a purified recombinant fusion
      protein containing NADPH-P450 reductase.
AB  - Human cytochrome P450 3A4 is recognized as the catalyst for the oxygen-dependent
      metabolism of a diverse group of medically important chemicals, including the
      immunosuppressive agent cyclosporin; macrolide antibiotics, such as erythromycin;
      drugs such as benzphetamine, nifedipine, and cocaine; and steroids; such as
      cortisol and testosterone to name but a few. We have engineered the cDNA for
      human cytochrome P450 3A4 by linkage to the cDNA for the rat or human
      flavoprotein, NADPH-P450 reductase (NADPH:ferrihemoprotein oxidoreductase, EC
      1.6.2.4). An enzymatically active fusion protein (rF450[mHum3A4/mRatOR]L1) has
      been expressed at high levels in Escherichia coli and purified to homogeneity.
      Enzymatic studies show a requirement for lipid, detergent, and cytochrome b5 for
      the 6 beta-hydroxylation of steroids and the N-oxidation of nifedipine. In
      contrast, these additions are not required for the N-demethylation of
      erythromycin or benzphetamine. A spectrophotometrically detectable metabolite
      complex of P450 3A4 is formed during the metabolism of triacetyloleandomycin, and
      this has a pronounced inhibitory effect on the metabolism of both testosterone
      and erythromycin. These results relate to the interpretation of current methods
      used to assess the in vivo activity of P450 3A4.

PMID- 8265622
TI  - Long-range structural effects in a second-site revertant of a mutant
      dihydrofolate reductase.
AB  - X-ray crystal structures have been determined for a second-site revertant (Asp-27
      ->Ser, Phe-137-->Ser; D27S/F137S) and both component single-site mutants of
      Escherichia coli dihydrofolate reductase. The primary D27S mutation, located in
      the substrate binding pocket, greatly reduces catalytic activity as compared to
      the wild-type enzyme. The additional F137S mutation, which partially restores
      catalytic activity, is located on the surface of the molecule, well outside of
      the catalytic center and approximately 15 A from residue 27. Comparison of
      kinetic data for the single-site F137S mutant, specifically constructed as a
      control, and for the double-mutant enzymes indicates that the effects of the
      F137S and D27S mutations on catalysis are nonadditive. This result suggests that
      the second-site mutation might mediate its effects through a structural
      perturbation propagated along the polypeptide backbone. To investigate the
      mechanism by which the F137S substitution elevates the catalytic activity of D27S
      we have determined the structure of the D27S/F137S double mutant. We also present
      a rerefined structure for the original D27S mutant and a preliminary structural
      interpretation for the F137S single-site mutant. We find that while either single
      mutant shows little more than a simple side-chain substitution, the double mutant
      undergoes an extended structural perturbation, which is propagated between these
      two widely separated sites via the helix alpha B.

PMID- 8265623
TI  - The first step in vision occurs in femtoseconds: complete blue and red spectral
      studies.
AB  - Femtosecond transient absorption measurements of the cis-trans isomerization of
      the visual pigment rhodopsin clarify the interpretation of the dynamics of the
      first step in vision. We present femtosecond time-resolved spectra as well as
      kinetic measurements at specific wavelengths between 490 and 670 nm using 10-fs
      probe pulses centered at 500 and 620 nm following a 35-fs pump pulse at 500 nm.
      The expanded spectral window beyond that available (500-570 nm) in our previous
      study [Schoenlein, R. W., Peteanu, L. A., Mathies, R. A. & Shank, C. V. (1991)
      Science 254, 412-415] provides the full differential absorption spectrum of the
      photoproduct as a function of delay time after photolysis. The high time
      resolution data presented here contradict an alternative interpretation of the
      rhodopsin photochemistry offered by Callender and co-workers [Yan, M., Manor, D.,
      Weng, G., Chao, H., Rothberg, L., Jedju, T. M., Alfano, R. R. & Callender, R. H.
      (1991) Proc. Natl. Acad. Sci. USA 88, 9809-9812]. Our results confirm that the
      red-shifted (lambda max approximately 570 nm) photo-product of the isomerization
      reaction is fully formed within 200 fs. Subsequent changes in the differential
      spectra between 200 fs and 6 ps are attributed to a combination of dynamic ground
      state processes such as intramolecular vibrational energy redistribution,
      vibrational cooling, and conformational relaxation.

PMID- 8265624
TI  - A large cell-adhesive scatter factor secreted by human gastric carcinoma cells.
AB  - Human gastric carcinoma cell line STKM-1 secretes a large protein that induces
      scattering of a rat liver epithelial cell line (BRL) into disconnected individual
      cells in monolayer culture. This cell-scattering factor was purified from serum
      free conditioned medium of STKM-1 cells and found to be composed of three
      disulfide-linked subunits of 140, 150, and 160 kDa. The 140-kDa peptide contains
      an amino acid sequence homologous to that of the laminin B2t chain. The native
      protein has an apparent molecular mass of > 1000 kDa and a pI of 5.0. In addition
      to the cell-scattering activity, the purified protein stimulates attachment of
      BRL cells to substrate and their migration. Similar effects have been observed
      toward various cell lines, including nontumorigenic epithelial, endothelial, and
      fibroblastic cell lines and human cancer cell lines. Similar cell-scattering
      activity was secreted by human squamous carcinoma and gastric carcinoma cell
      lines and nontumorigenic epithelial and endothelial cell lines. These results
      indicate that the protein, named "ladsin," is probably an extracellular matrix
      protein that regulates cell-cell and cell-substrate interactions and cell
      migration.

PMID- 8265625
TI  - Conversion of G-protein specificity of insulin-like growth factor II/mannose 6
      phosphate receptor by exchanging of a short region with beta-adrenergic receptor.
AB  - The 14-residue peptide (peptide 14) corresponding to Arg2410-Lys2423 of the
      insulin-like growth factor II receptor (IGF-IIR) can activate the adenylate
      cyclase-inhibitor guanine nucleotide-binding protein Gi, and the 15-residue beta
      III-2 peptide Arg259-Lys273 of the beta 2-adrenergic receptor (beta 2AR) can
      activate the stimulatory protein Gs. In phospholipid vesicles, IGF-IIR and beta
      2AR activate Gi and Gs in response to IGF-II and isoproterenol, respectively. We
      constructed a chimeric IGF-II receptor (beta III-2/IGF-IIR) by converting its
      native peptide 14 sequence to the beta III-2 sequence. In cells expressing beta
      III-2/IGF-IIR, membrane adenylate cyclase activity markedly increased without IGF
      II and was further promoted by IGF-II. This was verified by measuring
      chloramphenicol acetyltransferase (CAT) activity in beta III-2/IGF-IIR cells with
      cotransfection of a cAMP response element-CAT construct. This study shows not
      only the conversion of G-protein specificity of a receptor from Gi to Gs but also
      the simulation of G protein-coupled receptor signals by using a short receptor
      region and intact cells. These findings indicate that the G protein-activation
      signals are interchangeable, self-determined structural motifs that function in
      the setting of either a single-spanning or multiple-spanning receptor.

PMID- 8265626
TI  - Evolution and expression of a beta-like globin gene of the Australian marsupial
      Sminthopsis crassicaudata.
AB  - A beta-like globin gene was isolated from the Australian dasyurid marsupial
      Sminthopsis crassicaudata. Nucleotide-sequence analysis of promoter and coding
      regions of the gene revealed that it was orthologous to eutherian early-expressed
      (epsilon, gamma, eta) beta-like globin genes. Comparison of the conceptually
      translated sequence of the gene with a partial amino acid sequence of the adult
      beta-globin chain from S. crassicaudata provided evidence that the gene was not
      expressed in adult tissues. In addition, Northern analysis of RNA isolated from
      an embryo, pouch young, and adult bone marrow indicated that the gene was
      expressed predominantly in embryonic tissues and that there was a significant
      reduction in the expression of the gene within a day of birth. These results
      provide strong support for the hypothesis of Koop and Goodman [Koop, B. F. &
      Goodman, M. (1988) Proc. Natl. Acad. Sci. USA 85, 3893-3897] that an embryonic
      beta-like globin gene existed prior to the divergence of the eutherian and
      marsupial lineages and that this gene was already differentiated with respect to
      its promoter regions and developmental expression. The observation that epsilon
      globin mRNA was present at least until day 4 postpartum suggests that the epsilon
      globin chain may play some role in influencing the physiological properties of
      hemoglobin in S. crassicaudata neonates.

PMID- 8265627
TI  - PAS10 is a tetratricopeptide-repeat protein that is essential for the import of
      most matrix proteins into peroxisomes of Saccharomyces cerevisiae.
AB  - pas mutants of Saccharomyces cerevisiae are disturbed in peroxisome assembly
      (pas) and proliferation. Here we report the characterization of the PAS10 gene
      and its product (PAS10) that is essential for the import of a large subset of
      proteins into the peroxisomal matrix. PAS10, a protein of 69 kDa, is a member of
      the tetratricopeptide repeat, or snap helix, protein family, characterized by
      several direct repeats of a degenerate 34-amino acid motif (Sikorski, R. S.,
      Boguski, M. S., Goebl, M. & Hieter, P. (1990) Cell 60, 307-317). Other members of
      this family are MAS70 (S. cerevisiae) and MOM72 (Neurospora crassa), which are
      mitochondrial receptors for protein import. A pas10 null mutant accumulates
      peroxisomal, leaflet-like membrane structures and exhibits deficient import of a
      number of peroxisomal matrix enzymes, particularly of proteins with an SKL-like
      import signal. In contrast, 3-ketoacyl-CoA thiolase associated with these
      membranes is resistant in vitro to degradation by proteinase K, indicating true
      protein import. These results suggest that PAS10 is an essential component of a
      peroxisomal import machinery which mediates the translocation of a specific
      subset of proteins to the peroxisomal matrix with an SKL-like import signal.

PMID- 8265628
TI  - Methotrexate resistance in an in vivo mouse tumor due to a non-active-site
      dihydrofolate reductase mutation.
AB  - A series of methotrexate (MTX)-resistant L1210 leukemia murine ascites tumors
      were developed in vivo and analyzed for drug resistance. Three of 20 tumors
      studied expressed an altered dihydrofolate reductase (DHFR) and each was
      identical, having a C to T base transition at nucleotide 46 in the DHFR gene as
      demonstrated by PCR and direct sequencing. This transition results in a Gly to
      Trp substitution at amino acid 15 of the enzyme. Purified altered enzyme displays
      significantly lower binding affinity for the antifolates MTX, trimetrexate,
      edatrexate, and trimethoprim with respective Ki values 165-, 76-, 30-, and 28
      fold higher than values obtained for enzyme isolated from parental tumor (wild
      type enzyme). Substrate (dihydrofolate) and cofactor (NADPH) binding is also
      diminished for the mutant enzyme, although to a lesser extent (17.3- and 3.6-fold
      higher Km, respectively). Gly-15 is highly conserved for all vertebrate species
      of DHFR but has no known interaction(s), either directly or indirectly, with
      bound cofactor, substrate, or inhibitor. Protein molecular modeling reveals that
      the affected residue is 9-12 A away from the enzyme active site and located in a
      region analogous to the mobile Met-20 loop domain characterized for Escherichia
      coli DHFR.

PMID- 8265629
TI  - Activation of human primary visual cortex during visual recall: a magnetic
      resonance imaging study.
AB  - The degree to which the process involved in visual perception and visual imagery
      share a common neuroanatomical substrate is unclear. Physiological evidence for
      localization of visual imagery early in the visual pathways would have important
      bearing on current theories of visual processing. A magnetic resonance imaging
      technique sensitive to regional changes in blood oxygenation was used to obtain
      functional activation maps in the human visual cortex. During recall of a visual
      stimulus, focal increases in signal related to changes in blood flow were
      detected in V1 and V2 cortex in five of seven subjects. These experiments show
      that the same areas of the early visual cortex that are excited by visual
      stimulation are also activated during mental representation of the same stimulus.
      Some of the processes used in topographically mapped cortical areas during visual
      perception may also be utilized during visual recall.

PMID- 8265630
TI  - Zinc modulation of a transient potassium current and histochemical localization
      of the metal in neurons of the suprachiasmatic nucleus.
AB  - The effect of Zn2+ on a voltage-dependent, transient potassium current (IA) in
      acutely dissociated neurons from the suprachiasmatic nucleus was studied with the
      whole-cell patch-clamp technique. At micromolar concentrations, Zn2+ markedly
      potentiated IA activated from a holding potential of -60 mV, which is the resting
      potential of these neurons. This potentiation occurred at a Zn2+ concentration as
      low as 2 microM and increased with higher Zn2+ concentrations. The Zn2+ action
      appears to arise from a shift in the steady-state inactivation of IA to more
      positive voltages. At 30 microM, Zn2+ shifted the half-inactivation voltage by
      +20 mV (from -80 mV to -60 mV), and 200 microM Zn2+ shifted this voltage by +45
      mV (from -80 mV to -35 mV). Histochemically, we have also observed Zn2+ staining
      throughout the suprachiasmatic nucleus; the staining is particularly intense in
      the ventrolateral region of the nucleus, which receives the major fiber inputs.
      Our findings suggest that Zn2+, presumably synaptically released, may modulate
      the electrical activity of suprachiasmatic nucleus neurons through IA. Because
      vesicular Zn2+ is fairly widespread in the central nervous system, it is
      conceivable that this kind of Zn2+ modulation on IA, and possibly on other
      voltage-activated currents, exists elsewhere in the brain.

PMID- 8265631
TI  - The effect of sequences with high AU content on mRNA stability in tobacco.
AB  - Little is known about the mechanisms that target transcripts for rapid
      degradation in plants. In mammalian cells, sequences with a high AU content and
      multiple AUUUA motifs have been shown to cause mRNA instability when present in
      the 3' untranslated regions of several transcripts. This precedent, coupled with
      the poor accumulation of AU-rich foreign transcripts in plants (e.g., BT-toxin
      mRNAs), prompted us to test whether AU sequences could destabilize transcripts in
      tobacco. To address this question, we made a set of constructs containing
      sequences with high AU content inserted into the 3' untranslated regions of
      reporter genes. The stability of the corresponding transcripts was then assayed
      in stably transformed cell lines of tobacco. These experiments showed that a 60
      base sequence containing 11 copies of the AUUUA motif (AUUUA repeat) markedly
      destabilized a beta-glucuronidase reporter transcript compared to a no-insert
      control or a 60-base spacer sequence (GC control). Another sequence with an
      identical A+U content had little effect. The same results were obtained when each
      sequence was assayed within the 3' untranslated region of a beta-globin reporter
      transcript. In regenerated transgenic plants, the AUUUA repeat decreased the
      accumulation of the beta-globin transcript by approximately 14-fold, compared to
      the GC control. Taken together, our results indicate that the AUUUA repeat is
      recognized as an instability determinant in plant cells and that the effect is
      due to the sequence of the element, not simply to the high AU content.

PMID- 8265632
TI  - Effects of central cholinergic blockade on striatal dopamine release measured
      with positron emission tomography in normal human subjects.
AB  - Previously we demonstrated that positron emission tomography (PET) can be used to
      measure changes in the concentrations of synaptic dopamine and acetylcholine.
      Whether induced directly or indirectly through interactions with other
      neurotransmitters, these studies support the use of PET for investigating the
      functional responsiveness of a specific neurotransmitter to a pharmacologic
      challenge. In an extension of these findings to the human brain, PET studies
      designed to measure the responsiveness of striatal dopamine release to central
      cholinergic blockade were conducted in normal male volunteers using high
      resolution PET and [11C]raclopride, a D2-dopamine receptor antagonist.
      [11C]Raclopride scans were performed prior to and 30 min after systemic
      administration of the potent muscarinic cholinergic antagonist, scopolamine
      (0.007 mg/kg). After scopolamine administration, [11C]raclopride binding
      decreased in the striatum (specific binding) but not in the cerebellum
      (nonspecific binding) resulting in a significant decrease, exceeding the
      test/retest variability of this ligand (5%), in the ratio of the distribution
      volumes of the striatum to the cerebellum (17%). Furthermore, scopolamine
      administration did not alter the systemic rate of [11C]raclopride metabolism or
      the metabolite-corrected plasma input function. These results are consistent not
      only with the known inhibitory influence that acetylcholine exerts on striatal
      dopamine release but also with our initial 18F-labeled N-methylspiroperidol and
      benztropine studies. Thus these data support the use of PET for measuring the
      functional responsiveness of an endogenous neurotransmitter to an indirect
      pharmacologic challenge in the living human brain.

PMID- 8265633
TI  - Metabolic correction and cross-correction of mucopolysaccharidosis type II
      (Hunter syndrome) by retroviral-mediated gene transfer and expression of human
      iduronate-2-sulfatase.
AB  - To explore the possibility of using gene transfer to provide iduronate-2
      sulfatase (IDS; EC 3.1.6.13) enzyme activity for treatment of Hunter syndrome, an
      amphotropic retroviral vector, L2SN, containing the human IDS coding sequence was
      constructed and studied for gene expression in vitro. Lymphoblastoid cell lines
      (LCLs) from patients with Hunter syndrome were transduced with L2SN and expressed
      high levels of IDS enzyme activity, 10- to 70-fold higher than normal human
      peripheral blood leukocytes or LCLs. Such L2SN-transduced LCLs failed to show
      accumulation of 35SO4 into glycosaminoglycan (35SO4-GAG), indicating that
      recombinant IDS enzyme participated in GAG metabolism. Coculture of L2SN
      transduced LCLs with fibroblasts from patients with Hunter syndrome reduced the
      accumulation of 35SO4-GAG. These results demonstrated retroviral-mediated IDS
      gene transfer into lymphoid cells and the ability of such cells to provide
      recombinant enzyme for intercellular metabolic cross-correction.

PMID- 8265634
TI  - Acyclovir diphosphate dimyristoylglycerol: a phospholipid prodrug with activity
      against acyclovir-resistant herpes simplex virus.
AB  - Infection with herpes simplex viruses (HSVs) resistant to treatment with
      acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine, Zovirax) is a growing clinical
      problem in patients with AIDS and other immunosuppressed states. Most virus
      isolates resistant to acyclovir are deficient or defective in virally coded
      thymidine kinase (TK), which converts acyclovir to acyclovir monophosphate in
      virus-infected cells. To restore acyclovir efficacy, we synthesized acyclovir
      diphosphate dimyristoylglycerol, an analog of a naturally occurring phospholipid,
      CDP-diacylglycerol. Its biological activity was tested in WI38 human lung
      fibroblasts infected with the acyclovir-resistant DM21 strain of HSV, which is TK
      negative due to an 816-base-pair deletion in the TK coding region. Acyclovir
      diphosphate dimyristoylglycerol has substantial activity in DM21-infected cells
      (IC50 = 0.25 microM), whereas acyclovir and acyclovir monophosphate were
      ineffective (IC50 > 100 microM). Similar results were obtained in TK-altered and
      TK-deficient strains of HSV-1 and in acyclovir-resistant isolates of HSV-2
      obtained from two AIDS patients. The phospholipid prodrug is active by means of
      TK-independent metabolic pathways that liberate acyclovir monophosphate inside
      the host cell. Acyclovir phosphates were 56 times greater in WI38 human lung
      fibroblasts incubated for 24 hr with [8-3H]acyclovir diphosphate
      dimyristoylglycerol relative to acyclovir. Acyclovir monophosphate added to the
      culture medium (outside the cell) did not circumvent the acyclovir resistance of
      the TK-negative DM21 mutant, presumably due to its conversion to acyclovir by
      phosphatases. Acyclovir diphosphate diacylglycerol prodrugs may be useful in
      treating TK-deficient mutant and wild-type strains of HSV.

PMID- 8265635
TI  - The presequence of Euglena LHCPII, a cytoplasmically synthesized chloroplast
      protein, contains a functional endoplasmic reticulum-targeting domain.
AB  - The precursor to the Euglena light-harvesting chlorophyll a/b-binding protein of
      photosystem II (pLHCPII) is unique; it is a polyprotein, synthesized on membrane
      bound ribosomes and transported to the Golgi apparatus prior to chloroplast
      localization. A cDNA corresponding to the 5' end of LHCPII mRNA has been isolated
      and sequenced. The deduced amino acid sequence of this cDNA indicates that
      Euglena pLHCPII contains a 141-amino acid N-terminal extension. The N-terminal
      extension contains three hydrophobic domains and a potential signal peptidase
      cleavage site at amino acid 35. Cotranslational processing by canine microsomes
      removed approximately 35 amino acids from an in vitro synthesized 33-kDa pLHCPII
      composed of a 141-amino acid N-terminal extension and a 180-amino acid partial
      LHCPII unit truncated at the beginning of the third membrane-spanning hydrophobic
      domain. Processed pLHCPII was degraded by exogenous protease, indicating that it
      had not been translocated to the microsomal lumen. Extraction with 0.1 M Na2CO3,
      pH 11.5, did not remove the processed pLHCPII from the microsomal membrane. A
      stop-transfer membrane anchor sequence appears to anchor the nascent protein
      within the membrane, preventing translocation into the lumen. Taken together,
      these results provide biochemical evidence for a functional cleaved signal
      sequence within the N-terminal extension of a Euglena cytoplasmically synthesized
      chloroplast-localized protein.

PMID- 8265636
TI  - Crystal structure of murine cyclophilin C complexed with immunosuppressive drug
      cyclosporin A.
AB  - Cyclophilin is a cellular receptor for the immunosuppressive drug cyclosporin A
      (CsA). Cyclophilin C (CyPC) is highly expressed in murine kidney, making it a
      potential mediator of the nephrotoxic effects of CsA. The structure of murine
      CyPC complexed with CsA has been solved and refined to an R factor of 0.197 at a
      1.64-A resolution. Superposition of the CyPC-CsA structure with the unligated
      cyclophilin A (CyPA) revealed significant migration of three loops: Gln-179 to
      Thr-189, Asp-47 to Lys-49, and Met-170 to Ile-176. The proximity of the loop Gln
      179 to Thr-189 to the CsA binding site may account for the unique binding of a 77
      kDa glycoprotein, CyPC binding protein (CyCAP), to CyPC. The binding of CsA to
      CyPC is similar to that of CsA to human T-cell cyclophilin A (CyPA). However, the
      conformation of CsA when bound to CyPC is significantly different from that when
      bound to CyPA. These differences may reflect conformational variation of CsA when
      bound to different proteins. Alternatively, the previous CyPA-CsA structure at
      low resolution may not provide sufficient details for a comparison with the CyPC
      CsA structure.

PMID- 8265637
TI  - Protection against chloroethylnitrosourea cytotoxicity by eukaryotic 3
      methyladenine DNA glycosylase.
AB  - A eukaryotic 3-methyladenine DNA glycosylase gene, the Saccharomyces cerevisiae
      MAG gene, was shown to prevent N-(2-chloroethyl)-N-nitrosourea toxicity.
      Disruption of the MAG gene by insertion of the URA3 gene increased the
      sensitivity of S. cerevisiae cells to N-(2-chloroethyl)-N-nitrosourea, and the
      expression of MAG in glycosylase-deficient Escherichia coli cells protected
      against the cytotoxic effects of N-(2-chloroethyl)-N-nitrosourea. Extracts of E.
      coli cells that contain and express the MAG gene released 7-hydroxyethylguanine
      and 7-chloroethylguanine from N-(2-chloroethyl)-N-nitrosourea-modified DNA in a
      protein- and time-dependent manner. The ability of a eukaryotic glycosylase to
      protect cells from the cytotoxic effects of a haloethylnitrosourea and to release
      N-(2-chloroethyl)-N-nitrosourea-induced DNA modifications suggests that mammalian
      glycosylases may play a role in the resistance of tumor cells to the antitumor
      effects of the haloethylnitrosoureas.

PMID- 8265638
TI  - Fast events in protein folding initiated by nanosecond laser photolysis.
AB  - Initiation of protein folding by light can dramatically improve the time
      resolution of kinetic studies. Here we present an example of an optically
      triggered folding reaction by using nanosecond photodissociation of the heme
      carbon monoxide complex of reduced cytochrome c. The optical trigger is based on
      the observation that under destabilizing conditions cytochrome c can be unfolded
      by preferential binding of carbon monoxide to the covalently attached heme group
      in the unfolded state. Photodissociation of the carbon monoxide thus triggers the
      folding reaction. We used time-resolved absorption spectroscopy to monitor
      binding at the heme. Before folding begins we observe transient binding of both
      nonnative and native ligands from the unfolded polypeptide on a microsecond time
      scale. Kinetic modeling suggests that the intramolecular binding of methionine-65
      and -80 is faster than that of histidine-26 and -33, even though the histidines
      are closer to the heme. This optical trigger should provide a powerful method for
      studying chain collapse and secondary structure formation in cytochrome c without
      any limitations in time resolution.

PMID- 8265639
TI  - The minimal self-sufficient element in a murine G+C-rich promoter is a large
      element with imperfect dyad symmetry.
AB  - The murine adenosine deaminase gene has a structurally archetypal TATAA-box
      deficient G+C-rich promoter. The three Sp1 binding sites of the promoter are
      neither necessary nor sufficient for promoter function. Minimal basal promoter
      activity resides within a 48-bp element downstream of the Sp1 binding sites. This
      element shows an imperfect dyad symmetry around the promoter's major
      transcriptional initiation site and contains at least two nuclear protein binding
      sites. The distinctive sequence characteristics and nuclear protein binding
      locations of this element led us to propose a model for how such promoters may
      function.

PMID- 8265640
TI  - Genes in one megabase of the HLA class I region.
AB  - To define the gene content of the HLA class I region, cDNA selection was applied
      to three overlapping yeast artificial chromosomes (YACs) that spanned 1 megabase
      (Mb) of this region of the human major histocompatibility complex. These YACs
      extended from the region centromeric to HLA-E to the region telomeric to HLA-F.
      In addition to the recognized class I genes and pseudogenes and the anonymous non
      class-I genes described recently by us and others, 20 additional anonymous cDNA
      clones were identified from this 1-Mb region. We also identified a long
      repetitive DNA element in the region between HLA-B and HLA-E. Homologues of this
      element were located at several sites in the human genome outside of the HLA
      complex. The portion of the HLA class I region represented by these YACs shows an
      average gene density as high as the class II and class III regions. Thus, the
      high gene density portion of the HLA complex is extended to more than 3 Mb.

PMID- 8265641
TI  - The gamma chain of the high-affinity receptor for IgE is a major functional
      subunit of the T-cell antigen receptor complex in gamma delta T lymphocytes.
AB  - T-cell activation is a consequence of the clonotypic T-cell antigen receptor
      (TCR) binding to an antigen followed by signal transduction via the invariant
      subunits of the TCR/CD3 complex. gamma delta TCR cells are a small subset of T
      cells that populate both the epithelial and lymphoid tissues and have unique
      antigen specificity and function. However, the composition of invariant chains
      within the gamma delta TCR/CD3 complex has not been well characterized. Here we
      report that, unlike the majority of alpha beta T cell, gamma delta T cells
      isolated from spleen and intestinal epithelial tissue express high levels of the
      gamma chain of the high-affinity receptor for IgE (Fc epsilon RI gamma) as one
      invariant subunit of their TCR/CD3 complex. Fc epsilon RI gamma exists as both a
      homodimer and a heterodimer associated with the TCR zeta chain. Moreover,
      stimulation of the gamma delta TCR results in rapid tyrosine phosphorylation of
      Fc epsilon RI gamma. Our results suggest that utilization of distinct receptor
      signaling components may enable the coupling of antigen stimulation to the
      activation of different signal transduction pathways in alpha beta and gamma
      delta T cells.

PMID- 8265642
TI  - Dietary antioxidants preserve endothelium-dependent vessel relaxation in
      cholesterol-fed rabbits.
AB  - Recent evidence suggests that dietary therapy with lipid-soluble antioxidants may
      be beneficial for patients with atherosclerotic vascular disease but the
      potential mechanism(s) for these observations remain obscure. Abnormalities in
      endothelium-dependent control of vascular tone develop early in the course of
      atherosclerosis and may result from oxidative modification of low density
      lipoproteins. We examined the role of dietary antioxidants in preserving normal
      endothelial cell vasodilator function in cholesterol-fed rabbits with particular
      attention to possible effects on serum lipoproteins, low density lipoprotein
      oxidation, and atherogenesis. Male New Zealand White rabbits were fed diets
      containing no additive (controls), 1% cholesterol (cholesterol group), or 1%
      cholesterol chow supplemented with either beta-carotene (0.6 g/kg of chow) or
      alpha-tocopherol (1000 international units/kg of chow) for a 28-day period. After
      dietary therapy, thoracic aortae were harvested for assay of vascular function
      and for pathologic examination and tissue antioxidant levels. Compared to
      controls, acetylcholine- and A23187-mediated endothelium-dependent relaxations
      were significantly impaired in vessels from the cholesterol group (P < 0.001),
      whereas vessels from animals treated with beta-carotene or alpha-tocopherol
      demonstrated normal endothelium-dependent arterial relaxation. Preservation of
      endothelial function was associated with vascular incorporation of alpha
      tocopherol and beta-carotene but was unrelated to plasma lipoprotein levels,
      smooth muscle cell function, or the extent of atherosclerosis. Increased low
      density lipoprotein resistance to ex vivo copper-mediated oxidation was observed
      only in the alpha-tocopherol group. Our results suggest that dietary antioxidants
      may benefit patients with atherosclerosis by preserving endothelial vasodilator
      function through a mechanism related to vascular tissue antioxidant content and
      not reflected by assay of low density lipoprotein resistance to ex vivo
      oxidation.

PMID- 8265643
TI  - Expression and phosphorylation of the Listeria monocytogenes ActA protein in
      mammalian cells.
AB  - Movement of Listeria monocytogenes within infected eukaryotic cells provides a
      simple model system to study the mechanism of actin-based motility in nonmuscle
      cells. The actA gene of L. monocytogenes is required to induce the polymerization
      of host actin filaments [Kocks, C., Gouin, E., Tabouret, M., Berche, P., Ohayon,
      H. & Cossart, P. (1990) Cell 68, 521-531; Domann, E., Wehland, J., Rohde, M.,
      Pistor, S., Hartl, M., Goebel, W., Leimeister-Wachter, M., Wuenscher, M. &
      Chakraborty, T. (1992) EMBO J. 11, 1981-1990]. In this study, an in-frame
      deletion mutation within the actA gene was constructed and introduced into the L.
      monocytogenes chromosome by allelic exchange. This mutation resulted in a
      decrease (3 orders of magnitude) in virulence for mice. In tissue culture cells,
      the actA mutant was absolutely defective for the nucleation of actin filaments
      and consequently was impaired in cell-to-cell spread. Antiserum raised to a
      synthetic peptide encompassing the proline-rich repeat (DFPPPPTDEEL) of ActA was
      used to characterize the expression of the ActA protein. The ActA protein derived
      from extracellular bacteria migrated as a 97-kDa polypeptide upon SDS/PAGE,
      whereas the protein from infected cells migrated as three distinct polypeptides,
      one that comigrated with the 97-kDa extracellular form and two slightly larger
      species. Treatment of infected cells with okadaic acid resulted in decreased
      amounts of all forms of ActA and the appearance of a larger species of ActA.
      Phosphatase treatment of ActA immunoprecipitated from intracellular bacteria
      resulted in conversion of the larger two species to the 97-kDa form. Labeling of
      infected cells with 32Pi followed by immunoprecipitation showed that the largest
      molecular form of ActA was phosphorylated. Taken together, these data indicate
      that ActA is phosphorylated during intracellular growth. The significance of the
      intracellular modification of ActA is not known, but we speculate that it may
      modulate the intracellular activity of ActA.

PMID- 8265644
TI  - Highly localized tracks of human immunodeficiency virus type 1 Nef in the nucleus
      of cells of a human CD4+ T-cell line.
AB  - A human T-cell line constitutively expressing the nef gene from the human
      immunodeficiency virus type 1 SF2 isolate was used to examine the distribution of
      the Nef protein in the nucleus. High-resolution immunogold labeling/electron
      microscopic studies with polyclonal anti-Nef antibodies on nef+ and nef- cells
      revealed that a small fraction of Nef is in the nucleus and it is localized in
      specific curvilinear tracks that extend between the nuclear envelope and the
      nucleoplasm. An examination of the sequence of the SF2 nef gene revealed a
      putative nuclear targeting sequence that was previously found in several other
      eukaryotic nucleoplasmic proteins. The nuclear localization of Nef suggests a
      potential nuclear function for this protein. The presence of Nef in distinct
      nuclear tracks suggests that Nef is transported along a specific pathway that
      extends from the nuclear envelope into the nucleoplasm. A previous study [Meier,
      U. T. & Blobel, G. (1992) Cell 70, 127-138] has shown that the nucleolar protein
      of rat liver cells (Nopp140) shuttles from the nucleolus to the nuclear envelope
      on distinct tracks. The present study has suggested that the transport of a
      nucleoplasmic protein may also occur on distinct nuclear pathways.

PMID- 8265645
TI  - A masculinizing effect on the auditory systems of human females having male co
      twins.
AB  - Spontaneous otoacoustic emissions (SOAEs) are continuous, essentially tonal
      sounds that are produced by many normal-hearing cochleas. In humans, females
      generally exhibit more SOAEs than males, a sex difference that exists from birth.
      However, it is shown here that females having male co-twins [opposite-sex
      dizygotic (OSDZ) females] exhibit about half the average number of SOAEs per ear
      observed in same-sex female twins or female non-twins. Indeed, the average in
      OSDZ females is about the same as that seen in males--twins or non-twins. The
      explanation offered here is that prenatal exposure to high levels of androgens
      has produced a masculinizing effect on the auditory systems of these OSDZ
      females. Prenatal masculinizing effects have long been recognized in certain
      litter-bearing mammals, but their existence in humans is not well-studied.

PMID- 8265647
TI  - Antibody-catalyzed reversal of chemoselectivity.
AB  - A monoclonal antibody, 14D9, which has been elicited against a cationic hapten, N
      alkyl-N-methyl-3-glutarylamidomethyl piperidinium, in which alkyl = [4-(2
      hydroxyethylamido)carbonyl]phenylmethyl, is capable of inverting the intrinsic
      order of reactivity in a series of structurally related enol ethers and ketals
      towards hydrolysis. The order of reactivity of compounds 2 (1-methoxy-2
      alkylcyclopent-1-ene), 3 (1-methoxy-5-alkylcylopent-1-ene), and 4 (1,1-dimethoxy
      2-alkylcyclopentane) has changed from 0.09:0.17:1 in the uncatalyzed reaction to
      1100:25:1 under antibody catalysis. Also, the order of reactivity of the three
      chemically similar ketals, 6a (1-alkyl-2,2-dimethoxypropane), 6b (1-alkyl-1
      methyl-2,2-dimethoxypropane), and 4, has changed from 0.23:0.38:1 in the
      uncatalyzed hydrolysis to 100:9:1 within the antibody active site. As all
      compounds bind the antibody with very similar affinities, these effects cannot be
      simply attributed to selective binding by the antibody. In fact, ketal 4, which
      shows no measurable catalysis, acts as a competitive inhibitor of 14D9-catalyzed
      hydrolysis of 6a. Both the solution and the antibody-catalyzed hydrolysis of the
      ketal substrates are shown to be specific acid catalyzed, involving the
      unimolecular cleavage of the protonated substrate or antibody-substrate complex
      in the rate-determining step. Reactivity effects from the acid catalyst itself on
      ketal hydrolysis (reagent-controlled reactivity) are ruled out under this
      mechanistic scheme.

PMID- 8265646
TI  - Interleukin 6 inhibits mouse placental lactogen II but not mouse placental
      lactogen I secretion in vitro.
AB  - The mouse placenta produces several polypeptides belonging to the prolactin
      growth hormone gene family, including mouse placental lactogen (mPL) I and mPL
      II. The present study was undertaken to determine whether the secretion of mPL-I
      and mPL-II is regulated by interleukin 6 (IL-6), which is present in the placenta
      and has previously been reported to stimulate the secretion of pituitary members
      of this gene family. Effects of human and mouse IL-6 on mPL-I and mPL-II
      secretion were examined in primary cultures of placental cells from days 7, 9,
      and 12 of pregnancy. IL-6 caused a dose-dependent reduction in the mPL-II
      concentration in the medium of cells from days 9 and 12 of pregnancy but did not
      affect the mPL-II concentration in the medium of cells from day 7 of pregnancy or
      the mPL-I concentration in the medium of cells from days 7 or 9 of pregnancy. The
      lowest concentration of human IL-6 that significantly inhibited mPL-II secretion
      was 250 pM. The effect of IL-6 on the mPL-II concentration in the medium was due
      primarily to inhibition of mPL-II synthesis, which resulted at least partly from
      a decrease in the steady-state level of mPL-II mRNA. These data raise the
      possibility that IL-6 may regulate mPL-II production after midpregnancy in vivo.

PMID- 8265648
TI  - Mutational analysis of the helper component-proteinase gene of a potyvirus:
      effects of amino acid substitutions, deletions, and gene replacement on virulence
      and aphid transmissibility.
AB  - We have previously provided evidence that amino acid substitutions within the N
      terminal portion of the helper component-proteinase (HC-Pro) from tobacco vein
      mottling virus (TVMV), in particular at Lys-307, not only affect the aphid
      transmission activity of HC-Pro but also have a significant effect on TVMV
      virulence. In the present study amino acids which differ in their charge
      properties were substituted at position 307. A highly basic residue was required
      to retain helper component activity and virulence. Deletion and insertion
      mutagenesis in the 5' terminus of the HC-Pro gene suggested that this RNA domain
      may be an essential element for TVMV infectivity. Replacement of the TVMV HC-Pro
      gene with that from another potyvirus, zucchini yellow mosaic virus, maintained
      infectivity and aphid transmissibility of the chimeric virus, although symptoms
      were attenuated. Our results suggest that, in addition to its importance in aphid
      transmission, the HC-Pro gene may be of general importance in regulating
      virulence of potyviruses, possibly by interaction of these sequences with the
      host.

PMID- 8265649
TI  - Soluble interleukin-6 receptor triggers osteoclast formation by interleukin 6.
AB  - It has been reported that soluble interleukin (IL)-6 receptor (sIL-6R) is
      detected in the serum of healthy individuals and its level is increased in
      patients with multiple myeloma and human immunodeficiency virus infection.
      Although several reports have suggested that sIL-6R potentiates IL-6 action, its
      physiological role remains unclear. In this study, we examined the role of sIL-6R
      on osteoclast formation by IL-6, using a coculture of mouse osteoblasts and bone
      marrow cells. Neither recombinant mouse IL-6 (mIL-6) nor mouse sIL-6R (smIL-6R)
      induced osteoclast-like multinucleated cell (MNC) formation when they were added
      separately. In contrast, simultaneous treatment with mIL-6 and smIL-6R strikingly
      induced MNC formation. These MNCs satisfied major criteria of authentic
      osteoclasts, such as tartrate-resistant acid phosphatase (TRAP) activity,
      calcitonin receptors, and pit formation on dentine slices. The MNC formation
      induced by mIL-6 and smIL-6R was dose-dependently inhibited by adding monoclonal
      anti-mouse IL-6R antibody (MR16-1). It is likely that osteoblasts and osteoclast
      progenitors are capable of transducing a signal from a complex of IL-6 and sIL-6R
      through gp130, even though they may have no or a very small number of IL-6Rs.
      Factors such as IL-11, oncostatin M, and leukemia inhibitory factor, which are
      known to exert their functions through gp130 (the signal-transducing chain of IL
      6R), also induced MNC formation in our coculture system. These results suggest
      that increased circulating or locally produced sIL-6R induces osteoclast
      formation in the presence of IL-6 mediated by a mechanism involving gp130. This
      may play an important physiological or pathological role in conditions associated
      with increased osteoclastic bone resorption.

PMID- 8265650
TI  - Correlations between isochores and chromosomal bands in the human genome.
AB  - The human genome is made up of long DNA segments, the isochores, which are
      compositionally homogeneous and can be subdivided into a small number of families
      characterized by different G+C levels. Chromosome in situ suppression
      hybridization (in which excess unlabeled human DNA is added to suppress
      hybridization of repeated sequences present in the probe, enabling enhanced
      observation of single-copy sequences) of DNA fractions characterized by an
      increasing G+C level was carried out to determine the distribution of "single
      copy" sequences corresponding to isochore families L1+L2, H1, H2, and H3 on
      metaphase chromosomes. This produced a banding pattern progressing from a
      relatively diffuse staining to an R-banding, to a T-banding. More specifically,
      our results showed that (i) T-bands are formed by the G+C-richest isochores of
      the H3 family and by part of the G+C-rich isochores of the H1 and H2 families
      (with a predominance of the latter); (ii) R'-bands (namely, R-bands exclusive of
      T-bands) are formed to almost equal extents by G+C-rich isochores of the H1
      families (with a minor contribution of the H2 and H3 families) and by G+C-poor
      isochores of the L1+L2 families; (iii) G-bands essentially consist of G+C-poor
      isochores from the L1+L2 families, with a minor contribution of isochores from
      the H1 family. These results not only clarify the correlations between DNA base
      composition and chromosomal bands but also provide information on the
      distribution of genes in chromosomes, gene concentration increasing with the G+C
      levels of isochores.

PMID- 8265651
TI  - A neo-Darwinian algorithm: asymmetrical mutations due to semiconservative DNA
      type replication promote evolution.
AB  - Evolution is, in a sense, to resolve optimization problems. Our neo-Darwinian
      algorithm based on the mechanics of inheritance and natural selection uses double
      stranded DNA-type genetic information to resolve the "knap-sack problem." The
      algorithm with asymmetrical mutations due to semiconservative DNA-type
      replication most effectively resolved the problem. Our results strongly suggest
      that disparity in mutations caused by the asymmetric machinery of DNA replication
      promotes evolution, in particular of diploid organisms with a high mutation rate,
      in a small population, and under strong selection pressure.

PMID- 8265652
TI  - Biotinylated diaminopyridine: an approach to tagging oligosaccharides and
      exploring their biology.
AB  - Fluorescent tagging of free oligosaccharides by reductive amination permits
      sensitive detection and fractionation of these molecules. To expand the scope of
      this approach, we have synthesized a fluorescent reagent, 2-amino-(6
      amidobiotinyl)pyridine. This reagent can tag oligosaccharides under
      nondegradative conditions with high efficiency. The resulting adducts show
      excellent fractionation by reverse-phase HPLC with sensitive detection in the low
      picomole range. When combined with sequential exoglycosidase digestion, stepwise
      sequencing of the sugar chains is possible. The biotinyl group can also be used
      to recover the sugar chain from reaction mixtures. The high-affinity interaction
      of the biotinyl group with multivalent avidin or streptavidin can be used to
      create the functional equivalent of neoglycoproteins carrying multiple copies of
      oligosaccharides of defined structure. These complexes allow the production of
      IgG antibodies directed against the oligosaccharide chain. They can also harness
      the power of (strept)avidin-biotin technology for the detection and isolation of
      oligosaccharide-specific receptors from native sources of recombinant libraries.

PMID- 8265653
TI  - Mathematical textbook of deformable neuroanatomies.
AB  - Mathematical techniques are presented for the transformation of digital
      anatomical textbooks from the ideal to the individual, allowing for the
      representation of the variabilities manifest in normal human anatomies. The ideal
      textbook is constructed on a fixed coordinate system to contain all of the
      information currently available about the physical properties of neuroanatomies.
      This information is obtained via sensor probes such as magnetic resonance, as
      well as computed axial and emission tomography, along with symbolic information
      such as white- and gray-matter tracts, nuclei, etc. Human variability associated
      with individuals is accommodated by defining probabilistic transformations on the
      textbook coordinate system, the transformations forming mathematical translation
      groups of high dimension. The ideal is applied to the individual patient by
      finding the transformation which is consistent with physical properties of
      deformable elastic solids and which brings the coordinate system of the textbook
      to that of the patient. Registration, segmentation, and fusion all result
      automatically because the textbook carries symbolic values as well as multisensor
      features.

PMID- 8265654
TI  - Immunocytochemical localization of the plasma membrane calcium pump, calbindin
      D28k, and parvalbumin in Purkinje cells of avian and mammalian cerebellum.
AB  - A monoclonal antibody produced against the human erythrocyte plasma membrane
      calcium pump (PMCA) was shown to react immunohistochemically with an epitope of
      the PMCA in avian and mammalian cerebellum. Western blot analysis of purified
      synaptosomes and homogenates from avian cerebellum revealed major immunoreactive
      proteins with molecular masses (130 kDa and 138 kDa) similar to those of purified
      erythrocyte PMCA. Dual-imaging confocal immunofluorescence microscopy of avian
      cerebellum showed that the PMCA antibody stained the periphery of the soma
      whereas calbindin-D28k was located in the cytosol. PMCA heavily stained the more
      distal dendrites of the Purkinje cells and, within the resolution of the
      fluorescence procedure, colocalized with calbindin-D28k. By using alkaline
      phosphatase-conjugated second antibody, PMCA was again localized to the
      peripheral soma, to a segmental pattern in dendrites, and to presumed spiny
      elements. The soma periphery and dendrites of Purkinje cells of the rat
      cerebellum were also prominently stained with anti-PMCA antibody and compared to
      parvalbumin localization. Dendritic depolarization and dendritic spiking behavior
      are significant Ca(2+)-dependent events of Purkinje cells. The rapid decline of
      intracellular free Ca2+ after the rapid rise time of Ca2+ transients is
      considered to be due to sequestration by Ca2+ buffers, uptake by intracellular
      stores, and Ca2+ extrusion mechanisms, the latter a function of PMCA now shown
      immunohistochemically to be a prominent feature of Purkinje cell dendrites.

PMID- 8265655
TI  - Transcriptional regulatory elements downstream of the JunB gene.
AB  - JunB is an immediate early transcription factor that is induced by a variety of
      extracellular signaling agents, including growth factors, phorbol esters, and
      agents that elevate cyclic AMP. The mechanism of activation of the gene encoding
      JunB by these agents is not well understood. By using the JunB gene together with
      flanking DNA in transfection experiments, we show that a serum response element
      (SRE) and/or a cAMP response element (CRE) downstream of the gene mediate the
      response of the gene in mouse NIH 3T3 cells to serum, platelet-derived growth
      factor, basic fibroblast growth factor, phorbol ester, and forskolin. In
      addition, a segment of DNA just upstream of the TATA box is required for optimal
      activation of the gene.

PMID- 8265656
TI  - Single photon emission computed tomographic imaging demonstrates loss of striatal
      dopamine transporters in Parkinson disease.
AB  - [123I][(1R)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane] ([123I]beta-CIT)
      labels dopamine transporters and is, therefore, a marker of neurons that
      degenerate in Parkinson disease. Single photon emission computed tomography
      imaging with [123I]beta-CIT showed that radioactivity in striatal regions in
      healthy subjects increased during a 2-day imaging study, whereas that in
      Parkinsonian patients peaked earlier at reduced levels relative to healthy
      subjects. Kinetic analyses of radioactivity in plasma and brain suggest that this
      decrease was due to an approximately 65% loss of target sites in patients
      compared with healthy subjects; greater losses occurred in putamen than in
      caudate. All patients showed lateralized differences in striatal uptake, with
      greater losses in the striatum contralateral to the side of the body with initial
      symptoms. These preliminary results suggest that [123I]beta-CIT is a marker for
      the loss of striatal dopamine terminals in patients with Parkinson disease.
      Single photon emission computed tomographic imaging with [123I]beta-CIT may be
      useful for early diagnosis of the disorder, for monitoring the progression of the
      disease, and for distinguishing the idiopathic disorder from other Parkinsonian
      syndromes with more widespread pathology.

PMID- 8265657
TI  - Aspartate transcarbamoylase containing circularly permuted catalytic polypeptide
      chains.
AB  - Based on the demonstration that active enzyme is formed in vitro and in vivo from
      polypeptide fragments of the catalytic chains of aspartate transcarbamoylase
      (ATCase; EC 2.1.3.2) and the evidence that NH2 and COOH termini of wild-type
      chains are in close proximity, we constructed altered genes to determine whether
      circularly permuted catalytic chains could fold and assemble into active
      catalytic trimers. Two slightly different genetic constructs led to the
      expression in good yield of circularly permuted catalytic chains, which
      associated in vivo into active trimers. They, in turn, combined in vitro with
      wild-type regulatory dimers to form ATCase-like molecules. Both polypeptide
      chains began at residue 235 in a different domain from the NH2 terminus of wild
      type and had an overlapping sequence of eight residues at the COOH terminus. One
      had a six-amino-acid linker, and the other had a deletion of four residues.
      Enzymes containing rearranged chains were similar to their wild-type counterparts
      in physical properties. Whereas values of Vmax were close to those of wild-type
      trimers and ATCase, the Km values were more than 10-fold greater. Also the
      allosteric properties characteristic of wild-type ATCase were lacking in the
      enzymes containing permuted chains. Denaturation of trimers by urea was
      reversible, and recovery of activity in both rate and yield was comparable to
      that of wild-type trimers. The experiments demonstrate that folding of chains
      into clearly defined domains and the assembly of active, thermodynamically stable
      oligomers are not dependent on the positions of NH2 and COOH termini; the folded
      structures are a consequence of the final sequence and not the order of
      biosynthetic addition of amino acids.

PMID- 8265658
TI  - Two functionally distinct forms of the photosystem II reaction-center protein D1
      in the cyanobacterium Synechococcus sp. PCC 7942.
AB  - The cyanobacterium Synechococcus sp. PCC 7942 possesses a small psbA multigene
      family that codes for two distinct forms of the photosystem II reaction-center
      protein D1 (D1:1 and D1:2). We showed previously that the normally predominant D1
      form (D1:1) was rapidly replaced with the alternative D1:2 when cells adapted to
      a photon irradiance of 50 mumol.m-2.s-1 are shifted to 500 mumol.m-2.s-1 and that
      this interchange was readily reversible once cells were allowed to recover under
      the original growth conditions. By using the psbA inactivation mutants R2S2C3 and
      R2K1 (which synthesize only D1:1 and D1:2, respectively), we showed that this
      interchange between D1 forms was essential for limiting the degree of
      photoinhibition as well as enabling a rapid recovery of photosynthesis. In this
      report, we have extended these findings by examining whether any intrinsic
      functional differences exist between the two D1 forms that may afford increased
      resistance to photoinhibition. Initial studies on the rate of D1 degradation at
      three photon irradiances (50, 200, and 500 mumol.m-2.s-1) showed that the rates
      of degradation for both D1 forms increase with increasing photon flux density but
      that there was no significant difference between D1:1 and D1:2. Analysis of light
      response curves for oxygen evolution for the mutants R2S2C3 and R2K1 revealed
      that cells with photosystem II reaction centers containing D1:2 have a higher
      apparent quantum yield (approximately 25%) than cells possessing D1:1. Further
      studies using chlorophyll a fluorescence measurements confirmed that R2K1 has a
      higher photochemical yield than R2S2C3; that is, a more efficient conversion of
      excitation energy from photon absorption into photochemistry. We believe that the
      higher photochemical efficiency of reaction centers containing D1:2 is causally
      related to the preferential induction of D1:2 at high light and thus may be an
      integral component of the protection mechanism within Synechococcus sp. PCC 7942
      against photoinhibition.

PMID- 8265659
TI  - The SRY high-mobility-group box recognizes DNA by partial intercalation in the
      minor groove: a topological mechanism of sequence specificity.
AB  - SRY, a putative transcription factor encoded by the sex-determining region of the
      human Y chromosome, regulates a genetic switch in male development. Impairment of
      this switch leads to intersex abnormalities of the newborn and is observed in
      association with mutations in the SRY DNA-binding domain [the high-mobility-group
      (HMG) box]. Here we show that the SRY HMG box exhibits a novel mechanism of DNA
      recognition: partial intercalation of a nonpolar side chain in the DNA minor
      groove. Base stacking (but not base pairing) is interrupted at the site of
      insertion. Sequence specificity reflects topological requirements of partial
      intercalation rather than direct readout of base-specific functional groups. Our
      results predict that the SRY HMG box inserts an alpha-helix into a widened minor
      groove at the center of a sharp DNA bend. A similar mechanism may underlie
      binding of SRY and homologous HMG proteins to four-way junctions (Holliday
      intermediates) and other noncanonical DNA structures.

PMID- 8265660
TI  - HLA-C is the inhibitory ligand that determines dominant resistance to lysis by
      NK1- and NK2-specific natural killer cells.
AB  - Natural killer (NK) cells recognize alloantigens on normal cells. One of these
      alloantigens correlates with homozygosity for a dimorphism of HLA-C at positions
      77-80, which is shared by a number of HLA-C alleles. A second allelic alloantigen
      correlates with homozygosity for the alternative HLA-C dimorphism, which is
      shared by the remaining HLA-C alleles. Moreover, NK1- and NK2-specific NK cell
      lines can be generated by mixed leukocyte cultures in which donor and stimulator
      are homozygous for the alternative dimorphisms at positions 77-80 of HLA-C. In
      the present work, the role of HLA-C in NK cell-mediated allorecognition was
      directly investigated by analyzing the effects produced by transfection of
      several HLA-C alleles on NK sensitivity of class I-deleted mutant cell lines.
      Transfection of cells with HLA-C alleles encoding Asn-77-Lys-80 (including HLA
      Cw4, -Cw5, and -Cw6) inhibited the lysis of the targets by NK1-specific NK cells,
      whereas HLA-C alleles encoding Ser-77-Asn-80 (including HLA-Cw1, -Cw7, and -Cw13)
      protected the targets from NK2-specific NK cells. Thus, HLA-C alleles are the
      dominant inhibitory ligands that protect targets from lysis by these allospecific
      NK cells.

PMID- 8265661
TI  - Allele-specific peptide ligand motifs of HLA-C molecules.
AB  - The consensus motifs of HLA-Cw3, -Cw4, -Cw6, and -Cw7 ligands were determined by
      pool sequencing. Together with information obtained by sequencing of some
      prominent individual peptides, the results indicate the following: (i) all four
      HLA-C molecules are associated with peptides. (ii) These peptides adhere to
      allele-specific motifs that are similar to those of to HLA-A or -B molecules;
      they have a preferred length of nine amino acids and an anchor residue at the C
      terminus. (iii) All four HLA-C molecules analyzed exhibit related peptide motifs,
      although each allelic product shows individual characteristics in fine
      specificity. (iv) Processing and origin of peptides appear not to be different
      from that of other class I molecules. (v) No obvious difference at C-terminal
      position 9 was present in the peptides isolated from the two dimorphic variants
      of HLA-C that determine dominant resistance to natural killer NK1-specific cells
      (HLA-Cw4, -Cw6) or to NK2-specific cells (HLA-Cw3, -Cw7) and that differ in two
      residues in or near the pocket at position 9.

PMID- 8265662
TI  - Role of intermolecular/intrastructural B- and T-cell determinants in the
      diversification of autoantibodies to ribonucleoprotein particles.
AB  - The U1 small nuclear ribonucleoprotein (sn-RNP) particle, which consists of the
      U1 small RNA and multiple polypeptides, is a central target of the autoimmune
      response in systemic lupus erythematosus. Autoantibodies to the individual
      proteins of the U1 snRNP typically co-occur in patients with systemic lupus
      erythematosus, an observation reconciled by postulating that the intact RNA
      protein complex serves as the autoimmunogen and that snRNP-specific autoreactive
      T cells are necessary for autoantibody production. In this study, we demonstrated
      that normal mice did not develop antibody responses following immunization with
      purified self (murine) snRNPs. However, when such mice were coimmunized with self
      snRNPs in conjunction with the human (foreign) U1 snRNP A protein, they developed
      autoantibodies directed against individual proteins of the U1 snRNP, in addition
      to anti-A antibodies; we have previously shown that such mice develop snRNP
      specific, autoreactive T cells. Intact snRNPs as a co-immunogen were a
      prerequisite for antibody expansion, since this response was abrogated by
      disruption of snRNP particles with pancreatic RNase prior to immunization. These
      findings indicate that autoreactive helper T cells can drive autoantibody
      production to the individual proteins of snRNP particles and that such
      autoantibody responses may require the presence of intact snRNP particles that
      possess intrastructural B-cell and helper-T-cell determinants. These results also
      suggest that induction of an immune response to one component of an autoantigenic
      snRNP complex, possibly through priming with molecular mimics, can induce the
      diversification of autoantibodies that is characteristic of that found in
      patients with systemic lupus erythematosus.

PMID- 8265663
TI  - Unresponsiveness of primitive chronic myeloid leukemia cells to macrophage
      inflammatory protein 1 alpha, an inhibitor of primitive normal hematopoietic
      cells.
AB  - Most primitive hematopoietic cells appear to be normally quiescent in vivo,
      whereas their leukemic counterparts in patients with chronic myeloid leukemia
      (CML) are maintained in a state of rapid turnover. This difference is also seen
      in the long-term culture system, where control of primitive hematopoietic
      progenitor proliferation is mediated by interactions of these cells with marrow
      derived mesenchymal cells of the fibroblast lineage. We now show that exogenous
      addition of macrophage inflammatory protein 1 alpha (MIP-1 alpha) to normal long
      term cultures can reversibly and specifically block the activation of "primitive"
      (high proliferative potential), but not "mature" (lower proliferative potential),
      progenitors in the adherent layer of these cultures. Moreover, addition of MIP-1
      beta after primitive-progenitor activation can prevent the subsequent return of
      these cells to a quiescent state a few days later as shown previously in similar
      experiments using antibodies to transforming growth factor beta. This suggests
      that the level of MIP-1 alpha (or a related MIP-1 alpha agonist) produced in
      LTCs, like the level of transforming growth factor beta, may be necessary, but is
      not on its own sufficient, to mediate the inhibitory activity of the regulatory
      cells in the adherent layer. Addition of MIP-1 alpha to similar long-term
      cultures containing normal marrow adherent layers but supporting exclusively
      neoplastic (CML) hematopoiesis did not block the cycling of primitive neoplastic
      progenitors. A defect in the responsiveness of CML cells to MIP-1 alpha (or a
      similarly acting chemokine) would explain their deregulated proliferative
      behavior in this model and, by extrapolation to the in vivo setting, suggests a
      molecular mechanism whereby the leukemic clone may become amplified at the stem
      cell level. In addition, these findings suggest approaches to the therapy of CML,
      using inhibitors such as MIP-1 alpha for the protection of primitive normal
      cells.

PMID- 8265664
TI  - Cloning and characterization of subunit genes of ribonucleotide reductase, a cell
      cycle-regulated enzyme, from Plasmodium falciparum.
AB  - Ribonucleotide reductase (EC 1.17.4.1; RNR), a cell-cycle-regulated enzyme,
      catalyzes the rate-limiting step in the de novo synthesis of deoxyribonucleotides
      by the reduction of the corresponding ribonucleotides. The important role of the
      RNR in DNA synthesis and cell division makes this enzyme an excellent target for
      chemotherapy. However, nothing is known about this enzyme from the malaria
      parasite Plasmodium falciparum. We have isolated cDNA clones encoding both the
      large and small RNR subunits. The sequences of full-length clones of the large
      and small RNR subunits revealed an open reading frame encoding 806 and 349 amino
      acids, respectively, and showed significant identity with other RNR sequences in
      the data base. RNA blot analysis showed that the size of the large and small RNR
      subunit transcripts are 5.4 kb and 2.2 kb, respectively. Both the RNR subunit
      transcripts fluctuate in level during the cell cycle, reaching a peak preceding
      maximal DNA synthesis activity. An oligodeoxynucleotide phosphorothioate that is
      complementary to sequences around the translational initiation codon of the small
      RNR subunit showed significant inhibition of growth, as measured by the
      inhibition in DNA synthesis.

PMID- 8265665
TI  - Deficient transcription of XIST from tiny ring X chromosomes in females with
      severe phenotypes.
AB  - The severe phenotype of human females whose karyotype includes tiny ring X
      chromosomes has been attributed to the inability of the small ring X chromosome
      to inactivate. The XIST locus is expressed only from the inactive X chromosome,
      resides at the putative X inactivation center, and is considered a prime player
      in the initiation of mammalian X dosage compensation. Using PCR, Southern blot
      analysis, and in situ hybridization, we have looked for the presence of the XIST
      locus in tiny ring X chromosomes from eight females who have multiple congenital
      malformations and severe mental retardation. Our studies reveal heterogeneity
      within this group; some rings lack the XIST locus, while others have sequences
      homologous to probes for XIST. However, in the latter, the locus is either not
      expressed or negligibly expressed, based on reverse transcription-PCR analysis.
      Therefore, what these tiny ring chromosomes have in common is a level of XIST
      transcription comparable to an active X. As XIST transcription is an indicator of
      X chromosome inactivity, the absence of XIST transcription strongly suggests that
      tiny ring X chromosomes in females with severe phenotypes are mutants in the X
      chromosome inactivation pathway and that the inability of these rings to
      inactivate is responsible for the severe phenotypes.

PMID- 8265666
TI  - The gene responsible for Werner syndrome may be a cell division "counting" gene.
AB  - Werner syndrome is a rare, autosomal, recessive condition that is frequently
      studied as a model of some aspects of human aging, although the behavioral
      changes that are usually associated with old age are only seen very infrequently.
      A most striking aspect of the phenotype of Werner syndrome, presumably arising
      from the same gene defect, is a dramatic shortening of the replicative life-span
      of dermal fibroblasts in vitro. The finite replicative life-span of human cells
      in vitro is due to the stochastic loss of replicative ability in a continuously
      increasing fraction of newborn cells at every generation. Normal human
      fibroblasts achieve approximately 60 population doublings in culture, while
      Werner syndrome cells usually only achieve approximately 20 population doublings.
      We describe an analysis of the replicative ability of fibroblasts from Werner
      syndrome patients and demonstrate that the cells in these cultures usually exit,
      apparently irreversibly, from the cell cycle at a faster rate than do normal
      cells, although they mostly start off with a good replicative ability. We propose
      that the Werner syndrome gene is a "counting" gene controlling the number of
      times that human cells are able to divide before terminal differentiation.

PMID- 8265667
TI  - In vivo protection against endotoxin by plasma high density lipoprotein.
AB  - Overwhelming bacterial infection is accompanied by fever, hypotension,
      disseminated intravascular coagulation, and multiple organ failure leading to
      death in 30-80% of cases. These classical symptoms of septic shock are caused by
      potent cytokines that are produced in response to endotoxin released from Gram
      negative bacteria. Treatments with antibodies and receptor antagonists to block
      endotoxin or cytokine mediators have given mixed results in clinical trials. High
      density lipoprotein (HDL) is a natural component of plasma that is known to
      neutralize endotoxin in vitro. We report here that raising the plasma HDL
      concentration protects mice against endotoxin in vivo. Transgenic mice with 2
      fold-elevated plasma HDL levels had more endotoxin bound to HDL, lower plasma
      cytokine levels, and improved survival rates compared with low-HDL mice.
      Intravenous infusion of HDL also protected mice, but only when given as
      reconstituted HDL prepared from phospholipid and either HDL apoprotein or an 18
      amino acid peptide synthesized to mimic the structure of apolipoprotein A-I of
      HDL. Intact plasma HDL was mildly toxic, and HDL apoprotein was ineffective. The
      effectiveness of the reconstituted peptide renders very unlikely any significant
      contribution to protection by trace proteins in apo-HDL. These data suggest a
      simple leaflet insertion model for binding and neutralization of
      lipopolysaccharide by phospholipid on the surface of HDL. Plasma HDL may normally
      act to protect against endotoxin; this protection may be augmented by
      administration of reconstituted HDL or reconstituted peptides.

PMID- 8265668
TI  - apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta
      amyloid protein precursor.
AB  - The major component of senile plaques found in the brains of Alzheimer disease
      patients is the beta-amyloid peptide, which is derived from a larger amyloid
      precursor protein (APP). Recently, a number of APP and APP-related proteins have
      been identified in different organisms and constitute the family of APP proteins.
      We have isolated several cDNAs encoding an APP-related protein in the nematode
      Caenorhabditis elegans and have designated the corresponding gene as apl-1. The
      apl-1 transcripts undergo two forms of posttranscriptional modification: trans
      splicing and alternative polyadenylylation. In vitro translation of an apl-1 cDNA
      results in a protein of approximately the expected size. Similar to the
      Drosophila, human, and mouse APP-related proteins, APL-1 does not appear to
      contain the beta-amyloid peptide. Because APP-related proteins seem to be
      conserved through evolution, the apl-1 gene from C. elegans should be important
      for determining the normal function of human APP.

PMID- 8265669
TI  - Protein kinase C and F1/GAP-43 gene expression in hippocampus inversely related
      to synaptic enhancement lasting 3 days.
AB  - The mRNA levels of protein F1 (also known as GAP-43), and protein kinase C (PKC)
      subtypes were measured 3 days after the induction of long-term enhancement (also
      known as long-term potentiation) in the hippocampus of chronically prepared
      conscious rats by quantitative in situ hybridization. Altered mRNA levels
      correlated significantly with alternations in synaptic efficacy; such
      correlations have not been reported previously. Rats with greater synaptic
      enhancement had lower gene expression in the CA3 subfield of F1/GAP-43 and both
      beta-PKC and gamma-PKC, but not alpha-PKC. For microtubule-associated protein 2
      (MAP-2), neurogranin, and the glutamate receptor subtype B-flip, no correlation
      was observed in any cell field between synaptic enhancement and hybridization to
      the mRNA. To our surprise, alterations in mRNA levels of F1/GAP-43 and gamma-PKC
      were highly correlated (r = +0.928, P < 0.001), suggesting coordinate regulation.
      Since F1/GAP-43 is associated with neurite growth, its lowered expression at 3
      days would reduce potential growth, leading to synaptic stabilization. We propose
      that long-term synaptic change is mediated by gene expression of the very same
      proteins initially modified posttranslationally.

PMID- 8265670
TI  - Detection of alpha-subunit isoforms in human muscle acetylcholine receptor by
      specific T cells from a myasthenia gravis patient.
AB  - The nicotinic acetylcholine receptor (AChR) is both the best-characterized
      transmitter receptor-ion channel and the target for the pathogenic antibodies in
      the human autoimmune disease myasthenia gravis (MG). In cloning and sequencing
      its components in man, we found that the alpha-subunit was transcribed in two
      isoforms, with (P3A+) or without (P3A-) a 75 base pair exon that had not been
      described in other species. While studying the human T lymphocyte response to
      recombinant AChR, we found that part of this P3A insert was recognized by one T
      cell line (from an MG patient), whereas another line only recognized the
      uninterrupted insertion site. To establish whether this exon is also translated
      in normal human muscle, we initially raised anti-peptide antibodies to the
      relevant amino acid sequences, but these failed to bind native AChR (affinity
      purified from muscle on alpha-neurotoxin columns). We therefore exploited the
      great sensitivity and specificity of these T cells to detect the two isoforms
      after unfolding by antigen-presenting cells, and have been able to show that both
      are expressed in affinity-purified human muscle AChR.

PMID- 8265671
TI  - Positive regulation by protein kinase C of slow Na current in Xenopus oocytes.
AB  - The slow inward Na current observed during sustained depolarization of the
      Xenopus oocyte membrane is due to a complex mechanism described as the induction
      of the channels. The present work investigates the role of protein
      phosphorylation in Na channel function. Injection of alkaline phosphatase in the
      oocytes decreased inward current. Therefore, the possible involvement of protein
      kinase in Na channel induction was explored. Treatment of oocytes with two
      activators of protein kinase C (PKC) resulted in enhanced Na current amplitude,
      whereas the treatment of oocytes with two potent PKC inhibitors decreased the
      inward current. These results imply that PKC phosphorylation is a fundamental
      step of Na channel induction. The possibility that the depolarization of the
      oocyte membrane may be the factor involved in PKC activation is discussed.

PMID- 8265672
TI  - Melatonin and photoperiodic time measurement in Japanese quail (Coturnix coturnix
      japonica).
AB  - Artificial extension of the duration of nocturnally secreted circulating
      melatonin with exogenous injections produces a short day effect in the
      reproductive status of mammals, and this paradigm has been applied to Japanese
      quail to test the hypothesis that birds are similar to mammals in this respect.
      Male quail reared on non-stimulatory short days (8L:16D) were switched to mildly
      stimulatory 12L:12D and given daily melatonin injections at dusk (10 micrograms 2
      h before dusk and 10 micrograms at dusk) or at dawn (10 micrograms 2 h before
      dawn and 10 micrograms at dawn) for about 3 weeks. Although assay of circulating
      melatonin suggested that injections had extended the melatonin signal, there was
      no short day effect, i.e. reproductive stimulation was not prevented. This
      reinforces the view that, unlike mammals, birds do not read the duration of the
      melatonin signal to measure scotoperiod. Paradoxically, however, the injections
      resulted in a small but significant stimulation. The results are discussed in
      view of the postulated role for melatonin as an internal Zeitgeber, which is
      coupled to the external photic Zeitgeber, to regulate the circadian system.

PMID- 8265673
TI  - Malnutrition, age and the risk of parasitic disease: visceral leishmaniasis
      revisited.
AB  - Children are said to be at greater risk of developing visceral leishmaniasis (VL)
      when they are younger and more malnourished. If malnutrition really is associated
      with VL, this potentially fatal and visible disease may be a general indicator of
      community health among the rural and suburban poor. Previous conclusions reached
      about the roles of malnutrition and age in VL epidemiology are questionable
      because they may have been confounded by transmission rate, because they have not
      been able to distinguish between different mechanisms of acquiring immunity, and
      because empirical observations have not been compared with theoretical
      expectations. Here we offer a framework with which to investigate these questions
      quantitatively, and do so with published data from endemic areas of Brazil. We
      conclude that children are indeed more susceptible to VL when they are younger
      and more malnourished, but it remains unclear whether the immunity to VL acquired
      with age is always acquired as a result of infection. The significance for
      leishmaniasis control, and for the control of other diseases associated with
      malnutrition, will depend on underlying mechanisms, which are not yet understood.

PMID- 8265674
TI  - Energetic efficiency and ecology as selective factors in the saltatory adaptation
      of prosimian primates.
AB  - We tend to assume that natural selection will bring about 'optimal'
      configurations in morphology and behaviour. Jumping locomotion involves large
      forces and energy costs which, in this non-cyclic activity, are generated anew
      with each jump. Jumping appears to be, therefore, a major target for
      optimization. It has been a standard assumption that jumpers will tend to adopt
      ballistic paths which will minimize the energy costs involved in jumping, and
      will act to minimize the loads applied to the body. Experimental studies, using
      kinematic analysis of digitized video recordings of the jump in five prosimian
      primates, with a 25-fold range in body mass, show that most do not adopt energy
      efficient paths until the length of the jump is close to the maximum they can
      attain. Statistical analysis of quantified field observations suggests that, of
      three primate jumpers, only the largest, most unspecialized appears to take the
      forces applied to the musculoskeletal system into consideration when selecting
      supports used in locomotion. 'Ecological' factors, such as time pressure and
      habitat support density, may thus be the prime consideration for many species in
      determining the manner in which they jump.

PMID- 8265675
TI  - Principal component analysis learning algorithms: a neurobiological analysis.
AB  - The biological relevance of principal component analysis (PCA) learning
      algorithms is addressed by: (i) describing a plausible biological mechanism which
      accounts for the changes in synaptic efficacy implicit in Oja's 'Subspace'
      algorithm (Int. J. neural Syst. 1, 61 (1989)); and (ii) establishing a potential
      role for PCA-like mechanisms in the development of functional segregation. PCA
      learning algorithms comprise an associative Hebbian term and a decay term which
      interact to find the principal patterns of correlations in the inputs shared by a
      group of units. We propose that the presynaptic component of this decay could be
      regulated by retrograde signals that are translocated from the terminal arbors of
      presynaptic neurons to their cell bodies. This proposal is based on reported
      studies of structural plasticity in the nervous system. By using simulations we
      demonstrate that PCA-like mechanisms can eliminate afferent connections whose
      signals are unrelated to the prevalent pattern of afferent activity. This
      elimination may be instrumental in refining extrinsic cortico-cortical
      connections that underlie functional segregation.

PMID- 8265676
TI  - Generation and propagation of ectopic beats induced by spatially localized Na-K
      pump inhibition in atrial network models.
AB  - A biophysically detailed two-dimensional network model of the cardiac atrium has
      been implemented on the Thinking Machines massively parallel CM-5 supercomputer.
      The model is used to study the effects of spatially localized inhibition of the
      Na-K pump. Na overloading produced by pump inhibition can induce spontaneous,
      propagating ectopic beats within the network. At a cell-to-cell coupling value
      yielding a realistic plane wave conduction velocity of 0.6 m s-1, pump inhibition
      in roughly 1000 cells can induce propagating ectopic beats in a 512 x 512 lattice
      of cells.

PMID- 8265677
TI  - Comparative evidence indicating neural specialization for predatory behaviour in
      mammals.
AB  - The evolution of cognitive and sensory specializations must involve concomitant
      modifications of neural substrates. Ecological correlates of species differences
      in brain structure are intriguing sources of evidence about such evolutionary
      specialization but, to date, these have been identified only for gross
      parameters, such as overall brain size and the size of major brain regions. Here
      we show that a behavioural specialization in mammals, predation, is associated
      with species differences in the fine structure of a single neural pathway, the
      tectospinal tract. Both the relative number of neurons in this pathway and the
      relative size of their cell bodies were greater in more predatory species than in
      their less predatory counterparts within each of four separate mammalian orders.
      Expansion of these analyses to consider comparisons between taxa at a variety of
      taxonomic levels gave further support to the idea of a relation between predatory
      habits and the evolution of the tectospinal tract. In addition, within the
      primates, the number of neurons in the tectospinal tract was significantly
      correlated with the proportion of prey in the diet. These results therefore
      appear to provide an example of correlated evolution between a specific neural
      system and behaviour which applies generally within the mammals. They also help
      to unify findings from physiological and anatomical studies on a wider range of
      vertebrate taxa, including reptiles and amphibians.

PMID- 8265678
TI  - Parasite-associated polymorphism in a cyclic ungulate population.
AB  - An unmanaged population of Soay sheep living on Hirta, St Kilda, Scotland is
      persistently unstable, fluctuating between about 600 and 1600 individuals.
      Population crashes occurring approximately every 3 years are primarily due to
      winter food shortage. In this paper we show that sheep experimentally relieved of
      their gastrointestinal nematodes (predominantly Teladorsagia spp.) survived a
      crash better than matched controls, showing that nematode parasites contribute to
      the probability that a sheep dies in a crash. We also show that over three
      successive crashes mortality was significantly different between individuals of
      the three different genotypes at the diallelic adenosine deaminase locus (Ada).
      FF animals were most likely to die, SS animals had an intermediate probability of
      dying, and FS animals were least likely to die. Finally, three independent lines
      of evidence suggest that nematode burdens differ between the three Ada genotypes.
      First, in August, heterozygous females are less likely to have nematode eggs in
      their faeces than homozygous females. Second, at lambing, the periparturient rise
      in faecal egg count was highest in homozygous FF individuals. Finally, during the
      Autumn mating season, heterozygous males has lower faecal egg counts than
      homozygotes, although this relation was complicated by interactions with year and
      age of male. These results are consistent with the idea that Ada allele
      frequencies are maintained in the sheep population by parasite-associated
      selection.

PMID- 8265679
TI  - Rapid smoking of menthol and nonmenthol cigarettes by black and white smokers.
AB  - White subjects took significantly more puffs of cigarette smoke before stopping
      than did black subjects in a modified, controlled-dose rapid smoking procedure.
      Paradoxically, however, no racial differences were detected for changes in carbon
      monoxide levels, or changes in cardiovascular variables (systolic and diastolic
      blood pressure, and heart rate). Due to the cooling and topical anesthetic
      properties of menthol, it was hypothesized that menthol and regular cigarette
      smokers would take more puffs from menthol cigarettes than from regular
      cigarettes before stopping in the controlled-dose rapid smoking procedure.
      However, no difference was observed for the number of puffs taken from regular as
      opposed to menthol cigarettes (cigarette type condition) and no differences were
      found for Cigarette Preference (regular smokers vs. menthol smokers).

PMID- 8265680
TI  - Automated method for the measurement of fentanyl-induced muscular rigidity.
AB  - An automated method is described that can accurately and reliably measure weight
      displacement resulting from hindlimb extension due to muscular rigidity following
      opioid administration in rats. IV administration of fentanyl (0.035 mg/kg)
      immediately induced rigidity. Rigidity was dose dependently reversed by the alpha
      2-agonist clonidine with an ED50 value equal to 0.011 mg/kg IV. Second, rigidity
      was restored following administration of the alpha 2-antagonist idazoxan (0.3
      mg/kg, IV) thereby confirming an alpha 2-mediated mechanism of action.
      Previously, reversal of fentanyl-induced muscular rigidity was measured by
      subjective rating criteria not suitable for quantitative potency comparisons. The
      new automated rigidity model provides a simple yet precise measurement of the
      ability of alpha 2-agonists to attenuate opioid-induced muscular rigidity in
      rats.

PMID- 8265681
TI  - Antiepileptogenic action of 7-chlorokynurenic acid on amygdala kindling of rats.
AB  - To investigate the role of strychnine-insensitive glycine receptors in epilepsy,
      we studied the effects of 7-chlorokynurenic acid (7-CK), a selective strychnine
      insensitive glycine receptor antagonist, on amygdala kindling development and
      previously amygdala-kindled seizures in rats. ICV administration of 7-CK (10 or
      20 micrograms) suppressed amygdala kindling development, according to the motor
      seizure stage and afterdischarge development, in a dose-dependent manner.
      However, 7-CK had no significant effect on previously kindled seizures at either
      of these doses nor did 20 micrograms at any time (15 min, 30 min, 2 h, and 24 h)
      after injection studied. These results demonstrate that this selective strychnine
      insensitive glycine receptor antagonist has antiepileptogenic activity and
      suggest a role for the glycine receptors in the contribution of the NMDA receptor
      complex to epileptogenic events.

PMID- 8265682
TI  - Circadian variation in tolerance to the hypothermic action of CNS drugs.
AB  - Male SAF mice (30-35 g) or male Sprague-Dawley rats (180-250 g) were used to
      study the circadian variation in tolerance to the hypothermic action of ethanol,
      apomorphine, and nicotine. Animals were treated for 2 or 3 consecutive days
      during the light phase (1000, 1400, or 1800 h) or the dark phase (2200, 0200, or
      0600 h) and hypothermia produced measured. In one experiment, repeated injections
      of 20% ethanol (3 g/kg, IP) to mice resulted in varying degrees of hypothermia
      depending upon the time of injection. Tolerance to hypothermic action was
      observed only in animals treated during the light phase. On the contrary, the
      hypothermic response in animals treated during the dark phase increased. In
      another experiment, apomorphine (15 mg/kg, IP) was used and tolerance to
      apomorphine-induced hypothermia observed following repeated injections during the
      light phase with maximum tolerance noticed at 1400 h. In the third experiment,
      nicotine (2 mg/kg, IP) was repeatedly administered and resulted in tolerance
      development when given during the light phase. These results indicate that the
      rapid development of tolerance to CNS drugs studied is a diurnally controlled
      phenomenon.

PMID- 8265683
TI  - Pharmacological evaluation of iodo and nitro analogs of delta 8-THC and delta 9
      THC.
AB  - One aspect of cannabinoid structure-activity relationships (SARs) that has not
      been thoroughly investigated is the aromatic (A) ring. Although halogenation of
      the side chain enhances potency, our recent observation that iodination of the A
      ring also enhanced activity was surprising. The purpose of this investigation was
      to establish the steric and electrostatic requirements at these sites of the
      cannabinoid molecule via molecular modeling, while determining pharmacological
      activity. Molecular modeling was performed using the Tripos molecular mechanics
      force field and the semiempirical quantum mechanical package AM1. The Ki values
      for novel cannabinoids were determined in a [3H]CP-55,940 binding assay and ED50
      values generated from four different evaluations in a mouse model. The present
      studies underscore the increase in potency produced by a dimethylheptyl (DMH)
      side chain. Trifluoro substitutions on the pentyl side chain, or bromination of
      the DMH side chain, had little effect on the pharmacological activity. Any
      substitution at the C4 position of the aryl ring resulted in a loss of activity,
      which appears to be due to steric hindrances. Nitro, but not iodo, substitution
      at the C2 position essentially produces an inactive analog, and the drastic
      alteration of the electrostatic potential appears to be responsible. The altered
      pharmacological profile of the 2-iodo analog seems to be related to an alteration
      in the highest occupied molecular orbital because there is no alteration in the
      electron density map compared to delta 8-tetrahydrocannibinol.

PMID- 8265684
TI  - Nicotine potentiation of haloperidol-induced catalepsy: striatal mechanisms.
AB  - Nicotine potentiated the catalepsy produced by haloperidol. The excitotoxin
      quinolinic acid (QA) selectively destroys striatal neurons when injected directly
      into the striatum. Bilateral QA lesions of the rat striatum (150 nmol)
      significantly reduced the catalepsy produced by haloperidol as well as the
      ability of nicotine to potentiate haloperidol-induced catalepsy. A second
      experiment examined whether the ability of nicotine to potentiate haloperidol
      induced catalepsy was associated with a potentiation of dopamine turnover
      following haloperidol. Nicotine alone produced a mild increase in dopamine
      turnover relative to saline treated controls while haloperidol produced a marked
      increase in dopamine turnover relative to saline- and nicotine-treated controls.
      However, the combined administration of haloperidol and nicotine did not further
      elevate dopamine turnover over that observed following haloperidol alone. The
      results indicated that: 1) nicotine could not potentiate haloperidol-induced
      catalepsy without an intact striatum and 2) the behavioral effect of nicotine and
      haloperidol cotreatment was not due to any change in dopamine turnover.

PMID- 8265685
TI  - Decreased tolerance to ethanol-induced hypothermia in long-term castrate male
      rats.
AB  - A potential role for central stores of vasopressin in the development of
      tolerance was studied in the long-term castrate rat. Vasopressin stores in the
      septal region are known to be dramatically depressed following long-term
      castration. Sprague-Dawley male rat littermates were castrated at 26 days of age
      or given a sham surgery. Experiments began when animals reached 130 days of age.
      Tolerance to the hypothermic effects of ethanol occurred in intact but not
      castrate animals over the course of six daily IP injections of 3.0 g/kg ethanol.
      Both groups exhibited tolerance to the length of time needed to return to
      baseline temperature over the 6 days of ethanol injections. Tolerance to this
      effect of ethanol was still evident in intact animals but not castrates following
      another injection of ethanol 1 week later. No tolerance developed to the rebound
      hyperthermia that occurred in both groups. Blood ethanol levels did not differ
      significantly between castrate and intact littermates administered a single dose
      of ethanol. Overall, these results support the hypothesis that endogenous
      vasopressin is involved in the development of some aspects of tolerance to
      ethanol.

PMID- 8265686
TI  - Effect of stress on oral fentanyl consumption in rats in an operant self
      administration paradigm.
AB  - The effect of intermittent footshock stress (0.8 mA; 0.2 s on; 40 s off on the
      average; for 10 min/day) on oral fentanyl (50 or 75 micrograms/ml) self
      administration (SA) in operant chambers was examined in male rats. In Experiment
      1, after 1 month of initiation of the fentanyl SA by partial water deprivation,
      animals were tested for lever-pressing for fentanyl (75 micrograms/ml) under
      fixed-ratio-4 (FR-4) and progressive-ratio (PR) schedules of reinforcement for 30
      min/day in operant chambers. Exposure to footshock stress increased fentanyl SA
      under the FR-4 and PR schedules compared with a nonstress condition. When water
      was substituted for the drug, the operant behavior persisted before extinction.
      In Experiment 2, different rats were tested for lever-pressing for fentanyl (50
      micrograms/ml) under FR-6 and PR schedules. This experiment further assessed the
      role of taste in the stress-induced fentanyl SA and examined the effect of
      increasing the schedule requirements (i.e., FR-3, 6, and 12) on lever-pressing
      for fentanyl. Exposure to footshock stress increased lever-pressing for oral
      fentanyl SA under the FR schedules of reinforcement. When a quinine solution (30
      micrograms/ml), matched for bitter taste with the fentanyl solution, was
      substituted for the drug solution, an extinction of the drug-reinforced behavior
      occurred, indicating that the stress-induced oral fentanyl SA is not related to
      stress-induced changes in taste sensitivity. In both experiments, no significant
      stress effects were observed for water consumption in home cage and lever
      pressing on the nonoperative lever.

PMID- 8265687
TI  - Effects of haloperidol, lithium, and valproate on phosphoinositide turnover in
      rat brain.
AB  - The effects of acute, subacute, and chronic treatment with haloperidol, lithium,
      and valproate on inositol phosphate (IP) formation were examined. Acute treatment
      with haloperidol or the combination of haloperidol and lithium significantly
      reduced IP basal cortical levels. Subacute (three days) treatment with lithium
      decreased the IP basal level in the frontal cortex. Chronic treatment with
      haloperidol (14 and 28 days) caused a significant attenuation of carbachol
      sensitive IP accumulation in the frontal cortex and striatum and a significant
      decrease in norepinephrine (NE)-induced IP formation in the frontal cortex (14
      and 28 days) and striatum (28 days). Lithium treatment for 14 days produced a
      significant reduction in the IP basal cortical value, and a significant reduction
      in cortical carbachol- and NE-induced IP formation was found after 28 days of
      lithium treatment. The combination of haloperidol and lithium for 28 days
      decreased the striatal carbachol- and cortical NE-induced IP accumulation and
      caused a significant increase in NE-sensitive IP formation in the striatum at 14
      days. Valproate treatment for 28 days was associated with a significant
      attenuation in striatal agonist-stimulated IP formation. Therefore, three drugs
      with different specificities for primary neurotransmitters may have common
      effects on second-messenger systems.

PMID- 8265688
TI  - Dopamine release and metabolism in nucleus accumbens and striatum of morphine
      tolerant and nontolerant rats.
AB  - Morphine administered at high doses produces a biphasic locomotor effect,
      characterized by an initial locomotor depression, followed a short time later by
      hyperlocomotion. Prior exposure to morphine produces tolerance to the motor
      depressive effects and sensitization to the motor-activating effects of morphine.
      Little is known of the neurochemical changes that occur to produce tolerance and
      sensitization to morphine. In the present study, we developed a morphine
      pretreatment regimen in rats that produced both tolerance and sensitization to a
      high (30 mg/kg) dose of morphine. Using in vivo microdialysis, we then measured
      dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA)
      release in the nucleus accumbens (NAC) and striatum (STR) in morphine- and saline
      pretreated rats after acute morphine administration. In morphine
      tolerant/sensitized rats, basal DA concentrations in the NAC were higher and
      levels of DOPAC and HVA in the NAC after acute morphine injection were greater
      compared to controls. These results suggest that the NAC, but not the STR, may be
      important in mediating tolerance and sensitization to opiates.

PMID- 8265689
TI  - 5-HT and carbohydrate suppression: effects of 5-HT antagonists on the action of d
      fenfluramine and DOI.
AB  - The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists on the
      anorectic effect of d-fenfluramine and the 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy
      4-iodophenyl)-2-aminopropane (DOI) were examined in a dietary paradigm that
      appears to be sensitive to 5-HT-induced carbohydrate suppression. In this
      paradigm, deprived rats are provided with a nutritionally complete hydrated chow
      mash diet together with an optional carbohydrate supplement of powdered Polycose.
      Both d-fenfluramine and DOI produced a clear suppression of total energy intake
      and carbohydrate (Polycose) intake. However, the mechanisms underlying these
      effects are different. The effect of d-fenfluramine in this paradigm was
      attenuated by the 5-HT1/5-HT2 receptor antagonist metergoline and partially
      attenuated by the 5-HT1A/5-HT1B receptor antagonist (+/-)cyanopindolol. In
      contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor
      antagonist ketanserin, the 5-HT3 receptor antagonist (3 alpha-tropanyl)-1H-indole
      3-carboxylic acid ester (ICS-205,930), the 5-HT2/5-HT1C receptor antagonist
      ritanserin, or the peripheral 5-HT receptor antagonist xylamidine. However, the
      effect of DOI in this paradigm was significantly attenuated by ketanserin but was
      not antagonised by either ritanserin or (+/-)cyanopindolol. Therefore, the
      suppressive effect of these two 5-HT drugs on total and Polycose intake appears
      to be mediated, respectively, by 5-HT1B/5-HT1C receptors (d-fenfluramine) and 5
      HT2 receptors (DOI).

PMID- 8265690
TI  - Analgesic effects of antibiotics in rats.
AB  - Studies in forelimb-deafferented rats suggest that treatment with certain
      antibiotics can decrease pain sensation. To test this hypothesis, the analgesic
      effects of nine randomly selected antibiotics were studied in rats by using a
      constant-temperature hotplate. The results show that several antibiotics have
      antinociceptive properties, and two of them, chloramphenicol and ampicillin, can
      produce analgesia in a dose range used in human therapy (100 mg/kg). This
      analgesia is comparable to salicylate and ketoprofen analgesia but lower than
      pethidine's one. The analgesia is long lasting with chloramphenicol (10 h or
      more). These antinociceptive properties cannot be attributed to sedation because
      amphetamine-induced hyperactivity, measured in an open field, is not sensitive to
      injection of the most sensitive antibiotics.

PMID- 8265691
TI  - Reduction of spontaneous alcohol drinking and physical withdrawal by levemopamil,
      a novel Ca2+ channel antagonist, in rats.
AB  - Neuronal Ca2+ channels have been shown to be involved in both alcohol drinking
      behavior in rats and nonhuman primates and in the manifestation of alcohol
      withdrawal symptoms in rodents. Experiments were performed to determine the
      effect of a single injection of levemopamil, a novel Ca2+ channel antagonist with
      antiserotonergic [5-hydroxytryptamine2 (5-HT2)] properties, on alcohol preference
      and alcohol withdrawal symptoms in alcohol-preferring (P) and Wistar rats,
      respectively. P rats were individually housed and provided free access to food,
      water, and a solution of 10% (v/v) ethanol. Ethanol, food, and water intakes were
      measured daily. After establishing a stable baseline, P rats were injected with
      levemopamil (0, 3.3, 10, 15, and 20 mg/kg) and their food, water, and alcohol
      intakes measured 24 h later. In a separate experiment, the ability of acute and
      chronic (12 consecutive days) administrations of levemopamil to suppress alcohol
      withdrawal symptoms in chronically alcohol-treated rats was studied. In addition,
      the effects of levemopamil on the level of monoamines in different areas of the
      brain, as well as its action in alcohol metabolism, were examined. Our findings
      showed that a single administration of levemopamil (10, 15, and 20 mg/kg)
      significantly and dose-dependently attenuated alcohol intake and increased water
      intake in P rats. Both acute and chronic treatment with levemopamil reduced the
      alcohol withdrawal symptoms, overall seizure scores, and proportion of rats
      seizing. A single injection of levemopamil produced a clear, but not significant,
      trend to increase the 5-HT turnover rate in certain brain areas. This drug did
      not influence the pharmacokinetics of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265692
TI  - A developmental study on stress-induced antinociception measured by the tail
      electric stimulation test.
AB  - The possible influence of weaning on the development of different neural
      mechanisms involved in stress-induced antinociception (SIA) was studied. Male
      Wistar albino rats were used for studies on adult and pre- and postweanling rats
      of 20 and 25 days of age, respectively. Animals were stressed by warm-water (20C)
      swimming for 3-min periods. Antinociception was assessed by the tail electric
      stimulation test. The thresholds for the motor response (tail withdrawal) (TW),
      vocalization during stimulus (V), and vocalization after discharge (VAD) were
      recorded. These responses are considered to be integrated at spinal, medulla
      oblongata, and diencephalon-rhinencephalon levels, respectively. In 20-day-old
      neonates, swimming stress only induced significant increases in the VAD
      thresholds that were not significantly reversed by naloxone (NAL) (1 mg/kg).
      Twenty-five-day-old rats showed increased threshold for the three nociceptive
      responses after stress, the effects on TW and V being antagonized by NAL. Adult
      rats subjected to stress showed increased threshold for the three responses, an
      effect that was antagonized by NAL in all cases. These results suggest that the
      weaning period might be critical for the development of the mechanisms mediating
      SIA. Besides, a different involvement of opioid systems throughout development,
      particularly in relation to the affective/emotional component of pain, is also
      suggested.

PMID- 8265693
TI  - Modulation of dopamine binding in the fetal rat: effects of milk and exogenous
      opioid manipulation.
AB  - Presentation of milk to the newborn rat promotes changes in sensory and motor
      behavior and concomitant changes in both endogenous opioid and dopamine systems.
      The present study employed an in vivo binding technique with a tritiated ligand
      for the D2 receptor ([3H]raclopride) to examine the effects of intraoral milk
      infusion and opioid manipulations on dopamine activity in the term rat fetus
      (E21). In Experiment 1, fetuses received a series of milk infusion, which
      resulted in decreased occupancy at D2 receptors by the endogenous ligand,
      dopamine, in striatal, septal, and hypothalamic brain regions. In Experiment 2,
      fetuses were pretreated with morphine, the mu-agonist [D-Ala2,NMe-Phe4,Gly5-ol]
      enkephalin (DAMGO), the kappa-agonist U50,488, or saline. Opioid manipulations
      had no effect on binding at D2 receptors. These results confirm that intraoral
      milk infusion can modulate activity in the dopamine system of the near-term fetal
      rat.

PMID- 8265694
TI  - Behavioral effects of the mu-opioid peptide agonists DAMGO, DALDA, and PL017 on
      locomotor activities.
AB  - The relative role of central mu-opioid receptor agonists Tyr-D-Ala-Gly-N-Methyl
      Phe-Gly-ol (DAMGO), Tyr-D-Arg-Phe-Lys (DALDA), and Tyr-Pro-MePhe-D-Pro (PL017)
      (0.00, 0.01, 01, or 1.0 micrograms, ICV) on behavior was investigated in rats for
      60 min in activity monitors. DAMGO (0.1 and 1.0 micrograms) and PL017 (1.0
      micrograms) resulted in biphasic effects, inhibition followed by hyperactivity
      for linear locomotor, whereas the 0.01-micrograms dosage was associated with
      hyperactivity. On the other hand, DALDA (0.1 and 1.0 micrograms) suppressed
      locomotor activity over the 60-min session.

PMID- 8265695
TI  - Effects of acute haloperidol and reserpine administration on vacuous jaw
      movements in three different age groups of rats.
AB  - In these experiments three different age groups of rats were tested for vacuous
      jaw movements. The age groups included rats aged 3 months, rats aged 6-9 months,
      and rats aged 12-15 months. In the first experiment, rats were given a single IP
      injection of either 0.3% tartaric acid vehicle or 0.4 mg/kg haloperidol. In the
      second experiment, rats were given injections of vehicle or 5.0 mg/kg reserpine.
      Haloperidol and reserpine significantly increased vacuous jaw movements. There
      were significant effects of age on vacuous jaw movements, with rats aged 6-9
      months and rats aged 12-15 months showing more jaw movements than 3-month-old
      rats. In both experiments, the drug x age interaction was not significant,
      indicating that the combined effects of age and neuroleptic treatment were
      additive and not synergistic. Haloperidol and reserpine also reduced rearing
      behavior in all age groups. It is concluded that age is an important variable in
      studies of vacuous jaw movements.

PMID- 8265696
TI  - Comparison between phenylpropanolamine and structurally related compounds on
      gastric transit in the rat.
AB  - Our laboratory previously reported several pharmacological differences between
      phenylpropanolamine [PPA; (+/-)-norephedrine] and its structurally related
      compounds in regard to their activity on cardiovascular and appetite-suppressant
      parameters. The present study investigates the pharmacological differences
      between PPA, [1R,2R]-(-)-norephedrine [(-)-NOR], [1S,2S]-(+)-norephedrine [(+)
      NOR], [1R,2S]-(-)-ephedrine [(-)-EPH], [1S,2R]-(+)-ephedrine [(+)-EPH], [1R,2S]-(
      )-norpseudoephedrine [(-)-NORP], [1S,2R]-(+)-norpseudoephedrine [(+)-NORP],
      [1R,2R]-(-)-pseudoephedrine [(-)-PSE], and [1S,2S]-(+)-pseudoephedrine [(+)-PSE],
      as determined by their ability to inhibit gastric transit in the rat. (-)
      Norephedrine was approximately three times more potent in inhibiting gastric
      transit than (+)-NOR (p < 0.01). As anticipated, the racemic mixture, PPA,
      demonstrated an ED50 (25.1 mg/kg) of approximately the mean of the ED50s from the
      component enantiomers (14.7 and 47.0 mg/kg, respectively). Similarly,
      administration of 20 mg/kg of either (-)-EPH, (+)-EPH, (-)-PSE, or (+)-PSE
      significantly decreased gastric transit by 26% (p < 0.001), 12% (p < 0.01), 10%
      (p < 0.01), and 11% (p < 0.01), respectively. Administration of (-)-NORP and (+)
      NORP were without effect. These data confirm and extend previous findings
      demonstrating pharmacological differences between PPA and its structurally
      related compounds.

PMID- 8265697
TI  - Effects of idebenone on information processing in aged Long-Evans rats.
AB  - Idebenone (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone) is a
      benzoquinone that has been shown to improve cognitive function in animals
      subjected to cerebral ischemia and in rats with lesions of the basal forebrain
      cholinergic system. Because the cognitive deficits observed in aged rats have
      been associated with decreased cerebral blood flow and basal forebrain
      cholinergic dysfunction, it was hypothesized that IDE might improve cognition in
      aged animals. In the present study, the effects of idebenone on cognitive
      function in aged Long-Evans rats were assessed using a battery of tests that
      evaluated attention, habituation, and spatial learning. Selective attention was
      assessed using an overshadowing paradigm, where IDE (30 mg/kg, IP) was injected
      30 min prior to compound cue exposure. IDE enhanced the overshadowing effect in
      aged rats. The Morris water maze was used to assess spatial learning, where IDE
      (3 mg/kg, IP) was injected daily throughout the course of training. IDE did not
      improve the impaired performance of aged rats in the Morris task. Habituation was
      tested by measuring recovery from gustatory neophobia. IDE (30 mg/kg, IP) was
      injected 30 min prior to the first exposure to the novel taste. IDE normalized
      habituation rate in aged rats. It was concluded that IDE improves some forms of
      acquisition in aged rats, and may do so by decreasing general reactivity to novel
      stimuli.

PMID- 8265698
TI  - Modulation of oral movements by intranigral 5-hydroxytryptamine receptor agonists
      in the rat.
AB  - Bilateral infusion of 5-hydroxytryptamine (5-HT) agonists into the substantia
      nigra pars reticulata (SNr) of awake rats was shown to influence oral behavior.
      The 5-HT1A agonist (R)-8-hydroxy-2-(di-propylamino)- tetralin (8-OH-DPAT) (1.3-13
      nmol on each side) produced a dose-dependent depression of vacuous chewing
      movements (VCMs) that lasted about 20 min. The (R)-8-OH-DPAT-induced depression
      of VCMs was blocked by the simultaneous intranigral infusion of a specific 5-HT1A
      antagonist [(-)-(S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin HCl (UH-301)],
      which had no effect when given alone. Another 5-HT1A agonist [(5-methoxy-N,N
      dimethyltryptamine hydrogen oxalate (5-MeO-DMT)] also reduced VCM frequencies.
      Intranigral infusion of the nonspecific 5-HT-agonists 1-(3-triflouro
      methylphenyl) piperazine (TFMPP) and 1(m-chlorophenyl)-piperazine (mCPP) and a 5
      HT3 agonist [2-methyl-5-hydroxytryptamine (2-Me-5-HT)] increased VCM after 5- to
      10-nmol doses. Another 5-HT3 agonist (1-phenylbiguanide) and a 5-HT2 agonist [1
      (4-bromophenyl-2,5-dimethoxy)-2-aminopropane (DOB)] had no significant effect. As
      most 5-HT receptors in the SNr are of the 5-HT1B subtype, these results suggest
      that the increased VCM frequency was mediated via nigral 5-HT1B receptors. The
      importance of 5-HTergic mechanisms in the development of drug-induced dyskinesias
      is discussed.

PMID- 8265699
TI  - Titrating matching-to-sample performance in pigeons: effects of diazepam,
      morphine, and cholinergic agents.
AB  - Five adult, male White Carneau pigeons were trained to respond under a titrating
      matching-to-sample schedule of reinforcement. Under this titration schedule, each
      trial began with the presentation of a sample stimulus (red or green light) on
      the center key of a three-key pigeon chamber. Completion of 15 responses on the
      center key resulted in the termination of the stimulus presentation and the
      initiation of a delay period. The length of the delay changed as a function of
      the pigeon's performance. During the first five trials of each session, the delay
      was fixed at 3 s in length. On the sixth and all subsequent trials, the length of
      the delay was either increased, did not change, or decreased such that accuracy
      was maintained at approximately 80%. Following the delay, two of the three pigeon
      keys were transilluminated with different colored lights (red or green). A single
      response upon the key transilluminated with the same stimulus color as the sample
      stimulus resulted in the presentation of food. A response on the key
      transilluminated with the stimulus color that did not match the sample stimulus
      resulted in a time-out period. Using this procedure, the effects of two drugs of
      abuse, diazepam (0.03-3 mg/kg) and morphine (0.03-10 mg/kg), a muscarinic
      antagonist, scopolamine (0.003-0.3 mg/kg), the quaternary derivative of
      scopolamine, methylscopolamine (0.003-0.3 mg/kg), a cholinesterase inhibitor,
      physostigmine (0.003-0.1 mg/kg), and the quaternary derivative of physostigmine,
      neostigmine (0.003-0.1 mg/kg), were determined. Diazepam decreased matching
      accuracy such that a decrease in the mean delay value for the session was
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265700
TI  - Acute and chronic stressor effects on the antibody response to sheep red blood
      cells.
AB  - Exposure to inescapable foot-shock 72 h following immunization with sheep red
      blood cells resulted in a marked suppression of the peak splenic immunoglobulin
      (Ig)M plaque-forming cell response and plasma antibody titers in CD-1 mice.
      However, the nature of this effect was influenced by the animal's stressor
      history. In particular, if mice were initially exposed to a single stressor
      session immediately or 24 h following antigen treatment subsequent reexposure to
      the stressor (72 h following inoculation) did not provoke the immunosuppression.
      Moreover, reexposure to the stressor-related cues elicited a marked
      immunoenhancement. In contrast, if animals were exposed to a single stressor
      session 48 h prior to inoculation then later reexposure to the stressor-related
      cues provoked an immunosuppression. Among mice that had been exposed to a
      repeated stressor regimen on successive days prior to inoculation, the
      immunosuppression ordinarily elicited by an acute stressor was absent. Indeed,
      chronic stressor exposure typically favored potentiation of the immune response.
      However, the immunofacilitation elicited by the chronic stressor treatment likely
      was unrelated to the immunoenhancing effects of pairing a stressor with antigenic
      challenge.

PMID- 8265702
TI  - Antagonistic effects of caffeine and alcohol on mental performance parameters.
AB  - Scientific experiments done so far allow no clear conclusions about the popular
      belief that freshly brewed coffee can offset the debilitating effects of
      alcoholic intoxication. This question was addressed using a computer-controlled
      and subject-paced rapid information processing task (RIP) which was shown earlier
      to be sensitive to psychoactive substances. Nine male students were tested in a
      Latin square design before and after the intake of 3.3 mg/kg caffeine (or
      placebo) followed by 0.7 g/kg alcohol (or placebo). Whereas the mean RIP-task
      processing rate and the mean reaction time were impaired by alcohol and improved
      by caffeine, no changes were observed after the combination of alcohol and
      caffeine. Thus, it was concluded that under the tested conditions, caffeine was
      able to offset the debilitating effects of alcohol.

PMID- 8265701
TI  - Nicotine and brain-stimulation reward: interactions with morphine, amphetamine
      and pimozide.
AB  - Using a rate-independent discrete trial method of determining thresholds for
      rewarding electrical intracranial stimulation in rats, we evaluated the
      pharmacological interaction of nicotine plus morphine, d-amphetamine, or the D2
      receptor antagonist, pimozide. Both morphine and amphetamine shifted the dose
      response curve for nicotine down and to the left, indicating increased efficacy
      and potency, respectively. Pimozide at doses that have no effect on performance
      and only minimal effect on brain-stimulation reward blocked the effect of
      nicotine. These data suggest that the same dopaminergic substrate that supports
      the positive reinforcing effects of other drugs of abuse also supports nicotine
      reward.

PMID- 8265703
TI  - Opioidergic manipulations affect intake of 3% NaCl in sodium-deficient rats.
AB  - On six weekly occasions, a 3% NaCl solution was presented along with water to
      rats for 2 h 1 day after being treated with furosemide, a diuretic/natriuretic
      drug that causes a strong hunger for 3% NaCl. On some of the days, the sodium
      hungry rats were injected with morphine in doses ranging from 0.3 to 10.0 mg/kg.
      Morphine produced biphasic effects on intake of 3% NaCl, with doses of 0.3-3.0
      mg/kg increasing intakes dose dependently and 10.0 mg/kg decreasing intakes. The
      3.0-mg/kg dose nearly doubled rats' mean intake of 3% NaCl. In contrast,
      naltrexone, an opioid receptor antagonist, reduced intake of 3% NaCl about 25-40%
      across doses ranging from 0.1 to 10.0 mg/kg. At some doses of morphine and
      naltrexone, NaCl ingestion was affected without significant influence of water
      intake. Therefore, it can be inferred that endogenous opioidergic systems
      participate in the control of NaCl drinking by sodium-deficient rats. The range
      of demonstrations of opioid involvement in the control of ingestion can now be
      extended to the hunger for hypertonic NaCl induced by sodium depletion.

PMID- 8265704
TI  - Ethanol differentially affects extracellular monoamines and GABA in the nucleus
      accumbens.
AB  - The magnitude, direction, and time course of the effects of acute administration
      of ethanol (0.1 or 1.0 g/kg) on the extracellular levels of dopamine (DA),
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine
      (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), and GABA within the nucleus
      accumbens of the rat were analysed using microdialysis in conjunction with high
      pressure liquid chromatography and electrochemical detection. IP injection of 0.1
      g/kg ethanol failed to modify the extracellular concentration of DA, DOPAC, HVA,
      5-HT, 5-HIAA, and GABA in the nucleus accumbens during the 120-min collection
      period. On the contrary, 1.0 g/kg IP ethanol significantly increased
      extracellular levels of DA, DOPAC, and 5-HIAA in microdialysates from the nucleus
      accumbens. The maximal increase in DA (314.87 +/- 6%), DOPAC (210.58 +/- 3%), and
      5-HIAA (250.88 +/- 8%) was observed 40 min after administration of ethanol.
      Extracellular HVA was also enhanced (220.89 +/- 2%) at time point 100 min
      following injection of the same dose of ethanol. Finally, extracellular levels of
      5-HT and GABA remained unchanged following 1.0 g/kg ethanol.

PMID- 8265705
TI  - Saccharin effects on morphine-induced temperature change in rats.
AB  - The effects of saccharin on morphine-induced temperature change was examined in
      Long-Evans rats. Rats were given free access to 0.15% saccharin for 15 days,
      followed by saccharin deprivation for 9 days. Saccharin was then returned to one
      group, while a second group received water. All rats were then injected with
      morphine sulfate (2 mg/kg), and postinjection temperatures were assessed over 75
      min. The results showed that saccharin enhanced the biphasic effects of morphine
      by significantly increasing the hypothermic phase. The findings support the view
      that sweet substances influence endogenous opioid release.

PMID- 8265706
TI  - Injecting 5-HT into the PVN does not prevent feeding induced by injecting 8-OH
      DPAT into the raphe.
AB  - The selective 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OH-DPAT) activates raphe somatodendritic autoreceptors,
      leading to an inhibition of 5-HT neuronal activity and reduced synthesis and
      release of 5-HT in forebrain terminal areas. One behavioural consequence of this
      is increased feeding in satiated rats. Because injections of 5-HT agonists into
      the medial hypothalamus suppress feeding, it has been proposed that 8-OH-DPAT
      induced feeding may involve a reduction of 5-HT release within this area. This
      hypothesis was tested by examining the ability of 5-HT injected into the medial
      hypothalamus to reverse the feeding-stimulant action of 8-OH-DPAT following
      injection into the dorsal raphe or median raphe. Two groups of rats, maintained
      with free access to food at all times, were used. Each was prepared with two
      cannulae, one aimed at the paraventricular nucleus (PVN) of the medial
      hypothalamus and the other at either the dorsal raphe nucleus or median raphe
      nucleus. Food intake over the next hour was increased following dorsal raphe or
      median raphe injections of 8-OH-DPAT (1 and 0.5 microgram, respectively). These
      effects were not blocked by injections of 7.5 or 15 micrograms 5-HT into the PVN.
      However, 15 micrograms 5-HT did attenuate the feeding-stimulant action of 10
      micrograms norepinephrine injected into the PVN. These results do not support the
      hypothesis that a reduction in 5-HT release within the medial hypothalamus is
      responsible for the feeding-stimulant action of 8-OH-DPAT.

PMID- 8265707
TI  - [Interactions between food ingredients and drugs].

PMID- 8265708
TI  - Vermiculin derivatives. Part 1: Synthesis of vermiculin derivatives.
AB  - Hydrogenation of the macrodiolide antibiotic vermiculin (1) over Adams catalyst
      afforded [8S, 16S]-8,16-bis(2'-oxopropyl)-1,9- dioxyacyclohexadeca-2,5,10,13
      tetrone (2), [8S, 16S]-8,16-bis(2'-oxopropyl)-13-hydroxy-1,9-dioxacyclohexadeca-
      2,5,10-trione (3), [8S,16S]-8,16-bis(2' oxopropyl)-1,9- dioxacyclohexadeca-2,5,10
      trione (4) together with [7S]-4,9-dioxo-7-(4',9'-dioxodecanoyloxy)decanoic acid
      (5). Hydrogenation of diolide 1 over Pd/C gave tetrahydrovermiculin (2) only. The
      prepared compounds showed lower antibacterial and cytotoxic activities than
      vermiculin (1).

PMID- 8265709
TI  - [The solubility of drugs in lipoid vehicles].
AB  - A method for determination of drug substances solubility in lipophilic solvents
      is presented. The solubility was determined in lipophilic suppository bases
      meltings, in pharmaceutical lipoids as Oleum Ricini, Oleum Arachidis, Cera
      perliquida, Paraffinum perliquidum and in chemically defined lipoids as n
      hexadecane, 1-hexadecane, cetylic alcohol, palmitic acid, cetylpalmitate.
      Consequences from chemical constitution of substances for solubility are
      discussed, also consequences from chemical constitution and dielectric constants
      of lipoidic solvents for their solution behavior. For the substances
      investigated, the apparent partition coefficients in the two-phase systems
      lipoid/phosphate buffer pH 7,4 and n-octanol/phosphate buffer pH 7,4 were
      determined, also the solubility in phosphate buffer. The results show, that
      connections between partition coefficients and solubility in lipophilic or
      aqueous phases do not exist. On the other hand, an indirect proportionality
      between water solubility and lipoid solubility also does not exist. In
      consequence, interpretations of drug release from lipophilic systems have to be
      proceeded from exact knowledge of partition behavior and solubilities in both the
      lipophilic and aqueous phase.

PMID- 8265710
TI  - Conventional versus novel conditions for the in vitro dissolution testing of
      parenteral slow release formulations: application to doxepin parenteral dosage
      forms.
AB  - Parenteral slow release formulations of doxepin in lipid vehicles were prepared
      in the form of suspensions of doxepin hydrochloride, doxepin pamoate and of poly
      D,L-lactid and poly D,L-lactid-co-glycolide microspheres containing doxepin
      hydrochloride. The drug particles or the drug containing microspheres were
      suspended in the vehicles isopropylmyristate or Miglyol. The dissolution rate of
      the different doxepin formulations was investigated in two flow through cells, a
      membrane and a non-membrane system, using either plain buffer or human plasma
      containing buffer as dissolution media, in order to study the influence of
      dissolution conditions on dissolution rates. An attempt was made to obtain
      biorelevant dissolution data. In the membrane system a linear relationship
      between time and percent drug dissolved during the period of investigation was
      found. Drug release was very slow and incomplete, especially when buffer was used
      as dissolution medium. Dissolution data from the nonmembrane system were fitted
      to monoexponential and biexponential models, respectively. Significant
      differences were found using different modes of formulation positioning and using
      the two dissolution media. The most rapid release rates were found when the
      formulations were spread on glass carriers and plasma was used as dissolution
      medium. It is suggested that this dissolution procedure has physiological
      relevance.

PMID- 8265711
TI  - Biochemical, structural and ultrastructural changes in the Prague hereditary
      hypercholesterolemic (PHHC) rats heart after the long treatment with calcium
      channel blockers.
AB  - Elevated plasma cholesterol concentration may be important in the initiation of
      heart ischemia and progression of atherogenesis. It has been shown that drugs
      affecting calcium entry into cells can attenuate the development of this
      cholesterol induced changes. The aim of this work was to study the influence of
      five calcium channel blockers 6 weeks treatment on some parameters of lipid
      metabolism, morphological and ultrastructural changes in the Prague hereditary
      hypercholesterolemic (PHHC) rats myocardium. The calcium antagonists were
      administered twice daily perorally in the following doses: nifedipine and
      nitrendipine 0.2 mg.kg-1, nimodipine 2.5 mg.kg-1, verapamil and diltiazem 1.0
      mg.kg-1 body weight. Cholesterol diet decreased the level of free fatty acids
      significantly (from 5.59 +/- 0.216 to 3.83 +/- 0.371 mumol.g-1), increased the
      level of total cholesterol (from 28.0 +/- 1.92 to 34.0 +/- 2.90 mumol.g-1) and
      caused micronecrosis. Examination of myocardial ultrastructure showed a frequent
      occurrence of lysosomes as well as large numerous autophagic vacuoles and
      contracture bands of myofibrils. These effects were partly suppressed by calcium
      channel blockers verapamil and diltiazem, but dihydropyridines were not
      effective. Observed biochemical changes were in accordance with structural and
      ultrastructural investigations.

PMID- 8265712
TI  - Protection by alpha-tocopherol against skin necrosis induced by doxorubicin
      hydrochloride.
AB  - Extravasation of doxorubicin hydrochloride during i.v. infusions can cause
      serious local complications due to the action of free radicals which are produced
      as a result of this leakage. An experiment was carried out using female Wistar
      rats to study the protective effect of alpha-tocopherol against the tissular
      necrosis produced by 0.05 mg of doxorubicin hydrochloride. alpha-Tocopherol was
      administered by two vehicles, one emulsified and the other gelled, with butylated
      hydroxytoluene and ascorbic acid used as antioxidants, respectively. No
      differences were observed in the diameters of the ulcers with each treatment in
      the various groups of animals relative to the control group. Conversely,
      differences were found (p < 0.05) in the period of chronic lesion between the
      animals treated with alpha-tocopherol and those used as a control group,
      irrespective of the vehicle used. These results lead to the conclusion that
      accidental toxicity resulting from the leakage of doxorubicin hydrochloride in
      the skin can be mitigated by applying alpha-tocopherol topically, due to its
      regenerating action in the damaged cutaneous zones. This effect is independent of
      the vehicle used and also of the antioxidant employed in the elaboration of the
      formulas.

PMID- 8265713
TI  - New 2-thioxo-4,5-imidazolidinedione derivatives as possible anticonvulsants.

PMID- 8265714
TI  - New 4-arylhydrazono-5(4H)-isoxazolone derivatives as possible antibacterial and
      anticonvulsant agents.

PMID- 8265715
TI  - In vivo evaluation of polyisobutylcyanoacrylate microparticles containing
      fluorouracil.

PMID- 8265716
TI  - Antibacterial activity of propolis, some of its components and their analogs.

PMID- 8265717
TI  - Stimulation of Coleus blumei Benth. callus growth by 1-(6-purinyl)-2,5
      dimethylpyrrole.

PMID- 8265718
TI  - Functional consequence of big endothelin conversion: demonstration with isolated
      neutrophils but not in a postinfarction model.
AB  - The role of neutrophils in the conversion of big endothelin (Big-ET) to
      endothelin-1 (ET-1) was assessed in two models. In rabbit isolated hearts, ET-1
      demonstrated significant increases in coronary perfusion pressure (PP) at doses
      greater than 100 pmol. With Big-ET, significant increases were obtained only at
      doses greater than 3 nmol. Similarly, this dose of Big-ET did not increase PP in
      isolated, perfused hearts from rabbits previously subjected to 60 min of coronary
      artery occlusion and 4 h of reperfusion (n = 7). However, when isolated rabbit
      neutrophils were incubated with Big-ET (n = 5) or vehicle (n = 4) and 3 nmol
      aliquots assayed in isolated hearts, results demonstrated a time-dependent
      conversion to a vasoactive product. These findings suggest that isolated
      neutrophils are capable of converting Big-ET to an ET-1-like vasoactive
      substance. The model may be useful in assessing antagonists of endothelin
      converting enzyme activity and/or the endothelin receptor.

PMID- 8265719
TI  - Effect of hyperkalemia on myocardial depression by verapamil in isolated hearts.
AB  - Verapamil can produce depression of left ventricular function, delayed
      atrioventricular conduction, and hypotension, which can be potentiated by
      hyperkalemia. We sought to investigate a direct cardiac interaction between
      verapamil and hyperkalemia. Studies utilized isolated guinea pig hearts
      (Langendorff) paced at 250 beats/min. Hearts were randomly assigned to perfusion
      (Krebs-Henseleit buffer) with potassium concentrations ([K]+) of 1.5, 3, 6 and 9
      mmol/l. Infusion of verapamil at rates of 0.2 to 60 micrograms/min (approximately
      3 x 10(-8) to 10(-5) mol/l) produced concentration-dependent reduction of
      isovolumic left ventricular developed pressure. As [K]+ increased, concentration
      response curves showed parallel shifts to the left. The ED50 for reduction of
      left ventricular developed pressure significantly decreased: 8.2 +/- 3.7, 2.9 +/-
      1.4, 1.2 +/- 0.7, 0.6 +/- 0.2 micrograms/min (mean +/- SD), respectively.
      Nifedipine and diltiazem were also studied in hearts perfused with 3 and 9 nmol/l
      [K]+. Infusion of nifedipine 0.003-1 microgram/min (approximately 10(-9) to 3 x
      10(-7) mol/l) produced concentration-dependent reduction of left ventricular
      developed pressure but the ED50 was not affected by [K]+: 0.06 +/- 0.03 and 0.05
      +/- 0.04 microgram/min, respectively. Nifedipine vehicle was without effect at
      the infusion rates tested. Infusion of diltiazem 2-200 micrograms/min
      (approximately 3 x 10(-7) to 3 x 10(-5) mol/l) also produced concentration
      dependent reduction of left ventricular developed pressure. The ED50 for
      diltiazem-induced reduction of left ventricular developed pressure was
      significantly reduced by elevated [K]+: 20.1 +/- 6.7 and 3.5 +/- 0.9
      micrograms/min with 3 and 9 mmol/l [K]+, respectively.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8265720
TI  - Suppression of intestinal smooth muscle contraction by 4-ethylguaiacol, a
      constituent of wood creosote.
AB  - Wood creosote, a mixture of phenolic compounds, suppresses in vitro contractions
      of rat intestine. To identify a compound in wood creosote able to inhibit
      intestinal motility, we screened its constituent phenolic compounds and found 4
      ethylguaiacol (4-EG) as an active compound. It suppressed the spontaneous phasic
      (IC50 = 513 +/- 48 mumol/l) as well as spasmogenic-agent-induced tonic
      longitudinal contractions of isolated rat ileum in a reversible and concentration
      dependent manner. KCl-depolarization-induced tonic contraction, which was
      susceptible to a calcium channel blocking agent, was also suppressed by 4-EG with
      an IC50 of 433 +/- 41 mumol/l. Furthermore, calcium-ionophore-induced
      contraction, which was affected by an influx of extracellular calcium ion that
      bypassed calcium channels, was suppressed by 4-EG with an IC50 of 97 +/- 18
      mumol/l. These results support the concept that the effect of wood creosote to
      suppress intestinal motility is attributable, partially or entirely, to its
      component 4-EG and that this effect of 4-EG on the intestinal muscle is produced
      at some stage(s) of the muscle contraction process after influx of extracellular
      calcium into the cytosol of smooth muscle.

PMID- 8265721
TI  - Pharmacokinetics and irreversible binding of tolmetin and its glucuronic acid
      esters in the elderly.
AB  - In a previous study, the disposition and irreversible plasma protein binding of
      tolmetin have been described in young volunteers. Significant levels of tolmetin
      glucuronide and its isomer(s) were found in plasma, and irreversible binding was
      shown to occur in all subjects. In the present study, the pharmacokinetics and
      irreversible binding in 5 elderly volunteers are investigated after a single dose
      (400 mg) of tolmetin. No difference of physiological importance has been found,
      unless weight correction is employed, when compared with the young subjects. Very
      strong correlations were present between the level of binding and exposure to the
      glucuronide or its isomer. An elderly patient currently treated with tolmetin
      (400 mg b.i.d.) also participated in the study. The results show an accumulation
      of the irreversible binding to levels 4-17 times higher than after a single dose.
      Nevertheless, neither toxic nor allergic reactions have been observed in this
      patient.

PMID- 8265722
TI  - Tin-mesoporphyrin inhibits heme oxygenase activity and heme-iron absorption in
      the intestine.
AB  - Long-term treatment with the heme oxygenase inhibitor tin-mesoporphyrin produces
      an iron deficiency anemia in rats analogous to that we reported in patients with
      the Crigler-Najjar type I syndrome receiving prolonged treatment with the
      inhibitor to ameliorate severe jaundice [Pediatrics 1992; 89: 175-182]. A dose-
      and time-dependent inhibition of intestinal heme oxygenase is produced by tin
      mesoporphyrin which is independent of iron status of the animal. Tin
      mesoporphyrin inhibits the intestinal enzyme whether administered orally or
      parenterally. Enzyme inhibition by either route results in diminished uptake of
      59Fe from radiolabelled heme in the gut. Since tin-mesoporphyrin stimulates
      excretion of unmetabolized heme into bile its ability to inhibit intestinal heme
      oxygenase and to decrease heme-iron absorption in the gut probably accounts in
      part for the iron deficiency produced by the agent. The availability of an orally
      active agent which inhibits heme oxygenase and heme-iron absorption in the
      intestine may prove useful for experimental and therapeutic studies in diseases
      of iron metabolism.

PMID- 8265723
TI  - Cookbooks and aphorisms.

PMID- 8265724
TI  - Local sensation changes and altered hip muscle function following severe ankle
      sprain.
AB  - BACKGROUND AND PURPOSE: Changes in sensory information have been shown to
      influence muscle function locally. Some clinicians, however, believe that the
      influence may be more extensive. To investigate this clinical concept, subjects
      with severe ankle sprain were assessed for local sensation changes and proximal
      hip/back muscle function. SUBJECTS: Of a total of 361 potential subjects whose
      medical histories were assessed, 20 men (age 18-35 years) who had previously
      sustained a severe unilateral ankle sprain and 11 matched "control" subjects with
      no previous lower-limb injury participated in the study. METHODS: Using this
      experimental model, tests of vibration sensation in the ankle (indicating
      sensation changes) as well as surface electromyography of muscle recruitment
      patterns for hip extension (indicating muscle function proximally) of the biceps
      femoris, gluteus maximus, and lumbar erector spinae muscles were made on both
      sides of the unilaterally injured and matched control subjects. RESULTS:
      Significant decreases in vibration perception and significant delays in gluteus
      maximus muscle recruitment during hip extension were found in the injured group.
      CONCLUSION AND DISCUSSION: The author concludes that both local sensory and
      proximal muscle function changes are associated with unilateral severe ankle
      sprain.

PMID- 8265725
TI  - Are incentive spirometry, intermittent positive pressure breathing, and deep
      breathing exercises effective in the prevention of postoperative pulmonary
      complications after upper abdominal surgery? A systematic overview and meta
      analysis.
AB  - BACKGROUND AND PURPOSE: The purpose of this meta-analysis was to quantitatively
      assess the conflicting body of literature concerning the efficacy of incentive
      spirometry (IS), intermittent positive pressure breathing (IPPB), and deep
      breathing exercises (DBEX) in the prevention of postoperative pulmonary
      complications in patients undergoing upper abdominal surgery. METHODS:
      Computerized searches of MEDLINE and the Cumulative Index to Nursing and Allied
      Health databases were performed for the years 1966 through 1992. Citations were
      selected based on the following relevance criteria: (1) patients undergoing any
      type of upper abdominal surgery; (2) any combination of IS, IPPB, and DBEX; (3)
      an outcome of pulmonary complications; and (4) randomized trials. Review of 116
      citations yielded 55 potential trials and 10 review articles. Of these, 14
      citations were included in the overview based on relevance criteria requirements.
      Study validity was assessed by two independent observers, and data were
      extracted. RESULTS: The common odds ratio (COR) for the occurrence of pulmonary
      complications for IS versus no physical therapy was 0.44 in favor of IS. The COR
      for DBEX versus no physical therapy was 0.43 in favor of DBEX. Both findings were
      statistically significant. The CORs for IS versus IPPB, IS versus DBEX, and IPPB
      versus DBEX were 0.76 (95% confidence interval [CI] = 0.39-1.4), 0.91 (95% CI =
      0.57-1.4), and 0.94 (95% CI = 0.28-3.17), respectively. None of these comparisons
      reached statistical significance. CONCLUSION AND DISCUSSION: Incentive spirometry
      and DBEX appear to be more effective than no physical therapy intervention in the
      prevention of postoperative pulmonary complications. There is no evidence to
      support a significant difference between any of the three modalities. [Thomas JA,
      McIntosh JM. Are incentive spirometry, intermittent positive pressure breathing,
      and deep breathing exercises effective in the prevention of postoperative
      pulmonary complications after upper abdominal surgery? a systematic overview and
      meta-analysis.

PMID- 8265726
TI  - Radiologically observed progression of joint destruction and its relationship
      with demographic factors, disease severity, and exercise frequency in patients
      with rheumatoid arthritis.
AB  - BACKGROUND AND PURPOSE: The aim of the study was to investigate the 4-year
      progression of radiologically observed joint destruction and its relationship
      with demographic factors, disease severity, and exercise frequency in patients
      with rheumatoid arthritis. SUBJECTS: The subjects were 69 patients (56 women, 13
      men; mean age = 54 years; mean duration of symptoms = 14 years) with American
      Rheumatism Association functional class II rheumatoid arthritis. METHODS: The
      patients were assessed with a modified Larsen's radiological index (maximum score
      = 220), laboratory tests, Ritchie's articular index, and questionnaires regarding
      their self-selected low-intensive-intensive dynamic exercise frequency. RESULTS:
      The Larsen's radiological index was initially 67 (SD = 42.4) and progressed to 82
      (SD = 42.3) during the 4-year study period. Four-year radiological progression
      correlated with mean erythrocyte sedimentation rate (30 mm/h, SD = 12.6), but not
      with self-selected exercise frequency (< or = once a week or > or = twice a week)
      or with any other variables investigated. CONCLUSION AND DISCUSSION: The
      radiologically observed progression of joint destruction seemed rather slow in
      this group of nonhospitalized, functionally independent patients with rheumatoid
      arthritis, and it was only related with mean erythrocyte sedimentation rate. Self
      selected exercise frequency did not seem to be related with radiologically
      observed progression of joint destruction.

PMID- 8265727
TI  - A review of the principles of pulse oximetry and accuracy of pulse oximeter
      estimates during exercise.
AB  - This article reviews the principles of pulse oximetry and assesses the accuracy
      of pulse oximeter measurements obtained during exercise, based on reports of 10
      studies that evaluated 24 pulse oximeters. Nine of the studies used cycle
      exercise, and 1 study utilized treadmill running for mode of activity. Subject
      populations included patients with cardiovascular or pulmonary disorders,
      nondisabled individuals, and athletes. Studies were performed under normoxic and
      hypoxic conditions, and 5 of the 10 studies validated 18 pulse oximeters at
      arterial oxyhemoglobin saturation (%HbO2) levels of < or = 78%. Sixteen of the 24
      pulse oximeters (67%), from 7 of the 10 studies, observed pulse oximeter
      estimates (%SpO2) during exercise to be accurate, at least when %HbO2 was > or =
      85% in nonsmokers. However, the degree of accuracy of the pulse oximeters was
      variable, even among the same models. Recent studies suggest the current
      generation of finger-probe-equipped pulse oximeters may be more accurate than ear
      probe-equipped models. We recommend that clinicians carefully secure the probe;
      monitor signal strength; be wary of %SpO2 values of < or = 68% to 78% to avoid
      undetected severe hypoxemia; and be alert to whether a patient is a smoker, in
      which case %SpO2 will likely be overestimated. Researchers interested in using
      pulse oximeter estimates should validate their particular pulse oximeter(s) via
      arterial blood sampling.

PMID- 8265728
TI  - Muscle atrophy and procedures for training after spinal cord injury.
AB  - Functional electrical stimulation (FES) of paralyzed muscles holds promise as a
      strategy to assist patients in executing functional movements after spinal cord
      injuries. Muscle atrophy is one of the major problems that must be addressed for
      this approach to be successful. Loss of muscle mass may occur as a result of
      lesions to motoneurons in either the spinal cord or the central command pathway,
      or a combination of the two. For injuries to spinal motoneurons, muscle fibers
      undergo denervation atrophy. Damage to the central command pathway, on the other
      hand, results in disuse atrophy. In association with atrophy, the low contractile
      forces and inability of the muscles to sustain contractions are of direct
      therapeutic concern. In this review, methods aimed at recovery of function of
      paralyzed limbs by reducing susceptibility to fatigue and atrophy of paralyzed
      muscles are discussed. One is related to promoting nerve sprouting in partially
      denervated muscles to reinnervate muscle fibers and reverse denervation atrophy.
      The other regards training of paralyzed muscles to increase strength (muscle
      force) and endurance (fatigue resistance) by means of FES. Most training regimens
      with low-frequency FES increase muscle endurance. Efforts to design optimal
      regimens for increasing both muscle strength and endurance must involve
      consideration of several factors that are still controversial. These factors,
      which include muscle properties (such as fiber type composition and physiological
      type) and conditions imposed on the muscle (such as loading) during contractions
      elicited by FES, are discussed in detail.

PMID- 8265729
TI  - Motor unit behavior in Parkinson's disease.
AB  - This article reviews the literature related to motor unit behavior in Parkinson's
      disease (PD). The focus is on bradykinesia, or slowed movement. There is sparse
      literature on muscular performance in PD, as PD is regarded as a disease of
      higher motor centers. Nevertheless, a decrease in muscle activation has been
      demonstrated, and motor unit behavior is altered so that (1) the discharge
      patterns of motor units are irregular and intermittent, (2) a greater number of
      motor units are recruited at low thresholds as compared with the findings for age
      matched control subjects, and (3) antagonist muscles are abnormally coactivated.
      Possible reasons for these changes include imbalances in excitatory and
      inhibitory inputs to motor neurons, adaptations in motor neurons secondary to
      disuse, or deviations in the normal aging process. For the physical therapy of
      persons with PD, we propose a greater emphasis on strength-training exercises.

PMID- 8265730
TI  - Effects of age and training on skeletal muscle physiology and performance.
AB  - Aging skeletal muscle exhibits decreases in muscle mass and force and changes in
      contractile properties. The effects of aging on the physiological characteristics
      of skeletal muscle are fiber type specific. This review describes the aging
      process in skeletal muscle; specifically, the effects of aging on the
      biochemical, morphological, and physiological characteristics of type I (slow
      twitch) fibers and type II (fast-twitch) fibers. The effects of training on
      specific fiber types are also reviewed. The age-related decrease in maximum
      isometric force may be due, in part, to a decline in muscle mass. Decreases in
      muscle mass appear to occur in weight-bearing muscles and are most marked in
      those with a high proportion of type II fibers. The age-related fiber atrophy
      contributes to the decline in muscle mass. The decline in fiber size is prominent
      in type II fibers, whereas type I fibers are less affected. The age-related
      prolongation in isometric twitch properties may be due, in part, to alteration in
      the capacity of the sarcoplasmic reticulum for calcium release and recapture.
      Resistance and endurance training appear to attenuate the age-related alterations
      in skeletal muscle properties if the stimulus is of a sufficient intensity and
      duration.

PMID- 8265731
TI  - [New diagnostic criteria for psychiatric diseases].

PMID- 8265732
TI  - [Basic and clinical study of senile dementia].

PMID- 8265733
TI  - [Short-term memory functioning in schizophrenics--late components (P3) of the
      event-related potential recorded from schizophrenics during a memory retrieval
      task].
AB  - Event-related potentials were measured in 14 schizophrenic patients and age
      matched 14 normal control subjects during a Sternberg's memory-scanning paradigm.
      The stimuli used were digits presented visually. In this paradigm each set of
      stimuli was presented for memorization (memory set), while varying the number of
      items (1, 2, 4) in each set, and following the mask stimulus, a probe item (test
      stimulus) appeared and was identified by the subject as belonging or not
      belonging to the memory set. Reaction times (RT) and performance accuracy were
      computed and ERPs to the test stimuli were recorded for each memory set size and
      response type. As P3 peaks in some schizophrenic patients were rather ambiguous,
      instead of using the conventional peak-picking method, P3 latency was determined
      from single trials using an adaptive correlating filter (ACF) technique, and P3
      amplitude was measured from the latency-adjusted averages to reduce the jittering
      effect. For the behavioral measures, significant difference was not obtained
      between the groups. Though P3 latency increased and amplitude decreased as a
      function of memory set size for the normal controls, by contrast, neither latency
      nor amplitude of P3 was not influenced by memory set size for schizophrenics.
      Moreover, schizophrenic patients had smaller single trial P3 latency/RT
      correlations compared to normal controls. Applying the two memory-load dependent
      processes by Lewine, which are memory strength-evaluation and serial search
      stage, impaired ability of rehearsing or allocating attentional resource to each
      item, producing an increase in the strengths of their representations in the
      working memory, was suggested for schizophrenics. Accordingly, serial search
      process was hardly undertaken by schizophrenics, at least before response
      determination.

PMID- 8265734
TI  - The dexamethasone suppression test in genetically different rats exposed to
      inescapable and escapable electric shocks.
AB  - The Dexamethasone Suppression Test (DST) was applied to male rats of Koltushi
      high- (KHA) and low-avoidance (KLA) strains, genetically selected on the basis of
      divergent acquisition of a conditioned avoidance response in a two-way
      shuttlebox. Rats were exposed to either inescapable (IS) or escapable (ES)
      electroshock. IS produced escape deficit in a shuttle box only in KHA rats. ES
      enhanced escape failures only in KLA rats. There were no differences in plasma
      corticosterone levels between naive KLA and KHA rats. IS led to increase of the
      post-dexamethasone corticosterone levels in KHA rats, while both basal and stress
      induced corticosterone levels in the KHA strain remained unchanged following IS.
      In KLA rats exposed to IS, both pre- and post-dexamethasone basal corticosterone
      levels were increased and stress-induced corticosterone levels were decreased.
      Thus, resistance to the DST after IS occurred only in KHA rats. ES led to
      enhanced basal and reduced stress-induced corticosterone levels in KLA rats
      compared to KHA rats before and after dexamethasone treatment. These findings
      suggest that the HPA axis reactivity following aversive stimuli depends on the
      interaction between genotype and stressor controllability.

PMID- 8265735
TI  - Growth hormone response to growth hormone-releasing hormone in early abstinent
      alcoholic patients.
AB  - The alpha-2-adrenoceptor agonist clonidine is able to stimulate GHRH secretion
      directly or via beta-endorphin and, therefore, induces a GH release in normal
      subjects. This effect has been shown to be blunted in alcoholism during early
      abstinence, due to central alterations of adrenergic mechanisms. To evaluate
      pituitary responsiveness to direct stimulation with GHRH, we have studied the GH
      and PRL response to GHRH in 10 alcoholics during early abstinence. Our data
      indicate that the pituitary response to GHRH is intact in abstinent alcoholics,
      except in obese patients, who displayed a blunted GH response. GHRH did not
      increase PRL. The dissociation between clonidine and GHRH in GH stimulation could
      reveal a different neuroendocrine mechanism, in comparison with other psychiatric
      disorders (anorexia nervosa), in which such a dissociation is accompanied by a
      PRL response to GHRH.

PMID- 8265736
TI  - Maternal separation in neonatal rats elicits activation of the hypothalamic
      pituitary-adrenocortical axis: a putative role for corticotropin-releasing
      factor.
AB  - Stress elicits activation of the hypothalamic-pituitary-adrenocortical (HPA)
      axis. Hypothalamic neurohormones, including corticotropin-releasing factor (CRF),
      control and promote ACTH secretion and subsequent glucocorticoid synthesis and
      release. The neonatal rat has been shown to be relatively hyporesponsive to
      certain stressors, generating a blunted or unmeasurable hormonal response. In
      this study, the endocrine response of 10- and 18-day-old Sprague-Dawley rat pups
      to maternal separation, a naturalistic stressor, was examined. Ten-day pups
      subjected to maternal separation exhibited a significant reduction in median
      eminence CRF concentration at 24 h, with no change in pituitary CRF receptor
      number; in 18-day pups there was no significant change in median eminence CRF
      concentration by 24 h, but there was a decrease in CRF receptor binding. In adult
      rats subjected to stressors, an acute decrease in CRF concentration in the median
      eminence occurs, followed by CRF receptor downregulation with sustained stress.
      The results observed in the 18-day pups vs. the 10-day pups likely reflects a
      maturation of the HPA axis response to "stressors."

PMID- 8265737
TI  - Blockade of pituitary-adrenal axis activation induced by peripheral
      immunoneutralization of corticotropin-releasing factor does not affect the
      behavioral response to social defeat stress in rats.
AB  - Specific in vivo immunoneutralization of hypophysiotrophic corticotropin
      releasing factor (CRF) and vasopressin (AVP) was used to investigate the
      respective roles of these circulating peptides in the hormonal response to a
      social stressor in Wistar rats. The effect of peripheral immunoneutralization on
      the behavioral response to the same social stressor was also studied. Stress was
      produced using social defeat in a resident-intruder paradigm, in which an
      intruder male rat, equipped with an indwelling IV catheter, was confronted with a
      dominant resident male rat. To minimize the physical component of the agonistic
      interaction, the intruder was protected immediately after the resident's first
      attack in a Plexiglas/wire-mesh enclosure. In the following time interval, the
      resident continued to threaten the protected intruder, which showed a significant
      increase in plasma immunoreactive adrenocorticotropic hormone (ACTH) and
      corticosterone levels compared to those measured in rats exposed to a control
      procedure. The hypothalamo-pituitary-adrenal (HPA) axis response to social defeat
      stress was totally abolished by pretreatment with an anti-CRF serum (0.3 ml IV)
      but not an anti-AVP serum (0.75 ml IV). An animal model for anxiety in rodents,
      the elevated plus-maze, was used to study the emotional response to social defeat
      stress in rats given anti-CRF serum or normal serum. A significant reduction of
      open-arm exploration was observed in defeated rats tested 10 min after the end of
      the agonistic interaction when compared with control animals for all antisera
      treatment group, indicating an "anxiogenic-like" emotional response to the social
      defeat stress. Pretreatment with anti-CRF serum did not affect the behavioral
      performance of defeated and control rats. These results suggest that: 1) social
      defeat stress produced an activation of the HPA axis in the rat which is mediated
      by hypophysiotrophic CRF but not AVP; and 2) the peripheral activation of the HPA
      axis induced by social defeat stress is not involved in the behavioral response
      to stress as measured in the elevated plus-maze.

PMID- 8265738
TI  - No difference in cognitive performance between phases of the menstrual cycle.
AB  - No differences were seen in performance on either verbosequential or visuospatial
      neuropsychological tests among three groups of women. There were also no
      differences among the phases of the menstrual cycle on any of the tests. The
      design of this study was to sample performance of women on verbosequential and
      visuospatial neuropsychological tests during phases of the normal menstrual cycle
      in regularly menstruating women, and at comparable time points among women taking
      oral contraceptives and among those who had amenorrhea. Serum luteinizing hormone
      (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone were
      assayed to document these hormone levels at each time point for each group. These
      data are consistent with previous results in our laboratory but conflict with
      other reports in which shifts in cognitive function were related to fluctuations
      in estrogen. The only indications of positive results were weak correlations with
      gonadotropins and cognitive function across subjects. While some of these
      correlations replicated previous results, they were weak and should be considered
      with caution.

PMID- 8265739
TI  - A critical review of menstrual synchrony research.

PMID- 8265740
TI  - Negative behavior during marital conflict is associated with immunological down
      regulation.
AB  - Although increased morbidity and mortality have been reliably associated with
      social isolation and less satisfying personal relationships, relatively little is
      known about the underlying biopsychosocial mechanisms. We assessed problem
      solving behaviors and changes in immune function in 90 newlywed couples who were
      admitted to a hospital research unit for 24 hours. Subjects who exhibited more
      negative or hostile behaviors during a 30-minute discussion of marital problems
      showed greater decrements over 24 hours relative to low negative subjects on four
      functional immunological assays (natural killer cell lysis, blastogenic response
      to two mitogens, and the proliferative response to a monoclonal antibody to the
      T3 receptor), as well as larger increases in the numbers of total T lymphocytes
      and helper T lymphocytes. High negative subjects had higher antibody titers to
      latent Epstein-Barr virus than low negative subjects, consistent with down
      regulated immune function. Women were more likely to show negative immunological
      changes than men. The discussion of marital problems also led to larger increases
      in blood pressure that remained elevated longer in high negative subjects than
      low negative subjects. Positive or supportive problem-solving behaviors were not
      related to either immunological or blood pressure changes. These physiological
      differences were particularly noteworthy because marital satisfaction was high in
      both groups, and couples had been selected on the basis of stringent mental and
      physical health criteria. These data provide additional support for the link
      between personal relationships and immune function.

PMID- 8265741
TI  - Marital interaction--the context for psychosomatic research.

PMID- 8265742
TI  - Psychophysiology of the posttraumatic stress disorder: from sulfur fumes to
      behavioral genetics.
AB  - Neurophysiological hypotheses regarding the body-mind relationship in stress
      disorders have been formulated more than 300 years ago. In 1941 Abraham Kardiner
      ascribed the name "physioneurosis" to the condition known today as posttraumatic
      stress disorder (PTSD). Psychophysiological studies of PTSD started with the
      demonstration of increased responsiveness to external stimuli reminiscent of the
      traumatic event. Later, abnormal responses to mental imagery were studied, and
      these studies have resulted in new tools for the assessment and diagnosis of the
      disorder. Recent studies focus on responses to elementary stimulation, such as
      the auditory startle reflex, thereby exploring basic CNS routines of habituation
      and stimulus-discrimination. This article reviews the rapidly expanding
      literature on the psychophysiology of PTSD. Special emphasis is given to recent
      studies of the auditory startle and to their implications for the neurobiology of
      PTSD.

PMID- 8265743
TI  - A perspective and future dreams of PTSD as a psychosomatic disorder.

PMID- 8265744
TI  - Psychosocial predictors of mortality in 83 women with premature acute myocardial
      infarction.
AB  - This was an exploratory investigation of psychosocial risk factors for mortality
      in women with premature acute myocardial infarction (AMI). Subjects were 83
      female participants in the Recurrent Coronary Prevention Project, who were
      between the ages of 30 and 63 in 1978, nonsmoking, nondiabetic, and at least 6
      months beyond their index AMI. Follow-up ranged from 8 to 10 years, with an
      average of 8.5 years. Six deaths occurred in the 83 women over the follow-up.
      Univariate predictors of these deaths were arrhythmias on ECG (RR = 7.83, p =
      .003), being divorced (RR = 6.9, p = .003), being employed without a college
      degree (RR = 6.8, p = .03), and the inverse of Type A behavior, time urgency, and
      emotional arousability (p = .03; .005; .006, respectively). Multivariate stepwise
      logistic regression analysis produced a solution that included as independent
      predictors: arrhythmias on ECG (RR = 4.01, p = .004), being divorced (RR = 3.43,
      p = .01), and the inverse of time urgency (RR = 0.35, p = .02). In the
      multivariate model, "divorced" was interchangeable with "employed without a
      college degree" and "time urgency" was interchangeable with "emotional
      arousability." This small sample precludes firm conclusions, but provides a basis
      for hypothesis development.

PMID- 8265745
TI  - Social isolation, depression, and heart disease: research on women broadens the
      agenda.

PMID- 8265746
TI  - Testosterone and pubertal development as predictors of sexual activity: a panel
      analysis of adolescent males.
AB  - Strong cross-sectional relationships between testosterone (T) and sexual activity
      have been found for human adolescent males, even when level of pubertal
      development is controlled; however, it has not been demonstrated that sexual
      behavior increases over time as a consequence of hormonal changes. The purpose of
      this paper was to extend previous cross-sectional findings by demonstrating that
      sexual behavior is initiated and increases within individuals over time as a
      direct function of changes in T levels, rather than indirectly through pubertal
      development. Analyses are based on a 3-year panel study of about 100 7th- and 8th
      grade adolescent boys. Pubertal development and changes in pubertal development
      were significantly and positively related to changes in sexual ideation,
      noncoital behavior, and to the transition to sexual intercourse. Testosterone
      levels at study entry were significantly related to coital status at Time 1 and
      also predicted the transition to nonvirgin status. However, changes in hormone
      levels during the 3 years of study participation did not predict changes in
      ideation or noncoital sexual activity, regardless of the period of change or the
      lag time to effects. The panel data suggest, in contrast to earlier cross
      sectional results, that change in pubertal development is related to the
      initiation of sexual activity because of its social stimulus value, and not
      solely because it is determined by, or is a proxy for, changing hormone levels.
      Possible causes of the different findings in the cross-sectional and panel data
      are examined, and the implications and meaning of hormone/behavior relationships
      based on single measures are discussed.

PMID- 8265747
TI  - The promise of adrenergic receptor studies in psychophysiologic research II:
      Applications, limitations, and progress.
AB  - For years research in fields such as biologic psychiatry and hypertension has
      benefited from the use of receptor measures. It is only recently however, that
      investigators in the field of psychosomatic medicine have taken advantage of this
      methodology. Much of this research revolves around discerning the roles that
      adrenergic receptors play in stressful events and stress-related behaviors. Thus
      far, psychosomatic studies have focused primarily on three areas: 1) The effects
      of psychosocial stressors on adrenergic receptor function, 2) the relationship
      between adrenergic receptors and cardiovascular responses to stressors, and 3)
      the relationship between adrenergic receptor measures and coronary-prone
      behaviors. Although several important methodological issues need to be addressed,
      current studies are helping to decipher longstanding questions regarding the
      complex processes underlying behavior, stress, immunity, and the sympathetic
      nervous system. This paper reviews the progress and limitations of this research
      blossoming field.

PMID- 8265748
TI  - Endocrine correlates of sadness and elation.
AB  - In a series of three exploratory studies, we examined the endocrine correlates of
      elation and sadness produced by the Velten Mood Induction Procedure (VMIP). In
      Study 1, 10 college females participated in elation and sadness mood inductions
      on separate days. In Study 2, 12 college females participated in a neutral mood
      induction. In Study 3, 16 college-aged actresses participated in elation and
      sadness mood inductions as in Study 1. At regular intervals in each study, we
      assessed subjective ratings of emotions, serum cortisol and growth hormone, and
      heart rate and blood pressure. Results demonstrated that the VMIP induced the
      desired moods. Serum cortisol increased equally in response to both the sadness
      and elation mood inductions, but showed no change in response to the neutral mood
      induction. Select associations between affect and cortisol levels were also
      observed. Interestingly, our data from Study 3 also suggest that an association
      may exist between elation and growth hormone. These endocrine changes did not
      appear to be a function of general arousal as indexed by cardiovascular changes.
      We conclude that elation and sadness are associated with endocrine concomitants
      and that the VMIP is a viable method for examining such associations. These
      previously unreported affect-endocrine relationships are discussed and
      implications for psychobiological theories of emotion are considered.

PMID- 8265749
TI  - Positive states of mind and athletic injury risk.
AB  - Horowitz, Adler, and Kegeles recently developed the Positive States of Mind
      (PSOM) scale to assess the ability to achieve desirable states of mind. According
      to a stress and injury model, a theoretical foundation exists for the PSOM being
      used to predict vulnerability to athletic injuries. In the first study, 277
      collegiate athletes from 10 sports completed the PSOM. The scale showed good
      internal consistency; Cronbach's alpha was .77 for the six items. Principle
      components factor analysis revealed two distinct factors. No sex or ethnic
      differences occurred for the total PSOM scale or the two factors. In the second
      study, injury data were gathered throughout the season on 82 athletes who
      completed the PSOM. Pearson-product correlations revealed the factor, Focused on
      Task, significantly correlated with injury. Athletes able to attain higher
      positive states of mind were less at risk for injury. The studies indicate the
      acceptability of using the PSOM with an athletic population and its usefulness as
      a potential predictor of injury risk. Future research using the PSOM scale in
      more general injury and accident investigations is suggested.

PMID- 8265750
TI  - Toward improving the oral health of Americans: an overview of oral health status,
      resources, and care delivery. Oral Health Coordinating Committee, Public Health
      Service.
AB  - Dental and oral diseases may well be the most prevalent and preventable
      conditions affecting Americans. More than 50 percent of U.S. children, 96 percent
      of employed U.S. adults, and 99.5 percent of Americans 65 years and older have
      experienced dental caries (also called cavities). Millions of Americans suffer
      from periodontal diseases and other oral conditions, and more than 17 million
      Americans, including 10 million Americans 65 years or older, have lost all of
      their teeth. Preventive dental services are known to be effective in preventing
      and controlling dental diseases. Unfortunately, groups at highest risk for
      disease--the poor and minorities--have lower rates of using dental care than the
      U.S. average. Cost is the principal barrier to dental care for many Americans. Of
      the $38.7 billion spent for dental services in 1992, public programs, including
      Medicaid, paid for less than 4 percent of dental expenditures. More than 90
      percent of care was paid for either out-of-pocket by dental consumers or through
      private dental insurance. Americans are at risk for other oral health problems as
      well. Oropharyngeal cancer strikes approximately 30,000 Americans each year and
      results in an estimated 8,000 deaths annually. Underlying medical or handicapping
      conditions, ranging from rare genetic diseases to more common chronic diseases,
      affect millions of Americans and can lead to oral health problems. Among persons
      with compromised immune systems, oral diseases and conditions can have a
      significant impact on health. Oral diseases and conditions, though nearly
      universal, can be prevented easily and controlled at reasonable cost. Prevention
      and early, regular primary dental care are the best strategies to improve the
      oral health and quality of life of all Americans.

PMID- 8265751
TI  - Sexually transmitted diseases among young heterosexual urban adults.
AB  - A self-administered, confidential survey of respondents' history of selected
      sexually transmitted disease (STD) was conducted in 1987-88 among adults enrolled
      in a multicenter study of cardiovascular disease. Respondents (and response
      rates) included 535 white men (78 percent), 694 white women (89 percent), 262
      black men (48 percent), and 472 black women (64 percent), ages 21 to 40 years at
      the time of the survey. Among those who were heterosexually active, 43 percent of
      black women, 37 percent of black men, 33 percent of white women, and 21 percent
      of white men reported ever having had at least one STD in the survey. A history
      of syphilis or gonorrhea was more commonly reported by blacks than whites; a
      history of genital herpes, chlamydia, or genital warts was more commonly reported
      by women than men. Independent risk factors for having had at least one STD in
      the survey included female sex; use of cocaine, amphetamines, or opiates; and
      lifetime number of sex partners. The number of sex partners was the most
      predictive risk factor. Black race was a significant marker for other,
      unidentified STD risk factors. The data show a high prevalence of a lifetime
      history of STD among young heterosexual urban U.S. adults with possible
      implications for the future spread of human immunodeficiency virus infection.

PMID- 8265752
TI  - Factors influencing first intercourse for teenage men.
AB  - Analyses of a nationally representative survey of 1,880 15- to 19-year-old men
      were conducted to examine factors associated with (a) the age when first sexual
      intercourse occurred and (b) whether a condom or other contraceptive method was
      used at first intercourse. Discrete time-event history models assessed factors
      influencing their age until first intercourse. Black males began sexual activity
      significantly earlier than white or Hispanic males. Males who had been held back
      in school also began sexual activity earlier. If a respondent's mother had been a
      teenager when she first gave birth, or if his mother was employed during his
      childhood, he was more likely to initiate intercourse early. A variety of
      combinations of AIDS and sex education topics were examined for their association
      with one's age at the time of first intercourse: two topics were associated with
      earlier intercourse, and one was associated with delays in first intercourse.
      Logistic regression models examined correlates of using a condom or any effective
      male or female method of contraception at first intercourse: having received
      education about birth control was marginally associated with increased
      probability of using a condom or any effective male or female contraceptive
      method at first intercourse. These findings indicate the relevance of integrated
      approaches to school-based sex and AIDS education in delaying intercourse and
      promoting use of contraceptive methods.

PMID- 8265753
TI  - The impact of critical events of the 1980s on core functions for a selected group
      of local health departments.
AB  - Directors of 14 public health departments were surveyed for their perceptions on
      the impact of 20 critical events of the 1980s on public health performance. The
      departments were selected in 1979 from among those that were highly regarded by
      public health experts for exemplary performance, especially with regard to
      personal health services. The departments were the subjects of intensive case
      studies in 1979, 1983, and again in 1992. The public health functions that were
      most benefited in the 1980s were assessment and policy development. The assurance
      function was equivocally affected. Greatest positive impact was exerted by the
      acquired immunodeficiency syndrome-human immunodeficiency virus epidemic, by
      increase in fee income, and by the Institute of Medicine report, "The Future of
      Public Health." Negative influences, especially on the assurance function were
      exerted by loss of Federal grants, demographic changes, substance abuse, and
      economic downturn. Other critical events had equivocal or idiosyncratic effects.
      Analysis of public health practice according to the functions of assessment,
      policy development, and assurance appears to have utility for purposes of
      evaluation and planning.

PMID- 8265754
TI  - The use of scenario analysis in local public health departments: alternative
      futures for strategic planning.
AB  - Scenario analysis is a strategic planning technique used to describe and evaluate
      an organization's external environment. A methodology for conducting scenario
      analysis using the Jefferson County Department of Health and the national, State,
      and county issues confronting it is outlined. Key health care and organizational
      issues were identified using published sources, focus groups, questionnaires, and
      personal interviews. The most important of these issues were selected by asking
      health department managers to evaluate the issues according to their probability
      of occurrence and likely impact on the health department. The high-probability,
      high-impact issues formed the basis for developing scenario logics that
      constitute the story line holding the scenario together. The results were a set
      of plausible scenarios that aided in strategic planning, encouraged strategic
      thinking among managers, eliminated or reduced surprise about environmental
      changes, and improved managerial discussion and communication.

PMID- 8265755
TI  - Health status indicators for the year 2000: projections for Allegheny County,
      Pennsylvania.
AB  - A consensus set of health status indicators was released in July 1991 by the
      Centers for Disease Control and Prevention for use by public health officials at
      the Federal, State, and local levels in identifying and monitoring issues of
      public health importance. These health status indicators have been projected for
      the Year 2000 in Allegheny County, PA, with linear regression analyses of
      historical data. Indications are that mortality rates for black infants, breast
      cancer mortality, suicide, lung cancer mortality, incidence of acquired
      immunodeficiency syndrome, and the number of measles cases likely will not meet
      the year 2000 targets in Allegheny County. These data will prove useful in
      monitoring progress towards the year 2000 objectives and provide comparative data
      for other geographic areas of the United States with similar demographic
      characteristics.

PMID- 8265756
TI  - Advertising health: the case for counter-ads.
AB  - Public service advertisements have been used by many in hopes of "selling" good
      health behaviors. But selling good behavior--even if it could be done more
      effectively--is not the best goal for using mass media to prevent health
      problems. Personal behavior is only part of what determines health status. Social
      conditions and the physical environment are important determinants of health that
      are usually ignored by health promotion advertising. Public service advertising
      may be doing more harm than good if it is diverting attention from more effective
      socially based health promotion strategies. Counter-ads are one communications
      strategy that could be used to promote a broader responsibility for rectifying
      health problems. In the tradition of advocacy advertising directly promoting
      policy rather than products, counter-ads promote views consistent with a public
      health perspective. Counter-ads set the agenda for health issues, conferring
      status on policy-oriented strategies for addressing health problems. The primary
      purpose of counter-ads is to challenge the dominant view that public health
      problems reflect personal health habits. They are controversial because they
      place health issues in a social and political context. Advertising strategies for
      health promotion range over a spectrum from individually oriented public service
      advertising to socially oriented counter-advertising. The recent anti-tobacco
      campaign from the California Department of Health Services represents
      advertisements across the spectrum. Counter-ads that focus on a politically
      controversial definition for health problems are an appropriate and necessary
      alternative to public service advertising.

PMID- 8265757
TI  - Joseph W. Mountin, architect of modern public health.

PMID- 8265758
TI  - The seroprevalence of cysticercosis, malaria, and Trypanosoma cruzi among North
      Carolina migrant farmworkers.
AB  - A seroprevalence study of cysticercosis, Trypanosoma cruzi, and plasmodia species
      and screening for active malaria was conducted among a randomly selected group of
      138 Hispanic and Haitian migrant farmworkers. A random sample of labor camps in
      eastern North Carolina was selected. Blood samples were tested by Indirect
      Fluorescent Antibody techniques for plasmodial antibody and by enzyme-linked
      immunosorbent assay (ELISA) for cysticerci and T. cruzi antibodies.
      Questionnaires collected demographic data and medical history of the workers and
      family. Blood films stained with Leukostat stain were examined for plasmodia
      species. The seroprevalence of cysticercosis was 10 percent, T. cruzi 2 percent,
      and plasmodia species 4.4 percent. One case of active malaria (Plasmodium vivax)
      was demonstrated. The clinical significance of seropositivity was not determined,
      but these results suggest that a small but significant number of farmworkers are
      infected with cysticercosis, T. cruzi, and malaria. Migrant health clinicians
      should be aware of the possible presence of these infections. Greater observance
      and enforcement of sanitation regulations in farmwork is needed to prevent
      transmission of cysticercosis.

PMID- 8265759
TI  - Condom use among Hispanic men with secondary female sexual partners.
AB  - Greater understanding of psychosocial predictors of the use of condoms among
      Hispanics is needed in prevention efforts related to the human immunodeficiency
      virus and sexually transmitted disease epidemics among Hispanics in the United
      States. A telephone survey was carried out in nine States that have large
      populations of Hispanics, using a stratified clustered random digit dialing
      sampling strategy. The survey yielded interviews with 968 Hispanic men ages 18-49
      years. Of them, 361 (37.8 percent) reported at least one secondary female sexual
      partner in the 12 months prior to the interview. Predictors were identified of
      condom use by those men with their secondary sex partners. Key predictors of the
      subjects' condom use with secondary partners included carrying condoms; self
      efficacy, or a measure of the subject's perceived ability to use condoms under
      difficult circumstances; positive attitude toward condom use; having friends who
      used condoms; and lack of symptoms of depression in the week before the interview
      (R2 = 0.35). Significant predictors of condom carrying were being comfortable in
      sexual situations, positive attitude toward condom use, and self-efficacy to use
      condoms. Less acculturated men had more positive attitudes toward condom use and
      carried them more than did more acculturated men. The researchers found
      encouraging levels of condom use with secondary sexual partners among Hispanic
      men with multiple partners. Because of the large proportion of Hispanic men who
      have multiple partners and the severity of the sexually transmitted disease
      epidemics in the Hispanic community,health care providers should recommend to
      Hispanic men that they carry and use condoms,point out the acceptability of men
      using condoms,and assess and teach basic sexual information in that group.
      Referral may be appropriate for high risk Hispanic men with symptoms of
      depression.

PMID- 8265760
TI  - Patients' desires and satisfaction in general medicine clinics.
AB  - Most patients have explicit desires or requests when they visit their physicians.
      Identification of patients' requests and needs is the starting point of a patient
      centered approach to care. The frequency with which physicians met their
      patients' desires for services and that frequency's association with patient
      satisfaction were examined for 243 patients with chronic disease in general
      medicine clinics of a Department of Veterans Affairs hospital. Patients desired a
      mean of 11.9 services, of which an average of 67 percent were met. However, many
      patients' desires for information and most of their desires for help with
      emotional and family problems were not met. Patients with the most unmet desires
      for services, especially services related to information, were significantly less
      satisfied with their physicians than were those with fewer unmet desires. Factor
      analysis was used to develop a short, 16-item Requests for Services Questionnaire
      that appeared to cover the range of services that patients with chronic
      conditions desire. Enhancing physicians' ability to recognize and respond to
      patients' desires for services by using short patient request questionnaires may
      have the potential to improve patient satisfaction and other health care
      outcomes.

PMID- 8265761
TI  - Income and racial patterns of dietary vitamin C intake among black and white
      girls.
AB  - The authors examined the influence of income and race on mean dietary vitamin C
      intake and the risk of dietary vitamin C intake at levels below the recommended
      dietary allowance (RDA). They performed a cross-sectional analysis of 2,032 black
      and white 9- and 10-year-old females, from a wide range of income groups, who
      participated in the National Heart, Lung, and Blood Institute Growth and Health
      Study. Mean intake of vitamin C, exclusive of vitamin supplements and determined
      by 3-day diet records, exceeded the RDA of 45 milligrams per day for that age
      group in all racial and income categories. The investigators found that annual
      household income was directly associated with mean dietary vitamin C intake (P <
      0.0001) and that blacks had higher mean dietary vitamin C intakes than whites (P
      < 0.01). Among both blacks and whites, household income and risk of below-RDA
      vitamin C intake were inversely correlated, but this trend was statistically
      significant for blacks only (P < 0.05). Except for the lowest level income group
      (less than $10,000 per year), black girls from households with incomes less than
      $30,000 per year were at increased risk for below-RDA vitamin C intake (relative
      risk = 1.93 in the $10,000-$19,999 per year group and 1.63 in the $20,000-29,999
      per year group, P < 0.05), compared with black girls in the highest income
      category. One-quarter of white girls overall and more than 30 percent of white
      girls in the lowest two income groups had below-RDA vitamin C intakes. If the
      findings are generalizable,they underscore the importance of public health
      programs to address the adequacy of dietary vitamin C intake among preadolescent
      black and white females.

PMID- 8265762
TI  - Investigation of a staphylococcal food poisoning outbreak in a centralized school
      lunch program.
AB  - The trend in many communities toward centralized school lunch preparation
      potentially increases the risk of foodborne illness. Foods often are prepared
      long before serving and may be distributed to satellite schools by persons with
      little formal training in safe techniques of food preparation or food service. In
      May 1990, an outbreak of staphylococcal food poisoning occurred in elementary
      schools in a Rhode Island community participating in such a program. In the
      investigation of the outbreak, students in schools that reported cases were
      interviewed. Food preparation, handling, and distribution were reviewed. At
      School E, 662 lunches were prepared and distributed to 4 additional schools
      (schools A-D). Schools A and B accounted for nearly all cases of the food
      poisoning, with rates of 47 percent and 18 percent. Eating ham increased the risk
      of illness (62 percent of those consuming ham and 3 percent of those who did not,
      relative risk = 18.0, 95 percent confidence interval = 4.0, 313.4). Large amounts
      of Staphylococcus aureus were cultured, and preformed enterotoxin A was
      identified in leftover ham. A food handler, who tested positive for the
      implicated enterotoxic strain S. aureus, reported having removed the casings from
      two of nine warm ham rolls 48 hours prior to service. Because of improper
      refrigeration, prolonged handling, and inadequate reheating, the ham was held at
      temperatures estimated at 10-49 degrees Celsius (50-120 degrees Fahrenheit) for a
      minimum of 15 hours. The potential for larger outbreaks prompted a statewide
      training program in safe food preparation for school lunch personnel, which may
      have applications for other communities.

PMID- 8265763
TI  - Patterns and predictors of smoking cessation among users of a telephone hotline.
AB  - Most former cigarette smokers in the United States have stopped without formal
      assistance. However, a large proportion of smokers desire and seek help other
      than by attending formal programs. It is important to recognize what factors are
      likely to influence the effectiveness of smoking cessation attempts among these
      persons. The authors report results of a prospective cohort study of 1,552
      smokers who called a stop smoking hotline to request self-help smoking cessation
      information. The participants were classified into three groups based on reports
      at the 6-month followup: 242 quitters, 497 recidivists, and 813 nonquitters.
      Baseline and followup data were used to evaluate three comparisons: quitters
      versus nonquitters, quitters versus recidivists, and recidivists versus
      nonquitters. Nonquitters appear to be less motivated and more doubtful of their
      abilities to quit successfully compared with the other two groups. Quitters
      appear to live in a supportive environment for smoking cessation. Heavier smokers
      are more hesitant to try to quit, but once they make an attempt they are as
      likely to succeed as lighter smokers, when other factors are kept constant.
      Efforts to promote environments supportive of smoking cessation are likely to
      result in a larger number of successful quitters. Similarly, efforts to
      strengthen motivation and belief in personal ability to quit are likely to
      encourage more nonquitters to attempt to stop smoking. Finally, it appears that
      some smokers need a previous quit attempt before they are able to maintain
      cessation successfully.

PMID- 8265764
TI  - Saliva cotinine and recent smoking--evidence for a nonlinear relationship.
AB  - Cotinine concentration in various body fluids is considered to be among the most
      useful markers of nicotine exposure currently available. Despite the prevailing
      consensus concerning cotinine's usefulness, cotinine's large intrasubject
      variability has led some to question the value of a single-point measurement.
      Several individual differences (for example, age, race, sex, and so forth) may
      affect cotinine excretion, and a peculiar nonlinearity between the number of
      cigarettes smoked and cotinine concentration has been reported previously in the
      literature. The purpose of this investigation was to examine the nature of the
      association between cotinine and reported number of cigarettes smoked after
      adjustment for the relationship between cotinine and age, a key individual
      difference known to affect drug absorption, distribution, metabolism, excretion,
      and tissue sensitivity. The authors examined the relationship between saliva
      cotinine and daily cigarette consumption in 116 smokers (mean age = 37.4 years;
      average number of cigarettes smoked daily = 20.1) who logged each cigarette into
      a hand-held computer as part of a study on the accuracy of recall. The Pearson
      correlation between saliva cotinine and the logged number of cigarettes smoked in
      the previous 17 hours (the time window corresponding to the half-life of
      cotinine) accounted for significantly more of the variance in cotinine than did
      the average logged number of cigarettes smoked daily during 5 days. Age was also
      significantly associated with cotinine levels. Further examination of the
      relationship between cotinine and amount smoked in the previous 17 hours revealed
      evidence for a significant nonlinear component. Inclusion of both age and a cubic
      nonlinear component of daily cigarette consumption resulted in further
      significant improvement in the amount of variance accounted for in cotinine
      levels. These results suggest that adjustments forage and the inclusion of a
      nonlinear component for cigarette consumption will result in more precise use of
      cotinine as a validation tool for existing differences in smoking levels.

PMID- 8265765
TI  - Prevention strategies for infant walker-related injuries.
AB  - The estimated number of walker-related injuries to infants increased during the
      1980s, and standards for walker design safety remain voluntary with no monitoring
      to assess compliance. Although banning the walker has been proposed, this
      prevention strategy has not been employed. The most recent statistics available
      indicate that there were an estimated 27,804 walker-related injuries requiring
      emergency room attention among ages 0-4 years in 1991. Results of a survey of
      parents of 3-12-month-olds indicated considerable use of walkers, with greater
      use among parents with lower educational levels. Reported reasons for using
      walkers were for the infant's entertainment, enjoyment, and containment, as well
      as to help infants learn to walk. The authors recommend the consideration of a
      series of preventive strategies according to the epidemiologic framework for
      injury control and prevention designed by William Haddon, Jr. These include, but
      are not limited to, prohibiting the manufacture and sale of the walker, mandatory
      standards, redesign of the walker, design of an alternative to the walker, and
      consumer education to reduce use and to change patterns of use.

PMID- 8265766
TI  - New computer program presents public health data in map form.

PMID- 8265767
TI  - Modern management of asthma in adults.

PMID- 8265768
TI  - The use of herpes simplex virus vectors for gene therapy in neurological
      diseases.
AB  - Herpes simplex virus type 1 (HSV-1) vectors have now been developed and enable
      the efficient delivery of foreign genes under the control of appropriate promoter
      elements into non-dividing neurons in vitro and in vivo. Their use is based on
      the natural ability of HSV-1 to spread throughout the nervous system and to
      establish a lifelong latent infection in neurons. HSV is present in an episomal
      form in the neuronal nucleus, and normal neuronal functions remain unaltered. A
      wide variety of foreign genes can theoretically be packaged into the large HSV
      genome. A number of technical problems will need to be overcome to ensure the
      stable expression of the foreign gene products, adequate control of the levels of
      their expression, the safety of the vectors and the correct targeting of the
      vectors to the appropriate neuronal cell populations. Such vectors have the
      potential to replace missing gene products in neurons in patients with a variety
      of metabolic and neurodegenerative diseases, and also to insert growth factors or
      enzymes into the local vicinity of neurological lesions to promote neuronal
      repair. HSV-1 vectors also have the potential to define the genetic basis of
      various neurophysiological functions which may prove to be useful in evaluating
      altered neuronal function encountered in disease.

PMID- 8265769
TI  - Maternal plasma folate and vitamin B12 are independent risk factors for neural
      tube defects.
AB  - Blood was taken at the first antenatal clinic from 56,049 pregnant women. Neural
      tube defect (NTD) pregnancies (81) were compared to controls (247) for plasma
      vitamin B12 (B12) (ng/l), plasma folate (microgram/l), and red cell folate (RCF)
      (microgram/l). Median values were significantly different and were, respectively,
      243 and 296 (p = 0.001); 3.47 and 4.59 (p = 0.002); and 269 and 338 (p < 0.001).
      There was a significant correlation between plasma B12 and RCF in cases (r =
      0.31, p = 0.004) but not in controls (r = 0.02, p = 0.725). In cases only,
      multiple regression showed that both plasma B12 and plasma folate influenced the
      maternal RCF (multiple r = 0.68, p < 0.001). Plasma folate and plasma B12 were
      independent risk factors for NTDs, suggesting that the enzyme methionine synthase
      is involved directly or indirectly in the aetiology. The levels of folate and B12
      where increased risk occurred were not those usually associated with deficiency,
      calling for a re-evaluation of their recommended daily allowances. Whether the
      aetiology is purely nutritional or a metabolic defect, this study suggests that
      consideration should be given to including B12 as well as folic acid in any
      programme of supplementation or food fortification to prevent NTDs.

PMID- 8265770
TI  - Mitochondrial myopathy associated with sudden death in young adults and a novel
      mutation in the mitochondrial DNA leucine transfer RNA(UUR) gene.
AB  - A family exhibited maternal inheritance of a variable syndrome comprising ocular,
      neck and proximal upper limb weakness, psychiatric features, and sudden death. Of
      15 definitely or probably affected individuals, 7 had died in early adult life,
      probably of respiratory failure. A novel point mutation of mitochondrial DNA, in
      a transfer RNA gene at position 3251, was detected in all living affected family
      members.

PMID- 8265771
TI  - The role of skin biopsies in bone marrow transplant recipients.
AB  - Bone marrow transplant (BMT) recipients frequently develop rashes as a
      consequence of their disease, its treatment or because of a complication such as
      infection. These rashes are often clinically atypical, yet appropriate management
      is dependent upon correct diagnosis and therefore a skin biopsy is often
      performed. In a group of 101 consecutive BMT recipients, 25 patients had a total
      of 34 skin biopsies. A specific histopathological diagnosis was made in 65%
      (22/34), including graft vs. host disease (GVHD) (15 cases), infection (4 cases),
      drug reaction (1 case) and recurrent lymphoma (1 case). Therapy was changed
      following the biopsy in 77% (17/22) of these cases. In 35% (12/34) the
      histological changes were non-specific, however, in 10 of these cases GVHD had
      been suspected clinically and its exclusion was therefore useful. Skin biopsy is
      of considerable value in the diagnosis and subsequent management of BMT
      recipients who develop a rash.

PMID- 8265772
TI  - Ocular manifestations of classical and limited Wegener's granulomatosis.
AB  - Wegener's granulomatosis (WG) may be subdivided into two forms, classical and
      limited. The latter specifically excludes renal disease and carries a better
      prognosis. Both forms have sight-threatening complications, but the relative
      incidence of ocular manifestations in each is not well documented. Patients with
      limited (n = 15) and classical (n = 16) WG were ophthalmologically examined.
      Ocular abnormalities found included orbital and nasolacrimal disease, corneo
      scleral inflammation, dry eyes and retinal vein occlusion. In four patients (two
      from each group), no ocular disease was detected. The limited group included four
      potentially sight-threatening complications, compared to eight in the classical
      group. Overall, there was no statistically significant difference in any of the
      ocular manifestations between the two groups. Although treatment with
      corticosteroid and immunosuppressive agents has dramatically improved the
      prognosis of the disease, ocular morbidity is still well recognized. A combined
      medical and ophthalmological approach with prompt therapeutic intervention is
      recommended in these patients.

PMID- 8265773
TI  - Antiendothelial cell antibodies in lupus: correlations with renal injury and
      circulating markers of endothelial damage.
AB  - Systemic lupus erythematosus is characterized by the production of a broad
      spectrum of autoantibodies. Autoantibodies directed against endothelial cells
      (AECA) have been particularly well documented. We investigated associations
      between such antibodies, double-stranded DNA (dsDNAb), phospholipid (cardiolipin,
      ACA), and indices of activity and chronicity scored on renal biopsy specimens
      from 22 patients with acute lupus. AECA were present in 73% of these patients,
      and both the percentage of patients with AECA and the mean antibody titre fell
      significantly as patients entered remission. When patients already on
      immunosuppressive therapy were excluded from analysis (n = 7), only levels of
      AECA and DNAb (p = 0.02) correlated with histological evidence of active lesions
      and the presence of glomerular epithelial cell crescents; no correlation was
      found with chronic changes in the renal biopsies. Serum von Willebrand factor
      (vWf) and serum total protein S levels, two parameters reflecting endothelial
      cell function, were also measured during acute disease and remission. vWf
      concentrations were elevated during acute disease (m = 1.9 IU/ml, p = 0.02), but
      the values did not correlate with AECA titres. In contrast, total protein S
      levels were reduced (0.81 IU/ml vs. 0.97 IU/ml, p = 0.01) during active disease,
      but remained within the normal range (0.56-1.16 IU/ml). Furthermore, protein S
      levels were inversely related to levels of AECA (r = -0.4, p = 0.01). AECA were
      therefore present in most patients with acute lupus nephritis and were associated
      with histological evidence of active renal injury and serological evidence of
      endothelial cell dysfunction. These data provide indirect support for a
      pathogenic role for AECA in lupus nephritis.

PMID- 8265774
TI  - Serious complications associated with Dettol poisoning.
AB  - Dettol is involved in 10% of self-poisoning-related hospital admissions in Hong
      Kong. Although serious poisonings and even deaths after ingesting this common
      household disinfectant have been reported, the frequency with which these
      complications may occur is not known. In a retrospective study of 67 cases of
      Dettol poisoning, we found that serious complications were relatively common (8%)
      and these included aspiration of Dettol with gastric contents resulting in
      pneumonia, cardiopulmonary arrest, bronchospasm, adult respiratory distress
      syndrome, and severe laryngeal oedema with upper airways obstruction. It is
      particularly important that the airways are adequately protected before the
      patient is lavaged following Dettol poisoning, and the immediate recognition of
      any upper airway obstruction requiring intubation will then be life-saving.

PMID- 8265775
TI  - Mean platelet volume in diabetes mellitus.
AB  - We measured mean platelet volume (MPV) in patients with diabetes mellitus,
      compared with MPV in non-diabetic control subjects. Mean MPV was significantly
      increased in the diabetic subjects (8.9 +/- 0.07 fL, mean +/- SEM) compared with
      non-diabetic subjects (8.0 +/- 0.05) (p < 0.001). Since platelet size is a
      determinant of platelet function, with larger platelets being more reactive per
      unit volume, we believe platelets may play a part in the micro- and macro
      vascular complications of diabetes mellitus.

PMID- 8265776
TI  - Helicobacter pylori eradication: efficacy and side effect profile of a
      combination of omeprazole, amoxycillin and metronidazole compared with four
      alternative regimens.
AB  - We evaluated eradication of Helicobacter pylori infection in 263 patients by a
      new 14-day regimen of omeprazole 40 mg mane (a gastric secretory inhibitor) plus
      two antibiotics: amoxycillin 500 mg three-times daily (tds) plus metronidazole
      400 mg tds. The comparative groups included updated results of our previous work
      with a 14-day course of either standard triple therapy (STT, colloidal bismuth
      subcitrate 120 mg four times daily (qds) plus tetracycline 500 mg qds and
      metronidazole 400 mg tds), omeprazole 40 mg once daily plus amoxycillin 500 mg
      tds (OA), or two modified triple therapy: either Borody's (BTT) of all three
      components (colloidal bismuth subcitrate 120 mg, tetracycline 500 mg,
      metronidazole 200 mg) qds instead of tds, or Logan's (LTT) seven-day therapeutic
      regimen of colloidal bismuth subcitrate 120 mg qds, amoxycillin 500 mg qds and,
      for the last three days, metronidazole 400 mg five times daily.
      Omeprazole/amoxycillin/metronidazole (OAM) therapy was better tolerated than STT
      (course completion 98.1% vs. 81.4%, p < 0.001). H. pylori was eradicated by OAM
      therapy in 53/55 (96.4%) patients with metronidazole-sensitive organisms and in
      54/72 (75.0%) with metronidazole-resistant isolates (p < 0.01). The respective
      corresponding rates for STT and OA therapy were 20/22 (90.9%) and 14/29 (48.3%),
      (metronidazole-sensitive organisms) and 7/21 (33.3%) and 15/31 (48.4%)
      (infections resistant to metronidazole). BTT and LTT were also better tolerated
      than STT. The eradication rate for BTT was 23/26 (88.5%) but that for LTT, the
      best tolerated of the five treatment regimens, was only 19/28 (67.9%) when
      pretreatment isolates were metronidazole-sensitive.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8265777
TI  - The effects of ionizing radiation on avian erythrocytes.
AB  - The effects of ionizing radiation were examined in terminally differentiated
      cells using nucleated chicken erythrocytes (RBCs) as the model. We used a
      hemolytic assay to score radiation damage to RBCs. Chicken RBCs received 0 to 100
      Gy of radiation at dose rate of 10 Gy/min. Radiation-induced hemolysis occurred
      in a dose-dependent manner but not immediately after irradiation. Hemolysis
      became apparent at 24 h after treatment. A threshold for radiation dose response
      was observed. At doses below 30 Gy, hemolysis in irradiated samples was
      indistinguishable from that in nonirradiated controls. A total dose of 100 Gy was
      used for the split-dose experiments. The results showed that chicken RBCs were
      able to repair radiation damage and that the half-time for maximum recovery was
      approximately 30 min at 36 degrees C. Recovery from gamma radiation was also
      affected by the interfraction temperature.

PMID- 8265778
TI  - Dose conversion factors and linear energy transfer for irradiation of thin blood
      layers with low-energy X rays.
AB  - For irradiation of thin samples of biological material with low-energy X rays,
      conversion of measured air kerma, free in air to average absorbed dose to the
      sample is necessary. In the present paper, conversion factors from measured air
      kerma to average absorbed dose in thin blood samples are given for four low
      energy X-ray qualities (14-50 kVp). These factors were obtained by Monte Carlo
      simulation of a practical sample holder. Data for different thicknesses of the
      blood and backing layer are presented. The conversion factors are found to depend
      strongly on the thicknesses of the blood layer and backing layer. In
      radiobiological work, knowledge of linear energy transfer (LET) values for the
      radiation quality used is often required. Track-averaged LET values for low
      energy X rays are presented in this work. It is concluded that the thickness of
      the sample does not influence the LET value appreciably, indicating that for all
      radiobiological purposes this value can be regarded as a constant throughout the
      sample. Furthermore, the large difference between the LET value for a 50 kV
      spectrum found in this work and the value given in ICRU Report 16 is pointed out.

PMID- 8265779
TI  - Effect of 3H decays on DNA partition during cell division.
AB  - Normal human embryonic lung fibroblasts were grown in the presence of different
      concentrations of tritium-labeled thymidine ([3H]dThd) for various periods of
      time, and the flow of cells from metaphase to anaphase was followed. Mitotic
      indices were evaluated as a function of the percentage of cells in metaphase and
      anaphase. They revealed that the presence of [3H]dThd induces a disturbance of
      the metaphase-anaphase transition. The DNA content of cells in metaphase and
      anaphase was measured with cytophotometry after the cells were grown in the
      presence of the radioactive precursor. It was found that the latter interfered
      with the flow of cells from metaphase to anaphase, impairing the symmetric
      distribution of DNA between daughter cells.

PMID- 8265780
TI  - Plutonium-catalyzed oxidative DNA damage in the absence of significant alpha
      particle decay.
AB  - Plutonium is considered to be a carcinogen because it emits alpha particles that
      may result in the irradiation of stem cell population. In the present study we
      show that plutonium can also catalyze reactions that induce hydroxyl radicals in
      the absence of significant alpha-particle irradiation. Using the low specific
      activity isotope, 242Pu, experiments were performed under conditions in which
      chemical generation of hydroxyl radicals was expected to exceed the radiolytic
      generation by one hundred thousand-fold. The results showed that markers of
      oxidative DNA base damage, thymine glycol and 8-oxoguanine could be induced from
      plutonium-catalyzed reactions of hydrogen peroxide and ascorbate similarly to
      those occurring in the presence of iron catalysts. Plutonium-242, as a
      neutralized nitrate in phosphate buffer, was 4.8-fold more efficient than iron at
      catalyzing the oxidation of ascorbate at pH 7. The results suggest that plutonium
      complexes could participate in reactions at pH 7 that induce oxidative stress--a
      significant tumor-promoting factor in generally accepted models of
      carcinogenesis.

PMID- 8265781
TI  - Age and radiation sensitivity of rat mammary clonogenic cells.
AB  - The relative risk of breast cancer is very high among women who were exposed to
      ionizing radiation during or before puberty. In the current studies, the
      surviving fractions of clonogenic mammary cells of groups of virgin rats were
      estimated after single exposures to 137Cs gamma rays at intervals from 1 to 12
      weeks after birth. The radiosensitivity of clonogens from prepubertal rats was
      high and changed with the onset of puberty at between 4 and 6 weeks of age. By
      this time, the increase in the size of the clonogenic cell subpopulation was
      slowing and differentiation of terminal mammary end buds and alveolar structures
      was occurring. Analysis of the relationship of clonogen survival and radiation
      dose according to the alpha/beta model showed that the exponential alpha D term
      predominated at the second and fourth weeks of age. By the eighth week of age,
      the beta D2 term had come to predominate and the survival curve had a pronounced
      initial convex shoulder. Further experiments are required to determine whether
      there is an association between the high sensitivity of the prepubertal and
      pubertal mammary clonogens to radiation killing and a high susceptibility to
      radiogenic initiation of cancer.

PMID- 8265782
TI  - Corrections to the paper "Fitting the Armitage-Doll model to radiation-exposed
      cohorts and implications for population cancer risks.

PMID- 8265783
TI  - A comparison of calculated and measured W values in tissue-equivalent gas
      mixtures.
AB  - We calculated the mean energy required to produce an ion pair (W) in methane-,
      propane- and butane-based tissue-equivalent (TE) gas mixtures from W values in
      pure constituent gases according to various models for energy partition among gas
      components. We found an agreement between the experimental and calculated W
      values in the methane-based TE gas regardless of the model concept. In contrast,
      only those models which take into account differences in the stopping powers,
      total ionization cross sections and model constants of gas components give
      acceptable results for the propane-based TE gas. The calculated W value for high
      energy electrons in the isobutane-based TE gas mixture is 25.2 eV for high-energy
      electrons and 28.0 eV for approximately 5 MeV alpha particles.

PMID- 8265784
TI  - The influence of hydration on the absolute yields of primary free radicals in
      gamma-irradiated DNA at 77 K. II. Individual radical yields.
AB  - In this report we present an electron spin resonance (ESR) investigation of the
      yields of the individual free radicals formed in gamma-irradiated frozen DNA as a
      function of hydration and dose at 77 K. Analysis of the ESR spectra taken at low
      hydration shows that the ion radical composition remains nearly constant with
      dose and that few secondary radicals are formed even at high doses (above about
      50 kGy). For fully hydrated samples, the radical composition changes dramatically
      with dose. Thymine anion radical (T-.) is found in abundance at low doses but
      nearly disappears at higher doses, with a corresponding increase in the N-3
      deuterated cytosine anion radical (CD.). Guanine cation radical (G+.) decreases
      at high doses, with a concomitant increase in secondary radical species (S.).
      Analysis of the dose-response data for G values (the yields in microM/J), k
      values (the destruction constants) and k' values (a new constant that
      characterizes the change in G with dose) was performed for each of the DNA base
      free radicals present at 77 K. The G value for each of the base radicals
      increases with the hydration level. The k values for CD. and G+. increase
      slightly with hydration; however, that of T-. increases substantially.
      Destruction constants for neutral radicals such as TH. and CD. are found to be
      substantially smaller than those for ion radicals and provide an indication of
      the radical charge state. A negative k' value for T-. and a positive k' value for
      CD. are explained in terms of radiation effects that result in the formation of a
      deuterated cytosine base, i.e., C(N3)D+, which greatly increases cytosine's
      electron affinity. The ratio of anion radical to cation radical concentrations is
      found to be about 1.6 and is invariant with hydration. A speculation on the
      imbalance based on hole-hole combinations in spurs is presented.

PMID- 8265785
TI  - Radiosensitivity of CD45RO+ memory and CD45RO- naive T cells in culture.
AB  - Radiosensitivities of various human T-cell subsets were investigated by a
      proliferation assay and by a single-cell gel electrophoresis assay. Each T-cell
      subset was purified using a cell sorter and was induced to proliferate by
      ionomycin and interleukin 2. Unsorted T cells showed biphasic dose-survival
      curves, indicating the heterogeneity of T cells in terms of radiosensitivity.
      Purified CD4+ helper and CD8+ killer T cells showed similar biphasic dose
      survival curves. Hence both T-cell subsets were composed of cells of different
      radiosensitivity. The T-cell subsets belonging to different activation stages
      such as CD45RO+ memory and CD45RO- naive T cells had different dose-survival
      curves. The former was more radiosensitive than the latter. The high
      radiosensitivity of CD45RO+ cells was also demonstrated by single-cell gel
      electrophoresis after irradiation. This is the first demonstration that a
      particular cell surface marker on T cells is correlated with greater
      radiosensitivity.

PMID- 8265786
TI  - Radiation-induced damage, repair and exchange formation in different chromosomes
      of human fibroblasts determined by fluorescence in situ hybridization.
AB  - We have used fluorescence in situ hybridization with whole-chromosome probes for
      human chromosomes 1, 4, 8 and 13 to investigate the extent to which the induction
      of damage and its repair after exposure to ionizing radiation is distributed
      randomly among these chromosomes. All the studies were performed with AG1522
      human fibroblasts irradiated with 6 Gy and maintained in a nondividing state for
      at least 6 h after irradiation except for the measurements of initial damage. The
      extent of initial damage was determined by fusion of the cells immediately after
      irradiation with metaphase HeLa cells to obtain premature chromosome condensation
      (PCC). Breaks and exchanges were also scored by PCC 24 h after irradiation and in
      metaphase spreads at the first division after irradiation. The data obtained were
      consistent with random breakage and repair in these chromosomes. Comparing PCC 24
      h after irradiation with first metaphase, there was a deficit in aberrations at
      metaphase, particularly in unrejoined breaks, implying loss or slowing of cells
      containing aberrations prior to the first division. An analysis of dicentrics and
      translocations in chromosome 4 at first and in subsequent divisions showed that
      there was an equal number of dicentrics and translocations at first metaphase
      with loss of dicentrics, but no loss of translocations in subsequent divisions.
      These data are supportive of the hypothesis tht the total number of chromosome
      aberrations in cells can be estimated from a single chromosome pair.

PMID- 8265787
TI  - Neutron capture therapy of a rat glioma using boronophenylalanine as a capture
      agent.
AB  - The purpose of the present study was to determine the efficacy of boron neutron
      capture therapy (BNCT) in treating the therapeutically refractory F98 glioma,
      using boronophenylalanine (BPA) as the capture agent. F98 glioma cells (10(5))
      were implanted stereotactically into the brains of Fischer rats and 15 days later
      the animals were injected intraperitoneally with 897 mg/kg of D,L-BPA. Between 3
      and 9 h after administration blood and tumor boron concentrations exhibited
      monoexponential decay with half-lives (t1/2) of 4.3 and 5.3 h, respectively. When
      803 mg/kg of 10B-L-BPA was administered, the tumor 10B concentration was 29.4
      micrograms/g and tumor-to-blood and tumor-to-brain ratios were 3.5 and 3.9,
      respectively. Seven days after intracerebral implantation of 10(5) F98 cells,
      BNCT was initiated at the Brookhaven Medical Research Reactor. The median
      survival time for irradiated controls (no BPA), which had received tumor physical
      doses of 1.7, 2.6 or 3.5 Gy, were 27, 33 and 38 days, respectively, compared to
      24 days for untreated rats (P < or = 0.025-0.0001). The median survival time for
      BNCT-treated groups that had received 803 mg/kg of 10B-L-BPA 6 h prior to
      irradiation with total estimated tumor physical doses of 5.7, 8.6 and 11.5 Gy
      were 32, 37 and 59 days, respectively. Although the enhanced median survival
      times of two of the BNCT-treated group (8.6 and 11.5 Gy) were significant
      compared to their matched irradiated controls (P < or = 0.0175-0.0277), all BNCT
      treated animals died in less than 160 days. It remains to be determined whether
      better survival can be achieved using higher doses of BPA and neutrons to treat a
      tumor, which at this time cannot be cured by any therapeutic modality.

PMID- 8265788
TI  - Athermal alterations in the structure of the canalicular membrane and ATPase
      activity induced by thermal levels of microwave radiation.
AB  - Sprague-Dawley rats (200-250 g) were exposed 30 min/day for 4 days to thermogenic
      levels (rectal temperature increase of 2.2 degrees C) of microwave radiation
      [2.45 GHz, 80 mW/cm2, continuous-wave mode (CW)] or to a radiant heat source
      resulting in an equivalent increase in body temperature of 2.2 degrees C. On the
      fifth day after the 4 days of exposure to microwave radiation, the animals were
      sacrificed and their livers removed. The canalicular membranes were isolated and
      evaluated for adenosinetriphosphatase (ATPase) activity, total fatty acid
      composition and membrane fluidity characteristics. Mg(++)-ATPase activity (Vmax)
      decreased by 48.5% in the group exposed to microwave radiation, with no
      significant change in the group exposed to radiant heat. The decrease in Mg(++)
      ATPase was partially compensated by a concomitant increase in Na+/K(+)-ATPase
      activity (170% increase in Vmax over control) in animals exposed to microwave
      radiation, while no change occurred in the group exposed to radiant heat. This
      alteration in ATPase activity in the group exposed to microwave radiation is
      associated with a large decrease in the ratio of saturated to unsaturated fatty
      acids. Conversely, the group exposed to radiant heat had an increase in the ratio
      of saturated to unsaturated fatty acids. The most dramatic changes were found in
      the levels of arachidonic acid. Finally, the electron paramagnetic resonance
      (EPR) spin label technique used to measure the fluidity of the canalicular
      membranes of the animals in the three groups (sham, microwave radiation and
      radiant heat) indicated that the results were different in the three groups,
      reflecting the changes found in their fatty acid composition. The physiological
      response to "equivalent" thermal loads in rats is expressed differently for
      different types of energy sources. Possible mechanisms producing these divergent
      thermogenic responses are discussed.

PMID- 8265789
TI  - Effects of acute irradiation on reproductive success of the polychaete worm,
      Neanthes arenaceodentata.
AB  - Effects of acute irradiation on the reproductive success of a relatively low
      fecundity species were investigated by exposing pairs of female and male
      polychaete worms (Neanthes arenaceodentata) to either no radiation (controls) or
      0.5, 1.0, 2.0, 5.0, 10 or 50 Gy of acute irradiation (5 Gy min-1) at the time
      when oocytes were visible in the female. The broods from the pairs were
      sacrificed before hatching occurred, and information was obtained on the number
      in the brood, the number of normal and abnormal embryos, and the number of
      embryos that were living, dying and dead. Developing gametes of N.
      arenaceodentata appeared to be sensitive to acute irradiation. There was a
      significant reduction in the percentage of live embryos in the broods from pairs
      receiving doses as low as 0.5 Gy, which is lower than the lowest dose at which
      effects in invertebrates have been reported previously. This was most likely due
      to the induction of lethal mutations in the developing gametes, which affected
      the survival of embryos in early stages of life. Except for those pairs receiving
      10 or 50 Gy, there was no evidence of decreased fertility or fecundity or of
      reduced fertilization success; the number of embryos in the broods from only
      these irradiated groups was significantly different from the controls.

PMID- 8265790
TI  - Radiosensitivity of polyamine-depleted HeLa cells and modulation by the
      aminothiol WR-1065.
AB  - The radiosensitivity of cultured HeLa cells was increased upon depletion of the
      natural cellular polyamines putrescine, spermidine and spermine through treatment
      of cultures with inhibitors of polyamine biosynthesis. This increased
      radiosensitivity was manifested as a decrease in the D0 and by the absence of a
      shoulder in the survival curves. However, our previous studies have shown that
      the initial yield of X-ray-induced DNA damage did not appear to be elevated in
      polyamine-depleted cells. In addition, polyamine-depleted cells exhibited
      markedly altered X-ray-induced changes in the distribution of cells in the phases
      of the cell cycle characterized by increased time of onset and lengthened
      duration of G2-phase delay. Addition of polyamines to cultures for short periods
      prior to irradiation restored normal radioresistance and reversed the anomalous
      features of the G2-phase delay profile. Polyamine supplementation experiments as
      well as studies in which combinations of inhibitors were employed to modulate
      specific polyamine levels suggest that spermidine may play a primary role in
      governing cellular radioresponsiveness. The radioprotective aminothiol WR-1065
      protected normal and polyamine-depleted cells to a proportionately similar extent
      (protection factor of 2.4 and 2.8, respectively) but had no apparent ability to
      restore the shoulder or alter the G2-phase delay markedly in polyamine-depleted
      cells. The findings reported here extend our previous observations that polyamine
      depletion results in a compromised ability to respond to X irradiation and
      suggest that a defect in repair and/or the G2-phase delay response may be the
      determining factors.

PMID- 8265791
TI  - Inhibiting the repair of DNA damage induced by gamma irradiation in rat
      thymocytes.
AB  - This study assessed the ability of 11 established and potential radiosensitizing
      agents to retard the repair of radiation-induced DNA damage with a view to
      enhancing the immunosuppressive effects of in vivo lymphoid irradiation. The
      capability of irradiated rat thymocytes to repair DNA damage was assessed by an
      adaptation of the fluorimetric unwinding method. Three compounds, 3
      aminobenzamide (3-AB), novobiocin and flavone-8-acetic acid (FAA), inhibited
      repair significantly. We also report the effect of low-dose irradiation combined
      with repair inhibitors on the relationship between DNA strand breaks,
      fragmentation, cell viability and use of nicotinamide adenine dinucleotide (NAD).
      DNA fragmentation was increased by 1 mM/1 FAA, 1 mM/l novobiocin and 50 microM/l
      RS-61443 within 3 h of incubation. The latter two compounds also proved
      cytotoxic. All three drugs augmented the effect of ionizing radiation on the use
      of NAD. Of the agents investigated, FAA showed the most promise for augmenting
      the immunosuppressive action of irradiation at nontoxic, pharmacokinetically
      achievable concentrations.

PMID- 8265792
TI  - Autoantibodies and immunoglobulins among atomic bomb survivors.
AB  - The purpose of this study was to determine if exposure to atomic bomb radiation
      affects immune responsiveness, such as the occurrence of autoantibodies and
      levels of immunoglobulins. Rheumatoid factor, antinuclear antibody,
      antithyroglobulin antibody, anti-thyroid-microsomal antibody and immunoglobulin
      levels (IgG, IgM, IgA and IgE) were measured among 2,061 individuals exposed to
      atomic bomb radiation in Hiroshima and Nagasaki whose estimated doses ranged from
      0 to 5.6 Gy. The prevalence and titers of rheumatoid factor were found to be
      increased in the individuals exposed to higher radiation doses. The IgA level in
      females and the IgM level in both sexes increased as radiation dose increased,
      although the effects of radiation exposure were not large. No effect of radiation
      was found on the prevalence of antinuclear antibody, antithyroglobulin antibody
      and anti-thyroid-microsomal antibody or on the levels of IgG and IgE.

PMID- 8265793
TI  - Levels of parathyroid hormone and calcitonin in serum among atomic bomb
      survivors.
AB  - To examine the potential causes of increased levels of calcium in serum with
      increasing dose of atomic bomb radiation, which was obtained from the previous
      preliminary analysis, levels of parathyroid hormone (PTH) and calcitonin in serum
      were examined among 1459 subjects in Hiroshima and Nagasaki. A significant effect
      of radiation on levels of calcium, PTH and calcitonin in serum was found, even
      after patients with hyperparathyroidism were excluded. The level of calcium in
      serum increased with radiation dose; this can be explained partly by the increase
      in the level of PTH with radiation dose. However, the dose effect on calcium
      remained even after adjustment for PTH, calcitonin and confounding factors such
      as renal function, serum albumin level and medication. Parathyroid hormone
      increased initially by 6.8% per gray, but the dose response leveled off after
      about 1 Gy. The level of calcitonin increased with radiation dose, probably in
      part due to feedback mechanisms stimulated by the increase in calcium. However,
      after adjustment for the level of calcium, the increase in the level of
      calcitonin with dose was still found. Although the etiological mechanisms of the
      effect of radiation on serum levels of calcium, PTH and calcitonin are unclear,
      radiation exposure may affect secretion of PTH and calcitonin and regulation of
      calcium a long time after atomic bomb exposure.

PMID- 8265794
TI  - Nurse sues hospital for sexual harassment.

PMID- 8265795
TI  - Refusal to return meds: pt. threatens & commits suicide. Case in point: Hartley
      v. Kassen 859 S.W. 2d 367--TX (1992).

PMID- 8265796
TI  - Legal case briefs for nurses. IA: unattended pt. falls in bathroom: "routine
      nonmedicale care" standard applied; OR: nurses state "all sponges ... removed":
      court rejects "captain of ship" doctrine.

PMID- 8265797
TI  - Care allegedly provided without proper supervision. Case in point: Raicevich v.
      Plum Creek Medical P.C. 918 F. Supp. 2d 929--CO (1993).

PMID- 8265798
TI  - The plasma membrane of uterine epithelial cells: structure and histochemistry.

PMID- 8265799
TI  - Expression and regulation of the tumour necrosis factor-alpha gene in the female
      reproductive tract.
AB  - Tumour necrosis factor-alpha (TNF), a potent cytokine originally identified as a
      product of activated macrophages, is now known to be produced by many types of
      cells, and has been implicated in regulation of normal tissue homeostasis as well
      as in cellular differentiation. In humans and some murids, the TNF gene is
      expressed in ovaries, oviducts, uteri, placentas and embryos. Specific
      transcripts and proteins have been identified in oocytes, granulosa and theca
      cells, luminal and glandular epithelial cells, myometrial cells, decidual cells,
      placental trophoblast, macrophage-like cells and embryonic skin. Both prior and
      subsequent to implantation, uterine TNF mRNA and protein appear in specific cell
      lineages in an ordered temporal sequence. This and other findings indicate that
      transcription of the TNF gene in the uterus is regulated either directly or
      indirectly by ovarian and/or placental hormones. By contrast, there is as yet no
      evidence for regulation of this gene by other uterine cytokines such as colony
      stimulating factor-1 (CSF-1). Although the functions of this pleiotrophic,
      multifunctional molecule are largely unknown, the findings to date are consistent
      with the postulate that TNF is involved in gamete development, cyclic changes in
      the uterus, cancers of the female reproductive tract, placental maturation and
      embryonic development.

PMID- 8265800
TI  - Sex predetermination by separation of X and Y chromosome-bearing sperm: a review.

PMID- 8265801
TI  - Active immunization of Merino ewe lambs with recombinant bovine alpha inhibin
      advances puberty and increases ovulation rate.
AB  - Ewe lambs (n = 24-25) were immunized at 3, 7 and 15 weeks of age with recombinant
      bovine alpha-inhibin (rec inhibin) or with bovine monoclonal antibody purified
      inhibin (bMPI) obtained by immunochromatography from bovine follicular fluid or
      with adjuvant alone (control). Antibodies in the plasma of the lambs immunized
      with the inhibin preparations bound to iodinated 31 kDa bovine inhibin. Binding
      was minimal after the primary immunization, increased after each booster
      immunization and remained elevated until at least 45 weeks of age (29% for rec
      inhibin and 11% for bMPI). Of the group treated with rec inhibin, 10 ovulated as
      lambs (control 0/22; bMPI 3/21) and onset of overt oestrous activity (as hoggets)
      was advanced (P < 0.05) by 17 days in lambs immunized with rec inhibin. As
      hoggets, the ovulation rate was greater (P < 0.01) in the rec inhibin immunized
      lambs (4.41 +/- 0.67) than in the control animals (1.27 +/- 0.15) but not in the
      bMPI-treated lambs (1.40 +/- 0.16). After a further immunization at 17 months of
      age, however, ovulation rate increased (P < 0.01) in the bMPI-immunized group
      (3.40 +/- 0.47) but was unchanged in the lambs immunized with rec inhibin (2.80
      +/- 0.52) and those in the control group (1.15 +/- 0.08). There were no effects
      of immunization on plasma concentrations of either follicle stimulating hormone
      (FSH) or luteinizing hormone (LH). The initial smaller response seen with the
      bMPI may be due to either the presence of compounds other than inhibin in such
      preparations or the small absolute amount of inhibin injected.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8265802
TI  - Biopotency in vitro and metabolic clearance rates of five pituitary preparations
      of follicle stimulating hormone.
AB  - Five pituitary preparations of follicle stimulating hormone (FSH), namely NIDDK
      oFSH-17, Bioscan oFSH, Ovagen, Folltropin-V and F.S.H.-P., were examined for
      biological activity in terms of their potency in an in vitro bioassay, receptor
      assay and heterologous radioimmunoassay and in terms of their metabolic clearance
      rates. In the three assays, Bioscan oFSH was the most potent (P < 0.05) (3- to 5
      fold the potency of NIDDK-oFSH-17), with Ovagen being 25-50% the potency of the
      NIDDK standard (P < 0.05). Folltropin-V and F.S.H.-P. had the lowest potencies in
      all three assays. For each preparation, the ratio of activities between the
      assays was not consistent, suggesting that the preparations behaved differently
      in each assay. In 9 of 10 cases, potency estimates in the heterologous
      radioimmunoassay were greater than those in the in vitro bioassay or receptor
      assay. Polyacrylamide gel electrophoresis of the preparations showed banding
      consistent with the molecular weight of FSH, but also indicated that the
      preparations were contaminated with other proteins to varying extents. The half
      lives of these preparations when injected into the bloodstream of mature female
      mice were 28.0, 8.6, 13.4, 11.6 and 17.4 min for NIDDK-oFSH-17, Bioscan oFSH,
      Ovagen, Folltropin-V and F.S.H.-P. respectively. The slopes of the decay rates
      were significantly different from each other (P < 0.05) except between Ovagen and
      Folltropin-V. The results of these studies show that a number of widely available
      FSH preparations have differing biopotencies. Moreover, the biopotency of a
      preparation in vitro is not related to its metabolic clearance rate, and not all
      FSH preparations behave identically in different assays. Measures of biopotency
      in vitro combined with those of metabolic clearance rate may provide useful
      information on the properties of FSH preparations used for research purposes and
      for superovulation of farmed livestock.

PMID- 8265803
TI  - Conceptus development in vivo, endometrial and conceptus protein release in vitro
      following blastocyst transfer to ewes induced to ovulate at 28 days post-partum.
AB  - The use of laparoscopic insemination to deposit semen into the tip of the uterine
      horn ensures fertilization in ewes induced to ovulate at 3-5 weeks post-partum.
      Acceptable pregnancy rates are achieved if embryos from post-partum donors are
      transferred to a normal uterine environment yet embryos rarely survive when
      transferred or returned to a post-partum uterus. Blastocyst transfer procedures
      were developed to test whether the post-partum uterus can support conceptus
      development during the period of rapid growth coincident with the maternal
      recognition of pregnancy. In Experiment 1, the efficiency of the blastocyst
      transfer procedure was determined using control ewes > 150 days post-partum.
      Eight of nine recipient ewes established pregnancies and 75% of blastocysts
      survived to term. In Experiment 2, blastocysts were transferred to control (n =
      12) or post-partum (n = 10) recipients that had been induced to ovulate 28 days
      after lambing during the breeding season. Conceptus development was assessed 96 h
      after blastocyst transfer on Day 15 of the cycle. At this time, conceptus mass in
      the seven post-partum ewes which remained pregnant was generally lower than in
      the 11 corresponding control ewes. Conceptus and endometrial tissues were
      cultured separately for a further 24 h in vitro in the presence of [3H]leucine to
      determine production of oTP-1 and the pregnancy-specific endometrial protein p70
      respectively. Oxytocin binding sites were measured in endometrial tissue.
      Following 96 h culture in a post-partum uterus the conceptus retained its
      competence to synthesize and secrete ovine trophoblast protein 1 (oTP-1) in
      vitro. However, despite normal oTP-1 production the conceptus tissue failed to
      completely suppress endometrial oxytocin receptor binding. The negative
      correlation between p70 production and oxytocin receptor density implies a
      possible role for this protein in the suppression of oxytocin receptor synthesis
      required to prevent luteolysis in pregnant ewes.

PMID- 8265804
TI  - Oxidation of [U-14C]acetate by the sheep conceptus between days 13 and 19 of
      pregnancy.
AB  - Acetate metabolism by the sheep conceptus was assessed by measuring CO2
      production during a 2.5-h incubation of embryos and samples of the extraembryonic
      membranes in HEPES-buffered media containing 1.12 mM [U-14C]acetate. The rate of
      oxidation of acetate by embryonic tissue showed little change between Days 13 and
      15 of pregnancy but greatly decreased by Days 17 and 19. By contrast, oxidation
      of the substrate by the trophoblast increased substantially with development and
      was five times the early rate by Day 19. Oxidation of acetate by the yolk sac
      also increased 4-fold between Days 17 and 19. The addition of glucose to
      incubations of extraembryonic membranes resulted in some reduction in the
      oxidation of acetate by the yolk sac and allantois but had little effect on the
      trophoblast. At Days 13 and 15, the rate of oxidation of acetate by the embryonic
      disc was 6-7 times that by the trophoblast. As development progressed, this
      situation was reversed and by Day 19 the trophoblast metabolized more than five
      times the amount of acetate per microgram than did the Day-19 embryo. Although
      acetate metabolism by yolk sac and allantois on Day 17 was low, its metabolism by
      the yolk sac increased to values similar to those for the trophoblast at Day 19
      but its utilization by the allantoic membrane remained low. Comparison of the
      estimates of ATP generated from acetate by these tissue with those published for
      glucose demonstrates that acetate is much less effective than glucose for the
      provision of metabolic energy.

PMID- 8265805
TI  - Incorporation of substrate carbon from [U-14C]acetate by the sheep conceptus
      recovered from the uterus on days 13 to 19 of pregnancy.
AB  - Of the substrate carbon incorporated from 1.12 mM [U-14C]acetate as sole energy
      substrate during a 2.5-h incubation, a large proportion was isolated in the acid
      soluble fraction. Although there was no significant change over time in the rate
      of entry into this pool for embryos, the rate of accumulation by the trophoblast
      and yolk sac increased as development progressed. At Days 13 and 15 of pregnancy,
      incorporation of acetate into the acid-insoluble fraction of embryos accounted
      for almost half the total label accumulated. The rate of this incorporation fell
      rapidly over time and by Day 19 less than 30% of carbon accumulated was in this
      fraction. By contrast, the rate of incorporation into this fraction by
      trophoblastic tissue was low at Day 13 but rose dramatically as development
      progressed. Incorporation by the yolk sac into acid-insoluble components also
      rose with time. At the early stages of pregnancy studied, lipid synthesis
      accounted for the majority of acetate carbon accumulated by the conceptus in the
      acid-insoluble pool. At later stages of development, incorporation into lipids
      constituted a minor pool of acetate carbon. Some acetate carbon was found in the
      glycogen fraction of the conceptus. The rate of incorporation into the acid
      soluble glycogen fraction by embryos was constant throughout the period studied.
      By contrast, trophoblast increased its rate of incorporation markedly into both
      acid-soluble and acid-insoluble glycogen pools as did the yolk sac from Day
      17.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265806
TI  - No alpha-lactalbumin-like activity detected in a low molecular mass protein
      fraction of rat epididymal extract.
AB  - The same low M(r) protein fraction of epididymal luminal fluid as that studied
      previously by Hamilton in 1981 was assayed for alpha-lactalbumin (alpha-lac)
      activity with bovine milk galactosyltransferase (GalTase) as the enzyme source
      and bovine serum albumin (BSA) to make the total protein concentrations of all
      the samples in each assay constant. No alpha-lac activity could be detected in
      this fraction. When glucose was used as an acceptor, radioactivity passing
      through the ion exchange column used to retain the remaining UDP-galactose did
      increase with the amount of the proteins of the low M(r) fraction, but this
      increase was observed not only for samples with an acceptor but also for samples
      without. The increased radioactive product co-migrated in high-voltage
      electrophoresis with galactose, not lactose. When GlcNAc was used as an acceptor,
      the situation was the same, and the increased radioactive product co-migrated
      with galactose, not LacNAc. No inhibition of bovine milk GalTase activity by the
      low M(r) proteins was observed. Addition of protein, either BSA or the low M(r)
      fraction of epididymal luminal fluid, to assay medium that contained no proteins
      other than GalTase enhanced the GalTase activity both in forming lactose in the
      presence of glucose and also LacNAc in the presence of GlcNAc. It appears that
      the earlier reports of alpha-lac-like activity in epididymal fluids and extracts
      may have been due to the presence of enzymes liberating free galactose from UDP
      galactose and/or a stimulatory non-specific effect of the protein in the
      solutions on the lactose synthesis activity of the GalTase.

PMID- 8265807
TI  - Special issue: Insulin-like growth factors.

PMID- 8265808
TI  - Human hepatoma cells synthesize and secrete insulin-like growth factor Ia
      prohormone under growth hormone control.
AB  - Nucleotide sequencing of cDNAs encoding human insulin-like growth factor I (IGF
      I) predicts the existence of two different prohormone forms of IGF-I. The E
      peptide regions extend the carboxy-terminus of the 70 amino acid core IGF-I
      molecule (BCAD domains) by either an additional 35 (IGF-Ia) or 77 (IGF-Ib) amino
      acids. Employing antiserum directed against a peptide sequence unique to the E
      peptide region of IGF-Ia prohormone, we have identified EIa immunoreactive
      material (IR-EIa) in the conditioned medium of a human hepatoma cell line, HepG2.
      Human growth hormone (GH) had dose-dependent stimulatory effects on IR-EIa
      secretion; incubation of HepG2 cells with GH at maximal concentrations (1-5
      micrograms/ml) increased specific IR-EIa in 24 h conditioned medium 3-fold. The
      addition of human placental lactogen, insulin, IGF-I, dexamethasone, beta
      estradiol, or progesterone had no significant effect. Acid chromatography of
      HepG2 cell conditioned medium revealed a single elution peak of IR-EIa
      corresponding to M(r) = 12,000-20,000. There was no immunologically detectable
      7500 M(r) IGF-I peptide in acid-chromatographed conditioned medium under either
      basal or stimulated conditions. Biosynthetic labelling of HepG2 cell products
      with [35S]Trans label and immunoprecipitation with antisera specific to the E or
      to the AD regions of the IGF-Ia molecule indicated a single species of approx.
      14,000 M(r). These data indicate that the E peptide region of IGF-Ia is
      translated and released as part of the larger molecule in cultured HepG2 cells,
      and that the levels of this prohormone are regulated by GH.

PMID- 8265809
TI  - Fluoxetine induced insulin-like growth factor II (IGF-II) changes in hypothalami
      of normal, exercised and food restricted rats.
AB  - Hypothalamic and pituitary insulin-like growth factor II (IGF-II) peptide
      concentrations are differentially regulated by factors associated with metabolism
      such as insulin and glucoprivation. However, the effects of other metabolic
      stressors such as food restriction or exercise on hypothalamic IGF-II
      concentrations remain largely to be explored. In order to assess whether
      metabolic stress alters central nervous system IGF-II secretion, peptide analysis
      was conducted in rats exhibiting activity-based anorexia (ABA) compared to
      exercised-matched, body weight-matched or ad libitum fed controls. Further, the
      possibility of serotonergic control of IGF-II secretion was examined by
      determining IGF-II response to fluoxetine (FLX) injections (15 mg/kg body wt.,
      i.p.). While ABA and body weight loss altered peripheral IGF-II concentrations
      compared to ad libitum fed or exercised controls, these treatments had no effect
      on hypothalamic or posterior pituitary IGF-II content. However, FLX
      administration increased IGF-II concentrations in the ventromedial hypothalamus
      and decreased IGF-II content in the lateral hypothalamus compared to vehicle
      injected. Anterior pituitary levels of IGF-II were also decreased by FLX. These
      data suggest that a serotonergic influence on CNS IGF-II exists and that IGF-II
      secretion may be altered by factors affecting serotonin metabolism or efficacy.

PMID- 8265810
TI  - Effects of serum and insulin-like growth factors on human neuroblastoma cell
      growth.
AB  - Insulin-like growth factors (IGF-I and IGF-II) are mitogenic polypeptides
      expressed in both developing and adult tissues. To examine the effects of IGFs on
      neuronal growth, we used SH-SY5Y neuroblastoma cells as an in vitro model of
      nervous system development. In the current study, we found that either IGF-I (0.1
      to 10 nM), insulin (0.1 to 5 micrograms/ml) or calf serum (0.1 to 3%) increased
      SH-SY5Y proliferation over a 3 day period in a dose dependent manner. In each
      case, treatment with anti-IGF-I receptor antibodies blocked cell proliferation.
      IGF-II mRNA levels correlated with SH-SY5Y cell density; subconfluent cells
      expressed high levels of IGF-II mRNA while low levels of IGF-II mRNA were present
      in confluent cells. Similarly, serum deprivation increased IGF-I receptor mRNA by
      4-fold. Collectively, these results support the concept that an IGF/IGF-I
      receptor system at least partially mediates SH-SY5Y cell proliferation and
      suggests the importance of IGFs in regulating neuronal growth.

PMID- 8265811
TI  - IGF receptor function and regulation in autocrine human neuroblastoma cell
      growth.
AB  - Insulin-like growth factor-II (IGF-II) and its receptors (type I and II IGF
      receptors) are expressed in the nervous system in a tissue and developmentally
      specific manner. We have previously shown that SH-SY5Y human neuroblastoma cells
      synthesize and secrete high levels of IGF-II, and respond to it with increased
      neuritic outgrowth, DNA synthesis, and cell proliferation. SH-SY5Y cells also
      produce type I IGF and IGF-II/M6P receptors; however, it is not known whether
      these receptors mediate the observed growth promoting effects of IGF-II. In this
      study, we assayed the role of type I IGF receptor and IGF-II/M6P receptor
      expression in mediating autocrine IGF-II induced growth. Using anti-receptor
      antibodies, we found that IGF-II stimulates cell proliferation via the type I IGF
      receptor but not via the IGF-II/M6P receptor. By Northern analysis, we detected
      increased mRNA expression of both receptors, with more dramatic changes in type I
      IGF receptor expression. Collectively, our results indicate a role for the type I
      IGF receptor in mediating IGF-II induced autocrine neuroblastoma cell growth.

PMID- 8265812
TI  - Modulation of insulin like growth factor I (IGF-I) binding sites on erythrocytes
      by IGF-I treatment in patients with Laron syndrome (LS).
AB  - The in vivo regulation of IGF-I binding sites was evaluated using erythrocytes
      (RBC) from 8 patients with Laron syndrome (LS), before and after IGF-I treatment
      (120-150 micrograms/kg/day s.c.). Basal fasting IGF-I averaged 20.48 +/- 2.06
      nmol/l (mean +/- S.E.M.) in the control group as compared to 4.72 +/- 0.84 nmol/l
      in the 8 LS patients (P = 0.0001). After 1 week of IGF-I treatment serum IGF-I
      levels increased to 6.53 +/- 1.58 nmol/l (a mean difference of 1.81 +/- 0.95, P =
      0.05) and after 1 month of treatment to 14.37 +/- 4.56 nmol/l (a mean difference
      of 9.37 +/- 4.42, P = 0.03). Concomitantly, we found a significant decrease in
      the number of high affinity IGF-I binding sites, from 5.74 +/- 0.86 sites/cell
      (mean +/- S.E.M.) in the non-treated state to 2.29 +/- 0.64 sites/cell and 2.17
      +/- 0.53 sites/cell after 1 week and 1 month of treatment, respectively (a mean
      difference of -3.44 +/- 0.94, P = 0.004 and -3.58 +/- 0.79, P = 0.002,
      respectively), values similar to those found in the control group. These data
      demonstrate that replacement treatment of LS patients with IGF-I down regulates
      its specific receptors. We propose IGF-I binding to RBC as a test to determine
      the responsiveness of patients considered for long term IGF-I treatment.

PMID- 8265813
TI  - Effects of growth hormone and IGF-I on glomerular ultrafiltration in growth
      hormone-deficient rats.
AB  - In growth hormone deficient states glomerular filtration rate (GFR) and renal
      plasma flow rate (RPF) are both reduced. Studies were performed in growth hormone
      deficient rats to delineate the physiologic mechanisms by which growth hormone
      and IGF-I contribute to the regulation of glomerular function. Growth hormone
      deficient dw/dw rats received, for one week, subcutaneous infusions of vehicle,
      des(1-3)IGF-I or were injected i.m. with recombinant human growth hormone.
      Subsequent renal micropuncture and clearance studies revealed a low GFR and
      single nephron GFR (SNGFR) in vehicle treated growth hormone deficient animals.
      Glomerular function became normal with growth hormone or IGF-I treatment,
      respectively. Both treatments raised SNGFR by reducing arteriolar resistance and
      increasing the glomerular ultrafiltration coefficient. Furthermore, the two
      treatments also increased the glomerular tuft volume and the kidney weight which
      may contribute to the rise in SNGFR and GFR. It is concluded that, (1) in growth
      hormone deficiency glomerular function is reduced secondary to a high renal
      arteriolar resistance and a low ultrafiltration coefficient. Both result from a
      lack in IGF-I rather than the growth hormone deficiency state per se. (2) The
      growth hormone-IGF-I axis may contribute to the maintenance and physiologic
      regulation of GFR.

PMID- 8265814
TI  - Identification of insulin-like growth factor (IGF) and glucose transporter-1 and 
      3 mRNA in CNS tumors.
AB  - Glucose metabolism is increased in CNS tumors and correlates with malignant
      grade. We have previously investigated the role of IGFs in regulating CNS tumor
      growth and metabolism. In the present study we examined total cellular RNA from
      human CNS tumors for the presence for glucose transporter (Glut) and IGF mRNA.
      Human meningiomas and gliomas were frozen in liquid nitrogen at the time of
      surgery and then stored at -80 degrees C. Total cellular RNA was prepared by acid
      guanidinium phenol-chloroform extraction and 20 micrograms of RNA was loaded for
      agarose-formaldehyde gel electrophoresis and transfer. RNA integrity in 5
      meningiomas and 2 gliomas was confirmed by ethidium bromide staining of 28S and
      18S ribosomal RNA and hybridization with a cDNA probe for beta-actin. For
      analysis, membranes were hybridized to radioactively labeled human Glut-1, Glut
      3, IGF-I, and IGF-II cDNA probes, and mRNA transcripts were identified by
      autoradiography. All 7 tumors expressed Glut-1 and Glut-3 mRNA and Glut-3
      appeared to be more abundant in meningiomas. IGF-II mRNA was detected in 2 of 6
      meningiomas and in both gliomas. IGFs may play an important role in the
      regulation of glucose metabolism in CNS tumors. IGFs and specific glucose
      transporters may prove useful as markers of malignancy and potential targets for
      future therapy.

PMID- 8265815
TI  - Evidence for two insulin-like growth factor I receptors with distinct primary
      structure that are differentially expressed during development.
AB  - We have previously presented evidence for two IGF I receptor species in rat
      skeletal muscle. One form of IGF I receptor is selectively expressed in fetal and
      early postnatal life, and the second is present in both fetal and adult animals.
      These two IGF I receptors were shown to have similar tryptic phosphopeptide maps
      but to differ in beta subunit molecular weight (105,000 for the fetal vs. 95,000
      for the adult type receptor). In this study, we have used specific antibodies to
      investigate the structural relationships between the two IGF I receptors. Anti
      IGF I receptor beta subunit antibodies were generated against synthetic peptides
      corresponding to residues 1284-1293 and 1308-1318 of the cloned human IGF I
      receptor, and the capacity of these antibodies to interact with the two IGF I
      receptors was investigated. Both anti-peptide antibodies selectively
      immunoprecipitated the higher molecular weight fetal receptor and not the adult
      receptor from rat muscle. Human placenta and muscle were shown to contain two
      receptors similar to those observed in rat muscle. In human muscle, the anti
      peptide antibodies and the human-specific monoclonal alpha subunit antibody alpha
      IR3 also selectively immunoprecipitated the fetal type receptor. The presence of
      a 95,000 M(r) IGF I receptor beta subunit distinct from the insulin receptor beta
      subunit in human muscle was confirmed by the demonstration of an IGF I sensitive
      receptor with a beta subunit of this size after insulin receptor immunodepletion.
      These data strongly support the conclusion that the fetal and adult type IGF I
      receptors differ in primary structure. The fetal receptor corresponds to the
      cloned and sequenced IGF I receptor, and the primary structure of the adult type
      receptor has not yet been established.

PMID- 8265816
TI  - Human IM-9 lymphoblasts as a model of the growth hormone-insulin-like growth
      factor axis: gene expression, and interactions of ligands with receptors and
      binding proteins.
AB  - Human IM-9 lymphoblasts bind growth hormone (hGH) and insulin-like growth factors
      (IGFs). We have systematically examined the IM-9 cells as a valuable model of the
      interaction of hGH and the IGFs at the cellular level. Cells were cultured in
      medium with 10% serum and for a subset of experiments cultured in serum-free
      medium. Binding of [125I]hGH and [125I]IGF-I and -II to intact IM-9 cells was
      measured: unlabeled hGH inhibited binding of [125I]hGH (half max. 20 ng/ml).
      Binding of [125I]IGF-I was inhibited by IGF-I (half max. 7.5 ng/ml), IGF-II (half
      max. 60 ng/ml), and insulin and anti IGF-I receptor antibody (alpha IR3).
      [125I]IGF-II was inhibited by IGF-II (half max. 15 ng/ml), IGF-I (half max. 500
      ng/ml), insulin (half max. 250 ng/ml) but not by alpha IR3. Crosslinking
      experiments with [125I]IGF-II and DSS as the crosslinking agent and analysis of
      radioligand-receptor complexes by SDS-PAGE under reducing conditions revealed
      that [125I]IGF-II bound to a 250 kDa and a 135 kDa receptor species. The latter
      possibly represents an insulin-type receptor whereas the 250 kDa species had the
      characteristics of the IGF-II/M6P receptor. When IM-9 cell conditioned medium was
      analyzed in ligand blotting experiments with either [125I]IGF-I or -II a 30 kDa
      IGFBP species was detected on the autoradiographs. Also, IGF-II immunoreactivity
      (approx. 1 ng/ml medium) was measured in the cell conditioned medium using an IGF
      BP blocked RIA employing [125I]IGF-II. In a subset of experiments IM-9 cells were
      homogenized in 4 M guanidinium-thiocyanate and RNA extracted in 5.7 M CsCl.
      Denatured RNA was electrophoresed on 0.8% agarose gels and transferred to a nylon
      membrane, fixed and the blots hybridized with cDNA probes. Probes were labeled
      with [32P]dCTP using a random prime labeling procedure: a Pst I 700 bp fragment
      of the human IGF-I cDNA, a 554 bp Pst I-Sal I fragment of the IGF-II cDNA, a 614
      bp Pst I fragment of the IGF-I receptor cDNA and a 663 bp Pst I fragment of the
      IGF-II/M6P receptor. Autoradiographs of Northern blots showed specific
      hybridization with the IGF-I probe at 3.7 kb and with the IGF-II probe at 5.3 kb.
      No signal was detected with the IGF-I receptor cDNA probe. Hybridization with the
      IGF-II/M6P receptor probe yielded a 9 kb RNA species.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8265817
TI  - Insulin II gene expression in rat central nervous system.
AB  - Controversy persists concerning the origin of insulin in the central nervous
      system. While there has been convincing evidence in vitro to demonstrate the
      presence of neuronal insulin mRNA, conventional assays have failed to detect the
      same in whole brain preparations. Here we employed RNAse-protection and sensitive
      reverse transcription-polymerase chain reaction (RT-PCR) assays in attempts to
      detect insulin I and II mRNAs in rat brains obtained from different developmental
      stages. The RNAse-protection assay did not detect insulin I or insulin II
      transcripts in fetal (13 to 21 day gestation) or adult brains. RT-PCR, while
      detecting low amounts of insulin I transcripts in other extrapancreatic tissues
      such as the rat yolk sac and fetal liver previously shown to express insulin II,
      failed to detect insulin I in brain at any age examined. Insulin II mRNA was
      detected by RT-PCR in fetal, neonatal and adult rat brains, just as in yolk sac,
      fetal and adult livers. We conclude that while the duplicated insulin I gene is
      not expressed, the ancestral insulin II gene is expressed in fetal, neonatal and
      adult rat brains. Our observations support the concept of de novo brain insulin
      II synthesis beyond the pre-pancreatic stage of embryonic development.

PMID- 8265818
TI  - The branching of insulin-like growth factor 1 and insulin: an immunohistochemical
      analysis during phylogeny.
AB  - The co-existence of insulin-like growth factor 1 (IGF-1) with the classical islet
      hormones insulin (INS), glucagon (GLUC), somatostatin (SOM) and pancreatic
      polypeptide (PP) in the endocrine pancreas of representative species of
      cyclostomes (Myxine glutinosa), cartilaginous fish (Raja clavata, Squalus
      acanthias) and bony fish (Cottus scorpius, Carassius auratus, Cyprinus carpio,
      Anguilla anguilla) was studied by the use of monoclonal and polyclonal antisera
      and the double immunofluorescence technique. In all species investigated, IGF-1
      like-immunoreactive cells were found in the endocrine pancreas, however, in
      varying localization. In Myxine glutinosa, all INS-immunoreactive cells and some
      of the SOM-immunoreactive cells contained IGF-1-like-immunoreactivity. In Raja
      and Squalus, only a minority of the INS-immunoreactive cells also displayed IGF-1
      like-immunoreactivity. The majority of the IGF-1-like-immunoreactivity was
      observed in SOM- and in GLUC-immunoreactive cells. Different results were
      obtained in bony fish. In Cottus, in the Brockmann bodies and the small islets
      IGF-1-like- and INS-immunoreactivities co-existed to 100%. In contrast, in the
      other bony fish studied IGF-1-like-immunoreactivity was not observed in INS
      immunoreactive cells: in Cyprinus, IGF-1-like-immunoreactivity was found in GLUC
      , PP- and SOM-immunoreactive cells and in Carassius and Anguilla, in SOM
      immunoreactive cells only. Thus, in all bony fish species with the exception of
      Cottus, IGF-1 and insulin display a distinct cellular distribution, similar to
      that of mammals. The present results, thus, may indicate that the branching of
      IGF-1 and insulin has occurred at the phylogenetic level of bony fish.

PMID- 8265819
TI  - Differential expression of the human, mouse and rat IGF-II genes.
AB  - The IGF-II gene is a complex transcription unit. Multiple transcripts are
      synthesized as a result of alternate promoter usage and the splicing of unique 5'
      untranslated regions to common coding exons. In order to characterize the
      mechanisms of IGF-II gene regulation we performed comparative studies to define
      essential features of IGF-II expression in human, rat and mouse. Homologous
      promoter regions of the human, mouse and rat IGF-II genes were fused to the
      luciferase reporter gene and expression was measured in various cell lines that
      have an endogenously active or inactive IGF-II gene expression pattern,
      respectively. The transient promoter activity of the human, mouse and rat IGF-II
      constructs was further compared with the endogenous activity of the IGF-II gene
      in various tissues and cell lines of human, mouse and rat origin. The results
      indicate that in transient expression assays employing heterologous systems
      (e.g., mouse promoter in human cells), most IGF-II promoter constructs are
      active, albeit at low levels. Maximal promoter activity is only observed,
      however, in homologous systems (e.g., human promoter constructs tested in human
      cells). This suggests that each promoter, despite the strong sequence
      conservation of the homologous human, rat and mouse promoters, is adapted to the
      levels of the transcription factors present in its natural environment. Finally,
      IGF-II gene expression is not only regulated at the level of transcription but
      also depends on mRNA stability. We show that human, rat and also mouse IGF-II
      mRNAs are subjected to specific endonucleolytic cleavage, suggesting that
      specific cleavage of IGF-II mRNAs must be of general physiological importance.

PMID- 8265820
TI  - Characterization of type I IGF receptor and IGF-I mRNA expression in cultured
      human and bovine glomerular cells.
AB  - Glomerular hypertrophy is reported in several endocrine disorders such as
      acromegaly and diabetes mellitus, where abnormalities of growth hormone and
      insulin-like growth factor (IGF-I) have been reported. In the present report, we
      have cultured bovine and human glomerular endothelial cells, and bovine
      glomerular epithelial and mesangial cells, and characterized the expression of
      IGF-I mRNA and its receptor in these cells. High affinity, specific receptors for
      IGF-I were identified in all three types of cells by radioreceptor assays.
      Receptor number (Ro) derived by Scatchard analysis revealed an unusually high
      number of Type I IGF receptors, approx. 1.2 x 10(5) receptors/cell in glomerular
      endothelial cells. Affinity crosslinking studies and immunoprecipitation with
      antibodies against the Type I IGF receptor identified the alpha-subunit of the
      IGF-I receptor as having a molecular mass of 140 kDa. Biologically, IGF-I was
      more potent than insulin or IGF-II in stimulating DNA synthesis in glomerular
      endothelial cells. Northern blot analysis showed that glomerular and aortic
      endothelial cells expressed IGF-1 mRNA of 1.7 kb. In contrast, renal glomeruli
      showed several IGF-1 mRNAs of 7.5, 1.7 and 1.2 kb. Thus, the demonstration of
      both a prepondence of Type I IGF receptors coupled with the growth promoting
      effects of IGF-I in glomerular endothelial and epithelial cells, as well as the
      local production of IGF-I mRNA suggests that IGF-I serves an important role as an
      autocrine or paracrine regulator of the growth of renal glomeruli.

PMID- 8265822
TI  - Evaluation of the brain by positron emission tomography.
AB  - Positron emission tomography (PET) is a nuclear medicine imaging technique for
      performing regional physiologic measurements in vivo. This article reviews the
      basic principles of PET as applied to the study of the brain, the components of
      PET are described, including instrumentation, radiotracers, mathematical models
      for calculating physiologic parameters, and methods to analyze PET data. There is
      special emphasis on the most commonly used methods: those to measure regional
      cerebral blood flow and metabolism. The interpretation of abnormalities of
      cerebral blood flow and metabolism is discussed and related to possible
      pathophysiologic mechanisms of central nervous system involvements in systemic
      lupus erythematosus.

PMID- 8265821
TI  - Regulation of endometrial cancer cell growth by insulin-like growth factors and
      the luteinizing hormone-releasing hormone antagonist SB-75.
AB  - The involvement of IGFs in growth regulation of the Ishikawa endometrial tumor
      cell line and the possible interference of LH-RH analogues with a potential
      autocrine or paracrine loop involving IGFs was evaluated. The mitogenic effects
      of IGF-I, IGF-II, and insulin were compared. IGF-I was found to be 3-fold more
      potent than IGF-II and 30-fold more potent than insulin, suggesting that the
      effects of these growth factors are mediated by the IGF-I receptor. Ishikawa
      endometrial cancer cells secrete IGF-II, but not IGF-I, and insulin (1 microM)
      stimulates IGF-II release. The LH-RH antagonist [Ac-D-Nal(2)1, D-Phe(4Cl)2, D
      Pal(3)3, D-Cit6, D-Ala10]-GnRH (SB-75, CETRORELIX) inhibited basal and IGF
      induced growth. Moreover, this antagonist almost completely inhibited IGF-II
      release from Ishikawa cells, while having no significant effect on the number or
      affinity of IGF-I binding sites. Inhibition of IGF-II release occurred at a lower
      SB-75 concentration than that needed for a reduction in cell number. The ED50 of
      SB-75 for IGF-II release was 0.3 microM as compared to 1.5 microns concentration
      which is required for reduction in cell number, suggesting that inhibition of
      growth factor release precedes cell growth inhibition. We conclude that the LH-RH
      antagonist SB-75 can inhibit the growth of endometrial cancer cells by
      interfering with the autocrine action of IGF-II and also by directly inhibiting
      the growth-stimulatory effects of IGFs, probably through effects on a post
      receptor mechanism.

PMID- 8265823
TI  - Dilemmas in neuropsychiatric lupus.
AB  - It is estimated that two thirds of neuropsychiatric (NP) manifestations in lupus
      are not directly related to active NP lupus but instead are a consequence of
      secondary causes such as drugs, infections, and hypertensive and metabolic
      complications in the setting of systemic lupus erythematosus (SLE). It is often
      difficult to distinguish clinically between primary central nervous system lupus
      and secondary causes of NP manifestations. In general, NPSLE has been reported to
      be a prognostic factor for a poor long-term outcome in lupus. Despite early
      recognition of the disease and aggressive therapeutic interventions, it is still
      frequently associated with increased mortality.

PMID- 8265824
TI  - Cognitive deficits in systemic lupus erythematosus.
AB  - Several independent studies have now demonstrated the presence of significant
      cognitive impairment in SLE patients. Such impairment, whether it precedes or
      follows overt NP events, suggests compromise of the neural substrate,
      irrespective of overt clinical NP symptomatology. The association between
      cognitive impairment and brain cross-reactive autoantibodies suggests one
      mechanism for CNS involvement in SLE that warrants further study; the data
      relating specific cognitive deficits to the presence of specific antibodies raise
      the intriguing possibility of system- or structure-specific immune-mediated
      involvement in the CNS. Whatever the mechanism, cognitive impairment in SLE may
      have significant implications for daily functioning of some lupus patients and
      requires the selection of appropriate psychosocial and somatic treatment
      strategies.

PMID- 8265825
TI  - Neurologic complications of antiphospholipid antibodies.
AB  - Antibodies directed against phospholipids are highly associated with venous and
      arterial thrombotic episodes, which are often recurrent. There seems to be a
      skewed frequency of cerebral and ocular events when the arterial circulation is
      affected. Other neurologic syndromes, including dementia, migraine, chorea,
      transverse myelopathy, Guillain Barre syndrome, transient global amnesia,
      seizures, motor neuron disease, myasthenia gravis, and depression, have also been
      described in association with aPL. Although some of them (for example, dementia,
      chorea, seizures, and transient global amnesia) could well be the result of aPL
      related cerebrovascular disease, the relationship of aPL to the underlying
      pathophysiology of these syndromes is less clear. Clues that should lead one to
      consider evaluating for these antibodies include recurrent thrombosis (especially
      in young people), recurrent fetal loss, and thrombocytopenia. Associated
      laboratory abnormalities may include a biologically false-positive VDRL test,
      abnormal ANA or anti-DNA titers, and a high ESR. If the APTT is positive on
      routine screening and does not correct with mixing studies, a LA should be highly
      suspected. More sensitive and specific tests are usually necessary to detect aPL,
      however. Many in vitro and, more recently, in vivo systems strongly suggest that
      aPL may be directly implicated in the pathogenesis of thrombosis, as opposed to
      being markers of a procoagulant state. The management of patients with aPL
      associated thrombosis can be difficult. Prospective studies are needed to
      determine the optimal treatment strategies for this group of patients.

PMID- 8265826
TI  - Magnetic resonance spectroscopy and positron emission tomography scanning in
      neuropsychiatric systemic lupus erythematosus.
AB  - Nuclear magnetic resonance spectroscopy (MRS) and positron emission tomography
      (PET) scanning are the only two non-invasive methods available for obtaining
      metabolic data on inaccessible tissues such as the brain. MRS and PET scanning
      are powerful research techniques that provide strong evidence that
      neuropsychiatric lupus is a brain disorder characterized by profound metabolic
      alterations including impaired blood flow, ischemia, decreased aerobic
      metabolism, and progressive neuronal loss.

PMID- 8265827
TI  - Neurologic disease in Sjogren's syndrome: mononuclear inflammatory vasculopathy
      affecting central/peripheral nervous system and muscle. A clinical review and
      update of immunopathogenesis.
AB  - There is a growing appreciation that a subset of patients with primary Sjogren's
      syndrome (SS) also may develop a spectrum of central nervous system (CNS)
      complications. This article defines SS and its significance; discusses CNS,
      peripheral nervous system, and muscular complications of SS; identifies those
      areas in general or internal medicine in which SS patients with potential
      neurologic complications may present; describes those neurologic disorders that
      SS may mimic; places into perspective the controversy regarding the frequency and
      significance of CNS-SS; and extends our observations on the immunopathogenesis of
      neurologic complications in SS.

PMID- 8265828
TI  - Is central nervous system involvement a systemic manifestation of primary
      Sjogren's syndrome?
AB  - Central nervous system involvement in primary Sjogren's syndrome (pSS) is a
      controversial issue. Without an international criteria for the diagnosis of pSS,
      each research center must establish, publish, and strictly adhere to their own
      criteria. Therefore, patients should be made aware of professional uncertainties,
      particularly when therapeutic decisions are involved.

PMID- 8265829
TI  - Neurologic manifestations of systemic vasculitides.
AB  - Involvement of the nervous system is frequently observed in patients with
      vasculitis. Peripheral neuropathy is often an early and dominating feature of the
      disease process. Cranial nerve palsy, central nervous system vasculitis, and
      inflammatory myopathy are other neurologic manifestations.

PMID- 8265830
TI  - Neurologic aspects of giant cell (temporal) arteritis.
AB  - Headache is the most frequent symptom for which a patient with giant cell
      arteritis (GCA) presents to a neurologist. Amaurosis fugax and ischemic optic
      neuropathy are well-recognized complications. Less commonly recognized neurologic
      complications include transient ischemic attacks, cerebral infarctions, acute
      confusional states (due to multi-infarct dementia), ischemic cervical myelopathy,
      and ischemic mononeuropathies. Because patients with GCA generally respond well
      to corticosteroid therapy, prompt diagnosis can minimize neurologic damage.

PMID- 8265831
TI  - Neurologic complications of rheumatoid arthritis.
AB  - Neurologic complications are common extraarticular manifestations of RA,
      involving both the peripheral and central nervous systems. Because RA patients
      suffer from pain, stiffness, and weakness, the detection of neurologic impairment
      is often difficult. Thus, close vigilance and thoughtful use of various
      diagnostic methods will help in the early diagnosis of cervical spine
      involvement, compression neuropathies, peripheral neuropathies, myopathies, and
      central nervous system involvement. Prompt and timely interventions may prevent
      permanent neurologic sequelae.

PMID- 8265832
TI  - Sensory neuropeptides and rheumatic diseases.
AB  - Sensory peptides are involved not only in neurotransmission and neuromodulation
      but also in the local control of immune function, vascular tone, and cellular
      proliferation. It appears that different activities of these neuropeptides are
      mediated by specific receptors on immune and nonimmune cells. The purpose of this
      article is to discuss what is known of the main sensory neuropeptides and to
      speculate on their possible pathophysiologic role in joint (rheumatoid arthritis)
      and connective tissue diseases (systemic sclerosis).

PMID- 8265833
TI  - Neurologic complications of Lyme disease.
AB  - Lyme disease is now the most frequent vector-borne infection in the United
      States. It is due to a spirochete, Borrelia burgdorferi, which is inoculated into
      the host by the bite of an infected Ixodes (hard body) tick. The nervous system
      is frequently involved in clinical infections, with characteristic central and
      peripheral nervous system syndromes. The diagnosis and treatment of neurologic
      Lyme disease, however, can pose certain problems. Lyme disease should be included
      in the differential diagnosis of most major neurologic syndromes.

PMID- 8265834
TI  - Single lung transplantation for emphysematous disease.

PMID- 8265835
TI  - A computer system for a respiratory medicine department.

PMID- 8265836
TI  - Allergic alveolitis: new insights into old mysteries.

PMID- 8265837
TI  - Sleep and the lung: current issues in nocturnal respiratory research.

PMID- 8265838
TI  - A large Q fever outbreak in the West Midlands: clinical aspects.
AB  - In the spring of 1989 the largest outbreak of acute Q fever recorded in the
      United Kingdom occurred in Solihull and surrounding areas of the West Midlands.
      The diagnosis was confirmed in 147 people, mainly males of working age. Windborne
      spread from farmland to the south of the urban area was the most likely route of
      infection. Fever was the commonest symptom, seen in 101/102 (99%) cases, followed
      by weight loss reported by 83/101 (82%). Headache, often severe, was experienced
      by 69/101 (68%). The commonest respiratory symptom was breathlessness, 65/102
      (64%), followed by cough, 52/102 (51%), and chest pain, 46/102 (45%).
      Neurological features, seen in 23% of cases, were more prominent in this outbreak
      than is commonly recognized. Persisting ill health 6 months following the acute
      episode not due to chronic Q fever was also a prominent feature of this largely
      urban outbreak.

PMID- 8265839
TI  - Nedocromil sodium and sodium cromoglycate in patients aged over 50 years with
      asthma.
AB  - We conducted a double-blind parallel-group study to compare the efficacy of
      inhaled nedocromil sodium and inhaled sodium cromogylcate in patients aged 50
      years or over with asthma. Seventy-seven patients were randomized, 38 to receive
      nedocromil sodium (4 mg q.d.s.) and 39 to receive sodium cromoglycate (10 mg
      q.d.s.) over a 16-week period. Eight patients withdrew from the study. Both
      patient groups showed a reduction in inhaled bronchodilator usage during the
      treatment period. No statistically significant differences were seen in diary
      card PEF recordings or symptom scores. Both clinic PEF and FEV1 were
      significantly greater (P < 0.05) in the sodium cromoglycate group at week 12.
      Patients considered the treatment to be very or moderately effective in 59% of
      the nedocromil sodium group and 50% of the sodium cromoglycate group. Thus, the
      study suggests that there is no difference in response to nedocromil sodium or
      sodium cromoglycate in this older group of patients with asthma who are already
      on moderate doses of inhaled steroids.

PMID- 8265841
TI  - Spontaneous pneumothorax in paediatric patients.
AB  - To obtain information to guide the management of children and early adolescents
      with apparent spontaneous pneumothorax the medical records of all patients over
      the age of 5 years presenting with this condition over a 25-yr period were
      reviewed. Twelve patients had a pneumothorax not associated with an acute episode
      of asthma. Six of these underwent thoracotomy at first presentation. Of the six
      who were initially treated conservatively five had a recurrence on the
      ipsilateral side. Seven patients developed a pneumothorax during an acute episode
      of asthma and none had a recurrence. Early intervention by either thoracotomy or
      some form of closed pleurodesis should be considered in paediatric patients
      presenting with an apparent spontaneous pneumothorax not associated with an acute
      episode of asthma. Pneumothorax complicating an acute episode of asthma is rare
      in the paediatric age group and is unlikely to recur.

PMID- 8265840
TI  - DNA amplification by the polymerase chain reaction to detect sub-clinical
      Pneumocystis carinii colonization in HIV-positive and HIV-negative male
      homosexuals with and without respiratory symptoms.
AB  - Pneumocystis carinii colonization was studied in 90 men using the polymerase
      chain reaction. These comprised ten heterosexual controls; ten HIV-seronegative
      homosexual controls; 20 HIV-seropositive homosexuals with blood CD4 count > 400 x
      10(6) l-1; 20 HIV-seropositive homosexuals with CD4 < 400 x 10(6) l-1; ten HIV
      seropositive homosexuals with CD4 < 60 x 10(6) l-1 receiving PCP
      chemoprophylaxis; and 20 HIV-seropositive homosexuals with respiratory symptoms
      but without PCP. Induced sputum was obtained from all but the last group, who had
      bronchoalveolar lavage, and all specimens were tested for P. carinii using the
      polymerase chain reaction. The first four groups received no pneumocystis
      chemoprophylaxis, and all but the last group were asymptomatic. P. carinii
      colonization did not occur in the two control groups. P. carinii colonization
      rates were significantly different in the CD4 > 400, CD4 < 400, and CD4 < 60
      groups (10%, 20%, and 40% respectively) (P < 0.025). Two patients (one each from
      CD4 < 400 and CD4 < 60) developed PCP 4-6 weeks after sputum induction, both had
      previously had high levels of P. carinii on sputum induction. Two patients from
      the CD4 < 400 group had high levels of P. carinii but did not develop PCP. In the
      symptomatic group, two subjects had low levels of P. carinii, but did not develop
      PCP. We have demonstrated P. carinii colonization in HIV-seropositive homosexuals
      in association with a low peripheral CD4 count. The polymerase chain reaction may
      be a useful technique for determining the need and efficacy of anti-pneumocystis
      chemoprophylaxis.

PMID- 8265842
TI  - Cystic fibrosis: antibiotic prescribing practices in the United Kingdom and Eire.
AB  - The antimicrobial prescribing practices of 26 physicians from the U.K. and Eire
      who care for patients with cystic fibrosis (CF) were assessed by postal
      questionnaire. Our main aim was to delineate divergent practices which may reveal
      a need for controlled prospective studies. For first-line intravenous (i.v.)
      therapy of acute exacerbations associated with Pseudomonas aeruginosa, 20
      physicians (76.9%) combine a penicillin derivative with an aminoglycoside, in
      contrast to five (19.2%) who regularly use i.v. monotherapy with ceftazidime and
      one who combines i.v. ceftazidime with an aminoglycoside. When i.v. therapy is
      considered inappropriate, oral ciprofloxacin is sometimes used by all clinicians
      and oral broad spectrum agents are used in addition by 13, chloramphenicol being
      prescribed most often. Excluding allergy, the most important factor influencing
      choice of agents by 19 (73.1%) physicians is the most recent sputum
      susceptibility results. For maintenance therapy, 21 prescribe oral anti
      staphylococcal agents if Staphylococcus aureus is isolated; of these, eight do so
      only if lung function deteriorates, nine after repeated isolation and four after
      first isolation of S. aureus. The remaining five physicians give anti
      staphylococcal drugs to all patients once the diagnosis of CF is made. For
      maintenance of lung function in patients with persistent P. aeruginosa, all
      physicians used nebulized antibiotics, the indications for which vary between
      units. There was general concordance in the therapy of exacerbations associated
      with P. aeruginosa, whereas the use of agents to maintain lung function is more
      varied. We suggest that prospective studies address practices which vary greatly,
      such as the route, the duration and the timing of initiating antibiotic therapy
      given to maintain lung function.

PMID- 8265843
TI  - Endurance exercise capacity in adults with cystic fibrosis.
AB  - We have compared the maximal and endurance exercise capacities in 22 (15 male)
      adult cystic fibrosis (CF) patients with a resting oxygen saturation (SaO2) > or
      = 90%, with age and sex matched controls (CON). The maximum oxygen uptake
      (VO2max) and heart-rate were lower for the CF group whereas the maximum
      ventilation reached a higher percentage of predicted. Furthermore, for the CF
      group there was a relationship between the % predicted VO2max and measures of
      lung function, confirming a ventilatory limit to maximum exercise in patients
      with more severe disease and a near normal maximum exercise capacity in those
      with mild disease. Endurance capacity, defined as the duration of exercise at 80%
      of each individuals VO2max, was however similar for the two groups [CF: 22.21
      (15.82) vs. CON: 24.94 (13.05) min]; despite the CF group exercising under less
      efficient ventilatory conditions. Endurance capacity was not related to the
      measurements of lung function. Of the seven CF patients desaturating at maximal
      exercise (SaO2 < 90%), five desaturated at a work load of 80% VO2max, whereas
      only one desaturated at 50% VO2max. This study confirms that with increasing
      severity of disease, maximal exercise capacity may be limited in adult CF
      patients, whereas endurance capacity (at the same relative work load) is
      unimpaired. Furthermore, CF patients who desaturate during a progressive maximal
      exercise test are likely to desaturate during constant work load exercise if the
      intensity is high but unlikely to do so if the intensity is low. The information
      from these exercise tests would be of value for prescribing individual training
      programmes and for evaluating the effects.

PMID- 8265844
TI  - Evaluation of Wright pocket flow meter with mini Wright meter in children and
      adults.

PMID- 8265845
TI  - Plasma cell granuloma.

PMID- 8265846
TI  - A non-invasive technique to measure shunt fraction.

PMID- 8265847
TI  - Lung limited lymphocytic proliferation in human immunodeficiency virus (HIV)
      infection.

PMID- 8265848
TI  - Nebulized bronchodilator therapy causes acute angle closure glaucoma in
      predisposed individuals.

PMID- 8265849
TI  - Bone marrow transplantation for cancer: an overview.

PMID- 8265850
TI  - Effect of colony-stimulating factors on granulocyte function.

PMID- 8265851
TI  - Invasive aspergillosis: host defenses.

PMID- 8265852
TI  - Invasive aspergillosis: serologic diagnosis.

PMID- 8265853
TI  - Aspergillosis in the immunocompromised: focus on treatment.

PMID- 8265854
TI  - Invasive candidiasis during granulocytopenia.
AB  - Candidiasis remains the most frequently encountered fungal infection in patients
      with profound granulocytopenia and appears to be increasing in frequency. In
      addition, Candida infections are occurring earlier during remission induction
      chemotherapy and can be caused by a variety of species such as C. albicans, C.
      tropicalis, and C. krusei. The most frequent source of disseminated infection is
      the gastrointestinal tract, as the integrity of the epithelium is disrupted by
      chemotherapeutic agents. The spectrum of disseminated candidiasis comprises both
      an acute and a chronic presentation (also known in the literature as
      hepatosplenic candidiasis). The management of disseminated infection consists of
      early empiric antifungal therapy with a standard agent, amphotericin B.
      Unfortunately, responses in the setting of profound granulocytopenia appear to be
      poor. Other agents that appear to be useful in the management of disseminated
      candidiasis include 5-flucytosine and fluconazole. Based on animal
      experimentation, it appears that the combination of these three classes of agents
      might produce superior results compared with amphotericin B alone. Removal of the
      central venous catheter does not appear warranted in the setting of profound
      granulocytopenia, and the role of colony stimulating factors needs to be defined.
      Given the severity and high mortality associated with disseminated candidiasis in
      patients with hematologic malignancies, antifungal prophylaxis appears warranted.

PMID- 8265855
TI  - Infections in cancer patients with suppressed cellular immunity.

PMID- 8265856
TI  - Infection in bone marrow transplantation: a model for examining predisposing
      factors to infection in cancer patients.

PMID- 8265857
TI  - Herpes simplex infections.

PMID- 8265858
TI  - Treatment and prophylaxis of cytomegalovirus infection after bone marrow
      transplantation.

PMID- 8265859
TI  - Varicella zoster infections in bone marrow transplants.

PMID- 8265860
TI  - Graft-versus-host disease: basic considerations.

PMID- 8265861
TI  - Graft-versus-host disease: implications.

PMID- 8265862
TI  - Late bacterial infections in humoral immune deficiency.

PMID- 8265863
TI  - Hepatitis B and C: influence of immunosuppression.

PMID- 8265864
TI  - Emergence of gram-positive infections: relationship to indwelling catheters and
      management during chemotherapy-induced aplasia.

PMID- 8265865
TI  - New pathogens in the immunocompromised host.

PMID- 8265866
TI  - Infectious complications in bone marrow transplantation. Resistant bacterial
      infections.

PMID- 8265867
TI  - Organization of clinical trials: problems, controversies, definitions, and
      methodology related to infections in neutropenic patients.

PMID- 8265868
TI  - Infectious complications in bone marrow transplantation. Organization of clinical
      trials: problems, controversies, definitions, methodology.

PMID- 8265869
TI  - Infectious complications in bone marrow transplantation. Introduction to case
      presentation.

PMID- 8265870
TI  - Initial empiric therapy for fever in neutropenia.

PMID- 8265871
TI  - Approach to the patient with prolonged granulocytopenia.
AB  - In most centers treating cancer patients, significant progress has been made in
      permitting patients to survive even prolonged courses of neutropenia. This has
      resulted from a better understanding of the epidemiology of infection and the
      points during the clinical course when they pose a risk for the patient with
      prolonged neutropenia. Considerable benefit has been derived from the
      availability of more potent broad-spectrum antimicrobial agents and from
      organized strategies for when they should be initiated, how and when they should
      be modified, and for how long they should be continued. The possibility that the
      duration of neutropenia might be attenuated in patients receiving chemotherapy
      now seems real with the ever-expanding repertoire of cytokines and other biologic
      agents that augment the hematopoietic and immune systems. Coupled with the use of
      peripheral stem cell reconstitution or the insertion of genes into hematopoietic
      stem cells that might render them resistant to the cytocidal effects of certain
      chemotherapeutic agents, it now seems possible to envision regimens that might
      alter the consequences of neutropenia as we have come to know them. It is likely,
      therefore, as additional experience is garnered and as chemotherapy regimens are
      devised, that the optimal approach to the management of the patient with
      prolonged neutropenia will include the rational use of antibiotics together with
      cytokines and other biologicals. Hopefully, such regimens will permit the
      delivery of chemotherapy in a manner that might enhance its tumoricidal activity
      and improve the outcome of patients with cancer.

PMID- 8265872
TI  - Simplification of empiric therapy for the febrile, neutropenic oncology patient.

PMID- 8265873
TI  - Fever and granulocytopenia: a viewpoint from an academic setting.

PMID- 8265874
TI  - Empiric antimicrobial therapy in the community hospital setting for the cancer
      patient with fever and neutropenia: the need for vigilance and attention to
      detail.

PMID- 8265875
TI  - Normal values for the hypercapnic ventilation response: effects of age and the
      ability to ventilate.
AB  - Normal values reported for the hypercapnic ventilation response (HCVR) vary
      considerably, but the reported normal values have come from studies containing
      small sample sizes and/or the subjects were young or of unidentified age. We
      speculated that age has a major effect on HCVR due to the generally lower maximal
      ventilation (VEmax) of elderly subjects. Therefore, we performed a large study to
      more accurately define the normal range and to reveal any effects which age and
      sex might have on HCVR. We studied 181 normal subjects (69 males, 112 females)
      between the ages of 20 and 93 years. Prior to measuring HCVR we measured forced
      expired volume in 1 s (FEV1) and forced vital capacity to establish whether lung
      function was normal and to obtain an estimate of VEmax. Results for the entire
      group revealed a significant correlation between FEV1 and HCVR [HCVR = 0.51 +
      (0.33 FEV1), r = 0.43, p < 0.001], so it is clear that the ability to ventilate
      can influence HCVR. We also found a significant correlation between age and HCVR
      [HCVR = 2.08-(0.01.age), r = 0.34, p < 0.001]. The mean HCVR for our male group
      (1.86 +/- 0.54 l/min.mm Hg) was significantly higher (p < 0.001) than that for
      the females (1.37 +/- 0.60) even though their mean ages were similar (41.3 vs.
      41.7 years, respectively). We expect that this difference in HCVR was due to the
      higher FEV1 in males compared to females (3.82 vs. 2.83 liter,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265876
TI  - Perception of acute or progressive resistive loads in normal and asthmatic
      subjects.
AB  - To determine if the rapidity of increase in airway resistance influences its
      perception, we looked at the perception of acute and progressive expiratory
      resistive loads in 9 controls (CN) and 9 asthmatics (AS). Each had 4 single-blind
      tests in a randomized order, during which resistances were increased from 0 to 24
      cm H2O/l/s in 1, 3 or 6 steps or decreased in 6 steps. Dyspnea scores were
      recorded on a modified Borg scale (0-10). FEV1 and lung volumes were measured in
      all subjects initially and after the last resistance applied during tests C and
      D. Tidal volume, respiratory rate, the ratio of inspiratory time over total
      breathing time (Ti/Ttot) and minute ventilation were measured throughout each
      test. Borg scores were not significantly different from one test to the other.
      Overall, AS tended to have a higher perception of resistive loads than CN,
      although it did not reach statistical significance. FEV1 did not change
      significantly in both groups between the tests and before and after application
      of resistances. Functional residual capacity was not significantly different
      between AS and CN or before and after the tests. Residual volume was higher in AS
      (mean of the 4 tests: 1.6 +/- 0.05 l) compared to CN (1.1 +/- 0.14 l) (p = 0.003)
      but was unchanged after the applied resistances. Ti/Ttot ratio was similar for AS
      and CN and decreased significantly from 0 to 24 cm H2O/l/s in both groups (all
      tests, p < 0.01). Respiratory rate was higher in CN than in AS at all resistances
      (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8265877
TI  - Theophylline in the inhibition of angiotensin-converting enzyme inhibitor-induced
      cough.
AB  - Preliminary reports suggest that some pharmacologic agents may be effective in
      ameliorating angiotensin-converting enzyme (ACE) inhibitor-induced cough and,
      perhaps, allowing continuing use of ACE inhibitors in patients for whom this
      class of medication is important. We examined the effect of a once-a-day
      theophylline formulation on ACE inhibitor-induced cough and on the sensitivity of
      the cough reflex to capsaicin in 10 hypertensive patients who had developed cough
      during treatment with an ACE inhibitor. Theophylline did not induce
      bronchodilation but induced complete remission of clinical symptoms in 8 and
      attenuated the capsaicin-induced cough number in 7 subjects when compared with
      placebo. Theophylline may thus be effective in preventing ACE inhibitor-induced
      cough.

PMID- 8265878
TI  - Buspirone effect on breathlessness and exercise performance in patients with
      chronic obstructive pulmonary disease.
AB  - Buspirone is an anxiolytic agent that appears to have no sedative effects. The
      aim of this study was to assess the effects of buspirone on breathlessness and
      exercise tolerance in patients with chronic airway obstruction. Sixteen patients,
      age 56.9 +/- 17.0; forced expiratory volume in 1 s (FEV1) 1.15 +/- 0.42 l;
      FEV1/forced vital capacity (FVC) 50.7 +/- 15.0%; PaCO2 42.2 +/- 5.5 mm Hg; and
      PaO2 57.6 +/- 10 mm Hg, underwent a 6-min walking test, an incremental cycle
      ergometer test, an incremental treadmill walking test with self-assessment of
      dyspnea on Borg's scale during exercise and an assessment of respiratory drive (P
      0.1), timing [inspiration time (TI)/total breathing time (Ttot)], PaO2, PaCO2,
      FVC, FEV1, following oral administration for 14 days of placebo or buspirone (20
      mg daily) in a double-blind, cross-over randomized way. We also used the symptom
      check list-90-R for the assessment of subjective complaints and symptomatic
      behavior. A significant improvement in anxiety, depression and obsessive symptoms
      and complaints was noted after buspirone treatment. The P 0.1, TI/Ttot, arterial
      blood gases and respiratory mechanics did not change after drug treatment. There
      was an improvement in exercise tolerance and in the sensation of dyspnea during
      the buspirone period. Thus, as given in this study, oral buspirone has
      therapeutic potential in the treatment of dyspnea in patients with chronic lung
      disease.

PMID- 8265879
TI  - Ultrastructural study of rabbit lung tissue subsequent to capsaicin treatment
      over several days.
AB  - The neurogenic basis of nonspecific airway hyperresponsiveness (NAH) is poorly
      understood. Under experimental conditions isocyanates can elicit bronchial
      hyperresponsiveness in animals. The purpose of our study was to determine whether
      reactions of neurosecretory granules in nonmedullated C fibers might play a role
      in NAH. Our experiments were based on the fact that capsaicin treatment causes
      depletion of neurosecretory granules in vicinity of C fibers. We gave rabbits
      repeated subcutaneous injections of capsaicin. The animals were then treated with
      toluene diisocyanate (TDI), inducing airway hyperresponsiveness upon
      acetylcholine (ACH) inhalation. In capsaicin-treated animals the neurosecretory
      granules were not evident ultrastructurally and airway hyperresponsiveness did
      not occur in response to TDI treatment. Controls that were not treated with
      capsaicin displayed both neurosecretory granules ultrastructurally as well as
      airway hyperresponsiveness to ACH. We conclude that in the rabbit, NAH is related
      to the presence of neurosecretory granules adjacent to nonmedullated C fibers.

PMID- 8265880
TI  - Mycoplasma pneumoniae infection in Hong Kong--clinical and epidemiological
      features during an epidemic.
AB  - An epidemic of infection due to Mycoplasma pneumoniae occurred in Hong Kong in
      1986-1988. One hundred and seventy-nine cases were identified at the Prince of
      Wales Hospital over this period. Clinically significant infection predominantly
      affected children under 12 years, with 32% of all infections occurring in
      children aged between 6 and 11 years, and 39% in children between 1 and 5 years.
      Ninety-seven percent of childhood infections were respiratory in nature, the
      other 4 presentations were neuropsychiatric. Adequate information was available
      on 36 of the 43 subjects over 12 years. One teenager presented with acute
      psychosis; all other cases (35) were respiratory. In these cases cough was
      universal, and fever was present in 34 (97%). A variety of non-specific symptoms
      (rigors/chills, malaise, headache, sore throat, sweating) were frequently noted.
      Sputum production was documented in 75% of cases, and was frequently purulent.
      Radiological consolidation was very common (95% of cases), but resolved fully
      after 4 weeks. Complications were rare and included acute pericarditis in 1
      patient and haemolysis in another, and both patients recovered subsequently.
      Clinical recovery was otherwise rapid and complete in all other patients.
      Persisting dry cough was the only symptom documented at follow-up. Although
      infection due to M. pneumoniae in an ethnic Chinese population appears similar to
      that described in other populations, a higher incidence in younger children was
      recorded in this study.

PMID- 8265881
TI  - Bronchial asthma with Addison's disease.
AB  - A 14-year-old boy with bronchial asthma who was subsequently diagnosed to have
      coexistent Addison's disease is presented. Both diseases responded to continuous
      replacement steroid therapy. We suggest that worsening of bronchial asthma
      symptoms in this patient may be due to the hypocortisolemia produced by the
      coexistent Addison's disease. Patients with Addison's disease with clinical
      evidence of bronchial asthma have rarely been reported [1, 2]. A 14-year-old boy
      in whom symptoms of bronchial asthma obscured the otherwise obvious diagnosis of
      adrenocortical insufficiency is presented.

PMID- 8265882
TI  - Bilateral carotid body paraganglioma and central alveolar hypoventilation.
AB  - A 62-year-old woman with a bilateral carotid body paraganglioma presented, 2
      years after the removal of the right one, with signs of right-heart failure.
      Hypoxemia, hypercapnia, polycythemia and pulmonary hypertension with normal
      ventilatory capacity were found. Central alveolar hypoventilation was diagnosed
      on the basis of absence of ventilatory response and sensation to provoked
      hypercapnia, prolonged breath-holding time and correction of hypercapnia by
      voluntary hyperventilation.

PMID- 8265883
TI  - Coexisting undifferentiated thymic carcinoma and thymic carcinoid tumor.
AB  - Thymic carcinoma is an unusual neoplasm, and the undifferentiated type is rare.
      Thymic carcinoid is also rare. This report describes a patient with coexisting
      undifferentiated thymic carcinoma and a carcinoid tumor. Both lesions were
      completely excised. The carcinoid cells showed argyrophilic granules by
      Grimelius' method and immunoreactivity against neuron-specific enolase, whereas
      the undifferentiated carcinoma cells were negative for argyrophilic stain and
      immunostaining against neuron-specific enolase.

PMID- 8265884
TI  - Scar carcinoma of the trachea after tracheotomy. Case report and review of the
      literature.
AB  - We present another case of squamous cell carcinoma of the trachea developed in a
      tracheotomy scar. In the literature 6 cases of cancer found in tracheotomy scars
      or tracheostomies are reported. The patients' ages ranged from 6 to 66 years. The
      interval between tracheotomy and the occurrence of cancer ranged from 3 to 41
      years. Local extirpation and radiotherapy were tried. The use of stents is
      emphasized.

PMID- 8265885
TI  - Acyclovir in varicella pneumonia in healthy adults.

PMID- 8265886
TI  - Mediastinal fibrosis and radiofrequency radiation.

PMID- 8265887
TI  - Different characteristics of neuroblastomas in cases found by mass screening and
      non-screening: evaluation of mass screening for neuroblastoma in Kitakyushu City.
AB  - Neuroblastoma accounts for 24 of 109 patients who have been managed by the
      pediatric tumor outpatient clinic of our university hospital. Among the malignant
      solid tumors, neuroblastomas are the most numerous. We investigated
      neuroblastomas found by mass screening oncologically and epidemiologically. Up
      until March 31, 1991, seven cases were detected from 64,885 infants who received
      mass screening by the Kitakyushu City System which we had introduced in 1985.
      This system is based on an individual health survey program for infants in the
      city. Six of seven cases found by the screening were treated in our department.
      None of them, including stage III and stage IV cases, showed any conventional
      risk factors such as high serum levels of neuron specific enolase, ferritin,
      amplification of N-myc gene, nor cytogenetic abnormalities. Histopathological
      studies revealed that ganglioneuroblastoma was observed in 9 of 13 cases over one
      year of age, whereas it was observed only in two screened cases out of 11 cases
      under one year of age. According to the classification of Shimada et al., there
      was one stroma-rich tumor, which is rare in infants and usually a matured type,
      in the screened cases. Interestingly, another one of the six screened cases
      regressed spontaneously without any treatment. These cases suggested that some
      neuroblastomas in the process of maturation or spontaneous regression could be
      detected by mass screening. On the other hand, 9 of 13 non-screened cases over
      one-year-old died. Although mass screening at six months of age decreased the
      mortality rate by neuroblastoma in infancy, the prognosis of neuroblastoma in
      patients over one-year-old remained still poor. Mass screening should be carried
      out in a health survey program at one year and six months of age in order to
      improve the outcome.

PMID- 8265888
TI  - Histologic evaluation of tumor persistence at the surgical margins in oral
      cancer: an evaluation of all surgical margins using paraffin-embedded sections
      and its usefulness and limitations.
AB  - An evaluation of frozen sections at all surgical margins (Mohs' surgery) was
      attempted in three patients, in order to determine whether or not a tumor
      persisted at the surgical margins following surgery for carcinoma of the oral
      cavity. However, sectioning from the fresh tissue was difficult, and moreover,
      duration of the surgery was lengthened. It thus seems that this method is not
      suitable for a routine evaluation of the surgical margins. Based on this,
      surgical specimens after formalin fixation were evaluated in eight patients. The
      use of paraffin-embedded sections compensates the disadvantages in using frozen
      sections. On the other hand, when a residual tumor is detected, any additional
      excision should be delayed. In two patients, who were evaluated using paraffin
      embedded sections, a persistent tumor was detected. In another patient a
      recurrent tumor developed, despite having completely tumor-free margins. In this
      patient, the growth of the tumor appeared to be discontinuous. When skip lesions
      are histologically suggested, adjuvant therapy including radiotherapy should be
      considered, even when a persistent tumor is not evident. A reliable evaluation of
      all surgical margins is difficult in either a T4 tumor or in a malignant tumor of
      the gingiva and hard palate. Microscopic evaluation of all surgical margins using
      paraffin-embedded sections is considered to be practical in helping to elucidate
      the microscopic extent of a tumor, although there are several limitations in its
      application.

PMID- 8265889
TI  - Determination of blood and urine manganese (Mn) concentrations and the
      application of static sensography as the indices of Mn-exposure among Mn-refinery
      workers.
AB  - Early detection of neurophysiological abnormalities is believed to be most
      effective for the early diagnosis of chronic manganism. The static sensography
      was applied during the periodical health examination and the significance of
      total distance of the postural sway (i. e. postural sway index) as a
      neurophysiological index was studied in relation to the blood and urine manganese
      concentrations. Sixty-six workers in a manganese (Mn)-refining factory, aged 29
      59 (mean 47) years, were examined from 1984 to 1989. Mn-exposed workers had been
      engaged in alternating shifts and the mean duration of Mn exposure was 22.6 years
      before the health examination in 1984. Air-borne dust and Mn levels in the
      working environment were 0.07-2.74 mg/m3 and 0.02-0.46 mg/m3. The mean values of
      the parameters in Mn-exposed workers fluctuated as follows: blood Mn
      concentrations 19.1-26.9 micrograms/l [control; Mean 17.8 (Standard deviation
      5.2) micrograms/l], urine Mn concentration 2.60-4.22 micrograms/g Creatinine
      [control; Geometric mean 1.16 (Geometric standard deviation 1.93) micrograms/g
      Creat.] and postural sway index 51.4-94.6 cm/30 sec [control; Geometric mean 59.7
      (Geometric standard deviation 1.4) cm/30 sec.]. Although there were no
      significant correlations between the postural sway index and blood and urine
      manganese concentrations, the usefulness of this kind of simple
      neurophysiological test should be further investigated in combination with other
      established examinations.

PMID- 8265891
TI  - [Psychopathology of waking after anesthesia].

PMID- 8265890
TI  - [A case of acute polyradiculoneuropathy with autonomic disturbances following
      rubella infection].
AB  - A 32-year-old man developed a rash on his body and extremities following acute
      fever of a few days duration, and also noticed pain and spontaneous tingling
      sensations in his lower extremities. Because severe pneumonia with dyspnea and
      low arterial blood oxygen concentration were found on examination, he was
      admitted and treated. After recovering from pneumonia in two months, he
      complained of abdominal symptoms, such as constipation, nausea and vomiting,
      spontaneous tingling sensations in the lower extremities, and orthostatic
      dizziness and fainting. On neurological examination, a mild to moderate muscle
      weakness was found in the distal muscles of both extremities. The ankle jerk was
      absent. Both superficial and deep sensations were moderately to severely
      decreased in the feet with positive Romberg's sign. Constipation and vomiting
      with nausea were noted. Clinical and laboratory examinations revealed marked
      orthostatic hypotension and hypohidrosis. Motor and sensory conduction studies
      indicated the presence of axonal degeneration and segmental demyelination and
      remyelination in the limbs nerves. CSF examination indicated that protein was 150
      mg/dl and the cell count to be 18/mm3. Titer of antibody to rubella virus was
      significantly elevated. There were no other abnormalities to indicate the cause
      of motor, sensory and autonomic neuropathies. Therefore, the diagnosis of acute
      polyradiculoneuropathy with autonomic disturbances after rubella infection, which
      is rare in the literature, was made.

PMID- 8265892
TI  - [An open recovery room during the day].

PMID- 8265893
TI  - [A recovery room, open 24 hours out of 24].

PMID- 8265894
TI  - [The role of the nurse in the recovery room].

PMID- 8265895
TI  - [Recommendations about postanesthetic surveillance and care].

PMID- 8265896
TI  - [The nurse anesthetist in the recovery room].

PMID- 8265897
TI  - [Transmissions in the recovery room].

PMID- 8265898
TI  - [Pediatric recovery room].

PMID- 8265899
TI  - [Crural hernias: definition and treatment].

PMID- 8265900
TI  - [Recovery rooms in France: rules, current situation and perspectives].

PMID- 8265901
TI  - [A little bit of history].

PMID- 8265902
TI  - [Surgical technique].

PMID- 8265903
TI  - [Role and place of the operating room nurse during an aortocoronary bypass].

PMID- 8265904
TI  - [Anesthesia in coronary artery surgery].

PMID- 8265905
TI  - [Surgical anatomy of the coronary arteries].

PMID- 8265906
TI  - [Role and place of the nurse anesthetist during aortocoronary bypass].

PMID- 8265907
TI  - [Development in intensive care after aortocoronary bypass].

PMID- 8265908
TI  - [Preoperative and postoperative nursing care in elective surgery].

PMID- 8265909
TI  - [Indications for surgery].

PMID- 8265910
TI  - [Chronic renal failure].

PMID- 8265911
TI  - [The immune system and immunosuppression].

PMID- 8265912
TI  - [The patient awaiting a renal transplant].

PMID- 8265913
TI  - [The condition before transplantation].

PMID- 8265914
TI  - [Coordination of organ procurement].

PMID- 8265915
TI  - [Making them smile again].

PMID- 8265916
TI  - [Admission of the patient at the surgical suite].

PMID- 8265917
TI  - [Nursing surveillance of the immunosuppressive treatment].

PMID- 8265918
TI  - [Immediate postoperative monitoring].

PMID- 8265919
TI  - [Kidney transplantation].

PMID- 8265920
TI  - [Monitoring of complications during the first year].

PMID- 8265921
TI  - [Rejection of the graft].

PMID- 8265922
TI  - [Vascular and urologic complications].

PMID- 8265924
TI  - [Anatomy of the kidneys].

PMID- 8265923
TI  - [Consultations after transplantation. The place of the nurse].

PMID- 8265925
TI  - [Biopsy puncture of the kidney graft].

PMID- 8265926
TI  - [Hopes for the future].

PMID- 8265928
TI  - [Tracheotomy (2)].

PMID- 8265927
TI  - [Organization of a surgical day hospital for adults and children].

PMID- 8265929
TI  - [Elements of nursing care within the framework of home hospice care for patients
      with HIV infections].

PMID- 8265930
TI  - [The thyroid gland. Surgery of a thyroid nodule].

PMID- 8265931
TI  - [Physiology of the kidney].

PMID- 8265932
TI  - [Peroperative care].

PMID- 8265933
TI  - [Treatment of fractures of the femoral diaphysis in children].

PMID- 8265934
TI  - [How to act, in the emergency service, in front of a patient with altered
      consciousness].

PMID- 8265935
TI  - [The patient with an otorhinolaryngologic neoplasm and his nursing care].

PMID- 8265937
TI  - [Hemodialysis].

PMID- 8265938
TI  - [What is your diagnosis? Glioblastoma multiforme (grade IV astrocytoma) verified
      with a histological biopsy].

PMID- 8265936
TI  - [Thyroid cancer].

PMID- 8265939
TI  - [Heart pacemaker therapy: a guideline for clinical practice].
AB  - Pacemakers have evolved enormously over the past 15 years because of technical
      developments in the field of microprocessors. Implantation of physiologic dual
      chamber systems (DDD pacemakers) have gained growing importance. The goal of
      therapy with modern pacemakers is to relieve symptoms under rest as well as under
      hemodynamic load. Next to indications for and explications on the function of the
      various systems (single and dual chamber systems, rate responsive pacemakers)
      this article covers hemodynamic consequences of pacemaker implantation.
      Particular reference is made to the follow-up of patients with pacemakers and to
      the possibility of external interference with these devices. A glossary of
      pacemaker therapy is given in the appendix.

PMID- 8265940
TI  - [Anatomo-clinical conference of the internal medicine department. Hepatomegaly
      with ascites of recent onset].

PMID- 8265941
TI  - [Muscle weakness].
AB  - A 61 year old man complained initially about pain in the left lower leg with
      increasing swelling of the entire left leg. A slight swelling of the left ankle
      and knee and an erythematous skin change of 5 cm diameter developed and
      disappeared after a few hours. Two days later the patient complained about a
      sudden and massive weakness of the proximal skeletal muscles, progressive
      disturbance of swallowing, hoarseness and dark red to bluish erythematous skin
      eruptions on the right knee and buttock. An elevated creatinine-kinase and
      lactate-dehydrogenase were found. Dermatomyositis was diagnosed and treatment
      with high dose steroids initiated. Under this treatment the patients condition
      deteriorated dramatically. A treatment with plasmapheresis and cyclophosphamide
      was begun. A significant improvement occurred over three weeks. The patient was
      discharged, rehabilitated and remains free of symptoms on 10 mg cortisone. A
      neoplasm has so far not been detected.

PMID- 8265942
TI  - [A case from practice (281). Sjogren syndrome. Monoclonal gammopathy, IgA-Type
      K].

PMID- 8265943
TI  - [What is your diagnosis?].

PMID- 8265944
TI  - [Clinical pharmacy--a novel interdisciplinary cooperation of pharmacist and
      physician].

PMID- 8265945
TI  - [Patient-oriented pharmacy: an obligation for the hospital pharmacist in
      Switzerland?].
AB  - The developments in the profession of a pharmacist from traditional product- to
      patient-oriented activities are briefly reviewed. The latter aim at the
      amelioration of therapy as a consequence of increased security of treatment from
      drug prescription to its administration. These developments, originally arisen in
      the USA, now have gained a foothold in Europe, influencing in particular the work
      of hospital pharmacists here. The proposed European program for specialisation
      (EAHP, post-graduate education) fulfills the prerequisites and serves the Swiss
      hospital pharmacists as basis for the institution of a specific education.
      Concrete pilot-projects exist, however there is still a marked lack of funded
      positions for education in this field.

PMID- 8265946
TI  - [Clinical education of pharmacists: the Sion Model].
AB  - A post-graduate training program in clinical pharmacy for pharmacists is
      described. The yearly program gives an overview of the various activities. A
      detailed description of one working day delivers insight into the activities of a
      clinical pharmacist in a department of internal medicine. Clinical education of a
      pharmacist should enable him to apply his knowledge in the context of a practical
      cooperation with physicians and nursing staff and to consider patient,
      counselling and medication as a unit.

PMID- 8265947
TI  - [The drug information service in the hospital].
AB  - A Drug Information Service (MID) delivers competent information, free from
      influences of industry. Users are mainly physicians and pharmacists, who are not
      able to solve a particular pharmacologic problem by their own means. For many
      years such MIDs are operated in several countries by clinical pharmacists. In
      Switzerland, too, there is particular interest in drug-oriented information for
      years. In this article a short overview on basic informations and first
      experiences concerning this domain are presented.

PMID- 8265948
TI  - [Drug safety in the hospital].
AB  - Worldwide attention to problems with drug-related malpractice in hospitals has
      gained growing interest. Several studies have been carried out aiming at the
      identification of sources for errors and the reduction of the error rate. The
      presented study was performed on to answer the question, whether and how
      effectively drug-related activities in hospitals can be influenced by competent
      pharmaceutic knowledge, in order to enhance security during therapy and to
      promote rational and economic pharmacotherapy and interdisciplinary collaboration
      between physician, nursing staff and pharmacist.

PMID- 8265949
TI  - [Drug incompatibilities. Problems in the simultaneous administration of drugs in
      infusions].
AB  - It is common practice in hospitals to administer drugs by infusion; thereby
      combinations of various drugs are frequent with respect to the patient's comfort
      and in order to save time. Various possibilities of combinations are presented
      and risks deriving from this form of application are discussed. In particular the
      risk for incompatibilities is emphasized and measures for prevention are
      recommended.

PMID- 8265950
TI  - Teaching and learning activities in Project 2000.

PMID- 8265951
TI  - The nurse's counselling role in health promotion.

PMID- 8265952
TI  - HIV mistreatment: policy, resources and practice.

PMID- 8265953
TI  - Preparing undergraduate nurses to care for dying patients.

PMID- 8265954
TI  - Under evaluation.

PMID- 8265955
TI  - Strategic change in the NHS.

PMID- 8265956
TI  - Death and dying, oh no!

PMID- 8265957
TI  - Insider ethnographies.

PMID- 8265959
TI  - Research-based approach to nursing care.

PMID- 8265958
TI  - A quality professional service.

PMID- 8265960
TI  - A profile of part-time students.

PMID- 8265961
TI  - Taking forward your human resource agenda.

PMID- 8265962
TI  - Preparing the way for Project 2000 students.

PMID- 8265963
TI  - Vasodilator and vasoconstrictor substances produced by the endothelium.

PMID- 8265964
TI  - Barnacle muscle: Ca2+, activation and mechanics.
AB  - In this review, aspects of the ways in which Ca2+ is transported and regulated
      within muscle cells have been considered, with particular reference to crustacean
      muscle fibres. The large size of these fibres permits easy access to the internal
      environment of the cell, allowing it to be altered by microinjection or
      microperfusion. At rest, Ca2+ is not in equilibrium across the cell membrane, it
      enters the cell down a steep electrochemical gradient. The free [Ca2+] at rest is
      maintained at a value close to 200 nM by a combination of internal buffering
      systems, mainly the SR, mitochondria, and the fixed and diffusible Ca(2+)-binding
      proteins, as well as by an energy-dependent extrusion system operating across the
      external cell membrane. This system relies upon the inward movement of Na+ down
      its own electrochemical gradient to provide the energy for the extrusion of Ca2+
      ions. As a result of electrical excitation, voltage-sensitive channels for Ca2+
      are activated and permit Ca2+ to enter the cell more rapidly than at rest. It has
      been possible to determine both the amount of Ca2+ entering by this step, and
      what part this externally derived Ca2+ plays in the development of force as well
      as in the free Ca2+ change. The latter can be determined directly by Ca(2+)
      sensitive indicators introduced into the cell sarcoplasm. A combination of
      techniques, allowing both the total and free Ca2+ changes to be assessed during
      electrical excitation, has provided valuable information as to how muscle cells
      buffer their Ca2+ in order to regulate the extent of the change in the free Ca2+
      concentration. The data indicate that the entering Ca2+ can only make a small
      direct contribution to the force developed by the cell. The implication here is
      that the major source of Ca2+ for contraction must be derived from the internal
      Ca2+ storage sites within the SR system, a view reinforced by caged Ca2+ methods.
      The ability to measure the free Ca2+ concentration changes within a single cell
      during activation has also provided the opportunity to analyse, in detail, the
      likely relations between free Ca2+ and the process of force development in
      muscle. The fact that the free Ca2+ change precedes the development of force
      implies that there are delays in the mechanism, either at the site of Ca2+
      attachment on the myofibril, or at some later stage in the process of force
      development that were not previously anticipated.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8265965
TI  - Muscle relaxation and sarcoplasmic reticulum function in different muscle types.

PMID- 8265966
TI  - [Integral care for the ostomy patient. Program evaluation].

PMID- 8265967
TI  - [Child accidents in the home].

PMID- 8265968
TI  - [The exigencies of the current health reform. Promoting the self-esteem of health
      professionals].

PMID- 8265969
TI  - [Evaluating the quality of nurse registries. A pilot study of 2 primary care
      centers].

PMID- 8265970
TI  - [We intend to assure the quality of nursing care. The birth of the Alumni
      Association of the School of Nursing of the University of Barcelona].

PMID- 8265971
TI  - [The nurses' aide in the project of Health for All in the Year 2000].

PMID- 8265972
TI  - [The constitutional ordinances of the Gran Hospital Real de Santiago].

PMID- 8265973
TI  - [The air mattress. Preventing decubitus ulcers].

PMID- 8265975
TI  - [The principle of the opening to specialties?].

PMID- 8265974
TI  - [Psychiatric patients. Their socio-demographic and nursing profiles].

PMID- 8265976
TI  - [The incubator].

PMID- 8265977
TI  - [Continuing education. 84. The general concepts of the psychosocial sciences].

PMID- 8265978
TI  - Variability of tumor markers in the follow-up of patients radically resected for
      breast cancer.
AB  - The biological and analytical components of variability of tumor markers should
      be distinguished from the variations due to tumor progression. The aim of the
      present study was to evaluate tumor marker variability in the follow-up of
      patients resected for breast cancer. So far, we have carried out 2,085 CEA and
      2,550 CA 15-3 determinations in 435 patients. The total variability of both CEA
      and CA 15-3 was widely scattered among different subjects (CEA coefficient of
      variation 0-105%; CA 15-3 coefficient of variation 0-89.2%). The biological
      variability of CA 15-3, which was calculated in a limited number of cases, was
      scattered between 0 and 23% and was higher than the intra-assay variability. From
      these findings we conclude that when evaluating serial marker assays the intra
      individual variability should be assayed initially to obtain a reference value of
      individual variability in relapse-free conditions.

PMID- 8265979
TI  - Bisected N-acetylglucosamine residue of biantennary sugar chains and high
      molecular-weight oligosaccharides of neuroblastoma cell membranes.
AB  - The carbohydrate moieties of glycoproteins in plasma membrane are known to
      correlate with the induction of cell differentiation in some kinds of cells. We
      investigated the asparagine-linked sugar chains of neuroblastoma and
      ganglioneuroma cell membranes. The acidic oligosaccharides were bi-, tri-, and
      tetraantennary complex-type sugar chains with Man alpha-->(Man alpha)Man beta-
      >GlcNAc beta-->(+/- Fuc alpha-->)GlcNAc as their cores. A comparative study of
      the oligosaccharides of these cells showed that the biantennary complex-type
      sugar chain with bisecting N-acetylglucosamine residues increased and high
      molecular-weight oligosaccharides decreased in ganglioneuroma cells. It is
      suspected that asparagine-linked sugar chains correlate with the differentiation
      stage of neuroblastoma.

PMID- 8265980
TI  - Emergence of self-organization in tumor cells: relevance for diagnosis and
      therapy.
AB  - The cell is a complex system functioning outside a thermodynamic equilibrium. The
      prediction of cellular functions based exclusively on molecular evidence is still
      impossible because of the large number of interacting molecules and the nonlinear
      interactions between cellular subsystems. The system cell displays a surprisingly
      small spectrum of macroscopically observable degrees of freedom. Their number and
      characteristics, however, are different in normal and neoplastic growth. As
      illustrated by image analytical, microanalytical and other cell biological data
      we demonstrate that certain cellular observables--termed order parameters--may
      serve as indicators for normal and neoplastic growth. The data indicate that the
      transition between normal and neoplastic growth can be understood as a phase
      transition of the mitogenic signalling network. In this interpretation, the order
      parameters of normal and neoplastic cells are the result of cellular self
      organization.

PMID- 8265981
TI  - Expansion of peripheral blood natural killer cells correlates with clinical
      outcome in cancer patients receiving recombinant subcutaneous interleukin-2 and
      interferon-alpha-2.
AB  - Natural killer (NK) cells are believed to contribute to the clinical efficacy of
      cancer immunotherapy using recombinant interleukin-2 (rIL-2) in humans. In
      previous trials of high-dose i.v. rIL-2, however, no correlation has been
      established between circulating NK cells and treatment response. Between January
      1989 and October 1990, we treated a total of 47 outpatients with advanced tumors
      using low-dose s.c. rIL-2 and interferon-alpha-2 (rIFN-alpha). Therapy consisted
      of a 2-day rIL-2 pulse at 18 million IU/m2/day, followed by 6 weeks of rIL-2 (3.6
      x 10(6)-4.8 x 10(6) IU/m2/day x 5 days/week) and rIFN-alpha (5 x 10(6)-6 x 10(6)
      U/m2 x 3/week). Before and after therapy, we phenotypically evaluated circulating
      lymphocytes and correlated them with clinical response. During 6-week therapy,
      peripheral blood lymphocytes bearing the CD56 (NK-cell-associated) surface
      antigen were increased significantly (p < or = 0.005) in treatment responders
      [complete response (CR) and partial response (PR), n = 10; 3.8-fold] and stable
      disease (SD) patients (n = 20; 2.1-fold), while patients with progressive disease
      (PD, n = 17) exhibited no significant expansion of circulating NK cells (p >
      0.1). After one 6-week treatment cycle, CR/PR patients had significantly more
      peripheral NK cells, when compared with patients in SD (1.6-fold) and PD (1.9
      fold) (p < 0.04). The overall number of circulating lymphocytes was also
      increased upon therapy (1.6-fold; p < or = 0.001), but remained independent of
      response (p > 0.4). These data demonstrate that s.c. rIL-2 and s.c. rIFN-alpha
      produce a significant increase in peripheral blood NK cells; this expansion
      correlates significantly with treatment response in advanced tumor patients
      receiving long-term combination immunotherapy at outpatient doses.

PMID- 8265982
TI  - Galaptin and galaptin-binding glycoconjugates in serum and effusions of carcinoma
      patients.
AB  - The objectives of this study were (1) to quantify galaptin, an endogenous lectin,
      and galaptin-binding glycoconjugates present in normal serum, (2) to determine if
      these components were altered in the serum and effusions of carcinoma patients
      with advanced disease, and (3) to determine if ovarian carcinoma cells synthesize
      and release soluble galaptin inhibitors. Serum from healthy females (n = 10) had
      a mean galaptin content of 96 +/- 40 ng/ml. Galaptin levels in carcinoma patient
      serum (n = 29) were depressed (mean 21 +/- 23 ng/ml; p < 0.0001). Galaptin was
      not detected in 6 of 8 ovarian carcinoma patient sera. Effusions (n = 17) had a
      mean galaptin content of 358 +/- 326 ng/ml. Assays involving inhibition of
      binding of galaptin-peroxidase conjugates to asialofetuin were carried out to
      evaluate the levels of galaptin-binding glycoconjugates in serum and effusions.
      The mean inhibition titer of normal serum (n = 12) was 75 +/- 38. Patient serum
      (n = 28) had an elevated inhibitor content (mean titer = 304 +/- 155; p <
      0.0001). Effusions (n = 17) also had a higher inhibitor content relative to
      normal serum (mean titer = 247 +/- 202; p = 0.0037). Ovarian carcinoma cells
      isolated from effusions and cultured in vitro were shown to synthesize and
      release into the medium galaptin-binding glycoconjugates of molecular mass 100
      200 kD. An ovarian carcinoma cell line, A121, released galaptin-binding
      glycoconjugates of molecular mass > or = 200 kD into the medium. The data
      presented show that the levels of soluble galaptin and galaptin-binding
      glycoconjugates in the serum of advanced cancer patients are perturbed relative
      to normal female serum.

PMID- 8265983
TI  - More information on preventing Lyme disease.

PMID- 8265984
TI  - More information on preventing Lyme disease.

PMID- 8265985
TI  - Self-scheduling turned us into a winning team.

PMID- 8265986
TI  - Defusing the violent patient.

PMID- 8265988
TI  - One step closer to safe transfusions.

PMID- 8265987
TI  - Managing transfusion reactions.

PMID- 8265989
TI  - 1993 earnings survey. How your fringe benefits stack up.

PMID- 8265990
TI  - FDA approved new drug bulletin.

PMID- 8265991
TI  - New pins in the RN collection.

PMID- 8265992
TI  - Hypertension new guidelines, new roles.

PMID- 8265993
TI  - Reporting to the FDA.

PMID- 8265994
TI  - Is there a link between smoking and HIV?

PMID- 8265995
TI  - Losing your mind.

PMID- 8265996
TI  - Ensuring adequate pain relief for seriously ill patients.

PMID- 8265997
TI  - Rx for the holidays: simple gifts, memorable moments.

PMID- 8265998
TI  - Turnover and distribution of cathepsin G in the rat.
AB  - The turnover of 125I labelled rat polymorphonuclear leukocyte (PMN) cathepsin G
      with retained enzymatic activity was followed 180 min after an intravenous
      injection. The plasma half-life of injected radioactivity was approximately 4.5
      min. In the plasma sample 15 min after injection the main part of the
      radioactivity in a gel filtration eluted at the same volume as 3-iodo-tyrosine (3
      IT). After 15 min the liver contained about one third of the injected
      radioactivity. Radioactivity in all organs declined in the course of time. In the
      pancreas autoradiography showed labelling at the localization of enzyme granules
      as soon as 15 min after the intravenous injection of radiolabelled substance. All
      these results suggest a rapid uptake and degradation of cathepsin G in the liver.
      The distribution of cathepsin G in tissues analysed in the normal rat were
      localized to the spleen, lymph nodes, and lung. PMNs were immunohistochemically
      stained, while in the lung indefinable epithelial cells were stained. When rat
      PMN cathepsin G was added to normal rat plasma, we could identify 36% bound to
      alpha 1-macroglobulin (alpha 1M) and 19% bound to alpha 1-inhibitor 3 (alpha 1I3)
      as judged from analysis of gel filtration chromatography and electroimmunoassay
      (EIA) with autoradiography.

PMID- 8265999
TI  - Disposal of atrial natriuretic factor (ANF99-126) in patients with cirrhosis:
      effect of beta-adrenergic blockade.
AB  - To test a possible effect of blood flow change on disposal of atrial natriuretic
      factor: ANF99-126 (ANF), we determined renal, azygos, hepatic and cubital venous,
      and arterial plasma concentrations of ANF in 18 patients with cirrhosis before
      and after ingestion of propranolol 80 mg. Arterial ANF was similar to that of
      controls (9.4 vs. 10.9 pmol l-1, NS) and was positively correlated to cardiac
      output (r = 0.49, p < 0.02) and to right atrial pressure (r = 0.44, p < 0.01).
      All the vascular beds examined extracted ANF significantly. The renal (n = 17),
      hepato-enteric (n = 16), and splanchnic superior collateral (azygos) beds (n =
      13) had significantly higher extraction ratios (0.34-0.39) than that observed in
      the cubital vein (0.24, n = 15, p < 0.05). Arterial ANF showed no significant
      change (9.6-11.0 pmol l-1, NS) after reduction of cardiac output (-25%, p <
      0.001) by propranolol. Only insignificant changes in ANF extraction and a small
      decrease in azygos and hepato-enteric clearance occurred during beta-adrenergic
      blockade. Our results show a substantial extraction of ANF in the kidney, in the
      splanchnic bed drained through superior portosystemic collaterals, and in the
      hepato-enteric bed. Only minor effects on ANF extraction were observed after
      reduction of the blood flow with propranolol.

PMID- 8266000
TI  - Effects of psychological stress on plasma interleukins-1 beta and 6, C-reactive
      protein, tumour necrosis factor alpha, anti-diuretic hormone and serum cortisol.
AB  - The study was undertaken to determine whether psychological stress influences
      immunobiological functions and is an important preanalytical factor to be
      considered in connection with blood specimen collection. Two kinds of stress were
      applied, the Stroop colour conflict test and the thrill of a novice about to make
      the first jump with a parachute. In both test situations, the level of the stress
      indicators cortisol or anti-diuretic hormone rose significantly. The
      concentrations of the cytokines studied did not change significantly. However, in
      the parachute test significant positive correlations were found, e.g. between the
      changes of cortisol and C-reactive protein and between anti-diuretic hormone and
      interleukin-1 beta. This suggests that there is an interaction between the
      endocrine and the immune systems in the response to a psychological stress.

PMID- 8266001
TI  - Evaluation of a new chromogenic substrate assay for the measurement of the
      prothrombin time.
AB  - The chromogenic prothrombin time assay Nycotest Chrom was evaluated and compared
      with another chromogenic assay (Chromoquick) and with the well-known
      coagulometric Thrombotest. The intra-assay variation of the test was satisfying
      both in the normal range (CV = 3.6%) and in the therapeutical range of oral
      anticoagulation (CV = 3.5%). These values were somewhat higher than those of the
      Chromoquick test (1.3% and 1.1%) and those of the Thrombotest (2.3% and 2.5%).
      The inter-assay variation coefficient amounted to 3.3% in the normal range and in
      the therapeutical oral anticoagulation range to 4.4%. The respective values for
      the Chromoquick test were somewhat lower (2.2% and 3.9%), those of the
      Thrombotest in the normal range were also lower (2.1%), and in the therapeutical
      range they were much higher (9.2%). The coefficients of correlation of the
      Nycotest Chrom test in the therapeutical range were highest when comparing them
      with those for the Chromoquick test (r = 0.97; p < 0.0001) and somewhat lower in
      comparison with the Thrombotest (r = 0.95; p < 0.0001). The results of the three
      methods paralleled also in the starting phase of oral anticoagulation treatment.
      Storage at 4 degrees C and at 25 degrees C showed good stability of the Nycotest
      Chrom reagent for up to 24h. We conclude that the Nycotest Chrom assay is well
      suited for the measurement with a centrifugal fast analyser, which is attractive
      on behalf of the usually large series of request for prothrombin time
      measurements when monitoring oral anticoagulation therapy.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8266002
TI  - Plasma immunoreactive neuropeptide Y in congestive heart failure at rest and
      during exercise.
AB  - The purpose of the study described here was to study plasma immunoreactive
      Neuropeptide Y (NPY) at rest and during exercise in patients with congestive
      heart failure (CHF) and in healthy subjects. Thirty-five patients, mean age 64
      years, with CHF in optimal treatment and with a mean ejection fraction of 32%,
      were studied at rest and during exercise. Twelve age and sex matched healthy
      subjects were compared for resting values. Another nine healthy subjects were
      studied at rest and during exercise at a constant low load of 75W and at a high
      load defined as 80% of their individual maximal capacity. In patients with
      congestive heart failure mean plasma immunoreactive NPY at rest was 10.3 pmol l-1
      and was not significantly different from the control group. No differences
      between patients with slight and severe CHF were found and there was no
      correlation between plasma immunoreactive NPY and left ventricular ejection
      fraction. Mean maximal exercise time was on average 6.3 min. Only three patients
      exercised more than 10 min. At maximal exercise mean plasma immunoreactive NPY
      was 10.6 pmol l-1 the same as at rest. Plasma noradrenaline was increased in CHF
      patients compared to healthy subjects, and rose further during exercise. In
      healthy subjects plasma immunoreactive NPY rose significantly on both workloads,
      but more on the high load (p < 0.05), when the rise was first significant after
      10 min. Plasma immunoreactive NPY at rest and during exercise was not increased
      in CHF patients in optimal medical treatment. Consequently plasma immunoreactive
      NPY is not a useful marker of the severity of CHF in these patients.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266003
TI  - Diurnal blood pressure profile in patients with severe congestive heart failure:
      dippers and non-dippers.
AB  - Patients with severe congestive heart failure (CHF) have increased sympathetic
      nervous activity and altered baroreceptor function, which may influence the
      diurnal blood pressure rhythm. The 24-h blood pressure profile was measured in 25
      patients with severe CHF (mean ejection fraction: 17%) and 25 control subjects.
      Systemic blood pressure was measured automatically at the arm by a non-invasive
      blood pressure monitoring system every 15 min. The mean +/- SD systolic blood
      pressure in CHF patients and controls was during day-time 105 +/- 10 and 130 +/-
      11 mm Hg and night-time 97 +/- 10 and 112 +/- 10 mm Hg, i.e. the nocturnal
      decrease was 9 +/- 6 and 18 +/- 8 mm Hg, respectively (p < 0.0005 for all). The
      subjects could be divided into two groups: dippers and non-dippers, with and
      without a relative decrease in nocturnal systolic blood pressure > 10%. There was
      significantly more non-dipping CHF patients (16) than controls (5) (p < 0.01).
      Systolic blood pressure was in CHF dippers vs. non-dippers during day-time: 108
      +/- 7 vs. 104 +/- 12 mm Hg (NS) and night-time: 92 +/- 7 vs. 99 +/- 11 mm Hg (p =
      0.08). The nocturnal decrease was 16 +/- 3 vs. 5 +/- 4 mm Hg and the relative
      nocturnal decrease 15 +/- 3 vs. 5 +/- 3% (p < 0.00001 for both). It is concluded
      that patients with severe congestive heart failure can be divided into two
      groups: dippers and non-dippers, with and without a normal decrease in nocturnal
      blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266004
TI  - Effect of cold pressor test and awareness of hypertension on platelet function in
      normotensive and hypertensive women.
AB  - Plasma beta-thromboglobulin (beta-TG) concentration, reflecting platelet function
      in vivo, was compared in fertile women with untreated essential hypertension and
      age-matched normotensives, in two separate studies. In the first study,
      hypertensives and normotensives were aware of their blood pressure status. Blood
      was sampled through arterial and venous indwelling catheters, and no difference
      in beta-TG was found between the groups. Arterial beta-TG was significantly lower
      than venous concentration (p < or = 0.05). Cold pressor test increased arterial
      beta-TG significantly in both groups (p < 0.05). In the second study, both women
      and investigator were unaware of blood pressure status, and beta-TG
      concentration, platelet count, and mean platelet volume obtained by venipunctures
      were similar in the hypertensive and normotensive group. Thus, platelet function
      in vivo seems to be normal in fertile hypertensive women, in contrast to the
      platelet dysfunction previously reported in hypertensive men. In women, as in
      men, platelet release occurred during venous catheter blood sampling and during
      cold pressor test. However, at variance from men, platelet function was not
      influenced by awareness of blood pressure status in the hypertensive females.

PMID- 8266005
TI  - Water immersion and salt-sensitivity in essential hypertension.
AB  - It has been demonstrated that an exaggerated natriuretic response to central
      hypervolaemia is not necessarily associated with hypertension; many hypertensive
      subjects manifest either an appropriate or a blunted natriuresis in response to
      ECFV expansion attained by head-out water immersion. In this study, we tested the
      hypothesis that an underlying condition of salt-sensitivity may explain the
      heterogeneity of the natriuretic response of essential hypertension. Both salt
      sensitivity tests and 2h water-immersion studies were randomly performed in 18
      untreated essential hypertensives under a selected and controlled diet. Salt
      sensitivity was defined as a significant drop in mean arterial pressure of 10% or
      greater, calculated as the difference between the average of the 25 readings
      under the high and the low salt period. Water immersion did result in a
      significant natriuretic and calciuretic response in the whole hypertensive group
      (n = 18, p < 0.001 and p < 0.05, respectively), while the examination of the
      individual excretion disclosed either exaggerated and appropriate or blunted
      urinary response. When the hypertensive group was classified in relation to salt
      sensitivity, the greater fall in mean arterial pressure during low salt diet
      (salt-sensitivity) was associated with the more pronounced natriuretic response
      during water immersion (r = -0.66, p < 0.003). An identical correlation (r = 
      0.58, p < 0.01) was also found between changes in mean arterial pressure (low
      salt diet) and urinary calcium excretion (water immersion) in the same
      hypertensives. The water immersion-induced suppression of plasma aldosterone and
      the increase in plasma atrial natriuretic peptide did result from comparable
      magnitude in the salt-sensitive and in salt-resistant subjects.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266006
TI  - Dose response dependency in regulation of acute PTH (1-84) release and
      suppression in normal humans: a citrate and calcium infusion study.
AB  - The aim of the present study was to investigate the possible dose response
      dependency of the very early changes in intact parathyroid hormone concentrations
      (PTH) on different rates of blood ionized calcium (B-Ca2+) lowering and raising.
      On 8 different days, four healthy volunteers received trisodium-citrate infusions
      at five different rates and calcium chloride infusions at three different rates,
      all of 10 min duration. S-PTH and B-Ca2+ were measured twice before each infusion
      and after 1, 2, 3, 4, 5, 7, and 10 min of infusion. The decrements of B-Ca2+
      expressed as area under the curve (AUC) correlated with the rate of trisodium
      citrate infusions (r = 0.97, p < 0.001) and furthermore, these B-Ca2+ decrements
      were matched by S-PTH increments expressed as AUC (r = 0.96, p < 0001).
      Multigroup comparisons on the results of protocol A showed statistical
      significant (p < 0.02). The increments of B-Ca2+ expressed as AUC correlated with
      the rate of calcium chloride infusions (r = 0.92, p < 0.001) and furthermore,
      these B-Ca2+ increments were matched by S-PTH decrements measured as AUC (r =
      0.95, p > 0.001). Multigroup comparisons on the results of protocol B showed
      statistical significant (p < 0.05). In conclusion, acute B-Ca2+ lowering and
      raising at different rates promotes stimulation and inhibition of the acute PTH
      release in rate dependent manner. For this mechanism being distinctly different
      from the steady state control of PTH secretion, we suggest the term 'delta
      regulation' (delta, i.e. the sign for change).

PMID- 8266007
TI  - Normocalcaemic hyperparathyroidism after parathyroidectomy: a retrospective
      study.
AB  - Forty-eight patients with proven hyperparathyroidism underwent parathyroidectomy.
      All patients were post-operatively normocalcaemic and free of symptoms due to
      their pre-operative hypercalcaemic state. However, 20 (42%) post-operative
      patients still had increased serum PTH and low serum phosphate levels.

PMID- 8266008
TI  - Within-subject variation of elastase/alpha 1-protease inhibitor complexes and
      lactoferrin in plasma.
AB  - Several studies have shown increased plasma concentrations of neutrophil elastase
      in complex with alpha 1-protease inhibitor and/or lactoferrin in inflammatory
      conditions, and serial measurements have been advocated in order to follow
      disease activity. However, data on the magnitude of the within-subject variation
      are necessary for evaluation of the significance of changes in results obtained
      on analysis of serial samples. Within-subject variation of elastase/alpha 1
      protease inhibitor complexes and lactoferrin over a short time was studied in six
      young men who had blood samples drawn every 4 h over 2 days. Within-subject
      variation over a longer time was investigated in 12 healthy adults, 6 females and
      6 males, who had blood samples drawn in the morning once a week for 10 weeks.
      From five of the females and five of the males, blood samples were also drawn
      every morning on 5 consecutive days during 1 week. Within-subject variations over
      hours, days, and weeks were estimated as 0.050, 0.124, and 0.148 for
      elastase/alpha 1-protease inhibitor complexes and as 0.101, 0.119, and 0.143 for
      lactoferrin. A tendency towards variation of LAC with menstrual cycle in fertile
      females was noticed. From within-subject variation, between-subject variation and
      analytical variation, indices of individuality were calculated as 1.1 and 1.8 for
      elastase/alpha 1-protease inhibitor complexes and lactoferrin, respectively. This
      means that within-subject variation for lactoferrin is quite small compared to
      between-subject variation, and the usefulness of reference limits is very
      limited, when interpreting results from individual patients. For elastase/alpha 1
      protease inhibitor complexes, the use of reference limits might be more
      appropriate, although still not optimal.

PMID- 8266009
TI  - Protein profile in bronchoalveolar lavage fluid from patients with sarcoidosis
      and idiopathic pulmonary fibrosis as revealed by SDS-PAGE electrophoresis and
      western blot analysis.
AB  - So far bronchoalveolar lavage (BAL)-protein in interstitial lung disease (ILD) is
      evaluated by measuring concentrations of single proteins. Due to the high
      dilution of most proteins in BAL, analysis of protein profile has been
      disappointing. This study describes a new method to overcome this problem and to
      reveal a highly differentiated picture of BAL proteins. Eighteen patients with
      pulmonary sarcoidosis, 18 patients with idiopathic pulmonary fibrosis (IPF) and
      22 patients with no clinical, roentgenologic or functional evidence of ILD
      underwent BAL. Total and differential cell count was performed. Normal values for
      the control group, a lymphocytic alveolitis in sarcoidosis and a granulocytic
      alveolitis in IPF-patients were found. Median total protein concentration in
      sarcoidosis showed an increase five times higher than that of the controls (150
      mg 1(-1) and 27 mg 1(-1), respectively) with p < 0.001, IPF protein concentration
      (58 mg 1(-1)) exceeded twice the control values (0.01 > p > 0.001). Analysis of
      electrophoretic protein profile in controls with Western blot analysis and the
      biotin/streptavidin staining system revealed a highly differentiated range of
      bands. Staining with immunoglobulin antibody identified six bands. Four proteins
      with molecular weight < 21.000 dalton were present only in sarcoidosis patients.
      These proteins may be identical with fragmented serum proteins or different cell
      mediators detected in alveolar cell supernatants. Furthermore, in sarcoidosis the
      intensity and number of bands with molecular weight more than 67.000 dalton was
      increased. This gives strong evidence for an injury of the alveolar membrane
      integrity in the alveolitis during the course of sarcoidosis.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8266010
TI  - Decrease of ischaemia-reperfusion related lung oedema by continuous ventilation
      and allopurinol in rat perfusion lung model.
AB  - Using isolated perfusion rat lung model, we studied the effect of continuous
      ventilation without perfusion and allopurinol on the development of ischaemia
      reperfusion lung injury. Ischaemia was induced by stopping the perfusion.
      Normothermic ischaemia for 90 min without ventilation caused significant lung
      oedema. Continuous ventilation during ischaemia with 21% O2 decreased lung oedema
      significantly after 60 min of reperfusion. The same protection could be achieved
      by 100% N2 ventilation during 90 min of ischaemia, suggesting that xanthine
      oxidase (XO) is unlikely to cause the ischaemia-reperfusion lung injury. On the
      other hand allopurinol, XO inhibitor, equally inhibited lung oedema after 90 min
      of ischaemia and 60 min of reperfusion. These results indicate that mechanical
      movement of alveoli provides successful preservation of ischaemic lung, and
      allopurinol has some protective effect other than XO inhibition.

PMID- 8266011
TI  - A clinical and biochemical study on tissue polypeptide antigen (TPA) in non
      malignant hepatic disorders.
AB  - The behaviour of the tumour marker TPA was studied in 160 patients with benign
      diffuse liver diseases which underwent a thorough clinical and biochemical
      evaluation. Abnormal serum levels were found in 71.9% of the 160 patients, 87.2%
      of the 86 cirrhotics, and 98.4% of the 61 cirrhotics with elevated aspartate
      aminotransferase (ASAT) levels. TPA correlated with numerous clinical and
      biochemical markers of liver disease, serum ASAT being the most significant one
      (r = 0.63, p < 0.00001). TPA values were higher in cirrhotics than in non
      cirrhotics (p < 0.0001) and in the patients with increased ASAT as compared with
      those with normal ASAT (p < 0.0001). In liver disease the cut-off level had to be
      raised five-fold to allow 10% abnormal values. This fact severely limits the
      usefulness of TPA in oncologic patients who also have liver disease. Cytolysis
      and/or liver regeneration appear to play an important role in the increase of TPA
      in these patients although other mechanisms such as impaired metabolism due to
      hepatocellular insufficiency also may be involved.

PMID- 8266012
TI  - Establishing reference values from adults: recommendation on procedures for the
      preparation of individuals, collection of blood, and handling and storage of
      specimens. Committee on Reference Values of the Scandinavian Society for Clinical
      Chemistry.
AB  - The concentrations of blood components are influenced by a number of
      preanalytical factors, the importance of which varies [1]. Therefore it is
      necessary to standardize the specimen collection, as was done by the Committee on
      Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical
      Physiology, which in 1975 published its recommendation on the production of
      reference values in clinical chemistry [2]. It was the very first recommendation
      of its kind. Since then, new information has accumulated, and it has become
      necessary to revise the part concerning the preparation of subjects for blood
      collection, the collection procedure itself, and the subsequent handling of the
      specimen. Also, The International Federation of Clinical Chemistry (Expert Panel
      on Theory of Reference Values) has produced its own recommendation [3]. The
      recommendation described below replaces pp. 39-44 of the former Scandinavian
      recommendation [2]. The procedure described below is designed for the collection
      of specimens for the measurement of the majority of components in blood and
      specimen collection from the cubital vein is described. It can be easily adapted
      for the collection of blood from other vessels [4]. Certain laboratory
      investigations require a special protocol. In that case, the preparation of the
      subject prior to and during specimen collection as well as the procedure itself
      should be described in sufficient detail to permit reproduction by adequately
      trained personnel. In any project designed to produce reference values the same
      protocol for the preparation of individuals and specimen collection should be
      used throughout the project. The protocol should be described in detail. Thus, it
      is not satisfactory to state only that the present recommendation was followed.
      Each section of the recommendation is followed by a check list for points which
      should be taken into account.

PMID- 8266013
TI  - Cyclosporin for inflammatory bowel disease: mechanisms and possible actions.

PMID- 8266014
TI  - Bile acid malabsorption in patients with chronic diarrhoea.
AB  - The presence of bile acid malabsorption was studied in 24 patients with chronic
      diarrhoea without established cause despite extensive investigations. Bile acid
      absorption was evaluated with the 75Se-homocholic acid taurine (SeHCAT) test. A
      therapeutic trial of cholestyramine was performed in 11 patients. Fourteen of the
      patients (58%) showed evidence of bile acid malabsorption. Of the 11 patients who
      were treated with cholestyramine, 3 had no improvement of their diarrhoea and
      also had a normal SeHCAT test result. Of the other eight patients, who also had
      pathologic SeHCAT test result, five improved on treatment, whereas three had no
      change of their diarrhoea. Seven of the 24 patients had a previous history of
      cholecystectomy. Four of them showed bile acid malabsorption; three of these were
      treated with cholestyramine and responded favourably. The results suggest that
      bile acid malabsorption may be common in chronic diarrhoea patients but may not
      always be the primary cause of diarrhoea.

PMID- 8266015
TI  - The Funen Adenoma Follow-up Study. Incidence and death from colorectal carcinoma
      in an adenoma surveillance program.
AB  - The results of a prospective randomized study of 1056 patients with colorectal
      adenomas are presented. After initial polypectomy from 1978 to 1992, patients
      were allocated at random to different follow-up intervals varying from 6 to 48
      months, except 53 patients who were allocated to intervals of 6 months. The
      examinations were mainly done by colonoscopy. Ten patients developed colorectal
      carcinoma, a number similar to that expected (7.96), when compared with a sex-
      and age-matched normal Danish population. The expected number of carcinomas was
      also calculated from adenoma to carcinoma conversion rates estimated in other
      studies and compared with that observed. If all carcinomas develop in large (> or
      = 10 mm) adenomas or adenomas with severe dysplasia, the expected number of
      carcinomas would have been 62 and 110, respectively, indicating a significant
      reduction of carcinomas in the present study. One patient died of colorectal
      carcinoma, which is significantly lower than the number expected (7.58). Two
      patients died of complications from therapeutic and diagnostic colonoscopy--that
      is, 2 deaths in 3959 colonoscopies. In conclusion, the follow-up strategy has
      resulted in a mortality from colorectal carcinoma which is reduced when compared
      with the normal population, in spite of an apparently similar incidence of
      carcinoma. However, previous suggested adenoma-carcinoma conversion rates
      indicate that a major reduction of incidence actually has taken place.

PMID- 8266016
TI  - Sulglycotide in the prevention of nonsteroidal anti-inflammatory drug-induced
      gastroduodenal mucosal injury. A controlled double-blind, double-dummy,
      randomized endoscopic study versus placebo in rheumatic patients.
AB  - The aim of this double-blind, randomized placebo-controlled trial was to evaluate
      whether sulglycotide prevents the onset of gastroduodenal mucosal injury in
      patients with rheumatic disease treated with nonsteroidal anti-inflammatory drugs
      (NSAIDs). One hundred patients, free from endoscopically detectable lesions of
      the gastroduodenal mucosa, affected either by rheumatoid arthritis or
      osteoarthritis, and candidates for NSAID therapy, were randomly allocated either
      to 200 mg sulglycotide three times daily (n = 50) or to an indistinguishable
      placebo (n = 50) for 4 weeks, together with standard NSAID administration (50 mg
      diclofenac three times daily (n = 50); 50 mg indomethacin three times daily (n =
      50)). Upper gastrointestinal endoscopy was repeated at the end of the study. It
      was possible to evaluate 86 patients after treatment (sulglycotide = 42, placebo
      = 44); diclofenac = 45, indomethacin = 41). Six of 42 patients (14%) in the
      sulglycotide group and 15 of 44 (34%) in the placebo group had developed gastric
      or duodenal ulcerative lesions (p = 0.02). These data suggest that sulglycotide
      prophylaxis may be useful for the prevention of gastric and duodenal ulcer
      associated with NSAID therapy in rheumatic patients.

PMID- 8266017
TI  - Effects of protein malnutrition on experimental giardiasis in the Mongolian
      gerbil.
AB  - To determine the effects of protein malnutrition on the severity and duration of
      infection with Giardia lamblia, Mongolian gerbils were pair-fed a pelleted
      control (C) diet (20% protein) and a low-protein (5%; LP) diet for 3 weeks before
      and after being infected with 100,000 cysts orally. Weight loss, fecal fat,
      enteropooling, and the duration of cyst excretion were all greater in the
      infected LP than in the infected C animals. During peak infection the upper
      intestinal intraepithelial lymphocyte infiltration, crypt enlargement, and villus
      enterocyte migration were greater in C than in LP animals, as was the villus mast
      cell number at the end of the infection. It is concluded that in the protein
      malnourished host the increased severity of Giardia infection correlates with a
      reduction in enterocyte production and migration, probably secondary to a reduced
      lymphocyte infiltration, and the increased infection duration correlates with
      blunted mast cell migration into affected villi.

PMID- 8266018
TI  - Green banana protection of gastric mucosa against experimentally induced injuries
      in rats. A multicomponent mechanism?
AB  - The protective capacities of fresh green (unripe) sweet bananas and of
      phosphatidylcholine and pectin (banana ingredients) against acute (ethanol- or
      indomethacin-induced) and chronic (indomethacin-induced) gastric mucosal lesions
      were evaluated in rats. Banana pulp was mixed with saline and given by gavage, as
      a pretreatment in a single dose. The identical protocol was used for pectin and
      phosphatidylcholine solution, and the dosages were adjusted to equal the amount
      of ingredients in the banana mixture, but higher concentrations were also given.
      The banana suspension reduced acute lesions, as did pectin and
      phosphatidylcholine in higher concentrations, but in concentrations as in fresh
      fruit no protective effects were observed except by pectin against indomethacin
      injury. In the model of chronic ulcers the banana suspension provided an
      incomplete and temporary protective effect. We conclude that the protective
      capacity of fresh green sweet bananas cannot be confined to only one active
      component. Pectin and phosphatidylcholine may protect gastric mucosa by
      strengthening the mucous-phospholipid layer, but the mechanism of protection
      afforded by bananas has to be further elucidated.

PMID- 8266019
TI  - Biotinidase activity in patients with liver disease.
AB  - To investigate whether biotinidase deficiency may occur in liver disease, we
      determined biotinidase activity, biotin levels, and organic acids in patients
      with liver disease. Serum biotinidase activity in patients with liver disease
      (2.63 +/- 1.40 nmol/min/ml) was significantly lower than in the control group
      (5.43 +/- 1.06 nmol/min/ml). Serum biotinidase activity in decompensated liver
      cirrhosis (LC) and hepatoma was significantly lower than in acute viral hepatitis
      (AVH), chronic viral hepatitis (CVH), and compensated LC. The mean serum level of
      biotin in decompensated LC (1.8 +/- 0.6 microgram/ml) and hepatoma (1.7 +/- 0.8
      microgram/ml) was significantly lower than in the control group (2.5 +/- 1.0
      microgram/ml), and urinary excretion of biotin was increased in patients with
      liver disease, particularly in decompensated LC. Biotinidase activity correlated
      positively with serum biotin level and correlated negatively with urinary biotin
      level. Moreover, in four of five patients with severe liver disease the excretion
      of propionate, lactate, and 3-hydroxybutyrate decreased after biotin
      supplementation. The data for patients with severe liver disease so resembled
      those for late-onset multiple carboxylase deficiency that biotinidase deficiency
      is likely in patients with severe liver disease.

PMID- 8266020
TI  - Inhibitory effects of terbutaline on human esophageal peristalsis and development
      of tolerance.
AB  - To investigate the inhibitory influence on esophageal motility of prolonged beta
      2-adrenergic stimulation, esophageal peristalsis was studied in 10 volunteers.
      The beta-2 agonist terbutaline was given orally, 5 mg three times daily, for 10
      days, and the subjects were studied before medication (basal), on days 3 and 10
      during the medication, and 1 week after withdrawal of the drug. At each session
      esophageal peristaltic pressure, heart rate, and finger tremor were assessed. On
      the 3rd day of medication the peristaltic pressure was significantly decreased
      and heart rate and finger tremor significantly increased compared with basal
      values on day 0. On the 10th day of medication there was still a decrease in
      peristaltic pressure but less pronounced than on day 3 despite similar blood
      levels of terbutaline. It is concluded that oral medication with a beta-2 agonist
      initially inhibits esophageal peristalsis, but during continued medication the
      inhibitory effect on the esophagus decreases. The results indicate development of
      esophageal tolerance to beta-2-receptor stimulation in accordance with
      development of tolerance shown in extraintestinal organs.

PMID- 8266021
TI  - The correlation of symptoms, occult blood tests, and neoplasms in patients
      referred for double-contrast barium enema.
AB  - One hundred and forty-nine patients (86 women) with a mean age of 64 years (52-74
      years), referred for double-contrast barium enema (DCE), were invited to have
      fecal occult blood test and rectosigmoidoscopy (60 cm) (RSS) before the DCE.
      Carbon dioxide was used for inflation at RSS to enable the two examinations to be
      done at the same time. Eight adenomas < 1.0 cm in diameter, 11 adenomas > or =
      1.0 cm in diameter, and 5 carcinomas were diagnosed in altogether 23 patients.
      There was no correlation between symptoms, diverticula, or neoplasm, but a
      positive rehydrated Hemoccult II test was correlated to the presence of neoplasms
      (cancer and adenoma > or = 1.0 cm in diameter), but Hemoccult is not suitable as
      selection basis for work-up of symptomatic subjects. To diagnose colorectal
      neoplasms, we have to accept a certain number of negative work-ups of the large
      bowel. If DCE is chosen for work-up of the large bowel, it has to be combined
      with rectosigmoidoscopy (60 cm).

PMID- 8266022
TI  - An in vitro study of enhanced H+ diffusion by urease action on urea. Implications
      for Helicobacter pylori-associated peptic ulceration.
AB  - The in vitro effect of urea and hydrolysis of urea by urease on mucus H+
      permeability is reported here. The effective DHCl values indicate a strong pH
      dependence for H+ diffusion in both water and mucus layers, with no apparent
      trend at concentrations between 1 and 50 mM urea. However, the estimated DHCl at
      near-neutral and alkaline pH are 4- to 10-fold lower through mucus than through
      aqueous films. Moreover, the pKa values of HCO3- and NH3 (generated by urease
      action on urea) had a profound effect on measured DHCl. These in vitro studies
      suggest that a high local concentration of NH3 and HCO3- within the mucus layer,
      generated by the action of Helicobacter pylori urease on endogenous intragastric
      urea, could greatly accelerate proton flux to the surface epithelium by operation
      of a buffer shuttle. This results in enhanced H+ permeability, particularly at
      pKa values of HCO3- and NH3, and in extreme circumstances it may result in
      gastric ulcer formation.

PMID- 8266023
TI  - Is duodenal bile representative of gallbladder bile? A comparative study.
AB  - Thirty-nine patients with cholelithiasis were prospectively studied to evaluate
      the qualitative and quantitative differences between duodenal bile and
      gallbladder bile. Duodenal bile obtained before cholecystectomy by nasoduodenal
      intubation and ceruletide injection was qualitatively similar to gallbladder bile
      obtained during surgery. Microscopic cholesterol crystals as an indicator of
      cholesterol gallstones (n = 35) could be detected in 31 (89%) and 35 (100%; p =
      NS), respectively. Moreover, there was no difference in the molar percentage of
      three biliary lipids and the mean cholesterol saturation index (1.54 +/- 0.72 and
      1.74 +/- 0.42; p = NS) of the two sources of bile. Duodenal bile was, however,
      dilute as compared with gallbladder bile, as evidenced by lower cholesterol
      crystal counts (167 +/- 247 versus 705 +/- 978; p < 0.01), lower total lipid
      concentration (5.8 +/- 2.7 versus 11.1 +/- 5.6 g/dl; p < 0.001), and lower
      concentrations (in mmol/l) of the three bile lipids--that is, total bile acids,
      phospholipids and cholesterol (p < 0.001). Good concentrated bile (total lipid
      concentration > or = 5 g/dl) could be obtained in 74% of duodenal bile samples,
      compared with 90% of gallbladder bile (p = NS). Our study shows that, although
      duodenal bile is dilute as compared with gallbladder bile, it is qualitatively
      similar to gallbladder bile and, because of the ease and safety of its
      collection, can be used to study serial alterations in biliary composition in
      individual subjects.

PMID- 8266024
TI  - Intestinal metaplasia, not atrophy or achlorhydria, creates a hostile environment
      for Helicobacter pylori.
AB  - A 54-year-old man with dyspepsia, Helicobacter pylori-associated chronic active
      atrophic gastritis without intestinal metaplasia, and hyperplastic gastric polyps
      was followed up for 1 year after H. pylori eradication with sequential endoscopic
      gastric mucosal mapping and gastric function tests. Eradication of H. pylori by
      triple therapy resulted in the histologic resolution of gastritis. However, the
      patient's condition, gastric function, and morphology of the polyps were not
      affected. This case illustrates that: a) in the absence of intestinal metaplasia,
      H. pylori can infect the stomach with gastric atrophy; b) the absence of acid
      does not preclude H. pylori infection; c) advanced atrophic gastritis may be an
      irreversible condition; and (d) the neutrophilic infiltrate in hyperplastic
      polyps is independent of the presence of H. pylori.

PMID- 8266025
TI  - The effects of tobacco sales promotion on initiation of smoking--experiences from
      Finland and Norway.
AB  - Norway and Finland were among the first countries to adopt a total ban on tobacco
      sales promotion. Such legislation came into force in Norway and Finland in 1975
      and 1978 respectively. These two countries are sometimes referred to as
      illustrations that such legislation has been successfully used as a means to
      reduce tobacco consumption. Tobacco industry spokesmen seem to interpret
      available evidence in the opposite way and maintain that the prohibition has not
      contributed to reducing the use of tobacco. Among the publications referred to
      and misused by tobacco industry spokesmen are publications from the authors of
      the present report. The effects of a ban on advertising can only be properly
      examined after describing a reasonable conceptual model. Such a model has to take
      into account (i) other social and cultural predictors of smoking, (ii) tobacco
      sales promotion in the contexts of all other mass communication, (iii) control
      measures other than a ban, and (iv) the degree of success in implementing the ban
      on advertising. Like any other kind of mass communication tobacco advertising
      influences the individual in a rather complex way. Behaviour change may be
      regarded as the outcome of an interpersonal and intrapersonal process. Social
      science research on tobacco advertising and the effects of banning such
      advertising has a short history, most studies having been carried out in the late
      1980s. After examining available evidence related to the effects of tobacco
      advertising on the smoking habits of adolescents we conclude as follows: the few
      scientifically valid reports available today give both theoretical and empirical
      evidence for a causal relationship. Tobacco sales promotion seems both to promote
      and to reinforce smoking among young people. The dynamic tobacco market
      represented by children and adolescents is probably the main target of tobacco
      sales promotion. In Finland, there have been few studies explicitly addressing
      the causal links between tobacco sales promotion and the smoking habits of
      adolescents. In Norway, no such studies have been carried out. If we examine the
      changes in the use of tobacco over time, the data available do not lend support
      to the conclusions drawn by the tobacco industry spokesmen. In Norway the
      prevalence of daily smokers was higher in 1975, when the ban on tobacco
      advertising came into force than either before or after. The strongest decrease
      in the prevalence of daily smokers took place during the first five-year period
      after the ban was introduced.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8266026
TI  - Meta-analysis of NSAIDs: contribution of drugs, doses, trial designs, and meta
      analytic techniques.
AB  - To elucidate potential bias sources in meta-analyses, I studied whether the
      effect of nonsteroidal, anti-inflammatory drugs on joint count in patients with
      rheumatoid arthritis was related to trial design (active or placebo control),
      sample size, duration of treatment, drop-out rate, the existence of a wash-in
      period, drug, dose, and meta-analytic technique. In short-term trials, none of
      the covariates was related to the effect size. No differences between drugs or
      doses were found in usual gold standard meta-analyses, comparing drugs within
      trials before pooling. In a meta-analysis of treatment arms, however, four drugs
      were either significantly more or less effective than average, but these
      deviations were spurious. In meta-analyses of NSAIDs, indirect comparisons may
      allow a preliminary comparison of drugs that have not been compared directly.
      Treatment arms should be compared within trials before pooling, however.

PMID- 8266027
TI  - Use of anti-thymocyte globulin in the management of refractory systemic
      autoimmune diseases.
AB  - The purpose of our pilot study was to evaluate the short-and long-term efficacy
      of T-lymphocyte depletion in the management of patients with refractory, systemic
      autoimmune diseases. Nine patients with severe, therapy-resistant autoimmune
      diseases were subjected to T-cell depletion procedure using polyclonal anti-T
      cell antibodies combined with peroral administration of azathioprine and/or
      cyclosporine. The proband group consisted of 4 patients with systemic lupus
      erythematosus, 3 with progressive systemic sclerosis, and 2 with rheumatoid
      arthritis. Administration of polyclonal anti-T-cell antibodies was performed at a
      single occasion via a central venous catheter during 9-10 days. Immunological
      analyses of T-cell phenotypes and function and assessment of organ function
      (kidneys, lungs, bone-marrow) has been performed prospectively in all the
      patients studied. This treatment resulted in prompt and long-lasting (mean follow
      up time: 25.6 months) improvement of autoimmune hemolytic anemia,
      glomerulonephritis, lung fibrosis, skin and joint involvements in the majority of
      cases. Adverse effects of this treatment included two episodes of infection (E.
      coli and Cytomegalovirus) and three cases of serum sickness, and were all easily
      managed. We suggest that this treatment modality adopted from transplant
      rejection therapy could be employed in cases of severe autoimmune diseases
      unresponsive to regular immunosuppressive treatment.

PMID- 8266028
TI  - Natural killer cell cytotoxicity and alpha-interferon in early rheumatoid
      arthritis.
AB  - Natural killer (NK) cell number, cytotoxicity, and serum alpha-interferon (alpha
      IFN) was measured in a group of early synovitis patients and compared to that of
      established rheumatoid arthritis patients and normal controls. No significant
      differences in NK cell number or serum alpha-IFN were found. NK cell cytotoxicity
      (NKCC) in the early synovitis group was significantly (p < 0.05) reduced compared
      to that of the normal controls and not significantly different from the
      established rheumatoid controls. There was a trend for those early synovitis
      patients with a good outcome to have higher NKCC. Low NKCC is evident very early
      in the course of rheumatoid arthritis and is thus unlikely to be secondary to
      chronic inflammation. There is no relationship between NKCC and alpha-IFN levels
      and the cause of the reduced NKCC is unknown. Alpha-IFN levels are not raised
      early in the course of RA.

PMID- 8266029
TI  - Gm phenotype linkage to subsets of juvenile chronic arthritis (JCA) with
      influence on IgG subclass response.
AB  - The serum hyper IgG of 76 JCA patients of different clinical subsets, 8 systemic,
      37 polyarticular and 31 oligoarticular, were investigated by IgG subclass
      quantitation and Gm allotype determination. The well known increased serum IgG in
      JCA was confirmed as increased IgG1, IgG2 and IgG3 in the whole group.
      Investigating the clinical subsets IgG1 was significantly increased in all
      subsets while IgG2 and IgG3 increased only in the polyarticular form. In search
      of a genetic linkage for the clinical JCA subsets and the different IgG subclass
      patterns found, the alternative Gm allotypes G1m(a), G1m(f) for IgG1, G2m(n),
      G2m(") for IgG2 and G3m(g) , G3m(b) for IgG3 gene loci were investigated. The Gm
      (a,",g) haplotype was significantly increased in the whole JCA group and in the
      polyarticular subset. In the systemic subset the Gm (a,",g/a",g) phenotype was
      significantly increased, but the Gm (a,'h,g/f,n,b) phenotype was increased in the
      oligoarticular subset. The number of JCA patients with G1m(f,f)-,G3m(b,b)
      phenotypes were significantly decreased. In such phenotypes, remission was more
      common. The susceptibility of JCA, its different clinical subsets and outcome of
      the disease is determined by Gm allotypes, affecting characteristic IgG subclass
      patterns.

PMID- 8266030
TI  - Incidence and survival rate in cases of biopsy-proven temporal arteritis.
AB  - In the population of the city of Tampere, Finland, 66 patients with
      histologically verified temporal arteritis were identified during the 20-year
      period from 1969 to 89. The cases were followed up to March 31st in 1991. The
      annual age- and sex-adjusted incidence of temporal arteritis per 100,000
      population aged 50 or older was 4.5 in 1970-79 and 9.2 in 1980-89. The patients
      showed excess mortality although this was not statistically significant. After
      excluding hypertensive disease, angina pectoris and congestive heart disease the
      survival of the remaining subgroup did not differ from the control population.

PMID- 8266031
TI  - Analysis of the outcome of idiopathic inflammatory myopathies with particular
      emphasis on muscle capillary damage.
AB  - The objective of this study was to assess the outcome of our series of idiopathic
      inflammatory myopathies (IIM) with special consideration of capillary damage as a
      prognostic indicator. We have classified our series of patients with the
      diagnosis of IIM according to the presence or absence of capillary damage in
      muscle biopsies, and determined their outcome by means of survival analysis
      statistical techniques. The follow-up of our patients seems to demonstrate that
      the patients without capillary damage present a more indolent form of IIM, with a
      slower response to treatment. The presence of capillary damage indicates a more
      acute disease, with more morbidity and mortality, but with a faster response to
      immunosuppression. The presence or absence of capillary damage seems to determine
      two forms of IIM with differentiated outcome and prognostic.

PMID- 8266032
TI  - Lambert-Eaton myasthenic syndrome associated with Sjogren's syndrome and discoid
      lupus erythematosus.
AB  - A 65-year-old woman with facial erythema and hypergammaglobulinemia developed
      excessive fatigability. A diagnosis of Lambert-Eaton myasthenic syndrome (LEMS)
      was made from electrophysiological studies. She had symptoms and laboratory data
      compatible with probable Sjogren's syndrome. Skin biopsy revealed the
      histological findings of discoid lupus erythematosus. Treatment with 3,4
      diaminopyridine resulted in the improvement of fatigability. LEMS should be
      recognized as a treatable complication of systemic autoimmune diseases.

PMID- 8266033
TI  - [Endocrine tumors of the pancreas. Status of the question].
AB  - Progress in radioimmunology and immunohistochemistry and the use of
      intraoperative ultrasonography has considerably improved the diagnosis of
      endocrine tumors. These advances have changed the prognosis of these tumors since
      the outcome directly depends on early diagnosis. Surgery is the treatment of
      choice, in many cases even in the presence of hepatic metastasis. Medical
      treatment should be used when surgery is contraindicated and includes cytostatic
      agents (e.g. streptozotocin, 5-FU) or interferons and drugs preventing hormone
      release such as long-acting somatostatin analogs (SMS 201-995). Finally,
      symptomatic treatment alone should be confined to cases of unresectable tumors
      with diffuse metastasis.

PMID- 8266034
TI  - [Association between lipoprotein(a) and coronary disease].
AB  - The relationship of serum lipoprotein(a) [Lp(a)] to ischemic heart disease was
      investigated in a series of 114 men undergoing elective diagnostic coronary
      angiography at the University Hospital of Lausanne (Switzerland). Serum Lp(a) was
      higher (median: 134 mg/l; mean +/- SD: 371 +/- 509 mg/l) in the 76 individuals
      with ischemic heart disease, as defined by at least one significant stenosis (>
      or = 50%) in a proximal segment of a major coronary artery, compared to the 38
      individuals without significant stenosis (60 mg/l; 155 +/- 218 mg/l). The risk
      ratio for ischemic heart disease was 4.2 (95% CI: 1.05-16.6) for serum Lp(a)
      greater than 300 mg/l compared to concentrations smaller than 50 mg/l, after
      adjustment for total cholesterol, HDL-cholesterol, body mass index, cigarette
      smoking, hypertension, and age. Lp(a) was the strongest lipid correlate of a
      severity score for coronary atherosclerosis (Jenkins' score) after adjustment for
      the other considered risk factors (partial R squared = 0.10; p < 0.001). These
      data are consistent with a strong independent effect of Lp(a) on ischemic heart
      disease. The literature on Lp(a) is reviewed and a clinical approach proposed.

PMID- 8266035
TI  - [Furuncular myiasis].

PMID- 8266036
TI  - [The effect of lowering cholesterol on mortality].
AB  - There is little doubt about the validity of the lipid hypothesis as a
      pathogenetic theory for atherosclerosis. However, this theory does not allow the
      conclusion that cholesterol-lowering treatment is necessarily beneficial in
      practice. As a consequence of the probabilistic nature of risk factors, the
      classification of plasma cholesterol levels into "normal" and "pathological" can
      be misleading in clinical practice. The potential benefit of cholesterol-lowering
      treatment is a direct function of the overall coronary risk, more or less
      independently of plasma cholesterol. Therefore, plasma cholesterol is of clinical
      significance only in patients with established CHD and a high overall risk of
      infarction. Total mortality has been prospectively included as one end-point in
      addition to infarct mortality in the many intervention studies on cholesterol
      lowering. Meta-analyses of these studies show a non-significant decrease in
      infarct mortality through cholesterol-lowering drug treatment, with a
      concomitant, highly significant increase in non-infarct mortality. Lowering
      cholesterol in asymptomatic persons and in coronary patients with a relatively
      low risk of infarction results in a significant increase in total mortality. Only
      in a very small group of coronary patients with a very high risk of myocardial
      infarction, due to the presence of several additional risk factors, may
      cholesterol-lowering treatment be beneficial.

PMID- 8266037
TI  - [Enuresis in childhood: what should one know? What should one do?].
AB  - Bladder control is a developmental process which is determined by somatic,
      individual psychological and psychosocial factors. It depends on the maturation
      of bladder capacity and of adequate neuromuscular coordination, on the quantity
      of urine and on appropriate recognition of bladder expansion. The latter
      especially is clearly correlated to healthy individuation and psychosocial
      integration of the child. Statistically, 80-90% of children have successfully
      developed bladder control at the age of 4-6 years. In the remaining 10 or 20% who
      do not attain dryness during daytime or at night, wetting is often felt to be
      disturbing state, sometimes more by the parents than by the children. The state
      is called enuresis. The physician is expected to master the problem of night or
      daytime enuresis diagnostically as well as therapeutically. Although in most
      cases enuresis represents a retardation of normal development, it is important
      not to miss the rare, but, if present, important disturbing factors. Disorders
      can occur at all above mentioned levels, either in isolation or combined.
      Although proposing the simplest diagnostic measures, the present paper represents
      an optimal workup during which none of the rare somatic or complicated
      psychological disturbances, which would need specialized attention, should be
      missed. After this workup the therapeutic pathways are clear. On the one hand,
      relevant somatic and/or psychological disorders must be treated specifically
      (often in collaboration with the specialist). On the other side, there is the
      large number of enuretics who are, by all criteria, normal children. In these it
      is possible to accelerate the developmental process by performing an elaborate
      micturition protocol which has a good chance of success, provided, however, there
      is optimal cooperation between physician, parents and child.

PMID- 8266038
TI  - [An expedient solution in the area of dental benefits].

PMID- 8266039
TI  - [The effect of ultrasonic condensation on gold condenser fillings and on the
      abutting dental hard tissue].
AB  - A prototype ultrasonic condensation device was applied to condense two class V
      mat-gold fillings in each of 10 extracted molars (group A). For 10 other molars a
      conventional electric device was used (group B). In five molars of each group the
      nib face of the condenser was not brought into direct contact with the cavity
      margins (AI/BI); in the other five molars of the sample this was done
      intentionally (AII/BII). Only one of the two fillings in each tooth was polished.
      Replicas of the fillings were examined for marginal adaptation by means of
      scanning electron microscopy (SEM). After dye penetration for 24 h, ground
      sections of the teeth were examined by light microscopy and SEM. Enamel cracks
      and cementum injuries were predominantly observed in unpolished fillings of group
      AII and BII. The marginal adaptation in group AI was significantly better than in
      group AII, BI, BII, respectively. The polished fillings demonstrated a
      significantly lower incidence of dye penetration than unpolished restorations.
      Our results indicate that only direct treatment of the cavity margins with the
      ultrasonic device causes enamel cracking and cementum injuries. Avoidance of
      direct treatment of the cavity margins seems to result in better marginal
      adaptation. In addition to that, polishing seems to lead to lower rates of
      microleakage.

PMID- 8266040
TI  - [Fluoride gels--local application with a tray or a toothbrush?].
AB  - Fluoride gels have been used since the 1960s. Most gels are recommended for use
      in mouth-trays. An alternative is the application on a toothbrush. The present
      study compared the fluoride concentration in surface enamel and its acid
      resistance following the application in a tray or on a toothbrush in vitro. In a
      first experiment 80 halves of molar crowns were used. In group A 20 were coated
      with fluoride gel. In group B 20 were brushed with gel. 20 each served as water
      control. The surface fluoride concentration and acid resistance of all samples
      were assessed using an acid etch technique. In a second experiment 30 halves of
      molar crowns were used. 10 were mounted in a plaster socket mimicking a dental
      arch for which a customized miniplast-tray was made. This tray was loaded with 1
      g of gel and applied for 3 min on 3 consecutive days. 10 samples were brushed for
      3 min on 3 days using 1 g of gel and 10 served as water control. Enamel that had
      been fluoridated with gel on a toothbrush showed a superior acid resistance. The
      fluoride concentration in the outer 20 to 25 microns of enamel was higher after
      gel application on a toothbrush than after tray application.

PMID- 8266041
TI  - [Magnetic resonance microscopy--new prospects for endodontics].
AB  - With the use of magnetic resonance microscopy (MRM) the options and limitations
      of this modern technique in reproducing teeth and endodontium should be
      evaluated. Therefore, extracted teeth were stored in formaline and measured in
      two different devices of the magnetic resonance technique. One is common for
      material research and normally used for spectroscopy of solids. Measuring takes
      place in the strayfield of the magnet which leads to the term "Stray Field
      Imaging" (STRAFI). The other one is a spectroscopy with an additional micro
      imaging device (magnetic resonance microscope) where resolutions up to (100
      microns)3 can be reached. For the first time the STRAFI allowed to make pictures
      from the hydrogen-protons of the teeth's hard substances. A two or three
      dimensional imaging on the basis of microscopic resolution became reality. In
      addition the MRM allowed to depict the soft tissue portion and the outer contour
      of the teeth in 2D and 3D. The two-dimensional pictures were able to show a
      texture within the pulp tissue. The three-dimensional images enabled a
      naturalistic and non-destructive visualization of the outer surface and the pulp
      room. The results shown here open very new perspectives for endodontics.

PMID- 8266042
TI  - [The surface conditioning of pressed ceramics and its effect on the bond strength
      to composites].
AB  - After removal of the investment material, unpolished surfaces of pressed glass
      ceramics (Empress) are covered by a layer containing magnesium and phosphorus.
      This layer most likely results from the contact with the investment material
      during pressing. Following short-time conditioning with 5% HF-gel the superficial
      layer stays amorphous. After etching for 120 s most of the surface layer is
      removed revealing the fine grained etching pattern characteristic for this type
      of ceramics. Shear strength of composite luted to unetched pressed ceramic
      samples was rather low. After etching for 60 s bond strength was considerably
      higher, but only following 120 s of etching shear strength reached a level
      comparable to that of ground pressed samples and ground ingots after 60 s of
      etching. Since mechanical removal of the surface layer by grinding is not
      recommended, pressed glass ceramics should be etched for 120 s or longer to
      achieve an optimal bond strength to the luting composite.

PMID- 8266043
TI  - [Central giant-cell granuloma. A review and case reports].

PMID- 8266044
TI  - [Anorexia and bulimia. The eating disorders anorexia nervosa and bulimia nervosa
      and oral health].

PMID- 8266045
TI  - [Unavoidable diseases as compulsory benefits. The revision of the health
      insurance law].

PMID- 8266046
TI  - [Dental caries and tooth loss up to the year 2008: the prognoses for 25- to 65
      year-old adults].

PMID- 8266047
TI  - [Fluoride and fluoridation. The Federation Dentaire International].

PMID- 8266048
TI  - [The Tox-Center offers comprehensive service benefits].

PMID- 8266049
TI  - [The Dental Institute of the University of Zurich over the course of time].

PMID- 8266050
TI  - [Hepatic necrosis caused by Clostridium perfringens in a dog].
AB  - A case of acute hepatic necrosis in a dog is clinically and pathologically
      described. The occurrence of Clostridium perfringens in the liver lesions was
      revealed by histological examination and bacteriological isolation. Based on
      these findings we conclude that Clostridium perfringens is the cause of the
      infarcts. The case is discussed on the base of the literature.

PMID- 8266051
TI  - [Uterine motility of cattle during late pregnancy, labor and puerperium. III. Use
      of flunixin meglumine and endocrine changes].
AB  - In the present study the effect of Flunixin meglumine (FM), a cyclooxygenase
      inhibitor, was investigated on postpartal prostaglandin production and uterine
      activity in the cow. For that purpose 8 cows were given FM in a dose of 2.2 mg/Kg
      b.w. twice daily (08.00 and 16.00 h) for the first 10 days p.p. Blood samples
      were collected at various times before, during and after parturition and the
      concentrations of 15-keto-13,14-dihydro-PGF2 alpha (PGFM), progesterone as well
      as adrenaline and noradrenaline determined. Eight cows served as controls.
      Uterine activity was measured by means of pressure microsensors and electrodes
      which were surgically implanted into the uterine wall before parturition. During
      the whole treatment period FM inhibited endogenous PG-production by more than 80%
      (p < 0.05). The suppressive effect of FM was maximal 4 h after the last injection
      and lasted no longer than 8 h. PGF2 alpha-suppression clearly decreased
      spontaneous uterine motility and reduced the myometrial response to ocytocin (5
      IU i.v.) and PGF2 alpha (15 mg i.v.). Treatment with FM did not interfere with
      uterine involution, the return to cyclicity and the first postpartal cycle
      length. Also, no obvious effects were seen on catecholamine concentrations which
      fluctuated during parturition without regularly representing the actual stress
      situation. Our results demonstrate that FM is able to effectively inhibit PGF2
      alpha-secretion as well as uterine activity in the cow. Further evaluation of FM
      as a tocolyticum or in the treatment of uterine infections is required.

PMID- 8266052
TI  - Clinical signs, diagnosis and treatment of duodenal ileus in cattle.
AB  - The clinical signs, changes in blood and rumen fluid, findings at laparotomy,
      therapy and course of disease of 23 cows with obstruction or compression of the
      duodenum are described. The duodenum was obstructed by a phytobezoar in 14 cows
      and by a blood clot in one cow. In eight cows, the duodenum was compressed by and
      adhered to a liver abscess. The most important clinical findings included
      moderate to severe disturbance in the general behaviour and attitude, markedly
      reduced gastrointestinal activity, no or greatly reduced defaecation and abomasal
      reflux with metabolic alkalosis. Ten cows were slaughtered after clinical
      examination or exploratory laparotomy. In 13 cows, the phytobezoar was compressed
      manually to facilitate normal elimination, and if this was not possible, the
      phytobezoar was removed by enterotomy. Postoperative therapy consisted of
      intravenous administration of a solution containing sodium chloride and glucose,
      potassium chloride and intramuscular administration of metoclopramide, procaine
      penicillin and flunixin meglumine for three to five days. Two of the treated cows
      were slaughtered a few days postoperatively. There was a rapid improvement in the
      remaining 11 cows, and general condition, appetite and defaecation returned to
      normal within a short time.

PMID- 8266053
TI  - [Efficacy of the oral antiparasitic mebendazole plus trichlorfon (telmin plus
      trichlorfon) against Gasterophilus in the horse].
AB  - The combined drug Mebendazole plus Trichlorfon (Telmin plus Trichlorfon, Janssen
      Pharmaceutica, Beerse/Belgium) has been tested in a field trial against naturally
      acquired Gasterophilus spp. infestations in horses. 44 foals (1 to 1.5 years old,
      350-450 kg body-weight) originating from different endemic areas of Switzerland,
      have been randomly allocated to two groups as follows: 28 foals were treated with
      Mebendazole plus Trichlorfon, 16 animals served as untreated controls. The drug
      (paste) was administered and dosed according to the user's instruction.
      Macroscopic examinations of the digestive tractus and the larval counting has
      been performed immediately after slaughtering, i.e. 30 and 33 days after
      treatment, resp.. The efficacy of the product against Gasterophilus spp. amounts
      to 97.04% which is considered as highly effective. A further proof for the high
      efficacy is the observation of a lot of larvae-carrying foals in the control
      group. Since the larvae of Gasterophilus spp.--according to their life cycle--are
      essentially found in their hosts between November and February, an appropriate
      treatment should be performed during that period of time.

PMID- 8266054
TI  - [Alternative medicine: a "specialty" for the veterinarian? An opinion from the
      viewpoint of the veterinary school].

PMID- 8266055
TI  - Multiple sensitivities.

PMID- 8266056
TI  - Coupled oscillators and biological synchronization.

PMID- 8266057
TI  - Deliverance. Medicine closes in on an artificial liver device.

PMID- 8266058
TI  - Fractured functions. Does the brain have a supreme integrator?

PMID- 8266059
TI  - A joycean mutation. Researchers discover a new mechanism for cancer.

PMID- 8266060
TI  - The fertility decline in developing countries.

PMID- 8266061
TI  - MHC polymorphism and human origins.

PMID- 8266062
TI  - Drugs by design.

PMID- 8266063
TI  - M.D.-Ph.D. degrees.

PMID- 8266064
TI  - Conflict of interest.

PMID- 8266065
TI  - M.D.-Ph.D. degrees.

PMID- 8266066
TI  - Scandal scars Minnesota Medical School.

PMID- 8266067
TI  - New bind for ulcer bacterium.

PMID- 8266068
TI  - 'Bubble boy' paradox resolved.

PMID- 8266069
TI  - AIDS vaccine research. A new goal: preventing disease, not infection.

PMID- 8266070
TI  - Two jobs for the origin replication complex.

PMID- 8266071
TI  - Origin recognition complex (ORC) in transcriptional silencing and DNA replication
      in S. cerevisiae.
AB  - In Saccharomyces cerevisiae, the HMR-E silencer blocks site-specific interactions
      between proteins and their recognition sequences in the vicinity of the silencer.
      Silencer function is correlated with the firing of an origin of replication at
      HMR-E. An essential gene with a role in transcriptional silencing was identified
      by means of a screen for mutations affecting expression of HMR. This gene, known
      as ORC2, was shown to encode a component of the origin recognition complex that
      binds yeast origins of replication. A temperature-sensitive mutation in ORC2
      disrupted silencing in cells grown at the permissive temperature. At the
      restrictive temperature, the orc2-1 mutation caused cell cycle arrest at a point
      in the cell cycle indicative of blocks in DNA replication. The orc2-1 mutation
      also resulted in the enhanced mitotic loss of a plasmid, suggestive of a defect
      in replication. These results provide strong evidence for an in vivo role of ORC
      in both chromosomal replication and silencing, and provide a link between the
      mechanism of silencing and DNA replication.

PMID- 8266072
TI  - Yeast origin recognition complex functions in transcription silencing and DNA
      replication.
AB  - The genes encoding two of the subunits of the Saccharomyces cerevisiae origin
      recognition complex (ORC) have been isolated. Characterization of a temperature
      sensitive mutation in the gene encoding the 72-kD subunit of ORC (ORC2) indicates
      that this protein complex functions early in the DNA replication process.
      Moreover, ORC derived from orc2ts cells is defective for DNA binding. Others have
      shown a defect in orc2ts cells in transcriptional silencing at the silent mating
      type loci. Consistent with this finding, ORC specifically binds to each of the
      four mating-type silencers identified in yeast. These findings support the
      hypothesis that ORC acts as an initiator protein at yeast origins of DNA
      replication and suggest that ORC also functions in the determination of
      transcriptional domains.

PMID- 8266073
TI  - The crystal structure of lysin, a fertilization protein.
AB  - Lysin, a protein from abalone sperm, creates a hole in the envelope of the egg,
      permitting the sperm to pass through the envelope and fuse with the egg. The
      structure of lysin, refined at 1.9 angstroms resolution, reveals an alpha
      helical, amphipathic molecule. The surface of the protein exhibits three
      features: two tracks of basic residues that span the length of the molecule, a
      solvent-exposed cluster of aromatic and aliphatic amino acids, and an extended
      amino-terminal hypervariable domain that is species-specific. The structure
      suggests possible mechanisms of action.

PMID- 8266074
TI  - A functional recombinant myosin II lacking a regulatory light chain-binding site.
AB  - Myosin II, which converts the energy of adenosine triphosphate hydrolysis into
      the movement of actin filaments, is a hexamer of two heavy chains, two essential
      light chains, and two regulatory light chains (RLCs). Dictyostelium myosin II is
      known to be regulated in vitro by phosphorylation of the RLC. Cells in which the
      wild-type myosin II heavy chain was replaced with a recombinant form that lacks
      the binding site for RLC carried out cytokinesis and almost normal development,
      processes known to be dependent on functional myosin II. Characterization of the
      purified recombinant protein suggests that a complex of RLC and the RLC binding
      site of the heavy chain plays an inhibitory role for adenosine triphosphatase
      activity and a structural role for the movement of myosin along actin.

PMID- 8266075
TI  - Isolation of ORC6, a component of the yeast origin recognition complex by a one
      hybrid system.
AB  - Here a method is described to identify genes encoding proteins that recognize a
      specific DNA sequence. A bank of random protein segments tagged with a
      transcriptional activation domain is screened for proteins that can activate a
      reporter gene containing the sequence in its promoter. This strategy was used to
      identify an essential protein that interacts in vivo with the yeast origin of DNA
      replication. Matches between its predicted amino acid sequence and peptide
      sequence obtained from the 50-kilodalton subunit of the yeast origin recognition
      complex (ORC) established that the gene isolated here, ORC6, encodes this
      subunit. These observations provide evidence that ORC recognizes yeast
      replication origins in vivo.

PMID- 8266076
TI  - Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL
      2 and IL-4.
AB  - The gamma chain of the interleukin-2 (IL-2) receptor is an indispensable subunit
      for IL-2 binding and intracellular signal transduction. A monoclonal antibody to
      the gamma chain, TUGm2, inhibited IL-2 binding to the functional IL-2 receptors
      and also inhibited IL-4-induced cell growth and the high-affinity binding of IL-4
      to the CTLL-2 mouse T cell line. Another monoclonal antibody, TUGm3, which
      reacted with the gamma chain cross-linked with IL-2, also immunoprecipitated the
      gamma chain when cross-linked with IL-4. These results suggest that the IL-2
      receptor gamma chain is functionally involved in the IL-4 receptor complex.

PMID- 8266077
TI  - Interleukin-2 receptor gamma chain: a functional component of the interleukin-7
      receptor.
AB  - The interleukin-2 receptor gamma chain (IL-2R gamma) is a necessary component of
      functional IL-2 receptors. IL-2R gamma mutations result in X-linked severe
      combined immunodeficiency (XSCID) in humans, a disease characterized by the
      presence of few or no T cells. In contrast, SCID patients with IL-2 deficiency
      and IL-2-deficient mice have normal numbers of T cells, suggesting that IL-2R
      gamma is part of more than one cytokine receptor. By using chemical cross
      linking, IL-2R gamma was shown to be physically associated with the IL-7
      receptor. The presence of IL-2R gamma augmented both IL-7 binding affinity and
      the efficiency of internalization of IL-7. These findings may help explain the
      defects of XSCID. Given its role in more than one cytokine receptor system, the
      common gamma chain (gamma c) is proposed as the designation for IL-2R gamma.

PMID- 8266078
TI  - Interleukin-2 receptor gamma chain: a functional component of the interleukin-4
      receptor.
AB  - The interleukin-2 (IL-2) receptor gamma chain (IL-2R gamma) is an essential
      component of high- and intermediate-affinity IL-2 receptors. IL-2R gamma was
      demonstrated to be a component of the IL-4 receptor on the basis of chemical
      cross-linking data, the ability of IL-2R gamma to augment IL-4 binding affinity,
      and the requirement for IL-2R gamma in IL-4-mediated phosphorylation of insulin
      receptor substrate-1. The observation that IL-2R gamma is a functional component
      of the IL-4 receptor, together with the finding that IL-2R gamma associates with
      the IL-7 receptor, begins to elucidate why deficiency of this common gamma chain
      (gamma c) has a profound effect on lymphoid function and development, as seen in
      X-linked severe combined immunodeficiency.

PMID- 8266079
TI  - Active oxygen species in the induction of plant systemic acquired resistance by
      salicylic acid.
AB  - A complementary DNA encoding a salicylic acid (SA)-binding protein has been
      cloned. Its properties suggest involvement in SA-mediated induction of systemic
      acquired resistance (SAR) in plants. The sequence of the protein is similar to
      that of catalases and the protein exhibits catalase activity. Salicylic acid
      specifically inhibited the catalase activity in vitro and induced an increase in
      H2O2 concentrations in vivo. H2O2 or compounds, such as SA, that inhibit
      catalases or enhance the generation of H2O2, induced expression of defense
      related genes associated with SAR. Thus, the action of SA in SAR is likely
      mediated by elevated amounts of H2O2.

PMID- 8266080
TI  - Functional requirement of a site-specific ribose methylation in ribosomal RNA.
AB  - The product of the PET56 nuclear gene of Saccharomyces cerevisiae was shown to be
      required for ribose methylation at a universally conserved nucleotide in the
      peptidyl transferase center of the mitochondrial large ribosomal RNA (21S rRNA).
      Cells reduced in this activity were deficient in formation of functional large
      subunits of the mitochondrial ribosome. The purified Pet56 protein catalyzed the
      site-specific formation of 2'-O-methylguanosine on in vitro transcripts of both
      mitochondrial 21S rRNA and Escherichia coli 23S rRNA. These results provide
      evidence for an essential modified nucleotide in rRNA.

PMID- 8266081
TI  - Inhibition of transcriptional regulator Yin-Yang-1 by association with c-Myc.
AB  - Yin-Yang-1 (YY1) regulates the transcription of many genes, including the
      oncogenes c-fos and c-myc. Depending on the context, YY1 acts as a
      transcriptional repressor, a transcriptional activator, or a transcriptional
      initiator. The yeast two-hybrid system was used to screen a human complementary
      DNA (cDNA) library for proteins that associate with YY1, and a c-myc cDNA was
      isolated. Affinity chromatography confirmed that YY1 associates with c-Myc but
      not with Max. In cotransfections, c-Myc inhibits both the repressor and the
      activator functions of YY1, which suggests that one way c-Myc acts is by
      modulating the activity of YY1.

PMID- 8266082
TI  - Separate GTP binding and GTPase activating domains of a G alpha subunit.
AB  - Most members of the guanosine triphosphatase (GTPase) superfamily hydrolyze
      guanosine triphosphate (GTP) quite slowly unless stimulated by a GTPase
      activating protein or GAP. The alpha subunits (G alpha) of the heterotrimeric G
      proteins hydrolyze GTP much more rapidly and contain an approximately 120-residue
      insert not found in other GTPases. Interactions between a G alpha insert domain
      and a G alpha GTP-binding core domain, both expressed as recombinant proteins,
      show that the insert acts biochemically as a GAP. The results suggest a general
      mechanism for GAP-dependent hydrolysis of GTP by other GTPases.

PMID- 8266084
TI  - Molecule of the year.

PMID- 8266083
TI  - Linearity of summation of synaptic potentials underlying direction selectivity in
      simple cells of the cat visual cortex.
AB  - Intracellular recordings from simple cells of the cat visual cortex were used to
      test linear models for the generation of selectivity for the direction of visual
      motion. Direction selectivity has been thought to arise in part from nonlinear
      processes, as suggested by previous experiments that were based on extracellular
      recordings of action potentials. In intracellular recordings, however, the
      fluctuations in membrane potential evoked by moving stimuli were accurately
      predicted by the linear summation of responses to stationary stimuli. Nonlinear
      mechanisms were not required.

PMID- 8266085
TI  - Bottleneck in human evolution and the Toba eruption.

PMID- 8266086
TI  - Getting organized to fight AIDS.

PMID- 8266087
TI  - East Europe: a chance to stop HIV.

PMID- 8266088
TI  - Draft genome map debuts on Internet.

PMID- 8266089
TI  - Scientists study 'cold war' fallout.

PMID- 8266090
TI  - Army targets a potential vaccine against cholesterol.

PMID- 8266091
TI  - Guides to the heart of the spliceosome.

PMID- 8266092
TI  - p53: at the crossroads of molecular carcinogenesis and risk assessment.

PMID- 8266093
TI  - Mutations in U6 snRNA that alter splice site specificity: implications for the
      active site.
AB  - What determines the precise sites of cleavage in the two transesterification
      reactions of messenger RNA (mRNA) splicing is a major unsolved question. Mutation
      of the invariant G (guanosine) at position 5 of 5' splice sites in Saccharomyces
      cerevisiae introns activates cleavage at nearby aberrant sites. A genetic
      approach was used to test the hypothesis that a base-pairing interaction between
      the 5' splice site and the invariant ACAGAG sequence of U6 is a determinant of 5'
      splice site choice. Mutations in U6 or the intron (or both) that were predicted
      to stabilize the interaction suppressed aberrant cleavage and increased normal
      cleavage. In addition, a mutation in the ACAGAG sequence suppressed mutations of
      the 3' splice site dinucleotide. These data can fit a model for the spliceosomal
      active site comprised of a set of RNA-RNA interactions between the intron, U2 and
      U6.

PMID- 8266094
TI  - The U5 and U6 small nuclear RNAs as active site components of the spliceosome.
AB  - Five small nuclear RNAs (U1, U2, U4, U5, and U6) participate in precursor
      messenger RNA (pre-mRNA) splicing. To probe their interactions within the active
      center of the mammalian spliceosome, substrates containing a single
      photoactivatable 4-thiouridine residue adjacent to either splice site were
      synthesized, and crosslinks were induced during the course of in vitro splicing.
      An invariant loop sequence in U5 small nuclear RNA contacts exon 1 before and
      after the first step of splicing because a crosslink between U5 and the last
      residue of exon 1 appeared in the pre-mRNA and then in the cutoff exon 1
      intermediate. Both of these crosslinked species could undergo subsequent
      splicing, indicating that the crosslinks reflect a functional interaction that is
      maintained through both reaction steps. The same U5 loop aligns the two exons for
      ligation since the first residue of exon 2 also became crosslinked to U5 in the
      lariat intermediate. An invariant sequence in U6 RNA became crosslinked to the
      conserved second position of the intron within both the lariat intermediate and
      the lariat intron product. On the basis of these results, several conformational
      arrangements of small nuclear RNAs within the spliceosomal active center can be
      distinguished, and additional mechanistic parallels between the spliceosome and
      self-splicing introns can be drawn.

PMID- 8266095
TI  - A mitochondrial protease with two catalytic subunits of nonoverlapping
      specificities.
AB  - The mitochondrial inner membrane protease is required for the maturation of
      mitochondrial proteins that are delivered to the intermembrane space. In the
      yeast Saccharomyces cerevisiae, this protease is now shown to be a complex that
      contains two catalytic subunits, Imp2p and the previously identified Imp1p.
      Primary structure similarity indicates that Imp1p and Imp2p are related to each
      other and to the family of eubacterial and eukaryotic signal peptidases. Imp1p
      and Imp2p have separate, nonoverlapping substrate specificities. In addition to
      its catalyzing the cleavage of intermembrane space sorting signals, Imp2p is
      required for the stable and functional expression of Imp1p. Thus, inner membrane
      protease, and by analogy eukaryotic multisubunit signal peptidases, may have
      acquired multiple catalytic subunits by gene duplication to broaden their range
      of substrate specificity.

PMID- 8266096
TI  - Generation of impossible cross-peaks between bulk water and biomolecules in
      solution NMR.
AB  - Intermolecular multiple-quantum coherences between bulk water and a glycoprotein
      fragment at modest concentration (20 mM) have been experimentally produced and
      detected, although such coherences are inconceivable in the normal theoretical
      framework of nuclear magnetic resonance. A density matrix treatment explains
      these results by including the long-range dipolar interaction between spins and
      by discarding the high-temperature approximation. These results imply that peak
      intensities (critical for structural determinations) can be distorted in many
      gradient experiments, and show that magic-angle gradients provide substantial
      improvements with reduced gradient strengths. They also suggest methods for
      contrast enhancement in magnetic resonance imaging.

PMID- 8266097
TI  - Crystal structure of the repetitive segments of spectrin.
AB  - The elongated proteins of the spectrin family (dystrophin, alpha-actinin, and
      spectrin) contain tandemly repeated segments and form resilient cellular
      meshworks by cross-linking actin filaments. The structure of one of the
      repetitive segments of alpha-spectrin was determined at a 1.8 angstrom
      resolution. A segment consists of a three-helix bundle. A model of the interface
      between two tandem segments suggests that hydrophobic interactions between
      segments may constrain intersegment flexibility. The helix side chain
      interactions explain how mutations that are known to produce hemolytic anemias
      disrupt spectrin associations that sustain the integrity of the erythrocyte
      membrane.

PMID- 8266098
TI  - A covalent enzyme-substrate intermediate with saccharide distortion in a mutant
      T4 lysozyme.
AB  - The glycosyl-enzyme intermediate in lysozyme action has long been considered to
      be an oxocarbonium ion, although precedent from other glycosidases and
      theoretical considerations suggest it should be a covalent enzyme-substrate
      adduct. The mutation of threonine 26 to glutamic acid in the active site cleft of
      phage T4 lysozyme (T4L) produced an enzyme that cleaved the cell wall of
      Escherichia coli but left the product covalently bound to the enzyme. The
      crystalline complex was nonisomorphous with wild-type T4L, and analysis of its
      structure showed a covalent linkage between the product and the newly introduced
      glutamic acid 26. The covalently linked sugar ring was substantially distorted,
      suggesting that distortion of the substrate toward the transition state is
      important for catalysis, as originally proposed by Phillips. It is also
      postulated that the adduct formed by the mutant is an intermediate, consistent
      with a double displacement mechanism of action in which the glycosidic linkage is
      cleaved with retention of configuration as originally proposed by Koshland. The
      peptide part of the cell wall fragment displays extensive hydrogen-bonding
      interactions with the carboxyl-terminal domain of the enzyme, consistent with
      previous studies of mutations in T4L.

PMID- 8266099
TI  - Chromosome condensation in Xenopus mitotic extracts without histone H1.
AB  - The contribution of histone H1 to mitotic chromosome condensation was examined
      with the use of a cell-free extract from Xenopus eggs, which transforms condensed
      sperm nuclei into metaphase chromosomes. When H1 was removed from the extract,
      the resultant metaphase chromosomes were indistinguishable from those formed in
      complete extract. Nucleosomal spacing was the same for both. Thus, H1 is not
      required for the structural reorganization that leads to condensed metaphase
      chromosomes in this egg extract.

PMID- 8266100
TI  - Involvement of U6 snRNA in 5' splice site selection.
AB  - Two models describing the interaction between U6 small nuclear RNA (snRNA) and
      the 5' splice site of introns have been proposed on the basis of cross-linking
      experiments. Here it is shown that a conserved sequence present in U6 snRNA forms
      base pairs with conserved nucleotides at the 5' splice junction and that this
      interaction is involved in 5' splice site choice. These results demonstrate a
      specific function for U6 snRNA in splicing and suggest that U6 snRNA has a
      proofreading role during splice site selection. A model is presented in which
      this new interaction, in concert with previously described interactions between
      U6 snRNA, U2 snRNA, and the pre-messenger RNA, would position the branch point
      near the 5' splice site for the catalysis of the first splicing step.

PMID- 8266101
TI  - Connexin mutations in X-linked Charcot-Marie-Tooth disease.
AB  - X-linked Charcot-Marie-Tooth disease (CMTX) is a form of hereditary neuropathy
      with demyelination. Recently, this disorder was mapped to chromosome Xq13.1. The
      gene for the gap junction protein connexin32 is located in the same chromosomal
      segment, which led to its consideration as a candidate gene for CMTX. With the
      use of Northern (RNA) blot and immunohistochemistry technique, it was found that
      connexin32 is normally expressed in myelinated peripheral nerve. Direct
      sequencing of the connexin32 gene showed seven different mutations in affected
      persons from eight CMTX families. These findings, a demonstration of inherited
      defects in a gap junction protein, suggest that connexin32 plays an important
      role in peripheral nerve.

PMID- 8266102
TI  - Perceptual organization and the judgment of brightness.
AB  - The perceived brightness of a gray patch depends on the surrounding context. For
      example, a medium-gray patch appears darker when placed on a bright background
      and brighter when placed on a dark background. Models to explain these effects
      are usually based on simple low-level mechanisms. A new set of brightness
      illusions cannot be explained by such models. In these illusions, the brightness
      percept is strongly influenced by the perceptual organization of the stimuli.
      Simple modifications of the stimuli that should have little effect on low-level
      mechanisms greatly alter the strength of the illusion. These effects may be
      ascribed to more complex mechanisms occurring later in the visual system.

PMID- 8266103
TI  - Distinct roles for cyclin-dependent kinases in cell cycle control.
AB  - The key cell-cycle regulator Cdc2 belongs to a family of cyclin-dependent kinases
      in higher eukaryotes. Dominant-negative mutations were used to address the
      requirement for kinases of this family in progression through the human cell
      cycle. A dominant-negative Cdc2 mutant arrested cells at the G2 to M phase
      transition, whereas mutants of the cyclin-dependent kinases Cdk2 and Cdk3 caused
      a G1 block. The mutant phenotypes were specifically rescued by the corresponding
      wild-type kinases. These data reveal that Cdk3, in addition to Cdc2 and Cdk2,
      executes a distinct and essential function in the mammalian cell cycle.

PMID- 8266104
TI  - Receptive field reorganization in dorsal column nuclei during temporary
      denervation.
AB  - Altered sensory input can result in the reorganization of somatosensory maps in
      the cerebral cortex and thalamus, but the extent to which reorganization occurs
      at lower levels of the somatosensory system is unknown. In cat dorsal column
      nuclei (DCN), the injection of local anesthetic into the receptive fields of DCN
      neurons resulted in the emergence of a new receptive field in all 13 neurons
      studied. New receptive fields emerged rapidly (within minutes), sometimes
      accompanied by changes in adaptation rates and stimulus selectivity, suggesting
      that the new fields arose from the unmasking of previously ineffective inputs.
      Receptive field reorganization was not imposed by descending cortical inputs to
      the DCN, because comparable results were obtained in 10 additional cells when the
      somatosensory and motor cortex were removed before recording. These results
      suggest that mechanisms underlying somatotopic reorganization exist at the
      earliest stages of somatosensory processing. Such mechanisms may participate in
      adaptive responses of the nervous system to injury or continuously changing
      sensory stimulation.

PMID- 8266105
TI  - WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing
      variant.
AB  - A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor
      activity of WT1, a zinc finger transcription factor that is expressed in the
      developing human kidney and is mutationally inactivated in a subset of Wilms
      tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth
      of RM1 cells. The endogenous WT1 transcript in these cells was devoid of exon 2
      sequences, a splicing alteration that was also detected in varying amounts in all
      Wilms tumors tested but not in normal kidney. Production of this abnormal
      transcript, which encodes a functionally altered protein, may represent a
      distinct mechanism for inactivating WT1 in Wilms tumors.

PMID- 8266106
TI  - Peptide translocation by variants of the transporter associated with antigen
      processing.
AB  - Major histocompatibility complex (MHC) class I molecules associate with peptides
      that are delivered from the cytosol to the lumen of the endoplasmic reticulum by
      the transporter associated with antigen processing (TAP). Liver microsomes of SHR
      and Lewis rats, which express different alleles of TAP (cim(b) and cim(a),
      respectively), accumulate different sets of peptides. Use of MHC congenic rats
      assigned this difference to the MHC, independent of the class I products
      expressed. Both the cim(a) and cim(b) TAP complexes translocate peptides with a
      hydrophobic carboxyl terminus, but translocation of peptides with a carboxyl
      terminal His, Lys, or Arg residue is unique to cim(a). Thus, the specificity of
      the TAP peptide translocator restricts the peptides available for antigen
      presentation.

PMID- 8266107
TI  - Male sexual orientation and genetic evidence.

PMID- 8266108
TI  - Toxic oil syndrome and eosinophilia-myalgia syndrome: May 8-10, 1991, World
      Health Organization meeting report.
AB  - In May 1991, researchers and clinicians from throughout the world met at a
      workshop sponsored by the Regional Office for Europe of the World Health
      Organization in collaboration with the Fondo de Investigacion Sanitaria, Spain,
      and the U.S. Food and Drug Administration, National Institutes of Health,
      National Institutes of Mental Health, and Centers for Disease Control and
      Prevention to share information about two very similar diseases--toxic oil
      syndrome and eosinophilia-myalgia syndrome. In this paper the interpretation of
      conference proceedings is presented, current knowledge of the two disorders is
      summarized, and some possible areas for future research are mentioned. Toxic oil
      syndrome and eosinophilia-myalgia syndrome have many similarities. Both are
      related to consumer products that were presumed to be safe but have been found to
      have numerous trace contaminants, many of which remain to be identified,
      including the etiologic agents of both disorders. Both illnesses affect patients
      clinically by causing intense, incapacitating myalgias and a marked peripheral
      eosinophilia. Other rheumatologic manifestations are common in both, including
      arthralgias, sicca syndrome, scleroderma-like skin changes, carpal tunnel
      syndrome, and joint contractures. No clinical or laboratory feature has been
      found to be pathognomonic of either disease, and accurate diagnosis rests on the
      clinical judgment of the attending physician. Deaths have occurred in both
      diseases, and the cumulative mortality for each is approximately 2.5% for the
      first 2 years. Long-term complications include pulmonary hypertension, peripheral
      neuropathies, and joint contractures. Although treatment with corticosteroids has
      resulted in significant symptomatic relief in persons with either disorder, it
      does not alter the clinical course or long-term outcome. Research into the
      etiologic agents, preferred treatments, and ways to avoid similar problems in the
      future is needed.

PMID- 8266109
TI  - Indications for upper extremity surgery in rheumatoid arthritis patients.
AB  - In selected circumstances, especially those associated with pain and mechanical
      instability, early surgical therapy is indicated for patients with rheumatoid
      arthritis. Close consultation between the rheumatologist and surgeon enables
      identification of focused goals attainable by synovectomy, ligament or tendon
      reconstruction, joint replacement, or arthrodesis. If these goals are met, the
      result can be a gratifying return of function and independence. This article
      describes some of the more common deformities of the hand, wrist, and elbow in
      patients with rheumatoid arthritis. Current surgical therapy, along with outcome
      and complications, is also discussed. Emphasis is placed on decisions and
      indications for surgical evaluation.

PMID- 8266111
TI  - Synovial fluid lipoproteins: review of current concepts and new directions.
AB  - Recent developments in plasma lipoprotein and apolipoprotein research have been
      striking, but few studies have focused on the analysis of lipoproteins in
      synovial fluid (SF). SF contains small amounts of lipoproteins and
      apolipoproteins. The lipid concentration of normal human SF is extremely low and
      is in sharp contrast to the concentrations found in plasma. Little is known about
      the lipids in pathological SF, but studies have noted increased cholesterol and
      lipoprotein content in rheumatoid arthritis (RA) SF ranging from 40% to 60% of
      the total plasma lipoproteins. Recently apolipoproteins AI, B and E have also
      been found to be in increased amounts in RA SF. Several theories have been
      proposed to account for the increased presence of SF lipids in RA. Animal and
      human studies indicate the SF cholesterol, lipoproteins, and apolipoproteins may
      aggravate the inflammatory reaction within the synovial space. Research suggests
      an immunologic role for plasma lipoproteins on lymphocyte and monocytes in the
      blood and lymph. SF lipoproteins and apolipoproteins should be studied to define
      their actions within the synovial space.

PMID- 8266110
TI  - The pathogenesis and prognosis of lupus nephritis: information from repeat renal
      biopsy.
AB  - Of an inception cohort of 87 patients with lupus nephritis who underwent a renal
      biopsy, 42 underwent second biopsies a median of 25 months later. From first to
      second biopsy, focal and diffuse proliferative nephritis (World Health
      Organization classes III and IV) became less frequent, and mesangial
      hypercellularity (class II) and a membranous pattern (class V) increased. The
      National Institutes of Health activity index and mesangial and subendothelial
      deposits declined while the chronicity index, a tubulointerstitial index, and
      subepithelial deposits increased. The biopsy improvement in urinary protein
      excretion was best explained by decreases in the activity index score and the
      amount of subendothelial deposits. A decrease in the amount of subendothelial
      deposits tended to predict an improvement in the serum creatinine level from
      first to second biopsy. With follow-up from second biopsy in excess of 7 years,
      the best predictors of long-term outcome were the ultrastructural variables
      mesangial, subendothelial and subepithelial deposits. When the change in biopsy
      predictors from first to second biopsy was evaluated, a decrease in the amount of
      mesangial or subendothelial deposits was best at predicting a lower risk of renal
      impairment, renal insufficiency, and mortality. The results confirm the
      importance of immune complex deposition as measured by electron microscopy in the
      pathogenesis of lupus nephritis and suggest that control of this process may
      alter renal function and prognosis.

PMID- 8266112
TI  - Rheumatic manifestations of hyperlipidemia and antihyperlipidemia drug therapy.
AB  - Conflicting data exist with respect to the existence and clinical manifestations
      of a hyperlipidemic arthropathy. Reasonable evidence supports the existence of a
      migratory polyarthritis similar to rheumatic fever in patients homozygous for
      type II hyperlipidemia. Although similar complaints have been described in
      patients heterozygous for this condition, findings have been inconsistent among
      various reports. It is possible that high lipid levels are required to induce
      rheumatic complaints, and these are found predominantly in homozygous patients.
      Even so, rheumatic syndromes appear to be more attributable to periarthritis
      because evidence of inflammatory arthritis is largely lacking. In contrast,
      Achilles tendinitis appears to be associated with heterozygous type II
      hyperlipidemia and presumably is based on lipid deposits within the tendon. Gout
      is an accepted association of type IV hyperlipidemia. In addition, oligoarticular
      symptoms have been described with type IV hyperlipidemia. However, no consistent
      clinical entity has emerged. Drugs used in the treatment of hyperlipidemia are
      associated with a variety of rheumatic problems, including proximal myopathy and
      lupus-like syndromes. The most commonly implicated drugs are the
      hydroxymethylglutaryl-coenzyme A reductase inhibitors and the fibric acid
      derivatives.

PMID- 8266113
TI  - Cholesterol crystals in synovial and bursal fluid.
AB  - Cholesterol crystals were found in two patients with classic rheumatoid arthritis
      (RA). In one patient, cholesterol crystals were found in synovial fluid from both
      shoulder joints, and in the second they were in an olecranon bursa. To examine
      the possible systemic etiology of cholesterol crystals in synovial and bursal
      fluid, lipid concentrations and the presence of serum antilipoprotein antibodies
      were measured. Antilipoprotein antibodies were not found. The concentration of
      lipid and lipoproteins, as well as the normal pattern of lipoprotein on agarose
      gel, eliminates the possibility of hyperlipoproteinemia. Results seemed to
      exclude a systemic etiology for the formation of cholesterol crystals in synovial
      and bursal fluid in the RA patients. It appears that several local factors such
      as defective drainage, local destruction, increased permeability of synovial
      membrane, and intraarticular (bursal) bleeding are possible etiologies.

PMID- 8266114
TI  - Clinical expression and laboratory detection of red blood cell membrane protein
      mutations.

PMID- 8266115
TI  - Increasing incidence of non-Hodgkin's lymphoma.

PMID- 8266116
TI  - Molecular aspects of chromosomal translocation t(14;18).

PMID- 8266117
TI  - Introduction: replacement therapy for hemophilia: impact on the immune system.

PMID- 8266119
TI  - Abstracts restructured.

PMID- 8266118
TI  - The treatment of hemophilia--a double-edged sword.

PMID- 8266120
TI  - Diving (underwater) for pulmonary pearls.

PMID- 8266121
TI  - A review of cases of pulmonary barotrauma from diving.
AB  - Pulmonary barotrauma is a condition where lung injury arises from excessive
      pressure changes. Five cases of pulmonary barotrauma from diving have been seen
      at the Naval Medicine and Research Centre from 1970 to 1991. Four suffered
      surgical emphysema while one developed cerebral arterial gas embolism (CAGE).
      These cases are presented and discussed, including the predisposing factors,
      common signs and symptoms and essential treatment of this condition.

PMID- 8266122
TI  - Condom knowledge, attitudes and use among patients attending the public STD
      clinic in Singapore.
AB  - Three hundred patients (255 males and 45 females) attending the public STD clinic
      in Singapore were interviewed regarding their frequency of condom use, attitudes
      towards condoms, problems related to condom use and places of purchase of the
      condoms. Among respondents with regular partners, 55.2% of males and 48.8% of
      females never used condoms, only 12.4% of males and 16.3% of females used condoms
      consistently. Among respondents with non-regular partners, only 2.2% of males
      used condoms consistently. The commonest reasons why male respondents did not use
      condoms consistently were that condoms decreased sensation, condoms made sex
      mechanical, the use of other forms of contraception, no condoms were available,
      and the perception that there was no risk of contracting STD/AIDS. Condoms were
      most commonly obtained from sex partners, supermarkets, roadside sundry shops and
      the Maternal & Child Health Clinics (MCHCs). About 8% of both males and females
      had experienced some problems with condoms before. Greater efforts to promote the
      practice of protected intercourse among the STD patient population as well as in
      the general population are required in order to control the spread of STD and
      AIDS in Singapore.

PMID- 8266123
TI  - Dementia in elderly Malays--preliminary findings of a community survey.
AB  - This is a study of the prevalence of dementia in elderly Malays living in the
      Eunos district of Singapore. The subjects included all Malays 65 years and more
      living in public housing, and they were first interviewed and screened for any
      cognitive deficit using the Malay version of the Elderly Cognitive Assessment
      Questionnaire (ECAQ). All those who scored 5 or less in the ECAQ were assessed
      again with a more detailed questionnaire called the Geriatric Mental State (GMS)
      schedule. This is the preliminary results of 149 subjects interviewed--77 men and
      72 women. Data from the GMS were analysed by a computer diagnostic programme,
      AGECAT. There were only 6 cases of dementia and the overall prevalence of
      dementia in the sample was estimated as 4.0%. In the age group 65 to 74 years the
      rate was 2.5% and this increased to 10.3% in those 75 years and more. The
      prevalence of dementia in elderly Malays is higher than elderly Chinese in
      Singapore, but it is similar to the results of studies in New York and Liverpool.
      All the subjects with dementia were living with their families and they had good
      social resources.

PMID- 8266124
TI  - Race, culture and Myopia in 110,236 young Singaporean males.
AB  - Computerised data of 110,236 Singaporean males aged 15 to 25 (mean 17.75) years
      who underwent compulsory medical examination from April 1987 to January 1992 was
      used to estimate the prevalence of myopia among young Chinese, Malay, Indian and
      Eurasian Singaporean males. The prevalence of myopia amongst the different racial
      groups was compared after they had been matched for important known confounding
      factors such as age, sex, educational attainment and degree of urbanization of
      place of residence. The estimated myopia prevalence was 48.5% in Chinese, 34.7%
      in Eurasians, 30.4% in Indians and 24.5% in Malays. The overall myopia prevalence
      rate for all races combined was 44.2%. Within each educational group, the Chinese
      generally had the highest myopia prevalence whilst the Malays generally had the
      lowest. Myopia prevalence among the Indians tended to be between that of the
      Chinese and the Malays. Having matched the various racial groups for age, sex,
      educational attainment and degree of residential urbanization, it would appear
      that racial and cultural differences are major influences responsible for the
      difference in myopia prevalence observed amongst the different races.

PMID- 8266125
TI  - Shiftwork in Singapore.
AB  - In 1985, over 94,000 persons were engaged in shiftwork. With the continued
      emphasis on capital-intensive industries and growing demand for "round-the-clock"
      services, shiftwork is increasingly becoming an economic necessity in many
      industries in Singapore. A survey in 1991 confirmed this trend. The study covered
      4,996 private sector establishments employing 25 or more paid employees. 34.4% of
      the establishments had shiftworkers. In terms of employees, 32% or 206,965
      employees were working shifts. While the 8-hour shift schedule was still the
      predominant pattern, there was a ten-fold increase in the number of 12-hour
      shiftworkers. A trend towards permanent shift schedules was also noted. It was
      interesting that the proportion of shiftworkers doing nightwork decreased to
      36.9% from 45.1% in 1985. The health implications of shiftwork have been widely
      reported. So far, our own studies indicate no serious long-term health effects
      among shiftworkers. However, further studies are needed to determine if
      preventive measures can be taken to minimise the common complaints of sleep
      problems and tiredness, particularly among rotating shiftworkers.

PMID- 8266126
TI  - Psychiatric illness in Filipino maids admitted to Woodbridge Hospital.
AB  - This is a retrospective and descriptive study of 44 Filipino maids who had a
      psychiatric illness in Singapore and were admitted to the state psychiatric
      hospital. Of those with psychosis, one quarter was diagnosed to have a Brief
      Reactive Psychosis, 2 had a Depressive illness, whilst 3 had a Schizophrenic
      illness. One-fifth had symptoms of an Atypical Psychosis. The onset of illness
      occurred at the sixth week of stay in Singapore, in the majority of the group.
      Psychosocial and social-cultural factors were considered as causative to the
      failure of adaptation resulting in a breakdown of coping mechanisms leading to
      the illness. Educational and marital status, and lack of integration with the new
      environment are some of the factors discussed. Life events occurring before the
      onset of illness were mainly financial and relationship difficulties. Two
      experienced deaths in their families at home. Auditory hallucinations, present in
      twenty-six of the group, and delusions, present in sixteen, were the main
      symptomatology discussed. The delusions had mainly sexual and religious themes.
      Seven had a history of suicidal attempts.

PMID- 8266127
TI  - Acute physiology and chronic health evaluation (APACHE II) scoring in the Medical
      Intensive Care Unit, National University Hospital, Singapore.
AB  - The intensive care unit provides multisystem support and therapy to critically
      ill patients, and represents an expensive part of hospital medicine. This survey
      validates the use of APACHE II as a severity scoring system that allows reliable
      prediction of outcome of intensive care patients in Singapore. The mortality rate
      of 37.4% in our medical intensive care unit compares favourably with the other
      established intensive care units in the United States of America. Our results
      also indicate that the aged fared as well as their younger counterparts. Patients
      with sepsis fared poorer than expected from their APACHE II scores, and stroke
      patients needing intensive care admission had an extremely poor prognosis
      (mortality rate of 85.7%). High APACHE II scores are associated with invasive
      haemodynamic monitoring.

PMID- 8266128
TI  - Speech disorders in closed head injury patients.
AB  - Head injuries vary in type and degree of severity and clinicians agree that most
      individuals who suffer head injury have cognitive, speech injury, behavioural and
      sensory motor problems immediately after and during their rehabilitative phase.
      METHOD: The hospital courses of thirty-one closed head injury (CHI) patients
      admitted to our Rehabilitation Department from January 1990 to April 1991 were
      studied with particular reference to their speech disorders. RESULTS: Severity of
      the initial brain injury, best measured by length of coma using the Glasgow Coma
      Scale (GCS) was the most significant predictor of outcome, defined by the Glasgow
      Outcome Scale (GOS). Eighty-one percent of our patients were unconscious
      immediately following their injury. Upon admission into our neurosurgical
      department, thirty-nine percent were comatose with a Glasgow Coma Scale score of
      eight or less. Fifty-two percent had a score of twelve or more and the rest were
      in between. Twenty-six percent had skull fractures, while seventy-four percent
      had one or more extracranial injuries. Neurologically eighty-one percent of our
      patients had either a left or right hemiplegia/paresis. In the assessment of
      speech, thirty percent were aphasic, twenty-five percent had motor speech
      disorders, thirty-two percent had mixed speech deficits and thirteen percent did
      not have any significant speech problems. Average stay in the Rehabilitation
      Department was ten weeks. CONCLUSION: Although most patients showed an overall
      trend of speech improvement across time, the severely injured (Glasgow Coma Scale
      less than eight) continued to manifest permanent residual deficits especially
      those with expressive, mixed or global aphasia. The mild to moderately injured
      (Glasgow Coma Scale more than eight) seem to have anomia and word retrieval
      difficulty with little receptive language impairment, and these persisted months
      after discharge.

PMID- 8266129
TI  - The ratios of area of foot print to area of foot outline and diabetic sole ulcer
      formation.
AB  - The ratio of area of foot print to area of foot outline for each foot was studied
      in 50 normal and 70 diabetic subjects. The diabetic group was divided into 2
      groups: 44 patients without and 26 patients with sole ulcers. The chief aim was
      to find a ratio that could predict ulcer formation. One hundred feet in the
      normal subjects had a mean ratio of 0.621 with a range of 0.51-0.72. The 88 non
      ulcerated feet in the diabetic patients had a mean ratio of 0.611 with a range of
      0.49-0.70. The difference was statistically not significant (p > 0.05). Thirty
      two ulcerated feet in the 26 diabetic patients had a mean ratio of 0.580 with a
      range of 0.47-0.68. The difference between the ulcer and the non-ulcer group was
      statistically significant (p < 0.01). Twenty non-ulcerated feet in 20 diabetic
      patients with unilateral involvement had a mean ratio of 0.60 with a range of
      0.50-0.69. The difference between the ulcerated and non ulcerated feet in these
      20 unilateral involved patients was also statistically significant (p < 0.01).
      The sole ulcers in our study were distributed mainly beneath the metatarsal heads
      and calcaneum. Analysis of the foot prints revealed multiple dark print areas.
      They were at the locations corresponding to the above bony prominences. As these
      bony prominences were high pressure points, the dark print areas could serve as
      crude indicators of excessive pressure. The diabetic ulcer group had smaller mean
      ratio and the reduction of the contact area could contribute to the formation of
      sole ulcers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266130
TI  - Reliability of computerised electrocardiographic reports.
AB  - The aim of this study is to assess the reliability of computerised reporting of
      electrocardiograms (ECG). Fifty ECG performed consecutively at the outpatient
      department of the Penang Adventist Hospital on the Marquette 12SL-SC were
      studied. Two physicians independently reviewed the ECG and the manual readings
      were compared with each other and to the computer reports. There was no
      significant difference in the measurement of rate. The PR and QT intervals
      measured by the two physicians were similar but each was significantly different
      from the computer reading. The QRS duration assessed by Physician 1 was similar
      to the computer reading but each was significantly different from that of
      Physician 2. The overall diagnosis was the same between the two physicians in
      76%, between Physician 1 and the computer in 68%, and between Physician 2 and the
      computer in 78%. No ECG was reported as normal by the computer and said to be
      abnormal by either physician. Thus, the computer programme is reasonably reliable
      in ECG reporting with computer-physician variability being comparable to inter
      physician variability.

PMID- 8266131
TI  - Fibreoptic bronchoscopy in the diagnosis of pulmonary tuberculosis--a Malaysian
      experience.
AB  - We report our experience on the use of fibreoptic bronchoscopy in the diagnosis
      of pulmonary tuberculosis. The case records of 1,274 patients who underwent
      fibreoptic bronchoscopy at the National Tuberculosis Centre, Kuala Lumpur,
      Malaysia during a three-year period were reviewed. In 120 of them the final
      diagnosis was tuberculosis. Bronchoscopy confirmed the diagnosis in 37 patients
      (30.8%). This was achieved by bronchial aspiration for culture in 26 patients
      (70.3%) and bronchial biopsy for histopathology in 11 patients (29.7%). It was
      the exclusive method of confirmation in 16 patients (13.3%). Sputum culture was
      positive in 62 patients (51.7%) including 41 patients (34.2%) in whom
      bronchoscopy was unhelpful. Six patients had diagnosis confirmed by other means
      while in 36 others (30%) it was based on clinical features and supportive basic
      investigations. There were no complications noted. We conclude that while sputum
      examination remains the mainstay for diagnosing pulmonary tuberculosis,
      fibreoptic bronchoscopy serves as a safe and useful adjunct.

PMID- 8266132
TI  - Effect of intraperitoneal administration of zinc in C57/6J mice.
AB  - Intraperitoneal administration of zinc chloride to C57/6J mice in vivo at 28
      micrograms/g body weight was more lethal to the male mice and induced growth
      retardation in the male and female survivors. In the group of experimental
      survivors, the weight of the lungs were significantly decreased compared with the
      control animals. The inherent dangers of zinc excess is highlighted, especially
      with regard to the possibility of cumulative zinc toxicity.

PMID- 8266133
TI  - Acute hemiparesis with hemichorea and crossed hemiparesis; unusual presentation
      for myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disease mediated by antibodies directed
      against the acetylcholine receptor. Patients typically present with weakness and
      fatiguability involving predominantly ocular and bulbar muscles. We describe 2
      patients with acute weakness, one with a left hemiparetic pattern and chorea, and
      the other with crossed left hemiparesis and right facial weakness. More typical
      features of generalised myasthenia developed with time and both had thymic
      follicular hyperplasia on thymic histopathology. Clinical improvement occurred in
      both following thymectomy and immunosuppression. These cases exemplify the fact
      that markedly asymmetric limb weakness can be an early feature of generalised
      myasthenia gravis.

PMID- 8266134
TI  - Delivery after a lower segment caesarean section.
AB  - A retrospective study on the outcome of 130 consecutive patients with a previous
      lower segment Caesarean section who delivered in Kandang Kerbau Hospital,
      Singapore from January to June 1989 was performed. Seventy-six percent of these
      patients were selected for a trial of labour and 24% of the patients had a repeat
      (elective) Caesarean section. Vaginal delivery was achieved in 65% of patients
      chosen to undergo a trial of labour. A trial of labour was found to be relatively
      safe with only a 0.7% incidence of uterine dehiscence and a perinatal mortality
      of 10.1 per 1,000 births with no maternal mortality. Cephalopelvic disproportion
      in the previous pregnancy and cervical dilatation during the previous Caesarean
      section were not important prognostic factor for the subsequent pregnancy
      outcome. A previous vaginal delivery in patients who had a previous Caesarean
      section was a good prognostic factor for a subsequent successful vaginal delivery
      (p < 0.05) in the trial of labour. More vaginal deliveries (p < 0.05) were
      achieved when oxytocic infusion was used in selected cases during the trial of
      labour. Maternal morbidities were higher in patients who had a failed trial of
      labour (57%) and repeat elective Caesarean section (20%) than those who had a
      successful trial of labout (10%). Management of patients with a previous lower
      segment Caesarean section may present a dilemma, but if properly conducted, the
      outcome can be favourable.

PMID- 8266135
TI  - The Mental Diseases Hospital, Singapore (1st 100 years)--Part IV.
AB  - This article (in four parts) traces the history of the first four Mental
      Hospitals built in Singapore, which were occupied in 1840, 1861, 1887 and 1928.
      The management of the patients is described; also their lives and deaths. Mention
      is also made of the doctors and others who looked after them.

PMID- 8266136
TI  - Factors affecting responses of infants with respiratory distress syndrome to
      exogenous surfactant therapy.
AB  - Approximately 20% to 30% of infants with respiratory distress syndrome (RDS) do
      not respond to surfactant replacement therapy. Unfortunately there is no uniform
      definition of 'response' or 'non-response' to surfactant therapy. Response was
      based on improvement in a/A PO2 and/or mean airway pressure (MAP) by some and on
      improvement in FIO2 and/or MAP by others. Even the point of time at which
      evaluation of response was done is different in various reports. There is an
      urgent need to adopt an uniform definition. Most premature babies are surfactant
      deficient which is the aetiological factor of RDS. Generally good antenatal care
      and perinatal management are essential in avoidance of premature birth. Babies
      with lung hypoplasia and who are extremely premature (less than 24 weeks of
      gestation) do not respond well to exogenous surfactant replacement because of
      structural immaturity. Prompt management of asphyxiated birth and shock are
      necessary as there may be negative response to surfactant replacement. Foetal
      exposure to glucocorticoids improves responsiveness to postnatal administration
      of surfactant. Antenatal steroid therapy has become an important part of
      management of RDS with surfactant replacement. The premature lungs with high
      alveolar permeability tend to develop pulmonary oedema. With the presence of
      plasma-derived surfactant inhibitors, the response to exogenous surfactant may be
      affected. These inhibitors may also be released following ventilator barotrauma.
      The standard of neonatal intensive care such as ventilatory techniques has an
      important bearing on the outcome of the RDS babies.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8266137
TI  - The hypochondriacal patient.
AB  - Until recently, hypochondriasis received relatively little attention from
      clinical investigators. The epidemiology is largely unknown. The numerous
      theories on the aetiology cannot explain the psychopathology. Recent interest and
      attempts at operationally defining the syndrome have resulted in some progress in
      the recognition and treatment of the hypochondriacal patient. The physician's
      reaction is highlighted as an important factor that contributes to the initiation
      and maintenance of this difficult condition.

PMID- 8266138
TI  - An unusual cause of giddiness. Fig. 1: Complete heart block with prolonged QT
      interval. Fig. 2: Torsades de pointes.

PMID- 8266139
TI  - An unusual cause for cyanosis.
AB  - Cyanosis is a common physical sign in clinical medicine. Cardiac or respiratory
      conditions are the usual causes. We report a patient with an unusual cause for
      cyanosis and highlight the salient clues that lead to the diagnosis.

PMID- 8266140
TI  - Neonatal melioidosis.
AB  - We report a neonate with melioidosis. The presentation, progress and treatment
      are described, followed by a discussion on melioidosis.

PMID- 8266141
TI  - Urinary incontinence caused by prazosin.

PMID- 8266142
TI  - On remunerating doctors.

PMID- 8266143
TI  - Febrile transfusion reaction: what to do next?

PMID- 8266144
TI  - Psychological impact of breast cancer.

PMID- 8266145
TI  - A prospective study on the use of leucocyte-filters in reducing blood transfusion
      reactions in multi-transfused thalassemic children.
AB  - Two hundred and eleven blood transfusions were administered to 26 multi
      transfused thalassemic children (aged 9 months-13 years) over a 6-month period.
      Eighteen children were receiving buffy coat-poor packed red cells (PRC) prepared
      by centrifuge while 8 children received filtered blood through a leucocyte-filter
      (Sepacell R-500A). Transfusion reactions occurred in 8.5% (n = 18) of
      transfusions and in 42.3% (n = 11) of patients. 11.9% (n = 16) and 2.6% (n = 2)
      of reactions occurred in 50% (n = 9) and 25% (n = 2) of patients receiving buffy
      coat-poor PRC and filtered blood respectively. Transfusion reactions in toto were
      significantly reduced in the group receiving filtered blood (p < 0.05). However,
      febrile reaction alone was not significantly reduced (p > 0.1). The median onset
      and duration of reaction were 2 hours (range 10 minutes-18 hours) and 4 hours
      (range 1/2-24 hours) respectively. 72.2% (n = 13) of the reactions occurred
      occurred during transfusion. 88.8% (n = 16) of the reactions caused only one
      symptom. 19.2% (n = 5) of all patients had recurrent reactions, all of them
      receiving buffy coat-poor PRC. The commonest clinical manifestation was fever (n
      = 7), followed by urticaria (n = 5) and petechial rash (n = 2). The outcome was
      good, with no patient experiencing symptoms exceeding 24 hours. Only 0.9% (n = 2)
      of the transfusions were discontinued.

PMID- 8266146
TI  - Psychological aspects of breast cancer: implications for practice in Singapore.
AB  - The purpose of this paper is two-fold. It begins with a brief review of the
      relationship between psychology and health, and the theoretical rationale for
      different approaches in counselling. The psychological aspects of breast cancer
      are then described with reference to three different treatment stages, and
      recommendations are made about informal counselling for patients.

PMID- 8266147
TI  - Percutaneous transseptal balloon mitral valvotomy: initial experience in
      Singapore.
AB  - Between June 1990 and August 1991, 28 percutaneous transseptal balloon mitral
      valvotomy procedures were attempted in 27 patients (23 women and 4 men; mean age
      39.8 +/- 9.3 years) with severe mitral stenosis. Successful mitral valvotomy was
      achieved in 25 patients (primary success rate of 92%). Mitral valve area
      increased from 0.82 +/- 0.17 cm2 to 1.53 +/- 0.48 cm2 (p < 0.001) and the mean
      mitral valve gradient decreased from 13.4 +/- 7.4 to 6.0 +/- 5.4 mmHg (p < 0.05).
      There were no deaths, one patient had cardiac tamponade after transseptal
      puncture and required emergency pericardiocentesis with successful percutaneous
      balloon valvotomy 6 months later. One patient had an unsuccessful valvotomy
      because the mitral valve could not be crossed and another patient had an
      inadequate dilatation. Our initial experience in percutaneous transseptal mitral
      valvotomy confirms the safety and efficacy of this new technique for the
      treatment of rheumatic mitral stenosis.

PMID- 8266148
TI  - Histopathologic coronary patterns in people with acute myocardial infarction and
      PTCA.
AB  - We studied coronary artery specimens histologically in 96 patients who died from
      acute myocardial infarction(AMI), to assess those who could benefit from in
      hospital percutaneous transluminal coronary angioplasty (PTCA). For the left
      anterior descending artery, old stenoses within 1 cm from its origin in 80 cases
      (83.3%), coronary narrowing over 90% and occlusive thrombi in 40 observations
      (41.6%) were seen. Left main artery showed proximal stenoses with an occlusive
      thrombus in 4 cases (41.6%). Left circumflex artery had stenoses within 1 cm from
      its origin in 32 cases (33.3%), with an occlusive thrombus 6 times (6.25%) and
      coronary narrowing 75%. Right coronary artery showed stenoses in the proximal and
      midportion respectively in 20 (20.8%) and 36 cases (37.5%), with 26 occlusive
      thrombi (27%) and coronary narrowing 85%. Four cases (4.16%) had minimal coronary
      changes. The patients who had one, two and three vessel disease were 32 (33.3%),
      32 (33.3%) and 28 times (29.16%) respectively. Only one-third of patients could
      benefit from PTCA.

PMID- 8266149
TI  - Can we afford to take short cuts in the management of stress urinary
      incontinence?
AB  - Is urodynamics necessary in the management of female stress urinary incontinence?
      This has remained a point of contention among urologists and gynaecologists
      alike. In this prospective study we evaluated 28 patients urodynamically to
      assess our diagnostic accuracy and to audit our intended management. These
      patients had complained solely or predominantly of stress incontinence. None of
      them had previous abdominal or vaginal surgery for stress urinary incontinence or
      a history suggestive of voiding disorder. All 28 of them were listed for either a
      Burch colposuspension or Stamey endoscopic bladder neck suspension operation
      based on demonstrating the sign stress incontinence clinically or radiologically
      on screening cystography. In all these cases the diagnosis of genuine stress
      incontinence was presumed and urodynamics would not have been performed
      preoperatively, if not for this study. As a result, there was a 21% overall
      change in the intended management. Routine but simplified urodynamics (to include
      pad test, provocative cystometry, uroflowmetry and residual urine measurement)
      would appear to be a pre-requisite of genuine stress incontinence surgery, even
      in patients complaining solely of stress incontinence.

PMID- 8266150
TI  - Cavernous transformation of the portal vein--sonographic findings.
AB  - Cavernous transformation of the portal vein may be seen following portal vein
      thrombosis. Ultrasound is a useful non-invasive procedure for demonstrating many
      abnormalities of the portal vein and surrounding structures. Two cases of
      cavernous transformation of the portal vein, diagnosed by ultrasonography, are
      presented.

PMID- 8266151
TI  - Meeting the challenge of diabetic blindness in the 90's.
AB  - Diabetic retinopathy is a leading cause of blindness in adults in Singapore and
      it is increasing in incidence. The difficulties and problems of screening for
      diabetic retinopathy were discussed as well as strategies laid out for overcoming
      this disease of national importance. Cost considerations and savings in health
      costs were also discussed. The authors suggested ways of instituting a nation
      wide Diabetic Screening and Education programme with hospital diabetic centre
      based clinic as well as a mobile screening service. A five-year screening plan as
      well as the costs and equipment necessary for such a programme were examined.

PMID- 8266152
TI  - Hepatitis C--the Malaysian story.
AB  - We studied the presence of Hepatitis C Virus (HCV) antibodies in a defined
      Malaysian population and examined the association, if any, between HCV and the
      Hepatitis B Virus (HBV), using sensitive recombinant DNA second generation Enzyme
      Immunoassay (EIA) test kits. This sero-prevalence study comprised 1,434 sera from
      eleven distinct groups comprising intravenous drug users (IVDU), haemophiliacs,
      male homosexuals, female prostitutes, healthy blood donors, staff of dialysis
      unit and laboratory personnel, chronic renal failure patients undergoing dialysis
      (CRFD), patients with liver cirrhosis, chronic active hepatitis, chronic
      persistent hepatitis and primary liver cancer. Except in laboratory personnel and
      dialysis staff, HCV antibodies were detected in each group of patients ranging
      from 3% in blood donors to 85% in IVDU. The main modes of HCV transmission
      identified were parenteral drug use, transfusion and/or dialysis related. The HBV
      was found to be the major viral etiological agent in 75% of chronic liver disease
      (CLD); while in 10% of cases both HCV and HBV were detected. HCV was implicated
      as the sole viral agent in only a small proportion (1.5%) of patients with
      chronic liver disease.

PMID- 8266153
TI  - Clinical experience with the Silc Cup Vacuum Extractor.
AB  - The relative merits of vacuum extraction have been extensively studied and its
      advantages analysed. These include its ease of application, encouragement of
      "autorotation" of the malpositioned foetal head and its safety for both foetus
      and especially the mother. One hundred and eighty-six vacuum extraction assisted
      deliveries were performed at the Department of Gynaecological Oncology & Urology,
      Kandang Kerbau Hospital, from 1988 to 1990 using the 50 mm Silicone Silc Cup
      Vacuum Extractor (Menox AB). Anaesthetic requirements were minimal with 97% of
      cases accomplished with local perineal anaesthesia. Maternal complications were
      very few and only 1.6% of cases had third degree lacerations. There was no
      maternal or foetal mortality. The most frequent foetal morbidity was neonatal
      jaundice (28%) with only 7% requiring phototherapy. Cephalohaematoma was found in
      8% and 2% had minor scalp abrasions. There were 3 infants with subaponeurotic
      haematoma who subsequently recovered uneventfully. Vacuum deliveries that were
      attempted but completed by forceps deliveries ("failed" vacuum extraction)
      accounted for 10% of total cases. The Silc cup vacuum extractor although not a
      replacement for all forceps manoeuvres offers a safe and efficient method of
      assisted delivery under the appropriate clinical circumstances.

PMID- 8266154
TI  - Decentralization of psychiatric services in Malaysia--what is the prospect?
AB  - Since the Government was implementing the policy of decentralization of
      psychiatric services, a large number of chronic schizophrenic patients failed
      community management because of the breakdown of family support. The rejected
      patients were admitted to the Old Persons' Home for protection because no other
      suitable places were available for them. In a follow-up study in one of the
      Homes, the one-year prevalence rate of treated psychiatric illness and
      schizophrenia was found to be 27.5% and 15.3% respectively. Lack of
      rehabilitation and community care facilities and inadequate staff in all
      categories were the root of the problem. The author foresees that the Government
      will face a serious problem in future to cater for the increasing number of
      chronic schizophrenic patients in the community if it does not take immediate
      action to improve mental health services in the country.

PMID- 8266155
TI  - Migratory fish bone in the thyroid gland.
AB  - Ingested fish bone in the upper aerodigestive tract is a common emergency
      condition encountered in our local otolaryngologic departments. Diagnosis is
      usually readily made from the clinical findings and radiology. Two cases of
      ingested fish bone causing acute, unilateral thyroidal swelling are reported
      here.

PMID- 8266156
TI  - Blood coagulation abnormalities associated with envenoming by Trimeresurus
      albolabris in Hong Kong.
AB  - Snake bites in Hong Kong are most commonly due to Tr. albolabris (White-lipped
      pit viper, bamboo snake). We studied 21 cases of envenoming by Tr. albolabris
      prospectively in order to document the incidence and severity of associated
      coagulation abnormalities. Eighteen patients (86%) had increased blood
      concentrations of fibrin degradation products (FDP) ranging from 10-40
      micrograms/l to greater than 200 micrograms/l (normal: less than 10
      micrograms/l), the majority of whom also had detectable soluble fibrin monomers.
      Among these 21 patients, 10 had decreased blood concentrations of fibrinogen
      ranging from 0.3 kg/l to 1.9 g/l (normal: 2-4 gl/l). In 11 cases (52%), the
      euglobulin clot lysis time was shortened (less than 150 minutes) in association
      with elevated blood concentrations of FDP (n = 10) and decreased circulating
      fibrinogen levels (n = 8). Thrombocytopenia and/or prolongation of prothrombin
      time (PT), activated partial thromboplastin time (APTT) and/or thrombin time (TT)
      were present in 10 patients (28%). Increased blood concentrations of FDP and
      decreased circulating fibrinogen levels were present in most of these cases.
      Envenoming by Tr. albolabris is therefore frequently associated with a
      coagulopathy compatible with increased fibrin/fibrinogenolysis. Measurement of
      blood concentrations of FDP is the most sensitive test for detecting the
      coagulopathy. There is, however, little correlation between the patterns of
      clinical manifestations and coagulation abnormalities although more severe
      clinical features were usually associated with high circulating FDP levels. Only
      one patient developed systemic bleeding but no fatality was observed. The
      coagulation abnormalities are usually correctable by replacement therapy. Further
      studies are required to study the mechanisms of this coagulopathy and its
      relationship with venom antigenaemia.

PMID- 8266158
TI  - Spontaneous pneumothorax: a review of 29 admissions into Hospital Universiti
      Sains Malaysia 1984-90.
AB  - Twenty-nine patients (16 males, 13 females) with spontaneous pneumothorax
      admitted into Hospital Universiti Sains Malaysia, Kubang Kerian, from September
      1984 to September 1990 were reviewed. Their ages ranged from newborn to 75 years.
      The commonest chief presenting symptom was dyspnoea (69%), followed by chest pain
      (35%). Four patients had chronic obstructive airway disease, 7 had pneumonia, 2
      had pulmonary tuberculosis, one patient had emphysema while 4 patients had
      multiple underlying lung disorders. The left and right lungs were involved with
      equal frequency. Bilateral pneumothorax occurred in one patient. Most patients
      had a single episode of pneumothorax but recurrent pneumothoraces occurred in 3
      patients (10%). Six patients were observed conservatively, 20 patients required
      chest tube insertion alone and 3 patients also required pleurodesis. Death
      occurred in 8 patients (28%) mainly due to coexisting infection and respiratory
      failure.

PMID- 8266157
TI  - Topical nasal anaesthesia for fibreoptic bronchoscopy: lignocaine spray or gel?
AB  - Lignocaine spray for anaesthetising the nasal mucosa for fibreoptic bronchoscopy
      often causes discomfort to the patient. We compared two techniques of applying
      nasal topical anaesthesia using either lignocaine spray (group A: 25 patients) or
      gel (group B: 30 patients) to assess patients' tolerance to the procedure. Both
      groups received 100 mg of lignocaine in the nostril, 40-50 mg to oropharynx, 120
      mg to vocal cords and 40-100 mg to trachea and bronchi. Throat anaesthesia was
      the most common unpleasant part experienced by both groups of patients (34.5%),
      followed by examination of bronchi (30.6%) and nasal anaesthesia (21.8%).
      Significantly more patients in group A experienced discomfort or pain during
      nasal anaesthesia as compared to group B (p < 0.001). Patients' tolerance to the
      bronchoscopy was similar in both groups and the examination was performed
      satisfactorily in all patients. Thus, lignocaine gel is a simple technique,
      effective and less irritating as compared to lignocaine spray for topical nasal
      anaesthesia.

PMID- 8266159
TI  - Sarcoidosis: a review of cases seen at the University Hospital, Kuala Lumpur.
AB  - Fourteen cases of sarcoidosis consisting of 7 male and 7 female patients with a
      mean age of 42.4 years were seen at the University Hospital from 1972 to 1990.
      There were 10 Indians, 2 Malays, and 2 Chinese. Twelve patients had thoracic
      involvement. The other common disease manifestations included weight loss,
      arthralgia, hepatomegaly, erythema nodosum, peripheral lymphadenopathy, and
      hypercalcaemia. At initial presentation, the disease was in radiographic stage I,
      II, and III in 8, 3 and one patient respectively. The Kveim test was positive in
      7 out of 9 patients. Eight patients required steroid therapy.

PMID- 8266160
TI  - The Singapore Renal Registry: an overview.
AB  - The Singapore Renal Registry (SRR) is created to collect and analyse information
      on incidence, prevalence, morbidity and mortality of End Stage Renal Disease
      (ESRD) in Singapore. Its objectives include the implementation of a consolidated
      renal disease data system, report on incidence and trends over time of renal
      disease, analyse aggregate data on effect of various modalities of therapy,
      identify problems and opportunities for special studies and research. The
      framework of the Registry encompasses the following areas: incidence,
      demographics and causes of ESRD, utilization of treatment modalities,
      institutions providing treatment, morbidity and survival rates of various
      treatment modalities, the paediatric sector, the private sector, international
      comparisons and research areas. This overview will present whatever existing data
      and renal statistics that are currently available on a regional or national
      basis. The collection of nationwide statistics will provide a database to
      formulate national averages of individual renal statistics. Statistics can also
      be collected to provide valuable data for planning and projection for future
      needs.

PMID- 8266161
TI  - Assessment of suicide risk.
AB  - Suicide is preventable and the first step in prevention is to identify those who
      are at risk. The psychiatrically ill are at high risk of suicide. The majority
      who commit suicide have given clear indications of suicidal intent shortly before
      the act. In the assessment of suicide risk the precipitating factor, the
      intensity of suicidal intentions, the patient's motivation for suicide and the
      lethality of the attempt have to be taken into consideration. Patients with
      significant suicide risk need to be hospitalized.

PMID- 8266162
TI  - Sudden onset of right bundle branch block. Acute pulmonary embolism.

PMID- 8266163
TI  - Respiratory failure from combined emphysema and pulmonary fibrosis.
AB  - An elderly man presented with hypoxemic respiratory failure and pulmonary
      hypertension. He was a heavy cigarette smoker and had been treated previously for
      pleuro-pulmonary tuberculosis. His lung volumes and airway function were normal.
      High resolution computer tomographic (HRCT) examination revealed combined upper
      lobe emphysema and lower lobe fibrosis. Routine pulmonary function tests may
      underestimate the degree of functional impairment in patients with combined
      emphysema and fibrosis. The HRCT examination however provided valuable
      information.

PMID- 8266164
TI  - Left ventricular outflow tract (LVOT) vegetations and spontaneous obliteration of
      a large ruptured intracranial mycotic aneurysm in a case of infective
      endocarditis.
AB  - A 10-year-old girl with mild aortic regurgitation presented with cerebral
      infarction. Two-dimensional echocardiography showed vegetations on the septal
      wall of the left ventricular outflow tract without involvement of the aortic
      valve itself. After successful antibiotic treatment the patient developed an
      intra-cranial haemorrhage due to rupture of a large intracranial mycotic
      aneurysm. Consent for surgical treatment of the mycotic aneurysm was not
      obtained. Twelve months later repeat angiography showed that the aneurysm had
      undergone spontaneous obliteration.

PMID- 8266165
TI  - Acute intestinal pseudo-obstruction due to malignant thymoma.
AB  - Acute intestinal pseudo-obstruction has been associated with various diverse
      aetiologies, including several types of malignancies. Malignant thymoma has never
      been reported before as a cause of acute intestinal pseudo-obstruction. We report
      here a case of malignant thymoma presenting as acute intestinal pseudo
      obstruction. Existing literature on malignant causes of intestinal pseudo
      obstruction is also reviewed and discussed.

PMID- 8266166
TI  - A rare wandering splenic cyst removed with laparoscopic assistance.
AB  - This is a report of the first case of a true cyst arising in a wandering spleen.
      Laparoscopic splenectomy was attempted. The spleen was mobilized under
      laparoscopic control and the cyst aspirated. Dissection of the pedicle was
      technically feasible. However, the procedure was aborted due to uncontrollable
      bleeding from a moderate-sized artery. Although the whole procedure was not
      completed laparoscopically, laparoscopic assistance facilitated extirpation of
      the spleen through a 5-cm oblique left iliac fossa incision in a minimally
      invasive fashion.

PMID- 8266167
TI  - Agenesis of the gall bladder with duplication cysts of the hepatic flexure--a
      case report and literature review.
AB  - A 24-year-old lady with recurrent upper abdominal pain, underwent surgery for
      cholelithiasis based on imaging diagnosis by ultrasound scanning. At laparotomy,
      the gall bladder could not be found either in its normal or ectopic locations.
      The diagnosis of agenesis of the gall bladder was confirmed by operative
      cholangiography. Duplication cysts of the hepatic flexure were discovered in the
      position normally occupied by the gall bladder. The stony hard faeces in the
      cysts were probably interpreted as gallstones on ultrasound. This rare condition
      is discussed and the importance of intraoperative cholangiography is stressed.

PMID- 8266168
TI  - Evaluation of therapies in the treatment of Helicobacter pylori associated non
      ulcer dyspepsia.

PMID- 8266169
TI  - Management of chronic urinary tract infection.

PMID- 8266170
TI  - Cancer--revealing the diagnosis.

PMID- 8266171
TI  - Laparoscopic cholecystectomy.

PMID- 8266172
TI  - Cancer: To tell or not to tell?
AB  - After a patient is diagnosed with a malignant illness, the physician is often
      left with the dilemma of how to communicate the diagnosis to the patient and the
      family. In the West, it is often the consensus that the patient be told. This is
      not necessarily true elsewhere, eg in Japan, the patient is often not told. A
      questionnaire survey was done to study how Singapore doctors feel about revealing
      the diagnosis of cancer to the patient. 90.4% of respondents will reveal the
      diagnosis to the family, while only 43.6% will inform the patient. The possible
      reasons are discussed.

PMID- 8266173
TI  - Experience with laparoscopic cholecystectomy at the Toa Payoh Hospital.
AB  - A retrospective analysis was done of 88 cases of laparoscopic cholecystectomy
      performed by the first author from November 1990 to March 1992 at the Toa Payoh
      Hospital. There were 61 female and 27 male patients; the average age was 47.1
      years. The most common presenting symptom was biliary colic (85.3%), followed by
      acute cholecystitis (10.2%) and gallstone pancreatitis (4.5%). In the vast
      majority of patients, the diagnosis was established by ultrasound (96.6%) while
      the remainder was diagnosed by oral cholecystography (3.4%). The operation was
      performed using the usual 4 puncture approach with the single-handed technique of
      dissection. Antibiotic prophylaxis with a broad-spectrum agent was used in all
      patients and there was no incidence of wound infection. A low complication rate
      of 4.5% was experienced--consisting of 1 case each of subcutaneous emphysema,
      abdominal colic, fever and bile duct injury. There was no mortality in our
      series. The conversion rate was 9.1% and this was due to our policy of performing
      laparotomy whenever the safety of laparoscopic surgery was in doubt. The mean
      duration of postoperative hospitalisation was 3 days and 7 days after
      laparoscopic and converted cholecystectomies respectively. The majority of
      patients (61.4%) returned to work after 2 weeks.

PMID- 8266174
TI  - Percutaneous balloon aortic valvotomy.
AB  - We report our first case of percutaneous balloon aortic valvotomy in a 72-year
      old Chinese female with critical aortic stenosis and carcinoma of the stomach.
      The presence of critical aortic stenosis (mean aortic pressure gradient of 65
      mmHg and an aortic valve area of 0.5 cm2) placed her at a high risk for
      gastrectomy. After balloon valvotomy of the aortic valve, the mean pressure
      gradient fell to 21 mmHg and the aortic valvular area increased to 1.0 cm2. She
      improved clinically and subsequently underwent surgery with no haemodynamic
      complication. Overseas experience has shown that percutaneous balloon valvotomy
      can be done with little technical difficulty and excellent patient tolerance,
      resulting in good haemodynamic and clinical improvement and a low acute
      complication rate. Present follow-up data however suggest significant mortality
      and restenosis rates at the end of one year. Percutaneous balloon aortic
      valvotomy (PBAV) has a significant though narrowly defined role in the management
      of patients with severe calcific aortic stenosis.

PMID- 8266175
TI  - Fatal varicella infections in Singapore.
AB  - Varicella (chickenpox) is common in Singapore. The annual incidence of reported
      cases for the period 1977-1990 ranged from 790 to 18,934, with a mean of 4,747.
      Mortality from chickenpox is rare. However, failure to recognise the severity and
      the potential complications of the disease, especially in immunocompetent
      patients, exists because of the common knowledge that chickenpox is a mild and
      self-limiting illness. We report six cases of fatal varicella in immunocompetent
      patients during the period 1988 to 1990.

PMID- 8266176
TI  - A follow up study of patients discharged from the Criminal Procedure Code.
AB  - Eighty-six male psychiatric patients discharged from the Criminal Procedure Code
      over a 5-year period were studied to determine their social, occupational and
      clinical outcome. The majority were young, single Chinese who had received little
      education and had suffered from schizophrenia. More than half had been
      hospitalised for up to 5 years. On discharge many were living with their
      relatives, 83% were working, 60% were socially isolated and about half were
      asymptomatic. Factors associated with their outcome were examined.

PMID- 8266177
TI  - A survey of postoperative wound infections in obstetrics and gynaecology--the
      Kandang Kerbau Hospital experience.
AB  - Postoperative wound infection is of great importance to both the surgeon and
      patient. This study covers 6,639 major operations in Kandang Kerbau Hospital,
      Singapore over a 12-month period. The overall wound infection rate was 2.26%. The
      highest wound infection rate occurred in hysterectomies and the lowest in
      laparoscopies. There was a good correlation between monthly caesarean wound
      infection rate and number of caesarean sections. Staphylococcus aureus was the
      most common organism isolated. The wound infection rate was also higher in
      crowded wards and among some surgeons. After distribution of the survey results,
      we noted a decrease in wound infection rate for some surgeons and a changing
      pattern in the use of antibiotics. A further study of other risk factors was
      encouraged.

PMID- 8266178
TI  - Serum thyroid stimulating hormone (TSH) in malnutrition: preliminary results.
AB  - This is a report of a cross sectional study involving 3 groups of children,
      moderately malnourished (BMI < 15), mildly malnourished (BMI 15-18) and well
      nourished (BMI > 18) to determine the differences in hormonal and biochemical
      parameters between the groups. The children were of age range from 7-17 years
      old. The children were from the same area with exposure to the same food,
      drinking water and environment. There were significant differences in the
      nutritional indices between the three groups. No differences were observed in
      levels of triiodothyronine (T3), thyroxine (T4) and T3:T4 ratio. Significant
      difference however was found in the TSH levels using highly sensitive IRMA TSH
      assays. Moderately malnourished children had higher TSH levels (p < 0.05)
      compared to mildly malnourished and well-nourished children. No difference was
      found between the mildly malnourished and well-nourished groups. There were no
      significant differences in serum cortisols done at similar times, fasting growth
      hormone and calcium. Serum alanine transminase (ALT) however was higher in
      moderately malnourished than in well-nourished children. Thus using highly
      sensitive IRMA TSH assays, we were able to detect differences in TSH levels even
      though T3, T4 and T3:T4 ratio, cortisol, growth hormone and calcium were normal,
      implying in moderately malnourished children, a higher TSH drive to maintain
      euthyroid state.

PMID- 8266179
TI  - Total and regional bone mineral densities in women with Colles' fractures: a
      comparative study with normal matched controls.
AB  - Total body and regional bone mineral densities (BMDs) were measured in 34 women
      with past Colles' fracture and 34 age- and sex-matched controls using the Norland
      XR-26 dual energy X-ray bone densitometer. The results showed that in patients
      with Colles' fracture affecting the left forearms, the BMD at the ultradistal 2.5
      cm region was significantly lower in the right forearm when compared with the
      left. This difference was not statistically significant among patients with
      fractures affecting the right or both forearms. The patients were also found to
      have lower BMDs in the femoral regions (0.600 +/- 0.010 g/cm2 in patients versus
      0.655 +/- 0.019 g/cm2 in controls), pelvis (0.679 +/- 0.009 g/cm2 in patients
      versus 0.728 +/- 0.020 g/cm2 in controls) and spine (0.710 +/- 0.018 g/cm2 in
      patients versus 0.780 +/- 0.030 g/cm2 in controls) when compared with the
      controls. No such difference could be demonstrated in the head, trunks or arms.
      These data suggested that women with past Colles' fracture might be more prone to
      fractures of spine and femoral regions. Bone mineral densities in the weight
      bearing regions, including femur and spine correlated strongly with each other
      (femoral neck versus lumbar spine, r = 0.64, p < 0.0001). Sites from the same
      anatomic regions, namely the femoral regions had highly correlated BMD values
      (femoral neck versus Ward's triangle, r = 0.91, SEE = 0.05, p < 0.0001), while
      poorer correlation was found among unrelated regions, such as between left
      ultradistal forearm and femoral neck (r = 0.43, SEE = 0.10, p < 0.05).

PMID- 8266180
TI  - A review of anaesthesia in ophthalmology.
AB  - In this article, we review the methods of anaesthesia commonly used in
      ophthalmology in Singapore. These include topical, local, regional and general
      anaesthesia. Topical and local anaesthesia is adequate for most outpatient
      procedures. The most common form of regional anaesthesia in Singapore is still
      retrobulbar anaesthesia. General anaesthesia is used in children and when more
      extensive procedures are performed.

PMID- 8266181
TI  - Outcome of patients with cervical spondylotic myelopathy seen at a rehabilitation
      centre.
AB  - A retrospective study was conducted on 21 patients with cervical spondylotic
      myelopathy to study the clinical characteristics of these patients and the
      influence of surgery and rehabilitation on their outcome. All the patients were
      50 years and above, with a mean age of 63.6 years. The most common presenting
      feature was weakness of all the limbs. Neckache was not a prominent finding.
      Although only 2 patients complained of bladder disturbance, 6 other patients were
      found to have bladder dysfunction after urodynamic assessment. Clinical outcome
      after surgery was 50% improved, 28% unchanged and 22% worsened. Fifty percent of
      the patients with voiding problems recovered after bladder training.
      Rehabilitation was significant in assisting in the recovery of patients after
      surgery. One patient had a disabling stroke 4 days after cervical surgery while
      another died of urinary tract infection while undergoing rehabilitation.

PMID- 8266182
TI  - Peripheral haemolysis, lipid peroxidation, iron status, and vitamin E in
      haemoglobin H syndromes in West Malaysia.
AB  - Following complete DNA characterisation patients with Hb H disease were assigned
      into two groups: deletional (alpha +/alpha o) and non deletional (HbCS/alpha o).
      Earlier studies have indicated that the group with (HbCS/alpha o) has more severe
      clinical problems. The serum malonyldialdehyde (MDA) levels, a secondary product
      of lipid peroxidation were within the normal range, though significantly higher
      levels of MDA were seen in the non-deletional type of Hb H disease when compared
      with the deletional type. Markedly low vitamin E levels were also seen in the
      former group. There were no significant differences in clinical severity may be
      attributed to an interplay of the accelerated destruction of damaged mature red
      blood cells secondary to the oxidative denaturation of Hb H and inclusion
      precipitation; higher levels of Hb H and more inclusion precipitation were seen
      in the group with (HbCS/alpha o). Low levels of vitamin E in the (HbCS/alpha o)
      group being due to its consumption in the neutralisation of free radicals formed
      with the oxidation of globin chains.

PMID- 8266183
TI  - Thrombocytopenia in sepsis: a predictor of mortality in the intensive care unit.
AB  - Disseminated intravascular coagulation (DIC) and thrombocytopenia are well-known
      complications of sepsis, but the relationship between these coagulation
      abnormalities and outcome have not been well documented. We studied the incidence
      of thrombocytopenia and DIC in our Medical Intensive Care Unit, and evaluated
      their usefulness as prognostic risk factors for mortality. Platelet count was not
      found to be an independent risk factor associated with overall mortality in the
      107 patients studied. In the sub-group of 53 patients with sepsis, 22 (42%)
      developed DIC, 31 (58%) developed thrombocytopenia (< 150,000 x 10(9)/L) and 27
      (51%) died. Thrombocytopenia was associated with presence of DIC (p = 0.003), but
      not with the type of infecting organism. The platelet count in non-survivors
      (mean +/- sem, 97 +/- 18 x 10(9)/L) was significantly lower than survivors (194
      +/- 27 x 10(9)/L, p < 0.005). Multiple regression analysis showed that
      thrombocytopenia was a risk factor for mortality, independent of the APACHE II
      score. The presence of DIC surprisingly was not an independent risk factor. We
      conclude that DIC and thrombocytopenia are common in our adult Medical Intensive
      Care patients with sepsis, but only the latter is a prognostic factor in addition
      to the APACHE II score. The incidence of DIC in our patients (mainly Chinese)
      seems to be more than that of 10 to 20% reported in other series of Caucasian
      patients. We would, therefore, like to emphasise the importance of platelet count
      as an prognostic risk factor in sepsis.

PMID- 8266184
TI  - Management of breech presentation at term.
AB  - The management of 159 consecutive women with singleton breech presentation
      occurring at 37 or more weeks of gestational age was reviewed. They were
      stratified into three groups: (a) caesarean section without trial of labour (87),
      (b) trial of labour resulting in caesarean section (21), and (c) trial of labour
      culminating in successful vaginal delivery (51). The criteria for allowing a
      trial of labour were described. Careful review of material and foetal variables
      indicated that a trial of labour in carefully selected patients resulted in
      vaginal delivery in 70.8% and that this was achieved without an increase in
      foetal or maternal mortality or morbidity.

PMID- 8266185
TI  - Magnetic resonance imaging of leptomeningeal metastases to the spine.
AB  - Neurologic complications of malignancy can result from paraneoplastic
      manifestations, cerebral metastases or leptomeningeal involvement. Radiologic
      evaluation by computerised tomography (CT) has proven to be an invaluable tool in
      cancer patients with neurologic symptoms. Myelography and CT myelography have
      been the main modalities for evaluating leptomeningeal metastases. The advent of
      magnetic resonance imaging (MRI) with contrast has provided an alternative
      modality for evaluation of leptomeningeal disease. MRI as compared to CT
      myelography is non-invasive and at least as sensitive. The findings in two
      patients with leptomeningeal involvement are reported to illustrate the value of
      MRI.

PMID- 8266186
TI  - Pill-induced esophageal ulcer.
AB  - We describe nine cases of esophageal injury associated with the ingestion of
      prescribed medications. Antibiotics were the most commonly implicated drugs.
      Odynophagia, retrosternal chest pain and dysphagia were the usual presenting
      symptoms. The typical endoscopic finding was that of discrete ulcers in the mid
      esophagus. All patients recovered uneventfully with discontinuation of the
      offending drug and symptomatic treatment. Drug induced esophageal injury should
      be considered in patients presenting acutely with the above mentioned symptoms
      and having discrete esophageal ulcers on endoscopy.

PMID- 8266187
TI  - Mental Health Service in Singapore.
AB  - The year 1928 marked the beginning of the mental health service in Singapore.
      From a large asylum which provided mainly custodial care the mentally ill were
      managed by a handful of expatriate medical pioneers and nurses. Drugs were
      limited and hospitalisations lasted years. The scene has changed tremendously
      over the last six decades. Today the Mental Health Service in Singapore is
      largely provided by the public sector with contributions from private and
      voluntary organisations. It provides a comprehensive and integrated programme
      consisting of both hospital-based and community-based treatment programmes with
      the objectives to promote good mental health for everyone as well as to provide
      the best possible treatment for those afflicted with mental illnesses of all
      types. With the rapid development of community-based mental healthcare, several
      changes have taken place to reflect this trend. Besides introducing a wide range
      of community support services and greater liaison with primary care givers, the
      need to educate medical students and doctors, members of the public, people
      involved in healthcare in the voluntary sector and others about mental health and
      illness has been recognised to be an important component in the delivery of good
      mental healthcare. As a step forward the National Mental Health Programme has
      been launched by the Ministry of Health in 1993 to further improve the mental
      health service that is currently available (Fig 1). The newly established
      Institute of Mental Health will serve as the education, training and research arm
      of the National Mental Health Programme. Together with the new Woodbridge
      Hospital, mental healthcare in the future will be professionally organised,
      coordinated and community-orientated.

PMID- 8266188
TI  - Myths and realities of electroconvulsive therapy.
AB  - With its introduction in 1938 electroconvulsive therapy became a powerful form of
      treatment for depressive illness and the major psychoses. Its use over the years
      has declined with the development of effective antidepressant and antipsychotic
      drugs. It still has a place in psychiatric treatment where urgent resolution of
      symptoms is indicated in certain conditions. The mechanism by which it exerts its
      therapeutic effect remains unknown.

PMID- 8266189
TI  - Low QRS voltages--differential diagnosis. Pericardial effusion.

PMID- 8266190
TI  - Torsade de pointes and sudden death associated with diabetic autonomic diarrhoea-
      a case report.
AB  - A 68-year-old diabetic and hypertensive woman presented with chronic autonomic
      diarrhoea, syncope and palpitations which were associated with QT prolongation
      and recurrent episodes of torsade de pointes. She was on glibenclamide,
      indapamide and probucol (for type V hyperlipidaemia). Despite intravenous
      infusions of potassium, lignocaine and amiodarone, the unstable rhythm persisted.
      However, intravenous magnesium sulphate with small doses of intravenous
      propranolol terminated the torsade de pointes. She was stabilised but following
      discharge she relapsed, and upon re-admission, succumbed to intractable
      ventricular fibrillation. Early recognition and aggressive treatment of this
      condition is emphasised. Multiple aggravating factors ie autonomic diarrhoea
      resulting in severe potassium and magnesium depletion, kaliuretic effect of
      indapamide, probable QT prolongation associated with diabetic autonomic
      neuropathy and probucol; probable underlying coronary artery disease and
      heightened emotional and sympathetic discharge could have contributed to this
      very unstable ventricular arrhythmia and sudden death.

PMID- 8266191
TI  - Pasteurella multocida septicaemia following a dog bite.
AB  - Bite wounds are often mistakenly considered innocuous. However, they are
      frequently complicated by infection which may be serious. We describe a case of
      Pasteurella multocida septicaemia with myopericarditis following a dog bite.
      Treatment of the infection as well as active support of myocardial function led
      to a successful outcome.

PMID- 8266192
TI  - Benign teratoma of the fallopian tube: a case report.
AB  - A benign teratoma of the fallopian tube in a 33-year-old woman with primary
      subfertility is reported. This is the first case reported in Singapore. The
      features of benign teratoma of the fallopian tube is discussed.

PMID- 8266193
TI  - Lymphangioleiomyomatosis with chylous ascites.
AB  - A 41-year-old Malay housewife presented with recurrent chylous ascites and
      progressive cachexia over 17 years. A diagnosis of lymphangioleiomyomatosis (LAM)
      was established by laparotomy where biopsy of the liver, peritoneum and adhesions
      from previous surgery showed smooth muscle proliferation in the blood vessels and
      lymphatics. Clinically and radiologically, there was no evidence of pulmonary
      involvement. She was treated with dietary fat restriction and medium-chain
      triglycerides. This is the first case of LAM reported in Malaysia.

PMID- 8266194
TI  - Prophylactic antimicrobial agents.

PMID- 8266195
TI  - Paracetamol poisoning.

PMID- 8266196
TI  - SMA Lecture. No man is an island.

PMID- 8266197
TI  - Paracetamol poisoning and hepatotoxicity in Chinese--the Prince of Wales Hospital
      (Hong Kong) experience.
AB  - From 1989 to 1991, 104 Chinese patients were admitted to the Prince of Wales
      Hospital with paracetamol poisoning. Only 11 subjects had a plasma paracetamol
      concentration above the published treatment line. Intravenous N-acetylcysteine
      (NAC) was completely effective when given within 8 hours (3 patients), while late
      treatment with NAC at 16 and 26 hours after overdose (2 patients) was ineffective
      in preventing liver damage as evidenced by elevations in plasma alanine
      transaminase concentrations. Of the 6 patients receiving NAC between 10 to 15
      hours, two had liver damage. Two other subjects who presented late or in whom a
      plasma paracetamol concentration was not measured also developed liver damage.
      Fortunately, none of these 6 subjects developed hepatic encephalopathy. We
      recommend that a standard protocol be readily available for junior hospital staff
      to use when treating patients with paracetamol overdosage.

PMID- 8266198
TI  - The glucose challenge test: a screening test for gestational diabetes mellitus.
AB  - The 50g glucose challenge test (GCT) was evaluated as a method to screen for
      gestational diabetes in 540 low-risk pregnant women to establish its sensitivity
      and specificity, as well as to establish a relevant threshold plasma glucose
      value above which a diagnostic 75g oral glucose tolerance test (OGTT) would be
      indicated. If a threshold of 140 mg/dl is used, the diagnostic yield would be
      28.5%. At a threshold of 130 mg/dl, the diagnostic yield fell to 25.4%; the
      sensitivity rose to 87.7% and the specificity declined to 67.1%. There was
      progressive increase in diagnostic sensitivity when the GCT was performed after
      24 weeks without significant decrease in specificity. In low-risk populations, a
      50g GCT should be performed between 24-28 weeks gestation.

PMID- 8266199
TI  - Evaluation of yoga therapy programme for patients of bronchial asthma.
AB  - A study of the effect of yoga therapy programme on 46 indoor patients of chronic
      bronchial asthma on exercise capacity, pulmonary functions and blood gases was
      conducted. Exercise capacity was measured by 3 tests: (i) 12 min walk test (12
      md); (ii) physical fitness index (PFI) by modified Harvard step test; and (iii)
      Exercise-Liability index (ELI). Yoga therapy programme resulted in a significant
      increase in the pulmonary functions and exercise tolerance. A one-year follow-up
      study showed a good to fair response with reduced symptoms score and drug
      requirements in these subjects. It is concluded that yoga therapy is beneficial
      for bronchial asthma.

PMID- 8266200
TI  - Excimer laser photorefractive keratectomy in Singapore--a new treatment modality
      for myopia.
AB  - BACKGROUND: Myopia is a national epidemic in Singapore. Photorefractive
      Keratectomy (PRK) for the treatment of myopia using the Argon Fluoride Excimer
      Laser commenced in January 1992 at the Singapore National Eye Centre. METHODS: An
      open, prospective, non randomised clinical trial to assess the efficacy,
      predictability, stability, and safety of PRK for the correction of myopia between
      -2.0 to -6.0 dioptres. RESULTS: One hundred and fifty-five eyes of one hundred
      and thirty-five patients underwent PRK between January and September 1992, of
      which thirty-one had completed at least six months of follow-up. Twenty-nine of
      the thirty-one patients (93.5%) achieved an unaided visual acuity of at least
      6/12. Twenty-six patients (83.9%) were within 1 dioptre of emmetropia. There was
      an initial over-correction in all patients which regressed to a plateau at around
      three or four months. Corneal haze did not pose a significant problem. Three
      patients had ocular hypertension, and another developed a mild allergic reaction
      to the antibiotic-steroid ointment. CONCLUSIONS: Excimer Laser Photorefractive
      Keratectomy is a very effective, fairly predictable, stable and safe surgical
      method for the treatment of myopia.

PMID- 8266201
TI  - Clinical experience with automated percutaneous discectomy.
AB  - This study was performed to evaluate a group of patients undergoing automated
      percutaneous lumbar discectomy. All patients had disc pathology at L4/L5 and
      L5/S1 documented on CT scan and/or MRI. The range of follow-up was between 3
      months and 20 months. The average hospital stay was 2 days (range 1-3 days). A
      total of 21 patients underwent the procedure and 18 were available for
      assessment. Of these, 12 patients improved. Of the patients that did not, two
      subsequently underwent surgical discectomy. There was one failed procedure but no
      other intra- or post-operative complications. The results of the study indicate
      that percutaneous discectomy has a demonstrable low morbidity and can be
      performed under local anaesthesia. However, proper patient selection is important
      for successful results.

PMID- 8266202
TI  - Acute myocardial infarction survival rate and complications after streptokinase
      therapy in Hospital Universiti Sains Malaysia, Kelantan--a comparative study.
AB  - Thrombolytic therapy is a well-established therapy in acute myocardial infarction
      (AMI), reducing mortality and infarct size. This study is a retrospective
      analysis of survival and complications after the use of streptokinase at Hospital
      Universiti Sains Malaysia. Streptokinase was first used here in March 1990.
      Between then and February 1992, 126 patients were admitted to the Coronary Care
      Unit. Thirty-two patients who fulfilled our criteria for thrombolytic treatment
      were given an hour intravenous infusion of 1.5 MU streptokinase, and started on
      aspirin. A control group of 64 patients selected from before March 1990, and
      matched for age, sex and site of infarct, was given standard therapy. The
      survival at 4 weeks post-AMI was 91% in the streptokinase therapy group and 91%
      in both groups (p > 0.05). The complications encountered were reperfusion
      arrhythmias (2 patients), hypotension(1), maculopapular rash(1) and gum
      bleeding(1). None of these complications were statistically increased when
      compared to the control group and none resulted in the death of a patient. We
      conclude that streptokinase therapy can be given safely in a rural Malaysian
      setting. Our survival and complication rates are comparable with other published
      series.

PMID- 8266203
TI  - Validation of APACHE II score in a surgical intensive care unit.
AB  - The APACHE II scoring system was applied to 301 surgical intensive care
      admissions over a 9-month period. The mean age of patients admitted was 52.39
      years (SD 19.3) and the mean duration of stay was 5.37 days (SD 8.93). The
      overall mortality was 17.27%. The mean APACHE II scores for survivors was 12.94
      (SD 7.43) and non-survivors 28.19 (SD 10.43). There was good correlation between
      expected mortality predicted by the APACHE II system and observed mortality (r =
      0.9732). Using a predicted risk criterion of 0.5 to distinguish between those
      predicted to survive and die, of the 45 patients predicted to die, only 30
      actually did so. No patient survived with an APACHE II score of more than 40 and
      with a predicted risk of death greater than 0.87. We found the APACHE II system
      useful for evaluating ICU performance and risk stratification for the purpose of
      therapeutic trials but not as a triage tool.

PMID- 8266204
TI  - Hepatitis B virus infection in patients with systemic lupus erythematosus.
AB  - Sera from 76 patients with systemic lupus erythematosus (SLE) were examined for
      HBsAg, anti-HBsAb and total anti-HBcAB by radioimmunoassay. Fifteen patients
      (19.7%) had one or more of these serological markers of HBV infection. This is
      comparable to the sero-prevalence in 100 sex- and age-matched healthy individuals
      (19%). There was no significant difference in the prevalence of HBV infection in
      patients who had received immunosuppressants compared with those who had not.
      Patients who had received transfusion of blood or blood products had a higher
      prevalence of serological markers but this was not statistically significant.

PMID- 8266205
TI  - Renal arteriovenous fistula following kidney biopsy in systemic lupus
      erythematosus.
AB  - Patients with lupus nephritis frequently undergo renal biopsies. A rare
      complication of this procedure is the development of renal arteriovenous
      fistulas. We report two patients with systemic lupus erythematosus (SLE) who
      developed this vascular complication several years after renal biopsy.

PMID- 8266206
TI  - Prospective study of the aetiology of adult community acquired bacterial
      pneumonia needing hospitalisation in Singapore.
AB  - A prospective survey of 96 consecutive adult patients with community acquired
      pneumonia requiring hospitalisation was carried out at National University
      Hospital, Singapore. Causative pathogens were identified in 58% of patients.
      Mycobacterium tuberculosis was the most common pathogen (21%), followed by
      Streptococcus pneumoniae (12%), Haemophilus influenzae (5.2%), Mycoplasma
      pneumoniae (5.2%) and Staphylococcus aureus (4.2%). Gram-negative organisms
      (apart from Haemophilus influenzae) were found in 10% of pneumonia patients. More
      than half of the patients had pre-existing illness, the most common was diabetes
      mellitus (21%).

PMID- 8266207
TI  - Profuse epistaxis: an argument for conservative medical management.
AB  - A review of 10 years' experience of all patients with profuse epistaxis requiring
      hospitalisation in a tertiary care centre in India is presented. There were 106
      patients among which only 72% of cases had associated medical illness.
      Hypertension (44%) and bleeding diathesis (11%) were found to be the most
      frequently associated aetiological medical conditions noted in this study.
      Although there is controversy regarding the optimum treatment in profuse
      epistaxis in literature, our experience suggests that it can be successfully
      managed with conservative medical management alone and surgical intervention with
      its potential complications may not be necessary in most cases.

PMID- 8266208
TI  - Abdominal hysterectomy: indications and complications.
AB  - This retrospective study was conducted to evaluate the indications and
      complications for non-radical abdominal hysterectomy. Between 1 July 1990 and 30
      June 1991, 176 women underwent abdominal hysterectomy in our Department. The
      indications for hysterectomy, the conservation of ovaries, type of concurrent
      procedures, choice of incision, choice of fascial closure in midline incisions,
      use of prophylactic antibiotics and complications of abdominal hysterectomy were
      analysed. The most common indication was uterine leiomyomata followed by pelvic
      endometriosis and premalignant disease. Haemorrhage requiring transfusion was the
      commonest intra-operative complication. Unintended surgical procedures occurred
      in almost 3% of patients.

PMID- 8266209
TI  - Xanthogranulomatous pyelonephritis in a Malaysian population.
AB  - Xanthogranulomatous pyelonephritis is a clinico-pathological entity that is
      gaining awareness amongst urologists worldwide. It is an unusual chronic
      inflammatory lesion involving the kidney that destroys renal parenchyma and may
      mimic renal carcinoma. It is usually seen in middle-aged women and is associated
      with urinary tract infections and urinary calculi. Most reports and reviews of
      this condition come from the West; this study reviews the incidence and
      presentation of the condition in a Malaysian population.

PMID- 8266210
TI  - Progressive optic atrophy associated with juvenile diabetes mellitus: report of
      two cases among first cousins.
AB  - Two first cousins both suffering from insulin dependent diabetes mellitus since
      early childhood developed progressive optic atrophy from the age of 5 and 9 years
      respectively. They had similar ophthamological features which include optic
      atrophy with cupping, paracentral scotomata, and total achromatopsia. One patient
      also had stunted growth, delayed puberty and psychiatric disorder. Neither had
      diabetes insipidus and deafness. It is suggested that they may be a variant of
      DIDMOAD (Diabetes Insipidus, Juvenile Diabetes Mellitus, Optic Atrophy,
      Deafness).

PMID- 8266211
TI  - A practical approach to the management of psychoses.
AB  - The importance of differentiating between the organic and functional psychoses is
      stressed. The salient features of the different types of functional psychoses are
      discussed and the management of the psychoses is approached from biological,
      psychological and sociological angles at the same time. Corroboration of history
      by concerned relatives or friends is deemed indispensable.

PMID- 8266212
TI  - The psychiatric complications of epilepsy.
AB  - The psychiatric complications of epilepsy are varied but may be considered under
      two main groups--those directly related to ictal activity and those that occur
      during the inter-ictal period. Epilepsy and psychiatry are also similar in that
      they cause a great deal of social difficulties and restriction in terms of
      activities and employment opportunities because of the associated stigma and
      prejudice. The various complications are discussed and illustrated with case
      studies where appropriate.

PMID- 8266213
TI  - T wave inversion in a woman with giddiness and weakness. Hypokalemia.

PMID- 8266214
TI  - Atypical pneumonia due to Chlamydia pneumoniae: a case report.
AB  - A first case of Chlamydia pneumoniae pneumonia in Malaysia is reported. The
      diagnosis was made by a significant change in C. pneumoniae antibody titre. The
      infection responded well to a course of erythromycin.

PMID- 8266215
TI  - Laparoscopic-assisted right hemicolectomy--a case report.
AB  - Laparoscopic colon resection has recently attracted attention as a viable option
      to open colectomy due to its excellent postoperative recovery. We report the
      first right hemicolectomy done laparoscopically in Asia in a 62-year-old female
      patient with Dukes-B2 caecal carcinoma. Bowel sounds were present on the first
      post-operative day (POD) and diet was resumed on the third. The patient was
      discharged on the fourth POD. There was no complication of anastomotic leakage or
      wound infection.

PMID- 8266216
TI  - Dysphagia and chronic schizophrenia: a case report.
AB  - It is known that dysphagia in schizophrenia could result from acute or tardive
      dystonic reactions or parkinsonism as a result of neuroleptics. This case
      illustrates that dysphagia may be inherent in schizophrenia itself and not
      necessarily be due to neuroleptics.

PMID- 8266217
TI  - Acute presentation of tuberous sclerosis: case report.
AB  - Incomplete form of tuberous sclerosis (TS) may present with acute complications
      such as haematuria, retroperitoneal haemorrhage or pneumothorax. Such cases may
      pose diagnostic difficulty. A patient with incomplete form of TS without any
      cerebral impairment who presented as an acute surgical abdomen is reported. The
      diagnostic criteria of TS are reviewed. Visceral manifestations of TS including
      acute complications are discussed. The importance of recognising such
      presentations is stressed.

PMID- 8266218
TI  - Adenosquamous carcinoma of the ileum--a case report.
AB  - Small bowel malignancies are very uncommon and adenosquamous carcinomas of the
      small intestine are extremely rare. We report the second case of an adenosquamous
      carcinoma of the ileum in a 77-year-old Chinese male.

PMID- 8266219
TI  - Trade, population flow and transnation malaria control.

PMID- 8266220
TI  - Economic analysis of malaria control for migrant workers in eastern Thailand.
AB  - A randomized, double-blind field trial was carried out to compare the economic
      impact of permethrin-treated nets with that of untreated nets as a method of
      malaria control. The study was conducted in 261 long-term migrant workers and 138
      seasonal agricultural migrant workers in the eastern rural areas known to be
      highly endemic for multidrug-resistant Plasmodium falciparum infection. One
      hundred and twenty-six longterm migrants and 59 seasonal migrants used treated
      nets, while 135 and 79, respectively, used untreated nets. The impregnated-nets
      program was cost-saving as well as offering improved effectiveness. The net
      benefit of using a treated net was US$1.17 per worker from the Malaria Division's
      perspective and US$1.61 per worker from the worker viewpoint. The use of
      impregnated nets with large-scale primary health care programs likely will be the
      most cost-effective and cost-beneficial method for controlling malaria in eastern
      Thailand.

PMID- 8266221
TI  - Mefloquine monitoring in acute uncomplicated malaria treated with Fansimef and
      Lariam.
AB  - Mefloquine levels were compared between Plasmodium falciparum malaria patients
      with sensitive response and those with treatment failure who received 3 drug
      regimens of mefloquine (46 patients with MSP 3 tablets (Fansimef), 38 and 34 with
      mefloquine (Lariam) 750 mg and 1,250 mg). Mefloquine concentrations on Day-1 in
      any regimens in patients with treatment failure were significantly lower than
      those from the sensitive response, whereas there was no difference in the
      concentrations on Day-7. However, MIC values of mefloquine prior to drug
      treatment were comparable in both groups. The study suggests that pre-treatment
      in vitro sensitivity testing was a non-reliable indicator of clinical outcome.
      Mefloquine concentration on the first day after treatment is a better predictor
      of the treatment outcome.

PMID- 8266222
TI  - Mefloquine levels in patients with mefloquine resistant Plasmodium falciparum in
      the eastern part of Thailand.
AB  - A total of 99 patients with uncomplicated falciparum malaria who attended the
      malaria clinic in Bo Rai, Trat Province were treated with a single oral dose of
      MSP 3 tablets (Fansimef; equivalent to 750 mg of mefloquine) concurrently with
      primaquine (30 mg). The aim of the study was to detect RII and RIII types of
      response with 3 tablets of MSP. Seven (8.1%) and 22 patients (25.3%) had RII and
      RIII types of response, respectively, and 58 (66.8%) had no parasitemia on Day-7
      (S or RI response). Mefloquine concentrations on Day-3 after treatment in
      patients in the S/RI group were significantly higher than those with early
      treatment failure (RII, RIII), with the respective mean (SD) values of 1,959
      (696) and 1,622 (863) ng/ml. The mean concentrations of mefloquine in these
      patients with RII and RIII types of response were higher than those with a
      sensitive response in a previous study. The result suggests that Plasmodium
      falciparum strains in this part of the country are highly resistant to mefloquine
      and that blood levels of mefloquine on Day-3 may also be a good indicator of
      treatment outcome in this particular area.

PMID- 8266223
TI  - Treatment of acute uncomplicated falciparum malaria with a short course of
      artesunate followed by mefloquine.
AB  - The clinical results of this study indicate that a half-dose regimen of
      artesunate followed by mefloquine produces an acceptable cure rate when compared
      to other commonly available drugs for treating acute uncomplicated falciparum
      malaria in Thailand. The 90% cure rate was comparable to the results with either
      a full dose of artesunate (600 mg over 5 days) or mefloquine (25 mg/kg in divided
      doses six hours apart) as well as the combination of quinine-tetracycline
      administered for seven days. This abbreviated regimen, however was less effective
      than the full dose regimen of both drugs previously reported.

PMID- 8266224
TI  - Serum protein polymorphisms and malaria in Madya Pradesh, India.
AB  - The relationship of serum protein polymorphisms to the presence of malaria
      antibodies was studied in 473 muria gond tribal subjects from Bastar district,
      Central India, an area endemic for both P. falciparum and P. vivax infection. A
      control group of 100 subjects in Delhi, which has a low prevalence of malaria,
      was also studied. Serum proteins (transferrin, haptoglobin and albumin) were
      analyzed for polymorphic variants by starch gel electrophoresis. Malarial
      antibodies were assayed by enzyme linked immunosorbent assay (ELISA), while thin
      blood films were screened for the presence of malaria parasites. Among serum
      proteins transferrin CD variant showed significant correlation with malarial
      infection. There were no significant differences observed between Hp1 and Hp2
      variants of haptoglobin in relation to presence of malarial antibodies.
      Statistical analysis for albumin variants was not attempted because the number of
      individuals showing abnormal bands was small.

PMID- 8266225
TI  - Changing seroepidemiology of hepatitis A virus infection in Thailand.
AB  - Hepatitis A is an infectious disease commonly found in many developing countries.
      The infection usually is asymptomatic in children and only a small percentage has
      clinical hepatitis of varying severity. Hepatitis A infection becomes more
      symptomatic with increasing age. We studied hepatitis A antibody prevalence in
      many population groups of Thailand and investigated the changing patterns of
      hepatitis A antibody in comparison with previous seroepidemiological surveys in
      the past decade. The antibody prevalence in Bangkok and in the rural areas of
      Thailand had markedly declined among the children and adolescents studied. Only
      one-fifth to one-fourth of children and adolescents had antibody to hepatitis A.
      The prevalence differed from that of a decade ago. These data probably reflect
      the marked improvement of hygienic conditions and effective health education,
      which have reduced exposure to HAV infection among young children. When an
      effective hepatitis A vaccine with long lasting immunity becomes available,
      subgroups of the populations at risk of infection will be the targets for
      immunization.

PMID- 8266226
TI  - Randomized, single-blind comparison of the immunogenicity and reactogenicity of
      20 micrograms and 10 micrograms doses of hepatitis B vaccine in adolescents.
AB  - The study compares the effect of two different doses of a recombinant DNA
      hepatitis B vaccine (Engerix-B) administered to 320 healthy adolescents divided
      randomly into two equal groups, using the 0, 1 and 6 month's vaccination
      schedule. Initially the larger dose elicited protective levels of antibody in a
      greater proportion of subjects. The seroprotection rates were significantly
      higher at both months 1 (17.6% v/s 9.2%) and 2 (68.8% v/s 56.7%). The difference
      was especially relevant 6 months after the start of the vaccination schedule when
      a 92.4% seroprotection rate was obtained in the 20 micrograms dose group, whereas
      only 78.3% of subjects in the 10 micrograms dose group had protective antibody
      levels. Furthermore there were significant differences in anti-HBs geometric mean
      titers for seroconverters at months 6 (109 v/s 56mlU/ml) and 7 (4774 v/s
      2705mlU/ml). However one month after the third vaccine administration, both doses
      produced similar high seroprotection rates (97.9% and 97.1%, respectively). The
      difference in the generally mild overall reactogenicity for the 2 dose levels was
      not remarkable although the higher dose produced more local symptoms. The
      conclusion from the study was that the 10 micrograms dose produces a very good
      antibody response in adolescents, provided the full vaccination course of three
      doses, according to a 0, 1 and 6 month's schedule, is administered. However, the
      20 micrograms dose should be used if compliance to the full course is in doubt
      since a 92.4% seroprotection rate can be obtained with 2 injections compared to
      only 78.3% with the 10 micrograms dose.

PMID- 8266227
TI  - Prevalence of human herpesvirus 6 in Thai people and its correlation with human
      immunodeficiency virus type 1 infection.
AB  - Human herpesvirus 6 (HHV-6) is a human herpesvirus isolated from patients with
      various lymphoproliferative disorders and acquired immunodeficiency syndrome
      (AIDS). The prevalence of HHV-6 infection and its correlation as a cofactor in
      pathogenicity of HIV infection was investigated in serum samples from 365 healthy
      volunteers at various age groups, 50 persons at risk for HIV-1 infection, and 90
      HIV-1 seropositive individuals. Sera were screened and titrated for antibodies
      against HHV-6 by a standard indirect immunofluorescence assay on an acetone fixed
      HHV-6 infected HSB2 cells. The data show high prevalence of HHV-6 in Thailand
      (71.7%) and the infection is acquired early in life. Prevalence of anti-HHV-6 IgG
      antibodies was not strikingly different among people at risk for HIV infection,
      asymptomatic HIV-1 infected cases, and aged-matched controls with low risk for
      HIV-1 infection. The AIDS cases showed high titers of anti-HHV-6 IgG antibody and
      high rates for presence of anti-HHV-6 IgM antibody (33.3%) which suggests higher
      prevalence of HHV-6 infection by either reactivation of an earlier HHV-6
      infection or a new primary infection.

PMID- 8266228
TI  - The value of potency testing of poliomyelitis and measles vaccines as an integral
      part of cold chain surveillance.
AB  - The Virology Division in the Institute for Medical Research, Kuala Lumpur,
      Malaysia performs potency tests on oral polio vaccines and live attenuated
      measles vaccines. Since these potency tests were introduced in 1981 a total of
      752 tests have been performed on vaccine samples from peripheral immunization
      centers. Of 165 representative vaccine samples sent for potency evaluation after
      a cold chain breakdown 154 (87%) passed minimum potency requirements recommended
      for immunization of infants. In the absence of potency evaluation, those vaccines
      exposed to temperatures higher than the recommended storage range would be
      discarded, perhaps resulting in unnecessary wastage and economic loss. Results of
      the vaccine potency evaluation has enabled health authorities to indirectly
      monitor cold chain efficiency and ensure the high quality of viral vaccines used
      in our childhood immunization program.

PMID- 8266229
TI  - Western blot analysis of antigens specifically recognized by natural immune
      responses of patients with Japanese encephalitis infections.
AB  - Specific recognition of antigenic proteins of Japanese encephalitis virus (JEV)
      by JE patients was investigated by using non-reducing and reducing Western
      immunoblot analysis. Under non-reducing conditions, the profile of JEV proteins
      recognized comprised E (52 kDa), NS1 (45 and 41 kDa), NS3 (66.2 kDa) and NS5 (103
      and 97.4 kDa). When recognition patterns of sera from JE and dengue patients were
      compared, only slight differences between JE and dengue sera were found (under
      non-reducing conditions), involving only the 66.2 kDa protein: to this protein,
      JE sera exhibited greater reactivity, but not in greater frequency, than did
      dengue sera. In contrast, cerebrospinal fluid (CSF) from JE patients showed more
      differences from JE sera: CSF antibody lacked recognition of the 41 kDa protein
      and had lower frequencies, as well as less reactivities to several other
      proteins. These results suggested that restricted populations of lymphocytes were
      localized in the central nervous system of JE patients. The effect of reducing
      agent (2 beta-mercaptoethanol) on the recognition patterns of those groups of
      sera was also analysed: the reducing agent affected all the proteins mentioned
      above, however, the effects were not uniform. It is proposed that JE and dengue
      sera may recognize different epitopes on some or all of these proteins. Such
      differences cannot be detected by Western immunoblot analysis, but it would be
      feasible to test this hypothesis using epitope mapping with synthetic peptides in
      a multi-pin ELISA. Analysis in this fine detail is essential for designing
      improved JE vaccines.

PMID- 8266230
TI  - Hypertension in Asir region, southwestern Saudi Arabia: an epidemiologic study.
AB  - A population study was carried out to determine the prevalence of hypertension
      among Saudis at primary health care level in the Asir region, Southwestern Saudi
      Arabia. All primary health care centers (PHCCs) were visited (238 PHCCs). Data
      were collected in relation to the updated Saudi population census for 1991.
      Chronic case registries were revised to identify existing cases of hypertension
      by age and sex till the end of 1991. Results showed that the prevalence of
      hypertension amounted to 2.4% among Saudis aged 45 years and more. Males and
      females aged 45 years and more living at high altitude had a significantly higher
      risk of developing hypertension (p < 0.05) compared to those living at sea level.

PMID- 8266231
TI  - Seasonal changes in serum and erythrocyte potassium among renal stone formers
      from northeastern Thailand.
AB  - Hypocitraturia, hypokalemia and low urinary excretion of potassium are common
      findings in nephrolithiasis in Northeastern Thailand. However, intracellular
      potassium has not been studied. We measured serum potassium, erythrocyte
      potassium, 24-hour urinary excretion of sodium, potassium, citrate, ammonium,
      titratable acid and pH in 17 nephrolithiasis patients from Northeastern Thailand
      during 2 seasons: the cool and hot months. There were no significant differences
      in urinary pH, ammonium, titratable acid, citrate and potassium during these 2
      seasons. However, hypocitraturia and hypokaliuria were observed in the majority
      of cases in both periods. Seasonal variation in serum potassium, erythrocyte
      potassium, urine volume and urinary excretion of sodium was observed. Values were
      significantly lower in the hot months. In the cool months, the urinary excretion
      of citrate correlated linearly with that of potassium (r = 0.696, p < 0.002).
      Such a correlation was not found in the hot months. We concluded that
      extracellular and intracellular potassium depletion might be present in these
      patients and is greater during the hot than during the cool months. The
      pathogenesis may be multi-factorial.

PMID- 8266232
TI  - Nutritional status of Kadazan children in a rural district in Sabah, Malaysia.
AB  - The nutritional status of 896 Kadazan children below 6 years of age from 23
      villages of Tambunan District were studied. When stunting and wasting were
      defined as those who were below two standard deviations of height-for-age and
      weight-for-height (Waterlow et al, 1977) and based on the National Center for
      Health Statistics reference population, 67.6% of boys and 66.8% of girls were
      stunted while 12.3% of boys and 8.3% of girls were wasted. Weaning foods and
      toddler feeding practices were unsatisfactory. The role of health education on
      child care and feeding practices is emphasized.

PMID- 8266233
TI  - Utilization of maternal and child health facilities by the urban poor of Kuala
      Lumpur.
AB  - A survey conducted to assess the extent which the urban poor in rapidly expanding
      Kuala Lumpur utilize maternal and child health services available to them. The
      sample consisted of 1,380 households with children below 6 years and yielded
      1,233 children below 6 years of age. 74% of the children had been delivered in
      government hospitals and 86% of the pregnancies had antenatal care in
      governmental establishments. 89.2% had BCG immunization before they were 1 year
      old but 13.3% had not received DPT by that age. Immunization was mainly done in
      government clinics. The overall immunization coverage for the whole of Kuala
      Lumpur is expected to be higher than these figures limited to the urban poor.
      Health planners should increase health facilities in the city to accommodate the
      expanding population. There is a need to continually campaign for immunization to
      improve coverage among the urban poor.

PMID- 8266234
TI  - Effect of chemotherapy on helminth reinfection in slums and villages in
      Bangladesh.

PMID- 8266235
TI  - Intestinal parasitic infections in Campalagian district, south Sulawesi,
      Indonesia.
AB  - Intestinal parasitic infections were surveyed in the inhabitants of 3 coastal and
      2 inland villages of Campalagian District, South Sulawesi, Indonesia, in July
      1992. A total of 398 fecal samples were examined by using Kato-Katz thick smear,
      Harada-Mori culture and agar-plate culture techniques. Protozoan cysts were
      examined by formalin ether concentration technique on 380 fecal samples. Soil
      transmitted helminth infections were highly prevalent with the overall positive
      rates as follows: Ascaris lumbricoides 25.3%, Trichuris trichiura 59.3%, hookworm
      68.3% and Strongyloides stercoralis 2.3%. Eight species of protozoan were
      detected with the overall prevalence as follows: Entamoeba histolytica 10.9%, E.
      hartmanni 16.3%, E. coli 31.9%, Endolimax nana 12.5%, Iodamoeba buetschlii 5.4%,
      Giardia lamblia 4.6%, Chilomastix mesnili 0.8% and Blastocystis hominis 18.0%. In
      the inland villages, prevalence of hookworm infection was higher than Ascaris and
      Trichuris infections, while in the coastal villages Trichuris infection was
      predominant. Egg count revealed that the infection level was light in most of the
      hookworm and Trichuris carriers. Prevalence of lavatories among houses appeared
      to be inversely proportional to the prevalence of hookworm infection. Meanwhile,
      the incomplete structure of the lavatories might result in contamination of
      environment with Ascaris and Trichuris eggs. Harada-Mori culture was the most
      efficient method in the detection of hookworm infection compared to other
      techniques. Both Necator americanus and Ancylostoma duodenale were found in all
      villages, but the former was the predominant species. An adult pinworm was
      detected by agar-plate culture of feces. Two types of pinworm males,
      corresponding to Enterobius vermicularis and E. gregorii, were observed.

PMID- 8266236
TI  - Serosurvey of some major zoonotic infections in children and teenagers in Bali,
      Indonesia.
AB  - One hundred and ninety serum samples, mainly from children and teenagers, from
      northeast Bali were tested for the presence of antibodies against five zoonotic
      agents: Brucella abortus, Coxiella burnetii, Toxoplasma gondii, Toxocara canis
      and Trichinella spiralis. All children were negative for brucellosis and Q fever.
      A high prevalence rate was found for toxocariasis (63.2%) and trichinosis
      (19.5%). Antibody prevalence against T. gondii was found to be rather low (3.1%).
      To our knowledge, this is the first evidence of toxoplasmosis, toxocariasis and
      trichinosis infection in humans on Bali. Eating habits and poor hygiene may
      explain the frequency of parasitic infestations in the children and teenagers in
      Bali.

PMID- 8266237
TI  - Spatial and temporal variations in prevalence, intensity and aggregation of
      microfilaria in the human host.
AB  - The prevalence, intensity and the frequency distribution of microfilaria (mf) of
      Wuchereria bancrofti in the human blood and their variation in time (pre-vector
      control, control and post control periods) and space have been examined. The
      prevalence and intensity showed significant variation between time and different
      areas of urban Pondicherry. The significant reduction in the prevalence and
      intensity of microfilaremia in the areas of high endemicity indicated that the
      effect of vector control was well marked in these areas. The distribution of
      microfilaria in human population was adequately described by the truncated
      negative binomial prior to interruption of transmission, and the dispersion
      parameter 'k' of the negative binomial varied between 0.17 and 0.68. A change in
      the distribution was observed after the 5 years of vector control, during which
      the transmission was completely interrupted. The increased 'k' values suggest
      that the distribution of mf is influenced by the degree of exposure to infection.
      Therefore, comparison of changes in the parameter 'k' can be considered as an
      additional tool for evaluating the control operations aimed at interrupting the
      transmission.

PMID- 8266238
TI  - Hepatosplenic lesions induced by experimental Schistosoma malayensis in rabbits.
AB  - Two groups of three rabbits each were infected with 250 cercariae of the Baling
      and Koyan strain of Schistosoma malayensis. Changes induced by both strains
      included periportal hepatocellular necrosis and fibrosis. Vascular changes such
      as portal phlebitis and thrombophlebitis and varying degrees of pericholangitis
      were also present. Amyloid deposition was noted. A comparative study of the
      changes induced in rabbits by S. malayensis, S. mekongi and S. japonicum showed
      that the hepatic lesions induced by the Baling strain of S. malayensis were
      similar to that induced by S. japonicum, and were more severe than that induced
      by S. mekongi or the Koyan strain.

PMID- 8266239
TI  - The use of topical phenytoin as an adjunct to immobilization in the treatment of
      trophic leprosy ulcers.
AB  - A total of 30 leprosy patients (controls n = 16; topical phenytoin n = 14) with
      trophic ulcers on the feet were investigated to ascertain the efficacy of topical
      phenytoin powder in the healing of ulcers. The ulcers in the two groups were
      matched for initial size. Healing patterns were assessed by determining changes
      in depth and planar (surface) dimensions at weekly intervals over a three week
      study period. Results indicate that while immobilization of the ulcer site is
      effective in promoting ulcer healing, additional use of topical phenytoin
      accelerates the healing process. There may however be non-responders to topical
      phenytoin.

PMID- 8266240
TI  - The distribution of Malassezia furfur and Malassezia pachydermatis on normal
      human skin.
AB  - Clinically normal skin of 200 volunteers, age range 20-30 years, were studied.
      Skin samples were taken by swabbing ten different sites and examined for the
      presence of Malassezia furfur and Malessezia pachydermatis by culture. All of the
      subjects studied harbored M. furfur at every site tested, and had high counts on
      the head region and upper trunk. The strains isolated could be divided on the
      basis of culture characteristics into three distinct groups. Only 12% of the
      subjects carried M. pachydermatis with very low counts at sites on the head and
      palm.

PMID- 8266241
TI  - The spectrum of Aeromonas-associated diarrhea in tropical Queensland, Australia.
AB  - During a twelve-month period (1 July 91-30 June 92), feces from 912 persons from
      the Townsville region in the dry tropics of Queensland, Australia were evaluated
      by culture and 45 (4.9%) immunocompetent patients were found to be carrying
      Aeromonas in their stools. All patients were index cases and no secondary cases
      from household or close contact of index cases were identified. Eight patients
      (9.3%) were from Palm Island, an Aboriginal community, and 37 (4.5%) were from
      the essentially Caucasian population of Townsville. This is a significant
      difference in incidence of cases between the two population groups. Infection
      occurred mainly in two age groups: the under five-year-old (27 cases) and the
      over 25-year-old age group (17 cases). Except for one patient, all cases of Palm
      Island Aborigines were children less than five years of age, and 13 of these
      infants (48%) were less than 1 year old, but none were neonates. Of the 37
      Townsville patients, 20 cases (54%) were in the under five-year-old group. Signs
      and symptoms of Aeromonas-associated diarrhea in patients where Aeromonas was the
      sole pathogen isolated were diarrhea sometimes with vomiting, absence of fever
      and of fecal leukocytes and blood in the stools. No cases of Aeromonas-associated
      diarrhea with dysentery were encountered. After rotavirus (12.3%), Aeromonas was
      the second most common enteric pathogen detected, but was only marginally more
      common than Giardia and Salmonella. Of the aeromonad isolations, 50% were
      Aeromonas hydrophila, 22% were A. sobria, and 28% were A. caviae.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266242
TI  - Serosurveys of spotted fever and murine typhus in local residents of Taiwan and
      Thailand compared with Japan.
AB  - To estimate the prevalence of spotted fever (SF) and murine typhus (MT)
      rickettsioses in Southeast Asia, we performed serosurvey by immunoperoxidase test
      on local residents in Taiwan and Thailand, comparing them with those of Japan. In
      Japan, the prevalence of antibodies (1:80 as cut-off level) to some SF/MT
      antigens was noticeable in Japanese SF-endemic areas or a high-risk groups. In
      Tainan, Taiwan, SF antibodies were not so prevalent (3.5 to 4.4%), but MT
      antibodies were more prevalent (23.9%). In Chiang Rai in northern Thailand SF
      antibodies were markedly prevalent (9.0 to 21.3%); the reactivity with Thai tick
      118 strain alone was 8.2%, but MT was less (2.5%). These results suggest that
      these rickettsioses may be latently distributed in various parts of Asia.

PMID- 8266243
TI  - Insecticide susceptibility status of Anopheles koliensis (Diptera: Culicidae) in
      northeastern Irian Jaya, Indonesia.
AB  - Anopheles koliensis, an important malaria vector in the interior region of Irian
      Jaya, Indonesia, was evaluated for susceptibility to three different insecticide
      compounds using the standard World Health Organization diagnostic test kit and
      pretreated impregnated papers. A series of tests were conducted in Arso PIR I, a
      transmigrant settlement 60 km south of Jayapura, from January 1988 to May 1989.
      All compounds were tested at the recommended diagnostic dosage and exposure time.
      An. koliensis were susceptible to 1.0% fenitrothion at two hour exposure (N =
      358) and 5.0% malathion at one hour exposure (N = 371) after the 24-hour holding
      period. Significant resistance to DDT was observed in both the An. koliensis and
      Culex quinquefasciatus populations. Approximately 30% of the An. koliensis
      population (N = 468) was resistant to 4% DDT at both one and two hour exposures.
      These findings indicate that routine use of DDT in Arso PIR I for indoor residual
      house spraying may be of limited effectiveness, in part, because of physiological
      resistance. However, use of an alternative insecticide will be more expensive and
      might prove equally ineffective because of the exophilic behavior of the species.
      This is the first confirmed report from repeated observations of DDT resistance
      in An. koliensis from Indonesia.

PMID- 8266244
TI  - Field evaluation of a microgel droplet formulation of Bacillus sphaericus 1593M
      (Biocide-S) against Anopheles culicifacies and Anopheles subpictus in south
      India.
AB  - A microgel droplet formulation of Bacillus sphaericus 1593M (Biocide-S) was field
      tested at two different doses viz, 0.22 and 0.43 g/m2 in casuarina pits against a
      malarial vector Anopheles (Cellia) culicifacies Giles, and An. (Cel.) subpictus
      Grassi in coconut garden pits in the coastal areas of South India. Both doses
      significantly reduced the abundance of late instars and pupae of An. culicifacies
      for 3 and 5 weeks respectively. A significant reduction was recorded in the
      abundance of late instars and pupae of An. subpictus for 2 and 3 weeks
      respectively.

PMID- 8266245
TI  - Seasonal abundance of dengue vectors in Manila, Republic of the Philippines.
AB  - The dengue vectors Aedes aegypti and Ae. albopictus were surveyed within the city
      of Manila from August 1985 to July 1987. Survey techniques included ovitraps,
      indoor resting collections, Fay traps, and larval surveys. Aedes aegypti was the
      principal container breeder within the residential areas, while Ae. albopictus
      predominated in cemeteries. The ovitrap was very effective in detecting the
      presence of Ae. aegypti, but not in measuring population changes during the year.
      Indoor resting and Fay traps show a low population of Ae. aegypti from February
      through May, during the dry season, and higher populations from June through
      September, during the rainy season. The most common indoor containers holding
      larvae were flower vases, while metal or glass containers were the most common
      outdoors. Dengue transmission appears to be closely related to rainfall, with
      cases increasing about 2 months following the onset of the rainy season.

PMID- 8266246
TI  - Beta 0-thalassemia due to a cytosine deletion in codon 41 associated with
      hemoglobin E.

PMID- 8266247
TI  - Simian malaria infection in wild caught Macaca fascicularis and Presbytis spp in
      Malaysia.

PMID- 8266248
TI  - Phagocytosis of malaria-infected erythrocytes in rodent malaria.

PMID- 8266249
TI  - Schistosoma mansoni: development in Japanese Hartley strain of guinea-pigs.

PMID- 8266250
TI  - Role of retrovirus HTLV-1 in African spastic paraplegia.

PMID- 8266251
TI  - Treatment of neurocysticercosis with a two week course of albendazole.
AB  - Ten cases of cerebral cysticercosis, treated with 2-week course of albendazole,
      were reported. The results were excellent. 9 patients were responded to this
      regimen in both the clinical outcomes and CT scan findings. These results
      indicated that a 2-week course of albendazole is effective for treatment of
      neurocysticercosis.

PMID- 8266252
TI  - Eosinophilic cerebrospinal fluid pleocytosis and primary amebic
      meningoencephalitis.

PMID- 8266253
TI  - Acute methamidophos poisoning caused by contaminated green leafy vegetables.

PMID- 8266254
TI  - [Admission].

PMID- 8266255
TI  - [Guiding through a pregnancy].

PMID- 8266256
TI  - [Echography and prenatal diagnosis].

PMID- 8266257
TI  - [A new birth].

PMID- 8266258
TI  - [The stay in the hospital].

PMID- 8266259
TI  - [Shared responsibility].

PMID- 8266260
TI  - [Maternity psychologist].

PMID- 8266261
TI  - [Rites and representations of labor pain. The pretty hurt. 1].

PMID- 8266262
TI  - [Recent difficulties in school].

PMID- 8266263
TI  - [When a child is to be born, that is quite a story].

PMID- 8266264
TI  - The effects of isotonic saline volume resuscitation in uncontrolled hemorrhage.
AB  - In the present study, the effects of early isotonic fluid resuscitation on
      uncontrolled hemorrhage in rats under pentobarbital anesthesia were assessed.
      Forty-five female Sprague-Dawley rats, weighing between 230 and 295 grams, were
      anesthetized and cannulated. Uncontrolled hemorrhage was initiated by a 75
      percent tail resection, and the rats were randomly divided into three groups:
      group 1, no resuscitation; groups 2 and 3, saline solution administration over a
      four minute interval (40 and 80 milliliters per kilogram, respectively), 15
      minutes after the initial hemorrhage. Changes in blood pressure, blood loss and
      mortality rates were recorded and the rats were observed for up to 360 minutes.
      The mortality rates were 73, 40 and 53 percent for groups 1, 2 and 3,
      respectively. The corresponding average survival times for these groups were 135,
      195 and 178 minutes. The difference between groups 1 and 2 were above the 95
      percent confidence level using the chi-square test (mortality) and the Student's
      t test. The average total blood loss in groups 2 and 3 was 31.7 and 41.4
      milliliters per kilogram of body weight; when compared with group 1 (24.6
      milliliters per kilogram), the difference between the two latter groups (1 and 3)
      was statistically significant with a p < 0.001. These results suggest that early
      infusion of isotonic fluid improves survival time and reduces short term
      mortality in uncontrolled hemorrhage regardless of the associated increases in
      blood loss.

PMID- 8266265
TI  - Searching for the best operative modality for severe hepatic injuries.
AB  - In the United States, there has been a trend away from hepatic resection in favor
      of nonresectional techniques for patients with severe hepatic injury. However, we
      consider that hepatic resection is more effective and safer, provided that it is
      performed appropriately. In 1985, we adopted a new protocol for patients
      undergoing hepatectomy for severe hepatic injury (class IV and V by Moore's
      classification). This protocol consists of criteria for hepatectomy and
      application of adjunctive procedures. Since 1985, we have treated 130 patients
      with hepatic injuries, including 24 patients (20 who underwent hepatectomy) with
      class IV hepatic injury and 13 patients (ten who underwent hepatectomy) with
      class V injury. The mortality rates of the patients with hepatic injury with
      class IV and V injury were 21 and 46 percent, respectively. The mortality rates
      for patients who underwent hepatectomy, including formal lobectomy to treat class
      IV and V injury, were 5 and 33 percent, respectively. The mortality rates of the
      patients with hepatic injury with class IV injury and the hepatectomy patients in
      both groups were significantly improved after introduction of the protocol. In
      addition, the outcome was superior to those reported by several trauma centers in
      the United States. Thus, we conclude that hepatectomy, including formal
      lobectomy, should be considered as one of the preferred treatment modalities for
      severe hepatic injury.

PMID- 8266266
TI  - The continuing challenge of aneurysms of the popliteal artery.
AB  - This report is an analysis of 252 popliteal artery aneurysms (PAA) in 167
      patients treated surgically at the University Hospital in Zurich during a 27 year
      period from 1965 to 1991. The predominance of male patients (95 percent) was
      consistent with that of other reports. PAA were bilateral in 51 percent of the
      patients and were associated with aneurysms at other sites in 38 percent.
      Atherosclerosis was by far the most common cause (98 percent). PAA were
      symptomatic in 75 percent of the patients, the predominant findings being
      ischemia from emboli, thrombosis or rupture. Primary amputation was required in
      23 extremities. Surgical reconstruction with bypass was performed for 229 PAA. A
      secondary amputation was necessary in 18 limbs. The risk of complications from
      popliteal aneurysms, and the good results from surgical treatment suggest that a
      revascularization procedure in the asymptomatic stage should be recommended
      unless specific contraindications exist. We conclude that surgical treatment
      should be performed in symptomatic and asymptomatic PAA larger than 2 centimeters
      in diameter. Long term results of surgical reconstruction are improved if an
      autogenous saphenous vein is used and if reconstruction is performed before the
      occurrence of complications. Polytetrafluoroethylene prostheses should be used
      when an autologous saphenous vein is not available. The use of Dacron (polyester
      fiber) grafts is no longer indicated.

PMID- 8266267
TI  - Percutaneous endoscopic gastrostomy for gastric decompression in metastatic
      gynecologic malignancies.
AB  - We report our experience with 28 patients using percutaneous endoscopic
      gastrostomy (PEG) for decompression of gastrointestinal obstruction as a result
      of carcinomatosis secondary to gynecologic malignancy. PEG could be performed
      successfully in 26 of the 28 patients. In two patients, intubation was not
      possible for technical reasons and the procedure was aborted. PEG is more cost
      effective and safer than operative tube placement in these patients and offers a
      significantly better quality of life to the patient than does chronic nasogastric
      intubation.

PMID- 8266268
TI  - The influence of vagotomy on basal and postprandial pancreatic secretion and
      plasma levels of gastrointestinal hormones in conscious rats.
AB  - This study was conducted to investigate the effect of vagotomy on basal and
      postprandial pancreatic secretion and plasma levels of gastrointestinal hormones.
      Thirteen rats underwent vagotomy and 12 underwent sham operation. All of the rats
      were prepared with gastric and pancreatic fistulas. Before and after an
      intragastric infusion of liquid meal, pancreatic fluid and protein outputs and
      plasma levels of cholecystokinin and gastrin were measured. Vagotomy induced a
      delay and a decrease in postprandial responses in pancreatic volume and protein
      outputs. Vagotomy had no effect on basal and postprandial plasma levels of
      cholecystokinin. Basal and postprandial levels of plasma gastrin were
      significantly increased after vagotomy, but the postprandial patterns of gastrin
      release were not significantly different between the two groups. Vagal regulation
      may be important in the basal gastrin release but is not involved in basal
      release of cholecystokinin or postprandial releases of gastrin and
      cholecystokinin. The current results indicate that vagotomy influences
      postprandial pancreatic secretion. This effect is probably the result of
      interrupted vagus-mediated reflexes between the intestinal tract and the
      pancreas.

PMID- 8266269
TI  - The effect of heat load and dehydration on hypertonic saline solution treatment
      of controlled hemorrhagic shock.
AB  - Small volume hypertonic saline solution has been suggested for initial effective
      resuscitation of hemorrhagic shock. The effect of hypertonic saline solution in
      controlled hemorrhagic shock was studied in rats subjected to dehydration or
      heat, or both. The rats were randomly divided into four groups--group 1 (n = 19),
      normal rats; group 2 (n = 21), water deprivation for 12 hours; group 3 (n = 20),
      heating at 37 degrees C. for five hours, and group 4 (n = 19), water deprivation
      for 12 hours and heating at 37 degrees C. for five hours. Controlled hemorrhagic
      shock was induced in all rats by arterial bleeding of 15 milliliters per kilogram
      and the rats were divided into three treatment subgroups--group a was untreated,
      group b was treated with 5 milliliters per kilogram 0.9 percent NaCl and group c
      was treated with 5 milliliters per kilogram 7.5 percent NaCl. Arterial bleeding
      of 15 milliliters per kilogram in group 1 resulted in decrease in mean arterial
      pressure (MAP) to 44 +/- 2 millimeters of mercury (p < 0.001) and pulse rate to
      280 +/- 13 per minute (p < 0.01). A similar decrease in MAP and pulse rate was
      observed in all four groups. Infusion of hypertonic solution (HTS) in group 1c
      was followed by an increase in MAP to 89.0 +/- 9.7 milliliters of mercury (p <
      0.01) in 15 minutes. This was significantly higher than infusion of normal saline
      solution in group 1b (p < 0.01) or untreated group 1a (p < 0.01). This difference
      remained significant also after 45 minutes from infusion (p < 0.05 and p < 0.05,
      respectively). The increase in MAP in response to HTS in group 1c after 15
      minutes was significantly higher than the rise in groups 2c (p < 0.05), 3c (p <
      0.05) and 4c (p < 0.05). This difference in response to HTS remained significant
      45 minutes from infusion in groups 3c (p < 0.05) and 4c (p < 0.05), but not in
      dehydrated rats in group 2c. Arterial bleeding did not alter serum sodium
      significantly in all four groups. Infusion of HTS in group 1c was followed by an
      increase in serum sodium from 149.1 +/- 1.4 to 161.1 +/- 2.4 milliequivalent per
      liter (p < 0.001), while infusion of HTS in group 4c, where serum sodium was
      initially elevated to 157.1 +/- 3.0 milliequivalent per liter, did not further
      elevate the serum sodium level.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8266270
TI  - Early carcinoma of the stomach.
AB  - We analyzed data on 423 Japanese patients with early carcinoma of the stomach
      with respect to clinicopathologic features and prognosis. All patients were
      treated in the clinics at which we work. The upper one-third of the stomach was
      less frequently involved. Therefore, partial gastrectomy was performed more often
      in patients with early carcinoma of the stomach than in those with advanced
      carcinoma of the stomach. The differentiated type of carcinoma of the stomach was
      more frequent and grew expansively. Lymph node metastasis was noted in 11.6
      percent of the patients, lymphatic vessel involvement was evident in 13.5 percent
      and extensive lymph node dissection (R2 or R3) was performed in 86.0 percent. The
      15 year survival rate for patients with early carcinoma of the stomach was 89.0
      percent. Lymph node metastasis, differentiated tumor type and patient age proved
      to be independent prognostic factors, as determined by multivariate analysis.
      Increased detection of early carcinoma of the stomach in its curable stages may
      be achieved through gastrointestinal series and endoscopy for symptomatic
      patients. A close follow-up evaluation is essential to detect recurrences, even
      when a curative resection is performed.

PMID- 8266271
TI  - Gallstone recurrence after shock wave therapy.
AB  - Fifty-three patients with complete clearance of all gallstone fragments after
      combined extracorporeal shock wave lithotripsy (ESWL) oral litholytic therapy
      were included in the study. Eight patients had recurrence of gallstones within
      the first year at follow-up evaluation. The rate of gallstone recurrence was 15.2
      percent within the first year. Four of these eight patients reported biliary
      pain, the other four remained asymptomatic. The incidence of gallstone recurrence
      was high in patients who had multiple stones before ESWL treatment (p < 0.05).
      Age above 60 years was also associated with a higher rate of gallstone recurrence
      (p < 0.05).

PMID- 8266272
TI  - Use of the appendix in urologic reconstructive operation.
AB  - Advances in genitourinary operation have allowed use of an appendicovesicostomy
      in patients requiring chronic catheterization for bladder emptying. Recent
      discussions of the appropriateness of incidental appendectomy have ignored the
      potential usefulness of the appendix as a catheterizable stoma. We present our
      experience with the Mitrofanoff principle to illustrate the advantages of an
      appendicovesicostomy and make a plea against incidental appendectomy in certain
      patient groups.

PMID- 8266273
TI  - The vascular-interstitial pH gradient during and after hemorrhagic shock.
AB  - The interstitial fluid space (IFS) response to hemorrhagic shock (HS)-induced
      metabolic acidosis is reported. Prenodal skin lymph was used as a mirror of IFS
      changes. Twenty-three conditioned dogs had a reservoir HS insult followed by
      resuscitation with shed blood, crystalloid solution containing a total of 6.5
      milliequivalents of sodium per kilogram of body weight and 250 milliliters of
      autologous banked blood. Prenodal skin lymph pH, oxygen tension (pO2), carbon
      dioxide tension (pCO2), bicarbonate level (HCO3) and flow rate measured before
      shock, during HS and in postresuscitation in 17 dogs in group 1 were compared
      with simultaneous samples of central venous blood. Peripheral venous values were
      not measured in dogs in group 1 to preclude any effects that local dissection
      might have on prenodal skin lymph. Six dogs in group 2 underwent the same HS and
      resuscitation model; the sequential changes in central mixed venous pH and
      lymphatic pH were compared with peripheral venous pH. HS caused metabolic
      acidosis; in group 1, the mixed venous pH decreased to 7.16 and in group 2, the
      peripheral venous pH decreased to 7.03. In contrast, the prenodal skin lymph pH
      in both groups was maintained at PS levels (7.51). Mixed venous pO2 decreased
      sharply with HS, whereas skin lymph pO2 was maintained. Maintained prenodal skin
      lymph pH and pO2 during HS-induced metabolic acidosis implies that the IFS
      undergoes stoichiometric changes. This facilitates the preferential adherence of
      highly charged proteins, like albumin, to the matrix to maintain cellular
      homeostasis.

PMID- 8266274
TI  - The effect of floppy Nissen fundoplication on esophageal and gastric motility in
      gastroesophageal reflux.
AB  - Thirty-five patients with gastroesophageal reflux (GER) proved on ambulatory
      esophageal hydrogen monitoring were surgically treated by a floppy Nissen
      fundoplication. Postoperatively, reflux and symptoms related to it were almost
      completely abolished. Transient bloating syndrome was observed in five instances.
      The operation significantly improved esophagitis (p < 0.01), increased lower
      esophageal sphincter pressure (p < 0.01) and increased amplitude of esophageal
      peristalsis (p < 0.01). However, postoperative motility of the esophagus as
      detected by manometry was still impaired as compared with that for the control
      group. Delayed esophageal transit did not improve postoperatively, although no
      dysphagia was accounted. Impaired esophageal motility in GER was associated with
      delayed gastric emptying, which, however, improved postoperatively. It is
      concluded that esophageal and gastric motor abnormalities are rather primary
      disorders in GER. After successful fundoplication, esophageal dysmotility,
      aggravated by reflux esophagitis, improves to some extent, while gastric emptying
      is enhanced.

PMID- 8266275
TI  - Temporary redistribution of hepatic or pancreatic blood flow by vascular
      occluders during intra-arterial chemotherapy for carcinoma of the liver or
      pancreas.
AB  - Surgically placed inflatable vascular occluders temporarily increased or
      restricted the target volume for intra-arterial therapy for tumors in the liver
      and pancreas. Proximal occlusion of the common hepatic artery directed retrograde
      flow from the cannulated gastroduodenal artery into a variant left hepatic artery
      in one patient with carcinoma of the liver. Occlusion of the distal splenic
      artery and common hepatic artery after distal gastrectomy with cannulation of the
      left gastric artery gave selective perfusion of the tumor-bearing pancreatic head
      in three patients. The occlusions had no untoward effects and the regional
      infusions seemed to retard local tumor growth.

PMID- 8266276
TI  - An improved method of diaphragmatic plication.

PMID- 8266277
TI  - A brief historical perspective and a comparison of the current systems of
      surgical training in Great Britain, Germany and the United States of America.
AB  - The surgical training programs of Great Britain, Germany and the United States
      were designed with some considerable exchange of ideas between these countries.
      However, although they share certain similarities, these training schemes have
      developed their own unique features and characteristics. Since the profession of
      surgery has entered a new period of transition, the education of its trainees
      will require judicious modifications in the near future.

PMID- 8266278
TI  - Results of venous thrombectomy in the treatment of deep vein thrombosis.
AB  - Despite the infrequent use in the United States, venous thrombectomy seems to
      have a beneficial effect in carefully selected patients with acute iliofemoral
      thrombosis. The final decision to proceed with venous thrombectomy should be
      based on a balanced analysis of two factors--the characteristics of the thrombus
      and the characteristics of the patient. First, the diagnosis of acute deep vein
      thrombosis must be unequivocally established preoperatively. Accurate anatomic
      localization is usually achieved with venography, but duplex Doppler examination
      may be sufficient in selected instances. Second, the distribution of thromboses
      should be determined. Venous thrombectomy should be considered only in instances
      of deep vein thrombosis involving the iliofemoral venous segment. Thrombectomy
      for venous thrombosis below the inguinal ligament has not been consistently
      beneficial. Third, the age of the thrombus should be estimated. This can usually
      be accomplished though a careful analysis of the clinical history, but may be
      corroborated by duplex Doppler or venographic features of the thrombus. Venous
      thrombectomy should rarely be attempted if the age of the thrombus is thought to
      be greater than 72 hours. Unfortunately, in many instances the clinical history
      substantially underestimates the actual age of the underlying thrombus. Fourth,
      patient characteristics must be assessed preoperatively. While venous
      thrombectomy can usually be accomplished using local anesthesia, substantial
      shifts in fluid and acid base balance may be poorly tolerated by elderly, frail
      patients. In the setting of widespread metastatic disease, rethrombosis rates may
      be too high to justify thrombectomy in some patients.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8266279
TI  - Use of cholesterol-lowering drugs United States, 1992.
AB  - More than 26 million prescriptions for cholesterol-lowering drugs were dispensed
      in the United States in 1992. These drugs represented 3.7 percent of the total
      pharmaceutical sales market, with retail costs exceeding $1.5 billion. Since 1988
      both the number of doctor visits for disorders of lipid metabolism and the total
      number of prescriptions for cholesterol-lowering drugs have steadily increased.
      Mevacor and Lopid continue their market dominance of such drugs and accounted for
      almost 76 percent of the total number of 1992 cholesterol-reducing drug
      prescriptions dispensed. The rate of new prescriptions for cholesterol-lowering
      drugs was 65.1 per 1,000 population across the country; the highest rate was
      reported in the East North Central area and the lowest in the Pacific states.
      Among all specialists, general or primary care internists, family and general
      practice physicians and cardiologists were the most frequent prescribers of
      cholesterol-lowering drugs.

PMID- 8266280
TI  - Heart disease mortality: international comparisons.
AB  - In the United States mortality from diseases of the heart has declined 42 percent
      in women and 43 percent in men since 1968. This encouraging trend occurred among
      all racial groups and was experienced in virtually all age categories. Because of
      comparable progress in other countries, this substantial United States
      achievement has not resulted in any significant recent gains in international
      ranking of the United States and other highly industrialized countries.
      Nevertheless, U.S. progress has been significant. In 1990 the United States
      mortality rate for men ranked ninth (a slight improvement) and for women 11th (no
      change).

PMID- 8266281
TI  - Selected health behaviors and perceptions among U.S. adults in 1990.
AB  - Risk factors for cardiovascular disease among Americans were analyzed using data
      from the 1990 Health Promotion and Disease Prevention supplemental survey to the
      annual National Health Interview Survey. Adult Americans were found to be quite
      heart-health conscious. More than half reported having had their cholesterol
      levels checked; of those with admitted hypertension, more than 85 percent said it
      was "under control" or "cured," and 44 percent of men and 37 percent of women
      exercised or played sports regularly. Just over 60 percent of men and 68 percent
      of women acknowledged "a lot" or "a moderate" amount of stress in their lives,
      and significantly more women than men considered themselves to be overweight.
      Variations in these perceptions and risk factors by age, sex, race, region and
      other socioeconomic variables are presented. The vast majority of the respondents
      reported "very good" to "excellent" general health, with proportionately more men
      than women in each age group reporting "excellent" health.

PMID- 8266282
TI  - Demographic trends from an economist's point of view.
AB  - Demographic shifts over time have significant impacts on labor markets,
      production and consumption patterns, saving and investment, and the overall
      growth of the economy. Among key shifts in the age composition of the population
      in the immediate future are slower growth of young workers and those in the key
      family formation ages, the movement of the baby boomers into their peak spending
      years and slower growth for prime saving ages. But the most dramatic changes of
      all will occur when the baby-boom generation begins retiring in large numbers in
      the second decade of the next century. This will require substantial investment
      in human and physical capital to facilitate the productivity gains needed to
      offset the surge in the old-age dependency ratio. Other important demographic
      trends from an economic point of view include the increase of nontraditional
      families and the huge variations in growth among various geographic areas.

PMID- 8266283
TI  - [Family therapy in Norway].

PMID- 8266284
TI  - [Blood vessel prostheses below the inguinal ligament--what shall we use?].

PMID- 8266285
TI  - [Transport of ill newborn infants].

PMID- 8266286
TI  - [Transport from a subregional neonatal unit. Experiences from Vestfold Central
      Hospital during an 11-year period 1982-92].
AB  - A key element of neonatal regionalization is the establishment of transport links
      between centres of tertiary care and subregional centres. During the 11-year
      period 1982-92, 186 transports were undertaken from the neonatal unit, Vestfold
      Central Hospital, for a total of 180 patients, or 0.8% of all live born infants
      (n = 23,652). 64 patients (36%) were referred for prematurity/respiratory
      distress syndrome (IRDS), 81 (45%) for congenital malformations, and 35 (19%) for
      other conditions. Transports for prematurity/IRDS declined significantly from the
      the first 6-year period 1982-87 to the last 5-year period 1988-92 (3.6 vs. 1.8
      per 1,000 live born infants; p < 0.01), owing to the establishment of a local
      respirator treatment programme for severe IRDS. In 71 (38%) transports the
      infants were mechanically ventilated. Seven (10%) suffered in-transport
      complications related to the endotracheal tube. At arrival, significantly more
      patients were anaemic (Hb < 14 g%; transports before 48 hours after birth),
      alcalotic (pH > 7.50), hypocapnic (PCO2 < 4 kPa) or had a base excess < -10
      mmol/l than before transportation (p < 0.05). There was a tendency towards more
      patients with hypothermia (tp < 36 degrees C), acidosis (pH (< 7.20) and
      hypercapnia (PCO2 > 10 kPa) at arrival than before transportation (p > 0.05). No
      deaths occurred during transport. However, two infants died within two hours
      after arrival, giving a transport-related mortality rate of 1%. Transporting
      critically ill neonates implies discontinuity of treatment and monitoring of
      these infants. Optimal stabilization before transportation, and scrupulous work
      on technical details are of utmost importance.

PMID- 8266287
TI  - [Autologous vein vs. human umbilical vein for femoropopliteal bypass].
AB  - Below knee femoropopliteal bypass was performed with reversed saphenous vein in
      81 cases and with modified human umbilical vein in 74. The two groups were
      comparable as regards indications, coexisting disease and distal run-off. The
      cumulated patency rates were almost identical in the two groups, but early
      mortality and wound complications were higher in the saphenous vein group.
      Aneurysm formation in the umbilical veins was not a problem in this series. It is
      concluded that human umbilical vein is a very satisfactory bypass alternative
      when the saphenous vein is not available. In selected cases it may also be
      justifiable to use it in order to keep operation time and trauma at a minimum.

PMID- 8266288
TI  - [Use of laboratory examinations in the organized occupational health services].
AB  - The extent of laboratory examinations in the health programmes of Norwegian
      companies was studied by questionnaire. From the reports (60% response) it can be
      calculated that less than 14% of the tests were requested to control employees at
      elevated occupational risk. Two thirds of the tests were carried out as part of
      programmes for screening of presumptive healthy individuals at no special risk.
      There were large variations in this service from company to company. About 75% of
      the analyses were performed at the occupational health service premises, usually
      by nurses without laboratory education. It is concluded that the use of
      laboratory examinations in occupational medicine should be critically evaluated.

PMID- 8266289
TI  - [Labor induction. Quality assurance of a method].
AB  - This paper presents a prospective study of all inductions of labour at a
      Norwegian obstetric department during 1992. The study was performed to assure the
      quality of the induction procedure. 323 labours (7.5%) out of a total of 4,289
      deliveries were induced. Hypertensive disorders were the most common indication
      for induction. The progress and outcome of the induced labours in women without
      prelabour rupture of membranes have been compared with equivalent data on
      spontaneous deliveries. The babies of 39 (12.6%) of 310 women in the induction
      group were delivered by Caesarean section, as against 13 (4.2%) in the
      spontaneous delivery group. Duration of labour is longest, and rate of operative
      deliveries is highest (48%), in nulliparous women with unripe cervix. The
      progress and outcome of labour are only slightly affected by the indication for
      induction and the gestational age.

PMID- 8266290
TI  - [Injuries in epileptic seizures].
AB  - The authors describe a prospective study on seizure-related injuries in Norway's
      two nursing homes for persons with epilepsy. 62 multihandicapped patients, most
      of them with a form of epilepsy that is difficult to treat, were assessed for 13
      months. A total of 6,889 seizures, 2,696 with ensuing falls, resulted in 80
      injuries. This gives a seizure-related injury risk of 1.2%. Only six serious
      injuries were recorded. The types of seizures most often causing the injuries
      were atonic and tonic-clonic seizures. Prophylactic measures are discussed. Since
      the risk of injury was found to be small, we conclude that even people with
      refractory epilepsy should be encouraged to live active lives.

PMID- 8266291
TI  - [Rectal prolapse. Experiences with rectopexy and Delorme's operation].
AB  - During the period 1982-91, 52 patients were treated for rectal prolapse. We
      present the results for 25 treated with Delorme's operation and 14 with
      rectopexy, all of whom were observed for more than 12 months after operation.
      Four patients who had internal prolapse were treated with rectopexy. Eight (15%)
      of 52 patients had postoperative complications, including six in the Delorme
      group and two in the rectopexy group. A 75 year-old woman operated with rectopexy
      died from peritonitis. Eight patients (32%) developed recurrent prolapse after
      Delorme's operation. Five of these were successfully reoperated. No patients in
      the rectopexy group had a recurrent prolapse. Incontinence and bleeding were
      reduced in both groups. Despite a relatively high rate of recurrence, we consider
      Delorme's operation to be a good alternative, also for old debilitated patients,
      and to involve a minimal risk of serious complications. If recurrence occurs,
      reoperation can be carried out with good results.

PMID- 8266292
TI  - [Benign fibrous mesothelioma of the pleura].
AB  - Benign fibrous mesothelioma of the pleura is rare. The tumour may present in
      several ways, as shown in our two patients, one with an elevated diaphragm and
      the other with slowly growing intrathoracic tumour. The tumour may reach a
      considerable size, is localized, is normally benign, and is curable by surgical
      resection.

PMID- 8266293
TI  - [Drowning--near drowning].
AB  - In Norway the number of deaths per year from drowning is approximately nine
      persons per 100,000, most of them men between 25 and 40 years of age. About 60%
      of these persons can swim, and 50% of the deaths are related to intake of
      alcohol. About 6% of the drowned are children, most of them boys. In disaster
      medicine, drowning is associated with accidents at sea, involving large vessels
      or small boats, or connected to offshore activities. The important pathological
      events are directly related to asphyxia, hypoxemia, hypercarbia, pulmonary
      oedema, and circulatory arrest. This paper describes various aspects of drowning
      and the pathophysiological processes involved, and discusses differences between
      drowning and near drowning in fresh water and salt water. Although treatment is
      basically centred on effective cardiopulmonary resuscitation, there are certain
      differences with regard to further treatment and fluid/electrolyte management.
      Hypothermia is often a prominent feature, and if cardiopulmonary resuscitation is
      successful, hypoxic brain damage may be ameliorated by the fall in body
      temperature.

PMID- 8266294
TI  - [Local frostbites].
AB  - Injury from cold is not an uncommon complication in emergency and disaster
      medicine under arctic or subarctic conditions. Severe local exposure to cold may
      have a mutilating effect on the parts of the body involved. This paper briefly
      summarizes relevant pathophysiological features, how cold injuries are
      classified, the most important clinical findings, complications and aspects of
      recommended treatment.

PMID- 8266295
TI  - [Genital mutilation of women. A new challenge for the health service].
AB  - Female circumcision, or genital mutilation is practised around the world. Because
      of war, conflicts and poverty, many women from cultures involving this practice
      now enter European communities. Some of them demand circumcision for their
      children. Genital mutilation of women has serious health effects, and in our
      societies there is a strong demand for its eradication. The cultural reasons for
      genital mutilation are varied, but it is not a compulsory part of the Islamic
      faith. Health workers in Norway may lack knowledge on how to handle these women
      when they meet them in their daily work. Sometimes unnecessary interventions are
      performed, sometimes ignorance may cause traumatic experiences for both patient
      and doctor. This article describes some of the social and cultural background for
      continued exposure to female mutilation, the health effects and some suggestions
      for interventions.

PMID- 8266296
TI  - [Infrared tympanic thermometry--worse than reported?].
AB  - A comparison of parallel measurements of body temperature with infrared tympanic
      thermometry (First Temp 2000A) in both ears and with rectal mercury thermometer
      were performed in 100 patients with stroke (n = 60) or spinal cord injury (n =
      40). Agreement between the two methods of temperature determination was assessed
      by calculating limits of agreement within which 95% (+/- 2 SD) of the individual
      differences would fall. Ear temperature was on average 0.3 +/- 1.0 (2 SD) degrees
      C above rectal temperature (p < 0.01). The upper and lower limits of agreement
      between the two methods were -0.7 degrees C and +1.3 degrees C, respectively.
      Mean difference between ear temperature in right and left ear was 0.0 +/- 0.7 (2
      SD) degrees C. According to these results tympanic membrane temperature measured
      with First Temp 2000A appears to give clinical significant erroneous readings,
      and should be used with caution.

PMID- 8266297
TI  - ["Outliers" in a surgical department. Experiences based on the DRG classification
      system].
AB  - According to the DRG classification system, 3% (201/6,954) of the patients
      treated in a 150-bed surgical department in 1991 were defined as outliers, i.e.
      their length of stay exceeded the upper limit of a "normal" stay as defined by
      the DRG system. These patients consumed 20% of total in-hospital days. In 16% of
      the outliers, hospitalization was extended because of advanced cancer. In 14% of
      the outliers the stay in hospital was prolonged because an out-patient social
      service could not be established or the patient could not be transferred to a
      nursing home. In 35% of the outliers, the disease itself was responsible for the
      extended stay. Complications following treatment were the cause of prolonged stay
      in hospital in 35% of the outliers.

PMID- 8266298
TI  - [Adenocarcinoid of the appendix vermiformis].

PMID- 8266300
TI  - [Lobotomy--a distorted picture of psychiatric treatment].

PMID- 8266299
TI  - [EDTA treatment in patients with atherosclerotic diseases].

PMID- 8266301
TI  - [More about thick oversocks].

PMID- 8266302
TI  - [Cesarean section in rural communities].

PMID- 8266303
TI  - [Care is not a health service].

PMID- 8266304
TI  - [Ethical guidelines on medical research involving children].

PMID- 8266305
TI  - [The effect of 3 times per year random vaccination of sows against Aujeszky's
      disease on maternal immunity in a breeding farm].
AB  - Research was undertaken to study the effect of a 'three times a year vaccination
      schedule in sows' against Aujeszky's disease (AD) on the maternal immunity of
      their offspring at a large pig farm. Only gI-negative sows and piglets were
      induced in the study. The maternal immunity was measured in the 8-week-old
      offspring of 6 gilts and 13 sows, vaccinated in early pregnancy and in 8-week-old
      piglets born from 12 gilts and 21 sows vaccinated 3 weeks prior to farrowing. At
      an age of 8 weeks only 5 percent of the piglets, born from sows vaccinated during
      early pregnancy showed antibody titres against AD of > 1:40 in their serum. In
      piglets born from sows vaccinated 3 weeks prior to farrowing more than 50 (54.4)
      percent of the piglets showed antibody titres > 1:40 in their serum. It was
      concluded that using a 'three times a year vaccination schedule' in a gI negative
      herd may lead to groups of seronegative piglets on breeding and multiplier farms.
      The implications are discussed.

PMID- 8266306
TI  - [Infectious diarrhea of calves: therapeutic and preventive possibilities based on
      etiological, pathophysiological and immunological data].
AB  - In this article the current knowledge on the development mechanisms of bacterial,
      viral and cryptosporidial neonatal calf diarrhoea are briefly reviewed as basis
      for an efficacious prophylaxis strategy. Hygienic measures will prevent the
      infection of the calf before colostrum intake and will diminish the infection
      pressure during the first weeks of life. Moreover, local intestinal immunity will
      be provided by early administration of immune colostrum for the prevention of
      E.coli diarrhoea and prolonged administration of colostrum or immune milk during
      the first weeks can protect against viral diarrhoea. To obtain a maximum level of
      E.coli antibodies in colostrum, the last vaccination has to be administered at
      least 8 weeks before parturition. Prolonged excretion of antiviral antibodies in
      the milk for several weeks, can be achieved by a 'priming' vaccination with an
      adjuvanted inactivated vaccine during pregnancy, followed by a booster
      vaccination within 24 hours after parturition. Cryptosporidium parvum diarrhoea
      can be prevented with halofuginone lactate.

PMID- 8266307
TI  - [The registration of veterinary drugs in The Netherlands].
AB  - An overview is given of the organisation and working procedures of the evaluation
      of veterinary medicines in the Netherlands. The results of the evaluation
      procedure of the last 5 years are discussed together with the problems that have
      arose for authorities and industry. An overview is also given of the problems
      that have to be tackled in the near future.

PMID- 8266308
TI  - [Improved diagnosis via anamnesis and roentgen pictures].

PMID- 8266309
TI  - [Prevention and control of round worms].

PMID- 8266310
TI  - [Problems with record keeping].

PMID- 8266312
TI  - [Congenital complete atrioventricular block in neonatal lupus erythematosus].
AB  - Fetal bradycardia of 60 beats per minute was diagnosed in the 22nd week of a
      normal pregnancy. Echocardiography showed a complete fetal atrioventricular heart
      block. The fetal heart was without structural abnormalities. Auto-antibodies
      (Ro/SS-A and antinuclear antibodies) could be demonstrated in both mother and
      child. The mother, however, showed no signs or symptoms of a connective tissue
      disease. We describe neonatal lupus erythematosus as an important cause of
      congenital heart block.

PMID- 8266311
TI  - [Breast feeding and oral anticoagulants].
AB  - Oral anticoagulants are frequently prescribed during lactation. Because these
      drugs could affect the hemostasis of the newborn, we did a literature search to
      find out whether precautions should be taken. It appeared that acenocoumarol and
      warfarin are not detectable in human milk. Besides the usual daily
      supplementation of 25 micrograms vitamin K for every breast-fed infant,
      precautions are not necessary. Phenprocoumon, ethylbiscoumacetate and phenindione
      are excreted in human milk and could affect neonatal hemostasis.

PMID- 8266313
TI  - [Visceral leishmaniasis: a possible diagnosis in Belgium].
AB  - A 22-months old girl contracted visceral leishmaniasis during a vacation in
      Portugal, 12 months prior the manifestation of disease. She presented with fever,
      hepatosplenomegaly and pancytopenia. A serological test proved the diagnosis.
      Therapy with a pentavalent antimony drug brought about immediate improvement.
      Visceral leishmaniasis has to be suspected in individuals with fever,
      hepatosplenomegaly and pancytopenia who have resided in endemic areas
      (Mediterranean countries, India, East Africa, South America) during the previous
      years. If untreated, visceral leishmaniasis runs a fatal course. Therefore, early
      diagnosis by morphological and serological means and specific therapy with
      pentavalent antimony drugs are mandatory.

PMID- 8266314
TI  - [Hemoptysis as manifestation of a Helicobacter pylori infection].
AB  - A 14-year-old girl was transferred to our unit after 6 weeks of repeating
      episodes of what was thought to be 'hemoptysis'. Apart from discrete nausea, she
      did not have any other complaints. The episodes of 'hemoptysis' occurred once
      every 3 days, mostly in the late evening. The physical examination was strictly
      normal. A thorough investigation revealed a chronic active gastritis and
      Helicobacter pylori infection. No lung disease could be confirmed. Treatment
      consisted of a combination therapy with amoxycillin (50 mg/kg/day orally in 3
      doses) and colloidal bismuth subcitrate (120 mg orally, 3 times daily) during a
      period of 1 week. Together with the clearance of Helicobacter pylori and healing
      of the chronic active gastritis, as demonstrated by histology, the symptoms
      disappeared. An eradication of the microorganism was obtained. Since that time,
      she has had no further similar complaints. This case reflects an atypical
      presentation of Helicobacter pylori infection.

PMID- 8266315
TI  - [Late diagnosis of classical galactosemia. An adult with special biochemistry].
AB  - The atypical case history of a galactosemic patient who was not recognized as
      such until his 22nd year is described. As in classical galactosemia there was not
      found any galactose-1-phosphate uridyl transferase activity in the erythrocytes.
      However, after the patient was on a galactose-free diet, there was no
      demonstrable elevation of galactose-1-phosphate in the erythrocytes. We would
      advocate a limited screening on galactosemia.

PMID- 8266316
TI  - [Intrauterine invagination in a newborn infant].
AB  - Intussusception in neonates is rare. We present a case of neonatal intrauterine
      intussusception, which was treated by partial colectomy. Differences between
      neonatal and infantile intussusception are detailed. Because of the advanced
      clinical signs of intestinal obstruction and the increased risk of perforation
      when hydrostatic reduction is performed, operative reduction and/or resection is
      recommended.

PMID- 8266317
TI  - [A child with Chlamydia trachomatis pneumonia].
AB  - A six week old boy is presented with a Chlamydia trachomatis pneumonia. This
      pneumonia is seldom diagnosed because of the mild clinical symptoms and the good
      prognosis, even without therapy. Diagnosing the Chlamydia trachomatis infection
      of the neonate is of importance for the mother and the child. Chlamydia
      trachomatis infections in neonates are an underestimated problem.

PMID- 8266318
TI  - A monoclonal antibody with specificity to the HLA-DR1 and -DR51 antigens.
AB  - A monoclonal antibody 137BL7 raised against purified DR1 protein was shown to
      bind specifically to 5/5 DR1, 18/18 DR2 cells and 0/23 non-DR1,2 cells by cell
      EIA. Further analysis by FACS using HLA-transfectants revealed that 137BL7 also
      bound specifically to the DRB5 transfectants in addition to the expected DR1
      transfectants. However, it did not bind to the DR2 (DR15) transfectants, showing
      that cross-reactivity with DR2 cells lies with the DRB5 (DR51) rather than the
      DRB1 gene product. A comparison of the HLA-DR amino acid sequences of DR1 and
      DR51 antigens revealed a common glutamic acid residue at position 96, which may
      form the putative binding epitope of this mAb.

PMID- 8266319
TI  - Major histocompatibility complex class II haplotypes in a breeding colony of
      chimpanzees (Pan troglodytes).

PMID- 8266320
TI  - Quantitation and characterization of plasma HLA in neonates of different
      gestational ages.
AB  - The functional significance of plasma HLA class I antigens is unclear. They are
      thought to have an immunomodulatory role and be tolerogenic in transplant
      settings including the materno-fetal semi-allograft. There is, however, no
      available data on the concentrations of soluble HLA class I antigens in fetuses
      or newborns. We therefore determined plasma HLA class I antigen levels in 93
      neonates born at different gestational ages and compared them to those in 66
      healthy adults. The mean plasma HLA concentration in cord blood obtained from
      these neonates (0.30 +/- 0.15 microgram/ml, mean +/- SD) was significantly lower
      (p < 0.0001) than in the adults (0.77 +/- 0.44 microgram/ml). No correlation
      between the plasma HLA levels and the gestational ages of the neonates was
      detected. Characterizing the plasma HLA class I antigens by immunoprecipitation
      and immunoblotting, four different molecular weight forms, 44, 39, 36 and 34 kDa,
      were recognized. Their distribution in neonates was not different from that in
      adults. Since the circulating leukocytes are a probable source of plasma HLA
      class I antigens, we measured the surface HLA expression on leukocytes in 4
      neonates and 4 adults by immunofluorescent flow cytometry. The fluorescence
      intensities on neonatal granulocytes and lymphocytes were 50% of those on
      corresponding adult cells. This finding suggests that the reduced HLA expression
      by neonatal leukocytes may be partially responsible for the lower concentration
      of HLA class I antigens in neonatal plasma.

PMID- 8266322
TI  - Defining the common subtypes of HLA A9, A10, A28 and A19 by use of ARMS/PCR.
AB  - We describe sequence-specific primer (SSP) combinations for use in a one-step
      polymerase chain reaction (PCR) typing system to determine HLA-A locus subtypes
      of A9 (A23, A24), A10 (A25, A26, A43), A28 (A*6801, A*6802, A*6901) and A19
      (A*2901, A*2902, A*3001, A*3002, A31, A32, A33) from genomic DNA. SSP's were
      designed on the basis of the amplification refractory mutation system (ARMS) in
      which a mismatch at the 3' residue inhibits non-specific amplification. The SSP
      combinations described extend our low-resolution typing system, to provide a high
      definition typing of the HLA-A locus.

PMID- 8266321
TI  - DNA-binding proteins for transcription enhancing region of HLA class I gene.
AB  - Class I regulatory complex (CRC) located in the 5'-upstream region of MHC class I
      gene contains transcriptional enhancing sequences, called Enh A. This Enh A
      region contains tandem-arranged kappa B-like sites, one of which has a well
      conserved perfect palindromic sequence. The second kappa B-like site, juxtaposed
      to the perfect palindrome, contains an imperfect palindromic sequence. In B-cell
      nuclear extracts, we have identified at least four sequence-specific protein
      complexes; three shared the repeated kappa B enhancer as their binding motifs.
      The perfect palindromic sequence facilities the binding of a complex termed BI,
      while the imperfect palindrome provides the binding sites for two other
      complexes, BII and BIII. The BII and BIII complexes exhibited binding
      crossreactivity with other kappa B-related motifs and recognized both the perfect
      and imperfect palindromic sequences, whereas the BI complex was specific for the
      perfect palindromic sequence which is unique to the class I promoters. A DNA
      segment outside the repeated kappa B enhancers probably binds the fourth complex,
      BIV. These complexes, except for the perfect palindrome-binding complex, differ
      from those described for the murine class I promoter. The binding characteristics
      of these factors suggest that the mechanism controlling the class I transcription
      may be quite complex.

PMID- 8266323
TI  - The effect of acupuncture stimulation of the middle latency auditory evoked
      potential.
AB  - The effects of acupuncture stimulation (AS) on the middle latency auditory evoked
      potentials (MLAEPs) were studied in 19 normal male volunteers. Scalp recordings
      were made from 21 points (including Cz) and posterior auricular muscle (PAM)
      electrodes referenced to the linked mastoid. Four components of MLAEPs (Po, Na,
      Pa and Nb) and two components of PAM reflex (N12 and P17) were statistically
      analyzed for changes in latency and amplitude. Wave phase of Po and Na reversed
      to N12 and P17, respectively, and the peak-to-peak amplitude of Po-Na, Na-Pa, Pa
      Nb and N12-P17 showed a marked increase during AS to the ipsilateral side whereas
      no change in latency was detected. Each component's isovoltage topographic maps
      and dipole locations were calculated to be near both PAM (Po and Na) and temporal
      positions (Pa and Nb) during AS. These data showed that AS can promote MLAEPs
      activity and these signals (Po and Na) may originate from increased activity in
      N12 and P17 of the PAM reflex, respectively, and that the auditory cortex of the
      temporal gyrus is the generator substrate of Pa and Nb.

PMID- 8266324
TI  - Prevalence of serum IgG antibodies for the E7 and L2 proteins of human
      papillomavirus type 16 in cervical cancer patients and controls.
AB  - Relationship between the prevalence of the antibodies to HPV16E7 and L2 proteins
      and the development of cervical cancer was examined. Sera from 57 patients with
      invasive cervical cancer and from 200 age-matched healthy blood donors (16 to 64
      years old) were examined for antibodies against E7 and L2 proteins of human
      papillomavirus (HPV) type 16. Bacterially expressed fusion antigens were used in
      a Western immunoblot assay. Ten (18%) of the patients and 10 (5%) of the controls
      were positive for only E7. Each eighteen of the patients (32%) and of the
      controls (9%) were positive for only L2. Three of the patients and 2 of the
      controls were positive for both E7 and L2 antibody reactivity. The patients'
      prevalence of antibodies for the E7 and L2 proteins was significantly higher than
      that of the controls (E7: chi 2 = 14.3, p < 0.01; L2: chi 2 = 23.8, p < 0.01). On
      the other hand, neither sex specific difference in the antibody prevalence was
      observed, nor was there any difference in the antibody prevalence with age. Our
      findings indicate that antibodies to the HPV16L2 proteins could be a parameter
      for cervical cancer development as well as those to the HPV16E7 proteins.

PMID- 8266325
TI  - Evaluation of diagnostic assays for neonatal and infantile chlamydial infections.
AB  - Several diagnostic assays for neonatal and infantile chlamydial infections,
      isolation with tissue culture, antigen detection by enzyme immunoassay (EIA)
      (IDEIA Chlamydia test), a nonisotopic DNA probe (Gen-Probe PACE 2 assay), serum
      IgM antibody detection by EIA (SeroELISA Chlamydia TRUE IgM), and polymerase
      chain reaction (PCR), were evaluated. Of 210 clinical specimens (170
      nasopharyngeal and 40 conjunctival swabs) from 53 neonates and 102 infants with
      respiratory insufficiency and respiratory tract infections which were suspected
      to be associated chlamydial infection, chlamydial antigens were detected in 30 by
      IDEIA Chlamydia. Of these 30 samples, C. trachomatis was isolated from 27
      specimens. Samples from 15 neonates and 6 infants were culture-positive and IDEIA
      Chlamydia-positive. Of 30 samples, 27 were tested with PCR and 8 with DNA probe.
      Twenty-three of 27 specimens were positive with PCR, while only one specimen was
      positive with DNA probe. EIA can be used for the diagnosis and screening of
      neonatal and infantile chlamydial infections.

PMID- 8266326
TI  - Some features in prostaglandin synthesis of the cancer cells which metastasized
      into liver from intestinal cancer lesions.
AB  - In order to study the mechanism of cancer metastasis, AH100B cells, an ascitic
      hepatoma cell line, were transplanted into the small intestine of male Donryu
      rats. Each metastatic nodule in the liver was collected with the respective
      intestinal lesion. Each sample thus obtained was injected into the peritoneal
      cavity of male Donryu rats to make free cancer cells. Then, the cancer cells,
      having an intact cell surface, of the metastatic and primary intestinal lesion
      were collected respectively. After washing in Dolbecco's PBS (Ca2+ and Mg(2+)
      free, pH 7.2), the definite numbers of cancer cells of the metastatic and primary
      intestinal lesion were incubated in the PBS containing [1-14C]-AA at 25 degrees C
      for 30 min, respectively. AA metabolites formed during the incubation period were
      extracted and subjected to TLC, followed by autoradiography. Each radioactive
      part was scraped off the plate and measured for its radioactivity. The pattern of
      the ability to synthesize PGs was different between the cancer cells which
      metastasized to the liver and those of the primary lesion, that is, percentage
      values of PGE2 and PGF2 alpha were higher (p < 0.01) in the cancer cells which
      metastasized to liver as compared with those of the primary intestinal lesion.
      These results suggest that PGs produced by hepatic metastatic cancer cells might
      play an important role in cancer metastasis.

PMID- 8266327
TI  - Sister chromatid exchanges in mouse after exposure to pulse-wave ultrasound in
      utero.
AB  - The induction of sister chromatid exchanges (SCEs) was investigated in mice after
      a ten min exposure, in vivo, to 2 MHz focused, pulse-wave ultrasound with a pulse
      repetition rate of 1000 Hz, pulse duration of 10 microseconds. The bone marrow
      cells of the pregnant female mice and the fetal liver cells were analyzed. The
      cell cycle specific metaphase patterns were additionally evaluated. In the bone
      marrow cells, the mean frequencies of SCEs were 2.77 in control, 3.56 in the
      cells exposed to ultrasound at 586.2 mW/cm2 (spatial average temporal average,
      SATA); in the fetal liver cells, 2.64 in control, 3.84 in the cells exposed. The
      frequencies of SCEs significantly were increased by the treatment. Faster cell
      kinetics was observed in fetal liver cells than bone marrow cells of pregnant
      female. But there was no cell-growth inhibitory effect of ultrasound on both bone
      marrow and fetal liver cells. In fetal liver cells, the critical acoustic power
      was 160.0-278.9 mW/cm2 (SATA).

PMID- 8266328
TI  - High Epstein-Barr virus (EBV) susceptibility of both lymphoblastoid and lymphoma
      cell lines derived from a Japanese patient with EBV genome-positive Burkitt's
      lymphoma.
AB  - A Lymphoma cell line from the tumor tissue was established spontaneously from a
      Japanese patient with Epstein-Barr virus (EBV) genome-positive Burkitt's lymphoma
      (BL). Additionally lymphoblastoid cell lines from peripheral blood of this
      patient were established either spontaneously or by in vitro infection with B95-8
      EBV. Lymphoma cells showed monoclonal surface immunoglobulins (kappa and gamma)
      with specific chromosomal translocations, t (8; 14). In contrast, lymphoblastoid
      cells expressed polyclonal surface immunoglobulins without specific chromosomal
      abnormalities. Lymphoma cells made colonies in soft agarose approximately 10
      times more than those of the lymphoblastoid cells. When each cell line was
      cultured at lower temperature of 33 degrees C, treated with 12-O-tetradecanoyl-
      phorbol-13-acetate (TPA), and superinfected with P3HR-1 EBV, all cell lines
      expressed 5 to 10 times higher levels of EBV early antigens (EA) and viral capsid
      antigen (VCA) than lymphoblastoid cell lines from healthy controls. Furthermore,
      lymphoblastoid cell lines obtained from peripheral blood of this patient during
      the period of remission also exhibited high EA and VCA inducibility and
      superinfectibility. These findings suggested that the lymphoid cells in this
      patient were genetically highly susceptible to EBV infection, and this evidence
      possibly linked to the lymphomagenesis of EBV genome-positive BL.

PMID- 8266329
TI  - Lectin binding in bone matrix of adult rats with special reference to cement
      lines.
AB  - The present study was designed to localize glycoconjugates recognized by four
      lectins (LFA, MPA, WGA, and ConA) in adult rat bone, histochemically and
      biochemically. LFA, a lectin recognizing sialic acid, stained intensely the
      cement lines of calvariae and the interface between cartilage and bone of
      mandibular condyles, which were also stained with WGA, and intermittently stained
      with ConA. The irregular bone surface of calvariae displayed intense positive
      reaction with LFA and WGA, while the osteoid of mandibular condyles and the
      smooth bone surface of calvariae were intensely stained with WGA and ConA, but
      weakly stained with LFA and MPA. MPA recognized osteoclasts. At the superficial
      layer of mandibular condyles, the bone matrix appeared positive as granules with
      LFA and as patches with MPA, WGA and ConA. Lectin blotting analysis of bone
      extracts revealed two LFA positive bands at molecular weights of 18 kDa and 45
      kDa. The former was positive with WGA, ConA, and MPA, while the latter was
      positive with MPA. The result suggests that the LFA-binding glycoconjugates,
      possibly 18 kDa and/or 45 kDa sialoglycoconjugates, may contribute to cementing
      mechanism of cement lines and/or to the bone formation in remodeling process as
      well as in intramembranous and intracartilaginous osteogenesis.

PMID- 8266330
TI  - An experimental study on the objective measurement of accommodative amplitude
      under binocular and natural viewing conditions.
AB  - A high resolution optometer makes it possible to measure changes in refractive
      power objectively using reflected light from the fundus of the eye. There are
      limitations in that the subject has to see the target monocularly through a hole
      in the instrument. In the present study, we attempted to measure the
      accommodation and pupillary response with a newly developed device as a means to
      measure these factors in both binocular and natural viewing conditions. We
      compared the subjective accommodative amplitude levels obtained from the near
      point distance with those of objective accommodative amplitude obtained in
      earlier studies using a monocular internal target. The amplitude of accommodation
      of the cases with binocular, natural viewing conditions was approximately 0.7 D
      larger than with monocular, internal target gazing. In previous studies, the
      difference between the subjective amplitude of accommodation and the results of
      the objective measurements, had been reported to be approximately 2 D, and was
      explained by the depth of focus. However, the difference between the subjective
      and objective amplitude of accommodation under binocular, natural viewing was
      smaller than that between the subjective and objective measurements (under
      monocular internal target gazing) from previous studies. This leads us to believe
      that besides the depth of the focus, we should consider the fact that the
      advantageous conditions inherent in binocular, natural viewing may increase the
      amplitude of accommodation. In the measurement of accommodative amplitude, the
      use of objective measuring methods are not affected by the subjects' subjective
      judgement.

PMID- 8266331
TI  - Food-borne heterocyclic amines. Chemistry, formation, occurrence and biological
      activities. A literature review.
AB  - This review summarizes the abundant literature on food-borne heterocyclic amines,
      their chemistry and formation, their occurrence in food, their biological
      activities including mutagenicity, induction of DNA damage and carcinogenicity.
      Pharmacokinetics and biotransformation are also discussed. Factors that influence
      these effects are given consideration, with special emphasis on dietary factors
      that might counteract detrimental biological effects. The annual per capita
      intake of heterocyclic amines via food is estimated. Risk extrapolations that
      have been published suggest that food-borne heterocyclic amines are relevant for
      human cancer etiology.

PMID- 8266332
TI  - Lung deposition, lung clearance and renal accumulation of inhaled cadmium
      chloride and cadmium sulphide in rats.
AB  - Rats were exposed 6 h/day over 10 days to 0.3 mg/m3 of water soluble cadmium
      chloride and 0.2, 1.0 and 8.0 mg/m3 of insoluble cadmium sulphide, then killed at
      intervals over a 3-month period for serial measurements of lung, renal and faecal
      cadmium. CdCl2 and high-dose CdS animals showed a transient increase in lung
      weight. Clearance of both compounds was biphasic. Approximately 40% of deposited
      material was cleared during the 10-day exposure period. For CdCl2, only 9% of the
      lung burden was cleared rapidly after the last exposure (half-life 1.0 days) and
      47% slowly (half-life 87 days), leaving a residual lung burden of 44%. For CdS,
      41% of the lung burden was cleared rapidly (half-life 1.4 days) and 40% slowly
      (half-life 42 days), leaving a final residue 19%. In the CdS high-dose group, the
      retention of CdS in the lung was greater than that in the CdS low-dose groups,
      indicating that clearance mechanisms may possibly have been impaired in the high
      dose group by too great a lung burden. For both compounds, faecal cadmium was
      initially high. Renal accumulation of cadmium was substantial for CdCl2 during
      the exposure period and continued over the following months until it represented
      approximately 35% of the total cadmium cleared from the lung. For CdS, renal
      accumulation was only 1% of the amount cleared from the lung. The bioavailability
      of Cd from CdS is thus poor, the majority being cleared from the lungs and
      excreted in the faeces. However, the bioavailability of inhaled CdS measured as
      cadmium in the kidney is greater than the bioavailability of orally ingested CdS.

PMID- 8266333
TI  - The penetration of 2,3,7,8-tetrachlorodibenzo-p-dioxin into viable and non-viable
      porcine skin in vitro.
AB  - Freshly harvested, full thickness porcine skin was kept metabolically viable at 4
      degrees C in a minimal essential medium for at least 48 h, as judged by the
      formation of lactate or 14CO2 from 14C-labeled glucose. In vitro topical exposure
      to the environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 65
      ng/cm2) for up to 1000 min did not affect the viability of skin. The penetration
      and distribution of TCDD into porcine skin was studied in an in vitro system
      under a variety of conditions, such as viability status, different vehicles or
      concentrations, or artificial removal of the stratum corneum. Loss of viability
      of the skin increased the rate of penetration of TCDD by about 60%. Removal of
      the stratum corneum to mimic lesioned skin increased the rate of dermal
      penetration of TCDD about 3-fold. The use of acetone as the vehicle, simulating
      dermal exposure to TCDD as a dust or from a volatile solvent, resulted in higher
      rates of penetration than the use of mineral oil as the vehicle, which simulates
      the situation of industrial accidents. The percentage of dose absorbed was
      independent of the dose of TCDD (65 or 6.5 ng/cm2) administered to the surface of
      skin. Rates of dermal penetration of TCDD ranged form 14 to 985 pg/cm2 skin per
      h, or 0.2-1.5% of the dose/h, depending on the conditions of exposure. These
      rates of penetration are comparable with results obtained by others in several
      other species, with both in vitro and in vivo systems including human skin in
      vitro. Full thickness porcine skin, viable or previously frozen, is therefore a
      valid in vitro model to estimate dermal penetration of TCDD in humans.

PMID- 8266334
TI  - Effect of microsomal enzyme modulators on N-(3,5-dichlorophenyl)-2
      hydroxysuccinimide (NDHS)-induced nephrotoxicity in the Fischer 344 rat.
AB  - We have previously reported that phenobarbital (PB) pretreatment enhances and
      piperonyl butoxide (PIBX) pretreatment or cobalt chloride (CoCl2) pretreatment
      decreases the nephrotoxicity induced by the model nephrotoxicant N-(3,5
      dichlorophenyl)succinimide (NDPS) in the Fischer 344 rat. The objective of this
      study was to determine the effect of a microsomal enzyme inducer (PB) or
      microsomal enzyme inhibitor (PIBX or CoCl2) on a single intraperitoneal (i.p.)
      injection of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS, 0.05, 0.1 or 0.2
      mmol/kg), a nephrotoxicant metabolite of NDPS, or vehicle (sesame oil, 2.5
      ml/kg). Renal function was monitored at 24 and 48 h post-NDHS for PB pretreated
      rats and at 24 h only for PIBX and CoCl2 pretreated rats, due to lethality at 48
      h in PIBX pretreated rats. PB pretreatment potentiated the renal toxicity induced
      by a non-toxic dose of NDHS (0.05 mmol/kg), inducing diuresis and elevated
      proteinuria, hematuria, glucosuria, blood urea nitrogen (BUN) concentration and
      kidney weight. PB pretreatment also enhanced some monitored renal effects of a
      toxic dose (0.1 mmol/kg) of NDHS, including reduced organic ion transport by
      renal cortical slices. PIBX and CoCl2 pretreatments did not markedly affect the
      increased kidney weight, proteinuria, glucosuria, BUN concentration or altered
      organic ion transport induced by NDHS (0.2 mmol/kg) treatment. We conclude that
      PB potentiates NDHS-induced nephrotoxicity via a mechanism not influenced by
      CoCl2 or PIBX.

PMID- 8266335
TI  - Glutathione depletion in human erythrocytes as an indicator for microsomal
      activation of cyclophosphamide and 3-hydroxyacetanilide.
AB  - A model system for the detection of reactive metabolites, using glutathione
      depletion after microsomal activation, has been described previously. We
      developed a battery of complementary test systems using rat liver microsomes for
      metabolism and aqueous glutathione solutions, human erythrocytes or hemolysate
      derived therefrom, as target. Reactive metabolite formation and the ability of
      metabolites to pass the erythrocyte membrane were tested using 3
      hydroxyacetanilide (3-HAA) and cyclophosphamide (CP) as substrates. Neither
      unchanged 3-HAA nor CP depleted glutathione in erythrocytes or in aqueous reduced
      glutathione solutions (GSH solutions). Addition of fortified normal or liver
      microsomes from rats pretreated with phenobarbital (PB microsomes) induced a 3
      HAA/CP concentration-dependent glutathione depletion in both systems. With PB
      microsomes, higher depletions were found. While unchanged 3-HAA did not deplete
      aqueous GSH solutions or glutathione in erythrocytes, a significant depletion in
      hemolysate was found. The results indicate that both CP and 3-HAA metabolites are
      able to pass through the erythrocyte membrane. While both substances can
      metabolically be activated by rat liver microsomes, only 3-HAA can be activated
      by soluble factors in erythrocytes. However, unchanged 3-HAA has no effect on GSH
      in erythrocytes. This might be caused by an inability of unchanged 3-HAA to enter
      the erythrocyte. More generally, an adequate combination of the test systems
      described can be used to detect (a) the reactivity of unchanged substances and
      their metabolites, and (b) the ability of unchanged substances and their reactive
      metabolites to pass through the erythrocyte membrane.

PMID- 8266336
TI  - Hepatotoxicity of piperonyl butoxide in male F344 rats.
AB  - Male F344 rats were given 0, 0.6, 1.2 or 2.4% of piperonyl butoxide in the diet.
      At 1, 2, 4 or 12 weeks after the beginning of the experiment, liver and kidney
      weight and serum clinical parameters were determined and livers and kidneys were
      examined with light microscopy. From 1 or 2-12 weeks, distinct increase of liver
      weight, changes in serum clinical parameters for liver damage, oval cell
      proliferation, bile duct hyperplasia, single cell necrosis, enlarged and
      vacuolated hepatocytes, enlarged nuclei and anisonucleosis were seen in treated
      rats. From 4-12 weeks, cell infiltration, focal necrosis, multinucleated
      hepatocytes and prominent nucleoli of hepatocytes were seen in treated rats. At
      12 weeks microgranulomas were seen in treated rats. Especially in rats of the
      2.4% group at 12 weeks, severe enlargement of hepatocytes, severe enlargement of
      nuclei and multinucleated hepatocyte were seen, suggesting preneoplastic
      alteration. Relative kidney weights and serum urea nitrogen levels were increased
      in treated rats from 1 or 2-12 weeks and at 12 weeks, atrophy of proximal
      tubules, dilation of tubules, cell infiltration, fibrosis and accumulation of
      yellow-brown pigment in the proximal tubular cells were seen.

PMID- 8266337
TI  - Pathogenesis of 2,2'-dichlorodiethyl sulfide in hairless guinea pigs.
AB  - Developing skin lesions on hairless guinea pigs due to 2,2'-dichlorodiethyl
      sulfide (sulfur mustard, HD) exposure were examined to determine the time course
      for the appearance of histopathologic markers in relationship to skin NAD+ and
      NADP+ content after HD exposure. Hairless guinea pig skin was exposed to HD for 8
      min by means of a vapor cup. Skin punches were taken at 1, 2, 4, 8, 12, 16, 20
      and 24 h after HD exposure. Intracellular edema (IE) appeared at 2 h and
      increased steadily over 24 h. Epidermal necrosis (EN) and pustular epidermatitis
      (PE) developed at 8 h and reached a maximum at 16 h. Follicular necrosis (FN)
      appeared at 8 h and increased up to 24 h. Microvesicles (MV) developed between 12
      16 h reaching a maximum at 24 h. Niacinamide (750 mg/kg, ip) pretreatment (30
      min) reduced the incidence of MV (40%) and FN (45%) at 24 h, but did not reduce
      IE, EN, or PE. In all animals, skin NAD+ content decreased to a minimum (20% of
      control) at 16 h, but NAD+ decreases did not precede microvesicle formation. Skin
      NADP+ content increased (260%) between 1-2 h and returned to control at 4 h. Skin
      cell NADP+ increases may be indicative of an early phase of cellular oxidative
      stress that may contribute to HD-induced dermal pathogenesis. Since NAD+
      reductions did not precede microvesication and NAM-induced increases in NAD+
      content did not delay or reduce early cellular alterations, the contributory role
      of NAD+ to microvesicle formation may be limited and other biochemical changes
      should be investigated.

PMID- 8266338
TI  - Effects of 2-[1-(ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex
      2-enone on hepatic haem biosynthesis: species differences in hepatic porphyria.
AB  - 2-[1-(Ethoxyimino)propyl]-3-hydroxy-5-(2,4,6-trimethylphenyl) cyclohex-2-enone
      (ETC) is a novel alkyl ketone herbicide. Continuous administration of ETC to mice
      for 28 days resulted in marked liver enlargement and severe intrahepatic
      cholestasis. These effects have been shown to result directly from a rapid and
      marked accumulation of porphyrin in the liver. The porphyrin which accumulates in
      the liver has been identified as protoporphyrin IX and dose response and time
      course studies confirm prior inhibition of mitochondrial ferrochelatase as the
      causal lesion. ETC was a very potent porphyrinogenic compound in mice, with a no
      effect level for a single oral dose of 1 mg/kg. Rats and hamsters were
      insensitive to this type of hepatotoxicity following single oral doses of up to
      750 mg/kg or following repeated, and indeed prolonged administration. The
      sensitivity of different species to ETC-induced porphyria correlated with the
      effect of ETC on hepatic ferrochelatase activity. The inhibition of
      ferrochelatase activity and the hepatic porphyria in mice were both found to be
      readily reversible upon withdrawal of ETC.

PMID- 8266339
TI  - Chlorate poisoning: mechanism of toxicity.
AB  - Intoxications with chlorate salts are characterized by methaemoglobin formation,
      haemolysis and renal insufficiency. The toxic effects on the erythrocyte can be
      reproduced in vitro. Incubation of human and rabbit erythrocytes with chlorates
      induces a concentration-dependent oxidation of haemoglobin. This methaemoglobin
      formation is followed by denaturation of the globin, a cross-linking of
      erythrocyte membrane proteins and an inactivation of membrane enzymes. The high
      sensitivity of glucose-6-phosphate dehydrogenase to denaturation by chlorate
      explains the inefficacy of methylene blue to reduce methaemoglobin formed, as the
      antidotal effect of methylene blue depends on NADPH formed mainly by the
      oxidation of glucose-6-phosphate. The observed changes occur only in the presence
      of methaemoglobin which forms a destabilising complex with chlorate.
      Methaemoglobin thus autocatalytically increases methaemoglobin formation and
      destruction of the erythrocyte. As the rabbit is known to have a high
      methaemoglobin-reduction capacity, human and rabbit erythrocytes were compared.
      In vitro, the rabbit erythrocyte is less sensitive to oxidative attack than the
      human red cell. In vivo, an oral dose of sodium chlorate (1 g/kg body wt.)
      resulted in high serum (16 +/- 4 mM) and urine concentrations (246 +/- 99 mM) in
      the rabbit. Methaemoglobin was not formed nor could a nephrotoxic effect be
      observed. These experiments also indicate that the nephrotoxicity of chlorate is
      mediated by methaemoglobin catalysis.

PMID- 8266340
TI  - Effects of 20 months of ozone exposure on lung collagen in Fischer 344 rats.
AB  - Fischer 344 rats were exposed to filtered air (controls) or to 0.12, 0.5, or 1.0
      ppm of ozone for 6 h/day, 5 days/week, for 20 months. We examined lung collagen
      deposition and metabolism in tissue from these animals to determine whether
      chronic exposure of rats to ozone causes pulmonary fibrosis. We observed excess
      stainable collagen in the centriacinar region of lungs from the rats exposed to
      0.5 or 1.0 ppm of ozone. Biochemical analysis indicated a slight, yet
      significant, excess collagen deposition in the female rats exposed to 0.5 or 1.0
      ppm of ozone. Collagen in the lungs of the females also contained relatively more
      hydroxylysine-derived crosslinks than did lung collagen from age-matched control
      animals. No excess of type I procollagen mRNA could be appreciated by in situ
      hybridization in lungs of the rats exposed to 1.0 ppm of ozone for 20 months,
      although this mRNA was detected in occasional alveolar interstitial cells at 2
      months of exposure to ozone under the same protocol. These findings indicate that
      chronic exposure of rats to ozone causes mild, persistent fibrosis. The
      significance of these observations with regard to human health risks of
      chronically inhaling ozone at ambient levels in polluted air remains to be
      determined.

PMID- 8266341
TI  - The management of scorpion envenomation 1993.

PMID- 8266342
TI  - Toxins as tools in the study of sodium channel distribution in the muscle fibre
      membrane.
AB  - The number of tetrodotoxin molecules bound to the membrane of the fibres of
      muscles in normal conditions and after detubulation produced by glycerol-induced
      osmotic shock pointed to a higher sodium channel density at the surface membrane
      than at the membrane in the transverse tubules. Study of the maximum rate of rise
      of the action potential at the junctional and nonjunctional regions of the muscle
      fibre membrane suggested that the Na+ channel density is also not the same along
      the muscle fibre membrane, being higher at the junctional region. Further studies
      on the distribution of the Na+ channel along the muscle fibre membrane were
      carried out with the use of (1) the loose patch voltage-clamp technique, (2)
      labelling the Na+ channels with fluorescently labelled scorpion toxins, (3)
      autoradiography of localized Na+ channels with 125I-labelled scorpion toxins, and
      (4) toxins that induce persistent activation of the Na+ channel. The studies
      referred to in (1), (2) and (3) demonstrate that the density of the Na+ channel
      is much higher at the junctional region than elsewhere in the membrane of the
      muscle fibre. On the other hand, in experiments carried out on curarized rat
      diaphragms several sodium channel activating toxins (crotamine, Phoneutria
      nigriventer venom, its toxin PhTx2, veratrine) were found to produce a much
      greater depolarization of the membrane at the junctional region than at
      nonjunctional regions. However, it was also found that some toxins (veratridine,
      batrachotoxin) depolarized equally well the junctional and nonjunctional regions.
      Two alternative hypotheses to explain the uniform depolarization of the muscle
      fibre membrane induced by these toxins are suggested.

PMID- 8266344
TI  - Batrachotoxinin-A-ortho-azidobenzoate: a photoaffinity probe of the batrachotoxin
      binding site of voltage-sensitive sodium channels.
AB  - Batrachotoxin (BTX) is one of a group of potent lipid-soluble neurotoxins which
      binds voltage-sensitive sodium channels. Here we show that [3H]batrachotoxinin-A
      ortho-azidobenzoate ([3H]BTX-OAB), a photolabile derivative of BTX, binds
      covalently upon irradiation to the BTX sodium channel site of rat cerebral
      cortical synaptoneurosomes. Another ligand specific for the BTX sodium channel
      receptor, batrachotoxinin-A 20-alpha-benzoate (BTX-B), competitively inhibited
      the specific binding of [3H]BTX-OAB. The specific binding of [3H]BTX-OAB was
      increased by the addition of Leiurus quinquestriatus quinquestriatus scorpion
      venom (ScTx) and inhibited by veratridine, a member of the same class of sodium
      channel activators. Examination of the [3H]BTX-OAB-labeled components revealed
      that over 90% of the specifically incorporated [3H]BTX-OAB was recovered in lipid
      extracts of photolabeled synaptoneurosomes. Addition of tetrodotoxin (TTX) to the
      binding mixture increased the specific incorporation of [3H]BTX-OAB into protein
      components as much as 15-fold. Increasing the incubation temperature from 25
      degree C to 37 degrees C had a similar but less marked effect. We conclude that
      the BTX binding site lies at a lipid-protein interface and that treatments which
      induce conformational changes in the sodium channel protein (i.e. addition of
      TTX) can result in a reorientation of BTX at its binding site relative to the
      protein and lipid domains of voltage-sensitive sodium channels.

PMID- 8266343
TI  - Pharmacological studies of 'sapo' from the frog Phyllomedusa bicolor skin: a drug
      used by the Peruvian Matses Indians in shamanic hunting practices.
AB  - The dried skin secretion from Phyllomedusa bicolor, 'sapo', is used by the Matses
      Indians of the Northern Peru, in shamanic rites mainly designed to improve luck
      in hunting. When rubbed into burned, exposed areas of the skin, the drug causes
      the prompt appearance of violent peripheral gastrointestinal and cardiovascular
      effects soon followed by remarkable central effects (increase in physical
      strength, heightening of senses, resistance to hunger and thirst, exalted
      capacity to face stress situations). All the peripheral and most of the central
      effects of 'sapo' can be ascribed to the exceptionally high content of the drug
      (up to 7% of its weight) in potently active peptides, easily absorbed through the
      burned, inflamed areas of the skin. The concentration in 'sapo' of the single
      peptides (phyllocaerulein, phyllomedusin, phyllokinin, demorphins and
      deltorphins) has been determined by bioassay, and peptide contents were
      correlated with the different symptoms of the 'sapo' intoxication.

PMID- 8266345
TI  - Increased insulin circulating levels induced by canatoxin in rats.
AB  - Canatoxin, a proteic neurotoxin from Canavalia ensiformis seeds, raises
      circulating insulin levels and induces hypoglycemia in rats. The hyperinsulinemia
      produced by canatoxin (6 micrograms kg-1, 20 min; 108% of increase in female
      rats) was both time and dose dependent and lasted only about 30 min, while the
      fall in blood glucose levels (around 30%) was long lasting. The hyperinsulinemic
      response to canatoxin was greater in females (+108 +/- 18%) than males (+43 +/-
      8%), but no difference was noted in the hypoglycemia. Pretreatment of rats with
      either naloxone, naltrexone, atropine or hexamethonium abolished both the
      hyperinsulinemia and the hypoglycemia. These data suggest that these phenomena
      are influenced by opioids and depend on parasympathetic stimulation.

PMID- 8266346
TI  - Isolation and characterization of synergistic hemorrhagins from the venom of the
      snake Bothrops asper.
AB  - Three hemorrhagic factors (BaH1, BH2 and BH3) were isolated from the venom of
      Bothrops asper by gel filtration on Sephacryl S-200, DEAE-Sepharose
      chromatography, metal chelate affinity chromatography and hydrophobic interaction
      chromatography. They contain 55% of the total hemorrhagic activity of the whole
      venom when they are mixed, but lose almost half of the activity if they are
      separated, indicating a synergism between the three. The main hemorrhagin is BaH1
      (Bothrops asper hemorrhagin 1); the other two are weak hemorrhagins but
      contribute to the synergism. They are acidic proteins with a pI of 4.5, 5.2 and
      5; their mol. wt is 64,000, 26,000 and 55,000 respectively. The minimal
      hemorrhagic dose (MHD) of BaH1, BH2 and BH3 is 0.18, 2 and 1.6 micrograms, with a
      specific activity 55, 5 and 6.25 higher than that of the whole venom. The
      hemorrhagic activity of all three factors was inhibited by EDTA and ortho
      phenathroline, indicating that the hemorrhagic activity is metal dependent.
      Phosphoramidon, soybean trypsin inhibitor, PMSF, pepstatin and aprotinin did not
      affect the hemorrhagic activity of the isolated factors.

PMID- 8266347
TI  - Study of factors that influence the clinical response to ciguatera fish
      poisoning.
AB  - A 1-year observational study of all standardized medical records of ciguatera
      fish poisoning notified cases was conducted in French Polynesia. The objective
      was to determine the factors that influence the clinical response to ciguatera
      fish poisoning. During the year 1991, there were 551 cases notified on
      standardized code sheets by physicians (notification rate 276 per 100,000). The
      mean age was 36.6 years (S.D. 15.6). The largest age group was that between 30
      and 49 years old (notification rate 562 per 100,000). The gender ratio (M/F) was
      1.6. Of the 551 cases, 257 (47%) presented with a history of a previous attack. A
      clinical score was calculated to assess the outcome for each case. The adjusted
      odds ratio (OR) for a severe disease (33% with a score greater than 5) was
      significantly increased when the fish ingested was carnivorous (OR = 1.62, P =
      0.02) and when a history of a previous attack was reported (OR = 1.71, P =
      0.006). The increased severity of multiple episodes and the increase of the
      notification rate with age suggest a possible accumulation of toxin in the human
      organism.

PMID- 8266348
TI  - Apparent relationships between toxins elaborated by the cyanobacterium
      Trichodesmium erythraeum and those present in the flesh of the narrow-barred
      Spanish mackerel Scomberomorus commersoni.
AB  - The marine cyanobacterium Trichodesmium erythraeum contains toxic water-soluble
      material that produces signs in mice similar to those produced by water-soluble
      extracts of the flesh of a specimen of pelagic fish Scomberomorus commersoni from
      a batch that had been implicated in a poisoning resembling ciguatera. Extracts of
      water-soluble material from both the cyanobacterium and the fish contained toxins
      that were chromatographically indistinguishable. A peptide and an alkaloid were
      detected in partially purified extracts of the water-soluble material. In
      addition to this material toxic lipid-soluble material was present in some
      batches of T. erythraeum. Elution of this material with 9:1 chloroform:methanol
      using column chromatography produced material that was chromatographically
      indistinguishable from ciguatoxin-like material from S. commersoni and produced
      signs in mice similar to those produced by this material. Elution of the lipid
      soluble material with 97:3 chloroform:methanol yielded a toxin resembling in its
      chromatographic and toxic properties a scaritoxin-like substance from S.
      commersoni. Other toxins with Rf values lying between that of the ciguatoxin-like
      material and that of the scaritoxin-like material were also detected in extracts
      of T. erythraeum. It is postulated that T. erythraeum is the progenitor of major
      toxins carried by some ciguateric fish and that water-soluble toxins released
      into the ambient sea water by T. erythraeum may constitute a health hazard for
      humans.

PMID- 8266349
TI  - Protein phosphatase activity in cyanobacteria: consequences for microcystin
      toxicity analysis.
AB  - Hepatotoxic microcystin levels in cyanobacteria (blue-green algae) were assessed
      by an assay based on inhibition of protein phosphatases type 1 (PP1) and type 2A
      (PP2A) in crude chicken forebrain extracts using 32P-labelled glycogen
      phosphorylase as substrate. While cyanobacteria are reported to be devoid of
      phosphorylase phosphatase activity, two samples obtained from cyanobacterial
      scums, containing predominantly Anabaena circinalis, were found to contain high
      levels of a phosphorylase phosphatase activity which completely masked the
      presence of microcystin. Furthermore, samples containing predominantly
      Microcystis aeruginosa but increasing Anabaena circinalis contained sufficient
      phosphorylase phosphatase activity to cause a fourfold underestimation of
      microcystin levels. Thus, protocols for microcystin toxicity analysis should take
      into account the possible presence of endogenous phosphatase activity, thereby
      preventing underestimation of toxin levels.

PMID- 8266350
TI  - A simple and rapid method for isolating small myotoxins from rattlesnake venoms.
AB  - Many rattlesnake venoms (family Crotalidae) contain small, highly basic toxins
      which cause contracture and necrosis of skeletal muscle in experimental animals.
      Isolation of these myotoxins requires several chromatographic steps taking
      several days to complete. We report the isolation of crotamine, myotoxin a, and
      myotoxin a-like molecules from whole venom of three species of rattlesnakes using
      a Hydrazide Avidchrom Cartridge. Milligram amounts of highly purified and
      biologically active myotoxin can be obtained in 30 min to 2 hr.

PMID- 8266351
TI  - p-Bromophenacyl bromide modification of Bothrops asper myotoxin II, a lysine-49
      phospholipase A2, affects its pharmacological activities.
AB  - Modification of Bothrops asper myotoxin II, a lysine-49 phospholipase A2 variant,
      was carried out with p-bromophenacyl bromide. Modified toxin did not show changes
      in its charge and immunological properties but two of its pharmacological
      activities were modified. Myotoxic activity, measured by histology and by
      increment of creatine kinase levels in plasma of mice, was significantly reduced
      after toxin modification. In addition, liposome disruption activity was also
      significantly lower with the modified toxin both at 3 and 24 hr of incubation
      with the alkylating reagent. Some of the implications of these results on the
      structure-function relationship of myotoxins are discussed.

PMID- 8266352
TI  - Heparin or a PAF antagonist (BN-52021) prevents the acute pulmonary edema induced
      by Tityus serrulatus scorpion venom in the rat.
AB  - Experiments were performed in pentobarbital-anesthetized rats, to study the
      mechanism of the acute pulmonary edema induced by Tityus serrulatus scorpion
      venom. In control rats injection of venom (50 micrograms/100 g, i.v.) induced
      arterial hypertension and lung edema (lung/body index or LBI equal to 1.01 +/-
      0.09). In rats pretreated with heparin (100 IU/100 g 30 min previously) the venom
      induced similar hypertensive effects, but no edema was detected (LBI = 0.63 +/-
      0.06, P > 0.05). Similarly, in rats pretreated with the PAF antagonist BN-52021
      (0.5 mg/100 g, i.v., 30 min previously), the venom-induced hypertension was not
      modified but the acute pulmonary edema was prevented (LBI = 0.67 +/- 0.08, P >
      0.05). It is concluded that PAF plays an important role on the genesis of
      pulmonary edema induced by scorpion venom in the rat. It is suggested that the
      inhibitory action of heparin could be related to a decrease in the vascular
      permeability in the lungs.

PMID- 8266353
TI  - Bibliography of toxinology.

PMID- 8266354
TI  - Identifying clinically relevant carotid disease.

PMID- 8266355
TI  - Causes and mechanisms of territorial and nonterritorial cerebellar infarcts in
      115 consecutive patients.
AB  - BACKGROUND AND PURPOSE: Territorial cerebellar infarcts have mainly a
      thromboembolic mechanism. Cerebellar infarcts less than 2 cm in diameter have
      recently been reported as nonterritorial infarcts, but it is not clear whether
      they are low-flow or embolic infarcts. The aim of the present study was to
      compare the characteristics and causes of territorial and nonterritorial infarcts
      in a prospective series of 115 patients. METHODS: We collected data from 115
      consecutive patients with cerebellar infarcts (79 territorial and 36
      nonterritorial [ie, less than 2 cm]), using magnetic resonance imaging (88
      patients) and computed tomography. RESULTS: Patients with territorial infarcts
      and those with nonterritorial infarcts had similar vascular risk factors and
      clinical presentations and an equal frequency of cardiac source of embolism (32%
      versus 42%; P = NS) and of large artery occlusive disease (23% versus 19%; P =
      NS). Occlusive lesions of large arteries at angiography occurred at the level of
      one cerebellar artery (5% versus 0%; P = NS) and proximal to the ostia of the
      cerebellar arteries (18% versus 19%; P = NS). Infarcts distal to occlusive
      lesions were subdivided into unilateral vertebral artery occlusive disease
      (presumed artery-to-artery embolic mechanism; 18% versus 5%; P = NS) and low-flow
      state distal to bilateral vertebral or basilar artery occlusion (presumed
      hemodynamic mechanism; 0% versus 14%; P = .004). Patients with nonterritorial
      infarcts had more frequent hypercoagulable state (17% versus 1.25%; odds ratio,
      15.6 [95% confidence interval, 1.8 to 135]). For the remaining patients, the
      mechanism of the infarct was unknown (34% versus 22%; P = NS). CONCLUSIONS:
      Cerebellar infarcts less than 2 cm in diameter (ie, nonterritorial) have the same
      high rate of embolic mechanism as territorial infarcts (47% versus 49%; P = NS),
      have more frequent hypercoagulable state, and sometimes have a hemodynamic
      mechanism.

PMID- 8266356
TI  - Estimation of arterial stiffness, compliance, and distensibility from M-mode
      ultrasound measurements of the common carotid artery.
AB  - BACKGROUND AND PURPOSE: Arterial stiffness may indicate early vascular changes
      that predispose to the development of major vascular disease. The repeatability
      of a variety of indices of arterial stiffness calculated from a standard carotid
      arterial M-mode ultrasound image was investigated. METHODS: Twenty-six
      asymptomatic normal subjects were imaged and had blood pressure recordings on
      each of two separate occasions at least 1 day apart. Using a computer-assisted
      method, the maximum and minimum internal diameter and average wall thickness of
      the right common carotid artery were measured over several cardiac cycles, and
      the following indices of arterial stiffness and distensibility (compliance) were
      derived: the pressure-strain elastic modulus (Ep), Young's modulus (E), cross
      sectional compliance (CC), and the distensibility coefficient (DC). RESULTS: The
      repeatability of these measures, expressed as coefficients of variation, was as
      follows: Ep, 18%; E, 24%; CC, 14%; and DC, 13%. In another group of 20 subjects,
      the coefficient of variation for repeat examination by different sonographers was
      Ep, 19%; E, 20%; CC, 14%; and DC, 17% and for the one sonographer using two
      ultrasound machines was Ep, 13%; E, 13%; CC, 11%; and DC, 13%. These values
      indicate a moderate level of repeatability. In a univariate analysis each of
      these indices was significantly related to increasing age (Ep = 1.0 + 12.9 x AGE,
      r = .80; E = 314.5 + 13.9 x AGE, r = .48; CC = 22.6-0.26 x AGE, r = -.63; DC =
      64.0-0.65 x AGE, r = -.78) but not to wall thickness (all P > .47). Using
      multiple regression techniques to adjust for age, wall thickness is a significant
      predictor of distensibility (P = .017), cross-sectional compliance (P < .001),
      and the pressure-strain elastic modulus (P = .019). Because Young's modulus is
      calculated from wall thickness, it could not be included in the multivariate
      analysis. CONCLUSIONS: We conclude that estimates of carotid artery
      distensibility and cross-sectional compliance derived from M-mode ultrasound
      recordings are moderately repeatable and may provide useful additional end points
      for trials of atherosclerotic progression.

PMID- 8266357
TI  - Autonomic consequences of cerebral hemisphere infarction.
AB  - BACKGROUND AND PURPOSE: Recently, supraventricular tachycardia has been reported
      following right hemisphere stroke, suggesting a reduction in parasympathetic
      cardiac innervation after stroke of the right hemisphere. We performed power
      spectrum analysis of fluctuations in RR interval duration in the
      electrocardiogram in an attempt to determine how ischemic stroke influences
      autonomic cardiac innervation. METHODS: Power spectrum analysis of the variation
      in 256 consecutive electrocardiographic RR intervals was performed using the fast
      Fourier transformation. The area under the spectral curve from 0 to 0.5 Hz and
      the area under the portion of the curve produced by parasympathetically mediated
      respiratory variations were determined in 20 patients with right-hemisphere and
      20 patients with left-hemisphere ischemic stroke confirmed by computerized
      tomography. Data were compared with 40 age- and sex-matched healthy controls.
      RESULTS: Total cardiac autonomic innervation was reduced after a stroke of either
      hemisphere without regard to laterality. Cardiac parasympathetic innervation was
      reduced after stroke of either hemisphere with a significantly greater reduction
      after stroke on the right (P = 2.9 x 10(-5). CONCLUSIONS: Power spectral analysis
      of heart rate variability can detect autonomic consequences of stroke. The
      spectral data predict that, to the degree that cardiac arrhythmia is produced by
      unbalanced cardiac autonomic activity favoring the sympathetic system, such
      arrhythmias could be seen after stroke of either hemisphere and would be more
      common after cerebral infarction on the right. This is consistent with evidence
      from the recent literature.

PMID- 8266358
TI  - Subcortical infarction in children.
AB  - BACKGROUND AND PURPOSE: This report examines the occurrence of subcortical
      infarction in 5 children, reviews the English literature, and discusses
      evaluation of this uncommon childhood illness. METHODS: Clinical characteristics
      and neurological follow-up were examined in children who presented with
      subcortical infarction within the past 7 years. The English literature over the
      previous 20 years was reviewed to identify similar patients with radiological
      documentation of subcortical infarction. RESULTS: Mean age of the patients in
      this series was 4.8 years (range, 4 months to 12 years); 3 children were female.
      Three patients presented with the sudden onset of hemiparesis, 1 with dystonia,
      and 1 with fever and focal seizures. Protein C deficiencies were demonstrated in
      2 children; a cardiomyopathy was seen in 1 patient. Mean follow-up was 1.5 years.
      Two patients were neurologically normal, mild residual symptoms persisted in 2,
      and 1 patient showed severe dystonia. The literature analysis indicated that
      specific risk factors were described in 79 patients; complete clinical analysis
      was available for 51 patients. In the latter group, the mean age was 5.7 years;
      26 children were female. Forty-six presented with hemiplegia, 4 with dystonia,
      and 1 with focal seizures. Follow-up greater than 5 months in 29 patients showed
      complete or good resolution of deficits in 23. Specific risk factors such as
      infection, trauma, hematologic disorders, or cardiac or vascular abnormalities
      were identified in 62 of 79 children. CONCLUSIONS: This analysis indicates that
      children with subcortical infarction usually presented with acute hemiparesis.
      Risk factors were identified in the majority of children, and follow-up
      demonstrated good or complete resolution of neurological deficits in 80% of the
      patients.

PMID- 8266359
TI  - Morphometry of structural preservation of tunica media in aged and hypertensive
      human intracerebral arteries.
AB  - BACKGROUND AND PURPOSE: Medial smooth muscle cell necrosis has been reported as a
      lesion that may precede angionecrosis, which is a major cause of not only
      hypertensive brain hemorrhage but also lacunar infarct. We morphometrically
      studied a loss of smooth muscle cells in the media of cerebral arteries in
      relation to clinical risk factors. METHODS: The lateral striate, ie, perforating
      arteries and the medullary arteries in the subcortical white matter of the
      temporal lobe (100 to 400 microns in diameter) were histologically investigated
      in 121 autopsied brains. Medial area was measured quantitatively, and the number
      of nuclei of smooth muscle cells in the area was calculated in 1210 cross
      sectional arteries of histological sections. The influence on the structural (ie,
      smooth muscle cell) preservation of the tunica media (ratio of number of smooth
      muscle cell nuclei to medial area [N-MA ratio]) of age, blood pressure, serum
      lipids, and presence of absence of extracerebral severe atherosclerosis was
      investigated. RESULTS: The N-MA ratio decreased slightly with age in both
      arteries. A reverse correlation between N-MA ratio and age was seen in groups
      both with and without hypertension. The mean N-MA ratio in the hypertensive group
      was significantly lower than that of the nonhypertensive group (P < .001) in all
      decades of life. The mean N-MA ratio of the perforating arteries was slightly
      lower than that of the medullary arteries in both groups. Severe atherosclerosis
      of the internal carotid arteries, even with hypertension, mitigated a decrease of
      the N-MA ratio, which was as slight as that in the nonhypertensive group. Serum
      cholesterol in this group was higher than in both the conventional hypertensive
      group (P < .005) and the nonhypertensive group (P < .001). CONCLUSIONS: Although
      both hypertension and age were significant risk factors for medial smooth muscle
      cell necrosis, hypertension was relatively more significant. Medial smooth muscle
      cells of the perforating arteries in the basal ganglia were more vulnerable than
      those of the medullary arteries. Cerebral small arteries in subjects with severe
      atherosclerosis of the carotid and major cerebral arteries (hypertension in eight
      of nine subjects) may have been protected from extensive loss of medial smooth
      muscles presumably because of both high serum cholesterol and decreased wall
      tensile stress associated with reduced blood perfusion due to severe
      atherosclerotic stenosis.

PMID- 8266360
TI  - Stroke rehabilitation outcome. A potential use of predictive variables to
      establish levels of care.
AB  - BACKGROUND AND PURPOSE: The most powerful predictors of functional recovery and
      eventual home discharge among stroke survivors are the initial severity of the
      stroke and the patient's age. We analyzed a large population of stroke
      rehabilitation admissions by stratifying subgroups with coherent outcomes in an
      attempt to define potentially more efficient patterns of providing rehabilitation
      care. METHODS: We retrospectively analyzed 520 consecutive patients admitted to a
      rehabilitation hospital (1 calendar year) with cerebral infarction or hemorrhage.
      Side of index stroke, age, and functional disability at admission were the
      independent variables. Change in functional disability and home versus nursing
      home discharge were the dependent measures. RESULTS: Recovery was overall most
      closely related to admission severity and age, but the relations between recovery
      and independent measures were complex. Patients aged < 55 years all were
      discharged home whatever their initial severity. Patients admitted with modest
      functional disability were almost all discharged home (96%), whatever their age.
      For the remainder of the patients, admission severity and age interacted to
      create two groups with very different prospects for home discharge (P < .0001).
      Within the groups that eventually returned home, there were very different rates
      of functional improvement that were directly related to length of hospital stay.
      CONCLUSIONS: Standard clinical measures available at rehabilitation admission
      carry enough predictive power to define management strategies for stroke
      survivors. A management algorithm is proposed that might increase the efficiency
      of stroke rehabilitation programs and might allow comparisons of efficacy between
      different treatment settings.

PMID- 8266361
TI  - Cerebral blood flow in frontal lesions of aneurysms of the anterior communicating
      artery.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate local and remote
      regional cerebral blood flow in patients with prefrontal lesions resulting from
      rupture (and operation) of aneurysms of the anterior communicating artery.
      METHODS: The localization and severity of the lesions were evaluated by magnetic
      resonance imaging on T2 sequences. Blood flow measurements were performed in 21
      patients at least 3 weeks after surgery using single-photon emission computed
      tomography. Flow values were calculated in 10 regions of interest in each
      cerebral hemisphere and compared with those of 21 control subjects matched for
      age. RESULTS: A drop in regional cerebral blood flow, predominating on the right
      side, was observed in the frontal areas. Flow values were not reduced in the
      thalamus and striatum but were significantly elevated in the posterior cortical
      areas and cerebellum. This latter phenomenon was significantly correlated with
      the severity of frontal lesions on magnetic resonance imaging. CONCLUSIONS: Blood
      flow drop in frontal areas was correlated with the cerebral lesions, which
      predominated in the anterior prefrontal lobe, on the side of the surgical flap;
      most of these prefrontal lesions were likely due to the surgical procedure and
      not to classic arterial spasm. Elevated perfusion in the temporo-parieto
      occipital cortex and cerebellum might be due to the release of a physiological
      inhibition exerted by the prefrontal cortex.

PMID- 8266363
TI  - Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after
      cardiac arrest and resuscitation.
AB  - BACKGROUND AND PURPOSE: We sought to examine the effect of moderate hypothermia
      (30 degrees C to 32 degrees C) initiated after resuscitation on the scavenging
      systems of free radicals and lipid peroxidation in canine brain tissue after
      cardiac arrest and resuscitation. METHODS: Twenty-one dogs were divided into four
      groups: group A, nonischemic controls (shams) (n = 4); group B, 15-minute cardiac
      arrest without reperfusion (n = 4); group C, 15-minute cardiac arrest and
      standard resuscitation (n = 6); and group D, 15-minute cardiac arrest and
      hypothermic resuscitation (n = 7). During the period of 10 to 120 minutes after
      resuscitation, brain temperature and core temperature in group D remained at 30
      degrees C to 32 degrees C and were 4 degrees C to 5 degrees C lower than in group
      C. For each dog, a sample of right parietal cerebral cortex was obtained from
      group A, group B, or from group C and group D at 2 hours after resuscitation. The
      sample was assayed for tissue malondialdehyde (MDA), the content of reduced
      glutathione (GSH), and the activities of superoxide dismutase (SOD) and
      glutathione peroxidase (GSH-PX). RESULTS: In group B, a 15-minute cardiac arrest
      induced an increase in MDA, a significant reduction of GSH, and no change in SOD
      and GSH-PX activities compared with group A. In group C, there were further
      increases in MDA and reductions in GSH content and GSH-PX activity compared with
      group A; SOD activity remained substantially unchanged. The content of MDA was
      higher in group D than in group A but less elevated in group D than in group C.
      The GSH content and SOD and GSH-PX activities were significantly higher in group
      D than in group C. CONCLUSIONS: Moderate hypothermia initiated after
      resuscitation can significantly inhibit the accumulation of lipid peroxidation
      products and the consumption of free radical scavengers in the brain tissue.

PMID- 8266362
TI  - Responses of cerebral arterioles to activation of beta-adrenergic receptors
      during diabetes mellitus.
AB  - BACKGROUND AND PURPOSE: Diabetes mellitus impairs reactivity of large peripheral
      arteries and arterioles to activation of beta-adrenergic receptors. The goal of
      this study was to determine whether diabetes mellitus alters dilatation of
      cerebral arterioles to activation of beta-adrenergic receptors. METHODS: In vivo
      diameter of pial arterioles was measured in nondiabetic and diabetic
      (streptozotocin 50 to 60 mg/kg IP) rats during superfusion with isoproterenol,
      forskolin, and nitroglycerin. In addition, we examined the contribution of nitric
      oxide or a nitric oxide-containing compound in dilatation of pial arterioles in
      response to the agonists. RESULTS: Dilatation of pial arterioles in response to
      isoproterenol was significantly less in diabetic compared with nondiabetic rats
      (3 +/- 2% versus 14 +/- 1%, respectively, for 1.0 mumol/L isoproterenol). In
      contrast, dilatation of pial arterioles in response to nitroglycerin and
      forskolin was similar in nondiabetic and diabetic rats. Furthermore, dilatation
      of pial arterioles in nondiabetic rats in response to isoproterenol and forskolin
      was not related to the synthesis and release of nitric oxide or a nitric oxide
      containing compound. CONCLUSIONS: The findings of the present studies suggest
      that diabetes mellitus impairs dilatation of cerebral resistance arterioles in
      response to activation of beta-adrenergic receptors. Impairment of beta
      adrenergic-mediated dilatation of cerebral arterioles during diabetes mellitus
      does not appear to be related to an alteration in cyclic adenosine monophosphate,
      since forskolin produced similar vasodilatation in nondiabetic and diabetic rats.

PMID- 8266364
TI  - Recovery of sensorimotor function after distal middle cerebral artery
      photothrombotic occlusion in rats.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to delineate the
      behavioral correlates of focal thrombotic occlusion of the distal middle cerebral
      artery in rats and to compare the pattern of deficits and subsequent recovery to
      that following proximal middle cerebral artery occlusion. METHODS: Ten Sprague
      Dawley rats underwent photothrombotic occlusion of the distal middle cerebral
      artery with tandem occlusion of the common carotid arteries (dMCAO group); 10
      animals served as operated controls. Beginning on postischemia day 2, animals
      were given a battery of five tests that assessed sensorimotor integration,
      attentional mechanisms, and muscle strength; testing continued twice weekly until
      day 30. Nine days of cognitive testing on the learning set of the water maze task
      were then given. Infarct volume and hemispheric atrophy were determined for each
      dMCAO animal. RESULTS: After ischemia, the dMCAO group exhibited significant
      behavioral deficits in posture reflex, ability to place a forelimb to various
      stimuli, limb adduction during rearing, and neglect of contralateral space. These
      deficits showed variable recovery rates. No deficits were observed in muscle
      strength or cognitive performance. The deficits and patterns of recovery were
      related to infarct location and to degree of hemisphere atrophy. CONCLUSIONS: The
      present study suggests that a battery of tests is necessary to fully characterize
      the pattern of behavioral deficits after focal cerebral ischemia. Location of
      infarct damage and associated degree of hemispheric atrophy were important
      variables in determining behavioral outcome. The present results are compared
      with those of the more traditional model of electrocoagulation of the proximal
      middle cerebral artery.

PMID- 8266365
TI  - Human copper-zinc superoxide dismutase transgenic mice are highly resistant to
      reperfusion injury after focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: We have demonstrated in a previous study that superoxide
      radicals play a role in the pathogenesis of cerebral infarction, using a
      transgenic mouse model of distal middle cerebral artery occlusion, permanent
      ipsilateral cerebral carotid artery occlusion, and 1-hour contralateral cerebral
      carotid artery occlusion that produced infarction only in the cortex. However,
      the role of superoxide radicals in reperfusion injury in transgenic mice
      overexpressing superoxide dismutase (SOD) is unknown. Using a mouse model of
      intraluminal blockade of middle cerebral artery that produced both cortical and
      striatal infarction, we now further examined the role of superoxide radicals in
      ischemic cerebral infarction after reperfusion in transgenic mice overexpressing
      human CuZn-SOD activity. METHODS: Transgenic mice of strain Tg HS/SF-218,
      carrying human SOD-1 genes, and nontransgenic littermates were anesthetized with
      chloral hydrate (350 mg/kg IP) and xylazine (4 mg/kg IP). Physiological
      parameters were maintained at a normal range using a 30% O2/70% N2O gas mixture
      inserted via an inhalation mask. Body temperature was maintained at 37 +/- 0.5
      degrees C by using a heating pad throughout the studies. The middle cerebral
      artery occlusion was achieved with a 5-0 rounded nylon suture placed within the
      internal cerebral artery for 3 hours followed by the removal of the suture to
      allow reperfusion for another 3 hours. Cerebral infarct size in brain slices and
      infarct volume, neurological deficit, cortical blood flow, and glutathione levels
      were measured in both transgenic and nontransgenic mice. RESULTS: Compared with
      the nontransgenic mice, the infarcted areas were significantly decreased in
      coronal slices from transgenic mice. The infarct volume (in cubic millimeters)
      was reduced by 26% in transgenic mice after ischemia and reperfusion. This
      decrease in the infarct volume in transgenic mice closely paralleled the reduced
      neurological deficits. Introduction of the suture to block blood supply to the
      middle cerebral artery territory produced a rapid decrease in the relative
      surface blood flow in the ipsilateral core and the peri-ischemic (penumbra)
      areas. There were no significant differences in the local cerebral blood flow in
      the ischemic core or the penumbra areas between the transgenic and nontransgenic
      groups. However, the level of reduced glutathione in the penumbra area was
      significantly higher in transgenic mice than in nontransgenic mice, whereas there
      was no difference in the reduced glutathione levels in the ischemic core between
      these two groups. CONCLUSIONS: Our study demonstrated that superoxide radicals
      play a major role in the pathogenesis of cerebral infarction in reperfusion
      injury after a focal stroke. The reduction in infarct volume and neurological
      deficits is not dependent on the changes in cerebral blood flow but rather
      correlate with reduced oxidative stress in the ischemic brain tissue, which was
      indicated by the relatively high levels of endogenous reduced glutathione in
      transgenic mice.

PMID- 8266366
TI  - Estimation of cerebral blood flow through color duplex sonography of the carotid
      and vertebral arteries in healthy adults.
AB  - BACKGROUND AND PURPOSE: To noninvasively estimate cerebral blood flow volume, a
      prospective study of color duplex sonography of the common, external, and
      internal carotid arteries and vertebral arteries of healthy adults was done.
      Cerebral blood flow was calculated with the sum of flow volumes in the internal
      carotid and vertebral arteries of both sides. METHODS: Using a 7.0-MHz linear
      transducer of a computed sonography system, cervical arteries of 48 volunteers
      (23 women, 25 men; mean age, 35 +/- 12 years) were examined. We measured angle
      corrected time-averaged velocities and the diameter of the vessels and calculated
      the flow volumes of all arteries. In addition, peak systolic, maximum end
      diastolic, and time-averaged maximum velocities and the resistance, pulsatility,
      and spectral broadening indexes were determined. Furthermore, we analyzed the
      side-to-side difference, age dependence, and long-term reproducibility of these
      parameters. RESULTS: The mean +/- SD values of flow volumes in the common,
      internal, and external carotid and vertebral arteries were 470 +/- 120, 265 +/-
      62, 160 +/- 66, and 85 +/- 33 mL/min on either side, respectively. Total cerebral
      blood flow was 701 +/- 104 mL/min (corresponding to 54 +/- 8 mL/100 g per
      minute), with no variation in age or sex. Long-term reproducibility of cerebral
      blood flow and flow volumes in all vessels was significant (P < .01).
      CONCLUSIONS: We conclude that color duplex sonography of cervical arteries is
      potentially a practical method for estimating total cerebral blood flow. This
      noninvasive technique may be ideally suited for bedside and follow-up
      examinations of the critically ill patient. In future studies it should be
      compared with established radionuclide techniques.

PMID- 8266367
TI  - Influence of pH on calcium influx during hypoxia in rat cortical brain slices.
AB  - BACKGROUND AND PURPOSE: Acidity of brain intracellular and extracellular fluids
      appears to increase brain injury from stroke, but low extracellular pH decreases
      the activity of N-methyl-D-aspartate receptor ion channels and decreases calcium
      influx into isolated neurons. To further investigate the role of acid-base
      balance in hypoxic brain injury, we studied the influences of intracellular and
      extracellular pH on calcium influx in cortical brain slices during hypoxia.
      METHODS: Intracellular calcium ([Ca2+]i) and pH (pHi) were measured
      fluorometrically with the dyes fura-2 and biscarboxyethyl carboxyfluorescein,
      respectively, during two types of hypoxia: (1) slice perfusate equilibrated with
      N2/CO2 at pH 6.6 or 6.2 ("gaseous hypoxia") or (2) perfusate equilibrated with
      95% O2/5% CO2 plus 100 mumol/L NaCN at pH 7.3, 6.6, or 6.2 ("chemical hypoxia").
      RESULTS: Changes in perfusate pH under aerobic conditions did not change [Ca2+]i.
      However, influx of calcium caused by gaseous or chemical hypoxia increased
      significantly with decreasing perfusate pH. During chemical hypoxia, the
      elevation in [Ca2+]i at perfusate pH 6.2 was twice that at perfusate pH 7.3.
      Change in [Ca2+]i was correlated with perfusate pH but not pHi. CONCLUSIONS:
      These results, which differ from previous studies showing acid inhibition of
      calcium influx in isolated neurons, suggest that low extracellular pH may
      exacerbate cellular injury during severe hypoxia or ischemia in the intact brain.

PMID- 8266368
TI  - Impaired relaxation of the carotid artery during activation of ATP-sensitive
      potassium channels in atherosclerotic monkeys.
AB  - BACKGROUND AND PURPOSE: This study examined the hypotheses that (1)
      atherosclerosis impairs relaxation of the carotid artery in response to
      activation of adenosine triphosphate (ATP)-sensitive potassium channels and (2)
      regression of atherosclerosis restores the response toward normal. METHODS:
      Isometric tension was measured in rings of carotid artery taken from normal,
      atherosclerotic, and regression monkeys and precontracted submaximally with
      prostaglandin F2 alpha. RESULTS: Relaxation in response to acetylcholine was less
      in atherosclerotic compared with normal arteries (5 +/- 6% versus 54 +/- 4% [mean
      +/- SE] in response to 3 x 10(-8) mol/L acetylcholine, P < .01). Relaxation in
      response to aprikalim, a direct activator of ATP-sensitive potassium channels,
      was also less in atherosclerotic than in normal arteries (32 +/- 7% versus 69 +/-
      5% during 10(-6) mol/L aprikalim, P < .01). Relaxation in response to aprikalim
      but not to acetylcholine or nitroprusside was inhibited almost completely by
      glibenclamide (4 mumol/L), a selective inhibitor of ATP-sensitive potassium
      channels. Relaxation in response to low but not high (10(-6) to 10(-5) mol/L)
      concentrations of sodium nitroprusside was less in atherosclerotic than in normal
      arteries. Regression of atherosclerosis tended to restore responses to
      acetylcholine, but not responses to nitroprusside or aprikalim, toward normal.
      CONCLUSIONS: These findings suggest that atherosclerosis impairs relaxation of
      the carotid artery in response to activation of ATP-sensitive channels. Impaired
      responses may be due, in part, to nonspecific impairment of relaxation.
      Regression of atherosclerosis did not restore responses of the carotid artery
      toward normal.

PMID- 8266369
TI  - Angiotensin II administration improves cerebral blood flow in cardiopulmonary
      arrest in swine.
AB  - BACKGROUND AND PURPOSE: Cerebral blood flow during cardiopulmonary resuscitation
      is inadequate to meet cerebral metabolic demand. Adrenergic agonists improve
      cerebral blood flow, but clinical trials of increased doses in adults have not
      shown improved outcome from cardiac arrest. This may be due to adverse beta
      agonist-mediated effects. The purpose of this study was to determine the effect
      of angiotensin II, a potent nonadrenergic vasopressor, on cerebral blood flow in
      cardiac arrest. METHODS: Eleven immature swine were anesthetized and instrumented
      for regional blood flow measurements with radiolabeled microspheres. A sagittal
      sinus catheter was placed for blood gas determination. A blood flow measurement
      was performed in normal sinus rhythm and ventricular fibrillation induced. After
      10 minutes of ventricular fibrillation, cardiopulmonary resuscitation was begun
      and a blood flow measurement performed. Angiotensin II at a dose of 50
      micrograms/kg was administered intravenously at 13 minutes of ventricular
      fibrillation. A blood flow measurement was performed and defibrillation
      attempted. A fourth blood flow measurement was obtained if return of spontaneous
      circulation occurred. RESULTS: Total cerebral blood flow was 46.4 mL/min per 100
      g in normal sinus rhythm. This fell to 6.9 mL/min per 100 g with cardiopulmonary
      resuscitation alone and rose to 30.8 mL/min per 100 g after the administration of
      angiotensin II. The improvement following angiotensin II was statistically
      different (P = .002). Cerebral blood flow further rose in the animals that had
      return of spontaneous circulation to 73.9 mL/min per 100 g. CONCLUSIONS:
      Angiotensin II in a dose of 50 micrograms/kg significantly improves cerebral
      blood flow in this model of cardiac arrest.

PMID- 8266370
TI  - Venous sinus thrombosis associated with androgens in a healthy young man.
AB  - BACKGROUND: Cerebral venous sinus thrombosis is rare and can be promoted by
      various conditions. We report the case of cerebral venous thrombosis in a patient
      using androgens. CASE DESCRIPTION: A 31-year-old man using androgens for
      bodybuilding was admitted for headache and vomiting. He had cerebral venous sinus
      thrombosis, but extensive examinations did not reveal any known cause.
      CONCLUSIONS: We suggest that androgens may promote cerebral venous thrombosis.
      The mechanisms of venous thrombosis related to androgens may be platelet
      activation or an increase in coagulation factors. Because androgen use may be
      frequent and hidden in athletes, it may be an underestimated cause of cerebral
      venous sinus thrombosis in the young.

PMID- 8266371
TI  - Basilar artery occlusion in a young patient with Wegener's granulomatosis.
AB  - BACKGROUND AND PURPOSE: Stroke is an uncommon sequela of Wegener's
      granulomatosis, resulting primarily from vasculitic infiltration of small to
      medium-sized vessels. We describe a young patient with Wegener's granulomatosis
      and basilar artery occlusion. CASE DESCRIPTION: A 26-year-old man with
      histopathologically confirmed Wegener's granulomatosis suffered a brain stem
      stroke 24 hours after open lung biopsy. Angiography revealed midbasilar artery
      occlusion. CONCLUSIONS: Patients with Wegener's granulomatosis may experience
      premature large cerebral vessel occlusion. Putative etiologies in our patient
      include vasculitis, postoperative hypercoagulability, and/or intraoperative neck
      positioning leading to embolization.

PMID- 8266372
TI  - Involuntary tonic spasms of a limb due to a brain stem lacunar infarction.
AB  - BACKGROUND AND PURPOSE: Although repetitive involuntary movements are a well
      recognized manifestation of carotid occlusive disease, similar movements have not
      been reported with a lacunar infarction outside of the basal ganglia or
      subthalamic nucleus. We describe a man with tonic spasms associated with a
      lacunar infarction in the right ventral pons. CASE DESCRIPTION: Involuntary tonic
      spasms of a paretic limb developed acutely in a 69-year-old hypertensive man with
      a clinical presentation of pure motor hemiparesis. Magnetic resonance imaging
      demonstrated a lacunar infarction of the ventral pons. There was no evidence for
      carotid occlusive disease. An electroencephalogram recorded during the movements
      showed no abnormality. The abnormal movements responded well to treatment with
      oral diazepam. CONCLUSIONS: A brain stem lacunar infarction may be associated
      with involuntary tonic limb spasms clinically similar to those reported as
      paroxysmal symptoms of multiple sclerosis.

PMID- 8266373
TI  - Stroke prevention. An opportunity for efficient utilization of health care
      resources during the coming decade.
AB  - BACKGROUND: Stroke is unique among neurological diseases, since it has a high
      prevalence and burden of illness, high economic cost, and is preventable.
      Epidemiological approaches to stroke prevention include the "high-risk" and
      "mass" approaches. In this review we discuss these preventive strategies, target
      host and discretionary risk factors that are amenable to these measures, and
      discuss potential cost savings. SUMMARY OF REVIEW: Projected numbers of strokes
      prevented for specific stroke risk factors were estimated by using the population
      attributable risk estimation for hypertension, cigarette smoking, atrial
      fibrillation, and heavy alcohol consumption. The projected numbers of strokes
      that could be prevented were substantial and highest for hypertension and
      cigarette smoking. Projected yearly cost of stroke associated with these two
      treatable factors was also substantial. CONCLUSIONS: The prevention of stroke can
      be accomplished by the high-risk or mass approach or a combination of these
      approaches. The high-risk approach prevents strokes but is also expensive. The
      mass approach may be more cost-effective, which could lead to substantial
      savings, but this needs to be investigated.

PMID- 8266374
TI  - Risk factors for cervical atherosclerosis in patients with transient ischemic
      attack or minor ischemic stroke.

PMID- 8266375
TI  - Denial of illness and depression in stroke.

PMID- 8266376
TI  - Leukocytes in acute stroke.

PMID- 8266377
TI  - Transesophageal echocardiographic findings in stroke subtypes.
AB  - BACKGROUND AND PURPOSE: Transesophageal echocardiography has a high yield for
      detecting potential cardiac sources of embolism in patients with clinical risk
      factors for cardioembolism or unexplained stroke. The yield in other stroke
      subtypes is unknown. METHODS: We classified 145 consecutively admitted patients
      into stroke subtypes based on clinical findings, brain imaging, and carotid
      ultrasound. Both transesophageal and transthoracic echocardiography were
      performed to detect left atrial thrombi, spontaneous echo contrast, atrial septal
      aneurysm, interatrial shunts, ventricular thrombus or aneurysm, and myxomatous
      mitral valve. RESULTS: Transesophageal echocardiography documented at least one
      of these findings in 46% of the patients compared with an 8% yield on the
      transthoracic study (P = .002). The yield of transesophageal echocardiography was
      substantial in all stroke subgroups. Patients with clinical risk factors for
      cardiac embolism had the highest frequency of spontaneous echo contrast (P =
      .001). Atrial septal aneurysms were most frequent in patients with lacunar
      syndromes (P = .012), and interatrial shunts were common in all stroke subtypes.
      CONCLUSIONS: Transesophageal echocardiographic findings vary considerably between
      stroke subgroups.

PMID- 8266378
TI  - Magnetic resonance imaging of thrombosed dural sinuses.
AB  - BACKGROUND AND PURPOSE: Magnetic resonance imaging should have the potential to
      replace angiography in the diagnosis of dural sinus thrombosis. Concerning time
      dependent signal changes of the thrombus, we intended to develop a standardized
      examination protocol for routine use in suspected dural sinus thrombosis.
      METHODS: The time-dependent signal changes of thrombosed dural sinuses were
      studied in 23 consecutive patients by multiplanar spin-echo and flow-sensitive
      sequences. Signal intensities and thrombus homogeneity were graded and related to
      the time after clinical onset and the results of the magnetic resonance
      angiography. RESULTS: Four stages of the thrombus evolution could be observed.
      The acute thrombosis (days 1 to 5) appeared strongly hypointense in T2-weighted
      images and isointense in spin density- and T1-weighted images. In the subacute
      stage (up to day 15) the thrombus signal was strongly hyperintense in T1- and T2
      weighted images. The third stage began in the third week after clinical onset.
      The thrombus signal was decreased in all sequences and showed an increasing
      inhomogeneity. The fourth (late) stage was characterized by either the
      restitution of blood flow or the persistence of a residual thrombus. CONCLUSIONS:
      Each stage requires a different diagnostic approach. With the combined use of
      spin-echo and gradient-echo sequences, it is possible to make the diagnosis of
      acute thrombosis; in the second stage, multiplanar spin-echo sequences are
      sufficient. Diagnosis of dural sinus thrombosis can be established accurately
      with magnetic resonance imaging in the first two stages. However, the diagnosis
      of the later stages is difficult because of inhomogeneous signs of recanalization
      and flow phenomena. Therefore, a suspected older dural sinus thrombus still
      requires intra-arterial angiography as the primary diagnostic tool.

PMID- 8266379
TI  - Initial experience with intravascular ultrasound imaging during carotid
      endarterectomy.
AB  - BACKGROUND AND PURPOSE: To assess the feasibility of intravascular ultrasound
      imaging during carotid endarterectomy. METHODS: Intravascular ultrasound imaging
      was performed during carotid endarterectomy in eight patients using an over-the
      wire catheter system with a 30-MHz ultrasound probe. In vitro studies were
      carried out before the intraoperative application, paying special attention to
      visualization of the wall layers of normal carotid arteries, structures of more
      or less diseased vessels, and surgically placed materials such as patch, suture
      material, and fibrin glue. Although intravascular ultrasound failed to
      distinguish between intima and media in areas of normal intima, fibrotic and
      calcified plaques were detected clearly. Dacron patch as well as sutures were
      identified as highly reflective structures. RESULTS: In seven of the eight
      patients studied, intravascular ultrasound yielded cross-sectional images of good
      quality allowing identification of the vessel layers and the structures at the
      endarterectomy site. In all patients the three layers of the vessel wall were
      clearly differentiated and the transition zone between the site of endarterectomy
      and the genuine vessel appeared smooth without intimal flaps or residual
      arteriosclerotic plaques. In one patient severe eccentric thickening of the media
      was detected in the distal internal carotid artery. Neither damage of the vessel
      layers by the shunt nor thrombus formation in the operating area and the internal
      carotid artery were detected. CONCLUSIONS: Intravascular ultrasound lends itself
      as a potentially valuable method of quality control during carotid
      endarterectomy. The method seems to enable an accurate evaluation of the
      endarterectomy site and the search for residual plaques.

PMID- 8266380
TI  - Blinded-reader comparison of magnetic resonance angiography and duplex
      ultrasonography for carotid artery bifurcation stenosis.
AB  - BACKGROUND AND PURPOSE: We compared two-dimensional time-of-flight magnetic
      resonance angiography (MRA) and duplex ultrasonography with arteriography for the
      detection of 70% to 99% stenoses at the carotid artery bifurcation (ie, surgical
      disease according to findings of the North American Carotid Endarterectomy
      Trial). METHODS: Three blinded readers independently measured stenoses on MRA in
      73 vessels from 38 patients. Duplex ultrasonography was available in 66 vessels
      from 35 of these patients, and blinded reading was performed by one reader.
      Comparison was made to arteriography. RESULTS: Magnetic resonance angiography
      demonstrated a sensitivity of 92.4%, specificity of 74.5%, and negative
      predictive value of 95.8% for 70% to 99% stenoses. Interobserver agreement was
      high (kappa = 0.91). Absence of signal at stenoses with evidence of distal flow
      usually, but not always, corresponded to surgical disease. Duplex ultrasonography
      demonstrated a sensitivity of 81.0%, specificity of 82.2%, and negative
      predictive value of 90.2% for surgical disease. There was no significant
      difference between MRA and duplex ultrasonography for the sensitivity or
      specificity in detecting 70% to 99% stenoses (P > .1, exact form of the McNemar
      test). MRA had no false positives or false negatives for complete occlusions of
      the carotid artery, whereas duplex ultrasonography missed one occlusion and
      falsely called two patent vessels occluded. In seven cases, both MRA and duplex
      ultrasonography overestimated stenoses to miscategorize them as surgical disease.
      CONCLUSIONS: Although the sensitivity and specificity of MRA and duplex
      ultrasonography are not significantly different for distinguishing surgical and
      nonsurgical degrees of stenosis at the carotid bifurcation, MRA has some
      advantages that may make it the screening test of choice. Concordant MRA and
      duplex ultrasonography for surgical disease does not necessarily obviate the need
      for catheter arteriography.

PMID- 8266381
TI  - Stroke risk profile: adjustment for antihypertensive medication. The Framingham
      Study.
AB  - BACKGROUND AND PURPOSE: We sought to modify existing sex-specific health risk
      appraisal functions (profile functions) for the prediction of first stroke that
      better assess the effects of the use of antihypertensive medication. METHODS:
      Health risk appraisal functions were previously developed from the Framingham
      Study cohort. These functions were Cox proportional hazards regression models
      relating age, systolic blood pressure, diabetes mellitus, cigarette smoking,
      prior cardiovascular disease, atrial fibrillation, left ventricular hypertrophy
      by electrocardiogram, and the use of antihypertensive medication to the
      occurrence of stroke. Closer examination of the data indicated that
      antihypertensive therapy effect is present only for systolic blood pressures
      between 110 and 200 mm Hg. Adjustments to the regressions to better fit the
      observed data were developed and tested for statistical significance and goodness
      of-fit of the model residuals. RESULTS: Modified functions more consistent with
      the data were developed, and, from these, tables to evaluate 10-year risk of
      first stroke were computed. CONCLUSIONS: The stroke profile can be used for
      evaluation of the risk of stroke and suggestion of risk factor modification to
      reduce risk. The effect of antihypertensive therapy in the evaluation of stroke
      risk can now be better evaluated.

PMID- 8266382
TI  - Blood pressure treatment slows the progression of carotid stenosis in patients
      with isolated systolic hypertension.
AB  - BACKGROUND AND PURPOSE: The Systolic Hypertension in the Elderly Program (SHEP)
      was a randomized trial testing the efficacy of treating systolic hypertension in
      older adults. A significant reduction in stroke risk was observed among
      participants assigned to active treatment. Serial carotid duplex scans were
      performed on 129 participants at the University of Pittsburgh center, and rates
      of progression and regression of carotid stenosis were observed. METHODS: Changes
      in blood flow velocity ratios were used to detect progression because they can be
      reliably measured and their relation to degree of residual lumen is known.
      Progression required the development of a 40% to 50% diameter stenosis when
      stenosis was not initially present or, if already present, further reduction in
      the lumen diameter. Regression required the absence of a 40% to 50% diameter
      stenosis when stenosis was initially present or a stenosis significantly less
      severe than that initially seen. RESULTS: Progression occurred in 22% (28/129) of
      participants and regression in 16% (8/49). Progression of carotid stenosis
      occurred more often among participants randomized to placebo as compared with
      active treatment (31% versus 14%, P = .020). All eight patients exhibiting
      regression were randomized to active treatment. In multivariate analysis,
      participants assigned to placebo had 4.3 times greater odds of progressing than
      participants assigned to active treatment. Other factors significantly related to
      progression were higher degree of plaque at baseline, low high-density
      lipoprotein-3, high lipoprotein(a), and younger age. CONCLUSIONS: Treating
      systolic hypertension appears to slow progression of carotid stenosis. Similar
      effects occurring in the intracranial vessels may be one reason for the
      substantial decrease in stroke among SHEP participants assigned to active
      treatment.

PMID- 8266383
TI  - The role of lifestyle factors in the etiology of stroke. A population-based case
      control study in Perth, Western Australia.
AB  - BACKGROUND AND PURPOSE: We sought to examine risk factors for all strokes and for
      ischemic stroke and primary intracerebral hemorrhage separately. METHODS: This
      was a population-based case-control study. Each case subject meeting World Health
      Organization criteria for stroke (n = 536) from a population-based register of
      acute cerebrovascular events compiled in Perth, Western Australia, in 1989 to
      1990 was matched for age and sex with up to five control subjects drawn from the
      same geographical area. Objective confirmation of the type of stroke was
      available from computed tomography, magnetic resonance imaging, or necropsy for
      86% of the case subjects. Data on medical history and lifestyle factors were
      collected from case and control subjects by interview of the subject or a proxy
      informant. RESULTS: Current smoking, consumption of meat more than four times
      weekly, and a history of hypertension or intermittent claudication were each
      associated with increased risk in multivariate models for all strokes and for all
      first-ever strokes. Consumption of 1 to 20 g/d alcohol in the preceding week was
      associated with a significant reduction in the risk of all strokes, all ischemic
      strokes, and of primary intracerebral hemorrhage, while eating fish more than two
      times per month appeared to protect against first-ever stroke and against primary
      intracerebral hemorrhage. Diabetes mellitus was associated with a significantly
      increased risk of ischemic stroke but a decreased risk of hemorrhagic stroke.
      CONCLUSIONS: Risk factors for ischemic and hemorrhagic stroke are not exactly the
      same. Changes in lifestyle relating to tobacco and diet might make important
      contributions to further reductions in the incidence of stroke.

PMID- 8266384
TI  - A comparison of lesions in small intracerebral arteries among Japanese men in
      Hawaii and Japan.
AB  - BACKGROUND AND PURPOSE: This report examines the hypothesis that the higher risk
      of stroke among Japanese men in Japan compared with those in Hawaii is related to
      pathology in small intracerebral arteries by comparing the prevalence of such
      lesions in autopsied participants from two cohorts of Japanese men in Japan and
      Hawaii. METHODS: Existing histological sections from the left basal ganglia from
      232 men from Japan and 175 men of Japanese ancestry in Hawaii were examined for
      selected abnormalities in arteries between 100 and 300 microns in diameter by
      three pathologists. The presence of lacunar infarcts was also noted, and
      information about cerebral infarcts, cerebral hemorrhages, and atherosclerosis in
      the circle of Willis was available for the Hawaii group. RESULTS: Lacunar
      infarcts and all small intracerebral artery lesions except medial fibrosis were
      more common at every age in Japan than in Hawaii. By cause of death, all lesions
      were three or more times more prevalent among men who died of stroke than of
      noncardiovascular causes in both areas. In the Hawaii group, the small
      intracerebral artery lesions were significantly associated with autopsy evidence
      of cerebral and lacunar infarcts, and with atherosclerosis in the large arteries
      of the circle of Willis. Among a large number of risk factors measured at the
      baseline examination in Hawaii, only high blood pressure and reported usual Asian
      diet were significantly associated with one or more measures of small
      intracerebral artery lesions. CONCLUSIONS: An overview of the accumulated data
      indicated that small intracerebral artery pathology plays an important role in
      the high risk of stroke in Japanese men in Japan compared with those in Hawaii.
      These studies support the idea that hypertension is a necessary factor in the
      causal pathway, but also indicate that some other factors are involved. Some
      aspect of an Asian diet continues to be of importance for future research.

PMID- 8266385
TI  - Relation of carotid artery wall thickness to diabetes mellitus, fasting glucose
      and insulin, body size, and physical activity. Atherosclerosis Risk in
      Communities (ARIC) Study Investigators.
AB  - BACKGROUND AND PURPOSE: We tested the hypothesis that body mass, waist-to-hip
      circumference ratio, physical inactivity, diabetes, hyperglycemia, and fasting
      insulin are each positively associated with asymptomatic carotid artery wall
      thickness. METHODS: Average intimal-medial carotid wall thickness (an indicator
      of atherosclerosis) was measured noninvasively by B-mode ultrasonography in cross
      sectional samples of 45- to 64-year-old adults, both blacks and whites, free of
      symptomatic cardiovascular disease, in four US communities. RESULTS: Sample mean
      carotid wall thickness was approximately 0.7 mm in women (n = 7956) and 0.8 mm in
      men (n = 6474). Body mass, waist-to-hip ratio, work physical activity, diabetes,
      and fasting insulin were associated (P < .05) with carotid wall thickness in the
      hypothesized direction. Adjusted for age, race, smoking, body mass index, artery
      depth, and Atherosclerosis Risk in Communities field center, mean wall thickness
      was greater by 0.02 mm in women and 0.03 mm in men for a 0.07-unit (one SD)
      larger waist-to-hip ratio. Adjusted mean wall thickness was about 0.07 mm thicker
      in participants with diabetes mellitus and 0.02 mm thicker in participants with
      hyperglycemia (fasting glucose 6.4 to 7.7 mmol/L) than in subjects with fasting
      glucose < 6.4 mmol/L. Adjusted mean wall thickness increased by about 0.02 mm
      with an increase of 100 mmol/L in fasting serum insulin. CONCLUSIONS: Abdominal
      adiposity, physical inactivity, and abnormal glucose metabolism are associated
      positively with carotid intimal-medial wall thickness, suggesting these factors
      contribute to atherogenesis.

PMID- 8266386
TI  - Lipoprotein(a) and ischemic cerebrovascular disease in young adults.
AB  - BACKGROUND AND PURPOSE: Serum lipoprotein(a) level is genetically determined and
      remains almost constant throughout life. Based on this property, we investigated
      the serum lipoprotein(a) levels of ischemic stroke patients in the chronic stage
      (mean period after stroke, 27 months) and its relation to the types of ischemic
      stroke. METHODS: We measured serum lipoprotein(a) levels in 101 patients with
      chronic ischemic stroke and 37 normal control subjects, taking the clinical
      profiles into consideration. RESULTS: Lipoprotein(a) levels in patients with
      atherothrombotic stroke were 28.0 +/- 19.6 mg/dL (mean +/- SD), which were
      significantly (P < .01) higher than those in patients with lacunar stroke and in
      normal control subjects (16.4 +/- 13.5 and 11.7 +/- 10.5 mg/dL, respectively).
      The lipoprotein(a) levels in patients with atherothrombotic stroke were
      significantly higher in the subgroup who were a younger age at onset: onset
      before age 50 years, 35.3 +/- 20.5; onset at age 50 to 59, 35.4 +/- 21.7; onset
      at age 60 to 69, 17.0 +/- 12.8; and onset at age 70 or older, 16.3 +/- 6.8 mg/dL
      (P < .01 for onset before age 50 versus 60 to 69 years or 70 years or older; P <
      .01 for onset at 50 to 59 years versus 60 to 69 years or 70 years or older).
      Serum lipoprotein(a) was significantly increased (40.2 +/- 20.1 mg/dL) in young
      adults with atherothrombotic stroke (onset at younger than age 45 years) compared
      with that in patients older than 45 years (P < .01). CONCLUSIONS: We conclude
      that lipoprotein(a) is a genetic, independent, and critical risk factor for
      ischemic stroke, especially in young adults.

PMID- 8266387
TI  - Reperfusion after thrombolytic therapy in ischemic stroke measured by single
      photon emission computed tomography.
AB  - BACKGROUND AND PURPOSE: We used 99mTc-hexamethylpropyleneamine oxime single
      photon emission computed tomography (SPECT) to study cerebral perfusion in
      patients treated with streptokinase for acute ischemic stroke in an open and
      prospective study. Our primary aims were (1) to compare the extent of reperfusion
      between patients who had received thrombolytic therapy and a control group
      studied during the same period who were ineligible to receive such therapy and
      (2) to determine if, among all patients, reperfusion led to improved outcome.
      METHODS: Fifty-seven patients (22 treated with streptokinase) had two SPECT
      studies performed, the first before streptokinase administration and the second
      24 hours later. RESULTS: On the first SPECT study hyperfusion was present in the
      middle cerebral artery or anterior cerebral artery territories in 40 patients (17
      treated with streptokinase). Patients in the treatment and control groups with
      initial hypoperfusion on SPECT were well matched for the volume of the perfusion
      defect and the severity of neurological deficit. A greater number of patients who
      received streptokinase developed at least partial reperfusion (streptokinase,
      65%; control, 52%) on the second study but not significantly so (P = .43).
      Similarly, the proportion of each hypoperfused region that reperfused (P = .74)
      and the reduction in the size of the perfusion defect (P = .06) were higher in
      the streptokinase group but did not reach statistical significance. When all
      patients were considered, those who did not reperfuse had higher mortality rates
      (P = .008), less neurological improvement (P = .016), and more functional
      disability (P < .001) than patients who had reperfusion or normal perfusion
      initially. CONCLUSIONS: These findings suggest that at least some reperfusion
      during the first 48 hours of ischemic stroke is a common natural occurrence and
      is of prognostic significance. The observed trend toward better reperfusion
      indexes among patients treated with streptokinase is encouraging, but larger
      controlled trials are required to answer this definitively.

PMID- 8266388
TI  - What causes false clinical prediction of small deep infarcts?
AB  - BACKGROUND AND PURPOSE: Our goal was to identify factors that play a role in
      false clinical diagnosis of small deep infarcts. METHODS: In 350 prospectively
      registered patients with a first supratentorial ischemic stroke, we clinically
      differentiated between lacunar and nonlacunar syndromes. Using computed
      tomography (CT), we distinguished small deep and territorial infarcts and also
      recorded leukoaraiosis and asymptomatic infarcts. Degree of initial handicap,
      potential source of cardioembolic stroke, and hypertension were also noted.
      RESULTS: One hundred forty-seven patients had a lacunar and 203 a nonlacunar
      syndrome. Forty-two (12%) had a lesion visualized by CT that was compatible with
      a recent infarct but was considered inappropriate for the clinical syndrome:
      nineteen had a nonlacunar syndrome but a small deep infarct, and 23 had a lacunar
      syndrome but a territorial infarct. Patients with a nonlacunar syndrome but a
      small deep infarct were more severely disabled (a modified Rankin scale rating of
      5) (odds ratio [OR], 4.31; 95% confidence interval [CI], 1.25 to 14.88) and had a
      cardioembolic source (OR, 4.07; 95% CI, 1.04 to 15.95), leukoaraiosis (OR, 3.79;
      95% CI, 1.32 to 10.05), or asymptomatic infarcts visualized by CT (OR, 4.13; 95%
      CI, 1.45 to 11.71) compared with 124 patients with a correctly diagnosed small
      deep infarct. Twelve of 19 patients with a nonlacunar syndrome but a small deep
      infarct had a lesion in the left hemisphere, and 9 of these 12 had "aphasia."
      Patients with a lacunar syndrome but a territorial infarct more often had a
      cardioembolic source (OR, 4.02; 95% CI, 1.15 to 14.03) and a pure motor syndrome
      (OR, 4.52; 95% CI, 1.55 to 13.18) than those with lacunar syndrome but a small
      deep infarct, although 21 (91%) were in the right hemisphere. Of the first 103
      patients with lacunar stroke diagnosed by two of the study neurologists, 5 had an
      inappropriate lesion compared with 14 of the later 40 diagnosed by colleagues
      without a specific interest in cerebrovascular diseases (OR, 0.09; 95% CI, 0.03
      to 0.26). CONCLUSIONS: (1) Diagnosis of lacunar syndromes should not be
      influenced by deficit severity or the presence of a potential cardiac source of
      embolism. (2) Speech disorders should carefully be classified. (3) Routine tests
      of nondominant higher functions may be inadequate. (4) Doctors interested in
      cerebrovascular neurology have a lower failure rate in differentiating small deep
      infarcts from territorial infarcts than those less well-trained or interested in
      neurology. (5) Among the lacunar syndromes, pure motor syndrome may be the least
      specific predictor of a small deep infarct.

PMID- 8266389
TI  - Pure motor hemiparesis and sensorimotor stroke. Accuracy of very early clinical
      diagnosis of lacunar strokes.
AB  - BACKGROUND AND PURPOSE: Clinical differentiation of lacunar from nonlacunar
      strokes in the very early phase could help to exclude patients with lacunar
      stroke from pharmacologic trials designed for nonlacunar strokes, namely, those
      with thrombolytic agents. In a continuous series of acute ischemic stroke
      patients, we evaluated how accurately a clinical diagnosis of pure motor
      hemiparesis or sensorimotor stroke formulated in the first hours from onset
      predicts a lacunar stroke documented by cerebral computed tomography or by
      autopsy. METHODS: We examined 517 patients (299 men, 218 women; mean +/- SD age,
      67 +/- 10 years) within 12 hours (mean +/- SD, 6.1 +/- 3.2 hours) of the event.
      At hospital admission, we observed 151 (29%) patients with pure motor hemiparesis
      and 68 (13%) patients with sensorimotor stroke. RESULTS: Computed tomography or
      autopsy was compatible with a lacunar stroke (ie, detection of a lacune or
      permanently negative computed tomography) in 170 (33%) patients, of whom 123
      (72%) had pure motor hemiparesis and 47 (28%) had sensorimotor stroke. This led
      to a sensitivity of 72%, a specificity of 72%, a positive predictive value of
      56%, and a negative predictive value of 84%. Overall positive predictive value of
      pure motor hemiparesis was 58% (60% for two areas and 58% for three areas
      involved), and that of sensorimotor stroke was 51% (87% for two areas and 40% for
      three areas involved). By separately evaluating the sides of lesions, we found a
      positive predictive value of 46% for right-side infarcts and of 72% for left-side
      infarcts. Right-side lesions constituted 51% of lesions in lacunar syndrome
      patients with lacunar stroke, 76% in those with nonlacunar stroke, 19% in
      nonlacunar syndrome patients with lacunar stroke, and 31% in those with
      nonlacunar stroke (P < .0001). During the first days of hospital stay we observed
      a deterioration of 21% of lacunar syndrome patients with nonlacunar stroke and an
      improvement of 49% of nonlacunar syndrome patients with lacunar stroke, with
      appearance and disappearance of symptoms of cortical involvement, respectively.
      The examination of these patients after the occurrence of these clinical changes
      would have led to a daily increase of the positive predictive value up to a
      maximum of 66% at day 7. CONCLUSIONS: Pure motor hemiparesis and sensorimotor
      stroke diagnosed within 12 hours of the event are poorly predictive of lacunar
      strokes. Hence, the very early identification of these syndromes cannot be used
      for patient selection in therapeutic trials.

PMID- 8266390
TI  - Silent infarction in acute stroke patients. Prevalence, localization, risk
      factors, and clinical significance: the Copenhagen Stroke Study.
AB  - BACKGROUND AND PURPOSE: Our objective was to study age-specific prevalence,
      computed tomographic (CT) characteristics, risk factors, and the prognostic
      influence on stroke outcome of silent infarction in acute stroke patients.
      METHODS: The study was prospective and community-based and included 801 acute
      stroke patients, of whom 587 had first-ever stroke. A CT scan was performed in
      500 (85%) of the 587 patients with first-ever stroke. CT was reviewed blindly,
      and infarcts were classified according to patient history as silent or
      symptomatic. Patients were evaluated initially with the Mini-Mental State
      Examination (MMSE) and weekly with both the Scandinavian Stroke Scale (SSS) and
      the Barthel Index (BI) from the onset of stroke to completion of rehabilitation.
      CT characteristics, risk factors, and stroke outcome were compared in stroke
      patients with and without silent infarction. RESULTS: The prevalence of silent
      infarction in patients with first-ever stroke and recurrent strokes was similar,
      at 29% (group aged 0 to 54 years, 16%; 55 to 64 years, 22%; 65 to 74 years, 30%;
      75 years or older, 33%). Silent infarcts were small and subcortical. Independent
      risk factors were increasing age (odds ratio [OR], 1.95 per 25 years; confidence
      interval [CI], 1.19 to 3.15), hypertension (OR, 1.75; CI, 1.13 to 2.70),
      claudication (OR, 1.74; CI, 1.01 to 3.00), and male sex (OR, 1.72; CI, 1.12 to
      2.64); other stroke risk factors such as atrial fibrillation and former transient
      ischemic attack were not independent risk factors. Patients with and without
      silent infarction did not differ in frequency of prestroke home care (P = .2).
      MMSE (P = .56), initial BI (P = .62) and SSS score (P = .08), BI (P = .85) and
      SSS score (P = .75) after completion of rehabilitation, or in the speed of
      recovery (P = .85). Length of hospital stay, mortality rate, and discharge rate
      to nursing home also did not differ between the two groups. CONCLUSIONS: This
      community-based study shows that silent infarction in stroke patients is more
      related to certain stroke risk factors than others and that silent infarction
      does not seem to influence the prognosis of stroke.

PMID- 8266391
TI  - [The price of a complicated choice in care of the elderly].

PMID- 8266392
TI  - [Losing your way in the nursing home: spatial orientation from an architectural
      viewpoint. A review].
AB  - Many elderly with senile dementia living in an old people's home or nursing home
      have problems with spatial orientation and finding their way. The same holds true
      for confused and disturbed elderly who still live at home. To a large extent
      these problems result from cognitive and perceptual impairments. However, another
      important and often underestimated factor is the influence of the built
      environment. The design of many buildings and outdoor spaces offers insufficient
      environmental support for route-learning, route-finding and topographical memory,
      which promotes disorientation. Disorientation is enhanced by repetition of
      identical units, little differentiation in form, colour and material, and a lack
      of places with striking perceptual characteristics. This review of the literature
      on spatial orientation of the frail elderly focuses on dementia patients. It
      turns out that many guidelines can be offered to reduce spatial disorientation,
      such as a clear layout of the building, clear functions of spaces and places,
      adequate contrasts of forms and colours, personalization of places and
      application of the so called Gestalt Laws. However, empirical research to
      evaluate the effects of application of these guidelines is still scare.

PMID- 8266393
TI  - [Relations with nursing home residents with dementia: an exploratory study of
      behavior and behavioral determinants of caregiving personnel].
AB  - The number of demented old people in residential homes is increasing. The
      majority of the staff of these homes is not or insufficiently trained in dealing
      with demented people which may cause problems in daily practice. Staff behaviour
      and determinants of that behaviour associated with the management of demented old
      people, were examined with a questionnaire. The research took place in Maastricht
      and its surrounding area in July 1990 in eight residential homes with a total
      number of 136 responding attendants. The results give insight into changes that
      are necessary in order to align the staff's behaviour with recommendations for
      dealing with demented people. The behaviour of the respondents fits rather well
      with recommendations to activate demented people, to communicate with them and
      not to change anything around them. Respondents' behaviour that is not in
      agreement with the recommendations is correcting and testing of the demented
      elderly. Moreover, there is more correcting and testing when knowledge about the
      effects is less and when there is less support from colleagues on the
      inappropriateness of correcting or testing. Training the attending staff in
      dealing with dementia has a positive influence on knowledge about dementia and
      increases the provision of recommended care. A specific training in dealing with
      demented old people is recommended during and after the professional training of
      the staff.

PMID- 8266394
TI  - [Participants in movement programs for 55-year-olds and older. An exploratory
      study of 'More Movement for the Elderly' in Limburg].
AB  - In this article an exploratory study into a national exercise program for people
      of 55 years and older is reported. In order to gain more insight in the various
      characteristics of the participants, a questionnaire was completed by a sample of
      839 persons. The studied aspects are background characteristics, medical
      characteristics, characteristics of daily activities, risk behaviour, way of
      acquaintance with and motive for participation in the program. The results of the
      research are, if possible, compared with a reference group. A comparison between
      the participants of the various types of the movement program, shows similarities
      on the dimensions ADL-problems and bad health. Differences are found on the
      dimensions gender, age and education. The conclusion is that the choice of the
      type of the movement program is probably made on the ground of these three
      characteristics. The comparison between the participants of the exercise program
      and the reference group shows that a selection within the population of people of
      55 years and older is very likely. The majority of the participants is 65 to 74
      years old (43%), female (80%) and of low educational level (85%). Positive
      differences in favour of the exercise participants are found on the variables
      hypertension, medicine usage. ADL problems and risk behaviour (smoking and
      drinking). It is, however, unclear whether these differences are the result of an
      effect of the program or the result of selection in the program population. A
      combination of these two factors is also not ruled out. An effect-study can give
      more evidence for one of the factors involved.

PMID- 8266395
TI  - Immunoassays for tropical parasitic infections.

PMID- 8266396
TI  - Chemotherapy of leprosy--current status and future prospects.
AB  - The introduction of multi-drug therapy (MDT) by the World Health Organization in
      1982 has proved to be the most important advance in the management and control of
      leprosy since the first use of the sulphone drugs 40 years earlier. For the first
      time, the number of registered leprosy cases has shown a decline from a peak of
      5.37 million in 1985 to 3.1 million in February 1992. The 2 standard MDT regimens
      have proved simple to apply in most parts of the world, are relatively cheap,
      generally acceptable, and have shown remarkably few toxic side-effects.
      Nevertheless, difficulties have arisen in distinguishing between multibacillary
      and paucibacillary leprosy, especially when skin smears are of poor quality.
      Relapses in paucibacillary leprosy have proved difficult to distinguish from late
      reversal reactions. In multibacillary leprosy, the duration of treatment, 2-10
      years in lepromatous leprosy, is a source of difficulty, and in addition light
      skinned patients dislike the skin discolouration caused by clofazimine, for fear
      that their diagnosis might be discovered. The discovery that 3 different groups
      of drugs are highly bactericidal for the leprosy bacillus, although not so
      rapidly bactericidal as rifampicin, raises the possibility of having simplified,
      shorter, or better supervised regimens in the future as second generation MDT.
      These drugs include the 4-fluoroquinolones, pefloxacin, ofloxacin and
      sparfloxacin, the tetracycline minocycline, and the macrolide clarithromycin.
      Finally, in low-prevalence areas it is opportune to consider chemoprophylaxis and
      immunoprophylaxis for child contacts of lepromatous patients.

PMID- 8266397
TI  - The microbiology of Mycobacterium leprae; progress in the last 30 years.
AB  - Over the last 30 years, there have been dramatic changes in the way Mycobacterium
      leprae is studied in the microbiology laboratory. The organism still has not been
      grown in vitro but, starting with demonstration of growth in the footpads of mice
      and culminating in the application of molecular biological and genetic
      techniques, we are now in a position to circumvent some of the difficulties
      arising from lack of cultivability. Such studies are providing us with new
      insights into the basic biology of the organism and are likely to provide new
      tools which will be of value in the clinical laboratory. In this article, I
      briefly outline the progress which has been made, and the potential applications
      of molecular techniques in such areas as bacterial identification and drug
      resistance testing.

PMID- 8266398
TI  - Immunology of leprosy.
AB  - The host immune response to Mycobacterium leprae is critical for control of the
      infection but also responsible for the immunopathological damage to skin and
      nerves. The complex and varied immune responses to the organism are the basis for
      the clinical spectrum of disease ranging from tuberculoid to lepromatous leprosy.
      The cellular interactions underlying this spectrum are discussed and the
      antigenic components of the bacillus briefly reviewed. M. leprae has evolved a
      variety of mechanisms to avoid macrophage bactericidal mechanisms. These result
      in the persistence of bacilli and the release of cytokines leading to chronic
      granulomatous inflammation. The immune response to M. leprae is dynamic and
      spontaneous variations in cellular reactivity occur with time leading to type I
      and II leprosy reactions. The factors which preset the host immune response to a
      tuberculoid or lepromatous pattern and which precipitate reactional episodes
      remain to be elucidated.

PMID- 8266399
TI  - Epidemiology and control of leprosy--a review of progress over the last 30 years.
AB  - A review of progress in the epidemiology and control of leprosy indicates that,
      even though there has been only limited advancement in the epidemiological
      understanding of the disease, control of leprosy through chemotherapy of patients
      has been highly successful. Diagnostic tools using serology and other means have
      substantially improved, particularly in meeting research needs. There has been a
      reduction of more than 50% over the past decade in the leprosy case load in the
      world, due mainly to the vigorous implementation of multidrug therapy (MDT) in
      the treatment of the disease. MDT has been remarkably effective in curing
      patients, preventing relapse and minimizing side-effects. The progress in disease
      control in recent years prompted the World Health Assembly in 1991 to endorse a
      goal of global elimination of leprosy as a public health problem by the year
      2000, defining elimination of leprosy as attaining a level of prevalence below
      one case per 10,000 population. The future prospects for leprosy control in
      general and improved MDT appear to be good.

PMID- 8266400
TI  - Case studies from the biomedical and health systems research activities of the
      Swiss Tropical Institute in Africa.
AB  - Neither high theoretical efficacy of disease control tools, nor diagnostic
      accuracy, nor good compliance, nor adequate coverage can lead on its own to the
      final goal of community effectiveness. There is a complex relationship between
      these factors. The different steps in the process leading to effective health
      care in the community are discussed on the basis of biomedical and health systems
      research activities of the Swiss Tropical Institute. Schistosomiasis and malaria
      control provide the background to problems related to the efficacy of tools. In
      particular, information on the trial of a malaria vaccine candidate (SPf66) is
      given. Approaches to the rapid, accurate and economical diagnosis of communities
      at risk are discussed with reference to Schistosoma haematobium and S. mansoni.
      Health service support projects in Tanzania and Chad are presented to exemplify
      problems linked to the compliance of users/providers and coverage. Finally, it is
      shown that community effectiveness depends on the highest possible success rate
      for each step. This requires the co-operative efforts of all those involved: the
      scientist, the manager, the community health worker and, last but not least, the
      community itself.

PMID- 8266401
TI  - Effects of a hurricane on growth and morbidity in children from low-income
      families in Kingston, Jamaica.
AB  - This is the first report of the effects of a hurricane on children's health and
      nutritional status in which data were available preceding and following the
      event. When Hurricane Gilbert struck Jamaica in 1988, a longitudinal study was in
      progress in which children's weights and heights were recorded every 2 months and
      their morbidity histories taken every week. The investigation included 127
      stunted (low height-for-age) and 32 non-stunted children aged 23-44 months,
      living in poor areas of Kingston. The data from the 4 months before and after the
      hurricane were compared. There was an increase in the occurrence of respiratory
      symptoms including rapid or difficult breathing (P < 0.04), coughs (P < 0.001)
      and nasal discharges (P < 0.001) during the first 2-month period after the
      hurricane. However there was no significant effect on the occurrence of diarrhoea
      and injuries. Deficits were also found in height gain (P < 0.001) during the same
      period. These adverse effects were found in spite of the large amount of food aid
      received and the aggressive health education programme implemented after the
      hurricane.

PMID- 8266402
TI  - Haemorrhagic fever virus activity in equatorial Africa: distribution and
      prevalence of filovirus reactive antibody in the Central African Republic.
AB  - Seroepidemiological surveys were conducted to determine the frequency and
      distribution of haemorrhagic fever virus (HFV) activity in the Central African
      Republic. Human serum specimens (4295) were collected from 5 ecologically
      distinct zones. Serological evidence of HFV activity was found in all the zones.
      The filovirus antibody prevalence (24.4%, 1051/4295) was greater than the
      combined prevalence for Lassa virus, Rift Valley fever virus and Crimean-Congo
      HFV antibody (1.1%, 45/4295; P < 0.01). Evidence of filovirus activity was found
      in all zones: 21.3% (914/4295) of the population were seropositive for Ebola
      virus antibody while only 3.2% (137/4295) were seroreactive with Marburg viral
      antigens. Age and sex were important host-related factors influencing filovirus
      activity, particularly in dry grassland and moist forest communities. These
      communities shared many factors, but differences, such as agricultural practices
      and ethnic backgrounds, may also affect the risk of infection. Filovirus
      infections appear to occur without apparent disease. Continued investigations are
      needed to evaluate the true pathogenicity of the African filoviruses and the
      likelihood that unidentified serologically cross-reacting and non-pathogenic
      members of the filovirus family are active in equatorial Africa.

PMID- 8266403
TI  - Filovirus activity among selected ethnic groups inhabiting the tropical forest of
      equatorial Africa.
AB  - Seroepidemiological surveys were conducted to determine the frequency and
      distribution of filovirus activity among selected ethnic groups inhabiting the
      tropical forests of the Central African Republic. 427 serum specimens were
      collected from hunter-gatherers and subsistence farmers living in forest environs
      in the Lobaye District south of the river Lobaye and west of the river Oubangui.
      Striking serological evidence for filovirus activity was found in both
      populations. Ebola virus appears to be the most active filovirus; 17.6% (75/427)
      of the Lobaye survey population were seropositive for Ebola virus reactive
      antibody while 1.2% (5/427) were seroreactive with Marburg viral antigens. Ethnic
      background appeared to be an important risk factor influencing filovirus exposure
      in the forest communities. The filovirus antibody prevalence among 21-40 years
      old male Aka Pygmy hunter-gatherers was significantly (P = 0.03) 3 times higher
      (37.5%) than that in similarly aged male Monzombo and Mbati subsistence farmers
      (13.2%). Continued epidemiological investigations are needed to define ethnic
      related events influencing human filovirus activity in the Congo basin of
      equatorial Africa.

PMID- 8266404
TI  - Population-based study of serum hepatitis B virus DNA in Gabon.
AB  - The prevalence of serum hepatitis B virus (HBV) deoxyribonucleic acid (DNA) was
      measured in a Gabonese community at high risk for HBV infection. Among 698
      subjects 5 to 24 years old, the prevalence of HBsAg was 11.1% vs. 57.9% for anti
      HBs and 7.2% for anti-HBc alone. The prevalence of HBeAg among HBsAg-positive
      subjects was 26.5% vs. 59.5% for anti-HBe. The prevalence of HBV DNA tested by a
      hybridization spot test was 2.1% in the overall population and 18.7% among HBsAg
      positive subjects. HBV DNA was found in 15 of 21 HBeAg-positive subjects but in
      none of the subjects positive for anti-HBe or negative for both HBeAg and anti
      HBe. HBV DNA was not detected in any HBsAg negative subjects. The prevalence of
      HBV DNA decreased with age. This low prevalence of HBV DNA contrasts with the
      high level of endemicity in the study population.

PMID- 8266405
TI  - Evaluation of benzothiocarboxypurine for malaria diagnosis in an endemic area.

PMID- 8266406
TI  - Evaluation of the efficacy of Iran leishmanin and comparison with leishmanins
      from Wellcome (UK) and Roma (Italy) in cured cutaneous leishmaniasis patients.

PMID- 8266407
TI  - Possible role of an adrenal parasite reservoir in the pathogenesis of chronic
      Trypanosoma cruzi myocarditis.
AB  - The possible contribution of parasitism of the central vein of the adrenal gland
      (CVAG) to chronic Trypanosoma cruzi myocarditis was assayed by comparing the
      occurrence of nests of amastigotes in the left ventricular myocardium (LVM) and
      determining the number and extent of areas of focal leucocyte exudate (FLE) in
      Chagas disease patients with and without CVAG parasitism. The frequency of
      occurrence of T. cruzi nests in the LVM, as well as the FLE number and area, were
      greater among patients with CVAG parasitism. We therefore suggest that CVAG
      parasitism plays a role in the onset and intensity of chronic T. cruzi
      myocarditis.

PMID- 8266408
TI  - Laboratory infection with Schistosoma mansoni.

PMID- 8266409
TI  - An ultrasonographic study of liver fibrosis in patients infected with Schistosoma
      mansoni in north-east Brazil.
AB  - Between August 1988 and July 1990, 176 patients with Schistosoma mansoni
      infection attending the University Hospital, Recife, Brazil received a complete
      clinical examination including stool examination for intestinal parasites, liver
      function tests, and ultrasonography. The majority were also examined by upper
      digestive tract endoscopy. The clinical distribution of their disease was as
      follows: 26.7% intestinal, 13.6% hepato-intestinal, 53.4% compensated
      hepatosplenic and 6.3% decompensated hepatosplenic. Infection intensity was high,
      with a median of 360 eggs/g of faeces. Ultrasonography showed a good correlation
      between the degree of hepatic periportal fibrosis and the clinical stage of
      disease (P < 0.0001). Of the patients with the intestinal form of
      schistosomiasis, 12.8% had grade I fibrosis and the others had no fibrosis; 33.3%
      of patients with hepatointestinal schistosomiasis had grade I fibrosis, 8.3% had
      grade II fibrosis, and 58.4% had no fibrosis; all the patients with hepatosplenic
      disease had grade II or grade III fibrosis. The degree of liver fibrosis detected
      by ultrasonography correlated with the degree of oesophageal varices detected by
      endoscopy (P = 0.0001). The degree of oesophageal varices also correlated with
      the presence of haemorrhage (P < 0.0001). Ultrasonography is considered superior
      to liver biopsy, permitting a dynamic approach to the study of schistosomiasis
      morbidity with precise diagnosis and simple sequential follow-up of post
      treatment results.

PMID- 8266410
TI  - Leprosy, Kaposi's sarcoma and the acquired immunodeficiency syndrome in two
      African patients.

PMID- 8266411
TI  - Bacteraemia and meningitis among hospital patients with diarrhoea.
AB  - To characterize bacteraemia and meningitis in diarrhoeal patients, the records of
      3395 blood cultures and 120 cerebrospinal fluid (CSF) cultures from 6132 patients
      admitted with diarrhoea to the Clinical Research Centre of the International
      Centre for Diarrhoeal Disease Research, Bangladesh during 1989 were analysed.
      Microorganisms were isolated from 12% (417 of 3395) of blood cultures and 9% (11
      of 120) of CSF cultures. Children below 5 years of age represented 80% of all
      patients who had blood cultures and 82% of those who had CSF cultures made. The
      nutritional status was significantly lower in patients who had positive blood
      cultures than in those who had negative cultures. 23% (97 of 417) of patients
      with positive blood cultures and 45% (5 of 11) with positive CSF cultures died.
      Deaths occurred twice as often among patients who had organisms isolated than
      among those who had no organisms isolated from blood cultures. The organisms
      isolated from blood cultures which predicted most deaths were Pseudomonas
      aeruginosa, Neisseria meningitidis, Escherichia coli and Klebsiella sp., and they
      were multiresistant. We conclude that bacteraemia and meningitis remain serious
      complications associated with diarrhoea, especially in malnourished children; the
      therapeutic problem is further complicated by multiple drug resistance of the
      isolates.

PMID- 8266412
TI  - An open randomized comparative study of intramuscular artemether and intravenous
      quinine in cerebral malaria in children.
AB  - We have compared a multi-dose intramuscular regime of artemether against the
      standard intravenous quinine treatment for cerebral malaria in an open randomized
      study. Parasite clearance time, fever clearance time, and time to recover from
      coma were similar in the 2 groups of patients. Although the mortality rate was
      lower in the artemether group, the difference was not statistically significant.
      There was no toxic reaction of note in the artemether group. We therefore
      conclude that, because of its ease of administration and good toxicity profile,
      artemether is more suited for use in the rural regions of malaria endemic areas,
      where monitoring facilities may be minimal, compared to quinine which is
      potentially toxic.

PMID- 8266413
TI  - Antimonial treatment of hamsters infected with Leishmania (Viannia) panamensis:
      assessment of parasitological cure with different therapeutic schedules.
AB  - The objective of the study was to establish the effective dose and route of
      administration of Glucantime for treating hamsters infected with Leishmania
      (Viannia) panamensis and to use this method to test new treatment regimens to
      attain clinical and parasitological cure. In the first experiments animals were
      inoculated subcutaneously in the hind foot with 5 x 10(6) promastigotes of L.
      panamensis (HOM/COL/84/1099) from a 6 d culture. One month after inoculation,
      Glucantime was administered intramuscularly (i.m.) at 20, 40 or 60 mg/kg/d for 20
      d to groups of hamsters. Only 60 mg/kg/d resulted in both clinical improvement
      and parasite elimination from the skin and draining lymph node. In the second set
      of experiments, i.m., local and combined antimonial regimens were compared. The
      local regimen, of 4 intralesional (i.l.) injections of 4 mg of antimony at 5 d
      intervals, and the combined regimen (i.m. and i.l.), were more efficient at
      clearing parasites than the systemic (i.m.) schedule, especially when a low
      dosage of Glucantime (30 mg/kg/d x 20 d) was used. The results suggest that
      combining local treatment and low systemic dosages of antimonials results in
      clearance of L. panamensis.

PMID- 8266414
TI  - A population dynamic approach to the cost-effectiveness analysis of mass
      anthelmintic treatment: effects of treatment frequency on Ascaris infection.
AB  - This study examines the cost-effectiveness of different frequencies of mass
      chemotherapy in reducing helminth infection and morbidity at the community level.
      The cost-effectiveness framework utilities a dynamic model of helminth
      transmission which permits the effectiveness of treatment to be expressed as some
      long-term reduction in infection and disease. Cost analysis is incorporated into
      this framework using an itemized cost menu and cost data from an actual control
      programme. The cost-effectiveness of mass treatment is investigated using
      epidemiological measures considered appropriate to Ascaris lumbricoides infection
      in both a high and low transmission area. The optimal strategy for control is
      shown to be dependent on the control objectives, the rate of transmission, and
      existing budget constraints. The analysis suggests that if the aim of control is
      to reduce morbidity due to ascariasis and mass treatment is the approach
      selected, then it is more cost-effective to intervene in a high transmission area
      than in a low transmission area, and that relatively long intervals between
      treatments offer the most cost-effective strategy.

PMID- 8266415
TI  - Short course albendazole treatment for neurocysticercosis in Columbia.
AB  - The efficacy of albendazole was evaluated in 20 Colombian patients with
      neurocysticercosis showing neurological symptoms. All had parenchymal non
      enhancing cystic images by computerized tomography and a positive enzyme-linked
      immunosorbent assay for cysticercus antibodies in serum or cerebrospinal fluid.
      They stayed in hospital for 8 d during treatment with albendazole, 15 mg/kg/d in
      2 divided doses, and were then followed for at least 6 months after treatment.
      The number of cysts was reduced by 50% after 6 months. In 7 (35%) all cysts
      disappeared, in 7 (35%) the number was reduced, and in the remaining 6 (30%) the
      number was unchanged. In the 13 patients who still had cysts at 6 months, 11
      showed a moderate decrease in average cyst size and in 2 the size was unchanged.
      Side effects during treatment were observed in 60% of the cases, but only 3
      required corticosteroids.

PMID- 8266416
TI  - Serological diversity of antigens expressed on the surface of erythrocytes
      infected with Plasmodium falciparum.
AB  - We have studied the surface-antigen phenotypes of infected erythrocytes from
      children with acute falciparum malaria in the Punjab, Pakistan. Infected
      erythrocytes from 15 children and their homologous acute and convalescent sera,
      as well as hyperimmune sera from adults living in the same area, were used to
      analyse the serological diversity of parasite-associated antigens expressed on
      the surface of erythrocytes infected with Plasmodium falciparum. Analysis
      included agglutination, cytoadherence/inhibition of cytoadherence to melanoma
      cells, and rosette formation/disruption of rosettes formed between infected and
      non-infected erythrocytes. We found that isolate-specific antibodies were
      acquired by all children during convalescence and that there was a high degree of
      diversity of surface-antigen phenotypes. A majority of the sera either acquired
      or increased by 2- to 3-fold the capacity to inhibit cytoadherence and/or
      agglutinate the patient's own infected erythrocytes during convalescence and a
      strong correlation was found between these 2 activities. Hyperimmune sera from
      adults agglutinated and/or inhibited cytoadherence of many, but not all, of the
      isolates. Rosette formation was observed in 11 of the 15 isolates; 38% of the
      acute and 75% of the convalescent sera had anti-rosette activity on rosettes
      formed by the patient's own parasites. Among the isolates there was no
      correlation between rosette formation and binding of infected erythrocytes to
      melanoma cells. Our data provide good evidence that the children developed
      isolate-specific antibodies during convalescence from an acute attack of
      falciparum malaria and suggest that there was a high degree of heterogeneity of
      antigens expressed on the surface of infected erythrocytes.

PMID- 8266417
TI  - Antischistosomal vaccines: beyond the laboratory.
AB  - In the effort to develop vaccines against schistosomiasis, insufficient attention
      has been given to the field evaluation of their safety and efficacy, and to
      conditions of routine use. Evaluation demands a clear case definition and precise
      diagnostic tools to determine the number, condition, and pathological effects of
      the schistosomes present in each subject. These are difficult to achieve for
      schistosomiasis. The trial should also assess the reduction in community
      transmission attributable to immunization. Ethical problems in efficacy trials
      include the need for subjects to be exposed to infection when means are available
      to minimize it, and the need to define the point at which chemotherapy must be
      given to subjects found to be infected. The epidemiological and economic
      consequences of vaccine use must be compared with alternative methods of control
      and with natural low-level transmission in the community. The characteristics of
      a desirable vaccine should be defined in advance by modelling and/or a consensus
      development process to provide guidance to bench researchers and to identify
      those candidate vaccines that should advance to field trials.

PMID- 8266418
TI  - Immune response to rabies vaccine in Alaskan dogs: failure to achieve a
      consistently protective antibody response.
AB  - Previous studies in Thailand and Tunisia have shown that one injection of dog pre
      exposure rabies vaccine does not produce a lasting antibody titre in a
      significant group of animals. We therefore duplicated the Thai study in a small
      North American community using healthy, owned dogs. A tissue culture vaccine of
      known high antigenicity was given intramuscularly as one primary injection and
      antibody titres were determined by the rapid fluorescent focus inhibition test on
      days 14, 30, 60, 180 and 360. Titres were less than 0.5 i.u./mL in 27% of dogs
      bled at 2 months, 24% at 6 months, and in 33% one year after the primary
      vaccination. In rabies endemic regions, it may be hazardous to rely on the
      previous vaccine history of a biting dog when making post-exposure management
      decisions. A retrospective study of antibody levels in previously vaccinated dogs
      in North America also indicated that a single injection of vaccine often failed
      to result in adequate titres.

PMID- 8266419
TI  - Antioxidant vitamins in acute malaria.

PMID- 8266420
TI  - Human cutaneous leishmaniasis caused by Leishmania donovani s.l. in Kenya.
AB  - Our laboratory is characterizing Leishmania stabilates and isolates from active
      leishmaniasis cases. Smears and cultures from aspirates made on different dates
      from a single lesion on the bridge of the nose of an 18 years old Kenyan male
      from Nyandarua District contained Leishmania. The isolates, NLB-271 and NLB-271
      IA, were characterized by cellulose acetate electrophoresis (CAE) using 20 enzyme
      systems and by Southern analysis using 2 deoxyribonucleic acid (DNA) probes
      (pDK10 and pDK20) from a Dakar strain of L. major (MHOM/SN/00/DK1) and a third
      probe, p7-059 from L. infantum strain ITMAP-263. Digestion of the two Leishmania
      DNAs with endonucleases HindIII and PstI, followed by hybridization with the 3
      probes, revealed DNA fragment banding patterns indistinguishable from those of
      the L. donovani species complex. The CAE isoenzyme profiles of these 2 Kenyan
      isolates were indistinguishable from those of Kenyan L. donovani strains we
      designated as zymodeme Z6. Excluding post-kala-azar dermal leishmaniasis, this
      constitutes the first human case of cutaneous leishmaniasis caused by L. donovani
      s.l. in Kenya. Previously, cutaneous leishmaniasis cases in Kenya have been due
      to L. aethiopica, L. major and L. tropica only.

PMID- 8266421
TI  - Visual assessment of sporozoite ELISA results is as reliable as a plate reader in
      determining infection rates in field samples of Anopheles gambiae s.s.

PMID- 8266422
TI  - Lutzomyia verrucarum can transmit Leishmania peruviana, the aetiological agent of
      Andean cutaneous leishmaniasis.
AB  - In much of the endemic area for cutaneous leishmaniasis (uta) in the Peruvian
      Andes, the only 2 anthropophilic sandfly species present are Lutzomyia peruensis
      and Lu. verrucarum. On the basis of a single confirmed isolation of Leishmania
      peruviana (the aetiological agent of uta) from a wild Lu. peruensis, and apparent
      associations between sandfly abundance and the incidence of uta, it is generally
      believed that Lu. peruensis is the most important vector. In this paper, a
      potential role for Lu. verrucarum in the transmission of uta is indicated by
      laboratory experiments which show that this species is vectorially competent for
      L. peruviana. Individual or pooled colonized sandflies were permitted to take a
      second blood meal on 22 susceptible golden hamsters at varying intervals after
      feeding on hamsters previously infected with L. peruviana. Transmission was
      achieved by a single infected sandfly (of a total of 59) following a 15 d
      incubation period. Transmission was recognized by the characteristic clinical
      response (footpad swelling) associated with hamsters which have been inoculated
      with L. peruviana, and by the presence of parasites in aspirates made from the
      swollen footpad, detected by the polymerase chain reaction (PCR) and by parasite
      isolations in biphasic blood-agar culture medium. The identity of the parasite
      isolates was also confirmed by PCR (specific for parasites in the L. braziliensis
      complex). This is the first reported experimental transmission of L. peruviana by
      any sandfly species.

PMID- 8266423
TI  - Spleen puncture for the diagnosis of visceral leishmaniasis.

PMID- 8266424
TI  - Resolving the conflict in traditional ethics which arises from our demand for
      organs.

PMID- 8266425
TI  - Combined team effort in liver procurement and transplantation: 5-year experience
      of one organ procurement organization.
AB  - Combined team effort in liver procurement and transplantation has proven to be
      very advantageous as compared to same team effort in our experience. The
      incidence of primary nonfunction was almost identical between the two groups. We
      recommend that a combined team effort be used in liver transplantation to
      conserve the resources and ensure the safety of the transplant team. The practice
      of only a single local recovery team for all abdominal organ procurement should
      be encouraged.

PMID- 8266426
TI  - Discontinuing of a permanent information and education program among donor ICUS
      leads to a 50% decrease of organ donor rates.

PMID- 8266427
TI  - Transplant group management: a new concept in organ and tissue procurement.

PMID- 8266428
TI  - Attitudes and organ donor referral behavior of hospital staff.

PMID- 8266429
TI  - Advanced international training course on transplant coordination.

PMID- 8266430
TI  - Rat small bowel preservation for 24 and 48 hours.

PMID- 8266431
TI  - Effect of pretransplant flushout of the liver with a solution containing albumin
      on survival and organ function.

PMID- 8266432
TI  - Enhanced resistance to the effects of normothermic ischemia in kidneys using
      pulsatile machine perfusion.

PMID- 8266434
TI  - University of Wisconsin solution containing 2,3-butanedione-monoxime extends
      myocardium preservation time.

PMID- 8266433
TI  - Beneficial effect of machine perfusion on the preservation of renal
      microcirculatory integrity in ischemically damaged kidneys.

PMID- 8266435
TI  - Which organ preservation solution best protects vascular endothelium?

PMID- 8266436
TI  - Forty-eight-hour liver preservation and subsequent testing of isolated
      hepatocytes: an evaluation of University of Wisconsin vs M-400 solutions.

PMID- 8266437
TI  - Cold storage solutions for liver preservation.

PMID- 8266438
TI  - Effect of adenosine and allopurinol on liver ischemia-reperfusion.

PMID- 8266439
TI  - Pentoxifylline inhibits production of superoxide anion and tumor necrosis factor
      by Kupffer cells in rat liver preservation.

PMID- 8266440
TI  - Role of endothelin in orthotopic canine heart transplantation.

PMID- 8266441
TI  - Impact of donor factors and preservation on function and survival after liver
      transplantation.

PMID- 8266442
TI  - Preservation of human small intestine: function of smooth muscle and nerve.

PMID- 8266443
TI  - Can adenine nucleotides predict primary nonfunction of the human liver homograft?

PMID- 8266444
TI  - Hemodynamic and metabolic effects of substitutive triiodothyronine therapy in
      organ donors.

PMID- 8266445
TI  - Lung preservation with glucose-insulin-potassium: a solution for developing
      countries?

PMID- 8266446
TI  - University of Wisconsin solution for myocardial protection in heart
      transplantation--a comparison with HTK.

PMID- 8266447
TI  - HLA-DR mismatching in cadaveric kidney transplantation minimized through organ
      sharing for 1000 consecutive transplants.

PMID- 8266448
TI  - Organ sharing based on HLA matching saves dialysis years and patient lives.

PMID- 8266449
TI  - Survival of serologically HLA typed and matched cadaveric kidney transplants and
      patients: influence of serologic retyping of donors.

PMID- 8266451
TI  - Long-term success rate of HLA-DRB1 compatible kidney transplants.

PMID- 8266450
TI  - Omit HLA matching to attain shorter cold ischemic time?

PMID- 8266452
TI  - Impact of HLA DR typing by polymerase chain reaction amplification with DR beta 1
      sequence-specific primers on cadaveric renal allocation.

PMID- 8266453
TI  - Kidney allocation in the 1990s: progress and problems.

PMID- 8266454
TI  - "Transplant-euro-computer-network"--European initiative to support communications
      between transplant facilities.

PMID- 8266455
TI  - Costs for successful vs failed kidney transplantation: a two-year follow-up.

PMID- 8266456
TI  - Use of hepatitis C-positive donors in liver transplantation.

PMID- 8266457
TI  - HCV+ donors: should they be used for organ transplantation?

PMID- 8266458
TI  - Transmission of non-Hodgkin's lymphoma through renal allografts--disastrous
      result of false diagnosis and inadequate information.

PMID- 8266459
TI  - Possible effect of multiorgan procurement on organ donation.

PMID- 8266460
TI  - Pregnancy following kidney donation.

PMID- 8266461
TI  - Unrecognized health problems diagnosed during living donor evaluation: a
      potential benefit.

PMID- 8266462
TI  - Living-unrelated kidney transplantation: a real source in the cyclosporine era.

PMID- 8266463
TI  - New pulsatile perfusion method for non-heart-beating cadaveric donor organs: a
      preliminary report.

PMID- 8266464
TI  - Organ procurement from non-heart-beating donors by total body cooling.

PMID- 8266465
TI  - Multiorgan procurement from non-heart-beating donors by use of Osaka University
      cocktail, Osaka rinse solution, and the portable cardiopulmonary bypass machine.

PMID- 8266466
TI  - Use of in situ cooling and machine perfusion preservation for non-heart-beating
      donors.

PMID- 8266467
TI  - Donor age and graft outcome in cadaver renal transplantation.

PMID- 8266468
TI  - Pulsatile kidney perfusion for preservation and evaluation: use of high-risk
      kidney donors to expand the donor pool.

PMID- 8266469
TI  - Decreased numbers of cadaveric donors with traumatic injuries equals increasing
      donor age: a 6-year analysis.

PMID- 8266470
TI  - Impact of donor cause of death on renal graft function--a multivariate analysis
      of 1545 kidney transplants.

PMID- 8266471
TI  - Transplantation of "unsuitable" organs?

PMID- 8266472
TI  - Innovative ex vivo repair of organs for renal transplantation.

PMID- 8266473
TI  - Myocardial ischemia during experimental brain death.

PMID- 8266474
TI  - ABO-incompatible liver transplantation: a risk worth taking.

PMID- 8266475
TI  - Intrahepatic biliary lesions and ABO incompatibility after liver transplantation.

PMID- 8266476
TI  - Monoethylglycinexylidide clearance test: its role as a part of brain-dead donors'
      evaluation for liver transplantation.

PMID- 8266477
TI  - Donor impact on outcome of bladder-drained pancreas transplants.

PMID- 8266478
TI  - A computer model for improved cadaver kidney allocation.

PMID- 8266479
TI  - What do intensive care unit personnel think about organ donation? Opinion poll
      amongst transplant centers.

PMID- 8266480
TI  - Organ procurement: missing cases and their causes in a prospective study in
      Mexico.

PMID- 8266481
TI  - Donation/transplantation of organs: influences on the health worker.

PMID- 8266482
TI  - Population attitudes toward organ donation in Germany.

PMID- 8266483
TI  - Demand and supply of kidneys for transplantation in Poland.

PMID- 8266484
TI  - Donor detection and organ procurement in the Madrid region. Group of Transplant
      Coordinators of the Region of Madrid.

PMID- 8266485
TI  - Organ procurement in Spain: the importance of a transplant coordinating network.

PMID- 8266486
TI  - Number of potential cadaveric donors: reasons for nonprocurement and suggestions
      for improvement.

PMID- 8266487
TI  - Lung procurement in Mexico.

PMID- 8266488
TI  - Increasing organ donation at a large inner city public hospital.

PMID- 8266489
TI  - Influence of donor and recipient age on renal allograft survival time.

PMID- 8266490
TI  - Does diabetes insipidus in brain dead organ donors protect acute tubular necrosis
      in renal grafts?

PMID- 8266491
TI  - Effect of HLA matching on graft survival in live donor kidney transplantations.

PMID- 8266492
TI  - Long-term function of renal allografts from elderly donors: a prospective study.

PMID- 8266493
TI  - Living donor organ transplantation at our center.

PMID- 8266494
TI  - One-year transplantation activities in our center.

PMID- 8266495
TI  - Does donor age exclude liver grafting?

PMID- 8266496
TI  - Experiences with a simplified liver harvesting technique--single aorta in situ
      flush followed by portal back table flush.

PMID- 8266497
TI  - Impact of donor criteria on postoperative graft function in liver
      transplantation.

PMID- 8266498
TI  - Influence of marginal donors on early results after heart transplantation.

PMID- 8266499
TI  - Uniform standardized technique of donor liver removal irrespective of arterial
      anomalies.

PMID- 8266500
TI  - Organ procurement using abdominal cavity cooling after management of the brain
      dead donor: an experimental study.

PMID- 8266501
TI  - Intravenous administration of glycogen precursors in cerebrally dead swines.

PMID- 8266502
TI  - In vivo monitoring of myocardial interstitial neuropeptide tyrosine release
      following brain death.

PMID- 8266503
TI  - Optimization of in situ renal perfusion of non--heart-beating donors: four-lumen
      catheter developed for continuous perfusion pressure determination.

PMID- 8266504
TI  - Metabolic status of brain-dead patients managed for organ procurement.

PMID- 8266505
TI  - Myocardial revascularization in ischemic cardiomyopathy: a way for better donor
      heart allocation.

PMID- 8266506
TI  - Long-term follow-up of recipients of cadaver kidney allografts from elderly
      donors.

PMID- 8266507
TI  - Correlation between chilling-induced injury in human cells and phospholipid
      membrane phase transition.

PMID- 8266508
TI  - Type I antifreeze protein attenuates cell recoveries following cryopreservation.

PMID- 8266509
TI  - Synergistic interaction of low-molecular-weight polyvinylpyrrolidones with
      dimethylsulfoxide during cell cryopreservation.

PMID- 8266510
TI  - Influence of whole heart postprocurement cold ischemia time upon cryopreserved
      heart valve viability.

PMID- 8266511
TI  - Prolonged liver cold ischemia time with University of Wisconsin solution and
      incidence of delayed graft function after hepatic transplantation: a single
      center experience.

PMID- 8266512
TI  - Opiate receptor blockade improves function and survival of high-risk renal
      allografts.

PMID- 8266513
TI  - Comparative effects of blood, colloid, and Ringer's lactate terminal allograft
      rinse on the results of orthotopic liver transplantation.

PMID- 8266514
TI  - Ultrastructural correlation of endomyocardial biopsy findings with myocardial
      preservation in human cardiac allografts.

PMID- 8266515
TI  - Comparison of intermittent injection with single-flush UW solution for donor
      heart preservation.

PMID- 8266516
TI  - Mediator clearing effects of rinse solution in lung preservation.

PMID- 8266517
TI  - New evaluation method for viability of mitochondria in liver graft using
      fluorescent dye.

PMID- 8266518
TI  - Relationship between superoxide dismutase activity of liver tissue and survival
      in swine liver transplantation.

PMID- 8266519
TI  - Improved renal preservation with PB-3 flush solution during 72 hours cold
      storage: demonstration of a salutary effect on isolated mitochondrial
      respiration.

PMID- 8266520
TI  - UW solution decreases Kupffer cell function in rat livers.

PMID- 8266521
TI  - Significance of terminal rinse for rat liver preservation.

PMID- 8266522
TI  - Improved grafted rat heart metabolic function using defibrotide.

PMID- 8266523
TI  - Platelet-activating factor as a vasodepressive mediator of liver ischemia.

PMID- 8266524
TI  - Severe tissue damage occurs during cold preservation of liver grafts.

PMID- 8266525
TI  - Effect of Carolina rinse solution in cultured rat sinusoidal endothelial cells.

PMID- 8266526
TI  - UW vs Euro-Collins solution in preserving warm ischemia-damaged kidneys.

PMID- 8266527
TI  - Viability loss of preserved liver grafts is not due to blood-flow disturbance.

PMID- 8266528
TI  - Hemodialysis improves results of pig liver perfusion after warm ischemic injury.

PMID- 8266529
TI  - Preparing heart valve allografts for endothelial cell seeding.

PMID- 8266530
TI  - Fate of endothelial cells during transport, cryopreservation, and thawing of
      heart valve allografts.

PMID- 8266531
TI  - Iberic organ sharing: analysis of an experience.

PMID- 8266532
TI  - Significance of HLA matching in renal graft allocation.

PMID- 8266533
TI  - Management of cytomegalovirus infection in high-risk recipients after renal
      transplantation: prophylaxis by hyperimmunoglobulins or DHPG treatment?

PMID- 8266534
TI  - Chagas' disease can be transmitted through kidney transplantation.

PMID- 8266535
TI  - Evolution of chagasic kidney transplant patients.

PMID- 8266536
TI  - Monitoring of donor sensitization in kidney transplant recipients by flow
      cytometric crossmatch.

PMID- 8266537
TI  - Genotyping analysis of HLA class II genes in donor-recipient kidney transplant
      pairs.

PMID- 8266538
TI  - Clinical value of HLA-DRB1 typing in cadaveric renal transplantation.

PMID- 8266540
TI  - Monitoring after transplantation in liver and kidney transplant recipients with
      anti-donor HLA antibodies.

PMID- 8266539
TI  - Incidence of a positive final antiglobulin (AHG) T-cell crossmatch in patients
      waiting for cadaveric renal transplantation is not influenced by race of
      recipient.

PMID- 8266541
TI  - Immune factors correlating with improved long-term graft outcome in kidney, lung,
      and heart transplants.

PMID- 8266542
TI  - Antidonor-HLA antibodies and soluble HLA antigens after kidney transplant.

PMID- 8266543
TI  - Prolonged survival of grafted rat hearts by use of defibrotide and cyclosporine.

PMID- 8266544
TI  - Prolonged survival of rat cardiac allografts induced by intrathymic injection of
      donor bone marrow cells.

PMID- 8266545
TI  - Preliminary reports from the New Liver Transplant Program at the University of
      Rome "Tor Vergata".

PMID- 8266546
TI  - Vascular reconstruction in 105 consecutive pancreas transplants.

PMID- 8266547
TI  - Biliary atresia: results of long-term conservative treatment and of liver
      transplantation.

PMID- 8266548
TI  - Interleukin-4 is a critical mediator of the effector phase of cell-mediated
      reactions.

PMID- 8266549
TI  - Antigen-specific production of lymphokines is influenced by the MHC/antigen
      complex presented to T lymphocytes.

PMID- 8266550
TI  - Pulmonary rejection diagnosis after lung and heart-lung transplantation.

PMID- 8266551
TI  - Comparison of liver ischemia-reperfusion models in the rat with and without
      jugular-mesenteric bypass.

PMID- 8266552
TI  - Preconditioning: effect upon lesion modulation in warm liver ischemia.

PMID- 8266553
TI  - Use of triiodothyronine replacement therapy to reverse donor myocardial
      dysfunction: creating a larger donor pool.

PMID- 8266554
TI  - Modern application for an old compound: 8-methoxypsoralen for photochemotherapy
      after heart transplantation.

PMID- 8266555
TI  - Present status of organ procurement, preservation, and sharing: a summation of
      the Second International Congress of the Society for Organ Sharing.

PMID- 8266557
TI  - Doxycycline sclerotherapy of lymphocele after renal transplantation and its
      inhibition of gelatinase activity.

PMID- 8266556
TI  - Frequent achievement of a drug-free state after orthotopic liver transplantation.

PMID- 8266558
TI  - Renal transplantation in patients with end-stage renal disease secondary to
      systemic lupus erythematosus.

PMID- 8266559
TI  - [The effect of a vaccinal strain of Yersinia pestis on lysosome fusion with
      phagosomes in peritoneal and alveolar macrophages].
AB  - It is established that the frequency of phagosome-lysosome fusion in alveolar
      macrophages is lower than in the peritoneal cells upon endocytosis of Yersinia
      pestis. The subcutaneous immunization activates the phagosome-lysosome fusion in
      peritoneal macrophages, whereas alveolar cells remain without change. The
      aerogenic vaccination stimulates this process in both peritoneal and alveolar
      macrophages, as distinct from subcutaneous immunization.

PMID- 8266560
TI  - [A preparative method for isolating the synaptonemal complexes from mammalian
      spermatocytes].
AB  - A method of isolation of synaptonemal complexes (SC) from mouse, rat and Syrian
      hamster spermatocytes is described. A fraction of pachytene spermatocyte nuclei
      was obtained by centrifugation of the testis homogenate in stepwise sucrose
      gradient and then lysed. The resulting chromatine was hydrolysed with DNAse II,
      and a fraction of isolated SCs was obtained by ultracentrifugation of the
      hydrolysate. The method can be applied for obtaining the SC fraction from
      spermatocytes sufficient for cytological, biochemical and molecular biology
      studies.

PMID- 8266561
TI  - [Changes in the cellular ultrastructure of the gill epithelium in Tilapia under
      the action of cadmium on the fish].
AB  - The ultrastructure of the Tilapia gill epithelium cells was studied under
      condition of a prolonged (2 months) treatment of these fishes with cadmium in a
      concentration of 5 mg/l. A decrease in the quantity of chloride cells in the
      primary gill epithelium, and of respiratory cells in the secondary epithelium was
      found. The chloride and mucous cells are, respectively, most sensitive and most
      resistant to the influence of cadmium. The accumulation of lysosomal structures
      in chloride and respiratory cells was observed, in addition to a reduced surface
      relief in these and some damage in mitochondria of the former being noticed. A
      slow development of reparation processes in the tilapia gill epithelium cells was
      followed after the cancellation of cadmium effect. No restoration of the original
      ultrastructural pattern of the gill epithelium cells was observed after a 1.5
      month inhabitance of Tilapia in clean water.

PMID- 8266562
TI  - [The effect of 1-isoproterenol on monovalent cation transport in activated human
      lymphocytes].
AB  - Potassium (rubidium) influx, sodium and potassium contents, as well as protein
      contents and 3H-thymidine incorporation have been investigated in quiescent
      lymphocytes, PHA-stimulated lymphocytes and T-lymphocytes, activated by human
      recombinant interleukin 2 (IL-2) within 0.5, 24 and 48 h. In quiescent
      lymphocytes ouabain-sensitive Rb+ influx was diminished by I-isoproterenol and
      forskolin. Both the cAMP elevating agents decreased the enhancement of ouabain
      sensitive and ouabain-resistant Rb+ influxes in PHA-stimulated lymphocytes in 24
      and 48 h. The IL-2 activation of T-cells during 24 and 48 h was accompanied by
      the elevation of Rb+ influxes and Ki content. L-isoproterenol inhibited ouabain
      sensitive Rb+ influx in activated T-cells. This inhibition was found to correlate
      with 3H-thymidine incorporation in cells. Thus, the effects of l-isoproterenol
      and forskolin on ionic transport in human activated lymphocytes correlated with a
      well-known cAMP inhibition of lymphocyte proliferation.

PMID- 8266563
TI  - [The effect of adrenal-regeneration hypertension on protein-nucleic acid
      metabolism in rat atrial cardiomyocytes].
AB  - A study was made on cardiomyocytes of the left atrium of rats with experimental
      arterial hypertension due to adrenal regeneration. The nuclear DNA and the total
      protein in the cytoplasm were revealed using two consecutive tests: the Feulgen
      reaction, and Naphthol yellow S staining. The two-wavelength scanning
      cytophotometry was used for measuring DNA and protein contents. It has been
      ascertained that the polyploidy level in the nuclei of the left atrium myocytes,
      measured 6 and 9 weeks after nephradrenalectomy, remained the same as in the
      intact animals. The increase in the share of tetra- and octaploid nuclei occurred
      by 12 weeks. The mean nuclear volume decreased gradually throughout 9 weeks and
      subsequently was seen to increase, but by 12 weeks it did not yet reach the
      control level. The cytoplasm volume decreased by 6 weeks, then started to
      increase by 9 weeks to reach almost the standard level. The common protein
      content in the atrial myocytes decreases also by 6 weeks, but restores more
      rapidly than the volume, and reaches the standard level by 9 weeks, exceeding the
      same by 12 weeks. Thus, the prolonged hyperfunction of the atrial cardiomyocytes,
      associated with arterial hypertension, results in their hypertrophy which becomes
      apparent both in the increased polyploidy and in the augmented protein mass of
      the cells.

PMID- 8266564
TI  - [The subcellular distribution of the glutathione system enzymes in the brain
      tissue of the rat].
AB  - Using the percoll density gradient method for rapid isolation of organelles the
      distribution of glutathione system enzymes in the rat brain was characterized
      including glutathione S-transferase (GST), glutathione peroxidase (GPx), and
      glutathione reductase (GR). In the fraction of mitochondria, the shares of GPx,
      GR, and GST were found to be as much as 92, 61, and 15% from their respective
      general activities. No enzymatic activity was found in lysosomes. Fractions of
      organelles with low density (microsomes, Golgi complex, cytoplasmic membranes)
      were cross-contaminated. Nevertheless, on the base of the established dynamics of
      distribution of the marker enzyme activity among various cell organelles it is
      suggested that, besides mitochondria, the glutathione system enzymes may be
      localized primarily in the endoplasmic reticulum, rather than in other
      organelles.

PMID- 8266565
TI  - [The heavy metal content in the soft tissues and shells of specimens of 3
      varieties of the Azov and Black Sea mussel Mytilus galloprovincialis].
AB  - In representatives of 15 micropopulations of the Black Sea mussels related to
      three varieties of Mytilus galloprovincialis var. dilatata, var. acrocyrta, var.
      frecviens the content of iron, zinc, lead, copper and cadmium in the soft tissues
      and shells has been determined with the use of atomic adsorption
      spectrophotometry. It has been found that of importance is the content of
      industrial wastes in the habitat of the micropopulation examined rather than its
      attribution to some or other variety. In representatives of all the varieties the
      accumulation of metals in soft tissues was higher than that is shells. By their
      concentration in tissues the metals examined can be aligned in the following row
      in decreasing order: iron, zinc, lead, copper and cadmium.

PMID- 8266566
TI  - [The production of clones of "man x Chinese hamster" hybrid cells containing
      different parts of the human genome].
AB  - Some approach has been described to create hybrid cell lines (human x Chinese
      hamster) which contain different parts of human genome, and then efficiently to
      reveal and isolate the human DNA from these. This method involves the
      introduction of a selective marker in different sites of the human cell genome,
      by transfecting them with plasmid SV2neo, and the use of flow cytometry and DNA
      polymerase chain reaction with primers specific only for human DNA.

PMID- 8266567
TI  - [The detection of human DNA in cell hybrids by the polymerase chain reaction with
      universal primers: the species specificity of the amplified DNA].
AB  - The human DNA detection method is developed on the basis of DNA cross
      hydridization of the amplification products obtained by the universally primed
      polymerase chain reaction (UP-PCR) technique. These PCR products are
      characterized by species-specificity in hybridization assay. Two somatic cell
      hybrids "human x Chinese hamster" supposed to contain the human DNA, according to
      selection procedure, were analysed by this method. As a result, the presence of
      human DNA, unable to be tested by cytological techniques, have been proven. The
      amplified human DNA can be mapped by this method.

PMID- 8266568
TI  - [The kinetics of the transition to DNA synthesis in the cell cycle of sister
      cells of the ESK line in culture].
AB  - The proliferation kinetics of a cultured pig embryo kidney cell line, PK, was
      studied by time lapse cinemicrography and 3H-TdR autoradiography. The duration
      and variability of all phases of the cell cycle was estimated. Evidence is
      presented that the variation in the cell cycle transit time of both unrelated and
      sibling cells results mainly from the variation in transit of G1-phase. These
      results indicate that the kinetics of the entry of cells into the S-phase
      represents the first order kinetics and does not contradict the transition
      probability model of cell cycle control. Analysis of the labeling pattern of
      sister cells reveals a clear correlation of the sister cells G1 transit time.

PMID- 8266569
TI  - [The adaptive response of B cells to the action of cytotoxic preparations in
      culture. II. Immunoglobulin interaction with adriamycin and ethidium bromide].
AB  - The binding of adriamycin and ethidium bromide coupled to sepharose beads with
      intracellular and serum immunoglobulins is detected. These drugs do not bind with
      Fab and Fc fragments of immunoglobulin. The binding of ethidium bromide to
      immunoglobulins is competitive. Possible adaptive features of this phenomenon are
      discussed.

PMID- 8266570
TI  - [The adaptive response of B cells to the action of cytotoxic preparations in
      culture. III. The possible mechanism of the action of adriamycin on immunoglobin
      synthesis by the cells of murine myeloma].
AB  - A dose-dependent stimulation of immunoglobulin synthesis by Spebr-5 cells in the
      presence of adriamycin is shown. This effect is significantly blocked in the
      presence of iron-chelating agent 2,2-bipyridine. Moreover, low doses of H2O2 and
      heat shock also caused enhancement of immunoglobulin synthesis. These data
      suggest the involvement of free radical processes in the adriamycin induced
      stimulation of immunoglobulin synthesis.

PMID- 8266571
TI  - [Changes in the population composition and the rates of proliferation and
      specialization of erythroid cells in rats with experimental anemia].
AB  - Cytomorphologic, morphometric and population analyses have revealed that during
      acute anemia, induced by phenylhydrazin, the proliferative activity of
      erythroblasts increases, an abrupt change in the structures of erythroid
      populations of both bone marrow and peripheral blood is observed, together with
      the increase in the rates of their specialization. Also, the ratio of the stem
      cells which differentiate by the erythroid pathway is increased, and the macro-
      and microcytosis mechanisms, which are essentially salient in normal conditions,
      are switched on. The roles of macro- and microcytes in the restoration of the
      normal amount of erythroid cells and haemoglobin contents in the blood are
      discussed.

PMID- 8266572
TI  - [Changes in the spatial organization and structure of the smooth-muscle cells of
      the tunica media of the major arteries during lengthwise stretching in situ].
AB  - It has been shown that in vivo stretching of the arterial wall leads to the loss
      of cell-cell contacts between medial smooth muscle cells (SMC), and to the change
      in the cell cooperation type. It is accompanied by the increase in SMC
      proliferative activity, and by changes in their shape and phenotype, from the
      contractile to the synthetic one. The increase in the number of extracellular
      connective tissue structures occurs in the intercellular space.

PMID- 8266573
TI  - [Differences in the protein kinase C activity in CHO-K1 cells and in clone cells
      of this line resistant to ethidium bromide].
AB  - Protein kinase C (PK C) activity in cells of two ethidium bromide (EB) resistant
      clones with different proliferating rates, derived from CHO-K1 cell line, was
      assayed. After selection in the presence of 1 mkg/ml EB cells of isolated clones
      acquired cross-resistance also to some unrelated drugs of different structure. It
      is shown that resistant cells after the first step of selection elevated PK C
      activity level in membrane fractions. Subsequent increase in resistance (from 1
      to 10 mkg/ml EB) led to a further elevated enzyme activity both in cytosolic and
      membrane fractions in cells of both variants. The effect of EB presence in
      cultural media on the enzyme activity was tested. EB at a subtoxic concentration
      was shown to cause an increased PK C activity both in cytosolic and membrane
      fractions from resistant cells sublines.

PMID- 8266574
TI  - [Synergism in the stimulating effect of transforming growth factor beta and
      insulin on the substrate-independent proliferation of the CHO-719 cell line].
AB  - Cells of line CHO-719 from the Chinese hamster ovary have no epidermal growth
      factor receptors. It was detected that these cells were significantly stimulated
      to proliferate in a semisolid culture medium containing 0.33% agar by
      transforming growth factor beta (TGF-beta) in combination with insulin. This
      effect was even more pronounced when the cells of line CHO-719, adapted to the
      growth in the presence of low concentration (3%) of fetal bovine serum, were
      used. TGF-beta and insulin utilized separately exerted no influence on the
      cellular growth.

PMID- 8266575
TI  - [Retinoic acid intensifies the suppression of the proliferation of K562 cells by
      phorbol ester].
AB  - The effect of forbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the
      growth of cultured human chronic promyelocytic leukemia (K562) cells has been
      studied using cells growing in a medium consisting of RPMI 1640 supplemented with
      10% fetal serum and with or without retinoic acid. All the used concentrations of
      TPA (100.0, 10.0, 1.0 and 0.1 ng/ml) cause the expected inhibition of
      proliferation of these cells. Moreover, a block of proliferation of K562 cells
      became stronger after cotreatment with TPA and retinoic acid, although this acid
      itself did not have any effect on proliferation and differentiation of K562
      cells.

PMID- 8266576
TI  - [Cellular orientation and form in the elastic-hyperplastic layer of the human
      aortic intima in the area of the ostia of the intercostal arteries].
AB  - Using the Hatcher monolayer method, it has been shown that the aortic intimal
      smooth muscle cells, disposed on the flow divider of an intercostal artery, have
      predominantly spindle-like shapes to be oriented perpendicularly to the long axis
      of the vessel. Unlike, in the proximal and lateral sites of the intercostal
      ostium the intima is represented by stellate cells lacking any orientation. These
      distinctions may be presumably determined by the irregular distribution of
      hemodynamic loading on the aortic intima in different regions around the ostium
      of an intercostal artery.

PMID- 8266577
TI  - [The effect of Mycoplasma contamination and decontamination with ciprofloxacin on
      the karyotypic structure of the Chinese hamster V-79 lung cell line].
AB  - Karyotypic variability was investigated for the Chinese hamster lung cell line V
      79, infected (contaminated) with a mycoplasma Acholeplasma laidlawii A. The
      mycoplasmal contamination did not affect cell distribution for the chromosome
      number. However, 30-70 days following cell culture contamination the increase in
      chromosomal aberrations was observed in the contaminated cell line primarily at
      the expense of chromosomal breaks. The following cyprofloxacin treatment of the
      culture resulted in mycoplasmal elimination and decrease in the frequency of
      chromosomal aberrations up to the control level. The analysis of G-banded
      chromosomes showed no significant differences in karyotypes of originally non
      infected cells and cells after decontamination. The karyotypic variability,
      induced by mycoplasmal infection in V-79 cell line, differed from that in the
      muntjac skin fibroblast cell line, the latter being described elsewhere. A
      predominant type of chromosomal variability in V-79 cell line are chromosomal
      breaks, whereas in the muntjac fibroblast cell line dicentrics (telomeric
      fusions) were primarily observed, possible explanations of these differences
      being discussed. This may be presumably due to differences in karyotypic
      structure of these two cell lines, and to their different adaptation to culture
      conditions.

PMID- 8266578
TI  - [The frequency of sister chromatid exchanges in preimplantation mouse embryos].
AB  - The frequency of sister-chromatid exchanges (SCE) was analysed in spontaneously
      and superovulated morulae and blastocyst of CBA, C57Bl, F1 CBA x C57Bl mice in
      culture with bromodeoxyuridine (BrdU). The background level for SCE was found to
      be 4-5 times higher in early embryos than in fetal or adult tissues of the mouse.
      The phenomenon of spontaneous sister-chromatid differentiation (SCD) of
      blastocyst chromosomes without any treatment with BrdU was observed. The SCE
      frequency was calculated on such chromosomes and was the same as with BrdU. A
      possible mechanism of this phenomenon is suggested.

PMID- 8266579
TI  - [The variability of the pattern of human G-band chromosomes in the late prophase
      early metaphase].
AB  - Original modification of the harvest procedure, hypotonic treatment and slide
      making techniques were used to obtain prometaphase spreads of good quality fitted
      to G-banding or to FISH. Human blood cultures were synchronized with a
      methotrexate block during synthesis, and following this with a thymidine release.
      Cells were then proceeded into prometaphase and early metaphase and were quickly
      harvested without exposure to colcemid. Following incubation in a mixture of
      0.56% KCl and 1% sodium citrate (1:1) for 20-23 min at room temperature, cells
      were fixed in 4 changes of fixative made of 3 parts of absolute methanol and 1
      part of glacial acetic acid. Three or four 100-105 microliters volume of a
      suspension of fixed cells were blew with a strength through pasteur pipette tip
      from a distance 5-6 cm onto chilled superclean slides wetted by water. These
      slides were then quickly flame dried. Prior to staining, prometaphase bearing
      spreads were held in thermostat overnight at 37 degrees C. Prometaphases were G
      banded with the aid of a modified technique elaborated in the Department of
      Clinical Genetics, Lund University Hospital (Sweden). The slides were incubated
      for 1-4 min at room temperature in 0.01 versene solution, containing 0.011% w/v
      trypsin (Difco), 0.4 mg/ml D-glucose, 0.17 mg/ml KCl, 1.7 mg/ml NaCl. Following a
      15 sec incubation in a solution containing 1 mg/ml D-glucose, 0.4 mg/ml KCl, 8
      mg/ml NaCl, G-banding was completed by staining the slides with 2% Giemsa (Merck)
      in pH 6.8 phosphate buffer for 4-5 min.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266580
TI  - [DNA replication in intact and X-ray-irradiated cells in the Cockayne syndrome].
AB  - Using DNA fiber autoradiography, an estimation was made of DNA replication in
      normal fibroblasts and in those derived from a patient with Cockayne syndrome.
      The rate of replication fork movement as well as the rate of DNA chain growth,
      dependent on the frequency of initiation sites in the adjacent clusters of
      replicons, did not differ in Cockayne syndrome cells, compared to cells of normal
      donors, either before or after exposure to ionizing radiation.

PMID- 8266581
TI  - [Autoradiographic and biochemical studies of protein synthesis in nucleated
      erythrocytes during the formation of their segregation apparatus].
AB  - It has been shown that during novocaine (4.6 x 10(-3) M) induced formation of the
      segregation apparatus (SA) the total protein synthesis decreases, the synthesis
      of certain proteins being characterized by a high rate turnover. In the intact
      erythrocytes, 1 x 10(-2) cycloheximide (CHM) inhibits the novocaine induced
      formation of segregation apparatus (SA) and protein synthesis by 90%. The
      combined action of novocaine and CHM on erythrocytes is accompanied by a decrease
      in CHM inhibiting effect on protein synthesis. This effect retains for 1.5 h
      during the action of both compounds. Some vacuoles of SA disposed cytochemically
      exposed acid phosphatase (AP), which enabled us to consider these as lysosomes.
      According to AP distribution in lysosomes, they can be classified into 3 groups.
      In group 1 AP is distributed along the membrane of vacuoles, in group 2 it is
      associated with the material inside the lysosome, and in group 3 the enzyme is
      both distributed along the membrane and associated with the material enclosed
      within the segregation vacuole. Such a mode of AP distribution reflects
      presumably the functional heterogeneity of lysosomes.

PMID- 8266582
TI  - [The isolation of monoclonal antibodies to hepatoma-associated nonhistone
      chromosomal proteins from rat kidneys].
AB  - A monoclonal antibody (5D2) has been produced to a fraction of nonhistone
      proteins of kidney origin, associated with the rat hepatoma 27 and not obtained
      in normal liver. The 5D2 antibody was found to precipitate three proteins with
      molecular weights of 22-23 kDa. Indirect immunofluorescence studies on fixed
      hepatoma cell-preparations showed speckled nuclear staining patterns. In
      contrast, the 5D2 antibody was unreactive with intact hepatocytes.

PMID- 8266583
TI  - [Changes in the orientation of the smooth-muscle cells of the tunica media from
      major arteries under constant lengthwise stretching in situ].
AB  - It has been shown that changes in the orientation of arterial smooth muscle cells
      during a constant longitudinal stretching of the artery in vivo are not similar
      in different sections of the stretching zone. Cells in the proximal and distal
      sections keep their orientation but this orientation differs from that of smooth
      muscle cells in the control arteries. Cells in the central part of the stretching
      region lose their definite orientation to settle randomly.

PMID- 8266584
TI  - [The growth stimulation of a cell culture of dissociated rat embryonic spinal
      cord under the influence of the opioid peptide dalargin and the opioid receptor
      blocker naloxone].
AB  - Effect of synthetic analog of [Leu]-enkephalin dalargin and naloxone as a opioid
      blocker on fetal rat spinal cord cells was studied. It was found that the
      aggregation place during dalargin action had increased on average by 1.85
      compared to the control, during naloxone action had increased on average by 1.78
      compared to the control. The fact that brain cells reactions on opioid and on
      naloxone are the same and naloxone-peptide mixture is more active by 2.5 times
      compared to control suggests that these agents effect the cells with the help of
      receptors of different types, thus these agents are growth factors for nervous
      tissue, they increase survival and adhesion of the cells of CNS.

PMID- 8266585
TI  - Introduction: electron microscopy of soft tissue and bone tumors.

PMID- 8266586
TI  - Proliferative disorders of myofibroblasts.

PMID- 8266587
TI  - Fibrosarcoma: observations on the ultrastructure.
AB  - Ultrastructural observations on 60 fibrosarcomas are presented. Myofibroblastic
      differentiation was found in 33 tumors but usually in scattered cells. Diffuse
      aggregates of nonspecific intermediate filaments were present in a number of the
      tumors. Electron microscopy is useful to distinguish fibrosarcoma from other soft
      tissue sarcomas that it can resemble by routine light microscopy, and its value
      is enhanced when selected immunocytochemical procedures are also performed.

PMID- 8266588
TI  - Leiomyosarcoma versus myofibrosarcoma: observations and terminology.
AB  - Two spindle cell sarcomas, which showed similarities in light microscopic
      histology and immunostaining and were diagnosed as leiomyosarcomas by these
      criteria, were compared ultrastructurally to show the value of electron
      microscopy in subtyping these neoplasms. Both were subcutaneous, case 1 occurring
      in the nasolabial fold and case 2 in the upper calf. Both consisted of fascicles
      of spindle cells, and both stained positively for vimentin and alpha-smooth
      muscle actin; only case 2 stained additionally for desmin. Case 1 showed strong
      and case 2 weak or negative staining for fibronectin. By electron microscopy,
      case 1 contained prominent rough endoplasmic reticulum, peripheral fine filaments
      with focal densities, and fibronexus junctions. By contrast, case 2 was
      characterized by an external lamina and well-developed bundles of fine filaments
      with focal densities. Case 2 was considered a typical leiomyosarcoma, and case 1
      was interpreted as showing myofibroblastic differentiation. The nomenclature for
      these myofibroblastic tumors is discussed, and myofibrosarcoma and
      leiomyosarcoma, myofibroblastic variant are suggested as suitable terms.

PMID- 8266589
TI  - Leiomyosarcoma of the upper extremity.
AB  - A case of rapidly fatal, high-grade leiomyosarcoma of the upper extremity is
      described. The pleomorphic appearance of this sarcoma on light microscopy
      required the use of immunohistochemistry and electron microscopy to establish the
      morphologic diagnosis and to exclude a diagnosis of other high-grade sarcoma,
      such as malignant fibrous histiocytoma or pleomorphic rhabdomyosarcoma. The
      observed clinical behavior of this leiomyosarcoma of the upper extremity seemed
      unusually aggressive compared with the biologic behavior predicted by the
      independent prognostic indicators of location, tumor size, and depth of invasion.
      The observed clinical behavior did not seem unusual compared with the clinical
      behavior predicted by the use of a staging scheme for soft tissue sarcomas.

PMID- 8266590
TI  - Plexiform soft tissue tumor composed predominantly of perineurial fibroblasts
      (perineurioma).
AB  - A 15-year-old girl presented with a small, indolent mass near the knee joint.
      Light microscopy revealed a peculiar myxoid plexiform tumor composed of
      cytologically bland cells. Interpretation of the initial biopsy material was
      controversial. Subsequent immunohistochemical studies revealed tumor cells to be
      strongly reactive for epithelial membrane antigen (EMA) and negative for S-100
      protein. Ultrastructural studies revealed tumor cells with long, thin, bipolar
      cell processes and discontinuous basal laminae. They had no epithelial or
      histiocytoid features. Admixed among the tumor cells were Schwann cells, but they
      represented a rare and scattered component of the overall cell population. These
      features are most consistent with a so-called perineurioma and contrast with
      those of plexiform neurofibroma and traumatic neuroma (two lesions strongly
      positive for S-100 protein and showing a distinctive EMA immunoreactivity pattern
      with focal peripheral staining of neural bundles).

PMID- 8266591
TI  - Perineurial cell differentiation in benign tumors and tumorlike proliferation of
      peripheral nerves.
AB  - An unusual, benign, spindle cell peripheral nerve sheath tumor (PNST) is reported
      that on ultrastructural examination was composed only of perineurial cells. The
      neoplastic cells showed positive immunoreactivity for S-100 protein and negative
      immunoreactivity for epithelial membrane antigen; this is not the expected
      immunophenotype of a perineurioma. Continued examination of benign PNSTs using
      electron microscopy and immunohistochemistry has the potential to reveal
      additional variations in the cellular composition and immunophenotype of these
      soft tissue tumors. PNSTs such as the one described will renew the debate about
      the cytogenesis of the perineurial cell and its role in PNSTs.

PMID- 8266592
TI  - Importance of angulate bodies in the diagnosis of granular cell tumors
      (schwannomas).
AB  - Granular cell tumors (GCTs) were originally characterized ultrastructurally by
      the presence of many large lysosomes and angulate bodies (ABs). ABs appear to
      have been forgotten, and the diagnosis of GCT currently depends solely upon the
      presence of large lysosomes. Most investigators favor a Schwann cell origin for
      GCT. Recently, reports of granular tumors with large lysosomes but without ABs
      have suggested other cells of origin. If the ultrastructural criteria for the
      diagnosis of GCT were maintained as originally described, many of these granular
      tumors would not qualify as true GCTs. Two granular tumors that were at first
      considered GCTs are described. Based on the presence of large lysosomes and the
      presence or absence of ABs, one tumor was considered a true malignant GCT and the
      other a benign fibroblastic tumor.

PMID- 8266593
TI  - Crystal-deficient alveolar soft part sarcoma.
AB  - Classically, ultrastructural examination of alveolar soft part sarcoma reveals
      large, dramatic, rhomboid to needlelike crystals with a characteristic
      substructure. In this study of four cases of alveolar soft part sarcoma, only two
      exhibited large crystals, which were rare. All four cases, however, exhibited
      round, electron-dense granules, and in the two cases without large crystals these
      granules rarely exhibited elongation with the characteristic substructure of
      alveolar soft part sarcoma that permits definitive diagnosis. Two of these cases
      had been previously studied at other institutions, where crystals were not
      identified ultrastructurally and electron microscopy was considered
      noncontributory. Large crystals, then, may be rare or absent in alveolar soft
      part sarcoma. Careful search may be necessary to find granules with the
      characteristic periodic substructure.

PMID- 8266594
TI  - Epithelioid monophasic synovial sarcoma.
AB  - A 47-year-old man presented with a soft tissue mass of the distal right thigh
      near the knee. The tumor was highly vascular with epithelioid tumor cells growing
      in a peritheliomatous pattern, suggesting a soft tissue glomus tumor. Yet many
      tumor cells contained hemosiderin pigment and formed papillary structures
      suggestive of pigmented villonodular synovitis. Tumor cells were cytologically
      bland, and there was minimal mitotic activity. The tumor cells were strongly
      immunoreactive for cytokeratin, however, and contained true desmosomes, gland
      lumina, microvilli, tonofilaments, and well-developed basal lamina. These
      findings plus the absence perinuclear aggregates of intermediate filaments rule
      out malignant rhabdoid tumor and epithelioid sarcoma. Also, magnetic resonance
      imaging revealed no other lesions to suggest metastatic carcinoma. Thus this
      tumor appears to be a predominantly epithelioid form of monophasic synovial
      sarcoma. Recognition of this variant of synovial sarcoma is important for
      prognostication and therapeutic decision making because some studies indicate
      that this variant of synovial sarcoma follows a relatively benign clinical
      course.

PMID- 8266595
TI  - Peritoneal desmoplastic small round cell tumors with divergent differentiation: a
      review.
AB  - Peritoneal desmoplastic small round cell tumors with divergent differentiation
      are recently described highly aggressive neoplasms with characteristic clinical,
      morphologic, and immunohistochemical features. This review covers 38 cases that
      have been reported in the literature. The average age of patients is 18.4 years,
      and males are affected twice as frequently as females. Tumors generally present
      as multiple peritoneal nodules without obvious organ involvement. Histology shows
      islands of small cells set in dense desmoplastic stroma. Immunohistochemical
      stains are usually positive for cytokeratins, epithelial membrane antigen,
      desmin, and vimentin. Many cases also stain for neuron-specific enolase but
      rarely for other neuroepithelial markers. Ultrastructural appearances range from
      undifferentiated small cells to larger epithelial elements. Paranuclear
      aggregates of intermediate filaments are characteristic. Dense-core granules and
      other neuroendocrine features have been described in a minority of cases. Some
      tumors respond to chemotherapy, but most patients die within months to a few
      years. The histogenesis of these tumors is uncertain.

PMID- 8266596
TI  - Small intestinal stromal tumors with skeinoid fibers in neurofibromatosis: report
      of four cases with ultrastructural study of skeinoid fibers from paraffin blocks.
AB  - Small intestinal stromal tumors (SIST) with skeinoid fibers (SF) are reported in
      four patients with neurofibromatosis. SF appeared as intercellular eosinophilic
      globules that stained positively on periodic acid-Schiff stain and bluish on
      Masson trichrome stain, like those reported previously. Electron microscopic
      confirmation of SF was carried out on tissue retrieved from paraffin blocks,
      which revealed diagnostic ultrastructural features of SF. The association of SIST
      with SF and neurofibromatosis enhances the diagnostic value of SF as a marker of
      neurogenic spindle cell tumors. This study also underscores the importance of
      electron microscopy for differentiation of SF from pseudoskeinoid structures,
      which may mimic SF on light microscopic examination.

PMID- 8266597
TI  - Use of electron microscopy in the diagnosis of uncommon lung tumors.
AB  - We have demonstrated the value of electron microscopy in the study of ten
      uncommon lung tumors. Ultrastructural examination contributes toward the accurate
      classification of unusual lung tumors, and may clarify their histogenesis.

PMID- 8266598
TI  - Melanotic paraganglioid carcinoid tumor: a case report and review of the
      literature.
AB  - An unusual case of peripheral melanotic paraganglioid carcinoid tumor of the lung
      is described. By light microscopic, immunohistochemical, and electron microscopic
      examination, melanocytic, schwannian, and neuroepithelial lines of
      differentiation were evident. This case may represent another example of
      neoplastic multidirectional differentiation and highlights the close relationship
      among the genes represented in these three cell lines. In addition, these
      findings support the concept of a neoplastic origin for the sustentacular cells
      found in some bronchial carcinoid tumors.

PMID- 8266599
TI  - Role of electron microscopy in metastatic endometrial stromal tumors.
AB  - Endometrial stromal tumors may pose a problem in diagnosis when they appear as
      metastatic lesions without a known primary tumor. To determine the usefulness of
      electron microscopy in identifying them in these situations, optimally fixed low
      grade stromal sarcomas (five), normal endometrial specimens (six), and malignant
      mesodermal mixed tumors (four) were studied. The endometrial stromal sarcomas had
      a general resemblance to normal proliferative endometrial stroma, being composed
      of undifferentiated cells, fibroblasts, and myofibroblasts. One stromal tumor
      showed evidence of partial epithelial differentiation. One of the four malignant
      mesodermal mixed tumors had a fibrosarcomalike component, but there was
      insufficient resemblance to normal endometrial stroma to indicate a relationship
      between the two. Together with a review of the literature, this study indicates
      that electron microscopy is useful in the diagnosis of low-grade endometrial
      stromal tumors by demonstrating characteristic cellular findings as well as a
      lack of features specific for other round cell and spindle cell neoplasms.

PMID- 8266600
TI  - Ultrastructure of an endometrial stromal nodule with skeletal muscle.
AB  - The ultrastructural appearance of an endometrial stromal nodule with prominent
      smooth and skeletal muscle differentiation is described. This is the first
      reported case of endometrial stromal nodule with a heterologous skeletal muscle
      component and emphasizes the value of electron microscopy and its correlation
      with immunohistochemistry in the study of rare or complex lesions.

PMID- 8266601
TI  - An update on the electron microscopy of small cell carcinoma of the ovary with
      hypercalcemia.
AB  - Since the first description of small cell carcinoma of the ovary with
      hypercalcemia in 1982, similar tumors have been reported, and more than 150
      additional cases have been seen in consultation. This tumor is the most common
      form of undifferentiated carcinoma of the ovary in women younger than 40 years
      and has a poor prognosis. It is now recognized to have a large cell component in
      40% of cases, and large cells occasionally predominate. The tumors are also
      unaccompanied by hypercalcemia in about one third of the cases. Microscopically,
      the most common pattern is diffuse sheets of compact cells, but clusters, cords,
      and folliclelike structures are also usually present as well. Mitoses are
      numerous. Immunostaining is almost always positive for keratin, often for
      vimentin, and occasionally for epithelial membrane antigen. Electron microscopy
      (19 cases) has revealed oval, polygonal, and occasionally elongated cells that
      are poorly differentiated but usually contain a moderate to large amount of
      dilated rough endoplasmic reticulum as their most constant cytologic feature.
      Junctions, including desmosomes and in some cases tight junctions, mark the cells
      as epithelial. The histogenesis of small cell carcinoma of the ovary is still not
      known, but it is usually possible to distinguish it from other small cell tumors
      of the ovary. Neuroendocrine cells and germ cells have been suggested as possible
      lineages, but the clinical and morphologic evidence is against those
      interpretations.

PMID- 8266602
TI  - Role of electron microscopy in head and neck pathology in adults and children.
AB  - Diagnostic electron microscopic studies specific to the head and neck region are
      limited in both children and adults. Even information about the workload created
      by specimen acquisition from this region in the electron microscopy laboratory is
      lacking. To address these deficiencies, various specimens gathered from adults (N
      = 6607) and children (N = 1556), over a 5- and 10-year period, respectively, and
      blocked in plastic resin were surveyed. Head and neck samples accounted for 16.4%
      of these samples from adults and 13.5% from children, representing sizable
      contributions to workload from an anatomic region amounting to less than 10% of
      body mass. In adults, diagnostic problems posed by metastatic neoplasms account
      for a considerable proportion of the cases submitted for electron microscopy; in
      the pediatric age group, undifferentiated primary tumors of the head and neck
      region frequently require ultrastructural study. In both circumstances, spindle
      cell, look-alike, neuroendocrine, and small cell tumors can frequently be rapidly
      assessed and differentiated by ultrastructural details. Problem cases are
      inevitable given the complexity of this region and the number of different
      tissues and organs in close proximity. It is advantageous to anticipate the
      possibility of encountering difficult differential diagnostic problems by
      sampling lesions of the head and neck for glutaraldehyde fixation more
      frequently.

PMID- 8266603
TI  - Plasmacytoma of the thoracic spine with intracellular amyloid and massive
      extracellular amyloid deposition.
AB  - A 65-year-old woman presented with back pain and a lytic destructive lesion of T
      11. Fine-needle aspiration biopsy revealed a granulomatous reaction with unusual
      signet ring type cells and vacuolated histiocytes. Subsequent resection of the
      lesion revealed a fibrohistiocytic reaction with extensive amyloid deposition.
      Immunoperoxidase stains confirmed monotypic kappa light-chain staining.
      Ultrastructural examination of paraffin-embedded tissue confirmed extracellular
      amyloid deposition. A unique feature of this case was the finding of
      intracellular amyloid; the unusual signet ring cells were shown to be plasma
      cells with intracellular amyloid, and the vacuolated histiocytes also contained
      amyloid.

PMID- 8266604
TI  - Abdominal neuroendocrine neoplasm with misplaced exocytosis.
AB  - A 22-year-old man presented with epigastric fullness and tenderness. A 14-cm mass
      that was adherent to the sigmoid colon was removed surgically. The tumor
      exhibited ultrastructural evidence of neuroendocrine differentiation but defied
      precise classification. The tumor exhibited misplaced exocytosis, a finding not
      previously described in neuroendocrine tumors other than prolactin cell adenomas.

PMID- 8266605
TI  - Clear cell melanoma of the bladder.
AB  - Primary malignant melanoma of the urinary bladder is a rare tumor. A case in a 34
      year-old man who presented with gross hematuria is reported. Cystoscopic biopsy
      showed a mixed spindle cell and clear cell neoplasm with focal pigmentation. The
      tumor cells were immunoreactive for S-100 protein and HMB-45. The patient did not
      have a history of melanoma, and clinical and radiologic work-up did not reveal
      other lesions, so a partial cystectomy and pelvic lymphadenectomy were performed.
      The tumor formed an ulcerated mass that extended into the perivesicular fat.
      Microscopically, the tumor was composed predominantly of clear cells in sheets or
      small nests. A solitary metastatic focus was present in 1 of 25 pelvic lymph
      nodes. Ultrastructurally, the tumor cells were characterized by irregular nuclear
      contours, complex nucleoli, abundant cytoplasmic glycogen, and premelanosomes.

PMID- 8266606
TI  - Benign clear cell thyroid tumor with "balloon cell" change: evidence suggesting
      its pathogenesis.
AB  - A unique benign clear cell tumor of the thyroid is described. The lesion was
      composed of swollen thyroid acinar cells distended by large membrane-bound
      vesicles. This picture was identical to the "balloon cell" change seen in nevi
      and melanomas. Only balloon cells with many relatively normal-appearing
      mitochondria but few membranous organelles were noted in all blocks of this
      tissue. On fine-needle aspiration biopsy smears, oncocytes and transitional cells
      with oncocytic and clear cell features were also observed. On the basis of the
      light and electron microscopic findings, the described vesicles are probably
      degenerative as in nevi and melanomas and are associated with membranous
      organelles. The observation of oncocytic areas indicates the strength of fine
      needle aspiration biopsy as a sampling technique. There is no evidence that these
      vesicles are of mitochondrial origin as in some clear cell thyroid lesions. Clear
      cell lesions of the thyroid are a heterogeneous group and may be benign,
      malignant, or metastatic.

PMID- 8266607
TI  - High-sensitivity lens-coupled slow-scan CCD camera for transmission electron
      microscopy.
AB  - A lens-coupled slow-scan CCD camera has been built for transmission electron
      microscopy (TEM) applications. In this design, a leaded glass window, which is
      coated with a 20 microns layer of red P20 phosphor, is mounted on the bottom of
      the microscope. A lens assembly and mirror prism, located outside the microscope
      vacuum below the leaded glass, relays the image onto a back-thinned 1kx1k charge
      coupled device (CCD) detector. This CCD is electronically cooled to below -30
      degrees C during operation. It is found that X-ray irradiation, generally found
      to be annoying in fiber-optically coupled CCD cameras, is completely eliminated
      by this configuration. The collection efficiency of this system, although not as
      high as some of the fiber-optically coupled CCD cameras, is high enough to
      achieve single-electron sensitivity under a high-gain mode.

PMID- 8266608
TI  - Glucose metabolism in renal stone patients.
AB  - The calciuric response and the changes of plasma glucose and insulin produced by
      a 75-gram oral glucose tolerance test were determined in 27 male patients with
      idiopathic calcium renal stones (6 with dietary hypercalciuria, 5 with nondietary
      hypercalciuria and 16 with normocalciuria) and 22 healthy male subjects. The
      subjects were classified as obese (> or = 120% ideal weight) and nonobese. The
      incidence of an abnormal response to glucose loading was similar in the stone
      patients and the healthy subjects. In addition, the plasma glucose and insulin
      levels after oral glucose load did not differ between the stone patients and
      control subjects and were affected by the individual degree of obesity. Urinary
      calcium excretion increased significantly after glucose ingestion in both the
      stone patients and the control subjects. Urinary calcium excretion was greater in
      the stone patients than in the control subjects due to the presence of patients
      with nondietary hypercalciuria, and the increment in urinary calcium excretion in
      the dietary hypercalciuric and normocalciuric stone patients was
      indistinguishable from that in the control subjects. The degree of obesity did
      not affect the increment in urinary calcium excretion. These results suggest that
      overconsumption of refined carbohydrates such as sugar-sweetened soft drinks,
      soda and cakes may be a risk factor for stone formation, especially in the
      patients with nondietary hypercalciuria.

PMID- 8266609
TI  - A retrospective evaluation of 691 ureteroscopies: indications, procedures,
      success rate and complications.
AB  - In the period of 1983-1990, a total of 691 ureteroscopies were performed in 480
      patients. The main indications for ureteroscopy were stones, stenoses or making a
      diagnosis. In one third of the cases, pathology was suspected in the renal pelvis
      or at the ureteropelvic junction, in one third in the distal third of the ureter,
      and in the remaining cases, in either the upper or the middle part of the ureter.
      The most frequent ureteroscopic procedures were diagnostic examination or
      surveillance and procedures involving treatment of stones. In the 1st attempt,
      the ureteroscope was introduced to the suspected pathology in 79.9% of all cases,
      and the main objective was achieved in 76.6%. The success of stone manipulation
      has increased from 74% in the 1st to 92% in the last part of the period. More
      than half the procedures involving a ureteral stenosis were not completed
      satisfactorily. The location of suspected pathology did not influence the
      results. Complications occurred in 23% of the ureteroscopies, and the relative
      number of major complications decreased continuously. We conclude that
      ureteroscopy is appropriate at any location of pathology and that efforts must be
      made to minimize both major and minor complications.

PMID- 8266610
TI  - Sex-dependent urolithiasis in the portacaval shunt rat. 2. Hormones and stone
      formation.
AB  - Sex-dependent stone formation following portacaval shunt (PCS) was investigated
      in 82 male and 71 female Sprague-Dawley rats. 72.6% of male PCS rats and none of
      the female PCS rats developed urolithiasis, in 90.2%, potassium-hydrogen-urate
      stones formed. Hormonal analysis revealed significant alterations in steroid
      hormones and glucagon postoperatively. Male PCS rats showed a significant
      decrease in total and free testosterone and an increase in estradiol and glucagon
      levels. Female PCS rats showed a marked rise in testosterone and glucagon levels
      as well as a decrease in estradiol plasma levels. Male PCS rats had higher
      urinary and plasma uric acid concentrations compared to female PCS and sham
      operated rats. Loss of testosterone and rise of glucagon in males was correlated
      with urolithiasis in so far as stone-forming rats had higher concentrations than
      non-stone-forming PCS rats. Our findings suggest that hormonal alterations might
      contribute to sex-dependent stone formation in PCS rats.

PMID- 8266611
TI  - Urine laminin P1 assessment discriminates between invasive and noninvasive
      urothelial cell carcinoma of the bladder.
AB  - In a cross-section study the levels of urine laminin P1 expressed as a laminin
      P1:creatinine ratio were determined in 25 patients with superficial (noninvasive)
      transitional cell carcinoma (TCC) of the bladder, 12 patients with invasive TCC,
      15 patients with inflammatory bladder diseases and 50 healthy controls. The mean
      of laminin P1:creatinine ratios in invasive TCC patients (4.83 +/- 3.05 U/mol
      creatinine) significantly differed from those of superficial TCC (2.60 +/- 1.07
      U/mol creatinine), inflammatory bladder disorders (2.38 +/- 1.74 U/mol
      creatinine) and controls (2.47 +/- 0.86 U/mol creatinine) (p < 0.03). At the
      individual patient level 7 out of 12 patients with invasive TCC, but only 1 out
      of 25 patients with superficial TCC, showed laminin P1 urine levels above the
      normal range (0.75-4.18 U/mol creatinine), thus giving a 58% sensitivity and a
      96% specificity of laminin P1 urine assessment in the discrimination between
      noninvasive and invasive disease. Given a 20-24% prior chance of invasive disease
      at initial diagnosis detection of elevated urine laminin P1 in TCC patients
      raises the posttest chance of invasive disease to 87.5%.

PMID- 8266612
TI  - Difficult urethral reconstruction.
AB  - A new technique using the pedicled island flap of penile skin for total urethral
      reconstruction is described. The technique consists of using a long, modified
      flap of more than 15 cm in length and was utilized in 6 cases of total urethral
      stricture. Four cases resulted in an excellent outcome, while 2 had fistula with
      anastomotic stricture. The technique is useful in reconstruction of the total
      urethra, but the utmost care is needed in the dissection to preserve the
      viability of the pedicle.

PMID- 8266613
TI  - Correction of distal hypospadias: ventral adaption of the prepuce and meatal
      advancement.
AB  - In distal hypospadias without chordee, surgical correction has a purely cosmetic
      character. In contrast to standard techniques focusing on meatal position,
      parents often regard the redundant dorsal prepuce and its missing ventral fusion
      as the essential constituent of this malformation. The operative technique,
      presented in detail, emphasizes on foreskin reconstruction. The ventral adaption
      of the prepuce (VAP procedure) results in a penis with normal appearance.
      Complications presented reveal the importance of proper patient selection.

PMID- 8266614
TI  - Extended vein ligation: a new aspect of the surgical treatment of varicocele.
AB  - Conventional varicocelectomy is complicated by a postoperative recurrence rate of
      5-20% in patients with varicocele. On the other hand, the exact location and
      relationship of the internal, external and gubernacular veins, arteries and
      lymphatics within the inguinoscrotal portion of the spermatic cord have not been
      well described. The results of detailed intraoperative observations and surgical
      dissection of the spermatic cord and gubernaculum are presented in 32 patients
      with clinically palpable varicocele. Following the identification of all veins
      within and around the spermatic cord and gubernaculum, dilated veins originating
      from the testis and traversing the gubernaculum were observed in 31% of the
      patients. External spermatic veins were present in 70% of all spermatic cords
      evaluated. The majority of patients (> 65%) had more than 3 internal spermatic
      veins. An average of 3.1 lymphatics per spermatic cord was identified and
      preserved during dissection of the cord. A solitary testicular artery was
      observed in 55% of the patients treated. In 3 patients with recurrent varicocele,
      by using intraoperative venography, we tried to demonstrate the relationship
      between the gubernacular, external spermatic veins and the plexus pampiniformis.
      Our results indicate that by giving a precise attention to varicocele anatomy and
      performing an extended vein ligation, better results together with decreased
      recurrence rates may be obtained.

PMID- 8266615
TI  - Results obtained from microsurgical therapy of varicocele.
AB  - The microsurgical method of varicocelectomy was performed in 56 patients. In 25
      cases the procedure was done because of scrotal symptoms and in 31 cases as a
      treatment for infertility. Complete regression of varicosities was observed in
      all the cases including 2 recurrent ones. The conception rate was 56% in the
      infertility patients excluding azoospermic and severe oligozoospermic ones. This
      microsurgical method has a good success rate and is also quite satisfactory in
      terms of its pregnancy rate.

PMID- 8266616
TI  - Reproductive insufficiency in the male rat with adenine-induced chronic renal
      failure.
AB  - The effect of adenine-induced chronic renal failure on the male reproductive
      system was studied using male Wistar rats. On the 30th experimental day, serum
      creatinine and urea nitrogen were elevated in adenine-treated rats. Body weight
      ratio of the testes and serum levels of gonadotropins (luteinizing hormone and
      follicle-stimulating hormone) in adenine-treated rats were similar to those in
      the controls. Serum testosterone level was reduced in adenine-induced uremic
      rats, but serum concentrations of 17 alpha-hydroxyprogesterone and
      androstenedione were increased in the uremic group. These results suggest that
      adenine-induced chronic renal failure reduces testicular function by suppressing
      17 beta-hydroxysteroid oxidoreductase which converts androstenedione to
      testosterone.

PMID- 8266617
TI  - Anorchia associated with gonadotropin deficiency.
AB  - We report an anorchic patient with normal male phenotype and 46,XY karyotype.
      Plasma levels of gonadotropins and testosterone were abnormally low.
      Administration of human chorionic gonadotropin caused no increase in plasma
      testosterone, and injection of luteinizing hormone-releasing hormone resulted in
      a lack of plasma gonadotropin response. Sex-determining region Y was detected by
      DNA studies of peripheral white blood cells. Laparoscopy revealed absence of
      testis, Wolffian and Mullerian derivatives. We discuss the embryology and hormone
      condition in an anorchic patient.

PMID- 8266618
TI  - 1.5-cm renal mass followed for 2 years without radiographic change.
AB  - An incidentally discovered 1.5 cm renal mass was followed by serial CT scans for
      a period of 2 years. The mass showed no signs of growth or change during this
      period. The patient underwent radical nephrectomy with pathology positive for
      renal cell carcinoma. The evaluation of small renal masses is reviewed.

PMID- 8266619
TI  - Urolithiasis with blind-ending ureteral duplication and azotemia treated with
      shock wave therapy.
AB  - A case of bilateral urolithiasis and renal insufficiency with a blind-ending
      branch of the right bifid ureter is presented. The diagnosis was made by
      retrograde ureterogram which revealed a blind-ending branch originating in the
      middle third of the right ureter. Stones were treated with phased extracorporeal
      shock wave lithotripsy after preliminary bilateral JJ stenting. The renal
      parameters reverted to normal and the patient was stone-free.

PMID- 8266620
TI  - Adenocarcinoma of the urachus associated with stromal osseous metaplasia.
AB  - Urachal adenocarcinoma is a rare bladder tumor, occasionally associated with
      calcification. We report a case of urachal adenocarcinoma with remarkable stromal
      osseous metaplasia and review the literature on this rare condition. This is the
      first complete case report in English of this uncommon entity.

PMID- 8266621
TI  - Posthernioplasty urinary retention: a noninvasive work-up for prediction.
AB  - The prognostic value of various subjective and objective noninvasive urological
      parameters was evaluated for their possible role in the prediction of post
      hernioplasty urinary retention. In a prospective study, 35 patients aged 55-85
      years without previous micturition complaints or urological surgery were
      evaluated 1 day prior to inguinal hernioplasty. This included medical history for
      modified Madsen subjective scoring profile, physical examination and
      uroflowmetry. Bladder capacity, residual urine and prostatic volume were measured
      by ultrasound. All patients underwent a similar method of hernioplasty, were
      closely followed 48 h postoperatively and any voiding difficulties or urinary
      retention were noted. Urinary retention occurred in 12 patients. None of the
      remaining 23 patients had urination difficulties. Comparing these two groups, we
      concluded that patient age, bladder capacity and prostatic volume have no
      prognostic value for potential postoperative urinary obstruction. On the other
      hand, obtaining a good anamnesis of obstructive and irritative symptoms for
      scoring, measuring maximal flow rate on urinary flowmetry and estimating residual
      urine volume may predict patients who are potentially at high risk for
      posthernioplasty urinary retention.

PMID- 8266622
TI  - Trypanosoma congolense in the microvasculature of the pituitary gland of
      experimentally infected Boran cattle (Bos indicus).
AB  - The pituitary glands of seven Boran cattle (Bos indicus), five infected with a
      clone of Trypanosoma congolense IL 1180 (ILNat 3.1) transmitted by Glossina
      morsitans centralis and two uninfected controls, were examined by light and
      electron microscopy 43 (experiment 2) or 56 (experiment 1) days after fly
      challenge. The three cattle used in the first experiment included a 15-month-old
      female (No. 1), a 24-month-old female (No. 2), and a 21-month-old male (No. 3) as
      a control. In the second experiment, four cattle were used: two females (Nos. 4,
      5) and one male (No. 6), all between 15 and 24 months of age, and one female
      control (No. 7) of similar age. In all the infected animals, dilation of both the
      sinusoids and microvasculature was apparent, as was an increase in the thickness
      of the extracellular matrix between the pituitary lobules. Trypanosomes were
      found in the microvasculature of the adenohypophysis and neurohypophysis in all
      the infected animals. Focal degenerative changes were seen in the
      adenohypophyseal section of glands from the infected animals euthanatized 56 days
      post-infection. These degenerative structural changes were confined to the
      somatotrophic cells. The possible role that trypanosomes in the microvasculature
      may play in inducing pituitary damage and dysfunction is discussed.

PMID- 8266623
TI  - Clinical signs and lesions in gnotobiotic pigs inoculated with Shiga-like toxin I
      from Escherichia coli.
AB  - Gnotobiotic pigs were used as a model to study the contribution of Shiga-like
      toxin I to natural disease caused by enterohemorrhagic Escherichia coli in calves
      and human beings. Eleven 2- to 7-day-old gnotobiotic pigs of either sex, obtained
      by closed hysterotomy, were injected intramuscularly with graded doses of
      partially purified Shiga-like toxin I derived from a lysogenized Escherichia coli
      strain. Four other gnotobiotic pigs were injected with a mock toxin preparation
      obtained from a nonlysogenized culture of the same E. coli strain. All toxin
      injected pigs developed diarrhea, and three displayed signs of neurologic
      disease. Pigs either died or were euthanatized 2 to 4 days post-inoculation.
      Necrosis of muscle was grossly evident at the site of injection in all toxin
      inoculated pigs. Hemorrhage in the lumen of the small and large intestines and
      blood in the feces were also evident in two toxin-inoculated pigs.
      Microscopically, severe necrotizing myositis at the injection site, multifocal
      encephalomalacia, and mucosal infarcts and hemorrhage in the small and large
      intestines were seen. In small vessels at lesion sites, endothelial cells were
      frequently swollen or necrotic. Pigs inoculated with mock toxin did not develop
      diarrhea or exhibit signs of neurologic disease, and the only apparent lesion was
      mild microscopic myositis at the injection site in 1/4 pigs. The results of this
      study indicate that Shiga-like toxin I causes vascular damage and ischemic
      necrosis in the intestines and brains of gnotobiotic pigs. These lesions are
      similar to those seen in the intestines of calves and human beings with
      hemorrhagic colitis and in the brains of human beings with thrombotic
      thrombocytopenic purpura.

PMID- 8266624
TI  - Polycythaemia vera in a dog treated by repeated phlebotomies.
AB  - Polycythaemia vera (PV) was diagnosed in a dog by demonstration of an increased
      red cell mass in association with normal arterial oxygen saturation and the
      absence of conditions known to be associated with secondary polycythaemia. The
      dog was treated exclusively by repeated phlebotomies and replacement of the
      removed volume by colloid and crystalloid solutions. It survived for one year and
      was generally free of signs.

PMID- 8266625
TI  - Elimination of aminoglycoside antibiotics in milk following intramammary
      administration.
AB  - The elimination in cow milk of aminoglycoside antibiotic residues (neomycin,
      dihydrostreptomycin, kanamycin and gentamicin) was studied after intramammary
      administration of eight drug formulations marketed in France. Quantitative
      residue analysis was performed by a cylinder plate method. The sensitivity was
      0.15 microgram/ml for neomycin, dihydrostreptomycin, kanamycin and 0.025
      microgram/ml for gentamicin. The mean elimination periods ranged between 4 and 13
      milkings. Several ways of assessing withdrawal times are discussed.

PMID- 8266626
TI  - Clinical and radiographic manifestations of canine malignant histiocytosis.
AB  - The results of clinical and radiographic examinations of 15 dogs with confirmed
      malignant histiocytosis (MH) were reviewed. The most common clinical signs were
      anorexia (14 dogs), weight loss (13 dogs), lethargy (13 dogs), anaemia (11 dogs),
      and dyspnoea and/or coughing (8 dogs). Radiographs revealed abnormalities in all
      dogs, either intrathoracic (pulmonary nodules or consolidation [7 dogs],
      mediastinal masses [10 dogs], and incidentally pleural effusion [3 dogs]) or
      abdominal (hepatomegaly [6 dogs] and splenomegaly [2 dogs]), or both. MH occurs
      relatively frequently in Bernese Mountain dogs. Both clinical and radiographic
      signs are non-specific, but when they are present in a middle-aged Bernese
      Mountain dog, MH should be included in the differential diagnosis.

PMID- 8266627
TI  - Chicken anaemia virus influences the pathogenesis of Marek's disease in
      experimental infections, depending on the dose of Marek's disease virus.
AB  - Eight groups of 1-day-old chickens were inoculated with 0, 250, 5000, or 100,000
      white blood cells of chickens infected with Marek's disease virus strain K (MDV
      WBC). Four of these groups were additionally infected with 10(5) TCID50 chicken
      anaemia virus (CAV). At day 14 after inoculation, chickens infected with CAV had
      reduced haematocrit levels, reduced body weights, and depletion of the thymic
      cortex and bone marrow. Semi-quantitative immunohistochemical examination of
      nerves and visceral organs was performed at day 28 by immunoperoxidase staining
      in which a monoclonal antibody specific for leucocytes was used. CAV
      significantly enhanced the number of lymphoproliferative lesions induced by 5000
      MDV-WBC. In contrast, CAV significantly reduced the number of lymphoproliferative
      lesions induced by 100,000 MDV-WBC. Comparable results were found at day 61 after
      macroscopic examination of nerves and visceral organs. These findings show that
      the pathogenesis of MD in experimental infections appears to be enhanced or
      inhibited by CAV, depending on the dose of MDV.

PMID- 8266628
TI  - Inactivation of chicken anaemia virus in chickens by heating and fermentation.
AB  - The transmission of pathogenic microorganisms such as viruses by the use of
      animal products in animal feed constitutes a potential risk to the health of
      livestock. To reduce the risk, it is necessary to understand the survival of
      viruses during the processing of animal products to feed-stuffs. Since chicken
      anaemia virus (CAV) is very resistant to inactivation, we used it as a model for
      the inactivation of pathogenic viruses during treatment of animal products. It is
      concluded that fermentation of CAV viraemic tissue did not affect the
      inactivation of CAV, however, heating at a core temperature of 95 degrees C for
      30 min or 100 degrees C for 10 min is sufficient to inactivate CAV. Compared with
      the conditions for inactivation reported in the literature for other pathogenic
      viruses, our treatment is more stringent. CAV viraemic chickens are thus suitable
      as a model to test the heat inactivation of pathogenic viruses.

PMID- 8266629
TI  - Optic nerve response and retinal structure in rainbow trout of different sizes.
AB  - This study presents evidence of ultraviolet (UV) sensitive, ON center ganglion
      cells in the fish retina. We determined the spectral sensitivity of ON and OFF
      responses from the optic nerve mass potential in small (18.0 - 28.5 g) and large
      (59.5-835 g) rainbow trout, with special reference to UV sensitivity. Under a
      mid+long-wavelength adapting background, the ON response of small fish revealed
      the presence of a UV cone mechanism (lambda max 390 nm) which was absent in large
      specimens. Under similar background conditions, the OFF response of both small
      and large fish showed one sensitivity peak, dominated by inputs from an M-cone
      mechanism. An almost complete absence of the accessory corner cones from the
      retinal mosaic was correlated with the loss of UV sensitivity.

PMID- 8266630
TI  - Acetylcholinesterase and choline acetyltransferase localization patterns do
      correspond in cat and rat retinas.
AB  - Is acetylcholinesterase (AChE) a reliable marker for cholinergic activity in the
      cat and rat retinas? To evaluate this question, radial sections, labeled for
      AChE, have been compared to sections labeled for choline acetyltransferase
      (ChAT). Within the inner plexiform layer (IPL) of each species, two lightly
      stained AChE bands are revealed which correspond to the depths of ChAT
      immunoreactivity. Although retinal AChE is not limited exclusively to sites where
      ChAT is present, AChE and ChAT activity do occur in the same IPL sublaminae. Used
      with proper caution, AChE is a reliable secondary indicator of cholinergic
      activity.

PMID- 8266631
TI  - Aquatic vision and the modulation transfer properties of unlighted and diffusely
      lighted natural waters.
AB  - The modulation transfer function (MTF) of well-mixed unlighted and diffusely
      lighted samples of clear natural waters for path lengths up to 4 m was measured.
      The measuring conditions simulated the situation for horizontal aquatic vision.
      In unlighted water, the MTF decreased relatively slowly with increasing path
      length and spatial frequency up to 150 c/deg. We interpret this as the result of
      low-angle forward scattering of light from the target. For diffusely lighted
      water, the MTF fell much more rapidly with path length, but was nearly
      independent of spatial frequency. Here, scattering of ambient light into the
      light path contributes an additional veiling glare or path radiance, which is
      independent of spatial frequency but degrades the MTF strongly with increasing
      path length. These scattering processes are independent of wavelength in the
      visible spectrum. The modulation transfer properties of these waters do not
      preclude high aquatic visual acuity. However, the useful range of high acuity
      vision in diffusely lighted water is much less than for unlighted water. This
      places special requirements upon the design of high-acuity aquatic eyes.

PMID- 8266632
TI  - Spatio-temporal frequency separability in area 18 neurons of the cat.
AB  - Spatial frequency tuning curves were obtained at a series of temporal frequencies
      and/or velocities from neurons of Areas 17 and 18 of the cat, in order to assess
      the interaction between these spatial and temporal parameters. In the great
      majority of instances, for neurons in both Areas 17 and 18, we found the optimal
      spatial frequency invariant with the temporal frequency or velocity at which a
      neuron was tested. Thus in this respect, responses of neurons in Area 18, like
      those of Area 17, are separable in their dependence on spatial and temporal
      frequency.

PMID- 8266633
TI  - Photopigments and color vision in the nocturnal monkey, Aotus.
AB  - The owl monkey (Aotus trivirgatus) is the only nocturnal monkey. The
      photopigments of Aotus and the relationship between these photopigments and
      visual discrimination were examined through (1) an analysis of the flicker
      photometric electroretinogram (ERG), (2) psychophysical tests of visual
      sensitivity and color vision, and (3) a search for the presence of the
      photopigment gene necessary for the production of a short-wavelength sensitive
      (SWS) photopigment. Both electrophysiological and behavioral measurements
      indicate that in addition to a rod photopigment the retina of this primate
      contains only one other photopigment type--a cone pigment having a spectral peak
      ca 543 nm. Earlier results that suggested these monkeys can make crude color
      discriminations are interpreted as probably resulting from the joint exploitation
      of signals from rods and cones. Although Aotus has no functional SWS
      photopigment, hybridization analysis shows that Aotus has a pigment gene that is
      highly homologous to the human SWS photopigment gene.

PMID- 8266634
TI  - Discriminating the direction of second-order motion at short stimulus durations.
AB  - We measured the ability of human observers to discriminate the direction of
      motion of different spatial patterns presented for durations ranging from 0.021
      to 0.67 sec. The patterns were: (1) a vertical grating (spatial frequency 0.93
      c/deg at 5% contrast); (2) a "beat" pattern made by adding vertical gratings of
      6.3 and 5.4 c/deg both at 5% contrast moving in opposite directions (this pattern
      appears as a horizontally moving, 0.93 c/deg "beat"; i.e. spatial variation in
      the contrast of a stationary vertical grating of 5.8 c/deg); and (3) a "plaid"
      pattern made by adding gratings of 5.9 c/deg orientated +/- 81 deg from vertical
      (this pattern can also be expressed as a horizontally moving 1.9 c/deg beat in a
      horizontal grating of 5.8 c/deg). The direction of motion of the grating and the
      plaid pattern were discriminable at all durations tested. The direction of motion
      of the beat could only be discriminated at durations above approx. 200 msec. We
      suggest that this is a consequence of the fact that the moving beat is only
      visible to second-order mechanisms, and that second-order mechanisms for the
      analysis of motion operate more slowly than first-order mechanisms.

PMID- 8266635
TI  - Suppression of contrast sensitivity during eyelid blinks.
AB  - Each blink of the eyelids is associated with a concurrent suppression of vision
      that lasts as long as 200 msec. Saccadic eye movements are also associated with a
      concurrent suppression of vision. Previous studies suggested that blink and
      saccadic suppression may be the result of a single mechanism. Volkmann, Riggs,
      White and Moore [(1978) Vision Research, 18, 1193-1199] demonstrated that
      saccadic suppression is most evident for low spatial frequency stimuli. However,
      the effect of stimulus spatial frequency on blink suppression has not been
      evaluated. If blink suppression and saccadic suppression result from a single
      mechanism, then blink suppression should also exhibit its greatest effect at low
      spatial frequencies. The purpose of this study was to determine the effect of
      stimulus spatial frequency on blink suppression. The stimulus was a sine-wave
      grating presented at different times after the blink. Psychometric functions were
      produced from the data for each post-blink, stimulus onset time and a Weibull
      function was fit to the data to determine threshold. The magnitude and duration
      of blink induced contrast sensitivity suppression was found to depend on the
      spatial frequency of the stimulus employed (similar to saccadic suppression).
      This is further evidence that a single mechanism may produce both blink induced
      visual suppression and saccadic suppression.

PMID- 8266636
TI  - Different parameters control motion perception above and below a critical
      density.
AB  - The maximum displacement for the detection of apparent motion (Dmax) is measured
      using stimuli made up of Gabor function micro-patterns randomly distributed
      across the stimulus field. Previous studies using high densities of micro
      patterns have demonstrated Dmax to be dependent on the spatial frequency content
      of the stimulus and not the size of the stimulus elements. Here we report that
      Dmax increases suddenly when the number of micro-patterns in the visual field is
      reduced beyond some critical point. The number of micro-patterns at which the
      transition in Dmax occurs is found to be inversely proportional to the width of
      the micro-patterns along the axis of motion. Beyond this transition, for low
      density stimuli, Dmax is found to be dependent on both the number and size of
      micro-patterns in the stimulus field. These results are suggestive of the
      operation of different motion mechanisms under conditions of low vs high micro
      pattern density.

PMID- 8266637
TI  - Processing of linear elements in stereopsis: effects of positional and
      orientational distinctiveness.
AB  - The stereoscopic processing of small linear elements is probed through the
      comparative analysis of stereograms containing needles or crosses, differing in
      the local spatial arrangement and orientation of the elements, and the presence
      or absence of slant. Depending upon the details of the textural design, depth
      analysis may proceed faster with crosses than with needles, or the reverse. It
      proceeds faster with vertical than with horizontal needles, except in the case of
      unslanted regularly-spaced needles. On the whole the data suggest that the
      elements to be matched in a stereogram are first processed along a common
      pathway, in which positional regularity has a detrimental effect. In the presence
      of small linear elements, orientation-tuned neurons would be recruited and their
      participation would lead either to an inhibition effect when the elements are all
      similarly oriented, or to a facilitation effect when there is sufficient
      orientational diversity among the elements. Here, slant plays an indirect role,
      by widening the orientation spectrum in otherwise regularly oriented textures.
      Positional irregularity is useful to suppress false matches, while orientational
      diversity helps to stabilize the perceived surfaces.

PMID- 8266638
TI  - Ultraviolet-induced lenticular fluorescence: intraocular straylight affecting
      visual function.
AB  - Ultraviolet radiation (UVR) excitation of fluorophores within the crystalline
      lens results in intraocular straylight. These fluorescent emissions are known to
      increase with age. The visual effect of this increase in fluorescent straylight
      has not previously been published. In this study, the visual deficit associated
      with UV-induced lenticular fluorescence was measured for 61 normal subjects
      between the ages of 21 and 80 yr of age using the Regan visual acuity charts at
      varying levels of contrast. UVR was shown to decrease low contrast acuity and
      this loss increased linearly with age.

PMID- 8266639
TI  - Chromatic discrimination with variation in chromaticity and luminance: data and
      theory.
AB  - Boynton and Kambe developed a model of chromatic discrimination in which
      thresholds are mediated by two independent mechanisms: the short-wavelength
      sensitive (S-) cones (S-cone axis), and the middle-wavelength sensitive (M-) and
      long-wavelength sensitive (L-) cones (M/L-cone axis). In this study, we used a
      Maxwellian view optical system to investigate fundamental properties of the model
      as a function of chromaticity and luminance. We confirmed that discriminations
      along the S-cone axis were dependent on S-cone excitation level. However, changes
      in chromaticity and changes in mean luminance were not described by a single
      threshold-vs-radiance (TVR) template. We developed a model to account for the
      different effects of changing S-cone excitation by varying mean chromaticity and
      by varying mean luminance. M/L-cone discriminations showed a minimum at the L
      cone excitation to white, indicating strong opponency. The thresholds increased
      with luminance approaching a Weber region and showing parallel functions for
      differing chromaticities. These data are fit by a model allowing retinal gain
      controls and spectral opponency.

PMID- 8266640
TI  - Colorimetric purity discrimination: data and theory.
AB  - Colorimetric purity, measured as the first step from white toward the spectrum
      has a V-shaped function. Purity discrimination is best near 400 nm, least at 570
      nm and intermediate at mid-spectrum and long wavelengths. A much flatter function
      occurs when colorimetric purity is measured as the first step from the spectrum
      toward white. In this study, we applied the formulation of chromatic
      discrimination thresholds measured along the S-cone and M/L-cone axis to account
      for chromatic discrimination in the equiluminant plane. The modeling results show
      that the purity step from white has a 1.6 log unit calculated range, similar to
      the classical data. The purity step from the spectrum is much flatter. The
      predicted range is dependent on the individual variance in chromatic
      discrimination thresholds and the luminance level. We then used psychophysical
      procedures to test the model's predictions. The resulting purity discrimination
      functions were generally in agreement with the model. Our modeling indicates that
      discrepant data of colorimetric purity can be explained with the context of
      discrimination models.

PMID- 8266641
TI  - Infant eye movement asymmetries: stationary counterphase gratings elicit temporal
      to-nasal optokinetic nystagmus in two-month-old infants under monocular test
      conditions.
AB  - Tested monocularly, young infants classically show directional eye movement
      asymmetries, with optokinetic nystagmus (OKN) being more readily elicited by
      stimuli moving in the temporal-to-nasal (T-N) than in the nasal-to-temporal (N-T)
      direction. Since a counterphase grating is physically identical to two
      superimposed sinusoidal components moving in opposite directions, we wondered
      whether or not a counterphase grating would elicit T-N OKN in monocularly tested
      infants. Two-month-old infants were tested in a motion nulling paradigm. Under
      monocular test conditions, all infants showed T-N OKN in response to the
      counterphase grating. The results suggest that the young infant's visual system
      represents the counterphase grating in terms of its T-N and N-T components, and
      reduces the effective contrast of the N-T component prior to the generation of
      OKN. The results are discussed in relation to models of OKN asymmetries and the
      responses of direction-selective neurons to counterphase gratings.

PMID- 8266642
TI  - Complete interocular transfer of motion adaptation effects on motion coherence
      thresholds.
AB  - The binocularity of visual mechanisms in humans can be investigated by measuring
      the interocular transfer (IOT) of visual aftereffects. Cells in extrastriate
      visual areas of macaque, e.g. the middle temporal (MT) area, are uniformly
      binocular, whereas cells in striate area V1 vary in their degree of binocularity.
      Therefore, IOT of aftereffects mediated by extrastriate cortex should be nearly
      complete compared to the partial transfer (about 70%) found for aftereffects
      thought to be mediated by V1. If MT and other extrastriate areas play a
      significant role in motion perception, then IOT of motion adaptation aftereffects
      on the perception of moving stimuli should be nearly complete. After motion
      adaptation, the perception of global movement direction in partially coherent
      random dot kinematograms (RDKs) is temporarily impaired if the predominant
      direction of dots in the test stimulus matches that of the adaptation stimulus. I
      measured the IOT of this motion incoherence aftereffect in four observers. Post
      adaptation motion coherence thresholds were elevated equally for interocular and
      intraocular adaptation, indicating complete transfer of the aftereffect.
      Measurement of the classical motion aftereffect using the same stimuli and
      conditions showed partial or absent transfer. These data support the idea that
      extrastriate areas play a key role in motion perception and suggest that the
      motion incoherence aftereffect and the classical motion aftereffect may involve
      different mechanisms.

PMID- 8266643
TI  - A model for detection of spatial and temporal edges by a single X cell.
AB  - When an inhibitory visual stimulus is turned off, an increased rate of spike
      discharge is evoked which we term the "rebound response". This response exists as
      a part of different cell responses from the retina to the cortex. The rebound
      response, with its temporal dependence on stimulus parameters, has not been
      previously considered in models. Here we present such a model, and also show its
      dependence on stimulus duration and its turning off rate. The rebound response
      enables detection of temporal changes when a visual stimulus involves spatial
      changes. The temporal change detection is affected by the actual stimulus
      duration, which can also be seen as a cell memory operation.

PMID- 8266644
TI  - Studies on the dopamine-dependent modulation of amino acid-gated currents in cone
      horizontal cells of the perch (Perca fluviatilis).
AB  - The whole-cell patch-clamp technique was employed to record membrane currents
      from isolated horizontal cells in culture. Concentration-response relationships
      for currents induced by L-glutamate, kainate and quisqualate were measured.
      Preincubation with dopamine changed the parameters of the concentration-response
      curves in a particular way for each agonist. The maximum currents induced by
      glutamate increased by 50-100% and the EC50-values were slightly shifted to
      higher values. The increase of kainate-induced maximum currents after dopamine
      incubation did not exceed 30% but the EC50-values were clearly shifted to lower
      concentrations. Quisqualate-induced maximum currents were not enhanced by
      dopamine preincubation but the EC50-values were shifted to lower concentrations.
      The dopamine-dependent modulation was affected by removal of magnesium and
      preincubation with concanavalin A and aniracetam. The concentration-response
      relation and the time-course of the dopamine effect on glutamate-induced currents
      is described.

PMID- 8266645
TI  - Effects of hydroxylamine, digitonin and triton X-100 on photoreceptor
      (paraflagellar swelling) and photoreception of Euglena gracilis.
AB  - We present experiments that test the effects of agents commonly used in visual
      pigment investigations, namely hydroxylamine (NH2OH), digitonin and triton X-100,
      on the photoreceptor and photoreception of Euglena. Hydroxylamine reacts with
      free and opsin-bound retinal, in aqueous solution, to form stable oximes, whereas
      digitonin and triton X-100 are the most common extractants of rhodopsin. Since
      previous data indicate that the chromophore present in Euglena photoreceptor is
      retinal, we investigated the influence of these chemicals on this organelle. The
      effects of these agents were studied by means of phase contrast, fluorescence and
      transmission electron microscopy and photobehaviour experiments. Hydroxylamine
      inhibited the formation of the Euglena photoreceptor. Photoaccumulation
      experiments on hydroxylamine-treated cells showed that they are unable to
      perceive light. Digitonin solubilized the crystalline structure of the
      photoreceptor, whereas the triton effect was limited to the membranous structures
      of the cell, leaving the photoreceptor unimpaired.

PMID- 8266646
TI  - The effects of adaptation and masking on incremental thresholds for contrast.
AB  - Using a temporal two-alternative forced-choice procedure, we measured thresholds
      for detecting increments in contrast of a 2 c/deg vertical grating at a wide
      range of pedestal contrasts, (1) before and after adapting to a grating of the
      same orientation and spatial frequency, and (2) in the presence of superimposed
      masks that varied in either orientation or spatial frequency. The adapting
      grating and all masks were of fixed 40% contrast. The results show that prior
      adaptation and concurrent masking have qualitatively similar effects on
      incremental thresholds; both raise threshold at low pedestal contrasts and leave
      them unaltered at higher contrasts. But masks have greater effects than adaptors,
      the effect of an orthogonal mask, or one two octaves higher in spatial frequency,
      being about the same as a parallel adaptor of the same spatial frequency as the
      pedestal grating. The results are explained by a model of Ross and Speed [(1991)
      Proceedings of the Royal Society of London B, 246, 61-69] that assumes that masks
      and adaptors both reposition the transducer function of contrast sensitive
      mechanisms and that masks, but not adaptors, also stimulate the detecting
      mechanism.

PMID- 8266647
TI  - Visually guided attention is neutralized when informative cues are visible but
      unperceived.
AB  - The ability to voluntarily shift the focus of visual attention away from the
      focus of gaze was investigated in a novel paradigm designed to elaborate the
      stages of processing underlying this ability. A basic experimental method used to
      investigate guided visual attention involves measuring response times to targets
      presented at positions of which the observer has been informed by an orienting
      cue. Binocular rivalry was utilized to dissociate presentation of the orienting
      cue from visual awareness of that cue. The findings indicated that when an
      informative cue was presented to an eye during the dominance phase, thus reaching
      visual awareness, manual response times were significantly affected by cue
      validity. In contrast, when the same cue was presented to an eye during
      suppression, and thus was not seen by observers, response times were not
      influenced by cue validity. We conclude that to guide attention, neural signals
      registering informative visual cues must be processed at stages lying beyond the
      site of rivalry suppression. Implications for investigating the neural basis of
      visual attention are discussed.

PMID- 8266648
TI  - The effects of grating area and spatial frequency on contrast sensitivity as a
      function of light level.
AB  - Contrast sensitivity was measured as a function of retinal illuminance (I) for
      vertical cosine gratings of various circular areas (A) and spatial frequencies (f
      < or = 4 c/deg). Spatial frequency and grating diameter varied in inverse
      proportion to each other in order to keep the relative grating area (A x f2)
      constant at either 3.14, 12.6, 50.3, or 201 square cycles. At all grating areas
      and spatial frequencies contrast sensitivity in dim light first increased in
      proportion to the square root of retinal illuminance. Then the increase saturated
      and contrast sensitivity became independent of luminance level in bright light.
      For gratings with constant relative area contrast sensitivity functions were
      similar in shape and had the same maximum sensitivity but were shifted
      horizontally towards lower illuminances with decreasing spatial frequency.
      However, when replotted as a function of retinal illuminance divided by spatial
      frequency squared, contrast sensitivity functions fell on a common curve at all
      levels of relative retinal illuminance (I/f2).

PMID- 8266649
TI  - Orientation identification at different background levels: its precision and
      distortions.
AB  - Orientation identification was studied at high (1000 td) and low (1 td)
      background illuminations. The subject had to estimate in degrees the orientation
      of a line presented in one of 18 orientations, 10 deg apart. Unlike other spatial
      discriminations, the precision of orientation judgments was not significantly
      impaired at low background if a suprathreshold stimulation was used. However, our
      earlier data showed that the identification at threshold was deteriorated at low
      background level. Different mechanisms of threshold and suprathreshold
      identification were suggested. The mechanism of suprathreshold identification was
      thought to contribute to the stability of the orientation perception during
      adaptation. The deviations of the subjective estimates from real orientations
      were also studied. The bias of perceived orientation toward the vertical
      increased at low background. This bias remained the same in egocentric
      coordinates, when the subjects were in supine position.

PMID- 8266650
TI  - Accommodative microfluctuations and pupil diameter.
AB  - The nominally steady-state accommodation response exhibits temporal variations
      which can be characterized by two dominant regions of activity; a low frequency
      component (LFC < 0.6 Hz) and a high frequency component (1.0 < or = HFC < or =
      2.1 Hz). There is no consensus as to the relative contribution made by each of
      the frequency components of the microfluctuations to the control of steady-state
      accommodation. We investigate the effect of variations in artificial pupil
      diameter (0.5, 1, 2, 3, 4 and 5 mm pupils) on the microfluctuations of
      accommodation, while three young emmetropic subjects view, monocularly, a
      photopic high contrast Maltese cross target placed at a dioptric distance equal
      to their open-loop accommodation level. Average power spectra were calculated for
      five accommodation signals, each of 10 sec duration, collected for each viewing
      condition at a sampling rate of 102.4 Hz using a continuously recording infrared
      objective optometer. For artificial pupil diameters < or = 2 mm the power of the
      LFC was found to increase as a function of reducing pupil diameter, while for
      artificial pupil diameters > 2 mm the LFC was found to be relatively constant. No
      systematic change in the HFC with varying artificial pupil diameter was observed.
      Changes in the root-mean-square (r.m.s.) value of the fluctuations with varying
      pupil diameter were significant (one-way ANOVA, F = 8.507, P = 0.0001, d.f. = 89)
      and showed a similar form to the changes in the LFC.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8266651
TI  - Motion capture changes to induced motion at higher luminance contrasts, smaller
      eccentricities, and larger inducer sizes.
AB  - In the stimulus configuration for "motion capture" phenomenon, we varied
      luminance contrast of the center disk (target), eccentricity and stimulus size.
      The subjects had to judge the direction of perceived target motion. We found that
      motion capture changed to induced motion (the direction of illusory motion was
      reversed) at smaller eccentricities and larger stimulus sizes. At intermediate
      eccentricities, motion capture changed to induced motion with increasing
      luminance contrast of the target. By using magnitude estimation, we also found
      that even a luminance-defined target was captured ("homochromatic motion
      capture") and that a moving target was captured by a stationary inducer
      ("position capture"). Both motion and position capture effects were commonly
      observed at lower luminance contrasts of the target, larger eccentricities and
      smaller sizes. From these results, we propose a model of center-surround
      antagonistic motion contrast detectors in motion processing.

PMID- 8266652
TI  - What induces capture in motion capture?
AB  - The phenomenon of "motion capture" has been demonstrated by presenting, one after
      the other, two identical Kanizsa squares spatially separated and superimposed on
      a regular matrix of dots. For appropriate temporal intervals, one illusory square
      is seen to jump from one location to the other and the dots in it appear to move
      with it even though they are physically stationary. The standard explanation of
      the effect is that motion signals from the subjective figure are spontaneously
      attributed to the static elements laying on it. We have found, however, that if
      alternative removal of right-angle sectors (required to obtain apparent motion of
      the illusory square) is not accompanied by alternative appearance and
      disappearance of a few dots, motion capture does not occur. This suggests that
      the basic mechanism underlying capture is not the motion of the subjective figure
      per se, but the spreading of motion signals arising from those texture elements
      that alternately go on and off between frames. On the other hand, subjective
      contours do play a role by confining the spreading of motion signals to the
      texture elements located on the figure.

PMID- 8266653
TI  - Functional segregation of color and motion perception examined in motion nulling.
AB  - We examine two hypotheses about the functional segregation of color and motion
      perception, using a motion nulling task. The most common interpretation of
      functional segregation, that motion perception depends only on one of the three
      dimensions of color, is rejected. We propose and test an alternative formulation
      of functional segregation: that motion perception depends on a univariate motion
      signal driven by all three color dimensions, and that the motion signal is
      determined by the product of the stimulus contrast and a term that depends only
      on the relative cone excitations. Two predictions of this model are confirmed.
      First, motion nulling is transitive: when two stimuli null a third they also null
      another. Second, motion nulling is homogeneous: if two stimuli null one another,
      they continue to null one another when their contrasts are scaled equally. We
      describe how to apply our formulation of functional segregation to other
      behavioral and physiological measurements.

PMID- 8266654
TI  - Fading time of retinally-stabilized images as a function of background luminance
      and target width.
AB  - Fading time of a retinally-stabilized difference-of-Gaussian (DOG) stimulus
      depends on the background luminance, contrast and spatial frequency content of
      the stimulus. A model of the visual system including a nonlinear multiplicative,
      non-local and fast process followed by a linear subtractive, local and slower
      process accounts for these effects. Analysis of the fading time data allows us to
      estimate the spatiotemporal characteristics of the proposed adaptation processes.
      The model is consistent with recent models of normal light adaptation from the
      probe-flash paradigm.

PMID- 8266656
TI  - Directional discrimination of motion in depth based on changing target vergence.
AB  - Difference limens for the apparent direction of motion in depth were measured in
      eight observers. Two points of light were presented dichoptically in an otherwise
      dark field. Their lateral motion (changing target-vergence stimulus) mimicked the
      oscillation of an object in depth along different paths. All seven paths of 100
      cm length had a common distant position in the median plane 150 cm from the
      observer. The directions of the paths were equidistant; the second and sixth
      paths were directed toward the left and right eye of the observer, respectively.
      Discrimination of direction was best for motion along the median plane and
      deteriorated toward the periphery. There was no indication of local minima of the
      difference limen for motions toward the eyes as has been observed with changing
      disparity stimuli.

PMID- 8266655
TI  - Serine/alanine amino acid polymorphism of the L and M cone pigments: effects on
      Rayleigh matches among deuteranopes, protanopes and color normal observers.
AB  - In a first experiment, groups of deuteranopes and protanopes were characterized
      psychophysically by the slopes of regression lines fitted to yellow intensity
      settings from their Rayleigh matches. In a second experiment, color normal male
      subjects were characterized by their 2 and 8 deg Rayleigh match points. All
      subjects had been previously characterized genetically by the presence of the
      amino acid serine or alanine at position 180 on their L cone or L/M hybrid
      opsins. Dichromats and color normal subjects with serine had greater sensitivity
      to the red primary than did those with alanine. Calculations based on
      psychophysical results suggest that the substitution of serine by alanine in the
      L cone opsin or L/M hybrid opsin produces a shift in lambda max of the expressed
      pigment toward shorter wavelengths by an amount varying between 2.6 and 4.3 nm,
      with the shifts in lambda max for the dichromats being larger than those for the
      color normal subjects.

PMID- 8266657
TI  - Perceived location of two-dimensional patterns.
AB  - The study attempted to test the possibility that the center of gravity of two
      dimensional patterns is the cue used by a human observer for their localization.
      Four experiments were carried out. The first, using a matching procedure,
      required the localization of the center of irregular dot patterns, contour and
      filled polygons which varied in size and orientation. In the other three
      experiments the subjects had to point to briefly exposed dot patterns in which
      overall shape (convex and concave in Expts 2 and 3) and dot density (Expt 4) were
      manipulated. The performance of these direct localization tasks was found to be
      as accurate as the performance in previous studies of indirect localization or
      regular patterns. The results consistently supported the claim that information
      about position of the center of gravity is used for the localization of visual
      objects.

PMID- 8266658
TI  - [The role of ultrasonic activation of the thyroid in the development of stress
      changes in cardiac contractile function].
AB  - Ultrasonic activation of the thyroid is characterized by a rise in T3
      concentrations in the serum, acceleration of the rat myocardial contractility
      under isometric loading. Preliminary activation of the thyroid function restrains
      stress-related changes in thyroid hormone production and cardiac contractility,
      prevents reduction of iodized thyroglobulins in thyroid colloid under
      immobilization.

PMID- 8266659
TI  - [A differential approach to applying the terrain cure to adolescents with
      arterial hypertension].
AB  - The "severity index" obtained by specially devised algorithm and the type of
      central circulation served as the basis for adjustment of terrain exercise
      regimens in the treatment of hypertensive adolescents. The distance of the walk
      and the route topography were chosen differentially according to cardiac
      performance of each patient reflected in the above severity index of the disease.

PMID- 8266660
TI  - [The effect of a UHF electrical field used bitemporally on the clinical status of
      patients with ischemic heart disease and atherosclerotic lesions of the coronary
      arteries (II--III degrees of stenosis)].

PMID- 8266661
TI  - [The effect of transcardiac galvanization on the course of the physical
      rehabilitation of patients with an acute myocardial infarct based on the data
      from a measured loading test].
AB  - Transcardiac galvanization effect was assessed in 76 patients with primary
      noncomplicated macrofocal anterior myocardial infarction admitted to hospital
      within initial 6 hours of the disease. As shown by the evidence obtained at
      bicycle ergometry, tetrapolar rheography and clinical examination, transcardiac
      galvanization within 3 days of the infarction enhances hospital physical
      rehabilitation course, increases exercise tolerance by the disease month 6,
      promotes an increase in myocardial maximal oxygen consumption, increases coronary
      reserve and improves cardiac contractility.

PMID- 8266663
TI  - [The efficacy of speleotherapy in salt mines in children with bronchial asthma
      based on the data from immediate and late observations].
AB  - Speleotherapy was conducted in 216 children with bronchial asthma treated in
      conditions of salt mines situated near the town of Nakhichevan. The assessment of
      clinical, immunological and functional parameters showed that the best results
      had been achieved in atopic asthma running a light or moderate course.
      Speleotherapy courses noticeably diminished broncho-obstructive syndrome,
      improved pulmonary ventilation. The improvement proved stable in the majority of
      the patients. It is recommended to include speleotherapy in salt mines into
      combined rehabilitation treatment of pediatric asthmatics.

PMID- 8266662
TI  - [The use of magnetics and laser therapy in treating obliterating vascular
      diseases of the extremities].
AB  - The paper presents the results of treatment received by 60 patients suffering
      from lower limb vascular obliteration stage IIA-III. The treatment involved
      combined use of magnetic field and laser irradiation. Peripheral circulation and
      central hemodynamics were evaluated rheographically and using ultrasound Doppler
      sphygmomanometry. Combined application of the above two modalities produced a
      greater effect on central hemodynamics compared to them introduced alone.

PMID- 8266664
TI  - [The use of low-intensity millimeter waves in gastric and duodenal peptic ulcer].

PMID- 8266665
TI  - [The effect of radon therapy on the bacteriological and immunological indices of
      patients with intestinal dysbacteriosis].
AB  - Bacteriological and immunological indices were examined in patients with normal
      and dysbiotic intestinal microflora. Radon therapy demonstrated phasic pattern of
      its influence: negative changes in intestinal microflora immediately after the
      treatment course and normalization of intestinal microbiocenosis in the long-term
      period. The above trend was associated with positive responses in previously
      affected immune system.

PMID- 8266666
TI  - [The cerebral hemodynamics in patients with humeroscapular periarthritis under
      the influence of decimeter waves and deresinated naphthalan].
AB  - 110 patients with scapulohumeral periarthritis of vertebrogenic origin were
      exposed to decimetric waves or received salt-free naphthalan. There were also
      patients who got combined treatment with decimetric waves and salt-free
      naphthalan. REG recorded positive shifts in cerebral hemodynamics due to these
      factors utilization.

PMID- 8266667
TI  - [Changes in intracellular regeneration and the indices of endocrine function and
      cardiac microcirculation in exposure to decimeter waves].
AB  - An electron-microscopic study of rabbit heart with experimental myocardial
      infarction revealed that extracardiac exposure to decimetric waves (DW) activated
      intracellular regeneration in the myocardium. This was associated with enhanced
      circulation and endocrine activity in the heart. Most pronounced regeneration was
      registered in adrenal exposure, the effect of the parietal exposure being
      somewhat less.

PMID- 8266668
TI  - [Changes in the clinical electromyographic indices of patients with the
      hyperkinetic form of infantile cerebral palsy and their dynamics during combined
      sanatorium-health resort treatment including transcerebral exposure to an
      ultrahigh-frequency electrical field].
AB  - Clinical electromyographic studies were made to evaluate the efficacy of
      transcerebral exposure to UHF electric field which has been used as an adjuvant
      to therapeutic exercise, massage, climate treatment in 33 patients with
      hyperkinetic infantile cerebral paralysis (ICP). The effect on the motor
      disorders reached 70.8%. Specific features of statokinetic function in
      hyperkinetic ICP children recorded electromyographically dictate combined use of
      various modalities (therapeutic exercises, preformed physical factors, games,
      reflex therapy, etc.) to improve therapeutic actions on vestibular apparatus.

PMID- 8266669
TI  - [Lipid peroxidation in osteoarthrosis patients during sanatorium-health resort
      treatment].
AB  - It is suggested that a rise in plasma level of LPO products may be involved in
      osteoarthrosis pathogenesis. A direct correlation exists between elevated levels
      of diene conjugates, compensatory activity of antioxidant system and
      osteoarthritis form, history and season of the year. The highest LPO activity was
      observed in multiple articular lesions versus mono-osteoarthrosis. Compensatory
      potential of antioxidant system exhausted with the disease duration and is
      minimal in spring. The disease responded best to sulfurated hydrogen baths
      combined with laser treatment of the affected joints.

PMID- 8266670
TI  - [The stimulation of ureteral motor activity by ultrasound in ureterolithiasis].
AB  - The paper presents methodological and therapeutic aspects of the experiment in
      which rabbit ureters were stimulated with ultrasound. Rectal exposure to the
      ultrasound made impulses from the ureteral smooth muscle significantly more
      frequent in 100% of the animals, applications of the ultrasound to the skin
      produced the same results in 70% of the test animals. The authors also achieved
      clinical effects in 63.6% and 86.7% of patients with ureteroliths or their
      fragments, respectively, in the low third of the ureter following combined
      treatment which involved oral mineral water, sodium chloride baths and
      ultrasound. The effect was evident after a single treatment course.

PMID- 8266671
TI  - [The therapeutic efficacy of the Russian bath].
AB  - Some mechanisms of steam inhalation effects in patients with nonspecific
      pulmonary diseases have been investigated. This type of aerosol therapy proved
      highly effective due to its broncholytic, antimicrobial and pulmonary hemodynamic
      stabilizing actions.

PMID- 8266672
TI  - [Changes in the energy apparatus of the ischemic myocardium and in the thyroid
      hormones under the action of the helium-neon laser with obzidan].

PMID- 8266673
TI  - [The prevention of reproductive disorders in women after surgical interventions
      on the fallopian tubes].

PMID- 8266674
TI  - [The system of the health conditioning and sociomedical rehabilitation of
      patients with infectious and noninfectious diseases modelled on the prevention
      and rehabilitation centers of Caucasian Mineral Waters].

PMID- 8266675
TI  - [Testing of the SKENAR-032 apparatus (a neuroadaptive electrostimulator)].

PMID- 8266676
TI  - [Bacterial contamination of the apparatus for hygrothermal inhalations, of the
      mineral water aerosol and of the compressed air used for inhalations].

PMID- 8266678
TI  - [The regulation of medical terminology in the area of health resort medicine and
      physiotherapy].

PMID- 8266677
TI  - [The therapeutic effects of ultrasound and their use in cardiology].

PMID- 8266679
TI  - [The history of the organization of sanatorium-health resort treatment in the
      Urals in 1919-1920].

PMID- 8266680
TI  - [The evaluation of the efficacy of adaptation to intermittent normobaric hypoxia
      as a method for treating hypertension].
AB  - Clinical and functional condition was examined for 75 patients with essential
      hypertension stage I and II who had developed adaptation to normobaric cyclic
      fractionated hypoxia. The latter was produced by gas hypoxic mixture (10% oxygen,
      90% nitrogen) in its inhalation. A pronounced positive effect of such treatment
      modality was registered in 86.7% of the patients and persisted for 6 months and
      more in 84.3%. A normal correlation was achieved of cardiac ejection to
      peripheral vascular resistance, this reducing arterial pressure. An optimal
      hemodynamic response arose to the hypoxic effects which also improved
      psychoemotional status of the patients.

PMID- 8266681
TI  - The changing pattern of early breast cancer and its primary management at CAMC.
AB  - To gauge the impact of screening mammography and the results of clinical trials
      on the pattern of primary surgical care of early breast cancer, tumor registry
      data from the Charleston Area Medical Center for 1980-81 was compared to tumor
      registry data at the hospital for 1990-91. Over the course of 10 years, there was
      a significant increase in the proportion of patients with T1 tumors (52% vs. 66%,
      p = .004), a significant increase of cases diagnosed by mammography alone (6% vs.
      34%, p < .001), a significant decrease in the proportion of patients with
      positive axillary nodes (41% vs. 28%, p = .016), and a significant increase in
      the proportion of patients undergoing breast-sparing procedures (4% vs. 16%, p =
      .003). However, the percentage of breast-sparing operations at CAMC from 1990-91
      was lower than the number reported in the National Cancer Data Base of 1988 (16%
      vs. 29%). A future study to assess reasons for patient selection of mastectomy or
      local excision is being planned.

PMID- 8266682
TI  - Management of deep vein thrombosis of the lower extremity in pregnancy.
AB  - Deep vein thrombosis (DVT) of the lower extremity during pregnancy is infrequent,
      but its complication, pulmonary embolism, remains an important cause of maternal
      mortality. To evaluate the best method of caring for patients with DVT, we
      reviewed the records of patients at the Charleston Area Medical Center from 1987
      1992 who were treated for this condition. Twelve patients were treated with
      conventional continuous intravenous heparin for 7 days-10 days followed by
      subcutaneous heparin until 6 weeks-8 weeks after delivery. The other group
      consisted of nine patients who were treated with lower dose subcutaneous heparin
      for 7 days-10 days and maintained as the first group, but a Greenfield filter was
      inserted for patients with iliofemoral DVT. The patients who received low-dose
      heparin and Greenfield filters tended to do better than those who received high
      dose conventional heparin treatment. However, since there were so few patients
      evaluated, further verification is needed.

PMID- 8266683
TI  - Breast cancer--a medical disease?
AB  - The treatment of breast cancer has changed significantly over the last 20 years.
      It is now believed that breast cancer usually spreads early and that removal of
      neither lymph nodes nor the breast prolongs survival, although these procedures
      do improve local control of the disease. Involvement of lymph nodes is
      prognostically important as a reflection of the body's defenses against spreading
      cancer cells. Systemic adjuvant therapy with tamoxifen improves survival in
      estrogen receptor (ER)-positive women and chemotherapy does so in ER-positive or
      negative women. This article gives an overview of the evolution in the treatment
      of breast cancer over the past 20 years, and describes the Breast Cancer
      Prevention Trial (BCPT) and several trials of adjuvant therapy which are now
      being conducted by the National Surgical Adjuvant Breast Project (NSABP).

PMID- 8266684
TI  - "The plan" means Americans must make tough choices.

PMID- 8266685
TI  - Health care disaster.

PMID- 8266686
TI  - [Renal trauma].
AB  - An analysis is presented of 70 patients treated for renal trauma in the I
      Department of Urology in Katowice in the years 1974-1989. Renal damage was
      evaluated according to a three-grade scoring system. Conservative treatment was
      given to 43 patients (61.4%), including 14 patients with I degree trauma, 12 with
      II degrees, and 17 with III degrees trauma. Nephrectomy was performed in 17
      cases, and 10 sparing operations were carried out--one combined with splenectomy.

PMID- 8266687
TI  - [Cranioplasty of bone defects with "Codubix" plates].
AB  - Codubix plates made of polypropylene-polyester fabric were used for
      reconstructive cranioplasty of cranial vault defects after trauma. This method
      protected well the brain against secondary trauma with a good cosmetic result of
      the operation. By eliminating the necessity of use of patient's own bones the
      duration of operation was shortened, the patient avoided postoperative pain, and
      the possibility of postoperative complications was reduced. During a two-year
      period of follow-up no complications were observed.

PMID- 8266688
TI  - [Polycythemia].
AB  - On the basis of own material, the authors discuss the epidemiology, clinical
      picture, and results of treatment of newborns with polycythaemia. An analysis
      shows that the blood hyperviscosity syndrome is an underestimated cause of many
      pathological signs in newborns.

PMID- 8266689
TI  - [Topical treatment of oral bleeding in children with clotting disturbances].
AB  - Owing to substitutive therapy an inhibition is possible of bleeding from oral
      mucosa as well as stomatological procedures in children with haemorrhagic
      diathesis. For elimination or limiting of substitutive therapy in 29 children
      with congenital haemorrhagic diathesis caused by plasma or platelet disorders,
      tissue glue was used. The preparation Tissucol, IMMUNO, was given during 37
      stomatological procedures in which 44 tooth were extracted, and for post
      traumatic bleeding from oral mucosa. Very good and good results were obtained in
      95% of the performed stomatological procedures. That makes possible a statement
      that Tissucol is effective in maintaining of local haemostasis in children with
      haemorrhagic diathesis. This method is safer and less expensive than blood
      derived preparations used for substitutive therapy, and is especially valuable in
      the treatment of children with haemophilia type A with antibodies against factor
      VIII.

PMID- 8266690
TI  - [Concentration of selected trace elements in serum and erythrocytes of children
      with chronic renal failure and am attempt at deficiency correction with animal
      blood preparation].
AB  - The results are presented of studies in 32 children with chronic renal failure
      treated conservatively in whom the value was evaluated of serum Mg, Zn, and Se
      concentration, and erythrocyte Mg, and Zn concentration. Among the patients a
      group of 15 children was isolated whose diet was enriched with the animal blood
      preparation brown Livex containing among others the studied trace elements.
      Significant Zn and Mg deficiency was demonstrated in the serum and Mg deficiency
      in the erythrocytes of the ill children which were effectively corrected after
      three months of supplementation with the preparation Livex.

PMID- 8266691
TI  - [Level of magnesium in blood serum in children from the province of Rzesz'ow].
AB  - In 142 girls and 107 boys aged 5-15 years serum magnesium level was determined by
      the colorimetric method. Decreased values were found in 24 children including 7
      boys and 17 girls. In 21 of them neurotic reactions or concentration disturbances
      were observed.

PMID- 8266692
TI  - [Biological developmental parameters in newborns in Silesia born between the 30th
      and 42nd week of pregnancy].
AB  - On the basis of anthropometric data from 2985 newborns in Silesia, percentile
      grids were constructed of birth weight, height, head circumference, and chest
      circumference for boys, girls, and both sexes jointly. It was found that these
      parameters, especially in premature babies, were lower in comparison to those
      accepted for the whole country.

PMID- 8266693
TI  - [Histiocytosis X in children--course of the disease and treatment].
AB  - A clinical analysis was carried out of the course of the disseminated form of the
      disease in 20 children aged from one month to 8 years (mean age 11 months).
      Unfavourable prognostic significance was confirmed of such factors as: child's
      age at the time of falling ill lower than two years, number of the involved
      organs and their dysfunction, and lacking reaction to treatment during the first
      three months of the disease.

PMID- 8266694
TI  - [Urinary system irregularities as a background of acute and chronic nutritional
      disturbances in infants].
AB  - An analysis was carried out of 362 infants with urinary system infections (USI)
      hospitalized in the years 1987-91. Using USG and X-ray examinations abnormalities
      were found in 90 cases (24.9%), half of which were vesicoureteral refluxes. Of
      interest was the correlation of USI in the infants with such things as: weight
      deficiency (896 cases--26.5%), diarrhoea (130 cases--35.9%), malabsorption
      syndrome (20 cases--5.5%). Effective treatment of USI caused simultaneously a
      regression of gastrointestinal sings which indicated the aetiological and
      pathogenetic correlation between these two facts.

PMID- 8266695
TI  - [Ploidy as a prognostic factor in large bowel cancer].

PMID- 8266696
TI  - [Nalbuphine--properties and clinical use].
AB  - Nalbuphine--a new opioid drug with agonistic-antagonistic action is presented.
      The action of the drug is discussed in the light of present theory of opioid
      receptors. On the basis of literature reports the experiences are analyzed of the
      clinical use of nalbuphine.

PMID- 8266697
TI  - [Leukemic changes in the myocardium of a patient with acquired valvular heart
      disease].
AB  - A rare case is described of extensive myocardial infiltrations during myeloid
      leukaemia in a patient with coexistent valvular heart disease, and active
      inflammatory process in the endocardium. The coexistence of these diseases caused
      even greater diagnostic difficulties. This case shows also that differential
      white blood cell sound should not be disregarded in cardiovascular diseases.

PMID- 8266698
TI  - [A case of Wolman's disease in a two-month old boy].

PMID- 8266699
TI  - [Syndrome of hemorrhagic shock and encephalopathy in a newborn with generalized
      hemangiomatosis of the skin].
AB  - A case is described of a newborn with generalized haemangiomatosis of the with
      clinical symptoms and sings resembling the syndrome of haemorrhagic shock and
      encephalopathy. It seems that this syndrome, described for the first time by
      Levin et al. in 1983 is of special interest because of its sudden onset, dramatic
      course, and high mortality.

PMID- 8266700
TI  - [Netherton's syndrome in a 12-year old girl].
AB  - A case is presented of a 12-year-old girl with skin changes existing since birth
      which (in spite of the lack of changes in hair structure) were regarded as a
      coexistence of generalized ichthyosiform erythrodermia and atopic dermatitis, and
      which were diagnosed on the basis of literature data as Netherton's syndrome.
      Several weeks of treatment with non-steroid ointments, new generation
      antihistamines with the use of elimination diet gave an evident improvement and
      made possible her discharge in fairly good general condition, with suggested
      further treatment in the allergy outpatient clinic.

PMID- 8266701
TI  - [Complications after extracorporeal shock wave lithotripsy (ESWL) and methods of
      management of such cases].
AB  - The authors presented the complications which occurred in patients after
      extracorporeal shock wave lithotripsy (ESWL), and discussed the methods of
      management of such patients. It was found that the most common complications
      were: renal colic, fever, "calculus route", and, less frequently, subcapsular and
      perirenal haematomas. In most patients conservative treatment was adequate. Some
      of these patients required admission to hospital and proper specialized
      management.

PMID- 8266702
TI  - [Concentration of magnesium and lipids in blood serum in a group of young healthy
      medical students].
AB  - The concentration of magnesium and lipids was determined in the blood serum of
      100 healthy medical students (57 women and 43 men) aged 22.3 on the average.
      Decreased values of magnesium concentration below 0.8 mmol/l were found in 28% of
      the studied subjects. In 14% of the persons magnesium concentration was below the
      lower range of own laboratory normal values which were 0.66 for men, and 0.70
      mmol/l for women. Hypercholesterolaemia was found in 15% of the studied subjects.
      No relation was shown between magnesium concentration and the concentration of
      most blood lipids.

PMID- 8266703
TI  - [Changes of thyroid hormone levels in the perioperative period in patients with
      various types of goiter].
AB  - The thyroid hormone level was studied in the perioperative period in patients
      with various types of goitre. The clinical material comprised 85 patients treated
      surgically for nodular neutral goitre, nodular hyperactive goitre, Graves-Basedow
      disease, and cholecystolithiasis. The determination of total and free thyroid
      hormone blood serum levels was carried out in three periods of time, that is 4-5
      days before operation, immediately after operation, and on the fifth day after
      operation. The obtained results led us to reaching the following conclusions: 1.
      Achieving of clinical euthyroid state in patients with Graves-Basedow disease
      during preoperative preparation with thyrostatic drugs was connected with the
      decrease of total and free thyroid hormone levels below the lower range of normal
      values which persisted immediately after, and on the 4th-5th day after operation.
      2. During operation no significant increase was found of serum thyroid hormone
      levels. 3. On the 4th-5th day after operation, especially in patients with
      nodular neutral goitre and cholecystolithiasis a tendency was observed for a drop
      of triiodothyronine level, especially of its free fraction level.

PMID- 8266704
TI  - [Treatment of anemia in pregnant women with an animal blood preparation,
      "Livex"].
AB  - The animal blood preparation Livex obtained from the Agricultural Academy in
      Wroclaw was used for treatment of anaemia of pregnancy. During four weeks of
      treatment (3 x 7.0 g of Livex added to diet) a statistically significant increase
      was found of anaemia parameters such as haemoglobin level, value of haematocrit,
      red blood cell count, and mean corpuscular volume. Other parameters such as mean
      corpuscular haemoglobin mass, and mean corpuscular haemoglobin concentration were
      also increased but statistically insignificantly. Livex is an effective and safe
      preparation causing no side effects in view of the presence of certain trace
      elements in it, especially iron, copper, zinc, cobalt, and selenium. The use of
      this preparation in the treatment of anaemia of pregnancy is a natural and
      effective method of erythropoietic process stimulation.

PMID- 8266705
TI  - The health of women in paid employment: effects of quality of work role, social
      support and cynicism on psychological and physical well-being.
AB  - The possible benefits of the workplace experience for women were examined in
      terms of four determinants; rewards and concerns intrinsic to the job, rewards
      and concerns extrinsic to the job, social support and cynicism as a measure of
      attitude. Benefits were identified in terms of three psychological well-being
      measures: self-esteem, depression and quality of life and in terms of one
      physical well-being measure: symptomatology. Data were obtained from one hundred
      and twenty Canadian women in managerial or professional occupations and in
      clerical-type occupations. Analyses consisted of correlations and hierarchical
      multiple regression. Intrinsic factors were generally related to psychological
      well-being while extrinsic factors were more closely associated with physical
      health. Findings with regard to the beneficial effects of social support in the
      workplace were not specific, however a cynical attitude can influence the value
      of the work role, with effects being particularly marked in the clerical group.
      Because of its relationship with health, it is recommended that cynicism is
      included in future women's studies.

PMID- 8266706
TI  - Assessment of the impact of female circumcision on the gynecological,
      genitourinary and obstetrical health problems of women from Somalia: literature
      review and case series.
AB  - Approximately 80 million women worldwide have undergone surgery for circumcision.
      A variety of health risks resulting from the procedure have been reported in the
      literature including: bleeding, infection, shock, difficulties with menstruation
      and urination as well as painful intercourse. Prolonged labor and perinatal
      difficulties have also been noted. After an extensive literature review, a
      description of gynecological and obstetrical complications is provided. We had
      the opportunity to survey 12 Somali refugee women who were temporarily residing
      in a refugee center in Western New York about their personal experience with
      circumcision. We were interested in determining whether this convenient sample of
      women substantiated the clinical sequelae of circumcision reported in the
      literature. Structured interviews were conducted and included questions on
      sociodemographic, circumcision and health factors. Our findings, however limited,
      support the presence of heavy bleeding at the time of the surgery as a
      complication arising from circumcision.

PMID- 8266707
TI  - Childspacing intervals and abortion among blacks and whites: a brief report.
AB  - Although physical, psychological, and social problems for children born to women
      denied abortion have been identified, little attention has been paid to the role
      that close childspacing might play in contributing to those problems. Small
      childspacing intervals (less than two years) have been linked to numerous
      physical, psychological, and social problems for mother and child. Using
      secondary analysis, this study examines the characteristics of 596 mothers who
      sought abortions in 1987 by race and age. Nearly 25% of these mothers had at
      least one child under two years of age. Abortion patients with such young
      children were more likely to be Black and have low incomes than abortion patients
      with older children. More than half of the mothers studied had more than two
      children. The findings suggest that a substantial number of children born to
      women denied access to abortion would be closely spaced, with the resulting
      adverse health consequences falling more heavily on subpopulations of abortion
      patients already at higher risk for negative perinatal and neonatal outcomes.

PMID- 8266708
TI  - "Choice" as a double-edged sword: information, guilt and mother-blaming in a high
      tech age.
AB  - Women in the United States experience pregnancy in the context of more medical
      interventions than ever before. Procreative technologies can enhance both the
      range of choices for women and the possibility of greater social control of
      women's choices. Sometimes procreative technologies are a matter of routine, not
      choice. New developments in genomic research and prenatal diagnosis may lead to
      the routinization of further medical interventions in pregnancy. Women
      increasingly may lose the freedom to choose not to use prenatal tests or the
      information they provide. This article is drawn from a study of women's
      experiences of pregnancy. The women's stories and two examples of recent news
      reports demonstrate some of the pressures women face as they attempt to make
      choices about pregnancy and motherhood. The examples indicate that women face
      subtle and overt pressures on their "choices."

PMID- 8266709
TI  - Calling Jane: the life and death of a women's illegal abortion service.
AB  - In May, 1972, seven Chicago women were arrested and charged with performing
      illegal abortions. Over the course of the preceding five years, the members of
      Jane, as this illegal abortion collective was denoted, had arranged, assisted and
      performed nearly 15,000 illegal abortions. The very fact that Jane existed as
      long as it did and assisted as many women as it did, was evidence of the central
      role that abortion and other reproductive decisions play in women's daily lives.
      Jane began amid the political and social discontent of the late 1960s. Like the
      Chicago Women's Liberation Union, Jane was founded by women helping other women.
      This action was, in effect, a continuation of the centuries old women's health
      network. Records of the Chicago Women's Liberation Union, words and deeds of the
      city's feminists and interviews with members of Jane, permit a consideration of
      important medical, philosophical and historical issues that surround the
      turbulent issue of abortion. In this setting the boundaries between and
      definitions of lay and medical practitioners become indistinct, the differences
      between women-centered and physician-centered medical care become more obvious,
      and at the very least Jane provides evidence of a model system by which women a
      generation ago successfully confronted restrictive abortion practices.

PMID- 8266710
TI  - Aging and working capacity. Report of a WHO Study Group.

PMID- 8266712
TI  - Do no harm.

PMID- 8266711
TI  - Evaluation of certain food additives and contaminants. Forty-first report of the
      Joint FAO/WHO Expert Committee on Food Additives.

PMID- 8266713
TI  - The best of times, the worst of times.

PMID- 8266714
TI  - Metastatic breast cancer 39 years after primary treatment.
AB  - The appearance of metastatic disease decades after primary treatment for cancers
      occurs rarely with cancers of the breast, malignant melanoma, and cancers of the
      kidney. Certainty about the relationship of primary and metastatic cancers is
      often limited by the absence of tissues showing identical histology, omission of
      various procedures and tests ruling out a new primary cancer, and follow-up data
      with treatment which supports the case for late recurrence. We report here the
      unusual case of an 84-year-old woman initially treated with mastectomies for a
      benign breast condition at age 39 and invasive breast adenocarcinoma at age 44. A
      pleural effusion developed at age 83 which showed adenocarcinoma. Physical
      examination and an extensive evaluation were unrevealing. Hormonal treatment has
      sustained remission of disease for 1 year.

PMID- 8266715
TI  - Iron status in atrophic glossitis: a pilot study.
AB  - We studied the relationship between laboratory markers of iron status and
      atrophic glossitis diagnosed clinically and documented with photographs. Nine
      subjects with glossitis underwent determination of CBC, ferritin, iron, and iron
      binding capacity. Five of the subjects had laboratory evidence suggesting iron
      deficiency.

PMID- 8266716
TI  - Milwaukee's medical students rise to meet Milwaukee's need.

PMID- 8266717
TI  - Mammography use in Wisconsin: 1987-1992.

PMID- 8266718
TI  - Surface glycoprotein of influenza C virus: inactivation and restoration of the
      acetylesterase activity on nitrocellulose.
AB  - The influenza C glycoprotein HEF was analyzed for acetylesterase activity after
      SDS-polyacrylamide gel electrophoresis and transfer to nitrocellulose membranes.
      Using a histological esterase assay, the glycoprotein was detected as a colored
      band indicating that it is enzymatically active. The enzyme activity was not
      affected by low pH, but was abolished after denaturation by SDS as well as after
      breaking the disulfide bonds by reducing agents. Glycoprotein inactivated by SDS
      regained its enzyme activity if the ionic detergent was displaced by either
      bovine serum albumin or a nonionic detergent. The stability of the enzyme
      combined with the color assay provides a convenient tool to study the
      acetylesterase activity of the influenza C virus glycoprotein.

PMID- 8266719
TI  - The complete nucleotide sequence of two cold-adapted, temperature-sensitive
      attenuated mutant vaccine viruses (cp12 and cp45) derived from the JS strain of
      human parainfluenza virus type 3 (PIV3).
AB  - Two cold-passaged mutant vaccine viruses (cp12 and cp45) derived from the JS wild
      type (wt) strain of human parainfluenza virus type 3 (PIV3) have been sequenced.
      These mutant viruses display the cold-adapted (ca), temperature-sensitive (ts),
      and attenuation (att) phenotypes. Sequence data indicate that both cp12 and cp45
      sustained nucleotide substitutions during cold passage and subsequent cloning.
      Fifteen nucleotide changes were present in cp12 and 18 in cp45. Of these changes,
      some were present in the sequence of the prototype wt strain (Wash/47885/57) or
      were non-coding changes present in the open reading frames (ORFs). These were
      considered unlikely to be of significance in contributing to phenotypic
      differences between the mutants and the JS wt. There were nine remaining changes
      in cp12 and eight in cp45 that would most likely contribute to their phenotypes.
      For cp12, two were non-coding changes in regulatory regions, one in the 3' genome
      leader and one in the NP gene transcription start signal. The remaining seven
      changes resulted in amino acid substitutions in NP, F, HN, and L. For cp45, two
      mutations were in a non-coding regulatory region, the 3' genome leader. The
      remaining six changes resulted in amino acid substitutions in F, HN, and L. Only
      one amino acid substitution was conserved between cp12 and cp45 (a valine to
      alanine change at position 384 of the HN gene). These results should prove useful
      in the future in understanding the genetic basis of attenuation of the cold
      passaged PIV3 candidate vaccine viruses.

PMID- 8266720
TI  - Nucleotide sequence of a nucleoside triphosphate phosphohydrolase gene from
      African swine fever virus.
AB  - A putative nucleoside triphosphate phosphohydrolase (NTPase) gene of African
      swine fever virus was identified by using a degenerate oligonucleotide probe
      derived from the nucleoside triphosphate binding motif, which is highly conserved
      among viral and cellular NTPases. The probe hybridized with fragments SalI E and
      EcoRI Q, which is entirely contained in the former one. Sequencing of this region
      revealed an open reading frame, designated Q706L, coding for a protein of 706
      amino acids, with a calculated molecular weight of 80,283. The deduced amino acid
      sequence of this open reading frame has significant similarity with the putative
      helicase encoded by the killer plasmid pGKL2 of Kluyveromyces lactis as well as
      with the NTPase I of vaccinia virus and entomopoxvirus and a subunit of the early
      transcription factor of vaccinia and fowlpox virus. The protein encoded by this
      open reading frame contains the sequence features characteristic of helicases of
      the superfamily II. According to this, we propose the inclusion of the product of
      this ASF virus gene in this superfamily.

PMID- 8266721
TI  - Nucleotide sequence of XhoI O fragment of ectromelia virus DNA reveals
      significant differences from vaccinia virus.
AB  - The nucleotide sequence of the 3913 base pair XhoI O fragment located in an
      evolutionary variable region adjacent to the right end of the genome of
      ectromelia virus (EMV) was determined. The sequence contains two long open
      reading frames coding for putative proteins of 559 amino acid residues (p65) and
      344 amino acid residues (p39). Amino acid database searches showed that p39 is
      closely related to vaccinia virus (VV), strain WR, B22R gene product (C12L gene
      product of strain Copenhagen), which belongs to the family of serine protease
      inhibitors (serpins). Despite the overall high conservation, differences were
      observed in the sequences of p39, B22R, and C12L in the site known to interact
      with proteases in other serpins, suggesting that the serpins of EMV and two
      strains of VV may all inhibit proteases with different specificities. The gene
      coding for the ortholog of p65 is lacking in the Copenhagen strain of vaccinia
      virus; the WR strain contains a truncated variant of this gene (B21R) potentially
      coding for a small protein (p16) corresponding to the C-terminal region of p65.
      p65 is a new member of the family of poxvirus proteins including vaccinia virus
      proteins A55R, C2L and F3L, and a group of related proteins of leporipoxviruses,
      Shope fibroma and myxoma viruses (T6, T8, T9, M9). These proteins are homologous
      to the Drosophila protein Kelch involved in egg development. Both Kelch protein
      and the related poxvirus proteins contain two distinct domains. The N-terminal
      domain is related to the similarly located domains of transcription factors Ttk,
      Br-C (Drosophila), and KUP (human), and GCL protein involved in early development
      in Drosophila. The C-terminal domain consists of an array of four to five
      imperfect repeats and is related to human placental protein MIPP. Phylogenetic
      analysis of the family of poxvirus proteins showed that their genes have
      undergone a complex succession of duplications, and complete or partial
      deletions.

PMID- 8266722
TI  - Expression of the human foamy virus bel-1 transactivator in insect cells.
AB  - The human foamy virus (HFV) bel-1 transactivator protein was expressed in insect
      cells by a recombinant baculovirus. For the generation of the recombinant
      baculovirus, Acbel-1, the bel-1 gene of an HFV mutant was used, that bears
      truncations in the bel-1 overlapping bel-2 open reading frame. Acbel-1 infected
      Sf9 cells produced high amounts of recombinant protein of the same
      electrophoretic mobility (36 kD) as bel-1 expressed in mammalian cells. The
      baculovirus expressed bel-1 protein was readily identified by a polyclonal rabbit
      serum directed against bel-1 in immunoblot assay. As in mammalian cells, bel-1
      was predominantly localized to the nucleus of Acbel-1 infected insect cells. The
      baculovirus expressed bel-1 protein will be of use to determine the action of
      this novel viral transactivator more precisely.

PMID- 8266723
TI  - Nucleotide and deduced amino acid sequences of the M and S genome segments of two
      Puumala virus isolates from Russia.
AB  - Hemorrhagic fever with renal syndrome (HFRS) is caused by viruses in the
      Hantavirus genus, family Bunyaviridae. Three serologically distinct hantaviruses,
      Hantaan, Seoul and Puumala viruses, are known to cause HFRS. We report here, for
      the first time, gene sequences of two human Puumala virus isolates, P360 and K27,
      obtained in an HFRS endemic region of the former Soviet Union. We compared the
      nucleotide sequences and the derived amino acid sequences of their gene products
      to a Puumala virus isolate from rodents.

PMID- 8266724
TI  - Current awareness on yeast.

PMID- 8266725
TI  - A data-base of chromosome III of Saccharomyces cerevisiae.

PMID- 8266726
TI  - Maternal mortality--a continuing tragedy.

PMID- 8266727
TI  - Community nutrition survey in an urban settlement in Papua New Guinea.
AB  - Results of a small nutrition survey carried out in an urban settlement in Port
      Moresby are presented. Anthropometric, dietary and socioeconomic data were
      collected on 90 children under five years old and 78 adults. 30% of the children
      under five years old were below 80% weight for age. Of the 31% of adults found to
      be undernourished, the majority were females aged less than 30 years. With
      respect to dietary information, most families appear to eat a variety of foods
      though no attempt was made to measure quantity of foods consumed. Rice is the
      single most popular food, with 69% of adults having consumed it the previous day.
      Despite the high reliance on purchased foods, income appears to be low with the
      majority of people relying on money from relatives and the sale of home produce.
      The recommendations made for appropriate health and nutrition education may be
      applicable for other growing settlement populations in and around Port Moresby
      and other urban centres of Papua New Guinea.

PMID- 8266728
TI  - Deliberate self-harm by means of kerosene fire by women in Papua New Guinea.
AB  - This paper reports the results of an investigation into the psychosocial and
      sociodemographic factors relating to 10 females admitted to the Burns Unit of the
      Port Moresby General Hospital with a common diagnosis of deliberate self
      inflicted burns by kerosene fire. All 10 patients were admitted during the first
      six months of 1990 and all originated from Gulf Province. 6 of the 10 patients
      died despite intensive, standard surgical management. Discussion of the results
      centres around the possible causes of the sudden increase in the number of
      patients presenting with burns caused by self-inflicted kerosene fire.
      Recommendations are made for some preventive measures.

PMID- 8266729
TI  - Haemophilia A in the highlands: the investigation and management of two families
      in Tari.
AB  - A 12-year-old boy from Tari in the Southern Highlands of Papua New Guinea
      presented with prolonged bleeding from a minor injury to the lip. He had a
      history of profuse bleeding and joint swelling following minor trauma. He has two
      younger brothers with a similar history. It was demonstrated that they had a
      coagulation profile compatible with factor VIII deficiency and a family tree
      suggestive of haemophilia A. A further case was investigated some months later.
      Despite the neighbouring places of residence of the two families no familial
      connection could be established by involved discussions between family members.
      This was confirmed by reviewing the data held on the demographic surveillance
      system of the Tari Unit of the Papua New Guinea Institute of Medical Research.
      These families are considered against a background of the diagnosis and
      management of this condition in a rural part of Papua New Guinea. The long-term
      support of these patients and other similarly affected individuals presents
      difficult clinical and ethical problems for rural health services.

PMID- 8266730
TI  - How much do outpatients know about drugs prescribed to them? A pilot study.
AB  - In a two-week-long pilot study, 21 outpatients with acute illness prescribed and
      dispensed with medications were interviewed, using a standard questionnaire, to
      assess how informed they were of their drug regimens and the source of that
      information. Some trends highlighted by the study included: (i) patients had a
      good knowledge of how much medication to take and how often to take it; (ii)
      patients had less knowledge of the exact timing of the medication and the total
      duration of a course; (iii) patients had poor knowledge of the intended actions
      of the drugs and side-effects; (iv) drug dispensers, more than prescribers,
      provided the patients with most of the information; (v) written instruction
      labels on drug packages were the only aid to memory, and the information they
      contained was very limited; (vi) 67% of the patients were literate but ability to
      read was not related to knowledge of their drug regimens; (vii) patients were
      very poor at asking questions of their prescribers or dispensers. Further studies
      involving a larger and more varied population sample are warranted.

PMID- 8266731
TI  - Culture and psychiatry.
AB  - The painstaking and always tentative effort to discover the universal
      characteristics of the human species differs in motive and attitude according to
      the arrogant anxiety-abating need for each of us to impose our own cultural
      categories upon others. When stemming from Europe this is seen by some as a form
      of psychiatric imperialism, by others as the fallacy of universalism and the
      primary of culture. Evidence from Papua New Guinea and other groups elsewhere
      show quite clearly that the noetic domains of those groups with different
      languages are so organized that the notion of a universal consensual science
      cannot be sustained.

PMID- 8266732
TI  - The prevalence of toxoplasma antibodies in pregnant patients attending the Port
      Moresby General Hospital antenatal clinic: a seroepidemiological survey.
AB  - In a survey of 197 consecutive pregnant patients who were attending the Port
      Moresby General Hospital antenatal clinic for the first time in the index
      pregnancy, the prevalence of IgG antibodies to Toxoplasma gondii was 18%. Only
      one patient had IgM antibodies. Of the sociodemographic characteristics examined,
      only highlands origin of the patient had a significant association with the
      presence of IgG antibodies.

PMID- 8266733
TI  - Designing a government dental service for Papua New Guinea.
AB  - Dentistry deals with all the diseases and injuries of the mouth, teeth, jaws and
      surrounding face (for all age groups). Over the past 30 years government dental
      services in Papua New Guinea have been modelled on a New Zealand dental service
      directed primarily at children and adolescents for treating tooth decay. In
      designing a government dental service for the future, the two basic goals must be
      to retain the natural dentition for life for all Papua New Guineans and to
      eliminate oral cancer. The basic principles for such a dental service are to
      build on the specific realities of Papua New Guinea, encourage widespread
      community participation, base the dental services on the whole family rather than
      the child, make dentistry an integral part of the health services, and make
      dental care available at every level of health service. The seven major factors
      in the design are the foundational role of the dental doctor, with clear roles
      for other dental workers, a sound career structure, provision of continuing
      education, an effective supervisory structure and statistical reporting system,
      and a long-term financial commitment from the government for dental services.
      Over the next few years the priorities in implementing the design are to
      concentrate in selected model areas, emphasize the prevention of mouth cancer and
      tooth loss, and minimize the restoration of decayed teeth.

PMID- 8266734
TI  - Multiple sclerosis: report of a case in a Papua New Guinean.
AB  - Multiple sclerosis is rare in equatorial countries and has not been diagnosed in
      the indigenous population of Papua New Guinea. We describe the clinical features
      of a young Papua New Guinean with optic neuritis and a myelopathy which we
      believe to be due to multiple sclerosis.

PMID- 8266735
TI  - Autotransfusion in splenic rupture.
AB  - Different methods of autotransfusion have been employed by various people in
      various places for various reasons. In Papua New Guinea autotransfusion has been
      practised, but the methods used have not been described and illustrated. In this
      case presentation we illustrate a simple inexpensive and aseptic method that was
      used at the Tabubil Health Centre to autotransfuse a young local man who ruptured
      his enlarged spleen when he was involved in a motor vehicle accident in August
      1991. The advantages of this method are mentioned. Also mentioned are other
      expensive methods of autotransfusion used in developed countries, and some
      surgical procedures in which these methods have been used.

PMID- 8266736
TI  - Manic episode secondary to cryptococcal meningitis in a previously healthy adult.
AB  - A case of a manic episode secondary to cryptococcal meningitis is reported.
      Cryptococcal meningitis is the most common cause of chronic meningitis in adults
      in Papua New Guinea and may rarely present with features of functional psychosis.
      Laboratory investigations on the cerebrospinal fluid such as the India ink smear
      and fungal culture for the detection of the organism and the latex agglutination
      test to detect the cryptococcal antigen are invaluable aids for making the
      correct diagnosis.

PMID- 8266737
TI  - A therapeutic approach to hypertension.

PMID- 8266738
TI  - [Recent advances in neuropharmacology of the centrally acting antitussive drugs].
AB  - Although cough is a useful physiological mechanism serving to clear the
      respiratory passage of fereign material and excess secretions, there are many
      situations in which cough does not serve any useful purpose but may only annoy
      the patient or prevent rest and sleep. In such cases physician should use
      antitussive drugs. A number of opioid and nonopioid drugs are known to reduce
      coughs as a result of their central actions. However, the exact mechanisms
      responsible for these antitussive drugs are not entirely clear. In this article,
      the author reviewed the recent advances of the neuropharmacology of the centrally
      acting antitussive drugs. Furthermore, the possible role of opioid receptor types
      in the regulation of the cough reflex was also discussed.

PMID- 8266739
TI  - [A study on the pharmacological mechanism of the mood stabilizer--the changes of
      the rat brain concentrations of monoamines and their metabolites after the
      administration of Li, CBZ and VPA for 14 days].
AB  - The concentrations of monoamines and their metabolites (refer to Tables 1 and 2
      about each material) in the rat whole brain except for the olfactory bulb and the
      pituitary gland were measured after the administration of lithium (Li),
      carbamazepine (CBZ) and valproic acid (VPA) for 14 days. The plasma levels of
      three drugs were each 0.96 +/- 0.21 mEq/L (Li), 14.216 +/- 3.78 micrograms/ml
      (CBZ) and 53.341 +/- 31.76 micrograms/ml (VPA). The brain concentrations of
      monoamines and their metabolites are shown on Tables 1 and 2, and their change
      rates of the administrated groups to the intact group as control on Figs. 1 and
      2. Some changes were similar, i.e. tryptophan, 5-HT, 5-HIAA and L-DOPA seemed to
      increase, and normetanephrine and 3-MT seemed to decrease in common in three
      groups. On the contrary, tyrosine, 3-o-methyldopa, DOPAC and HVA increased
      significantly in only VPA group. It is an uncertain supposition that the common
      increases or decreases on this study may show the common mechanism among three
      mood stabilizers, but these changes are very interesting because many reports
      have mentioned the relation between mood disorder and monoamine
      neurotransmission. Especially, the common increases of tryptophan, 5-HT and 5
      HIAA and the common decreases of 3-MT and normetanephrine may suggest some
      relation to the pharmacological mechanism of the mood stabilizer.

PMID- 8266740
TI  - MK-801 and dopaminergic system in electrically-induced convulsions in mice.
AB  - In this study, the effects of MK-801 and selective dopaminergic agents on
      electrically-induced convulsions in mice were examined. MK-801 (0.004-0.1 mg/kg,
      ip) showed significant and dose-dependent anticonvulsive effects, and the
      anticonvulsive effects of MK-801 (0.02 mg/kg, ip) were not antagonized by
      dopamine selective antagonists, SCH-23390 (D1, 0.1 mg/kg, sc), sulpiride (D2, 100
      mg/kg, sc) and pimozide (D2, 0.5 mg/kg, sc). Apomorphine (0.02-0.5 mg/kg, sc), a
      D1/D2 agonist, showed proconvulsant effect on electrically-induced convulsions.
      Dopamine selective antagonists, SCH-23390 (0.02-0.5 mg/kg, sc), sulpiride (5-100
      mg/kg, sc) and pimozide (0.1-2.5 mg/kg, ip), also showed proconvulsant effect.
      However, these effects of dopamine agonist and antagonists were not dose
      dependent. These findings suggest that the dopaminergic system neither plays an
      inhibitory role, at least on electrically-induced convulsions in mice, nor
      contributes to the anticonvulsant effect of MK-801 in electrically-induced
      convulsions.

PMID- 8266741
TI  - Effects of long-term treatment of haloperidol on D2 dopamine receptors in various
      areas of rat brain.
AB  - Effects of long-term treatment of haloperidol on D2 dopamine receptors in various
      brain areas were examined. Haloperidol treatment was found to increase the number
      of binding sites of D2 dopamine receptors in striatum, olfactory tubercle,
      hypothalamus and anterior pituitary, while Bmax of D2 receptors in hippocampus
      was decreased by haloperidol treatment. Therefore it is suggested that D2
      dopamine receptors in hippocampus and other brain areas are regulated
      differently.

PMID- 8266742
TI  - Wave-function and the concept of a nano-mental element of representation.
AB  - Scientific endeavour has often tried to localize superior cerebral functions
      either in areas like the ones described by Broca as being those connected with
      language in the left hemisphere, or in the huge array of the hundred billion of
      interconnected neurons. But in this last case the coined description of the
      "grandmother" neuron, tends to show humorously that hopes have fallen short of
      their target. Along the same lines, the specific timing of electric neural
      activity is known to take place around a few milliseconds, which seems to be
      insufficient to account for the high potential speed necessary to sustain the
      very massive and complex process which is involved in mental activity. It is
      therefore necessary to go down to a much smaller scale to explain the
      considerable speed of usual mental processes. That is the reason why we have
      proposed the Nano-Mental Element of Representation (NMER) as a possible candidate
      for describing these specific nano-indexes of mind. At that level (10(-10) to 10(
      9) meter), these mental processes can be associated with, or take the
      probabilistic aspect of, a wave function. This concept enables us to bring down
      the problems of temporal scaling to the quantum level and, therefore, make the
      extremely fast behavioral or sensory answers accessible to our appropriate level
      of observation.

PMID- 8266743
TI  - Orgons and biolons in theoretical biology: phenomenological analysis and quantum
      analogies.
AB  - In this paper we define two types of formal biological entities corresponding to
      biological levels of organization, the biolons and the orgons, the properties of
      which are phenomenologically analyzed and discussed. We examine then, in a rather
      speculative manner, how some characteristics of these entities may suggest
      analogies between properties of biological systems and some special features of
      quantum systems. These analogies are principally related to the specific roles
      played by these entities (relatively to matter-energy, for orgons, and to
      information, for biolons) in a biological system. They are funded on the formal
      equivalence between the temporal variations associated to the development of the
      orgons and the biolons, respectively, and the statistical distribution over the
      available energy levels of the two main types of quantum entities, the fermions
      and the bosons (the former being associated to the constitution of matter and the
      latter to the effects of interactions). This formal comparison leads us to put
      into correspondences the developmental duration in biological systems with the
      energetic structuration in quantum ones and the related characteristic times of
      the former with the temperature of the latter. We discuss briefly these
      correspondences.

PMID- 8266744
TI  - A modeling study of solute reabsorption along rat proximal tubule.
AB  - We present a model of steady state solute and water reabsorption along the rat
      proximal tubule. Major co- and counter-transport systems in the apical and
      basolateral cell membranes are described using kinetic descriptions based on data
      from the flows and solute concentrations along the length of the proximal tubule
      as a function of filtration rate and peritubular solute concentrations. We show
      that for many aspects of proximal tubule transport physiology this kinetics-based
      model is an adequate representation of the mammalian proximal tubule.

PMID- 8266745
TI  - Using computer algebra to determine rate constants in biochemistry.
AB  - In earlier work we have described how computer algebra may be used to derive
      composite rate laws for complete systems of equations, using the mathematical
      technique of Grobner Bases (Bennett, Davenport and Sauro, 1988). Such composite
      rate laws may then be fitted to experimental data to yield estimates of kinetic
      parameters. Recently we have been investigating the practical application of this
      methodology to the estimation of kinetic parameters for the closed two enzyme
      system of aspartate aminotransferase (AAT) and malate dehydrogenase (MDH) (Fisher
      1990a; Fisher 1990b; Bennett and Fisher, 1990): aspartate + alpha-ketoglutamate <
      -> glutamate + oxaloacetate; oxaloacetate + NADH <--> malate + NAD. In this paper
      we present a fuller (although not yet complete) analysis of the system. We show
      how symbolic estimates of the error behaviour of the parameters can be made, and
      used to identify those which are of kinetic significance. Finally we consider how
      metabolic control analysis can be applied directly to such a system.

PMID- 8266746
TI  - On the role of enzyme kinetic parameters in determining the effectiveness with
      which channelling can decrease the size of a metabolite pool.
AB  - Recently, it has been argued that the phenomenon of direct transfer of
      intermediate metabolites between adjacent enzymes, also known as metabolic
      channelling, would not decrease the concentration of those intermediates in the
      'bulk' solution. However, this conclusion has been drawn by extrapolation from
      the results of simulations with a rather restricted set of parameters. We show
      that, for a number of kinetic cases, the existence of metabolic channelling can
      decrease the size of the soluble pool of intermediates. When the enzyme(s)
      'downstream' of the channel have a catalytic capacity that is large relative to
      the enzymes 'upstream' of the channel, the decrease of concentration can be
      substantial (3 orders of magnitude).

PMID- 8266747
TI  - Control involving metabolism and gene expression: the square-matrix method for
      modular decomposition.
AB  - Control of DNA supercoiling by the free-energy of hydrolysis of ATP that involves
      gene expression is analyzed in terms of three levels of unconnected metabolic
      pathways. These are synthesis and breakdown of topoisomerase mRNAs, synthesis and
      breakdown of topoisomerase proteins and supercoiling and relaxation of DNA. The
      so-called square-matrix method previously developed for the control of metabolic
      pathways, is extended to deal with this hierarchical control system. It turns out
      that also in this case, the matrix of control coefficients is equal to the
      inverse of the so-called elasticity matrix, which contains all relevant
      elasticity coefficients as well as information about the structure and
      connectedness of the pathways involved. For a simpler case of a hierarchy of two
      systems, we demonstrate that the explicit matrix inversion method may be replaced
      by an implicit in which the regulatory effects that run through the other level
      are described by an additional elasticity coefficient which may then be treated
      as if local.

PMID- 8266748
TI  - The regulatory strength: how to be precise about regulation and homeostasis.
AB  - The concepts of regulation and homeostasis are of frequent use but lack a single
      universally accepted definition. Here we propose a definition of the regulatory
      strength and homeostatic strength, which allow to assess the importance of a
      regulatory pathway in a quantitative fashion.

PMID- 8266749
TI  - Organization of the Echinococcus multilocularis cyst: analytical study of
      histological sections by means of a neural network.

PMID- 8266750
TI  - The treatment of stab wounds in about 1600. The death of the three Henry's of
      France.
AB  - On the 10th July 1559, Henry II died of posttraumatic meningo-encephalitis due to
      a perforating trauma through his left eye. His third son, the last Valois king,
      Henry III succumbed on 5th of August 1589, four days after having been daggered
      in the abdomen. The sister's husband of the latter, king Henry IV, the first
      Bourbon king was deadly wounded by Ravaillac's knife in the left hemithorax on
      the 14th may 1610. If we dwell on the thought of how these 3 unfortunate French
      kings died, we can ask the question if round the year 1600 they could have a
      chance of survival if all the possible therapy methods existing at that time had
      been applied.

PMID- 8266751
TI  - Assessment of the damages by orbital blow-out fractures.
AB  - Recent developments of medical imaging such as CT scanning with three dimensional
      reconstruction (3D-CT) and magnetic resonance imaging (MRI), have had a profound
      impact on the diagnosis of maxillo-facial trauma, including orbital blow-out
      fractures. The authors discuss the pathology of orbital blow-out fractures, the
      current views concerning the etiopathogenesis and nowadays clinical and technical
      investigations. Some important aspects of the assessment of the physical damages
      according to the Belgian law are discussed.

PMID- 8266752
TI  - Vertical axillary thoracotomy; a muscle-sparing approach for routine thoracic
      operations.
AB  - A standard posterolateral thoracotomy with division of the latissimus dorsi and
      serratus anterior muscles is associated with an important postoperative
      morbidity. A vertical axillary thoracotomy combining a vertical axillary skin
      incision with an intermuscular approach sparing both latissimus dorsi and
      serratus anterior muscles has the advantage of allowing full shoulder girdle
      motion early postoperatively as well as masking of the scar by the upper arm at
      rest. We report our experience with nine patients operated on with this approach
      for various intrathoracic lesions. All procedures were carried out without major
      difficulties. Wound healing was excellent in all patients. No infection nor
      seroma formation was seen with a submuscular suction drain. All patients had
      early and full shoulder girdle movement. No patient complained of late post
      thoracotomy pain. We conclude that a vertical axillary thoracotomy provides an
      excellent cosmetic and muscle sparing incision which can be utilized for many
      thoracic procedures. However, we believe that, in the near future, video-assisted
      thoracoscopic surgery will become more popular than open thoracotomy for certain
      indications because of its distinct advantages of less postoperative morbidity.

PMID- 8266753
TI  - Total anomalous pulmonary venous connection. Results of a small consecutive
      series.
AB  - The surgical experience in 13 infants with total anomalous pulmonary venous
      connection (TAPVC) between 1987 and 1991 is reviewed. The age vary from 2 days to
      35 months with a weight at intervention from 2.130 kg to 5.400 kg. The types of
      TAPVC were supracardiac in 4 patients, cardiac in 4, and infracardiac in 5. Seven
      patients (54%) were operated on in emergency. Cardiopulmonary bypass consisted of
      profound hypothermia and total circulatory arrest in 8 patients (60%) and
      continuous hypothermic bypass with low flow for the remaining 5 patients (40%).
      There was no operative death. The follow-up ranges from 21 to 58 months, mean 40
      months. There was one reoperation. All the patients were asymptomatic and the
      height growth percentile is less than 5% in 20%, and the weight growth percentile
      is less than 5% in 30%. The early repair of infants born with TAPVC can be done
      with low morbidity with a good prospect on medium term follow-up.

PMID- 8266754
TI  - Intrathoracic ganglioneuroma: case report.
AB  - Ganglioneuromas are rare, benign neoplasms, arising from the sympathetic nervous
      system. The posterior mediastinum is the most common location of this neurogenic
      tumour. We present this case because of the problem of its diagnosis. Our patient
      had in fact been under observation for about twenty years. The size of the tumour
      caused a restriction of the pulmonary function.

PMID- 8266755
TI  - Pyogenic liver abscess. Diagnostic and therapeutic approach: a case report.
AB  - We report a case of liver abscess secondary to an asymptomatic, subacute
      appendicitis in a 51-year-old man. The general condition of the patient was
      altered but there were no gastrointestinal signs. Treatment consisted in broad
      spectrum antibiotics, followed by surgical drainage of the abscess and
      appendicectomy.

PMID- 8266756
TI  - Caroli's disease: a surgical dilemma.
AB  - We report the case of a 31-year-old male patient with a diffuse form of Caroli's
      disease presenting as recurring bouts of biliary pancreatitis. Following
      sphincterotomy, the patient remained asymptomatic for 5 years. He then developed
      acute cholangitis and, at laparotomy, all superficial liver cysts were
      fenestrated in order to remove intrahepatic bile duct calculi. A right
      hepatectomy, removing the most severely affected liver parenchyma was not
      considered feasible because of the small size of the left lobe and the existence
      of an associated congenital hepatic fibrosis. In diffuse forms of Caroli's
      disease biliary drainage techniques have often proved ineffective in preventing
      recurring bouts of cholangitis. Moreover, liver resection is seldom feasible
      because of associated congenital hepatic fibrosis. In this setting, liver
      transplantation may represent the only effective and durable form of treatment.

PMID- 8266757
TI  - Pancreatic localization of a Castleman's tumour.
AB  - Castleman's tumour is a rare anatomo-clinical entity. Most cases of Castleman's
      tumour occur in the mediastinum. The histopathology demonstrates benign
      angiofollicular lymph node hyperplasia. The pancreatic localization is uncommon
      and has only been reported once. We describe a new case with literature review.

PMID- 8266758
TI  - Gardner syndrome and desmoid tumors.
AB  - Desmoid tumours present difficult management problems in patients with Gardner's
      syndrome. We recently studied two patients with Gardner's syndrome, who developed
      a desmoid tumour arising of the abdominal wall and mesenteric root. One patient
      had a total resection of the mesenteric desmoid tumour followed by postoperative
      radiotherapy. No recurrence occurred in the last three years. The other patient
      had an incomplete resection and refused postoperative radiotherapy. Abdominal CT
      scan revealed tumour expansion 6 months postoperatively. From our experience and
      with respect to current literature, we suggest that complete surgical excision
      combined with radiotherapy (4.000-6.000 rads) could diminish the recurrence rate
      of desmoid tumours. When resection is incomplete or technically impossible,
      radiotherapy remains the second choice of treatment.

PMID- 8266759
TI  - Echographic characterization of carotid plaques.
AB  - The histology of the endarterectomy specimen was compared with the preoperative
      echopattern of 154 plaques. Thirty-four ultrasound images were of poor quality.
      The 120 adequate echographies revealed 22 dense hyperechogenic homogeneous
      plaques, 28 soft hypoechogenic homogeneous plaques, 53 inhomogeneous plaques, and
      13 mixed plaques. According to the surface, lesions were subdivided as smooth (n
      = 63) or irregular (n = 57). Echography recognized fibrous plaques (dense
      homogeneous hyperechogeneous lesions), with a specificity of 87% and a
      sensitivity of 56%. Recent intraplaque haemorrhage is echographically apparent as
      a hypoechogenic area in 88% of cases, what corresponds to a specificity of 79%
      and a sensitivity of 75%. Echography proved to be more accurate than angiography
      in determining the presence or absence of ulceration. The ability to characterize
      the pathology of carotid atheroma by duplex scan make the clinicopathologic
      correlation of carotid plaques of practical importance.

PMID- 8266760
TI  - Combined carotid and coronary revascularization.
AB  - A series of 295 patients with combined extracranial and coronary
      revascularization procedures is analyzed. Operations were combined in patients
      with symptomatic or severe carotid lesions. Hospital mortality was 3.5%; hospital
      morbidity was mainly neurological with 5% reversible neurological deficits or
      strokes. The independent risk factors for hospital mortality and morbidity as
      well as for long-term survival and morbidity were statistically analyzed. The 10
      year survival was 47% and predominantly determined by the cardiac 10-year
      survival (61%).

PMID- 8266761
TI  - Iliac artery stenosis after kidney transplantation.
AB  - In human kidney transplantation hypertension and renal dysfunction are common
      complications. Diagnosis of vascular involvement may frequently be necessary.
      Although iliac artery stenosis is a rare complication after renal
      transplantation, it can be the cause of hypertension and renal dysfunction.
      Because colour duplex scanning is a repeatable non-invasive technique, it may
      provide a useful tool in establishing a diagnosis of iliac artery stenosis in
      patients with hypertension and/or renal dysfunction. We present four cases of
      iliac artery stenosis in kidney allograft recipients. Colour duplex scanning was
      used in these patients to detect and localize the stenosis. Quantitative analysis
      of Doppler spectra was used to compare the Doppler spectrum waveforms obtained
      from both femoral arteries and from the kidney allograft arteries of these
      patients with the normal range. This normal range was determined from Doppler
      spectra obtained in a control group of 21 kidney allograft recipients. Clinical
      data, arterial DSA, and the outcome of treatment were used to validate colour
      duplex findings in the patients with iliac artery stenosis. Quantitative analysis
      of Doppler spectra showed differences between the femoral artery on the affected
      side and the contralateral side outside the normal range. In three patients the
      iliac artery stenosis was located proximal from the anastomosis with the kidney
      allograft artery and in these three patients Doppler parameters obtained from the
      allograft artery were also outside the normal range. In one patient the stenosis
      was located distally from the anastomosis with the kidney allograft artery. In
      this case Doppler spectra from the kidney allograft artery were within the normal
      range.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266762
TI  - Fibromuscular dysplasia of the superficial femoral artery: an unusual
      localization.
AB  - The authors describe an uncommon localization of fibromuscular dysplasia in the
      superficial femoral artery. The treatment consisted in surgical resection of the
      lesion. The follow-up showed extension of the disease. Review of the literature.

PMID- 8266763
TI  - [Digestive hormone receptors: current physiopathological and therapeutic
      aspects].

PMID- 8266764
TI  - [Mechanisms in hypergastrinemia in autoimmune atrophic gastritis and Helicobacter
      pylori infection].
AB  - The authors review recent progresses made in the understanding of the disturbed
      gastrin homeostasis in Helicobacter pylori infection and in pernicious anaemia.
      Regulation of gastrin release in a complex mechanism involving inhibition by a
      low gastric pH and several peptides including somatostatin, and stimulation by
      different factors, mainly alimentary peptides and amino-acids. The
      hypergastrinaemia observed in patients with Helicobacter pylori infection occurs
      despite a normal intraluminal pH. This may be through alkalinisation of the
      gastric mucus layer due to the production of ammonia by the bacterial urease or
      through local release of inflammatory mediators. In pernicious anaemia a factor
      present in the antacid gastric juice could explain the important
      hypergastrinaemia observed. The gastrin releasing activity of the gastric juice
      itself was demonstrated by a decrease of the patients' plasma gastrin
      concentration during a neutral gastric lavage and by a rise of the gastrin levels
      in rats whose stomachs were perfused with gastric juice from pernicious anaemia
      patients. A better understanding of the relation between gastric pH and gastrin
      release is important not only for these pathological states but also for
      treatments which suppress acid secretion.

PMID- 8266765
TI  - CCK/gastrin antagonists--clinical perspectives.
AB  - There are (at least) two types of receptor for cholecystokinin (CCK)/gastrin
      peptides. Highly potent specific antagonists are available for both types. The
      CCKA-receptor mediates classical CCK-like effects on the gut. Antagonists given
      to man inhibit pancreatic enzyme secretion and generally shorten gastrointestinal
      transit times. Potential clinical indications include anorexia, gastro-paresis,
      pseudo-paresis, pseudo-obstruction, severe constipation and chronic pancreatitis.
      However gallbladder contraction is markedly inhibited and this led to gallstone
      formation in baboons. This will obviously have to be avoided if CCKA antagonists
      are to be used in man. CCKB-receptors mediate the effects of gastrin on the gut
      and the effects of CCK in the brain. They inhibit gastrin-stimulated acid
      secretion. If used in acid-peptic disease they might inhibit the trophic effects
      of gastrin on enterochromaffin cells. CCKB-antagonists can also inhibit the
      growth of some gastrin-dependent tumours, including certain human colonic cancer
      cell lines which produce gastrin. CCKB-antagonists have a potent anxiolytic-like
      effect in animals, and this effect might become their main clinical application.

PMID- 8266766
TI  - Agonist effect of erythromycin and its analogues on motilin receptors. A new
      family of prokinetics? Clinical interest.
AB  - It has been known since long that erythromycin may cause unpleasant gastro
      intestinal side-effects such as nausea and vomiting. Recent studies however show
      that at low doses erythromycin may have a beneficial effect. Erythromycin induces
      the migrating motor complex in the fasted state and after a meal it accelerates
      gastric emptying. Although largely preliminary, its effects on esophageal, small
      intestinal, colonic and biliary tract motility have now been studied in several
      pathological conditions. Erythromycin is certainly a powerful gastrokinetic. Its
      antibiotic properties are a disadvantage, but more powerful derivatives devoid of
      antibacterial properties may soon become available. They form a new family of
      prokinetics.

PMID- 8266767
TI  - Current status on chromogranin A and pancreastatin.
AB  - The authors review the biochemical and biological properties of chromogranins and
      pancreastatin. Chromogranins A, B and C are acidic proteins of a molecular mass
      of 48,000, 76,000 and 67,000, respectively, located in the secretory granules of
      the neuroendocrine cells. Since large amounts of chromogranin A were found in
      most neuroendocrine tumours, chromogranin A plasma determination is a diagnostic
      tool even in silent tumours. Pancreastatin is a peptide derived from chromogranin
      A, which inhibits insulin secretion, exocrine pancreatic secretion and gastric
      acid secretion, and which stimulates glucagon secretion. Pancreastatin has
      different molecular forms, the major form being a high molecular form of 92 amino
      acids, found by the authors in human stomach- and colon extracts and in a liver
      metastasis of a gastrinoma. The controlled proteolysis of chromogranin A in gut
      neuroendocrine cells generates predominantly the high molecular weight form.

PMID- 8266768
TI  - [Current morphological methods in the study of endocrine tumors and their
      receptors].
AB  - The authors review the recent development of methods aimed at characterizing
      endocrine tumours. With new immunocytochemical methods, not only specific
      hormonal peptides can be identified but also hormonal precursors and their sites
      of processing. Immunodensitometry allows to quantify the hormonal cellular load
      and to assess hormonal synthesis via the precursors. Finally hormonal receptors
      can be identified by various techniques of autoradiography.

PMID- 8266769
TI  - Octreotide and postoperative enterocutaneous fistulae: a controlled prospective
      study.
AB  - Nineteen patients with postoperative enterocutaneous fistulae were randomised, in
      a double blind fashion, to receive either 12 days of octreotide (100 micrograms
      tds) by subcutaneous injection or 12 days of placebo injections. Fistula output
      for 7 days before and during all 12 days of treatment was recorded for each
      patient. Fistula losses before entering the trial were similar for both the
      placebo group (n = 8; range of daily medians: 202 mls to 400 mls) and the group
      of patients randomised to receive octreotide (n = 11; range of daily medians: 252
      mls to 550 mls). There was no significant difference in fistula output between
      the two groups of patients while receiving either 12 days of placebo injections
      or 12 days of subcutaneous octreotide therapy. Fistula closure, defined as no
      fistula output for 2 successive days during the 12 days "therapy" period, was
      seen in only 1 patient given octreotide and in 3 patients given the placebo. In a
      double blind prospective study of 19 patients with enterocutaneous fistulae,
      octreotide therapy was neither associated with a significant reduction in fistula
      losses nor an increased rate of spontaneous fistula closure.

PMID- 8266771
TI  - Use of octreotide in the treatment of digestive neuroendocrine tumours. Seven
      year experience in 20 cases including 9 cases of metastatic midgut carcinoid and
      5 cases of metastatic gastrinoma.
AB  - The authors report their experience with octreotide in 20 patients (median age 57
      years, 10 M, 10 F) from 1984 to 1991; 16 had metastatic APUDoma: 1 PPoma with
      VIPoma, 1 glucagonoma, 5 gastrinoma including 1 associated to PP-oma, 9 mid-gut
      carcinoid; 3 patients had multiple-endocrine neoplasia type I (MEN-I) with
      Zollinger-Ellison syndrome (ZES) and 1 patient a non-metastatic VIPoma.
      Octreotide (200-750 micrograms/day) was administered bid or tid with regular
      laboratory controls and morphological assessment. There was a striking
      improvement of symptoms, particularly in the carcinoid group (reduction of
      flushing in all patients and of diarrhoea in 3/5), in the patient with gastrinoma
      + acromegaly (regression of congestive heart failure) and in the patient with non
      metastatic VIPoma. The hormonal markers were markedly reduced, particularly
      gastrin, PP (except in the patient with PPoma + VIPoma), VIP, GH and Somatomedin
      C and urinary 5HIAA in 4/9 patients with carcinoid. There was only one partial
      regression of metastases (gastrinoma) and 4 apparent stabilizations of tumour
      growth, in the 16 metastatic cases. Among them, 4 patients died: 1 glucagonoma, 1
      PPoma + VIPoma, 2 mid-gut carcinoids after a treatment of 5, 16, 30, 36 months,
      respectively. The patient with acromegaly + ZES died after 6 years of treatment
      at age 81. A patient with prolactinoma, resected insulinoma, hyperparathyroidism
      and ZES was not improved by a short course of octreotide (hypoglycemia); he died
      later of recurrent insulinoma. In conclusion, octreotide is a useful drug to
      control most of the symptoms related to gut endocrine tumours; it may inhibit
      tumour growth.

PMID- 8266770
TI  - Inhibition of pancreatic secretion to prevent postoperative complications
      following pancreatic resection.
AB  - Major pancreatic resection still nowadays carries a considerable risk for
      morbidity and even mortality. Complications occurring after pancreatic surgery
      are chiefly linked with exocrine pancreatic secretion. Therefore to inhibit
      exocrine pancreatic secretion perioperatively, seems to be a promising concept in
      the prevention of complications following pancreatic resection. The hormone
      somatostatin and its synthetic analogue octreotide have been demonstrated to
      inhibit exocrine pancreatic secretion profoundly, particularly the secretion of
      proteases is decreased. In a randomized placebo-controlled multicentric and
      double blind trial we analysed the role of octreotide in the prevention of
      postoperative complications after major pancreatic surgery. A significant
      reduction of complications (fistula, abscess, fluid collection, sepsis, pulmonary
      insufficiency, postoperative acute pancreatitis) could be demonstrated in
      patients receiving octreotide (3 x 100 micrograms per day sc.). The effect of
      octreotide was particularly true in patients undergoing a Whipple resection for
      cancer.

PMID- 8266772
TI  - Repeated hepatic ischemia in combination with chemotherapy for liver carcinoid
      metastases.
AB  - Both hepatic ischemia and chemotherapy are effective in the treatment of
      carcinoid liver metastases, but their effectiveness is often limited, partial and
      transient. It has been shown that, during intermittent occlusion of the hepatic
      artery with a surgically implanted occluder, no revascularisation from
      collaterals occurs. We studied the feasibility, the side-effects, the response to
      tumour measurements and hormonal excretions of a combined treatment of repeated
      hepatic ischemia and 5-Fluorouracil and Streptozotocin-administration in
      carcinoid liver metastases.

PMID- 8266773
TI  - AANA testifies before PPRC on federal healthcare reform.
AB  - The AANA shares President Clinton's view that health system reform must center on
      increased patient access to care, the need for care to be provided in a cost
      effective manner, and that quality of care should not be diminished. The AANA
      believes that CRNAs can play a critical role in health system reform because for
      more than a century they have provided a model of how patients can have access to
      high quality, cost-effective health services, specifically anesthesia services.

PMID- 8266774
TI  - Baptist Medical Center Montclair v Wilson.

PMID- 8266775
TI  - Assessing the potential for awareness and learning under anesthesia.
AB  - The problems of intraoperative learning and awareness during surgery have
      consequences for both the patient and the medical team. With or without recall,
      the patient can suffer severe emotional trauma that may result in psychological
      damage. Successful litigation against the anesthesia professional has been
      increasing in numbers as failure to provide adequate anesthesia can be considered
      a breach of the unwritten contract between patient and anesthetist. Balanced
      anesthesia and its use of muscle relaxants can mask indicators of anesthesia
      depth such as movement or lacrimation. To date, means of monitoring real-time
      levels of intravenous agents have not yet been fully tested and proven.
      Therefore, monitoring minimum alveolar concentrations of inhaled anesthetics may
      be the best currently available method of ensuring anesthetic depth.
      Investigations comparing the correlation between nitrous oxide and isoflurane
      minimum alveolar concentrations and anesthetic depth have indicated specific
      levels at which intraoperative learning ceases to occur.

PMID- 8266776
TI  - Some thoughts on student nurse anesthetist eligibility for workers' compensation.

PMID- 8266777
TI  - AANA Journal course. 5: Update for nurse anesthetists--essential hypertension,
      anesthesia, and the kidney.
AB  - Intraoperative systemic and renal hemodynamics are unpredictable in patients with
      essential hypertension due to their pharmacologic management, as well as the
      underlying disease process itself. The purpose of this review is to explore
      possible mechanisms mediating essential hypertension and describe the
      ramifications of various therapeutic interventions. Understanding the integrated
      relationship between blood pressure and the kidney will optimize intraoperative
      management of patients with essential hypertension.

PMID- 8266778
TI  - Paroxysmal atrioventricular block in a healthy patient receiving spinal
      anesthesia: a case report.
AB  - The presentation of type 1, second-degree atrioventricular block (AVB) in a
      young, healthy patient is rare. This article describes such an event in a 36-year
      old white male under subarachnoid block (SAB) anesthesia. At 25 minutes into
      surgery, the pulse oximeter and the ECG monitor both alarmed for nonsensing and
      asystole, respectively. The patient had experienced a complete AVB. "Cough
      cardiopulmonary resuscitation (CPR)" was begun, and the patient was instructed to
      take deep breaths and cough as hard as possible. During the entire duration of
      the AVB, the patient never lost consciousness and continued cough CPR, with
      encouragement from the author. Ephedrine 12.5 mg in two doses was administered
      through the rapidly infusing intravenous line. The patient was continued on
      oxygen, as described, and the pulse oximeter continued to demonstrate a
      saturation greater than 96% during the entire event. After approximately 40
      seconds, the patient's rhythm changed to a type 1, second-degree AVB. After an
      additional 15 minutes, the patient's sinus rhythm returned to normal. This event
      emphasizes the value of vigilance. Continuous monitoring, including pulse
      oximetry, blood pressure measurements, and continuous ECG, should be used on all
      patients receiving any form of anesthesia.

PMID- 8266780
TI  - Council on Accreditation of Nurse Anesthesia Educational Programs.

PMID- 8266779
TI  - Cardiovascular collapse associated with the use of methylmethacrylate.
AB  - Methylmethacrylate has been used extensively in the United States since 1971 for
      the fixation of orthopedic prostheses. A chemical compound that generates a
      considerable amount of heat as it sets and hardens, it has been known to cause
      mild to moderate hypotension as well as cardiovascular collapse and death in some
      instances. Some of the purported etiologies of the untoward effects of
      methylmethacrylate include fat embolism, air embolism, bone marrow embolism,
      peripheral vasodilation, activation within the lungs of the clotting cascade,
      direct cardiovascular depressant effects of methylmethacrylate cement or monomer,
      and others. In this article, the use of methylmethacrylate in orthopedic
      procedures is reviewed, along with a discussion of some of the previously
      hypothesized causes of its side effects. Then a case report of its use in a 59
      year-old woman with a pathological fracture of her left femur is presented.
      Finally, the implications for the anesthetist are noted, and suggested
      interventions to limit untoward effects with the use of methylmethacrylate are
      presented.

PMID- 8266782
TI  - Preoperative electrical stimulation for cochlear implant selection. The use of
      ear canal electrodes versus transtympanic electrodes.
AB  - Preoperative electrostimulation tests were performed on 43 postlingually deaf and
      20 prelingually deaf cochlear implant (CI) candidates. The stimulating electrode
      was placed at three different locations, i.e. the round window, the promontory
      and the ear canal and the results were compared. The evoked sensations were
      reported to be of auditory origin by most of the postlingually deaf CI
      candidates. Prelingually deaf subjects could not always distinguish clearly and
      reliably between "hearing" and "feeling". The percentage of stimulated ears of
      postlingually deaf subjects in whom hearing sensations were evoked was almost
      identical for the three locations of the stimulating electrode. However, in 5 out
      of the 7 ears without hearing sensations during ear canal stimulation (ECS),
      hearing sensations could be evoked during either promontory stimulation (PS) or
      round window stimulation (RWS). The mean threshold level for "hearing" at a
      stimulation frequency of 62 Hz was lowest during RWS, 7.7 dB higher during PS and
      35.8 dB higher during ECS. The mean electrical dynamic range at 62 Hz was most
      favourable during RWS (23.9 dB), smaller during PS (15.6 dB) and smallest during
      ECS (10.0 dB). All differences were statistically significant. Placement of the
      ear canal electrode was easier, less frightening for the patient and required
      less time than insertion of the needle electrode for PS or RWS. Therefore we
      recommend the use of ECS to examine whether the CI candidate can be stimulated,
      and of RWS if more detailed information is required.

PMID- 8266781
TI  - HLA associations with Meniere's disease.
AB  - In order to investigate the genetic background of Meniere's disease,
      histocompatibility (HLA) antigens in Japanese patients were studied. HLA-class I:
      HLA-A, -B and -C were typed by the classical microcytotoxicity technique, and HLA
      class II: HLA-DR, DQ, and DP were typed by PCR-DNA typing methods. Twenty patient
      samples tested were selected very strictly following clinical data and classical
      criteria. Most of the patients had been suffering from typical symptoms during a
      considerably long period of time (16 +/- 7 years). Normal controls were based on
      the gene frequency in the Japanese population. Compared with the normal controls,
      a higher frequency of the DRB1*1602 subtype of HLA-DR2 was found in the patient
      group (chi 2 = 9,21, p < 0.04). P-values were corrected by multiplying by the
      total number of antigens. Additionally, HLA-Cw4 was increased, although the p
      value was not significant after multiple antigen correction. There was no obvious
      relationship between the HLA-DRB1*1602 patients and the clinical data that
      included severity, age at time of onset, etc.

PMID- 8266783
TI  - Stimulus-inadequate sensations in cochlear implant patients.
AB  - From August 1984 to April 1987 the Department of Otolaryngology at the
      Medizinische Hochschule in Hannover implanted the NUCLEUS 22 channel cochlear
      implant system (CI) in their first 56 adults. Since implantation, 27 (51%)
      patients have described undesirable sensations from their implant. These were
      defined as stimulus-inadequate sensations (SIS) and were classified into three
      types: 1) pain-like sensations; 2) high-frequency sensations; and 3) non
      stimulation. Twenty-three patients were radiographically investigated by
      polytomography. All of the intracochlear electrodes were visualised and a
      correlation between SIS and the radiological findings was established. It was
      found that i) SIS similar to pain are caused by electrical stimulation of the
      mucous membranes and periosteum of the tympanic cavity; ii) the high-frequency
      SIS seemed to be due to non-physiological electrical stimulation of the basal
      ganglion cells; and iii) the reason for non-stimulation is probably damaged
      electrodes and fibrosis around the electrode. Conventional tomography is the
      method of choice for estimating the number and configuration of intracochlear
      electrodes.

PMID- 8266784
TI  - Spontaneous cellular vibrations in the guinea-pig cochlea.
AB  - Mechanical vibrations of Hensen cells were measured with a laser-heterodyne
      interferometer in the third turn of the guinea-pig temporal-bone preparation
      without the application of an external stimulus. Smoothed periodograms (spectral
      density estimates vs frequency) were constructed from the velocity vs time
      waveforms recorded from individual cells. For some cells, several peaks appear in
      the periodograms at levels as high as 10 dB above the noise floor, indicating the
      presence of spontaneous vibrations. The frequencies at which the peaks are
      located differ in different preparations, indicating that the observed peaks are
      not caused by the presence of ambient noise or ambient vibrations. It is
      demonstrated that smoothed-periodogram analysis is superior to fast-Fourier
      transform analysis for discerning these spontaneous spectral components. The
      frequency tuning curves of cells from which spontaneous vibrations were measured
      (determined by applying an external stimulus to the ear) have single principal
      peaks. When the spontaneous spectral features are present, their frequencies lie,
      for the most part, within the principal-peak region of the tuning curve. We
      propose that these spontaneous vibrations originate at the outer hair cells and
      are the source of spontaneous otoacoustic emissions in the ear.

PMID- 8266785
TI  - Efferent vestibular fibers to otolith organs in guinea pigs.
AB  - The origins of efferent vestibular fibers to the otolith organs in guinea pigs,
      examined with the use of retrograde transport of HRP were: i) the bilateral
      lateral portions of the facial genu and ii) the ipsilateral reticular nucleus at
      the level of the facial nucleus. These origins are almost the same as those of
      the efferent fibers to the three semicircular canals which we have previously
      identified in cats; however, they differ in certain respects.

PMID- 8266786
TI  - Distribution of calcitonin gene-related peptide mRNA and immunoreactivity in the
      rat central and peripheral vestibular system.
AB  - The distribution of calcitonin gene-related peptide (CGRP) mRNA and
      immunoreactivity (CGRPi) was examined in sections of brainstem and decalcified
      temporal bones to study the peptidergic innervation patterns in both the central
      and peripheral vestibular system. In the brainstem, neuron somata associated with
      the vestibular system and containing CGRP mRNA and CGRPi were found in both the
      dorsolateral and medial regions of the group E vestibular efferents as well as
      scattered throughout the caudal pontine reticular nucleus (CPR). The only
      labelled neuron somata containing CGRP mRNA and CGRPi in the temporal bone were
      found in the gustatory geniculate ganglion. Coarse CGRPi axons were traced
      ventrally from the dorsolateral and medial group E somata and dorsally from the
      CPR somata. CGRPi axons from the medial group E and CPR crossed the facial nerve
      ventral to the facial genu before entering the eighth nerve root. Immunoreactive
      axons projected from medial group E cells, beneath the ependyma of the fourth
      ventricle, to the contralateral brainstem. Unmyelinated CGRPi fibers passed among
      the primary afferent fibers in Scarpa's ganglion and continued through the
      subepithelial regions of the vestibular end-organs. Within the neurosensory
      epithelia of the maculae and cristae, the CGRPi axons ramified to produce
      numerous CGRPi terminals. An efferent neuromodulatory role of CGRP in the
      vestibular system is inferred from the wide distribution of CGRP mRNA and
      immunoreactivity found within efferent vestibular neurons.

PMID- 8266787
TI  - Provoked flux motion of cochlear blood flow measured with laser Doppler flowmetry
      in guinea pig.
AB  - Although progress has been made in the study of cochlear blood flow (CBF)
      regulation since laser Doppler flowmetry (LDF) was introduced, cochlear
      vasomotion has not been investigated. Therefore, the primary objective of this
      study was to determine if oscillatory fluctuations of CBF could be provoked.
      Guinea pigs were anesthetized with diazepam (5 mg/kg) and fentanyl (0.32 mg/kg).
      Blood pressure (BP) was recorded from a carotid artery cannula. The cochlea and
      pons cerebellum were ventrally exposed; the bilateral CBF and brain blood flow
      (BBF) or skin blood flow (SBF) were monitored by LDF. After administration of
      phentolamine (0.25-0.75 mg/kg, i.v.), ipsilateral CBF in 7 of 16 animals showed a
      2-5 min episode of oscillation. During artificial hyperventilation, continuous
      oscillation of CBF was recorded (the flux motion frequency was 3.5 +/- 0.5 cycles
      per min and its amplitude 25.8 +/- 5.6% from baseline). The time-dependent flux
      change (the waveform) was the same throughout a single cochlea but different
      between cochleae of the same animal. Compared to BBF, CBF vasomotion frequency
      was lower, and amplitude larger. SBF exhibited no such motion. Flux motion could
      be eliminated by inhalation of pure oxygen or 5% CO2 in oxygen or by the smooth
      muscle relaxants, papaverine and hydralazine. Phentolamine-induced vasomotion may
      be due to a hypotensive perfusion pressure, and hyperventilation-enhanced
      vasomotion may be caused by changing blood gas concentrations and by hormonal or
      neuronal activity. Oxygen and CO2 inhalation slightly increased BP and this
      change in perfusion pressure was probably associated with weakened
      vasomotion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266788
TI  - Secretory component and IgA in the endolymphatic sac.
AB  - Immunohistochemical methods were used to investigate secretory component (SC) and
      immunoglobulin A within the inner ears of Sprague Dawley rats and BALB/c mice.
      Utilizing specific antisera against SC and IgA, the distribution and localization
      of SC and IgA were studied in normal, non-immunized ears of both animal species.
      The kinetics of SC and IgA were also investigated during a secondary immune
      response following keyhole limpet hemocyanin (KLH) challenge of murine inner
      ears. In the non-immunized murine inner ear, neither SC or IgA were found. In
      contrast, SC was localized within the epithelial cells and lumen of the
      endolymphatic sac (ES) in non-immunized rats and faint luminal IgA staining was
      seen in one-third of the animals, as well as an occasional IgA-bearing cell in
      the ES. In the inner ear secondary immune response, SC was found only within the
      endolymphatic sac of approximately 50% of the immunized mice 14 days after KLH
      challenge. IgA-bearing cells were also observed within the ES 2 to 3 weeks
      following KLH challenge. We conclude that there are species differences in the
      distribution of SC and IgA within the inner ear, and that under pathological
      conditions the endolymphatic sac may be a site of IgA and SC induction.

PMID- 8266789
TI  - Osteogenesis imperfecta: clinical symptoms and update findings in computed
      tomography and tympano-cochlear scintigraphy.
AB  - Osteogenesis imperfecta (OI) is an autosomal-dominantly inherited connective
      tissue disorder characterized by abnormal bone fragility combined with blue
      sclerae. The association of OI with hearing impairment is commonly known as Van
      der Hoeve-de Kleyn syndrome. Besides typical symptoms we here report on findings
      by high resolution CT and by high resolving scintigraphy of the labyrinthine
      capsule in 3 families (9 patients) with OI, which resemble those in otosclerosis
      (OS): In 4 of 6 cases with OI and mixed hearing loss, severely decreased peri
      cochlear bone density was established by CT. In these cases, increased bone
      metabolism could be revealed by high resolving tympano-cochlear scintigraphy
      (TCS) in the cochlear region. In 2 patients with mixed hearing loss and 3 cases
      without hearing impairment or with slight conductive hearing loss, bone
      alteration was not detectable by CT and TCS. These results raise the question
      whether OI and OS lead to similar labyrinthine bone alterations, based on
      different aetiologies or whether these diseases may co-exist, OS being part of
      OI.

PMID- 8266790
TI  - Clinical relevance of magnetic resonance imaging and computed tomography in
      Cogan's syndrome.
AB  - The Pathologic changes in the inner ears of 5 patients with Cogan's syndrome were
      studied by a combined application of MR imaging and CT scanning. We used T1- and
      T2-weighted MR imaging sequences and a special three-dimensional MR imaging
      technique which allows a very detailed imaging of the inner ear structures. By
      the use of a CT scan simultaneously, calcified and noncalcified obliterations
      could be differentiated. The aim of the study was to visualize membranous
      labyrinth pathology in Cogan's syndrome and correlate them with the clinical
      findings. In one patient who recovered completely without hearing loss, the MR
      and CT investigations revealed no pathology. In the remaining 4 cases, narrowing
      or obliteration of parts of the vestibular labyrinth was seen. In 3 patients, we
      found aberrations in the cochlea consistent with the audiological data. The
      gadolinium-enhanced T1-images showed enhancement of the cochlea and vestibular
      labyrinth in one case, probably indicating an active process with interruption of
      the "blood-labyrinth barrier". The results are consistent with the hypothesis
      that the inner ear pathology in Cogan's syndrome is probably caused by
      obstructive vasculitis.

PMID- 8266791
TI  - Ultrastructural arrangement of collagen fibrils in the rat facial nerve.
AB  - We studied the collagen fibril arrangement in the connective tissue sheaths
      (epineurium, perineurium, and endoneurium) of the intratemporal and extra
      temporal portion of the rat facial nerve by transmission electron microscopy
      after fixing the nerves with tannic acid, and by scanning electron microscopy
      after digesting cellular elements by sodium hydroxide treatment. These studies
      revealed that the epineurium consists of thick bundles of collagen fibrils and a
      coarse meshwork of collagen fibrils, the perineurium consists of a lacework sheet
      of bundles of collagen fibrils, and the endoneurium consists of a meshwork of
      fine collagen fibrils in the inner layer and of longitudinally oriented bundles
      of collagen fibrils in the outer layer. There was little difference in the three
      dimensional organization of collagen fibrils between the extra-temporal segment
      and vertical and horizontal segments of the facial nerve. However, the facial
      nerve lost the epineurium and perineurium in the central portion of the
      horizontal segment near the geniculate ganglion and in the labyrinthine portion,
      i.e. the proximal portion of the intratemporal segment. In these segments, the
      endoneurium consisted of a meshwork of fine collagen fibrils.

PMID- 8266792
TI  - Mechanics of the middle ear in otosclerosis and stapedoplasty.
AB  - Seventy-three otosclerotic patients, 138 subjects who had undergone stapes
      surgery (50 total stapedectomies, 43 stapedotomies with stapedius tendon section
      and 45 stapedotomies with stapedius tendon preservation) and 70 normal controls
      were investigated by susceptance multiple frequency tympanometry. The aims were
      to evaluate the efficiency of this procedure in diagnosing otosclerosis and to
      assess the resonance properties of middle ears undergoing different types of
      stapedectomy. Tympanometry was performed using sweep frequencies ranging from 226
      to 2,000 Hz for each pressure step of 12.5 daPa (pressure range from -500 to 400
      daPa). The resonance frequency of the system was evaluated by identifying the "W"
      morphology of susceptance tympanograms. The results of the present investigation
      indicate that stapes surgery abnormally reduces the stiffness of the tympano
      ossicular system. This phenomenon is limited by preservation of the stapedius
      tendon, which confers a significant degree of stiffness on the conductive system.

PMID- 8266793
TI  - Mucosal exudation of fibrinogen in coronavirus-induced common colds.
AB  - We studied the mucosal exudation of plasma in relation to pathophysiological
      events during an induced common cold. Coronavirus 229E was inoculated nasally in
      20 healthy volunteers under controlled conditions. Ten volunteers developed the
      common cold, determined by symptom scores and serology. The bulk plasma exudate
      was monitored, using fibrinogen (MW 340 kD) in nasal lavage fluids as an
      endogenous marker. Following inoculation, anterior rhinoscopy and objective
      registrations of nasal mucosal temperature, nasal discharge weight, and nasal
      blockage index by peak expiratory air flow, were followed twice daily for 6 days.
      Mucosal plasma exudation, as assessed by fibrinogen in lavage fluids, increased
      hundredfold after virus inoculation, concomitantly with the subjective symptoms
      and objective physiological changes. We propose that this exudation reflects the
      degree of subepithelial inflammation, and suggests that plasma bulk exudate,
      including all potent plasma protein systems may be involved in the resolution of
      acute viral rhinitis--common cold.

PMID- 8266794
TI  - Mechanical stimulation and capsaicin evoked vasodilation by parasympathetic
      reflex mechanisms in the pig nasal mucosa.
AB  - A model was developed using pentobarbital anesthetized pigs to study bilateral
      blood flow changes in the nasal mucosa by flow-probes on both sphenopalatine
      arteries. Unilateral mechanical stimulation of the nasal mucosa for 10s as well
      as close intra-arterial capsaicin infusion induced bilateral vasodilation. The
      magnitude of the vasodilator responses were similar on both sides, although the
      capsaicin effect (maximal increase in arterial blood flow by about 100 ml/min)
      was larger than that of the mechanical stimulation. Pretreatment with atropine
      (0.5 mg x kg-1) had no effect on the vascular responses to capsaicin or
      mechanical stimulation. However, when the pigs were pretreated with the
      ganglionic nicotinic receptor blocking agent, chlorisondamine (3 mg x kg-1), the
      vasodilatory responses to mechanical stimulation were abolished and the responses
      to capsaicin infusion markedly reduced (90-95%). These data indicate that
      unilateral mechanical stimulation as well as capsaicin infusion evoke bilateral
      nasal vasodilation which is probably mediated via a central reflex arch with a
      parasympathetic non-cholinergic final step.

PMID- 8266795
TI  - Effect of exogenous ATP on ciliary beat of human ciliated cells studied with
      differential interference microscope equipped with high speed video.
AB  - To study the detailed effects of exogenous adenosine triphosphate (ATP) on
      ciliary function, we used the differential interference microscope equipped with
      high speed video and evaluated ciliated cells from the human sinus mucosa in
      monolayer culture. With this system it was possible to evaluate all parts of
      ciliary motility with a minimum of interference from the mucous membrane,
      secretory cells and the autonomic nervous system. The best direct
      ciliostimulative effect of exogenous ATP on ciliary beat frequency (CBF) and
      ciliary beat amplitude (CBA) was observed at concentrations of ATP ranging from
      10(-5) M to 10(-3) M. Exogenous ATP appeared to normalize the slightly damaged
      ciliary motility in groups with an initial CBF of 14 Hz or higher. When the CBF
      was less than 14 Hz, ATP produced an increase in CBF greater than 40%, an
      increase in CBA greater than 30%, but these did not reach the normal level in 5
      min. The biggest increases: 59.9% in CBF and 40.7% in CBA were seen in the group
      with an initial CBF less than 9 Hz. In the cells with a low initial CBF and
      unsynchronized motility exogenous ATP increased the synchrony of ciliary movement
      together with an increase in CBF and CBA.

PMID- 8266796
TI  - Immunohistochemistry of Nasopharyngeal (Waldeyer's ring equivalent) lymphoid
      tissue in the rat.
AB  - Previously we have described the presence of Waldeyer's ring equivalent (WRE)
      lymphoid tissue in the rat, and pointed out the importance of such an
      experimental model for studying the immunological role of nasopharyngeal lymphoid
      tissue. Here we extend this work with immunohistological data in terms of
      compartmentalization and distribution of the various lymphoid and non-lymphoid
      cells of this WRE lymphoid tissue in situ. WRE tissue consists of distinct T cell
      and B cell areas. B cell areas predominate; they are located directly under the
      mucosal epithelium and consist mainly of follicles. These follicles frequently
      contain a germinal center with IgD negative B cells interspersed with scattered
      CD4 (helper/inducer) T cells. Follicular dendritic cells are present in the
      germinal centers. T cell areas, on the other hand, are predominantly present at
      the abluminal side of the WRE in interfollicular areas. In these areas high
      endothelial venules and both CD4 and CD8 (suppressor/cytotoxic) T cell
      populations with a clear preponderance of CD4 over CD8 cells can be observed. MHC
      class II positive interdigitating dendritic cells are also scattered throughout
      these T cell areas. Mononuclear phagocytes (ED1-positive monocytes/macrophages)
      are scattered throughout the WRE, but especially in the T cell areas. A
      subpopulation of (ED3-positive) mononuclear phagocytes, e.g., the lymphoid tissue
      macrophage, is exclusively scattered between the small blood vessels along the
      abluminal side of the lymphoid tissue. Here, plasma cells, including those of the
      IgA type, are located. The data show that nasopharyngeal lymphoid tissue in the
      rat can be considered as an immunologically fully equipped and active mucosal
      lymphoid organ presumably executing similar immune functions as the tonsils in
      the human Waldeyer's ring.

PMID- 8266797
TI  - Quantitative bacterial culture from adenoid lymphatic tissue with special
      reference to Haemophilus [corrected].
AB  - Homogenized adenoid tissue from 55 children (28-153 months) undergoing
      adenoidectomy because of nasopharyngeal obstruction was investigated by means of
      quantitative aerobic bacterial culture. The children were divided into two
      groups, the hypertrophy alone group--AH (n = 29)--and the hypertrophy with
      longstanding secretory otitis media group--SOM (n = 26). A nasopharyngeal culture
      was obtained preoperatively from 38 of the cases. Non-typeable H. influenzae
      (NTHI) was found in twice as many cases in the AH group as in the SOM group,
      21/29 (72%) compared to 11/26 (42%) (p < 0.05) and in a significantly higher mean
      concentrations, 5.7 x 10(5) CFU/g compared to 1.9 x 10(5) CFU/g (p = 0.02). For
      the other aerobic potentially pathogenic bacteria no such difference was found.
      The bulk of the NTHI-positive cases and the cases with the highest concentrations
      were found in the children below the age of 6 years. In the nasopharyngeal
      cultures NTHI alone or together with S. pneumoniae and/or B. catarrhalis was
      found in 29% of the cases in both the AH group and SOM group. NTHI was found in
      only 50% of the nasopharyngeal cultures corresponding to a positive quantitative
      culture (10/20). These findings suggest that NTHI is harboured within the adenoid
      and could thereby chronically stimulate the local immune defense. However, the
      present study indicates that there is no aerobic bacterial overload in the
      adenoid tissue in children with SOM compared to children without middle-ear
      disease.

PMID- 8266798
TI  - Anti pneumococcal antibody activity in nasopharyngeal secretions in healthy
      adults and children.
AB  - The local antibody activity to Streptococcus pneumoniae serotype 6B was measured
      in nasopharyngeal secretions from 20 healthy adults and 43 children, 1-3 years of
      age, 14 of whom were healthy and 29 were at risk for developing recurrent
      episodes of acute otitis media (RAOM) according to the criteria described below.
      In children, anti pneumococcal IgA and IgG antibody activity was of the same
      magnitude in both groups. Adults showed significantly higher specific IgA
      activity. Antibody activity of the IgG isotype was also higher in adults,
      possibly reflecting the higher serum antibody levels. The children at risk of
      developing RAOM had significantly higher levels of secretory component (SC) in
      their nasopharyngeal secretions. Our data suggest that local immunity in the
      nasopharynx is not fully developed in young children, which might contribute to
      bacterial survival and colonization in the region.

PMID- 8266799
TI  - The intramuscular nerve supply of the human lateral cricoarytenoid muscle.
AB  - The lateral cricoarytenoid (LCA) muscle is one of the adductors of the vocal
      cords; however, some investigators believe that the lateral edge of the muscle
      may be involved in abduction. The possibility of functionally distinct
      compartments within the LCA was investigated by observing the pattern of the
      intramuscular nerve supply. This technique has previously clearly demonstrated
      neural compartments in the posterior cricoarytenoid, thyroarytenoid and
      cricothyroid muscles. Five adult human larynges were processed by the Sihler's
      stain which clears all soft tissue while counterstaining the nerves. The results
      of our study showed that the innervation pattern of the human LCA muscle is
      composed of a homogenous nerve plexus localized to the middle region of the
      muscle. This pattern correlates with the location of motor endplates described by
      prior investigators. The consistent neural pattern suggests that the LCA is
      composed of a single neuromuscular compartment.

PMID- 8266800
TI  - A device for measuring mucociliary activity in the human bronchi during fibre
      optic bronchoscopy.
AB  - An in vivo method for the study of mucociliary activity in the human trachea and
      bronchi is presented. The method is based on a two-way fibre-optic system whereby
      reflections of light emitted by one glass-fibre and reflected by the cilia are
      picked up by a second glass fibre and transmitted to a recording unit. The glass
      fibre system is designed to be used in conjunction with a regular fibre
      bronchoscope, and is convenient for routine use in daily clinical work. As
      reference material, 15 subjects aged 23-73 years without evidence of disease were
      examined in their right upper bronchus. The average cilial beat frequency was
      found to be 12.0 +/- 1.0 (SD) waves per second.

PMID- 8266801
TI  - [Parotid metastases: a review of the literature and case reports].
AB  - Parotid gland is an unusual metastasis site. Metastatic lesions very often
      represent spread from adjacent regions of lymphatic drainage; nevertheless direct
      involvement or hematogenous spread can occur. Head and neck cutaneous tumors are
      the most common primary: in a overlooking of more than 800 cases, cutaneous
      squamous cell carcinomas and melanomas represent about 80%. Parotid metastasis
      from extra-cutaneous head and neck tumors and distant primary are uncommon: in
      our review we found respectively 66 and 87 reports. In our experience, from 1968
      to 1991, we observed 38 patients with metastatic involvement of the parotid
      gland. The primary were located as follows: 24 cutaneous head and neck tumors (15
      SCC, 7 melanomas, 2 BCC), 10 extra-cutaneous supra-clavicular tumors (9
      carcinomas, 1 adenocarcinoma), 4 distant primary (2 renal cell carcinomas, 2 lung
      tumors). In 14 patients was performed a parotidectomy, in 10 cases associated to
      a neck dissection and in 4 cases followed by post-operative radiotherapy.
      Exclusive radiotherapy and chemotherapy were performed respectively in 14 and 4
      cases, in 6 patients the only planned treatment was a symptomatic therapy. After
      1, 3 and 5 years follow-up the overall survival was respectively of 71.4%, 30.4%
      and 11.8%; better results were observed in cutaneous primary (86.3%, 42.8% and
      20%). To conclude, parotid metastases represent a not uniform clinical entity.
      Cutaneous SCC, BCC and melanoma can be successfully treated by surgery and/or
      radiotherapy. As non-cutaneous secondary parotid tumors have a poor prognosis,
      treatment must be related to condition of generalized disease.

PMID- 8266802
TI  - Potassium currents in isolated human atrial and ventricular cardiocytes.
AB  - The whole-cell configuration of the patch-clamp technique was applied to study
      and compare ion currents in single ventricular and atrial cardiocytes isolated
      from human myocardium. In ventricular cardiocytes the K+ inward rectifier current
      (IK1) was three times larger than in atrial cardiocytes, while its inactivation
      kinetics were twice as slow when measured at -140 mV. The magnitude of these
      variables depended on the test potential but was independent of changes in
      holding potential. A transient outward current (I(to)) was observed in both
      ventricular and atrial cardiocytes. The amplitude of the inactivating component
      of Ito was not significantly different in atrial and ventricular cells, but the
      time course of inactivation was significantly longer in atrial than in
      ventricular cardiocytes. Steady-state inactivation of Ito in atrial cells was
      well described by a two-state Boltzmann function having a midpoint potential of 
      41.4 mV and a slope factor of 6.9 mV-1. No discernible K+ delayed rectifier
      current (IK) was observed in either cell type. In four of the 12 atrial cells
      studied, a time dependent inward current was observed at negative test potentials
      having a 240 +/- 21 ms time constant for activation and an amplitude of 101 +/-
      28 pA. This current, which resembled the pacemaker current (I(f)), was not
      observed in any of the ventricular cells examined.

PMID- 8266803
TI  - Substrate preference of isolated perfused rat hearts during hypothermia and
      rewarming.
AB  - Fatty acid and glucose oxidation rates were measured in isolated rat hearts
      undergoing hypothermia and rewarming. The hearts were perfused in the Langendorff
      mode with Krebs-Henseleit bicarbonate buffer containing 11.1 mM glucose plus 0.6
      mM albumin-bound oleic acid as energy substrates. The hearts were stabilized at
      37 degrees C and thereafter cooled progressively to 15 degrees C over a period of
      60 min. The hearts were kept at this temperature for 10 min and then rewarmed to
      37 degrees C during the next 30 min. Control hearts were perfused at 37 degrees C
      throughout the whole perfusion period. Trace amounts of [14C]glucose or
      [14C]oleic acid were included in the perfusate, and the rate of substrate
      oxidation was determined on the basis of the radioactive CO2 production. In
      normothermic hearts steady state oxidation rates of glucose and oleate were found
      to be 0.17 +/- 0.01 and 0.51 +/- 0.07 mumol min-1 g-1 dry wt, respectively (mean
      +/- SEM). In response to hypothermia (15 degrees C) glucose oxidation was reduced
      by 76% (from 0.17 +/- 0.01 to 0.04 +/- 0.01 mumol min-1 g-1 dry wt) and oleate
      oxidation by 47% (from 0.51 +/- 0.07 to 0.27 +/- 0.02 mumol min-1 g-1 dry wt).
      Upon rewarming glucose and fatty acid oxidation rates returned to essentially the
      same values (0.12 +/- 0.02 and 0.45 +/- 0.04 mumol min-1 g-1 dry wt) as those
      observed under steady state normothermic conditions. The molar ratio between
      glucose and fatty acid oxidation was, however, significantly (P < 0.05) lower in
      hypothermic than in normothermic hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266804
TI  - The influence of afterload on uniformity of segment shortening in feline left
      ventricles. Importance of cross-fibre contraction.
AB  - Previous studies have shown that the combined increase of preload and afterload
      leads to a more uniform wall contraction. As our previous information with a
      stable afterloaded situation showed considerable increase of left ventricular end
      diastolic pressure, we have as yet no information of how afterload per se effects
      uniformity of segment shortening. We therefore analysed maximal systolic
      shortening of cross-oriented segments for three consecutive beats during abrupt
      elevation of afterload in 12 open-chest cats. Peak left ventricular systolic
      pressure increased during the three beats from 154 +/- 5 mmHg (mean +/- SEM) to
      167 +/- 5 mmHg and 186 +/- 5 mmHg. Left ventricular end-diastolic pressure
      remained unchanged. Maximal systolic shortening was reduced for both segments
      with increasing afterload, in longitudinal segment (LONG) from 7.6 +/- 1.1 to 6.1
      +/- 1.0% (P < 0.005), and more pronounced for circumferential segments (CIRC)
      from 12.2 +/- 0.7 to 8.3 +/- 0.9% (P < 0.0005). Uniformity of maximal systolic
      shortening, LONG/CIRC, increased from 0.63 +/- 0.08 in the first beat to 0.73 +/-
      0.10 and 0.82 +/- 0.12 in the following beats (P < 0.02). We conclude that
      uniformity of contraction for cross-oriented segments in the anterior left
      ventricular wall is increased during increased afterload. We propose that this
      can be explained by reduction of the effect of cross-fibre contraction with
      increasing afterload.

PMID- 8266805
TI  - Significance of increased atrial pressure on stroke volume during atrial
      fibrillation in anaesthetized pigs.
AB  - During atrial fibrillation synchronized atrial contraction is lost and cardiac
      output declines. Concomitantly, atrial pressure increases. The significance of
      the increase in atrial pressure on stroke volume was examined before and after
      blood volume expansion. Atrial fibrillation was induced by rapid atrial pacing in
      seven anaesthetized, open-chest pigs. The increase in right atrial pressure
      subsequently was counteracted by an appropriate constriction of the inferior vena
      cava. To avoid the confounding effect of a rapid and irregular heart rate,
      ventricular rate was kept constant by separate His bundle pacing after complete
      atrioventricular block. When atrial fibrillation was induced, right and left
      atrial pressure at the top of the v-wave increased both during normovolaemia and
      during hypervolaemia. Concomitantly, stroke volume declined. When the increase in
      atrial pressure was prevented during atrial fibrillation, stroke volume declined
      further: by 35 (21-50) and 9 (2-17)% (difference: P = 0.01), during normo- and
      hypervolaemia, respectively. Thus, the increase in atrial pressure counteracts
      the decline in stroke volume after induction of atrial fibrillation and thereby
      represents an important compensatory mechanism. This mechanism is more important
      with normal blood volume than during hypervolaemia.

PMID- 8266806
TI  - Effect of serotonin receptor blockade on endocrine and cardiovascular responses
      to head-up tilt in humans.
AB  - Effects of blockade of serotonin (5-HT) receptors on the integrated
      cardiovascular and endocrine adaptations during head-up tilt were investigated in
      normal men. In control experiments 50 degrees head-up tilt increased heart rate
      (HR), total peripheral resistance (TPR), plasma renin activity (PRA) and
      sympathetic activity (plasma noradrenaline; NA). A moderate increase in pituitary
      adrenal hormones (plasma ACTH, beta-END and cortisol) was observed. After a mean
      tilt time of 30 +/- 5 min (n = 20) presyncopal symptoms associated with decreases
      in HR, TPR and arterial pressure occurred. At this time pituitary hormones,
      cortisol, adrenomedullary (plasma adrenaline; A) as well as vagal activity
      (plasma pancreatic polypeptide) were markedly increased, whereas sympathetic
      activity (plasma NA) decreased. The 5-HT1+2 receptor antagonist methysergide did
      not significantly interfere with cardiovascular variables but attenuated the
      response of NA, prolactin (PRL), beta-endorphin (beta-END) and PRA (P < 0.02).
      The 5-HT2-receptor antagonist ketanserin reduced the tolerated tilt time (10 +/-
      4 vs. 32 +/- 2 min; P < 0.0003, n = 7) but had no significant effects on hormonal
      variables. The 5-HT3-receptor antagonist ondansetron abolished the
      adrenomedullary response to hypotension without affecting cardiovascular
      tolerance or the activity of the pituitary-adrenal axis. The results suggest that
      serotonergic mechanisms may be involved in the integrated cardiovascular and
      endocrine responses to central blood volume depletion in humans.

PMID- 8266807
TI  - Inducibility of NADP-specific isocitrate dehydrogenase with endurance training in
      skeletal muscle.
AB  - NADP(+)-specific isocitrate dehydrogenase (ICDH-NADP: EC 1 x 1 x 1 x 42) is
      primarily a mitochondrial matrix enzyme in both mammalian skeletal muscle and
      heart and has markedly higher activity levels than the NAD(+)-specific isozyme.
      To date, it is unknown whether ICDH-NADP activity is inducible with in vivo
      exercise training in locomotor or respiratory skeletal muscle. Therefore, the
      purpose of this investigation was to quantify alterations in ICDH-NADP activity
      in respiratory muscles (costal and crural diaphragm) and locomotor muscles
      (medial gastrocnemius, plantaris and soleus) following 8 weeks of treadmill
      endurance training. Ten of the animals had been assigned randomly to an exercise
      group (TR) and had completed 8 weeks of progressive (5 days week-1: 45 min day-1)
      treadmill endurance training while the remaining 10 animals comprised a sedentary
      control (C). Mean ICDH-NADP activities in Tr were significantly higher (P < 0.05)
      when compared with C in the medial gastrocnemius (61.3%), plantaris (42.9%)
      soleus (21.4%). Mean costal diaphragm ICDH-NADP activity noted in trained animals
      when compared to the sedentary control group was not significantly higher (10.8%
      greater for TR; P = 0.14). No mean differences (P = 0.58) were noted in the
      crural diaphragm. The results indicate that ICDH-NADP is inducible with endurance
      training in locomotor skeletal muscle. A coefficient of determination of 0.624
      (i.e. 62.4% of the variance could be explained) for ICDH-NADP was calculated,
      with the oxidative enzyme marker succinate dehydrogenase (P < 0.05) indicating a
      positive, moderate relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266808
TI  - Distribution of recurrent inhibition in the human upper limb.
AB  - The distribution of homonymous and heteronymous recurrent inhibition among the
      motor nuclei innervating the main muscles of the human upper limb has been
      investigated in 25 healthy subjects. Homonymous recurrent inhibition was studied
      with a specially designed electrophysiological method with paired H-reflexes,
      previously described by Bussel & Pierrot-Deseilligny (1977), combined with a
      pharmacological study using a cholinergic agonist, the L-acetylcarnitine (Rossi &
      Mazzocchio 1991). These methods were used to investigate the Flexor Carpi
      Radialis (FCR), Extensor Carpi Radialis (ECR), Opponens Pollicis (OP) and
      Abductor Digiti Minimi (ADM) motor nuclei. In the Deltoid, Triceps, Flexor Carpi
      Ulnaris (FCU) and Extensor Carpi Ulnaris (ECU) motor nuclei in which it was
      impossible to evoke clearly distinguishable H-reflexes, homonymous recurrent
      inhibition was studied with the PSTH technique: homonymous recurrent inhibition
      was found in Deltoid, Triceps, FCR, FCU, ECR, ECU motor nuclei but not in OP and
      ADM motor nuclei. Heteronymous recurrent inhibition was studied with the PSTH
      technique in the Deltoid, Biceps, Triceps, FCR, ECR, FCU, ECU, Flexor Digitorum
      Communis (FDC), Extensor Digitorum Communis (EDC) motor nuclei as well as those
      innervating the intrinsic muscles of the hand. The following results were
      obtained: (1) motor neurones innervating muscles acting at digits do not receive
      any heteronymous recurrent inhibition; (2) motor neurones innervating muscles
      acting at the wrist give recurrent inhibition to motor nuclei of proximal muscles
      but do not receive any recurrent projections from the latter; and (3) motor
      neurones innervating proximal muscles (acting at shoulder or elbow) are
      interconnected by recurrent inhibition and receive heteronymous recurrent
      projections from some wrist muscles but not from intrinsic hand muscles.

PMID- 8266809
TI  - The antinociceptive effect of non-noxious sensory stimulation is mediated partly
      through oxytocinergic mechanisms.
AB  - The objective of the present study was to investigate whether oxytocinergic
      mechanisms may contribute to the antinociceptive effect of non-noxious, sensory
      stimulation. To test this hypothesis, oxytocin levels in plasma and cerebrospinal
      fluid (CSF) were measured in control rats as well as in rats exposed for 30 min
      to electro-acupuncture (2 Hz), thermal stimulation (40 degrees C) or vibration
      (100 Hz). All modes of stimulation induced significant elevations of oxytocin
      levels in plasma and/or in CSF, 30 or 90 min after the end of stimulation.
      Secondly, the antinociceptive effects of these treatments were investigated in
      the tail-flick test with and without prior administration of the oxytocin
      antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin (1 mg kg-1 i.p.). All
      three modes of stimulation caused a significant delay of the tail-flick latency
      to the same degree as that caused by injection of oxytocin 1 mg kg-1 i.p.
      (electro-acupuncture P < 0.01, thermal stimulation and vibration P < 0.05). In
      all cases, the delay was reversed by administration of the oxytocin antagonist (1
      mg kg-1 i.p.). These findings suggest that analgesic effects induced by non
      noxious sensory stimulation may, in part, be mediated through activation of
      oxytocinergic mechanisms.

PMID- 8266810
TI  - Control of shivering and heart rate in incubating bantam hens upon sudden
      exposure to cold eggs.
AB  - To distinguish shivering released by cooling of the brood patch from shivering
      released by low core temperature, incubating bantam hens were exposed to water
      perfused eggs. Responses to a period of egg cooling were compared to the recovery
      period after egg temperature had been returned to 40 degrees C, but cloacal
      temperature (Tb) still was low. At an ambient temperature (Ta) of 23 degrees C
      and exposure of the hens to between two and eight eggs cooled to 10-35 degrees C
      (series 1), electromyographic (EMG) activity of musculus iliotibialis increased
      rapidly with an occasional overshoot, and was higher during egg cooling than
      during recovery. This hysteresis in EMG activity and Tb was weakly correlated to
      egg temperature and clutch size. Heart rate (HR) showed an almost parallel
      increased to shivering except that a maximum HR was reached at high shivering
      intensities. These responses were also present at a Ta of 37 degrees C when the
      hens were slightly hyperthermic before exposure to eight eggs at 20 degrees C
      (Series 2). At the highest starting Tbs EMG activity increased linearly after a
      drop in Tb. Shivering in m. pectoralis showed a lower threshold Tb and lower
      activity than m. iliotibialis during egg cooling, and immediately ceased at the
      end of egg cooling. Total body thermosensitivity estimated from the recovery
      periods at low and high Ta was -9.7 and -6.4 W kg-1 degrees C-1, respectively. It
      is concluded that shivering in incubating birds warming cold eggs probably is
      stimulated both by peripheral and central thermoreceptors. The peripheral
      component shows phasic properties typical for skin receptors.

PMID- 8266811
TI  - In-vivo glucose uptake and glucose transporter proteins GLUT1 and GLUT3 in brain
      tissue from streptozotocin-diabetic rats.
AB  - The effects of streptozotocin-induced diabetes (13 weeks) on the in-vivo glucose
      uptake and on the protein levels of glucose transporters in rat brain were
      studied and compared with those in cardiac muscle. Diabetes reduced the uptake of
      2-[3H]deoxyglucose into lobus frontalis by 70%. However, uptake rates corrected
      for the 4-fold increase in serum glucose (glucose metabolic index, GMI) were
      essentially unaltered. The levels of glucose transporter proteins GLUT1 and GLUT3
      in crude membranes from brain as assessed by immunoblotting were unaffected by
      diabetes, whereas GMI and levels of glucose transporters GLUT1 and GLUT4 in heart
      were reduced by 80 and 65%, respectively. Thus, glucose uptake and levels of
      glucose transporters in brain, unlike that in insulin sensitive tissues, are
      normal in long-term hypo-insulinaemia.

PMID- 8266812
TI  - Exogenous arachidonic acid inactivates protein kinase C in mouse pancreatic
      islets.
AB  - The effect of arachidonic acid on protein kinase C activity and insulin secretion
      in mouse islets was investigated. Arachidonic acid stimulated protein kinase C
      activity in islet cytosol and membrane fractions by substituting for
      phosphatidylserine. Stimulation by arachidonic acid was dependent on either Ca2+
      or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, was potentiated by the
      combined addition of Ca(2+) + 12-O-tetradecanoylphorbol 13-acetate, and did not
      further increase protein kinase C activity in the presence of saturating
      concentrations of phosphatidylserine. Arachidonic acid stimulation of protein
      kinase C was prevented by binding of arachidonic acid to albumin. In the absence
      of extracellular Ca2+, exogenous arachidonic acid stimulated insulin secretion.
      Arachidonic acid-induced insulin secretion was not potentiated by 12-O
      tetradecanoylphorbol 13-acetate and was not prevented by the protein kinase C
      inhibitor staurosporine, suggesting that arachidonic acid-induced insulin
      secretion may occur independently of protein kinase C activation. Arachidonic
      acid-induced insulin secretion in Ca(2+)-free medium was on the other hand
      potentiated by addition of extracellular Ca2+. Stimulation of insulin secretion
      by exogenous arachidonic acid was associated with inactivation of protein kinase
      C. Inactivation of protein kinase C was also observed in islet homogenate after
      pre-incubation with arachidonic acid. Arachidonic acid-induced protein kinase C
      inactivation in islet homogenate was prevented by albumin or MgATP. Inactivation
      by arachidonic acid in intact islets was, however, not produced during enzyme
      isolation and was not prevented by inclusion of albumin or MgATP during
      preparation of protein kinase C extracts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266813
TI  - Hyaluronan turnover in the rat small intestine.
AB  - The main metabolic pathway for the interstitial matrix component hyaluronan seems
      to be via lymph. Present estimates of turnover of intestinal hyaluronan are based
      on isolated organs and/or experiments in anaesthesia over a few hours. In this
      study lymph was sampled from the main mesenteric lymphatic for 24 h in awake,
      restrained rats. The tissue content of hyaluronan averaged 28 micrograms g-1 in
      the duodenum/jejunum and 124 micrograms g-1 in the colon. Based on tissue content
      and lymphatic output, the turnover rate of hyaluronan in the small intestine was
      estimated at approximately 50%. In another experimental group anaesthetized rats
      were fed either phosphate buffer or triolein in buffer via a gastric tube. Lymph
      flow increased with fluid absorption from the gut and hyaluronan output in lymph
      was elevated correspondingly. However, no effect of acute fat administration on
      hyaluronan concentration or lymph flow could be demonstrated.

PMID- 8266814
TI  - Muscle fibre type changes with sprint training: effect of training pattern.

PMID- 8266815
TI  - Prevention of resistance to IFN-alpha antiproliferative activity:
      characterization of the effect of IFN-gamma and substitution for IFN-gamma by
      tumor necrosis factor.
AB  - Non-genetic resistance to the antiproliferative effects of interferon-alpha (IFN
      alpha) develops in murine and human melanoma cells within 2-4 days of exposure of
      the cells to IFN-alpha. Simultaneous treatment of murine B16 melanoma cells with
      MuIFN-gamma and MuIFN-alpha prevents the development of resistance. In this
      study, the ability of MuIFN-gamma pretreatment to prevent the development of
      resistance was assessed for varying concentrations of MuIFN-gamma and for varying
      lengths of time of pretreatment. Pretreatment of the cells for 48 h with MuIFN
      gamma using concentrations as low as 5 U/ml prevents the subsequent development
      of resistance when the cells are cloned in the presence of MuIFN-alpha. Higher
      concentrations of MuIFN-gamma are more effective in preventing the development of
      resistance. In addition, short MuIFN-gamma pretreatment times, such as 2-4 h,
      appeared to be most effective in preventing the development of resistance. In
      order to determine the mechanism for this biological effect, various second
      messenger perturbing chemical agents and several other biological agents were
      screened for ability to prevent the development of resistance. Neither
      interleukin-2 (IL-2), epidermal growth factor (EGF), nor any of the chemical
      agents examined could prevent the development of resistance, nor did they alter
      the ability of MuIFN-gamma to prevent the development of resistance. Tumor
      necrosis factor (TNF), however, was able to substitute for MuIFN-gamma in
      preventing the development of resistance, using concentrations of 125 ng/ml and
      higher.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266816
TI  - Long term therapy with recombinant interferon alpha 2 b in patients with chronic
      hepatitis C: effects on thyroid function and autoantibodies.
AB  - Twelve anti HCV-positive patients (8 males and 4 females; 37-62 yrs) suffering
      from chronic active viral hepatitis have been evaluated in order to determine
      serum thyroid hormones and autoantibody pattern during recombinant interferon
      alpha 2b (IFN-alpha 2b) therapy. The interferon was given subcutaneously three
      times per week for six months in a single standard dose of 3 MU. For a further
      six months 5 patients (Group A) received the same interferon at 1MU dose three
      times per week and 7 (Group B) had no treatment. Serum T3, T4, FT4, TBG, TSH,
      TGAb and TMAb were determined on serum collected before the start of the
      treatment and every month for 12 months thereafter. Except for one case, in which
      a transient reduction in thyroid hormone values and an increase in TSH levels was
      recorded, none of the patients studied showed a significant variation of serum
      hormonal parameters or appearance of pathological TGAb and/or TMAb levels. The
      data indicate that the administration of recombinant IFN-alpha 2b to HCV positive
      chronic active hepatitis patients at the dose and schedule employed in the
      present study may result in a reduction in the incidence of thyroid dysfunction
      related to the IFN therapy.

PMID- 8266817
TI  - High molecular weight hepatotrophic factors released in serum-free medium by the
      cultured embryo rat fibroblastic cell line FRL.
AB  - Two hepatotrophic protein factors (HTF) were partially purified from the serum
      free conditioned medium of the embryo rat fibroblastic cell line FRL. HTF induced
      cell adherence to the culture plate, promoted life maintenance, scattering and
      enhanced 3H-Thymidine uptake into DNA and cell proliferation in two sensitive
      murine non-transformed, epithelial hepatocytic cell lines (C6 and C2.8). In this
      bio-assay, cells were plated at low density in Dulbecco's Modified Eagle's
      Medium, in the absence of serum and other exogenous growth factors. HTF did not
      synergize with epidermal growth factor. Biological activity was associated to two
      major acidic proteins: a non-heparin-binding protein (M(r) approximately 70 kDa,
      pI 4.6-4.5) and a heparin-binding protein (M(r) approximately 200 KDa, pI 4.3
      4.1).

PMID- 8266818
TI  - Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced
      cancer patients with abnormally high blood levels of tumor necrosis factor-alpha.
AB  - TNF, in addition to its antitumor activity, would play an important role in the
      pathogenesis of cancer-related severe complications, including ARDS and DIC.
      Therefore, the modulation of TNF secretion could be important in the supportive
      care of advanced cancer patients. At present, PTX is the only drug which has been
      proven to be able to inhibit in vitro the release of TNF. The present study was
      performed to evaluate the effect of PTX on TNF blood concentrations in
      disseminated cancer patients with abnormally high TNF values. The study included
      14 cancer patients, with initial or conclamate signs of ARDS (n = 8) or DIC (n =
      6). PTX was given intravenously at a dose of 300 mg/day for 7 days. Mean serum
      levels of TNF significantly decreased in response to PTX therapy, and they
      returned to normal range in 5/14 patients. These preliminary data would suggest
      that PTX may be considered as a biological response modifier, capable of
      inhibiting TNF secretion in humans, with a following potential use in the
      treatment of cancer-related severe complications.

PMID- 8266819
TI  - Importance of bone resorption in the determination of bone density in women more
      than 10 years past the menopause.
AB  - There is general agreement that bone density falls with age and is higher in
      heavy people than light people. We have studied a variety of potential correlates
      of vertebral, ankle, and hip bone density to evaluate other potential influences
      on the skeleton. We recruited 196 healthy women who were more than 10 years past
      the menopause and collected a diet and activity record, a 24 h urine, and a
      fasting blood and urine specimen. These blood and urine samples were analyzed for
      factors related to calcium homeostasis. We then measured bone density at lumbar
      vertebrae 1-4 and the hip and the ankle bone density of the nondominant leg.
      Correlations between vertebral, hip, and ankle bone density and other measured
      variables were explored using the statistical package SPSS PC. At the vertebral
      site, in addition to correlations with age and body mass index (BMI), a negative
      correlation with a measure of bone resorption, the hydroxyproline creatinine
      ratio (OHPCR), was noted. At the ankle site, in addition to correlation with age,
      BMI, and OHPCR, a positive correlation with activity and a negative correlation
      with serum calcitriol were noted. At the hip site, as well as age, BMI, and
      OHPCR, significant correlations with GFR and dietary calcium intake were noted.
      These data suggest that even in women 10 years past the menopause bone resorption
      has a significant effect on bone density, that renal function may account for
      some of the variance in bone density at the hip, and that activity effects are
      more marked at sites of greater loading, namely the ankle.

PMID- 8266820
TI  - Intestinal malabsorption of 45calcium in young Gy mice, a second model for X
      linked hypophosphatemia.
AB  - X-linked hypophosphatemia, a common metabolic bone disease in humans and mice
      (the Hyp and Gy mutations), is characterized by decreased plasma phosphate,
      decreased renal tubular reabsorption of phosphate, rickets, and osteomalacia. The
      question of whether intestinal malabsorption of calcium contributes to the bone
      disease is controversial. Intestinal absorption of 45Ca was studied in three
      different mouse colonies: Gy on B6C3H background, Hyp on B6C3H background, and
      Hyp on C57BL/6J background, all at 4 weeks of age. The duodenum was isolated by
      sutures, and 45Ca in a 150 mM NaCl and 2 mM CaCl2 solution at pH 7.2 was injected
      into the lumen. Absorption was measured by the amount of 45Ca remaining in the
      lumen and by the plasma isotope level. The Gy and Hyp mice of both sexes
      significantly malabsorbed 45Ca at 4 weeks of age compared to normal littermates.
      Following the 4 week study, intestinal absorption was measured at 2, 7-8, and 12
      weeks of age in normal and Gy mice on the B6C3H background. At 2 and 7-8 weeks of
      age, the Gy males significantly malabsorbed 45Ca compared to their normal
      littermates. Serum 1,25-dihydroxyvitamin D was not significantly altered in Gy
      males at 4 weeks of age. This suggests the possibility of resistance of the
      intestine to stimulation. Malabsorption of calcium in young Gy and Hyp mice may
      exacerbate the low mineralization in their rachitic bone disease.

PMID- 8266821
TI  - Effects of bone-seeking hormones on DNA synthesis, cyclic AMP level, and alkaline
      phosphatase activity in cultured cells from human posterior longitudinal ligament
      of the spine.
AB  - In a study of the osteogenesis capability of the human posterior longitudinal
      ligament of the spine, ligament cells were isolated and cultured. The effect of
      bone-seeking hormones, such as parathyroid hormone (PTH), calcitonin (CT),
      prostaglandin E2 (PGE2), and 1,25-dihydroxycholecalciferol [1,25-(OH)2D3], on the
      ligament cells was investigated with respect to DNA synthesis, adenosine-3',5'
      cyclic monophosphate (cAMP) levels, alkaline phosphatase (ALP) activity, and acid
      phosphatase (ACP) activity. Cell lines obtained from nonossified sites in
      patients with ossification of the posterior longitudinal ligament of the spine
      (OPLL) were found to have several different phenotypic characteristics for
      osteoblasts: high ALP activity, PTH- and PGE2-stimulated increases in cAMP, and
      responses to both CT and 1,25-(OH)2D3. It is clear that proliferation and
      differentiation in such ligament cells are controlled by various types of bone
      seeking hormones, and it was suggested that many cells with osteoblast-like
      characteristics are present. These results are considered important with respect
      to the etiology of OPLL, and an experimental system using cultured ligament cells
      appears to be useful in research on OPLL.

PMID- 8266822
TI  - Stimulatory effect of TGF-beta on anionic glycoconjugate synthesis by rat
      calvarial cells: specificity, uncoupling of cell density dependence, and
      modulation by chondroitin sulfate.
AB  - Anchorage-dependent cultures of a population of cells derived from the outer part
      of the rat calvaria demonstrated decreased net accumulation of radiolabeled
      chondroitin sulfate (CS) and hyaluronic acid (HA) per cell as the cell density of
      the cultures increased. The addition of TGF-beta 1 resulted in large stimulations
      of the net CS, but not of the net HA, accumulating in the medium at all cell
      densities and an abolition of the density-dependent effect. These effects were
      largely due to increases in newly synthesized CS appearing in the medium.
      Supplementation of the culture media with CS had complex but relatively small
      effects on the stimulation of the net accumulation of radiolabeled medium CS by
      TGF-beta 1. The addition of TGF-beta 1 also resulted in a biphasic effect on cell
      growth that depended on the plating density, but cell growth differences could
      not account for the marked stimulation of CS synthesis by TGF-beta 1. Experiments
      with cycloheximide and beta-xyloside and isolation of the intact anionic
      glycoconjugates (AG) indicated that although synthesis of core protein was the
      limiting factor in CS synthesis, TGF-beta 1 stimulated the synthesis of CS chain
      when sufficient beta-xyloside acceptor was available. The overall results suggest
      that, in this cell system, the action of TGF-beta 1 on the synthesis of the major
      extracellular AGs is characterized by a relatively specific upregulation of CS
      proteoglycan (PG) synthesis and an uncoupling of the inhibitory effect of high
      cell density on CS PG synthesis.

PMID- 8266824
TI  - Streaming potentials in healing, remodeling, and intact cortical bone.
AB  - Electrical fields have been implicated in accelerated bone healing and as a
      transduction mechanism for mechanically driven bone remodeling. Applied
      mechanical or electrical stimulation of bone remodeling suggests that this
      depends on the magnitude, frequency, and duration of the stimulus. The magnitude
      of endogenous electrical fields, manifest by streaming potentials (SPs) across
      canine cortical bone, were measured as a function of bending frequency in vivo
      and then in vitro at healing drill holes and at remodeling (ipsilateral) and
      normal, intact (contralateral) control sites in canine tibia. SP magnitudes
      normalized to periosteal strain were smaller for drill holes at 2 and 4 weeks
      postsurgery relative to either remodeling (P < 0.05 at 10 Hz) or normal intact (P
      < 0.001 at 10 Hz) controls both in vivo and in vitro. SPs of 12 week drill holes
      were similar to SPs of remodeling controls and tended to be smaller than SPs of
      normal intact controls. Mean SP normalized to bone impedance was approximately
      the same for all sites, suggesting that the smaller SPs during healing and
      remodeling relate to smaller bone impedance and/or larger porosity. SP as a
      function of bending frequency for normal sites was similar to that observed
      previously. SP versus frequency for drill holes and remodeling controls was more
      variable, probably because of variations in bone microstructure, and displayed a
      higher frequency content. The observed differences in SP magnitude and frequency
      response to loading associated with stages of healing indicate that endogenous
      electrical fields do indeed respond to the structural changes in healing and
      remodeling and are therefore capable of providing structural feedback information
      for the repair and remodeling process.

PMID- 8266823
TI  - Evaluation of the skeletal effects of combined mild dietary calcium restriction
      and ovariectomy in Sinclair S-1 minipigs: a pilot study.
AB  - A pilot study was conducted to investigate the combined effects of ovariectomy
      (OVX) with preceding and concomitant mild dietary calcium restriction on the
      minipig skeleton. Minipigs 4 months old were fed diets containing 0.9, 0.75, or
      0.5% calcium (Ca). At 10 months, the 0.75 and 0.5% pigs were OVX and the 0.9%
      were either sham operated or OVX. All pigs were maintained on their respective
      diets for an additional 6 months. Excised lumbar vertebrae and long bones were
      evaluated by densitometry and histomorphometry, and vertebral cancellous bone
      samples were tested biomechanically. In pigs fed the 0.9% Ca diet, OVX alone
      effected decreases of 6% in vertebral bone mineral density (BMD), 15% in
      trabecular bone volume (BV/TV), and 13% in trabecular number (Tb.N), an increase
      of 15% in trabecular separation (Tb.Sp), and a nonsignificant increase (p <
      0.056) in vertebral cancellous final erosion depth (F.E.De) compared with the
      0.9% Ca sham-operated group. Decreasing dietary Ca to 0.5% in combination with
      OVX effected an 8% reduction in vertebral BMD that was not associated with any
      significant alterations in parameters of vertebral cancellous bone microstructure
      or remodeling compared with the 0.9% Ca sham-operated pigs. Increases in serum
      PTH noted in the 0.5% Ca OVX group were generally paralleled by increases in
      calcitriol. In OVX pigs fed a diet containing 0.75% Ca, a 10% reduction in
      vertebral BMD was observed. This was associated with significant increases in
      F.E.De and vertebral marrow star volume (Ma.St.V) compared with the 0.9% Ca sham
      operated pigs and the other OVX groups. In addition, Tb.Sp was increased and Tb.N
      decreased compared with the 0.9% Ca sham-operated pigs. Increases in serum PTH in
      this group were not accompanied by increases in calcitriol. Midradial and
      midfemoral BMD values were reduced in the 0.75 and 0.5% Ca OVX groups compared
      with the 0.9% Ca sham-operated pigs. Histomorphometric analyses of cortical bone
      suggested the reduction in cortical bone mass in the 0.75% Ca OVX group may have
      been largely due to net loss on the endocortical surface versus possible failure
      to accrue bone in the 0.5% Ca OVX group. Ash density and biomechanical parameters
      for vertebral cancellous bone decreased progressively in the 0.9% sham-operated,
      0.9% Ca OVX, and 0.75% Ca OVX groups and then increased in the 0.5% Ca OVX group.
      After normalization for bone mass (ash), mechanical changes were still apparent,
      particularly for the 0.75% Ca OVX group compared with other OVX groups,
      reflecting that structural changes had taken place in the trabecular
      network.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8266825
TI  - Effects of interleukin-4 on the formation of macrophages and osteoclast-like
      cells.
AB  - The lymphokine interleukin-4 (IL-4) is an important lymphocyte growth factor, and
      it also has a modulatory role on hematopoiesis. It was recently reported that IL
      4 has an inhibitory effect on bone resorption in vitro, but the underlying
      mechanisms are not well known. We studied its effects on the formation of
      osteoclast-like cells in mouse bone marrow cultures and in cocultures of spleen
      cells and stromal cells. The addition of recombinant mouse IL-4 (0.01-10 ng/ml)
      induced a marked dose-dependent inhibition on the formation of TRAP-positive
      multinucleated cells (MNC) in bone marrow cultures. The effect was blocked by
      anti-IL-4 antibodies and was not related to a decreased production of IL-6. The
      inhibitory effect required the presence of IL-4 during the second half of the
      culture period. Time course experiments showed that IL-4 impaired the formation
      of osteoclast-like cells rather than inducing the disappearance of previously
      formed cells. This inhibitory effect was associated with increased numbers of
      esterase-positive cells. Moderately high doses of IL-4 (1-10 ng/ml) also induced
      the formation of abundant macrophage polykaryons that did not form resorption
      pits. IL-4 had a similar inhibitory effect on the formation of osteoclast-like
      cells in cocultures of mouse spleen cells and stromal cells. Our results suggest
      that IL-4 acts on uncommitted macrophage-osteoclast precursors, inducing a
      preferential differentiation toward the macrophage lineage and thus decreasing
      the formation of osteoclast-like cells.

PMID- 8266826
TI  - A new bisphosphonate, BM 21.0955, prevents bone loss associated with cessation of
      ovarian function in experimental dogs.
AB  - We previously found that bone loss occurs as soon as 1 month after
      ovariohysterectomy (OHX) in beagle dogs. Indirect evidence pointed to an early
      dramatic increase in bone resorption. To verify this hypothesis and evaluate the
      effects of a newly developed bisphosphonate, BM 21.0955 (Boehringer Mannheim), 36
      beagle dogs were subjected to OHX and 12 dogs were sham operated (Sham). OHX dogs
      were divided into six groups (n = 6 each) and received subcutaneous injections of
      vehicle or BM 21.0955 at various doses (0.1, 0.3, 1, 10, and 100
      micrograms/kg/day) for 1 month. Sham dogs were given vehicle (n = 6) or BM
      21.0955 (1 microgram/kg/day, n = 6). Iliac crest biopsies and blood drawings were
      done at baseline and at month 1. OHX dogs given vehicle exhibited a decrease in
      cancellous bone volume associated with an increase in erosion depth and a
      decrease in serum levels of 1,25-dihydroxyvitamin D. BM 21.0955 prevented the
      bone loss at a dose > or = 1 microgram/kg and the increase in erosion depth and
      the decrease in serum levels of 1,25-(OH)2D at a dose > or = 0.3 microgram/kg. No
      osteomalacia was observed at any dose of BM 21.0955. Bone turnover was reduced
      only when BM 21.0955 was administered at doses of 10 or 100 micrograms/kg. There
      were no changes in body weight or serum levels of calcium, phosphorus,
      creatinine, parathyroid hormone, or osteocalcin in all groups. The increase in
      erosion depth in OHX dogs given vehicle proves that the early rapid bone loss
      after cessation of ovarian function is related to an increase in osteoclastic
      activity. The antiosteoclastic activity of BM 21.0955 at a dose > or = 1
      microgram/kg prevents this increase and preserves bone volume. The absence of any
      signs of osteomalacia at any dose confers a relatively wide therapeutic margin to
      BM 21.0955. BM 21.0955 at a dose > or = 10 micrograms/kg also acts as an
      inhibitor of bone turnover. This is not observed at a dose of 1 microgram/kg, at
      least after 1 month of administration.

PMID- 8266827
TI  - Differential effects of fluoride during initiation and progression of
      mineralization of osteoid nodules formed in vitro.
AB  - Osteoid nodules form in cultures of fetal rat calvarial (RC) cells grown in
      medium containing 10% FBS and 50 micrograms/ml of ascorbic acid. When 10 mM beta
      glycerophosphate (beta-GP) is added, osteoid nodules mineralize in two phases: an
      initiation phase, which is dependent upon alkaline phosphatase activity for
      conversion of beta-GP to P(i), and a progression phase that proceeds
      independently of alkaline phosphatase activity and does not require exogenous
      phosphate. We have now used this system to investigate the effects of fluoride (F
      ) on mineralization. In cultures in which osteoid was formed and mineralization
      initiated in the presence of F-, a dose-dependent inhibition of the initiation of
      mineralization occurred over a concentration range of 25-500 microM F- (p < 0.001
      in all cases). The initiation of mineralization was not inhibited if F- was
      removed from the cultures at the time when mineralization was initiated with beta
      GP. In osteoid nodules grown in the absence of F-, addition of F- resulted in a
      dose-dependent inhibition of the initiation of mineralization, with significant
      decreases in 45Ca uptake occurring at F- concentrations of 3 microM (p < 0.01)
      and higher. However, if F- was added to cultures after mineralization was
      initiated in the absence of F-, a stimulation of 45Ca uptake was observed at F-
      concentrations of 250 microM and above (p < 0.001). F- (1-1000 microM) did not
      affect the conversion of beta-GP to P(i) or alkaline phosphatase activity in the
      cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266828
TI  - Cell signaling and estrogens in female rat osteoblasts: a possible involvement of
      unconventional nonnuclear receptors.
AB  - Estrogen deficiency is associated with bone loss, and estrogen replacement is an
      effective treatment of this osteoporotic process. This study examines the early
      (5-120 s) effects of 17 beta-estradiol on the intracellular calcium and
      phospholipid metabolism in confluent female rat osteoblasts. The cytosolic free
      Ca2+ concentration ([Ca2+]i) was determined using fura-2/AM as Ca2+ probe. Cells
      were labeled with myo-[2-3H]inositol or [14C]arachidonic acid for inositol or
      lipid determination. Inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG)
      production were determined by either mass measurement or anion-exchange
      chromatography or by thin-layer chromatography, respectively. 17 beta-Estradiol
      (1 pM to 1 nM) increased [Ca2+]i in a biphasic manner within 10 s via Ca2+ influx
      from the extracellular milieu, as shown by the effects of the calcium chelator
      EGTA and the Ca2+ channel blockers nifedipine and verapamil, and via Ca2+
      mobilization from the endoplasmic reticulum (ER), as shown by the effects of
      thapsigargin. 17 beta-Estradiol (1 pM to 1 nM) induced a biphasic and concomitant
      increase in IP3 and DAG formation. Estradiol immobilized on bovine serum albumin
      (BSA) [E-(O-carboxymethyl)oxime BSA] and its derivative (O-carboxymethyl)oxime
      rapidly increased ([Ca2+]i, IP3, and DAG and were full agonists, although they
      were less potent than the free estradiol. They had the same action time course
      and acted via Ca2+ influx and Ca2+ mobilization from ER. Tamoxifen, a potent
      inhibitor of genomic steroid responses, did not block the rapid increase in Ca2+,
      IP3, and DAG induced by estradiol. Finally, inhibitor of phospholipase C
      (neomycin) and pertussis toxin abolished the effects of 17 beta-estradiol on IP3
      and DAG formation. These results suggest that female rat osteoblasts bear non
      genomic unconventional cell surface receptors for estradiol, belonging to the
      class of the membrane receptors coupled to a phospholipase C via a pertussis
      toxin-sensitive G protein.

PMID- 8266829
TI  - Altered cartilage phenotype expressed during intramembranous bone formation.
AB  - The sequential phenotypic expression occurring during intramembranous bone
      formation was investigated using the tooth extraction socket created in rat
      alveolar bone in vivo. The differential expression of bone extracellular matrix
      genes, such as collagen I and osteocalcin, was confirmed by RNA transfer blot
      analysis and in situ hybridization during the active healing period of the bony
      socket. To clarify the possible involvement of the chondrogenic phenotype during
      the process of intramembranous bone formation, the expression of cartilage
      collagen II and IX was further examined in this model. It was found that both
      alpha 1(II) and alpha 1(IX) mRNAs were present, but the alpha 1(IX) mRNA was a
      transcript from the downstream start site/promoter, which is a different site in
      the alpha 1(IX) gene from that used in hyaline cartilage. In situ hybridization
      indicated that the alpha 1(IX) message was expressed by cells associated with
      bone matrix in the early formation stage. This finding led to the investigation
      of type IX collagen expression by osteogenic cells isolated from newborn rat
      calvariae, in which only the truncated form of alpha 1(IX) mRNA was indicated by
      RNA transfer analysis. The expression of collagen II and a truncated form of
      collagen IX may represent an early phenotypic feature of osteoblast
      differentiation.

PMID- 8266830
TI  - Interrelationships between densitometric, geometric, and mechanical properties of
      rat femora: inferences concerning mechanical regulation of bone modeling.
AB  - A compensation for differences in bone material quality by bone geometric
      properties in femora from two different strains of rats was previously shown by
      us. A feedback mechanism controlling the mechanical properties of the integrated
      bones was then proposed, in accordance with Frost's mechanostat theory. Evidence
      of such a system is now offered by the finding of a negative correlation between
      the modeling-dependent cross-sectional architecture (moment of inertia) and the
      mineral-dependent stiffness (elastic modulus) of bone material in the femoral
      diaphyses of 45 normal Wistar rats of different sexes, ages, and sizes. The
      strength and stiffness of the integrated diaphyses were found to depend on both
      cross-sectional inertia and body weight, not on bone mineral density. These
      findings are interpreted as supporting the hypothesis that the architectural
      efficiency of diaphyseal cross-sectional design resulting from the spatial
      orientation of bone modeling during growth is optimized as a function of the body
      weight-dependent bone strain history, within the constraints imposed by bone
      stiffness. Results suggest a modulating role of biomass, related to the system
      set point determination, and explain the usually observed lack of a direct
      correlation between mineral density and strength or stiffness of long bones in
      studies of geometrically inhomogeneous populations.

PMID- 8266831
TI  - Human 25-hydroxyvitamin D 24-hydroxylase cytochrome P450 subunit maps to a
      different chromosomal location than that of pseudovitamin D-deficient rickets.
AB  - We have cloned part of the human 25-OHD 24-hydroxylase cytochrome P450 (P450cc24)
      cDNA. The characterized sequence consists of 776 bp of the coding and 720 bp of
      the 3'-untranslated region interrupted by an intron. In the coding region we
      found 79.8% similarity in DNA and 87.5% in deduced amino acid sequences between
      human and rat, with no similarity in the 3'-untranslated region. By Southern blot
      hybridization of DNA from human-hamster somatic cell hybrids and by in situ
      immunofluorescence hybridization, we mapped P450cc24 to human chromosome 20q13.1.
      This location of P450cc24 is different from that of pseudovitamin D-deficient
      rickets (PDDR), previously assigned to chromosome 12q14 by linkage analysis, thus
      excluding it as a target of the PDDR mutation. Since it is likely that PDDR is
      caused by a mutation in the 25-OHD 1 alpha-hydroxylase P450 subunit (P450cc1
      alpha) our results do not support the hypothesis that the two cytochromes are
      encoded by a single gene.

PMID- 8266832
TI  - Characterization of radioiodinated recombinant human TGF-beta 1 binding to bone
      matrix within rabbit skull defects.
AB  - Bone healing is regulated in part by the local production of TGF-beta 1 and other
      growth factors produced by cells at the site of injury. The single application of
      recombinant human TGF-beta 1 (rhTGF-beta 1) to calvarial defects in rabbits
      induces an accelerated recruitment and proliferation of osteoblasts within 3
      days. This ultimately results in the formation of new bone and the complete
      closure of the defect within 28 days. The persistence and localization of
      [125I]rhTGF-beta 1 within an osseous defect was investigated after applying a
      single dose of [125I]rhTGF-beta 1 formulated in a 3% methylcellulose vehicle.
      Normal bone encompassing the defect site, the periosteum, and the gel film
      covering the dura were harvested at 0, 4, 8, and 24 h and 3, 7, and 16 days after
      [125I]rhTGF-beta 1 application. The defect site-associated radioactivity was
      quantitated, visualized by autoradiography, and characterized by TCA
      precipitation and SDS-PAGE. Radioactivity was observed in autoradiographs of
      gross specimens, histologic sections of the bone matrix, and periosteal tissue
      surrounding the defect. There was a time-dependent decrease in TCA-precipitable
      radioactivity; however, radioactivity was still associated with the bone matrix
      16 days after application of [125I]rhTGF-beta 1. SDS-PAGE and autoradiography of
      the radioactivity in homogenized bone and periosteal samples revealed a 25 kD
      band, suggesting that the radioactivity remaining at the defect site represented
      intact [125I]rhTGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266833
TI  - The ability of adolescents to predict future outcome. Part II: Therapeutic
      enhancement of predictive skills.
AB  - The assertion of autonomy, a developmental challenge of adolescence, helps
      predict the teenager's attitude toward pregnancy and parenthood. Significantly,
      the ability to predict the future relationship with the infant has direct
      implications for the achievement of an adaptive outcome. Indeed, the
      interpersonal outcome of the parent-infant relationship may be predicted by the
      adolescent's behaviors with her infant. A prospective orientation may offer an
      important vantage point for improving this relationship. For example, the ability
      to predict future outcome helps identify potential conflict, such as abuse. When
      applying a prospective approach during the prenatal period, the adolescent's past
      relationship with her own mother and her motivations for becoming a parent will
      be explored in order to predict the future dyadic relationship. For adolescents
      who are already parents, an assessment of the dyad's contemporaneous interaction
      may further predict future interpersonal exchange. Moreover, orienting the
      adolescent parent toward the future may identify areas of potential conflict, as
      well as foster more adaptive dyadic exchange.

PMID- 8266834
TI  - Adolescent affective aggression: an intervention model.
AB  - Affective aggression among adolescents is defined and described based upon
      primary research. A model of affective aggression is provided as a means of
      delineating the functional and observable components. Based upon these
      components, various interventions are provided as means of altering the
      aggression in adolescents.

PMID- 8266835
TI  - Death as portrayed to adolescents through top 40 rock and roll music.
AB  - Rock and roll music, an important influential communication source, provides
      adolescents with messages about death in our society. The first 37 years of Top
      40 rock songs (1955-1991) were examined, and songs that included a past death or
      an impending death were identified. The popularity of the songs, cause of death,
      gender of the deceased, and relationships among characters were determined.
      Analysis of song content was conducted, with specific emphasis on attitudes
      toward and means of coping with death. Results indicate that death songs comprise
      a disproportionately popular subset of Top 40 music, males dominate the
      obituaries, and grieving responses are restricted. Findings are discussed from a
      sociocultural perspective, with attention to their significance for adolescents.

PMID- 8266836
TI  - Occupational identity development, school performance, and social support in
      adolescence: findings of a Dutch study.
AB  - Three hundred adolescents completed a Dutch version of the Dellas Identity Status
      Inventory-Occupation (DISI-O). Reliability of the five subscales ranged from
      "sufficient" to "very good," and the four identity status classifications
      accommodated about 90% of the respondents. As expected, achievement and social
      support by friends in the educational setting stimulated development of
      occupational identity.

PMID- 8266837
TI  - Correlates of suicidal ideation in French-Canadian adolescents: personal
      variables, stress, and social support.
AB  - Two hundred seventy-two French-Canadian adolescent males and 286 females
      participated in a study of the relationship between suicidal ideation and
      selected personal variables, stress, and social support. Results of multivariate
      analyses indicated that suicidal ideation was positively related to depression,
      negative stress, and drug and alcohol use, and negatively related to self-esteem,
      satisfaction with social support, and school absenteeism.

PMID- 8266838
TI  - Risk factors associated with completed suicide in Latino adolescents.
AB  - This is the first study to explore potential psychosocial risk factors associated
      with completed suicide among Latino adolescents in the U.S. The sample (N = 14)
      included all the Latino adolescents aged 13 to 19 who committed suicide in Miami,
      Florida between January, 1988 and June, 1989. Data were derived from the medical
      examiner's records, family interviews, and a questionnaire completed by the
      school counselors of the victims and of an equal number of randomly selected
      Latino nonsuicidal matched-pair controls; t-tests were used to determine the
      significance of differences between victims and controls on the psychosocial risk
      variables explored. The victims had experienced significantly more school,
      personality, behavioral, and family stressors than had the controls. Implications
      for research and for suicide prevention are discussed.

PMID- 8266839
TI  - Risk factors for adolescent suicidal behavior: loss, insufficient familial
      support, and hopelessness.
AB  - Upon admission to an inpatient psychiatric facility, 20 adolescent serious
      suicide attempters and 20 nonattempters matched on depression scores were asked
      about their perceived hopelessness, social support, and loss preceding
      hospitalization. Attempters and nonattempters were similar in psychiatric status,
      gender, age, race, and socioeconomic status. Measures included Reynold's (1987)
      Suicidal Ideation Questionnaire (SIQ) and assessment for recent loss of a
      significant other. Also included were versions of the Beck Depression Inventory
      (Beck, 1967), Beck Hopelessness Scale (Beck, Schuyler, & Herman, 1974), Suicide
      Intent Scale (Beck et al., 1974), and Sarason's Social Support Questionnaire
      (Sarason, Levine, Basham, & Sarason, 1983) modified to retrospectively assess the
      period of time just prior to hospitalization. Classification of serious suicide
      attempt using both staff screening and the Suicide Intent Scale was validated by
      attempters' high scores on the SIQ. Data show that loss and low family support
      were the best predictors of an adolescent's suicide attempt. Also, suicide
      attempters reported more hopelessness than did nonattempters. The influence of
      recent loss on serious suicide attempts, especially when paired with a perceived
      lack of family support and hopelessness, provides evidence for a "stress
      vulnerability" model of adolescent suicide behavior.

PMID- 8266840
TI  - Adolescent runaways and family strife: a conflict-induced differentiation
      framework.
AB  - This paper explores the individual developmental and family system factors
      associated with running away. In the model presented, the ability of youth to
      successfully individuate is tied to the overarching tolerances for autonomy and
      intimacy that exist within the family system. Running away, in this perspective,
      is viewed as a conflict-induced effort on the part of youth to evolve a
      differentiated self when embedded within an individuation-inhibiting family
      system.

PMID- 8266841
TI  - Spanning the gender gap: gender differences in delinquency among inner-city
      adolescents.
AB  - The purpose of this investigation was to study the relationship between gender
      and delinquency among inner-city adolescents participating in a court diversion
      program. Official and self-report records of 64 adolescents were analyzed to
      determine the influence of gender on program referrals, arrest rates, drug use,
      delinquency, and gang involvement. Gender differences emerged in both the
      referral source and behavioral patterns of the adolescents. Overall, males were
      more likely to be referred to the program for violations of the law, to have been
      arrested, and to have engaged in aggressive offenses and selling drugs. Females
      were more likely to be referred because of status offenses. Gang membership had
      an intensifying effect on the delinquent behaviors of all youths. Male gang
      members were far more likely than nonmembers to have been arrested, and female
      gang members were more likely than nonmembers to carry weapons.

PMID- 8266842
TI  - Adoption as an option for unmarried pregnant teens.
AB  - Adolescent parenthood reduces the opportunities and optimal outcomes for both
      mother and child, yet pregnant teenagers rarely consider adoption. This paper
      reports a qualitative study that explored the reasons this option is so rarely
      examined. Twenty-one unmarried pregnant adolescents and their significant others
      were interviewed twice to determine the meaning adoption has for them. Four
      phenomena were found to be pivotal to the their willingness to consider adoption:
      (1) societal sanctions, (2) low level of knowledge, (3) anticipated psychological
      discomfort, and (4) lack of support from helping professionals. Information
      generated should be useful at health and social policy levels as well as to
      professionals who work with pregnant teenagers.

PMID- 8266843
TI  - Gender differences in the expression of depressive symptoms in middle
      adolescents: an extension of earlier findings.
AB  - Subjects in the present study were 153 French Canadian high school students (98
      females, 55 males) participating in the second phase of a larger longitudinal
      study (Baron & Groulx, 1990; Baron, Regimbald, & Groulx, 1991). The purpose of
      this study was to investigate whether, consistent with the findings obtained at
      the first phase of the study, females maintain higher mean scores than do males
      on all items discriminating between groups on the basis of gender. Separate
      discriminant function analyses of both the Reynolds Adolescent Depression Scale
      (RADS) and the Beck Depression Inventory (BDI); items were consistent, with lower
      mean scores for males on all interpretable items. Results are discussed with
      respect to variability in the instruments, and in view of previous research aimed
      at examining the expression of depressive symptoms in this and other adolescent
      samples.

PMID- 8266844
TI  - Toward a new understanding of early menarche: the role of environmental stress in
      pubertal timing.
AB  - A recent theory (Belsky, Steinberg, & Draper, 1991) suggests that environmental
      stress may trigger early menarche in adolescents. This is in contrast to a more
      traditional view that early menarche is biologically determined and serves as a
      risk factor for developing girls. The purpose of the present study was to examine
      two family stressors, divorce and interparental conflict, in light of the Belsky
      et al. theory. Participants were 71 adolescent females and their mothers. Of
      these, 44 were from intact families (i.e., the parents were married), and 27 were
      from divorced families. Age at first menarche was obtained via self-report.
      Maternal reports of interparental conflict as well as adolescent perception of
      conflict were obtained. Mothers reported on marital status. Results showed that,
      compared to girls from intact families, those from divorced families had an
      earlier onset of menarche. In addition, higher maternal reports of interparental
      conflict were significantly related to earlier menarche in the total sample.
      Results are discussed in relation to the Belsky et al. theory as well as
      traditional views of early menarche.

PMID- 8266845
TI  - Psychosocial correlates of adolescent drug involvement.
AB  - This study evaluates the ability of a four-factor psychosocial model to explain
      adolescent drug involvement. Subjects are a representative sample of seventh- and
      eighth-grade public school students. A cross-sectional sample of data was
      extracted from a multiyear longitudinal assessment of a statewide drug education
      program. Data were collected through administration of the Youth Life-Styles
      Inventory, a specially designed drug-involvement assessment instrument. The
      belief that substance use has both external (sociological) and internal
      (psychological) causes guided the selection of independent variables. Factor
      analysis was used to disclose the interrelated structures of the psychosocial
      variables. A four-factor model was produced offering a concise theoretical
      paradigm of the underlying psychosocial determinants of adolescent drug use. This
      model was regressed on two indexes of drug involvement. Findings should prove
      useful in policy formulation and design of adolescent drug education and
      treatment programs. The explanatory potency of the four-factor model should aid
      in the investigation of adolescent drug use. The results indicate the need for
      children to bond with peers, parents, and others who have drug-resistant
      attitudes, and with conventional institutions such as schools.

PMID- 8266846
TI  - Father's unemployment and adolescent's self-concept.
AB  - This study examined families in which fathers were affected by a steel mill
      shutdown, and tested hypotheses on the impact of unemployment on parent-child
      relations and adolescent self-concept. The hypotheses were tested by comparing
      convenience samples of three types of intact families with children between the
      ages of 12 and 18: continuously employed, unemployed with slight income loss,
      unemployed with significant income loss. As predicted, relationship with fathers
      were more negative when income loss was significant, but contrary to predictions,
      the relationship with mothers were not more positive, and adolescent self-concept
      was not directly affected by unemployment or income loss. However, a path
      analysis showed that income loss affected adolescent self-concept indirectly
      through its impact on parent-child relations.

PMID- 8266847
TI  - Middle adolescents' views of war and American military involvement in the Persian
      Gulf.
AB  - A sample of 189 eleventh graders in three different school locations (rural,
      urban, and suburban) was surveyed in order to (a) assess the effects of such
      variables as school setting, race, and gender on attitudes toward war; (b)
      examine attitudes toward the Persian Gulf War in relation to attitudes toward war
      in general; and (c) compare present-day attitudes with those identified in
      earlier studies concerning Vietnam and Latin America. While reactions to war were
      found to be associated with gender, race, and school setting, students in the
      present study were slightly less supportive of war in general, but more
      supportive of the Gulf War than were past subjects of the conflicts of their day.

PMID- 8266848
TI  - Perceptions of parental control and the development of indecision among late
      adolescent females.
AB  - Late adolescent females (N = 86; M age = 19.1 years) completed reliable and valid
      self-report measures on their perception of both parents' authority style
      (authoritarian, authoritative, permissive) and their own tendency toward
      decisional procrastination. Households where daughters perceived both parents as
      high authoritarian (n = 32) were significantly more likely to raise daughters
      with strong indecision tendencies than were parents perceived as low
      authoritarian (n = 23). Mothers and fathers perceived as high (n = 22) or low (n
      = 22) authoritative, and high (n = 32) or low (n = 24) permissive, did not
      produce significant differences in daughters' self-reported decisional
      procrastination. Results suggest that parental authority characterized by stern
      inflexibility and overcontrol has the greatest influence on daughters who develop
      chronic indecision tendencies.

PMID- 8266849
TI  - Student-faculty informal interaction and the effect on college student outcomes:
      a review of the literature.
AB  - Review of the literature synthesizes research on the informal interaction of
      college students and faculty. The role of student-faculty interaction is
      discussed with regard to effect on students' academic achievement, satisfaction
      with college, intellectual and personal development, persistence and attrition,
      and career and educational aspiration. Research supports the important
      socializing role of faculty in the college experience. Characteristics of the
      most interacting faculty personalities that interact most are given along with
      the classroom atmospheres most conducive to informal interaction. A review of
      research methodology for college student outcomes is presented.

PMID- 8266850
TI  - Impact of sodium-potassium citrate therapy on the circadian rhythm of urinary
      uric acid and urate saturation in normal individuals.
AB  - The circadian rhythm of the urinary saturation of uric acid, sodium acid urate,
      and ammonium acid urate was studied in 5 normal healthy male volunteers before
      and during 5 days of treatment with sodium-potassium citrate (1 g t.i.d., 1 g
      q.i.d., or 3 g t.i.d.). Urinary saturation was estimated on the relative
      supersaturation scale of Marshall and Robertson. Uric acid relative
      supersaturation varied during the day (mean +/- SD: -1.297 +/- 1.763) and peaked
      above the formation product between 5:30 and 8:00 am. The peak level was reduced
      (but not significantly) by each treatment regimen in comparison with the control
      day. Overall, critical supersaturation with uric acid was noted in 46 (13%) out
      of 345 urine specimens, occurring mostly (83%) between 5:30 and 8:00 am. The
      sodium acid urate relative supersaturation also varied during the day (mean +/-
      SD: 0.329 +/- 0.305) and peaked below the formation product between 8:00 and
      10:30 am. It was increased by each regimen (significantly by the 3 g t.i.d.
      regimen), but mostly remained in or below the metastable zone. The ammonium acid
      urate relative supersaturation also varied (mean +/- SD: 0.087 +/- 0.301) and
      peaked below the formation product between 5:30 and 8:00 am. The level was
      decreased by each regimen and remained in or below the metastable zone throughout
      the day. In conclusion, the early morning period was the time with the highest
      risk of urinary uric acid supersaturation, but this supersaturation could be
      reduced (although not significantly) by treatment with alkali citrate.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266851
TI  - [Vesicourethral function study and application of urinary alarm in progressive
      supranuclear palsy].
AB  - We performed a vesicourethral function study on seven patients with progressive
      supranuclear palsy. In storage phase, 6 patients had decreased urinary sensation
      and overactive detrusor. Although bladder compliance was normal in all patients,
      maximum cystometric capacity was decreased in 3 patients. In micturition phase,
      detrusor contraction was underactive in 4 patients and acontractile in 1 patient.
      Sphincter electromyogram showed detrusor-sphincter-dyssynergia in 1 patient, no
      decrease in 3 patients and synergistic decrease in 1 patient. Six patients had
      urinary incontinence partially due to those neurological abnormality, partially
      due to dementia and lower activity of daily living. To facilitate the care of
      such functional incontinence, we devised a urinary alarm. The urinary alarm is a
      device to detect urine in a diaper. One can know the micturition in a diaper
      without being informed of micturition by the patient and change diapers as soon
      as possible. It was also useful to examine their frequency/volume chart.

PMID- 8266852
TI  - Lectin immunohistochemical evaluation of human bladder carcinomas. A comparison
      of Carnoy's and formalin fixation.
AB  - A lectin immunohistochemical analysis of 51 human bladder carcinomas, including
      44 cases of transitional cell carcinoma (TCC) (G1, 15 cases; G2, 17 cases; G3, 12
      cases) and 7 cases of squamous cell carcinoma (SCC), was performed. Tissues were
      obtained by cold punch biopsies, fixed in Carnoy's or 10% formalin solution,
      stained for binding of 10 different lectins, and evaluated under the light
      microscope. The lectins used were concanavalin agglutinin (Con A), soybean
      agglutinin (SBA), Lotus tetragonolobus agglutinin (LTA), Dolichos biflorusa
      agglutinin (DBA), peanut agglutinin (PNA), Ricinus communis agglutinin I (RCA1),
      Ulex europaeus agglutinin I, II (UEA-I, II), wheat germ agglutinin (WGA), and
      Pisum sativum agglutinin (PEA). TCC prepared with Carnoy's fixation tended to
      show moderately positive Con A, UEA-I, and WGA reactions for G1, and strongly
      positive reactions for G2 and G3 lesions. UEA-II was mainly negative in G1, but
      tended to increase to become moderate in G3. DBA tended to show a moderately
      positive reaction in G1 and G2, but was mainly negative in G3. With formalin
      fixation, only RCA1 demonstrated grade specific variation, tendency to react
      moderately in the G1 and G2 cases, and strongly in G3. There were no further
      differences among the histopathological grades of TCC for other lectins. Thus,
      Carnoy's fixation appears superior for distinguishing between grades of lesions.
      SCC tended to react more strongly than TCC with all the various lectins except
      PEA, independent of fixation.

PMID- 8266853
TI  - [Clinical application of transrectal ultrasonic therapy to nonbacterial
      prostatitis and prostatodynia cases which were resistant to conventional drug
      therapy].
AB  - A total of 25 patients with nonbacterial prostatitis and prostatodynia which were
      resistant to conventional drug therapy underwent 5 minutes course of transrectal
      ultrasonic therapy in association with application of 1% hydrocortisone acetate
      cream to the anterior rectal wall for consecutive 8 days. The efficacy of the
      treatment was evaluated only by comparison of symptom scores for subjective
      symptoms obtained before and after treatment. Excellent results, which were
      defined as more than 70% reduction of symptom scores after treatment, were
      obtained in 5 (27.8%) among 18 evaluable cases in which symptom scores before
      treatment were more than 4, good (40-69% reduction of scores) in 4 (22.2%), fair
      (10-39% reduction of scores) in 4 (22.2%) and poor (less than 10% reduction of
      scores) in 5 (27.8%). Because of good clinical efficacy and the absence of
      complication, transrectal ultrasonic therapy combined with hydrocortisone acetate
      cream application was thought to be useful for the treatment of nonbacterial
      prostatitis and prostatodynia cases which responded poorly to the conventional
      therapy.

PMID- 8266854
TI  - [Clinical study on adenocarcinoma of the prostate].
AB  - A clinical study was performed on 75 patients with untreated prostatic cancer who
      had been hospitalized over a 5-year period. The age range was 52 to 90 years
      (median age: 72.3 years). The main complaint was dysuria in 73% of the cases.
      Thirty-two (43%) patients were smokers, and complications included bladder cancer
      in two and rectal cancer in one. The stages were T1 in 18 cases, T2 in 10, T3 in
      29 and T4 in 18, 28 cases were G1, 29 were G2, 11 were G3 and seven were G4.
      Among the tumor markers, PA sensitivity was the highest, but all markers showed
      high sensitivities in the T3 and T4 cases. Endocrinological treatment was
      performed on 74 patients. Survival rates showed significant differences only for
      the T and M classifications; no significant differences in survival rates
      according to the G classification, age of the patient or tumor markers were
      observed. Radiotherapy was suggested to be related to improvements in the
      prognosis only in patients with histological grading of G2.

PMID- 8266855
TI  - [Experimental studies on superinfection of acute simple urinary tract infection].
AB  - Experimental acute simple urinary tract infections were induced in female rats to
      determine whether low-virulent bacteria can reside in the simple urinary tract,
      whether minor flora can co-exist with major flora, and whether the bacterial
      population changes when antibiotics, to which major flora is sensitive and minor
      flora is resistant, is administered. "Enterococcus faecalis (E. faecalis) and
      Pseudomonas aeruginosa (P. aeruginosa) were instilled into the bladder
      transurethrally. Most rats had more than 1 x 10(4) CFU/ml of E. faecalis and P.
      aeruginosa two and four days after inoculation. Rats were divided into three
      groups. Mitomycin C injection group, acetic acid bladder instillation group,
      hydrocortisone injection group. E. faecalis (1 x 10(7) CFS/ml) and P. aeruginosa
      (1 x 10(4) CFS/ml) were instilled into the bladder. Bacterial count of E.
      faecalis was over 1,000 times that of P. aeruginosa in 14 rats two days after
      inoculation and in two rats six days after inoculation. Ampicillin (ABPC) was
      administered once a day for four days from two to five days after inoculation
      under the same condition. Bacterial count of E. faecalis was over 1,000 times
      that of P. aeruginosa in 26 rats two days after inoculation. The bacterial
      population changed in seven of the 26 rats after administration of ABPC, and in
      three of the 12 untreated rats.

PMID- 8266856
TI  - [Two cases of ganglioneuroma discovered as "incidentaloma"].
AB  - Two cases of adrenal ganglioneuroma discovered as "incidentaloma" are presented
      Case 1 was in a 29-year-old female who had a right adrenal tumor incidentally
      found by abdominal ultrasonography. The tumor was 26 g and 5.1 x 3.6 x 3.0 cm in
      size. She underwent surgical exploration and histopathologic examination revealed
      adrenal ganglioneuroma. Case 2 was in a 75-year-old man who had a right adrenal
      tumor detected during examination of microhematuria due to right renal stone by
      abdominal computed tomography. The tumor was 51 g in weight and 5.3 x 5.0 x 5.2
      cm in size. He underwent right adrenalectomy and histopathologic examination
      showed adrenal ganglioneuroma. Both patients had no abnormal endocrinological
      findings and the DNA histogram showed a diploid pattern.

PMID- 8266857
TI  - [A case of asynchronous renal cell carcinoma and urothelial cancer of the urinary
      bladder and left ureter].
AB  - A 49-year-old male with left renal cell carcinoma and urothelial cancer (bladder
      and residual left ureter), which asynchronously occurred, was reported. He had
      received radical nephrectomy due to renal cell carcinoma 12 years earlier. He was
      followed up by his local physician for 7 years postoperatively, during which time
      no metastatic lesion was detected. However, he presented with macroscopic
      hematuria on January 7, 1992, and a diagnosis of urinary bladder cancer was made
      at our hospital. Computerized tomography demonstrated a non-papillary, broad
      based tumor on the left wall of the urinary bladder, which histologically was
      transitional cell carcinoma (grade 3). Radical cystectomy, ureterectomy of the
      left residual ureter and ileal conduit were performed. Histological examinations
      showed that the urinary bladder tumor was transitional cell carcinoma, grade 3,
      pT-3b, and CIS (transitional cell carcinoma, grade 3) was found in the residual
      left ureter. Chemotherapy containing cis-platinum was performed as an adjuvant
      therapy, but multiple lung metastatic lesions appeared 2 months postoperatively,
      the histology of which was transitional cell carcinoma, suggesting metastasis
      from the urothelial cancer. Chemotherapy was ineffective, and he died of the
      disease 9 months after the operation. If this patient had been under long-term
      follow-up, the urothelial cancer may have been resected completely by
      transurethral resection. Our report indicated the importance of examination of
      the urinary tract in patients with such cancers, as well as the necessity of long
      term follow-up.

PMID- 8266858
TI  - [A case of renal cell carcinoma associated with von Hippel-Lindau disease].
AB  - We report a 27-year-old male with renal cell carcinoma associated with von Hippel
      Lindau disease. The patient was admitted to the department of internal medicine
      because of pneumothorax. At that time liver and pancreatic cyst, and renal tumor
      were found incidentally on the abdominal computerized tomography. He had a
      history of cerebellar hemangioblastoma, which had been removed in 1988.
      Angiography revealed multiple hypervascular tumors in the right kidney. We
      performed right radical nephrectomy, and histopathology showed clear cell type of
      renal cell carcinoma.

PMID- 8266859
TI  - [Nephrogenic adenoma of the ureter: a case report].
AB  - A 27-year-old male with nephrogenic adenoma of the ureter complicating
      urolithiasis is reported. Nephrogenic adenoma of the ureter is extremely rare,
      and this case is the sixth reported in Japan. The lesion was found at the site of
      the stone in the left ureter. Histopathologically, the tumor consisted of ducts
      resembling uriniferous tubules, and no signs of malignancy were noted. The cause
      of nephrogenic adenoma is considered to be metaplastic reaction to stimulation by
      stones and inflammation.

PMID- 8266860
TI  - [Two cases of continent cystoileostomy using nipple valve method].
AB  - We performed continent cystoileostomy in which the technique of Kock's efferent
      nipple was utilized, on two female patients with urethral cancer and vulvar
      cancer. We recommend continent cystoileostomy for the patient who needs
      urethrectomy but whose bladder function can be preserved.

PMID- 8266861
TI  - [Ileal low pressure bladder substitute with a tubular afferent limb: report of
      two cases].
AB  - We anastomosed the ileal reservoir to the membranous urethra in 2 male bladder
      cancer patients accepted for total cystectomy. Construction of the reservoir was
      performed according to Studer et al. (Br J Urol 63: 43-52, 1989). The procedure
      entails the use of 60 cm of ileal segment. The proximal segment, 15 cm, was left
      tubular to act as the inflow urinary tract. Anastomosis of the ureters to a
      tubular afferent ileal limb was carried out by end to side without anti-reflux
      method. The renal function was not changed by the operation. More than one year
      after the operation, urodynamic evaluation showed the reservoir to be low
      pressure with a capacity that increased to more than 400 ml. In both cases,
      however, about 300 ml residual urine was observed. Now both patients are
      performing intermittent self-catheterization and are continent night and day.
      When considering quality of life, this procedure is suitable whenever the urethra
      can be preserved after total cystectomy. For making a more "natural" bladder
      substitute, however, some modification of the operative procedure including anti
      reflux system may be required.

PMID- 8266862
TI  - [Spindle cell carcinoma of the urinary bladder: a case report].
AB  - A 74-year-old man with spindle cell carcinoma of the urinary bladder is reported.
      He presented to our clinic with gross hematuria resulting in bladder tamponade.
      Transurethral resection (TUR) was performed in order to control severe hematuria
      intractable with conservative therapy. Histologically the tumor invaded the
      muscle layer and was composed of two components, small foci of transitional cell
      carcinoma and numerous spindle cells with severe atypia and then the transition
      was recognized between them. Immunohistochemically transitional cell carcinoma
      was intensely positive for cytokeratin (CK) and epithelial membrane antigen
      (EMA), but negative for vimentin (VIM). Moreover some parts of spindle cells were
      weakly stained for CK and EMA. Three months after TUR, multiple pulmonary
      metastases and moderate right hydronephrosis occurred and he died of respiratory
      insufficiency one month later.

PMID- 8266863
TI  - Severe flare-up in a prostate cancer patient treated with luteinizing hormone
      releasing hormone analogue depot.
AB  - A 65-year-old man with advanced prostate cancer was treated with a luteinizing
      hormone-releasing hormone (LH-RH) analogue. Four days after the initial injection
      of 3.6 mg of goserelin acetate, severe dyspnea developed due to worsening
      pleuritis carcinomatosa, which was considered as a flare-up. Chest drainage was
      required to save his life. Therefore, we emphasize the importance of treatment to
      prevent tumor flare during LH-RH analogue therapy.

PMID- 8266864
TI  - [Detection of human papillomavirus DNA in condyloma acuminatum of the urethra: a
      case report].
AB  - A case in a 35-year-old male with recurrence of the condyloma acuminatum of the
      urethra is presented and the involvement of human papilloma virus (HPV) with this
      disease is mentioned. The HPV-DNA in the excised specimen was detected by the dot
      blot hybridization method with radiolabelled RNA probes, and the type of the DNA
      was investigated by the Southern blot hybridization method with biotinylated DNA
      probes, which could detect the HPV-DNA of types 6, 11, 16, 18, 31, 33 and 35.
      These analyses demonstrated the HPV-DNA of type 11 and another unidentified type
      in our case. From the literature with regard to the etiology of this disease
      considering the risk of malignancy, we also emphasize the necessity for close
      observation of the patients with condyloma acuminatum, clinically benign, which
      contains the so-called malignant type HPV-DNA.

PMID- 8266865
TI  - A case of parameatal urethral cyst with calculi.
AB  - Parameatal urethral cyst is very rare. Although 15 cases have been reported in
      Japan, no case of parameatal urethral cyst with calculi has previously been
      reported. We report the first case of parameatal urethral cyst with calculi in a
      22-year-old female patient.

PMID- 8266866
TI  - [A case of clear cell adenocarcinoma of the female urethra].
AB  - A 49-year-old female visited our hospital because of bloody discharge from the
      urethra. On examination, an elastic-soft mass was palpable beneath the anterior
      vaginal wall. The vaginal mucosa was intact. Cystourethroscopy demonstrated
      neither tumor nor diverticular orifice. Pathological specimen obtained by needle
      biopsy revealed clear cell adenocarcinoma. The patient underwent anterior pelvic
      exenteration and modified Kock pouch urinary diversion. The microscopic
      appearance suggested that the tumor arose from the paraurethral duct. Stains for
      prostatic specific antigen and prostate specific acid phosphatase were negative.
      Forty cases of clear cell adenocarcinoma of the female urethra reported in the
      literature were reviewed.

PMID- 8266867
TI  - [Tuberculosis of the female urethra: a case report].
AB  - A 52-year-old female with the chief complaint of miction pain was referred for
      the examination of a urethral nodule. Physical inspection revealed the meatus to
      be reddish and swollen. The painless nodule (1 x 1 x 2 cm) was situated between
      the urethra and vagina on transvaginal examination. Chest X-ray, drip infusion
      pyelography (DIP) and urethrocystography (UCG) showed no evidence of
      tuberculosis. Bladder mucosa was normal on cystoscopy. Mycobacterium tuberculosis
      was not detected from urine or sputum. The nodule was resected along with a
      portion of the urethra. Histopathological examination revealed tuberculous
      granuloma of the urethra.

PMID- 8266868
TI  - [Syphilitic orchitis: report of a case].
AB  - Syphilitic orchitis ir recently a rare disease in Japan. A 44-year-old man
      visited our hospital with the complaint of swelling of the right scrotum. He
      first noticed it about a half year ago, but the swelling mitigated without any
      therapy. The right testis was about the size of a hen's egg, elastic hard, and
      slightly rugged when he first visited our hospital. Treponema pallidum
      hemagglutination assay (TPHA) and rapid plasma reagin (RPR) were positive. We
      performed high orchiectomy because we could not deny the possibility of
      testicular tumor. Pathologically, granulomatous inflammation with lympho
      plasmacytic infiltration and endoarteritis obliterans of the small arteries were
      seen in the specimen. It was diagnosed as granulomatous inflammation possibly
      caused by syphilitic orchitis. Syphilitic orchitis is usually quite difficult to
      distinguish from other types of granulomatous diseases of the testes, for example
      tuberculous orchitis. Various types of stains and careful examination of the
      specimen were thought to be necessary to distinguish these diseases.

PMID- 8266869
TI  - [Study of risk factors for prostatic cancer].
AB  - A case-control study was conducted on 294 prostatic cancer patients and controls.
      General population controls were chosen from 13 areas in Gunma Prefecture and
      were matched by age (+/- 2 y.o.) to cases. Odds ratio (O.R.) and 95% confidence
      interval (C.I.) were calculated on each item according to group; 69 years old or
      younger and 70 years old or older, and age-adjusted O.R. and 95% C.I. were
      calculated. Risk factors of prostatic cancer were investigated. There was a
      significantly higher risk for prostatic cancer in those 1) engaged in
      agriculture, forestry or fishery (< or = 69, > or = 70, total), 2) shaving 1/3
      days or less frequently (> or = 70, total), 3) having thin pubic hair (total), 4)
      phimosis (< or = 69, total), 5) having history of smoking (> or = 70, total), 6)
      history of smoking 50 years or more (total), 7) having eaten vegetables rarely (>
      or = 70, total), 8) having past history or complication of asthma (> or = 70).
      O.R.s of having past history or complication of benign prostatic hypertrophy,
      prostatitis and urethral stricture were high significantly, but they were
      supposed to be caused by bias. Four patients had first degree family members who
      suffered from prostatic cancer, compared to zero in the control. There was a
      significantly lower risk for prostatic cancer in those 1) engaged in office work
      (> or = 70, total), 2) blood type A or AB (< or = 69), 3) having had one child or
      none (total), 4) having past history or complication of tuberculosis
      (total).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266870
TI  - [Correlation between atmospheric temperature and testicular torsion].
AB  - A study on correlation between testicular torsion and atmospheric temperature was
      made based on 39 patients observed at Tokai University Hospital. Testicular
      torsion did not occur in any of the 39 patients in the summer (June to August),
      but occurred in 14 patients in spring (March to May), in 13 patients in autumn
      (September to November), and in 12 patients in winter (December to February). The
      onset hour was between 04:00 p.m. and midnight in 20 patients (54.1%), between
      midnight and 08:00 a.m. in 13 patients (35.1%), and between 08:00 a.m. and 04:00
      p.m. (in the daytime) in only 3 patients (10.8%). In each of 38 patients, the
      atmospheric temperature at the onset hour was investigated on the basis of
      meteorological observations made by the fire department located in the region of
      the patient's residence. The data indicated that testicular torsion in 29
      patients (76.3%) occurred below 15 degrees C (below the average temperature in
      Kanagawa Prefecture). Furthermore, a correlation (Spearman's coefficient above
      95%) between reduction in temperature and onset frequency was noted. Evidently
      these findings suggest that the incidence of testicular torsion tends to increase
      with reduction in temperature.

PMID- 8266871
TI  - [Milk of calcium renal stone in a patient with ureteral tumor: a case report].
AB  - We report a case of milk of calcium renal stone within a calyceal diverticulum in
      the patient with left ureteral tumor. The patient was a 77-year-old-man with the
      chief complaint of asymptomatic microscopic hematuria. A plain film revealed
      round opaque calcific densities in the left kidney in the supine position and a
      dense crescent-shaped shadow with a horizontal border in the upright position. An
      intravenous pyelography showed left hydronephrosis and calculi within a calyceal
      diverticulum. Computed tomography in the supine position revealed layering of the
      calcifications in cystic lesion of the left kidney accompanied by left
      hydronephrosis due to a soft mass in the left ureter and a right renal cyst.
      Retrograde pyelography revealed a filling defect of the middle portion of the
      left ureter. Under the diagnosis of milk of calcium renal stone and left ureteral
      tumor, left total nephroureterectomy and partial cystectomy was performed.
      Pathological findings indicated transitional epithelium of the diverticulum wall
      and grade 1 transitional cell carcinoma of the left ureteral tumor.

PMID- 8266872
TI  - [A case of renal cell carcinoma effectively treated by interferon-alpha and
      embolization of the renal artery].
AB  - A case of renal cell carcinoma effectively treated by interferon-alpha and the
      embolization of the left renal artery is reported. A 69-year-old man was referred
      to us because of a left renal mass. We made a diagnosis of a left renal tumor
      with tumor thrombus in the renal vein and inferior vena cava, and multiple lung
      metastases by imaging examinations. At first the embolization of the left renal
      artery was selected and interferon-alpha treatment was performed for 3 months. At
      3 months after the embolization, the metastatic lung tumors had completely
      disappeared and the left renal tumor and the tumor thrombus were reduced in size,
      so that left radical nephrectomy was performed. Pathological examination revealed
      that a small part of the tumor was viable renal cell carcinoma. After the
      operation, interferon-alpha treatment has been continued for 15 months and
      recurrence and metastasis have not been detected.

PMID- 8266873
TI  - [Ureteritis cystica diagnosed by biopsy under a ureteroscope: a case report].
AB  - We report a case diagnosed as ureteritis cystica by ureteroscopic examination. A
      65-year-old female was admitted to our hospital for a thorough examination of
      anasarca and reduction of renal function. Computerized tomography showed atrophy
      in the right kidney and hydronephrosis in the left kidney. Nephrostomy was
      performed and antegrade pyelography showed ureteral stenosis. For the purpose of
      accurate diagnosis of ureteral stenosis, ureteroscopy and biopsy were performed.
      Histological examination revealed ureteritis cystica. Fifty-five cases including
      this case, reported in Japan, are herein reviewed.

PMID- 8266874
TI  - [Ureteral obstruction caused by aneurysm of iliac artery].
AB  - A 76-year-old man was referred to our hospital because of right hydronephrosis. A
      retrograde pyelogram showed obstruction of the right ureter at the level where it
      was crossed by the common iliac artery. A computerized tomography scan
      demonstrated an encased right ureter and aneurysm of right common iliac artery.
      Arteriography revealed aneurysm of right common iliac artery. An aorto-iliac
      graft bypass and ureterolysis were performed with intra-peritoneal displacement
      of the right ureter. The diagnostic procedures and treatment modalities for
      ureteral obstruction caused by aneurysm are discussed.

PMID- 8266875
TI  - [Bladder cancer associated with growth hormone-producing pituitary tumor: a case
      report].
AB  - A case of bladder cancer associated with a growth hormone (GH) producing
      pituitary tumor is reported. A 67-year-old male underwent hypophysectomy for a GH
      producing pituitary tumor, 31 months earlier. Although the serum GH decreased
      postoperatively, recurrence of pituitary tumor with increased serum GH was found
      and followed by a neurosurgeon. He was referred to our department for
      asymptomatic gross hematuria. Cystoscopy revealed a papillary pedunculated tumor.
      Under the diagnosis of superficial bladder tumor, transurethral resection (TUR)
      was performed. Pathological examination showed transitional cell carcinoma. As
      the bladder cancer recurred with a high level of serum GH seven months later, TUR
      was repeated. We reviewed and discussed the relationship between GH or GH
      producing tumor and bladder cancer.

PMID- 8266876
TI  - Paraparesis due to metastatic prostatic cancer effectively treated with a high
      dose of diethylstilbestrol diphosphate: a case report.
AB  - A case of paraparesis due to thoracic vertebula metastasis of prostate cancer is
      reported. Treatment through a high dose of diethylstilbestrol diphosphate (DES-P)
      was very effective. Two and a half years later, the patient is ambulatory and
      relapse has not occurred. We recommend the use of a high dose of DES-P for spinal
      cord compression due to prostate cancer, instead of laminectomy or radiation.

PMID- 8266877
TI  - [Three cases of vas deferens calcification].
AB  - Three patients with calcification of the bilateral vas deferens, revealed by
      plain X-ray, pelvic computerized tomography and/or vesiculography, are reported.
      Although they came to our department because of acute left epididymitis, right
      ureteral calculus and right undescended testis respectively, these diseases were
      not the causative factors for the calcification. Since no other probable causes
      including tuberculosis and diabetes-mellitus were found, the cause of disease was
      unknown.

PMID- 8266878
TI  - [Malignant fibrous histiocytoma of the spermatic cord: a case report].
AB  - A case of malignant fibrous histiocytoma of the spermatic cord is reported. A 44
      year-old man was admitted because of a painless, gradually enlarging mass in the
      left scrotum. Local tumor excision and subsequent radical inguinal orchidectomy
      was performed. The histological diagnosis was malignant fibrous histiocytoma.
      There were no signs of recurrence or metastasis 8 months after the operation.
      Malignant fibrous histiocytoma in the spermatic cord is rare. We reviewed 34
      previously reported cases. The rate of local recurrence and distant metastasis
      are 34.5% and 17.2%, respectively.

PMID- 8266879
TI  - [Treatments of staghorn calculi].
AB  - The treatment of staghorn calculi is still difficult even though urolithiasis
      treatment can now be performed by endourology and extracorporeal shock-wave
      lithotripsy (ESWL) without open surgery. Because of the variety in volume and
      pattern of the staghorn calculi, especially with or without dilated renal pelvis
      and calyces, selection of treatment methods is important. The combined method of
      percutaneous nephrolithotomy (PNL) and ESWL has been highly effective in the
      complete removal of most staghorn calculi. Developments of the ESWL instrument
      and tools have increased the success of less invasive ESWL monotherapy with
      placing of stent or percutaneous nephrostomy for staghorn calculi with nondilated
      calyces. Also the treatment methods should be selected depending upon the
      components of the staghorn calculi. Dissolution and solidity, which are affected
      by the components, are also important factors. Complete removal of staghorn
      calculi is very difficult, and almost impossible to be performed in only one
      occasion including other surgical procedures as a series and this is the existing
      insurance provision. Therefore, we await the creation of a new insurance
      provision for the treatment of staghorn calculi.

PMID- 8266880
TI  - [Treatment of staghorn calculi on the basis of composition and structure].
AB  - Most staghorn calculi are infection stones composed of struvite and/or carbonate
      apatite. Sometimes, cystine, uric acid, whewellite and brushite stones also
      assume a staghorn configuration when located in the kidney. It is very important
      in stone crushing to know the composition and architecture of the stones.
      Struvite stones show a concentric laminal structure and are fragile because of
      wide interstices of crystals and rich organic matrix. These stones usually
      contain many bacterial colonies in the interstices of crystals and bacteria break
      out of the stones when they are crushed. Therefore, perioperative administration
      of antibiotics is necessary for prevention of bacteremia and sepsis. Whewellite
      stones and uric acid stones have a smooth surface and reveal compact radial and
      laminal structure especially in the peripheral layer. They are very hard and are
      refractory to crushing, and the fragments are large. Cystine stones show a
      compact radial monomineral texture and are very hard. The fragments made by
      crushing are large. Therefore, combination therapy of stone crushing and
      irrigation of alkali solution may be useful for treatment of cystine stones as
      well as uric acid stones. Calcium phosphate stones, hydroxyapatite or brushite
      stones, are rare and are formed in hyperparathyroidism, Cushing syndrome and
      renal tubular acidosis. Hydroxyapatite stones are rich in matrix and fragile.
      Brushite stones reveal radiate structure and are hard. There is no general method
      of treatment for staghorn calculi but we should select the most reasonable method
      including open surgery for each case taking into consideration the stone
      composition, predisposing factors and possibility of stone residue and
      recurrence.

PMID- 8266881
TI  - [Combination therapy of ESWL and PNL for the staghorn calculi].
AB  - We have been engaged in the treatment of urinary tract calculi using
      extracorporeal shockwave lithotripsy (ESWL) and endourology techniques for more
      than 8 years. In the treatment of thin staghorn calculi, ESWL monotherapy is the
      first choice. On the other hand, combination of percutaneous nephrolithotomy
      (PNL) and ESWL is important for the treatment of thick staghorn calculi in order
      to avoid the stone street and side effects of shock waves. When the stone is made
      of hard components such as calcium oxalate monohydrate and cystine, combination
      of both methods is also useful. In the case of complicated staghorn calculi with
      isolated branches, open surgery such as nephrolithotomy or partial nephrectomy
      might be the choice.

PMID- 8266882
TI  - [Treatment of staghorn calculi--ESWL monotherapy].
AB  - We investigated 41 cases (44 kidneys) of renal staghorn calculi treated in our
      hospital between November, 1988 and July, 1992. The efficacy of each treatment
      was 83.3% for extracorporeal shock-wave lithotripsy (ESWL) monotherapy (27
      kidneys), 40% for percutaneous nephrolithotomy (PNL) with ESWL (5), 100% for
      dissolution with ESWL (6), 50% for pyelolithotomy with ESWL (2), 100% for
      nephrolithotomy with ESWL (1), and 100% for only dissolution (1). In the ESWL
      monotherapy group except for 3 cases that had complete staghorn calculi with
      severe caliectasis, the efficacy was between 70% and 100%, and the term of
      hospitalization was only about 1 month. The complications of ESWL monotherapy
      were stone street itself and high fever caused by it. However, renal function,
      could be successfully preserved by the timely drainage with D-J stent or
      nephrostomy tube. Thus, in most cases of staghorn calculi as well as other
      urolithiasis, ESWL monotherapy seemed to be more effective and safe than combined
      therapy of PNL and ESWL.

PMID- 8266883
TI  - [The treatment of staghorn calculi].
AB  - Between May 1989 and November 1991, 19 staghorn calculi were treated by
      extracorporeal shock-wave lithotripsy (ESWL) with a Dornier MFL 5000 or Northgate
      SD-3. The 19 calculi were evaluated. Treatment was with monotherapy by ESWL in 9,
      combination percutaneous nephrolithotomy (PNL)-ESWL in 9, and nephrostomy in 1.
      Of the patients, 14 had a cross stent catheter pre-ESWL treatment to improve
      fragment evacuation. Radiologic follow up in 19 kidneys revealed that 57.9% were
      stone free. We arbitrarily separated our cases into 3 groups: struvite renal
      calculi, calcium carbonate calculi and others. Result of stone-free rate was 100%
      for stones consisting of struvite, and 14. 3% for stones consisting of calcium
      carbonate. In our opinion, the best indication of monotherapy by ESWL is for
      staghorn calculi, which consists of struvite, without marked dilation of pelvis
      and calyces.

PMID- 8266884
TI  - [Treatment of staghorn calculi by extracorporeal shock wave lithotripsy
      monotherapy].
AB  - We evaluated retrospectively 107 patients with staghorn calculi who underwent
      extracorporeal shock wave lithotripsy (ESWL) monotherapy from 1985 to 1990. The
      107 patients consisted of 65 complete staghorn calculi and 55 partial staghorn
      calculi. Staghorn calculi required an average of 4.3 treatment sessions. Using a
      Dornier HM3 lithotriptor, the stone-free rate was 33% in patients with complete
      staghorn calculi, and 35% in patients with partial calculi. For stone evacuation
      following ESWL procedure, ureteral stenting, nephrostomy and transurethral
      lithotripsy were necessary. Four of the 21 patients who underwent ESWL
      monotherapy and were available for long-term followup showed stone growth, while
      all of the 10 patients who underwent open surgery during the previous 5 years
      became stone free. The average period of hospitalization and cost were 38.3 days
      and 700,000 yen in patients who had received open surgery, and 25.8 and 1,720,000
      yen in patients receiving ESWL monotherapy. In conclusion, ESWL monotherapy is
      useful, and if patients require complete removal of all stone fragments, a
      percutaneous lithotripsy should be performed following ESWL monotherapy.

PMID- 8266885
TI  - [Treatment of staghorn calculi: combined therapy and stone recurrence].
AB  - Between April 1986 and September 1992, 29 extensive staghorn calculi were treated
      in 24 patients. Treatment was with extracorporeal shock-wave lithotripsy (ESWL)
      monotherapy in 11, initial ESWL followed by percutaneous nephrolithotomy (PNL) in
      7 and initial PNL followed by ESWL in 11. A comparison based on treatment
      demonstrated that initial PNL followed by ESWL resulted in a lower rate and
      shorter duration of the "stone street" while stone-free rate at 1 year after the
      last treatment, recurrence rate, residual stone-growth rate and other
      complication rates were similar. Initial PNL followed by ESWL should be
      considered the efficacious treatment option, especially for patients with
      extensive traghorn calculi.

PMID- 8266887
TI  - Intraluminal pressure variations in the isthmus of the porcine oviduct after
      intrauterine insemination with saline, oestrogen solution or boar seminal plasma.
AB  - The purpose of this study was to investigate if an intrauterine deposition of
      saline, boar seminal plasma, or an oestrogen solution containing 11.5 micrograms
      oestrogens affected the intraluminal pressure in the isthmus of the oviduct in
      unrestrained gilts. In order to monitor variations in intraluminal pressure, 2
      ultra-miniature pressure sensors, located at 2 different points along the same
      isthmus were used. After an initial recording period, either saline, boar seminal
      plasma, or the oestrogen solution was deposited directly into the uterus.
      Intraluminal pressure recordings were conducted up to 6 h after insemination, and
      blood samples, for monitoring oestradiol-17 beta and 15-ketodihydroprostaglandin
      F2 alpha levels, were collected. None of the inseminates had any consistent
      effect on the intraluminal pressure in the porcine oviduct. After deposition of
      the oestrogen solution, increases in the circulating levels of both oestradiol-17
      beta and 15-ketodihydroprostaglandin F2 alpha were seen.

PMID- 8266886
TI  - [Treatment of patients with staghorn calculi by means of extracorporeal shock
      wave lithotripsy (ESWL)].
AB  - Between August, 1987 and December, 1991, 84 patients with 87 staghorn calculi
      were treated mainly with extracorporeal shockwave lithotripsy (ESWL) using a
      Dornier HM-3 improved lithotriptor. Patients were 38 men (38 renal units, mean
      age 54.9 years) and 46 women (49 renal units, mean age 54.3 years). Staghorn
      calculi were divided into 2 types; 54 units of complete type (mean stone area 9.2
      cm2) and 34 units of incomplete type (mean stone area 5.5 cm2). Patients with
      complete type were treated with 3.6 sessions and 7,779 shock waves on average and
      31.6 days for hospitalization was required, while patients with incomplete type
      were treated with 2.4 sessions and 5,288 shock waves on average and 15.7 days for
      hospitalization was required. After treatment, the excellent rate was 47.2% for
      the complete type and 44.1% for the incomplete type. After the monotherapy of
      ESWL the excellent rate was 46.9% and after the combined therapy with
      percutaneous nephrolithotripsy (PNL) and/or percutaneous nephrostomy (PCN) it was
      43.5%. We considered that the ESWL monotherapy for staghorn calculi was not
      feasible in patients with a large stone volume, with severe hydrocalices, with
      cystine stones and with so-called "complex staghorn calculi".

PMID- 8266888
TI  - The effect of induced standing reflex, cervical stimulation and insemination on
      intraluminal pressure variations in the isthmus of the oviduct in unrestrained
      gilts.
AB  - Four gilts were each equipped with 2 ultra-miniature pressure sensors, placed at
      2 different points along the same isthmus of the oviduct, on the morning of the
      first day of standing oestrus (Day 1). Intraluminal pressure recordings were
      started the same afternoon. After an initial recording period, intraluminal
      pressure was recorded while the gilts showed standing oestrus and during cervical
      stimulation followed by insemination with either 100 ml saline or 100 ml boar
      semen. Monitoring of the pressure variations in the isthmus was continued for up
      to 6.5 h after the last insemination. Blood samples for monitoring oestradiol-17
      beta, progesterone and 15-ketodihydroprostaglandin F2 alpha were collected before
      and after each manipulation of the gilt and every 30 min during the rest of the
      test period. None of the above manipulations had any consistent effect on the
      intraluminal pressure in the porcine isthmus, although, a clear 15
      ketodihydroprostaglandin F2 alpha peak could be seen after insemination with boar
      semen.

PMID- 8266889
TI  - A study on the effects of inhibition of prostaglandin biosynthesis with flunixin
      meglumine and later administration of prostaglandin F2 alpha on the intraluminal
      pressure variations in the isthmus of the oviduct in unrestrained gilts.
AB  - Three gilts were each equipped with 2 ultra-miniature pressure sensors, placed at
      2 different points along the same isthmus of the oviduct. Following base
      recordings of isthmic intraluminal pressure, the gilts were treated with 2.2 mg
      flunixin meglumine (FM) per kg body weight. After FM treatment, the peripheral
      plasma levels of 15-ketodihydro-PGF2 alpha, the major metabolite of prostaglandin
      F2 alpha (PGF2 alpha), decreased within 30 min. The frequency of the phasic
      pressure fluctuations in the isthmus of the oviduct decreased after FM treatment.
      Exogenous administration of PGF2 alpha increased the peripheral plasma levels of
      15-ketodihydro-PGF2 alpha. When administered at a dose of 0.1 mg, PGF2 alpha
      produced an increase in the frequency of the phasic pressure fluctuations in the
      oviductal isthmus. When the PGF2 alpha dose was increased to 0.5 mg, a marked
      increase in the base and total pressures was seen in addition to the increase in
      the frequency of the phasic pressure fluctuations.

PMID- 8266890
TI  - Estimation of herd incidence of infection with bovine virus diarrhoea virus
      (BVDV) in herds previously without animals persistently infected with BVDV.
AB  - On a previous occasion, all animals in 9 herds had been bled for bovine virus
      diarrhoea virus (BVDV) and antibodies. No animals persistently infected (PI) with
      BVDV were detected. Three years later 10 animals in each herd were tested again.
      By this time 60 out of 90 previously seronegative animals had seroconverted.
      Seroconversions had occurred in 8 of the 9 herds corresponding to a incidence
      risk of herd infection of 0.52 per year. The incidence risk of seroconversions in
      individual animals was 0.31. Examination of young stock for antibodies and
      determination of antibody titer in bulk milk were good indicators for ongoing
      infections in the herds. The number of herd infections seemed to be higher than
      could be explained from purchase of PI animals.

PMID- 8266891
TI  - Attempts at preventing further spread of bovine virus diarrhoea virus (BVDV)
      infection in 5 Danish dairy herds in which BVDV had been isolated.
AB  - In 5 herds in which bovine virus diarrhoea virus (BVDV) had been isolated, all
      animals were bled for virological and serological examination. After the herd
      blood test, follow up blood tests were made on calves born up to 6 months later
      in 1 herd, 9 months later in 1 herd and up to 12 months later in 3 herds.
      Persistently infected animals (PI animals) were removed and after a time period a
      small herd sample of 10 animals that were born after removal of the PI animals
      were examined for BVDV antibodies. At the herd blood test a total of 21 PI
      animals were detected. During the follow up period another 25 PI animals were
      born. Among animals in the small herd samples collected after removal of the PI
      animals, antibody positive animals were found in the 2 herds with the shortest
      follow up period. In the 3 herds with a 1 year follow up period there were no
      antibody carriers in the herd sample. It seems possible to prevent further spread
      of infection with BVDV if all animals in the herds as well as animals born during
      the following year are examined and PI animals removed.

PMID- 8266892
TI  - Isolation of Listeria monocytogenes from goat cheese associated with a case of
      listeriosis in goat.
AB  - Listeria monocytogenes was isolated from the brain of a goat, which was
      euthanized due to listeriosis. A few weeks later a similar subtype of L.
      monocytogenes was isolated from an on-farm manufactured fresh cheese which did
      not contain any milk from the goat which had suffered from listeriosis. A similar
      subtype was also found on 1 of the shelves in the refrigerator where cheeses were
      stored. Prior to the onset of listeriosis, 1 fresh cheese had been made of milk
      from the actual goat, which may have excreted L. monocytogenes in her milk. Thus,
      the cheese made of this milk may have contaminated the shelves in the
      refrigerator which then has served as a Listeria reservoir for new cheeses during
      several weeks.

PMID- 8266893
TI  - Pathological lesions in the right and left porcine lung: evaluation of an
      alternative method for scoring pneumonic lesions based on right lung examination.
AB  - Plucks from 2,372 sows, gilts and slaughterswine (originating from 3 independent
      sources) were evaluated for presence and severeness of 6 different pathological
      entities. Results were calculated for each of the lungs separately and compared
      to the combined findings of both lungs. Both qualitatively (comparing relative
      test sensitivities) and quantitatively (comparing lung scores), the right lung
      results were more optimal than the left lung outcomes and relatively consistent
      among the 3 data sets. The over-all right lung relative sensitivities for the
      detection of catarrhal pneumonia or chronic pleuritis were 81.3% and 72.0%,
      respectively. The over-all differences in the right minus left lung scores for
      the 2 lesions were +13.0% and +9.0%, respectively. The necessary sample size of
      right lungs to detect at least 1 lung with catarrhal pneumonia or chronic
      pleuritis is presented along with a method for calculating confidence intervals.

PMID- 8266894
TI  - Acute metabolic effects of clenbuterol in calves.
AB  - The acute metabolic effects of clenbuterol were studied in calves. Clenbuterol
      was given intravenously at a dose of 1 microgram/kg body weight. Glucagon was
      used to increase insulin secretion. Pretreatment with clenbuterol did not change
      the glucagon-induced hyperglycaemia, but the serum levels of insulin were
      significantly higher. Clenbuterol showed a significant lipolytic effect. The post
      prandial increases in glucose and insulin were significantly higher in
      clenbuterol treated calves. The findings are in accordance with results from
      earlier studies where clenbuterol was given orally in much higher doses.

PMID- 8266895
TI  - Excretion of Eimeria oocysts in calves during their first three weeks after turn
      out to pasture.
AB  - The numbers of Eimeria oocysts per gram (opg) and the dry matter content of 449
      faecal samples taken from 54 calves in 8 herds in south west Sweden were
      determined during the last 2 weeks before and the first 3 weeks after the animals
      were turned out to pasture. While they were housed only between 0 and 580 opg
      were found and in 2 of the herds the numbers of oocysts remained low after turn
      out. In the other 6 herds the numbers of oocysts increased after 8 to 10 days and
      reached a peak of between 1080 and 80,803 opg 9 to 18 days after turn-out. By 21
      to 24 days after turn-out the opg-values had declined to their initial levels.
      Eimeria alabamensis accounted for most of the increase, but small numbers of
      oocysts of E. auburnensis, E. bovis, E. bukidnonensis, E. cylindrica, E.
      ellipsoidalis, E. pellita, E. subspherica, E. wyomingensis and E. zuernii were
      also observed. The interval between turn-out and the start of the increase in
      excretion of oocysts corresponded closely to the prepatent period of E.
      alabamensis and overwintered oocysts were therefore the most likely source of the
      infection. In 6 of the herds the dry matter content of the faeces of the calves
      decreased after turn-out and 56% of the calves had clinical diarrhoea. Although
      it cannot be excluded that change of diet may have contributed to these symptoms,
      E. alabamensis infection is suggested as a potential cause of diarrhoea and loss
      of condition in calves in Sweden during their first weeks on pasture.

PMID- 8266896
TI  - Histopathology of experimental Schistosoma bovis infection in goats.
AB  - The inflammatory host response to Schistosoma bovis in young goats was studied at
      necropsy by light microscopy 34 weeks after primary exposure to 3,000 cercariae
      (group B, n = 6), 34 weeks after primary exposure to 3,000 cercariae followed by
      challenge with 2,500 cercariae at week 17 (group C, n = 5), and 17 weeks after
      primary exposure to 2,500 cercariae, given on week 17 of the experiment (group D,
      n = 6). Three goats served as uninfected controls. The faecal egg output had been
      minimal for 17 weeks prior to necropsy in groups B and C and only for the last 2
      weeks in group D. Histological studies were carried out on the small intestine,
      liver, lung and spleen, and tissue egg counts were performed. In sections of the
      small intestine and liver, a panel of histopathological variables were
      quantitated to characterize the host response and differences between groups of
      animals were evaluated with one way analysis of variance. The mean tissue egg
      count in the small intestine was slightly but not significantly higher in group C
      than group B and about twice as high in group D (D vs B or C p < 0.01). Group
      means of numbers of inflammatory foci per section of gut wall corresponded well
      with those of tissue egg counts, suggesting that the rate of inflammatory
      destruction of eggs did not differ markedly between the groups.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266897
TI  - Pathogenicity and immunity studies of Haemophilus parasuis serotypes.
AB  - After intranasal inoculation of SPF pigs with the 7 reference strains of
      Haemophilus parasuis only the reference strains of serotypes 1 and 5 proved to be
      pathogenic and were able to produce the lesions characteristic of Glasser's
      disease. Even though the reference strains of serotypes 2, 3, 4, 6 and 7 proved
      to be apathogenic, intranasal inoculation resulted in the development of
      circulating antibodies as demonstrated by the complement fixation test. This
      serological response suggests an antigenic relationship between serotypes 1 and 3
      different from the relationship seen among serotypes 2, 4, 5, 6 and 7. Pigs given
      an aerosol with the apathogenic serotypes 2, 3, 4 and 7, respectively, resisted
      challenge with a virulent Danish strain of serotype 5. These results indicate
      that the 7 serotypes also have antigenic determinants in common and that these
      determinants elicit cross-protecting immunity on the respiratory mucosa.

PMID- 8266898
TI  - Rabies antibody titres in vaccinated reindeer.
AB  - One dose of inactivated, adjuvanted rabies vaccine of cell culture origin
      (Rabisin) induced good but short-duration immunity in close to 100% of the 50
      semi-domesticated reindeer (Rangifer tarandus tarandus L.) vaccinated. Most of
      the animals (44) had rabies virus antibody titre > or = 1.5 IU/ml at 38 days
      after vaccination. Five animals had titre 0.5 IU. Antibody titres were not,
      however, present 1 year after primary vaccination in most animals. About 1 year
      (360-413 days) after primary vaccination, 22 of the 39 reindeer that could be
      sampled had rabies virus antibody titre < 0.5 IU/ml.

PMID- 8266899
TI  - Morbidity, mortality and coronavirus antigen in previously coronavirus free
      kittens placed in two catteries with feline infectious peritonitis.
AB  - Serologically coronavirus free kittens were placed in 2 catteries with a history
      of feline infectious peritonitis (FIP), each cattery representing 1 of the 2
      different predominant clinical characteristics of FIP--effusive and
      granulomatous. The kittens were clinically observed for 100 days. A 100%
      morbidity and a 90% mortality was observed. The first signs were observed after
      14 and 27 days respectively. The clinical pattern of the disease was similar in
      all kittens and showed a pattern of recurrent periods of conjunctivitis, upper
      respiratory and gastrointestinal signs. Once developed, wasting and signs of CNS
      disturbances were consistent. The "effusive strain" had a 2 weeks earlier onset
      of signs and death, and a 40% outcome of effusive FIP. Mean survival times during
      the observation period were 57 +/- 26 and 57 +/- 16 (mean +/- SD in days),
      respectively. The death rates were similar in both groups. Feline coronavirus
      (FCoV) antigen was immunohistochemically detected using indirect
      immunofluorescence and was present in all kittens and in 93% of the 5
      investigated organs (lung, liver, spleen, kidney, and mesenteric lymph node).

PMID- 8266901
TI  - The occurrence of European brown hare syndrome in Finland.

PMID- 8266900
TI  - In vitro maturation of oocytes from Norwegian semi-domestic reindeer (Rangifer
      tarandus).

PMID- 8266902
TI  - Does mechanical manipulation of the reproductive organs cause a prostaglandin
      release in the heifer during embryo transfer?

PMID- 8266903
TI  - Identification of Actinobacillus pleuropneumoniae serotype 2 by monoclonal or
      polyclonal antibodies in latex agglutination tests.

PMID- 8266904
TI  - Further arguments against 4-methylimidazole as causal factor in ammoniated forage
      toxicosis: experimental seed-hay poisoning in young lambs.

PMID- 8266905
TI  - Plasma fibrinogen: levels and correlates in young adults. The Coronary Artery
      Risk Development in Young Adults (CARDIA) Study.
AB  - Sufficient evidence exists that plasma fibrinogen is a risk factor for
      cardiovascular disease to prompt a search for fibrinogen determinants. The
      authors measured fibrinogen in 4,193 participants in the Coronary Artery Risk
      Development in Young Adults (CARDIA) Study with three objectives: to describe
      fibrinogen levels in young adults, to determine if correlates of fibrinogen in
      older adults apply to younger adults, and to examine several additional
      hypothesized correlates. Fibrinogen (overall mean +/- standard deviation = 263 +/
      57 mg/dl) was greater in women than in men and in blacks than in whites; it was
      associated positively with cigarette smoking, body mass index, low density
      lipoprotein cholesterol, triglycerides, and blood pressure, and negatively with
      physical activity, high density lipoprotein cholesterol, and ethanol intake.
      Socioeconomic stress indicators and negative personality traits hypothesized as
      being associated with fibrinogen, possibly through adrenergic mechanisms, proved
      weak correlates. Parental history of diabetes was correlated positively with
      fibrinogen, in part because those with a positive parental history had greater
      body mass. Diabetes mellitus, lipoprotein(a), left ventricular mass, and oral
      contraceptive use were also positively correlated with fibrinogen concentration.
      Thus, even in young adults, fibrinogen is associated positively with most risk
      factors for atherosclerotic cardiovascular disease. This has implications for the
      role of fibrinogen as a risk factor and, potentially, for cardiovascular disease
      prevention.

PMID- 8266906
TI  - Risk factors for coronary heart disease among older men and women: a prospective
      study of community-dwelling elderly.
AB  - Data from a community-based sample of 2,812 men and women aged 65 years and over,
      living in New Haven, Connecticut, were used to examine the associations between
      blood pressure, smoking, diabetes, anginal chest pain, and relative weight and 6
      year incidence (1982-1988) of myocardial infarction and coronary heart disease
      mortality. Multivariate logistic regression analyses revealed that history of
      diabetes was associated with increased risk of incident myocardial infarction
      among women (odds ratio (OR) = 3.20; 95% confidence interval 1.46-7.01), while
      higher relative weight was a significant risk factor among men (OR = 3.46, 95%
      confidence interval 1.34-8.95 for middle vs. lowest tertile and OR = 3.24; 95%
      confidence interval 1.10-9.53 for highest versus lowest tertile). For coronary
      heart disease mortality, age and diabetes (OR = 4.47, 95% confidence interval
      1.85-10.79) were associated with increased risk among women, as was current
      smoking (OR = 3.96; 95% confidence interval 1.66-9.45). Among men, age, prevalent
      heart disease, and use of antihypertensive medication (OR = 1.84; 95% confidence
      interval 1.13-3.00) were risk factors for coronary heart disease mortality. These
      risk estimates and the relatively high prevalences of these risk factors suggest
      that attributable risks may be substantial. Observed sex differences as well as
      differences in patterns of risk factor associations for the two endpoints suggest
      that there may be different risk profiles for older men and women and for
      different coronary heart disease endpoints.

PMID- 8266907
TI  - History of lactation and breast cancer risk.
AB  - A self-administered questionnaire was completed by 1,018 women diagnosed with
      breast cancer during 1988-1989 identified through the British Columbia Cancer
      Registry and by 1,025 controls selected at random from the Provincial Voters
      List. Parous premenopausal women who had never nursed (odds ratio (OR) = 1.3, 95%
      confidence interval (CI) 0.9-2.0) or who had lactated for 1 month or less (OR =
      1.8, 95% CI 1.3-2.5) had an increased risk of breast cancer adjusted for age and
      parity, compared with women who had breast-fed 2 months or longer. The risk was
      particularly elevated (OR = 3.0, 95% CI 1.6-5.4) among women who reported having
      tried to nurse, but who were unsuccessful. Among women who nursed for at least 2
      months, there was an indication of decreasing risk with increasing duration of
      nursing. Among postmenopausal parous women, no relation between lactation history
      and breast cancer risk was evident.

PMID- 8266908
TI  - Pregnancy outcome and anti-cardiolipin antibody in women with systemic lupus
      erythematosus.
AB  - Pregnancies in women with systemic lupus erythematosus are recognized to result
      in excessive fetal morbidity and mortality. Maternal autoantibody status may
      explain some of these problems. Anti-cardiolipin antibody has been associated
      with recurrent pregnancy losses in some women with lupus, but the risk of these
      losses has not been defined. At the University of Pittsburgh between January 1,
      1979, and December 31, 1989, an unmatched case-control study design was used to
      determine whether patients with lupus and anti-cardiolipin antibody (81 cases)
      were at increased risk for adverse pregnancy outcomes in comparison with lupus
      patients without the antibody (174 controls). Cases had 98 of 192 (51%)
      pregnancies with an adverse outcome, while controls had 212 of 494 (43%). The
      odds ratio for having any adverse pregnancy outcome was 1.40 (95% confidence
      interval (CI) 0.98-1.98). When pregnancies were classified according to specific
      adverse outcome types, the frequency of late miscarriages (14-20 weeks gestation)
      in cases and controls was 8% and 3%, respectively. The odds ratio for late
      miscarriage was 2.94 (95% CI 1.31-6.60). When pregnancies were stratified by
      birth number and by occurrence of pregnancy before or after diagnosis, the
      increased frequency of late miscarriages in cases was noted only in the first
      pregnancy when the pregnancy occurred before recognized disease. Preterm births
      (before 38 weeks gestation) were increased in cases compared with controls in
      pregnancies that occurred after diagnosis for second and third pregnancies. If a
      case had one previous adverse outcome, the odds ratio for another adverse outcome
      was 3.00 (95% CI 1.62-5.57). If a case had two previous adverse outcomes, the
      odds ratio for a third adverse pregnancy outcome was 4.14 (95% CI 1.62-10.58).
      Thus, a previous adverse pregnancy outcome was the most important risk factor for
      an adverse outcome in a subsequent pregnancy.

PMID- 8266909
TI  - Perimenstrual symptom prevalence rates: an Italian-American comparison.
AB  - The purposes of this study were to determine the prevalence of perimenstrual
      symptoms among a randomly selected group of Italian women by using a standardized
      menstrual symptom instrument and to compare them with those from a census-based
      sample of free-living American women in the study by Woods et al. (Am J Public
      Health 1982;72:1257-64). Italian menstrual symptom prevalence rates were obtained
      as part of a 1984 national health screening project using the Moos Menstrual
      Distress Questionnaire translated into Italian. A total of 306 of the 426
      randomly invited women between ages 20 and 49 years participated (71.8%
      participation rate). After determination of ineligible participants (those who
      were postmenopausal, posthysterectomy, and pregnant), a total of 239 subjects
      were interviewed. Italian women reported the highest prevalence of symptoms
      during the menstrual phase and the lowest prevalence during the remainder of the
      cycle. The cross-cultural comparison indicates that, overall, Italian women
      reported higher prevalence of symptoms across the three phases of the cycle than
      did the American women, even though this difference was the smallest during the
      premenstrual phase. Prevalence rates of a number of classic premenstrual symptoms
      (e.g., breast tenderness) and affective symptoms (e.g., tension and avoid social
      activities) were found to be similar for the Italian and American samples. This
      study, while it identifies a sociocultural component to symptom reporting,
      indicates the presence of premenstrual distress symptoms in diverse cultural
      settings, even in women who are generally unaware of premenstrual syndrome. These
      findings lend support to the validity of the premenstrual phase distress
      experience and suggest the existence of the premenstrual syndrome across diverse
      cultures.

PMID- 8266910
TI  - Association of delayed conception with caffeine consumption.
AB  - This cross-sectional study investigated the relation between intake of caffeine
      containing beverages and time to conception in a population of 1,909 married
      women in New Haven, Connecticut, between May 12, 1980 and March 12, 1982. Women
      were interviewed shortly after the first prenatal visit regarding the length of
      time taken to conceive the index pregnancy, consumption of caffeine during
      pregnancy, and other exposures occurring prior to and during pregnancy. In
      logistic regression analyses, intake of caffeine from coffee, tea, and
      caffeinated soft drinks was associated with an increased risk of a delay of
      conception of 1 year or more. Compared with no caffeine use, consumption of 1-150
      mg/day of caffeine resulted in an odds ratio for delayed conception of 1.39 (95%
      confidence interval (CI) 0.90-2.13), consumption of 151-300 mg/day of caffeine
      was associated with an odds ratio of 1.88 (95% CI 1.13-3.11), and that of over
      300 mg/day (the equivalent of approximately three cups of coffee) resulted in an
      odds ratio of 2.24 (95% CI 1.06-4.73), after controlling for last method of birth
      control used, parity, and number of cigarettes per day. When the risk of
      conception for each cycle was examined using a discrete analogue of the Cox
      proportional hazards model, women who reported drinking over 300 mg/day of
      caffeine had a 27% lower chance of conceiving for each cycle, and those who
      reported drinking less than 300 mg/day had a 10% reduction in per cycle
      conception rates compared with women who consumed no caffeine. Risks for coffee,
      tea, and colas were examined simultaneously in logistic models and were found not
      to improve the fit of a model that contained a variable for total caffeine intake
      from all sources.

PMID- 8266911
TI  - Insight into the infection dynamics of the AIDS epidemic: a birth cohort analysis
      of New York City AIDS mortality.
AB  - The authors analyzed the secular trends of New York City acquired
      immunodeficiency syndrome (AIDS) mortality from 1980 through the first quarter of
      1991 using birth cohort techniques to provide insight into reasons for temporal
      changes in growth of the epidemic. By disaggregating AIDS mortality data into
      composite birth cohorts, the authors determined that the slowing in the growth of
      the epidemic is a result of a leveling or decline in AIDS deaths in male birth
      cohorts born before 1950 and a continued growth in younger male and all female
      birth cohorts. This phenomenon is believed to largely reflect earlier human
      immunodeficiency virus type 1 (HIV-1) infection patterns associated with age
      related risk behaviors; however, to some lesser extent, it could also reflect age
      related host factors or therapies that may influence the time from HIV-1
      infection to death. The findings support the hypothesis that the early infection
      dynamics of the epidemic were differentially related to age and sex, which
      resulted in a diffusion of infection from older to younger cohorts and from males
      to females over time. The future growth of the epidemic will largely depend upon
      the infection patterns of younger birth cohorts. This method of analyzing AIDS
      incidence or mortality data may contribute to a better understanding of earlier
      patterns of HIV-1 infection within a defined population, which will be useful for
      targeting prevention efforts and improving AIDS forecasting methods.

PMID- 8266912
TI  - Snippets from the past: seventy years ago in the Journal.

PMID- 8266913
TI  - Increased levels of vascular endothelial cell markers in thrombotic
      thrombocytopenic purpura.
AB  - We found that patients with thrombotic thrombocytopenic purpura (TTP) have
      significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP-D
      dimer levels, while the plasmin-alpha 2 plasmin inhibitor complex (PIC) level was
      only slightly increased. The tissue-type plasminogen activator (t-PA) level was
      increased, but it was well correlated with the plasminogen activator inhibitor-I
      (PAI-I) level. These findings suggest that hypercoagulable and hypofibrinolytic
      states coexist in these patients, in contrast to patients with disseminated
      intravascular coagulation, who exhibit coexisting hypercoagulable and
      hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as
      PAI-I, thrombomodulin (TM), and t-PA, were increased at the onset of TTP, but the
      level of von Willebrand factor (vWF) antigen was not increased. The outcome in
      TTP patients was correlated with plasma t-PA and TM levels but not with TAT or
      PIC. These results suggest that vascular endothelial cell markers, such as TM and
      t-PA, are released from injured or stimulated endothelial cells, reflecting the
      degree of vascular endothelial damage, and that the main factor in the
      pathogenesis of TTP is vascular endothelial cell injury.

PMID- 8266914
TI  - Flow cytometric analysis of changes in cytoskeletal proteins during platelet
      destruction and activation using a monoclonal antibody against platelet myosin.
AB  - We developed a new monoclonal antibody directed against platelet myosin (NNKY6
      19). Using this antibody, we analyzed platelet cytoskeletal changes related to
      stimulation with thrombin and to long-term storage. Immunoelectron microscopy
      showed increased binding of NNKY6-19 to pseudopods and the open canalicular
      system during treatment with thrombin (0.1 U/ml) and during storage for 7 days.
      Flow cytometry also showed increased binding to platelets by NNKY6-19 and an
      antiactin monoclonal antibody during storage. The binding of NNKY6-19 showed an
      increase greater than that with the antiactin antibody after storage of platelets
      for 7 days and after thrombin treatment. These findings indicated that the
      increased binding of NNKY6-19 had some relationship to changes in intracellular
      myosin and platelet morphology. Thus use of NNKY6-19 allowed analysis of subtle
      changes related to platelet activation, which differed from those detected by
      antibodies against platelet glycoproteins or by the antiactin antibody. This
      antibody appears to provide a simple method for studying changes in platelet
      cytoskeletal and surface proteins.

PMID- 8266915
TI  - Elevated plasma levels of vascular endothelial cell markers in patients with
      hypercholesterolemia.
AB  - Hypercholesterolemia is associated with an increased incidence of vascular
      complications. To assess the actual degree of activation of coagulation systems
      and vascular disorders in hypercholesterolemia, plasma levels of vascular
      endothelial cell markers, such as thrombomodulin (TM), tissue-type plasminogen
      activator, plasminogen activator inhibitor-I (PAI-I), and von Willebrand factor,
      were measured in 51 patients with hypercholesterolemia. We also investigated the
      effects of Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean
      plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA),
      TM, and PAI-I were significantly elevated in hypercholesterolemia. Of the
      hemostatic markers, only TM was significantly increased in patients with ischemic
      heart diseases (IHD). The mean concentration of total cholesterol and levels of
      TAT, FPA, PAI-I, and TM were significantly reduced after the Pravastatin
      treatment. The PIC/TAT ratio was significantly increased in non-IHD patients
      after treatment, this was not the case in IHD patients. These findings suggested
      the presence of a thrombogenic state and vascular endothelial cell disorders in
      hypercholesterolemia; such a state might well be related to hypofibrinolysis.

PMID- 8266916
TI  - Phenotypic and genotypic characterization of Hodgkin's disease.
AB  - Although a few studies have reported clonal cytogenetic changes in Hodgkin's
      disease (HD), their correlation with histologic groups is poorly defined. This is
      because of insufficient numbers of clonally abnormal cases ascertained in each of
      these studies, an inherent problem associated with the cytogenetic studies of HD.
      In this report we present results of pathologic, phenotypic, and genetic studies
      on 29 HD tumors consecutively ascertained by us and the results of a
      comprehensive analysis of the cytogenetic data available in the literature. In
      our series 75% of the tumors were positive for Epstein-Barr virus (EBV) by
      polymerase chain reaction (PCR) assay. A higher frequency of EBV-positive tumors
      showed clonal karyotypic abnormalities than the EBV-negative tumors. Unlike the
      case in the previous reports, none of the 24 tumors studied by PCR showed the
      presence of t(14;18) (q32;q21)-carrying cells. From the comprehensive analysis of
      the literature, we identified recurring nonrandom numerical changes, deletions,
      and chromosome breaks in HD. Some of these are associated either with nodular
      sclerosis or with mixed cellular histologies. A comparison of the pattern of
      these nonrandom cytogenetic changes in HD and those reported for non-Hodgkin's
      lymphomas (NHL) identified common deletions and breaks between them. These common
      genetic lesions probably play a role in disease evolution.

PMID- 8266917
TI  - Phase II trial of recombinant interferon alfa-2 in the treatment of primary
      systemic amyloidosis.
AB  - Primary systemic amyloidosis (AL) is a rare disorder characterized by production
      of an aberrant monoclonal light chain. This insoluble light chain, or a fragment
      thereof, deposits in tissues as amyloid and results in disruption of organ
      function and, ultimately, death. Although melphalan and prednisone were reported
      to benefit subsets of patients with the disease, many patients showed no benefit;
      the median survival with the disease is approximately 2 years. There is a need to
      develop new agents for patients who fail to respond to a trial of cytotoxic
      chemotherapy. A study was undertaken of interferon alfa-2 in the treatment of 15
      patients with AL because of its reported benefits in the induction and
      maintenance therapy for patients with multiple myeloma, a disease that has many
      characteristics in common with AL. None of the patients showed any objective
      regression of their disease; the median survival of the entire group was 26.3
      months. This survival is not superior to that reported with other agents used for
      this disease. We conclude that interferon alpha-2 is not a valuable agent in the
      treatment of AL.

PMID- 8266918
TI  - Combined hereditary factor XI (plasma thromboplastin antecedent) deficiency, von
      Willebrand's disease, and xeroderma pigmentosum in a Japanese family.
AB  - We report a 28-year-old-Japanese male who had a skin tumor derived from variant
      type xeroderma pigmentosum (XP), combined with factor XI (FXI) deficiency and
      type IIB von Willebrand's disease (vWd). The patient had abnormal bleeding
      history on tooth extraction. FXI clotting activity (FXI:C) and antigen (FXI:Ag)
      were remarkably decreased (< 0.01 U/ml, < 0.02 U/ml, respectively). Factor VIII
      (FVIII) clotting activity, von Willebrand factor antigen (vWf:Ag), and ristocetin
      cofactor (RCoF) were 0.43 U/ml, 45%, and 57%, respectively. Ristocetin-induced
      platelet agglutination (RIPA) revealed hyper-aggregation compared with a normal
      control. Multimeric composition of vWf in plasma showed a reduction in high
      molecular weight forms. The family study revealed two other subjects with
      homozygous hereditary FXI deficiency and vWd, and five subjects with heterozygous
      FXI deficiency. The relationship between FXI deficiency and vWd is discussed and
      previously reported cases are reviewed.

PMID- 8266919
TI  - Inversion of chromosome 16 and eosinophilia in refractory anemia with ring
      sideroblasts: report of a case.
AB  - A 72-year-old male who was admitted to our hospital with severe anemia was
      diagnosed as refractory anemia with ring sideroblasts (RARS), according to the
      French-American-British (FAB) classification of myelodysplastic syndromes (MDS).
      The patient showed persistent eosinophilia with no definite signs of either
      allergy or a parasitic infection. Chromosomal analysis of bone marrow cells
      revealed inv(16)(p13q22), a known characteristic of M4Eo acute myeloid leukemia
      (AML) in the FAB classification. This patient didn't exhibit leukemic
      transformation during his 20-month clinical course, nor was any found at autopsy.
      Therefore, this is the first case of RARS to speculate that the chromosomal
      characteristic inv(16)(p13q22) might be specific for eosinophilia rather than
      AML.

PMID- 8266920
TI  - Platelet bleeding disorder in a 30-year-old female. Mechanisms of congenital
      platelet function defects.

PMID- 8266921
TI  - Congenital acute lymphoblastic leukemia: report of a case with unusual
      immunophenotype.

PMID- 8266922
TI  - Recurrence of spinal cord compression from extramedullary hematopoiesis in
      thalassemia intermedia treated with low doses of radiotherapy.

PMID- 8266923
TI  - Effect of intravenous immunoglobulin on inhibition of fibrinogen binding to
      platelets by sera from patients with immune thrombocytopenia.
AB  - We previously described an ELISA to measure the inhibition of platelet
      glycoprotein IIb/IIIa (GPIIb/IIIa) binding to fibrinogen due to immune complexes
      and/or anti-platelet antibodies from patients with immune thrombocytopenia (ITP)
      or HIV-related ITP. Circulating immune complexes (CIC) were the main factor in
      the inhibition of GPIIb/IIIa binding to fibrinogen in HIV-related ITP, whereas in
      non-HIV ITP, inhibition was only partially due to CIC; anti-platelet antibodies
      specific to GPIIIa were also shown to play a role. In this study, we correlated
      the rise in the platelet count after intravenous immunoglobulin (IVIG) infusion
      with the decrease in inhibition of fibrinogen binding to GPIIb/IIIa by the sera
      of patients with ITP and HIV-related ITP. In the majority of the patients' sera
      tested, as the platelet count increased following the administration of IVIG, the
      degree of inhibition of GPIIb/IIIa binding to fibrinogen decreased. We also
      observed a decrease and/or disappearance of the antibodies specific to GPIIb
      and/or GPIIIa after IVIG administration. In HIV-seronegative ITP patients, the
      decrease or disappearance of anti-platelet antibodies directly correlated with
      the decreased inhibition of GPIIb/IIIa binding to fibrinogen by the 2% PEG
      supernatants of sera which contained anti-platelet antibodies. These findings
      suggest that IVIG directly affects the binding of CIC and anti-platelet
      antibodies to platelets and thereby improves platelet survival. Our results also
      suggest that the anti-idiotypic effect may contribute to IVIG's therapeutic
      action. In contrast, in the HIV-seropositive group, the decreased inhibition by
      PEG precipitates after IVIG administration was more strongly associated with an
      increase in the platelet count.

PMID- 8266924
TI  - Increased vascular endothelial cell markers in patients with disseminated
      intravascular coagulation.
AB  - We examined vascular endothelial cell markers, thrombomodulin (TM), plasminogen
      activator inhibitor-I (PAI-I), tissue plasminogen activator (t-PA), and von
      Willebrand factor, in 80 patients with disseminated intravascular coagulation
      (DIC). The levels of thrombin-antithrombin III complex (TAT), plasmin-alpha 2
      plasmin inhibitor complex (PIC) and FDP-D-dimer were significantly increased both
      before and after the onset of DIC, but were not correlated with organ failure or
      prognosis. However, the PIC/TAT ratio was lower in patients with poor prognosis
      than in those with good prognosis, and it was also lower in those with organ
      failure than in those without. Plasma TM, PAI-I, and t-PA levels were increased
      in DIC patients with organ failure or poor outcome, but were not significantly
      increased before the onset of DIC. We consider that the prognosis of patients
      with DIC might be related to organ failure or endothelial cell damage and that
      plasma levels of TM, PAI-I, and t-PA might be useful in the detection of these
      disorders and in assessing prognosis. A hypofibrinolytic state might enhance
      organ failure in patients with DIC.

PMID- 8266925
TI  - Mean platelet volume improves upon the megathrombocyte index but cannot replace
      the blood film examination in the evaluation of thrombocytopenia.
AB  - The measurement of the number of platelets larger than 3 microns (megathrombocyte
      index) is the first element in the evaluation of thrombocytopenia. This is
      currently performed by counting the number of large platelets on the peripheral
      blood film. The MPV (mean platelet volume) is an automated measurement of the
      platelet volume. This study examines the mean values, correlations, sensitivity,
      specificity and the receiver operating characteristic curve (comparison of two
      tests) to determine which of these tests better separates the production state.
      For increased vs. decreased production, the MPV was 10.0 + 1.9 fL and 8.0 + 1.5
      fL (P < .0001) respectively and the megathrombocyte index (MEGA) was 19.0 + 17.6%
      and 11.5 + 14.9% (P < .007) respectively. The correlation with the state of
      production was better for MPV (R = .47) than for MEGA (R = .20). For the MPV a
      sensitivity of 80% occurred with the MPV > or = 8.4 fL with a specificity of 71%.
      For a MEGA > or = 6%, the sensitivity was 80% but the specificity was 43%. For
      any MPV the sensitivity and specificity were better than for any MEGA. The
      Receiver Operating Characteristic Curve demonstrated that the MPV is a better
      test than the MEGA for separating the production into increased and decreased
      states. The MPV is a better test than the MEGA and will add to, but not replace,
      examination of the peripheral blood film in the diagnosis of thrombocytopenia.

PMID- 8266927
TI  - Measurement of asbestos dust levels in British asbestos factories in the 1930s.
AB  - Since the early reports of the deleterious health effects of asbestos first
      appeared in the British literature, the paucity of information on dust levels has
      been decried. Research into archival material reporting various methods of
      assessing asbestos dust levels in British factories during the 1930s indicates
      that these levels were high indeed.

PMID- 8266928
TI  - Reginald Tage: a UK asbestos prophet--a postscript.

PMID- 8266926
TI  - Hereditary thrombophilia among 217 consecutive patients with thromboembolic
      disease in Jordan.
AB  - This is a four-year prospective study on patients admitted or referred with
      thromboembolic disease to Jordan University Hospital or to the
      Thrombosis/Haemostasis Laboratory at the University of Jordan. The aim of the
      study was to find the relative prevalence of hereditary thrombophilia. For the
      purpose of this work, hereditary thrombophilia was diagnosed in the absence of an
      acquired cause of thrombophilia in addition to two of the following: 1) positive
      family history of thrombophilia, 2) confirmed same deficiency in a closely
      related family member, 3) the deficient protein is constantly below 2 SD of the
      normal mean on repeated testing. All ages were admitted to the study. Acquired
      systemic factors or local factors known to cause thrombosis or affect the levels
      of proteins opposing thrombosis were excluded. There were a total of 217 patients
      (102 males and 115 females) with confirmed thromboembolic disease. Their mean age
      was 34 years. A total of 49 patients (26 males and 23 females) fulfilled the
      criteria of hereditary thrombophilia. There were 17 cases of protein C deficiency
      (PC), 15 protein S deficiency (PS), 10 antithrombin III deficiency (ATIII), 3
      dyfibrinogenemia, 2 heparin cofactor II deficiency, and 2 plasminogen defects. In
      this group most of the thrombosis was venous. A positive family history was
      obtained in 65.3% of patients with hereditary thrombophilia. Twenty-seven
      additional relatives with deficiency were identified upon family studies. The
      calculated prevalence of hereditary thrombophilia in Jordan is put at 1/25,000.
      Screening for PC, PS, and ATIII is advocated in young patients who have
      thromboembolic disease, especially when there is a positive family history of
      thrombosis.

PMID- 8266929
TI  - Nonspecific nasal responsiveness in workers occupationally exposed to respiratory
      irritants.
AB  - The aim of the study was to establish the level of the nonspecific nasal
      responsiveness in a group of workers (N = 84) occupationally exposed to
      respiratory irritants, and to compare it with its level in healthy subjects (N =
      60). Another goal was to study the effect of occupational exposure to irritants,
      smoking, and atopy on nonspecific nasal responsiveness. The modified method of
      nonspecific nasal provocation with histamine developed by van Wijk and Dieges
      (Clin Allerg 17:563-570, 1987) was used. The method was performed by spraying
      doubling concentrations of histamine (0.03-32 mg/mL), starting with saline, in a
      cumulative manner into each nostril. The reaction was measured by total nasal
      resistance ("opening" interruption technique). The result of the test was
      expressed as provocation concentration of histamine that caused > or = 75% rise
      of total nasal resistance compared to its value measured after saline. We found a
      significantly higher percentage of nasal hyperreactors and a significantly
      greater nonspecific nasal responsiveness among 65 exposed workers (chi 2 = 78.6;
      p < 0.001, t = -5.48; p < 0.001, respectively) than in the group of healthy
      subjects. A significantly (t = 4.25; p < 0.001) increased nonspecific nasal
      responsiveness was observed during exposure when compared to nonspecific nasal
      responsiveness assessed after 2 weeks out of exposure, when tested in 19
      patients. Higher smoking rate as measured by smoking category (number of
      cigarettes multiplied with years of smoking) was associated with the lower levels
      of nonspecific nasal responsiveness. Also, we failed to confirm a relation
      between atopy and nonspecific nasal responsiveness in a group of workers exposed
      to irritants.

PMID- 8266930
TI  - Identification of formaldehyde releasers and occurrence of formaldehyde and
      formaldehyde releasers in registered chemical products.
AB  - Substances referred to as formaldehyde releasers were identified on review of the
      literature. Information on product categories and typical concentrations for
      chemical products containing formaldehyde and formaldehyde releasers was obtained
      from the Danish Product Register Data Base (PROBAS). As of February 1992, 62,000
      products were registered in PROBAS, 30,900 of these with information on
      composition and product category. Among the components of these products, 19 of
      the 22 identified formaldehyde releasers were found. The number of products
      registered with each formaldehyde releaser varied from 4 to 171, with cleaning
      agents, soaps, shampoos, paint/lacquers, and cutting fluids as the most frequent
      product categories. The most frequently registered formaldehyde releasers were
      bromonitropropanediol, bromonitrodioxane, and chloroallylhexaminium chloride.
      Formaldehyde itself was registered in 1,781 products, and was found in all
      product categories included in the study. It is concluded that products for
      industrial use as well as household and personal care products should be
      considered as sources of formaldehyde exposure. The use of unsystematic chemical
      names in literature is discussed.

PMID- 8266931
TI  - Psychometric tests for assessment of brain function after solvent exposure.
AB  - Psychometric testing is a key issue in neuropsychological toxicology assessment.
      Evaluation of methods for assessing general intellectual impairment is necessary
      as conventional neurology has been shown to be insensitive to the neurotoxic
      effects of solvents and metals. This study presents an analysis of a psychometric
      test battery from an investigation of psycho-organic syndrome in a historical
      cohort of 96 metal degreasers with long-term exposure to solvents, particularly
      trichloroethylene. The neuropsychological test battery was a combination of
      Wechsler Adult Intelligence Scale (WAIS), Luria, and tests developed in
      Scandinavia. Linear regression analysis showed a significant dose-response
      relation between increasing cumulative solvent exposure and impaired psychometric
      test performance in 9 out of 15 tests. Multivariate analysis, however, suggests
      that much of the variance was due to confounding variables, especially age, and
      to a lesser degree, primary intellectual function and word blindness. After
      control for confounding factors the strongest association with solvent exposure
      occurred for the following three tests: acoustic-motor function, Paced Auditory
      Serial Addition Test (PASAT), and the visual gestalt test.

PMID- 8266932
TI  - Mental retardation in ten-year-old children in relation to their mothers'
      employment during pregnancy.
AB  - We conducted a case-control study to examine relationships between potential risk
      factors in women's prenatal occupational histories and subsequent mental
      retardation in their 10-year-old children. Children with mental retardation
      (intelligence quotient less than 71) were identified from special education
      records maintained by the public school systems in the metropolitan Atlanta area
      and from records of various medical and social service agencies serving children
      with special needs. Control children were chosen from the rosters of 10-year-olds
      who were enrolled in regular education classes in the local public school
      systems. To obtain occupational histories, sociodemographic data, and other
      information, we interviewed 352 natural mothers (67%) of 525 case children and
      408 natural mothers (64%) of 636 control children. We computed odds ratios for
      each of 25 selected occupation, industry, and agent categories controlling for
      maternal education, birth order, and race. Most comparisons yielded odds ratios
      that were not indicative of unusual risks, but we did find lower than expected
      risks among children of teachers and health-care professionals. We also found a
      strong, positive association between mental retardation and maternal employment
      in the textile and apparel industries. The findings are useful for planning the
      direction of future studies of childhood cognitive ability to focus on specific
      parental occupations or industries.

PMID- 8266933
TI  - Agricultural work and male infertility.
AB  - Data from couples (n = 103) seeking artificial insemination with donor sperm
      because of poor sperm quality and a control group of couples treated by in-vitro
      fertilization due to female causes were analysed according to the occupations of
      the spouses. Comparison of occupational categories revealed a significant
      difference in the prevalence of agricultural occupation (11/103 vs. 1/103, p <
      0.01) between the group with male factor infertility and the normospermic
      controls. These patients also reported more long-term exposure to several
      insecticides and other pesticides. These toxic chemicals probably have a
      detrimental effect on male fertility and therefore we suggest more caution in the
      way they are handled.

PMID- 8266934
TI  - Skin contamination, airborne concentrations, and urinary metabolite excretion of
      propoxur during harvesting of flowers in greenhouses.
AB  - In eight greenhouses used for carnation culture, workers engaged in harvesting (n
      = 16), were monitored for dermal and respiratory exposure and urinary excretion
      of propoxur. Dermal exposure of hands and forearms was estimated from dislodgable
      foliar residue, using a transfer factor (a measure of transfer of pesticides from
      leaves to the skin) and the total number of working hours. Total estimated dermal
      and respiratory exposure during harvesting ranged from 0.2 to 46 mg and from 3 to
      278 micrograms, respectively. To study the relationship between external and
      internal exposure to propoxur, respiratory and dermal exposure levels were
      compared with the total amount of 2-isopropoxyphenol (IPP), the major metabolite
      of propoxur, excreted in urine in 24 hr. The Pearson correlation coefficient
      between dermal exposure and the total amount of excreted IPP was 0.95. A
      correlation coefficient of 0.84 was found between respiratory exposure and the
      amount of IPP excreted. The latter association was probably caused by the
      covariation of respiratory and dermal exposure levels (r = 0.85). Assuming
      negligible oral absorption, calculations indicated that dermal exposure could
      account for > 80% of the amount of excreted IPP. On the basis of the amount of
      IPP excreted, there was no reason to suspect increased health risks for workers
      from exposure to propoxur during harvesting.

PMID- 8266935
TI  - Prevention of epoxy resin dermatitis: failure of manufacturers to use available
      research information.
AB  - Research information is often recommended as a solution for occupational disease
      and injury. This study asks whether publicly available research information on
      prevention of a well-documented occupational hazard is acted on by an important
      sector in industry. The hazard, allergic contact dermatitis (ACD) caused by epoxy
      resins in paints, is particularly significant for painters, who may have to leave
      their jobs as a consequence of the condition. No evidence is found, according to
      a priori criteria, that paint manufacturers/suppliers acted on known prevention
      measures for epoxy resin ACD that are within their control to implement. The
      findings suggest that availability of research information alone fails to solve
      health and safety problems. Recommendations for avenues of direct and indirect
      enforcement where voluntary implementation is absent in the painting industry are
      suggested.

PMID- 8266936
TI  - Carcinogenic effects of wood dust: review and discussion.
AB  - Occupational exposure to wood dust (alone or chemically treated) is associated
      with an increased risk of developing adenocarcinoma of the nasal cavity. The
      specific causative agents, i.e., wood dust alone (natural products), wood dust
      with additives used in the processing or manufacturing of wood products, and/or
      physical determinants of wood dust and the associated risk factors, are not known
      or understood. The strongest association of exposure to wood dust and development
      of nasal cancer is observed in those occupations where workers are exposed to
      hard wood dust and chemical additives are not used. The time between first
      occupational exposure to wood dust and the development of adenocarcinoma of the
      nasal cavity averages 40 years (range 7-70 years). The epidemiological data
      available are not sufficient to make a definitive assessment between wood dust
      exposure and increased risk for cancer other than nasal cancer. The toxicity,
      mutagenicity, and carcinogenicity of wood dust to laboratory animals or in vitro
      with animal or microbial cells have not been thoroughly studied. Thus there is no
      direct experimental evidence on the potential hazards of wood dust. Data are
      insufficient or lacking on 1) wood dust exposure levels in ambient air and
      worker's breathing zone, and the deposition in the nasal cavity; 2) hard vs. soft
      wood dusts; 3) particle size and shape; 4) chemical composition of wood dust and
      the extent of contamination with chemical additives; and 5) interaction between
      inhaled wood dust, chronic irritation, and tobacco smoking. These data are
      required so that one can understand the association between wood dust exposure
      and nasal cavity tumors, along with demographic differences in cancer rates, and
      to develop strategies for intervention and reduction of disease causing agents in
      order to reduce risk to wood industry workers.

PMID- 8266937
TI  - The nose as a target for adverse effects from the environment: applying advances
      in nasal physiologic measurements and mechanisms.

PMID- 8266938
TI  - Pharmacies gain staff time as new "employee" lends a hand.

PMID- 8266939
TI  - Automated dispensing systems vary by function, location.

PMID- 8266941
TI  - Michigan pharmacies kick the habit.

PMID- 8266940
TI  - Smoking-related deaths dip slightly for first time.

PMID- 8266942
TI  - Treatment needed for national drug-abuse surveys, says GAO.

PMID- 8266943
TI  - Updated practice acts reflect current practice, provide for future growth.

PMID- 8266944
TI  - Precautions against allergic reactions to latex.

PMID- 8266945
TI  - Finding and applying for a residency position.

PMID- 8266946
TI  - Budgeting for staff pharmacists to attend educational meetings.

PMID- 8266947
TI  - How to prepare a curriculum vitae.

PMID- 8266948
TI  - Persuading old-school managers to be more democratic.

PMID- 8266949
TI  - Possible introduction of foreign matter through injection-port device.

PMID- 8266950
TI  - Compatibility of magnesium sulfate and morphine sulfate in 0.9% sodium chloride
      injection.

PMID- 8266951
TI  - Comments on study of antineoplastic drug handlers.

PMID- 8266952
TI  - Prophylaxis with aztreonam plus metronidazole during appendectomy.

PMID- 8266953
TI  - Take control of the pharmacy information system.

PMID- 8266954
TI  - Patient-focused care and pharmacy.

PMID- 8266955
TI  - Patient-focused care.
AB  - The trend away from a departmental focus and toward "patient-focused" care in
      hospitals is described; advantages of and barriers to such a change and its
      effects on pharmacy are discussed. Patient-focused care is characterized by
      decentralization of services, cross-training of personnel from different
      departments to provide basic care, interdisciplinary collaboration, various
      degrees of organizational restructuring, use of "clinical pathways"--recommended
      components of care for patients with a particular diagnosis, simplification and
      redesign of work to eliminate steps and save time (e.g., providing care according
      to predetermined protocols and charting only exceptions to the protocol), and
      increased involvement of patients in their own care. Its objectives are to use
      nonclinical and clinical staff more effectively and to improve patients'
      perceptions of the quality of care and staff members' job satisfaction. It is
      unrealistic to expect quick reductions in hospital costs through patient-focused
      care, and workers will worry about job security if an institution overemphasizes
      this aspect. A 1993 survey of 311 hospitals found that almost half had or planned
      to have patient-focused care projects. Adoption of patient-focused care projects
      may be slowed by workers' fear of new responsibilities and new reporting
      relationships. However, not all patient-focused care models involve radical
      organizational changes, and reorganizations can be such that pharmacy staff
      members are still connected to the pharmacy department even if they are
      supervised by a nonpharmacist. In some institutions patient-focused care projects
      have given pharmacy its first opportunity for decentralization.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266956
TI  - Evaluation of air quality in a sterile-drug preparation area with an electronic
      particle counter.
AB  - The air quality in a sterile-drug preparation area was assessed with an
      electronic particle counter. The numbers of airborne particles of > or = 0.5 and
      > 5 microns in a hospital i.v. room were determined. Initially, a total of seven
      sampling sites were designated; the four locations and four times with the
      highest concentrations of particles were analyzed. To determine the
      classification of the cleanroom, as described in Federal Standard 209E (FS209E),
      four equally spaced locations in the room were examined on one day. According to
      FS209E, the average concentration of particles in samples obtained at each of
      four locations uniformly spaced in a room must be < or = 100,000 per cubic foot
      of sampled air for particles of > or = 0.5 micron in order for a room to qualify
      as a Class 100,000 cleanroom. Throughout the seven-day initial study, all
      measurements of particles of > or = 0.5 micron except one yielded counts of <
      100,000/cu ft. The four highest average particle concentrations were recorded at
      1000, 1100, 1400, and 1500. Although measurement of particles of > 5 microns was
      not necessary, the measurements of these particles showed that their
      concentrations were highly dependent on staff activity. The average particle
      concentration at the four equally spaced locations was < 36,000/cu ft. At the
      four locations, the mean of the average concentrations was 29,664 particles per
      cubic foot. The upper limit of the 95% confidence interval for particle
      concentration at the four locations was 35,896/cu ft.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8266957
TI  - Preparing cytotoxic agents in an isolator.
AB  - The design of an isolator and its use by an oncology satellite pharmacy for
      preparing cytotoxic drugs are described. The isolator (Iso Concept, Boulogne,
      France) is a totally enclosed ventilated biological-safety cabinet of class III
      polyvinyl chloride (PVC) with positive air pressure, a half-suit with a rotating
      seal, and attached neoprene gloves. There are three work-stations, one for the
      half-suit and two along one side of the isolator. The ventilation and air
      filtration system consists of one entry pipe with a full ventilation-filtration
      box fitted with one prefilter, one blower, one ball valve, one high-efficiency
      particulate air (HEPA) filter, one airtight nipple connected to an automatic
      sterilizer, alarms, and one exhaust pipe protected by a HEPA filter. The air lock
      consists of a rigid, transparent Plexiglas pass-through. The chamber is
      sterilized with heated compressed air mixed with 3.5% peracetic acid. Maintenance
      includes regular changing of gloves and HEPA filters; checking of the integrity
      of the PVC, half-suit, and gloves; and washing and decontamination procedures.
      Preparation of cytotoxics is planned in advance with prescription data and
      manufacturing sheets. In the half-suit, a pharmacy technician reads the label,
      supervises preparation of the sterile admixture, and writes a label. The
      operators on the side of the unit read the manufacturing sheet and prepare the
      dose identified by the label.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266958
TI  - Fee structure for investigational drug studies.
AB  - The development and implementation of a fee structure for a pharmacy-coordinated
      investigational drug service is described. A pilot task and time study
      established specific time and cost elements for investigational drug services
      provided by the pharmacy department. To fully assess the costs in dispensing
      investigational drugs, each research study that used the investigational drug
      service was broken down into five phases of service. Each phase was further
      categorized by specific tasks or activities, and a time element to perform each
      activity or task was determined. Since some studies could require more elaborate
      randomization of patients, more extensive review of protocols, or more
      individualized dispensing procedures than others, a range of charges was derived:
      $2800 for standard protocols to $5700 for more complicated studies. An
      institutional drug therapy newsletter describing the services and costs was
      distributed to all medical staff members and principal investigators. The
      development of a fee structure for an investigational drug service coordinated by
      the pharmacy department has ensured that pharmacy services are adequately
      reimbursed and has allowed the department to allocate appropriate personnel to
      provide the services.

PMID- 8266959
TI  - Multidisciplinary task force for controlling drug expenses.
AB  - The establishment of a multidisciplinary task force to control increasing drug
      costs is described. From 1986 to 1992, dollars spent on drugs at a 964-bed
      teaching hospital increased from $9.8 million to $26.8 million, despite a tightly
      controlled formulary, prudent purchasing practices, prescribing restrictions, an
      antimicrobial order form program, a target-drug program, and an active pharmacy
      run cost intervention program. These increases occurred as a result of changes in
      the mix of drugs prescribed, increases in outpatient volume, inflation, and price
      increases resulting from the Omnibus Budget Reconciliation Act of 1990. A
      multidisciplinary task force composed of seven teams--AIDS and related issues,
      ambulatory care, medicine, obstetrics and gynecology, pediatrics, surgery, and
      systems and procedures--was formed to identify ways to reduce drug expenses and
      enhance revenue. Each team made recommendations designed to reduce the rate of
      growth of pharmaceutical expenses. To implement these recommendations, the task
      force used a variety of verbal and written strategies to educate and communicate
      with physicians, pharmacists, nurses, pharmaceutical company representatives, and
      patients. A system was developed so that goal achievement could be monitored. The
      program, which was implemented on September 16, 1991, and continued through
      September 30, 1992, reduced the growth in drug expense by $2.33 million. As a
      result of the program, control of the drug expenses became an institutional
      priority, not merely a pharmacy department priority. By establishing a
      multidisciplinary team approach involving physicians, administrators, nurses, and
      pharmacists, a substantial reduction in the growth of drug expenses can be
      achieved.

PMID- 8266960
TI  - Patient-interactive computer system for obtaining medication histories.
AB  - A portable, patient-interactive computerized system for obtaining medication
      histories is described. A comprehensive interview script modeling pharmacist
      conducted medication-history interviews was written in lay language. The script
      contains sections on demographics, current medical conditions, medication
      regimen, medication compliance, symptoms, allergy history, dietary history,
      psychosocial history, and occupational and environmental exposure; it also asks
      the patient to evaluate the system. Some of the information requested is often
      not obtained by physicians during the history and physical examination. A program
      that conducts the interview by processing a computerized version of the script
      was developed with Microsoft QuickBASIC. The program was designed to be run on a
      personal computer microprocessor so that an interview can be conducted virtually
      anywhere by using a desktop or laptop computer. Summary reports suitable for
      inclusion in the medical record are generated after each interview. Patients
      using the system took an average of 40 minutes to complete an interview. They
      entered data easily and accurately, and they gave the system a high overall
      rating. The medication-history interviewing system described produces useful,
      comprehensive, and consistent reports and requires about the same amount of time
      to conduct an interview as a human interviewer.

PMID- 8266961
TI  - Stability of an extemporaneously compounded baclofen oral liquid.
AB  - The stability of baclofen in an extemporaneously compounded oral liquid
      formulation for 35 days was studied. A suspension was prepared by grinding
      commercially available 20-mg baclofen tablets and adding Glycerin, USP, to form a
      paste. Simple Syrup, NF, was added as necessary to make a final volume of 60 mL.
      A control solution was prepared from analytical-grade baclofen powder in Simple
      Syrup, NF. The final concentration of baclofen in both formulations was 5 mg/mL.
      Three samples of each preparation were stored in 2-oz, amber glass prescription
      bottles in the dark under refrigeration at 4 degrees C. Immediately after
      preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected,
      tested for pH, and assayed in duplicate by high-performance liquid
      chromatography. On day 35, the mean percentages of the initial baclofen
      concentrations remaining were 95.9% in the suspension and 95.6% in the solution.
      The color, odor, and pH of the samples did not change appreciably over the study
      period. In an extemporaneously compounded oral liquid preparation in Simple
      Syrup, NF, stored in the dark under refrigeration, baclofen was stable for at
      least 35 days.

PMID- 8266962
TI  - Stability of octreotide acetate in polypropylene syringes.
AB  - The stability of octreotide acetate in polypropylene syringes was studied.
      Polypropylene syringes were aseptically filled with 1 mL of octreotide acetate
      0.2 mg/mL and stored at 3 or 23 degrees C under light protection or light
      exposure. Three syringes were prepared for each condition and each sampling time.
      Unopened 5-mL glass vials of the drug served as controls. Samples were removed
      immediately and at 8, 15, 22, and 29 days and analyzed by high-performance liquid
      chromatography. At 3 degrees C, octreotide stored in light-protected syringes
      maintained more than 90% of its initial concentration for up to 29 days. However,
      at 22 days the concentration in the syringes stored at that temperature and
      exposed to light was less than 90% when the standard deviation is considered. At
      23 degrees C, the drug was stable for only up to 15 days (light protection) and
      22 days (light exposure) when the standard deviation is considered. Octreotide
      acetate in polypropylene syringes was stable for up to 29 days when stored at 3
      degrees C and protected from light and for up to 22 days when stored at 23
      degrees C and exposed to light.

PMID- 8266963
TI  - Physical compatibility of melphalan with selected drugs during simulated Y-site
      administration.
AB  - The physical compatibility of melphalan injection with selected drugs during
      simulated Y-site administration was studied. A 5-mL sample of melphalan 0.1 mg/mL
      in 0.9% sodium chloride injection was combined with a 5-mL sample of each of 91
      drugs at concentrations used clinically. Each combination was prepared in
      duplicate, with the order of mixing reversed between the two. The samples were
      inspected visually in normal fluorescent light and in high-intensity light at
      zero, one, and three hours after preparation. A turbidimeter was used to measure
      the turbidity of each drug combination at the same intervals. Samples showing a
      change in the visually or turbidimetrically determined haze level were subjected
      to particle counting and sizing. None of the drug combinations resulted in visual
      evidence of precipitation, color change, or gas production. Most combinations had
      a measured turbidity of < 0.1 nephelometric turbidity unit (NTU) and were
      compatible. A few combinations had turbidities of > or = 0.1 NTU, but the
      turbidity did not change over the study period and the combinations were
      considered compatible. Combinations of melphalan with methylprednisolone sodium
      succinate, prochlorperazine edisylate, or daunorubicin hydrochloride had a very
      small increase in turbidity but were compatible. Melphalan did not increase the
      doubling of turbidity that idarubicin hydrochloride shows upon simple dilution.
      Neither the total particle burden nor the number of particles of > or = 10
      microns increased in any combination that was tested. However, combinations with
      amphotericin B or chlorpromazine hydrochloride showed large increases in measured
      turbidity and were incompatible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8266964
TI  - Stability of bupivacaine hydrochloride in polypropylene syringes.
AB  - The stability of bupivacaine hydrochloride injection 1.25 mg/mL in 0.9% sodium
      chloride injection in polypropylene syringes was studied. Plastic syringes
      containing bupivacaine hydrochloride 1.25 mg/mL in 0.9% sodium chloride injection
      or 0.9% sodium chloride injection alone were stored at 3 or 25 degrees C. A glass
      vial containing the admixture was stored at 25 degrees C as a control. For each
      condition, triplicate samples were observed immediately and 5, 11, 15, and 32
      days after preparation for precipitation and color change and analyzed for pH and
      for drug concentration by high-performance liquid chromatography. No change in
      bupivacaine concentration was observed during the 32-day study period, nor was
      there any change in color or pH nor any development of precipitation. Bupivacaine
      hydrochloride 1.25 mg/mL in 0.9% sodium chloride injection in polypropylene
      syringes was stable for up to 32 days when stored at 3 or 23 degrees C.

PMID- 8266965
TI  - Stability of fluconazole in an extemporaneously prepared oral liquid.
AB  - The stability of fluconazole in an extemporaneously prepared oral liquid was
      studied. An aqueous liquid formulation of fluconazole was prepared by
      reconstituting the powder from triturated 100-mg tablets with deionized water;
      the nominal fluconazole concentration was 1 mg/mL. Glass vials of the liquid were
      stored in the dark at 4, 23, and 45 degrees C and sampled immediately and after
      1, 2, 3, and 15 days. Samples were analyzed in duplicate for fluconazole
      concentration by high-performance liquid chromatography. The concentration of
      fluconazole was virtually unchanged under all the storage conditions. The results
      were confirmed by analysis of variance. Fluconazole 1 mg/mL in an
      extemporaneously prepared oral liquid was stable at 4, 23, and 45 degrees C for
      up to 15 days.

PMID- 8266967
TI  - Nurses' use of pharmacists' cognitive services in home care agencies in
      Mississippi.

PMID- 8266966
TI  - Provision of home infusion therapy services by U.S. hospitals in 1990.

PMID- 8266968
TI  - Physician use of a pharmacist-managed parenteral nutritional support program over
      10 years.

PMID- 8266969
TI  - High-performance liquid chromatographic determination of fentanyl and sufentanil
      returned from the operating room.

PMID- 8266970
TI  - Microwave preparation of and one-strip paper chromatography for technetium Tc 99m
      teboroxime.

PMID- 8266971
TI  - Stability of midazolam hydrochloride in 5% dextrose injection or 0.9% sodium
      chloride injection over 30 days.

PMID- 8266972
TI  - Patient injury and attempted link with pharmacist's negligence.

PMID- 8266973
TI  - ASHP technical assistance bulletin on quality assurance for pharmacy-prepared
      sterile products.

PMID- 8266974
TI  - Valuing and managing cultural diversity in the work place.

PMID- 8266975
TI  - Hemostatic abnormalities associated with monoclonal gammopathies.
AB  - To confirm and expand previous observations about the association of monoclonal
      gammopathies with hemostatic defects, a prospective evaluation was made in 42
      patients with lymphoplasmacytic disorders. The incidence of bleeding
      complications was low, despite the diversity of abnormal hemostatic tests
      observed in these patients. Patients with myeloma frequently had abnormal
      coagulation tests, including thrombin time (64%), fibrin degradation products
      (32%), platelet aggregation tests with different agonist (30% to 55%), and
      bleeding time (22%). The lack of platelet response to ristocetin and normal
      ristocetin cofactor activity in four patients with myeloma may suggest a Bernard
      Soulier-type defect. Serum viscosity was negatively correlated with platelet
      aggregation with collagen, ristocetin, and adenosine diphosphate. In patients
      with immunoglobulin myeloma, there was a positive correlation between an
      increased viscosity and a prolonged thrombin time. This study demonstrates the
      wide variety of coagulation abnormalities in lymphoplasmacytic disorders, usually
      without significant clinical implications.

PMID- 8266976
TI  - The degree of blood pressure evaluation and end organ damage with severe
      hypertension: a case-control study.
AB  - To investigate the association of blood pressure and end-organ damage in patients
      with severe hypertension in a case-controlled manner, 26 patients with syndromes
      of acute end-organ damage and severe hypertension were compared with 25 patients
      with severe but asymptomatic hypertension for a variety of demographic, clinical,
      and basic laboratory values. Differences were assessed with the Chi-square test
      and multiple logistic regression analysis. End-organ damage was significantly
      associated with a degree of systolic and diastolic blood pressure elevation, a
      history of hypertensive crisis, serum creatinine, and a history of alcohol use,
      in multivariate analysis. The relationship to creatinine and a history of
      hypertensive crisis were not present in univariate analysis. The possible
      relationships of these factors to the pathophysiology of hypertensive crisis are
      discussed.

PMID- 8266977
TI  - Chronic stimulation of atrial natriuretic peptide attenuates the secretory
      response to postural changes.
AB  - Atrial natriuretic peptide (ANP), released upon pulmonary vasoconstriction,
      modulates pulmonary vascular tone through an increase of cellular guanosine 3',5'
      cyclic monophosphate. In patients with cardiopulmonary disease, however, the
      plasma levels of ANP are relatively low, considering the high pulmonary arterial
      pressure. To evaluate the release mechanism of the hormone, plasma ANP levels
      were studied by the manipulation of right atrial stretch with different body
      postures. In healthy young subjects, the plasma ANP concentration significantly
      increased when posture changed from an upright to a supine position (p < 0.01).
      In contrast, plasma ANP concentrations were significantly higher in patients with
      chronic obstructive pulmonary disease and elderly subjects (p < 0.01), but the
      plasma levels did not increase upon the change in posture. Consistent with in
      vitro findings, the data indicate that chronic ANP stimulation attenuates the
      secretory response to acute stimuli. In addition, it was demonstrated that the
      ratio of guanosine 3',5'-cyclic monophosphate to ANP, reflecting the biologic
      effect of the hormone, was significantly lower in patients with chronic
      obstructive pulmonary disease as well as in the elderly (p < 0.05). This
      decreased biologic activity aggravated the blunted ANP response and may
      contribute to the development of pulmonary hypertension.

PMID- 8266978
TI  - Case report: intestinal infarction after an aneurysmal occlusion of superior
      mesenteric artery in a patient with Behcet's disease.
AB  - A patient with Behcet's disease, accompanied by a large aneurysm of superior
      mesenteric artery, developed an ischemic enteritis with multiple perforated
      ulcers. The ischemic necrosis of the intestine preceded by recurrent abdominal
      pain was due to an aneurysmal occlusion of superior mesenteric artery, but not
      entero-Behcet's disease. This is the first case report of intestinal infarction
      that occurred in a patient with vasculo-Behcet's disease involving the superior
      mesenteric artery. Vasculo-Behcet's disease should be included in a differential
      diagnosis of acute mesenteric artery thrombosis.

PMID- 8266979
TI  - Case report: the spectrum of autoimmune thyroid disease with urticaria.
AB  - Urticaria has many known etiologies. An association with autoimmune thyroid
      disease is described. One individual had the triad of urticaria, Hashimoto's
      thyroiditis, and rheumatoid arthritis, whereas the other individual had urticaria
      preceding Graves' disease by over 1 year.

PMID- 8266980
TI  - The role of Helicobacter pylori in acid-peptic disease.
AB  - Acid peptic disease is common, and its management is costly. Less than a decade
      ago, the traditional theories regarding the etiology and pathogenesis of acid
      peptic disease were upset by the discovery of Helicobacter pylori infection in
      association with chronic active gastritis. A substantial body of investigation
      after that discovery has established this infection as the major cause of human
      chronic active gastritis and has defined a critical role for H. pylori in the
      etiology, pathophysiology, and treatment of duodenal ulcer disease. Furthermore,
      evidence is accumulating to link H. pylori to gastric ulcers, non-ulcer
      dyspepsia, and even gastric carcinoma. Research has clarified some unique
      features of the organism that have been put to advantage in the development of
      diagnostic tests, and it has also clarified some features of the infection that
      make it difficult to treat. Although treatment is decidedly beneficial for
      certain patient subsets, simpler and more effective therapy is needed.

PMID- 8266981
TI  - Helicobacter pylori: a decade later.

PMID- 8266982
TI  - Contemporary therapy of prolactin-secreting adenomas.
AB  - Prolactin-secreting pituitary tumors are common benign pituitary neoplasm that
      cause amenorrhea, galactorrhea, and infertility. Inhibition of prolactin
      secretion by a dopamine agonist restores menses and reduces tumor size. This
      article outlines an approach to therapy and discusses the use of estrogen in
      women with prolactinomas.

PMID- 8266983
TI  - Southwestern Internal Medicine Conference: Shiga-like toxins in hemolytic-uremic
      syndrome and thrombotic thrombocytopenic purpura.
AB  - The majority of cases of hemolytic-uremic syndrome and a smaller proportion of
      cases of thrombotic thrombocytopenic purpura have recently been shown to result
      from a toxin produced by enteric bacteria, referred to as verotoxin, or Shiga
      like toxin. The predominant toxin-producing bacterial strain in North America is
      E. coli O157:H7, which causes hemorrhagic colitis in humans after ingestion of
      contaminated meat. The toxin is believed to gain entry to the circulation from
      the bowel wall; it then binds to specific glycolipid receptors abundant on renal
      vascular endothelial cells. The toxin inactivates ribosomes inside the cells,
      thereby killing them and producing the clinical manifestations of hemolytic
      uremic syndrome. Recognition of the etiology of hemolytic-uremic syndrome may
      lead to better prospects for prevention and treatment.

PMID- 8266984
TI  - Special issue: Robert J. Gorlin Festschrift.

PMID- 8266985
TI  - Sutural biology and the correlates of craniosynostosis.
AB  - The purpose of this paper is to provide a new perspective on craniosynostosis by
      correlating what is known about sutural biology with the events of
      craniosynostosis per se. A number of key points emerge from this analysis: 1)
      Sutural initiation may take place by overlapping, which results in beveled
      sutures, or by end-to-end approximation, which produces nonbeveled, end-to-end
      sutures. All end-to-end sutures occur in the midline (e.g., sagittal and metopic)
      probably because embryonic biomechanical forces on either side of the initiating
      suture tend to be equal in magnitude. A correlate appears to be that only
      synostosed sutures of the midline have pronounced bony ridging. 2) Long-term
      histologic observations of the sutural life cycle call into question the number
      of layers within sutures. The structure varies not only in different sutures, but
      also within the same suture over time. 3) Few, if any, of the many elegant
      experimental research studies in the field of sutural biology have increased our
      understanding of craniosynostosis per se. An understanding of the pathogenesis of
      craniosynostosis requires a genetic animal model with primary craniosynostosis
      and molecular techniques to understand the gene defect. This may allow insight
      into pathogenetic mechanisms involved in primary craniosynostosis. It may prove
      to be quite heterogeneous at the basic level. 4) The relationship between suture
      closure, cessation of growth, and functional demands across sutures poses
      questions about various biological relationships. Two conclusions are
      provocative. First, cessation of growth does not necessarily, or always lead to
      fusion of sutures. Second, although patent sutures aid in the growth process,
      some growth can take place after suture closure. 5) In an affected suture,
      craniosynostosis usually begins at a single point and then spreads along the
      suture. This has been shown by serial sectioning and calls into question results
      of studies in which the affected sutures are only histologically sampled. 6)
      Craniosynostosis is etiologically and pathogenetically heterogeneous. Known human
      causes are reviewed. Is craniosynostosis simply normal suture closure commencing
      too early?(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8266986
TI  - Growth pattern in the Apert syndrome.
AB  - In this paper, we demonstrate that a discernible and unique growth pattern
      characterizes the Apert syndrome. The keys to understanding Apert newborn
      measurement values are brain size and cranial configuration. Both true
      megalencephaly and coronal synostosis are present at birth. Thus, the head is
      unusually heavy and the cranium is disproportionately high. Mean newborn length
      and weight are above the normal 50th centile. Of our newborn patients, 16%
      exceeded 4,000 g in weight. Preterm infants were appropriate or slightly large
      for gestational age. A biphasic linear growth pattern was found. In childhood,
      deceleration of linear growth occurs so that most values fall between the 5th and
      50th centiles. From adolescence to adulthood, deceleration becomes more
      pronounced. This 2-step linear growth deceleration results in large measure from
      rhizomelic shortness of the lower limbs. Puberty takes place within the normal
      time frame. Although a disproportionate amount of the megalencephaly accounts for
      the dramatic increase in head height, the widely patent midline calvarial defect,
      allowing the brain to expand anteriorly into the metopic area, and some increase
      in the head breadth permit the mean head circumference at birth to normalize
      slightly above the 50th centile. During the growth period, the head circumference
      was studied in surgically unoperated Apert patients from the 1960s and earlier.
      The natural history of the growing cranium consists of gradual deceleration in
      head circumference from slightly above the 50th centile at birth to within or at 
      2 SD later on.

PMID- 8266987
TI  - Skeletal abnormalities in the Apert syndrome.
AB  - This paper reports on skeletal abnormalities in 38 patients with Apert syndrome.
      Analysis includes alterations in the shoulders, humeri, elbows, hips, knees, rib
      cage, and spine (except the cervical spine). Some patients had subacromial
      dimples and elbow dimples during infancy. Mobility at the glenohumeral joint was
      limited. Progressive limitation in abduction, forward flexion, and external
      rotation with growth was virtually a constant finding. The acromioclavicular
      joint was prominent and sometimes had an angular, pointed appearance clinically.
      This was often associated with atrophic musculature and winging of the scapulae.
      Limited elbow mobility was common and usually mild in degree. Decreased elbow
      extension was most often found with decreased flexion, pronation, and supination
      occurring less frequently. Limited elbow mobility did not change significantly
      with growth in contrast to the increasing severity observed in the shoulder
      joint. Short humeri were a constant finding beyond infancy and genua valga of
      mild degree were present in many cases. Radiographic examination strongly
      suggests that the Apert syndrome is characterized by a multiple epiphyseal
      dysplasia. We found delay in appearance of postnatal ossification centers,
      particularly in the humeral head, greater tuberosity, capitulum, and radial head.
      Subsequently, these bones became abnormal in shape. Glenoid dysplasia was
      observed consistently. The neck of the scapula was very short or absent and the
      inferior margin of the glenoid cavity was poorly demarcated from the infraglenoid
      tubercle. The humeral head became oblong in shape with relative prominence of the
      greater tuberosity which compromised abduction. In the elbow, the capitulum was
      often small and the radial head was flat in many instances.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8266988
TI  - Cytogenetic evidence that the Saethre-Chotzen gene maps to 7p21.2.
AB  - Evidence for the location of the Saethre-Chotzen acrocephalosyndactyly mutation
      on 7p21-22 is based on genetic linkage studies in families segregating for this
      autosomal dominant disorder. Linkage studies were guided by several reports of
      chromosome deletions in this region giving rise to craniosynostosis and some
      other manifestations of Saethre-Chotzen syndrome. We report on a family where a
      father and daughter carry an apparently balanced t(7;10)(p21.2;q21.2)
      translocation (de novo in the father) and have the Saethre-Chotzen syndrome.
      These observations support the localization of the Saethre-Chotzen gene to
      7p21.2.

PMID- 8266989
TI  - Saethre-Chotzen syndrome with familial translocation at chromosome 7p22.
AB  - Chromosome analysis of a male infant and his mother with Saethre-Chotzen syndrome
      demonstrated an apparently balanced translocation, t(2;7)(p23;p22). This
      association lends support to localization of the gene for Saethre-Chotzen
      syndrome to the 7p2 region and supports further involvement of gene(s) in the
      7p22 region.

PMID- 8266990
TI  - Sagittal craniosynostosis, Dandy-Walker malformation, and hydrocephalus: a unique
      multiple malformation syndrome.
AB  - The Dandy-Walker malformation and craniosynostosis have each been described as
      isolated occurrences and as components of multiple malformation syndromes. The
      purpose of this report is to delineate the characteristics of a multiple
      malformation syndrome of Dandy-Walker malformation and sagittal craniosynostosis.
      The inheritance pattern appears to be autosomal dominant.

PMID- 8266991
TI  - Proteus syndrome: clinical evidence for somatic mosaicism and selective review.
AB  - I report 2 unusual cases of Proteus syndrome that support the concept of somatic
      mosaicism. In one patient, a huge connective tissue nevus covered the chest and
      abdomen and hyperostoses of the calvaria were observed. In the other patient,
      linear verrucous epidermal nevi, epibulbar dermoids, and hyperostoses were found.
      No enlargement of the limbs or digits occurred and the plantar surfaces of the
      feet were normal. Selective aspects of Proteus syndrome not previously reviewed
      are also presented including: uncommon neoplasms; pulmonary and renal
      abnormalities; brain malformations; facial phenotype associated with seizures and
      severe mental deficiency; and types of abnormal growth in the craniofacial
      skeleton.

PMID- 8266992
TI  - Encephalocraniocutaneous lipomatosis, Proteus syndrome, and somatic mosaicism.
AB  - We report on a patient with manifestations of encephalocraniocutaneous
      lipomatosis and Proteus syndrome. Further comparison with other reported patients
      demonstrates a continuum, not 2 distinct entities that share common
      manifestations. This continuum supports the concept of somatic mosaicism.

PMID- 8266993
TI  - Compromise of the spinal canal in Proteus syndrome.
AB  - We report on 2 children with spinal stenosis and neurologic sequelae. They
      illustrate the 2 ways in which spinal compromise may develop in Proteus syndrome-
      vertebral anomalies or tumor infiltration. In one patient, spinal stenosis
      resulted from an angular kyphoscoliosis. In the other, cord compression resulted
      from infiltration of a paraspinal, intrathoracic angiolipoma.

PMID- 8266994
TI  - Acrofacial dysostoses: review and report of a previously undescribed condition:
      the autosomal or X-linked dominant Catania form of acrofacial dysostosis.
AB  - The acrofacial dysostoses (AFDs) are a heterogeneous group of disorders combining
      defects of craniofacial and limb development. The predominantly preaxial form is
      called Nager AFD, the predominantly postaxial form of AFD (POADS) is also known
      as the Genee-Wiedemann or Miller syndrome. The former appears to be about twice
      as common as the latter with well-documented autosomal dominant and recessive
      occurrences in both conditions. Only 1 AD occurrence of POADS is known, but 5
      sets of sibs are suggestive of AR inheritance. Heterogeneity of apparently
      nonsyndromal AFD of both types is powerful support for the hypothesis that the
      AFDs are polytopic field defects arising during blastogenesis. Six other
      previously described forms of AFD include the AFD syndrome of Kelly et al. (AR),
      the Rodriguez or Madrid form of AFD (AR or XLR), the Reynolds or Idaho form of
      AFD (AD), the Arens or Tel Aviv type of AFD (AF?), the presumed AR AFD syndrome
      of Richieri-Costa et al., and the AD Patterson-Stevenson-Fontaine syndrome. Here
      we review the AFDs and report on a previously apparently undescribed autosomal or
      X-linked dominant form of AFD with mental retardation in a Sicilian mother and
      her 4 sons.

PMID- 8266995
TI  - Diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia,
      and sensorineural deafness: a newly recognized autosomal recessive disorder?
AB  - We describe unrelated male and female patients with an identical syndrome of
      diaphragmatic hernia, exomphalos, hypertelorism, agenesis of the corpus callosum,
      severe sensorineural deafness, and severe myopia. One child had an iris coloboma.
      After the birth of the first affected child in each family subsequent pregnancies
      were monitored with ultrasound scan and a further affected fetus was identified
      in both families. We conclude that this constellation of anomalies represents a
      distinct, previously unreported syndrome with likely autosomal recessive
      inheritance.

PMID- 8266996
TI  - Difference in methylation patterns within the D15S9 region of chromosome 15q11-13
      in first cousins with Angelman syndrome and Prader-Willi syndrome.
AB  - Abnormalities of chromosome region 15q11-13 are associated with Angelman syndrome
      (AS) and Prader-Willi syndrome (PWS). Differences between the methylation
      patterns of the region of chromosome 15q11-13 which hybridizes to the highly
      conserved DNA, DN34, in normal individuals and in patients with AS and PWS have
      been described. We report on a family in which first cousins are affected by AS
      and PWS as a result of a familial paracentric inversion of 15q11-q13. The results
      of the studies on this family demonstrate the differences in the methylation
      patterns in the 2 conditions and the phenomenon of genomic imprinting, whereby
      genetic information is expressed differently dependent on the parent of origin.

PMID- 8266997
TI  - Rieger syndrome revisited: experimental approaches using pharmacologic and
      antisense strategies to abrogate EGF and TGF-alpha functions resulting in
      dysmorphogenesis during embryonic mouse craniofacial morphogenesis.
AB  - The major manifestations of Rieger syndrome (RS), an autosomal dominant disorder,
      include absent maxillary incisor teeth, malformations of the anterior chamber of
      the eye, and umbilical anomalies [Aarskog et al., 1983: Am J Med Genet 15:29-38;
      Gorlin et al., 1990: "Syndromes of the Head and Neck" 3rd ed.]. Linkage of RS to
      human chromosome 4q markers has been identified with tight linkage to epidermal
      growth factor (EGF) [Murray et al., 1992: Nat Genet 2:46-48]. Mutations
      associated with genes of the EGF superfamily are implicated in malformations
      arising from abnormal development of the first branchial arch [Ardinger et al.,
      1989: Am J Hum Genet 45:348-353; Sassani et al., 1993: Am J Med Genet 45:565
      569]. Down-regulation of EGF during early mouse development results in ablation
      of tooth formation [Kronmiller et al., 1991: Dev Biol 147:485-488]. Since EGF,
      TGF-alpha, and EGF receptor (EGFr) transcripts are expressed in the mouse first
      branchial arch and derivatives, experimental strategies were employed to
      investigate the consequences of down-regulation of EGF translation and inhibition
      of EGF receptor during embryonic mandibular morphogenesis. Antisense inhibition
      of EGF expression produces mandibular dysmorphogenesis with decreased tooth bud
      size; these effects are reversed by the addition of exogenous EGF to the culture
      medium [Shum et al., 1993: Development 118:903-917]. Tyrphostin RG 50864, which
      inhibits EGF receptor kinase activity, inhibits EGF or TGF-alpha stimulation of
      tyrosine phosphorylation in a concentration-dependent manner and severely retards
      mandibular development [Shum et al., 1993: Development 118:903-917].(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8266998
TI  - Cerebral malformation, seizures, hypertrichosis, distinct face, claw hands, and
      overlapping fingers in sibs of both sexes.
AB  - We report on sibs of both sexes with a multiple malformation syndrome of cerebral
      malformation, seizures, hypertrichosis, distinct face, claw hands, and
      overlapping fingers. The older boy died in a tonic extension spasm at age 4
      months. When discharged, the younger girl was 3.5 months old. This appears to be
      an autosomal recessive syndrome which to our knowledge has not been described
      before.

PMID- 8266999
TI  - Mental retardation, structural anomalies of the central nervous system,
      anophthalmia and abnormal nares: a new MCA/MR syndrome of unknown cause.
AB  - We report on 2 unrelated Brazilian girls, born to nonconsanguineous parents, and
      presenting structural central nervous system defects, hydrocephaly, macrocephaly,
      craniosynostosis, prominent forehead, anophthalmia, and abnormal nares. These
      patients may have a previously undescribed recurrent-pattern cerebro-oculo-nasal
      syndrome.

PMID- 8267000
TI  - Autosomal recessive short stature, Robin sequence, cleft mandible, pre/postaxial
      hand anomalies, and clubfeet in male patients.
AB  - We report on 2 unrelated Brazilian boys with the syndrome of autosomal recessive
      short stature, Robin sequence, cleft mandible, pre/postaxial hand anomalies, and
      clubfeet. This is the first report of male patients.

PMID- 8267001
TI  - MIDAS syndrome (microphthalmia, dermal aplasia, and sclerocornea): an X-linked
      phenotype distinct from Goltz syndrome.
AB  - Bilateral microphthalmia with blepharophimosis, linear lesions of dermal aplasia
      involving the face, and microcephaly were present in a newborn girl who died at
      age 9 months from cardiomyopathy resulting in ventricular fibrillation. Autopsy
      showed an atrial septum defect, persistent gross trabeculation of the left
      ventricle, and an arteria lusoria. This case represents a further example of a
      new entity for which we propose the term MIDAS syndrome. The acronym stands for
      microphthalmia, dermal aplasia, and sclerocornea. Our patient is the second with
      this syndrome to have a major congenital heart defect. Cytogenetic studies
      reported in previous cases indicate that the underlying gene defect can be
      assigned to Xp22.3. This new X-linked male-lethal trait should be distinguished
      from focal dermal hypoplasia that will be found to map elsewhere on the X
      chromosome.

PMID- 8267002
TI  - Johnson-McMillin syndrome: report of another family.
AB  - We describe a mother and son with facial nerve palsy, multiple truncal cafe-au
      lait spots, and mild developmental delay. The mother also had hyposmia, increased
      tendency to caries, and growth retardation, and the son hypotrichosis, hearing
      loss, and microtia. This apparently autosomal dominant disorder was described
      first by Johnson et al. [1983: Am J Med Genet 15:497-506] and Johnston et al.
      [1987: Am J Med Genet 26:925-927].

PMID- 8267003
TI  - Craniofacial anomalies, abnormal hair, camptodactyly, and caudal appendage (Teebi
      Shaltout syndrome): clinical and autopsy findings.
AB  - Teebi and Shaltout [1989: Am J Med Genet 33: 58-60] described a new syndrome of
      craniofacial anomalies, abnormal hair, camptodactyly, and caudal appendage in
      children born to a consanguineous couple. We report on a second family with the
      same pattern of anomalies occurring in a liveborn female and 3 spontaneously
      aborted fetuses, and include autopsy findings. As additional findings 2 of our
      cases had unilateral microphthalmia and kidney anomalies. Our observation
      confirms that this pattern of anomalies is a distinct syndrome with autosomal
      recessive inheritance; we suggest the synonym Teebi-Shaltout syndrome.

PMID- 8267004
TI  - Evidence for multi-site closure of the neural tube in humans.
AB  - Four separate initiation sites for neural tube (NT) fusion have been demonstrated
      recently in mice and other experimental animals. We evaluated the question of
      whether the multisite model vs. the traditional single-site model of NT closure
      provided the best explanation for neural tube defects (NTDs) in humans. Evidence
      for segmental vs. continuous NT closure was obtained by review of our recent
      clinical cases of NTDs and previous medical literature. With the multi-site NT
      closure model, we find that the majority of NTDs can be explained by failure of
      fusion of one of the closures or their contiguous neuropores. We hypothesize
      that: Anencephaly results from failure of closure 2 for meroacranium and closures
      2 and 4 for holoacranium. Spina-bifida cystica results from failure of rostral
      and/or caudal closure 1 fusion. Craniorachischisis results from failure of
      closures 2, 4, and 1. Closure 3 non-fusion is rare, presenting as a midfacial
      cleft extending from the upper lip through the frontal area ("facioschisis").
      Frontal and parietal cephaloceles occur at the sites of the junctions of the
      cranial closures 3-2 and 2-4 (the prosencephalic and mesencephalic neuropores).
      Occipital cephaloceles result from incomplete membrane fusion of closure 4. In
      humans, the most caudal NT may have a 5th closure site involving L2 to S2.
      Closure below S2 is by secondary neurulation. Evidence for multi-site NT closure
      is apparent in clinical cases of NTDs, as well as in previous epidemiological
      studies, empiric recurrence risk studies, and pathological studies. Genetic
      variations of NT closures sites occur in mice and are evident in humans, e.g.,
      familial NTDs with Sikh heritage (closure 4 and rostral 1), Meckel-Gruber
      syndrome (closure 4), and Walker-Warburg syndrome (2-4 neuropore, closure 4).
      Environmental and teratogenic exposures frequently affect specific closure sites,
      e.g., folate deficiency (closures 2, 4, and caudal 1) and valproic acid (closure
      5 and canalization). Classification of NTDs by closure site is recommended for
      all studies of NTDs in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8267005
TI  - Extension of the cleft lip phenotype: the subepithelial cleft.
AB  - We present a previously undescribed occult malformation of the upper lip manifest
      by discontinuity of the orbicularis oris muscle. The relationship of this defect
      to our current concept of abnormal maxillary process development is discussed
      along with a proposal to extend the cleft lip phenotype.

PMID- 8267006
TI  - Anthropometric craniofacial pattern profiles in Down syndrome.
AB  - A series of 21 anthropometric craniofacial measurements was performed on 199
      individuals with Down syndrome (DS), age 6 months to 61 years. These were
      compared to age and sex-matched normal standards, and Z score pattern profiles
      were constructed. These profiles confirmed brachycephaly and reduced ear length.
      With increasing age, maxillary growth was reduced in comparison to mandibular
      growth. Clinically, this was manifested by a change in facial shape from the
      characteristic round face of infancy to an oval shape in later life. Stepwise
      forward discriminant function analysis identified a subset of three variables
      (ear length, maxillary arc, and upper facial depth) which could accurately
      classify greater than 99% of the individuals in the combined sample of affected
      and unaffected individuals. Of the subjects with DS, 96.8% were classified
      correctly. These findings demonstrate the usefulness of anthropometric
      craniofacial pattern profiles in defining abnormal facial dimensions in
      particular syndromes and documenting the changes that occur with age. The
      technique should facilitate syndrome recognition, identification of carriers, and
      comparisons between syndromes.

PMID- 8267007
TI  - Cranial base and face in mandibulofacial dysostosis.
AB  - Using longitudinal roentgencephalometry, we studied craniofacial growth in two
      children with mandibulofacial dysostosis. In one child, data were supplemented by
      three-dimensional reconstructions of CT scans and stereolithographic models of
      the craniofacial skeleton. Progressive basilar kyphosis was found in both
      children, the hypothesized caused being bending of the cranial base at the level
      of the sphenofrontal suture. Such bending acting in concert with abnormal growth
      of the mandible led to impairment of the airway. We advocate careful monitoring
      of craniofacial growth and respiratory function in mandibulofacial dysostosis
      from birth through adolescence.

PMID- 8267008
TI  - Lingua cochlearis in multiple pterygium syndrome.

PMID- 8267009
TI  - Lingual lesions and liabilities.

PMID- 8267010
TI  - Angel-shaped phalango-epiphyseal dysplasia (ASPED): identification of a new
      genetic bone marker.
AB  - We describe a "new" mild malformation of the phalanx, which we call the "angel
      shaped phalanx" (ASP) because of its resemblance to the little angels used for
      the decoration of Christmas trees. A particular middle phalangeal type of ASPs is
      found in a distinct variety of multiple epiphyseal dysplasia with marked
      retardation of bone age and severe coxarthrosis in adult life, previously
      reported as "hereditary peripheral dysostosis" [Bachman, 1967: Proc R Soc Med
      60:21-22; Giedion, 1969: Fortschr Rontgenstr 110:507-524]. However, these authors
      overlooked the unique configuration of the middle phalanges. We renamed the
      condition "angel-shaped phalango-epiphyseal dysplasia (ASPED)", which may be
      transmitted in an autosomal-dominant manner. Six new patients are added, bringing
      the total to nine patients (two families and two isolated patients). ASPs were
      seen in five of six children. The ASPs grew into inconspicuous brachydactyly
      after physeal closure (3/3). The most important additional radiological finding
      is late and dysplastic development of both femoral heads (5/5), leading to
      Perthes-like and osteoarthritic changes and severe hip pain in the early thirties
      (2/2 adults, having reached this age). The marked retardation of carpal bone age
      may lead to unnecessary clinical evaluation for endocrine disorders. Less
      frequent clinical manifestations of ASPED are hyperextensibility of the
      interphalangeal joints (7/9) and hypodontia (4/7). Other types of ASPs are
      observed in brachyphalangy type C, spondylo-megepiphyseal-metaphyseal dysplasia,
      and other conditions. The concept of mild bone abnormalities as specific markers
      for genetic disease, as with cone-shaped epiphyses and now evident in ASPED, may
      also be useful for ASPs in general.

PMID- 8267011
TI  - Patient with double heterozygosity for achondroplasia and pseudoachondroplasia,
      with comments on these conditions and the relationship between
      pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.
AB  - We present a 7 1/2-year-old girl with achondroplasia and pseudoachondroplasia.
      Her mother has achondroplasia and her father has pseudoachondroplasia.
      Radiographic manifestations of these two conditions from infancy to age 6 years
      are outlined. The findings in this patient are compared with those of
      achondroplastic patients and pseudoachondroplastic patients of similar ages. Our
      review of radiographs of many pseudoachondroplastic patients and subsequently of
      those of patients with multiple epiphyseal dysplasia (MED), Fairbank type,
      reinforced our opinion that pseudoachondroplasia and multiple epiphyseal
      dysplasia, Fairbank type, are closely related conditions. MED, Fairbank type, may
      be the mildest form of pseudoachondroplasia. Recently published electron
      microscopic findings also suggest this.

PMID- 8267012
TI  - Short rib-polydactyly syndrome (SRPS) with anencephaly and other central nervous
      system anomalies: a new type of SRPS or a more severe expression of a known SRPS
      entity?
AB  - We describe two patients with short rib-polydactyly syndrome (SRPS) from two
      unrelated Spanish families. These patients present clinical and radiological
      characteristics that overlap those of the different established types of SRPS. In
      addition, one patient had anencephaly and the other patient had severe brain
      abnormalities with a family history of an older sister with anencephaly, and a
      brother diagnosed with SRPS. This second family is interesting in that the two
      affected brothers present with different clinical and radiological findings; for
      example, one had ovoid tibiae and the other did not. This particular family shows
      that intrafamiliar variation is also observed within SRPS. It remains unsettled
      whether these cases might be considered a new type of SRPS or a variant of an
      established entity or whether the differences between the SRPS represent
      variability or heterogeneity. Molecular studies may answer this question in the
      near future.

PMID- 8267013
TI  - Mesomelic limb shortness: a previously unreported autosomal recessive type.
AB  - We report on sibs, the offspring of a consanguineous mating, whose mesomelic
      shortness and bowing of limbs with associated skin dimpling, retrognathia,
      mandibular hypoplasia, cleft palate, and camptodactyly represents a previously
      apparently unreported syndrome. The radiological findings are discussed,
      particularly with regard to the main known diagnostic possibilities.

PMID- 8267014
TI  - Schimke immuno-osseous dysplasia: case report and review.
AB  - We report on a patient with Schimke immunoosseous dysplasia, an autosomal
      recessive disorder, and review nine patients from the literature. Manifestations
      include spondyloepiphyseal dysplasia, lymphopenia, signs of defective cellular
      immunity, and progressive renal disease. This is the first patient known to have
      the additional findings of thrombocytopenia and microdontia.

PMID- 8267015
TI  - Provisionally unique autosomal recessive chondrodysplasia punctata syndrome.
AB  - Stippled epiphyses occur in several monogenic, teratogenic, or aneuploidy
      syndromes. We describe two sibs with a provisionally unique chondrodysplasia
      punctata syndrome, who have, in addition to stippled epiphyses, minor facial
      anomalies, short stature, and ocular colobomata. Inheritance of this condition is
      likely autosomal recessive.

PMID- 8267016
TI  - Cognitive skills in achondroplasia.
AB  - Increased intracranial pressure and ventricular and subarachnoidal dilatation are
      common manifestations in achondroplasia. They rarely lead to major neurologic
      and/or psychomotor deficits and neurosurgical intervention is seldom needed. The
      present study was undertaken to detect signs of minor cerebral dysfunction and
      discuss possibilities of their prevention. Thirty children with achondroplasia
      were compared to 3 control groups: their next-born sibs, 30 children with other
      forms of dwarfism, and 30 children with normal height. Early development was
      assessed by means of questionnaires. Cognitive skills were evaluated with the
      German version of the Cognitive Abilities Test and the Lorge-Thorndike
      Intelligence Test. Personality data were tested using standardized neuroticism,
      extraversion, and anxiety scales. Children with achondroplasia had more frequent
      histories of delayed motor development, retarded speech development, and lower
      school grades in language-related specialties. Psychometric testing disclosed
      total and subtest scores in the population-based normal range. In comparison with
      their sibs and matched controls children with achondroplasia had significantly
      lower total scores mainly caused by low scores in the subtest "verbal
      comprehension." We conclude that verbal comprehension is significantly impaired
      in children with achondroplasia. This partial deficiency is probably related to
      frequent middle ear infections and resulting conductive hearing loss. Hypotonia
      with delayed oropharyngeal muscle coordination and parental response to an
      altered, more infantile instinctive releasing pattern may be contributing
      factors.

PMID- 8267017
TI  - Historical case of dwarfism: attempted diagnosis.
AB  - A brief description is given of a male dwarf painted by the Italian artist Geromo
      Induno in 1852. This portrayal seems not to have been mentioned previously in the
      medical literature. Several experts were consulted in an attempt to diagnose the
      underlying skeletal dysplasia. Most opted for pseudoachondroplasia, with the most
      detailed argument coming from the subject of this Festschrift.

PMID- 8267018
TI  - Loin pain hematuria syndrome.
AB  - LPHS is a disorder of obscure etiology and inconsistent pathology whose most
      prominent clinical feature is severe flank pain. Were it not for the hematuria
      which nearly always accompanies the pain, there would be no specific objective
      correlate of the syndrome. In this sense, it is similar to a number of chronic
      conditions which have inspired heated controversy about their very existence as
      discrete diseases. As the foregoing discussion of pathogenesis, pathology and
      diagnosis illustrates, with respect to two important characteristics of a
      'prototypical' disease--specificity and mechanism--LPHS falls far short. This,
      coupled with a rather unimpressive 'visible' concomitant of the symptoms
      (hematuria), has inspired skepticism and even suspicion in some physicians
      confronted with the demands for analgesia by these patients. On the part of
      physicians who have been involved in the care of these patients over time,
      however, there is no doubt that they suffer from a bona fide illness, if not a
      disease. The severity of the illness is evinced by the rather extreme measures
      that have been taken in its treatment; e.g., surgical denervation of the kidney,
      nephrectomy, autotransplantation. Only the last of these appears to offer the
      hope of enduring pain relief while preserving renal function, but the risk of
      pain recurrence in the autograft may limit the usefulness of this procedure.
      Accordingly, narcotic analgesics may need to be the treatment of first and last
      resort. Development of specific treatment will depend upon elucidating the
      pathogenesis of the disorder. The available data suggest further investigation of
      the role of vasoactive mediators, and the coagulation and immune systems.

PMID- 8267019
TI  - Serum and erythrocyte tocopherol in uremic patients: effect of hemodialysis
      versus peritoneal dialysis.
AB  - alpha-Tocopherol is transferred from serum to erythrocytes by high-density
      lipoproteins (HDL). We have studied total serum, HDL and erythrocyte tocopherol
      concentration in uremic patients on hemodialysis (HD; n = 18) and continuous
      ambulatory peritoneal dialysis (CAPD; n = 14), and the relationship between HDL
      and erythrocyte tocopherol content. Serum and erythrocyte tocopherol were
      determined by high-performance liquid chromatography. Serum tocopherol levels
      were higher in CAPD patients (p < 0.05) than in control (n = 30) and HD groups.
      Erythrocyte tocopherol was lower in HD patients than in the controls but there
      were no differences between CAPD patients and the control group. Bioavailable
      tocopherol was found to be normal in both HD and CAPD patients. HDL-tocopherol
      was lower in both HD and CAPD groups, but probably enough to reach a normal level
      of tocopherol in erythrocytes, as has been demonstrated in CAPD patients. So,
      although a defect in the transfer of tocopherol to red blood cells is possible,
      some other causes could influence it too, as a greater antioxidant consumption in
      HD patients.

PMID- 8267020
TI  - Soluble interleukin-2 receptors and beta 2-microglobulin in patients with primary
      glomerulonephritis.
AB  - Serum levels of soluble interleukin-2 receptors (IL2R) and of beta 2
      microglobulin (beta 2M) were studied with the immunoenzymatic technique in 38
      patients with primary glomerulonephritis (GN), in 10 patients with essential
      hypertension (EH) and in 30 healthy subjects. IL2R correlated with beta 2M (p <
      0.05). IL2R and beta 2M were higher in patients with GN (p < 0.003, p < 0.001,
      respectively) and in patients with EH (p < 0.003, p < 0.01, respectively) than in
      healthy subjects. IL2R and beta 2M correlated with serum creatinine, but not with
      proteinuria. Our data would suggest the existence of lymphocyte activation in
      patients with GN. Only speculations can be advanced with regard to the observed
      increase in these parameters in EH patients.

PMID- 8267021
TI  - Scintigraphic evaluation of the short- and long-term renal effects of oral
      felodipine using technetium-99m-mercaptoacetyl triglycine.
AB  - The short- and long-term effect of felodipine on renal perfusion and tubular
      function was investigated using a new renal tubular imaging agent, 99mTc
      mercaptoacetyl triglycine (99mTc-MAG3). Twelve patients with essential
      hypertension (mean age = 49 +/- 8 years) were studied. Renal scintigraphies with
      180 MBq 99mTc-MAG3 were performed at baseline, at the 2nd hour following oral
      administration of 5 mg felodipine and 4 weeks later on 5-10 mg daily felodipine
      therapy. The time-activity curves of each kidney were obtained following
      background subtraction. The 99mTc-MAG3 clearance value was measured for each
      kidney. In addition, perfusion index (PI), reno index, time to maximum, half
      maximum and two thirds of maximum activity values of each kidney were calculated.
      Systolic and diastolic blood pressures were significantly lowered with long-term
      administration of felodipine (from 159 +/- 12/105 +/- 5 to 141 +/- 11/87 +/- 7 mm
      Hg, p = 0.01 and p = 0.002, respectively). Heart rate did not change
      significantly. Initially, a decrease in PI indicating an increase in renal blood
      flow (from 246 +/- 96 to 194 +/- 54, p = 0.01) was observed, whereas no change
      was noted during the chronic administration (to 230 +/- 69, p = NS). Total
      clearance of 99mTc-MAG3 was decreased nonsignificantly following the initial dose
      of felodipine (from 361 +/- 93 to 351 +/- 91 ml/min, p = NS). During long-term
      therapy, felodipine did not alter the perfusion and tubular function of the
      kidneys. Our results indicated that felodipine causes a significant increase in
      renal blood flow initially, even with a nonsignificant change in systemic blood
      pressure.

PMID- 8267022
TI  - Renal function in neonatal hyperbilirubinemia.
AB  - A total of 75 jaundiced infants with gestational ages ranging from 37 to 42 weeks
      were studied during the first 10 days of age to evaluate renal function by
      measuring endogenous creatinine clearance (Ccr), fractional excretion of N-acetyl
      beta-D-glucosaminidase (NAG) to creatinine, fractional excretion of sodium (FENa)
      and urine osmolality. All jaundiced infants were divided into two groups. Group 1
      infants (n = 35) had total serum bilirubin levels ranging between 21 and 39.6
      mg/dl (mean 27.2). Exchange transfusions were performed in all group 1 infants at
      the time of the initial study. Group 2 infants (n = 40), whose total serum
      bilirubin levels ranged between 12.3 and 20 mg/dl (mean 16.4), received
      phototherapy, except for 2. Conjugated bilirubin levels were less than 1.0 mg/dl
      in all these infants. Results were compared with 25 untreated control infants
      with corresponding gestational and postnatal ages. Follow-up studies were done in
      27 of the 35 group 1 infants and in 32 of the 40 group 2 infants prior to
      hospital discharge, when total serum bilirubin levels had decreased to less than
      10 mg/dl. Ccr, fractional excretion of NAG to creatinine, FENa and urine
      osmolality of group 1 infants were statistically significantly different when
      compared to those of group 2 and the control infants. The measured parameters in
      the post-treatment follow-up study of group 1 infants returned to near-normal
      levels when total serum bilirubin levels became normal. However, no significant
      differences were seen between group 2 and the control infants in any of the
      measured parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267023
TI  - Treatment of acute hypernatremia with hemodialysis.
AB  - The prognosis of severe hypernatremia in the adult is dismal, and new approaches
      are needed to improve this situation. Here we describe 3 cases of patients with
      severe hypernatremia (sodium levels of 178, 172, 182 mEq/l) associated with
      cardiopulmonary or hepatorenal complications that were treated successfully with
      acute hypotonic hemodialysis (dialysate sodium 110 mEq/l). We provide information
      of our investigational protocol since the past literature has dealt mostly with
      peritoneal dialysis. Our preliminary experience has yielded adequate results
      without significant side effects, but additional studies are needed to refine
      this technique that might be life-saving in selective situations.

PMID- 8267024
TI  - Increased norepinephrine secretion in patients with the nephrotic syndrome and
      normal glomerular filtration rates: evidence for primary sympathetic activation.
AB  - Considerable controversy exists in regard to the state of arterial circulatory
      integrity in patients with the nephrotic syndrome. Increased sympathetic nervous
      system activity, along with activation of the renin-angiotensin-aldosterone
      system and the nonosmotic release of vasopressin, is seen in other states of
      arterial underfilling. Thus, in the present study, sympathetic nervous system
      activity was assessed by determining plasma norepinephrine secretion and
      clearance rates using a whole-body steady-state radionuclide tracer method in 6
      edematous patients with the nephrotic syndrome of various parenchymal etiologies
      and 6 normal control subjects in the supine position. Patients were withdrawn
      from all medications 7 days prior to study. Mean creatinine clearances and serum
      creatinine concentrations were normal in both the nephrotic syndrome patients and
      controls (99 +/- 13 vs. 112 +/- 15 ml/min, p = NS, 1.1 +/- 0.1 vs. 0.8 +/- 0.0
      mg/dl, p = 0.03, respectively). However, the nephrotic syndrome patients
      exhibited significant hypoalbuminemia (2.0 +/- 0.4 vs. 3.8 +/- 0.1 g/dl, p <
      0.01). The supine plasma norepinephrine level was elevated in the patients with
      the nephrotic syndrome as compared with controls (240 +/- 58 vs. 119 +/- 22
      pg/ml, p = 0.07). More significantly, the secretion rate of norepinephrine was
      markedly increased in nephrotic patients (0.30 +/- 0.07 vs. 0.13 +/- 0.02
      micrograms/m2/min, p < 0.05), whereas the clearance rate of norepinephrine was
      similar in the two groups (2.60 +/- 0.29 vs. 2.26 +/- 0.27 l/min, p = NS). Plasma
      renin activity and plasma aldosterone, arginine vasopressin and atrial
      natriuretic peptide concentrations were not different in nephrotic syndrome
      patients compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267025
TI  - Glomerulonephritis with various crystalline deposits.
AB  - A 60-year-old Japanese male was admitted with nephrotic syndrome complaining of
      facial and pedal edema. Renal biopsy revealed mesangial and endocapillary
      proliferation with massive mesangial and subendothelial deposits. Deposits of
      IgA, IgG, IgM, C3 and fibrinogen were identified by immunofluorescence technique
      in both mesangial and subendothelial areas. Deposits of kappa and lambda light
      chains were also recognized in similar patterns. Electron microscopy revealed
      crystalline structures of various appearance in these deposits. A large deposit
      consisted of various small triangular, quadrilateral and polygonal shapes of
      deposits with crystalline structures. These crystalline structures exhibited
      lattice or parallel lamellar lines with different periodic distances. Although a
      disease producing paraproteinemia was suspected, no immunoglobulin disorder or
      light chain abnormality could be detected on clinical and laboratory
      examinations. On the second biopsy, a faint reaction for cryoglobulin was
      recognized. However, the crystalline deposits observed in this case were
      absolutely different from the tubular structures seen in cryoglobulinemic
      nephropathy. This was a very rare and unclassified case.

PMID- 8267026
TI  - Hypercalcemia associated with Wegener's granulomatosis and hyperparathyroidism:
      etiology and management.
AB  - We report a case of hypercalcemia in a patient with coexisting
      hyperparathyroidism and Wegener's granulomatosis. Parathyroidectomy with removal
      of an adenoma resulted in a low parathyroid hormone level but high calcitriol
      levels and hypercalcemia persisted. In various granulomatous diseases,
      hypercalcemia has been shown to be the result of overproduction of 1,25-dihydroxy
      vitamin D by disease-activated macrophages. Chloroquine has been demonstrated to
      effectively reduce the extrarenal synthesis of 1,25-dihydroxyvitamin D and serum
      calcium concentration in hypercalcemic patients with sarcoidosis. Hypothesizing
      that a similar mechanism would explain hypercalcemia in Wegener's granulomatosis
      as well, a therapeutic trial of chloroquine was initiated. The patient responded
      to chloroquine 500 mg twice daily with significant decreases in serum 1,25
      dihydroxyvitamin D and calcium levels. This report extends previous observations
      of hypercalcemia associated with other granulomatous diseases to Wegener's
      granulomatosis and demonstrates an effective reduction of serum calcitriol and
      calcium levels in response to chloroquine therapy.

PMID- 8267027
TI  - Bacteremia complicating peritonitis in peritoneal dialysis patients.
AB  - Bacteremia is a rare complication of peritonitis in end-stage renal failure
      (ESRF) patients treated by peritoneal dialysis. Three of our ESRF patients on
      peritoneal dialysis developed bacteremia during a peritonitis episode (1/19
      peritonitis episodes). In 2 cases, the responsible organism was Escherichia coli
      and peritonitis was most likely associated with infection of the biliary tract.
      The 3rd patient had a perforation of the colon and Klebsiella spp. was the
      infective organism. Only the last patient survived but had to be transferred to
      hemodialysis. Bacteremia during peritonitis is infrequent in peritoneal dialysis
      patients and it appears to be related to other intra-abdominal events.

PMID- 8267028
TI  - Renin-dependent renal parenchymatous hypertension detected by angiotensin
      converting enzyme inhibitor renography.
AB  - Hypertension secondary to an activated renin-angiotensin system without renal
      artery stenosis can be detected by angiotensin-converting enzyme (ACE) inhibitor
      renography. Two cases of renin-mediated hypertension without major or branch
      vessel stenosis supplying the kidney with parenchymatous disease were discovered
      by ACE inhibitor renography.

PMID- 8267029
TI  - Penicillamine-induced rapidly progressive glomerulonephritis in a patient with
      rheumatoid arthritis.
AB  - A 67-year-old woman with rheumatoid arthritis presented rapidly progressive
      glomerulonephritis (RPGN) after 5 months of D-penicillamine (250 mg/day)
      treatment. Light microscopy study showed severe glomerulonephritis with crescent
      formation in 60% of the glomeruli and infiltration of inflammatory cells in the
      wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3
      deposits along the capillary walls and mesangium. The patient was treated with
      steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A
      complete recovery of renal function was achieved in a few weeks. This new case of
      RPGN in the course of D-penicillamine treatment emphasizes the need for frequent
      monitoring of renal function and evaluation of urinary sediment and proteinuria
      in these patients. The prompt discontinuation of D-penicillamine and vigorous
      treatment measures could allow for a good prognosis as in this case.

PMID- 8267030
TI  - Plasma exchange in the treatment of early recurrent focal glomerulosclerosis
      after renal transplantation. Report and review.
AB  - We report a 29-year-old female with recurrent focal glomerulosclerosis (FGS)
      presenting as heavy proteinuria immediately following renal transplantation. From
      day 13 after transplantation, daily plasma exchange was performed 6 times.
      Proteinuria decreased from 13 to 0.2 g/day after plasma exchange and remained to
      be less than 0.1 g/day even 20 months thereafter. Our review of the literature on
      the use of plasma exchange in treating recurrent FGS suggests this procedure is
      not useful in patients whose allograft biopsy showed advanced glomerular
      sclerotic lesions. We propose early plasma exchange may be a therapeutic option
      in those patients who have no sclerotic lesions in their allograft biopsy.

PMID- 8267031
TI  - Early history of renal rickets.
AB  - The first reports of renal osteodystrophy came from Europe in the late 19th
      century. A case report by Davies Colley in 1883 probably represented the first
      ever description of renal rickets. Although these reports were mostly descriptive
      with little or no discussion of the pathophysiological relationship, some of the
      recommendations for treatment were amazingly insightful and would still be valid
      by today's standards. The significance of dietary protein/phosphate restriction
      with vitamin D supplementation was already emphasized in these early days.
      Studies into the pathophysiology of renal rickets started in the early 20th
      century. A summary of the literature in the understanding of renal rickets is
      provided up to the 1940s.

PMID- 8267032
TI  - Reasonable positive predictive values of captopril renography in renovascular
      hypertension.

PMID- 8267033
TI  - Early pregnancy changes in hemodynamics and volume homeostasis are consecutive
      adjustments triggered by a primary fall in systemic vascular tone.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that early
      pregnancy changes in volume homeostasis develop as a consequence of preceding
      changes in maternal hemodynamics. STUDY DESIGN: Maternal cardiovascular function
      of 10 pregnant women was followed up by Doppler echocardiography. Vascular
      filling state and volume homeostasis were evaluated by echocardiographic index
      values, glomerular filtration rate, serum osmolality, and volume-regulating
      hormones. Studies were performed weekly in early pregnancy, in the second and
      third trimesters, and post partum. Changes relative to the fifth week and the
      consistency of changes between weeks 5 and 8 were evaluated by nonparametric
      statistics. RESULTS: In early pregnancy cardiac output increased and afterload
      decreased. Concomitant increases in ultrasonic preload index values and
      glomerular filtration rate were accompanied by decreases in serum renin, Na+, and
      osmolality. CONCLUSION: These data support the concept that maternal hemodynamic
      adaptation to pregnancy is most likely triggered by a primary fall in systemic
      vascular tone. The resulting rapid fall in preload and afterload leads to a
      compensatory increase in heart rate and activation of the volume-restoring
      mechanisms. Subsequently cardiac output increases because of a rise in stroke
      volume, which develops because the vascular filling state normalizes, whereas the
      reduced afterload reduction is maintained.

PMID- 8267034
TI  - Longitudinal quantitation of middle cerebral artery blood flow in normal human
      fetuses.
AB  - OBJECTIVES: We attempted to quantify noninvasively blood flow of the middle
      cerebral artery in human fetuses during five distinct periods. STUDY DESIGN:
      Twenty normal fetuses had color pulsed Doppler ultrasonography of the middle
      cerebral artery. A total of 68 studies were successfully done and are reported.
      The Doppler sample was placed as parallel to the direction of the vessel flow as
      possible. All waveforms were recorded on a strip chart at a preset speed of 100
      mm/sec. Six Doppler waveforms were digitized for the time velocity integral (area
      under the curve is equal to time velocity integral) and averaged. Middle cerebral
      blood flow was obtained by multiplying the time velocity integral of the Doppler
      curve by the cross-sectional area of the vessel. The combined cardiac output was
      obtained by adding the right and left ventricular outputs, which were obtained by
      multiplying the time velocity integrals by the area of the corresponding annuli.
      Analysis of variance for repeated measurements was used to determine
      significance. RESULTS: The diameter of the middle cerebral artery, the time
      velocity integral, and the peak flow velocity of the Doppler waveform increased
      significantly with advancing gestational age. Blood flow to the middle cerebral
      artery ranged from 23 ml/min at 19 weeks to 133 ml/min at term. Resistivity index
      values were not correlated with advancing gestational age. The percent of the
      cardiac output to one of the two middle cerebral arteries remained constant
      throughout gestation with a range between 3% and 7%. CONCLUSIONS: (1) Time
      velocity integral, peak flow velocity, diameter, and blood flow of the middle
      cerebral artery increased significantly with gestational age; (2) the percent of
      the total cardiac output to the middle cerebral artery does not significantly
      change with gestational age.

PMID- 8267035
TI  - Quantitative assessment of human fetal renal blood flow.
AB  - OBJECTIVE: Our purpose was to longitudinally quantify human fetal renal blood
      flow. STUDY DESIGN: Twenty-two normal fetuses underwent a color-pulsed Doppler
      evaluation of the renal artery. The Doppler waveforms were digitized to assess
      the velocity-time integral. The size of the vessel was determined during systole
      with color high-resolution two-dimensional ultrasonography. Renal blood flow was
      estimated by multiplying the time-velocity integral (i.e., area under the curve)
      by the area of the renal artery. The combined cardiac output was calculated by
      adding right and left inflow Doppler-derived volumes. RESULTS: Renal artery size,
      peak flow velocity, time-velocity integral, and renal blood flow significantly
      increased with advancing gestational age. The resistivity indexes, such as the
      systolic/diastolic ratio or the Pourcelot index of the fetal renal artery, did
      not significantly change with advancing gestational age. The pulsatility index,
      however, was correlated with gestational age. The percentage of the combined
      cardiac output to the fetal kidney remained constant throughout gestation.
      CONCLUSIONS: Color pulsed Doppler can be used to visualize small and deep
      vascular structures in the human fetus. Renal blood flow increased with advancing
      gestational age. This increase seems to be related to the increase in the
      combined cardiac output.

PMID- 8267036
TI  - The effect of immunoglobulin G fractions from patients with lupus anticoagulant
      on placental prostacyclin and thromboxane production.
AB  - OBJECTIVE: We evaluated whether the production of prostacyclin and thromboxane by
      normal human placental tissue is consistently altered by incubation with
      immunoglobulin G fractions prepared from plasma of patients with lupus
      anticoagulant. STUDY DESIGN: The immunoglobulin G fractions were prepared from
      eight patients with lupus anticoagulant and eight control patients. Doses of
      these fractions (3 mg, 7.5 mg, and 12 mg) were incubated with placental explants
      obtained from normal pregnancies, and prostacyclin and thromboxane production was
      assessed over 48 hours. RESULTS: Prostacyclin production was similar for
      placental tissue incubated with immunoglobulin fractions from control and lupus
      anticoagulant patients at all of the doses tested. Placental production of
      thromboxane was significantly increased with immunoglobulin fractions from lupus
      anticoagulant patients for all three doses (p = 0.02). CONCLUSIONS: The
      immunoglobulin G fraction from patients with lupus anticoagulant consistently
      alters placental thromboxane production without affecting prostacyclin
      production. Increases in placental thromboxane production may contribute to
      antiphospholipid antibody-mediated pregnancy loss.

PMID- 8267037
TI  - Effects of intrapartum stress on fetal adrenal function.
AB  - OBJECTIVE: Our purpose was to characterize the fetal adrenal response to acute
      intrapartum stress in otherwise uncomplicated pregnancies. STUDY DESIGN: Term
      infants (n = 61) diagnosed as having fetal distress during labor, as indicated by
      heart rate abnormalities, and delivered of women having normal pregnancies were
      pair-matched with 61 infants showing no signs of fetal distress or acidemia
      (controls) on the basis of gestational age and delivery method. Umbilical cord
      serum dehydroepiandrosterone sulfate and cortisol were measured, and the data
      were analyzed by two-tailed t test, Fisher's exact test, analysis of variance,
      and Tukey's multiple range test. RESULTS: Distressed infants had lower serum
      levels of dehydroepiandrosterone sulfate (3992 +/- 246 nmol/L, mean +/- SE) than
      control infants (4853 +/- 283 nmol/L); distressed infants also had higher levels
      of cortisol (412 +/- 17 nmol/L) than did control infants (299 +/- 16 nmol/L). The
      dehydroepiandrosterone sulfate/cortisol ratios in control infants (17.7 +/- 1.2)
      were almost twice those of distressed infants (10.8 +/- 0.9). These same
      relationships also were noted when the infant pairs were segregated according to
      whether delivered vaginally (21 pairs) or by cesarean section (40 pairs). The
      abnormalities in steroid levels in the distressed infants were independent of the
      presence or absence of acidemia. CONCLUSION: Intrapartum stress acutely alters
      fetal adrenal steroidogenesis, leading to increased production of cortisol and
      decreased secretion of dehydroepiandrosterone sulfate.

PMID- 8267038
TI  - Comparative trial of prednisone plus aspirin versus aspirin alone in the
      treatment of anticardiolipin antibody-positive obstetric patients.
AB  - OBJECTIVE: We compared the use of aspirin alone with combined therapy (prednisone
      plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior
      adverse pregnancy outcome. STUDY DESIGN: Thirty-nine patients meeting specific
      laboratory and clinical inclusion criteria were randomized to receive either
      combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n =
      22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and
      increased or decreased on the basis of observed changes in serial antibody
      levels. Perinatal outcomes were compared between groups. Evaluation of treatment
      related maternal complications and serial antibody titers was also accomplished.
      RESULTS: Thirty-four randomized subjects were evaluable (prednisone plus low-dose
      aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in
      the study cohort. Preterm delivery was experienced by significantly more patients
      receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22,
      respectively; p = 0.003), and prednisone exposure appeared to be an independent
      risk factor for preterm birth. CONCLUSIONS: The use of prednisone therapy in
      conjunction with low-dose aspirin does not appear to improve outcome and may
      provoke obstetric complications in antiphospholipid antibody-positive patients.

PMID- 8267039
TI  - Transfer of cocaine by the perfused human placenta: the effect of binding to
      serum proteins.
AB  - OBJECTIVES: Our purpose was to investigate the transfer of cocaine across human
      placenta and to measure the binding of cocaine to maternal and cord sera and to
      assess the effect of binding on transfer. STUDY DESIGN: Cocaine transfer by the
      in vitro perfused human placenta was studied under controlled experimental
      conditions. Protein binding of cocaine was measured by ultrafiltration in 10
      pairs of maternal and cord sera and was compared with 12 sera from nonpregnant
      females. RESULT: With perfusates of albumin (5 gm/dl) in buffer cocaine clearance
      was 1.08 +/- 0.52 ml/min, threefold greater than that of the water-soluble marker
      L-glucose. Transfer was bidirectional and nonsaturable over a concentration of
      0.02 to 4000 ng/ml. Cocaine was not detectably metabolized during perfusion.
      Replacement of albumin-buffer with human serum as maternal perfusate reduced the
      transfer rate by almost 50%, p < 0.02. Binding of cocaine was greatest by serum
      from the nonpregnant female > pregnant female (not significant) > cord serum (p <
      0.02) = albumin buffer. CONCLUSIONS: Cocaine is rapidly transferred across the
      placenta by simple diffusion without metabolic conversion. Transfer, although
      diminished, remains rapid in spite of binding to serum proteins. These several
      factors plus the poor binding by cord serum conspire to increase fetal exposure
      to the drug.

PMID- 8267040
TI  - Endotoxin, interleukin-1 beta, interleukin-6, or tumor necrosis factor-alpha do
      not acutely stimulate isolated murine myometrial contractile activity.
AB  - OBJECTIVES: Endotoxin, interleukin-1 beta, interleukin-6, and tumor necrosis
      factor-alpha have been implicated in the pathogenesis of preterm labor, but their
      acute effect on myometrial contractile activity is unknown. The objective of this
      study was to determine their effect on isolated pregnant murine myometrial
      contractile activity. STUDY DESIGN: Isometric contractions were measured in
      myometrium isolated from pregnancy day 18 Swiss-Webster mice. Frequency,
      duration, amplitude, and integrated area were compared before and after the
      addition of endotoxin (10(3) and 10(4) ng/ml) (n = 6), interleukin-1 beta (10 and
      10 ng/ml) (n = 6), interleukin-6 (1 and 10 ng/ml) (n = 6), and tumor necrosis
      factor-alpha (1 and 10 ng/ml) (n = 6). Results were analyzed with the Wilcoxon
      rank-sum test. RESULTS: The addition of endotoxin, interleukin-1 beta,
      interleukin-6, or tumor necrosis factor-alpha did not result in a change in the
      contractile activity of isolated pregnant murine myometrium compared with
      control. CONCLUSION: Endotoxin, interleukin-1 beta, interleukin-6, and tumor
      necrosis factor-alpha do not acutely increase isolated murine myometrial
      contractile activity.

PMID- 8267041
TI  - Role of extracellular calcium and calcium channels in the response of human
      placental venous smooth muscle to endothelin-1.
AB  - OBJECTIVE: Our purpose was to evaluate the role of calcium and calcium channels
      in endothelin-1-induced contraction of the smooth muscle of human placental
      veins. STUDY DESIGN: Placentas were collected after vaginal delivery at term.
      After their removal from the chorionic plate, placental veins were divided into
      rings that were suspended in organ chambers and stretched to optimal tension. In
      the first part of the study, vessels from six women were initially suspended in
      calcium-poor modified Krebs-Ringer solution. They were then treated with either
      EGTA [ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid;
      calcium chelator, 0.5 mmol/L] or calcium chloride 2.5 mmol/L (control).
      Endothelin-1 was then added cumulatively (10(-10) to 10(-7) mol/L), and the
      resulting changes in isometric tensions were recorded. In the second part of the
      study vessels from six other women were treated with either (1) normal modified
      Krebs-Ringers solution (control), (2) calcium-poor modified Krebs-Ringers
      solution, or (3) nicardipine (dihydropyridine calcium channel inhibitor, 10(-7)
      mol/L) in separate organ chambers. Endothelin-1 was then added cumulatively.
      RESULTS: Endothelin-1 produced concentration-dependent contractions in placental
      veins, with maximal tension reached at 10(-7) mol/L. Substitution of calcium-poor
      for standard Krebs-Ringers solution in the organ chamber abolished contractions
      to low endothelin-1 concentrations (< or = 10(-9) mol/L, p < 0.001) but did not
      affect the contractile response to higher concentrations. EGTA abolished
      contractions to all concentrations tested (p < 0.02). Nicardipine significantly,
      but incompletely, inhibited the contractile responses to all endothelin-1
      concentrations tested (p < 0.05). CONCLUSIONS: Endothelin-1 induces contraction
      of the smooth muscle of human placental veins, which requires the influx of
      extracellular calcium. Dihydropyridine-sensitive calcium channels represent a
      major route of entry, but other pathways participate. The fetal effects of
      nifedipine and other calcium-channel blockers deserve specific evaluation in
      intrauterine growth retardation and other pregnancies complicated by elevated
      fetal levels of endothelin-1.

PMID- 8267042
TI  - Regulation of fetal fibronectin production in human chorion cells.
AB  - OBJECTIVE: Our purpose was to evaluate the role of human chorion in production of
      fetal fibronectin and to assess the regulation of fetal fibronectin production by
      inflammatory products and cytokines. STUDY DESIGN: Human chorion cells were grown
      in culture, and at confluence cells were incubated with and without
      lipopolysaccharide, interleukin-1 beta, tumor necrosis factor-alpha, and
      acetylsalicylic acid. Fetal fibronectin production was measured in the
      supernatants by means of enzyme-linked immunosorbent assay. RESULTS: Production
      of fetal fibronectin was increased by lipopolysaccharide, interleukin-1 beta, and
      tumor necrosis factor-alpha. Acetylsalicylic acid had no effect on fetal
      fibronectin biosynthesis. CONCLUSIONS: Fetal fibronectin production by human
      chorion cells in vitro is stimulated by inflammatory products and mediators,
      which are considered to be important in the initiation of some cases of preterm
      labor.

PMID- 8267043
TI  - Fetectomy alters maternal endocrine and uterine activity rhythms in rhesus
      macaques during late gestation.
AB  - OBJECTIVE: The current study was designed to test the hypothesis that fetectomy
      will eliminate or substantially alter rhythms in maternal estradiol
      concentrations and subsequently reduce or eliminate uterine activity rhythms.
      STUDY DESIGN: Six rhesus macaques underwent surgery for catheter implantation
      between days 117 and 122 of gestation (term = 167 days). At surgery the fetuses
      were removed and the membranes and placenta remained intact. Thirteen additional
      catheterized pregnant animals served as controls. Maternal arterial blood samples
      were collected for hormone analysis at 3-hour intervals for 24 hours, starting at
      9 AM. This sampling protocol was performed four times at weekly intervals until
      151 to 157 days' gestation. RESULTS: A significant rhythm (p < 0.01) in estradiol
      was determined in the control animals with peak concentrations observed in the
      morning hours whereas the progesterone peak was observed at night. In the
      fetectomy group mean plasma estradiol concentrations decreased significantly from
      312 +/- 34 to 110 +/- 8 pg/ml throughout the study (p < 0.01). Despite a trend
      toward elevated morning levels, the estradiol rhythm was ablated. The uterine
      contractile rhythm observed in the control animals with peak activity between 10
      PM and midnight (p < 0.01) was also ablated after fetectomy. Basal concentrations
      of progesterone were significantly lower than control values. CONCLUSIONS: (1)
      Fetectomy resulted in the elimination of the maternal estradiol rhythm. (2) The
      uterine activity rhythm was lost after fetectomy. These data suggest that the
      fetus, by supplying precursors of estrogen, may play an indirect role in the
      regulation of maternal estradiol rhythms, which in turn appear to play a key role
      in regulating uterine activity rhythms.

PMID- 8267044
TI  - Actions of interleukin-4 on prostaglandin biosynthesis at the chorion-decidual
      interface.
AB  - OBJECTIVE: We determined the effects of interleukin-4 on chorion and decidual
      prostaglandin production. STUDY DESIGN: Chorion and decidual cells from term
      placentas were grown to confluence. Cells were then incubated with interleukin-4
      either alone or with other known stimulants of prostaglandin production:
      interleukin-1 beta, epidermal growth factor, ionomycin, or phorbol 12-myristate
      13-acetate. Prostaglandin E2 production was determined with a specific
      radioimmunoassay. RESULTS: Interleukin-4 alone stimulated prostaglandin E2
      production in chorion and decidual cells. Interleukin-4 significantly enhanced
      the stimulatory actions of phorbol 12-myristate 13-acetate, ionomycin, and
      epidermal growth factor but not interleukin-1 beta on prostaglandin E2
      production. CONCLUSION: Interleukin-4 stimulates prostaglandin E2 production by
      chorion and decidual cells. These data suggest that interleukin-4 production by
      immune effector cells in gestational tissues may contribute to the
      pathophysiologic features of preterm labor.

PMID- 8267045
TI  - The oxygen consumption/oxygen delivery curve in severe preeclampsia: evidence for
      a fixed oxygen extraction state.
AB  - OBJECTIVE: Increased total body oxygen consumption requirements are usually met
      by increased oxygen delivery and increased oxygen extraction. In certain
      conditions (e.g., adult respiratory distress syndrome) the ability to increase
      oxygen extraction is lost, and any increase in oxygen consumption depends on
      increased oxygen delivery. The objective of this study was to investigate the
      oxygen delivery/oxygen consumption relationship in severe preeclampsia. STUDY
      DESIGN: Thirty-two patients with severe preeclampsia (blood pressure > 160/110 mm
      Hg; 3 to 4+ proteinuria) were monitored with a pulmonary artery catheter.
      Baseline oxygen consumption and delivery in a group without volume expansion or
      pharmacologic vasodilatation were compared with those in a group who had received
      a magnesium sulfate infusion. RESULTS: Oxygen consumption, oxygen delivery,
      arterial-venous-oxygen difference, and the oxygen extraction ratio were low when
      compared to that for normal 32 to 38 week pregnancy. The oxygen extraction ratio,
      defined as the ratio of oxygen consumption to oxygen delivery, was abnormally low
      for pregnancy, especially considering the low oxygen delivery levels in these
      patients. Oxygen consumption was dependent on oxygen delivery over the entire
      range of values seen. CONCLUSIONS: Severe preeclampsia is associated with an
      abnormality of tissue oxygen extraction, as evidenced by a low and unresponsive
      oxygen extraction ratio. Oxygen consumption increases proportionately with
      increases in oxygen delivery without reaching an oxygen delivery-independent
      state. Even at high oxygen delivery levels the oxygen consumption in preeclamptic
      patients is still abnormally low for pregnancy.

PMID- 8267046
TI  - Deficient glutathione peroxidase activity in preeclampsia is associated with
      increased placental production of thromboxane and lipid peroxides.
AB  - OBJECTIVE: Thromboxane and lipid peroxide levels are abnormally increased in
      preeclamptic placentas. The cause of this increase is not known. Peroxides
      stimulate prostaglandin H2 synthase to increase thromboxane and oxygen radicals,
      which increase lipid peroxides. Glutathione peroxidase inactivates peroxides,
      thereby decreasing peroxide stimulation of prostaglandin H synthase. If
      glutathione peroxidase activity were deficient, then peroxides could increase,
      leading to increased stimulation of prostaglandin H synthase, resulting in
      increased production of thromboxane and lipid peroxides. The following study
      tested this hypothesis. STUDY DESIGN: Placental tissues from 11 normal and 11
      preeclamptic women were immediately frozen in liquid nitrogen after delivery. One
      gram of tissue from each placenta was homogenized for analysis. Placental tissues
      were also obtained from six normal pregnancies for incubation with a glutathione
      peroxidase inhibitor, N-ethylmaleimide. Samples were analyzed for glutathione
      peroxidase activity, lipid peroxides by hydrogen peroxide equivalents,
      thromboxane by thromboxane B2, and prostacyclin by 6-keto-prostaglandin F1 alpha.
      RESULTS: Glutathione peroxidase activity was significantly lower in preeclamptic
      than in normal placentas (9.41 +/- 0.05 vs 13.41 +/- 0.63 units/gm, p < 0.001,
      mean +/- SE). Lipid peroxides and thromboxane were significantly higher in
      preeclamptic than in normal placentas (hydrogen peroxide equivalents 4.23 +/-
      0.32 vs 2.84 +/- 0.27 mumol/gm, p < 0.01; thromboxane B2 215 +/- 31 vs 138 +/- 15
      ng/gm, p < 0.05), whereas prostacyclin was significantly lower (6-keto
      prostaglandin F1 alpha 23.3 +/- 2.2 vs 41.6 +/- 6.0 ng/gm, p < 0.01). Inhibition
      of glutathione peroxidase activity in normal placentas resulted in a dose
      response increase in placental production of both lipid peroxides and thromboxane
      without affecting prostacyclin, so the ratio of thromboxane to prostacyclin
      increased progressively with inhibition of glutathione peroxidase. CONCLUSIONS:
      Glutathione peroxidase activity is significantly lower, and lipid peroxides and
      thromboxane are significantly higher, in preeclamptic placentas compared with
      normal placentas. Inhibition of glutathione peroxidase activity in normal
      placentas results in significantly increased production of lipid peroxides and
      thromboxane and an increase in the thromboxane to prostacyclin ratio. We
      speculate that in normal placentas, glutathione peroxidase limits prostaglandin H
      synthase activity by reducing the amount of peroxide present, thus reducing
      peroxide stimulation of prostaglandin H synthase. In preeclampsia deficient
      glutathione peroxidase activity results in in increased peroxide levels leading
      to increased stimulation of prostaglandin H synthase, which results in increased
      production of lipid peroxides and thromboxane.

PMID- 8267047
TI  - Secretion of lipid peroxides by the human placenta.
AB  - OBJECTIVE: We attempted to determine whether the human placenta secretes lipid
      peroxides. If it does, then it could be a source of lipid peroxides in maternal
      blood. STUDY DESIGN: In study 1 isolated human placental cotyledons (n = 7) were
      perfused serially for 20-minute intervals with control Krebs-Ringer-bicarbonate
      buffer gassed with 95% oxygen and 5% carbon dioxide and Krebs-Ringer-bicarbonate
      buffer with progressively increasing concentrations of t-butyl hydroperoxide
      added (10, 25, 50, and 100 mumol/L) to stimulate endogenous lipid peroxide
      production. In study 2 placental cotyledons (n = 6) were perfused serially for 20
      minute intervals with control Krebs-Ringer-bicarbonate buffer, t-butyl
      hydroperoxide (100 mumol/L), low-dose aspirin (5 x 10(-5) mol/L), and low-dose
      aspirin plus t-butyl hydroperoxide. Maternal and fetal effluent samples were
      analyzed for lipid peroxides by hydrogen peroxide equivalents. RESULTS: In study
      1, compared with control Krebs-Ringer-bicarbonate perfusion, peroxide perfusion
      significantly increased, in a dose-response manner, placental lipid peroxide
      secretion. In study 2, aspirin completely blocked the ability of peroxide to
      increase the secretion of lipid peroxides. In both studies placental secretion of
      lipid peroxides was significantly greater toward the maternal side of the
      placenta than toward the fetal side. CONCLUSIONS: (1) The human placenta secretes
      lipid peroxides primarily into the maternal effluent. (2) Exogenous peroxide
      stimulates endogenous lipid peroxide production, which is blocked by aspirin,
      suggesting cyclooxygenase is involved in lipid peroxide production. (3) The
      placenta could be a source of circulating lipid peroxides in pregnant women.

PMID- 8267048
TI  - 5-Hydroxyeicosatetraenoic acid biosynthesis by gestational tissues: effects of
      inflammatory cytokines.
AB  - OBJECTIVE: Our purpose was to determine whether inflammatory cytokines can
      modulate the production of arachidonate lipoxygenase metabolites by gestational
      tissues. STUDY DESIGN: Primary cultures of amnion, chorion, and decidual cells
      were incubated in the presence and absence of interleukin-1 beta, tumor necrosis
      factor-alpha, and interleukin-6. Supernatants were assayed for leukotriene B4,
      leukotriene C4, 5-, 12- and 15-hydroxyeicosatetraenoic acid by means of specific
      radioimmunoassays. Cellular proteins were determined. RESULTS: 5
      Hydroxyeicosatetraenoic acid production was significantly increased by
      interleukin-1 beta and interleukin-6 treatment in amnion, chorion, and decidual
      cells. Tumor necrosis factor-alpha elicited a modest increase, which was not
      statistically significant, in mean 5-hydroxyeicosatetraenoic acid production by
      these cells. Production rates of leukotrienes B4 and C4 and 12 and 15
      hydroxyeicosatetraenoic acid were not affected by treatment with interleukin-1
      beta. CONCLUSIONS: Inflammatory cytokines generated in response to intrauterine
      infection may modulate uterine activity by stimulation of 5
      hydroxyeicosatetraenoic acid biosynthesis.

PMID- 8267049
TI  - Restoration of fetal red blood cells and plasma proteins after a moderately
      severe hemorrhage in the ovine fetus.
AB  - OBJECTIVE: We hypothesized that the fetus, in response to a moderately severe
      hemorrhage, would restore its plasma volume and red blood cells so that plasma
      volume would be returned to normal within 24 hours and red blood cell mass would
      be restored in 5 to 7 days. STUDY DESIGN: Time-dated pregnant sheep (five control
      and six hemorrhage, gestational age 124 +/- 1 [SE] days) were subjected to a 10
      day protocol. Fetal blood volume, plasma volume, red blood cell mass, and plasma
      protein mass were measured on protocol days 1, 3, 4, 6, 8, and 10. Fetal plasma
      erythropoietin and plasma iron concentrations were measured daily. On protocol
      day 3 the hemorrhage animals underwent a 120 ml fetal hemorrhage over 2 hours.
      Statistical analysis was by three-factor analysis of variance. RESULTS: Control
      animals had a progressive increase in blood volume, plasma volume, plasma protein
      mass, and red blood cell mass throughout the 10-day protocol. The 2-hour
      hemorrhage removed 39.8% +/- 1.2% of the prehemorrhage blood volume. During the 7
      day posthemorrhage recovery period fetal blood volume and red blood cell mass in
      the animals that were hemorrhaged expanded in parallel to, but remained below,
      that of the control animals. There was no difference in the expansion of fetal
      plasma volume or plasma protein mass between the two groups. After hemorrhage
      there was a nonsignificant increase in the fetal reticulocyte index in the
      animals undergoing hemorrhage. In response to the hemorrhage, erythropoietin
      levels increased and remained marginally elevated, whereas plasma iron levels
      decreased in the hemorrhaged animals relative to controls during the 7-day
      recovery period. CONCLUSIONS: The normal expansion of plasma volume and plasma
      protein mass that occurs with fetal growth was not altered by a large fetal blood
      loss. However, in spite of a transient increase in plasma erythropoietin levels
      the fetuses undergoing hemorrhage did not restore their red blood cell mass or
      blood volume. These observations suggest that the ovine fetus is able to
      withstand a significant loss of red blood cells, but fetal transfusion may be
      needed to restore fetal red blood cell mass after a moderate-to-severe fetal
      hemorrhage.

PMID- 8267050
TI  - Fetal endocrine and renal responses to in utero ventilation and umbilical cord
      occlusion.
AB  - OBJECTIVE: Fetal to neonatal transition involves a myriad of endocrine and renal
      adaptive changes triggered by multiple simultaneous stimuli. We examined the
      extent to which ventilation and umbilical cord occlusion have an impact on the
      many endocrine and renal function changes in fetal sheep at 133 +/- 1 day of
      gestation. STUDY DESIGN: Nine fetuses were chronically prepared with an
      endotracheal tube, vascular and bladder catheters, and an inflatable umbilical
      cord occluder. After a 2-hour control period fetuses were treated with
      commercially prepared surfactant and ventilated with 100% oxygen. One hour after
      the onset of stable ventilation the umbilical cord was occluded and the animals
      were monitored for 3-hours. RESULTS: In response to ventilation fetal arterial
      PO2 increased (18 +/- 1 to 86 +/- 29 mm Hg) and remained significantly above
      control values after cord occlusion. Fetal arterial pH, hematocrit, and mean
      arterial pressure and heart rate did not change during the study. Ventilation
      alone evoked significant increases in epinephrine and norepinephrine
      concentrations. Renal responses to ventilation included significant decreases in
      urine flow rate, fractional sodium excretion, and fractional water excretion.
      Neither ventilation nor cord occlusion resulted in significant changes in plasma
      concentrations of atrial natriuretic factor, arginine vasopressin, and
      angiotensin II or in glomerular filtration rate, urine osmolality, free water,
      and osmolar clearances. CONCLUSIONS: (1) Mechanical ventilation and oxygenation
      alone increase circulating fetal catecholamine levels. (2) The addition of
      umbilical cord ligation has minimal impact on fetal endocrine and renal adaptive
      responses.

PMID- 8267051
TI  - Maximal lymph flow in the ovine fetus.
AB  - OBJECTIVE: This study was designed to determine the maximal left thoracic duct
      lymph flow rate in late-gestation ovine fetuses. STUDY DESIGN: Chronically
      catheterized sheep fetuses (n = 8) with indwelling left thoracic lymph duct and
      vascular catheters were studied > or = 5 days after surgery at 136 +/- 1 (SE)
      days' gestation. To increase lymph flow rate, 4 L of warm lactated Ringer's
      solution were infused intravenously into the fetus over 4 hours, because this
      causes mild edema as determined ultrasonographically. RESULTS: During a 1-hour
      preinfusion period lymph flow rate was 0.53 +/- 0.06 ml/min. During the infusion
      increases occurred in fetal arterial (7.6 +/- 1.0 mm Hg) and venous (2.4 +/- 0.3
      mm Hg) pressures (p < 0.001). Lymph flow rate increased and reached a plateau
      after 1 hour at 339% +/- 30% of preinfusion values (p < 0.001). When the infusion
      was terminated, fetal arterial and venous pressures rapidly returned to
      preinfusion levels. Lymph flow rate gradually decreased during the first 30
      minutes and stabilized at 97% +/- 17% above control during the subsequent 30
      minutes. Analysis of lymph flow rate as a function of outflow pressure revealed
      that the increases in flow occurred because of an upward shift in the plateau
      flow rate with no change in the stop-flow pressure. CONCLUSIONS: (1) Fetal left
      thoracic duct lymph flow rate can increase significantly above basal values and
      therefore is an important safety factor against fetal edema formation. (2) The
      maximal lymph flow rate appears to be 3.4 times normal when venous pressure is
      elevated and two times normal when venous pressure is normal.

PMID- 8267052
TI  - Effects of asphyxia on the fetal lamb brain.
AB  - OBJECTIVE: Our purpose was to study the effect of fetal asphyxia on the release
      of hypoxanthine and xanthine in cerebrospinal fluid and on brain histologic
      characteristics. STUDY DESIGN: In seven fetal lambs (3 to 5 days after surgery,
      gestational age 124.3 +/- 2.6 days) asphyxia was induced by restriction of
      uterine blood flow. RESULTS: Fetal pH and base excess were reduced to 6.99 +/-
      0.02 and -17.6 +/- 0.9 mmol/L, respectively. Cerebral blood flow increased during
      asphyxia and returned to normal in the recovery phase. Maximum concentrations of
      cerebrospinal fluid hypoxanthine and xanthine were reached in the normoxemic
      recovery phase. This high level of substrates during normoxemia facilitates
      oxygen free radical formation and may thus aggravate postasphyctic brain damage.
      Histologic evaluation of the brain 3 days after the insult showed a variable
      degree of edema. Coagulative neuronal changes, characteristic of irreversible
      cell death, were only occasionally detected. These changes were most obvious in
      the Purkinje cells of the cerebellum. CONCLUSIONS: Fetal asphyxia induced by
      uterine blood flow restriction is associated with high levels of cerebrospinal
      fluid hypoxanthine and xanthine in the recovery phase. Microscopically detectable
      brain damage, although not extensive, is mainly located in the cerebellum.

PMID- 8267053
TI  - Cocaine acutely increases rat myometrial contractile activity by mechanisms other
      than potentiation of adrenergic pathways.
AB  - OBJECTIVE: We hypothesized that cocaine acutely increases contractile activity in
      isolated rat myometrium and that this effect is solely caused by potentiation of
      adrenergic pathways. STUDY DESIGN: Isometric contractions were measured in
      myometrium isolated from virgin and day-18 pregnant Sprague-Dawley rats.
      Frequency, duration, amplitude, and integrated area were compared before and
      after the addition of cocaine (10(-6) to 10(-4) mol/L) by means of analysis of
      variance and Duncan's multiple-range test. The effects of alpha-adrenergic
      receptor antagonists (prazosin 10(-6) mol/L and yohimbine 10(-6) mol/L) and beta
      adrenergic receptor antagonist (DL-propranolol 2 x 10(-6) mol/L) were assessed.
      RESULTS: Contraction duration, expressed relative to control, increased acutely
      after cocaine (10(-5) mol/L) administration in pregnant (1.70 +/- 0.20) and
      nonpregnant (1.36 +/- 0.24) myometrium (mean +/- SE, p < 0.05), as did integrated
      area (pregnant 3.47 +/- 0.97, nonpregnant 2.48 +/- 0.66) (mean +/- SE, p < 0.05).
      These effects were not completely inhibited by adrenergic blockade. CONCLUSION:
      Cocaine acutely increases the duration and integrated area of spontaneous
      contractions in isolated rat myometrium by mechanisms not completely explained by
      inhibition of catecholamine reuptake and potentiation of adrenergic pathways.

PMID- 8267054
TI  - Is uterine blood flow controlled locally or systemically in the pregnant rabbit?
AB  - OBJECTIVE: We tested the hypothesis that uterine blood flow is regulated by
      systemic circulating factors. The alternative hypothesis is that uterine blood
      flow is regulated by local factors. STUDY DESIGN: Adult female New Zealand White
      rabbits were subjected to a unilateral tubal ligation and thereafter allowed to
      become pregnant (n = 9). A group of nonpregnant one-tube-ligated animals served
      as controls (n = 8). On day 21 of gestation uterine blood flow in the pregnant
      and nonpregnant uterine horns were measured with 15 microns microspheres. The
      concentration of prostaglandin E2 metabolites were measured in blood from the
      uterine veins and from the arterial circulation. RESULTS: Absolute uterine blood
      flow in the pregnant uterine horn was 12.9 +/- 4.7 versus 5.2 +/- 1.4 ml in the
      nonpregnant horn (p < 0.05). However, when expressed by blood flow per gram of
      tissue they were not different (p > 0.1). The uterine blood flow for the
      nonpregnant uterine horn in the pregnant animals was the same as that of the
      horns from nonpregnant animals. The level of prostaglandin E metabolites was
      greater in the uterine vein draining the pregnant horn compared to the
      nonpregnant horn (p < 0.05). CONCLUSION: These data support the conclusion that
      the increase in uterine blood flow observed during pregnancy is controlled
      largely by local factors induced by pregnancy.

PMID- 8267055
TI  - Characteristics of vascular smooth muscle in the maternal resistance circulation
      during pregnancy in the rat.
AB  - OBJECTIVE: Our purpose was to determine if pregnancy results in a decrease in
      arterial sensitivity to receptor-independent stimuli and a change in vascular
      smooth muscle membrane potential. STUDY DESIGN: Mesenteric resistance arteries
      from late pregnant (n = 19) and age-matched virgin control (n = 20) Sprague
      Dawley rats were studied in a pressurized arteriograph system or isometric
      myograph. RESULTS: Arteries from pregnant rats were less sensitive to membrane
      depolarization by K+ than were those from nonpregnant rats (mean effective
      concentration that produced a 50% response 49 vs 39 mmol/L, pregnant vs
      nonpregnant, p < 0.05). Arterial basal tone and the myogenic response to
      increasing pressure steps were also reduced in arteries from pregnant rats
      compared with nonpregnant controls. The vascular smooth muscle membrane of the
      arteries from the pregnant rats was hyperpolarized compared with that from the
      control rats (-64 mV from pregnant rats vs -57 mV from nonpregnant rats, p <
      0.01). This was associated with a reduction in vasomotion in the arteries from
      the pregnant rats (10% for pregnant rats vs 45% from nonpregnant rats, p < 0.01).
      CONCLUSION: Pregnancy results in alterations of the vascular smooth muscle,
      including changes in the regulation of membrane potential and a reduced
      sensitivity to receptor-independent stimuli.

PMID- 8267056
TI  - Basic fibroblast growth factor and its receptor messenger ribonucleic acids are
      expressed in human ovarian epithelial neoplasms.
AB  - OBJECTIVE: Our purpose was to determine whether basic fibroblast growth factor is
      present in, and synthesized by, human ovarian epithelial neoplasms and to
      evaluate the expression of gene for the basic fibroblast growth factor receptor.
      STUDY DESIGN: The synthesis of basic fibroblast growth factor and its receptor
      was investigated in seven primary human ovarian epithelial neoplasms. Neoplastic
      tissues were homogenized and the cytoplasmic extracts purified by heparin
      sepharose chromatography with a linear salt gradient of 0.6 to 3 mol/L sodium
      chloride in Tris-hydrochloric acid. The in situ synthesis of basic fibroblast
      growth factor and its receptor was demonstrated by polymerase chain reaction.
      Total ribonucleic acid was reverse transcribed and then amplified with two
      oligonucleotide primers specific for the bovine and human basic fibroblast growth
      factor gene and its human receptor gene. RESULTS: As assessed by both bioassay
      and radioimmunoassay a peak of basic fibroblast growth factor-like activity was
      present in all tumors in the chromatographic fractions eluted with 3 mol/L sodium
      chloride. The mitogenic effect on bovine adrenocortical endothelial cell
      proliferation varied from 35% to 153% above control cultures. Levels of basic
      fibroblast growth factor-like immunoreactivity were between 4 and 33 ng/ml.
      Qualitatively similar results were obtained after purifying the cytoplasmic
      extract of dispersed human ovarian tumor cells. The mitogenic effect was
      completely abolished by a specific neutralizing anti-basic fibroblast growth
      factor antibody. Single major deoxyribonucleic acid bands of the expected size
      (354 and 661 bp) were detected in all tumors studied. The identify of this
      material with the human basic fibroblast growth factor sequence was confirmed by
      restriction enzyme analysis. CONCLUSION: These data demonstrate that both basic
      fibroblast growth factor and its receptor are present in and synthesized by human
      ovarian tumor cells. Thus basic fibroblast growth factor might stimulate their
      abnormal proliferation through an autocrine mechanism.

PMID- 8267057
TI  - Proliferative index of human luteinized granulosa cells varies as a function of
      ovarian reserve.
AB  - OBJECTIVE: We examined whether the proliferative index of luteinized granulosa
      cells, as determined by flow cytometry, varied as a function of a woman's ovarian
      reserve, as reserve, as reflected by follicular-phase day 3 serum follicle
      stimulating hormone. STUDY DESIGN: This prospective cohort study consisted of 19
      women of similar chronologic age preparing for in vitro fertilization-embryo who
      met specific day 3 serum follicle-stimulating hormone criteria. The "low follicle
      stimulating hormone" group consisted of 11 women with day 3 serum follicle
      stimulating hormone levels < or = 6 IU/L. The "high follicle-stimulating hormone"
      group consisted of eight women with day 3 serum follicle-stimulating hormone
      levels > or = 18 IU/L. A total of 56 preovulatory follicles containing > or =
      10(4) luteinized granulosa cells were examined by flow cytometry. The low
      follicle-stimulating hormone group was compared with the high follicle
      stimulating hormone group to examine proliferative index as a function of serum
      day 3 follicle-stimulating hormone levels. RESULTS: The low follicle-stimulating
      hormone group had a greater proliferative index (11.1% +/- 0.4%) than did the
      high follicle-stimulating hormone group (8.3% +/- 0.6%), p < 0.001). This study
      demonstrates that in spite of the same chronologic age, luteinized granulosa
      cells from preovulatory follicles of women with day 3 serum follicle-stimulating
      hormone levels > or = 18 IU/L have a 25% decreased proliferative index compared
      with luteinized granulosa cells from women with day 3 serum follicle-stimulating
      hormone levels < or = 6. CONCLUSIONS: This suggests that granulosa cell
      proliferation is influenced by ovarian reserve and may explain in part the more
      favorable response to ovulation induction protocols that younger women
      demonstrate compared with women of more advanced reproductive age.

PMID- 8267058
TI  - Oral dehydroepiandrosterone in physiologic doses modulates immune function in
      postmenopausal women.
AB  - OBJECTIVE: This study tests the hypothesis that dehydroepiandrosterone or its
      metabolic products are immunomodulatory in postmenopausal women with relative
      adrenal androgen deficiency. STUDY DESIGN: A prospective, randomized, double
      blind, crossover study of 11 subjects with 3-week treatment arms separated by a 2
      week washout period was performed. Immunologic evaluation at the beginning and
      end of the treatment arms consisted of flow cytometry to delineate T-cell
      populations, in vitro T-cell mitogenic response and cytokine production, and
      natural killer cell cytotoxicity. Statistical analysis was based on a split-plot
      design with analysis of variance with repeated measures. RESULTS:
      Dehydroepiandrosterone supplementation decreased CD4+ (helper) T cells and
      increased CD8+/CD56+ (natural killer) cells. Although T-cell mitogenic and
      interleukin-6 responses were inhibited, natural killer cell cytotoxicity
      increased dramatically. CONCLUSIONS: These data provide the first in vivo
      evidence in human for an immunomodulatory effect of dehydroepiandrosterone. The
      salutary immune changes could account for clinical and experimental evidence of
      antioncogenic effects of this steroid. This study provides a strong rationale for
      further clinical studies on dehydroepiandrosterone supplementation in adrenal
      androgen-deficient states.

PMID- 8267060
TI  - Fibrinolytic parameters in women undergoing ovulation induction.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of elevated
      levels of circulating estradiol on the clotting and fibrinolytic system in
      patients undergoing controlled ovarian hyperstimulation. STUDY DESIGN: Fifty-two
      patients undergoing controlled ovarian hyperstimulation with human menopausal
      gonadotropins or urofollotropin were asked to participate. Blood for hemostasis
      parameters was obtained on the days that patients returned for estradiol
      sampling. Sample days were identified as cycle days 1 to 5 (baseline), 6 to 9,
      and 10 to 14. Each factor was analyzed by repeated-measures analysis of variance
      and correlation analysis. RESULTS: A significant decline was observed for tissue
      plasminogen activator antigen and plasminogen activator inhibitor type 1 activity
      from baseline to cycle days 10 to 14. As serum estradiol levels increased
      throughout each phase (maximum mean estradiol 739.8 pg/ml), a significant linear
      decrease was observed for both tissue plasminogen activator antigen and
      plasminogen activator inhibitor type 1 activity, whereas thrombin-antithrombin
      III complexes did not change significantly. A significant positive correlation
      was also observed for plasminogen activator inhibitor activity and tissue
      plasminogen activator antigen level over all cycle days examined. CONCLUSION:
      Down-regulation of the fibrinolytic system was observed as estradiol levels
      increased. However, thrombin formation did not change, thus suggesting that
      elevated circulating estradiol alone does not predispose to a thromboembolic
      event.

PMID- 8267059
TI  - Insulin sensitivity is decreased in normal women by doses of ethinyl estradiol
      used in oral contraceptives.
AB  - OBJECTIVE: We determined the independent effects of various doses of ethinyl
      estradiol used in oral contraceptives or norethindrone acetate, as well as their
      combination, on insulin sensitivity in normal women. STUDY DESIGN: Thirty-three
      normal ovulatory female volunteers were recruited for this study. Insulin
      tolerance tests were performed after carbohydrate loading to determine the
      kinetic disappearance of glucose and insulin. After initial testing the women
      were randomized into four groups: ethinyl estradiol 20 micrograms, 35 micrograms,
      and 50 micrograms and norethindrone 1 mg. Insulin tolerance tests were repeated
      after 1 month of treatment and again after a second month, when all ethinyl
      estradiol groups received the addition of norethindrone 1 mg to their doses of
      ethinyl estradiol. Plasma glucose and insulin were measured, and insulin
      sensitivity (K(itt) glucose) and the disappearance of insulin (K(itt) insulin)
      were calculated. RESULTS: All groups were comparable at baseline, and no
      significant changes in fasting glucose and insulin were evident with treatment.
      After ingestion of 50 micrograms ethinyl estradiol the K(itt) glucose value
      decreased significantly (p < 0.03) and ingestion of 20 micrograms and 35
      micrograms showed individual changes, but as groups the changes were not
      statistically significant. All ethinyl estradiol groups combined had a
      significant decrease in K(itt) glucose (p < 0.01). Norethindrone 1 mg alone did
      not change K(itt) glucose values, and after the addition of norethindrone to
      ethinyl estradiol, K(itt) glucose values normalized. K(itt) insulin values were
      also lower with treatment but were lower with ethinyl estradiol plus
      norethindrone compared with ethinyl estradiol alone (p < 0.04), suggesting an
      attenuation of insulin clearance with the progestin. CONCLUSION: Ethinyl
      estradiol alone decreases insulin sensitivity, and this may occur at lower doses,
      but norethindrone 1 mg does not appear to do so. However, progestins may alter
      insulin clearance.

PMID- 8267061
TI  - Thrombosis and hormone replacement therapy in postmenopausal women.
AB  - OBJECTIVE: The effects of postmenopausal hormone replacement therapy on
      thrombosis remain controversial. We tested the hypothesis that estrogen or
      progesterone has no significant effect on thrombosis by means of newly developed
      markers of blood clotting, specifically prothrombin fragment 1 + 2, a marker of
      factor Xa generation, and thrombin-antithrombin III complex, a marker of thrombin
      generation. STUDY DESIGN: A prospective study that included 106 women, 68
      postmenopausal women on hormone replacement therapy and 38 postmenopausal
      controls, was performed. Plasma levels of prothrombin fragment 1 + 2 and thrombin
      antithrombin III complex were measured by enzyme-linked immunosorbent assay.
      Multivariate analysis of the covariance was used for statistical analysis,
      controlling for patient's age because the hormone replacement therapy group was
      older. RESULTS: There were no statistically significant differences between the
      hormone replacement therapy and control groups in either of the clotting
      parameters measured. A comparison of the levels of prothrombin fragment 1 + 2 and
      thrombin-antithrombin III complex in patients receiving estrogen alone or
      estrogen plus progestin also revealed no differences. CONCLUSIONS: Current doses
      of postmenopausal hormone replacement therapy do not appear to enhance in vivo
      clotting. Thromboembolic complications among postmenopausal women receiving
      hormone replacement therapy may therefore be secondary to congenital or other
      acquired coagulation defects.

PMID- 8267062
TI  - Hysteroscopic findings in patients with a cervical polyp.
AB  - OBJECTIVE: Our objective was to determine the presence of intrauterine lesions in
      patients with a cervical polyp. STUDY DESIGN: We performed a retrospective
      analysis to determine the influence of hormonal treatment and age on 165 patients
      with a cervical polyp and bleeding on admission. All 165 patients underwent a
      diagnostic hysteroscopy to rule out intrauterine lesions, including polyps,
      fibroids, hyperplasia, and adenocarcinoma. RESULTS: Endometrial polyps were found
      in up to 26.7% of patients who had a cervical polyp. In patients undergoing a
      combined pill treatment this incidence was much lower (8.3%). Menopausal patients
      had a 56.8% incidence of cervix-related endometrial polyps, and hormone
      replacement therapy did not significantly increase (45.7% vs 28.6%) the incidence
      of coexisting polyps. All cervical polyps present during tamoxifen treatment were
      associated with endometrial polyps. Abnormal vaginal bleeding was of no clinical
      significance in excluding concomitant endometrial polyps. CONCLUSIONS: All
      menopausal patients with a cervical polyp could benefit from a diagnostic
      hysteroscopy. Premenopausal patients receiving a combined pill treatment are the
      least likely to have coexistent endometrial polyps.

PMID- 8267063
TI  - The risk of pulmonary edema and colloid osmotic pressure changes during magnesium
      sulfate infusion.
AB  - OBJECTIVES: The purposes of this study were to evaluate the effect of magnesium
      sulfate therapy on colloid osmotic pressure and to determine whether changes in
      colloid osmotic pressure increased the risk of pulmonary edema. STUDY DESIGN:
      During a 1-year time period 294 patients received parenteral magnesium sulfate
      for the treatment of preterm labor or preeclampsia. Both changes in colloid
      osmotic pressure and magnesium sulfate values and their relationship to clinical
      outcome parameters were analyzed. RESULTS: Serum magnesium levels were similar
      for both patients with preeclampsia and patients with preterm labor. Pulmonary
      edema developed in only four patients, all of whom had preeclampsia and low
      colloid osmotic pressure values. CONCLUSIONS: This study demonstrated that
      parenteral magnesium sulfate therapy does not cause significant changes in
      colloid osmotic pressure values until nearly 48 hours of continuous therapy.

PMID- 8267064
TI  - Fetal catecholamine responses to vibroacoustic stimulation.
AB  - OBJECTIVE: The aim of this study was to determine whether fetal vibroacoustic
      stimulation caused a surge of catecholamines from the fetal sympathoadrenal
      system. STUDY DESIGN: A randomized, prospective, controlled trial was performed
      at The Queen Mother's Hospital, Glasgow. Circulating catecholamine levels in cord
      blood from a group of fetuses who received vibroacoustic stimulation 1 to 2
      minutes before delivery by elective cesarean section (n = 25) were compared with
      those from a group of controls (n = 23) (Mann-Whitney U test). Fetal heart rate
      response to vibroacoustic stimulation was recorded in 10 additional pregnancies
      under identical experimental conditions. RESULTS: No differences were found in
      norepinephrine or epinephrine levels between the vibroacoustic stimulation group
      and the control group. A positive fetal heart rate response was observed in seven
      of 10 fetuses tested. Fetal norepinephrine levels were also found to be
      influenced by maternal blood pressure and administration of ephedrine.
      CONCLUSIONS: Under these conditions vibroacoustic stimulation does evoke the
      characteristic fetal heart rate response, but it does not induce a surge of
      catecholamines from the fetal sympathoadrenal system. Therefore it is unlikely
      that the immediate fetal heart rate response to vibroacoustic stimulation is
      induced by a surge in systemic catecholamines.

PMID- 8267065
TI  - Hormone production by the postmenopausal ovary in cases of benign ovarian
      neoplasia.
AB  - OBJECTIVE: The objective of this study was to determine whether hormone
      production by postmenopausal ovaries containing benign ovarian tumors differed
      from that of normal postmenopausal ovaries. STUDY DESIGN: The sera of 32
      postmenopausal patients were assayed before and after bilateral oophorectomy for
      estrone, 17 beta-estradiol, androstenedione, testosterone, and
      dehydroepiandrosterone sulfate. The data from all patients as a group were
      analyzed, followed by analysis of the data from 15 patients with normal ovaries
      separately from the remaining 17 patients who had nonfunctioning, benign ovarian
      tumors. RESULTS: For patients with benign ovarian tumors there was a
      statistically significant drop in estrone (from a presurgical level of 55.8 +/-
      46.3 pg/ml to a postoperative level of 29.9 +/- 10.2 pg/ml, p < 0.03) and 17 beta
      estradiol (from 18.6 +/- 14.1 pg/ml preoperatively to 9.8 +/- 3.8 pg/ml
      postoperatively, p < 0.02). For postmenopausal woman with normal ovaries there
      was no significant drop in estrone or 17 beta-estradiol after bilateral
      oophorectomy. There was a statistically significant drop in testosterone and
      androstenedione after bilateral oophorectomy both for women with normal ovaries
      and for those with benign tumors. No significant differences in
      dehydroepiandrosterone sulfate were noted in either group. CONCLUSIONS: These
      data suggest that, although normal postmenopausal ovaries have not been
      demonstrated to secrete clinically significant amounts of estrogen, those that
      contain benign ovarian tumors do secrete small but significant amounts of estrone
      and 17 beta-estradiol. Both tumor-containing and normal ovaries secrete the
      androgens androstenedione and testosterone, this secretion not being
      significantly influenced by the presence of a tumor.

PMID- 8267066
TI  - Effect of methyldopa and isradipine on fetal heart rate pattern assessed by
      computerized cardiotocography in human pregnancy.
AB  - OBJECTIVE: The effects of two antihypertensive drugs, methyldopa and isradipine,
      on fetal heart rate pattern were analyzed by computerized cardiotocography. STUDY
      DESIGN: The first part of the study was a prospective, randomized, controlled
      trial of 19 women with preeclampsia in the third trimester given 2.5 mg of oral
      slow-release isradipine twice a day or 250 mg of methyldopa three times a day. In
      a second part of the study 23 women with preeclampsia in the third trimester
      given 5 mg of oral slow-release isradipine twice a day were compared with 23
      matched controls without medication. Main outcome measures were maternal blood
      pressure and mean baseline fetal heart rate, fetal movements, number of
      accelerations, periods of high and low baseline variability, and mean baseline
      heart rate variability. RESULTS: Compared with the pretreatment value, the mean
      arterial blood pressure decreased significantly in all drug treatment groups.
      Fetal heart rate characteristics were not significantly changed during drug
      treatment or bed rest. CONCLUSION: The various features of the fetal heart rate
      pattern evaluated by computerized methods were not influenced by treatment with
      methyldopa or isradipine.

PMID- 8267067
TI  - Relationship between the fetal biophysical profile score, umbilical artery
      Doppler velocimetry, and fetal blood acid-base status determined by
      cordocentesis.
AB  - OBJECTIVE: Fetal hypoxia-acidosis is part of the terminal pathway leading to
      intrauterine fetal death. A central premise of antepartum surveillance is that
      identification and timely delivery of the hypoxic or acidotic fetus will prevent
      intrauterine death and decrease long-term neurologic damage. The optimal method
      to identify fetal hypoxia-acidosis has not been determined. We attempted to
      compare the performance of the biophysical profile score and umbilical artery
      Doppler velocimetry in the identification of fetal acidemia, hypoxemia, and
      hypercarbia as determined by pH and gas analysis of fetal blood obtained by
      cordocentesis. STUDY DESIGN: Fetal biophysical profile and umbilical artery
      Doppler velocimetry studies were performed before cordocentesis in 24 patients
      (26 to 40 weeks). Umbilical vein pH and blood gas values were determined in all
      cases. The pulsatility index of the umbilical artery was obtained with pulsed
      Doppler equipment. Receiver-operator characteristic curve analysis and stepwise
      multiple logistic regression were performed to examine the relationship between
      biophysical profile score, umbilical artery Doppler velocimetry, and acid-base
      status. RESULTS: The prevalence of fetal acidemia (pH 2 SD below the mean for
      gestational age) was 41.7% (10/24). There was a significant relationship between
      the change in umbilical artery pulsatility index and fetal acidemia (chi 2 =
      26.6, p < 0.001) and hypercarbia (chi 2 = 22.9, p < 0.001), but not hypoxemia
      (chi 2 = 1.0, p > 0.1), and between the biophysical profile score and fetal
      acidemia (chi 2 = 11.1, p < 0.001) and hypercarbia (chi 2 = 9.0, p < 0.005), but
      not hypoxemia (chi 2 = 2.3, p > 0.1). Stepwise multiple logistic regression
      demonstrated that umbilical artery Doppler velocimetry was a better explanatory
      variable for acidemia and hypercarbia than the biophysical profile score.
      CONCLUSION: A strong relationship between the degree of fetal acidemia and
      hypercarbia and the results of umbilical artery Doppler velocimetry and
      biophysical profile was found. However, umbilical artery Doppler velocimetry was
      a better explanatory variable for these outcome than the biophysical profile
      score.

PMID- 8267068
TI  - Reversal of oligohydramnios with subtotal immersion: a report of five cases.
AB  - OBJECTIVE: The purpose was to summarize five cases where subtotal immersion was
      associated with an increase in the amniotic fluid index. STUDY DESIGN: Five women
      with oligohydramnios, as defined by an amniotic fluid index < 8 cm, who underwent
      subtotal (shoulder-deep) immersion therapy are described. RESULTS: The mean
      pretreatment amniotic fluid index was 4.9 +/- 3 cm. After immersion therapy was
      instituted, the amniotic fluid index increased an average of 6 +/- 2.2 cm. In
      three subjects whose immersion therapy was discontinued, the amniotic fluid index
      fell an average of 4.7 cm. CONCLUSION: Subtotal immersion may help reverse
      oligohydramnios stemming from uteroplacental insufficiency.

PMID- 8267069
TI  - Endometrial carcinoma in postmenopausal women: evaluation by transvaginal color
      Doppler ultrasonography.
AB  - OBJECTIVE: This study was conducted to evaluate the role of transvaginal color
      Doppler ultrasonography in detecting endometrial carcinoma in postmenopausal
      women and in evaluating the depth of myometrial invasion and tumor staging. STUDY
      DESIGN: A group of 750 postmenopausal women were examined by transvaginal color
      Doppler ultrasonography 1 day before the planned hysterectomy. Histopathologic
      and blood flow characteristics were evaluated. Analysis of variance was used to
      test the significance among the subgroups. RESULTS: Thirty-five women had
      endometrial carcinoma; 32 (91.4%) cases were detected by transvaginal color
      Doppler ultrasonography. Visualization of abnormal blood flow within the
      endometrium was 100% in the diagnosed cases with resistance index near or < 0.40,
      which constituted a statistically significant difference compared with that of
      endometrial hyperplasia. No flow was detected in normal, atrophic, and in 92% of
      cases with hyperplastic endometria. The color Doppler ultrasonography depicted 18
      of 19 histologically proved cases of myometrial invasion. Three asymptomatic
      cases were discovered on the basis of morphologic and blood flow patterns.
      CONCLUSION: Transvaginal color Doppler ultrasonography can depict endometrial
      carcinoma, even in asymptomatic women, determine the depth of myometrial
      invasion, and help in tumor staging.

PMID- 8267070
TI  - Ultrasonographic identification of an ectopic intrauterine contraceptive device
      within the bladder: a case report.

PMID- 8267071
TI  - Intrapartum fetal pulse oximetry in the presence of fetal cardiac arrhythmia.
AB  - We report our experience with a reflectance pulse oximeter in intrapartum
      monitoring of a fetus with atrial flutter and heart block. During labor fetal
      arterial oxygen saturation ranged between 50% and 85%. Spontaneous vaginal
      delivery occurred with good maternal and neonatal outcome.

PMID- 8267072
TI  - Fatal superior sagittal sinus thrombosis associated with internal jugular vein
      catheterization.

PMID- 8267073
TI  - Fetal choroid plexus cysts in association with cri du chat (5p-) syndrome.
AB  - The significance of fetal choroid plexus cysts is controversial. We report a case
      of antenatally detected cri du chat syndrome (5p-) in one fetus of a twin
      pregnancy in association with bilateral fetal choroid plexus cysts and
      unassociated with other structural malformations. Choroid plexus cysts may be
      nonspecific markers for chromosomal anomalies.

PMID- 8267074
TI  - Female circumcision: obstetric issues.
AB  - Female circumcision is a problem unfamiliar to most Western obstetrician
      gynecologists. We present a case illustrative of the unique management problems
      posed by these patients during labor. A method of releasing the anterior vulvar
      scar tissue to allow vaginal delivery is described. Sensitivity and a
      nonjudgmental approach as to what is culturally appropriate care for these women
      are of paramount importance.

PMID- 8267075
TI  - Breast infiltration by acute lymphoblastic leukemia during pregnancy.
AB  - A case of bilateral breast infiltration as the initial manifestation of FAB-L3
      leukemia during pregnancy is reported. This rare presentation is usually
      associated with Burkitt's lymphoma or FAB-L3 leukemia. A high suspicion of the
      presence of hematologic malignancy and appropriate evaluation are indicated in
      the presence of this clinical manifestation.

PMID- 8267076
TI  - Reverse end-diastolic umbilical artery velocity in a case of intrauterine fetal
      death at 14 weeks' gestation.
AB  - A case of intrauterine fetal death at 14 week's gestation in a mother with
      systemic lupus erythematosus is described. Doppler ultrasonography performed
      within 24 hours before fetal death showed reverse end-diastolic flow velocities
      on umbilical artery velocity waveforms. The placental alteration causing this
      early gestation is discussed.

PMID- 8267077
TI  - Fetal pulmonary cyst treated by repeated thoracocentesis.
AB  - This is a report of prenatal diagnosis and successful therapy of a septated fetal
      pulmonary cyst by repeated puncturing. This treatment was performed under
      ultrasonographic guidance for signs of fetal cardiac decompensation. This made
      normal development of the lungs possible.

PMID- 8267078
TI  - Eclampsia in association with partial molar pregnancy and congenital
      abnormalities.
AB  - A case of eclampsia in association with partial molar pregnancy is described.
      Cytogenetic analysis confirmed a 69,XXX karyotype, and pathologic examination of
      the fetus showed a meningomyelocele, exomphalos, incomplete intestinal rotation,
      and cerebral ventricular dilatation.

PMID- 8267079
TI  - Vasa previa: prenatal diagnosis with transvaginal color Doppler flow imaging.
AB  - Vasa previa carries a significant risk for fetal exsanguination and death at the
      time of membrane rupture. The diagnosis is rarely made before the onset of
      vaginal bleeding. We report the prenatal diagnosis of vasa previa with
      transvaginal color Doppler flow imaging in an asymptomatic patient with a
      succenturiate placenta.

PMID- 8267080
TI  - Prenatal diagnosis of spontaneous rupture of the fetal bladder with color Doppler
      ultrasonography.
AB  - Rupture of the fetal-neonatal bladder that results in urinary ascites has rarely
      been reported in the literature. In this report we present the first case of
      spontaneous rupture of the fetal bladder in which the diagnosis was made
      prenatally by means of color Doppler ultrasonography.

PMID- 8267081
TI  - Laparoscopic capacitance: a mystery measured. Experiments in pigs with
      confirmation in the engineering laboratory.
AB  - OBJECTIVES: Our purpose was to determine whether capacitive currents induced in
      operative laparoscopes during endoscopic electrosurgery can cause unintentional
      injury and to measure these currents in the laboratory. STUDY DESIGN: In five
      anesthetized live pigs we tested whether capacitive currents generated in
      operative laparoscopes by unipolar instruments cause serosal injury. These
      currents were then measured in the clinical engineering laboratory. RESULTS: In
      the setting examined by us serosal injury by capacitive currents occurred only
      with high generator output power. In the laboratory the maximum power of these
      capacitive currents measured 2.5 W. CONCLUSIONS: Capacitive coupling between
      unipolar instruments and 10 mm operating laparoscopes requires relatively high
      generator output to cause serosal injury. Lower generator output settings may
      cause injury with electrosurgical generators capable of higher voltages than the
      units used in this study (Valleylab SSE2L and Force 2).

PMID- 8267082
TI  - Uterine electromyography: a critical review.
AB  - On the basis of a literature review, this work summarizes uterine animal and
      human electromyographic information obtained at cellular, myometrial, and
      abdominal levels during gestation and parturition. We show that both internal and
      external electromyograms occur in phase with intrauterine pressure increase and
      exhibit similar spectra, including a slow wave (0.01 < frequency < 0.03 Hz)
      probably because of mechanical artifacts and a fast wave whose frequency content
      can be subdivided into a low-frequency band always present in every contraction
      and a high-frequency band related to efficient parturition contractions.
      Application of classic spectral techniques to electromyogram envelopes has
      identified group propagation but not pacemaker areas. However, no time delay or
      classic propagation has been demonstrated by applying the same spectral
      techniques to the electromyogram itself, probably because of the nonlinearity and
      three-dimensional nature of the propagating process.

PMID- 8267083
TI  - Validity of dipstick analysis as a method of screening for proteinuria in
      pregnancy.

PMID- 8267084
TI  - A caveat for authors who quote statistics and for referees who accept them.

PMID- 8267085
TI  - Interval to treatment in endometrial cancer.

PMID- 8267086
TI  - Detection of an atypical invasive mole in an ectopic pregnancy by transvaginal
      color-flow Doppler.

PMID- 8267087
TI  - Does maternal hyperoxygenation result in fetal oxygenation?

PMID- 8267088
TI  - On the cause of preterm labor and birth.

PMID- 8267089
TI  - Benefit-cost analysis of preschool education: findings from a 25-year follow-up.
AB  - A 25-year study of the Perry Preschool program provides the basis for a
      comprehensive benefit-cost analysis of the long-term effects of a preschool
      education program on children growing up in poverty. Findings indicate that the
      preschool education program produced economic benefits to participants and to the
      general public that greatly exceeded the costs of the program.

PMID- 8267090
TI  - Protecting severely abused children: clarifying the roles of criminal justice and
      child welfare.
AB  - Child abuse legislation and increased public scrutiny have made child abuse the
      main focus of child welfare agencies. As a criminal act, severe child abuse
      should be dealt with by the criminal justice system to protect both endangered
      children and the rights of accused parents. Thus relieved of excessive demands,
      child welfare agencies could refocus on treatment and services to economically
      disadvantaged clients. A framework for intervention in allegations of child abuse
      is proposed.

PMID- 8267091
TI  - Federal legislation for rights of persons with mental illness: obstacles to
      implementation.

PMID- 8267092
TI  - An ecological, interpersonal skills approach to drop-out prevention.
AB  - Interventions to keep students in school have tended to be deficit-oriented and
      have met with little success. Attention to the school ecology and its ability to
      support the diverse needs and interests of students, and efforts to increase
      students' engagement and teach them skills to meet everyday challenges are
      proposed that begin long before students become disengaged from school.

PMID- 8267093
TI  - Institutional racism: an analysis of the mental health system.
AB  - Institutional racism is defined and its conceptual application to the institution
      of psychiatry and the mental health system is described. Data on changes in the
      patient population and the provision and utilization of mental health services
      since deinstitutionalization are examined. Mental health policy and diagnostic
      and treatment issues are identified as areas in which institutional racism
      affects minority groups.

PMID- 8267094
TI  - Stress in immigrant families with handicapped children: a child advocacy
      approach.
AB  - Poor immigrant families must cope with stress stemming from loss of home and
      adaptation to the host country. Those with handicapped children are also burdened
      with a parallel set of stressors in adapting to the handicap in an alien
      environment that may include a complex service system. Implications for practice
      are discussed with particular emphasis on advocacy to enhance delivery of
      services.

PMID- 8267095
TI  - Adolescent PTSD and developmental consequences of crack dealing.
AB  - The effect of crack dealing on emotionally disturbed adolescents in two African
      American inner-city communities is examined and illustrated by case examples.
      Crack dealing was most often found to have dynamics and consequences separate
      from those of crack use. These include post-traumatic stress disorder and other
      significant emotional disturbances arising from the violence associated with
      crack dealing, and the shaping of adolescent identity by the associated culture
      of violence and guns. Implications for school drug abuse education are explored.

PMID- 8267096
TI  - Toward an integrated theory of adolescent ego development: the "new look" at
      adolescent egocentrism.
AB  - The theoretical and empirical status of the traditional theory of adolescent
      egocentrism is examined and found wanting. An alternative theory is reviewed that
      reconceptualizes the ideational patterns of "egocentrism" as adaptational and
      coping functions of ego development, avoids anomalies found in the traditional
      theory, and promises a progressive research program.

PMID- 8267097
TI  - Adolescent mothers and repeated childbearing: effects of a school-based
      intervention program.
AB  - This study examined the effectiveness of a public school program for pregnant
      teenagers in preventing rapid repeated childbearing. Students permitted to attend
      longer than seven weeks postpartum were much more likely to avoid having another
      child in the next five years than were students required to return to their
      regular schools. The results indicate the potential of school-based programs to
      improve life outcomes for adolescent mothers and their children.

PMID- 8267098
TI  - Primary prevention of parenting dysfunction in high-risk cases.
AB  - Evaluation of high-risk cases treated via a tri-agency, interdisciplinary, early
      intervention program suggests that a better outcome was achieved in the treatment
      program than in a control group of similar high-risk families receiving standard
      care. The number of treated cases requiring child protection services decreased
      during treatment, and confirmed episodes of child abuse were fewer in the treated
      group than in the control group.

PMID- 8267099
TI  - Child maltreatment in family foster care.
AB  - Predictors of maltreatment of children living in family foster care were sought
      in characteristics of foster homes. Four characteristics that presented increased
      risk were identified: homes that had younger foster mothers, homes in which
      children shared bedrooms with other family members, homes about which case
      workers had reservations, and homes that were restricted for placement of certain
      children. Kinship-care homes were found to present decreased risk.

PMID- 8267100
TI  - Loneliness, depression, stress, and social supports in neglectful families.
AB  - Comparisons of neglectful with non-neglectful low-SES parents revealed that the
      neglectful parents reported more life stresses, greater depression and
      loneliness, and weaker informal social supports. In the neglectful families,
      loneliness was positively associated with life stresses and negatively associated
      with network supports, but not with caseworker-assessed social isolation.

PMID- 8267101
TI  - Adult attachment and adult child-older parent relationships.
AB  - Adult attachment status, concurrent and early relationships with parents, and
      depressive symptoms were assessed in 53 adults. Individuals with consistent
      reports of relationships--positive or negative--were most coherent in their
      narratives. Depressive symptoms were associated with negativity in both recalled
      and current relationships with parents, but were not correlated with coherence of
      narratives. Clinical implications of the findings are discussed.

PMID- 8267102
TI  - The battered woman syndrome: effects of severity and intermittency of abuse.
AB  - The concept of a battered woman syndrome was tested by assessing 50 battered
      women and 25 emotionally abused women who had recently left their relationships.
      For both groups, essential features of the syndrome were present and were
      significantly interrelated. Dynamic features of the prior abusive relationship
      correlated significantly with these sequelae. The concept of intermittency is
      proposed as an alternative to the cycle of violence theory as main contributor to
      the syndrome. Predictability of abuse was found to be unrelated to the
      intermittency measure.

PMID- 8267103
TI  - Cultural beliefs about rape and victims' response in three ethnic groups.
AB  - Cultural definitions of rape were assessed among 101 African-American, Hispanic,
      and non-Hispanic white female rape victims and 89 nonvictims matched for
      ethnicity, age, marital status, and socioeconomic status. Hispanics scored
      highest and whites lowest both in perceived community victim-blaming and in
      victims' psychological distress. Social and treatment implications are discussed.

PMID- 8267104
TI  - Ethnic differences in early adolescents' coping with school stress.
AB  - Three groups of early adolescents were compared on the prevalence and
      stressfulness of school-related events experienced during the transition to
      seventh grade, as well as on their individual coping behavior and the
      availability, extent, and type of social support they could mobilize.
      Implications for the development of intervention programs targeting minority
      adolescents are discussed.

PMID- 8267105
TI  - Why a White House Conference?

PMID- 8267106
TI  - An overview of sexual harassment.
AB  - OBJECTIVE: A few widely publicized cases have made sexual harassment a salient
      subject in the 1990s. This article reviews the topic in a comprehensive manner,
      with particular attention to demographic information, psychosocial consequences,
      appropriate therapeutic interventions, and related psychological issues. METHOD:
      Computerized literature searches were used to identify research and review papers
      from psychiatry and psychology journals. Nonscientific works that provide
      additional information are also cited. RESULTS: The literature suggests that
      sexual harassment is a widespread phenomenon, affecting 42% of women and 15% of
      men in occupational settings, 73% of women and 22% of men during medical
      training, and lower percentages in other educational settings. Despite the
      pervasive nature of this problem, only 1%-7% of victims file formal complaints.
      Sexual harassment produces an array of psychological and physical symptoms in
      over 90% of victims, and 12% seek help from mental health care professionals.
      Self-doubt is a central issue regardless of gender, but in instances where the
      perpetrator is male and the victim is female, there are ramifications unique to
      the trauma of gender-based abuse. It is critical that therapists avoid
      contributing to the process of "second injury" and not imply that patients have
      brought their troubles on themselves. Key therapeutic tasks include empathy,
      validation, and empowerment. CONCLUSIONS: Few experimental studies have focused
      on the victims of sexual harassment, and none have focused on the perpetrators.
      Psychiatry can play an invaluable role in the assessment and treatment of
      victims, the fostering of education and research in this area, and the
      understanding of underlying psychological and gender issues.

PMID- 8267107
TI  - Haptoglobin phenotypes and gene frequencies in unipolar major depression.
AB  - OBJECTIVE: Studies from the authors' laboratory have shown that major depression
      is accompanied by significantly increased plasma concentrations of positive acute
      phase proteins such as haptoglobin. Haptoglobin is characterized by a molecular
      variation with three known phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2). This study
      investigated haptoglobin plasma levels and phenotype and gene frequencies in
      unipolar major depression. METHOD: Haptoglobin plasma levels of 22 healthy
      volunteers, 32 patients with minor depression, and 72 patients with major
      depression were determined by means of a laser nephelometric method. Haptoglobin
      phenotyping of these 126 subjects and 200 healthy blood donors was also carried
      out. RESULTS: The patients with major depression exhibited significantly higher
      haptoglobin plasma levels than the healthy comparison subjects and the patients
      with minor depression. Subjects with the haptoglobin phenotype Hp 2-2 had
      significantly lower haptoglobin levels than the phenotype Hp 1-1 and Hp 2-1
      carriers. The frequencies of haptoglobin phenotypes Hp 2-1 (61.1%) and Hp 2-2
      (20.8%) in the patients with major depression were significantly higher and
      lower, respectively, than the frequencies in the normal population (i.e., the
      blood donors: 48.0% and 37.0%, respectively). The frequency of the Hp-1 gene was
      significantly greater in the patients with major depression (48.6%) than in the
      normal population (39.0%). CONCLUSIONS: Major depression is characterized by a
      hyperhaptoglobinemia that is largely independent of haptoglobin phenotypes. This
      altered distribution of haptoglobin phenotypes and genes suggests that genetic
      variation on chromosome 16 may be associated with that illness.

PMID- 8267108
TI  - Prenatal exposure to influenza and the development of schizophrenia: is the
      effect confined to females?
AB  - The question of whether prenatal exposure to influenza epidemics is associated
      with an increased risk of later schizophrenia remains controversial. The authors
      examined this relationship, using data on the dates of birth and gender of 3,827
      schizophrenic patients born in England and Wales between 1938 and 1965 and first
      admitted to hospitals in the 1980s, the numbers of live births between 1938 and
      1965, and the numbers of deaths attributed to influenza between 1937 and 1965.
      The analysis showed that females, but not males, exposed to influenza epidemics 5
      months before birth had a significantly greater rate of adult schizophrenia.

PMID- 8267109
TI  - Maintenance of training effects on the Wisconsin Card Sorting Test by patients
      with schizophrenia or affective disorders.
AB  - The authors used the Wisconsin Card Sorting Test to study 50 hospitalized
      psychiatric patients: 28 with schizophrenia, 17 with affective disorders, and
      five with schizoaffective disorder. The schizophrenic patients performed
      significantly more poorly than the patients with affective disorders. Both groups
      of patients improved when given additional instructions. The schizophrenic
      patients maintained their improvement when retested approximately 6 weeks later.
      The results suggest that factors other than frontal cortex dysfunction are
      involved in schizophrenic patients' performance on the Wisconsin Card Sorting
      Test.

PMID- 8267110
TI  - Serum concentrations of clozapine and its major metabolites: effects of
      cotreatment with fluoxetine or valproate.
AB  - Serum concentrations of clozapine, norclozapine, and clozapine-N-oxide were
      assayed in psychotic patients treated with clozapine alone (N = 17), clozapine
      with fluoxetine added (N = 6), or clozapine with valproic acid added (N = 11).
      Subjects were matched for age and other treatments, and concentrations were
      corrected for daily dose of clozapine (milligrams per kilogram of body weight).
      With valproic acid, there was a minor increase in total clozapine metabolites,
      which was even less with dose correction. Fluoxetine increased all clozapine
      analytes, in some cases to twice the levels in the subjects given only clozapine.

PMID- 8267111
TI  - A double-blind, placebo-controlled crossover study of ganglioside GM1 treatment
      for Alzheimer's disease.
AB  - In a double-blind trial, 12 patients with probable Alzheimer's disease were
      treated for 6 weeks with placebo and 6 weeks with monosialoganglioside (GM1) (100
      mg/day i.m.), which potentiates the actions of nerve growth factor. GM1 failed to
      produce significant improvement in patients' cognitive test performance,
      suggesting that this is not a viable approach to the treatment of cognitive
      deterioration in Alzheimer's disease.

PMID- 8267112
TI  - First-episode mania in late life.
AB  - Among 14 elderly patients (mean age = 74.6 years) with first-episode mania who
      were followed for 3 to 10 years, men had a higher risk of mortality. Compared to
      36 elderly patients with multiple episodes of mania, patients with first-episode
      mania were twice as likely to have a comorbid neurological disorder (71% [N = 10]
      versus 28% [N = 10]). Mania in the elderly appears to be a heterogeneous
      disorder.

PMID- 8267113
TI  - Prediction of reproductive status in women with bulimia nervosa by past high
      weight.
AB  - It is not understood why disturbed menstrual function occurs in as many as 50% of
      women with bulimia nervosa who are at normal weight. The authors measured
      luteinizing hormone (LH), estradiol, and progesterone in 13 women with bulimia
      nervosa who were at normal weight and six normal comparison subjects. They found
      that the women with bulimia nervosa were likely to have abnormal 24-hour
      luteinizing hormone (LH) secretion if their current weight was less than 85% of
      their past high weight.

PMID- 8267114
TI  - Unsuccessful suicide attempt by sertraline overdose.

PMID- 8267115
TI  - Panic attacks precipitated by sertraline.

PMID- 8267116
TI  - Dissociative symptoms in Japan.

PMID- 8267117
TI  - Fluoxetine-associated dystonia.

PMID- 8267118
TI  - Fluoxetine for obsessional symptoms in schizophrenia.

PMID- 8267119
TI  - Efficacy of the combination of buspirone and carbamazepine in early posttraumatic
      delirium.

PMID- 8267120
TI  - Buprenorphine for benzodiazepine-abusing heroin addicts.

PMID- 8267121
TI  - Tuberculosis and the severely mentally ill.

PMID- 8267122
TI  - Depression and poststroke mortality.

PMID- 8267123
TI  - Posttraumatic stress disorder and the insanity defense.

PMID- 8267124
TI  - Health insurance reform and psychotherapy.

PMID- 8267125
TI  - Cognitive remediation.

PMID- 8267126
TI  - Cognitive remediation.

PMID- 8267127
TI  - Predicting postcombat PTSD by using premilitary MMPI scores.

PMID- 8267128
TI  - Reparative therapy.

PMID- 8267129
TI  - Effects of clozapine on positive and negative symptoms in outpatients with
      schizophrenia.
AB  - OBJECTIVE: Clozapine is an atypical neuroleptic with superior efficacy in
      severely ill, treatment-resistant inpatients with schizophrenia. To determine if
      clozapine's differential efficacy generalizes to less ill, outpatients
      populations, the authors examined the effects of clozapine on positive and
      negative symptoms in outpatients with schizophrenia. METHOD: Outpatients with
      schizophrenia who had histories of partial response to conventional neuroleptics
      and who had not responded to a prospective 6-week trial of fluphenazine
      participated in a 10-week, double-blind, parallel-groups comparison of clozapine
      and haloperidol. Thirteen men and six women were given clozapine, and 15 men and
      five women were given haloperidol. Clinical response rates were determined and
      effects on primary versus secondary negative symptoms were addressed. Doses of
      clozapine and haloperidol at the end of the 10-week trial were 410.5 mg/day (SD =
      45.8) and 24.8 mg/day (SD = 5.5), respectively. RESULTS: Clozapine was superior
      to haloperidol for treating positive symptoms. In addition, eight of the patients
      given clozapine and only one of the patients given haloperidol fulfilled clinical
      responder criteria. Clozapine was also superior to haloperidol for treating
      negative symptoms, although these effects were relatively minor. Negative
      symptoms were significantly affected in the subgroup of patients with nondeficit
      schizophrenia but not in the subgroup with deficit schizophrenia. Overall,
      clozapine was well tolerated. CONCLUSIONS: Clozapine has superior efficacy for
      treating positive symptoms in partially responsive outpatients with chronic
      schizophrenia, suggesting that it has utility for a broad spectrum of patients
      with schizophrenia beyond the most severely ill.

PMID- 8267130
TI  - An epidemiologic, clinical, and family study of simple schizophrenia in County
      Roscommon, Ireland.
AB  - OBJECTIVE: The authors sought to estimate the prevalence of simple schizophrenia,
      compare the clinical presentations and courses of simple and "typical"
      schizophrenia, and examine psychopathology in first-degree relatives of probands
      with simple schizophrenia, probands with typical schizophrenia, and community
      comparison subjects. METHOD: The authors followed up all individuals with a
      recorded diagnosis of schizophrenia (N = 285) and 75% of those with a diagnosis
      of severe affective illness (N = 99) from the Roscommon County Case Register,
      which includes all individuals seeking psychiatric care in a rural county in
      western Ireland. The authors interviewed all available first-degree relatives of
      these groups and of matched unscreened community comparison subjects. RESULTS:
      Eleven cases of simple schizophrenia were diagnosed in the probands, for an
      estimated population prevalence and morbid risk in County Roscommon of 5.3 (SE =
      1.6) and 6.2 (SE = 1.9) per 10,000, respectively. Individuals with typical
      schizophrenia (N = 126) had more marked delusions, hallucinations, and positive
      thought disorder; individuals with simple schizophrenia had more pronounced
      negative thought disorder and a more chronic course. Neither social/occupational
      functioning nor negative symptoms differed between the two groups. The risks for
      schizophrenia and all nonaffective psychoses were greater in the relatives of the
      probands with simple schizophrenia than in the relatives of the community
      comparison subjects. CONCLUSIONS: In this sample, simple schizophrenia was
      relatively rare, was rather debilitating, and resembled typical schizophrenia in
      presentation and course except for the absence of positive psychotic symptoms.
      From a familial perspective, simple schizophrenia appears to be related to
      typical schizophrenia.

PMID- 8267131
TI  - Genetics, epidemiology, and the search for causes of schizophrenia.

PMID- 8267133
TI  - The neuropsychological signature of schizophrenia: generalized or differential
      deficit?
AB  - OBJECTIVE: The aim of this study was to provide a comprehensive assessment of
      neuropsychological functioning in schizophrenia so as to evaluate hypotheses of
      lateralized or differential cognitive impairment in this disorder. Furthermore,
      the study sought to address the potentially confounding factors of medication
      side effects and relevant demographic variables such as age, education, gender,
      and handedness. METHOD: The neuropsychological functioning of 28 schizophrenic
      patients whose medication had been withdrawn for research purposes and 15
      demographically matched normal subjects was evaluated. A comprehensive battery of
      tasks was used to determine whether performance patterns of schizophrenic
      patients were consistent with models of lateralized or localized
      neuropsychological impairment in schizophrenia. To facilitate comparison with
      results of other studies, several analytic strategies were used, including
      comparisons of group performance on individual tests, composite function scores,
      and evaluation of performance based on "clinical" criteria of impairment.
      RESULTS: In contrast to the normal subjects, the schizophrenic patients displayed
      impairment across measures of motor, sensory, and perceptual functioning, verbal
      and nonverbal memory, and indexes of frontal lobe functioning. This pattern of
      generalized dysfunction was evident regardless of the method of analysis used to
      assess performance. CONCLUSIONS: These findings fail to support conjectures
      regarding differential neurocognitive deficits in schizophrenia. However, the
      psychometric limitations of currently available neuropsychological measures may
      obscure the finding of differential impairment and must be considered in
      interpreting the results of this study as well as those of any investigation
      using such instruments.

PMID- 8267132
TI  - Relation of plasma fluphenazine levels to treatment response and extrapyramidal
      side effects in first-episode schizophrenic patients.
AB  - OBJECTIVE: The aim of this study was to determine the relation between plasma
      fluphenazine levels and clinical response in first-episode schizophrenic
      patients. METHOD: Data from 36 first-episode schizophrenic or schizoaffective
      inpatients diagnosed according to the Research Diagnostic Criteria were
      evaluated. The patients received open, standardized treatment with fluphenazine,
      20 mg/day, for at least 4 weeks. Psychopathology was assessed biweekly, and
      plasma fluphenazine levels were ascertained weekly. Patients were classified as
      responders or nonresponders, and correlations between their neuroleptic levels
      and ratings of psychopathologic and extrapyramidal symptoms were computed.
      RESULTS: Plasma fluphenazine levels for weeks 1 through 4 were significantly
      correlated with each other but were not correlated with age, gender, diagnosis,
      or race. Mean neuroleptic levels (weeks 3 and 4) were not different between
      responders and nonresponders and were not correlated with measures of
      psychopathology or extrapyramidal symptoms. CONCLUSIONS: These results do not
      indicate an association between plasma fluphenazine levels and response to
      treatment or extrapyramidal side effects in first-episode schizophrenia. The
      disparity between the results of this study and those of previous studies may be
      due to methodological differences or to a biologically based difference between
      first-episode and chronic patients.

PMID- 8267134
TI  - Effect of subtle neurological dysfunction on response to haloperidol treatment in
      schizophrenia.
AB  - OBJECTIVE: The primary purpose of this study was to assess whether an interaction
      between subtle neurological impairment and haloperidol plasma level affects
      treatment response and, if so, the impact on negative symptoms in particular.
      METHOD: Forty-three schizophrenic and two schizoaffective inpatients diagnosed
      according to Research Diagnostic Criteria were given, at the end of a 1-week
      placebo period, a baseline evaluation consisting of the Brief Psychiatric Rating
      Scale (BPRS), Scales for the Assessment of Positive and Negative Symptoms,
      Quantified Neurological Scale, and the Simpson-Angus Scale for extrapyramidal
      side effects. Subjects were randomly assigned to one of three haloperidol plasma
      ranges and treated for 6 weeks. At the end point the BPRS, Scales for the
      Assessment of Positive and Negative Symptoms, and Simpson-Angus Scale were
      readministered. Multiple linear regressions were used to assess the extent to
      which the interaction between neurological abnormality and haloperidol plasma
      level predicted the end-point symptoms once the baseline symptoms, neurological
      abnormality, and haloperidol plasma level were accounted for. RESULTS: Those
      patients with higher levels of overall abnormality on the Quantified Neurological
      Scale at baseline and with frontal dysfunction in particular, had, with
      increasing haloperidol plasma levels, more severe negative symptoms at end point.
      Neurological dysfunction was not related to end-point positive symptoms. The
      effect was specific to end-point negative symptoms and was independent of
      extrapyramidal side effects. CONCLUSIONS: If confirmed, these findings may
      indicate that relatively intact frontal function is needed for improvement in
      negative symptoms and that those patients with schizophrenia who have subtle
      neurological dysfunction should be treated with lower doses of neuroleptics.

PMID- 8267137
TI  - In memoriam. Howard P. Rome, M.D. 1910-1992.

PMID- 8267135
TI  - Preliminary application of magnetic resonance spectroscopy to investigate lactate
      induced panic.
AB  - OBJECTIVE: To characterize changes associated with lactate-induced panic, proton
      magnetic resonance spectroscopy (MRS) was used to measure brain lactate during
      intravenous infusion of 0.5-M sodium lactate in panic disorder patients and
      comparison subjects. METHOD: Eight panic disorder subjects, five medicated and
      three unmedicated, and eight healthy comparison subjects were studied at
      baseline, during lactate infusion (5 meq/kg over 20 minutes), and after infusion.
      Localized proton MRS was used to acquire averaged spectra every 5 minutes from a
      27-ml sampling volume in the insular cortex and adjacent regions. Brain lactate
      levels, quantitatively estimated in relationship to N-acetyl aspartate, were
      compared to blood lactate levels. RESULTS: The procedure was generally well
      tolerated; one panic subject requested early termination before lactate infusion.
      Significant rises in brain lactate levels occurred for all subjects during
      infusion. The panic patients who responded to lactate (N = 3) had significantly
      higher brain lactate levels before, during, and after infusion than did the
      comparison subjects (N = 8) and medicated patients who were lactate nonresponders
      (N = 4). After infusion the panic patients with lactate-induced panic exhibited a
      striking dissociation between decreasing blood lactate and further increases in
      brain lactate levels. CONCLUSIONS: These preliminary observations indicate that
      brain lactate increases during a standard lactate infusion. Lactate-induced panic
      is associated with greater increases than in comparison subjects and with
      prolonged elevations in brain lactate that are decoupled from falling blood
      lactate levels after completion of lactate infusion. Further investigation is
      necessary to clarify the mechanism(s) responsible for these findings and
      establish whether a causal relationship to the occurrence of lactate-induced
      panic exists.

PMID- 8267136
TI  - Panic disorder and gastrointestinal symptoms: findings from the NIMH
      Epidemiologic Catchment Area project.
AB  - OBJECTIVE: Clinical experience and recent reports suggest that there is a high
      prevalence of gastrointestinal symptoms in patients with panic disorder and that
      there is a high prevalence of panic disorder in patients with irritable bowel
      syndrome, a functional gastrointestinal disorder. To assess gastrointestinal
      symptoms in a nonpatient, community-based sample, the authors surveyed the
      prevalence of gastrointestinal symptoms in individuals with panic disorder and
      other or no psychiatric disorders obtained in a national community survey.
      METHOD: Subjects were 13,537 respondents at four sites of the National Institute
      of Mental Health (NIMH) Epidemiological Catchment Area project. DSM-III diagnoses
      were determined by using the NIMH Diagnostic Interview Schedule (DIS).
      Gastrointestinal symptoms were assessed from the somatization disorder section of
      the DIS. RESULTS: Individuals with panic disorder had a significantly higher rate
      of endorsing gastrointestinal symptoms, including those typically associated with
      irritable bowel syndrome, than those with other or no psychiatric diagnosis.
      CONCLUSIONS: Findings suggest a diagnostic overlap between panic disorder and
      irritable bowel syndrome, with similar demographic and clinical characteristics
      of patients. Limitations of the study are discussed in terms of medical
      assessment and self-report inventories. Practical and theoretical implications
      are discussed.

PMID- 8267138
TI  - Impact of the Gulf War on the anxiety, cortisol, and growth hormone levels of
      Israeli civilians.
AB  - OBJECTIVE: The authors investigated the impact of continuous and repeated stress
      on Israeli civilians exposed to missile attacks during the Gulf War. METHOD:
      Study 1 included 26 healthy volunteers aged 28-59 years. Their scores on the
      Hamilton Anxiety Rating Scale and levels of plasma cortisol and growth hormone
      (GH) were evaluated before, during, and after the war. Study 2 included 13
      healthy volunteers aged 25-59 years. Their scores on the state portion of the
      State-Trait Anxiety Inventory and levels of cortisol and GH were measured three
      times daily (8:00 a.m., noon, and 6:00 p.m.) at two time points (during and after
      the war). RESULTS: Anxiety levels of civilians exposed to the threat of war and
      later to actual missile attacks were significantly higher before and during the
      war than afterward. Anxiety during the war reached a peak in the evening. The
      increase in anxiety was not accompanied by any change from basal morning cortisol
      and GH levels or by diurnal variations in these hormones. CONCLUSIONS: Anxiety
      levels during the war were similar to those 1 day before its onset, which can be
      explained by the nature of coping processes. During the war, anxiety levels were
      highest in the evening, reflecting the war routine (missile attacks occurred
      mostly at night). The unaltered hormone levels and their normal diurnal
      variations despite the subjects' persistent anxiety were probably due to
      adaptation of the hypothalamic-pituitary-adrenal and hypothalamic-somatotropin
      axes to continuous stress.

PMID- 8267139
TI  - Psychological effects of torture: a comparison of tortured with nontortured
      political activists in Turkey.
AB  - OBJECTIVE: The aim of the study was to investigate the long-term effects of
      torture in a group of former political prisoners. METHOD: The study was carried
      out in Istanbul, Turkey, where 55 Turkish political activists who had been
      tortured were compared with a closely matched group of 55 activists who had not
      been tortured. The Structured Clinical Interview for DSM-III-R, the
      Semistructured Interview for Survivors of Torture, and other self-rated and
      assessor-rated measures of anxiety, depression, and posttraumatic stress disorder
      (PTSD) were used. The tortured and the nontortured activists were similar in age,
      sex, marital and socioeconomic status, political ideology, political involvement,
      stressful life events other than torture, and other features. RESULTS: The
      torture survivors reported an average of 291 exposures to a mean of 23 forms of
      torture. The mean length of their imprisonment was 47 months. The survivors of
      torture had significantly more symptoms of PTSD and anxiety/depression than the
      nontortured comparison subjects, although their PTSD symptoms were only
      moderately severe and their general mood was normal. Despite the severity of
      their torture experiences, the survivors had only a moderate level of
      psychopathology. CONCLUSIONS: The results suggest that torture has long-term
      psychological effects independent of those related to uprooting, refugee status,
      and other traumatic life events in a politically repressive environment. Prior
      knowledge of and preparedness for torture, strong commitment to a cause,
      immunization against traumatic stress as a result of repeated exposure, and
      strong social supports appear to have protective value against PTSD in survivors
      of torture.

PMID- 8267140
TI  - Posttraumatic stress disorder in survivors of a mass shooting.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) has been best studied among
      combat veterans. Less is known about PTSD among civilian populations exposed to
      traumatic events. A recent mass murder spree by a gunman in a cafeteria in
      Killeen, Tex., has provided a unique opportunity to study acute-phase civilian
      responses to a combat type of experience. METHOD: Approximately 1 month after the
      disaster, 136 survivors were interviewed with the Diagnostic Interview
      Schedule/Disaster Supplement. RESULTS: In the acute postdisaster period, 20% of
      the men and 36% of the women met criteria for PTSD, which was the most prevalent
      psychiatric disorder. Most subjects who developed PTSD had no history of
      psychiatric illness. Rates of preexisting PTSD were relatively high and did not
      predict the presence of PTSD after the disaster. A history of other predisaster
      psychiatric disorders predicted postdisaster PTSD in women but not in men. One
      half of the women and one-fourth of the men with postdisaster PTSD also met
      criteria for another postdisaster psychiatric diagnosis, especially major
      depression. Psychopathology was infrequent in subjects without PTSD. CONCLUSIONS:
      Disaster intervention workers may be able to most effectively use limited mental
      health provider resources in the acute postdisaster period by focusing on
      screening for acute PTSD, which will identify the majority of cases with
      psychiatric disorders following this kind of disaster. Survivors who have no
      history of psychiatric disorder should be screened along with those who do
      because in the present study, they represented the majority of the PTSD cases.
      Subjects with a history of major depression and women with preexisting
      psychopathology may be especially vulnerable to posttraumatic syndromes.
      Individuals with PTSD should be further examined for additional psychiatric
      diagnoses that may complicate recovery, especially major depression. PTSD among
      survivors of civilian combat-like experiences does not appear to present in the
      same way that it has been described in Vietnam veterans.

PMID- 8267141
TI  - Professional practice patterns of U.S. psychiatrists.
AB  - OBJECTIVE: The authors develop a classification of psychiatric practice based on
      primary and secondary work settings. METHOD: Data from the 1988-1989 APA
      Professional Activities Survey were used to characterize seven practice groups:
      public psychiatrists, public psychiatrists with private secondary work settings,
      private psychiatric/general hospital psychiatrists, private office practice
      psychiatrists, private office practice psychiatrists with secondary private
      psychiatric/general hospital work settings, private office practice psychiatrists
      with secondary settings other than private hospitals, and psychiatrists in
      private organized outpatient settings. Psychiatrists primarily in government
      administrative agencies, medical schools, or nursing homes were among those
      excluded. Usable data were available from 16,135 psychiatrists (82.8% of the
      target respondents). RESULTS: The largest groups were private psychiatric/general
      hospital psychiatrists (19.6%), private office practice psychiatrists with
      secondary settings other than private hospitals (18.9%), and private office
      practice psychiatrists with secondary private psychiatric/general hospital work
      settings (17.4%), followed by public psychiatrists with private secondary work
      settings (14.5%), private office practice psychiatrists (11.7%), public
      psychiatrists (11.4%), and psychiatrists in private organized outpatient settings
      (6.6%). During a typical week, the practice groups varied in the average
      proportion of their outpatients who received assessments, therapy and medication,
      therapy and no medication, and medication management. The groups also varied in
      the mean number of patients they treated each month with affective disorders,
      schizophrenia, anxiety disorders, and other disorders. CONCLUSIONS: Only about
      one in 10 clinical psychiatrists is engaged exclusively in office-based private
      practice, and approximately half of the outpatients treated by the average
      psychiatrist receive medication. Work setting appears to exert a powerful
      influence over whom psychiatrists treat and what services they provide. Because a
      majority of psychiatrists work in more than one setting, most psychiatrists serve
      a broad range of patients and provide a variety of treatments.

PMID- 8267143
TI  - Cumulative index to The American Journal of Surgical Pathology. 1977-1993.
      Volumes 1-17.

PMID- 8267142
TI  - Sex differences in psychiatrists' practice patterns and incomes.
AB  - OBJECTIVE AND METHOD: Using data from the APA's 1988-1989 Professional Activities
      Survey, the authors compared male and female psychiatrists on demographic
      characteristics, training, practice patterns, and income. RESULTS: In keeping
      with previous studies' findings, female respondents on the average were younger
      than male respondents and more likely to have taken a residency or fellowship in
      child or adolescent psychiatry, worked fewer hours per week, allocated their
      working hours differently among types of activities, saw fewer patients per week,
      and worked in somewhat different settings. Multiple regression analysis showed
      that women had significantly lower mean net annual income than men after the
      effects of those predictors were statistically controlled. CONCLUSIONS:
      Differences in age, training, hours worked in specific settings, and numbers of
      patients do not completely account for the gender gap in psychiatrists' annual
      incomes.

PMID- 8267144
TI  - The International Anesthesia Research Society and the Society of Cardiovascular
      Anesthesiologists: a new partnership.

PMID- 8267145
TI  - The effect of ephedrine bolus administration on left ventricular loading and
      systolic performance during high thoracic epidural anesthesia combined with
      general anesthesia.
AB  - We investigated the effect of ephedrine on left ventricular function in patients
      without cardiovascular disease under high thoracic epidural anesthesia combined
      with general anesthesia. Because the epidural block was extended to all cardiac
      segments, ephedrine was assumed to be deprived of its centrally mediated actions.
      Left ventricular (LV) function was assessed using transesophageal
      echocardiography. We measured arterial pressure (AP), heart rate (HR), LV end
      systolic and end-diastolic diameter and area (ESA, EDA), wall thickness, and LV
      ejection time before and after intravenous ephedrine bolus administration. We
      calculated area ejection fraction (EFA), end-systolic wall stress (ESWS), and
      mean velocity of circumferential fiber shortening (mVcfc). Ephedrine had a
      biphasic effect on left ventricular function. It transiently decreased EDA from
      18.9 to 16.5 cm2 (mean), whereas EFA and mVcfc were increased from 33% to 49%,
      and from 1.88 to 2.67 circumferences/s, respectively. During the second phase,
      ephedrine increased mean arterial pressure (MAP) from a baseline value of 62 to
      87 mm Hg, EDA was restored to 19.3 cm2, and EFA and mVcfc remained above baseline
      (52% and 2.64 circumferences/s, respectively). ESWS was not significantly
      increased from baseline. We conclude that ephedrine improves left ventricular
      contractility, even in the presence of high thoracic epidural anesthesia, without
      causing relevant changes of left ventricular afterload.

PMID- 8267146
TI  - Comparisons of tetracaine spinal anesthesia with clonidine or phenylephrine in
      normotensive and hypertensive humans.
AB  - To compare the hemodynamics and anesthetic effects of spinal tetracaine
      containing either clonidine or phenylephrine administered to normotensive or
      hypertensive patients, we studied 75 patients allocated to one of three groups,
      each of which included nine hypertensive patients: clonidine group (n = 25)
      received 2 mL of 0.5% tetracaine (10 mg) containing clonidine (0.15 mg);
      phenylephrine group (n = 25) received 2 mL of 0.5% tetracaine (10 mg) containing
      phenylephrine (3 mg); and control group (n = 25) received 2 mL of 0.5% tetracaine
      (10 mg) alone. Analgesic levels and the intensity of motor block obtained did not
      differ significantly among the three groups. However, the regression of sensory
      block (skin dermatome) was significantly slower in patients given clonidine (T9
      +/- 3) or phenylephrine (T9 +/- 3) at 300 min after the injection than in those
      (L1 +/- 3) in the control group (P < 0.01). Between normotensive and hypertensive
      patients, there was no significant difference in sensory and motor block in the
      three groups. Mean blood pressure (MBP) in both hypertensive and normotensive
      patients given tetracaine-clonidine remained approximately 20% lower than that in
      the control group for as long as 7 h after the injection (P < 0.05). We conclude
      that the inclusion of clonidine can provide similar effects to that of
      phenylephrine with respect to prolongation of hyperbaric tetracaine spinal
      anesthesia, but could cause more hypotension, without bradycardia, in both
      normotensive and hypertensive patients for a prolonged time (i.e., 420 min).

PMID- 8267147
TI  - Glomus tumors of the head and neck: anesthetic considerations.

PMID- 8267148
TI  - Perioperative care of the liver transplant patient: Part 1.

PMID- 8267149
TI  - Predictive and diagnostic tests of renal failure: a review.
AB  - Postoperative acute renal insufficiency is a discouraging complication with a
      mortality rate that remains persistently high, despite improved techniques of
      dialysis and advances in the perioperative management of hemodynamic, metabolic,
      and infective complications. A complete understanding of the role of renal
      hemodynamics in the pathophysiology of acute renal failure still has not emerged.
      Serial determination of creatinine clearance is currently the most sensitive test
      for predicting the onset of perioperative renal dysfunction; however, the test is
      not practical for measuring renal function under operating room conditions.
      Furthermore, testing creatinine clearance is time-consuming, labor intensive, and
      may cause significant delay in identifying the onset of renal dysfunction. That
      early therapy modifies the prognosis of renal dysfunction remains an untested
      hypothesis until a measurement that predicts renal outcome is found that is
      sensitive, specific, and easily obtainable. The ability to measure intrarenal
      blood flow distribution may offer promise for improving our predictive and
      diagnostic abilities to assess perioperative acute renal failure. Methodologic
      constraints, however, limit the practicality of this measurement in the
      perioperative setting at this time. Instead, we rely on indirect variables that
      do not bear a reliable relationship to glomerular filtration rate and renal
      function.

PMID- 8267150
TI  - Association of preoperative risk factors with postoperative acute renal failure.
AB  - We performed a systematic review of 28 studies that examined preoperative risk
      factors for postoperative renal failure. Included in the studies were 10,865
      patients who underwent either vascular, cardiac, general, or biliary surgery. No
      two studies used the same criteria for acute renal failure. Variability in
      definitions of renal failure, lack of consistent criteria for establishing risk
      factors, and nonuniformity in the statistical methods employed result in a
      literature that is not adequate to support a comprehensive quantitative review.
      Of the 30 variables considered in the studies, preoperative renal risk factors,
      such as increased serum creatinine, increased blood urea nitrogen, and
      preoperative renal dysfunction were repeatedly found to predict postoperative
      renal dysfunction. The literature provides little quantitative information
      concerning the degree of risk associated with other factors. Cardiac risk
      factors, such as left ventricular dysfunction, were reported to be predictive of
      postoperative renal failure more consistently than was advanced age.

PMID- 8267151
TI  - Syringe pumps for infusion of vasoactive drugs: mechanical idiosyncrasies and
      recommended operating procedures.
AB  - Syringe pumps for vasoactive infusions have the advantages of small size and
      weight, portability, and low cost of the disposable components. However, limited
      syringe capacity necessitates the use of high drug concentrations, and the
      accidental delivery of even a small volume of infusate could seriously alter the
      patient's hemodynamics. To determine the circumstances under which drug delivery
      might be delayed, or inadvertent boluses could be delivered into the manifold,
      two brands of commercially available clinical syringe pumps were connected to a
      stopcock manifold via small-bore tubing and a series of tests were performed.
      When the syringe pumps were operated at 3 mL/h against a closed stopcock, the
      pumps' occlusion alarms did not sound for 18-22 min, and when the stopcock
      subsequently was opened, 0.6-0.9 mL of infusate was delivered as a bolus.
      Elevating the syringe pump by 120 cm resulted in the delivery of up to 0.5 mL of
      infusate with the pump turned off. When a syringe pump operating at 6 mL/h was
      turned off, typically an additional 0.05 mL was delivered during the ensuing 2-3
      min. Depending upon the method used to flush the tubing prior to use, delays in
      drug delivery of 2-3 min occurred at an infusion rate of 3 mL/h. These
      observations emphasize the need for careful equipment setup and proper use of the
      manifold stopcocks to avoid unintended drug administration or delay in drug
      administration.

PMID- 8267152
TI  - Intended epidural anesthesia as possible cause of cauda equina syndrome.

PMID- 8267153
TI  - Pneumothorax as a consequence of thoracic subarachnoid block.

PMID- 8267154
TI  - Transient median nerve palsy after general anesthesia: does res ipsa loquitur
      apply?

PMID- 8267155
TI  - Severe sensory deficits with preserved motor function after removal of a spinal
      arteriovenous malformation: correlation with simultaneously recorded
      somatosensory and motor evoked potentials.

PMID- 8267156
TI  - Anesthesia in a neonate with tamponade due to massive pericardial effusion.

PMID- 8267157
TI  - Mechanisms of the inhibitory effect of ketamine on guinea pig isolated main
      pulmonary artery.
AB  - Although ketamine increases pulmonary vascular resistance of patients, an
      occasional decrease of resistance in animals and humans has been reported. In
      addition, ketamine has a direct relaxant effect on isolated smooth muscle. The
      effects of ketamine on the main pulmonary artery rings isolated from the guinea
      pig were studied to elucidate the underlying mechanism of the reported relaxant
      effect of this anesthetic on smooth muscle. Ketamine (10-250 micrograms/mL)
      caused a concentration-dependent shift to the right of CaCl2 concentration-effect
      curves on artery rings, suggesting an interference with Ca2+ metabolism. In
      Ca(2+)-free buffer, ketamine (10-250 micrograms/mL) did not affect the magnitude
      of epinephrine-induced contractions but inhibited dose-dependent BaCl2-induced
      contractions. These observations suggest that ketamine inhibits transmembrane
      Ca2+ influx but does not affect its release from intracellular stores or its
      binding to intracellular receptor sites on the contractile system. Ketamine (25
      500 micrograms/mL) also caused equipotent concentration-dependent relaxation of
      epinephrine-induced contractions in the absence and the presence of monensin, a
      Na(+)-ionophore that dissipates the Na+ gradient across the cell membrane, and in
      Na(+)-free, sucrose-substituted buffer. Ketamine (25-500 micrograms/mL) also
      relaxed ouabain-induced contractions to the baseline, an effect that was
      significantly attenuated in the presence of ruthenium red, a Ca2+ adenosine
      triphosphatase (ATPase) inhibitor. The relaxant effect of ketamine (250-750
      micrograms/mL) of epinephrine-induced contraction also was attenuated in the
      presence of 0.1 mM lanthanum chloride (La3+), an inhibitor of adenosine 5'
      triphosphate (ATP)-dependent Ca2+ extrusion, and completely inhibited in the
      presence of 10 mM La3+.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267158
TI  - Anesthetic management of children with intracardiac extension of abdominal
      tumors.

PMID- 8267159
TI  - Pregnancy complicated by preeclampsia and adrenal insufficiency.

PMID- 8267160
TI  - Cardiac failure after orthotopic liver transplantation.

PMID- 8267161
TI  - Suspected protamine allergy: diagnosis and management for coronary artery
      surgery.

PMID- 8267162
TI  - Arytenoid dislocation with lighted stylet intubation: case report and
      retrospective review.

PMID- 8267163
TI  - Use of a stylet with the aged laryngeal mask airway?

PMID- 8267164
TI  - Review reviewed.

PMID- 8267165
TI  - Another source of potential medication administration error.

PMID- 8267166
TI  - Impact of isoflurane and N2O on cerebrospinal fluid pressure.

PMID- 8267167
TI  - Application of airline pilots' hours to trainee anesthesiologists.

PMID- 8267168
TI  - Tuffier's line: the normal distribution of anatomic parameters.

PMID- 8267169
TI  - An unusual cause of airway obstruction.

PMID- 8267170
TI  - Use of muscle relaxants for electroconvulsive therapy: how much is enough?

PMID- 8267171
TI  - Administration of O2 in patients with critical coronary artery disease.

PMID- 8267172
TI  - Video-assisted fiberoptic endotracheal intubation.

PMID- 8267173
TI  - Internal jugular vein cannulation.

PMID- 8267174
TI  - Propofol and epilepsy: time to clarify!

PMID- 8267175
TI  - Fentanyl or alfentanil decreases the minimum alveolar anesthetic concentration of
      isoflurane in surgical patients.
AB  - The minimum alveolar anesthetic concentration (MAC) is an accepted potency
      measure for inhaled anesthetics. There is no generally accepted intraoperative
      measure of opioid potency, partly because of the difficulty in obtaining steady
      state biophase concentrations. We have studied the relative potency of fentanyl
      and alfentanil by using computer-assisted continuous infusions (CACI), in terms
      of reduction of isoflurane MAC. Data are presented from 79 patients in whom
      anesthesia was induced with thiopental and maintained with a CACI of fentanyl
      (set to achieve a plasma concentration of 0, 1, 3, 6, or 8 ng/mL) or alfentanil
      (0, 70, 210, 400, or 1000 ng/mL) with a predetermined end-tidal concentration of
      isoflurane. A determination of movement in response to skin incision was made.
      Without any opioid, the MAC of isoflurane was 1.25%. The maximum likelihood
      solution to a logistic regression model showed that fentanyl 0.5 ng/mL (95%
      confidence intervals [CI], 0-4.6 ng/mL) or alfentanil 28.8 ng/mL (95% CI, 0-70.9
      ng/mL) resulted in a 50% isoflurane MAC reduction. In the logistic regression
      model, age or weight were not significant factors in the model. These results
      suggest that the comparative intraoperative potency ratio for alfentanil and
      fentanyl is 58:1, and that this methodology allows for direct intraoperative
      comparisons of opioid potency.

PMID- 8267176
TI  - Coagulation tests, blood loss, and transfusion requirements in platelet-rich
      plasmapheresed versus nonpheresed cardiac surgery patients.
AB  - The results of several studies suggest that acute platelet-rich plasmapheresis
      decreases blood loss and allogeneic blood product transfusion requirements in
      cardiac surgery patients. We designed a randomized, prospective study to
      determine whether acute platelet-rich plasmapheresis decreases blood loss and
      allogeneic transfusion requirements in primary cardiac surgery patients. Forty
      patients were randomized to a control or pheresis group. The pheresis group had
      platelet-rich plasmapheresis performed before cardiopulmonary bypass (CPB) and
      the platelet-rich plasma (PRP) was returned after CPB. The control group was
      managed in the normal fashion without pheresis. All patients had serial
      coagulation studies, hemoglobin, and platelet counts determined intra- and
      postoperatively. Chest tube drainage and transfusion requirements were recorded.
      There were no differences in the coagulation tests, platelet counts, chest tube
      drainage, or allogeneic blood product transfusion requirements between the two
      groups at any time. The authors conclude that the use of acute platelet-rich
      plasmapheresis in primary cardiac surgery patients does not decrease chest tube
      drainage or the need for allogeneic blood transfusions.

PMID- 8267177
TI  - Last round for a "heavyweight"?

PMID- 8267178
TI  - Combined epidural analgesia and general anesthesia induce ischemia distal to a
      severe coronary artery stenosis in swine.
AB  - Epidural analgesia combined with general anesthesia may improve cardiac function
      and reduce the work of the heart by decreasing the rate pressure product.
      However, the effect of this combined technique has not been studied in the
      presence of severe coronary artery stenosis. Therefore, we investigated epidural
      analgesia combined with general anesthesia in a swine model with a tight coronary
      artery stenosis. The coronary stenosis placed around the proximal left anterior
      descending coronary artery (LAD) allowed normal blood flow at rest but only
      minimum hyperemia in response to the coronary dilator, adenosine. To accomplish
      an extensive sympathetic block, we injected enough bupivacaine 0.5% into the
      lumbar epidural space to reach at least the level of the first thoracic vertebra
      (T1). Epidural catheter position was verified by fluoroscopy. Hemodynamic
      changes, LAD myocardial blood flow, and regional myocardial wall thickening were
      measured. Fifteen minutes after the injection of bupivacaine, systolic and
      diastolic blood pressure decreased 24.1% and 26%, respectively, cardiac output
      decreased 25.6%, and mean coronary blood flow decreased 42%, compared to the
      saline control. Myocardial wall thickening in the LAD bed decreased 31%, although
      it remained unchanged in the normal myocardium. Epidural bupivacaine added to
      general anesthesia resulted in moderate hypotension. Distal to the coronary
      stenosis was a moderate decrease in regional myocardial function and a severe
      reduction in blood flow.

PMID- 8267179
TI  - A comparison of systolic blood pressure variations and echocardiographic
      estimates of end-diastolic left ventricular size in patients after aortic
      surgery.
AB  - As suggested by experimental studies, systolic pressure variation (SPV), the
      difference between maximum and minimum values of systolic blood pressure after a
      single positive pressure breath, may be a fair indicator of left ventricular
      preload. SPV was quantified in 21 patients who had undergone abdominal aortic
      surgery and were sedated under mechanical ventilation. The aim of the study was
      to assess the ability of this parameter to qualitatively estimate left
      ventricular preload measured using transesophageal echocardiography. All patients
      had preoperative radionuclide ejection fraction > 45%. Postoperative mechanical
      ventilatory patterns were the same for all patients: tidal volume = 10 mL/kg;
      respiratory frequency = 12-14 breaths/min; and zero end-expiratory pressure mode.
      Left ventricular dimensions at end-diastole correlated well with the magnitude of
      both SPV (r = 0.80) and its delta down (dDown) component (i.e., the degree by
      which systolic pressure decreases with each mechanical breath) (r = 0.83). Once
      the first measurement was completed, volume loading with two increments of 250 mL
      of human albumin 5% was performed in all but three patients. Each volume loading
      step caused a significant increase in the end-diastolic area (EDa) index (7.0 +/-
      1.6 to 8.5 +/- 1.6 cm2/m2) and cardiac index (CI) (3.1 +/- 0.9 to 4.1 +/- 0.9
      L.min-1 x m-2) and a concomitant significant decrease in the SPV (8.6 +/- 4.5 to
      6.1 +/- 3.7 mm Hg) and its dDown component (5.9 +/- 4.1 to 2.9 +/- 2 mm
      Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267180
TI  - Multicenter study versus nausea outcomes: the value of large numbers and the
      limitations.

PMID- 8267181
TI  - Response of cerebrospinal fluid pressure to continuous positive airway pressure
      in volunteers.
AB  - The effect of a 10-min period of continuous positive airway pressure (CPAP) of 12
      cm H2O on lumbar cerebrospinal fluid pressure (CSFP), cerebral perfusion pressure
      (CPP), central venous pressure (CVP), mean arterial pressure (MAP), heart rate
      (HR), and end-tidal carbon dioxide (ETCO2) was studied in eight volunteers. CSFP
      increased (7 +/- 4 control vs 11 +/- 4 mm Hg; P < 0.001; mean +/- SD) and CVP
      increased (2 +/- 2 control vs 5 +/- 3 mm Hg; P < 0.001; mean +/- SD) when CPAP of
      12 cm H2O was applied. CPP decreased slightly during CPAP (79 +/- 13 vs 74 +/- 19
      mm Hg; P < 0.05; mean +/- SD), whereas MAP, HR, and ETCO2 remained unchanged. The
      findings of our study suggest that changes in CSFP and CPP due to moderate levels
      of CPAP, although statistically significant, are probably of only minor clinical
      importance.

PMID- 8267182
TI  - Effect of mannitol on cerebrospinal fluid dynamics and brain tissue edema.
AB  - Mannitol is used widely to decrease intracranial pressure (ICP); however, the
      mechanism by which this effect occurs is unclear. This study was designed to
      examine the effects of mannitol on cerebrospinal fluid (CSF) formation rate (Vf),
      resistance to reabsorption of CSF (Ra), and brain tissue water content (BTWC).
      Eighteen New Zealand White rabbits were allocated into one of three groups and
      studied at baseline and at two sequential doses of 20% mannitol: 0.75 g/kg
      followed by 4.4 mg.kg-1.min-1, and 2.0 g/kg (1.25 g/kg added to the initial dose
      of 0.75 g/kg) followed by 8.6 mg.kg-1.min-1. In Group 1, closed
      ventriculocisternal perfusion (VCP) was performed to determine changes in ICP due
      to mannitol. In Group 2, the increase in CSF osmolality due to mannitol was
      determined. In Group 3, mock CSF was used for open VCP to determine Vf and Ra. At
      the conclusion of each study, brain tissue samples were taken for determination
      of BTWC. Mannitol increased CSF and plasma osmolality. Ra was increased by 104%
      with the low dose of mannitol and not significantly changed by the high dose.
      Mannitol decreased BTWC, Vf (by 49% with the high dose), ICP, and hematocrit. The
      authors conclude that two of the mechanisms contributing to decreased ICP with
      mannitol are: 1) decreased CSF volume as indicated by decreased Vf, and 2)
      decreased brain tissue volume as indicated by decreased BTWC.

PMID- 8267183
TI  - The postoperative interview: assessing risk factors for nausea and vomiting.
AB  - Most studies of postoperative nausea and vomiting have concentrated on single
      etiologic factors and have not detailed the method of assessing these symptoms.
      This study used postoperative interview data from patients at four teaching
      hospitals during 1988-89, to determine 1) risk factors for nausea/vomiting, 2)
      whether the type of surgery affected the rate of nausea/vomiting among female
      patients, 3) whether differences in rates across hospitals were due to
      differences in patient case-mix, and 4) whether there were differences in the
      rate of nausea/vomiting among the patients of individual anesthesiologists.
      Research nurses performed 16,000 interviews (59% of all inpatients) from a closed
      question standardized format. With a multiple logistic regression that controlled
      simultaneously for all risk factors, factors associated with increased risk for
      nausea/vomiting for all patients included younger age, female, lower physical
      status score, no preoperative medical conditions, nonsmokers, elective
      procedures, longer duration of anesthesia, inhaled anesthetics, use of
      intraoperative opioids, and gynecologic or ophthalmologic operations. Among
      women, risk factors were similar, with minor gynecologic surgery associated with
      increased risk (relative odds = 2.30). We found marked variations in the rate of
      nausea/vomiting across hospitals (range, 39% to 73%), and these variations were
      not explained by the case-mix of patients. The rate of nausea/vomiting varied
      substantially across anesthesiologists in each hospital and the differences were
      not explained by differences in the patients they managed. Thus in the time
      period immediately preceding the introduction of newer antiemetic drugs, we found
      that the rates of this common problem were persistently high as perceived from
      the patients' point of view.

PMID- 8267184
TI  - Effect of etomidate on in vivo ischemia-induced dopamine release in the corpus
      striatum of the rat: a study using cerebral microdialysis.
AB  - Dopamine (DA) is released in large quantities into the corpus striatum during
      cerebral ischemia and may exacerbate tissue damage. Using cerebral microdialysis,
      we studied the effect of etomidate on in vivo ischemia-induced DA release in rat
      corpus striatum. Reversible cerebral ischemia was induced by using carotid
      ligatures and hypovolemic hypotension, and monitored with laser Doppler
      flowmetry. After baseline measurements, 20 normothermic, anesthetized rats were
      subjected to three separate periods of cerebral ischemia, interrupted by 45- to
      75-min periods of reperfusion. The rats were randomized into two groups. All rats
      received 400 mg/kg of intraperitoneal chloral hydrate for induction of
      anesthesia. In Group I (n = 10) anesthesia was maintained using additional
      intraperitoneal chloral hydrate 100 mg/kg every 2 h. Group II received etomidate
      0.6 mg/kg 10 min before the first episode of cerebral ischemia, followed by an
      infusion of 60 micrograms.kg-1 x min-1. Before each subsequent period of induced
      ischemia, an additional dose of etomidate (0.6 mg/kg) was administered. DA levels
      were approximately 350 times above baseline in Group I during the three ischemic
      episodes (IS1, IS2, and IS3). In Group II, ischemia-induced DA release was
      significantly attenuated (by 79%) during IS1, IS2, and IS3 compared to Group I (P
      < 0.01). DA levels did not significantly change in magnitude during the three
      ischemic episodes in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267185
TI  - Middle cerebral arterial blood flow velocity increases during laparoscopic
      cholecystectomy.
AB  - The effects of intraperitoneal CO2 insufflation on middle cerebral arterial blood
      flow velocity were evaluated in 10 patients undergoing laparoscopic
      cholecystectomy under general anesthesia with nitrous oxide, oxygen, and
      isoflurane. Blood flow velocity was measured using transcranial Doppler
      ultrasonography. During CO2 insufflation, Paco2 and the end-tidal CO2
      concentration (PETCO2) increased significantly compared with the preinsufflation
      baseline value (P < 0.01) while ventilation was kept constant. Cerebral blood
      flow velocity also increased significantly in comparison with the baseline value
      (P < 0.01). These values still exceeded baseline values 10 min after deflation of
      the peritoneal cavity. A significant positive correlation was observed between
      blood flow velocity and Paco2 (P < 0.001). Our results suggest that
      intraperitoneal CO2 insufflation during laparoscopic cholecystectomy increases
      cerebral blood flow and that this is probably due to an increased Paco2.

PMID- 8267186
TI  - Prophylactic effects of pirenzepine (M1-blocker) on intraoperative stress ulcer:
      comparison with an H2-blocker.
AB  - Patients under general anesthesia were treated with either an H2-blocker,
      ranitidine 50 mg, or an M1-blocker, pirenzepine 10 mg, and the effects of the two
      drugs on the gastric mucosa were compared by the measurement of the gastric juice
      pH and viscosity. The results showed that pirenzepine increased the gastric juice
      pH sufficiently while maintaining the gastric juice viscosity, and that
      ranitidine maintained the gastric juice pH higher than pirenzepine while
      decreasing the gastric juice viscosity. These results suggest that treatment with
      pirenzepine may have advantages in the prevention of stress ulcers.

PMID- 8267187
TI  - Effects of nimodipine on regional blood flow in heart and brain during
      cardiopulmonary resuscitation in pigs.
AB  - The effect of nimodipine on organ blood flow during cardiopulmonary resuscitation
      (CPR) was studied in 26 anesthetized pigs. After 5 min of ventricular
      fibrillation circulatory arrest and 5 min of external CPR, all animals received
      50 micrograms/kg of epinephrine and either nimodipine (10 micrograms/kg, followed
      by 1 microgram.kg-1.min-1 until termination of the experiment) or placebo. Organ
      blood flow was measured using radioactive-labeled microspheres. The rate of
      resuscitability in nimodipine-treated pigs (11 of 12) was significantly higher (P
      < 0.05) than in placebo-treated animals (7 of 14). In pigs receiving epinephrine
      and nimodipine, left ventricular blood flow after restoration of spontaneous
      circulation (ROSC) was approximately twice as high as in pigs receiving
      epinephrine and placebo (P < 0.01). In nimodipine-treated pigs, total cerebral
      blood flow 10 min after ROSC was significantly higher than baseline values (P <
      0.01) and in hypophysis, cerebellum, and medulla the blood flows were
      significantly higher than in placebo-treated pigs (P < 0.05). We conclude that,
      in our pig model, high doses of nimodipine given during CPR caused significant
      enhancements in left ventricular blood flow and significantly improved the rate
      of resuscitation.

PMID- 8267188
TI  - A comparison of epidural catheters with or without subcutaneous injection ports
      for treatment of cancer pain.
AB  - The aim of this study was to compare the incidence of technical complications of
      epidural catheters with subcutaneous injection ports to percutaneous epidural
      catheters without ports, fixed only by adhesive dressing. We reviewed 149
      patients who received 250 epidural catheters for treatment of cancer pain during
      a 3 1/2-yr period from January 1, 1989, to June 30, 1992. Of the 250 catheters,
      52 were provided with subcutaneous injection ports and 198 were percutaneous
      catheters. Of the 198 percutaneous catheters, 41 were tunneled for a short
      distance; the remainder entered the skin at the dorsal midline. In the
      percutaneous group 21% of the catheters became dislodged. In the injection port
      group, there were no catheter dislodgements. The overall incidence of infections
      was similar in both groups (13.6%). When we indexed the infection rate to
      catheter-days, the number of infections per 1000 catheter-days in the injection
      port group was half that of the percutaneous group (2.86 infections versus 5.97
      for percutaneous catheters). No injection port became infected during the first
      70 days of treatment, whereas in the percutaneous group infections occurred as
      early as the first week. Within the percutaneous group the complication rate in
      the tunneled epidural catheters was as high as in the nontunneled. We conclude
      that injection ports reduce the complication rate of epidural catheters,
      particularly catheter dislodgement and early infections.

PMID- 8267189
TI  - Spinal cord as a site of anesthetic action.

PMID- 8267190
TI  - Epidural clonidine treatment for refractory reflex sympathetic dystrophy.
AB  - BACKGROUND: Intraspinally administered alpha 2-adrenergic agonists may relieve
      pain in sympathetically maintained pain (SMP) syndromes, such as reflex
      sympathetically dystrophy (RSD), by spinal, peripheral, and central nervous
      system actions. This study examined analgesic efficacy and side effects of
      epidurally administered clonidine in patients with severe, refractory RSD.
      METHODS: Twenty-six patients with severe chronic pain consistent with RSD were
      studied in a randomized, blinded, placebo-controlled design. Cervical or lumbar
      epidural catheters were inserted for patients with upper or lower extremity RSD,
      respectively, and patients received, in random order on three consecutive days,
      epidural injection of clonidine, 300 or 700 micrograms, or placebo. Pain (by
      visual analog score (VAS) and McGill Pain Questionnaire), sedation, blood
      pressure, and heart rate were monitored at specified intervals for 6 h after
      injection. Patients who responded to clonidine, but not placebo, then entered a
      trial of open-label, continuous epidural infusion of clonidine (10-50
      micrograms/h). RESULTS: Clonidine, but not placebo, caused pain relief, sedation,
      and decreased blood pressure and heart rate after bolus epidural injection. The
      smaller clonidine dose (300 micrograms), produced pain relief and decreases in
      blood pressure and heart rate similar to those of the 700 micrograms dose, but
      with less sedation. Epidural clonidine was infused for a mean of 43 days in 19
      patients at a mean rate of 32 micrograms/h for sustained analgesia. CONCLUSIONS:
      Transdermal clonidine has been demonstrated to produce analgesia in the area
      surrounding its application site in patients with SMP. The current study
      indicates that extensive analgesia may be obtained by epidural administration.
      Sedation and hypotension may limit bolus epidural clonidine administration for
      RSD. The role for chronic epidural infusion of clonidine has not yet been
      established.

PMID- 8267191
TI  - Use of the electrospinogram for predicting harmful spinal cord ischemia during
      repair of thoracic or thoracoabdominal aortic aneurysms.
AB  - BACKGROUND: To reduce the incidence of misleading assessments, and to derive
      criteria for critical spinal cord ischemia during thoracic or thoracoabdominal
      aortic aneurysm repair, the authors epidurally stimulated and recorded
      somatosensory evoked potentials (ESEP) below and above, respectively, the spinal
      segment at risk (electrospinogram). METHODS: Epidural somatosensory evoked
      potentials were analyzed in 100 consecutive patients undergoing resection of
      aortic aneurysms using two bipolar catheters (stimulation at the L2 level and
      recording at the T3 level) for the following criteria: 1) the time until ESEP
      disappeared completely after cross clamping, 2) the duration of complete ESEP
      loss during and after cross clamping, and 3) the time until ESEP recovered after
      declamping. Postoperatively, neurologic deficits were evaluated by a neurologist
      who was unaware of the ESEP recordings. RESULTS: Three types of patients could be
      identified. First, thirty-one patients neither showed ESEP loss nor neurologic
      deficits. Second, ESEP loss occurring later than 15 min after cross clamping was
      associated with a neurologic deficit in 2 of 29 patients (6.9%). And, third, 12
      of 40 patients (30%) presented a neurologic deficit when ESEP loss occurred
      within 15 min after cross clamping. Further indicators of an impending risk were
      a total ESEP loss greater than 40 min (sensitivity 100%, specificity 68%,
      positive predictive value [PPV] 35%, and negative predictive value [NPV] 100%),
      and a recovery of ESEP later than 20 min after declamping (sensitivity 93%,
      specificity 86%, PPV 52%, and NPV 99%). CONCLUSIONS: Epidural somatosensory
      evoked potentials appeared to be a reasonable intraoperative predictor of
      postoperative neurologic outcome, and informs surgeons and anesthesiologists
      about the impending danger at an early state of the operation.

PMID- 8267192
TI  - Propofol depresses the hypoxic ventilatory response during conscious sedation and
      isohypercapnia.
AB  - BACKGROUND: Propofol infusion at subanesthetic doses provides reliable conscious
      sedation. However, the ventilatory effects of sedative doses of propofol have not
      been established. The current study was conducted to determine the effects of
      propofol sedation on the hypoxic ventilatory response. METHODS: Eight healthy,
      male volunteers received 1 mg.kg-1 propofol followed by a propofol infusion
      adjusted to maintain a constant, subanesthetic level of sedation. Hypoxic
      ventilatory response was measured using an isocapnic rebreathing technique: while
      keeping PETCO2 constant (approximately 6 mmHg above prestudy baseline), the
      authors continuously recorded minute ventilation and tidal volume, as oxygen
      saturation (SpO2) decreased from 98 to 70%. Hypoxic response determinations were
      performed before and during propofol infusion, as well as 30 and 60 min after
      termination of the propofol infusion. RESULTS: The slope of the hypoxic
      ventilatory response curve (VE vs. SpO2) decreased from 0.88 +/- 0.15 to 0.17 +/-
      0.03 l.min-1.%SpO2 -1 during propofol sedation (mean +/- SE). Thirty minutes
      after discontinuation of the propofol infusion, slope returned to its prepropofol
      value. In addition, minute ventilation at SpO2 = 90% decreased during propofol
      sedation, from 16.1 +/- 0.8 to 8.7 +/- 0.4 l.min-1, accompanied by a similar
      decrease in tidal volume at SpO2 = 90%, from 1,099 +/- 87 to 523 +/- 21 ml.
      Thirty minutes after discontinuation of the propofol infusion, these variables
      also returned to their prepropofol values. CONCLUSIONS: The authors concluded
      that propofol infusion for conscious sedation significantly decreases the slope
      and causes a downward shift of the hypoxic ventilatory response curve measured
      during isohypercapnia.

PMID- 8267193
TI  - The interactions of midazolam and flumazenil on human memory and cognition.
AB  - BACKGROUND: Previous research has been unable to show unequivocally whether
      flumazenil can reverse completely, partially, or not at all the memory effects of
      benzodiazepines. The effects of midazolam on implicit memory are also unknown.
      The behavioral effects of flumazenil by itself, and the acute reversal of
      benzodiazepine effects, are also controversial. The current study was designed to
      investigate these questions. METHODS: Using a prospective randomized, double
      blind crossover study design, memory was assessed using both direct (free recall
      and recognition) and indirect (word completion) measures. Other cognitive effects
      were assessed using the digit symbol substitution task. Sedation and other mood
      effects were assessed using subjective rating scales. Seventy-two healthy
      subjects were assigned to three equal groups according to the dose of midazolam
      received (0, 0.05, and 0.1 mg/kg). Each subject received varying doses of
      flumazenil (0, 1, and 3 mg) in three sessions, at least 1 week apart. After
      baseline administration of the tasks, midazolam was administered. The assessments
      were repeated 20 min later, followed by administration of flumazenil. The
      assessments were repeated 5 and 30 min after administration of flumazenil. After
      a 2-h recovery period, delayed memory tests were given. RESULTS: Both doses of
      midazolam decreased all scores in the memory and digit symbol substitution tests
      and mood ratings. Flumazenil reversed both the sedative and the memory effects of
      the benzodiazepine. The reversal was as complete with the 1-mg dose of flumazenil
      as with the 3-mg dose. Flumazenil by itself, and the acute reversal of midazolam
      effects, caused no significant behavioral reactions. CONCLUSIONS: Midazolam
      impairs explicit and implicit memory. Flumazenil reverses both the sedative and
      memory effects of the drug. Flumazenil, in the doses used, has no intrinsic
      actions.

PMID- 8267194
TI  - Naloxone, meperidine, and shivering.
AB  - BACKGROUND: Meperidine, which binds both mu and kappa opioid receptors, is
      reportedly more effective in treating shivering than are equianalgesic doses of
      morphine (a nearly pure mu-receptor agonist). Furthermore, butorphanol, a kappa
      receptor agonist/antagonist, treats shivering better than does fentanyl, which
      mostly binds mu receptors. These data indicate that much of meperidine's special
      antishivering activity may be mediated by its kappa activity. Accordingly, the
      authors tested the hypothesis that the antishivering activity of meperidine will
      be minimally impaired by low-dose naloxone (blocking most mu-receptors), but
      largely prevented by high-dose naloxone (blocking all mu and most kappa
      receptors). METHODS: Twelve volunteers each participated on 2 days. On both days,
      shivering was induced by central venous infusion of cold fluid. Twenty minutes
      later, six volunteers were given a placebo infusion of saline on one day, or an
      infusion of 0.5 microgram.kg-1.min-1 naloxone hydrochloride ("low-dose," designed
      to block mu receptors) on the other. The second group of six volunteers was given
      a saline bolus and infusion on one day, or a bolus of 11.5 micrograms/kg naloxone
      hydrochloride followed by an infusion of naloxone at 5 micrograms.kg-1.min-1
      ("high-dose," designed to block both mu and kappa receptors) on the other day.
      The infusions were continued for the duration of the study. The order of the
      treatment days (saline vs. naloxone) was randomly assigned, and the study was
      double blinded. Fifteen minutes after the test infusion was started, all 12
      volunteers were given an intravenous bolus of 1 mg/kg meperidine hydrochloride.
      Pupillary diameter and light reflex amplitude were used to quantify opioid
      receptor agonist activity; shivering intensity was evaluated using oxygen
      consumption. RESULTS: Administration of naloxone alone did not alter oxygen
      consumption, pupil size, or the pupillary light reflex. No pupillary constriction
      was detected in either group when naloxone and meperidine were combined; in
      contrast, meperidine alone decreased pupil size and amplitude of the light reflex
      30%. The meperidine bolus decreased oxygen consumption nearly to control values
      when the volunteers were given saline placebo. Combined administration of
      meperidine and low-dose naloxone also significantly reduced oxygen consumption,
      but the reduction and the duration of the reduction was less than during saline.
      When the volunteers were given high-dose naloxone, meperidine only slightly
      reduced oxygen consumption, and the values rapidly returned to premeperidine
      levels. CONCLUSIONS: These data indicate that the antishivering property of
      meperidine is not fully mediated by mu-receptors. Although meperidine has well
      known nonopioid actions, stimulation of kappa receptors seems a likely
      alternative explanation for much of the drug's antishivering action.

PMID- 8267195
TI  - Determinants of catecholamine and cortisol responses to lower extremity
      revascularization. The PIRAT Study Group.
AB  - BACKGROUND: Surgical trauma elicits diffuse changes in hormonal secretion and
      autonomic nervous system activity. Despite studies demonstrating modulation of
      the stress response by different anesthetic/analgesic regimens, little is known
      regarding the determinants of catecholamine and cortisol responses to surgery.
      METHODS: Plasma catecholamines and cortisol secretion data were obtained from 60
      patients undergoing lower extremity revascularization. Patients were randomized
      to receive either general anesthesia combined with patient-controlled intravenous
      morphine (GA) or epidural anesthesia combined with epidural fentanyl analgesia
      (RA). All aspects of intra- and postoperative clinical care were defined by
      written protocol. Plasma catecholamines were measured before induction,
      intraoperatively, and for the first 18 h postoperatively (by HPLC). Urine
      cortisol was measured intra- and postoperatively using RIA. Data were evaluated
      using univariate and multivariate analyses to evaluate demographic and
      perioperative variables as determinants of stress hormone secretion. RESULTS:
      Plasma catecholamines increased during skin closure in the GA group, and remained
      higher relative to the RA group in the postoperative period. Multivariate
      analysis indicated that age and anesthetic regimen predicted increases in
      catecholamines during skin closure (P < 0.005), although duration of surgery,
      blood loss, and body temperature were not correlated. Early postoperative
      norepinephrine concentrations were correlated with pain score and duration of
      surgery (P < 0.004), but not with anesthetic management, blood loss, or body
      temperature. All postoperative norepinephrine levels were highly correlated (r =
      0.7) with norepinephrine levels during skin closure. Cortisol excretion was
      higher postoperatively than intraoperatively. No patient or perioperative
      variable predicted cortisol excretion, and cortisol excretion was not correlated
      with catecholamine levels at any time. CONCLUSIONS: These data indicate that
      patient factors, such as age and inherent sympathetic responsivity, are important
      determinants of the catecholamine response to surgery. Modulation of the
      norepinephrine response by regional anesthesia/analgesia appears to be related,
      in part, to superior analgesia. The lack of correlation between catecholamine and
      cortisol secretion indicates that the stress response may consist of discrete
      systems responding to different stimuli.

PMID- 8267196
TI  - Anesthetic and obstetric outcome in morbidly obese parturients.
AB  - BACKGROUND: Large studies reporting anesthetic outcome for morbidly obese
      parturients are lacking. This study compares the anesthetic and obstetric outcome
      in morbidly obese parturients and matched control parturients. METHODS:
      Anesthesia records were prospectively collected for all patients delivering
      between September 1978 and November 1989 whose weight exceeded 136.4 kg (300
      pounds) at the time of delivery. A retrospective control patient group was
      collected by matching the first patient weighing less than 136.4 kg, delivered in
      the same month by the same obstertrician, to the corresponding morbidly obese
      parturient. Anesthetic and obstetric outcome variables were extracted from
      medical records and analyzed. RESULTS: Sixty-two percent of 117 morbidly obese
      women underwent cesarean section, while only 24% of control patients delivered
      abdominally (P < 0.05). Forty-eight percent of all laboring morbidly obese
      parturients required emergency cesarean section, compared with 9% of control
      laboring parturients (P < 0.05). Epidural anesthesia was used successfully for
      labor and cesarean delivery in 74 of 79 morbidly obese women and 66 of 67 control
      patients. When compared with control patients, initial epidural anesthesia
      failure was significantly more likely in morbidly obese women, requiring epidural
      catheter replacement. Difficult tracheal intubation occurred in 6 of 17 morbidly
      obese women, compared with 0 of 8 control women (P = 0.06). Morbidly obese women
      had increased incidences of antepartum medical disease, prolonged cesarean
      section operation times, serious postoperative complications, and increased
      hospital stays. CONCLUSIONS: The high incidences of antepartum medical disease
      and emergency cesarean section complicate anesthetic care in the morbidly obese
      parturients. Epidural anesthesia is feasible; however, the high initial failure
      rate necessitates early catheter placement, critical block assessment and
      catheter replacement when indicated, and provision for alternative airway
      management.

PMID- 8267197
TI  - Does the choice of local anesthetic affect the catecholamine response to stress
      during epidural anesthesia?
AB  - BACKGROUND: Previous work has established that 2-chloroprocaine epidural
      anesthesia has no effect on circulating plasma epinephrine concentrations in
      young, healthy, resting volunteers, and results in a decrease in norepinephrine
      concentration only when a level of analgesia to pinprick of C-8 is reached. The
      current study was performed to evaluate the possibility that this finding is
      unique to 2-chloroprocaine. METHODS: Nine healthy volunteers were studied on
      three occasions at least 48 h apart; each received three local anesthetics (0.75%
      bupivacaine, 2% lidocaine, and 3% 2-chloroprocaine, all without epinephrine).
      After placement of lumbar epidural and central venous catheters, blood samples
      were drawn from the central venous catheter at the following stages: (1) 20 min
      after catheter placement (baseline), (2) during the first cold pressor test (CPT;
      hand held in an ice water bath for 90 s), (3) 20 min after reaching epidural
      analgesia to T-1 level of analgesia, and (4) during a second CPT (epidural
      analgesia to T-1). Monitoring consisted of noninvasive cardiac output
      (impedance), noninvasive blood pressure, and EKG. RESULTS: Extensive epidural
      block (stage 3) altered measured variables only minimally with respect to resting
      baseline state. During stage 2 (first CPT), mean arterial pressure (MAP), heart
      rate (HR), cardiac index (CI), epinephrine, and norepinephrine increased. During
      stage 4 (second CPT), increases in HR and CI were not attenuated by any of the
      three local anesthetics. Increases in MAP were attenuated by epidural anesthesia
      with all three local anesthetics. Bupivacaine and 2-chloroprocaine epidural
      anesthesia significantly attenuated increases in plasma catecholamines, but
      lidocaine epidural anesthesia did not. CONCLUSIONS: Epidural anesthesia with all
      three local anesthetic agents tested resulted in an incomplete sympathectomy in
      the resting state in healthy young men, judged by plasma catecholamine
      concentrations and cardiovascular variables minimally changed from resting
      baseline. Lidocaine epidural anesthesia did not attenuate the catecholamine
      response to CPT, indicating decreased blockade of sympathetic efferent neural
      traffic compared with bupivacaine and chloroprocaine epidural anesthesia.

PMID- 8267198
TI  - Hypnotic and anesthetic interactions between ketamine and midazolam in female
      patients.
AB  - BACKGROUND: Midazolam, if used with ketamine for induction and maintenance of
      anesthesia, may attenuate hyperdynamic circulatory effects and prevent
      undesirable emergenic reactions. The nature of the interaction between midazolam
      and ketamine used for anesthesia induction was studied in female patients.
      METHODS: Quantal dose-response curves were determined in 170 female patients for
      the drugs, individually and in combination. Two endpoints were assessed, loss of
      response to verbal command (hypnosis) and loss of response to a 5-s
      transcutaneous tetanus (anesthesia). At the hypnotic endpoint, interactions were
      analyzed by fitting the data to a mathematical model in which the response was
      analyzed in terms of the doses of the two drugs, and an additional term was
      included to describe nonadditive interactions. At the anesthetic endpoint, the
      decrease in ED50 of ketamine in the presence of midazolam was assessed because
      dose-related effects could not be demonstrated for midazolam alone. RESULTS: At
      the hypnotic endpoint, the ED50s were: 0.15 mg/kg midazolam (95% CIs 0.11-0.38
      mg/kg), 0.37 mg/kg ketamine (95% CIs 0.08-0.44 mg/kg), and the combination of
      0.086 mg/kg midazolam and 0.27 mg/kg ketamine (95% CIs 0.07/0.22-0.10/0.31
      mg/kg), respectively. The hypnotic effects were found to be additive, and there
      was no evidence of an interaction. At the anesthetic endpoint, the ED50 of
      ketamine alone was 0.57 mg/kg (95% CIs 0.47-0.69) and the ED50 for ketamine in
      the presence of midazolam was also 0.57 mg/kg (95% CIs 0.48-0.79); 0.18 mg/kg
      midazolam was given at this point. Midazolam had no influence on the anesthetic
      dose of ketamine. CONCLUSIONS: When using the combination, doses employed should
      be adjusted according to the depth of central nervous system depression that is
      required.

PMID- 8267199
TI  - Ventilation, thermal noise, and errors in cardiac output measurements after
      cardiopulmonary bypass.
AB  - BACKGROUND: The authors observed transient increases in the amplitude of
      respiratory variations in pulmonary artery blood temperature in many patients
      after cardiopulmonary bypass (CPB). This increased "thermal noise" may
      significantly influence measurements of thermodilution cardiac outputs (TDCO)
      performed during this time. METHODS: The authors recorded the peak-to-peak
      amplitude of respiratory variations in pulmonary artery blood temperature in 15
      patients during the first 35 min after CPB. Possible relationships between the
      amplitude of these variations and the magnitude of temperature differences
      between commonly monitored body temperature sites (nasopharyngeal, rectal,
      bladder, and pulmonary artery) were also examined. In ten additional patients,
      the authors investigated the influence of these increased respiratory variations
      on TDCO measurements by correlating the maximum variation in three successive
      TDCO measurements with the peak-to-peak amplitude of the respiratory variations
      in pulmonary artery blood temperature. Potential error in TDCO measurements
      caused by these increased respiratory variations in pulmonary artery blood
      temperature were also examined using model calculations of the effects of
      respiratory variations in pulmonary artery blood temperature on measured TDCO
      thermal areas. RESULTS: In the first 15 patients, the mean amplitude of
      respiratory variations in pulmonary artery blood temperature after CPB (mean +/-
      SEM) were: (1) within 5 min after CPB, 0.037 +/- 0.004 degrees C; (2) 10 min
      after #1, 0.025 +/- 0.003 degrees C; (3) 20 min after #1, 0.019 +/- 0.003 degrees
      C; and (4) 30 min after #1, 0.012 +/- 0.002 degrees C. There were no significant
      correlations between the magnitude of the respiratory variation in pulmonary
      artery blood temperature and the observed temperature differences between body
      sites. Four patients had pulmonary artery blood temperature variations in excess
      of the maximum amplitude previously reported in man (0.05 degrees C). In the next
      ten patients, the maximum variation between three successive TDCO measurements
      taken at specified times in the respiratory cycle (end inspiration, end
      exhalation, and 3 s after end exhalation) was significantly correlated with the
      amplitude of respiratory variations in pulmonary artery blood temperature (r =
      0.83, P < 0.001). Four patients with increased respiratory variations in
      pulmonary artery blood temperature had variations in TDCO measurements exceeding
      2 l/min. Subsequent model calculations demonstrated that the magnitude of
      potential error in TDCO measurements is dependent on both the amplitude of the
      respiratory variations in pulmonary artery blood temperature and the baseline
      cardiac output. On the basis of these thermal area calculations, potential errors
      of 15-50% could be caused by respiratory variations in pulmonary artery blood
      temperature > 0.05 degrees C. CONCLUSIONS: The authors concluded that respiratory
      variations in pulmonary artery blood temperature are transiently increased in
      many patients after CPB, and that this increased "thermal noise" may cause
      significant errors in TDCO measurements.

PMID- 8267200
TI  - Exaggerated anesthetic requirements in the preferentially anesthetized brain.
AB  - BACKGROUND: The brain is assumed to be the site of anesthetic action, but
      anesthetics have effects elsewhere, such as the spinal cord. A preferentially
      anesthetized goat brain model was used to determine the importance of anesthetic
      action in the brain. METHODS: Six goats were anesthetized with isoflurane; after
      tracheal intubation and insertion of a femoral arterial catheter, bilateral neck
      dissections were performed to isolate the external carotid arteries and external
      jugular veins. The occipital arteries were ligated to prevent vertebral blood
      from entering the carotid system. (Goats do not have direct, significant
      vertebral artery contributions to the brain, and they lack internal jugular
      veins.) Control isoflurane minimum alveolar concentration (MAC) was determined
      using a dew-claw clamp as the painful stimulus. Following this, cranial venous
      blood was drained into a bubble oxygenator in which an isoflurane vaporizer was
      placed in line with the gas flow. Oxygenator arterial isoflurane concentration
      was estimated from the isoflurane partial pressure in the oxygenator exhaust.
      Isoflurane administration via the lungs was discontinued and the isoflurane
      partial pressure in the blood delivered via the carotid artery was increased by
      an amount required to bracket the partial pressures permitting and preventing
      movement in response to dew-claw stimulation. The native circulation was
      reestablished and MAC determined again. RESULTS: Cerebral isoflurane requirements
      were 1.2 +/- 0.3% (mean +/- SD) before bypass, increased to 2.9 +/- 0.7% during
      bypass when the brain was preferentially anesthetized, and decreased to 1.3 +/-
      0.1% after bypass. CONCLUSIONS: The results support the importance of subcortical
      structures, such as the spinal cord, in the generation of purposeful movement in
      response to a painful stimulus under general anesthesia.

PMID- 8267202
TI  - Halothane and temperature interact to increase succinylcholine-induced jaw
      contracture in the rat.
AB  - BACKGROUND: The agonist actions of succinylcholine (SCh) have recently come under
      study because of their involvement in the clinical problem of masseter muscle
      rigidity, and their possible involvement in malignant hyperthermia. The authors
      investigated factors affecting SCh-induced contractures in an animal preparation.
      METHODS: Rats were anesthetized with either halothane (1-2%) or pentobarbital.
      Resting and twitch isometric tension were measured from the jaw muscles.
      Succinylcholine (500 or 750 micrograms/kg) was administered intravenously,
      producing increases in resting tension (i.e., contractures). Jaw muscle
      temperature was controlled by radiant heat. RESULTS: Succinylcholine increased
      jaw muscle tension for several seconds. These contractures exhibited
      tachyphylaxis, and were antagonized by vecuronium (0.8-1.5 mg/kg), indicating
      mediation by acetylcholine receptors (AChR). In the presence of 2% halothane,
      contractures were tenfold greater at a rectal temperature of 41 degrees C than at
      37 degrees C. In contrast, under 50 mg/kg intraperitoneal pentobarbital
      anesthesia, contractures were not affected by rectal temperature. Neither the
      half-decay time of contracture nor twitch tension (0.2 Hz, preceding SCh) were
      increased in the presence of halothane at 41 degrees C. In a set of experiments
      in which rectal temperature was maintained at 37 degrees C but jaw temperature
      was varied between 36-41 degrees C, there was a significant regression of SCh
      induced jaw contracture on temperature in the presence of halothane. In contrast,
      there was no significant relationship between jaw temperature and contracture in
      the presence of pentobarbital. CONCLUSIONS: These results in the rat demonstrate
      a temperature-dependent interaction between halothane and SCh that has not
      previously been described.

PMID- 8267201
TI  - Effects of epidural and systemic lidocaine on sympathetic activity and mesenteric
      circulation in rabbits.
AB  - BACKGROUND: The mechanisms producing hemodynamic changes during epidural
      anesthesia are incompletely understood. This study examines the sympathetic block
      and splanchnic venodilatation that result from extensive thoracolumbar epidural
      anesthesia in rabbits using direct measurements of sympathetic efferent nerve
      activity (SENA) and mesenteric vein diameter (VD). METHODS: Epidural catheters
      were inserted in rabbits anesthetized with alpha-chloralose, paralyzed with
      vecuronium, and receiving mechanical ventilation. Arterial pressure was monitored
      with a femoral cannula, heart rate was determined from the pressure signal, SENA
      was measured from a postganglionic splanchnic nerve, and VD was measured from
      segments of ileum externalized in situ. Epidural anesthesia was induced with 0.4
      ml/kg lidocaine, using concentrations of either 0.5, 1, or 1.5%. Control animals
      received intramuscular lidocaine in a dose of either 6 or 15 mg/kg. After
      recovery from epidural anesthesia, complete sympathetic blockade was induced by
      systemic administration of the ganglionic blocker hexamethonium (HX). Individual
      groups included from five to eight animals. RESULTS: A mild decrease in arterial
      pressure and SENA followed the larger dose of intramuscular lidocaine, but no
      changes occurred in VD in the control animals exposed to systemic lidocaine at
      levels comparable to that in the epidural groups (0.96-3.58 micrograms/ml).
      Epidural injectate extended from T2 to L5. All concentrations of epidural
      lidocaine produced comparable degrees of hypotension (-53.5 to -61.4%), decreased
      SENA (-82.6 to -95.5%), and increased VD (7.5 to 10.2%). The duration of the
      changes was greater with more concentrated lidocaine. Hexamethonium produced
      changes in arterial pressure and VD comparable to those evoked by epidural
      anesthesia. CONCLUSIONS: Epidural anesthesia increases splanchnic venous
      capacitance by markedly decreasing splanchnic sympathetic nerve activity.

PMID- 8267203
TI  - Electromechanical association in regionally stunned swine myocardium.
AB  - BACKGROUND: Postischemic myocardial dysfunction ("stunned" myocardium) is a
      common problem after cardiac surgery and cardiac transplantation. A "low-voltage"
      QRS complex in the electrocardiogram is also often seen in patients with severe
      cardiac dysfunction. The authors investigated the relationship between mechanical
      function and electrographic characteristics in postischemic swine myocardium, and
      determined whether inotropic stimulation with dobutamine alters the electrogram
      while improving mechanical function. METHODS: Regional wall thickening and
      regional electrogram from electrodes in the endo- and epicardium were measured in
      12 pigs during intravenous infusion of several doses of dobutamine (1-25
      micrograms.kg-1.min-1) before and after 10 or 15 min of ischemia followed by 1 h
      of reperfusion. RESULTS: Wall thickening was abolished after ischemia and
      reperfusion, and QRS amplitude decreased 25% in the endocardium and 29% in the
      epicardium. Dobutamine infusion restored both wall thickening and myocardial QRS
      amplitude to baseline values. The correlation between myocardial QRS amplitude
      and systolic wall thickening was significant in each animal (r = 0.88 +/- 0.02
      (mean +/- 1 SEM, n = 12); median r = 0.89; range 0.74-0.95, P < 0.01, for all
      relations). CONCLUSIONS: This study showed a close association between local
      electrical and mechanical events in postischemic swine myocardium.

PMID- 8267204
TI  - Methylprednisolone increases sensitivity to beta-adrenergic agonists within 48
      hours in Basenji greyhounds.
AB  - BACKGROUND: Corticosteroids used in combination with bronchodilators are
      significantly more effective than placebo combined with bronchodilators in the
      acute treatment of bronchospasm. Because the time course for this effect is not
      known, and is of importance in the preoperative preparation of patients with
      reactive airway disease, the authors investigated the time course by which
      methylprednisolone increased sensitivity to the beta-adrenergic agonist,
      albuterol, in a dog model with airway hyperresponsiveness. METHODS: Airway
      responsiveness to methacholine alone and in the presence of albuterol was
      determined before treatment with methylprednisolone in nine Basenji greyhounds.
      Each dog was then treated with methylprednisolone for 1 week. Airway
      responsiveness to methacholine in combination with albuterol was determined after
      24 h, 48 h, and 1 week of methylprednisolone treatment. RESULTS: Albuterol alone
      did not alter airway responsiveness to methacholine in Basenji greyhounds before
      methylprednisolone treatment and after 24 h of methylprednisolone treatment.
      Methylprednisolone, however, significantly decreased pulmonary responses to
      methacholine in albuterol-pretreated dogs at 48 h. CONCLUSIONS: The authors
      concluded that methylprednisolone increased sensitivity to the beta-adrenergic
      agonist, albuterol, within 48 h.

PMID- 8267205
TI  - Mechanism of the direct, negative inotropic effect of etomidate in isolated
      ferret ventricular myocardium.
AB  - BACKGROUND: Etomidate exerts a mild, positive inotropic effect in rat ventricular
      myocardium, yet has a negative inotropic effect in isolated rabbit ventricular
      myocardium. The aim of this study was to investigate the mechanisms of
      etomidate's inotropic effect and its underlying mechanism in isolated ferret
      ventricular myocardium (which shows similar physiologic characteristics as human
      ventricular myocardium) and in frog ventricular myocardium, in which Ca++ ions
      for myofibrillar activation are derived almost entirely from transsarcolemmal
      influx. METHODS: The authors analyzed the effects of etomidate after beta
      adrenoceptor blockade on variables of contractility and relaxation, and on the
      free intracellular Ca++ transient detected with the Ca+(+)-regulated photoprotein
      aequorin. Etomidate's effects were also evaluated in ferret right ventricular
      papillary muscles in which the sarcoplasmic reticulum (SR) function was impaired
      by ryanodine, and in frog ventricular strips with little or no SR function.
      RESULTS: At concentrations > or = 3 micrograms/ml, which by far exceed the
      clinically useful concentration range, etomidate decreased contractility and the
      amplitude of the intracellular Ca++ transient. At equal peak force, control peak
      aequorin luminescence in [Ca++]o = 2.25 mM and peak aequorin luminescence in
      etomidate 10 micrograms/ml and [Ca++]o > 2.25 mM did not differ, which indicates
      that etomidate does not alter myofibrillar Ca++ sensitivity. After inactivation
      of sarcoplasmic reticulum Ca++ release with ryanodine 10(-6) M, a condition in
      which myofibrillar activation depends almost exclusively on transsarcolemmal Ca++
      influx, etomidate caused a decrease in contractility and in the amplitude of the
      intracellular Ca++ transient, and etomidate's relative negative inotropic effect
      was not different from that in control muscles not exposed to ryanodine.
      Etomidate 10 micrograms/ml decreased contractility in frog ventricular
      myocardium. CONCLUSIONS: These findings indicate that the direct negative
      inotropic effect of etomidate results from a decrease in intracellular Ca++
      availability with no changes in myofibrillar Ca++ sensitivity. At least part of
      etomidate's action is caused by inhibition of transsarcolemmal Ca++ influx. Yet,
      these effects become apparent only at concentrations that are at least one order
      of magnitude larger than those encountered in clinical practice.

PMID- 8267206
TI  - Halothane-induced cytotoxicity to rat centrilobular hepatocytes in primary
      culture is not increased under low oxygen concentration.
AB  - BACKGROUND: Halothane can be metabolized by both oxidative and reductive pathways
      in the liver. This anesthetic can induce direct liver injury preferentially
      localized in centrilobular areas, probably in relation with lower oxygen tension.
      The reductive pathway has been related to liver damage; however, a correlation
      between lower oxygen concentration in centrilobular areas, the extent of
      reductive metabolism of halothane, and the degree of liver injury has not yet
      been demonstrated. This study was designed to better evaluate the toxicity of the
      reduced metabolites by using centrilobular and periportal rat hepatocyte
      subpopulations. METHODS: Adult rat hepatocytes, either as whole cell preparations
      or after separation in centrilobular and periportal cell subpopulations, were
      placed in primary culture and exposed to either 2% or 4% halothane under various
      oxygen concentrations. The enriched centrilobular hepatocyte subpopulations
      isolated by the digitonin-collagenase method were characterized by
      immunolocalization of glutamine synthetase. Three oxygen concentrations were
      tested: 5%, 20%, and 95%, and the main parameters measured were cell viability
      and fluoride ion formation. RESULTS: Viability of centrilobular hepatocytes was
      similar under 5% and 20% O2, but the unpurified hepatocyte population was more
      susceptible to 5% O2 (P < 0.01). Significantly higher cytochrome P-450 content
      was found in whole hepatocyte populations under 5% versus 20% oxygen, indicating
      that centrilobular hepatocytes that contained higher cytochrome P-450
      monooxygenase activities were less sensitive to low oxygen concentrations.
      Halothane toxicity to centrilobular hepatocytes was enhanced under 95% versus 20%
      O2 (P < 0.05). By contrast, no significant difference was observed when the cells
      were maintained under 5% O2, although fluoride ions, indicative of reductive
      metabolism of halothane, were found in much higher amounts in the culture medium.
      Moreover, under 20% O2, halothane toxicity was significantly greater in
      centrilobular versus unpurified hepatocytes (P < 0.05). CONCLUSIONS: Isolated
      centrilobular hepatocytes appear to be more sensitive to halothane than their
      periportal counterparts in vitro. However, the authors' results support the
      conclusion that increased reductive metabolism of halothane induced by decreasing
      oxygen concentration is not a critical parameter for the occurrence of liver
      damage in these cells.

PMID- 8267207
TI  - Anesthetics and automaticity of dominant and latent pacemakers in chronically
      instrumented dogs. I. Methodology, conscious state, and halothane anesthesia:
      comparison with and without muscarinic blockade during exposure to epinephrine.
AB  - BACKGROUND: Supraventricular dysrhythmias are common during anesthesia, but have
      been incompletely investigated. Mechanisms may involve altered automaticity of
      subsidiary pacemakers and participation of vagal reflexes. The following
      hypotheses were tested: (1) shifts from the sinoatrial (SA) node to subsidiary
      pacemakers require intact vagal reflexes and (2) halothane sensitizes the heart
      to epinephrine-induced atrial pacemaker shifts. METHODS: Epicardial electrodes
      were implanted in eight dogs on both atrial appendages, the right ventricle,
      along the sulcus terminalis, and at the His bundle. Weekly testing awake
      (control), awake with atropine methylnitrate, with 1 and 2 micrograms
      epinephrine.kg-1.min-1 (3 min-infusions), and under 1.25 and 2 MAC halothane was
      performed. Electrograms were analyzed for the site of earliest activation (SEA),
      which was scored 1-6 depending on the distance from the SA node, and expressed as
      the SEA value. RESULTS: In conscious dogs (control) and at 1.25 MAC halothane,
      epinephrine increased the SEA values (shifted activation from SA node) and blood
      pressure, and decreased heart rate; however, with atropine, SEA values were
      unaffected by epinephrine, although blood pressure and heart rate were elevated.
      At 2 MAC, atropine did not affect the epinephrine-induced increase in SEA values.
      Halothane increased SEA values when combined with 1 micrograms epinephrine.kg
      1.min-1. CONCLUSIONS: Pacemaker shifts account for atrial dysrhythmias in the
      conscious state and during 1.25 MAC halothane with epinephrine, and require vagal
      participation. Halothane sensitizes the heart to epinephrine-induced atrial
      dysrhythmias. Atropine and halothane facilitate His bundle beats during exposure
      to epinephrine.

PMID- 8267208
TI  - Anesthetics and automaticity of dominant and latent pacemakers in chronically
      instrumented dogs. II. Effects of enflurane and isoflurane during exposure to
      epinephrine with and without muscarinic blockade.
AB  - BACKGROUND: Atrial dysrhythmias precede ventricular dysrhythmias during
      epinephrine-anesthetic sensitization, and may be caused by an altered
      relationship between automaticity of primary and subsidiary pacemakers. The
      following hypotheses were tested: (1) epinephrine-induced pacemaker shifts with
      enflurane or isoflurane require intact vagal reflexes and (2) these anesthetics
      sensitize the atrial myocardium to epinephrine-induced dysrhythmias. METHODS:
      Eight dogs were instrumented for chronic electrophysiologic investigation,
      including electrodes at the SA node, atrial appendages, right ventricle, and His
      bundle, and along the sulcus terminalis. After conscious-state testing, dogs were
      anesthetized with isoflurane or enflurane and exposed to epinephrine, with or
      without atropine methylnitrate. Eight-channel ECG recordings were analyzed before
      and during epinephrine infusions. Atrial pacemakers were assigned values 1-6 with
      increasing distance from the SA node, normalized and expressed as the site of
      earliest activation value (SEA). RESULTS: Epinephrine increased SEA values during
      enflurane or isoflurane anesthesia. Atropine enhanced this increase during
      enflurane anesthesia, but abolished the increase during isoflurane anesthesia.
      Enflurane increased SEA values only when combined with atropine. Isoflurane did
      not increase SEA values under any test conditions. CONCLUSIONS: With enflurane,
      epinephrine-induced atrial pacemaker shifts in chronically instrumented dogs are
      caused by direct depression of SA node automaticity or a relative increase of
      automaticity in subsidiary atrial pacemakers. With isoflurane, pacemaker shifts
      are caused by reflex-induced vagal suppression of SA node automaticity and escape
      of latent pacemakers. Enflurane sensitizes the atrial myocardium to dysrhythmias
      when combined with muscarinic blockade; isoflurane does not sensitize the atrium.

PMID- 8267209
TI  - Effects of inhalational anesthetics on biochemical events in growing neuronal
      tips.
AB  - BACKGROUND: The influence of general anesthetics on developing organs has been a
      source of concern for many years. The central nervous system, which is developing
      rapidly at the time of birth, is of special interest in this regard. In this
      study, the biochemical characteristics of developing neural tips (growth cones)
      were examined after exposure to anesthetics to elucidate the molecular mechanism
      by which long-lasting alterations in the nervous system, including
      neuroteratogenicity, as previously described, were evoked. METHODS: Neonatal rats
      were exposed to an atmosphere containing inhalational anesthetics (1% halothane
      or 75% nitrous oxide) or a control atmosphere (25% O2 and 75% N2) for 6 h at
      postnatal day 1. After this exposure, growth cone particles were isolated from
      the forebrain using a recently devised cell fractionation method at postnatal
      days 2, 3, 4, and 5. Protein composition, phosphoprotein patterns, and protein
      kinase C (PKC) activities of the isolated growth cones were compared between each
      group exposed to anesthetics and the control group. The dose-response
      relationship of the action of anesthetics on PKC activity was also examined (at
      0.5 and 0.75% halothane and 25 and 50% N2O). RESULTS: The increase in body weight
      and brain wet weight were not significantly affected by exposure to either
      anesthetic. No apparent influence on protein composition was observed by
      sodiumdodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). However,
      calcium-dependent protein phosphorylation of the 46 kDa protein and of the 80 kDa
      protein, which is reported to be mediated by PKC, were significantly reduced
      after exposure to the anesthetics. A direct assay of PKC activity in growth cone
      particles indicated that PKC activity in the growth cone was 70.6 +/- 9.6% of the
      control value at 24 h after exposure to 1% halothane, and 63.2 +/- 4.9% after
      exposure to 75% nitrous oxide. Exposure to 0.75% halothane or 50% nitrous oxide
      had a similar, but lesser, effect on this parameter. In contrast, exposure to
      0.5% halothane or 25% nitrous oxide evoked no apparent effect. Thus the PKC
      activity in growth cone particles, which is thought to play an important role in
      signal transduction in the developing brain, was shown to be affected by exposure
      to inhalational anesthetics over a range of concentrations. CONCLUSIONS:
      Considering the crucial role of growth cones in the establishment of the neuronal
      network, the interruption of signal transduction in the growth cone at a time
      that is critical in directing the neurite extension may evoke a long-lasting
      alteration in the neural network. Therefore, the effect of inhalational
      anesthetics on the growth cone enzyme observed in this study may have a major
      role in the mechanism that induces morphologic or behavioral neuroabnormalities
      in later life.

PMID- 8267210
TI  - Effect of sevoflurane on hypoxic pulmonary vasoconstriction in the perfused
      rabbit lung.
AB  - BACKGROUND: In vitro studies have shown that isoflurane, enflurane, and halothane
      inhibit the hypoxic pulmonary vasoconstriction (HPV) with essentially the same
      potency. The aim of this study is to compare the effects of sevoflurane and
      isoflurane on HPV in constant-flow perfused rabbit lungs. METHODS: Constant-flow
      perfused lungs from Japanese white rabbits were tested. The lungs were divided
      into three groups: isoflurane alone (n = 6), sevoflurane alone (n = 6), and
      sevoflurane with ibuprofen pretreatment (n = 6). Baseline HPV responses were
      measured as the pulmonary arterial pressure increased after changing inspired
      oxygen concentration from 95% for 15 min to 3% (with 5% CO2) for 5 min without
      anesthetic administration. Next, three different concentrations of anesthetics
      were added to the inspired gas for 15 min in random order. The HPV response in
      the presence of anesthetic was expressed as a percentage of the pressor response
      in the absence of anesthetics, and dose-response relationships were calculated
      using the nonlinear least-squares method. RESULTS: Isoflurane and sevoflurane
      both depressed the HPV response in a dose-related manner. The half-inhibition
      values (ED50) of HPV with isoflurane and sevoflurane were 0.85 +/- 0.22 MAC and
      1.00 +/- 0.12 MAC (mean +/- SD), respectively, and were not statistically
      different. Ibuprofen pretreatment did not alter ED50 and slope of dose-response
      curve, although the absolute value of pressor response in the sevoflurane group
      with ibuprofen pretreatment was greater than that in the sevoflurane alone group
      at every concentration of sevoflurane. CONCLUSIONS: Sevoflurane inhibits the HPV
      response in a dose-related manner, and its potency is similar to that of
      isoflurane in vitro. Cyclooxygenase products do not mediate the inhibition of HPV
      by sevoflurane.

PMID- 8267211
TI  - Role of the endocardial endothelium in the regulation of myocardial function.
      Physiologic and pathophysiologic implications.

PMID- 8267212
TI  - Integration of factors controlling vascular tone. Overview.

PMID- 8267213
TI  - Overall systems analysis of the carotid sinus baroreceptor reflex control of the
      circulation.

PMID- 8267214
TI  - Transfusion-associated graft-versus-host disease caused by leukocyte-filtered
      stored blood.

PMID- 8267215
TI  - Diffuse oral facial cavernous hemangioma causing severe airway obstruction after
      intramuscular ketamine.

PMID- 8267216
TI  - Aneurysmal compression of the trachea and right mainstem bronchus complicating
      thoracoabdominal aneurysm repair.

PMID- 8267217
TI  - Determination of intravascular migration of an epidural catheter using the air
      technique.

PMID- 8267218
TI  - Cardiopulmonary bypass in hereditary angioedema.

PMID- 8267219
TI  - The Lazarus phenomenon re-revisited.

PMID- 8267220
TI  - The proper study of anesthetized humans.

PMID- 8267221
TI  - The proper study of anesthetized humans.

PMID- 8267222
TI  - Anesthetic requirements decrease after cardiopulmonary bypass.

PMID- 8267223
TI  - Change in stroke volume by iced temperature injectate for thermodilution cardiac
      output determination.

PMID- 8267224
TI  - More on inspiratory stridor.

PMID- 8267225
TI  - The first anesthetic mixture: a correction.

PMID- 8267226
TI  - A new, simple method of measuring physiologic deadspace (Vdphys) and Vdphys/Vt
      ratio in patients whose lungs are mechanically ventilated.

PMID- 8267227
TI  - Disposable circuit disconnects.

PMID- 8267228
TI  - The beveled tracheal tube orifice abutted on the tracheal wall in a patient with
      Forestier's disease.

PMID- 8267229
TI  - Selective bronchial intubation with the univent system in patients with a
      tracheostomy.

PMID- 8267230
TI  - Hypotension after indigo carmine.

PMID- 8267231
TI  - Concrete thoughts about abstracts.

PMID- 8267232
TI  - Bacterial contaminants of collected and frozen human milk used in an intensive
      care nursery.
AB  - BACKGROUND: Use of human milk for preterm and high-risk neonates conveys many
      potential benefits but also poses practical difficulties. This prospective study
      examined the prevalence and degree of bacterial contamination of human milk used
      in the intensive care nursery. METHODS: One hundred eight milk samples collected
      from 40 mothers were tested for contamination. Samples from mothers whose milk
      showed a high degree of contamination were retested after counseling on
      collection methods. RESULTS: Only 12.5% of the samples showed no bacterial
      growth. Of the contaminated samples, 38% contained > 30,000 colony-forming
      units/ml. The most common contaminants were Staphylococcus epidermidis (82%) and
      Acinetobacter (9%), but other contaminants were also encountered. CONCLUSIONS:
      There were not statistically identifiable common characteristics of mothers whose
      milk showed abundant bacterial contamination. Only 30% of these mothers showed
      improvement in the degree of contamination after counseling regarding techniques
      of milk collection.

PMID- 8267233
TI  - Aerobes isolated in fecal microflora of infants in the intensive care nursery:
      relationship to human milk use and systemic sepsis.
AB  - BACKGROUND: Staphylococcus epidermidis is a leading cause of nosocomial sepsis in
      the intensive care nursery. The relationship between rates of gastrointestinal
      colonization and the incidence of systemic sepsis with S. epidermidis in
      hospitalized neonates is under investigation. METHODS: In this study, we enrolled
      46 infants consecutively admitted to the intensive care nursery (mean +/-
      standard deviation, birth weight 1300 +/- 337 gm, gestational age 29.4 +/- 2.2
      weeks). At the time of enrollment, infants had been fed enterally for at least 1
      week (28 were fed formula and 18 received their own mothers' frozen milk). Stool
      samples were collected when infants were 2 to 3 weeks of age (16.3 +/- 7.4 days).
      RESULTS: Aerobic stool flora were present in 65% of all patients. Human milk use
      was associated with a significant increase in the presence of aerobic stool flora
      (78% vs 46%, p = 0.035), as well as more frequent isolation of S. epidermidis.
      The incidence of S. epidermidis sepsis was 33% in those infants whose stool
      specimens grew S. epidermidis and 3.5% in those whose stool specimens did not (p
      < 0.01). CONCLUSIONS: These findings suggest the gastrointestinal tract as a
      possible site of entry for S. epidermidis in the hospitalized preterm infant. In
      addition, frozen human milk may be a vehicle for gastrointestinal S. epidermidis
      colonization.

PMID- 8267234
TI  - Immunologic benefits of breast milk in relation to human milk banking.
AB  - A review of the immunologic benefits of human milk is presented, with emphasis on
      the antiviral properties of human milk. These properties are so important to
      infant health that the World Health Organization has restated its recommendation.
      "In all populations, irrespective of HIV infection rates, breast-feeding should
      continue to be protected, promoted, and supported." Infection control procedures
      are described for human milk banking, which should be supported as an
      immunologically beneficial feeding alternative for infants.

PMID- 8267235
TI  - Blood contact and exposures among operating room personnel: a multicenter study.
AB  - Blood exposures are increasingly recognized as a risk for health care workers in
      the operating room. Trained circulating nurses supervised by site coordinators
      queried surgical team members about blood contact and collected data on 8502
      surgical procedures from seven community and two university hospitals in 1992.
      Blood contact occurred during 864 cases (10.2% case-contact rate) in 1054 health
      care workers (12.4% person-contact rate). The parenteral exposure (punctures or
      cuts, mucous membranes, nonintact skin) rate was 2.2% and the cutaneous exposure
      (intact skin) rate was 10.2%. Blood contacts were twice as likely to be
      parenteral among surgeons as among other operating room personnel (odds ratio,
      2.0; 95% confidence interval, 1.4 to 2.9). Of cutaneous exposures, 46.9% were
      from unknown sources or were surprise spatters. Logistic regression analyses
      indicated that risk factors associated with any blood contact (parenteral or
      cutaneous) were length of procedure (odds ratio, 1.51; 95% confidence interval,
      1.46 to 1.56), emergency versus scheduled status (odds ratio, 1.44; 95%
      confidence interval, 1.21 to 1.66), selected surgical services, and the hospital.
      Logistic regression analyses of parenteral exposures, as compared with cases in
      which no contact occurred, indicated that risk factors were length (odds ratio,
      1.39; 95% confidence interval, 1.31 to 1.47), thoracic surgery (odds ratio, 2.79;
      95% confidence interval, 2.18 to 3.40), and university hospital versus community
      (odds ratio, 2.26; 95% confidence interval, 1.89 to 2.63). Parenteral exposures
      are clear risks to health care workers; however, it is also important to study
      all contact with blood in the operating room to appreciate potential risks and
      develop appropriate intervention strategies.

PMID- 8267236
TI  - Prolonged contact with blood alters surgical gown permeability.
AB  - INTRODUCTION: Surgical gowns are designed to prevent or minimize transmission of
      blood and pathogens between patients and hospital personnel. During prolonged
      procedures, a gown will probably be presented with repeated challenges of blood
      and other liquids. These multiple insults may alter the fabric's permeability to
      subsequent blood contact. METHODS: In this study, a pressing-leaning simulator
      was used to quantify changes in fabric permeability to blood after surgical gowns
      were prewetted with anticoagulated or coagulating blood. RESULTS: Of the five
      commercially available gowns tested, contact with blood for 1 hr before
      application of an external pressure increased permeability for two gowns,
      decreased permeability for two gowns, and did not alter the permeability of one
      gown (as compared with test conditions in which the fabrics were not prewetted
      with blood). These data indicate that at least in some cases prolonged contact
      with blood increases the amount of blood penetration on application of an
      external pressure, such as may occur during a pressing or leaning motion.
      CONCLUSION: Because increased fabric permeability results in an increased risk of
      skin contact with liquid-borne pathogens for gown users, a major criterion in the
      design and selection of a gown should be its ability to resist blood penetration
      for prolonged periods.

PMID- 8267237
TI  - Role of infection control practitioners in human immunodeficiency virus testing.
      APIC Bloodborne Pathogens Committee.
AB  - BACKGROUND: As a result of the HIV epidemic, the role of the ICP has changed;
      acute care settings have developed a variety of policies regarding patient and
      health care worker (HCW) HIV testing and issues related to the HIV-infected HCW.
      APIC conducted a survey to determine the extent to which ICPs were involved in
      HCW and patient HIV testing and counseling, the prevalence of routine HIV testing
      for patients, institutional policies on HIV testing of patients and HCWs, and the
      management of HIV infected HCWs. METHODS: In 1990, a questionnaire was sent to
      ICPs in a simple random sample of 1300 acute care hospitals (approximately 20%)
      in the United States. RESULTS: Response rate was 52.8%. Of the 686 respondents,
      54.8% provided counseling to the HCW after an exposure incident. ICPs were
      involved not only in HIV testing and counseling for patients and HCWs but also in
      institutional policy development for HIV-related issues. Most facilities (73.8%)
      obtained written consent for testing from the patient after an employee exposure.
      When a direct care giver was known to be HIV positive, 61.5% of the respondents
      evaluated each case individually. CONCLUSIONS: The ICP has a significant role in
      the development and implementation of institutional policies on HIV testing and
      counseling and on the management of HIV-infected workers. These findings affirm
      the need for APIC to provide educational opportunities on the issues related to
      HIV testing and counseling.

PMID- 8267238
TI  - Comparison of a needleless system with conventional heparin locks.
AB  - BACKGROUND: Despite the improvements in needle disposal systems, needlesticks to
      health care workers continue to occur at unacceptably high rates. Needleless
      systems have been shown to reduce the risk of needlesticks. METHODS: This pilot
      study examined the safety of such a system for patients by comparing the rates of
      intravenous infection-related indicators between a conventional heparin lock and
      a needleless system. Patients (n = 97) were categorized on the basis of the
      duration of intravenous placement into 24-, 48-, and 72-hour groups. Within each
      group, half of the patients received conventional heparin locks and half received
      the needleless system. Intravenous infection-related indicators included catheter
      tip culture, adaptor fluid culture, intravenous site erythema, induration and
      tenderness, and elevated oral temperature. RESULTS: Prevalence of one or more
      indicators was 48% for the conventional and 40% for the needleless system, a
      difference that was not statistically significant. CONCLUSIONS: The needleless
      system appeared to pose no greater risk of infection to patients and nurses
      preferred it for its reduced risk of potential needlesticks.

PMID- 8267239
TI  - Salmonella poona infection and surveillance in a neonatal nursery.
AB  - BACKGROUND: This article reports the first known outbreak of Salmonella poona
      infection in a neonatal unit. Three babies had stool cultures positive for the
      organism. At the same time, S. poona was the cause of a nationwide food-borne
      outbreak associated with contaminated canteloupe. To minimize the neonatal
      outbreak, surveys were performed and control measures were instituted. METHODS:
      Epidemiologic surveillance included the culture of rectal swabs collected from 48
      employees, 18 babies, and four family members of the babies. Control measures
      used included the placement in cohorts and isolation of infected babies, strict
      adherence to universal precautions, and the restriction of visitation in the
      nursery. RESULTS: A total of three babies and one employee in the surveillance
      were found to have Salmonella sp. An additional two hospitalized adult patients
      had S. poona. Of all the people included in the surveillance, only the three
      babies were found to have S. poona. The hospital employee had S. enteritidis.
      CONCLUSIONS: Timely culture results, rapid cohort placement of infected babies,
      and strict adherence to universal precautions led to the successful eradication
      of the organism.

PMID- 8267240
TI  - AIDS: problem solving in infection control. Response to the human
      immunodeficiency virus epidemic: solutions from the Centers for Disease Control
      and Prevention and the infection control community.

PMID- 8267241
TI  - The doctor, the asthmatic patient, and the law.

PMID- 8267242
TI  - Food allergy and atopic disease: pathogenesis, diagnosis, prediction of high
      risk, and prevention.

PMID- 8267243
TI  - Pneumocystis carinii pneumonia in an HIV-negative, 8-month-old infant.

PMID- 8267244
TI  - Pollen changes during five decades of urbanization in Tucson, Arizona.
AB  - Five decades of daily pollen measurements have catalogued a growing number of
      imported and native plants in Tucson, Arizona, a city that has a high prevalence
      of allergic rhinitis and asthma. These plants have contributed a large proportion
      of the overall pollen rain and include mulberry, olive, juniper, cypress, privet,
      mesquite, Bermuda grass, ragweed, Palmer's amaranth, and Russian thistle. Factors
      contributing to these increases in pollen include population growth as well as
      changing architectural and landscape preferences. The institution of pollen
      control laws, inner city development, and nonreplacement of allergenic trees
      along with the growing popularity of desert landscaping suggests that trend
      reversal may be occurring.

PMID- 8267245
TI  - Indirect latex contact causes urticaria/anaphylaxis.
AB  - Recurrent urticaria/anaphylaxis is a most perplexing and critical problem, often
      of unknown cause. Though difficult and time consuming, identification of
      causes(s) can be life saving and cost saving for the patient(s). We report a
      complex case of urticaria/anaphylaxis induced by latex allergen in a former
      intensive care unit nurse, in which the allergen contact occurred remotely and
      indirectly by intimate contact with the spouse. Diagnosis of the latex allergy
      was confirmed by epicutaneous skin test in vivo as well as RAST.

PMID- 8267246
TI  - Complications in children with a severe allergy to cow milk.
AB  - A case-comparison study compared the allergic and health complications of
      children who had severe IgE-mediated allergy to cow milk in infancy (study group)
      with those of other atopic children (control group). Severity of clinical atopy,
      IgE sensitization to other allergens, and recurrent episodes of anaphylaxis, as
      well as growth and development were compared in 16 health plan member children
      aged 2 to 18 years with histories of IgE-mediated anaphylaxis and 16 age- and
      gender-matched allergy patients. Data were analyzed using the sign test or the
      signed-rank test of the difference scores of the matched study-control pairs. The
      results showed the study group differed from the control group throughout
      childhood by having more specific allergen sensitizations, atopic dermatitis,
      episodes of sudden severe anaphylaxis, and hospitalizations. Other health
      complications may exist. Medical care of these children should address these
      problems.

PMID- 8267247
TI  - Hospital admissions of young children for status asthmaticus in Honolulu, Hawaii,
      1986 to 1989.
AB  - Asthma admissions of children aged 5 years or younger to the Kaiser Foundation
      Hospital in Honolulu were analyzed for the years 1986-1989. Admissions increased
      at an annual rate of 4.5% during the study period, in agreement with a worldwide
      trend. Most children wheezed before their first admission, but their diagnosis
      was bronchitis rather than asthma. This shows that physicians find it difficult
      to diagnose asthma in young children. Pneumonia was the initial diagnosis in 25%
      of admissions, mainly due to overinterpretation of chest radiographs, and this
      contributed to the overuse of antibiotics. Inpatient treatment with inhaled and
      systemic bronchodilators and anti-inflammatory agents conformed to standard
      practice. Recent adoption of the guidelines by the National Asthma Education
      program and the establishment of an outreach program and asthma register should
      promote more appropriate outpatient treatment and a reduction of admissions for
      asthma.

PMID- 8267248
TI  - Adult sequelae of childhood abuse presenting as environmental illness.
AB  - Sixty-three patients with polysomatic complaints attributed to sensitivity to
      environmental chemicals had detailed clinical assessments and diagnostic
      psychologic evaluations. Objective medical parameters failed to substantiate
      their beliefs that multiple chemicals were the cause of their problems. A group
      of 64 patients with chronic medical conditions and defined psychologic disorders
      not attributed to chemical exposure served as controls. Approximately half the
      patients in each group underwent long-term psychotherapy, and in these patients,
      the prevalence of physical and sexual childhood abuse was significantly higher (P
      < .05) among the cohort of women who attributed their symptoms to environmental
      or chemically related illness. These data suggest that somatization may reflect
      sequelae of childhood abuse and may play an important role in the illness
      experienced by women who believe they are sensitive to environmental chemicals.

PMID- 8267249
TI  - Effect of heating-ventilation-air conditioning system sanitation on airborne
      fungal populations in residential environments.
AB  - Commercial air duct sanitation services are advertised to the public as being
      effective in reducing indoor aeroallergen levels despite the absence of published
      supporting data. Eight residential heat-ventilation-air conditioning (HVAC)
      systems in six homes and seven HVAC systems in five homes in winter and summer,
      respectively, were sampled to determine fungal colony forming units (CFUs) prior
      to and after an HVAC sanitation procedure was performed by a local company. Two
      houses in which no sanitation procedure was performed served as controls in each
      study phase. Two sample sets were obtained at each HVAC system prior to cleaning
      in order to determine baseline CFU levels. The test HVAC systems were then
      cleaned, and the HVAC systems allowed to operate as desired by the residents.
      Posttreatment sampling was performed 48 hours and then weekly after cleaning for
      8 weeks. The HVAC systems were analyzed by exposing sterile 2% malt extract media
      plates at a 90-degree angle to the air flow at the air supply and air return
      vents. The baseline CFUs were similar in the control and study houses. Eight
      weeks after sanitation, the study houses demonstrated an overall CFU reduction of
      92% during winter and 84% during summer. No reduction in CFU values was observed
      over the 8-week study period for the houses selected as controls. Further, HVAC
      sanitation appeared to reduce the number of fungal colonies entering and leaving
      the HVAC system, suggesting that the HVAC contained a significant percentage of
      the total fungal load in these homes. These data suggest that HVAC sanitation may
      be an effective tool in reducing airborne fungal populations in residential
      environments.

PMID- 8267250
TI  - Nonfatal systemic allergic reactions induced by skin testing and immunotherapy.
AB  - Skin testing and immunotherapy with allergens can induce systemic allergic
      reactions. In order to identify factors associated with systemic allergic
      reactions, a prospective study was conducted from 1976-1989 with more than 10,000
      patients being tested and a total of 513,368 injections being recorded. Our study
      showed that the probability of inducing systemic allergic reactions by skin
      testing was less than 0.02% and the probability of systemic allergic reactions
      caused by immunotherapy was 2.9%. The female to male ratio was 3 to 2. The
      highest incidence of systemic allergic reactions was in patients between the ages
      of 16 to 39 years of age. The majority of systemic allergic reactions occurred
      when patients were on increasing doses rather than maintenance doses. More than
      95% of systemic allergic reactions were associated with pollens and most of them
      happened between the concentration of 100 and 1000 PNU/mL. There was no increased
      incidence during grass or ragweed pollination seasons in those patients who
      received grass or ragweed injections during the respective seasons. Only 50% of
      systemic allergic reactions developed within 30 minutes after injections. The
      three most important factors determining the incidence of systemic allergic
      reactions are the type of allergens, the "rate" of increase of allergen
      concentrations, and sensitivity of the patients to allergens. The prick test at
      initial allergy assessment can be used to "rule out," with a high degree of
      certainty, the likelihood of systemic allergic reactions. The prick test is easy
      to perform and it is cost-effective. Prick tests and RAST together are helpful in
      identifying the patients and the allergens at higher risk of systemic allergic
      reactions.

PMID- 8267251
TI  - Sodium metabisulfite and SO2 release: an under-recognized hazard among shrimp
      fishermen.
AB  - Since the introduction of sodium metabisulfite as a food preservative, it has
      been associated with several idiosyncratic reactions (eg, bronchospasm,
      oculonasal symptoms, and urticaria/angioedema) in sulfite-sensitive individuals.
      The pathogenic mechanism of these reactions is not yet understood. We report the
      case of two crewmen on a shrimp trawler who were found dead in the ship's hold.
      Their deaths had occurred while they were applying dry sodium metabisulfite,
      referred to as "shrimp dip" in the shrimping industry. Postmortem examinations
      showed diffuse pulmonary edema consistent with death secondary to asphyxia.
      Associated findings were visceral congestion. Although it is possible to measure
      death from sodium metabisulfite with available records, its potential morbidity
      cannot be estimated. It is known that sodium metabisulfite can react with acids
      and water, releasing toxic sulfur dioxide (SO2) gas. In addition, SO2 gas reacts
      with respiratory tissue forming sulfureous acid, and inducing a pulmonary
      reaction causing hypoxemia. Furthermore, sodium metabisulfite, compared with
      sodium bisulfite, has a much greater propensity to release SO2 gas. We conclude
      that there is a need for improved education regarding the potential side effects
      of sodium metabisulfite, thus eliminating needless occupational morbidity and
      mortality.

PMID- 8267252
TI  - Erroneous peak expiratory flow rates.

PMID- 8267253
TI  - Management of corticosteroid-dependent children exposed to varicella.

PMID- 8267254
TI  - Update on exercise-induced asthma.
AB  - Exercise-induced asthma (EIA) is a temporary increase in airway resistance that
      occurs after several minutes of strenuous exercise, generally eight to 15 minutes
      after the patient has stopped exercising. Some individuals experience a secondary
      reduction in pulmonary function several hours later, the so-called late-phase
      response. Many physicians believe that EIA is caused by respiratory water loss or
      airway cooling. Others incriminate tissue mast cells of the lung. The role of
      histamine is uncertain because it is detected inconsistently in the serum after
      an attack. Recent studies suggest that the release of sulfidopeptide leukotrienes
      may play a major role in EIA. Although the exact pathophysiology has yet to be
      determined, several highly successful treatment regimens have been developed.
      Preventive pharmacologic treatment with aerosolized beta-agonists is more
      successful than treatment with cromolyn sodium; however, coadministration of
      these agents produces significant symptomatic improvement in more than 90% of
      patients. Other useful medications include antihistamines, anticholinergic
      agents, theophylline, oral beta-agonists, calcium channel blockers, alpha
      adrenergic antagonists, nedocromil, and leukotriene antagonists. Exercise-induced
      asthma may be suppressed with warm humidified air. This environment can be
      simulated by swimming in a heated pool or wearing a scarf over the nose and mouth
      in cold weather.

PMID- 8267255
TI  - Pediatric AIDS: clinical, pathologic, and basic science perspective. Introductory
      remarks.

PMID- 8267256
TI  - Neurologic syndromes.
AB  - It is now well recognized that HIV-1 associated CNS disease may complicate the
      course of HIV-1 infection and AIDS in infants and children. It is also well
      recognized that the neurologic dysfunction in these young patients adds
      significantly to the morbidity of the disease and is often a devastating
      complication. It is apparent that HIV-1 CNS infection in infants and young
      children is complicated by numerous developmental issues. The effects, direct and
      indirect, of HIV-1 on the developing nervous system must be considered. The
      effects of HIV-1 on the immature immune system must also be considered. Moreover,
      the possible effects of HIV-1 on the many complex interactions between these two
      systems during development will clearly also require investigation. In order to
      care for these children and to design rational approaches for treatment and
      prevention, it is now critical to develop a better understanding of how HIV-1
      affects the developing nervous system.

PMID- 8267257
TI  - Reliability of neurologic assessment in a collaborative study of HIV infection in
      children.

PMID- 8267258
TI  - Maternal transmission and diagnosis of human immunodeficiency virus during
      infancy.

PMID- 8267259
TI  - Assessing neurobehavioral changes in HIV+ infants and children. A methodological
      approach.
AB  - The rationale and development of a developmental approach to assessing
      neurobehavioral changes in infants and children exposed to or infected with the
      HIV-1 virus is presented. Methodological problems in earlier approaches to
      assessment are reviewed. Among these are measures employed, impact of different
      treatments on measures of outcome, multicultural differences between samples, and
      analytic approaches to developmental data. The assessment protocol developed by
      the Pediatric Neurobehavioral Study Group of NIMH/NICHD/NIAID is described.

PMID- 8267260
TI  - Opportunistic infections in pediatric HIV disease.

PMID- 8267261
TI  - Antiviral therapy for HIV infection in infants and children.

PMID- 8267262
TI  - The clinical evaluation of cytokines and immunomodulators in HIV infection.

PMID- 8267263
TI  - Prospects for prevention of vertical transmission of human immunodeficiency virus
      by immunization.

PMID- 8267265
TI  - Tissue culture models of HIV-1 infection.

PMID- 8267264
TI  - Human immune development: implications for congenital HIV infection.

PMID- 8267266
TI  - Animal models for perinatal transmission of pathogenic viruses.
AB  - In earlier work, mouse models have been used to demonstrate the efficacy and lack
      of toxicity of transplacental and perinatal AZT therapy. These practical small
      animal models can be useful for evaluating antiviral drugs aimed at common
      retroviral functions only, since Type C MuLVs are used. A primate model for fetal
      infection with an immunosuppressive lentivirus, SIV, has been established using
      ultrasound-guided inoculation of the amniotic fluid. The infection rate was 86%
      overall and 100% if the fetal SIV exposure occurred at least 19 days before
      delivery. The suspected major route of vertical HIV-1 transmission, that is,
      virus entry through fetal mucous membranes or skin, is replicated by our
      approach. The high fetal infection rate will allow studies of SIV pathogenesis
      during various stages of fetal development. This model should be well suited to
      development and evaluation of therapeutic strategies for preventing fetal
      infection.

PMID- 8267267
TI  - AIDS and the central nervous system. Examining pathobiology and testing
      therapeutic strategies in the SIV-infected rhesus monkey.

PMID- 8267269
TI  - A controlled study of cognitive and language function in school-aged HIV-infected
      children.

PMID- 8267268
TI  - Maternal drug use in perinatal HIV studies. The Women and Infants Transmission
      Study.

PMID- 8267270
TI  - Elective pregnancy terminations and HIV-1.

PMID- 8267271
TI  - Use of PCR for detection of HIV-1 sequences in babies born to seropositive
      mothers.

PMID- 8267272
TI  - Diagnosis and quantitation of HIV-1 infection in infants and children by whole
      blood culture.

PMID- 8267273
TI  - HIV-specific IgG3 in cord blood. Predictive value for seroreversion.

PMID- 8267274
TI  - A rapid, sensitive, PCR-based method for detection of HIV-1 specific nucleic acid
      in the culture supernatant of infected cells.

PMID- 8267275
TI  - HIV-1 specific IgG capture enzyme immunoassay to study the dynamics of HIV-1
      antibody and to diagnose HIV-1 infection in infants. NYC Perinatal HIV
      Transmission Collaborative Study Group.

PMID- 8267276
TI  - Detection of HIV-1 IgA by an IgA capture enzyme immunoassay for early diagnosis
      in infants. NYC Perinatal HIV Transmission Collaborative Study Group.

PMID- 8267277
TI  - Indeterminate western blot in children who serorevert for HIV.

PMID- 8267278
TI  - Analysis of the HIV-1 envelope V3-loop sequences from ten mother-child pairs.

PMID- 8267279
TI  - The presence of cryptococcal capsular polysaccharide increases the sensitivity of
      HIV-1 coculture in children.

PMID- 8267280
TI  - HCV vertical transmission in infants born to HIV-HCV seropositive mothers.

PMID- 8267281
TI  - Preliminary data on Chlamydia pneumoniae seroprevalence in HIV-1 infected
      children.

PMID- 8267282
TI  - Mycobacterium avium complex in HIV-infected children.

PMID- 8267283
TI  - Peripheral B-cell activation and immaturity in HIV-infected children.

PMID- 8267284
TI  - Central nervous system in pediatric AIDS. Results from Neuropathologic Pediatric
      AIDS Registry.

PMID- 8267285
TI  - Administration of aerosolized pentamidine to HIV-infected infants.

PMID- 8267286
TI  - Pharmacokinetics of trimetrexate glucuronate in infants with AIDS and
      Pneumocystis carinii pneumonia.

PMID- 8267287
TI  - Evaluation of anti-HIV agents in vitro by quantitative PCR.

PMID- 8267288
TI  - Immunoregulation of tumor necrosis factor production by HIV-1 gp-120 in neonates
      and adults.

PMID- 8267289
TI  - Different strains of HIV-1 infect distinct human fetal neural cells.

PMID- 8267290
TI  - Productive infection of human fetal microglia in vitro by HIV-1.

PMID- 8267291
TI  - HIV infection of human cortical neuronal cells. Enhancement by differentiating
      growth factor.

PMID- 8267292
TI  - Neural cell receptor for HIV-1. Initial biochemical characterization.

PMID- 8267293
TI  - HIV-1 mRNA transcripts from persistently infected human fetal astrocytes.

PMID- 8267294
TI  - Epidemiology of pediatric human immunodeficiency virus infection in the United
      States.
AB  - HIV infection is an important cause of morbidity and mortality in the pediatric
      population. Providers of health care to children need to be aware of the problem
      and the characteristics of the most affected populations. Early diagnosis of HIV
      infection is critical for initiating appropriate antiviral therapy and
      prophylactic treatment for opportunistic infections. Attending to the myriad of
      social problems these families face is equally important for providing an optimal
      chance for prolonged survival and a reasonably high quality of life.

PMID- 8267295
TI  - Reservoirs of HIV infection or carriage: monocytic, dendritic, follicular
      dendritic, and B cells.

PMID- 8267296
TI  - Pathology of pediatric AIDS. Overview, update, and future direction.

PMID- 8267297
TI  - Antibody in human immunodeficiency virus infection.

PMID- 8267298
TI  - Central nervous system pathology in pediatric AIDS.
AB  - Children with AIDS frequently have neurological manifestations due to
      complications of immunodeficiency or intrinsic effects of human immunodeficiency
      virus type 1 (HIV-1) on the central nervous system (CNS). The most common
      neurological disorders not directly related to HIV-1 infection include
      cerebrovascular disease and lymphoma. Global anoxic-ischemic and necrotizing
      encephalopathies are frequent, while CNS hemorrhages and arteriopathies are less
      frequent. Opportunistic CNS infections are uncommon, limited predominantly to
      monilial and cytomegaloviral encephalitides. Only a few cases of CNS
      toxoplasmosis have been reported in children. CNS lymphomas often occur in the
      setting of systemic polymorphous, polyclonal B-cell proliferations that have been
      associated with Epstein-Barr virus infection. Intrinsic effects of HIV-1 on the
      CNS include microcephaly, diffuse gliosis, basal ganglia mineralization, HIV
      encephalitis, and corticospinal tract degeneration. Although viral antigens can
      be detected in microglia and multinucleated cells in HIV encephalitis, most of
      the CNS effects of HIV-1 infection cannot be attributed to detectable levels of
      viral antigen, suggesting that the pediatric CNS is unusually susceptible to low
      level HIV-1 infection or to systemic effects of HIV-1 infection, possibly
      mediated by soluble factors, including the inflammatory cytokines, interleukin-1
      beta, and tumor necrosis factor-alpha, which have been shown to be increased in
      serum and cerebrospinal fluid of children with AIDS.

PMID- 8267299
TI  - Epidemiology of childhood obesity. A national perspective.

PMID- 8267300
TI  - Do media influence childhood obesity?

PMID- 8267301
TI  - Target marketing of food products to ethnic minority youth.

PMID- 8267302
TI  - Physical activity in the prevention of childhood obesity.

PMID- 8267303
TI  - Project SPARK. Effects of physical education on adiposity in children.
AB  - Project SPARK evaluates multiple effects of a health-related physical education
      (PE) program for elementary school students. Seven schools were randomly assigned
      to one of three conditions: usual PE or control, trained classroom teachers, or
      PE specialists. The intervention was implemented throughout the fourth and fifth
      grades. Data are available from one cohort of 550 children who were measured in
      the fall and spring of both grades. Adiposity was assessed by triceps and calf
      skinfolds, and body mass index (BMI) was also measured. Data at each measurement
      point were analyzed by ANOVAs, covarying for baseline values. At no measurement
      point were there significant group differences in total skinfold. At both fifth
      grade measurement points for boys and girls, however, there was a trend for the
      control group to have higher skinfold values than the two intervention groups. At
      the final measure, the difference between the highest and lowest groups was about
      3 mm for girls and 2 mm for boys. BMIs were significantly lower at some
      measurement points for boys and girls, but this could be due to increased lean
      body mass in intervention students. After two years, there was a trend for the
      children exposed to the PE intervention to have lower levels of body fat, but the
      differences were not significant.

PMID- 8267304
TI  - Primary prevention of obesity in Mexican-American children.

PMID- 8267305
TI  - The role of the family in obesity prevention and treatment.

PMID- 8267306
TI  - School-based obesity prevention. Population versus high-risk interventions.

PMID- 8267307
TI  - Primary prevention of obesity in American Indian children.

PMID- 8267308
TI  - Energy expenditure and the development of early obesity.

PMID- 8267309
TI  - Recent advances in the treatment of childhood obesity.
AB  - The multidisciplinary, four-phase approach, which includes PSMF, BEM, and MPE is
      successful in treating mild, moderate, and severe degrees of childhood and
      adolescent obesity. The MPE program is appropriate for use with PSMF and BEM due
      to its progressive nature, variety of options, and moderate intensity level. In
      addition, the MPE program is of sufficient intensity, duration, and frequency to
      promote a significant increase in estimated aerobic capacity (VO2max) and to
      promote the maintenance of lean body mass and resting energy expenditure. The
      short-term intervention of PSMF, BEM, and MPE also results in an improvement in
      body composition, lipid profiles, and IGF-1 and T3 levels. The 1200-calorie
      balanced diet, MPE, and BEM also provide a successful method of weight
      maintenance in children and adolescents, as indicated by further improvement in
      body composition at the 26-week measure. Additional studies are needed to assess
      the contribution of exercise to the maintenance of lean body mass and resting
      energy expenditure in obese children and adolescents. In addition, it will be
      important to assess long-term weight maintenance in obese adolescents who
      effectively lose weight in this multidisciplinary program.

PMID- 8267310
TI  - Binge-eating disorder in obese adolescent girls.
AB  - Thirty percent of 51 obese adolescent girls seeking treatment for their obesity
      engaged in binge eating. Two psychometric measures, "disinhibition" and
      "happiness and satisfaction" predicted 63% of the variance in severity of binge
      eating. There was no difference in the history of dieting between obese subjects
      who binged and those who did not.

PMID- 8267311
TI  - Treatment of childhood obesity in pediatric practice.
AB  - Evaluation of obese children and adolescents in the pediatric office or clinic
      should include baseline assessment of weight for height, and body fatness; should
      rule out endocrine and genetic causes of obesity; and should evaluate other
      cardiovascular risk factors. Treatment of obesity is most successful if realistic
      goals are set; if a safe rate of weight loss of one to two pounds per week can be
      achieved through a reduction of caloric intake that amounts to 500 calories less
      per day; if increased physical activity is stressed as much as diet; if parental
      support is strong; and if behavior therapy is provided during the course of
      treatment to help both child and parent achieve the diet, exercise, and behavior
      goals.

PMID- 8267312
TI  - Adolescent obesity and cardiovascular risk: a rational approach to management.
AB  - Ten obese adolescents, referred because of elevated cardiovascular disease risk,
      were treated in a pediatric atherosclerosis prevention center. The focus of
      treatment was an increase in exercise tolerance and aerobic capacity and a
      decrease in the percentage of fat in the diet. Weight loss was not a goal of
      treatment, but continued growth with a slowing of the rate of weight gain was
      emphasized. All patients were at elevated cardiovascular risk at the entry to the
      study, and nine of the ten had significant improvements in one or more of their
      cardiovascular risk parameters. Furthermore, with regard to body composition,
      eight of the ten patients were able to improve their body mass index. On average,
      triceps skinfold thicknesses declined 25 percent. Total cholesterol declined 14%,
      triglycerides declined 33%, LDL cholesterol declined 13%, and HDL cholesterol did
      not change with this form of treatment. As for systolic and diastolic blood
      pressure, four of the ten patients who had elevated blood pressures at the
      initiation of treatment were able to decrease their blood pressure, in absolute
      terms and on the basis of their percentiles for age and sex. We conclude that, in
      obese adolescents, improved diet and body composition, a slowed rate of weight
      gain, and a reduction of cardiovascular risk shown through lipid profiles and
      blood pressures can be achieved from a multidisciplinary treatment program
      focused on achievable goals. These goals include (1) increased habitual exercise
      and increased aerobic exercise and (2) a decrease in the percentage of energy
      intake from fat and saturated fat, with a concomitant decrease in the balance of
      energy intake to energy output. It is important to remember that we did not focus
      on weight loss per se and that the treatment was individualized to the
      developmental stage of the adolescent.

PMID- 8267313
TI  - Fear of obesity in childhood.

PMID- 8267314
TI  - Methodological issues and ten-year outcomes for obese children.
AB  - In our research we have shown that obese children can lose weight and maintain
      this change in body composition over extended periods throughout development.
      Treatment variables that are important include having the parents as active
      participants in the treatment of their children and including exercise programs
      along with diet. The motivational structures within the family that support or
      discourage behavior change, however, may be as important as the specific
      behaviors that we attempt to modify. For example, we have observed successful
      long-term outcome in families in which we have used conjoint or reciprocal
      contracts, but not in families in which the child alone was targeted for behavior
      change. The specific methodology for including parents and children in treatment
      may be important, or it may just be important for both parents and children to be
      targeted for change and family members taught to support the behavior change of
      the other family members. Future research with children should pay attention to
      methods that mobilize family support for behavior change in multiple family
      members and strive for methods that will modify the sources of support for the
      targeted child, which will generalize to other family members.

PMID- 8267315
TI  - Ten-year trend of energy intakes of American children ages 2-10 years.

PMID- 8267316
TI  - Altered immune function in a morbidly obese pediatric population.

PMID- 8267317
TI  - Initial experience with long-term inpatient treatment for morbidly obese children
      in a rehabilitation facility.

PMID- 8267318
TI  - Genetic aspects of obesity.

PMID- 8267319
TI  - Early frequent treatment in prevention of childhood obesity. How we do it.

PMID- 8267320
TI  - Obesity in preschool and school-age children. Early frequent treatment is best.

PMID- 8267321
TI  - The Southwestern Cardiovascular Curriculum Project.

PMID- 8267322
TI  - Cayuga-Tompkins Healthy Heart Program.

PMID- 8267323
TI  - Physicians' perceptions of childhood and adolescent obesity.

PMID- 8267324
TI  - Hyperinsulinemia: incidence and risk in an obese pediatric population.

PMID- 8267325
TI  - Impacting on pediatric obesity. The California model.

PMID- 8267326
TI  - Energy expenditure and intake in obese and nonobese African-American girls.

PMID- 8267327
TI  - Methodological issues in estimating the prevalence of obesity in childhood.

PMID- 8267328
TI  - A comprehensive protocol for assessment of obese adolescents and evaluation of
      their progress in managing weight.

PMID- 8267329
TI  - Factors associated with obesity in preschool children.

PMID- 8267330
TI  - The relationship between self-esteem and depression in obese children.
AB  - It has been suggested that obese children have increased problems with self
      esteem and depression when compared to the normal pediatric population. Fifty-one
      consecutive patients enrolled in a hospital based weight management program
      received the CDI and the PHSCS as part of their initial evaluation. There were 24
      males and 27 females with ages ranging from 5-17 years and BMI (kg/m2) of 22-63
      (mean 33.3). Results of the CDI were classified into three groups. Children with
      CDI scores greater than 13 were classified as depressed (n = 16). Scores between
      9 and 12 were considered borderline depression (n = 11). Scores less than 9 were
      considered normal (n = 24). The children in the depressed and borderline groups
      were significantly different from the children in the normal group in their level
      of self-esteem. As depression increased, self-esteem decreased, indicating an
      inverse relationship between self-esteem and depression. Depressed and borderline
      depressed children were also more anxious (i.e., nervous, worried) and had more
      perceived behavior problems (increased frequency of punishment, difficulty
      obeying orders) than the normal group. They also had fewer interests in school
      and felt their physical appearance was not acceptable. The depressed group's
      scores were significantly lower on the happiness and popularity scales of the
      PHSCS than the normal group. Scores on the CDI did not correlate with age, race,
      sex, Tanner stage, socioeconomic status, or body mass index. In this study obese
      pediatric patients showed significant depression and lowered self
      esteem.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267331
TI  - An effective multidisciplinary approach to weight reduction in youth.

PMID- 8267332
TI  - Food and nutrition messages in film. A preliminary content analysis.

PMID- 8267333
TI  - Evaluation of dietary and activity questionnaires for elementary school children.

PMID- 8267334
TI  - Obesity in children: a risk for depression.

PMID- 8267335
TI  - Fetal hyperinsulinism in offspring of diabetic mothers. Association with the
      subsequent development of childhood obesity.

PMID- 8267336
TI  - Hemodynamic and cardiac consequences of childhood obesity.

PMID- 8267337
TI  - Influences on the eating behavior of children.

PMID- 8267339
TI  - Obesity prevention and macronutrient intakes of children in the United States.

PMID- 8267338
TI  - Methodological considerations in the assessment of childhood obesity.

PMID- 8267340
TI  - Ethnicity and obesity development in children.

PMID- 8267342
TI  - The high cost of high tech medicine.

PMID- 8267341
TI  - Obesity and cardiovascular risk in children.

PMID- 8267343
TI  - Percutaneous radiologic drainage of pelvic abscesses.
AB  - Several radiologically-guided approaches to drainage of pelvic abscesses have
      been described in recent years. Previously, surgery was deemed the only option in
      many such cases. We employed these radiologic techniques in a heterogenous group
      of 32 patients. Ten patients in this group were drained by the transgluteal
      route; 12 transrectally (one transvaginally also) and ten via the presacral
      route. Twenty-four patients had abscess formation as a complication of recent
      abdomino-pelvic surgery; eight from other causes. Six patients had multiple
      abscesses. Technical success was achieved in 28/32 (88%) patients. No
      periprocedural complications were noted. Thirty-day mortality was 9% (three
      patients). Twenty-one patients (65%) improved clinically post procedure; 16 of
      them had no further surgical intervention. Five patients had surgery to treat
      underlying disease. Of the seven patients who did not improve, five underwent
      surgical drainage of whom two died from multi-organ failure. Three had successful
      surgery (one combined with further radiologic drainage). One patient had a second
      percutaneous drainage and the remaining patient died. The pelvic location of an
      abscess or collection should not preclude radiologically-guided drainage and
      clinicians should be aware of these techniques.

PMID- 8267344
TI  - Benign ureteric strictures--management by percutaneous interventional uro
      radiological techniques.
AB  - Nineteen patients with benign ureteric strictures were treated by an antegrade
      approach. Following percutaneous nephrostomy, the strictures were dilated by
      either tapered dilating catheters or angiographic balloon catheters and
      temporarily stented using internal double J ureteral stents. The strictures were
      most commonly caused by calculous disease, post-radical hysterectomy and
      inflammatory disease, including tuberculosis and candidiasis. The majority (73%)
      were situated in the distal third of the ureter. Short strictures less than 3 cm
      in length were present in eight patients (36%) while in ten patients the age of
      the stricture was less than three months. In two patients, the strictures were
      too severe and could not be crossed by guidewires and those patients required
      reimplantation of the ureter. In 16 patients, the strictures were successfully
      dilated. Follow-up period ranged from five months to twenty-six months (mean 13
      months). There were no complications directly related to dilatation. The
      aetiology and age of an ureteric stricture are the most important factors in
      predicting the success of ureteric dilatation. This review demonstrates that
      early treatment of strictures by percutaneous techniques, even those that may be
      devascularised by the underlying disease process, should usually be successful.

PMID- 8267345
TI  - Retrograde penile venoablation.
AB  - We evaluated retrograde penile venoablation as treatment modality in impotent
      patients suffering from a venous leakage. Forty-six of 53 (86%) interventions
      were technically feasible. Improvement in erectile function was obtained by 24/46
      (52%) procedures: in 20 men spontaneous intercourse was possible, four men needed
      additional intracavernous injection of vasoactive drugs. In 11 patients, potency
      deteriorated between one and 20 months after the venoablation; in seven, potency
      could be improved by repeated embolization. Potency of 13 patients is unchanged
      one to 30 months (average 10.5 months) after the intervention. Complications were
      not observed.

PMID- 8267346
TI  - Defecating proctography: local experience.
AB  - Between October 1990 to November 1991, defecating proctography was performed on a
      select group of patients with complaints of persistent constipation or sensation
      of incomplete evacuation. Out of the 27 patients studied, a high percentage
      (88.8%) showed some form of anatomical or functional abnormality of the
      defecating mechanism. As defecating proctography is a relatively new mode of
      investigation locally, we briefly describe our method and results. These include
      rectocele formation, intrarectal mucosal prolapse, intussusception and pubo
      rectalis paradox. Some of these cases may be amenable to surgical correction.

PMID- 8267347
TI  - The role of the radiologist in liver transplantation.
AB  - The radiologist is an important member of the liver transplant team. His main pre
      operative role is to detect abnormalities which may preclude transplantation or
      alter the standard surgical approach in patients. Colour Doppler ultrasound and
      computerised tomography (CT) are the primary imaging methods utilised pre
      operatively. Knowledge of the surgical procedure employed is essential and
      comprises four basic vascular anastomoses, namely: supra- and infra- inferior
      vena cava, portal vein and hepatic artery. In the immediate post-transplant
      period, hepatic artery thrombosis is the most common vascular complication. The
      radiologist plays a major role in the diagnosis and management of vascular and
      biliary complications, as well as the assessment and treatment of fluid
      collections. The current status of imaging graft rejection remains uncertain.
      Doppler ultrasound and direct cholangiography are the most frequent post
      operative investigations. Emphasis is placed on early radiological evaluation of
      complications leading to graft failure, patient morbidity and mortality, so as to
      enable institution of the appropriate surgical or radiological interventional
      procedure.

PMID- 8267348
TI  - Percutaneous ultrasonic angioplasty: initial results of an in-vitro study on
      normal and atherosclerotic human vessel segments.
AB  - The aim of the present study was to assess the efficacy and safety of a new
      ultrasound catheter system in vitro before employing it in humans. Ultrasound
      energy was applied to 141 normal and atherosclerotic human vessel segments,
      obtained at autopsy. Macroscopical and histological examination of the treated
      vessel segments revealed that ultrasound energy is atraumatic to the normal
      vessel wall. In atherosclerotic vessel segments, there was macroscopically
      significant reduction in the size of plaques. In 7/10 completely occluded femoral
      arterial segments, recanalization could be achieved. The resulting lumen
      approximated the diameter of the wire probe. Therefore, ultrasound energy is an
      appealing form of energy for recanalization of completely obstructed
      atherosclerotic vessels and for disintegration of atherosclerotic plaques.
      Clinically, ultrasonic angioplasty may become an adjunctive modality to balloon
      angioplasty.

PMID- 8267349
TI  - Neuroblastoma and diagnostic imaging.
AB  - To assess the utility of the current imaging modalities, a six-year retrospective
      study was conducted from May 1985 through April 1991 on 11 patients with
      histopathologically confirmed neuroblastoma. There were four males and seven
      females. Median age at presentation was six years. All patients underwent
      intravenous urography (IVU), abdominal ultrasonography (US), skeletal surveys and
      bone marrow aspiration. Computed tomographic (CT) scanning was performed in nine
      patients and trephine bone biopsy in five. Suprarenal gland was the primary site
      in six patients, including one bilateral neuroblastoma. Two presented with
      primary paraspinal mass, one with posterior mediastinal mass, one had a
      retroperitoneal tumour and one presented as primary cerebral neuroblastoma. IVU
      showed indirect evidence of suprarenal tumours in five patients. US demonstrated
      suprarenal mass in six and calcification within the mass in five patients. US
      also documented retroperitoneal lymphadenopathy in five patients. US-guided fine
      needle aspiration biopsy was performed in seven patients and it gave correct
      histological diagnosis in all. CT accurately depicted all the primary tumours and
      their involvement of the surrounding structures and metastases in the brain and
      orbits. US proved to be quite accurate in diagnosing primary abdominal tumours
      despite its limitations but in other sites, CT was of greater help. Solid
      appearance of a suprarenal mass on US made the diagnosis of neuroblastoma very
      likely and calcification within the mass further supported the diagnosis.

PMID- 8267350
TI  - Venous sampling: its role in localization of endocrine tumours.
AB  - Despite recent instrumentation advancement in morphologic imaging, venous
      sampling remains a sensitive physiological investigation for functional
      localization of hormonal hypersecretion. The test requires technical expertise
      and reliable laboratory support, and should be selectively applied to address
      individual clinical problems in coordination with other imaging modalities.
      Depending on the venous anatomy, sampling may achieve regional localization or
      lateralization of the endocrine tumour. Adrenal venous sampling serves to
      lateralize functioning tumour, and to differentiate it from hyperplasia. Inferior
      petrosal sinus sampling confirms pituitary Cushing's disease and lateralizes the
      adenoma. Systemic venous sampling identifies the site of ectopic hormonal
      secretion. In the localization of pancreatic islet cell tumours, the test is
      further enhanced by sampling after intraarterial injection of hormonal
      secretagogue. The experience of venous sampling in a regional referral hospital
      is discussed, including the patient selection, its technical details, pitfalls
      and effectiveness in achieving tumour localization for patient management.

PMID- 8267351
TI  - Use of skeletal surveys in the radiological assessment of renal osteodystrophy--a
      study in the Singapore General Hospital.
AB  - The aims of this review on the use of skeletal surveys in the radiological
      assessment of renal osteodystrophy were threefold: to describe the radiological
      pattern of renal osteodystrophy in a local cohort of patients with chronic renal
      failure, to assess whether serial radiographs of the hands may effectively
      replace full radiological skeletal surveys in the long-term follow-up assessment
      of renal bone disease, and to formulate a grading system for bone resorption due
      to hyperparathyroidism. A radiological study of 61 patients with chronic renal
      failure revealed 20 (32.8%) patients with unequivocal radiological signs of renal
      osteodystrophy. The main abnormal radiological features observed in descending
      order of frequency were: osteopenia with associated cortical thinning and
      coarsened bone trabecular pattern (75%), subperiosteal resorption (60%),
      osteosclerosis (50%), extraosseous calcification (30%) and periosteal new bone
      formation (15%). A five-grade method of assessing the severity and extent of bone
      resorption was formulated. The study showed that 40% of the patients with a
      radiological diagnosis of renal osteodystrophy did not show changes in the hand
      radiographs. This finding precluded a recommendation of hand radiographs being
      used alone in the long-term radiological follow-up of patients with renal bone
      disease. An alternative was proposed and this was a limited radiological skeletal
      survey of three projections: radiographs of both hands, chest including the
      clavicles and the pelvis. This limited study would result in a cost saving of 62%
      as compared to a full study.

PMID- 8267352
TI  - Use of magnetic resonance imaging in the evaluation of nasopharyngeal cancer.
AB  - Computerised tomographic (CT) scanning is an established modality in the
      diagnosis and evaluation of tumours of the nasopharynx. Magnetic resonance (MR)
      imaging is a newer tool which has rapidly gained acceptance in the same regard
      due to its innate ability to better characterise and detail soft tissue
      structures, and its multiplanar scanning ability. This study reviews our
      experience, in a series of 30 cases, with the use of MR imaging in lesions of the
      nasopharynx, in particular nasopharyngeal carcinoma. Most of our patients showed
      involvement of the pharyngeal mucosal and parapharyngeal spaces, as expected. A
      large number also had intracranial extension. Our sample was probably biased as
      patients with neurological involvement are more likely to be assessed by MR than
      CT. Soft tissue infiltration, particularly intracranial extension, was very
      clearly delineated, especially when intravenous contrast (gadolinium DTPA) was
      administered. Bone erosion was not well demonstrated. In current clinical
      practice where radiotherapy is the most common form of treatment for
      nasopharyngeal carcinoma however, there does not in general, appear to be any
      clear advantage of MR over CT in the imaging of this particular disease, although
      there are some exceptions.

PMID- 8267353
TI  - Penile angiography in impotence: local experience.
AB  - Vasculogenic causes of impotence and especially venous leakage are now considered
      to be significantly worthwhile to be evaluated in the light of new developments
      and changes in the treatment of erectile dysfunction. The investigations of
      cavernosography and penile arteriography are gaining importance. In 32 months,
      from August 1990 to March 1993, 126 cavernosograms and 11 bilateral internal
      pudendal arteriograms have been performed on patients from Toa Payoh Hospital.
      Smooth muscle relaxants are helpful in both procedures. Nearly three-quarters of
      the cavernosograms showed deep venous leakage. The use of arteriograms is still
      very restricted. The many variations of the arterial supply to the penis pose
      problems in the interpretation of the arteriograms and hence, recognition of the
      numerous variations besides the knowledge of the normal basic vascular anatomy is
      of paramount importance.

PMID- 8267354
TI  - Subarachnoid spaces in infants and young children.
AB  - In computed tomography of young children, the frontal subarachnoid spaces were
      sometimes noted to be prominent in scans which were otherwise normal. These
      apparently enlarged spaces raise the suspicion of possible subdural hygromas. The
      objective of this study is to show the trend and variability of the intracranial
      subarachnoid spaces, especially the frontal subarachnoid spaces with age in
      children. Computed tomographic scans of 39 children up to five years of age with
      normal head scans were assessed for sizes of the subarachnoid spaces which were
      subjectively graded from I to V. Grade I is not visible while grade V is
      borderline enlargement. The sizes of the subarachnoid spaces were found to be
      more variable in those below the age of two years, with a tendency to be larger
      compared to older children. Based on these observations, prominent subarachnoid
      spaces in those below the age of two years should be considered a normal variant.
      A diagnosis of subdural hygroma must, therefore, be made with caution.

PMID- 8267355
TI  - Cerebral venous angioma--a misnomer?
AB  - Cerebral venous angioma (CVA) is an embryonic venous malformation. Its incidence
      was thought to be radiologically rare previously but with greater clinical
      awareness, the routine use of contrast enhanced computerised tomography (CECT)
      and the increasing availability of magnetic resonance imaging (MRI), it is no
      longer perceived to be a rare lesion. In fact, it is the commonest intracranial
      vascular malformation seen at autopsy. We report our experience of 15 patients
      with cerebral venous angiomas, 14 of whom had their lesions confirmed by cerebral
      angiography. Presentation was variable and non-specific. The commonest presenting
      symptom was headache (n = 7). Other clinical presentations included epilepsy (n =
      5), intracerebral bleed (n = 4, two were thought to be due to an associated
      cerebral cavernous angioma and one was due to a ruptured arteriovenous
      malformation) and non-specific giddiness (n = 3). Six were diagnosed
      incidentally. Based on the angiographic findings and the relatively benign
      clinical course in the majority of our patients, we believe that CVA is a
      developmental anomaly and should not be excised routinely.

PMID- 8267356
TI  - Comparison of accuracy of magnetic resonance angiography with conventional
      angiography: a report of 45 cases.
AB  - To investigate the accuracy of magnetic resonance angiography (MRA), compared to
      conventional cerebral and carotid angiography (CA), 45 patients underwent MRA
      within one week after CA. The MRA involves a FISP (fast imaging steady
      precession) pulse sequence base on three-dimensional time-of-flight phenomena at
      1.0 Tesla. Repetition time of 35-40 msec, echo time of 7-11 msec and a flip angle
      of 15-25 degrees were used to optimise the depiction of blood flow as high
      intensity. Volume data were then submitted to a maximum intensity projection
      programme and viewed at multiple arbitrary projection angles rotating through the
      three orthogonal planes. Venous structures were suppressed with a presaturation
      slab superior to the area of interest. All significant stenoses and occlusions at
      the carotid bifurcation and circle of Willis were detected. Other than the
      carotid siphon (61.4%), the rest of the arteries have above 70% complete
      agreement between MRA and CA. The carotid bifurcation and basilar artery show
      complete agreement of 75.4% and 76.2% respectively, making MRA a simple sensitive
      screening procedure. This report shows that MR angiography has an important role
      in the evaluation of blood flow in the head and neck regions.

PMID- 8267357
TI  - Cerebrovascular applications of magnetic resonance angiography.
AB  - Magnetic resonance angiography (MRA) has been applied to a variety of different
      manifestations of cerebrovascular disease to date. Practically, the limitations
      of these techniques must be taken into account such that the appropriate method
      is applied to answer a specific clinical question and the acquisition parameters
      are chosen to maximise the sensitivity and specificity of the study. Based upon
      these results, it must be decided whether the conventional parenchymal MR and MRA
      evaluations are sufficient in a particular setting or whether it is necessary to
      commit the patient to a more traditional, invasive angiographic study for a more
      thorough investigation. Presently, MR angiographic studies and flow measurement
      techniques serve to compliment the more traditional spin-echo evaluation of
      patients with small aneurysms, arterial and venous occlusions, vascular
      malformations and in some cases of neoplastic vascular invasion. With well
      trained technicians and carefully prescribed protocols, this new information and
      improved diagnostic sensitivity can be used routinely with only a minor increase
      in patient exam time.

PMID- 8267358
TI  - Review of the role of magnetic resonance imaging in acute cervical spine
      injuries.
AB  - Cervical spine injury is often catastrophic and neurologic deficits that often
      accompany it commonly leave the victim permanently disabled. Radiology has always
      played a pivotal role in diagnosing, assessing and prognosticating these
      injuries. For decades, conventional radiography, tomography and cervical
      myelography have been the only modalities available. With the advent of computed
      tomography, the first major revolution in radiology occurred. For the first time,
      bony injury could be clearly defined in the axial plane and the cross-sectional
      anatomy studied. Magnetic resonance imaging has strengthened the radiological
      armamentarium. The spinal cord itself and the soft tissues of the neck can now be
      imaged directly.

PMID- 8267359
TI  - Basic properties and results of clinical trials of ultrasound contrast agents
      based on galactose.
AB  - The development of reproducible echogenic contrast agents, which contain
      physiologically degradable acoustic strays in micrometre dimensions, has been
      under way for several years; all currently known industrial echocontrast agents
      are based on microbubbles, due to their special acoustic properties. The
      currently known echogenic contrast agents can be divided into three physically
      different types: microbubble-containing liquids, gas-filled microspheres and
      microbubble-containing suspensions (e.g. SH U 454-Echovist and SH U 508 A). The
      agents SH U 454 and SH U 508 A are based on galactose microparticles, which are
      suspended shortly before use. After intravenous injection, SH U 454 dissolves
      after leaving the right heart before the left heart is reached. SH U 508 A
      displays greater intravascular stability than SH U 454 and leads to an increase
      of the echogenicity in the blood which, after intravenous injection, survives
      pulmonary transit and reaches the arterial vascular bed. This indicates that the
      microbubbles are stable under physiological pressures. After intravascular
      dissolution of the microstructures, the remaining galactose (a monosaccharide
      with no known allergenic potential) is degraded physiologically. To date, a total
      of more than 2,500 patients has been examined in clinical trials with SH U 454
      (Echovist). The intravenous administration of this contrast agent was well
      tolerated; in particular, no substance-induced severe adverse events were
      observed, and no clinically relevant changes of cardiovascular function or of
      laboratory parameters occurred. Extensive clinical experience has been gained in
      the main indications echocardiography (> 1,850 patients), venous vessels (> 200
      patients) and hysterosalpingocontrast sonography (> 500 patients).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8267360
TI  - Vascular interventions in the abdomen: current status.
AB  - Vascular and interventional radiology has grown at a remarkable pace due to three
      major factors. Firstly, many disease processes are now amenable to definitive
      diagnosis and management in a less invasive manner, by the radiologist. Secondly,
      most interventional procedures have low and acceptable complication and morbidity
      rates compared to surgery. Additionally, an interventive procedure does not
      preclude the patient from having a surgical procedure, if subsequently deemed
      necessary. Thirdly, the continuing surge and development of new innovative
      technology has provided for increased safety and better results. The advent of
      digital subtraction angiography, small balloon catheters, safe-guide wires,
      expandable stents, new thrombolytic agents and non-ionic contrast media have all
      contributed significantly to the expansion of interventional radiology.

PMID- 8267361
TI  - Prospects for tumour imaging with radiolabelled antibodies.
AB  - An ideal diagnostic imaging method in cancer management should be one which
      surveys the entire body for occult or small tumour foci in a single procedure.
      Imaging with radiolabelled antibodies appears to have such potential if the
      limiting factors which we have encountered in the last 40 years can be completely
      eliminated. These factors include antibody-dependent factors, radionuclide
      dependent factors, host-dependent factors and imaging modality-dependent factors.
      Advances in immunology and bio-genetic engineering have enabled production of
      various antibody fragments and genetically engineered antibody molecules (i.e.
      chimeric/humanized antibodies and the single-chain antigen binding protein),
      giving a promise of overcoming the problem of cross-reactivity and host immuno
      response. The rapid development in radiopharmacy and labelling chemistry has led
      to the establishment of various pre-targetted methods which are aimed to improve
      the tumour to non-tumour ratio. The recent success of producing Tc99m labelled
      monoclonal antibodies preparation in a kit form has certainly encouraged its
      clinical applications and made antibody imaging a less tedious task. The
      progression in computer technology has made "image fusion" possible and hence
      improve the accuracy of anatomical localization of tumour foci in antibody
      imaging. It would appear possible to overcome most, if not all, of the limiting
      factors mentioned above in the near future. The prospect of radiolabelled
      antibodies in tumour imaging is promising and the dream of a "magic bullet" will
      soon be fulfilled.

PMID- 8267362
TI  - Clinical applications of magnetic resonance imaging in the central nervous
      system.
AB  - This review article draws upon the extensive comparative studies between computed
      tomography (CT) and magnetic resonance (MR) imaging in the central nervous
      system. The comparisons and clinical applications of the imaging modalities are
      discussed under specific regions. Whenever possible, actual statistics from the
      comparative studies are cited. The results show a distinct advantage of MR over
      CT in the posterior fossa, the perisellar region and diseases involving the
      leptemeninges and white matter. Cranial nerves, which are usually not seen on CT,
      are much better appreciated on MR imaging. Because of its multiplanar capability,
      lesions adjacent to the skull base are better demonstrated on coronal and
      sagittal planes. CT is able to show calcification, subarachnoid haemorrhage and
      acute haematoma better than MR. In acutely-ill patients with cerebro-vascular
      accident and head trauma, CT is also found to be more useful than MR. This
      article also gives a suggested guideline of the clinical applications of MR as a
      primary or complementary imaging modality.

PMID- 8267363
TI  - Rectal perforation after barium enema in a patient with cytomegalovirus colitis-
      a case report.
AB  - The very rare complication of rectal perforation during the barium enema of an
      immunocompetent Chinese man with cytomegalovirus (CMV) colitis is described.
      Rectal biopsy performed over three weeks earlier was unlikely to have been
      related to the perforation. Histopathological examination of the colonic mucosa
      showed features of active chronic colitis and CMV infection. After treatment with
      Ganciclovir, there was cessation of symptoms with eradication of the virus on
      repeat biopsy samples. It is suggested that presence of CMV colitis predisposed
      to rectal perforation. The clinical presentation, course of disease and response
      to treatment supported the concept of CMV as a primary aetiological agent. This
      complication should be borne in mind when performing barium enemas in patients
      with clinical features of colitis, especially if they are immunocompromised.

PMID- 8267364
TI  - Cholangiocarcinoma complicating ulcerative colitis.
AB  - A case of cholangiocarcinoma complicating ulcerative colitis in a young female
      Chinese is presented. The interval between the diagnosis of ulcerative colitis
      and development of bile duct carcinoma was seven years which is relatively short.
      An irregular stricture of the common bile duct associated with dilatation of the
      biliary tree and distension of the gallbladder were recognised at endoscopic
      retrograde cholangiopancreaticogram (ERCP). The clue to the diagnosis was a
      previous history of chronic diarrhoea. Ulcerative colitis is an uncommon disease
      in the Chinese population. Cholangiocarcinoma is a recognised uncommon
      complication.

PMID- 8267365
TI  - Computed tomographic findings of abdominal tuberculosis--report of five cases.
AB  - Five patients with proven intra-abdominal tuberculosis were examined with
      computed tomography (CT) over a period of one year. This revealed
      hepatosplenomegaly in all five cases. Macroscopic nodules were noted in the liver
      and spleen in three cases. All three cases showed more severe involvement of the
      spleen over the liver. Other features were enlarged (para-aortic, para-caval,
      peripancreatic and mesenteric) nodes, ascites, stellate mesentery and thickened
      bowel wall. Incidental extra-abdominal findings included intrathoracic nodules,
      pleural effusion, pericardial effusion with constrictive pericarditis, bony
      osteomyelitis and psoas abscess. Follow-up CT was performed on four of the five
      cases and showed significant resolution of the above findings. In addition, one
      case showed calcification within a healing splenic nodule. The presence of
      macroscopic nodules detected on CT, especially in the spleen, is an unusual
      finding in prior reports. This paper attempts to account for its high local
      incidence and discusses the significance of other findings in the diagnosis of
      abdominal tuberculosis.

PMID- 8267366
TI  - Familial Behcet's syndrome with intestinal involvement--case reports and a review
      of the literature.
AB  - Behcet's syndrome is a rare multisystem disorder. The occurrence in families
      although well recognised is uncommon. The mode of inheritance, however, has not
      been elucidated. Sixty-one cases of familial disease have been documented to
      date. There was only one previous report on familial Behcet's syndrome with
      gastrointestinal involvement. This paper reports two cases of Behcet's syndrome
      with gastrointestinal involvement in a Malaysian woman of Chinese ethnic origin
      and her child. The mother satisfied three major criteria (oral ulcers, genital
      ulcers and erythema nodosum) and one minor criterion (gastrointestinal
      involvement). Her son satisfied two major criteria (oral and genital ulcers) and
      three minor criteria (intestinal involvement, central nervous manifestation and a
      positive family history). The radiological and pathological features of the
      gastrointestinal lesions in both patients resembled those of Crohn's disease. The
      literature on Behcet's syndrome is reviewed.

PMID- 8267367
TI  - Interventional neuroradiology in the management of paediatric cerebral
      arteriovenous malformations: illustrative study of three case reports.
AB  - Cerebral arteriovenous malformations in children are unusual. Diagnosis and
      management of these lesions may present a problem. As the prognosis of this
      disease in children is worse than in adults, intervention is favoured over
      conservative therapy. Recently, interventional neuroradiology has emerged as an
      effective mode of treatment for these lesions, particularly in the subgroup of
      vein of Galen malformations where conservative and surgical therapies are
      associated with high mortality rates. Three representative cases are discussed to
      illustrate the role of interventional neuroradiology in different clinical
      situations. The first is a young child with a vein of Galen malformation. The
      second is a thirteen-year-old boy with an inoperable deep-seated arteriovenous
      malformation. The last is a twelve-year-old child with an occipital arteriovenous
      malformation. A multi-disciplinary approach to the management of these serious
      lesions is essential in order to achieve the maximum benefit with the lowest
      possible complication rate.

PMID- 8267368
TI  - Pelvic insufficiency fractures in the elderly.
AB  - Insufficiency fractures are a subgroup of stress fractures which occur when
      normal or physiological stresses are placed on weakened bone. Occurrences of
      these fractures in the pelvis are difficult to detect clinically and the
      appropriate radiological investigation is necessary for diagnosis. Osteoporosis
      is the main underlying cause of these fractures. The clinical and radiological
      features of three elderly patients with varying presentations of pelvic
      insufficiency fractures are described. Together with images from three other
      patients, the radiological spectrum of these fractures is illustrated. The
      current literature on this subject is reviewed. Plain radiographs are usually
      unhelpful or may be misleading. Isotope bone scans are the most sensitive
      modality, demonstrating complete or partial H-shaped sacral uptake,
      parasymphyseal uptake, or a combination of both. CT is useful for confirming
      these fractures and excluding malignant disease. Patients invariably improve with
      bed rest. Awareness of this entity should lead to utilisation of the appropriate
      imaging modalities for its diagnosis, the proper patient management and avoidance
      of unnecessary invasive procedures.

PMID- 8267369
TI  - Two case reports of intracranial teratoma diagnosed antenatally.
AB  - Two cases of foetal intracranial teratoma, diagnosed by antenatal ultrasound, are
      described. One is a mature teratoma while the other an immature form. The first
      case presented as epignathus with extracranial extension. Very few cases of fetal
      intracranial teratoma have been reported. These are uniformly fatal. A review of
      reported cases indicates that prenatal intracranial teratoma can be accurately
      diagnosed. Prenatal diagnosis would allow for multidisciplinary team approach and
      planned delivery in a tertiary care centre.

PMID- 8267370
TI  - Development of radiology in Singapore (Part I): 1896-1970.

PMID- 8267371
TI  - History of Singapore radiology (Part II): 1970 to the present.

PMID- 8267372
TI  - Itraconazole and fluconazole in oropharyngeal candidiasis.
AB  - Itraconazole and fluconazole are two relatively new anti-fungal agents which are
      being used successfully in the treatment of oropharyngeal candidiasis. The
      pharmacology of these two drugs and their use in clinical studies are discussed
      in this review.

PMID- 8267373
TI  - Foliate papillitis occurring in a child: a case report.
AB  - Foliate papillae may occasionally become irritated, resulting in an hypertrophy
      of lymphoid tissue. This condition has been described in the literature as
      foliate papillitis and has been reported to occur in adults. We describe here an
      unusual case of foliate papillitis in a 9-year-old girl. Clinically the patient
      presented a pronounced enlargement of one foliate papilla. Furthermore, the
      lesion had a polypoid morphology and the mass appeared microscopically as
      aggregates of lymphoid tissue showing a reactive hyperplasia.

PMID- 8267374
TI  - 20 years of dental employee economics.
AB  - A twenty-year review of the economics of dental practice indicates a relatively
      stable financial picture except for a down-town during the period of the
      recession in the early 1980s. While dental employee economics tend to mirror
      these changes, in the early 1990s general salaries (except for dental hygienists)
      have not maintained parity with the rate of inflation. Potential future shortages
      of dental auxiliaries may require changes in dental employee economics.

PMID- 8267375
TI  - Stickler syndrome: report of four cases.

PMID- 8267376
TI  - Neuropsychiatric disorders and periodontal disease.
AB  - The purpose of this study was to compare the severity of periodontal disease
      among subjects with neuropsychiatric disorders with that of a control group of
      normal subjects in order to determine the association between emotional
      disturbances and periodontal disease. One hundred and sixty-three subjects
      hospitalized for neuropsychiatric conditions (NP) and 78 control subjects with no
      emotional problems were examined. Periodontal attachment loss was measured using
      Russell's index (PI), and the oral hygiene status was evaluated with the Oral
      Hygiene Index (OHI) of Green and Vermillion by a single examiner. Full mouth
      radiographs were also evaluated. The results showed that mean PI, debris,
      calculus, and OHI scores were generally higher in NP subjects compared to
      controls. When the effects of severity of debris, calculus, and OHI scores, and
      daily tooth brushing frequency were controlled, NP subjects had statistically
      significantly higher mean PI scores than controls. These findings suggest that
      emotional problems may be associated with the severity of periodontal disease.

PMID- 8267377
TI  - The treatment of oral lichen planus.
AB  - Lichen planus is a common oral dermatosis and it is one frequently encountered by
      oral surgeons. Lichen planus can be very difficult to treat, particularly when
      symptomatic in its erosive and ulcerated forms. This article describes several
      treatment modalities in the control of oral lichen planus including steroids,
      griseofulvin, vitamin A, cyclosporine, surgical excision, et al. Other features
      included consist of proper biopsy site selection, the need for annual re
      examination, lichen planus's malignant potential, and when "not to treat."

PMID- 8267378
TI  - Erupted compound odontoma.
AB  - A case is described in which a compound odontoma erupted into the oral cavity in
      an 8 1/2-year-old girl. The odontoma was initially discovered as a chance
      radiographic finding 2 years 8 months previously.

PMID- 8267379
TI  - Adoptive immunotherapy of advanced renal cell cancer using PHA-stimulated
      autologous lymphocytes.
AB  - Patients with advanced renal cell carcinoma, previously failed maximal treatment
      with standard chemo-hormonal-radiation therapies, were treated with plant lectin
      phytohemagglutinin (PHA)-stimulated autologous peripheral blood lymphocytes in a
      10-year study with a 16-year follow up period. In a phase I-II setting, 52
      patients were given subcutaneously 40-80 x 10(6) PHA-stimulated lymphocytes
      weekly for 3 weeks and then escalated to a maximum number of 80 x 10(9)
      lymphocytes over the next 9 weeks at 3 week intervals. In vitro blastogenesis
      under study conditions (10 micrograms/ml PHA for 72 hr) measured by [3H]thymidine
      uptake was optimal with lymphocyte stimulating indexes approaching 300.
      Lymphocytes obtained from patients with breast cancer, melanoma and renal cell
      carcinoma responded to PHA similarly to those from normal volunteers. All
      patients that responded developed erythematous reactions at the sites of
      injection; malaise, joint paint and chill-fever for 24-48 hr. The patients that
      responded the best were those with at least 1 positive reaction out of 4 skin
      tests (tuberculosis, yeast, dermatophytin, mumps) prior to therapy. All toxicity
      was transient and did not exceed Grade I based on criteria of the Southwest
      Oncology Group. The majority of patients developed a lymphopenia in the first 24
      hr followed by a lymphocytosis 48-72 hr later. For some patients the
      lymphocytosis was as much as 30% atypical lymphocytes. Of 41 evaluable patients,
      there were 5 complete responses, 8 partial responses, 3 stable diseases, and 25
      progressive disease. The overall response rate was 32% and the median survival
      was 2.8 years.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267380
TI  - p53 mutations in colorectal cancers in the patients of Metropolitan New York.
AB  - An unselected series of 19 colorectal adenocarcinomas obtained from patients
      treated by surgery at Memorial Sloan-Kettering Cancer Center (MSKCC), New York,
      USA was investigated for mutations in exons 5, 6, 7 and 8 of the p53 gene. Ten of
      the tumors revealed at least one somatic mutation either in the exon 5 or 8. Two
      of them were found to carry two somatic mutations each. The DGGE pattern of one
      of these two tumors indicated that it contained two different clonal cell
      populations; a similar assessment was not possible in the other tumor. Sequence
      analysis of all the observed variants showed that eighty percent of the mutations
      were due to transitions and that half of them were at mutational hot spot codons,
      175 and 273.

PMID- 8267381
TI  - Augmentation of lymphokine-activated killer cell activity by lentinan.
AB  - Lymphokine-activated killer (LAK) activity stimulated by interleukin 2 (IL-2)
      and/or lentinan was examined in the peripheral blood of 9 healthy subjects and 7
      cancer patients. After 4 and 8 days culture, LAK killer activity stimulated by IL
      2 and lentinan against autologous tumor and K562 cells was greater than that
      stimulated by IL-2 alone. The optimal concentration of lentinan for the
      generation of killer cells ranged from 25-500 ng/ml, a level which can be
      achieved in vivo by the administration of clinical doses of this agent. The
      expression of CD25 antigen, the alpha chain of the IL-2 receptor on the activated
      killer cells was increased by lentinan. Thus it was shown that LAK cells
      stimulated with IL-2 plus lentinan had strong cytotoxicity and might be useful as
      effector cells for adoptive immunotherapy.

PMID- 8267382
TI  - Palmar-plantar erythrodysestasia syndrome associated with 5-fluorouracil
      treatment.
AB  - Palmar-Plantar Erythrodysestasia Syndrome (PPES) or Hand-Foot Syndrome (H&F S) is
      an underestimated adverse reaction to chemotherapeutic agents, mainly related to
      5-Fluorouracil. From March 1991 to February 1992, at the San Giovanni Oncologic
      Hospital of Torino, we observed 12 out of 163 patients (7.3%) displaying PPES
      while being treated with 5-FU containing regimens. No correlation with type of
      neoplastic disease, sex, age and total dose of administered 5FU was observed.
      Dose reductions or drug suspension achieved PPES reversal. The etiopathogenesis
      remains unclear. Both an idiosyncratic pattern and cutaneous drug accumulation
      are suggested.

PMID- 8267383
TI  - Modulation of lectin-triggered superoxide release from neutrophils of tumor
      patients with and without chemotherapy.
AB  - Superoxide production by neutrophils is believed to contribute to the efficiency
      of the host defence system. This activity is stimulated by the mannose-specific
      lectin concanavalin A, the N-acetylglucosamine/neuraminic acid-specific wheat
      germ agglutinin and the galactoside-specific lectins from Viscum album and human
      placenta. To assess whether this aspect of immune function is affected in cancer
      patients without or with treatment, neutrophil preparations from 69 patients were
      examined. Reductions in O2.(-)-production were observed for bronchial carcinoma
      patients after incubation with concanavalin A and the human lectin, while samples
      from breast cancer patients without or with treatment exhibited no significantly
      altered activity in the presence of each of the four agglutinins. Chemotherapy of
      lung and colorectal carcinoma patients reduced the neutrophilic response to
      concanavalin A and Viscum album agglutinin. As similarly shown for 9 specimens
      from other carcinoma types and from hemopoietic malignancies, there is no general
      impairment of responsiveness. In addition to the property of the lectin, the
      large extent of interindividual variation should be taken into account when it is
      attempted to enhance this factor of the host defence system against infections
      and malignant cells.

PMID- 8267384
TI  - Adenoma follow-up in at-risk Lynch syndrome family members.
AB  - Persons at 50% risk of Lynch Syndrome were screened with colonoscopy at six or
      twelve month intervals. On initial exam, eight of fifty-five patients had
      adenomas. Follow-up was available in 27 patients (mean 35.5 months). Estimated
      time to finding new adenomas was 58 months for patients clear on first
      colonoscopy and 16 months for patients who had adenomas on first exam (p < 0.01).
      One adenocarcinoma has been found, arising in a tubulovillous adenoma. The short
      term risk of colorectal cancer in Lynch syndrome relatives without adenomas is
      low, as is the risk in those who had all adenomas removed.

PMID- 8267385
TI  - Clinical pharmacokinetics and pharmacodynamics of anticancer agents in pediatric
      patients (review).
AB  - The pharmacokinetics of several important anticancer agents used in pediatric
      oncology are reviewed. Many of the anticancer agents described showed age
      dependent pharmacokinetics, the disposition in children being different compared
      to the adult pharmacokinetics. These age-dependent pharmacokinetics imply that it
      is inappropriate to extrapolate pharmacokinetic data from studies in adult
      patients. Interpatient pharmacokinetic variability in pediatric patients was
      large, and of a greater magnitude compared to the variability observed in adult
      patients. This variability in pharmacokinetics resulted in similar large
      variability in systemic exposure after administration of standardized doses (e.g.
      the maximum tolerated dose) of these anticancer agents. The variability of some
      of these agents is correlated with their clinical effects (either tumor response
      or toxicity). It is possible, using these anticancer agents, to monitor pediatric
      patients, identifying those patients at risk of severe toxicity (high systemic
      exposure) or those patients who may not benefit from treatment (Low systemic
      exposure). These pharmacodynamic relationships are described in this paper, since
      such correlations may contribute to further optimization of chemotherapy in
      pediatric patients.

PMID- 8267386
TI  - Effect of krestin (PSK) as adjuvant treatment on the prognosis after radical
      radiotherapy in patients with non-small cell lung cancer.
AB  - From 1976 to 1985, 185 patients with non-small cell lung cancer at stages I-III
      were treated with definitive radiotherapy in Gunma University Hospital. As a
      result of analyzing the long-term survivors treated with radiotherapy, suitable
      conditions of the patients for radical radiotherapy were as follows; 1) stage I
      or II, and some stage III, 2) as regards the histologic type epidermoid carcinoma
      or well-differentiated adenocarcinoma, 3) as regards the primary sites, the upper
      lobe and the superior segment of the lower lobe, 4) the optimum dose was 60-70Gy,
      5) the size of the radiation fields given > 40Gy was 100 cm2 or less, and 6) the
      host condition was satisfactory (BRM combined use). In particular, as a result of
      administering PSK as adjuvant treatment to patients with epidermoid carcinoma of
      the lung showing satisfactory tumour shrinkage after radiotherapy, the five year
      survival rate of the patients with stages I or II disease, as well as stage III
      was 39% and 22% respectively, compared with the non-administered group's 16% and
      5%. These differences are statistically significant. Although an improvement in
      the results of treatment with the combined use of appropriate BRMs is anticipated
      in the future, when clinical trials for combined BRM and radiotherapy are
      planned, the subjects should be patients with satisfactory tumour regression
      after radiotherapy.

PMID- 8267387
TI  - Prediction of individual patient response to chemotherapy by the fluorometric
      microculture cytotoxicity assay (FMCA) using drug specific cut-off limits and a
      Bayesian model.
AB  - The semiautomated fluorometric microculture cytotoxicity assay (FMCA) based on
      the measurement of fluorescence generated from cellular hydrolysis of fluorescein
      diacetate (FDA) to fluorescein in microtiter plates, has been used for
      determination of cytotoxic drug resistance of tumor cells from patients with
      hematological and solid tumors. In the present study we describe a calibration
      procedure based on statistically derived cut-off limits and assay-predicted
      response probabilities using Bayes' theorem. Test results at a specified drug
      concentration were divided into three categories: low, intermediate or extreme
      drug resistance (LDR, IDR and EDR, respectively) using the median and median +1
      standard deviation as the cut-off limits. When correlated with clinical outcome,
      LDR samples showed a higher response rate than expected, IDR a lower and EDR
      samples no response at all. The sensitivity and specificity of the test, using
      the median as cut-off limit, were 0.92 and 0.69 respectively. By fitting these
      test characteristics to a statistical model based on Bayes' theorem it is
      possible to calculate response probabilities for each individual patient taking
      into consideration not only the test characteristics and the particular assay
      result, but also the clinical and patient specific characteristics influencing
      the pre-test probability of response. EDR predicts clinical drug resistance with
      high specificity and is also observed in tumor types with high response rate.

PMID- 8267388
TI  - Intraperitoneal cisplatin during surgery for gastric cancer and peritoneal
      seeding.
AB  - Forty-five patients with gastric cancer having peritoneal seeding but no liver
      metastases received intraperitoneal cisplatin, 50 to 200 mg (89.4 mg on average),
      immediately after gastrectomy, while 37 controls were treated with intravenous
      mitomycin C on the day of their gastrectomy and daily oral tegafur (N1-(2'
      tetrahydrofuryl)-5-fluorouracil) postoperatively. Side effects and postoperative
      complications after intraperitoneal cisplatin were limited. The postoperative
      survival rate was better in patients given cisplatin than in the controls (P <
      0.05). A significant difference in survival was seen particularly in those with
      the undifferentiated type of gastric cancer or 'massive' peritoneal seeding. The
      succinate dehydrogenase inhibition test for chemosensitivity to drugs revealed
      that tissues obtained from the undifferentiated type of gastric cancer or foci of
      peritoneal seeding were more sensitive to cisplatin than to mitomycin C or
      adriamycin. These results demonstrate that intraperitoneal cisplatin after
      gastrectomy is safe and suitable for the treatment of patients with gastric
      cancer and peritoneal seeding.

PMID- 8267389
TI  - Early stage carcinoma of the gastric remnant in Japan.
AB  - In recent years, the number of reported cases of early stage cancer of the
      remnant stomach has been on a gradual increase thanks to the improvement in
      diagnostic techniques and also to increasing dealings with cancer of the remnant
      stomach. In this study we reviewed 124 cases of early stage cancer of the remnant
      stomach which were reported in Japan by the end of 1990, including the 6 cases
      which we encountered ourselves, during the 11 years starting from 1980. Their
      average age was 57 years, with a range from 22 to 78 years. The male-to-female
      ratio was 2:7. There were 63 asymptomatic cases (61%). This fact suggests that
      periodical examinations are essential after the first operation on the stomach.
      Out of the 124 cases, 86 cases operated on for benign lesions (benign group) and
      the remaining 38 cases for malignant lesions (malignant group) for the first
      time. The average time between the first and the second surgery was 19.7 years in
      the benign group and 7.8 years in the malignant group. The initial surgery was
      performed mainly by Billroth II resection. The frequency of tumor development was
      higher in the nonsutured portion than in the anastomosed portion of the remnant
      stomach. Protuberant type lesions and differentiated carcinomas were prevalent
      according to the classification by gross type and histology, respectively.
      However, the anastomosed portion was most often involved in the subgroup of
      patients in whom lesions were detected more than 10 years after Billroth II
      resection for benign lesions.

PMID- 8267390
TI  - Adjuvant portal liver infusion with 5-fluorouracil and mitomycin in colorectal
      cancer. SAKK.
AB  - Between 1981 and 1987, 533 patients from 9 institutions were entered in a
      randomized trial to assess the value of adjuvant perioperative portal infusion
      with Fluorouracil and Mitomycin as compared to radical surgery alone. Analysis of
      469 evaluable patients at a median follow-up of 5.8 years revealed 110
      recurrences in the control and 94 recurrences in the infusion group. Estimated 5
      year disease-free survival was 52% and 61% respectively (hazard ratio: 1:0.75;
      95% confidence interval 0.57-0.99; p = 0.046). Overall survival was 59% in the
      control and 69% in the infusion group (p = 0.048). Adjuvant portal infusion did
      not influence the occurrence of liver metastases but reduced the overall
      recurrence rate.

PMID- 8267391
TI  - Microangiopathic hemolytic anemias (MAHA) in cancer. A case report and review.
AB  - Microangiopathic hemolytic anemia in cancer, MAHA, a rare complication seen in
      connection with malignancies, exists in two forms. One form is associated with a
      disseminated disease and the other with chemotherapy, especially use of mitomycin
      C in patients with limited disease or in patients in clinical remission. Both
      forms give rise to a severe, hemolytic anemia and the latter form also to renal
      insufficiency. MAHA is a life-threatening condition with poor prognosis unless it
      is identified early and treated. The two forms of MAHA are reviewed below and a
      case report is included.

PMID- 8267392
TI  - Cerebral ventricular fluid distribution of subcutaneous granulocyte-macrophage
      colony stimulating factor.
AB  - After treating a child suffering from disseminated primitive neuroectodermal
      tumor and hydrocephalus with bilateral ventriculostomies, we administered
      intravenous high dose thiotepa followed by a single subcutaneous dose of GM-CSF
      24 hours later. The appearance and clearance of GM-CSF were measured from both
      ventricles, one of which was surrounded by tumor. Peak levels of GM-CSF were
      recorded simultaneously in both ventricles 11 hours after injection. Complete
      clearance from injection required 15 hours and 31 hours for the tumor-free right
      ventricle and the tumor-involved left ventricular wall, respectively. Tumor
      response was ephemeral and limited to ventricular fluid WBC, protein and LDH
      decreases. Microglia were detected; however, there was no evidence of anti-tumor
      activity in biopsied tumor tissue. Tumored regions of the brain may have
      perturbation of GM-CSF distribution and clearance which may contribute to the
      lack of microglial activity.

PMID- 8267393
TI  - Chromosomal heterogeneity of aneuploid leukemic cell populations detected by
      conventional karyotyping and by fluorescence in situ hybridization (FISH).
AB  - Beside the frequent aneusomies of chromosomes # 7 and # 8 gains or losses of
      several other chromosomes are found in bone marrow cells of leukemia patients.
      Chromosomal heterogeneity of interphase cell populations was studied by
      fluorescence in situ hybridization (FISH) with centromeric DNA probes for
      chromosomes #2, #3, #4, #6, #9, #11, #12, #15, #16, #17, #18, #20, as well as X
      and Y which were found to be aberrant by routine karyotyping of 28 cases of
      various malignant hematopoietic diseases. Particularly, the data obtained by both
      routes of analysis were compared quantitatively. As the most prominent result,
      all aberrations found by classical karyotyping were redetected by interphase
      cytogenetics, but additional aberrant clones could be observed among the
      interphase cell populations. The frequencies of the cell clones with hypersomies
      were in general higher in metaphase than in interphase, and, vice versa,
      monosomic cells were found more frequently in interphase than in metaphase.
      Single aberrant karyotypes in all cases were redetected as microclones of
      interphase cells. Interphase cytogenetics using FISH, therefore, was shown not
      only to be a reliable measure of the genomic heterogeneity of leukemic cell
      populations but, in addition, to be a valuable and informative supplement to
      routine leukemia cytogenetics with regard to the detection of microclones which,
      later on, could dominate the progression of the malignant disease.

PMID- 8267394
TI  - DNA histogram typing in human seminomas.
AB  - Characterization of the nuclear DNA content (DNA index and DNA histogram type)
      was carried out in 9 normal testicular tissues and 21 seminomas. Proliferative
      activity was further determined in the seminomas. Nuclear DNA content was
      assessed by means of a cell image processor computing the integrated optical
      density on Feulgen-stained nuclei from formalin-fixed paraffin-embedded
      materials. The results indicated that the so-called normal testicular tissues
      exhibited DNA histograms where three cell nuclei populations emerged in varying
      proportions. These three cell nuclei populations corresponded to haploid, diploid
      and tetraploid cell nuclei respectively. In contrast, most of the seminomas
      exhibited monomorphic DNA histogram patterns with a predominance of GO-G1 cell
      nuclei in the range of the 3c-4c nuclear DNA content. Further studies will be
      necessary in order to determine whether the DNA histogram has a predictive
      prognostic value or could be considered as a grading index.

PMID- 8267395
TI  - Preoperative hook-wire localization of nonpalpable breast lesions by use of
      standard and stereotactic technique.
AB  - A series of 151 women underwent 153 preoperative hook-wire localization of
      nonpalpable breast lesions, all of them without reinserting the needle. Measured
      by our criteria, the success for localization procedure was stereotactically 73%
      and conventionally 47%. Measured by criteria of surgeon acceptability and
      evidence of successful removal of the lesion, the success rate for localization
      was stereotactically 84% and conventionally 97%. Failure to remove the suspicious
      lesion in our series was more common after stereotactical than conventional
      localization with larger specimens. At present our experience and results of
      stereotactic wire localization are improving. We believe that the stereotactic
      wire localization without previous checking of the needle position is accurate
      and shortens the time required for the whole procedure.

PMID- 8267396
TI  - Vitamin B12 malabsorption after irradiation for gynaecological tumours.
AB  - The serum vitamin B12 levels were determined in 44 asymptomatic patients at least
      one year after completion of pelvic irradiation for a gynaecological tumour. Ten
      patients (23%) were found to have decreased levels of serum vitamin B12, of which
      six (14%) were assumed to be caused by malabsorption due to radiation damage to
      the terminal ileum as no other reason for a lower vitamin B12 level could be
      detected. Neither the radiation dose or volume nor the manifestation of acute or
      late radiation side effects appeared to be correlated with the finding of
      decreased levels of vitamin B12. It is concluded that even in asymptomatic
      patients who received pelvic irradiation, serum vitamin B12 levels can serve as a
      marker for radiation enteropathy. It is advocated to check vitamin B12 levels
      prior to the radiation treatment as well as during the follow-up of these
      patients.

PMID- 8267397
TI  - Clinical evaluation of tissue polypeptide antigen (TPA) in the diagnosis of
      pancreatic carcinoma.
AB  - The serum values of tissue polypeptide antigen (TPA) were measured in a
      prospective series of 100 patients with jaundice, 54 patients with suspicion of
      chronic pancreatitis or a pancreatic tumour, and 19 patients with unjaundiced
      cholestasis to assess its value in diagnosing pancreatic cancer. There were
      altogether 25 patients with a cancer of the pancreas including 2 patients with a
      cancer of the papilla of Vater. The highest serum TPA values were noticed in
      patients with pancreatic cancer, but raised values were also seen in patients
      with malignant or benign liver diseases, and with cholangiocarcinoma. The
      sensitivity of TPA was 52% with a specificity of 85% and an efficiency of 80%. In
      comparison to CEA, CA 50 and CA 242, TPA showed lower sensitivity but higher
      specificity. When TPA was combined with the other markers, the specificity and
      efficiency improved clearly in all combinations, being highest in that of TPA and
      CA 242 (specificity 94.5%, efficiency 87.2%). The results suggest that the TPA
      test has a useful complementary role in the clinical use of the current serum
      tumour markers in the diagnosis of pancreatic cancer.

PMID- 8267398
TI  - How can treatment response be measured in breast cancer patients?
AB  - Serum TPS, CA 15-3 and CEA levels were measured in 31 women when progressive
      metastatic disease was established according to UICC criteria. A method was
      developed to apply these serum tumor markers in order to measure the short-term
      effect of the treatment. Using strict criteria, whereby an increase of the
      markers of more than 25% indicated progressive disease and a decrease of more
      than 50% indicated a positive effect of the treatment, TPS (which measures
      tumoral activity) was shown to be a more sensitive and earlier marker for
      measuring treatment response than CA 15-3 and CEA (which measure tumor mass).

PMID- 8267399
TI  - Induction of differentiation and growth suppression of myeloid leukemia cells by
      sera of patients with hematological disorders.
AB  - In severe infection, the host responds to foreign agents and produces cytokines
      to activate lymphocytes and macrophages. Some of these cytokines can modulate
      growth and differentiation of myeloid leukemia cells. We examined differentiation
      inducing activities in the sera from 9 patients with leukemia or lymphoma. These
      results indicate that some sera from infected patients, even with acute leukemia,
      have significant differentiation-inducing activities on both mouse and human
      leukemia cells, and that cytokines having differentiation-inducing activities
      varied for different specimens.

PMID- 8267400
TI  - 5q-: pathogenetic importance of the common deleted region and clinical
      consequences of the entire deleted segment.
AB  - Partial deletion of chromosome 5q (5q-) is a frequent aberration in
      myelodysplasias and acute nonlymphocytic leukemias. It causes clinical and
      hematological symptoms termed the 5q-syndrome. Although more than 30 different 5q
      deletions are described, recent studies have demonstrated 5q31 as the common
      deleted region and have mapped a tumor suppressor (IRF-1) and a cluster of
      interleukin genes to 5q31. Furthermore, del(5)(q13q33) is associated with longer
      survival, which means that 5q segments other than 5q31 also are of importance.
      These data suggest that loss of the suppressor releases the malignancy,
      interleukin losses determine the hematology and deletion of other 5q segments
      affect survival.

PMID- 8267401
TI  - Prospective randomized clinical trial of primary treatment in breast cancer
      stages T3/4, N+/-, MO. Chemotherapy vs. radiotherapy. Arbeitskreis fur
      Perioperative Chemotherapie.
AB  - 209 patients entered a randomized trial. We compared a) pre- and postoperative
      chemotherapy (= treatment A) [5-drug combination chemotherapy+tamoxifen] versus
      b) pre- and postoperative radiotherapy (= treatment B). Nonresponders to
      preoperative chemotherapy were << crossed over >> to postoperative radiotherapy.
      The study was started in 1983. We now report on 8 years of results. The reduction
      in tumor size following preoperative treatment was comparable in both legs of the
      study. No differences were seen with regard to the response of patients with
      primary tumors or axillary lymph node involvement. Remission rates for treatments
      A and B were around 60%. In isolated cases the extent of mastectomy could be
      reduced as a result of preoperative treatments (breast conserving surgery was
      done in selected cases). While the initially large tumor size often defied even
      an extended radical operation, the tumor reduction achieved by prior treatment
      permitted the removal of macroscopically visible tumor tissue by radical surgery
      using Rotter's procedure. Relapse-free survival (RFS) and overall survival (OAS)
      on chemotherapy (N = 76) proved to be significantly superior in treatment A
      (chemotherapy) compared to B (radiotherapy) (N = 75) [(p for A:B RFS = 0.018) (p
      for A:B OAS = 0.047)]. RFS for << responders >> to chemotherapy was 65% (N = 47)
      and only 20% (N = 29) for non-responders (p responders vs. non-responder =
      0.005). OAS for responders in group A was 79%, and for non-responders 24% (p =
      0.005). OAS in group B (radiotherapy) was only 25%. (p A:B = 0.047).

PMID- 8267402
TI  - ABO and Rh(D) blood group distribution and their implication for feto-maternal
      incompatibility among the Palestinian population.
AB  - ABO and Rh(D) blood group distribution was evaluated among Palestinian women in
      the southern area of the West Bank and east Jerusalem. Eleven per cent of women
      were Rh(D) negative. The review of the last 12,169 deliveries at Makassed
      Hospital showed that 4.8% of Rh(D)-negative mothers gave birth to Rh(D)-positive
      infants with haemolytic disease of the newborn. Thirty per cent of A or B infants
      born to O Rh(D)-positive mothers had a positive direct antiglobulin test with the
      presence of allo-immune A or B antibody in infant serum. ABO incompatibility was
      a major reason for phototherapy during the 1st week of life. Results and
      possibilities for prevention are discussed.

PMID- 8267403
TI  - Analysis of carbohydrates in glycoproteins by high-performance liquid
      chromatography and high-performance capillary electrophoresis.
AB  - We describe two methods for the analysis of oligosaccharide chains in
      glycoproteins by high-performance liquid chromatography (HPLC) and high
      performance capillary electrophoresis (HPCE). O- and N-glycosidically linked
      oligosaccharides released from glycoproteins can be identified as their
      borohydride-reduced forms by anion-exchange HPLC with pulsed amperometric
      detection. N-Glycosidically linked oligosaccharides can also be analyzed as 2
      aminopyridine derivatives by HPCE in direct zone electrophoresis mode in an
      acidic phosphate buffer and zone electrophoresis mode as borate complexes in an
      alkaline buffer. We also present a convenient procedure for the analysis of the
      constituent monosaccharides of these oligosaccharides chains by HPLC based on
      reversed-phase partition mode as 1-phenyl-3-methyl-5-pyrazolone derivatives.

PMID- 8267404
TI  - Cellulase Ss (CelS) is synonymous with the major cellobiohydrolase (subunit S8)
      from the cellulosome of Clostridium thermocellum.
AB  - The controversy regarding the identity of a major cellulosomal component type
      from two different strains of Clostridium thermocellum has been resolved. The
      principal cellobiohydrolase, subunit S8, from the cellulosome of strain YS has
      been demonstrated to be synonymous with cellulase component Ss (CelS) from the
      cellulosome of ATCC strain 27405. This component is not related to any other
      cellulosomal subunit or cloned endoglucanase in this organism.

PMID- 8267406
TI  - Nursing's role in health care reform.

PMID- 8267405
TI  - Glucose and glutamine metabolism of a murine B-lymphocyte hybridoma grown in
      batch culture.
AB  - The energy metabolism of a mammalian cell line grown in vitro was analyzed by
      substrate consumption rates and metabolic flux measurements. The data allowed the
      determination of the relative importance of the pathways of glucose and glutamine
      metabolism to the energy requirements of the cell. Changes in the substrate
      concentrations during culture contributed to the changing catalytic activities of
      key enzymes, which were determined. 1. A murine B-lymphocyte hybridoma (PQXB1/2)
      was grown in batch culture to a maximum cell density of 1-2 x 10(6) cells/mL in 3
      4 d. The intracellular protein content showed a maximum value during the
      exponential growth phase of 0.55 mg/10(6) cells. Glutamine was completely
      depleted, but glucose only partially depleted to 50% of its original
      concentration when the cells reached a stationary phase following exponential
      growth. 2. The specific rates of glutamine and glucose utilization varied during
      culture and showed maximal values at the midexponential phase of 2.4
      nmol/min/10(6) cells and 4.3 nmol/min/10(6) cells, respectively. 3. A high
      proportion of glucose (96%) was metabolized by glycolysis, but only limited
      amounts by the pentose phosphate pathway (3.3%) and TCA cycle (0.21%). 4. The
      maximum catalytic activity of hexokinase approximates to the measured flux of
      glycolysis and is suggested as a rate-limiting step. In the stationary phase, the
      hexokinase activity reduced to 11% of its original value and may explain the
      reduced glucose utilization at this stage. 5. The maximal activities of two TCA
      cycle enzymes were well above the measured metabolic flux and are unlikely to
      pose regulatory barriers. However, the activity of pyruvate dehydrogenase was
      undetectable by spectrophotometric assay and explains the low level of flux of
      glycolytic metabolites into the TCA cycle. 6. A significant proportion of the
      glutamine (36%) utilized by the cells was completely oxidized to CO2. 7. The
      measured rate of glutamine transport into the cells approximated to the metabolic
      flux and is suggested as a rate-limiting step. 8. Glutamine metabolism is likely
      to occur via glutaminase and amino transaminase, which have significantly higher
      activities than glutamate dehydrogenase. 9. The calculated potential ATP
      production suggests that, overall, glutamine is the major contributor of cellular
      energy. However, at the midexponential phase, the energy contribution from the
      catabolism of the two substrates was finely balanced--glutamine (55%) and glucose
      (45%).

PMID- 8267407
TI  - Development of an instrument to measure knowledge about kidney function, kidney
      failure, and treatment options.
AB  - The purpose of this article is to report the development of a valid and reliable
      instrument to measure knowledge in adults with decreased kidney function. The
      Chambers Kidney Knowledge Test (CKKT) will assist nurses and other nephrology
      health care providers to identify learning needs and individualize their
      instructional efforts with predialysis and dialysis patients.

PMID- 8267408
TI  - Current perspectives: iron management during therapy with recombinant human
      erythropoietin.
AB  - Recombinant human erythropoietin (rHuEpo) has been associated with clinical and
      symptomatic improvements as well as improvements in quality of life in patients
      with anemia of chronic renal failure. However, resistance to rHuEpo therapy,
      related to insufficient iron stores, occurs often. Although many patients treated
      with rHuEpo take oral iron, patients continue to develop iron deficiency.
      Parenteral iron is a safe and effective alternative in replacing iron stores to
      sustain erythropoiesis in patients treated with rHuEpo.

PMID- 8267409
TI  - The impact of home dialysis on the family: literature review.
AB  - This critique of 48 research and anecdotal reports published since 1967
      summarizes current understanding about the effects on family members assisting
      with home dialysis. Psychological perspectives have provided descriptions of how
      these family assistants cope with the stresses associated with dialysis. However,
      important societal, gender, and economic factors affecting people with end stage
      renal disease (ESRD) and their families have been overlooked. More comprehensive
      perspectives would illuminate the range of effects home dialysis has on "the
      family"--especially female assistants.

PMID- 8267410
TI  - Psychosocial issues in kidney-transplanted children and adolescents: literature
      review.
AB  - A selective review of the literature on psychosocial issues in kidney
      transplanted children and adolescents was conducted. Treatment programs and
      research studies dealing with the emotional and social adaptation of children
      following kidney transplantation have become increasingly common. The literature
      is largely descriptive. More research building on the findings of these
      descriptions is critical. Possible opportunities for continued study with
      adolescents following kidney transplantation are given.

PMID- 8267411
TI  - Intradialytic parenteral nutrition: a practical approach.
AB  - Intradialytic parenteral nutrition (IDPN) therapy is becoming more prevalent in
      the malnourished patient undergoing maintenance hemodialysis. This is of
      particular concern to the nephrology nurse in that additional time is required to
      administer the solution, monitor the patient, and document the process. The IDPN
      monitoring flowsheet described in this article was developed to promote
      continuity of care from treatment to treatment, especially during initiation of
      IDPN, and to assist the nephrology nurse in administering and monitoring the
      therapy.

PMID- 8267412
TI  - Case management of the anemic patient: epoetin alfa--focus on iron
      supplementation.
AB  - Epoetin alfa stimulates erythropoiesis, thus creating an increased need for iron,
      and virtually all patients with end-stage renal disease who receive this therapy
      will eventually require iron supplementation. This article describes the
      appropriate use of oral and intravenous iron supplementation, including patient
      assessment, education, and management.

PMID- 8267413
TI  - Annotated bibliography: the research question and sample.

PMID- 8267414
TI  - HIV nephropathy management with peritoneal dialysis.

PMID- 8267415
TI  - Meeting nurse practice standards in your state.

PMID- 8267416
TI  - IGIV prophylaxis therapy for CMV in renal transplant recipients.

PMID- 8267417
TI  - CCETS Basic Science Lecture. Transplantation tolerance.
AB  - Two major factors currently limiting the field of transplantation are (1)
      treatment-related complications and (2) donor organ availability. This article
      reviews progress from our laboratory in research directed at solutions to both of
      these limitations. The induction of specific tolerance could eliminate many of
      the treatment-related complications currently attributable to nonspecific
      immunosuppressive drug therapy. The methodology being investigated involves use
      of mixed chimerism as an approach to transplantation tolerance. In this case, the
      presence of certain donor bone marrow-derived elements induces specific
      tolerance, whereas host-type antigen presenting cells confer normal
      immunocompetence. In addition, extension of this work toward tolerance across
      xenogeneic barriers could eliminate the limitation of organ donor availability. A
      nonmyeloablative preparative regimen capable of inducing mixed chimerism and
      tolerance has previously been described from our laboratory for both allogeneic
      murine systems and concordant xenogeneic rat-->mouse systems. Current studies
      attempting to extend this regimen to a discordant pig-->monkey xenograft model
      are reviewed. If successful, these studies could provide a virtually limitless
      source of xenogeneic donor organs.

PMID- 8267418
TI  - Revascularization for acute regional infarct: superior protection with warm blood
      cardioplegia.
AB  - Continuous retrograde warm blood cardioplegia was compared with two widely used
      hypothermic myocardial protection techniques in a canine model of acute regional
      myocardial ischemia with subsequent revascularization. Animals (n = 30) underwent
      45 minutes of left anterior descending coronary artery occlusion then
      cardioplegic arrest (60 minutes), followed by separation from cardiopulmonary
      bypass and data collection. The cold oxygenated crystalloid cardioplegia group
      (CC; n = 8) and the cold blood cardioplegia group (CC; n = 10) had
      cardiopulmonary bypass at 28 degrees C, antegrade arrest, and intermittent
      retrograde delivery. The warm blood cardioplegia group (WB; n = 12) had
      normothermic cardiopulmonary bypass, antegrade arrest, and continuous retrograde
      delivery. Overall ventricular function (preload recruitable stroke work
      relationship; ergs x 10(3)/mL) was significantly (p < 0.001) better for WB (WB,
      80 +/- 11; CB, 67 +/- 13; CC, 57 +/- 12). Systolic function (maximum elastance
      relationship; mm Hg/mL) was also significantly (p < 0.001) better for WB (WB,
      11.6 +/- 3.6; CB, 8.6 +/- 2.7; CC, 6.2 +/- 1.3). Diastolic function (stress
      strain relationship; dynes x 10(3)/cm2) revealed significantly (p < 0.001)
      decreased compliance for CC (WB, 20 +/- 6; CB, 19 +/- 7; CC, 27 +/- 11). Left
      anterior descending coronary artery regional adenosine triphosphate/adenosine
      diphosphate ratios were significantly (p = 0.02) worse for CC (WB, 10.2 +/- 2.3;
      CB, 9.4 +/- 2.6; CC, 5.6 +/- 1.5). Myocardial edema significantly (p = 0.03)
      increased over time only in the CC animals (WB, 0.4% +/- 2.3%; CB, -0.3% +/-
      3.6%; CC, 5.5% +/- 2.3%). In this model of acute regional myocardial ischemia and
      revascularization, continuous retrograde warm aerobic blood cardioplegia provided
      superior myocardial protection compared with cold oxygenated crystalloid
      cardioplegia with intermediate results for cold blood cardioplegia.

PMID- 8267419
TI  - Pediatric cardiac transplantation for congenital heart defects: surgical
      considerations and results.
AB  - Among 54 children who underwent 55 heart transplantations, 24 (44%) (mean age,
      4.9 +/- 4.8 years; range, 9 days to 18 years) had congenital defects with the
      following diagnoses: single-ventricle variants (6), hypoplastic left heart
      syndrome variants (5), transposition complex (6), and miscellaneous defects (7).
      Twenty patients (83%) had undergone 43 prior operations. Additional surgical
      procedures included repositioning of transposed great arteries (11),
      reconstruction of the aortic pathway (4), reconstruction of the pulmonary pathway
      (8), correction of situs inversus (1), and correction of anomalous pulmonary (1)
      or systemic (1) venous drainage. Reconstructive procedures were performed using
      donor or recipient tissue or both. There were six early deaths (hyperacute
      rejection, 1 patient; pulmonary hypertension, 1; graft failure, 2 patients;
      infection, 2) and six late deaths (sudden death, 2; chronic rejection, 2;
      nonspecific graft dysfunction, 1; lymphoproliferative disease, 1). The survival
      rate was 43% +/- 12% at 3 years. No deaths were related to surgical technique.
      Survival was not significantly different in pediatric recipients with
      cardiomyopathy (67% +/- 9%; p = 0.22). Accelerated coronary artery disease was
      noted in 4 operative survivors (22%; 70% confidence limits, 12% to 36%). All late
      survivors were free from cardiac symptoms after a mean follow-up of 34 +/- 24
      months (range, 6 to 71 months). Based on this study, we reached three
      conclusions. (1) Careful planning of both harvesting and transplantation
      procedures allows heart transplantation in recipients with congenital heart
      diseases. (2) The surgical technique may be demanding, but the early risk is not
      increased.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267420
TI  - Initial experience with video-assisted thoracoscopic lobectomy.
AB  - In the past 2 years, the development of video-assisted thoracic surgery (VATS)
      has allowed thoracoscopy to rapidly evolve from a primarily diagnostic tool to a
      therapeutic tool with potentially useful applications. As with laparoscopy, the
      initial enthusiasm for VATS must be tempered by the reality of technical
      inadequacies, complications, and results that have yet to withstand careful
      scientific scrutiny. The purpose of this study was to determine the technical
      feasibility of a VATS lobectomy. Forty-four patients with primary bronchogenic
      carcinoma were evaluated and accepted as potential candidates for VATS lobectomy.
      After complete preoperative staging, these patients were in clinical stage I. All
      patients had normal arterial blood gases and adequate pulmonary function (forced
      expiratory volume in 1 second > 1.5 L) to tolerate a lobectomy. At the time of
      operation, 3 patients were found to have N2 disease and were excluded from the
      study. In 35 of the remaining 41 patients, a successful VATS lobectomy was
      accomplished through two thoracoscopy ports and a non-rib-spreading 6- to 8-cm
      "access" thoracotomy. There were no major intraoperative complications that
      necessitated conversion to an open thoracotomy. Mean operative time was 153 +/-
      26 minutes. All 35 patients recovered uneventfully with a mean hospital stay of
      5.7 +/- 1.6 days. A VATS lobectomy is technically feasible using our approach and
      is potentially safe. However, major advances in thoracoscopy imaging and
      instrumentation are necessary before this procedure will have the potential for
      widespread acceptance. Also, the advantages of VATS lobectomy over accepted
      surgical techniques will have to be carefully documented in randomized trials.

PMID- 8267421
TI  - Comparison of balloon valvuloplasty with operative treatment for mitral stenosis.
AB  - To determine the optimal role for percutaneous balloon mitral valvuloplasty or
      open mitral commissurotomy, the outcome of 164 consecutive patients undergoing
      either percutaneous balloon mitral valvuloplasty, open mitral commissurotomy, or
      mitral valve replacement for mitral stenosis was reviewed. No preoperative
      differences existed between percutaneous balloon mitral valvuloplasty and open
      mitral commissurotomy in age, symptoms, or mitral valve characteristics. Symptoms
      improved similarly in all groups, and median hospital stays after procedures were
      2, 9, and 10 days for percutaneous balloon mitral valvuloplasty, open mitral
      commissurotomy, and mitral valve replacement (p < 0.005). Actuarial survivals at
      36 months did not differ significantly (83% +/- 6%, 94% +/- 4%, and 90% +/- 4%).
      Actuarial freedoms from subsequent mitral valve procedures at 36 months were 66%
      +/- 7%, 87% +/- 6%, and 100% +/- 13% (p < 0.005), with the linearized rate of
      subsequent mitral valve procedures being 12% +/- 3%, 4% +/- 2%, and 1.2% +/-
      0.8%/patient-year for percutaneous balloon mitral valvuloplasty, open mitral
      commissurotomy, and mitral valve replacement (p < 0.01). Prior mitral
      commissurotomy increased the likelihood of subsequent mitral procedures after
      percutaneous balloon mitral valvuloplasty from 10% +/- 3% to 20% +/- 7%/patient
      year.

PMID- 8267422
TI  - Hemodynamic advantage of left atrial epinephrine administration after cardiac
      operations.
AB  - Cardiac surgical patients frequently require catecholamines, typically
      administered via the central venous circulation. Potential disadvantages of this
      route of administration include catecholamine metabolism by the pulmonary
      vascular bed before gaining access to the heart and pulmonary vasoconstriction
      producing increased pulmonary vascular resistance. We therefore prospectively
      compared administration of epinephrine via the left atrium versus central venous
      administration of epinephrine with particular interest in cardiac output, mean
      pulmonary artery pressure, and pulmonary vascular resistance. Fifteen consecutive
      aortocoronary bypass patients were studied after cardiopulmonary bypass.
      Epinephrine (mean dose, 0.07 +/- 0.02 micrograms.kg-1.min-1) was administered via
      the central venous route, then via the left atrium, then via the central venous
      route again. Hemodynamic data were collected 10 minutes after changing the route
      of administration. Left atrial administration of epinephrine produced a 35%
      greater cardiac output, 25% lower pulmonary artery pressure, and 32% lower
      pulmonary vascular resistance when compared with central venous administration
      (all significant; p < 0.05). Left atrial epinephrine administration may offer
      hemodynamic advantage in cardiac surgical patients in whom central venous
      administration does not produce an adequate cardiac output or in patients with
      pulmonary hypertension to avoid any further increase in pulmonary vascular
      resistance.

PMID- 8267423
TI  - Cytomegalovirus disease after heart transplantation: is acyclovir prophylaxis
      indicated?
AB  - To determine the efficacy of acyclovir prophylaxis in preventing cytomegalovirus
      (CMV) disease after heart transplantation, the clinical course of 103 patients
      (ages, 0.1 to 62 years; mean age, 41.8 years; 87 males, 16 females) was analyzed.
      Active CMV infection (defined as a positive culture from any site or a fourfold
      increase in immunoglobulin G antibody titers) occurred in 64% (66/103) and
      clinical CMV disease (defined as pathologic evidence of CMV in tissue biopsy or a
      typical CMV syndrome with fever and two of the following: leukopenia,
      thrombocytopenia, atypical lymphocytes, and elevated liver function test results
      in a patient with CMV infection) occurred in 25% (26/103). Independent variables
      studied included acyclovir prophylaxis, duration of acyclovir use, duration and
      type of induction therapy, donor and recipient CMV status, total steroid dose at
      3 and 6 months, azathioprine dose and cyclosporine level at 3 months, age, and
      sex. In a multivariate regression analysis, acyclovir prophylaxis was
      independently associated with freedom from CMV disease (p = 0.029). Positive
      donor CMV status (p = 0.025), higher total steroid dose at 3 months (p = 0.036),
      and lower azathioprine dose at 3 months (p = 0.047) were associated with higher
      occurrence of CMV disease. The use of antilymphocyte induction therapy was
      associated with an increased occurrence of active CMV infection (p = 0.022) but
      not CMV disease. The prophylactic administration of acyclovir reduced the
      occurrence of CMV disease after heart transplantation.

PMID- 8267424
TI  - Growth potential of the transplanted lung in the infant primate.
AB  - Success in neonatal lung transplantation depends on the growth of the
      transplanted lung. To study the effects of transplantation and denervation on
      primate lung growth without rejection or immunosuppression, an autotransplant
      model was chosen. Eight-week-old baboons underwent left lung autotransplantation
      (n = 5) or sham operation (n = 1). At age 13 weeks and 9 months, single lung
      volumes were calculated by nitrogen washout and computed tomography. Results were
      compared with those of 4 unoperated weight-matched controls (2 per age group).
      Over the growth period, mean total lung capacity in operated baboons increased
      82% (137 to 249 mL) by nitrogen washout and 70% (182 to 309 mL) by computed
      tomography compared with 85% (128 to 237 mL) and 74% (141 to 245 mL) for the sham
      operated baboon, respectively. Transplanted left lung volume increased 91% (53 to
      101 mL) by nitrogen washout and 75% (68 to 119 mL) by computed tomography
      compared with 85% (54 to 100 mL) and 80% (56 to 101 mL) for the sham-operated
      baboon, respectively. In the absence of rejection and immunosuppression, normal
      volume growth occurs in the transplanted infant primate lung.

PMID- 8267425
TI  - Reduction of conjugated dienes in lung transplantation: effect of BN 52021.
AB  - Oxygen-derived free radicals have been identified as the mediators of tissue
      injury during reperfusion in organ transplantation. Lipid peroxidation of cell
      membrane polyunsaturated fatty acids, generating conjugated dienes (CD), is a
      toxicity of oxygen-derived free radicals. The CD structure in fatty acyl moieties
      was measured by high-pressure liquid chromatography in samples of inferior
      pulmonary venous blood and pulmonary tissue to assess reperfusion injury and
      oxygen-derived free radical-mediated damage in a canine model of left lung
      allotransplantation. The cold ischemic preservation interval was 6 hours and the
      posttransplantation monitoring period was 6 hours. Twenty-eight size- and weight
      matched adult male dogs underwent left lung allotransplantation and were
      randomized to receive pulmonary artery flush of modified Euro-Collins (EC) (40
      mL/kg) or University of Wisconsin (UW) (40 mL/kg) solutions alone or with the
      addition of the platelet-activating factor antagonist BN 52021 (10 mg/kg). When
      employed, BN 52021 was administered to donors 30 minutes before harvest and
      recipients 30 minutes before reperfusion. Left and right inferior pulmonary
      venous blood samples were obtained at baseline before transplantation and at 1,
      2, 4, and 6 hours after transplantation; tissue samples were obtained after
      euthanasia. Serum and tissue CD levels are expressed as mean fraction of the
      total hydroperoxide sample +/- standard error of the mean. At 6 hours after
      transplantation, the EC group's (n = 7) CD fraction was 0.28 +/- 0.03, whereas
      that of the EC + BN 52021 group (n = 7) was 0.12 +/- 0.03 (p < 0.05).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8267426
TI  - Postoperative pain-related morbidity: video-assisted thoracic surgery versus
      thoracotomy.
AB  - One hundred thirty-eight consecutive, nonrandomized patients, with equivalent
      demographic and preoperative physiologic parameters, underwent either a video
      assisted thoracic surgical (VATS) approach (n = 81) or a limited lateral
      thoracotomy (LLT) approach (n = 57) to accomplish pulmonary resection for
      peripheral lung lesions (< or = 3 cm in diameter). Wedge resection was done in 74
      VATS patients and 19 LLT patients. Seven patients underwent VATS lobectomy and 38
      patients had lobectomy performed through an LLT. Pain was quantitated by
      postoperative narcotic requirements, the need for intercostal/epidural analgesia,
      and patient perception of pain index scoring. Shoulder and pulmonary function
      (forced expiratory volume in 1 second) were measured preoperatively, 3 days
      postoperatively, and at 3 weeks of follow-up. Patients undergoing VATS
      experienced significantly less postoperative pain. No patients undergoing VATS
      required intercostal block/epidural analgesia; 31 LLT patients (54%) required
      this treatment for breakthrough pain (p = 0.001). Narcotic requirements were less
      (p = 0.05) among VATS patients, which correlated with lower perception of pain
      index after operation for VATS patients. Shoulder girdle strength was equally
      impaired at day 3, but function was more improved in VATS patients at 3 weeks (p
      = 0.01). Patients undergoing wedge resection alone by LLT had greater impairment
      in early (day 3) pulmonary function (forced expiratory volume in 1 second) (p =
      0.002); this difference from VATS was not sustained at 3 weeks. Video-assisted
      thoracic surgery is associated with reduced pain, shoulder dysfunction, and early
      pulmonary impairment compared with LLT for select patients requiring pulmonary
      resection.

PMID- 8267427
TI  - Right latissimus dorsi cardiomyoplasty augments left ventricular systolic
      performance.
AB  - We hypothesized that the right latissimus dorsi cardiomyoplasty augments left
      ventricular performance. Five dogs underwent staged right latissimus dorsi
      cardiomyoplasty. Ventricular function was studied 1 to 3 weeks later. Left
      ventricular pressure was measured with a micromanometer and left ventricular
      dimensions with piezoelectric crystals. Inferior vena caval occlusion was used to
      vary preload. Pressure-volume data were collected with the muscle unstimulated
      and stimulated at 1:2 and 1:1 muscle/heart ratios. The end-systolic pressure
      volume relation (mm Hg/mL), stroke work, preload recruitable stroke work, left
      ventricular end-diastolic volume, and the diastolic relaxation constant were
      calculated and expressed as mean +/- standard deviation. Stimulated beats at a
      1:2 ratio showed an increase in stroke work of 42.1% (978 +/- 381 to 1,390 +/-
      449 g.cm; p < 0.01) and preload recruitable stroke work of 28.8% (59.4 +/- 20.7
      to 76.6 +/- 11.0 g.cm/cm3; p = 0.05) compared with the unstimulated beats. With
      the stimulator on at 1:1, smaller changes occurred: stroke work increased 9%
      (1,167 +/- 390 to 1,273 +/- 363 g.cm; not significant) and preload recruitable
      stroke work increased 27% (63.9 +/- 22.7 to 80.9 +/- 23.1 g.cm/cm3; p = 0.05).
      There were no significant changes in the end-systolic pressure-volume relation.
      The diastolic relaxation constant did not change at 1:1 (36 +/- 9.7 to 37 +/- 6.4
      ms; not significant) or 1:2 (36 +/- 9.3 to 39 +/- 8.2 ms; not significant). Left
      ventricular end-diastolic volume was unchanged at 1:1 (34 +/- 10.7 to 32 +/- 10.3
      mL) and at 1:2 (31 +/- 9.0 to 32 +/- 8.7 mL).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267428
TI  - Factors predictive of operative mortality among coronary artery bypass subsets.
AB  - As risk-adjusted outcome is increasingly being used to make clinical decisions
      and to assess and improve quality of care, it is important to develop simple,
      stable models for predicting outcome. Here we address the hypothesis that a risk
      factor for increased operative mortality at coronary artery bypass grafting may
      have differential effects in subgroups of patients defined by the presence or
      absence of other risk variables. We used a series of univariate and multivariate
      analyses to identify a group of ten patient-related preoperative characteristics
      independently predictive of operative death in the total population of 12,712
      patients undergoing coronary artery bypass grafting at 43 Department of Veterans
      Affairs medical centers participating in the Department of Veterans Affairs
      Continuous Improvement in Cardiac Surgery Study. Separate logistic regression
      models were then developed for each of 14 clinically important subgroups defined
      by the presence or absence of seven risk variables. Odds ratios for operative
      death and estimated operative mortality were calculated from these subgroup
      regression models. Of 65 comparisons of pairs odds ratios of preoperative risk
      variables between the subgroups with and without a second risk variable, only
      five were found to be significant (p < 0.05 without adjustment for multiple
      comparisons); this is only slightly more than would be expected by chance alone.
      Risk factors for increased operative death appear to have similar odds ratios for
      subgroups of patients defined by a second risk variable. This finding greatly
      simplifies the use of predicted operative mortality in clinical decision making
      and quality assessment and improvement in coronary artery bypass grafting.

PMID- 8267429
TI  - Operative treatment of pediatric obstructive hypertrophic cardiomyopathy: a 26
      year experience.
AB  - We retrospectively reviewed the 26-year National Institutes of Health experience
      with operative treatment of obstructive hypertrophic cardiomyopathy in pediatric
      patients. Operative criteria were either severe obstructive symptoms (New York
      Heart Association functional class III or IV) or sudden death. Seventeen patients
      underwent 19 open procedures, of which the present study is comprised. Complete
      follow-up was available 10.1 +/- 1.4 years (mean +/- standard error; range, 0.8
      to 26.2 years) after operation. The mean ages at diagnosis and operation were
      11.9 +/- 1.3 years (range, 1 to 17 years) and 14.8 +/- 0.7 years (range, 9 to 17
      years), respectively. The preoperative intraventricular septum mean dimension was
      23.2 +/- 1.3 mm (range, 11 to 36 mm). The left ventricular outflow tract gradient
      was 74 +/- 9 mm Hg (range, 20 to 175 mm Hg) at rest and 94 +/- 7 mm Hg (range, 55
      to 175 mm Hg) with provocation. Fifteen patients (88%) underwent left ventricular
      myotomy and myectomy, and 2 underwent mitral valve replacement. Two patients who
      initially received left ventricular myotomy and myectomy later underwent mitral
      valve replacement. There were one perioperative death (6%) and five late sudden
      deaths (31%) at 3.8, 8.7, 9.6, 14.1, and 21 years postoperatively. Kaplan-Meier
      survival was 86% +/- 8% at 5 years and 77% +/- 12% at 10 years. After operation,
      the left ventricular outflow tract gradient decreased almost 80% to 21 +/- 15 mm
      Hg (p = 0.0001). In 8 patients, the left ventricular outflow tract gradient
      completely resolved.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267430
TI  - Myocardial function in early hours after coronary artery bypass grafting:
      comparison of two cardioplegic methods.
AB  - The theoretical advantages of retrograde blood cardioplegia combined with
      anterograde blood cardioplegia and warm reperfusion before aortic unclamping
      during coronary surgery were evaluated in 41 patients (group 2). The early
      postoperative myocardial function of this group was compared with that of 55
      patients (group 1) in whom cold crystalloid cardioplegia was administered. The
      following variables were measured and analyzed by multivariate statistical
      analysis: heart rate, left atrial pressure, systemic arterial pressure, cardiac
      index, left ventricular stroke work index, ventricular function, oxygen delivery,
      hemoglobin, partial oxygen pressure in mixed venous blood, arteriovenous oxygen
      difference, carbon dioxide production per square meter, and cardiac isoenzyme of
      creatine-kinase. The myocardial function improved progressively and cardiac
      enzymatic release was low for both groups 9 hours after admission to the
      intensive care unit. However, group 2 had significantly higher oxygen delivery,
      carbon dioxide production per square meter, cardiac index, left ventricular
      stroke work index, and ventricular function and significantly lower left atrial
      pressure and mean systemic arterial pressure than that of group 1. The best
      separation of group 2 from group 1 occurred at the ninth hour, with a probability
      of correct recognition of 92.1%.

PMID- 8267431
TI  - Indications for an expandable metallic stent for tracheobronchial stenosis.
AB  - An expandable metallic stent was used in 9 patients with tracheobronchial
      stenosis. Of the 8 patients with malignant stenosis, 6 had extrinsic compression
      and 2 had intraluminal tumor invasion. The 1 patient with nonmalignant stenosis
      had postreconstruction bronchomalacia and granulation tissue affecting different
      parts of the tracheobronchial tree. The expandable metallic stent successfully
      dilated tracheobronchial stenosis due to extrinsic tumor compression and malacia.
      However, it was not effective for stenosis due to intraluminal tumor invasion or
      granulation tissue because of the growth of tumor or granulation tissue between
      the wires of the stent. However, an expandable metallic stent covered with Dacron
      mesh was effective in 1 patient with intraluminal tumor invasion because tumor
      growth was blocked by the mesh. We conclude that an expandable metallic stent is
      effective for tracheobronchial stenosis due to extrinsic tumor compression, but
      not for stenosis due to intraluminal tumor invasion or granulation tissue.

PMID- 8267432
TI  - Endothelium-dependent relaxation in pulmonary arteries after lung preservation
      and transplantation.
AB  - Pulmonary hypertension is frequently seen after lung transplantation. To study
      how the release of the endothelium-dependent relaxing factor is affected by lung
      preservation and transplantation, porcine pulmonary arteries were investigated in
      organ baths. The arteries (1 mm in diameter) were taken from fresh nonperfused
      lungs (group I), lungs immediately after flush-perfusion with a low-potassium
      dextran solution (group II), non-perfused lungs stored for 12 hours in low
      potassium-dextran solution (group III), flush-perfused lungs stored for 12 hours
      in low-potassium-dextran solution (group IV), and group IV lungs after left lung
      transplantation and right pneumonectomy followed by 24 hours of reperfusion
      (group V). Stable contractions were induced with the thromboxane A2 analogue U
      46619. Acetylcholine was used to stimulate the release of endothelium-dependent
      relaxing factor. In vessel segments where the endothelium had been removed,
      acetylcholine elicited no response. In segments with intact endothelium,
      acetylcholine induced concentration-dependent relaxation; the maximum relaxation
      obtained was 91% +/- 3% (I), 86% +/- 3% (II), 85% +/- 3% (III), 69% +/- 5% (IV),
      and 69% +/- 9% (V). Relaxation was significantly reduced in groups IV (p < 0.01)
      and V (p < 0.05) as compared with group I. Stable moderate pulmonary hypertension
      was present in all the transplanted lungs throughout the 24-hour observation
      period. It is concluded that the endothelium-mediated relaxation is significantly
      reduced after flush perfusion combined with 12 hours of storage in low-potassium
      dextran solution. Lung transplantation, followed by 24 hours of reperfusion did
      not further impair the endothelium-dependent relaxation.

PMID- 8267433
TI  - Phosphatidylcholine-coated chest tubes improve drainage after open heart
      operation.
AB  - Occlusion of chest drainage tubes by thrombus is not uncommon after open heart
      operations. It has been suggested that by coating the tube with
      phosphatidylcholine (PC), the most prominent phospholipid in the erythrocytes
      outer membrane, it may be possible to overcome the blood-material interaction
      responsible for thrombus formation. To test this hypothesis 102 patients (75
      males; mean age, 57 +/- 10 years) were randomly allocated to receive either PC
      coated or noncoated 32F chest drainage tubes. Preoperative status, type and
      length of operation, and duration of drainage were similar in the two groups as
      was postoperative blood loss. Patients receiving PC-coated tubes, however, had
      less residual blood clot in the tube after removal (0.7 +/- 0.1 versus 3.1 +/-
      0.3 g; p < 0.001), a reduced incidence of pericardial effusions (17.6% versus
      41.2%; p < 0.01), fewer postoperative supraventricular arrhythmias (2 of 51
      versus 10 of 51; p < 0.002), and a shorter hospital stay (8.4 +/- 0.3 versus 9.7
      +/- 0.5 days; p < 0.05). Late cardiac tamponade developed in 2 patients in the
      noncoated group 6 and 10 days postoperatively, which required reexploration. The
      data show that PC-coated chest drainage tubes are less susceptible to occlusion
      by thrombus and their use is associated with a significant reduction in
      postoperative morbidity.

PMID- 8267434
TI  - Treatment of peripheral bronchopleural fistulas with endobronchial occlusion
      coils.
AB  - Persistent peripheral bronchopleural fistulas can be difficult to manage.
      Endoscopic plugging of involved bronchi has been accomplished in a number of
      ways. We have devised a method of permanently blocking small peripheral airways
      using Gianturco vascular occlusion coils placed endobronchially by modified
      angiographic techniques. This procedure has been applied in 5 cases of
      complicated parenchymal air leaks. Complete or substantial partial control was
      achieved in all cases. There were no complications.

PMID- 8267435
TI  - Effects of graded reductions in internal mammary artery bypass flow on left
      ventricular function.
AB  - This study investigated the controversial relationship between reduction in
      internal mammary artery (IMA) graft blood flow and left ventricular function in a
      canine model. Ten dogs underwent IMA grafting to the left anterior descending
      coronary artery. The left anterior descending coronary artery proximal to the IMA
      graft was intermittently occluded while IMA flow was mechanically controlled for
      5-minute periods to produce four IMA flow groups representing 100%, 75%, 50%, and
      25% of unoccluded IMA graft blood flow. As a control, the left ventricle was
      reperfused with native left anterior descending coronary artery flow between each
      IMA graft flow period to allow return to steady state. Sonomicrometry was used to
      obtain stroke work end-diastolic dimension relationship data for regional and
      global left ventricular function for each of the four flow groups. The global
      pressure recruitable work area relationship showed a significant rightward shift
      at 25% of unoccluded IMA flow, whereas the regional pressure recruitable work
      area relationship shifted at 50% of unoccluded IMA flow. Thus, regional
      myocardial function is more sensitive to reductions in IMA blood flow than is
      global left ventricular performance, and there is a significant IMA flow reserve
      for global left ventricular function.

PMID- 8267436
TI  - Acute electrical stimulation increases extramyocardial collateral blood flow
      after a cardiomyoplasty.
AB  - We hypothesized that acute electrical stimulation of a latissimus dorsi
      cardiomyoplasty would augment the collateral blood flow delivered by the skeletal
      muscle to the heart. This hypothesis was tested in an animal model (13 goats) of
      coronary artery disease. Six weeks after a cardiomyoplasty was performed,
      myocardial collateral blood flow derived from the latissimus dorsi muscle was
      measured with colored microspheres when the muscle was at rest and during
      electrical stimulation of the thoracodorsal nerve at 1.25 Hz. The area at risk
      for ischemia averaged 13.37 +/- 2.08 g (mean +/- standard error), or 18.4% of
      left ventricular mass (n = 13). At rest, significant skeletal muscle-derived
      collaterals developed in 9 animals, and formed predominantly to chronic ischemic
      myocardium (mean +/- standard error, 0.07 +/- 0.02 mL.g-1 x min-1; n = 9), rather
      than infarct (0.03 +/- 0.02 mL.g-1 x min-1; n = 5), or normal myocardium (0.0005
      +/- 0.0001 mL.g-1 x min-1; n = 9). Stimulation increased skeletal muscle-derived
      collateral blood flow to chronic ischemic areas to 0.38 +/- 0.09 mL.g-1 x min-1
      (n = 9) (p < 0.05). During stimulation, the collateral flow was greater in the
      epicardium (0.46 +/- 0.11 mL.g-1 x min-1) than in endocardium (0.14 +/- 0.09 mL.g
      1.min-1) (p < 0.05). This study demonstrates that electrical stimulation of a
      latissimus dorsi cardiomyoplasty increases extramyocardial collateral blood flow
      to chronic ischemic myocardium.

PMID- 8267437
TI  - Changes in ventricular geometry early after Fontan operation.
AB  - Acute removal of a ventricular volume overload, in the face of relatively
      unchanging ventricular mass, results in geometric alterations that can impair
      diastolic ventricular performance after Fontan operation. We investigated whether
      geometric alterations were (1) more severe after Fontan operation than after hemi
      Fontan operation, (2) more severe in infants than in children, and (3) more
      severe in the morphologic right ventricle than in the morphologic left ventricle.
      We studied 22 patients, 11 with hypoplastic left heart syndrome and 11 with a
      functionally single morphologic left ventricle. After Fontan operation, right
      ventricular end-diastolic volume declined by 52% from 36.6 +/- 12.2 to 17.5 +/-
      9.3 mL. Right ventricular wall thickness increased from 6.8 +/- 1.3 to 7.5 +/-
      1.8 mm. Left ventricular end-diastolic volume diminished by 40% from 57.6 +/-
      23.3 to 34.8 +/- 17.6 mL. Left ventricular wall thickness increased from 7.0 +/-
      2.1 to 8.7 +/- 1.9 mm. The alterations in right ventricular geometry are more
      marked early after Fontan operation than early after the hemi-Fontan procedure.
      Geometric alterations in the left ventricle appear to be more severe in infants
      than in children. Finally, alterations in the morphologic right ventricle appear
      to be of similar magnitude to those in the morphologic left ventricle.

PMID- 8267438
TI  - Effect of altering pump flow rate on cerebral blood flow and metabolism in
      infants and children.
AB  - The effects of reduced pump flow rate (PFR) on cerebral blood flow, cerebral
      oxygen consumption (CMRO2), oxygen extraction, cerebral vascular resistance, and
      total body vascular resistance were examined in 27 pediatric patients during
      hypothermic cardiopulmonary bypass (hCPB). During steady state hCPB the
      extracorporeal flows were randomly adjusted to a conventional PFR and a reduced
      PFR for each patient. The reduced pump flow rates were dictated by surgical
      needs. Cerebral blood flow measured using Xenon 133 clearance, and CMRO2 and
      oxygen extraction were calculated. Our results demonstrated that cerebral blood
      flow and CMRO2 are unchanged if pump flow rates are reduced by 35% to 45% of
      conventional PFRs at moderate and deep hypothermic temperatures. Reductions in
      PFR of 45%-70% from conventional PFRs affect the brain differently during either
      moderate or deep hCPB. At moderate hCPB (26 degrees to 29 degrees C), reductions
      in PFRs of 45% to 70% resulted in a significant decrease in cerebral blood flow
      and CMRO2, whereas oxygen extraction increased in a compensatory manner. During
      deep hCPB (18 degrees to 22 degrees C), PFR reductions of 45% to 70% of
      conventional PFR significantly reduced cerebral blood flow and CMRO2 but did not
      increase oxygen extraction, suggesting that at deep hypothermic temperatures,
      cerebral blood flow and CMRO2 exceed cerebral metabolic needs. Cerebral vascular
      resistance increased significantly with decreasing temperature but was not
      affected by pump flow reductions. We have derived indices for minimal acceptable
      low-flow cardiopulmonary bypass based on the known effects of temperature on
      cerebral metabolism and have speculated on its utility based on our limited data
      and a literature review.

PMID- 8267439
TI  - Improved distal circulatory support for repair of descending thoracic aortic
      aneurysms.
AB  - Bleeding is a well-known problem when cardiopulmonary bypass with full systemic
      heparinization is used for distal support during aortic cross-clamping. The
      recent advent of heparin-coated cardiopulmonary bypass equipment prompted our
      review of 91 consecutive patients who underwent repair of descending thoracic and
      thoracoabdominal aortic aneurysms. Two different surgical techniques were used:
      42 of 91 patients had simple aortic cross-clamping and rapid reanastomosis,
      whereas 49 of 91 had distal support using all heparin-coated perfusion equipment
      with low systemic heparinization (100 IU/kg body weight; activated coagulation
      time > 180 seconds). Baseline parameters, location (thoracoabdominal: 28/91;
      31%), and type of aneurysm (ruptured: 14/91; 15%) were similar in both groups.
      Cross-clamp time was 37 +/- 22 minutes for support versus 29 +/- 13 minutes for
      simple clamping (p < 0.05). There were fewer revisions due to bleeding for
      support (1/49 patients; 2%) versus simple (4/42; 10%; p < 0.05) and fewer
      patients with impaired renal function requiring temporary hemofiltration for
      support (4/49 patients; 8%) versus simple (6/42; 14%). Hospital mortality was
      lower for support (5/49; 10%) versus simple (8/42; 19%). Transfusion requirements
      during operation were 3,732 +/- 3,458 mL for simple versus 3,392 +/- 2,058 mL for
      support (not significant). Chest tube drainage totaled 982 +/- 1,102 mL for
      simple versus 720 +/- 618 mL for support (not significant). The total volume
      requirements were 8,156 +/- 4,753 mL for simple versus 7,495 +/- 3,342 mL for
      support (not significant) during operation and 4,416 +/- 2,422 mL for simple
      versus 3,380 +/- 1,432 mL for support (p < 0.025) during the 24 hours after
      operation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267440
TI  - Heart and lung grafts harvested en bloc: operative technique, utilization, and
      results.
AB  - Combined heart and lung transplantation has been shown to provide successful
      therapy for patients with end-stage heart and lung disease. The improved success
      of lung transplantation has resulted in increasing number of potential recipients
      and longer waiting times. Maximal utilization of all three thoracic organs is no
      longer a casual goal but of utmost necessity. We devised a new technique that
      improves operative visualization, decreases dissection time, and ensures
      excellent preservation of all three thoracic organs. Bench dissection after
      extraction of this heart-lung block allows the thoracic and cardiac surgeons to
      agree on precise dissection of the left atrium and adequate pulmonary venous and
      atrial cuff. This technique has been used in 48 of our last 50 harvests with
      excellent results. Utilization of heart and lungs has been 93% and 74%,
      respectively.

PMID- 8267441
TI  - Resection of an intracardiac metastasis from malignant teratoma of the testis.
AB  - Nonseminomatous germ cell testicular neoplasm is a disease cured primarily by
      platinum-based combination chemotherapy. Operation is reserved for those patients
      who continue to harbor residual masses after chemotherapy. Locoregional lymph
      nodes and lungs are common sites for residual deposits. Intracardiac metastases
      are very rare. We report a case of successful resection of bilateral lung and
      single intracardiac secondary deposits from a malignant teratoma, treated by
      orchidectomy 6 years previously.

PMID- 8267442
TI  - Primary leiomyosarcoma of the thoracic aorta presenting as a contained rupture.
AB  - Primary neoplasms of the aorta are rare and usually present with signs and
      symptoms due to intraluminal obstruction. A case of a 48-year-old man who
      presented with a contained rupture of the thoracic aorta secondary to a
      leiomyosarcoma is reported.

PMID- 8267443
TI  - Thoracoscopic resection of pericardium for symptomatic congenital pericardial
      defect.
AB  - Congenital defects of the pericardium are rare. Surgical treatment is recommended
      to relieve symptoms and to prevent cardiac herniation and strangulation. The case
      of a symptomatic pericardial defect due to a dynamic obstruction of the coronary
      arteries is described. The diagnosis was suggested by plain chest film,
      echocardiography, and cardiac catheterization. Confirmation and successful
      surgical management were accomplished by video-assisted thoracoscopic
      pericardiectomy.

PMID- 8267444
TI  - Complications of retained epicardial pacing wires: an unusual bronchial foreign
      body.
AB  - The use of temporary epicardial pacing wires after open cardiac operations has
      been associated with a low morbidity. Complications can be divided into those
      encountered during placement, removal, or retention of these wires. We describe
      herein an unusual complication of a retained temporary epicardial pacing wire
      presenting as a posterior mediastinal mass and as a bronchial foreign body.

PMID- 8267445
TI  - Right ventricle-to-aorta conduit in pulmonary atresia with intact ventricular
      septum and coronary sinusoids.
AB  - A 20-month-old girl with pulmonary atresia, intact ventricular septum, and
      ventriculocoronary connections underwent successful interposition of a right
      ventricle-to-aorta conduit and Fontan operation. The patient initially had a
      modified Blalock-Taussig shunt at birth and subsequently a bidirectional Glenn
      shunt at 8 months of age. After Fontan and right ventricle-to-aorta conduit
      placement, the suprasystemic right ventricular pressure dropped to systemic
      levels without causing myocardial injury. Additionally, the right ventricular
      cavity enlarged. We believe that the use of a right ventricle-to-aorta conduit
      should provide a valuable alternative and improve the outlook of certain patients
      with pulmonary atresia, intact ventricular septum, and ventriculocoronary
      connections.

PMID- 8267446
TI  - Use of retrograde cold crystalloid cardioplegia in a patient with unexpected cold
      agglutination.
AB  - Undetected cold agglutinins were encountered in a patient undergoing coronary
      artery bypass grafting using antegrade cold blood cardioplegia. Macroemboli were
      infused into the coronary arterial tree. These were flushed out by the use of
      retrograde cold crystalloid cardioplegia. Activated cold agglutinins may be
      hazardous in cold blood cardioplegia.

PMID- 8267447
TI  - Anomalous pulmonary venous drainage of the right lung.
AB  - An unusual case of anomalous drainage of the right lung is described. The right
      superior pulmonary vein drained into the superior vena cava, and the middle and
      lower pulmonary veins drained into the inferior vena cava. Repair was achieved by
      creating a pericardial baffle that drained the inferior vein and the orifice of
      the superior vena cava through a surgically created atrial septal defect. The
      superior vena cava was transected and the distal portion anastomosed to the right
      atrial appendage.

PMID- 8267448
TI  - Mixed type of total anomalous pulmonary venous connection with hemi-pulmonary
      vein atresia.
AB  - This reports a successfully corrected case of an 8-day-old baby who had a rare
      mixed type of total anomalous pulmonary venous connection in which the left
      pulmonary vein connected to the portal vein and the right one was atretic as
      demonstrated by pulmonary artery wedge angiography. The left common pulmonary
      vein and right pulmonary veins were anastomosed to the left atrium, separately.
      The patient tolerated the operation and has been well. Early total repair after
      accurate diagnosis was successful for this rare combination of anomalous
      pulmonary venous connection.

PMID- 8267449
TI  - Aortobronchial fistula after unilateral lung transplantation.
AB  - An aortobronchial fistula resulting in massive hemoptysis developed in a 48-year
      old man 13 months after unilateral lung transplantation. His posttransplantation
      recovery was complicated by bronchial dehiscence requiring revision and
      subsequent stricture formation treated by granulation tissue excision, placement
      of endobronchial stents, dilation, and laser photoablation. Early and aggressive
      treatment using these modalities is necessary in the successful management of
      airway complications after pulmonary transplantation.

PMID- 8267450
TI  - Carcinoid crisis after biopsy of a bronchial carcinoid.
AB  - Pulmonary carcinoids are rarely associated with carcinoid syndromes and even less
      commonly with carcinoid crisis. Somatostatin analogues can control carcinoid
      syndrome or crisis with tumors of gastrointestinal origin. We report the
      successful use of a somatostatin analogue in preventing carcinoid crisis at the
      time of resection of an "active" bronchial carcinoid tumor.

PMID- 8267451
TI  - Congenital absence of the pericardium: displacement of the heart associated with
      tricuspid insufficiency.
AB  - This report describes a patient with congenital absence of the left pericardium
      with displacement of the heart into the left pleural space and associated
      tricuspid insufficiency. Excision of the ruptured chordae, plication of the flail
      anterior leaflet, and tricuspid annuloplasty rendered a competent tricuspid
      valve.

PMID- 8267452
TI  - Successful orthotopic transplantation of a fresh tricuspid valve homograft in a
      human.
AB  - We report a successful transplantation of a human tricuspid valve in a human. We
      used a fresh tricuspid homograft with its chordae tendineae and papillary
      muscles, harvested 5 days earlier under sterile conditions from a multiorgan
      donor a few minutes after cardiectomy (the heart was not suitable for cardiac
      transplantation) and immediately stored at 4 degrees C. We elected to implant the
      homograft in a young heroin addict. Our experience demonstrates that the
      implantation of an atrioventricular homograft in the orthotopic position is
      technically feasible and can achieve good results, at least in the short term.

PMID- 8267453
TI  - Donor lung procurement: assessment and operative technique.
AB  - Given the relative scarcity of suitable donors and the widespread application of
      cardiac and pulmonary transplantation, it is imperative that a heart and two
      lungs be extracted from each donor. From increasing clinical experience and
      laboratory investigation in lung preservation, more flexible criteria for the
      assessment of potential lung donors are emerging. In this communication, we
      present our current criteria of donor lung suitability, and a simple and reliable
      technique of combined cardiopulmonary extraction that has provided suitable heart
      and lung grafts with excellent preservation, used in our last 150 donor organ
      procurements.

PMID- 8267454
TI  - Outflow reconstruction of tetralogy of Fallot using a Gore-Tex valve.
AB  - The right ventricular outflow tract was reconstructed in patients with tetralogy
      of Fallot using a wide transannular patch bearing a large unicuspid or bicuspid
      valve. The shape of the valve was designed to limit the degree of pulmonary
      regurgitation. The characteristics of the valve and the water-repellent nature of
      the polytetrafluoroethylene sheet make calcification and pseudointimal formation
      less common than with traditional bioprosthetic valves.

PMID- 8267455
TI  - Thoracoscopic clipping of patent ductus arteriosus in premature infants.
AB  - Patent ductus arteriosus is a frequent indication for surgical intervention in
      preterm infants. Commonly this operation is performed through a dorsolateral
      thoracotomy. In an animal trial (piglets smaller than 1,400 g) instruments and
      technique for thoracoscopic clipping of patent ductus arteriosus were developed.
      Since January 1993, 3 premature infants have been treated with this new minimally
      invasive procedure. The instruments and the surgical technique are demonstrated.

PMID- 8267456
TI  - Internal mammary artery for arterial pressure monitoring after pediatric cardiac
      operations.
AB  - Establishing and maintaining arterial access in pediatric cardiac operations is a
      frequent and sometimes frustrating problem. We have modified a procedure commonly
      used in our research laboratory for arterial pressure monitoring and applied it
      successfully to the pediatric cardiac surgical patient. The internal mammary
      artery can provide reliable arterial access in the postoperative period.

PMID- 8267457
TI  - The first transplantation of the lung in a human revisited.
AB  - The first homotransplantation of the lung in a human was performed in early 1963,
      thirty years ago. It is the purpose of this review to evaluate the significance
      of this event and to determine its effects on the further development of lung
      transplantation.

PMID- 8267458
TI  - Surgical management of aortic valve injury after nonpenetrating trauma.
AB  - A case report and a literature review of the patients who underwent surgical
      repair of an aortic valve injury secondary to nonpenetrating trauma are
      presented. Thirty-seven patients (32 male and 5 female patients) with a median
      age of 43 years sustained either blunt chest trauma (34 patients) or muscular
      strain (3 patients) as a cause of injury. Primary repair was undertaken on 4
      patients before 1964 (when the first aortic valve replacement was performed for
      this condition) and on 6 other patients after 1964. In the former group, 2
      patients died because of heart failure and 1 subsequently required a prosthesis.
      The last patient had an excellent result at 17 years. In the latter group, 1
      patient with a complex lesion had persistent moderate aortic regurgitation. The 5
      remaining patients had a simple lesion to the valve and showed excellent results
      on follow-up evaluation (ranging from 6 months to 6 years). Aortic valve
      replacement successfully corrected the valvular dysfunction in 26 patients.
      Except for 1 case of hemolytic anemia, specific complications of prosthesis were
      not encountered, but median follow-up of this review was only 9 months. A
      modulated approach to this condition is proposed where primary repair is selected
      for cases with a simple tear or avulsion of one cusp. Intraoperative control of
      the repair by transesophageal echocardiography increases the safety of this
      approach. Valve replacement is indicated for more complex lesions or for
      ineffective primary repair as assessed by intraoperative
      echocardiography.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267459
TI  - 1986: Early dilation in the treatment of esophageal disruption. Updated in 1993.

PMID- 8267460
TI  - Practice guidelines in cardiothoracic surgery. Council of the Society of Thoracic
      Surgeons.

PMID- 8267461
TI  - Retrograde low-dilution continuous normothermic blood cardioplegia.

PMID- 8267462
TI  - Early use of internal thoracic artery.

PMID- 8267463
TI  - Heart surgery in underdeveloped countries: success in Panama and Romania.

PMID- 8267464
TI  - Surgical difficulty in localized supravalvar aortic stenosis.

PMID- 8267465
TI  - Cardiac operation in patients after completed stroke.

PMID- 8267466
TI  - Coronary sinus cannulation: a technique to overcome an obstructing thebesian
      valve.

PMID- 8267467
TI  - Erosion of epicardium by intrapericardially placed ICD patch.

PMID- 8267468
TI  - Anesthesia, the brain, and cardiopulmonary bypass.
AB  - The etiology and incidence of neurologic injury occurring after cardiac
      operations employing cardiopulmonary bypass is reviewed. Results of studies
      demonstrating the role of microemboli generated by pump oxygenators, and evidence
      for the efficacy of arterial line filtration to decrease delivery of emboli into
      the cerebral circulation and to decrease postoperative neuropsychological
      dysfunction, are similarly reviewed. The impact of different strategies for
      management of pH during moderate hypothermic cardiopulmonary bypass on cerebral
      blood flow and coupling of cerebral flow and metabolism, as well as their impact
      on the incidence of postoperative cognitive dysfunction, are also discussed,
      along with the results of studies examining the efficacy of various agents
      including thiopental, nimodipine, and nafamostat to decrease cognitive
      dysfunction subsequent to bypass.

PMID- 8267469
TI  - Effect of deep hypothermia and circulatory arrest on cerebral blood flow and
      metabolism.
AB  - The primary goal of monitoring cerebral blood flow and metabolism is to improve
      our understanding of the association with cardiopulmonary bypass and deep
      hypothermic circulatory arrest so that effective brain protection strategies can
      be developed and employed. A review of our cerebral blood flow/cardiopulmonary
      bypass database, presently totaling 275 neonates and infants, for the purposes of
      this publication, reveals certain trends and some conclusions that can be drawn.
      Deep hypothermic circulatory arrest continues to be a factor in the delayed
      recovery of cerebral blood flow and metabolism in these patients. Examining flow
      and metabolism serially in the postoperative period shows that in the majority of
      patients, flow, metabolism and autoregulation return to normal within 24 hours
      after operation. Some patients' cerebral oxygen metabolism is unable to exert a
      protective response of increasing extraction in the setting of low cerebral blood
      flow. We have also observed that in the setting of low cardiac output after
      cardiac repair, cerebral blood flow is low. It is therefore likely that low
      cardiac output and pressure-passive cerebral blood flow potentiate brain ischemia
      after cardiopulmonary bypass and operation in some patients. We have also
      examined in our series of 275 patients selective neuroprotection strategies for
      their potential for improving recovery of cerebral blood flow and cerebral
      metabolism. Duration of cooling on cardiopulmonary bypass correlates directly
      with suppression of metabolism due to hypothermia. Low-flow cardiopulmonary
      bypass instead of deep hypothermic circulatory arrest, and topical brain cooling
      with ice during deep hypothermic circulatory arrest, improve cerebral blood flow
      and cerebral metabolic recovery.

PMID- 8267470
TI  - Review of current research at Boston Children's Hospital.
AB  - Both clinical and laboratory studies are being undertaken to investigate the
      deleterious neurologic and developmental effects associated with cardiopulmonary
      bypass, hypothermia, and circulatory arrest in the neonate and infant. A
      prospective, randomized clinical study of 171 neonates and young infants compared
      circulatory arrest with low-flow bypass (50 mL.kg-1.min-1). Circulatory arrest
      was associated with a higher incidence of early postoperative seizures as well as
      greater release of creatine kinase-BB. There was a strong correlation between
      duration of circulatory arrest and seizures (p = 0.004). The late consequences of
      these findings will be known at the completion of developmental assessment of all
      patients at 1 and 4 years of age. Laboratory studies have used a miniature piglet
      model that closely replicates clinical circulatory arrest. High-energy phosphate
      stores determined by magnetic resonance spectroscopy were maintained in animals
      undergoing 1 hour of low-flow bypass but became undetectable after 32 minutes of
      a 1-hour period of circulatory arrest. However, they returned to baseline within
      3 hours of reperfusion as did cerebral blood flow and metabolism determined by
      microsphere studies. Piglets undergoing 1 hour of circulatory arrest showed more
      rapid recovery of cerebral adenosine triphosphate content and intracellular pH
      when managed with the pH-stat strategy during hypothermic bypass than with the
      more alkaline alpha-stat strategy. Other laboratory studies have examined
      pharmacologic methods of reducing cerebral injury associated with circulatory
      arrest including aprotinin, anti-CD18, neuronal receptor antagonists (MK801,
      NBQX), and blockade of glutamate release with adenosine in a cerebroplegia
      solution. These studies have suggested a number of promising approaches to
      improving the technique of circulatory arrest.

PMID- 8267472
TI  - Pulsatile low-flow perfusion for enhanced cerebral protection.
AB  - We examined the oxygen tension, carbon dioxide tension, and pH in canine brains
      under profound hypothermia to evaluate the effects of perfusion (circulatory
      arrest for 1 hour; 25 and 50 mL.kg-1 x min-1 for 2 hours) with and without
      pulsatile assistance. The effects of pulsatile flow on cerebral blood flow and
      metabolism were also evaluated in dogs supported by low-flow perfusion (25 mL.kg
      1 x min-1) for 2 hours. Profound hypoxia occurred in the brain after 20 to 60
      minutes of circulatory arrest. Brain tissue acidosis with hypercapnia was
      moderated by perfusion at a rate of flow of 50 mL.kg-1 x min-1. Pulsatile low
      flow perfusion (25 mL.kg-1 x min-1) moderated cerebral hypercapnia and made the
      cerebral metabolism aerobic without affecting the total cerebral blood flow and
      consumption of oxygen.

PMID- 8267471
TI  - Cerebral hemodynamics during cardiopulmonary bypass in children using near
      infrared spectroscopy.
AB  - We describe a new noninvasive method using near-infrared spectroscopy for
      monitoring cerebral hemodynamics during cardiopulmonary bypass in children. All
      patients were undergoing open heart operations for repair of congenital heart
      defects. Standardized anesthesia, an alpha-stat method of blood gas management,
      and nonpulsatile flow were used in all cases. All measurements during bypass were
      made after steady-state conditions had been reached. Cerebral blood flow was
      measured on 13 occasions in 4 children, aged between 4 and 10 months (median, 5
      months). Values of 15.9 to 53.5 mL x 100 g-1 x min-1 were obtained. Cerebral
      blood volume was measured in 1 patient, aged 4 months. Volumes of 4.3 to 8.0 mL x
      100 g-1 were obtained on bypass at full pump flow (2.4 L.min-1 x m-2). On bypass
      at half flow, the volume increased to 14.7 mL x 100 g-1. Change in cerebral blood
      volume with changing carbon dioxide tension (CBVR) was measured in 13 patients
      aged from 1 to 90 months (median, 13.5 months). Preoperatively, CBVR was 0.12 +/-
      0.07 mL x 100 g-1 x kPa-1 and was independent of mean arterial pressure, which
      remained between 40 and 80 mm Hg in all cases. During hypothermic bypass (25
      degrees C), CBVR was significantly reduced to 0.05 +/- 0.02 mL x 100 g-1 x kPa-1.
      In addition, there were three values at mean arterial pressure of lower than 40
      mm Hg in which CBVR was negative (-0.04 +/- 0.01 mL x 100 g-1 x kPa-1). We
      conclude that near-infrared spectroscopy is useful for the noninvasive
      investigation of cerebral hemodynamics during cardiopulmonary bypass.

PMID- 8267473
TI  - Transcranial Doppler monitoring of cerebral perfusion during cardiopulmonary
      bypass.
AB  - Profound hypothermic circulatory arrest and profound hypothermia with continuous
      low-flow cardiopulmonary bypass are used to facilitate repair of complex
      congenital heart lesions. Extended periods of profound hypothermic arrest may
      impair cerebral function and metabolism and produce ischemic brain injury. Low
      flow bypass has been advocated as preferable to profound hypothermic arrest with
      respect to neurologic outcome as it maintains continuous cerebral circulation
      during repair of heart defects. Several studies have suggested that low-flow
      bypass produces equal degrees of cerebral injury as corresponding periods of
      circulatory arrest. Transcranial Doppler sonography has enabled the noninvasive
      study of cerebral perfusion during operations using either circulatory arrest or
      low-flow bypass. Although these studies have demonstrated the presence of
      cerebral perfusion at low perfusion pressures, evidence exists to suggest that
      cerebral perfusion abruptly ceases at cerebral perfusion pressures of 7 to 9 mm
      Hg and is unrelated to pump flow rate. Transcranial Doppler sonography is a
      useful tool for monitoring cerebral perfusion during low-flow bypass, and future
      studies with this modality may help to develop improved modes of cerebral
      protection during repair of complex congenital heart lesions.

PMID- 8267474
TI  - Cerebral lactate release after circulatory arrest but not after low flow in
      pediatric heart operations.
AB  - Arteriovenous (jugular bulb) differences in blood lactate were followed
      throughout the procedure and until 18 hours postoperatively in 17 children
      undergoing congenital heart operations during profound hypothermia. Transcranial
      Doppler sonography was used to monitor changes in blood flow velocity in the
      middle cerebral artery. Ten children had a period of total circulatory arrest (39
      +/- 6 minutes) during profound hypothermia (arrest group). Another 7 children had
      continuous but reduced pump flow (0.6 to 1.2 L/m2) throughout hypothermic
      cardiopulmonary bypass (low-flow group). The mean age was 7.3 +/- 1.3 months in
      the arrest group and 7.9 +/- 2.2 months in the low-flow group. The mean time on
      bypass was 90 +/- 10 minutes in the arrest group and 75 +/- 9 minutes in the low
      flow group. The velocity of blood flow in the middle cerebral artery decreased
      significantly (p < 0.05) in both groups to less than 50% of the preoperative
      level during hypothermia and increased during and after rewarming. Differences in
      blood lactate level were significantly less than zero (p < 0.05) from the start
      of rewarming until 3 hours after the end of cardiopulmonary bypass in the arrest
      group, whereas differences in blood lactate level remained close to zero in the
      low-flow group. We conclude that circulatory arrest during profound hypothermia
      is followed by a period with release of lactate from the brain, indicating
      anaerobic cerebral metabolism and possibly disturbed cerebral aerobic metabolism.
      This study argues for the avoidance of circulatory arrest whenever possible.

PMID- 8267475
TI  - Low-flow cardiopulmonary bypass and cerebral protection: a summary of
      investigations.
AB  - A research program in cerebral ischemia was initiated by our laboratory to
      determine optimal strategies for cerebroprotection. Four studies relating to
      cerebroprotection using nuclear magnetic resonance spectroscopy in a sheep model
      of hypothermic cardiopulmonary bypass are summarized. These showed, first, that
      low-flow bypass, with a flow as low as 10 mL.kg-1 x min-1, maintained normal
      cerebral metabolism; second, that hypothermia increases the high-energy phosphate
      content and the intracellular pH of the brain; third, that hyperglycemia causes a
      profound intracellular acidosis; and, finally, that barbiturates prevent the
      normal increase in high-energy phosphates associated with hypothermia.

PMID- 8267476
TI  - Protection of the brain during hypothermic perfusion.
AB  - The adequacy of the circuits for brain perfusion has been explored by hemodynamic
      assessment using the ability of the brain to autoregulate blood flow as an
      indicator, and by morphologic observation using carbon black or Evans blue
      infusion into the brain perfused antegradely or retrogradely. It is concluded
      that the safe pressure of cerebral perfusion needed to maintain cerebral
      integrity is between 40 and 50 mm Hg in both normothermic and hypothermic
      perfusions, a pressure that can be generated by nonpulsatile pump flows through
      the pump greater than 40 mL.kg-1 x min-1. Morphologic studies revealed
      development of focal infarctions in the brain and destruction of the blood-brain
      barrier by retrograde cerebral perfusion. The retrograde approach, therefore, is
      definitely inferior to the antegrade method. Antegrade perfusion for 90 minutes,
      however, produced minimal cerebral edema, suggesting the need for further
      improvement even in techniques of antegrade perfusion.

PMID- 8267477
TI  - Retrograde cerebral perfusion using pulsatile flow under conditions of profound
      hypothermia.
AB  - We investigated the effects of pulsatile flow for retrograde cerebral perfusion
      under profound hypothermia. Total cardiopulmonary bypass was carried out in adult
      mongrel dogs to induce hypothermia. One hour of total circulatory arrest was then
      performed at 20 degrees C in the control group of 6 dogs. In another group of 6
      dogs, after cardiac arrest was obtained at 20 degrees C, retrograde cerebral
      perfusion with nonpulsatile flow was performed through both sides of the internal
      maxillary vein for 60 minutes; in a third group of 6 dogs, retrograde pulsatile
      perfusion was continued for 60 minutes. At the end of either retrograde perfusion
      or total circulatory arrest for 60 minutes, cerebrospinal fluid pressure and
      blood flow in the cerebral tissues were measured, and cerebral tissues were
      collected to measure water and adenosine triphosphate content. A significant
      difference was found for water content between the group undergoing retrograde
      perfusion with pulsatile flow as opposed to nonpulsatile flow. Cerebral tissues
      in the group perfused retrogradely with nonpulsatile flow contained more water
      than in the group perfused with pulsatile flow. Cerebrospinal fluid pressure was
      lower in the group perfused retrogradely with pulsatile flow when compared with
      nonpulsatile flow, but no significant difference could be found. As for cerebral
      flow and adenosine triphosphate content, no significant differences could be
      found between the groups perfused retrogradely with pulsatile or with non
      pulsatile flow. Values were always higher, nonetheless, in the groups perfused
      with pulsatile flow. We conclude that retrograde cerebral perfusion with
      pulsatile flow, when used under conditions of profound hypothermia, possesses
      more cerebroprotective effects than does non-pulsatile perfusion or circulatory
      arrest.

PMID- 8267478
TI  - Cytokine production and hemofiltration in children undergoing cardiopulmonary
      bypass.
AB  - Multiorgan dysfunction still occurs after cardiopulmonary bypass and remains a
      major cause of morbidity and mortality, especially in the pediatric age group.
      This is consequent upon the so-called systemic inflammatory response to bypass
      with an increase in inflammatory mediators. Hemofiltration may be able to
      attenuate the effects of this response by elimination of some or all of these
      mediators. We undertook a prospective, randomized study to investigate the effect
      of hemofiltration on plasma levels of the cytokines tumor necrosis factor alpha,
      interleukin-8, and interleukin 6 in 18 infants and children undergoing deep
      hypothermic bypass. Serial plasma samples were taken before, during, and after
      bypass. Assay of the plasma samples revealed presence of the cytokines in a
      number of subjects in both groups, in some cases before operation. There were
      significant reductions in levels of tumor necrosis factor after hemofiltration,
      with no reduction noted in the group not undergoing hemofiltration. A similar
      difference (p < 0.05) was detected in the levels of interleukin-6 between the two
      groups after bypass, although this was largely due to changes in 2 subjects.
      Interleukin-8 was detected in a small number of subjects insufficient for
      statistical analysis, but with higher values in the group undergoing
      hemofiltration. We conclude that hemofiltration has the potential to remove
      cytokines from the circulation, with consequent beneficial effects.

PMID- 8267479
TI  - Hemofiltration modifies complement activation after extracorporeal circulation in
      infants.
AB  - Complement and fibrinolytic factors were measured in 9 infants undergoing
      hemofiltration immediately after cardiopulmonary bypass in an attempt to reduce
      activation of these systems. Plasma levels of C3a, C5a, and terminal complement
      complexes increased during bypass by 460%, 85%, and 745%. Plasma levels were
      reduced after hemofiltration in 8 of the 9 infants, and C3a and C5a fractions
      were recovered in the ultrafiltrate. The observed activation of the fibrinolytic
      system seemed to be unaltered by hemofiltration. Fibrinolytic factors were not
      filtered. Our study shows that increased concentrations of complement factors in
      the plasma after bypass in infants may be reduced by hemofiltration.

PMID- 8267480
TI  - Ultrafiltration and modified ultrafiltration in pediatric open heart operations.
AB  - The capillary leak associated with cardiopulmonary bypass results in an increase
      in content of water in the tissues measurable by an increase in total body water
      after cardiac operation. Following work by Magilligan in the 1970s,
      ultrafiltration was introduced during bypass as a means of hemoconcentrating
      patients and potentially removing water from the tissues. Conventional methods
      proved inconsistent; thus, we modified the technique to ultrafilter the patients
      immediately after cessation of bypass. Modified ultrafiltration takes 10 minutes
      and results in an elevation of the on-bypass hematocrit to about 35% or 40%. In
      pilot studies comparing bypass in absence of ultrafiltration with conventional
      ultrafiltration and modified ultrafiltration, only the modified technique was
      seen reliably to reduce the elevation in total body water to only 4%, within a
      narrow range. Subsequent prospective studies confirmed the reduction in
      accumulation of total body water and also demonstrated a reduction in blood loss
      and in requirements for blood transfusion. Systolic blood pressure was observed
      to increase uniformly in all patients undergoing modified ultrafiltration. This
      effect was investigated and found to be associated with a marked increase in
      cardiac index, no change in systemic vascular resistance, a decrease in heart
      rate, and a marked decrease in pulmonary vascular resistance. Recently, we have
      demonstrated an increase in contractility and a decrease in myocardial wall
      volume. The modified technique of ultrafiltration has been employed successfully
      in more than 400 patients in our institution, and represents an excellent option
      for perioperative management of both accumulation of fluid in the tissues and
      hemodynamics after hypothermic bypass.

PMID- 8267481
TI  - Evaluation of hepatic injury arising during fluconazole therapy.
AB  - Previous reports have described hepatotoxicity associated with ketoconazole
      therapy. There is also concern that therapy with fluconazole might cause the same
      side effect as ketoconazole. We describe two patients who developed unexplained
      liver test abnormalities after beginning fluconazole therapy. To determine
      whether fluconazole might have been responsible, liver biopsies were performed.
      Specimens from both patients demonstrated an absence of hepatocyte necrosis,
      which, if present, would have necessitated discontinuation of fluconazole
      therapy. A critical review of other case reports of fluconazole-associated
      hepatitis also failed to produce a consistent picture. Our experience indicates
      that a liver biopsy may be useful in selected patients to exclude clinically
      relevant hepatotoxicity due to fluconazole therapy and to allow its continued
      use.

PMID- 8267482
TI  - The empathic physician.

PMID- 8267483
TI  - Changes in undergraduate medical education.

PMID- 8267484
TI  - Sex, AIDS, and the elderly.

PMID- 8267485
TI  - Clinical skills in the 21st century.

PMID- 8267486
TI  - Gram-positive organisms and sepsis.
AB  - In recent years, the importance of gram-negative organisms in the genesis of
      sepsis has been emphasized. However, this emphasis may no longer be correct;
      recent studies show an increasing incidence of gram-positive sources of sepsis,
      and its is possible that these cases may predominate in the coming years. This
      increase results from more than just a greater prevalence of infection--it
      appears that gram-positive organisms may also be more virulent in fomenting the
      disease, as can be evidenced by the emergence of streptococcal toxic shock
      syndrome and the resurgence of acute rheumatic fever. This may result from the
      ability of gram-positive organisms to produce more inflammation-causing cell wall
      constituents, as well as unbound exotoxins. Despite the recent emphasis on gram
      negative causes, sepsis resulting from gram-positive sources is increasingly
      common. Research on these causes of sepsis should be encouraged.

PMID- 8267487
TI  - The benefits of aspirin in acute myocardial infarction. Still a well-kept secret
      in the United States.
AB  - Acute myocardial infarction (MI) remains far and away the leading cause of death
      in the United States, and is responsible for approximately 500,000 annual
      fatalities. However, mortality due to MI has declined substantially in recent
      decades, owing to advances in treatment as well as prevention. Low-dose aspirin
      as well as thrombolytic therapy given during acute evolving MI each decrease
      mortality by about one quarter. Both therapies remain underutilized in the United
      States. Aspirin can be given to virtually all patients, has a far more favorable
      safety profile than thrombolysis, and confers a comparable benefit at a small
      fraction of the cost of thrombolytic agents. The more widespread use of aspirin
      in acute MI is one of the most important and timely clinical challenges in the
      United States.

PMID- 8267488
TI  - Striking prevalence of over-the-counter nonsteroidal anti-inflammatory drug use
      in patients with upper gastrointestinal hemorrhage.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a well-established
      cause of gastrointestinal disease. There appears to be an association with peptic
      ulcer disease complications, specifically ulcer-related bleeding. Studies
      addressing this relationship have primarily evaluated prescription use of these
      agents. There has been little study of over-the-counter NSAID use in patients
      with either ulcer or nonulcer-related upper gastrointestinal hemorrhage. METHODS:
      Consecutive patients with upper gastrointestinal hemorrhage evaluated by a
      gastroenterology consultative service at a large inner-city hospital from August
      1, 1990 to July 31, 1992 were identified. The use of any prescription or over-the
      counter NSAID during the week before admission was prospectively assessed.
      Computerized pharmacy records were available for confirmation of prescription
      drug use. RESULTS: During the 2-year period of study, 421 patients were evaluated
      for upper gastrointestinal hemorrhage. The mean age of the patients was 50 years
      and the majority were male and black. The most common cause of bleeding was
      peptic ulcer disease, identified in over 50% of patients. Use of an over-the
      counter aspirin or nonaspirin NSAID was reported in 145 patients (35%) and 36
      patients (9%), respectively, during the week before admission. Prescription use
      of a nonaspirin NSAID or aspirin was reported in 56 patients (14%) and 27
      patients (6%), respectively. The overall prevalence of NSAID use during the week
      before admission was 56% (95% confidence interval, 51.2% to 60.8%). The use of
      any NSAID was significantly associated with gastric compared with duodenal ulcer
      hemorrhage, and ulcer-related bleeding compared with variceal hemorrhage.
      CONCLUSIONS: Over-the-counter NSAID use is frequent in our patient population and
      exceeds prescription use. Although ulcer-related bleeding was significantly
      associated with use of these drugs, NSAIDs were commonly used in patients with
      nonulcer-related upper gastrointestinal hemorrhage as well. Over-the-counter
      NSAID use may represent a more important cause of peptic ulcer disease and ulcer
      related hemorrhage than previously appreciated.

PMID- 8267489
TI  - A randomized trial comparing activated thromboplastin time with heparin assay in
      patients with acute venous thromboembolism requiring large daily doses of
      heparin.
AB  - BACKGROUND: The management of heparin therapy in patients who have a
      subtherapeutic activated partial thromboplastin time (APTT) despite high doses of
      heparin is problematic because the risk of heparin-associated bleeding increases
      with dose. Results of experimental studies in animals indicate that when the APTT
      response to heparin is blunted by infusion of procoagulants, dose escalation can
      be avoided without compromising efficacy, by monitoring treatment with a heparin
      assay. METHODS: A randomized, controlled trial was conducted in which patients
      with acute deep vein thrombosis, pulmonary embolism, or axillary vein thrombosis
      who required 35,000 U or more of intravenous heparin by continuous infusion
      during the previous 24 hours were allocated to have their heparin therapy
      monitored either by anti-factor Xa levels (targeted range, 0.35 to 0.67 U/mL) or
      by the APTT (targeted range, 60 to 85 seconds). Both ranges were equivalent to a
      heparin level of 0.2 to 0.4 U/mL by protamine titration. RESULTS: Three (4.6%) of
      65 patients in the anti-factor Xa group experienced recurrent venous
      thromboembolism compared with four (6.1%) of 66 patients in the APTT group
      (difference, 1.5%; confidence interval, -6.7% to 8.4%) (P = .7). There were four
      bleeding events (6.1%) in the APTT group compared with one (1.5%) in the anti
      factor Xa group (difference, 4.6%; confidence interval, -3.3% to 7.5%) (P = .4).
      During the period of heparin therapy before warfarin treatment was begun, the
      patients in the APTT group required a statistically significantly greater amount
      of heparin compared with the patients in the anti-factor Xa group. The daily mean
      APTT was subtherapeutic in patients in the anti-factor Xa group, and it was
      within the therapeutic range in the APTT group. The daily mean anti-factor Xa
      levels for both groups were within the therapeutic range. CONCLUSION: The heparin
      assay is a safe and effective method for monitoring heparin treatment in patients
      with acute venous thromboembolism whose APTT remains subtherapeutic despite large
      daily doses of heparin. In such patients, dosage escalation can be avoided if the
      heparin level is therapeutic.

PMID- 8267490
TI  - AIDS risk behaviors among late middle-aged and elderly Americans. The National
      AIDS Behavioral Surveys.
AB  - OBJECTIVES: Although 10% of all acquired immunodeficiency syndrome (AIDS) cases
      diagnosed in the United States have been among Americans aged 50 years of age or
      older, little attention has been devoted to understanding AIDS risk-taking
      behaviors among middle-aged or older Americans. This study describes the
      prevalence of AIDS risk among Americans aged 50 years of age or older. DESIGN AND
      STUDY POPULATION: We present data from the National AIDS Behavioral Surveys, two
      large cross-sectional national surveys taken in 1990-1991. MAIN OUTCOME VARIABLE:
      Prevalence of risk behaviors for human immunodeficiency virus (HIV) transmission
      and of HIV testing. RESULTS: Findings from both surveys provide replication of
      several important points. First, the prevalence of having at least one risk
      factor for HIV infection was about 10% among Americans aged 50 years or older in
      both samples. Very small proportions of Americans past the age of 50 years with a
      known behavioral risk for HIV infection used condoms during sex or had undergone
      HIV testing. At-risk Americans past the age of 50 years were one sixth as likely
      to use condoms during sex and one fifth as likely to have been tested for HIV as
      a comparison group of at-risk individuals in their 20s. CONCLUSIONS: Despite the
      fact that HIV infection is clearly present among those past the age of 50 years,
      a small proportion of individuals in this age group take behavioral risks for HIV
      infection. High-risk individuals older than 50 years are much less likely to have
      adopted AIDS prevention strategies than are younger individuals who engage in the
      same behavioral risks.

PMID- 8267491
TI  - Graduated compression stockings in the prevention of postoperative venous
      thromboembolism. A meta-analysis.
AB  - BACKGROUND: The effectiveness of graduated compression stockings in prophylaxis
      of postoperative venous thromboembolism is unclear to many physicians. Surveys
      show there is considerable variability in their use and their perceived
      effectiveness. We undertook to establish, by a systematic overview of the
      literature, the effectiveness of graduated compression stockings in the
      prophylactic setting of postoperative venous thromboembolism. METHODS: Studies
      published between 1966 and June 1992 were identified through the MEDLINE
      database, with a search in all languages, through reviews of Current Contents,
      and including references cited in identified articles. Articles were selected for
      initial analysis if they assessed the use of graduated compression stockings for
      the prophylaxis of venous thromboembolism, and if the stocking group was compared
      with an untreated or unconfounded control group. Criteria were established a
      priori, to select only studies with sound methods. On the basis of these
      criteria, 12 studies were identified for the combined analysis. Each eligible
      study was independently analyzed for the risk of development of deep venous
      thrombosis in the control and stocking groups, and this was expressed as an odds
      ratio. Odds ratios were combined across studies by means of the Mantel-Haenszel
      chi 2 procedure. The data were analyzed separately for orthopedic surgery because
      of its high risk for venous thromboembolism. RESULTS: Eleven of the 12 studies
      were in moderate-risk surgery (abdominal, gynecologic, and neurosurgery); the
      summary odds ratio was 0.28, which translates into a risk reduction of 68% (95%
      confidence interval, 53% to 73%), which is statistically significant (P < .0001).
      In the one study in orthopedic surgery that was eligible for inclusion, the odds
      ratio was 0.50 (95% confidence interval, 0.19 to 1.29; P = .17). CONCLUSIONS: The
      use of graduated compression stockings for prophylaxis of venous thromboembolism
      after moderate-risk surgery results in a significant risk reduction. It is
      unknown whether the use of graduated compression stockings in combination with
      other forms of prophylaxis results in further risk reduction. The efficacy of
      graduated compression stockings in orthopedic surgery has been assessed by only
      one study that used sound methods, hence no definitive conclusions can be made in
      these high-risk patients.

PMID- 8267492
TI  - Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic
      acid in normolipidemic patients with hypoalphalipoproteinemia.
AB  - BACKGROUND: The lipoprotein responses to conventional lipid-modifying drugs have
      not been adequately evaluated in normolipidemic patients with
      hypoalphalipoproteinemia (low levels of high-density lipoproteins). The purpose
      of this study was to compare responses to lovastatin, gemfibrozil, and nicotinic
      acid in such patients. METHODS: The first phase of the study compared lipoprotein
      responses to lovastatin and gemfibrozil in 61 middle-aged men with low levels of
      high-density lipoproteins. In the second phase, 37 patients agreed to take
      nicotinic acid; 27 patients finished this phase at a dose of 4.5 g/d. Nicotinic
      acid results were compared with those with lovastatin and gemfibrozil in the same
      patients. RESULTS: In the first phase, both drugs effectively lowered
      triglyceride levels. Gemfibrozil therapy increased high-density lipoprotein
      cholesterol levels by 10% and lovastatin by 6%, but lovastatin was much more
      effective for reducing low-density lipoprotein levels. Nicotinic acid did not
      significantly lower low-density lipoprotein levels in the second phase, but it
      raised high-density lipoprotein levels by 30%. CONCLUSIONS: Gemfibrozil therapy
      produced the least favorable response of the three drugs. Lovastatin markedly
      lowered low-density lipoprotein levels but only modestly raised levels of high
      density lipoprotein, whereas nicotinic acid had the opposite effect.
      Consequently, the latter two drugs similarly reduced low-density lipoprotein-high
      density lipoprotein ratios, although these effects were obtained in different
      ways. Between these two drugs, lovastatin therapy was more likely to reduce low
      density lipoprotein cholesterol levels to below 2.6 mmol/L (100 mg/dL), and in
      view of recent recommendations, it may be preferable to nicotinic acid for many
      normolipidemic patients with established coronary heart disease.

PMID- 8267493
TI  - Myth of substituted judgment. Surrogate decision making regarding life support is
      unreliable.
AB  - OBJECTIVE: To identify factors predicting the accuracy of surrogate decision
      making in life support decisions. DESIGN: Questionnaire. SETTING: Urban Veterans
      Affairs hospital. PATIENTS AND DESIGN: Fifty hospitalized patients and their
      chosen surrogates were given questionnaires describing life support modalities
      and four common medical scenarios in which life support would be contemplated. An
      additional 50 patients also completed the questionnaire. Patients gave their
      choices of life support in the different scenarios. Surrogates guessed the
      patients' answers (substituted judgment). Details of the patient-surrogate
      relationship were asked. Patients completed a depression inventory. MAIN RESULTS:
      Surrogates correctly guessed patients' wishes about life support overall on 59.3%
      of the questions, not better than random chance (kappa = .09). The only predictor
      of accurate surrogate decision making was specific discussion between patient and
      surrogate about life support. SECONDARY RESULTS: Patients had an overall low
      desire for life support (35%), and a majority favored euthanasia under some
      circumstances (62%). There was no relationship between depression score and
      desire for life support. CONCLUSIONS: Substituted judgment by surrogates is not
      more accurate than random chance. Discussion between patient and surrogate about
      life support correlated with more accurate substituted judgment.

PMID- 8267495
TI  - [Ventricular tachycardia].

PMID- 8267494
TI  - Glucocorticoids and the risk for initiation of hypoglycemic therapy.
AB  - PURPOSE: To quantify risk for the occurrence of hyperglycemia requiring
      initiation of hypoglycemic therapy in patients treated with oral glucocorticoids.
      PATIENTS AND METHODS: A case-control study of enrollees in the New Jersey
      Medicaid program 35 years of age or older. The 11,855 case patients had newly
      initiated treatment with a hypoglycemic agent (oral or insulin) between 1981 and
      1990. The 11,855 controls represented a random sample of other Medicaid
      enrollees. RESULTS: In patients using oral glucocorticoids, the estimated
      relative risk for development of hyperglycemia requiring treatment was 2.23 (95%
      confidence interval, 1.92 to 2.59) as compared with nonusers. Risk increased with
      increasing average daily steroid dose, in hydrocortisone-equivalent milligrams;
      the odds ratio was 1.77 for 1 to 39 mg/d, 3.02 for 40 to 79 mg/d, 5.82 for 80 to
      119 mg/d, and 10.34 for 120 mg/d or more. The estimated effects persisted after
      adjustment for a variety of potentially confounding demographic, health service
      utilization, and medication use variables. CONCLUSION: The findings of this
      population-based study quantify the risk of developing hyperglycemia requiring
      hypoglycemic therapy after oral glucocorticoid use. The magnitude of risk
      increases substantially with increasing glucocorticoid dose. These findings
      demonstrate the utility of large-scale health claims databases in defining the
      risk of important adverse drug effects.

PMID- 8267496
TI  - [Definition of ventricular tachycardia].
AB  - The definition of ventricular tachycardia, clear in principle as it consists of
      tachycardias arising from the ventricular mass and therefore distal to the
      bifurcation of the His bundle, is not as simple on clinical practice. When the
      QRS complexes are wide, the rate of the arrhythmia and its active or passive
      characteristics are not so clear-cut. The number of beats justifying the term
      tachycardia, the classification as simple or complex, become affairs of
      conventions, which may change with the evolution of concepts and improved
      understanding of the electrophysiological mechanisms. A certain flexibility in
      the usage of terminology should follow the evolution of ideas.

PMID- 8267497
TI  - [Mechanisms of ventricular tachycardia].
AB  - There are three fundamental mechanisms of ventricular tachycardia (VT) reentry,
      abnormal automaticity and triggered activity (TA) related to early or late after
      potentials. Reentry is certainly the mechanism of branch to branch and post
      infarction VT. Early TA is responsible for Torsades de Pointes. Late TA is
      possibly the cause of certain verapamil-responsive VT but calcium-dependent
      reentry cannot be excluded. Abnormal automaticity or late TA may also play a role
      in catecholamine-induced VT. The development of drugs specific for the mechanism
      confronted with the results of programmed stimulation and mapping should improve
      the understanding of the mechanism of VT in each individual patient and allow
      more effective and better tolerated antiarrhythmic therapy.

PMID- 8267498
TI  - [Diagnosis of ventricular tachycardia by electrocardiography].
AB  - In monomorphic wide QRS complex tachycardia, it is important to differentiate
      ventricular tachycardia from supraventricular tachycardia with aberration or
      preexcitation both from the prognostic and therapeutic view points.
      Atrioventricular dissociation with fusion complexes allows diagnosis of
      ventricular tachycardia but the negative predictive value of these criteria is
      low. Extreme QRS axis deviation, concordant morphological criteria in leads V1-V2
      and V6 and analysis of the RS complexes in the precordial leads, nearly always
      enable supraventricular tachycardia with aberration. The distinction with other
      causes of wide QRS complex tachycardias (supraventricular tachycardia with
      preexcitation or with non-systematized intraventricular conduction defects) is
      much more difficult in the absence of a reference recording and depends more on
      the clinical context than ECG analysis.

PMID- 8267499
TI  - [Non invasive exploration of ventricular tachycardia].
AB  - Complementary investigation of ventricular tachycardia requires the use of non
      invasive techniques before treatment, before considering other methods. Non
      invasive investigations are usually complementary. Signal averaged
      electrocardiography allows detection of after potentials, a sign of a reentry
      circuit. Twenty-four hour Holter monitoring and exercise testing may reveal
      ventricular arrhythmias which could induce tachycardia. They may also show a
      "trigger" of tachycardia such as the catecholamine factor which is particularly
      sensitive to exercise testing and Holter monitoring. The latter investigation
      also informs on the variability of the heart rate, the disappearance of which is
      an argument in favour of the risk of sudden death. Holter recording and exercise
      testing should also be repeated after starting antiarrhythmic treatment to
      control the efficiency and detect possible proarrhythmogenic effects. The problem
      with these investigations is that they lack sensitivity as they are sometimes
      normal in patients with documented VT or lack specificity, ventricular
      arrhythmias being common and often without clinical significance.

PMID- 8267500
TI  - [Electrophysiological evaluation of ventricular tachycardia].
AB  - The ability to induce and terminate ventricular tachycardia reproducibly by
      programmed stimulation has led to the development of electrophysiological
      investigations for the management of patients suffering from spontaneous
      arrhythmias. The investigation consists in introducing several multipolar
      catheter electrodes under local anaesthesia which are then positioned in contact
      with the endocardium in several regions of the heart. There is no consensus as to
      an ideal stimulation protocol for these patients but the basic principle is the
      introduction of one or several ventricular extrasystoles every 8 beats in sinus
      rhythm or during a controlled ventricular paced rhythm. At present, the major
      indication is rarely diagnostic in the presence of wide QRS complex tachycardias
      difficult to analyse by electrocardiography. On the other hand,
      electrophysiological investigations are highly recommended in cases of
      unexplained syncope in patients with documented or suspected heart disease, in
      symptomatic patients with intraventricular conduction defects in whom ventricular
      arrhythmias are suspected as the cause of symptoms or after cardiac arrest
      without transmural infarction or, for many teams, after the 48th hour of
      transmural infarction. Electrophysiological investigations are also justified in
      patients in whom surgical or catheter ablation of an arrhythmogenic focus is
      planned because of resistance to antiarrhythmic drug therapy. Evaluation of the
      efficacy of antiarrhythmic drugs by repeated investigations is common in the
      United States but is not so widely accepted in Europe.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8267501
TI  - [Ventricular tachycardia of ischemic cardiomyopathies].
AB  - Ventricular tachycardia in patients with ischemic heart disease are almost always
      observed after myocardial infarction without preservation of the border zone
      (thrombolysis or early angioplasty). Monomorphic tachycardias are related to
      permanent electrophysiological substrate with a zone of slow conduction. This may
      be affected by initiating factors such as extrasystoles, especially with
      alternating long and short cycles, and the sympathetic nervous system before the
      appearance of clinical tachycardia. Cardiac mortality is mainly due to sudden
      death after an initial episode of sustained monomorphic ventricular tachycardia.
      The prognostic value of left ventricular function as assessed by the ejection
      fraction is essential: the 5-year mortality is 30% if LVEF is > 0.3 compared with
      51% if LVEF is < 0.3 (p < 0.01). On the other hand, the frequency of spontaneous
      VT and VT induced by programmed stimulation does not affect the prognosis. The
      mortality after an initial episode of syncopal tachycardia is greater than after
      a well tolerated tachycardia. This is why the clinical history of the patient is
      essential to guide management. The persistence of inducible VT despite
      antiarrhythmic therapy increases the mortality; it is therefore important to find
      a drug which prevents induction VT. The patient is then classified as
      "responder". The number of "responders" patients, however, is low when the
      ejection fraction is < or = 0.30. The choice of treatment seems important when
      the ejection fraction is < or = 0.30: in this case, patients receiving Class I
      antiarrhythmics have a higher mortality and those taking betablockers have a
      reduced mortality. After polymorphic VT, if VT or VF is inducible, the risk of
      mortality is very high.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267502
TI  - [Ventricular tachycardia of dilated cardiomyopathies].
AB  - Patients with dilated cardiomyopathy often have unsustained VT (15 to 60% of
      cases) but sustained VT is much less common (0 to 10% of cases). The predictive
      value of sudden death of VT in Holter monitoring is not unanimously accepted.
      Therefore, it appears that, in patients with non-symptomatic VT, it is the degree
      of left ventricular dysfunction which is the best predictive factor of mortality
      because Holter monitoring, signal averaged ECG and programmed stimulation have a
      low positive predictive value although their cumulated negative predictive value
      seems to be very good. Programmed ventricular stimulation should be proposed to
      patients considered to be at high risk of sudden death, presenting with
      symptomatic unsustained VT or sustained VT. Approximately 3 out of 4 of these
      arrhythmias will be inducible and benefit from this method for orientating the
      choice of treatment. In these high risk subjects about 1 in 3 will be
      satisfactorily protected by antiarrhythmic drug therapy: non-inducible patients
      from the outset and those remaining inducible despite antiarrhythmic therapy
      remain at high risk of sudden death. This group of patients probably represents
      the best indication of implantable cardioverter defibrillators.

PMID- 8267503
TI  - [Sustained monomorphic ventricular tachycardia in non ischemic heart diseases].
AB  - Sustained ventricular tachycardia in the absence of coronary artery disease is
      mainly observed in diffuse left ventricular cardiomyopathy especially dilated but
      sometimes hypertrophic, and in right sided cardiomyopathies such as ventricular
      dysplasia, more difficult to diagnose. More rarely, other localised
      abnormalities, mitral valve prolapse, cardiac tumour and idiopathic aneurysm, may
      give rise to this arrhythmia. Irrespective of the case, sustained ventricular
      tachycardia carries a poor prognosis during the most advanced stages of a
      myocardial disease. The therapeutic strategy remains the same as that of other
      cases of sustained ventricular tachycardia, drug therapy generally orientated by
      the results of programmed ventricular stimulation with the exception of Class I
      antiarrhythmics when the ejection fraction is under 30%, and non-pharmacological
      methods when drug therapy fails.

PMID- 8267504
TI  - [Drug-induced ventricular tachycardia].
AB  - Certain drugs can induce ventricular tachycardia (VT) by creating reentry,
      ventricular after potentials or exaggerating the slope of phase 4. These may or
      may not be symptomatic, sustained or non-sustained and have variable ECG
      appearances: monomorphic or polymorphic, bidirectional, torsades de pointes. They
      risk degenerating into ventricular flutter of fibrillation and have been held
      responsible for the increased mortality observed unexpectedly in some long-term
      treatments. The drugs responsible are mainly those used in cardiology, probably
      due to predisposing circumstances (cardiomegaly, cardiac failure, previous severe
      ventricular arrhythmias, therapeutic associations, metabolic abnormalities).
      These include primarily the antiarrhythmic drugs (IA, IC, sotalol and bepridil),
      digitalis, sympathomimetics and phosphodiesterase inhibitors. These complications
      may be toxic or idiosyncratic, in patients with or without cardiac disease, and
      may also occur with other drugs: vasodilators and anti-anginal drugs
      (lidoflazine, vincamine, fenoxedil), psychotropic agents (phenothiazine and
      imipramine), antimitotics, antimalarials (chloroquine) or antibiotics
      (erythromycin, pentamidine). The prognosis is severe and the treatment is often
      difficult which makes prevention, helped by repeated surface ECG (or Holter
      monitoring), very important with careful assessment of patients at risk.

PMID- 8267505
TI  - [Torsades de pointes].
AB  - Torsades de pointes are defined and characterised by specific, polymorphic but
      organised ventricular activation on the surface electrocardiogram. They
      constitute episodes of rapid tachycardia which are usually short lasting and
      terminate spontaneously. However, they may recur and persist, leading to syncope
      or sudden death. They occur typically in cases with abnormalities of ventricular
      repolarisation with prolongation of the QTU interval and variable deformations of
      the TU waves. The basal abnormalities may be modest or intermittent. A bigeminy
      with a long coupling interval and alternating long and short cycles often precede
      the burst of arrhythmia. Abnormalities of ventricular repolarisation and torsades
      de pointes may be the result of congenital syndromes (catecholamine-dependent
      torsades) or acquired factors (pause-dependent torsades) such as paroxysmal
      bradycardia, drugs which prolong the repolarisation and potassium and magnesium
      deficiencies. The electrophysiological mechanisms comprise reentry and after
      depolarisation induced activity genetic factors causing abnormalities of the G
      proteins, potassium currents or adrenergic receptors may also play a role.
      Emergency treatment consists of intravenous magnesium salts, sometimes of
      betablockers or verapamil for maintenance therapy. The association of a potassium
      sparing drug may be useful. Cardiac pacing may be necessary. Left sympathetic
      denervation or implantation of an automatic defibrillator are exceptional
      therapeutic options in refractory congenital torsades de pointes.

PMID- 8267506
TI  - [Torsades de pointes with short coupling interval].
AB  - The authors describe a ventricular arrhythmia observed in 14 patients between
      1972 and 1991, and 9 cases in the literature. The patients were hospitalised for
      investigations of syncope related to torsades de pointes. They were characterised
      by the very short coupling interval to the initiating extrasystole (average: 245
      ms), by the young age of the patients (average: 34.6 years) and by the absence of
      overt cardiac disease. The resting electrocardiogrammes were normal, especially
      ventricular repolarisation. Some recordings showed isolated ventricular
      extrasystoles with short coupling intervals. Quite often, a family history of
      sudden death was obtained. These episodes of ventricular arrhythmia may
      degenerate to ventricular fibrillation. Pharmacological and electrophysiological
      investigations did not show any consistent characteristic electrophysiological
      behaviour. Investigations of autonomic nervous system function showed a decrease
      in global sinus rhythm variability and an increased sympathetic over
      parasympathetic activity. The clinical outcome of these patients is unpredictable
      with present methods. From a therapeutic point of view, Class I antiarrhythmics,
      betablockers and amiodarone were ineffective. Verapamil showed an
      electrocardiographic improvement by increasing the coupling interval of the
      extrasystoles and decreasing or even suppressing some repetitive forms, but
      without preventing recurrences. The indications for an implantable automatic
      defibrillator should be considered in this group of patients. These patients have
      clinical and electrocardiographic abnormalities which are sufficiently coherent
      for them to constitute a new pathological entity which the authors suggest
      calling "torsades de pointes with a short coupling interval".

PMID- 8267507
TI  - [Primary ventricular fibrillation].
AB  - In the absence of autopsy studies, the etiological diagnosis of this form of
      ventricular fibrillation (VF) depends on the exclusion of cardiac disease by all
      available invasive and non-invasive diagnostic methods. Primary VF is rare and
      affects young adults. There are few clinical markers and published
      electrophysiological data indicates that sustained ventricular tachycardia or VF
      is unlikely to be induced by programmed ventricular stimulation. The underlying
      mechanism of the arrhythmia is poorly understood. However, a possible
      arrhythmogenic substrate has been suggested in small zones of fibrosis within
      normal Purkinje tissues, as encountered in some minor forms of arrhythmogenic
      right ventricular dysplasia. Also, the role played by the autonomic nervous
      system in triggering VF seems to be particularly important. Some described cases
      resemble curiously "torsades de pointes" with a short coupling interval. The
      "cardiac" prognosis of resuscitated patients is usually good. However, arrhythmic
      recurrences are common, and, classically, antiarrhythmic drugs are usually
      ineffective. The indication for implantation of an automatic defibrillator is
      therefore justified in patients surviving primary VF. The lack of understanding
      of this condition is an argument in favour of setting up a French register of
      patients with primary VF in order to establish its clinical features.

PMID- 8267508
TI  - [Ventricular tachycardia in children].
AB  - Ventricular tachycardia (VT) in children is different to that observed in the
      adult because ischemic heart disease is exceptionally rare in this age group. The
      arrhythmia sometimes presents with cardiac failure or loss of consciousness. VT
      complicates the outcome of operated Tetralogy of Fallot, arrhythmogenic right
      ventricular dysplasia and some cardiac tumours. Cardiomyopathies are also a cause
      of VT but it must be noted that ventricular dysfunction may be the result of a
      prolonged arrhythmia and will disappear after return to sinus rhythm. Many cases
      of childhood VT occur without any patent cardiac disease even after extensive
      investigations. Some are benign with a good prognosis, such as salvoes of VT or
      sustained attacks of so-called ventricular Bouveret. Others carry a more reserved
      prognosis and require active treatment. Incessant tachycardia of the newborn is
      difficult to stop may be cured without sequellae. Torsades de pointes is
      sometimes iatrogenic complicating congenitally long QT syndromes with or without
      deafness or familial nature, and which may be likened to adrenergic VT.
      Amiodarone and betablockers are the best antiarrhythmic agents. Investigations
      with a diagnostic or therapeutic objective are easier in older children but these
      techniques, whilst not being systematic, do not exclude the very young children.
      Ablation techniques progress and the limited indications of surgery and
      implantable defibrillators have to be considered case by case.

PMID- 8267509
TI  - [Pharmacological treatment of ventricular tachycardia].
AB  - Pharmacological antiarrhythmic therapy is the treatment of first intention for
      the prevention of ventricular tachycardia (VT). In sustained VT,
      electrophysiological investigations without treatment enable the induction of VT,
      the demonstration of its reproducibility, the confirmation of diagnosis (if
      necessary), the determination of its mechanism and the choice of treatment. In an
      effort to standardise the technique, a minimum acceptable protocol of
      stimulations was agreed upon: at least 2 cycles (600 milliseconds and 400
      milliseconds) and 3 extrastimuli (S2, S3, S4). The percentage of inducibility
      (sensitivity) depends on the underlying heart disease and is of the order of 90
      95% in coronary artery disease with a history of infarction. Serial
      electrophysiological studies show non-inducibility of VT with treatment in 20-60%
      of cases. This result is influenced by the ejection fraction, the type of
      ventricular arrhythmia (fibrillation or tachycardia) and the antiarrhythmic agent
      tested. A Class IA, then a Class IC antiarrhythmics or sotalol (if the ejection
      fraction is over 40%) are evaluated by this technique. Empiric therapy has no
      place in the management of malignant poorly tolerated arrhythmias. In recurrent,
      well tolerated arrhythmias which are non-inducible, treatment may be guided by
      the results of Holter monitoring, providing the patient has a sufficient number
      of extrasystoles. Exercise stress tests may be useful in effort or catecholamine
      induced tachycardias. There is no consensus about the management of non-sustained
      VT. When these arrhythmias are associated with syncope or cardiac arrest,
      programmed ventricular stimulation seems indicated. The choice of antiarrhythmic
      drugs and their results are reviewed.

PMID- 8267510
TI  - [Non-pharmacological treatment of ventricular tachycardia (anti-arrhythmic
      surgery excluded)].
AB  - There has been real change in the treatment of VT in recent years including the
      promotion of non-medical methods. In the large group of non-responders to medical
      therapy, only a minority offers possibilities of radical surgical treatment of
      VT. In the others, two options remain: ablative methods and implantable automatic
      cardioverter defibrillators. The destruction of foci of tachycardia by
      catheterisation necessitates prior investigation of the ventricular endocardium
      with recordings of endocardial electrograms during VT. Criteria defining the zone
      for ablation are two-fold: either the zone of earliest endocardial depolarisation
      or the exit zone (generally preceding the tachycardia QRS complexes by 20 to 30
      ms). The second is the zone of slow conduction which corresponds to the cardiac
      substrate in which the tachycardia arises. In the absence of satisfactory
      mapping, localisation of the ablation target may be performed by stimulating the
      endocardium at different points with the aim of reproducing the tachycardia QRS
      complexes. Two types of physical agents have been used for ablation: high energy
      electric shocks and, at present, radiofrequency currents. Complications of the
      procedure are rare: thromboembolism, cardiac rupture, cardiogenic shock in
      patients with initially poor hemodynamic conditions. Prevention of VT is obtained
      in over half the cases providing complementary antiarrhythmic therapy is
      prescribed. The other alternative is the implantable automatic defibrillator
      which is tending to take over the leading role in non-pharmacological treatment
      of VT. At first, these devices were exclusively defibrillators but nowadays they
      have anti-tachycardia functions which widen the indications to include subjects
      with sustained VT even in the absence of cardiac arrest.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8267511
TI  - [Surgical treatment of ventricular tachycardia].
AB  - Refractory ventricular tachycardia, resistant to antiarrhythmic drug therapy
      either because of inefficacy unwanted secondary effects or failure to comply with
      treatment, is not rare in the chronic phase of myocardial infarction. These
      considerations reinforce the value of curative therapeutic options, especially
      those related to antiarrhythmic surgery in these patients. Surgery is usually
      reserved for those with a ventricular aneurysm where the exclusion of
      arrhythmogenic zones may be performed with the scalpel, a cryoprobe, laser ...
      Procedures guided by peroperative endo end epicardial mapping, if possible
      simultaneous with computerised assistance, are more effective than procedures
      relying only on visual guiding. The clinical success rate is about 90% and the
      operative mortality tends to decrease (5 to 6%) with successive improvements to
      surgical technique. These satisfactory results show the reliability of this
      therapeutic approach applied to patients exposed to malignant arrhythmias.

PMID- 8267512
TI  - [Molecular modelling studies on hormone binding regulation by estrogen
      receptors].

PMID- 8267513
TI  - [Hormone antagonists: discovery of steroid hormones for specific cancer therapy].

PMID- 8267514
TI  - New NO-donors with antithrombotic and vasodilating activities, II: 3-alkyl-N
      nitroso-5-sydnone imines.
AB  - Fifteen 3-alkyl-, four 3-cycloalkyl-N-nitroso-5-sydnone imines and five 3-alkyl-N
      nitro-5-sydnone imines were synthesized and their ability to inhibit platelet
      aggregation induced by collagen (Born-test) was studied in vitro. Dependent on
      the chemical structure, the IC50-values for the inhibition of platelet
      aggregation were in the range of 0.2-140 mumol/L. It is suggested that this scale
      reflects different binding properties of the nitrosimines with respect to the
      platelet membrane. Highest activities were observed for the 3-hexyl (2f) and the
      3-cyclohexyl (2p) derivative. Three nitrimines (3e, 3f, 3i) also showed IC50
      values below 10 mumol/L. For the nitrosimines 2a, 2f, and 2m antithrombotic
      activity was demonstrated in vivo. They inhibited laser induced arterial
      thrombosis in anesthetized rats up to 70% two h after oral administration. In
      conscious renal-hypertensive dogs, the decrease in systolic blood pressure and
      left ventricular enddiastolic pressure suggests an antianginal activity of the
      compound 2a similar to that of molsidomine (M). The smoother onset and the longer
      duration of action of the new compound as compared to M could be a significant
      advantage of 2a in the therapy of angina pectoris.

PMID- 8267515
TI  - Biotransformation of benzamidine and benzamidoxime in vivo.
AB  - After administration of benzamidine (1) or benzamidoxime (2), respectively, to
      rats and rabbits, plasma from rats and rabbits as well as urine from rats were
      examined for the presence of benzamidoxime (2) or benzamidine (1). Some of the
      samples were worked-up directly and the others after enzymatic pretreatment with
      beta-glucuronidase or arylsulfatase, respectively. HPLC analysis was employed for
      the detection of the metabolites. After administration of 1, an in vivo N
      hydroxylation of an amidine to an amidoxime was demonstrated for the first time.
      The metabolite 2 could only be detected after enzymatic cleavage of the
      glucuronide or sulfate, respectively, and only in plasma at a low concentration.
      After administration of benzamidoxime (2), on the other hand, benzamidine (1) was
      detected in very high concentrations in all biological samples. Benzamidine was
      present in the free state but indications for glucuronidization and sulfatation
      were also detectable. These investigations suggest that the benzamidoxime (2)
      formed by an in vivo N-hydroxylation undergoes ready retro-reduction but that
      further transformations of the metabolite 2, such as conjugation to a glucuronide
      or a sulfate, respectively, prevent complete back reaction. Furthermore,
      benzamide (3) could be detected as a transformation product in urine after
      administration of either 1 or 2.

PMID- 8267516
TI  - [Indoles. 9. 4-Arylated tetrahydro-beta-carbolines--synthesis and first
      pharmacologic data].
AB  - Two different routes lead to the 4-arylated tetrahydro-beta-carbolines 5, 11, 12.
      One includes Pictet-Spengler cyclization of tryptamines 9, the other follows our
      "lactone-route", starting with 1 via 2-4. In a first pharmacological screening
      some target compounds show significant affinity at the 5-HT2-receptor but no or
      only low affinity to other binding sites.

PMID- 8267517
TI  - Effects of oxygen radicals, hydrogen peroxide and water-soluble singlet oxygen
      carriers on 5- and 12-lipoxygenase.
AB  - Inhibition of 5-lipoxygenase from bovine polymorphonuclear leukocytes and 12
      lipoxygenase from bovine platelets by active oxygen species has been studied.
      Oxygen radicals and hydrogen peroxide markedly inhibited 12-lipoxygenase, whereas
      5-lipoxygenase activity was only moderately influenced. Singlet oxygen liberated
      from water-soluble naphthalene endoperoxides was without effect.

PMID- 8267518
TI  - [Synthesis of homochiral 5,9-epoxybenzocyclooctenes with amino substitutents:
      relationship between structure and CNS activity].
AB  - This paper deals with the synthesis and psychopharmacological effects of
      variations of the sedative and analgesic tricyclic amines 3a and 3b: Starting
      with the homochiral ketone 4 the amines 5 (primary amino group in equatorial
      position), 7 (axially oriented dimethylamino group), 9 (additional phenyl residue
      in position 7), 13b, and 14b (equatorially and axially arranged
      dimethylaminomethyl group) and 23 and 24 (axial amino group shifted to position
      9) are prepared. BBr3 cleaves the phenolic ethers of the secondary amine (+/-)-3a
      to yield the aminodiphenol (+/-)-10. -Keeping mice under observation for
      behavioral anomalies (Irwin screen) and analgesic activity (writhing test) shows,
      that the amines 5, 7, 9, (+/-)-10, 13b, 14b, and 23 do not reach the sedative and
      analgesic effects of the amines 3a and 3b, described by us.

PMID- 8267519
TI  - Synthesis and molluscicidal activity of new derivatives of 1-(hydroxy/substituted
      phenyl)-3-arylpropenones.
AB  - Several 1-(hydroxy/substituted phenyl)propenones were tested as molluscicidal
      agents among which the 1-(2-hydroxy/substituted phenyl)-3-(2-furyl)propenones 1a
      c show the most promising results. In an attempt to improve their activity, new
      dihydropyrazolo[1,5-c][1,3]benzoxazines, their thio and their dehydrogenated
      derivatives were prepared. The pyrazolo[1,5-c][1,3]benzoxazines 4a,b were
      hydrolyzed affording the 3-(2-furyl)-5-(2-hydroxy/substituted phenyl) pyrazoles
      8a,b. The hydroxyimino derivatives 10a-c were synthesized together with their
      corresponding isoxazole derivatives 11a-c. -Molluscicidal assay indicated that
      the oximes 10b,c, the isoxazole 11b, the pyrazole 8b, and its N-carbamoyl
      derivative 9b are most effective. They have in common the conjugated system shown
      in Fig. 1 which is presumably the active core.

PMID- 8267520
TI  - [The 43rd General Meeting of the Japanese Society of Allergology. Yokomama,
      Japan. October 23-25, 1993. Abstracts].

PMID- 8267521
TI  - Changes in the levels of several endogenous opioid peptides in dog cerebrospinal
      fluid following morphine administration.
AB  - The cisterna magna of dogs anesthetized with sodium Surital was fitted with a
      cannula, and cerebrospinal fluid (CSF) was withdrawn before (control) and one
      hour after the s.c. injection of 10 mg/kg of morphine sulfate (morphine). The CSF
      from control and morphine-treated dogs was purified initially by gel filtration.
      Each fraction was submitted to opiate bioassay procedures, followed by high
      performance liquid chromatography (HPLC) purification on a mu-Bondapak C18
      column. Two of the CSF fractions from HPLC purification showed greater opiate
      like activity after morphine treatment than that in controls. One fraction
      contained morphine, the other an unknown peptide. This latter fraction produced a
      dose-dependent effect in the mouse tail-flick test. This fraction did not show
      radioimmunoreactivity to methionine (met)- or leucine (leu)-enkephalins, but
      showed a small amount of reactivity to beta-endorphin and dynorphin (1-13).
      Further purification of this fraction by HPLC yielded a fraction with five peaks,
      which upon amino acid analysis were found to contain small peptides. Met- and Leu
      enkephalins, beta-endorphin and dynorphin (1-13)-like immunoreactivity in the
      fraction in which the respective standard was eluted by HPLC was significantly
      increased after a single administration of morphine. Based on these results, it
      is suggested that morphine at an antinociceptive dose causes the release of
      endogenous opioid peptides and may also stimulate the biosynthesis of their
      precursor molecules, pre-pro-opiomelanocortin, pre-pro-enkephalin A and pre-pro
      enkephalin B.

PMID- 8267522
TI  - [Contribution of the ALDH2 and CYP2E1 genes to flushing response and drinking
      patterns in Japanese healthy volunteers].
AB  - Relationship between genotypes of the loci for ALDH2 and CYP2E1 and the flushing
      response as well as drinking pattern were investigated among 31 Japanese healthy
      persons. In 14 persons who showed flushing symptom and whose ALDH2 genotype was
      heterozygote (ALDH2*1/ALDH2*2), 6 persons whose CYP2E1 genotype was mutant
      homozygote or heterozygote (C2/C2 or C1/C2), reported to drink more frequently
      and their alcohol consumption was higher than that of C1/C1 carriers. However, 2
      subjects possessing C2 allele in 3 persons carrying ALDH2 homozygous genotype
      showed very low alcohol consumption. It is concluded that a person heterozygous
      for ALDH2 and either mutant homozygous or heterozygous for CYP2E1 may become able
      to drink more alcohol, if his drinking pattern grows more frequent.

PMID- 8267523
TI  - [Genetic and epidemiologic studies on alcoholic liver diseases].
AB  - Polymorphic alleles of several genes such as ADH2, ALDH2, ApoB100, GST1, GST3 and
      ALAD were investigated from the aspect of the relationship with alcohol related
      diseases. DNAs were prepared from whole blood samples of 84 healthy controls
      (male), 70 patients (male) with alcohol related diseases and 87 patients (male)
      with non-alcoholic diseases. PCR technique was used for the detection of GST1
      showed a good correlation to alcoholic liver diseases. The patients with
      alcoholic liver diseases had a higher frequency of ALDH2*1 than the healthy
      controls (p < 0.005). The frequencies of GST1 gene deletion in the samples were
      as follows: Healthy controls; 47.6%, alcoholic liver diseases (fibrosis: 75%,
      cirrhosis: 65.5%, hepatoma: 75%) and non-alcoholic liver diseases: 54%. The data
      indicated that the patients with alcoholic liver diseases had a significantly
      higher frequency of gene deletion than the healthy controls (p < 0.005). In
      addition, homozygote of ALAD1 allele detected by MpsI-RFLP showed a good
      correlation to alcoholic liver diseases. Thus, the genetic polymorphism of ALDH2,
      GST1 gene deletion and ALAD can be applied widely for the study of genetic
      association with alcoholic liver diseases.

PMID- 8267524
TI  - Risk of noise-induced hearing loss following exposure to Chinese firecrackers.
AB  - Firecrackers produce sound impulses reaching peak levels measured at the ear
      sometimes in excess of 160 dB when fired at 2 m distance. These sound levels are
      potentially hazardous to the ear. Current damage risk criteria for impulse sounds
      show that for 10 impulses the peak levels should not exceed 149 dB(lin,peak) at
      the ear. The A-weighted, impulse (integration time 35 ms) levels should not
      exceed 125 dB(A,imp) at the ear for 10 impulses.

PMID- 8267525
TI  - Effects of hyperthermia on the auditory-evoked brainstem responses in mice.
AB  - This study investigated the effects of increased body temperature on the
      latencies and amplitudes of the auditory-evoked brainstem response (ABR) in mice.
      Six eleven-week-old male CBA/CaJ mice were anesthetized with pentobarbital and
      screened for normal hearing. Hyperthermia was induced by placing the animal in a
      thermostatically controlled chamber; a thermistor connected to a digital
      thermometer measured the rectal temperature. ABRs were evoked with broad-band
      clicks presented at repetition rates of 21.1/s and 61.1/s. The latencies and
      amplitudes of waves I-V were measured at 1-degree and/or 0.5-degree intervals
      between 37 and 42 degrees C. Temperature elevation between 37 and 41 degrees C
      shortened the latencies of all the ABR waves, the effect being linear and
      cumulative across the time window. Change in this trend occurred between 41 and
      42 degrees C, whereby the latencies of all the waves stabilized or showed minimal
      prolongation. Amplitudes of the most robust waves I and II showed a trend similar
      to the latencies, whereas the later waves showed erratic and uninterpretable
      changes. These findings in the mouse may be indicative of the physiological limit
      of thermal tolerance and as such may be regarded as a premonitory signal of
      permanent damage.

PMID- 8267526
TI  - Effects of hypobaric hypoxia on the middle-latency and steady-state auditory
      evoked potentials.
AB  - The aim of the present paper was the investigation of middle-latency responses
      (MLRs) and steady-state responses (SSRs) during and after a 30-min exposure to
      hypobaric hypoxia (5182 m above sea level). The test was performed in a hypobaric
      chamber on 8 male audiologically normal volunteers. The auditory stimulus (500-Hz
      tone burst), delivered at rates of 10 and 40/s for MLRs and SSRs, respectively,
      was recalibrated in the hypobaric condition because of the reduced air density.
      Absolute latencies of waves Na and Pa and their interpeak amplitude were the MLR
      parameters investigated; for the SSRs, the first positive wave (P1) absolute
      latency and the interpeak amplitude between P1 and the first negative wave (N1)
      were considered. The results showed an absence of statistically significant
      modification of the MLRs. On the contrary, the SSRs showed a significant (p <
      0.025) latency increase during hypoxia, with an immediate recovery upon return to
      ground level. No significant changes of SSR amplitudes were observed. One
      possible data interpretation is related to the higher stimulation rate adopted
      for the SSRs; a second possibility could be a different electrogenesis between
      MLRs and SSRs.

PMID- 8267527
TI  - The impact of acquired hearing impairment on intimate relationships: implications
      for rehabilitation.
AB  - Hearing disabilities, due to their interactive nature, strongly affect intimate
      relationships. This paper reviews the literature on this dimension of the
      experience of hearing impairment. The effects of progressive hearing loss and of
      the coping process within the couple are examined borrowing concepts from
      symbolic interaction theory. A summary of the interactive dimensions of the
      effects of hearing impairment on the couple is drawn from the relevant studies.
      Specific needs have been identified for each partner in terms of information,
      support and communication facilitation. Implications are drawn for the
      audiological rehabilitation of hearing-impaired adults.

PMID- 8267528
TI  - The responsibility of established colleges to the developing world.

PMID- 8267529
TI  - The responsibility of the Royal Australasian College of Surgeons in Asia.

PMID- 8267530
TI  - ASPECT in the Pacific: walking the aid tightrope. Australian South Pacific Eye
      Consultant Teams.
AB  - The Australian South Pacific Eye Consultant Teams (ASPECT) have been functioning
      since 1985, building on previous experience with the provision of eye health
      services in the independent countries of the South Pacific. The key issues in the
      provision of aid to developing countries are the desires of those countries to
      receive aid, the delivery of care that is pertinent to local conditions and the
      training which can be delivered to local health care workers so that aid
      programmes will eventually make themselves redundant.

PMID- 8267531
TI  - The achievements of Interplast.

PMID- 8267532
TI  - A state-wide campaign for the early detection of cancer in Sabah.
AB  - The Medical Department of Sabah, in collaboration with various governmental and
      non-governmental agencies and 'Surgeons International' conducted a state-wide
      campaign for the 'Early Detection of Cancer' over a period of 3 months from July
      1992. The purpose of the campaign was to educate the population about the early
      signs and symptoms of common cancers, to remove the myth that cancer was
      incurable and to impress on the public the need to detect cancer early for a
      possible cure and a better prognosis.

PMID- 8267533
TI  - 'Weary' Dunlop: surgeon.

PMID- 8267534
TI  - Frederic Wood Jones at school and at university.

PMID- 8267535
TI  - Around the rim: the role of surgeons in discovery and research in the Pacific
      rim. Part I. Surgeons in the Pacific: expeditioners and expedition leaders.

PMID- 8267536
TI  - The responsibility of established colleges to the developing world.

PMID- 8267537
TI  - Living related hepatic donation.

PMID- 8267538
TI  - Laparoscopy-guided percutaneous cholecystolithotomy.

PMID- 8267539
TI  - External carotid endarterectomy for amaurosis fugax in the presence of internal
      carotid artery occlusion.
AB  - Two patients with occlusion of the internal carotid artery who were experiencing
      repeated episodes of transient monocular blindness in the ipsilateral eye were
      successfully treated with external carotid endarterectomy. The mechanisms for the
      production of symptoms in the presence of an internal carotid occlusion are
      discussed, including the anatomical pathways for embolization through collaterals
      between the internal and external carotid arteries. The indications, technique
      and results of external carotid endarterectomy are reviewed.

PMID- 8267540
TI  - Splenic infarction: a complication of splenic artery aneurysm.

PMID- 8267541
TI  - Campylobacter jejuni enterocolitis causing peritonitis, ileitis and intestinal
      obstruction.
AB  - Patients with Campylobacter enterocolitis may come to laparotomy due to the
      severity of abdominal symptoms and signs, although only two patients with
      intestinal inflammation have been described and in neither was the histopathology
      documented. A case of a 52-year-old male who had a typical diarrhoeal illness of
      Campylobacter enterocolitis diagnosed on stool culture is reported. Despite
      appropriate treatment he developed signs and symptoms consistent with small
      intestinal obstruction. Laparotomy revealed peritonitis and thickened distal
      ileum with transmural inflammatory changes on histopathology. These changes were
      shown to have completely resolved at a second laparotomy, required for persistent
      obstruction due to adhesions. Recurrent adhesions culminated in a third
      laparotomy. The clinical, operative and histopathological findings may be
      confused with Crohn's disease.

PMID- 8267542
TI  - Primary prostatic lymphoma: a rare prostatic malignancy.
AB  - Primary prostatic lymphoma is a very rare condition for which the treatment is
      ill defined. A case of this condition from Australia is reported and treatment
      recommendations reviewed.

PMID- 8267543
TI  - Internal jugular vein thrombosis following carotid endarterectomy.
AB  - Internal jugular vein thrombosis (IJVT) is an uncommon condition, which is often
      not correctly diagnosed clinically. Diagnosis is readily made by duplex scan,
      computerized tomography with contrast or magnetic resonance imaging. A case of
      IJVT following carotid endarterectomy with intra-operative retraction of the
      internal jugular vein is reported.

PMID- 8267544
TI  - Epidermoid cyst of the testis.

PMID- 8267545
TI  - Insertion of subclavian line: don't get knotted.

PMID- 8267546
TI  - Aneurysm of the median artery causing carpal tunnel syndrome.

PMID- 8267547
TI  - Fulminant amoebic colitis causing a colonic mucosal tube.

PMID- 8267548
TI  - Aneurysm of the profunda femoris artery.
AB  - A case of profunda femoris artery aneurysm is presented. It is particularly
      unusual in that it is associated with anomalous vascularity, which may be of
      interest in the repair of ruptured lesions.

PMID- 8267549
TI  - Responsibility of established colleges to the developing world: the case of
      Indonesia.

PMID- 8267550
TI  - The Royal Australasian College of Surgeons in South-East Asia and the Pacific.

PMID- 8267551
TI  - Behavior genetics in Russia.

PMID- 8267552
TI  - Some aspects of behavior genetics in Russia.

PMID- 8267553
TI  - Behavior genetic differences within and between defined human populations.
AB  - The small populations of the Caucasus offer a unique opportunity to consider
      concepts, such as heritability, which are often considered properties of a trait
      but which are really properties of a population. A comprehensive strategy is
      outlined for studying intra- and interpopulation genetic structure across a wide
      range of traits and environments. A three-way association is demonstrated between
      12 of 16 psychophysiological traits, attitude, and the t allele for PTC
      sensitivity. Differences between populations and traits are evaluated in
      theoretical terms for morphological, physiological, and psychological measures.
      While decreases in performance with inbreeding are often predicted, in these
      small, isolated populations the effects are minimal.

PMID- 8267554
TI  - Visual evoked potentials: phenotypic and genotypic variability.
AB  - Evoked potentials (EPs) provide a unique way of analyzing the relationship
      between genes and behavior. Individual differences in EPs, in response to light
      flashes of two intensities and pattern reversal, were studied in families from
      the isolated population Mechelta in the Northern Caucasus. While there were no
      age or sex differences in EP latency, or many age effects on amplitude, there
      were sex differences on the amplitude measures. Variation in the additive genetic
      determination of latency and amplitude measures is discussed. The largest
      estimates of additive genetic variation were found for the complexes of amplitude
      measures between the positive and negative waveforms.

PMID- 8267555
TI  - Differentiation of phenotypic activity and its genetic analysis in native
      populations of the Caucasus.
AB  - This study introduces a novel approach to the dissection of polygenic variation.
      First, multidimensional analysis was used to define groups within the normal
      population. Next, these groups were compared on behavioral and physiological
      measures to establish underlying mechanisms. Finally, groups were compared on a
      range of polymorphic markers to determine the extent of single-gene effects. As
      this approach was conducted using three ethnic populations, the implications of
      between-, as well as within-, population variation can be assessed.

PMID- 8267556
TI  - Neurophysiological and psychological predictors of genetic risk for
      schizophrenia.
AB  - Mathematical genetic analyses were performed on a sample of schizophrenic
      families (25 probands and 58 first-degree relatives). Heritability coefficients
      were estimated for EEG power spectrum parameters and their topography, and also
      for psychological test data on thought and speech process disorder, designed to
      assess altered selectivity in cognitive activity. Multiple regression equations
      for genetic counseling regarding the prognosis of mental illness were derived
      from the neurophysiological and psychological measures.

PMID- 8267557
TI  - Human behavioral flexibility: a psychogenetic study.
AB  - Forty-seven two-children families from Moscow were used in a study to assess
      genetic determination of behavior flexibility, which was measured by eight
      laboratory tests. Flexibility is regarded as a temperament trait. There was no
      age- or sex-specific differentiation of human behavioral flexibility. Genetic
      determination of indices was used as a criterion for construct validization of
      flexibility tests. Factor analysis produced two principal components of
      flexibility: "operational flexibility" and "afferent flexibility." The study
      showed that a considerable part of the phenotypic variability of the flexibility
      indices included in different factors is under approximately equal genetic
      control. The flexibility factors differ in their genetic determination. In the
      inheritance of the first factor the leading role belongs to the additive
      component, whereas the dominance effects are more prominent in the second factor
      of flexibility.

PMID- 8267558
TI  - Genetic aspects of animal reasoning.
AB  - This paper reviews the investigations of Prof. L. V. Krushinsky and his
      colleagues into the genetics of complex behaviors in mammals. The ability of
      animals to extrapolate the direction of a food stimulus movement was investigated
      in wild and domesticated foxes (including different fur-color mutants), wild
      brown rats, and laboratory rats and mice. Wild animals (raised in the laboratory)
      were shown to be superior to their respective domesticated forms on performance
      of the extrapolation task, especially in their scores for the first presentation,
      in which no previous experience could be used. Laboratory rats and mice
      demonstrated a low level of extrapolation performance. This means that only a few
      laboratory animals were capable of solving the task, i.e., the percentage of
      correct solutions was equivalent to chance. The brain weight selection program
      resulted in two mice strains with a 20% (90-mg) difference in brain weight.
      Ability to solve the extrapolation task was present in low-brain weight mice in
      generations 7-11 but declined with further selection. Investigation of
      extrapolation ability in mice with different chromosomal anomalies demonstrated
      that animals with Robertsonian translocations Rb(8,17) 1lem and Rb(8,17) 6Sic
      were capable of solving this task in a statistically significant majority of
      cases, while mice with fusion of other chromosomes, as well as CBA normal
      karyotype mice, performed no better than expected by chance. Mice with two types
      of partial trisomies and animals homo- and heterozygous for translocations were
      also tested.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267559
TI  - Genetic analysis of different kinds of aggressive behavior.
AB  - Various kinds of aggressive behavior such as spontaneous intermale aggression,
      predatory aggression (locust-killing behavior), and irritable (shock-induced)
      aggression were investigated in inbred strains of mice. Genotype was shown to
      affect significantly the phenotypic variety of these kinds of aggression. There
      were, however, no interstrain correlations either between intermale aggression
      and predatory behavior or between intensity of intermale, shock-induced
      aggression and locust-killing behavior. Moreover, the intermale aggression level
      (percentage of fighting mice in each strain) did not correlate with the intensity
      of fighting. It has been shown by Mendelian analysis on C57BL/6J and BALB/c
      strains that these indices of intermale aggression are under different genetic
      control. The selection of Norway rats over 20 generations for reduced fear
      induced aggressiveness toward man resulted in a decrease in irritable aggression
      and loss of an aggressive response to man. No changes in intermale and predatory
      aggression, however, were found. Hence, different kinds of aggressive behavior-
      intermale, predatory, and fear-induced aggression--seem to be controlled by
      different genetic mechanisms.

PMID- 8267560
TI  - Divergent responses to long-term stressors in rat lines selected for different
      functional states of the nervous system.
AB  - The conditioned and reflex parameters in rat lines selected for the threshold of
      excitability (a fundamental characteristics of the functional state of the
      nervous system) were estimated. This measure is based on the response of the
      tibial nerve to electrical stimulation, which gives a general indication of the
      level of excitability of other parts of the nervous system. Testing was made 1-3
      days after 15 days of daily stress caused by randomly presented pairing of light
      and unavoidable electric shock. Expression of the sensitivity to the electric
      current, and the reflex components of the behavior, depends on the genetically
      determined level of the functional state of the nervous system.

PMID- 8267561
TI  - The genetics of pheromonally mediated intermale aggression in mice: current
      status and prospects of the model.
AB  - A genetic model of pheromonally mediated aggression in laboratory male mice,
      which has been developed over the past decade, is reviewed and integrated with
      recent developments in the neurobiology of olfaction and the chemistry of
      pheromones in Mus musculus. Experimental data strongly support the possibility of
      enzymatic activation of aggression promoting and inhibiting pheromones by beta
      glucuronidase (EC 3.2.1.31). These findings introduce important questions as to
      the involvement of beta-GLU genes (Gus and Eg on chromosomes 5 and 8,
      respectively) in the determination of urine odor profiling. The discovery of two
      neuroanatomically, and functionally distinct, olfactory structures in 1975 led
      the way for direct selection of olfactory bulb relay neurons, medial amygdala
      nucleus neurons and TIDA-neurons for analysis of the genetic mechanisms involved
      in pheromonal action on aggressive and other olfactory mediated social behaviors
      in rodents.

PMID- 8267562
TI  - [Abortions in a lower Austrian sheep facility caused by Coxiella burnetii].
AB  - In a flock of sheep the causal connection between abortions and the infection
      with Coxiella burnetii is demonstrated serologically, bacteriologically and by
      pathological examination. In order to identify C. burnetii as causing agent in
      case of abortions the submission of placental parts in addition to the fetus, in
      combination with a serological control of the flock, is recommended. To check the
      seroprevalence of C. burnetii in the region concerned random blood samples of 12
      flocks were taken and analysed by CFT. At least 10 samples per herd, taken from
      animals more than 1 year old, were examined. Positive titers were found in 5.6%
      of the checked animals which originated from 6 different flocks. Health risks of
      different groups of the human population are being discussed.

PMID- 8267563
TI  - [Hormonal reactions in fattening bulls and cows during a three-week butyric acid
      exposure].
AB  - During a three-week intraruminal butyric acid resp. Na-butyrate load (1 g/kg body
      weight) we investigated the hormones insulin, cortisol, triiodothyronine (T3) and
      thyroxin (T4). Distinct effects on insulin concentration were found during the
      diurnal course which was after butyric acid application in the morning for nine
      hours depressed followed by a surplus incretion. In the morning the anteprandial
      concentrations of insulin, cortisol, T3 and T4 were not changed in the whole
      time. One cow was ill on ketosis and showed strong changes of hormones.

PMID- 8267564
TI  - [Effect of a three-week butyric acid exposure on the mineral metabolism and the
      skeletal system in cattle].
AB  - Three-week intraruminal butyric acid resp. Na-butyrate load in young fattening
      bulls, fattening bulls and cows induces different changes of mineral metabolism
      dependent on acid-base-stress. In young fattening bulls we observed typical sings
      of acidosis hyperphosphatemia and hypercalcaemia resp. hyperphosphaturia and
      hypercalciuria. In fattening bulls and cows we did not see such changes. Strong
      acidotic metabolism suppresses the activity of alkaline phosphatases
      significantly. During a three-week butyric acid load changes in bone
      mineralisation did not develop.

PMID- 8267565
TI  - [A clinical study of examples of variability and instability of fixed sections of
      canine EKGs].
AB  - Study in ECGs of a clinical collection of 45 dogs (15 dogs without heart disease
      and without sedation or anesthesia, 15 dogs with acquired and congenital heart
      disease without sedation or anesthesia, 15 dogs premedicated and anesthetised and
      all dogs except one without heart disease). Especially studied were the parts
      which are known in the ECG of the dog as variable and labile (ST-segment, ST
      segment-junction and the T-wave). In the group of premedicated and anesthetised
      dogs a curved and arched ST-segment was more often observed as in comparison to
      the other two groups. On the other hand the ECG evaluations showed that in all
      studied groups independent of the status of the heart many similar or equal
      configurations of the variable and labile parts of the ECG were observed.

PMID- 8267566
TI  - [New possibilities in oral immunoprophylaxis of newborn diarrhea in calves--a
      field study using specific egg antibodies].
AB  - To investigate the effect of oral immunoprophylaxis in diarrhea of newborn calves
      egg powder with antibodies specific to E. coli K99 (ETEC) and rotavirus were used
      in a field trial in south west Germany. Fourteen farms with a total of 105 calves
      were selected. Egg powder (21 g per day) was fed as a supplement to the regular
      diet for the first 14 days after birth. Animals of the control group received egg
      powder derived from hens not immunized with the antigens. Frequency, duration and
      severity of diarrhea, fecal dry matter and weight gain were examined in order to
      evaluate the influence of the specific egg powder. Using a Lactovac test kit
      pathogens were detected in the feces of 76.2% of the calves, with 24.7% infected
      with E. coli K99, 39.1% with rotavirus, 19.0% with coronavirus and 32.4% with
      cryptosporidia. An overall reduction in diarrhea frequency from 68.5% to 52.9%
      was observed in calves fed with specific antibodies. Animals with an E. coli K99
      infection showed a reduction from 92.3% to 30.7% and those infected exclusively
      with E. coli K99 from 83.3% to 0%. The duration of diarrhea was significantly
      reduced (42 h) in animals fed with specific antibodies in comparison to the
      control animals (60 h). With the exception of animals infected with coronavirus a
      marked reduction in the severity of diarrhea was observed in antibody treated
      calves. During the first 14 days after birth antibody treated calves showed a
      weight gain of 5.6 kg on average in comparison with 3.5 kg in the control
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267567
TI  - Two novel mutations in the vasopressin V2 receptor gene in unrelated Japanese
      kindreds with nephrogenic diabetes insipidus.
AB  - Nephrogenic diabetes insipidus (NDI) is a rare X-linked disorder exhibiting renal
      resistance to the antidiuretic action of arginine vasopressin (AVP). Recent
      elucidation of the vasopressin V2 (renal type) receptor gene structure has
      enabled us to test the hypothesis that the genetic defect in the V2 receptor is
      the likely molecular basis of NDI. By using the polymerase chain reaction (PCR)
      direct sequencing, we identified novel V2 receptor gene mutations in two
      unrelated Japanese kindreds with NDI. In the male patients of kindred A, a single
      codon deletion in one of two consecutive GTC triplets (nucleotide 832 to 837) was
      detected. This base change resulted in the loss of a valine residue in the 6th
      transmembrane domain. In the affected males of kindred B, a G to C substitution
      was found at nucleotide 428, altering codon 143 from arginine (CGT) to proline
      (CCT) in the second cytoplasmic domain. PCR-single strand conformation
      polymorphism (SSCP) analysis of family members demonstrated that the mutations
      cosegregated with clinically affected individuals and were absent in normal
      subjects. Our results suggest that different V2 receptor defects could be
      responsible for AVP resistance in individual NDI kindreds.

PMID- 8267568
TI  - Homoharringtonine induces heat protection and facilitates dissociation of heat
      shock transcription factor and heat shock element complex.
AB  - We investigated the effects of combined treatment with homoharringtonine (HHT)
      and hyperthermia on cytotoxicity and transcriptional regulation of heat shock
      genes in human colon carcinoma (HT-29) cells. The drug (100 ng/ml) which
      inhibited protein synthesis by 93% protected cells from killing at 43 degrees C.
      For example, treatment with HHT 2 hr before and during heating produced a 9-fold
      increase in survival from 3.7 x 10(-2) to 3.2 x 10(-1) after 10 hr at 43 degrees
      C. Little or no protection was observed if the drug was added only during
      heating. Interestingly, adding the drug (100 ng/ml) 2 hr before and during heat
      facilitated the dissociation of heat shock transcription factor-heat shock
      element (HSF-HSE) complex during continuous heating at 43 degrees C. These
      findings related to the literature suggest that the free pool of HSC70 is
      increased by inhibiting protein synthesis. An increase in the level of free HSC70
      may more effectively protect or repair thermolabile targets and consequently
      affect regulation of heat shock response.

PMID- 8267569
TI  - Importance of Asp1191 for tyrosine kinase activity of the insulin receptor:
      functional difference of universally conserved Asp between tyrosine kinase and c
      AMP dependent serine/threonine protein kinase.
AB  - Asp1191 of the tyrosine kinase domain in the insulin receptor is located in the
      almost perfectly conserved Ser-Asp-X-Trp motif of all tyrosine kinases, and the
      function of the motif has not been clarified. In this motif, Asp1191 is
      universally conserved in all protein kinases and corresponds to Asp220 in
      catalytic subunit of c-AMP dependent protein kinase. However, while other
      universally conserved amino acid residues are involved in catalysis, only Asp220
      is not. To determine whether this motif was not also involved in catalysis,
      Asp1191 was replaced either by alanine, asparagine, or glutamic acid and Met1192
      was replaced by valine. Asp1191-->Ala, Asn or Glu receptor lacked tyrosine kinase
      activity, while Met1192-->Val receptor showed normal kinase activity. These
      mutant receptors had no effect on insulin binding. These results suggested that
      the universally conserved Asp1191 in all protein kinases, which was not required
      for catalytic action of c-AMP dependent protein kinase, was essential for the
      tyrosine kinase activity of the insulin receptor.

PMID- 8267570
TI  - Detection of purine cytosine permease of S. cerevisiae: use of antibodies against
      a synthetic peptide corresponding to a predicted sequence in the N-terminal
      domain of the protein.
AB  - A synthetic peptide, selected in the predicted N-terminal amino-acid sequence of
      the purine cytosine permease (gene FCY2), linked to albumins proved a remarkably
      good immunogen in rabbits. In ELISA, sera reacted with the synthetic peptide and
      with specific proteins of plasma-membrane-enriched fractions of mutant
      Saccharomyces cerevisiae pAB strains (amplified FCY2 gene) with high titers and
      high avidity. Western blots of plasma membrane proteins of pAB strain probed with
      antisera showed two bands: a major (45 kDa) and minor band (50 kDa). On the
      contrary, plasma-membrane-enriched fractions of mutant S. cerevisiae pJDB strain
      (deficient in FCY2 gene) gave no signal when probed in the same conditions. These
      results demonstrate the specificity of the antisera and also suggest that the 45
      kDa and 50 kDa proteins are both products of the FCY2 gene.

PMID- 8267571
TI  - Serine phosphorylation of the secreted extracellular domain of APP.
AB  - The phosphorylation status of full-length APP (FL-APP) and secreted APP (s-APP)
      was investigated in stably transfected cells. 32P incorporation was detected in
      the mature full-length APP both in the absence and presence of phorbol ester.
      Surprisingly, 32P-phosphate was incorporated in the secreted ectodomain, and this
      was stable to treatment of the [32P]-phospho-s-APP with a large excess of PNGase
      F, suggesting that N-linked oligosaccharide sites do not account for phosphate
      incorporation. Phosphoamino acid analysis of the [32P]-phospho-s-APP resulted in
      the recovery of [32P]-phosphoserine as the preponderant species. Brefeldin A
      completely inhibited the release of [32P]-phospho s-APP, but did not inhibit the
      incorporation of 32P into the FL-APP, suggesting that phosphorylation occurs
      early in the central vacuolar pathway. It is possible that ectodomain
      phosphorylation by a novel luminal or extracellular protein kinase may play a
      role in regulating the metabolic fate of APP.

PMID- 8267572
TI  - Characterization of amyloid fibril beta-peptide in familial Alzheimer's disease
      with APP717 mutations.
AB  - Amyloid fibrils were isolated from the brain tissue of two individuals who died
      with familial Alzheimer's disease, one with the phenylalanine 717 mutation in
      amyloid precursor protein (APP) and one with the isoleucine 717 APP mutation.
      After solubilization in guanidine hydrochloride and fractionation by sieve
      chromatography, low molecular weight fractions were treated with cyanogen bromide
      to generate the beta-peptide fragment starting after the methionine at position
      35. Amino acid sequence analysis of all resultant peptides identified the peptide
      Val-Gly-Gly-Val-Val-Ile-Ala which represents residues 36-42 of the beta-amyloid
      peptide. No sequence beyond position 42 was found. These findings show that the
      amino acid substitution at position 717 is not incorporated into the amyloid
      deposits and suggests that the mutation may have metabolic affects which
      determine pathogenesis.

PMID- 8267573
TI  - Cloning of cDNA and analysis of the gene for mouse angiotensin II type 2
      receptor.
AB  - A cDNA clone encoding the mouse angiotensin receptor subtype 2 (AT2 receptor) was
      isolated from a mouse fetal cDNA library. Mouse AT2 receptor full-length cDNA
      contains a 1089-base-pair open reading frame which encodes a protein of 363 amino
      acid residues. Hydropathy analysis reveals seven putative transmembrane domains.
      Specific binding of [125I]CGP42112A was demonstrated in membranes of COS-7 cells
      transfected with the cDNA. Scatchard analysis and ligand displacement profile
      were typical of the AT2 receptor. Northern blot and reverse transcription
      polymerase chain reaction analyses demonstrated that AT2 receptor mRNA was
      expressed abundantly in fetus and in a lesser amount in adult brain. Analysis of
      the mouse AT2 receptor gene reveals that the mouse AT2 receptor locus exists as a
      single copy in the genome, and that the gene does not contain introns in the
      coding region.

PMID- 8267574
TI  - Tb(III) and Eu(III) as fluorescent probes to investigate the metal-binding sites
      of trichosanthin.
AB  - Tb(III) and Eu(III) ions were used as fluorescent probes in the study of the
      trichosanthin (TCS). The fluorescence of Tb(III) was increased considerably when
      bound to TCS to replace the Ca(II) ions. The nonradiative energy transfer from
      fluorescent tryptophan (Trp) residues to the bound Tb(III) or Eu(III) took place.
      From a Foster d-d nonradiative energy transfer mechanism, it was obtained that
      the average distance between the bound Tb(III) and the Trp residue is 1.27nm. The
      results indicate that the major groups in TCS bound to Ca(II) ions should be the
      carboxylic side groups of the glutamic acid and/or aspartic acid. The fluorescent
      quenching of Ca(II)-free TCS by adding Tb(III) or Eu(III) into TCS from which the
      Ca(II) ions had been removed was discussed as well.

PMID- 8267575
TI  - Intermolecular disulfide linkages are not required for transthyretin amyloid
      fibril formation in vitro.
AB  - The role of intermolecular disulfide linkages in transthyretin (TTR) amyloid
      fibril formation was investigated by comparing wild type TTR to Cys-10-Ala TTR
      which is incapable of disulfide formation. The Cys-10-Ala variant exhibits
      quaternary structural stability equal to the wild type protein under acidic
      denaturing conditions. Both Cys-10-Ala and wild type TTR were converted into
      amyloid fibrils by partial acid denaturation. There was no evidence of
      intermolecular disulfide formation in the case of wild type amyloid fibrils.
      These results are inconsistent with a recently proposed model stressing the
      importance of intermolecular disulfide linkages in TTR amyloid fibril formation,
      but are consistent with a model relying on noncovalent quaternary contacts made
      possible through an acid-mediated conformational change.

PMID- 8267576
TI  - Intracellular expression of anti-p21ras single chain Fv fragments inhibits
      meiotic maturation of xenopus oocytes.
AB  - The recombinant variable regions of the monoclonal antibody Y13-259, directed
      against the p21ras protein, have been engineered for expression as intracellular
      single chain Fv fragments. The activity of the plasmid was confirmed by in vitro
      and in vivo translation of mRNA showing that the intracellularly expressed single
      chain fragments are stably and efficiently expressed as cytosolic proteins. The
      expression of the anti-p21ras single chain antibodies in the cytoplasm of Xenopus
      laevis oocytes leads to the inhibition of the insulin-induced meiotic maturation.
      This finding represents the first successful application of the strategy of
      intracellular antibodies to block a complex biological process in the cytosol of
      vertebrate cells.

PMID- 8267577
TI  - Benzo(a)pyrene hydroxylase activity in yeast is mediated by P450 other than
      sterol 14 alpha-demethylase.
AB  - Benzo(a)pyrene hydroxylation has been observed in Saccharomyces cerevisiae and
      the role of sterol 14 alpha-demethylase (CYP51A1) in this activity has been
      examined by using a strain which contains a gene disruption of CYP51A1. This
      strain still contained P450 protein(s) with a Soret absorption maximum at 448nm
      in reduced carbon monoxide difference spectra of the microsomal fraction. On
      addition of benzo(a)pyrene to this microsomal extract a typical Type I substrate
      binding spectrum was obtained and was also observed for the isogenic sister
      strain containing no CYP51A1 gene disruption. Microsomal extracts of both strains
      had equivalent activity in the aryl hydrocarbon hydroxylase assay. These results
      indicate a yeast benzo(a)pyrene hydroxylase activity distinct from sterol 14
      alpha-demethylase P450.

PMID- 8267578
TI  - Preference for aromatic substitutions at tryptophan-120, which is highly
      conserved and a potential mediator of electron transfer in cytochrome P450 2C2.
AB  - A proposal that tryptophan-120 of P450 2C2 might mediate electron transfer has
      been tested by substitution of a series of aliphatic and aromatic residues at
      this position. Activity in transfected COS1 cells expressing enzymes substituted
      with the aromatic residues, tyrosine, phenylalanine, and histidine, was 25% to
      60% of wild type. Activities in enzymes containing serine, arginine, or aliphatic
      amino acid substitutions were less than 10%, except for alanine (25%). Alanine is
      the only naturally occurring substitution for tryptophan at this position in
      mammalian cytochromes P450 and is present in the electron pathway proposed on the
      basis of the crystal structure of cytochrome c and cytochrome c peroxidase. The
      preference for aromatic residues or the small aliphatic amino acid, alanine, at
      position 120 is consistent with a role for this tryptophan in electron transfer.

PMID- 8267579
TI  - The ligand binding signatures of the rat AT1A, AT1B and the human AT1 receptors
      are essentially identical.
AB  - The objective of this study was to determine whether the three isoforms of
      recombinant Ang II receptors (rAT1A, rAT1B and hAT1), stably and individually
      expressed in CHO cells, could be pharmacologically distinguished by their ligand
      binding signatures. Competition studies were performed to characterize the
      inhibition of [125I]Ang II binding to each of the cell membrane preparations by
      an extensive series of peptide and nonpeptide Ang II analogs. Scatchard plot
      analyses revealed the following binding characteristics:rAT1A-Kd = 1.27 +/- 0.14
      nM; rAT1B- Site 1:Kd = 0.56 +/- 0.11 nM, Site 2: Kd = 126 +/- 23 nM; and hAT1
      Site 1:Kd = 1.06 +/- 0.16 nM, Site 2: Kd = 257 +/- 55 nM. The binding of
      [125I]Ang II in the three preparations was similarly sensitive to inhibition by
      GTP gamma S. The ligand binding signatures of the three receptor isoforms are
      essentially the same and are illustrated by the affinity and order of potency of
      the following ligands: L-158,809 > or = Sar1, Ile8Ang II > saralasin Ang II > or
      = Ang III > EXP581 > EXP3174 > losartan > or = EXP811 > GR117,289c > EXP6803 >
      DuP 532 > Ang I >> PD123177. In conclusion, the two rat AT1 receptor isoforms are
      pharmacologically indistinguishable from each other and from that of the human.

PMID- 8267580
TI  - Exorbitantly enhanced protein gyration and erroneous membrane modification
      programs in spermatozoa after vasectomy: a biophysical basis for low infertility
      revival after vasectomy.
AB  - Vasectomy induces an immediate biophysical incompetence in epididymal spermatozoa
      in terms of the erroneous execution of membrane configuration processes,
      premature membrane melting and untimely protein gyration. Disturbances in the
      planned expression 'foreign proteins' and the possible 'swinging off' of these
      molecules from the membrane crystals might tease the immune system and might
      deprive the spermatozoa of the essential recognizing terminals.

PMID- 8267581
TI  - Two distinct signal transduction pathways for the activation of guinea-pig
      macrophages and neutrophils by endotoxin.
AB  - Lipopolysaccharide (LPS, endotoxin) is a major component of the outer membrane of
      gram-negative bacteria. Although it interacts with many types of cells and is
      linked to numerous events associated with sepsis and endotoxic shock, the
      mechanisms underlying these actions are poorly understood. We found that Ca
      signaling induced by endotoxin in guinea-pig neutrophils and macrophages is
      caused by cross-recognition of LPS with platelet activating factor (PAF)
      receptors. However, the synthesis of tumor necrosis factor-alpha or the priming
      effect of O2- production was not affected by PAF antagonists. Thus, at least two
      distinct pathways are involved in the actions of LPS, one via the PAF receptor,
      while the other is independent of a PAF receptor and Ca-signaling.

PMID- 8267582
TI  - Time dependent changes in biophysical properties of minK channels expressed in
      Xenopus oocytes.
AB  - Slowly activating, voltage-dependent minK channels cloned from rat kidney were
      expressed in Xenopus oocytes. The maximal conductance (gmax) through these
      channels increased from 11 microS at day two after mRNA injection to 22 microS
      after one week. This increase of gmax is presumably the result of an increase in
      the number of functional channels through protein synthesis of the oocyte.
      Concurrent with the increase of gmax the voltage needed to evoke a half-maximal
      conductance (V1/2) was shifted to more negative potentials, while the activation
      of minK channels was accelerated. These results suggest a relation between
      protein density and activation of minK channels. Twofold changes of gmax were
      also observed in oocytes expressing the Shaker related rat potassium channel
      RBK1; however, there was no relation between gmax, V1/2 and the activation
      kinetics of RBK1. These results are consistent with the hypothesis that minK
      channel-formation and activation might involve subunit assembly.

PMID- 8267583
TI  - Purified human vitamin D receptor overexpressed in E. coli and baculovirus
      systems does not bind 1,25-dihydroxyvitamin D3 hormone efficiently unless
      supplemented with a rat liver nuclear extract.
AB  - We report here that highly purified human vitamin D receptor (hVDR) derived from
      E. coli or baculovirus expression systems does not exhibit saturable, high
      affinity 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) ligand binding when these
      preparations alone are analyzed. Inclusion of rat liver nuclear extract, which
      does not itself contain detectable 1,25(OH)2D3 binding activity, is required to
      endow hVDR isolated from bacterial or insect cells with the property of high
      affinity hormone binding (Kd = 0.13-0.22 nM). This observation should facilitate
      the valid assay of 1,25(OH)2D3 binding activity and kinetics in samples of
      overexpressed hVDR. Moreover, since rat liver nuclear extract contains retinoid X
      receptors and possibly other auxiliary factors capable of forming heterodimers
      with hVDR that in turn associate with vitamin D responsive elements, we
      hypothesize that like DNA binding, 1,25(OH)2D3 binding to hVDR requires the
      cooperation of a co-receptor or some uncharacterized receptor
      activating/stabilizing factor.

PMID- 8267584
TI  - Interleukin 4 downregulates cell growth and prostaglandin release of human
      mesangial cells.
AB  - Several clinical studies have proposed that a T cell derived cytokine IL-4 is
      operative in glomerulonephritis; however, its biological activities on renal
      cells have not been investigated. To elucidate its possible role in
      glomerulonephritis, we have examined whether IL-4 has effect on cell growth and
      prostaglandins synthesis using cultured mesangial cells (MC). IL-4 dose
      dependently suppressed DNA synthesis and cell proliferation. IL-4 (10 ng/ml)
      alone did not affect prostaglandin E2 (PGE2) synthesis by mesangial cells,
      though, it inhibited IL-1 alpha- and TNF alpha-stimulated PGE2 synthesis by 48%
      and 81%, respectively. Comparable inhibition was observed on the conversion of
      exogenous arachidonic acid to PGs by IL-1-stimulated cells, suggesting IL-4 down
      regulates PG endoperoxide synthase activity. These results demonstrated that IL-4
      is antagonistic to inflammatory cytokines upon PG synthesis as well as anti
      mitogenic with MC.

PMID- 8267585
TI  - Purification and partial characterization of microsomal NADH-cytochrome b5
      reductase from higher plant Catharanthus roseus.
AB  - A simple three step procedure was used to purify microsomal NADH-cytochrome b5
      (ferricyanide) reductase to homogeneity from the higher plant C. roseus. The
      microsomal bound reductase was solubilized using zwitterionic detergent-CHAPS.
      The solubilized reductase was subjected to affinity chromatography on octylamino
      Sepharose 4B, blue 2-Sepharose CL-6B and NAD(+)-Agarose. The homogeneous enzyme
      has an apparent molecular weight of 33,000 as estimated by SDS-PAGE. The purified
      enzyme catalyzes the reduction of purified cytochrome b5 from C. roseus in the
      presence of NADH. The reductase also readily transfers electrons from NADH to
      ferricyanide (Km 56 microM), 2, 6-dichlorophenolindophenol (Km 65 microM) and
      cytochrome c via cytochrome b5 but not to menadione.

PMID- 8267586
TI  - Analysis of CA(2+)-binding S100 proteins in human heart by HPLC-electrospray mass
      spectrometry.
AB  - Calcium dependent processes are often impaired in myocardial dysfunctions and
      calcium-binding proteins might be involved as mediators of Ca2+ signals. Here we
      present a method to assess a footprint of the calcium-binding proteins of the
      S100 family in human heart. The S100 proteins are purified through calcium
      dependent affinity chromatography and reverse phase high-performance liquid
      chromatography and are analyzed by electrospray-ionization mass spectrometry (ESI
      MS) and liquid secondary ionization/tandem quadrupole mass spectrometry (LS
      MS/MS). In human heart we identified S100 alpha, CACY, and CAPL as the most
      abundant S100 proteins and showed that they occur as monomers and homodimers.

PMID- 8267587
TI  - Superoxide dismutase mimetic activities of metal complexes of L-2(2-pyridyl)-1
      pyrroline-5-carboxylic acid (pyrimine).
AB  - We previously isolated the strain Z-54 (Serratia marcescens O5:H1) which produces
      a reddish-violet pigment. The structure of this pigment was confirmed to be that
      of a peptide complex containing Fe2+ and L-2(2-pyridyl)-1-pyrroline-5-carboxylic
      acid (pyrimine), as a chromophore. We measured the superoxide dismutase mimetic
      activities for the pyrimine-metal complexes by xanthine oxidase/nitroblue
      tetrazolium and cytochrome c methods and found that the pyrimine-Cu2+ (2:1)
      complex shows the highest activity yet reported (IC50 = 0.11 microM) among the
      complexes tested. Pyrimine-Cu+, -Fe2+ and -Mn2+ complexes also gave relatively
      high SOD mimetic activities. ESR spectra observed for pyrimine-Cu2+ (4:1) showed
      the structure of the Cu(2+)-complex to be tetrahedral and coordinated with four
      nitrogen atoms. These results support the idea that the pyrimine-metal complexes
      might be potent SOD mimics.

PMID- 8267588
TI  - c-fos induction by stress can be mediated by the SRE.
AB  - The proto-oncogene c-fos is important in cell growth, differentiation and
      development. Several promoter elements have been identified as mediators for the
      induction of c-fos by serum, tumor promoting agents, epidermal growth factor and
      other stimuli. Stressors, including heat shock, arsenite and cadmium can induce c
      fos transcription, but a heat shock element in the c-fos promoter has not been
      described. In this report we show that the induction of c-fos by heat shock,
      arsenite and cadmium can be mediated by the serum response element. Furthermore
      we show that casein kinase II, which has been proposed to be involved in serum
      induction via the serum response element, may also be involved in heat shock,
      arsenite and cadmium induction of c-fos.

PMID- 8267589
TI  - Protein kinase C regulates IL-8 and fMLP induced cytoplasmic Ca2+ increase in
      human granulocytes by receptor modulation measurements by flow cytometry.
AB  - Changes in cytosolic free Ca2+ influence important granulocyte functions like
      chemotactic behavior, adherence to endothelia, and phagocytosis. In the following
      study we used a simple reproducible procedure involving flow cytometry in
      combination with the fluorescent dye Fluo-3 to measure Ca2+ changes in human
      granulocytes. The aim of our study was to investigate the involvement of protein
      kinase C in regulating cytosolic free Ca2+ concentrations after stimulation of
      cells with IL-8 and fMLP. Both reagents induced a 5-6 fold increase in cytosolic
      Ca2+. Experiments conducted in Ca(2+)-free media showed a minor 18-29% decrease
      in cytosolic Ca2+ response, suggesting that intracellular Ca(2+)-stores are the
      main source for Ca2+ release after fMLP or IL-8 stimulation. Activators of
      protein kinase C, phorbol myristate acetate (PMA) and 1-oleyl-2-acetyl-sn
      glycerol (OAG), inhibited cytosolic Ca(2+)-increase completely when induced by IL
      8 and by 68-82% in the case of fMLP. Staurosporine, an inhibitor of protein
      kinase C, was able to attenuate or even abolish the PMA/OAG-effect. Our results
      show that changes in cytosolic Ca2+ due to IL-8 and fMLP signalling can be
      regulated by protein kinase C in human granulocytes. This regulatory role of
      protein kinase C involves some form of receptor modulation (i.e. phosphorylation,
      internalization, shedding).

PMID- 8267590
TI  - Characterization, cloning and expression of the 67-kDA annexin from chicken
      growth plate cartilage matrix vesicles.
AB  - Analysis of a 67 kDa lipid-dependent Ca(2+)-binding protein from avian matrix
      vesicles revealed amino acid sequences homologous to mammalian annexin VI. PCR
      methods were used to identify a clone from an avian cDNA library that contained a
      full length copy of the 67-kDa annexin cDNA. This was restriction mapped,
      subcloned and sequenced. The cDNA sequence of the open reading frame showed 70
      percent identity to that of murine annexin VI; the predicted amino acid sequence,
      78 percent identity. There was no homology in the 5'- and 3'-untranslated
      regions. A plasmid was constructed that overexpresses the intact chicken 67-kDa
      matrix vesicle annexin in E. coli DH5 alpha in high yield; the physicochemical
      properties and the amino terminal sequence of the expressed protein exactly
      matched those of the native protein.

PMID- 8267591
TI  - Involvement of cytochrome P-450 in conferring chloroquine resistance to the
      malarial parasite, Plasmodium falciparum.
AB  - The higher levels of cytochrome P-450 dependent enzyme activities reported
      earlier are traced to higher levels of cytochrome P-450 (CYPIIB1/B2 like)
      messenger RNA in the chloroquine resistant than the sensitive strains. The
      messenger RNA is also induced by phenobarbitone in the sensitive strain.
      Pretreatment with phenobarbitone affords partial protection to chloroquine
      toxicity in the sensitive strain and this is not due to a differential
      accumulation of the drug.

PMID- 8267592
TI  - ADP-ribosylation of the intermediate filament protein desmin and inhibition of
      desmin assembly in vitro by muscle ADP-ribosyltransferase.
AB  - Arginine-specific mono(ADP-ribosyl)transferase purified from rabbit skeletal
      muscle catalyzes stoichiometric ADP-ribosylation of the intermediate filament
      protein, desmin. In contrast, cholera toxin catalyzes a much lower level of ADP
      ribosylation of desmin. Modification results in potent inhibition of desmin's
      ability to assemble into filaments. Phosphorylation of desmin by the catalytic
      subunit of cAMP dependent protein kinase is also inhibited by ADP-ribosylation.
      ADP-ribosylation site(s) are located within the N-terminal head domain of desmin.

PMID- 8267593
TI  - Sequential activation of two mitogen activated protein (MAP) kinase isoforms in
      rat skeletal muscle following insulin injection.
AB  - Skeletal muscle is a major target of insulin action. The possible role of MAP
      kinase activation in insulin receptor signaling in muscle was examined. After a
      48-hr fast, rats were injected intravenously with insulin or saline, muscles were
      excised after 3-20 min, homogenized, and MAP kinases were partially purified by
      ammonium sulfate precipitation and Mono Q chromatography. Activity was assayed as
      32P-incorporation into myelin basic protein. Two activity peaks were identified;
      peak I eluted with approximately 0.1 M NaCl and peak II with approximately 0.2 M
      NaCl. Three min after insulin injection the activity of peak II increased > 2
      fold, peak I was unchanged. After 10 min, the activity of peak II returned toward
      baseline, while peak I was activated approximately 3-fold. Immunoblots confirmed
      the presence of MAP kinases eluting with activity peaks I and II; the former as a
      approximately 41 kDa protein and the latter as a doublet of approximately 42 and
      approximately 44 kDa. The data suggest sequential activation of two MAP kinases
      in muscles; the isoform which activates/deactivates rapidly may represent ERK-1,
      while the more slowly responding isoform may be ERK-2.

PMID- 8267594
TI  - Evidence for enhanced expression of c-fos, c-jun, and the Ca(2+)-activated
      neutral protease in rat liver following carbon tetrachloride administration.
AB  - The effects of CCl4 on hepatic c-fos and c-jun gene expression were examined, and
      the correspondence between intermediate-early gene expression and the expression
      of the Ca(2+)-activated neutral proteinase (mu and mCANP) characterized.
      Administration of CCl4 to rats resulted in a pronounced dose- and time-dependent
      increase in c-jun and c-fos mRNA levels (approximately 8 to 17-fold) as detected
      by either Northern blot or RT-PCR analyses. The expression of mu and mCANP
      following CCl4 treatment was monitored by Northern blot analysis and mu and mCANP
      mRNA levels were found to be elevated approximately 5- to 15-fold over the time
      period of 18 to 24 h. Experiments were performed to determine whether the Fos-Jun
      heterodimeric AP-1 transcription factor complex bound the AP-1-like binding motif
      present in the mCANP gene. Gel retardation assays using hepatic nuclear extracts
      from CCl4-treated animals revealed binding of a protein to the AP-1-like motif
      present in the mCANP gene and competition and supershift assays confirmed the
      specificity of AP-1 transcription factor binding. These results show that CANP
      gene expression is enhanced in response to oxidative cellular damage and that the
      AP-1 complex may be involved in the regulation of CANP gene expression.

PMID- 8267595
TI  - Characterization of hepatocyte growth factor expressed by baculovirus.
AB  - To express recombinant hepatocyte growth factor (HGF), we cloned the cDNA by
      polymerase chain reaction. Functional recombinant HGF was expressed in insect
      cells by a baculovirus expression system. The recombinant HGF is a mixture of a
      single-chain precursor and a two-chain heterodimer. Under non-reducing
      conditions, they migrate together as a single band with MW 67 kDa on Western
      blots. Under reducing conditions, the precursor migrates at 91 kDa, alpha-chain
      at 64 kDa and beta-chain at 34 kDa. About 25% of the expressed HGF is in the
      expression medium, which does have scatter activity on HepG2 and MDCK cells and
      proliferation activity on BN CL.2 cells (a mouse hepatocytes cell line) in a dose
      dependent manner.

PMID- 8267596
TI  - Alteration of transcription factor mRNAs during the isolation and culture of rat
      hepatocytes suggests the activation of a proliferative mode underlies their de
      differentiation.
AB  - The commonly observed loss of liver specific phenotype regularly described in rat
      hepatocyte culture is typified by the loss of total cytochrome P450 (CYP) content
      and the altered abundance of CYP mRNAs. The current work shows that these changes
      are preceded by the induction of the mRNA encoding the transcription factor c-jun
      during the hepatocyte isolation procedure. Then as the hepatocytes attach to the
      substratum the induced expression of c-jun subsides and two patterns of CYP mRNA
      loss are observed. The mRNAs encoding CYPs 2C11, 2C13, 2E1, 3A1, 3A2 and 4A1
      continuously decline while CYP 1A2, 2A1/2 and 2B1/2 mRNAs are temporarily
      stabilised for 2 to 2.5 hours at a reduced level before declining further. The
      loss of CYP1A2 and 2B1/2 mRNAs parallels the loss of the mRNAs encoding the liver
      specific transcription factors C/EBP alpha and HNF-1. The early and rapid
      increase in c-jun mRNA followed by a decline in C/EBP alpha mRNA are
      characteristic of the changes in the expression of these transcription factor
      mRNAs following the stimulation of hepatocyte proliferation after partial
      hepatectomy. The finding that the rate of loss of total P450 following partial
      hepatectomy parallels that in rat hepatocyte culture suggests that the commonly
      employed hepatocyte isolation procedure "primes" the normally quiescent
      hepatocytes to enter the cell cycle and de-differentiate especially as both
      systems lose the major constitutively expressed CYP2C11 isozyme.

PMID- 8267597
TI  - Isolation of a new tautomerase monitored by the conversion of D-dopachrome to 5,6
      dihydroxyindole.
AB  - Two membrane bound enzymes which tautomerize L-dopachrome and are specific for
      the L-isomer of dopachrome have been defined in melanin forming cells. Another
      enzyme that tautomerizes D-dopachrome with concomitant decarboxylation to give
      5,6-dihydroxyindole (DHI) was found in the cytoplasm of human melanoma cells,
      human liver and in all of the organs studied in rat. The decolorization of D
      dopachrome with the formation of DHI was used in monitoring the isolation of a
      tautomerase from liver of male rats and therefore the enzyme is provisionally
      called D-dopachrome tautomerase. The molecular weight of D-dopachrome tautomerase
      monomer was approximately 12 kD and its N-terminal amino acid sequence was P-F-V
      E-L-E-T-N-L-P-A-. The Km for D-dopachrome was 1.5 mM and Vmax 0.5 mmol per min
      and mg protein.

PMID- 8267598
TI  - Identification of protein tyrosine phosphatases expressed in murine male germ
      cells.
AB  - We cloned five cDNAs encoding putative protein tyrosine phosphatases (PTPs;
      protein-tyrosine-phosphatase phosphohydrolase, EC 3.1.3.48) from the murine
      testis by using degenerate primers and the polymerase chain reaction cloning
      technique. Two of them were identical to the mouse cytoplasmic PTP and PTP-1B.
      The remaining three were likely to represent the murine counterparts of human PTP
      delta, human PTP epsilon, and rat striatum-enriched PTP. The cells expressing
      these genes were determined either by in situ hybridization histochemistry or by
      Northern blot hybridization. Moreover, Northern blot hybridization revealed that
      the transcripts of PTP-1B, mouse cytoplasmic PTP and the murine homologue of
      human PTP delta were quantitatively and/or structurally regulated during germ
      cell development, suggesting their roles in spermatogenesis.

PMID- 8267599
TI  - Effect of salt concentration on TTF-1 HD binding to specific and non-specific DNA
      sequences.
AB  - The Thyroid Transcription factor 1 (TTF-1) recognizes specific DNA sequences by a
      Homeodomain (TTF-1 HD). The TTF-1 HD DNA-binding properties with both specific
      and non-specific DNA sequences were investigated. TTF-1 HD exists as a monomer in
      solution and as a monomer binds DNA. At 75 mM KCl, its relative binding affinity
      with a specific DNA sequence is about 50 fold higher than with a non-specific DNA
      sequence. Increase of KCl concentration reduces the apparent binding affinity
      both to specific and non-specific DNA sequences. However, non-specific binding is
      more sensitive than specific binding to the increase of salt concentration. When
      DNA-binding reactions are performed at temperature and salt concentration close
      to the intracellular environment, TTF-1 HD binds the specific sequence with an
      affinity at least 1000 fold higher respect to the non-specific sequence.

PMID- 8267600
TI  - Expression of APP in brains of transgenic mice containing the entire human APP
      gene.
AB  - A major component of amyloid deposits found in Alzheimer disease and Down
      syndrome is the beta/A4 peptide, which is derived from the Alzheimer amyloid
      protein precursor (APP). Recent evidence indicates that increases in APP
      expression and/or beta/A4 peptide accumulation may underlie the amyloidosis
      characteristic of these diseases. In the present study, transgenic mice carrying
      the entire human APP gene were studied for expression of human APP. Significant
      expression of human APP protein was observed in these animals, and this
      expression paralleled the expression of endogenous APP. These results, which
      represent a first demonstration of significant human APP expression in transgenic
      animals, support the use of such animals to study human APP expression and
      processing in vivo and possibly as models for the amyloidosis associated with
      Alzheimer disease.

PMID- 8267601
TI  - Biochemical properties of a novel 28KDA protein tyrosine kinase partially
      purified from the particulate fraction of rat spleen.
AB  - In this report we present some of the biochemical properties of the enzyme, here
      called pp28(PTK), isolated from particulate fraction of rat spleen (1). The
      kinase is very susceptible for polyions as regulators of the enzymatic activity.
      The polyanions like dextran sulfate or heparin inhibited, and polycations such as
      spermidin, protamin, poly-L-lysine and some random polypeptides containing
      tyrosine besides a basic amino acid, stimulated the enzyme markedly. The kinase
      showed high sensitivity towards class IA salts. In the casein phosphorylation
      reaction the apparent Km value for ATP was 4 microM. An unusual property is
      associated with autophosphorylation which leads to a reduced activity towards
      external substrates. Some kinase inhibitors described in the literature were
      tested for their potency.

PMID- 8267602
TI  - The marked pH dependence of the talin-actin interaction.
AB  - The effect of pH on the interaction between talin and actin was examined by using
      cosedimentation assays, low shear viscometry, and electron microscopy. When the
      pH at which the interaction was tested was lowered from 7.5 to 7.0 and below, the
      ability of talin to cosediment with F-actin was greatly enhanced, with maximal
      binding at pH 6.6. Talin's ability to increase the low shear viscosity of F-actin
      solutions was also significantly elevated as pH was decreased from 7.4 to 6.6.
      Electron microscope observations of negatively stained actin controls and talin
      actin mixtures supported these results by demonstrating an increase in the degree
      of crosslinking of actin filaments in the presence of talin at pH values of 7 and
      lower.

PMID- 8267603
TI  - Regulation of mucin gene expression in secretory epithelial cells.
AB  - To gain insight into the regulation of mucin biosynthesis and secretion at a
      molecular level, we studied the expression of four mucin genes in several
      secretory cell types. Oligonucleotide probes for MUC1, MUC2, MUC3, and MUC4 were
      used in Northern blot analysis of total RNA from the cells. It was shown that
      MUC4 was constitutively expressed in the endometrial cell line (Ishikawa), which
      we use as a model system for studying airway mucin. Expression was enhanced by
      secretagogues. Cultured bronchial epithelial cells gave identical results. MUC1,
      MUC2, and MUC3 were not detected in either cell system. Secretory phase
      endometrial tissues also expressed only MUC4, but proliferative tissues expressed
      both MUC4 and MUC1. The data indicate that the mucin genes are differentially
      expressed in various cells and suggest a possible regulatory role for steroid
      hormones.

PMID- 8267604
TI  - Angiogenin enhances actin acceleration of plasminogen activation.
AB  - Angiogenin interacts with actin to form a complex, which like actin itself, can
      accelerate plasmin generation by tissue plasminogen activator (tPA). In contrast
      to actin, the angiogenin-actin complex does not inhibit plasmin activity. In the
      presence of the angiogenin-actin complex, the overall proteolytic activity of a
      mixture of plasminogen and tPA is 11-fold higher than in its absence and 6-fold
      higher than in the presence of actin alone. These results suggest that binding
      and displacement of cell surface actin by angiogenin might be involved in cell
      migration and tumor invasion, processes that depend on the proteolytic
      degradation of basement membrane and the extracellular matrix. Therefore, the
      activity of the angiogenin-actin complex reported here may have physiological and
      pathological significance in the process of angiogenin-induced angiogenesis.

PMID- 8267605
TI  - A 24,500 Da protein derived from rat germ cells is associated with sertoli cell
      secretory function.
AB  - A function and identify of a 24,500 Da protein derived from round spermatids of
      the rat testis was investigated with a specific polyclonal antiserum raised
      against RSP-24.5. The proteins released from cultured round spermatids
      significantly stimulated the secretion of de novo synthesized protein from
      cultured immature rat Sertoli cells 2.4-fold above control levels.
      Immunoprecipitation of RSP-24.5 from round spermatid protein further enhanced the
      stimulation of Sertoli cell protein secretion up to 3.1-fold above control
      levels, indicating that RSP-24.5 plays a role in the down regulation of Sertoli
      cell secretion. The antiserum recognized the 24,500 Da protein in Western blots
      of round spermatid protein, pachytene spermatoctye protein, Sertoli cell lysate
      and peritubular myoid cell lysate. A 40 amino acid sequence of a cyanogen bromide
      cleaved internal fragment of RSP-24.5 showed 80.5% homology to a
      phosphatidylethanolamine binding protein. These results suggest that
      phosphatidylethanolamine binding protein participates in the negative regulation
      of Sertoli cell secretory function during spermatogenesis.

PMID- 8267606
TI  - Mechanism-based catalytic antibody inactivation.
AB  - Studies of alternative substrates of the catalytic monoclonal antibodies 18H4,
      7D4, and 45A11 provided us with a better understanding of the mechanism of ester
      hydrolysis employed by these isoabzymes. The antibodies were studied with analogs
      of the substrate, phenyl acetate; N-acetylglycine phenyl ester 3 and N
      carbobenzoxy-glycine phenyl ester 4. All three antibodies catalyzed 3 hydrolysis
      with kinetic constants similar to those seen with phenyl acetate hydrolysis.
      However, 4 was found to be a mechanism-based (suicide) inactivator of 18H4 with a
      kinact of 0.29 min-1 and a K' of 64 microM. Antibody 18H4 was inactivated by 4
      after 3.6 turnovers resulting in the acylation of 1.6 tyrosines per combining
      site. The data conform to a mechanism in which an inactive O-ZGly-tyrosyl
      antibody is formed via a Michaelis complex.

PMID- 8267607
TI  - Transcription factors DNA-binding activity in rat thymocytes undergoing apoptosis
      after heat-shock or dexamethasone treatment.
AB  - The onset of apoptosis is generally thought to require the induction of a novel
      genetic program. Accordingly, we studied the kinetic of DNA-binding activity of
      several transcription factors in rat thymocytes undergoing apoptosis induced by
      dexamethasone (DEX) or heat shock (HS) treatment. Here we report that: 1) early
      activation of AP-1 occurred in both models of apoptosis, even if the intensity of
      activation and AP-1 complex composition were different and much less evident in
      HS-treated thymocytes; 2) early NFkB DNA-binding activity was also observed in
      both types of apoptosis; 3) downregulation of other transcription factors, such
      as OCT-1 and CREB, with high constitutive activity, was recorded in both models
      of apoptosis. The fact that some TFs are up-regulated while others are down
      regulated suggests that apoptosis is the result of a complex combination of
      positive and negative signals regulating gene expression.

PMID- 8267608
TI  - Rapid activation of apoptosis in human promyelocytic leukemic cells by (+/-)-anti
      benzo[a]pyrene diol epoxide induced DNA damage.
AB  - Genotoxic damage in responsive mammalian cells is implicated as a critical event
      in the induction of apoptosis. We have evaluated the time course of activation of
      apoptosis in HL-60 cells following treatment with (+/-)-anti-BPDE metabolite, a
      well established DNA damaging carcinogen. Programmed cell death, determined by
      typical cellular and molecular markers of apoptosis, was apparent with 1.5 h
      following treatment with varying concentrations of (+/-)-anti-BPDE. The fraction
      of apoptotic cell population and corresponding DNA fragmentation indicated a
      minimum threshold damage (approximately 1-2 x 10(-5) adduct/base or about 1
      putative lesion/human gene) necessary to elicit apoptosis. Suppression of
      apoptosis (60-90% inhibition of DNA fragmentation) by 3-aminobenzamide and lack
      of an effect by aphidicolin indicated the role of poly(ADP-ribosylation) but not
      of blocked DNA replication. Our data suggest that DNA damage triggers an acute
      response that sets the responsive cells on path of an "immediate apoptotic" mode
      of cell death.

PMID- 8267609
TI  - Novel potential mechanism-based inhibitors of human leukocyte elastase and
      cathepsin G: derivatives of isothiazolidin-3-one.
AB  - A series of heterocyclic compounds designed to function as mechanism-based
      inhibitors of human leukocyte elastase and cathepsin G has been synthesized and
      their inhibitory activity was investigated. These isothiazolidin-3-one
      derivatives were found to be effective inhibitors of cathepsin G.

PMID- 8267610
TI  - The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent
      anandamide metabolism.
AB  - Anandamide (arachidonylethanolamide) has been identified as a brain constituent
      that selectively binds to the cannabinoid receptor and possesses cannabimimetic
      activity. Cytochromes P450 catalyze the oxidation of arachidonic acid to several
      metabolites possessing very potent pharmacological activity. We examined whether
      P450 would also metabolize anandamide, and whether cannabidiol (a cannabinoid
      which inactivates several P450s) would affect this metabolism. Mouse hepatic
      P450s were found to metabolize anandamide to at least 10 different metabolites,
      four of which were characterized by mass spectrometry. Cannabidiol selectively
      inhibited the formation of two of these four anandamide metabolites. The
      significance of anandamide metabolism remains to be explored.

PMID- 8267611
TI  - Functional polymorphism in the parental imprinting of the human IGF2R gene.
AB  - The murine genes coding for insulin-like growth factor II (Igf2) and its specific
      receptor (Igf2r) are parentally imprinted, with exclusive expression from the
      paternal (Igf2) or maternal (Igf2r) gene copy. We have demonstrated that the
      human IGF2 gene is imprinted, like its murine homologue. To examine whether the
      human IGF2R is also imprinted, we used CA repeat polymorphisms of the cDNA
      sequence to distinguish expression from each copy. Unlike the mouse, most
      subjects equally expressed both gene copies. However, two out of 14 informative
      fetuses showed exclusive expression from the maternal gene copy. We conclude that
      the human IGF2R gene is parentally imprinted, like its murine homologue, but only
      in a minority of individuals. This is the first direct demonstration of
      imprinting as a polymorphic trait, a property that had been observed in transgene
      methylation and predicted from the behavior of certain human tumors.

PMID- 8267612
TI  - FT-IR spectroscopy indicates that Ca(2+)-binding to phosphorylated C-terminal
      fragments of the midsized neurofilament protein subunit results in beta-sheet
      formation and beta-aggregation.
AB  - The Fourier-transform infrared (FT-IR) spectra in trifluoroethanol (TFE) of
      phosphorylated peptides, NF-M17(Ser6P) and NF-M17(Ser11P) representing the C
      terminal repeating domain of the midsized neurofilament protein subunit (NF-M)
      have been measured. In the absence of Ca2+ ions both phosphopeptides adopt
      predominantly aperiodic conformation with minor amounts of beta-turns, 3(10)
      helix or beta-pleated sheet. Addition of Ca(ClO4)2 results in opaque solutions,
      and in the case of the Ser6P peptide, precipitation. The infrared spectra of the
      supernatants reflect the presence of unordered and beta-sheet structure. The
      infrared spectrum of the solid Ca(2+)-complex of NF-M17 (Ser6P) in a KBr pellet
      shows amide component bands at 1654 (alpha-helix or loops) and 1626.5 cm-1 (beta
      sheet). The high intensity of the beta-sheet component suggests extensive beta
      aggregation. The data reported herein give an infrared spectroscopic support to
      our previous findings that upon Ca2+ binding, phosphorylated NF-M fragments
      undergo a marked conformational change which gives rise to partial beta-sheet
      formation and beta-aggregation. This observation may have relevance to the
      molecular events which lead to the accumulation of abnormal proteineous
      structures in Alzheimer's disease.

PMID- 8267613
TI  - Role of isoprenoid metabolism in chemotactic peptide receptor-mediated G protein
      activation.
AB  - The role of isoprenylation in formyl peptide receptor-mediated G protein
      activation was studied using plasma membranes isolated from normal HL-60
      granulocytes and from cells in which isoprenylation was inhibited with
      mevastatin. Plasma membrane expression of formyl peptide receptors and G protein
      beta subunits, but not alpha i2 and alpha i3, was significantly reduced by
      inhibition of isoprenylation. This reduced expression resulted in impaired basal
      and fMet-Leu-Phe-stimulated G protein activation.

PMID- 8267614
TI  - Evidence for predominantly paracellular transport of thyrotropin-releasing
      hormone across CACO-2 cell monolayers.
AB  - Uptake, transport, and metabolism of tripeptide thyrotropin-releasing hormone
      were examined in the human intestinal epithelial cell line, Caco-2. A linear
      relationship between rate and concentration was observed for both the uptake and
      the transport of thyrotropin-releasing hormone across Caco-2 cell monolayers.
      Transport of thyrotropin-releasing hormone was not affected by the presence of
      dipeptide glycylsarcosine, amino acid glycine, tripeptide thyrotropin-releasing
      hormone free acid as well as active transport inhibitors 2,4-dinitrophenol,
      sodium azide, ouabain, and amiloride. There was no formation of metabolites
      during the course of thyrotropin-releasing hormone transport across Caco-2 cells.
      Incubation of Caco-2 cell homogenate with thyrotropin-releasing hormone, however,
      showed a time-dependent hydrolysis of thyrotropin-releasing hormone and the
      formation of thyrotropin-releasing hormone free acid. Increased rate of transport
      in the presence of EDTA indicates a paracellular passive diffusion as the major
      route for the transport of TRH. The hydrolytic enzyme present in Caco-2 cells
      appeared to have little or no access to TRH during the transcellular transport
      across Caco-2 cell monolayers.

PMID- 8267615
TI  - Regio- and stereoselectivity of cytochrome P-450 and peroxygenase-dependent
      formation of cis-12,13-epoxy-9(Z)-octadecenoic acid (vernolic acid) in Euphorbia
      lagascae.
AB  - Two oxygenases associated with microsomes prepared from Euphorbia lagascae
      developing seeds were found to convert linoleic acid into cis-12,13-epoxy-9(Z)
      octadecenoic acid (vernolate): a cytochrome P-450 and a peroxygenase. The
      cytochrome P-450 dependent epoxidation is characterized by a remarkable regio-
      and enantioselectivity, i.e. only the 12(S),13(R)-enantiomer is formed in the
      endosperm. In germinating seeds, peroxygenase was active but no cytochrome P-450
      epoxidase could be detected. Moreover, because of the very high
      enantioselectivity of the fatty acid epoxide hydrolase, which is also found in
      these tissues and which preferentially hydrates the 12(R),13(S)-epoxide
      enantiomer, 12(S),13(R)-epoxy-9(Z)-octadecenoic acid is the only isomer which can
      accumulate in E. lagascae.

PMID- 8267616
TI  - Determination of the human liver UDP-glucuronosyltransferase 2B4 domains involved
      in the binding of UDP-glucuronic acid using photoaffinity labeling of fusion
      proteins.
AB  - The interactions between UDP-glucuronic acid and two human liver UDP
      glucuronosyltransferase 2B4 peptides (14-150 and 299-446) purified from E. coli
      as Staphylococcus aureus protein A fusion proteins have been investigated.
      Photoaffinity labeling with azidonucleotides ([beta-32P]5N3UDP-Glucuronic acid
      and [beta-32P]5N3UDP-Glucose) and competition experiments with UDP-glucuronic
      acid and structurally related compounds emphasized the presence of a specific UDP
      binding site between amino acids 299 and 446. Moreover, competition experiments
      strongly suggested an interaction between the amino terminal part of the protein
      and glucuronic acid. It would involve an electrostatic bond in the binding of the
      cosubstrate via the carboxyl group of UDP-glucuronic acid and a positively
      charged amino acid of the N-terminal domain of the enzyme.

PMID- 8267617
TI  - Flavodoxin is required for the activation of the anaerobic ribonucleotide
      reductase.
AB  - The inactive anaerobic ribonucleotide reductase from Escherichia coli is
      transformed by a multienzyme system and S-adenosylmethionine + NADPH into a
      radical protein that is enzymatically active. One of the activating enzyme
      components was earlier shown to be ferredoxin (flavodoxin):NADP+ reductase. Here
      we present evidence that flavodoxin, but not ferredoxin, also is a component of
      the system. Light reduced deazaflavin can substitute for the flavodoxin system.
      An additional unidentified low-molecular weight component further stimulates the
      reaction.

PMID- 8267618
TI  - Peroxidase-catalyzed desulfonation of 3,5-dimethyl-4-hydroxy and 3,5-dimethyl-4
      aminobenzenesulfonic acids.
AB  - Horseradish peroxidase (HRP), lignin peroxidase (LiP), and Mn(III)-malonate (a
      manganese peroxidase mimic) oxidized 3,5-dimethyl-4-hydroxybenzenesulfonic acid
      (I) to 2,6-dimethyl-1,4-benzoquinone (III) and 2,6-dimethyl-1,3,4
      trihydroxybenzene (IV). Only LiP was efficient at oxidizing 3,5-dimethyl-4
      aminobenzenesulfonic acid (II); LiP oxidized II to 2,6-dimethyl-1,4-benzoquinone
      (III) and 2,6-dimethyl-3-hydroxy-1,4-benzoquinone (V). In these reactions, the
      H2O2-oxidized peroxidases or Mn(III)-malonate oxidized the aromatic ring by two
      electrons to produce a cation. Nucleophilic attack by water on the sulfonic acid
      bearing carbon eliminated sulfonic acid as inorganic sulfite and produced 2,6
      dimethyl-1,4-benzoquinone (III). Possible mechanisms for the formation of IV and
      V are discussed.

PMID- 8267619
TI  - Autophagic degradation of N-linked glycoproteins is downregulated in
      differentiated human colon adenocarcinoma cells.
AB  - The aim of the present study was to elucidate the mechanism responsible for the
      high mannose glycoprotein instability in undifferentiated HT-29 cells (a human
      colon cancer cell line) reported previously. The results presented here are
      consistent with lysosomal degradation of these molecular species. In addition
      inhibitors of the autophagic-lysosomal degradative pathway (3-methyladenine,
      okadaic acid and asparagine) dramatically block the degradation of proteins and N
      linked glycoproteins in undifferentiated HT-29 cells. The main conclusions of
      this work are: 1- the autophagic-lysosomal pathway is responsible for the high
      mannose glycoprotein degradation in undifferentiated HT-29 cells; 2- this
      degradative pathway exists in differentiated cells but is greatly reduced (3.5-4
      fold); 3- the HT-29 cell line is a new model to investigate the molecular
      regulation of autophagy.

PMID- 8267620
TI  - Defective receptors for platelet-derived growth factor AA in human fibroblasts
      with mutant insulin receptors.
AB  - Leprechaunism is an inherited disorder characterized by growth restriction and
      severe insulin resistance and caused by mutations in the insulin receptor gene.
      Cells from these patients have defective insulin binding. Fibroblasts from some
      patients have concomitant defects in other tyrosine kinase receptors, such as
      those for Insulin-like Growth Factor I (IGF-I) and Epidermal Growth Factor (EGF).
      In this report, binding of insulin, IGF-I, EGF, and Platelet derived growth
      factor (PDGF) AA and PDGF-BB is compared among fibroblasts of patients with
      defined mutations in their insulin receptor gene. Fibroblasts from patient Atl-1,
      homozygous for a R86P substitution in the insulin receptor, had reduced binding
      of Platelet-Derived Growth Factor AA (PDGF-AA), a specific ligand for type alpha
      PDGF receptors. The reduction in PDGF binding impaired the ability of this growth
      factor to stimulate DNA synthesis.

PMID- 8267621
TI  - Cationic lipids improve antisense oligonucleotide uptake and prevent degradation
      in cultured cells and in human serum.
AB  - The power of antisense phosphodiester oligonucleotides (aODN) as regulatory
      molecules of gene expression is strongly limited by their low cellular uptake and
      very rapid nuclease-mediated degradation. This study deals with the effect of
      artificial cationic lipids on ODN cellular uptake and degradation in cell
      cultures and in human serum. At the ODN levels normally used in antisense
      mediated gene regulation experiments, a cationic lipid, DOTAP, enhances the rate
      of ODN uptake more than 25 fold, but at lower ODN levels the effect of DOTAP is
      absent. These findings are consistent with a mechanism of ODN internalization by
      receptor-mediated saturable endocytosis that is bypassed by DOTAP. ODN
      degradation by nucleases is markedly prevented by DOTAP both in cultured cells
      and in human serum. Other cationic lipids, namely DOTMA and DOGS, exhibit very
      similar behaviour. The relatively slight cellular toxicity revealed by cationic
      lipids contribute to render these molecules very suitable for aODN vehiculation.

PMID- 8267622
TI  - Cross-sectional analysis of Met235-->Thr variant of angiotensinogen gene in
      severe, familial hypertension.
AB  - A recent cross-sectional study of HTs in Salt Lake City and Paris has reported a
      significant association of a T704-->C (Met235-->Thr) variant in exon 2 of the
      angiotensinogen gene (AGT) with essential hypertension (HT). The present study
      used a new, direct PCR technique to detect this variant in 92 Caucasians with
      severe hypertension (HT) and two HT parents and 94 normotensive (NT) controls.
      Although frequency of the variant in HTs (0.42) was higher than in NTs (0.39),
      the difference was not significant (chi 2 = 0.24; P = 0.63). Plasma
      angiotensinogen showed a weak, nonsignificant relationship with AGT genotype in
      females and no genotypic relationship was apparent for blood pressure. Thus, if
      the Met235-->Thr variant of AGT is involved in essential HT, then its
      contribution may be, at best, much weaker in other HT groups.

PMID- 8267623
TI  - PEC-60, a novel regulatory peptide reduces cyclic AMP formation in rat caudate
      nucleus.
AB  - PEC-60, a sixty-residue novel regulatory peptide with N-terminal glutamic acid
      and C-terminal cysteine is abundant in intestinal tissue. PEC-60-like
      immunoreactivity is found in catecholamine neurons and intracerebroventricular
      injections of PEC-60 reduce dopamine utilization within the caudate nucleus
      indicating a possible role of this peptide in the central nervous system. We have
      investigated the effect of PEC-60 on cAMP formation in membrane preparations from
      rat caudate nucleus. We have found that PEC-60 significantly and dose-dependently
      reduces basal and forskolin stimulated cAMP production. The results demonstrate
      for the first time the interaction of PEC-60 with specific binding sites that
      regulate adenylate cyclase in inhibitory fashion in rat caudate nucleus.

PMID- 8267624
TI  - Haloacetonitriles are low K1 inhibitors of bacterial dichloromethane
      dehalogenases.
AB  - Distinct dichloromethane dehalogenases from Methylobacterium sp. strain DM4 and
      Methylophilus DM11 were inhibited by low concentrations of haloacetonitriles.
      Chloroacetonitrile (ClCH2CN) showed maximal inhibition at a stoichiometry of 1
      mol inhibitor:1 mol holoenzyme for both enzymes. This stoichiometry is suggestive
      of one active site per holoenzyme or extreme negative cooperativity amongst the
      subunits. Radiolabelled ClCH2CN dissociated completely or partially from the two
      dehalogenases, respectively, during chromatography. This suggested ClCH2CN was
      bound non-covalently.

PMID- 8267625
TI  - tert-butyl hydroperoxide induced [Ca2+]i increase in thymus and thymoma cells.
AB  - The effect of tert-butyl hydroperoxide (t-BOOH) on Ca2+ homeostasis in tumor
      thymocytes in comparison to normal thymus cells has been studied. t-BOOH induces
      an early Ca2+ increase which shows different kinetic and extent in normal and
      tumor thymocytes. However, evidence is reported that in both types of cells it is
      just an epiphenomenon not directly related to late injury event. The different
      effects of various compounds (EGTA, dithiothreitol, deferoxamine and glucose) on
      the early Ca2+ increase and the late LDH release induced by t-BOOH suggest the
      occurrence, only in tumor cells, of some undefined deleterious process related to
      Ca2+ movements.

PMID- 8267626
TI  - Enzymatic formation of hepoxilins A3 and B3.
AB  - Available data obtained so far has indicated that hepoxilin formation from 12
      HPETE is catalyzed by hemin and hemoglobin and is not affected through heating of
      these ferri-heme compounds suggestive of nonenzymatic processes. The present
      paper demonstrates for the first time that 12-HPETE is transformed into the
      hepoxilins A3 and B3 by intact cells (skin subcutis layer) and slices of several
      tissues (brain hippocampus and pineal gland) and that this transformation is
      inhibited by tissue boiling, indicating an enzymatic catalysis. The tissues
      employed are pharmacologically responsive to hepoxilins and hence the present
      data offer biochemical support of a potential biological role for the hepoxilins
      in these tissues.

PMID- 8267627
TI  - Components of the protein translocation machinery in the thermophilic
      cyanobacterium Phormidium laminosum.
AB  - Cyanobacteria possess cytoplasmic membranes, which are common to all eubacteria,
      and an additional internal network of thylakoid membranes. We have investigated
      the distribution of the protein translocation machinery between the two membrane
      systems. We have demonstrated that leader peptidase activity exists in both
      membrane systems, suggesting that newly synthesized protein precursors are
      targeted directly rather than sorted after translocation. Southern blot analysis
      suggests that the leader peptidase is likely to be a single enzyme common to both
      membrane systems. We have also shown that cyanobacteria possess a single SecA
      homologue. These results indicate that the protein translocation machinery in the
      two membrane systems is likely to be the same and leaves open the question of
      what mechanism enables the cell to sort proteins between them.

PMID- 8267628
TI  - Induction of cytochrome P450 1A1 and 1A2 by hyperoxia.
AB  - The effect of hyperoxia (O2 > 95%) for 48 hours on the induction of pulmonary and
      hepatic cytochrome P450 has been investigated in adult male rats. Northern blot
      analysis using six "specific" oligonucleotide probes indicated that CYP 1A1 and
      CYP 1A2 mRNAs in liver and CYP 1A1 mRNA in lung were significantly increased by
      hyperoxic exposure, whereas the major constitutive P450 mRNAs, CYP 2C11 in liver
      and CYP 2B1 in lung, were decreased. Since induction of CYP 1A1 has only been
      reported with the use of exogenously administered xenobiotics, further studies
      were carried out to confirm the results obtained with Northern blot analysis.
      cDNAs were synthesized for CYP 1A1 and 1A2 in the liver and CYP 1A1 in the lungs
      and amplified by reverse PCR. These results indicate that these cDNAs were
      amplified significantly more in the hyperoxia group than in the control animals.
      Futhermore, CYP 1A1 and 1A2 proteins in liver and CYP 1A1 protein in lungs as
      well as the corresponding monooxygenase activities were increased by hyperoxia.
      Hyperoxic induction of CYP 1A1 and 1A2 is the first demonstration of nonexogenous
      CYP 1A induction in animals and indicates the needs to pursue the changes of Ah
      receptor-ligand-DNA interaction in hyperoxia.

PMID- 8267629
TI  - Functional analysis of hepatitis B virus transactivator X: implication of the
      leucine zipper-like region and C-terminal seven conserved amino acids in
      functional regions.
AB  - X protein of hepatitis B virus (HBV-X) is a transactivator to a wide variety of
      viral and cellular transcriptional regulatory elements. Since HBV-X does not act
      on a common cis-regulatory element of a wide variety of regulatory elements nor
      does it bind to DNA directly, it has been proposed that HBV-X acts indirectly
      through protein-protein interactions with other transcription factors or signal
      transducing pathway. In order to determine the functional domain of HBV-X, we
      have constructed and analyzed a number of deletion and site specific mutants. Our
      results showed that leucine zipper-like sequences were found in the C-terminal
      region of HBV-X and were very important for its transactivating activity. In the
      analysis of deletion mutants, seven conserved and strong basic amino acids (amino
      acids 135-141) were essential for the transactivating activity of HBV-X.

PMID- 8267630
TI  - Rapid heat production associated with excitation of electric organs of the
      electric eel.
AB  - By constructing a new type of thermal detector, rapid production of heat was
      demonstrated during the rising phase of the action potential of the eel electric
      organs evoked by direct electric stimulation. Following the indirect (synapse
      mediated) action potential of the organs, the existence of very large and
      variable production of heat of unknown origin was revealed.

PMID- 8267631
TI  - Okadaic acid inhibits glucocorticoid-induced apoptosis in T cell hybridomas at
      its late stage.
AB  - Glucocorticoids induce apoptosis in murine T cell hybridomas. It was inhibited by
      okadaic acid and calyculin A, potent inhibitors of protein phosphatase 1 and 2A,
      but not by 1-norokadaone, a structural analog of okadaic acid without phosphatase
      inhibitory activity. The inhibitory effect of okadaic acid was significant even
      when it was added 9 h after the start of the culture. Okadaic acid did not
      prevent either the translocation of glucocorticoid receptor from the cytoplasm to
      the nucleus or the induction of luciferase activity in the T cell hybridoma
      transfected with a plasmid containing the luciferase gene under the control of
      glucocorticoid response elements. These results indicate that protein
      dephosphorylation is an essential step for glucocorticoid-induced apoptosis in T
      cell hybridomas, and that the step is at the late stage of the apoptotic process.

PMID- 8267632
TI  - Chromosomal localization of the epsilon 1, epsilon 3 and zeta 1 subunit genes of
      the human NMDA receptor channel.
AB  - Partial complementary DNAs for the epsilon 1, epsilon 3 and zeta 1 subunits of
      the human N-methyl-D-aspartate (NMDA) receptor channel were cloned using the
      corresponding mouse subunit cDNA clones as probes. Genomic DNA clones for the
      human epsilon 1, epsilon 3 and zeta 1 subunit genes were isolated using the
      corresponding partial cDNA clones as probes. By the fluorescence in situ
      hybridization, we mapped the genes for the epsilon 1, epsilon 3 and zeta 1
      subunits of the human NMDA receptor channel to chromosomes 16p13, 17q25 and 9q34,
      respectively.

PMID- 8267633
TI  - Antifreeze glycoproteins increase solution viscosity.
AB  - A new microsensor that can analyze microliter volume samples was used to measure
      the viscosity of aqueous solutions of antifreeze glycoproteins as a function of
      temperature and concentration. The results show that at physiological
      concentrations which naturally occur in the fish, the antifreeze proteins
      significantly increase aqueous solution viscosity. The probability for ice
      nucleation is inversely proportional to viscosity. Therefore, the increased
      viscosity could explain, in part, reports on the beneficial effects of antifreeze
      glycoproteins during cryopreservation by vitrification. Reducing the probability
      for ice nucleation could be also beneficial for the survival of cold-water fish
      in their natural habitat. Millimolar concentrations of antifreeze proteins
      increase aqueous solution viscosity to values comparable with those of
      conventional cryoprotectants in molar concentrations.

PMID- 8267634
TI  - Developmental regulation of sterol carrier protein 2 in chicken intestine and
      liver at time of hatching.
AB  - Sterol Carrier Protein 2, a protein thought to be involved in various aspects of
      intracellular sterol transport and metabolism, was studied in the small intestine
      and liver of chickens near hatching. In the intestine, a sudden shift in
      molecular mass, from 12 kDa to 64 kDa was noted by Western blotting on the day of
      hatching. Immediately post-hatching, the molecular mass returned to 12 kDa but
      the protein was several fold more abundant than prior to hatching. In the liver,
      several molecular mass forms were present at all ages examined but total shift to
      the 64 kDa form was not seen. Following hatching, however, the 12 kDa form became
      more abundant. Regardless of age of bird or molecular mass, the protein was found
      mainly in peroxisomes.

PMID- 8267635
TI  - Cellular mechanism of glyburide-induced insulin gene expression in isolated rat
      islets.
AB  - The cellular mechanism for the effects of glyburide on the synthesis and release
      of insulin and insulin gene expression in isolated islets was investigated. On
      incubation for 1 h, glyburide increased insulin release without affecting either
      the insulin content or the PPI mRNA level. H-7, an inhibitor of PKC, inhibited
      the glyburide-induced insulin release, while H-8, an inhibitor of cyclic
      nucleotide-dependent protein kinases, did not affect the glyburide-induced
      insulin release. On incubation for 20 h, glyburide increased insulin release and
      the PPI mRNA level, without affecting the insulin content. H-7 inhibited
      glyburide-induced insulin release and increased the PPI mRNA level. H-8
      significantly inhibited both the glyburide-induced increase in insulin release
      and increase in PPI mRNA level. In conclusion, glyburide stimulated insulin
      release via a PKC-mediated pathway and increased the PPI mRNA level via cyclic
      nucleotide-dependent protein kinase(s).

PMID- 8267636
TI  - A novel factor Xa inhibitor: structure-activity relationships and selectivity
      between factor Xa and thrombin.
AB  - A series of 3-amidinoaryl-2-[4-[ [(3S)-3-pyrrolidinyl]oxy]phenyl] propanoic acids
      have been investigated for development of a novel factor Xa inhibitor, possessing
      a potent inhibitory activity for factor Xa and a selectivity for factor Xa
      compared to thrombin. In order to study the structure-activity relationships and
      the selectivity, models of factors Xa complexes formed with the inhibitors were
      constructed on the basis of X-ray crystallographic data of a trypsin-inhibitor
      complex. The models showed that the binding mode of the inhibitors to the S1
      pocket of the enzyme accounted for the structure-activity relationships and that
      the difference between Gln192 of factor Xa and Glu192 of thrombin had a key role
      in the selectivity.

PMID- 8267637
TI  - Activin A induces apoptotic cell death.
AB  - Activins, members of a family of the transforming growth factor beta (TGF beta),
      are involved in the regulation of multiple biological events. We found a novel
      effect of activin A on hybridoma and myeloma cell lines. Activin A exhibited a
      cytotoxic effect on interleukin-6 (IL-6)-dependent B9 cells and induced a
      significant increase in the proportion of fragmented DNA. B9 cells exposed to
      activin A released high amounts of lactate dehydrogenase (LDH) and exhibited the
      typical ladder pattern of DNA fragmentation of apoptotic cells. IL-6 did not
      prevent apoptosis of B9 cells induced by activin A. The cytotoxicity of activin A
      to B9 cells was suppressed by follistatin. On the other hand, TGF beta showed no
      cytotoxic effect on B9 cells. These findings indicate that apoptosis induced by
      activin A could be one of the mechanisms to prevent uncontrolled cell growth.

PMID- 8267638
TI  - Studying block in cloned N-methyl-D-aspartate (NMDA) receptors.
AB  - The biophysics of block of NMDA receptor channels has been investigated
      extensively during the past 8 years. In the last few years, cloned NMDA receptor
      channels have become available. Here we have discussed advantages and
      disadvantages of studying block phenomena in cloned NMDA receptors. Some recent
      work on the pore block of the cloned NMDA receptor channels was critically
      reviewed and extended by data about the calcium block. Novel effects of kainate
      on cloned NMDA receptors and of NMDA on cloned AMPA receptors were reported and
      discussed with respect to recent work concerning possible occurrence of NMDA-AMPA
      hybrid channels.

PMID- 8267639
TI  - Cell death initiated by 3-deazaadenosine in HL-60 cells is apoptosis and is
      partially inhibited by homocysteine.
AB  - Cell death initiated by the adenosine analog 3-deazaadenosine (c3 Ado) was
      studied in human promyelocytic leukemia HL-60 cells. A rapid decrease in cell
      number was seen after 4-hr exposure to 50-100 microM c3 Ado. The dominating mode
      of cell death was apoptosis as demonstrated by condensation and fragmentation of
      the nucleus, formation of apoptotic bodies and endonucleolytic degradation of
      DNA. Four hour treatment with 100 microM c3 Ado resulted in a reduction of early
      S-phase cells, and appearance of cells with a lower DNA and protein content than
      that of the G1 population. Whereas 25 and 50 microM c3 Ado only initiated
      apoptosis in S-phase cells, 75 and 100 microM c3 Ado also initiated apoptosis in
      G1- and G2 + M-phase cells, suggesting different mechanisms for cell death at
      different concentrations. Apoptosis initiated by 100 microM c3 Ado was completely
      inhibited by 1 mM ZnCl2. Addition of homocysteine thiolactone (Hcy) partly
      inhibited cell death by c3 Ado. Light microscopic examination of cultures treated
      with 100 microM c3 Ado and 1 mM Hcy showed nuclear condensation and fragmentation
      consistent with the first stage in apoptosis, however, only a minor formation of
      apoptotic bodies took place in these cultures compared to that observed in
      cultures treated with 100 microM c3 Ado alone. The modifying action of Hcy on c3
      Ado initiated apoptosis in HL-60 cells and this suggests that c3 Ado and 3
      deazaadenosylhomocysteine (c3 AdoHcy) interact with different targets during
      initiation and progression of cell death in this cell line.

PMID- 8267640
TI  - Aphidicolin potentiates apoptosis induced by arabinosyl nucleosides in human
      myeloid leukemia cell lines.
AB  - We investigated the effect of aphidicolin, an inhibitor of DNA polymerase alpha
      and delta, on the induction of apoptosis by arabinosyl nucleosides in a human
      promyelocytic leukemia cell line, HL-60. Pretreatment of HL-60 cells with
      aphidicolin (2 microM) significantly increased the number of morphologically
      apoptotic cells induced by 1-beta-D arabinofuranosylcytosine (ara-C) during 4 hr
      of incubation. This is consistent with the appearance of DNA fragmentation as
      determined quantitatively by diphenylamine or by agarose gel electrophoresis. The
      inhibition of cell growth on day 3 after drug exposure was correlated with the
      degree of apoptosis: Such synergistic interaction between aphidicolin and ara-C
      has also been observed in other human myeloid leukemia cell lines, U937 and KG-1.
      In addition, the induction of apoptosis by 9-beta-D arabinofuranosyladenine or 9
      beta-D arabinofuranosylguanine is augmented by aphidicolin.

PMID- 8267641
TI  - Thiazolidine derivatives as source of free L-cysteine in rat tissue.
AB  - The present study demonstrates that a variety of thiazolidine-4-(R)-carboxylic
      acids (TDs) which are the products of reactions of L-cysteine (cys) with carbonyl
      compounds could serve as a "delivery" system for cys to the cell. Liberation of
      the amino acid can occur enzymatically as well as non-enzymatically. The two
      possibilities have been proven by identification of representative compounds. The
      most specific substrate for mitochondrial enzymatic oxidation was thiazolidine-4
      carboxylic acid (CF), the product of the reaction of cys with formaldehyde, and
      the least metabolized TD was 2-methyl-thiazolidine-4-carboxylic acid (CA), the
      product of the reaction of cys with acetaldehyde. TDs formed from cys and
      different sugars were not metabolized at all in mitochondria. N-Formyl-L-cysteine
      (NFC) the intermediate product of mitochondrial metabolism of CF was ascertained
      by 1H-NMR spectroscopy whereas N-acetyl-L-cysteine (NAC), the predicted
      metabolite of CA, was not detected, possibly due to a fast turnover. The further
      enzymatic hydrolysis of NFC as well as NAC to free cys was demonstrated to take
      place in the cytoplasm. Non-enzymatic hydrolysis of TDs depended on the chemical
      nature of the substituents in the thiazolidine (Th) ring. The most stable
      compound was unsubstituted Th and the least stable were CGlu(D) and CA. Following
      non-enzymatic ring opening and hydrolysis, CA was converted to methyl-djenkolic
      acid, which equilibrates with CA. We have identified this new compound by 1H-NMR
      spectroscopy. TDs may cause both a decrease and an increase in the levels of SH
      groups in mitochondria. In the case of the stable CF, which is metabolized only
      enzymatically, an increase in the levels of SH-groups in mitochondria was
      observed. This suggests that enzymatic control of the breakdown of TDs prevents
      overflowing of the cell with thiol groups. The latter seems to be induced by high
      concentrations of those TDs which are hydrolysed non-enzymatically. This process
      leads finally to a decrease in free SH-groups by different mechanisms. The
      findings demonstrate two different mechanisms by which TDs can provide cys to the
      cells. The biological and pharmacological consequences are discussed.

PMID- 8267642
TI  - Inhibition of epidermal growth factor receptor tyrosine kinase activity by
      hypericin.
AB  - The naphthodianthrone hypericin produces a potent and irreversible inhibition of
      the epidermal growth factor (EGF) receptor tyrosine kinase activity. The
      inhibition was time and temperature dependent but did not depend on EGF
      activation. The IC50 values obtained were 0.37-8.7 microM with membranes
      incubated for 30 min at 30 degrees or 10 min at 0 degree, respectively. Kinetic
      analyses with poly(Glu,Ala,Tyr) 6:3:1 [poly(GAT)] as an exogenous substrate were
      in agreement with the irreversible nature of the inhibition. Irradiation for 30
      min with fluorescent light caused a dramatic photosensitizing effect and resulted
      in an IC50 value of 44 nM. This effect was due to a type I mechanism, since the
      exclusion of oxygen did not alter the inhibition curve. The inhibition was
      inversely proportional to the amounts of membranes used, which probably reflects
      the non-specific sequestration of hypericin into the lipid bilayer. Ser/Thr
      protein kinases such as protein kinase A, casein kinase 1 and 2 and the enzyme 5'
      nucleotidase, were not inhibited by hypericin not even at high concentrations (>
      100 microM).

PMID- 8267643
TI  - Acetone-dependent regulation of cytochromes P4502E1 and P4502B1 in rat nasal
      mucosa.
AB  - The inducibility and molecular regulation of cytochrome P4502E1 (CYP2E1) has been
      examined in nasal mucosa of rats after acetone treatment and compared to that of
      cytochrome P4502B1 (CYP2B1). Twenty-four hours following treatment with acetone
      (5 mL/kg) for 2 days, the amount of CYP2E1 as well as the rate of microsomal 4
      nitrophenol hydroxylase activity had increased by a factor of 2-3, in microsomes
      isolated from nasal mucosa. The increase in CYP2E1 was accompanied by a
      corresponding increase of CYP2E1 mRNA, as determined by northern and slot blot
      analyses. In contrast, hepatic and renal CYP2E1 mRNA, studied in the same rats,
      did not increase, despite the fact that the amount of CYP2E1 was increased 3- and
      5-fold, respectively. The amount of CYP2B1, an isozyme known as acetone-inducible
      in other tissues, decreased significantly by acetone, as detected by immunoblot
      analysis. After 48 hr, the amount of CYP2E1 enzyme, the level of CYP2E1 mRNA and
      the rate of 4-nitrophenol hydroxylase activity had returned to normal levels,
      whereas in liver and kidneys the immunoreactive protein remained 3-4-fold higher
      than control. The results indicate that acetone does not regulate CYP2E1 in nasal
      mucosa by post-translational mechanisms, in contrast to the situation observed in
      liver and kidneys. This indicates a tissue-specific expression of post
      translational regulatory systems responsible for P450 stabilization. Furthermore,
      nasal CYP2B1 also seems to be regulated in a tissue-specific manner by acetone.

PMID- 8267644
TI  - Glucuronidation of diflunisal by rat liver microsomes. Effect of microsomal beta
      glucuronidase activity.
AB  - The in vitro formation rates of the phenolic (DPG) and acyl (DAG) glucuronides of
      diflunisal were investigated using rat liver microsomes. Preliminary studies
      showed that DAG hydrolysed rapidly (T1/2 = 12 min) when incubated in the presence
      of rat liver microsomes at pH 7.4 and 37 degrees. DPG was much more stable under
      the same conditions (T1/2 = 35 hr). Hydrolysis of DAG and DPG by rat liver
      microsomes was inhibited by 4 mM saccharolactone, a beta-glucuronidase inhibitor.
      The apparent Km and Vmax values for the formation of DAG in the absence and
      presence of 4 mM D-saccharic acid-1,4-lactone (saccharolactone) were the
      following: Km = 0.05 +/- 0.02 vs 0.08 +/- 0.02 mM and Vmax = 0.20 +/- 0.06 vs
      0.43 +/- 0.07 nmol/min/mg protein (0 and 4 mM saccharolactone, respectively). The
      significant increase in apparent Vmax for DAG formation in the presence of
      saccharolactone can be explained by the inhibition of beta-glucuronidase
      catalysed hydrolysis of DAG. Apparent Km and Vmax values for the formation rate
      of DPG were not affected by addition of saccharolactone to the incubation medium.
      These results indicate that beta-glucuronidase-catalysed hydrolysis of certain
      glucuronides formed during microsomal incubations may significantly affect the
      apparent glucuronidation rate due to the presence of a glucuronidation
      deglucuronidation cycle.

PMID- 8267645
TI  - Characterization of ecto-ATPase on human blood cells. A physiological role in
      platelet aggregation?
AB  - Ecto-ATPase (EC 3.6.1.15) is a plasma membrane-bound enzyme which degrades
      extracellular triphosphate nucleotides. Although its physiological function is
      still unclear, the enzyme obscures the study of P2 purinoceptors (i.e. receptors
      for ATP and other di- and triphosphate nucleotides), since it is capable of
      metabolizing the pharmacological ligands, such as ATP, for these receptors. We
      characterized the ecto-ATPase activity on human blood cells with a [gamma 32P]ATP
      assay and HPLC measurements. We also determined whether ecto-ATPase activity
      could affect the anti-aggregatory role of ATP in whole human blood. The Km for
      ATP of the ecto-ATPase on human blood cells was 8.5 +/- 2.3 microM and the
      maximum degradation rate, at 37 degrees, was 2.7 +/- 1.1 nmol ATP/(min x mL whole
      blood). In whole blood the major part of ATP was broken down by the blood cells,
      predominantly by the leukocytes. ATP and UTP were broken down equally well,
      mainly yielding the corresponding di- and monophosphates. In search of inhibitors
      for the ecto-ATPase, we studied several analogs of ATP. 8-Bromo-ATP as well as 2'
      and 3'-deoxy-ATP were substrates for the enzyme. In contrast, modification of
      the phosphate side chain yielded inhibitors. Subsequently, a possible role of the
      ecto-ATPase in platelet aggregation was verified. To assess the role of the
      plasma membrane-bound enzyme, platelet aggregation was determined in whole blood
      instead of platelet-rich plasma. In the presence of ATP alone, an antagonist of
      ADP-induced platelet aggregation, some aggregation was still observed. As
      breakdown of ATP by the ecto-ATPase leads to gradual formation of ADP, as
      mentioned above, we compared the effects of a stepwise versus bolus addition of
      ADP. Subsequent dosing of ADP (1.5, 2.5, 5 and 10 microM) resulted in platelet
      aggregation but to a much smaller extent, at most approximately 60%, compared to
      the amount of platelet aggregation obtained with a bolus addition of ADP (10
      microM). In conclusion, human blood cells possess a high affinity ecto-ATPase
      which degrades ATP as well as ATP analogs with modified base and ribose moieties.
      ATP analogs with a modified phosphate chain are inhibitors of the ecto-ATPase. A
      direct role of the ecto-ATPase activity on platelet aggregation is probably
      small, as degradation of ATP to ADP proceeds slowly and cumulative addition of
      ADP to platelets in whole blood results in a modest amount of
      aggregation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8267646
TI  - Cocaine hepatotoxicity: two different toxicity mechanisms for phenobarbital
      induced and non-induced rat hepatocytes.
AB  - Hepatocytes isolated from both phenobarbital-induced and control rats were short
      term cultured and exposed to cocaine (8-2000 microM) for varying times.
      Intracellular lactate dehydrogenase activity, free calcium levels ([Ca2+]i),
      reduced glutathione (GSH) and lipid peroxidation were investigated to evaluate
      the toxic effect of cocaine on hepatocytes. Cytochrome P450 induction by
      phenobarbital potentiated the in vitro cytotoxicity of cocaine by a factor of 13
      (IC50 = 84 microM in induced cells vs 1100 microM in non-induced cells). This
      difference in the susceptibility of the two types of hepatocytes to cocaine
      correlated well with the activity of cytochrome P450 2B1/2. Rapid depletion of
      GSH, reaching 30% of the control levels, and massive lipid peroxidation
      thereafter were the two most remarkable phenomena preceding cell death in
      phenobarbital-induced hepatocytes. On the other hand, a sustained rise in [Ca2+]i
      starting 2 hr after incubation with cocaine was the most noteworthy finding in
      non-induced liver cells. We suggest two different pathways for cocaine
      hepatotoxicity: in phenobarbital-induced hepatocytes oxidative metabolism of the
      drug causes GSH depletion, subsequent extensive lipid peroxidation and cell
      death, at low concentrations of cocaine. In non-induced hepatocytes these changes
      are less relevant, and the major alteration caused by cocaine is a non-transient
      rise in [Ca2+]i that is evident at higher concentrations of the drug.

PMID- 8267647
TI  - Validation of 4-nitrophenol as an in vitro substrate probe for human liver CYP2E1
      using cDNA expression and microsomal kinetic techniques.
AB  - The involvement of human cytochrome P450 (CYP) 2E1 in the hydroxylation of 4
      nitrophenol (4NP) to 4-nitrocatechol (4NC) has been investigated using cDNA
      expression and liver microsomal kinetic and inhibitor techniques. 4NP
      hydroxylation by human liver microsomes and cDNA-expressed human CYP2E1 exhibited
      Michaelis-Menten kinetics; the respective apparent Km values were 30 +/- 7 and 21
      microM. Mutual competitive inhibition was observed for 4NP and chlorzoxazone (CZ)
      (an alternative human CYP2E1 substrate) in liver microsomes, with close
      similarities between the calculated apparent Km and Ki values for each individual
      compound. 4NP and CZ hydroxylase activities in microsomes from 18 liver donors
      varied to a similar extent (3.3- and 3.0-fold, respectively) and 4NP hydroxylase
      activity correlated significantly (rs > or = 0.75, P < 0.005) with both CZ
      hydroxylation and immunoreactive CYP2E1 content. The prototypic CYP2E1 inhibitor,
      diethyldithiocarbamate, was a potent inhibitor of 4NC formation and decreased 4NP
      hydroxylation by cDNA-expressed CYP2E1 and human liver microsomes in parallel.
      Probes for other human CYP isoforms namely (alpha-naphthoflavone, coumarin,
      sulphaphenazole, quinidine, troleandomycin and mephenytoin) caused < 15%
      inhibition of liver microsomal 4NP hydroxylation. These data confirm that, as in
      animal species, 4NP hydroxylation is catalysed largely by CYP2E1 in human liver
      and 4NP may therefore be used as an in vitro substrate probe for the human
      enzyme.

PMID- 8267648
TI  - Regulation of [3H]norepinephrine release by N-methyl-D-aspartate receptors in
      minislices from the dentate gyrus and the CA1-CA3 area of the rat hippocampus.
AB  - It has been reported previously that N-methyl-D-aspartic acid induces a
      significant release of [3H]norepinephrine preaccumulated in slices from the
      hippocampus. In the present study, we investigated whether there are regional
      differences in the hippocampus regarding this N-methyl-D-aspartate effect. In the
      absence of Mg2+, N-methyl-D-aspartate (10-200 microM) induced the release of
      [3H]norepinephrine from superfused minislices containing the dentate gyrus area
      or the CA1-CA3 region of the hippocampus. Such N-methyl-D-aspartate effects on
      [3H]norepinephrine release were significantly higher in the dentate gyrus than in
      the CA1-CA3 area. The N-methyl-D-aspartate effects in both hippocampal areas were
      also reduced significantly by D-2-amino-5-phosphonovaleric acid (50 microM), an
      antagonist of the N-methyl-D-aspartate receptor, and by tetrodotoxin, a blocker
      of the voltage-dependent Na+ channels. The extent of this reduction was the same
      in the dentate gyrus and the CA1-CA3 area. Further experiments, conducted in the
      presence of Mg2+, demonstrated that N-methyl-D-aspartic acid increased K(+)
      induced release of [3H]norepinephrine from dentate gyrus minislices but not from
      the CA1-CA3 area. The results are consistent with the existence of a higher
      density and/or different subtypes of N-methyl-D-aspartate receptors modulating
      [3H]norepinephrine release in the dentate gyrus as compared with the CA1-CA3
      hippocampal area.

PMID- 8267649
TI  - Combination studies with 3'-azido-3'-deoxythymidine (AZT) plus ICI D1694.
      Cytotoxic and biochemical effects.
AB  - The cytotoxicity of 3'-azido-3'-deoxythymidine (AZT), a thymidine analogue, and
      ICI D1694, a folate-based thymidylate synthase (TS) inhibitor, was examined
      individually and in combination in two human tumor cell lines, MGH-U1 bladder
      cancer and HCT-8 colon cancer cells, grown as a monolayer culture with and
      without thymidine (TdR). In addition, TS inhibition, [3H]AZT incorporation into
      DNA, [3H]AZT-MP (monophosphate) production, and DNA double-strand breaks were
      measured. Twenty-four hour exposure of AZT at 0.5, 5, 50 and 500 microM was not
      cytotoxic to MGH-U1 or HCT-8 cells in a colony-forming assay. ICI D1694
      cytotoxicity increased with drug concentration, and the IC50 and IC90,
      respectively, were 0.0064 and 0.01 microM in MGH-U1 cells and 0.009 and 0.018
      microM in HCT-8 cells. TdR in concentrations of 0.1 to 1.0 microM did not affect
      ICI D1694 cytotoxicity in either cell line. AZT at 5, 50 or 500 microM increased
      ICI D1694 cell kill. The IC50 and IC90 for MGH-U1 were 0.0037 and 0.0075 microM
      for 50 microM AZT combined with ICI D1694. The IC50 and IC90 for HCT-8 were
      0.0075 and 0.015 microM for 50 microM AZT plus ICI D1694. The incorporation of
      [3H]AZT into DNA increased with increasing concentrations of ICI D1694.
      Concentrations producing an IC50 and IC90 of ICI D1694, respectively, increased
      incorporation of [3H]AZT into DNA by 319 and 569% in MHG-U1, and 243 and 400% in
      HCT-8 cells. The formation of [3H]AZT-MP paralleled the increase in [3H]AZT
      incorporated into DNA. AZT, ICI D1694 and the combination of AZT and ICI D1694
      caused DNA double-strand breaks, with the combination of these agents being
      additive. CFU-GM survival, exposed to drug concentrations, as those used in the
      tumor cell lines, revealed that the therapeutic index was greater for AZT plus
      ICI D1694 than for ICI D1694 alone. These findings suggest that AZT plus ICI
      D1694 may increase antitumor effect with minimal myelosuppression. We conclude
      that AZT increases the cytotoxicity of ICI D1694 with increasing AZT
      incorporation into DNA.

PMID- 8267650
TI  - Altered gene expression in human leukemia K562 cells selected for resistance to
      etoposide.
AB  - Sublines of K562 human leukemia cells were selected for resistance (30- to 80
      fold) to etoposide by continuous exposure to 0.5 microM VP-16. Two etoposide
      resistant cell lines, K/VP.5 and K/VP.5-1, showed a 5-fold reduction in levels of
      topoisomerase II alpha protein compared with K562 cells. Northern analysis
      indicated a 2.5-fold reduction in topoisomerase II alpha mRNA in etoposide
      resistant cell lines, due in part to a 1.7-fold decrease in topoisomerase II mRNA
      stability with no change in transcription rate. Immunoblotting assays of
      electrophoresed cell lysates from VP-16-treated cells revealed less drug-induced
      covalent topoisomerase II/DNA adducts in resistant than in sensitive cells,
      suggesting a functional alteration in resistant cell topoisomerase II. Recent
      reports of specific topoisomerase II DNA binding sites near the promoter sites of
      growth response genes and alterations of gene expression in cells treated with
      topoisomerase II inhibitory drugs led to experiments to determine if the apparent
      functional alterations of topoisomerase II were accompanied by changes in the
      regulation of these genes. Therefore, the expression of several growth response
      genes was compared by northern analysis in parental K562 and both VP-16-resistant
      cell lines. Basal levels of c-myc were comparable for all three cell lines, but
      levels of c-jun and c-fos were elevated 2- to 4-fold in VP-16-resistant cell
      lines. Increased levels of c-fos and c-jun were not a result of altered rates of
      transcription, as determined by nuclear run-off assays. Exposure of both
      sensitive and resistant cells to 200 microM VP-16 for 5 hr resulted in no further
      changes in topoisomerase II mRNA levels but caused an additional 2- to 3-fold
      elevation in the level of c-jun mRNA, indicating that altered basal levels of
      this gene were not due to deregulation of this gene. Acquired VP-16 resistance in
      K/VP.5 and K/VP.5-1 cells was accompanied by reduced levels and altered
      activities of DNA topoisomerase II as well as changes affecting the expression of
      genes important for growth and differentiation.

PMID- 8267651
TI  - Clofazimine and B669 inhibit the proliferative responses and Na+, K(+)-adenosine
      triphosphatase activity of human lymphocytes by a lysophospholipid-dependent
      mechanism.
AB  - The relationship between the phospholipase-stimulating and immunosuppressive
      properties of the riminophenazine anti-mycobacterial agent clofazimine and its
      experimental analogue, B669, has been investigated in vitro. At concentrations of
      0.6 microM and upwards, both riminophenazines, particularly B669, caused dose
      related inhibition of mitogen- and alloantigen-stimulated uptake of tritiated
      thymidine by human mononuclear leucocytes (MNL), while in short-term assays both
      agents increased the release of lysophosphatidylcholine (LPC) and arachidonic
      acid from these cells. Arachidonate per se at a concentration of 20 microM did
      not affect mitogen-activated lymphocyte proliferation, while cyclooxygenase and
      5'-lipoxygenase inhibitors, as well as water- and lipid-soluble oxidant
      scavengers and anti-oxidant enzymes, failed to protect the cells against the anti
      proliferative effects of clofazimine and B669. However, LPC caused dose-related
      inhibition of lymphocyte proliferation. Moreover, co-incubation of NML with alpha
      tocopherol (vitamin E), a lysophospholipid complex-forming agent, or with
      lysophospholipase, protected the cells against clofazimine and B669, as well as
      against LPC. Na+, K(+)-adenosine triphosphatase was identified as the primary
      target of riminophenazine/LPC-mediated inhibition of lymphocyte proliferation.
      Excessive release of anti-proliferative lysophospholipids during clofazimine or
      B669 treatment of mitogen- or antigen-activated lymphocytes is the probable
      biochemical mechanism of the immunosuppressive activity of these agents.

PMID- 8267652
TI  - Carbon tetrachloride-induced cell death in perfused livers from phenobarbital
      pretreated rats under hypoxic conditions and various ionic milieu. Further
      evidence for calcium-dependent irreversible changes.
AB  - The role of Ca2+ in the initiation of carbon tetrachloride (CCl4) hepatotoxicity
      was studied using perfused livers isolated from phenobarbital-pretreated rats in
      a single-pass system. Krebs-Henseleit bicarbonate buffer containing 1.3 mM CaCl2
      (KHB) was the regular ionic milieu. In the liver perfused with fructose
      supplemented regular KHB equilibrated with 95% N2-5% CO2, infusion of 0.5 mM CCl4
      caused an early uptake of Ca2+ coupled with K+ leakage and Na+ uptake within the
      infusion time of 30 min, which was followed by a marked lactic dehydrogenase
      (LDH) leakage into the effluent perfusate and further Ca2+ uptake by the liver.
      With Ca(2+)-free medium, the prenecrotic K+ leakage and the successive LDH
      leakage were suppressed markedly. However, a perfusate exchange from regular to
      Ca(2+)-free KHB at the end of the prenecrotic stage did not protect against the
      LDH leakage, and the perfusate exchange conversely did not produce LDH leakage.
      Perfusion of the liver with high K+(Cl-) medium under 20% O2 markedly suppressed
      CCl4-induced LDH leakage even in the presence of Ca2+, whereas once CCl4 had
      acted under regular KHB perfusion, changing the medium to high K+ did not further
      prevent the LDH leakage. High K(+)-lactobionic acid medium containing Ca2+ and
      supplemented with fructose also suppressed LDH leakage under 95% N2 without the
      accompanying prenecrotic Ca2+ uptake. However, a change of the medium after CCl4
      infusion to regular KHB containing Ca2+ caused LDH leakage and K+ leakage, with
      Ca2+ uptake. The prevention of LDH leakage in a different ionic milieu may not be
      due to suppression of CCl4 bioactivation, since the liver cytochrome P450 content
      decreased to a similar extent. These findings suggest that entry of extracellular
      Ca2+ into hepatocytes coupled with K+ leakage and Na+ entry is a prerequisite for
      CCl4-induced hepatocyte death and that association of Ca2+ with a CCl4-derived
      radical-mediated process may be necessary for early and irreversible plasma
      membrane damage.

PMID- 8267653
TI  - Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists
      in platelets and aorta.
AB  - Trimetoquinol (TMQ) is a non-prostanoid compound that blocks prostaglandin
      H2/thromboxane A2 (TXA2) receptor-mediated responses initiated by a prostaglandin
      (PG) H2 analog, U46619, in human platelets and rat aorta. Ring fluorine
      substituted TMQ analogs selectively antagonized PG-dependent human platelet
      activation induced by U46619, arachidonic acid, collagen, ADP or epinephrine; and
      were about 300-fold less potent as inhibitors of PG-independent responses
      mediated by thrombin or bacterial phospholipase C. For each inducer of the PG
      dependent pathway, the rank order of inhibitory potency was identical (TMQ > 8
      fluoro-TMQ > 5-fluoro- TMQ). Iodine substitution yielded a similar rank order of
      antagonism against U46619-induced platelet activation (TMQ > 8-iodo-TMQ > 5-iodo
      TMQ), and all TMQ analogs inhibited platelet aggregation in whole blood as well
      as in platelet-rich plasma. Inhibition of specific [3H]SQ 29,548 binding by TMQ
      analogs was highly correlated with inhibition of functional responses to U46619.
      Radioligand binding experiments using TMQ analogs with rat platelets showed no
      interspecies difference in comparison with human platelets. The rank order of
      inhibitory potencies for the fluorinated (but not iodinated) TMQ analogs changed
      in rat thoracic aorta with 8-fluoro-TMQ > TMQ > or = 5-fluoro-TMQ as antagonists
      of U46619-induced vascular contraction. These findings demonstrate that the
      primary mechanism of antiplatelet action of TMQ analogs is related to a blockade
      of TXA2 receptor sites, and ring-halogenated TMQ analogs distinguish between TXA2
      mediated functional responses in vascular smooth muscle and platelets.

PMID- 8267654
TI  - Cholestatic potentials of alpha-naphthylisothiocyanate (ANIT) and beta
      naphthylisothiocyanate (BNIT) in the isolated perfused rat liver.
AB  - Previous studies in rats have shown that a single oral dose of alpha
      naphthylisothiocyanate (ANIT), but not the regioisomer beta
      naphthylisothiocyanate (BNIT), results in intrahepatic cholestasis. The present
      studies were designed to evaluate the intrinsic cholestatic potential of ANIT and
      BNIT in the isolated perfused rat liver. Livers from male Sprague-Dawley rats
      (300-450 g) were isolated and perfused with Krebs-Henseleit buffer supplemented
      with 50 microM taurocholate and ANIT or BNIT (0, 5, 15 or 50 microM). Rates of
      bile flow, bile acid uptake and bile acid excretion were monitored for up to 70
      min. Permeability of tight junctions also was evaluated. At concentrations of 5
      microM, neither ANIT nor BNIT altered hepatobiliary function or tight junction
      permeability. In contrast, perfusion with 50 microM ANIT or BNIT for 35 min
      resulted in decreases in bile flow rates of 19 +/- 8 and 13 +/- 4%, respectively.
      After 70 min of perfusion with ANIT or BNIT, rates of bile flow were decreased by
      78 +/- 5 and 71 +/- 4%, respectively. Bile acid excretion also was decreased
      following perfusion with 50 microM ANIT or BNIT. Perfusion with 50 microM ANIT or
      BNIT decreased bile acid uptake by 51 +/- 13 and 46 +/- 6%, respectively, at 60
      min. Bile/plasma (B/P) ratios of [3H]sucrose were not affected by ANIT or BNIT at
      any time during perfusion, indicating that changes in bile flow and bile acid
      excretion in the isolated perfused liver were not associated with increased
      hepatocyte tight junction permeability. These data demonstrate that the direct
      portal infusion of a 50 microM concentration of either ANIT or BNIT produced
      marked decreases in bile flow, indicating that these isomers have a comparable
      intrinsic cholestatic potential in the isolated perfused liver.

PMID- 8267655
TI  - Dehydrozingerone and isoeugenol as inhibitors of lipid peroxidation and as free
      radical scavengers.
AB  - The antioxidant properties of three related compounds, dehydrozingerone,
      isoeugenol and eugenol, were investigated using various models. Isoeugenol was
      found to be the most active in inhibiting ferrous-ion-, ferric-ion- and cumene
      hydroperoxide-induced lipid peroxidation in rat brain homogenates. These
      compounds also showed significant hydroxyl radical scavenging activity.
      Isoeugenol was potent in scavenging superoxide anion generated by the xanthine
      xanthine oxidase system, whereas eugenol was found to inhibit xanthine oxidase.
      The high antioxidant activity of isoeugenol may be due to the presence of a
      conjugated double bond, which increases the stability of the phenoxyl radical by
      electron delocalization. Such electron delocalization is not possible with
      eugenol. In dehydrozingerone, the stability was decreased by an electron
      withdrawing keto group at the para position.

PMID- 8267656
TI  - Possible role of an iron-oxygen complex in 4(S)-4-hydroxyochratoxin a formation
      by rat liver microsomes.
AB  - Rat liver microsomes were examined for their ability to oxidize the mycotoxin
      ochratoxin A (OTA) to 4(R)-4-hydroxyochratoxin A [(R)-4-OH-OTA] and 4(S)-4
      hydroxyochratoxin A [(S)-4-OH-OTA] and to induce OTA-dependent lipid
      peroxidation. Microsomes isolated from rats pretreated with pregnenolone-16 alpha
      carbonitrile greatly induced both (R)-4-OH-OTA and (S)-4-OH-OTA formation whereas
      isoniazid pretreatment primarily induced (S)-4-OH-OTA. (R)-4-OH-OTA and (S)-4-OH
      OTA formation showed significant differences with respect to pH optima, effect of
      antioxidants, and iron chelators. (R)-4-OH-OTA showed a pH optimum of 6.5 and was
      not inhibited by the antioxidants butylated hydroxyanisole or N,N-diphenyl-1,4
      phenylenediamine or the iron chelators. Desferal or bathophenanthrolinedisulfonic
      acid. In contrast, both (S)-4-OH-OTA and lipid peroxidation showed a pH optimum
      of 7.0 and both activities were sensitive to inhibition by the above antioxidants
      and iron chelators. Lipid peroxidation was not involved in (S)-4-OH-OTA formation
      since addition of linoleic acid hydroperoxide to microsomes did not give rise to
      (S)-4-OH-OTA. Cytochrome P450 appeared to be essential since other hemoproteins
      like horseradish peroxidase and hemoglobin were ineffective in metabolizing OTA
      in the presence of hydroperoxides. The results suggest that (R)-4-OH-OTA is
      formed by normal mixed-function oxidation but that (S)-4-OH-OTA formation may
      involve free iron. It is likely that an active Fe2(+)-oxygen complex, formed via
      NADPH-cytochrome P450 reductase and cytochrome P450-dependent reduction of free
      Fe3+ followed by oxygen binding, serves as the species inducing lipid
      peroxidation and at least part of (S)-4-OH-OTA formation.

PMID- 8267657
TI  - Enhancement of hepatic microsomal esterase activity following soman pretreatment
      in guinea pigs.
AB  - Soman (pinacolyl methylphosphonofluoridate), a highly toxic organophosphate
      compound, has been found to be a strong inhibitor of hepatic microsomal
      carboxylesterase in vitro, but an enhancer of carboxylesterase when administered
      in vivo. In response to this paradoxical observation, the objective of this study
      was to determine if soman could cause true enhancement of the metabolism of drugs
      in the guinea pig and, if so, to characterize the enhanced enzyme activity.
      Following the pretreatment of guinea pigs with 90% LD50 soman, enhancement of
      microsomal esterase activity was noted 12 and 24 hr after pretreatment. Using
      Michaelis-Menten enzyme kinetic studies, enhancement was found to occur with
      liver carboxylesterase and procaine esterase, but not with aniline hydroxylase.
      Since the soman-enzyme complex was known to undergo aging with the release of
      pinacolyl alcohol and the subsequent formation of pinacolone, the effects of
      these metabolites on the activity of liver microsomal enzymes in vitro were
      explored. Pinacolone and pinacolyl alcohol produced enzyme enhancement in vitro
      in a manner similar to that produced by soman pretreatment. These effects were
      compared with those made by acetone in the same incubations, since the enhancing
      influence of acetone has already been well documented. Similarity was found
      between the in vitro effects of acetone and the effects of pinacolone and
      pinacolyl alcohol. Lastly, the in vivo effects of pinacolone on the activities of
      the same liver microsomal enzymes were studied following pretreatment of the
      guinea pigs with 90% LDLo (lowest published lethal dose) pinacolone. Pretreating
      guinea pigs with pinacolone prior to killing them enhanced liver microsomal
      carboxylesterase and procaine esterase activities, but had no effect on
      microsomal aniline hydroxylase activity. This pattern of enzyme enhancement was
      similar to that observed after soman pretreatment. Therefore, soman was found to
      enhance hepatic microsomal esterase activity in the guinea pig in a manner
      similar to that seen with its metabolites, as well as acetone. This information
      may give insight into how the efficacy and toxicity of therapeutic drugs, other
      xenobiotics, and endogenous materials may be altered in individuals who survive
      an exposure to soman.

PMID- 8267658
TI  - Maintenance of viability and transport function after preservation of isolated
      rat hepatocytes in various simplified University of Wisconsin solutions.
AB  - Rat hepatocytes were preserved for 24 hr with high recovery and good maintenance
      of viability and transport function both in University of Wisconsin (UW) solution
      and in various simplified UW solutions. Cell quality is somewhat affected after
      48 hr of preservation in both the original UW solution and the simplified
      solutions. ATP content and uptake rate of taurocholic acid are more sensitive
      markers of cell viability than Trypan blue exclusion or the MTT test. A much less
      expensive solution than UW, containing only K(+)-lactobionate, KH2PO4, MgSO4 and
      raffinose, can be used successfully for preservation of rat hepatocytes for 24 hr
      for drug transport studies.

PMID- 8267659
TI  - Plasma L-arginine levels in a rabbit model of hypercholesterolaemia.
AB  - A novel method for the quantitation of L-arginine in plasma samples has been
      developed, based on the technique of enantiomer labelling coupled to the
      capillary gas chromatographic separation of amino acids. Using this technique
      plasma L-arginine levels have been measured in rabbits fed a 1% cholesterol
      containing diet and compared with rabbits fed a standard diet. Blood cholesterol
      levels were significantly elevated in the rabbits fed cholesterol but no
      significant difference was found in plasma L-arginine levels between the
      cholesterol-fed and control animals. No D-arginine was found in any of the plasma
      samples. It is concluded that the impairment in endothelium-dependent relaxation
      previously described in this animal model of hypercholesterolaemia is not due to
      deficiency of plasma L-arginine.

PMID- 8267660
TI  - Biotransformation of 17 beta-hydroxy-11 beta-(4-dimethylaminophenyl)17 alpha-1
      propynyl-estra-4,9-dien-3-one (RU486) in rat hepatoma variants.
AB  - Metabolism of the synthetic steroid 17 beta-hydroxy-11 beta-(4
      dimethylaminophenyl)17 alpha-1-propynyl-estra-4,9-dien-3-one (RU486) occurs in
      the dedifferentiated S-H56-125 variant of Reuber hepatoma. Considering that rat
      liver cytochrome P450 (P450) monooxygenases are engaged in different oxidative
      steps of the metabolism of RU486, the influence of several prototype P450
      inducers was investigated. The data obtained by treating H56 and S-H56-125
      hepatoma cells with different P450 inducers (dexamethasone (DEX), benzanthracene,
      phenobarbital) or with a specific P450 inhibitor, troleandomycin, led us to
      conclude that CYP3A is involved in the hydroxylation of RU486. This form is
      induced by DEX independently of the availability of the canonical glucocorticoid
      receptor.

PMID- 8267661
TI  - Alleviation of experimental cyclosporin A nephrotoxicity by low dose aspirin in
      the rat.
AB  - Groups of male Sprague-Dawley rats received either cyclosporin A (CsA; 25 mg/kg
      by gavage), low dose aspirin (ASP; 20 mg/kg by gavage), a combination of both, or
      the appropriate drug vehicles daily for 14 days. Renal structure and function
      were assessed on day 0 (pretreatment) and on days 7 and 14. Compared to
      pretreatment results, CsA nephrotoxicity was characterized by increased plasma
      urea and creatinine concentrations and by moderate to severe microcalcification
      (MC) at the corticomedullary junction by day 14. The development of
      nephrotoxicity was also associated with a 5-fold increase in urine thromboxane B2
      (TxB2) excretion by day 10, while that of 6-ketoprostaglandin F1 alpha remained
      relatively constant. Although both ASP and saline (ASP vehicle) -cotreated
      animals demonstrated significantly lower plasma urea and creatinine
      concentrations compared to treatment with CsA alone, the severity of MC observed
      on day 14, was reduced only in the ASP cotreatment group. Though whole blood CsA
      concentrations were similar at around 2400 ng/mL in all experimental groups. In
      addition, although a 2-fold increase in urine TxB2 excretion was observed on days
      7 and 10 following treatment with CsA/ASP, levels were significantly reduced
      compared to treatment with either CsA alone or CsA/saline (both P < 0.05).

PMID- 8267662
TI  - Phenylpyruvic acid may be a direct precursor of mandelic acid without
      intermediate transamination of phenylalanine.
AB  - A series of compounds related to phenylalanine was administered to rats. Output
      of mandelic acid, a major but unexplained metabolite in phenylketonuria, was
      increased after the administration of phenylethanolamine or phenylpyruvic acid,
      whereas phenylethylamine or phenylalanine increased its excretion only
      marginally. Phenylacetic acid, previously suggested as a possible precursor in
      man, was almost without effect. It seems likely that mandelic acid can be formed
      from phenylpyruvic acid directly, without intermediate transamination to
      phenylalanine.

PMID- 8267663
TI  - Degradation products of streptozotocin do not induce hyperglycemia in rats.
AB  - The present study was conducted to determine whether degradation products of
      streptozotocin formed under various conditions induce hyperglycemia in rats.
      Streptozotocin is completely degraded in pH 7.4 buffer in 4 hr and even more
      rapidly in plasma. Streptozotocin degradation products resulting from incubation
      in pH 7.4 phosphate buffer or in plasma were not diabetogenic in rats.

PMID- 8267664
TI  - Analysis of the biological and molecular properties of phencyclidine-like
      compounds by chemometrics.
AB  - The quantitative structure-activity relationships (QSAR's) of 3 series of
      arylcyclohexylamines have been investigated using computational chemistry and
      multivariate statistics. Principal component analysis of the aromatic ring data
      set demonstrated some clustering of activity categories. Biological activity of
      the cyclohexane ring data set was correlated with molar refractivity. These
      findings may be useful for predicting the activity of novel neuroprotective
      agents.

PMID- 8267665
TI  - Studies on the synthesis and antidepressant activity of some 1-thiocarbamoyl-3,5
      diphenyl-2-pyrazolines.
AB  - Several 1-thiocarbamoyl-3,5-diphenyl-2-pyrazoline derivatives have been
      synthesized by reacting 1,3-diphenyl-2-propen-1-one (chalcones) with
      thiosemicarbazide, or hydrazine hydrate and then with various isothiocyanates.
      Their chemical structures have been proven by UV, IR, 1H-NMR and elemental
      analysis. Antidepressant activities were investigated by "Porsolt's Behavioural
      Despair Test". 1-Thiocarbamoyl-3-(phenyl and 4-chlorophenyl-5-(4-methyl and 4
      methoxyphenyl-2-pyrazoline (compounds III, IV, VII, VIII) and 3-(4-methylphenyl)
      5-(4-methoxyphenyl)-2-pyrazoline (compound XII) showed equivalent or higher
      activity than pargyline hydrochloride and tranylcypromine sulfate.

PMID- 8267666
TI  - Antipyrine congeners as antidepressant agents.
AB  - 1-(N-Antipyrinylglycyl)-3-arylideneamino)-2-thiobarbituric acids (III) were
      synthesized from 1-arylidene-4-(N-antipyrinyl glycyl)-3-thiosemicarbazones (II).
      Compounds II in turn were prepared from 4-amino antipyrine. Compounds III were
      finally converted into 1-(N-antipyrinylglycyl)-3-[(3'-chloro-4-aryl)azitidinyl]-2
      t hiobarbituric acids (IV). 4-Aminoantipyrine was also treated with different N
      protected amino acids in the presence of N,N'-dicyclohexylcarbodiimide to yield N
      (antipyrinylcarbamoyl) substituted alkyl benzamides (V); their debenzoylation
      yielded 2-(amino-N-antipyrinyl) substituted acetamides (VI). The compounds were
      screened for their antidepressant activity. Compounds IIId, Va and Vb exhibited
      activity better than imipramine with less toxicity (ALD50 > 1000 mg/kg).

PMID- 8267667
TI  - Effect of 20(S)-ginsenoside-Rg2 and cyproheptadine on two-way active avoidance
      learning and memory in rats.
AB  - The effects of 20(S)-ginsenoside-Rg2 (GRg2, CAS 52286-74-5) and cyproheptadine
      (CYP, CAS 129-03-3) on acquisition, retention and retrieval were examined in male
      Wistar rats using a two-way active avoidance method. Learning and memory were
      estimated by the avoidance rate (%) and/or latency (s). Acute administration of
      CYP 1.0 mg/kg i.p. 30 min prior to training produced a significant impairment in
      acquisition of 3 d learning and 48 h memory by decreasing the rate from 87.9 +/-
      2.1, 75.8 +/- 4.9 in saline rats to 55.8 +/- 9.6, 53.4 +/- 8.4, respectively
      (F(1,14) = 10.7, 14.8, p < 0.01). The CYP administration immediately following
      the end of training and 30 min before testing produced the impairments in
      retention of 24 h memory and in retrieval of 48 h memory by decreasing the rate
      from 86.7 +/- 1.7, 93.3 +/- 2.7 to 55.0 +/- 5.5, 60.0 +/- 6.8, respectively
      (F(1,12) = 27.2, 10.5, p < 0.01). Repeated administration of GRg2 20 mg/kg i.p.
      significantly improved the CYP-induced recognitional deficits by increasing the
      CYP-decreased rate from 55.8 +/- 9.6 to 80.8 +/- 4.2 in d 3 learning acquisition
      (F(1,14) = 5.6, p < 0.05), from 53.4 +/- 8.4 to 60.0 +/- 8.2 in 48 h memory
      acquisition (F(1,14) = 7.5, p < 0.05) and from 55.0 +/- 5.5 to 88.3 +/- 2.5 in 24
      h memory retention (F(1,12) 27.5, p < 0.01) as well as from 60.0 +/- 6.8 to 85.6
      +/- 6.9 in 48 h memory retrieval (F(1,12) = 5.2, p < 0.05), respectively. The
      results also provide the suggestive evidence that central serotonin may play a
      positive modulatory role in the acquisition, retention and retrieval of two-way
      active avoidance responding in rats.

PMID- 8267668
TI  - Synthesis of some 1,4,5,6,7,8-hexahydroquinoline derivatives and their calcium
      antagonistic activity.
AB  - Twenty-seven new 2-methyl-3-acetyl-4-aryl-5-oxo-1,4,5,6,7,8-hexahydroquinoline
      derivatives have been prepared. Their structures were confirmed by UV, IR, 1H-NMR
      and elementary analysis. The calcium antagonistic activity of these compounds was
      tested in K(+)-depolarized taenia coli precontracted with 1 mmol/l Ca+2.

PMID- 8267669
TI  - Comparison between the efficacy and tolerability of oxerutins and troxerutin in
      the treatment of patients with chronic venous insufficiency.
AB  - Oxerutins (Venoruton) and troxerutin (CAS 7085-55-4) are both mixtures of O-(beta
      hydroxyethyl)-rutosides used for the treatment of chronic venous insufficiency.
      As di-O-(beta-hydroxyethyl)-rutosides and 7-mono-O-(beta-hydroxyethyl)-rutoside
      were found to be more active with regard to free radical scavenging compared to
      tri-O-(beta-hydroxyethyl)-rutoside the aim of this study was to compare oxerutins
      and troxerutin clinically. 12 female, post-menopausal patients with chronic
      venous insufficiency grade II participated in this double-blind study with random
      allocation to the treatment groups. They received 900 mg/day oxerutins or
      troxerutin for 12 weeks and were observed for 4 further weeks without treatment.
      Leg volumes (water displacement) and subjective symptoms (VAS, visual analogue
      scale) were evaluated before and following 2, 4, 8, 12 and 16 weeks. Both
      treatments were active in reducing leg volumes and in ameliorating subjective
      symptoms (mean volume reduction -167 +/- 157 ml x week). Volume reduction
      totalled to -261 +/- 154.2 ml x week for oxerutins and -73.2 +/- 97.1 ml x week
      for troxerutin. The difference is statistically significant (p = 0.04). The
      findings with subjective symptoms were in good accordance to the objective volume
      measurement. Oxerutins revealed a remarkable carry over effect.

PMID- 8267670
TI  - Influence of 3,5-dimethyl-3'-isopropyl-L-thyronine on thyroid state and
      gestational outcome in the Wistar rat.
AB  - 3,5-Dimethyl-3'-isopropyl-L-thyronine (DIMIT, CAS 26384-44-1), a non-halogenated,
      artificial analogue of the thyroid hormone T3, was administered once daily by
      intragastric gavage to pregnant Wistar rats on days 17-20 of gestation to
      elucidate the effects of DIMIT on maternal and foetal thyroid state and
      gestational outcome under the influence of low iodine or iodine excess nutrition.
      Doses of 20 micrograms.kg-1.d-1 and 150 micrograms.kg-1.d-1 DIMIT were applied.
      Throughout pregnancy the animals were kept on low iodine diet and either on
      iodine free drinking water or iodine excess. There was no statistically
      significant effect on maternal body weight, weight of living foetus, the rate of
      intra-uterine death before day 16 of gestation, water and food consumption, and
      no hint of maternal thyrotoxicosis. The vital off-spring did not reveal any signs
      of gross malformation. DIMIT decreased serum TSH both in dams and foetus, and
      diminished the TSH stock of the pituitary gland of the dams. T3-levels were also
      lowered in maternal serum by DIMIT. These DIMIT induced effects were observed
      irrespective of iodine deficiency or excess. There was no difference in foetal
      mortality before onset of DIMIT-treatment, but the gestational death rate
      increased in a dose-related manner by the administration of DIMIT. This serious
      adverse effect became apparent at a DIMIT-dose that is not sufficient for a
      complete compensation of foetal hypothyroidism in utero. The higher prenatal
      mortality was accompanied by a decreased placental weight, but not by a reduced
      body weight of surviving foetus.

PMID- 8267671
TI  - Subchronic and chronic toxicity of the new sulfonylurea glimepiride in dogs.
AB  - The new sulfonylurea glimepiride (Hoe 490, CAS 93479-97-1) was tested in
      subchronic and chronic toxicity studies in dogs. Up to and including a dose of 16
      mg/kg b.w. neither toxic effects nor pathological changes were observed in the
      treated animals. Also at a dose of 320 mg/kg b.w. which was applied over a period
      of 6 months no undesired effects were detected. However, after a treatment period
      of 1 year in some of the animals which received 320 mg/kg b.w. cataract formation
      appeared. The mechanism for that still remains unclear but is not due to changes
      in special biochemical reactions as it can be observed with other typical
      cataractogenic chemicals. The relevance of these findings for the application of
      that drug in humans therefore has to be discussed bearing in mind the extremely
      high dose and serum levels as well as the number of animals (2/12) where the
      effects were seen. As expected in all experiments pharmacodynamic effects like
      reduced serum glucose levels and a degranulation of the beta-cells of the
      pancreas were seen. Both effects were completely reversible within the recovery
      period.

PMID- 8267672
TI  - Simultaneous determination of allopurinol and oxipurinol in human plasma and
      urine by high-performance liquid chromatography.
AB  - The uricostatic drug allopurinol (CAS 315-30-0) is used for treatment of
      hyperuricaemia and is mainly bio-transformed to the active metabolite oxipurinol
      (CAS 2465-59-0) in humans. A new assay was developed for the simultaneous
      determination of both compounds in plasma and urine using ultrafiltration and ion
      exchange purification steps for plasma and urine, respectively. Reversed-phase
      high-performance liquid chromatography with ultraviolet detection was applied for
      the separation and quantitation of both compounds. The limit of detection was 0.1
      microgram/ml for both compounds in plasma and 0.2 and 0.5 microgram/ml for
      allopurinol and oxipurinol, respectively, in urine. Within-run and day-to-day
      precision of 3-5% and 5-7% was determined for plasma and 6-8% and 8-10% for urine
      analysis. The assays were further validated using liquid chromatography with
      photodiode array detection and by comparison with methods using protein
      precipitation as the purifying step. The high analytical recoveries, selectivity,
      sensitivity, accuracy and reproducibility were adequate for the measurement of
      both compounds in pharmacokinetic studies and for drug monitoring in patients on
      allopurinol therapy.

PMID- 8267673
TI  - Effects of nocloprost on some monooxygenases of rat and human liver.
AB  - Interactions of the cytoprotective agent nocloprost (9 beta-chloro-16,16-dimethyl
      prostaglandin E2, CAS 79360-43-3) with the microsomal monooxygenase system were
      studied in rat and human liver. Nocloprost did neither bind to human and rat
      liver cytochrome P-450 nor changed the activities of aniline hydroxylase,
      aminopyrine demethylase, ethylmorphine N-demethylase, 7-ethoxycoumarin and 7
      ethoxyresorufin O-deethylase as well as 7-pentylresorufin O-depentylase after in
      vitro incubation with 1 ng/ml. Premedication of rats with 0.1 and 1.0 mg/kg
      lacked significant interferences with the monooxygenases studied.

PMID- 8267674
TI  - Pharmacological effects of the new gastroprokinetic agent mosapride citrate and
      its metabolites in experimental animals.
AB  - The pharmacological effects of the metabolites M1 and M2 of mosapride citrate
      ((+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholi nyl]
      methyl]benzamide citrate, AS-4370, CAS 112885-42-4), a gastroprokinetic agent
      with serotonin 5-HT4 receptor agonist property, were compared with those of
      mosapride. In isolated guinea-pig ileum treated with phenoxybenzamine, the
      metabolites M1 and M2 enhanced electrically-evoked contractions with EC50 values
      of 1.2 x 10(-7) mol/l and 1.0 x 10(-6) mol/l, respectively. The metabolite M1 was
      twice less potent than that of mosapride. When administered intravenously, the
      metabolite M1 enhanced gastric emptying of a semisolid meal in mice and rats; the
      potency was 3 times less than that of mosapride in mice and almost equal to that
      of mosapride in rats. When administered orally, the metabolite M1 enhanced
      gastric emptying of a semisolid meal in mice and rats, and also enhanced gastric
      emptying of a resin pellet meal in rats. The potency of metabolite M1 was 10
      times less than that of mosapride in rats, although it was equal to that of
      mosapride in mice. In these experiments, the metabolite M2 was far less active.
      In addition to these gastroprokinetic properties, the metabolite M1 possessed a
      potent 5-HT3 receptor antagonist property. The metabolite M1 antagonized the 2
      methyl-5-HT-induced bradycardia in anesthetized rats with an ED50 value of 10.5
      micrograms/kg, i.v., and inhibited the cisplatin-induced emesis in ferrets with a
      potency approximately 25 times that of mosapride. These results suggest that the
      metabolites M1 and M2 of mosapride do not play a crucial role in the
      gastroprokinetic effect of mosapride.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267676
TI  - Metabolism of [carbonyl-14C]mosapride citrate after a single oral administration
      in rats, dogs and monkeys.
AB  - The metabolism of mosapride citrate ((+-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4
      fluorobenzyl)-2-morpho li nyl] methyl]benzamide citrate, AS-4370, CAS 112885-42
      4) was investigated in rats, dogs and monkeys after a single oral administration.
      Four metabolites, M-1 to M-4, were isolated from rat urine. Two of them were
      identified as des-p-fluorobenzyl (M-1) and 5'-oxo-des-p-fluorobenzyl mosapride (M
      2) and the other two were considered to be as 3-hydroxy des-p-fluorobenzyl (M-3)
      and 3-hydroxy 5'-oxo-des-p-fluorobenzyl mosapride (M-4) by mass spectrometry
      and/or nuclear magnetic resonance spectrometry. Metabolites in biological
      specimens such as plasma and urine after oral administration of [14C]mosapride in
      rats, dogs and monkeys were analyzed by thin layer chromatography (TLC).
      Unchanged mosapride, M-1, M-2 and some other metabolites were observed in the
      plasma of male rats. On the other hand, female rat plasma contained mosapride as
      the major radioactive component with a small amount of M-1 and little other
      metabolite(s). In rat urine, irrespective of sex, M-1, M-2, M-3, M-4 and a few
      other metabolites were observed but the unchanged drug was hardly detected. These
      facts suggested that the metabolic rate of mosapride was different between sexes
      in rats. In male rat bile, mosapride, M-1 and polar metabolite(s) were observed.
      In dogs, mosapride and M-1 were observed as major radioactive components in
      plasma, and M-1 was seen also as the major metabolite in urine but unchanged drug
      was hardly detected. Similar results were obtained in monkeys.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8267675
TI  - Absorption, distribution and excretion of [carbonyl-14C]mosapride citrate after a
      single oral administration in rats, dogs and monkeys.
AB  - Absorption, distribution and excretion of mosapride citrate ((+/-)-4-amino-5
      chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morph oli nyl] methyl]benzamide citrate,
      AS-4370, CAS 112885-42-4), a novel gastric prokinetic drug, were studied with 14C
      labeled drug in male and female rats mainly after a single oral administration.
      Plasma concentrations and excretion following oral administration of
      [14C]mosapride were also investigated in dogs and monkeys of both sexes. The main
      experimental dose was 10 mg/kg. After oral administration, [14C]mosapride
      radioactivity was rapidly absorbed through the intestinal tract. In male rats,
      concentration of plasma radioactivity reached the maximum (Cmax; 1410 ng eq./ml)
      1 h after administration and decreased biphasically with half-lives of about 2 h
      in alpha-phase (t1/2 alpha) and in beta-phase (t1/2 beta) of about 8 h. t1/2 beta
      was virtually constant in the dose range from 1 mg/kg to 100 mg/kg, and the area
      under the plasma concentration-time curve (AUC) was proportional to the dose. In
      female rats, biphasic plasma concentration-time profile with similar half-lives
      was also observed, but Cmax (2070 ng eq./ml) and AUC were larger than those in
      male rats, suggesting the sex difference in pharmacokinetics. In dogs and
      monkeys, Cmaxs of plasma concentration were about 1000 ng eq./ml and 2000-3000 ng
      eq./ml, respectively, and sex difference was not observed. Plasma concentrations
      declined in a biphasic manner and t1/2 alpha and t1/2 beta were about 4 h and 15
      h in dogs and about 3 h and 10 h in monkeys, respectively. The [14C]mosapride
      radioactivity was distributed to many tissues including the stomach and small
      intestine at the higher concentration, while to the brain and eye ball at the
      lower concentration than the plasma in male rats. Radioactivities in most tissues
      decreased essentially in parallel with those in plasma. In pregnant rats,
      concentrations of radioactivity in fetus were a little higher than those in the
      maternal plasma. In lactating rats, milk radioactivity concentrations were about
      5 times higher than corresponding plasma concentrations, and both of them
      decreased with similar half-lives. Mosapride was bound to serum protein of
      various animal species, albumin and alpha 1-acid glycoprotein, in about 93-99%.
      After oral administration in rats, about 40% of dosed radioactivity was excreted
      into urine and about 60% into feces via bile. Neither dose dependency nor sex
      differences was observed in excretion. In dogs, about 20% of dosed radioactivity
      was recovered in urine and about 70% in feces.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8267677
TI  - Absorption, distribution, metabolism and excretion of [carbonyl-14C]mosapride
      citrate after repeated oral administration in rats.
AB  - Absorption, distribution, metabolism and excretion of mosapride citrate ((+/-)-4
      amino-5-chloro-2-ethoxy-N [[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide
      citrate, AS-4370, CAS 112885-42-4), a novel gastrokinetic agent, were studied
      with 14C-labeled compound in male rats during and after 21 consecutive daily oral
      administration at a dose of 10 mg/kg/d. After the first administration, plasma
      radioactivity concentrations were essentially equal to those in the single dose
      experiment, including the maximum concentration (Cmax; 1130 ng eq./ml) at 1 h.
      Plasma concentrations at 1 h after each administration were virtually constant in
      the range of 770-1350 ng eq./ml for 21 days. On the other hand, the plasma
      concentration at 24 h gradually increased for 6-7 days to about 120 ng eq./ml and
      became substantially constant, suggesting that apparent steady state was achieved
      by around 7 consecutive daily administration. Plasma concentration reached Cmax
      of 1230 ng eq./ml at 0.5 h after the 21st administration and decreased
      biphasically with half-lives of 3.4 h (t1/2 alpha) and 14.9 h (t1/2 beta). t1/2
      alpha was virtually similar but t1/2 beta was about 2 times longer compared with
      single dose experiment. About 40% and 55% of dose radioactivity were excreted in
      urine and feces, respectively, for 21 days and radioactivity was almost
      completely excreted within 168 h after the last administration. The analysis by
      thin layer chromatography elucidated that composition of radioactive metabolites
      in plasma and urine after repeated administration was similar to that in the
      single dose study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267678
TI  - Pharmacokinetics of glucosamine in man.
AB  - The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in
      6 healthy male volunteers (2 per administration route) using 14C uniformly
      labelled glucosamine sulfate and administering it in single dose by intravenous
      (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v.
      administration the radioactivity due to glucosamine appears in plasma and is
      rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration
      the radioactivity due to glucosamine disappears almost completely and is replaced
      by a radioactivity originating from plasma proteins, in which glucosamine or its
      metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and
      then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is
      recovered in the urine of the 120 h following the administration and less than 1%
      is recovered in the feces. After i.m. administration similar pharmacokinetic
      patterns are observed. After oral administration a proportion close to 90% of
      glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma.
      The radioactivity incorporated in the plasma proteins follows pharmacokinetic
      patterns which are similar to those after i.v. or i.m. administration, but its
      concentration in plasma is about 5 times smaller than that after parenteral
      administration. The AUC after oral administration is 26% of that after i.v., or
      i.m. administration. The smaller plasma levels of radioactivity after oral
      administration are probably due to a first pass effect in the liver which
      metabolizes a notable proportion of glucosamine into smaller molecules and
      ultimately to CO2, water and urea.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267679
TI  - Pharmacokinetics of bromfenac in healthy subjects after single oral
      administration of three different doses.
AB  - The pharmacokinetic profile of bromfenac (2-amino-3-(4-bromobenzoyl)
      benzeneacetic acid, CAS91714-93-1) has been investigated in 12 healthy subjects
      (6 male and 6 female) after single oral doses of 25, 50 and 75 mg. Plasma
      concentrations were determined by a sensitive HPLC method with spectrophotometric
      detection. Sampling was performed up to 300 min after drug ingestion. Linear
      pharmacokinetics could be verified for this dose-range; there was a clear,
      positive dose-plasma concentration relationship. Bromfenac exhibits a cmax of
      3.49 +/- 1.65-8.81 +/- 3.45 micrograms/ml at tmax 52 +/- 27-42 +/- 15 min. The
      elimination half-life was 39.8 +/- 7.3-34.2 +/- 8.0 min with a clearance (Cl/f)
      of 120.6 +/- 51.6-135.3 +/- 34.6 ml/min and a volume of distribution (Vd/f) 6.82
      +/- 2.88-6.64 +/- 2.29 l. The results obtained show a fast absorption and rapid
      elimination of bromfenac when administered orally. The short plasma half-life of
      bromfenac apparently presents no direct relationship to its clinical
      effectiveness.

PMID- 8267680
TI  - Increase of alkaline phosphatase in multidrug-resistant tumor cells and their
      cross-resistance to 6-thioguanine.
AB  - The expression of alkaline phosphatase (AP) was analyzed in multidrug-resistant
      (MDR) tumor cells (sarcoma 180, lung carcinoma, and renal cell carcinoma cell
      lines) by means of immunocytochemistry. MDR cell cultures showed an
      overexpression of AP and a cross-resistance to 6-thioguanine (6-TG, CAS 154-42
      7). Significant correlations between AP expression and doxorubicin or vincristine
      resistance and P-glycoprotein (P-170) expression were found in these cell
      cultures. A specific AP inhibitor, levamisole, reversed resistance to 6-TG, but
      not to doxorubicin. This indicates that 6-TG resistance is certainly associated
      to P-170 but a causal function of AP for the development of MDR does not exist.

PMID- 8267681
TI  - Use of a rule based graph-theoretical system in evaluating the activity of a
      class of nucleoside analogues against human immunodeficiency virus.
AB  - A rule based graph-theoretical system has been used to evaluate qualitatively the
      activity of a class of nucleoside analogues against human immunodeficiency virus
      (HIV). The system identifies biologically relevant vertices (atoms) in the
      molecular graphs of the compounds which have the biological activity of interest.
      The idea is to relate biological activity with the structural or substructural
      characteristics of the compounds from the point of view of molecular topology
      (connectivity). The system brings vertices of similar or close topological
      environment in the respective compounds together and this is reflected in the
      ranges of values formed by a distance based index of the vertices, the 'distance
      exponent index (Dx)', where x is any real number. It is found that the system
      makes correct prediction of the activity of all the compounds (active as well as
      inactives) of both training set and the test set against HIV. It is also apparent
      from this study that the index D-4, which has been used here, can make a useful
      classification of the vertices according to their molecular environment and the
      system can produce significant result in a small as well as diverse data base.

PMID- 8267682
TI  - Mammalian cell cultures. Part I: Characterization, morphology and metabolism.
AB  - Primary cell cultures are obtained by trypsinization from tissue cultures usually
      as a monolayer culture. The absence of fetal calf serum will support suspended
      growth behaviour of spontaneously transformed cells. After several passages the
      cell line becomes more stable and gives rise to a continuous cell line. Such
      continuously growing cell lines are a prerequisite for production of recombinant
      DNA derived proteins. Mammalian cells are 10-100 times larger in diameter than
      microorganisms. They have no cell wall and express therefore a higher sensitivity
      to hydrodynamic sheer forces. One of the most stringent problems in mammalian
      cell culture are "silent" contaminants with mycoplasma which might change cell
      growth. Mammalian cell cultures show a complex metabolism where regulation of
      metabolites and catabolites are not fully understood. Glucose is the main
      carbohydrate source. Also three groups of intercorrelated amino acids are known.
      Lactate as the primary metabolite of glucose and ammonia as a metabolite of
      glutamine are expected to be cytotoxic for mammalian cells. Although in some
      experiments even the addition of ammonia has no significant effect on the
      viability of hybridoma cells. Adherent cells can be cultivated attached to
      surfaces such as microcarrier or wire springs. Suspended cells are grown in
      stirred bioreactors with a comparable technology to fermentation of
      microorganism. Parameters such as pH, temperature, stirring tip speed and
      osmolality have to be well controlled in order to obtain high cell viability and
      cell density.

PMID- 8267683
TI  - Retroperitoneal laparoscopic nephrectomy: initial case report.
AB  - Pre-transplant nephrectomy was done in a 25-year-old man for calculous
      pyelonephritis using a retroperitoneal laparoscopic approach with a newly devised
      ligature applicator-dissector- kidney retractor.

PMID- 8267684
TI  - Penile vascular evaluation of men with Peyronie's disease.
AB  - A penile vascular evaluation was performed upon 95 consecutive men with
      Peyronie's disease (19 potent and 76 impotent) and 100 consecutive impotent men
      without Peyronie's disease to gain further understanding of the pathophysiology
      of erectile dysfunction in patients with Peyronie's disease. Only 1 of the 19
      potent patients with Peyronie's disease had abnormal arterial blood flow by
      duplex ultrasonography and none had evidence of veno-occlusive dysfunction by
      either duplex ultrasonography or dynamic infusion cavernosometry/cavernosography.
      In contrast, 36% of the impotent men with Peyronie's disease had abnormal
      arterial blood flow and 59% had evidence of veno-occlusive dysfunction. There was
      no significant difference in historical risk factors for impotence between the
      impotent patients with Peyronie's disease and the control population of impotent
      patients. However, the presence of veno-occlusive dysfunction in the control
      population (16%) was significantly less than that of the impotent Peyronie's
      disease patients (p < 0.001). Although patients with Peyronie's disease may
      suffer impotence due to arterial occlusive disease, our results indicate that the
      principal cause of impotence in this patient population is veno-occlusive
      dysfunction.

PMID- 8267685
TI  - Visualization of the thymus with therapeutic doses of radioiodine in patients
      with thyroid cancer.
AB  - Two cases of papillary carcinoma of the thyroid are presented in which whole-body
      scans following therapeutic doses of iodine-131 revealed intense anterior
      mediastinal uptake. In both cases, the mediastinal uptake was absent from scans
      obtained after removal of the entire thymus. Histologically, the resected thymus
      glands showed hyperplasia and contained neither thyroid tissue nor metastatic
      foci of thyroid carcinoma. We therefore concluded that anterior mediastinal
      uptake of radioiodine may be caused by hyperplasia of the thymus.

PMID- 8267686
TI  - Percutaneous endoscopic discectomy: surgical technique and preliminary results
      compared to microsurgical discectomy.
AB  - Percutaneous endoscopic discectomy is a new technique for removing "contained"
      lumbar disc herniations (those in which the outer border of the anulus fibrosus
      is intact) and small "noncontained" lumbar disc herniations (those at the level
      of the disc space and occupying less than one-third of the sagittal diameter of
      the spinal canal) through a posterolateral approach with the aid of specially
      developed instruments. The technique combines rigid straight, angled, and
      flexible forceps with automated high-power suction shaver and cutter systems.
      Access can thus be gained to the dorsal parts of the intervertebral space where
      the disc herniation is located. Percutaneous endoscopic discectomy is monitored
      using an endoscope angled to 70 degrees coupled with a television and video unit
      and is performed with the patient under local anesthesia and an anesthesiologist
      available if needed. Its indication is restricted to discogenic root compression
      with a minor neurological deficit. Two groups of patients with contained or small
      noncontained disc herniations were treated by either percutaneous endoscopic
      discectomy (20 cases) or microdiscectomy (20 cases). Both groups were
      investigated in a prospective randomized study in order to compare the efficacy
      of the two methods. The disc herniations were located at L2-3 (one patient), L3-4
      (two patients), or L4-5 (37 patients). There were no significant differences
      between the two groups concerning age and sex distribution, preoperative
      evolution of complaints, prior conservative therapy, patient's occupation,
      preoperative disability, and clinical symptomatology. Two years after
      percutaneous endoscopic discectomy, sciatica had disappeared in 80% (16 of 20
      patients), low-back pain in 47% (nine of 19 patients), sensory deficits in 92.3%
      (12 of 13 patients), and motor deficits in the one patient affected. Two years
      after microdiscectomy, sciatica had disappeared in 65% (13 of 20 patients), low
      back pain in 25% (five of 20 patients), sensory deficits in 68.8% (11 of 16
      patients), and motor deficits in all patients so affected. Only 72.2% of the
      patients in the microdiscectomy group had returned to their previous occupation
      versus 95% in the percutaneous endoscopic discectomy group. Percutaneous
      endoscopic discectomy appears to offer an alternative to microdiscectomy for
      patients with "contained" and small subligamentous lumbar disc herniations.

PMID- 8267687
TI  - Comparison of closed and open kinetic chain exercise in the anterior cruciate
      ligament-deficient knee.
AB  - The purpose of this study was to quantify the amount of anterior tibial
      displacement occurring in anterior cruciate ligament-deficient knees during two
      types of rehabilitation exercises: 1) resisted knee extension, an open kinetic
      chain exercise; and 2) the parallel squat, a closed kinetic chain exercise. An
      electrogoniometer system was applied to the anterior cruciate ligament-deficient
      knee of 11 volunteers and to the uninvolved normal knee in 9 of these volunteers.
      Anterior tibial displacement and the knee flexion angle were measured during each
      exercise using matched quadriceps loads and during the Lachman test. The anterior
      cruciate ligament-deficient knee had significantly greater anterior tibial
      displacement during extension from 64 degrees to 10 degrees in the knee extension
      exercise as compared to the parallel squat exercise. In addition, the amount of
      displacement during the Lachman test was significantly less than in the knee
      extension exercise, but significantly more than in the parallel squat exercise.
      No significant differences were found between measurements in the normal knee. We
      concluded that the stress to the anterior cruciate ligament, as indicated by
      anterior tibial displacement, is minimized by using the parallel squat, a closed
      kinetic chain exercise, when compared to the relative anterior tibial
      displacement during knee extension exercise.

PMID- 8267688
TI  - Disk-caused nerve compression in patients with acute low-back pain: diagnosis
      with MR, CT myelography, and plain CT.
AB  - Ninety-five patients with acute low-back and radicular pain underwent magnetic
      resonance (MR) imaging and either plain computed tomography (CT) (n = 32) or CT
      myelography (n = 63) for diagnosis of herniated nucleus pulposus-caused nerve
      compression (HNPNC). Patients were followed up for at least 6-12 months. Fifty
      six patients underwent surgery, and 39 received conservative treatment. Receiver
      operating characteristic (ROC) analysis was performed on correlation of results
      of blinded image reading with "true" diagnoses determined by an expert panel
      [corrected]. Results in subgroup analysis for ROC curve areas were MR, 0.84,
      versus plain CT, 0.86; MR, 0.81, versus CT myelography, 0.83; and MR, 0.82,
      versus findings with both CT techniques, 0.85. Results indicate no statistically
      significant difference in diagnostic accuracy of HNPNC among the three
      modalities. Thus, factors of cost, radiation dose, and invasiveness influence
      selection of modality. On the basis of accuracy findings, the authors suggest
      that MR should replace CT myelography because of the invasiveness of myelography
      but that MR should not replace plain CT because plain CT is equally accurate and
      much less costly.

PMID- 8267689
TI  - A method to assess the trainee profiles of medical students attracted to our
      physical medicine and rehabilitation residency training program.
AB  - A 35-item questionnaire was designed to assess the relative importance of various
      factors to medical students when ranking physical medicine and rehabilitation
      (PM&R) residency training programs. The questionnaire was used to assess the
      relative importance of the various factors to three groups of medical students:
      those who interviewed, those who matched and those who were listed on the match
      list of the UMDNJ-New Jersey Medical School (NJMS) Department of PM&R, as well as
      our current residents. Recipients were asked to grade selection factors based on
      a numerical scale: 1, extremely important; 2, very important; 3, important; 4,
      minimally important; 5, not important. A response rate of 100% (n = 72 medical
      students + 25 residents) was attained. The analysis indicates that, overall,
      there is no significant difference in ranking of the factors by each of the four
      groups. However, the medical students who recently matched with the UMDNJ-NJMS
      PM&R program rated the opportunity to conduct research significantly higher than
      the current house staff or the medical students on the entire match list. This is
      a desirable result, as the program strives to provide an environment that is
      conducive to the growth of research and academic physiatrists. This questionnaire
      could also be used by other residency training directors to guide the development
      of their program and to gain valuable information regarding the perception of
      their program among in-coming residents and the importance of various factors to
      the students interested in their program.

PMID- 8267690
TI  - Progression to diabetes in nonobese diabetic (NOD) mice with transgenic T cell
      receptors.
AB  - The T cell receptor (TCR) requirements in the pathogenesis of insulin-dependent
      diabetes were examined with transgenic NOD mice bearing nondisease-related TCR
      alpha and beta chains. In both TCR beta and TCR alpha beta transgenic NOD mice
      the beta chain transgene was expressed by > 98% of peripheral T cells. The alpha
      chain transgene was also highly expressed. Insulitis developed in both sets of
      transgenic animals with most of the lymphocytes in the lesion expressing the
      transgenic beta chain and with depletion of the endogenous TCR V beta genes.
      Nonetheless, NOD animals transgenic for TCR beta and TCR alpha beta developed
      diabetes similar to controls. Thus, skewing the TCR repertoire did not diminish
      autoimmune susceptibility in NOD mice.

PMID- 8267691
TI  - Nutrition management of insulin-dependent diabetes mellitus in adults: review by
      the diabetes care and education dietetic practice group.
AB  - Insulin-dependent diabetes mellitus (IDDM) is a chronic disease in which insulin
      production from the pancreas is diminished or absent. Insulin-dependent diabetes
      mellitus is most often diagnosed in childhood, but it also occurs in adults.
      Treatment requires the use of exogenous insulin coordinated with food intake and
      physical activity. Management goals for IDDM are to attain metabolic control of
      glucose and lipid levels and to prevent or delay the onset of medical
      complications associated with diabetes. Because the type and amount of food
      consumed directly affect blood glucose levels, meal and snack planning, along
      with an appropriate insulin regimen and physical activity program, is necessary
      to achieve management goals. Nutrition assessment, initial education,
      implementation of a meal plan, and ongoing nutrition education and counseling are
      part of the process of nutrition management of diabetes. The registered dietitian
      who has a working knowledge of nutrition and diabetes management serves as an
      integral part of the diabetes health care team.

PMID- 8267692
TI  - Protective effect of loratadine on late phase reaction induced by conjunctival
      provocation test.
AB  - The protective effect of Loratadine, a new generation, non-sedating
      antihistamine, on clinical and cellular events during the early phase reaction
      (EPR) and late phase reaction (LPR) of the allergen-specific conjunctival
      provocation test (CPT) was assessed out of the pollen season in 20 seasonally
      allergic rhino-conjunctivitis patients. After a screening CPT, selected patients
      were randomized to Loratadine (10 mg OD) or matching placebo for 7 days. CPT was
      repeated following treatment. Clinical and cellular responses were evaluated by a
      symptom score and cell counting in conjunctival scrapings before, and 30 min and
      6 h after challenge with allergen (one eye) or placebo (control eye).
      Conjunctival symptom severity following CPT was reduced at 30 min (EPR) and 6 h
      (LPR) after CPT in the Loratadine group compared to placebo group (p < 0.01), as
      was the total number of inflammatory cells (p < 0.001). In conclusion, Loratadine
      protects against the clinical and cellular EPR and LPR events consequent to CPT,
      showing antiallergic properties.

PMID- 8267693
TI  - Angiotensin-converting enzyme inhibitors as possible exacerbating drugs in
      psoriasis.

PMID- 8267694
TI  - Early detection of primary cytomegalovirus infection after heart and kidney
      transplantation and the influence of hyperimmune globulin prophylaxis.
AB  - A randomized study of prophylaxis with hyperimmune globulin (HIg) was performed
      in 28 cytomegalovirus (CMV)-seronegative heart and kidney recipients with CMV
      seropositive donors who were extensively monitored for active CMV infection and
      CMV disease. Detection of CMV antigen in peripheral blood granulocytes
      (antigenemia) was the first sign of primary CMV infection, generally occurring
      several weeks before IgM or IgG anti-CMV antibodies were detected and before
      positive cultures appeared. A correlation was found between rejection treatment
      with OKT3 or ATG, severity of CMV disease, and graft loss. Rejection treatment
      had no influence on incidence of CMV transmission. Primary CMV infection occurred
      most often in older patients with older donors. No beneficial effects were seen
      with HIg prophylaxis, which was administered from week 1 until week 7 after
      transplantation. Incidence of primary CMV infection was equal in both groups
      (50%) and no influence on the severity of primary CMV infection was seen. The
      only effect that was seen was on the time from transplantation to detection of
      active CMV infection, which was prolonged by HIg prophylaxis.

PMID- 8267695
TI  - Aminoglycoside dosing considerations in intensive care unit patients.
AB  - OBJECTIVE: Factors affecting aminoglycoside dosing requirements in critically ill
      adult patients were reviewed. DATA SOURCES: A literature search was performed
      from 1979 to 1992 and articles pertaining to aminoglycoside dosing were obtained.
      STUDY SELECTION: Only studies appearing in peer-reviewed journals were selected.
      Topics selected included: bactericidal kill kinetics, once-daily dosing regimens,
      critical illness, toxicity, aminoglycosides, intensive care unit, and lung
      penetration. CONCLUSIONS: Studies suggest that larger initial aminoglycoside
      doses are necessary in critically ill patients (tobramycin/gentamicin 3 mg/kg or
      amikacin 9 mg/kg) to achieve adequate peak serum concentrations. Current studies
      have not shown an increase in the incidence of aminoglycoside toxicity when using
      these larger initial doses. Follow-up monitoring is dependent upon the patient's
      physiology and risk factors for aminoglycoside-induced toxicity.

PMID- 8267696
TI  - Gastrointestinal metastases of breast carcinoma.

PMID- 8267697
TI  - Initiation and management of insulin pump therapy.
AB  - Insulin infusion pump therapy is a treatment option that facilitates achieving
      improved blood glucose control and lifestyle flexibility. These advantages are
      derived from the physiologic mode of insulin delivery and the pharmacologic
      advantages of using rapid-acting insulin. Patients who are sufficiently motivated
      and capable can learn to use the pump so that insulin adjustments can be made to
      compensate for changing circumstances. Although there are potential risks and
      side effects of using an insulin pump, these can be avoided through proper
      education and surveillance. The health care provider should be knowledgeable
      about the management of infusion pump therapy, including assessment of patient
      capabilities and practices, education, insulin adjustment, and techniques of use.
      The knowledge assists the health care provider in counseling patients to consider
      pump therapy and to manage patients already employing this mode of insulin
      delivery.

PMID- 8267698
TI  - Politics of rural health care: recruitment and retention of physicians.
AB  - The shortage of physicians in underserviced areas has been defined, and the
      causative recruitment and retention factors have been identified. The CMA report
      provides a framework for understanding these factors. Many can be modified, but
      this requires cooperation between physicians, communities, hospitals, medical
      schools, medical associations and governments. The development of a rural
      practice master plan in each province would facilitate this process.

PMID- 8267699
TI  - Diagnostic dilatation and curettage.

PMID- 8267700
TI  - Maintenance of strength gains while performing endurance training in oarswomen.
AB  - This study investigated the retention of strength gained after resistance
      training, while performing aerobic endurance training. Following a 10-week
      resistance training program (three times a week) that included maintenance
      aerobic endurance training (twice a week), 18 varsity oarswomen were matched on
      strength and randomly assigned to two groups: Group 1 performed maintenance
      resistance training once a week and Group 2 performed resistance training twice a
      week. Both groups performed endurance training four times a week during the 6
      week maintenance resistance training program. There was a significant increase in
      strength (multiple-RM test) for three upper and three lower body exercises after
      the initial 10-week resistance training program. A further significant increase
      in two exercises (inclined leg press and knee flexion) were observed after 6
      weeks of maintenance resistance training and endurance training in both groups.
      No further significant increases were observed in the four other exercises during
      maintenance strength training. These latter findings occurred at the same time
      that VO2max and ventilation threshold increased. These results suggest that
      strength gains can be maintained with resistance training once or twice a week
      while focusing on improving aerobic endurance performance without compromising
      the latter.

PMID- 8267701
TI  - Anxiety and endocrine responses to surgery.

PMID- 8267702
TI  - Taking aim at firearm injuries.

PMID- 8267703
TI  - Osteopathic medicine: a call for reform.
AB  - During the past 40 years, the osteopathic medical profession has undergone a
      transformation from "osteopathy" to "osteopathic medicine." The former was
      characterized by manipulative treatment; the latter, by full-service healthcare.
      During this transformation, the profession has won acceptance from the
      government, the military, and MDs. These changes in status have resulted in new
      problems for the profession because DO graduates are increasingly turning toward
      allopathic programs for residency training. Thus, osteopathic medicine's primary
      care orientation is being replaced by an emphasis on specialty training. The
      authors propose that osteopathic medicine return to its original mission of
      primary care, abandon or restrict specialty training to those who have completed
      primary care residencies, and rethink its separate-but-equal posture. They also
      propose that osteopathic medicine establish lines of communication with
      allopathic medicine, the American Medical Association, and the government to
      facilitate the development of a rational national policy for primary care that
      considers the potential osteopathic medicine has to offer in meeting the nation's
      primary care needs.

PMID- 8267704
TI  - Number of pregnancies and the subsequent risk of cardiovascular disease.
AB  - BACKGROUND: Whether increasing parity or gravidity is a risk factor for coronary
      heart disease has been debated, but the question remains unresolved. METHODS: We
      tested the association between the number of pregnancies and a variety of
      cardiovascular end points in two groups of women who had completed childbearing.
      One group comprised 2357 women who were followed for 28 years through the
      Framingham Heart Study, and the other 2533 women followed for at least 12 years
      through the first National Health and Nutrition Examination Survey National
      Epidemiologic Follow-up Study (NHEFS). RESULTS: The rates of coronary heart
      disease were higher among multigravid women than among women who had never been
      pregnant, in both the Framingham Heart Study and the NHEFS, but in both studies,
      the higher rates were statistically significant only in women with six or more
      pregnancies. For the women in the Framingham Study, the rate ratio adjusted for
      age and educational level in the group with six or more pregnancies (as compared
      with women who had never been pregnant) was 1.6 (95 percent confidence interval,
      1.1 to 2.2). For the women in the NHEFS, the same adjusted rate ratio was 1.5 (95
      percent confidence interval, 1.1 to 1.9). Adjustments for other known
      cardiovascular risk factors, including weight, did not markedly alter this risk.
      The rate of total cardiovascular disease was also significantly higher among
      multigravid women in the Framingham Study than in the women who had never been
      pregnant. CONCLUSIONS: In two prospective American studies, having six or more
      pregnancies was associated with a small but consistent increase in the risk of
      coronary heart disease and cardiovascular disease. Whether gravidity itself or
      some other unmeasured factor accounts for the increase in risk that we observed
      requires further investigation.

PMID- 8267705
TI  - Informed consent and use of artificial baby milk.

PMID- 8267706
TI  - Myocardial scintigraphy with iodine-123 phenylpentadecanoic acid and thallium-201
      in patients with coronary artery disease: a comparative dual-isotope study.

PMID- 8267707
TI  - Death by reverse suspension.

PMID- 8267708
TI  - Special needs of elderly diabetic patients.

PMID- 8267709
TI  - Clinical application of pulse oximetry.
AB  - Pulse oximetry has become a common monitoring tool in critical care units over
      the past few years. But, as sometimes happens with new technology, use of the
      equipment can precede solid education about the applications and limitations of
      the device and how values should be interpreted.

PMID- 8267710
TI  - Predicting the future of HIV/AIDS nursing.

PMID- 8267711
TI  - NSAIDs and postoperative pain.

PMID- 8267712
TI  - Examination of cell toxicity and dosing regimen in an in vitro chromosomal
      aberration assay.

PMID- 8267713
TI  - Postpartum herbal care.

PMID- 8267714
TI  - Polyamine-phospholipid complex blocks NMDA-activated currents in vitro.

PMID- 8267715
TI  - A novel programed frameshift expresses the POL3 gene of retrotransposon Ty3 of
      yeast: frameshifting without tRNA slippage.
AB  - Most retroviruses and retrotransposons express their pol gene as a translational
      fusion to the upstream gag gene, often involving translational frameshifting. We
      describe here an unusual translational frameshift event occurring between the
      GAG3 and POL3 genes of the retrotransposon Ty3 of yeast. A +1 frameshift occurs
      within the sequence GCG AGU U (shown as codons of GAG3), encoding alanine-valine
      (GCG A GUU). Unlike other programed translational frameshifts described, this
      event does not require tRNA slippage between cognate or near-cognate codons in
      the mRNA. Two features distal to the GCG codon stimulate frameshifting. The low
      availability of the tRNA specific for the "hungry" serine codon, AGU, induces a
      translational pause required for frameshifting. A sequence of 12 nt distal to the
      AGU codon (termed the Ty3 "context") also stimulates the event.

PMID- 8267716
TI  - Opioid addiction in anesthesiology.

PMID- 8267717
TI  - Acute circulatory support.
AB  - Numerous drugs can increase cardiac output, thereby improving tissue oxygen
      delivery, but often they do this at the expense of increasing myocardial oxygen
      demand. This may be critical when cardiac function is substantially impaired or
      ischaemia is the precipitating cause. Using polypharmacy to substantially improve
      cardiovascular status requires detailed knowledge of the pharmacodynamics and
      interactions of the available agents so that they may be tailored to the
      individual patient. In some settings combinations of inotropes and vasodilators
      may be desirable to minimise cardiac workload. In other instances vasopressors
      may be necessary to urgently restore a minimum perfusion pressure. This paper
      reviews the use of this group of drugs as well as the mechanical assist devices
      that may be used when drugs fail.

PMID- 8267718
TI  - Assessing GPs' performance. Videotape assessment is threatening.

PMID- 8267719
TI  - Improving the sexual health of the nation.

PMID- 8267720
TI  - Re: Abernathy TJ, Bertrand LD. Preventing cigarette smoking among children:
      results of a four-year evaluation of the PAL program.

PMID- 8267721
TI  - Ceftriaxone for otitis media.

PMID- 8267722
TI  - The discovery of the cardiac conduction system.

PMID- 8267723
TI  - Opioids and cerebral blood flow velocity.

PMID- 8267724
TI  - Transient bullous dermolysis of the newborn: new pathologic findings.

PMID- 8267725
TI  - Acoustic neuroma: triumphs outnumber the disasters.

PMID- 8267726
TI  - Rural health care.

PMID- 8267727
TI  - Community care for the elderly.

PMID- 8267728
TI  - Contact sensitivity to N-A dressing.

PMID- 8267729
TI  - The fatal paracetamol dosage--how low can you go?

PMID- 8267730
TI  - Right ventricular infarction.

PMID- 8267731
TI  - Meningiomas involving the clivus: a six-year experience with 41 patients.

PMID- 8267732
TI  - Patient information.

PMID- 8267733
TI  - Immunoglobulin-related amyloidosis presenting as recurrent isolated lymph node
      involvement.

PMID- 8267734
TI  - Comment on the Nottingham Prognostic Index.

PMID- 8267736
TI  - Nature in your birth bag.

PMID- 8267735
TI  - NSAIDS in the postoperative period. Use with caution in elderly people.

PMID- 8267737
TI  - I recommended the use of sassafrass tea postpartum to help combat mastitis.

PMID- 8267738
TI  - Mediastinal uptake of 131-I in patients with thyroid cancer: may it be referred
      to normal thymus?

PMID- 8267739
TI  - Molecular constructivity.

PMID- 8267740
TI  - Implant failures.

PMID- 8267741
TI  - Incompatibility of papaverine with various intravascular contrast agents.

PMID- 8267742
TI  - Earliest electrocardiographic evidence of myocardial infarction: implications for
      thrombolytic treatment. The GREAT Group.
AB  - OBJECTIVES: To determine the incidence of the earliest electrocardiographic
      changes in patients with suspected myocardial infarction and their sensitivity
      and specificity for predicting the final diagnosis of acute myocardial
      infarction. DESIGN: Retrospective study of paired electrocardiograms recorded at
      home and on admission to hospital. SETTING: 29 rural practices in Grampian and
      teaching hospitals in Aberdeen. PATIENTS: 137 patients participating in the early
      anistreplase trial in the Grampian region, who received placebo at home and for
      whom paired electrocardiograms were available. MAIN OUTCOME MEASURES: Classified
      electrocardiographic abnormalities and diagnosis at discharge. RESULTS:
      Electrocardiograms were recorded immediately before injection of placebo at home
      and anistreplase in hospital at median times of 110 and 240 minutes after the
      onset of symptoms. Definite or probable myocardial infarction was later confirmed
      in 93 (68%) patients. Of these, 66 (71%) had the same findings on both
      electrocardiograms of either ST elevation, bundle branch block, or a non-specific
      abnormality, while 27 (29%) showed a major change of classification between home
      and hospital recordings; 21 (23%) had ST elevation or bundle branch block on only
      one of the paired recordings. Although ST elevation was the commonest abnormality
      in the 93 patients with myocardial infarction, in only 51 was it recorded at home
      (sensitivity 55%) and in 49 on admission (sensitivity 53%). Of 57 patients with
      ST elevation at home, six did not have infarction (specificity 86%), while of 51
      with ST elevation on admission, two did not have infarction (specificity 95%).
      CONCLUSIONS: Elevation of the ST segment is a transient electrocardiographic
      abnormality that has high specificity but low sensitivity for predicting the
      diagnosis of acute myocardial infarction; it is an unsatisfactory precondition
      for giving thrombolytic treatment to patients with suspected acute myocardial
      infarction.

PMID- 8267743
TI  - High dose inotropic support in septic shock.

PMID- 8267744
TI  - Prognostic factors for patients with Hodgkin disease in first relapse.

PMID- 8267745
TI  - Utility of unconjugated estriol in screening for Down syndrome is not proven.

PMID- 8267746
TI  - Mucin inclusions in urothelial carcinomas.

PMID- 8267747
TI  - Endoscopic management of uterine perforation occurring during endometrial
      resection.

PMID- 8267748
TI  - Prostaglandin prophylaxis and bladder function after vaginal hysterectomy: a
      prospective randomized study.

PMID- 8267749
TI  - Sexual health. Medical training must acknowledge sexuality.

PMID- 8267750
TI  - Serum screening for Down's syndrome. Existing tests not good enough.

PMID- 8267751
TI  - Sialic acid and heart disease.

PMID- 8267752
TI  - Acute circulatory support. Dopamine's renal effects are complex.

PMID- 8267753
TI  - Prescribing costs. Weighting allowance insufficient.

PMID- 8267755
TI  - Menopause: another stage of labor.

PMID- 8267754
TI  - Tumour suppressor genes and risk of metastasis in ovarian cancer.

PMID- 8267756
TI  - Surgical anatomy of the dog.

PMID- 8267757
TI  - Prospective randomized comparison of in situ and reversed infrapopliteal vein
      grafts.

PMID- 8267758
TI  - Penetrating external injuries of the oesophagus and pharynx.
AB  - Fifty-one instances of oesophageal perforation were discovered when the records
      of 10,143 [corrected] patients with external penetrating injuries of the neck,
      chest and abdomen were reviewed. Of these, 33 resulted from stab wounds, 17 from
      bullets and one from hyperextension of the neck. There were 15 perforations of
      the pharynx and 36 of the oesophagus. Oesophagography in a lateral decubitus
      position demonstrated the perforation in all 16 patients in whom it was used. In
      45 patients simple repair within 24 h of injury was performed (mortality rate 11
      per cent). In six patients with a delay of more than 24 h in the repair of the
      thoracic oesophagus, special techniques were preferred. In two patients an
      oesophageal diversion-exclusion method was used; one such patient died. In four
      patients repair over a large-bore T tube was carried out with one death. The main
      cause of mortality was associated spinal injury (four deaths).

PMID- 8267759
TI  - LMA for failed intubation.

PMID- 8267760
TI  - Comment on ASHP therapeutic guidelines.

PMID- 8267761
TI  - Neuronal protection against excitotoxicity.

PMID- 8267762
TI  - ATLS and the Gulf War.

PMID- 8267763
TI  - Pregnancy and plastic surgery residency.

PMID- 8267764
TI  - Intraoral versus intranasal approach to lateral osteotomy.

PMID- 8267765
TI  - Effect of milrinone in human platelet shape change, aggregation and thromboxane
      A2 synthesis: an in vitro study.
AB  - Milrinone (MIL; a cAMP-specific phosphodiesterase type-III inhibitor), added in
      vitro to achieve concentrations below the therapeutic levels, inhibited agonist
      induced platelet shape change (PSC). Arachidonic acid (AA)-induced PSC was
      significantly more inhibited by a combination of MIL and indomethacin (INDO; a
      cyclooxygenase inhibitor) than by either alone. PSC induced by 5
      hydroxytryptamine was inhibited by MIL but not by INDO; and this effect of MIL
      was not augmented by INDO. Whole blood-platelet aggregation (WB-PA) and platelet
      rich plasma aggregation induced by potent stimulators of thromboxane A2 (TXA2)
      synthesis such as AA and calcium ionophore and by less potent agonists (e.g. ADP
      and U46619) were inhibited by MIL at or near therapeutic concentrations. WB-PA
      induced by collagen was significantly more inhibited by the MIL and INDO
      combination than by either of these agents alone whereas with ADP-induced WB-PA
      no additional effect could be shown when both MIL and INDO were co-incubated. MIL
      and similar types of drugs may be of benefit in conditions associated with
      platelet hyperactivity and some of these effects may be enhanced by
      cyclooxygenase inhibitors.

PMID- 8267766
TI  - Prognostic implications of age.

PMID- 8267767
TI  - Enhancing factor, a Paneth cell specific protein from mouse small intestines:
      predicted amino acid sequence from RT-PCR amplified cDNA and its expression.
AB  - Enhancing factor (EF), a Paneth cell specific growth factor modulator, has been
      identified in our laboratory from mouse small intestines. In this paper we
      describe generation of an EF specific cDNA by RT-PCR and its sequence. The
      predicted amino acid sequence was found to be similar to, and hence confirms, the
      partial amino acid sequence obtained earlier by protein sequencing. In Northern
      blot analysis, a 1 kb transcript was observed in intestinal RNA alone. In situ
      hybridization indicated that the EF gene is expressed exclusively in the Paneth
      cells. The present study indicates that EF is an isoform of PLA2 type II, with a
      unique tissue distribution, found predominantly in the Paneth cells of the small
      intestines. Further, based on the properties of EF, we propose that isoforms of
      PLA2, belonging to type II, may be involved in regulation of cell proliferation
      via EGF binding.

PMID- 8267768
TI  - Deciding who needs thrombolysis. Don't rush to widen criteria.

PMID- 8267769
TI  - Deciding who needs thrombolysis. Acronyms must be explained.

PMID- 8267770
TI  - Practical guidelines for tuberculosis control.  World Health Organization, the
      International Union Against Tuberculosis and Lung Disease and the Centers for
      Disease Control, USA.

PMID- 8267771
TI  - Pneumatic retinopexy with air.

PMID- 8267772
TI  - Adult respiratory distress syndrome and lung transplantation.

PMID- 8267773
TI  - Comments on "Complications of endomyocardial biopsy in heart transplant
      patients".

PMID- 8267774
TI  - Psychological distress and preterm delivery. Unconvincing link.

PMID- 8267775
TI  - Hyperbaric oxygen. Still unproved in necrotising fasciitis.

PMID- 8267776
TI  - Microalbuminuria in chronic obstructive lung disease. Multiple urine samples
      should be timed.

PMID- 8267777
TI  - Natural family planning. Couples take chances.

PMID- 8267778
TI  - Near patient testing. Needs quality control.

PMID- 8267780
TI  - Biblical leprosy.

PMID- 8267779
TI  - Cell and heparin binding in the distal long arm of laminin: identification of
      active and cryptic sites with recombinant and hybrid glycoprotein.
AB  - The long arm of laminin, which binds heparin and cells, consists of three
      polypeptides (A, B1, and B2) joined in a coiled-coil rod attached to a terminal A
      chain globule (G). Previously, we found that recombinant globular domain (rG)
      supported heparin and myoblast binding (Yurchenco, P. D., U. Sung, M. D. Ward, Y.
      Yamada, and J. J. O'Rear. 1993. J. Biol. Chem. 268:8356-8365). To further analyze
      long arm functions, we expressed the distal moiety of the mouse laminin A chain
      extending from the middle of the rod to the carboxyl terminus (rAiG). This larger
      glycoprotein, secreted by Sf9 insect cells infected with recombinant baculovirus,
      was intercalated in vitro into the corresponding disulfide-linked B chain
      segments of laminin fragment E8 (distal long arm rod and proximal globule). The
      hybrid molecule (B-rAiG) possessed a structure similar to laminin long arm as
      judged by electron microscopy and limited proteolysis. By joining rAiG with E8-B
      chains, the affinity of G domain for heparin decreased from that observed with
      rAiG and rG to one similar to native protein. HT1080 cells adhered to E8, rAiG,
      and B-rAiG, less well to rG, and not to denatured E8/B-rAiG, the A and B chain
      moieties of E8, or to a mixture of rG and E8-B chains. Cell adhesion to E8 and B
      rAiG, in contrast to rAiG, was inhibited with antibodies specific for alpha 6 and
      beta 1 integrin chains. Since intercalation (a) restored a conformationally
      dependent alpha 6 beta 1 integrin recognition site present in native protein, (b)
      inactivated a cryptic cell binding activity in the A chain, and (c) inhibited a
      heparin binding site present in proximal G domain, we conclude that biological
      activities of laminin are different from that of its isolated subunits.

PMID- 8267781
TI  - Esophageal ulcers as presenting features of human immunodeficiency virus disease.

PMID- 8267782
TI  - Number of pregnancies and risk of cardiovascular disease.

PMID- 8267783
TI  - HOM: concerns and limitations.

PMID- 8267784
TI  - T cell receptor specificity and diabetes in nonobese diabetic mice.

PMID- 8267785
TI  - Suicide and the military justice system.

PMID- 8267786
TI  - Catheter-related septicemia.

PMID- 8267787
TI  - Transverse sinus by TEE.

PMID- 8267788
TI  - Regional techniques in the asthmatic patient.

PMID- 8267789
TI  - Clostridium difficile-related disease: evaluation and prevalence among inpatients
      with diarrhea in two freestanding rehabilitation hospitals.
AB  - Clostridium difficile has been associated with diarrhea in hospitalized patients
      receiving antibiotic therapy, and may be nosocomially acquired. Rehabilitation
      hospital inpatients may require frequent antibiotic intervention and are thus at
      risk, though few reports of epidemics at such centers have been published. This
      study describes the evaluation and prevalence of C difficile-related disease,
      among rehabilitation hospital inpatients. A retrospective review was conducted of
      all diarrhea evaluations performed among inpatients in two freestanding
      rehabilitation hospitals over a two-year period. A total of 303 laboratory tests
      were performed among the 115 patients evaluated. C difficile was determined to be
      the etiologic agent of diarrhea in 25% of patients undergoing enteric evaluation,
      and in 39% of patients specifically assayed for C difficile toxin B. Giardiasis
      was detected in one patient, and no evidence of Salmonella, Shigella,
      Campylobacter, or Yersinia infection was found. The estimated prevalences for
      diarrhea and C difficile-related disease were 3.7% and 1.1%, respectively. Thus,
      C difficile is an important cause of diarrhea among rehabilitation hospital
      inpatients, though its true prevalence may be underestimated due to inadequate
      diagnostic evaluation. Enteric bacterial pathogens such as Campylobacter,
      Salmonella, Shigella, Yersinia, and Giardia are insignificant causes of diarrhea
      among these patients. Elimination of routine testing for these pathogens would
      reduce costs without compromising diagnostic utility. Diagnostic evaluation
      should include C difficile toxin assay, and if positive, appropriate therapy
      instituted.

PMID- 8267790
TI  - Haplotypic variation of the transporter associated with antigen processing (TAP)
      genes and their extension of HLA class II region haplotypes.
AB  - Stable cell surface presentation of HLA class I molecules requires active
      transport of antigenic peptides across the endoplasmic reticulum by products of
      two genes, TAP1 and TAP2, which map in the major histocompatibility complex class
      II region. Alleles of each gene are derived from a combination of variable sites
      at each locus. In this study, TAP1 and TAP2 alleles were identified in homozygous
      typing cell (HTC) lines, allowing resolution of specific haplotypes in
      conjunction with the highly polymorphic HLA class II region haplotypes. Three
      alleles at each TAP locus were found from which eight haplotypes could be
      assigned. Determination of TAP1 and TAP2 alleles in cell lines homozygous at DR,
      DQ, and DP created eight additional haplotypes beyond the number observed with
      these class II genes alone. Complete analysis of DR, DQ, TAP, and DP genotypes in
      66 HTCs resulted in the following groups: 1) 46 homozygotes; 2) nine homozygous
      at DR, DQ, and TAP, but heterozygous at DP; 3) four homozygous at DR, DQ, and DP,
      but heterozygous at one or both TAP genes; 4) four homozygous at DR and DQ, but
      heterozygous at TAP and DP; and 5) three complex genotypes heterozygous at DP,
      TAP, and at least one of DQA1, DQB1, or DRB1 loci. TAP1 and TAP2 genes map in an
      area of frequent recombination. TAP alleles were determined in five DQB1, DPB1
      recombinant individuals, three of which were informative. Recombination was found
      between DQB1 and the TAP loci in two individuals and between TAP and DPB1 in the
      other individual.

PMID- 8267791
TI  - Pradimicin S, a new pradimicin analog. II. Isolation and structure elucidation.
AB  - Pradimicin S was isolated from the culture filtrate of Actinomadura spinosa
      AA0851. NMR and MS analyses proved that pradimicin S is the 3'-O-(3''-O-sulfo
      beta-D-glucopyranosyl) analog of pradimicin A, a new member of the pradimicin
      family of antibiotics. Stereochemical assignment was made by correlating
      pradimicin S with pradimicin L.

PMID- 8267792
TI  - Inhibition of fibroblast and smooth muscle cell proliferation and migration in
      vitro by a novel aminochromone U-67154.
AB  - Medial smooth muscle cell migration and neointimal proliferation are primary
      contributors to the delayed restenosis that occurs after percutaneous
      transluminal coronary angioplasty. In this study, we describe the
      antiproliferative and antichemotactic properties of U-67154, the parent compound
      of a series of novel aminochromones, determined using in vitro fibroblast and
      smooth muscle cell culture systems. U-67154 inhibited the induction of DNA
      synthesis in confluent BALB/c 3T3 fibroblasts and early-passage rat aortic smooth
      muscle cells by several different growth factors in a concentration-dependent
      manner. U-67154 similarly inhibited the proliferation of these cells stimulated
      by serum. Growth-factor-induced chemotaxis of fibroblasts and early-passage rat
      aortic smooth muscle cells also was inhibited by U-67154 in a concentration
      dependent manner. The IC50s for all of these functions were similar (between 120
      and 200 microM). Such antiproliferative and antichemotactic effects did not
      result from cytotoxicity (as measured by lactate dehydrogenase release, neutral
      red uptake or nonspecific inhibition of protein synthesis). Most important,
      inhibition of long-term proliferation of fibroblasts and early-passage smooth
      muscle cells by U-67154 was fully reversible upon removal of the drug. Thus, U
      67154 represents a class of novel, noncytotoxic compounds that may prove useful
      in the treatment of proliferative disorders such as delayed restenosis after
      percutaneous transluminal coronary angioplasty.

PMID- 8267793
TI  - Defining E-cadherin-associated protein complexes in epithelial cells:
      plakoglobin, beta- and gamma-catenin are distinct components.
AB  - Ca(2+)-dependent cell adhesion is mediated by a family of proteins termed
      cadherins, and is modulated by cytosolic proteins that include alpha-, beta-, and
      gamma-catenin and other cytoskeletal proteins that bind to the cytoplasmic domain
      of cadherins. Recent studies have suggested that either beta- or gamma-catenin
      may be identical to plakoglobin, a protein associated with adherens junctions.
      However, the relationship between these proteins, and their interaction with
      cadherins, are not well understood. In this study, we have further defined the
      relationship between plakoglobin and the catenins in complexes with E-cadherin in
      Madin-Darby canine kidney (MDCK) cells. Specific immunoprecipitations revealed
      that plakoglobin (86 kDa) and beta-catenin (92 kDa) have different detergent
      extractabilities and apparent molecular weights in these cells; however,
      plakoglobin has an apparent molecular weight similar to that of gamma-catenin (86
      kDa). Immunoblotting of E-cadherin immunoprecipitates demonstrated that both
      plakoglobin and beta-catenin co-immunoprecipitate with E-cadherin. Laser-scanning
      confocal microscopy demonstrated temporally and spatially co-ordinate
      redistribution of plakoglobin and E-cadherin following induction of cell-cell
      contact in MDCK cells. Although plakoglobin comigrated with gamma-catenin on SDS
      PAGE, quantitative analysis of E-cadherin and plakoglobin immunoprecipitates
      revealed that plakoglobin accounted for < 50% of the gamma-catenin signal. Two
      dimensional gel electrophoresis resolved the gamma-catenin protein band into two
      proteins. One protein was identified as plakoglobin, based upon apparent
      molecular weight, immunoreactivity and isoelectric point (pI approximately 6.1).
      The other protein comigrated with gamma-catenin on SDS-PAGE, did not react with
      plakoglobin antibodies and had a pI of approximately 4.25; we refer to this
      protein as gamma-catenin to distinguish it from plakoglobin. Two-dimensional gel
      electrophoresis further revealed that plakoglobin comprised multiple isoelectric
      variants, but that, within the newly synthesized pool of plakoglobin, only the
      most basic of these variants co-immunoprecipitated with E-cadherin;
      phosphorylation did not account for the plakoglobin isoelectric variants seen by
      two-dimensional gel electrophoresis. These results demonstrate directly that
      plakoglobin associates and co-localizes with the E-cadherin in MDCK epithelial
      cells in a complex that contains alpha-, beta-, and gamma-catenin. Although
      plakoglobin shares sequence similarity with beta-catenin, and comigrates with
      gamma-catenin in SDS-PAGE, plakoglobin is distinct from the catenins. The
      association of plakoglobin with E-cadherin may be regulated by post-translational
      modifications of plakoglobin.

PMID- 8267794
TI  - Detection and identification of a chromophoric intermediate during the medium
      chain fatty acyl-CoA dehydrogenase-catalyzed reaction via rapid-scanning
      UV/visible spectroscopy.
AB  - We have investigated the medium-chain fatty acyl-CoA dehydrogenase (MCAD)
      catalyzed reaction via rapid-scanning stopped-flow (RSSF) UV/vis spectroscopy,
      combined with the single-wavelength stopped-flow technique, utilizing 3
      indolepropionyl-CoA (IPCoA) and trans-3-indoleacryloyl-CoA (IACoA) as
      chromophoric pseudosubstrates. The RSSF spectral data reveal that formation of an
      intermediary species with an absorbance maximum at 400 nm and a broad charge
      transfer band around 600 nm accompanies the reduction of MCAD-FAD by IPCoA. In
      the presence of high concentrations of enzyme ([MCAD] >> [IPCoA]) the
      intermediary spectral band at 400 nm remains unperturbed, whereas in the presence
      of low concentrations of enzyme ([MCAD] << [IPCoA]) it slowly shifts to an
      absorption band with an absorbance maximum at 370 nm. Appearance and
      disappearance of this intermediary species coincides with the appearance and
      disappearance of the charge-transfer band. Single-wavelength stopped-flow
      studies, performed under similar high and low enzyme conditions, were consistent
      with one (1/tau 1) and two (1/tau 1 > 1/tau 2) relaxation rate constants,
      respectively. These findings, combined with relaxation studies performed in the
      reverse directions as well as substrate and product binding studies with the
      oxidized and reduced forms of the enzyme, have allowed us to conclude the
      following: (1) the intermediary species possesses the properties of reduced
      flavin and highly conjugated reaction product IACoA (absorbance maximum = 400
      nm); (2) this intermediary species collapses into an MCAD-FADH2-IACoA complex
      (absorbance maximum = 370 nm) in the presence of excessive concentrations of
      IPCoA; the collapse is being driven by the competitive binding of IPCoA with the
      reduced form of the enzyme; (3) the 400-nm absorption band and the charge
      transfer band are given by the same intermediary species formed during the enzyme
      catalyzed reaction pathway. The role of protein conformational changes in
      modulating the substrate/product structures during the MCAD-catalyzed reaction is
      discussed.

PMID- 8267795
TI  - Interleukin 1 receptor antagonist inhibits the augmentation of metastasis induced
      by interleukin 1 or lipopolysaccharide in a human melanoma/nude mouse system.
AB  - This study examined the ability of the recombinant human interleukin 1 receptor
      antagonist (IL-1ra) to block interleukin 1 (IL-1)-mediated experimental
      metastases from the A375M human melanoma. In vivo, IL-1ra administrated at
      concentrations > or = 200 times IL-1 significantly inhibited the increase in lung
      colonies induced by IL-1 in nude mice. The response to IL-1 was significantly
      inhibited when IL-1ra was administered simultaneously with or 1 to 3 h before IL
      1. In vitro, the incubation of IL-1-activated endothelial cells with IL-1ra
      prevented the increase in adhesion of A375M melanoma cells. At the same
      experimental conditions, IL-1ra inhibited the augmented expression of the
      intracellular and vascular cell adhesion molecules 1 and E-selectin induced by IL
      1 on endothelial cells. Lipopolysaccharide, an IL-1 inducer, increased the number
      of lung colonies in nude mice. IL-1ra injected with or 1 h after
      lipopolysaccharide inhibited this augmentation, suggesting a role for host
      produced IL-1 in metastasis formation.

PMID- 8267796
TI  - The P-domain or trefoil motif: a role in renewal and pathology of mucous
      epithelia?
AB  - By analogy with epidermal growth factor and EGF-like repeats, the P-domain, or
      trefoil motif, is a characteristic shuffled module containing six invariant
      cysteine residues that forms the basic unit for a family of mucin-associated
      peptides. These P-domain peptides are potential modulators of cell growth and
      they are also expressed under certain pathological conditions. Furthermore, P
      domains have been found as components of extracellular mosaic proteins including
      certain mucins, where they are thought to play a role either in protein-protein
      or in lectin-like interactions.

PMID- 8267797
TI  - Applications of confocal microscopy to studies of sea urchin embryogenesis.

PMID- 8267798
TI  - [Study of a new endogenous inhibitor of enkephalin-degrading enzymes;
      pharmacological function and metabolism of spinorphin].
AB  - Spinorphin, a potent inhibitor of enkephalin degrading enzyme isolated from the
      bovine spinal cord, produces a dose-related inhibition of electrically evoked
      contractions of both MVD (mouse vas deferens) and GPI (guinea-pig ileum).
      Analgesic activity of Spinorphin was evaluated by the tail pinch method. The
      intraventricularly injected Spinorphin produced antinociceptive effect in a dose
      dependent manner, in dose of 50-200 micrograms.mouse-1. Most Spinorphin was
      degraded when incubated in the spinal cord for 24 hs. However, approximately 86%
      of the Spinorphin was intact on HPLC when incubated with probestin, which is an
      inhibitor of aminopeptidase-M. Spinorphin has a high inhibitory activity against
      enkephalin degrading enzymes when compared to the various hydrolysis products. In
      conclusion, the most important structure for enkephalin inhibitory activity in
      Spinorphin. It is suggested that Spinorphin acts as a neuromodulator of
      enkephalin metabolism in the spinal cord.

PMID- 8267799
TI  - Neonatal noma.
AB  - Neonatal noma is a rare clinical syndrome affecting term and preterm infants. It
      causes gangrene of the orofacial tissues accompanied by sepsis and a high
      mortality rate. A preterm 35-week infant, severely growth retarded in utero,
      developed clinical signs of sepsis with ulcers all over the oral mucosa caused by
      local infection with Pseudomonas aeruginosa. The lesions healed with cicatricial
      sequelae of the mouth, sequestration of teeth, and retraction of perimandibular
      soft tissues.

PMID- 8267800
TI  - Inadvertent amniocenteses occurring during unrelated invasive diagnostic
      procedures in the third trimester.
AB  - Two cases of inadvertent third trimester amniocenteses occurring during attempted
      spinal tap and culdocentesis are presented. These hitherto undescribed
      occurrences stress potential complications of these invasive diagnostic
      procedures in the gravid woman.

PMID- 8267802
TI  - Progression of nonimmune hydrops in a fetus with Noonan syndrome.
AB  - Presented is a case of nonimmune hydrops caused by Noonan syndrome. This
      autosomal dominant disorder, with an incidence of 1 in 1000 births, is manifested
      by trunk and limb edema, lymphatic abnormalities, webbed neck, short stature, and
      cardiac and genital anomalies. In this case the initial presentation was
      polyhydramnios at 31 weeks' gestation, followed in 1 week by pleural effusions
      and a week later by skin edema. An 18-week ultrasound had been normal. Because of
      variable expressivity, only the most severe cases of the disease are usually
      diagnosed. Thus, the incidence may be higher than 1 in 1000, and Noonan syndrome
      may be underdiagnosed as a cause of nonimmune hydrops. Since lymphedema in this
      syndrome may regress spontaneously, conservative obstetric management is
      preferable unless the fetus develops distress.

PMID- 8267801
TI  - Extensive fetal intrathoracic injuries sustained in a motor vehicle accident.
AB  - Motor vehicle accidents are the primary nonobstetric cause of maternal and
      subsequent fetal mortality. We present a case in which blunt abdominal trauma
      sustained by a pregnant woman in a motor vehicle accident caused extensive
      intrathoracic fetal injuries consisting of bilateral hemothorax, severe bilateral
      interstitial pulmonary hemorrhages, hemopericardium, and subepicardial
      hemorrhages, in addition to fetal cranial injuries. To the best of our knowledge,
      this is the first report of fetal intrathoracic injuries sustained with blunt
      maternal trauma. The underlying mechanism of intrathoracic trauma was thought to
      be similar to that of blast injury with transmission of excessive hydrostatic
      forces throughout the amniotic fluid with severe impact on the elastic fetal
      chest. This case supports the concept of in utero blast injury to the fetus as a
      possible cause for fetal soft tissue trauma associated with blunt trauma to the
      maternal abdomen.

PMID- 8267803
TI  - Massive pericardial effusion as a cause for sudden deterioration of a very low
      birthweight infant.
AB  - We describe the successful resuscitation of a very low birthweight infant after
      sudden deterioration caused by a massive pericardial effusion. The neonatal
      course of this 740 gm, 26-week gestational age infant had been complicated by
      moderate respiratory distress syndrome, apnea, and bronchopulmonary dysplasia. A
      Silastic catheter was placed percutaneously in the right axillary vein on day 6
      of life and documented to be in the superior vena cava prior to continuous
      parenteral nutrition. On day 38, her cardiorespiratory status abruptly
      deteriorated, blood return could not be obtained from the central line, and it
      was removed. Chest radiograph and subsequent echocardiogram confirmed a massive
      pericardial effusion. Under echocardiographic guidance, an emergency percutaneous
      pericardiocentesis allowed aspiration of 23 ml of straw-colored fluid. Her vital
      signs immediately returned to normal and reaccumulation of the effusion did not
      occur. Despite the high mortality of premature infants from pericardial effusion
      as a complication of central venous catheterization, early diagnosis and prompt
      therapy can assure a good outcome. As a cause of sudden deterioration of very low
      birthweight infants, tamponade must not be forgotten, since it is now a rapidly
      treatable complication of central venous cannulation.

PMID- 8267804
TI  - Progressive pulmonary stenosis in the fetus: two case reports.
AB  - Fetal echocardiography is a helpful tool in diagnosing and following the natural
      history of fetuses with congenital heart disease. This report describes two
      fetuses with complex congenital heart disease that developed progressive
      pulmonary stenosis in utero. On fetal echocardiogram, one of the fetuses had
      tetralogy of Fallot and the other had a single ventricle. Both fetuses, when
      followed serially by fetal echocardiography, showed pulmonary stenosis that
      progressed in severity. These findings confirm that certain cardiac defects
      progress in severity in utero.

PMID- 8267805
TI  - Monocyte monolayer assay as a predictor of severity of hemolytic disease of the
      fetus and newborn.
AB  - The monocyte monolayer assay (MMA), an in vitro model of in vivo antibody
      mediated red blood cell destruction, was previously reported to predict the
      severity of hemolytic disease of the fetus and newborn accurately when only Rh
      antibodies and antigen-positive babies were studied. We studied 33 women whose
      serum contained antibodies with the potential to cause erythroblastosis fetalis;
      7 of the 33 women had antibodies other than Rh. None of the babies of the ten
      women who had consistently negative test results required intrauterine or
      neonatal transfusions. False-positive MMA results were sometimes found when the
      fetus was antigen negative. Although the predictive value of a negative MMA was
      100%, the efficiency of the MMA was no better than that of the antibody titer.
      Because of the lack of advantage of the MMA as well as the time and expense it
      requires, we cannot recommend the general clinical application of this test at
      this time.

PMID- 8267807
TI  - Association of clinical intra-amniotic infection and meconium.
AB  - The objective of this study was to determine the rate of intra-amniotic infection
      in patients with meconium-stained amniotic fluid compared to controls. With a
      retrospective case-controlled study design, we compared 100 pregnant women with
      meconium to 100 pregnant women without meconium for the development of intra
      amniotic infection. Patients delivered between September 1 and December 31, 1990.
      Exclusion criteria were active infection prior to labor or antibiotic use within
      the 7 days prior to delivery. We diagnosed clinical intra-amniotic infection in
      patients with ruptured membranes by a maternal temperature 100.4 degrees F or
      higher and any two of the following: maternal or fetal tachycardia, uterine
      tenderness, white blood cell count 10,500 mm3 or more, or foul-smelling amniotic
      fluid. Demographic variables, labor characteristics, maternal infectious
      morbidity, and neonatal outcome were analyzed using the Wilcoxin rank test, chi
      square test, or Fisher's exact test as appropriate. The rate of clinical intra
      amniotic infection was significantly higher in women with meconium-stained
      amniotic fluid (8%) compared with women with no meconium (2%) (p = 0.05).

PMID- 8267806
TI  - Magnetic resonance imaging in pregnancies complicated by gestational diabetes
      predicts infant birthweight ratio and neonatal morbidity.
AB  - The use of magnetic resonance imaging (MRI) has been shown to be safe during
      pregnancy and can accurately assess fetal fat and rate of growth. The purpose of
      this study was to investigate with MRI the relationship between maternal weight,
      fat distribution, and glucose levels and neonatal birthweight ratio, percent fat,
      and infant outcome in pregnancies complicated by gestational diabetes. Twenty
      gestational diabetic women were studied at 36 to 38 weeks' gestation with
      hemoglobin A1c, a glucose tolerance test and maternal body fat by electrical
      impedance. MRI scans of the maternal upper arm and from her zyphoid process to
      her pubic symphysis, including all fetal components, were analyzed for percent
      fat of the mother's arm and trunk and her fetus' trunk. All variables were then
      related to infant outcome (birthweight, birthweight ratio, and neonatal
      morbidity). Maternal body composition was related to maternal weight (p = 0.012,
      r = 0.54), as was maternal arm fat (p < 0.005, r = 0.60). Arm fat did correlate
      with trunk fat, but trunk fat did not correlate was well with weight (p = NS).
      Although maternal Hb A1c correlated with maternal weight (p = 0.05, r = 0.43), it
      did not correlate with infant birthweight. In contrast, maternal mean glucose
      levels correlated with both maternal and infant weight and infant birthweight
      ratio (p = 0.05, r = 0.60; p = 0.05, r = 0.42; and p = 0.01, r = 0.64,
      respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267808
TI  - Clavicular fracture of the neonate: can it be predicted before birth?
AB  - A retrospective study of 3873 cephalic vaginal births was undertaken to evaluate
      which factors are associated with clavicular fractures and thereby assess their
      clinical relevance in antepartum prediction. Fifty-two neonates with a fractured
      clavicle were identified, an incidence of 1.3%. Neonates with fractures were
      compared to a control group without fractures. The two groups were matched for
      age, parity, and mode of delivery. The neonates with fractures were found to be
      significantly heavier than controls, with mean birthweights of 3.7 kg and 3.2 kg,
      respectively (p = 0.000). Significantly more newborns in the fracture group
      weighed more than 4 kg (p = 0.02). A similar trend was noted when birthweights of
      previous pregnancies were compared (p = 0.03). Fracture cases had a greater
      incidence of low 1-minute Apgar scores (p = 0.02), and a higher proportion of
      births following abnormal progress of labor (19% of fracture group and 2.9% of
      controls; p = 0.001). Despite these statistically significant differences between
      the groups, it is not possible to predict most cases of fracture before birth,
      since the majority of fractures occur in cases not identified by any of the
      studied parameters.

PMID- 8267809
TI  - Dicavitary uteri with twin gestation: a case following clomiphene citrate therapy
      and review of obstetric outcomes.
AB  - We report the first case of dicavitary twin pregnancy, following clomiphene
      citrate therapy, in a patient with uterus bicornis bicollis and anovulation. A
      review of the literature is presented, and obstetric outcomes and management of
      these rare pregnancies are discussed.

PMID- 8267810
TI  - Spontaneous resolution of hypofibrinogenemia in a triplet gestation associated
      with second trimester in utero death of two fetuses.
AB  - Multiple gestations are increasing in frequency secondary to assisted
      reproductive technologies; therefore, it will become increasingly important to
      know how to manage a multiple pregnancy in which an in utero fetal death has
      occurred. This case report describes the spontaneous resolution of maternal
      hypofibrinogenemia associated with the deaths of two fetuses in a triplet
      gestation. A 29-year-old woman with a triplet gestation had in utero death of two
      monoamniotic fetuses between 15 and 17 weeks' gestation. Maternal plasma
      fibrinogen levels were obtained weekly and were initially in the normal range for
      pregnancy. At 31 weeks' gestation, the fibrinogen level decreased to 239 mg/dl
      and reached a nadir of 150 mg/dl 11 days later. Although the patient received no
      treatment, her fibrinogen level increased to 307 mg/dl over the next 4 days and
      then remained above 260 mg/dl for the rest of her pregnancy. At 35 weeks'
      gestation, a healthy 2090 gm female was delivered. The infant is alive and well
      and developing normally. When there is an in utero death of one fetus of a
      multiple gestation in the second or early third trimester, some authors advocate
      heparinization to reverse maternal coagulopathy; others describe spontaneous
      resolution of hypofibrinogenemia. The role of heparin in treating
      hypofibrinogenemia remains unclear. Hypofibrinogenemia may resolve spontaneously
      without exposing the patient to the potentially serious risks associated with
      heparin therapy.

PMID- 8267811
TI  - Do nifedipine and verapamil potentiate the cardiac toxicity of magnesium sulfate?
AB  - We hypothesized that verapamil and nifedipine would potentiate the cardiac
      toxicity of magnesium in a dose-dependent manner. The hypothesis was tested in
      the isolated perfused rat heart model (Langendorff's apparatus) with Sprague
      Dawley rats. After excision of hearts, each heart was exposed to increasing doses
      of verapamil and nifedipine followed by magnesium sulfate. Heart rate,
      contractility, and left ventricular systolic pressure were measured. Nifedipine
      and verapamil infusion in this model caused dose-dependent decreases in all three
      parameters measured (p values 0.05 to 0.01). The addition of magnesium sulfate
      potentiated these dose-dependent decreases (p values 0.01 to 0.0002). Nifedipine
      and verapamil caused similar depression at equivalent doses. Nifedipine and
      verapamil cause dose-dependent cardiac depression that is potentiated by the
      addition of magnesium sulfate in the isolated perfused rat heart. Caution is
      called for when magnesium sulfate and calcium channel blockers are administered
      in combination.

PMID- 8267812
TI  - Postnatal timing of spontaneous umbilical cord separation.
AB  - A population of 293 consecutive healthy term newborns were enrolled in this study
      to determine the time of their umbilical cord separation while using our current
      nursery protocol with isopropyl alcohol as a method of cord care. Cord separation
      occurred from days 3 to 42, with a mean of 10.9 days. This was considerably
      shorter than previously reported studies in the United States, but still longer
      than reported data from the Netherlands and developing countries. In this study
      there were no significant differences noted when comparing the mode of delivery,
      sex, or race of infant, with respect to time interval for their cord separation.

PMID- 8267813
TI  - Resolution of cystic hygroma, hydrops fetalis, and fetal anemia.
AB  - Cystic hygroma with hydrops fetalis is considered to have grave prognosis. This
      report describes a case of resolution of cystic hygroma, hydrops fetalis, and
      fetal anemia in a female fetus with a normal karyotype. Cystic hygroma and
      hydrops fetalis were noted on a routine ultrasound examination at 27 weeks'
      gestation in a fetus with 46,XX karyotype. Fetal blood sampling at 30 weeks'
      gestation showed fetal hemoglobin of 64 gm/liter. Intrauterine blood transfusion
      at 30 weeks' gestation raised the hemoglobin level to 91 gm/liter. Serial
      ultrasound studies demonstrated complete resolution of cystic hygroma and marked
      reduction of hydrops fetalis. The fetus was delivered at term. She was noted to
      have redundant skin of posterior neck and edema of upper and lower extremities.
      Hemoglobin level at birth was 151 gm/liter. Regular follow-up to 6 months of age
      showed the baby to have normal growth and development, with the return of the
      skin at the posterior neck to normal.

PMID- 8267814
TI  - First trimester bleeding and pregnancy outcome in gravidas with normal and low
      folate levels.
AB  - The purpose of this study was to examine whether women with first trimester
      uterine bleeding and low serum folate have a higher incidence of spontaneous
      abortions and adverse perinatal outcome compared with women whose folate levels
      are normal. Serum folate and vitamin B12 levels were obtained on 225 women who
      presented with first trimester vaginal bleeding; pregnancy outcomes of those
      whose folate or vitamin B12 levels were low were compared with those with normal
      levels using the chi-square test. Of the 151 women included, 52 had low folate
      levels (less than 4.0 ng/ml). Their spontaneous abortion rate and perinatal
      outcomes were similar to those whose folate levels were normal. We concluded that
      in pregnancies complicated by first trimester vaginal bleeding, low folate levels
      do not appear to be associated with an increased risk of pregnancy loss and
      adverse outcome.

PMID- 8267815
TI  - Disseminated herpes zoster in a pregnant woman positive for human
      immunodeficiency virus.
AB  - We report a case of disseminated herpes zoster in a pregnant patient positive for
      the human immunodeficiency virus (HIV). Disseminated zoster was the first
      manifestation of HIV infection in this patient. In HIV-positive patients, zoster
      may be complicated by cutaneous dissemination, visceral involvement, and death.
      Intravenous acyclovir may prevent serious sequelae in both mother and fetus.

PMID- 8267816
TI  - Response of neonates to vibroacoustic stimulation.
AB  - The response to vibroacoustic stimulation was evaluated in 30 healthy full-term
      newborns and in five newborns with severe neurologic deficits. The stimulus was
      applied during a period of quite sleep and a subsequent period of quiet sleep
      served as the control. All 30 healthy newborns reacted by changing from a state
      of quite sleep to an active sleep state as determined by heart rate acceleration,
      irregular respiration, and the appearance of limb movements. Heart rate increased
      by 19.5 +/- 9.7 beats/min (mean +/- SD) for a mean duration of 21.4 +/- 11.9
      seconds. The five newborns with severe neurologic deficits did not show any
      response to vibroacoustic stimulation, and auditory brainstem evoked responses
      were also absent. We conclude that this technique may be useful as a screening
      procedure in the evaluation of the neurologic integrity of newborn infants.

PMID- 8267817
TI  - Placenta percreta with bladder invasion: report of three cases.
AB  - Three cases are reported of placenta percreta with urinary bladder wall invasion.
      All three patients had complete placenta previa and each had five previous
      cesarean sections. Placental invasion caused a giant vesicouterine fistula in the
      first case. The second patient had a cesarean hysterectomy and the placental
      portion that penetrated the bladder wall was left to absorb spontaneously. The
      third patient underwent a cesarean supracervical hysterectomy during which the
      bladder invasion was left undisturbed. She received intraoperative methotrexate,
      and pelvic packing and bilateral hypogastric ligation were helpful in hemorrhage
      control.

PMID- 8267818
TI  - Information-processing mediating the location-distance interference in motor
      short-term memory.
AB  - We reviewed the literature on basic psychological correlates of the well-known
      phenomenon of the location-distance interference in motor short-term memory
      (Kerr, 1978; Walsh, Russell, Imanaka, & James, 1979). The location-distance
      interference in motor short-term memory has frequently been demonstrated as an
      unavoidable interference phenomenon observed in the reproduction of movement
      location and distance in arm positioning. The most important aspect of this
      phenomenon is that even when a subject concentrates on a specific cue (i.e.,
      either end-location or distance) the other cue is also coded unintentionally and,
      as a result, the reproduction movement guided on the basis of the specific cue is
      unavoidably influenced by the other nonspecific cue. In this review article, we
      first reviewed the literature on the basic theories and nature of short-term
      memory, particularly on the limited processing capacity. We then referred to the
      unlimited, automatic processing in visual-verbal domains, referring to the Stroop
      phenomenon. Finally, in conjunction with the notion of automatic processing, we
      examined the possible aspects of information processing which may be responsible
      for mediating the location-distance interference in motor short-term memory.

PMID- 8267819
TI  - Changes in relations between surface electromyogram and fatigue level by
      repeating fatiguing static contractions.
AB  - Changes in relations between surface electromyogram (EMG) and fatigue level
      estimated by fatigue sensation were studied during repeated fatiguing static
      contractions. Six male subjects performed elbow flexion of 13-15%MVC.
      Contractions were repeated 5 times (C1, C2, C3, C4, C5) with 5 min intervals of
      rests. The contractions continued until the onset of fatigue sensation such as
      obvious pain or considerable tiredness. Bipolar surface EMGs were recorded from 6
      synergists of elbow flexors. Mean amplitude (AEMG) and relative power spectrum
      (RPW) of EMG were calculated. Partial correlation coefficients between time,
      AEMG, and RPW during each contraction were calculated. AEMG increased with time.
      EMG spectrum shifted towards lower frequencies with time. The correlations
      between AEMG and RPW were negative below 60Hz. AEMG and RPW were compared between
      C1 and C2-C5 being related with fatigue sensations. The changes in AEMG and EMG
      spectrum with the repeated contractions were similar to those with the
      development of fatigue. The increases in AEMG with the repeats were seen in most
      synergists in 4 subjects. Though EMG roughly reflected the fatigue during work,
      the changes of EMG were thought to include active adaptation to work.

PMID- 8267820
TI  - [The relationships of sex hormone binding globulin (SHBG) with high density
      lipoprotein cholesterol and fasting insulin in healthy men].
AB  - The relationships of sex hormone binding globulin (SHBG) with high density
      lipoprotein cholesterol (HDL-C) and fasting insulin (IRI) were investigated in
      healthy employed men (n = 235). In simple correlation analysis, the SHBG was
      positively related to total cholesterol and HDL-C, and negatively related to IRI.
      There were no relationships among SHBG, triglyceride and fasting blood glucose.
      In multiple linear regression analysis, SHBG was one of determinant of HDL-C, but
      not IRI. From these results, it was suggested that SHBG was one of the
      determinants of HDL-C level in healthy men.

PMID- 8267821
TI  - [Cleaning and disinfection of endoscopes in general practice and ambulatory
      care].
AB  - The legal conditions in Germany for cleaning and disinfection of endoscopes
      depend on the terms of reference of the "Bundesgesundheitsamt (BGA)" and the
      "Deutsche Gesellschaft fur Hygiene und Mikrobiologie (DGHM)" and the
      "Unfallverhutungsvorschrift (UVV) der Berufsgenossenschaft fur Gesundheitsdienst
      und Wohlfahrtspflege". The different regulations and the resulting practical
      consequences for manual and mechanical cleaning and disinfection of rigid and
      flexible endoscopes are described. Particularly the HBV-HIV-problems as well as
      the respective inactivation times resulting there from, standby times and
      concentrations of different solutions for disinfection are discussed.
      Presentation of the practicability of the different steps in daily ENT-practice
      and ambulance.

PMID- 8267822
TI  - [In vitro studies of possible transmission of human immunodeficiency virus (HIV)
      by allogeneic cartilage transplants].
AB  - With the increasing prevalence of the human immunodeficiency virus (HIV), the
      possibility of a transmission of HIV via allogenic transplants has increased. To
      assess the risk of transferring HIV with allogenic cartilage grafts we
      investigated the susceptibility of chondrocytes to the virus. Our results
      indicate the absence of the HIV receptor (CD-4-molecule) on chondrocytes by
      immunohistochemistry and FACS analyses. Furthermore cultures from chondrocytes
      and high doses of HIV-1 did not show an active replication. Hence, we conclude
      that normal cartilage cells cannot be infected by HIV. This means that the risk
      of HIV transmission by cartilage allografts is very low if no contaminating
      tissues like blood, perichondrium and calcifications etc. are present.

PMID- 8267823
TI  - [HIV-associated Kaposi sarcoma in the head and neck area: a clinical, morphologic
      and therapeutic review].
AB  - Since 1987 233 HIV-infected patients have been treated at the Department of
      Otorhinolaryngology, Head and Neck Surgery of the Ludwig-Maximilians-University
      of Munich. 70% of these patients had advanced immunodeficiency disease (ARC and
      AIDS). 46 presented a Kaposi's sarcoma (KS) in the head and neck region. 91% were
      homosexual men. KS was most often located in the mouth (67%), oropharynx (65%)
      and skin (39.1%), while the larynx (10.9%), hypopharynx (8.7%), lymph nodes
      (6.5%) and nasopharynx (4.3%) were rarely involved. In 15 patients, a KS of the
      head and neck region was the initial symptom for the HIV-infection. Although the
      clinical features of this disease are typical, histological examination is
      required because differential diagnosis can show other rare diseases, such as
      bacillary angiomatosis, which are easily cured. The morphology of early plain or
      elevated KS exhibits more irregular vascular components while the nodular KS is
      dominated by sarcomatous cell lines. Immunohistochemical studies with antibodies
      to viral components revealed no reactivity to HIV-, HPV-, HSV-, EBV- and CMV
      antigens. The best local treatment proved to be CO2- or ND:YAG-laser therapy.
      Cutaneous lesions were treated with camouflage or by fractionated radiotherapy.
      Advanced disease showed best response to systemic chemotherapy. Despite the
      advanced stage of immunodeficiency syndrome, an adequate local or systemic
      therapy can obviously improve the quality of life in HIV-infected patients.

PMID- 8267824
TI  - [Treatment of laryngotracheal papillomatosis with combined use of laser surgery
      and intralesional administration of alpha-interferon (Roferon)].
AB  - Since the discovery of a viral aetiology (HPV 6 and 11), alpha-interferon (alpha
      IFN) following surgical procedures has proved effective. In this article, we
      report on nine patients (four children, five adults) with laryngotracheal
      papillomatosis who received interstitial alpha-2a-IFN injections (Roferon, 3 Mio.
      IU) into the laser surgical coagulation area following laser excision of
      papilloma. The average duration of treatment is 29 months (Table 3). In all cases
      IFN therapy proved to respond with no initial failure. In five cases the
      treatment was finished after a four-year period with no signs of tumour
      recurrence (Table 4). One patient (N., P. in Table 4) with excessive
      manifestations spread over pharynx, larynx and trachea achieved partial remission
      with definite control over the disease for (so far) 17 months. Two patients have
      remained free of disease for five and seven months (J., D. in Table 4 and Fig. 1
      a-c) after initial therapy onset with complete remission. Another child (W., F.
      in Table 4) had a recurrence after complete remission for ten months and no
      observation period for eight months. After recurrent IFN-application this patient
      has been tumour-free for now six months. Apart from flu-like symptoms no side
      effects of intralesional IFN-injections could be seen. The obtained results
      confirm that combined laser surgery and alpha-IFN treatment is the therapy of
      choice up to now. Since IFN is not a benign agent and systemic administration
      bears potential side effects, adjuvant intralesional alpha-IFN is effective and
      safe and extends the therapeutical possibilities available in laryngotracheal
      papillomatosis.

PMID- 8267825
TI  - [Annual meeting of the German Society of Otorhinolaryngology, Head- And Neck
      Surgery].

PMID- 8267826
TI  - [Relation between tone and speech perception in noise-induced hearing loss-
      determination of characteristics].
AB  - The relation between tone and speech hearing in noise-induced hearing loss is
      argued controversely. Important publications according to which close
      correlations between both audiological methods are extensively supposed, are
      listed initially. Own research results that have already been published otherwise
      are introduced briefly. After that--with the help of discrimination functions on
      the monosyllable level--a correct order of the audibility is possible with a high
      hit share. The incorrect empirical adaptation of the hearing loss tables can be
      improved upon by quadratic optimation. Simultaneously, the polynomic functions
      calculated with the help of the quadratic optimation show frequency-specific
      characteristics. After addition of these functions one gets a virtual
      characteristic--tone and speech hearing--with a general character for noise
      induced hearing loss. We believe that we have found by this mathematical method a
      new way for the solution of this difficult complex of questions. Our opinion is
      that the procedure mentioned above is also suitable for other types of hearing
      disturbances and for other languages.

PMID- 8267827
TI  - [Ear manifestations in adolescents after closure of lip-jaw-palate- or isolated
      palatal clefts].
AB  - We examined two groups of teenagers who had been surgically treated as small
      children for cleft palate. Most patients were between 13 and 21 years of age. One
      group had been looked after by the Dept. of Orthodontics at the University of
      Erlangen-Nurnberg, the other by the Dept. of Orthodontics at the University of
      Rostock. There were differences in sequence and time of the surgical closure
      between the two departments. Additionally, 60% of the people treated in Rostock
      had a velopharyngoplastic, which was rarely the case in Erlangen. In both groups
      only a few patients had been seen by an ENT-doctor regularly. Only some patients
      had been previously treated with tubes. There was one patient in each group with
      a bilateral, most likely genetically determined, sensorineural hearing loss. In
      Erlangen we examined 66 teenagers (132 ears). Six ears had been previously
      treated with one or more tympanoplasties. 10 ears needed further treatment due to
      a seromucotympanon, adhesions, perforations of the ear drum, suspicion of
      cholesteatoma or insufficient improvement of hearing after previous
      tympanoplasty. Another 18 ears showed signs of former inflammations. The control
      group in Rostock included 63 patients (i.e. 126 ears). 14 of the ears examined
      had undergone one or more tympanoplasties previously. 13 other ears needed
      further treatment for seromucotympanon, adhesions, perforations of the ear drum,
      insufficient improvement of hearing after tympanoplasty or cholesteatoma.
      Residuals due to prior inflammations were found in another 26 ears. Possible
      reasons for the different occurrence of middle ear problems in both groups are
      discussed.

PMID- 8267828
TI  - [Incidence of Doppler ultrasound detectable stenoses of cervical arteries in
      patients with cochlear-vestibular symptoms].
AB  - Doppler ultrasound examination is an easy and non-invasive examination technique
      to image the anatomical and functional situation of cervical vessels. An
      increasing number of ENT-specialists has been using Doppler sonography in the
      diagnosis of cochlear and vestibular disorders. We analysed the frequency of
      pathological Doppler examination results of 150 patients with vertigo, hearing
      loss and tinnitus. Especially patients with vertigo bear a greater risk for
      stenosis of the extracranial arteries (28%) compared to an asymptomatical
      population (1%). Patients with hearing loss and tinnitus showed a different
      degree of artery disorders (23% of the patients with hearing loss; 18% of the
      patients with tinnitus). Patients bearing no risk for atherosclerosis showed in
      13% (vertigo) and 8% (hearing loss and tinnitus) stenosis of the cervical
      arteries. Thus we found by Doppler ultrasound examination more stenoses in
      patients with cochlear or vestibular symptoms than in an asymptomatical
      population. The early attribution of stenosis to a malfunction of the inner ear
      helps to avoid invasive examinations of cervical vessels. In addition to this,
      imminent cerebral ischaemia can be revealed at an early stage.

PMID- 8267829
TI  - [Reliability of diagnostic procedures in facial paralysis with special reference
      to magnetic resonance tomography].
AB  - Facial nerve palsy is commonly examined using a variety of topodiagnostic and
      electrophysiological tests. More recently, MRI has also been used to study
      lesions of the facial nerve. Due to varying time intervals between the onset of
      symptoms and clinical examination, however, the diagnostic value of these
      procedures remains limited. In the present study, 30 patients with facial nerve
      palsy of diverse origin were examined with MRI (1.5 Tesla magnetom) using a
      special surface coil and 30 degrees parasagittal slices of 3 mm thickness. These
      special modifications enabled us to visualize the nerve in its entire course
      through the temporal bone. After the application of Gd-DTPA the enhancement of
      the contrast medium could be verified in all cases. A moderate enhancement in the
      geniculate ganglion as well as in the labyrinthine segment correlated with a good
      prognosis in terms of complete restoration of facial nerve activity, while an
      increased enhancement correlated with a poor prognosis. Our results indicate that
      MRI is of superior diagnostic value as compared to clinical and electrodiagnostic
      tests, at least in the patients we examined in this study. Still, further
      evaluations are necessary to justify a possible routine clinical use of this
      procedure.

PMID- 8267830
TI  - [Mechanisms of cognitive performance deficits in cerebrovascular diseases].

PMID- 8267831
TI  - [Replacement of defects in the ear ossicular chain by wire prostheses].

PMID- 8267832
TI  - [Legal aspects of modern transplantation surgery].
AB  - The legal and legislative aspects of transplant surgery in reunified Germany have
      been the subject of intense and even fierce discussions both recently and at the
      present time. Legally, the situation in Germany is not governed by specific laws
      and the reunification of Germany has posed new problems since the codification of
      transplantation that had been practised in the former German Democratic Republic
      is still valid in what are now the new Federal Laender. As a result, uniform
      legislation is more imperative than ever for the benefit of all the involved
      physicians, hospitals and patients. Independent of the models that have been
      proposed in the past for solving this legal tangle it has been overlooked that
      the so-called "extended consent" solution would not only fully take into account
      the self-determination of the individual but would also appeal to the civic
      responsibility of the citizen, i.e. his social duties within the community.
      Hence, the new German legislative body must face the challenge to have the
      courage to arrive at a clear and positively legal assessment of values and a
      uniform regulation governing this highly sensitive complex to do justice to the
      needs of modern transplant medicine. While doing so, whatever has been laid down
      in the Constitution must not suffer should there be any collision with
      fundamental rights; maximum agreement with these must therefore be aimed at.

PMID- 8267833
TI  - [Effect of ozone on airborne microorganisms].
AB  - The microbicidal effect of ozone in air was tested at concentrations between 50
      and 600 micrograms/m3 against the species: Staphylococcus epidermidis,
      Micrococcus luteus, Arthrobacter citreus, Bacillus subtilis (veg.), Escherichia
      coli, Salmonella typhimurium, Serratia marcescens, Pseudomonas fluorescens and
      Candida albicans. The microorganisms were exposed on membrane filters at 60-75%
      relative humidity and 21.5-22.5 degrees C. After exposure times between 1 min and
      60 min, the filters were incubated on appropriate agar media. The effect of ozone
      was determined by comparing the number of colonies on exposed filters to the
      number on nonexposed filters. The die-off curves (colony count against time)
      proved not to be rectilinear, but to become steeper with increasing time of
      exposure. Furthermore, the velocity of reduction increased more than proportional
      with increasing concentration of ozone. Therefore, the bacterial decay seems not
      to follow first order reaction kinetics. The values presented for k (constant of
      the velocity of die-off) and D (decimal reduction time) are valid only for narrow
      ranges of the initial part of the exposure. Concentrations of 50 to 100
      micrograms (0)3/m3 for 1 h resulted only in little reduction, whereas 500 to 600
      micrograms/m3 for one hour led to 99% reduction in all bacterial species tested.
      The gram-positive species seemed to be more sensitive than the gram-negative
      species, C. albicans proved to be more resistant than the bacteria.

PMID- 8267834
TI  - Virucidal activity of an activated sludge supernatant.
AB  - The virucidal activity of the activated sludge aqueous phase was studied from the
      time of initial inoculation with a poliovirus type 1 suspension and for durations
      of three and nine days. The mixtures were incubated in presence of a nutritive
      medium at 26 degrees C and samples were drawn at regular intervals of time for
      viral titration. The activated sludge supernatant (ASS) caused an important
      decrease of the titer of the poliovirus type 1 suspension especially after nine
      days of incubation. There was an average reduction of the viral titer of 79%
      after three days and 97% after nine days. When incubating the ASS with a
      nutritive medium before inoculating it, the viral decrease was much greater than
      when incubating without nutritive medium. When sterilizing the ASS before
      incubation and then inoculating it, no significant virucidal activity was
      observed (0% to 6%). Furthermore, when the ASS was subjected to a sterilization
      by filtration after incubation and was then inoculated, there existed a lower but
      not negligible viral inactivation (53% to 64%). The virucidal activity
      potentiality of the ASS is therefore due to microorganisms acting both directly
      as a support for viral particles adsorption and indirectly via the synthesis of
      substances with virucidal activity. When freezing and thawing the incubated ASS,
      and then sterilizing it by filtration before inoculation, the viral decrease
      reached 87% to 94%. This proves that the virucidal substances are only partly
      excreted by the microorganisms.

PMID- 8267835
TI  - [Inactivation of bacteria and coliphages in surface water highly polluted by
      secondary effluent and purified by flocculation and filtration by means of UV
      irradiation at a pilot plant scale].
AB  - The water of a channel in Berlin which is highly polluted by municipal sewage
      effluent is treated at the phosphate elimination plant (PEP) Tegel by
      flocculation and filtration in order to reduce eutrophication in the following
      Lake Tegel. The elimination of bacteria and coliphages in the effluent of the PEP
      was investigated in a scale pilot UV irradiation reactor installed at the outlet
      of the PEP Tegel. The influence of technical parameters such as flow rate and the
      arrangement of 23 UV lamps in the reactor on the inactivation was tested. The UV
      irradiation dose was calculated 119 mJ/cm2 and 49 mJ/cm2 at a flow rate of 50
      m3/h and 120 m3/h, respectively and for an irradiation zone of 97.5 cm. The
      colony count of bacteria and concentrations of coliform organisms, E. coli, and
      feacal streptococci as well as the plaque forming units of coliphages in the
      influent of the UV reactor were reduced 2-3 lg units by an irradiation dose of
      119 mJ/cm2. These elimination was found being only one lg unit at a UV
      irradiation dose of 49 mJ/cm2. The concentration of E. faecalis and Coliphages f2
      seeded into the influent of the UV reactor decreased after UV irradiation by 119
      mJ/cm2 by 2-4 lg units and 1-2 power of magnitude, respectively. A UV dose of 49
      mJ/cm2 caused only a 90% elimination of E. faecalis and a 75% inactivation of
      Coliphages f2. Due to heterogenous distribution and the different retention
      period of the inflowing water in the irradiation zone, the inactivation of E.
      faecalis and Coliphages f2 was unequal. Both test organisms decreased in the
      middle of the reactor up to 2 lg units more than at the sides of the reactor. The
      hygienic-microbiological quality of a secondary effluent from sewage treatment
      plants can be improved by a combination of flocculation-filtration and UV
      irradiation due to their additive elimination effect. However, this UV reactor,
      which was tested under field conditions can only ensure the inactivation of
      bacteria and coliphages in the pretreated effluent, if more homogenous
      distribution of the inflowing water can be achieved. Further, the water must be
      irradiated by a higher UV dose.

PMID- 8267836
TI  - [Connection between air quality and room climate and estimation of dwellings by
      health-impaired inhabitants].
AB  - The investigation was performed in winter 1990 and 1991 when measurements were
      taken in 16 dwellings of patients, recruited from a pulmologic outpatient centre.
      Patients suffered from repeated respiratory irritations which they attributed to
      dwelling conditions. Inhabitants reported by means of questionnaires and
      standardized scales the dwelling situation and their dwelling behaviour,
      subjective ratings of indoor environmental quality as well as ratings of
      wellbeing. The load of indoor pollutants (CO2, CO, NO2, HCHO), biological agents
      (fungal spores, house dust mites) as well as indoor climate factors were
      assessed. The measurements revealed an evident load at least in one parameter; in
      the majority of dwellings combined loads of air pollutants and biological agents
      were apparent. Homes supplied with gas as main energy source had significantly
      higher concentrations of CO2, CO and NO2. At noon, exposure limits of CO2 and NO2
      were frequently exceeded. Inhabitants of homes being supplied with electricity
      instead of gas gave significantly better air quality ratings. The correlations
      between the average score concerning the rated health quality of their homes and
      the rate of excess of exposure limits are significant: The health quality ratings
      are significantly related to the concentrations of "air quality indicators",
      which induce the feeling of stale air (CO2) and mucosa irritations (NO2). Ratings
      of wellbeing are significantly connected to objective parameters, i.e. NO2
      baseline load, fungal spores in the air and the difference between wall-air
      temperature. Our study suggests that people suspecting a connection between their
      health impairment and dwelling conditions should be taken serious. The
      measurement program proved to be a suitable screening procedure to assess adverse
      environmental influences in homes. More homes should be investigated to further
      support our findings.

PMID- 8267837
TI  - [Cohort study on respiratory diseases and lung function in schoolchildren in
      southwest Germany. I. study design, prevalence and incidence of respiratory
      diseases].
AB  - A prospective cohort study on schoolchildren was conducted during the years 1977,
      1979 and 1985 in Mannheim and the Black Forest county near Freiburg to
      investigate the regional differences in respiratory diseases and symptoms. Each
      survey included a lung function test and questions on respiratory symptoms. The
      response rates were high (84% averaged over the years and areas). A total of 8514
      children participated in the study, 2066 children took part in two and 1486 in
      all three surveys. Prevalence and incidence rates of 11 respiratory and allergic
      diseases are reported in part 1 of the publication. In further parts, prevalence
      will be analysed using regression techniques and a comparison in the development
      of lung function between the different regions will follow. In general,
      prevalences of the respiratory and allergic diseases were higher for boys than
      girls at age 8-10. In contrast, 16 year old girls were equally affected and
      sometimes showed higher prevalences than boys except for asthma. 1977 and 1979
      higher prevalences of respiratory symptoms were found in Mannheim compared to
      Freiburg. Allergic symptoms occurred more frequently in the area around Freiburg.
      No difference in prevalence and incidence could be demonstrated for the year 1985
      between the two regions.

PMID- 8267838
TI  - [Clonal spreading of a multidrug resistance Citrobacter freundii strain at a
      neonatal intensive care unit].
AB  - This paper reports on the epidemic spreading of a multiresistant Citrobacter (C.)
      freundii strain at a neonatal intensive care unit. A premature baby of the 27th
      week of pregnancy died from septic shock caused by this strain. According to the
      result of a statistical analysis of risk factors a connection between the
      colonization of neonates and the feeding with an enteral feeding tube was
      probably. This suspicion could be confirmed by the detection of the
      multiresistant strain in the infant formula. Plasmid analysis, examination of
      outer membrane proteins and lipopolysaccharides of these C. freundii strains
      demonstrated the identity of all isolates. The resistance to antibiotics of this
      multiresistant C. freundii clone was determined by a plasmid belonging to
      incompatibility group C with a molecular weight of 110 MDa. This plasmid was
      involved also in other nosocomial outbreaks. It persisted more than 7 years in
      the hospital flora of the intensive care unit.

PMID- 8267839
TI  - Microbiological quality of artisanal ice cream.
AB  - In the course of the years 1990 and 1991, 396 samples of artisanal ice-cream had
      been collected from different ice-cream shops in Udine and province and analysed.
      All tested flavours contained aerobic germs, coliforms, Enterococci and yeasts in
      different quantities. In the analysed samples neither Salmonellae spp., nor
      Listeria monocytogenes nor Staphylococcus aureus were detected. Numerous species
      of coliforms and yeasts were randomly isolated and identified. The statistical
      analysis, used to compare the variables (flavour, month, year), showed
      significant differences among the samples analysed in the two years. In
      September, the means of the total aerobic count were significantly different from
      the ones of July and of August. No significant differences were noted in the
      means of coliforms, total aerobic counts and yeasts in the different flavours.
      The techniques for recovery of freeze-stressed coliforms in artificially
      contaminated samples of ice-cream showed that the three techniques, which use
      both selective and non-selective mediums, are better than those ones, which use
      only selective mediums. Lastly, with regard at the coliform values, the ice
      creams tested have small-medium quality. In fact 26% of the ice-creams cannot be
      sealed, according to the Italian Ministry Ordinance (October 11, 1978).

PMID- 8267840
TI  - [Demonstration of nosocomial pathogens in the nasal swabs of medical students].
AB  - A single examination of nasal swabs of 183 medical students revealed 87 persons
      (47.5%) being carrier of nosocomial pathogens. Enterobacteriaceae could be
      isolated in 35 cases (19.1%), Staphylococcus aureus in 62 cases (33.9%). Two
      different species of nosocomial pathogens were found simultaneously in 10
      persons, most frequently comprising Staphylococcus aureus and Enterobacteriaceae.
      After the first isolation of Enterobacteriaceae control studies of 20 persons
      done after a 3-week-period could state the primary isolation in 11 cases (55%).
      The findings indicate the importance of the nose as a reservoir for nosocomial-
      even gram-negative--pathogens.

PMID- 8267841
TI  - [Epidemiology of urticaria in infants].
AB  - Epidemiology of childhood urticaria and especially that of infants is badly
      understood because of a lack of studies devoted to this age group. A
      retrospective study of 40 infants that were hospitalised for urticaria has been
      made to clarify the factors that produce urticaria at that age. Certain clinical
      signs seem to be more frequent at this age, such as the bruised appearance of the
      lesions. Acute urticaria is the most frequent form. An etiology has been
      confirmed or suspected in 2/3 cases: intolerance of cow milk proteins before 6
      months, drug and infection causes after 6 months. Prospective studies of
      infantile urticaria are necessary.

PMID- 8267842
TI  - [Classification of urticaria and genetic angioedema].
AB  - Urticaria and genetic angioedema may be divided into three groups, according to
      their pathogenesis: anomaly of the complement system, physical origin or
      metabolic origin. Recent developments essentially concern hereditary angio
      oedema, with location of the gene of the inhibitor of C1 esterase on chromosome
      11 and the discovery of deletions or mutations of this gene in affected families.

PMID- 8267843
TI  - [Physical urticaria and angioedema in children].
AB  - Urticaria and physical angioedema frequency is hard to evaluate in children. In
      this series, we keep 53/1000. Physical urticaria is found in 36% of the cases and
      concerns cholinergic urticaria, urticaria to cold, idiopathic dermographism and
      mastocytosis, and delayed urticaria to pressure. The authors insist on the
      interest of the etiologic research in these forms of infantile urticaria.

PMID- 8267844
TI  - [Food urticaria in children. Review of 51 cases].
AB  - Food origin seems to have a special place in the etiology of infantile urticaria,
      as it forms 62% of a series of 51 observations of urticaria in children, greater
      than drug etiology (22%), physical urticaria (8%) and contact urticaria (8%).
      Distinction between true and false food allergy, which is important for prognosis
      and evolution, puts true food allergy (55%) in the lead before false (7%). A
      reason for this, the atopic concept, was seen in 67% of the food urticarias,
      corresponding apparently to true food allergy. If in the majority of these cases
      the pathway of sensitizations was unknown, in very rare observations the
      sensitization pathway was reported as an inhalation or even a sensitization in
      utero. Finally, infantile urticaria, more serious because of the vital risks that
      may be associated with it, deserves a special comment from the etiological
      viewpoint: observation of urticaria (and shock) to peach in an infant of 4
      months, to wheat flour at 5 months and egg at 6 months are a demonstration that
      between 4 and 6 months intolerance of cows milk proteins is not the only etiology
      of infantile urticaria. For prognosis, early detection of true food allergy in
      children gives hope of better results than in adults, with higher chances of
      regression of the sensitization.

PMID- 8267845
TI  - [Urticaria, angioedema and complement abnormalities].
AB  - For urticaria and/or angio-oedema in a child, it may be valuable to measure some
      complement components, especially C3 and C4. If a state of hypocomplementemia is
      found, an attempt must be made to understand its significance. Is it consumption
      exaggerated by immune complexes in some urticarias of infectious or drug origin
      or urticarial vascularitis, or more exceptionally a congenital deficiency of some
      factors?

PMID- 8267847
TI  - [Urticaria and angioedema caused by mastocytosis].
AB  - Mastocytosis in children are very polymorphic, most often remaining isolated,
      without an associated visceral lesion. Beside the phenomenon of "urtication"
      characteristic, papulo-nodular lesions of urticaria and angio-oedema during the
      mastocytosis are rarely met. In contrast, congestive signs with pruritus,
      dermographism, congestive erythema and general signs are frequent.

PMID- 8267846
TI  - [Urticaria and angioedema associated with cryoglobulinemia in children].
AB  - Urticaria and/or angio-oedema due to cryoglobulins or cold agglutinins are
      exceptional in children. However, some observations have been reported in the
      literature during viral infections (infectious mononucleosis, hepatitis B) and
      vascularities.

PMID- 8267848
TI  - [The adverse effects of the preparations of the active principles of Chinese
      herbal drugs].

PMID- 8267849
TI  - [Pharmacognostical studies on medicinal plant Caryopteris in Qiang nationality
      district].

PMID- 8267851
TI  - [Influence of the blight of Morinda officinalis How on microscopic structure and
      constituents of the host].
AB  - The results showed that microscopic structure in biennial roots, the contents of
      B and Mn in nutritive organ and beta-sitosterol content in roots, stems of
      Morinda officinalis were affected markedly. The total sugar content in the roots
      and aerial stems was decreased by 5.42%-15.29%.

PMID- 8267850
TI  - [Determination of essential oil in fruits of Cnidium by computer image analysis
      system].

PMID- 8267852
TI  - [Collection, evaluation and utilization of local varieties of Fritillaria
      thunbergii Miq].
AB  - Nine local varieties of Fritillaria thunbergii were collected and their plant
      morphology, phenology, disease resistance yield characters and breeding rate were
      studied. A new and better variety (Duozhi) was found and put to use.

PMID- 8267853
TI  - [The effect of stimulation and toxicity of rhizoma Pinelliae processed by ginger
      juice on animals].
AB  - Rhizoma Pinelliae boiled with ginger juice has less stimulation and toxicity on
      animals, which is similar to Rhizoma Pinelliae processed by alum solution. The
      effect of Rhizoma Pinelliae that has been immersed in ginger juice is not as good
      as that of the ginger-boiled. It was also observed that the stimulation of raw
      Rhizoma Pinelliae on mice could be reduced when the mice was given fresh or
      boiled ginger juice. The Rhizoma Pinelliae processed by ginger juice and alum has
      very little toxicity on mice.

PMID- 8267854
TI  - [Processing of medicinal peony].

PMID- 8267855
TI  - [Application of beta-cyclodextrin inclusion complex in liushen pills].
AB  - 01 Liushen Pills (prepared by beta-CD inclusion complex) and 02 Liushen Pills
      (prepared according to the normal way) were compared by quality inspection,
      stability test, pharmacological experiments of irritative effects and dissolution
      test. The results indicated that 01 Liushen Pills were superior to 02 Liushen
      Pills.

PMID- 8267856
TI  - [Chemical constituents of Cistanche deserticola Y.C.Ma].
AB  - Seven compounds have been isolated from Cistanche deserticola. On the basis of
      spectral data (NMR, IR, MS, UV) they were identified as beta-sitosterol,
      daucosterol, succinic acid, triacontanol, acteoside, betaine and polysaccharose.

PMID- 8267857
TI  - [Chemical constituents of Rosa laevigata Michx].
AB  - Six compounds were isolated from Rosa laevigata. Five of them were obtained from
      the ethanolic extract and identified as 2 alpha, 3 beta, 19 alpha, 23
      tetrahydroxyurs-12-en-28-oic acid, 2 alpha, 3 alpha, 19 alpha, 23-tetrahydroxyurs
      12-en-28-oic acid, euscaphic acid, beta-sitosterol and daucosterol. The other one
      was obtained from the acetate of emulsive layer of the petroleum ether and
      elucidared as 2 alpha, 3 beta-dihydrolup-28-methyl ester diacetate.

PMID- 8267858
TI  - [Chemical constituents of Acanthopanax senticosus (Rupt. et Maxim.) Harms].

PMID- 8267859
TI  - [Effect of Gardenia jasminoides Ellis (GJE) on the blood flow of internal organs
      at the early stage of acute necrotizing hemorrhagic pancreatitis in rats].
AB  - Effect of GJE on the prevention and treatment of experimental acute pancreatitis
      was observed by means of testing pancreatic, hepatic, gastric and intestinal
      blood flow. The results show that the blood flow of internal organs that
      decreases significantly at the early stage of acute necrotizing hemorrhagic
      pancreatitis in rats can be picked up by GJE especially pancreatic.

PMID- 8267860
TI  - [Effect of naomaitong on basilar artery rings and portal vein strips].
AB  - Both Naomaitong and single salvia miltiorrhiza inhibit the contraction of rabbit
      basilar artery rings evoked by CaCl2 and KC1 and have nonspecific antagonism
      against the quantity effect curve of CaCl2. Naomaitong and single salvia
      miltiorrhiza also inhibit the contraction of rabbit basilar artery rings evoked
      by KC1. Clearly the inhibitory function of the former is greater than that of the
      latter. But on the myogenic activity of portal vein strips in rats Naomaitong has
      light inhibitive effect while salvia miltiorrhiza has not.

PMID- 8267861
TI  - [Comparative study on the anti-free-radical damage by vital energy-reinforcing
      method and blood-tonifying method].
AB  - A comparative study has been conducted on the anti-free-radical damage by the
      vital energy-reinforcing and blood-tonifying methods. The results shows that
      Sijunzi decoction and Siwu decoction can increase the vitality of SOD, accelerate
      the elimination of free-radical and inhibit the growth of LPO and MAO-B. This
      means that both these two methods help to delay senility and the vital energy
      reinforcing one is more effective.

PMID- 8267862
TI  - Tempeh: a mold-modified indigenous fermented food made from soybeans and/or
      cereal grains.
AB  - A variety of indigenous fermented foods exist today; however, tempeh has been one
      of the most widely accepted and researched mold-modified fermented products.
      Tempeh is a traditional fermented food made from soaked and cooked soybeans
      inoculated with a mold, usually of the genus Rhizopus. After fermentation has
      occurred, the soybeans are bound together into a compact cake by dense cottony
      mycelium. An important function of the mold in the fermentation process is the
      synthesis of enzymes, which hydrolyze soybean constituents and contribute to the
      development of a desirable texture, flavor, and aroma of the product. Enzymatic
      hydrolysis also may decrease or eliminate antinutritional constituents;
      consequently, the nutritional quality of the fermented product may be improved.
      Current technology and new scientific advancements have enabled researchers to
      examine specific strains of Rhizopus and new substrates such as cereal grains.
      Because Kansas produces numerous cereal grains, production of a fermented tempeh
      like product using wheat, sorghum (milo), oats, rye, barley, corn, and triticale
      is a definite possibility for generating a Kansas Value-Added Product. In this
      study, several different tempeh-like products were produced using various cereal
      grains inoculated with Rhizopus oligosporus NRRL 2549 or R. oligosporus NRRL
      2710. Grains used included hard red winter wheat, triticale, yellow sorghum
      (milo), and red sorghum (milo). The grain source as well as the strain of R.
      oligosporus used influenced the product's appearance, flavor, and patty
      integrity. Results showed that R. oligosporus NRRL 2549 produced more mycelium at
      a more rapid rate than did the R. oligosporus NRRL 2710 strain. The combination
      of red sorghum and R. oligosporus NRRL 2549 yielded a product with good patty
      texture, aroma, and appearance. Furthermore, the red sorghum fermented product
      was well suited for slicing. On the other hand, yellow sorghum inoculated with
      either R. oligosporus NRRL 2549 or R. oligosporus NRRL 2710 failed to produce an
      organoleptically suitable product. Triticale also was found to be an unacceptable
      substrate for the production of a tempeh-like product. Although the fermented
      wheat product had a desirable aroma and flavor, it lacked patty integrity and
      crumbled when sliced. Further research is needed to evaluate the economic
      significance and industrial applications of these tempeh-like products.

PMID- 8267863
TI  - Feasibility of hepatocellular transplantation via the umbilical vein in prenatal
      and perinatal lambs.
AB  - Hepatocellular transplantation has previously been performed in experimental
      animals by infusion of hepatocyte suspensions into the spleen or portal venous
      system. Cells injected into these sites flow to the liver and engraft within the
      hepatic parenchyma. We designed this study to evaluate the feasibility of
      hepatocellular transplantation through the umbilical vein in the prenatal or
      perinatal periods. Allogeneic sheep hepatocytes were harvested, stained with the
      vital fluorescent dye DiI, and injected into the umbilical vein of fetal lambs at
      85% gestation and term. Hemodynamic studies performed to assess the physiological
      impact of transplantation on the recipient animal demonstrated that the procedure
      was well tolerated. No significant short-term complications were encountered and
      no lesions were found by conventional histological examination at necropsy 1-17
      days after transplantation. Engrafted cells were identified within the liver by
      fluorescent microscopy and flow cytometry in 4/7 animals constituting 1.2-5% of
      the hepatocyte population. Fluorescent cellular material with the morphology of
      hepatocytes, noncellular material, and fluorescent phagocytic cells were seen
      occasionally in other organs including lung, brain, adrenal, and placenta. These
      studies demonstrate the feasibility of performing hepatocellular transplantation
      in the fetus via the umbilical vein in experimental animals.

PMID- 8267864
TI  - Antenatal diagnosis of tetralogy of Fallot with absent pulmonary valve
      accompanied by hydrops fetalis and polyhydramnios.
AB  - The case presented is an antenatal diagnosis of tetralogy of Fallot with absent
      pulmonary valve which was accompanied by hydrops fetalis and polyhydramnios with
      an absent stomach echo. Absent pulmonary valve was diagnosed by a cystic,
      pulsatile, aneurysmal dilatation of pulmonary arteries and a relatively small
      pulmonary valve annulus without a definite valve echo, in which a typical to-and
      fro flow pattern was detected by the Doppler flow analysis. We will discuss some
      plausible roles of the grossly enlarged pulmonary arteries on hydrops fetalis and
      polyhydramnios.

PMID- 8267865
TI  - Hematologic values of fetal blood obtained by means of cordocentesis.
AB  - Fetal blood values were evaluated from 541 cordocenteses. Simple regressions were
      used to find a correlation between blood values and gestational age. We found a
      linear increase in hemoglobin concentration and hematocrit throughout gestation;
      a linear decrease of the mean corpuscular volume with the gestation was evidenced
      as a regular decrease in mean corpuscular hemoglobin. Lastly, the mean
      corpuscular hemoglobin concentration was constant during the gestation; a linear
      increase of the platelet count and the nucleated cells was also evidenced. We
      suggest that each fetal medicine unit should have its own reference ranges. It
      will permit to accurately diagnose fetal infection, fetal anemia, or any fetal
      disease where alterations of hematopoiesis have been described.

PMID- 8267866
TI  - Measurement of adult hemoglobin in fetal blood samples by high-performance liquid
      chromatography as purity control for the prenatal diagnosis of chromosomal
      abnormalities.
AB  - This study was aimed at testing if measurement of adult hemoglobin (HbA) by ion
      exchange high-performance liquid chromatography could serve as a purity control
      of fetal blood samples. We studied 240 samples obtained for karyotyping by
      cordocentesis under ultrasound guidance. Mean red cell volume (MCV), red cell
      distribution width (RDW) and HbA were measured on each sample. HbA was determined
      from 5 microliters of blood in 8 min. From 18 to 30 weeks of gestation, HbA
      values in fetal blood do not vary and are tightly clustered around 5.4%
      (SD:1.1%). After 30 weeks, HbA increases as the fetal to adult switch begins.
      Experimental contaminations of fetal blood by maternal blood show that HbA
      variations are more pronounced than MCV or RDW variations. A 5% contamination is
      readily detected. This approach is rapid, sensitive and reliable. Incidentally,
      it readily detects the presence of an abnormal hemoglobin.

PMID- 8267867
TI  - Consequences of misdiagnosis of intrauterine growth retardation for preterm
      elective cesarean section.
AB  - We studied the consequences of misdiagnosis of intrauterine growth retardation
      (IUGR) for preterm elective cesarean section among live singleton newborns in two
      teaching hospitals in Paris between 1978 and 1983. The population studied
      comprised the 16,540 babies who were normal for date, according to the 10th
      percentile of the reference curve established in this population. For 118 of
      these infants, IUGR had been diagnosed during pregnancy. The preterm elective
      cesarean section rate was 12.7% among newborns for whom IUGR was erroneously
      diagnosed, compared to 1.2% among those for whom IUGR was not diagnosed. The
      relationship between preterm cesarean section and misdiagnosis of IUGR still
      existed (odds ratio: 5.2, 95% CI: 2.1-12.9) after taking into account obstetric
      history and hypertension during pregnancy. Our results show that after diagnosis
      of IUGR, supplementary tests are essential to confirm fetal distress and
      consequently avoid unnecessary interventions.

PMID- 8267868
TI  - Successful treatment of primary fetal hydrothorax by long-time drainage from week
      23. Case report and review of the literature.
AB  - We report on a case of unilateral primary fetal hydrothorax leading to
      nonimmunological fetal hydrops (NIHF). The NIHF was treated successfully by
      inserting two consecutive intrauterine catheters at 23 weeks gestation. The first
      catheter was dislocated through the uterine wall to the maternal peritoneal
      cavity. At 36 weeks gestation, the mother had a spontaneous onset of labor after
      premature rupture of membranes and a normal vaginal delivery of a healthy infant
      with good perinatal outcome. Shunting of PFHT has rarely been described up to
      now. This case report supports observations of previous authors that early
      shunting of pleural effusions may prevent progression of NIHF as well as
      postnatal pulmonary hypoplasia. Unexpected perinatal complications of fetus,
      mother or both should not be neglected.

PMID- 8267869
TI  - Fetal hemangiolymphangioma: a case report.
AB  - Hemangiolymphangioma is a malformation of both lymphatic and blood vessels. We
      present a case of fetal abdominal hemolymphangioma diagnosed by ultrasound at 27
      weeks of gestation. The extensive fetal involvement, and the diagnosis before
      fetal viability led us to propose medical termination of pregnancy. This
      represents the second reported case of prenatal diagnosis of this malformation.

PMID- 8267870
TI  - Wear rates of artificial denture teeth opposed by natural dentition.
AB  - The wear rate of polymeric or composite-based artificial denture teeth on fixed,
      removable and implant prostheses is important in the maintenance of cuspal form,
      masticatory efficiency and occlusal stability. A servo-hydraulic based artificial
      mouth in which an occlusion was established between artificial denture teeth, and
      the palatal cusp of a human maxillary third molar was established and used to
      assess the wear resistance of 5 artificial denture tooth materials. Volumetric
      wear was determined for Dentsply Trublend SLM, Dentsply IPN, Vita Vitapan,
      Ivoclar Orthotyp and Ivoclar Orthosit denture teeth. Scanning electron microscopy
      was also done to assess the textural character of the wear facets of each denture
      tooth sample. The lowest volume loss was observed for Trublend SLM followed by
      IPN, Orthotyp, Vitapan and Orthosit. Textural assessment of the materials was
      consistent with the objective wear data.

PMID- 8267871
TI  - A comparison of the Braun Oral-B Plaque Remover (D5) electric and a manual
      toothbrush in affecting gingivitis.
AB  - This three-month clinical trial was designed to compare the effect of an electric
      and a manual toothbrush on reducing primarily gingivitis and secondarily, plaque,
      in a cohort of 70 healthy adults. After baseline evaluation of gingivitis, soft
      tissue trauma, and plaque, patients were randomly assigned to one of the two
      experimental groups, shown an instructional tooth brushing videotape, and had
      their teeth cleaned. Soft tissue trauma was again scored at 2 weeks. At 12 weeks
      all three clinical parameters were again evaluated. The results showed
      statistically significant reductions (baseline vs. 3-month) in both whole mouth
      (p = 0.003) and interproximal (p = 0.008) gingivitis scores for the electric
      toothbrush group. No significant reduction at three months compared to baseline
      was seen for the manual brush group. When gingivitis reductions were compared
      over the three-month test period, the electric brush was significantly better
      than the manual toothbrush in both whole mouth (p = 0.0007) and interproximal (p
      = 0.002) gingivitis reduction. No increase in soft tissue trauma and no
      significant differences in plaque reductions were seen for either toothbrush.

PMID- 8267872
TI  - Analgesic onset time as a measure of topical anesthetic efficacy in spontaneous
      toothache pain: a pilot study.
AB  - The purpose of this pilot investigation was to determine the usefulness of
      analgesic onset time as a measure of topical anesthetic efficacy in patients with
      spontaneous toothache pain. Under blinded conditions, 20 patients with
      spontaneous toothache pain from an open tooth cavity were randomly assigned to
      receive either 20% benzocaine or placebo (80% polyethylene glycol). The
      medication was applied directly to the open cavity in a volume of 3 drops.
      Patients then depressed a stop watch when they initially experienced pain relief.
      Patients who did not obtain relief were assigned the maximum onset value of 600
      seconds. The average analgesic onset time was 111.8 seconds in the benzocaine
      group and 289.0 seconds in the placebo group. In the benzocaine group, 90% of the
      patients reported some pain relief, while a surprisingly high 60% reported some
      pain relief in the placebo group. The results of this study suggest that in the
      spontaneous toothache pain model, analgesic onset time is a valuable measure of
      topical anesthetic efficacy. In addition, polyethylene glycol at a concentration
      of 80% may not be a totally inactive vehicle.

PMID- 8267873
TI  - Dentifrice abrasiveness on microfill composite resin and dentin: a comparative
      study.
AB  - This in vitro study evaluated the abrasiveness of seven dentifrices on microfill
      composite resin discs and dentin surfaces. The composite resin discs and dentin
      surfaces were brushed in groups using slurries of the different dentifrices. Each
      specimen was subjected to 2400 strokes using medium bristle toothbrushes at a
      brush tension of 150 g. Any changes in surface roughness were noted through the
      use of a mechanical profiler or profileometer and scanning electron micrographs.
      The results of this study have indicated that Rembrandt Whitening Toothpaste was
      significantly less abrasive to the microfill composite discs and dentin surfaces
      compared to the other dentifrices tested (p < .05, ANOVA). Further clinical
      studies may be warranted to test the abrasiveness of dentifrices, especially if
      they are used over extended periods of time.

PMID- 8267874
TI  - Bristle end-rounding in children's toothbrushes: a comparative study.
AB  - Animal and clinical studies have shown that sharp, unpolished toothbrush bristles
      can injure gingival tissues and that substantial variation exists in the degree
      of end-roundness of commercially available toothbrushes. In this study, eight
      brands of children's toothbrushes were assessed for their relative potential to
      cause oral tissue injury based upon the degree of end-roundness of their
      bristles. The brands studied were: Blend-a-dent Jr., Butler GUM Jr., Colgate Plus
      Jr., Johnson & Johnson Prevent Jr., Johnson & Johnson Reach Child, Lever Bros.
      Disney, Oral-B P20, and Sensodyne Jr. Brushes were ranked on the basis of three
      criteria: the percentage of bristles with sharp ends (89% roundness or less), the
      percentage of bristles with smooth edges (96% roundness or greater), and the
      average roundness of bristle ends. The Oral-B P20 brush had significantly more (p
      < 0.05) bristles with a roundness of 96% or greater; it also was in the group
      having the lowest number of bristles with sharp edges and had the highest average
      roundness. Based on these criteria, the Oral-B P20 showed the least potential for
      oral tissue damage, whereas the Johnson & Johnson Reach Child and Butler GUM Jr.
      showed the most potential for tissue injury. The other brands investigated were
      intermediate in end-rounding values and damage potential.

PMID- 8267875
TI  - Laboratory and clinical evaluations of the Jordan Exact toothbrush.
AB  - A new toothbrush, the Jordan Exact, has been compared with a flat multitufted
      toothbrush, the Oral-B 35 toothbrush. In a laboratory study the Jordan Exact
      toothbrush had significantly higher interproximal access, compared to the Oral-B
      35, combining all toothbrushing pressures tested, using either vertical or
      horizontal brushing motions on simulated molar teeth. Clinical safety and
      efficacy were evaluated in a 30-day single blind study. Evaluations of plaque
      mean scores were recorded before and after a one minute brushing at baseline, day
      15 and day 30. At the same time periods, assessments of irritation, gingivitis
      and bleeding on probing were conducted. No oral irritation from either toothbrush
      was observed or reported throughout the test period. At all examinations there
      were no significant differences in overnight plaque scores. After brushing, an
      analysis of covariance on plaque area scores revealed that the Jordan Exact
      toothbrush removed significantly more plaque than the Oral-B 35 toothbrush. By
      day 30, the Jordan Exact toothbrush significantly reduced gingivitis on buccal
      surfaces but no significant change was observed in the Oral-B 35 group. Subjects
      using the Jordan Exact toothbrush had a significant decline in bleeding on
      probing; subjects in the Oral-B 35 toothbrush group had no significant change
      over the 30 days of the study.

PMID- 8267876
TI  - 17th Fritz Lipmann Lecture. Wanderings (wonderings) in metabolism.
AB  - Two of the most recent hypotheses concerning metabolism and its regulation are
      examined. First, the theory of distributive regulatory control of metabolic
      pathways is considered in light of experimental evidence concerning the lack of
      change in flux of a pathway when individual enzymes are either increased or
      decreased. In addition, it is known that when flux through pathways is either
      increased or decreased, one finds that the amount of all the enzymes of that path
      increase or decrease simultaneously. Second, the hypothesis of the existence of
      metabolons, complexes of sequential metabolic enzymes, is examined using the
      Krebs TCA cycle pathway as an example. The evidence from in vitro studies with
      pure enzymes to in vitro metabolic studies with yeast mutants is reviewed and
      evaluated. Unsolved problems concerning these hypotheses which still exist are
      considered.

PMID- 8267877
TI  - On the specificity of carboxypeptidase N, a comparative study.
AB  - The structure of the enzymatically active subunit of human plasma
      carboxypeptidase N was modeled based on the homology with bovine carboxypeptidase
      A. The active site of carboxypeptidase N is well conserved in comparison with
      carboxypeptidase A. From a comparison of energetically favorable binding sites
      for different atomic probe groups a hypothesis for the differences in substrate
      specificity between carboxypeptidases A and N was derived. Small synthetic
      peptide substrates were synthesized to confirm this hypothesis. This study shows
      that even with very low homology model building by homology can be employed to
      build models of sufficient quality to aid in drug design.

PMID- 8267878
TI  - Glycine-rich analogues of Cucurbita maxima trypsin inhibitor (CMTI-III)
      substituted by valine in position 27 display relatively low antitrypsin activity.
AB  - Five new analogues of the trypsin inhibitor CMTI-III were synthesized by the
      solid-phase method. All analogues containing a valine residue in position 27 and
      glycine residues in some or all of the positions 9, 11, 14, 17, 19, 29 as well as
      in two cases a norleucine residue in position 8 displayed association equilibrium
      constants by 6-7 orders of magnitude lower than the native CMTI-III inhibitor.

PMID- 8267879
TI  - A novel chymotrypsin-like serine proteinase from human lung.
AB  - A novel chymotrypsin-like serine proteinase with an M(r) of 30,000 has been
      isolated from human lung tissue. The enzyme was active on both the synthetic
      substrate Suc-Ala-Ala-Pro-Phe-SBzl and azocasein, with a pH optimum of 8.0 and a
      preference for high concentrations of NaCl for maximum activity. The proteinase
      was inhibited by diisopropylfluorophosphate, tosyl-phenylalanyl-chloromethane,
      chymostatin, soybean trypsin inhibitor, alpha-1-antichymotrypsin, and alpha-2
      macroglobulin. It was not inhibited by C-1 inhibitor or aprotinin. An N-terminal
      sequence of IIGGTESKPDSRPYMALLQIVEPAVH indicated that this enzyme is a member of
      a superfamily of serine proteinases comprising cathepsin G, chymase, and the
      granzymes; however, it is clearly distinct from these enzymes on the basis of
      both physical and chemical properties.

PMID- 8267880
TI  - Distinction of structural reorganisation and ligand binding in the T<==>R
      transition of insulin on the basis of allosteric models.
AB  - Two allosteric models are presented for the T<==>R transition of insulin hexamers
      in the presence of phenolic ligands which are based on existing experimental
      information. The transition mainly involves residues 1-8 of the B-chain, i.e. 15%
      of the molecule, which are extended in the T- and helical in the R-state. The
      main facts to be accounted for are: 1) the transition is undergone trimer-wise;
      2) the transition of the second trimer is disadvantaged compared to the first
      one; 3) the subunits of a trimer undergo transition in a cooperative process; 4)
      binding sites for phenolic ligands only exist in R3 trimers; 5) ligands shift the
      equilibrium by arresting the R-state; 6) the ligand is accommodated in a pocket
      made up between two adjacent subunits; 7) binding one ligand molecule extends the
      lifetime of the two other binding sites of a trimer; 8) only ligand-free trimers
      can undergo transitions. The two models allowed for CD spectroscopic titrations
      of zinc and cobalt insulin with phenol and m-cresol to be assessed in terms of
      structural reorganisation and ligand binding, and for the respective standard
      free energy differences to be calculated. delta G degrees for the reorganisation
      of the first timer in zinc-insulin is about 8 kJ/mol, and for that of the second
      trimer, 21kJ/mol. The corresponding values for cobalt-insulin are 12 and 24
      kJ/mol, respectively. For both zinc- and cobalt-insulin, the delta G degrees for
      phenol and m-cresol binding is about -18 kJ/mol. Both models are equally
      compatible with the titration data.

PMID- 8267881
TI  - Time course of lectin and storage protein biosynthesis in developing pea (Pisum
      sativum) seeds.
AB  - Lectins and storage proteins from pea (Pisum sativum) and other Leguminosae seeds
      interact in vitro. In order to evaluate whether this relationship may be
      important also in vivo, the time course of biosynthesis of these proteins in
      developing pea seeds was followed. The proteins appear in the following temporal
      order: vicilin-lectin-convicilin-legumin. The time course of protein synthesis
      was also followed by the subcellular morphological changes occurring
      simultaneously. The appearance of vicilin coincides with the formation of
      regularly shaped protein globules within the vacuole. Immediately after the start
      of lectin synthesis, these globules flatten and begin to adhere to the inner
      membrane surface of the vacuole. Legumin appears at a time when the vacuoles
      already have largely disappeared in favour of smaller vesicles which eventually
      develop into protein bodies. These results together with previous findings are
      consistent with the view that one of the biological functions of the lectin may
      consist in serving as a link between vicilin and the inner face of the vacuole
      membrane.

PMID- 8267882
TI  - Purification and characterization of the biologically active human truncated
      macrophage colony-stimulating factor expressed in Saccharomyces cerevisiae.
AB  - A human truncated macrophage colony-stimulating factor (M-CSF) cDNA encoding
      amino acid residues from 3 to 149 of the native M-CSF was isolated by using the
      polymerase chain reaction. When introduced into Saccharomyces cerevisiae by a
      general secretion vector pVT 102u/alpha, it directs the expression of the
      biologically active dimeric form of M-CSF. Through the 3 stages of purification,
      i.e. concentration by DEAE-cellulose column chromatography, hydrophobic
      chromatography on phenyl-sepharose and Mono Q fast protein liquid chromatography,
      the recombinant truncated M-CSF was purified as to exhibit a specific activity of
      1.02 x 10(7) units/mg of protein. SDS-PAGE of this purified truncated M-CSF
      showed that its apparent molecular mass is 22 kDa under reducing conditions.

PMID- 8267883
TI  - Editing British neurosurgery.

PMID- 8267884
TI  - Post-operative mortality in acute extradural haematoma.

PMID- 8267885
TI  - Extradural haematoma: trends in outcome over 35 years.
AB  - We have reviewed 35 years experience of extradural haemorrhage (EDH) in a large
      neurosurgical unit, based in two university hospitals, one dealing exclusively
      with children and the other a general hospital. A steady reduction in the
      mortality rate from 29 to 8.5% occurred during that period. A trend towards
      earlier diagnosis is noted and an increasing proportion of rural patients has
      been evident throughout the study period. During the time-period studied there
      were many significant developments: the establishment of a modern neurosurgical
      unit, the evolution of an intensive care unit, the availability of CT head
      scanning and the formal organization of rapid retrieval to service country areas.
      However, no single feature could be identified as the major contributor to
      falling mortality results. Clinical awareness and early diagnosis are the keys to
      successful management of EDH.

PMID- 8267886
TI  - Management of spinal astrocytoma with conservative surgery and radiotherapy.
AB  - Twenty-seven patients with histologically verified spinal astrocytoma were
      treated at the Royal Marsden Hospital with postoperative radiotherapy. All
      patients had previous surgery; 10 had partial resection and 17 biopsy alone. All
      patients received involved field radiotherapy to a median dose of 50 Gy in 33
      fractions. Overall 5- and 10-year survival was 59 and 52%, and progression free
      survival was 38 and 26% at 5 and 10 years, respectively, at a median follow-up of
      6.5 years. Following radiotherapy, eight patients showed functional improvement,
      15 were unchanged and two deteriorated. Sixteen patients relapsed, eleven at the
      primary site and five elsewhere in the CNS. Low grade histology, female gender
      and the presence of intramedullary cysts were favourable prognostic factors for
      survival on univariate analysis. The extent of surgery was not a significant
      predictor of survival. It is not possible to define the precise role of
      radiotherapy. However, all patients had residual tumour prior to irradiation, and
      53% of low grade and 33% of high grade gliomas remained controlled locally at 3
      years with stabilization or improvement in neurological function in all but two
      patients. This suggests that radiotherapy may result in temporary disease control
      analogous to cerebral gliomas.

PMID- 8267887
TI  - Surgical treatment of brachial plexus injuries.
AB  - Ninety-nine consecutive patients with brachial plexus injuries were operated upon
      over a period of 8 1/2 years. Among them, 70% sustained traction injuries. The
      surgical procedures included neurolysis in 35, excision of a lateral neuroma in
      six and interfascicular sural nerve grafting in 27 patients. In 25 patients,
      after an exploration, no further surgical procedure was carried out. In four
      patients, an intercosto-musculocutaneous anastomosis, and in two a trapezius
      muscle transplant were carried out. Just over two-thirds (68%) of the patients
      were operated upon 6 months after the injury. Water soluble contrast myelography
      was performed in 60 patients. These included patients where a root injury had
      been diagnosed clinically or electrophysiologically. MRI was performed in 14
      patients to visualize root avulsions and distal lesions. Operative confirmation
      of MRI findings were obtained in more than 85% of patients. While an early
      improvement was seen in patients where only a neurolysis was required, at longer
      follow-up, gratifying results were recorded even in patients with interfascicular
      grafts of 6-8 cm length. All 49 patients who came for follow-up and in whom a
      definitive surgical procedure had been carried out improved. Of these patients,
      61% showed near normal or satisfactory functional recovery. The other patients
      were followed for periods of less than 1.5 years and may show further improvement
      with time.

PMID- 8267888
TI  - Antibiotic prophylaxis in unrepaired CSF fistulae.
AB  - The value of antibiotic prophylaxis in patients with Cerebrospinal Fluid Leakage
      (CSF) is debatable. The aim of this study was to determine the value of
      prophylactic antibiotics in these patients. The study population comprised 253
      patients with definite CSF leaks, of whom 106 received adequate antibiotic
      prophylaxis (Group A) and 109 were not treated with antibiotics (Group B). Thirty
      eight patients were excluded from the analysis because they received antibiotics
      for reasons other than the CSF leakage. The two groups were closely matched for
      age, sex, type of CSF fistula, site, and duration of CSF leakage and presence or
      absence of skull fractures, but there were more patients with facial fractures
      and pneumocephalus in those who were treated with antibiotics. The first week
      meningitis rate was 6.6 and 9.17% in the treated and untreated groups,
      respectively, while the annual risk of meningitis was 7.6% in the treated and
      11.9% in the untreated group. However, these differences did not reach
      significance (P > 0.05). The survival curves of meningitis-free survival were
      similar in the two groups, particularly during the first 4 weeks during which
      antibiotics were given (Log Rank test, p > 0.05). Furthermore, there were more
      cases of Gram-negative infection and of partially-treated meningitis in the
      treated group. Although this was a retrospective, non-randomized study, it
      confirms the conclusions of previous smaller series, that prophylactic
      antibiotics do not significantly reduce the risk of meningitis in these patients.
      It is ethically justifiable to withhold antibiotic prophylaxis in patients with
      CSF fistulae until a prospective controlled double blind trial has settled the
      question.

PMID- 8267889
TI  - Rapid resolution of visual abnormalities with medical therapy alone in patients
      with large prolactinomas.
AB  - Large prolactin-secreting pituitary adenomas with suprasellar extension are often
      complicated by visual field defects, for which surgical decompression is the
      accepted treatment. However, surgical management of large prolactinomas is often
      not curative. This report describes a group of six unselected male patients who
      presented with visual field defects and reduced visual acuity due to large
      pituitary tumours with suprasellar extension. All six patients also had loss of
      libido and/or impotence. A rapid serum prolactin estimation enabled the diagnosis
      of prolactinoma to be made, and CT revealed a large pituitary adenoma with
      suprasellar extension. The patients were treated with bromocriptine, in doses
      increasing from 2.5 to 20 mg daily, as the sole therapy. Symptoms were relieved
      and serum prolactin levels were restored to normal or near normal; visual field
      defects resolved and visual acuity recovered in all patients. A repeat CT showed
      evidence of tumour shrinkage especially of the suprasellar extension, in all the
      patients. A diagnosis of prolactinoma should always be considered in a patient
      with a large pituitary tumour. The clinical history and a rapid prolactin assay
      will confirm the diagnosis. Treatment with bromocriptine leads to rapid
      improvement in perimetry and visual acuity as well as tumour shrinkage, obviating
      the need for pituitary surgery.

PMID- 8267890
TI  - Intracranial and orbital cavernous angiomas: a review of 74 surgical cases.
AB  - We present a surgical series of 74 patients (30 males and 44 females) with
      pathologically verified cavernous angiomas of the intracranial and orbital
      compartments. Patients were admitted between 1975 and 1991; six had a family
      history of cerebral cavernomas, and two had multiple (two) lesions. The 76
      malformations were located as follows: 57 were in the cerebral hemispheres, four
      in the supratentorial ventricles, one was in the middle cranial fossa, two were
      in the brain stem, five in the cerebellum and seven in the orbits. Seizures and
      focal neurological deficits, and decrease of visual acuity with exophthalmus,
      were the main clinical signs observed in patients with intracranial and orbital
      cavernomas, respectively. Sixteen patients (21.6%) had a clinically significant
      haemorrhage attributable to the cavernous angioma. A number of these vascular
      malformations were misdiagnosed by computed tomography. In the last 10 years
      magnetic resonance imaging has been the most sensitive method for detecting these
      lesions. Seventy-four of the 76 diagnosed cavernomas were treated surgically: a
      complete excision was obtained in 68 patients; in two patients with multiple
      lesions only those causing symptoms were removed. Surgery for the 10 deep lesions
      was aided considerably by stereotactic localization. Two patients died in the
      immediate postoperative course. The overall outcome was good in 66 of the 72
      remaining patients, resulting in improved seizure control or lessened
      neurological deficit.

PMID- 8267891
TI  - CT measurement of the ventricular catheter length in shunt surgery.
AB  - When inserting a ventricular shunt, the length of the ventricular catheter is a
      deciding factor in the avoidance of complications. The author has devised a
      standardized method of determining this length which has been shown to achieve
      consistently successful results. It is determined from the CT scan scout film of
      the individual patient with hydrocephalus. The length is half the distance
      between the external auditory meatus and the mid-point of the coronal suture of
      the skull. The catheter is inserted by the frontal approach and is directed
      perpendicular to the skull, aiming at the inner canthus of the ipsilateral eye.
      The burrhole is located in the same parasagittal plane as the pupil either in
      front of or behind the coronal suture. The catheter tip has been demonstrated by
      repeated follow-up CT scans to lie just anterior to the foramen of Monro. This
      method was used in 175 patients and it proved to be highly successful.

PMID- 8267892
TI  - Anterior cervical decompression and fusion using the Coventry cervical spreader
      and dowel inserter.
AB  - Instrumentation for use in anterior cervical interbody fusion is described which
      allows controlled spreading of the adjacent vertebrae and accurate placement of
      the dowel. A portion of our experience with this instrument is analysed to
      support our belief that it is safer and more effective than conventional
      spreaders with a lower risk of damage to the graft or surrounding structures.

PMID- 8267893
TI  - Chondromas of the spine: report of two cases and review of the literature.
AB  - We report two cases of vertebral chondroma presenting with spinal cord
      compression. In one case there was ultimate malignant transformation.

PMID- 8267894
TI  - Spinal subarachnoid haemorrhage from an "ancient" schwannoma of the cervical
      spine.
AB  - A case of spinal subarachnoid haemorrhage secondary to degenerative changes in a
      cervical schwannoma is presented. The problems associated with diagnosis as well
      as the possible mechanisms resulting in haemorrhage from spinal tumours are
      reviewed.

PMID- 8267895
TI  - Beware the clunking neck: a report of two cases.

PMID- 8267896
TI  - Intracranial squamous cell carcinoma arising in an epidermoid cyst.
AB  - Intracranial epidermoid cysts are uncommon benign tumors of developmental origin;
      malignant transformation is extremely rare. We report a case of squamous cell
      carcinoma arising in a chiasmatic-parasellar epidermoid cyst. Malignant change
      had not been suspected until histological examination revealed it.

PMID- 8267897
TI  - Hyperprolactinaemia and infertility following cranial irradiation for brain
      tumours: successful treatment with bromocriptine.
AB  - Two young women developed oligomenorrhoea and galactorrhoea 4 and 7 years after
      whole brain irradiation for brain tumours. Both had mild hyperprolactinaemia due
      to irradiation-induced hypothalamic damage. In both patients, oral bromocriptine
      normalized prolactin levels and menstruation resumed. One patient then had a
      successful pregnancy.

PMID- 8267898
TI  - Intracranial aneurysm formation following radiotherapy.
AB  - Two patients sustained a subarachnoid haemorrhage secondary to radiation-induced
      vasculopathy and associated aneurysm. A 65-year-old woman was treated by
      radiotherapy for a stereotactically biopsied left parieto-temporal astrocytoma.
      Three-and-a-half years later, she suffered a subarachnoid haemorrhage secondary
      to a giant aneurysm arising from the middle cerebral artery bifurcation. A 44
      year-old man sustained a subarachnoid haemorrhage 21 years after receiving whole
      brain irradiation for a large left parietal angioma. Angiography following his
      subarachnoid haemorrhage revealed a distal right middle cerebral artery aneurysm
      that was not visible on earlier angiograms. Both patients underwent craniotomy
      for their aneurysms with good postoperative recoveries.

PMID- 8267899
TI  - Tuberculous granuloma of the clivus.
AB  - We report the clinical features of a middle-aged man who presented with multiple
      cranial nerve dysfunction and who, on computed tomography (CT) and magnetic
      resonance (MR) imaging, proved to have a lesion of the clivus extending down to
      the body of the axis. Biopsy and limited excision showed this to be a tuberculous
      granuloma which grew M. tuberculosis on culture.

PMID- 8267900
TI  - The anterior interhemispheric trephine approach to anterior midline aneurysms.

PMID- 8267901
TI  - Methods development toward the measurement of polyaromatic hydrocarbon-DNA
      adducts by mass spectrometry.
AB  - The measurement of DNA adducts in human samples is at an early stage. The
      accuracy of some of the current measurements is not defined, the structures are
      unknown for a significant number of the adducts that have been detected, and
      there is little information about how many adducts remain to be discovered. This
      is due largely to the trace amounts of human DNA adducts in any sample. A
      consequence of this is that the true potential of DNA adducts as indicators of
      exposure and risk in human toxicology is far from realized. Mass spectrometry, a
      powerful technique for organic analysis, is the key to exploiting fully the
      usefulness of human DNA adducts as biomarkers of human exposure and risk. Mass
      spectrometry can make accurate measurements, discover unknown compounds, and
      determine the structures of these unknown compounds. However, the trace (very
      small) amounts of human DNA adducts have limited mass spectrometry's usefulness
      in analyzing such samples. This project focused on increasing the sensitivity of
      mass spectrometry for measuring human DNA adducts. Advances in sensitivity have
      been achieved for two modes of mass spectrometry applied to standards related to
      DNA adducts: gas chromatography with electron-capture negative ion mass
      spectrometry, and fast-atom-bombardment mass spectrometry. These advances involve
      both sample preparation and instrument conditions.

PMID- 8267902
TI  - Pneumocystis carinii: recent advances in basic biology and their clinical
      application.

PMID- 8267903
TI  - Complement activation upon binding of mannan-binding protein to HIV envelope
      glycoproteins.
AB  - OBJECTIVE: Retroviruses can activate the complement system in the absence of
      antibodies, and the purpose of this study was to examine whether the serum
      collection, mannan-binding protein (MBP), could mediate such complement
      activation. DESIGN: Virus envelope proteins gp120 and gp110 from HIV-1 and HIV-2
      were incubated in microtitre wells coated with anti-gp120 or anti-gp110
      antibodies. After further incubation with serum, complement activation was
      measured as deposition of complement factor C4 and C3 onto the wells. Deposited
      C4 and C3 were detected with enzyme-labelled antibodies. Normal human serum
      depleted of endogenous lectins by affinity chromatography was used as the
      complement source. Serum from C1q-deficient patients was used in some
      experiments. Complement activation was then assessed with and without prior
      addition of MBP to the wells. Complement activation was also correlated with the
      quantity of endogenous MBP in a number of normal sera. RESULTS: Complement
      activation by HIV envelope glycoproteins was found to be mediated by the binding
      of MBP to carbohydrates on natural envelope protein produced in virus-infected
      cells, as well as on glycosylated recombinant envelope proteins produced in
      insect cells. Non-glycosylated recombinant envelope proteins produced in
      Escherichia coli did not induce this type of complement activation. CONCLUSIONS:
      Activation of the classical complement pathway by retrovirus envelope proteins
      can be initiated by the binding of MBP to carbohydrate side chains of envelope
      glycoproteins.

PMID- 8267904
TI  - Immunization of human HIV-seronegative volunteers with recombinant p17/p24:Ty
      virus-like particles elicits HIV-1 p24-specific cellular and humoral immune
      responses.
AB  - OBJECTIVE: To evaluate the immune response to HIV-1 p24 generated in vivo by
      p17/p24:Ty virus-like particles (p17/p24:Ty-VLP) by examining the
      lymphoproliferative and antibody (Ab) responses to HIV-1 p24, as well as Gag
      specific cytotoxic T lymphocytes (CTL), in HIV-seronegative volunteers immunized
      with hybrid p17/p24:Ty-VLP. DESIGN AND METHODS: Sixteen HIV-seronegative
      volunteers were immunized with p17/p24:Ty-VLP at two dose levels (100 or 500
      micrograms) and monitored for the following 48 weeks for production of anti-p24
      and anti-p17 Ab, in vitro lymphoproliferative responses to HIV-1 p24 and p17, and
      in vitro CTL responses to HIV-1 Gag. RESULTS: Twelve out of the 16 volunteers had
      significant p24-specific proliferative responses, with volunteers on the higher
      dose schedule exhibiting earlier proliferative responses than those on the lower
      dose schedule. Proliferative responses in both volunteer groups were similar in
      overall magnitude but appeared at different times during the immunization
      schedule. Anti-p24 Ab were detected in six out of the nine individuals in the
      lower dose group and in five out of the seven in the higher dose group. There was
      a good correlation between the presence of p24-specific Ab and the detection of
      lymphoproliferative responses to the p24 protein in peripheral blood mononuclear
      cells isolated from the same individuals. Anti-p17 Ab were detected in five
      volunteers. No Gag-specific CTL responses were detected. CONCLUSION: We conclude
      that hybrid HIV-1 p17/p24:Ty-VLP are capable of inducing both cellular and
      humoral immunity to HIV-1 Gag p17 and p24 components and are worthy of further
      study as a potential HIV immunotherapeutic.

PMID- 8267905
TI  - Improved detection of serum HIV p24 antigen after acid dissociation of immune
      complexes.
AB  - OBJECTIVE: To evaluate an acid pretreatment method designed to dissociate HIV p24
      antigen from immune complexes in serum. DESIGN: Patient sera and sera containing
      experimental immune complexes were quantified for p24 antigen before and after
      immune complex dissociation (ICD). The clinical application of ICD was assessed
      in 1328 serum and plasma samples collected from HIV-infected patients. METHODS:
      Immune complexes were created artificially by mixing purified p24 antigen with
      antibody-positive sera or a standardized concentration of human antibody to p24.
      ICD was achieved by incubation of samples with an equal volume of Glycine HCl for
      90 min at 37 degrees C followed by neutralization with Tris NaOH. Samples were
      quantified for p24 antigen using a commercial enzyme-linked immunosorbent assay
      (ELISA) kit. RESULTS: ICD resulted in significant release of purified antigen
      from simulated immune complexes in antibody-positive sera. Variation in antigen
      sequestration and dissociation was related to anti-gag antibody titers. ICD
      resulted in complete recovery of 500 pg of antigen complexed with human anti-p24
      antibody at concentrations up to 2.5 U/ml. In seropositive patients, the mean
      level of serum antigen was 3.5-fold higher after ICD, and an additional 21% were
      antigen-positive. CONCLUSIONS: Pretreatment greatly improved antigen detection in
      HIV-antibody-positive sera by effectively dissociating immune complexes without
      compromising reactivity of the antigen itself. The treatment also facilitated
      routine monitoring of patients by revealing fluctuations in serum antigen that
      were indistinguishable or poorly defined in untreated sera.

PMID- 8267906
TI  - Epstein-Barr virus infection of HIV-seropositive individuals is transiently
      suppressed by high-dose acyclovir treatment.
AB  - OBJECTIVE: To assess whether oral acyclovir can eliminate persistent Epstein-Barr
      virus (EBV) infection and thereby prevent EBV-associated lymphoma development in
      HIV-seropositive homosexual men. METHOD: Persistent EBV infection was examined in
      a group of 21 HIV-seropositive homosexual men before, during and after treatment
      with oral acyclovir at a dose of 800 mg every 6 h (10 individuals) or with a
      placebo (11 individuals). RESULTS: In 13 individuals, EBV was isolated from the
      oropharynx before and after treatment (seven cases from the acyclovir-treated
      group and six from the placebo-treated group). A significant reduction in virus
      isolation occurred during treatment in the acyclovir-treated group, but not in
      the placebo-treated group. In seven cases in whom EBV shedding was detected
      before and after treatment, the EBV strain isolated was identical throughout the
      study, even when acyclovir had abolished detectable shedding for the duration of
      the treatment. In two other cases more than one strain was detected. On
      examination of the EBV type present, 89% of a group of 18 patients consistently
      shed type A virus, 5.5% type B virus and 5.5% showed evidence of co-infection
      with both virus types. This compares with figures of 100, 0 and 0%, respectively,
      in a control group of HIV-seronegative individuals. CONCLUSIONS: High-dose
      acyclovir therapy does not eliminate persistent EBV infection from the oropharynx
      of healthy HIV-seropositive individuals and therefore would not necessarily
      prevent lymphoma development. Our results suggest that infection by type B EBV,
      and co-infections of both A and B type, are more common in HIV-seropositives than
      HIV-seronegatives.

PMID- 8267907
TI  - A prospective study of the risk of tuberculosis among HIV-infected patients.
AB  - OBJECTIVE: To evaluate the risk of developing active tuberculosis (TB) in a
      cohort of HIV-1-infected patients. METHODS: Prospective longitudinal follow-up of
      839 HIV-infected patients, of whom 505 (60%) were parenteral drug users and 269
      (32%) homosexual men. Tuberculin skin tests were performed at baseline and
      annually thereafter. Prophylaxis with isoniazid (300 mg daily for 9 months) was
      offered to those with a positive tuberculin test (induration > or = 5 mm).
      Diagnosis of TB was accepted if it could be confirmed microbiologically (acid
      fast bacilli seen in Ziehl-Neelsen stains or grown in Lowenstein-Jensen cultures)
      or pathologically (presence of caseating granulomas) and patients had consistent
      clinical manifestations. RESULTS: Active TB developed in 23 out of the 733 (3.1%)
      patients with a negative tuberculin skin test after a mean follow-up of 16 +/- 11
      months (range, 2-52 months), with an estimated cumulative probability of 1.5 and
      7% after 1 and 3 years, respectively (or 2.4 per 100 patient-years). None of the
      87 patients with a negative tuberculin test but a positive Multitest developed
      TB. Conversely, 106 patients had a positive tuberculin skin test (97 at baseline
      and nine who converted during follow-up). Active TB developed in seven out of the
      26 not receiving prophylaxis or in whom prophylaxis had to be discontinued (16.2
      per 100 patient-years), in four out of 61 patients 3-27 months after having
      completed 9 months of prophylaxis with isoniazid (8.9 per 100 patient-years) and
      in none of the 19 still receiving isoniazid. When TB was diagnosed, the mean CD4
      lymphocyte count of the 34 patients who developed it during follow-up was 77 +/-
      103 x 10(6)/l (range, 1-400 x 10(6)/l). CONCLUSIONS: Among HIV-infected patients
      in whom the tuberculin skin test is negative, the risk of developing active TB is
      sufficient to consider prophylaxis if the CD4 count falls below 400 x 10(6)/l, at
      least in those patients with skin anergy living in high-risk geographical areas
      such as Spain. When the tuberculin skin test was positive, isoniazid (9 months)
      provided a 45% protection beyond the period of its administration.

PMID- 8267908
TI  - Frequency of pulmonary tuberculosis in patients undergoing sputum induction for
      diagnosis of suspected Pneumocystis carinii pneumonia.
AB  - OBJECTIVE: To determine the frequency of pulmonary tuberculosis (TB) in patients
      with suspected Pneumocystis carinii pneumonia (PCP). DESIGN: Prospective study of
      sputum specimens from subjects undergoing diagnostic sputum induction for PCP and
      medical chart review. SETTING: University hospital in the Bronx, New York City.
      PATIENTS: A total of 373 consecutive adults with induced sputum specimens
      adequate for acid-fast smear and mycobacterial culture. MAIN OUTCOME MEASURES:
      Direct immunofluorescence for PCP, acid-fast stain, and mycobacterial culture of
      all induced sputum specimens. Determination of demographic characteristics, HIV
      risk factors, and HIV serological status. Clinical and radiographic findings of
      patients with TB. RESULTS: Proven symptomatic HIV infection was present in 251 of
      the 373 (67%) patients prior to sputum induction. PCP was detected in 136 out of
      519 (26%) specimens, Mycobacterium tuberculosis in 10 (1.9%) specimens from nine
      patients. Smear was positive for acid-fast bacilli in nine (1.7%), of which seven
      (78%) grew M. tuberculosis and two (22%) M. avium complex. Pulmonary TB was found
      in nine of the 373 (2.4%) patients [95% confidence intervals (CI), 1.1-4.6].
      Smears were positive for acid-fast bacilli in seven out of 10 (70%) specimens
      with M. tuberculosis compared with two out of 65 (3%) with other mycobacteria (P
      < 0.0001). Of 66 specimens that grew mycobacteria despite negative acid-fast
      smears, three (4.5%) were M. tuberculosis (95% CI, 0-13.3). Of the nine patients
      with TB, six had prior known TB, chest radiographs atypical for PCP, or both; two
      others had positive acid-fast smears. Only a single patient (0.27%; 95% CI, 0
      0.79) had pulmonary TB, which remained unsuspected after acid-fast smear of
      induced sputum. CONCLUSIONS: Pulmonary TB occasionally occurs in patients with
      suspected PCP and in most cases is suggested by medical history, clinical
      findings, or acid-fast stain of induced sputum.

PMID- 8267909
TI  - Disseminated Mycobacterium genavense infection: clinical and microbiological
      features and response to therapy.
AB  - OBJECTIVE: Mycobacterium genavense is a newly described pathogen that causes
      disseminated infection in AIDS. It is difficult to detect and identify due to its
      slow growth and fastidious nature. There is little information available about
      therapy for this new pathogen. We describe clinical and laboratory features and
      response to therapy in four patients with advanced AIDS complicated by
      disseminated M. genavense infection from Denver, Colorado, USA. DESIGN AND
      METHODS: Retrospective analysis of four cases identified in an AIDS clinic
      affiliated with a municipal hospital in Denver, Colorado. Clinical samples were
      inoculated onto BACTEC 12B, Lowenstein-Jensen, and Middlebrook 7H11 media.
      RESULTS: The clinical features mimicked those of disseminated M. avium complex
      infection, with invasion of liver, spleen and lymph nodes with acid-fast bacilli
      (AFB). Acid-fast smears of blood and lymph nodes were positive; there was a
      modest increase in the growth index in BACTEC broth and tiny colonies appeared on
      Middlebrook agar. Patients were treated with combinations of antimycobacterial
      agents. Blood smears and cultures reverted to negative in treated patients. The
      best clinical response was associated with clarithromycin therapy. CONCLUSIONS:
      Disseminated disease due to M. genavense should be suspected among patients with
      the clinical presentation of disseminated M. avium complex infection and low
      growth index on BACTEC cultures for AFB. The diagnosis of M. genavense may be
      facilitated by performing acid-fast stains of samples from BACTEC bottles in such
      individuals. Clarithromycin therapy is associated with clinical improvement and
      clearance of bacteremia.

PMID- 8267910
TI  - Progression of HIV infection among injecting drug users: indications for a lower
      rate of progression among those who have frequently borrowed injecting equipment.
AB  - OBJECTIVE: To study markers of progression in a cohort of HIV-infected
      intravenous drug users (IDU). DESIGN: A prospective epidemiologic study. SETTING
      AND PATIENTS: We studied progression of HIV infection among 126 IDU attending the
      Municipal Health Service in Amsterdam. MAIN OUTCOME MEASURES: Progression was
      defined as a decline of the CD4 cell count to < 200 x 10(6)/l on two consecutive
      follow-up visits or AIDS. RESULTS: Using Cox modelling, the following baseline
      variables were predictive of progression. Enhanced progression was associated
      with: age > 30 years [relative hazard (RH), 7.7 [95% confidence intervals (CI),
      1.7-36.0]], core antibody negativity [RH, 5.3 (95% CI, 1.6-17.6)], CD4 cell count
      [for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% CI, 0.37-5.16); for CD4 cells 200
      350 x 10(6)/l, RH, 9.20 (95% CI, 2.73-31.05) compared with a CD4 count > 500 x
      10(6)/l]. A lower rate of progression was associated with borrowing used
      injecting equipment. IDU who reported borrowing injecting equipment between 1980
      and baseline 10-99 times or > 99 times had a RH of 0.44 (95% CI, 0.22-0.88) and
      0.19 (95% CI, 0.03-0.37), respectively, compared with IDU who had borrowed < 10
      times. p24 antigen positivity was more predictive than core antibody negativity
      in a model with time-dependent variables, the relative risk for p24 antigen
      positive participants was 3.5 (95% CI, 1.3-9.3). Additional analysis of
      progression to AIDS in a larger group of IDU showed comparable results with
      regard to the effect of borrowing on progression. CONCLUSIONS: Our observation
      that those IDU who reported borrowing injecting equipment most frequently
      appeared to have the lowest rate of progression, corrected for some sources of
      potential confounding, requires further epidemiologic confirmation and extended
      laboratory studies since other sources of bias might have been present. Baseline
      CD4 count, age and core antibody or p24 antigen were predictive of progression in
      IDU. We wish to emphasize that our results do not imply that borrowing should be
      encouraged, but may have implications for our understanding of HIV pathogenesis.

PMID- 8267911
TI  - Knowledge of HIV serostatus and preventive behaviour among European injecting
      drug users. The European Community Study Group on HIV in Injecting Drug Users.
AB  - OBJECTIVE: To study the effect of knowledge of HIV serostatus on behaviour for
      preventing the acquisition or transmission of HIV among European injecting drug
      users (IDU). METHODS: Data on behaviour and prior knowledge of HIV status were
      gathered during a multicentre cross-sectional survey of 200 European IDU
      recruited in 12 European countries in 1990. The respective proportions of IDU who
      (1) used condoms, (2) did not give their used injecting equipment to other IDU
      and (3) injected drugs safely (ether did not re-use other IDU's equipment or re
      used it only after disinfection with bleach, alcohol or boiling water during the
      6 months preceding interview were compared according to whether they knew their
      HIV serostatus for at least 6 months prior to interview. RESULTS: In comparison
      with IDU who had never been tested, IDU who knew that they were HIV-seropositive
      were more likely to always use condoms [rate ratio (RR) = 3.1; 95% confidence
      interval (CI), 2.3-4.2] and never gave their used equipment to other IDU (RR =
      1.3; 95% CI, 1.2-1.5), but did not differ with regard to safe injecting practices
      (RR = 1.0; 95% CI, 0.9-1.1). Compared with IDU who had never been tested, IDU
      with a negative test tended to inject drugs safely more often (RR = 1.1; 95% CI,
      1.02-1.2). There was no significant difference in condom use (RR = 0.7; 95% CI,
      0.5-1.1). CONCLUSION: These results indicate that the knowledge of HIV serostatus
      may help to reduce HIV transmission from HIV-positive IDU to others through safer
      injecting and sexual behaviour. However, for HIV-negative IDU safer injecting
      behaviour appears to be better accepted than safer sexual behaviour.

PMID- 8267912
TI  - The assumption of no long reporting delays may result in underestimates of US
      AIDS incidence.
AB  - OBJECTIVE: To evaluate the effect of the assumption of no long reporting delays
      on estimates of AIDS incidence. DESIGN: Reported AIDS cases must be adjusted for
      reporting delays to estimate AIDS incidence. We compared the adjustments supplied
      with the Centers for Disease Control and Prevention (CDC) AIDS Public Information
      Data Set with a set of adjustments that differ with respect to CDC assumption of
      no long delays. Both methods assume that no changes in delay have occurred
      throughout the reporting period. METHODS: Probability distributions of reporting
      delays were calculated from the delay adjustment weights supplied by CDC, and
      from an alternative method that estimates the probability of long delays from the
      surveillance data. AIDS incidence estimates from these two approaches were
      calculated and compared. RESULTS: The CDC adjustments assume that there will be
      no reporting delays longer than 61 months, whereas the alternative method
      estimates that 5.9% of case reports will be delayed longer than 61 months. The
      CDC adjustments result in lower estimates of AIDS incidence and a flattening of
      the epidemic. CONCLUSIONS: In addition to a 6.2% reduction in total estimated
      AIDS incidence, the CDC assumption changes the shape of the estimated epidemic.
      These may result in as much as 4-21% reductions in model estimates of HIV
      incidence and prevalence.

PMID- 8267913
TI  - Transmission of HIV by blood screened as negative for HIV antibodies.

PMID- 8267914
TI  - Transfusion-related AIDS and HIV infection in Belgium.

PMID- 8267915
TI  - T-helper cross reactivity to viral recombinant proteins in HIV-2-infected
      patients.

PMID- 8267917
TI  - Voluntary confidential HIV testing for couples in Kigali, Rwanda.

PMID- 8267916
TI  - Sensitivity and specificity of complexed p24 antigen assay for early diagnosis of
      perinatal HIV-1 infection.

PMID- 8267918
TI  - HTLV-II in African prostitutes from Cameroon.

PMID- 8267919
TI  - Misdiagnosis of HTLV-II infection using HTLV-I screening assays. HTLV-I/II
      Spanish Study Group.

PMID- 8267920
TI  - Impact of the 1993 revision of the CDC case definition on the performance of the
      WHO and PAHO clinical case definitions for AIDS.

PMID- 8267921
TI  - Update on the HIV epidemic in Cameroon.

PMID- 8267922
TI  - An easy and quick method for the diagnosis of visceral leishmaniasis in HIV-1
      infected individuals.

PMID- 8267923
TI  - Turner syndrome patients as adults: a study of their cognitive profile,
      psychosocial functioning and psychopathological findings.
AB  - In this study we collected data on the cognitive abilities, psychosocial
      adjustment and psychopathology of 20 non-institutionalized adult Turner syndrome
      patients. The majority of them had a normal intelligence, most were socially well
      adapted and no high prevalence of psychopathology was noted. In only one patient
      evidence of a serious bipolar hypomanic disorder and antisocial personality was
      found, and in one other an episode of anorexia nervosa. Nevertheless, 50% of the
      women expressed feelings of low self-confidence, depression and social insecurity
      i.e. achieving a mature level of psycho-social functioning remains a problem for
      a number of Turner individuals. In the counseling process of adult Turner
      patients special attention should be given to the social and psychological
      functioning so that intervention can be made if social awkwardness and
      psychological well-being becomes a problem.

PMID- 8267924
TI  - Genetic predisposition and IDDM in Greece.
AB  - Serological typing of HLA-DR antigens was performed on 116 patients with IDDM and
      380 healthy controls. As expected a high incidence of HLA-DR3 and DR4 antigens
      was observed in patients with IDDM. However, the HLA-DR2 antigen, which rarely
      occurs in IDDM and is considered to confer protection against IDDM, was found in
      equal distribution (35%) in both patients and controls. HLA-DQ genotype analysis
      in 10 children with IDDM and 13 controls, all with the HLA-DR2 haplotype, showed
      that the great majority of affected children and normal controls carry the DR2
      (16) or AZH-DQA1 *0102, DQB *0502 subtype. The high incidence of this subtype in
      normal individuals possibly explains why the DR2 antigen does not offer
      protection against IDDM in Greeks.

PMID- 8267925
TI  - TAR syndrome with orofacial clefting.
AB  - A case of TAR syndrome with bilateral cleft lip and palate is presented.
      Bilateral symmetric focomelia, normal thumbs among five fingers of hands,
      synostosis of IVth and Vth metacarpal bones and some defects of lower limbs with
      associated thrombocytopenia were noted. Dysmorphic facial features included
      hypertelorism, epicanthus, blue sclerae, broad nasal root, micrognathia, low-set
      ears, sparse blond hair. To our knowledge this patient represents an unusual
      association of TAR syndrome with orofacial clefting. A common background of TAR
      and Roberts/SC syndrome is suggested.

PMID- 8267926
TI  - Lujan-Fryns syndrome (X-linked mental retardation with marfanoid habitus): report
      of three cases and review.
AB  - We report on three further cases of mildly retarded patients with marfanoid
      habitus and a pattern of minor anomalies. These patients are likely to be
      affected with the Lujan-Fryns syndrome. We have reviewed twenty cases from the
      literature for a better delineation of this newly recognized disorder.

PMID- 8267927
TI  - VACTERL with hydrocephalus. A distinct entity with a variable spectrum of
      multiple congenital anomalies.
AB  - In this report we describe the experience and follow-up data in 4 patients
      presenting the "VACTERL-hydrocephaly association". A review of the literature and
      the present data show that the inheritance pattern of this association is not
      clear at the present time and that data on the long-term prognosis are scarse.

PMID- 8267928
TI  - Neural tube defect and amniotic band sequence.
AB  - A 28-years-old pregnant woman was examined by fetal ultrasonography at 18 weeks'
      gestation. Anencephaly was diagnosed, followed by prostaglandin induced abortion
      and fetotomy. Fetal fragments showed a very small head, bilateral anophthalmy,
      absence of nasal structures and calvarium, intact cranial skin and a very small
      cranial cavity. The right lower limb was reduced to a few toes covered by a large
      amniotic adhesion. The left lower limb showed an amniotic band from sole to
      thigh. The abdominal wall was absent. The diagnoses were amniotic adhesion
      syndrome and cephalic pole induction failure. The pathogenesis of these defects
      has been the subject of controversy. Vascular disruption and secondary reduction
      of the paraaxial mesodermal cells can explain the anomalies observed in this
      case.

PMID- 8267929
TI  - Radiohumeral synostosis, femoral bowing, other skeletal anomalies and anal
      atresia, a variant example of Antley-Bixler syndrome?
AB  - We report a newborn with radiohumeral synostosis, femoral bowing, anal atresia, a
      prominent nose (pear shaped nose), slender ribs, long tapering fingers with
      distal camptodactyly, genital hypoplasia and a neonatal humeral fracture. Among
      the possible differential diagnoses a variant example of Antley-Bixler syndrome
      is considered to be the most likely final diagnosis.

PMID- 8267930
TI  - Duplication in the long arm of the X-chromosome associated with spastic
      paraparesis and premature menopause.
AB  - In this report we describe a 24-year-old mentally normal female with spastic
      paraparesis, premature menopause and with a duplication of Xq22.3-->q27.3. The
      relationship between the X-chromosomal anomaly and the gonadal and neurological
      symptoms is discussed.

PMID- 8267931
TI  - The characteristic phenotype of distal 9q3 trisomy is due to duplication of band
      9q32.
AB  - In this report we describe a 6-month-old female child with inverted duplication
      of bands 9q32-9q33. The phenotypic findings are identical to the clinical
      syndrome previously reported to be associated with 9q31-9q32 duplication. The
      findings in the present child indicate that the minimal segment of overlap in
      this partial trisomy syndrome is 9q32.

PMID- 8267932
TI  - Yq deletions and AZF locus: molecular analysis in two fetuses with non familial
      homogeneous Yq rearrangements.
AB  - Cytogenetic and molecular analyses were carried out in two fetuses with de novo
      non mosaic dic (Y)(q11.2) and Yqsat. Molecular deletion of the region to which
      the AZF locus has been assigned was found in the first case.

PMID- 8267933
TI  - Pure trisomy 17q from a 17;21 translocation.
AB  - We present a female patient with a trisomy 17q23-->qter whose clinical picture
      clearly illustrates the pure trisomy 17q syndrome.

PMID- 8267934
TI  - Congenital hemihypertrophy.
AB  - We present an isolated complete left hemihypertrophy in a girl with follow-up
      data from birth up to the age of 5 months.

PMID- 8267935
TI  - Progressive anterior vertebral body fusion, overgrowth and distinct craniofacial
      appearance.
AB  - In this report we describe the association of progressive anterior vertebral body
      fusion, generalized over-growth especially with large hands and feet and unusual
      thick skin and subcutaneous tissue of upper and lower limbs, and peculiar
      craniofacial appearance.

PMID- 8267936
TI  - Comparison of left ventricular mass and geometry in black and white patients with
      essential hypertension.
AB  - To assess racial difference in cardiac responses to elevated blood pressure, we
      compared echocardiographic measurements of left ventricular (LV) mass and the
      wall thickness to chamber dimension ratio (relative wall thickness) in 380 white
      and 47 black patients with uncomplicated essential hypertension consecutively
      enrolled in echocardiographic research studies at The New York Hospital
      Hypertension Center. Diastolic blood pressure and weight were slightly greater in
      black as compared with white subjects (104 +/- 18 v 98 +/- 11 mm Hg; P = .014 and
      82 +/- 17 v 77 +/- 15 kg; P = .037, respectively), however the groups were
      similar with respect to age, duration of hypertension, cholesterol level,
      cigarette smoking, past use of antihypertensive therapy, family history of heart
      disease, and height. On average, LV mass indexed for body surface area and
      relative wall thickness were significantly greater in blacks than whites (119 v
      105 g/m2; P = .02 and 0.46 v 0.39; P = .003) and blacks had twice the prevalence
      of LV hypertrophy (41% v 19%; P < .001) or concentric remodeling (21% v 12%; P <
      .05). The magnitude of increased LV mass and relative wall thickness in blacks
      was similar in men (132 v 110 g/m2; P = .01 and 0.44 v 0.39; P = .04) and in
      women (107 v 94 g/m2; P = .11 and 0.48 v 0.39; P = .02). In multivariate
      analyses, systolic blood pressure, age, and race were consistently predictors of
      increased LV mass and abnormal cardiac geometry. Cholesterol level was not
      independently associated with increased LV mass but was weakly associated with
      increased relative wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267937
TI  - Hemodynamic reactivity factors to cold pressor test in blacks with sustained
      essential hypertension.
AB  - To evaluate factors that might influence arterial pressure response to stress, 29
      black African subjects were submitted to a cold pressor test. Eleven of them were
      normotensive healthy subjects, and 18 were hypertensive patients (WHO stage I to
      II). Both groups were matched in age (41 +/- 3 years and 42 +/- 3 years,
      respectively) and body mass index (25 +/- 2.10(-4) kg/cm2). After the cold
      pressor test, both groups showed a significant increase in arterial pressure, but
      not in heart rate absolute value. Considering the level of change in each
      parameter, only systolic and pulse pressure showed significant increases in
      hypertensive patients (respectively 16 +/- 5 mm Hg v 22 +/- 3 mm Hg, P < .02 and
      3 +/- 1 mm Hg v 8 +/- 2 mm Hg, P < .01). An inverse relationship was shown in
      both study populations: change in systolic arterial pressure was positively and
      significantly correlated to the change in heart rate (r = +0.63, P < .02), but
      not to the change in pulse pressure (r = 0.34, P = NS) in normotensive subjects.
      Inversely, in hypertensive patients there was a positive and significant
      correlation with the change in pulse pressure (r = +0.52, P < .01), but not with
      the change in heart rate. We conclude that arterial pressure reactivity to the
      cold pressor test might be influenced by different mechanisms in normotensives
      and hypertensives. In the former, the withdrawal of parasympathetic tone might be
      the main factor, whereas in hypertensives, the cushioning of function of large
      arteries might be the principal factor.

PMID- 8267939
TI  - Cardiovascular effects of long-term endothelin infusion and responses to
      endothelin during ACTH infusion in conscious sheep.
AB  - Infusion of endothelin-1 (ET-1) (2000 pmol/h) into conscious sheep for 6 days
      caused a sustained increase in mean arterial pressure (MAP) of 19 +/- 1 mm Hg.
      This response was mediated by the vasoconstrictor effect of ET-1 and was
      accompanied by a fall in cardiac output. Plasma renin concentration fell
      throughout the infusion and atrial natriuretic peptide was increased on day 1 of
      ET-1 infusion. Hematocrit dramatically increased, probably mainly due to plasma
      loss resulting from the ET-1-induced increased capillary hydrostatic pressure. To
      determine whether increased pressor responsiveness to ET-1 played a role in the
      rise in MAP caused by corticotropin (ACTH), the responses to bolus doses of ET-1
      were evaluated before ACTH and on days 3 and 5 of ACTH infusion (5
      micrograms/kg/day). ACTH increased MAP from 71 +/- 2 to 87 +/- 3 mm Hg. On the
      control day ET-1 (400, 1200, and 2000 pmol) increased MAP by 5 +/- 1, 18 +/- 6
      and 35 +/- 11 mm Hg, respectively. No initial vasodilation occurred. The
      responses to all doses of ET-1 were similar during ACTH infusion. Plasma levels
      of ET-1 did not increase during ACTH infusion. These results demonstrate that
      long-term infusion of ET-1 caused a sustained increase in blood pressure. There
      was no evidence that the sensitivity or responsiveness to ET-1 were altered
      during infusion of ACTH. In conclusion, ET-1 could play a role in the
      pathogenesis of hypertension but does not appear to be involved in the increase
      in blood pressure caused by ACTH.

PMID- 8267938
TI  - Nature of elevated blood pressure in normoalbuminuric type I diabetic patients.
      Essential hypertension?
AB  - This study was undertaken to characterize type I diabetic patients with essential
      hypertension with respect to kidney function, renal hormones, and endothelial
      function. After 4 weeks without antihypertensive treatment, a cross-sectional
      study was carried out in the following groups: group 1, 14 healthy controls;
      group 2, 13 nondiabetic patients with essential hypertension (blood pressure > or
      = 140/90 mm Hg); group 3, 11 type I diabetic patients with hypertension but
      urinary albumin excretion (UAE) persistently normal (UAE: 10 mg/24 h, range 3 to
      18) both before, during, and after discontinuing antihypertensive treatment;
      group 4, 15 type I diabetic patients with clinical nephropathy (UAE: 611 mg/24 h,
      range 192 to 3837) and hypertension. Systolic and diastolic blood pressures were
      similar in the three hypertensive groups: 147/96 +/- 8/6, 150/94 +/- 11/9, and
      152/92 +/- 12/6 mm Hg (groups 2, 3, and 4, respectively) but elevated compared
      with controls (114/74 +/- 9/9 mm Hg, P < .001). The diabetic patients with
      essential hypertension were hyperfiltering in contrast to patients with
      nephropathy (glomerular filtration rate 114 +/- 23 v 90 +/- 21 mL/min/173 m2, P <
      .05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267940
TI  - Plasma norepinephrine changes after arousal and exercise were enhanced in
      conscious pigs with perinephritic hypertension.
AB  - This study found that pigs in the early stages of perinephritic hypertension had
      enhanced plasma norepinephrine (NE) and heart rate (HR) responses to behaviorally
      arousing stimuli (lifting in a canvas sling) and exercise. In the hypertensive
      animals, the increase in plasma NE in response to behavioral arousal caused by
      lifting was double that of the intact group, and the HR response was 50% greater.
      The increase in plasma NE in response to exercise was six times greater in
      hypertensive pigs. By contrast, mean arterial pressure changes were not enhanced
      in the hypertensive group. Exaggerated catecholamine responses in plasma to
      lifting and exercise stimulation were present when hemodynamic responses were not
      exaggerated.

PMID- 8267941
TI  - Altered local regulation of blood flow and shear rate in renal hypertension.
AB  - The purpose of this study was to evaluate acute and chronic autoregulation of
      blood flow in the cremaster muscle of one-kidney, one-clip (1K1C) hypertensive
      rats and to investigate alterations of shear stress during the development of
      hypertension. Unilateral renal artery stenosis and contralateral nephrectomy were
      performed in half of the rats and a sham operation was carried out in the other
      half. Mean blood pressure was significantly increased at 1 (38%) and 4 (34%)
      weeks in 1K1C rats v age-matched controls. Heart rate was significantly increased
      15% at 1 week in 1K1C rats but returned to the control level at 4 weeks.
      Cremaster arteriolar dimensions were measured in vivo by intravital microscopy.
      Resting diameter of the first-order arteriole (1A) in 1K1C rats was decreased by
      25% (P < .05) at 1 week and by 16% at 4 weeks (ns). Measured by the dual-slit
      technique, total blood flow to the cremaster muscle in 1K1C rats was reduced by
      58% (P < .05) at 1 week but was not significantly different from control at 4
      weeks. Wall shear rate calculated in the 1A of 1K1C rats was not significantly
      different from control at 1 week but was elevated 70% (P < .05) at 4 weeks.
      Therefore, autoregulation of blood flow in skeletal muscle is impaired and/or
      overridden in the acute phase of 1K1C hypertension. Shear rate, however, did not
      deviate from the control level until later, which might be the result of impaired
      function of the endothelium in chronic hypertension.

PMID- 8267942
TI  - Stimulation of renal interstitial bradykinin by sodium depletion.
AB  - The ability to measure and detect change in renal bradykinin in situ would allow
      study of relations between local kinin production and renal function in
      hypertensive or diabetic disorders. A new renal interstitial microdialysis
      technique allowed collections of renal subcapsular interstitial fluid 2 weeks
      after microdialysis probe placement in conscious dogs (n = 5) on a normal sodium
      diet (50 mEq/day) and for 5 subsequent days on low sodium intake (10 mEq/day).
      Although interstitial bradykinin measured by radioimmunoassay (RIA) was
      undetectable (< 0.08 pg/min) during normal sodium intake, it was detectable (0.34
      +/- 0.02 pg/min) after 1 day of low sodium. The kinin level at the end of the 5
      subsequent days on low sodium was 1.94 +/- 0.09 pg/min (P < .01). The data show
      that renal interstitial kinin can be measured in situ. Further, a low sodium diet
      can rapidly increase interstitial kinin in the conscious dog.

PMID- 8267943
TI  - Rare renal transcription of the atrial natriuretic factor gene in rats.
      Demonstration by polymerase chain reaction.
AB  - Renal synthesis of a peptide homologous to atrial natriuretic factor (ANF) has
      been demonstrated. The aim of the present study was to determine if transcription
      of the ANF gene occurs in the kidney. Rat renal RNA was extracted from whole
      kidneys, and, separately, from the cortex and outer and inner medulla of rat
      kidneys. Probing with rat ANF-cDNA did not reveal a detectable message in
      Northern blot analysis, even when large quantities of RNA were used at low
      stringency hybridization conditions. Therefore, reverse transcription (RT)
      followed by 35 cycles of polymerase chain reaction (PCR) was used to search for
      the renal message for ANF. Two 21-mer primers encompassing the 450 base pairs
      (bp) of the coding region of the gene were used. Each cycle consisted of
      annealing at 56 degrees C, extension at 72 degrees C, and denaturation at 94
      degrees C. The PCR product was proven to be identical to the ANF gene by high
      stringency hybridization, which revealed the expected 450-bp hybrid band.
      Furthermore, the sequence of this product was identical to that of the coding
      region of the ANF gene. We used an RNA-specific PCR to obtain this band as a
      single reaction product. We conclude that the transcript of the ANF gene exists
      in the kidney, at extremely low levels. The low abundance of the RNA message
      raises major concerns about its physiologic relevance. Direct evidence for the
      translation of this transcript, and its quantification and localization, is still
      required to determine its significance.

PMID- 8267944
TI  - Accuracy and reproducibility of 30 devices for self-measurement of arterial blood
      pressure.
AB  - Thirty commercially available noninvasive devices for self-measurement of blood
      pressure were tested for accuracy and reproducibility against intraarterial
      measurement in 15 normotensive and 15 hypertensive subjects. For reference to
      outpatient measurements, a standard sphygmomanometer was included. Analysis of
      the data for any device was performed according to a statistical model in which
      two types of errors, representing accuracy and reproducibility, were
      distinguished: offset (mean difference between intraarterial measurement and
      device) and standard deviation (comprising intraindividual and interindividual
      variability). Linearity of the devices was analyzed by linear regression with
      intraarterial measurement as independent variable. The average offset of all
      tested devices amounted to 11.7 mm Hg (ranging from -0.2 to 21.4 between
      instruments) for systolic blood pressure and -1.6 mm Hg (range -11.4 to 8.1) for
      diastolic blood pressure. The standard deviation between instruments ranged from
      7.0 to 15.4 mm Hg for systolic and from 3.3 to 16.0 mm Hg for diastolic blood
      pressure. Except for the devices based on the oscillometric principle, most (semi
      ) automated devices demonstrated a variability similar to the mercury
      sphygmomanometer (offset = 14.3 for systolic and 0.1 mm Hg for diastolic
      pressure; standard deviation = 7.5 for systolic and 5.6 mm Hg for diastolic blood
      pressure). Devices based on the oscillometric principle had a significantly
      larger variability. It is concluded that new devices should be tested for
      accuracy and reproducibility before application for clinical use. Blood pressure
      measurements from instruments with larger offset are only comparable to values
      from other instruments after rescaling in accordance with their offset.

PMID- 8267945
TI  - Ambulatory monitoring of blood pressure in normal pregnancy.
AB  - The definition of hypertensive disorders in pregnancy is plagued by many
      difficulties, in part related to the limits of intermittent clinic readings of
      blood pressure. In order to better define the evolution of arterial blood
      pressure in normal subjects during normal pregnancy, casual and ambulatory
      (Spacelabs 90207, n = 22 or Diasys 200, n = 26) measurements of blood pressure
      were performed at gestational months 3, 6, and 9, in 48 normal women aged 18 to
      39, both nulliparas (n = 19) and multiparas (n = 29). Ambulatory blood pressure
      levels were lowest in the first gestational trimester (24-hour mean: 104 +/- 8/63
      +/- 6 mm Hg) and rose by a small increment during the last trimester (109 +/-
      8/67 +/- 7 mm Hg at 8 months). Mean daytime ambulatory pressure was almost
      superimposable to clinic measurements at the three time points. A day-night
      variation in blood pressure level was detectable in all subjects at each
      recording. It is concluded that during normal pregnancy, ambulatory blood
      pressure levels were highest in the day and lowest at night at all gestational
      ages and increased only minimally before the ninth month. Reference values, as
      defined by the percentile distribution of daytime and nighttime systolic and
      diastolic blood pressure, may help define more precisely an alteration in the
      level and/or the circadian variation of arterial blood pressure during abnormal
      pregnancies.

PMID- 8267946
TI  - HLA antigens in borderline and essential hypertension.
AB  - The subject of investigation was the comparison of HLA antigen distribution in
      people with borderline hypertension (BH) and essential hypertension (EH). One
      hundred twenty-one men with BH and 60 men with EH were studied. The HLA frequency
      was compared with that in 858 healthy men, who were blood donors. In BH the
      increase of B16, B18, and Cw4 and the decrease of A11 and B5 antigen frequency
      were found. In comparison with St. Petersburg's healthy population, patients with
      EH were characterized by increasing antigens B18, B41, Cw2, and Cw4 frequency.
      The coincidence of increased antigen B18 and Cw4 representation in BH and EH
      allows us to consider them to be immunogenetic markers or predictors of
      development of EH.

PMID- 8267947
TI  - The effect of blood pressure cuff inflation on sleep. A polysomnographic
      examination.
AB  - Ambulatory blood pressure monitors are being used increasingly to define blood
      pressure in contexts other than the doctor's office. With increasing interest in
      both effects of treatment on quality of life and chronobiology of hemodynamic
      regulation, such monitors have also been used to define blood pressure during
      sleep. Unfortunately, few investigators have scrutinized the effect of such
      recordings on sleep, as defined precisely with polysomnography. We studied a
      diverse group of 12 unmedicated individuals, measuring BP by cuff inflation every
      60 min. The polysomnogram was then analyzed for periods of wakefulness and
      arousals from sleep. Cuff inflation was associated with increased arousals (P <
      .0001) and wakefulness (P < .0001). In addition, subjects recalled 58% of the
      cuff inflations. Effects of cuff inflation on a second night of recording
      indicated some habituation. Nocturnal BPs measured by such techniques are still
      valuable, but one must have some reservations that these measures accurately
      reflect BP during sleep.

PMID- 8267948
TI  - Low-dose angiotensin II increases glucose disposal rate during euglycemic
      hyperinsulinemia.
AB  - To study the metabolic effects of angiotensin II we examined the glucose disposal
      rate and calf blood flow in healthy men (n = 39) during euglycemic
      hyperinsulinemia followed by a period with simultaneous angiotensin II infusion
      at a low dose (0.1 ng/kg/min). Angiotensin II infusion abruptly increased the
      glucose disposal rate significantly as compared with glucose disposal rate during
      euglycemic hyperinsulinemia only. There were no differences in blood glucose or
      plasma insulin between the euglycemic hyperinsulinemic and the angiotensin II
      infusion period. During hyperinsulinemia alone, blood pressure was unchanged
      while calf muscle blood flow increased significantly as compared with the
      baseline period, while during the angiotensin infusion the systolic blood
      pressure increased and calf blood flow decreased significantly as compared with
      the hyperinsulinemic period. We conclude that angiotensin II within physiological
      range stimulates insulin-mediated glucose uptake in healthy men. The mechanisms
      are, however, unclear, but changes in blood flow are probably not responsible for
      the observed effects.

PMID- 8267949
TI  - A review of the Joint National Committee on Detection, Evaluation, and Treatment
      of High Blood Pressure. The Fifth Report, 1993.
AB  - JNC-V is a comprehensive document that also contains a variety of specific
      information about drug actions, interactions, and specific indications and
      contraindications for each class of antihypertensive drugs. In addition, there
      are recommendations regarding patient evaluation and follow-up. Individual
      sections deal with blood pressure management in special situations and in
      different populations. References are included to support the assertions made and
      to permit further assessment by the reader of some of the evidence that the
      committee used to reach its conclusions. In sum, the new Joint National Committee
      Report continues a tradition of bringing to the profession and the public at
      large the current best judgment regarding practice that is constantly in
      evolution. It is not the ultimate document, but another step toward a goal that
      remains the same. That goal is to reduce cardiovascular morbidity and mortality,
      improve and extend life, and to achieve these objectives in the least intrusive
      and most efficient way possible.

PMID- 8267950
TI  - The molecular biology of tick-borne encephalitis virus. Review article.
AB  - Tick-borne encephalitis (TBE) virus is a member of the flavivirus genus and the
      family Flaviviridae. Like other flaviviruses such as yellow fever, Japanese
      encephalitis or the dengue viruses, it is an important human pathogen, endemic in
      many European countries, Russia and China. The disease can be effectively
      prevented by vaccination with a formalin-inactivated whole virus vaccine. In
      recent years major advances have been made in the understanding of the molecular
      biology of TBE virus, including the complete sequence analysis of the genomic RNA
      of the European and Far Eastern strains. As shown in these studies, the virion
      RNA contains a single long open reading frame that codes for the structural
      proteins at the 5' end and the nonstructural proteins at the 3' end. Co- and
      posttranslational cleavages by a viral and cellular proteases lead to the
      formation of individual viral proteins. The mature virion is composed of an
      isometric capsid surrounded by a lipid envelope with two membrane-associated
      proteins. One of these, protein E, is of paramount importance for several
      important viral functions, especially during the entry phase of the viral life
      cycle. Protein E is also responsible for the induction of a protective immune
      response. A detailed map of antigenic sites has been established and the
      structure of an anchor-free form of E is currently being investigated by X-ray
      diffraction analysis. Understanding the molecular basis of the functions of this
      protein together with the knowledge of its three-dimensional structure may
      provide clues for developing specific antiviral agents. Protein E has also been
      shown to be an important determinant of virulence, with single amino acid
      substitutions at selected sites leading to attenuation. Engineering of such
      mutations into cDNA clones to produce new recombinant viruses may open up new
      avenues for the development of live vaccines.

PMID- 8267951
TI  - Crossed immunoelectrophoresis used for bacteriological diagnosis in patients with
      endocarditis.
AB  - Sera from 151 patients suspected of having endocarditis were obtained during a
      period of 3 1/2 years at Rigshospitalet, Copenhagen. The sera were examined by
      crossed immunoelectrophoresis for antibodies to bacteria causing endocarditis.
      The patients were divided into four groups: 1. Patients with definite
      endocarditis, 2. Patients with culture-negative endocarditis, 3. Patients with
      uncertain endocarditis, and 4. Patients without endocarditis. In sera from
      patients suffering from endocarditis caused by viridans streptococci,
      precipitating antibodies were demonstrated by crossed immunoelectrophoresis
      (diagnostic specificity = 86%; diagnostic sensitivity = 100%) while other
      bacterial etiologies of endocarditis were less reliably demonstrated by this
      method.

PMID- 8267952
TI  - Comparative study of the cellular fatty acids of methicillin-resistant and 
      susceptible Staphylococcus aureus.
AB  - The cellular fatty acid compositions of 26 strains of methicillin-resistant
      Staphylococcus aureus (MRSA) and 17 strains of methicillin-susceptible S. aureus
      (MSSA) were analyzed by gas-liquid chromatography. The fatty acid compositions of
      the two groups were very similar with 16 identified components. The major fatty
      acids were Ci14 = 0, Ci15 = 0, C18 = 0 and C20 = 0. Among these fatty acids, the
      percentage of the Ci15 = 0 fatty acid component of MRSA strains (11.4 +/- 3.9%)
      was statistically higher than that of MSSA strains (6.2 +/- 2.4%) (p < 0.001). On
      the other hand, the percentage of the C20 = 0 fatty acid components of MRSA
      strains (20.2 +/- 8.8%) was statistically lower than that of MSSA strains (30.7
      +/- 10.4%) (p < 0.001). The production of beta-lactamase and beta-hemolysin in
      both groups' strain was also unrelated to the relative amounts of the fatty acid
      components. These results indicated a statistical tendency for the percentage
      fatty acid compositions of the MRSA strains to be quantitatively different from
      those of the MSSA for both the Ci15 = 0 and C20 = 0 fatty acid components.
      Analysis of the fatty acid compositions may have an application in the
      differentiation of MRSA and MSSA strains.

PMID- 8267953
TI  - Generation of reactive oxygen species by blood monocytes during acute Plasmodium
      knowlesi infection in rhesus monkeys.
AB  - The status and kinetics of monocyte activation during acute P. knowlesi infection
      was investigated by latex-induced, luminol-dependent chemiluminescence (CL)
      response. The contribution of various reactive oxygen species (ROS) to CL
      response was estimated before infection and at peak parasitaemia (day 7 post
      infection) by using scavengers of ROS (benzoate, catalase and superoxide
      dismutase). The chemiluminescence index (CLI) was not found to be significantly
      different from controls on day 2 postinfection, but was significantly higher on
      days 5 and 7 postinfection. Hydroxyl radical (OH.) production was considerably
      elevated, whereas superoxide anion (O2-.) and hydrogen peroxide (H2O2) production
      dropped following infection. These changes in generation of ROS are discussed in
      relation to the progression of parasitaemia to high levels, immunopathology and
      immunosuppression during acute P. knowlesi infection.

PMID- 8267954
TI  - Neuronal uptake of plasma proteins after transient cerebral ischemia/hypoxia.
      Immunohistochemical studies on experimental animals and human brains.
AB  - Rapid uptake of plasma proteins into damaged neurons has been demonstrated
      previously after lesions which cause early breakdown of the blood-brain barrier
      (BBB). The present study was undertaken to see whether a similar uptake occurred
      after hypoxic/ischemic episodes in men and experimental animals. Forebrain
      ischemia was produced in rats by a combination of carotid clamping and
      hypotension for 15 min, followed by recirculation for 6 h, 24 h, 48 h and 5 d.
      Paraffin sections from the brains were incubated with antiserum against albumin,
      and parallel sections were stained with hematoxylin and eosin (H & E). Breakdown
      of the BBB with extravasation of albumin was seen after 6 h in the lateral
      reticular nucleus of the thalamus, the dorsolateral striatum, and in restricted
      areas of the cerebral cortex. Uptake of albumin into damaged neurons was seen in
      the same structures, and partly before reliable changes were observed in
      routinely stained sections. With longer survival periods, the staining of the
      neuropil became stronger and more neurons in the damaged areas were positively
      labeled. After 48 h and 5 d many neurons in the hippocampal sector CA1 had also
      taken up plasma proteins. A similar uptake of plasma proteins into damaged
      neurons was seen in brains from patients with histological evidence of hypoxic
      injury. Even the small leakage of proteins that occurs after hypoxic/ischemic
      lesions is thus sufficient to give a definite immunostaining of damaged neurons.

PMID- 8267955
TI  - Direct estimation of volumes in ovarian follicles using the nucleator.
AB  - The aim of the study was to evaluate the precision of the nucleator principle
      with regard to estimation of follicle, oocyte and antral volumes in individual
      follicles, as well as their average volumes in a group of follicles. Nine
      isolated murine ovarian follicles embedded in plastic were orientated
      isotropically, cut into 20 microns serial sections, and stained with hematoxylin.
      In each follicle the volumes of the follicle, the antrum and the oocyte were
      estimated in two ways, both unbiased: Firstly, in just one unique section through
      the follicle, viz. the section which contains the unique sampling point--the
      nucleolus of the oocyte--using the nucleator principle, and, secondly, in the
      complete set of follicle sections using the Cavalieri principle. Estimates using
      the Cavalieri, which are very precise (CEFollicle approximately 0.03, CEOocyte
      approximately 0.11, CEAntrum approximately 0.16), were interpreted as the "true"
      values. Therefore, the precision (estimator variation) of the nucleator estimates
      could be calculated. The nucleator estimates correlated well with the Cavalieri
      estimates: r(follicle) = 0.95; r(antrum) = 0.88; r(oocyte) = 0.83. The nucleator
      provides very precise estimates of the volumes of follicle, oocyte and antrum
      with a minimal amount of effort, since the estimates are derived from
      measurements in only four directions sampled in a uniform systematic way, the
      first direction being chosen at random, in only one section through the follicle.
      Moreover, it is not necessary to know the precise thickness of the section, and
      finally, the estimates are expressed in correctly dimensioned terms. The
      estimator variation of the nucleator (CE = 0.28) is of minor importance compared
      to the biological variation (CV = 0.47) in this realistic sample of follicles.

PMID- 8267956
TI  - ABH secretor status, as judged by the Lewis phenotypes, in Norwegian survivors
      from meningococcal disease.
AB  - Survivors from meningococcal disease (serogroups B and C) and a control series
      (blood donors) were examined for their ability to secrete ABH blood group
      substance. The examination was done indirectly by determining their Lewis
      phenotypes. There was no significant difference in the secretor status between
      the two groups.

PMID- 8267958
TI  - Staphylococcus lugdunensis: an important cause of endocarditis. A case report.
AB  - Staphylococcus lugdunensis endocarditis was diagnosed in a 55-year-old woman
      maintained on chronic haemodialysis. S. lugdunensis was isolated from blood and a
      Gore-Tex graft fistula at admission, and vegetations with Gram-positive cocci
      were found on the mitral cusps at autopsy.

PMID- 8267957
TI  - Evaluation of eight commercial kits for Helicobacter pylori IgG antibody
      detection.
AB  - Eight commercial kits and an in-house ELISA for detection of IgG antibodies
      against Helicobacter pylori were evaluated for their use in diagnosis of H.
      pylori infection and in epidemiological research: Helico-GTM (Porton-Cambridge),
      G. A. P. test (Bio-Rad), H. pylori antibodies ELISA (Biometra), Anti-H. pylori
      IgG EIA (Roche), 2nd generation H. pylori EIA (Roche), Anti-H. pylori MTP-assay
      (Roche), Pylori stat test kit (Whittaker), Pyloriset latex agglutination kit
      (Orion), and the in-house ELISA based on heat-stable antigens. Fifty-four
      patients with dyspepsia (31 H. pylori positive by culture or microscopy) and 68
      asymptomatic persons were tested. Sensitivities for the eight kits were 71%, 77%,
      90%, 84%, 87%, 94%, 90%, 87%, and 87%, specificities were 74%, 65%, 74%, 74%,
      83%, 83%, 70%, 65%, and 65%, respectively. For epidemiological use the estimated
      seroprevalence varied within approximately 15% in all age groups. Sensitivities
      and specificities obtained in different studies reveal as great differences in
      the results with the same kit as between results obtained with different kits in
      the same study. Kits with the highest sensitivities tend to be the same in all
      studies. It is therefore more important to test a kit in the population to which
      it is to be applied than to choose a specific kit.

PMID- 8267959
TI  - Branhamella catarrhalis pathogenesis in SCID and SCID/beige mice. Brief report.
AB  - SCID and SCID/beige mice were used to study the pathogenesis of B. catarrhalis
      administered by intranasal, intraperitoneal or intravenous routes. Challenged
      adult animals did not appear overtly clinically ill. Similar symptoms were
      observed regardless of the challenge route, and pretreatment of mice with human
      transferrin did not enhance clinical virulence. Susceptibility to B. catarrhalis
      appeared to be age-dependent as some mice under one week of age died following
      challenge. Postmortem findings included circumscribed pale foci on the liver,
      splenomegaly and mineralization of the myocardium. Presence of lesions did not
      correlate with the assessment of clinical well being, and severity of the lesions
      was found to be challenge strain-dependent. Liver lesions and splenomegaly were
      not observed in animals challenged with heat-killed bacteria or placebo.
      SCID/beige mice were more affected than SCID mice both clinically and
      pathologically, suggesting that natural killer cell and polymorphonuclear cell
      functions may be important in resolving B. catarrhalis challenge.

PMID- 8267960
TI  - Flow cytometric DNA analysis of adenocarcinomas of the vermiform appendix. Brief
      report.
AB  - The DNA ploidy status and S-phase fraction of eight adenocarcinomas of the
      vermiform appendix diagnosed in Iceland during 1974-1990 were analyzed by flow
      cytometry. Four cases were classified as Dukes' stage B2 and four cases as Dukes'
      stage D. Seven tumors were diploid and one was aneuploid. The DNA aneuploid tumor
      was the only one which metastasized outside the abdominal cavity. The S-phase
      fraction in general was low. The results of this study do not indicate any
      significant correlation between ploidy status and clinical behavior.

PMID- 8267961
TI  - Comparison of expression of a series of mammalian vector promoters in the
      neuronal cell lines PC12 and HT4.

PMID- 8267962
TI  - Adsorption of glycosphingolipids onto latex (polystyrene) beads.

PMID- 8267963
TI  - A quantitative method for assessing protein abundance using enhanced
      chemiluminescence.

PMID- 8267964
TI  - Co-localization of molecular mass marker proteins on western blots.

PMID- 8267965
TI  - Efficient extraction of viral RNA for PCR amplification.

PMID- 8267966
TI  - Swift identification of recombinant proteins from lambda-phage libraries without
      resorting to liquid cultures or lysogens.

PMID- 8267967
TI  - Two-stage ligation-mediated PCR enhances the detection of integrated transgenic
      DNA.

PMID- 8267968
TI  - The use of PCR to recover genes cloned in stringent plasmids from nonviable
      bacterial colonies.

PMID- 8267969
TI  - Identifying false positives during the first round of cDNA library screening.

PMID- 8267970
TI  - A convenient and efficient method for growing and short-term storage of miniprep
      bacterial cultures.

PMID- 8267971
TI  - A rapid procedure for microextraction of genomic DNA from whole blood for
      clinical diagnostic tests.

PMID- 8267972
TI  - Stabilization of nucleic acids in whole blood: an alternative to Guthrie cards.

PMID- 8267973
TI  - A procedure to determine gene intron-exon boundaries directly from phage and
      cosmid clones.

PMID- 8267974
TI  - Small broad-host-range gentamycin resistance gene cassettes for site-specific
      insertion and deletion mutagenesis.

PMID- 8267975
TI  - In-gel hybridization to separated yeast chromosomes.

PMID- 8267977
TI  - An inexpensive method that prevents microcentrifuge tubes from popping.

PMID- 8267976
TI  - DNA sequencing artifacts: band smearing and loss.

PMID- 8267978
TI  - Gel compressions and artifact banding can be resolved in the same DNA sequence
      reaction.

PMID- 8267979
TI  - An easily synthesized, photolyzable luciferase substrate for in vivo luciferase
      activity measurement.
AB  - Many reporter gene assays require killing the cell by fixation or lysis. For
      assays in living cells, the substrate delivery is inefficient and cannot be
      supplied in situ in a bolus, which makes assays highly variable. We report a
      simple synthesis of a luciferin ester that is both photolyzable and cleaved by
      endogenous esterases such that luciferase activity in living cells is easily
      monitored. Although the photolyzed substrate can be delivered in bolus, the rapid
      equilibration of the luciferin ester in the cell and the continuous delivery by
      the endogenous esterases allow stable, long-term measurements of luciferase
      activity.

PMID- 8267980
TI  - A simple method for genetic typing of transferrins in nonhuman primates.
AB  - The serum protein transferrin (Tf) is a valuable marker for genetic studies of
      primates, because it is usually polymorphic, exhibiting as many as 13 allelic
      forms with high heterozygosity. The standard procedure to detect the different
      phenotypes requires vertical electrophoresis on polyacrylamide gels for 18 h at 4
      degrees C. We have simplified the procedure by using the automated programmable
      PhastSystem for electrophoresis, which uses precast miniature gels and takes less
      than 2 h. Also, we have developed a pool of sera that displays the 6 most common
      alleles in rhesus monkeys. This pool allows for a more accurate assignment of
      phenotypes. Using this simplified procedure, we have typed over 3000 monkeys of
      various species and have confirmed the reliability of this technique for
      parentage determination.

PMID- 8267981
TI  - Downstream insertion of the adenovirus tripartite leader sequence enhances
      expression in universal eukaryotic vectors.
AB  - A series of universal eukaryotic gene expression vectors was constructed. All
      vectors contain a viral promoter and enhancer, a polylinker for insertion of the
      gene of interest and a polyadenylation sequence. To enhance translation, we
      inserted the tripartite leader sequence of an adenovirus downstream of the
      promoter. Using the chloramphenicol acetyl transferase (cat) gene as a marker, we
      show that the strength of various promoters/enhancers in different cell lines
      differed by two orders of magnitude. The presence of the tripartite leader
      increased the efficiency of gene expression up to 18-fold. The level of increase
      is promoter specific and is most likely influenced by additional sequences
      flanking the tripartite leader sequence.

PMID- 8267982
TI  - Serum-free transfection and selection in Chinese hamster ovary (CHO) cells.
AB  - In this report a method for transfection and selection of mammalian cells in
      serum-free medium is described. Chinese hamster ovary (CHO) cells were grown in
      serum-free medium in plastic dishes coated with one of the following attachment
      factors: poly-D-lysine, Cell-Tak (polyphenolic proteins extracted from the marine
      mussel Mytilus edulis), fibronectin or laminin. Cells grown to 80% confluence
      were transfected with an expression vector encoding the hygromycin resistance
      gene as a selectable marker and beta-galactosidase as the reporter gene.
      Transfectants were selected using hygromycin at a concentration of 500
      micrograms/ml. Both fibronectin and laminin supported colony formation following
      selection in serum-free medium. However, poly-D-lysine and Cell-Tak did not. This
      method can, thus, be used to select for clones producing a recombinant product in
      cells that are growing in serum-free medium from the onset to provide a better
      system from which to purify proteins.

PMID- 8267983
TI  - Generation and identification of recombinant adenovirus by liposome-mediated
      transfection and PCR analysis.
AB  - A simplified method for generating recombinant adenovirus was developed by using
      liposome-mediated co-transfection and by directly observing for the cytopathic
      effect caused by recombinant adenovirus in transfected 293 cells. This approach
      avoided difficulties associated with calcium-phosphate precipitation and agarose
      overlays for plaque assays. The ease of generating recombinant adenovirus was
      considerably improved. Analysis by PCR of DNA samples from the supernatant of the
      cell cultures with the cytopathic effect was also developed, which made
      identification of any newly generated recombinant virus rapid and specific.

PMID- 8267984
TI  - A PCR-based method for site-specific domain replacement that does not require
      restriction recognition sequences.
AB  - We describe a PCR-based method for domain replacement that does not require
      restriction site sequences. We illustrate the technique in which the first
      epidermal growth factor (EGF1)-like domain of factor IX (FIX) is replaced by the
      EGF1-like domain of protein C. The method employs four oligonucleotide primers.
      Two are external primers (forward primer A and inverse primer B) and contain
      sequences flanking the FIX cDNA nucleotides. The other two primers (forward
      primer C and inverse primer D) direct the PCR amplification of the EGF1-like
      domain of protein C, and they are hybrid primers that contain sequences of
      protein C gene at the 3' end and of FIX gene at the 5' end. Thus the amplified
      fragment of EGF1-like domain of protein C (PCEGF1 fragment) is flanked by FIX
      gene sequences on both ends. When this fragment is mixed with FIX cDNA and
      subjected to one cycle of PCR, two products are obtained: one containing PCEGF1
      fragment linked to FIX cDNA sequence upstream and the other containing PCEGF1
      fragment linked to FIX cDNA sequence downstream of its EGF1-like domain. The
      first product is amplified using primers A and D, and the second product is
      amplified using primers B and C. Both products contain overlapping sequences,
      which allow annealing upon mixing. The annealed product is amplified by PCR using
      primers A and B. The final product contains FIX cDNA in which its EGF1 sequence
      has been replaced by the PCEGF1 sequence.

PMID- 8267985
TI  - Anchor-ligated cDNA libraries: a technique for generating a cDNA library for the
      immediate cloning of the 5' ends of mRNAs.
AB  - A new, efficient and simple method based on single-stranded anchor ligation has
      been developed that allows for the generation of an anchor-ligated library from
      which the 5' ends in many mRNAs can be cloned. Random hexamers are used to prime
      poly A+ RNA for the first strand synthesis of a cDNA library, and a modified
      single-stranded anchor is then ligated to the 3' end of the cDNA using T4 RNA
      ligase. The library can then be used to amplify the 5' end of any mRNA expressed
      in the tissue. The efficiency and utility of this method has been demonstrated by
      amplification of three human genes: transferrin receptor, tissue-type plasminogen
      activator and beta actin.

PMID- 8267986
TI  - Electroblotting proteins onto carboxymethylcellulose membranes for sequencing.
AB  - Proteins and peptides separated by polyacrylamide gel electrophoresis either in
      acetic acid-urea or in sodium dodecyl sulfate (SDS)-containing gels were
      electroblotted onto carboxymethylcellulose membrane and eluted from the membrane
      by dilute acid. Polypeptides thus recovered with a high yield can be used to get
      structural or biological data.

PMID- 8267987
TI  - Non-radioisotopic typing of human leukocyte antigen class II genes on
      microplates.
AB  - We describe a new nonradioisotopic method for HLA class II molecular typing
      performed in 96-well plates of the same size as those used in enzyme-linked
      immunosorbent assays (ELISA) and radioimmunoassays (RIA). Biotinylated sequence
      specific oligonucleotide (SSO) probes are bound to avidin-coated plates.
      Digoxigenin-labeled PCR-amplified DNA samples are hybridized, washed and detected
      with a peroxidase conjugated antibody assay. The method was tested by performing
      a partial HLA DQA1 and DQB1 typing on 69 randomly selected blood samples. The
      results are completely concordant with a traditional SSO-PCR typing performed on
      the same samples. This procedure is simple, fast and could be adapted for
      performance in semi-automated or automated fashion using equipment already
      available for ELISA and RIA assays.

PMID- 8267988
TI  - Replacement of bioprostheses by insertion of a mechanical device within the old
      stent.

PMID- 8267989
TI  - Bioprosthesis replacement with mechanical valve implantation on the bioprosthetic
      ring. Surgical and 2D echo considerations.
AB  - Removal of a failing bioprosthesis can be a delicate operation and extensive
      damage can be caused. Eighteen patients with failing bioprostheses underwent
      excision of the leaflets, then the "new" mechanical valve was sewn onto the "old"
      bioprosthetic ring. At follow-up, clinical and 2D color-flow echo-Doppler
      evaluations showed good hemodynamic performance of the mechanical valves.

PMID- 8267990
TI  - Retention of bioprosthetic valve annulus in mitral prosthetic replacement.
AB  - Mitral valve prosthetic replacement carries high mortality rates by modern
      standards, and mitral bioprostheses are particularly prone to degeneration.
      Bioprosthetic replacement may be technically difficult when there is
      calcification of the tissue ingrowth, strut incorporation, or valve-to-annulus
      size mismatch at the primary operation. A "valve-in-valve" technique is described
      where the mechanical prosthesis is implanted in the bioprosthetic annulus in
      order to avoid such difficulties. The results in the first eight patients are
      presented, showing post-operative Doppler-derived transvalvar mean gradients
      between 3.9 mmHg and 7.5 mmHg, and estimated valve areas between 1.9 cm2 and 3.5
      cm2. All patients are alive at between 20 and 30 months (mean 23.6 months) after
      operation, they are without serious post-operative morbidity and are in
      functional class I or II (NYHA classification).

PMID- 8267991
TI  - The value of the stentless biovalve prosthesis. An experimental study.
AB  - Clinical use of the stentless bioprosthesis has not yet been accepted world-wide.
      Experimental studies are scarce. In a study in growing pigs, 23 aortic valve
      replacements were performed (7 stented bioprostheses (STB), 10 stentless
      bioprostheses (SLB) and 6 cryopreserved homografts (CAH)). Valves were studied
      macroscopically and microscopically after explantation. Five animals died between
      1.5 and 4 months after implantation. Two STBs showed extreme calcific
      degeneration. A third STB animal died suddenly: this STB showed only minimal
      leaflet calcification. One SLB was stenosed with a large fibrin deposit in one
      cusp, a second SLB showed slight cusp calcification and three were
      paracommissural tears in one cusp. In all other animals the valves were explanted
      after 5 to 6.5 months. All STBs showed severe calcific degeneration. Five SLBs
      showed mild calcific degeneration, while three others were unaltered after 6
      months. All CAHs were free of calcific degeneration, three were perfect, two had
      a tear in a commisure and another was prolapsed with a fibrin degeneration. The
      speed and extent of valve degeneration were less than in the STB group. The
      stentless design is an important contribution which may result in a higher
      durability of bioprosthetic valves.

PMID- 8267992
TI  - Arrhythmia prophylaxis after coronary artery surgery. A randomised controlled
      trial of intravenous magnesium chloride.
AB  - One hundred and thirty patients undergoing elective myocardial revascularisation
      were randomised to receive an intravenous infusion containing either 50 mmol
      magnesium chloride or placebo during the first 48 h following surgery. Magnesium
      was given to 66 patients and a placebo infusion to 64 patients. Postoperative
      serum magnesium concentrations fell in the placebo group (from 0.83 +/- 0.06 to
      0.79 +/- 0.11 mmol/l) but were elevated in the magnesium group (from 0.82 +/-
      0.05 to 1.2 +/- 0.25 mmol/l). In total, 35 patients (26.9%) had a
      supraventricular arrhythmia, of which 11 were in the magnesium group (16.7%) and
      24 (37.5%) in the placebo group (P = 0.013). Three patients in the magnesium
      group had an episode of ventricular fibrillation and three patients in the
      placebo group had frequent ventricular ectopics. There was one death in the
      magnesium group associated with a perioperative myocardial infarction. This study
      shows that intravenous magnesium supplements reduce the incidence of
      supraventricular arrhythmias following coronary artery surgery.

PMID- 8267993
TI  - Hemodynamic findings in patients with left bundle branch block after myectomy in
      hypertrophic obstructive cardiomyopathy (HOCM)
AB  - To determine the hemodynamic effects of postoperative left bundle branch block
      (LBBB) in patients with hypertrophic obstructive cardiomyopathy (HOCM), we
      investigated 28 patients using Swan-Ganz pulmonary artery catheterization at rest
      and on exercise. Fourteen patients had postoperative LBBB (group A) and 14 had
      undisturbed intraventricular conduction (group B). All patients were examined by
      clinical investigation, electrocardiogram and bicycle ergometer exercise
      preoperatively and postoperatively (mean 6 months). Pulmonary artery pressure and
      pulmonary capillary wedge pressure were continuously measured, stroke volume
      index and cardiac index were obtained by the thermodilution method. All patients
      showed an improvement of their clinical symptoms (NYHA class: 2.8 +/- 0.45 before
      and 1.7 +/- 0.22 after operation) (P < 0.05). The postoperative exercise capacity
      (Watt) increased significantly (P < 0.05) in group A by 38% and in group B by
      30%. The maximum mean pulmonary artery pressure on physical exercise decreased in
      group A from 40.7 +/- 9.1 to 32.5 +/- 8.7 mmHg and in group B from 42.8 +/- 12.4
      to 32.4 +/- 9.2 mmHg (P < 0.05). The maximal stroke volume index and cardiac
      index improved significantly in 9 of 14 patients in each group. Thus, patients
      with HOCM and LBBB after myectomy have a marked improvement in postoperative
      hemodynamics, the results equaling those of patients with undisturbed
      intraventricular conduction.

PMID- 8267994
TI  - Plasma levels of atrial natriuretic factor (ANF) and urinary excretion of ANF,
      arginine vasopressin and catecholamines in children with congenital heart
      disease: effect of cardiac surgery.
AB  - We studied the changes in the plasma concentration of atrial natriuretic factor
      (ANF) and the urinary excretion of ANF, arginine vasopressin (AVP) and
      catecholamines in 22 children with congenital heart disease, divided into two
      groups. Group 1 included 11 children with congestive heart failure (CHF), treated
      with digitalis and diuretics. Group 2 included 11 children without CHF and
      without medical treatment. Each group was compared with a control group of 15
      healthy, age-matched children. The plasma concentration of ANF was raised in both
      groups, but it was significantly higher in group 1 (235.5 +/- 82.9 pg/ml),
      compared to group 2 (48.4 +/- 29.4 pg/ml, P < 0.002). Urinary excretion of ANF
      was measurable in both groups and higher in group 1 (185.9 +/- 116.2 pg/kg per h)
      than in group 2 (48.5 +/- 30.7 pg/kg per h), but not significantly so. Urinary
      excretion of AVP and catecholamines was not different in children with congenital
      heart disease and healthy children. Twenty-four hours after surgery, plasma ANF
      diminished in group 1 (from 235.5 +/- 82.9 to 93.4 +/- 53.8 pg/ml, P < 0.003),
      but did not change in group 2. The urinary excretion of ANF was unchanged in both
      groups. In contrast, urinary excretion of AVP and catecholamines rose
      significantly in both groups. These data show that plasma ANF is increased in
      children with congenital heart disease, even in the absence of CHF. The
      measurement of urinary ANF is less reliable than a plasma assay. The
      postoperative increases in AVP and catecholamine urinary excretions could be
      responsible for the vasoconstriction and water retention typical of the
      postoperative period.

PMID- 8267995
TI  - Experimental tracheal revascularization with omentum.
AB  - We assessed omental revascularization of heterotopic tracheal implants in rats,
      and investigated the influence of factors that can enhance revascularization. The
      trachea of the donor animal was excised in two parts, and each tracheal allograft
      was implanted in the omentum of two recipients. The influence of mechanical
      factors was evaluated by applying traction at both ends of the graft with and
      without drainage of the tracheal lumen, and the influence of pharmacologic
      factors by giving cefonicid, hydrocortisone, cefonicid plus hydrocortisone, or
      cyclosporine and azathioprine during the postoperative period. Revascularization
      of the graft from the omentum with preservation of the tracheal structure was
      established. Graft viability showed significant differences between the tracheal
      implants to which no traction had been applied and those with traction at both
      ends. Tracheal allografts from animals receiving immunosuppressants were
      completely viable and no significant differences were found between the controls
      and animals in this group.

PMID- 8267996
TI  - Evaluation of surgical treatment of pyothorax with special reference to the
      usefulness of the omental pedicle flap method.
AB  - The operative results in a series of 17 patients with pyothorax were reviewed. Of
      these, 10 had chronic empyema (group 1), and 7 had postoperative empyema (group
      2). A single-stage operation was performed in eight patients in group 1
      (decortication in six, thoracoplasty in one, omental plombage in one) and in all
      patients in group 2 (omentopexy in five, thoracoplasty in two). Two-stage
      procedures were performed in two patients in group 1. We obtained favorable
      postoperative results in eight patients in group 1, and in four patients in group
      2. In our series, good results were not obtained by thoracoplasty alone; however,
      satisfactory results were achieved by short-term management in patients treated
      with the omental method. We think this series demonstrates the value of the
      omental pedicle flap method, which prevents loss of function due to a defective
      organ and offers excellent therapeutic results following an easy operative
      procedure. Further active application of this method can be expected in the
      management of thoracic disorders.

PMID- 8267997
TI  - University of Wisconsin solution and human saphenous vein graft preservation:
      preliminary anatomic report.
AB  - Endothelial damage of human saphenous vein (HSV) during the preparation for
      bypass grafting could affect graft patency. Improving the preservation of HSV
      could provide a longer and better patency of coronary artery bypass grafts. An
      electron microscopic comparative analysis of the effects of three different
      preservatives on HSV morphology was carried on in order to determine the best
      method to prevent or minimize possible endothelial damage. Distal segments of
      HSVs were harvested from 15 patients with a "no-touch" technique. Each segment
      was divided into seven specimens after a low pressure distension with saline
      solution. The first of them was fixed immediately after harvesting with 2.5%
      glutaraldehyde solution, for basal evaluation. Three were fixed after 30 min and
      three after 5 h preservation at 4 degrees C in a) autologous, oxygenated, and
      heparinized blood (AOHB), b) heparinized saline solution with papaverine (HSSP)
      and c) University of Wisconsin solution (UWS). The specimens preserved in AOHB
      showed marked endothelial cell detachment and endothelial cell loss after both
      preservation times (30 min and 5 h). The specimens preserved in HSSP for 30 min
      showed no alteration in endothelium in 12 cases, while a partial endothelial
      detachment with intracellular edema was present in the last 3 cases; all 5 h
      specimens showed only a few remnants of endothelial cells. The specimens
      preserved in UWS for 30 min showed a morphology comparable to specimens preserved
      in the saline solution for the same time; in the 5 h specimens a well preserved
      endothelium was found in 11 cases and partial endothelial detachment and
      subendothelial edema in the other 4.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8267998
TI  - Magnetic resonance imaging of blunt traumatic rupture of the right hemidiaphragm.
AB  - A patient suffering from blunt traumatic rupture of the right hemidiaphragm is
      presented. Chest radiography and computed tomography (CT) suggested the type of
      injury, but magnetic resonance imaging (MRI) established unequivocally the
      correct preoperative diagnosis.

PMID- 8267999
TI  - Chylothorax as a complication of harvesting the left internal thoracic artery in
      coronary artery bypass surgery.
AB  - A patient is described with chylothorax after harvesting the left internal
      thoracic artery for coronary artery bypass surgery. Conservative treatment with a
      medium chain triglycerides diet and tube thoracostomy was not only unsuccessful,
      but also resulted in the complications of malnutrition and empyema. We recommend
      early surgical treatment of chylothorax after coronary bypass surgery with the
      use of an internal thoracic artery.

PMID- 8268000
TI  - Simultaneous oesophagectomy and CABG for cancer and ischaemic heart disease.
AB  - We describe a case of simultaneous coronary artery bypass grafting (CABG) and
      oesophagectomy for ischaemic heart disease and oesophageal carcinoma.

PMID- 8268001
TI  - Transaortic division of the mitral subvalvar apparatus.
AB  - Adequate exposure of the mitral valve can be difficult to obtain through a median
      sternotomy. A variety of techniques have been described to facilitate exposure in
      this situation. This report describes the use of trans-aortic technique which
      allows easy and accurate division of the mitral subvalvar apparatus. The mitral
      valve can then be approached through a left atriotomy, everted and the excision
      completed.

PMID- 8268002
TI  - Intercostal nerve block, interpleural analgesia, thoracic epidural block or
      systemic opioid application for pain relief after thoracotomy?

PMID- 8268003
TI  - Ribonucleotide reductases and their occurrence in microorganisms: a link to the
      RNA/DNA transition.
AB  - The evolution of a deoxyribonucleotide synthesizing ribonucleotide reductase
      might have initiated the transition from the ancient RNA world into the
      prevailing DNA world. At least five classes of ribonucleotide reductases have
      evolved. The ancient enzyme has not been identified. A reconstruction of the
      first ribonucleotide reductase requires knowledge of contemporary enzymes and of
      microbial evolution. Experimental work on the former focuses on few organisms,
      whereas the latter is now well understood on the basis of ribosomal RNA
      sequences. Deoxyribonucleotide formation has not been investigated in many
      evolutionary important microorganisms. This review covers our knowledge on
      deoxyribonucleotide synthesis in microorganisms and the distribution of
      ribonucleotide reductases in nature. Ecological constraints on enzyme evolution
      and knowledge deficiencies emerge from complete coverage of the phylogenetic
      groups.

PMID- 8268004
TI  - Bacterial solute transport proteins in their lipid environment.
AB  - The cytoplasmic membrane of bacteria is a selective barrier that restricts entry
      and exit of solutes. Transport of solutes across this membrane is catalyzed by
      specific membrane proteins. Integral membrane proteins usually require specific
      lipids for optimal activity and are inhibited by other lipid species. Their
      activities are also sensitive to the lipid bilayer dynamics and physico-chemical
      state. Bacteria can adapt to changes in the environments (respective temperature,
      hydrostatic pressure, and pH) by altering the lipid composition of the membrane.
      Homeoviscous adaptation results in the maintenance of the liquid-crystalline
      phase through alterations in the degree of acyl chain saturation and branching,
      acyl chain length and the sterol content of the membrane. Homeophasic adaptation
      prevents the formation of non-bilayer phases, which would disrupt membrane
      organization and increase permeability. A balance is maintained between the
      lamellar phase, preferring lipids, and those that adopt a non-bilayer
      organization. As a result, the membrane proteins are optimally active under
      physiological conditions. The molecular basis of lipid-protein interactions is
      still obscure. Annular lipids stabilize integral membrane proteins. Stabilization
      occurs through electrostatic and possibly other interactions between the lipid
      headgroups and the charged amino acid residues close to the phospholipid-water
      interface, and hydrophobic interactions between the fatty acyl chains and the
      membrane-spanning segments. Reconstitution techniques allow manipulation of the
      lipid composition of the membrane in a way that is difficult to achieve in vivo.
      The physical characteristics of membrane lipids that affect protein-mediated
      transport functions have been studied in liposomal systems that separate an inner
      and outer compartment. The activity of most transport proteins is modulated by
      the bulk physical characteristics of the lipid bilayer, while specific lipid
      requirements appear rare.

PMID- 8268005
TI  - Iron uptake mechanisms of pathogenic bacteria.
AB  - Most of the iron in a mammalian body is complexed with various proteins.
      Moreover, in response to infection, iron availability is reduced in both
      extracellular and intracellular compartments. Bacteria need iron for growth and
      successful bacterial pathogens have therefore evolved to compete successfully for
      iron in the highly iron-stressed environment of the host's tissues and body
      fluids. Several strategies have been identified among pathogenic bacteria,
      including reduction of ferric to ferrous iron, occupation of intracellular
      niches, utilisation of host iron compounds, and production of siderophores. While
      direct evidence that high affinity mechanisms for iron acquisition function as
      bacterial virulence determinants has been provided in only a small number of
      cases, it is likely that many if not all such systems play a central role in the
      pathogenesis of infection.

PMID- 8268006
TI  - Recent advances in elucidation of biological corrinoid functions.
AB  - Eleven adenosylcorrinoid-dependent rearrangements and elimination reactions have
      been described during the last four decades of vitamin B12 research. In contrast,
      only the cobamide-dependent methionine synthase was well established as a
      corrinoid-dependent methyl transfer reaction. yet, investigations during the last
      few years revealed nine additional corrinoid-dependent methyltransferases. Many
      of these reactions are catalyzed by bacteria which possess a distinct C1
      metabolism. Notably acetogenic and methanogenic bacteria carry out such methyl
      transfers in their anabolism and catabolism. Tetrahydrofolate or a similar
      pterine derivative is a key intermediate in these reactions. It functions as
      methyl acceptor and the methylated tetrahydrofolate serves as a methyl donor.

PMID- 8268007
TI  - Biological properties of phocine distemper virus and canine distemper virus.
AB  - Morbilliviruses constitute a major threat to the health of animal and man. To
      date the Morbillivirus genus in the Paramyxoviridae family comprises five
      established members, namely canine distemper virus (CDV), phocine distemper virus
      (PDV), measles virus (MV), rinderpest virus (RPV), and peste-des-petits-ruminants
      virus (PPRV). In addition, morbillivirus candidates infecting aquatic mammals
      were recently discovered. The present review on the biology of morbilliviruses
      focuses on knowledge gained by our group in studies on PDV and CDV. The aims of
      these studies were: i) to investigate the biological properties of the recently
      recognized PDV, which was found to be the primary etiology of epidemics with high
      mortality in seals in Western Europe, ii) to extend our knowledge of the
      biological properties of CDV. The morbillivirus particle is enveloped. The
      helical nucleocapsid core contains a single-stranded, non-segmented RNA genome of
      negative sense of 15 to 16 kilobases in length. The genome is organized in six
      transcriptional units or genes. Overall, the studies of the genome of PDV
      revealed a genetic map principally fitting with that determined for other
      morbilliviruses. The nucleotide and deduced amino acid sequences have been
      determined for five PDV genes named in analogy with the encoded structural
      proteins of other morbilliviruses in the order: 3'N(1683)-P(1644)-M(1443)-F(2206)
      H(1952)-L5' (The figures in brackets denote nucleotide lengths of the genes of
      the Danish PDV isolate). The L gene (covering approximately 8900 nucleotides)
      remains to be sequenced. The six genes are likely to code for at least eight
      distinct proteins. The nucleocapsid (N) protein was found to consist of 523 amino
      acids in PDV. The following gene of the transcription map encoded the P protein
      of 507 amino acid residues. Similar to other morbilliviruses, the P gene of PDV
      was shown to have additional coding capacity for two distinct proteins V (299
      amino acids) and C (174 amino acids). The results presented provide evidence for
      editing at transcript of the PDV P gene by insertion of nontemplated G residues
      at a specific site. The edited version of the mRNA was found to encode the
      cystein-rich V protein. The three envelope-associated proteins of PDV were
      predicted to consist of 335 (M), 537 (F0) and 607 (H) amino acid residues. The
      nucleotide and deduced amino acid sequences of the N, P, M, F, and H genes of PDV
      were aligned with corresponding sequences of other established members of the
      genus Morbillivirus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268008
TI  - Visualizing the natural dentition.

PMID- 8268009
TI  - Considerations for successful single tooth implant restorations.

PMID- 8268010
TI  - Facial/lip reproduction system for anterior restorations.

PMID- 8268011
TI  - The difficult patient stress syndrome: Part II.

PMID- 8268012
TI  - The failing and failed implant: a clinical, microbiologic, and treatment review.
AB  - The goal of implant therapy is to restore a physiologic state of health to a
      compromised dentition. A successfully osseointegrated fixture is surrounded by
      healthy alveolar bone and gingival tissues.

PMID- 8268013
TI  - American Society for Laser Medicine and Surgery, 13th annual meeting. New
      Orleans, Louisiana, April 18-20, 1993. Abstracts.

PMID- 8268014
TI  - An Australian agenda for adolescent health in the 1990s.

PMID- 8268015
TI  - Interdisciplinary education in adolescent health.
AB  - To date, evidence suggests that, across disciplines, the educational preparation
      of health professionals has not kept pace. Those involved in the education of
      clinicians, researchers, and educators in adolescent health are currently faced
      with the need to rethink traditional educational strategies. Concurrent with a
      shift in the primary causes of morbidity and mortality in adolescence, from
      infectious to social aetiologies, is an emerging clarity about the success of
      integrated comprehensive service settings in addressing adolescents' health
      needs. One approach for better preparing health providers to work in multiservice
      settings is to provide training in interdisciplinary programmes. Various models
      for interdisciplinary education in adolescent health exist; characteristics
      common to all are delineated. Whereas obstacles to the creation and
      implementation of interdisciplinary programmes, including institutional,
      financial, and educational barriers, are great, the need to overcome them is
      critical if we are to keep pace with the changing needs of the adolescent
      population.

PMID- 8268016
TI  - Failing a generation: the impact of culture on the health and well-being of
      youth.
AB  - Trends in suicide, mental disorders, drug abuse and crime suggest western
      industrial societies are becoming increasingly harmful to psychological and
      social well-being. These trends are usually explained in personal, social and
      economic terms; problems in personal relationships, poverty, family conflict and
      breakdown, unemployment, homelessness, education pressures and demographic
      changes. The contribution of the culture of western societies to our worsening
      predicament, most evident among our youth, may be seriously under-estimated
      because it is more difficult to assess. Yet modern western culture arguably fails
      to meet the most fundamental requirements of any culture: to provide a sense of
      belonging and purpose, and so a sense of meaning and self-worth, and a moral
      framework to guide our conduct. This cultural failing may be more apparent in
      Australia, and other 'new' western nations because they are young, heterogeneous
      peoples, without a long, shared cultural heritage or a strong sense of identity.

PMID- 8268017
TI  - Suicidal adolescents: lessons to be learned from early intervention.
AB  - In France as in most developed countries, suicide is the second leading cause of
      adolescent deaths. Suicide attempts are estimated to be at least 30 times more
      common than completed suicides. Adolescent suicidal behaviours are a most
      sensitive subject. Fear, defensive attitudes, and lack of consensus as to
      management are detrimental to a good understanding of and an appropriate approach
      to the problems involved. Our adolescent medicine experience with several hundred
      adolescent victims of suicide attempt shows that most come from troubled or
      abusive environments, most did not clearly intend to die and are asking for some
      help. Only a minority appear to be mentally ill and need inpatient psychiatric
      care. These patients are best approached when hospitalized like any other
      adolescent and offered a thorough health screening, within an integrated and
      multidisciplinary framework which allows working with both the patient and his
      family.

PMID- 8268018
TI  - Warning! Schools can damage your health: alienation from school and its impact on
      health behaviour.
AB  - An international study of health behaviour among school-age children was co
      ordinated by the World Health Organization (WHO). The data were obtained from a
      self-completion questionnaire examining key health behaviours and associated
      psycho-social variables obtained from representative samples of young people in
      school aged 11.5, 13.5, and 15.5 years. The analysis focuses on the relationship
      between older (15.5 years) students' attitudes towards school and health
      behaviours such as regular smoking, alcohol use, physical activity and food
      choices. The data show a strong and progressive relationship between indicators
      of 'alienation' from school, and health compromising behaviours among school
      students from Australia and Wales. This relationship is most obvious with the
      'abusive' behaviours of smoking and alcohol misuse. Summary data for nine other
      countries in the WHO study indicate that this relationship is found consistently
      across all countries in the study. This substantial minority of students
      (approximately 30% varying between countries) represents an important target
      population for efforts to promote healthy lifestyles. Traditional school health
      education is seen as insufficient to tackle this task and recommendations are
      made concerning change to the school environment and ethos, and the need to reach
      young people in their home and community settings.

PMID- 8268019
TI  - The impact of caring and connectedness on adolescent health and well-being.
AB  - This study of over 36,000 7th-12th grade students focused on protective factors
      against the quietly disturbed and acting out behaviours, which together represent
      the major social morbidities of adolescence. Multivariate models developed
      separately for girls and boys repeatedly demonstrated the protective function of
      caring and connectedness in the lives of youth, particularly a sense of
      connectedness to family and to school. A sense of spirituality, as well as low
      family stress (referring to poverty, unemployment, substance use and domestic
      violence) also functioned as protective factors. Measures of caring and
      connectedness surpassed demographic variables such as two parent vs single parent
      family structure as protective factors against high risk behaviours.
      Interventions for youth at-risk must critically examine the ways in which
      opportunities for a sense of belonging may be fostered, particularly among youth
      who do not report any significant caring relationships in their lives with
      adults.

PMID- 8268020
TI  - Adolescent resilience: the potential impact of personal development in schools.
AB  - The challenges and stresses faced by adolescents include entry into secondary
      school, the development of adolescent sexuality, family conflicts, parental
      mental illness, socio-cultural factors, substance use and abuse, work and career
      abuse, social and antisocial behaviour, and the carry-over of problems from
      childhood. The ways in which programmes through schools can address these issues,
      enhance resilience and promote adolescent mental health are discussed. The
      potential of personal development programmes could be utilized to this end, with
      targeted educational and group initiatives and evaluation of outcomes.

PMID- 8268021
TI  - Family relationships and the development of social competence in adolescence.
AB  - Resilient adolescents are notable for their social competence, which enables them
      to form and maintain close relationships. The evidence is that adolescents'
      social competence is derived from their experience of close relationships within
      their family. On the basis of structured interviews, adolescents' working models
      of attachments can be categorized into secure, dismissive, or pre-occupied. These
      attachment styles are associated with very divergent beliefs about the self and
      others, with differing patterns of emotion regulation and with differing risk
      profiles for maladjustment. Parenting styles and family relationships appear to
      have considerable influence on attachment behaviour. Further evidence for the
      importance of the family comes from research on ego development. Family level
      behavioural patterns have been discerned from family research interviews which
      are associated with stagnation or advancement in ego development during
      adolescence. Though the results suggest causal connections, the direction of
      effects is far from clear. Longitudinal research underpins the importance of
      childhood temperament as a contributing factor to the quality of the family
      environment that the child and then adolescent experiences.

PMID- 8268022
TI  - Issues of immigration for the health and adjustment of young people.

PMID- 8268023
TI  - Street youth: social imbalance and health risks.
AB  - Street youth are children and adolescents who express, through their bodies and
      lives, misery and social abandonment. Paradoxically, they are also the embodiment
      of resistance and survival strategies in a very unfavourable environment. The
      current deterioration of citizens' rights and the social inequalities reflect the
      consequences of vicious cycles of economic and political crises in Brazil.
      Poverty conditions reach levels of misery and create strategies of survival that
      create multiple high-risk health situations. Many other factors make up the
      complex dynamics of these conflicts in which the limit of rejection and social
      abandonment are expressed in the violence of extermination. The proposals and
      solutions cannot be dissociated from the reality of this country and of the
      street youth lifestyle. Effective health education within this social context is
      difficult, but possible with the development of appropriate audio-visual material
      and the dissemination of preventive health information. A commitment to action
      must permeate all levels of decision making within the health system and in our
      society, for it is the essence of democracy and human rights.

PMID- 8268024
TI  - Suicide in the young.
AB  - Suicide in the young is not a new phenomenon. There have been increases in young
      males but not young females, and the geographic distribution varies. Although
      sociological issues are of importance, there are substantial data attesting to
      the presence of psychiatric illness in the overwhelming majority of those who
      commit suicide. While such illness may not be a sufficient cause for suicide to
      occur, it would appear to be a necessary one. Treatments are available.

PMID- 8268025
TI  - Issues of transition to adult care.
AB  - A survey was carried out on adolescents with insulin dependent diabetes mellitus,
      aged 15 to 18 years, to elicit their views on the process of transfer from
      paediatric to adult care. The survey provided information on what they expected
      from a health service during this period of their life, their views on the role
      of specialist physicians and other health professionals and their preferred age
      for transfer from a paediatric to an adult service. Young people value continuity
      of care by a physician whom they trust. They expect confidentiality and privacy,
      some degree of informality and optimal waiting room conditions when they attend
      for consultation. Almost all suggested that transfer of care should be after the
      age of 17 years. An understanding of the views and expectations of young people
      with a chronic illness such as diabetes should assist those who are responsible
      for the development of health care. It is recommended that transition services
      for young people with a chronic illness be developed at those children's and
      adult hospitals that provide specialist care for them.

PMID- 8268026
TI  - Health issues for aboriginal youth: social and cultural factors associated with
      resilience.
AB  - Research into Aboriginal health has tended to focus on the morbidity of babies
      and young children, or on the chronic illnesses of adults. Adolescent Aborigines
      are rarely the target of health research. While health services for Aboriginal
      people, even in remote areas, have improved enormously over the last few years
      with the provision of Aboriginal-controlled organizations, health services alone
      do not prevent the major causes of morbidity. In any case, young people,
      particularly adolescent boys, are poor users of these facilities. The major
      causes of adolescent Aboriginal morbidity and mortality are preventable: they
      have to do with ways of living, with the social, cultural and physical
      environments which surround adolescents. The paper draws on anthropological
      fieldwork which pays close attention to these issues. The paper examines the
      concept of 'adolescence' among Aboriginal groups, and explores the reasons for
      the resilience of some populations to a particular health problem, that of petrol
      sniffing among the young.

PMID- 8268027
TI  - Taking a chance on love: risk behaviour of Sydney street youth.
AB  - Two samples of street youth from the inner city area of Sydney, ranging in age
      from 13 to 20, with a mean of 17, were surveyed via a lengthy questionnaire. The
      first survey in 1989/90 (n = 92; 66 males, 26 females) revealed high levels of
      physical and sexual abuse; violence and negative relationships as major factors
      in leaving home; safe sexual practice not common (other than for those
      prostituting); polydrug use widespread and heavier for females; some needle
      sharing by injecting drug users (IDU). Second survey, 190/91 (n = 100; 70 males,
      30 females), confirmed previous picture, but found changes in immunodeficiency
      virus (HIV) risk behaviours: needle sharing reduced; for those prostituting an
      increase in safe sexual practices with clients; reduction in regular safe sexual
      practices with non-paying partners. IDU was significantly linked to prostitution
      as was needle sharing. Some changes are in an encouraging direction, but more
      preventive work is needed focusing on safe behaviours with non-paying partners
      and how to initiate and negotiate these. More qualitative or ethnographic
      research could better inform such efforts and, indigenous strategies deserve
      recognition.

PMID- 8268028
TI  - Future challenges for behavioural research in adolescent health.
AB  - Risk to health during adolescence is more likely due to behaviour than disease.
      Problems arise because behaviour is distally removed from its consequences and
      negative reinforcement is not contiguous with it. The paper reviews recent
      research and the problems faced by health workers in devising educational
      programmes when behaviour, in the cultural value system of adolescents, is
      present-oriented and outcomes are future-oriented. The challenge to the
      behavioural scientist is to develop health education programmes which have
      personal meaning to adolescents. Working against this aim are such processes as
      adolescent taboos, locus of control, the personal fable, risk behaviours and
      social-cognitive immaturity. Suggestions are made for research scientists to
      devise and evaluate programmes to change the operational liberalism of adolescent
      behaviour by installing more ideologically conservative attitudes in the hope
      that behavioural change will follow.

PMID- 8268029
TI  - [The role of immunology in the nervous system].

PMID- 8268030
TI  - [Myasthenia gravis and its immunological aspects].

PMID- 8268031
TI  - [Immunological aspects of multiple sclerosis].

PMID- 8268032
TI  - [Therapeutic plasma exchange for neuroimmunological disorders].

PMID- 8268033
TI  - [Serotonergic mechanisms of hippocampal kindled seizures in cats--effects of 1
      (2,5-dimethoxy-4-iodophenyl)-2-aminopropane and ketanserin].
AB  - Based on our previous findings that a serotonin (5-HT) precursor L-5
      hydroxytryptophan and a 5-HT1 a receptor agonist 8-hydroxy-2-(di-n-propylamino)
      tetralin can suppress seizures kindled from the feline hippocampus (HIP), we have
      suggested that 5-HT1 a receptors play an inhibitory role in HIP seizure
      generation. In order to clarify the role of 5-HT2 receptors in epilepsy, the
      present study examined the effects of a 5-HT2 receptor agonist 1-(2,5-dimethoxy-4
      iodophenyl)-2-amino-propane(DOI) and a 5-HT2 receptor antagonist ketanserin on
      HIP-kindled seizures. Following the completion of HIP kindling, five cats
      received intravenous injections of 0.9% saline, DOI (1.0mg/kg) or ketanserin
      (1.0mg/kg). Electrical stimulation at the generalized seizure triggering
      threshold was delivered to the kindled HIP 15 min after drug administration. The
      anticonvulsant effects were assessed by the behavioral seizure stage,
      afterdischarge duration, latency to the onset of stages 4 and 6, and duration of
      a generalized tonic-clonic convulsion (GTC). Although no significant change was
      found in the seizure stage following the administration of either drug, both DOI
      and ketanserin significantly altered the latency for seizure generalization. DOI
      significantly reduced the latency to the onset of stage 6 GTC as compared with
      saline, with a significant reduction in the afterdischarge duration. In contrast,
      ketanserin significantly increased the latency to the GTC onset as compared with
      saline. Neither the latency of the stage 4 onset nor the GTC duration was
      significantly affected by these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268034
TI  - [Visualization of brain function using MRI-MR functional brain imaging].
AB  - The effects of photic stimulation on the visual cortex of human brain were
      studied by means of gradient-echo magnetic resonance imaging (MRI). Fast low
      angle shot (FLASH) MRI was used to monitor changes in brain oxygenation in the
      human visual cortex during photic stimulation (PS). Whole-body 1.5 T clinical MR
      system was used. Elevation of image intensity up to 2% was observed in primary
      and associative visual cortex, corresponding to an increase of blood oxygenation
      in regions of increased neural activity. After the PS was switched off, the MR
      signal fell below the pre-PS baseline level, which may be understood as an
      displacement of the oxygen-hemoglobin dissociation curve (the Bohre effect).

PMID- 8268035
TI  - [Cerebral blood flow disorder in elderly patients with diabetes mellitus].
AB  - We studied changes due to aging in carotid and cerebral arterial blood flows, and
      compared the difference between healthy adults and diabetics using a ultrasonic
      quantitative blood flow measurement system (QFM 2000 XA). Aging caused the
      carotid blood flow, blood velocity and diameter excursion rate on the carotid
      wall to decrease, and its diameter to enlarge. Both cerebrovascular resistance
      and capacitance obtained from simulation models of blood pressure waves,
      increased with aging. Cerebral blood flows in aged healthy adults was not
      significantly different from those in aged diabetics, but clearly different from
      those in aged diabetics with abnormal findings on MRI. When right and left
      cerebral blood flows were markedly different, abnormality was observed on brain
      MRI. This well agreed with findings on cerebral blood flow scintigrams (SPECT)
      obtained from several patients. The ultrasonic quantitative blood flow
      measurement system is considered a useful screening tool before CT or MRI
      examinations.

PMID- 8268036
TI  - [The severity of dementia and brainstem auditory evoked potentials--the amplitude
      of waves I, III and V].
AB  - The correlation between the severity of dementia and the amplitudes of brainstem
      auditory evoked potentials (BAEPs) was studied. The subjects were 78 patients
      with dementia (20 males, 58 females) whose mean age was 80.5 +/- 6.7 years.
      Normal subjects were 9 elderly persons (2 males, 7 females) whose mean age was
      79.2 +/- 6.0 years. The amplitudes of wave-I, -III and -V were measured. As for
      individual differences: (1) The amplitudes of BAEPs in the male group were lower
      than that in the female group, there was no significant difference. (2) The
      amplitudes of wave-V in female patients with vascular dementia were significantly
      lower than that of degenerative dementia. (3) The amplitudes of wave-III reduced
      as the duration of illness prolonged. Dividing the patients into three groups
      according to the severity of dementia which are mild, moderate and severe. (4)
      The amplitudes of the wave-V reduced significantly as the severity of dementia
      advanced. There was a significantly positive correlation between the amplitudes
      of the wave-V and the Hasegawa's dementia scores (r = 0.404759, p < 0.05) Based
      upon the above results, the brainstem dysfunction might progress with the
      severity of dementia.

PMID- 8268037
TI  - [A case of apnea attacks due to an unilateral infarction in the right medulla
      oblongata].
AB  - We described a patient presenting with apnea attacks due to an unilateral small
      infarction in the right medulla oblongata. The patient was a 55-year-old man and
      was referred to our hospital because of severe headache and progressive left
      hemiparesis. Neurological examinations revealed left hemiparesis and the
      impairment of pain, touch, temperature and vibration sense in the left side of
      his body. Position sense was normal. Cranial nerves were intact including the
      trigeminal nerve. Ataxia was not noted. After an admission, the patient suffered
      from three episodes of apnea attack of sudden onset followed by cardiac arrest
      and convulsion. Magnetic resonance imaging demonstrated a clearly circumscribed
      small oblique lesion situated in the caudal lateral tegmental portion to the
      rostral ventromedial part of right medulla oblongata . The right vertebral artery
      was not visualized by magnetic resonance angiography. Serial computed tomography
      scans failed to identify this small lesion. We conclude that apnea attack in the
      present patient represents a central type apnea caused by the unilateral damage
      of the respiratory center in the medulla oblongata.

PMID- 8268038
TI  - [A case of low grade glioma with Takayasu disease (aortitis syndrome)].
AB  - We experienced a rare case of Takayasu disease with low grade glioma. A 36 year
      old female had an episode of right hemiconvulsion. On admission, she complained a
      slight memory disturbance, urination difficulty and motor weakness of right
      extremities. CT scan demonstrated a low density lesion in the left frontal lobe.
      MRI showed an inhomogeneous low intense mass on T 1 WI and a homogeneous high
      intense mass on T2 WI in the same site. No abnormal contrast enhancement was
      observed in both CT and MRI. Bilateral carotid angiograms demonstrated a filling
      defect of the left anterior cerebral artery. An aortogram revealed moderate
      stenosis of the left carotid artery and the brachiocephalic artery, and complete
      obstruction of the left subclavian artery. CT-guided stereotactic biopsy was
      performed using BRW stereotactic system and histological diagnosis was
      astrocytoma grade II. She was followed by interstitial irradiation of 50 Gy at
      tumor periphery for 10 days. Her neurological symptoms gradually improved, and
      she is doing well without neurological deficits at the time of this report. The
      CT scan obtained 13 months after the brachytherapy revealed a decrease in the
      extent of low density. Brachytherapy seems to be useful for patients with low
      grade glioma in the eloquent area of the brain.

PMID- 8268039
TI  - [Subacute subdural hematoma--reexamination of mechanism by CT and MRI findings].
AB  - We have already reported about the importance of establishing the concept of
      subacute subdural hematoma. But the mechanism by which this disease develops has
      not as yet been elucidated fully. In one case of subacute subdural hematoma, we
      were able to perform CT and MRI over time and obtained findings which were of use
      in studying the mechanism of development. The case was a 56-year-old male. He
      developed with seizure. CT on admission revealed acute subdural hematoma and
      subarachnoid hemorrhage. But neurological deficits were absent. So he was treated
      conservatively. On the 16th hospital day there appeared seizure, anisocoria and
      an increase in the mass sign due to subdural hematoma was noted on CT, so a
      diagnosis of subacute subdural hematoma was made. Cerebrospinal fluid was
      considered accountable for the increase in the mass sign judging from the
      findings of CT and MRI each performed over time. It was surmised that subdural
      effusion developed concurrently in the subacute stage. Three conditions, namely,
      presence of (1) arachnoid tear, (2) clots, (3) no intracranial hypertension are
      considered important as the mechanism by which subacute subdural hematoma
      develops.

PMID- 8268040
TI  - [Spike discharge detected by intra-arterial electroencephalography from intra
      arterial guide wire in temporal lobe epilepsy].
AB  - The implantation of electrodes for intracranial electroencephalography (EEG)
      recording as presurgical evaluation of patients with intractable epilepsy is at
      present most important for planning epilepsy surgery. This method is most
      effective in temporal lobe epilepsy. We carried out intracranial EEG by means of
      insulated micro guide wire for endovascular surgery in two temporal lobe epilepsy
      cases, and spike discharges could be detected in lesional medial temporal lobe.
      Case 1 is a 29 year-old-male suffered from intractable complex partial seizure
      (CPS) for 18 years. He was diagnosed as left temporal lobe epilepsy and performed
      removal of amygdala, hippocampus, parahippocampal gyrus and fusiform gyrus. Case
      2 is a 16 year-old-lady suffered from drug resistant CPS for 4 years. Under the
      diagnosis of right temporal lobe epilepsy, temporal lobectomy was performed. As
      the presurgical evaluation, under the implantation of subdural strip electrode in
      both cases, we carried intra-arterial EEG after angiography. Seeker Lite-10 guide
      wire was insulated with Tracker-10 unibody infusion catheter at sphenoidal
      portion of middle cerebral artery, and frequent interictal spike discharge was
      detected in lesional medial temporal lobes by two methods simultaneously.

PMID- 8268041
TI  - [A 66-year-old man with backache and progressive difficulty of gait].
AB  - We report a 66-year-old man with progressive spinal paraplegia. He was well until
      June of 1991 when he had an onset of backache and right chest pain. On August 25,
      he lost sensation to void and he became unable to urinate. On the same day, he
      noted weakness in his legs which became progressively worse, and he was admitted
      to our hospital. Past medical history included diabetes mellitus which was found
      3 years previously. He had upper gastrointestinal series 2 months before, which
      revealed a normal study. On admission, he was alert and general physical
      examination was unremarkable. Neurological examination revealed a mentally sound
      man with normal higher cerebral functions. Cranial nerves were also intact. He
      was unable to walk. No muscle atrophy was noted, but he had moderate to marked
      (2/5) weakness in both legs. No ataxia was noted in the upper extremities. Jaw
      jerk was normal, however, deep reflexes in the upper extremities were decreased,
      and absent in the lower extremities Babinski sign was present bilaterally. All
      sensory modalities were diminished below the Th 6 dermatome. No meningeal sign
      was present. Emergency myelography was performed on the day of admission, which
      revealed complete block from the Th4 to Th8 segments. CSF taken at that time was
      xanthochromic, positive Queckenstedt test containing 1,133 mg/dl of protein, 54
      mg/dl of sugar and 1/3 microliters of lymphocyte. On August 31, laminectomy was
      performed from Th5 to Th7. The spinal bones in this area was very fragile and
      hemorrhagic. A soft yellowish vascular-rich tissue was surrounding the spinal
      cord in the epidural space. Despite surgery his weakness in legs worsened, and he
      became paraplegic by September 10th. He became somnolent with disorientation to
      time. In the subsequent course, he developed metabolic acidosis on September 26.
      On September 28, he became anuric and hypotensive. He expired later on that
      day.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8268042
TI  - Parathyroid storm: immediate recognition and pathophysiological considerations.
AB  - A 56-year-old white man was referred for evaluation of severe hypercalcemia
      following a three-week history of progressive weakness, nausea, and depression.
      Initial laboratory results showed serum total and ionized calcium (Ca++) values
      of 5.3 and 2.6 mmol/l, respectively. A short intact PTH assay was immediately
      performed and an extremely high value was obtained in just 30 min (1315 ng/l,
      normal values 6.4-70.4). The patient was therefore treated with saline solution
      and with salmon calcitonin (1200 IU/day, half by continuous i.v. infusion and
      half by i.m. route) for 10 days. There was a sudden decrease of both Ca++ and
      intact PTH during the first six days; then there was a trend to reach a steady
      state until parathyroidectomy was performed. After withdrawal of calcitonin
      therapy it was possible to observe a positive uncoupling between bone formation
      (serum alkaline phosphatase and osteocalcin) and resorption (serum tartrate
      resistant acid phosphatase) markers. On day 35 the patient underwent neck
      exploration, and an enlarged lower left parathyroid gland was removed that on
      macroscopic examination revealed the presence of a haemorrhagic cyst; microscopic
      appearance was suggestive of a previous glandular infarction. This is the first
      time the daily clinical course of a parathyroid crisis has been documented.
      Furthermore, changes of biomarkers of bone turnover following calcitonin therapy
      show that high doses of the hormone may cause a prolonged positive uncoupling of
      the two processes of bone remodeling.

PMID- 8268043
TI  - A unique case of adult hypophosphatemic osteomalacia.
AB  - A 36-year-old Russian man presented with neck and low back pain in September
      1990. He was of normal stature, and there were no stigmata of rickets. The family
      history was negative for bone disease. He was found to have hypophosphatemia (2.3
      mg/dl), impaired phosphate reabsorption (TmP/GFR 2.08), hyperphosphatasemia (254
      IU/l), normocalcemia, normal vitamin D metabolite levels, and secondary
      hyperparathyroidism. Clinically, his spinal movements were quite impaired and
      there was moderate proximal muscle weakness. On skeletal radiographs, there was
      generalized osteosclerosis and multiple ligamentous calcifications. Transiliac
      biopsy was diagnostic for severe osteomalacia. He was treated with oral phosphate
      (240 mEq daily) and calcitriol (4 micrograms daily) with resultant very slow
      clinical, biochemical, and histomorphologic improvement. The patient had
      hypophosphatemic osteomalacia with some features of X-linked hypophosphatemia,
      but sporadic and of relatively late onset. The osteopenia, height loss,
      incapacitating weakness, and glycinuria that are characteristics of sporadic
      adult onset nonfamilial hypophosphatemia, with or without an associated tumor,
      and the low serum calcitriol levels that may be an additional characteristic of
      tumor-induced osteomalacia were absent. Other known causes of acquired renal
      tubular dysfunction were ruled out. The etiology, pathogenesis, and nosology of
      the disorder remain obscure, but treatment based on experience with other forms
      of hypophosphatemic osteomalacia was ultimately effective.

PMID- 8268044
TI  - Ultrastructural alterations and retention of the C-propeptide of type II collagen
      in human chondrocytes exposed in vitro to brefeldin A.
AB  - Normal human chondrocytes grown in vitro were exposed to 10 micrograms/ml
      Brefeldin A (BFA) for 24 h, 1 microgram/ml for 4 h, or 0.1 microgram/ml for 4 h
      and evaluated for ultrastructural alterations. BFA in the amount of 0.1
      microgram/ml resulted in vacuolization, disappearance of the Golgi, and moderate
      increases in rough endoplasmic reticulum (rER) vesicles. After 1 microgram/ml BFA
      exposure large interconnected cisternae were identified. BFA treatment of 10
      micrograms/ml was associated with large dilated ER cisternae which contained
      material of variable electron densities. Immunocytochemical localization showed
      markedly increased type II procollagen intracellular retention in BFA-treated
      cells. High dose BFA-treated cells showed ultrastructural similarities to those
      seen in the skeletal dysplasia hypochondrogenesis. Results presented here show
      that in vitro culture of normal human chondrocytes results in retention of the C
      propeptide of type II collagen and marked alterations in cytoplasmic
      ultrastructure.

PMID- 8268045
TI  - Comparison of the effects of various lengths of synthetic human parathyroid
      hormone-related peptide (hPTHrP) of malignancy on bone resorption and formation
      in organ culture.
AB  - Parathyroid hormone-related peptide (PTHrP) has been shown to be the pathogenic
      agent in humoral hypercalcemia of malignancy (HHM), but the molecular forms that
      are secreted have not been fully characterized. PTHrP 1-34 has effects similar to
      parathyroid hormone (PTH), but C-terminal regions of the peptide, such as the 107
      139 fragment found to inhibit resorption in a study by Fenton et al (1991), may
      have other biological activities not shared with PTH. We have compared the
      effects of the longer forms of recombinant human PTHrP (hPTHrP 1-84, 1-108, and 1
      141) with hPTHrP 1-34 and synthetic bovine PTH (bPTH) 1-34 on bone resorption and
      formation in cultured neonatal mouse calvariae and fetal rat long bones. hPTHrP 1
      84, 1-108, and 1-141 were qualitatively similar to hPTHrP 1-34 and PTH 1-34 in
      stimulating 45Ca release from both neonatal mouse calvariae and fetal rat long
      bones and in inhibiting the incorporation of [3H]-proline into collagenase
      digestible protein (CDP) and stimulating the incorporation of [3H]-thymidine (3H
      TdR) in neonatal mouse calvariae. However, hPTHrP 1-108 and 1-141 were less
      potent at stimulating 45Ca release and inhibiting CDP labeling than hPTHrP 1-34,
      while hPTHrP 1-84 showed an intermediate potency. Since hPTHrP 1-108 and 1-141
      were quite similar in potency, the difference cannot be attributed to an
      inhibitory effect of the 107-139 fragment. All the peptide lengths tested showed
      similar potency in stimulating [3H]-TdR incorporation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268046
TI  - Fluoride increases rat osteoblast function and population after in vivo
      administration but not after in vitro exposure.
AB  - The effects of fluoride on bone tissue are now well documented by in vivo
      histological studies performed on both human and animal bone biopsies and
      demonstrating an increase in osteoblast (OB) population. In order to elucidate
      whether the mechanism of action of fluoride on osteoblasts was direct or
      indirect, 14 three-week-old Sprague-Dawley rats were selected. Seven animals
      received 100 ppm fluoride as sodium fluoride (NaF) in drinking water for one
      month. The other animals, which did not receive fluoride, were considered as
      controls. At the end of the experiment, femurs and vertebrae were excised and
      osteoblastic cells were obtained after collagenase digestion separately from each
      animal. The osteoblastic cells derived from control and NaF-treated rats were
      exposed in vitro to 10(-5) M NaF. Alkaline phosphatase (AP) activity was
      measured, and the cellular proliferation was assessed by 3H-thymidine
      incorporation. Thymidine incorporation and AP activity were significantly higher
      in osteoblastic cells derived from NaF-treated rats than in cells obtained from
      control rats (p = 0.05 and p < 0.01, respectively). In contrast, the osteoblast
      proliferation and activity were not modified after in vitro exposure to NaF in
      cells derived from control and NaF-treated rats. In conclusion, the function of
      osteoblasts was not modified after in vitro exposure to fluoride. In contrast,
      given in vivo to rats for one month, fluoride has a mitogenic effect on
      osteoblasts and stimulates their activity. These data emphasize the hypothesis
      that fluoride may act either on osteoprogenitor cells or through an indirect
      mechanism mediated by a cofactor.

PMID- 8268047
TI  - The renal response to exogenous parathyroid hormone in treated
      pseudohypoparathyroidism.
AB  - Resistance to the renal actions of parathyroid hormone (PTH) in
      pseudohypoparathyroidism (PsH) may be improved after treatment with vitamin D or
      its metabolites, but reports conflict. We have examined the renal response to
      infusion of 35 micrograms of 1-38 PTH in patients with PsH type I (n = 8) and PsH
      type II (n = 1) during treatment and related this to prevailing endogenous serum
      PTH and calcium levels. Nine patients with postsurgical or idiopathic
      hypoparathyroidism (HP) served as controls. The urinary cAMP increase (delta
      cAMP) was lower (p < 0.001) in the PsH type I (175 +/- 6.4 nmol/l glomerular
      filtrate) than in the HP group (3251 +/- 515 nmol/l glomerular filtrate). delta
      cAMP in the PsH type I subjects was dependent on endogenous PTH concentrations (r
      = -0.76; p = 0.046) and serum calcium (r = 0.74; p = 0.037). Phosphaturic
      responses (expressed as % decrease in TmPO4/glomerular filtration rate) were
      lower (p = 0.013) in the PsH type I (28.8 +/- 3.75) compared with those of the HP
      patients (43 +/- 3.48). The phosphaturic responses in the PsH type I patients
      were strongly dependent on endogenous PTH (r = 0.94; p < 0.001) and serum calcium
      levels (r = 0.94; p < 0.001) so that the responses of subjects with normal or low
      PTH levels were no different (p = 0.16) from the HP group. Renal handling of
      calcium and sodium in response to exogenous PTH was identical in patients with
      PsH (types I and II) and HP. Renal tubular reabsorption during a calcium infusion
      was normal in all patients with PsH. These results emphasise the importance of
      the modulatory effects due to associated biochemical abnormalities in PsH on the
      responses to exogenous PTH. They also confirm that renal handling of calcium and
      sodium is probably normal in treated PsH.

PMID- 8268048
TI  - Mechanical properties of osteopenic vertebral bodies monitored by acoustic
      emission.
AB  - A microdamage event, either bone microfracture or microcrack propagation,
      releases energy. Some of this energy is in the form of acoustic waves. We
      measured acoustic emission (AE) in normal and osteopenic vertebral bodies during
      compression loading to confirm the microdamage accumulation. The 2nd to 4th
      lumbar vertebrae taken from the embalmed cadavers of a 37-year-old male and a 75
      year-old female were used. Bone mineral densities (BMDs) were measured by dual
      energy X-ray absorptiometer (DEXA). The male vertebrae had normal BMDs, while the
      female vertebrae had lower BMDs than the normal range and were graded osteopenic.
      Mechanical parameters (maximum load, maximum stress, stiffness, strain at maximum
      load, and apparent elastic modulus) and AE event count rates in the load
      deformation curve were measured during quasi-static compression loading
      (deformation rate 0.1 mm/min). For all mechanical parameters, the normal
      vertebrae had higher values than the osteopenic vertebrae. Cumulative AE event
      counts until maximum load of the osteopenic vertebrae were much greater than that
      of normal vertebrae. The vertebrae which were well compressed to the plastic
      range in the load-deformation curve displayed dome-shaped fracture lines just
      above the end plates. These results are consistent with the hypotheses that
      microcracks of osteopenic vertebral bodies are generated and accumulate at lower
      strains than those of normal vertebrae at a specific site.

PMID- 8268049
TI  - Femoral head necrosis and osteopenia in stroke-prone spontaneously hypertensive
      rats (SHRSPs).
AB  - Necrosis of the femoral head and osteopenia were examined histopathologically in
      stroke-prone spontaneously hypertensive rats (SHRSPs) aged 6 to 36 weeks and
      compared with that of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto
      rats (WKYs). Avascular necrosis of the femoral head was frequently observed,
      mainly in the young SHRSPs and SHRs (about 8 to 15 weeks of age). SHRSPs had the
      highest incidence of femoral head necrosis among the three strains. This necrotic
      change in the femoral head was considered to be secondary ischemia induced by
      angiospasm or arteriosclerosis, similar to the disorders observed in the brain,
      kidney, and heart in SHRSPs. However, the complication occurred in spite of
      treatment with antihypertensive agents (ACE inhibitor: enalapril, spirapril) even
      though other ischemic disorders such as brain hemorrhage and renal infarction
      were prevented, indicating that the femoral head necrosis in SHRSPs was not due
      to hypertensive complications induced by angiospasm or arteriosclerosis. Bone
      mineral density (BMD) of the femoral bone was significantly lower in SHRSPs, and
      the femoral heads in this strain were the most easily deformed by loads applied
      during compression tests. Histopathologically, the infarctions were encountered
      on the lateral side of the epiphysis, but no thrombi were observed. The lateral
      side of the epiphysis is the anatomic site where the weight load is greatest and
      the site where the nutritive artery enters. Our results strongly suggest that the
      coexistence of vulnerable bone matrix and physical weight load to the nutritive
      artery plays a crucial role in the occurrence of femoral head necrosis in SHRSPs,
      whether based on generalized or localized osteopenia.

PMID- 8268050
TI  - Primary hyperparathyroidism: iliac crest cortical thickness, structure, and
      remodeling evaluated by histomorphometric methods.
AB  - Iliac crest bone biopsies from 62 patients (42 women, 20 men; median age 59
      years; range 17-79 years) with primary hyperparathyroidism (PHP) were examined.
      Static and structural parameters were compared with 30 age- and sex-matched
      normal controls. Eighteen sex-matched younger controls were used for evaluation
      of the dynamic controls. On the endocortical surface increase in extension of
      eroded (p < 0.01) and formative (p < 0.01) surfaces was found in PHPs compared
      with normals. Endocortical bone formation rate was increased in PHPs (p < 0.05),
      but mineral appositional rate and adjusted appositional rate were normal. On the
      periosteal surface very little remodeling activity was found. Although bone
      formation rate was found increased in PHPs (p < 0.05), more than half of the
      labeled biopsies were without periosteal tetracycline in patients, and only 2 of
      18 biopsies from normals contained periosteal tetracycline labels. No significant
      decreases in cortical width or relative cortical width were found in PHPs. In
      both patients and controls an age-related decrease in relative cortical width
      cortical width were found in PHPs. In both patients and controls an age-related
      decrease in relative cortical width was noted for women (PHPs: r = -0.52, p <
      0.01; controls: r = -0.59, p < 0.001), but not for men. Cortical porosity was
      about 30% increased in PHPs (p < 0.02). Only normal women showed a positive age
      related increase in porosity (r = 0.61, p < 0.05).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268051
TI  - Cortical aging differences and fracture implications for the human femoral neck.
AB  - Clinical imaging techniques cannot consistently identify individuals at risk for
      hip fracture. Individual differences in falling likelihood partly account for
      these inconsistencies, but it is also thought that microscopic bone changes may
      play a role. In this study, subcapital, mid-neck, and trochanteric sites from
      eight young adult (26 +/- 7 years) and nine older (63 +/- 3 years) males were
      studied using backscattered electron imaging to identify age-related microscopic
      structural and mineral changes around the cortex. Cortical bone volume
      (BV(Ct)/TV), cortical void volume (Vd.V(Ct)/TV), hypermineralized bone volume
      (BV(H-min)/TV), the number of osteons/mm2 (N.On/B.Ar), lacunae/mm2
      (N.Lc/B.Ar(Ct)) in the cortex, lacunae/mm2 (N.Lc/B.Ar(H-min)) in the
      hypermineralized phase, and cortical thickness (Ct.Th) were measured at
      subcapital, mid-neck, and trochanteric levels. Cortical void volume showed no
      differences (P = 0.26) between levels in the younger group, but differences (P <
      0.05) were observed in the older group, indicating locational osteopenic
      differences. Cortical thickness differences were greater at the subcapital
      (27.7%) and mid-neck (25.2%) levels than at the trochanteric level (10.5%). Both
      age (P = 0.0022) and level-location interaction (P < 0.0001) influenced the
      hypermineralized bone volume present, with larger hypermineralized regions
      generally occurring at the thinner superior locations. Significant (P < 0.05)
      lacunar differences with aging in the hypermineralized phase suggest a necrotic
      origin. Artifactual cracks occurred preferentially within the hypermineralized
      phase, indicating localized reductions in fracture toughness, which may provide a
      site for crack initiation following an impact.

PMID- 8268052
TI  - Toxic effects of Solanum malacoxylon on sheep bone.
AB  - Solanum malacoxylon (Sm), a calcinogenic plant that contains 1,25-(OH)2D3
      glycoside, was administered orally to sheep. Fifty milligrams of air-dried leaves
      three times a week caused an increased volume density of cancellous bone within
      lumbar vertebrae and an increased trabecular thickness. There was little
      remodeling activity at the end of a 180-day treatment period, and few trabecular
      bone surfaces had tetracycline double labels at this time. Bone biopsies taken at
      the end of a 1-month treatment demonstrated increased extent of bone-forming
      surfaces and osteoid volume. Sm caused a mineralization defect that was
      transitory but resulted in unmineralized lines and foci in osteones. These
      remaining foci of unmineralized bone were associated with the deposition of acid
      mucopolysaccharide, and acid mucopolysaccharide accumulation could be identified
      on all bone envelopes in 30-day biopsy specimens. A similar hyperostosis in the
      metaphyses of rats was produced by parenteral administration of 1,25-(OH)2D3 for
      10 days.

PMID- 8268053
TI  - Culture of marrow stromal cells derived from bone marrow specimens formed at
      fracture site of human long bone.
AB  - To study the process of the internal callus formation, we cultivated marrow
      stromal cells derived from bone marrow specimens formed at fracture sites of
      human long bone in alpha-modified Eagle's medium containing 10% fetal calf serum.
      After 2 weeks of culture, the cells formed two types of colonies; one consisted
      of spindle cells, and the other comprised of polygonal cells. The two types of
      colonies were separated and cultured further. The spindle and polygonal cells
      proliferated to confluence within 3 weeks and after 4 weeks, respectively, after
      the separation. Both the spindle and polygonal cells showed on the plasma
      membrane moderate intensity of staining reaction of alkaline phosphatase (ALPase)
      activity before the period of confluence and strong intensity during the period
      of confluence. Then, the spindle cells did not produce calcified matrix, but
      detached from the dish after 6-8 weeks of culture. In the colonies of polygonal
      cells, however, dense nodules were formed after 9 weeks of culture, which became
      visible to the naked eye as white aggregates after 11-12 weeks. Electron
      microscopic studies on the polygonal cells demonstrated matrix vesicles in the
      intercellular ground substance after 6 weeks of culture, and electron-dense
      needle-like crystals on the matrix vesicles after 8-10 weeks of culture. On the
      basis of infrared spectroscopic analysis, the aggregates were composed of
      hydroxyapatite. Thus, stromal cells derived from bone marrow specimens formed at
      fracture site of human long bone differentiated to spindle and polygonal cells
      containing high ALPase activity (a marker for osteogenic capacity) during
      culture, and the polygonal cells but not spindle cells produced the calcified
      matrix.

PMID- 8268054
TI  - Assessment of cleaning and disinfection in the food industry with the rapid ATP
      bioluminescence technique combined with the tissue fluid contamination test and a
      conventional microbiological method.
AB  - A quantitative ATP bioluminescence procedure has been used to determine the
      cleanliness of food processing factories and the results have been compared with
      those from conventional microbiological culture methods. ATP measurements were
      combined with the tissue or tissue fluid contamination (TTFC) assessment method
      to obtain an impression of the amount of inanimate contamination on the sampled
      surfaces. It was found that, in the sampled food factories, there was poor
      relation between the two assessment techniques: ATP bio-luminescence combined
      with TTFC and contact plating. However, either method in its own right is useful
      to check cleanliness of food industries. ATP measurements do have in addition the
      great advantage that it is a fast method and is easy to perform.

PMID- 8268055
TI  - Distribution of mesophilic Aeromonas species in raw and ready-to-eat fish and
      meat products in Switzerland.
AB  - A total of 829 poultry, meat, shellfish and fish products commonly consumed in
      Switzerland were qualitatively and quantitatively examined for the presence of
      mesophilic Aeromonas spp. Overall, aeromonads occurred in 24.1% of the samples.
      Raw food products were frequently contaminated (e.g. 94.1% in minced meat), with
      colony counts up to 6.0 x 10(6)/g. Some ready-to-eat products had a relatively
      high percentage of positive samples as well, such as cooked ham in slices
      (38.2%), mortadella (12.9%), smoked cooked sausage (15.6%), hot and cold smoked
      fish (10.9-14.3%) and gravad salmon (10.5%). Colony counts, however, were
      somewhat lower (up to 1.7 x 10(3)/g). The high contamination rate of cooked or
      hot smoked foods suggests recontamination after cooking or smoking, e.g., at the
      slicing and packaging stage. 61.2% of the identified strains were Aeromonas
      hydrophila, followed by 22.5% Aeromonas caviae and 16.3% Aeromonas sobria.

PMID- 8268056
TI  - Specific solute effects on Staphylococcus aureus cells subjected to reduced water
      activity.
AB  - The behaviour of Staphylococcus aureus cells subjected to lowered water activity
      (aw) by the addition of various solutes was examined by transmission electron
      microscopy. Solutes included sodium chloride, sucrose, propylene glycol, butylene
      glycol and various polyethylene glycols. Changes in other physical properties of
      the liquid growth medium brought about by the solutes were estimated
      theoretically. They did not correlate with the bacterial biological response. The
      inhibitory effects of sucrose and sodium chloride against S. aureus were
      primarily ascribed to their water activity-lowering abilities, showing no
      significant specific solute effects. However, the other solutes examined showed
      specific antibacterial activity against S. aureus which may be compatible with
      cell wall attack.

PMID- 8268057
TI  - Contamination of beef carcasses by psychrotrophic Pseudomonas and
      Enterobacteriaceae at different stages along the processing line.
AB  - The extent of the contamination of beef carcasses with psychrotrophic Pseudomonas
      spp. and Enterobacteriaceae during slaughter, chilling and cutting was estimated
      by introducing a new analytical procedure; the contamination index. Comparisons
      were made between the initial viable counts and the contamination index. The
      contamination index was calculated as the sum of the bacterial counts obtained
      during aerobic cold storage of excised meat samples. The presence and composition
      of spoilage bacteria in the slaughter environment and on the carcasses was also
      determined at one plant. Rapid chilling was identified as a critical processing
      step by the contamination index. In addition to this, the dehiding and the
      chilling in cold storage rooms were implicated as critical operations, with
      respect to aerosol contamination and surface cross-contamination. Comparison of
      the composition of spoilage bacteria in the slaughter environment and the
      bacteria proliferating on the carcass surface samples taken at the corresponding
      steps showed similar distributions of the identified Pseudomonas spp. In five
      surveys at two plants, the contamination of beef carcasses along the processing
      line was estimated. Statistically significant variations between different
      processing steps were more pronounced for the contamination index than for the
      conventional counts. It was concluded that the contamination index could be used
      for identifying critical processing steps, with respect to the extent of
      contamination of carcasses by psychrotrophic spoilage bacteria.

PMID- 8268058
TI  - Heat resistance of Listeria monocytogenes in vacuum packaged pasteurized fish
      fillets.
AB  - The heat resistance of two strains of Listeria monocytogenes in sous-vide cooked
      fillets of cod and salmon was investigated. Fish sticks of 5 g were inoculated,
      vacuum-packed and heated at different combinations of time and temperature (58-80
      degrees C). Time-temperature combinations allowing survival and time-temperature
      combinations at which the bacteria were destroyed, were used to determine D- and
      z-values. D-values were in the range of what has been published for other food
      products. D60-values were between 1.95 and 4.48 min depending on the strain and
      the fish. Both strains were one-four-times more heat resistant in salmon than in
      cod, showing the importance of the heating menstruum. This difference may be due
      to the higher fat content in salmon as compared to cod. Z-values were calculated
      to be 5.65 and 6.4 degrees C, respectively, for the two strains. The suitability
      of methods for heat resistance experiments and the survival of L. monocytogenes
      in sous-vide cooked fish fillets are discussed.

PMID- 8268059
TI  - The effects of modified atmospheres on the growth of psychrotrophic pseudomonads
      on a surface in a model system.
AB  - Atmospheres containing concentrations of CO2 as low as 20% (balance nitrogen)
      inhibited the growth of Pseudomonas fluorescens and Pseudomonas putida on the
      surface of buffered Brain Heart Infusion agar plates, pH 6.8, incubated at 5 or
      15 degrees C in flexible packages. The modified atmospheres decreased the growth
      rates and reduced the populations attained at the end of the exponential phase of
      growth, but had no substantial effect on the lag phase. P. fluorescens was less
      tolerant of CO2 than P. putida. The inhibitory effect of CO2 increased with its
      concentration and inhibition was greater at 5 than at 15 degrees C. Growth
      occurred in packages flushed with 20, 40 and 100% CO2 and 100% N2 at 15 degrees C
      and 20 and 40% CO2 and 100% N2 at 5 degrees C. The residual O2 concentration in
      the packages after flushing was 0.2-0.5%. Storage of pseudomonads in CO2 under
      conditions that prevented growth (e.g., 100% CO2, 5 degrees C) did not cause
      substantial loss of viability. There was no detectable residual effect of CO2. If
      cultures were incubated in air after storage for up to 70 days in CO2-containing
      atmospheres which prevented growth, the subsequent growth curve did not differ
      noticeably from that observed when plates were incubated in air immediately after
      inoculation. When cultures in the exponential or stationary phases of growth in
      modified atmospheres were transferred to air, growth rates increased quickly to
      rates similar to those observed in air and the final populations observed in air
      were attained. A reduction in the pH of the medium to 5.5 substantially increased
      the inhibitory effect of CO2. At 5 degrees C and pH 5.5, substantial growth of P.
      fluorescens was not observed in any of the CO2 concentrations tested, nor in 40
      or 100% CO2 for P. putida.

PMID- 8268060
TI  - In vivo 19F NMR studies of hyperthermia: hydrophobic environments probed by
      halothane.
AB  - The steady-state distribution of the general anesthetic halothane in different
      rat tissues, including a renal adenocarcinoma with and without hyperthermia
      treatment, has been evaluated by in vivo 19F NMR spectroscopy. The 19F spectra of
      halothane (which is a hydrophobic probe) from within tissue show differences in
      the partitioning between normal rat tissues and adenocarcinoma. Muscle, as a
      control tissue, exhibits a single large resonance around 0 ppm. However, the
      adenocarcinoma exhibits two slow-exchanging resonances separated by 0.3 ppm with
      the one at the more hydrophobic chemical shift being more sensitive to
      hyperthermia treatment. The results from this tumor model suggest that 19F NMR
      spectroscopy may be useful first in detecting a change in hydrophobic
      environments using a lipophilic probe such as halothane, and secondly in
      monitoring the effects of hyperthermia, a treatment whose effectiveness may
      involve changes at the level of the plasma membrane. Under conditions of
      continuous delivery, a resonance which is not detected in the spectra of
      halothane in excised tissue appears 5 ppm downfield from the resonance for
      halothane localized in tissues. A rotating frame experiment is used to show that
      this resonance is derived from anesthetic absorbed on the tissue surface.

PMID- 8268061
TI  - Growth and magnetic resonance characteristics of human squamous cell carcinoma
      xenografts implanted with cells suspended in Matrigel.
AB  - Growth and magnetic resonance characteristics of a human squamous cell carcinoma
      SQ20B were studied in vivo as xenografts in nu/nu nude mice. Tumor cells injected
      subcutaneously in the flank using either Matrigel (MTG, an extract of basement
      membrane proteins) or growth medium (GM) as a vehicle were compared. Much higher
      tumor growth rates and cell density were observed with Matrigel than with GM
      implantation. Histology also showed that MTG implanted cells grew as vascularized
      solid tumors compared to GM tumors which formed cysts. As a result of increased
      cell density with the improved method, tumors as small as 0.3 cm3 provide high
      S/N magnetic resonance spectra which yield smaller standard deviations with fewer
      experiments.

PMID- 8268062
TI  - Quantitative analysis by 31P magnetic resonance spectroscopy of abnormal
      mitochondrial oxidation in skeletal muscle during recovery from exercise.
AB  - We use the hyperbolic relationship between cytosolic [ADP] and the rate of
      phosphocreatine (PCr) resynthesis after exercise to estimate the apparent maximum
      rate of oxidative ATP synthesis (QMAX). We examine data from some human diseases
      in which mitochondrial oxidation may be impaired (due to reduced mitochondrial
      numbers, intrinsic mitochondrial defect or impaired vascular supply). Muscle
      responds to impaired oxidation by stimulating anaerobic ATP synthesis and/or by
      increasing [ADP], the stimulus to the mitochondrion. However, these responses
      interact: [ADP] depends on pH and [PCr], and lactic acid production tends to
      lower [ADP] (by lowering pH), while proton efflux has the opposite effect. We
      identify four patterns of results: (A) in mitochondrial myopathy, apparent QMAX
      is reduced and [ADP] is appropriately increased, because increased proton efflux
      reduces the pH change in exercise despite increased lactic acid production; (B)
      in some conditions (e.g., cyanotic congenital heart disease) apparent QMAX is
      reduced but there is no compensatory rise in [ADP], probably because anaerobic
      ATP synthesis during exercise is increased without increase in proton efflux; (C)
      in other conditions (e.g., myotonic dystrophy) [ADP] is increased during exercise
      but apparent QMAX is normal, suggesting either an increase in proton efflux
      and/or decrease in anaerobic ATP synthesis during exercise; (D) there are also
      conditions (e.g., respiratory failure) where, despite impaired oxygen supply,
      both apparent QMAX and end-exercise [ADP] are normal. We also discuss the
      metabolic conditions under which end-exercise [ADP] is increased by a
      mitochondrial defect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268063
TI  - Mapping of cerebral metabolites in rats by 1H magnetic resonance spectroscopic
      imaging. Distribution of metabolites in normal brain and postmortem changes.
AB  - The goal of this study was to examine metabolic differences between cortex and
      basal ganglia in normal rat brain and to determine postmortem changes using in
      vivo 1H magnetic resonance spectroscopic imaging at 300 MHz. The resonances
      observed were: choline, creatine + phosphocreatine, N-acetyl aspartate (NAA),
      lactate (Lac), and three small resonances in the amino acid region which included
      resonances from aspartate + NAA (Asp), glutamine + NAA (Gln), and glutamate +
      GABA (Glu). A previously unassigned resonance was observed at 1.13 ppm in brain
      of rats anesthetized with pentobarbital. Spectroscopic images in normal brain
      demonstrated increased NAA and Gln and decreased Glu in cortex compared to basal
      ganglia. The major postmortem changes were an increase of Lac, Glu and Cho and a
      decrease of NAA and Asp. The rise in Lac was significantly higher in cortex than
      in basal ganglia.

PMID- 8268064
TI  - Phospholipid metabolites, prognosis and proliferation in human breast carcinoma.
AB  - The content of the phospholipid metabolites, phosphocholine, phosphoethanolamine,
      glycerophosphorylcholine and glycerophosphorylethanolamine was measured in
      chemical extracts from 46 human breast carcinoma using 31P NMR spectroscopy. Some
      patients had received therapy prior to tumour resection. The data were therefore
      stratified into two groups: (i) all tumours; and (ii) untreated tumours. Three
      indices of tumour proliferation i.e., mitotic index, Ki67 and S-phase fraction
      were determined on tissue from the same tumours and were found not to correlate
      with the content of any of these metabolites. In addition oestrogen-receptor
      status and density, tumour grade and DNA ploidy were obtained on some tumours.
      The phosphocholine content was higher in high grade tumours when compared with
      low grade tumours. There was no apparent relationship between DNA ploidy and the
      content of any of these metabolites. Glycerophosphorylcholine content of
      oestrogen-receptor positive tumours correlated with receptor density. However,
      there was no significant difference between receptor positive and negative
      tumours in the content of any of the phospholipid metabolites measured.

PMID- 8268065
TI  - Differential diagnosis of solid renal tumors by MRI. Comparison of in situ
      relaxation times measured with a 0.1 T imager and histological findings.
AB  - The T1 and T2 of kidneys in 5 normal volunteers and 27 patients with renal tumors
      were evaluated preoperatively using a magnetic resonance imager with a 0.1 T
      resistive electromagnet, and the T1 and T2 of the renal tumors were compared with
      the pathological findings: (i) the T1 and T2 of the normal renal medulla were
      longer than those of the normal renal cortex and psoas muscle; (ii) both T1 and
      T2 of renal pelvic cancer (RPC) were shorter than those of renal cell cancer
      (RCC, p < 0.05); (iii) the T2 values of RPC were significantly shorter than those
      of renal medulla (p < 0.01); (iv) the T1 and T2 of the normal renal cortex of
      subjects < 50 years old were shorter than those of subjects > or = 50 years old
      (p < 0.05 and p < 0.01, respectively). These findings suggest that preoperative
      evaluation of the pathological findings of renal tumors may be possible by
      calculating the relaxation time using MRI under low magnetic field.

PMID- 8268066
TI  - Effect of hypoxia on bicuculline seizures of rat: NMR spectroscopy and
      bioluminescence imaging.
AB  - Previous studies suggested that hypoxia reduces the severity of brain injury
      after epileptic seizures. To test this hypothesis, the effect of hypoxic arrest
      of epileptic seizures on brain metabolism was investigated in rats by combining
      in vivo NMR spectroscopy with imaging techniques for the pictorial evaluation of
      energy metabolism and pH. Seizures were produced by i.v. injection of
      bicuculline, and measurements were compared in animals with and without 5 min
      exposure to 5% oxygen after the onset of seizures. Transient hypoxia persistently
      reduced seizure activity, even after return to normoxia. Hypoxia or seizure alone
      had little effect on brain metabolism but the combination of both led to marked
      albeit reversible deterioration of energy and acid/base status. In normoxic
      animals pictorial measurements of energy state 2 h after the onset of seizures
      revealed a regional decline of ATP in the hippocampus. In animals in which
      seizures were arrested by transient hypoxia ATP depletion was additionally
      observed in the border zones of vascular territories. These results demonstrate
      that hypoxic arrest of seizure activity leads to the aggravation of metabolic
      disturbances and is therefore not suited to preventing permanent brain injury.

PMID- 8268067
TI  - Diffusion into rat brain of contrast and shift reagents for magnetic resonance
      imaging and spectroscopy.
AB  - A sensitive radiotracer technique was used to measure transfer constants (Kis)
      for blood to brain diffusion of the MR contrast reagent gadolinium
      diethylenetriaminepentaacetate (GdDTPA2-) and the MR shift reagent dysprosium
      triethylenetetraminehexaacetate (DyTTHA3-) across the normal and the ischemically
      injured blood-brain barrier (BBB) of rats. In rats with a normal BBB mean Kis
      (nL/g/s) for these reagents ranged from 0.3 to 1.4 across eight brain regions and
      were significantly lower in each region than Kis for sucrose (1.5-3.2), a
      substance known to be a poor permeant of the intact BBB. Kis measured 6 h after a
      10 min period of normothermic forebrain ischemia were increased to 4.0-6.2
      (reagents) and 6.6-7.5 (sucrose) in two brain regions, striatum and hippocampus,
      known to be especially vulnerable to ischemic injury. Measurements of BBB
      permeability to DyTTHA3- after osmotic opening of the barrier with hypertonic
      arabinose gave Kis of 25-30 in forebrain regions. Estimates of reagent
      concentrations in brain interstitial fluid 30 min after dosing the animals
      indicated that both an extremely high dose of DyTTHA3- and severe disruption of
      the BBB would be required to shift the resonance frequency of extracellular Na+
      appreciably. With the moderate degrees of BBB injury produced by short-term
      ischemia, a dose of GdDTPA2- about 25 times the usual clinical dose of 0.1
      mmol/kg would be required to quantify the injury by dynamic MRI.

PMID- 8268068
TI  - Are both color-flow duplex scanning and cerebral arteriography required prior to
      carotid endarterectomy?
AB  - In an attempt to eliminate the morbidity, mortality, and cost associated with
      arteriography, surgeons are relying increasingly on duplex scanning of the
      extracranial arteries as the primary preoperative evaluation prior to carotid
      endarterectomy (CEA). This study was initiated to evaluate the need for cerebral
      arteriography in the preoperative evaluation of patients for CEA. One hundred
      five patients undergoing 114 CEA procedures are included in a retrospective
      review to determine whether the addition of cerebral arteriography changed the
      operative management of these patients. In 58 of 105 patients (55%), color-flow
      duplex scanning and cerebral arteriography were performed in the workup prior to
      CEA. In four patients a discrepancy was found between the duplex results and the
      arteriogram, leading to a change in the operative approach in two. The remaining
      47 patients (45%) underwent color-flow duplex scanning as the definitive
      preoperative study; the surgical management was altered because of the operative
      findings in one patient. Although color-flow duplex scanning does not provide
      absolute concordance with cerebral arteriography, in most instances it can be
      used as the definitive preoperative study prior to CEA. We define the indications
      for cerebral arteriography in patients undergoing CEA.

PMID- 8268069
TI  - Does routine patch angioplasty after carotid endarterectomy lessen the risk of
      perioperative stroke?
AB  - From 1964 through 1991 we performed primary closure of the arteriotomy in 1173
      patients and patch angioplasty in 506 patients after carotid endarterectomy. The
      decision to patch was made at the surgeon's discretion. In general a patch was
      used for small arteries. In the primary closure group 32 patients (2.7%) had a
      perioperative stroke and in the patch angioplasty group 17 (3.4%) had a stroke.
      The difference (2.7% vs. 3.4%) was not significant (p < 0.5275, Fisher's exact
      two-tailed test). A total of 240 arteries were closed with a vein patch and 11
      (4.6%) of these patients had a stroke; 266 were closed with a synthetic patch
      (Dacron, 211; polytetrafluoroethylene, 55) and six of the patients had a stroke
      (2.3%). The difference in stroke rate between the vein and synthetic patch groups
      (4.6% vs. 2.3%) was not significant (p < 0.2159). Patch angioplasty cannot be
      shown to reduce the incidence of perioperative stroke. Late carotid patency was
      not studied. This study supports a policy of selective patch angioplasty based on
      arterial size rather than patching all carotid arteries. When a patch is used, we
      prefer filamentous Dacron as the patch material.

PMID- 8268070
TI  - Endovascular obliteration of in situ saphenous vein arteriovenous fistulas during
      tibial bypass.
AB  - Current methods of ligating venous branches during in situ vein tibial bypass are
      associated with significant wound complications, especially in diabetics. Making
      only proximal and distal wound incisions could avoid these wound problems. We
      report the use of endovascular techniques with coils and balloons guided by
      intraoperative arteriography and angioscopy to obliterate arteriovenous (AV)
      fistulas in three elderly diabetic patients undergoing tibial bypass. In all
      cases the proximal and distal vessels were first isolated and deemed suitable for
      bypass. The greater saphenous vein was prepared for the proximal and distal
      anastomosis, and angioscopically guided valvulotomy was performed. An introducer
      sheath was placed through a large proximal saphenous side branch for vascular
      access. With the use of fluoroscopy, AV fistulas were serially identified and
      cannulated with a guidewire. A guide catheter, passed over the wire into the side
      branch, served as the conduit through which coils and balloons were placed.
      Proximal and distal anastomoses were completed and arteriography performed. We
      were successful in obliterating AV fistulas in all three patients, but completion
      arteriography revealed additional AV fistulas requiring surgical ligation in two
      patients. Furthermore, operative time was increased by 1 1/2 to 5 hours. Two of
      three patients had wound infections, one at the proximal and one at the distal
      incision. All patients were discharged with a functioning bypass and no AV
      fistulas were seen on duplex scans. Endovascular obliteration of AV fistulas is
      feasible but is currently limited by prolonged operative time and incomplete
      obliteration.

PMID- 8268071
TI  - Vascular access surgery as an outpatient procedure.
AB  - Construction of a vascular access site for hemodialysis has traditionally been
      done on an inpatient basis or more recently in a hospital operating room as a 1
      day admission. Over 18 months we performed 49 vascular access procedures on 45
      patients in a freestanding ambulatory surgical center. Four patients had an
      arteriovenous radiocephalic autogenous fistula constructed, 30 patients had a
      polytetrafluoroethylene (PTFE) prosthesis inserted as an arteriovenous bridge
      graft, 11 patients had a planned reconstruction of a previously placed graft, 1
      patient had a false aneurysm corrected, 1 patient had a chronically infected
      graft removed, and 2 patients had a thrombectomy. All procedures were in the
      upper extremities except for one femorosaphenous PTFE graft and one excision of a
      false aneurysm in a thigh prosthesis. Only one patient, an 84-year-old woman,
      required hospitalization following the outpatient procedure because she was
      unable to care for herself. No postoperative infection had occurred at 1 month
      follow-up. A left upper extremity graft performed at another inpatient facility
      was removed because of infection. The protocol for outpatient vascular access
      surgery includes preoperative evaluation of the patient for determination of the
      access site within a week of operation; duplex scan of subclavian veins if
      central venous lines have been in place for more than 2 weeks; scheduling surgery
      for the afternoon or morning following routine hemodialysis; obtaining a
      hemoglobin level, serum/electrolyte study, and an ECG following the last
      hemodialysis; parenteral antimicrobial prophylaxis; local infiltration anesthesia
      with standby; a minimum of 1 hour of observation in the recovery room; and a
      repeat hematocrit study prior to discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268072
TI  - The "blue-toe" syndrome as a harbinger of impending infrainguinal vein graft
      failure: a report of three cases.
AB  - Spontaneous "blue-toe" syndrome classically results from distal lower extremity
      microembolization of intraluminal atheromatous debris from a proximal source to
      the digital end arteries. During a 6-year period, 274 consecutive infrainguinal
      reversed vein arterial reconstructions were performed; in three patients (1.1%
      incidence), atypical distal microembolization originating from focal preocclusive
      intraluminal vein graft stenoses was identified. Sudden, spontaneous onset of
      ipsilateral blue-toe syndrome occurred at intervals of 4 to 11 months. Subsequent
      duplex scans and arteriography demonstrated patent grafts with high-grade,
      hemodynamically significant focal proximal short-segment sclerotic vein graft
      stenosis (n = 1) and midgraft valvular weblike stenoses (n = 2) with luminal
      irregularity. No other associated tandem lesions in the proximal or distal
      arterial tree were noted that would account for the microembolic phenomenon. The
      stenotic vein segments were excised with interposition vein graft replacement (n
      = 1) or with primary end-to-end reanastomoses (n = 2), resulting in complete
      resolution of the distal microembolic events without need for amputation.
      Histologic examination of these graft lesions demonstrated significant focal
      myointimal hyperplasia with adherent platelet aggregates and organized thrombus.
      The clinical presentation of distal lower extremity cutaneous digital ischemia
      consistent with microembolization developing ipsilateral to a previously placed
      vein conduit arterial bypass may signify a "failing" graft with a source from a
      preocclusive lesion. This finding should prompt aggressive evaluation and
      immediate revision to maintain assisted primary graft patency and prevention of
      tissue loss.

PMID- 8268073
TI  - Claudication in an adolescent with a hypoplastic femur.
AB  - The most common cause of claudication is atherosclerosis obliterans. However,
      when it presents in adolescence, other causes should be considered. We describe
      the case of a 15-year-old girl who had severe intermittent claudication 8 years
      after a limb-lengthening procedure for a hypoplastic femur. The lesion
      responsible was an isolated fibromuscular dysplastic segment of the distal
      superficial femoral artery and proximal popliteal artery. The etiology,
      treatment, and histopathology are discussed.

PMID- 8268074
TI  - Candida thrombosis of the innominate vein with septic pulmonary emboli.
AB  - Thrombosis of central veins has become more prevalent because of increased use of
      long-term central venous catheterization. Candida superinfection of the thrombus
      can occur particularly in patients on long-term antibiotic therapy and on
      parenteral nutrition. Removal of the catheter, thrombolytic therapy,
      anticoagulation, and antifungal therapy with amphotericin B will usually
      eradicate the candidemia and restore venous patency. Occasionally this
      therapeutic regimen fails. This case report illustrates such a failure in which
      multiple pulmonary emboli could have caused death. Surgical thrombectomy of the
      innominate vein effectively removed the source of the Candida sepsis and
      maintained patency of a major vein. Thrombectomy should be considered as a
      therapeutic option in septic central vein thrombosis.

PMID- 8268075
TI  - Aneurysm of the inferior vena cava: case report and review of the literature.
AB  - Aneurysms of the inferior vena cava (IVC) include a diverse group of anomalies
      with distinct anatomic and clinical characteristics. We report a diverticular
      aneurysm of the suprarenal IVC in a 45-year-old man who presented with extensive
      IVC and unilateral lower extremity thrombosis. A CT scan revealed an 8 cm smooth
      walled mass containing thrombus to the right of the IVC and behind the second
      portion of the duodenum. At laparotomy a connection between the mass and the
      suprarenal IVC was established. Biopsy of the wall of the mass revealed vascular
      smooth muscle, thus establishing the diagnosis of a diverticular IVC aneurysm. MR
      angiography further disclosed interruption of the infrahepatic vena cava and
      return of renal vein flow via the azygous and hemiazygous veins. Twelve
      additional cases of IVC aneurysm are reviewed. A proposed classification of these
      aneurysms into four types consistent with their anatomic and embryologic
      characteristics is presented.

PMID- 8268076
TI  - Intestinal ischemia secondary to thromboangiitis obliterans.
AB  - A 38-year-old woman presented with a 10-month history of postprandial abdominal
      pain and weight loss. She smoked two packs of cigarettes a day, but her history
      did not indicate diabetes mellitus, hyperlipidemia, or hypercoagulability. A
      lateral aortogram documented complete occlusion of all three mesenteric arteries
      but showed no evidence of atherosclerosis, arteritis, or medial fibroplasia. Two
      retrograde aortomesenteric grafts, one to the superior mesenteric artery and
      another to the meandering mesenteric artery, utilizing the greater saphenous vein
      were placed. Pathologic examination of the inferior mesenteric artery
      demonstrated changes that were considered diagnostic of thromboangiitis
      obliterans. We found only 10 confirmed cases of thromboangiitis obliterans
      involving the mesenteric vessels in the English language literature. The present
      case appears to be the first involving a woman and the only one in which the main
      trunk of all three mesenteric vessels was involved.

PMID- 8268077
TI  - Splenorenal bypass for right renal artery revascularization.
AB  - Splenic artery to right renal artery bypass was used successfully for surgical
      correction of renovascular hypertension in an elderly patient. The technique used
      is described.

PMID- 8268078
TI  - Aortic aneurysm rupture into a retroaortic left renal vein.
AB  - We report the case of a patient who was transferred to our facility after a CT
      scan obtained at a local hospital revealed a leaking abdominal aortic aneurysm.
      Review of the scan showed an aorto-left renal vein fistula. Knowing this fistula
      was present made the operative repair of the aneurysm and control of the fistula
      much more straightforward than might otherwise have been the case. Although
      relatively rare, major anomalies of the renal veins and perirenal vena cava
      should be borne in mind when operating on the abdominal aorta. This case
      illustrates the merit of contrast-enhanced CT scanning prior to aortic surgery.

PMID- 8268079
TI  - Posttraumatic innominate artery aneurysm with occlusion of the common carotid
      artery at its origin by an intimal flap.
AB  - Blunt trauma involving the innominate and carotid arteries is a rare occurrence
      that can be lethal or have serious neurologic sequelae. To our knowledge this is
      the first reported case in the international literature describing the
      association of posttraumatic innominate artery aneurysm with total occlusion and
      thrombosis of the common carotid artery at its origin by an intimal flap. The
      diagnostic problems created by this unusual injury are discussed. In this case
      the patency of the distal portion of the common and internal carotid arteries was
      demonstrated by magnetic resonance angiography (MRA), whereas color duplex and
      digital arteriographic studies were unsuccessful. This demonstration was crucial
      to patient management. Since no studies are available comparing color duplex
      imaging, conventional arteriography, and MRA in the evaluation of blunt carotid
      trauma, this case study is presented to demonstrate the utility of MRA in
      emergency situations. In addition, we analyze the possible pathogenesis and
      discuss the surgical treatment.

PMID- 8268080
TI  - Defecation syncope secondary to functional inferior vena caval obstruction during
      a Valsalva maneuver.
AB  - This report describes a case of defecation syncope secondary to functional
      inferior vena cava (IVC) obstruction. Preoperative hemodynamic assessment
      revealed a marked decrease in blood pressure and IVC obstruction when the patient
      performed a Valsalva maneuver. The intraoperative approach included continuous
      hemodynamic monitoring as well as transesophageal ultrasonography to assess IVC
      patency during surgical mobilization of the IVC. Functional obstruction of the
      IVC at the diaphragmatic hiatus was identified, and this obstruction was relieved
      with extensive mobilization of the IVC and right crural myotomy. This report
      describes an effective surgical approach to a rare functional disorder involving
      the IVC.

PMID- 8268081
TI  - Extra-anatomic bypass.

PMID- 8268082
TI  - Transobturator aorto-profunda femoral artery bypass using the direct medial thigh
      approach.
AB  - We present a novel technique for aorto-profunda femoral artery bypass using both
      the obturator foramen and the direct medial thigh approach to the profunda
      femoral artery in a patient with an infected femoral graft and limb-threatening
      ischemia. This patient has undergone multiple bypass grafts to salvage function
      of his lower extremities, but these standard anatomic and extra-anatomic bypasses
      had failed because of graft infections. The technique as well as the surgical
      anatomy are described. The combination of the transobturator aorto-profunda
      femoral artery bypass and the direct medial approach to the profunda femoral
      artery is technically feasible, provides adequate outflow for limb salvage in
      selected patients with good collateral arteries, offers acceptable long-term
      patency, and is particularly useful when the groin is hostile to dissection or
      graft material and the superficial femoral and popliteal arteries are occluded.

PMID- 8268083
TI  - The original vascular clamp.

PMID- 8268084
TI  - Risk factors for atherosclerotic aortoiliac occlusive disease.
AB  - Notwithstanding the difficulties in analysis because of the small number of
      studies available, patients with aortoiliac atherosclerosis, irrespective of
      their sex, have a particular "risk profile" that includes tobacco use, young age,
      diabetes (rare), frequent hypercholesterolemia, and limited atheroma. It must be
      remembered, however, that most studies have not dealt with the specific risk
      factors of lower limb arterial disease and the location of disease in the
      aortoiliac vessels. It is possible that the classical analysis of the vascular
      risk factors has overlooked one or more major factors such as
      hyperhomocysteinemia. This underscores the necessity to conduct further
      prospective studies specifically focused on the various aspects of lower limb and
      aortoiliac arterial disease in particular.

PMID- 8268085
TI  - Does carotid eversion endarterectomy and reimplantation reduce the risk of
      restenosis?
AB  - Two hundred twelve eversion endarterectomies of the internal carotid artery and
      reimplantation in the common carotid artery were performed between January 1985
      and July 1990. A total of 206 patients with stenosis of 75% or more and with
      redundancy and tortuosity of the internal carotid artery underwent this
      procedure. Cumulative mortality and neurologic morbidity were 2.4%. Forty
      patients died during the course of follow-up, seven of neurologic causes (17.1%).
      Duplex scans of 107 operated carotid arteries were obtained an average of 27.1
      months after surgery. Restenosis of > 50% was encountered in three patients
      (1.9%), two asymptomatic patients (1.3%) with > 75% restenosis and one
      symptomatic patient with occlusion (0.6%). These results contrast with a 13.5%
      rate of restenoses > 50% (including 5.9% of restenoses > 75% and 1.7% occlusions)
      observed after 156 consecutive endarterectomies performed and closed by direct
      suture by the same surgical team in 1987 at a mean follow-up of 44 months. We
      believe that this technique can be used more often because the the operative and
      long-term risks are not any greater than those of the other methods of carotid
      revascularization. Eversion endarterectomy associated with reimplantation is
      especially indicated when the internal carotid artery is elongated, is < 4 mm
      wide, and occurs in women.

PMID- 8268086
TI  - Spontaneous dissection of the abdominal aorta: experience with five patients.
AB  - Spontaneous dissection of the infradiaphragmatic abdominal aorta is a rare form
      of aortic dissection. Its natural history and management are not well defined. We
      have recently treated five patients with spontaneous aortic dissection. Two
      patients had acute dissections and three had chronic dissections. Three patients
      developed saccular aneurysms and underwent resection. Two patients had stable
      dissections and were treated medically. All patients are alive and well at 6
      months to 5 years. We think that spontaneous aortic dissection can be treated as
      a variant of type III dissection with initial medical management, reserving
      surgery for those patients in whom a saccular aneurysm or a complication of the
      dissection develops.

PMID- 8268087
TI  - Functional health and well-being in patients with severe atherosclerotic
      peripheral vascular occlusive disease.
AB  - Functional health and sense of well-being are known to be adversely affected by
      chronic illness. The extent to which peripheral vascular occlusive disease (PVOD)
      alters these factors independent of other comorbid conditions is unknown. Sixty
      patients with PVOD severe enough to have required aortobifemoral bypass (AFB)
      between 1985 and 1990 were selected for evaluation. Although all were heavy
      smokers and 20% had suffered previous myocardial infarction, all had adequate
      cardiopulmonary function to survive AFB. The SF-20 questionnaire, validated in
      the Medical Outcomes Study (MOS), was used to evaluate patients' functional
      health and well-being at least 6 months after AFB. All grafts were patent at the
      time of questionnaire completion. Three measures of functional health (physical
      function, role function, and bodily pain) and three measures of well-being
      (mental health, health perception, and social function) were scored from SF-20
      responses using the MOS protocol. These PVOD patients were then compared to MOS
      norms for patients without any chronic disease, to MOS norms adjusted for age and
      other comorbidities of the PVOD patients sampled, and to patients with congestive
      heart failure or recent myocardial infarction. Physical function, role function,
      and health perception were worse and bodily pain greater in patients with severe
      PVOD after surgical treatment as compared with MOS patients even after adjustment
      for comorbidities. Decrements in physical function, role function, and health
      perception for PVOD patients were comparable to MOS patients with congestive
      heart failure or recent myocardial infarction, whereas level of bodily pain was
      worse in PVOD patients than in these other groups. After adjustment for
      comorbidities, social function and mental health were not independently affected
      by PVOD. Functional health and well-being were not significantly different when
      PVOD patients with limb threat were compared to those with claudication. Severe
      PVOD is associated with decrements in functional health and well-being comparable
      to or greater than other severe chronic illness, even after successful
      revascularization. Further study is needed to examine the effect of
      revascularization on functional health.

PMID- 8268088
TI  - Enhanced patency of venous Dacron grafts by endothelial cell sodding.
AB  - The effect of microvessel endothelial cell (EC) sodding on the patency of Dacron
      grafts interposed in canine inferior vena cava was studied. EC were harvested
      enzymatically from canine omentum and isolated by density gradient
      centrifugation. Preclotted, knitted Dacron grafts were sodded with > 10(6) EC/cm2
      surface. The results demonstrate significant improvement in patency of sodded
      grafts placed in the inferior vena cava as compared with control grafts (p <
      0.001 in grafts with a distal arteriovenous fistula and p < 0.05 in grafts
      without a distal fistula). The neointima of the sodded grafts were thinner and
      scanning electron microscopy confirmed the presence of a confluent layer of EC.
      In addition, the production of prostacyclin but not thromboxane A2 was
      significantly enhanced in the sodded grafts as compared with controls. We
      conclude that microvessel EC sodding of Dacron grafts significantly improves the
      patency rate and inhibits neointimal thickening of the prosthesis. The mechanism
      is unknown but may involve a more rapid endothelialization of the graft surface
      with the potential of producing more prostacyclin and less thromboxane A2.

PMID- 8268089
TI  - Operative transluminal laser angioplasty as the sole treatment for late stenoses
      of femorodistal artery bypass graft: experimental and clinical studies.
AB  - To determine the role of Nd:YAG laser thermal angioplasty as the sole treatment
      for late stenoses of femorodistal artery bypass graft, the lasing effect of a
      larger size of hot-tip probe (3, 4, and 5 mm) was experimentally studied in
      vitro. For an adequate lasing effect, 30 watts of laser power output for 3
      seconds was needed for the 3 mm probe, 40 watts for the 4 mm probe, and 50 watts
      for the 5 mm probe, respectively. Based on these results, we used Nd:YAG laser
      thermal angioplasty alone for 25 grafts, including 16 polytetrafluoroethylene
      (PTFE) grafts, eight saphenous vein grafts, and one externally supported (EXS)
      Dacron graft in which the stenotic lesions were detected by deterioration of the
      Doppler flow waveform pattern or a significant fall in the ankle/brachial
      pressure index (ABPI). Follow-up was from 3 to 24 months (average of 9 months)
      for PTFE grafts, from 5 to 21 months (average of 11 months) for saphenous vein
      grafts, and 13 months for the EXS Dacron graft following femorodistal artery
      reconstructions. Stenotic lesions were most common in the distal anastomotic
      sites: 11 PTFE grafts, three saphenous vein grafts, and one EXS Dacron graft.
      Among these, 13 grafts showed a type II flow waveform pattern at the time of
      surgery. Clinical success was achieved in 12 of the PTFE grafts (75%), in five of
      the vein grafts (62.5%), and in the single EXS Dacron graft. Four PTFE and three
      saphenous vein grafts failed subsequent to repeat intraoperative balloon
      angioplasty in three and graft extension in three and one graft
      interposition.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268090
TI  - Lipoprotein (a): a risk factor for peripheral vascular disease.
AB  - Lipoprotein (a) [Lp(a)] is a serum protein that has been reported to be
      predictive of complications from coronary and cerebrovascular atherosclerotic
      disease. This study was designed to compare plasma levels of Lp(a) in 100 white
      male patients with and without peripheral vascular disease (PVD) and to determine
      the role of Lp(a) as a risk factor for PVD independent of known risk factors such
      as cigarette smoking (CIG), diabetes mellitus (DM), and coronary artery disease
      (CAD). Patients with PVD (mean age = 67.6 years, n = 50) had a statistically
      significant (p = 0.04) elevation of Lp(a) (29.8 +/- 3.9 mg/dl) as compared to
      patients without PVD (20.0 +/- 2.9 mg/dl (mean age = 68.3 years, n = 50). Further
      analysis revealed that patients with PVD had a significantly higher incidence of
      CIG (86% vs. 68%, p = 0.03), DM (34% vs. 14%, p = 0.02), and CAD (52% vs. 30%, p
      = 0.02) than those without PVD. However, there was no statistically significant
      difference in Lp(a) levels in patients with CIG or CAD compared to those without.
      Patients with DM had significantly (p = 0.04) lower levels of Lp(a) (17.8 +/- 3.5
      mg/dl) than those without DM (27.1 +/- 3.0 mg/dl). Stepwise regression analysis
      of these various risk factors for PVD revealed that Lp(a) was the strongest
      significant individual predictor for the presence of PVD (R2 = 0.07) as compared
      to DM (R2 = 0.05) and CIG (R2 = 0.04). We conclude that there is a significant
      correlation of Lp(a) levels and the incidence of PVD, which is independent of
      other major risk factors for PVD.

PMID- 8268091
TI  - Surgical treatment of superior mesenteric artery dissecting aneurysm and
      simultaneous celiac artery compression.
AB  - Spontaneous dissections of visceral arteries are rare, but when they do occur,
      they most commonly involve the superior mesenteric artery (SMA). We present a
      case of intestinal ischemia caused by a spontaneous dissection of the SMA in a
      patient with simultaneous celiac artery occlusion. The patient was a 45-year-old
      woman who presented with intestinal angina of sudden onset. Arteriography
      revealed the classic findings of SMA dissection and occlusion of the celiac
      artery. The patient underwent repair of both visceral vessels and made a full
      recovery. The 18 previously reported cases of isolated, spontaneous dissection of
      the SMA are reviewed. No previous case has been associated with celiac
      compression syndrome. The reported experience with symptomatic dissections of the
      SMA would suggest that prompt surgical repair is indicated and yields excellent
      results.

PMID- 8268092
TI  - Spontaneous thrombolysis of native artery occlusions.
AB  - Acute arterial ischemia of the lower extremities is a major cause of mortality
      and limb loss in patients with peripheral vascular disease. Patients with acute
      limb ischemia secondary to embolus or in situ thrombosis usually require
      emergency revascularization, either surgically or with the use of thrombolytic
      agents. It is commonly assumed that heparin therapy alone, without
      disobliterative intervention, can produce clinical improvement through continued
      patency and enlargement of the collateral circulation. The occurrence of
      spontaneous thrombolysis of major limb vessels is not generally accepted. We
      describe three patients, all with confirmed occlusion of either the iliac or
      superficial femoral arteries, who had spontaneous thrombolysis of occluded
      vessels. These experiences document that spontaneous resolution of arterial
      occlusion does occur, although it may be infrequent.

PMID- 8268093
TI  - Blunt injuries to the innominate artery.
AB  - Two patients with aneurysm secondary to blunt traumatic subadventitial rupture of
      the distal innominate artery (IA) are reported. IA rupture was identified because
      of a cervical bruit in one patient and detected during thoracic aortography in
      the other patient. The patients had associated cardiovascular lesions consisting
      of traumatic aneurysm of the subclavian artery and rupture of the aortic valve,
      respectively. Both lesions were surgically repaired by resection of the lacerated
      intima and direct closure of the adventitia. In the patient who underwent repair
      of the aortic valve with simultaneous cardiopulmonary bypass the IA was
      approached after cannulation of the right common carotid artery. In the other
      patient the IA was repaired without use of a shunt under close EEG monitoring.
      Injury to the IA is rare because the artery is short and relatively well
      protected by the bony cage. Other cardiovascular lesions may be associated with
      IA rupture and a routine search should be made.

PMID- 8268094
TI  - Giant splenic artery aneurysm.
AB  - Giant aneurysms of the splenic artery are uncommon. The mean size of splenic
      artery aneurysms is reported to be 2.1 cm; they are rarely larger than 3 cm. We
      present two cases in which the splenic artery aneurysm was larger than 8 cm,
      discuss the management and operative approach to these infrequently encountered
      entities, and provide a brief review of the relevant literature.

PMID- 8268095
TI  - Posttraumatic arteriovenous fistula and subclavian vein thrombosis: treatment by
      percutaneous arterial embolization and vein angioplasty.
AB  - A 71-year-old woman had edema and venous dilatation of her upper right limb that
      caused painful functional disability following a shoulder injury. Arteriograms
      demonstrated an arteriovenous fistula between the subclavian artery and vein
      associated with thrombosis of the vein at the same level. The arteriovenous
      fistula was found to have multiple arteriovenous communications. Because of
      associated distal venous thrombosis, venous drainage was retrograde through the
      brachial vein. The inflow arteries of the fistula were embolized and then the
      subclavian vein thrombosis was recanalized, dilated, and an endoluminal stent
      inserted. Clinical signs completely resolved.

PMID- 8268096
TI  - Bilateral brachial artery fibromuscular dysplasia.
AB  - Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease
      that usually involves medium- and small-sized arteries. It is most commonly
      observed in the renal, carotid, and intracerebral arteries, although it has been
      reported in other arterial beds. The most common form is characterized by medial
      fibrosis, with or without smooth muscle cell hyperplasia, which can result in
      luminal narrowing and turbulent flow. There is often a secondary aneurysmal
      degeneration of the artery, which may or may not be associated with thrombosis or
      obstruction of flow. This accounts for the typical "string-of-beads" appearance
      seen on arteriography. We describe a patient who presented with ischemia of the
      right hand secondary to fibromuscular dysplasia of the brachial artery.
      Subsequent studies also demonstrated fibromuscular dysplasia in the other
      brachial artery as well as mild involvement of the right renal artery. The
      patient was treated on the symptomatic side with dilatation of proximal lesions,
      resection of the thrombosed segment, and reconstruction with a reversed saphenous
      vein graft. Distal pulses were fully restored postoperatively. Pathologic
      examination confirmed the arteriographic and clinical diagnosis of fibromuscular
      dysplasia. The salient features of this case are reviewed in addition to the
      other cases reported in the literature.

PMID- 8268097
TI  - Endothelial seeding of vascular prostheses: a technique of in situ enzymatic
      retrieval of endothelial cells without vein sacrifice.
AB  - The success of endothelial seeding of vascular prosthetic grafts is largely
      dependent on endothelial cell retrieval. An in situ cell harvesting technique
      using enzymatic dissolution in a temporarily excluded segment of the internal
      jugular vein is described. With this technique the cellular yield is adequate and
      the internal jugular vein remains patent. This technique allows for high-density
      seeding in a single stage. In two-stage seeding the excellent yield of cells
      reduces the duration of in vitro endothelial cell culture and allows for
      secondary massive and early seeding.

PMID- 8268098
TI  - Outcome criteria in patients with peripheral arterial disease.
AB  - To adequately evaluate patients with chronic occlusive arterial disease several
      factors will need to be taken into account and documented. These include
      associated diseases such as diabetes mellitus. When surgical or endovascular
      therapy is applied, analysis of outcome must include the symptomatic status of
      the patient, the anatomic evidence of patency of the procedure and of the
      proximal and distal disease, the hemodynamic result, limb preservation, and
      mortality. All of these factors will provide a better global picture of the
      disease and information on how it can be best treated.

PMID- 8268099
TI  - Vertebral artery reconstruction.

PMID- 8268100
TI  - Influenza in the world. 1 October 1992-30 September 1993.

PMID- 8268101
TI  - Global programme on AIDS. Sentinel HIV surveillance.

PMID- 8268102
TI  - American Association for Cancer Education 27th annual meeting. Houston, Texas,
      November 18-21, 1993. Program and abstracts.

PMID- 8268103
TI  - Maxon is an optimal suture for bile duct anastomoses in pigs.
AB  - BACKGROUND: Three commonly used sutures were tested in a pig model of bile duct
      anastomosis to assess their relative contributions to inflammation and scarring.
      METHODS: Thirty pigs were randomised to bile duct division and anastomosis with
      either polyglyconate (Maxon), polyglactin 910 (Vicryl) or polypropylene
      (Prolene). Half the animals were sacrificed at two weeks and the remainder at 23
      weeks. Anastomoses were assessed by cholangiography, scanning electron microscopy
      and light microscopy. RESULTS: There was less short term histological reaction
      with the two monofilament materials, Prolene and Maxon, compared to the braided
      suture Vicryl. Maxon was associated with less long term inflammation than
      Prolene, was found to handle better, and has an advantage over Prolene by being
      absorbable. CONCLUSION: Maxon is an optimal suture for bile duct anastomoses. Its
      long term absorption characteristics make it suitable for situations where bile
      duct healing may be delayed.

PMID- 8268104
TI  - Structure and innervation of the extrahepatic biliary system in the Australian
      possum, Trichosurus vulpecula.
AB  - The morphology, microanatomy and innervation of the biliary tree of the
      Australian possum, Trichosurus vulpecula, was examined. The gross morphology of
      the gallbladder, hepatic and cystic ducts, and the course of the common bile
      duct, conforms to those of other species. The sphincter of Oddi has an
      extraduodenal segment that extends 15mm from the duodenal wall; within this
      segment the pancreatic and common bile ducts are ensheathed together by sphincter
      muscle. Their lumens unite to form a common channel within the terminal
      intraduodenal segment. Nerve cell bodies of the gallbladder were found in an
      inter-connecting network of ganglia that were located in the serosa, muscularis
      and mucosa. Nerve fibres innervated the muscle, arterioles and the mucosa. Few
      ganglia were found along the supra sphincteric portion of the common bile duct.
      Nerve trunks followed the duct and a dense nerve fibre plexus was found in the
      mucosa. In the sphincter most ganglia were located in two plexuses, the first
      between the layers of the external sphincter muscle, which was continuous with
      the external muscle of the duodenum, and the second was associated with the
      internal sphincter muscle. Nerve fibres were numerous in the sphincter muscle,
      and were also found in the subepithelial and periglandular plexuses of both the
      pancreatic and common bile ducts.

PMID- 8268105
TI  - Successful arterial embolisation of giant liver haemangioma. Report of a case
      with five-year computed tomography follow-up.
AB  - A 28-year old man presented with a symptomatic giant haemangioma. On June 26,
      1983, at laparotomy, no resection was attempted because the lesion involved the
      right lobe of the liver and a part of segments II and III. The patient underwent
      a right hepatic arterial embolisation with gelatine sponge particles. During
      follow-up, the patient remained asymptomatic. Five-year review by CT-scan showed
      a diminution of the size of the haemangioma and hypertrophy of the left lobe. On
      October 21, 1988, the patient was reoperated on for liver abscess and complete
      necrosis of the haemangioma. A right hepatectomy was performed. In conclusion,
      the long-term effect of hepatic arterial embolisation, as demonstrated in our
      case by regular CT-scans, is useful in cases of diffuse haemangioma as an
      alternative to hazardous major liver resection. To our knowledge, the long-term
      effect of hepatic arterial embolisation on symptoms and tumor size have never
      been reported for giant liver haemangioma.

PMID- 8268106
TI  - Gallbladder volvulus.
AB  - A case of torsion of the gallbladder is presented. This is a rare condition that
      occurs more frequently in elderly females, it is associated with anatomical
      variants related to abnormal fixation of the gallbladder to the liver bed. It is
      usually diagnosed at laparotomy and treatment consists of cholecystectomy. This
      condition should be suspected in elderly females with acute cholecystitis or
      acute abdominal pain of unknown origin.

PMID- 8268107
TI  - Gastrointestinal hemorrhage due to splenic artery aneurysm pancreatic duct
      fistula in chronic pancreatitis. A case report and review of the literature.
AB  - Gastrointestinal hemorrhage due to splenic artery aneurysm pancreatic duct
      fistula in chronic pancreatitis is rare. It is, however, important to diagnose
      this condition particularly in patients having chronic pancreatitis, since it may
      result in a life-threatening situation. The diagnosis is usually difficult to
      establish and it may take repeated admissions for intermittent gastrointestinal
      bleeding until the real source is recognized. Clinical attacks of epigastric pain
      followed by GI-bleeding 30-40 minutes later are characteristic. Occasionally
      these attacks are followed by transient jaundice. The present case report
      describes this rare complication and reviews the current literature.

PMID- 8268108
TI  - Massive necrotizing pancreatitis in an immunosuppressed renal transplant
      recipient (successful therapy).
AB  - Severe pancreatitis may be associated with massive necrosis of the pancreas
      and/or retroperitoneal adipose tissue. Toxicity results from the dead tissue and
      secondary infection. A 45 year old patient, while fully immunosuppressed,
      developed this complication following cadaveric renal transplantation. He
      survived continued immunosuppression, 16 operative debridements of the
      retroperitoneum, and maintained a functioning renal transplant. In view of the
      previously reported high mortality rates from mild pancreatitis after
      transplantation, the current experience warrants further evaluation of the open
      method of treatment.

PMID- 8268109
TI  - Long-term survival in a patient following resection for carcinoma of the
      gallbladder and rectum.
AB  - We describe a 66-year-old man who presented initially with acute cholecystitis.
      He was treated by cholecystostomy and biopsy of the gallbladder mucosa which
      revealed carcinoma of the gallbladder. Four weeks later a cholecystectomy was
      performed followed by resection of the common bile duct, common hepatic duct and
      segments IV and V of the liver and a hepaticojejunostomy. Sixteen months later an
      abdomino-perineal resection was performed for a moderately differentiated Dukes'
      stage C carcinoma of the rectum. He is alive and without evidence of recurrence
      seven years later. Few patients survive for this length of time following
      resection of either carcinoma of the gallbladder or rectum. This case report
      demonstrates the value of aggressive surgical treatment in patients with early
      carcinoma of the gallbladder.

PMID- 8268110
TI  - Incidence of gallbladder carcinoma: conservative or radical surgery.

PMID- 8268111
TI  - Sclerotherapy versus propranolol after a variceal bleed.

PMID- 8268112
TI  - Sclerotherapy failure salvage by oesophageal transection?

PMID- 8268113
TI  - The effect of biliary decompression on bacterial translocation in jaundiced rats.
AB  - Patients with obstructive jaundice are prone to septic complications after
      biliary tract operations. Restoring bile flow to the intestine may help to
      decrease the complication rate. The present study is aimed at evaluating the
      effect of biliary decompression on bacterial translocation in jaundiced rats.
      Sixty-six male Sprague-Dawley rats were randomly allocated to six groups
      subjected to common bile duct ligation (CBDL) and transection (groups 2-6) or
      sham operation (group 1). In groups 1 and 2 the incidence of enteric bacterial
      translocation was determined 2 weeks after sham operation or CBDL. In groups 3-6,
      biliary decompression was achieved by performing a choledochoduodenostomy after 2
      weeks of biliary decompression. Bacterial translocation was then studied 1, 2, 3
      and 5 weeks following biliary decompression. The rate of bacterial translocation
      to mesenteric lymph nodes in obstructive jaundice was significantly higher as
      compared with controls and decreased with time to nil three weeks following
      biliary decompression. The incidence of bacterial translocation was closely
      correlated (r = 0.844; p = 0.034) with serum alkaline phosphatase activity and
      seemed to fit with the morphological changes noted in the small intestine. The
      decrease in bacterial translocation, however, lags behind the recovery of liver
      function as measured by routine liver function tests and antipyrine clearance.
      Obstructive jaundice thus promotes bacterial translocation in the rat. Biliary
      decompression gradually decreases the rate of bacterial translocation.

PMID- 8268114
TI  - The sympathetic nervous system in post-herpetic neuralgia.

PMID- 8268115
TI  - Relationship between time of treatment of acute herpes zoster with sympathetic
      blockade and prevention of post-herpetic neuralgia: clinical support for a new
      theory of the mechanism by which sympathetic blockade provides therapeutic
      benefit.
AB  - BACKGROUND AND OBJECTIVES: Since Rosenak's original report more than 50 years ago
      as to the efficacy of sympathetic blocks in terminating acute herpes zoster, many
      investigators have reported that a more important benefit of this form of therapy
      is the prevention of post-herpetic neuralgia. However, most of these reports have
      indicated that sympathetic blocks are effective in preventing post-herpetic
      neuralgia only if applied soon after the onset of the acute phase of the disease;
      in fact, if applied too late, this form of therapy failed to prevent the
      development of post-herpetic neuralgia. The present study was carried out to
      determine more precisely the relationship between the time of treatment of acute
      herpes zoster and the prevention of post-herpetic neuralgia and to attempt to
      correlate this time with the authors' previously published theory on the
      mechanism by which sympathetic blocks provide the therapeutic benefit. METHODS:
      The present study was a retrospective review of 122 patients treated at variable
      intervals after the onset of acute herpes zoster. Data tabulated included the
      duration of symptoms at the time of treatment, the number of sympathetic blocks
      required to provide relief, and the efficacy of the sympathetic blockade in
      terminating the acute phase of herpes zoster and then preventing the development
      of post-herpetic neuralgia. RESULT: According to the data obtained in this
      retrospective study, sympathetic blocks terminated the pain of acute herpes
      zoster and prevented or relieved post-herpetic neuralgia in more than 80% of
      patients treated within 2 months of the onset of the acute phase of the disease,
      after which time the success rate decreased drastically. CONCLUSION: Sympathetic
      blockade applied within the first 2 months after the onset of acute herpes zoster
      terminated the acute phase of the disease, probably by restoring intraneural
      blood flow, thus preventing the death of the large fibers and avoiding the
      development of post-herpetic neuralgia. If sympathetic blocks were to be carried
      out after 2 months, the damage to the large fibers would be irreversible, and
      this therapeutic modality would not be able to prevent the development of post
      herpetic neuralgia.

PMID- 8268116
TI  - Chronic exposure to lidocaine does not alter flux through sodium channels in
      cultured neuronal cells.
AB  - BACKGROUND AND OBJECTIVES: Although tachyphylaxis to local anesthetics has been
      reported in the clinical literature for more than two decades, the molecular
      mechanism(s) remain unknown. The authors described an attempt to create an in
      vitro model for tachyphylaxis to local anesthetics using cultured neuronal cells.
      METHODS: Murine neuroblastoma cells (N1E115) and rat pheochromocytoma cells (PC
      12) were grown in the presence or absence of lidocaine or tetrodotoxin for
      between 1 and 14 days. Thereafter, the authors tested flux through sodium
      channels by measuring total and tetrodotoxin-sensitive flux of 14C-labeled
      guanidinium (a ligand for the sodium channel) into the cells using the technique
      of Jacques et al. RESULTS: Chronic lidocaine or tetrodotoxin treatment caused no
      change relative to control cells in total or tetrodotoxin-sensitive guanidinium
      flux, or in the subsequent ability of lidocaine in the flux assay mixture to
      inhibit guanidinium flux. CONCLUSIONS: The authors concluded that chronic
      lidocaine or tetrodotoxin application did not produce changes in stimulated
      sodium channel activity or subsequent lidocaine susceptibility in this model. To
      the extent that this model simulated the clinical situation, mechanisms other
      than up-regulation of sodium channel number or maximal stimulated flux per
      channel may have been responsible for producing tachyphylaxis.

PMID- 8268117
TI  - A comparison between lidocaine alone and lidocaine with meperidine for continuous
      spinal anesthesia.
AB  - BACKGROUND AND OBJECTIVES: Experimental investigations have demonstrated a
      synergistic interaction between opioids and local anesthetics. This study aims to
      assess the effective benefit-risk ratio of continuous spinal anesthesia (CSA)
      induced with either 1.6% lidocaine alone or in combination with 1% meperidine.
      METHODS: Thirty-four elderly patients (80.7 +/- 7.3 years) operated on for
      fracture of the neck of the femur were randomly allocated to two groups. In the
      first group (n = 15), CSA was induced with lidocaine 1.6% plain, whereas in the
      second group (n = 19) 1% meperidine was added. Reinjections were performed in
      both groups using lidocaine 1.6% alone. RESULTS: In the lidocaine group, 43 +/-
      13 mg was used for induction whereas in the other group the addition of 18 +/- 5
      mg of meperidine significantly reduced the dose of lidocaine required to 28 +/- 8
      mg (p < 0.001). Delay between two reinjections was increased to 51 +/- 7 minutes
      in the lidocaine plus meperidine group, compared to 35 +/- 6 minutes in the
      lidocaine group (p < 0.001). Ephedrine was required for 9 out of the 19 patients
      in the lidocaine plus meperidine group, whereas it was required for only two
      patients in the other group (p = 0.05). Mean plasma concentrations of meperidine
      1 hour and 3 hours after induction was 45.5 +/- 12 ng/ml and 59 +/- 22 ng/ml,
      respectively, and drowsiness was observed in 95% of the patients in the second
      group. Delay before requirement for pain medication was 2.2 +/- 2 hours in the
      lidocaine group and 14.1 +/- 8 hours in the lidocaine plus meperidine group (p <
      0.001). CONCLUSIONS: The association of 1% meperidine with 1.6% lidocaine during
      the induction of CSA decreases the initial induction dose, prolongs analgesia,
      produces initial drowsiness, and provides long-lasting pain relief. However, such
      benefits are offset by some impairment of hemodynamic stability that is likely to
      make this combination of drugs unacceptable as an enhanced analgesic technique.

PMID- 8268118
TI  - Fentanyl for epidural intravascular test dose in obstetrics.
AB  - BACKGROUND AND OBJECTIVES: Although dizziness and drowsiness may be produced with
      either intravenous or epidural fentanyl, their occurrence after an intravenous
      injection is more rapid and relatively more pronounced. The purpose of this study
      was to determine whether or not the difference between routes of administration
      would be a reliable method of detecting an accidental intravascular injection.
      METHODS: In part 1, using a double-blinded protocol, we prospectively assessed in
      laboring women the incidence of dizziness, drowsiness, or both associated with
      intravenous fentanyl (100 micrograms). In random order, subjects received two
      peripheral intravenous injections: 2 ml of fentanyl and 2 ml of saline, separated
      by a 3-minute observation period. RESULTS: In group 1 (18/18) and group 2
      (22/22), all subjects reported a response to intravenous fentanyl within the one
      minute assessment. In part 2, we evaluated in laboring patients the frequency of
      dizziness, drowsiness, or both to epidural fentanyl (100 micrograms). The study
      design was identical to part 1; however, the subjects received 2 ml of fentanyl
      and 2 ml of saline via a functional epidural catheter. In group 3 (1/18) and
      group 4 (1/22), one subject reported a response to epidural fentanyl within the 3
      minute observation period. CONCLUSIONS: Overall, the responses to intravenous
      fentanyl (40/40) occurred in a remarkably more consistent fashion when compared
      to epidural fentanyl (2/40). Thus, the results suggest that in laboring patients,
      intravenous fentanyl produces predictable and easily detectable changes that may
      be useful in identifying an epidural catheter unintentionally placed
      intravascularly.

PMID- 8268119
TI  - No antiinflammatory effect of short-term topical and subcutaneous administration
      of local anesthetics on postburn inflammation.
AB  - BACKGROUND AND OBJECTIVES: To investigate the effect of topical and subcutaneous
      administration of local anesthetics on the inflammatory response to thermal
      injury in human volunteers. METHODS: Sixteen healthy volunteers received
      identical burn injuries (49 degrees C for 6 minutes) on the right and left calves
      with a 15 x 25 mm rectangular thermode. Eight subjects had topical 5% EMLA
      applied before and after burn injury, and another eight subjects were
      administered subcutaneous 0.5% bupivacaine infiltration before burn injury on the
      right or left leg. No treatment was applied to the contralateral leg in either
      group because this served as the control. The dermal response after burn injury
      in test areas with EMLA or bupivacaine and without treatment was compared 24
      hours, 72 hours, 168 hours, and 14 days after burn injury. RESULTS: No
      significant difference was found in the area of flare, development of blister and
      ulcerations, or the intensity of inflammation after burn injury between the
      control legs and EMLA- or bupivacaine-treated legs, respectively. CONCLUSION: No
      antiinflammatory effect of short-term preinjury and postinjury topical 5% EMLA or
      subcutaneous 0.5% bupivacaine could be demonstrated after thermal injury in human
      volunteers.

PMID- 8268120
TI  - Local myotoxicity of bupivacaine in rabbits after continuous supraclavicular
      brachial plexus block.
AB  - BACKGROUND AND OBJECTIVES: Local anesthetics including bupivacaine have been
      known to be myotoxic. Continuous brachial plexus blocks with bupivacaine provide
      good postoperative pain relief, but their effects on the surrounding muscles have
      not been studied. METHODS: Eight rabbits were given continuous bilateral brachial
      plexus blocks with 0.25% bupivacaine (BUPI) and another eight (SALINE) equivalent
      volumes of saline infused into the plexus region under pentobarbital-ketamine
      sedation. At the end of the 24-hour blocks, muscle biopsies were taken from one
      side of the neck in both groups. A week later, the biopsy procedure was repeated
      on the other side. Plasma concentrations of bupivacaine were measured before and
      at the end of the 24-hour blocks. RESULTS: Inflammatory cell infiltration and
      muscle fiber necrosis were significantly more common in the BUPI than in the
      SALINE group (p < 0.001). At the end of the continuous block, predominantly
      neutrophils were found, but in the BUPI group large amounts of eosinophilic
      granulocytes also were found. A week later lymphocytes, plasma cells,
      macrophages, and fibroblasts were seen as a sign of beginning scar formation.
      Plasma concentrations of bupivacaine at 24 hours were at a nontoxic level (0.28
      0.71 microgram/ml). CONCLUSIONS: Brachial plexus blocks with bupivacaine caused
      reversible myotoxicity and inflammation in the rabbit. A week after the
      continuous blocks, muscle fiber regeneration had already started.

PMID- 8268121
TI  - Epidural catheter direction and local anesthetic dose.
AB  - BACKGROUND AND OBJECTIVES: The volume of epidural local anesthetic required to
      achieve a particular dermatomal sensory level varies significantly between
      patients. Studies have demonstrated random cephalad or caudad migration and
      direction of the epidural catheter. However, no studies have investigated the
      relationship between catheter direction and total volume of local anesthetic.
      METHODS: The study was approved by the Institutional Review Board for the
      Protection of Human Subjects. After obtaining informed consent, 28 patients (13
      men, 15 women) scheduled for elective total knee or hip replacements were
      enrolled. The epidural catheter was inserted to a depth of 3 cm at L2-3 using a
      standard 18-gauge Tuohy needle with bevel directed either cephalad or caudad.
      After test dose, incremental volumes of 0.75% bupivacaine were injected to
      achieve a sensory anesthetic level of T6, and the total volume of drug was
      recorded. Immediately after surgery, 1 ml of omnipaque dye was injected through
      the catheter for x-ray determination of catheter-tip position. Statistical
      analysis used the Student's t-test and the Wilcoxon's rank sum test. RESULTS:
      Ages varied from 47 to 79 years (mean age, 66.5 +/- 8.51 years). Weight ranged
      from 51 to 125 kg (mean weight, 81.7 +/- 14.1 kg). Height ranged from 143 to 188
      cm (mean height, 164.2 +/- 10.6 cm). All patients had good surgical anesthesia.
      Statistically significant differences (p < .001) were seen between average
      volumes necessary to achieve a T6 sensory level for catheters in the caudad
      direction (19.2 ml, n = 9) and in the cephalad direction (13.7 ml, n = 19). No
      statistical correlations could be demonstrated between total dose of local
      anesthetic and age, sex, weight, or height. CONCLUSIONS: The authors conclude
      that epidural catheter direction influences the total dose of local anesthetic
      required to achieve a specific sensory level in epidural anesthesia.

PMID- 8268122
TI  - Treatment of persistent cough after stellate ganglion block.

PMID- 8268123
TI  - Epidural blood patch improves postdural puncture headache in a patient with
      benign intracranial hypertension.
AB  - Benign intracranial hypertension (BIH) is a disorder of elevated resting
      intracranial pressure without associated intracranial abnormality. When medical
      therapy fails to halt visual impairments or recalcitrant headaches progress,
      lumbar dural puncture and cerebral spinal fluid (CSF) drainage procedures are
      instituted. The authors report on a patient with BIH in whom a severe postdural
      puncture headache (low CSF pressure syndrome) paradoxically developed after
      therapeutic CSF drainage. This postdural puncture headache was successfully
      treated with an epidural blood patch without complicating the patient's
      underlying BIH condition.

PMID- 8268124
TI  - Reevaluating the sciatic nerve block: another landmark for consideration.

PMID- 8268125
TI  - The dribble speed for spinal anesthesia.

PMID- 8268126
TI  - Reimbursement for chronic pain management services: the cloud's silver lining.

PMID- 8268127
TI  - IL-2-dependent induction of G1 cyclins in primary T cells is not blocked by
      rapamycin or cyclosporin A.
AB  - Autocrine stimulation of the IL-2 receptor (IL-2R) is required for commitment of
      a T cell to enter the cell cycle and may involve transmission of the IL-2R signal
      to cell cycle control proteins. Candidates for such proteins are the D-type
      cyclins which are expressed in G1. Short-term cultures of primary human T cells
      were used to show that expression of cyclins D2 and D3 is regulated by IL-2 in a
      concentration- and time-dependent manner. Cyclin D2 RNA was induced rapidly to
      peak levels well before initiation of DNA synthesis and gradually declined during
      the remainder of G1. Cyclin D3 RNA and protein showed a slower induction during
      G1 to maximal levels as cells initiated DNA synthesis that remained high
      throughout S phase. Induction of cyclins D2 and D3 was independent of the
      cyclosporin A-sensitive calcineurin pathway and of rapamycin-sensitive pathways,
      despite the ability of rapamycin to severely inhibit entry into S phase. These
      observations suggest that cyclins D2 and D3 may monitor the IL-2R signal but that
      their induction does not guarantee entry into S phase. Rapamycin was found to
      target a pathway late in G1 that is distal to induction of D-type cyclin gene
      expression but proximal to DNA replication, perhaps involving the function of the
      D-type cyclin proteins or their associated kinases.

PMID- 8268128
TI  - Pseudo-high-affinity IL-2 receptor and growth signal transduction in lymphocytes.
AB  - We examined whether the pseudo-high-affinity IL-2 receptor (IL-2R) could
      transduce a growth signal in lymphocytes. Since lymphocytes devoid of the I chain
      were not available, we employed functional depletion of the I chain from a mouse
      T cell line CTLL-2 transfected with cDNA for the human H chain and its defective
      mutants which can bind IL-2 but cannot transduce a growth signal. The numbers of
      human H, mouse I, and mouse H chains expressed in these transfectants were
      similar to each other. When the human H chain (and mutants) -expressing CTLL-2
      transfectants were incubated with 300 pM human IL-2, the majority of human H and
      mouse I chains together with the L chain formed the high-affinity receptor
      complex whereas the majority of mouse H chains remained free. When the human H
      chain mutant-expressing CTLL-2 transfectants were incubated with 300 pM human IL
      2, the I chain was expected to be functionally depleted by the formation of the
      inactive high-affinity complex with the inactive human H chain mutants. However,
      the human H chain mutant-expressing CTLL-2 transfectants proliferated with a half
      maximal response to human IL-2 at 300-500 pM which agrees with the pseudo-high
      affinity Kd value displayed by the mouse L and H chains. The human H chain
      expressing transfectants proliferated in response the human IL-2 in a similar
      kinetics with CTLL-2. CTLL-2 and the human H chain/mutants-transfectants all
      responded to mouse IL-2 in the same kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268129
TI  - Is CD8 dependence a true reflection of TCR affinity for antigen?
AB  - Cytotoxic T lymphocytes (CTL) are generally specific for class I MHC proteins
      plus antigen and express CD8 co-receptor molecules. The effector function of some
      CTL can be blocked by antibodies to CD8 (CD8 dependent CTL), whereas that of
      others is resistant to blocking (CD8 independent CTL). This difference in
      sensitivity to antibody-mediated inhibition is assumed to reflect variations in
      affinity of particular TCR for antigen. However, we have found that a major
      difference between CD8 independent and CD8 dependent T cells lies in their
      sensitivity to stimulation, the former responding to lower concentrations of anti
      CD3 antibody than the latter. Thus the contribution to cell signalling provided
      by the co-association of p56lck and CD8 is particularly relevant for CD8
      dependent cells. These data challenge the notion that the affinity of an
      individual TCR for antigen is related to the sensitivity of a cell to inhibition
      by anti-CD8 antibodies. Furthermore we show that antibodies to co-receptor
      molecules have multiple distinct effects on T cell activation, only some of which
      may be related to T cell affinity.

PMID- 8268130
TI  - Natural peptide ligand motifs of two HLA molecules associated with myasthenia
      gravis.
AB  - The peptide motifs of two HLA molecules, B8 and DR3(17), which are associated
      with autoimmune diseases including myasthenia gravis, were determined from
      natural peptide pools using Edman degradation. The majority of HLA-B8 ligands are
      nonamers preferentially terminated by leucine. As a characteristic feature of the
      HLA-B8 motif, there is a high degree of conservation of positively charged amino
      acids at position 3 and 5, exclusively lysine at position 3, and lysine or
      arginine at position 5. Additional evidence for this allele-specific motif is the
      presence of these features in several viral peptides recognized by HLA-B8
      restricted T cells. The DR3(17) motif is characterized by four conserved anchor
      like positions ordered in an almost symmetrical arrangement, as has been found
      for DR1 and DR5 motifs. A first hydrophobic/aromatic anchor three to four
      residues apart from the N-terminus (at relative position 1) appears to be a
      common feature of DR ligands. The second anchor is an aspartate at relative
      position 4, which is likely to be the DR3(17)-specific contact site in the
      groove. Two additional conserved positions closer to the C-terminus are occupied
      by charged amino acids at relative position 6 and by hydrophobic/aromatic
      residues at positions 8, 9, or 10. Eight individual naturally processed DR17
      ligands were sequenced and were found to be derived from exogenous proteins and
      cytoplasmic membrane receptors. These natural peptides conform well to the
      determined motif. A single exchange of the anchor-like positions in a model
      peptide abrogated binding to DR17+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268131
TI  - Maturation of human myelomonocytic leukemia cells following ligation of the low
      affinity receptor for IgE (Fc epsilon RII/CD23).
AB  - The regulation of the low affinity receptor for IgE (Fc epsilon RII/CD23)
      expression and its role were investigated in U937 cell line and in leukemic cells
      from a patient (Amb) with acute myeloblastic leukemia. Both cell populations were
      CD23- but could acquire CD23 expression following treatment with IL-4. CD23+
      cells, however, remained blastic and did not show any significant phenotypical
      and functional modifications. Following ligation of the CD23 on U937 and Amb
      cells by anti-CD23 mAb, these leukemic cells differentiated into mature
      monocyte/macrophage-like cells. CD23 ligation promoted the expression of the
      monocyte marker, CD14, increased the expression of the common beta chain of the
      LFA-1 family (CD18), and down-regulated the expression of the promonocytic marker
      CD33. Morphological and phenotypical changes were associated with functional
      modifications as CD23 ligation allowed the acquisition of the oxidative
      metabolism in leukemic cells as revealed by luminol-dependent chemiluminescence.
      As in mature monocytes, CD23 ligation induced an accumulation of intracellular
      cAMP in leukemic cells. These data indicate that ligation of CD23 may induce the
      maturation of myelomonocytic cells into monocytic-like cells.

PMID- 8268132
TI  - Is the activated T helper stimulus able to induce Ig isotype switching in
      cultured human B cells?
AB  - It is confirmed that large amounts of IgM, IgG, and IgA are produced when human B
      cells are cultured with T cells activated by immobilized CD3 antibody (CD3
      system). IL-2 was essential; lower levels of Ig production with different isotype
      ratios were obtained if IL-4 or IL-6 replaced IL-2. Depletion of sIgG+ or sIgA+
      cells from the B population to be cultured markedly reduced production of IgG or
      IgA. Cultures of B cells selected with the pan-B markers CD19, CD72, or CD21
      contained similar levels of Ig of all three isotypes, whereas B cells selected
      for sIgM or sIgD expression produced IgM but very little IgG or IgA indicating
      that little isotype switching was occurring. Production of IgG or IgA from cells
      expressing these isotypes was more efficient than production of IgM from IgM+IgD+
      cells. These results are considered in the light of the demonstration by others
      of the production of multiple isotypes from single sIgM+-selected B cells. Cloned
      human T cells from a single donor induced production of all three isotypes, but
      the proportions varied indicating that the potent T-B cell interactions inducing
      B cell activation may override and conceal the operation of isotype specific cell
      interactions. Some T clones used at an optimal dose were as effective untreated
      as X-irradiated, whereas with other clones maximum Ig production was not achieved
      without irradiation.

PMID- 8268133
TI  - HLA-DR and H-2E transgenes differentially mediate TCR-specific positive
      selection.
AB  - The use of HLA transgenic mice in models of immunity and disease assumes that
      human MHC molecules are able to contribute toward the positive selection of the
      mouse TCR repertoire. As an initial step towards analysis of this we have
      compared the relative ability of DR alpha/E beta or E alpha/E beta complexes to
      induce T cell receptor (TCR) positive selection in H-2Ea and HLA-DRA transgenic
      mice lacking endogenous E alpha. The results show that, like E alpha/E beta, the
      hybrid DR alpha/E beta complexes are capable of mediating positive selection of V
      beta 2+, V beta 6+, and V beta 10+ cells. However, differences were found between
      the effects of the two transgenes. Thus, while V beta 6+ cells were efficiently
      selected in both H-2Ea and DRA transgenic mice, positive selection of V beta 10+
      cells was less apparent in the DRA transgenic mice. Variation between Ea and DRA
      transgenic mice is consistent with the notion that this process is dependent on
      differential binding of endogenous peptides to the E alpha/E beta and DR alpha/E
      beta complexes. Furthermore, contrary to expectations, in neither set of mice was
      positive selection limited solely to the CD4+ subset. Thus, examples were found
      in which V beta-specific positive selection was confined to either the CD4+ or
      CD8+ subsets, and others in which both subpopulations were concomitantly
      increased. In the case of V beta 2 positive selection, H-2Ea transgenic mice
      showed expansion of these cells in both the CD4+ and CD8+ subpopulations while in
      DRA transgenic mice this occurred predominantly in the CD8+ subpopulation.

PMID- 8268134
TI  - T cell deletion follows chronic antigen specific T cell activation in vivo.
AB  - Exposure of mice transgenic for a TCR (F5) to cognate peptide antigen results in
      thymic depletion of CD4+CD8+ cells and expansion and activation of peripheral
      CD8+ TCR(tg)+ T cells. In the thymus apoptotic DNA ladder is evident as early as
      3 h after peptide injection. Long exposure of intact or thymectomized F5 TCR
      transgenic mice to peptide antigen leads to depletion of most of the peripheral
      CD8+ T cells bearing the F5 receptor, with the remaining cells having lower
      levels of transgenic TCR compared with non-treated animals. In the thymus of
      intact F5 TCR transgenic mice such continuous exposure to antigen results in the
      reappearance of CD4+CD8+ with lower levels of the transgenic receptor.

PMID- 8268135
TI  - The role of the 16/6 idiotype network in the induction and manifestations of
      systemic lupus erythematosus.
AB  - Experimental systemic lupus erythematosus (SLE) has been induced in mice by
      immunization with either a human anti-DNA mAb bearing a common idiotype (Id)
      designated 16/6 Id (antibody 1, Ab1) or with a murine anti-16/6 Id mAb (Ab2). In
      the present study a murine mAb (5G12-4, Ab3) that bears the 16/6 Id and binds to
      DNA was produced and was found to bind rabbit anti-16/6 Id sera and murine anti
      16/6 Id mAb similarly to the human mAb 16/6 Id (Ab1). Moreover, mAb 5G12-4 was
      shown to share T cell epitopes with the human 16/6 Id mAb, since lymph node cells
      of mice immunized with the mAb 5G12-4 proliferated significantly to the human
      16/6 mAb and vice versa. Following immunization of mice with the murine mAb
      bearing the 16/6 Id, antibodies to dsDNA, ssDNA, 16/6 Id, anti-16/6 Id, and to
      HeLa nuclear extract proteins were detected, similarly to those observed
      previously upon immunization with Ab1 or Ab2. Six months following the
      immunization, the mice exhibited leukopenia, increased erythrocyte sedimentation
      rates, and proteinuria. Examination of the kidneys of the mice disclosed immune
      complex deposits, thickening of the Bowman's capsule and glomerular necrosis.
      These results show the importance of the 16/6 Id network in the induction and
      progression of SLE in mice.

PMID- 8268136
TI  - Priming of cytotoxic T lymphocytes at various stages of ontogeny with
      transfectoma cells expressing a chimeric Ig heavy chain gene bearing an influenza
      virus nucleoprotein peptide.
AB  - The amino acid residues 147-161 of the nucleoprotein (NP) of influenza virus
      represent a T cell epitope recognized by cytotoxic T cells (CTLs) in association
      with Kd class I molecules. When SP2/0 myeloma B cells are transfected with a
      chimeric heavy chain gene bearing this particular NP(147-161) peptide, they are
      lysed by CTLs specific for the NP(147-161) peptide. Cells that are transfected
      with this heavy chain chimera and the parental light chain secreted a soluble Ig
      NP chimera and were also lysed by the CTLs. Herein, we present evidence that
      transfectoma cells are able to induce in vitro proliferation of NP specific CTL,
      whereas immobilized Ig-NP chimeras do not. Furthermore, the transfectoma cells
      expressing the chimeric heavy chain prime NP specific CTLs in adult as well as in
      newborn mice, while SP2/0 cells coated with NP(147-161) synthetic peptide do not.
      These data indicate that the NP peptide needs to be cleaved from the Ig context
      in order to be presented to T cells and that only endogenously generated NP
      peptide is immunogenic.

PMID- 8268137
TI  - Signal transduction in human B cells initiated via Ig beta ligation.
AB  - Ig alpha and Ig beta heterodimers are non-covalently associated with Ig to
      compose the antigen receptor complexes on B cells. The demonstration that
      different sets of tyrosine kinases bind to the cytoplasmic tails of Ig alpha and
      Ig beta suggests that Ig alpha and Ig beta may activate distinct second messenger
      pathways. In this study, we examined the effects of mAbs against an exposed
      epitope of human Ig beta on pre-B and B cell triggering. Cross-linkage of Ig beta
      on B cells leads to activation of tyrosine kinases, hydrolysis of
      phosphatidylinositides, and elevation of intracellular Ca2+, effects
      qualitatively identical to those of anti-mu mAbs. Our observations thus indicate
      that cross-linking of Ig beta does not segregate signal transduction pathways
      connected with the cytoplasmic tails of Ig alpha and Ig beta. Ig alpha ligation
      has been reported to be more effective in triggering pre-B than B cells, whereas
      our results indicated that Ig beta ligation is more efficient in triggering B
      than pre-B cells. In addition to their activation properties, the anti-Ig beta
      mAbs effectively modulated B cell receptor complexes and blocked terminal
      differentiation of all plasma cell isotypes. The findings support the idea that
      anti-Ig beta could serve as a universal B cell immunosuppressant.

PMID- 8268138
TI  - A rheumatoid factor transgenic mouse model of autoantibody regulation.
AB  - To address whether B cells expressing a disease-associated autospecificity are
      regulated in normal mice, we have established a rheumatoid factor (RF) transgenic
      model of autoimmunity, using V genes derived from an IgA anti-IgG2a RF isolated
      from an autoimmune MRL/lpr mouse. As we wished to study induction of tolerance
      during B cell development, we cloned the VH gene into an IgM expression vector.
      The RF we chose binds only IgG2a of the 'a' allotype (IgG2a) but not IgG2ab
      allowing us to produce transgenic animals on IgHa and IgHb backgrounds, which
      either express or lack the self-antigen. Two transgenic lines were studied. Using
      mice which lack the self-antigen, we show by fluorescence activated cell sorting
      and hybridoma analysis that the H and L transgenes are expressed to the exclusion
      of endogenous genes in most splenic B cells. In spite of good allelic exclusion,
      transgenic mice which are genetically capable of expressing IgG2aa have reduced
      but significant (approximately 50 micrograms/ml) serum levels. Nonetheless, the
      frequency and numbers of transgene-expressing B cells in peripheral lymphoid
      organs of such mice which have the self-antigen are similar to those which lack
      it (IgHb mice). Thus, B cells expressing an anti-self IgG2a surface receptor can
      develop in this system. Whether such B cells are anergic or otherwise regulated
      in autoantigen-expressing mice is discussed.

PMID- 8268139
TI  - Altered response of CD4+ T cell subsets to Plasmodium chabaudi chabaudi in B cell
      deficient mice.
AB  - Mice depleted of B cells from birth by treatment with anti-mu antibodies can
      control but not clear an infection with the malaria parasite Plasmodium chabaudi
      chabaudi (AS). Splenic CD4+ T cells from these mice were unable to mount a
      significant Th2 response to the parasite in vitro as shown by much lower
      precursor frequencies of Th cells for antibody production and of IL-4-producing
      cells compared with the response of control-treated mice. CD4+ T cells of the
      anti-mu-treated mice which respond to antigens of P. chabaudi chabaudi maintained
      a Th1 phenotype throughout primary infection, in contrast to control mice in
      which a sequential appearance of Th1 and Th2 responses was observed. These data
      show that Th1 responses in anti-mu-treated mice are sufficient to control
      parasitemia but not to eliminate an infection. The data further suggest that
      depletion of B cells by treatment with anti-mu antibodies reduces the generation
      of the Th2 subset during a primary response to P. chabaudi chabaudi.

PMID- 8268140
TI  - Gangliosides can activate human alternative complement pathway.
AB  - The alternative complement pathway (ACP) in vertebrates is known to be important
      in inflammatory reactions, and to be activated by foreign substances such as
      bacterial lipopolysaccharide (LPS) and zymosan, although to date no intrinsic
      activators have been identified except complement receptor type 2. From the point
      of the structural similarity of LPS to ganglioside, we have investigated
      gangliosides which are abundantly present in animal cells for their activity on
      the human ACP. All of seven gangliosides tested were found to activate this
      pathway in a manner depending on the number of sialic acids and neutral sugars
      contained in the molecules. A dose-response study suggested a correlation of the
      threshold in ganglioside concentration with its critical micelle concentration.
      Gangliosides may thus serve as an intrinsic activator for ACP in animals, thereby
      leading to inflammation. The possibility of the participation of sialidase in
      complement activation is also discussed.

PMID- 8268141
TI  - Early outcome of PTCA in totally occluded coronary arteries.
AB  - BACKGROUND: Since percutaneous transluminal coronary angioplasty (PTCA) was first
      introduced in 1977 by Gruentzig as a treatment for proximal short-segmental, non
      calcified, concentric isolated coronary stenosis, it has been used with
      increasing frequency in patients of symptomatic coronary artery disease with
      broader indications, including patients with multi-vessel disease, unstable
      angina, acute myocardial infarction and totally occluded coronary arteries. Among
      these, total coronary occlusion constitutes a subdivision with specific features
      that require separate evaluation. The purpose of this study was to determine the
      initial results of PTCA for total coronary occlusion. METHODS: Thirty-five
      patients with manifested ischemic heart disease with totally occluded coronary
      arteries, documented by coronary angiography, underwent recanalization procedure
      by PTCA between Jan. 1990 and Oct. 1991. RESULTS: Thirty-five patients were
      comprised of 20 acute myocardial infarction (MI), 7 old MI and 8 unstable angina.
      Eighteen (50.1%) patients had one major atherosclerosis risk factor and 10
      (29.4%) had two or more. PTCA for total coronary artery occlusion was attempted
      in the left anterior descending artery (LAD) in 16 patients, right coronary
      artery (RCA) in 11, left circumflex artery (LCx) in 2 and protected left main in
      one. PTCA was successful in 23 patients (66%): LAD in 11/18 (61%) and RCA 11/14
      (79%), showing significantly higher success rate with RCA than LAD (p < 0.05).
      Primary success rate of PTCA in accordance with the duration of the total
      occlusion estimated on the basis of clinical and angiographic data was 71%
      (15/21) when less than two weeks, 63% (5/8) when between 2 to 12 weeks, and 50%
      (3/6) longer than 12 weeks. Mean duration of the total occlusion in successful
      PTCA was 1.4 months (range; 10 days-5 months) and, 1.7 months (range; 3 weeks-3
      years) in failed PTCA. Diameter stenosis of the lesions was significantly
      decreased from 100% to 19.7% after successful PTCA. There was no death but 2
      patients were complicated with coronary artery embolization occluding major
      distal branches. CONCLUSION: The study suggested that PTCA of total coronary
      artery occlusion can be performed safely and effectively in selected cases and
      might be more successful in the lesion with shorter duration of occlusion.

PMID- 8268142
TI  - Antral Helicobacter pylori infection, hypergastrinemia and peptic ulcers: effect
      of eradicating the organism.
AB  - BACKGROUND: A randomized prospective study on the response of fasting serum
      gastrin concentrations in peptic ulcer patients was performed in order to test
      the hypothesis that H. pylori infection in the gastric antrum increases gastrin
      release, and to examine whether the high fasting serum gastrin concentrations
      respond to treatment that eradicates H. pylori. METHODS: One hundred and twenty
      seven patients with gastric or duodenal ulcer were included in this study.
      Patients were divided into three groups on the basis of antral H. pylori status
      and therapeutic modalities. The first group, 58 patients infected by H. pylori,
      was treated with metronidazole and tripotassium dicitrato bismuthate combined
      with ranitidine and mylanta. The second group, 40 patients also infected by H.
      Pylori, was treated with ranitidine and mylanta. The third group, 29 patients,
      free of H. pylori infection, was designed to evaluate the influence of H2
      receptor antagonist on the change of gastrin. When ulcers were completely healed,
      changes of gastrin concentrations and H. pylori status were re-examined. RESULTS:
      H. pylori was eradicated in all patients who have received antibacterial therapy
      in 4 weeks, and serum gastrin concentrations were significantly decreased after
      eradication of the organism both in gastric and in duodenal ulcer diseases.
      (Gastric ulcer: 129.3 +/- 47.0 pg/ml before and 63.7 +/- 21.6 pg/ml after
      treatment. Duodenal ulcer: 108.3 +/- 35.0 pg/ml and 66.5 +/- 21.9 pg/ml,
      respectively. Total: 112.7 +/- 38.2 pg/ml vs 66.0 +/- 21.6 pg/ml) (p < 0.01). In
      contrast, H. pylori-positive patients who have not received antibacterial therapy
      were still infected at the completion of the study, and serum gastrin
      concentrations increased even though the difference was not significant. (Gastric
      ulcer: 118.4 +/- 51.2 pg/ml vs 124.0 +/- 56.5 pg/ml. Duodenal ulcer: 85.4 +/-
      35.1 pg/ml vs 104.6 +/- 43.5. Total: 99.5 +/- 45.3 vs 112.9 +/- 48.7 pg/ml.) (p >
      0.05). None of the patients who were initially H. pylori-negative has been
      reinfected during the period of the study, and their serum gastrin concentrations
      were not changed. (Gastric ulcer: 69.8 +/- 38.0 pg/ml. Total: 63.2 +/- 31.1
      pg/ml. Duodenal ulcer: 55.1 +/- 17.6 pg/ml vs 55.8 +/- 13.8 pg/ml. Total: 63.2 +/
      31.1 pg/ml vs 63.4 +/- 30.0 pg/ml). Four- to six-week therapy of H2-receptor
      antagonist and antacid had no influence on serum gastrin concentrations.
      CONCLUSIONS: On the basis of the above results, we confirmed that the chronic
      infection of H. pylori of gastric antrum in peptic ulcer patients causes
      increased release of serum gastrin, and eradication of the organism results in a
      significant fall in serum gastrin concentrations.

PMID- 8268143
TI  - Mycobacterium fortuitum peritonitis associated with continuous ambulatory
      peritoneal dialysis.
AB  - Runyon group IV atypical mycobacteria, Mycobacterium fortuitum, is an
      environmental organism and is capable of producing a variety of clinical
      infections such as cutaneous infection, abscess and pulmonary and ocular
      infection. Rarely, it has been a documented cause of peritonitis in patients
      receiving continuous ambulatory peritoneal dialysis (CAPD). We report a case of
      M. fortuitum peritonitis in a patient undergoing CAPD and emphasize the
      importance of mycobacterial cultures in patients with CAPD-associated peritonitis
      whose routine culturing yields no organisms repeatedly.

PMID- 8268144
TI  - Cimetidine improves the accuracy of creatinine clearance as an indicator for
      glomerular filtration rate.
AB  - BACKGROUND: Although endogenous creatinine clearance is often used as an
      indicator for the glomerular filtration rate (GFR), it may result in an
      overestimation due to its tubular secretion. Since cimetidine is known to inhibit
      tubular secretion of creatinine, it may improve the accuracy of the creatinine
      clearance in measuring GFR. METHODS: Creatinine clearance (Ccr) was compared with
      iothalamate clearance (C1oth) during oral administration of either placebo or
      cimetidine in 25 patients with varying degrees of renal dysfunction. RESULTS:
      Cimetidine itself had no effect on C1oth but decreased Ccr, improving its
      validity, as measured by a significant decrease of Ccr/C1oth from 1.72 during
      placebo to 1.17 during cimetidine administration. The degree of overestimation
      measured by the Ccr was more pronounced in those with more severe renal
      dysfunction. A significant inverse correlation was noted between Ccr/C1oth and
      GFR. No apparent side effect due to cimetidine was noted. CONCLUSIONS: These
      results suggest that cimetidine improves the accuracy of Ccr as an indicator for
      GFR in patients with varying degrees of renal dysfunction.

PMID- 8268145
TI  - Manning criteria in irritable bowel syndrome: its diagnostic significance.
AB  - BACKGROUND: Irritable bowel syndrome is one of the most commonly encountered
      gastrointestinal disorders, for which there are no established diagnostic
      criteria. Thus, a diagnosis of IBS is made by exclusion of any organic diseases.
      Recently, important attempts for the positive diagnosis of irritable bowel
      syndrome by questionnaire surveys of physical symptoms have been made. We
      performed a questionnaire survey to evaluate the diagnostic value of the Manning
      criteria and to observe the major symptoms in irritable bowel syndrome. METHODS:
      A symptom questionnaire which consisted of 22 items, including 6 cardinal
      symptoms of the Manning criteria, were answered by 172 outpatients who had
      gastrointestinal complaints. According to a final diagnosis based on independent
      clinical evaluation, all patients were categorized in three groups: irritable
      bowel syndrome group, nonulcer dyspepsia group and organic gastrointestinal
      disease group. The results of the questionnaire were analyzed for each group.
      RESULTS: The sensitivity and specificity of the Manning criteria for the
      diagnosis of irritable bowel syndrome were 67% and 70% if three or more items
      were regarded as positive. The mean score and overall frequency of the Manning
      criteria were significantly higher in irritable bowel syndrome group than in
      nonuclear dyspepsia (p < 0.01) or organic gastrointestinal disease group (p <
      0.05). Among subgroups of the irritable bowel syndrome group, the pain
      predominant subgroup showed a significantly higher score and overall frequency
      than the painless subgroup (p < 0.05). CONCLUSIONS: The Manning criteria would be
      useful as a simple and reliable backup tool for the diagnosis of irritable bowel
      syndrome and seem to be more useful in pain-predominant subgroup. More detailed
      history-taking should prevent unnecessary extensive investigations for the
      diagnosis of irritable bowel syndrome.

PMID- 8268146
TI  - Acute appendicitis in patients with acute leukemia.
AB  - The decision to operate for abdominal pain in patients with leukopenia can be
      exceedingly difficult. Surgical exploration may be the only effective way to
      differentiate acute appendicitis from other causes, but it involves considerable
      risk of infectious complications due to immunosuppression. Leukemic patients, who
      presented significant RLQ pain, had been indicated for operation, despite having
      advanced disease or having had received chemotherapy or steroids. Four adult
      leukemia patients, complicated by acute appendicitis, were reviewed. Two patients
      were in induction chemotherapy, one receiving salvage chemotherapy due to relapse
      and the other was in conservative treatment. Two patients were acute myelocytic
      leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had
      aleukemic leukemia. All patients underwent appendectomy and recovered without
      complication. Our experience supports the theory that the surgical management of
      appendicitis in acute leukemia is the most effective way, in spite of leukopenia.

PMID- 8268147
TI  - A case of polymyositis in a patient with primary biliary cirrhosis treated with D
      penicillamine.
AB  - Although D-penicillamine has been used for many rheumatologic diseases, toxicity
      limits its usefulness in many patients. Polymyositis/dermatomyositis can develop
      as one of the autoimmune complications of D-penicillamine treatment, but its
      exact pathogenesis remains unclear. We report a patient with primary biliary
      cirrhosis, who developed polymyositis while receiving D-penicillamine therapy. We
      described the special clinical course of the patient. Patients receiving D
      penicillamine therapy should be followed carefully for the development of
      autoimmune complications like polymyositis/dermatomyositis.

PMID- 8268148
TI  - A case of primary intestinal lymphangiectasia.
AB  - A 26-year-old male patient who had an 8 years history of recurrent peripheral
      edema with diarrhea and hypoproteinemia was evaluated. Endoscopic jejunal and
      ileal biopsy revealed markedly dilated mucosal lymph vessels with no evidence of
      inflammation. 99mTc-labeled human serum albumin (HSA) scintigraphy showed
      significant activity accumulating in the gastrointestinal tract to represent
      99mTc-HSA leakage into the bowel lumen. A diagnosis of protein losing enteropathy
      and intestinal lymphangiectasia could be made. After treatment with a high
      protein and fat restricted diet, his symptoms subsided and the serum protein
      level was normalized.

PMID- 8268149
TI  - Direct relationship between elevated free testosterone and insulin resistance in
      hyperprolactinemic women.
AB  - Women with hyperprolactinemia have been reported to have hyperandrogenemia and/or
      insulin resistance. However, little is known about the association of
      hyperandrogenemia and insulin resistance in these women. To investigate whether
      hyperandrogenemia and/or insulin resistance occur in hyperprolactinemic women,
      and to assess the relationship between them, we measured basal androgen level and
      both glucose and insulin levels after oral glucose administration in 20
      hyperprolactinemic women and 7 female control subjects. Free testosterone level
      was higher and estradiol level lower in hyperprolactinemic women than in control
      subjects (p < 0.05), whereas dehydroepiandrosterone sulfate (DHEAS) and total
      testosterone levels were similar (p > 0.05). Both fasting glucose and insulin
      levels didn't differ in the two groups (p > 0.05). However, both serum glucose
      and insulin levels, after a 75 g glucose load, were significantly increased in
      hyperprolactinemic women, (p = 0.001, p < 0.001, respectively). In simple linear
      regression analysis in hyperprolactinemic women, only free testosterone level had
      a positive correlation with the incremental area under the insulin curve (insulin
      IAU) (r = 0.47, p < 0.05). In multiple stepwise regression analysis, free
      testosterone level, mean blood pressure and DHEAS level were associated
      significantly with insulin-IAU (beta = 0.98, p < 0.0001; beta = 0.58, p = 0.002;
      beta = -0.67, p < 0.003, respectively). These results suggest that insulin
      resistance is closely related to elevated free testosterone level in
      hyperprolactinemic women.

PMID- 8268150
TI  - Structure of toxic shock syndrome toxin 1.
AB  - The three-dimensional structure of toxic shock syndrome toxin 1 (TSST-1) from
      Staphylococcus aureus has been determined and refined to an R value of 0.226 for
      data between 8- and 2.5-A resolution. Overall, the structure of TSST-1 is similar
      to that of another superantigen, staphylococcal enterotoxin B (SEB). The key
      differences between these molecules are in the amino termini and in the degree to
      which a long central helix is covered by surface loops. The region around the
      carboxyl end of this central helix is proposed to govern the superantigenic
      properties of TSST-1. An adjacent region along this helix is proposed to be
      critical in the ability of TSST-1 to induce toxic shock syndrome.

PMID- 8268151
TI  - Evidence for retention of biological activity of a non-heme iron enzyme adsorbed
      on a silver colloid: a surface-enhanced resonance Raman scattering study.
AB  - The structure and catalytic properties of the enzyme (E) chlorocatechol
      dioxygenase (CCD) adsorbed on a citrate-reduced silver colloid are analyzed by
      surface-enhanced resonance Raman spectroscopy (SERRS). This is the first SERRS
      study of a non-heme metalloenzyme. It is demonstrated that the native
      conformation of CCD is retained in the adsorbed state by comparison of resonance
      Raman scattering (RRS) from CCD in solution with SERRS from CCD adsorbed on the
      silver colloid. Both spectra show clear evidence of vibrational bands typical of
      iron-tyrosinate proteins. Furthermore, it is demonstrated that adsorbed CCD
      retains 60-85% of its enzymatic activity in the reaction of catechol substrate
      (S) with O2 to give the dioxygenated product (P) cis,cis-muconate. This is
      accomplished by enzyme assays of Ag-adsorbed CCD and comparison of the SERRS of
      Ag-adsorbed enzyme-substrate (ES) complex under anaerobic conditions with that of
      Ag-adsorbed ES in the presence of dioxygen. The SERRS difference spectrum,
      ES(aerobic)--ES(anaerobic), shows clear evidence for the appearance of the
      vibrational modes of adsorbed product. The analogous SERR difference spectroscopy
      experiment is also carried out for the enzyme-inhibitor (EI) complex of CCD with
      tetrachlorocatechol (TCC). Slow turnover of CCD-TCC is observed by SERRS on
      exposure to dioxygen which is consistent with the slow rate of turnover of TCC by
      CCD in solution.

PMID- 8268152
TI  - Cell-free synthesis, functional refolding, and spectroscopic characterization of
      bacteriorhodopsin, an integral membrane protein.
AB  - Bacteriorhodopsin (bR) is an integral membrane protein which functions as a light
      driven proton pump in Halobacterium halobium (also known as Halobacterium
      salinarium). The cell-free synthesis of bR in quantities sufficient for FTIR and
      NMR spectroscopy and the ability to selectively isotope label bR using
      aminoacylated suppressor tRNAs would provide a powerful approach for studying the
      role of specific amino acid residues. However, no integral membrane protein has
      yet been expressed in a cell-free system in quantities sufficient for such
      biophysical studies. We report the cell-free synthesis of bacterioopsin, its
      purification, its refolding in polar lipids from H. halobium, and its
      regeneration with all-trans-retinal to yield bacteriorhodopsin in a form
      functionally similar to bR in purple membrane. Importantly, the yields obtained
      from in vitro and in vivo expression are comparable. Functionality of the cell
      free expressed bR is established using static and time-resolved absorption
      spectroscopy and FTIR difference spectroscopy.

PMID- 8268153
TI  - Structure of the membrane-bound form of the pore-forming domain of colicin A: a
      partial proteolysis and mass spectrometry study.
AB  - The ion-channel-forming thermolytic fragment (thA) of colicin A binds to
      negatively charged vesicles and provides an example of the insertion of a soluble
      protein into a lipid bilayer. The soluble structure is known and consists of a 10
      helix bundle containing a hydrophobic helical hairpin. In this study, partial
      proteolysis and mass spectrometry were used to determine the accessible sites to
      proteolytic attack by trypsin and alpha-chymotrypsin in the thA fragment in its
      membrane-bound state. Electrospray mass spectrometry was quite an efficient
      method for the identification of the cleavage products, even with partially
      purified peptide mixtures and with only few controls by N-terminal sequencing.
      This work confirms that a major part of the peptide chain lies at the membrane
      surface and that even the hydrophobic hairpin is not protected by the lipid
      bilayer from proteolytic degradation. In the absence of a membrane potential, the
      hydrophobic hairpin in the colicin A membrane-bound form seems not fixed in a
      transmembrane orientation.

PMID- 8268154
TI  - Thermostabilization of firefly luciferase by a single amino acid substitution at
      position 217.
AB  - Random mutagenesis of the luciferase cDNA from "Genji" firefly, Luciola cruciata,
      was induced by hydroxylamine in an attempt to isolate thermostable mutants. Three
      mutants were isolated, and the cDNAs encoding these proteins were sequenced. All
      mutant cDNAs carried the same C to T transition mutation that conferred an amino
      acid substitution of Thr by Ile at position 217. The wild-type luciferase and the
      thermostable variant (Thr217Ile) were purified to homogeneity, and their
      enzymatic properties were determined. Thr217Ile was superior to wild-type in
      thermal and pH stability. Furthermore, the specific activity of the Thr217Ile
      mutant was increased to 130% of that of the wild-type. In order to examine the
      effect of amino acid residue substitution at position 217 on the thermostability
      of luciferase, we replaced the Thr residue at position 217 with all of the rest
      of the possible amino acid residues by site-directed mutagenesis. The
      thermostability of these substitution mutants seemed to correlate with the
      hydrophobicity of the substituted amino acid residue.

PMID- 8268155
TI  - Inactivation of pancreatic lipases by amphiphilic reagents 5-(dodecyldithio)-2
      nitrobenzoic acid and tetrahydrolipstatin. Dependence upon partitioning between
      micellar and oil phases.
AB  - We have reported previously that Cys103 (SHII) of human pancreatic lipase (HPL),
      unlike the nonessential Cys181 (SHI), was buried and inaccessible to classical
      water-soluble sulfhydryl reagents. The lipolytic activity of HPL was lost after
      the labeling of the above two SH groups with the amphiphilic sulfhydryl reagent,
      5-(dodecyldithio)-2-nitrobenzoic acid (C12-TNB), suggesting that the SHII residue
      may play an important role in the hydrolytic process [Gargouri, Y., Cudrey, C.,
      Medjoub, H., & Verger, R. (1992) Eur. J. Biochem. 204, 1063-1067]. For the
      present experiments, we selected dog pancreatic lipase (DPL), purifying it for
      the first time, and recombinant guinea pig pancreatic lipase (r-GPL), which both
      contain a buried SHII group but no accessible SHI group. The single SHII of DPL
      and r-GPL reacted only with the amphiphilic SH reagent (C12-TNB), and its
      labeling was correlated with a rapid lipase inactivation. Although it is
      spatially remote from the catalytic triad, the SHII group of pancreatic lipases,
      when chemically labeled, was found to be responsible for the loss of their
      lipolytic activity. The presence of a bulky dodecyl chain, linked by a disulfide
      bond to the SHII, may have prevented the critical beta-5 loop (residues 76-85)
      movement by steric hindrance and consequently disturbed the formation of the
      oxyanion hole. Thus, pancreatic lipase inactivation by the amphiphilic sulfhydryl
      reagent can be said to be due to the prevention of a productive induced fit.
      Tetrahydrolipstatin (THL) is an amphiphilic inactivator reacting with the
      essential serine of the lipase active site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268156
TI  - Tertiary structures of class I ubiquitin-conjugating enzymes are highly
      conserved: crystal structure of yeast Ubc4.
AB  - The three-dimensional structure of a yeast ubiquitin-conjugating enzyme, encoded
      by the Saccharomyces cerevisiae UBC4 gene, has been determined at 2.7 A. The
      structure was solved using molecular replacement techniques and refined by
      simulated annealing to an R-factor of 0.198. Bond lengths and angles in the
      molecule have root mean square deviations from ideal values of 0.018 A and 4.0
      degrees, respectively. Ubc4 is an alpha/beta protein with four alpha-helices and
      a four-stranded antiparallel beta-sheet. The ubiquitin-accepting cysteine is
      located in a cleft between two loops. Comparison with the recently determined
      structure of a different plant enzyme suggests that class I ubiquitin-conjugating
      enzymes are highly conserved in their three-dimensional folding. Except for two
      extra residues at the N- and the C-terminus of the plant enzyme, the C alpha
      atoms of the two enzymes can be superimposed with a root mean square deviation of
      only 1.52 A. Greater variations are found between the surfaces of the two
      molecules, as most of the identical residues between the two enzymes are either
      buried or clustered on the surface that lies adjacent to the ubiquitin-accepting
      cysteine. We suggest that this conserved surface functions in protein-protein
      binding during ubiquitin thiol ester formation.

PMID- 8268157
TI  - Characterization of the three-dimensional solution structure of human profilin:
      1H, 13C, and 15N NMR assignments and global folding pattern.
AB  - Human profilin is a 15-kDa protein that plays a major role in the signaling
      pathway leading to cytoskeletal rearrangement. Essentially complete assignment of
      the 1H, 13C, and 15N resonances of human profilin have been made by analysis of
      multidimensional, double- and triple-resonance nuclear magnetic resonance (NMR)
      experiments. The deviation of the 13C alpha and 13C beta chemical shifts from
      their respective random coil values were analyzed and correlate well with the
      secondary structure determined from the NMR data. Twenty structures of human
      profilin were refined in the program X-PLOR using a total of 1186 experimentally
      derived conformational restraints. The structures converged to a root mean
      squared distance deviation of 1.5 A for the backbone atoms. The resultant
      conformational ensemble indicates that human profilin is an alpha/beta protein
      comprised of a seven-stranded, antiparallel beta-sheet and three helices. The
      secondary structure elements for human profilin are quite similar to those found
      in Acanthamoeba profilin I [Archer, S. J., Vinson, V. K., Pollard, T. D., &
      Torchia, D. A. (1993), Biochemistry 32, 6680-6687], suggesting that the three
      dimensional structure of Acanthamoeba profilin I should be analogous to that
      determined here for human profilin. The structure determination of human profilin
      has facilitated the sequence alignment of lower eukaryotic and human profilins
      and provides a framework upon which the various functionalities of profilin can
      be explored. At least one element of the actin-binding region of human profilin
      is an alpha-helix. Two mechanisms by which phosphatidylinositol 4,5-bisphosphate
      can interfere with actin-binding by human profilin are proposed.

PMID- 8268158
TI  - Crystal structure of d(CGCGAATTCGCG) complexed with propamidine, a short-chain
      homologue of the drug pentamidine.
AB  - The crystal structure of the complex between propamidine and the self
      complementary DNA dodecamer d(CGCGAATTCGCG) duplex has been determined to a
      resolution of 2.1 A and a R-factor of 17.4%. The propamidine binds to the DNA
      within the minor groove, with specific hydrogen-bonding interactions from the
      amidinium groups to the bases and sugar groups of the DNA, via a 4-base-pair
      binding site. A network of water molecules lies over the mouth of the minor
      groove. The structure provides a rationale for the superior DNA-binding
      properties of propamidine as compared to pentamidine [cf. Edwards, K. J.,
      Jenkins, T. C. & Neidle, S. (1992) Biochemistry 31, 7104-7109]. This is seen to
      result from (i) decreased minor groove width at the binding site and (ii) reduced
      mobility of the bound propamidine molecule.

PMID- 8268159
TI  - XAFS studies of carboxypeptidase A: detection of a structural alteration in the
      zinc coordination sphere coupled to the catalytically important alkaline pKa.
AB  - X-ray absorption fine structure (XAFS) spectra of carboxypeptidase A (ZnCPD) show
      progressive spectral changes particularly in the near edge region when the pH is
      changed from neutral to alkaline values. Both least square fitting and radial
      distribution function (RDF) data analysis yield two distributions of atoms in the
      first coordination shell of ZnCPD at all pH values and at both 150 and 297 K.
      Direct comparison of the first and higher coordination shells of ZnCPD reveals
      structural differences between pH 7.0 and pH 9.9. At pH 7.0, the zinc ion has
      four ligand atoms (N or O) at an average distance of 2.024 +/- 0.006 A, and a
      smaller distribution of 1.3 atoms (N or O) at 2.54 +/- 0.05 A from the zinc ion
      (from the least square fitting analysis). At pH 9.9, the larger distribution
      contains four atoms at a 0.022 A shorter distance (2.002 A) from the zinc, while
      the smaller distribution contains 0.7 atoms at 2.52 +/- 0.06 A. The smaller
      distribution can be attributed mainly to the contribution of the epsilon 2-oxygen
      of Glu 72 and to the atoms farther away for which the contribution cannot be
      fully separated from the first shell peak. The structural changes of ZnCPD at
      intermediate pHs are consistent with the changes observed at pH 7.0 and pH 9.9.
      The XAFS Debye-Waller factor shows an increased structural disorder for the four
      atom distribution at the alkaline pH.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268160
TI  - Conformational distributions of a four-way DNA junction revealed by time-resolved
      fluorescence resonance energy transfer.
AB  - Conformational distributions of a four-way DNA junction have been examined by
      time-resolved fluorescence resonance energy transfer (FRET). A series of dye
      labeled junctions were synthesized with donor (fluorescein) and acceptor
      (tetramethylrhodamine) dyes conjugated to the 5' termini of the duplex arms in
      all six pairwise combinations. The fluorescence decay of the donor in each
      junction was measured by time-correlated single-photon counting. The
      distributions of donor-acceptor (D-A) distances present between each pair of arms
      were recovered from the donor decays using a continuous Gaussian distribution
      model. The overall geometry of the four-way junction defined by the six mean D-A
      distances was consistent with a stacked-X structure, wherein pairs of duplex arms
      associate to form two continuous domains. Large differences were observed in the
      widths of the D-A distance distributions, depending on which pair of arms were
      labeled with the donor and acceptor dyes. Distances measured along the stacking
      domains were characterized by relatively narrow distributions, indicating that
      these domains were rigid, whereas distances between stacking domains had broader
      distributions, reflecting variability in the angle between the two domains. The
      distances described by broad distributions were overestimated by steady-state
      FRET measurements. These results suggest that an ensemble of stacked-X structures
      are present in solution, characterized by differences in the small angle between
      the stacking domains. Temperature and solvent effects on the recovered
      distribution widths provide an indication of flexibility in the four-way
      junction.

PMID- 8268161
TI  - Effects of temperature on rhodopsin photointermediates from lumirhodopsin to
      metarhodopsin II.
AB  - Absorbance changes following the photolysis of mildly sonicated membrane
      suspensions of bovine rhodopsin are monitored using multichannel detection at 15,
      20, 25, 30, and 35 degrees C. Difference spectra collected with microsecond time
      resolution are analyzed by singular value decomposition and multiexponential
      fitting. Several kinetic schemes are tested using methods that compare the
      observed rates and associated spectral amplitudes to the eigenvalues and
      eigenvectors of kinetic matrices. The time evolution of the spectra is more
      complex than can be accounted for by the traditional lumi-->metarhodopsin I<-
      >metarhodopsin II scheme. Above 25 degrees C, the formation of metarhodopsin II
      is achieved without a large transient accumulation of metarhodopsin I. Within the
      framework of first-order kinetics, the observations are explained by simple
      kinetic schemes that lead to the formation of a deprotonated Schiff's base
      species temporally distinct from metarhodopsin II directly upon the decay of
      lumirhodopsin.

PMID- 8268162
TI  - Characterization of the cardiac troponin I phosphorylation domain by 31P nuclear
      magnetic resonance spectroscopy.
AB  - Cardiac holotroponin can be phosphorylated at serine 23 and/or 24 in the heart
      specific region of bovine troponin I. When isolated freshly it is composed of a
      mixture of non-, two mono-, and bisphosphorylated species. At neutral pH the
      monophosphorylated form carrying phosphate at serine 24 yields a resonance signal
      at 4.6 ppm and that carrying phosphate at serine 23 at 4.4 ppm; the two phosphate
      groups of the bisphosphorylated form yield only one 31P-NMR signal at 4.2 ppm.
      From the chemical shift dependence on pH, pKa values have been estimated to be
      5.3 and 5.6 for the phosphate groups at serine 24 and serine 23, respectively.
      Both phosphates of the bisphosphorylated form exhibit very similar pKa values of
      approximately 5.8. Separation of bisphosphotroponin I from the complex results in
      a downfield shift and the appearance of two 31P-NMR signals at positions
      comparable to those of the two monophospho forms. Complex formation of cardiac
      troponin I with C or T does not alter the spectrum obtained with isolated
      troponin I; however, the original troponin spectrum is restored by reconstitution
      of the holocomplex from all three components T, I, and C. Two signals are also
      observed with a bisphosphorylated synthetic peptide [PVRRRS(P)S(P)ANYR]
      representing the phosphorylation domain. pKa values of about 5.3 and 5.6 have
      been determined for serine 7 (corresponding to serine 24 of troponin I) and
      serine 6 of the peptide (corresponding to serine 23 of troponin I).

PMID- 8268163
TI  - Fourier transform infrared study of the primary electron donor in chromatophores
      of Rhodobacter sphaeroides with reaction centers genetically modified at residues
      M160 and L131.
AB  - Structural changes in chromatophores of Rhodobacter sphaeroides reaction center
      mutants associated with the substitution of amino acid residues near the primary
      electron donor P have been investigated by light-induced FTIR difference
      spectroscopy. The single-site mutations Leu-L131 to His and Leu-M160 to His and
      the corresponding double mutation were designed to introduce a proton-donating
      residue that could form a hydrogen bond with the keto carbonyl of ring V of each
      bacteriochlorophyll (PL and PM) of the dimer. The presence of large positive
      bands at approximately 1550, 1480, and 1295 cm-1, as well as at 2600-2800 cm-1 in
      the light-induced P+QA-/PQA FTIR difference spectra, corresponding to the
      photooxidation of P and the photoreduction of the primary quinone QA,
      demonstrates that the BChl dimer state of P+ is preserved in the LH(L131),
      LH(M160), and LH(M160)+LH(L131) mutants, although frequency shifts and amplitude
      changes can be observed, notably for LH(M160). Compared to wild type, these
      changes are thought to reflect a different charge repartition over the two BChls
      in P+. Large frequency downshifts in the 9-keto C=O stretching region of the P+QA
      /PQA FTIR difference spectra of chromatophores are observed in the mutant samples
      relative to wild type. For the LH(M160) mutant, a large differential signal at
      1678/1664 cm-1 is assigned to a shift, upon photooxidation, of the 9-keto C=O of
      PM hydrogen-bonded to His-M160, while that at 1718/1696 cm-1 corresponds to the
      free 9-keto C=O of PL.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268164
TI  - Human cobalophilin: the structure of bound methylcobalamin and a functional role
      in protecting methylcobalamin from photolysis.
AB  - The interactions of methylcobalamin with cobalophilin from human serum were
      analyzed using extended X-ray absorption fine structure (EXAFS) spectroscopy,
      photolysis of the cobalt-carbon bond of methylcobalamin, and a pKa determination
      of the protonation of the coordinated nitrogen of 5,6-dimethylbenzimidazole
      (DMB). These results are consistent with the idea that the DMB nitrogen is still
      coordinated when protein is bound; however, the ability of a methyl radical
      (generated by photolysis) to escape the geminate cage of the protein is
      considerably reduced. For methylcobalamin in solution, the DMB nitrogen ligand is
      at a distance of 2.20 +/- 0.03 A from cobalt [Sagi, I., & Chance, M. R. (1992) J.
      Am. Chem. Soc. 114, 8061-8066]. This distance to the lower axial ligand does not
      change when protein binds (2.20 +/- 0.04 A), nor do the optical spectra exhibit
      any base-off character. The average of the distance from cobalt to the four
      equatorial nitrogens of the corrin plane is also unchanged. The pKa for the
      conversion of the "base-on" to the "base-off" form of methylcobalamin, where the
      above DMB nitrogen becomes protonated and the Co-N axial bond is cleaved, does
      not deviate from the free cobalamin value of 2.7 when methylcobalamin is bound to
      cobalophilin. These results indicate that replacement of the DMB ligand with a
      ligand from the protein is unlikely. Although the background-subtracted EXAFS
      data sets for free methylcobalamin and for the protein complex are extremely
      similar, more accurate data with explicit higher shell analysis would be required
      to entirely rule out ligand replacement. The chemical and electronic nature of
      the ligand changes little.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268165
TI  - Use of polymerized mixed liposomes to study interactions of phospholipase A2 with
      membranes.
AB  - Polymerized liposomes of thiol-based phospholipids, 1,2-bis[12
      (lipoyloxy)dodecanoyl]-sn-glycero-3-phosphocholine (BLPC) and -phosphoglycerol
      (BLPG) were used to study interactions of several phospholipases A2 (PLA2) with
      membranes. Large liposomes (an average diameter of 100 +/- 10 nm) prepared from
      BLPC or BLPG were readily hydrolyzed by PLA2. Once polymerized, however, these
      liposomes were resistant to the PLA2 hydrolysis. When liposomes were prepared
      from a mixture of 1-hexadecanoyl-2-(1-pyrenyldecanoyl)-sn-glycero-3
      phosphocholine (pyrene-PC) (5 mol%) and BLPC, fluorescence measurements of
      resulting polymerized mixed liposomes showed that the pyrene-PC molecules exist
      solely as monomers without forming a patch and were selectively hydrolyzed by
      PLA2. Progress of the hydrolysis can be readily monitored by measuring the change
      in fluorescence emission at 380 nm in the presence of bovine serum albumin. Rapid
      and selective hydrolysis of inserted phospholipids in polymerized mixed liposomes
      supports the notion that facile migration of a phospholipid substrate from
      membrane to the active site of enzyme is a critical step in the catalysis of
      PLA2. On the basis of these findings, various combinations of polymerized mixed
      liposomes were prepared and their hydrolysis by PLA2 measured. When compared to
      the substrate specificity of PLA2s determined using Triton X-100/phospholipid
      mixed micelles, results from polymerized mixed liposomes indicate that
      electrostatic interactions between the interfacial binding site of PLA2 and
      membrane surfaces play an important role in the determination of substrate
      specificity of PLA2 and in the regulation of PLA2 activities.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8268166
TI  - Contribution of long-range electrostatic interactions to the stabilization of the
      catalytic transition state of the serine protease subtilisin BPN'.
AB  - The possible role of long-range electrostatic interactions on the catalytic
      activity of the serine protease subtilisin BPN' is investigated using protein
      engineering techniques. Charged residues on the surface of the enzyme some 13-15
      A from the active site were mutated to either neutral or oppositely charged
      residues. The effect of these mutations on the stability of a complex formed
      between subtilisin BPN' and Z-Ala-Ala-Pro-Phe-trifluoromethyl ketone, a
      transition-state inhibitor of the enzyme, was measured. The values of Ki for the
      complex between the trifluoromethyl ketone and wild-type and mutant subtilisins
      were used to study the possible contribution of long-range electrostatics in
      stabilizing the charge distribution in the complex and thus, by analogy, on the
      transition state of hydrolysis for subtilisin BPN'. Measurement of kon, koff, and
      Ki for the inhibition of wild-type and mutant subtilisins showed that charged
      mutations distant from the active site can affect koff and Ki but have little
      effect on kon. The experimental results show that there is a small, 0.10-0.46
      kcal mol-1, but significant contribution to the binding energy from distant
      surface charges, at low ionic strength. The experimental results were compared to
      theoretical results, calculated using the DelPhi program for different charge
      distributions in the complex. The experimental results were found to be most
      consistent with a complex in which an ion pair is formed between the protonated
      active site histidine and the ionized oxyanion. Both experimental and theoretical
      results suggest that long-range electrostatic interactions do play a role in
      stabilizing the transition-state complex formed between enzyme and
      inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268167
TI  - Time resolution of fluorescence changes observed in titrations of fluorescein 5'
      isothiocyanate-modified Na,K-ATPase with monovalent cations.
AB  - Equilibrium fluorometric titrations of fluorescein 5'-isothiocyanate-modified
      Na,K-ATPase with cations have usually been interpreted by assuming that an
      enhancement reports the conformational change from E2 to E1. We report time
      resolution of the fluorescence change into three phases when fluorophore-modified
      enzyme is mixed with the chloride salt of either sodium or choline in a stopped
      flow instrument. The first phase is an increase in fluorescence within the dead
      time of the instrument that is also observed when fluorescein 5'-isothiocyanate
      (FITC) reacted with lysine is substituted for fluorescein-labeled enzyme. The
      other two phases occur on millisecond and second time scales. Three phases are
      also observed when fluorophore-modified enzyme preincubated in KCl is mixed with
      NaCl, but in this case the slowest phase is absent when choline chloride replaces
      NaCl. The two faster effects in phases one and two can be eliminated either by
      controlling the ionic strength or by anti-fluorescein antibody. Labeling the
      enzyme with fluorescein 5'-isothiocyanate in the presence of its substrate,
      adenosine 5'-triphosphate, practically eliminates the slowest effect. These
      results demonstrate that fluorescein reports three events that occur on three
      different time scales. The fastest phase reports the ionic strength jump of
      unbound fluorophore. The intermediate phase reports the ionic strength jump of
      fluorescein at "antibody-accessible" sites [Abbott, A. J., Amler, E., & Ball, W.
      J., Jr. (1991) Biochemistry 30, 1692-1701]. Only the slowest phase reports the
      enzyme conformational change implicated in transport.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268168
TI  - Fluorescence lifetimes of the tryptophan residues in ornithine transcarbamoylase.
AB  - Multifrequency (2-230 MHz) phase-modulation fluorescence measurements and site
      directed mutagenesis have been employed to assign fluorescence lifetimes, quantum
      yields, and emission maxima to the four tryptophans in the enzyme ornithine
      transcarbamoylase from Escherichia coli (OTCase) (Trp-125, -92, -233, and -243).
      OTCase displays two apparent fluorescence lifetimes, 7.2 and 3.2 ns. Results on
      specific mutants show that Trp-233 has a lifetime of 7.1 ns, while TRP-125, -192,
      and -243 have lifetimes of 4.0, 3.6, and 4.9 ns, respectively. Thus, the specific
      conformational changes of the polypeptide segment involving Trp-233 may be
      monitored conveniently in the wild-type enzyme. On the basis of quantum yield
      values, Trp-233 is calculated to contribute approximately 43% of the fluorescence
      intensity of the enzyme, while direct measurements of the enzyme show that up to
      65% of the total intensity is really emitted by this tryptophan. The discrepancy
      may arise from energy transfer from Trp-125 to Trp-233, with an efficiency of
      20%. Application of the assigned tryptophan lifetimes to probe ligand-induced
      protein conformational changes has also been demonstrated.

PMID- 8268169
TI  - Kinetics of assembly and dissociation of the mitochondrial creatine kinase
      octamer. A fluorescence study.
AB  - The dissociation of octameric mitochondrial creatine kinase (Mi-CK) into dimers
      induced by the transition-state analogue complex (TSAC) mixture
      (creatine+Mg(2+)+ADP+NO3-) is accompanied by a large (25.2%) decrease in Trp
      fluorescence. This effect is caused by a Trp residue situated at the dimer-dimer
      interface within the octamer, which becomes susceptible to solvent quenching upon
      octamer dissociation. Octamer formation, induced by adding excess EDTA to TSAC
      dissociated Mi-CK, involves a transient tetrameric species, whereas the
      dissociation reaction proceeds in a one-step, all-or-none fashion. From
      fluorescence spectroscopic investigations of the octamer formation and
      dissociation reactions, a first-order dissociation rate constant of 0.19 min-1
      and a bimolecular association rate constant of 318 M-1 s-1 at 30 degrees C were
      obtained. The octamers formed after EDTA addition can be dissociated again by
      lowering the temperature to 4 degrees C, indicating a substantial hydrophobic
      contribution to the interactions stabilizing the octamer.

PMID- 8268170
TI  - Physical characterization of a reactivatable liposome-bound rhodanese folding
      intermediate.
AB  - Recently, we described the formation of a complex between liposomes and the
      unfolded protein rhodanese (thiosulfate:cyanide sulfurtransferase, EC 2.8.1.1),
      which could be liberated and efficiently reactivated after treatment of the
      complex with detergents [Zardeneta, G., & Horowitz, P. M. (1992) Eur. J. Biochem.
      210, 831-837]. Previous data suggested that liposome-bound rhodanese was in the
      form of a folding intermediate. We have characterized in greater detail the
      nature of the conformation of the bound rhodanese. Physical characterization of
      the bound rhodanese intermediate was carried out using proteolysis, fluorescence
      studies with 1,8-anilinonapthalene-8-sulfonic acid, a probe for hydrophobic site
      exposure, intrinsic fluorescence to determine tryptophan accessibility using the
      quenchers acrylamide and iodide, and circular dichroism to detect extent of
      secondary structure. These studies show that the rhodanese intermediates bound to
      either cardiolipin or phosphatidylserine liposomes are not identical, the former
      being in a less compact conformation yet having more secondary structure than the
      latter, an observation which may explain why the reactivation of the former
      intermediate is more effective. Finally, turbidimetric and proteolytic studies
      raise the possibility that each rhodanese intermediate binds to several
      liposomes. This finding suggests that a possible reason for the differential
      reactivation yields obtained may be due to the fact that unfolded rhodanese has
      more binding sites for cardiolipin than for phosphatidylserine liposomes. A
      greater number of binding sites would result in better anchoring of rhodanese's
      interactive surfaces and thus reduce the likelihood of misfolding.

PMID- 8268171
TI  - Synthesis and characterization of wild-type and variant gamma-carboxyglutamic
      acid-containing domains of factor VII.
AB  - Synthetic peptides corresponding to portions of the wild-type and variant
      sequences of the human factor VII gamma-carboxyglutamic acid (Gla)-containing
      domain have been prepared by direct peptide synthesis using the Fmoc-based
      protection strategy. Peptides were purified by ion-exchange and reversed-phase
      chromatography and characterized as the correct products. A peptide comprising
      residues 1-49 (GP 1-49) inhibited the activation of factor X (FX) by soluble
      tissue factor (sTF) and recombinant activated factor VII (rFVIIa). In the absence
      of phospholipid, no inhibition by this peptide was observed. GP 1-49 did not
      inhibit the hydrolysis of a peptidyl substrate by rFVIIa in the presence of
      either sTF or relipidated TF apoprotein in the presence or absence of
      phospholipid. A similar peptide (residues 1-38, GP 1-38) that did not contain the
      aromatic stack region was also inhibitory. Two variant peptides, one identical to
      GP 1-49 but lacking the N-terminal alanine residue (GP 2-49) and one identical to
      GP 1-38 but with an arginine to alanine substitution at position 9 (GP 1-38 R9A),
      showed substantially reduced inhibitory activity. Kinetic analysis of the
      inhibition of Xa generation by GP 1-49 revealed a noncompetitive mode of
      inhibition, probably via a substrate-depletion mechanism. GP 1-49 does not
      inhibit by preventing FX binding to phospholipid surfaces. This indicates that
      the N-terminal residues of the FVII Gla domain are important for the structural
      integrity of the peptide, and implicates the Gla domain per se in a direct
      interaction with phospholipid-bound FX.

PMID- 8268172
TI  - Structure of the 265-kilodalton complex formed upon EDC cross-linking of
      subfragment 1 to F-actin.
AB  - The conventional model of force generation in muscle requires the presence of at
      least two different contact areas between the myosin head (S1) and the actin
      filament. It has been found that S1 has two sites available for carbodiimide
      cross-linking, but it is generally believed that the myosin head can be cross
      linked to only one actin through either site. We provide here, for the first
      time, evidence that one S1 can be cross-linked to two separate actin molecules.
      The covalent complex of one S1 with two actins was found to have an apparent
      molecular mass of 265 kDa. The formation of the 265-kDa acto-S1 complex was
      strongly dependent on the ratio of S1 to actin. Limited tryptic digestion
      converted the 265-kDa product into the 240-kDa complex by releasing a 27-kDa N
      terminal S1 fragment. Limited subtilisin digestion of the 265-kDa covalent acto
      S1 complex yielded 29-, 93-, and 66-kDa peptides which corresponded to the 29-kDa
      N-terminal domain of S1, actin-44-kDa (central domain of S1) and actin-22-kDa (C
      terminal domain of S1) complexes, respectively. These peptides could be generated
      only if a single S1 has been cross-linked to two separate actins. The 265-kDa
      acto-S1 complex (S1:actin ratio = 0.5) had 60% of the ATPase activity of the 175
      185-kDa acto-S1 complex (S1:actin ratio = 1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268173
TI  - A multinuclear NMR study of the affinity maturation of anti-NP mouse monoclonal
      antibodies: comparison of antibody combining sites of primary response antibody
      N1G9 and secondary response antibody 3B62.
AB  - On the basis of multinuclear NMR data, the structures of the antibody combining
      sites of anti-4-hydroxy-3-nitrophenylacetyl (NP) antibodies were compared for
      N1G9, which is one of the primary response antibodies with low affinity for NP,
      and 3B62, which is one of the secondary response antibodies with high affinity
      for NP. It has been concluded, on the basis of the results of antibody
      engineering, that in most secondary response antibodies a Trp-->Leu exchange at
      position 33 of the heavy chain is primarily responsible for the increased
      affinity for NP [Allen, D., Simon, T., Sablitzky, F., Rajewsky, K., & Cumano, A.
      (1988) EMBO J. 7, 1995-2001]. Although 3B62 exhibits one of the highest
      affinities for NP, it lacks the Trp-->Leu exchange at position 33 of the heavy
      chain. A variety of stable isotope-labeled Fab analogues of N1G9 and 3B62 have
      been prepared. Chain-specific resonance assignments were made by recombination of
      the heavy chains and light chains of the Fab fragments. Binding experiments of a
      spin-labeled hapten and NOESY experiments have demonstrated that, compared with
      the environment of the antibody combining site of N1G9, the combination of
      mutations (including one codon deletion) and the particular D-JH rearrangement in
      the heavy chain of 3B62 affords a more hydrophobic environment, which is formed
      by one Tyr residue originating from the light chain and two Tyr residues
      originating from the heavy chain.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268174
TI  - Peroxide dependence of the semisynthetic enzyme selenosubtilisin.
AB  - Selenosubtilisin, a semisynthetic enzyme produced by chemical modification of
      subtilisin's catalytic serine, mimics the antioxidant enzyme glutathione
      peroxidase, catalyzing the reduction of hydroperoxides by 3-carboxy-4
      nitrobenzenethiol. In analogy with the natural peroxidase, a variety of
      hydroperoxides are accepted as substrates for the semisynthetic enzyme, whereas
      the dialkyl compound tert-butyl peroxide is not. Kinetic investigations reveal
      that kmax is dependent upon the nature of the hydroperoxide, indicating that
      peroxide-mediated oxidation of the enzymic selenolate is at least partially rate
      limiting. Experiments with the radical trap 2,6-di-tert-butyl-4-methylphenol
      suggest that, while the nonenzymic reaction between tert-butyl hydroperoxide and
      thiol involves free radicals, the same reaction catalyzed by selenosubtilisin
      does not. The studies described here support the enzyme's proposed ping-pong
      mechanism and are consistent with previous mechanistic observations.

PMID- 8268175
TI  - Isolation and kinetic characterization of the calmodulin methyltransferase from
      sheep brain.
AB  - The methyltransferase that catalyzes the trimethylation of lysine 115 in
      calmodulin has been purified from sheep brain. The enzyme is a monomer with an
      apparent molecular weight of 38,000 on the basis of gel filtration chromatography
      and SDS-polyacrylamide electrophoresis. In the presence of calcium the
      methyltransferase exhibited a Km of 100 nM for unmethylated calmodulin and a kcat
      of 0.0278 s-1. The enzyme was able to use calcium-depleted calmodulin as a
      substrate, albeit with less efficiency. The methylation of calcium-depleted
      calmodulin was inhibited by increases in ionic strength, whereas methylation of
      calcium-saturated calmodulin was not affected. This suggests a difference in the
      mode of interaction of calcium-saturated and calcium-depleted calmodulins with
      the enzyme. As with calmodulin's interactions with other calmodulin-dependent
      enzymes, the oxidation of the methionines of calmodulin by performic acid
      treatment decreases the ability of the methyltransferase to recognize and
      methylate calmodulin. A calmodulin-binding peptide based on the calmodulin
      dependent protein kinase II sequence and the naphthalenesulfonamide W-7 inhibit
      the calmodulin methyltransferase-calmodulin interaction in a calcium-dependent
      manner. Removal of the NH2-terminal lobe (residues 1-77) does not affect the
      ability of the calmodulin methyltransferase to recognize and methylate lysine
      115. Thus, the determinants for calmodulin methyltransferase binding reside
      solely in the COOH-terminal lobe of calmodulin. Further, structural features
      within this region, in particular, the hydrophobic cleft, that are manifested
      upon calcium binding may contribute to the interaction of calmodulin with the
      enzyme.

PMID- 8268176
TI  - Urea-induced unfolding of the alpha subunit of tryptophan synthase: one
      dimensional proton NMR evidence for residual structure near histidine-92 at high
      denaturant concentration.
AB  - The urea-induced unfolding reaction of the alpha subunit of tryptophan synthase
      was monitored by examining the chemical shifts and peak areas of the C epsilon
      protons of the four histidine residues with 1D NMR spectroscopy. In a native base
      line region defined by tyrosine absorbance and far-UV circular dichroism
      spectroscopy, histidine-146 appears to undergo a rapid, local unfolding reaction
      at increasing denaturant concentrations. As the native form is converted to a
      previously detected stable intermediate between 2 and 3 M urea [Matthews, C. R.,
      & Crisanti, M. M. (1981) Biochemistry 20, 784], histidines-92 and -146 in the
      amino folding unit (residues 1-188) and histidines-195 and -244 in the carboxy
      folding unit (residues 189-268) all experience a change in their environments
      which is slow on the NMR time scale. The subsequent conversion of this
      intermediate to a newly detected, stable, partially folded form populated at 5 M
      urea appears to have no effect on any of the histidines at 25 degrees C when an
      intermolecular association process involving His-244 is taken into account.
      Strikingly, a slow exchange process involving only His-92 is observed to begin at
      5 M urea where the unfolding transitions monitored by absorbance or far-UV
      circular dichroism spectroscopy are essentially complete. This residual tertiary
      structure unfolds in a cooperative fashion as the urea concentration is increased
      to 8 M.

PMID- 8268177
TI  - Membrane-bound conformation of a signal peptide: a transferred nuclear Overhauser
      effect analysis.
AB  - We have determined the conformation of an analogue of the Escherichia coli LamB
      signal peptide inserted into a model membrane using the transferred nuclear
      Overhauser effect (trNOE) NMR technique. In order to make NMR analysis feasible,
      a water-soluble LamB signal peptide analogue was designed by inserting three
      basic residues (KRR) into the N-terminal region of the wild-type sequence (with a
      Val-->Trp mutation for fluorescence measurements), viz.,
      MMITLRKRRKLPLAVAVAAGWMSAQAMA-NH2. For the purpose of the trNOE study, the binding
      affinity of the peptide for phospholipid vesicles was tuned by adjusting the
      proportion of acidic lipid in the vesicle. Circular dichroism and fluorescence
      measurements showed that the KRR-LamB signal peptide spontaneously inserted into
      the lipid bilayer with a conformational transition from a mostly random coil to a
      predominantly alpha-helical structure. The trNOE analysis revealed that the alpha
      helix extended from approximately the beginning of the hydrophobic core (residue
      Leu8) to the C-terminus. The continuity of the helix was somewhat disrupted at
      the end of the hydrophobic core (around residue Gly17). Furthermore, the
      topological arrangement of the peptide within the lipid bilayer was explored by
      NMR line broadening induced by a paramagnetic nitroxide-labeled lipid. The line
      broadening results demonstrated that the residues in the helical region are well
      integrated into the acyl chain region of the bilayer. The N-terminal part of the
      peptide showed many trNOEs, but without any indication of a helical conformation.
      The line-broadening analysis indicates that this part of the peptide primarily
      interacts with the membrane surface.

PMID- 8268178
TI  - Structural characterization of the trypsinized estrogen receptor.
AB  - Structural differences between the unoccupied and ligand-occupied rat uterine
      estrogen receptors (ERs) were investigated using partial proteolysis followed by
      immunoblotting, affinity labeling, and gel filtration chromatography. Trypsin
      digestion of the unoccupied ER at 4 degrees C resulted in retention of 70-80% of
      high-affinity [3H]estradiol binding. Only two fragments of the rat ER were
      detected after prolonged trypsin treatment of the unoccupied ER followed by
      affinity labeling with [3H]tamoxifen aziridine. One fragment represents the
      intact steroid binding domain (28 kDa), and the other fragment is about 10 kDa.
      The small 10-kDa fragment of the ER detected by denaturing gel electrophoresis is
      shown to be held in a large oligomeric complex in solution using gel filtration
      chromatography. This oligomeric complex probably represents the steroid binding
      domain, which has its tertiary structure maintained predominantly by noncovalent
      interactions between the trypsin-generated fragments. The estrogen, anti
      estrogen, and unoccupied trypsinized ERs all result in similar patterns of
      fragments after separation by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and detection by immunoblotting. Although no new trypsin cleavage
      sites were exposed, the sensitivity of the available trypsin sites was altered by
      heating the ER and, to a lesser extent, by hormone treatment. Gel filtration
      chromatography of the trypsinized estradiol- and 4-hydroxytamoxifen-occupied ERs
      demonstrates similar, diffuse peaks centered at about the correct size for the
      intact steroid binding domain (28 kDa), whereas the trypsinized unoccupied ER
      results in a sharp, discrete peak centered at about 80 kDa.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8268179
TI  - The adenosine 5',5"',P1,P4-tetraphosphate receptor is at the cell surface of
      heart cells.
AB  - We have previously demonstrated the existence of an adenosine 5',5"',P1,P4
      tetraphosphate (Ap4A) receptor in mouse hart membrane fractions [Hilderman, R.
      H., Martin, M., Zimmerman, J. K., & Pivorun, E. P. (1991) J. Biol. Chem. 266,
      6915-6918]. However, we did not determine the cellular localization or
      distribution of the receptor. In this report, the Ap4A receptor is shown to be on
      the cell surface of individual mouse heart cells by the following four methods:
      (1) intact cells show specific, saturable, and reversible binding of Ap4A; (2)
      monoclonal antibodies (Mabs) raised against the Ap4A receptor inhibit Ap4A
      binding to its receptor on intact heart cells; (3) bound Mabs are shown to be at
      the outer cell surface via reaction with a alkaline phosphatase conjugated goat
      anti-rat IgG; (4) when intact cells are labeled with the impermeable cell surface
      labeling reagent, (sulfosuccinimido) biotin, labeled receptor is
      immunoprecipitated with Mabs. Furthermore, subcellular fractionation of mouse
      hearts demonstrates that virtually all of the Ap4A receptor is associated with a
      membrane fraction with at least 77% of the active receptor on plasma membranes.

PMID- 8268180
TI  - Physiological inhibitors of the catalytic subunit of cAMP-dependent protein
      kinase: effect of MgATP on protein-protein interactions.
AB  - The catalytic (C) subunit of cAMP-dependent protein kinase interacts with two
      classes of inhibitors. The regulatory (R) subunits, types I and II, associate to
      form an inactive holoenzyme complex that is activated in response to cAMP. The C
      subunit is also inhibited by small heat-stable protein kinase inhibitors (PKI's).
      Inhibition by both PKI and RI-subunit requires the synergistic high-affinity
      binding of MgATP. The stabilizing effect of ATP was quantitated by using
      analytical gel chromatography. Both the type I holoenzyme and the C.PKI complex
      in the presence of MgATP show apparent Kd's for subunit association that are
      below 0.1 nM, while in the absence of MgATP the apparent Kd's are 125 nM and 2.3
      microM, respectively, for the two complexes. In the absence of MgATP both
      complexes also can be dissociated readily and, hence, activated by salt-induced
      dissociation. Under physiological salt concentrations, salt-induced dissociation
      would be substantial in the absence of the high-affinity binding of MgATP. In
      both complexes, the ATPase activity of the free C-subunit is abolished. The off
      rates for MgATP also indicate that the type I holoenzyme is more stable than the
      C.PKI complex. The off rate (t1/2) for MgATP from the C.PKI complex is 17 min,
      while the off rate for the type I holoenzyme is 11.7 h. When the C.PKI complex is
      incubated with RI-subunit in the presence or absence of MgATP, the C-subunit
      preferentially reassociates with the RI-subunit, forming holoenzyme. In contrast,
      free PKI cannot compete for the C-subunit when it is part of a holoenzyme
      complex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268181
TI  - A non-heme iron protein with heme tendencies: an investigation of the substrate
      specificity of thymine hydroxylase.
AB  - Thymine hydroxylase from Rhodotorula glutinis catalyzes the oxidation of thymine
      to its alcohol, aldehyde, and carboxylic acid in three successive reactions. Each
      step involves stoichiometric consumption of O2 and alpha-ketoglutarate and
      formation of CO2 and succinate. Given the promiscuity of this enzyme, it was
      hoped that it would serve as a prototype for understanding the mechanism of this
      class of enzymes, the non-heme Fe2+ dioxygenases. Kinetic parameters for thymine,
      O2, Fe2+, and alpha-ketoglutarate have been determined, and isotope effect
      analysis of (trideuteriomethyl)thymine with enzyme reveals D(V) = 2.08 and D(V/K)
      = 1.11 at saturating O2. The kinetic parameters for (hydroxymethyl)uracil
      oxidation have been determined, and incubation of (5'-R)- and (5'-S)-[5'-2H]-5
      (hydroxymethyl)uracil with enzyme reveals stereospecific removal of the pro-S
      hydrogen. No apparent isotope effect is observed in this reaction. The substrate
      specificity of this enzyme has been examined in detail. The enzyme can catalyze
      epoxidation, oxidation of a thioether to a sulfoxide and a sulfone, hydroxylation
      of an unactivated carbon-hydrogen bond, and oxidation of a methylamine to
      formaldehyde, as revealed through studies with 5-vinyluracil, 5
      (methylthio)uracil, 5,6-dihydrothymine, and 1-methylthymine, respectively. In
      each case, the products were identified by gas chromatography-mass spectrometry,
      and 18O2-labeling studies revealed that one atom from O2 is incorporated into
      each product. The enzyme has also been shown to catalyze an uncoupling of
      hydroxylation and decarboxylation in the presence of a substrate analog incapable
      of undergoing hydroxylation or a substrate that is difficult to oxidize.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8268182
TI  - Mechanism-based inactivation of thymine hydroxylase, an alpha-ketoglutarate
      dependent dioxygenase, by 5-ethynyluracil.
AB  - 5-Ethynyluracil was shown to be a mechanism-based inactivator of thymine 7
      hydroxylase, with Ki = 22 microM and a k2 = 2.6 min-1l Inactivation resulted in
      covalent modification of the enzyme with a stoichiometry of approximately 1
      adduct/enzyme molecule. The reaction of thymine 7-hydroxylase with 5
      ethynyluracil also generated two products: 5-carboxyuracil and uracil-5
      acetylglycine. The enzyme adduct was stable at pH 2, 8, and 10 and stable to
      treatment with hydroxylamine. Following trypsin digestion of labeled enzyme, two
      labeled peptides corresponding to 45% of the adduct were isolated and sequenced.
      The results demonstrated the presence of a single modified amino acid. Tandem
      mass spectrometry suggested that the modified amino acid is tyrosine, which is
      linked to the inhibitor in an unprecedented fashion.

PMID- 8268183
TI  - Solid-phase synthesis of oligonucleotides containing site-specific N-(2'
      deoxyguanosin-8-yl)-2-(acetylamino)fluorene adducts using 9
      fluorenylmethoxycarbonyl as the base-protecting group.
AB  - Eight oligodeoxyribonucleotides containing a site-specific N-(2'-deoxyguanosin-8
      yl)-2-(acetyl-amino)fluorene (dG-C8-AAF) adduct were prepared successfully by
      solid-phase DNA synthesis using the 2-cyanoethyl N,N-diisopropylphosphoramidites
      of dA, dC, dG, dT, and dG-C8-AAF, with 9-fluorenyl-methoxycarbonyl (Fmoc) as the
      base-protecting group. The oligonucleotides were deprotected and released from
      the support by 1:9 piperidine/MeOH at room temperature for 22-36 h or by 1:1
      diisopropylamine in MeOH at 55 degrees C for 15 h, purified by HPLC, and fully
      characterized. About 6 mg of HPLC-purified d[GTGGCG(C8-AAF)CCAAGT] and 7 mg of
      d[GTGATG(C8-AAF)ATAAGT] were obtained from the 10-mumol-scale synthesis, and
      their 1D 1H NMR spectra were consistent with the presence of a dG-C8-AAF adduct.
      The dG-C8-AAF oligonucleotides were also deacetylated to afford the corresponding
      dG-C8-AF oligonucleotides. d[GTGGCG(C8-AAF)CCAAGT] formed stable 1:1 duplexes
      with both the fully complementary 12-mer and a GC-deleted (across the adduct) 10
      mer complement, and identical melting temperatures were observed for both
      duplexes. The multidimensional NMR study of these duplexes is presently under
      investigation.

PMID- 8268184
TI  - Triple aminoacylation specificity of a chimerized transfer RNA.
AB  - We report here the rational design and construction of a chimerized transfer RNA
      with tripartite aminoacylation specificity. A yeast aspartic acid specific tRNA
      was transformed into a highly efficient acceptor of alanine and phenylalanine and
      a moderate acceptor of valine. The transformation was guided by available
      knowledge of the requirements for aminoacylation by each of the three amino acids
      and was achieved by iterative changes in the local sequence context and the
      structural framework of the variable loop and the two variable regions of the
      dihydrouridine loop. The changes introduced to confer efficient acceptance of the
      three amino acids eliminate aminoacylation with aspartate. The interplay of
      determinants and antideterminants for different specific aminoacylations, and the
      constraints imposed by the structural framework, suggest that a tRNA with an
      appreciable capacity for more than three efficient aminoacylations may be
      inherently difficult to achieve.

PMID- 8268185
TI  - Self-splicing of the Tetrahymena pre-rRNA is decreased by misfolding during
      transcription.
AB  - RNA processing depends in part on the ability of nascent transcripts to fold into
      the desired conformation. Self-splicing of the group I intron from Tetrahymena
      was used to assess the folded state of preribosomal RNA transcripts when
      synthesized in vitro. A simple method for isolating nondenatured RNA from a T7
      RNA polymerase reaction was tested. The intron alone is fully active when
      transcribed at 30 degrees C, suggesting that the active structure is both
      kinetically and thermodynamically favored. Longer precursor RNAs, however, were
      less than completely active in self-splicing. Full activity, as judged by both
      the initial rate and the extent of product formation, was restored by brief
      incubation at 95 degrees C and rapid cooling in the presence of magnesium ion.
      This result did not depend on the length of the precursor RNA in any simple way,
      but correlated loosely with the presence of intact exon domains. When transcribed
      in the absence of cellular proteins, a significant portion of the pre-RNA appears
      to be trapped in a conformation that does not readily undergo the first step of
      splicing.

PMID- 8268186
TI  - Selectivity of polyamines in triplex DNA stabilization.
AB  - Triplex DNA has been recently studied as an anti-gene strategy to suppress the
      transcription of specific genes. A major challenge in this area is to stabilize
      triplex DNA at physiological conditions. We studied the effects of putrescine,
      spermidine, spermine, their synthetic homologs, and their acetyl derivatives on
      triple- and double-stranded structures formed from poly(dA) and poly(dT) by
      measuring their respective melting temperatures. In the presence of polyamines,
      the absorbance (A) versus temperature (T) profile showed two transitions: Tm1,
      corresponding to triplex-->duplex+single-stranded DNA, and Tm2, corresponding to
      duplex melting. In the presence of 0.5 mM putrescine, Tm1 and Tm2 were 44.8 and
      71 degrees C, respectively, in 10 mM sodium cacodylate buffer (pH 7.2). In
      contrast, triplex DNA was not detectable when the A versus T profile of the
      polynucleotides was monitored in the absence of putrescine. Tm2 was also lower
      (55 degrees C) in the absence of putrescine. With 2.5 microM spermidine or 0.1
      microM spermine, Tm1 values were 42.8 and 54.4 degrees C and Tm2 values were 65
      and 82 degrees C, respectively. As the concentration of polyamine was increased,
      the difference between Tm1 and Tm2 decreased, and both melting transitions merged
      into one Tm, corresponding to the melting of triplex DNA to single strands. In a
      series of putrescine homologs, H2N (CH2)nNH2 where n = 2-6 (n = 4 for
      putrescine), H2N(CH2)3NH2 was the most effective diamine to stabilize the
      poly(dA).2poly(dT) triplex. At 10 mM concentration, diaminopropane stabilized the
      triplex DNA such that the Tm1 was 10 degrees C higher than that in the presence
      of an equimolar concentration of putrescine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268187
TI  - TGF-beta receptors: a complicated system of multiple binding proteins.

PMID- 8268188
TI  - Wilms tumor genes.
AB  - Multiple 'WT' genes exist. The WT1 gene at chromosomal band 11p13 has been cloned
      and is known to be important in the etiology of at least some tumors by virtue of
      the identification of both germline and somatic mutations in WT patients. Genes
      at 11p15 and 16q are also involved, either as initiating or tumor progression
      events. An unlocalized familial predisposition gene is also known to be important
      etiologically. The identification of several genes that are involved in the
      etiology or progression of WT, the preferential loss of maternally derived
      alleles in tumor tissue, and the observed reduction to 11p homozygosity in normal
      tissue DNA from some patients, all strikingly indicate that a simple, one-locus
      'two-hit' genetic model for WT is inadequate. The question is not if this model
      needs to be modified, but how it should be modified, or if it is even valid
      enough to be a starting point for understanding the genetics of Wilms tumor. To
      begin to address this, several questions can be asked. Do all Wilms tumors carry
      mutations at the WT1 locus? Do both alleles at the WT1 locus need to be
      inactivated or lost for tumorigenesis? Or, instead, do some WT1 mutations act
      dominantly? Do patients with bilateral disease carry germline mutations as
      originally hypothesized, or, as more recently suggested, is bilateral disease the
      result of early somatic mutations, genomic imprinting, or multifactorial
      inheritance? Must mutations at an 11p15 locus and/or 11p15 LOH accompany WT1
      mutations, or do 11p13 and 11p15 mutations act independently of each other? Have
      tumors from familial WT cases (who do not carry germline WT1 mutations) sustained
      somatic mutations at the WT1 locus, the 11p15 locus or the 16q locus? Conversely,
      do tumors from sporadic WT patients carry somatic mutations at the non-11p
      familial predisposition gene? Will most tumors be found to carry mutations at the
      same one or two loci, but differ only with regard to whether the mutations are
      somatic or germline? Are effects of genomic imprinting layered over, so to speak,
      a framework of classically mendelian mutations, or in some cases is imprinting
      the mechanism by which genes are inactivated or their normal function modulated?
      Although not definitive, there are data that bear on some of these questions.
      Germline mutations have been observed in patients with bilateral tumors, but may
      not prove to be a universal feature of bilateral disease.(ABSTRACT TRUNCATED AT
      400 WORDS)

PMID- 8268189
TI  - Interaction of tyrosine kinase oncoproteins with cellular membranes.

PMID- 8268190
TI  - Cellular transformation by papillomavirus oncoproteins.

PMID- 8268191
TI  - Gene regulation by Ets proteins.

PMID- 8268192
TI  - Hepatocyte growth factor/scatter factor and its receptor, the c-met proto
      oncogene product.

PMID- 8268193
TI  - Proton translocation mechanism and energetics in the light-driven pump
      bacteriorhodopsin.
AB  - In spite of many still unsolved problems, the mechanism and energetics of the
      light-driven proton transport are now basically understood. Energy captured
      during photoexcitation, and retained in the form of bond rotations and strains of
      the retinal, is transformed into directed changes in the pKa values of
      vectorially arranged proton transfer groups. The framework for the spatial and
      temporal organization of these changes is provided by the protein near the
      retinal Schiff base. The transport is completed by proton transfer among three
      essential groups in three domains lying roughly parallel with the membrane plane
      (Fig. 1): (a) the anionic D85 that is included in a complex of residues on the
      extracellular side containing also R82, D212, Y57 and bound water; (b) the
      protonated Schiff base; and (c) the protonated D96 that is included in a complex
      of residues on the cytoplasmic side containing also R227, T46, S226, and bound
      water. Other neighboring polar groups and water bound elsewhere which play a role
      in the transport do so either by further influencing the pKa values of the three
      protonable groups, or by providing passive pathways for proton transfer. The
      Schiff base proton, destabilized after photoexcitation, is transferred to the low
      pKa group D85 located on the extracellular side. The access of the deprotonated
      Schiff base then changes to the cytoplasmic side (the 'reprotonation switch') and
      its proton affinity increases. Finally, the proton of the high pKa group D96,
      with access to the cytoplasmic side, is destabilized by a protein conformational
      change through rearrangement of R227, T46, S226 and bound water, and becomes
      transferred to the Schiff base. As shown schematically in Fig. 3, these internal
      events are coupled to proton release and uptake at the two aqueous surfaces. The
      charge of the extracellular hydrogen-bonded complex is redistributed upon
      protonation of D85, and if the pH is above the pKa of the complex a proton is
      released to the bulk. After reprotonation of the Schiff base the pKa of the
      cytoplasmic hydrogen-bonded complex is raised well above the pH, and D96 regains
      a proton from the bulk. If the pH is lower than the pKa of the extracellular
      complex the proton release is delayed until the end of the photocycle. In either
      sequence there is net transfer of a proton from the cytoplasmic to the
      extracellular phase. The transfer of excess free energy from the chromophore to
      the protein, and finally to the transported proton, is described by a
      characteristic thermodynamic cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8268194
TI  - The relationship between the capacity to evolve oxygen and the variable
      fluorescence of chlorophyll after microsecond illumination in Chlorella, pea
      leaves and pea thylakoids.
AB  - The relationship between the capacity to evolve oxygen following a flash of a few
      microseconds duration and the variable fluorescence of chlorophyll was determined
      in Chlorella, leaf disks of peas, and thylakoids of pea leaves. It was found that
      this relationship is linear in intact plant material, while it is nonlinear in
      thylakoids. However, in thylakoids, the recovery of the capacity to evolve oxygen
      does not track the decay of the variable yield of Chl a fluorescence. This
      nonlinear relationship in thylakoids results from a reduced rate in the oxygen
      evolution reaction with no change in the decay of the variable yield of Chl a
      fluorescence. From a new application of the matrix analysis method to oxygen
      flash yields, the S1'-->S2, S2'-->S3 and S3'-->S4-->S0 transitions are found to
      be slowed or delayed in pea thylakoids and this underlies the slower rate of the
      recovery of the capacity to evolve oxygen in thylakoids. It is concluded that in
      intact cells the QA-QB(-)-->QA QB- reaction was rate-limiting for the recovery of
      the capacity to evolve oxygen, the equal energy-transfer hypothesis and the
      sequential double-hit model are valid in pea leaves and that the apparent
      invalidity in thylakoids is actually due to slowing of reaction steps in the
      oxygen evolution mechanism.

PMID- 8268195
TI  - Oxidative turnover increases the rate constant and extent of intramolecular
      electron transfer in the multicopper enzymes, ascorbate oxidase and laccase.
AB  - Using laser flash photolysis of lumiflavin/EDTA solutions containing ascorbate
      oxidase, we find that the rate constant for intramolecular electron transfer
      varies from one enzyme preparation to another and is generally a more sensitive
      measure of the state of the active site than are steady-state assays. Thus, type
      I copper is initially reduced in a second-order reaction followed by first-order
      reoxidation by the type II-III trinuclear copper center. The observed rate
      constant for this intramolecular process in presumably native enzyme is 160 s-1
      at pH 7, whereas an enzyme preparation which had less than 20% activity had a
      rate constant of 2.6 s-1. Other samples of relatively active enzyme showed
      biphasic intramolecular kinetics intermediate between the above values. The
      inactive enzyme sample could be reactivated by dialysis against ascorbate or by
      treatment with ferricyanide, resulting in a corresponding increase in the
      intramolecular rate constant for type I copper reoxidation to a value comparable
      to that of native enzyme. Using this same methodology, we have determined that
      the type I copper in Japanese lacquer tree laccase is reoxidized by the type II
      III trinuclear copper center in a first-order (intramolecular) process with rate
      constants of 1 s-1 at pH 7.0 and 4.9 s-1 at pH 6.0, values which are
      approximately two orders of magnitude smaller than for ascorbate oxidase. The
      intramolecular rate constant and enzyme activity for laccase also increased, but
      only by a factor of 2-6, when the enzyme was treated with ascorbate or
      ferricyanide, respectively. We further found that intramolecular electron
      transfer in laccase was completely inhibited by fluoride ion, in contrast to
      ascorbate oxidase which is unaffected by this ion. These differences in behavior
      for these two very similar enzymes are rather remarkable, when it is considered
      that the distance between copper atoms is constrained by the location of the
      protein-derived copper ligands in the three-dimensional structure, and that the
      redox potentials of the enzymes are similar. Our results may be interpreted in
      terms of an interconversion between active and inactive enzyme in which there is
      a rearrangement of the type II-III trinuclear copper center, resulting in a
      lowering of the redox potential and a block in electron transfer. Turnover
      restores the active enzyme conformation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8268196
TI  - Bacteriochlorophyll aggregates in positively charged micelles.
AB  - Micellar complexes were prepared from bacteriochlorophyll a and
      bacteriopheophytin a with the cationic detergents, cetyltrimethyl ammonium
      bromide and cetylpyridinium chloride. These complexes have spectroscopic
      properties (absorption, circular dichroism) which are very different from the
      ones formed with non-ionic detergents like Triton X-100, and also with anionic
      detergents. Bacteriochlorophyll a forms two complexes: One is blue-shifted and
      has excitonically coupled Qy transitions. The second one is extremely red
      shifted. The unusual properties are suggested to result from interactions of the
      positively charged head-group of the detergent with the tetrapyrrole.

PMID- 8268197
TI  - Association of the mcrD gene product with methyl coenzyme M reductase in
      Methanococcus vannielii.
AB  - The mcrD gene, subcloned from the methyl coenzyme M reductase (MR) encoding
      mcrBDCGA operon in Methanococcus vannielii, has been expressed at a high level in
      Escherichia coli. Rabbit antibodies, raised against the product of this gene
      (rgpmcrD, recombinant gene product of mcrD) purified from E. coli, have been used
      to quantitate gpmcrD in M. vannielii and to follow its fate during MR
      purification. The molar ratio of gpmcrD to MR was found to be approx. 1:15 in
      cells of M. vannielii taken from batch cultures at all stages of growth.
      Sedimentation of lysates of M. vannielii cells through sucrose gradients and
      analyses of the fractions obtained by Western blotting and immunoprecipitation
      have demonstrated the presence of a macromolecular complex containing both gpmcrD
      and MR. Addition of mcrD antibodies or removal of gpmcrD from lysates of M.
      vannielii cells by immunoprecipitation decreased the rates of methanogenesis in
      vitro by approx. 20%. Addition of purified rgpmcrD to these lysates did not
      stimulate methanogenesis.

PMID- 8268198
TI  - Twin plastocyanin dimorphism in tobacco.
AB  - Two iso-plastocyanin fractions, oxidized b-plastocyanin, PCb(II) and reduced a
      plastocyanin, PCa(I), have been isolated from whole tobacco leaves by
      conventional chromatography on DEAE-cellulose. The isoelectric points of PCa and
      PCb at 10 degrees C were found to be 3.99 and 3.97, respectively. When the
      primary structures were analysed, a microheterogeneity within both PCa and PCb
      was observed. By appropriate peptide arrangements the amino-acid sequences of two
      PCa (PCa' and PCa") and two PCb (PCb' and PCb") have been differentiated. All
      four sequences contain 99 amino-acid residues. PCa' and PCa" differ in one
      position, where Ser-58 in PCa' is replaced by Pro in PCa".PCb' and PCb" differ in
      three positions, where Gly-65, Thr-81 and Ala-85 in PCb' are replaced by Ala, Ser
      and Ser in PCb", respectively. PCa (PCa'/PCa") generally differs from PCb
      (PCb'/PCb") in three positions, where Val-52, Glu-61 and Tyr-62 in PCa'/PCa" are
      replaced by Ala, Asp and Leu in PCb'/PCb", respectively. Fluorescence spectra of
      oxidized tobacco PCa and PCb have been characterized with an emission-maximum
      position at around 340 nm. The presence of one extra tyrosyl (Tyr-62) in PCa
      results in a weak increase of the maximal intensity in conjunction with a slight
      blue-shift of the maximum position.

PMID- 8268199
TI  - CD and FTIR studies of an immunogenic disulphide cyclized octadecapeptide, a
      fragment of a snake curaremimetic toxin.
AB  - In a previous paper, the systematic epitope screening of a snake curaremimetic
      toxin or toxin a was described by this group using a panel of synthetic
      octadecapeptides. The disulphide cyclized peptide (Cys-23,40)(23-40)
      corresponding to loop II of the native toxin was found to elicit, with no linkage
      to a carrier, neutralizing antisera against the toxin. We have now undertaken the
      conformational study of this immunogenic disulphide cyclized peptide by CD and
      FTIR. The CD study of the peptide was carried in aqueous solution under various
      conditions (pH, temperature, presence of micelles) and in trifluoroethanol
      solution. Low temperature, SDS micelles and trifluoroethanol were found to induce
      a beta-sheet formation (16 to 39%). FTIR spectra of the peptide in the solid
      state (dry film) and in D2O solution or deuterated-TFE solution (hydrated film)
      displayed some characteristic bands indicating the presence of beta-sheet (1623
      cm-1) and beta-turn (1637 cm-1; 1694 cm-1). These studies indicate that the
      immunogenic disulphide cyclized peptide (23-40) can adopt in solution an ordered
      structure.

PMID- 8268200
TI  - Presence of proteins recognized by mammalian cytochrome P-450 antibodies in
      Euglena gracilis.
AB  - We have attempted to probe three microsomal cytochrome P-450 isozymes in Euglena
      gracilis using immunochemical methods. They cross-react with anti-rat cytochrome
      P4502C11, cytochrome P4502E, and cytochrome P4502B. Activities of
      alkoxyphenoxazone dealkylation have been tested in living cells. In untreated
      cultures, the amount of proteins recognized by anti-cytochrome P4502C11 or anti
      cytochrome P4502E is high. Phenobarbital treatment increased the levels of
      microsomal proteins recognized by antibody to cytochrome P4502B, as well as
      dealkylases of pentoxyresorufin, but decreased the level of proteins recognized
      by anti-cytochrome P450C11 or cytochrome P4502E. These results suggest that these
      unicellular algae may contain different isozymes of microsomal cytochromes P-450,
      comparable to those in mammalian liver. They are cytochrome P-450 equivalents of
      mammalian isoenzymes 2C, 2E and 2B. However, we could not demonstrate ethanol
      induction of cytochrome P-450 equivalent to isoenzyme 2E. Its role in xeno- or
      endobiotic metabolism remains to be elucidated.

PMID- 8268201
TI  - Characterization of the three 125I-iodination isomers of human insulin-like
      growth factor I (IGF1).
AB  - Human insulin-like growth factor I (IGF1) was labeled with 125I and the resulting
      mixture of iodination isomers was separated by reverse-phase HPLC. Three major
      radioactive peaks were isolated and identified by sequencing as the expected
      three monoiodinated species. The ranking of the affinities of the three isomers
      for the human IGF1 receptor was found to be Tyr24(125I) > Tyr31(125I) >>
      Tyr60(125I). The Tyr31(125I) isomer was shown to have an affinity similar to that
      of unlabeled IGF1 and is thus the tracer of choice for IGF1. The tracers were
      stable upon storage at -20 degrees C for at least 3 months.

PMID- 8268202
TI  - Partial characterization of protein kinase C from an insect cell line.
AB  - The characteristics of protein kinase C (EC 2.7.1.37) from an insect cell line
      (Choristoneura fumiferana) have been described. DEAE-cellulose chromatography
      produced a major peak of activity which eluted at 0.04-0.055 M NaCl. The enzyme
      was sensitive to phosphatidylserine in the presence of calcium. Phorbol 12
      myristate 13-acetate (PMA) in nanomolar concentrations stimulated protein kinase
      C activity 8-fold over basal levels and reduced the enzymes requirement for Ca2+.
      The enzyme had a Ka of 10 nM for PMA. Diacylglycerols tested included diolein,
      dilinolein, diarachidonin, oleoyl-acetyl-glycerol, dioctonoyl-sn-glycerol,
      dipalmitin and distearin. A 2.5- to 3-fold activation was obtained in the
      presence of 26 microM diolein, 40 microM oleoyl-acetyl-glycerol and 46 microM
      dioctonoyl-sn-glycerol. The enzyme activity was sensitive to the inhibitor H-7
      and 50% inhibition was achieved at a concentration of 52 microM H-7.
      Phosphatidylinositol enhanced enzyme activity in the absence of
      phosphatidylserine but phosphatidylethanolamine had no effect.

PMID- 8268203
TI  - Purification and properties of cytochrome P-450 (P-450lun) catalyzing steroid 11
      beta-hydroxylation in Curvularia lunata.
AB  - Addition of 11-deoxycortisol to the culture medium of Curvularia lunata induced
      the increase of cytochrome P-450 content and steroid 11 beta-hydroxylase
      activity. The enzyme in cell-free extract produces cortisol from 11-deoxycortisol
      in the presence of NADPH and O2. The enzyme was partially stabilized by glycerol,
      11-deoxycortisol, GSH and PMSF. The hydroxylation activity was strongly inhibited
      by carbon monooxide and sulfhydryl reagents. Cytochrome P-450 located on the
      microsomal fraction was solubilized with Triton X-100 and sodium cholate and
      purified to apparent homogeneity by column chromatography. The purified
      cytochrome P-450 (P-450lun) has a molecular mass of 60 kDa and exhibits the
      absorption maximum at 392 nm in the spectrum of oxidized form in the presence of
      11-deoxycortisol. The reduced CO difference spectrum has a maximal peak at 448
      nm. 11 beta-Hydroxylation of 11-deoxycortisol was reconstituted by cytochrome P
      450lun, C. lunata NADPH-cytochrome P-450 reductase and DLPC in the presence of
      NADPH and O2 with a turnover number of 207 nmol/min per nmol of cytochrome P-450.
      The reductase and DLPC could be partially replaced with the enzyme purified from
      yeast or pig testis microsome and lipids purified from C. lunata, respectively. P
      450lun catalyzes bifunctionally 11 beta- and 14 alpha-hydroxylations of 11
      deoxycortisol. Deoxycorticosterone, progesterone, androstenedione and
      testosterone are hydroxylated in the similar manner.

PMID- 8268204
TI  - Identification of the characteristic amino-acid sequence for human alpha-amylase
      encoded by the AMY2B gene.
AB  - Human salivary and pancreatic alpha-amylases (HSA and HPA) are the respective
      gene products of the AMY1 and AMY2A genes. AMY2B is a newly found human alpha
      amylase gene. The presence of the AMY2B gene product (HXA) in the urine of
      healthy humans was examined. A mixture of alpha-amylases that seemed to contain
      HXA, judging from the substrate specificity, was purified from urine of healthy
      volunteers by affinity adsorption on starch and then by ion-exchange
      chromatography. The mixture was reduced and S-alkylated, and the product was
      digested with trypsin. The digest was separated by reversed-phase HPLC.
      LVGLLDLALEKDYVR and LVGLLDLALEK, which were found in the digest, are peptides of
      HXA, but not of HSA and HPA. The detection of these characteristic peptides of
      HXA demonstrates the presence of HXA in the urine of healthy humans.

PMID- 8268205
TI  - Purification and characterization of the myofibrillar form of myosin light-chain
      phosphatase from turkey gizzard smooth muscle.
AB  - The myofibrillar form of smooth-muscle myosin light-chain phosphatase (MLCP) was
      isolated from turkey gizzards. The enzyme was extracted from washed myofibrils
      and purified by affinity chromatography on a column of thiophosphorylated myosin
      20 kDa light-chain (LC20). The purified enzyme was a monomeric protein of 35 kDa
      and bound to unphosphorylated myosin with a binding constant of 5.45 x 10(4) M-1.
      It dephosphorylated both isolated phosphorylated light-chain (PLC20) and intact
      myosin as well as myosin light-chain kinase. The enzyme activity was stimulated
      by Mn2+, Mg2+, Ca2+, and inhibited by Co2+ ions. Okadaic acid inhibited the
      phosphatase activity with an IC50 (concentration required for 50% inhibition)
      value of 250 nM, that is around 25-times higher than required for type 1 protein
      phosphatase; however, the heat stable inhibitor-2 had no effect. The unique
      properties of the myofibrillar phosphatase as compared to smooth-muscle
      phosphatases so far described, suggest that the myofibrillar MLCP is a novel
      protein of this class. It has been also suggested that in vivo the myofibrillar
      MLCP exists in a complex with myosin light-chain kinase (MLCK) and a 63 kDa
      protein.

PMID- 8268206
TI  - Purification of the antibacterial fragments of guinea-pig major basic protein.
AB  - In this study, we tried to purify the antibacterial fragments of guinea-pig major
      basic protein (MBP) using Staphylococcus aureus. The antibacterial activity of
      MBP was not affected by the pyridylethylation, suggesting that the disulfide
      bonds were not necessary for the antibacterial activity. When pyridylethylated
      MBP was digested with alpha-chymotrypsin, the four potent antibacterial fragments
      (fragment V (Arg105-Tyr119), fragment IX (Thr1-Phe67), fragment X (Ile54-Leu97)
      and fragment XIII (Arg25-Phe67)) were isolated by reverse-phase high-performance
      liquid chromatography. Anti-MBP monoclonal antibody, BMK-13 neutralized the
      antibacterial activity of PE-MBP and fragments IX, X and XIII, but not the
      activity of fragment V, suggesting that Ile54-Phe67, the common amino-acid
      sequence of fragments IX, X and XIII, might be involved in the antibacterial
      activity of MBP. In fact, the synthetic peptide, Ile54-Phe67 exerted the
      antibacterial activity, and the activity was neutralized with BMK-13. The
      antibacterial activity of Ile54-Phe67 was lost by the modification with
      peptidylarginine deiminase which converted arginine residue to citrulline
      residue, suggesting that the arginine residues may be important for the
      antibacterial activity.

PMID- 8268207
TI  - Estimation of stabilities of staphylococcal nuclease mutants (Met32-->Ala and
      Met32-->Leu) using molecular dynamics/free energy perturbation.
AB  - We performed molecular dynamics (MD)/free energy perturbation (FEP) calculations
      to reproduce the experimental free energy difference of denaturation for
      staphylococcal nuclease mutant Met32-->Ala (M32A) and to predict the stability of
      the mutant Met32-->Leu (M32L). The calculated free energy difference of
      denaturation for the M32A of -1.9 kcal/mol was in good agreement with the
      experimental value. In the M32A, a small hydrophobic core formed by three
      aromatic rings (Tyr-27, Phe-34, Phe-76) in a wild-type crumbled as a result of
      exposure to water. The van der Waals interactions in the native state of the M32A
      were weaker than those of the wild-type, which strongly suggests that the Met-32
      is important for the stability of the enzyme. The M32L has not been available
      yet, but is expected to retain the small hydrophobic core. The free energy
      difference of denaturation for the M32L was calculated to be 1.6 kcal/mol. The
      MD/FEP simulation showed that the native state structure of the M32L was only
      slightly changed when compared with that of the wild-type. It was suggested that
      the M32L is more stable than the wild-type because the electrostatic interactions
      in the denatured state are more disadvantageous than those in the native state.

PMID- 8268208
TI  - Xenobiotic induction of quinone oxidoreductase activity in lens epithelial cells.
AB  - Xenobiotic regulatory elements have been identified for enzymes which ameliorate
      oxidative damage in cells. Zeta (zeta)-crystallin, a taxon-specific
      enzyme/crystallin shown to be a novel NADPH-dependent quinone reductase, is found
      in a number of tissues and cell types. This study shows that zeta-crystallin is
      present in mouse lens epithelium, as well as in the alpha TN4 mouse lens
      epithelial cell line. To determine whether zeta-crystallin is an inducible
      quinone reductase, cell cultures were exposed to the xenobiotics, 1,2
      naphthoquinone and beta-naphthoflavone. Assays of cellular homogenates showed
      that quinone reductase activity was stimulated greater than 70% and 90%,
      respectively, over the control cells. This observed activity was sensitive to
      dicumarol, a potent inhibitor of quinone reductase activity. 1,2-Naphthoquinone-
      and beta-naphthoflavone-exposed cells were found to exhibit 1.47- and 1.68-fold
      increases, respectively, in zeta-crystallin protein concentration. A comparable
      increase in zeta-crystallin mRNA was indicative of an induction in zeta
      crystallin expression in response to naphthalene challenge. Lens epithelial cells
      were also checked for DT-diaphorase, a well-known cellular protective enzyme
      which can catalyze the two-electron reduction of quinones. Slot blot analyses
      indicated that alpha TN4 cells exposed to 1,2-naphthoquinone and beta
      naphthoflavone exhibited 2.71- and 6.81-fold increases in DT-diaphorase
      concentration when compared to the control cells. The data suggest that while DT
      diaphorase is most likely responsible for the majority of the observed increase
      in quinone reductase activity, the zeta-crystallin gene also undergoes activation
      which is apparently mediated by a xenobiotic-responsive element.

PMID- 8268209
TI  - Aldose and aldehyde reductases from human kidney cortex and medulla.
AB  - Aldose reductase and aldehyde reductase were purified to homogeneity from
      multiple samples of human kidney cortex and medulla. A single form of aldose
      reductase is expressed in kidney that is kinetically and immunochemically
      indistinguishable from aldose reductase expressed in other human tissues. The
      results support the conclusion that there is a single human aldose reductase, and
      that aldose reductase is expressed in a reduced form, characterized by high
      sensitivity to aldose reductase inhibitors and ability to catalyze the reduction
      of glucose. Aldose reductase is easily oxidized to a form that is insensitive to
      aldose reductase inhibitors and unable to catalyze the reduction of glucose. This
      form does not appear to exist in vivo, even in kidney from diabetics. There is
      wide variation in the level of expression of aldose reductase in kidney,
      especially in cortex. The immunochemically separate but similar aldehyde
      reductase is also expressed in kidney as a single enzyme indistinguishable from
      aldehyde reductase from other human tissues. Aldehyde reductase levels exceed
      those of aldose reductase, both in cortex and medulla.

PMID- 8268210
TI  - Dynamics and thermodynamics of acid-alkaline transitions in metmyoglobins lacking
      the usual distal histidine residue.
AB  - The kinetics of the acid-alkaline transition in the ferric myoglobins from the
      gastropodic mollusc Dolabella auricularia and the shark Mustelus japonicus, which
      possess the distal Val E7 and Gln E7, respectively, has been investigated using
      the paramagnetic 1H-NMR saturation transfer measurements in order to gain insight
      into functional properties of these non-His distal residues. Both myoglobins
      possess the penta-coordinated heme below the pK of the transition (7.8 and 10.0
      for Dolabella and Mustelus myoglobins, respectively) and bind OH- above the pK.
      The pH dependence of the transition rates and the relatively high activation
      barrier (58 +/- 9 kJ/mol) for the dissociation of the Fe-bound OH- in Dolabella
      myoglobin indicate a strong interaction between the bound ligand and the
      guanidino NH proton of the Arg E10 in Dolabella myoglobin. Such a strong
      interaction between Fe-bound OH- and the Arg E10 side-chain in Dolabella
      myoglobin is also manifested in the EPR spectra. For Mustelus myoglobin, the pH
      and temperature dependence studies on the kinetics strongly suggest that the
      distal Gln E7 in this myoglobin does not contribute significantly to stabilize
      the Fe-bound ligand.

PMID- 8268211
TI  - Evidence for proximal cysteine and lysine residues present at the nucleotide
      domain of rabbit muscle creatine kinase.
AB  - Inactivation of rabbit muscle creatine kinase by o-phthalaldehyde was
      investigated. The loss of enzyme activity was concomitant with the increase in
      fluorescence intensity at 410 nm. The modified enzyme showed a characteristic
      absorption peak at 336 nm. These evidences suggested that the mechanisms of
      inhibition of creatine kinase by o-phthalaldehyde involves binding of the thiol
      and the epsilon-amino group of enzyme leading to the formation of isoindole
      derivative. None of the substrates, except Mg-ATP, provided protection against o
      phthalaldehyde inhibition. This was corroborated by fluorescence studies. Double
      inhibition experiments showed that p-chloromercuricphenyl sulphonic acid, a thiol
      specific reagent, binds to the same cysteine which is also involved in the o
      phthalaldehyde reaction. Stoichiometric results indicated that 2 mol of o
      phthalaldehyde were incorporated per mole of enzyme molecule upon complete
      inactivation. Denaturation of creatine kinase by urea or heat treatment prior to
      o-phthalaldehyde addition resulted in the decrease of fluorescence intensity
      indicating that native conformation of the enzyme is essential for isoindole
      derivative formation.

PMID- 8268212
TI  - Casein kinase II beta-subunit inhibits the activity of the catalytic alpha
      subunit in the absence of salt.
AB  - Casein kinase II (CKII) has a subunit structure of alpha 2 beta 2 where alpha is
      the catalytic subunit. Recombinant Drosophila casein kinase II alpha-subunit
      expressed in insect cells is inhibited by NaCl, thermally labile and inactivated
      by binding to plastic. In the presence of detergent (Tween 80) recombinant alpha
      subunit has a kcat of 249 min-1 (Km 170 microM) for the peptide substrate
      RRRDDDSDDD-NH2, compared to recombinant Drosophila CKII with a kcat of 71 min-1
      (per mol alpha) (Km 42 microM) and bovine CKII with a kcat of 123 min-1 (per mol
      alpha) (Km 45 microM) when measured in the absence of NaCl. The kcat values of
      bovine CKII and recombinant Drosophila CKII measured in the presence of 150 mM
      NaCl were 429 min-1 (per mol alpha) (Km 82 microM) and 204 min-1 (per mol alpha)
      (Km 51 microM), respectively. Since the kcat for the Drosophila alpha-subunit is
      approx. 3-fold greater than the Drosophila CKII measured in the absence of added
      salt these results indicate that the beta-subunit acts primarily as an inhibitory
      subunit.

PMID- 8268213
TI  - Spectroscopic study of the temperature-dependent conformation of glucoamylase.
AB  - Vibrational circular dichroism, electronic circular dichroism and infrared
      absorption with Fourier self-deconvolution have been used for a conformational
      study of the small form, G2, of glucoamylase, 1,4-alpha-D-glucan glucohydrolase
      from Aspergillus niger (EC 3.2.1.3) in aqueous solution. From the temperature
      dependence of spectra measured from 25 degrees C to 60 degrees C it was seen that
      the helical content is relatively constant to 50 degrees C and then sharply
      decreases by a factor of more than three by 60 degrees C. This decrease in helix
      is primarily compensated by a rise in the fraction of beta-sheet; but bend, turn
      and 'other' components also increase. By comparison of the three techniques, it
      was determined that the electronic CD analysis was quantitatively in error due to
      interference by glycosidic residues. The inherent resolution of the vibrational
      techniques, FTIR and VCD, avoids such interference.

PMID- 8268214
TI  - Charge isomers of urinary bikunin (trypsin inhibitor).
AB  - It was observed that the purified urinary bikunin (trypsin inhibitor) consisted
      of four major isomers with different electric charges which could be separated by
      HPLC using a Mono Q column. These isomers revealed the same antitrypsin activity
      and did not show any differences in the apparent molecular weight by SDS-PAGE,
      amino-acid composition, N-terminal amino-acid sequence (1-40) and C-terminal
      amino acid (Leu). The contents of sialic acid and uronic acid were also identical
      among these isomers. However, analysis of chondroitin sulfate revealed all the
      glycosaminoglycan chains of these isomers were undersulfated, comprising
      nonsulfated and 4-sulfated disaccharide units, and 4-sulfated disaccharide unit
      ratio varied among these isomers. After the chondroitin ABC lyase digestion, all
      the isomers were eluted at the same position on a Mono Q column chromatography.
      These results indicated that charge isomers of urinary bikunin was attributed to
      the difference on sulfation ratio in a glycosaminoglycan chain.

PMID- 8268215
TI  - Structural analysis of the extension peptides on matrix forms of type V collagen
      in fetal calf bone and skin.
AB  - The structure of the extension peptides retained on the tissue form of type V
      collagen molecules was determined. Type V collagen alpha chains containing
      extension peptides were extracted from fetal calf skin and bone by 4 M guanidine
      HCl and 0.5 M acetic acid, respectively. Collagens present in both extracts were
      fractionated by sodium chloride precipitation. The collagen alpha(V) chains were
      then resolved by reverse-phase high performance liquid chromatography. The N
      terminal extension peptides were characterized by direct sequence analysis after
      deblocking with pyroglutamate amino-peptidase and analysis of the products of
      digestion by bacterial collagenase, chymotrypsin, V8 protease and endoproteinase
      Lys-C. The results showed that the retained extension peptides on type V collagen
      molecules in the extracellular matrix of skin and bone were amino-propeptides and
      that the alpha 2(V) chain retains an intact amino-propeptide while the alpha 1(V)
      chain appears to be partially processed. The extended alpha 1(V) chain isolated
      from fetal calf bone gave an identical amino-terminal sequence to that of the
      alpha 1(V) chain isolated from fetal calf skin, suggesting that a specific enzyme
      may be involved in processing the alpha 1(V) amino-propeptide.

PMID- 8268216
TI  - Zinc as modulator of oxygenation function and stabilizer of quaternary structure
      in earthworm hemoglobin.
AB  - Blood of the earthworm Pheretima hilgendorfi contains 10.7 mM Ca, 2.0 mM Mg, 75.5
      mM Na, 5.9 mM K, 0.9 mM Zn and 0.3 mM Mn. Some of these cations cannot be removed
      completely from the blood by dialysis, and 36 atoms of Ca, 1-3 atoms of Mg and 1
      2 atoms of Zn per 164 atoms of Fe were retained in purified preparation of the
      hemoglobin (Hb). At physiological pH, oxygen affinity and the Hill coefficient at
      half saturation (n1/2 value) of the Hb increased in the presence of 100 mM of Ca,
      Mg or Na. These effects were in the order of Ca > Mg > Na. At physiological
      concentration, however, the effect of each of these three cations on oxygenation
      was rather small. On the other hand, Zn gave a remarkable effect at less than 1
      mM. This suggests a possibility that Zn acts as a primal modulator for the
      oxygenation function of the Hb in vivo. Oxygenation data at various pH values in
      the presence of each cation strongly suggest that Zn binds to a site different
      from those for the other three cations. Zn at a concentration of only 1 mM
      protected considerably the dissociation of the whole molecule to smaller
      components at alkaline pH and Zn thus contributes to the stabilization of the
      quaternary structure of the Hb.

PMID- 8268218
TI  - Chemical synthesis and expression of a gene coding for human muscle
      acylphosphatase.
AB  - A DNA sequence coding for human muscle acylphosphatase has been constructed using
      16 chemically synthesized oligonucleotides. The 300-bases long DNA sequence has
      been cloned in the pT7.7 Escherichia coli expression vector and in the pYEpsec1
      Saccharomyces cerevisiae expression vector. In both cases a high level of
      expression of acylphosphatase has been observed. The recombinant proteins have
      been purified to homogeneity and assayed in comparison with the natural protein,
      using benzoylphosphate as a substrate and phosphate as a competitive inhibitor.
      The recombinant enzymes expressed in the two microorganisms maintain the kinetic
      properties of the natural protein. In addition, NMR analysis shows that the gross
      fold of the two recombinant enzymes is correct.

PMID- 8268217
TI  - Human dihydrolipoamide succinyltransferase: cDNA cloning and localization on
      chromosome 14q24.2-q24.3.
AB  - We isolated cDNA for dihydrolipoamide succinyltransferase from a human fibroblast
      cDNA library in lambda gt11. The cDNA revealed that the human dihydrolipoamide
      succinyltransferase lacked a sequence motif of an E3 and/or E1 binding site. This
      suggests that the human dihydrolipoamide succinyltransferase possesses a unique
      structure consisting of two domains in contrast with the dihydrolipoamide
      acyltransferases of other alpha-keto acid dehydrogenase complexes. In addition,
      we found that the human dihydrolipoamide succinyltransferase gene is located on
      chromosome 14 at q24.2-q24.3 and that a sequence related to the dihydrolipoamide
      succinyltransferase gene is located on chromosome 1 at p31. Interestingly, the
      gene for the dihydrolipoamide acyltransferase of the branched chain alpha-keto
      acid dehydrogenase complex is also located on chromosome 1p31 (Zneimer et al.
      (1991) Genomics 10, 740-747).

PMID- 8268220
TI  - Expression of serum amyloid A genes in mink during induction of inflammation and
      amyloidosis.
AB  - Serum amyloid A (SAA) is an acute phase protein and the precursor of amyloid
      protein A (AA) in deposits of secondary amyloidosis. Several isotypes exist in
      mink, but previous studies suggest that mink AA is derived from only one. To
      assess the effect of repeated episodes of inflammation and induction of
      amyloidosis, qualitative and quantitative changes in hepatic and extrahepatic SAA
      mRNA were studied. Young female mink received subcutaneous lipopolysaccharide
      injections for amyloid induction. Studies were performed using RNA probes and
      oligonucleotide probes specific for each of two SAA mRNA species. Northern blot
      hybridization showed that hepatic SAA1 and SAA2 mRNA levels increased
      dramatically after inflammatory stimulation, and were subsequently maintained at
      elevated levels, showing considerable interindividual variation, but only a
      slight decrease during repeated inflammatory stimuli and the early stages of
      amyloid deposition. No preferential accumulation of mRNA specifying a particular
      isotype was found during the experiment. Differential expression of mink SAA mRNA
      during repeated inflammatory stimulation does not seem to explain why only SAA2
      derived AA is found in amyloid deposits. Extrahepatic SAA mRNA seemed to be
      independently regulated and may thus represent another, yet not characterized,
      SAA isotype.

PMID- 8268219
TI  - Identification of the 5' regulatory elements of avian lipoprotein lipase gene:
      synergistic effect of multiple factors.
AB  - The organization of cis-acting regulatory elements of the chicken lipoprotein
      lipase gene was investigated in 5.4 kb of 5' flanking sequences. Various lengths
      of 5' flanking sequence were linked to the bacterial chloramphenicol
      acyltransferase (CAT) gene and transfected into primary cultures of chicken
      adipocytes by DEAE-dextran transfection method. Negative elements are present
      between -1947 and -139 of the 5' flanking sequence. Removal of these sequences
      revealed the presence of positive elements located within 138 bp upstream of the
      major transcription start site. Sequence analysis showed that the region from the
      major transcription start site to -138 contains an inverted GC box (ACCACGCCCC),
      a CCAAT element and two direct repeats of the octamer motif, ATTTGCAT. DNase I
      footprinting assays using a probe extending from -175 to +191, identified three
      sites protected by nuclear factors. Site I (-126 to -123), a C-rich sequence,
      GCCC, was identified only on the coding strand. Site II covered the sequence from
      -95 to -68 and includes the GC box. Site III, from -53 to -26, contained two
      octamer repeats. Site I is the 5' portion of a 10 bp sequence (CCCTCCCCCC; -126/
      116) which is perfectly conserved in the avian and the human promoter. Single or
      multiple copies of a 37 bp DNA fragment (-138/-102) containing the 10 bp
      conserved sequence were cloned into LPLCAT-51, upstream or downstream of the
      major transcription start site and in both orientations; transfection and CAT
      activity assays with these constructs indicate that the -138/-102 fragment has an
      enhancer like activity. Additional 5' and internal deletions of LPLCAT-138
      suggest that the factors binding to the C-rich element, the GC box and the two
      octamer repeats have a synergistic effect on promoter activity.

PMID- 8268221
TI  - Characterization of regulatory sequences and nuclear factors that function in
      cooperation with the promoter of the human thymidylate synthase gene.
AB  - To identify the essential sequence of the promoter of the human thymidylate
      synthase (hTS) gene, deletion mutants were constructed and assayed for promoter
      activity. The essential sequence was located within 65 bp upstream from the major
      cap site and a sequence that reduces the promoter activity was found in a region
      upstream from the essential promoter sequence. We previously identified two DNA
      binding nuclear factors, NF-TS2 and NF-TS3, that bind to a region around the site
      of initiation of translation of the hTS gene. In this study, we confirmed the
      binding site of these factors by gel mobility shift analysis and found that NF
      TS2 is the major factor that binds to the hTS gene in HeLa cells, whereas NF-TS3
      is the major factor in the TIG-1 line of human fibroblast cells. To clarify the
      function of these factors, we examined the effects of the binding of these
      factors on the promoter activity. Our findings suggest that the binding of NF-TS2
      enhances the promoter activity of the hTS gene in HeLa cells, whereas the binding
      of NF-TS3 represses the activity of the same promoter in TIG-1 cells.

PMID- 8268222
TI  - Over-expression of the yeast multifunctional arom protein.
AB  - The pentafunctional arom protein of Saccharomyces cerevisiae is encoded by the
      ARO1 gene. Substantial elevation of the levels of the arom protein (25-fold) was
      achieved in yeast using a vector that exploited the ubiquitin-fusion cleavage
      system of yeast. However, attempts to express the N-terminal 3-dehydroquinate
      synthase domain (E1) or the internal 3-dehydroquinase domain (E2) using the same
      system did not succeed. The yeast arom protein was successfully purified from the
      over-expressing transformant, and was found to possess all five enzymatic
      activities in a ratio similar to that observed in crude cell extracts. The
      purified material consisted mainly of a polypeptide that co-migrated in SDS-PAGE
      with intact arom proteins from other species.

PMID- 8268223
TI  - Co-expression of mutant and normal human insulin receptors in COS 7 cells.
AB  - In order to assess the interference of the mutant insulin proreceptor on normal
      receptor function and formation of proreceptor-receptor heterotrimers (alpha beta
      proreceptor), COS 7 cells were transfected with the same amount of expression
      plasmid (pGEM3SV) containing wild-type, a mutant proreceptor cDNA and both, using
      the DEAE-dextran method. Scatchard analysis of insulin binding data revealed that
      there was an approx. 50-fold higher receptor concentration in the transfected
      cells than in untransfected cells. After 0.025% trypsin treatment, insulin
      binding to the cells expressed with wild-type, proreceptor and both increased by
      1-fold, 2.9-fold and 1.5-fold of the untreated cells, respectively. In the
      presence of 167 nM insulin, the amounts of phosphate incorporated into the 95 kDa
      protein beta-subunits and 210 kDa proreceptors from co-transfected cells, were
      identical to those of an in vitro mixture of the wild-type and the mutant
      receptors. At 10 nM insulin, the proreceptors from co-transfected cells normally
      autophosphorylated by insulin stimulation, whereas those mixed in vitro did not
      (73.3 +/- 9.3 vs. 29.6 +/- 2.6% of the maximal effect, n = 4, P < 0.01). However,
      at a similar concentration of insulin, the phosphate incorporation into Glu
      80/Tyr-20 polymers by receptors from co-transfected cells was decreased when
      compared with a in vitro mixture (9.0 +/- 2.6 vs. 22.5 +/- 6.7% of the maximal
      effect at 4 nM, n = 6, P < 0.01), although the basal and maximally stimulated
      phosphate incorporation were comparable among these groups.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8268224
TI  - Expression and characterization of recombinant mouse mastocytoma histidine
      decarboxylase.
AB  - The possibility of post-translational processing of mouse mastocytoma histidine
      decarboxylase (HDC; EC 4.1.1.22) was investigated. The molecular mass of the
      recombinant HDC expressed in Sf9 cells using HDC cDNA from mouse mastocytoma
      cells was determined to be 74 kDa by SDS-PAGE. In contrast to the native HDC from
      mastocytoma cells, the recombinant 74 kDa HDC was essentially inactive and
      precipitable in Sf9 cells. On the other hand, deletion mutants of the recombinant
      HDC lacking a C-terminal region equivalent to 10 (64 kDa) or 20 kDa (54 kDa) in
      size were present as active forms in the soluble fraction of Sf9 cells. To
      examine the C-terminal deletion of the 74 kDa species yielding the 53 kDa species
      by means of the immunoblotting analysis, two peptides (corresponding to residues
      323-337 and 572-586 of the recombinant 74 kDa HDC peptide) were synthesized, and
      rabbit antiserum specific for each peptide was prepared. On immunoblotting
      analysis, anti-peptide 323-337 antiserum recognized both the recombinant 74 kDa
      and native enzyme subunit peptides, but anti-peptide 572-586 antiserum recognized
      only the recombinant 74 kDa peptide, i.e., not the native enzyme subunit peptide.
      Furthermore, HDC activity in the crude extract from Sf9 cells was not
      precipitable with antipeptide 572-585 antiserum. These results strongly suggest
      that the 53 kDa subunit peptide of native mastocytoma HDC is derived from the
      unidentified inactive 74 kDa HDC peptide, probably by post-translational
      processing of HDC in its C-terminal region.

PMID- 8268225
TI  - Induction of chicken avidin and related mRNAs after bacterial infection.
AB  - Inflammation-mediated avidin gene expression in the chicken was studied using
      hybridization analysis, polymerase chain reaction (RT-PCR) and sequencing. The
      results indicate the presence of avidin mRNA in the oviduct and intestine after
      Escherichia coli infection. The mRNA for the inflammation-induced avidin was
      mainly encoded by the avidin gene, but the avidin-related genes, avr2 and avr3,
      were also transcribed at a low level in the oviduct and intestine, respectively.
      Because avidin is also induced in the chicken oviduct by progesterone, our
      results indicate a multifactorial regulation of avidin gene expression.

PMID- 8268226
TI  - The structure of the human thyroxine binding globulin (TBG) gene.
AB  - A portion of the human X-chromosome (> 5 kb) encoding the translated portion of
      the thyroxine-binding globulin (TBG) gene was sequenced. The primary templates
      for sequencing were isolated from a human X-chromosome library (two positive
      plaques from 400,000 screened initially with a TBG cDNA probe) or were produced
      by PCR amplification using leucocyte genomic DNA as the amplification template.
      Potential hormone response elements (HREs) were identified at either end of the
      gene. These HREs have sequences based on the consensus half-site of thyroid
      hormone response elements, although it is unclear whether the structures are
      functional HREs. Other potential regulatory elements also were identified towards
      the 3' end of the gene.

PMID- 8268227
TI  - Polyamines modulate streptomycin-induced mistranslation in Escherichia coli.
AB  - The effects of intracellular levels of polyamines on both the in vivo inhibition
      of protein synthesis and the decrease of translation accuracy induced by
      streptomycin have been studied in polyamine-auxotrophic strains of Escherichia
      coli infected with the MS2 bacteriophage. The amount of viral coat protein formed
      was strongly reduced upon addition of increasing concentrations of streptomycin
      to polyamine-supplemented bacteria. In contrast, the antibiotic almost did not
      inhibit coat protein synthesis in polyamine-starved cells. The increase of
      mistranslation frequency elicited by streptomycin was only observed in bacteria
      grown with putrescine. In these cells several coat protein-satellites were
      detected after two-dimensional gel electrophoresis. These proteins, more basic
      than the normal MS2 coat protein, contain multiple substitutions of lysine for
      asparagine.

PMID- 8268228
TI  - Tissue specific and developmental expression of rat long-and medium-chain acyl
      CoA dehydrogenases.
AB  - Utilization of fatty acids for energy varies among mammalian tissues and during
      development due to changes in expression of enzymes of mitochondrial beta
      oxidation. To discern whether two related nuclear genes are expressed similarly,
      the tissue distribution and developmental profile of the rat long- and medium
      chain acyl-CoA dehydrogenase (LCAD and MCAD) mRNAs were compared. A 1451 base
      full-length LCAD cDNA from neonatal rat aorta was used to study mRNA accumulation
      in adult and fetal rat tissues. LCAD and MCAD mRNAs were expressed in aorta,
      heart, and brown fat at levels 8-40 fold greater than in liver, kidney, and
      duodenum. Brain, placenta, ovary, testes, and skeletal muscle showed the least
      mRNA. Western blots of adult tissues with anti-rat LCAD antiserum showed
      corresponding amounts of LCAD protein subunits. LCAD mRNA was detectable in
      heart, liver, kidney, and brain of fetal rats and increased with age. LCAD and
      MCAD mRNAs were present in brown fat in 2-10 fold greater amounts compared to
      other tissues from the newborn period to the end of the weaning period. The high
      level of expression of LCAD and MCAD mRNA in aorta, heart, and brown fat likely
      reflects the high energy requirements of those tissues. Differential expression
      of LCAD and MCAD mRNAs reflects not only inherent gene prescribed programs, but
      also external influences such as hormones and diet.

PMID- 8268229
TI  - Genomic sequence of mouse COL1A1 encoding the collagen propeptides.
AB  - The nucleotide sequences of the mouse pro alpha 1(I) gene regions coding for the
      N- and C-propeptides is reported. The exon-intron structure was highly homologous
      to human COL1A1 and the deduced amino acid sequences of the N- and C-propeptides
      showed 67% and 91% identity with the human sequence. This gene sequence
      information will allow the production of specific gene mutations by site-directed
      mutagenesis to study the structure and function of these important propeptide
      domains.

PMID- 8268230
TI  - Human ribosomal protein L4: cloning and sequencing of the cDNA and primary
      structure of the protein.
AB  - The cloning and sequencing of a cDNA for human ribosomal protein L4 is reported.
      The corresponding mRNA has a very short 5' untranslated region initiating with a
      sequence of 12 pyrimidines, characteristic of all vertebrate ribosomal protein
      mRNAs. The deduced amino acid sequence shows that human ribosomal protein L4 has
      425 amino acid residues and a calculated molecular mass of 47,821 Da. Comparison
      with the homologous counterparts of Xenopus, Drosophila and yeast shows that this
      protein has a very conserved amino-terminus region and an extremely divergent
      carboxyl-terminus portion.

PMID- 8268232
TI  - Cloning and sequence analysis of cDNA encoding the bovine testis-derived male
      enhanced antigen (Mea).
AB  - A full-length cDNA encoding the bovine male enhanced antigen (Mea) has been
      cloned from a bovine testicular cDNA library and sequenced. The primary structure
      of the bovine Mea peptide deduced from this nucleotide sequence has 174 amino
      acid residues and is highly homologous to human (95.9%, 165/172) and mouse
      (92.5%, 161/174) Mea gene products. It is located on an autosome, and is
      expressed highly in the testes.

PMID- 8268231
TI  - Cloning and sequencing of porcine moesin and radixin cDNA and identification of
      highly conserved domains.
AB  - The full length cDNA of porcine moesin and radixin have been cloned and
      sequenced. Comparison of the closely related sequences of human, murine and
      porcine moesin, ezrin and radixin with a protein from Echinococcus
      multilocularis, an evolutionarily quite distant human parasite, reveals several
      highly invariant domains in the aminoterminal and carboxyterminal regions. Most
      of these conserved domains are clustered around tyrosine residues that are
      putative phosphorylation sites for tyrosine phosphokinases.

PMID- 8268233
TI  - Nucleotide sequence of the gene coding for Clostridium botulinum (Clostridium
      argentinense) type G neurotoxin: genealogical comparison with other clostridial
      neurotoxins.
AB  - The neurotoxin gene from Clostridium botulinum type G was cloned as a series of
      overlapping DNA fragments generated using polymerase chain reaction (PCR)
      technology and primers designed to conserved regions of published botulinal toxin
      (BoNT) sequences. The 5'-end of the gene was obtained using a primer based on a
      conserved region of the nontoxic-nonhaemagglutinin gene lying upstream of the
      toxin gene. Translation of the nucleotide sequence derived from the cloned PCR
      fragments demonstrated that the gene encodes a protein of 1297 amino acid
      residues (rmm 149, 147). Comparative alignment of the determined BoNT/G sequence
      with those of other clostridial neurotoxins revealed highest sequence relatedness
      (approx. 58% amino acid identity) with BoNT/B of proteolytic and non-proteolytic
      C. botulinum. Tetanus toxin (TeTx) and other BoNT types revealed lower levels of
      relatedness with BoNT/G (approximate range 35-42% amino acid identity).

PMID- 8268234
TI  - Molecular cloning and sequencing of rat Max cDNA: castration-induced expression
      of the 2 kb transcript in male accessory sex organs of rats.

PMID- 8268235
TI  - An archaeal trkA homolog near dnaK and dnaJ.
AB  - The first trkA gene homolog in the phylogenetic domain Archaea is reported. The
      gene is located near the dnaK-dnaJ gene cluster in the genome of Methanosarcina
      mazei S-6, and encodes a protein homologous to the only other TrkA known, i.e.,
      that of the bacterium Escherichia coli, involved in K+ transport. This finding
      supports an essential, evolutionarily early, and conserved role for this gene in
      cell survival and adaptation.

PMID- 8268236
TI  - Molecular cloning and analysis of the expression of the E1 beta subunit of
      branched chain alpha-ketoacid dehydrogenase in mice.
AB  - The cDNA sequence encoding the murine liver E1 beta subunit of the branched-chain
      alpha-ketoacid dehydrogenase complex (BCKAD) was determined. In the region
      encoding the mature E1 beta subunit protein, both the nucleotide composition and
      predicted amino acid sequence are highly conserved between murine, rat, human,
      and bovine species. In contrast, they are less well conserved in the 5' sequence
      encoding the amino terminal preprotein sequence and 3' untranslated region. The
      pattern of tissue-specific expression of three BCKAD subunit RNAs was determined
      to be similar in both rat and murine tissues except for that observed in murine
      liver, where a higher than expected level of E1 beta subunit RNA was observed.
      Variation in the levels of this subunit might play a major role in the regulation
      of the overall ability of the murine liver to modulate BCKAD content in response
      to changing physiologic needs.

PMID- 8268237
TI  - A heritable point mutation in an extracellular domain of the TSH receptor
      involved in the interaction with Graves' immunoglobulins.
AB  - The TSH receptor (TSHR) is the central antigen in Graves' disease. Variant
      receptor proteins, arising from mutations in the TSHR gene, may play a role in
      the pathogenesis of the disease. Therefore, we analysed the TSHR from a 38-year
      old patient affected with autoimmune hyperthyroidism, diffuse goitre and
      ophthalmopathy. Reverse transcription PCR and DNA amplification followed by DNA
      sequencing revealed a point mutation (C-->A) at cDNA position 253 in one of two
      alleles. This leads to the replacement of a proline (CCC) by threonine (ACC) at
      amino acid position 52 of the predicted receptor protein. Secondary structure
      predictions indicated a major change of protein structure as a result of the
      mutation. By using allele-specific PCR, we were able to show that this mutation
      is heritable. Screening of 50 random individuals revealed that four of them also
      carried this mutation in the heterozygous state. This study shows the presence of
      different forms of the TSHR gene in the population. The mutation, which is in a
      portion of the receptor apparently involved in binding of Graves'
      immunoglobulins, is discussed as to its possible pathophysiological role in
      autoimmune hyperthyroidism.

PMID- 8268238
TI  - Deletion of C-terminal 113 amino acids impairs processing and internalization of
      human insulin receptor: comparison of receptors expressed in CHO and NIH-3T3
      cells.
AB  - We have studied the structure and the function of a truncated human insulin
      receptor in which 113 amino acids (aa 1231-1343) at the C-terminus of the beta
      subunit were deleted. In this study, wild-type and truncated insulin receptors
      were expressed by stable transfection in NIH-3T3 cells and CHO cells. The
      mutation impairs post-translational processing of the insulin receptor;
      proteolytic cleavage is retarded, and degradation of the truncated receptor is
      accelerated. Furthermore, insulin-stimulated autophosphorylation of the mutant
      insulin receptor is impaired. This is associated with a defect in insulin
      stimulated endocytosis. Finally, in NIH-3T3 cells, the mutant insulin receptor
      failed to mediate the mitogenic effects of insulin. In CHO cells, transfection of
      insulin receptor cDNA (either wild-type or mutant) did not alter mitogenic
      response to insulin. It has previously been shown that deletion of 43 amino acids
      at the C-terminus of the beta-subunit did not affect insulin receptor tyrosine
      kinase activity. Our data suggest that the structural domain located 43-113 amino
      acids from the C-terminus appears to have several functional roles. First, the
      domain appears to promote folding of receptor into the optimal conformation for
      post-translational processing. Second, the presence of this domain appears to
      promote the stability of the receptor beta-subunit in intact cells. Finally,
      perhaps as a consequence of the effects upon the stability of the receptor, this
      domain is required in intact cells for insulin-stimulated autophosphorylation and
      signal transmission.

PMID- 8268239
TI  - Topology of catalase assembly in human skin fibroblasts.
AB  - The biogenesis, assembly and import of the peroxisomal enzyme catalase was
      studied in human skin fibroblasts from control persons and from patients with the
      Zellweger syndrome. For this purpose, two monoclonal antibodies were generated
      which are able to discriminate between the monomeric or dimeric form and the
      tetrameric, enzymically active conformation of the enzyme. Metabolic labelling
      studies showed that catalase is assembled to the tetrameric conformation within
      one hour after its synthesis, while it is still in the cytosol of the cell.
      Subsequently, the enzyme becomes particle-bound in the control cells, a process
      that is retarded by addition of the catalase inhibitor 3-amino-1,2,4-triazole.
      However, the tetramer remains in the cytosol in cells from Zellweger patients. It
      is concluded that newly synthesized catalase can be assembled to a tetramer in
      the cytosol in human skin fibroblasts. Unfolding of this tetramer prior to import
      into peroxisomes is indicated.

PMID- 8268240
TI  - Nucleoside-triphosphate binding of the two cytosolic components of the
      respiratory burst oxidase system: evidence for its inhibition by the 2',3'
      dialdehyde derivative of NADPH and desensitization in their translocated states.
AB  - Affinity labeling of the two cytosolic components of the respiratory burst
      oxidase system, p49-phox and p63-phox, from resting porcine neutrophils was
      carried out with [32P]NADPH dialdehyde (oNADPH), [32P]oGTP and [32P]oATP. p49
      phox and p63-phox showed 10-times higher affinities for both oGTP and oATP than
      for oNADPH, suggesting that they are nucleoside triphosphate (NTP)-binding
      proteins, rather than the NADPH-binding site of the oxidase. In addition, oNADPH
      markedly inhibited the affinity labeling of p49-phox with [32P]oGTP and
      [32P]oATP, well reflecting its inhibitory effect on the oxidase activity in the
      cell-free system, which was previously reported to propose the NADPH-binding site
      in a cytosolic component. Stimulation of porcine neutrophils with either myristic
      acid or phorbol myristate acetate resulted in great enhancement of the oxidase
      activity, and in considerable translocation of p49-phox and p63-phox.
      Nevertheless, the affinity labeling of the stimulated cell membranes in both
      cases revealed no labeled bands corresponding to molecular masses of 49 kDa and
      63 kDa. p49-phox derived from the stimulated membranes had lost its [32P]oGTP
      binding ability in contrast with that from resting cytosol, suggesting that the
      NTP-binding sites of the two cytosolic components may be desensitized on NTP
      binding in their translocated states.

PMID- 8268241
TI  - cAMP-induced changes of intracellular free Mg2+ levels in human erythrocytes.
AB  - To examine the role of cAMP in the regulation of intracellular free magnesium
      concentration ([Mg2+]i), we measured [Mg2+]i in human erythrocytes by 31P-NMR
      spectroscopy. (-)-Isoproterenol, forskolin, Bt2cAMP and 8-bromo-cAMP decreased
      [Mg2+]i in human erythrocytes. Bt2cAMP did not increase the efflux rate of Mg2+
      from erythrocytes. HA1004, a potent inhibitor of cAMP-dependent kinases, markedly
      increased the [Mg2+]i in a Mg(2+)-free buffer solution. Addition of 8-bromo-cGMP
      or 12-O-tetradecanoylphorbol 13-acetate (TPA) did not affect the [Mg2+]i. These
      results suggest that beta-adrenergic stimulation and cAMP play an important role
      in the regulation of [Mg2+]i in human erythrocytes.

PMID- 8268242
TI  - Ca2+ entry pathways activated by the tumor promoter thapsigargin in human
      platelets.
AB  - Thapsigargin-activated Ca2+ entry into platelets was examined in the presence of
      S-145, a thromboxane A2 receptor antagonist, to inhibit indirect effects by
      endogenously formed prostaglandin H2/thromboxane A2. With external Ca2+ present,
      0.2 microM thapsigargin caused a prompt increase in intracellular Ca2+
      concentration ([Ca2+]i) followed by a gradual increase. Pretreatment with 6
      microM wortmannin, a specific inhibitor of myosin light chain kinase, partly
      inhibited the increase in [Ca2+]i. In Ca(2+)-free EGTA buffer, thapsigargin
      induced a smaller increase in [Ca2+]i, and subsequent addition of Ca2+ to the
      buffer caused a further prompt increase in [Ca2+]i, demonstrating external Ca2+
      entry. Wortmannin only partly inhibited this entry of external Ca2+. The
      wortmannin-insensitive Ca2+ entry pathway remained open for more than 6 min in
      Ca(2+)-free buffer. On the other hand, when receptor agonists such as thrombin
      and U46619 were substituted for thapsigargin, activation of the wortmannin
      insensitive Ca2+ entry was transient (Hashimoto et al., J. Biol. Chem (1992) 267,
      17078-17081). In the presence of S-145 and wortmannin, thapsigargin stimulated
      phosphorylation of neither the 20-kDa myosin light chain nor the 47-kDa protein,
      a substrate of protein kinase C. These results suggest that thapsigargin induces
      external Ca2+ entry by two mechanisms: (1) a mechanism involving myosin light
      chain kinase; (2) a mechanism, not activated by receptor agonists, that is
      independent of the major protein kinases of platelets.

PMID- 8268244
TI  - Characterization of the alpha 1-adrenoceptor-mediated responses in perfused rat
      liver.
AB  - The present work aimed to further characterise the hepatic alpha 1-adrenergic
      actions by studying the influence of nutritional status and/or extracellular
      medium composition in the alpha 1-adrenoceptor-induced responses. The experiments
      were performed in a non-recirculating liver-perfusion system featuring continuous
      monitoring of vascular resistance, as well as the effluent perfusate changes in
      pO2, pCa2+, pK+ and pH. The alpha 1-adrenoceptor activation produced biphasic
      responses to most parameters studied. The acute phase lasted for about 3 min and
      it was followed by a phase of sustained stimulation that lasted as long as the
      receptor activation was maintained. Our data indicate that there is not a single
      pattern of alpha 1-adrenergic responses but variable patterns depending on the
      nutritional status and the experimental conditions. Gluconeogenic substrates
      alone produced reciprocal changes in the outflow perfusate pH and Ca2+ activity.
      The magnitude of these changes indicates that the diversity of alpha 1
      adrenoceptor responses are the result of the superposed effects of different
      rates of substrates and/or metabolites transport. The sustained alpha 1
      adrenoceptor stimulation produced extracellular acidification and increases in
      respiration, vascular resistance and Ca2+ release. These responses required
      physiological extracellular [Ca2+]. At low extracellular [Ca2+], the alpha 1
      adrenoceptor activation failed to acidify the extracellular medium, suggesting
      that receptor-induced H+ efflux demands normal rates of Ca2+ influx. The
      correlation between alpha 1-adrenergic-induced increase in O2 uptake and Ca2+
      release indicates that the increased energy production can be accounted for by
      the energy cost of Ca2+ release. The alpha 1-agonist concentration-response
      studies have shown significant differences in the [alpha 1-agonist]0.5 for each
      type of response, suggesting the existence of multiple alpha 1-adrenoceptor
      coupled signal-transduction pathways.

PMID- 8268243
TI  - Activation of phospholipase D in CHO cells transfected with the human epidermal
      growth factor (EGF) receptor: differential effects of protein kinase C activation
      and EGF.
AB  - Multiple intracellular signal transduction pathways, including phospholipases A2
      and D, can be activated by epidermal growth factor (EGF) in both a protein kinase
      C (PKC)-dependent and -independent manner. We investigated the activation of
      phospholipase D (PLD) by a PKC activator, phorbol myristate acetate (PMA) and by
      EGF in CHO cells transfected with the full-length EGF receptor. In cells labelled
      with arachidonic acid or linoleic acid, PMA activated a PLD, determined by
      formation of the transphosphatidylation product phosphatidylethanol in the
      presence of ethanol. A basal PLD activity was seen in linoleic acid-labelled
      cells but not in cells labelled with arachidonic acid. This basal activity was
      augmented by the protein phosphotyrosine phosphatase inhibitor vanadate and
      reduced by tyrosine kinase inhibition and was contributed to by PKC, as activity
      could not be elicited following prolonged exposure to phorbol ester, known to
      down-regulate some PKC isoforms. By contrast, EGF failed to stimulate formation
      of phosphatidylethanol in cells labelled with either fatty acid species. It is
      proposed that in the basal condition PKC-dependent PLD activation and protein
      tyrosine kinase phosphorylation are linked (possibly by a phospholipase C (PLC)
      mediated formation of diacylglycerol); EGF which activated a phospholipase A2
      (PLA2) but which failed to elicit PLC activation in these cells is without
      further effect on PLD.

PMID- 8268245
TI  - Involvement of protein kinase C in the interleukin 1 alpha-induced gene
      expression of matrix metalloproteinases and tissue inhibitor-1 of
      metalloproteinases (TIMP-1) in human uterine cervical fibroblasts.
AB  - The role of protein kinase C in the interleukin 1 (IL-1)-mediated production of
      pro-matrix metalloproteinases (proMMPs) and tissue inhibitor-1 of
      metalloproteinases (TIMP-1) in human uterine cervical fibro-blasts has been
      investigated. IL-1 and a protein kinase C activator, 12-O-tetradecanoylphorbol 13
      acetate (TPA) augmented the production of proMMP-1 (interstitial procollagenase),
      proMMP-3 (prostromelysin-1) and TIMP-1, but their effects were inhibited by the
      protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      dihydrochloride (H-7) and staurosporine in a dose-dependent manner. The
      suppressive effect of H-7 and staurosporine on the IL-1-induced production of
      proMMPs-1 and -3 and TIMP-1 resulted from the decrease in the steady-state levels
      of their mRNAs. When protein kinase C was down-regulated by treating the cells
      with a high level of TPA, the inductive effect of IL-1 upon proMMP-3 production
      was reduced considerably. These results indicate that protein kinase C mediates
      the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 at the
      pretranslational level in human uterine cervical fibroblasts. On the other hand,
      neither IL-1 nor TPA modulated the production of proMMP-2 (progelatinase A). Both
      IL-1 and TPA also accelerated the production of prostaglandin E2 (PGE2) by
      cervical fibroblasts. However, the treatment of the cells with staurosporine in
      the presence of IL-1 or TPA further augmented PGE2 synthesis, suggesting that the
      increased synthesis of PGE2 by IL-1 treatment is mediated via signalling pathways
      distinct from those of proMMPs-1 and -3 and TIMP-1.

PMID- 8268246
TI  - Reduced sodium pump activity in inositol-deficient HL-60 cells: no evidence of
      control by protein kinase C.
AB  - HL-60 cells were cultured in normal and inositol-deficient media. The inositol
      deficient cells showed reduced sodium pump activity, as measured by ouabain
      sensitive 86Rb+ uptake. The protein kinase C inhibitors staurosporine and H7 did
      not affect uptake in either normal or inositol-deficient cells. However, U73122,
      a steroidal inhibitor of phosphoinositidase C, inhibited uptake in both types of
      cells. Activators of protein kinase C had no effect on Rb+ entry. The inositol
      deficiency is not considered to affect the sodium pump by a mechanism involving
      diacylglycerol and protein kinase C.

PMID- 8268247
TI  - H7-resistant protein kinase C substrates in two-dimensional gels of proestrous
      rat anterior pituitary gland.
AB  - The presence of Ca(2+)-dependent and -independent protein kinase C (PKC)
      activities which were stimulated by phorbol-12,13-dibutyrate (PDBu) and sensitive
      to the kinase inhibitor staurosporine (IC50 values approx. 100 nM) was
      demonstrated in proestrous rat anterior pituitary gland. These PDBu-induced
      activities were completely abolished by the PKC-specific inhibitors Ro31-8220 and
      GF109203X (3 microM). The Ca(2+)-independent activity was more resistant (IC50 =
      61 microM) to the kinase inhibitor H7 than the Ca(2+)-dependent activity (IC50
      approx. 20 microM), however, this (unusual) resistance to H7 was not observed in
      the brain regions, hypothalamus and hippocampus. Possible substrates for the
      Ca(2+)-independent PKC in anterior pituitary were identified by two-dimensional
      gel electrophoresis and autoradiography following incubation in vitro with
      [32P]phosphate and 300 nM PDBu +/- 300 nM staurosporine or 30 microM H7. The
      phosphorylation of six proteins (16, 16, 25, 36, 65 and 69 kDa) was found to be
      stimulated by PDBu and inhibited by staurosporine, but not H7, in whole tissue,
      and another two such phosphorylated proteins (each 76 kDa) were observed in
      microsomal subcellular fractions. These phosphoproteins may be substrates for an
      H7-resistant PKC isoform previously shown to mediate a number of cellular
      responses in rat anterior pituitary gland.

PMID- 8268248
TI  - Regulation of agonist binding to A2A adenosine receptors: effects of guanine
      nucleotides (GDP[S] and GTP[S]) and Mg2+ ion.
AB  - Adenosine acts as a neuromodulator through at least two receptor subtypes, A1 and
      A2. A2 receptors have been further divided into A2A (high agonist affinity) and
      A2B (low agonist affinity) receptors. Both A1 and A2 receptors belong to the
      superfamily of guanine nucleotide-binding regulatory protein (G protein)-coupled
      receptors. A Gs protein couples the A2A receptor to the activation of adenylyl
      cyclase. In order to elucidate the mechanism of coupling between the A2A receptor
      and Gs, we studied the modulation by guanine nucleotides and divalent cations of
      agonist binding to the A2A receptor in rat striatal membranes, using [3H]CGS
      21680 as a selective high-affinity agonist. We demonstrated that in rat striatal
      membranes agonist binding to A2A receptors was modulated by guanine nucleotides.
      Both GDP and GTP inhibited [3H]CGS 21680 binding to rat striatal membranes with
      about equal potency. The nonhydrolyzable analogs, GDP[S] and GTP[S], were
      equipotent inhibitors and approx. 100-times more potent than GDP and GTP. Data
      from competition studies with labeled and unlabeled CGS 21680 when analyzed by
      nonlinear regression demonstrated the presence of two binding sites in rat
      striatal membranes with mean values for KD of 5.6 and 343 nM and Bmax of 200 and
      942 fmol/mg protein. The high-affinity binding site has the characteristics of
      the A2A receptor. In the presence both of (0.1 mM) GDP[S] and GTP[S], the KD
      values for the high-affinity site were increased severalfold, whereas the low
      affinity site was no longer detected in filtration assays. Dissociation studies
      revealed monophasic dissociation curves both in the absence and presence of 0.1
      mM GDP[S]. However the K-1 value increased in the presence of guanine nucleotide.
      We also showed that in bovine striatal membranes agonist binding to A2A receptors
      was modestly modulated by guanine nucleotides, suggesting differences of receptor
      Gs-protein-coupling a mechanism in different species. Divalent cations often
      increase agonist binding to different receptors, whereas Mg2+ ions play a role in
      regulating the initial steps of G-protein activation. We investigated the effects
      of divalent cations on [3H]CGS 21680 binding to the A2A receptor and determined
      the requirement of these cations to obtain the modulation of binding by guanine
      nucleotides. We found that millimolar concentrations of divalent cations were
      required to obtain an effective interaction between the A2A receptor and Gs. The
      high-affinity binding of [3H]CGS 21680 to the A2A receptor in rat striatal
      membranes was dependent on the presence of Mg2+ ions.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8268249
TI  - Hydrodynamic characterization and DNA-binding properties of the liganded and
      unliganded forms of the retinoic-acid receptor alpha from human HL-60 cells.
AB  - The hydrodynamic parameters of the retinoic-acid receptor from human myeloblastic
      leukemia HL-60 cells were accurately investigated. The ligand-bound retinoic-acid
      receptor (RAR) has a Stokes radius of 3.5 nm when analyzed by size-exclusion
      chromatography. A 53-kDa protein was detected by Western blot analysis using a
      polyclonal antibody directed against the F domain of hRAR alpha, in the fractions
      containing the 3.5-nm complex. Fractionation of a crude nuclear extract from HL
      60 cells, untreated with retinoic acid, yielded antibody-revealed material with
      Stokes radii ranging from 3.5 nm to 6 nm. From the hydrodynamic data, a molecular
      mass of 52 kDa was calculated for the liganded receptor, whereas no precise value
      could be deduced for the unliganded receptor form, since it dissociates rapidly
      into the 3.5-nm form. Gel-retardation experiments showed that the 3.5-nm form of
      hRAR alpha bound specifically to DNA, whereas binding of the unliganded receptor
      form was sharply reduced. These findings suggest that the unliganded inactive
      receptor form dissociates upon ligand binding and acquires a ligand-dependent DNA
      binding activity.

PMID- 8268250
TI  - Class I major histocompatibility complex antigens are not associated with the
      LH/CG receptor on ovine luteal cells.
AB  - We have examined the rotational dynamics of the luteinizing hormone (LH) receptor
      on day 10 intact ovine small luteal cells and isolated plasma membranes using
      polarized fluorescence depletion (PFD). This technique measures rotational
      correlation times which are proportional to the in-membrane volume of a protein
      and are useful for examining changes in protein size due to receptor aggregation
      or protein-protein interactions. Eosin isothiocyanate (EITC)-derivatized ovine LH
      (EITC-oLH) bound to the LH receptor on luteal cell plasma membranes had a
      rotational correlation time of 20 +/- 6 microseconds, while that for EITC-human
      chorionic gonadotropin (EITC-hCG)-occupied LH receptors was 46 +/- 13
      microseconds. Slower rotational times for EITC-oLH and EITC-hCG, 63 +/- 19 and 87
      +/- 20 microseconds, respectively, were obtained on intact ovine luteal cells.
      These results indicate that the LH receptor exists as a larger molecular mass
      complex when binding hCG than oLH, a difference which could be attributable to
      hCG-induced LH-receptor interaction with additional membrane protein(s). One
      candidate protein for such an interaction is the Major Histocompatibility Complex
      (MHC) Class-I antigen. However, the rotational correlation time of EITC-anti-MHC
      Class-I antibody (SBU I) Fab fragments was 247 +/- 34 microseconds, indicating
      that MHC Class I is located in complexes larger than those identified by EITC-OLH
      or EITC-hCG. Preincubation of plasma membranes with 1 nM unlabeled oLH or hCG had
      no significant effect on this rotational correlation time. Further, treatment of
      cells with SBU I had no affect on either basal or oLH-stimulated progesterone
      secretion. Thus it appears that the ovine luteal LH-receptor is not associated
      with MHC Class I and that antibody-induced aggregation of MHC Class I does not
      cause an LH-mimetic response.

PMID- 8268251
TI  - Further studies of the mixed acetals of nucleosides.
AB  - We reported in 1988 on a new nucleoside modification reaction: the exocyclic
      amino groups of (d)adenosine and (d)cytidine react rapidly at ambient temperature
      with acetaldehyde and alcohols to give stable mixed acetals (N-ethylethoxy
      acetal). NH2 + O = CH(CH3) + ROH-->NH-CH(CH3)-O-R + H2O. Here we report in detail
      on the occurrence of this reaction in very dilute aqueous solution (ie under
      biological conditions), on its mechanism and kinetics, on the mixed acetal
      formation with other aldehydes and other nucleic acid components, and on the
      question of whether these adducts are mutagenic.

PMID- 8268252
TI  - Mapping the promoter for subgenomic RNA synthesis on beet necrotic yellow vein
      virus RNA 3.
AB  - During infection of Tetragonia expansa leaves, RNA 3 of the quadripartite genome
      of beet necrotic yellow vein virus directs synthesis of a subgenomic RNA (RNA
      3sub) which corresponds to the 3'-terminal 600 residues of the RNA 3 molecule.
      Biologically active run-off transcripts have been prepared from full-length cDNA
      of RNA 3 cloned behind a bacteriophage T7-RNA polymerase promoter. RNA 3
      transcripts carrying deletions in the vicinity of the RNA 3sub initiation site
      were produced by site-directed mutagenesis at the cDNA level and then tested for
      their capacity to direct RNA 3sub synthesis in infected leaves. The cis-acting
      domain essential for normal levels of RNA 3sub production in planta (the 'core'
      promoter) did not extend in the 5'-direction beyond position -16 relative to the
      RNA 3sub transcription initiation site. The 3'-boundary of the core promoter
      domain was located somewhere between positions +100 and +208. Displacement of the
      promoter domain to an upstream site in RNA 3 produced a new subgenomic RNA
      starting at or near the predicted upstream site.

PMID- 8268253
TI  - Histones and histone genes in higher plants: structure and genomic organization.
AB  - The primary structure of the plant histone genes has been deduced from the
      comparison of the nucleotide sequences of 23 genes and 14 cDNAs from eight
      different species. These data confirmed the extreme conservation of histones H3
      and H4 in plant and animal kingdoms. Histone H2B is more variable than H2A and
      the histone H1 is the less conserved histone. Some interesting observations
      concerning the non-conserved regions of H2A and H2B in their extended C- and N
      terminal regions are reported. Only three plant histone genes were found to
      possess intervening sequences: one H1 gene and two H3.3 like genes. The most
      striking differences found between the two kingdoms are the absence from plant
      histone genes of the palindromic structure existing downstream of the animal
      genes and the fact that plant histone mRNAs are polyadenylated. This suggests
      that the post-transcriptional regulation of expression of histone genes is
      different in the two kingdoms. In plants the multiple copies of the histone genes
      are organized into multigenic families. In the complex genome of maize the
      multiple copies of the genes are highly dispersed on the genome.

PMID- 8268254
TI  - Why are quiescent mesophyll protoplasts from Nicotiana sylvestris able to re
      enter into the cell cycle and re-initiate a mitotic activity?
AB  - Mesophyll protoplasts of Nicotiana sylvestris incubated in an adequate culture
      medium re-enter very rapidly into the cell cycle and divide. The transition G0/G1
      is accompanied by a complete reversion of the program of gene expression. The
      program of the photosynthetic differentiated mesophyll cell is abolished whereas
      a new multipartite program of a highly stressed but ready-to-divide cell is
      established. Some genes encode proteins which structure suggests they may play
      key roles in these events. Most of the induced genes are under multiple controls:
      stress and/or development. Stress response and cellular re-organization might
      thus be closely related events that cannot be dissociated. It is probable that
      the re-entry of a protoplast into the cell cycle, ie the initial step of
      totipotency, closely depends on the coordinated activation of a set of genes that
      share common regulatory mechanisms.

PMID- 8268256
TI  - Mosaic disease induced by turnip yellow mosaic Tymovirus.
AB  - Mosaic disease is one of the most common consequences of infection of plants by
      viruses. Most such mosaics include islands of dark green tissue, which are normal
      in appearance, contain little or no virus and are resistant to superinfection at
      least for a period of weeks. The mosaic pattern that develops in successive
      expanded leaves of larger plants is variable and unpredictable. Therefore it has
      not been possible to investigate the early events in leaf primordia that lead to
      the formation of dark green tissue. Here we describe an experimental system which
      should allow the application of molecular techniques to the study of the nature
      of dark green tissue.

PMID- 8268255
TI  - Comparative epidemiology of three tropical whitefly-transmitted geminiviruses.
AB  - Spatial and temporal patterns of spread of African cassava mosaic, okra leaf curl
      and tobacco leaf curl viruses in West Africa, East Africa and India share some
      general characteristics. By comparing the results and running new analyses on
      available data, it is shown that the epidemiology of these viruses is controlled
      by the same key variables. For instance, spatial spread is characterised by
      strong border effects due to accumulation of whitefly vectors (Bemisia tabaci) on
      the wind-exposed field borders under the influence of the prevailing wind. This
      results in pronounced environmental gradients of disease. Temporal patterns of
      virus spread are driven by the sinusoidal fluctuation of temperature over the
      year which correspond with changes of whitefly populations.

PMID- 8268257
TI  - The TYMV tRNA-like structure.
AB  - The genomic RNA from turnip yellow mosaic virus presents a 3'-end functionally
      and structurally related to tRNAs. This report summarizes our knowledge about the
      peculiar structure of the tRNA-like domain and its interaction with tRNA specific
      proteins, like RNAse P, tRNA nucleotidyl-transferase, aminoacyl-tRNA synthetases,
      and elongation factors. It discusses also the biological role of this structure
      in the viral life cycle. A brief survey of our knowledge of other tRNA mimicries
      in biological systems, as well as their relevance for understanding canonical
      tRNA, will also be presented.

PMID- 8268258
TI  - The needs and hopes for an AIDS vaccine.
AB  - This article reviews the many difficulties met in the development of an effective
      vaccine against human immunodeficiency virus (HIV), including the considerable
      antigenic variability of the virus, its intracellular mode of transmission, its
      mucosal port of entry, and the persistent nature of the infection. Progresses in
      the development of prototype vaccines in animal models are discussed together
      with the results of initial clinical trials in human volunteers.

PMID- 8268259
TI  - Transient plant gene expression: a simple and reproducible method based on
      flowing particle gun.
AB  - Successful transient expression of beta-glucuronidase (Gus) and luciferase (Luc)
      in Nicotiana tabacum leaves was obtained after gene delivery by a simple and
      inexpensive particle gun. Takeuchi's biolistic process system was adapted to
      accelerate directly in a helium stream DNA-coated microprojectiles into intact
      plant leaf tissues. After bombardment of p70-omega-59Gus construction
      (duplication of the CaMV 35S enhancer), variability inherent to the bombardment
      procedure was observed in Gus activity measurements between replicate samples. We
      therefore included an internal standard (35S-Luc) in each bombardment, allowing
      an accurate, sensitive and reproducible comparison of the effective strength of
      different Gus-reporter constructs based on Gus/Luc ratio measurements.

PMID- 8268260
TI  - The conserved nonanucleotide motif of the geminivirus stem-loop sequence promotes
      replicational release of virus molecules from redundant copies.
AB  - Recombinant plasmids containing head-to-tail copies of different coat-protein
      replacement genomes of wheat dwarf virus (WDV) were used to study the mechanism
      leading to the release of replicating unit-length molecules in suspension culture
      cells of Triticum monococcum. For plasmids bearing two complete genomes, the
      viral unit bracketed by the two large intergenic regions (LIR) becomes
      preferentially released. Addition of a third copy of the LIR on the inoculum
      plasmid is necessary for release of both WDV genomes with the same efficiency.
      Using plasmids containing a single viral genome flanked by two different hybrid
      LIRs, we show that the sequence TAATATTA, which is part of the conserved
      geminivirus nonanucleotide motif of the potential hairpin structure, is the
      region of the LIR within which the release of unit-length molecules occurs.
      Moreover, the data suggest that this release results primarily from rolling
      circle replication, also in situations where intramolecular homologous
      recombination is simultaneously possible.

PMID- 8268261
TI  - Coat protein stimulates replication complexes of alfalfa mosaic virus to produce
      virion RNAs in vitro.
AB  - Viral replication complexes (RCs) were gradient-purified from cowpea mesophyll
      protoplasts 21 h after inoculation with alfalfa mosaic virus. These membranous
      structures incorporate [32P]UMP into double- and single-stranded RNAs in the
      absence of added template. When coat protein is added prior to the reaction the
      incorporation in both RNA fractions is stimulated several times. Part of the
      single-stranded product RNAs are released from the RCs. The stimulation of
      incorporation in high molecular mass RNAs by coat protein can be mimicked only to
      a certain extent by addition of a ribonuclease inhibitor or of an excess of viral
      RNA prior to the reaction. This shows that the coat protein is not only
      protecting the product of the RCs against degradation by ribonuclease, but that
      it is stimulating the synthesis and release of viral RNAs from RCs as well. This
      leads to the hypothesis that with alfalfa mosaic virus some coat protein is
      necessary for the release of messenger RNA from the RC. The hypothesis explains
      why the viral genome RNAs, although they are of messenger polarity, cannot start
      a replication cycle in the absence of coat protein: RCs containing the parental
      RNAs could be formed but no amplification of them could take place since no
      messenger RNAs needed for the production of viral polymerase proteins would be
      released into the cytoplasm.

PMID- 8268262
TI  - Efficient pathogen-derived resistance induced by integrated potato virus Y coat
      protein gene in tobacco.
AB  - The coat protein (CP) gene from potato virus Y (Hungarian isolate, PVY-H) was
      engineered into Agrobacterium tumefaciens binary vector for expression in
      different tobacco lines. Three different Nicotiana tabacum breeding lines were
      transformed and the integration of the CP gene was confirmed by PCR technique
      using genomic DNA preparations. The transcription and expression of the
      integrated CP gene was detected by Northern and Western blots. Pathogen-derived
      resistance was demonstrated by inoculation of the R1 progeny of the transformed
      lines with purified PVY-H. The efficiency of protection varied between different
      transgenic plants ranging from almost complete to no protection. Five CP
      expressing tobacco lines were resistant to challenge infection with PVY-H as
      indicated by attenuation or absence of symptom development associated with
      reduction or lack of detectable virus accumulation. Data from Western blots
      showed that there is no correlation between the level of the expressed CP and the
      extent of protection. This suggests that the mechanism of the observed resistance
      is independent of the level of CP accumulation in the transgenic tobacco plants.

PMID- 8268263
TI  - Set-up and present indications: video-assisted thoracic surgery.

PMID- 8268265
TI  - Use of lasers in thoracoscopy.
AB  - The ND:YAG surgical laser is a safe and effective method for resection of
      pulmonary nodules using VATS. It may be used as the primary resecting tool or as
      an adjunct to endoscopic stapling techniques to provide optimal pulmonary tissue
      preservation, and to avoid injury to the lung from inappropriate stapler
      applications. Thoracoscopic laser resection is particularly suited for deep
      lesions and for surface nodules where staplers are inadequate. Laser ablation of
      bullous disease using thoracoscopy offers a minimally invasive method of treating
      symptomatic patients with complications from dominant bullae.

PMID- 8268264
TI  - Role of thoracoscopy in the diagnosis and management of pleural diseases.

PMID- 8268266
TI  - Pediatric thoracoscopy.

PMID- 8268267
TI  - Credentialing issues and complications of video-assisted thoracic surgery.

PMID- 8268268
TI  - Esophageal surgery by the thoracoscopic approach.

PMID- 8268269
TI  - Thoracoscopic management of pericardial disease.

PMID- 8268270
TI  - Video-assisted pulmonary lobectomy.

PMID- 8268271
TI  - Anesthetic considerations for video-assisted thoracic surgery.
AB  - VATS presents new challenges to the surgeon and anesthesiologist. Although simple
      diagnostic procedures on the pleura can be performed with local, regional, or
      general anesthesia with conventional ventilation, more complicated VATS requires
      general anesthesia with one-lung ventilation. Several techniques can be used to
      obtain one-lung anesthesia and should be tailored to the patient, proposed
      procedure, and comfort level of the anesthesiologist. The overall anesthetic
      management of these patients is similar to those having posterolateral
      thoracotomies and includes the ability of the anesthesiologist to react to rapid
      changes in the procedure as well as the overall condition of the patient.

PMID- 8268272
TI  - Thoracoscopic management of pulmonary blebs and bullae.

PMID- 8268273
TI  - Thoracoscopy and its role in mediastinal disease and sympathectomy.

PMID- 8268274
TI  - How should acute hepatic drug effects be studied epidemiologically?

PMID- 8268275
TI  - Trends in nonsmoking lung cancer.

PMID- 8268276
TI  - Do trans fatty acids in margarine and other foods increase the risk of coronary
      heart disease?

PMID- 8268277
TI  - The increased risk of hospitalizations for acute liver injury in a population
      with exposure to multiple drugs.
AB  - We conducted a nested case-control study to estimate and compare the relative
      risks for hospitalizations for newly diagnosed acute liver injury associated with
      the use of non-steroidal antiinflammatory drugs (NSAIDs) and other hepatotoxic
      drugs and their interaction. The source population comprised 228,392 members of
      the Saskatchewan Health Plan from 1982 to 1986. We used hospital records and the
      databases of the Department of Health. Thirty-four cases with confirmed liver
      injury were hospitalized. We randomly selected 500 controls from the source
      population. Crude risks ranged from 1 case per 100,000 prescriptions in current
      users of methyldopa, ampicillin, or NSAIDs to 14 cases per 100,000 prescriptions
      in current users of erythromycin estolate. The age-adjusted odds ratios for
      current users of NSAIDs was 1.8 [95% confidence interval (CI) = 0.8-3.7] and for
      other hepatotoxic drugs 5.9 (95% CI = 2.8-12.4). The adjusted relative excess
      risk due to the interaction between current exposure to both categories of drugs
      was 3.6, accounting for 31% of the cases of acute liver injury among those with
      exposure to both types of drugs. We conclude that the risk of hospitalization for
      acute noninfectious liver injury is different among users of various individual
      potentially hepatotoxic drugs. Concomitant current exposure to two or more drugs
      increases this risk above what would merely be expected from the sum of the
      individual risks.

PMID- 8268278
TI  - Indirect estimates of lung cancer death rates in Italy not attributable to active
      smoking.
AB  - We used a model, originally applied in the context of occupational cohort studies
      to evaluate confounding from smoking, to estimate lung cancer death rates in the
      Italian population not attributable to active smoking (background rates).
      Relevant parameters were the percentages of current and former smokers in the
      population, as derived from national interview surveys, and rate ratios for lung
      cancer and smoking. We studied differences over time (1956-1958 to 1987-1989) and
      place (urban/rural) in the background lung cancer death rates while allowing for
      changes in the average daily amount of tobacco consumption and in duration of
      smoking. We applied two functions proposed by Whittemore to obtain rate ratios
      for smokers: one assumes a linear relation between cumulative number of
      cigarettes smoked and lung cancer death rates; the other is closer to the
      multistage carcinogenesis theory. All our calculations indicate that the
      estimated background rates increased in Italy from the period 1956-1958 to the
      period 1987-1989; the increase was stronger in males than in females. In 1980
      1982, higher background rates were observed in heavily urbanized areas than in
      rural areas. The results did not change when we considered cohort effects in
      smoking prevalence and when the key parameters were perturbed in a sensitivity
      analysis. It appears that factors other than smoking play an important role in
      causing lung cancer in Italy.

PMID- 8268279
TI  - Diet and coronary heart disease: a case-control study in Athens, Greece.
AB  - We conducted a case-control study in Athens, Greece, between January 1990 and
      April 1991 to examine the association between diet and coronary heart disease.
      The case series comprised 329 patients with electrocardiographically confirmed
      first coronary infarct or a first positive coronary arteriogram, or both, who
      were admitted to a major teaching hospital during a 16-month period. Controls
      were 570 patients admitted to the same hospital for minor conditions believed to
      be unrelated to nutrition. Total energy intake was inversely associated with
      coronary heart disease risk, a quintile energy increase corresponding to a
      relative risk of 0.96. After controlling for total energy intake, dietary fat was
      positively related to coronary heart disease, and total carbohydrates were
      negatively related to coronary heart disease, the nutrient-specific relative
      risks for a quintile increase being 1.19 (95% confidence interval = 0.96-1.48)
      and 0.81 (95% confidence interval = 0.67-0.97), respectively. Major fat
      components (saturated, monounsaturated, and polyunsaturated fat) did not appear
      to have differential risk implications for coronary heart disease; however,
      cooking with margarine was associated with an increased relative risk (1.87; 95%
      confidence interval = 0.82-4.28). Dietary proteins, cholesterol, and vitamin C
      were not associated with coronary heart disease.

PMID- 8268280
TI  - Measures of effect based on the sufficient causes model. 2. Risks and rates of
      disease associated with a single preventive agent.
AB  - We considered a simple formulation of the sufficient causes model, in which a
      preventive agent exerts its effect by preventing a sufficient cause of the
      disease from occurring, while leaving another sufficient cause unaffected. In a
      group unexposed to the preventive agent, a case of the disease is caused by
      whichever of the two sufficient causes occurs alone or first in the subject.
      Among exposed subjects, the preventive agent prevents only the cases of disease
      in which the sufficient cause it blocks would have occurred alone, not the cases
      in which the other sufficient cause also occurs during the study period. The
      proportion of subjects who would avoid the disease if exposed to the preventive
      agent is the risk difference. The risk difference varies over time, even when the
      rates of occurrence of the sufficient causes are constant. It increases to a
      maximum and then declines, as the subjects who have avoided the disease because
      of the agent later contract the same disease because of exposure to the other
      sufficient cause. This maximum and the time at which it occurs are readily
      computed from the incidence rates of disease among exposed and unexposed
      subjects.

PMID- 8268281
TI  - Relation of the crude relative risk of a disorder to relative risks in strata of
      a "susceptible" variable.
AB  - If tau d is the relative risk of a disorder in the entire population, and tau d,i
      is the relative risk of the disorder in i = 1, ... m strata, then one may show
      readily that tau d = sigma ci tau d,i, where ci is the product of two terms tau
      i, the risk ratio of being in the ith stratum, and pi,unexp d, the proportion of
      those with the disorder and unexposed who are in the ith stratum. This
      formulation is of primary interest in epidemiology when relative risks are
      available on one or only some strata of a variable that itself may be affected by
      exposure (what one may define as a "susceptible" covariate) such as mortality or
      hospitalization. Although relative risks within strata of such a variable may be
      of some intrinsic clinical interest, only the risk ratio unstratified on such a
      variate may be pertinent to a causal effect (unlike the case for nonsusceptible
      variables such as sex, age, etc). In some instances, as for birth defects, one
      may have data from a few strata or only one (for example, livebirths) of a
      susceptible covariate (for example, conceptus viability). But one may still be
      able to draw useful inferences about tau d, the risk ratio in the entire
      population, because if tau d,i > or = 1/ci (or k/ci), one may conclude that tau d
      is, at least, greater than 1.0 (or k). Similarly, a study of a disorder limited
      to hospitalized cases and controls may enable investigators to infer, using the
      same criterion, a positive association in the entire population despite the
      presence of hospitalization bias of the type described by Berkson.

PMID- 8268282
TI  - Moderate alcohol consumption and the risk of endometrial cancer.
AB  - In a multicenter case-control study that included 400 cases and 297 controls, we
      examined the relation of moderate alcohol consumption to risk of endometrial
      cancer. We estimated average weekly intake of alcohol during adulthood from the
      reported frequency of intake of beer, wine, and liquor. The relative risk of
      endometrial cancer was 0.82 (95% confidence interval = 0.6-1.2) among women who
      drank, compared with lifelong abstainers. The weak protective effect of alcohol
      was due to a stronger inverse association among young women (< 55 years). In
      young women, the age-adjusted relative risks for three levels of drinking ( < 1,
      1-4, > 4 drinks per week), from lowest to highest, were 0.78, 0.64, and 0.41
      compared with nondrinkers. The risk estimates were not materially altered after
      adjustment for a variety of factors related to alcohol intake and to low risk of
      the disease (for example, smoking, oral contraceptive use, low body mass index,
      increased physical activity). The protective effect of alcohol could not be
      attributed to one particular type of alcohol-containing beverage, but beer
      appeared to have the most pronounced effect. These results suggest an inverse
      association between moderate alcohol consumption and endometrial cancer risk
      among young women, but support for a causal association is qualified and requires
      confirmation.

PMID- 8268283
TI  - Dietary vitamin C and serum lipids in black and white girls.
AB  - We examined the cross-sectional relation of dietary vitamin C intake to serum
      lipids in 1,825 preadolescent black and white girls. Dietary vitamin C intake
      exclusive of supplement use, determined by 3-day diet record, appeared unrelated
      to total serum cholesterol, high-density lipoprotein-cholesterol, low-density
      lipoprotein-cholesterol, and triglyceride levels. Because other investigators
      have demonstrated an inverse association between vitamin C and total serum
      cholesterol in individuals with elevated total serum cholesterol levels, we
      analyzed the subgroup of 285 girls (142 blacks and 143 whites) with total serum
      cholesterol levels > or = 200 mg per dl. Multivariate analyses of this subgroup,
      which adjusted for saturated fat, polyunsaturated fat, monounsaturated fat,
      cholesterol, fiber, and energy intake and for body mass index, demonstrated
      negative association between vitamin C intake and total serum cholesterol. In
      girls with total serum cholesterol levels > or = 200 mg per dl, each 100 mg per
      day increase in dietary vitamin C intake (ranges 13-373 and 14-242 mg per day for
      blacks and whites, respectively) was associated with a total serum cholesterol
      decrease of 4 mg per dl (95% confidence limits = -10.34, 2.77) in blacks and 13
      mg per dl (95% confidence limits = -22.99, -2.68) in whites. If the observed
      association is causal and generalizable, our results suggest that increased
      vitamin C intake could play an important role in the cholesterol homeostasis of
      females with elevated total cholesterol levels.

PMID- 8268284
TI  - Is survival among women diagnosed with breast cancer influenced by family history
      of breast cancer?
AB  - In this study, we examine the association between having a family history of
      breast cancer and survival after diagnosis with breast cancer. Data for this
      study were from the Utah Population Database, a linked database consisting of
      genealogy data of Mormon pioneer families, Utah Cancer Registry data, and Vital
      Statistics data. We observed that women who had a mother with breast cancer were
      more likely to die of any cause than women without a mother with breast cancer
      [hazard rate ratio (HRR) = 1.36, 95% confidence limits (CL) = 1.04, 1.79], as
      were women with over 30 female relatives with breast cancer (HRR = 1.69, 95% CL =
      1.16, 2.45). Similar findings were observed for women dying of breast cancer.
      Other indicators of family history were not associated with survival except
      within specific age groups. Women diagnosed with breast cancer at age 50 or
      before had poorer survival if they had a family history of breast cancer.
      Relative risk estimates were 1.54 (95% CL = 0.98, 2.41) for first degree
      relative, 1.55 (95% CL = 0.87, 2.78) for mother, and 2.65 (95% CL = 1.23, 5.74)
      for more than 30 female relatives with breast cancer.

PMID- 8268285
TI  - Maternal prior pregnancy loss and the sex ratio among infants with sudden infant
      death syndrome.
AB  - It has been reported that the offspring of human leukocyte antigen (HLA)
      compatible parents may have a high male/female sex ratio. To study the hypothesis
      that parental HLA compatibility is related to sudden infant death syndrome
      (SIDS), I conducted a population-based case-control study using 1982-1990 linked
      Washington State birth and death certificate data to compare the sex ratio of
      SIDS cases and controls. SIDS cases were identified by the International
      Classification of Diseases, 9th revision, CM code 798.0, on the death
      certificate, and four controls born in the same year as the case were randomly
      selected for each case. I categorized the infants according to maternal parity
      and history of pregnancy loss. There was a high risk of SIDS in males relative to
      females among first liveborn infants whose mothers had had two or more prior
      pregnancy losses (odds ratio = 7.6, 95% confidence interval = 1.5-39). I had
      hypothesized a priori that this group would have the largest proportion of
      infants of HLA-compatible parents. No similar association was observed among
      infants with a prior liveborn sibling. In addition to the findings from two
      previous studies, this finding provides further evidence that parental HLA
      compatibility may be related to the risk of SIDS in offspring.

PMID- 8268286
TI  - Casual inference.

PMID- 8268287
TI  - Control of confounding requires specification of risk periods.

PMID- 8268288
TI  - Authors should be expected to elucidate policy implications of empirical data.

PMID- 8268289
TI  - A delicate subject.

PMID- 8268290
TI  - Estimation and the nature of controls in birth defect studies.

PMID- 8268291
TI  - Butadiene epidemiology re-interpreted, again.

PMID- 8268292
TI  - Determining the hazards of work place chemicals.

PMID- 8268293
TI  - Spurious bias in the attribution of lung cancer as a cause of death.

PMID- 8268294
TI  - [Import of cytoplasmic lysyl tRNA in mitochondria of baker's yeasts: prospects
      for study in vivo and in vitro].
AB  - To study the mechanisms of targeting tRNA(CUULys) from the cytoplasm into the
      mitochondrial compartment of the yeast cells, two test systems have been
      developed. The in vivo system based on the electroporation of intact yeast cells
      was used to introduce labelled tRNAs into the cytoplasm; however, only
      tRNA(CUULys) was found in the mitochondrial compartment. The in vitro import of
      this tRNA into isolated mitochondria required the presence of ATP and soluble
      cellular proteins in the reaction mixture. Two protein fractions were found to be
      necessary to direct the import in vitro. The first one had a high heparin-binding
      affinity, while the other one was not retained on heparin-Sepharose.
      Aminoacylation of the tRNA(Lys) before the transport and/or addition of the
      correspondent lysyl-tRNA synthetase to the in vitro system increased the
      efficiency of the import, but the protein fraction with heparin-binding
      properties is still required. The unmodified transcripts of the tRNA(CUULys) gene
      were shown to be able to be transported into isolated yeast mitochondria.

PMID- 8268295
TI  - [The effect of phosphorylation on catalytic function of muscle pyruvate
      dehydrogenase complex].
AB  - It has been shown that phosphorylation of the pyruvate dehydrogenase complex from
      pigeon breast muscle by endogenous ATP-dependent protein kinase suppresses the
      substrate conversion in the pyruvate: acceptor oxidoreductase reactions and
      nonoxidative reactions monitored by pyruvate decline in the absence of CoA and
      NAD. To identify the catalytic step blocked by phosphorylation, CD spectroscopy
      was used which revealed the appearance and decay of the charge transfer complex
      between component E1 and thiamine pyrophosphate during the enzymatic reaction.
      Phosphorylation of the pyruvate dehydrogenase complex while lowering the affinity
      for thiamine pyrophosphate does not preclude the formation of holo-E1 but
      inhibits its interaction with pyruvate. Phosphorylated pyruvate dehydrogenase,
      like the dephosphorylated enzyme, reacts with 2-hydroxyethyl thiamine
      pyrophosphate in half of the active sites. In the presence of deacylating agents
      (CoA or dithiothreitol) all the sites are reactive. A conclusion is drawn that
      the alternating functioning of the active centers is preserved in reductive
      acetylation of the acceptor substrates by phospho-E1.

PMID- 8268296
TI  - [Oxidative phosphorylation uncoupling by fatty acids in liver and muscle
      mitochondria].
AB  - Pathways and mechanisms of oxidative phosphorylation uncoupling by long-chain
      fatty acids in liver and muscle mitochondria are considered. A conclusion is
      drawn that there exist at least three different pathways of uncoupling by fatty
      acids, namely: (i) a Ca(2+)-dependent cyclosporin A-sensitive pathway; (ii)
      uncoupling which is inhibited by carboxyatractylate or other inhibitors of the
      ADP/ATP-antiporter, (iii) uncoupling due to the low protonophoric activity of
      fatty acids.

PMID- 8268297
TI  - [A lysoamidase bacteriolytic complex. 1. Determination of the nature of
      interaction of enzymes and the polysaccharide, included in the complex].
AB  - The polysaccharide component of the bacteriolytic enzymatic complex "lysoamidase"
      (M(r) 1300 kDa) has been found to contain negatively charged ionic groups and can
      electrostatically interact with some enzymes within the complex. At pH 8.0
      optimal for bacterial lysis, such interaction promotes the stabilization of
      bacteriolytic enzymes, increasing their half-inactivation temperature by 8
      degrees and their stability upon storage by 40%. The polysaccharide decreases the
      thermal stability of phosphatase but has no stabilizing effect on the
      metalloprotease.

PMID- 8268298
TI  - [Phosphorylation of cytochrome P-450SCC by protein kinase C. The protective
      effect of adrenodoxin and cytochrome b5].
AB  - Cytochrome P-450scc from bovine adrenal cortex mitochondria was shown to be
      selectively phosphorylated by protein kinase C. The amino acid residues most
      accessible to phosphorylation by protein kinase C are located in the N-terminal
      sequence of cytochrome P-450scc. Adrenodoxin and cytochrome b5 protect cytochrome
      P-450scc from phosphorylation, this effect being dependent on the protein
      concentration.

PMID- 8268299
TI  - [The functional status of the xenobiotic biotransformation system in poisoning
      animals with diphenylamine and N-nitrosodiphenylamine].
AB  - The state of the xenobiotic biotransformation system has been studied after a
      single per os administration of diphenylamine (DPA) and N-nitrosodiphenylamine
      (NDPA) to male albino rats. Intoxication of animals with NDPA induced
      unidirectional and similar changes in the functional states of the both stages of
      the xenobiotic metabolism. There was an increase in the total content of
      cytochrome P-450 and the activity of NADPH-cytochrome P-450 reductase as well as
      a marked elevation of activity of microsomal glutathione S-transferase. This was
      paralleled with the induction of activity of individual isoenzymes of the
      multifunctional family of rat liver cytosol glutathione S-transferases and
      increased activity of glutathione reductase. Unlike NDPA, DPA affected only the
      second stage of the xenobiotic biotransformation by stimulating the activity of
      both membrane-bound and soluble glutathione S-transferases. In both cases the
      intoxication was attended by an increase in the number of SH-groups unbound to
      the protein. It was assumed that the different response of the xenobiotic
      biotransformation system to DPA and NDPA may be due to the appearance of a N
      nitroso group in the NDPA molecule.

PMID- 8268300
TI  - [Prostaglandin H synthase. Chemical modification of histidine residues in various
      forms of the enzyme by diethylpyrocarbonate].
AB  - Prostaglandin H synthase (PGHS) as apo- and holoenzyme and the enzyme inactivated
      during the conversion of arachidonic acid into prostaglandin H2 has been modified
      by diethyl pyrocarbonate (DEPC). DEPC (40 mol/l mol protein) rapidly, but
      quantitatively differently interacted with the three forms of the enzyme (pH 6.0,
      25 degrees C). The exhausted reaction with DEPC corresponded to modification of
      seven histidine residues in apo-PGHS and four residues in holo-PGHS. All of the
      18 histidine residues were available for modification in the enzyme inactivated
      during the catalysis. The modification of apo-PGHS was accompanied by a concerted
      loss of the combined cyclooxygenase plus peroxidase and peroxidase activities.
      The velocities of the tryptic cleavage of the three forms of the enzyme into the
      33 and 38 kDa polypeptides were essentially different, but the modification of
      each enzyme form did not affect the velocity of its cleavage. Two of the three
      histidine residues essential for the interaction with the heme within the 38 kDa
      fragment might be His-309 and His-388. Based on the comparison of availability
      for the reaction with DEPC of all the 18 histidine residues in the enzyme
      molecule inactivated by the interaction with arachidonic acid and on the
      abnormally high velocity of the tryptic cleavage of this form of PGHS, a
      hypothesis has been put forward about the fast and dramatic changes in the
      protein structure in the course of catalysis.

PMID- 8268301
TI  - [DNA-dependent RNA-polymerase II from human placental nuclei].
AB  - The procedure for isolation and purification of RNA polymerase II from human
      placenta nuclei is described. The sensitivity of the enzyme to alpha-amanitin,
      bivalent cations, ionic strength and glycerol concentration in vitro has been
      studied. Eleven subunits of the RNA polymerase II molecule have been identified
      by gel electrophoresis. An optimal RNA polymerase II assay mixture has been
      developed.

PMID- 8268302
TI  - [Redistribution of rabbit blood serum lipoproteins, caused by a one-time
      administration of cholesterol].
AB  - The redistribution of rabbit blood serum lipoproteins following 24-hr incubation
      of the sera at 37 degrees C and after a single injection of cholesterol (0.2
      g/kg) was studied. In both cases there was an increase in the intermediate
      density (IDL) and low density lipoproteins (LDL) and a sharp decrease in very low
      density lipoproteins (VLDL). The proportion of the total fraction of high density
      lipoproteins (HDL) decreased also. The redistribution of the HDL subpopulations
      against the background of the HDL decline after a single cholesterol dose seems
      to be due to a relative increase in HDL3 and a decrease in HDL2. The HDL
      transformation during heat incubation of control sera was accompanied by HDL3
      conversion into HDL2. These data suggest that a single cholesterol dose and heat
      incubation of blood sera stimulate the direct and reverse cholesterol transport.
      In isolated sera these processes subside gradually. The inhibition mechanism
      entails the depletion of the lipoprotein system for chylomicrons and VLDL and
      exhaustion of HDL2. The restoration of the functional potential of the blood
      lipid-transporting system needs the exchange between lipoproteins and tissues.

PMID- 8268303
TI  - [Features of structural organization of chromatin from various sources].
AB  - The conformational peculiarities of DNA and histones of chromatins of different
      origin have been studied using circular dichroism (CD). The chromatins were
      isolated from pigeon brain, rat thymus and liver, ascitic hepatoma 22A, C3HA
      mouse liver, pigeon erythrocytes and sea urchin sperm. The functional
      peculiarities of the chromatins were found to correlate with their compactness
      and the nucleosomal DNA repeat length. Analysis of chromatin CD spectra made it
      possible to define the degree of DNA compactness in oligonucleosomes and the
      secondary structure of their linker histones of the H1 family. It was found that
      in low ionic strength solutions the structures of chromatosomes are formed in
      erythrocyte and thymus chromatins, but not in sea urchin sperm chromatin. The
      size of the compact part of the DNA in the nucleosomes of transcriptionally
      active chromatins of brain and ascitic hepatoma 22A are less than the length of
      the DNA of the core particles under identical conditions. The secondary structure
      of the H1 histone from sea urchin sperm chromatin, unlike other linker histones
      of the H1 family, contains an additional alpha-helical segment in the C-terminal
      part. Analysis of structural changes of the both chromatin components during
      condensation of their oligonucleosomal chains with an increase in the ionic
      strength has been carried out.

PMID- 8268304
TI  - [Human thyroid gland DNA methylase in nodular and diffuse goiter].
AB  - The heterogeneity and some properties of DNA-methylases isolated from
      nonmalignant human thyroid formations--nodular and diffuse goiters--have been
      studied. Isoelectrofocusing of methylase preparations produced 6-7 distinct
      activity peaks distinguished by pI, activity towards Ca2+ and Mg2+, sensitivity
      towards dithiothreitol and capacity to methylase cytosine into mono-, di- and
      tripyrimidine blocks in vitro. The degree of DNA methylation in vivo depended on
      the origin of of the goiter. Analysis of several methylase fractions by two
      dimensional electrophoresis performed according to O'Farrell revealed the
      presence of major polypeptides having similar molecular masses (approximately 36
      kDa). Besides the major component, all the preparations under study contained 6
      10 characteristic minor components. The data obtained are suggestive of a
      structural and functional heterogeneity of human methylases.

PMID- 8268305
TI  - [The effect of inhibitors of the Q-cycle on cyano-resistant oxidation of malate
      by rat liver mitochondria in the presence of menadione].
AB  - Based on the inhibitor analysis data, it has been assumed that the Q-cycle plays
      a role in the cyano-resistant malate oxidation induced by menadione (90 microM)
      in rat liver mitochondria. The extent of involvement of Q-cycle transmitters in
      the cyano-resistant respiration of mitochondria is determined by the mode of the
      electron supply into the Q-cycle. In the presence of dicumarol, i.e., under
      conditions when CoQ and menadione are reduced by NADH-quinone reductase, the bulk
      of the electrons pass through the o-center of the Q-cycle. Myxothiazole inhibits
      the respiration by 70-80%, while antimycin--by only 20-30%. In the presence of
      myxothiazole and antimycin menadione oxidizes cytochrome b. In the presence of
      rotenone, when menadione is reduced by DT-diaphorase, the rate of cyano-resistant
      respiration decreases approximately twofold; its sensitivity towards myxothiazole
      and antimycin drops down to 40%. In the absence of rotenone and dicumarol the Q
      cycle does not participate in the cyano-resistant respiration which under these
      conditions is insensitive either to myxothiazole or to antimycin. It is concluded
      that the mechanism of cyano-resistant respiration changes with an alteration in
      the rates of quinones K3 and CoQ reduction. The mechanism of cyano-resistant
      respiration is also controlled by the medium tonicity. A reduction in the medium
      tonicity decrease the participation of the Q-cycle and, correspondingly, the
      sensitivity of the cyano-resistant respiration towards myxothiazole and
      antimycin.

PMID- 8268306
TI  - [Ganglioside lactones in human stomach and breast tumors].
AB  - Ganglioside lactones absent in homologous normal tissues have been found in
      minute amounts in human gastric and mammary tumours. In mammary gland tumours
      only the ganglioside GM3 lactone has been identified. Gastric tumours also
      contain the GM3 lactone; in one case a ganglioside GD3 lactone was identified.

PMID- 8268307
TI  - [Conjugation of classic Bowman-Birk soy inhibitor with a copolymer of ethylene
      oxide and propylene oxide].
AB  - A classical soybean inhibitor of the Bowman-Birk type (BBI) with a copolymer of
      ethylene oxide and propylene oxide (PE) has been synthesized. The BBI-PE
      conjugate contain five covalently bound polymeric chains per one protein molecule
      and retains its capacity to inhibit trypsin (Ki = 10(-10) M), alpha-chymotrypsin
      (Ki = 7 x 10(-8) M) and human granulocyte elastase (Ki = 3 x 10(-8) M). The
      preservation of the antiproteinase activity in the antichymotrypsin center
      creates a prerequisite for the manifestation of the anticarcinogenic effect of
      the inhibitor.

PMID- 8268308
TI  - [Bowman-Birk soy inhibitor as an affinity ligand for isolating leukocyte
      elastase. Inhibition of elastin hydrolysis, catalyzed by leukocyte elastase].
AB  - A one-step procedure for human leukocyte elastase purification using an affinity
      adsorbent based on protein soybean Bowman-Birk proteinase inhibitor has been
      developed. The leukocyte elastase was purified 70-fold with a 70-100% yield. The
      enzyme preparations did not contain cathepsin G and displayed a high specific
      activity. The soybean Bowman-Birk type inhibitor effectively inhibited the
      elastin hydrolysis by leukocyte elastase both when the enzyme and the inhibitor
      were simultaneously added to the substrate and after preliminary elastase
      adsorption on elastin. The inhibitory effect was preserved at high degrees of
      elastin hydrolysis.

PMID- 8268309
TI  - [Structure and regulation of the activity of muscle phosphorylase kinase].
AB  - Phosphorylase kinase is the key enzyme in the control of glycogen metabolism in
      skeletal muscles, the heart and the liver. The quaternary structure of the
      enzyme, the primary structure of the enzyme subunits as well as the kinetic
      properties and regulation of the skeletal muscle enzyme activity by covalent
      modification, phosphorylation and some physiological effectors (Ca2+, calmodulin,
      troponin C) are reviewed.

PMID- 8268310
TI  - [Participation of tocopherol and its analogs in lipid peroxidation processes and
      electron transport in rat liver mitochondria in vivo].
AB  - The effects of vitamin E and its analogs--alpha-tocopheryl acetate with a
      shortened up to six carbon atoms side chain carrying a saturated and an
      unsaturated bonds at the chain terminus, alpha-tocopherol and alpha-tocopheryl
      quinone devoid of the side chain--on the rate of malonic dialdehyde formation,
      the diene conjugate and total lipid content in the liver as well as the activity
      of the respiratory chain enzymes--succinate--and NADH-dehydrogenase, succinate-
      and NADH-ubiquinone reductase, as well as the vitamin E and ubiquinone content in
      the liver mitochondria of vitamin E-deficient rats in vivo have been
      investigated. It has been found that alpha-tocopheryl acetate with a shortened
      (up to C6) side chain carrying a saturated bond at the chain terminus is the most
      effective analog of tocopherol. Further reduction of the tocopherol side chain or
      tocopherol conversion into quinone causes a decrease in their tocopherol
      activity.

PMID- 8268311
TI  - [The possible role of the inner mitochondrial membrane in regulating oxidative
      phosphorylation in cells in vivo].
AB  - It has been shown for the first time that the outer mitochondrial membrane has a
      low permeability for ADP and can control its diffusion into cells in vivo.
      Respiration of saponin-skinned cardiac and skeletal muscle fibers is maximally
      stimulated by millimolar concentrations of external ADP. The apparent Km values
      for ADP are equal to 297 +/- 35 and 334 +/- 54 microM, respectively. After
      complete extraction of myosin with 0.8 M KCl, which fully preserves the intact
      structure of the mitochondria, the apparent Km values for exogenously added ADP
      does not change. However, disruption of the outer mitochondrial membrane by
      osmotic shock (treatment with 40 mOsM KCl) causes a reduction of the apparent Km
      value down to 32.3 +/- 5.0 microM of ADP. The apparent Km for ADP in isolated
      heart mitochondria is 17.6 +/- 1.0 microM. It is concluded that there exists an
      intracellular factor in the cells in vivo which controls the outer mitochondrial
      membrane and notably decreases its permeability for ADP. After isolation of
      mitochondria this factor is lost. When mitochondrial creatine kinase is
      activated, weak intracellular fluxes of ADP passing through the outer
      mitochondrial membrane in the skinned fibers are amplified manifold due to the
      tight functional coupling between mitochondrial creatine kinase and the oxidative
      phosphorylation system. This coupling is considered to be the central mechanism
      in the control of cell respiration.

PMID- 8268312
TI  - [The effect of bovine serum albumin conjugates with polyalkylene oxides on the
      respiration of heart mitochondria].
AB  - The effect of polyalkylene oxides and pluronics (block copolymers of polyethylene
      oxide and polypropylene oxide) and their conjugates with bovine serum albumin
      (BSA) on respiration and oxidative phosphorylation in rat heart mitochondria has
      been studied. The pluronics and their conjugates with BSA stimulate state 4
      respiration in mitochondria, inhibit state 3 respiration and 2,4-dinitrophenol
      uncoupled state respiration, decrease the respiratory control, ADP/O ratio values
      and display weak uncoupling properties. The pluronics inhibit respiration and
      oxidative phosphorylation more effectively than their conjugates with BSA. The
      effect of the conjugate on the mitochondrial membrane is reversible, in contrast
      with that of the pluronics. The compounds under study act preferentially on the
      NADH-dehydrogenase complex of the respiratory chain. Inhibition of respiration in
      thymocytes by these compounds confirms their ability to penetrate into the cell
      membrane. The dependence of membranotropic properties of polyalkylene oxides and
      their conjugates with the protein on their structure is discussed.

PMID- 8268313
TI  - [Interrelationship of microsomal and mitochondrial systems for hydroxylating
      steroids from cattle adrenal cortex: effect of highly-purified components of the
      mitochondrial monoxygenase system on hydroxylation of steroids by microsomes].
AB  - The possibility of functioning of microsomal steroid hydroxylases in the adrenal
      cortex in the presence of the electron-transporting proteins in mitochondrial
      monooxygenase systems has been studied. It was found that adrenodoxin reductase
      stimulates both the 21- and 17 alpha-steroid hydroxylation activities in
      microsomes of the adrenal cortex with the same efficiency as does NADPH-dependent
      cytochrome P-450 reductase. Using cytochrome b5 and its specific antibody, an
      attempt has been made to investigate possible mechanisms of the stimulating
      effect of adrenodoxin reductase.

PMID- 8268314
TI  - [Rotenone-sensitive oxidation of NADH and F0F1-ATPase activity in a homogenate of
      rat skeletal muscles during thermal adaptation].
AB  - A method has been developed for measuring the rates of rotenone-sensitive
      oxidation of NADH and oligomycin-sensitive hydrolysis of ATP in rat skeletal
      muscle homogenates. The method is based on the use of alamethicin which increases
      the permeability of the inner mitochondrial membrane for NADH and ATP. It has
      been shown that prolonged cold adaptation of rats (4 weeks, 4 degrees) does not
      change the activity of rotenone-sensitive NADH-oxidase in rat skeletal muscle
      homogenates which is equal to 12.4 +/- 4.4 nmol NADH/min/mg protein, but
      increases threefold that of F0F1-ATPase--from 31.8 +/- 7.4 up to 93.1 +/- 14.3
      nmol P(i)/min/mg protein. It is suggested that prolonged cold adaptation induces
      structural-and-functional changes in the H(+)-ATP-synthetase complex of skeletal
      muscle mitochondria.

PMID- 8268315
TI  - [The effect of steroids on binding of transcortin with human
      syncytiotrophoblasts].
AB  - The effects of steroids on specific binding of transcortin (corticosteroid
      binding globulin, CBG) variants (nCBG and vCBG) from pregnant women sera to the
      microvesicular membrane fraction derived from placental syncytiotrophoblast brush
      border have been studied. It was shown that native CBG variants stripped of
      steroids lose their ability to interact with specific membrane sites. Specific
      binding of CBG variants was found to increase in parallel with an increasing per
      cent content of glycoproteins associated with cortisol, reaching a maximum at
      cortisol concentrations of 5.10(-8)-5.10(-7) M which is saturating for the
      complex formation. Specific binding sites in the syncytiotrophoblast membrane do
      not differentiate between the nCBG complexed to cortisol, corticosterone,
      progesterone or testosterone but show a selectivity towards the vCBG-cortisol
      complex.

PMID- 8268316
TI  - [Concentration-functional interrelationships in the human alternative complement
      activation pathway].
AB  - The dependence of the rate of human complement mediated lysis of rabbit
      erythrocytes on concentrations of factors B and D of the alternative pathway is
      characterized by saturation kinetics. At low B and D concentrations no lysis
      occurs until certain "threshold" concentrations of the respective factor are
      reached. The type of dependence of the hemolysis rates on the C3 concentration is
      wavelike, i.e., at definite C3 concentrations the erythrocyte lysis is inhibited.
      It has been supposed that C3 not only mediates the complement-dependent hemolysis
      but also plays a prominent role in the self-regulation of this process.

PMID- 8268317
TI  - [Amides of ganglioside GD3].
AB  - Analysis of natural ganglioside lactones usually employs NH3 treatment. In the
      present paper it has been shown that the GD3 dilactone forms with ammonia three
      rather than one GD3 amides--a GD3 diamide and two GD3 monoamides. The structure
      of these amides is discussed.

PMID- 8268318
TI  - [Hydrolysis of DNA-duplexes, containing 5-fluorodeoxycytidine by restriction
      endonucleases].
AB  - Cleavage by restriction endonucleases MvaI kappa EcoRII of DNA duplexes, in which
      the internal deoxycytidine in one of the strands of the recognition site is
      substituted for 5-fluorodeoxycytidine, has been studied. It has been found that
      the modified strands of these duplexes are scissed by endonuclease MvaI with a
      greater efficiency than the intact ones. Endonuclease EcoRII does not practically
      cleave such substrate analogs. The UV absorbance spectra of 5-fluorodeoxycytidine
      and the 14-member oligodeoxyribonucleotide with modification in the middle of the
      strand have been measured. A hypothesis has been put forward about the structural
      features of 5-fluorodeoxycytidine-containing DNA duplexes.

PMID- 8268319
TI  - [Mitochondrial proteolipids].
AB  - A convenient procedure is proposed for extracting mitochondrial proteolipids
      using a single phase mixture chloroform-methanol-water (1:2:0.8 v/v) with
      subsequent separation of the phases. The proteolipids were concentrated at the
      interface between the phases and thus purified from the bulk of the
      phospholipids. It was found that the mitochondrial proteolipids represent stable
      complexes of phospholipids with some low molecular weight proteins (M(r) = 7-18
      kDa). The latter are destroyed at acid pH values. The phospholipid/protein ratio
      was found to be equal to 6 (assuming the molecular masses of the proteins and
      phospholipids to be equal to 10 and 0.8 kDa, respectively). The phospholipid
      composition of the tightly bound proteolipids thus obtained did not differ from
      that of the mitochondrial phospholipids. Using 31P-NMR, nonbilayer structures
      were found to arise from proteolipid reconstitution into multibilayer liposomes.

PMID- 8268320
TI  - [Crystallization of three multiple forms of transketolase from baker's yeast].
AB  - Three forms of baker's yeast transketolase have been revealed. These forms
      differed in thermal stability and elution profiles during chromatography on a
      phosphocellulose column and migrated with identical rates during electrophoresis
      in the presence of sodium dodecyl sulfate. The same forms in yeast, pig and rat
      liver and in different organs and tissues of the rabbit were found to be similar
      in their thermal stability and chromatographic properties. The relative amounts
      of the forms appeared to depend on the physiological state of the organism.
      Crystals of the three pure forms were grown using ammonium sulfate as the
      precipitating agent. These crystals differed morphologically and by stability
      upon storage. The possibility of interconversion of the transketolase forms is
      discussed.

PMID- 8268321
TI  - Detection of DNA in ancient skeletal remains using DNA flow cytometry.
AB  - Cortical bone samples were removed from individual burials from Tomb Dk31 in the
      Dakhleh Oasis, Egypt. The tissue was disaggregated, stained with the DNA specific
      fluorescent dye DAPI and analyzed using the flow cytometer. DNA flow cytometry
      measures the cellular DNA content and this is correlated with modal chromosome
      content. When DNA is present in skeletal remains further investigations such as
      extracting, amplifying and sequencing may then be carried out. The method offers
      a relatively rapid and inexpensive means of pinpointing samples of skeletal DNA
      that can be further analyzed.

PMID- 8268322
TI  - Immunohistochemistry on resin sections: a comparison of resin embedding
      techniques for small mucosal biopsies.
AB  - We have modified resin embedding methods to provide optimal information from
      endoscopic biopsies. Mucosal biopsies were fixed either in buffered formalin and
      processed for embedding in Araldite or in acetone containing protease inhibitors
      and embedded in glycol methacrylate (GMA). GMA embedding generated an
      immunophenotypic profile similar to that obtained in frozen sections while
      yielding far superior morphology and greater numbers of sections from small
      biopsies. The phenotypic markers included those for T cells, macrophages, mast
      cells, eosinophils and neutrophils. We have also demonstrated collagens, cell
      adhesion molecules and integrin molecules. Sections of similar quality were
      obtained with Araldite but the repertoire of antibodies was restricted to those
      which can be applied to formalin fixed, paraffin embedded tissues. We suggest
      that for optimal results, small biopsies to be subjected to immunochemistry are
      fixed in acetone at -20 C with the inclusion of protease inhibitors and embedded
      in GUIA with careful temperature control.

PMID- 8268323
TI  - Histological techniques to improve testing of pulpal response of teeth to filling
      material.
AB  - Two fixation fluids, two fixation techniques and two embedding methods were
      investigated for their effects on the quality of sections of teeth for pulpal
      response to filling materials to improve evaluation of pulpal responses. Sections
      from 32 baboon teeth were prepared, half with experimental cavities and half
      without, using either 10% formaldehyde or 4% glutaraldehyde, longitudinal tooth
      splitting or removal of the tooth apex, and paraffin or K plast resin embedding;
      decalcification in a formic acid mixture was a constant throughout. Histometric
      analysis showed that paraffin embedding produced less shrinkage than the K Plast
      resin embedding although the difference was not statistically significant. Six
      parameters of separation at the pulp:dentine interface were studied: embedding,
      fixative, presence or absence of a cavity, cutting technique and individual
      animal tooth type. Statistical investigation revealed that fixative, cutting
      technique, and fixative and cutting technique combined had significant influences
      on the separation artifact. Of the combinations tested the choice of embedding
      method depends on which of the two artifacts, shrinkage or separation, is more
      adverse in the opinion of the investigator. Four percent glutaraldehyde together
      with the longitudinal split technique of fixation, processed by either K Plast
      resin embedding or paraffin embedding produced satisfactory pulpal sections.

PMID- 8268324
TI  - Immunocytochemical detection of bromodeoxyuridine in tissues of the toad Bufo
      arenarum Hensel.
AB  - We present a modified protocol for the immunocytochemical identification of 5
      bromo-2'-deoxyuridine (BrdU) as an indicator of cell replication in different
      tissues of the toad, Bufo arenarum Hensel. Animals were sacrificed 60 min after
      BrdU (5 mg/100 g body weight) was injected into the dorsal lymph sac. The tissues
      were fixed in Carnoy's fluid and stained by the immunoperoxidase method using an
      anti-BrdU monoclonal antibody. This protocol can be used safely for the study of
      cell replication in toads and other Anura amphibia.

PMID- 8268325
TI  - Orientation of small specimens for cryosectioning.
AB  - A simple technique is introduced to achieve symmetrically oriented frozen
      sections of small specimens such as young fish or frog larvae. Small samples are
      especially difficult to orient if they are already frozen to the chuck in a
      freezing microtome. Orientation of the sample in a mold filled with embedding
      medium prior to freezing permits sectioning as well as easy labeling and storage
      of the specimens. The use of a stereo microscope during orientation is optional.

PMID- 8268326
TI  - The pathogenesis of Tourette's syndrome: epigenetic factors active in early CNS
      development.

PMID- 8268327
TI  - Autonomic dysfunction in patients with dementia of the Alzheimer type.
AB  - Abnormalities of the noradrenergic system have been documented in the central
      nervous system of patients with dementia of the Alzheimer's type (DAT). To
      evaluate the autonomic sympathetic system in DAT, we measured lying and standing
      blood pressure (BP), pulse, and plasma epinephrine (E) and norepinephrine (NE) in
      60 DAT patients (mean age +/- SD = 65 +/- 8 years), and 20 normal elderly
      controls. DAT patients had normal baseline findings (BP, pulse, NE, and E). Upon
      standing, plasma NE and E significantly increased in both DAT patients and
      controls, without group differences. However, the systolic BP response to
      standing was reduced in DAT patients compared with the normal controls (repeated
      measures ANOVA, p < 0.01). This impaired response of the systolic BP on standing
      was particularly evident in DAT patients with symptoms of depression. Severely
      impaired DAT patients did not differ in E, NE, BP, pulse, or in orthostatic
      changes from mild-to-moderately impaired patients. These results suggest that the
      sympathetic response to the stress of standing is functionally impaired in DAT.
      This deficit was especially evident when DAT was accompanied by depression,
      consistent with prior studies in non-demented depressed patients.

PMID- 8268328
TI  - Dopamine-beta-hydroxylase in behaviorally disturbed youth. Relationship between
      teacher and parent ratings.
AB  - A series of neurotransmitters, metabolites, and enzymes considered relevant to
      emotional and behavioral disorders was studied in blood samples obtained from
      boys admitted to a residential setting because of disruptive or unmanageable
      behavior in their home environments. The youth were categorized into mainly
      prepubertal (under 12.0 years) and pubertal/post pubertal (12.0 years and over)
      groups. Behavior ratings of the younger group completed by parents revealed
      significant inverse correlations between several behavioral factors and dopamine
      beta-hydroxylase (DBH) activity levels, notably in the aggressive behavior and
      antisocial domains. Teacher ratings completed after about 1 month of living in
      the residential setting also showed numerous significant, but positive,
      correlations between several behavior factors and DBH activity levels.
      Furthermore, teacher and parent ratings themselves often were significantly and
      inversely correlated. The findings related to DBH activity levels were strongest
      in the younger group of boys. The results are discussed in terms of the
      possibility that low DBH activity in boys reflects a vulnerability towards
      behavioral disorder, which in certain environments becomes manifested by conduct
      problems and antisocial behavior.

PMID- 8268329
TI  - Event-related potential indices of semantic processing in schizophrenia.
AB  - Event-related potentials (ERPs) were recorded while schizophrenic patients and
      healthy controls read congruous and incongruous sentences in anticipation of a
      memory test. The schizophrenic group performed more poorly in both recognition
      memory and cued recall tests. The two groups did not differ in the amplitude of
      the N400 component of the ERP but the difference between the ERPs to congruous
      and incongruous sentences persisted longer in the schizophrenic sample. The
      schizophrenic sample also showed reduced parietal positivity and a reduced effect
      of congruity on the late positive component that follows N400. Within the
      schizophrenic sample, measures of attentional impairment and positive thought
      disorder were correlated with mean amplitude of both the N400 and the subsequent
      positivity. The results imply that the structure and spread of activation within
      semantic memory is not impaired in schizophrenia. Rather, impairments appear to
      lie in processes required to integrate activated information with the current
      context.

PMID- 8268330
TI  - Distribution of a novel mutation in the first exon of the human dopamine D4
      receptor gene in psychotic patients.
AB  - Disturbances in dopaminergic transmission have been implicated in the etiology of
      psychotic disorders. Interindividual differences in deoxyribonucleic acid (DNA)
      sequences coding for dopamine receptor proteins might contribute to the genetic
      background of these diseases. We have identified a variation in exon 1 of the
      dopamine D4 receptor (DRD4) gene, which is characterized by a polymorphic 12 base
      pair (bp) repeat. This repeat codes for a sequence of four amino acids in the
      extracellular N-terminal part of the receptor, which borders the first putative
      transmembrane domain. The 12bp repeat occurs as a two-fold repeat in the more
      common variant (A1 allele) and is represented only once in the rarer one (A2
      allele). The frequency of this DNA polymorphism was determined in a sample of 59
      patients suffering from delusional disorder, in 79 schizophrenic patients, and in
      75 control subjects. Sixteen (27%) of the 59 patients with delusional disorder
      carried the A2 allele compared with six (8%) of the controls. The observed
      difference in genotype frequencies between patients with delusional disorder and
      controls was highly significant. There were no significant differences in
      genotype frequencies between schizophrenics and controls: Our results strongly
      suggest the involvement of genetic variation in the DRD4 gene in conferring
      susceptibility to delusional disorder.

PMID- 8268331
TI  - Parkinson's disease and anxiety: comorbidity with depression.
AB  - Parkinson's disease (PD) is frequently accompanied by symptoms of depression and
      anxiety. However, the relationship between anxiety and depression has not been
      rigorously defined in these patients. In this study, 42 patients with PD and 21
      matched medical controls were evaluated using DSM-III-R criteria and a variety of
      psychiatric rating scales. Twelve (29%) PD patients but only one medical control
      had a formal anxiety disorder diagnosis. Of the 12 patients with PD who had an
      anxiety disorder diagnosis, 11 (92%) had a comorbid depressive disorder
      diagnosis. Of the 18 patients with a depressive disorder, 12 (67%) also had an
      anxiety disorder diagnosis. Furthermore, a stepwise regression analysis found
      that the depression measure explained 44% of the variance in anxiety measures
      whereas neither the severity of illness variables nor the levodopa dose
      contributed significantly to the variance. This study suggests that the excess
      anxiety found in PD patients is unlikely to be primarily a psychologic reaction
      to the illness or a side effect of levodopa treatment. Rather, we suggest that
      anxiety and depression are related manifestations of the underlying neurochemical
      changes of PD itself.

PMID- 8268332
TI  - Prediction of the antidepressant response to total sleep deprivation of depressed
      patients: longitudinal versus single day assessment of diurnal mood variation.
AB  - The relationship between diurnal variation of mood and the clinical response to
      total sleep deprivation (TSD) was investigated in 43 depressed patients. The
      question asked was whether the propensity to produce diurnal variations of mood
      or the actual mood course on the day before TSD determines the clinical response
      to TSD. Patients rated their mood three times daily during an experimental period
      of 56 days. The frequency as well as the amplitude of daily mood changes were
      assessed during this period. For each patient six TSDs were scheduled: two after
      days with a positive mood course, two after a negative mood course, and two after
      days without a diurnal change of mood. This strategy allowed comparisons of TSD
      responses within patients. Moreover, longitudinally and retrospectively assessed
      diurnal variation were compared with each other. It was found that patients vary
      largely in the occurrence of diurnal variations of mood. The propensity to
      produce diurnal variations either in terms of frequency or amplitude was
      positively correlated with the response to TSD. Within patients no differences
      were found in responses to TSDs applied after days with diurnal variations
      (positive or negative) or without diurnal variations. A second aim was to get
      more insight into the mechanism relating diurnal variations of mood and the TSD
      response. Therefore, the interrelatedness of various measures of diurnal
      variations, such as amplitudes and frequencies of positive or negative diurnal
      mood changes, was studied, as well as the relationships of these variables with
      TSD responses. On the basis of the strong interrelatedness it is suggested that
      they all reflect the same underlying mechanism, to be symbolized by an
      oscillator, producing positive daily fluctuations of mood.

PMID- 8268333
TI  - REM sleep parameters in the discrimination of probable Alzheimer's disease from
      old-age depression.
AB  - Thirteen dementia of the Alzheimer type (DAT) patients and fifteen old-age major
      depressive disorder (OAD) patients were investigated by polysomnography. The
      sleep was recorded during two nights after a 1 week wash-out period of
      psychotropic drugs. No statistically significant differences between the two
      groups were found concerning sleep continuity or architecture. The amount of REM
      sleep was significantly lower in DAT in comparison with OAD patients (11.7%
      verses 18.5%). Also, total REM density as well as the density of the first REM
      period were significantly lower in the DAT compared with the OAD patient group
      (15.8% verses 32.5%, 14.9% verses 38.1%, respectively). REM latency did not
      differ between both groups. Because REM latency is known from other studies to be
      shortened in depressed patients due to a cholinergic hyperactivity, the opposite
      finding, i.e., prolongation of REM latency, was expected for DAT patients. This
      assumption, however, could not be confirmed in the present study. It is concluded
      that REM density may better differentiate between DAT and OAD.

PMID- 8268334
TI  - Clozapine attenuates meta-chlorophenylpiperazine (mCPP)-induced plasma cortisol
      increases in schizophrenia.

PMID- 8268335
TI  - Evidence of increased non-adrenoceptor [3H]idazoxan binding sites in the frontal
      cortex of depressed suicide victims.

PMID- 8268336
TI  - Mutation in the beta amyloid precursor protein gene and schizophrenia.

PMID- 8268337
TI  - TRH test and suicide.

PMID- 8268338
TI  - New perspectives on bacterial meningitis.

PMID- 8268339
TI  - Photo quiz. Visceral leishmaniasis with hemophagocytic syndrome.

PMID- 8268340
TI  - Bacillary angiomatosis and bacillary peliosis in patients infected with human
      immunodeficiency virus.

PMID- 8268341
TI  - Successful treatment of antimony-resistant visceral leishmaniasis with liposomal
      amphotericin B in patients infected with human immunodeficiency virus.
AB  - We describe two cases of visceral leishmaniasis in patients infected with human
      immunodeficiency virus (HIV); both cases were resistant to antimony compounds but
      were cured with liposomal amphotericin B, with no significant toxicity. A review
      of the previous reported cases of antimony-resistant visceral leishmaniasis in
      HIV-infected patients confirmed the effectiveness of treatment with liposomal
      amphotericin B, which directly targets infected macrophages and reaches high
      levels in plasma and tissue.

PMID- 8268342
TI  - Postexposure administration of halofantrine for the prevention of malaria.
AB  - Halofantrine was administered as prophylaxis for malaria to mine workers
      returning from endemic areas of Papua New Guinea. The men were randomly assigned
      to receive 500 mg of halofantrine daily for 3 days (n = 195) or 6 days (n = 150)
      or a total dose of 1,500 mg of chloroquine over 3 days (n = 55). None of the men
      receiving halofantrine developed falciparum malaria during the subsequent 28
      days, whereas three men receiving chloroquine did develop this disease (P < .02).
      The administration of halofantrine after departure from an endemic area is one
      strategy for the prevention of falciparum malaria after short-term exposure.

PMID- 8268343
TI  - Vascular catheter-related bloodstream infection due to Acinetobacter johnsonii
      (formerly Acinetobacter calcoaceticus var. lwoffi): report of 13 cases.
AB  - Although Acinetobacter baumannii (formerly Acinetobacter calcoaceticus var.
      anitratus) is known to be an important nosocomial pathogen, the clinical impact
      of other Acinetobacter species is not fully understood. Acinetobacter johnsonii
      (formerly a subset of A. calcoaceticus var. lwoffii) is considered a commensal on
      human skin, and infections due to this organism have not been reported
      previously. During a study period of 18 months, however, 13 patients at 6
      hospitals developed catheter-related bloodstream infections caused by A.
      johnsonii. All patients had an indwelling peripheral or central venous catheter,
      and 11 patients were receiving a continuous intravenous infusion of heparin via
      the offending catheter. The clinical course of A. johnsonii bacteremia was
      usually benign. Infections responded readily to removal of the catheter, with or
      without administration of appropriate antibiotics. No insertion-site infections
      were documented. Thus A. johnsonii must be regarded as an organism that can cause
      rare cases of bloodstream infection in immunocompetent patients.

PMID- 8268344
TI  - Trichinosis: a prospective controlled study of patients ten years after acute
      infection.
AB  - The existence of chronic trichinosis as a disease entity is still a matter of
      debate. For 10 years after an outbreak of infection with Trichinella spiralis, we
      conducted a prospective controlled study of the patients involved. At the
      termination of this investigation, we undertook clinical, biochemical,
      serological, immunologic, neuroradiological, radiological, and psychological
      studies of 128 originally infected persons and 16 controls. The categories of
      symptoms most often documented in persons who had been infected were muscular
      (90%), ocular (59%), neurological (52%), and psychological (52%). Impaired muscle
      strength (56%), conjunctivitis (55%), and impaired coordination (32%) were the
      clinical manifestations most frequently encountered. Thirty-eight percent of the
      128 originally infected patients still had IgG antibodies to T. spiralis after 10
      years. Magnetic resonance imaging of the brain revealed no abnormalities. No
      calcifications of residual larvae were detected by mammography or muscle biopsy.
      The level of performance in psychometric tests was lower in the originally
      infected population than in the general population. Although patients who had had
      trichinosis differed significantly from controls in terms of a variety of
      parameters even after 10 years, we found insufficient evidence on which to
      conclude that chronic trichinosis exists as a distinct entity.

PMID- 8268345
TI  - Cytomegalovirus disease of the gastrointestinal tract in patients without AIDS.
AB  - Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract can cause
      serious disease in immunocompromised patients. Recipients of solid organ and bone
      marrow transplants, persons with malignancies, and those receiving
      immunosuppressive medications are at risk. When CMV infection of the GI tract
      causes disease, symptoms include pain, ulceration, bleeding, diarrhea, and
      perforation. All levels of the GI tract, from the oropharynx to the anus, may be
      involved. Pathological examination of involved gut typically reveals diffuse
      ulcerations and necrosis with scattered CMV inclusions, although a variety of
      other abnormalities have been described. Before the introduction of antiviral
      therapy effective against CMV, mortality was high. However, the use of
      ganciclovir or foscarnet has improved the prognosis of CMV disease of the GI
      tract dramatically. CMV infection should be included in the differential
      diagnosis of GI disease in immunocompromised patients, and the clinician should
      pursue appropriate diagnostic and therapeutic interventions aggressively.

PMID- 8268346
TI  - Diagnosis of enterovirus brain disease in hypogammaglobulinemic patients by
      polymerase chain reaction.
AB  - CSF samples taken from three patients with primary hypogammaglobulinemia and
      chronic brain disease were positive for enterovirus RNA by use of a technique
      based on the polymerase chain reaction (PCR) to amplify viral genomic sequences.
      Repeated attempts to culture viruses from the CSF from these patients were
      unsuccessful, possibly because the patients were treated regularly with
      intravenous immunoglobulin, which may have contained enough specific antibody to
      partially neutralize the viruses. Our data suggest that enteroviruses are
      responsible for diverse CNS features in patients with primary
      hypogammaglobulinemia and that for these patients the diagnosis should be pursued
      using PCR technology.

PMID- 8268347
TI  - Candidemia from a urinary tract source: microbiological aspects and clinical
      significance.
AB  - Twenty-six cases of candidemia associated with a well-defined urinary tract
      source were retrospectively identified and reviewed. Urinary tract abnormalities
      were present in 23 of 26 patients (88%), 19 (73%) of whom had urinary tract
      obstruction. Nineteen patients had undergone urinary tract procedures before the
      onset of candidemia. Episodes of candidemia were brief and low-grade in intensity
      (median duration, 1 day; median colony count, 1.5 cfu/10 mL of blood). Only eight
      patients (31%) received > or = 500 mg of amphotericin B. There were five in
      hospital deaths (19%); two of these deaths were attributed to candidiasis. No
      late complications of candidemia were documented for the surviving patients.
      Patients with urologic pathology and candiduria who undergo surgery or
      manipulation of the urinary tract are at significant risk for candidemia, and
      further studies should examine the issue of administration of prophylaxis to this
      group.

PMID- 8268348
TI  - Complications of bacteremia due to Stomatococcus mucilaginosus in neutropenic
      children.
AB  - Stomatococcus mucilaginosus, a normal inhabitant of the human oral cavity and
      upper respiratory tract, can cause fatal sepsis and meningitis in neutropenic
      patients. We identified eight cases of bacteremia due to S. mucilaginosus in
      children with cancer, of whom five developed complications despite receiving
      appropriate antibiotics. At the time cultures were positive, seven patients had
      profound neutropenia (< 100 neutrophils and band forms/mm3) and four had
      mucositis; five had central venous catheters. In two cases, there was unequivocal
      evidence of catheter-related sepsis. Bacteremia was eradicated in all patients
      within 48 hours after initiation of antibiotics. Despite prompt instigation of
      effective antibiotic therapy, the complication rates in this series were high:
      septic shock (50%), pneumonia (50%), dermatologic manifestations (38%), altered
      neurological status (25%), meningitis (13%), and adult respiratory distress
      syndrome (13%). No fatalities were attributable to S. mucilaginosus infection.
      These cases illustrate the virulence of S. mucilaginosus organisms in neutropenic
      children and suggest a substantial risk of sequelae even when adequate antibiotic
      therapy is given.

PMID- 8268349
TI  - Infections of implantable cardioverter defibrillators: approach to management.
AB  - Implantable cardioverter defibrillators are being used with increasing frequency
      for the treatment of life-threatening ventricular arrhythmias. Nevertheless, no
      guidelines exist for the management of infections of these devices. We report our
      experience with infections of these devices and review the English-language
      literature. In all cases, patients presented with local signs of generator
      infection; systemic signs of infection and bacteremia were often absent. Most
      infections are due to staphylococcus. Risk factors for the development of
      infection include placement of the device via median sternotomy during another
      cardiac surgical procedure, reoperation, and intercurrent infection at another
      site. Infections are most reliably treated with full explantation of the device
      and antibiotics. In rare cases, patients may respond to a combination of
      intravenous antibiotics and removal and replacement of only the generator.

PMID- 8268350
TI  - Endophthalmitis caused by unusual gram-negative bacilli: three case reports and
      review.
AB  - Endophthalmitis due to gram-negative bacilli has been associated with a high
      degree of vision loss. We report three cases due to the nonenteric gram-negative
      bacilli Moraxella nonliquefaciens, Haemophilus paraphrophilus, and multidrug
      resistant Haemophilus influenzae. The features of these cases are compared with
      those of other reported cases of endophthalmitis due to unusual nonenteric gram
      negative bacilli. Fifty-eight percent of patients had no vision in the affected
      eye after treatment. Early surgical intervention with vitrectomy and
      intravitreous antibiotics in addition to parenteral antibiotics should be
      included in the treatment of endophthalmitis due to gram-negative bacilli.

PMID- 8268351
TI  - Loa loa infection as a cause of migratory angioedema: report of three cases from
      the Texas Medical Center.
AB  - Loa loa is a filarial parasite that is endemic in West and Central Africa.
      Expatriates infected with L. loa commonly develop characteristic migratory
      angioedema called Calabar swellings. We describe three patients who presented
      with classical Calabar swellings for whom the diagnosis of loiasis was delayed.
      Unusual features that were present included a leukocytoclastic vasculitis seen on
      skin biopsy (case 1), a relatively short exposure to an area of endemicity (cases
      1 and 3), and a normal eosinophil count on initial evaluation (cases 2 and 3). We
      discuss the characteristic clinical manifestations of, pathological findings of,
      and therapy for loiasis. With the increased frequency of international travel, L.
      loa infection must be considered in the differential diagnosis for patients with
      migratory angioedema, urticarial vasculitis, or eosinophilia.

PMID- 8268352
TI  - Postoperative pubic osteomyelitis misdiagnosed as osteitis pubis: report of four
      cases and review.
AB  - Osteitis pubis is a painful inflammatory process resulting in bony destruction of
      the margins of the symphysis pubis. Despite six decades of speculation, the
      pathogenesis of, criteria for diagnosis of, natural history of, and optimal
      therapy for osteitis pubis remain controversial. We present four cases of
      postoperative pubic osteomyelitis that were initially thought to be typical cases
      of osteitis pubis. These cases illustrate that pubic osteomyelitis can mimic the
      principal features of osteitis pubis including characteristic pelvic pain and
      gait disturbance, symmetrical bony destruction of the symphysis pubis, absence of
      fever, a long interval between surgery and onset of symptoms, lack of response to
      antimicrobial therapy, and apparent spontaneous cure. We believe that many
      previously reported cases of osteitis pubis were actually cases of unrecognized
      pubic osteomyelitis. We advise an aggressive diagnostic approach to cases of
      apparent postoperative osteitis pubis including biopsy and needle aspiration of
      the symphysis pubis guided by computer-assisted tomography. If cultures of biopsy
      specimens are not diagnostic, open biopsy of the symphysis pubis is recommended.

PMID- 8268353
TI  - Breast abscess: coagulase-negative staphylococcus as a sole pathogen.
AB  - Breast abscesses in nonlactating women are very uncommon. Rarely have cases been
      reported in which coagulase-negative staphylococci have been isolated in pure
      culture. We describe a 67-year-old patient who had such an abscess. Specimens
      obtained by fine needle aspiration, incision and drainage, and biopsy of the
      breast mass all showed acute inflammation and many gram-positive cocci on gram
      stain and histologic examination; cultures of all specimens yielded many
      coagulase-negative staphylococci. The patient responded well to incision and
      drainage and therapy with antibiotics.

PMID- 8268354
TI  - Role of granulocyte-macrophage colony-stimulating factor as adjuvant therapy for
      fungal infection in patients with cancer.
AB  - A pilot study was conducted to evaluate the role of granulocyte-macrophage colony
      stimulating factor (GM-CSF) as adjuvant therapy for fungal infections in patients
      with cancer. GM-CSF was added to amphotericin B in the treatment of cancer
      patients with proven major-organ or disseminated fungal infection. The dose of GM
      CSF ranged from 100 to 750 micrograms/(m2.d). Of eight evaluable patients, six
      had a neutrophil response to GM-CSF. Four of these patients were completely cured
      of the fungal infection, and two had a partial response. However, a capillary
      leak syndrome developed in three patients, an adverse effect suggesting that the
      dose of GM-CSF was excessive.

PMID- 8268355
TI  - Detection of Chlamydia pneumoniae by polymerase chain reaction-enzyme immunoassay
      in an immunocompromised population.
AB  - Chlamydia pneumoniae has now been associated with pneumonia, bronchitis,
      pharyngitis, acute chest syndrome of sickle cell disease, and asthma. Because of
      the difficulty of primary isolation and tissue-culture adaptation of this
      organism, we used a previously developed polymerase chain reaction-enzyme
      immunoassay (PCR-EIA) to screen 132 culture-negative bronchoalveolar lavage (BAL)
      specimens from 108 immunocompromised patients (34% of whom were positive for
      human immunodeficiency virus) and 7 healthy volunteers. Thirteen specimens (9.8%)
      from 12 immunocompromised patients (11.1%) gave a positive result; one patient
      had two positive specimens obtained 3 days apart. No healthy volunteer had a PCR
      EIA-positive BAL specimen. Twelve (11.1%) of the immunocompromised patients also
      had diagnostic levels of antibody. Four patients had positive results in both PCR
      EIA and serological tests. Thus 20 (18.5%) of the 108 patients had laboratory
      evidence of C. pneumoniae infection. These data indicate that diagnosis of acute
      infection with C. pneumoniae can be established more rapidly and reliably by PCR
      EIA than by culture or serology, particularly among immunocompromised patients,
      in whom serological changes in response to infection are relatively undependable.
      With an infection rate of 11.1% according to PCR-EIA, C. pneumoniae should be
      considered in the evaluation and treatment of pneumonia in immunocompromised
      patients.

PMID- 8268356
TI  - Mycoplasma penetrans infection in male homosexuals with AIDS: high seroprevalence
      and association with Kaposi's sarcoma.
AB  - Antibodies to Mycoplasma penetrans were found at an unusually high frequency in
      male homosexuals with AIDS (55 of 149; 37%) and in human immunodeficiency virus
      (HIV)-infected asymptomatic homosexuals (13 of 49; 26.5%) but not in intravenous
      drug users (3 of 308; 1%) and hemophiliacs (1 of 165; 0.6%) with or without HIV-1
      infection. Thus, both M. penetrans and Kaposi's sarcoma (KS) occur primarily in
      male homosexuals and rarely in other groups of patients at high risk of AIDS.
      Among 414 HIV-1-infected patients, statistical analysis revealed those with M.
      penetrans antibody were 11.7 times more likely to develop KS. Furthermore, among
      198 HIV-infected homosexuals (149 with AIDS and 49 without AIDS), those with KS
      had M. penetrans-specific antibody at a significantly higher frequency (28 of 47;
      59.6%) than did those without KS (27 of 102 with AIDS [26.5%] as well as 13 of 49
      without AIDS [26.5%]; odds ratio = 4.1, P < .001). M. penetrans is apparently
      transmitted sexually through homosexual activity and is epidemiologically linked
      to formation of KS in homosexual men with AIDS. Parallel tests with M. genitalium
      revealed no similar link to KS in the same study sample.

PMID- 8268357
TI  - Therapy for neurocysticercosis: a reappraisal.
AB  - Accepted approaches to therapy for the different forms of neurocysticercosis are
      reviewed. Therapy must be individualized according to the level of disease
      activity and the location of the parasite. Patients with inactive disease should
      receive only symptomatic treatment. In contrast, patients with parenchymal brain
      cysts must receive a course of anticysticercal drugs. Both albendazole and
      praziquantel are useful; however, recent evidence favors the former as the drug
      of choice for this form of the disease. Albendazole (but not praziquantel) is
      also effective in the treatment of giant subarachnoid cysts; such medical
      treatment obviates surgery in some cases. Patients with ventricular cysts may
      also benefit from medical therapy; however, surgery is the current approach to
      this type of lesion, as it is to spinal cysticercosis. Although intraocular cysts
      have classically been resected by surgery, a recent study indicates that
      albendazole is equally effective. For patients with mixed forms of
      neurocysticercosis, therapeutic measures related to--but not directly targeting-
      the disease (i.e., steroid administration for brain edema or shunt placement for
      hydrocephalus) should be contemplated before therapy with anticysticercal drugs
      is instituted.

PMID- 8268358
TI  - Cryptococcal peritonitis: report of a case developing during continuous
      ambulatory peritoneal dialysis and review of the literature.
AB  - A patient developed cryptococcal peritonitis with systemic dissemination during
      continuous ambulatory peritoneal dialysis (CAPD). This case prompted a search of
      the literature for cases of cryptococcal peritonitis; 19 previously reported
      cases were identified. On the basis of their clinical characteristics, these
      cases were divided into two groups. Group 1 included 10 cases developing during
      CAPD. Treatment consisted of removal of the peritoneal dialysis catheter and
      administration of a short course of amphotericin B. Eight of the 10 cases had a
      benign course, and nine patients survived. Group 2 comprised 10 cases developing
      in patients with severe underlying illnesses, such as chronic liver disease,
      AIDS, systemic lupus erythematosus, and leukemia. Disseminated cryptococcosis was
      documented in eight of the nine patients in this group for whom relevant
      information was available. Seven patients died, some despite antifungal therapy.
      Cryptococcal disease may have protean manifestations and an insidious course.
      Accordingly, the diagnosis of cryptococcal peritonitis may well be delayed. An
      awareness of this entity may lead to earlier diagnosis and treatment and possibly
      to improved outcome.

PMID- 8268359
TI  - Infections associated with the genus Edwardsiella: the role of Edwardsiella tarda
      in human disease.
AB  - The role of the genus Edwardsiella in human illness is reviewed. Of the three
      recognized species, only Edwardsiella tarda has been demonstrated to be
      pathogenic for humans. Chief infections associated with this species include
      bacterial gastroenteritis, wound infections such as cellulitis or gas gangrene
      associated with trauma to mucosal surfaces, and systemic disease such as
      septicemia, meningitis, cholecystitis, and osteomyelitis. Risk factors that are
      associated with E. tarda infections include exposure to aquatic environments or
      exotic animals (e.g., reptiles or amphibia), preexisting liver disease,
      conditions leading to iron overload, and dietary habits (e.g., raw fish
      ingestion). Although studies indicate that this bacterium is susceptible to most
      commonly prescribed antibiotics, fatal gastrointestinal and extraintestinal
      infections have been described.

PMID- 8268360
TI  - Immune-based therapeutics: scientific rationale and the promising approaches to
      the treatment of the human immunodeficiency virus-infected individual.
AB  - The primary approach to therapy for infection with human immunodeficiency virus
      (HIV) continues to be centered around antiretroviral agents that have conferred
      significant clinical benefits. The considerable degree of immunologic dysfunction
      in HIV infection, however, has led to intense interest in methods of immune
      stimulation and reconstitution. Immunomodulatory intervention in HIV infection is
      highly controversial. Over the years a number of immunomodulatory agents--many
      with only a poor rationale for their clinical use--have been evaluated. In this
      review we concentrate on immunomodulatory approaches that are currently being
      investigated. We group these interventions, reviewing the rationale and clinical
      data for each category: passive immunity (administration of immunoglobulins and
      use of apheresis), thymic hormone treatment, cytokine treatment (administration
      of interleukins, tumor necrosis factor, and interferons), adoptive cellular
      immunity, and therapeutic vaccination. At present, the only interventions
      supported by data from well-controlled studies are the parenteral administration
      of interferon alpha to patients with HIV-associated Kaposi's sarcoma and the
      administration of pooled immunoglobulin (to decrease the rate of bacterial
      infections) to children who cannot take trimethoprim-sulfamethoxazole. However,
      several other approaches under development show promise in reversing some of the
      immune deficits of HIV infection. Clinical evaluation of these approaches should
      yield valuable insights into the immunopathogenesis of HIV infection, and these
      insights should facilitate the formulation of new modalities of treatment.

PMID- 8268361
TI  - Rothia dentocariosa endocarditis complicated by perivalvular abscess.
AB  - A 35-year-old man with a history of intravenous drug use developed endocarditis
      due to Rothia dentocariosa that was complicated by a perivalvular abscess.
      Despite combined medical and surgical treatment, abscess formation progressed
      following aortic valve replacement, and the patient died during a second
      operative procedure. This is the sixth case of Rothia dentocariosa endocarditis
      reported in the English-language literature, and to our knowledge, the only case
      in which a perivalvular abscess has been documented.

PMID- 8268362
TI  - Cutaneous cryptococcosis in a patient with cutaneous T cell lymphoma receiving
      therapy with photopheresis and methotrexate.
AB  - Photopheresis is being used with increasing frequency as therapy for patients
      with neoplastic and dermatologic diseases and is being evaluated as therapy for
      patients with AIDS. We describe a patient with advanced cutaneous T cell lymphoma
      who developed pulmonary and cutaneous cryptococcosis after receiving therapy with
      photopheresis and biweekly methotrexate. We consider the potential roles of
      cutaneous T cell lymphoma, methotrexate, and photopheresis as predisposing
      factors in the development of serious cryptococcal infections.

PMID- 8268363
TI  - Short-term treatment of traveler's diarrhea with norfloxacin: a double-blind,
      placebo-controlled study during two seasons.
AB  - Clinical efficacy of norfloxacin for treatment of traveler's diarrhea in 106
      Finnish tourists vacationing in Morocco was evaluated during two different
      seasons. When the criteria for diagnosis of traveler's diarrhea were fulfilled,
      norfloxacin (400 mg) or a placebo was given orally, twice daily for 3 days. All
      symptoms and signs subsided sooner in the norfloxacin group. The clearest
      difference was observed in the duration of diarrhea: 1.2 days in the norfloxacin
      group vs. 3.3 days in the placebo group (P < .001). The duration of diarrhea due
      to particular species was as follows for the two groups: in cases due to
      Salmonella enterica, 1.1 vs 4.1 days (P < .01); in cases due to Campylobacter
      jejuni, 1.8 vs. 5.0 days (P < .01); and in cases due to enterotoxigenic
      Escherichia coli, 1.0 day vs. 3.1 days (P < .01). The rate of full recovery
      during administration of norfloxacin or a placebo was also greater among the
      norfloxacin recipients: 84% vs. 47% (P < .001). No significant adverse effects
      were reported. Norfloxacin proved to be safe and effective in therapy for
      traveler's diarrhea.

PMID- 8268364
TI  - Persistent bacteremia with Erysipelothrix rhusiopathiae in a hospitalized
      patient.
AB  - A patient with a history of alcohol abuse and pancreatitis presented with a
      pleural effusion resulting from a fistula between the pancreatic duct and left
      pleural space. Two weeks into her hospitalization, fever and persistent
      bloodstream infection with Erysipelothrix rhusiopathiae and Candida albicans
      developed. The patient had no history of exposure to animals. To our knowledge
      this is the first report of an E. rhusiopathiae infection presenting during
      hospitalization. This case suggests the possibility of a carrier state of
      infection and illustrates that a high index of suspicion is necessary for
      identification of unusual pathogens in hospitalized patients.

PMID- 8268365
TI  - Meningoencephalitis and polyradiculoneuritis in adults: don't forget rubella.
AB  - We describe a severe case of meningoencephalitis and polyradiculoneuritis that
      occurred following rubella in an otherwise healthy 19-year-old man. The diagnosis
      was made serologically. To our knowledge this is the first reported case of
      extensive neurological involvement in an adult with rubella.

PMID- 8268366
TI  - European guidelines for anti-infective drug products. Introduction.

PMID- 8268367
TI  - Evaluation of new anti-infective drugs for the treatment of vascular access
      device-associated bacteremia and fungemia. The European Working Party of the
      European Society of Clinical Microbiology and Infectious Diseases.
AB  - For clinical trials of anti-infective drugs for the treatment of vascular access
      device-related bloodstream infections, patients should be identified and enrolled
      on the basis of current standards for the clinical diagnosis of such infections.
      To ensure comparability of patients, only those infected with staphylococci and
      Candida species should be included. A prospective, randomized, double-blind
      design is recommended. Future protocols may include abbreviated courses of
      therapy, treatment with combinations of drugs, or a progression from parenteral
      to oral therapy. Clinical response is judged as cure, failure, or indeterminate
      response; there is no "improved" category. Microbiological response is
      categorized as eradication, persistence, or relapse and is of paramount
      importance. Several months of follow-up may be necessary for the detection of
      late relapses or metastatic infections. This guideline does not apply to studies
      of bacteremia or fungemia secondary to non-device-related, organ-based primary
      infections (e.g., pneumonia, urinary tract infection), which should be assessed
      in relation to the primary disorder.

PMID- 8268368
TI  - Evaluation of new anti-infective drugs for the treatment of infection with human
      immunodeficiency virus. The European Working Party of the European Society of
      Clinical Microbiology and Infectious Diseases.
AB  - This guideline describes the preclinical documentation required for a new drug
      active against human immunodeficiency virus (HIV) and offers suggestions
      regarding the design and implementation of phase 1, 2, and 3 clinical trials.
      Drugs with a low level of potential toxicity, especially those that are not
      nucleoside analogues, should be evaluated in healthy individuals who are not
      infected with HIV before trials in HIV-infected patients commence. The guideline
      also discusses possible clinical and laboratory end points for efficacy and
      emphasizes the need for careful validation of all laboratory end points used. The
      approach of the guideline is deliberately general: more specific recommendations
      would soon become outdated in this field, which is characterized by extremely
      rapid developments.

PMID- 8268369
TI  - Falciparum malaria during pregnancy: resolution without therapy.

PMID- 8268370
TI  - Bladder irrigation with amphotericin B for treatment of patients with candiduria.

PMID- 8268371
TI  - Should all catheterized patients with candiduria be treated?

PMID- 8268372
TI  - Spontaneous bacterial peritonitis due to Corynebacterium xerosis.

PMID- 8268373
TI  - Campylobacter species: identification and resistance to quinolones.

PMID- 8268374
TI  - Listerial brain abscess in a patient with chronic lymphocytic leukemia treated
      with fludarabine.

PMID- 8268375
TI  - Amphotericin B-induced malignant hypertension.

PMID- 8268376
TI  - Septicemia due to beta-lactamase-positive Kingella kingae.

PMID- 8268377
TI  - Fulminant community-acquired Acinetobacter pneumonia in a healthy woman.

PMID- 8268378
TI  - Chlamydia psittaci as a cause of lethal bacterial endocarditis.

PMID- 8268379
TI  - Evaluation of hollow and full stems implanted in the rabbit tibia: preliminary
      results.
AB  - Full and hollow stems were implanted in the right and left tibiae of five rabbits
      to study the effects of the implant shape on revascularization and remodelling of
      the bone after 6 months. No significant difference of periosteal and endosteal
      circumference was observed when the left and right tibiae of each group were
      compared. Medullary area was, not surprisingly, significantly smaller in the full
      stem implanted tibiae. The cortical bone area result was significantly higher in
      the hollow stem group. In hollow stems, vessels were present both inside and
      outside the implant with connections through the holes of the implant. The
      observed differences of cortical bone area can be explained in terms of increased
      vascular spaces inside the cortical bone of full stem implanted tibiae. This
      supports the hypothesis that hollow implants provide more space for medullary
      revascularization and are consequently capable of inducing less endosteal
      remodelling. Cementless prostheses rely for mechanical fixation on a large
      interface of the implant with bone. Two factors, i.e. revascularization of the
      medullary canal and stiffness of the stem, can have a relevant effect on the
      quality of interface. This non-weight-bearing model suggests the relevance of
      vascular factors.

PMID- 8268380
TI  - Development and functionality of isoelastic dental implants of titanium alloys.
AB  - Two types of isoelastic endosseous dental implants were produced and their
      functionality was tested. One type consisted of a porous sintered TiTa30 alloy,
      the other had a special surface structure consisting of titanium wire loops.
      Their mechanical properties were optimized by the production parameter (sintering
      and diffusion bonding, respectively). The functionality was tested after
      insertion into an artificial jaw which had properties corresponding to the
      natural mandibular. The elastic properties of both implants were similar to the
      properties of the bone. In addition the implants have a safe anchorage bone
      ingrowth. In animal experiments using the implant with surface loops it was
      observed that the bone entered the loops and even extremely small surface
      cavities in the wire loops.

PMID- 8268381
TI  - Surface analysis of titanium implants.
AB  - Medical grade titanium samples were examined using X-ray photoelectron
      spectroscopy before and after immersion in various proteins. Additionally, an
      implant removed from a patient following clinical failure was examined using
      scanning ion and electron microscopy. The surface of the as-received samples was
      found to be mainly TiO2, with contaminants of H2O/OH-, calcium and nitrogen which
      remained after autoclaving. The immersed proteins adhered to the titanium
      surface, possibly via a Ca-O link. The failed clinical sample was found to be
      partially fibrously encapsulated with evidence of calcification. Small amounts of
      TiOOH were detected at the fibrous periphery, supporting the theory of Tengvall
      and co-workers that in vivo titanium implants are covered in a gel of this
      material.

PMID- 8268382
TI  - X-ray diffraction of newly formed bone close to alumina- or hydroxyapatite-coated
      femoral stem.
AB  - The study was focused on the bone tissue response to two types of ceramic coating
      [alumina and hydroxyapatite (HA)] obtained with a plasma-spray technique. The HA
      coating was performed on titanium stems, while the alumina coating was on
      chromium-cobalt-molybdenum stems. The investigation was carried out by means of
      micro-area X-ray diffractometric analyses and microdiffractometric analyses at
      the bone-implant interface. Moreover, the coating before and after implantation
      was analysed by means of the conventional powder X-ray diffractometric technique.
      This study demonstrated that 1 yr after implantation in animals the newly formed
      bone adjacent to the HA-coated hip prosthesis stems was mineralized as much as
      the pre-existing bone, while 24-64 months after surgery in humans the newly
      formed bone close to the alumina-coated hip prosthesis stems showed a lamellar
      and Haversian structure strongly demineralized, probably due to the release of
      aluminum ions from the alumina covering. The authors conclude that the X-ray
      diffraction allows the evaluation of the structural modifications of the ceramic
      coating, the bone formation rate close to the coating and the chemical nature of
      the particles released from the coating.

PMID- 8268383
TI  - Biocompatibility of glass ionomer cements.
AB  - Glass ionomer cements (GICs) are widely used in the dental field and are
      increasingly being considered as materials with potentially good osteogenic
      properties. This paper details a comprehensive biocompatibility evaluation of a
      number of GICs. These include conventional, commercially available materials,
      novel formulations and a new light cured material. The experimental programme
      entailed in vitro cell culture studies using direct contact and extraction tests
      and an in vitro rat model in which the GICs were in intimate contact with bone
      for periods up to 8 wk. The results demonstrate clear differences between the
      materials and in particular highlight the poor cellular response to the light
      cured material. Methylthiazolyldiphenyl tetrazolium assay demonstrates
      stimulation of cell growth by some GIC formulations and indicates that cytotoxic
      leachable agents can be removed from others. The results obtained following
      implantation into bone are comprehensively presented using photomicrographs. New
      bone formation with time is demonstrated with a number of formulations.

PMID- 8268384
TI  - Osteoconductive properties of methylpyrrolidinone chitosan in an animal model.
AB  - Bone defects were surgically produced in the tibiae of rabbits and medicated with
      freeze-dried methylpyrrolidinone chitosan. Histological observations 60 d after
      surgery showed a considerable presence of neoformed bone tissue, as opposed to
      controls, originating from the pre-existing bone as well as from the periosteum.
      The cationic nature and the chelating ability of the methylpyrrolidinone chitosan
      apparently favoured mineralization. Endosteal-periosteal and bone marrow
      osteoblast-like precursors, stimulated by growth factors entrapped in the
      coagulum-polysaccharide mixture, gave rise to intramembranous bone formation. The
      ultrastructural examination evidenced that bone osteoid was followed by
      mineralization of the tissue.

PMID- 8268385
TI  - Relation between the physicochemical characteristics of collagen and its
      interactions with chitosan: I.
AB  - The interaction between bovine atelocollagen and a high molecular weight fully
      deacetylated chitosan has been studied. Considering the apparent mass of an
      anionic equivalent of collagen and the results of various techniques
      (potentiometry, conductometry and IR spectroscopy), a purely electrostatic
      mechanism is demonstrated. The role of charge density and chain length of
      collagen chains is discussed, and although the interaction is weak and hindered
      by gel formation in collagen solutions, a polyanion-polycation complex is
      obtained. Circular dichroism spectroscopy experiments show an organization in the
      solid state of the complex which is quite different to those of collagen and
      chitosan.

PMID- 8268386
TI  - Chitosan matrix for oral sustained delivery of ampicillin.
AB  - Ampicillin was embedded in a chitosan matrix to develop an oral release dosage
      form. The in vitro release profile of ampicillin from chitosan beads and
      microgranules of chitosan was monitored, as a function of time, using a UV
      Spectrophotometer. The releasing studies were performed in a rotating shaker at
      100 r.p.m., containing 0.1 M HCI buffer, pH 2.0, or 0.1 M phosphate buffer, pH
      7.4, solutions, and a comparison was made between the drug loaded microbeads and
      microgranules. It seems that the amount and percentage of drug release was much
      higher in HCI solution compared with the phosphate solution, probably due to the
      gelation properties of the matrix at acid pH. The release rate of ampicillin from
      the chitosan matrix was slower for the beads as compared with the granules. From
      scanning electron microscopic studies, it appears that the drug forms a crystal
      structure within the chitosan beads, which dissolves out slowly to the
      dissolution medium through the micropores of the chitosan matrix. The results
      propose the possibility of modifying the formulation in order to obtain the
      desired controlled release of the drug for a convenient oral sustained delivery
      system.

PMID- 8268387
TI  - Water mobility and structure in poly[2-hydroxyethylmethacrylate] hydrogels by
      means of the pulsed field gradient NMR technique.
AB  - The translational mobility of water in poly[2-hydroxyethylmethacrylate] (pHEMA)
      hydrogels, cross-linked with ethyleneglycoldimethacrylate, was studied by means
      of the pulsed field gradient (PFG) nuclear magnetic resonance (NMR) technique,
      which offers the opportunity to study the molecular displacements directly under
      well-defined equilibrium conditions, resulting in a determination of the self
      diffusion coefficient. It is possible to check whether coexisting water phases
      with different mobilities (on a timescale of ca. 10 ms) are present. The
      dependence of the diffusion coefficient of water on the degree of hydration and
      the cross-linker concentration was measured. Magnetic interaction is found to
      cause cross-relaxation between the protons of water and those of the polymer
      matrix. This affects the data, rendering the evaluation by the standard equation
      invalid. An equation taking cross-relaxation into account has been derived.
      Amplitude measurements have shown that all the water in the gels contributes to
      the NMR signal. The PFG measurements have shown that the total water phase in a
      gel diffuses as one homogeneous phase, which can be characterized by a diffusion
      coefficient. The self-diffusion coefficient is strongly dependent on the degree
      of hydration of the gel; the cross-linker concentration has no measurable effect.
      The strong dependence of the diffusion of water on its concentration in the gel
      has consequences for the modelling of the swelling and drug-release dynamics of
      pHEMA and necessitates a revision of the present models describing these
      processes.

PMID- 8268388
TI  - Coated macroporous carriers with oxirane groups and their reactivity.
AB  - Macroporous carriers were prepared by coating controlled pore silicas with
      copolymers of hydroxyalkyl methacrylate and alkaline dimethacrylate activated by
      epichlorhydrin (140-1000 mumol/g epoxide group content). The relationship between
      the preparation conditions (the monomer ratio, the nature of the solvent, the
      method of activation by epichlorhydrin and the reaction temperature) was studied,
      as well as the surface characteristics responsible for the carrier's ability to
      bond (the value of the surface area before and after coating with copolymers and
      the degree of cross-linking required for the accessibility of the reactive
      groups). The coupling of various amino compounds, ammonia, aminopropanol, 1,2
      diaminoethane, 1,6-diaminohexane and, as a model enzyme, alpha chymotrypsin on to
      derivatized carriers was investigated as a function of pH, reaction time and the
      concentration of the compound bonded.

PMID- 8268389
TI  - Selective adhesion and proliferation of cells on ion-implanted polymer domains.
AB  - We have found that the adhesion and proliferation of endothelial cells can be
      drastically improved when cultivated on an ion-implanted polymer surface. When
      the surface of segmented polyurethane, where endothelial cells are not capable of
      proliferating, is modified by Ne+ or Na+ ion implantation with a fluence of 1 x
      10(15) ions/cm2 at an energy of 150 keV, cell adhesion and proliferation occurred
      selectively on the ion-implanted region irrespective of the ion species. The
      cells did not proliferate at ion fluences below 1 x 10(14) ions/cm2. Most cells
      migrated into the ion-implanted domain within 1-2 h, but some of the cells
      attached outside of the region and then slowly migrated into the region. Ion
      implantation of polystyrene, on which cells are capable of proliferating, further
      promoted cell spreading and proliferation, and increased resistance to detachment
      when the cells were exposed to trypsin.

PMID- 8268390
TI  - Synthesis and anticonvulsant activity of 1,3-dihydro-5-phenyl-2H-pyrido[3,2-e]
      1,4-diazepin-2-ones.
AB  - 1,3-Dihydro-5-phenyl-2H-pyrido[3,2-e]-1,4-diazepin-2-ones (11-13), in which the
      chlorophenyl ring of 7-chloro-1,4-benzodiazepin-2-ones is replaced by a pyridyl
      ring, were synthesized and evaluated as anticonvulsants using subcutaneous
      pentylenetetrazole (scPTZ) and maximal electroshock (MES) induced seizure
      screening tests. A methyl substituent at the N-1 and/or C-3 position of the
      diazepin-2-one ring system was not a determinant of scPTZ activity, but the 1,3
      dimethyl derivative (13) was more potent than the parent 1,3-unsubstituted
      compound (11) in the MES screen. 1,3-Dihydro-1,3-dimethyl-5-phenyl-2H-pyrido[3,2
      e]-1,4-diazepin-2- one (13) inhibited sc bicuculline and sc picrotoxin induced
      seizures, but it did not inhibit in vitro benzodiazepine binding which suggests
      it may act by a different mechanism of action. In the mouse Phase II scPTZ screen
      all compounds tested were less active than clonazepam but more active than
      valproic acid.

PMID- 8268391
TI  - Designing metalloinhibitors for delivery to peptide receptors in enzymes.
AB  - Metalloenzymes are frequently targets for the action of drugs which exert their
      effects through direct coordination to a metal receptor. The reverse of this
      principle, the simple new concept of using inhibitors containing metal ions to
      target peptide receptors in enzymes, is now described. Such "metalloinhibitors"
      have opportunities for covalent or ionic metal-enzyme interactions which can
      substantially increase the inhibitor-enzyme binding energy that usually arises
      from combined ionic, hydrogen-bonding and hydrophobic interactions. Although
      simple metal salts are known to inhibit numerous enzymes in vitro, no concerted
      attempts have yet been made to elaborate ligand environments of metals in order
      to potentiate inhibition, provide enzyme selectivity or protect against
      compromising in vivo toxicities. Regulation of the ligand microenvironment of the
      metal can produce spectacular changes in coordinating properties of and ligand
      affinities for metal ions. Strategies are now proposed for optimising inhibitor
      enzyme binding, enhancing selectivity, limiting toxicity and for efficient
      delivery of this new category of prospective drugs.

PMID- 8268392
TI  - Synthesis and benzodiazepine receptor affinity of N-(indol-3-ylglyoxylyl)
      dipeptide derivatives. Structural requirements for inverse agonist/antagonist
      receptor interactions.
AB  - Several N-(indol-3-ylglyoxylyl)dipeptide derivatives 1-12 were synthesized and
      tested for their affinity at the benzodiazepine receptor in bovine cortical
      membranes. They proved to bind with low or no affinity at the receptor site. It
      was hypothesized that this result was not due to the steric hindrance of the
      dipeptide side chain, but to the establishment of intramolecular hydrogen bonds
      involving the indole N-H and/or the glyoxylyl C = O(2). Conformational analysis
      indicated that coiled conformations, with intramolecular hydrogen bonds, were
      energetically more favoured than the staggered, completely unfolded ones.
      Therefore, the low or no affinity of these compounds should be attributed to the
      unavailability of the N-H and/or C = O(2) groups for the binding, again
      confirming that both these groups are necessary for interaction with the
      receptor.

PMID- 8268393
TI  - Conformational analysis and molecular modelling of a partial GABAA agonist and a
      glycine antagonist related to the GABAA agonist, THIP.
AB  - A series of 3-hydroxyisoxazoles (3-isoxazoles) substituted in the 5-position by
      piperidyl moieties (2-, 3-, and 4-PIOL) were studied by molecular modelling and
      computer graphics methods. Whereas 2-PIOL is pharmacologically inactive, 3-PIOL
      is a glycine antagonist and 4-PIOL a low-efficacy partial GABAA agonist. A
      conformational analysis of the isomeric PIOLs was performed on the basis of
      molecular mechanics calculations. The conformational analysis revealed a large
      degree of conformational freedom for all three compounds, especially of
      conformers having the 3-hydroxyisoxazole moiety in equatorial positions. By
      comparison of the PIOLs with the semi-rigid GABAA agonist THIP and the
      conformationally restricted glycine antagonist THAZ, the conformations relevant
      for GABAA and glycine receptor recognition were determined. For 2-PIOL a
      predicted active conformation is energetically favourable, but it exhibits
      considerable extra volume as compared to THIP, which may explain its lack of
      affinity for GABAA receptors. 3-PIOL is capable of adopting a conformation
      resembling that of THAZ. The GABAA receptor affinity of 4-PIOL may be explained
      by its ability to orientate the functional groups in space in a manner that
      allows a comparison with THIP. The low efficacy and affinity of 4-PIOL may
      reflect that not all atoms are directly involved in receptor binding. Certain
      steric requirements for binding to the GABAA receptor site have been identified
      and discussed.

PMID- 8268394
TI  - Interactive multivariate analysis of bisindolylmaleimides as potent protein
      kinase C antagonists.
AB  - The isoenzyme protein kinase C (PKC) inhibitory activity of substituted
      bisindolylmaleimides depends on the molecular weight, the total charge, and
      dipole moments. The validity of the resulting QSAR equation was investigated by
      interactive diagnostic statistics and multivariate simultaneous statistical
      inference. Molecular mechanics and dynamics can be used to study possible reasons
      of flagged observations (high-leverage points, influential data, outliers) of
      QSAR systems.

PMID- 8268395
TI  - Synthesis of the enantiomers of the bioreductively-activated cytotoxin RSU-1069
      and its prodrug RB6145 and lack of stereoselectivity in their cytotoxicity and
      radiosensitization in vitro.
AB  - The R(+)- and S(-)-enantiomers of the radiosensitizer and bioreductively
      activated cytotoxin RSU-1069 and their prodrugs have been synthesised. The parent
      drugs were evaluated as radiosensitizers and bioreductively-activated cytotoxins
      in vitro. No stereoselectivity in the activities in vitro of the two enantiomers
      was evident and both compounds were potent hypoxia-selective agents.

PMID- 8268396
TI  - Increased interleukin 6 mRNA expression by peripheral blood T cells from patients
      with IgA nephropathy.
AB  - We investigated interleukin 6 (IL-6) mRNA expression in peripheral blood T-cells
      obtained from 36 patients with IgA nephropathy (IgAN), 36 patients with other
      glomerulonephritides and 24 healthy age-matched controls. The majority of
      patients with IgAN had increased IL-6 mRNA expression by their T cells; no IL-6
      mRNA was detected in T cells obtained from patients with other
      glomerulonephritides or normal controls. A positive correlation was noted between
      the IL-6 mRNA level and quantity of protein excretion in the urine,
      histopathological findings, and renal function. However, there was no significant
      correlation between IL-6 mRNA expression and the IgA-immune complex titer, serum
      IgA level or blood pressure. mRNA levels in T cells obtained from patients with
      grade III or IV renal histopathological findings were significantly higher than
      in those with grade I or II histopathology. In addition, mRNA levels in T cells
      obtained from patients with more than 1.0 g/day proteinuria were markedly higher
      than those with less than 1.0 g/day proteinuria. We also studied the clinical
      course of 11 patients with IgAN during hospitalization. The IL-6 mRNA levels in
      these patients decreased gradually, as did proteinuria, after treatment. These
      studies suggest that abnormally regulated IL-6 mRNA expression in peripheral
      blood T cells may be associated with disease activity in IgAN.

PMID- 8268397
TI  - Immunization of BALB/c mice with a monoclonal anti-DNA antibody induces an anti
      idiotypic antibody reactive with a cell-surface DNA binding protein.
AB  - DNA binds to cell-surface proteins on human and murine leukocytes and induces
      secretion of the cytokine interleukin 6 (IL-6). Cell-surface DNA binding
      molecules have been shown to serve as target antigens for the production of
      autoantibodies in patients with systemic lupus erythematosus (SLE), and in lupus
      prone mice. Recent studies have demonstrated that a subset of anti-anti-DNA
      antibodies, isolated from patients with SLE, are idiotypically related to
      antibodies reactive with a cell-surface DNA binding molecule. We now report that
      immunization of normal mice with a murine monoclonal anti-DNA antibody induces an
      anti-idiotypic response which has reactivity with a cell-surface DNA binding
      molecule. An anti-idiotypic anti-DNA monoclonal antibody (LB17) was isolated from
      the spleen of an immunized mouse. This monoclonal antibody blocked the binding of
      DNA to murine splenocytes and mimicked the functional effect of DNA by
      stimulating the secretion of IL-6. These experiments provide further evidence for
      an idiotypic connectivity between antibodies to cell-surface DNA binding proteins
      and anti-DNA antibodies. It is hypothesized that this idiotypic system is part of
      the network of natural autoantibodies and that its perturbation may give rise to
      pathogenic antibodies.

PMID- 8268398
TI  - Effect of gangliosides in the autoimmune response induced by liposome-associated
      antigens.
AB  - A model of autoimmunity to rat male accessory glands (RAG) was recently developed
      by intraperitoneal administration of three doses of native RAG associated with
      liposomes. In this work we analysed the effects of gangliosides in the cellular
      response to RAG when they were intraperitoneally administrated prior to the
      second dose of liposome-associated RAG. Results show that the ganglioside
      treatment could modify an established DTH response. Also, gangliosides markedly
      reduced the number of Ia antigen-positive peritoneal exudated cells (PEC).
      However, they modified neither the processing of liposomes through PEC nor their
      viability. Moreover, we obtained cellular response by transferring PEC from
      immunized donors into naive receptors.

PMID- 8268399
TI  - Influence of microbial agents on the development and prevention of autoimmune
      diabetes.
AB  - For some time now, microbial agents have been implicated in the etiology of
      autoimmune diseases, including insulin dependent diabetes mellitus (IDDM). Recent
      studies, however, have revealed that exposure of genetically diabetes-susceptible
      animals to certain microbes or microbial agents at an early age prevents the
      induction and progression of disease. This suggests that microbes may act to
      modulate the immunological status or immune repertoire of an individual
      genetically programmed for IDDM away from an autoimmune response. Immunization
      with microbial agents at an early age may offer an important new direction for
      the immunotherapy of IDDM.

PMID- 8268400
TI  - What is the role of autoimmunity in AIDS?

PMID- 8268401
TI  - [Determining energy density distribution in laser irradiation fields, generated
      by the LILAB system].
AB  - Laser energy densities of less than 1 J/cm2 had no apparent effect on human
      tissues, while energy densities of more than 4 J/cm2 resulted in tissue damage.
      For non-punctiform laser applications, therefore, a laser beam distribution
      system that provides a homogeneous energy density distribution is of advantage,
      since such a system permits safe application of the laser in the effective
      therapeutic range. Conventional laser scanners for medical use have been reported
      to produce grossly inhomogeneous energy density distributions. The new LILAB
      system, which is a very fast laser beam distribution system, readily generates
      application fields of different configuration with high homogeneous energy
      density distribution. The article presents an example of a randomly selected
      application field, in which the energy densities at the edges and at the centre
      are compared.

PMID- 8268402
TI  - [Measuring plantar pressure in conventional shoes with the TEKSCAN sensory
      system].
AB  - This article describes the assessment of the TEKSCAN pressure monitoring system
      used in association with normal footwear. After allowing a warm-up period of 5-10
      minutes inside the shoe the stability of the sensor output improved as compared
      with the falsely higher pressures recorded when the warm-up period was not
      observed. The intra-person coefficient of variation of a single sensor was < 23%,
      and the intersensor variation was < 31%. However, intrasensor variation was
      reduced to 15% by appropriate prior preparation. Neither repeated use (< 6 times)
      of a sensor in a single shoe, nor the use of a single sensor in several different
      shoes had any effect on sensor function. Active deformation of the sensor
      resulted in so significant signal.

PMID- 8268403
TI  - [In vitro toxicity tests of bioceramics and bone transplants in fibroblast
      culture].
AB  - Prior to the clinical use of synthetic bone substitutes and allogenic bone
      transplants, potential toxicity resulting from various different manufacturing,
      storage, and sterilisation techniques should be excluded. In order to develop a
      reliable and reproducible in vitro model for the investigation of possible tissue
      reactions after implantation of biomaterials, we modified an established animal
      fibroblast culture technique used to test chemical agents for acute unspecific
      cytotoxicity. Subcultivation of human fibroblasts produces stable monolayer
      cultures with the aid of which, standardised, accurate and reproducible
      evaluation of toxic effects, as well as the direct visualisation of fibroblast
      ingrowth into porous implant material, is possible. Gamma-irradiated synthetic
      implants and bovine hydroxyapatite failed to show any substantial cytotoxicity.
      In contrast, ethylene oxide sterilised implant material, as well as fresh
      untreated trabecular bone showed a significant toxic effect in comparison with
      cryopreserved and autoclaved trabecular bone.

PMID- 8268404
TI  - [Stress measurements with an instrumented internal spinal fixator].
AB  - Little is known about the loads acting on internal spinal fixation devices. The
      effective forces and moments associated with different external loads have now
      been measured using instrumented implants. Measurements were obtained in intact
      cadaver spines and following vertebrectomy. The influence of the implant itself
      on the distribution of the loads was also investigated. It was found that the
      implants are not loaded symmetrically. Following vertebrectomy, the forces acting
      on the fixation device are significantly higher than in the case of an intact
      spine.

PMID- 8268405
TI  - Studies of DNA dumbbells. IV. Preparation and melting of a DNA dumbbell with the
      16 base-pair sequence 5'G-T-A-T-C-C-C-T-C-T-G-G-A-T-A-C3' linked on the ends by
      dodecyl chains.
AB  - The preparation and melting of a 16 base-pair duplex DNA linked on both ends by
      C12H24 (dodecyl) chains is described. Absorbance vs temperature curves (optical
      melting curves) were measured for the dodecyl-linked molecule and the same duplex
      molecule linked on the ends instead by T4 loops. Optical melting curves of both
      molecules were measured in 25, 55, and 85 mM Na+ and revealed, regardless of
      [Na+], the duplex linked by dodecyl loops is more stable by at least 6 degrees C
      than the same duplex linked by T4 loops. Experimental curves in each salt
      environment were analyzed in terms of the two-state and multistate theoretical
      models. In the two-state, or van't Hoff analysis, the melting transition is
      assumed to occur in an all-or-none manner. Thus, the only possible states
      accessible to the molecule throughout the melting transition are the completely
      intact duplex and the completely melted duplex or minicircle. In the multistate
      analysis no assumptions regarding the melting transition are required and the
      statistical occurrence of every possible partially melted state of the duplex is
      explicitly considered. Results of the analysis revealed the melting transitions
      of both the dodecyl-linked molecule and the dumbbell with T4 end loops are
      essentially two state in 25 and 55 mM Na+. In contrast, significant deviations
      from two-state behavior were observed in 85 mM Na+. From our previously published
      melting data of DNA dumbbells with Tn end loops where n = 2, 3, 4, 6, 8, 10, 14
      [T. M. Paner, M. Amaratunga, and A. S. Benight, (1992) Biopolymers, Vol. 32, pp.
      881-892] and the dumbbell with T4 end loops of this study, a plot of d(Tm)/d ln
      [Na+] was constructed. Extrapolation of this data to n = 1 intersects with the
      value of d (Tm)/d ln [Na+] obtained for the alkyl-linked dumbbell, suggesting the
      salt-dependent stability of the alkyl-linked molecule behaves as though the
      duplex of this molecule were linked by end loops comprised of a single T residue.

PMID- 8268406
TI  - Studies of DNA dumbbells. V. A DNA triplex formed between a 28 base-pair DNA
      dumbbell substrate and a 16 base linear single strand.
AB  - CD spectra and melting curves were collected for a 28 base-pair DNA fragment in
      the form of a DNA dumbbell (linked on both ends by T4 single-strand loops) and
      the same DNA sequence in the linear form (without end loops). The central 16 base
      pairs (bp) of the 28-bp duplex region is the poly(pu) sequence: 5'
      AGGAAGGAGGAAAGAG-3'. Mixtures of the dumbbell and linear DNAs with the 16-base
      single-strand sequence 5'-TCCTTCCTCCTTTCTC-3' were also prepared and studied. At
      22 degrees C, CD measurements of the mixtures in 950 mM NaCl, 10 mM sodium
      acetate, 1 mM EDTA, pH 5.5, at a duplex concentration of 1.8 microM, provided
      evidence for triplex formation. Spectroscopic features of the triplexes formed
      with either a dumbbell or linear substrate were quite similar. Melting curves of
      the duplex molecules alone and in mixtures with the third strand were collected
      as a function of duplex concentration from 0.16 to 2.15 microM. Melting curves of
      the dumbbell alone and mixtures with the third strand were entirely independent
      of DNA concentration. In contrast, melting curves of the linear duplex alone or
      mixed with the third strand were concentration dependent. At identical duplex
      concentrations, the dumbbell alone melts approximately 20 degrees C higher than
      the linear duplex. The curve of the linear duplex displayed a significant
      pretransition probably due to end fraying. On melting curves of mixtures of the
      dumbbell or linear duplex with the third strand, a low temperature transition
      with much lower relative hyperchromicity change (approximately 5%) was observed.
      This transition was attributed to the melting of a new molecular species, e.g.,
      the triplex formed between the duplex and single-strand DNA molecules. In the
      case of the dumbbell/single-strand mixture, these melting transitions of the
      triplex and the dumbbell were entirely resolvable. In contrast, the melting
      transitions of the linear duplex and the triplex overlapped, thereby preventing
      their clear distinction. To analyze the data, a three-state equilibrium model is
      presented. The analysis utilizes differences in relative absorbance vs
      temperature curves of dumbbells (or linear molecules) alone and in mixtures with
      the third strand.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8268407
TI  - A conformational study of the dehydroalanine: dipeptide and homopolypeptide.
AB  - A molecular mechanics study of polydehydroalanine [poly-(delta Ala)] is
      presented. For this purpose the AMBER 3a program has been used to perform the
      calculations. With exception of the point charges, the parameters for the
      terminal groups were taken from AMBER 3a libraries, whereas those for the delta
      Ala residue from Alagona et al. [J. Comp. Chem. (1991) Vol. 12, pp. 934-942].
      Charges for the residue and terminal groups have been fitted from the MNDO
      electrostatic potential and scaled to achieve an ab initio 6-31G* quality.
      Calculations have been carried out using the continuous solvent approximation
      with three different dielectrics epsilon = 1, 1r, and 4r. The results show that,
      despite the preferred structure for the isolated residue is an extended
      conformation, a 310-helix is the preferred conformation in the solid state
      (epsilon = 1 and 1r), whereas a peculiar structure with psi = 0 degree is
      preferred with epsilon = 4r.

PMID- 8268408
TI  - The effects of Cu2+ and Pb2+ on the solution structure of calf thymus DNA: DNA
      condensation and denaturation studied by Fourier transform ir difference
      spectroscopy.
AB  - The interaction of calf thymus DNA with Cu2+ and Pb2+ was studied in aqueous
      solution at pH 6.5 with metal/DNA (P) (P = phosphate) molar ratios (r) 1/80,
      1/40, 1/20, 1/10, 1/4, 1/2, and 1, using Fourier Transform ir (FTIR)
      spectroscopy. Correlations between the ir spectral changes, metal ion binding
      mode, DNA condensation, and denaturation, as well as conformational features,
      were established. Spectroscopic evidence has shown that at low metal/DNA (P)
      molar ratios 1/80 and 1/40, copper and lead ions bind mainly to the PO2- of the
      backbone, resulting in increased base-stacking interaction and duplex stability.
      The major copper ion base binding via G-C base pairs begins at r > 1/40, while
      the lead ion base binding occurs at r > 1/20 with the A-T base pairs. The
      denaturation of DNA begins at r = 1/10 and continues up to r = 1/2 in the
      presence of copper ions, whereas a partial destabilization of the helical
      structure was observed for the lead ion at high metal ion concentration (r =
      1/2). Metal-DNA binding also results in DNA condensation. No major departure from
      the B-family structure was observed, upon DNA interaction with these metal ions.

PMID- 8268409
TI  - Overcrossing spectra of protein backbones: characterization of three-dimensional
      molecular shape and global structural homologies.
AB  - A procedure is developed and applied to characterize the global shape and folding
      features of the backbone of a chain molecule. The methodology is based on the
      following concept: the probability of observing a rigid placement of a backbone
      in 3-space as a projected curve with N overcrossings. The numerical computation
      of these probabilities allows one to construct the overcrossing spectrum of a
      macromolecule at a given configuration. Although the spectrum is built from the
      knowledge of the nuclear geometry of the main-chain atoms, the shape descriptor
      overlooks local geometrical features (such as distances and contacts) and
      provides a characterization of essential (topological) features of the overall
      fold, such as its compactness and degree of entanglement. In contrast with other
      shape descriptors, the present approach gives an absolute characterization of the
      configuration considered, and not one that is relative to an arbitrarily chosen
      reference structure. Moreover, it is possible to discriminate between folding
      features that otherwise may not be distinguished when using other geometrical or
      topological global descriptors. The overcrossing spectrum is proposed as a tool
      that complements current structural analyses of macromolecules, especially when
      monitoring structural homologies within a group of related or unrelated polymers.
      In this work, we apply the methodology to the analysis of proteins having the
      globin fold. The results are compared with those of other proteins exhibiting
      similar size and number of residues. Some basic properties of the spectra as a
      function of the chain length are also discussed.

PMID- 8268410
TI  - Biasing a Monte Carlo chain growth method with Ramachandran's plot: application
      to twenty-L-alanine.
AB  - In this paper, we explore the possibility of using experimental observations in
      the Monte Carlo chain growth method that we have previously developed. In this
      method, the macromolecule (peptide, protein, nuclei acid, etc.) is grown atom-by
      atom (or residue-by-residue, etc.) and partial chains are replicated according to
      their Boltzmann weights. Once the molecule completed, we are left with a
      Boltzmann-distributed ensemble of configurations. For long molecules, an
      efficient sampling of the (extremely large) phase space is difficult for obvious
      reasons (existence of many local minima, limited computer memory, etc.). In the
      case in which one is mainly interested in the low energy conformations, we have
      incorporated in the growth scheme experimental observations taken from the
      Protein Data Banks. More precisely, we have considered the case of twenty-L
      alanine and we have used the (experimental) Ramachandran's plot for this residue.
      The biased growth procedure goes as follows: (a) each time one adds along the
      main backbone chain, either a carbon atom belonging to a carbonyl group, or a
      nitrogen atom, its dihedral angle (theta) or (psi) is drawn with a probability
      law that reflects the experimental Ramachandran (theta, psi) plot; (b) the bias
      introduced in this way is canceled through an extra term in the energy
      (replication energy = true energy + bias energy); (c) the configurations,
      generated at T = 1000 K, are then energy minimized.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268411
TI  - The influence of hydration on the conformation of bovine serum albumin studied by
      solid-state 13C-NMR spectroscopy.
AB  - 13C proton-decoupled cross-polarization magic-angle spinning nmr spectra of
      bovine serum albumin are reported as a function of hydration. Increases in
      hydration level enhance the resolution of the peak centered at about 40 ppm but
      has little or no effect on the other spectral peaks. Hydration has little effect
      on either the rotating frame proton spin-lattice relaxation time or the cross
      relaxation time for any of the peaks, suggesting that the efficiency of dipolar
      coupling is largely preserved on hydration of the protein. Resolution enhancement
      of the peak at 40 ppm is not understood, but possible sources of the behavior
      include a decrease in the line width of contributing resonances from lysine
      epsilon carbons due to increased motional averaging on hydration, reordering of
      disulfide bridges, and titration shifts induced by hydration. Hydration of bovine
      serum albumin appears to have little effect on the distribution of conformations
      sampled by the protein so that the broad distribution of conformations observed
      in the dry state is also observed in the fully hydrated state. This is in
      contrast to lysozyme where significant ordering of the conformation is seen on
      hydration.

PMID- 8268412
TI  - Conformation and interactions of uteroglobin fragments 4-14 and 49-65 in aqueous
      solution containing surfactant micelles.
AB  - The conformation of two fragments of rabbit uteroglobin is described. The
      peptides are PRFAHVIENLL and PQTTRENIMKLTEKIVK, corresponding to helices I and IV
      in the crystal structure. CD shows that both peptides interact with sodium
      dodecyl sulfate (SDS) micelles and change their conformation to an alpha-helix.
      The helical content estimated from the CD band at 222 nm is about 40% in each
      peptide. Surface tension measurements show that both peptides lower the critical
      micellar concentration (cmc) of SDS, with a more dramatic effect in the case of
      helix I. This peptide by itself acts as a surfactant, and is able to interact
      with SDS even below the observed cmc, forming beta aggregates. Proton magnetic
      resonance (1H-nmr) suggests that flexible helices are present. The longest
      helical stretches compatible with 1H-nmr data extend from Phe6 to Leu14 for helix
      I and from Arg53 to Ile63 for helix IV.

PMID- 8268413
TI  - Quantitative two-dimensional NMR study of dermenkephalin, a highly potent and
      selective delta-opioid peptide.
AB  - Dermenkephalin, H-Tyr-(D)Met-Phe-His-Leu-Met-Asp-NH2, a highly potent and
      selective delta-opioid peptide isolated from frog skin, was studied in DMSO-d6
      solution by two-dimensional nmr spectroscopy, including the determination of NH
      temperature coefficients, the evaluation of 3J coupling constants from phase
      sensitive correlated spectroscopy (COSY) and the volumes of nuclear Overhauser
      effect (NOE) correlations. The two-dimensional NOE spectroscopy (NOESY) spectrum
      of dermenkephalin revealed sequential, medium-, and long-range effects. To put
      this information on a quantitative basis, special attention was devoted to J
      cross-peak suppression, quantification of the NOE volumes and analysis of the
      overlaps, normalization of the NOEs against diagonal peaks and H beta beta'
      geminal interactions. Although most of the dihedral angles deduced from the 3JN
      alpha coupling constants together with several Ni alpha i and alpha iNi+1 NOEs
      pointed to a partially extended peptide backbone, several NiNi+1 NOEs and beta
      iNi+1 interactions argued in favor of a folded structure. Moreover, several long
      range correlations of strong intensities were found that supported a close
      spatial proximity between the side chains of D-Met2 and Met6, Tyr1 and His4, Tyr1
      and Asp7, and His4 and the C-terminal amide group. In Phe, the g- rotamer in the
      side chain is deduced from the 3J alpha beta coupling constants and alpha beta
      and N beta NOE correlations. Whereas the amide proton dependency was not
      indicative of stable hydrogen bonds, the nonuniform values of the temperature
      coefficient may reflect an equilibrium mixture of folded and extended conformers.
      The overall data should provide realistic starting models for energy minimization
      and modelization studies.

PMID- 8268414
TI  - Acting on the cytokine balance to control auto-immunity and chronic inflammation.

PMID- 8268415
TI  - Interleukin-7, a major T-lymphocyte cytokine.
AB  - IL-7 is a single-chain 25 kDa protein first identified in bone marrow cultures
      through its pre-B cell growth factor properties, then also described as a potent
      T-lymphocyte growth factor. This review relates to the molecular and functional
      aspects of interleukin-7 (IL-7) and its receptor (IL-7R). We focused on the role
      of IL-7 in T-cell activation, cytotoxicity generation, leukemic cell growth and
      immunotherapy.

PMID- 8268416
TI  - Conversion of human fibroblasts to tissue macrophages by the Snyder-Theilen
      sarcoma virus (ST:FeSV): tumouricidal effects on K-562 and Daudi tumour cell
      lines in monolayers and in agar suspensions.
AB  - We have previously demonstrated the conversion of human fibroblasts (HF) to
      tissue macrophages by transduction with the Snyder-Theilen feline sarcoma virus
      (ST:FeSV) [1-3]. The ST:FeSV-induced TM have been characterized both
      phenotypically and functionally, including their tumouricidal potential against
      colon adenocarcinoma (LS 180) cells. The present results show that ST:FeSV
      induced TM produced significant lysis of K-562 tumour cells, but essentially no
      lysis of the Daudi tumour cells. Lysis of K-562 tumour cells by the ST:FeSV
      induced TM was considerably more effective in 1% than in 10% FCS. Addition of TNF
      alpha caused only a slight increase in the extent of lysis of K-562 tumour cells
      by the ST:FeSV-induced TM. Coincubation of the ST:FeSV-induced TM with K-562
      cells in agar medium resulted in the inhibition of tumour cell proliferation. The
      results indicate that ST:FeSV-induced TM are potent oncocytotoxic agents of K-562
      tumour cells, but are considerably less effective against the Daudi tumour cells.

PMID- 8268417
TI  - Human T lymphocyte activation by pokeweed mitogen induces production of TNF-alpha
      and GM-CSF and helper signaling by IL-1 and IL-6 results in IL-2-dependent T cell
      growth.
AB  - Pokeweed mitogen (PWM) is widely used as an inducer of polyclonal immunoglobulin
      production, but little attention has been paid to the effects of this lectin on T
      lymphocytes. In the present study, we analysed the effects of PWM on cytokine
      production by isolated resting T cells, as well as the involvement of cytokines
      as accessory signals in PWM-induced T cell activation. The conditions necessary
      to induce proliferation and production of IL-2, TNF-alpha and GM-CSF by purified
      T cells, completely depleted of monocytes, B cells and NK cells, could be created
      by immobilizing PWM through absorption on autologous red blood cells (PWM-RBC),
      while soluble PWM was totally inactive. IL-4 or IL-6 were not detected in the
      supernatants. In the presence of PWM-RBC (but not of soluble PWM), T cell
      proliferation and IL-2 production could strongly and consistently be enhanced by
      recombinant IL-1 beta and IL-6. On the other hand, the production of TNF-alpha
      and GM-CSF was not influenced by IL-1 beta and IL-6. Anti-Tac mAb (against the
      p55 IL-2R) completely inhibited T cell proliferative responses induced by PWM
      RBC, thus proving the IL-2-dependency of proliferation. There was no evidence for
      involvement of IL-4 as a growth factor. In conclusion, PWM directly stimulates
      human T cells and this results in production of several cytokines including IL-2,
      GM-CSF and TNF-alpha, and at least one of them (IL-2) is further upregulated by
      IL-1 beta/IL-6 from accessory cells.

PMID- 8268418
TI  - Sensitive and simple bioassay for human tumour necrosis factor-alpha.
AB  - A simple, sensitive, and specific in vitro bioassay is described for human tumour
      necrosis factor alpha (TNF-alpha). The system employs the U937 cell line
      incubated with 10 ng/ml actinomycin D for maximum sensitivity. This method allows
      the detection of less than 0.6 pg/ml of TNF-alpha and the log dose-response curve
      is linear at concentrations 0.6-250 pg/ml TNF-alpha. Highly sensitive subclones
      of U937 were obtained which were capable of detecting as little as 0.1 pg/ml TNF
      alpha. Finally, this bioassay demonstrates specificity by discriminating between
      TNF-alpha and TNF-beta.

PMID- 8268419
TI  - Role of the 75 kD- and 55 kD-receptors in tumour necrosis factor mediated
      cytotoxicity and its regulation by dexamethasone and by 1,25-dihydroxyvitamin D3
      in U937 cells.
AB  - The respective role of p55 and of p75 TNF receptors in mediating the constitutive
      or the regulated cytotoxic response of U937 cells was discriminated using
      monoclonal antibodies directed against each receptor type, respectively htr-9 and
      utr-1. Cytotoxicity was mediated by the p55 receptors. The p75 receptors were
      also implicated as it reduced 100 fold the maximal active dose of rTNF-alpha and
      15 fold the EC50 value. Dexamethasone potentiated and 1,25-dihydroxyvitamin D3
      abolished rTNF-alpha induced cell growth arrest and toxicity. Dexamethasone was
      required to be present for rTNF-alpha to be active. It increased the maximal
      response whether toxicity was mediated through only p55 or both p55 and p75
      receptors, without changing the respective EC50 values for rTNF-alpha. Therefore
      dexamethasone did not affect the interactions between p55 and p75 receptors nor
      between these receptors and their ligand, suggesting that it regulates the
      cytotoxicity at a post-receptor level. 1,25-dihydroxyvitamin D3 drove the
      promonocytic U937 cells resistant to rTNF-alpha by short-term effect. Comparing
      the effect of 1,25-dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 derivatives
      on the cytotoxicity to their effect on cell surface receptor expression, revealed
      that the capacity to induce resistance to rTNF-alpha was restricted to those
      steroids which down-regulated the p55 receptors. Therefore, resistance to rTNF
      alpha could be related to an early effect of 1,25-dihydroxyvitamin D3 on p55
      receptors. Finally, the results suggest that dexamethasone and 1,25
      dihydroxyvitamin D3 regulate TNF-alpha induced cytotoxicity by affecting
      processes probably related to the functions of the p55 receptors.

PMID- 8268420
TI  - The influence of recombinant mediators on in vitro IgG subclass secretion by
      peripheral blood mononuclear cells from patients with hypogammaglobulinemia and
      from normal donors.
AB  - Patients with hypogammaglobulinemia have recurrent infections and fail to produce
      protective antibodies. In order for B cells to mature into antibody producing
      cells, several other cell types such as macrophages and helper T lymphocytes must
      be involved. They secrete several mediators such as interleukin-1 (IL-1), IL-4,
      IL-5, IL-6 and interferon-gamma (IFN-gamma). These factors, as recombinant
      mediators, were tested to assess their ability to correct the immunoglobulin
      production defect in vitro from pokeweed mitogen (PWM) stimulated cultures of
      peripheral blood mononuclear cells (PBMC) from 11 patients with
      hypogammaglobulinemia, and from 10 normals as controls. In general, PBMC from
      hypogammaglobulinemic patients secreted very little Ig in cultures, and no
      mediator induced a statistically significant increase in the secretion of any IgG
      subclass. When assessed on an individual basis, one patient demonstrated a
      variable pattern of increase in total IgG, IgG1, and IgG3, secretion induced by
      various mediators, to within one standard deviation of the average secretion of
      normal PBMC cultured in PWM. In the case of the normal cells, IL-4, IL-6 and IL-1
      plus IL-4 were able to increase IgG2 secretion in culture with PWM. No increase
      in secretion of IgG1, IgG3 and IgG4 or total IgG was demonstrable however. Hence,
      although there is variability in responsiveness amongst the patients, there does
      not appear to be any one of these recombinant mediators which will correct the
      defect.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268421
TI  - Nobel Lecture. Protein phosphorylation and cellular regulation I.

PMID- 8268422
TI  - Divalent cation and lipid-protein interactions of biomembranes.
AB  - Divalent cations play an important role in the functions of biomembranes. This
      review deals with three topics: (1) Mg(2+)-mediated change in physical state of
      phospholipid induces conformation and activity change of reconstituted
      mitochondrial H(+)-ATPase, (2) a proper transmembrane Ca2+ gradient is essential
      for the higher enzymatic activity of adenylate cyclase, and (3) role of
      transmembrane Ca2+ gradient in the modulation of reconstituted sarcoplasmic
      reticulum Ca(2+)-ATPase activity.

PMID- 8268423
TI  - Effect of protease inhibitors and clenbuterol on the in vitro degradation of
      dystrophin by endogenous proteases in human skeletal muscle.
AB  - The in vitro degradation of dystrophin protein by endogenous proteases in human
      skeletal muscle has been investigated using a tissue homogenate assay system with
      subsequent protein analysis via SDS polyacrylamide electrophoresis and
      immunoblotting (using a monoclonal antibody to the central rod region of
      dystrophin). The rate of dystrophin degradation and nature of the proteolytic
      fragments formed at pH 5.5 and pH 7.5 (corresponding to the two major protease
      groups of relevance to intracellular protein catabolism) were broadly similar;
      incorporation of protease inhibitors in the above system suggested that Ca2+
      activated proteinase and cathepsin D are principally responsible for the
      degradation of dystrophin at pH 7.5 and pH 5.5 respectively. The rate of
      dystrophin degradation at pH 7.5 was reduced by approximately 20% in the presence
      of 10(-5) M clenbuterol, a beta-adrenoceptor agonist with therapeutic potential
      in the treatment of human muscle wasting diseases.

PMID- 8268424
TI  - Tetracyclines modulate cytosolic Ca2+ responses in the osteoclast associated with
      "Ca2+ receptor" activation.
AB  - We report the effects of tetracycline analogues on cytosolic Ca2+ transients
      resulting from application of ionic nickel (Ni2+), a potent surrogate agonist of
      the osteoclast Ca2+ "receptor". Preincubation with minocycline (1 mg/l) or a
      chemically modified tetracycline, 4-dedimethyl-aminotetracycline (CMT-1) (1 or 10
      mg/l), resulted in a significant attenuation of the magnitude of the cytosolic
      [Ca2+] response to an application of 5 mM-[Ni2+]. Preincubation with doxycycline
      (1 or 10 mg/l) failed to produce similar results. In addition, application of
      minocycline alone (0.1-100 mg/l) resulted in a 3.5-fold elevation of cytosolic
      [Ca2+]. The results suggest a novel action of tetracyclines on the osteoclast
      Ca2+ "receptor".

PMID- 8268425
TI  - The effect of tetracyclines on quantitative measures of osteoclast morphology.
AB  - We report the effects of the tetracycline analogues 4-dedimethylaminotetracycline
      (CMT-1) and minocycline on osteoclast spreading and motility. Both agents
      influenced the morphometric descriptor of cell spread area, rho, producing
      cellular retraction or an R effect (half-times: 30 and 44 minutes for CMT-1 and
      minocycline, respectively). At the concentrations employed, the tetracycline
      induced R effects were significantly slower than, but were qualitatively similar
      to, those resulting from Ca2+ "receptor" activation through the application of 15
      mM-[Ca2+] (slopes: -1.25, -0.18, and -4.40/minute for 10 mg/l-[CMT-1], 10 mg/l
      [minocycline] and 15 mM-[Ca2+], respectively). In contrast, the same tetracycline
      concentrations did not influence osteoclast margin ruffling activity as described
      by mu, a motility descriptor known to be influenced by elevations of cellular
      cyclic AMP. Thus, the tetracyclines exert morphometric effects comparable to
      changes selectively activated by occupancy of the osteoclast Ca2+ "receptor"
      which may act through an increase in cytosolic [Ca2+].

PMID- 8268426
TI  - The position of a double-lumen tube should be routinely determined by fiberoptic
      bronchoscopy.

PMID- 8268427
TI  - Post-thoracotomy epidural analgesia: lumbar or thoracic placement?

PMID- 8268428
TI  - A quality improvement study of the placement and complications of double-lumen
      endobronchial tubes.
AB  - To assess the complications of conventional and fiberoptic endobronchial
      intubations using reusable (Leyland, London) and disposable (Rusch, Waiblinger,
      Germany; Sheridan, Argyle, NY) double-lumen tubes (DLTs), endobronchial
      intubations occurring over a 12-month period were prospectively studied at this
      hospital. Residents working with staff anesthesiologists placed either left or
      right reusable (Leyland) or disposable (Rusch or Sheridan) DLTs. The DLT used,
      the use of fiberoptic bronchoscopy (FOB), findings at FOB if used during the
      intubation or operation, and complications occurring during the case (SpO2 < 90%,
      peak inflation pressure > 40 cm H2O, air trapping, poor lung isolation, and
      airway trauma) were recorded. Two hundred thirty-four intubations were analyzed
      (102 right, 132 left; 70 Leyland reusable DLTs, 66 Rusch disposable tubes, and 98
      Sheridan tubes). Physical signs alone were used to confirm tube position more
      frequently when Leyland tubes were placed compared with disposable tubes (79% v
      39%, P < 0.0001). Rusch and Sheridan DLTs had similar rates of conventional
      placement. Nineteen percent of reusable tubes and 44% of disposable tubes
      required position adjustments using FOB during the initial intubation (P =
      0.0002). Disposable tubes also more commonly required readjustment using FOB
      during the operation (30% v 7%, P < 0.0005). Complications occurred in 42/234
      patients (18%). The frequency of specific complications was: decreased SpO2, 9%;
      increased airway pressures, 9%; poor lung isolation, 7%; air trapping, 2%, and
      airway trauma, 0.4%. Right-sided Sheridan DLTs had a statistically higher
      incidence of malposition, resulting in poorer lung isolation.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8268429
TI  - Comparison of thoracic and lumbar epidural infusions of bupivacaine and fentanyl
      for post-thoracotomy analgesia.
AB  - Epidural analgesia, via either a thoracic or lumbar route, is commonly used to
      provide postoperative analgesia following thoracotomy for pulmonary resection,
      but little data indicate which location is better in terms of postoperative
      analgesia, side effects, or associated complications. In this study, 45 patients,
      who were scheduled to have epidural analgesia and undergo a lateral thoracotomy,
      were randomized to receive either a thoracic or a lumbar catheter. Pain
      assessments and routine clinical data were recorded to determine if either
      thoracic or lumbar epidural catheters provided superior analgesia, fewer side
      effects, or fewer complications. This study found no statistical difference in
      pain relief or side effects between lumbar and thoracic epidural analgesia for
      post-thoracotomy pain. An increased infusion rate (6.4 +/- 1.9 v 5.1 +/- 1.4
      mL/h, P = 0.02) was required in the lumbar group to achieve equivalent analgesic
      levels.

PMID- 8268430
TI  - Preoperative interpleural administration of sufentanil or bupivacaine reduces
      intraoperative intravenous sufentanil requirements during thoracotomy.
AB  - The efficacy of interpleural administration of sufentanil, 50 micrograms, was
      compared with that of 150 mg of bupivacaine, 0.5%, with epinephrine, 5
      micrograms/mL, or saline, in 30 patients (N = 10 in each group) undergoing
      lateral thoracotomy. Sufentanil, bupivacaine, or saline was administered
      interpleurally after induction of anesthesia with sufentanil, 1 microgram/kg
      intravenously, and thiopental, 2 to 5 mg/kg. Anesthesia was maintained with
      nitrous oxide, 66%, and halothane, 0.3% inspired concentration. Supplementary
      intravenous sufentanil, 25 micrograms, was given whenever the systolic arterial
      blood pressure increased more than 15 mmHg above the preoperative value, heart
      rate exceeded 90 beats/min in the absence of hypovolemia, or when other autonomic
      or somatic signs of inadequate anesthesia occurred. The additional intravenous
      sufentanil requirement and the incidence of hypotension were compared between the
      groups. All patients in the placebo group needed supplementary sufentanil.
      Significantly fewer patients in the interpleural sufentanil (N = 1, P < 0.0002)
      and bupivacaine (N = 1, P < 0.0002) groups required supplementary sufentanil
      compared to the placebo group (N = 10). The time from interpleural administration
      of the study drug to the first administration of postoperative analgesic was
      significantly longer (P < 0.001) in the sufentanil group (228 +/- 72 min) and
      bupivacaine group (242 +/- 76 min) compared to the placebo group (141 +/- 50
      min). It was concluded that interpleural administration of either sufentanil or
      bupivacaine contributes to intraoperative analgesia during thoracotomy.

PMID- 8268431
TI  - Pain management and spirometry following thoracotomy: a prospective, randomized
      study of four techniques.
AB  - Forty-five patients who underwent anterolateral and posterolateral thoracotomy
      were studied to compare the relative efficacy of cryoanalgesia, epidural
      morphine, intrapleural analgesia, and intravenous morphine for relief of
      postoperative pain and prevention of deterioration in pulmonary function.
      Spirometry (FEV1, FVC) was performed preoperatively and postoperatively.
      Patients' pain was assessed using the 0 to 100 mm visual analog scale. Because
      intravenous morphine was used to supplement pain relief in the patients who
      received intrapleural analgesia and cryoanalgesia, total morphine use was
      compared to that administered to patients in the intravenous morphine group.
      Epidural morphine was found to offer better pain relief than the other treatment
      modalities. There were no differences in spirometric testing between the groups
      at any time during the study. Although the number of evaluable patients was
      insufficient to draw definitive conclusions, 12-week follow-up suggested a
      difference in the incidence of post-thoracotomy pain syndrome in patients who
      received cryoanalgesia. It is concluded that post-thoracotomy pain is best
      relieved with epidural morphine, compared to intrapleural analgesia,
      cryoanalgesia, and parenteral morphine. There was no change in the deterioration
      in spirometric tests after thoracotomy, nor was there any advantage offered by
      cryoanalgesia or intrapleural analgesia over intravenous morphine, with respect
      to pain relief.

PMID- 8268432
TI  - Disconnection of the ventilatory system does not prevent pleural lesions during
      sternotomy.
AB  - In previous studies pleurotomy has seldom been reported as a complication of
      sternotomy and, therefore, the incidence is unknown. Factors increasing or
      decreasing the risk of pleurotomy also have not been studied properly. In a
      prospective, randomized trial, performed during 14 consecutive months from 1988
      until 1989, the incidence of pleurotomy and its possible risk factors were
      studied in 712 patients undergoing median sternotomy for cardiac and mediastinal
      procedures. The overall incidence of pleurotomy was 14.7%. Chronic obstructive
      pulmonary disease, the use of positive end-expiratory pressure, and continuation
      or discontinuation of the ventilatory system did not affect the incidence. A
      surgeon-related risk factor could be significantly identified (P < 0.001). In
      conclusion, disconnection of the ventilatory system during sternotomy has been
      shown to have no influence on the pleurotomy rate and its continued use is no
      longer valid.

PMID- 8268433
TI  - Efficacy of capnometry in ventilatory management of cardiac patients.
AB  - The ability of capnometry to prevent hypercarbia and to safely help in weaning
      post-cardiac surgery patients was investigated. The first group, 60 patients, had
      arterial blood gases (ABG) determined after each new ventilator setting. The
      corresponding end-tidal CO2 (PETCO2) was recorded and PaCO2-PETCO2 gradients were
      established at each ABG determination. The initial gradient was maintained during
      ventilation in the patient. A later gradient, determined when the patient was
      waking, was used to wean. The next 50 patients, the second group, had responses
      to ventilator changes determined solely by capnometry. ABG were routinely drawn
      only to establish the maintenance and weaning PaCO2-PETCO2 gradients. The initial
      gradients of 8.43 +/- 3.45 (mean +/- SD) and 7.65 +/- 2.24 mmHg, in the first and
      second groups, narrowed to 1.27 +/- 3.79 and 2.21 +/- 3.96 mmHg, respectively,
      when the patients were ready to wean. All patients in both groups were safely
      weaned. Patients in the second group had fewer ABG determinations, 3.78 +/- 1.30
      v 5.40 +/- 1.97, a decrease of 1.62 (95% confidence interval 1.54 to 1.70). No
      patient was hypercarbic. The study shows that capnometry can be used to safely
      wean patients, decrease the number of ABG, and prevent hypercarbia.

PMID- 8268434
TI  - Mechanical ventilation in the prone position for acute respiratory failure after
      cardiac surgery.
AB  - Ten patients with acute respiratory failure (ARF) after coronary artery bypass
      grafting were studied during conventional mechanical ventilation in the supine
      and in the prone position. Impaired gas exchange was defined as an inspired
      oxygen fraction (FIO2) greater than 0.5 to maintain an arterial oxygen tension
      (PaO2) > or = 70 mmHg, an alveolar-arterial PaO2 gradient (PA-aO2) > 200 mmHg and
      a venous admixture (QVA/QT) > 15% during mechanical ventilation with a tidal
      volume (VT) = 10 to 12 mL/kg, frequency (f) = 10 to 15 VT/min, inspiratory
      expiratory (I:E) ratio = 0.5, and positive end-expiratory pressure (PEEP) of 5 to
      7.5 cm H2O. In the supine position, systemic and pulmonary hemodynamics were in
      the normal range, but oxygenation was severely impaired. In all patients thoracic
      computed tomography scans were obtained and revealed crest-shaped bilateral
      densities in the dependent lung regions. FIO2 of 0.67 +/- 0.22 was required to
      maintain a PaO2 greater than 70 mmHg during mechanical ventilation in the supine
      position. Under these conditions PA-aO2 and QVA/QT were 362 +/- 153 mmHg and 32.5
      +/- 8.3%, respectively. CO2 elimination was not severely affected. The patients
      were turned into the prone position after an average of 30.6 +/- 5.4 hours
      postoperatively and ventilated with unchanged VT, f, PEEP, and inspiratory
      expiratory ratio for 26.7 +/- 11.7 hours (range, 10 to 42 hours). A second
      cardiopulmonary status was obtained within 2 to 5 hours of ventilation in the
      prone position.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268435
TI  - Effect of continuous positive airway pressure applied by face mask on right
      ventricular function after cardiac surgery.
AB  - The effect of respiratory therapy with continuous positive airway pressure (CPAP)
      on right ventricular function 24 hours after elective cardiac surgery was
      evaluated in patients with or without severe coronary artery disease. The first
      group included 10 patients following coronary artery bypass graft (CABG) surgery,
      and the second group included 10 patients following aortic valve replacement
      (AVR) without preexisting coronary artery disease. Patients of both groups had
      preoperative left ventricular ejection fractions above 40%. CPAP was applied by
      face mask at a flow rate of 20 L/min with 40% oxygen in nitrogen and with a
      positive end-expiratory pressure of 12 cmH2O. Right ventricular function was
      estimated at end-expiration by a fast-response thermodilution cardiac output
      catheter. The results demonstrate that in both groups of patients, CPAP did not
      significantly modify right ventricular indices, ejection fraction, end-systolic
      and end-diastolic volume indices, and stroke volume index, indicating that CPAP
      can safely be applied after elective cardiac surgery in patients with or without
      severe coronary artery disease and preoperative left ventricular ejection
      fractions above 40%. Furthermore, the concomitant postoperative intravenous
      infusion of nitroglycerin (to all 10 patients of the CABG group and to 4 patients
      of the AVR group) counteracted the expected beneficial effect of CPAP therapy on
      arterial oxygenation.

PMID- 8268436
TI  - Central hemodynamics and right ventricular function after coronary artery bypass
      surgery. A comparison of prostacyclin, sodium nitroprusside, and nitroglycerin
      for treatment of postcardiac surgical hypertension.
AB  - The aim of this study was to compare the effects of prostacyclin on central
      hemodynamics and right ventricular function to the more widely used vasodilators
      sodium nitroprusside (SNP) and nitroglycerin (NTG), and to investigate whether
      prostacyclin is more selective to the pulmonary vascular bed compared to SNP and
      NTG after coronary artery bypass surgery. Twelve patients with two-vessel or
      three-vessel coronary artery disease and an ejection fraction > 0.5 were
      included. Hemodynamic measurements were made postoperatively in the intensive
      care unit using a pulmonary artery fast-response ejection fraction/volumetric
      thermodilution catheter. The aim was to control and maintain mean arterial blood
      pressure around 75 to 80 mmHg with each drug. After a 10-minute infusion of each
      drug at a stable infusion rate, central hemodynamic variables as well as right
      ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV) and
      ejection fraction (RVEF) were measured or derived in triplicate. The average
      infusion rates of SNP, NTG, and prostacyclin were 2.3 +/- 0.8 micrograms/kg/min,
      12.6 +/- 6.0 micrograms/kg/min and 20.0 +/- 0.5 ng/kg/min, respectively. Cardiac
      output, stroke volume, RVEDV, and central filling pressures were highest for
      prostacyclin compared to both NTG and SNP. Systemic vascular resistance (SVR) was
      lowest for prostacyclin but the effects on pulmonary vascular resistance (PVR)
      were comparable to that of SNP. The PVR/SVR ratio was significantly lower with
      both SNP and NTG when compared to prostacyclin. RVEF did not differ among the
      three drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268437
TI  - Hemodynamic effects of amrinone and colloid administration in children following
      cardiac surgery.
AB  - Amrinone was used as the sole vasoactive medication in 9 of 14 children (aged 5
      months to 8.25 years) given the drug following open repair of congenital cardiac
      lesions. Four children received a concomitant dopamine infusion and one infant
      had the infusion stopped after 5 hours for low mean arterial pressure (49 mmHg).
      In the 10 children receiving only amrinone, cardiac index increased 21% (range, 0
      to 94%) after a total loading dose of 4.5 mg/kg given over 1 hour. Four of 14
      patients (29%) required dopamine infusions to maintain mean arterial pressure
      over 55 mmHg and in these children cardiac index increased from baseline and was
      maintained during the amrinone infusion. Preload was held constant by
      administration of whole blood or plasmanate during amrinone loading; a decrease
      in systemic vascular resistance index was seen resulting in a stable arterial
      blood pressure. Minimal chronotropic effect was seen and no arrhythmias occurred.
      The sole child with postoperative pulmonary hypertension had a beneficial
      decrease in pulmonary artery pressure, increase in cardiac index, and stable
      systemic blood pressure during amrinone use. Cardiac index changes during
      amrinone loading in these children were variable and less clearly related to
      serum levels than reported in adults. Pharmacokinetic analysis in 12 children
      showed a clearance of 3.4 mL/min/kg, a volume of distribution of 1.65 L/kg, and
      an elimination half-life of 5.75 hours. Decreases in platelet counts were seen in
      6 children and platelet transfusion was needed in 1; thus, serial platelet counts
      should be monitored.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268438
TI  - Role of ischemia-reperfusion on myocardial cyclic AMP and cyclic AMP
      phosphodiesterase: effects of amrinone on regional myocardial force and
      shortening.
AB  - This study tested the hypothesis that a reperfused ischemic myocardial region of
      the dog heart would be unable to increase its function in response to amrinone, a
      specific cyclic AMP phosphodiesterase (cAMP-PDE) inhibitor, due to loss of cAMP
      PDE activity in the region. The global contractility (+dp/dtmax), regional
      percent shortening (ultrasonic crystals), and developed force (miniature force
      gauge) were measured on a continuous basis throughout a 6-hour experiment and
      regional blood flow (radioactive microspheres) in open-chest pentobarbital
      anesthetized mongrel dogs. The left anterior descending coronary artery (LAD) was
      isolated and ligated for 2 hours and allowed to reperfuse for 4 hours. This
      myocardial region was compared to a nonischemic region supplied by the circumflex
      artery. At the end of the 4-hour reperfusion period, 9 dogs were treated with
      amrinone (5 mg/kg) and three dogs were not treated with amrinone. The hearts were
      rapidly excised and frozen in liquid nitrogen. Cyclic AMP and cAMP-PDE activity
      was determined in homogenates of myocardial tissue. Blood flow decreased during
      occlusion in the LAD region and returned toward control with reperfusion. Flow
      increased nonsignificantly with amrinone. the basal cyclic AMP content of the two
      regions was not different. The cAMP-PDE activity was reduced 24% in the LAD
      region compared to the control region. There were no ischemia-induced changes in
      the enzyme characteristics. These experiments demonstrated increased global
      function in the ischemic reperfused myocardium after amrinone was administered
      (dP/dtmax: 2092 +/- 538 to 3277 +/- 688 mmHg/sec).(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268439
TI  - Beneficial effect of amrinone on the size of acute regional ischemia in isolated
      rabbit hearts.
AB  - The effect of inotropes on myocardial ischemia is difficult to predict because
      they may influence the determinants of myocardial O2 demand and O2 supply
      differently. Several PDE-inhibitors have been reported to possess antiischemic
      properties related to their hemodynamic and O2-sparing effects. To assess whether
      PDE-inhibitors also possess direct cardioprotective properties, the effects of
      amrinone (2.5 x 10(-5) mol/L) in comparison to isoproterenol (5 x 10(-9) mol/L)
      and ouabain (1.5 x 10(-7) mol/L) were studied in isolated rabbit hearts perfused
      according to Langendorff at a constant pressure (70 cmH2O) and electrically
      driven at a constant pacing rate. Regional ischemia was induced by coronary
      artery ligation and quantified by epicardial NADH fluorescence. All substances
      significantly increased the actively developed left ventricular pressure to a
      similar extent (+20%) (P < 0.05). Coronary flow was significantly decreased by
      ouabain (-15%) and significantly increased by isoproterenol (+25%) and
      particularly by amrinone (+50%) (P < 0.05). Neither ouabain nor isoproterenol
      significantly changed the intensity or the distribution pattern of NADH
      fluorescence, whereas the size of the ischemic zone was significantly reduced by
      amrinone (-25%) (P < 0.05). The PDE-inhibitor amrinone was shown to possess a
      direct cardioprotective effect by improving myocardial perfusion and O2 supply in
      isolated rabbit hearts.

PMID- 8268440
TI  - The anesthetic management of a patient with a thoracic aortic aneurysm that
      caused compression of the left mainstem bronchus and the right pulmonary artery.

PMID- 8268441
TI  - Spontaneous pneumothorax in early pregnancy: successful management by
      thoracoscopy.

PMID- 8268442
TI  - Hemodynamic collapse during thoracoscopy.

PMID- 8268443
TI  - The effect of rapid volume expansion on hypoxemia in patients with tetralogy of
      Fallot.

PMID- 8268444
TI  - Thoracic epidural analgesia: physiologic effects and clinical applications.

PMID- 8268445
TI  - Case 3--1993. Combined abdominal aortic aneurysm resection and cholecystectomy
      following prior heart transplantation.

PMID- 8268446
TI  - Pro: midazolam is the sedative of choice to supplement narcotic anesthesia.
AB  - Having examined the options for adjuvant drug use during cardiac anesthesia, it
      becomes increasingly apparent that midazolam is "the drug" of choice and that
      supplementation with an opioid is an ideal adjuvant. In the hands of experienced
      cardiac anesthesiologists, the majority of the drugs discussed could provide
      adequate anesthesia with outcomes that would be difficult to distinguish, with
      the exception of awakening and time to extubation. Regardless of the inability to
      differentiate overall outcome, when comparing ease of providing complete
      "balanced" anesthesia, minimal cost increase, ease of use, hemodynamic stability,
      reliability of amnesia and ability to decrease narcotic requirement and allow
      early extubation, midazolam is a clear winner. Given as a continuous infusion or
      a bolus, potent opioids such as alfentanil, fentanyl or sufentanil enhance the
      amnestic and hypnotic effect of midazolam, decreasing the required dose. In
      addition, the combination of midazolam and narcotics decreases the catecholamine
      response that either one alone would produce. This removes the necessity of
      marked narcotic overdose required when narcotics alone are used. The result of
      this anesthetic combination is a technique that can be used in the majority of
      cardiac patients regardless of their ventricular performance, allowing options
      for earlier awakening, earlier extubation and decreased ICU stay. The goal of
      complete "balanced" anesthesia is best achieved with continuous infusions of
      midazolam and opioids. Accepting recall of intraoperative events as a necessary
      evil is unacceptable in the stable cardiac surgery patient.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8268447
TI  - Con: midazolam is not the sedative of choice to supplement narcotic anesthesia.

PMID- 8268448
TI  - Organ replacement by man-made devices.

PMID- 8268449
TI  - An unusual hemodynamic tracing during pulmonary artery catheter insertion.

PMID- 8268450
TI  - The Bronchocath CPAP system is safe when properly used.

PMID- 8268451
TI  - Use of inhaled nitric oxide to reduce pulmonary hypertension after heart
      transplantation.

PMID- 8268452
TI  - Excessive dobutamine-induced tachycardia in the asthmatic cardiac patient:
      possible potentiation by theophylline therapy.

PMID- 8268453
TI  - Do patients undergoing closed mitral valvotomy need elective ventilation in the
      postoperative period?

PMID- 8268454
TI  - Effect of 5-lipoxygenase inhibitors on the anti-IgE-induced contraction of
      passively sensitized human bronchus in vitro.
AB  - We assessed the effect of 5-lipoxygenase inhibitors on the contraction of human
      bronchial ring segments passively sensitized with IgE in vitro. Contraction was
      induced by increasing doses of anti-IgE (0.01-0.5 micrograms/ml) in the presence
      of the antihistamine mepyramine. Zileuton and MK-886 (10 microM) significantly
      inhibited the dose-related contraction to anti-IgE as compared with solvent
      (DMSO). At the highest dose of anti-IgE used, contraction reached 10.3 and 9.6%
      of the maximal carbachol contraction, respectively, as compared with 30.3% for
      solvent. Maximal carbachol contraction was unaffected. These results suggest a
      potential beneficial effect of 5-lipoxygenase inhibitors in anaphylactic
      reactions in man.

PMID- 8268455
TI  - 4-Hydroxynonenal content lower in brains of 25 month old transgenic mice carrying
      the human CuZn superoxide dismutase gene than in brains of their non-transgenic
      littermates.
AB  - Basic peroxidation in brains of normal 2 month old mice was compared to that in
      brains of 25 month old mice by measurement of 4-hydroxy-2-nonenal and protein
      carbonyl contents. No significant age-related differences in 4-hydroxy-2-nonenal
      were observed, showing that lipid peroxidation is not a determining factor in
      cerebral aging. However, protein carbonyls increased with age in brains,
      indicating accumulation of age-related cell constituent damage. The role of
      excess CuZn superoxide dismutase in basal lipid peroxidation in mouse brains was
      studied by comparison of eight 25 month old transgenic mice and eight non
      transgenic littermates. Higher 4-hydroxy-2-nonenal concentrations were found in
      normal mouse brains. These data suggest an increased protective role of CuZn
      superoxide dismutase against lipid peroxidation in transgenic mouse brains.

PMID- 8268456
TI  - Interactions between sensory neuropeptides and lipid mediators in the airways.
AB  - The local release of sensory neuropeptides from capsaicin-sensitive primary
      afferents elicits prominent motor and inflammatory actions in mammalian airways.
      This neurogenic inflammation can contribute to the pathophysiology of asthma and
      airway hyperreactivity. In this review evidence will be presented regarding the
      involvement of this peptidergic neural pathway in the mediation of some pulmonary
      actions of lipid mediators such as eicosanoids and PAF.

PMID- 8268457
TI  - Human recombinant lipocortin 1 (annexin 1) has anticoagulant activity on human
      plasma in vitro.
AB  - Lipocortin 1 is a member of a group of calcium and phospholipid binding proteins
      named lipocortins (Di Rosa et al. (1984) Prostglandins 28, 441-442) and also
      known as annexins (Crumpton (1990) Nature 345, 212). In this study we have shown
      that human recombinant lipocortin-1 can increase the activated partial
      thromboplastin time but not the prothrombin time of human plasma in vitro. This
      effect is dose and time dependent and is reversed by polyclonal anti-lipocortin-1
      antibodies. To our knowledge, this is the first demonstration that the human
      recombinant protein has the same activity as the native protein on human plasma.

PMID- 8268458
TI  - Production of lipid mediators in experimental keratitis of rabbit eye.
AB  - The inhibitors of prostaglandin (PG) or leukotriene (LT) synthesis and
      antagonists of platelet-activating factor (PAF) or LTs are inhibitory in
      experimental keratitis and clinical symptoms of keratitis are reproduced by
      application of these lipid mediators. This suggests that PGE2, LTB4, LTD4, and
      PAF are involved in experimental immunogenic and toxic keratitis. The objective
      of the present study is the measurement of the concentrations of lipid mediators
      in the aqueous humour and their release by the cornea and iris during keratitis.
      In both inflammatory models the concentrations of PGE2, LTB4, LTD4, and PAF in
      the aqueous humour were significantly increased as compared to their controls.
      The release of PGE2, LTB4 and LTD4 from the cornea, and of PGE2, LTB4, and PAF
      from the iris was significantly increased compared to that from control tissues.
      The results are consistent with a role for these lipid mediators in the
      inflammatory models. Combined therapeutic use of synthesis inhibitors or
      antagonists of these mediators in eye inflammation seems possible and may serve
      as an alternative to topical corticosteroid therapy.

PMID- 8268459
TI  - Differential sensitivity of mouse strains to platelet activating factor-induced
      vasopermeability and mortality: effect of antagonists.
AB  - In the present study, we have compared the responses to platelet-activating
      factor (PAF) of A/J and BALB/c inbred mouse strains. Two PAF-induced events were
      analyzed: increased vasopermeability, measured by extravasation of Evans blue dye
      (EB), and mortality. PAF injected into the peritoneal cavity induced a bell
      shaped dose-response curve of EB extravasation in both strains of mouse. In A/J
      mice, maximal EB extravasation was reached with 0.1 microgram of PAF/mouse,
      whereas in BALB/c mice maximal extravasation was attained at a 10-fold greater
      PAF concentration. PAF-induced mortality also differed among these mouse strains;
      the LD50 was 12.1 micrograms/kg in A/J and 21.2 micrograms/kg in BALB/c mice.
      Thus, these strains differ significantly regarding both events mediated by PAF.
      Surprisingly, the F1 hybrid (A/J x BALB/c) mice were as sensitive as the A/J
      strain to PAF-induced extravasation but were as resistant as the BALB/c mice to
      PAF-induced mortality. The effects of the PAF antagonists BN 52021 and WEB 2086
      were compared in the F1 hybrids. It was found that 1.0 mg/kg of WEB 2086 affected
      PAF-induced extravasation at almost all PAF doses tested (0.03-3.0 micrograms)
      while 15 mg/kg of BN 52021 was only effective at doses of PAF below 0.3
      microgram. Both antagonists prevented PAF-induced mortality. Our results indicate
      that the two events induced by PAF may be controlled by different genes.

PMID- 8268460
TI  - 5-Lipoxygenase activity in the human pancreas.
AB  - Low levels of 5-lipoxygenase (5-LO), the first committed enzyme in the synthesis
      of leukotrienes (LTs), have been reported in the porcine pancreas. We have
      quantitated 5-LO activity in subcellular fractions of pancreas samples from three
      human donors. 5-LO activity was detectable in all samples, although enzyme
      activity was lower than in human leukocytes. 5-LO in human pancreas samples
      displayed highest specific activity in membrane fractions, and did not require
      arachidonic acid (AA) addition for activity. These unusual characteristics of
      pancreatic 5-LO appear to be due, at least in part, to the presence of
      unesterified AA in the pancreas samples. Western blot analysis demonstrated that
      the human pancreas contains low levels of 5-lipoxygenase-activating protein
      (FLAP) in addition to 5-LO.

PMID- 8268461
TI  - PAF-releasing factor in human serum and inflammatory exudate.
AB  - A factor responsible for releasing PAF produced in stimulated human
      polymorphonuclear leukocytes, which had been previously reported in human serum
      (Miwa et al. (1992) J. Immunol. 148, 872-880), was also confirmed to be present
      in inflammatory exudate. PAF-releasing factor, partially purified from human
      serum, was shown to possess higher affinity for PAF than for triacylglycerol,
      cholesterol ester, fatty acid or phosphatidylcholine. PAF bound to this factor
      aggregated washed rabbit platelets to the same extent as that bound to BSA, but
      was difficult to be hydrolyzed using PAF acetylhydrolase. These observations
      strongly suggest that PAF-releasing factor functions as a PAF carrier in blood
      and in the inflammatory response.

PMID- 8268462
TI  - Secretory non-pancreatic group II phospholipase A2: role in physiologic and
      inflammatory processes.

PMID- 8268463
TI  - Sphingosine and sphingosine 1-phosphate in cellular proliferation: relationship
      with protein kinase C and phosphatidic acid.
AB  - Previous studies from our laboratory have shown that sphingosine (Zhang et al.
      (1990) J. Biol. Chem. 265, 76-81) and sphingosine 1-phosphate (Zhang et al.
      (1991) J. Cell. Biol. 114, 155-167), metabolites of membrane sphingolipids,
      stimulate release of calcium from internal sources and increase proliferation of
      quiescent Swiss 3T3 fibroblasts acting in a fundamentally different, protein
      kinase C-independent pathway. The mitogenic effect of sphingosine was accompanied
      by an increase in the levels of phosphatidic acid (PA), a potent mitogen for a
      variety of cell types, that may function as an intracellular second messenger
      (Zhang et al. (1990) J. Biol. Chem. 265, 21309-21316). Sphingosine also induced
      early increases in sphingosine 1-phosphate (SPP) levels that preceded the
      increase in PA (Desai et al. (1992) J. Biol. Chem. 267, 23122-23128). SPP itself
      produced a more rapid increase in PA, thus suggesting that it may mediate the
      effects of sphingosine on PA accumulation. The concentration dependence for the
      formation of PA induced by SPP correlated with its effect on DNA synthesis.
      Similar to sphingosine, SPP also stimulated the activity of phospholipase D,
      although a significant effect was observed at a much lower concentration.
      However, in contrast to previous reports with sphingosine, SPP did not inhibit
      the PA phosphohydrolase activity in cell homogenates. Thus, in addition to its
      effect on mobilization of calcium, SPP can increase the level of PA, most likely
      via activation of phospholipase D. We suggest that SPP mediates the effect of
      sphingosine on PA accumulation in Swiss 3T3 fibroblasts and may regulate cellular
      proliferation by affecting multiple transmembrane signaling pathways.

PMID- 8268464
TI  - Phospholipase D-mediated hydrolysis of phosphatidylcholine: role in cell
      signalling.
AB  - Studies carried out in many laboratories have demonstrated the activation of
      phospholipase D (PLD) by a variety of receptor agonists and in many cell types.
      The signal-dependent formation of phosphatidic acid (PA), by PLD-catalyzed
      hydrolysis of phosphatidylcholine (PC), may represent a novel and ubiquitous
      signal transduction pathway in mammalian cells. The mode(s) of coupling between
      agonist receptors and PLD activation are not well understood. Studies utilizing
      NIH-3T3 fibroblasts indicated that PLD activation by different mitogens involves
      distinct mechanisms. Protein kinase C (PKC) seems to play a role both as a
      mediator and as a modulator of PLD activation. The role of PKC was further
      examined in Swiss/3T3-derived fibroblasts which stably overexpress PKC-alpha. In
      these cells, both basal and agonist-stimulated PLD activity are higher than in
      control cells. In vitro analysis of PLD activity in detergent-solubilized cell
      membranes, utilizing exogenous C6-NBD-PC as fluorescent substrate, showed nearly
      2-fold higher activity in membranes from cells that overexpress PKC-alpha. These
      results suggest that PKC-alpha may play a role in regulating PLD expression. The
      PLD product PA was identified as a precursor of 'late phase' diacylglycerol
      which, at least in some cases, was temporally correlated and causally related to
      the sustained activation of PKC. However, PA may itself act as an intracellular
      messenger in its own right, although immediate targets for its action have not
      yet been identified. Activation of phosphoinositide-phospholipase C, PLD and
      phospholipase A2 seems to comprise a signaling cascade which is typically
      utilized by most (if not all) Ca(2+)-mobilizing agonists.

PMID- 8268465
TI  - Cytosolic PLA2: mRNA levels and potential for transcriptional regulation.

PMID- 8268466
TI  - A successful physician-led multidisciplinary approach to process improvement for
      inpatient chemotherapy.
AB  - In 1991, Henry Ford Hospital established a physician-led, multidisciplinary
      chemotherapy DRG task force charged with examining and improving the clinical and
      support processes relating to inpatient chemotherapy. While the goal of this
      effort was to improve cost management, quality improvement philosophy and methods
      were applied. This task force developed two short-stay protocols, reducing the
      length of hospitalization from three days to one for high-dose cisplatin
      regimens, and from five to only two days for combined chemotherapy/radiation
      therapy regimens. This article shares insights regarding the types of
      improvements and methods that were used, the effective involvement of physicians,
      and the use of administrative and staff support to accelerate the improvement
      effort and leverage clinicians' time.

PMID- 8268467
TI  - Evolution of hospital industrial engineering: from scientific management to total
      quality management.
AB  - Industrial engineering applications in the hospital industry first began in 1910.
      This paper traces the evolution of hospital industrial engineering in five
      distinct phases. For each of the major phases, this paper presents the
      contributions made by industrial engineers. Many of the techniques advocated by
      industrial engineers are now being taught to hospital employees as hospitals
      introduce total quality management (TQM) within the health-care industry. TQM
      introduction has meant a new role for industrial engineers, as that of a teacher,
      coach, and a facilitator. This new role holds much promise for the improvement of
      quality and productivity in health care.

PMID- 8268468
TI  - Cross-functional clinical teams: significant improvement in operating room
      quality and productivity.
AB  - This paper will describe a successful application of Quality Improvement concepts
      to the complex Perioperative System at an academic medical center in the
      Northeast. The initiation of multi-disciplinary teams (including surgeons,
      anesthesiologists, and nurse managers) will be discussed, as will the steps,
      skills, and techniques employed. The paper will catalogue keys to success from
      those observed during this and five similar recent Quality Improvement
      engagements facilitated by such a process.

PMID- 8268469
TI  - Inter-hospital mortality and morbidity variation in Pennsylvania.
AB  - A 1986 Pennsylvania law requires the public disclosure of hospital mortality and
      morbidity rates. This study of hospital admissions in 1989 and 1990 examines the
      variation in these health-outcome indicators for the 10 most frequently occurring
      DRGs in the adult medical service in a sample of 20 Pennsylvania hospitals. These
      mortality and morbidity rates are adjusted for admission severity, DRG, age, and
      sex, using a logistic regression model. The null hypothesis of no significant
      variation among hospitals is rejected by the statistically significant (p < 0.01)
      results of a likelihood ratio test on the hospital variables in logit models for
      both mortality and morbidity. Test results also show that 4 (20 percent) of 20
      hospitals have statistically significant (p < 0.05) adjusted mortality rates, and
      4 (20 percent) of 20 hospitals have significant morbidity rates. Such information
      may impact hospital management practices in a variety of ways.

PMID- 8268470
TI  - A statistical evaluation of mammography: crucial questions for health systems.
AB  - This article reviews data on incidence and mortality rates from breast cancer and
      provides the results from applications of Bayes' Theorem and a test of
      homogeneity to investigate the efficacy of mammographic screening for breast
      cancer. The results of our analyses indicate that the accuracy and effectiveness
      of mammographic screening for breast cancer are debatable. Consequently, we
      identify crucial unanswered questions for health systems about the heavy reliance
      on mammography. We recount the current recommendations, standards of practice,
      and utilization of mammography for breast cancer screening. Finally, we question
      the language used to describe the conclusions of these studies.

PMID- 8268471
TI  - Physician-Directed Diagnostic and Therapeutic Plans: a quality cure for America's
      health-care crisis.
AB  - The most effective way to improve quality is to reduce variation in the processes
      of providing a service. Physician-Directed Diagnostic and Therapeutic (PDDT)
      Plans are a proven methodology for reducing variation in clinical processes and
      improving the quality of care. A major part of the PDDT Plan process is the
      development of a critical pathway. Critical pathways are an application of Total
      Quality Management (TQM) principles to clinical care which have provided clear,
      tangible results in those hospitals committed to this process. These pathways
      define the processes, timelines and responsibilities associated with the
      patient's clinical needs from preadmission to post discharge. Representatives of
      the various health-care professions involved in treating the specified patient
      populations work together, led by a physician, to define the processes of care.
      When completed, everyone involved in treating the patient understands what is to
      be done, by whom, and when. The pathways allow clinicians to plan ahead and let
      the patient and family know what to expect. Through establishing standards of
      care, these critical pathways also reduce the uncertainty of treatment decisions
      and free physicians from having to practice defensive medicine, and thus reduce
      cost. While the most visible outcome of this process is the actual PDDT Plan, it
      is not necessarily the most important. The very process of designing the pathway
      improves intra- and interdisciplinary communication, and fosters teamwork.

PMID- 8268472
TI  - [On the recent abrupt rise in the number of foreign females in the AIDS
      surveillance in Japan].
AB  - AIDS surveillance in Japan has recently witnessed an abrupt increase in the
      number of foreign females infected with HIV, which soared from 2 in 1989 to 274
      in 1992. To clarify underlying causes for such a phenomenon anti-HIV seropositive
      rates and anti-HIV testing rates of foreign females who visited hospitals or
      clinics were investigated either by a retrospective medical records survey or by
      direct serological tests in several districts in the Tokyo metropolitan area.
      These studies revealed that seropositive rates of foreign females, mostly from
      Thailand, ranged between 1.0-5.0% during Jan. 1990-Apr. 1993, varying between
      districts and with a slight increase over the period. The proportion of foreign
      females who underwent anti-HIV test was found to have markedly increased from
      around 10% in 1990 to 75% in 1991 in spite of testing rates for syphilis or
      gonorrheal infection remaining unchanged during the same period. Their sexual
      behaviour was also studied and found that most of them were engaged in sex
      activities without using condom. These results suggest (1) The number of foreign
      females with HIV infection could have been considerably underestimated by the
      surveillance because in 1991, when the surveillance detected only 105 foreign
      females, around 600 or more foreign female infectees may have existed in Japan as
      estimated by multiplying the 3% infection rate with 20,000, the estimated female
      Thai population illegally residing in Japan by the end of 1991.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8268473
TI  - [Risk factors of hepatitis C virus infection].
AB  - In order to clarify the risk factors of hepatitis C virus (HCV) infection, past
      medical histories, family histories of liver disease, and lifestyle factors
      (smoking and drinking habits) were compared between anti-HCV positive cases and
      anti-HCV negative controls. Studies were 433 anti-HCV positive cases and 298
      negative controls, all of whom were out-patients with chronic hepatitis or liver
      cirrhosis. The findings were contrasted with the risk factors of hepatitis B
      virus (HBV) chronic infection. Multiple logistic regression analysis revealed the
      following findings. Prevalence of anti-HCV among patients with chronic hepatitis
      or liver cirrhosis increased with age, while prevalence of HBsAg decreased with
      age. Histories of blood transfusion were closely associated with the risk of HCV
      infection. Adjusted relative risk for patients with a history of blood
      transfusion was estimated to be 2.97 (95% confidence intervals: 1.88-4.71) in
      comparison with the risk for patients without it. Any family history of liver
      disease was not related with the risk of HCV infection, while mother's history of
      liver disease was significantly associated with the risk of chronic HBV infection
      (adjusted relative risk was 2.96 with 95% confidence intervals: 1.32-6.62).

PMID- 8268474
TI  - [Hyperlipidemia, hypoalphalipoproteinemia and liver dysfunction in Japanese
      school-age children with obesity].
AB  - Three hundred and twenty nine obese children (206 boys, 123 girls) whose obesity
      index were above 40% were screened among 6,278 school-age children living in
      Ibaraki Prefecture. Six hundred and fifty-eight school-age children without
      obesity were used as controls. The mean levels of total cholesterol and
      triglyceride of obese boys were significantly higher than those of control boys.
      The mean levels of HDL-cholesterol of both boys and girls with obesity were
      significantly lower than those of controls. Hypercholesterolemia,
      hypertriglyceridemia and hypoalphalipoproteinemia in the boys with obesity were
      significantly more frequent than those in control boys. In the girls with
      obesity, hypoalphalipoproteinemia was significantly more frequent than that in
      control girls. Liver dysfunction (GPT > or = 40 IU/l) in obese children was
      significantly more frequent than in controls: Although none of controls had liver
      dysfunction, 24.8% of obese boys and 11.4% of obese girls had liver dysfunction.
      These findings indicated that atherogenic dyslipidemias and liver dysfunction
      were common in Japanese school-age children with obesity, especially in boys.

PMID- 8268475
TI  - [Factorial construct validity of a measurement scale of fatigue in junior high
      school students].
AB  - To investigate factorial construct validity of a measurement scale of fatigue
      symptoms in junior high school students, a questionnaire which consisted of
      Cumulative Fatigue Symptoms Index (CFSI) and Psychological Condition Test (PCT)
      was administered on 289 students in Okinawa. Reliability coefficients were 0.607
      0.811 for CFSI scales. A principal factor analysis with varimax rotation was
      applied to CFSI. In boys, 4 factors were extracted; general psychological
      symptoms, fatigue, emotional instability, and decreased morale and vitality. In
      girls, 4 factors were extracted; depression and anxiety, decreased morale and
      vitality, fatigue, and irritability. The same procedure was applied to PCT. In
      boys, 4 factors were extracted; negative feeling, vigor, inferiority complex, and
      fatigue. In girls, 4 factors were extracted; negative feeling, anger, vigor, and
      fatigue. Among factors derived from CFSI and PCT, the fatigue factor of CFSI was
      correlated with that of PCT. The factors concerning psychological symptoms of
      CFSI were correlated with those of PCT. However, the vigor factor of PCT was not
      correlated with any other factors. These results suggest that CFSI in junior high
      school students had factorial construct validity.

PMID- 8268476
TI  - [Dietary fiber intake among the general population in 25 prefectures].
AB  - The per capita daily intake of dietary fiber in 25 prefectures was calculated
      from measured values of dietary fiber in each food according to the modified
      Southgate method and the modified Prosky method. Results obtained were as
      follows; In the calculated values according to the modified Southgate method,
      mean per capita daily dietary fiber intake was highest in Gunma 20.5 g and lowest
      in Okinawa (13.5 g). On the other hand with Prosky method, dietary fiber intake
      was highest in Gunma (19.3 g) and lowest in Hyogo (12.4 g). Therefore, dietary
      fiber intake was higher in eastern Japan than in western Japan. In calculated
      values according to the modified Southgate method, the largest consumption was
      noted with rice at 30%. On the other hand, in Prosky method, vegetables were
      noted as the largest and rice ranked second. The mean per capita daily intake of
      hemicellulose was noted at 50% of the whole, cellulose at 30-35% and lignin at 15
      20%.

PMID- 8268477
TI  - [Factors influencing self-registration in a bone-marrow bank: analysis of data
      from a population survey in Shiga Prefecture].
AB  - A population survey of awareness and attitudes regarding a bone-marrow bank was
      carried out in 19 cities and towns of Shiga prefecture in July 1991, to identify
      factors that would promote donor self-registration among the general population.
      The survey involved 832 residents (416 men and 416 women) selected as follows:
      Each social welfare commissioner of the cities and towns selected a total of
      eight residents, one male and one female from each of 4 age groups (20-29, 30-39,
      40-49 and 50-59 years old). The questionnaires were distributed and collected by
      the social welfare commissioners with an overall response rate of 97.4%. Subjects
      answered questions regarding their experience and desire to participate in social
      volunteer activities, knowledge about bone-marrow banks, their perception of it's
      necessity, and whether they would participate in a bone-marrow bank, etc. A total
      of 25.9% of male and 20.6% of female subjects stated they had a desire to
      register in a bone-marrow bank. From the result of multiple regression analysis,
      the characteristics of those who showed interest in registration in a bone-marrow
      bank included having heard of the bone-marrow bank, experience in social
      volunteer activity, experience in blood donation, knowledge of bone-marrow
      transplantation and living in a town where need for establishment of a bone
      marrow bank was widely discussed among residents. In the promotion of the idea of
      a bone-marrow bank, the role of motivating people to participate in voluntary
      blood donation and other social volunteer activities appears to be
      important.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268478
TI  - [Isolation of Methylobacterium spp. from drinking tank-water and resistance of
      isolates to chlorine].
AB  - On bacteriological examination of 100 samples of drinking tank water, standard
      plate count bacteria (36 degrees C, 24 h) and coliforms were not detected,
      conforming to the water quality criteria under the Water Supply Law. Ninety-five
      percent of test samples had concentrations of residual chlorine exceeding 0.1
      mg/l. However, one characteristic heterotroph was isolated from 70% of these
      water samples. The bacteria showed glucose non-fermentative Gram-negative rods
      and formed pink colonies when cultured on standard agar medium at 30 degrees C
      for 7 days. It was oxidase-positive, catalase-positive and motile. Furthermore,
      utilization of methyl alcohol was a characteristic. From these characteristics,
      it was identified as genus Methylobacterium. The isolated Methylobacterium of 118
      strains were divided into 60 types using 20 biochemical tests. Thirty
      Methylobacterium strains were examined for tolerance to chloride by contact with
      free residual chlorine of 0.1 mg/l concentration for 5 min. Considerable
      resistance to residual chlorine was evident. The TW-7 strain showed especially
      high tolerance, even surviving contact at 1.0 mg/l concentration of free residual
      chlorine for 10 minutes.

PMID- 8268479
TI  - [Benefits of a community oriented fluoride mouth rinsing program].
AB  - The benefits of a school-based fluoride mouth rinsing in a community dental
      health program were evaluated. In village "M", children from 4 to 14 years old
      have been participating in a school-based fluoride mouth rinsing program since
      1974. In addition, an informal association for dental health of children was
      inaugurated in 1975 to support the community dental health program. In village
      "K", there were no fluoride mouth rinsing programs. However, the usual dental
      health education conducted in all schools was similar in both communities. In
      order to compare these two communities, dental examinations were carried out in
      1990. The total number of subjects from 6 to 14 years old was 331 in village "M"
      and 408 in village "K". In village "M" for longitudinal comparison, 12-year-olds,
      1,054 in total, were examined annually from 1974 to 1990. The DMFT-index in all
      subjects in village "M" was 76.1% lower than in village "K". In village "M", the
      DMFT-index in 1990 decreased 79.0% compared to 1974. The economic benefits
      obtained through the caries reduction were evaluated. In 1990 the mean cost of
      dental treatment for subjects 14 years old was 27,840 yen per person in village
      "K" and 4,248 yen in village "M". The cost-benefit ratio was 18.8 and the cost
      effectiveness ratio was 137 yen. These remarkable benefits from the prevention of
      dental caries appears to have been mainly obtained due to the participation of
      children aged 4 to 14 years old in a school-based fluoride mouth rinsing program.

PMID- 8268480
TI  - [Guidance of community mental health training for psychiatry residents].
AB  - Compared to other advanced countries, the field of mental health in Japan is
      characterized by a large hospitalized to general population ratio and a long mean
      hospitalization period. This is in large part attributable to the lack of
      appropriate housing as well as occupational recreational centers after discharge.
      At the same time the education of psychiatric medical staff has focused on the
      hospital environment, with little attention devoted to training at centers of
      community mental health. This hospital-dominant approach has been difficult to
      shed, and has persisted since the WHO report of Dr. Clark in 1968. Paralleling
      the introduction of the certified doctor system, at the Japanese Society of
      Psychiatry and Neurology recently, the manner of postgraduate training for
      psychiatrists and attempts to reform it were debated. In the midst of this
      debate, a consensus has emerged that study of community mental health is one of
      the minimum requirements to become a full-fledged psychiatrist. However, no
      adequate community mental health training programs have been established at any
      institution. At Nara Medical University hospitals, considerable weight has been
      placed on community mental health training, with such a training program designed
      and put into practice. In the present report, this training program is introduced
      and interim results reported, and the problems associated with community mental
      health training are discussed.

PMID- 8268481
TI  - [Current situation and its chronological change of preparedness for AIDS at
      general hospitals in Japan].

PMID- 8268482
TI  - [An evaluation of functional training services for the aged in Sendai].

PMID- 8268483
TI  - Epidemiology of bluetongue in Central America and the Caribbean: initial
      entomological findings. Regional Bluetongue Team.
AB  - Forty-four species of Culicoides (Diptera: Ceratopogonidae) were caught in insect
      light traps during the first 2 years of studies on the epidemiology of bluetongue
      virus in the Caribbean and Central America. Traps were operated near sentinel
      ruminants which were bled monthly for serologic evaluation and then virus
      isolation. More than 570,000 individuals were identified. Culicoides insignis
      Lutz accounted for 90% of the catch, C. filarifer Hoffman/C. ocumarensis Ortiz
      5%, C. furens Poey 3% and C. pusillus Lutz 2%. Other species accounted for less
      than 1% of the total catch. Sentinel ruminants became seropositive when C.
      insignis populations were high at many study sites. At a few sites C. pusillus
      and C. filarifer/C. ocumarensis were predominant or were present in large numbers
      during seroconversions of sentinels. Virus isolations were obtained from sentinel
      ruminants during times when these same species were present in large populations.

PMID- 8268484
TI  - The nutritional state of male tsetse flies, Glossina pallidipes, at the time of
      feeding.
AB  - The feeding intervals of tsetse flies have been estimated from the nutritional
      state of flies caught in traps. However, such estimates have been disputed on the
      grounds that traps catch a biased, hungry sample of the flies which are seeking
      hosts and will feed. In this paper we present data on the nutritional state of
      tsetse flies caught approaching and feeding on oxen. Individual oxen were
      surrounded with an incomplete ring of electric nets which caught Glossina
      pallidipes Austen that were approaching, departing unfed and departing fed from
      an ox. Non-teneral males caught in this way were analysed for their fat and
      haematin contents. The feeding interval was estimated from a comparison of the
      frequency distributions of the pre- and post-feed haematin contents of the flies
      which fed. The former was not measured directly, and was deduced from the
      frequency distributions of the haematin contents of the male flies caught
      approaching and departing unfed from the oxen, since it is assumed that the
      departing unfed and fed flies together form a sample of the approaching flies.
      There was no difference between the frequency distributions of haematin contents
      of flies caught approaching and departing unfed, and therefore the pre-feed
      haematin contents of the males which fed should have the same frequency
      distribution. Comparison of this distribution with that of the post-feed haematin
      contents of the males which fed indicated that the majority of male G.pallidipes
      were returning to feed after digesting on average 1.4 log haematin units of the
      previous bloodmeal.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268485
TI  - Autumn southward 'return' migration of the mosquito Culex tritaeniorhynchus in
      China.
AB  - Direct evidence for a southward 'return' migration in autumn of the mosquito
      Culex tritaeniorhynchus in China was obtained by aerial sampling with a net
      suspended from a balloon. In a preliminary study between 2 and 20 September 1990
      at Jiangpu, near Nanjing, in Jiangsu Province, 11 females and 4 males of this
      species were taken at heights of 150-250 m. During 17-26 October 1991 at
      Dongxiang in northern Jiangxi Province, 44 mosquitoes (8 males, 36 females) were
      caught in the aerial net at heights of 80-380 m in northeasterly winds (E-NNW).
      Most of the specimens were flying within the subsiding air-mass behind a cold
      front. Cx tritaeniorhynchus was the only species identified (31 females) among
      the mosquitoes from Dongxiang. Of 24 females dissected, 17 had N stage ovaries-
      interpreted as diapause, five had stage I ovaries, one had stage II ovaries, and
      one was gravid (stage V), but none was freshly blood-fed. Cx tritaeniorhynchus is
      the main vector of Japanese viral encephalitis in China, and it is possible that
      the virus is reintroduced to northern temperate areas in spring by northward
      migration of infected Cx tritaeniorhynchus females.

PMID- 8268486
TI  - Effects of adult body size on fecundity and the pre-gravid rate of Anopheles
      gambiae females in Tanzania.
AB  - The influence of adult body size on the pre-gravid state and fecundity was
      studied in Anopheles gambiae Giles females hand-caught inside houses and virgin
      females collected as pupae in Tanzania. Blood-fed mosquitoes were kept for 2-3
      days before dissection and examination for insemination and ovarian condition.
      Those females which did not develop eggs were classified as pre-gravid. The
      number of mature eggs in those mosquitoes which became gravid was counted. Virgin
      females were fed and kept for egg maturation in the laboratory. Wing-length of
      females was measured as an index of mosquito size. The overall pre-gravid rate in
      the resting An.gambiae population was found to be 21% and, of these, 66% had been
      inseminated. In the virgin females the pre-gravid rate was 92.6%. The mean wing
      length of wild females which became gravid was significantly larger than those
      which remained pre-gravid. There was a positive correlation between fecundity and
      wing-length. Smaller females tended to require two or three bloodmeals to
      facilitate completion of the first gonotrophic cycle. The critical size
      permitting oviposition from the first blood-meal was a wing-length of 3 mm.

PMID- 8268487
TI  - Impact of permethrin-impregnated mosquito nets compared with DDT house-spraying
      against malaria transmission by Anopheles farauti and An.punctulatus in the
      Solomon Islands.
AB  - In villages of northern Guadalcanal in the Solomon Islands, where the predominant
      malaria vector is An.farauti No. 1 and An.puctulatus is also involved, malaria
      transmission rates were compared for three zones: (1) non-intervention: 438
      people in seventeen villages; (2) residual DDT house-spraying two cycles per
      year: 644 people in thirty villages; (3) bednets impregnated with permethrin 0.5
      g/m2 twice per year, used by 580 people in sixteen villages. Regular DDT spraying
      in zones 1 and 3 had been withdrawn 18 months previously. Malariological blood
      smear surveys of children aged 1-9 years in August 1986 to January 1987 showed a
      mean baseline malaria parasite rate of 38% (32/84). By February 1988, 18 months
      after introduction of impregnated bednets, the Plasmodium falciparum infection
      rate in children was lowest in the zone using impregnated bednets (21% of 29),
      intermediate in the untreated zone (29% of 34) and highest in the DDT zone (46%
      of 53), but these differences were not statistically significant. P. vivax
      infection rates were 9-14%. Using ELISA tests for malaria circumsporozoite
      antigen in the vectors, overall positivity rates were 0.7% of 49,902 An.farauti
      and 2.54% of 118 An.punctulatus, comprising 228 P.falciparum and 124 P.vivax
      infections. In the study zones, vector positivity rates were 0.93% of 31,615
      An.farauti in the untreated zone; 0.32% of 16,883 An.farauti in the DDT zone;
      0.07% of 1404 An.farauti and 2.54% of 118 An.puctulatus in the impregnated bednet
      zone. here was no significant correlation between malaria parasite rates in the
      vectors and the children.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268488
TI  - Amplification of tick-borne encephalitis virus infection during co-feeding of
      ticks.
AB  - Following engorgement of Rhipicephalus appendiculatus larvae on guinea-pigs
      infected with tick-borne encephalitis (TBE) virus, none of the engorged larvae or
      emergent nymphs contained detectable infectious virus. However, one of twelve
      pools, each containing three of the unfed nymphs, was positive when screened by
      polymerase chain reaction (PCR), indicating a low prevalence of TBE virus
      infection in the unfed nymphs. After engorgement of the nymphs on four uninfected
      guinea-pigs, 19/24 (79%) fed nymphs from one guinea-pig and 4/25 (16%) fed nymphs
      from a second guinea-pig were infected; all the ticks examined from the other two
      guinea-pigs were uninfected. The results suggest that TBE virus was transmitted
      from a low proportion of infected nymphs (infected as larvae) to uninfected
      nymphs as they fed together on an uninfected guinea-pig. Such amplification of
      the initial infection, at the population level, could play an important role in
      maintaining TBE virus infections in nature, particularly if there is a low level
      of vertical transmission from one tick generation to the next.

PMID- 8268489
TI  - Prevalence of Theileria in the tick Hyalomma detritum detritum in the Doukkala
      region, Morocco.
AB  - The overall prevalence of Theileria species, mainly, if not exclusively,
      T.annulata, in 901 Hyalomma detritum detritum collected from cattle in the
      Doukkala region of Morocco over a period of 2 years was 21.5%. The quantity of
      infection (number of sporoblasts per infected tick) followed the negative
      binomial distribution with between one and 250 sporoblasts per infected tick.
      Infected ticks were found in eight of fourteen areas examined whilst T.annulata
      was present in all fourteen. There were significant differences in both the
      prevalence and the quantity of infection between ticks collected from different
      farms, and between nymphs collected in the autumn from these farms, and moulted
      in the laboratory, and adults collected in the following summer. The prevalence,
      but not the quantity, of infection was higher in female than in male ticks. No
      correlations were established between infection of engorged nymphs and the breed,
      sex and Theileria piroplasm parasitaemia of the host animal. However, calves
      infected a greater proportion of nymphs than adult cattle and the heavier the
      infestation of nymphs on an animal, up to a plateau, the higher the prevalence of
      infection in those nymphs. There were no differences in infection between ticks
      moulted at 24 degrees C and 37 degrees C, after the engorged nymphs had been
      stored at 18 degrees C to simulate over-wintering.

PMID- 8268490
TI  - Effective population size and persistence of Anopheles arabiensis during the dry
      season in west Africa.
AB  - The way that the malaria vectors Anopheles arabiensis and An.gambiae survive the
      dry season in sub-saharan Sahel or northern Savanna areas of Africa remains
      enigmatic. We examined this problem by calculating the effective sizes (Ne) of
      An.arabiensis populations for several locations in West Africa. An
      indirect/genetic procedure was used, comparing gene frequencies at several time
      intervals. The amount of drift which occurred provides an estimate of Ne. Most
      estimates of Ne were approximately 2000 individuals, probably close to the yearly
      minimum. This supports the hypothesis that populations of An.arabiensis in this
      region are continuous throughout the year, with many individuals surviving
      through the dry season, perhaps in a physiologically altered state, rather than
      extinction or severe bottlenecks during the dry season, followed by
      recolonization by a few individual survivors or immigrants in the subsequent
      rainy season.

PMID- 8268491
TI  - Description and biology of Trichopria painteri n.sp. (Hymenoptera: Diapriidae), a
      solitary parasitoid of Stomoxys calcitrans (Diptera: Muscidae) from Harare,
      Zimbabwe.
AB  - Taxonomic description and life history are given of Trichopria painteri n.sp.
      (Hymenoptera: Diapriidae), a solitary endoparasitoid that emerged from Stomoxys
      calcitrans (L.) (Diptera: Muscidae) pupae collected at an agricultural
      installation near Harare, Zimbabwe, Africa. Although its low level of parasitism.
      high immature mortality and short adult life span would require augmentative
      releases of T.painteri, this parasitoid could reduce isolated field populations
      of S.calcitrans to an acceptable level within several weeks.

PMID- 8268492
TI  - Barrier spraying to control the malaria vector Anopheles albimanus: laboratory
      and field evaluation in the Dominican Republic.
AB  - To develop a new strategy for control of exophilic/exophagic malaria vectors
      which rest on peridomestic foliage, Anopheles albimanus was used for laboratory
      bioassays of mosquito adulticides applied to various vegetation types. Of the
      three classes of insecticide tested, the pyrethroid (permethrin at 112 g/ha)
      showed greater foliar persistence than either the carbamate (bendiocarb at 340
      g/ha) or the organophosphorus compound (malathion at 277 g/ha). Field evaluation
      of barrier spraying against An.albimanus was evaluated in rural villages of
      southwest Dominican Republic during 1989. The pyrethroid deltamethrin was sprayed
      aerially for ultra-low volume application at treatment rates of 17-19 g a.i./ha
      in a radius of 500 m around two villages. An.albimanus were monitored by light
      traps and human bait collections at both treated villages, compared with two
      similar untreated villages, up to 9 nights posttreatment. Densities of female
      An.albimanus were significantly reduced in the sprayed villages for at least 8 or
      9 nights. Further evaluation of barrier spraying is recommended to determine
      optimal pyrethroid formulations and applications rates, their impact on non
      target fauna and efficacy against malaria transmission.

PMID- 8268493
TI  - A comparison of susceptibility of two allopatric populations of Glossina
      pallidipes for stocks of Trypanosoma congolense.
AB  - A colony of Glossina pallidipes Austen which originated from Nguruman, Rift
      Valley Province, Kenya, was significantly more susceptible to infection (19.3%)
      with a stock of Trypanosoma congolense Broden isolated from G. pallidipes in
      Nguruman than a colony of the same species which originated from Shimba Hills,
      Coast Province, Kenya (5.6%). Male G.pallidipes from Nguruman were significantly
      more susceptible than females to this T.congolense stock whilst the
      susceptibility of both sexes of G.pallidipes from Shimba Hills did not differ
      significantly. All six goats on which six infected G.pallidipes fed singly (three
      tsetse per colony) became infected. Similarly, the G.pallidipes colony of
      Nguruman origin was significantly more susceptible to infection (16.4%) with a
      stock of T.congolense isolated from G.pallidipes in Shimba Hills than the colony
      of Shimba Hills origin (4.9%). The susceptibility of the sexes of G.pallidipes
      from both the colonies to this stock of T.congolense did not differ
      significantly. Again, all six goats on which six infected G.pallidipes fed singly
      (three tsetse per colony) became infected. If the observed differences in
      susceptibility of the two G.pallidipes colonies reflect transmission of
      trypanosomes by the two allopatric populations of tsetse in the field, then the
      epidemiology of congolense-trypanosomiasis in livestock must differ between these
      two areas of Kenya endemic for trypanosomiasis.

PMID- 8268494
TI  - Confirmation that Plasmodium falciparum has aperiodic infectivity to Anopheles
      gambiae.
AB  - In preparation for field studies of transmission-blocking malaria vaccines, a
      study was carried out to determine whether P. falciparum infections obtained in
      An. gambiae blood-fed at 16.00 hours were quantitatively similar to infections
      obtained at 23.00 hours. Using a group of children aged 5-12 years from villages
      at Ahero, near Kisumu in Kenya, 71/74 (96%) of whom were found to be positive for
      P.falciparum parasitaemia, one batch of fifty colony-bred An.gambiae females were
      fed on volunteers at 16.00 hours and another batch at 23.00 hours. No
      statistically significant differences were found in the proportions of mosquitoes
      becoming infected, the numbers of children infecting mosquitoes or the mean
      numbers of malaria oocysts developing in mosquitoes blood-fed at the different
      times. Because mosquito infections obtained by day (16.00 hours) are equivalent
      in quantity to those obtained at night (23.00 hours), experimental infections can
      be carried out in the afternoon, when it is most convenient, rather than during
      the night.

PMID- 8268495
TI  - Phylogenetically distant symbiotic microorganisms reside in Glossina midgut and
      ovary tissues.
AB  - Many blood-feeding insects, including tsetse flies (Diptera: Glossinidae),
      harbour intracellular bacterial symbionts. Using isolates from tissues of several
      Glossina species and diagnostic DNA oligonucleotide primers, a polymerase chain
      reaction (PCR) based assay was designed to identify symbiotic bacteria. Those
      inhabiting the midgut of Glossina were found to belong to the gamma subdivision,
      whereas ovarian Proteobacteria were of the alpha subdivision--probably genus
      Wolbachia (Rickettsiaceae). The presence of Wolbachia-like Rickettsia in the
      ovaries of G.morsitans subspecies may help to explain the maternally inherited
      incompatibility of some crosses within this species.

PMID- 8268496
TI  - Comparative morphology of rodent flea eggs in China.

PMID- 8268497
TI  - Entomological evaluation of ivermectin mass treatment against onchocerciasis.

PMID- 8268498
TI  - Anopheles balabacensis (Diptera: Culicidae), a vector of Wuchereria kalimantani
      (Nematoda: Onchocercidae) in east Kalimantan (Borneo), Indonesia.

PMID- 8268499
TI  - Micromorphology of the prestomal teeth and feeding behaviour of Musca autumnalis,
      M.larvipara and M.osiris (Diptera: Muscidae).

PMID- 8268500
TI  - Laparoscopic Nissen fundoplication: report of first 15 cases.
AB  - Performance of a Nissen fundoplication laparoscopically for gastroesophageal
      reflux disease offers significant advantages such as reduction in hospital stay,
      postoperative recovery time, and return to work time. Early experience with
      laparoscopic Nissen fundoplication is presented.

PMID- 8268501
TI  - Laparoscopic vs. open wedge biopsy of the liver.
AB  - This study was a post-hoc evaluation of laparoscopic versus open wedge biopsy of
      the liver performed as part of prospective phase I antibiotic trial. Consenting
      patients undergoing elective cholecystectomy were enrolled in a protocol which
      required samples of bile, blood, the gallbladder, and 1 gram of liver tissue. The
      study occurred during the evolution of laparoscopic surgery. Liver biopsy was
      done in standard fashion and laparoscopic liver biopsy was accomplished with
      cauterized scissors. Twenty-four patients, 4 male and 20 female averaging 42.1
      years of age, were entered in this study. Eighteen patients underwent
      laparoscopic surgery and six patients underwent open surgery. They did not differ
      significantly in age (43.9 vs 42.1 years), operating room time (58.3 min vs 55.8
      min), or complications (2/18 vs 2/6). Patients undergoing laparoscopic surgery,
      however, did have a shorter hospital stay (1.1 days vs 3.5 days, p < 0.001). All
      liver specimens were considered adequate. There were no complications related to
      the liver biopsy. Laparoscopic wedge biopsy of the liver is both a feasible and
      viable alternative to open wedge biopsy.

PMID- 8268502
TI  - Laparoscopic technique for repair of paraesophageal hiatal hernias.
AB  - Paraesophageal hernias represent a distinct group of hiatal hernias characterized
      by their potential for devastating complications. Between 1976 and 1992, a total
      of 270 surgeries were performed for hiatal hernias at Scripps Clinic, La Jolla,
      California, of which 33 were pure paraesophageal, without reflux. Starting in
      September 1991, a laparoscopic technique was used for repair of five out of six
      attempted cases of paraesophageal hiatal hernias. The closure of the hiatal
      defect was accomplished with mesh stapled to the edges of the hiatus in front of
      the esophagus. A gastropexy was added attaching the stomach to the diaphragm.
      This procedure proved to be technically easy and safe, and resulted in less
      discomfort and faster recovery of the patients when compared to the open
      procedure. This laparoscopic repair should be considered as a good alternative to
      the open techniques for paraesophageal hiatal hernias without reflux.

PMID- 8268503
TI  - Rectopexy.
AB  - Many surgical procedures have been described for the management of full-thickness
      rectal prolapse. Currently, the three procedures most frequently used are
      anterior resection with or without suture rectopexy, transabdominal mesh fixation
      without resection, and perineal proctosigmoidectomy. Only the latter procedure
      avoids a laparotomy, and the mesh fixation technique has a high incidence of
      severe constipation postoperatively. Recently, there have been two reports of
      laparoscopic mesh fixation for rectal prolapse which were successful. However,
      the long-term concerns are probably very similar. Therefore, the purpose of this
      paper is to report a series of 6 laparoscopic-assisted anterior resections
      performed for rectal prolapse at Ferguson-Blodgett Hospital from January 1, 1992
      through October 30, 1992. There were no perioperative mortalities and the only
      complication was a port site bleed which required re-exploration. The mean time
      for resumption of oral intake was 2.75 +/- 1.5 days and the length of hospital
      stay was 4.0 +/- 0.8 days. No early recurrences (< 1 yr) have been noted in this
      series. The authors feel that laparoscopic-assisted anterior resection is a safe
      and effective method of treating full-thickness rectal prolapse, thereby avoiding
      a laparotomy and reducing hospital stay.

PMID- 8268504
TI  - Laparoscopic inguinal herniorrhaphy with mesh: an 18-month experience.
AB  - One-hundred-thirty-five laparoscopic inguinal hernia repairs were performed in
      110 patients over an 18 month period. In all, 75 indirect, 24 direct, 23
      bilateral, 5 scrotal, and 7 recurrent hernias were repaired. Types of repairs
      included plug only (4%), plug and patch (19%), and large stapled patch (77%). One
      hundred-six patients were male. No recurrence rates were found at 6 and 12 months
      postoperatively. Minimal postoperative pain was noted in nearly all cases, and
      disability was only 4-10 days in 96% of unilateral repairs. Patients returned to
      immediate unrestricted duties. The operation has evolved from a simple plug
      repair to a large stapled patch. Ninety-seven percent of unilateral repairs were
      performed in less than 80 min. Repair of recurrent hernias created less morbidity
      by avoidance of the old incision. Scrotal hernia repair was expedited by
      amputating the large sac and leaving it in place. Fifty-three percent of patients
      required little or no analgesics. Only four significant complications occurred in
      this series, including an inadvertent bladder injury, one case of persistent pain
      requiring conversion to open repair, one other case of dyspareunia over a plug,
      and one case of uncontrollable bleeding requiring a groin incision. The new
      technique offers minimal incision, minimal pain, and minimal disability.

PMID- 8268505
TI  - Thoracoscopic pleural abrasion for pneumothorax.
AB  - A thoracoscopic pleural abrasion technique is described. Pleural symphysis is
      obtained without thoracotomy. The procedure compliments thoracoscopic bullae
      resection in the management of spontaneous pneumothorax. The thoracoscopic
      abrasion technique is analogous to open pleural abrasion with a scouring pad.

PMID- 8268506
TI  - A technique of laparoscopic gastrectomy and Billroth II gastrojejunostomy.
AB  - This report describes a technique of total intraabdominal laparoscopic
      gastrectomy using laparoscopic stapling and suturing. The reestablishment of
      continuity of the upper gastrointestinal tract was performed by gastrojejunostomy
      (Billroth II) using the Endo GIA stapler. This procedure merits inclusion in the
      armamentarium of approaches toward surgical treatment of recurrent gastric ulcer.

PMID- 8268507
TI  - Laparoscopic subtotal cholecystectomy.
AB  - Subtotal cholecystectomy is a definitive and safe operation to treat diseases of
      the gallbladder, whenever there are major difficulties in dissection from the
      liver. Described herein is successful experience with 6 patients using this
      technique, through the laparoscopic approach. In cases with severe inflammatory
      changes, gallbladder embedded in liver tissue, and liver cirrhosis, they enabled
      reduction of operative time and avoidance of excessive bleeding that could have
      caused the conversion of the laparoscopic approach to open laparotomy.

PMID- 8268508
TI  - Laparoscopic cholecystectomy: the New York experience.

PMID- 8268509
TI  - Outcomes research in laparoscopic surgery: the National Laparoscopic Surgery
      Registry.

PMID- 8268510
TI  - Changes in reimbursement patterns for laparoscopic surgery: experience with
      laparoscopic cholecystectomy.

PMID- 8268511
TI  - Health care coverage for Medicare: cost effectiveness of new technology.

PMID- 8268512
TI  - Assessment of new technology: regulatory agency perspective.

PMID- 8268513
TI  - Current technology assessment programs/procedures.

PMID- 8268514
TI  - The laparoscopic diagnosis and treatment of cavernous hemangioma hemorrhage
      following blunt trauma.
AB  - Cavernous hemangiomas are the most common benign tumor of the liver. A patient
      presented several hours after sustaining blunt trauma to the abdomen. A CT scan
      of the abdomen demonstrated blood in the peritoneal space and several cavernous
      hemangiomas of the liver. Laparoscopy confirmed the liver lesions as the source
      of bleeding, although there was no active blood loss. All intraabdominal blood
      was aspirated and the patient made an uneventful recovery without further blood
      loss. Laparoscopy allowed inspection of the abdomen which revealed cessation of
      intraabdominal hemorrhage from the cavernous hemangiomas. He made a successful
      recovery without further testing or operative intervention.

PMID- 8268515
TI  - Laparoscopic-assisted excision of a solitary cecal ulcer.
AB  - Laparoscopic-assisted excision of a solitary cecal ulcer that presented with
      right lower quadrant pain in a 61-year-old male is described. The patient
      benefited from complete surgical excision of his disease and he experienced a
      rapid postoperative recovery similar to that of other laparoscopic procedures,
      while foregoing the postoperative discomfort and morbidity associated with
      celiotomy. Excision of a complicated, benign cecal ulcer requires minimal bowel
      resection and is particularly amenable to laparoscopic assistance for minimally
      invasive access. For cecal ulcers requiring operative intervention, laparoscopy
      offers an alternative to open celiotomy.

PMID- 8268516
TI  - Laparoscopic placement of a percutaneous endoscopic gastrostomy (PEG) feeding
      tube.
AB  - Patients may have abnormal anatomic relationships between the stomach and
      adjacent organs, particularly when there is a history of abdominal surgery and
      adhesion formation. Routine placement of a percutaneous endoscopic gastrostomy
      tube can then be unsafe and result in inadvertent colon perforation, small bowel
      enterotomy, or injury to other structures. Described herein is a 94-year-old
      malnourished male in whom the colon lay directly anterior to the greater
      curvature of the stomach. A new technique was devised--laparoscopically-directed
      PEG placement--which proved to be a safer alternative approach in this patient.

PMID- 8268517
TI  - Microfibrillar collagen hemostat during laparoscopically directed liver biopsy.
AB  - Meticulous hemostasis is a necessity during laparoscopic procedures in
      maintaining a clear visual field and avoiding the need for an extended laparotomy
      to secure hemostasis. Methods of hemostasis available to laparoscopic surgeons
      include direct pressure, suture/clip ligation, conventional monopolar or argon
      enhanced coagulation, and application of topical hemostatic agents. The
      effectiveness of topical hemostatic agents for open surgical procedures has been
      demonstrated; however, to date, laparoscopic utilization of topical hemostatic
      agents has been hampered by lack of compatible forms for laparoscopic
      instillation. Endo-Avitene is a 15 x 50 mm rolled sheet of microfibrillar
      collagen hemostat, available in an applicator capable of placement through
      standard laparoscopic trocar. The use of Endo-Avitene during laparoscopically
      directed liver biopsies in a porcine model is reported. The effective hemostatic
      properties of microfibrillar collagen hemostat were reaffirmed and the clinical
      utility of Endo-Avitene for laparoscopic use is demonstrated.

PMID- 8268518
TI  - Small bowel obstruction due to Richter's hernia after laparoscopic procedures.
AB  - Two cases of a Richter's hernia through the trocar site after laparoscopic
      procedures are presented. A discussion of the etiology and prevention of this
      complication are also presented.

PMID- 8268519
TI  - The lost needle: a laparoscopic dilemma.
AB  - A case is presented in which a curved needle became lost during extracorporeal
      suturing in laparoscopic surgery. Maneuvers to find the needle were fruitless
      until an intraoperative x-ray showed it was stuck in the flapper mechanism of a
      laparoscopic cannula. Caution is given against the use of "pop-off" needles
      during extracorporeal suturing and an x-ray of cannulae is suggested when a lost
      needle cannot be found using routine maneuvers.

PMID- 8268520
TI  - The role of ERCP and therapeutic biliary endoscopy in laparoscopic
      cholecystectomy.

PMID- 8268521
TI  - My life with ASAIO.

PMID- 8268522
TI  - Continuing development of the Cleveland Clinic-Nimbus total artificial heart.
AB  - A completely implanted total artificial heart (TAH) is under development by
      Nimbus, Inc., and the Cleveland Clinic Foundation (CCF). Key features of the
      system include an electrohydraulic energy converter, an automatic control system
      that produces a Frank-Starling response, and dual ventricles composed of graphite
      epoxy and titanium with gelatin blood contacting surfaces. The system is
      controlled by a single substrate, hybridized microcircuit (the hybrid).
      Fabrication of the TAH control hybrid has recently been completed and testing
      begun. Its design emphasizes simplicity, reliability, and efficiency. Particular
      attention was given to optimizing thermal management. Externally controlled TAH
      systems have been used in eight in vivo experiments of up to 120 days' duration.
      In the last two of these experiments, a variable volume device was also implanted
      with excellent results. In vivo use of the system has demonstrated the Frank
      Starling pump response, but the systems quickly reach maximum output with the
      bovine animal models. Human fitting studies, including adult patients undergoing
      heart transplantation, demonstrated satisfactory fit of the pump within the
      pericardium without compression of the vascular structures or chest wall.
      Measurements of chest circumference, plain chest films, and transesophageal
      echocardiograms should provide reliable predictions of pump fit in the majority
      of patients.

PMID- 8268523
TI  - The Baylor-ABI electromechanical total artificial heart. Accelerated endurance
      testing.
AB  - To test the durability of each part or assembled component of the Baylor-ABI
      total artificial heart (TAH), the authors performed an endurance test under
      severe conditions. The TAH was immersed in a saline bath at 42 degrees C, which
      is 4-5 degrees C higher than normal body temperature. This is an accelerated
      endurance test because of the elevated temperatures. In this accelerated
      endurance test loop, the 42 degrees C heated saline was circulated not only in
      the pump but also outside the pump. During pumping, temperatures of the motor and
      outside surface of the centerpiece were continuously measured. This testing
      showed that during almost 4 months of pumping no electromechanical troubles were
      observed. Both inside (motor) and outside temperatures were stable and the
      differences in both temperatures were only 3-4 degrees C, demonstrating that heat
      generation is not a problem. The voltage and current required in this system
      remained constant, indicating stable and reliable performance. Based on these
      results, this pump is expected to run continuously over a long duration in a
      normal physiologic environment. This accelerated endurance test system is very
      suitable for estimating the influence of heat generation by the actuator of blood
      pumps. It is also quite useful in validating the durability of various cardiac
      prosthesis.

PMID- 8268524
TI  - In vivo testing of a completely implanted total artificial heart system.
AB  - The authors performed 14 implants of a completely implanted total artificial
      heart (TAH) system in calves. The system consisted of a dual pusher plate
      rollerscrew energy converter, two sac type blood pumps, an implanted electronic
      control and battery package, and a transcutaneous energy transmission system. Ten
      of the implants included a percutaneous lead for monitoring of the implant; the
      remainder made use of wireless two way telemetry between the implant and the
      outside. Three animals survived the perioperative period. These calves survived
      for 98 to 118 days, and one was still alive at 150 days. Causes for termination
      of the 98 and 118 day cases were abdominal pocket sepsis originating at a
      monitoring line, and systemic sepsis acquired perioperatively. Death or
      termination in the shorter cases was mainly due to respiratory complications or
      bleeding. The TAH system proved capable of providing adequate cardiac outputs at
      modest atrial pressures. Wireless monitoring and wireless intervention for
      weaning from cardiopulmonary bypass were readily achieved. All organ systems
      functioned normally in the presence of the device. Once recovery from
      implantation in these very young animals was achieved, the system proved its
      ability to reliably support these animals until body mass exceeded its cardiac
      output capabilities.

PMID- 8268525
TI  - Tranexamic acid reduces blood loss after cardiopulmonary bypass.
AB  - To evaluate the effect of tranexamic acid (TA) on blood loss after
      cardiopulmonary bypass (CPB), 157 patients who underwent elective valve
      replacement operations were studied, with one group of 90 patients receiving
      tranexamic acid (Group TA) and 67 patients serving as the control group (Group
      N). In group TA, 50 mg/kg of tranexamic acid was administered just before and
      after CPB, and every 90 minutes during CPB. The activated coagulation time was
      maintained at more than 450 seconds during CPB in both groups. There was no
      significant difference in the CPB time between the groups (163 +/- 32 min in
      group N and 152 +/- 38 min in group TA:NS). The time required for hemostasis was
      shortened in group TA, which resulted in a shorter operation time (6.7 +/- 1.5
      hrs vs 6.0 +/- 1.5 hrs in group N and group TA, respectively: p = 0.006). The
      amount of chest tube drainage within 12 hours after surgery was significantly
      reduced (225 +/- 129 ml vs. 180 +/- 118 ml in group N and group TA, respectively:
      p = 0.026). The chest tube was able to be removed earlier in group TA, and the
      total blood loss was significantly smaller in group TA (402 +/- 292 ml) than in
      group N (631 +/- 609 ml; p = 0.004). The authors thus conclude that
      antifibrinolytic therapy during CPB with tranexamic acid reduces postoperative
      blood loss, and shortens the operation time due to an improvement in hemostasis.

PMID- 8268526
TI  - Can protamine be used during perfusion with heparin surface coated equipment?
AB  - Left heart bypass (LHBP) with heparin coated perfusion equipment including an
      arterial filter (pore size: 40 microns) was performed in five canine experiments
      after full systemic heparinization (heparin 300 IU/kg; activated coagulation time
      [ACT] > 480 sec). The heparin coated filter was replaced after 45 min with a
      second heparin coated filter. Protamine (1:1) was added after 45 min and
      perfusion was continued for another 45 min before the second filter was replaced
      with an uncoated control filter. In addition to continuous hemodynamic
      monitoring, all filters were disassembled and analyzed morphometrically with a
      scanning electron microscope (deposits on screens were expressed as percent of
      surface covered with fibrin or number of cells/100 micron 2, respectively). For
      the first heparin coated filter (ACT > 480), 0.3 +/- 0.5% of the surface was
      covered with fibrin, 0.7 +/- 0.7% with platelets, and 0.02 +/- 0.0% with red
      cells. For the second heparin coated filter exposed to neutralization of heparin
      with protamine, surface coverage was fibrin in 22 +/- 15%, platelets in 3.2 +/-
      0.8%, and red cells in 0.2 +/- 0.1% (p < 0.05 for all comparisons with filter 1).
      For uncoated control filters (ACT = 120), surface coverage was fibrin in 31 +/-
      33%, platelets in 3.7 +/- 2.9%, and red cells in 0.2 +/- 0.1% (not significant
      [NS] for all comparisons with filter 2). Although all arterial filters used in
      this study remained patent throughout the scheduled period, it became clear that
      protamine given during perfusion reduces the antithrombotic activity of bonded
      heparin. Hence, protaminization during perfusion with heparin coated equipment
      cannot be recommended.

PMID- 8268527
TI  - A novel electrochemical heparin sensor.
AB  - Heparin is one of the most important clinical drugs, and is employed universally
      during surgical procedures and extra-corporeal therapies to prevent blood from
      clotting. Its clinical use, however, is often associated with serious hemorrhagic
      complications. Because of this life threatening bleeding risk, there is a need
      for a simple sensing device that can rapidly and directly monitor heparin levels
      during extra-corporeal therapies to provide a safeguard during these procedures.
      Current heparin assays are all based on the measurement of blood clotting time,
      and none of them are suitable for direct and rapid determination of heparin. We
      describe applying conventional ion selective electrode (ISE) polymer membrane
      technology and using a specifically formulated membrane doped with
      tridodecylmethylammonium chloride (TDMAC) as the heparin complexing agent, to
      devise the first electrochemical sensor for heparin measurement. The sensor is
      capable of detecting directly and rather selectively the free heparin
      concentrations in both physiologic saline and undiluted plasma samples. In
      addition, the clinical utility of the sensor has been demonstrated by monitoring
      the levels of heparin in undiluted whole blood specimens obtained from patients
      undergoing open heart operations. It is envisioned that the sensor could be
      configured as an in-line device within extracorporeal blood loops to monitor
      current extracorporeal therapy, or as a convenient single use disposable device
      for rapid bedside or laboratory measurements of heparin in small discrete samples
      of undiluted whole blood. Preliminary studies concerning the feasibility of
      designing a mass fabricated, solid state, disposable heparin sensor also have
      been conducted.

PMID- 8268528
TI  - Selective cerebral perfusion in patients with aortic aneurysms involving the
      aortic arch.
AB  - Patients with aortic arch aneurysms underwent surgery using a selective cerebral
      perfusion (SCP) method. For this purpose, a protocol for SCP was established on
      the basis of an animal experimental study. Our SCP procedure is performed at a
      perfusion rate of 6 ml/kg/min with the patient under deep hypothermia at 20
      degrees C. The subject group in the current study included 36 patients, 28 men
      and eight women, ranging in age from 23 to 84 years (mean, 61). There were five
      operative deaths (13.9%). The mean cardiopulmonary bypass time was 288 minutes,
      and the mean aortic clamp time was 135 minutes. Mean SCP time was 89 minutes,
      exceeding 90 minutes in 17 cases. The mean blood pressure during SCP was 43 mmHg
      and oxygen saturation rate in the internal jugular vein was at least 90%. There
      was no definite production of lactate in the brain. Cerebral disorders considered
      to have been caused by SCP occurred in only two cases. It appears that cerebral
      metabolism can be maintained safely, and that our SCP method is useful during
      surgery for aortic arch aneurysms.

PMID- 8268529
TI  - A disposable heart-lung machine. Results of animal testing.
AB  - A small wave propagation pump (WPP) was incorporated into oxygenators to create a
      disposable heart-lung machine. The WPP provides undirectional micropulsatile
      laminar flow of 8 L/min against 800 mmHg. The smaller WPP can generate 4 L/min
      against 400 mmHg (cardioplegia), or reversed, and can create up to 150 mmHg
      negative pressure for suction. Power needs were 110 volts and 0.5 amps or 24
      volts DC and 1.5 amps. The WPP is self priming (20 cc) and de-aired in less than
      3 min. Seven dogs (average weight, 36 kg) were supported for 3 hrs. Flows could
      accurately be adjusted from 0.005 to 8 L/min. Flow through the oxygenator and
      perfusion circuit averaged 3.1 L/min (2.0 to 4 L/min). Serial analysis of blood
      samples showed minimal hemolysis and no significant change in hematocrit,
      hemoglobin, white blood count, red blood count, or platelet count (p > 0.01). The
      inexpensive WPP oxygenator combination function as a disposable heart-lung
      machine.

PMID- 8268530
TI  - In vivo performance evaluation of a transcutaneous energy and information
      transmission system for the total artificial heart.
AB  - As part of an electromechanical total artificial heart (TAH) program, an
      integrated transcutaneous energy and information transmission (TEIT) system has
      been developed. In vivo performance of the developed system was evaluated through
      a simplified animal model without implant of a TAH. The design features include
      the small size of the implanted part, and dual coil structure of the external
      part. In the transcutaneous energy transmission (TET) system based on magnetic
      induction, the external primary and implanted secondary coils have the shape of a
      truncated cone, 7.0 and 3.8 cm in diameter, and 23 and 12 turns of Litz wire,
      respectively. The external coil is driven by a 350 to 410 kHz tuned class E
      amplifier that has a minimum switching loss of power transistor. In vitro test
      results using 1 cm thick dog's skin showed a flat total efficiency (DC to DC) of
      75% for 20 to 30 W of delivered mean power. In order to achieve bidirectional
      communication between implanted and external components, a small circuit board
      containing four light emitting diodes and a photodiode was incorporated in each
      TET coil facing each other across the skin. Unmodulated optical pulse transmitted
      digital data (9600 baud, RS-232 protocol) in error free condition through an up
      to 15 mm thick dog's skin patch accommodated 18 degrees of misalignment. Three
      subacute in vivo studies were conducted in dogs to evaluate performance of the
      developed system. The secondary set was implanted in the mild flank region of the
      dog, and the output was percutaneously connected to the control system to drive
      the external TAH on the mock circulatory system.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268531
TI  - An atrial hydraulic shunt in a total artificial heart. A balance mechanism for
      the bronchial shunt.
AB  - An implantable TAH must be able to maintain physiologic atrial pressures over a
      range of left side shunt flows, which in humans can range up to 5% of the total
      cardiac output (CO). The authors describe the characteristics of an atrial
      hydraulic shunt in an electrohydraulic TAH. A small (10 cc stroke) chamber placed
      in line between the left atrial cuff and the inflow valve is shunted to the right
      hydraulic chamber. High left atrial pressure increases the volume displaced by
      this chamber; this concurrently reduces the right chamber stroke volume and flow
      relative to the left side. For left atrial pressures (LAP) between 0 and 15 mmHg,
      CO increased from approximately 3 to > 9 L/min (Starling-like behavior). This was
      attainable with bronchial flow settings between 0.2 to 0.7 L/min, satisfying
      physiologic needs. Left atrial pressure and RAP (right atrial pressure) tracked
      each other. The mean difference, LAP-RAP, remained within 5 mmHg at low filling
      pressures and approached 0 mmHg difference at high filling pressures. The results
      showed that the atrial hydraulic shunt method can adequately compensate for and
      manage physiologic left-right flow differences.

PMID- 8268532
TI  - The Sternotomy Hemopump. A second generation intraarterial ventricular assist
      device.
AB  - The first generation Hemopump is a VAD based on a catheter mounted intraarterial
      axial flow blood pump that is placed through the femoral artery. Blood is
      withdrawn from the left ventricle through a transvalvular inflow cannula and
      pumped into the aorta. Clinical trials have demonstrated hemodynamic efficacy,
      improved survival, and low hemolysis in cardiogenic shock. The incidence of non
      insertion of the device and fracture of the flexible drive cable limited its
      utility, however. In addition, some processes used in pilot production could not
      be adapted to volume manufacturing. A second generation device, the Sternotomy
      Hemopump, has been developed for insertion through the ascending aorta. Design
      changes include a shortened inflow cannula, higher flow hydraulics, and a more
      durable flexible drive cable. In addition, more efficient manufacturing processes
      were implemented. In a pulsatile mock loop the flow was 5.7 L/min at 100 mmHg. In
      vivo experiments of up to 2 weeks demonstrated a mean plasma free hemoglobin of
      8.7 mg/dl, minimal valve injury, and an acceptable incidence of renal infarction.
      In vitro endurance demonstrated a 7 day reliability of 99.9% with a 95%
      confidence. A new clinical trial will evaluate the use of the Sternotomy Hemopump
      for nonoxygenator support during aorto-coronary artery bypass surgery.

PMID- 8268533
TI  - Development of a miniature intraventricular axial flow blood pump.
AB  - A new intraventricular axial flow blood pump has been designed and developed as a
      totally implantable left ventricular assist device (LVAD). This pump consists of
      an impeller combined with a guide-vane, a tube housing, and a DC motor. The pump
      is introduced into the LV cavity through the LV apex, and the outlet cannula is
      passed antegrade across the aortic valve. Blood is withdrawn from the LV through
      the inlet ports at the pump base, and discharged to the ascending aorta. Our
      newly developed axial flow pump system has the following advantages: 1) it is a
      simple and compact system, 2) minimal blood stasis both in the device and the LV
      cavity, 3) minimal blood contacting surface of the pump, 4) easy accessibility
      with a less invasive surgical procedure, and 5) low cost. A pump flow > 5 L/min
      was obtained against 100 mmHg differential pressure in the mock circulatory
      system. The pump could produce a passive pulsatile flow effect with a beating
      heart more efficiently than other non-pulsatile pumps because of minimal pressure
      drop and inertia along the bypass tract. Anatomic fit studies using dissected
      hearts of dilated cardiomyopathy (DCM) cadavers showed that this pump could
      smoothly pass through the aortic valve without any interference with mitral valve
      function. Recently, a dynamic pressure groove bearing and a miniature lip seal
      have been developed. The dynamic pressure groove bearing has a simple structure
      and acts as a pressure resistant sealing mechanism.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268534
TI  - In vivo evaluation of the Nimbus axial flow ventricular assist system. Criteria
      and methods.
AB  - Continuing in vivo trials are being conducted at the University of Pittsburgh
      using the Nimbus axial flow blood pump (AxiPump). To date, 14 sheep experiments
      have been performed to address several issues related to short-term support. Six
      acute experiments (< 6 hr) have been performed to assess hemodynamics related to
      speed regulation and to determine anatomic placement of the pump and cannulae.
      Eight short-term survival studies lasting up to 6 days have been performed to
      evaluate biocompatibility and system reliability, and to establish clinical
      management protocols. The AxiPump has been used as a left ventricular assist
      device (LVAD), right ventricular assist device (RVAD), and biventricular assist
      device (BiVAD) with left ventricular and right atrial cannulation. The AxiPump
      has demonstrated the ability to assume complete support of either the pulmonary
      or systemic circulation, or both. We have determined that sufficient surgical
      access may be obtained through left lateral thoracotomy for both LVAD and RVAD
      insertion. In the absence of post operative anticoagulation therapy, we have
      detected subclinical renal cortical infarctions in 6 of 8 short-term animals.
      Thrombus deposition has been observed at the ventricular cannula tip in 4 of 8
      cases--necessitating design changes. Two short-term experiments have been
      terminated because of bleeding--one due to inflow cannula obstruction and one due
      to cannula failure. Plasma free hemoglobin levels were all below 15 mg/dl, except
      for one case complicated by inflow obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268535
TI  - Control of a rotary pulsatile cardiac assist pump driven by an electric motor
      without a pressure sensor to avoid collapse of the pump inlet.
AB  - Our ventricular assist device uses a valveless volumetric pump operating on the
      Maillard-Wankel rotary principle. It is driven by an electric motor and provides
      a semi pulsatile flow. At each cycle, blood is actively aspirated into the
      device, and overpumping results in collapse at the pump inlet. To prevent
      overpumping, it is necessary to ensure that pump intake does not exceed venous
      return. Poor long-term reliability rules out the use of current implantable
      pressure sensors for this purpose. To resolve this problem, we have developed a
      method of control based on monitoring of the intensity of electric current
      consumed by the motor. The method consists of real time monitoring of current
      intensity at the beginning of each pump cycle. A sudden change in intensity
      indicates underfilling, and motor speed is reduced to prevent collapse. The
      current consumed by the motor also depends on the afterload, but the form of the
      signal remains the same when afterload changes. After demonstrating the
      feasibility of this technique in a simulator, we are now testing it in animals.
      We were able to detect and prevent collapse due to overpumping by the cardiac
      assist device. This system also enables us to know the maximum possible
      assistance and to thus adapt assistance to the user.

PMID- 8268537
TI  - Relationship between insulin secretion and oxygen tension in hybrid diffusion
      chambers.
AB  - Oxygen tension is of potential importance in hybrid diffusion chambers, where
      both islet density and the site chosen for implantation can significantly affect
      the pO2 within the chambers. To investigate this, isolated islets were incubated
      at oxygen tensions of 38 mmHg ("low") and 154 mmHg ("ambient"). The mean (+/- SD)
      ratio between insulin secretion at low and at ambient oxygen tensions was 0.92 +/
      0.27 (n = 10) for porcine islets and 0.80 +/- 0.08 (n = 5) for canine islets.
      The pO2 was then determined in vivo in cylindrical diffusion chambers (inner
      diameter 4.5 mm) fabricated from acrylic copolymer, seeded with isolated porcine
      islets at densities of 0, 15, 30, and 45 islets/mm3, and implanted
      intraperitoneally in rats. The pO2 levels inside the chambers after 2 weeks were
      57 +/- 6 (n = 12), 39 +/- 5 (n = 6), 38 +/- 6 (n = 6), and 43 +/- 3 (n = 6) mmHg,
      respectively. After 6 weeks, the results were 51 +/- 3 (n = 6), 26 +/- 8 (n = 3),
      29 +/- 12 (n = 3), and 40 +/- 5 (n = 3) mmHg, respectively. In comparison,
      similar chambers containing 10 islets/mm3 cultured for 1 week at ambient oxygen
      had a pO2 of 120 +/- 9 (n = 4) mmHg immediately underneath the membrane and 67 +/
      7 (n = 4) mmHg at the axial center.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268536
TI  - Immunologic considerations in the use of cultured porcine hepatocytes as a hybrid
      artificial liver. Anti-porcine hepatocyte human serum.
AB  - Cultured porcine hepatocytes with reasonable metabolic functions are a promising
      bioreactor for a hybrid artificial liver in the treatment of liver failure. A
      cytotoxic human serum (t-serum) against cultured porcine hepatocytes was
      accidentally discovered during preliminary experiments, however, which prompted
      the authors to study the mechanism of the cytotoxicity and the frequency of
      occurrence of the cytotoxic sera. Among 103 individual sera examined, seven
      (6.8%) sera showed cytotoxicity to cultured porcine hepatocytes. T-serum heated
      at 56 degrees C for 30 min completely lost its cytotoxic activity, but the
      inactivated cytotoxicity was restored by the addition of rabbit complement to the
      inactivated t-serum. IgM-depleted t-serum produced by 2-mercaptoethanol treatment
      abolished the cytotoxicity to porcine hepatocytes. The cytotoxic reactions were
      therefore thought to be mediated by IgM capable of complement activation.
      Although IgM binding to porcine hepatocytes was also seen in nontoxic sera, the
      IgM did not activate complement. This implies differences in hepatocyte surface
      antigens recognized by IgM from t- and nontoxic sera. Before clinical application
      of a hybrid artificial liver using cultured porcine hepatocytes, detection of
      cytotoxic human IgM against porcine hepatocytes is necessary, and the means of
      eliminating the cytotoxic IgM from the hybrid artificial liver system, or of
      inactivating complement in the system, will be desirable in cases positive for
      cytotoxic IgM.

PMID- 8268538
TI  - Pharmacokinetic analysis verifies P450 function during in vitro and in vivo
      application of a bioartificial liver.
AB  - Lidocaine is a sensitive substrate for evaluating liver P450 function. In this
      study, metabolism of lidocaine by xenogeneic hepatocytes in a hollow fiber,
      bioartificial liver was measured under in vitro conditions (n = 6) and in an
      anhepatic rabbit model. Animals in the treatment group (n = 6) received
      hemoperfusion by a bioartificial liver that contained 100 million rat
      hepatocytes. Other anhepatic rabbits received no hemoperfusion (n = 3) or a
      bioartificial liver with no cells (n = 3). Lidocaine clearance was 7.0 +/- 0.6
      ml/min, and the half-life of lidocaine was 5.6 +/- 0.8 hr under in vitro
      conditions. Conversion of lidocaine to 3-hydroxy-lidocaine was confirmed in vitro
      and accounted for 46% of lidocaine elimination in the hepatocyte bioartificial
      liver. During in vivo application of the bioartificial liver, pharmacokinetic
      parameters of lidocaine metabolism, including drug half-life and metabolite
      formation, were significantly improved in anhepatic rabbits. 3-Hydroxy-lidocaine
      profiles verified the activity of a P450 isozyme expressed preferentially by rat
      hepatocytes in the bioartificial liver. We conclude that hepatic P450 activity
      was provided by xenogeneic hepatocytes during in vitro and in vivo applications
      of a bioartificial liver.

PMID- 8268539
TI  - Design concept and construction of a hybrid lamellar keratoprosthesis.
AB  - A novel hybrid lamellar keratoprosthesis composed of epithelium and stroma was
      developed. Artificial extracellular matrices were constituted of
      photocrosslinkable copolymers of N,N-dimethylacrylamide and 2-(7-coumaroxy)ethyl
      methacrylate; a copolymer with a high content of coumarin (A) was used as a
      basement membrane (BM) for the epithelium, and a copolymer with a low content (B)
      was used for entrapment of keratocytes. The lamellar keratoprosthesis was
      constructed as follows: First, a viscous buffer solution containing water-soluble
      copolymer (B), collagen, and keratocytes derived from rabbit was prepared. Then,
      a cast film of copolymer (A) was tightly placed onto the mixed solution.
      Ultraviolet light irradiation leading to intermolecular dimerization of coumarin
      groups resulted in the formation of a transparent keratocyte-entrapped hydrogel
      that was layered with an artificial BM. Epithelial cells were seeded on the BM.
      Further culturing produced the lamellar keratoprosthesis, within which both kinds
      of cells proliferated well. The preliminary study on two week implantation of the
      lamellar keratoprosthesis in rabbits provided quite promising results; adverse
      tissue reactions, such as corneal opacity and neovascularization, were not
      observed.

PMID- 8268540
TI  - Development of a hybrid artificial pancreas with a dense polyurethane membrane.
AB  - We have synthesized a series of strong, elastomeric polyurethaneureas and have
      used them to fabricate non-porous film and hollow fiber membranes. The solvent
      cast membranes are non cytotoxic, angiogenic, and permeable to gases, nutrients,
      secretagogues, and cell products via purely concentration driven transport.
      Permeability to water, glucose, and protein increases monotonically with membrane
      water absorption above a threshold value. Water absorption increases with soft
      segment hydrophilicity, soft segment molecular weight, and soft segment volume
      fraction of the (dry) segmented polyurethanes. Cell lines (RAJI and MOPC-31C) and
      primary cells (porcine islets) contained within our membranes have been
      maintained in culture for up to 6 months with nutrients supplied only by the
      external media. Cells within membrane devices were protected from immune
      rejection when implanted into murine hosts. Simple, compact devices containing
      porcine islets restored normoglycemia and near normal response to glucose
      tolerance tests in diabetic mice for at least 2 months. Explants had a high
      degree of vascularization adjacent to the membrane, with little or no fibrous
      tissue. These properties, and the material's ability to support cell function and
      protect xenogeneic cells from immunologic rejection, suggest that it would be
      useful in the construction of hybrid artificial organs and in in vitro cell
      culture.

PMID- 8268542
TI  - Development of a hierarchically structured hybrid vascular graft biomimicking
      natural arteries.
AB  - A hierarchically structured hybrid vascular graft, resembling the layered
      structure of the intima and the media of a natural artery, is expected to exhibit
      structural stability and function similar to those of an artery. Two models of
      hybrid vascular grafts were constructed on knitted Dacron grafts (internal
      diameter, 4 mm; length, 6 cm; Golaski Laboratories, Inc., Philadelphia, PA) in
      vitro. The model I graft consisted of only an endothelial cell (EC) monolayer,
      and the model II graft was hierarchically structured with an EC monolayer and
      smooth muscle cell (SMC) multilayers embedded in a mixed gel of type I collagen
      and dermatan sulfate. Both models were implanted bilaterally in carotid arteries
      of 11 dogs for up to 12 weeks without anticoagulant. All grafts were patent after
      the implantation. There was a marked difference in the formation of the neomedia
      between the two models at 2 weeks: only a collagenous layer was observed beneath
      the EC monolayer in model I grafts, whereas the reconstructed neomedia consisting
      of proliferating SMCs and extracellular matrix was observed in model II grafts.
      In model I grafts at 2 weeks, the luminal surface with a wavelike form, along
      with crimps of the vascular graft, was almost endothelialized, but EC orientation
      was disorganized at the troughs of the crimps. Leukocyte adhesion on ECs and
      migration into their interstices were observed in some areas. Such events were
      infrequent in model II grafts at 2 weeks. Model II grafts at 12 weeks had an
      integrated neomedia comparable to that of a natural artery: SMCs exhibited dense
      accumulation and circumferential orientation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268541
TI  - Noninvasive quantification of platelet accumulation and release on indwelling
      venous catheters.
AB  - An important element in the evaluation of biomaterials is quantification of the
      relationships and the sequence of events between blood elements, blood flow, and
      the foreign surface. We adapted a qualitative two-dimensional 111In-labeled
      platelet imaging method to a quantitative noninvasive analysis of platelet
      uptake/release kinetics for infusion catheters in a canine model. Bilateral
      femoral vein 6 Fr. Groshong catheters (one treated with a hydroxylated siloxane
      to improve albumin affinity) were monitored at femoral vein sites with a GE 400T
      gamma camera, interfaced with a Technicare 560 image acquisition computer. The
      field of view was sufficiently large that all events below the diaphragm were
      recorded without having to move the camera. Image acquisition time was 2.5 min;
      images were obtained every 5-15 min for 3 hrs. Continuous recordings were
      obtained from bilateral ultrasonic velocity probes, attached distal to the
      catheter implant sites. A 5 ml blood sample was placed in the field to permit
      calibration of gamma emissions per pixel in terms of labeled platelet density.
      Signal compensation for near field capillary perfusion was performed. The two
      dimensional platelet distribution was computed and displayed. Local, time
      dependent platelet accumulation on the catheters and adjacent vessel walls was
      observed. Platelet accumulation proceeded in irregular steps during the implant
      period. Loss of local platelet deposits was observed. Downstream reattachment of
      platelet emboli was inferred from simultaneous reductions and increases in local
      platelet densities at two catheter positions. Platelet attachment was inversely
      related to vein blood velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268543
TI  - Phenotypic modulation of smooth muscle cells in intima-media incorporated hybrid
      vascular prostheses.
AB  - Hierarchical hybrid vascular grafts were constructed with an endothelial cell
      (EC) monolayer and hybrid medial layer composed of smooth muscle cells (SMCs) and
      type I collagen gel. The grafts, implanted into canine carotid arteries for up to
      12 weeks, were ultrastructurally examined with a transmission electron
      microscope. Before implantation, SMCs incorporated into hybrid media were round
      and intracellularly filled with synthetic organelles such as rough endoplasmic
      reticula, mitochondria, free ribosomes, and Golgi complexes. Two weeks after
      implantation, bipolar spindle shaped SMCs still remained in a synthetic
      phenotype. At 12 weeks, circumferentially aligned SMCs were abundant in
      contractile apparatus such as myofilaments, dense bodies, and basement membranes.
      In a morphometric evaluation, the populations of three phenotypic SMCs
      (synthetic, intermediate, and contractile SMCs) were quantified. At 2 weeks, the
      proportions were 50.5, 41.8, and 7.7% for synthetic, intermediate, and
      contractile phenotypes, respectively. At 12 weeks, they were 9.9, 26.2, and
      63.8%. These findings indicated that SMCs incorporated into hybrid grafts were
      transformed from a synthetic to a contractile phenotype under pulsatile stressed
      conditions after 12 weeks in vivo. Thus, the intima/media incorporated hybrid
      graft reconstructed a vessel wall similar to a native one in terms of structure
      and function.

PMID- 8268544
TI  - Development of a magnetically operated artificial urethral sphincter. Chronic
      effects of compression on the skin structure and blood flow.
AB  - The artificial urethral sphincter (AUS) has been in clinical use for more than 20
      years. Currently available AUS devices, however, are difficult to use and not
      entirely reliable. A magnetically operated AUS is currently under the
      development. Although the skin between the magnets will be compressed all day
      long, little information exists on the effects of chronic pressure on the skin
      structure and blood flow. In five miniature pigs, two internal magnets and one
      control metal disk were implanted subcutaneously at three different positions,
      and external magnets with differing magnetic forces were applied to the skin
      overlying the internal magnets for six weeks. In four pigs, the skin blood flow
      was measured by a laser Doppler flow meter applying different pressures.
      Compression of 10 mmHg preserved normal skin morphology in all but one animal
      where blood flow had not recovered 2 weeks after surgery. Compression of 20 mmHg
      for 6 weeks, however, produced pressure ulcers in all five cases (p < 0.05 vs. 10
      mmHg group). The skin blood flow declined for pressures exceeding 20 mmHg (0
      mmHg: 4.3 +/- 1.2, 10 mmHg: 4.3 +/- 3.3, 20 mmHg: 2.6 +/- 2.7 ml/min/100 g). We
      concluded that the magnetically operated AUS should use a magnetic coupling with
      a pressure less than 10 mmHg exerted on the interposing skin.

PMID- 8268545
TI  - Anaphylactoid reactions and bradykinin generation in patients treated with LDL
      apheresis and an ACE inhibitor.
AB  - An anaphylactoid reaction was observed in a patient treated with low density
      lipoprotein (LDL) apheresis using a dextran sulfate cellulose (DSC) column and
      administration of an angiotensin converting enzyme (ACE) inhibitor. The authors
      have investigated to determine the causes and countermeasures. When using heparin
      as the anticoagulant, large increases in bradykinin levels in plasma were
      observed after its passage through the column during the procedure. Increase in
      bradykinin levels in blood were observed, to a lesser but still significant
      degree, after terminating the procedure. When withholding the ACE inhibitor for a
      few days before LDL-apheresis, the increase in bradykinin levels was much
      weakened and the anaphylactoid reactions became mild. Such anaphylactoid
      reactions were not observed when the ACE inhibitor was withheld for a few weeks,
      or when using Futhan instead of heparin as the anticoagulant. Although the
      critical level of bradykinin needed to cause the anaphylactoid reaction and the
      other possible causal factors remained unclear, the bradykinin levels are thought
      to be related to the reactions.

PMID- 8268546
TI  - Low density lipoprotein apheresis during cardiopulmonary bypass of
      hypercholesterolemic patients.
AB  - Ischemia-reperfusion injury in open heart surgery can cause atherosclerotic
      changes in both bypass grafts and native coronary arteries by increasing
      endothelial permeability and allowing excessive influx of LDL into the
      subendothelium. The authors used LDL apheresis during cardiopulmonary bypass
      (CPB) to actively remove serum LDL before reperfusion, minimizing LDL influx.
      They evaluated the efficacy and safety of this new procedure in eight
      hypercholesterolemic patients. The control group consisted of 41 patients. Mean
      LDL cholesterol (LDL-C) level on admission was 180 +/- 41 (SD) in the LA group
      and 139 +/- 32 mg/dl in the control group (p = 0.02). After 105 +/- 27 min of
      apheresis, the LDL-C level in the LA group decreased to 62 +/- 25 mg/dl
      (reduction rate: 59 +/- 18%). In contrast, in the control group, the LDL-C level
      was reduced to 117 +/- 41 mg/dl (reduction rate: 16 +/- 9.5% [P = 0.0001]) after
      CPB. No significant difference was observed in intraoperative blood loss,
      postoperative blood loss, platelet count, prothrombin time, activated partial
      thromboplastin time, incidence of wound complications, or early patency rate of
      bypass graft between groups. Low density lipoprotein apheresis during CPB is a
      safe and effective method for lowering serum LDL level sufficiently before
      reperfusion, and can adequately reduce LDL influx into the vessel wall.

PMID- 8268547
TI  - Zeta potential of hollow fiber dialysis membranes and its effects on hydrogen
      phosphate ion permeability.
AB  - To clarify ion transport, dialysis membranes are evaluated in terms of zeta
      potential calculated by the Helmholtz-Smoluchowski equation from data on
      streaming potential delta E and pressure drop delta P, depending upon the
      operating conditions at which the values are measured. The objective of the
      current study is to design an improved method for measurement of delta E and
      delta P of hollow fiber dialysis membranes and to clarify the diffusive
      permeability of hydrogen phosphate ion. A polytetrafluoroethylene cylindrical
      cell with an inside diameter of 14 mm and a height of 10 mm was packed with 2,000
      3,000 pieces of hollow fibers, and glass filters were set on either side of the
      cell. Deaerated water purified by ion exchange and reverse osmosis with an
      electric conductivity of approximately 150 microS/m was caused to flow in the
      hollows at 293 K to determine delta E and delta P. A good linear relationship
      between delta E and delta P and the reproducibility of the data was obtained and
      is shown in Figures 5 and 6, demonstrating the utility of the improved method to
      measure delta E and delta P, and the validity of the Helmholtz-Smoluchowski
      equation to calculate zeta potential from data on delta E and delta P. Hydrogen
      phosphate ion permeability increased with zeta potential for the membranes at
      about the same rate as pure water permeability. This indicates that hydrogen
      phosphate ion permeability depends upon the charge and internal structure of
      dialysis membranes.

PMID- 8268548
TI  - Pulsed plasma discharge polymer coatings.
AB  - The authors studied a pulsed radiofrequency glow discharge polymer film
      deposition method (pRFGD) on polyethylene terephthalate (PET), silicon (Si), and
      potassium chloride (KCl) surfaces, with the aim of better controlling film
      uniformity and homogeneity. A pulse generator was used to control a conventional
      13.56 MHz RFGD circuit to provide plasma on and off times throughout a wide range
      of duty cycles. Starting monomers included fluorocarbon monomers (C8F16O and
      C3F6O) and more conventional unsaturated monomers [acrylonitrile (C3H3N) and
      vinyl trimethyl silane (C5H12Si)]. With each of these monomers progressive, large
      scale changes in the molecular structure of the plasma deposited films were noted
      with systematic variations in the RF duty cycle. Film characterizations were
      performed using electron spectroscopy for chemical analysis (ESCA) and fourier
      transform infrared (FTIR) analysis. In the case of fluorocarbon (FC) films,
      systematically decreasing plasma on time at a constant off time resulted in
      enhanced CF2 and CF3 content compared with that seen with the less highly
      fluorinated groups. There was virtually no oxygen atom incorporation in the FC
      films obtained from the oxygen containing monomers. Overall, a dramatic decrease
      in cross-linking of the FC polymer films was observed with decreasing RF duty
      cycles. A highly ordered Teflon-like structure was obtained for the lowest duty
      cycles. In the silane experiments, a systematic variation in the ratio of Si-H/Si
      CH3 groups was observed, with this ratio increasing as the RF duty cycle
      decreased. Experiments with C3H3N revealed an increasing surface density of -CN
      groups with decreasing RF duty cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268549
TI  - Analysis of albumin deposits on hydroxylated siloxane films. Implications for
      surface treatment of medical devices.
AB  - The authors have developed methods to enhance albumin binding to modified
      silicone rubber (SR) films. An intermediate bifunctional coupling agent,
      polyvinylmethyl siloxane-comethyl-1-ethanol siloxane (PVMS-CO-MES), is prepared
      from a cyclic tetramer, vinyl-methyl siloxane, by an oxymercuration-demercuration
      reaction, and cross-linked to silicone rubber under mild peroxide catalytic
      conditions. Free mercury on the surface was obtained under many reaction
      conditions and is shown to materially enhance 125I-labeled albumin binding. The
      mechanism most likely occurs via disulfide bond breakage, protein denaturation,
      and aggregation. The possible role of iodine-mercury bonds, an artefactual
      source, is ruled out with the aid of total internal reflectance-fluorescence
      measurements of the albumin adsorption rate constant. Although in situ albumin
      aggregation via disulfide bond breakage is a potentially attractive method for
      biocompatible protein gel formation, the toxicity of mercury makes the current
      method unfit for clinical practice.

PMID- 8268550
TI  - Antithrombotic activity of a lumbrokinase immobilized polyurethane surface.
AB  - Six fractions of strong and novel fibrinolytic enzymes (lumbrokinase, LK) were
      extracted from the earthworm Lumbricus rubellus. The enzymes in these fractions
      appeared to be very stable and showed greater antithrombotic activity than other
      currently used antithrombotics. The authors immobilized an LK fraction that shows
      the most potent fibrinolytic activity on a polyurethane (PU) surface to
      investigate its enzymatic and antithrombotic activity. The methanol extracted PU
      surface was treated with a 3% (wt/vol) maleic anhydride methylvinyl ether
      copolymer (MAMEC) solution and finally incubated in an LK solution in PBS (pH
      7.4). The immobilized LK activity was estimated by the fibrin plate method and
      caseinolytic activity assay. The antithrombotic activity was evaluated by in
      vitro 125I-fibrinogen adsorption in fresh whole blood and 99mTc platelet adhesion
      tests. In addition, the occlusion time was determined through ex vivo rabbit A-A
      shunt experiments. The content and unit activity of immobilized LK were found to
      be 24 micrograms/cm2 and 18 IU/cm2, respectively. The relative activity ratio of
      immobilized LK to soluble LK was found to be approximately 34%. Immobilized LK
      was stable within a various pH range and resistant to inhibitors and thermal
      inactivation. Less fibrinogen was adsorbed and fewer platelets adhered on an LK
      immobilized surface than on PU and PU-MAMEC controls. The ex vivo occlusion time
      of untreated PU and PU-MAMEC surfaces were only 32 and 42 minutes, respectively.
      But that of LK-immobilized PU was extended to 140 minutes.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8268551
TI  - An N-substituted polyurea coating with high affinity for heparin.
AB  - A new N-substituted polyurea with tertiary amino groups in the polycarbamidic
      chain (NPUTA) has been synthesized. The polymer is soluble in C1-C4 alcohols, has
      high adhesion to polar molds, and has high H2O uptake (130-150%). The material
      can be coated on many biomaterials (polyurethanes, charcoal hemosorbents,
      cellulosic hemodialysis membranes), and high amounts of heparin can be adsorbed
      onto treated surfaces. NPUTA cast from 0.5-3.5% ethanol solutions can absorb
      large amounts of heparin from anti-coagulant solution (40-60 micrograms/cm2) and
      heparinized plasma. Heparin release into phosphate buffered saline (PBS) solution
      or plasma is minimal. The influence of NPUTA solution concentration and pre
      absorbed heparin on the protein adsorption, platelet adhesion, surface induced
      hemolysis, and complement activation of these films has been investigated.
      Radiolabeled protein assays, radiolabeled platelet assays, and other methods were
      used. It was shown that modified surfaces for the listed materials, with
      heparinization, demonstrate improved in vitro blood compatibility without any
      changes in functional properties. For example, treatment with NPUTA/heparin does
      not reduce sorption of middle molecules by activated charcoal hemosorbent, while
      markedly and significantly decreasing platelet adhesion and complement
      activation. NPUTA/heparin modified, glutaraldehyde treated bovine pericardium
      exhibited significantly reduced calcification in a rat subcutaneous implant
      model. Other ex vivo circulation experiments also confirm the blood compatibility
      of different NPUTA treated surfaces.

PMID- 8268552
TI  - A new amphiphilic block co-polymer with improved elastomeric properties for
      application in various medical devices.
AB  - The authors have demonstrated that an amphiphilic block co-polymer composed of 2
      hydroxyethyl methacrylate (HEMA) and styrene (HEMA-st) showed excellent blood
      compatibility in in vitro, ex vivo, and in vivo experiments. The poor elastomeric
      properties of HEMA-st, however, have been an obstacle to its wider application in
      medical devices. To improve the mechanical properties of HEMA-st, the authors
      have developed a new amphiphilic block co-polymer composed of HEMA and
      octylstyrene (HEMA-oct). The size and morphology of the microdomain structures of
      HEMA-oct observed by transmission electron microscopy were similar to those of
      HEMA-st. Kink resistance tests showed improved elastomeric properties of HEMA-oct
      over HEMA-st. The blood compatibility of HEMA-oct was evaluated using an in vitro
      flow cell system combined with an epifluorescent video microscope, in which real
      time platelet adhesion and activation in whole blood can be observed and
      quantified, and ex vivo rabbit A-A shunt experiments. HEMA-st and a polyurethane
      (Pellethane 2363-80AE) were used for comparison. In a flow cell system, both HEMA
      st and HEMA-oct showed minimal platelet coverage on the surfaces and less
      platelet activation as measured by beta-thromboglobulin (beta-TG), whereas
      Pellethane showed a considerable amount of platelet coverage with high beta-TG
      production. A-A shunt occlusion times were 309 +/- 31.2 min for HEMA-st, 251 +/-
      47.7 min for HEMA-oct, and 30 +/- 3.4 min for Pellethane.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8268553
TI  - Newly designed tissue adhesion prevention technology based on photocurable
      mucopolysaccharides. In vivo evaluation.
AB  - Tissue adhesion after surgery occasionally causes serious complications. The
      authors have been developing photocurable mucopolysaccharides for a tissue
      adhesion prevention material that meets requirements such as nonadherent surface
      characteristics, biocompatibility, biodegradability in accordance with the wound
      healing rate, and nontoxicity. Mucopolysaccharides (hyaluronic acid and
      chondroitin sulfate) partially derived with photoreactive groups, such as
      cinnamate or thymine, were subjected to ultraviolet (UV) irradiation to produce
      water insoluble gels via intermolecular photodimerization of photoreactive
      groups. Photocured films that covered injured liver surfaces of rats were
      implanted for as long as 4 weeks and histologically evaluated. In vivo
      performance, including tissue adhesion prevention, biodegradability, and
      mechanical flexibility of the films, was found to be controlled by the type of
      mucopolysaccharides, the type of photoreactive groups, and their degrees of
      substitution (DS). Photocured films with lower DS, which had high water
      swellability and flexibility, prevented tissue adhesion and exhibited enhanced
      biodegradability. As an increase in DS occurred, tissue adhesion prevention,
      biodegradability, and mechanical flexibility were reduced. Control of the
      biodegradation rate was feasible. Minimum inflammatory reaction was noticed.

PMID- 8268554
TI  - The fluid dynamic effect on protein adsorption in left ventricular assist
      devices.
AB  - Plasma protein adsorption onto an artificial surface is strongly influenced by
      not only the surface characteristics of materials, but also by the fluid dynamics
      inside the blood pump, and it would influence subsequent platelet adhesion or
      activation, which plays a major role in the initiation of thrombus formation at
      the blood-material interface in vivo. In vitro flow visualization of an
      electrohydraulic LVAD was performed by a video camera (CCD, Hitachi) and an image
      processor (PC VISION PLUS) with an IBM PC. The electrohydraulic LVADs were
      implanted in mongrel dogs of approximately 20 kg. The authors sectioned the blood
      contacted ventricle after animal death according to the level of shear rate.
      Because analysis of adsorbed protein might be influenced by the size of the
      ventricle segment, the number of segments was limited to eight per ventricle.
      Platelet adhesion and its morphology were observed by scanning electron
      microscopy (SEM). Adsorbed plasma proteins (fibrinogen, albumin, and IgG) on each
      segment were quantified by enzyme linked immunosorbent assay (ELISA). The
      specimens were soaked in 2% (wt/vol) SDS/PBS for 2 days and the released protein
      concentration assessed. A well developed large vortex was observed at the center
      of the artificial ventricle. Polyurethane blood pumps displayed different degrees
      of protein adsorption and subsequent platelet adhesion on each segment.

PMID- 8268555
TI  - Urea kinetic modeling with a prototype urea sensor in the spent dialysate stream.
AB  - The authors have previously demonstrated the feasibility and accuracy of urea
      kinetic modeling (UKM) based on monitoring urea concentration in the spent
      dialysate stream (SDS) throughout the hemodialysis (HD) session. They describe
      here a prototype urea sensor for this purpose and initial experience with HD
      patients. The sensor is based on ammonium ion and reference electrodes housed in
      a cell through which the entire SDS passes. The two electrode tips are bathed in
      urease solution on one side of a dialysis membrane; the SDS flows along the
      adjacent side. Urea diffusing across the membrane from the SDS is converted by
      the urease into ammonium ion, which is measured by the electrode pair. For
      evaluation, the prototype flowthrough urea sensor was installed in the SDS of a
      Cobe Centry 3 HD machine for 36 HD sessions. Independent measurement demonstrated
      a linear relationship between mv output of the sensor and logarithm of SDS urea
      concentration. The use of SDS urea concentration time profiles obtained with this
      sensor to obtain accurate values of patient protein catabolic rate (PCR) and KT/V
      is illustrated. Incorporation of urea sensors such as this prototype into HD
      machines, will permit complete automation of UKM in the near future.

PMID- 8268556
TI  - Development of a blood urea monitoring system for the closed loop control of
      dialysis.
AB  - Optimal hemodialysis prescription through real-time blood urea (BU) monitoring
      and closed loop control of urea removal would be of significant clinical value.
      Progress toward a bedside BU analyzer and a control system is described here. An
      Amicon Minifilter inserted into the arterial bloodline provides a 1 ml/min stream
      of protein free ultrafiltrate for analysis. In vitro tests with bovine blood have
      shown excellent correlation between plasma (CP) and ultrafiltrate (CU) urea
      levels: CP = 0.961CU + 0.071, (n = 34, r = 0.998). In clinical hemodialysis
      studies, CU accurately represented the decay in CP. The BU analyzer uses a
      standard UV endpoint assay with a proportioning roller pump. The absorbance of
      the reacted mixture is read in a spectrophotometer after a 5 min incubation. For
      future control system design, the transfer function (TF) of the BU analyzer was
      measured using multifrequency binary testing. The data indicated that the
      analyzer may be modeled by a second order TF with a pure time delay. The same
      form of TF was also found to describe the Minifilter. Control of the removal rate
      of NaCl (substituted for urea) through automatic dialysate flow adjustment has
      been achieved with a simulated dialyzer-patient circuit (using a conductivity
      probe in place of the BU analyzer). A modified BU analyzer using computer
      controlled precision syringes for improved sample processing time and accuracy is
      also reported.

PMID- 8268557
TI  - In vivo verification of an automatic noninvasive system for real time Kt
      evaluation.
AB  - It is generally accepted that morbidity and mortality of hemodialysis patients is
      related to dialysis quantitation. Currently available methods for the
      quantitation of dialysis require blood sampling or a continuous measurement of
      changes in urea concentration during treatment. These maneuvers are time
      consuming and expensive, and are generally performed, at most, once per month.
      The authors introduce an on-line, automated method for measurement of dialyzer
      electrolyte clearance comparable to urea clearance by using dialysate
      conductivity sensors placed pre and post dialyzer, and measuring conductivity at
      three different pre dialyzer levels. Conditions that reduce clearance, such as
      recirculation or fiber clotting, are automatically taken into account so that the
      method measures effective clearance rather than dialyzer clearance. In vitro and
      in vivo studies validate the method. Results are immediately available and can be
      used to address problems such as improper needle placement and access
      recirculation. In addition, repetitive electrolyte clearance data can serve to
      enhance quality assurance programs with respect to verifying the function of
      reused or new dialyzers. Appropriate algorithms can be used to calculate
      delivered Kt/V.

PMID- 8268558
TI  - A disposable urea sensor for continuous monitoring of hemodialysis efficiency.
AB  - A new sensor for the on-line measurement of urea in the dialysate output is
      described. The sensor is based on a differential measurement of conductivity
      changes induced by the urease-catalyzed hydrolysis of urea. The use of screen
      printing for the batch-fabrication of the basic transducers results in cheap
      disposable devices. In addition, the sensor has been designed to fit into a
      standard male luer-adapter, and can be plugged directly into the dialysate line.
      The in vitro response is linear to urea concentrations exceeding 6620mM. A
      resolution of 20020 microM has been achieved with a baseline stability of 50
      microM/hr. Interferences caused by fluctuations in the ionic strength and the
      consequent conductivity changes are effectively suppressed by the differential
      sensor pair. The efficiency of this suppression is expressed in a common mode
      rejection ratio of typically 40 to 50. Preliminary ex vivo results show the
      feasibility of the concept. The sensor principle is not restricted to urea but
      can be extended to other molecules of interest for hemodialysis monitoring, such
      as creatinine and L- and D-amino acids.

PMID- 8268559
TI  - Urea kinetic modeling in continuous peritoneal dialysis patients. Effect of body
      composition on the methods for estimating urea volume of distribution.
AB  - Body composition can have a significant effect on methods for estimating urea
      volume (V) and fractional clearance (KT/V) in patients with renal failure. These
      effects were examined in 27 men on continuous ambulatory peritoneal dialysis
      (CAPD). Urea volume was calculated as 0.6% of body weight (V.6), by the Watson
      formula (VW) and by the Hume formula (VH). Patients were classified as obese (>
      120% of ideal body weight), normal (90%-120% of ideal weight), or wasted (< 90%
      of ideal weight). A patient was considered adequately dialyzed if his weekly KT/V
      urea exceeded 1.70. Only 75% of subjects were classified as adequately or
      inadequately dialyzed by all three methods. Six subjects had KT/V0.6 < 1.70 and
      KT/VW > 1.70; five subjects had KT/VH < 1.70 and KT/VW > 1.70; and two subjects
      had KT/V0.6 < 1.70 and KT/VH > 1.70. In the obese group, KT/V0.6 (1.62 +/- 0.67)
      was significantly less than KT/VW (1.93 +/- 0.76; p < 0.001) and KT/VH (1.92 +/-
      0.78; p < 0.001). Fractional errors in V and KT/V between any two methods were
      highly correlated with percent deviation from ideal body weight (r = 0.81 or
      higher). In peritoneal dialysis patients, excessive body weight affects the
      estimates of V and KT/V urea by certain methods, and may lead to erroneous
      impressions about the adequacy of CAPD.

PMID- 8268560
TI  - A higher blood flow window of reduced thrombogenicity and acceptable
      fragmentation in a hollow fiber hemodialyzer.
AB  - The effect of pulsatile blood flow on platelet thrombogenicity and platelet
      fragmentation (PF) in a hollow fiber hemodialyzer (HFD) was quantified with 111In
      labeled platelets and 125I labeled fibrinogen; 150 ml of blood was collected from
      Beagle dogs, Yorkshire pigs, and a human volunteer (non-smoker). Platelets were
      labeled with 111In tropolone (300 microCi) and fibrinogen was labeled with 125I.
      Sham dialysis (SHD) was performed with 120 HFDs (0.9 meter2) at 37 degrees C,
      with flow-rates of 150, 250, 500, and 950 ml/min.; after SHD, the washed HD
      radioactivity was measured with an ionization chamber. PF was measured by flow
      cytometry with GP IIb-IIIa murine monoclonal antibody. Platelet deposition
      decreased significantly for 3 species at higher flow; fibrinogen deposition (10
      12%, 55-65 mg/m2), was not affected by flow. Adherent platelet thrombus decreased
      from (8.2 +/- 3.4) to (3.1 +/- 1.0) with human blood as flow rate increased from
      150 to 950 ml/min; platelet thrombus level also decreased significantly (p <
      0.005) from (20.3 +/- 6.2) to (4.5 +/- 1.9) with canine blood. Higher values were
      obtained for canine than human and porcine platelets. Platelet fragmentation, on
      the other hand, increased from 2.1-2.2% to 10.2-11.3% with increase of flow. Like
      platelets, deposition of canine fibrinogen was slightly higher than that of pig
      and human. The studies of adherent thrombus and platelet fragmentation identified
      an important flow-window of reduced thrombogenicity and acceptable fragmentation,
      encouraging extracorporeal circulation at higher blood flow.

PMID- 8268561
TI  - The adjustment of post dialytic dry weight based on non-invasive measurement of
      extracellular fluid and blood volumes.
AB  - One of the major problems in the clinical practice of hemodialysis is an
      incorrect estimation of post dialytic (PD) dry weight. Underestimation of dry
      weight leads to hypovolemia induced hypotension, and overestimation to
      hypertension, pulmonary edema, and left ventricular hypertrophy. Because of the
      insensitivity of clinical variables to estimate dry weight, a more accurate
      technique is warranted. For this purpose and for the continuous surveillance of
      changes in blood volume (BV) during hemodialysis, two non-invasive techniques
      were applied. Based on post dialytically obtained extracellular fluid volume
      (EFV) values, measured by means of a conductivity method, 30 stable hemodialysis
      patients were divided into three groups for further analysis: de- (n = 9), normo-
      (n = 15), and overhydrated (n = 6). Using an on-line optical reflection method,
      changes in BV were measured continuously during therapy. Mean BV decrease,
      corrected for UF, differed slightly between the three groups (0 = 1.84 +/- 2.06,
      N = 3.20 +/- 1.80, D = 4.20 +/- 1.60 %/L). However, eight hypotensive episodes
      occurred in group D versus none in groups N and O. These hypotensive episodes
      were characterized by a greater reduction of BV--corrected for ultrafiltration-
      from the start of treatment until the moment of hypotension (6.96 +/- 2.21 %/L),
      compared with the 22 non hypotensive controls (2.16 +/- 2.01 %/L, p < 0.001).
      Based on the PD EFV dry weight of the overhydrated and dehydrated patients was
      decreased and increased, respectively, by 500 g after each session, until PD EFV
      was within normal bounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268562
TI  - In vivo long-term evaluation of the Utah electrohydraulic total artificial heart.
AB  - An electrohydraulic total artificial heart (EHTAH) has been developed and
      evaluated by long-term in vivo studies. The EHTAH is composed of blood pumps with
      an interatrial shunt (IAS), an energy converter, and electronics. The EHTAH with
      external electronics was implanted in four calves weighing from 81-90 kg. Two
      animals died on the 1st and 5th post operative days, the third animal survived
      for 32 days, and the fourth for 159 days. The IAS was free of thrombus at autopsy
      in all animals. The longest surviving animal increased in size from a pre
      operative weight of 81 kg to 134 kg on day 144. Cardiac output ranged from 9.3 to
      10.5 L/min, whereas right and left atrial pressures increased with the calf's
      growth from 4-10 to 16-20 mmHg and from 8-14 to 18-22 mmHg, respectively. The
      animal favorably tolerated up to 3.4 km/hr of treadmill exercise, both
      hemodynamically and metabolically. The elevation of atrial pressures during
      treadmill exercise was significantly alleviated by employing an automatic control
      mode. It is concluded that the device has the potential to be a totally
      implantable system for permanent use.

PMID- 8268563
TI  - Adaptive responses of total artificial heart animals to treadmill exercise.
AB  - The hemodynamic and metabolic adaptations to exercise in five calves implanted
      with the Utah-100 total artificial heart (TAH) were investigated. The outputs of
      the left and right ventricles (LCO, RCO) were measured with a cardiac output
      monitoring and diagnostic unit (COMDU). Arterial and venous oxygen content (CaO2,
      CvO2) and blood lactate levels (Lac) were measured by blood gas analysis and
      enzymatic methods. Oxygen consumption (VO2), oxygen delivery (DO2), oxygen
      extraction rate (EO2), index of metabolic adequacy (IMA), and systemic and
      pulmonary vascular resistance (SVR, PVR) were calculated. The intensity of
      exercise was categorized into three horizontal grades: low speed (LS) 0.7-1.0
      mph, medium speed (MS) 1.0-1.4 mph, and high speed (HS) 1.4-1.8 mph, each for 30
      min. During LS, MS, and HS exercise, the LCO, RCO, LAP, RAP, VO2, DO2, and EO2
      all increased, and the SVR and PVR decreased. During exercise, there was a
      positive correlation between DO2, EO2, and VO2. The blood pH, BE, SBE, and
      lactate levels were within normal ranges, and the IMA exceeded 1.5, denoting that
      tissue perfusion was adequate and anaerobic metabolism did not occur. This study
      implies that Utah-100 TAH animals could physiologically accommodate to exercise
      with an intensity of up to 1.8 mph for 30 min by increasing cardiac preload,
      cardiac output, oxygen delivery, and oxygen extraction rate, and by decreasing
      systemic and pulmonary vascular resistance without transition to anaerobic
      metabolism.

PMID- 8268564
TI  - A compact and noise free electrohydraulic total artificial heart.
AB  - The ABIOMED total artificial heart (TAH) is designed for long-term tether-free
      use in patients with end-stage heart disease. Blood pumping is achieved through
      hydraulic fluid motion across flexing diaphragms. The hydraulic power is derived
      from a miniature centrifugal pump (50% efficiency). Flow directional change
      needed for alternate left and right filling and ejection is achieved with a
      rotary valve. With no mechanical contact with the flexing membrane, the wedge
      angle between the two pumps sandwiching the energy convertor can be easily
      optimized for anatomic fit. The blood pumps (80 ml strokes) are fitted with
      trileaflet polyetherurethane valves (24 mm). The TAH is implanted using twist
      lock stepless quick connectors to the inflow cuffs and outflow grafts. Left-right
      flow balance is achieved with an atrial hydraulic shunt placed between the left
      cuff and inflow valve. Animal studies show that the TAH fits very well in Long
      Horn calves weighing 90 to 100 kg and can provide cardiac output in excess of 10
      L/min. A cadaver (85 kg) study showed the TAH fits within the pericardial region.

PMID- 8268565
TI  - A non-invasive technique to quantify in vitro bioprosthetic valvular coaptation.
AB  - The functional relationship between valvular leaflet stress and coaptive geometry
      may provide insight into a bioprosthetic heart valve's ability to maintain
      coaptation under a broad range of physiologic operating conditions. Previous
      investigators have only indirectly measured coaptation geometry. A non-invasive
      in vitro technique is demonstrated to directly quantify the coaptive geometry of
      bioprosthetic heart valves. A discussion is provided detailing the use of this
      information in a finite element model to determine the functional relationship
      between valvular leaflet stress and coaptation geometry. Video images of the
      stent post deflections and coaptive geometry for size 21 mm, 23 mm, and 25 mm
      Hancock Aortic Pericardial heart valves are obtained based on back light
      illumination of each valve's coaptive area at discrete back pressures. The
      resulting images are analyzed using image processing and motion analysis
      techniques. Results indicate that at back pressures greater than 50-75 mmHg the
      coaptive area remains constant. There is a decrease in coaptive depth at the
      valve's periphery, whereas the point of maximum coaptation maintains position
      approximately midway along the free margin. Good agreement is found between the
      experimentally determined and finite element model's predicted coaptation
      geometry.

PMID- 8268566
TI  - Closing behavior of a new bileaflet mechanical heart valve.
AB  - Recently, the in vivo cavitation potential has become a primary concern among
      manufacturers of new mechanical heart valves (MHV). An experimental/computational
      program was designed to investigate each of the flow parameters involved. It was
      established that the closing velocity of the leaflet holds the key to MHV
      cavitation. One of the novel concepts of the new bileaflet mechanical heart valve
      (1205-MHV) was its ability to operate with a relatively small angular excursion
      that led to a much smaller closure velocity at impact (as compared with control
      valves). This is believed to significantly reduce the cavitation potential. The
      1205-MHV is characterized by a longer valve body, with the hinges protruding
      further upstream. The unique design allows the valve the freedom to open as much
      as 90 degrees. The closure velocities are reduced by a smaller leaflet excursion
      (50 degrees), combined with a floating hinge that allows absorption of part of
      the impact energy at closure. The impact velocities of the 1205-MHV leaflets at
      closure were measured by a laser sweeping technique that monitored the leaflet
      closing motion with a precision of 5 microseconds within the last 3 degrees
      before impact. The 27 mm 1205-MHV (the largest size) was tested in the program by
      mounting the valve in the mitral position of a physiologic mock circulatory loop.
      The valve was tested at 70, 90, and 120 bpm. The results were compared with those
      of a St. Jude Medical 29 mm MHV. The closure velocities measured with the 1205
      MHV were significantly lower than those measured with the control valve.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8268567
TI  - Morphology and integrity of endothelial cell monolayers inside a ventricle shaped
      perfusion chamber.
AB  - The long-term maintenance of patients with failing hearts on cardiac prostheses
      requires prevention of device related thromboembolic events. This challenge is
      being addressed by endothelialization of the blood sacs. However, the practice of
      establishing and maintaining a durable endothelial cell monolayer inside a
      beating prosthesis has not been fully realized. Thus, before exposing endothelial
      cell monolayers to the hemodynamics inside an artificial heart, the authors
      studied the effect of various flow patterns in a ventricle shaped chamber on the
      integrity and morphology of the endothelium. After 20 hours of superfusion by
      pulsatile flow, there were no denudation signs in the jet, where shear stress was
      1.5 dynes/cm2. However, there was measurable damage to the monolayer close to the
      periphery of the eddies (turbulent flow) at 0.15 dynes/cm2. In either case, there
      were no signs of cell alignment with the flow, but there were changes in cell
      morphology compared with that of static control. These findings suggest that
      adjustment of endothelial cells in response to frictional forces occurs even at
      low shear stresses and that random velocity fluctuations might jeopardize the
      integrity of endothelial cell monolayers.

PMID- 8268568
TI  - Effects of a total artificial heart right stroke volume limiter on left-right
      hemodynamic balance.
AB  - In a completely implantable total artificial heart (TAH), the left-right flow
      difference attributable to higher volumetric efficiency of the right pump and
      bronchial artery shunting has always been a significant problem. The automatic
      control of the Cleveland Clinic-Nimbus TAH accommodates for the left-right flow
      difference when the beat rate is below maximum (AUTO range). However, at its
      maximum beat rate (MAX), high left atrial pressure (LAP) (greater than 25 mmHg)
      with relatively low right atrial pressure (RAP) (less than 8 mmHg) were observed
      both in vitro and in vivo, suggesting the need for a stroke volume limiter (SVL)
      of the right pump. In vitro volume loading tests showed 10%, 15%, and 20% SVLs
      prevented a disproportionate increase of LAP. In vivo studies in five Holstein
      calves also showed a balanced LAP-RAP relationship with 10% and 15% SVLs at MAX.
      The left pump flow was not affected by this range of SVLs either in vitro or in
      vivo. Pulmonary function was maintained with either size SVL, with autopsies
      revealing absence of pulmonary congestion and minimal pleural effusions in two
      calves surviving for more than 1 month. Although additional studies are needed to
      determine the appropriate size of the SVL, both 10% and 15% SVLs were effective
      in maintaining left-right hemodynamic balance in this TAH.

PMID- 8268569
TI  - An annular compliance chamber for the Pennsylvania State University electric
      total artificial heart.
AB  - To eliminate the need for a separate parapleural compliance chamber, we are
      currently investigating the feasibility of an annular compliance chamber. This
      chamber wraps around the energy converter and fits between the blood pumps of the
      Pennsylvania State University electric total artificial heart. For the 100 cc
      total artificial heart, the compliance chamber volume is 76 ml and the tissue
      contacting surface area is approximately 85 cm2. The chamber is made of Dacron
      velour covered segmented polyether polyurethane urea. The annular compliance
      chamber was evaluated in vitro by comparing pump balance control performance
      against that obtained with an open vent. In the CVP range of 5-12 mmHg, LAP was
      maintained within 1 mmHg of the values obtained with a vent. Studies continue to
      determine the range of volumes over which the chamber is effective, differences
      in rates of diffusion, and performance during changes in barometric pressure.

PMID- 8268570
TI  - Hemodynamic changes with posture in calves with total artificial heart.
AB  - Hemodynamic changes with posture, sitting versus standing, were analyzed in five
      Holstein calves with the Cleveland Clinic-Nimbus TAH. This total artificial heart
      (TAH) has a left master alternate control mode that adjusts the pump rate and
      consequently pump flow proportional to the pulmonary venous return to the left
      pump (AUTO period). However, in this series of experiments, the pump reached its
      maximum beat rate within 1-5 days post operatively, after which pump flow could
      not increase (MAX period). Hemodynamic parameters (RAP, LAP, PAP, AoP, and pump
      flow) were obtained every 15-20 min throughout the experiments for as long as 120
      days and averaged for each posture for each period. During the AUTO period, the
      flow while standing was significantly higher than that while sitting (standing:
      8.7 +/- 0.2 L/min; sitting: 7.5 +/- 0.4 L/min; p < 0.05), and the systemic
      vascular resistance (SVR) was significantly lower (standing: 895 +/- 93
      dyne.sec.m-5; sitting: 1,041 +/- 124 dyne.sec.m-5; p < 0.05). During the MAX
      period, the AoP and SVR standing were significantly lower than those sitting (AoP
      standing: 91 +/- 7 mmHg; AoP sitting: 98 +/- 7 mmHg; p < 0.05; SVR standing: 652
      +/- 75 mmHg; SVR sitting: 730 +/- 96 mmHg; p < 0.05). The Cleveland Clinic-Nimbus
      TAH responded well to these changes in position, increasing pump flow and
      maintaining the AoP during the AUTO period.

PMID- 8268571
TI  - Evaluation of nickel-cadmium battery packs for mechanical circulatory support
      devices.
AB  - The mismatching of battery cell capacities within a rechargeable battery pack can
      result in reduced cycle life and operating time, as well as an increased safety
      risk due to gas release, which is a concern when used in implantable medical
      devices, such as a ventricular assist device (VAD). Two groups of four
      nickel/cadmium (Ni/Cd) battery packs containing 10 cells each (i.e., 12 volt
      packs) were evaluated for their cycle life, safe operating time, and the impact
      of mismatched cell capacities within the pack. Four control battery packs
      containing capacity matched cells (within +/- 0.4% of mean) and four battery
      packs each containing one low capacity cell (4.7-10.7% below mean) together with
      nine high capacity matched cells (within +/- 0.6% of mean) were charge/discharge
      cycled at 37 degrees C using a 9.7 W average pulsatile discharge load and a 30
      minute discharge time on each cycle. Periodically, the battery packs were fully
      discharged down to 10 volts and each cell was monitored for negative voltages.
      The capacity matched and mismatched packs yielded similar performance curves,
      with an initial decline in mean total operating time until a plateau was reached
      of 41.1 +/- 1.5 and 41.8 +/- 1.8 minutes of discharge time, respectively. The
      mean total operating times of the matched and mismatched packs began to decline
      again after approximately 670 and 635 cycles, respectively. Cell voltage
      monitoring showed no negative voltages, indicating that no gases were released
      from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268572
TI  - A completely implanted left ventricular assist device. Chronic in vivo testing.
AB  - A completely implantable left ventricular assist device (LVAD) designed for
      permanent circulatory support has recently been tested in animals without the use
      of percutaneous leads, using transcutaneous energy transmission and wireless
      telemetry. The LVAD consists of a brushless DC motor and rollerscrew energy
      converter, a pusher plate actuated blood pump with a seamless segmented
      polyurethane blood sac, Bjork-Shiley Delrin disk monostrut valves, an implanted
      compliance chamber, an implanted electronic controller and battery, and a
      transcutaneous energy transmission system. The blood pump/energy converter
      assembly weighs 565 g and displaces 295 cc. The dynamic stroke volume is 60 ml,
      and the maximum output is 9 L/min. Pump output is automatically controlled to
      maintain full stroke volume as preload varies. Hall effect sensors for detecting
      rotary position of the motor are the only sensors used. Six bovine implants were
      performed, with durations of 84, 208, 244, 130, 70 (ongoing), and 15 (ongoing)
      days. Four animals used two-way telemetry, whereas the remaining two used one-way
      (outgoing) telemetry. These first chronic in vivo tests with the Penn State
      completely implanted LVAD system have demonstrated that it is a feasible solution
      to long-term ventricular support.

PMID- 8268573
TI  - Flow visualization evaluation of secondary flow in a centrifugal blood pump.
AB  - To design a less hemolytic and more antithrombogenic centrifugal blood pump,
      secondary flow, i.e., vortex and turbulent flow, must be properly controlled. An
      irregular stream pattern is a cause of hemolysis, and good wash-out around the
      shaft minimizes thrombus formation. In this study, flow visualization methods
      were applied to evaluate secondary flow in a centrifugal blood pump. Correlation
      with results of in vitro hemolysis tests was investigated. Separation of the
      stream lines from the vanes and patterns implying the existence of vortices were
      observed in the impeller that showed high hemolysis. By adjustment of vane
      angles, these irregular patterns could be minimized, and hemolysis decreased as
      well. Using a similar technique, the flow pattern at the back of the impeller
      could be visualized, which enabled further investigation of the effects of
      secondary flow on thrombus formation. This flow visualization was effective in
      examining secondary flow patterns.

PMID- 8268574
TI  - Effects of pulsatile reperfusion on globally ischemic myocardium.
AB  - To evaluate the effects of pulsatile reperfusion on the post ischemic myocardium,
      two categories of sheep were put on cardiopulmonary bypass (CPB). In Category I,
      the hearts of 23 sheep were arrested by global ischemia for 30 min, reperfused
      with pulsatile flow in 10 animals (P group), and non pulsatile flow in 13 animals
      (NP group), and then defibrillated. The incidence of ventricular fibrillation was
      much higher in the NP group than the P group, 77% versus 40% (p < 0.05). The
      lipoperoxide products and creatinine kinase from coronary sinus blood were
      elevated, but there were no significant differences between the two groups during
      2 hour reperfusion. In the P group, less ultrastructural damage was observed, and
      Na+ and H2O accumulations in the subendomyocardium were significantly less than
      in the NP group, at 7.11 +/- 0.60 versus 9.98 +/- 1.10 mg/g dry weight (p < 0.05)
      and 82.58 +/- 0.47% versus 84.3 +/- 0.38% (p < 0.05), respectively. In Category
      II, the ischemic time of 17 sheep (eight in the P group, nine in the NP group)
      was prolonged to 45 min, and animals were supported by CPB after defibrillation.
      Myocardial energy phosphates were measured with high-performance liquid
      chromatography, and triphenyltetrazolium chloride was used to delineate the
      infarct size. After 2 hour of reperfusion, there were no significant differences
      in myocardial AMP and ADP between the two groups.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268575
TI  - Extracorporeal membrane oxygenation for adult post cardiotomy cardiogenic shock
      using a heparin bonded system.
AB  - Extracorporeal membrane oxygenation (ECMO) for adult post cardiotomy cardiogenic
      shock has had limited success. The efficacy of a heparin bonded ECMO system was
      tested in 11 patients (eight men, three women; mean age: 63 +/- 8 years), all of
      whom were in post cardiotomy shock refractory to inotropes and intra-aortic
      balloon pumping (IABP). The system consisted of a right atrial-to-aortic loop
      using a hollow fiber oxygenator driven by a vortex pump. All blood contact
      surfaces were heparin bonded. Mean duration of support was 47.9 hr (range: 22
      92.5 hr). Mean prothrombin time, activated partial thromboplastin time, and
      activated clotting time during full support were 17 +/- 8, 57.5 +/- 38, and 152
      +/- 59 sec, respectively. Mean transfusion requirements for packed red blood
      cells, fresh frozen plasma, and platelets were 24 +/- 9, 19 +/- 9, and 38 +/- 15
      units, respectively. Complications included acute renal failure (1 patient),
      sepsis (3 patients), elevation of hepatic enzymes (7 patients), and myocardial
      infarction (11 patients). Oxygenator failure occurred in 4 patients, and 10
      patients had plasma hemoglobin levels exceeding 30 mg/L. No patient experienced
      focal neurologic deficit. Eight (73%) patients were weaned from ECMO. Five
      (45.4%) of these are alive and have been discharged home with a mean follow-up of
      317 +/- 76 days (range: 179-416 days). This heparin-free ECMO system allows rapid
      and simple deployment and provides effective short-term cardiopulmonary support.

PMID- 8268576
TI  - Emergency lung transplantation after extracorporeal membrane oxygenation.
AB  - In some patients with acute respiratory failure, the native lungs do not recover
      during extracorporeal membrane oxygenation (ECMO), or complications occur that
      preclude the meaningful continuation of ECMO therapy. In such cases, emergency
      lung transplantation (LTx) represents the only therapeutic alternative. Between
      May 1988 and April 1993, the authors have performed LTx after ECMO support in
      five of 111 lung or heart-lung transplantations (4.5%). Two patients presented
      with early graft failure after unilateral LTx. In these patients, ECMO was used
      as a bridging device to unilateral re-LTx for 1, resp. 11 days. One patient died
      6 months post-operatively from chronic rejection; the other underwent a third LTx
      and is doing well after 42 months. In three further patients already treated with
      ECMO for 5 to 12 days for ARDS (n = 2) or acute respiratory failure after liver
      and kidney transplantation, the native lungs did not recover (n = 2) or pulmonary
      hemorrhage developed. The last patient (unilateral LTx) and one of the former
      (bilateral LTx for ARDS) are long-term survivors (12, 30 months). The remaining
      patient (unilateral LTx for ARDS) had severe multiorgan failure at the time of
      his operation and died intraoperatively. The authors conclude that ECMO no longer
      represents a contraindication to subsequent LTx. Their results also support the
      continued investigation of this combined therapeutic approach.

PMID- 8268577
TI  - Extracorporeal membrane oxygenation after lung or heart-lung transplantation.
AB  - Extracorporeal membrane oxygenation (ECMO) has proven to be life-saving in cases
      of reversible lung injury. One potential application of ECMO in the field of lung
      transplantation is the support of the patient with acute pulmonary failure
      immediately after transplantation until the transplanted lung has resumed
      satisfactory gas transfer function. The authors have had experience with ECMO in
      three patients who have had acute pulmonary failure and inadequate oxygenation
      after bilateral single lung (BSLT) or heart-lung transplantation (HLT). Patient 1
      is a 47-year-old woman with alpha-1 antitrypsin deficiency who underwent a HLT
      and experienced fulminant pulmonary edema secondary to an intraoperative
      coagulopathy that required massive transfusion. Patient 2 was a 45-year-old man
      with a patent ductus arteriosus (PDA) that resulted in Eisenmenger's complex.
      Patient 2 underwent an HLT and experienced acute pulmonary failure. Patient 3 is
      a 58-year-old woman with an atrial septal defect (ASD) and pulmonary hypertension
      who underwent repair of the ASD and BSLT. Patient 3 experienced complete
      atelectatic collapse of the right lung and pulmonary edema of the left lung.
      These three patients had PO2 measurements of 23, 39, and 23 mmHg, respectively,
      despite receiving 100% FiO2 and maximal ventilatory support. All three patients
      were subsequently placed on ECMO and had improvement of their oxygenation.
      Patients 1 and 3 were successfully weaned from ECMO and extubated on post
      operative day (POD) 21 and 16, respectively. Patient 2 had significant
      improvement in oxygenation but died on POD 4 of persistent mediastinal
      hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268578
TI  - Development of an outside flow membrane oxygenator using a silicone hollow fiber.
AB  - A new membrane oxygenator was devised and assessed for performance in animal
      experiments. A silicone fiber membrane oxygenator, heat exchanger, and arterial
      blood reservoir are the components. The oxygenator is an outside flow type with
      minimum intrapulmonary resistance and, consequently, gas transfer is by gravity
      venous drainage. This device was used to conduct normothermic cardiopulmonary
      bypass (CPB) in 10 sheep over a period of 8 hrs (high flow group: 6 sheep, mean
      flow, 4.7 + 0.5 L/min; low flow group: 4 sheep, mean flow, 1 L/min). Performance
      was evaluated with gas transfer capacity, hematologic examination during CPB, and
      scanning electromicroscopic (SEM) appearance of the membrane after CPB. Blood gas
      was maintained with high PO2 and acceptable PCO2 levels throughout CPB. Plasma
      free hemoglobin was significantly low and fibrinogen was also maintained within
      physiologic levels. Scanning electron microscopy showed no thrombus formation on
      the membranes of either group. These results indicate this oxygenator to be quite
      adequate for gas exchange and prevention of blood cell trauma; it is also
      applicable to pulsatile or separating CPB because of the arterial blood
      reservoir.

PMID- 8268579
TI  - Current progress in the development of an intravenous membrane oxygenator.
AB  - In vitro testing of an intravenous membrane oxygenator (IMO) consisting of hollow
      fiber membranes arranged around a centrally positioned balloon is reported. A
      total of six IMO prototypes were mounted in a specially designed mock circulatory
      loop and perfused with physiologic saline or fresh abattoir ox blood to
      investigate their oxygen and carbon dioxide transfer capabilities. One IMO
      prototype was mounted in the flow loop and perfused with saline for 13 continuous
      days to test the durability and reliability of the prototype design. It is the
      authors' hypothesis that the rhythmic inflation and deflation of the balloon
      increases convective mixing and cross-flow of blood around the fibers, thereby
      enhancing gas exchange capabilities. The results of these trials support this
      contention, namely that gas exchange efficiency rose with increasing frequency of
      balloon pulsation. No significant deterioration in oxygen transfer was observed
      in the durability test prototype, which was continuously perfused with saline for
      13 days.

PMID- 8268580
TI  - A pumping intravascular artificial lung with active mixing.
AB  - Intravascular, as well as extracorporeal, artificial lungs need to be effective
      and efficient in transferring both oxygen and carbon dioxide. This paper
      describes the preliminary development of a device that not only is efficient in
      gas transfer, but also can reduce any pressure loss by providing its own pumping
      action. The exchange surfaces of the device consist of many short, microporous,
      hollow fibers arranged in layers like the threads of a screw and placed in a
      cross-flow configuration. Rotation of the device greatly increases gas transfer
      efficiency, by increasing the relative velocity between the blood and the fiber
      surfaces, and pushes the blood along a path similar to that of an Archime-dean
      screw. In vitro water tests of prototype devices indicate that the rotation can
      enhance the gas transfer rates by as much as a factor of six. In vitro blood
      studies indicate moderate blood pumping against zero pressure head, a simulation
      of veno-venous bypass.

PMID- 8268581
TI  - Large volume instillation of surfactant during extracorporeal life support
      improves lung function in lung lavaged rabbits.
AB  - The sometimes limited effect of surfactant therapy in neonates might be explained
      in part by an non homogeneous distribution of the surfactant after endotracheal
      instillation. This distribution can be improved significantly by increasing the
      fluid volume. The aim of this study was to evaluate the effect of two methods for
      gas exchange during a large volume instillation of surfactant on the outcome of
      this treatment in lung lavaged rabbits. In the control group (n = 6) gas exchange
      was maintained with continuous positive pressure ventilation (CV), whereas in the
      other group gas exchange was established with extracorporeal life support (ECLS)
      (n = 6) and intermittent sighs. Five hours after surfactant administration, an
      identical weaning procedure was started in both groups. The authors found
      significantly higher PaO2 values in the ECLS group than in the control group in
      the normocarbia state. All animals in the ECLS group could be weaned to room air
      maintaining normal blood gases, whereas all the animals in the control group died
      in the course of weaning. The ventilator efficiency index was significantly
      higher during the weaning period in the ECLS group, indicating better lung
      function, than in the control group. The authors conclude that a large volume
      instillation of surfactant is feasible by applying ECLS and intermittent sighs.
      Additional studies are needed to elucidate if this combined treatment will be an
      improvement over current surfactant therapy.

PMID- 8268582
TI  - A new tracheal prosthesis made from collagen grafted mesh.
AB  - The authors studied the efficacy of a new tracheal prosthesis made from mesh. The
      prosthesis, 50 mm long and 18-22 mm in diameter, is made from a Marlex mesh
      cylinder reinforced with a continuous polypropylene spiral that is grafted and
      coated with porcine collagen to increase its biocompatibility and provide an
      airtight seal during the initial implantation stage. Circumferential surgical
      resection and replacement of a seven to nine ring segment of the cervical trachea
      was performed in 20 adult mongrel dogs. At the time of surgery, a silicone tube
      was inserted into the tracheal prosthetic lumen to promote secretory
      transportation until the prosthesis was covered with host tissue. The silicone
      tube was removed during fiber bronchoscopy 1 month after surgery. With the
      exception of the prostheses in 3 dogs that died of unrelated causes, all were
      infiltrated by connective tissue and incorporated completely by the host. One of
      these 17 dogs died of suffocation caused by luminal stenosis 2.5 months after
      surgery, but the others survived until they were killed at more than 6 months.
      The luminal surfaces of the reconstructed tracheae were covered with respiratory
      epithelium to varying degrees, and in one dog killed at 22 months after surgery,
      confluent epithelization throughout the length of the prosthesis was confirmed
      histologically. In eight dogs, prosthetic luminal stenosis occurred because of
      overgrowth of granulation tissue, which generally was mild in all but three dogs.
      The authors conclude that this tracheal prosthesis is highly biocompatible and
      shows promise for clinical application.

PMID- 8268583
TI  - A new finger joint prosthesis.
AB  - A new finger joint prosthesis is being developed for the proximal and distal
      interphalangeal positions. Currently available "joint spacer" prostheses provide
      relief from pain and cosmetic improvement, but relatively poor long-term
      function. The new prosthesis employs a mechanical hinge at the joint. It is
      fabricated from titanium alloy (6A14V). The hinge mechanism avoids direct metal
      to metal contact by using high density polyethylene bearings. In vitro tests of
      the hinge mechanism have passed 75 million cycles of continuous flexure without
      failure (n = 12). The hinge also incorporates a mechanical limit stop to prevent
      hyperextension. The hinge mechanism is enclosed in a sealed elastomeric jacket
      that isolates the hinge from connective tissue ingrowth. The jacket, equivalent
      to an artificial synovial membrane, has an integrally textured exterior surface
      designed to promote tissue attachment to the implant to stabilize tissue capsule
      formation around the joint. To test the in vivo efficacy of the new design, a
      series of 12 devices were implanted in the knee joint position of adult rabbits.
      A jacketed prosthesis was implanted on one side, whereas 2 weeks later an
      unjacketed control was implanted contralaterally. The animals then were
      maintained for an 8 week period. At sacrifice, the implants were removed, and the
      response of the surrounding tissues was studied histologically. At the time of
      implantation, the range of motion of the joints was approximately 100-105
      degrees. There was a progressive loss in range of motion observed in both groups.
      The fibrous tissue capsule around the jacketed implants, however, was
      significantly reduced in thickness compared with the controls (mean thickness,
      1.5 mm vs. 4.5 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268584
TI  - How to convert the rabbit gracilis muscle into a neoanal sphincter.
AB  - For reconstruction of anal function in fecally incontinent patients,
      transposition of the gracilis muscle around the anal canal, with electrical
      stimulation to maintain contraction, seems practical. But the fast-twitch
      gracilis muscle is incapable of prolonged contraction without fatigue.
      Furthermore, the muscle must keep some tension between each stimulus. When the
      pressure decreases even transiently between stimuli, the neoanus cannot maintain
      continence. To fulfill these criteria, the neoanal sphincter must be stimulated
      at a frequency that can induce sufficient summation. We demonstrated that
      conditioning with long-term electrical stimulation will induce such summation at
      low frequency. The nerve to the gracilis muscle of rabbits was continuously
      stimulated at 5 Hz and 10 Hz for 4 to 8 weeks. This conditioning reduced the
      frequency necessary for summation, and conditioning at 10 Hz for 6 or 8 weeks
      induced sufficient summation (fusion index [FI] > 90%) at 20 Hz. The muscles
      conditioned at 10 Hz for 8 weeks showed sufficient summation (FI = 81%) at 15 Hz,
      a frequency that produced muscle contraction without fatigue, since even
      unconditioned muscle will remain contracted at 10 Hz without fatigue for 8 weeks.
      It is concluded that conditioning at 10 Hz for longer than 6 weeks produces
      enough summation at a low frequency stimulation to permit prolonged contraction.

PMID- 8268585
TI  - Localization of atherosclerosis in arterial junctions. Modeling the release rate
      of low density lipoprotein and its breakdown products accumulated in blood vessel
      walls.
AB  - Arterial bifurcations and surgically created junctions at anastomoses are places
      where blood flow may be disturbed and slow recirculation may occur. To address
      the hypothesis that such disturbances in flow may result in atherogenesis, the
      transfer of atherogenic substances from vessel wall to flowing blood was studied
      theoretically using a two dimensional T-junction model. Calculations showed that
      the transfer of atherogenic substances from vessel wall into flowing blood was
      suppressed in the two regions of disturbed flow, one in the main vessel, the
      other in the subsidiary vessel. The lowest release rates were at the points of
      flow separation and were found to be much lower than those in the undisturbed
      flow regions. Therefore, our mathematical model predicts that locally disturbed
      blood flows at arterial bifurcations and surgically created junctions are
      responsible for two distinct phenomena. First, they provide favorable conditions
      for the accumulation of LDL at the luminal surface, thus increasing the potential
      for lipid infiltration into the vessel wall, and second, they impair the transfer
      into blood of atherogenic substances accumulated in the vessel wall. Such mass
      transfer abnormalities may account for atherogenesis and late failures of
      arterial grafts at these sites.

PMID- 8268586
TI  - Modulation of myofibroblast proliferation by vascular prosthesis biomechanics.
AB  - Cyclic deformation in vitro modulates smooth muscle cell proliferation. Different
      degrees of cell deformation occur in vivo on grafts of different compliance. This
      study evaluates the influence of prosthetic biomechanics on cell proliferation.
      Two types of composite 80% bioresorbable PG910/20% polypropylene (PP) aortic
      grafts differing only in the elasticity of the PP were implanted into rabbits.
      After PG910 resorption, prosthetic biomechanics were determined by PP (%
      elongation: Group 1, 101 +/- 6 versus Group 2, 63 +/- 4). Killing was performed
      at 1, 2, 3, and 6 months, and patency, dynamic compliance, mitotic index (MI),
      and inner capsule thickness (ICT) were determined. Initially all parameters were
      identical. After PG910 resorption (1-2 months), significant differences were
      seen. At late analysis, Group 1 MI was significantly greater than Group 2 (3
      months: 4.67 +/- 2.5 versus 3.11 +/- 2.5 [p < 0.02]; 6 months: 4.11 +/- 2.3
      versus 2.67 +/- 0.9 [p < 0.005]). Inner capsule thickness in Group 1 was also
      significantly greater than Group 2 (3 months: 219 +/- 20 versus 129 +/- 40 [p <
      0.05]; 6 months: 220 +/- 50 versus 130 +/- 40 [p < 0.05]). Dynamic compliance
      differed at 2 months (p = 0.057). Patency was worse in Group 1 (p = NS). In vivo
      cellular proliferative activity is directly related to mural cyclic deformation
      induced by altered biomechanical graft characteristics.

PMID- 8268587
TI  - An in vitro endothelialized compliant vascular graft minimizes anastomotic
      hyperplasia.
AB  - The authors developed a hybrid vascular graft consisting of three components: a
      polyurethane (PU) graft (internal diameter = 3 mm; length: 5 cm) with a
      compliance similar to that of natural arteries; an artificial basement membrane
      composed of a complex gel of Type I collagen and dermatan sulfate; and an
      autogenous endothelial cell (EC) monolayer constructed before implantation. As a
      continuation of their previous study that focused on antithrombogenicity for as
      long as 1 month after implantation, the authors evaluated the antihyperplastic
      characteristics of their hybrid vascular graft for longer implantation periods.
      The hybrid grafts were implanted bilaterally into carotid arteries of dogs
      without anticoagulant or anti-platelet agents. The implantation period ranged
      from 6 to 26 weeks. The overall patency rate observed in this study was 70%.
      Histologic evaluation of grafts revealed that luminal surfaces of the arteries
      and grafts joined uniformly and smoothly. The mean initimal thickness of grafts
      was approximately 80 microns at 12 weeks; there was no statistically significant
      difference in the thickness between portions of the graft. Little additional
      increase was observed at 26 weeks. The intimal thickness of adjacent arteries was
      small. Thus, anastomotic hyperplasia was considered minimized. These encouraging
      results were explained in terms of synergistic activities of the compliant PU
      graft and durable EC monolayer as follows. The PU graft, which was fabricated to
      have the same compliance as that of natural arteries, minimized the compliance
      mismatch at the anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268588
TI  - Differentiated biocompatible design of luminal and outer graft surfaces.
      Photocurable extracellular matrices, fabrication, and cellular response.
AB  - Differentiated biocompatible design of luminal and outer graft surfaces may lead
      to successful healing of vascular grafts. Non-cellular adhesion characteristics
      are required for a luminal surface, whereas enhanced cell adhesion and migration
      are desired for an outer surface. We molecularly designed photocurable
      extracellular matrices (ECMs). Photocurable chondroitin sulfate (CS) was prepared
      for the luminal surface and photocurable gelatin for the outer surface. Both were
      partially derivatized with photodimerizable groups such as cinnamate and
      coumarin. These ECMs were converted to produce water insoluble gels upon
      ultraviolet irradiation. In vitro study showed that platelet adhesion on the
      photogelled CS was significantly reduced, whereas endothelial cells adhered well
      to the photogelled gelatin. These materials were individually coated and
      photogelled onto respective surfaces of knitted Dacron grafts (internal diameter
      5 mm, length 5 cm). The ECM coated grafts were implanted into the abdominal
      aortae of dogs. During acute phase implantation for up to 1 week, minimized cell
      adhesion was observed on the luminal surface where the photogelled CS had
      provided a uniform cover, and enhanced tissue ingrowth was noted at the outer
      surface. However, some thrombi were formed, probably because of incomplete
      coating of, or cracks in, the photogelled CS. Although the molecularly designed
      ECMs and their in vitro performance appeared to follow our concept, further
      improvements in coating technique and molecular design of ECMs are needed for
      better in vivo performance. This may result in enhanced tissue regeneration, as
      well as a high patency rate.

PMID- 8268589
TI  - Development of a chronic endothelialized transcatheter implantable intra-aortic
      graft.
AB  - The authors developed a new intraluminal aortic prosthesis (IA graft) for
      internal obliteration of Stanford type B dissection. The newly devised
      intraluminal aortic graft is a self-expandable metallic stent (Gianturco stent)
      outer-jacketed with a thin open-cell structured microporous film made of
      segmental polyurethane (0.2 mm thick, 0.1 mm pore size). Through the femoral
      artery, the intraluminal aortic grafts (14-20 mm diameter-, 4 cm long) were
      inserted into a 12 Fr catheter sheath by compression, were implanted into the
      descending thoracic aortas of five mongrel dogs; they were removed at the
      projected times of death ranging from 1 to 6 months after implantation.
      Histopathologic examination revealed that an elastic fiber layer had regenerated
      and that on the inner surface of the graft adherent and proliferating endothelial
      cells were observed, even at 1 month after graft implantation. Complete
      epithelialization was observed over the entire inner surface of the graft within
      4 months after implantation. This healing process suggests that the intraluminal
      aortic graft is highly biocompatible and might be stable in chronic use after the
      obliteration of acute Stanford type B dissections.

PMID- 8268590
TI  - Six year experience with wrinkled ePTFE vascular prostheses for arteriosclerosis
      obliterans.
AB  - From November 1986 to January 1993, 97 wrinkled ePTFE prosthetic vascular grafts
      were implanted in 90 peripheral arterial reconstructions for 87 patients with
      arteriosclerosis obliterans (ASO) (79 men and 8 women). Grafts used in this
      series were 54 Vitagraft and 33 Technograft. Initial results for a period of as
      long as 6 years are summarized here. Forty-four (45.3%) grafts were implanted
      anatomically, and the remaining were extra-anatomically routed. The mean age of
      patients in the anatomic bypass group was 64.7 years, and that of patients in the
      other group was 71.4 years. Twenty-three (43.3%) grafts in the extra-anatomic
      group were anastomosed sequentially. Mean follow-up periods for each group were
      32.4 months and 30.9 months, respectively. None of nine late deaths during the
      follow-up period was graft related. There was one primary obstruction in the
      anatomic group; in the extra-anatomic groups, primary graft occlusion occurred in
      four grafts. In addition, one perigraft seroma and one pseudoaneurysm requiring
      surgical repair were seen. Cumulative event free ratio for this group was 80.8%
      at 72 months. These results reveal that the wrinkled ePTFE graft is clinically
      applicable to arterial reconstruction for ASO with satisfactory long-term
      patency, even in extra anatomic sequential bypasses.

PMID- 8268591
TI  - A compliant Corethane/Dacron composite vascular prosthesis. Comparison with 4-mm
      ePTFE grafts in a canine model.
AB  - We have developed a composite vascular prosthesis with the inner blood
      interfacing layer made of a porous elastomeric membrane of spun Corethane fibers
      (10-15 microns in diameter, pore size 30-60 microns) impregnated with a gelatin
      heparin complex and an outer soft tissue interfacing warp knitted Dacron sheath.
      Forty-eight Corethane/Dacron composite (CDC) vascular grafts, 4 mm in diameter
      and 5 cm in length, and 48 expanded polytetrafluoroethylene (ePTFE) vascular
      grafts of similar size were implanted bilaterally as end to end interposition
      grafts on opposite sides in the carotid and femoral arteries in dogs on low dose
      (162 mg/day) aspirin. Patency at 3 months was 37/48 (77%) for the ePTFE grafts
      and 44/48 (91.7%) for the CDC grafts. Fisher's exact test (two-tailed comparison)
      indicates the probability of superior CDC graft patency to be 95.5%. In the seven
      pairs of grafts in which one graft was occluded and the contralateral graft of
      another type was patent, the CDC graft was patent and the ePTFE graft was
      occluded in every instance. Explant histology and scanning electron microscopy
      showed greater collagenization, less residual platelet-fibrin and red blood cell
      deposits, and more frequent mid-graft endothelialization in the CDC grafts than
      in the ePTFE grafts.

PMID- 8268592
TI  - Comparison of the cross-linking characteristics of porcine heart valves fixed
      with glutaraldehyde or epoxy compounds.
AB  - The concerns about currently available bioprosthetic heart valves are
      calcification, long-term durability, and functional and hemodynamic performance.
      These concerns are all more or less related to the cross-linking reagents,
      glutaraldehyde or formaldehyde, used in fixing bioprostheses. To address these
      concerns, the authors undertook the development of a porcine heart valve cross
      linked with an epoxy compound. This study compared the cross-linking
      characteristics, shrink temperature, and moisture content of porcine heart valves
      fixed with epoxy compounds or glutaraldehyde. Two types of epoxy compounds,
      Denacol EX-313 and EX-810, or a 0.625% glutaraldehyde were used to fix the
      porcine aortic valves procured from a slaughter house. Samples of each group were
      removed at various elapsed fixation times. The shrink temperature and moisture
      content of the valvular leaflet and distinct layers of aortic wall of each sample
      were measured. Fresh porcine aortic valve was used as a control. It was found
      that the shrink temperature of the glutaraldehyde leaflet was the highest,
      whereas the moisture content of the EX-313 leaflet was the greatest among the
      three test groups. No significant difference in shrink temperature was observed
      among the epoxy compound fixed inner, middle, outer, and entire aortic walls.
      This implied that the cross-linking density of the epoxy compound valve was
      uniform throughout the entire aortic wall. The same also was observed for the
      glutaraldehyde fixed aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268593
TI  - In vivo canine studies of a Sinkhole valve and vascular graft coated with
      biocompatible PU-PEO-SO3.
AB  - PU-PEO-SO3 was applied as a coating material over a newly designed Sinkhole
      bileaflet PU heart valve and a porous PU vascular graft. Performance and
      biocompatibility were evaluated using an in vivo canine shunt system between the
      right ventricle and pulmonary artery. The survival periods in three implantations
      were 14, 24, and 39 days, during which no mechanical failure occurred in any
      Sinkhole valve or vascular graft. Scanning electron microscopy (SEM) studies
      demonstrated much less platelet adhesion and thrombus formation on PU-PEO-SO3
      grafts than on PU vascular grafts. Cracks in the valve leaflet were occasionally
      observed on PU surfaces, but not on PU-PEO-SO3. After a 39 day implantation,
      calcium deposition on vascular grafts was decreased as compared with valve
      leaflets, and calcification on PU-PEO-SO3 was much lower than on PU. These
      results suggest that Sinkhole valves and vascular grafts are promising, and PU
      PEO-SO3 as a coating material is more blood compatible, biostable, and
      calcification resistant in vivo than in untreated PU.

PMID- 8268594
TI  - A novel surface photo-graft polymerization method for fabricated devices.
AB  - This paper presents a new photo-graft polymerization method that permits surface
      modification of complex shaped devices. The principle is based on photochemistry
      of the dithiocarbamate group, as a polymerization initiator-transfer agent
      terminator (iniferter), which is capable of photochemical dissociation into a
      radical pair. The procedure is as follows: first, coating of a photosensitive
      polymer on a substrate, and subsequent ultraviolet (UV) light irradiation in the
      presence of a monomer. The photosensitive polymer prepared was a radical
      copolymer of styrene and vinylbenzyl N,N-diethyldithiocarbamate. Surface graft
      polymerization of a water soluble monomer (N,N-dimethylacrylamide) on
      poly(ethylene terephthalate) pre-coated with the photosensitive polymer was
      achieved. Because the photopolymerization proceeded via a living radical
      polymerization, the control of molecular weight of the grafted polymer was
      feasible. This was quantitatively observed by graft polymerization on a quartz
      crystal microbalance (QCM) that can detect the weight increase with the
      sensitivity of ng-order. Two-dimensional patterning of cultured cells was
      demonstrated to show how surface grafted polymerization is limited on UV light
      irradiation portions with dimensionally micron order precision.

PMID- 8268595
TI  - Effects of nafamostat mesilate on platelets and coagulofibrinolysis during
      cardiopulmonary bypass surgery.
AB  - The effect of nafamostat mesilate (FUT-175) on platelet membrane glycoproteins
      and the coagulofibrinolytic system were analyzed. Twenty-five patients undergoing
      aorto-coronary bypass surgery were randomly distributed into an FUT treated group
      and a control group. In the control group, anticoagulation was achieved with
      sodium heparin (3 mg/kg) immediately before cardiopulmonary bypass (CPB). In the
      FUT treated group, in addition to the usual treatment with heparin, FUT-175 was
      infused continuously at a rate of 2 mg/kg/hr. In the control group, alpha 2
      plasmin inhibitor/plasmin complex (PIC) and fibrinogen/fibrin degradation
      products (FDP) D-dimer increased significantly during CPB, reaching 6.1 +/- 5.1
      micrograms/ml and 576 +/- 200 ng/ml, respectively, at 60 min of CPB. PIC and FDP
      D-dimer remained significantly lower in the FUT treated group than in the control
      group. GPIb on platelets decreased significantly in both groups, but remained
      higher in the FUT treated group (81 +/- 5% vs. 56 +/- 21% at 60 min of CPB, P <
      0.01). There were no significant changes in GPIIb/IIIa on platelets throughout
      the procedure in either group. Blood loss after CPB was significantly lower in
      the FUT treated group than in the control group (778 +/- 277 ml vs. 1,342 +/- 426
      ml, P < 0.01). The authors conclude that FUT-175 improves hemostasis after CPB,
      not only by inhibiting fibrinolysis, but also by preserving platelet GPIb during
      CPB.

PMID- 8268596
TI  - Platelet dysfunction during cardiopulmonary bypass surgery. With special
      reference to platelet membrane glycoproteins.
AB  - Changes in platelet membrane glycoproteins (GPIb, GPIIb/IIIa, and GMP-140) were
      evaluated using flow cytometry after binding with monoclonal antibodies in 22
      adult patients undergoing cardiopulmonary bypass (CPB) surgery. The amount of
      GPIb on platelets decreased significantly during CPB, reaching a minimum level of
      64 +/- 26% of the pre CPB value at 120 min of CPB. There was no significant
      change in the amount of GPIIb/IIIa on platelets. In accordance with these
      changes, ristocetin induced agglutination decreased to 56.7 +/- 16.2% of the pre
      CPB value during CPB. However, there were no significant changes in ADP and
      collagen induced aggregation throughout the procedure. The number of the
      activated platelets expressing GMP-140 on their surfaces increased significantly
      during CPB. There was an upper limit to the amount of GMP-140 expression on each
      platelet in the circulating blood, suggesting that excessively activated
      platelets are removed from the circulation. The authors conclude that CPB reduces
      the amount of GPIb on platelets, which results in platelet dysfunction. In
      addition, removal of excessively activated platelets from the circulation may
      lead to thrombocytopenia after CPB.

PMID- 8268597
TI  - A hybrid artificial esophagus using cultured human esophageal epithelial cells.
AB  - It is important to cover an artificial esophagus with epithelium to prevent
      stenosis and reinforce the lumen. We examined the possibility of
      epithelialization of the surface of a latissimus dorsi muscle of athymic mice
      using cultured human esophageal epithelial cells. Normal human esophageal mucosa
      (0.5 cm2) was processed from specimens resected from patients with esophageal
      cancer, and epithelial cells were cultured on collagen gel in a culture dish (30
      cm2) for about 10 days. The collagen sheets with cultured cells were transplanted
      onto the surface of latissimus dorsi muscles of 16 athymic mice. Four animals
      were killed 4, 8, 12, and 16 days after transplantation, and the transplanted
      collagen sheets were studied histologically. Cultured sheets had attached to the
      muscle in all 16 athymic mice. By 16 days, neovascularization in the collagen
      layer was observed and the epithelial cell layer was similar to normal human
      esophageal epithelium. This study suggests that epithelialization on latissimus
      dorsi muscle is possible using cultured human esophageal epithelial cells, and
      this could lead to the practical use of a hybrid artificial esophagus consisting
      of a latissimus dorsi muscle tube with its inner side epithelialized by cultured
      cells.

PMID- 8268598
TI  - A new method for continuous measurement of platelet adhesion under flow
      conditions.
AB  - Platelet adhesion to the subendothelial tissue or biomaterial surface is an
      initial step in the formation of the hemostatic plug or thrombus. To clarify the
      mechanism of platelet adhesion in vivo, a simple and reproducible method for
      quantitation of platelet adhesion under flow conditions is required. In this
      study, a mechanical device for continuous recording of platelet adhesion under
      flow conditions using a quartz crystal microbalance was developed, an extremely
      sensitive sensor capable of measuring mass changes in the nanogram range. The
      relationship between surface mass change (delta W) and resonant frequency change
      (delta f) for pie-zoelectric crystals is given by the Sauerbrey equation: delta f
      = -fo2 delta W/NA pi (fo; fundamental frequency (5MHz) A; the area of quartz
      plate undergoing oscillation N; frequency constant for AT-cut quartz crystal pi;
      density of quartz crystal). Although the perfusion of buffer solution alone or
      addition of washed red cell suspension (Ht 30%) and formaldehyde-fixed platelets
      have no effect on delta f, addition of washed platelets in the presence of red
      cells caused an increase in delta f. To confirm that the increase in delta f
      results from platelet adhesion to the material surface, adherent and subsequently
      aggregated platelets were visualized by fluorescence microscopy using fluorescein
      isothiocyanate labeled antiplatelet membrane glycoprotein Ib monoclonal antibody.
      There was a good correlation between the increase in delta f and the extent of
      platelet adhesion and subsequent aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268599
TI  - In vitro reconstruction of hybrid vascular tissue. Hierarchic and oriented cell
      layers.
AB  - Hybrid vascular tissue was hierarchically reconstructed in vitro. A hybrid medial
      layer composed of type I collagen gel, in which SMCs derived from a mongrel dog
      were embedded, was formed on the inner surface of a compliant porous polyurethane
      graft (internal diameter = 3 mm). Endothelial cells (ECs) from the same animal
      were seeded and cultured on the hybrid media to build an intimal layer.
      Subsequently, hierarchically structured grafts constructed in this manner were
      subjected to pulsatile flow (flow rate: 8.5 ml/min; frequency: 60 rpm; amplitude:
      5% of graft outer diameter) of culture medium (Medium 199 supplemented with 20%
      fetal calf serum). After stress loading for as long as 10 days, tissues were
      morphologically investigated with a light microscope and a scanning electron
      microscope. Inner surfaces of the hybrid tissues were covered with EC monolayers
      that aligned along the direction of the flow (i.e., longitudinally). However,
      SMCs beneath the intima aligned in the circumferential direction. These cellular
      orientations resembled those in native muscular arteries. The pulsatile stress
      loaded hybrid tissue mimicked native muscular arteries with respect to hierarchic
      structure and cellular orientation. In vitro mechanical stress loading on a
      hybrid graft might provide a high degree of integrity in terms of tissue
      structure that promises high tolerance toward hydrodynamic stress and regulation
      of vasomotor tone upon implantation.

PMID- 8268600
TI  - Continuous ambulatory peritoneal dialysis with a high flux membrane. A
      preliminary report.
AB  - The standard peritoneal equilibration test (PET) was performed in 66 patients on
      continuous ambulatory peritoneal dialysis (CAPD). Patients were classified as low
      (n = 5), low average (n = 22), high average (n = 27), and high (n = 12)
      transporters based on the dialysate/plasma creatinine (D/P Cr) after 4 hr dwells.
      After an average time interval of 14 months on CAPD, indices of dialysis adequacy
      and nutrition were assessed. Based on monitoring of patient chemistries and drain
      volumes, peritoneal transport was considered stable during the interval.
      Instilled volumes and exchange tonicity were individualized in each patient to
      achieve combined renal and dialysis weekly creatinine clearance and KT/V urea
      that were not significantly different between groups. High transporters had
      significantly (p < 0.05) lower mean serum albumin, net protein catabolic rate
      (nPCR), lean body mass calculated from creatinine kinetics, and daily creatinine
      production (and presumably lower muscle mass), and higher albumin clearances
      compared to one or more lower transport groups. In conclusion, we hypothesize
      that high transporters are prone to protein malnutrition related to increased
      dialysate protein losses, and perhaps suppression of appetite, with increased use
      of hypertonic exchanges. High transporters are candidates for protein
      supplementation on CAPD or transfer to nightly intermittent peritoneal dialysis
      where short cycles provide more ultrafiltration with less glucose absorption.

PMID- 8268601
TI  - Comparison of binding by concentrated peritoneal dialysate and serum.
AB  - Major advances in dialysis therapy have occurred over the last decade, yet
      various abnormalities persist in end-stage renal disease (ESRD) patients. The
      etiology of these residual defects remains largely unknown. We are currently
      testing the hypothesis that some of these abnormalities are due to retention of
      small molecular weight, protein bound toxins, which are poorly dialyzable. We
      sought an alternative to blood as a source of bound toxins. Spent peritoneal
      dialysate (PD) was tested as a source. With use of a series of filtration
      devices, PD albumin content was increased about 35-fold. Evidence of bound
      ligands was shown by two methods. Salicylate binding by patients' sera and
      concentrated PD (n = 8) were markedly reduced, unbound salicylate being 14.9 +/-
      5.1% (SD) and 15.8 +/- 4.9% at albumin concentrations of 3.30 +/- 1.04 and 3.23
      +/- 0.84 g/dl. Serum from eight normal subjects, diluted to 2.95 g/dl albumin,
      had 7.4 +/- 1.1% unbound salicylate. HPLC analysis of deproteinized concentrated
      dialysate was compared to ultrafiltrates of the same fluid. Numerous bound peaks
      were seen, particularly in the late eluting peaks. Spent PD is a rich source of
      protein bound ligands for further study.

PMID- 8268602
TI  - A regional blood circulation alternative to in-series two compartment urea
      kinetic modeling.
AB  - Assuming that the clearance of urea from total body water (TBW) is flow limited,
      the authors developed a parallel flow model using physiologic data. Organ systems
      with a blood flow to water volume ratio of greater than 0.2 min-1 were allocated
      to the high flow system. Remaining organs were represented in the low flow
      system. In end-stage renal disease patients with minimal renal blood flow, the
      high flow system contained 20% TBW and received 70% of the systemic blood flow.
      The authors used this flow heterogeneity to predict the post-dialysis urea
      rebound (R) in 12 patients after 1 hr of hemodialysis. Dialyzer clearance was 248
      +/- 14.5 ml/min (mean +/- SEM) Access recirculation was obviated by returning
      cleared blood into a central vein. In these patients, R at 1, 3, 5, 7, 10, and 15
      minutes. after slowing dialyzer blood flow (Qb) from 383 +/- 18 to 50 ml/min was
      3.8 +/- 2.9, 6.2 +/- 3.4, 7.6 +/- 3.1, 8.8 +/- 3.9, 9.0 +/- 4.1, and 9.9 +/-
      4.4%, respectively. CO and QAc were modeled with values of 5.5 and 0.5 L/min,
      respectively. The modeled TBW was 35 L. Total body water derived by nomogram was
      38.1 +/- 2.0 L. Our results suggest that the parallel-flow model for urea
      transport can be used to explain the amount and time course of post dialysis R on
      a physiologic basis.

PMID- 8268603
TI  - Erythropoietin with oral iron in peritoneal and hemodialysis patients. A
      comparison in an inner city population.
AB  - Studies on the comparative efficacy of erythropoietin (rHuEPO) in chronic
      hemodialysis (HD) and peritoneal dialysis (PD) patients are scarce. The authors
      compared the use of rHuEPO in 74 stable patients on hemodialysis with 24 on
      chronic peritoneal dialysis. All patients were on oral iron supplements. In PD
      patients, hematocrits were 23.1 and 30.1%, rHuEPO dose 80.9 and 89.0 U/kg/wk,
      whereas in HD patients, hematocrits were 21.2 and 27.5 and rHuEPO dose was 140.2
      and 165.0 U/kg/wk at initiation and 6 months, respectively. Serum iron and
      transferrin saturations were unchanged in peritoneal, but decreased in
      hemodialysis patients on rHuEPO therapy. These findings suggest that rHuEPO is
      more effective in peritoneal dialysis patients than in hemodialysis patients
      receiving oral iron. The improved efficacy of rHuEPO in peritoneal dialysis may
      be due to decreased blood loss, subcutaneous administration, or better removal of
      inhibitors of erythropoiesis. Peritoneal dialysis may be more cost effective and
      desirable than hemodialysis for rHuEPO dependent or resistant patients.

PMID- 8268604
TI  - Suppression of thrombin formation during hemodialysis with triglyceride.
AB  - Effect of blood-air contact in the venous line air-trap chamber on blood clotting
      was studied. Fourteen chronic hemodialysis patients (six men, eight women; mean
      age, 49 years) with elevation of thrombin-antithrombin III were studied. To
      prevent blood-air contact, triglyceride (NOF-005) was floated over the blood in
      the chamber. Control hemodialysis was performed for 4 weeks and hemodialysis
      using NOF-005 followed for the next 4 weeks. Clot formation in the circuit was
      examined after each hemodialysis and clotting factors including thrombin
      antithrombin III, FXII Antigen, vWF Antigen, PF4 and beta-thromboglobulin were
      measured before and after the last hemodialysis of each control and NOF-005
      hemodialysis. Clotting in the chamber was improved when NOF-005 was used.
      Thrombin-antithrombin III increase during hemodialysis was suppressed to about
      30% of control values by using NOF-005. blood-air contact seems to promote
      thrombin generation and accelerate clot formation.

PMID- 8268605
TI  - Monitoring hemodialysis changes with bioimpedance. What do we really measure?
AB  - Changes in electrical resistance (delta R), water (delta H2O), and blood
      variables (Na+, K+, Cl-, protein [Pr], osmolality [Osmo], hemoglobin [Hb], and
      hematocrit [Hct]) were monitored during hemodialysis in 20 subjects. Average
      delta H2O was 1.69 +/- 0.91 liters. Blood, R, and circumferences (C) were
      measured for the upper limb (UL), lower limb (LL), and total body (TB) before,
      midway, and at the end of dialysis. Segmental volumes (V) and specific
      resistivity (rho) were computed. delta Hct and delta Pr were stronger predictors
      of delta H2O than delta R. Forward stepwise regression analysis using delta R at
      5, 50, and 548 kHz, delta Pr, and delta Hct showed that delta Hct and delta Pr
      alone accounted for 77% of the variance in delta TBW. Adding delta R increased
      this at most to 81%. Both the UL and LL had significant increases in rho. The
      volumetric change of the UL was nonsignificant, whereas that of the LL accounted
      for over one half of the delta H2O. Single frequency bioimpedance cannot be used
      to monitor dialytic delta H2O unless one accounts for fluid composition changes.
      Monitoring bioimpedance changes over only a single body segment is also
      questioned.

PMID- 8268606
TI  - Formaldehyde, sodium hypochlorite, and metabisulphite are equally effective as
      sterilants for central delivery systems.
AB  - Sterilants are used to disinfect reverse osmosis (RO) thin film composite
      membranes or peripheral loop water delivery systems. Formaldehyde (4.0%
      weight/volume) and metabisulphite (1.0%) were used to sterilize the RO and
      peripheral loop, and sodium hypochlorite (0.5%) was used to sterilize the
      peripheral loop with only acid/alkaline treatment of the RO; each sterilant was
      evaluated for 4 months. Sanitization at the machine was with sodium hypochlorite
      or glutaraldehyde. Quantitative RO processed water (weekly) and dialysate (4-6
      from each station during the period of each sterilant) cultures were obtained.
      AAMI standards were used (< 200 CFU/ml RO water; < 2,000 CFU/ml dialysate).
      Bacterial growth exceeded Association for the Advancement of Medical
      Instrumentation (AAMI) limits in 16% of RO water and 4.7% of dialysate samples,
      but repeat cultures invariably failed to confirm initial abnormal results. Chi
      square analysis showed no differences among sterilants. No difference among
      sterilants was noted in arithmetic or log10 mean colony counts. Sporadic low
      level gram positive and gram negative organism growth occurred with all
      sterilants. Continued "sterility" that met AAMI standards was obtained for 1
      year, first with metabisulphite and then with acid/alkaline RO and sodium
      hypochlorite loop treatment. It is concluded that all three sterilants are
      effective for disinfection of hemodialysis delivery systems. Sodium hypochlorite
      is recommended because of its safety advantages and readily available test of
      adequate removal.

PMID- 8268607
TI  - Effect of aging on the body composition of dialyzed subjects. Comparison with
      normal subjects.
AB  - A bioimpedance analyzer (BIA-CHIP; Akern RJL System) was applied to 366 normal
      subjects (171 men and 195 women). Each gender group was divided into eight
      groups, according to age: 20-29 years; 30-39 years; 40-49 years; 50-59 years; 60
      69 years; 70-79 years; 80-89 years; and 90-95 years. The same was done with 44
      hemodialysis patients (22 men, 22 women), each being evaluated 15 times over a
      period of 5 years: these were divided into seven groups (seven, because no
      patient was older than 89) using the same criteria. For each subject, 23
      parameters were determined: 5 directly measured (height, weight, resistance,
      reactance, phase angle) and the others (fat and lean mass, body water, body cell
      mass, extra and intracellular water, etc.) from appropriate equations. Twenty
      four thousand data points were collected and served to form a data bank. Men and
      women on hemodialysis showed different effects of aging: women normalized their
      BC at an age > 70 years, whereas men continued to have a muscle mass lower than
      that of normal subjects until the age of 80. A computerized program (Nutritio)
      permits fast and reliable evaluation of the nutritional status of hemodialysis
      patients, each subject being compared with both the similarly aged population
      (dialyzed or not) or with his or her own data, obtained over time.

PMID- 8268608
TI  - Relationship of protein catabolic rate or Kt/V with morbidity.
AB  - The authors investigated the influence of Kt/V and protein catabolic rate (PCR)
      on dialysis failure for 689 hemodialysis (HD) outpatients treated at the seven
      dialysis facilities in Aichi Prefecture, Japan. Dialysis failure was defined as
      death or hospitalization for reasons other than blood access, accident, wound, or
      mental disease. Patients were followed for 2 years. The rate of patients who
      developed dialysis failure during the observation period relative to the total
      patient population was defined as the dialysis failure rate. A total of 123
      patients developed dialysis failure, which was fatal in 33 cases. In patients
      with Kt/V values of 1.6 or higher, the mean dialysis failure rate was
      significantly lower at 12.0% than that (19.2%) of patients with Kt/V values
      between 0.8 and 1.6 (p < 0.04). In patients that had PCR values under 0.8
      g/kg/day, the dialysis failure rate was significantly higher at 32.5% than that
      (15.8%) of patients with PCR values between 0.8 and 1.4 g/kg/day (p < 0.0001).

PMID- 8268609
TI  - Automatic continuous venovenous hemodiafiltration in cardiosurgical patients.
AB  - Intermittent substitutive treatments in severely ill patients with acute renal
      failure are difficult or not suitable because of technical problems and/or
      hemodynamic instability. Continuous venovenous hemodiafiltration allows an
      adequate, slow removal of fluid, electrolytes, and waste products by combining
      diffusive and convective solute transport. Eight patients with acute renal
      failure, after cardiovascular surgery and cardiogenic shock, were treated by
      continuous venovenous hemodiafiltration. An automatic system (Equaline System,
      Amicon Division, USA) was employed. Venous accesses (femoral or subclavian) were
      used with double lumen catheters. A polysulfone filter (0.4 m2) was used in the
      study. Blood flow was 30 ml/min and dialysate flow rate 16.6 ml/min. Sterile
      pyrogen-free hemofiltration substitution fluid was used as dialysate. Mean
      duration of treatment was 10.3 +/- 3.2 days. After 72 hours blood urea nitrogen
      levels dropped from 136 +/- 46.13 to 53.5 +/- 12.3 mg/dl and creatinine levels
      dropped from 6.9 +/- 1.7 to 2.6 +/- 0.9 mg/dl. A controlled steady-state was then
      maintained. Mean urea clearance was 21 +/- 5.3 ml/min; mean ultrafiltration rate
      was 20.3 +/- 4.1 L/day. Continuous venovenous hemodiafiltration, with the
      Equaline System, is effective for the clearance of waste products and is able to
      maintain perfect fluid balance in catabolic patients with acute renal failure and
      multiple organ failure.

PMID- 8268610
TI  - Accumulation of a disopyramide metabolite in renal failure.
AB  - Ten hemodialysis (HD) patients with normal liver function received disopyramide
      (DP) therapy in the steady state. DP, mono-N-dealkyldisopyramide (MND) and alpha
      1-acid glycoprotein (AAG) were measured before and after HD. Ten patients with
      normal renal and liver function were selected as controls. The DP concentration
      was 2.08 +/- 0.39 micrograms/ml (mean +/- SD) in the control group, and the pre
      and post HD levels were 2.40 +/- 1.08 micrograms/ml and 1.73 +/- 0.87
      micrograms/ml, respectively, in the HD group. The MND concentration was 0.42 +/-
      0.23 microgram/ml in controls, 1.53 +/- 0.52 micrograms/ml in pre HD and 1.08 +/-
      0.32 microgram/ml in post-HD. Although DP and MND are both classified as small
      molecular weight substances, the average decrease in plasma concentration from
      pre to post HD was under 30% with both agents. The MND/DP ratio in the HD group
      was higher than in controls, but there was no significant difference between pre
      and post HD. The AAG level was 75 +/- 5 mg/dl in controls and 109 +/- 11 mg/dL
      before HD in the HD group (p < 0.001). In conclusion, an MND accumulation was
      observed in HD patients receiving DP therapy. Because the anticholinergic effect
      of MND is 24 times that of DP, MND is thought to contribute in some way to the
      hypoglycemia induced by DP in renal failure.

PMID- 8268611
TI  - Cytosolic ionized magnesium concentration in end-stage renal disease. Effect of
      hemodialysis.
AB  - Chronic renal failure is known to raise serum magnesium concentration. However,
      its effect on intracellular free cytosolic magnesium concentration ([Mg2+]i) has
      not been clearly delineated. Likewise, whereas hemodialysis (HD) lowers serum
      magnesium concentration, its effect on [Mg2+]i is unknown. It should be noted
      that, based on other studies, [Mg2+]i is inversely related to arterial blood
      pressure in the general population. Given the high prevalence of hypertension in
      end-stage renal disease (ESRD), the study of [Mg2+]i in this population is of
      interest. We measured platelet [Mg2+]i in nine ESRD patients, six of whom were
      hypertensive. Samples were obtained from arterial and venous lines at the start
      of an HD session, and from the arterial line at the end of an HD session. Five
      normal volunteers served as controls. [Mg2+]i was measured by spectrofluorometry
      using Mag-fura-2-AM. Serum magnesium and calcium concentrations were determined
      by atomic absorption. Compared with the normal control group, the ESRD patients
      exhibited significantly lower [Mg2+]i but higher serum magnesium concentrations.
      As expected, HD lowered the serum magnesium concentration. However, platelet
      [Mg2+]i was unaffected by either a single passage through the dialyzer or the
      entire dialysis procedure. [Mg2+]i did not correlate with serum magnesium or
      calcium concentrations, nor with the presence or absence of hypertension.

PMID- 8268612
TI  - Maximum ultrafiltration rate in continuous arteriovenous hemofiltration does not
      occur at the lowest level of the ultrafiltrate collection chamber.
AB  - A common assumption is that increasing transmembrane pressure by lowering the
      ultrafiltrate receptacle and the accompanying fluid column should always result
      in increasing ultrafiltration in continuous arteriovenous hemofiltration (CAVH)
      systems. To test this assumption, CAVH circuits were operated in vitro with use
      of a recirculating apparatus with an adjustable elevated reservoir. Hydraulic
      operational characteristics were studied in a variety of CAVH circuits, lowering
      the height of the ultrafiltrate column stepwise until it was at the lowest height
      possible. The results for most experiments performed reveal that ultrafiltration
      rate (UFR) reaches a peak and then declines as the collection receptacle is
      lowered further. There is also a decline in pre-filter blood flow preceding the
      peak in UFR. At lower blood flow, UFR decreases for the same transmembrane
      pressure (TMP). Therefore, as ultrafiltrate pressure is decreased, the effect of
      increased TMP on UFR is opposed by the effect of decreased blood flow, which
      decreases UFR. The implication of this in clinical medicine is that one may need
      to empirically test UFR in a CAVH system in positions other than the very lowest
      position.

PMID- 8268613
TI  - A new procedure for the removal of protein bound drugs and toxins.
AB  - To extend the applicability of dialysis to the removal of albumin bound toxins, a
      new dialysis procedure was developed. A double sided albumin impregnated high
      flux polysulfon dialyzer was used together with a closed loop dialysate
      compartment with an albumin containing dialysate solution, that was purified on
      line in a three step process with a charcoal and resin adsorbent, and another
      dialyzer for a normal dialysis or filtration of the albumin containing dialysate
      that was then recycled to the albumin impregnated dialyzer. The system
      effectively removed strongly albumin bound toxins like unconjugated bilirubin or
      free fatty acids from plasma and blood in vitro and in vivo and therefore could
      be considered a possible therapeutic means for the treatment of acute liver
      failure or acute and chronic intoxications with albumin bound toxins, e.g., in
      drug overdose or chronic renal failure.

PMID- 8268614
TI  - Relative blood damage in the three phases of a prosthetic heart valve flow cycle.
AB  - Blood flow through a prosthetic heart valve operating in a ventricular assist
      device can be subdivided into three phases: a) forward flow through an open
      valve, b) rapid valve closure, and c) regurgitant back flow through a closed
      valve. Recent studies of fluid stresses in the Penn State Electric Left
      Ventricular Assist Device (PS LVAD) operating under physiologic conditions
      indicate that Reynolds stresses of possibly hemolytic magnitude may exist in the
      valve area. Although several studies have been made of the fluid stresses seen in
      forward flow through an open valve, few have looked at valve closure or backflow,
      and none have related these stresses directly to blood damage. In this study,
      novel in vitro blood flow loops were developed to allow for the separate analysis
      of the three flow phases of a Bjork-Shiley monostrut Delrin disk valve operating
      in a PS LVAD. Forward flow through fully open aortic and mitral valves and
      backflow through closed valves are studied separately in flow loops driven by a
      roller pump with the LVAD acting as a valve housing and compliance vessel. Valve
      closure is investigated with a PS LVAD operating in a low volume mock circulatory
      loop characterized by cavitation potential through stroboscopic videography of
      this mock loop, using saline as the working fluid. Rate of hemolysis,
      characterized by the index of hemolysis, IH, is determined for each of the three
      flow loops charged with fresh porcine blood.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268615
TI  - Intraoperative epicardial echo/Doppler evaluation of a stentless, chordally
      supported quadricusp mitral bioprosthesis.
AB  - The authors have developed a stentless, chordally supported quadricusp mitral
      bioprosthesis made from bovine pericardium. A large anterior, two commissural,
      and one posterior cusp all have straight hinge lines and avoid the excessive
      flexion stress of stent supported valves. The chordal support is concentrated in
      two flaps for suture to the papillary muscles. Previous in vitro and animal
      studies demonstrated its superior hemodynamic, biomechanical, and biocompatible
      behavior over commercial valve bioprostheses. In this study, we further evaluated
      its in vivo performance by intraoperative epicardial Echo/Doppler immediately
      after the bioprosthesis was implanted in 10 sheep. In all 10 sheep, Echo showed
      the valves were similar to native mitral valves in both anatomic appearance and
      movement. Mitral annular motion and annular-papillary muscle integrity were
      preserved. In systole, the valves closed competently with chordae moving upward
      and straightening; in diastole, the valves opened wide with chordae moving
      downward and relaxing. Color and pulsed Doppler showed no signs of stenosis or
      regurgitation. In conclusion, the new mitral bioprosthesis provide excellent in
      vivo performance that mimics the native mitral valve. Intraoperative
      echocardiography is recommended after mitral valve replacement with such valves.

PMID- 8268616
TI  - Fluorescent image tracking velocimetry of the Nimbus AxiPump.
AB  - High shear rates and extended residence times causing hemolysis and platelet
      activation can develop in an assist pump or cannula when inferior flow conditions
      exist. The high volume output of a miniature axial flow pump presents challenges
      in avoiding these adverse conditions. To assess the hemodynamics within the
      continuous flow Nimbus Axi-Pump, vector flow fields inside a translucent inflow
      cannula and a modified 12 mm AxiPump were mapped. Fluorescent image tracking
      velocimetry was used to track the motion of neutrally buoyant fluorescent
      particles (30 microns) using pulsed laser light, high resolution video cameras,
      and computer image analysis. An acrylic pump housing and cannula were integrated
      into a mock circulatory loop filled with a Newtonian, optically clear blood
      analog fluid. The flow parameters were controlled to yield known, physiologic
      loading conditions, including varying degrees of pulsatility. Cannula flow
      visualization results exhibited critical recirculation patterns at the bend.
      These results will be used to further optimize the design of the inflow. Particle
      impact was seen at the pump inlet in the inducer region of the rotor. Very good
      attachment of flow from the rotor to stator was observed when the pump operated
      at normal operating speeds. Intermittent regurgitant flow fields were evident in
      the presence of increased pulsatility and low pump speed. These results have lead
      to improvements in impeller design and speed control criteria to avoid potential
      deleterious flows.

PMID- 8268617
TI  - An implantable left ventricular assist system with an electrical impedance
      monitoring and control system.
AB  - The authors developed an implantable left ventricular assist system (LVAS) for
      bridge to transplant of rather small sized adults. The pump was made of segmented
      polyether polyurethane and was 86 mm in diameter, 50 mm in height, with a 70 ml
      nominal stroke volume. A percutaneous drive line was connected with an external
      pneumatic control drive unit (CDU). In chronic animal experiments using 11 adult
      goats, the pump was installed between the LV apex and the descending aorta and
      was placed in the abdominal wall. Five goats were killed after 4 to 14 weeks
      while in good physical condition, and one is ongoing. There were no prominent
      thromboembolic symptoms despite no anti-thrombogenic agent being used. The new
      electrical impedance-based monitoring and control system (Z system) was installed
      in the CDU. In this Z system, automatic calibration was performed periodically
      for several seconds while the drive condition was changed to ensure full-fill of
      the blood pump. The full-fill to full-empty drive was well controlled by this Z
      system. In conclusion, the new Z system is practical and useful for monitoring
      and control of an implantable pump, giving this LVAS a promising place in
      clinical use.

PMID- 8268618
TI  - A superconductive electromagnetic pump without any mechanical moving parts.
AB  - Mechanical reliability is one of the main obstacles to long-term performance of
      an artificial heart. To solve this problem a superconductive electromagnetic pump
      was developed. Two concentric cone-shaped cylinders serve as the pump housings
      and electrodes. As a current passes through the blood between the inner and outer
      housings, the blood rotates under the action of a superconductive magnetic field.
      Therefore, this is a rotary pump without a rotor or any mechanical moving parts.
      The device was tested in a super-conductive magnetic field with 7 Tesla. By 5 V,
      and 1 A, a 0.9% saline flow of approximately 1 L/min, and 10 mm H2O was obtained.
      For further development, a stronger magnetic field with ca. 20 Tesla is
      desirable. Contrary to traditional thought, blood and saline have almost the same
      conductibility as any other conductors. For blood damage testing, fresh porcine
      blood was used. The circulation was maintained by an impeller pump, with the
      electromagnetic pump serving only as electrodes. Comparing the first and second
      periods of testing with and without a current of 1 A, the difference in
      hematologic variations evaluated the blood damage by the electric current passing
      directly through the blood. Results indicated that the electric current causes no
      serious blood damage.

PMID- 8268619
TI  - Venovenous single lumen cannula extracorporeal lung support in neonates. A five
      year experience.
AB  - The authors have developed a venovenous extracorporeal lung support technique
      with an original single lumen cannula to avoid the carotid ligation of
      venoarterial extracorporeal membrane oxygenation (ECMO). During a 5 year period,
      the authors have used the technique in 107 neonates (weight: 3.045 +/- 0.6 1 kg;
      gestational age: 38.1 +/- 2.2 weeks). All of the neonates had severe respiratory
      failure despite maximal conventional treatment and the same indications as those
      for ECMO. The venovenous technique associates extracorporeal CO2 removal and
      apneic oxygenation. The system includes a single lumen cannula, an alternating
      clamp that generates a tidal flow, and an original non-occlusive roller pump that
      avoids the use of a venous bladder. The PaCO2 was normal (34.6 +/- 3.9 mmHg) with
      a blood flow of 40-50% of the total cardiac output. Under apneic oxygenation,
      PaO2 improved rapidly, allowing a decrease in FiO2 and mean airway pressure,
      minimizing barotrauma. The mean duration of bypass was 117.8 +/- 83.9 hr, and 91
      of the 107 (85%) neonates were weaned from AREC. The technical complications were
      less important than those associated with venoarterial ECMO. The authors conclude
      that AREC is as effective as venoarterial ECMO and is easier to use.

PMID- 8268620
TI  - Verification testing of the bearings used in the electrohydraulic total
      artificial heart.
AB  - This article reports the verification testing performed on the ball bearings used
      in the electrohydraulic total artificial heart (EHTAH) device. The bearings were
      tested for 70 days under conditions intended to simulate those actually
      experienced by the bearings in the EHTAH device. Vibration analysis to predict
      the condition of the bearings, as well as diagnosis of the wear experienced by
      the bearings, was included in this study. Examination of the bearings using light
      microscopy indicated the presence of wear, and in some instances the contact
      surfaces had undergone temper coloring, a warning sign that hardness of the
      bearing may have been impaired, and that the bearing has experienced a
      temperature excursion. Temper coloring can be caused by too thick a coating of
      grease or by insufficient hydrodynamic film thickness. In this investigation, the
      vibration amplitudes at specific frequencies that correlated with the bearing
      components were monitored for change. From analysis of the vibration spectra, it
      was found that the change in amplitude did not predict the damage incurred by the
      bearings. The type of damage experienced by the bearings is difficult to predict
      using spectral analysis.

PMID- 8268621
TI  - Life testing of implantable batteries for a total artificial heart.
AB  - Although lithium cells may promise to be ideal as a rechargeable internal battery
      for a TAH, NiCd cells remain the most easily accessible off the shelf energy
      source. Twelve 1.2 A.hr prismatic NiCd (Sanyo, San Diego, CA) cells in series are
      being tested under the load condition of our TAH. The load consisted of a 1.5 A
      DC current with 1 A pulses of 40 msec duration at 3.33 Hz (100 bpm), a condition
      that can generate up to 8 L/min of cardiac output at physiologic pressures. Cells
      were tested at 37 degrees C. Cell voltages and temperatures were monitored.
      Testing was accelerated to five charge/discharge cycles per day. Discharge was
      terminated when any one cell dropped below 1.1 V. Charging (C/4) was continued
      until the battery voltage indicated a change in slope. Cell temperatures remained
      below 42 degrees C throughout the charge/discharge cycle. The battery pack
      settled to a nearly constant capacity of over 25 min after 10 cycles and has
      accumulated more than 1,000 cycles. Voltage differences among cells were small
      (SD < 25 mV), indicating consistency among cells. NiCd cells can serve as a
      reliable interim for TAH internal battery application.

PMID- 8268622
TI  - Quantitative bacterial analysis of porous, fabric, and smooth non-blood
      contacting implant surfaces and their tissue interfaces in a 169 day pneumatic
      total artificial heart animal recipient.
AB  - All long-term total artificial heart (TAH) survivals are subject to sepsis.
      Survival can be prolonged, but the source of the infection cannot be eliminated
      with any known course of antibiotics or treatment regimen. Sambo, a U-100 pTAH
      calf, survived 169 days. At week 6, he became septic, growing a Pseudomonas
      species (Ps). Weekly blood cultures were intermittently positive until week 13
      when they became continuously positive until his demise, from a ruptured left
      ventricular pumping diaphragm. Spatially specific porous silicone rubber (SSP)
      was used for surface modifications on the drive lines and as cuffs around the
      Dacron TAH graft to large vessel anastomoses. This gave an excellent opportunity
      to examine two types of porous implants surfaces (Dacron grafts and SSP) to the
      smooth Biomer ventricular surfaces with their respective adjoining tissue
      interfaces for bacterial colonization. Nine tissue samples and 13 implant
      surfaces were processed with Costerton's quantitative bacterial techniques. The
      largest numbers of bacteria (> 10(6)/cm2 Ps.) were grown from the smooth
      ventricular surface and in the cul-de-sac where the SSP delaminated from the
      driveline (two smooth implant surfaces in contact but without tissue apposition).
      The Dacron grafts were intermediate in bacterial concentrations and SSP surface
      modified drivelines and tissues were sterile. In this model, the more intimate
      biointegration found in the porous implants showed improved bacterial resistance
      in a chronically infected pTAH. The more completely biointegrated and neo
      vascularized porosity SSP was the only implant surface and opposing implant
      tissue interface sampled to remain sterile.

PMID- 8268623
TI  - Effect of sorbent-based dialytic therapy with the BioLogic-DT on an experimental
      model of hepatic failure.
AB  - An experimental model of hepatic failure in the dog has been developed in which
      the liver is devascularized in two stages. Under general anesthesia, a portacaval
      shunt is created, ligatures placed around the hepatic and gastroduodenal
      arteries, and the dog recovered. Two days later under general anesthesia, the
      ligatures are pulled, converting hepatic insufficiency to hepatic failure. Five
      control animals developed hypotension, severe lactic acidosis, hypoglycemia, and
      increasing liver enzyme levels during 6 hrs of follow-up. The BioLogic-DT system
      includes a cellulosic plate dialyzer with a suspension of powdered charcoal and
      cation exchangers as dialysate. Five animals were treated with the BioLogic-DT
      for 6 hrs after creation of hepatic failure. These animals were more stable
      physiologically, developed less lactic acidosis and less enzyme elevation, and
      maintained high normal blood glucose levels. The results help explain the
      clinical improvement demonstrated in patients with hepatic failure treated by the
      BioLogic-DT, and confirm that many of the toxins of hepatic failure are
      dialyzable and bound by simple sorbents such as charcoal and cation exchangers.

PMID- 8268624
TI  - Rescue from pediatric ECMO with prolonged hybrid intratracheal pulmonary
      ventilation. A technique for reducing dead space ventilation and preventing
      ventilator induced lung injury.
AB  - Hybrid intratracheal pulmonary ventilation (h-ITPV) is a continuous flow
      ventilatory technique that uses a "reverse thruster" catheter to redirect the
      flow of gas away from the carina. We report here the use of h-ITPV in a pediatric
      patient with acute sickle cell chest syndrome who required venoarterial ECMO
      support because of refractory hypoxemic respiratory failure. Her ECMO course was
      complicated by air leaks, coagulopathy, cardiac tamponade, and necrotizing
      tracheobronchitis. She could be weaned from ECMO only by maintaining high
      pressure conventional ventilatory support. To prevent ventilator induced
      barotrauma, we initiated h-ITPV and weaned her from ECMO bypass. After 12 days of
      h-ITPV, with tidal volumes of 2-3 ml/kg at carinal peak inspiratory pressures of
      25-30 cm H2O, the air leaks ceased and h-ITPV was discontinued. Dead space
      ventilation fraction (VD/VT) as low as 0.29 was achieved with this technique.
      Post-h-ITPV bronchoscopy displayed a dramatic resolution of the necrotizing
      tracheobronchitis. The patient survived and was discharged from the hospital. We
      conclude that the use of hybrid ITPV may facilitate weaning from ECMO to low
      pressure conventional ventilation and prevent the development of pulmonary
      barotrauma.

PMID- 8268625
TI  - Mechanical stress induced cellular orientation and phenotypic modulation of 3-D
      cultured smooth muscle cells.
AB  - The effect of periodic stretch on cellular orientation and intracellular
      ultrastructure of three-dimensionally (3-D) cultured arterial smooth muscle cells
      (SMCs) was investigated. Ring shaped hybrid tissues were prepared by thermal
      gelation of a mixed solution of Type I collagen and SMCs derived from bovine
      aorta. The gels were subjected to three modes of stress loading: floated
      (control), stretched isometrically (static stress), and periodically stretched
      and recoiled with 10% amplitude at 60 rpm frequency (dynamic stress). After 4
      weeks of stress loading, the gels were morphologically investigated with a light
      microscope and a transmission electron microscope (TEM). Irrespective of static
      or dynamic stress loading, SMCs in stress loaded gels exhibited an elongated
      bipolar spindle shape and were oriented parallel to the direction of stretch,
      whereas those in control gels were polygonal shaped and randomly oriented. TEM
      observation showed that SMCs in control and static stress loaded gels were
      intracellularly filled with organelles, such as rough endoplasmic reticulum, free
      ribosomes, Golgi complexes, and mitochondria, indicating that the cells were of
      the synthetic phenotype. On the other hand, SMCs in dynamic stress loaded gels
      tended to have increased contractile apparatus, such as myofilaments, dense
      bodies, and basement membranes, suggesting that periodic stretch plays an
      important role in phenotypic modulation of SMCs from the synthetic to the
      contractile state, as well as cellular orientation.

PMID- 8268626
TI  - A comparative study of complement activation by Denaflex, Bioflow, and
      BioPolyMeric vascular grafts.
AB  - This study was performed to evaluate the degree of complement activation by three
      bovine arterial graft materials: Bioflow (Bio-Vascular Inc., a bovine artery
      fixed with dialdehyde starch), BioPolyMeric (St. Jude Medical Inc., a collagen
      conduit of bovine arterial origin, tanned with glutaraldehyde and covered with a
      Dacron mesh), and Denaflex (Baxter Edwards CVS Division, a bovine artery fixed
      with polyepoxy compounds). The grafts were rinsed by following the manufacturer's
      recommended procedures and thereafter incubated with normal human serum. CH50
      assays were performed on the serum after incubation, and the percentage of
      complement activation for each sample was calculated relative to its control
      serum. The results indicated that the BioPolyMeric grafts activated the most
      complement, with about a 48% decrease in the CH50. The BioPolyMeric graft is
      composed of an outer polyester mesh and an inner collagenous tubing, exhibiting a
      nonreversible negative surface charge. After the polyester mesh was removed, the
      BioPolyMeric graft showed the highest complement activation in this study,
      suggesting that the glutaraldehyde fixed graft is more prone to complement
      activation than either the polyepoxy compound or dialdehyde starch fixed grafts.
      The complement fragment, C5a, generated during complement activation is strongly
      chemotactic for polymorphonuclear leukocytes and monocytes, which likely play
      early and long-lasting roles in regulating tissue reaction to the implanted
      graft.

PMID- 8268627
TI  - Portable data acquisition and control apparatus for implanted drug infusion pump
      interrogation.
AB  - Now that implantable drug infusion pumps are well established clinically, methods
      for diagnosing suspected pump failures are needed. The authors previously
      constructed a benchtop data acquisition and control apparatus to assist our work
      in developing new pump technology. Although this device is technically capable of
      in vivo pump monitoring, it is cumbersome. Thus, they recently created a portable
      interrogation unit with more limited features. This portable pump interrogation
      apparatus consists of a 32 bit MS-DOS labtop computer, data acquisition software,
      an analog/ASCII interface, a pressure transducer, and appropriate fluid conduits.
      Communication between the device and the implanted pump is via a percutaneous
      needle puncture of the drug reservoir refill septum. This procedure is identical
      to that employed in a standard pump refill. Pump performance is evaluated by
      incrementally filling the pump reservoir while simultaneously measuring reservoir
      pressure. The resulting data are presented on the computer screen as a plot of
      pressure versus volume that quickly and simply either eliminates or confirms the
      reservoir pressure source as a failure mode. Diagnostic runs are saved on file
      for archival purposes. Their benchtop apparatus has been a valuable and reliable
      tool over many years of use. The authors believe that their portable apparatus
      will be equally beneficial.

PMID- 8268628
TI  - A subcutaneous capillary filtrate collector for measurement of blood chemistries.
AB  - The capillary filtrate collector (CFC) contains 30,000 molecular weight cut-off,
      hollow fiber ultrafiltration membranes that are placed below the skin. A
      transcutaneous tube leads to an evacuated glass tube that provides a vacuum to
      pull ultrafiltrate at 40-60 microliters/hr from blood, through the fibers, and
      past a sampling port to the glass tube. Long-term (1-6 months) animal and
      clinical studies have shown that the ultrafiltrate concentration of chemicals
      such as glucose and a variety of drugs is exactly the same as that of the blood
      plasma water when the ultrafiltrate is created. In this study, the device was
      placed in six home monitored diabetics and four in-center hemodialysis diabetic
      patients. Over the following month, blood glucose concentrations were compared to
      CFC glucose concentrations. In spite of difficulties in diluting and assaying
      small samples of filtrate, there was a good correlation between blood and CFC
      glucose levels. A flow-through enzymatic glucose sensor has been tested and shown
      to accurately measure glucose in CFC filtrate. When placed in the transcutaneous
      tubing near the skin, this should allow a small external device to continuously
      monitor glucose levels in brittle or out of control diabetes with high accuracy
      and little risk, discomfort, or cost.

PMID- 8268629
TI  - Development of an autotuned transcutaneous energy transfer system.
AB  - A transcutaneous energy transfer (TET) system has been developed to power
      implanted devices such as heart assist devices, artificial hearts,
      defibrillators, and electrical stimulators. The TET system transfers power by
      electromagnetic induction without the need for percutaneous leads. For ease of
      implantation and patient comfort, it is desirable to use TET coils that are as
      small as possible. One problem encountered with TET designs that use small coils
      is a high sensitivity to coil electromagnetic coupling caused by changes in
      separation. These changes can result from variation in tissue thickness between
      subjects and from displacement of the coils that can occur during breathing and
      general body movement. Changes in coil coupling result in similar changes in the
      resonant frequency of the TET transformer, which can reduce power transfer and
      efficiency. The EVAD TET system was designed to address this problem by
      incorporating a technique for automatically tuning the power driver stage of the
      transformer. The system is able to deliver maximum output power of approximately
      60 watts at a coil separation of 5 mm, falling to approximately 45 watts at a
      coil separation of 15 mm. The system can deliver a maximum efficiency of 75-80%;
      reducing to approximately 60% and 60 watts. The results presented demonstrate the
      system's ability to compensate for variations in coil separation by resonant
      frequency tracking. This has optimized power transfer throughout the required
      range of coil coupling conditions.

PMID- 8268630
TI  - Sensing lead insulation fractures following implantable cardioverter
      defibrillator placement.
AB  - The insulation of implantable cardioverter-defibrillator (ICD) sensing leads can
      fracture, causing device malfunction. Before March 1989, 32 patients received
      silicon CPI K54 sensing leads. Of these, four (12.5%) experienced discharges
      while in sinus rhythm. Subsequent ICD interrogation revealed that abdominal
      muscular contraction triggered discharges in two patients, but no abnormal
      sensing could be elicited in the other two patients. These patients subsequently
      were found to have sensing lead fractures. All sensing leads appeared intact
      radiographically but at reoperation were found to have insulation fractures 2-4
      cm from the pin. The mechanism of fracture appears to be related to chronic
      intermittent lead compression between the anterior abdominal wall musculature and
      the ICD generator. Since March 1989, 134 patients have undergone ICD implantation
      with improved CPI 4312 sensing leads; none of these patients has experienced
      sensing lead fractures. The insulation of these leads is 2.5 times thicker than
      the K54 (1.0 mm vs. 0.4 mm). Patients with K54 sensing leads are at an increased
      risk for sensing lead insulation fracture and merit close surveillance. More
      importantly, sensing lead fractures must be considered in patients who present
      with inappropriate ICD discharges.

PMID- 8268631
TI  - Tissue distribution, circulating half-life, and excretion of intravenously
      administered protamine sulfate.
AB  - Intravenous protamine reversal of heparin anticoagulation may cause adverse
      hemodynamic side effects, but little is known about protamine's tissue
      distribution, circulating half-life (t/2), and excretion. The latter were
      assessed by examining 125I Bolton-Hunter (125I BH) radiolabeled protamine
      kinetics in a rat model. Three groups were studied: Group I controls (n = 5)
      received intravenous 125I BH label alone; Group II (n = 10) received intravenous
      125I BH radiolabeled protamine (0.15 mg/100 g); and Group III (n = 10) received
      intravenous heparin (15 IU/100 g) followed by intravenous 125I BH radiolabeled
      protamine (0.15 mg/100 g). Five animals in each group were killed at 3 min, and
      tissue radioactivity was quantitated. An additional five animals each in Groups
      II and III were followed up for 60 min to determine protamine's circulating t/2
      and its renal excretion. The lungs, heart, and kidneys, compared with other
      organs, retained the most 125I BH radiolabeled protamine per gram tissue at 3
      min. Retention of 125I BH radiolabeled protamine (Groups II & III) was greater (p
      < 0.05, Kruskal-Wallis) than control 125I BH label alone (Group I). Higher tissue
      125I activity was observed in Group II than in Group III rats, suggesting that
      tissue retention of protamine was greater in the absence of prior heparin
      administration. Circulating t/2 was shorter (18 vs. 24 min) and urinary protamine
      125I excretion was higher (34 vs. 24%) in Group III than in Group II,
      respectively, suggesting more rapid renal clearance of protamine in the presence
      of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268632
TI  - Significant enhancement of carbon dioxide removal by a new prototype IVOX.
AB  - The intravenacaval blood gas exchanger (IVOX) developed by Cardiopulmonics, Inc.
      has been tested in animals and in human clinical trials for partial support of
      gas exchange (25-30%) to allow reduction in mechanical ventilatory support and
      barotrauma during acute respiratory failure. After recognizing the limitations of
      the device and limited clinical utility of removing only 25-30% of CO2
      production, the authors have made design changes in the IVOX (prototypes IIA and
      IIB), including increased fiber number, decreased fiber length, decreased fiber
      diameter, and increased crimping. Nine ewes underwent placement of the IVOX
      prototypes in an ovine model of severe smoke inhalation injury. A modification of
      the original insertion technique was used to implant the prototypes. CO2 removal
      was directly measured from the outlet gas. O2 exchange was calculated from IVOX
      on/off measurements. Neither IVOX IIA nor IIB significantly changed hemodynamics
      when a fluid bolus (15 ml/kg) was infused before insertion. There were no
      significant differences between prototypes regarding thrombosis, emboli, or
      incidence of bleeding complications. Both prototypes significantly improved CO2
      removal (60-80%) compared with that reported for an older IVOX model. The
      improved gas transfer by these prototypes would serve to decrease mechanical
      ventilatory requirements and barotrauma in the treatment of severe respiratory
      failure.

PMID- 8268633
TI  - Development of an air lift pump oxygenator.
AB  - The authors devised an air lift pump oxygenator, comprised of double cylinders
      connected together and filled with perfluorocarbon (FC-75, 3M) as an oxygen
      carrier. While the oxygen enters the FC-75 through the lower inlet of one
      cylinder, the oxygenated FC-75 is lifted by an air lift pump and circulates in
      the two cylinders. FC-75 adds oxygen to the blood that infuses from the lower
      inlet of the other cylinder. The oxygenated blood is separated from the FC-75 by
      gravity and infused into the subject. The size of the cylinder is 2.2 cm in
      internal diameter and 17 cm in effective oxygenation height. The capacity of the
      oxygenator is 160 ml. PO2 went from 62 mmHg to 96 mmHg and PCO2 decreased from 31
      mmHg to 25 mmHg at a blood flow of 50 ml/min and an oxygen flow of 2 L/min.
      Maximum blood flow was 60 ml/min and the blood reserve capacity was 20 ml/min.
      The air lift pump oxygenator has advantages, such as simple structure, no motor,
      and a small priming volume.

PMID- 8268634
TI  - Multichannel stimulation of phrenic nerves by epineural electrodes. Clinical
      experience and future developments.
AB  - Between 1983 and 1992, 23 patients with complete ventilatory insufficiency of
      differing etiologies were treated with an eight channel implant (Medimplant Inc.,
      Vienna) for fatigue free stimulation of both phrenic nerves. Data for 15 patients
      with high spinal cord lesions (ages: 9-51 years) are summarized: 1) level of
      lesion: C0, 3 patients; C1/C2, 4; C2/C3, 8; 2) time between incident and
      implantation: 3-14 months; 3) diaphragm training: 1-22 months; 4) chronic pacing:
      5-83 months; 5) tracheostomy closed: 7 patients; 6) living permanently at home:
      13 patients; 7) respiratory rate per minute: 12-17; 8) duration of inspiration:
      1.0-1.3 sec; 9) tidal volume: 7-20 ml/kg body weight; 10) volume per minute: 121
      198 ml/kg body weight; 11) pH: 7.39-7.42; 12) pCO2: 22.9-38.6 mmHg; 13) pO2: 81.2
      104.5 mmHg; and 14) died by December 1992, 4 patients. All currently available
      implants for phrenic pacing need an external power supply and radio control. The
      authors have developed and tested the first fully implantable device. Features of
      this implant include an electronic circuit based on the microcontroller
      MC68HC705C8; surface mounted technology (SMD); eight channels; constant current
      source adjustable to 5 mA in 256 steps, impulse duration: 100-1000 musec,
      stimulation frequency: 1-33 Hz; and minimum lifetime: 3 years. The implant is
      programmed via bidirectional radio transmission using an IBM compatible computer.
      The dimensions, including battery, eight electrode connectors, and antenna, are
      67 x 48 x 13 mm. The implant weights 58 g. This new device may improve patients'
      safety and quality of life in the near future.

PMID- 8268635
TI  - Long-term follow-up of the experimental replacement of the esophagus with a
      collagen-silicone composite tube.
AB  - This study investigated ways of preventing late stenosis after replacing the
      esophagus with a prosthetic device and increasing survival time in an animal
      model. In a previous study, the authors induced neoesophageal formation and re
      epithelialization at an early stage, although stenosis in the chronic stage
      remained a problem, and long-term survival was prevented. The authors developed
      an artificial esophagus made from a collagen-silicone composite tube. The
      silicone tube (25 mm in diameter, 50 mm long, and 1 mm thick) was covered with
      collagen sponge (5 mm thick). The collagen sponge was intended to be replaced by
      host tissue, leading to neoesophageal regeneration. The authors thought stenosis
      was caused primarily by poor regeneration of submucosal tissue, rather than
      reepithelialization. Thus, they examined the grade of stenosis relative to the
      time the stent became dislodged. They concluded that the occurrence of stenosis
      after anastomosis depends upon the duration of stenting and that stenosis did not
      develop when the portion replaced by the artificial esophagus was stented for at
      least 4 weeks.

PMID- 8268636
TI  - Endothelial cell seeding onto the extracellular matrix of fibroblasts for the
      development of a small diameter polyurethane vessel.
AB  - A variety of experiments of endothelial cell seeding on artificial vessels have
      been performed. To improve endothelialization, one or two extracellular matrix
      components have been used as an underlying matrix. Although these methods have
      succeeded in in vitro experiments, they have not performed well in vivo. In this
      study, the authors used the whole extracellular matrix (ECM) excreted from
      fibroblasts as an underlying matrix. Fetal human fibroblasts were cultured on a
      polyurethane (PU) sheet. After confluence was attained, the cytoskeleton and the
      nuclei of the fibroblasts were destroyed using Triton-X, mitomycin, and
      irradiation. Omental microvascular endothelial cells from adult humans were
      seeded on various supports. After 12 days in culture, the cells were counted. The
      authors found that the ECM treated by irradiation had the highest cell number. In
      addition, the cells on this support exhibited the best morphologic appearance.
      Finally, the authors performed preliminary animal experiments. The PU vessels
      (inner diameter: 1.5 mm) treated with ECM were implanted in the arteries of rats.
      After the vessels had been implanted for 5 weeks, the authors found that the
      surface of the PU vessels were completely covered with endothelial cells. On the
      basis of these results, the authors conclude that the whole ECM makes a better
      underlying substrate for the endothelialization of small diameter artificial
      vessels.

PMID- 8268637
TI  - A functional neointima with regularly arranged smooth muscle cells in a fabric
      vascular prosthesis transplanted with autologous venous tissue fragments.
AB  - Regular arrangement of smooth muscle cells underneath an endothelial cell layer
      was observed in the neointima of a fabric vascular prosthesis treated with new
      technology to accelerate endothelialization, i.e., transplantation of autologous
      venous tissue fragments in the graft wall. This finding indicated that the
      neointima has a vital function as the intima of the blood vessel. A canine left
      jugular vein was minced and stirred into 20 ml of saline containing 1,000 IU
      heparin. It was injected with pressure into a fabric prosthesis (4 mm inner
      diameter [ID], 3.5 cm in length, Water porosity: 4,000 ml) to create the tissue
      fragmented, heparinized graft. The graft was implanted into the same animal from
      which the jugular vein was taken. Forty tissue fragmented heparinized (TFH)
      grafts were implanted in both carotid arteries of 20 dogs and explanted from 1 hr
      to 400 days after implantation. In this study, the neointimae of the grafts
      implanted for more than 1 month are analyzed, with a focus on the arrangement of
      smooth muscle cells in the neointima. A circumferential arrangement of smooth
      muscle cells with a thin layer of longitudinally arranged cells underneath was
      seen in the neointimae, which resemble the arrangement of smooth muscle cells in
      the natural arterial wall. Some areas had a thin smooth muscle cell layer in the
      longitudinal direction just under the endothelial cell layer. At anastomotic
      sites, they ran in parallel rows in the longitudinal direction. The authors
      previously clarified that the smooth muscle cells arrange in parallel rows in the
      direction of strain caused by tensile stress.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268638
TI  - Small diameter vascular prostheses with incorporated bioabsorbable matrices. A
      preliminary study.
AB  - The authors have designed small diameter vascular prostheses with incorporated
      matrices that can be absorbed into a growing anastomotic neointima. First, a
      gelatin-heparin complex was coated on the inner surface of tubular ultrafine
      polyester fabrics presealed with heat denatured albumin. Second, to control the
      bioabsorption rate, the prepared grafts were cross-linked with polyepoxy
      compounds for 3 days (Group I; n = 14) or 5 days (Group II; n = 4). These grafts,
      3 mm in diameter and 4 cm long, replaced the carotid arteries of nine mongrel
      dogs weighing 9.5-14 kg. Six of eight (75%) grafts in Group I were patent when
      the animals were killed 4 weeks after surgery. Doppler sound examination revealed
      that the remaining six were patent for 16 weeks. In Group II, three of four (75%)
      grafts were patent when the animals were killed 8 weeks after surgery. In both
      groups, scanning electron microscopic study showed neither platelet aggregation
      nor fibrin formation on the midportion. However, these two groups significantly
      differed in histology. In Group I, thin anastomotic neointima advanced over the
      mostly absorbed gelatin-heparin complex layer. Connective tissue was well formed
      around the polyester scaffold. In contrast, thick neointima advanced over the
      gelatin-heparin complex layer that still remained on the luminal surface in Group
      II. These results suggest that the gelatin-heparin complex, when cross-linked
      adequately, could simultaneously function as a temporary antithrombogenic surface
      and as an excellent substructure of an anastomotic neointima.

PMID- 8268639
TI  - Photo induced surface heparin immobilization.
AB  - This paper describes a novel method providing durable layering of heparin
      immobilized hydrogels on fabricated devices. The preparation method is based on
      photochemistry of a dithiocarbamate group that is dissociated into a highly
      reactive radical pair upon ultraviolet (UV) irradiation. By taking advantage of
      characteristics of the photo generated radicals, hydrogel formation and its
      fixation onto a substrate surface were attained. The immobilization of heparin
      onto poly(ethylene terephtalate) was demonstrated. First, a mixed aqueous
      solution containing a photoreactive water soluble poly(N,N-dimethylacrylamide
      covinylbenzyl N,N-diethyldithiocarbamate) and heparin was coated on the
      substrate. Subsequent UV irradiation resulted in the simultaneous formation of a
      heparin immobilized hydrogel and its chemical fixation onto the substrate. No
      delamination was found after vigorous washing with water. Significant inhibition
      of platelet adhesion and markedly prolonged blood coagulation times were
      observed, which are apparently derived from the surface hydrogel, and from
      released and chemically fixed surface heparin. Thus, it is expected that the
      photochemical method developed here provides potent antithrombogenicity to
      artificial organs.

PMID- 8268640
TI  - Development of an expandable intra-aortic prosthesis for experimental aortic
      dissection.
AB  - To achieve transcatheter entry obliteration for Stanford type B dissection, the
      authors devised and developed a self-expandable intra-aortic prosthesis (IA
      graft). This graft consisted of a microporous polyurethane graft (wall thickness:
      0.2 mm; average pore size: 0.1 mm) and an expandable metallic stent (Gianturco
      double stent) attached to the lumen surface of the polyurethane graft.
      Experimental dissections in the descending aorta of mongrel dogs were prepared.
      An IA graft was inserted through a femoral artery by a catheter sheath into which
      a compressed IA graft was installed and expanded at the entry site. After 30 min
      of graft implantation, closure of all the entry sites in four dogs was confirmed
      by aortography. The results suggest that the newly devised IA graft is extremely
      useful as a non invasive treatment for Stanford type B dissection.

PMID- 8268641
TI  - Modification of the frictional surfaces of artificial joints.
AB  - To overcome the wear problems associated with artificial joint materials, new
      surface structures with regular patterning were designed and fabricated. The
      lubrication properties were studied to evaluate the wear of the frictional
      surfaces. The surface structure was a pattern of "dents" with a diameter of 0.2
      1.0 mm and a pitch of 0.6-2.0 mm. The pattern was fabricated on the stainless
      steel (SUS) surface by a photochemical etching technique with 3 microns depth,
      and on an ultrahigh molecular weight polyethylene (UHMWPE) surface by mechanical
      processes. The time dependent changes of frictional force between SUS and UHMWPE
      were measured, and the surface morphologic changes were observed. The patterned
      surface showed lower frictional force than the smooth non-patterned surface, and
      less wear occurred on the patterned sample than on the sample without a pattern.
      There were optimum sizes for the diameter and the pitch of the pattern. These
      results demonstrated that lubrication properties could be improved by patterning
      of the frictional surfaces. The surface patterning was effective in preventing
      wear of the frictional surface, and the life of an artificial joint could be
      extended by such patterning.

PMID- 8268642
TI  - Production of platelet activating factor by human neutrophils after
      backfiltration of endotoxin contaminated dialysate.
AB  - Lipopolysaccharide (LPS) from gram negative bacteria has been shown to prime
      human polymorphonuclear neutrophil (PMN) production of platelet activating factor
      (PAF). PAF is a lipid mediator of inflammation and endotoxic shock and is also
      involved in leukocyte activation occurring during hemodialysis; PAF induces
      leukopenia, degranulation of lysosomal granules, and adherence to hemodialysis
      membranes. Transmembrane passage of LPS has also been shown to occur. To evaluate
      the relevance of transmembrane passage of LPS on the priming of PMN derived
      production of PAF, we designed in vitro studies using an experimental circuit
      equipped with different membranes (Cuprophan, polysulfone,
      polymethylmethacrylate, polyamide) and recirculation of purified human PMNs. At
      different time intervals, PMNs were stimulated with FMLP (10 microM) after back
      filtration of sterile and LPS contaminated dialysate. The results of these
      studies suggest that priming of PMN derived production of PAF was related to the
      percent of backfiltered LPS, and they emphasize the need for careful assessment
      of microbiologic quality to improve biocompatibility.

PMID- 8268643
TI  - A comparison of continuous arteriovenous hemofiltration and intermittent
      hemodialysis in acute renal failure patients in the intensive care unit.
AB  - Our experience with high flow CAVH (1-2 L/hr) and intermittent hemodialysis in
      our combined medical-surgical tertiary care intensive care unit was reviewed.
      During a 16 month period, 12 patients received CAVH and 23 patients received
      hemodialysis (3-7 days/week). Mean CAVH treatment duration was 5.5 days (0.5-18
      days). Hemodialysis patients received a mean of 4.3 treatments (1-16). CAVH
      patients had a mean age of 44.5 +/- 16.4 years (19-68), whereas the hemodialysis
      patients had a mean age of 60.9 +/- 14 years (34-82) (p = 0.004). Mean admission
      APACHE II score was 21.3 (11-29) for the CAVH group and 25.5 (10-39) for the
      hemodialysis group (p = NS). Peak ICU APACHE II score did not differ between
      groups (CAVH 26.2 [11-37], HD 28 [10-40]; p = NS). There were 4 deaths in the
      CAVH group (25%) and 19 deaths in the HD group (82%) (p = 0.006: chi-squared
      test). Although age was significantly different between groups, APACHE II scores
      were similar. Mortality rate was significantly higher in the hemodialysis group.
      This supports the hypothesis that CAVH may be the renal replacement therapy of
      choice in the ICU.

PMID- 8268644
TI  - Soluble tumor necrosis factor receptors are increased in hemodialysis patients.
AB  - Tumor necrosis factor-alpha (TNF alpha) interacts with cells through specific
      membrane receptors. Exposure to agonists, such as C5a, causes cells to shed these
      receptors, forming soluble TNF alpha binding proteins (sTNFR). Because cellulose
      membranes activate complement, we tested the hypothesis that dialysis with these
      membranes contributes to the increased levels of sTNFR observed in hemodialysis
      patients. sTNFR levels were measured pre- and post-dialysis in patients treated
      with dialyzers containing new cellulose membranes. Plasma sTNFR concentrations
      were markedly increased pre-dialysis, compared with normal (38.3 +/- 13.5 ng/ml
      versus 2.1 +/- 0.7 ng/ml), and increased further during dialysis, even after post
      dialysis concentrations were corrected for hemoconcentration. We examined the
      impact of the increased sTNFR levels on the ability of TNF alpha to prime
      neutrophil superoxide production in cross-incubation experiments. When normal
      neutrophils were incubated with TNF alpha in the presence of hemodialysis patient
      plasma, the resulting increase in fMLP stimulated superoxide production was
      significantly less than when normal plasma was used. Incubation of hemodialysis
      patient neutrophils in normal plasma only partly restored their ability to be
      primed by TNF alpha, suggesting an intrinsic functional defect in these cells, in
      addition to the effects of sTNFR. Our results suggest that dialysis with
      cellulose membranes contributes to the increased levels of sTNFR observed in
      dialysis patients, and that these concentrations are sufficient to impair the
      normal actions of TNF alpha.

PMID- 8268645
TI  - A new laparoscopic method for implantation of peritoneal catheters.
AB  - The placement of peritoneal catheters by non-surgeons was facilitated by a
      percutaneous laparoscopic technique ("Y-tec"). We have developed a catheter
      implantation system that is simpler to use, is less expensive initially and per
      procedure, and provides greatly enhanced peritoneal visualization. The core of
      the system is a 4 mm diameter Verres needle, which has a protective spring loaded
      obturator. This fits within a stainless steel cannula, which is in turn
      surrounded by a disposable peel away sheath. This entire unit is inserted into
      the peritoneal cavity through the rectus muscle after blunt dissection.
      Pneumoperitoneum is optional. The Verres needle is removed and peritoneoscopy is
      performed with a 5 mm Storz laparoscope. This is withdrawn, followed by the steel
      cannula, leaving the peel away sheath. The catheter is inserted through this,
      over a stylet. The sheath is then peeled off and the catheter sutured and
      tunneled in the usual fashion. This method uses the safest mode of blind
      peritoneal entry and permits thorough peritoneal inspection, even without
      insufflation. The needle and cannula are reusable, which minimizes cost. The
      technique is simple, and early results with inexperienced operators are
      encouraging.

PMID- 8268646
TI  - Experimental study of extracorporeal perfusion for septic shock.
AB  - The authors evaluated the efficacy of treatment by extracorporeal perfusion on
      experimental canine septic shock. Canine septic shock was produced by intravenous
      infusion of Escherichia coli endotoxin and treated by three techniques: no
      treatment (Sham), hemoperfusion over Polymyxin B immobilized fiber (PMX), and
      plasma perfusion over anion exchange resin (Resin). The 24 hr survival rates of
      the Sham, PMX, and Resin groups were 0%, 80%, and 40%, respectively. In the PMX
      group, blood pressure was significantly better over 6 hr than that recorded in
      the Sham group. In the PMX group, phagocytic function evaluated by neutrophil
      function, opsonic index, and complement were better than that of the Sham group.
      In addition, blood endotoxin levels in the PMX group were significantly lower,
      resulting in a significant suppression of TNF release. In the Resin group, some
      parameters were significantly better than those of the Sham group, but the
      efficacy of this treatment was less than that of the PMX treatment. Hemoperfusion
      over Polymyxin B immobilized fibers can detoxify circulatory endotoxin, resulting
      in improvement of systemic and organic disorders caused by sepsis.

PMID- 8268647
TI  - Continuous venovenous hemodiafiltration compared with conventional dialysis in
      critically ill patients with acute renal failure.
AB  - The morbidity and mortality benefits of new forms of continuous renal replacement
      therapy remain controversial. The authors have compared a cohort of consecutive
      prospectively studied critically ill patients with acute renal failure treated
      with continuous venovenous hemodiafiltration (CVVHD) (n = 76) to a previously
      described antecedent group of patients treated in intensive care with
      intermittent hemodialysis or peritoneal dialysis (conventional dialysis [CD]) (n
      = 84). Patients were comparable for mean age, gender distribution, and mean
      number of failing organs (CVVHD: 4; CD: 3.9). CVVHD patients were more severely
      ill as measured by APACHE II score (CVVHD: score of 29; CD: score of 25.8).
      Despite their greater illness severity, CVVHD patients more often survived to
      hospital discharge (CVVHD: 40.8%) than did CD patients (CD: 29.8%; NS). After
      adjustment for illness severity, in patients with two, three, or four failing
      organs, survival was 54.3% for CVVHD versus 29.3% for CD (p < 0.01). Survival was
      48% for CVVHD patients with an intermediate APACHE II score (24 to 29), compared
      with 12.5% for comparable CD patients (p < 0.01). No statistically significant
      differences were seen at either extreme of illness severity. Complications were
      significantly fewer during CVVHD (1 vs. 18). These data support the view that
      CVVHD reduces morbidity and mortality in critically ill patients with acute renal
      failure.

PMID- 8268648
TI  - The role of sequential ultrafiltration and varying dialysate sodium on vascular
      stability during hemodialysis.
AB  - Hypotension is a very common problem during HD. We studied vascular stability
      during sequential UF with constant and variable dialysate Na. Ten chronic
      patients underwent HD using two protocols. Protocol A was sequential UF (50%
      weight loss in the first hour, 30% in the second, and 20% in the third hour) with
      a dialysate Na of 140 mEq/L. Protocol B was sequential UF as in protocol A with
      varying dialysate Na (150 mEq/L in the first hr, 142 in the second, and 137 in
      the third). BP and pulse were monitored every 30 min. Hct, BUN, creatinine,
      osmolality, and serum albumin were checked every hour. The plasma volume
      decreased by 5.3% in protocol A as compared with 1.2% in protocol B, as shown by
      the Hct values. The decrease in serum osmolality during the first and second
      hours was more marked in protocol A than in protocol B (p < 0.05), but post
      dialysis values were similar. The clinical parameters (UF, BP, pulse rate) and
      serum Na showed no difference. The intradialytic mannitol infusion was 10 ml/HD
      and 0, whereas saline was 80 ml/HD and 10 for A and B, respectively. These data
      suggest: (1) Sequential UF with varying dialysate Na could benefit patients who
      are hemodynamically unstable. (2) The need for mannitol and saline may be more
      readily alleviated with protocol B than with protocol A. (3) The beneficial
      effect of varying dialysate Na with sequential UF may be due to improved plasma
      refilling and decreased early intradialytic osmolar changes.

PMID- 8268649
TI  - Deficiency of serum ionized magnesium in patients receiving hemodialysis or
      peritoneal dialysis.
AB  - Serum total magnesium (TMg) measurements in dialysis patients are variable, with
      some groups reporting hypermagnesemia and some hypomagnesemia. It had not been
      possible to measure the biologically active fraction, ionized magnesium (IMg2+).
      The authors utilized an ion-selective electrode to measure IMg in 26 hemodialysis
      patients and 10 peritoneal dialysis (CAPD) patients and compared the results with
      those from 66 age matched control subjects. Dialysate magnesium was 0.375 mM/L
      for the hemodialysis and 0.25 mM/L for the CAPD patients. When compared with
      control subjects, both hemodialysis and CAPD patients had significantly lower
      IMg2+ (0.55 +/- 0.02 and 0.50 +/- 0.02 vs. 0.60 +/- 0.004 mM/L; p < 0.05) and
      greater or normal TMg values (0.99 +/- 0.04, different at the p < 0.001 level,
      and 0.85 +/- 0.04 vs. 0.84 +/- 0.008). Ionized calcium (ICa2+) values were
      similar for all three groups (1.15 +/- 0.02 and 1.21 +/- 0.04 vs. 1.17 +/- 0.01),
      resulting in increased mean ICa2+/IMg2+ ratios (2.14 +/- 0.07 and 2.42 +/- 0.06
      vs. 1.95 +/- 0.02 for the control subjects; p < 0.05). The percent of total
      magnesium that was ionized (%IMg2+) was low in both the hemodialysis and CAPD
      patients (55.6 +/- 0.93 and 59.2 +/- 1.05) compared with that of control subjects
      (72 +/- 0.61; p < 0.05). IMg2+ values correlated with TMg values in both
      hemodialysis (r = 0.93; p < 0.0001) and CAPD (r = 0.92; p < 0.0001) patients did
      not correlate with age, time on dialysis, weight, fasting cholesterol or
      triglyceride, albumin, blood urea nitrogen (BUN), creatinine, hematocrit,
      phosphate, or PTH values.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268650
TI  - Acute dialytic support of the octogenarian: is it worth it?
AB  - Dialytic support of the elderly has recently come under scrutiny. The consumption
      of resources and the lack of clear data on outcome have fueled the controversy.
      In an effort to establish a baseline, we reviewed our experience over the past 5
      years of ICU dialysis therapies delivered to patients over 80 years old. Data
      were prospectively collected for an ICU Renal Registry and included admission
      diagnosis, presence of pre existing renal dysfunction (serum creatinine > or =
      1.5 mg/dl), APACHE score at both ICU entry (A1) and consultation (A2), presence
      of multiorgan failure (MOF), pressor support (PS), nutritional support (NS),
      therapy type used (both prescribed and delivered), and outcome, either as ICU
      discharge, return of renal function, or withdrawal. A total of 21 patients
      (average age 82.6; range, 80-88 years) consisting of 4-8% of the yearly
      consultations underwent renal replacement therapy. The majority of patients were
      surgical (20/21); 61.9% had pre-existing renal dysfunction (serum creatinine 2.1
      +/- 1.4 mg/dl) and presented with ARF from ischemic/toxic causes (17/21) or other
      causes (4/21). Virtually all patients had MOF (20/21) with moderately elevated
      APACHE scores (A1: 20.9, A2: 21.3). Eighty-six percent received PS, and 90%
      received NS. Renal therapy consisted of only intermittent (9/21), only continuous
      (4/21), or a combination (8/21). These data were compared with those of 80+ year
      old patients who underwent surgery but did not require dialysis, as well as with
      those of non 80 year old dialysis supported ICU patients over the same 5 year
      period. Patient outcome reflected a 33.3% overall survival and a 28.5% renal
      recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268651
TI  - Characterizations of candidate genes for IDD susceptibility from the diabetes
      prone NOD mouse strain.
AB  - The nucleotide sequences of the NOD and C57BL/6J alleles of Glut-2, Sod-2, and Il
      2 were determined by RT-PCR sequencing. Each of these loci is located in
      intervals that strongly correlated with susceptibility to diabetes in an (NOD/Uf
      x C57BL/6J)F1 x NOD/Uf backcross. No significant variations in the alleles of
      Glut-2 at 16 cM on Chromosome (Chr) 3 or Sod-2 at 8 cM on Chr 17 were detected.
      However, the Il-2 allele in NOD at 20 cM on Chr 3 was found to differ from that
      in C57BL/6J by a complex mutation involving the contraction of a simple sequence
      repeat (SSR). Il-2 in NOD differs from the allele in C57BL/6J via a complex
      mutation involving a deletion of four CAG codons from the SSR together with a
      length-compensatory four-codon duplication of a segment 5' from the SSR. Two
      nonsynonymous mutations in the coding region 5' to the SSR were also detected.
      Only these two allelic forms of Il-2 were detected in a survey of 13 standard
      inbred lines and 4 wild mouse strains. We propose to designate these alleles as
      Il-2a (for alleles such as C57BL/6J that contain 12 CAG repeats) and Il-2b (for
      alleles such as NOD), which occurred in a variety of standard inbred strains and
      in all four wild Mus musculus domesticus tested. The distribution of these Il-2
      alleles among inbred strains correlated with the detection of Chr 3 as an
      interval effecting diabetes susceptibility in three separate genetic
      crosses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268653
TI  - The genetic map around the tail kinks (tk) locus on mouse chromosome 9.
AB  - Tail kinks (tk) is a classical mouse skeletal mutation, located on Chromosome
      (Chr) 9. As the first step for the positional cloning of the tk gene, we have
      established a genetic map of a region surrounding the tk locus by generating a
      backcross segregating for tk. From this backcross, 1004 progeny were analyzed for
      the coat-color phenotype of the proximally located dilute (d) gene and for the
      distally flanking microsatellite marker, D9Mit12. Fifty-six recombinants between
      d and tk and 75 recombinants between tk and D9Mit12 were identified, completing a
      panel of 130 recombinants including one double recombinant. This panel allowed us
      to map five microsatellite loci as well as d and Mod-1 with respect to tk. We
      show that one of the microsatellite markers mapped, D9Mit9, does not recombine at
      all with tk in our backcross. This indicates that the D9Mit9 locus will serve as
      a good starting point for a chromosomal walk to the tk gene.

PMID- 8268652
TI  - The little (lit) mutation cosegregates with the growth hormone releasing factor
      receptor on mouse chromosome 6.
AB  - The little (lit) autosomal recessive mutation in the mouse causes dwarfism due to
      isolated growth hormone deficiency. The in vitro physiology of pituitary growth
      hormone release in lit/lit animals suggests that an abnormality in the growth
      hormone releasing factor (GRF) receptor (Ghrfr) is a very likely candidate for
      the lit mutation. We mapped Ghrfr to the region around lit on Chromosome (Chr) 6
      in 100 chromosomes of an FVB x Czech II interspecific backcross. Molecular
      markers were Neuropeptide Y (Npy), homeobox (Hoxa2), immunoglobulin kappa chain
      (Igk), wingless-related MMTV integration site (Wnt-2), cystic fibrosis (Cftr),
      carboxypeptidase A (Cpa), and Ghrfr. Map order and distances were as follows: Cen
      II-Wnt-2-(0 cM)-Cftr-(6.0 cM)-Cpa-(8.0 cM)-Npy-(1.0 cM)-Hoxa2-(3.0 cM)-Ghrfr-(2.0
      cM)-Igk. We mapped lit (by phenotype) relative to Hoxa2 and Igk on 72 F2
      chromosomes of offspring of a B6CZ lit/ + x B6FVB lit/ + intercross and 18
      chromosomes of offspring of a B6FVB lit/ + intercross. Map order and distances
      were as follows: Hoxa2-(2.1 cM)-lit/Ghrfr-(3.7 cM)-Igk. No recombinations between
      lit and Ghrfr were detected. Thus, Ghrfr maps to mouse Chr 6 and may be allelic
      with lit. Amplification of a short segment at the 3' end of the Ghrfr mRNA by
      reverse transcription coupled to the polymerase chain reaction showed a greatly
      diminished level of GRF receptor mRNA in the pituitaries of lit/lit mice as
      compared with lit/ + controls. Low level of message could reflect a primary
      molecular defect or be due to secondary hypoplasia of somatotropes.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8268654
TI  - Recruitment of multiple alleles within the Eb recombinational hotspot in murine
      MHC.
AB  - Genetic recombination has been proposed to have played a major role in generating
      the extensive polymorphism that distinguishes the genes of the major
      histocompatibility complex (MHC). The proximal region of the murine H-2
      represents a unique segment of DNA encompassing at least four hotspots for
      meiotic recombination. One of these hotspots lies within the second intron of the
      class II Eb gene and has been defined at the nucleotide level for a number of
      simple two-allele crosses. In this report we studied two crosses in which one or
      both parents in themselves were H2Eb recombinants and three alleles were present
      within the hotspots of each pair of the parental haplotypes. Nucleotide analysis
      indicated that the break points in these secondary recombinants, like those in
      the primary recombinants, were also discrete and clustered within the H2Eb second
      intron. Thus, in one instance two and in the other instance three alleles were
      present within the hotspots of these recombinants. These observations strongly
      suggest that meiotic recombination could be an important mechanism contributing
      to MHC polymorphism.

PMID- 8268655
TI  - DNA segments mapped by reciprocal use of microsatellite primers between mouse and
      rat.
AB  - Rat microsatellite primers were used for detection of homologous DNA segments in
      the mouse species (Mus laboratorius, Mus musculus musculus, and Mus spretus).
      Twenty five (16.3%) of 153 rat primer pairs amplified specific DNA segments, when
      genomic DNA of mice was used as a template in the polymerase chain reaction
      (PCR). Size variation among inbred strains of mice was found for 13 DNA segments
      (8.5%). Eight out of the 13 polymorphic DNA segments were mapped to a particular
      chromosome with two sets of recombinant inbred strains, AKXL or BXD. Similarly,
      mouse microsatellite primers were used for detection of homologous DNA segments
      in rats (Rattus norvegicus). Twenty (12.0%) of 166 primer pairs amplified
      specific DNA segments from rat genome. Size variation among inbred strains of
      rats was found for seven DNA segments (4.2%). Eleven of these 20 DNA segments
      were mapped with a rat x mouse somatic cell hybrid clone panel and/or linkage
      analysis by use of backcross progeny. Our results suggest that the mapped DNA
      segments are really homologs between mouse and rat. These polymorphic DNA
      segments are useful genetic markers.

PMID- 8268656
TI  - Characterization and mapping of the human SOX4 gene.
AB  - The SOX genes comprise a large family related by homology to the HMG-box region
      of the testis-determining gene SRY. We have cloned and sequenced the human SOX4
      gene. The open reading frame encodes a 474 amino acid protein, which includes an
      HMG-box. The non-box sequence is particularly rich in serine residues and has
      several polyglycine and polyalanine stretches. With somatic cell hybrids, human
      SOX4 has been mapped to Chromosome (Chr) 6p distal to the MHC region. There is no
      evidence for clustering of other members of the SOX1, -2, and -3 or SOX4 gene
      families around the SOX4 locus.

PMID- 8268657
TI  - Assignment of 22 loci in the rat by somatic hybrid and linkage analysis.
AB  - Twenty structural genes and two unique anonymous DNA fragments have been mapped
      in the rat (Rattus norvegicus) with a panel of mouse x rat hybrids and linkage
      analysis. Ten of the 20 autosomes are represented by at least one of these
      markers. A new syntenic relationship among rat Chromosome (Chr) 16, mouse Chr 14,
      and human Chr 10q was established. Results of this study further support the
      extensive conservation of synteny between the rat and mouse and, to a lesser
      degree, between rat and human.

PMID- 8268658
TI  - Characterization of a porcine glucosephosphate isomerase-processed pseudogene at
      chromosome 1q1.6-1.7.
AB  - A porcine glucosephosphate isomerase-processed pseudogene has been isolated and
      sequenced. The pseudogene has several base substitutions as well as an insertion
      and deletions, and is 83% homologous to the corresponding cDNA. It contains an
      intervening sequence of 565 bp, is truncated at the 3' end, and is flanked by
      direct repeats of seven nucleotides. Fluorescent in situ hybridization to porcine
      metaphase chromosomes localized the processed pseudogene to Chromosome (Chr)
      1q1.6-1.7. A (GT)14(AT)15 microsatellite was detected close to the processed
      pseudogene.

PMID- 8268659
TI  - Comparative gene mapping of lactoperoxidase, retinoblastoma, and alpha
      lactalbumin genes in cattle, sheep, and goats.
AB  - The lactoperoxidase (LPO), retinoblastoma (RB1), and alpha-lactalbumin (LALBA)
      genes have been mapped by fluorescent in situ hybridization respectively to
      cattle Chromosomes (Chrs) 19, 12, 5; goat Chrs 19, 12, 5; and sheep Chrs 11, 10,
      3. The results confirm the homologies among cattle, sheep, and goat chromosomes,
      previously reported, and provide more information for the comparison between the
      bovine and human karyotypes and gene maps.

PMID- 8268660
TI  - Isolation and characterization of a genomic clone from the murine utrophin locus.

PMID- 8268661
TI  - Localization of the murine Hmg1 gene, encoding an HMG-box protein, to mouse
      chromosome 2.
AB  - In conclusion, using concatenated AhRE sequences and the recognition site probe
      methodology, we have cloned the murine Hmg1 cDNA and determined an additional 141
      bp of 5' noncoding sequence (GenBank Accession No. S50213; entry name MUSHMG1A).
      The gene product represents an HMG-box transcription factor that recognizes DNA
      shape- and sequence-specific elements; this is perhaps the reason that this cDNA
      was isolated with concatomeric oligonucleotides. We have mapped the Hmg1 gene to
      mouse Chr 2, between regions homologous with human Chr 2q and 11p11-q12.

PMID- 8268662
TI  - Corticotropin-releasing hormone (Crh) maps to mouse chromosome 3.

PMID- 8268663
TI  - Mapping of the neural retina leucine zipper gene, Nrl, to mouse chromosome 14.

PMID- 8268664
TI  - LINE-1 element in the vole Microtus subarvalis.

PMID- 8268665
TI  - Encyclopedia of the mouse genome III. October 1993.

PMID- 8268666
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 1.

PMID- 8268668
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 8.

PMID- 8268667
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 7.

PMID- 8268669
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 9.

PMID- 8268670
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 10.

PMID- 8268671
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 11.

PMID- 8268672
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 12.

PMID- 8268673
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 13.

PMID- 8268674
TI  - Encyclopedia of the mouse genome III. October 1993. Master locus list.

PMID- 8268675
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 14.

PMID- 8268676
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 15.

PMID- 8268677
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 16.

PMID- 8268678
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 17.

PMID- 8268679
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 18.

PMID- 8268680
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 19.

PMID- 8268681
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse X chromosome.

PMID- 8268682
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse Y chromosome.

PMID- 8268683
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 2.

PMID- 8268684
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 3.

PMID- 8268685
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 4.

PMID- 8268686
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 5.

PMID- 8268687
TI  - Encyclopedia of the mouse genome III. October 1993. Mouse chromosome 6.

PMID- 8268688
TI  - How do we bring new technology into optometry?

PMID- 8268689
TI  - Injury to the cornea.
AB  - Ocular trauma represents one of the most frequent and challenging clinical
      presentations confronting the primary eye care provider. The degree of damage to
      the ocular tissues can range from mild to severe. It is imperative that the
      managing practitioner be able to rapidly assess the level of injury and take
      appropriate steps to minimize ocular morbidity, thereby maximizing the return of
      normal visual function. Corneal injuries can be divided into three major
      categories: mechanical, chemical, and radiant energy. This discussion will deal
      with the general management of mechanical types of injuries.

PMID- 8268690
TI  - Legal aspects of management of ocular trauma.
AB  - Patients suffering from blunt ocular trauma pose several legal challenges for
      primary eye care practitioners. Although optometrists in private practice are
      under no legal duty to examine patients with ocular trauma, failure to do so
      breaches ethical considerations. When an optometrist undertakes examination of an
      injured patient, a medical standard of care will be applied, and "Good Samaritan"
      statutes afford no shield from liability for negligence committed during the
      course of examination and treatment. If specialized care is necessary, a timely
      referral must be arranged. Practitioners are liable for the acts or omissions of
      employees, and receptionists who schedule appointments should be able to triage
      patient complaints so that same-day appointments are scheduled for patients
      requiring urgent assessment and care. Documentation of the disposition of these
      patients is essential; forms are an ideal way to record and preserve essential
      information.

PMID- 8268691
TI  - The initial assessment of ocular contusion injury.
AB  - The initial assessment of blunt ocular trauma requires taking a thorough history,
      measuring visual acuity, evaluating pupils, extraocular muscles, intraocular
      pressure, and anterior adnexa, and examining the interior of the eye by means of
      biomicroscopy and ophthalmoscopy. More sophisticated means of examination may be
      necessary before treatment strategies can be determined. The most common types of
      injuries are contusions, abrasions, lacerations, and penetrating wounds of the
      eye. The most serious injuries requiring treatment are penetrating wounds,
      hyphemas, and retinal detachments. The initial goal of management is to provide
      timely recognition and treatment of the injury, and to stabilize the condition
      and promptly refer the patient if specialized care is necessary.

PMID- 8268692
TI  - Management of ocular emergencies.

PMID- 8268693
TI  - Traumatic anterior uveitis.
AB  - Traumatic anterior uveitis is a common result of ocular contusion. Patients
      require careful evaluation to determine the degree of injury and the risk of
      further complications. This discussion updates the practitioner on the
      pathophysiology, diagnosis, and treatment of anterior uveitis secondary to a
      nonpenetrating ocular injury.

PMID- 8268694
TI  - Hyphema.
AB  - Hyphema is a potentially sight-threatening sequela of blunt trauma. Delayed
      healing time, poor visual outcome, and complications such as corneal blood
      staining, anterior and posterior synechiae, increased intraocular pressure, and
      glaucomatous optic atrophy are most often associated with hemorrhage filling more
      than one half of the anterior chamber. Rebleeds are most likely 3 to 5 days
      following injury, in children, in blacks (particularly if they have sickle cell
      disease), and in persons who have ingested aspirin or other antiplatelet
      compounds. Treatment of hyphema is controversial, and medical therapy
      (antibiotics, cycloplegics, steroids, aminocaproic acid) should be tailored to
      suit the needs of each case. Intraocular pressure-reducing medications may be
      required if there is significant elevation of IOP. The affected eye should be
      protected with a shield, and follow-up examinations should be conducted as
      necessary. Both the anterior and posterior eye should receive careful assessment.

PMID- 8268695
TI  - Angle recession.
AB  - Angle recession is a relatively common result of ocular injury, which, if
      extensive, creates a noteworthy risk of elevated intraocular pressure (IOP) and
      glaucoma. The unilateral elevation in IOP is usually seen long after the injury
      has occurred. The diagnosis is often made based on clinical suspicion, either
      because of information obtained during the history-taking or from signs of ocular
      trauma observed during the examination. The treatment of angle-recession glaucoma
      is in many ways similar to that of primary open-angle glaucoma, although miotic
      drugs and argon laser trabeculoplasty are controversial therapies for this
      condition.

PMID- 8268696
TI  - Traumatic cataract.
AB  - Cataract formation is commonly observed as a result of direct penetration of the
      crystalline lens by a foreign object or by blunt trauma to the globe or adnexa,
      creating a "shock wave" within the eye. Partial or total damage to the zonules
      may also occur, resulting in subluxation or total displacement of the crystalline
      lens. The primary care doctor of optometry plays an important role in evaluating
      patients with cataract, both immediately and long after the injury has occurred.
      Many of these patients can be managed conservatively by careful observation,
      while others will require surgical intervention.

PMID- 8268697
TI  - Orbital fractures.
AB  - The optometrist is often the first practitioner to see patients with ocular
      trauma and associated orbital fractures. Trauma is now the second leading cause
      of blindness in the United States. Early and accurate diagnosis of orbital
      fractures is required to avoid compromising the binocular vision and cosmetic
      appearance of the patient. With an understanding of the characteristic clinical
      presentations of fractures and a knowledge of current imaging techniques, these
      disorders can be accurately diagnosed, managed, or referred by the optometrist.

PMID- 8268698
TI  - Traumatic retinal detachment.
AB  - Ocular contusion may result in numerous types of retinal breaks, including
      horseshoe tears, operculated holes, large irregular retinal breaks, macular
      holes, and, most often, retinal dialyses. Supranasal dialyses have a high
      correlation with trauma and may require months before symptoms appear. Large
      irregular breaks occur only following trauma and may be found in the area of
      contusion. Horseshoe-shaped tears and operculated holes may occur at areas of
      vitreoretinal attachment. Macular holes may also occur from trauma, either from
      detachment of vitreous or as a sequela of retinal edema. Careful examination of
      the posterior pole and retinal periphery is necessary when there is a history of
      trauma or findings indicative of a past episode of trauma. Binocular assessment
      of the retina is a prerequisite to conducting an appropriate examination.

PMID- 8268699
TI  - Optic nerve trauma.
AB  - Trauma to the optic nerve may be direct, such as from a penetrating object, or
      indirect, which may result despite lack of direct contact of an object with the
      nerve. Although indirect injury initially causes no change in the appearance of
      the nerve head, within a matter of weeks optic atrophy will be manifest. The
      pathophysiology of nerve damage is incompletely understood. Management is
      controversial; steroid therapy has been advocated, as has surgical decompression
      of the nerve. Indirect injuries affecting the optic nerve may also result from
      torsional rotation of the globe (avulsion) and from subdural or subarachnoid
      hemorrhage (Terson's syndrome). There is no treatment for optic nerve avulsion;
      the unaffected eye should be protected with appropriate eyewear. Hemorrhaging in
      the retina and vitreous in Terson's syndrome should be monitored for resolution
      and risk of retinal detachment. Computed tomography may be necessary if
      subarachnoid or intracranial hemorrhages are suspected.

PMID- 8268701
TI  - [Use of the MDK in implementing the psychiatric personnel regulation (Psych-PV)-
      report of experiences].

PMID- 8268700
TI  - [Regional distribution and temporal development of infant mortality in West
      Germany 1973-1988].
AB  - Infant mortality was documented for the Federal Republic of Germany as well as
      for the individual Federal Laender (before German unification) during 1973 and
      1988. 31 Cause-of-Death groups, 5 Age-of-Death groups, and both sexes were
      considered. During the observation period the infant mortality rate decreased to
      1/3 of the value of 1973 and is now well below 1%. The temporal decrease of
      infant mortality is different with regard to causes of death, age of death, sex,
      and Federal Land: Infant mortality due to congenital malformations decreased to
      about one half within the observation period, but its relative contribution to
      all natural causes of death increased from about 20% in 1973 to about 30% in
      1988.

PMID- 8268702
TI  - [Work disability in long-term illness--Part 2: Termination of employment].
AB  - If the employment has terminated and the performance capacity of the employee is
      no longer up to demands made by his last job, the second consideration in respect
      of his disablement concerns the following points: similar work to be performed
      within the narrow framework of his former in case of compensation payment because
      of unemployment: activities within the framework of jobs he can be judged to
      perform, as laid down by German labour legislation in respect of compensation
      payments to the unemployed. The compulsory sickness body will have to clarify by
      expertising which activities can be considered as yardsticks from a medical point
      of view.

PMID- 8268703
TI  - [Blood donors as the sentinel population for sexually transmissible diseases-
      results of a sociodemographic study and survey of sexual behavior].
AB  - A multipurpose survey in a representative sample of the german population was
      conducted to obtain sociodemographic data together with data on blood donation
      history and acceptance of HIV antibody tests. A self-administered questionnaire
      was used to gather information on sexual behaviour. This questionnaire was
      completed by 62.2% of the participants between 18 and 64 years of age. Comparison
      between donors and nondonors shows that donors are typically members of the more
      "socially active" groups: they are younger, gainfully employed, and have attained
      higher educational levels. The analysis of the data on sexual behaviour reveals
      that donors are on the average sexually more active than nondonors. Blood donors
      are a suitable sentinel population to monitor sexually transmitted diseases in
      the population outside the risk groups for HIV infection.

PMID- 8268704
TI  - [Lead in drinking water--determination of a new limit value and the problem of
      lead pipes].
AB  - The problem of lead in drinking water with regard to sensitive groups of the
      general population (e.g. unborn, babies that are not breast-fed, infants and
      children) is discussed. In respect of children in nurseries, the question
      regarding the relation of blood-lead levels to neurobehavioural deficits due to
      lead as well as a theoretical "tolerable" daily intake of lead is discussed. A
      provisional daily intake of approx. 1.2-1.3 micrograms Pb/kg body weight for
      children and pregnant women is proposed. For non-pregnant adults a double to
      three times higher intake may be tolerated (base: high blood pressure). These
      doses are well three times below the still recognised Provisional Tolerable
      Weekly Intake of led (PTWI-values, WHO), when related to daily intake.
      Considering the water consumption as well as the proportionate share of other
      exposure routes which result in the total lead exposure of risk groups, a
      toxicologically tolerable level of 10 micrograms Pb/l in drinking water is
      suggested. A reduction of the actual limiting value in drinking water (40
      micrograms Pb/l) is advised. A special problem arises from lead tubes within the
      water distribution system. Water in stagnation as well as in use in these tubes
      may have enhanced lead concentrations. Therefore, it is recommended to exchange
      lead tubes preferentially in areas of sensitive use (e.g. as in the kitchen).

PMID- 8268705
TI  - [Handling of red silica gravel on sports, play and resort surfaces with special
      reference to new toxicologic results].
AB  - In 1991 "Kieselrot", a material with extremely high PCDD/PCDF-contamination up to
      about 200,000 ng TEQ/kg was detected on many leisure centres and sports fields in
      Germany. The contaminated grounds were closed, and covered up. The following
      examinations to prepare the planned decontamination are described here. The need
      for decontamination of those "Kieselrot"-areas is discussed with special
      reference to its relevance on behalf of environmental toxicology and preventive
      medicine. Risk estimates, based on mathematical models had shown a considerable
      health and cancer risk for the users of such play- and sports grounds. However,
      recent studies conducted with sportsmen, groundsmen, and residents after many
      years of contact with "Kieselrot"-covered grounds did not reveal any additional
      PCDD/PCDF blood fat burden. But raised TEQ-levels and a typical congeneric
      pattern pointing to a "Kieselrot"-load could be seen in some of the examined
      children. Following these results it was concluded that children play grounds
      contaminated with "Kieselrot" should remain closed and should be decontaminated,
      whereas sports fields could be used again. Another possibility could be the
      adaption of the decontamination concepts and methods to the proven low
      bioavailability of PCDD/PCDF from "Kieselrot".

PMID- 8268706
TI  - [Nitro-musk compounds in breast milk].
AB  - Musk xylene, ketone, ambrette, tibetene and moskene are synthetic nitroaromatic
      compounds. Because of their scent, they are used as substitutes for natural musk.
      In particular musk xylene and musk ketone are added to cosmetics, washing agents
      and other products. Acute toxicity of nitro musks has been estimated to be low.
      Knowledge on the toxicokinetics, chronic toxicity, as well as mutagenic and
      carcinogenic potential is based so far on only few studies. First evidence for
      the persistence of these lipophilic compounds in the environment and their
      potential to accumulate in organisms came from their identification in the
      aquatic ecosystem. Nitro musks have now been identified in mother's milk. The
      analysis of 391 samples from Southern Bavaria, Germany, in 1991 and 1992 revealed
      concentrations of musk xylene ranging from 0.01-1.22 mg/kg fat with a mean
      content of 0.10 mg/kg fat. This was 2-3 times higher than the mean contents of
      musk ketone or musk ambrette. Average levels of the nitro musks were in the range
      of those usually found for various chlorinated compounds like
      hexachlorocyclohexanes and cis-heptachloroepoxide. Because of their presence in
      cosmetic products and washing agents dermal absorption could be an important
      route of uptake of nitro musks in man. Toxicologic relevance of the present
      findings for humans is still unclear. In order to assess consequences for health,
      further investigation of effects caused by a continual uptake of small amounts of
      these substances is necessary.

PMID- 8268707
TI  - [Thoughts on the problem of expert assessment of severe disability in very young
      children].
AB  - Opinions on the necessity of nursing severely disabled infants (section 53 SGB V)
      are very often difficult for experts of sickness insurances, because even healthy
      infants in their first years require a much assistance and must be permanently
      looked after. By evaluating 17 such cases an attempt is made to find aspects of
      retardation of development and possibly simultaneously existing mental handicaps
      and moreover factors to substantiate a considerably greater need for help
      compared to normal infants of the same age.

PMID- 8268708
TI  - [Comment on the contribution by H. Burow: "Increase in infections caused by
      Salmonella enteritidis--causes and possibilities for intervention"].

PMID- 8268709
TI  - Properties and regulation of human platelet cation channels.
AB  - The stimulation of calcium influx by various human platelet agonists which differ
      in their activation pathways was investigated. ADP activates a receptor-operated
      cation channel (ROC) and stimulates a phospholipase C (PLC)/inositol
      trisphosphate (IP3)-mediated calcium mobilization associated with a secondary
      calcium influx. Thrombin only stimulates the PLC/IP3-mediated calcium
      mobilization and associated calcium influx, perhaps followed by an additional
      phase of calcium influx. The platelet calcium response after incubation with the
      thromboxane A2 mimetic U 46619 is similar but more transient compared to that
      after thrombin stimulation. Tert-butylhydroquinone (an inhibitor of endoplasmatic
      reticulum Ca(2+)-ATPases and cyclooxygenase) elevates cytosolic calcium levels by
      emptying intracellular calcium stores and stimulates a biphasic calcium influx.
      Activation of platelet cAMP- and cGMP-dependent protein kinases inhibits the ADP-
      and thrombin-evoked, calcium store-associated cation influx, but not the fast
      receptor operated cation influx induced by ADP. Experiments with various ADP
      analogs, ATP and ATP-gamma-S suggest that two different ADP-receptors may mediate
      the calcium responses in human platelets.

PMID- 8268710
TI  - Dual diagnosis: an annotated bibliography of recent research.

PMID- 8268711
TI  - The social validity of an argument supporting a ban on aversive procedures.
AB  - There is currently a controversy regarding the use of non-aversive and aversive
      procedures in the treatment of severe behaviour problems in individuals with
      mental retardation. One specific criticism directed at professionals who support
      the non-aversive position is that they have taken quotations from scientific
      articles out of context in order to give the impression of empirical support for
      their position. The present authors addressed this issue by assessing the social
      validity of references made to selected scientific articles in support of a
      specific argument in a monograph by Guess et al. (1987). Three groups of
      individuals were surveyed in this study: (1) psychologists working with
      individuals with mental retardation at six state schools in Texas (Group I); (2)
      selected professionals with expertise in the area of self-injurious behaviour and
      in the use of behaviour modification techniques with individuals who are mentally
      retarded (Group II); and (3) the authors of the six journal articles that were
      selected for the present study (Group III). The study focused on references made
      to journal articles in support of the 'depersonalization hypothesis' that
      aversive therapies serve to depersonalize the recipients of these treatments.
      Results indicate that the authors of the monograph were not completely accurate
      in their references to the six articles. Sixty per cent of the respondents from
      Group I, 71% of respondents from Group II, and two out of the three respondents
      from Group III rated the citations made in the monograph as inaccurate. In
      addition, the respondents rated the articles as not supportive of the
      depersonalization hypothesis for which they were cited. Over half of Group I
      respondents, and all respondents from Groups II and III rated the articles as non
      supportive of the depersonalization hypothesis. These findings suggest that the
      authors of the monograph have used references selectively and incorrectly in
      support of their views in at least some instances. This emphasizes the importance
      of critical reading and hypotheses based on bodies of knowledge rather than
      selected sources. Furthermore, this study indicates the need for operationally
      defined hypotheses which may be examined empirically.

PMID- 8268712
TI  - Prefrontal neocortical disturbances in mental retardation.
AB  - Morphometrical analysis of the frontal lobe neocortex of seven selected cases of
      mental retardation of unclassified aetiology and pathology, showing mild
      dysplastic changes of the neocortex on routine workup, were compared with nine
      normal controls and seven cases with Down's syndrome. In comparison with the
      normal controls, the group with 'unclassified' mental retardation showed an
      increased percentage of disoriented pyramidal neurons in layers III and IV-V (8
      17%, P < 0.01), an abnormal distribution of small pyramidal cells with a shift
      from superficial to deeper layers of the prefrontal cortex (P < 0.01), and an
      increased cortical thickness (+38%, P < 0.05) of Brodmann area 10, as well as a
      tendency to a decreased gyration of the frontal lobe sulci (-14%, P = 0.18).
      However, no statistically significant macroscopical differences either in frontal
      lobe gyration or in the size of the cerebrum and its frontal lobes were found
      between these two groups. On the other hand, the Down's syndrome group had a
      significantly decreased gyration (-36%, P < 0.01). These findings may indicate an
      inhibited and disordered migration of putative small pyramidal neurons in cases
      of 'unclassified' mental retardation.

PMID- 8268713
TI  - Visual problems in people with severe mental handicap.
AB  - The incidence of visual problems in people with mental handicaps is very high.
      Nine severely mentally handicapped patients were studied. Several objective and
      subjective optometric tests were performed. The results showed the presence of
      different kinds of visual problems that were compensated for by optical methods.
      The subjects showed a general change in their behaviour. It is essential to give
      optometric care to such people.

PMID- 8268714
TI  - Growth and developmental patterns in Prader-Willi syndrome.
AB  - Eleven Japanese patients with Prader-Willi syndrome were studied from infancy,
      and examined with respect to their growth and development. The chromosomal
      aberration was observed in 40% of the patients using a high-resolution chromosome
      banding technique. The birth weight in 10 out of the 11 patients was below the
      mean and the rate of body weight gain was severely retarded by 6 months in all
      cases, which suggested an insufficient utilization of nutrients in uterine life
      and in early infancy. The rate of height increase as well as that of body weight
      increase were also transiently retarded from 10 to 18 months of age in eight
      cases, and the body weight gain increased dramatically after 10-18 months due to
      hyperphagia. The patients' mean milestones of development were delayed (the mean
      developmental quotient was 50) in comparison with those of control patients;
      there was no difference between the developmental milestones of the two groups
      with and without the chromosomal aberration.

PMID- 8268715
TI  - Role of function-associated molecules in target cell lysis: analysis of rat
      adherent lymphokine-activated killer cells.
AB  - Monoclonal antibodies (MAbs) against fish nonspecific cytotoxic cells (NCC)
      inhibit the lysis of target cells by NCC and by human and rat natural killer (NK)
      cells. We now show that the anti-function-associated molecule (anti-FAM) MAb 5C6
      also inhibits the cytolytic activity of rat (F344) nonadherent lymphokine
      activated killer (LAK) cells and adherent LAK (ALAK) cells. Rat nylon-wool
      nonadherent (NWNA) cells were cultured for 48 h in recombinant human interleukin
      2 (IL-2). Nonadherent cells were then removed and the plastic-adherent (ALAK)
      cells were recultured for 9 days. Cells were daily analyzed by cytometry (using
      MAb 5C6 and the rat NK cell MAb 3.2.3) and cytotoxicity. Approximately 40% of the
      initially cultured NWNA cells, 50-60% of the LAK cells and 87-98% of the ALAK
      cells were positive for MAb 5C6. Tissue culture supernatants containing MAb 5C6
      caused a dose-dependent inhibition of cytotoxicity against P815 and YAC-1
      targets. Approximately 50% inhibition was obtained at MAb concentrations of 1.25
      2.5 micrograms/ml. Maximum inhibition of ALAK cytotoxicity was 86% on day 4 of
      culture. Two-dimensional SDS-PAGE and Western blot analysis of acetone
      precipitated cell membrane preparations identified a 55-kD molecule (pI 6.1-6.3)
      on NWNA and ALAK cells and an additional slightly more acidic 45-kD protein on
      ALAK cells. These data indicate that rat ALAK cells may initiate lysis of target
      cells via receptor binding.

PMID- 8268716
TI  - Proliferation of erythromycin-stimulated mouse peritoneal macrophages in the
      absence of exogenous growth factors.
AB  - Erythromycin (0.2-20 micrograms/ml) induced the proliferation of macrophages of
      mouse peritoneal exudate cells (PEC) in a liquid medium without exogenous growth
      factors. The proliferating macrophages formed giant colonies between days 22 and
      26 of culture; these colonies continued to proliferate even after subculture. The
      erythromycin-induced cell proliferation was independent of fibroblasts, T cells,
      B cells, or endotoxins. This activity seemed to be specific to erythromycin since
      other antibiotics such as tetracycline, streptomycin, gentamicin, penicillin G,
      and josamycin did not induce the proliferation of macrophages. Any known
      cytokines, including IL-2, IL-3, IL-4, IL-6, and GM-CSF, were not detectable by
      ELISA tests in any of the culture supernatants sampled from day 7 through day 28.
      The culture supernatants, however, had the capability of inducing the growth of
      macrophages, only in the presence of bioactive erythromycin at concentrations
      higher than 1.6 micrograms/l. Moreover, the culture supernatants, sampled after
      giant colonies had been formed, were capable of inducing giant colonies in the
      culture of adherent PEC. Thus, the erythromycin-induced macrophage proliferation
      might be due to the direct effect of this antibiotic, whereas the formation of
      giant colonies might be due to the production of some unidentified soluble factor
      produced by the proliferating macrophages. These data indicate that mouse PEC
      contain a subset of peritoneal macrophages capable of responding to erythromycin
      by forming proliferating colonies without exogenous growth factors.

PMID- 8268717
TI  - How does influenza virus regulate gene expression at the level of mRNA
      translation? Let us count the ways.

PMID- 8268718
TI  - Diverse molecular mechanisms of inhibition of NF-kappa B/DNA binding complexes by
      I kappa B proteins.
AB  - The activity of the rel/NF-kappa B/dorsal family of kappa B site binding proteins
      is regulated by I kappa B proteins. The ankyrin repeat motif identified I kappa B
      family members, which include I kappa B alpha (pp40/MAD-3), I kappa B gamma, and
      bcl3, directly associated with kappa B site binding proteins, resulting in
      specific DNA-binding inhibition of rel, p50, or p65 dimers. We report that I
      kappa B gamma, containing eight ankyrin repeats, mediates a reversible inhibition
      of (p50)2-DNA complex but cannot displace preformed DNA-protein complexes. I
      kappa B alpha and bcl3, on the other hand, can displace preformed DNA-protein
      complexes. I kappa B alpha specifically displaces (p65)2 or p50/p65-DNA complexes
      but requires the C-terminal 37 amino acids in addition to the ankyrin repeat
      domain. Human bcl3 protein specifically displaces (p50)2-DNA complexes. Because I
      kappa B alpha and bcl3 can displace preformed (p65)2 or (p50)2-DNA complexes,
      respectively, we propose that they can act as repressors or antirepressors of NF
      kappa B-induced gene expression.

PMID- 8268719
TI  - Analysis of the promoter element of the serum amyloid A gene and its interaction
      with constitutive and inducible nuclear factors from rabbit liver.
AB  - In an effort to identify regulatory elements of the serum amyloid A (SAA) gene
      that play a major role in its expression under acute-phase conditions, we studied
      the expression of a set of chimeric SAA-chloramphenicol acetyltransferase (CAT)
      plasmids containing a progressively deleted upstream 5' sequence of the SAA gene.
      Two regulatory regions (-314 to -135 and -135 to -31) capable of driving cytokine
      induced transcription have been identified. Gel retardation assays revealed that
      the regulatory region located between positions -314 and -135 is a major site of
      interaction for highly inducible and constitutive nuclear proteins in acute-phase
      rabbit liver. DNase I footprint and competition analyses showed that this region
      contains two adjacent nuclear protein binding sites (between -191 and -140) with
      varying affinity for protein binding. Both of these binding sites are capable of
      driving cytokine-induced transcription of a reporter gene containing a minimal
      promoter. Detailed analyses of the inducible nuclear proteins that bind to this
      promoter element showed that they are homologues of the CCAAT/enhancer binding
      protein (C/EBP) family. Accumulation of the inducible nuclear factors under acute
      conditions, when maximal transcription activity has been reported, suggests a
      critical role for these proteins in the expression of the SAA gene.

PMID- 8268720
TI  - Molecular organization of the rat glia-derived nexin/protease nexin-1 promoter.
AB  - The first three exons and the promoter of rat glia-derived nexin, also called
      protease nexin-1 (GDN/PN-1), have been identified through analysis of rat genomic
      clones. A 1.6 kilobase (kb) fragment containing 105 base pairs of the first exon
      and 5'-flanking sequences was sequenced. The 5'-flanking sequence and the first
      exon were found to be GC-rich, indicating that the 5' region of the rat GDN/PN-1
      gene resides within a CpG island. A TATA box-like sequence, but no CAAT box, was
      found. The rat GDN/PN-1 promoter contains five SP1 consensus sites, four
      consensus sites for the MyoD1 transcription factor, and one binding site for the
      transcription factors NGFI-A, NGFI-C, Krox-20, and Wilms tumor factor. The
      presence of these consensus sequences is consistent with the known expression
      pattern of GDN/PN-1. Primer extension and RNase protection assays identified one
      transcriptional start site. The 1.6 kb promoter fragment cloned in a reporter
      plasmid was found to induce firefly luciferase expression in a cell-specific
      manner. A positive regulatory element is localized in the region -1545 to -389.
      In vitro CpG methylation blocked transcription from the GDN/PN-1 promoter in rat
      hepatoma cells but not in C6 rat glioma cells.

PMID- 8268722
TI  - Duchenne muscular dystrophy--Meryon's disease.
AB  - In a communication to the Royal Medical and Chirurgical Society of London in
      December 1851, which was published in the Transactions of the Society the
      following year, Edward Meryon, an English physician, described, in considerable
      detail, eight boys in three families with a disease later referred to as Duchenne
      muscular dystrophy. He was particularly impressed by the predilection for males
      and its familial nature, and that the progressive muscle wasting and weakness was
      essentially due to a disease of muscle and not the nervous system. His detailed
      histological studies revealed no abnormality of the spinal cord or nerves but in
      muscle tissue he noted extensive "granular degeneration" and in particular that
      the sarcolemma was broken down and destroyed. He appears to have been the first
      physician to make a detailed clinical, genetic, and pathological study of the
      disorder several years before Duchenne.

PMID- 8268721
TI  - The two functionally distinct amino termini of chicken c-ets-1 products arise
      from alternative promoter usage.
AB  - The chicken c-ets-1 locus gives rise to two distinct transcription factors
      differing by structurally and functionally unrelated N-termini. p54c-ets-1 shows
      a striking phylogenetic conservation from Xenopus to humans, while p68c-ets-1,
      the cellular counterpart of the E26-derived v-ets oncogene, is apparently
      restricted to avian and reptilian species. In the chick embryo, both mRNAs are
      expressed in a wide array of tissues of mesodermal origin; however, in the embryo
      and after hatching, p68c-ets-1 is excluded from lymphoid cells where p54c-ets-1
      accumulates. In this report, we define the basis of the differential expression
      of the chicken c-ets-1 products to assess their different potentials as
      transcription factors. We demonstrate that the two distinct N-termini arise from
      alternative promoter usage within the chicken c-ets-1 locus. Examination of both
      promoters reveals that transcription initiates from multiple sites, consistent
      with the absence of TATA and CAAT elements. Of these two regulatory regions, only
      the one that initiates the p54c-ets-1 mRNA synthesis is of the G + C-rich type,
      and its organization is conserved in humans. The avian-specific p68c-ets-1
      promoter activity was enhanced by its own product. In addition, we identify
      numerous potential binding sites for lymphoid-specific transcription factors that
      might contribute to a tight repressor effect in lymphoid tissues.

PMID- 8268723
TI  - Development of electrical myotonia in the ADR mouse: role of chloride conductance
      in myotubes and neonatal animals.
AB  - In the ADR mouse, the homozygous condition of the autosomal mutation adr,
      "arrested development of righting response", leads to the symptoms of myotonia.
      The adr mutation is caused by an insertion of a retroposon into a gene for a
      chloride channel (adr = Clc-1) that is expressed in adults, but only at very low
      levels in neonate rodent muscle. In the present study, we investigated the
      earliest stages of the ADR myotonia. In muscle from 7-day-old ADR mice that can
      be recognized by inspection, electrical after-activities are distinct by their
      low frequency (1-5 Hz) and long duration (several minutes) from those recorded in
      adult muscle. Similar myotonic symptoms could be evoked in muscle fibres from 7
      day wildtype mice after substitution of the external chloride with impermeant
      anions or by activators of protein kinase C. The genotypes of 3-day-old mice
      cannot be inferred from inspection and, thus, were identified by Southern
      blotting with a ClC-1 probe. Although no +/+ animal showed characteristic
      myotonic series, these were seen both in adr/adr and in most adr/+ animals. Thus,
      due to the low dosage of chloride channels in 3-day-old mouse muscle, the adr
      mutation appears to be partially dominant rather than fully recessive, as in
      adult mice. No indication of electrical myotonia could be demonstrated in
      cultured myotubes, although their pattern of excitability depended on the
      presence of external chloride ions. We conclude that the low Cl(-)-conductance of
      myotubes influences excitability but is not controlled by the adr/Clc-1
      gene.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268724
TI  - Retrovirus-mediated gene transfer of transthyretin and transthyretin-methionine
      30: a potential tool for the study of amyloidogenesis.
AB  - Familial amyloidotic polyneuropathy (FAP) is a genetic disease characterized by
      systemic amyloid deposition particularly in the peripheral nervous system. These
      deposits are composed mainly of a mutant form of the serum protein transthyretin
      (TTR) having a methionine for valine substitution at position 30-TTR Met 30. The
      factors involved in the formation of these deposits are unknown. The existence of
      animal models for FAP should allow elucidation of these factors. As one approach
      to the development of animal models for amyloidogenesis in FAP, we have
      constructed recombinant retrovirus vectors, carrying the full length human cDNA
      for either TTR or TTR Met 30 under the control of the Moloney murine leukemia
      virus (MoMLV) LTR element. After transfection of the packaging cell line, psi 2,
      viral stocks were used to infect a rat hepatoma cell line, H56, mouse fibroblast
      cell line, NIH3T3, and mouse primary fibroblasts. H56 cells efficiently secreted
      both TTR and TTR Met 30 as assessed by immunoprecipitation and ELISA, whereas
      NIH3T3 fibroblasts appeared not to release these proteins under the conditions
      tested. Primary fibroblasts secreted the mutant protein as assessed by ELISA.
      These genetically modified cells can be grafted into animals for in vivo study of
      amyloidogenesis, as well as be used in culture to investigate factors that might
      regulate the rate of amyloid deposition.

PMID- 8268725
TI  - Ubiquitin and beta-amyloid-protein in inclusion body myositis (IBM), familial IBM
      like disorder and oculopharyngeal muscular dystrophy: an immunocytochemical
      study.
AB  - We used immunocytochemistry to identify ubiquitin and beta-amyloid-protein in
      muscle biopsies from patients with three neuromuscular disorders characterized by
      the presence of rimmed vacuoles in muscle fibres: inclusion body myositis (IBM),
      familial IBM-like disorder and oculopharyngeal muscular dystrophy (OPMD).
      Labelling with anti-ubiquitin antibodies was observed in all three diseases, but
      it was frequent in IBM, less common in familial IBM-like disorder and rare in
      OPMD. This labelling is thought to correspond to the presence of IBM-type
      filaments (16-18 nm in external diameter) which are characteristic but not
      specific for IBM or familial IBM-like disorder, as they may also occur in other
      diseases including OPMD. Labelling with anti-beta-amyloid-protein antibody was
      seen in a few fibres in IBM but not in the other two conditions. The structures
      labelled with this antibody have yet to be determined. Labelling with anti
      ubiquitin or anti-beta-amyloid-protein antibodies was not correlated with the
      presence of acid phosphatase activity.

PMID- 8268726
TI  - Myopathy of the Proteus syndrome: hypothesis of muscular dysgenesis.
AB  - The Proteus syndrome is a congenital disorder of growth regulation affecting
      tissues of mesodermal and ectodermal origin. It is expressed as hemihypertrophy,
      hemimegalencephaly, muscular overgrowth, verrucous epidermal nevi, haemangiomas
      and bony dysplasias. Muscle biopsies were examined at 7 and 10 yr of age from a
      girl with this disease. Several cytoarchitectural alterations of myofibres,
      proliferation of sarcolemmal nuclei, and other myopathic changes were
      demonstrated in regions adjacent to other with normal myofibres; the boundaries
      did not correspond to fascicular margins. A perinuclear and subsarcolemmal
      distribution of excessive desmin was also found. It is suggested that this
      myopathy represents a new category of neuromuscular disease, "muscular
      dysgenesis", due to faulty paracrine growth factors.

PMID- 8268727
TI  - Degradative activity of granzyme A on skeletal muscle proteins in vitro: a
      possible molecular mechanism for muscle fiber damage in polymyositis.
AB  - The importance of cytotoxic T lymphocytes (CTLs) in the autoimmune inflammatory
      myopathies, especially polymyositis (PM), has been emphasized. We have studied
      the degradative activity of granzyme A, a cytotoxic molecule with trypsin-like
      specificity in CTL granules, on several muscle proteins in vitro. Our study
      reveals that granzyme A hydrolyzes dystrophin, myosin, and nebulin, but not
      laminin, alpha-actinin, vinculin, and connectin in vitro. Among these proteins,
      nebulin is more susceptible to proteolysis, followed by dystrophin, myosin heavy
      chain, and myosin light chains, in that order. This result implies an important
      role of granzyme A in CTL-mediated muscle fiber damage in PM.

PMID- 8268728
TI  - Monomelic muscle atrophy.
AB  - Two patients with slowly progressive muscle atrophy limited to only one leg are
      reported. They had pes equinovarus deformity and muscle weakness in the affected
      leg but no symptom in the other limbs. Muscle biopsies from the affected leg
      showed dystrophic changes consisting of variation in muscle fiber size,
      endomysial fibrosis, and necrotic and regenerating fibers. Dystrophin was
      normally expressed at the surface membrane of the muscle fibers. These two
      patients possibly had a variant of distal muscular dystrophy, though a neural
      influence could not be completely excluded.

PMID- 8268729
TI  - Evaluation of electrophysiological and clinical tests in an exploratory trial of
      Org 2766 in motor neuron disease.
AB  - Twenty four patients with motor neuron disease (MND) participated in a double
      blind, placebo-controlled trial with the ACTH 4-9 analog, Org 2766. Patients were
      examined three times during an 8 week treatment period, using a summated score
      for several manually and functionally tested muscles (sum score), myometry,
      jitter, fibre density (FD), macro motor unit potential (MUP), and supramaximal
      evoked muscle action potentials. No differences were found between Org 2766 and
      placebo treated patients. In an open 1 yr follow-up study, 5 out of 13 patients
      treated with Org 2766 died; the others showed continued progression of weakness.
      The methods used for assessment of muscle function were compared. The highest
      interest reliability was obtained in the sum score and myometry. Mean differences
      that might be detectable were relatively small for the sum score and myometry,
      and large for FD and MUP. We concluded that clinical function testing and
      myometry are superior to electromyographic measurements for assessment of changes
      in MND patients.

PMID- 8268730
TI  - Linkage and apparent heterogeneity in proximal spinal muscular atrophies.
AB  - Linkage studies with 9 highly informative DNA markers on the long arm of
      chromosome 5 were performed in 12 multiplex families (29 patients) with spinal
      muscular atrophy (SMA) from The Netherlands. The results of the linkage analysis
      were compatible with localization of a major SMA gene in the chromosomal region
      5q12-13. By minimum recombinant analysis the most likely position of the SMA
      locus was between loci D5S6/D5S125 and D5S112/MAP1B, which is in agreement with
      several linkage studies from other countries. In four families, however, more
      than one crossover between SMA and a flanking DNA marker appeared, and in one
      family the observed hybridization phenotype for the markers closely flanking the
      SMA locus was identical for an unaffected individual and for his two affected
      sibs with SMA type III. For this latter family, among several explanations the
      most likely are either the presence of a double crossover or linkage
      heterogeneity.

PMID- 8268732
TI  - Neuromuscular disorders: gene location.

PMID- 8268731
TI  - Arthrogryposis multiplex in a newborn of a myasthenic mother--case report and
      literature.
AB  - About 12% of children of myasthenic mothers exhibit a transitory myasthenic
      syndrome. Usually, these symptoms have disappeared after a few weeks. Treatment
      with anticholinesterase drugs is successful. The purpose of this paper is to
      present an infant born to a myasthenic mother, with distal arthrogryposis, severe
      hypotonia and respiratory distress, unresponsive to administration of
      pyridostigmine bromide. Eleven other cases of neonatal myasthenia with
      arthrogryposis are known. Five of them were stillborn or died within the first
      day of life. The surviving children had profound weakness and needed ventilatory
      assistance for a long period. The severity of these few cases contrasts with the
      numerous reports of benign and transitory signs of neonatal myasthenia. Passively
      transferred maternal acetylcholine receptor antibodies may produce illness in the
      newborn.

PMID- 8268733
TI  - Why are we still poisoning the elderly so often?

PMID- 8268734
TI  - Debate between sport and occupational overuse injuries.

PMID- 8268735
TI  - Preventing colorectal cancer.

PMID- 8268736
TI  - [Cautionary warning].

PMID- 8268737
TI  - More to it than low blood sugar. Kason explores mystical experiences. Interview
      by Pam Harrison.

PMID- 8268738
TI  - Radiology rounds. Pectus excavatum.

PMID- 8268739
TI  - Leadership as paradigms change. Challenges and opportunities.

PMID- 8268740
TI  - The jumpy janitor. Letter to an ethicist.

PMID- 8268741
TI  - Potentially undesirable prescribing and drug use among the elderly. Measurable
      and remediable.
AB  - Forty-seven patients older than 65 years were randomly selected for structured
      chart review of all long-term medications documented during the prior year and
      the number of instances of potentially undesirable prescribing for each patient.
      A trained nurse subsequently made home visits to assess all long-term medications
      used regularly during the same period. Forty-five percent of elderly patients had
      one or more instances of potentially undesirable drug use, all of which appeared
      to be readily remediable. Commercial drug interaction software identified less
      than half of the potentially undesirable instances.

PMID- 8268742
TI  - Do topical antibiotics help corneal epithelial trauma?
AB  - Topical antibiotics are routinely used in emergency rooms to treat corneal
      trauma, although no published evidence supports this treatment. In a
      noncomparative clinical trial, 351 patients with corneal epithelial injuries were
      treated without antibiotics. The infection rate was 0.7%, suggesting that such
      injuries can be safely and effectively managed without antibiotics. A comparative
      clinical trial is neither warranted nor feasible.

PMID- 8268743
TI  - Ethical concerns in HIV testing.
AB  - I conducted a retrospective chart review of all HIV antibody test requests
      received in the laboratory of a community hospital. Despite guidelines calling
      for pre-test counseling and informed consent, only one test request noted patient
      consent. Less than 40% documented a physician's order. This article reviews
      guidelines and suggests ways to improve practice.

PMID- 8268744
TI  - Care of asthma. A personal approach.
AB  - I describe an approach to managing asthma in a family practice office. The
      approach is divided into stages: gaining control of the asthma, educating the
      patient, and maintaining the improvement. Patients are encouraged to take control
      and work with me to manage the asthma. Regular follow up is important.

PMID- 8268745
TI  - How to manage burns in primary care.
AB  - Burns are common injuries; more than 200,000 occur in Canada annually. Nearly all
      burn injuries can be managed on on outpatient basis. Appropriate treatment
      depends on burn depth, extent, and location. Special types of burns, such as
      chemical, tar, and electrical injuries, need specific management strategies.
      Prevention through education is important to reduce the incidence of burns.

PMID- 8268746
TI  - Noninvasive blood flow tests in vascular disease.
AB  - Noninvasive testing is now routine for assessing vascular conditions. Many
      noninvasive tests are available for obtaining physiologic and anatomic
      information that is both precise and reproducible. This paper discusses
      noninvasive testing with plethysmography, Doppler ultrasonography, and duplex
      scanning for carotid artery occlusive disease, deep venous thrombosis, and
      peripheral arterial occlusive disease.

PMID- 8268747
TI  - [Treatment of depression in the elderly. The use of psychostimulants].
AB  - Classical treatment of depression in the elderly is often complicated by side
      effects and delayed therapeutic effect. After reviewing the literature and their
      clinical experiences, the authors suggest several acceptable indications for the
      use of psychostimulants in the elderly, especially when the depression is
      associated with a serious physical illness.

PMID- 8268748
TI  - Computerizing the modern physician's office. A practical guide.

PMID- 8268749
TI  - Human immunodeficiency virus revisited.

PMID- 8268750
TI  - Monoclonal antibodies that recognize antigens in human osteosarcoma cells and
      normal fetal osteoblasts.
AB  - Four monoclonal antibodies (HOB-1-4) that react against human osteosarcoma cells
      (Saos-2) and human fetal osteoblasts in situ were developed by immunizing mice
      with Saos-2 cells. HOB-1 (IgG1, k) and HOB-2 (IgM, k) stain cytoplasmic antigens
      in Saos-2 cells, human authentic osteoblasts and occasional cells in liver,
      spleen and, in the instance of HOB-1, kidney and adrenal gland. On Western
      blotting of Saos-2 cell lysates, HOB-1 recognizes a single protein species of
      M(r) 59,000, while HOB-2 reacts with a different species of M(r) 57,000. HOB-3
      (IgG1, k) stains a cell membrane associated antigen in Saos-2 cells and
      osteoblasts in situ. The reaction pattern of this antibody is virtually identical
      to that seen in alkaline phosphatase (ALP)-positive cells in all organs examined
      immunohistochemically, except for intestinal epithelium. Both immunoblotting and
      immunoprecipitation analyses confirm that the antigen detected by HOB-3 is ALP.
      HOB-4 (IgG1, k) reacts weakly against Saos-2 cells cultured under standard
      conditions, but strongly following the exposure of the cells to the secretory
      inhibitor monensin. On frozen section screening, this antibody reacts
      preferentially with the collagenous extracellular matrix not only of the
      periosteum but of other tissues and organs as well. The precise identity of the
      HOB-4 antigen remains to be established. We suggest that these four monoclonal
      reagents will be useful adjuncts in characterizing the osteoblastic phenotype.

PMID- 8268751
TI  - Phosphate metabolism in the red cell of sick prematures.
AB  - The effect of different amounts of phosphorus supplementation on phosphate
      metabolism was studied in two groups of sick preterms (B and C) during the first
      week of life. Group B included prematures that started formula milk feeding from
      day 3 and group C neonates on total parenteral nutrition with phosphate
      supplementation for 7 days. Twelve healthy preterm neonates on formula milk
      feeding from day 2 (group A) were used as controls. On the 7th day of life all
      phosphate parameters measured in group C (plasma and red cell inorganic phosphate
      and erythrocyte ATP and 2,3-diphosphoglycerate) were found significantly lower
      than in the controls (1.60 +/- 0.07; 0.60 +/- 0.08; 1.45 +/- 0.09 and 4.42 +/-
      0.18 vs. 2.05 +/- 0.10; 0.94 +/- 0.11; 1.69 +/- 0.07 and 6.24 +/- 0.42 mmol/l,
      respectively). The renal tubular reabsorption of phosphate was also lower in this
      group (86.8 +/- 3.2 vs. 97.3 +/- 1.0%). No significant differences were observed
      between groups B and A. Higher phosphorus intake that was better achieved through
      early milk feeding prevented phosphate depletion and the decline of 2,3
      diphosphoglycerate in the erythrocytes even of sick neonates which in turn might
      help to improve tissue oxygenation. The amount of parenteral phosphate
      supplementation that could have beneficial effects on red cell phosphate
      parameters needs further investigation.

PMID- 8268752
TI  - Expression of bone protein mRNA at physiological fluoride concentrations in rat
      osteoblast culture.
AB  - Fluoride causes an increase in the amount of unmineralized osteoid. To determine
      whether the increase in osteoid is due to greater protein expression in the
      presence of fluoride, we measured the relative amount of mRNA expressed by fetal
      rat calvaria cells maintained in culture for either 18 or 26 days in the presence
      of 0, 5, 20 or 300 microM fluoride. There were no differences in the level of
      expression of mRNA for collagenous or non-collagenous proteins in fluoride
      treated cells as compared with control cells at 18 days in culture. Expression of
      mRNA for osteocalcin and alpha 1-type 1 collagen was decreased at 300 microM
      fluoride after 26 days culture. The amount of [3H]thymidine incorporation in
      cells exposed to the different amounts of fluoride was measured at various time
      points. Fluoride did not alter the time at which rapid cell proliferation ended.
      These studies indicate that at physiological serum levels, fluoride does not
      increase expression of mRNA by osteoblasts. The relative increase in osteoid in
      bone may be related to other mechanisms such as altered matrix mineralization.

PMID- 8268753
TI  - Immunological evidences for post-translational control of the parathyroid
      function by ionized calcium in dogs.
AB  - To outline the role of post-translational events in the control of the
      parathyroid function in vivo, we have studied the parathyroid function of normal
      dogs receiving i.v. infusions of CaCl2 and Na2EDTA with intact (I),
      carboxylterminal (C) and midcarboxylterminal (M) iPTH assays and evaluated the
      influence of ionized calcium on circulating molecular forms of iPTH via
      alterations in C/I, M/I and M/C iPTH ratios. Furthermore, the use of the
      mathematical model fitting the sigmoidal relationship between ionized calcium and
      iPTH ratios was improved through the generation of more iPTH ratio points in the
      ascending part of the sigmoid function. Quantitatively, the response to
      hypocalcemia was highest with M (98.7 +/- 36.8 pmol/l; P < 0.0167 vs. L and P <
      0.0001 vs. I) and higher with L (83.1 +/- 26.1 pmol/l; P < 0.0001 vs. I) than
      with I (12.1 +/- 3.2 pmol/l). Similar results were observed for the non
      suppressible fraction of iPTH measured by the three iPTH assays in hypercalcemia.
      The slope of the sigmoid function was more acute for I than for C or M, while all
      three secretion set-points were similar at 1.30 mmol/l. Qualitatively, all iPTH
      ratios increased from hypo- to hypercalcemia, results being more pronounced for
      the M/I and C/I iPTH ratios (7.66 +/- 2.57 to 73.9 +/- 41.4 and 6.76 +/- 1.93 to
      49.8 +/- 27.5) than for the M/C iPTH ratio (1.24 +/- 0.48 to 1.82 +/- 1.16). The
      slopes of the three ratios were similar as were the set-points, but in this last
      case, values were higher (1.40 mmol/l) than for secretion set-points. These
      results indicate that dog parathyroid function is similar to that of man. The
      lower set-points for secretion and higher ones for regulating M/I and C/I iPTH
      ratios favor an optimal amount of I in face of decreasing ionized calcium and
      permit to control the non-suppressible fraction of iPTH secretion via M and C
      fragments production in face of increasing ionized calcium. These events are
      important to understand the implication and signification of post-translational
      events in the parathyroid glands and in peripheral blood in the phenomenon of PTH
      immunoheterogeneity. They further outline that the tools used here will be useful
      to study similar phenomenons in individuals in face of diseased parathyroid
      glands.

PMID- 8268754
TI  - In vivo effects of transforming growth factor-beta 2 in ovariectomized rats.
AB  - In vitro studies indicate that transforming growth factor-beta (TGF-beta) has a
      role in the regulation of bone cell activities. However, little is known about
      the effects of TGF-beta on bone when it is administered systemically. This study
      was undertaken to evaluate the in vivo effects of TGF-beta 2 on bone and marrow
      cells in the ovariectomized rat bone loss model. Female Sprague-Dawley rats, aged
      95 days, were divided into 4 groups. Group 1 was sham operated; groups 2-4 were
      ovariectomized. Groups 3 and 4 received daily injections of 10 micrograms and 50
      micrograms of TGF-beta 2/kg body weight, respectively. Groups 1 and 2 received
      the solvent vehicle. All animals were sacrificed after 35 days. Ovariectomy
      caused a significant increase in, total mononuclear marrow cells, the number of
      TRAP positive multinucleated cells formed in culture of marrow cells, and the
      number of trabecular osteoclasts and osteoblasts. These increases were associated
      with loss of cancellous bone in the proximal tibia. TGF-beta 2 completely
      prevented the increase in the number of TRAP positive multinucleated cells, and
      caused a small but not statistically significant decrease in the number of
      trabecular osteoclasts. However, TGF-beta 2 had no significant effect on the
      number of total mononuclear marrow cells and on the loss of cancellous bone due
      to ovariectomy. We conclude that TGF-beta 2 probably plays a role in the
      regulation of the proliferation of osteoclast progenitors in bone marrow in vivo.
      Studies carried out over a longer period are required to determine whether it
      will modulate the increase in osteoclast and osteoblast numbers that occur in
      cancellous bone following ovariectomy.

PMID- 8268755
TI  - Application of computer-based histomorphometry to the quantitative analysis of
      methylprednisolone-treated adjuvant arthritis in rats.
AB  - Analyses of paw edema and histomorphometry were performed on tibio-talar joints
      to determine arthritic pathological responses in untreated 28-day adjuvant
      induced polyarthritis (AIP) rats, and to determine the drug effect on inhibiting
      these responses in AIP rats treated with methylprednisolone. Histomorphometric
      measurements were performed on regions including articular joint space, synovial
      tissue, articular and epiphyseal cartilage, epiphyseal and metaphyseal bone
      marrow, and endosteal and periosteal cortical bone surfaces. Analysis of paw
      edema indicated that paw volume was significantly increased in untreated AIP
      rats. This increase in paw volume was partially prevented in AIP rats treated
      with 0.3 mg methylprednisolone/kg per day, and completely prevented in AIP rats
      treated with the two higher dose levels (1 and 3 mg/kg per day).
      Histomorphometric analysis of untreated AIP tibio-talar joints showed decreased
      articular joint space whereas synovial tissue area increased and a minor, but
      significant, articular cartilage erosion area occurred. Epiphyseal growth
      cartilage area was decreased. Trabecular bone area in distal tibial epiphyseal
      and metaphyseal regions was markedly decreased whereas bone marrow area increased
      involving a large number of macrophages and osteoclasts. Eroded endocortical bone
      area was increased while cortical bone area decreased. Marked osteophyte
      proliferation occurred on the periosteal surface. These arthritic pathological
      changes were inhibited by the treatment of methylprednisolone in a dose-dependent
      fashion. The animals treated with the highest dose of methylprednisolone complete
      prevented the development of the AIP-induced pathological changes. These data
      confirmed qualitative histological evaluation of arthritic changes but did not
      correlate with the anti-edema effects of methylprednisolone (100% inhibition at
      1.0 and 3.0 mg/kg, p.o.). It is suggested that quantitative histomorphometry be
      used to determine more precisely the AIP rat model and the effects of drugs on
      different histopathological features in this experimental model of arthritis in
      preference to paw edema which gives a more limited picture of the arthritic
      response.

PMID- 8268756
TI  - Immunological evidence for the localization of a 110 kDa poly(A) binding protein
      from rat liver in nuclear envelopes and its phosphorylation by protein kinase C.
AB  - We have purified a 110 kDa poly(A) binding protein (P110) from rat liver which is
      thought to be involved in mRNA translocation through the nuclear pores and have
      demonstrated its localisation in the nuclear envelope using polyclonal antibodies
      and confocal laser scanning microscopy. Although P110 was prepared from highly
      purified nuclear envelopes, the polyclonal antibodies raised against them bind to
      nucleo- and cytoplasmic structures to a minor extent, but not to nucleolar
      structures. P110 decays spontaneously into several fragments which are also
      recognized by the polyclonal antibodies. The 110 kDa polypeptide and its
      fragments were phosphorylated by a nuclear envelope kinase and this
      phosphorylation was inhibited by a monoclonal antibody against protein kinase C
      and by a specific protein kinase C inhibitor obtained from bovine brain.
      Scatchard analysis was used to determine the influence of protein kinase C
      activators and inhibitors on nuclear envelope protein phosphorylation and RNA
      binding. The data indicate a close association between the RNA translocation
      machinery (the 110 kDa protein) and protein kinase C within the nuclear envelope.
      We suggest that the fragmentation of P110 is triggered before or during mRNA
      export and is not due to nonspecific proteolysis.

PMID- 8268757
TI  - Ethanol effect on the ionic transfer through isolated human amnion. II. Cellular
      targets of the in vitro acute ethanol action and of the antagonism between
      magnesium, taurine and ethanol.
AB  - The ultrastructure of the human amniotic membrane from normal pregnancies at
      term, was studied by transmission electron microscopy. The results were analysed
      by a stereological method which indicates the ratio between the area of
      intercellular spaces (R1), microvilli (R2) and podocytes (R3) versus the cell
      area. Addition of ethanol (0.4 g/l) in the external medium decreased R1 and R3
      and had no significant effect on R2. Ethanol reduced intercellular space and
      podocyte exchange surface. Two mM MgCl2 or 2 mM taurine restored R1 and R3 to
      normal values. The cellular targets of the antagonism between Mg, taurine and
      ethanol are particularly intercellular spaces and podocytes.

PMID- 8268758
TI  - Collagen cross-linking by pyridinoline occurs in non-reversible skin fibrosis.
AB  - The extent of the covalent cross-linking of collagen molecules by pyridinoline
      was measured in skin lesions from patients with chromomycosis, a chronic fungal
      infection leading to an extensive and chronic dermal fibrosis. These data were
      compared to those collected from patients with a localized cutaneous
      leishmaniasis, an acute inflammatory process leading to an extensive and
      reversible remodelling of the extracellular matrix. The amount of the mature
      cross-linking amino acid pyridinoline increased in chromomycosis patients when
      compared to controls and was significantly higher than in leishmaniasis patients.
      These data confirm and extend our previous studies on liver fibrosis showing that
      a high level of pyridinoline is associated to irreversible fibrotic lesions. They
      also suggest that an increase in the mature collagen cross-linking by
      pyridinoline in the course of fibrosis is not restricted to liver, but might be a
      general feature of irreversible and chronic fibrosis.

PMID- 8268759
TI  - Immunogold ultrastructural localization of calpastatin, the calpain inhibitor, in
      rabbit skeletal muscle.
AB  - The ultrastructural localization of calpastatin, the endogenous inhibitor of the
      neutral calcium-dependent proteases (calpains), was investigated in rabbit
      skeletal muscle fibers using a polyclonal antibody against the 34 kDa form of the
      inhibitor isolated from rabbit. Quantitative studies by pre- and postembedding
      immunogold techniques revealed that the distribution pattern of the specific
      immunoreactivity included: 1) the sarcolemma with the adjacent cytoplasm (about 1
      micron wide); 2) the myofibrils; 3) the mitochondria and 4) the nuclei (condensed
      as well as extended chromatin). Other cell substructures, such as lysosomes and
      the intermyofibrillar cytoplasm, were substantially devoid of immunoreactivity.
      Furthermore, in accordance to previous light microscope immunohistochemical
      experiments, an extracellular (endomysial) localization of specific
      immunoreactivity was confirmed. These results favour the view, which is also
      supported by a series of biochemical evidences, that calpastatin in rabbit
      skeletal muscle is present in cell structures also containing calpains and/or
      their putative substrates. The above multiple patterns of distribution also
      suggest that the muscular calpain-calpastatin system in skeletal muscle fibers
      may play different physiological roles in the various subcellular compartments.

PMID- 8268760
TI  - A possible association of nuclear lamina with chromatin.
AB  - The nuclear lamina associated with chromatin was examined by electron microscopy.
      Nuclei isolated from rat ascites hepatoma cells were swollen in 0.2 mM EDTA (pH
      7.0) and broken by a homogenizer. The resulting nuclear fragments were dialyzed
      against 0.2 mM EDTA (pH 7.0) overnight, fixed in formalin and sedimented on grids
      by centrifugation, then stained with 2% uranyl acetate and rotary-shadowed with
      platinum-palladium. The nuclear lamina consists of two filaments, twisting
      together both the filaments associated with chromatin fiber. The single filament
      of nuclear lamina of about 31 nm in width forms certain rings of about 187 nm in
      diameter, taking a distance of about 0.37 micron in length between the
      neighbouring rings. Thus, the arrangement of rings was proposed a packing
      structure in conforming the nuclear laminar complex with chromatin.

PMID- 8268761
TI  - Microscopic localization of mercury-selenium interaction products in liver,
      kidney, lung and brain of Mediterranean striped dolphins (Stenella Coeruleoalba)
      by silver enhancement kit.
AB  - Microscopic observation, using physical development of silver, was carried out to
      localize the mercury-selenium interaction products in the organs of Mediterranean
      striped dolphins. The silver-metal reaction products were located mainly in
      hepatocytes and macrophages for liver, in proximal tubules for kidney. They were
      less abundant in lung than in liver and kidney. The result of semi-quantitative
      histochemistry tests showed that silver staining deposits were more abundant at
      relatively high metal concentrations than low metal contents, but independent of
      the metal contents. Comparisons with the most concentrated metal contents
      suggested that there might be a new complex of mercury and selenium, which could
      not be stainable by physical silver development.

PMID- 8268762
TI  - Radioautographic study on the intracellular localization of a hypolipidemic
      agent, bezafibrate, a peroxisome proliferator, in cultured rat hepatocytes.
AB  - In order to demonstrate the intracellular localization of the peroxisome
      proliferator in the hepatocytes, we have examined the localization of silver
      grains due to 14C-labelled bezafibrate in cultured rat hepatocytes by means of
      light and electron microscopic radioautography. As it results from the difference
      between chemical fixation and freeze-substitution by light microscopic
      radioautography, more numerous silver grains, about twice, were observed in
      freeze-substitution specimens in comparison with chemical fixation. On light
      microscopic radioautograms of the epoxy resin sections during each experimental
      condition, about 90% of all the silver grains were localized over the cytoplasm.
      Then, statistical significance was evaluated on grain density in the cytoplasm.
      On electron microscopic radioautograms of whole mount cultured cells, silver
      grains were localized not on the peroxisome but on the cytoplasmic matrix
      specially over the endoplasmic reticulum. From these results, it is concluded
      that bezafibrate was localized over endoplasmic reticulum. This fact suggests
      that the receptor of the peroxisome proliferator should be associated with the
      endoplasmic reticulum or that the receptor exists on the endoplasmic reticulum.
      Thus, it is demonstrated that the peroxisome proliferator acts on the endoplasmic
      reticulum of hepatocytes to proliferate peroxisomes.

PMID- 8268763
TI  - Endocytosis of lipopolysaccharide in mouse macrophages.
AB  - Lipopolysaccharide binding sites of mouse peritoneal macrophages were
      demonstrated by means of immunogold technique. Resident peritoneal macrophages
      identified by peroxidatic activity in the nuclear envelope and in the rough
      endoplasmic reticulum show moderate and constant specific binding of bacterial
      lipopolysaccharide from E. coli to cell surface structures. Labeling of
      peritoneal macrophages with LPS-gold particles (LPS-Au) at 4 degrees C followed
      by incubation of the cells at 37 degrees C permits the investigation of LPS
      endocytosis. After various incubation times LPS-Au was detected in different
      endocytic compartments. LPS was internalized via coated pits and coated and
      uncoated vesicles (5 min.). After 60 min, incubation time LPS-Au occurred in
      electron lucent endosomes, multivesicular bodies, tubulo-reticular structures and
      in lysosomes. Gold particles appeared mainly in lysosomes after a longer
      incubation time (240 min.). The results of LPS binding and internalization are in
      accordance with a postulated LPS-receptor binding.

PMID- 8268764
TI  - Effect of denervation on lamellar cells of Meissner-like sensory corpuscles of
      the rat. An immunohistochemical study.
AB  - The denervation-induced changes on S-100 protein, glial fibrillary acidic protein
      (GFAP) and vimentin immunoreactivity (IR) of the lamellar cells from cutaneous
      Meissner-like sensory nerve formations (SNF), or corpuscles, of the adult rat
      hind limb foot-pads were studied, using combined immunohistochemical and image
      analysis (optic microdensitometry) techniques. Animals were allowed to survive
      for 1, 3 and 7 days following sciatic and saphenous nerves transection. Lamellar
      cells of Meissner-like corpuscles displayed S-100 protein- and vimentin-IR, but
      not GFAP-IR. Denervation caused a marked time-dependent decrease of S-100 protein
      IR whereas vimentin-IR did not change or weakly increased. No positive GFAP-IR
      was observed in denervated SNF. These findings suggest that continuity of SNF
      with nerve fibers supplying them is necessary to maintain some of the
      immunohistochemical characteristics of the non-neuronal cells of SNF.

PMID- 8268765
TI  - The chemoprevention of cancer: directions for the future.

PMID- 8268766
TI  - Dietary intake as a risk factor for cancer of the exocrine pancreas.
AB  - Data from 149 cases with pancreatic cancer and 363 control subjects in Utah were
      obtained from proxy respondents to assess the associations between dietary intake
      and the development of pancreatic cancer. After adjusting for cigarette smoking
      status and alcohol and coffee consumption, we observed that foods containing
      large amounts of fat from all sources increased risk of pancreatic cancer in men
      [odds ratio (OR), 3.41; 95% CI, 1.59-7.29]. Further division of fat by source of
      food showed that high intake of bacon and sausages (OR for upper tertile, 2.77;
      95% CI, 1.34-5.72) as well as large intakes of fatty foods other than meat or
      dairy products (OR for upper tertile, 2.80; 95% CI, 1.33-5.89) increased risk of
      pancreatic cancer in men; high levels of intake of red meat, chicken, fish, and
      dairy foods did not increase risk of pancreatic cancer in either men or women. In
      women, fat from nonmeat and nondairy sources also increased risk of pancreatic
      cancer (OR for upper tertile, 3.44; 95% CI, 1.35-8.78). Although no protective
      effect was observed among men who consumed large amounts of fruits, vegetables,
      or high fiber foods, we did observe a protective effect in women for these foods
      (OR for upper tertile of fruit consumption, 0.37; 95% CI, 0.18-0.81; OR for upper
      tertile of vegetable consumption, 0.32; 95% CI, 0.13-0.74; and OR for upper
      tertile of fiber consumption, 0.28; 95% CI, 0.12-0.67). Findings from this study
      support the hypothesis that diets high in fat contribute to the development of
      pancreatic cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268767
TI  - A comparison of the joint effects of alcohol and smoking on the risk of cancer
      across sites in the upper aerodigestive tract.
AB  - A unified analysis of the combined effects of alcohol and smoking in cancers of
      the upper aerodigestive tract was conducted using polychotomous logistic
      regression to determine if, at the same level of exposure, risk varies
      significantly across pathological sites. Data from a case-control study in
      northern Italy include males with tumors of the oral cavity/pharynx, larynx, and
      esophagus and males admitted to the hospital for acute illnesses not related to
      alcohol and smoking. The combined alcohol and smoking risks for oral
      cavity/pharynx cancer in these data were significantly greater than those for
      either laryngeal or esophageal cancer, but esophageal cancer and laryngeal cancer
      could not be distinguished based on risk. The differences may lie in the presence
      of unspecified factors in the oral cavity and pharynx, but not in the other upper
      aerodigestive tract sites, which potentiate the effects of alcohol and smoking in
      the oral cavity/pharynx.

PMID- 8268768
TI  - A case control study of nutritional factors and cervical dysplasia.
AB  - The association of nutritional factors with cervical dysplasia was examined
      through a case-control study. Analysis was conducted in 257 cases and 133
      controls confirmed both by cytological examination and colposcopic findings. A 24
      h dietary recall questionnaire was used to assess nutritional intake. Various
      risk factors (including age at first intercourse, number of sexual partners,
      parity, cigarette smoking, oral contraceptive use, human papillomavirus type 16
      infection, and age and race) were adjusted for their potential confounding
      effects. While analyses were also performed to adjust for total calories, results
      were not changed significantly. Among the nutrients examined, vitamin A intake
      showed a significantly increased risk at the lowest quartile compared to the
      highest quartile, with an odds ratio of 2.2 (95% confidence interval, 1.2-4.2). A
      significant trend of increasing risk was also observed with lower intake of
      vitamin A (P = 0.05). Riboflavin showed increased risk at the two lower quartiles
      of intake with a trend test P value of 0.04. Increased risk was also found for
      lower intakes of vitamin C compared to the highest intake level. For folate,
      increased risk was found in the second highest quartile compared with the highest
      quartile with an odds ratio of 2.0 (95% confidence interval, 1.0-3.8). The
      calcium:phosphorus ratio showed an increased risk at the lowest level (odds
      ratio, 2.0; 95% confidence interval, 1.0-4.3). Insufficient intake of vitamin A,
      riboflavin, ascorbate, and folate is associated with an increased risk of
      cervical dysplasia.

PMID- 8268769
TI  - Prostitution, HIV, and cervical neoplasia: a survey in Spain and Colombia.
AB  - The prevalence of cervical intraepithelial neoplasia (CIN) and the association of
      CIN with prostitution was examined in Oviedo, a region in Spain with low
      incidence of cervical cancer, and in Cali, Colombia, where the incidence of
      cervical cancer is 6-10 times higher. In Oviedo, the study included 758
      prostitutes attending a sexually transmitted diseases clinic and 1203
      nonprostitutes attending a family-planning clinic. In Cali, 775 prostitutes and
      1795 nonprostitutes attending health centers were included. Seropositivity to
      common sexually transmitted agents was investigated in Spanish prostitutes. No
      significant difference was found in the prevalence of CIN between Oviedo and Cali
      in both prostitutes (2.5 versus 1.8%) and nonprostitutes (1.2 versus 1.1%).
      Prostitutes had a 2-fold increased risk of CIN as compared to nonprostitutes; in
      Spain, the prevalence odds ratio (POR) was 2.3 and the 95% confidence interval
      (CI) was 1.1-4.5, and, in Colombia, POR was 1.8 and the 95% CI was 0.9-3.5. Among
      prostitutes in Oviedo, human immunodeficiency virus (HIV) prevalence was 4.9% and
      HIV-positive prostitutes showed a high risk of CIN as compared to HIV-negative
      prostitutes (POR, 12.7; 95% CI, 3.9-40.9); 76% of HIV-positive prostitutes were
      i.v. drug users and showed an increased seroprevalence of other sexually
      transmitted diseases. HIV-negative prostitutes did not show any increased risk of
      CIN (POR, 1.2; 95% CI, 0.5-2.8). These results show that among nonprostitutes the
      prevalence of CIN was not statistically different between the two cities in Spain
      and Colombia; prostitutes were at moderate increased risk compared to
      nonprostitutes in both cities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268770
TI  - Cholangiocarcinoma: epidemiology, mechanisms of carcinogenesis and prevention.
AB  - Cholangiocarcinoma is a relatively rare cancer; worldwide it accounts for an
      estimated 15% of liver cancers. In most areas, the etiology is rather obscure,
      and identified risk factors such as hepatolithiasis, inflammatory bowel disease,
      and exposure to Thorotrast can account for only a small proportion of cases. In
      certain areas of southeast and eastern Asia, however, incidence rates are very
      high, and here there is a strong association with infection with the liver flukes
      Clonorchis sinensis and Opisthorchis viverrini. The mechanisms of carcinogenesis
      in O. viverrini infection have been the subject of considerable research; it
      seems that the presence of parasites induces DNA damage and mutations as a
      consequence of the formation of carcinogens/free radicals and of cellular
      proliferation of the intrahepatic bile duct epithelium. Preventive strategies in
      areas endemic for liver flukes appear straightforward, but breaking the cycle of
      infection has proved difficult in practice.

PMID- 8268771
TI  - Mortality trends in cutaneous malignant melanoma in Spain, 1967-1986.
AB  - The effect of age, cohort, and year of death on the mortality of cutaneous
      malignant melanoma is determined by the use of a Poisson log-linear model. During
      the period of the study, mortality due to this tumor increased exponentially (an
      annual rise of 11% in both sexes). The model attributes this rise to a cohort
      effect. The relative risk for the 1952 cohort as compared to the 1892 cohort is
      530 for men and 280 for women. In the younger generations, no signs of leveling
      off are to be seen. The sharp increase in mortality due to malignant melanoma of
      the skin has also been witnessed in other countries and suggests a real increase
      in incidence. One explanation for this epidemic phenomenon lies in the
      progressive rise in exposure to UV radiation.

PMID- 8268772
TI  - The association between cancers of the small and large bowel.
AB  - Malignant tumors of the small bowel are rare and little is known about their
      etiology, although adenocarcinomas share certain epidemiological features with
      colorectal cancer. This study investigated what cancers, if any, occurred as
      second neoplasms following adenocarcinomas, malignant carcinoid tumors,
      lymphomas, and sarcomas of the small bowel. For all 2581 cases of small bowel
      malignancy registered in one of the Surveillance, Epidemiology, and End-Results
      program areas, 1973-1988, the relative risk of a second malignancy was
      determined. The risk of colorectal cancer was increased following adenocarcinoma
      of the small bowel, and the risk of adenocarcinoma of the small bowel was
      increased following colorectal cancer in both males and females. This study also
      found an association between small bowel sarcomas and malignant melanoma in
      males, consistent with earlier studies, and an association between prostate
      cancer and malignant carcinoid tumors of the small bowel, a new observation. We
      conclude that adenocarcinomas of the small bowel may share risk factors with
      colorectal cancer.

PMID- 8268773
TI  - Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children.
AB  - The relative contribution of, and possible mechanism of interaction between,
      aflatoxin and hepatitis B virus (HBV) in the development of primary
      hepatocellular carcinoma can be better investigated now that markers of
      individual exposure to both factors are available. In this study, blood samples
      were collected over a 1-month period from 117 children aged 3 to 4 years,
      resident in Kuntair or Kerr Cherno in the Upper Niumi District of The Gambia.
      Samples were analyzed for aflatoxin-albumin (AF-alb) adducts, markers of HBV
      infection, liver enzymes [serum alanine aminotransferase (ALT)] as markers of
      liver damage, and glutathione S-transferase M1 genotype. All but two children
      showed detectable serum AF-alb with levels ranging from 2.2 to 250.4 pg aflatoxin
      B1-lysine equivalent/mg albumin. There was a significant positive correlation
      between AF-alb and ALT (r = 0.4; P < 0.001). HBV carriers showed moderately
      higher levels of AF-alb than noncarriers but the difference was not statistically
      significant and the association between AF-alb and ALT was unchanged when the HBV
      carriers were excluded from the analysis, suggesting that factors other than HBV
      infection contributed to the association. The null glutathione S-transferase M1
      genotype was infrequent (17.7%) in this population and was not associated with
      any difference in AF-alb adduct levels compared to glutathione S-transferase M1
      positive individuals. However, the percentage of individuals with the null
      genotype varied significantly between ethnic groups with 32.1% in Fula, 8.8% in
      Mandinka, and 13.3% in Wollof.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268774
TI  - In vivo nitrosoproline formation and other risk factors in Costa Rican children
      from high- and low-risk areas for gastric cancer.
AB  - The hypothesis that intragastric synthesis of N-nitroso compounds (NOC) in early
      life could play a role in gastric carcinogenesis was tested by applying the N
      nitrosoproline (NPRO) test to about 50 children living in high- and low-risk
      areas for stomach cancer in Costa Rica. The median values of excretion of NPRO
      and the sum of three nitrosamino acids (micrograms/12 h urine) were 10-20% of
      those in adults from other geographical high-risk areas for stomach cancer. The
      urinary NPRO level after proline intake was higher in children from the high-risk
      area (P < 0.04) and markedly reduced after ingestion of ascorbic acid together
      with proline (P < 0.05). NPRO levels on the day of proline intake were highly
      correlated with levels of nitrate excretion (P < 0.001). Mean levels of total NOC
      in an aqueous (pH 2) extract of cooked beans from the high- and low-risk areas
      were similar. Acid-catalyzed nitrosation of the extract increased the total NOC
      concentration up to 1000-fold, but there was no difference between samples from
      the two areas. About 10% of bean extracts from both areas showed weak direct
      acting genotoxicity in Escherichia coli; after acid-catalyzed nitrosation, all
      samples were genotoxic at similar levels. The diet of children in the low-risk
      area satisfied recommended levels of intake of energy and most nutrients except
      riboflavin and retinol equivalents. Diets from the high-risk area were deficient
      in energy intake and all nutrients except protein and vitamin C.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8268775
TI  - Ornithine decarboxylase activity in the mucosa of gastric remnant following
      gastric surgery.
AB  - Ornithine decarboxylase (ODC) activity and polyamine levels in mucosal specimens
      obtained by endoscopic biopsy from the stomal portion and greater curvature of
      the gastric remnant mucosa taken from 181 patients were determined and compared
      with the histopathological findings. The results obtained can be summarized as
      follows. (a) The ODC activity was significantly higher in the stomal portion [455
      +/- 340 (mean +/- SD)] of the gastric remnant than in the greater curvature (148
      +/- 107). The ODC activity of the stomal portion was significantly higher
      following a Billroth's II method (599 +/- 417) than following any other operative
      method that consists of a Billroth's I method (327 +/- 172) and a Roux-en Y (341
      +/- 191). (b) The levels of total polyamine, putrescine, spermidine, and spermine
      were also significantly higher in the stomal portion of the gastric remnant than
      in the greater curvature. There were no significant differences in the stomal
      tissue level of any of these substances among operative procedures used. (c)
      Histopathological changes consisting of glandular dilatation and an irregular
      glandular structure were detected more frequently in the stomal mucosal
      specimens, especially following a Billroth's II method. In summary, the present
      findings suggest that the measurement of ODC activity may thus be considered as
      one method of estimating the risk of carcinogenesis.

PMID- 8268776
TI  - Gross cystic disease fluid protein in nipple aspirates of breast fluid of Asian
      and non-Asian women.
AB  - Gross cystic disease fluid protein 15 (GCDFP-15) is universally present in the
      apocrine metaplastic epithelium of cystic breast disease and breast cancer, but
      it is rarely found in normal breast epithelium. Therefore GCDFP-15 detected in
      nipple aspirates of breast fluid (NAF) could serve as a biochemical marker of the
      presence and possibly extent of apocrine metaplasia within the breast. GCDFP-15
      levels were measured in NAF from 37 Asian and 78 non-Asian women using
      radioimmunoassay. GCDFP-15 (range, 0-81,643 micrograms/ml) was found in the NAF
      of all but 1 woman and was highly correlated between right and left breasts. Mean
      concentrations of GCDFP-15 were significantly lower in NAF from Asian compared
      with non-Asian women. Markedly reduced levels of GCDFP-15 were found in the 17
      women who had been parous in the previous 2 years. In women not parous within the
      prior 2 years, no relationship was found between GCDFP-15 levels and age, weight,
      age at menarche, first-degree family history of breast cancer, parity, oral
      contraceptive use, or smoking history. High concentrations of GCDFP-15 were found
      in the NAF of women with a history of a benign breast biopsy. Because similarly
      high levels of GCDFP-15 were found in NAF in over 40% of women without a history
      of benign breast biopsy, and because GCDFP-15 in the breast is produced only by
      apocrine metaplastic epithelium, we infer that the breasts of these women likely
      contain a significant degree of apocrine metaplasia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268777
TI  - 32P-postlabeling analysis of DNA adducts in human sperm cells from smokers and
      nonsmokers.
AB  - To determine the feasibility of using human sperm cells for DNA 32P-postlabeling
      analyses, and to evaluate the baseline level and the possible presence of smoking
      related DNA adducts in these cells, sperm DNA was isolated from specimens
      obtained from 12 heavy smokers, 12 light smokers, and 12 nonsmokers. Background
      levels of radioactivity were minimized by using magnet transfer of 32P-labeled
      mononucleotides to new polyethyleneimine cellulose plates. Compared with
      placental tissues, few adducts were observed. Diffuse radioactivity observed in
      some of the autoradiograms was minimally above background but the level of
      radioactivity expressed as putative adducts/nucleotide was not related to smoking
      status. It was not clear, in some cases, whether this radioactivity was
      associated with chemically bound adducts or was from nonspecifically bound
      chemicals, radiolabeled enzymes, or other proteins. One major discrete DNA adduct
      of unknown chemical structure was detected in three of the 36 samples analyzed
      (one nonsmoker and two smokers). Based on the level of radioactivity associated
      with various dilutions of a benzo(a)pyrene-derived adduct, our limit of
      sensitivity was at least 1.2 adducts/10(9) nucleotides. Our study emphasizes the
      need to more clearly define the significance of background radioactivity
      associated with DNA adduct maps where the measured adduct levels approximate
      detection limits defined by visual observance of adduct spots. This point is
      particularly relevant given that the 32P-postlabeling procedures rely, in part,
      on visual verification of the presence of DNA adducts.

PMID- 8268778
TI  - Nonrandom chromosomal abnormalities in lymphocyte cultures of individuals with
      colorectal polyps and of asymptomatic relatives of patients with colorectal
      cancer or polyps.
AB  - We studied chromosomal alterations in the peripheral blood lymphocytes of 10
      individuals with colorectal polyps and 10 asymptomatic first-degree relatives of
      patients with colon cancer or colorectal polyps. The analysis was performed on T
      lymphocytes using short term blood cultures and on B-lymphocytes by establishing
      lymphoblastoid cell lines by Epstein-Barr virus transformation. Chromosomal
      changes were not common in T- and B-lymphocytes. Chromosomes 1 and 5 were most
      frequently involved in numerical or structural changes in the patients with
      polyps as well as in the asymptomatic relatives. These alterations were observed
      in either the T-lymphocytes or the B-lymphocytes but rarely in both, thus
      accentuating the importance of studying both the cultures concurrently.
      Chromosome 5, which is known to play an important role in the development of
      adenomatous polyps, was found to be involved in 6 (60%) of 10 patients with
      polyps and 4 (40%) of 10 asymptomatic relatives. These findings show that
      lymphocytic chromosomal analysis can aid in identifying individuals who are
      genetically susceptible and are at a higher risk of developing colorectal cancer.
      Because lymphocytic chromosomal analysis is relatively simple and inexpensive, we
      expect that it will be very useful in screening asymptomatic individuals who are
      at a higher risk due to inherited or environmental factors.

PMID- 8268779
TI  - Changes in the patterns of initiation of cigarette smoking in the United States:
      1950, 1965, and 1980.
AB  - We examined changes in the patterns of the rates of smoking initiation in the
      United States by gender for 1950, 1965, and 1980. Data from National Health
      Interview Surveys on the ages people started smoking (survey years 1970, 1978,
      1979, 1980, 1987, and 1988) were used to construct age-specific rates of smoking
      initiation for males and females 10 to 24 years of age for 1950, 1965, and 1980.
      We used information from 87,483 white respondents who were between 20 and 50
      years of age when surveyed. In 1950, initiation was higher for males of all ages
      than for females, and smoking initiation rates were higher among those age 18
      years and older compared to those younger. Although still somewhat higher, the
      rates for males in 1965 had declined much more than those for females, and the
      tendency for higher rates in older youth was still evident. In 1980, no gender
      difference was seen and most initiation clearly took place in those younger than
      18 years of age. We concluded that the public health campaign has been successful
      in convincing older youth not to smoke. However, smoking initiation rates in
      younger adolescents have changed little, indicating that new approaches to
      tobacco control are necessary if smoking prevalence in the United States is to be
      further reduced.

PMID- 8268780
TI  - Exploring environmental barriers to participation in mammography screening in an
      HMO.
AB  - Despite an upward trend in mammography screening rates, rates among some
      demographic subgroups and rates of annual mammography remain low. Behavioral
      based interventions which move beyond invitational strategies to help women
      overcome their personal barriers may be necessary to increase participation. We
      developed a heuristic model based on the Health Belief Model and Social Learning
      Theory with the central hypothesis that the relative importance of environmental
      barriers in predicting screening behavior is a function of the woman's perceived
      risk, preventive orientation, and/or concerns about mammography. We completed
      telephone interviews with 313 women who did not obtain a mammogram and 350 women
      who had a mammogram within 365 days of an invitation from a Health Maintenance
      Organization-based breast cancer screening program. Results of multivariate
      analyses indicated that perceived risk did not mitigate the influence of logistic
      inconveniences associated with obtaining a mammogram. Preventive orientation as
      measured by smoking status interacted with belief that symptoms are a necessary
      prerequisite to a mammogram as a powerful predictor of participation; the
      greatest negative impact of concerns on participation was found among smokers. A
      similar relationship between concerns and participation, although only marginally
      significant, was observed among those who perceived it to be difficult to get to
      the screening center. Implications of the results for development of behavioral
      interventions and additional research are discussed.

PMID- 8268781
TI  - Methodologies for measuring carcinogen adducts in humans.
AB  - In summary, although some of the more optimistic aspirations for human
      biomonitoring studies envisaged a decade ago have not been realized thus far,
      some considerable advances have been made. The examples cited above indicate that
      the feasibility of biomonitoring has been clearly established. In addition, they
      demonstrate the need for preliminary biomarker testing and validation through
      transitional studies prior to their field application. In the next decade of
      research into carcinogen adducts in humans, continued improvements in the
      reproducibility and specificity of assays for DNA adducts will be needed. Perhaps
      the increasing use of hybrid methodologies to concentrate adducts followed by
      specific chemical analyses will allow such adducts to be monitored more
      precisely. Of course, further basic research into the mechanisms of
      carcinogenesis will allow the measurement of specific novel markers which are
      more closely tied to the disease endpoint than adducts. The development of new
      assays for determining metabolic phenotypes and genotypes relevant to
      carcinogenesis should improve our estimates of susceptibility (46-48). Such new
      approaches along with the sustained improvement of current assays will allow
      molecular approaches to continue to enrich cancer epidemiology in the future.

PMID- 8268782
TI  - Re: J. VanEenwyk et al., folate, vitamin C, and cervical intraepithelial
      neoplasia. Cancer Epidemiol., Biomarkers & Prev., 1: 119-124, 1992.

PMID- 8268783
TI  - Dealing with contamination: enzymatic control of carryover contamination in PCR.

PMID- 8268784
TI  - Setting up a PCR laboratory.

PMID- 8268785
TI  - Use of a sensitive fluorescent intercalating dye to detect PCR products of low
      copy number and high molecular weight.
AB  - The ability to routinely and specifically amplify and detect PCR products ranging
      in size from < 1 to > 10 kb, regardless of target template sequence or structure,
      would facilitate several tasks in human genome research. Generation of a wide
      size range of PCR products would potentially expedite isolation of uncloned DNA
      (gaps) represented in physical maps and provide a means for maintaining order and
      orientation of closely linked loci during analysis. Long-range PCR offers an
      alternative to isolation of genomic or cDNA clones from tissues or species where
      appropriate libraries are unavailable. This methodology also provides a powerful
      strategy to pursue directed transposon-based mapping and sequencing of templates
      of 100 kb or greater. Further development of basic PCR technology has been
      necessary in order to make it feasible to use large DNA targets as primary
      templates for genome analysis. Application of these extended PCR capacities would
      potentially save time, materials, and cost.

PMID- 8268786
TI  - Mistyping ACE heterozygotes.

PMID- 8268787
TI  - Use of chemical clamps in denaturing gradient gel electrophoresis: application in
      the detection of the most frequent Mediterranean beta-thalassemic mutations.

PMID- 8268788
TI  - Modified ASRA facilitates the characterization of activating point mutations in
      tumors, in which cancer cells constitute only a minor part of the investigated
      tissue.

PMID- 8268789
TI  - Search for improved electrophoretic conditions for PCR--single-strand
      conformation polymorphism analysis: is an SDS buffer condition useful.

PMID- 8268790
TI  - Degradation of DNA during the denaturation step of PCR.

PMID- 8268791
TI  - Amplifying DNA with arbitrary oligonucleotide primers.

PMID- 8268792
TI  - Determination of 5' ends of specific mRNAs by DNA ligase-dependent amplification.
AB  - We established a novel way to clone 5' ends of unknown length and sequence of
      individual cDNAs. T4 DNA ligase is employed to ligate an annealed duplex of
      complementary primers, one of them with a 4-nucleotide-long randomized overlap,
      to first-strand cDNA, generating a new 5' end. Subsequent PCR with a down-stream
      primer and a primer with specificity for this new 5' end leads to products that
      can easily be cloned and sequenced. Considerations for the choice of primers for
      ligation and amplification are given. We have used this method to determine the
      5' sequences of three independent mRNAs: the human collagen type-X gene, the
      chicken anchorin CII gene, and the human cytidine deaminase gene. We will discuss
      this method in comparison with other methods published for the amplification of
      unknown 5' ends of mRNA species.

PMID- 8268793
TI  - New insights into protein-tyrosine kinase receptor signaling complexes.

PMID- 8268794
TI  - Comparison of conformational characteristics in structurally similar protein
      pairs.
AB  - Although it is known that three-dimensional structure is well conserved during
      the evolutionary development of proteins, there have been few studies that
      consider other parameters apart from divergence of the main-chain coordinates. In
      this study, we align the structures of 90 pairs of homologous proteins having
      sequence identities ranging from 5 to 100%. Their structures are compared as a
      function of sequence identity, including not only consideration of C alpha
      coordinates but also accessibility, Ooi numbers, secondary structure, and side
      chain angles. We discuss how these properties change as the sequences become less
      similar. This will be of practical use in homology modeling, especially for
      modeling very distantly related or analogous proteins. We also consider how the
      average size and number of insertions and deletions vary as sequences diverge.
      This study presents further quantitative evidence that structure is remarkably
      well conserved in detail, as well as at the topological level, even when the
      sequences do not show similarity that is significant statistically.

PMID- 8268795
TI  - Resolution of the fluorescence equilibrium unfolding profile of trp aporepressor
      using single tryptophan mutants.
AB  - Single tryptophan mutants of the trp aporepressor, tryptophan 19-->phenylalanine
      (W19F) and tryptophan 99-->phenylalanine (W99F), were used in this study to
      resolve the individual steady-state and time-resolved fluorescence urea unfolding
      profiles of the two tryptophan residues in this highly intertwined, dimeric
      protein. The wild-type protein exhibits a large increase in fluorescence
      intensity and lifetime, as well as a large red shift in the steady-state
      fluorescence emission spectrum, upon unfolding by urea (Lane, A.N. & Jardetsky,
      O., 1987, Eur. J. Biochem. 164, 389-396; Gittelman, M.S. & Matthews, C.R., 1990,
      Biochemistry 29, 7011-7020; Fernando, T. & Royer, C.A., 1992, Biochemistry 31,
      6683-6691). Unfolding of the W19F mutant demonstrated that Trp 99 undergoes a
      large increase in intensity and a red shift upon exposure to solvent. Lifetime
      studies revealed that the contribution of the dominant 0.5-ns component of this
      tryptophan tends toward zero with increasing urea, whereas the longer lifetime
      components increase in importance. This lifting of the quenching of Trp 99 may be
      due to disruption of the interaction between the two subunits upon denaturation,
      which abolishes the interaction of Trp 99 on one subunit with the amide quenching
      group of Asn 32 on the other subunit (Royer, C.A., 1992, Biophys. J. 63, 741
      750). On the other hand, Trp 19 is quenched in response to unfolding in the W99F
      mutant. Exposure to solvent of Trp 19, which is buried at the hydrophobic dimer
      interface in the native protein, results in a large red shift of the average
      steady-state emission.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268796
TI  - Tryptophan replacements in the trp aporepressor from Escherichia coli: probing
      the equilibrium and kinetic folding models.
AB  - Mutants of the dimeric Escherichia coli trp aporepressor are constructed by
      replacement of the two tryptophan residues in each subunit in order to assess the
      effects on equilibrium and kinetic fluorescence properties of the folding
      reaction. The three kinetic phases detected by intrinsic tryptophan fluorescence
      in refolding of the wild-type aporepressor are also observed in folding of both
      Trp 19 to Phe and Trp 99 to Phe single mutants, demonstrating that these phases
      correspond to global rather than local conformational changes. Comparison of
      equilibrium fluorescence (Royer, C.A., Mann, C.J., & Matthews, C.R., 1993,
      Protein Sci. 2, 1844-1852) and circular dichroism transition curves induced by
      urea shows that replacement of either Trp 19 or Trp 99 results in noncoincident
      behavior. Unlike the wild-type protein (Gittelman, M.S. & Matthews, C.R., 1990,
      Biochemistry 29, 7011-7020), tertiary and/or quaternary structures are disrupted
      at lower denaturant concentration than is secondary structure. The equilibrium
      results can be interpreted in terms of enhancement in the population of a
      monomeric folding intermediate in which the lone tryptophan residue is highly
      exposed to solvent, but in which substantial secondary structure is retained. The
      location of both mutations at the interface between the two subunits (Zhang,
      R.G., et al., 1987, Nature 327, 591-597) provides a simple explanation for this
      phenomenon.

PMID- 8268797
TI  - Kinetics of folding and association of differently glycosylated variants of
      invertase from Saccharomyces cerevisiae.
AB  - A core-glycosylated form of the dimeric enzyme invertase has been isolated from
      secretion mutants of Saccharomyces cerevisiae blocked in transport to the Golgi
      apparatus. This glycosylation variant corresponds to the form that folds and
      associates during biosynthesis of the protein in vivo. In the present work, its
      largely homogeneous subunit size and well-defined quaternary structure were
      utilized to characterize the folding and association pathway of this highly
      glycosylated protein in comparison with the nonglycosylated cytoplasmic and the
      high-mannose-glycosylated periplasmic forms of the same enzyme encoded by the
      suc2 gene. Renaturation of core-glycosylated invertase upon dilution from
      guanidinium-chloride solutions follows a unibimolecular reaction scheme with
      consecutive first-order subunit folding and second-order association reactions.
      The rate constant of the rate-limiting step of subunit folding, as detected by
      fluorescence increase, is k1 = 1.6 +/- 0.4 x 10(-3) s-1 at 20 degrees C; it is
      characterized by an activation enthalpy of delta H++ = 65 kJ/mol. The reaction is
      not catalyzed by peptidyl-prolyl cis-trans isomerase of the cyclophilin type.
      Reactivation of the enzyme depends on protein concentration and coincides with
      subunit association, as monitored by size-exclusion high-pressure liquid
      chromatography. The association rate constant, estimated by numerical simulation
      of reactivation kinetics, increases from 5 x 10(3) M-1 s-1 to 7 x 10(4) M-1 s-1
      between 5 and 30 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268798
TI  - Mechanism of phage P22 tailspike protein folding mutations.
AB  - Temperature-sensitive folding (tsf) and global-tsf-suppressor (su) point
      mutations affect the folding yields of the trimeric, thermostable phage P22
      tailspike endorhamnosidase at elevated temperature, both in vivo and in vitro,
      but they have little effect on function and stability of the native folded
      protein. To delineate the mechanism by which these mutations modify the
      partitioning between productive folding and off-pathway aggregation, the kinetics
      of refolding after dilution from acid-urea solutions and the thermal stability of
      folding intermediates were analyzed. The study included five tsf mutations of
      varying severity, the two known su mutations, and four tsf/su double mutants. At
      low temperature (10 degrees C), subunit-folding rates, measured as an increase in
      fluorescence, were similar for wild-type and mutants. At 25 degrees C, however,
      tsf mutations reduced the rate of subunit folding. The su mutations increased
      this rate, when present in the tsf-mutant background, but had no effect in the
      wild-type background. Conversely, tsf mutations accelerated, and su mutations
      retarded the irreversible off-pathway reaction, as revealed by temperature down
      shifts after varied times during refolding at high temperature (40 degrees C).
      The kinetic results are consistent with tsf mutations destabilizing and su
      mutations stabilizing an essential subunit folding intermediate. In accordance
      with this interpretation, tsf mutations decreased, and su mutations increased the
      temperature resistance of folding intermediates, as disclosed by temperature up
      shifts during refolding at 25 degrees C. The stabilizing and destabilizing
      effects were most pronounced early during refolding. However, they were not
      limited to subunit-folding intermediates and were also observable during thermal
      unfolding of the native protein.

PMID- 8268799
TI  - Macromolecular solvation energies derived from small molecule crystal morphology.
AB  - The morphology of small molecule crystals provides a model for evaluating surface
      solvation energies in a system with similar packing density to that observed for
      amino acid residues in proteins. The solvation energies associated with the
      transfer of methylene and carboxyl groups between vacuum and aqueous phases are
      estimated to be approx. $40 and -260 cal/A2, respectively, from an analysis of
      the morphology of succinic acid crystals. These solvation energies predict values
      for contact angles in reasonable agreement with measurements determined from
      macroscopic monolayer surfaces. Transfer free energies between vapor and water
      phases for a series of carboxylic acids are also predicted reasonably well by
      these solvation energies, provided the surface exposure of different groups is
      quantitated with the molecular surface area rather than the more traditional
      accessible surface area. In general, molecular surfaces and molecular surface
      areas are seen to have important advantages for characterizing the structure and
      energetics of macromolecular surfaces. Crystal faces of succinic acid with the
      lowest surface energies in aqueous solution are characteristically smooth.
      Increasing surface roughness and apolarity are associated with higher surface
      energies, which suggests an approach for modifying the surface properties of
      proteins and other macromolecules.

PMID- 8268800
TI  - Aldehyde dehydrogenases: widespread structural and functional diversity within a
      shared framework.
AB  - Sequences of 16 NAD and/or NADP-linked aldehyde oxidoreductases are aligned,
      including representative examples of all aldehyde dehydrogenase forms with wide
      substrate preferences as well as additional types with distinct specificities for
      certain metabolic aldehyde intermediates, particularly semialdehydes, yielding
      pairwise identities from 15 to 83%. Eleven of 23 invariant residues are glycine
      and three are proline, indicating evolutionary restraint against alteration of
      peptide chain-bending points. Additionally, another 66 positions show high
      conservation of residue type, mostly hydrophobic residues. Ten of these occur in
      predicted beta-strands, suggesting important interior-packing interactions. A
      single invariant cysteine residue is found, further supporting its catalytic
      role. A previously identified essential glutamic acid residue is conserved in all
      but methyl malonyl semialdehyde dehydrogenase, which may relate to formation by
      that enzyme of a CoA ester as a product rather than a free carboxylate species.
      Earlier, similarity to a GXGXXG segment expected in the NAD-binding site was
      noted from alignments with fewer sequences. The same region continues to be
      indicated, although now only the first glycine residue is strictly conserved and
      the second (usually threonine) is not present at all, suggesting greater variance
      in coenzyme-binding interactions.

PMID- 8268802
TI  - A peptide analog of the calmodulin-binding domain of myosin light chain kinase
      adopts an alpha-helical structure in aqueous trifluoroethanol.
AB  - A 22-residue synthetic peptide encompassing the calmodulin (CaM)-binding domain
      of skeletal muscle myosin light chain kinase was studied by two-dimensional NMR
      and CD spectroscopy. In water the peptide does not form any regular structure;
      however, addition of the helix-inducing solvent trifluoroethanol (TFE) causes it
      to form an alpha-helical structure. The proton NMR spectra of this peptide in 25%
      and 40% TFE were assigned by double quantum-filtered J-correlated spectroscopy,
      total correlation spectroscopy, and nuclear Overhauser effect correlated
      spectroscopy spectra. In addition, the alpha-carbon chemical shifts were obtained
      from (1H,13C)-heteronuclear multiple quantum coherence spectra. The presence of
      numerous dNN(i, i + 1), d alpha N(i, i + 3), and d alpha beta(i, i + 3) NOE
      crosspeaks indicates that an alpha-helix can be formed from residues 3 to 20;
      this is further supported by the CD data. Upfield alpha-proton and downfield
      alpha-carbon shifts in this region of the peptide provide further support for the
      formation of an alpha-helix. The helix induced by TFE appears to be similar to
      that formed upon binding of the peptide to CaM.

PMID- 8268801
TI  - Import of cytochrome b2 to the mitochondrial intermembrane space: the tightly
      folded heme-binding domain makes import dependent upon matrix ATP.
AB  - Cytochrome b2 is synthesized as a precursor in the cytoplasm and imported to the
      intermembrane space of yeast mitochondria. We show here that the precursor
      contains a tightly folded heme-binding domain and that translocation of this
      domain across the outer membrane requires ATP. Surprisingly, it is ATP in the
      mitochondrial matrix rather than external ATP that drives import of the heme
      binding domain. When the folded structure of the heme-binding domain is disrupted
      by mutation or by urea denaturation, import and correct processing take place in
      ATP-depleted mitochondria. These results indicate that (1) cytochrome b2 reaches
      the intermembrane space without completely crossing the inner membrane, and (2)
      some precursors fold outside the mitochondria but remain translocation-competent,
      and import of these precursors in vitro does not require ATP-dependent cytosolic
      chaperone proteins.

PMID- 8268803
TI  - A 19F-NMR study of the membrane-binding region of D-lactate dehydrogenase of
      Escherichia coli.
AB  - D-Lactate dehydrogenase (D-LDH) is a membrane-associated respiratory enzyme of
      Escherichia coli. The protein is composed of 571 amino acid residues with a
      flavin adenine dinucleotide (FAD) cofactor, has a molecular weight of
      approximately 65,000, and requires lipids or detergents for full activity. We
      used NMR spectroscopy to investigate the structure of D-LDH and its interaction
      with phospholipids. We incorporated 5-fluorotryptophan (5F-Trp) into the native
      enzyme, which contains five tryptophan residues, and into mutant enzymes, where a
      sixth tryptophan is substituted into a specific site by oligonucleotide-directed
      mutagenesis, and studied the 5F-Trp-labeled enzymes using 19F-NMR spectroscopy.
      In this way, information was obtained about the local environment at each native
      and substituted tryptophan site. Using a nitroxide spin-labeled fatty acid, which
      broadens the resonance from any residue within 15 A, we have established that the
      membrane-binding area of the protein includes the region between Tyr 228 and Phe
      369, but is not continuous within this region. This conclusion is strengthened by
      the results of 19F-NMR spectroscopy of wild-type enzyme labeled with
      fluorotyrosine or fluorophenylalanine in the presence and absence of a nitroxide
      spin-labeled fatty acid. These experiments indicate that 9-10 Phe and 3-4 Tyr
      residues are located near the lipid phase.

PMID- 8268804
TI  - Isolation and characterization of a resistant core peptide of recombinant human
      granulocyte-macrophage colony-stimulating factor (GM-CSF); confirmation of the GM
      CSF amino acid sequence by mass spectrometry.
AB  - A trypsin-resistant core peptide of recombinant human granulocyte-macrophage
      colony-stimulating factor (rhGM-CSF) was isolated and analyzed by high-energy Cs+
      liquid secondary-ion (LSI) mass spectrometric analysis. This analysis provided
      successful detection of the high-mass disulfide-linked core peptide as well as
      information confirming the existence of disulfide pairing. Similarly, LSI mass
      spectrometric analysis of the peptide fragments isolated chromatographically from
      a Staphylococcus aureus V8 protease digest of rhGM-CSF provided rapid
      confirmation of the cDNA-derived sequence and determination of the existing
      disulfide bonds between cysteine residues 54-96 and 88-121. Electrospray
      ionization mass spectrometry was employed to measure the molecular weight of the
      intact protein and to determine the number of the disulfide bonds in the protein
      molecule by comparative analysis of the protein before and after reduction with
      beta-mercaptoethanol.

PMID- 8268805
TI  - Heme biosynthesis in mammalian systems: evidence of a Schiff base linkage between
      the pyridoxal 5'-phosphate cofactor and a lysine residue in 5-aminolevulinate
      synthase.
AB  - 5-Aminolevulinate synthase is the first enzyme of the heme biosynthetic pathway
      in nonplant higher eukaryotes. Murine erythroid 5-aminolevulinate synthase has
      been purified to homogeneity from an Escherichia coli overproducing strain, and
      the catalytic and spectroscopic properties of this recombinant enzyme were
      compared with those from nonrecombinant sources (Ferreira, G.C. & Dailey, H.A.,
      1993, J. Biol. Chem. 268, 584-590). 5-Aminolevulinate synthase is a pyridoxal 5'
      phosphate-dependent enzyme and is functional as a homodimer. The recombinant 5
      aminolevulinate synthase holoenzyme was reduced with tritiated sodium borohydride
      and digested with trypsin. A single peptide contained the majority of the label.
      The tritiated peptide was isolated, and its amino acid sequence was determined;
      it corresponded to 15 amino acids around lysine 313, to which pyridoxal 5'
      phosphate is bound. Significantly, the pyridoxyllysine peptide is conserved in
      all known cDNA-derived 5-aminolevulinate synthase sequences and is present in the
      C-terminal (catalytic) domain. Mutagenesis of the 5-aminolevulinate synthase
      residue, which is involved in the Schiff base linkage with pyridoxal 5'
      phosphate, from lysine to alanine or histidine abolished enzyme activity in the
      expressed protein.

PMID- 8268806
TI  - Amide proton exchange rates of oxidized and reduced Saccharomyces cerevisiae iso
      1-cytochrome c.
AB  - Proton NMR spectroscopy was used to determine the rate constant, kobs, for
      exchange of labile protons in both oxidized (Fe(III)) and reduced (Fe(II)) iso-1
      cytochrome c. We find that slowly exchanging backbone amide protons tend to lack
      solvent-accessible surface area, possess backbone hydrogen bonds, and are present
      in regions of regular secondary structure as well as in omega-loops. Furthermore,
      there is no correlation between kobs and the distance from a backbone amide
      nitrogen to the nearest solvent-accessible atom. These observations are
      consistent with the local unfolding model. Comparisons of the free energy change
      for denaturation, delta Gd, at 298 K to the free energy change for local
      unfolding, delta Gop, at 298 K for the oxidized protein suggest that certain
      conformations possessing higher free energy than the denatured state are detected
      at equilibrium. Reduction of the protein results in a general increase in delta
      Gop. Comparisons of delta Gd to delta Gop for the reduced protein show that the
      most open states of the reduced protein possess more structure than its
      chemically denatured form. This persistent structure in high-energy conformations
      of the reduced form appears to involve the axially coordinated heme.

PMID- 8268807
TI  - Application of molecular dynamics and free energy perturbation methods to
      metalloporphyrin-ligand systems II: CO and dioxygen binding to myoglobin.
AB  - The protein contribution to the relative binding affinity of the ligands CO and
      O2 toward myoglobin (Mb) has been simulated using free energy perturbation
      calculations. The tautomers of the His E7 residue are different for the
      oxymyoglobin (MbO2) and carboxymyoglobin (MbCO) systems. This was modeled by
      performing two-step calculations that mutate the ligand and mutate the His E7
      tautomers in separate steps. Differences in hydrogen bonding to the O2 and CO
      ligands were incorporated into the model. The O2 complex was calculated to be 2-3
      kcal/mol more stable than the corresponding CO complex when compared to the same
      difference in an isolated heme control. This value agrees well with the
      experimental value of 2.0 kcal/mol. In qualitative agreement with experiments,
      the Fe-C-O bond is found to be bent (theta = 159.8 degrees) with a small tilt
      (theta = 6.2 degrees). The contributions made by each of the 29 residues--within
      the 9.0-A radius of the iron atom--to the free energy difference are separated
      into van der Waals and electrostatic contributions; the latter contributions are
      dominant. Aside from the proximal histidine and the heme group, the residues
      having the largest difference in free energy in mutating MbO2-->MbCO are His E7,
      Phe CD1, Phe CD4, Val E11, and Thr E10.

PMID- 8268808
TI  - Substrate recognition by the vitamin K-dependent gamma-glutamyl carboxylase:
      identification of a sequence homology between the carboxylase and the carboxylase
      recognition site in the substrate.

PMID- 8268809
TI  - Structural argument for N-terminal initiation of protein folding.

PMID- 8268810
TI  - Solvent water and protein behavior: view through a retroscope.

PMID- 8268811
TI  - [Dispersing ability of human blood plasma in the normal state and in various
      types of ischemic heart disease].

PMID- 8268812
TI  - [Recombinant equine Venezuelan encephalomyelitis virus, expressing HBsAg].

PMID- 8268813
TI  - [The systematic position of the holocene population of the mammoth, Mammuthus
      primigenius (Blumenbach, 1799), of the Vrangel Island (Northeast Siberia)].

PMID- 8268814
TI  - [Functional activity of the abdominal gland and marking behavior of Mongolian
      gerbils (Meriones unguiculatus)].

PMID- 8268815
TI  - Immunological specificity as metaphor.

PMID- 8268816
TI  - Is hysteresis of yeast hexokinase A due to isomerization or dissociation of the
      enzyme molecule?

PMID- 8268817
TI  - Participation of glycosylation sites in the binding of Staphylococcus aureus to
      laminin.
AB  - 1. Microbial pathogenicity is in many instances associated with the ability to
      adhere to host surfaces or to extracellular matrix components. 2. Laminin is a
      major glycoprotein of basement membranes which can promote specific bacterial
      adhesion. Staphylococcus aureus is a pathogenic bacterium which presents a
      laminin receptor of about 50-kDa molecular mass (Lopes JD, Reis M & Brentani RR
      (1985). Science, 229: 275-277). 3. Adhesion inhibition assays of [125iodine]
      labeled bacteria to laminin demonstrate that the receptor binding site is
      contained in the pepsin-derived (P1) laminin fragment. 4. Cell adhesion to
      laminin is unaffected by periodate oxidation of sugars on the surface of bacteria
      or by removal of divalent cations by ethylenediaminetetraacetic acid (EDTA). In
      contrast, bacterial adhesion is reduced when laminin is deglycosylated with N
      glycosidase F or when bacteria are submitted to controlled trypsin digestion. 5.
      Laminin binding to the S. aureus 50-kDa band in immunoblotting assays has
      confirmed all of these results obtained in cell adhesion experiments.

PMID- 8268818
TI  - Comparison of the urease test and of direct smear examination in the control of
      treatment of Helicobacter pylori-induced infection.
AB  - The sensitivity and specificity of the preformed urease test and of carbolfuchsin
      stained smears for the diagnosis of the presence of Helicobacter pylori in
      gastric mucosa were evaluated before and after antimicrobial treatment. The
      results obtained by culture were used as the reference point. We studied 41
      patients with endoscopically diagnosed duodenal ulcer. Twenty-five of these were
      treated with furazolidone (100 mg t.i.d.), amoxicillin (500 mg t.i.d.) and
      metronidazole (250 mg t.i.d.) for 5 days and then with only furazolidone (100 mg
      t.i.d.) for an additional 25 days. The 16 control patients were treated with
      cimetidine (800 mg, 4 times a day). The sensitivity of the urease test and of
      direct smear examination was 100% before treatment and 84.6% and 92.3%,
      respectively, after treatment. We conclude that the urease test and carbolfuchsin
      stained smears, which are highly sensitive for H. pylori diagnosis, present
      reduced sensitivity when they are employed for the follow-up of patients treated
      with antimicrobials.

PMID- 8268819
TI  - Echovirus type 19 and herpes simplex type 2 infection in human placenta tissue
      explants.
AB  - 1. Light and electron microscopy have been used to characterize echovirus 19 and
      herpes simplex type 2 infection of human placenta tissue in vitro.
      Immunofluorescence, autoradiography and virus adsorption were used to determine
      virus replication in this system. 2. Placental tissue was permissive to echovirus
      19. Trophoblast cells were lysed with liberation of mature virions. However,
      during the 48-h period of observation, few cells were damaged and the
      trophoblastic structure was maintained. 3. HSV-2 infection in placental tissue
      was aborted although trophoblastic cells allowed virus adsorption, penetration
      and uncoating. A characteristic cytopathic effect was observed in infected
      trophoblastic cells in spite of the abortive infection.

PMID- 8268820
TI  - Decrease in passive cutaneous anaphylaxis reactions in rats secondary to stress.
AB  - Anaphylaxis was assayed by the passive cutaneous anaphylaxis (PCA) test in male
      Wistar rats (250 g body weight). Three experimental groups were used: animals
      restrained in an electric chamber and submitted to electric shock immediately
      after sensitization and 24 h before anaphylaxis (31 animals), animals restrained
      in the electric chamber for the same time but receiving no electric shock (23
      animals), and non-manipulated, home-cage control animals (24 animals). The
      frequency of PCA reactions was decreased in the group of animals submitted to
      restraint when compared with the home-cage control group. However, the group of
      animals submitted to both restraint and electric shock showed no decrease in the
      frequency of PCA reactions. It is suggested that, in rats, stress induced by
      restraint decreases PCA reactions and that this decrease is counteracted by a
      simultaneous stress induced by electric shock.

PMID- 8268821
TI  - Systemic immunization of mature mice by the oral route.
AB  - 1. Mice of several strains which are susceptible to the induction of oral
      tolerance by a single gavage with 20 mg of ovalbumin (Ova) when young adults (7-8
      weeks old) become less susceptible or refractory to tolerance induction when
      mature (20-40 weeks old). The antibody-forming capacity of these mature animals
      remains invariant compared to young adults (8-10 weeks old). 2. Mature mice of
      several strains display significant serum antibody responses to 3 gavages (days
      0, 7 and 28) with Ova; as assessed by ELISA titers, these responses are similar
      in magnitude to those elicited by standard ip immunization with small doses of
      Ova. 3. In mature H-III mice, gavages on days 0, 7 and 28 induced significant
      antibody formation. On the contrary, the ingestion of the same amounts of Ova on
      days 0, 7 and 28 induced oral tolerance. Concomitant gavage with saline on the
      days of Ova ingestion failed to inhibit tolerance induction. 4. In H-III mice
      displaying circulating antibodies induced by repeated gavage with Ova, additional
      ip injections of Ova failed to increase the antibody titers.

PMID- 8268822
TI  - Cytomegalovirus, human herpesvirus 6 and human T cell leukemia virus infection in
      renal transplanted patients in the northeast of Brazil.
AB  - The seroprevalence of antibodies against cytomegalovirus (CMV), human herpesvirus
      6 (HHV-6) and human T cell leukemia virus type 1 (HTLV-1), determined by ELISA
      and by fluorescence in 54 renal transplanted patients, was 96.2%, 88.8% and
      11.1%, respectively. These values are relatively high when compared with the
      results obtained for healthy individuals of the same age groups from Recife,
      Northeastern Brazil. Active CMV infection was detected by the presence of IgM
      antibodies and/or virus isolation in 13 (24%) patients. Kidney rejection and
      renal dysfunction were observed in 11 of these 13 patients, whereas 3 of 6 HTLV-1
      antibody-positive individuals presented these complications. All HTLV-1 positive
      patients were also positive to IgG CMV and HHV-6 antibodies. The importance of
      the three viruses in this clinical condition is suggested by the high
      seropositivity rates compared with the healthy population. The group may also
      represent a potential source of HTLV-1 infection in this non-endemic area.

PMID- 8268823
TI  - Neonatal treatment with naloxone causes permanent hyperalgesia in rats.
AB  - The effect of treatment with naloxone early in life on pain responsiveness was
      studied in Wistar rats. Litters of six rats were divided equally into groups of 3
      pups receiving daily naloxone (50 mg/kg, sc) and 3 pups receiving saline from the
      3rd to 18th day of life. On days 30, 50, 70 and 90, one group of animals
      previously injected during suckling with naloxone (N = 21) and another with
      saline (N = 21) were submitted to the hot-plate test to measure the latency to
      paw licking. Other groups of rats also treated during suckling with naloxone (N =
      13) and saline (N = 14) were assessed for the antinociceptive effect of morphine
      (10 mg/kg,sc). The naloxone group displayed a lower latency than the saline group
      in all test sessions and a diminished analgesic response to morphine. The results
      indicate that the use of naloxone (an antagonist opioid) during suckling, the
      brain growth spurt period, facilitates a long-lasting increased pain
      responsiveness and alters antialgesic mechanisms. In this respect, the opioid and
      non-opioid effects of naloxone on the ontogeny of neural systems should be taken
      into account.

PMID- 8268824
TI  - Measurement of plasma verapamil levels by high-performance liquid chromatography.
AB  - 1. We have developed an alternative procedure for the measurement of verapamil
      levels in human plasma by reverse-phase high performance liquid chromatography
      with fluorimetric detection. 2. Prior to assay, plasma is submitted to a double
      extraction procedure, using first n-heptane in alkaline medium and then an acid
      phosphate buffer. Flecainide, a compound not related to verapamil, is used as
      internal standard. Mean recoveries of 70 and 63% were obtained for verapamil and
      flecainide, respectively. 3. The sensitivity (5 ng/ml), reproducibility (inter
      assay %CV = 1.7-8.7; intra-assay %CV = 2-4) and high recovery during sample clean
      up make this method useful for the quantitation of verapamil in therapeutic
      monitoring and pharmacokinetic studies. 4. The method is illustrated with the
      pharmacokinetic results obtained for 14 healthy male volunteers who received a
      single 240 mg dose of the commercially available tablets of Dilacoron Retard 240
      mg. The mean values for the area under the curve from 0 to 24 h (AUC[0-24]),
      maximum achieved concentration (Cmax) and time to achieve the maximum
      concentration (Tmax) were 863 ng h-1 ml-1, 112 ng/ml and 4 h, respectively.

PMID- 8268825
TI  - Effect of bilateral nephrectomy on hypertension produced by acute aortic
      coarctation.
AB  - 1. The hemodynamic responses to acute (45 min) aortic coarctation were studied in
      conscious intact (N = 7) or bilaterally nephrectomized (N = 7) Wistar rats (250
      320 g). The degree of constriction of the aorta was monitored by reducing aortic
      flow (measured with a pulsed Doppler flowmeter) to 40% of the basal level. 2. The
      nephrectomized rats presented a smaller (P < 0.05) increase in carotid pressure
      (14-17%) than the intact rats (25-36%). Although the aortic constriction reduced
      significantly the aortic flow to 40% of the basal level in both groups of rats,
      the calculated change in aortic resistance imposed by coarctation in the intact
      group was significantly (P < 0.05) higher (167-292%) than that observed (173
      183%) in the nephrectomized group, except 5 min after coarctation. 3. The
      hemodynamic data obtained in the present study confirm our findings that
      nephrectomized rats display a blunted hypertensive response to acute aortic
      coarctation which is attributed mainly to the mechanical effect of constriction.
      In addition, the present data indicate that the release of vasopressor substances
      triggered by the kidneys in intact subjects are responsible for the gradual
      increase in aortic resistance during coarctation.

PMID- 8268826
TI  - Effect of bafilomycin on proximal bicarbonate absorption in the rat.
AB  - To evaluate the relative importance of the V-type H(+)-ATPase in proximal
      bicarbonate reabsorption in vivo, proximal tubules of male and female Wistar rats
      (180 to 260 g) were perfused with bicarbonate-Ringer solution with and without
      the addition of 2 microM bafilomycin A1. Bafilomycin significantly increased
      stationary pH from 6.75 +/- 0.05 (N = 39) to 6.86 +/- 0.03 (N = 82), the
      stationary concentration of bicarbonate from 5.24 +/- 0.62 to 6.33 +/- 0.46 mM
      and the half-time of acidification from 3.72 +/- 0.22 to 4.65 +/- 0.25 s, and
      significantly decreased net bicarbonate reabsorption from 3.17 +/- 0.21 to 2.55
      +/- 0.15 nmol s-1 cm-2, that is, by 20%. Since bafilomycin is considered to be a
      specific inhibitor for V-type H(+)-ATPase, these data establish 1) the existence
      of this type of transport in the rat proximal tubule and 2) that approximately a
      fifth of the total proximal bicarbonate reabsorption is due to this mechanism of
      transport.

PMID- 8268827
TI  - Transepithelial pH gradients in cortical distal tubules during metabolic
      alkalosis.
AB  - 1. The cortical distal tubule of the rat kidney participates in the regulation of
      acid-base balance, showing bicarbonate reabsorption, secretion or absence of
      transport under different experimental conditions. In the present study, we
      measured differences in transepithelial pH using double ion-exchange
      resin/reference microelectrodes in control and alkalotic (chronic plus acute)
      male Wistar rats and in alkalotic rats receiving a K+ supplement in diet and
      infusion. 2. pH was measured in the tubule lumen during stationary microperfusion
      with 25 mM bicarbonate Ringer solution, and in peritubular vessels next to the
      perfused tubules. 3. Differences in transepithelial pH were 0.70 +/- 0.12 (N =
      16) pH units in early distal tubules (ED) and 1.03 +/- 0.050 (N = 15) in late
      distal tubules LD) of control rats, 0.22 +/- 0.056 (N = 17) in ED and 0.25 +/-
      0.050 (N = 20) in LD of alkalotic rats, and -0.02 +/- 0.039 (N = 24) in ED and 
      0.02 +/- 0.040 (N = 24) in LD of K(+)-supplemented alkalotic rats. 4. In control
      rats, the transepithelial potential difference (PD) (-8.9 +/- 1.45 mV (N = 16) in
      ED and -32.7 +/- 2.99 mV (N = 15) in LD) was not large enough to explain
      transepithelial H+ and HCO3- gradients, suggesting the presence of an active
      transport mechanism responsible for their maintenance. 5. The present data show
      that the cortical distal tubule is able to establish transepithelial pH (HCO3-)
      differences, that these differences are reduced by alkalosis and abolished by
      alkalosis plus K+ supplementation, and that, although inversion of pH gradients
      (evidence for bicarbonate secretion) was observed in individual tubules, this
      inversion was not significant in the groups studied.

PMID- 8268828
TI  - On the significance of chemiluminescence induced by the blood polymorphonuclear
      leukocytes. I. Normal values.
AB  - In spite of the fact that chemiluminescence (CL) produced by the in vitro
      stimulated polymorphonuclear leukocytes is now a current method for the
      quantitative measurement of phagocytosis, its clinical use is still limited due
      to some controversies mostly technical. By comparing the different forms of
      presentation of the results, we proposed as stimulation index, the ratio of CL in
      the stimulated sample to that in the nonstimulated as measured at the same time
      interval and in the same number of cells (1 x 10(6)/ml). Measurements performed
      in a group of 200 healthy individuals, aged 20-70 years, with various occupations
      showed wide large variations of both the stimulation index of 23.5 +/- 12.3 and
      in a lesser degree of the CL kinetics. We suggest different possibilities of
      interpretation of the results obtained by this method (both the stimulated index
      and the CL kinetics) in order to obtain maximum information concerning the
      cellular immunity for clinical use.

PMID- 8268829
TI  - Serum markers of collagen metabolism in patients with diseases of the respiratory
      system.
AB  - The variations of the serum markers of collagen metabolism such as total and free
      hydroxyproline and hydroxylysine and collagen-like protein were studied in
      patients with chronic bronchitis, pneumonia and emphysema as compared to healthy
      controls. The values found in diseased subjects were significantly higher than in
      controls.

PMID- 8268830
TI  - The zinc-immunodeficiency relationship in old patients.
AB  - The influence of oral zinc sulphate therapy on the humoral immunity was
      investigated by dosages of serum immunoglobulins (Ig) and of plasma zinc levels
      in 12 patients with a mean age of 70 years, in comparison with other 11 patients
      treated with placebo and with a control group of 50 apparently healthy subjects.
      The results of this double-blind study demonstrated the zinc effect on the
      immunoregulation, as the Ig levels, and particularly those of the IgG class,
      initially high, were lowered in a statistically significant proportion. It is
      assumed that further clinical trials with various zinc concentrations could bring
      more information on this trace element participation in the humoral
      immunoregulation.

PMID- 8268831
TI  - Changes of serum complement and of circulating immune complexes in patients with
      multiple sclerosis.
AB  - The changes of total hemolytic complement (CH50), of C3 and C1q components and of
      the circulating immune complexes (CIC) were studied in a group of 112 patients
      with multiple sclerosis (MS) and in 50 controls. The attack was taken as a basis
      of observation. It was observed that in MS attacks CH50, C3 and C1q were
      decreased owing to the activation of the complement in the classical way. The
      CH50 values were found well enough correlated with C3 and C1q (r = 0.535) and
      respectively r = 0.497) and clearly correlated with the CIC values (r = 0.907). A
      sharp decrease of CH50 increases the probability of the appearance of an attack
      with slow remission and the probability of an attack with slow remission is the
      greater, the greater the increase of CIC values. Low CH50, C3 and C1q values
      correlated with high CIC values may be considered markers of severity in MS.

PMID- 8268832
TI  - [The diagnostic difficulties in a case of primary systemic amyloidosis].

PMID- 8268833
TI  - The therapeutic action of cyclosporin A (Sandimmun): its application in
      rheumatoid arthritis.
AB  - The main properties, mechanism of action, mode of administration, side effects
      and therapeutic indications of Cyclosporin A are reviewed, with special emphasis
      on its applications in rheumatoid arthritis (RA). The drug administration in
      small doses, only in patients with severe RA, refractory to the usual
      antirheumatic therapy, was effective in a significant proportion of cases.

PMID- 8268834
TI  - Ventricular late potentials. Part I. Techniques, detection, interpretation.
AB  - The first part of this review on the ventricular late potentials (VLP) presents
      the actual methods of diagnosis by: 1. Analysis in the time domain (ATD),
      currently used in most of the studies on the VLP. 2. Analysis in the frequency
      domain (AFD), in course of study, in which the author has a personal experience
      and has drawn criteria for the VLP diagnosis. 3. Beat-by-beat analysis, also in a
      stage of study. Irrespective of the analysis type, the criteria of positivity for
      VLP presence and the techniques of recording are analysed and commented according
      to the author's own experience. The interpretation of these techniques and their
      application in clinical practice shall make the object of the second part of this
      review.

PMID- 8268835
TI  - Comparison of risks in cardiovascular diseases.
AB  - The paper presents the estimations of the short-time and the long-time (10 years)
      risks of developing a cardiovascular disease (CD). The standard risk factors
      considered were: age, deviation from the ideal weight, number of cigarettes
      smoked per day, level of serum cholesterol and systolic blood pressure. The
      cardiovascular diseases likely to be induced by these risk factors were:
      myocardial infarction, angina pectoris, ischemic heart diseases and stroke. The
      comparison of the estimated probabilities of developing the disease for various
      risk factors profiles emphasizes the value of epidemiologic intervention already
      in young agers.

PMID- 8268836
TI  - Hypothesis of transition in two ways from atrial fibrillation to sinus rhythm.
AB  - A hypothesis of transition from atrial fibrillation to sinus rhythm in close
      relation with monophasic action potential duration is proposed. The first way:
      the prolongation of the right atrial refractoriness reduces the wave fronts below
      a critical number and their collision terminates the arrhythmia. The second way:
      progressive shortening of refractoriness at a critical level with block and
      collision of wave fronts.

PMID- 8268837
TI  - Phenotypic and functional changes in chronic lymphocytic leukemia.
AB  - The study was carried out in 170 patients with chronic lymphocytic leukemia (CLL)
      at the onset, grouped according to RAI staging system, and in 20 controls. Using
      the rosette tests (E4 degrees, E 29 degrees, EAC and M) different lymphocytic
      subpopulations were detected. Their functional competence was studied by in vitro
      response to mitogens (PHA, PWM) and to an antigen (PPD). As it is well known the
      mean values of these parameters in CLL were found significantly reduced as
      compared to controls. But when compared according to the five clinical stages in
      CLL, two main aspects were observed. (a) stage 0 of the disease differs from the
      other clinical stages by the significantly low mean values of the parameters
      characteristic of the B cell line namely EAC rosetting and the in vitro response
      to PPD and PWM. Stage 0 of the disease is closer to the normal values; (b) the
      response of the PWM-stimulated T-dependent B cells decreases gradually and
      significantly with the clinical course of the disease and hence with the advance
      of clinical stages. The functional contribution of the various lymphocytic
      populations in this test is discussed as well as their possible implication in
      the pathogenesis of the disease.

PMID- 8268838
TI  - Minor axial tooth movement in preparation for fixed prostheses.
AB  - In this first of two articles the theory and practice of creating occlusal
      clearance for restorative procedures without the removal of tooth tissue is
      discussed. Earlier techniques for producing minor axial tooth movement are
      reviewed, together with the relevant literature on continuous eruption and
      occlusal stability. The indications for axial tooth movement and alternative
      treatment options are also considered.

PMID- 8268839
TI  - An in vitro assessment of cavity margin finishing and marginal adaptation of
      tunnel restorations.
AB  - Reasons for the failure of tunnel restorations include fracture of weak carious
      enamel at the cavity margins, poor adaptation of the restoration approximally,
      incomplete removal of caries and fracture of the marginal ridge. Four methods of
      cavity margin finishing were investigated. A round steel bur in a slow handpiece
      was found to give the best finish. Four materials were used for the restoration
      of tunnel cavities. In this study posterior resin composite gave the best
      marginal adaptation; however, a glass ionomer (polyalkenoate) may be preferable
      as it is impossible to guarantee removal of all carious tooth tissue from these
      preparations and glass ionomers have the benefit of fluoride release.

PMID- 8268840
TI  - Oral health status, treatment needs and demands of an elderly institutionalised
      population in Athens.
AB  - Oral health status, treatment needs and demands were investigated among 242
      elderly people (63 males and 179 females) living at the largest residential home
      in Athens. The mean age of the sample was 83.8 years (82.8 males and 84.1
      females). The oral health status was generally poor, 64.4% of the population were
      edentulous while 16.1% of them lacked dentures in both jaws. 43.2% of the
      subjects presented with denture-induced pathology of the oral mucosa, requiring
      either conservative or surgical treatment. The dentate subjects had an average of
      12.3 teeth with 4.2 teeth requiring extraction and 2.2 teeth with coronal
      restorable caries. The mean Root Caries Index was found to be 18.5%. The
      assessment of the periodontal treatment needs according to the CPITN revealed
      that 9.3% of the dentate subjects needed only oral hygiene instruction, 61.5%
      professional scaling and 20.9% more complex periodontal treatment. Although the
      total percentage of subjects needing some form of dental treatment was 85.1%,
      only 34% of them felt that they required it and only 13.1% had tried to obtain
      it.

PMID- 8268841
TI  - An examination of cingulum rest seats in incisor and canine teeth.
AB  - This study examined rest seats prepared in the cingula of incisor and canine
      teeth in terms of their form and their ability to offer denture support. Fifty
      rest seats prepared in vivo were examined and the fit of the denture framework
      was assessed at the trial insertion stage. Twenty two of the rests investigated
      showed no approximation (within 0.1 mm) between the casting and the floor of the
      rest seat. Investigations in vitro showed the provision of rest seats reduced the
      labial displacement of incisor and canine abutments under transmitted load
      compared to the same teeth without preparations.

PMID- 8268842
TI  - Tooth wear: an aetiological and diagnostic problem.
AB  - Tooth wear is an all-embracing term for attrition, abrasion and erosion which
      does not presuppose the mode of wear and allows for combined aetiology.
      Identification of the aetiology is essential for successful management. Known
      risk factors are discussed for attrition, abrasion and erosion. A combination of
      aetiologies complicates the diagnosis and may modify the clinical appearance or
      pattern of tooth wear. Examples of such cases are presented.

PMID- 8268843
TI  - An experimental evaluation of precision laser cutting of dental hard tissues and
      materials.
AB  - This paper examines the use of excimer laser radiation in the controlled removal
      of tooth tissue and three plastic restorative materials. Freshly extracted human
      third molar teeth were filled with three restorative materials and sectioned
      longitudinally through the restoratives. The cut surfaces of the materials and
      surrounding enamel and dentine were exposed to three laser energy densities and
      the dimensions and topographical details of the irradiated sites assessed using
      optical and scanning electron microscopy. The results showed that the radiation
      produced lesions of uniformly reproducible size and shape.

PMID- 8268844
TI  - Operating variables affecting the working time of a dual-cure composite luting
      cement.
AB  - Dual-cure composite resin luting cements are increasingly being used for the
      cementation of porcelain veneers, composite and ceramic inlays, onlays and
      crowns. This investigation assessed the effect of a dual-cure adhesive (Bondlite)
      on the working time of a dual-cure composite resin luting cement (Porcelite Dual
      Cure). An oscillating rheometer was used to measure the working time of the
      composite resin luting cement with and without prior application of dual-cure
      adhesive. The results demonstrated that use of the dual-cure adhesive
      significantly reduced the working time of the manufacturer's dual-cure composite
      resin luting cement.

PMID- 8268845
TI  - Guidelines for crown and bridgework.

PMID- 8268846
TI  - Application of limulus test (G pathway) for the detection of different conformers
      of (1-->3)-beta-D-glucans.
AB  - The reactivity of factor G mediated coagulation pathway in limulus amebocyte
      lysate which is triggered by (1-->3)-beta-D-glucans is thought to depend on the
      structure of the glucans, especially on the ultrastructure: triple helix, single
      helix and random coil. We used Sonifilan (SPG) and grifolan (GRN) as parent
      compounds to compare the reactivities of these three conformers. Under a neutral
      condition, alkaline treated SPG (SPG-OH, single helix) and polycarboxylated SPG
      (PC-SPG, random coil) showed significantly stronger reactivity than untreated SPG
      (triple helix). After the alkaline treatment, all three conformers showed
      comparable reactivities. It is suggested that the pretreatment of the glucan
      preparations by sodium hydroxide is quite important to compare quantitatively the
      reactivity of the glucans by limulus test, and comparing the data of untreated
      and alkaline treated glucans would provide information about their conformations.
      Using this approach, it was found that after heat treatment at around 150 degrees
      C, the conformation of GRN was changed to rich in the triple helix, and that
      following sodium hydroxide treatment and dialysis of GRN, the conformation of GRN
      was changed to single helix rich conformer. About half of the single helix
      conformer was gradually changed to triple helix conformer over one week at 4
      degrees C.

PMID- 8268847
TI  - trans-4-amidinocyclohexanecarboxylic acid 4-tert-butylphenyl ester, a trypsin
      inhibitor, blocks entry of HeLa cells from G2 phase into mitosis.
AB  - Release of HeLa cells arrested at the G1/S boundary by double-thymidine block
      immediately caused uptake of [3H]thymidine into DNA. The duration of the cell
      cycle time was 23 h and definite changes in cell density were observed between 12
      h and 13 h and also between 35 h and 36 h after removal of thymidine. Addition of
      trans-4-amidino-cyclohexanecarboxylic acid 4-tert-butylphenyl ester (ACHCA
      OPhBut), immediately after removal of the arrest had no effect on DNA synthesis,
      although it dose-dependently suppressed the first mitosis and the next round of
      DNA synthesis. While the addition of ACHCA-OPhBut at any time from 0 to 10 h
      after removal of thymidine suppressed mitosis, its addition after 11 h did not. A
      trypsin-like proteinase sharply appeared around 10 h 30 min and vanished within a
      few minutes. The proteinase activity seemed to be density dependent and was
      strongly inhibited by ACHCA-OPhBut. The effects of trans-4
      amidinocyclohexanepropionic acid 4-tert-butylphenyl ester (ACHPA-OPhBut), another
      trypsin inhibitor, on the proteinase activity and mitosis were more potent than
      those of ACHCA-OPhBut. These results suggest the involvement of the proteinase in
      the entry of HeLa cells from the G2 late phase into mitosis. The proteinase was
      named late G2 proteinase.

PMID- 8268848
TI  - Characterization of tumor necrosis factor alpha-induced alteration of
      glycosaminoglycans in cultured cells: comparison among vascular smooth-muscle
      cells, vascular endothelial cells, Chang liver cells and LLC-PK1 cells.
AB  - We investigated the alteration of glycosaminoglycans (GAGs) induced by
      recombinant human tumor necrosis factor alpha (rhTNF alpha) using confluent
      cultures of bovine aortic smooth-muscle cells, bovine aortic endothelial cells,
      Chang liver cells and porcine kidney LLC-PK1 cells. It was found that the
      incorporation of both [35S]sulfate and [3H]glucosamine into GAGs in the
      trypsinate fraction of the cell layer was significantly decreased by rhTNF alpha
      in vascular smooth-muscle cells and vascular endothelial cells; the incorporation
      of [35S]sulfate was increased but that of [3H]glucosamine was unchanged in Chang
      liver cells; the incorporation of both [35S]sulfate and [3H]glucosamine was
      increased by rhTNF alpha in LLC-PK1 cells. In the conditioned medium, the
      incorporation of both [35S]sulfate and [3H]glucosamine was not greatly changed by
      rhTNF alpha in all tested cell types. Characterization of GAGs revealed that each
      cell type uniquely altered its GAGs after rhTNF alpha treatment; the cytokine
      induced alteration of each GAG component was not necessarily the same among
      different cell types. It was therefore concluded that rhTNF alpha-induced
      alteration of GAGs is dependent upon cell type.

PMID- 8268849
TI  - Metabolic formation of dimethylamine and methylamine from basic drugs containing
      N-methyl group: a newly established chromatographic assay and its application to
      the determination of deaminase activity.
AB  - A new method of assaying deaminase activity was established in which methylamine
      and/or dimethylamine formed from drugs containing N,N-dimethyl or N-methyl group
      were derivatized with phenylisothiocyanate to phenylthiourea derivatives. After
      purification with Sep-PAK C18 cartridge, the derivatives were separated by a
      reversed phase high-performance liquid chromatography monitored by ultraviolet
      absorption. The recoveries and determination limits of methylamine and
      dimethylamine were over 55% and about 0.4 nmol/ml of incubation mixture,
      respectively. The method was used to measure the deaminase activities of liver
      microsomes of rats, rabbits and guinea pigs for 11 drugs. Of the compounds
      tested, diphenhydramine and diltiazem are deaminated with microsomes from all the
      above animal species; rat and rabbit liver microsomes also well deaminated
      promethazine. Most other drugs such as chlorpromazine, promazine, imipramine,
      amitriptyline and tetracaine were found to be poor substrates. In general,
      dimethylamine but not methylamine was the predominant metabolite formed from
      drugs containing N,N-dimethylamino group. The results also suggested that the
      deamination of these compounds takes place mainly via a one step mechanism, thus
      implying that the sequential reaction consisting of N-demethylation and
      elimination of ammonia is of minor importance. The relation between in vitro
      deaminase activity and the extent of the in vivo deamination for drugs is
      discussed.

PMID- 8268850
TI  - Identification of in vitro metabolites of 2,4,6,2',4',6'-hexachlorobiphenyl from
      phenobarbital-treated dog liver microsomes.
AB  - We studied in vitro metabolites of 2,4,6,2',4',6'-hexachlorobiphenyl (HCB, IUPAC
      PCB No. 155) produced by liver microsomes of a phenobarbital (PB)-treated beagle
      dog. The major metabolites were 3-hydroxy-2,4,6,2',4',6'-HCB (M-1), 4-hydroxy
      2,6,2',4',6'-pentachlorobiphenyl (PenCB, M-2) and 3,4-dihydroxy-2,6,2',4',6'
      PenCB (M-3). Furthermore, 4-hydroxy-2,3,6,2',4',6'-HCB (M-4), which could be
      formed via the 3,4-epoxidation and the subsequent NIH-shift of the chlorine from
      the 4 to the 3 position, was also detected. We found that M-3 is a common
      secondary metabolite of the two major monohydroxy metabolites, M-1 and M-2. These
      results indicate that the dog seems to metabolize and eliminate this congener not
      only by a mechanism involving direct insertion of a hydroxyl group but also via
      an arene oxide intermediate.

PMID- 8268851
TI  - Studies on pharmacological activation of human immunoglobulin G by chemical
      modification and active subfragments. X. Effect of carboxamidemethylated Fc
      fragment (CM-Fc) from human immunoglobulin G on delayed type hypersensitivity.
AB  - The anti-allergic activity of the carboxyamidemethylated Fc fragment (CM-Fc) from
      human serum immunoglobulin G (IgG) was studied using sheep red blood cell-induced
      delayed type hypersensitivity in mice (SRBC-DTH). CM-Fc suppressed the DTH
      response when administered 30 min before, or 4 h after the SRBC challenge, but
      not when administered 8 h or more after the challenge. The Fc fragment showed no
      activity. CM-Fc administration 30 min before the challenge was unable to suppress
      the DTH response in the cyclophosphamide (CY)-treated mice. However, adoptive
      transfer of splenocytes from mice treated with CM-Fc to CY-pretreated mice caused
      suppression of the SRBC-DTH response. These results suggest that CM-Fc suppressed
      the DTH response by mediating the function of CY-susceptible cells.

PMID- 8268852
TI  - Cytochrome P450 isozymes catalyzing the hepatic microsomal oxidation of 9
      anthraldehyde to 9-anthracene carboxylic acid in adult male rats.
AB  - Microsomal aldehyde oxygenase (MALDO) activity for 9-anthraldehyde (9-AA) was
      significantly higher in the male than in the female adult rat liver. 9-AA MALDO
      activity was also significantly enhanced by pretreatment with dexamethasone and
      phenobarbital, whereas it was not significantly changed by 3-methylcholanthrene
      or acetone. Several cytochrome P450 isozymes purified from rat hepatic microsomes
      were able to catalyze the oxidation of 9-AA to 9-anthracene carboxylic acid (9
      ACA) in the presence of NADPH, NADPH-cytochrome P450 reductase and
      dilauroylphosphatidylcholine. Under the ordinary conditions of the reconstituted
      system, the catalytic activities (nmol/min/nmol P450) of cytochrome P450s, 2A1,
      2B2, 2C6, 2C11 and 3A2 were 1.53 (1.37 in the presence of cytochrome b5), 1.20
      (2.06), 4.87 (7.75), 18.0 (21.6) and 0.90 (1.17), respectively. Cytochrome P450
      2C11 (CYP 2C11) showed the highest catalytic activity of the cytochromes
      examined. In the reconstituted system using the lipids extracted from microsomes,
      CYP 3A2 more effectively catalyzed the oxidation of 9-AA to 9-ACA, and its
      catalytic activity (nmol/min/nmol P450) was 3.33 or 6.61 in the absence or
      presence of cytochrome b5, respectively. The antibody against CYP 2C11 inhibited
      by 90% the hepatic microsomal oxidation of 9-AA MALDO activity in adult male
      rats, but the activity was not inhibited by antibody against CYP 3A2. These
      results show that the individual forms of cytochrome P450 have a catalytic
      activity for the oxidation of 9-AA to 9-ACA, and that CYP 2C11 is the major
      constitutive catalyst of 9-AA MALDO activity in untreated adult male rat liver.

PMID- 8268853
TI  - Glutathione levels of the human crystalline lens in aging and its antioxidant
      effect against the oxidation of lens proteins.
AB  - This paper reports the role of glutathione (GSH) in the crystalline lens as an
      antioxidant against the oxidation of lens protein. GSH levels in normal lenses
      decreased gradually with increasing age, from approximately 5 mumol per g lens
      (wet weight) to 3 mumol per g lens (wet weight). On the other hand, levels of
      oxidized GSH in the lenses increased until the age of 40. After that, it remained
      almost constant at the level of approximately 0.9 mumol per g lens. Protein-bound
      GSH levels in both soluble and insoluble lens proteins dropped noticeably in the
      50-year and older age groups, although there were significant differences in
      levels between both fractions. A decrease of tryptophan and tyrosine residues in
      lens proteins was proportional to a decrease in GSH levels in the lens as a
      result of aging. Those residue levels in the cataractous lenses were
      approximately half those in the normal lens proteins, and GSH levels in such
      lenses were almost one-tenth that in the normal lens. This study revealed that
      GSH may play an important role in preventing the oxidation of lens proteins from
      various oxidants. Furthermore, it is conceivable that these normal changes in GSH
      levels in the lenses increase the vulnerability of the lens to senile
      cataractogenesis.

PMID- 8268854
TI  - The synthesis and in vitro and in vivo stability of 5-fluorouracil prodrugs which
      possess serum albumin binding potency.
AB  - For a new drug delivery system of 5-fluorouracil, we prepared prodrugs possessing
      certain desired properties. The prodrugs, 1-(N-4-chlorophenyl-N-methylcarbamoyl)
      5-fluorouracil and 1-(N-2,4-dichlorophenyl-N-methylcarbamoyl)-5-fluorouracil,
      contain high serum albumin binding potency and a comparably long half life in the
      bloodstream in vivo to Tegafur. These two prodrugs are expected to be retained in
      the bloodstream as a polymeric complex with albumin and to circulate in the body
      for a long time, like a polymeric prodrug.

PMID- 8268855
TI  - Inhibition of c-Ha-ras gene expression by hammerhead ribozymes containing a
      stable C(UUCG)G hairpin loop.
AB  - Catalytic RNAs recognize specific sequences of RNA and cleave at a specific site.
      In this study, we designed hammerhead ribozymes with a thermodynamically stable
      loop of the sequence 5'C(UUCG)G3' to prevent the aggregation of ribozymes with
      hammerhead structures. The cleavage activities of these ribozymes were examined
      using a synthetic pentadecamer with the sequence for the c-Ha-ras mRNA mutated at
      codon 12 (GGU-->GUU). For in vivo studies, we constructed a plasmid which
      expressed a highly active ribozyme targeted against the mutated c-Ha-ras mRNA.
      When this ribozyme-encoding gene and the activated c-Ha-ras gene were
      cotransfected into NIH3T3 cells, morphologically normal cells were obtained. We
      also determined that the expression of the c-Ha-ras gene was inhibited in these
      cells. These results show that ribozymes containing this stable hairpin loop are
      useful for the regulation of specific gene expression in vivo.

PMID- 8268856
TI  - Transport mechanism of choline in rat renal brush-border membrane.
AB  - The transport mechanism of choline was examined using rat renal brush-border
      membrane vesicles in comparison with tetraethylammonium transport. The
      stimulatory effect of an outward H+ gradient on choline uptake was weak compared
      with that on tetraethylammonium uptake. [14C]Tetraethylammonium uptake was cis
      inhibited and trans-stimulated by choline, but the effects were less pronounced
      than those produced by unlabeled tetraethylammonium. [3H]Choline uptake was trans
      stimulated by unlabeled choline, but not by tetraethylammonium. An interior
      negative membrane potential induced marked stimulation of choline uptake against
      its concentration gradient (overshoot phenomenon), and the uptake was saturable
      with an apparent Km of 0.77 mM. Various compounds such as hemicholinium-3
      inhibited the choline uptake by renal brush-border membrane vesicles, but a
      sulfhydryl reagent did not. These findings suggest that choline can be actively
      transported by a carrier-mediated system driven by cell interior-negative
      membrane potential in renal brush-border membrane, and this system may play an
      important role in the tubular reabsorption of choline.

PMID- 8268857
TI  - Effectiveness of the elcatonin transdermal system for the treatment of
      osteoporosis and the effect of the combination of elcatonin and active vitamin D3
      in rat.
AB  - The efficacy of percutaneous elcatonin (EC), a hypocalcemic peptide, in the
      treatment of experimental osteoporosis in rats was evaluated in vivo.
      Additionally, the effect of the combined use of EC and active vitamin D3
      (1,25(OH)2D3) for the treatment was compared with those of three other groups:
      1,25(OH)2D3 alone, estradiol plus 1,25(OH)2D3, and a placebo, and low calcium
      diet (low Ca). The EC transdermal system and the EC plus 1,25(OH)2D3 system,
      applied to the rat abdominal skin 6 times for 48 h, significantly increased the
      ash weight and calcium content of the tibia in the rats, compared with those of
      placebo group (p < 0.05). The EC systems also slightly lowered the alkaline
      phosphatase activity in plasma of the morbid rats, without a difference in the
      plasma calcium content. These EC systems were superior to the 1,25(OH)2D3 system
      and the estradiol plus 1,25(OH)2D3 system in improving osteoporotic parameters.
      Thus, the EC systems were concluded to be an efficient drug delivery system for
      Paget's disease and osteoporosis.

PMID- 8268858
TI  - Identification of tissues responsible for the conjugative metabolism of
      liquiritigenin in rats: an analysis based on metabolite kinetics.
AB  - We kinetically examined tissues responsible for the conjugative metabolism
      (glucuronidation and sulfation) of a component in a crude drug, liquiritigenin
      (LG; 2,3-dihydro-7-hydroxy-2-(4- hydroxyphenyl)-(S)-4H-1-benzopyran-4-one) in
      rats in vivo. LG has been found to form five kinds of conjugates (4'-O
      glucuronide (M1), 7-O-glucuronide (M2), 4',7-O-disulfate (M3), 4'-O-glucuronide-7
      O-sulfate (M4) and 7-O-glucuronide-4'-O-sulfate (M5)). Analysis based on
      metabolite kinetics [K. S. Pang, J. Pharmacokin. Biopharm., 13, 633 (1985)] of
      the area under the plasma concentration curves (AUCplasma) and cumulative biliary
      excretions (Aibile) of the ligands after intravenous or hepatic portal venous
      administration of LG revealed that the liver has the ability to generate all the
      metabolites. For M1 and M2, the apparent biliary excretion clearance (CLbile,app)
      obtained by dividing the biliary excretion rate for the metabolite by the plasma
      concentration of the metabolite decreased with time, confirming that M1 and M2
      were formed in the liver. To further analyze the formation rate constants for
      metabolites in each tissue, we measured the ligand content in several tissues
      after intravenous administration of LG. By correcting the content of metabolites
      that were taken up from the plasma, we found that the formation rates per gram of
      tissue were largest in the liver, except for M3. The metabolic capability of the
      kidney for M1 and M2 was 15% and 60%, respectively, to that of the liver whereas
      for M3, the metabolic ability of the kidney was 2.5-fold greater than that of the
      liver.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268859
TI  - Evaluation of skin damage of cyclic monoterpenes, percutaneous absorption
      enhancers, by using culture human skin cells.
AB  - The cytotoxicity of monoterpenes, percutaneous absorption enhancers, to cultured
      human skin cells was investigated in order to quantitatively estimate their skin
      damage. A neutral red bioassay with epidermal keratinocytes and a contraction
      test of collagen gel in which dermal fibroblasts were cultured were employed for
      evaluating the cytotoxicity of terpenes. In the neutral red bioassay,
      keratinocyte proliferation was inhibited on the addition of terpenes, and cell
      survival remarkably decreased with an increase in the concentration of terpenes
      fed into the culture well. When the fibroblasts were cultured in a collagen gel
      matrix, the lattice of collagen contracted as the cells grew. Therefore, the
      application of cytotoxic agents brings about an inhibition of collagen gel
      contraction induced by the fibroblasts. Strong inhibition was observed in the
      cases of hydrocarbons in terpenes, and the inhibition was dependent on the
      concentration of these compounds added in the culture medium. The cytotoxicity of
      terpenes was compared with the skin damage evoked by the application of terpenes
      in rats in vivo. As a result, it was considered that the skin irritation caused
      by terpenes was predictable to a certain extent by means of the cytotoxic study
      of cultured human skin cells.

PMID- 8268861
TI  - Evaluation of quinaldine red as a fluorescent probe for studies of drug-alpha 1
      acid glycoprotein interaction.
AB  - We attempted to develop a fluorescent probe superior to conventional ones (8
      anilino-1-naphthalenesulfonate and auramine O) for use in the study of drug
      binding sites on alpha 1-acid glycoprotein (AGP). It was found that quinaldine
      red (QR) strongly bound to AGP and had an enhanced fluorescence in the presence
      of AGP at a longer wavelength, although QR was rarely fluorescent in an aqueous
      or albumin solution. The binding parameters of QR to AGP were K: 1.3 x 10(6) M-1
      and n: 0.9, using the fluorometric titration method. The fluorescence of QR in
      the AGP solution, however, was markedly quenched in the presence of basic drugs,
      indicating that these drugs competitively displaced QR from its binding site; the
      results were in good agreement with those in the literature. The good
      relationship between binding affinities and partition coefficients suggested that
      hydrophobic forces were involved in the binding of basic drugs to AGP. Moreover,
      the polarity of the binding site of AGP estimated from the relationship between
      the emission maximum of QR and Z values was 70, which corresponds to the same Z
      value of acetonitrile. These results distinguish QR from other conventional AGP
      probes as a better fluorescent probe by which to understand drug-AGP interaction
      and the characterization of binding sites on AGP in more detail.

PMID- 8268860
TI  - Inhibitory effects of NaCl and guanyl-5'yl-imidodiphosphate (GppNHp) on
      [3H]naloxone binding to kappa-opioid receptors in guinea pig cerebellum.
AB  - Studies were performed to characterize the opioid receptors in guinea pig brain
      using the radiolabeled opioid antagonists, [3H]naloxone and [3H]diprenorphine and
      the kappa-agonist [3H]U-69593. The binding of [3H]U-69593 to guinea pig
      cerebellar membranes was reduced by NaCl, guanyl-5'yl-imidodiphosphate (GppNHp)
      and NaCl+GppNHp, and [3H]naloxone binding to cerebellar membranes was also
      reduced by NaCl and GppNHp. In the guinea pig cerebral cortex and striatum and
      the rat cerebellum, [3H]naloxone binding was not affected significantly by GppNHp
      in the presence or absence of 100 nM [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO)
      and [D-Ala2, D-Leu5]enkephalin (DADLE). Guinea pig cerebellar [3H]diprenorphine
      binding was not affected by NaCl, GppNHp or NaCl+GppNHp. Furthermore,
      [3H]naloxone binding was reduced after pretreating cerebellar membranes with N
      ethylmaleimide (NEM), which also attenuated GppNHp-induced inhibition of
      cerebellar [3H]naloxone binding. These results suggest that the properties of
      [3H]naloxone binding in guinea pig cerebellum differ from those in other brain
      regions and rat cerebellum, and that the interaction of [3H]naloxone and [3H]U
      69593, but not [3H]diprenorphine, with guinea pig cerebellar opioid receptors is
      associated with a G-protein.

PMID- 8268862
TI  - Anti-tumor promoting activities of natural products. II. Inhibitory effects of
      digitoxin on two-stage carcinogenesis of mouse skin tumors and mouse pulmonary
      tumors.
AB  - Two-stage carcinogenesis of mouse skin papillomas induced by 7,12
      dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA),
      and mouse pulmonary tumors induced by 4-nitroquinoline-N-oxide (4NQO) and
      glycerol, were inhibited by digitoxin (1).

PMID- 8268863
TI  - Mitogenic activity and lethal toxicity of lipid A analogs, glucosamine-phosphate
      carrying aromatic alkyl groups, in mice.
AB  - The mitogenicity and lethal toxicity of four synthetic lipid A analogs,
      glucosamine-4-phosphate with a 7-hydroxy-heptanoyl group (A-166), with a 7-phenyl
      heptanoyl group (A-167), or with a 8-(1-phenyl-hexanoyl)-nonanoyl group (A-168),
      at the C-2 and C-3 positions, and glucosamine-6-phosphate with the same
      substituents as A-168 at C-2 and C-3 (A-169), were compared. The compound A-166
      exhibited no mitogenic activity at various concentrations ranging from 3.13 to 50
      micrograms/ml in the splenocytes of BALB/c mice, but A-167 exhibited weak
      mitogenic activity at concentrations of 12.5 and 25 micrograms/ml. A-168 and A
      169, as well as A-103, glucosamine-4-phosphate carrying (R)-3-tetradecanoyl
      oxytetradecanoyl groups, have remarkable mitogenic activity at concentrations
      ranging from 12.5 to 100 micrograms/ml; the activity of A-169 (6-phosphate) was
      stronger than that of A-168 (4-phosphate). Compound A-167 failed to cause death
      at doses of 25 and 50 micrograms/mouse in galactosamine-loaded C57BL/6 mice while
      A-166 and A-169 were toxic to 2 out of 6 mice at 50 micrograms/mouse; no deaths
      were observed at 25 micrograms/mouse. A-168 showed the highest toxicity of any of
      the compounds tested at 25 and 50 micrograms/mouse. The lethal effect of A-103
      appeared to be somewhere between that of A-168 and A-169. These findings indicate
      that lipid A analogs, carrying an aromatic alkyl group as well as a hydroxyacyl
      group, are mitogenic and lethal when given to mice.

PMID- 8268864
TI  - Pharmacological properties of galenical preparation. XVI. Pharmacokinetics of
      evodiamine and the metabolite in rats.
AB  - In an attempt to evaluate its pharmacokinetics, [3H]evodiamine, which is one of
      the characteristic alkaloids of Evodia fruit was synthesized. The
      pharmacokinetics of [3H]evodiamine were investigated in rats. In plasma, the main
      source of radioactivity was a metabolite of d-evodiamine (EM). One hour after
      oral administration of 200 micrograms/kg of [3H]evodiamine, the radioactivity
      level in the plasma was maximal. The radioactivity declined in a biphasic manner
      with half-life times of 1.6 and 78.4 h. The distribution volume was 560 ml/kg.
      Radioactivity in tissues was higher in the liver, kidney, heart, lung, and
      adipose tissue than in plasma, but radioactivity in other tissues it was lower
      than that in plasma. In all tissues the radioactivity proportionally decreased to
      the level of that in plasma. At 24h after administration, 19% and 63% of orally
      administered radioactivity was excreted in urine and bile, respectively.

PMID- 8268865
TI  - Uptake of fluorescein isothiocyanate (FITC)-fractionated heparin by rat
      parenchymal hepatocytes in primary culture.
AB  - The distribution of fractionated heparin in a primary culture of rat parenchymal
      hepatocytes was investigated optically using the fluorescence labelled drug and
      confocal imaging system with an inverted fluorescence microscope. The cell
      associated fluorescein isothiocyanate (FITC)-fractionated heparin was observed to
      increase in conjunction with incubation time and also to localize, suggesting an
      internalization to cell organella with the exception of the nuclei.

PMID- 8268866
TI  - Mutagenic activities of chiral epoxides, halides, and N-nitrosoamines.

PMID- 8268867
TI  - Structural analysis of a low-sulfated chondroitin sulfate chain in human urinary
      trypsin inhibitor.
AB  - The low-sulfated chondroitin 4-sulfate(LSC) chain from human urinary trypsin
      inhibitor was purified and the structure was characterized. After hyaluronidase
      SD digestion of LSC, an oligosaccharide which contains the linkage region could
      be obtained. The structure of oligosaccharide was analyzed by HPLC and 500 MHz 1H
      NMR spectroscopy. The analytical results revealed that 4-O-sulfo GalNAc residues
      were located in the neighborhood of the linkage region.

PMID- 8268868
TI  - Hypertension in Latin America: importance and approaches to control.
AB  - Although data on prevalence of hypertension are very scarce available information
      show that hypertension is as frequent in Latin America as in Europe and USA.
      Morbidity and mortality data place hypertension as the leading cause of death and
      disability in virtually all countries in Latin America. New demographic changes
      point to an increase in the number of older age groups in Latin America. This
      will further increase the importance of hypertension as a public health problem.
      Urgent actions aiming to increase detection and treatment of hypertension are
      needed. Emphasis on risk factors may be particularly effective due to economic
      restrains.

PMID- 8268869
TI  - Hypertension studies in China.
AB  - In China, hypertension (HT) prevalence increased from 7.7% in 1980 to over 11% in
      1991. The higher prevalence of HT in the north and among urban populations may be
      due in part to higher body mass index (BMI) levels and dietary composition.
      Community control of HT has been organized since 1969. Reports from centers with
      a history of community control for over 10 years have indicated a 40% and 34%
      decrease respectively in the incidence of stroke and acute myocardial infarction
      (AMI). Sino-Monica Beijing Project shows that morbidity and mortality of stroke
      and coronary heart disease are higher in north China and urban centers, stroke is
      4-8 times higher than coronary events. The trend from 1985-1989 was relatively
      steady. Although the mortality of stroke and AMI was decreasing, the case
      fatality rate remained high, and the rapid increase in the proportion of older
      population points to an urgent need for a nationwide prevention and control
      program.

PMID- 8268870
TI  - Left ventricular hypertrophy and hypertension.
AB  - The level of left ventricular (LV) mass as measured by echocardiography or other
      techniques in hypertensive patients reflects the integrated effects of the level
      of arterial pressure, the concomitant volume load imposed on the heart, and of
      alterations in arterial waveform morphology as well as of body size and non
      hemodynamic variables. The LV may respond to these stimuli by concentric or
      eccentric hypertrophy or by the recently-described pattern of concentric
      remodeling, in which LV mass is normal but relative wall thickness is increased.
      The are strong parallelisms between increases in cardiac and systemic arterial
      wall thicknesses, and patients with discrete atheromas detectable by carotid
      ultrasound have elevated LV masses. Patients with eccentric and concentric LV
      hypertrophy have two to four-fold increases in the incidence of cardiovascular
      morbid events compared to hypertensive patients with normal LV geometry, and the
      change in LV mass during treatment has been associated with the risk of
      subsequent morbidity in initial studies. In contrast to the strong predictive
      power of LV geometric assessment, use of indirect measures of target organ status
      in the WHO system for classification of the severity of hypertension does not
      improve on the prediction of prognosis that can be obtained by consideration of
      the level of arterial pressure. Current evidence suggests that evaluation of LV
      geometry may contribute to improved clinical decision-making in situations where
      more precise stratification of risk would clarify whether or not to institute
      treatment, or whether it should be with drugs or non-pharmacologic measures.

PMID- 8268871
TI  - Behaviour of conduit arteries in hypertension.
AB  - Through an increase in vascular resistance, changes of the small arteries are
      responsible for the evaluation of mean arterial pressure in hypertension.
      However, the amplitude of the pressure oscillation, i.e. pulse pressure, is
      influenced by other hemodynamic mechanisms, which involve large arteries through
      a decrease in compliance and an increase in wave reflections. Consequently,
      structural and functional alterations of the large arteries are responsible in
      hypertensive subjects for an increase in the amplitude of the pressure
      oscillation and a disproportionate increase in systolic pressure over diastolic
      blood pressure through arterial (and not arteriolar) changes. Such findings not
      only contribute to a better understanding of the relationships between vascular
      structure and function and the level of blood pressure but also to better
      interprate the hypertensive complications, particularly those related to the
      heart and larges vessels.

PMID- 8268872
TI  - Insulin resistance and hypertension.
AB  - In non obese, nondiabetic patients, essential hypertension is associated with an
      insulin resistance that is peripheral in location and metabolically selective.
      The correlations between hyperinsulinemia, insulin resistance and blood pressure
      values do not prove that the relationship is a causal one. Different data support
      this hypothesis, however, the demonstration in humans that insulin resistance
      play a central role in the development of essential hypertension and coronary
      heart disease is still lacking. The relative current failure of coronary heart
      disease prevention in hypertensive patients may be related to the metabolic side
      effects of diuretics and beta-blockers. These drugs increase insulin resistance
      and lipid disorders. Angiotensin-converting enzyme inhibitors and calcium
      antagonists do not decrease insulin sensitivity neither alter lipid profile.
      Angiotensin-converting enzyme inhibitors and calcium antagonists have
      significantly improve compliance to pharmacological therapy, however their use
      has been associated with a dramatic cost increase and we do not yet know if they
      would reduce morbidity and mortality as well as or better than older and cheaper
      antihypertensive agents. Nonpharmacological interventions are usually very
      effective to reduce insulin resistance and the different cardiovascular risk
      factors present in most hypertensive patients. To improve patient's compliance to
      diet and regular exercise we have to develop new strategies.

PMID- 8268873
TI  - Microalbuminuria in essential hypertension.
AB  - The prevalence and significance of microalbuminuria is not well elucidated in
      patients with essential hypertension. In newly detected hypertension, its
      prevalence ranges between 23 and 37% and albuminuria is usually well correlated
      with the level of arterial pressure. Interestingly, albuminuria is enhanced in
      overweight hypertensive patients. Antihypertensive treatment has variable
      influence on albuminuria, and converting enzyme inhibitors, in contrast to other
      agents, tend to partially correct this abnormality. Whether microalbuminuria
      represents a predictor of the future development of nephrosclerosis and
      ultimately renal failure, or a predictor of cardiovascular morbidity deserves to
      be investigated.

PMID- 8268874
TI  - Early detection of subclinical atherosclerosis in asymptomatic subjects at high
      risk for cardiovascular disease.
AB  - Subclinical atherosclerosis can be non-invasively detected via calcifications,
      thickening and stiffening of arteries. Coronary calcifications seen with
      ultrafast computed tomography are frequent in hypertension or
      hypercholesterolemia and synonymous of coronary atherosis but not of coronary
      stenosis. Wall thickening detectable by extracoronary ultrasonography may be
      characterized by an intimamedia thickening shown in hypertension or by a
      focalized plaque whose the presence in the aortic or femoral level seem
      influenced by systolic pressure. Extracoronary wall thickening may be an aid in
      the diagnosis of coronary atherosclerosis, a predictor of coronary event, and a
      therapeutic target. Wall stiffening, which reflects sclerosis, is detected by
      pulse wave velocity. Its increase in hypertension may be an indicator of
      atherosclerosis and can be reversed by certain antihypertensive agents. Clinical
      care of at risk individuals might profit from subclinical atherosclerosis which
      adds objectivity and sensitivity in the individualization of risk and the
      decision to treat.

PMID- 8268875
TI  - A multifactorial approach to coronary disease risk assessment.
AB  - Coronary heart disease (CHD) remains a major cause of morbidity and mortality in
      Western societies. Hypertension has been identified as a cardinal risk factor for
      CHD. Guidelines for hypertension classification and treatment are based on the
      results of clinical trials that have demonstrated reductions in cardiovascular
      endpoints in treated hypertensive patient. Controversy persists regarding the
      level of blood pressure at which treatment should be initiated and the desirable
      blood pressure goals of treatment. Several algorithms for CHD risk prediction
      have been developed. This report will review one recently developed approach for
      predicting CHD risk based upon observational data from the Framingham Heart
      Study. A rationale is presented for considering absolute level of CHD risk to
      guide hypertension treatment.

PMID- 8268876
TI  - Evaluation of blood pressure measuring devices.
AB  - Validation of blood pressure measuring devices is a relatively new field of
      research. There are two national protocols for validating blood pressure
      measuring devices: the protocol of the American Association for the Advancement
      of Medical Instrumentation (AAMI) and the protocol of the British Hypertension
      Society (BHS), each of which has recently been revised. 19 blood pressure
      measuring devices have been validated according to one or both of these
      protocols. These protocols have been beneficial in drawing attention to the
      potential inaccuracy of blood pressure measuring systems, they permit comparison
      between devices and they have brought manufacturers of blood pressure measuring
      devices into closer contact with the profession. There are some inherent
      weaknesses in both protocols which include the fallibility of the 'gold
      standard', the lack of provision for validation in special circumstances and in
      special groups, such as the elderly and pregnant women, and failure to allow for
      deteriorating accuracy with higher pressure levels. The revised BHS protocol
      attempts to redress these deficiencies.

PMID- 8268877
TI  - Ambulatory blood pressure monitoring in hypertension.
AB  - Ambulatory blood pressure monitoring generates a greater interest among
      investigators and clinicians because of its potential to 1) study the mechanisms
      involved in cardiovascular control in daily life (particularly if monitoring is
      performed on a beat-to-beat basis) and 2) improve the diagnosis of hypertension,
      the estimate of the patient's risk and the assessment of the efficacy of
      antihypertensive treatment. This paper will discuss the evidence pros and cons
      the latter indications of this approach. It will be shown that 24 hour blood
      pressure values correlate more closely than clinic blood pressure with various
      measures of the end organ damage of hypertension, suggesting that it may reflect
      better than traditional blood pressure measurements the cardiovascular
      consequences of this condition. Wider use of ambulatory blood pressure monitoring
      in the medical practice, however, must await a more clear demonstration of its
      prognostic importance, by longitudinal studies based on cardiovascular morbidity
      and mortality or on surrogate end points with undisputable clinical significance
      (e.g. left ventricular hypertrophy). It must also await clear definition of
      ambulatory blood pressure normality based on population studies. Until then
      ambulatory blood pressure monitoring should be employed to resolve special
      problems, e.g. identification of white coat hypertension and false non response
      to treatment.

PMID- 8268878
TI  - Self blood pressure measurement at home.
AB  - Forty-six untreated patients measured their blood pressure at home for three
      weeks using an A and D, UA 751 automatic device, and were examined three times at
      the outpatient clinic. Home blood pressure was significantly lower than clinic
      blood pressure, even at the third visit when the correlations between clinic and
      home values were the most significant. The differences between clinic and home
      values had a gaussian distribution. The variance analysis of home blood pressure
      values showed that 67% of the variance was attributable to the between-subject
      component, 2% to the day effect, 15% to the time of the day effect and 16% to the
      residual (the measurement error). The standard deviation of the difference
      between two five-day periods of self blood pressure monitoring at home (5.4 and
      4.1 mm Hg) was much lower than what has been reported for clinic measurements or
      24-hour ambulatory monitoring.

PMID- 8268879
TI  - Compliance to treatment.
AB  - One major challenge of hypertension management is to achieve a compliance rate as
      high as possible in order to guarantee a successful long-term antihypertensive
      therapy. Clinical studies have shown that the drop-out rate may represent an
      indirect parameter for patient compliance. As having a negative influence on long
      term compliance drug related side effects are best known but newer results
      indicate that there are also other factors like age, sex, psychological features
      and quality of life do have important influence on compliance. For achieving the
      therapeutic aim strategies like simple prescription, few concomitant medication
      and cautious dose-titration have shown to be efficient. Additional blood pressure
      self-measurement and profound instruction are essential to optimize hypertension
      management in terms of compliance to treatment.

PMID- 8268880
TI  - Cost-effectiveness of the treatment of hypertension.
AB  - Cost-effectiveness and cost-utility analyses are defined and examples given of
      their use in a trial comparing the use of propranolol with verapamil. Eight other
      analyses are considered that look at the cost-effectiveness of anti-hypertensive
      treatment in general and at comparisons of such treatments. The analyses are
      examined to see if conclusions are made for different ages and both sexes;
      whether compliance with treatment is considered, and whether discounting, the
      cost of treating side effects and the effects of cholesterol were considered. The
      methods of estimating life years gained are examined and, if epidemiological data
      were employed, the fraction of benefit (FOB) assumed. The levels of blood
      pressure are examined together with the methods of estimating the quality of life
      adjusted years of survival (QALYS) in cost-utility analyses. It is concluded that
      large trials are required in which both survival on different treatments is
      measured together with costs and the quality of life of the individual patients.
      Cost-effectiveness and cost-utility is more favourable in men than women and in
      the elderly. There is no agreement as to which drug group has the most
      advantageous cost-utility.

PMID- 8268881
TI  - Hypertension management in populations.
AB  - A variety of lifestyle modification and drug therapies can be used to treat
      hypertension. Hypertension awareness, as well as drug treatment, and control
      rates have improved progressively in the United States during the last three
      decades. The extent to which lifestyle modification interventions are being
      utilized to treat hypertension is uncertain. There has been a progressive shift
      from antihypertensive drug therapy with diuretics and beta blockers toward
      treatment with newer and more expensive agents such as calcium channel blockers
      and angiotensin converting enzyme inhibitors. The newer agents are well tolerated
      and effective in lowering blood pressure but their efficacy in preventing
      cardiovascular disease complications is less well documented. In order to reduce
      the burden of blood pressure-related cardiovascular disease in the general
      population, treatment of hypertension must be complemented by a parallel strategy
      to prevent hypertension.

PMID- 8268882
TI  - Alcohol, hypertension and cardiovascular disease--implications for management.
AB  - Regular alcohol consumption raises blood pressure and in drinking populations
      contributes significantly to the prevalence of hypertension. The effect of
      alcohol is additive to that of obesity. Reduction in alcohol intake leads to a
      lowering of blood pressure over 1-4 weeks. Acute alcohol ingestion in the evening
      may lower blood pressures overnight. Heavy weekend drinking may lead to a pressor
      effect for the succeeding 3 to 4 days. Certain personality types or heavy job
      strain increase susceptibility to pressor effects of alcohol. Alcohol consumption
      in the range of 1-3 standard drinks a day appears to have a protective effect
      against coronary disease and ischaemic stroke, which may be greater in those with
      a higher risk of vascular disease. At higher levels of consumption the risks of
      haemorrhagic stroke, cardiomyopathy and hypertension deaths predominate.
      Moderation of alcohol consumption to no more than two standard drinks a day can
      be an effective means of improving blood pressure control reducing drug
      requirements in treated hypertensives, and avoiding drugs in mild hypertensives.
      Moderating alcohol and reducing excess weight have additive effects in reducing
      overall cardiovascular risk.

PMID- 8268883
TI  - Hypertension and exercise.
AB  - A sedentary lifestyle may be a risk for hypertension, according to the results of
      both cross sectional and longitudinal studies. However, exercise may reverse the
      adverse effects of lack of activity. Many controlled studies have shown that
      exercise lowers systolic/diastolic blood pressure by at least 10/5 mmHg. Exercise
      not only improves blood pressure, but also attenuates other risk factors for
      cardiovascular complications. Dynamic isotonic exercise (e.g., weight lifting).
      Milder (e.g., brisk walking for 30-60 minutes/day) rather than moderate to severe
      exercise (e.g., running) is also recommended because of similar effectiveness and
      better compliance. The underlying mechanism of action of exercise on blood
      pressure seems to be multifactorial involving a decrease in pressor factors such
      as plasma norepinephrine, the serum Na/K ratio, endogenous ouabain-like substance
      and erythrocyte mean corpuscular volume, as well as an increase in depressor
      factors such as plasma prostaglandin E, serum taurine and urinary dopamine
      excretion.

PMID- 8268884
TI  - Smoking and hypertension.
AB  - Coronary heart disease is the most common cause of death in hypertensives--about
      twice as common as stroke. Smoking increases this raised risk of hypertension by
      some 2 to 3 times. Surprisingly perhaps, this increased risk from smoking
      declines rapidly on quitting--within 2-3 years. Smoking increases the risks of
      vascular damage by increasing sympathetic tone, platelet stickiness and
      reactivity, free radical production, damage to endothelium, and by surges in
      arterial pressure. The latter may interfere with the action of some hypotensive
      agents. Persuading hypertensive patients not to smoke is the single most
      effective measure we can take to reduce their risk.

PMID- 8268885
TI  - Combinations of lifestyle modification and drug treatment in management of mild
      moderate hypertension: a review of randomized clinical trials.
AB  - Several randomized clinical trials have compared combined lifestyle and drug
      treatment of hypertension to drugs alone, lifestyle alone, or no treatment.
      Lifestyle interventions tested have included: weight loss, sodium reduction,
      potassium increase, and combinations of these and other modalities. Each trial
      has found combined therapy to be superior to the comparison group(s) in terms of
      blood pressure reduction and/or control, or to amount of drugs required, except
      in the U.S. TAIM study for the sodium/potassium regimen, where the lifestyle
      changes were small. Combined therapy has also been consistently better regarding
      side effects/quality of life, and there is evidence for greater reduction in
      cardiovascular risk. Some findings suggest variation among drugs for optimal
      combinations. Information on cost-effectiveness is lacking.

PMID- 8268886
TI  - New avenues in antihypertensive drug treatment.
AB  - After a brief synopsis of the classical antihypertensive drugs a survey is given
      of the newer therapeutics, such as calcium antagonists, ACE-inhibitors and alpha
      1-adrenoceptor antagonists. Experimental drugs, such as imidazoline receptor
      agonists, renin inhibitors, angiotensin II receptor antagonists, alpha 2
      adrenoceptor antagonists, potassium channel openers, ketanserin, endopeptidase
      inhibitors, and hybrid (multifactorial) drugs are discussed, with special
      attention for their modes of action. In spite of the ever increasing number of
      antihypertensive drugs and principles, the large scale of clinical evidence for a
      beneficial effect of long-term treatment (in particular with respect to
      protection against stroke) remains limited to diuretics and beta-blockers. In
      spite of this limitation it seems worthwhile to consider the newer
      antihypertensive drugs as well, especially for optimal treatment of the
      individual patient. The newer drugs may in particular offer special advantages in
      the presence of concomitant diseases, such as diabetes mellitus, hyperlipidaemia,
      angina pectoris or congestive heart failure.

PMID- 8268887
TI  - Angiotensin II antagonists.
AB  - Acute blockade of the renin-angiotensin system with the parenterally active
      angiotensin II antagonist saralasin has been shown to effectively lower blood
      pressure in a large fraction of patients with essential hypertension and to
      improve hemodynamics in some patients with congestive heart failure. It is now
      possible to antagonize chronically angiotensin II at its receptor using the non
      peptide angiotensin II inhibitor losartan (DuP 753, MK 954). When administered by
      mouth, this compound induces a dose-dependent inhibition of the pressor response
      to exogenous angiotensin II. This effect is closely related to circulating levels
      of the active metabolite E3174. Preliminary studies performed in hypertensive
      patients suggest that losartan has a blood pressure lowering action equivalent to
      that of an ACE inhibitor. Whether this compound will compare favorably with ACE
      inhibitors requires however further investigation.

PMID- 8268888
TI  - The place of diuretics in the treatment of hypertension in 1993: can we do
      better?
AB  - Diuretics are the only class of antihypertensive drugs that have been
      conclusively shown to reduce morbidity and mortality in long term outcome trials.
      However even in these trials there were difficulties with withdrawals, cross
      contamination, high usage of 2 or more drugs and adverse effects. Low doses of
      thiazide diuretics should be recommended because they have equal blood pressure
      lowering effects with less biochemical changes and adverse reactions. In 3 of the
      4 outcome trials in the elderly in which there were significant reductions in
      cardiovascular morbidity and mortality a potassium sparing agent was used in
      conjunction with the thiazide diuretic, raising the possibility of additional
      cardioprotection.

PMID- 8268889
TI  - Calcium channel blockers in current medical practice: an update for 1993.
AB  - Calcium channel blocking drugs (CCB) have been used to lower blood pressure since
      1970. Three classes are currently available, the phenylalkylamines, the
      benzothiazepines, and the dihydropyridines. The structure of the L-type, voltage
      dependent calcium channel has been elucidated with molecular techniques and the
      different binding sites of the various CCB described. CCB have specific effects
      at the site of target organs. In the kidney, all classes produce natriuresis.
      Their action appears independent of the level of salt intake. CCB may favorably
      influence the course of chronic renal disease; the results of a trial comparing
      nifedipine to the converting enzyme inhibitor captopril showed no difference
      between the two drugs. CCB may impede the progression of atherosclerosis in the
      coronary arteries; a prospective study of nifedipine on coronary artery
      morphology supports this view. In the brain, nimodipine improves the outcome of
      patients with stroke from subarachnoid hemorrhage. Positive effects on patients
      with ischemic stroke have not been corroborated. CCB are approved primary
      treatment for patients with hypertension and are readily combined with other
      antihypertensive agents. They are well tolerated and have no adverse metabolic
      side effects. The advent of molecular pharmacology will advance current efforts
      to develop new CCB, which are highly selective in their site and mode of action.

PMID- 8268890
TI  - Angiotensin-converting enzyme inhibitors in the treatment of mild arterial
      hypertension.
AB  - Angiotensin-converting enzyme inhibitors are nowadays widely employed for the
      treatment of arterial hypertension. They exhibit comparable levels of efficacy
      and better tolerability when compared with the other antihypertensive agents. In
      mild arterial hypertension they have been shown to be more efficacious than
      nonpharmacological therapy that is recommended as the first-step therapeutic
      approach for most cases of this type of hypertension. Potential advantages for
      the control of associated metabolic risk factors and specific renal and cardiac
      effects make these drugs suitable for the first step pharmacological therapy on
      mild hypertension.

PMID- 8268891
TI  - The place of combination therapy in the treatment of hypertension in 1993.
AB  - "Step Care" fell into disuse following the advent of the ACE inhibitors and
      calcium antagonists. This was partly because the potency of these agents
      encouraged their use in monotherapy, and partly because of dissatisfaction with
      ritual treatment using multiple drugs. However monotherapy too has its problems,
      not the least of which is ritual increase in the dose of the first drug
      prescribed, leading to prolonged treatment with high doses and hence an increase
      in side effects. It is therefore important to consider changing to an alternative
      drug rather than automatically increasing the dose, or adding a second drug.
      Combination therapy still has a major place in the treatment of hypertension. It
      is necessary in patients with severe hypertension, with clinical manifestations
      of target organ damage, or with associated conditions that often help the doctor
      to choose a rational combination. Even in patients with uncomplicated mild
      hypertension, the achievement of goal blood pressure requires combination therapy
      in around half the cases. By choosing two drugs from appropriate classes of
      agent, it is possible to add the primary actions of drugs acting through
      different mechanisms, while opposing the homeostatic compensations that limit the
      fall in blood pressure. Effective combinations therefore maximise hypotensive
      efficacy while minimising side effects. Effective combinations for the treatment
      of classical and of systolic hypertension, are discussed.

PMID- 8268892
TI  - Hypertension in childhood and adolescence.
AB  - Through the benefit of a large body of normative data on blood pressure
      throughout childhood, along with the clinical practice of regular blood pressure
      measurement in the young, mild elevation of blood pressure can be detected in the
      young. Unlike secondary hypertension in the young which is more severe, slight to
      mild elevations in blood pressure during childhood may be an early expression of
      essential hypertension. Mildly elevated blood pressure in the young is usually
      associated with other risk factors including obesity, family history of
      cardiovascular disease, and metabolic alterations in lipids and insulin.
      Environmental factors, which include health related behaviors can modulate the
      expression of the risk factors including elevated blood pressure. The extent to
      which the health behaviors of diet and exercise can be modified in the young may
      be important for risk factor intervention during the early phases of
      hypertension.

PMID- 8268893
TI  - Hypertension and diabetes.
AB  - Co-presentation of hypertension and diabetes leads to a significantly greater
      increase of cardiovascular mortality than each disease separately. Hypertension
      appears to be not only a complication of diabetes but apparently also shares a
      common pathogenetic mechanism, particularly in non-insulin dependent diabetes.
      Recent data suggest alterations in the nocturnal decline of blood pressure in
      diabetics, which together with microalbuminuria, may prove to be a predictor of
      nephropathy and hypertension. When hypertension occurs in diabetics, it requires
      a vigorous therapeutic approach. Nevertheless, the presence of diabetes modifies
      the requirement for first line therapy, particularly with respect to potential
      alterations of metabolic homeostasis in order to effectively prevent
      cardiovascular complications.

PMID- 8268894
TI  - Hypertension in the elderly.
AB  - Several studies have demonstrated an increased risk of cardiovascular disease
      (CVD) in relation to high blood pressure in elderly patients aged below 70-75,
      whereas the risk seemed to decline with age in the older elderly. Early studies
      on the effect of treatment of mild to moderate hypertension in the elderly
      indicated (but did not convincingly show) a reduction of CVD. In the 1980s, both
      the EWPHE trial (European Working Party on High Blood Pressure in the Elderly)
      and the HEP study (The Randomised Trial of the Treatment of Hypertension in
      Elderly Patients in Primary Care) provided evidence of the benefit of treating
      high blood pressure in the elderly, at least up to the age of 70-74. These
      results have lately been confirmed by three major trials SHEP (Systolic
      Hypertension in the Elderly Program), STOP (Swedish Trial in Old Patients with
      Hypertension) and MRC (Medical Research Council), also including older patients
      (STOP) and those with isolated systolic hypertension (SHEP). This satisfactory
      effect was not impaired by a low tolerability of the drugs used (beta-blockers
      and diuretics). In conclusion, drug treatment with beta-blockers and diuretics in
      hypertensive men and women aged 70 and above confers highly significant and
      clinically relevant reductions in cardiovascular (especially stroke) morbidity
      and mortality. The clinical implication of this is that blood pressure lowering
      therapy should be considered in elderly hypertensives, at least up until they are
      80. It should also be remembered that elderly hypertensives often have other
      diseases as well and that the drug treatment should be adjusted accordingly.

PMID- 8268895
TI  - Hypertension in pregnancy.
AB  - Hypertension in pregnancy is still one of the most important causes of maternal
      morbidity and mortality. Several different definitions are used, partly because
      the pathogenetic background to the hypertensive diseases of pregnancy is not
      known. Widely variable incidences have been reported in different populations,
      but a reasonable estimation is that less than 5% of pregnancies are complicated
      by clinically relevant blood pressure elevation. The treatment of hypertension in
      pregnancy has been a matter of debate, but in late pregnancy, there is agreement
      that delivery is the treatment of choice. In later years, antihypertensive drugs
      have been less used in mild or moderate hypertension in pregnancy. Low-dose
      aspirin may be useful as a preventive treatment in high-risk pregnancies, but
      final proof of this is still lacking. Long term follow-up of women with a
      hypertensive pregnancy is important, since a significant proportion of these
      women will develop later chronic (essential) hypertension, even if their blood
      pressure is completely normalised shortly after delivery.

PMID- 8268896
TI  - IX-1993 guidelines for management of mild hypertension. WHO/ISH Mild Hypertension
      Liaison Committee.

PMID- 8268897
TI  - Proceedings of the Joint WHO/ISH Symposium on Hypertension and Cardiovascular
      Disease. Paris, March 28-31, 1993.

PMID- 8268898
TI  - Conclusions and implications of the systolic hypertension in the elderly program.
AB  - Isolated systolic hypertension has a higher prevalence with age and an associated
      excess cardiovascular risk. The Systolic Hypertension in the Elderly Program
      (SHEP) was a randomized, prospective, double blind clinical trial to assess the
      efficacy and safety of a antihypertensive regimen based on low dose diuretic
      therapy in reducing the five year combined incidence of fatal and nonfatal
      stroke. SHEP demonstrated a significant 36% reduction in stroke incidence. Also,
      27% reduction in coronary heart disease incidence and a 32% reduction in major
      cardiovascular disease incidence were achieved. The benefits accrued to all
      subgroups identified based on baseline age, race, sex, blood pressure, serum
      cholesterol levels, and ECG abnormalities. A low-dose diuretic regimen should be
      the initial treatment of choice for most hypertensive patients, based on
      demonstrated reduction in risk for major cardiovascular events, its safety,
      acceptance by patients, and low cost.

PMID- 8268899
TI  - MRC trial of treatment in elderly hypertensives.
AB  - The MRC trial was a random control comparison of placebo treatment with two
      active drug regimens: atenolol 50 mg daily and a combined tablet containing
      hydrochlorothiazide 25 mg and amiloride 2.5 mg. The trial was based on 226
      general practices in the U.K. Its primary purpose was to determine whether
      hypotensive drug treatment in men and women aged 65-74 with systolic pressure in
      the range 160-209 mmHg and with diastolic pressure below 115 mmHg reduced stroke,
      coronary heart disease (CHD) and all-cause mortality. A secondary objective was
      to determine whether outcome differed with the two forms of active treatment.
      4,396 patients were randomized: 50% to placebo; 25% each to the two forms of
      treatment. During the following 5.8 years 25,000 patient-years of experience
      accumulated. Blood pressure fell in the placebo group, larger falls occurred with
      the two active treatments. Active treatment (diuretic and beta-blocker groups
      combined) reduced stroke by 25% (95% CI 3 to 42%), CHD by 19% (-2% to 36%, p =
      0.08), cardiovascular events by 17% (2% to 29%). Benefits were clearest for the
      diuretic regime: a 31% reduction of stroke events, a 44% reduction of CHD and a
      35% reduction of cardiovascular events--all significant.

PMID- 8268900
TI  - Antihypertensive therapy in elderly patients with isolated systolic hypertension:
      third progress report of the Syst-Eur trial.
AB  - The Syst-Eur trial is a randomised, double-blind, placebo-controlled trial that
      examines the hypothesis that antihypertensive treatment can prevent or delay
      cardiovascular complications in elderly patients (> 60 years) with isolated
      systolic hypertension. On March, 1st 1993 a total of 1395 patients with a sitting
      systolic blood pressure on placebo averaging 160-219 mmHg and a diastolic blood
      pressure < 95 mmHg were randomised into this trial. The placebo and active
      treatment groups were similar at randomisation with respect to age (72 +/- 7
      years, mean +/- SD), percentage of women (68%), percentage of patients with
      cardiovascular complications (30%) and sitting blood pressures (175 +/- 12/85 +/-
      6 mmHg). The fall in sitting systolic and diastolic blood pressures from baseline
      to 2 years was significantly more pronounced (p < 0.001) in the actively treated
      (-22 +/- 18/-6 +/- 9 mmHg) as compared with the placebo treated Syst-Eur patients
      (-10 +/- 20/-1 +/- 9 mmHg). Active treatment consists of nitrendipine if
      necessary associated with a converting-enzyme inhibitor and a thiazide. Whether
      treatment with these antihypertensive agents results in a clinically meaningful
      reduction of cardiovascular morbidity and mortality is the subject of
      investigation in this trial.

PMID- 8268901
TI  - The effects of blood pressure reduction in older patients: an overview of five
      randomized controlled trials in elderly hypertensives.
AB  - Direct evidence about the effects of antihypertensive treatment on vascular
      disease in older patients is available from five randomized trials conducted
      exclusively in patients over the age of 60 years. These trials involved a total
      of 12,483 individuals with systolic or diastolic hypertension (mean age = 72
      years, mean entry blood pressure = 181/88 mmHg). Over an average follow-up period
      of 4.7 years, a 15/6 mmHg difference in blood pressure between study and control
      groups was achieved. Among those patients assigned active treatment, stroke
      incidence was reduced by 34% SD6 and coronary heart disease incidence was reduced
      by 19% SD7. These proportional reductions were of similar size to those observed
      in trials in predominantly younger patients. However, the absolute benefits
      observed in older patients were more than twice as great as those observed in
      younger patients. The results suggest that over 10 years, treatment would prevent
      at least one major vascular event among every 10 elderly patients at similar risk
      to those enrolled in the trials.

PMID- 8268902
TI  - Prevalence of complications and response to different treatments of hypertension
      in African Americans and white Americans in the U.S..
AB  - The aim of this review is to compare the prevalence of complications and response
      to different treatment for hypertension in African and European Americans.
      African Americans when compared to European Americans respond less favorably to
      beta-blockers (BB's) and angiotensin converting enzyme inhibitors (ACEI's).
      Nevertheless the observed response of African Americans to ACEI's and BB's is
      significant and these agents are very effective in this subgroup. African
      American race is not a clinically significant predictor of poor response to any
      class of antihypertensive therapy and there is little justification to use racial
      profiling as a criterion for choice of medication. Evidence to restrict or defer
      usage of BB's and ACEI's in African Americans is lacking. The mortality from
      hypertensive heart disease, stroke, and the incidence of hypertensive renal
      disease is higher in African Americans which leads some investigators to
      postulate that hypertension in African Americans is intrinsically different from
      whites. They therefore search for a separate etiology and suggest specific
      approaches to treatment. Awareness of racial differences in hypertension outcomes
      evolved in the U.S. in an historical context that does not fully appreciate that
      race is often a surrogate for many social and economic factors that influence
      health status and health care delivery in the U.S. Poor outcomes in African
      Americans occur in many diseases including hypertension.

PMID- 8268903
TI  - Hypertension in Africa and effectiveness of its management with various classes
      of antihypertensive drugs and in different socio-economic and cultural
      environments.
AB  - Hypertension is the commonest cardiovascular disease in Africans occurring in
      more than 15% of the adult population in some studies. It occurs in the lower as
      much as in the higher socio-economic groups. Recent studies have confirmed
      earlier findings that essential hypertension in Africans is characterised by
      volume loading, low plasma renin activity, high salt taste threshold, high
      urinary sodium and low potassium excretion and high plasma aldosterone. The
      commonest complication of hypertension in Africans is congestive cardiac failure
      followed by cerebrovascular accidents. Coronary heart disease is rare. Even in
      the absence of overt heart failure and compounding factors like obesity,
      alcoholism, cigarette smoking, diabetes mellitus and myocarditis, evidence of
      abnormal left ventricular morphology and function is often present in newly
      diagnosed patients with moderate or severe hypertension. Response to monotherapy
      with beta-blockers or ACE inhibitors is usually poor but is good with thiazide
      diuretics or calcium channel blockers. The diuretics are an essential component
      of a two or three drug regime containing other classes of antihypertensive drugs.
      Cost of drugs is the most important determinant of compliance with drug treatment
      and consequently the likelihood of progression of the diseases to more severe
      forms in long term follow-up.

PMID- 8268904
TI  - The inv(16) in acute nonlymphocytic leukemia: a turnabout for myosin heavy chain.

PMID- 8268905
TI  - Cloning the breakpoint cluster region of the inv(16) in acute nonlymphocytic
      leukemia M4 Eo.
AB  - The pericentric inversion of chromosome 16 and the t(16;16) are two recurrent
      aberrations in bone marrow of patients with acute nonlymphocytic leukemia subtype
      M4 Eo, characterized by abnormal eosinophilic granulation. We describe here the
      precise localization of the breakpoints using fluorescence in situ hybridization
      (FISH) with cosmids spread over the short arm of chromosome 16 and the detection,
      isolation and characterization of a 14Kb EcoRI fragment containing a cluster of
      breakpoints. First, cosmids were mapped to intervals defined by constitutional
      16p rearrangements, second, the inv(16) and t(16;16) breakpoints were mapped to
      one of the intervals using FISH with the mapped cosmids and third, cosmids within
      this interval were ordered using two color interphase FISH. An STS of the cosmid
      closest to the breakpoints was then used to isolate five YACs, which did span all
      of the 16 inv(16) breakpoints and one t(16;16) breakpoint analysed. In the DNA of
      one inv(16) patient we detected an additional submicroscopic deletion immediately
      proximal to the 16p breakpoint. Since this patient has the same phenotype, the
      16p sequences proximal to the breakpoint seem non-essential to M4 Eo. This
      implies that the pathologic event is the juxtaposition of sequences distal to the
      16p breakpoint with sequences proximal to the 16q breakpoint. While four of the
      five YACs showed instability of the region around the inv(16) breakpoint, DNA
      halo analysis allowed us to identify one YAC which was co-linear with normal
      genomic DNA and has yielded the actual breakpoint sequences which could be
      subcloned into cosmids and fosmids.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268906
TI  - Molecular analysis of juvenile Huntington disease: the major influence on (CAG)n
      repeat length is the sex of the affected parent.
AB  - Juvenile Huntington disease (HD), characterised by onset of symptoms before the
      age of 20 with rigidity and intellectual decline, is associated with a
      predominance of affected fathers. In order to investigate the molecular basis for
      the observed parental effect, we have analysed the CAG trinucleotide repeat
      within the HD gene in 42 juvenile onset cases from 34 families. A highly
      significant correlation was found between the repeat length and age of onset (r =
      -0.86, p < 10(-7) and it was determined that the sex of transmitting parent was
      the major influence on CAG expansion leading to earlier onset. Neither the size
      of the parental upper allele, the age of parent at conception of juvenile onset
      child, nor the grandparental sex conferred a significant effect upon expansion.
      Affected sib pair analysis of CAG repeat length, however, revealed a high
      correlation (r = 0.91, p < 10(-7). Furthermore, analysis of nuclear and extended
      families showed a familial predisposition to juvenile onset disease. This study
      demonstrates that the sex of transmitting parent is the major influence on
      trinucleotide expansion and clinical features in juvenile Huntington disease.

PMID- 8268907
TI  - Correlation between the onset age of Huntington's disease and length of the
      trinucleotide repeat in IT-15.
AB  - Huntington's disease (HD) is an autosomal dominant disorder with a variable age
      of onset that is influenced by the sex of the affected parent. The recent
      recognition that HD is caused by an expanded triplet repeat suggests the
      possibility that the onset age may be predicted by the length of the repeat. This
      hypothesis was tested by assaying the length of the repeat in 114 individuals who
      were clinically diagnosed with HD and had a known onset age. Every individual had
      an expanded allele. The range was from 36 to 82 repeats (mean = 48.4 +/- 9.51)
      and larger than the normal range (6 to 31). The size of the expanded allele was
      correlated with the age of onset (r = -0.65 p < .0001). Despite the highly
      significant correlation, the repeat size explains less than half of the variance
      in onset age. Furthermore, the age of onset cannot be predicted from the size of
      the triplet repeat, particularly if the number of repeats is in the smaller end
      of the expanded range. If the repeat is < or = 50 triplets, the amount of
      variation in the age of onset explained by the length of the triplet repeat is
      less than 10%. As an illustration, the onset age of individuals with 39 repeats
      ranges from 30 to 65 years old. The sex of the affected parent had no effect in
      our sample beyond the effect of the length of the repeat. Affected offspring of
      affected fathers had longer repeats and a larger variance in allele size than
      offspring of affected mothers, perhaps reflecting greater instability in paternal
      transmission.

PMID- 8268908
TI  - A zinc-finger gene ZNF141 mapping at 4p16.3/D4S90 is a candidate gene for the
      Wolf-Hirschhorn (4p-) syndrome.
AB  - Chromosomal aneusomy is a major cause of reproductive wastage and congenital
      malformations in man. Zinc finger encoding genes would be good candidates for
      being involved in the multiple developmental defects associated with chromosomal
      aneusomy--by virtue of their role as transcriptional regulators, their abundance
      in the genome and their known association with specific developmental disorders.
      We have isolated and mapped a zinc finger encoding cDNA (ZNF141) of the C2
      H2/KRAB subfamily to the 4p- (Wolf-Hirschhorn) syndrome (WHS) chromosome region.
      ZNF141 mapped to the distal end of the 2.2 Mb smallest region of deletion overlap
      of WHS, 300 kb from the 4p telomere on cosmid CD1 defining the anonymous locus
      D4S90. ZNF141 was expressed ubiquitously at low levels in the analysed tissue.
      The identification of a candidate gene for a chromosomal aneusomy syndrome
      belonging to a class of evolutionary conserved genes will provide options for
      studying its normal and abnormal expression during mammalian embryogenesis.

PMID- 8268909
TI  - Isolation of a gene expressed during early embryogenesis from the region of 22q11
      commonly deleted in DiGeorge syndrome.
AB  - DiGeorge syndrome (DGS) is one of several syndromes associated with deletions
      within the proximal long-arm of chromosome 22. The region of chromosome 22q11
      responsible for the haploinsufficiency syndromes (the DiGeorge Critical Region or
      DGCR) has been mapped using RFLPs, quantitative Southern blotting and FISH.
      Similar deletions are seen in the velo-cardio-facial syndrome (VCFS) and familial
      congenital heart defects. It is not known whether the phenotypic spectrum is the
      result of the hemizygosity of one gene or whether it is a consequence of
      contiguous genes being deleted. However, the majority of patients have a large (>
      = 2Mb deletion). In this paper we report the isolation of a gene, lab name T10,
      encoding a serine/threonine rich protein of unknown function which maps to the
      commonly deleted region of chromosome 22q11. Studies in the mouse indicate that
      it maps to MMU16 and is expressed during early embryogenesis. Although not
      mapping within the shortest region of overlap for DGS/VCFS, and therefore not the
      major gene involved in DGS, the expression pattern suggests that this gene may be
      involved in modifying the haploinsufficient phenotype of hemizygous patients.

PMID- 8268910
TI  - Isolation of a zinc finger gene consistently deleted in DiGeorge syndrome.
AB  - DiGeorge syndrome is a human developmental disorder resulting in hypoplasia of
      the thymus and parathyroids, and conotruncal heart defects. We recently isolated
      four genes with zinc finger DNA binding motifs mapping to chromosome 22q11.2
      DiGeorge critical region. We now report that one of them, ZNF74 gene, is
      hemizygously deleted in 23 out of 24 DiGeorge syndrome patients tested. ZNF74
      mRNA transcripts are detected in human and mouse embryos but not in adult
      tissues. Sequence analysis of a corresponding cDNA reveals an an open reading
      frame encoding 12 zinc finger motifs of the Kruppel/TFIIIA type as well as N
      terminal and C-terminal non-zinc finger domains. These results suggest that
      changes in the dosage of a putative transcription factor through ZNF74 hemizygous
      deletion may be critical for DiGeorge developmental anomalies.

PMID- 8268911
TI  - A tight cluster of five unrelated human genes on chromosome 16q22.1.
AB  - A locus on human chromosome 16q22.1 contains at least five tightly clustered
      genes which are unrelated by sequence homology and apparently unrelated by
      function. The genes for a putative proteasome subunit (MECL 1), a chymotrypsin
      like protease (CTRL), a protein serine kinase (PSKH1), the previously cloned
      lecithin:cholesterol acyl transferase (LCAT) and a protein of unknown function
      are found within 40 kb of genomic DNA. Exons from the former four genes are
      located within a 12 kb region including a CpG island associated with the putative
      proteasome gene. Three of the genes are widely expressed, whereas the genes for
      the protease and LCAT are highly tissue specific. The distance between the
      transcriptional units of the gene upstream of LCAT and LCAT is only 199 bp.
      Alternative polyadenylation of the protease transcripts creates a transcription
      unit which overlaps with the oppositely oriented kinase gene. The selective
      advantage of this unusual gene clustering may involve transcriptional
      interference(s) and coregulatory events not yet understood. Given the current
      estimate of about 100,000 genes in the human genome, our findings support the
      notion that genes are not evenly distributed.

PMID- 8268912
TI  - Characterization and chromosomal localization of the human proto-oncogene BMI-1.
AB  - The proto-oncogene bmi-1 is frequently activated by Moloney murine leukemia
      proviral insertions in E mu-myc transgenic mice1,2. Using a mouse bmi-1 cDNA
      probe a transcript of 3.3 kb was detected on Northern blots of human Burkitt's
      lymphoma cell lines. We have isolated and sequenced cDNA clones from a human
      erythroleukemia cell line (K562) derived cDNA library, using different mouse bmi
      1 cDNA fragments as a probe. Analysis of genomic BMI-1 sequences reveals a gene
      structure which is very similar to that of the mouse, consisting of at least 10
      exons. The human cDNA is 3203 bp in length and shows 86% identity to the mouse
      nucleotide sequence. The open reading frame encodes a protein of 326 amino acids
      which shares 98% identity to the amino acid sequence of mouse bmi-1 protein. In
      vitro translation experiments show that human cDNA derived RNA translates into a
      protein with a mobility of 44-46 kD on SDS polyacrylamide gels. Fluorescence in
      situ hybridization (FISH) on metaphase chromosome spreads located the human BMI-1
      gene to the short arm of chromosome 10 (10p13), a region known to be involved in
      translocations in various leukemias.

PMID- 8268913
TI  - Duplicated zinc finger protein genes on the proximal short arm of the human X
      chromosome: isolation, characterization and X-inactivation studies.
AB  - Two highly similar zinc finger genes, ZXDA (Zinc finger, X-linked, Duplicated)
      and ZXDB, have been isolated and characterized. Both map to the proximal short
      arm region of the human X chromosome, near locus DXS422 in Xp11.21. Both genes
      are expressed in several human tissues, revealing a approximately 6.5 kb mRNA by
      Northern blot hybridization, and both are subject to X-inactivation. A comparison
      of 1.2 kb of cDNA sequence from a single exon in the open reading frames of the
      two genes reveals 98.7% identity in nucleotide sequence. The predicted proteins
      include at least ten tandem C2-H2 zinc finger motifs. When cDNA probes from
      different parts of the genes are hybridized to a blot of different animal DNAs,
      two bands are seen in all placental mammals, suggesting that the duplication
      predates the radiation of placental mammals and is highly conserved. Furthermore,
      under conditions of lowered stringency, additional bands are seen in several
      species, suggesting that the two genes reported here may be members of a larger
      zinc finger gene family.

PMID- 8268914
TI  - Maternally transmitted partial direct tandem duplication of mitochondrial DNA
      associated with diabetes mellitus.
AB  - Mitochondrial DNA from a 38 year old male with diabetes mellitus and features of
      mitochondrial dysfunction was analysed and shown to include a population with a
      partial duplication. The partially duplicated mitochondrial DNA molecules were
      evident in both muscle and blood. The region of mitochondrial DNA duplicated
      includes the origin of heavy strand replication, but not the light strand origin.
      This patient has features in common with other cases of partial direct tandem
      duplications and with a family which was reported to harbour a 10.4 kb mtDNA
      deletion. Initial restriction enzyme analysis of our case produced results
      consistent with a partial deletion of mitochondrial DNA. This leads us to propose
      that the rarity of reports of partial mitochondrial DNA duplications may stem in
      part from the classification of such mutants as partial deletions.

PMID- 8268915
TI  - Linkage of a locus (CMT4A) for autosomal recessive Charcot-Marie-Tooth disease to
      chromosome 8q.
AB  - Autosomal recessive Charcot-Marie-Tooth (CMT) disease (CMT4) is a complex group
      of severe childhood motor and sensory neuropathies, characterized by an early age
      of onset with rapidly progressive distal limb weakness and atrophy. One subgroup
      designated CMT4 type A (CMT4A) was selected from a series of Tunisian CMT4
      families according to the following electrophysiological and pathological
      criteria: slow motor nerve conduction velocity (MCV), severe hypomyelination upon
      nerve biopsy with basal lamina onion bulbs and no myelin outfolding. In an
      attempt to localize the CMT4A locus, we studied four inbred families with 13
      affected patients. Significant evidence for linkage was found for several markers
      from chromosome 8q13-21.1 (D8S279, D8S164, D8S286, D8S84, D8S275 and D8S167). An
      overall two point peak lod score of z(theta) = 9.19 at theta = 0.00 (95%
      confidence limit 0.00-0.08) was obtained for D8S164. No evidence of genetic
      heterogeneity was found. The chromosomal localization of one form of CMT4 will
      have important implications in clarifying the nosology of this complex group of
      disorders.

PMID- 8268916
TI  - Four-state MVR-PCR: increased discrimination of digital DNA typing by
      simultaneous analysis of two polymorphic sites within minisatellite variant
      repeats at D1S8.
AB  - Minisatellite variant repeat mapping by PCR (MVR-PCR) provides a digital approach
      to DNA typing that can reveal huge levels of variation at minisatellite loci. MVR
      PCR has so far been applied to three human minisatellites, including the
      hypervariable locus D1S8. Previous analysis at D1S8 was based on the
      discrimination of repeat unit types that differ by a single base substitution. We
      now show that a second polymorphic site within D1S8 repeats may be assayed
      simultaneously with the first to define four classes of repeat units ('four-state
      MVR-PCR'). This approach can also be applied to the other end of D1S8 alleles in
      'reverse four-state MVR-PCR'. Both of these procedures substantially increase the
      informativeness of MVR analysis at D1S8 and should prove useful in studies of
      minisatellite biology and potentially in forensic DNA typing.

PMID- 8268917
TI  - Long-range analyses of the centromeric regions of human chromosomes 13, 14 and
      21: identification of a narrow domain containing two key centromeric DNA
      elements.
AB  - Alpha-satellite, satellite 3 and satellite 1 DNA have been proposed as candidate
      components of a functional human centromere. Multiple subfamilies of these three
      DNA have recently been identified at the pericentric regions of the human
      acrocentric chromosomes. Using pulsed field gel electrophoresis, we have
      constructed long-range maps of the various centromeric markers for chromosomes
      13, 14 and 21. These maps cover approximately 2.3 megabases of sequence for each
      chromosome, and the results demonstrate that within this centromeric region,
      chromosomes 13 and 21 have a similar organization that is partially shared by
      chromosome 14. A discrete satellite 3 domain was identified on each chromosome
      within the boundaries of the alpha-satellite DNA. No satellite 1 was detected
      within the defined centromeric regions suggesting that satellite 1 is not
      essential for centromere function.

PMID- 8268918
TI  - Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue
      specific isoforms and chromosomal localization.
AB  - Dystroglycan is a novel laminin binding component of the dystrophin-glycoprotein
      complex which provides a linkage between the subsarcolemmal cytoskeleton and the
      extracellular matrix. Here we report the cDNA and genomic structure of human
      dystroglycan. The human dystroglycan is encoded by a single gene (DAG1) mapped to
      chromosome 3 band p21. The coding sequence is organized into two exons, separated
      by a large intron. The predicted amino acid sequence of human and rabbit
      dystroglycan are 93% identical with predicted glycosylation sites being
      conserved. Human dystroglycan is expressed in a variety of fetal and adult
      tissues. Our data suggest that muscle and non-muscle isoforms of dystroglycan
      differ by carbohydrate moieties but not protein sequence. Therefore, we
      hypothesize that variable glycosylation of the conserved protein core might
      modulate laminin binding. The relationship of dystroglycan to human diseases is
      discussed.

PMID- 8268919
TI  - High resolution methylation analysis of the FMR1 gene trinucleotide repeat region
      in fragile X syndrome.
AB  - Fragile X syndrome is the most common form of inherited mental retardation in
      man. The disease is associated with expansion in the number of tandem CGG
      trinucleotide repeats in the 5' untranslated region of the human FMR1 gene.
      Transmitting males, individuals who are unaffected carriers of the disease, show
      a moderate increase in the number of repeat units, while fully penetrant males
      show a major expansion in repeat number. Major expansion of the repeat in
      affected males is correlated with methylation of certain restriction enzyme
      recognition sites in the 5' CpG island containing the trinucleotide repeat in
      these patients. Phenotypic expression of the mutation appears to be due to
      transcriptional silencing of the FMR1 gene. We now report direct high resolution
      methylation analysis of the trinucleotide repeat and its flanking regions using
      ligation-mediated PCR genomic sequencing. We find the cytosine residue of all CpG
      dinucleotides examined within and surrounding the FMR1 trinucleotide repeat to be
      unmethylated in the DNA of normal male leukocytes and transmitting male
      lymphoblasts; these same cytosines are methylated in affected male lymphoblasts,
      in a somatic cell hybrid containing a fragile X chromosome from an affected male,
      and in a somatic cell hybrid containing a normal inactive X chromosome. The
      methylation pattern of the FMR1 5' CpG island in affected patients as determined
      by genomic sequencing is remarkably similar to that seen for the X-linked human
      phosphoglycerate kinase and hypoxanthine phosphoribosyltransferase gene 5' CpG
      islands on the inactive human X chromosome.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268920
TI  - Physical mapping and YAC-cloning connects four genetically distinct 4qter loci
      (D4S163, D4S139, D4F35S1 and D4F104S1) in the FSHD gene-region.
AB  - We have constructed a long-range restriction map of the region on chromosome 4q
      that contains the gene for facioscapulohumeral muscular dystrophy (FSHD). This
      region contains the linkage group cen ... D4S163-D4S139-D4F35S1-D4F104S1-FSHD ...
      4qter, which spans a genetic distance of about 5 cM. Pulse field gel
      electrophoresis (PFGE) mapping indicated that these loci span a region not more
      than 1 Mb. STSs were developed for several of these loci, which served to isolate
      four overlapping yeast artificial chromosomes (YACs). These YACs confirmed the
      PFGE map and have allowed us to generate a more detailed restriction map using
      cosmid contig mapping. The physical distances were smaller than was expected on
      the basis of the genetic map. Two potential HTF islands have been detected within
      the cloned region. One HTF island maps about 100 kb centromeric from the tandem
      repeats involved in the FSHD mutation, whereas the other maps within these tandem
      repeats.

PMID- 8268921
TI  - Characterisation of molecular DNA rearrangements within the Xq12-q13.1 region, in
      three patients with X-linked hypohidrotic ectodermal dysplasia (EDA).
AB  - A panel of somatic cell hybrids and X-linked hypohidrotic ectodermal dysplasia
      (EDA) patient-derived cell lines, containing different rearranged X chromosomes,
      have been used to refine the physical map of the Xq12-q13.1 region. The patient
      derived material included genomic DNA from an EDA male (EDA family 1015) with an
      interstitial deletion, and a cell line GM0705A, obtained from an isolated female
      patient with a de novo balanced (X;9) translocation, and the somatic hybrid,
      AnLy, derived from this cell line. This map subdivides the region into at least 6
      mapping-intervals. DNA probes from DXS732 and DXS453, identified as the closest
      flanking marker loci to the EDA locus, were used to identify homologous Yeast
      Artificial Chromosome (YAC) clones. Two of the DXS732-specific YACs were shown by
      fluorescent in situ hybridisation (FISH) analysis to bridge the (X;9)
      translocation breakpoint. These two YACs were also screened against the ICRF
      human X chromosome cosmid library and identified 36 cosmid clones. Direct cosmid
      cosmid hybridisation analysis placed subsets of these clones within four
      different cosmid contigs. Mapping of anchor clones from each contig, against the
      mapping panel, localised all these contigs within the Xq12-q13.1 region. One
      cosmid, ICRFc104C03.184, identified potential junctional-fragments in several
      restriction digests of AnLy hybrid DNA. This was confirmed by FISH analysis of
      the GM0705A cell line with total cosmid ICRFc104C03.184, in which both
      chromosomal elements of the (X;9) translocation were identified. A single-copy
      probe pC03.184E2, derived from this cosmid, also identified the der(9)-derived
      junctional fragment when hybridised against AnLy DNA.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268922
TI  - Timing of p53 mutations during astrocytoma tumorigenesis.
AB  - Using a combination of polymerase chain reaction and single-strand conformation
      polymorphism techniques (PCR-SSCP) we have analyzed 78 brain tumor samples (70
      primary and 8 metastatic) for the presence of mutations in the conserved regions
      of the Tp53 (tumor p53) gene. We have found that only two groups, gliomas
      (exclusively in astrocytomas) and metastases, displayed Tp53 mutations. Three of
      eight (37.5%) metastases showed a mutant Tp53 allele accompanied by loss of the
      normal one. In contrast, the frequency of Tp53 mutations in the primary brain
      tumors examined was lower (5.7%). Although we have examined different types of
      primary brain tumors, Tp53 mutations were exclusively observed in both, low and
      high-grade astrocytomas (four of 24). The Tp53 mutations detected in astrocytic
      tumors appear to be correlated with the malignancy grade. The low-grade
      astrocytomas were heterozygous for the mutation, whereas the high-grade
      astrocytomas had affected the two Tp53 alleles, suggesting a two-steps model for
      inactivation of the p53 gene in astrocytomas. Thus, single p53 mutation seems to
      occur in initial stages of astrocytoma tumorigenesis; the later lost of the
      remaining wild-type allele appears associated with the progression towards a more
      malignant stage.

PMID- 8268923
TI  - Paternal nondisjunction in trisomy 21: excess of male patients.
AB  - Paternal nondisjunction accounts for approximately 5% of cases of trisomy 21. We
      have studied 36 cases of free trisomy 21, in which the supernumerary chromosome
      was of paternal origin, with DNA markers in the pericentromeric region and along
      the long arm of chromosome 21. Fifteen of the paternal cases were consistent with
      meiosis II errors, 8 with mitotic errors and only 7 with meiosis I
      nondisjunction. This contrasts markedly with maternally derived trisomy 21, in
      which meiosis I errors predominate. An excess of males was observed in the
      meiotic cases (21 males:6 females), highly significantly different from a 1.06
      ratio. A significant difference in mean maternal age was found between cases of
      paternal origin (28.1 years) and those of maternal origin (31.8 years, n = 429).
      This indicates that the maternal age effect is confined to maternal
      nondisjunction.

PMID- 8268924
TI  - Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory
      sequence in the human LINE-1 transposable element.
AB  - The first step of the currently favored model for the mechanism of transposition
      of the human LINE-1 element involves the synthesis of full length LINE-1 mRNA.
      Previous work demonstrated that the 5'-terminal 100 base pairs of the human LINE
      1 element (L1Hs) has an important role in regulating it's expression. Here we
      report further deletion analysis revealing the presence of a cis regulatory
      element overlapping the region between base pairs +12 and +18. Oligonucleotides
      containing this sequence form a specific complex with a nuclear protein extracted
      from NTera2D1 and Jurkat cells, and with recombinant YY1 produced in E. coli. The
      complex is competed by YY1 binding sites found in other genes, and is ablated by
      anti-YY1 serum. These results suggest that YY1 is involved in the regulation of
      L1Hs transcription and therefore transposition.

PMID- 8268925
TI  - Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily:
      implications for diagnosis of hyperphenylalaninemia in southern Europe.
AB  - Hyperphenylalaninemia due to a deficiency of hepatic phenylalanine hydroxylase
      (PAH) is the most common inborn error of amino acid metabolism. Clinically, the
      disorder is highly heterogeneous, spanning from nonphenylketonuria
      hyperphenylalaninemia to classical phenylketonuria. Only little is known about
      the molecular defects underlying hyperphenylalaninemia in Southern Europe. In
      this study, we conducted a systematic analysis of 53 patients from the Sicilian
      population. Each patient included in the study had persistently elevated blood
      levels of phenylalanine and met the differential criteria for PAH deficiency.
      Genomic DNA was analysed by scanning all PAH-coding exons for mutations by PCR in
      combination with denaturing gradient gel electrophoresis (DGGE). 52 patients were
      completely genotyped. A spectrum of 40 different mutations was established
      including 17 novel PAH mutations. Our results explain the clinical heterogeneity
      of hyperphenylalaninemia in Southern Europe, and form the basis for the
      establishment of phenotype-genotype correlations in Sicily and surrounding
      countries.

PMID- 8268926
TI  - Characterization of a single base-pair deletion in neurofibromatosis type 1.
AB  - The gene which is responsible for neurofibromatosis type 1 (NF1) is located on
      chromosome 17 (17q11.2). The NF1 gene is approximately 350 kilobases (kb) long
      and exhibits an extremely high mutation rate; therefore, most patients are
      expected to have unique mutations. To date, relatively few mutations have been
      well characterized. We report here a de novo single base pair (bp) deletion in
      one NF1 allele in a patient diagnosed with NF1 and leukemia. We further
      characterized this mutation at the RNA level by allele-specific oligonucleotide
      (ASO) hybridization which demonstrated that the mutant allele is transcribed.

PMID- 8268927
TI  - Analysis of the huntingtin gene reveals a trinucleotide-length polymorphism in
      the region of the gene that contains two CCG-rich stretches and a correlation
      between decreased age of onset of Huntington's disease and CAG repeat number.

PMID- 8268929
TI  - Protein truncation test (PTT) for rapid detection of translation-terminating
      mutations.
AB  - Currently available techniques used to recognize point mutations in genetic
      disease are time consuming and are capable of screening only small pieces of DNA.
      Moreover, they detect all sequence differences including phenotypically silent
      changes. Consequently, they are not convenient to analyse mutations in large,
      multi-exonic genes, where a large fraction of pathological point mutations arises
      from early termination, as is the case for the one third non-deletion/duplication
      cases of Duchenne Muscular Dystrophy. We have developed a rapid and sensitive
      method, the Protein Truncation Test (PTT). PTT is based on a combination of RT
      PCR, transcription and translation and selectively detects translation
      terminating mutations. We demonstrate its effectiveness to detect point mutations
      in DMD-patients and carrier females. PTT should be widely applicable
      diagnostically in any disease where early terminations contribute substantially
      to the disease cause.

PMID- 8268928
TI  - Translocation breakpoint in Aarskog syndrome maps to Xp11.21 between ALAS2 and
      DXS323.

PMID- 8268930
TI  - Detection of growth hormone gene deletions by PCR of the hGH-N gene in isolated
      growth hormone deficiency.

PMID- 8268931
TI  - Characterization of a mutation within the NDP gene in a family with a manifesting
      female carrier.

PMID- 8268932
TI  - Identification of a new missense mutation at Arg403, a CpG mutation hotspot, in
      exon 13 of the beta-myosin heavy chain gene in hypertrophic cardiomyopathy.

PMID- 8268933
TI  - Screening for polymorphism in the tyrosine-sulfated region of human C4.

PMID- 8268934
TI  - Two novel mutations of the porphobilinogen deaminase gene in acute intermittent
      porphyria.

PMID- 8268935
TI  - A novel point mutation (D380A) and a rare deletion (1255del55) in the
      glucocerebrosidase gene causing Gaucher's disease.

PMID- 8268936
TI  - Tetranucleotide repeat polymorphisms at the D8S342, D8S323, D8S345, D8S315 and
      D8S347 loci on 8q.

PMID- 8268937
TI  - Two dinucleotide repeat polymorphisms at 21q22.3 (D21S416 and D21S1235).

PMID- 8268938
TI  - Four dinucleotide repeat polymorphisms on human chromosome 16.

PMID- 8268939
TI  - A polymorphism in the coding region of the vasopressin type 2 receptor (AVPR2)
      gene.

PMID- 8268940
TI  - Dinucleotide repeat polymorphisms in the VHL region of human chromosome 3p25.

PMID- 8268941
TI  - Dinucleotide repeat polymorphism at the D18S365 locus.

PMID- 8268943
TI  - CAT repeat polymorphism in a human expressed sequence tag (EST00444) (D13S308).

PMID- 8268942
TI  - Dinucleotide repeat polymorphism at D11S994 locus.

PMID- 8268944
TI  - Dinucleotide repeat polymorphism in the interferon regulating factor 1 (IRF1)
      gene.

PMID- 8268945
TI  - A dinucleotide repeat polymorphism at the ribosomal protein S6 (RPS6) gene.

PMID- 8268946
TI  - Dinucleotide repeat polymorphism at the D22S351 locus.

PMID- 8268947
TI  - A novel sequence polymorphism in exon 1 of the human vitamin D-binding protein
      (GC) gene.

PMID- 8268948
TI  - Dinucleotide repeat polymorphism at the D14S294 locus.

PMID- 8268949
TI  - Population variation in the dinucleotide repeat polymorphism at the D8S360 locus.

PMID- 8268950
TI  - A (CA)n repeat polymorphism at the 5' end of the alpha 1-antitrypsin gene (PI).

PMID- 8268951
TI  - A (CA)n repeat polymorphism in the protein C inhibitor (PCI) gene.

PMID- 8268952
TI  - Amino acid dimorphism in IL1A is detectable by PCR amplification.

PMID- 8268953
TI  - Dinucleotide repeat polymorphism proximal to the spinal muscular atrophy region
      at D5S681.

PMID- 8268954
TI  - Dinucleotide repeat polymorphism at the D12S371 locus.

PMID- 8268955
TI  - Dinucleotide repeat polymorphism at the D5S214 locus.

PMID- 8268956
TI  - An STR polymorphism at the CYBB locus.

PMID- 8268957
TI  - New human DNA polymorphisms submitted to the genome data base.

PMID- 8268958
TI  - Genomic organization of the sequence coding for fibrillin, the defective gene
      product in Marfan syndrome.

PMID- 8268959
TI  - Lumbosacral dysfunctions in elite cross-country skiers.
AB  - While the incidence of injury in cross-country skiing remains relatively low,
      overuse problems affecting the lumbosacral region may be on the rise,
      particularly among elite athletes. In this study, a certified "Part A" (Canadian
      Physiotherapy Association) manual therapist performed lumbosacral physical
      assessments on 18 elite cross-country skiers and 15 normal subjects. Results
      indicated sacroiliac (SI) joint dysfunction occurred significantly more often in
      the skier population (p < 0.007). Incidences of SI joint asymmetry and lumbar
      spine dysfunction did not differ between groups. The predominant use of
      asymmetrical ski-skating techniques may play an influential role in the
      pathogenesis of SI joint dysfunction in elite cross-country skiers.

PMID- 8268960
TI  - Muscle function in chronic compartment syndrome of the leg.
AB  - Chronic compartment syndrome (CCS) is a recognized cause of recurrent leg pain in
      the exercising patient. Decreased muscle function has been implied in this
      condition. This study compared the ankle dorsiflexion torque of 10 CCS patients
      with that of 18 control subjects during 20 repeated, maximal, isokinetic
      contractions at 60 degrees/sec. Peak torque, relative peak torque, and endurance
      data were collected. Results showed significantly lower peak torque and relative
      peak torque in the CCS group (p < or = 0.05), supporting the implication of
      muscle weakness in CCS. Paradoxically, endurance was significantly higher in the
      CCS group (p < or = 0.01), and there was a significant (p < or = 0.01), negative
      correlation (r = -0.50) between peak torque and endurance. The relationship
      between the findings and CCS is discussed. Strengthening may be useful in very
      mild cases or in postfasciotomy patients.

PMID- 8268961
TI  - The effects of phonophoresis with corticosteroids: a controlled pilot study.
AB  - Although physical therapists and physicians often treat patients with local
      musculoskeletal inflammation using topically applied steroids enhanced with
      ultrasound, there is a paucity of research confirming that phonophoresis
      significantly enhances drug diffusion. The purpose of this study was to determine
      if ultrasound enhances the diffusion of transdermally applied corticosteroids.
      Diffusion was measured secondarily in terms of collagen deposition [estimated by
      levels of hydroxyproline in polytetrafluroethylene (ePTFE) tubing] and cellular
      activity (measured by levels of DNA). Sixteen pieces of ePTFE tubing were
      subcutaneously implanted on the dorsum of five mini Yucatan pigs. Pairs of tubing
      were randomly assigned to sham control or treatment groups. Over the paired ePTFE
      tubes in the treatment groups, a single transdermal application of hydrocortisone
      acetate (HC) or dexamethasone (DX) was applied to the skin by rubbing, sonating
      with the drug mixed in the acoustic gel (1.5 W/cm2, 1 MHz, 5 minutes), or
      injecting the drug into the tubing. Four additional ePTFE tubes were threaded in
      the extremities, two submuscularly and two subtendinously, with random assignment
      to a sham control or a DX sonation treatment group. At the end of a week, the
      mean hydroxyproline levels in the swine were lower than expected (mean = 9.3
      micrograms/cm compared to an expected mean = 22.2 micrograms/cm). Comparing the
      control and skin-applied groups with the injected and sonated treatment groups,
      the hydroxyproline was found to be 50% lower in the DX-injected, DX-sonated, and
      HC-injected sites. However, statistically there were no significant differences
      in DNA or hydroxyproline levels between the HC subcutaneous control and treatment
      groups or the DX submuscular and subtendinous groups. There was a significant
      main effect of group on hydroxyproline levels in the group of DX-treated,
      subcutaneously implanted ePTFE tubes (p = 0.001). Post hoc testing revealed a
      significant difference between the skin-rubbed and control groups together
      compared to the DX-injected and DX-sonated groups together (p = 0.001). These
      findings indicate that the effects of phonophoresed DX can be measured in terms
      of reduced collagen deposition as far down as the subcutaneous tissue but not in
      the submuscular or subtendinous tissue. However, a single application may not
      have a measurable effect on cellular activity after 7 days of healing. The
      unusually low level of hydroxyproline across all groups suggests that
      phonophoresis with steroids may have had a systemic as well as a local effect.

PMID- 8268962
TI  - The relative effectiveness of three forms of visual knowledge of results on peak
      torque output.
AB  - Therapists often search for more efficient and effective ways to provide patients
      with information regarding their performance. The purpose of this study was to
      determine whether certain types of machine-based visual displays could be used as
      a source of error-correction information to facilitate the immediate and/or
      delayed performance of a maximal effort isokinetic movement of the knee. The
      relative effectiveness of the knowledge of results (KR) provided by visual
      displays that differed in degree of precision and presentation schedule were
      compared during a practice and retention test phase. Twenty-four healthy male
      subjects (mean age = 22 years) performed isokinetic extension and flexion of the
      knee at low (120 degrees/sec) and high (240 degrees/sec) exercise speeds. A no-KR
      maximal effort pretest was followed by two practice sessions during which three
      groups each received one form of visual KR and a fourth group practiced without
      KR. A no-KR maximal effort posttest was administered to all groups following a 1
      day rest interval. Although visual KR did not result in any significant
      differences in mean peak torque output during practice, between-group comparisons
      of pretest to posttest changes in mean peak torque indicated that groups
      receiving visual KR in addition to practice demonstrated significantly greater (p
      < .03) improvements in mean peak torque in three of the four conditions tested
      when compared with the group that practiced without KR.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8268963
TI  - Intramachine and intermachine reliability for selected dynamic muscle performance
      tests.
AB  - The Cybex 6000 isokinetic dynamometer is a new isokinetic device for which no
      published reports of reliability have been presented in the literature. In
      addition, the manufacturer not only claims that the new Cybex 6000 is reliable
      but that torque data obtained from the Cybex 6000 are consistent with data
      obtained from past Cybex systems, such as the Cybex II. The purpose of this study
      was to investigate the intramachine reliability of the Cybex 6000 to itself and
      the intermachine reliability of the Cybex 6000 and the Cybex II. Data on peak
      torque, work, and power were collected using the Cybex 6000, and data on peak
      torque were obtained using the Cybex II for knee flexion and extension in 20
      volunteers (10 males, 10 females). Subjects were tested three times, twice on the
      Cybex 6000 and once on the Cybex II, approximately 1 week apart across a 3-week
      period of time at angular velocities of 60, 180, and 300 degrees/sec. Data were
      analyzed using intraclass correlations. Results indicated that the majority of
      test-retest correlation coefficients for all parameters for intramachine
      reliability of the Cybex 6000 were above .90. Comparing peak torque obtained with
      the Cybex 6000 to that obtained with the Cybex II (intermachine reliability),
      correlation coefficients ranged from .72 to .89. In conclusion, information
      obtained on the Cybex 6000 appears to be quite reliable in a test-retest
      situation using the same equipment and moderately reliable when compared to the
      Cybex II. Clinical implications for these results are discussed.

PMID- 8268964
TI  - Comparison of four clinical tests for assessing hamstring muscle length.
AB  - Several indirect clinical tests for measuring hamstring muscle length are
      available, but the influence of their test procedures is not well documented.
      This study examined four of these tests to clarify the results relative to the
      testing procedures. The right limbs of 30 men were tested for: 1) passive
      straight leg raise (SLR) with the pelvis and opposite thigh stabilized with
      straps (SLR-SS); 2) passive SLR with the low back flat and, if needed, the
      opposite thigh slightly flexed and supported on pillows (SLR-LBF); 3) active knee
      extension with the hip at 90 degrees (AKE); and 4) passive knee extension with
      the hip at 90 degrees (PKE). A dependent t-test showed no significant differences
      between the angles of SLR-SS (61 degrees +/- 6.7 degrees) and SLR-LBF (62 degrees
      +/- 6.2 degrees). The SLR-SS and SLR-LBF angles for subjects needing pillows
      under the opposite thigh for the SLR-LBF test (N = 18) also were not
      significantly different. The knee flexion angles for the AKE (43 degrees +/- 10.2
      degrees) and the PKE (31 degrees +/- 7.5 degrees) tests were significantly
      different (p < 0.001). Significant relationships (Pearson r) were found among the
      four tests (p < 0.05). The similar angles for SLR-SS and SLR-LBF and their
      significant relationship (r = 0.70, p < 0.001) indicated that their different
      testing procedures probably had a minimal influence on test results. The
      difference between the AKE and PKE tests suggested that the AKE test and the PKE
      test may represent an "initial length" and a "maximal length,"
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8268965
TI  - Incisional wound healing: a controlled study of low and high dose ultrasound.
AB  - Ultrasound is commonly used by physical therapists, but there is no consensus
      regarding the most effective therapeutic dose for accelerating healing of open or
      closed wounds. A controlled, single-blind, posttest experimental study was
      carried out to compare differences in wound breaking strength and collagen
      deposition [hydroxyproline (HoPro)]. Forty-eight incisions were surgically
      induced in three mini Yucatan pigs. Each incision was randomly assigned to a
      control or an ultrasound treatment group with the sonated incisions further
      randomly assigned to 5 or 10 days of ultrasound treatment with either high dose
      ultrasound (HUS) (1.5 W/cm2, continuous mode, 1 MHz, 5 minutes) or low dose
      ultrasound (LUS) (0.5 W/cm2, pulsed mode, 20% duty cycle, 1 MHz, 5 minutes).
      Using the nonparametric two-sample Wilcoxon test, the breaking strength was found
      to be significantly higher in the sonated incisions compared with the control
      incisions (p < or = 0.02), but there were no significant differences in HoPro.
      For all groups, the level of HoPro measured the second week was significantly
      higher (an average of 60%) than measured the first week (p < or = 0.001). A
      significant interaction was found between the number of days of treatment and the
      dose of ultrasound. Hydroxyproline was significantly higher in the LUS group
      compared with the HUS group after 5 days of ultrasound. Both the wound breaking
      strength and the HoPro levels were significantly higher in the LUS group compared
      with the HUS group after 10 days of treatment (p < or = 0.02 and 0.01,
      respectively). The findings from this study suggest that physical therapists can
      use either LUS or HUS for approximately 1 week to enhance wound breaking strength
      in an acute incisional wound. However, if the goal is to continue to facilitate
      collagen deposition and wound strength, then a low dose of ultrasound should be
      used when treatment is continued for 2 weeks or more.

PMID- 8268966
TI  - Chronic adductor tendinitis in a female swimmer.
AB  - Although hip and groin pathologies are not as prevalent as other lower extremity
      injuries, information on the course of physical therapy to remedy these injuries
      is needed. This case study reviews an episode of chronic adductor tendinitis and
      the subsequent course of treatment. A 16-year-old female swimmer developed
      symptoms of an adductor strain that failed to respond to varied conservative
      treatments over 1 year. A unilateral tenotomy was performed, and follow-up
      treatment was provided. Although this patient is not symptom-free, she is
      swimming competitively at a major Division I college. Consideration of more than
      one causative factor and aggressive early diagnosis must be performed to prevent
      groin pain from becoming chronic.

PMID- 8268967
TI  - Immunopathology of Sjogren's syndrome: more questions than answers.

PMID- 8268968
TI  - Role of transforming growth factor beta (TGF beta) in systemic autoimmunity.
AB  - Transforming growth factor (TGF beta) is a multifunctional cytokine with
      proinflammatory as well as immunosuppressive activities. A regulatory role for
      TGF beta has been suggested in investigations of several experimental and
      spontaneous models of pathological autoreactivity. It is suggested that many of
      the functional effects of TGF beta parallel the major immune system abnormalities
      seen in SLE.

PMID- 8268969
TI  - Effects of an aromatase inhibitor on thymus and kidney and on oestrogen receptors
      in female MRL/MP-lpr/lpr mice.
AB  - The effects of an aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA), which
      blocks oestrogen formation, have been studied in female MRL/MP-lpr/lpr mice which
      are a model of SLE. At 11.5 weeks, mice were implanted subcutaneously either with
      empty Silastic implants or with implants containing 25 mg 4-OHA. At 15 weeks,
      they were sacrificed by decapitation and liver, thymus, kidneys and uterus taken
      for wet weight, histology and measurement of cytosolic and nuclear oestrogen
      receptors. Thymus weights were significantly lower in 4-OHA-treated mice although
      uterus weights were similar in both groups. Also, whereas thymuses from control
      treated mice were packed with plasma cells with abundant cytoplasm, those from 4
      OHA-treated mice contained T cells with large nuclei. Relative oestrogen receptor
      abundances were: uterus > liver > thymus, although cytosolic receptors could not
      be detected in thymus cytosols of MRL mice unless they were treated with the
      aromatase inhibitor. In kidney, there was histological evidence that inflammation
      was limited to mesangium in 4-OHA-treated mice. These results support the
      hypothesis that oestrogens may be involved in the aetiology of murine SLE and
      provide data suggesting that substances which block oestrogen production in vivo
      may be useful to treat certain forms of SLE.

PMID- 8268970
TI  - Lymphocyte subsets in a large cohort of patients with systemic lupus
      erythematosus.
AB  - In search of markers of disease activity in patients with SLE we have
      investigated blood lymphocyte subsets from a large cohort of patient. Seventy-one
      patients were studied using a well-defined panel of fluorescent monoclonal
      antibodies which recognize the major T, B and NK lymphocyte subsets and activated
      cells. Flow cytometry was used with standard automated software. Overall, SLE
      patients were lymphopenic. The proportion of activated T cells was increased and
      NK cells were decreased in both proportion and absolute numbers (P < 0.001). This
      decrease was more pronounced in the more active patients. None of the T cell
      activation markers was shown to distinguish different degrees of disease
      activity. However, the percentage of NK cells was significantly reduced in active
      disease states (P < 0.01). Decreased numbers of NK cells could potentially reduce
      the resistance of SLE patients to infectious organisms.

PMID- 8268971
TI  - Detection of anti-phospholipid and anti-DNA antibodies and their idiotypes in
      newborns of mothers with anti-phospholipid syndrome and SLE.
AB  - The titers, isotypes and idiotypes of antiphospholipid and anti-dsDNA antibodies
      were determined in seven pairs of mothers with antiphospholipid syndrome (APLS)
      and their offspring, in 11 pairs of SLE mothers and their matched infants and in
      seven respective pairs of healthy subjects. In addition, maternal as well as
      fetal sera were evaluated for the presence of anti-SSA (Ro), anti-SSB (La) and
      anti-70 kd RNP autoantibodies. In the sera from APLS patients, as well as in the
      sera from their offspring, the mean antibody titer of IgG aCL was found to be
      significantly higher then the corresponding value in the control group (P <
      0.01). Highly significant increased titers of IgG anti-DNA antibodies were found
      in the sera of SLE mothers and their matched offspring (P < 0.0008). The
      prevalence of anti-SSA, anti-SSA, and anti-70Kd RNP antibodies was lower then
      that of antiphospholipid and anti-dsDNA antibodies. Only one of the respective
      offspring had increased levels of these antibodies. The quantity of maternal
      antibodies transferred to the fetus was depended on their concentration in the
      maternal circulation, as well as on their type and specificity. Follow-up of
      newborn sera showed a progressive decrease in the antiphospholipid antibody
      titers during 3 months. After 6 months it was undetected. Our results point to a
      transplacental transfer of aCL and anti-DNA antibodies, a phenomenon which is not
      necessarily associated with respective clinical manifestations, in contrast to
      the classical humoral mediated autoimmune diseases (e.g. myasthenia gravis).

PMID- 8268972
TI  - Standardized ultraviolet-A exposure provokes skin reaction in systemic lupus
      erythematosus.
AB  - The immediate, 1 day and 14 days skin reaction was determined in 23 female SLE
      patients and 23 age-matched controls after standardized exposure to ultraviolet
      light of the UV-A wavelengths (320-440 nm). Eighteen of the patients and 12 of
      the controls were photosensitive by history. Eight separate sites on the buttocks
      were exposed to UV-A light, four sites at doses between 42 and 252 kJ/m2 and four
      sites with longpass filters (320, 345, 360 and 375 nm). The reactions on test
      sites were graded by two independent observers unaware of given doses of filter
      location. All patients and controls reacted with immediate erythema
      irrespectively of the presence or absence of photosensitivity. After 1 day, 39%
      of controls and 78% of patients had erythema and the reactions were more
      pronounced to longwave UV-A light (> 320 nm) in the patients (P < 0.001). After
      14 days, six patients, but no control, had persistent erythema (P = 0.04).
      Interestingly, three of the four patients without anamnestic photosensitivity did
      not react on days 1 or 14, while the pattern seen in the controls on day 1 was
      totally unpredictable with regard to reported photosensitivity. These findings
      strongly suggest that a considerable proportion of SLE patients show pathological
      skin reactions to physiological doses of longwave UV-A and not only the far more
      studied shortwave UV-B (290-320 nm). The responsible chromatophore for the UV-A
      reaction is not known.

PMID- 8268973
TI  - Effect of sex on the induction of anti-DNA antibodies in normal mice immunized
      with bacterial DNA.
AB  - Immunization of normal mice with bacterial DNA elicits a significant IgG anti-DNA
      response and has been explored as a model of systemic lupus erythematosus. To
      determine whether this induced response is influenced by sex, we have measured
      anti-DNA levels in normal male and female BALB/c mice immunized with single
      stranded DNA from E. coli as complexes with methylated bovine serum albumin
      (mBSA) in adjuvant. By ELISA assays, anti-DNA levels of immunized females were
      approximately 16-fold higher than those of immunized males; levels of antibodies
      to the mBSA carrier were similar, however. The antibodies from females and males
      showed a similar degree of cross-reactivity when assayed using other natural and
      synthetic DNA antigens, including mammalian DNA. These findings suggest the
      potentiation of anti-DNA production in females by antigen-specific mechanisms and
      provide further evidence that immunization with bacterial DNA replicates features
      of autoantibody production in SLE.

PMID- 8268974
TI  - Relationship of IL-2, IL-2R (CD25+), soluble IL-2R and IL-4 with disease activity
      in SLE patients.
AB  - The plasma levels of interleukin-4 (IL-4), interleukin-2 (IL-2), soluble receptor
      of IL-2 (IL-2R) and T cell expression of IL-2 receptor chain (CD25+) were
      determined in an attempt to relate these parameters with disease activity in
      systemic lupus erythematosus (SLE). IL-4, IL-2 and sIL-2R plasma levels of SLE
      patients were significantly higher than those of the control group (P < 0.05)
      while CD25+ expression was similar in both groups. Only sIL-2R levels were
      significantly higher (P < 0.05) in active than in inactive patients.

PMID- 8268975
TI  - Interstitial inflammatory and chronic tubulointerstitial lesions in lupus
      nephritis: comparison with those in IgA nephropathy.
AB  - The significance of interstitial inflammatory and chronic tubulointerstitial
      lesions was studied in relation to the severity of glomerular lesions in 62
      patients with lupus nephritis and 88 with IgA nephropathy. Severe interstitial
      inflammatory and chronic tubulointerstitial lesions were found in patients with
      severe glomerular lesions in both lupus nephritis and IgA nephropathy. In such
      cases, the serum creatinine levels at biopsy were high and the renal prognosis
      was poor regardless of the underlying disease (lupus nephritis or IgA
      nephropathy). No IgA nephropathy patients with nil or mild glomerular lesions had
      moderate or severe interstitial inflammatory and/or chronic tubulointerstitial
      lesions. In contrast, predominantly severe interstitial inflammatory lesions were
      found in 36% of lupus nephritis patients with nil or mild glomerular lesions. The
      prevalence of interstitial immune complexes deposition was markedly high in those
      with predominant interstitial inflammatory lesions. However, the severity of
      chronic tubulointerstitial lesions was mild and renal function did not
      deteriorate in the mean follow-up periods of 68.6 months. It is suggested that,
      besides the tubulointerstitial lesions attributable to the severe concomitant
      glomerular damage, the interstitial deposition of immune complexes per se plays a
      pathogenic role in the interstitial inflammatory lesions in lupus nephritis. Its
      prognostic significance, however, was considered to be minor.

PMID- 8268976
TI  - Pericardial complication of neuropsychiatric systemic lupus erythematosus.
AB  - A 28-year-old woman presenting with systemic lupus erythematosus stuck two sewing
      needles into her pericardium while psychotic from cerebral lupus. We believe this
      is a unique cause of acute pericarditis as a complication of SLE.

PMID- 8268977
TI  - Amaurosis fugax, Crohn's disease and the anticardiolipin antibody.
AB  - Crohn's disease is associated with a hypercoagulable state due to platelet or
      clotting abnormalities which may be responsible for the thromboembolic episodes
      seen in this condition. We report the occurrence of anticardiolipin antibodies in
      a patient with Crohn's disease who presented with Amaurosis fugax and suggest
      that these antibodies may be a further cause of the hypercoagulable state of
      Crohn's disease in some patients.

PMID- 8268978
TI  - Hepatic infarction in a pregnant patient with the 'primary' antiphospholipid
      syndrome.
AB  - We describe a patient with previous venous thrombosis while using oral
      contraceptives and recurrent pregnancy loss, who presented with massive hepatic
      infarction in the last trimester of the fourth gestation. Thrombocytopenia, the
      lupus anticoagulant (LA) and the anticardiolipin antibody (aCL) were detected and
      a diagnosis of a 'primary' antiphospholipid syndrome (APS) was made. The clinical
      and histological manifestations and the differential diagnosis, especially with
      DIC and pre-eclampsia, are discussed.

PMID- 8268979
TI  - Reflex seizures as initial manifestations of systemic lupus erythematosus in
      childhood.
AB  - We report a 10-year-old girl with reflex seizures characterized by visual and
      acoustic hallucinations, induced by visual and acoustic stimulations. The EEG
      showed atypical spike-wave discharges on the left temporo-occipital area,
      markedly activated by visual and acoustic stimuli (intermittent light, pattern
      reversal stimulation and monoaural right pure tone). The patient was treated with
      carbamazepine and seizure stopped within 7 months. After 10 months from the start
      of the therapy she developed signs of systemic lupus erythematosus.

PMID- 8268980
TI  - Cis effect of lacZ sequences in transgenic mice.
AB  - Transgenic mice carrying the 3-hydroxy-3-methylglutarylCoA reductase (HMG)
      promoter driving the Escherichia coli beta-galactosidase (lacZ) gene did not
      display the expected ubiquitous and constitutive expression in HMG-lacZ
      transgenic mice. The same promoter is however able to drive ubiquitous expression
      of the chloramphenicol acetyltransferase (cat) gene. Two lines of double HMG-lacZ
      and HMG-cat transgenic mice were obtained in which the two constructs were
      integrated at the same genomic sites. These mice expressed both reporter genes,
      but exclusively in the testes. These results suggest that the lacZ sequence might
      interfere negatively with the expression of the adjacent HMG-cat transgene.

PMID- 8268982
TI  - [The effect of stimulation of the cingulate cortex on the neuronal activity of
      the motor cortex in the white rat].

PMID- 8268981
TI  - Disruption of the G(i2) alpha locus in embryonic stem cells and mice: a modified
      hit and run strategy with detection by a PCR dependent on gap repair.
AB  - We have used an insertion vector-based approach to target the G(i2) alpha gene in
      AB-1 embryonic stem cells. 105 bp located 0.8-0.9 kb upstream of a disrupting Neo
      marker in exon 3 were deleted and replaced with an engineered Not I site, that
      served to linearize the vector. The 105 bp deletion served as a primer annealing
      site in a polymerase chain reaction (PCR) designed to detect the gap repair
      associated with homologous recombination. Both target conversion and vector
      insertion events were obtained ('hit' step). Clones that had inserted the entire
      targeting vector were taken into FIAU (1-[2-deoxy,2-fluoro-beta-D
      arabinofuranosyl]-5-ioduracil) counterselection to select against a thymidine
      kinase (TK) marker flanking the homologous genomic sequences and thus for cells
      that had excised the plasmid and the TK marker by intrachromosomal recombination
      ('run' step). Additional selection in G418 reduced the number of drug-resistant
      colonies at least five-fold. Thus, the Neo marker disrupting the homologous
      sequences allows for a more specific selection of the desired intrachromosomal
      recombination event in tissue culture. This modified 'hit and run' strategy
      represents a novel approach for vector design and the use of the polymerase chain
      reaction to detect targeting. It may be particularly useful for targeting genes
      that display a low frequency of homologous recombination. Germ line transmission
      of the mutated G(i2) alpha allele is also demonstrated.

PMID- 8268983
TI  - [Bile acid excretion by the major salivary glands].

PMID- 8268984
TI  - [The effect of aldosterone on the water-salt metabolism of the brown fatty
      tissue].

PMID- 8268985
TI  - [Automation of the microfluorimetry of the dynamic content of membrane-bound
      calcium in the cat cerebral cortex].

PMID- 8268986
TI  - [The microsurgical revascularization of the brain with an autograft of the
      greater omentum].

PMID- 8268987
TI  - [A method for recording epicardial interferograms in synchronization with the
      phases of the heart cycle].

PMID- 8268988
TI  - [The cholinergic synapses of the associative temporal area of the neocortex in
      the realization of cognitive functions].
AB  - Subsynaptic fractions from light and heavy synaptosomes of the cat temporal
      associative cortex were tested for choline-acetyltransferase activity in respect
      to ability of preverbal notion formation. Most of the fractions revealed no
      connection with the intellectual capacity. Involvement of the cholinergic
      synapses of the temporal associative cortex in functions of generalisation and
      abstraction, is discussed.

PMID- 8268990
TI  - [The role of hormones from the mucosa of the gastric antrum in regulating gastric
      secretion].
AB  - Removal of antral mucosa obviously reduced the sensitivity of glandulocytes to
      pentagastrin in dogs with Basov-Pavlov fistulae. Activation of the endocrinal
      cells of the antral mucosa after fundal and antral parts separation exerted an
      opposite effect. The data obtained suggest that, along with gastrin, there is
      another hormonal factor facilitating the action of gastrin in the antral mucosa.

PMID- 8268989
TI  - [The effect of immobilization on the morphofunctional properties of the lysosomal
      apparatus in neutrophilic leukocytes under beta-adrenoreceptor blockade].

PMID- 8268991
TI  - [A comparison of the effects of cyproheptadine and propranolol on the development
      of poststressor lesions of the gastric mucosa in inbred mice].
AB  - The effects of central cyproheptadine and propranolol were virtually the same but
      differed in their intensity. Differences between genotypes were shown to be able
      to determine the differences in effects of the blocking agents on different kinds
      of stress-induced stomach damage. The data obtained suggest that genotypic
      properties of the serotoninergic system can interfere considerably with the
      reactions of the stomach mucosa to emotional stress.

PMID- 8268992
TI  - [The action of regulatory peptides on the rate of fluid flow across the wall of
      the large intestine in the frog].

PMID- 8268993
TI  - [Digestion and metabolism in lactating cows depending on nutritional adequacy].

PMID- 8268994
TI  - [The role of transcallosal responses with an initial negativity in the formation
      of a pattern of interhemispheric asymmetry].
AB  - Negative-positive transcallosal homotopic responses (THR) occurred 2 times less
      frequently than the positive-negative ones in male cats, whereas the same ratio
      was 1:3 in female cats. The foci of maximal activity of the 1st and 2nd types THR
      did not coincide. The 2nd type THR were shown to have a lesser number of
      interzonal interconnections than in the case of the positive-negative potentials.
      A probable role of the negative-positive THR in limitation, contrasting of the
      increased excitability focus as well as the specifics of contraphasic THRs
      interaction in respect to the sex of animals, is discussed.

PMID- 8268995
TI  - [The circadian rhythm of the content of corticosteroids and of pain sensitivity
      in humans and rats].
AB  - The circadian relationships between blood corticosteroids and latent period of
      pain reaction to hot stimulation were investigated in man and rats. There were no
      correlation of blood corticosteroids levels and pain latent period but the latent
      period increased during those time of day when the corticosteroids levels were
      higher in total: man--morning and day, rats--evening and night.

PMID- 8268996
TI  - [The mechanisms of the development of hypoxia in rats under acute immersion
      hypothermia].

PMID- 8268997
TI  - [Elements of the theory of the extreme body state].
AB  - A concept of extreme state as a specific physiological category different from
      the general adaptation syndrome (stress-response), is presented. The extreme
      state occurs in case of a functional supertask when the price of urgent
      adaptation of the organism can involve life-threatening. The author presents a
      bio-economic approach to analysis of redistribution of the energy balance for
      maintenance of the organism's functioning in a critical situation, and suggests
      some ways of scientific-practical realisation of this approach.

PMID- 8268998
TI  - Will managed care succeed in rural areas? No.

PMID- 8268999
TI  - Will managed care succeed in rural areas? Yes.

PMID- 8269000
TI  - Measuring up. Congress reconsiders tax-exemption standards under reform.

PMID- 8269001
TI  - Reform jitters. Survey: 1993 a year of cutbacks.

PMID- 8269002
TI  - Home care CEO salaries.

PMID- 8269003
TI  - Precision maneuvers. A recent survey finds group practices are gearing up for
      reform and systems integration.
AB  - Physician group practices, like other providers, are experiencing the rapid
      transition to a new health care environment dominated by managed care
      penetration, at-risk capitation, and reform-related changes. Just how quickly
      things are changing is revealed by a new nationwide survey, which was conducted
      by Hospitals & Health Networks, the American Group Practice Association,
      Alexandria, VA, and Hamilton/KSA, Atlanta.

PMID- 8269004
TI  - Making the grade. Report cards will be used to measure the performance of health
      plans: how might they work?

PMID- 8269005
TI  - Hospitals and the health of their communities.

PMID- 8269006
TI  - Retooling leaders. "Facilitative leadership" helps clarify process and underpin
      culture change.

PMID- 8269007
TI  - The quality march. Part three of a national survey of quality improvement
      activities.
AB  - Taken as a whole, these findings from the National Survey of Hospital Quality
      Improvement Activities provide important baseline information on the current
      status of hospital quality improvement efforts. They also indicate those areas
      where hospitals perceive the greatest need for assistance and foretell the much
      needed expansion of CQI/TQM to clinical processes and activities involving a
      greater degree of physician participation.

PMID- 8269008
TI  - Westchester County, NY. Community hospitals join to attract employer contracts.

PMID- 8269010
TI  - Consumers rate their health plans.

PMID- 8269009
TI  - Christine Cassel on bioethics and the demands of health care reform. Interview by
      Karen Gardner.

PMID- 8269011
TI  - Providers organize to deal with managed care demands.

PMID- 8269012
TI  - Integrated information paves the way to better decision making on patient care.

PMID- 8269013
TI  - Competition is not a four-letter word.

PMID- 8269014
TI  - TQM and reform: making some connections.

PMID- 8269015
TI  - [Role of assisted fertilization techniques in the management of male sterility].

PMID- 8269016
TI  - [Treatment of functional uterine hemorrhages].

PMID- 8269017
TI  - [Echography in gynecology].

PMID- 8269018
TI  - [Risk of cancer of the ovary associated with infertility treatments. Critical
      analysis by the International Federation of Fertility Societies task force].

PMID- 8269019
TI  - [Present and future of melatonin in human and animal reproduction functions].
AB  - In the pineal gland, the photoperiodic information is translated into a chemical
      message, the nocturnal secretion of melatonin. The duration of this secretion is
      proportional to the length of the night and this is the way by which the
      photoperiodic information is integrated at the level of the central nervous
      system. It is now possible with melatonin to mime the effects of photoperiod on
      the reproductive axis. The daily melatonin secretion is directly generated in the
      circadian biological clock. Consequently, the periodic secretion of melatonin
      might be used as a circadian zeitgeber, able to entrain some circadian functions:
      it is thus possible to act with melatonin on circadian rhythms. At very large
      doses, melatonin seems to be able to act directly on gonads.

PMID- 8269020
TI  - [Can melatonin be used in out-of-season reproduction in domestic mammals?].
AB  - Melatonin, synthetized by the pineal gland, is the chemical messenger which
      allows seasonal animals to perceive day length changes. The nervous message,
      transformed into a hormonal one, triggers pulsatile activity of the LHRH neurons.
      Its sites and mode of actions are not completely elucidated. The most frequent
      mode of distribution is the sub-cutaneous implant, which induces an advance of
      the cyclical ovulatory activity of ewes and goats. The date of fertilization is
      advanced and fecundity of females is improved. It can be used alone, or in
      association with other hormonal treatments, or after an artificial photoperiodic
      treatment. Under these conditions, it allows a quantitative and qualitative
      increase in out-of-season sperm production in rams and he-goats.

PMID- 8269021
TI  - [Fertility after cytostatic treatments].
AB  - Antimitotic chemotherapy and radiation therapy can induce temporary or permanent
      infertility in men, transitory amenorrhea or premature ovarian failure in women,
      and genetic mutations responsible of fetal deaths or congenital malformations in
      the progeny. Alkylating agents and radiotherapy can provoke definitive male
      infertility and ovarian failure, but individual susceptibility seems quite
      variable. In man, return of spermatogenesis can still be observed more than 10
      years after treatment and pregnancies are obtained with very low sperm counts. In
      women, the progressive depletion of the follicular pool explains the increasing
      frequency of ovarian failure, with lower doses of treatment. Antimitotic and
      immunosuppressive therapy can also induce irreversible lesions in children's
      gonads.

PMID- 8269022
TI  - [Spermatogenesis protection: myth or reality?].
AB  - Cytotoxic agents used in various therapies (anticancer treatments in particular)
      are known to be very deleterious to male fertility. In these situations, both
      quantitative (oligo and azoospermia) and qualitative alterations of the male
      reproductive system occur. What are the various possibilities to protect male
      reproduction? Sperm cryo-storage, prior to the beginning of chemotherapy and/or
      radiotherapy, is one possibility. However this possibility can only be offered to
      a relatively limited number of patients, due to the fact that the disease itself
      often causes gonadal abnormalities. Another possibility is the substitution of
      the most cytotoxic drugs by less deleterious agents, as well as, the reduction of
      the doses used in the therapeutic regimens. Progress in this field however
      remains very slow. Therefore, the use of various protective agents appears to be
      necessary. Of all the agents so far tested (anti-oxidants, GnRH analogs, FSH,
      steroids), the combination of medroxyprogesterone acetate and testosterone
      (MPA+T) is the one which has been the most studied both in men (contraception)
      and in rodents (contraception and protection). From a series of experiments using
      MPA+T in male rats, it appears that both qualitative and quantitative protection
      of fertility can be achieved against chemo- and radiotherapy. Progress in this
      field should be the prelude of clinical trials. This transfer from animals to
      men, should result as one of the activities of a pluri-disciplinary group
      supported by INSERM and entitled "Prosperm". The dialogue established in this
      group between researchers and physicians offers new perspectives in the domain of
      protection of spermatogenesis, at a time when this is most needed.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269023
TI  - [Conservation of sperm before cancer therapy. An efficient measure for preserving
      chances of future conception].
AB  - In recent years, chemotherapy and radiations for cancer patients has become
      increasingly successful, and sustained remissions have been achieved. However, in
      young men, most of the current therapies still presently induce temporary or
      permanent sterility without any means of prediction. The present paper largely
      based on data accumulated over two decades at CECOS Paris-Bicetre reassess the
      clinical role of semen cryopreservation from young men with cancer before
      chemotherapy and/or radiotherapy. Recent use of assisted reproduction
      technologies with pretherapy cryopreserved specimens (including semen of poor
      quality) has provided a growing number of pregnancies. These new data strongly
      reaffirm that semen cryopreservation should be offered to all men diagnosed with
      cancer since it presently provides the only reasonable chance of establishing a
      pregnancy after therapy.

PMID- 8269024
TI  - [Value of adding antibiotics to frozen bovine semen: the example of mycoplasmas
      and campylobacters].
AB  - Two studies have been conducted to control opportunistic pathogen bacteria in
      frozen bovine semen. The first one was reported by Shin et al. (1988) and was
      based on (a) an experimental in vitro contamination of raw bull semen with
      various types of bacteria, (b) adding several antibiotics, alone or in
      combination with different concentrations. The second experiment, performed in
      our laboratory, was designed to compare from 240 split ejaculates the effect of
      adding concentrated solutions of antibiotics to the raw semen vs control (ie
      addition of antibiotics in the extender). The combination of gentamicin (500
      micrograms/ml)-tylosin (100 micrograms/ml)-linco-spectin (300/600 micrograms/ml)
      was found to be the most effective on the strains of bacteria tested. The
      addition of a concentrated solution of antibiotics to the raw semen was not found
      here to be of any advantage on the numbers of CFU. Furthermore, such a protocol
      contributed to significantly decrease the percentage of motile spermatozoa. In
      conclusion, opportunistic pathogens such as those here studied may be kept under
      control with the appropriate antibiotics and with no deleterious effect on semen
      parameters provided that they are added at the adequate concentrations in the
      diluents used for semen cryopreservation.

PMID- 8269025
TI  - [Binding specificity and stimulation efficacy of gonadotropins].
AB  - Gonadotropins are made up of two glycoproteic subunits bound by non-covalent
      linkages. One subunit, named alpha, is common in all glycoprotein hormones; the
      second subunit, named beta, is specific for each hormone. This review present our
      recent results on dependence of activity on quaternary structures, on affinity
      and specificity of the binding of gonadotropins to their receptors and
      stimulation efficiency of gonadotropins.

PMID- 8269026
TI  - [Use of GnRH to stimulate the reproductive function in domestic ruminants].
AB  - Therapeutic effects of GnRH or its analogs have been tested in various
      physiological and pathological situations in domestic ruminants. Without any
      previous selection based on clinical observations, these treatments have a low
      efficiency to improve reproductive parameters. When used to induce ovulation in
      anoestrous females, GnRH or its analogs are less efficient than progestagen
      treatments associated with PMSG. On the contrary, GnRH can be used in females
      bearing follicular cysts or for the treatment of repeat breeders. Association of
      GnRH or its analogs to superovulation treatments is a new field of investigation.
      Additional experiments are necessary to show if it is possible to improve the
      response of superovulated females with such treatments.

PMID- 8269027
TI  - [Recent data on the gonadoliberin receptor and the neuropeptide control
      mechanisms for gene expression of gonadotropin hormones].
AB  - GNRH plays a pivotal role in the neurohormonal control of reproduction by
      promoting hte secretion of pituitary gonadotrophins, LH and FSH. GnRH also
      stimulates the synthesis of constitutive gonadotrophin subunits alpha and beta
      and its own receptor number. Gonadotrophin synthesis appears to be regulated by
      GnRH through various molecular mechanisms that include, in a complementary and in
      some cases differential manner, enhanced transcriptional activity of subunit
      genes and polyadenylation of transcripts. The latter is known to result in
      increased stability and/or translational activity of mRNAs. These effects of GnRH
      are mimicked by the direct activation of protein kinases A and C, two different
      but possibly interconnected signalling pathways that may account for the
      pleiotropic and concerted alterations of both synthesis and release of
      gonadotrophins. GnRH operates on the gonadotropic cell level via a transmembrane,
      G-protein coupled receptor, the structure of which has recently been determined
      by molecular cloning. This receptor differs from the other members of hte super
      family essentially by a rather short length (only 327-328 amino acids) and a
      truncated carboxyterminus. Recent experiments suggest a genomic control of the
      GnRH receptor synthesis, especially by GnRH itself, the importance, and role of
      which remains to be established for the pituitary gonadotropic function.

PMID- 8269028
TI  - Possible models describing enterocyte replacement in mouse Peyer's patch follicle
      associated epithelial tissue.
AB  - Epithelial cells emerging from intestinal crypts surrounding Peyer's patch
      lymphoid follicles can be shown in chimaeric mice to adopt a wedge-like formation
      during migration to a central zone of cell extrusion (Schmidt et al. 1985).
      Similar tissue taken from normal mice has been used as a model in the present
      work to investigate how such a pattern of convergent migration might take place.
      Tissue treated cytochemically to reveal differences in surface alkaline
      phosphatase activity enabled a number of cell surface area measurements to be
      carried out by image analysis. The position where these measurements had been
      taken was then related to the geometrical centre of the tissue. Epithelial cell
      surface area halved during migration from edge to centre of these disc-like
      structures. An equation used to describe the positional dependence of this change
      had the form rho(r) = 6.86r(-0.24), where rho is cell density and r is cell
      distance from the centre measured in micrometers. Further calculation showed this
      decrease to be insufficient to explain all features associated with convergent
      migration. Differential changes occurring in the rate of cell migration and
      premature cell loss were also considered as possible factors affecting migration
      patterns. Mathematical modelling of these variables produced a migration pattern
      consistent with previous experimental findings. This model assumes that half the
      cell population is lost during migration and that cell migration rate near the
      centre is four times greater than at the edge. It should be possible to test this
      latter prediction in future experiments.

PMID- 8269029
TI  - Water and ion shifts in mouse intestinal cells following VIP stimulation.
AB  - The cytoplasmic water content and the concentrations of Cl-, Na+ and K+ were
      measured by X-ray microanalysis and cryoelectron microscopy in mouse jejunal
      crypt enterocytes, Paneth cells, villus enterocytes, smooth muscle cells and in
      the basal lamina lining the crypt epithelium. Values found in controls were
      compared with those measured after in vivo stimulation of intestinal electrolyte
      secretion by vasoactive intestinal polypeptide (VIP). Na+ extrusion via the
      Na+/K+ pump appears to be rate-limiting for electrolyte secretion through crypt
      enterocytes in this model. VIP depolarizes smooth muscle cells and affects the
      ion distribution in villus enterocytes.

PMID- 8269030
TI  - Extensive deposition of basement membrane by tumours: a prognostic factor? A
      reappraisal.
AB  - A loss of the continuous linear deposit of basement membrane around invasive
      carcinomas has been suggested to correlate with their increased invasiveness. In
      contrast, extensive basement membrane deposition would represent a more
      favourable prognosis. The Engelbreth-Holm-Swarm (EHS) tumour, a transplantable
      neoplasm, is widely used for its ability to synthesize and deposit large amounts
      of basement membrane components. We have evaluated the metastatic potential of
      this neoplasm 2 months after subcutaneous inoculation. Histological examination
      of lung sections revealed the presence of numerous metastatic foci. The
      metastatic cells retained their organization into clusters surrounded by
      extracellular matrix. Both the 72 kDa and the 92 kDa type IV collagenases were
      detected by zymography in Triton or urea extract (matrigel) of primary tumour.
      These results cast doubt on the hypothesis that the extensiveness of basement
      membrane deposition might always be of prognostic value by being inversely
      correlated with the degree of invasiveness of a carcinoma.

PMID- 8269031
TI  - Differences in secretory profiles of epithelial cell cultures derived from human
      tracheal and bronchial mucosa and submucosal glands.
AB  - The respiratory tract contains macromolecules produced by various epithelia
      including tracheal and bronchial mucosa and submucosal glands. The objectives of
      this study were to elucidate and compare the growth and secretory profiles of
      epithelial cell cultures derived from the human tracheal (TC) and bronchial
      mucosa (BC) and submucosal glands (GC). Most experiments were done on third to
      fourth passage cultures. Secretory glycoconjugates were characterized by a
      combination of gel filtration and anion-exchange chromatography after enzymic
      digestion with hyaluronidase of [3H]glucosamine and [35S]sulphate incorporated
      glycoconjugates secreted into the culture medium. Intracellular mucin-like
      glycoproteins were characterized by immunohistochemical staining with a human
      monoclonal respiratory mucin antibody. Results showed that the three cell types
      exhibited variable growth rates and secretory profiles. Doubling times of GC, BC
      and TC were 53, 75 and 80 h respectively. Immunocytochemical staining with the
      mucin antibody demonstrated positive reaction in GC and BC; TC showed no
      significant reaction. Mucin-like glycoproteins were detected in the spent media
      of GC and BC whereas TC, under the same conditions, did not produce any
      detectable amount of the glycoconjugates. Further, the mucin-like materials
      produced by GC and BC differed in their relative glycosylation and sulphation
      levels. The production of mucin was independent of substrate and vitamin A as the
      cultures were propagated on the plastic surfaces and the culture medium lacked
      vitamin A.

PMID- 8269032
TI  - Involvement of transforming growth factor-alpha and its receptor in the growth
      response of cultured human epidermal cells to retinoic acid.
AB  - Topical application of all-trans-retinoic acid (RA) to normal or photodamaged
      human skin causes pronounced growth effects on the epidermis (hyperplasia) by
      mechanisms poorly understood. This paper describes investigations concerning the
      possible involvement of transforming growth factor-alpha (TGF alpha) and its
      receptor in the growth stimulatory response of cultured human epidermal cells to
      RA. In a defined medium containing epidermal growth factor (EGF), RA (0.1-1.0
      microM) was found to increase epidermal cell number and size as determined by
      uptake of neutral red dye. The stimulatory effect of RA was inhibited by a
      blocking monoclonal antibody directed against the binding domain of the EGF
      receptor. Relative to conditioned medium from cells grown in the absence of RA,
      conditioned medium from epidermal cells treated with RA contained increased
      concentrations of functionally active TGF alpha as determined by
      radioimmunoassays and radioreceptor assays. In addition, we found a marked
      reduction in the ability of TGF alpha to bind epidermal cells treated with RA.
      Decreased TGF alpha binding capacity is thought to be due to the ability of RA to
      stimulate TGF alpha, thereby resulting in EGF receptor binding and
      internalization. These results lead us to speculate that RA is capable of
      stimulating the secretion of TGF alpha by epidermal cells in vivo. TGF alpha may
      then act in an autocrine manner to mediate the hyperplastic response of the
      epidermis to topical RA treatment.

PMID- 8269033
TI  - Hippocampus minor and man's place in nature: a case study in the social
      construction of neuroanatomy.
AB  - In mid-19th century Britain the possibility of evolution and particularly the
      evolution of man from apes was vigorously contested. Among the leading
      antievolutionists was the celebrated anatomist and paleontologist Richard Owen
      and among the leading defenders of evolution was Thomas Henry Huxley. The central
      dispute between them on human evolution was whether or not man's brain was
      fundamentally unique in having a hippocampus minor (known today as the calcar
      avis), a posterior horn in the lateral ventricle, and a posterior lobe. The
      author considers the background of this controversy, the origin and fate of the
      term hippocampus minor, why this structure became central to the question of
      human evolution, and how Huxley used it to support both Darwinism and the
      political ascendancy of Darwinians. The use of ventricular structures to
      distinguish humans from other animals appears to reflect an importance given to
      the ventricles that stretches back to ancient Greek medicine. This account
      illustrates both the extraordinary persistence of ideas in biology and the role
      of the political and social matrix in the study of the brain.

PMID- 8269034
TI  - Perforated axospinous synapses with multiple, completely partitioned transmission
      zones: probable structural intermediates in synaptic plasticity.
AB  - Analysis of axospinous synapses in the rat dentate gyrus, using three-dimensional
      reconstructions from electron micrographs of serial sections, revealed a novel
      synaptic subtype. Synapses of this subtype exhibit partitions that emanate from
      the postsynaptic spine head and invaginate the presynaptic axon terminal,
      dividing its portion contracted by the spine into distinct protrusions. Such
      complete spine partitions provide barriers between two to four discrete
      transmission zones, each one being formed by a separate axon terminal protrusion
      and delineated by a separate segment of the postsynaptic density (PSD). Spine
      partitions that differ from the complete ones were found in two other synaptic
      subtypes. One of these is characterized by a sectional partition the base of
      which is placed between the arms of a horseshoe-shaped PSD. Synapses of another
      subtype exhibit a focal partition the base of which is restricted to a
      perforation in a fenestrated PSD. Although both sectional and focal partitions
      invaginate a presynaptic axon terminal, they do not divide into separate
      protrusions and do not split a single transmission zone into disjointed entities.
      All three subtypes of partitioned synapses have nonpartitioned counterparts
      exhibiting segmented, horseshoe-shaped, or fenestrated PSDs. These observations
      suggest a model of structural modifications underlying synaptic plasticity.
      According to this model, synapses with multiple, completely partitioned
      transmission zones that appear to be designed as elements of an unusually high
      strength, represent pivotal structural intermediates in synaptic plasticity. The
      formation of such synapses from those that belong to other subtypes is postulated
      to result in a sustained increase in the efficacy of synaptic transmission.
      Conversely, a disassembly of complete partitions with the transformation of
      multiple transmission zones into a single one is proposed to lead to a persistent
      depression of synaptic responses.

PMID- 8269035
TI  - Structural synaptic correlate of long-term potentiation: formation of axospinous
      synapses with multiple, completely partitioned transmission zones.
AB  - Synapses were analyzed in the middle molecular layer (MML) and inner molecular
      layer (IML) of the rat dentate gyrus following the induction of long-term
      potentiation (LTP) by high-frequency stimulation of the medial perforant path
      carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1
      hour after the fourth high frequency stimulation. Stimulated but not potentiated
      and implanted but not stimulated animals served as controls. Using the
      stereological disector technique, unbiased estimates of the number of synapses
      per postsynaptic neuron were differentially obtained for various subtypes of
      axospinous junctions: For atypical (giant) nonperforated synapses with a
      continuous postsynaptic density (PSD), and for perforated ones distinguished by
      (1) a fenestrated PSD and focal spine partition, (2) a horseshoe-shaped PSD and
      sectional spine partition, (3) a segmented PSD and complete spine partition(s),
      and (4) a fenestrated, (5) horseshoe-shaped, or (6) segmented PSD without a spine
      partition. The major finding of this study is that the induction of LTP in the
      rat dentate gyrus is followed by a significant and marked increase in the number
      of only those perforated axospinous synapses that have multiple, completely
      partitioned transmission zones. No other synaptic subtype exhibits such a change
      as a result of LTP induction. Moreover, this structural alteration is limited to
      the terminal synaptic field of activated axons (MML) and does not involve an
      immediately adjacent one (IML) that was not directly activated by potentiating
      stimulation. The observed highly selective modification of synaptic connectivity
      involving only one particular synaptic subtype in the potentiated synaptic field
      may represent a structural substrate of the long-lasting enhancement of synaptic
      responses that characterizes LTP.

PMID- 8269036
TI  - Early areal differentiation of the human cerebral cortex: entorhinal area.
AB  - The early cytoarchitectonic specialization and area-specific differentiation of
      the prospective entorhinal cortex were studied in the postmortem human fetal
      brains (9.5-13.5 postovulatory weeks). At 10 weeks, using the Golgi method, we
      saw the appearance of area-specific large neurons (promoter neurons) with widely
      bifurcating apical dendrites situated at the outer margin of the cortical plate
      of the prospective entorhinal cortex. The analysis of the serial Nissl-stained
      sections revealed the concomitant appearance of a one-cell-thick layer
      (monolayer) at the interface between the cortical plate and the marginal zone and
      multilaminated spread of the deep part of the cortical plate. This is the
      earliest sign of area-specific cytoarchitectonic differentiation of all pallial
      regions characterized by the presence of the typical cortical plate. The first
      subareal differentiation within the entorhinal cortex begins at 13 postovulatory
      weeks with uneven development of fiber-rich lamina dissecans, which separates two
      cellular laminae principals (externa and interna), and with the appearance of
      characteristic cell islands of the prospective layer II. At rostral levels, cell
      islands begin to develop in the rostromedial entorhinal area at the subpial
      depths where large promoter neurons reside. At intermediate levels, both lamina
      dissecans and lamina principalis interna are well delineated. At caudal levels,
      lamina principalis interna is continuous with the upper subplate zone of the
      adjacent neocortex. Both area-specific neurons (promoters) and fiber-rich
      (afferent) strata develop synchronously during the earliest areal differentiation
      of the cerebral cortex. The precocious lamination of the cortical plate is the
      crucial event in the histogenesis of the entorhinal cortex.

PMID- 8269037
TI  - Parvalbumin-immunoreactive structures of the adult human entorhinal and
      transentorhinal region.
AB  - Parvalbumin-immunoreactive structures in the entorhinal and transentorhinal
      region of the adult human brain were studied using the avidin-biotin-peroxidase
      technique. Parvalbumin-immunoreactive neurons and fibers (axons) were present in
      all layers (layer nomenclature according to Rose, 1927). The density of fibers
      was high in the islands of the superficial cell layer pre-alpha and in layer pre
      beta and still heavier in pre-gamma. In the subjacent lamina dissecans it
      diminished abruptly and remained low in all layers of the internal principal
      stratum (layers pri-alpha, -beta, -gamma). This low density of fibers facilitated
      recognition of axon cartridges in layers pri-alpha and pri-gamma. Axon cartridges
      were also present within layers pre-beta and pre-gamma but were obscured by the
      dense fiber network there. Parvalbumin immunoreactivity was observed in the nerve
      cell soma and throughout the dendritic tree allowing the distinction of numerous
      nerve cell types. All parvalbumin-immunoreactive neurons belonged to the class of
      nonpyramidal neurons. Their lipofuscin pigment patterns differed distinctly from
      that of the pyramidal and modified pyramidal neurons. Based on their location,
      soma size, and dendritic arborization, they were grouped as large, medium-sized,
      and small neurons either of the multipolar or bipolar (vertical or horizontal)
      type. One type could be identified as an axo-axonic neuron, more specifically as
      a chandelier neuron generating axon cartridges. The dense fiber net within layer
      pre-gamma suggested the existence of another neuronal type, probably a neuron
      with an extended axonal ramification. The identified neurons were compared to
      neuronal types described in the literature from Golgi studies.

PMID- 8269038
TI  - Projection of the entorhinal layer II neurons in the rat as revealed by
      intracellular pressure-injection of neurobiotin.
AB  - A component of the perforant path, projection of the entorhinal layer II neurons,
      was investigated by recovering intracellularly labeled layer II neurons from the
      medial or intermediate entorhinal cortex in rats. The labeled layer II spiny
      stellate neurons had axon collaterals in layers I, II, and III of the entorhinal
      cortex as well as some axon collaterals in the subiculum. The stem axons gave
      rise to terminal axon branches that covered the entire extent (suprapyramidal
      blade, crest, and infrapyramidal blade) of the dentate gyrus and the CA2-3 fields
      in the transverse plane, forming a sheet-like formation. The axon arbor in the
      hippocampal formation spread up to 2 mm wide in a septotemporal direction. The
      sheet-like formation of the axon arbors was a narrow layer in the suprapyramidal
      blade and in the stratum lacunosum-moleculare of the CA2-3 fields. The layer
      became wider in the crest and infrapyramidal blade of the dentate gyrus. This
      study shows that the entorhinohippocampal circuit is not a simple circle from
      single cells level.

PMID- 8269039
TI  - Transneuronal changes in dendrites of GABAergic parvalbumin-containing neurons of
      the rat fascia dentata following entorhinal lesion.
AB  - The perforant path fibers from the entorhinal cortex form synapses with both
      granule cells and GABAergic, parvalbumin-containing (PARV) nongranule cells. The
      authors recently reported a persistent reduction of PARV-positive dendrites in
      the termination zones of entorhinal fibers in the hippocampus proper and fascia
      dentata after lesion of the entorhinal cortex. In the present study the authors
      analyzed the effects of de-entorhination on the ultrastructure of postsynaptic
      PARV-positive dendrites in the molecular layer of the fascia dentata. PARV
      immunocytochemistry was performed 2, 8, 55, and 360 days after an ipsilateral
      entorhinal lesion and, for comparison, 10 days after an ipsilateral fimbria
      fornix transection that disconnects the hippocampus from its septal and
      commissural afferents. Two days after entorhinal lesion, the authors observed
      swelling of the tissue close to the hippocampal fissure. Adjacent distal
      dendritic tips of PARV-positive dentate neurons appeared bloated and reduced in
      number. Reduction of PARV-positive dendrites in the former perforant path
      termination zone persisted 55 days after entorhinal lesion and could still
      observed after postlesional survival times for 1 year. Degenerating axon
      terminals were still present 55 days following lesion and PARV-positive dendrites
      exhibited abnormal invaginations. Fimbria transection did not result in similar
      dendritic changes in PARV-positive neurons. The results indicate a long-lasting
      process of reorganization in the molecular layer of the fascia dentata following
      entorhinal lesion and persisting changes in the morphology of PARV-immunoreactive
      dendrites. Entorhinal fibers seem to play a specific role for the maintenance of
      these dendrites, since similar changes did not occur following removal of septal
      and commissural fibers.

PMID- 8269040
TI  - Hippocampal mediation of stimulus representation: a computational theory.
AB  - The authors propose a computational theory of the hippocampal region's function
      in mediating stimulus representations. The theory assumes that the hippocampal
      region develops new stimulus representations that enhance the discriminability of
      differentially predictive cues while compressing the representation of redundant
      cues. Other brain regions, including cerebral and cerebellar cortices, are
      presumed to use these hippocampal representations to recode their own stimulus
      representations. In the absence of an intact hippocampal region, the theory
      implies that other brain regions will attempt to learn associations using
      previously established fixed representations. Instantiated as a connectionist
      network model, the theory provides a simple and unified interpretation of the
      functional role of the hippocampal region in a wide range of conditioning
      paradigms, including stimulus discrimination, reversal learning, stimulus
      generalization, latent inhibition, sensory preconditioning, and contextual
      sensitivity. The theory makes novel predictions regarding the effects of
      hippocampal lesions on easy-hard transfer and compound preexposure. Several prior
      qualitative characterizations of hippocampal function--including stimulus
      selection, chunking, cue configuration, and contextual coding--are identified as
      task-specific special cases derivable from this more general theory. The theory
      suggests that a profitable direction for future empirical and theoretical
      research will be the study of learning tasks in which both intact and lesioned
      animals exhibit similar initial learning behaviors but differ on subsequent
      transfer and generalization tasks.

PMID- 8269041
TI  - Mapping the differential effects of procaine on frequency and amplitude of
      reticularly elicited hippocampal rhythmical slow activity.
AB  - Hippocampal rhythmical slow activity (RSA, theta) was elicited in urethanized
      rats by high-frequency stimulation in the reticular formation. The effects of
      procaine infusion (0.5 microliters, 20% wt/vol) at various loci in the ascending
      system from pontine reticular formation to the medial septum/diagonal band area
      were investigated. It was found that procaine injected at points in the ascending
      system anterior to the supramammillary nucleus, in the region of the medial
      forebrain bundle or in the medial septum, reduced the amplitude of reticularly
      elicited RSA but had no effect on its frequency. Procaine injected at points in
      the ascending system from just anterior to the reticular formation stimulation
      site, up to, and including the supramammillary nucleus, reduced both the
      frequency and amplitude of reticularly elicited RSA. These results indicate that
      the frequency of reticularly elicited RSA is encoded in the supramammillary area,
      rather than in the medial septum/diagonal band as have previously been suggested.

PMID- 8269043
TI  - Banning tobacco advertising: can health economists contribute to the debate?

PMID- 8269042
TI  - Rapid decline of GABAA receptor subunit mRNA expression in hippocampus following
      transient cerebral ischemia in the gerbil.
AB  - Inhibitory neurotransmission may play an important role in neuronal degeneration
      following transient cerebral ischemia. We studied the effect of transient
      forebrain ischemia on the GABAA receptor system in the gerbil hippocampus.
      Gerbils were subjected to 5 minutes of bilateral carotid occlusion and were
      sacrificed at various times over 4 days following reperfusion. There was a
      substantial loss of pyramidal cells in the CA1 area of the hippocampus 4 days
      following ischemia. No cell loss was detected in CA3 pyramidal cells of the
      hippocampus, granule cell layer of the dentate gyrus, and ventroposterior medial
      and ventroposterior lateral nuclei of the thalamus at any time following
      ischemia. Examination of brain slices by in situ hybridization histochemistry
      revealed that a change in expression of the GABAA receptor alpha 1 and beta 2
      subunit mRNAs occurred in two phases following onset of reperfusion. The early
      phase (rapid) occurred within the first 4 hours following reperfusion. The
      expression of mRNAs significantly decreased (up to 25%) within 1 hour after
      occlusion in CA1 and CA3 pyramidal cell layers of the hippocampus and in the
      granule cell layer of the dentate gyrus. The expression of the mRNAs in these
      regions continued to decrease for 4 hours (up to 43%). In the second phase, which
      began between 4 and 12 hours following reperfusion, mRNA expression started to
      return to control levels in CA3 hippocampus and in the dentate. However,
      expression of both mRNAs continued to decline slowly in the CA1 pyramidal cell
      layer (up to 85%) over the next 3 days, concomitantly with degeneration of the
      CA1 pyramidal cells. Expression of mRNAs in the ventroposterior medial or
      ventroposterior lateral nuclei of the thalamus was similar to control values. To
      determine if a change in GABAA receptor distribution paralleled changes in
      receptor subunit mRNA expression, we also measured the binding of [35S]t
      butylbicyclophosphorothionate to GABAA receptor chloride channels. The t
      butylbicyclophosphorothionate [35S] binding decreased between 1 and 4 days after
      reperfusion in the dendritic fields of CA1 pyramidal cells (strata oriens,
      radiatum, and lacunosum-moleculare) but not in the pyramidal cell body layer.
      These results indicate that expression of GABAA receptor subunit mRNAs decrease
      well before CA1 pyramidal cell degeneration and loss of GABAA receptors. At
      present, it is not clear if an early loss of mRNA expression after an ischemic
      insult leads to a functional defect in GABAA receptors. If so, a loss of GABA
      neurotransmission may contribute to the development of neuronal degeneration
      following cerebral ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8269044
TI  - Equity and efficiency in Italian health care.
AB  - Health care finance and provision in Italy is unusual by international standards:
      public financing relies heavily on both general taxation and social insurance,
      and although the vast majority of expenditure is publicly financed, the majority
      of care is provided by the private sector. The system suffers, however, from a
      chronic failure to control expenditures and its record on perinatal and infant
      mortality is poor. Hospitals in Italy have a low bed-occupancy rate by
      international standards and the per diem system of reimbursing private hospitals
      encourages unduly long stays. Costs per inpatient day are high by international
      standards, but costs per admission are close to the OECD average. Ambulatory care
      costs are extremely low, but this appears to be due to the fact that GPs see so
      many patients that their role is inevitably mainly administrative. Consumption of
      medicines is extremely high, but because the cost per item is low, expenditure
      per capita is not unduly high. Despite the emphasis on social insurance, the
      financing system appears to be progressive. There is evidence of inequalities in
      health in Italy, and some evidence that health care is not provided equally to
      those in the same degree of need.

PMID- 8269045
TI  - The cost and efficiency of public and private health care facilities in Ogun
      State, Nigeria.
AB  - During the 1980s, Nigeria faced difficult economic conditions resulting in a
      severely constrained budget for public health services. To assess more carefully
      the costs and efficiency of the public and private health sectors, the Federal
      Ministry of Health in Nigeria undertook a comprehensive survey of health care
      facilities in Ogun State in 1987, the analysis of which is presented in this
      study. The findings suggest that there is potential to increase service delivery
      within existing budgets by more cost-effective allocation of inputs. Many public
      and private providers are not operating a full technical capacity. It also
      appears that public facilities are not using cost-minimizing combinations of high
      and low-level health workers, in particular, too many low-level staff are being
      used to support high-level workers. The cost analysis indicates that there are
      short-run increasing returns to scale for inpatient and nearly constant returns
      to scale for outpatient services. Economies of scope for joint production of
      inpatient and outpatient services are not being realized. A major implication of
      such analysis is that improved resource allocation decisions heavily depend on
      the existence of information systems at the health facility level which carefully
      integrate financial information with other appropriate and adequate measures of
      service inputs, health care quality, facility utilization and ultimately health
      status.

PMID- 8269046
TI  - Sometimes sensitive, seldom specific: a review of the economics of screening.
AB  - As the policy relevance of screening has increased, the application of the
      techniques of economic evaluation to screening has become widespread. This paper
      critically reviews the literature, and in so doing, highlights several ways in
      which future evaluations might be improved. These include: the adoption of a
      broader perspective regarding the questions to be addressed and the relevant
      margins; a reconsideration of the nature of the benefits and how they might be
      valued; and a greater emphasis being placed upon the role of individual behaviour
      and its potential impact on the outcome of economic evaluations.

PMID- 8269047
TI  - Recruitment methods for screening programmes: the price of high compliance.
AB  - High population compliance is seen as a prerequisite for an equitable screening
      service. To achieve high compliance fixed appointments are usually advocated.
      However, the costs of achieving high compliance have not previously been
      described. To assess the costs of achieving high compliance we have used a
      randomised trial of two common appointment methods: 800 women aged 45-49 living
      within 20 miles of Aberdeen were selected at random from the Community Health
      Index. They were randomly assigned to receive one of two letters--one offering a
      fixed appointment, the other inviting them to telephone to make an appointment.
      For a defined population fixed appointments achieved high compliance but only by
      reducing the opportunities for screening; for every 100 women screened, 110
      additional women were denied the opportunity of a screening test. In contrast the
      open letters of invitation achieved efficiency by increasing the number of women
      screened with given resources within a larger population. Thus for screening
      services with fixed budgets, high compliance is achieved only by screening fewer
      people.

PMID- 8269048
TI  - QALY league tables: handle with care.
AB  - This paper examines some of the difficulties in using QALY league tables in
      priority setting. Such tables sometimes are seen as being 'the' way to prioritise
      in health care and in particular, at present, with respect to priority setting
      among purchasers in the UK NHS. However the paper highlights the fact that the
      base on which such tables is built is small--relatively few studies in the
      English language using CUA have been conducted anywhere. Further, four issues
      which require handling with care are set out: (i) the relevant measure of cost in
      QALY league tables has to be restricted to health service resource use; (ii) the
      relevant measure of benefit in QALY league tables is clearly restricted to QALYs,
      thereby the utility of health gains and indeed the maximisation of the utility of
      health gains; (iii) in incorporating the results of CUA studies into QALY league
      tables there is a need for greater clarification on what the margin constitutes;
      and (iv) those who might use CUA results in QALY league tables need to ascertain
      whether the original context of the study will allow the results to be
      transferred to the local context of the decision maker. The paper suggests that
      there is a need to be quite clear what goal QALY league tables serve. The authors
      argue that the only legitimate (and clearly important) goal of QALY league tables
      is the maximization of the utility of health gains within a health service
      budget.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269049
TI  - Trends in the structure, productivity, effectiveness and unit costs of the
      Hospital and Community Health Services workforce in England: 1979-1991.
AB  - In this paper it is shown that there have been significant structural changes in
      the composition of the Hospital and Community Health Services (HCHS) workforce
      over the 1980s. The number of doctors, nurses and other medical professionals has
      grown at the expense of support staff such as ancillaries and maintenance
      workers. The number of agency and contract staff has risen rapidly, partly
      offsetting the loss of directly-employed support staff. Changes in the workforce
      have been compared with changes in activity, as measured by the cost-weighted
      activity index. According to this measure labour productivity has grown by a
      compound rate of 1.9% annually. Adjusting the labour force index for the wage
      bill of each group reveals productivity growth of 1.5%. The effectiveness of
      treatment, as proxied by the decline in avoidable perinatal mortality, has grown
      by 3.4% annually. Unit labour costs have fallen over the period at an average
      annual rate of 0.3%. The trend conceals wide fluctuations, with labour costs
      falling slowly during the first half of the decade, and rising strongly during
      the second half. Medical professionals benefited disproportionately from wage
      increases in comparison with other HCHS groups during the mid to late 1980s.

PMID- 8269050
TI  - Comment on the Jackson Hole initiatives for a twenty-first century American
      health care system.

PMID- 8269051
TI  - Chromatographic stability of glucose-silica.
AB  - Glucose-silica was prepared and packed into five 100 x 4.6 mm I.D. columns. These
      columns were tested initially with selected protein mixtures. Each of the columns
      was stored in one combination of buffer (100 mM sodium sulfate, 20 mM sodium
      phosphate, pH 6.8), temperature (4 or 20 degrees C), methanol and sodium azide.
      After a year, we found that storing glucose-silica columns in the buffer
      containing sodium azide or methanol at 4 degrees C was necessary to prolong
      stability in storage. However, glucose-silica also exhibited some dynamic
      instability.

PMID- 8269052
TI  - Analysis of N-acyl aminonaphthalene sulphonic acid derivatives with potential
      anti-human immunodeficiency virus activity by thin-layer chromatography and flame
      ionization detection.
AB  - A method for checking the purity of N-acyl aminonaphthalene disulphonic acid
      derivatives was required for a systematic study of the anti-human
      immunodeficiency virus activity of these agents. We describe the use of thin
      layer chromatography and flame ionization detection for the separation of these
      compounds, which are difficult to analyse by conventional methods. All the
      samples were prepared in methanol solutions (1 microliter) containing 5
      micrograms of aminonaphthalene derivative. These samples were applied to each
      type SIII Chromarod by a single injection and developed with pure methanol or a
      methanol-chloroform-ammonium hydroxide (35:55:10, v/v/v) solvent system.

PMID- 8269053
TI  - Determination of glycyrrhizin and glycyrrhetinic acid in traditional Chinese
      medicinal preparations by capillary electrophoresis.
AB  - A simple, rapid, accurate and reproducible capillary electrophoretic method was
      developed for the assay of glycyrrhizin and glycyrrhetinic acid in traditional
      Chinese medicinal preparations. The buffer solution used in this method was
      acetonitrile and 0.02 M sodium dihydrogen-phosphate solution adjusted to pH 7.5
      with 0.05 M sodium hydroxide. The linear calibration range was 0.04-2.00 mg/ml (r
      = 0.9988) for glycyrrhizin and 0.007-0.35 mg/ml (r = 0.9985) for glycyrrhetinic
      acid and recoveries were 98.1-101.3% for glycyrrhizin and 98.5-101.4% for
      glycyrrhetinic acid. The relative standard deviations were 1.02% (n = 6) for
      glycyrrhizin and 0.91% (n = 6) for glycyrrhetinic acid. The content of these two
      acids in Glycyrrhizae Radix and Glycyrrhizae Radix-containing Chinese medicinal
      preparations was successfully determined within 10 min.

PMID- 8269054
TI  - Laser-induced fluorescence detection of 9-fluorenylmethyl chloroformate
      derivatized amino acids in capillary electrophoresis.
AB  - Laser-induced fluorescence (LIF) was applied to the detection of 9
      fluorenylmethyl chloroformate (FMOC-Cl) derivatized amino acids separated by
      capillary electrophoresis. Fluorescence excitation was provided by a pulsed, KrF
      laser operating at 248 nm. A limit of detection of 5 x 10(-10) M was obtained for
      FMOC-alanine (S/N = 2). Separation of FMOC-derivatized proline, hydroxyproline,
      and sarcosine was achieved with a 20 mM borate buffer (pH 9.2), and the
      separation of FMOC-derivatized amino acid standard mixture was obtained using a
      20 mM borate buffer (pH 9.2) containing 25 mM sodium dodecyl sulfate.

PMID- 8269055
TI  - Anion-exchange chromatographic behavior of recombinant rat cytochrome b5.
      Thermodynamic driving forces and temperature dependence of the stoichiometric
      displacement parameter Z.
AB  - The HPLC anion-exchange isocratic retention behavior of the recombinant soluble
      core of wild type rat cytochrome b5 on Mono Q HR 5/5 was investigated as a
      function of temperature and sodium chloride concentration at fixed eluent flow
      rates. Retention was measured over a range of eluent flow-rates at a specified
      temperature to determine if true adsorption equilibrium could be approximated by
      the HPLC method. Apparent Van 't Hoff enthalpies of adsorption obtained from the
      HPLC retention data were positive, indicating an entropically driven spontaneous
      adsorption process, and were found to decline with increasing ionic strength. The
      retention results were interpreted in terms of the stoichiometric displacement
      model to obtain the apparent number of binding sites in the contact region, Z, as
      a function of temperature and of protein concentration. Z was found to depend
      significantly on temperature, even under conditions of nearly complete protein
      recovery, but did not depend on protein concentration at the low loadings
      studied.

PMID- 8269056
TI  - High-performance liquid chromatography of N-terminal tryptophan-containing
      peptides with precolumn fluorescence derivatization with glyoxal.
AB  - A precolumn fluorescence derivatization method combined with high-performance
      liquid chromatography is described for the sensitive and selective determination
      of N-terminal tryptophan-containing peptides. The peptides and tryptophan were
      converted into fluorescent derivatives with glyoxal in a moderately acidic medium
      (pH 4.5). The derivatives were separated on a reversed-phase column with
      isocratic elution with an aqueous mobile phase composed of acetonitrile, methanol
      and phosphate buffer (pH 6.0), and subsequently detected by fluorimetry. The
      derivatization technique provided the respective N-terminal tryptophan-containing
      oligopeptides with single fluorescent peaks in chromatography. The detection
      limits for the peptides were 55-382 fmol per 100-microliters injection volume at
      a signal-to-noise ratio of 3. The method also allowed the facile detection of an
      N-terminal tryptophyl fragment in the enzyme reaction mixture of dynorphin A with
      trypsin.

PMID- 8269057
TI  - Characterization of further association of the trimeric membrane protein porin by
      low-angle laser-light scattering photometry coupled with high-performance gel
      chromatography.
AB  - Porin (OmpF), a trimeric membrane protein, in an extract of the outer membrane of
      Escherichia coli gave a twin-peaked elution pattern on Sephacryl S-300HR gel
      chromatography in the presence of sodium dodecyl sulphate. The species eluting
      earlier and later were found to be the hexamer and trimer, respectively, from
      molecular mass determination by low-angle laser-light scattering photometry
      coupled with TSK-G3000SWXL gel chromatography. As the hexamer was dissociated
      into the trimer under the conditions of sodium dodecyl sulphate polyacrylamide
      gel electrophoresis, its presence had been overlooked. The addition of
      lipopolysaccharide, another component of the outer membrane, and subsequent
      dialysis induced association of the trimer, the product containing an appreciable
      amount of the hexamer.

PMID- 8269058
TI  - Evaluation of the capability of different chromatographic systems for the
      monitoring of thimerosal and its degradation products by high-performance liquid
      chromatography with amperometric detection.
AB  - Several liquid chromatographic systems using electrochemical detection on carbon
      electrodes were compared for the analysis of thimerosal and its degradation
      products, thiosalicylic acid and dithiodibenzoic acid. The studied separation
      systems included reversed-phase ion-suppressed chromatography, reversed-phase ion
      pair chromatography and ion chromatography. Amperometry and coulometry were
      evaluated as electrochemical detection techniques. The best method for thimerosal
      determination in ophthalmic solutions in terms of selectivity and sensitivity was
      ion-pair chromatography.

PMID- 8269059
TI  - Separation of pyridinecarboxylic acid isomers and related compounds by capillary
      zone electrophoresis. Effect of cetyltrimethylammonium bromide on electroosmotic
      flow and resolution.
AB  - The effect of the addition of cetyltrimethylammonium bromide (CTAB) to the buffer
      system in capillary electrophoresis on electroosmotic flow (EOF) is examined. At
      a CTAB concentration of 2.5 x 10(-4) M, EOF is anodal (flow towards the positive
      detector column end). With bare silica columns, anodal EOF first increases with
      increasing pH, up to a maximum in the pH range 4-6 depending on CTAB
      concentration, then decreases as pH is further increased. Optimum resolution of
      pyridinecarboxylic acid isomers is obtained at pH 2.7 with a 10 mM phosphate
      buffer and 30 mM CTAB. Using the same buffer system, optimum resolution for
      hydroxy-substituted pyridinecarboxylic acid isomers is obtained at pH 7.5. The
      use of CTAB results in a dramatic improvement in peak shape. Preliminary results,
      using an excimer laser operated at 248 nm, show that the fluorescence intensity
      of isonicotinic acid is substantially enhanced with the addition of 0.3% hydrogen
      peroxide to the phosphate buffer system.

PMID- 8269060
TI  - High-resolution separation of DNA restriction fragments by capillary
      electrophoresis in cellulose derivative solutions.
AB  - The performance and the efficiency of several cellulose derivatives as a
      molecular sieving agent for the capillary electrophoretic separation of DNA
      restriction fragments were investigated. All fragments up to 12,000 base pairs
      (bp) in the 1-kbp DNA ladder were resolved using linear polyacrylamide-coated
      capillaries filled with a buffer solution containing 0.5% cellulose derivative
      and the separation was completed within 17 min. High-concentration (0.7%)
      cellulose derivative solutions are effective for the complete separation of small
      fragments (50-1000 bp) of a HincII and a HaeIII digest of phi X174 DNA. A plate
      number of 0.5-1 x 10(6) plates per metre was achieved. The migration time and the
      resolution of DNA fragments were manipulated by varying several parameters, such
      as the size (viscosity) and the concentration of cellulose derivatives and the
      applied field strength. Some guidelines are presented for choosing these
      parameters, depending on the size of the DNA fragments being separated.

PMID- 8269061
TI  - 10th annual meeting of the American College of Epidemiology. November 7-8, 1991,
      Atlanta, Georgia. Disparities in health between minorities and nonminorities.

PMID- 8269062
TI  - Understanding the disparities in morbidity and mortality among racial and ethnic
      groups in the United States.

PMID- 8269063
TI  - The morbidity/mortality gap: what is the problem?

PMID- 8269064
TI  - Racial and ethnic differences in infant mortality and low birth weight. A
      psychosocial critique.
AB  - Recent studies on differences in infant mortality and low birth weight (LBW)
      among non-Hispanic whites, African Americans, and Mexican Americans were
      reviewed. Despite similar socioeconomic profiles, infant mortality among Mexican
      Americans (8/1000 live births) is less than half that of African Americans
      (18/1000 live births). In fact, the rate for Mexican Americans is identical to
      that of non-Hispanic whites. The data for LBW follow a similar pattern. What
      accounts for this unexpectedly low frequency of poor birth outcomes among Mexican
      Americans, especially given their economic disadvantages, reduced access to
      prenatal care, and exposure to discrimination based on ethnicity? Does adherence
      to a traditional Mexican cultural orientation protect otherwise high-risk Mexican
      Americans from poor pregnancy outcomes, as has been suggested? What is the
      "protective" social and psychological content of a traditional Mexican cultural
      orientation? And what are the implications of this line of reasoning for
      understanding the excess risk for poor birth outcomes among African Americans?
      This article explores these and related questions and concludes that new
      conceptual models are needed to guide research in this area.

PMID- 8269065
TI  - Health and the social status of blacks in the United States.
AB  - Inequalities in health status among various racial and ethnic groups form a
      prominent chapter in the history of public health in the United States.
      Inequalities are observed for a wide range of specific conditions, and evolve
      over time. Little evidence is available to support the contention that any
      sizable proportion of this overall inequality is caused by genetic factors
      operating at the population level. On the other hand, social status, as measured
      by proxy variables like income and education, does provide important information
      about the black-white differential in health status when used in standard
      epidemiologic analyses. What is often neglected in these analyses, however, is an
      attempt to define underlying pathogenic mechanisms that incorporate social
      processes. Causal explanations based on the broader observation that inequality
      determined by the structure of social relations is associated with health
      differentials in all populations offer a plausible theoretic framework. At the
      same time, the unique character of the experience of specific ethnic
      subpopulations must be accounted for. Any attempt to account for the impact of
      race with greater precision will require an attempt to define this demographic
      variable within the context of social class relations.

PMID- 8269066
TI  - Poverty, race, racism, and survival.

PMID- 8269067
TI  - Black-white differences in injury. Race or social class?
AB  - In the United States injuries are the leading cause of years of potential life
      lost and the leading cause of death for persons less than 45 years of age.
      Minority groups, particularly African-Americans, are disproportionately
      represented among those persons who die as a result of injury. Homicides account
      for much of this racial disparity; however, other forms of injury also contribute
      significantly to the differential. This paper examines death rates due to four
      types of injuries that contribute most to the black/white mortality gap. Our
      examination of death rates from 1984 to 1988 reveals no major reduction in the
      racial gap during the period, despite the initiation of some prevention efforts.
      We suggest that socioeconomic status rather than race is perhaps the major
      correlate of the social conditions and lifestyle choices which contribute to
      these injuries. We propose that injury prevention efforts must target both the
      causes and the consequences of socioeconomic inequality.

PMID- 8269068
TI  - Diet and nutrition as influences on the morbidity/mortality gap.
AB  - Dietary and nutritional factors underlie many conditions that contribute to
      health disparities between minorities and whites (e.g., infant mortality,
      cardiovascular diseases, diabetes, and certain cancers). Nutrition interventions
      may, therefore, be useful in reducing the "morbidity/mortality gap," that is, in
      helping to align the health profiles of minorities with those of the general
      population. The significance of diet and nutrition for the health status of
      minority populations may be greater than for whites because of a higher
      prevalence of risk factors or, in some cases, because the sensitivity to a given
      risk factor may be greater. The available data suggest possible racial and ethnic
      differences in diet-related attributable risks. However, the ability to clarify
      these findings is currently limited because relatively few nutritional
      epidemiologic studies have compared racial or ethnic groups. Although such
      studies are inherently complex, and the methodologic issues raised when studying
      minority groups add further challenges, further exploration of the role of diet
      and nutrition in relation to health disparities between minorities and whites may
      provide important new etiologic insights as well as indicate possible avenues of
      intervention.

PMID- 8269069
TI  - Smoking and the health gap in minorities.
AB  - Over the past decade, tobacco companies have targeted minority populations when
      advertising and promoting their products, containing the most widely available,
      legal addictive drug in the United States. This has contributed to a greater
      prevalence of cigarette smoking among some minorities and lower-income groups.
      Black males are more likely to smoke than white males and more often they smoke
      high-tar cigarettes. They are also less likely to quit smoking. Compared to the
      national average, a greater proportion of Hispanic males smoke, but not Hispanic
      females. Smoking prevalence rates among Asians and Native Americans are available
      from local surveys but there are no reliable national estimates. Blacks
      experience substantially higher rates of mortality and morbidity from all causes,
      heart disease, stroke, and smoking-related cancers as well as adverse pregnancy
      outcomes. Substantially lower rates of death from heart disease, stroke, and
      cancers are observed among Asians and Native Americans than among whites.
      Disparities in cigarette smoking among racial and ethnic groups do not mirror the
      observed racial and ethnic disparities in mortality. Other health risk factors,
      access to medical care and premature death from other causes, may partially
      explain the morbidity/mortality gap between minorities and nonminorities.
      Reliable national estimates on smoking prevalence and morbidity and mortality
      among minorities are needed. The role of tobacco use in the etiology of diseases
      that are disproportionately prevalent among minorities should be studied.
      Culturally sensitive and acceptable smoking interventions should be developed
      with the involvement of minorities.

PMID- 8269070
TI  - Race or racism? Addiction in the United States.
AB  - Data are presented contrasting racial and ethnic differences in the use of
      alcohol and other drugs, and in the morbidity and mortality consequent to
      substance abuse and dependence. In a review of recent studies, whites were found
      to have higher rates of use, abuse, and dependence than other racial and ethnic
      groups, despite the common perception that substance abuse is a "minority
      problem." Epidemiologists are challenged to use appropriate methodologies to
      study this discrepancy and delineate the roles of both race and racism in
      addiction.

PMID- 8269071
TI  - Drug abuse in the community. Race or racism?

PMID- 8269072
TI  - Environmental epidemiologic issues and minority health.
AB  - There exist great differences in morbidity and mortality across racial, cultural,
      and socioeconomic groups. Certain factors, like limited access to health care,
      are known to contribute to these differences. The contribution of other factors,
      like disparities in exposure to environmental hazards, is largely unknown as to
      the effect on minority groups' morbidity and mortality. This article describes
      select environmental hazards faced by minorities, such as lead toxicity in
      children, proximity to hazardous waste sites, and consumption of food
      contaminated with toxic substances, as well as the role of epidemiologists in
      documenting adverse health effects and participation in interventions to prevent
      them.

PMID- 8269073
TI  - Distribution of acquired immunodeficiency syndrome and other sexually transmitted
      diseases in racial and ethnic populations, United States. Influences of life
      style and socioeconomic status.

PMID- 8269074
TI  - Disease prevention programs for racial and ethnic minorities.
AB  - Many studies show a dramatic relationship between socioeconomic status and
      disease incidence. Clear racial and ethnic disparities also exist in the
      occurrence of diseases such as acquired immunodeficiency syndrome (AIDS),
      tuberculosis and syphilis. Consequently, to identify true risk factors for
      diseases when planning prevention programs, the effect of socioeconomic status
      must be differentiated from that of race or ethnicity. Further, different
      cultural heritages and social structures may affect how interventions are
      perceived or used and this must also be taken into account when planning
      programs. The Centers for Disease Control, through its National Center for
      Prevention Services, provides financial and technical assistance to state and
      local health departments to develop approaches that are culturally sensitive and
      linguistically appropriate to reach persons in racial and ethnic minority groups.

PMID- 8269075
TI  - Black communities' belief in "AIDS as genocide". A barrier to overcome for HIV
      prevention.
AB  - The belief that acquired immunodeficiency syndrome (AIDS) is a form of genocide
      targeted at the black population is prevalent in black communities in the United
      States. Public health authorities are distrusted, in part because of the legacy
      of the Tuskegee Study of untreated syphilis, a perceived racist experiment. For
      effective interventions to prevent the transmission of human immunodeficiency
      virus in black communities, genocidal fears and beliefs must be addressed and
      black community leaders should be involved in planning and implementation.

PMID- 8269076
TI  - Four diseases of disarray in public health.
AB  - The Institute of Medicine's report The Future of Public Health stated that
      "public health is in disarray" (Washington, DC: National Academy Press, 1988). I
      describe four "diseases" of this disarray: "hardening of the categories,"
      "hypocommitment to training," "tension headache between prevention and
      treatment," and "cultural incompetence." We must step outside the focus on
      problems and risk factors to use epidemiology to define health status positively
      and to identify health enhancing factors. This conference should catalyze
      innovative, holistic, culturally competent studies that will improve our well
      being.

PMID- 8269077
TI  - Data needed for improving the health of minorities.
AB  - Identified needs for minority health data, obstacles in obtaining the data, and
      potential solutions are reviewed. Vital statistics for whites and blacks have
      been available by states for many years. Recent revisions provide data on
      Hispanics, and new resolutions will provide data on Asian and Pacific Islander
      subgroups. But limitations persist in providing accurate statistics for minority
      subgroups. A major obstacle is the inadequacy of census denominator estimates,
      due to differential undercounts, paucity of postcensal estimates for states and
      localities, and the validity of the race and ethnicity data. Important issues
      revolve around quality, comparability, and intraperson variability of self
      identification in determining race and ethnicity, versus external assessment.
      National survey data have oversampled for black and Hispanic minorities, but not
      others. The Disadvantaged Minority Health Improvement Act of 1990 provides some
      solutions, including an extramural grants program to strengthen minority
      statistics, which the National Center for Health Statistics has implemented to
      improve minority health assessment at all levels.

PMID- 8269078
TI  - American College of Epidemiology 10th annual scientific meeting. Disparities in
      health between minorities and nonminorities. Recommendations for future research
      and action.
AB  - As a nation, we must accept and appreciate the fact of the racial and cultural
      diversity that characterizes America. Such diversity dictates that fundamental
      approaches and solutions to social problems, including health, need to be
      specific to local areas. From addressing health problems, the least controversial
      of social challenges, a degree of mutual respect can evolve that permits other
      issues to be addressed as well. Resolving health problems will require a
      coordinated effort of local, city, state and federal resources, both medical and
      non-medical. In addressing such problems, three important principles need to be
      embraced: 1) the development of a surveillance system to measure the problem and
      assess progress in terms of ultimate outcomes; 2) the continuing use of
      surveillance data to assess and modify strategy and to allocate resources as
      needed; and 3) the need in health programs in particular to assign far higher
      priority to "consumer satisfaction."

PMID- 8269079
TI  - Human T cell leukemia virus type I infection and chronic myelopathy.
AB  - The central nervous system (CNS) pathology of HTLV-I associated myelopathy or
      tropical spastic paraparesis (HAM/TSP) is reviewed, based mainly on 12 autopsy
      cases of Japanese HAM/TSP with a serological confirmation of HTLV-I infection.
      The essential histopathological feature of HAM/TSP is a chronic progressive
      inflammatory process heralded by parenchymal infiltration of memory CD4 cells.
      The inflammation involves both the grey and white matter of the spinal cord, and
      progresses for more than three years after the onset of neurological symptoms,
      resulting in preferential degeneration of the white matter. In cases with a
      history of more than nine years, however, the spinal cord lesions appears
      degenerative rather than inflammatory. Both the inflammation and the white matter
      degeneration are most conspicuous in the lower thoracic cord. The lateral
      funiculus is always and most severely affected. Although the parenchymal tissue
      degeneration is not confined to any particular long tracts, symmetrical
      degeneration of the lateral pyramidal tract is evident in all cases. The
      involvement of the posterior and anterior funiculi is variable and neurons are
      relatively well preserved. Since evidence for HTLV-I infection in the CNS is
      limited to detection of proviral DNA by the polymerase chain reaction (PCR) and
      isolation of the virus from CSF cells, autoimmune nature of the disease is
      suspected, but is supported by ample evidence for derangements of the host immune
      system compatible with those of autoimmune diseases. Recent studies on induction
      of white matter degeneration in the rat with a topographical similarity to human
      HAM/TSP is also briefly reviewed. However, in the rat disease, inflammatory cell
      infiltrations are inconspicuous.

PMID- 8269080
TI  - Microglial reaction in the rat cerebral cortex induced by cortical spreading
      depression.
AB  - The response of microglial cells to cortical spreading depression (CSD) was
      studied in rat brain by immunocytochemistry. CSD was elicited for one hour by the
      topical application of 4M potassium chloride solution and the microglial reaction
      examined immunocytochemically after 4, 16, 24 and 72 hours. CSD was sufficient to
      induce a microglial reaction throughout the cortex at 24 hours. Activated
      microglial cells furthermore showed a striking de-novo expression of major
      histocompatibility complex class II antigens. In contrast, no microglial reaction
      was observed in the cortex of sham-operated animals. This microglial reaction in
      response to CSD was not associated with histologically detectable neuronal
      damage. These results support the view that microglial cells are extremely
      sensitive to changes of the brain microenvironment. Their activation may be
      related to changes of ion homeostasis in the brain which are not sufficient to
      trigger neuronal injury.

PMID- 8269081
TI  - Subsets of glioblastoma multiforme defined by molecular genetic analysis.
AB  - Glioblastoma multiforme is a clinically and histologically heterogeneous lesion;
      however, to date, it has not been possible to subdivide glioblastomas on a
      clinical, histopathological or biological basis. Previous studies have
      demonstrated that loss of portions of chromosomes 10 and 17 and amplification of
      the epidermal growth factor receptor (EGFR) gene are the most frequent genetic
      alterations in glioblastoma. We therefore examined 74 glioblastomas from 67
      patients for loss of heterozygosity on chromosomes 10 and 17, and for
      amplification of the epidermal growth factor receptor gene, to determine whether
      glioblastomas can be subtyped on a genetic basis. Using Southern blot analysis we
      were able to detect different patterns of genomic alterations. Eighteen of 67
      informative patients were characterized by a loss of heterozygosity on the short
      arm of chromosome 17 in the tumor tissue. Forty-five of 64 informative patients
      showed a loss of heterozygosity on chromosome 10. Amplification of the epidermal
      growth factor receptor gene was noted in 25 of 67 patients and was restricted to
      those glioblastomas that had lost portions of chromosome 10. Epidermal growth
      factor receptor gene amplification occurred significantly more often in patients
      without chromosome 17p loss than in patients with chromosome 17p loss (p = 0.01).
      In addition, those glioblastomas with a loss of chromosome 17p occurred in
      patients significantly younger than those with glioblastomas characterized by
      EGFR gene amplification (p = 0.001). These data emphasize the genetic
      heterogeneity of glioblastoma and suggest the division of glioblastoma into
      genetic subsets.

PMID- 8269082
TI  - The molecular and cellular biology of tau.
AB  - Tau protein was a well-studied molecule before it was discovered in the Alzheimer
      neurofibrillary tangles. As a microtubule-associated protein (MAP), it continues
      to be of interest to microtubule biologists who have provided a rather rich
      knowledge about this protein. Recent work suggests that tau, a neuronal MAP, is
      capable of generating some features of an axonal shape and an axon-like
      organization of the cytoskeleton. The importance of tau in pathology stems from
      its relationship to Alzheimer paired helical filaments and dystrophic neurites.
      Tau was first believed to be a component of paired helical filaments based upon
      immunocytochemical grounds (1-6) and then conclusively demonstrated by protein
      chemical techniques (7-9). Most recently it was shown that bacterially expressed
      tau fragments from the microtubule-binding domain can self-assemble into paired
      helical filaments that resemble those from the Alzheimer brain (10).

PMID- 8269083
TI  - Altered tau and neurofilament proteins in neuro-degenerative diseases: diagnostic
      implications for Alzheimer's disease and Lewy body dementias.
AB  - The neuronal cytoskeleton is one of the most profoundly altered organelles in
      late life neuro-degenerative disorders that are characterized by progressive
      impairments in cognitive abilities. The elucidation of the protein building
      blocks of these organelles as well as advances in understanding how these
      proteins become altered in Alzheimer's disease (AD) and other less common
      dementing illnesses, i.e., diffuse Lewy body disease (DLBD) or the Lewy body
      variant of AD (LBVAD), will provide insights into the molecular basis of these
      disorders. Within, we review evidence that normal adult human tau is abnormally
      phosphorylated and converted into the subunits of AD paired helical filaments
      (PHFs), and that Lewy bodies (LBs) represent accumulation of altered
      neurofilament (NF) triplet subunits. Although the precise biological consequences
      of PHF and LB formation in neurons is unknown, growing evidence suggests that the
      formation of PHFs and LBs from normal neuronal cytoskeletal proteins could have
      deleterious effects on neuronal function and survival. Finally, insights into the
      composition of PHFs and LBs could lead to the development of novel strategies for
      the timely and accurate diagnosis of AD, DLBD and the LBVAD.

PMID- 8269084
TI  - Ubiquitin in neurodegenerative diseases.
AB  - Immunochemical staining to detect ubiquitin has become an essential technique in
      evaluating neurodegenerative processes. Age related staining is seen in myelin,
      in nerve processes in lysosome-related dense bodies, and in corpora amylacea.
      There is a constant association between filamentous inclusions and the presence
      of ubiquitin. Intermediate filaments associated with ubiquitin, alpha B
      crystallin and enzymes of the ubiquitin pathway are the basis of Lewy bodies and
      Rosenthal fibres, as well as related bodies outside the nervous system.
      Neurofibrillary tangles in diverse diseases are associated with ubiquitin as are
      several other tau containing inclusions in both neurones and glia. Inclusions in
      motor neurones and non-motor cortex characterizing amyotrophic lateral sclerosis
      (ALS) and certain related forms of frontal lobe dementia can only be readily
      detected by anti-ubiquitin. Anti-ubiquitin also identifies both filamentous and
      lysosomal structures in neuronal processes as well as in some swollen neurones.
      Involvement of ubiquitin-containing elements of the lysosomal system appears
      important in pathogenesis of prion encephalopathies. Despite great advances in
      understanding cell biology of the ubiquitin pathway there are as yet few insights
      into the precise role played by ubiquitin in neuronal disease.

PMID- 8269085
TI  - The ubiquitin-mediated proteolytic pathway.
AB  - Ubiquitin modification of a variety of protein targets within the cell plays
      important roles in many cellular processes. Among these are regulation of gene
      expression, regulation of cell cycle and division, involvement in the cellular
      stress response, modification of cell surface receptors, DNA repair, and
      biogenesis of mitochondria and ribosomes. The best studied modification occurs in
      the ubiquitin-dependent proteolytic pathway. Degradation of a protein by the
      ubiquitin system involves two discrete steps. Initially, multiple ubiquitin
      molecules are covalently linked in an ATP-dependent mode to the protein
      substrate. The protein moiety of the conjugate is then degraded by a specific
      protease into free amino acids with the release of free and reutilizable
      ubiquitin. This process also requires energy. In addition, stable mono-ubiquitin
      adducts are also found intracellularly, for example, those involving nucleosomal
      histones. Despite the considerable progress that has been made in elucidating the
      mode of action and roles of the ubiquitin system, many problems remain unsolved.
      For example, very little is known about the cellular substrates of the system and
      the signals that target them for conjugation and degradation. The scope of this
      review is to summarize briefly what is currently known on the role of the
      ubiquitin system in protein turnover, and to discuss in detail the mechanisms
      involved in selection of substrates for conjugation and in degradation of
      ubiquitin-conjugated proteins.

PMID- 8269086
TI  - The role of synaptic proteins in the pathogenesis of disorders of the central
      nervous system.
AB  - Complex sets of nervous system functions are dependent on proper working of the
      synaptic apparatus, and these functions are regulated by diverse synaptic
      proteins that are distributed in various subcellular compartments of the synapse.
      The most extensively studied synaptic proteins are synaptophysin, the synapsins,
      growth associated protein 43 (GAP-43), SV-2, and p65. Moreover, synaptic
      terminals contain a great number of other proteins involved in calcium transport,
      neurotransmission, signaling, growth and plasticity. Probes against various
      synaptic proteins have recently been used to study synaptic alterations in human
      disease, as well as in experimental models of neurological disorders. Such probes
      are useful markers of synaptic function and synaptic population density in the
      nervous system. For the present, we will review the role of synaptic proteins in
      the following conditions: Alzheimer's disease (AD) and other disorders including
      ischemia, disorders where synapse-associated proteins are abnormally accumulated
      in the nerve terminals, synaptic proteins altered after denervation, and synaptic
      proteins as markers in neoplastic disorders. The study of the molecular
      alterations of the synapses and of plasticity might yield important clues as to
      the mechanisms of neurodegeneration in AD, and of the patterns of presynaptic and
      dendritic damage under diverse pathological conditions.

PMID- 8269087
TI  - Nervous system, muscles and systemic diseases--11th International Meeting on
      Neuromuscular Diseases, in Marseille, France, September 12-14, 1992.

PMID- 8269088
TI  - 4th International Symposium on Pharmacology of Cerebral Ischemia, in Marburg,
      Germany, from July 20-22, 1992.

PMID- 8269089
TI  - TTAA serves as the target site for TFP3 lepidopteran transposon insertions in
      both nuclear polyhedrosis virus and Trichoplusia ni genomes.
AB  - We have analysed TFP3 transposable elements from five independently isolated FP
      mutants of the Autographa californica nuclear polyhderosis virus (AcMNPV). We
      also analysed genomic copies of TFP3 elements amplified from the DNAs of the
      Trichoplusia ni cell line (TN-368) and T. ni larvae using the polymerase chain
      reaction (PCR). The sequences of all the newly isolated TFP3 elements closely
      resemble the previously described TFP3/1 element. Each of the transposons
      isolated from the virus mutants duplicated a TTAA tetranucleotide target site
      upon insertion into the viral genome. Four of these TFP3 elements transposed into
      three different 'TTAA' target sites within the 25 K gene (FP locus, map units 36
      37 of AcMNPV). The fifth TFP3 element inserted at a 'TTAA' site within the AcMNPV
      Hin dIII-E fragment. One genomic TFP3 element, amplified from the TN-368 cell
      line DNA by an inverse PCR method, duplicated a 'TTAA' tetranucleotide target
      site that is present only once in the homologous larval DNA sequence. These data
      suggest that mobilization of TFP3 into both viral and cellular sites is identical
      in specificity and mechanism.

PMID- 8269090
TI  - Genetic transformation and phylogeny of bacterial symbionts from tsetse.
AB  - Two isolates of bacterial endosymbionts, GP01 and GM02, were established in cell
      free medium from haemolymph of the tsetse, Glossina pallidipes and G. morsitans.
      These microorganisms appear similar to rickettsia-like organisms reported
      previously from various tsetse species. The 16S rRNA sequence analysis, however,
      placed them within the gamma subdivision of the Proteobacteria, phylogenetically
      distinct from most members of the Rickettsiaceae which align with the alpha
      subdivision. Distinct multiple endogenous plasmids are harboured by GP01 and
      GM02, suggesting that the two isolates are different. Restriction mapping
      analysis showed that one of the conserved plasmids is present in high copy number
      and is at least 80 kb in size. A heterologous plasmid pSUP204, which contains the
      broad host range oriV replication origin, was used to transfect bacterial
      cultures. The symbiont GM02 was transformed, and it expressed plasmid encoded
      resistance to the antibiotics ampicillin, tetracycline and chloramphenicol.
      Transformation of these symbionts may provide a novel means for expressing anti
      parasitic genes within tsetse populations.

PMID- 8269091
TI  - Genomic subtractive hybridization to isolate species-specific DNA sequences in
      insects.
AB  - Selective enrichment has been used in a number of instances for the isolation of
      species-specific sequences in prokaryotes. This paper reports the successful
      application of the technique to insects. Genomic probes were derived to the
      target species D. funebris and D. simulans. The method involves the biotinylation
      of non-target 'driver' DNA prepared from the closely related species D.
      melanogaster and its hybridization to homologous sequences in the target DNA.
      Hybrid molecules were removed from the reaction by incubation with streptavidin
      followed by phenol extraction, leaving a preparation enriched for target
      fragments. All DNA fragments isolated in the D. funebris experiments proved to be
      specific to that species. Five out of twenty-four fragments screened in the D.
      simulans experiments were specific when screened with homologous DNA and genomic
      DNA from its sibling species, D. melanogaster.

PMID- 8269092
TI  - Native and baculovirus-expressed forms of the immuno-protective protein BM86 from
      Boophilus microplus are anchored to the cell membrane by a glycosyl-phosphatidyl
      inositol linkage.
AB  - A glycoprotein (BM86) from the gut cells of the cattle tick Boophilus microplus,
      when used to vaccinate cattle, has been shown to protect cattle from tick
      infestation. A recombinant BM86 protein is the principal component of a novel
      tick vaccine currently under development. The nature of the anchorage of BM86 to
      tick gut epithelial cells has been investigated using BM86 from B. microplus and
      recombinant BM86 proteins expressed in insect cells using the baculovirus
      expression system. BM86 from B. microplus and a full length recombinant BM86 are
      shown to be anchored to the extracellular surface of tick gut epithelial cells
      and baculovirus-infected insect cells, respectively by a glycosyl-phosphatidyl
      inositol membrane anchor. A recombinant BM86 truncated by the removal of a
      hydrophobic region coding for thirty amino acids at the carboxy-terminal end was
      secreted from baculovirus-infected Sf9 cells. This secreted form of recombinant
      BM86 showed strong protective activity against ticks in cattle vaccinated with
      this protein.

PMID- 8269093
TI  - Gut-specific genes from the black fly Simulium vittatum encoding trypsin-like and
      carboxypeptidase-like proteins.
AB  - In haematophagous insects digestion of the blood meal provides nutrients for
      survival and essential components for egg production. We have isolated and
      partially characterized two gut-specific genes from the black fly Simulium
      vittatum. Sequence analysis revealed that both are highly similar to digestive
      proteases, one to trypsins and the other to carboxypeptidases. RNA blot analysis
      indicates that the expression of these two genes is regulated in a sex-specific
      manner; when fed the same sucrose-based diet, expression in males is
      substantially lower than in females. In females, expression of both genes is
      strongly induced by a blood meal. At 6 h after the blood meal the trypsin-like
      gene product was immunolocalized to the midgut epithelium and to the outer layers
      of the peritrophic matrix.

PMID- 8269094
TI  - Mediterranean fruit fly, Ceratitis capitata (Wiedemann), mitochondrial DNA: genes
      and secondary structures for six t-RNAs.
AB  - The polymerase chain reaction was used to amplify six mitochondrial t-RNAs for
      Ala, Arg, Asn, Ser, Glu and Phe between genes for mitochondrial NADH
      dehydrogenases 3 and 5. With respect to Drosophila yakuba the gene order and
      direction of transcription is completely conserved. Analysis of secondary
      structure shows complete conservation of the anticodon loops but a number of
      differences in the dihydrouridine and T psi C loops with respect to Drosophila.
      However, differences are such that tertiary interactions that stabilize stacking
      are preserved. The use of the reported sequence in combination with PCR to
      explore population variability is discussed.

PMID- 8269095
TI  - Codon usage patterns in chromosomal and retrotransposon genes of the mosquito
      Anopheles gambiae.
AB  - Codon usage was compiled for fourteen chromosomal genes and four retrotransposons
      from the mosquito Anopheles gambiae. Variation exists among chromosomal genes in
      the degree of bias. The genes showing the highest bias are probably most highly
      expressed. In these genes, the base composition at the third codon position is
      much richer in G + C than is the overall coding sequence. Thus, codon usage is
      biased toward G- or C-ending codons. Codon usage in each retrotransposon is quite
      different, not only from chromosomal genes but also from the other
      retrotransposons. Codon usage comparisons among homologous genes from An. gambiae
      and two other Dipterans, the yellow fever mosquito Aedes aegypti and the fruitfly
      Drosophila melanogaster, show that while there are similarities, particularly
      between An. gambiae and D. melanogaster in the preference for G- and C-ending
      codons, each species has evolved a distinct pattern of codon usage.

PMID- 8269096
TI  - Vitelline membrane biogenesis in Drosophila requires the activity of the alpha
      methyl dopa hypersensitive gene (I(2)amd) in both the germline and follicle
      cells.
AB  - The vitelline membrane of Drosophila eggs is composed of a family of proteins
      which are cross linked into an insoluble matrix with an overlying waxy layer that
      prevents desiccation. We present here three sets of experiments which show that
      integrity of the vitelline membrane requires the activity of the alpha methyl
      dopa hypersensitive (I(2)amdH or amd) gene in both egg chambers and follicle
      cells. We show that loss of amd activity either by dietary administration of
      inhibitors or in genetic mosaics of either the germ line or follicle cells leads
      to production of defective vitelline membranes and by in situ hybridization, that
      amd is expressed in both nurse cells and follicle cells. The amd gene product is
      the first non-structural protein gene described whose activity is required for
      vitelline membrane biosynthesis. Given its unique role in insects and its
      demonstrated sensitivity to dietary inhibitors, the amd gene product poses an
      attractive target for insect control.

PMID- 8269097
TI  - Codon preference of Aedes aegypti and Aedes albopictus.
AB  - The codon bias of two Aedes mosquito species was examined using a sign test. In
      general, there appeared to be some preference for C + G at the third base
      position, although this was not statistically significant. While amino acids such
      as phenylalanine and tyrosine clearly displayed biases, others such as valine and
      serine appeared to have little or no bias for any particular codon. Three
      homologous genes of Aedes aegypti and Drosophila melanogaster were compared using
      the chi-square test and the codon bias of the two species compared. Drosophila
      melanogaster was found to have a much stronger bias for C + G at the third base
      position compared to Aedes. The implications and usefulness of the codon bias are
      discussed.

PMID- 8269098
TI  - Plasmid modifications in a tick-borne pathogen, Borrelia burgdorferi, cocultured
      with tick cells.
AB  - We describe an in vitro system that will facilitate molecular analysis of the
      association between Lyme disease spirochetes and vector cells. We cocultured
      Borrelia burgdorferi continuously with two tick cell lines, RAE25 (from
      Rhipicephalus appendiculatus) and IDE8 (from Ixodes scapularis). A clone isolated
      after twenty-two passages with RAE25 cells had lost the largest (49 kb) plasmid,
      and probes containing information normally encoded on it, including genes for two
      surface proteins, hybridized to smaller plasmids. Spirochetes maintained with IDE
      8 cells showed a new 43 kb plasmid that hybridized to a probe made from the 49 kb
      plasmid. After reisolation from hamsters, these spirochetes carried a large
      plasmid (100 kb) that hybridized with the 49 kb plasmid. These changes may
      illustrate a plasticity that enables B. burgdorferi to adapt to different
      environments.

PMID- 8269099
TI  - Random amplified polymorphic DNA (RAPD) markers readily distinguish cryptic
      mosquito species (Diptera: Culicidae: Anopheles).
AB  - The usefulness of random amplified polymorphic DNA (RAPD) was examined as a
      potential tool to differentiate cryptic mosquito species. It proved to be a
      quick, effective means of finding genetic markers to separate two laboratory
      populations of morphologically indistinguishable African malaria vectors,
      Anopheles gambiae and An. arabiensis. In an initial screening of fifty-seven RAPD
      primers, 377 bands were produced, 295 of which differed between the two species.
      Based on criteria of interpretability, simplicity and reproducibility, thirteen
      primers were chosen for further screening using DNA from thirty individuals of
      each species. Seven primers produced diagnostic bands, five of which are
      described here. Some problematic characteristics of RAPD banding patterns are
      discussed and approaches to overcome these are suggested.

PMID- 8269100
TI  - Isolation of cDNAs encoding 6-phosphogluconate dehydrogenase and glucose-6
      phosphate dehydrogenase from the mediterranean fruit fly Ceratitis capitata:
      correlating genetic and physical maps of chromosome 5.
AB  - We have isolated and determined the nucleotide sequences for cDNA clones encoding
      glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase
      (6PGD) from the medfly Ceratitis capitata. The derived amino acid sequences for
      G6PD and 6PGD are presented and compared with G6PDs and 6PGDs from other species.
      The codon usage of the cDNA clones has little bias with the notable exceptions of
      arginine, glycine and leucine. The chromosomal location of the genes for 6PGD and
      G6PD were determined by in situ hybridization to salivary gland polytene
      chromosomes. This localization orients a genetic map of enzymatic loci and
      illustrates a remarkable similarity in the intra chromosomal order of homologous
      genes between Drosophila melanogaster and medfly.

PMID- 8269101
TI  - Thrombogenesis and anticoagulation in heart valve disease: towards a rational
      approach.

PMID- 8269102
TI  - Left atrial volume and function in valvular aortic stenosis.
AB  - To assess left atrial volume and function in aortic stenosis, 20 patients with
      this condition and 10 normal controls were studied. Atrial volumes were measured
      by echocardiography at mitral valve opening (maximal), onset of atrial systole (P
      wave of the electrocardiogram) and mitral valve closure (minimal), using biplane
      techniques. The maximal volume was greater in those patients with aortic stenosis
      as compared to the controls (74.8 +/- 26.4 cm3 vs. 46.4 +/- 11.9 cm3, p < 0.005),
      and was directly related to left ventricular mass (r = 0.77). The passive
      emptying volume (maximal minus onset of atrial systole) was similar in the two
      groups (21 +/- 8 cm3 vs. 18.7 +/- 5.9 cm3, p = NS), while active emptying volume
      (onset of atrial systole minus minimal) was higher in aortic stenosis (16.8 +/-
      5.2 cm3 vs. 10.2 +/- 2.5 cm3, p < 0.001). The total emptying volume (sum of
      passive and active) was slightly higher amongst those with aortic stenosis (37.4
      +/- 10.2 cm3 vs. 28.9 +/- 7.5 cm3, p < 0.05). The passive emptying fraction
      (passive emptying volume/maximal) was lower in the aortic stenosis group (0.28 +/
      0.08 vs. 0.40 +/- 0.05, p < 0.001), while the active emptying fraction (active
      emptying volume/volume at onset of atrial systole) was similar between the two
      groups (0.33 +/- 0.09 vs. 0.37 +/- 0.05, p = NS). Increased left atrial size in
      aortic stenosis is directly related to left ventricular mass and restores left
      atrial total emptying volume, despite the depressed passive emptying fraction.
      Left atrial dilatation thus represents an important compensatory mechanism,
      contributing to the maintenance of left ventricular stroke volume and cardiac
      output in severe aortic stenosis.

PMID- 8269103
TI  - Progression of aortic stenosis in adults: new insights provided by Doppler
      echocardiography.
AB  - Aortic stenosis is a progressive disease. The mechanisms and patterns of
      progression have been studied over the years using clinical assessment, cardiac
      catheterization, and more recently, Doppler echocardiography. Doppler is the
      ideal tool with which to study the progression of aortic stenosis since it
      provides accurate hemodynamic data non-invasively and, hence, can be repeated
      serially over long follow up periods. Recent Doppler echocardiographic studies
      have shown that the progression of aortic stenosis occurs with a wide range of
      individual variations, and that its rate and pattern cannot be predicted at the
      time of initial evaluation. However, it does follow a linear pattern, and
      individual trends can therefore be determined in a given patient. Symptoms lack
      specificity and, at a given point in time, do not predict progression. However,
      new and/or worsening symptoms are a mark of significant hemodynamic progression.
      The relationship between the cause of aortic stenosis and its progression remains
      imperfectly documented, and further longitudinal studies should focus on this
      question.

PMID- 8269104
TI  - In response to: Grunkemeier GL, Starr A. Alternatives to randomization in
      surgical studies.

PMID- 8269105
TI  - In response to: Grunkemeier GL, Starr A. Alternatives to randomization in
      surgical studies.

PMID- 8269106
TI  - In response to: Grunkemeier GL, Starr A. Alternatives to randomization in
      surgical studies.

PMID- 8269107
TI  - Hypercoagulability in the left atrium: Part I: Echocardiography.
AB  - Approximately 15% of patients with mitral valve disease will experience left
      atrial thrombosis and its consequences. The etiology and diagnosis of left atrial
      thrombosis are reviewed, stressing the importance of blood stagnation as the most
      important etiologic factor. Atrial fibrillation, a left atrial diameter greater
      than 60 mm and absence of significant mitral regurgitation are predictors of left
      atrial thrombosis in mitral stenosis. Left atrial thrombus can be detected in 50%
      of patients with all three factors; all influence blood stagnation. Smoke-like
      echoes in the left atrium, detected by echocardiography, provide a semi
      quantitative assessment of left atrial blood stagnation. The incidence of thrombi
      in patients with well marked smoke-like echoes is 60%, while in those without
      this echocardiographic finding it is only 9%. Smoke-like echoes provide an early
      warning system of conditions in the left atrium likely to lead to thrombosis
      unless the patient is anticoagulated.

PMID- 8269108
TI  - Hypercoagulability in the left atrium: Part II: Coagulation factors.
AB  - The relationship between a hypercoagulable state and intracardiac thrombus
      formation is reviewed, with reference to the pathophysiology of intracardiac
      thrombus in patients with acute cardioembolic stroke, and those with mitral
      stenosis. When the development or enlargement of intracardiac thrombus is
      followed serially by echocardiography, the diameter of the inferior vena cava is
      seen to decrease as the hematocrit increases, particularly in patients with
      negative water balance taking diuretics. These findings strongly suggest that
      dehydration could play an important role in the formation of thrombus. A
      hypercoagulable and secondarily enhanced fibrinolytic state exists in the cardiac
      chamber of patients with acute cardioembolic stroke or with intracardiac
      thrombus. This can be evaluated by plasma levels of fibrinopeptide A,
      fibrinopeptide B beta 15-42, thrombin-antithrombin III complex and D-dimer.
      Anticoagulant treatment suppresses thrombin activity in the cardiac chamber,
      allowing plasma fibrinolytic activity to predominate and reduce the size of the
      intracardiac thrombus.

PMID- 8269109
TI  - International standardization of laboratory control of oral anticoagulant
      therapy: a survey of thromboplastin reagents used for prothrombin time testing.
AB  - The prothrombin time (PT) test is the primary measurement in the laboratory
      control of oral anticoagulant treatment. The traditional expression of PT test
      results, either as percentage prothrombin activity or PT ratio, is inadequate for
      international communication and comparison because the values depend on the
      nature of the thromboplastin test system used. The WHO recommended universal
      scale of reporting PT results is based on calibration of local thromboplastin
      systems against an international reference preparation. This scale is the
      International Normalized Ratio (INR). Application of the INR scale in clinical
      practice should be encouraged by External Quality Assessment (EQA) schemes, which
      improve its precision. Many physicians are insufficiently aware of the different
      sensitivities of rabbit thromboplastins, which result in different
      anticoagulation intensities being employed in different clinics. Improvement in
      the situation can only be achieved by continuous education. The more widespread
      use of the INR scale should facilitate international comparison of
      anticoagulation results and eventually consensus on optimal target values. The
      introduction of the INR to countries not already using it, particularly the USA,
      should be strongly encouraged by all physicians with an interest in
      anticoagulation and especially those undertaking the long-term management of
      patients with prosthetic heart valves.

PMID- 8269110
TI  - The pharmacology of oral anticoagulants: implications for therapy.
AB  - All oral anticoagulants act by producing a functional deficiency of vitamin K,
      thereby impairing the normal synthesis of factors II, VII, IX and X. All, except
      dicumarol, are well absorbed after oral administration. They are highly protein
      bound and are mainly metabolized in the liver. A number of factors such as
      altered absorption, distribution, elimination, genetic factors, aging, vitamin K
      excess or deficiency, alterations in the level of vitamin K-dependent coagulation
      factors and drug interactions may affect response to oral anticoagulants. Adverse
      effects include hemorrhage, skin necrosis and teratogenicity. Phenindione can
      also cause serious hypersensitivity reactions. Five oral anticoagulants are
      available in Europe, although warfarin, phenprocoumon and nicoumalone
      (acenocumarol) are the most commonly used agents. The choice of oral
      anticoagulant is often influenced by previous experience and familiarity, but in
      a survey of 22 clinical pharmacologists in 12 countries of Europe, warfarin (57%)
      or phenprocoumon (24%) were the agents recommended most often in clinical
      practice.

PMID- 8269111
TI  - Left ventricular outflow tract: some lessons learned.

PMID- 8269112
TI  - Obstruction of the left ventricular outflow tract: anatomical observations and
      surgical implications.
AB  - Obstruction within the outflow tract from the left ventricle can take several
      anatomic forms. To understand better these substrates, we reviewed the anatomy in
      the normal heart and, with this background, focused on the malformations observed
      at each level of the outflow tract which produce stenosis. We examined 75
      malformed hearts and reviewed the literature pertinent to surgical aspects of
      obstruction. Close study of the normal aortic valve shows the lack of any
      discrete fibrous structure which can be described in terms of a ring-like
      annulus. The semilunar attachment of the leaflets makes a crown-shaped
      arrangement at the ventriculo-arterial junction rather than a strict ring. In the
      pathological study, valvar abnormalities were found in 45 cases. The valve had
      three leaflets in 20 cases, two leaflets in 24 cases and one leaflet in to the
      other. In two cases, additional obstruction was found at the sinutubular
      junction. Subvalvar stenosis was found in 30 hearts, the aortic valve being
      trifoliate in 28 and bifoliate in 2. The main substrate of subvalvar obstruction
      was posterior malalignament of the outlet septum (40%), followed by muscular
      septal hypertrophy (23%); obstruction was also an intrinsic feature in
      association with atrioventricular septal defects (14%). Although rare in our
      material, it can also be due to a fibrous or fibromuscular shelf. In our review
      of the literature, we have highlighted the various forms of valvar malformation
      and commented on the surgical options. Clear analysis of both the level of
      obstruction, and its precise anatomic substrate are essential for optimal
      surgical intervention.

PMID- 8269113
TI  - The investigation of a heart valve patient with suspected hypercoagulability.
AB  - A major complication associated with prosthetic heart valves is valve thrombosis
      and embolization. Depending on the valve design these complications should be
      almost eliminated by anticoagulants or aspirin. However, valve thrombosis and
      embolism may occur despite apparently adequate anticoagulation. The question is
      whether these thrombi arise as a result of local factors such as the foreign
      surface and disturbance of flow at the valve site, or as a result of alteration
      of the hemostatic balance within the blood favoring thrombus formation. Such a
      disturbance, known as hypercoagulability, is the result of increased platelet
      activation or coagulation, or diminished fibrinolytic activity. In this article
      the underlying mechanism of the coagulation and fibrinolytic mechanisms is
      discussed, with particular emphasis on the pathways, by which activation of the
      coagulation system or an increase in the inhibition of fibrinolysis might occur.
      The laboratory tests which might be useful in detecting platelet activation,
      activation of coagulation or fibrinolytic activity are discussed. The potential
      significance of raised blood viscosity associated with a rise in fibrinogen is
      emphasized, in particular the fact that elevated fibrinogen is a risk marker of
      many types of occlusive vascular disease. Whether raised fibrinogen is causal in
      the pathogenesis of thrombosis at the valve site, or merely is a consequence of
      the prosthesis, is not known. There is some information on the fact that patients
      with intracardiac, and left atrial thrombi in atrial fibrillation, have
      activation of coagulation as shown by elevated levels of markers and also raised
      von Willebrand factor levels. However, it is emphasized that large scale
      prospective studies, in which the risk markers are measured, and then the
      patients with prosthetic valves followed to determine whether or not they
      experience clinical embolic events has not been carried out. It is unlikely that
      a single hemostatic test, or indeed, a number of tests, will be able to predict
      with accuracy the individual who is at particular risk of embolism. Nevertheless,
      it is important that we seek to gain further information of the mechanisms of
      prosthetic valve thrombus formation, and then apply this knowledge in controlled
      clinical trials. Only this way will better anticoagulant and antithrombotic
      control of these devastating embolic events be achieved.

PMID- 8269114
TI  - The mitral valve apparatus: is there still room to doubt the importance of its
      preservation?

PMID- 8269115
TI  - Doppler-derived aortic valve gradients: imaging versus non-imaging techniques.
AB  - BACKGROUND: Quantitative Doppler echocardiography has become an established
      method for estimating aortic valve area in aortic stenosis, replacing cardiac
      catheterization as the confirmatory study. The technique is time consuming,
      especially when measuring the transaortic velocity, which is performed by
      convention. This is accomplished by interrogating multiple windows with a non
      imaging probe to record the maximal velocity. To determine how the examination
      could be expedited, we prospectively compared aortic valve gradients measured by
      Pedof and duplex transducers. METHODS: One hundred eighty-two consecutive
      patients with native aortic valve disease, mechanical or bioprosthetic aortic
      valves were studied. Two technicians measured maximal transaortic valve
      velocities from apical, subcostal, right parasternal and suprasternal notch
      windows with a 2 MHz Pedof probe and from the apical window with a 3-3.5 MHz
      duplex probe using color flow to orient the continuous wave beam. Angle-corrected
      and non-angle-corrected signals were recorded. There were 109 comparisons read by
      two observers; intra- and inter-reader variations were 0.4% and 2.0%,
      respectively. RESULTS: Duplex imaging velocity gradients were consistently
      smaller than Pedof non-imaging measurements with a mean +/- 1 standard deviation
      difference between peak velocities of 0.40 +/- 0.71 meters per second (m/s) for
      angle-corrected, and 0.76 +/- 0.68 for non-angle-corrected signals (both p <
      0.001). Technician variability accounted for some of the difference (p < 0.02).
      CONCLUSION: Although non-imaging and imaging methods share the apical window, the
      Pedof probe scans unlimited planes to locate the maximal aortic valve gradient,
      whereas the duplex probe is confined to the plane providing the optimal two
      dimensional image. Therefore, Doppler echocardiographic estimations of aortic
      valve areas still require careful, time-intensive non-imaging recordings of
      transaortic velocities.

PMID- 8269116
TI  - Significance of spontaneous echo contrast, or, does "smoke" indicate "fire"?

PMID- 8269117
TI  - Small abnormal echos after mitral valve replacement with bileaflet mechanical
      prostheses: predisposing factors and effect on thromboembolism.
AB  - Early transesophageal echocardiography (TEE) after mitral valve replacement can
      detect symptomless, non-obstructive thrombus on prosthetic valves and also small
      filamentous abnormal echoes (SAE). The object of this study is to evaluate their
      respective frequency and predisposing factors. Between October 1988 and June
      1992, 129 consecutive patients underwent mitral valve replacement with a
      bileaflet prosthesis and had transesophageal echocardiography at an average of 15
      +/- 7 days (range: 6-35 days) after surgery. Details of postoperative
      anticoagulation were analyzed in 99 patients from five surgical centers having
      comparable postoperative anticoagulation protocols. Among those patients
      presenting with SAE, 76% had a second transesophageal echocardiography at an
      average of 145 +/- 166 days after the first examination. Mean age was 56 +/- 13
      years. Small filamentous echoes were found in 55 patients (43%). In univariate
      analysis, independent predictors were age, absence of systolic regurgitation
      across the mitral prosthesis as observed with continuous Doppler, and the
      presence of spontaneous echo contrast (SC) in the left atrium: 54 +/- 14 years in
      the absence vs. 59 +/- 10 in the presence of SAE (p < 0.05); 54% of systolic leak
      vs. 36% (p < 0.05); 43% of SC vs. 75% (p < 0.00001). In multivariate analysis,
      spontaneous echo contrast was the only independent predictor for SAE (p <
      0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269118
TI  - Clinical implications of left atrial spontaneous echo contrast in mitral valve
      disease.
AB  - The aim of this study was to investigate the factors related to the presence of
      left atrial spontaneous echo contrast in mitral valve disease, and to ascertain
      whether it is a predictor of thromboembolism. One hundred and one patients (47
      men, 54 women) with a mean age of 57.04 +/- 10.6 years who underwent
      transthoracic and transesophageal echocardiography were included in the study.
      Forty-five (44.5%) had isolated or predominant mitral valve stenosis, 12 (11.9%)
      predominant mitral insufficiency and 44 (43.6%) had had previous mitral valve
      replacement. Left atrial spontaneous echo contrast was detected by
      transesophageal echocardiography in 58 patients, while the transthoracic approach
      detected it in only 15 (14.9%) (P < 0.0001). An atrial thrombus was found in six
      cases, with a history of recent systemic embolism in three of them. There was no
      thrombus in the left atria of a further nine patients, despite definitive
      histories of recent systemic embolism. The finding of left atrial spontaneous
      echo contrast was related to the presence of atrial fibrillation or enlarged left
      atrium, the severity of mitral stenosis and the absence of significant mitral
      insufficiency. Anticoagulant therapy was not significantly associated with
      spontaneous left atrial echo contrast, but a stepwise linear regression analysis
      showed that its presence was the only independent predictor of thromboembolism (p
      < 0.0001). We conclude that left atrial spontaneous echo contrast in mitral valve
      disease can be discovered mainly by transesophageal echocardiography, and is
      correlated with factors which are associated with low left atrial blood flow
      velocity such as atrial fibrillation, enlarged left atrium, mitral stenosis of
      increased severity and the absence of significant mitral insufficiency.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269119
TI  - Tricuspid regurgitation following mitral valve replacement: an echocardiographic
      study.
AB  - The development of late tricuspid regurgitation following mitral valve
      replacement is accompanied by a severe reduction in exercise capacity and a poor
      functional outcome. In this study, we compared the clinical and echocardiographic
      characteristics of two matched groups with (n = 13) and without (n = 13)
      clinically significant tricuspid regurgitation. The preoperative pulmonary artery
      pressures and symptom durations were similar, but tricuspid regurgitation at
      palpation was detected only in patients who later developed severe tricuspid
      regurgitation (5/13 vs. 0/13; p < 0.02). None of the patients had
      echocardiographic evidence of rheumatic tricuspid valve disease at the time of
      the study, but the tricuspid annular diameter (3.7 +/- 0.5 cm vs. 3.2 +/- 0.4 cm;
      p < 0.05) and right ventricular diameter (4.9 +/- 0.4 cm vs. 4.0 +/- 0.8 cm; p <
      0.01) were greater in patients who had developed severe late tricuspid
      regurgitation. Echocardiographic parameters of left ventricular function and
      Doppler estimated pulmonary artery systolic pressures were similar in the two
      groups, and no evidence of prosthetic dysfunction or aortic valve disease was
      found. These results imply that late tricuspid regurgitation following mitral
      valve replacement develops as a result of dilation of the tricuspid annulus
      associated with right ventricular decompensation. The persistence of uncorrected
      tricuspid incompetence would seem to be an important contributory factor, and its
      accurate detection and correction at the time of initial surgery may prove to be
      the most effective means of preventing the development of this important
      complication of mitral valve replacement.

PMID- 8269120
TI  - Doppler echocardiographic evaluation of St. Jude Medical valves in the tricuspid
      position.
AB  - Sixteen of 20 patients who underwent tricuspid valve replacement with a St. Jude
      Medical valve at our hospital were followed for three to 164 months. Doppler
      echocardiographic and cineradiographic examinations of the replacement device
      were performed in 13 patients. There were six males and seven females in the
      study, with a mean age of 41.9 years. A St. Jude Medical prosthesis had also been
      implanted in the mitral or mitral and aortic positions of eight of these thirteen
      patients. Ten patients had normally functioning valves in the tricuspid position
      and three were diagnosed as malfunctioning. The peak velocity in those patients
      with normally functioning tricuspid valves was 1.3 +/- 0.2 m/sec. The calculated
      peak and mean pressure gradients were 6.7 +/- 1.9 mmHg and 2.6 +/- 1.1 mmHg,
      respectively, and the mean pressure half-time was 120 +/- 22 msec. All normally
      functioning valves in the tricuspid position had peak velocities of less than
      1.55 m/sec, and peak and mean pressure gradients of less than 9.6 mmHg and 5
      mmHg, respectively, with the pressure half-time being less than 140 msec in all
      cases, except for one of the three Doppler studies performed in one patient.
      However, three Doppler studies performed in two patients with a malfunctioning
      tricuspid valve revealed peak velocities, peak and mean pressure gradients and
      pressure half-times which were above these values. After replacement of the
      malfunctioning valve, or thrombolysis, all of the Doppler-derived values returned
      to the range found in normally functioning valves.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8269121
TI  - Potential flaws in the assessment of minor cerebrovascular events after heart
      valve replacement.
AB  - The specificity and sensitivity of the questionnaire method, whether through
      direct contact or via mail, in collecting information on thrombosis, embolism and
      bleeding after heart valve replacement were assessed by a critical analysis of
      methods currently in clinical use. The 16 questions contained in the standard
      questionnaire of the Albert Einstein College of Medicine searching for transient
      events were put to 1000 apparently healthy individuals. Additional questions
      related to risk factors such as previous heart valve replacement, any existing
      heart disease, hypertension, diabetes or current anticoagulant treatment for any
      reason were also asked. The male/female ratio was 54.9/45.1, and the mean age was
      36.3 years with a range of 14-97 years. Eighty-five persons had one or more risk
      factors, 915 had none. A positive answer to at least one of the questions
      searching for TIA (transient ischemic attack) was given by 69.4% (n = 59) of
      those with, and by 54.8% (n = 501) without any risk factors. The total number of
      reported 'events' was 164 (1.93/person) for those with, and 1331 (1.45/person)
      for those without any risk factors. Four different follow up methods were applied
      to each of 123 patients after heart valve replacement: (a) regular follow up at
      an out-patient clinic, questionnaires sent at (b) six, (c) 18 and (d) 36 months
      after the start of the study. 57% of the transient and reversible events reported
      at the out-patient clinic were forgotten and not mentioned by the same patients
      in the 36 month questionnaire. One of the three permanent disabilities was also
      'forgotten'.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269122
TI  - Unexpected findings concerning thromboembolic complications and anticoagulation
      after complete 10 year follow up of patients with St. Jude Medical prostheses.
AB  - Five hundred and four St. Jude Medical valves (SJM) were implanted in 435
      patients between September 1978 and March 1982. There were 234 females and 201
      males with a mean age of 52.8 +/- 10.1 years (range 12-83 years), who underwent
      204 aortic, 163 mitral, 67 mitral plus aortic and one triple valve replacements.
      All patients were followed prospectively. Follow up was 100% complete and
      averaged 122.2 +/- 1.1 months for operative survivors. The total follow up for
      aortic patients was 1968.5, for mitral patients 1520.4, and for double valve
      replacement 573.9 pty. For the entire patient population the total follow up was
      4080.8 pty. Early mortality was 2% after aortic, 4.3% after mitral and 5.9% after
      mitral plus aortic valve replacement. There were 68 late deaths representing a
      linearized incidence of 1.37%/pty in the aortic, 1.71%/pty in the mitral and
      2.61%/pty in the double valve replacement groups. The corresponding cumulative
      survival after ten years at risk was 85% in the aortic, 78% in the mitral and 72%
      in the double valve replacement groups. The ten year event-free survival was 64%
      in the aortic, 57% in the mitral and 47% in the double valve replacement groups.
      The linearized incidence for thromboembolic events was 3.71%/pty taking all
      events into account, and 2.67%/pty taking only the first or most severe of
      several events into account for aortic, 5.1%/pty and 4.08%/pty for mitral, and
      6.62%/pty and 5.40%/pty for double replacements, respectively. There were two
      cases of valve thrombosis, both with proven inadequate anticoagulation. When the
      prothrombin times measured with the different thromboplastize used in this
      patient group were converted to INR, the so far homogeneous values could be
      separated into three groups: INR = 3.0 to 4.5, 2.5 to 3.2 and 1.8 to 2.7. Low INR
      values caused only a marginal increase in the rate of embolism but a highly
      significant decrease in the rate of bleeding. These results suggest that the
      generally recommended INR of 3.0 to 4.5 is too high for the SJM. A large,
      multicenter, prospective randomized study is therefore proposed to establish the
      safe INR levels with low intensity anticoagulation after SJM implantation.

PMID- 8269123
TI  - Experience with moderate intensity anticoagulation and aspirin after mechanical
      valve replacement. A retrospective, non-randomized study.
AB  - A selected group of patients who underwent valve replacement were analyzed to
      evaluate the feasibility, effectiveness and safety of combined treatment with
      moderate intensity anticoagulation plus aspirin. One hundred ninety-six patients
      who received a total of 204 mechanical valve prostheses between 1985 and 1991
      were selected according to rigid criteria. The prostheses included 124 valves of
      caged ball design, 62 St. Jude valves and 18 others. The follow up of the whole
      population was 581.8 patient years, with an average of 2.97 patient years, and
      was complete by the definition criteria. All patients received moderate intensity
      anticoagulation with acenocoumarol (target International Normalized Ratio 2.5 to
      3.5) and daily aspirin (100 mg or 325 mg). The incidence of thromboembolic events
      for the whole group was 3.26% per patient year, but only 1.6% in patients
      "compliant" with treatment. Preoperative embolism and non-compliance with
      treatment had a strong correlation with postoperative thromboembolism. The INR
      values had a strong correlation with both thromboembolic and hemorrhagic events.
      The incidence of serious hemorrhagic events was 4.12% patient years although only
      two cases (0.34%/pty) were fatal (cerebral hemorrhages). There was no difference
      in hemorrhagic incidence between patients receiving either 325 mg or 100 mg
      daily. A low incidence of thromboembolic complications was attained with the use
      of combined antithrombotic and antiplatelet therapy, even in the first generation
      caged ball type prostheses. However, the combination of moderate intensity
      anticoagulation with either 325 mg or 100 mg aspirin was associated with a risk
      of bleeding similar to high intensity anticoagulation alone. The risk of bleeding
      appeared to be greater in the presence of gastric pathology, and the combination
      of anticoagulants and aspirin should be avoided in patients with these
      conditions.

PMID- 8269124
TI  - Growth potential after root replacement of the right and left ventricular outflow
      tracts.
AB  - A successful operation for acute and severe aortic regurgitation after balloon
      valvuloplasty together with mitral regurgitation is described in a 9-month-old
      infant. Aortic root replacement was performed using a pulmonary autograft, while
      the right ventricular outflow tract was reconstructed with an interposed left
      atrial appendage posteriorly and a heterologous pericardial patch anteriorly.
      Mitral valve reconstruction was also effectively accomplished. This combination
      of right and left ventricular outflow tract reconstruction has a good potential
      for growth and may provide a solution for the future in infants.

PMID- 8269125
TI  - Suspension of the papillary muscles during valve replacement for mitral stenosis.
AB  - Of 94 patients who underwent intravalvular mitral valve replacement with
      CarboMedics bileaflet mechanical prosthesis, 10 presented with heavily calcified
      stenotic valves. After total excision of the mitral valve in these patients, both
      papillary muscles were reconnected to the annulus with Goretex sutures. Repeat
      cardiac catheterization was completed in six of these 10 patients two to 24
      months after surgery. Global and segmental left ventricular function was
      estimated using the MEDIS program (Thorax Centrum, Rotterdam) for analysis of
      left ventricular function. In five of the six patients re-examined, the ejection
      fraction was improved, the global ejection fraction increasing from 54% +/- 6% to
      63% +/- 10%. We conclude, even though the number of followed patients is
      extremely small, that mitral valve replacement with suspension of the papillary
      muscles is surgically feasible and has beneficial effects on the contractility of
      the left ventricle in patients with mitral stenosis.

PMID- 8269126
TI  - Doppler echocardiographic evaluation of the Bioflo pericardial bioprosthesis.
AB  - The Bioflo pericardial bioprosthesis was introduced to improve the durability of
      previous pericardial bioprostheses by means of a protective sheath of bovine
      pericardium around the stent. It has since been withdrawn from the market. Before
      its withdrawal, we studied 19 patients with mitral Bioflo valves (three of 25 mm,
      seven of 27 mm, eight of 29 mm, one of 31 mm) and 21 patients with aortic Bioflo
      valves (eight of 19 mm, nine of 21 mm, four of 23 mm) between two weeks and six
      months postoperatively, at which time all were in NYHA functional classes I or
      II. Standard Doppler echocardiographic measurements were taken to determine the
      effective orifice area of all valves, the peak and mean diastolic gradients
      across the mitral valves, and the peak and mean systolic gradients across the
      aortic valves. The smaller Bioflo valves performed poorly both in absolute terms
      and in comparison with other valves, presumably due to a reduction in the
      effective orifice area by the protective sheath. This finding should be borne in
      mind by the designers of future pericardial bioprostheses.

PMID- 8269127
TI  - Controversies in percutaneous balloon pulmonary valvuloplasty: timing, patient
      selection and technique.
AB  - Balloon valvuloplasty is currently the preferred therapeutic alternative to
      surgical valvotomy in selected patients with isolated congenital pulmonary
      stenosis. Not only does pulmonary valvuloplasty consistently afford safe and
      dramatic reduction of the valvular obstruction, it also produces less trauma and
      an equivalent sustained gradient relief when compared to surgical intervention.
      However, despite its established role, controversies persist in certain aspects
      of balloon pulmonary valvuloplasty (BPV). They include the timing of
      intervention, the suitability of certain valve morphologies and the choice of
      balloon techniques. Based on clinical experience, the following recommendations
      can be made: 1. BPV is currently recommended for moderate to severe pulmonary
      stenosis. Patients with mild stenosis are better served by conservative
      management and serial echocardiographic assessments. 2. Classic pulmonary
      stenosis is most suitable for BPV. However, patients with milder forms of
      dysplastic valves are still potential candidates for BPV. 3. Adequate dilatation
      with optimal relief of obstruction can be achieved with either the single or
      double balloon technique. Whether the Inoue or fixed-balloon system is used is a
      personal preference. Equally good results can potentially be obtained by either
      balloon design.

PMID- 8269128
TI  - Finite element analysis of the mitral valve.
AB  - A finite element model was developed to examine deformation and stress patterns
      in the mitral valve under systolic loading conditions. This is the first three
      dimensional finite element model of the mitral valve, incorporating all essential
      anatomic components, regional tissue thickness, collagen fiber orientation and
      related anisotropic material properties. A non-linear, transient, dynamic
      analysis was performed which included time-dependent loading, leaflet and chordal
      mass inertial effects and chordal element bi-linearity. The model was first
      analyzed without either annular or papillary muscle contraction and then with
      either or both. The hypothesis was that the combination of annular and papillary
      muscle contraction would have a beneficial effect on valve function. In all
      models, the computed anterior leaflet principal stresses were tensile and of
      greater magnitude than those in the posterior leaflet. The principal stress
      directions were observed to correlate well with collagen fiber orientation.
      Earlier leaflet coaptation was demonstrated with annular contraction, promoting
      valve closure, while papillary muscle contraction increased the stress on the
      chordae tendineae and both leaflets, tending to pull the latter apart. The
      combination of the two combined these effects, and showed the most even stress
      distribution. The effects of annular and papillary muscle contraction on valve
      function were shown to be beneficial by this model, and they can be further
      elucidated by varying the extent and timing of the individual contractions. This
      model can be used to examine the effects of pathologic changes, surgical
      manipulations and proposed material replacements. It can thus aid both the
      surgeon and the biomedical engineer in improving the materials and techniques
      available for the repair and/or replacement of mitral valve system components.

PMID- 8269129
TI  - Comments on "Non-destructive evaluation of prosthetic heart valves by holographic
      interferometry".

PMID- 8269130
TI  - Non-destructive evaluation of prosthetic heart valves by holographic
      interferometry.
AB  - Dysfunction of prosthetic heart valves is a common complication after heart valve
      replacement, affecting both biologic and mechanical prostheses. A preoperative,
      non-destructive test of each individual valve may help to prevent the
      implantation of a valve which has material weaknesses. To this end we developed a
      technique for testing heart valve prostheses by holographic interferometry. The
      advantage of this technique is that it provides a non-contact, non-destructive,
      highly sensitive three dimensional analysis of the valve under loading. Samples
      of several mechanical and biologic valve substitutes were investigated.
      Deformations of the valve, due to small pressure differences applied to the
      samples in a specially developed test chamber, were recorded by double exposure
      holography. A fringe pattern superimposed on the image of the valve reconstructed
      from the hologram clearly indicates the presence of even the slightest defect in
      the valve material. Our experimental results demonstrate the ability of non
      destructive holographic screening testing to detect defects or weaknesses which
      may potentially lead to dysfunction in replacement valves.

PMID- 8269131
TI  - Prosthetic valve function under simulated low cardiac output conditions:
      preliminary observations.
AB  - An experimental protocol was developed and a series of laboratory experiments
      started to assess the function and behaviour of replacement valves under
      simulated low cardiac output, that is low flow and low pressure conditions. The
      Helmholtz Institute's pulse duplicator (1) and instrumentation were carefully
      tuned in order to achieve accurate and reproducible delivery of the required
      extremely small stroke volumes. A pilot study was completed with 27 mm St. Jude
      Medical and CarboMedics bileaflet valves and Wessex porcine bioprostheses, three
      each, in the simulated aortic position. The results of these experiments suggest
      that the performances of the two bileaflet prostheses are inadequate if the flow
      is less than 2.0 l/min; the porcine bioprosthesis needs relatively low flow to
      start proper function, but its stenotic nature soon becomes apparent; increase in
      pressure without a corresponding increase in flow has a deleterious effect on
      valve performances by increasing regurgitation; increasing pulse rate is
      inversely correlated with valve efficiency; and there is no "all-or-none" cut off
      point between functional and non-functional situation for the tested devices;
      there is a semilogarithmic relation between increasing flow and valve
      performance. The clinical consequences are manifold and may be related both to
      the stabilization of circulation and to the increased thromboembolic risk during
      the early postoperative period.

PMID- 8269132
TI  - Endothelialization of mechanical heart valves in vitro with cultured adult human
      cells.
AB  - Previous studies have shown that in vitro endothelialization of synthetic
      vascular prostheses with cultured autologous cells leads to a reduction in their
      thrombogenicity. It is possible that pre-endothelialization of mechanical heart
      valve prostheses would have a similarly advantageous effect. In this study we
      have therefore investigated the possibility of creating an endothelium layer on
      mechanical heart valve prostheses by seeding in vitro with cultured adult human
      endothelial cells. After harvest, endothelial cells were cultured for two to
      three weeks before seeding of six valves (three Monostrut, three CarboMedics
      bileaflet) with 1.5-2 x 10(5) cells/cm2. The valves were then kept under culture
      conditions for seven days. A confluent lining of cultured endothelial cells was
      observed in the scanning electron microscope on the parts covered with pyrolitic
      carbon, e.g. disc, leaflet, flange, and on carbon coated sewing rings. Untreated
      sewing rings showed a discontinuous endothelial lining. On the metallic surface
      only a few scattered cells were observed. Two endothelialized bileaflet valves
      were implanted in the mitral position in pig and permitted to perform physiologic
      work for one hour. A mainly continuous endothelium remained on the carbon covered
      sewing rings but the endothelium detached from the leaflets and flanges. This
      study demonstrates that mechanical heart valves do not contain cytotoxic
      compounds. It also demonstrates that cultured adult human endothelial cells are
      able to form a monolayer when seeded on monostrut and bileaflet valve prostheses.
      A significant number of cells remain on the sewing ring after pulsatile flow in
      the mitral position but not on the polished pyrolitic carbon surfaces.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269133
TI  - Fracture of the wire stent in a Carpentier-Edwards porcine bioprosthesis.
AB  - A 60-year-old woman underwent mitral and aortic valve replacement with Carpentier
      Edwards supra-annular bioprosthesis in 1986. Six years later rapidly progressing
      exercise dyspnea and orthopnea made hospital admission necessary. At chest x-ray
      and cardiac catheter examination one of the wire struts of the mitral
      bioprosthesis was found completely broken causing cusp prolapse. Surgical
      findings at reoperation confirmed the diagnosis. No apparent cause of the stent
      fracture was found.

PMID- 8269134
TI  - Reply to correspondence on randomization in surgical studies.

PMID- 8269135
TI  - Reflections on the pulmonary autograft.

PMID- 8269136
TI  - Pulmonary autograft--past, present, and future.

PMID- 8269137
TI  - The Ross procedure in a young rheumatic population: early clinical and
      echocardiographic profile.
AB  - The use of pulmonary autografts for aortic valve replacement is nearing its third
      decade. It is showing promise as a permanent aortic valve with its ability to
      grow with age. We report our experience of 45 patients with a mean age of 16.89
      years over a three year period. Rheumatic heart disease was the cause of aortic
      valve dysfunction in 38 (84.4%) patients. Sixteen (35.5%) patients also underwent
      mitral valve repair. Echocardiographic examination revealed early reduction of
      aortic regurgitation and left ventricular dimensions, which remained stable in
      the short follow up period. There were no early or late deaths. One patient
      required reoperation for a regurgitant pulmonary autograft at two years. We
      conclude that pulmonary autograft transplantation to the aortic root seems to
      offer a near permanent solution in a young population affected by rheumatic valve
      disease.

PMID- 8269138
TI  - Aortic infective endocarditis managed by the Ross procedure.
AB  - The excellent clinical results with homografts inserted for aortic endocarditis
      encouraged us to take this method one step further, believing that the placement
      of a pulmonary autograft which is totally viable and antibiotic-perfused would be
      an even better choice for valve replacement. We applied this technique in 13
      consecutive patients with infective aortic endocarditis, achieving excellent
      early results. Our follow up extending to 30 months continues to show excellent
      results with 0% re-infection and 0% mortality. We conclude from our experience
      that this technique affords excellent results in curing the infection with the
      lowest chance of thromboembolism, the lack of need for anticoagulation and only a
      small chance of reoperation in the future.

PMID- 8269139
TI  - Aortic valve implantation techniques--should they be any different for the
      pulmonary autograft and the aortic homograft?

PMID- 8269140
TI  - Partial inclusion aortic root replacement with the pulmonary autograft valve.
AB  - The expanded use of autografts for aortic valve replacement has focused attention
      on developing an improved implantation technique with the aim of reducing the
      incidence of early insufficiency. While the technique for total root replacement
      with nonstented tissue valves is a proven and established method, it is, however,
      not generally accepted for use in all clinical circumstances. Through the use of
      a partial inclusion technique, we propose to modify the standard method of
      extended aortic root replacement and pedicle coronary implantation. This approach
      also has the advantage of leaving the recipient aortic root intact. Unlike
      traditional scalloped subcoronary homograft implantation, it does not enclose the
      transplanted valve totally within the recipient aorta. Thus, there is
      preservation of the patient's aorta without distortion of the transplanted valve
      which occurs when it is forced completely into the closed recipient aortic root.
      While this partial inclusion method is not as simple as total root replacement,
      preservation of the recipient root is generally more acceptable to implanting
      surgeons. Either perfection of this proposed method or the acceptance of a
      traditional extended aortic root replacement will result in correction of the
      persistent problem of early aortic insufficiency following the use of autograft
      valves. Decreasing valve incompetence will have the desired effect of increasing
      the indication for the use of autografts for aortic valve replacement in young
      patients.

PMID- 8269141
TI  - Thromboembolic events in prosthetic valve recipients: what is the safe level of
      anticoagulation?

PMID- 8269142
TI  - Guidelines for prevention of thromboembolic events in valvular heart disease. Ad
      Hoc Committee of the Working Group on Valvular Heart Disease, European Society of
      Cardiology.

PMID- 8269143
TI  - German experience with low intensity anticoagulation (GELIA): protocol of a multi
      center randomized, prospective study with the St. Jude Medical valve.

PMID- 8269144
TI  - Long term survival without anticoagulation after aortic valve replacement with a
      Lillehei-Kaster prosthesis. A case report.
AB  - A patient who underwent aortic valve replacement with a Lillehei-Kaster
      prosthesis developed an early duodenal ulcer requiring suspension of warfarin
      treatment. Subsequently he was managed without oral anticoagulants, receiving
      only antiplatelet agents, starting from the third postoperative year. Neither
      thromboembolic nor hemorrhagic complications occurred but at reoperation,
      performed almost 20 years later for prosthetic stenosis caused by a fibrous ring,
      and aneurysm of the ascending aorta, mild fresh thrombus was found on the
      prosthetic ring. Although the long term outcome of patients with a mechanical
      aortic prosthesis can occasionally be successful even without long term
      anticoagulation, such management appears to be justified only in highly selected
      cases.

PMID- 8269145
TI  - Will randomized trials detect random valve failure? Reflections on a recent FDA
      workshop.

PMID- 8269146
TI  - Prognosis of valve replacement for aortic stenosis with or without coexisting
      coronary heart disease: a comparative study.
AB  - Between January 1978 and June 1992, 798 patients underwent isolated AVR for
      hemodynamically significant calcific aortic stenosis. Preoperative coronary
      angiography was performed in 687 patients, of whom 229 had coronary stenosis >
      40% and were divided into three (I, IIa and IIb) groups. Group I consisted of 144
      patients undergoing AVR plus coronary artery bypass grafts (CABG); 39 patients in
      Group IIa had AVR only in the presence of coronary stenoses < 60%, and 46
      patients in Group IIb had AVR only in the presence of coronary stenoses > 60%.
      Group III consisted of 144 matched patients selected from the remaining 458
      patients with no coronary disease, or stenoses less than 40%, according to five
      matching criteria (age, sex, functional status, ejection fraction and year of
      surgery) with patients in Group I. Early mortality was 10.4% in Group I, 7.7% in
      Group IIa, 13% in Group IIb and 4.9% in Group III. Although the differences in
      operative mortality are apparent, they did not reach statistical significance. A
      difference in long term survival could only be detected between Groups I and III
      (actuarial survival at nine years 66% and 78.9%, respectively, p < 0.01).
      Similarly, late coronary events were more frequent in Group I than in Group III
      (13.9% vs. 5.1%, p < 0.03). It is concluded that revascularization should be as
      complete as possible for severe coronary stenoses coexisting with significant
      calcific aortic stenosis. However, bypassing of moderate coronary lesions
      (stenoses in the order of 50%) in association with AVR does not appear justified
      on current evidence. Further studies on this important aspect are clearly
      required.

PMID- 8269147
TI  - Non-destructive evaluation techniques for prosthetic heart valves based on
      hologram interferometry. Part I.
AB  - The development of a technique applying hologram interferometry, which is a non
      destructive, non-contact, full-field, highly sensitive method is reported. The
      valve under investigation is placed in a test chamber which has windows providing
      optical access. Deformations of the valve leaflets due to pressure loading are
      recorded by hologram interferometry. The resulting interferogram clearly
      indicates the existence of any defects or structural anomalies which may be
      present in the valve material. Three modifications to this technique, intended
      for qualitative and quantitative non-destructive valve screening tests are
      described. The proposed technique is expected to become an effective means of
      detecting hidden defects of replacement heart valves; it is thus considered as a
      prospective tool for quality control, particularly in the manufacture of
      bioprosthetic valves, where initial sites of late calcification and degeneration
      might be identified. The application of holographic non-destructive testing may
      therefore substantially improve the quality and durability of heart valve
      substitutes.

PMID- 8269148
TI  - Non-destructive evaluation techniques for prosthetic heart valves based on
      hologram interferometry. Part II: Experimental results and clinical implications.
AB  - Non-destructive evaluation by hologram interferometry of seven mechanical and
      seven bioprosthetic valves was carried out. Irregular fringe patterns suspect of
      intrinsic valve anomaly which may lead to later dysfunction were detected in one
      mechanical and six bioprosthetic valves. Histologic examination of two
      bioprosthetic valves revealed focal degeneration, especially in the fibrosa, in
      those parts of the leaflets that had obvious anomalies on the holographic
      interferograms. It was shown that the flow turbulences caused by prosthetic
      valves can also be evaluated using hologram interferometry. The experimental
      results, obtained with six different types of prostheses (Lillehei-Kaster, Bjork
      Shiley, Omnicarbon, St. Jude Medical, Carpentier-Edwards S.A.V. and Valcor),
      demonstrated the applicability of this technique to both mechanical and
      bioprosthetic valves. Carrying out non-destructive screening tests for heart
      valve prostheses may prevent the implantation of potentially dysfunctional
      devices.

PMID- 8269149
TI  - Assessing the severity of aortic valve stenosis by spectral analysis of cardiac
      murmurs (spectral vibrocardiography). Part I: Technical aspects.
AB  - Assessing the severity of aortic stenosis remains an important clinical problem.
      The turbulent pressure fluctuations generated by the confined jet down-stream of
      the stenotic valve produce vibrations in the aortic wall. These vibrations are
      transmitted through the chest to the skin surface, where they can be measured as
      systolic ejection murmurs. The purpose of the present study was to find the
      relationship between the severity of aortic valve stenosis and the frequency
      content of the precordial systolic murmurs, and to evaluate the transthoracic
      attenuation of murmurs and its variation from patient to patient. Twenty-four
      patients with clinical signs of aortic stenosis underwent cardiac catheterization
      to measure the peak transvalvular pressure difference. The mean energy density
      spectrum of the measured systolic precordial murmurs was calculated and the
      murmur energy ratio between 100-500 Hz and 20-500 Hz was correlated to the
      transvalvular pressure difference. The inter-individual variability of the
      transthoracic attenuation was evaluated by calculating the transthoracic transfer
      function from simultaneous measurements of precordial vibrations at the second
      right intercostal space and intravascular recordings of high frequency pressure
      fluctuations in the ascending aorta. The transvalvular pressure difference and
      the square root of the murmur energy ratio correlated well (r = 0.81, SEE = 27
      mmHg). In the frequency range from 10-500 Hz the transthoracic transfer function
      could be modelled by a low-pass filter function with a low frequency attenuation
      of 36 +/- 7.7 dB (mean +/- SD), a corner frequency of 26 +/- 12 Hz and an
      attenuation slope of -29 +/- 7.9 dB/decade. Spectral analysis of systolic murmurs
      might be an attractive non-invasive addition to the array of techniques already
      in use for assessing the severity of aortic stenosis. It is a simple and cost
      effective technique, and requires less skill and time for data analysis than
      conventional methods.

PMID- 8269150
TI  - Assessing the severity of aortic valve stenosis by spectral analysis of cardiac
      murmurs (spectral vibrocardiography). Part II: Clinical aspects.
AB  - Assessing the severity of aortic stenosis remains an important clinical problem.
      The turbulent pressure fluctuations generated by the jet downstream of the
      stenotic valve produce vibrations in the aortic wall. These vibrations are
      transmitted through the chest to the skin surface, where they can be recorded as
      systolic ejection murmurs. The purpose of the present study was to estimate the
      transvalvular aortic pressure difference by spectral analysis of heart murmurs
      (spectral vibrocardiography). Forty-four patients with clinical signs of aortic
      stenosis underwent cardiac catheterization to measure the transvalvular pressure
      difference. In a double blind prospective study, precordial vibrations were
      measured prior to catheterization using a dedicated heart sound analyzer
      (Vibrocard 2000) to calculate the spectral ratio of murmur energy between 100-500
      Hz and 20-500 Hz. Three different weighting filters were used to compensate for
      individual differences in the transthoracic attenuation of murmurs. The square
      root of the murmur energy ratio correlated linearly with the mean transvalvular
      pressure difference (r = 0.80, SEE = 13 mmHg) and with the peak transvalvular
      pressure difference (r = 0.81, SEE = 16 mmHg). The use of individual compensation
      filters improved the correlation. This study shows that it is possible to
      estimate the transvalvular pressure difference in patients with aortic valve
      stenosis by spectral analysis of heart murmurs. It is a fast, simple and cost
      effective technique, which requires less skill than conventional methods.

PMID- 8269151
TI  - The management of severe adherence of mediastinal structures to the sternum
      during cardiac reoperations.
AB  - The author's method for sternal re-entry in cases of extremely dense mediastinal
      adhesions is described. The anterior lamina and the spongiosa of the sternum is
      cut with an osteotome and the posterior lamina is divided using the Lebsche knife
      so as to leave the densely adhered patch of the posterior lamina on the
      underlying soft tissue. These bone fragments may be left in loco or, if the
      course of the operation requires it, they may be gently raised and peeled off.
      Removal of such a portion or portions of the posterior lamina does not
      appreciably weaken the sternum and safe sternal closure may be accomplished
      without difficulty.

PMID- 8269152
TI  - Corrected transposition of the great arteries. Repair of regurgitant tricuspid,
      mitral and pulmonary valves.
AB  - A 68 year old male patient with corrected transposition of the great arteries in
      situs solitus (SLL) underwent successful repair of regurgitant tricuspid, mitral
      and pulmonary valves. An aneurysm of the pulmonary artery, found incidentally
      during surgery, was also repaired.

PMID- 8269153
TI  - Aorto-left atrial fistula in prosthetic aortic endocarditis.
AB  - Aortic valve endocarditis commonly leads to the formation of a root abscess, but
      fistulae are uncommon. The echocardiographic findings in a patient with
      Streptococcus viridans endocarditis of a prosthetic aortic valve associated with
      a fistula between the aorta and the left atrium are presented. The diagnosis was
      made by transthoracic echocardiography, although the transesophageal study gave
      higher resolution views and allowed a more confident exclusion of mitral valve
      involvement.

PMID- 8269154
TI  - Late outcome of valve replacement with the Cross-Jones caged-lens prosthesis.
AB  - A 58 year old woman underwent re-replacement of a Cross-Jones caged-lens mitral
      prosthesis 23 years after the first operation. She represented one of the 38
      patients who received 42 Cross-Jones prostheses two decades earlier. Continued
      adequate performance for more than two decades in five patients bears a
      surprising testimony to the longevity of this historic low profile prosthesis.

PMID- 8269155
TI  - In response to: Gometza B, Kumar N, Prabhakar G, Galio R, Kandeel M, Duran CMG.
      The challenge of valve surgery in a developing population.

PMID- 8269156
TI  - Prediction of valve failure: statistical modelling and pattern recognition.

PMID- 8269157
TI  - Utilization of manufacturers' implant card data to estimate heart valve failure.
AB  - Heart valve manufacturers possess the most complete inventory of world-wide
      mechanical valve failures, but to convert failures to time-related risks requires
      estimates of patient follow up. Since manufacturers did not actively track
      patients, they needed a model that incorporates an assumed death rate to decrease
      the numbers of patients at risk. We present a method for using a manufacturer's
      implant card database to estimate time-related complication rates for patient
      subsets, and illustrate its use by examining the risk of outlet strut fracture
      (OSF) with the Bjork-Shiley 60 degrees Convexo-Concave valve (CC60). We developed
      a parametric model for valve patient survival based on actively followed valve
      patients from three centers using only variables typically available from implant
      cards. Using this survival model, a simulated lifetime was produced for each
      valve in the CC60 implant database for which the required covariates were known.
      These lifetimes were then used to analyze OSF as if they were true follow up
      times. This allowed the use of conventional methods of univariate and
      multivariate analysis for OSF, including parametric statistical models. According
      to the approximate linearity of the cumulative hazard functions, OSF risk over
      time appeared to be fairly constant. Several risk factors were identified,
      including valve size, patient age at implant and valve position. Using parametric
      models for both patient survival and OSF permits the estimation of the
      probability of OSF before death for an individual patient (as opposed to the
      usual actuarial probability of OSF given that the patient does not die). Because
      the patient may die before his valve would have failed, this cumulative incidence
      of OSF is always less than the actuarial risk. For all but the very highest risk
      patients, the cumulative incidence over their relatively short remaining
      lifetimes is very small.

PMID- 8269158
TI  - Prediction of valve-related complications for artificial heart valves using
      adaptive neural networks: a preliminary study.
AB  - A novel approach to the prediction of valve-related complications in patients
      with implanted artificial heart valves is discussed. Adaptive artificial neural
      networks were used to identify patients at high risk of valve-related events
      based on preoperative data. Data from a clinical trial on 789 subjects with
      Carpentier-Edwards pericardial bioprostheses were used. Patients' records were
      divided into two groups, one of which was used for training the neural network
      and the other for testing the trained network and determining error rates.
      Patient information such as age, sex, NYHA class and anticoagulation therapy, as
      well as valve information such as size and the date of implant, were used as the
      network inputs. The neural net had a single output variable indicating the risk
      that an individual patient would develop a valve-related complication resulting
      in death. The results show that a trained neural network was able to predict
      valve-related deaths in the specified time interval of 1981-1991 with a high
      degree of accuracy. The neural network was also successful in classifying
      patients into high and low risk categories.

PMID- 8269159
TI  - Acute mitral regurgitation.

PMID- 8269160
TI  - Diagnostic and therapeutic considerations in acute, severe mitral regurgitation:
      experience in 42 consecutive patients entering the intensive care unit with
      pulmonary edema.
AB  - Forty-two consecutive patients received emergency treatment for acute mitral
      insufficiency causing pulmonary edema between 1984 and 1992. The underlying
      diagnoses were acute myocardial infarction (n = 21), acute bacterial endocarditis
      on the native mitral valve (n = 9), prosthetic endocarditis in the mitral
      position (n = 4), acute failure of a replacement valve (n = 5), blunt chest
      trauma (n = 1) and chordal rupture in Marfan's syndrome (n = 2). Dysfunction of
      the subvalvular apparatus was present in 24 patients, verified by transthoracic
      echocardiography in 18 (75%) and by transoesophageal echocardiography in all
      patients in whom this technique was used. There were four cases of outflow strut
      fracture of a Bjork-Shiley mitral prosthesis; a reliable diagnosis was made by
      fluoroscopy in all patients. Bedside hemodynamic monitoring was found to be
      unreliable both for differential diagnosis and for the quantitative assessment of
      the degree of mitral insufficiency. The right ventricular filling pressure was
      normal in 32/39 patients (82%), and the pulmonary artery and pulmonary capillary
      pressures elevated in 37/39 (95%). Diagnostically important, high pulmonary
      capillary v-waves were documented in 13 patients (33%). The left ventricular
      impedance could be influenced with sodium nitroprussid combined in some cases
      with dobutamin, and the resultant decrease of the peripheral vascular resistance
      from 1480 +/- 222 to 702 +/- 86 dyn x sec x cm-5 was followed by a proportionate
      reduction in the transmitral regurgitant fraction. Three patients died prior to
      the intended emergency surgical intervention. Emergency surgery was completed in
      21 patients with an early mortality of 23.8% (n = 5). Ten patients underwent
      elective surgery within, and another three later than one year from the onset of
      the acute symptoms with an early mortality of 7.7% (n = 1). Four patients are
      alive and clinically well with medical treatment alone.

PMID- 8269161
TI  - Emergency surgical treatment of ruptured incompetent mitral valve after
      percutaneous valvuloplasty.
AB  - Of 263 consecutive patients undergoing mitral balloon valvulotomy at the Cardiac
      Catheterization Unit of Padua University Hospital, six (2.3%) required surgical
      treatment within 24 hours. The indication for surgery was unstable hemodynamic
      status due to acute mitral insufficiency caused by the percutaneous balloon
      valvulotomy. The purpose of this study was to evaluate whether the failure of
      percutaneous mitral balloon valvulotomy, in this subset of patients, was related
      to technical problems or was the direct consequence of unfavourable pathologic
      conditions. Additionally, we evaluated the operative results and clinical outcome
      of these six patients. The patients were all female with a mean age of 55.7 +/-
      14 years (range 38-75 years). Previous surgical commissurotomy was performed in
      three. The anatomical lesions responsible for the massive regurgitation were tear
      of the anterior leaflet in two patients and tear of the posterior leaflet in
      four; rupture of the papillary muscle and/or chordae tendineae were present in
      five. All patients underwent mitral valve replacement. The elapsed time between
      the onset of mitral regurgitation and surgery ranged from two to 24 hours (mean
      10 +/- 11 hours). There were two hospital deaths (33.3 +/- 21.1%): all surviving
      patients are alive and clinically well. In conclusion, massive mitral
      regurgitation following percutaneous mitral dilatation appears to be related to
      unfavourable pathology of the mitral valve rather than to technical errors.
      Therefore, careful patient selection is mandatory in order to achieve optimal
      results. In our experience, adequate and aggressive medical therapy provided
      sufficient time to prepare for the surgical intervention.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8269162
TI  - Mitral regurgitation from papillary muscle rupture: role of transesophageal
      echocardiography.
AB  - A case of a 61 year old male with lateral myocardial infarction, congestive heart
      failure and fever of days is presented. The exact etiology of this patient's
      heart failure was established with the application of transesophageal
      echocardiography. The transthoracic two-dimensional and Doppler echo showed a
      mobile echogenic density attached to the tip of the anterior mitral leaflet
      accompanied by moderate mitral regurgitation. Transesophageal echocardiography
      attributed this echogenic density to a ruptured head of the anterolateral
      papillary muscle, resulting in severe mitral regurgitation. Cardiac
      catheterization confirmed the severe mitral regurgitation and uncovered
      significant stenotic lesions of the coronary arteries. The resultant surgical
      treatment for the replacement of the mitral valve and coronary artery by-pass
      confirmed the rupture of the head of the anterolateral papillary muscle. It is
      suggested that transesophageal echocardiography is particularly capable of
      providing a definitive and prompt diagnosis of papillary muscle rupture.

PMID- 8269163
TI  - Improving surgical strategies for ischemic mitral regurgitation.

PMID- 8269164
TI  - Ischemic mitral regurgitation: when and how should it be corrected?
AB  - True and significant ischemic mitral regurgitation affects on average 4% of the
      patients undergoing coronary bypass surgery. It not corrected, it profoundly
      influences the hospital mortality and the five year survival, even in the case of
      satisfactory myocardial revascularization. It is found predominantly in cases of
      right coronary and/or circumflex disease, and results mostly from restricted
      leaflet motion rather than from prolapse. Mitral annulus dilatation is present in
      all cases, and is the only mechanism of regurgitation in 50% of the patients. The
      indication for a valve procedure usually rests on findings at heart
      catheterization (i.e. the ratio of regurgitant/forward stroke volume, LV end
      systolic volume index), but may be refined by pre- and perioperative
      transesophageal echocardiography; the LV volume loading test is very helpful in
      taking the decision in case of moderate or intermittent regurgitation. Mitral
      valve annuloplasty will easily and expeditiously correct or decrease the
      regurgitation in the majority of cases. If the mitral valve has to be replaced,
      the surgeon should always try to keep the papillary muscle-annulus continuity, at
      least posteriorly.

PMID- 8269165
TI  - Mitral valve prolapse: left ventricular hemodynamics in patients with chest pain,
      dyspnea or both.
AB  - Patients with mitral valve prolapse may present with chest pain and dyspnea. Left
      ventricular hemodynamics as a cause for these symptoms have not been completely
      evaluated in these patients. The present study was undertaken to investigate left
      ventricular hemodynamics in symptomatic patients with mitral valve prolapse. One
      hundred and three patients with mitral valve prolapse (female 72, male 31, age 56
      +/- 11 years) had diagnostic cardiac catheterization for evaluation of chest pain
      (n = 44), dyspnea (n = 10) and for chest pain plus dyspnea (n = 49). All patients
      had diagnostic auscultatory findings and angiographic documentation of mitral
      valve prolapse. Patients with coronary artery disease and mitral regurgitation
      greater than mild were excluded from the study. Left ventricular end diastolic
      pressures before (chest pain 9.3 +/- 3.7 mmHg; dyspnea 8.2 +/- 4.2 mmHg; chest
      pain plus dyspnea 9.3 +/- 4.1 mmHg) and after left ventriculography (chest pain
      11.6 +/- 5.5 mmHg; dyspnea 10.2 +/- 2.3 mmHg; chest pain plus dyspnea 11.7 +/-
      5.6 mmHg) were normal in the majority of patients and similar in all three
      groups. Likewise, the left ventricular end diastolic volume index (chest pain
      72.0 +/- 16 cm3, dyspnea 69.1 +/- 20 cm3, chest pain plus dyspnea 70.0 +/- 16
      cm3) and ejection fraction (chest pain 64.0 +/- 8.4%, dyspnea 64.1 +/- 6.1%,
      chest pain plus dyspnea 64.3 +/- 6.1%) were normal in the majority of patients
      and similar in the three groups. Symptomatic patients with mitral valve prolapse
      without significant mitral regurgitation had normal left ventricular
      hemodynamics, and their symptoms cannot be explained on the basis of hemodynamic
      abnormalities alone.

PMID- 8269166
TI  - Aortic valve replacement in the elderly.
AB  - Aortic valve replacement is an established mode of therapy that enhances and
      prolongs life in patients with significant aortic valve disease. This is true for
      the elderly, but with a higher reported mortality and morbidity than in younger
      patients. One hundred and eighty-three elderly patients aged 70 years and over
      were considered suitable candidates for isolated aortic valve replacement (n =
      97) or aortic valve replacement combined with coronary artery bypass surgery (n =
      86) in the decade 1980-89. The mean age at surgery was 73.2 years (70-80). The
      hospital mortality and morbidity of this group were compared to 340 consecutive
      patients aged 60-69 who underwent similar surgery over the same period. There was
      no significant difference in hospital mortality: 4.4% for elderly patients and
      4.1% for those aged 60-69. Measures of hospital morbidity were similar except for
      the perioperative stroke rate, which was 4.4% in the elderly patients and 1.5% in
      the younger group (p < 0.05). Detailed long term follow up was obtained in 75 of
      the 76 elderly patients who underwent aortic valve replacement or aortic valve
      replacement combined with coronary artery bypass surgery in the first five year
      period. Hospital survival was 99% (one hospital death). The overall five year
      actuarial survival was 81% and greater than the age and sexmatched general
      population (73%). Of the 44 patients alive at the time of review, 35 (80%) were
      free of angina and 32 (73%) had no significant symptoms of heart failure.
      Additionally, these patients were questioned about their quality of
      life.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269167
TI  - Aortic annular abscess complicating prosthetic valve endocarditis with group G
      streptococcus: detection during life with transesophageal echocardiography.
AB  - Infection with group G streptococcus is an unusual but virulent cause of
      endocarditis. Aortitis and abscess formation due to this organism have been
      described in one previous report, but only at necropsy. We present here a patient
      with group G streptococcal endocarditis and aortic annular abscess diagnosed
      during life by transesophageal echocardiography, leading to successful surgical
      intervention.

PMID- 8269168
TI  - Surgery for organic rheumatic disease of the tricuspid valve.
AB  - The paucity of reports on the incidence and management of organic involvement of
      the tricuspid valve in rheumatic disease led us to carry out this retrospective
      study. Over a four and a half year period, of the 1052 patients undergoing valve
      surgery at our institution, 253 (24.05%) required tricuspid surgery. Organic
      involvement was noted in 115 (45.45%) of these patients. Definitive preoperative
      diagnosis was feasible by echocardiogram in only 48 (41.73%). Tricuspid
      regurgitation was present in all patients while detectable stenosis was present
      in 48 (41.7%). Annular dilatation was seen in 52 (45.2%). Primary repair was
      possible in 107 patients (93.0%). The reduction in tricuspid regurgitation
      remained stable at the last follow up in all but seven patients. Nine patients
      underwent reoperation in this study for failure of left-sided valve repairs, of
      which five needed reoperation on the tricuspid valve. All the five reoperated
      tricuspid valves had had dilated annuli at primary surgery. The presence or
      absence of annular dilatation did not cause any significant difference in early
      or late mortality. The presence of annular dilatation in the presence of left
      sided valve lesions superimposed on organically involved tricuspid valves evokes
      the possibility of the presence of an organo-functional disease.

PMID- 8269169
TI  - Tricuspid valve endocarditis: repair with the use of artificial chordae.
AB  - We report on a patient who developed tricuspid valve endocarditis on a permanent
      endocardial pacemaker lead. At operation the endocardial lead was removed and
      accurate debridement of the tricuspid tissue was performed. Tricuspid valve
      reconstruction included commissural plication and the construction of artificial
      polytetrafluoroethylene chordae from the anterior leaflet to the anterior
      papillary muscle to obtain valve competence.

PMID- 8269170
TI  - Mitral pressure half-time: is it a valid measure of orifice area in artificial
      heart valves?
AB  - The Hatle orifice area formula was derived in patients with significant mitral
      stenosis and was not intended for use in other situations. Comparisons between it
      and other methods of estimating orifice area have shown variability in the slope
      of the regression lines with wide dispersal of data points. There is no
      relationship in prosthetic valves between pressure half-time and annulus
      diameter. Pressure half-time is determined by a number of factors other than
      orifice area, notably left ventricular compliance, the square root of the peak
      transmitral pressure drop at the start of diastole, and stroke volume. In normal
      prosthetic valves, therefore, pressure half-time reflects non-prosthetic factors
      more accurately than orifice area, and other formulae, such as the continuity
      equation, should be used to assess the latter. A pressure half-time prolonged
      beyond 200 ms remains a useful indication of obstruction, especially when the
      peak transmitral velocity is high.

PMID- 8269171
TI  - Clinical relevance of the low correlations between Doppler and hemodynamic
      measurements before and after balloon mitral commissurotomy.
AB  - The aim of this study was to evaluate the clinical consequences of the poor
      correlations between Doppler and hemodynamic measurements before and after
      balloon mitral commissurotomy (BMC). From March 1987 to December 1991, 317
      patients with symptomatic mitral stenosis were selected for BMC at the Montreal
      Heart Institute. Despite the low correlation coefficients between Doppler and
      hemodynamic measurements before BMC (transmitral gradient: r = 0.57, mitral valve
      area: r = 0.35, mitral regurgitation: r = 0.33), the positive predictive value of
      Doppler echocardiography to select patients for BMC was 96%. Hemodynamic success,
      defined as a final mitral valve area greater than 1.5 cm2 and an increase in
      mitral valve area of more than 25% was obtained in 204 (80%) of the 253 patients
      who completed the procedure without complications. Doppler and hemodynamic mitral
      valve area increase were poorly correlated (r = 0.2) but the sensitivity and
      specificity of Doppler in the diagnosis of hemodynamic success were 86% and 63%
      respectively. A prospective six month echocardiography and hemodynamic re
      examination was performed in our 50 patients first treated by BMC. Hemodynamic
      restenosis, defined as a loss of more than 50% of the gain achieved in mitral
      valve area and a mitral valve area of less than 1.5cm2 were diagnosed in 12 (26%)
      of the 46 patients with initially successful BMC. Despite a low correlation
      between Doppler and hemodynamic mitral valve area measurements (r = 0.28), the
      sensitivity and specificity of echocardiography in the diagnosis of hemodynamic
      restenosis were 66% and 88% respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269172
TI  - Semiquantitation of aortic regurgitation by pulsed Doppler examination of the
      subclavian artery velocity contour.
AB  - The reflux of aortic regurgitation causes an increased and longer diastolic
      reverse flow in the aorta and its branching vessels as compared to the normal
      flow contour. The changes of the aortic flow are related to the severity of
      aortic regurgitation and can be demonstrated by Doppler ultrasound. As Doppler
      examinations are often restricted in the aorta, a prospective study was designed
      to determine the feasibility and accuracy of Doppler measurements in the
      subclavian artery for the identification of severe forms of aortic regurgitation.
      Fifty-five patients with and 40 patients without aortic regurgitation were
      examined both by aortography and pulsed Doppler flow analysis of the subclavian
      artery. Two age groups were differentiated: patients below and those over 60
      years of age, respectively. A high quality Doppler signal was recorded in all
      patients. In patients below 60 years, the best predictors of severe aortic
      regurgitation proved to be a pandiastolic reverse flow and an increased
      regurgitant fraction (77%) with a sensitivity of 100% and specificity of 75% and
      92%, respectively. Since a pandiastolic reverse flow was detected in most
      patients in the control group over 60 years, it was not indicative of aortic
      regurgitation in these cases. However, an increased maximal diastolic velocity (>
      -37 cm/s) identified severe forms of aortic regurgitation in this age group with
      a sensitivity of 89% and a specificity of 100%. Therefore, severe forms of aortic
      regurgitation may be reliably identified by analysing the subclavian artery
      Doppler spectrum. In conclusion, the method is a useful adjunctive technique to
      other Doppler echocardiographic methods to assess the severity of aortic
      regurgitation.

PMID- 8269173
TI  - Improvement in the diagnosis of bioprosthetic valve dysfunction by
      transesophageal echocardiography.
AB  - Transthoracic two-dimensional echocardiography has been considered the method of
      choice for the non-invasive assessment of bioprosthetic valves. Recently,
      transesophageal echocardiography has provided a better imaging window for
      detecting valve abnormalities not identified otherwise, but pathologic
      confirmation is essential to establish the role of new diagnostic techniques in
      clinical practice. Therefore, the purpose of this study was to evaluate the
      usefulness of transesophageal echocardiography in determining the etiology of
      bioprosthetic valve dysfunction. Transthoracic and transesophageal two
      dimensional and color-flow Doppler echocardiography were performed on 44
      consecutive patients with suspected bioprosthetic dysfunction who underwent
      surgical intervention. At surgery a total of 63 abnormalities in 44 bioprostheses
      were identified: 31 (49.2%) flail cusps, 14 (22.2%) vegetations, four (6.3%)
      abscesses, four (6.3%) dehiscences, and 10 (15.9%) stenoses. Transesophageal
      echocardiography was superior to its transthoracic counterpart for the detection
      of flail cusps (96.7% vs. 54.8%, p < 0.01), vegetations (85.7% vs. 42.8%, p <
      0.01), abscesses (100% vs. 25.0%, p < 0.05), and dehiscences (100% vs. 25.0%, p <
      0.05). All patients with flail cusps had severe regurgitation as evaluated by
      color-flow Doppler. In bioprosthetic mitral stenosis, both methods provided
      accurate estimates of valve area, while in bioprosthetic aortic stenosis,
      transthoracic Doppler velocity measurements allowed calculation of valve area in
      four of six patients. In two patients with high flow velocities, the valve area
      was not estimated because of an inability to measure the left ventricular outflow
      tract dimension. Conversely, the transesophageal approach provided measurement of
      the outflow tract in all six patients, but Doppler velocities were not obtained
      in any of them.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269174
TI  - The zero pressure fixed medtronic intact porcine valve: an 8.5 year review.
AB  - The Medtronic Intact valve is the only porcine valve which is fixed in
      glutaraldehyde at zero pressure. This preserves near normal extensibility of the
      leaflet collagen, enabling full leaflet opening without kinking, which in turn
      should improve durability compared with low and high pressure fixed valves. From
      1983 to 1991, 265 patients had 276 Intact valves inserted (125 aortic, 129
      mitral, 22 tricuspid). The mean age was 53 years (10-81), with 24% below 40
      years. The 100% follow up represents 911 patient years and averaged 50 months (3
      106) in survivors. The actuarial survival was 54% +/- 9% at eight years, compared
      with a matched general population of 82%. The mean NYHA class was 3.2
      preoperatively and 1.2 at follow up. At eight years, freedom from infective
      endocarditis was 97% +/- 1%, from thromboembolism 89% +/- 3%, and from non
      structural dysfunction 96% +/- 2%. Reoperation was required in three patients for
      infective endocarditis, in six for non-structural dysfunction and in seven for
      structural valve deterioration (SVD). Freedom from SVD in the aortic position
      (mean age 59 years) was 100%, in the tricuspid position (mean age 48 years) 80%
      +/- 7%. In the mitral position, freedom from SVD was 86% +/- 10% in patients aged
      60 years or more (n = 39, two events), 96% +/- 4% in those aged 40-59 years (n =
      23, one event in a patient with renal failure), 67% +/- 16% in those aged 20-39
      years (n = 31, three events in two following pregnancy) and 38% +/- 28% in those
      under 20 years (n = 9, two events).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269175
TI  - In response to: Nygaard H, Thuesen L, Hasenkam JM, Pedersen EM. Assessing the
      severity of aortic valve stenosis by spectral analysis of cardiac murmurs
      (spectral vibrocardiography) Part I and Part II.

PMID- 8269176
TI  - Coping with motor neurone disease--an analysis using self-regulation theory.
AB  - Medicine and environmental changes have had tremendous success in controlling the
      infectious diseases that were the major causes of death in the last century.
      However, the consequential extension of life has been accompanied by an increase
      in the number of persons living with and dying of chronic illness. Despite these
      changes and their implications, the means by which people cope with such
      illnesses has only recently begun to receive the attention the subject warrants.
      Such diseases have a high prevalence in the population and self-detection and
      self-management are critical to the treatment and control of chronic disease and
      disability. This paper examines how people cope with motor neurone disease and
      sets this in the context of earlier research on psychological aspects of chronic
      disease and current theoretical approaches to coping with long-term ill health.

PMID- 8269177
TI  - Bereavement--whose responsibility?
AB  - Bereavement care begins during the terminal phase of motor neurone disease as the
      family prepare for the death. Due to the long-term nature of the illness there is
      a need to allow the expression of painful feelings and to ensure that the family
      is adequately supported. The responsibility for care in bereavement lies not only
      with the family but with the health care professions, bereavement support groups
      and the whole community.

PMID- 8269178
TI  - Recent advances in atomic force microscopy of DNA.
AB  - Three advances involving DNA in atomic force microscopy (AFM) are reported here.
      First a HEPES-Mg buffer has been used that improves the spreading of DNA and
      provides good DNA coverage with as little as 200-500 picograms per sample.
      Second, the new "tapping" mode has been used to improve the ease and resolution
      of AFM-imaging of DNA in air. Finally, AFM images are presented of single
      stranded phi X-174 virion DNA with the gene 32 single-stranded binding protein. A
      summary of the current state of the field and of the methods for preparing and
      imaging DNA in the AFM is also presented.

PMID- 8269180
TI  - Bibliography of the current world literature.

PMID- 8269179
TI  - Augmented coronary blood flow response to intracoronary norepinephrine after
      ventricular sympathectomy.
AB  - BACKGROUND: Ventricular sympathetic denervation may occur as a result of
      myocardial infarction or heart transplantation. The present study examined the
      time-dependent effects of surgical ventricular sympathectomy on coronary flow and
      myocardial contractile responses to intracoronary norepinephrine administration
      in conscious dogs. METHODS: Adult mongrel dogs (18-26 kg), were either
      ventricular sympathectomized or served as a sham-operated control. Animals were
      studied 2, 4, and 8 weeks after surgery. Measurements of left ventricular
      systolic pressure (LVSP), maximum rate of left ventricular pressure generation
      (dP/dtmax), maximum negative rate of segmental shortening (-dL/dtmax), heart
      rate, and mean circumflex flow velocity (CFV) were obtained before and after
      bolus administration of norepinephrine into the circumflex artery in doses
      ranging from 0.01 to 0.50 microgram. RESULTS: Intracoronary norepinephrine
      administration caused significant increases in LVSP, dP/dtmax, -dL/dtmax, heart
      rate, and CFV. After reaching a peak or maximum response, these variables
      returned to their respective preinjection values, except for CFV, which exhibited
      a biphasic response. CFV continued to decline below control levels, indicating a
      vasoconstrictor response to norepinephrine, before returning back to preinjection
      levels. With the 0.5-microgram dose of intracoronary norepinephrine, the percent
      increases in CFV were 124% +/- 25% and 105% +/- 15% (P < 0.05) at 2 and 4 weeks
      respectively, compared with the sham-operated controls, which only increased 56%
      +/- 15%. The response to the 0.5-microgram dose of norepinephrine at 8 weeks (61%
      +/- 6%) was not significantly different from control. Elevated myocardial
      contractile responses in the sympathectomized hearts were also evident at 2 and 4
      weeks, but not at 8 weeks. The vasoconstrictor response to norepinephrine
      administration was not significantly different between sympathectomized and sham
      operated hearts. Finally, there was no difference in the change in LVSP,
      dP/dtmax, or heart rate between any of the groups at any of the doses.
      CONCLUSIONS: These results suggest that a supersensitivity to the coronary
      functional hyperemic response after intracoronary norepinephrine is present in
      ventricular sympathectomized hearts, but a coronary constrictor supersensitivity
      does not exist.

PMID- 8269181
TI  - The current role of digoxin in the treatment of heart failure.

PMID- 8269182
TI  - The use of angiotensin-converting enzyme inhibitors in the treatment and
      prevention of congestive heart failure.

PMID- 8269183
TI  - Fish oil decreases serum homocysteine in hyperlipemic men.
AB  - BACKGROUND: Because of the inverse relation between dietary fish consumption and
      coronary heart disease and because of the importance of serum homocysteine as an
      independent risk factor for atherosclerosis, the effect of fish oil on serum
      homocysteine was studied in hyperlipemic men. METHODS: Fifteen men with either
      type IIa or IIb lipoproteinemia or hypertriglyceridemia were maintained on a
      controlled, balanced diet and given either fish oil or olive oil supplements, 12
      g/d for 3 weeks, followed by a cross-over period of 3 weeks during which the
      olive oil or fish oil supplements were given in reverse order. Serum homocysteine
      was determined by liquid chromatography of acid hydrolyzates of whole serum.
      RESULTS: Fish oil was found to diminish serum homocysteine levels in 14 of 17
      subjects (P < 0.01). Serum homocysteine was 48% +/- 33% less than control values
      in seven of nine patients and 36% +/- 22% less than values in seven of eight
      subjects who had first received olive oil. There was no effect of olive oil
      supplements on serum homocysteine, compared with control values, but olive oil
      produced an increase in serum homocysteine in those who had first received fish
      oil. Serum triglycerides and very low-density lipoprotein were decreased by fish
      oil in patients who were first given olive oil, in agreement with previous
      studies. There was no effect of either fish oil or olive oil on total
      cholesterol, apolipoprotein B, low-density lipoprotein, or high-density
      lipoprotein. CONCLUSIONS: The protection against coronary heart disease afforded
      by a diet rich in fish may be attributed to the lowering of serum homocysteine
      levels by the n-3 polyunsaturated fatty acids of fish oils.

PMID- 8269184
TI  - Slow coronary flow complicating elective balloon angioplasty in postthrombolytic
      patients.
AB  - BACKGROUND: Coronary blood flow after percutaneous transluminal coronary
      angioplasty (PTCA), as judged by the clearance of contrast media from the
      arterial bed, is usually brisk. Reduced coronary blood flow after PTCA in the
      absence of arterial dissection, air embolism, and large vessel spasm is unusual
      and the mechanism that causes it is incompletely understood. METHODS: All cases
      of reduced coronary blood flow after PTCA during a 12-month period were
      identified from a prospective database. Clinical, procedural, and angiographic
      findings were reviewed. RESULTS: Four patients demonstrated reduced coronary flow
      after PTCA in the absence of intimal dissection, air embolism, or large vessel
      spasm. All of the patients had been treated several days earlier with
      thrombolytic agents for acute myocardial infarction. The reduced coronary flow
      developed despite pretreatment with aspirin, heparin, and vasodilators. Symptoms
      of myocardial ischemia developed in each patient, including myocardial necrosis
      in three patients, complete heart block in one, and delayed cardiac rupture in
      one. This syndrome was not rapidly reversed with intracoronary nitroglycerin and
      thrombolytic agents. CONCLUSIONS: Percutaneous transluminal coronary angioplasty
      of recently lysed or freshly thrombotic coronary arteries may predispose to the
      activation of potent vasoconstrictors or distal embolization of microparticulate
      atherothrombotic debris, leading to slow coronary flow and myocardial ischemia.

PMID- 8269185
TI  - Evidence for a systemic defect of resistance-sized arterioles in hypertrophic
      cardiomyopathy.
AB  - BACKGROUND: To investigate whether the abnormalities of coronary arterioles
      observed in association with hypertrophic cardiomyopathy represent a generalized
      phenomenon, both forearm and coronary vasodilator reserve were measured in 12
      patients with hypertrophic cardiomyopathy. METHODS: Forearm vasodilator reserve
      was evaluated by measuring minimal forearm vascular resistance (Rmin, the ratio
      of mean intra-arterial pressure to peak forearm blood flow measured by venous
      plethysmography) under conditions of maximal postocclusive reactive hyperemia.
      RESULTS: In a subgroup (n = 5) of patients, the intra-arterial infusion of sodium
      nitroprusside combined with arterial occlusion did not produce additional
      vasodilation, indicating that the ischemic stimulus was indeed maximal. Coronary
      reserve was quantitated by measuring left ventricular blood flow (13N-ammonia and
      positron emission tomography) and coronary resistance at baseline and after
      intravenous dipyridamole (0.56 mg/kg). Rmin was significantly greater in patients
      than in a group of age- and sex-matched controls. The percentage change in
      coronary resistance after dipyridamole was significantly related to Rmin, whereas
      no correlation was found between change in coronary resistance and individual
      septal thickness values. CONCLUSIONS: Independent of cardiac hypertrophy,
      systemic and coronary arterioles of patients with hypertrophic cardiomyopathy are
      affected by an abnormality that may contribute to the clinical evolution of this
      syndrome.

PMID- 8269186
TI  - Angiographic restenosis after angioplasty: comparison of definitions and
      correlation with clinical outcome.
AB  - BACKGROUND: The aim of this study was to assess which of the currently used
      definitions of restenosis most closely indicates degree of recurrence and
      clinical status by 1) correlating percentage luminal renarrowing with restenosis
      defined according to each of four definitions, and 2) evaluating which definition
      was best predicted by clinical recurrence. METHODS: Quantitative angiography in
      125 patients was undertaken either at time of early clinical presentation or at 6
      month follow-up after percutaneous transluminal coronary angioplasty (PTCA).
      Absolute luminal diameters measured before and after PTCA and at follow-up were
      plotted as the percentage return from post-PTCA toward pre-PTCA value. All
      patients were also defined as restenosed or not restenosed according to each of
      the four definitions. RESULTS: The angiographic restenosis rate varied from 31%
      to 47%. Other than for "loss of 50% absolute gain," all definitions defined
      restenosis in some patients, despite the degree of return from post-PTCA to pre
      PTCA value being less than 50%. Early recurrent symptoms predicted angiographic
      restenosis best, irrespective of angiographic definition, whereas history of
      recurrent angina or positive exercise testing alone at follow-up were poor
      predictors (range, 0.46 to 0.54). The predictive value increased (0.75 to 0.87)
      when exercise testing was positive in patients complaining of angina. The
      definition "loss of 2 standard deviations" gave the lowest values for positive or
      negative predictive values irrespective of clinical parameter. CONCLUSIONS: "Loss
      of 50% absolute gain" may be the best compromise definition. Patients admitted
      early with angina should undergo recatheterization, whereas exercise tests should
      be reserved for patients who complain of angina at routine follow-up.

PMID- 8269187
TI  - Reversible left ventricular dysfunction with coronary stenotic or obstructive
      lesions in Kawasaki disease.
AB  - BACKGROUND: Few studies have been reported on the prognosis or reversibility of
      ischemic myocardial lesions in Kawasaki disease. In this study, the
      pathophysiologic causes of reversible left ventricular dysfunction were evaluated
      in seven children with severe stenotic coronary lesions caused by Kawasaki
      disease. METHODS: The clinical process and the changes of coronary lesions in the
      repeated angiography were retrospectively evaluated in seven children. The ages
      of the seven patients (six boys and one girl) ranged from 7 to 15 years (mean,
      10.4 +/- 2.6 y); the duration from the onset of Kawasaki disease to the last
      angiographic study ranged from 6 to 15 years (mean, 9.6 +/- 3.0 y). RESULTS:
      During the acute stage, an acute myocardial infarction was detected clinically in
      two patients, transient ST depression in two, and deep Q waves without any
      symptoms in the remaining three patients. In the first angiographic study (2 mo
      to 6 y after the onset of Kawasaki disease), significant left ventricular
      dysfunction was observed in the posterior or inferior wall in all patients. In
      the right coronary arteries, giant aneurysms (> or = 8 mm in diameter) were
      angiographically detected in two patients, localized stenosis (> or = 95%) in
      one, and recanalization in four. In a recent angiographic study, the left
      ventricular dysfunction had normalized in all seven patients. Recanalization was
      observed, even in two patients with giant aneurysms and in one with localized
      stenosis. Collateral circulation was detected in five patients in this study.
      Abnormal deep Q waves on ECG were detected in only one patient, and no abnormal
      findings on ECG were seen in the remaining six. Upon 201TI myocardial
      scintigraphy, no reduction of 201TI uptake was observed in any of the seven
      patients at the site of the abnormal wall motion on the first angiography.
      CONCLUSIONS: The regional left ventricular dysfunction in the seven patients may
      have been induced by severe acute ischemia due to a transient right coronary
      obstruction or by severe chronic ischemia due to coronary lesions. Eventually,
      left ventricular wall motion normalized after an improvement in the blood flow
      supply as a result of early recanalization and development of collateral
      circulation.

PMID- 8269188
TI  - Changes in QRS segments during exercise in relation to scintigraphic myocardial
      perfusion defects: a multivariate analysis.
AB  - BACKGROUND: The relation between QRS changes during exercise and ischemic heart
      disease is controversial. The present investigation addressed whether exercise
      QRS changes are related 1) to myocardial ischemia or necrosis, 2) to possibly
      confounding factors such as baseline QRS size and changes in heart rate and ST
      magnitude during exercise, and 3) to the location of scintigraphic defects.
      METHODS: Advanced computerized vectorcardiography (MIDA1000, Ortivus Medical AB,
      Sweden) was recorded in 71 consecutive patients referred for 201TI exercise
      myocardial scintigraphy. Maximal exercise tests were performed in the sitting
      position on a bicycle ergometer. Planar scintigraphic images were obtained
      immediately after exercise and 4 hours later in three projections, and were
      evaluated blindly. RESULTS: Exercise QRS changes correlated to baseline QRS size
      (X, Y, and Z leads; P < 0.005), change in heart rate (X and Y leads; P < 0.01),
      and ST change at J + 20 ms (X, Y, and Z leads; P < 0.0001). Increased QRS
      magnitudes in the Y and Z leads correlated to late perfusion defects (P <
      0.0001). These correlations remained after correction for baseline QRS size and
      changes in heart rate and ST magnitude at J+20 ms during exercise (P < 0.0001).
      No consistent relationships were observed between the location of myocardial
      perfusion defects and the stress-induced alterations in QRS. CONCLUSIONS:
      Baseline QRS size and changes in heart rate and ST magnitude may have important
      confounding effects on the QRS response to exercise. However, even after
      consideration of these factors, the QRS response to exercise was related to late
      (4 h) scintigraphic myocardial perfusion defects. The findings suggest that the
      presence of myocardial infarctions or long-lasting ischemia after exercise is
      associated with increased QRS magnitudes during exercise.

PMID- 8269189
TI  - 'Naturally occurring' low blood cholesterol and excess mortality.

PMID- 8269190
TI  - Causes of hypocholesterolemia.

PMID- 8269191
TI  - Blood cholesterol and non-coronary mortality.

PMID- 8269192
TI  - Serum cholesterol levels and atherosclerosis.

PMID- 8269193
TI  - Diet, blood cholesterol levels, and coronary heart disease.

PMID- 8269194
TI  - Clinical and histological determinants of smooth-muscle cell outgrowth in
      cultured atherectomy specimens: importance of thrombus organization.
AB  - BACKGROUND: Coronary atherectomy provides a unique opportunity to obtain plaque
      tissue from a wide variety of clinical syndromes. We investigated the relation
      between the clinical status and histopathological substrate of tissue retrieved
      during directional coronary atherectomy and the proliferative and migratory
      potential of smooth-muscle cells judged from successful outgrowth during cell
      culture. METHODS: After directional coronary atherectomy, tissue samples were
      examined macroscopically, divided into two equal pieces, and separately subjected
      to cell culture and histopathological study. Cell culture was performed using an
      explant technique. In-vitro smooth-muscle cell outgrowth was related to clinical
      and histological variables. RESULTS: Atherosclerotic tissue was obtained from 98
      consecutive atherectomy procedures. Histological examination revealed a broad
      spectrum of appearances, ranging from complex atheroma containing dense fibrous
      tissue, calcium deposits, macrophages, and necrotic debris to neointimal
      proliferation and organized thrombi. Smooth-muscle cell outgrowth was observed in
      43 of the 98 samples (44%). Although not affected by any of the clinical
      variables, cell outgrowth was influenced by histological variables, in particular
      the presence of organizing thrombi. Outgrowth was successful in eight out of 10
      samples with thrombus (80%) and in only 35 out of 88 (40%) without (P = 0.03).
      CONCLUSION: The presence of organizing thrombi in the retrieved tissue
      facilitates smooth-muscle cell outgrowth and suggests an enhanced proliferative
      and migratory potential. These findings may be relevant to the understanding of
      neointimal proliferation in coronary syndromes where mural thrombosis is likely
      to occur.

PMID- 8269195
TI  - The role of endothelium-derived nitric oxide in acetylcholine-induced coronary
      vasoconstriction in closed-chest pigs.
AB  - BACKGROUND: The effects of an inhibitor of endothelium-derived nitric oxide on
      acetylcholine (ACh)-induced coronary vasoconstriction were examined in 13
      anesthetized closed-chest pigs. METHODS: Coronary blood flow was measured using a
      previously implanted ultrasonic transmit-time flow probe. The diameter of the
      large epicardial coronary arteries was assessed by coronary arteriography.
      RESULTS: Intracoronary infusions of ACh (0.1, 0.3, and 1.0 micrograms/kg/min)
      resulted in dose-dependent decreases in coronary blood flow. Arterial pressure
      and heart rate were minimally altered by ACh. The high dose of ACh decreased
      coronary blood flow by 67 +/- 11% and caused myocardial ischemia, demonstrated by
      ST-segment elevation. Coronary arteriograms revealed diffuse narrowing of
      peripheral coronary arteries and a filling delay of the contrast medium evoked
      with ACh. Vasospasm of the large epicardial coronary arteries was not observed.
      The decreases in coronary blood flow with ACh were inhibited by atropine (0.2
      mg). Intracoronary administration of an inhibitor of endothelium-derived nitric
      oxide, NW-nitro-L-arginine (NNLA, 1.0 mg/kg), slightly increased arterial
      pressure but did not change baseline coronary blood flow. The percentage
      decreases in coronary blood flow induced by ACh were significantly augmented by
      NNLA administration, but those induced by prostaglandin F2 alpha (0.5
      microgram/kg/min) were not affected by NNLA. The response of the large coronary
      arteries to ACh was not altered by NNLA. CONCLUSIONS: Our results suggest that,
      in pigs, ACh decreased coronary blood flow and caused myocardial ischemia as a
      result of the direct cholinergic vasoconstriction of peripheral small coronary
      arteries. The augmentation of ACh-induced coronary vasoconstriction by NNLA
      suggests that ACh facilitated the release of endothelium-derived nitric oxide,
      which attenuated the direct coronary vasoconstriction induced by ACh.

PMID- 8269196
TI  - Enhanced excretion of urinary leukotriene E4 in coronary artery disease and after
      coronary artery bypass surgery.
AB  - BACKGROUND: Excretion of leukotriene (LT) E4, the major urinary metabolite of
      cysteinyl leukotrienes in humans, is increased in patients with unstable angina
      and myocardial infarction, suggesting that cysteinyl leukotrienes are released
      into the circulation during episodes of myocardial ischaemia. Furthermore,
      leukotrienes are known to induce potent vasoconstrictive effects in human
      atherosclerotic coronary arteries and the saphenous vein. Accordingly, we
      measured urinary excretion of LTE4 in patients with stable coronary artery
      disease both before and after coronary artery bypass surgery, and in age-matched
      healthy controls, to study the relation between the systemic synthesis of
      cysteinyl leukotrienes and stable coronary artery disease, as well as the
      possible changes after bypass surgery. METHODS: LTE4 was isolated from urine
      samples by solid-phase extraction, purified by reverse-phase high-performance
      liquid chromatography, and subsequently quantified by radioimmunoassay. RESULTS:
      In patients with coronary artery disease, preoperative urinary LTE4 levels were
      normally distributed on a log10 scale, with a genometric mean of 115 pmol/mmol
      creatinine (95% confidence interval 67-196) compared with 63.0 pmol/mmol
      creatinine (95% confidence interval 47.9-82.7) in healthy subjects (P < 0.05).
      Urinary LTE4 levels increased further in patients after coronary artery bypass
      surgery with levels peaking on the second day after surgery (266.2 pmol/mmol
      creatinine, 95% confidence interval 167.2-423.9) at significantly higher than
      preoperative levels (P < 0.02), and then decreasing by day 3. CONCLUSIONS: Levels
      of cysteinyl leukotrienes are raised in coronary artery disease patients both
      before and after coronary artery bypass surgery. As these mediators are capable
      of inducing potent vasoconstrictive effects on atherosclerotic coronary arteries
      and the saphenous vein, our results could have important clinical and possibly
      therapeutic implications.

PMID- 8269198
TI  - Transthoracic and transesophageal echocardiography to diagnose ventricular septal
      rupture: importance of right heart infarction.
AB  - BACKGROUND: Rapid and accurate diagnosis of ventricular septal rupture (VSR)
      remains difficult, and the monitoring of hemodynamic deterioration is a
      prerequisite for the institution of adequate therapy. The timing of surgical
      repair is a matter of controversy. METHODS: Transthoracic, transesophageal, color
      Doppler, and contrast echocardiography were evaluated in 17 patients with VSR in
      whom the diagnosis was confirmed by catheterization, surgery, or necropsy.
      RESULTS: Routine transthoracic echocardiography visualized VSR in four out of 17
      patients and, with additional views, in 12 out of 17 patients. Color Doppler
      echocardiography identified the rupture in 15 out of 16, and contrast
      echocardiography in 11 out of 11 patients. VSR was identified using
      transesophageal echocardiography in six out of nine patients, and using color
      Doppler and contrast echocardiography in all patients. Eight out of 10 patients
      who developed right heart myocardial infarction (RMI) died, whereas all patients
      without RMI survived (P = 0.0070). Similarly, eight out of 10 patients with shock
      died, whereas all patients without survived (P = 0.0070). Shock occurred more
      often in patients with RMI (eight out of 10) than in patients without (two out of
      six). All patients with both RMI and shock died, whereas those without both
      conditions survived (P = 0.0002). CONCLUSION: Modern echocardiography is the
      method of choice in the diagnosis of VSR. Right ventricular function should be
      evaluated in patients with VSR because patients with RMI are at high risk of
      hemodynamic deterioration, with poor outcome. RMI, visible as abnormal wall
      motion, was identified better with transesophageal than with transthoracic
      echocardiography.

PMID- 8269197
TI  - Free radicals, antioxidants, and endothelial cell damage after percutaneous
      transluminal coronary angioplasty.
AB  - BACKGROUND: Oxygen-derived free radicals (ODFRs) and subsequent lipid
      peroxidation may be responsible for myocardial damage associated with
      ischaemia/reperfusion after percutaneous transluminal coronary angioplasty
      (PTCA). These potentially cytotoxic ODFRs are likely to be generated in the
      plasma, where the primary target organ or cell may be the endothelium. Some of
      these toxic effects may be limited by the action of antioxidant enzymes such as
      glutathione peroxidase (GPx). The aim of this study was to determine whether
      there was evidence of ODFR-mediated damage to the endothelium after PTCA and to
      examine the roles of lipid peroxides and GPx. METHODS: Serial samples of plasma
      were obtained at the time of catheter insertion, at the time of balloon
      inflation, 10 min after inflation, and 60 min after inflation, from 16 patients
      undergoing PTCA. We measured levels of von Willebrand factor (vWf, a specific
      product of the endothelium and a marker of damage), thiobarbituric acid reactive
      substances (TBARS, an indirect measure of the activity of ODFRs in peroxidizing
      lipoproteins), and the antioxidant GPx. RESULTS: There was a simultaneous peak in
      the levels of TBARS (P = 0.0096) with a fall in the levels of GPx (P = 0.004) 10
      min after balloon deflation. Sixty min after balloon deflation, GPx levels were
      still reduced (P = 0.005) but there was a rise in levels of vWf (P = 0.038).
      CONCLUSIONS: Our interpretation of these data is that an early peak in ODFR
      activity associated with PTCA causes an endothelial injury 1 h after inflation.
      This may be related to the reduced ability of GPx to scavenge ODFRs.

PMID- 8269199
TI  - Diagnostic value of left ventricular dyssynergy patterns in ischemic and non
      ischemic cardiomyopathy.
AB  - BACKGROUND: The distinction between ischemic and non-ischemic cardiomyopathy has
      important clinical implications. The objective of the present study was to
      investigate whether left ventricular dyssynergy patterns, detected by
      quantitative analysis of ultrasound images, differed in these two pathological
      processes. METHODS: Fifty-six consecutive patients with congestive heart failure
      (New York Heart Association functional class II-IV) secondary to depressed left
      ventricular systolic function (ejection fraction < or = 35% during diagnostic
      cardiac catheterization) were studied. Twenty patients were eliminated from
      further analysis because they met one or more exclusion criteria. The remaining
      36 were divided into two groups based on the presence (ischemic cardiomyopathy)
      or absence (non-ischemic cardiomyopathy) of a > or = 50% narrowing of the luminal
      diameter in one or more coronary arteries. In all patients, a standard two
      dimensional echocardiographic study was obtained. Apical four- and two-chamber
      views with optimal endocardial and epicardial resolution were selected for
      analysis, and the left ventricular contour was divided into six segments of
      interest. Optimal endocardial and epicardial resolution were defined according to
      an original internal quality score system. For each of the six segments of
      interest, regional ejection fraction and regional segmental thickening were
      estimated. Data analysis was then performed on the average values of regional
      ejection fraction and regional segmental thickening obtained across the entire
      left ventricular contour. In each patient, regional ejection fraction range and
      regional segmental thickening range were calculated by subtracting the minimum
      from the maximum value of regional ejection fraction and regional segmental
      thickening obtained across a left ventricular contour. RESULTS: Regional ejection
      fraction and regional segmental thickening did not differ significantly between
      the two groups. However, regional ejection fraction range and regional segmental
      thickening range were significantly greater in patients with ischemic
      cardiomyopathy than in patients with non-ischemic cardiomyopathy [28.32 +/- 11.17
      versus 14.74 +/- 7.73% (P < 0.001) and 47.80 +/- 16.00 versus 24.64 +/- 9.39% (P
      < 0.001), respectively]. Overlap of findings was observed in 20% of the values
      for regional ejection fraction range but in only 14% of those for regional
      segmental thickening range. CONCLUSIONS: Patients with ischemic cardiomyopathy
      demonstrate a non-uniform dyssynergy that can be differentiated from a more
      uniform hypokinesis observed in those with non-ischemic cardiomyopathy.
      Computerized ultrasonic image analysis can distinguish characteristic dyssynergic
      patterns in patients with cardiomyopathy. Measurements of segmental wall
      thickening provide a more accurate assessment of regional function.

PMID- 8269200
TI  - Coronary thrombolysis with K1K2Pu, a chimeric tissue-type and urokinase-type
      plasminogen activator: a feasibility study in six patients with acute myocardial
      infarction.
AB  - BACKGROUND: K1K2Pu is a recombinant chimeric tissue-type and urokinase-type
      plasminogen activator consisting of the two kringle domains (K1 and K2) of human
      tissue-type plasminogen activator (t-PA) and the serine proteinase domain (Pu) of
      single-chain urokinase-type plasminogen activator (scu-PA). In experimental
      animal models of thrombosis, its thrombolytic potency has been shown to be five-
      to 10-fold greater than that of its parent molecules. METHODS: The effect of a
      bolus injection of K1K2Pu on coronary thrombolysis over 30 min was evaluated in
      six patients with acute myocardial infarction of less than 5 h duration in whom
      total occlusion of the infarct-related artery was confirmed using angiography.
      RESULTS: In two patients given an intravenous bolus of 10 mg over 5 min,
      persistent coronary artery recanalization was not observed within 30 min. In two
      out of four patients given a second bolus of 10 mg K1K2Pu, 15 min after the
      first, persistent coronary recanalization occurred within 30 min. The four
      patients without recanalization within 30 min were immediately given 100 mg t-PA
      over 90 min. In all patients the infarct-related artery was patent after 24 h,
      and the hospital course was uneventful. The bolus injections did not produce
      significant fibrinogen breakdown or alpha 2-antiplasmin consumption within 30
      min. The plasma K1K2Pu level increased to 2-3 micrograms/ml after the first bolus
      injection and to 4-5 micrograms/ml after the second. K1K2Pu disappeared from the
      plasma with an initial half-life of 9 min and a clearance of approximately 50
      ml/min. CONCLUSION: A bolus injection of 20 mg K1K2Pu is well tolerated and can
      induce clot-selective coronary thrombolysis in patients with acute myocardial
      infarction.

PMID- 8269201
TI  - The in-vitro effect of antineoplastic agents on proliferative activity and
      cytoskeletal components of plaque-derived smooth-muscle cells from human coronary
      arteries.
AB  - BACKGROUND: Restenosis after successful percutaneous transluminal coronary
      angioplasty remains the major clinical problem limiting the long-term efficacy of
      the treatment. Recent advances in the understanding of the biology of restenosis
      indicate that its cause is predominantly a multifactorial stimulation of smooth
      muscle cell proliferation. The aim of this study was to investigate the in-vitro
      effect of antineoplastic agents on smooth-muscle cells isolated from human
      coronary plaque material. METHODS: Atherosclerotic tissue from coronary arteries
      was extracted from 15 patients of both sexes by thrombendarterectomy. Cells were
      isolated using enzymatic disaggregation and identified to be smooth-muscle cells
      with fluorescent antibodies for smooth-muscle-specific alpha-actin. The
      antineoplastic agents cytarabine (500-0.005 micrograms/ml), doxorubicin (50
      0.0005 micrograms/ml), and vincristine (10-0.0001 micrograms/ml) were added to
      the cultures. Six days after seeding, the cells were trypsinized and then
      counted. RESULTS: All three antineoplastic agents had a strong dose-dependent
      antiproliferative effect on cultured smooth-muscle cells. After the application
      of cytostatic agents, cells either became rounded or underwent complete lysis.
      Cytoskeletal elements, such as actin, microtubules, and vimentin, were largely
      altered. CONCLUSION: This investigation examined the potential role of
      antineoplastic therapy in the prevention of restenosis after coronary
      angioplasty. The development of new intravascular delivery systems, such as
      coated stents, may open the way for local antiproliferative strategies in
      interventional cardiology.

PMID- 8269202
TI  - The role of balloon aortic valvuloplasty in current practice.

PMID- 8269203
TI  - Bibliography of the current world literature.

PMID- 8269204
TI  - Premature atherosclerosis and familial hypercholesterolemia.

PMID- 8269205
TI  - Anomalous coronary arteries and coronary artery fistulas in infants and children.

PMID- 8269206
TI  - Coronary artery anatomy and transposition of the great arteries.

PMID- 8269207
TI  - Early reocclusion after successful thrombolysis is related to lesion length and
      roughness.
AB  - BACKGROUND: Reocclusion is a significant problem after thrombolysis. Results of
      previous studies conflict regarding the association of various features of
      postlytic lesions that might predict reocclusion. METHODS: A computer-assisted
      algorithm was therefore used to quantitatively measure edge roughness in the 90
      minute postlysis angiogram of 84 patients receiving recombinant tissue
      plasminogen activator within 6 hours of chest pain. RESULTS: Twenty-five patients
      had reocclusion, and 59 did not. The baseline angiogram showed no differences
      between these two groups with respect to minimal dimensions or relative
      percentage of stenosis. Length was greater in the reocclusion group (12.2 +/- 5.0
      vs 10.0 +/- 4.2 mm, P < 0.05). Three of four roughness indices based on curvature
      analysis indicated greater roughness in those patients with reocclusion. These
      differences were largely due to the increased length of these lesions. The scaled
      edge-length ratio, an index of roughness that is independent of length, was,
      however, significantly greater in the reocclusion group (1.15 +/- 0.10 vs 1.09 +/
      0.08, P < 0.006). Multiple regression analysis showed that lesion length, the
      scaled edge-length ratio, and the number of features (invaginations and
      evaginations) per cm correlated independently with the risk for reocclusion.
      CONCLUSIONS: The length and roughness of postlytic residual lesions are
      determinants of reocclusion.

PMID- 8269208
TI  - Safety and antiplatelet effect of murine monoclonal antibody 7E3 Fab directed
      against platelet glycoprotein IIb/IIIa in patients undergoing elective coronary
      angioplasty.
AB  - BACKGROUND: Excessive platelet deposition at the site of arterial damage due to
      coronary angioplasty plays an important role in the pathophysiology of both
      abrupt closure and restenosis after that procedure. Even aspirin, a relatively
      weak platelet antagonist, decreases the complications of coronary angioplasty.
      This study was designed to provide preliminary safety and efficacy data on the
      use of a much more powerful antiplatelet agent, m7E3 Fab, a prototype murine
      monoclonal antibody fragment that binds directly to the platelet glycoprotein
      IIb/IIIa receptor mediating aggregation in patients undergoing coronary
      angioplasty. METHODS: Twenty-three patients referred for elective coronary
      angioplasty who met prespecified criteria designed to minimize risk of bleeding
      received, in groups of four to six patients, escalating bolus doses of 0.15 to
      0.35 mg/kg of this agent immediately before coronary angioplasty. Heparin was
      administered in the usual manner, but aspirin was withheld for 24 hours before
      coronary angioplasty and until bleeding times and platelet aggregation had
      returned to normal after angioplasty. Glycoprotein IIb/IIIa binding site
      occupation, platelet aggregation response to 20 microM of adenosine diphosphate,
      and data on bleeding times were acquired at baseline and at 2, 6, 24, 48 and 72
      hours after m7E3 Fab administration. Clinical safety and efficacy were also
      monitored throughout the time of hospitalization, and delayed antimurine immune
      responses were assayed. Five similar patients received aspirin (325 mg orally per
      day) but otherwise received the same treatment, thus serving as controls.
      RESULTS: Treatment with m7E3 Fab resulted in a dose-dependent occupation of
      binding sites to a maximum of 93% at 2 hours in the highest-dose groups, with an
      associated graded inhibition of platelet aggregation and increase in bleeding
      time significantly exceeding that seen in control patients, with a gradual
      recovery over 6 to 48 hours. Percutaneous transluminal coronary angioplasty was
      successfully performed in 18 of 21 patients (86%) in whom it was attempted.
      Arterial and venous sheath removal 24 hours after m7E3 Fab dosing was largely
      uneventful. No thrombotic complications were seen, and only one patient
      (excluding a patient who underwent uneventful urgent bypass surgery) had bleeding
      severe enough to require packed red cell transfusion. Eight patients (36%)
      developed late antibody titers against m7E3 Fab. CONCLUSIONS: This murine
      monoclonal antibody provides potent antiaggregatory action and thus may be useful
      in preventing thrombotic complications of coronary angioplasty, but studies of
      its safety and efficacy during longer infusions and with larger numbers of
      patients are needed. Less immunogenic forms of the antibody may be more
      clinically useful.

PMID- 8269209
TI  - Coronary artery spasm is a major cause of sudden cardiac arrest in survivors
      without underlying heart disease.
AB  - BACKGROUND: The role of coronary spasm in underlying disease-free patients who
      were resuscitated from sudden cardiac arrest remained uncertain. This study
      investigated the cause of cardiac arrest, and the etiologic and prognostic
      differences were compared between patients with underlying heart disease (group
      I) and those patients without underlying heart disease (group II). METHODS:
      Twenty-five survivors of sudden cardiac arrest were classified into two groups
      according to the presence or absence of underlying heart disease. To investigate
      the cause of cardiac arrest, we performed ergonovine testing and
      electrophysiologic study. Fifteen of the patients had underlying heart disease,
      while 10 did not. RESULTS: Electrophysiologic abnormalities were found in 13 of
      the 15 patients in group I. In group II, spontaneous attack of coronary spasm
      occurred in four patients during the observation period, and coronary spasm was
      induced in three of the remaining six period of 32 +/- 23 months, whereas no
      patients in group II had recurrence of sudden cardiac arrest at a median follow
      up of 32 months (range, 10 to 72 months). CONCLUSIONS: Electrophysiologic study
      identified a potential cause in 13 of 15 patients with underlying heart disease.
      Coronary spasm was involved in the pathogenesis of sudden cardiac arrest in
      survivors without identifiable underlying heart disease.

PMID- 8269210
TI  - Variation in plasma platelet-activating factor degradation and serum lipids after
      acute myocardial infarction.
AB  - BACKGROUND: Platelet-activating factor is a biologically potent phospholipid that
      may mediate cell damage in patients with myocardial ischemia. In plasma, its
      inactivation to lyso-platelet-activating factor is catalyzed by a specific,
      lipoprotein-associated acetylhydrolase. Because lipoprotein levels decrease after
      myocardial infarction, a possible reduction was suspected to occur in plasma
      degradation of platelet-activating factor. METHODS: Degradation of platelet
      activating factor was examined in an optimized assay of acetylhydrolase activity
      and in relation to the in vitro plasma half-life of platelet-activating factor.
      These, plasma lyso-platelet-activating factor and serum lipids, were measured in
      12 men with acute myocardial infarction at presentation and at 2 and 7 days
      later. RESULTS: Acetylhydrolase activity was depressed at day 2 and at day 7. The
      corresponding increase in plasma half-life of platelet-activating factor was
      minimal and insignificant. A significant linear relation existed between the half
      life of platelet-activating factor and the reciprocal of acetylhydrolase activity
      at each time of study, indicating a hyperbolic relation between the two. By day
      2, total and low-density lipoprotein cholesterol had decreased but showed no
      further change by day 7; high-density lipoprotein cholesterol had not decreased
      at day 2 but was depressed by day 7. Plasma lyso-platelet-activating factor had
      decreased by day 2 and had returned to its initial level by day 7. CONCLUSIONS:
      Acute myocardial infarction is associated with depression of plasma
      acetylhydrolase activity, and because of the hyperbolic relation between the
      plasma enzyme activity and the half-life of platelet-activating factor, the
      latter shows negligible change. Hence, the mechanism for the inactivation of any
      platelet-activating factor that might be released as a consequence of tissue
      damage is preserved.

PMID- 8269211
TI  - The long-term predictive value of an exercise thallium-201 scintigraphy for
      patients with acute chest pain but without myocardial infarction.
AB  - BACKGROUND: Patients who are hospitalized because of chest pain and suspected
      acute myocardial infarction, but in whom the diagnosis is ruled out, are at high
      risk for subsequent cardiac events (cardiac death or nonfatal acute myocardial
      infarction). Risk stratification was done for 158 such patients who underwent
      exercise thallium-201 scintigraphy at the time of discharge. METHODS: Thirty
      eight patients (24%) were women, and all patients were followed for 7 years. The
      diagnostic sensitivity, specificity, and predictive value of thallium
      scintigraphy for the identification of patients having subsequent cardiac events
      during follow-up was calculated. RESULTS: A cardiac event occurred in 41 patients
      during the follow-up period. Presence of both transient and permanent defects and
      abnormal ST-segment responses during thallium scintigraphy were significantly
      associated with an impaired prognosis (P < 0.0001). The highest sensitivity (85%)
      was achieved by the combination of transient defect with or without persistent
      defect and with or without abnormal ST-segment response. The highest specificity
      was provided by a transient defect (90%), and the predictive value of a positive
      test result was 60%. Seventeen of 29 patients with a transient defect had a
      cardiac event during follow-up. Patients with normal test results had excellent
      prognoses; 93% of 82 patients were free of cardiac events during follow-up.
      CONCLUSIONS: Exercise thallium-201 scintigraphy is suitable for long-term risk
      stratification in patients with chest pain and suspected but unconfirmed
      myocardial infarction, because high- and very low-risk subsets can be identified
      at the time of discharge.

PMID- 8269212
TI  - Use of creatine kinase isoforms for diagnosis of infarct artery patency after
      thrombolytic therapy with streptokinase.
AB  - BACKGROUND: We investigated whether the proportion of creatine kinase (CK) MM3 to
      total MM isoform, measured in a single blood specimen taken at 3 hours after
      starting intravenous administration of streptokinase to patients with developing
      myocardial infarction, would give reliable information on patency or occlusion of
      the infarct-related coronary artery. METHODS: Fifty-nine patients received
      streptokinase 1.5 x 10(6) U intravenously within 6 hours of onset of prolonged
      chest pain and ST-segment elevation. Patency of the infarct-related coronary
      artery was assessed by arteriography at 2.6 +/- 0.3 (SD) hours after starting
      streptokinase. Creatine kinase MM isoforms were measured by chromatofocusing in
      blood taken at 3 hours after streptokinase. RESULTS: A proportion of CKMM3 to
      total CKMM of greater than 50% was present in 34 of 34 patients (100%) with a
      patent, infarct-related artery at arteriography and whose peak total CK activity
      reached twice the upper normal limit for our laboratory (600 U/L). CKMM3/total
      CKMM was less than 50% in 14 of 18 patients (78%) in whom the infarct-related
      artery was occluded. In five of six patients with a nondiagnostic total CK rise
      (peak < 600 U/L), 3-hour CKMM3/total CKMM was less than 50% despite a patent
      artery. CKMM3 was not measurable in one patient. CONCLUSIONS: A proportion of
      CKMM3/total CKMM of greater than 50% is highly sensitive for prediction of
      infarct artery patency at 3 hours after administration of streptokinase. However,
      the test used in this way is not reliable for patients with "prevented"
      myocardial infarction. Also, positive tests do occur in patients with
      angiographically occluded arteries, possibly signifying intermittent reperfusion
      and occlusion.

PMID- 8269213
TI  - Photodynamic therapy of vascular stenosis: results from cell culture studies on
      human endothelial cells.
AB  - BACKGROUND: Experimental results from human cell culture studies have shown that
      smooth muscle cells derived from human atherosclerotic plaques react more
      sensitively to photoactivated dihematoporphyrin-ester and -ether (DHE) than
      smooth muscle cells from human nonatherosclerotic arteries. A therapeutic concept
      of photodynamic therapy of vascular stenosis appears, therefore, to be promising.
      The prerequisite for an intravascular application is a relatively harmless
      application of the photosensitizing agent to the luminal lining of endothelial
      cells. METHODS: The effect of DHE with and without photoactivation was examined
      on endothelial cell cultures from human saphenous veins. The cellular uptake of
      DHE in relation to the serum content of the culture medium was evaluated, as well
      as its effect on proliferative activity, cell size, cell volume, and cellular
      viability. RESULTS: Intracellular uptake of DHE decreased significantly when
      higher serum concentrations were present in the culture medium. Incubation of
      cells with the photosensitizer for 9 days in the dark without light activation
      resulted in a significant decrease of endothelial cell proliferation only at
      concentrations higher than 2.5 micrograms/mL (= 2.5 mg/kg body weight for
      systemic application in vivo). Additional photoactivation caused no reduction of
      cell viability at DHE concentrations of 1 microgram/mL, but at 2.5 micrograms/mL
      and 5 micrograms/mL, a reduction of viable cells within 24 hours was observed in
      relation to the energy densities used for irradiation. CONCLUSIONS: Because
      smooth muscle cells from atherosclerotic plaques are, however, much more
      sensitive to photodynamic treatment, the concept of a photodynamic therapy of
      vascular stenosis may provide a good tool in the reduction of restenosis rates
      after recanalization of severely stenosed or even occluded arteries.

PMID- 8269214
TI  - Contributors to cardiac invalidism after acute myocardial infarction.
AB  - Cardiac invalidism is a term used repeatedly in the literature during the past
      few decades, but little attention has been given to studying the variables
      contributing to this phenomenon. Data were collected from 111 patients with first
      acute myocardial infarction. Patients were visited at home 1 month and 4 months
      after hospital discharge. Social support, self-esteem, health perceptions,
      emotional distress, interpersonal dependency, and neuroticism were measured using
      standardized instruments. Illness severity was determined using the Coronary
      Prognostic Index, the Specific Activity Survey, and treadmill testing results.
      Neuroticism and social support were significant predictors of cardiac invalidism
      4 months after myocardial infarction. Illness severity was not a significant
      predictor of cardiac invalidism or return to work. The only significant predictor
      of return to work was health perception. Patients receiving more support than
      desired experienced less cardiac invalidism after acute myocardial infarction.
      Physicians are encouraged not to assume that patients with large infarcts will
      become cardiac invalids. Psychologic recovery may require more than 4 months for
      many patients, but positive messages regarding patient health can influence such
      outcomes. Families and friends should be taught to provide appropriate types and
      amounts of support. The amount of support typically thought to be adequate may
      not be sufficient. Patients who initially receive more support than desired
      experience the best psychologic outcomes. High levels of support need not
      continue indefinitely.

PMID- 8269215
TI  - Bibliography of the current world literature.

PMID- 8269216
TI  - Restenosis: the clinical problem.

PMID- 8269217
TI  - Pharmacologic prevention of restenosis after coronary angioplasty: review of the
      randomized clinical trials.

PMID- 8269218
TI  - New device angioplasty: the impact on restenosis.

PMID- 8269219
TI  - Cellular and molecular mechanisms of coronary artery restenosis.

PMID- 8269220
TI  - Relationship of blood cholesterol and apoprotein B levels to angiographically
      defined coronary artery disease in young males.
AB  - BACKGROUND: Coronary heart disease is mainly caused by the effects of obstruction
      to blood flow in the coronary arteries from discrete mural lesions that encroach
      into the lumen and usually occur in arteries that are involved by
      atherosclerosis. Even though the level of certain lipoproteins is indisputably
      related to the degree of this atherosclerotic involvement of the coronary
      arteries, the question of whether lipoproteins are also associated with the
      obstructive lesions remains uncertain. METHODS: This study addressed the question
      in 53 males (age, 44.6 +/- 4.9 y) with premature coronary heart disease and
      angiographically proven coronary artery disease. The cholesterol, triglyceride,
      high-density lipoprotein, apoprotein B, and apoprotein A-I levels were compared
      by linear correlation to semiquantitative angiographic measures of coronary
      artery disease severity (coronary stenosis score and mean coronary stenosis
      score), the extent of mural involvement (coronary atheromatous score and mean
      coronary atheromatous score), and also the number of normal coronary artery
      segments, an alternative severity score (Jenkins), and left ventricular function
      score. RESULTS: Age, past and present cholesterol, low-density lipoprotein
      cholesterol, and apoprotein B levels correlated directly with the extent of
      disease (r = 0.27, 0.46, 0.29, 0.26, 0.35, respectively, P < 0.05 with coronary
      atheromatous score; r = 0.29, 0.44, 0.33, 0.30, 0.35, respectively, P < 0.05 with
      mean coronary atheromatous score). Age and New York Heart Association angina
      functional class correlated directly with disease severity (r = 0.25, 0.31,
      respectively, P < 0.05 with coronary stenosis score; r = 0.25, 0.34,
      respectively, P < 0.05 with mean coronary stenosis score). There was an inverse
      association between age, past and present cholesterol, low-density lipoprotein
      cholesterol, and apoprotein B levels with the number of normal segments (r = 
      0.23, -0.46, -0.38, -0.35, -0.39, respectively, P < 0.05). Multiple regression
      analysis was undertaken with lipoproteins and age as independent variables and
      angiographic scores as dependent variables; the apoprotein B level was the most
      predictive of the extent of coronary artery disease (P < 0.02) and inversely
      predicted the number of normal segments (P < 0.002). Of those variables entered
      into the regression model, only age was independently predictive of the severity
      of angiographic coronary artery disease. CONCLUSION: Apoprotein B levels are not
      predictive of coronary artery disease severity but do predict independently the
      extent of involvement of coronary atherosclerosis defined angiographically.

PMID- 8269221
TI  - Flow-function dissociation following an acute dose of cocaine: effect of
      captopril on coronary flow.
AB  - BACKGROUND: Acute administration of cocaine leads to left ventricular dysfunction
      and a decrease in coronary blood flow. This experiment studied the relationship
      between function and flow over time in cocaine heart disease and examined the
      effects of captopril on this relationship. METHODS: Dogs anesthetized with
      pentobarbital (n = 13) were given a 3 mg/kg body weight intravenous bolus of
      cocaine followed by a 7 mg/kg infusion over 10 minutes. Animals were then
      randomly assigned to receive either captopril (0.5 mg/kg infused over 5 minutes,
      followed by 0.5 mg/kg/h) or an equivalent volume of saline beginning 15 minutes
      after cocaine administration. Coronary blood flow (radioactive microspheres and
      Doppler flow probes) and left ventricular function (two-dimensional
      echocardiogram and dP/dt) were monitored for 2 hours. RESULTS: Within 15 minutes,
      cocaine caused a drop in dP/dt by 39% to 42% and in coronary blood flow by 35%.
      Cocaine also caused an increase in left ventricular end-diastolic pressures in
      both groups. Cocaine resulted in prolongation of an index of end-diastolic
      isovolumic relaxation time (tau) from a baseline of 34 milliseconds to 56
      milliseconds at 15 minutes after cocaine administration in the control group and
      from a baseline of 35 milliseconds to 49 milliseconds in the captopril group (P <
      0.05). By 2 hours after therapy, the tau in the control group remained elevated,
      whereas in the captopril group it returned toward baseline. At 2 hours of
      observation, systolic function recovered while coronary flow remained depressed.
      There was no difference between the captopril and control groups in coronary
      blood flow or systolic cardiac function at any time during the study.
      CONCLUSIONS: Cocaine caused left ventricular systolic and diastolic dysfunction
      as well as reduced coronary blood flow. At 2 hours there is a dissociation of
      systolic function, which recovers, and of coronary blood flow, which does not.
      Captopril had no effect on coronary blood flow or systolic left ventricular
      function following cocaine administration.

PMID- 8269222
TI  - Amiprilose in the prevention of restenosis after coronary intervention in a swine
      model.
AB  - BACKGROUND: Amiprilose hydrochloride is a synthetic carbohydrate with anti
      inflammatory and antiproliferative properties. This study tested the potential
      benefit of amiprilose in preventing coronary artery restenosis in a swine model.
      METHODS: The swine restenosis model was prepared using Hanford miniature swine
      made atherosclerotic with coronary abrasion, high-fat and high-cholesterol
      feeding, and intracoronary stenting. Eighteen animals were randomized to receive
      amiprilose, 100 mg/kg body weight orally twice per day (n = 9), or no amiprilose
      (n = 9) beginning 5 days before stenting and continuing through 4 weeks until
      sacrifice. Presacrifice quantitative coronary angiography and postsacrifice
      histologic examination revealed the degree of intimal proliferation. RESULTS:
      Coronary angiography revealed no difference in percentage-diameter stenosis
      between the amiprilose and control groups (left anterior descending artery [LAD],
      46% +/- 10% vs 44% +/- 17%; circumflex artery [CFX], 43% +/- 21% vs 42% +/- 15%;
      right coronary artery [RCA], 37% +/- 11% vs 34% +/- 9%; P = not significant
      [NS]), respectively, or in change in lumen diameter from poststenting to
      presacrifice (LAD, -1.0 +/- 0.4 mm vs -1.1 +/- 0.7 mm; CFX, -1.2 +/- 0.8 mm vs 
      1.0 +/- 0.7 mm; RCA, -1.1 +/- 0.4 mm vs -1.0 +/- 0.4 mm; P = NS). Morphometric
      histologic analysis likewise showed no difference in percentage-area stenosis
      (LAD, 55% +/- 14% vs 55% +/- 15%; CFX, 53% +/- 15% vs 54% +/- 12%; RCA, 39% +/-
      17% vs 39% +/- 20%; P = NS) or in maximal intimal thickness. CONCLUSION:
      Amiprilose hydrochloride did not prevent coronary intimal proliferation in this
      swine model of restenosis.

PMID- 8269223
TI  - In vitro model of the inner parts of a vessel wall with cultured human vascular
      cells.
AB  - BACKGROUND: Transfilter culture systems with enzymatically isolated human
      vascular cells were established to imitate the morphologic situation of the inner
      parts of a vessel wall. METHODS: In transfilter cultures, only smooth muscle
      cells were seeded on one side of the filter, whereas in transfilter cocultures,
      smooth muscle cells were cultivated in the presence of confluent or nonconfluent
      (injured) endothelial cells on the other side of the filter. The filter mimics
      the porous internal elastic lamina. Fourteen days after seeding, cultures were
      fixed, embedded in Araldite (Serva, Heidelberg, Germany), and prepared for
      histologic examination (light microscopy, indirect immunofluorescence staining of
      von Willebrand factor- and alpha-smooth muscle actin-antigen). RESULTS: In
      transfilter cultures, smooth muscle cells migrated through the pores to the
      opposite side of the filter, replicated there, and formed fibromuscular
      proliferates (two to four layers of smooth muscle cells). The proliferation rates
      of the smooth muscle cells were similar on both sides of the filter and showed an
      optimum rate on day 4 in culture as determined by 5-bromo-2'-deoxyuridine
      labeling. By cocultivating a confluent endothelial cell layer on one side of the
      filter, migratory activity of smooth muscle cells was inhibited. However, when
      smooth muscle cells were cultivated together with proliferating endothelial cells
      (injured state), proliferation of smooth muscle cells was massively stimulated
      (up to 12 layers of smooth muscle cells). CONCLUSIONS: The results indicate that
      the confluency of the endothelial cells and their proliferation rate influence
      the migratory and proliferative behavior of smooth muscle cells. The transfilter
      system may be a suitable model for prescreening of potential antiproliferative
      and antiarteriosclerotic drugs.

PMID- 8269224
TI  - Late thrombolytic therapy: mechanism of benefit and potential risk among patients
      treated beyond 6 hours.
AB  - BACKGROUND: Thrombolytic therapy is the treatment of choice for many patients
      with myocardial infarction, particularly those presenting to the hospital within
      6 hours from symptom onset. Although prompt treatment promises to provide the
      greatest overall benefit, delayed thrombolysis (possibly beyond a time when
      myocardial salvage is achieved) may also have a role in current clinical
      practice. METHODS: A review of the English-language literature was conducted by
      MEDLINE search. Pertinent references were found as far back as 1912. RESULTS:
      Results of several nonrandomized clinical studies and one recently completed
      randomized study (the Late Assessment of Thrombolytic therapy Efficacy [LATE])
      suggest that thrombolytic therapy may be beneficial up to 12 hours from the onset
      of symptoms. The mechanisms of benefit are poorly defined, but they may include
      myocardial salvage, reduced early infarct zone expansion, improved healing, and
      decreased ventricular irritability. These mechanisms are not necessarily
      exclusive of one another. An increased risk of myocardial rupture and
      thromboembolism may be incurred, limiting the usefulness of treatment with
      further delay. CONCLUSIONS: Delayed thrombolysis (up to and possibly beyond 12
      hours from symptom onset in certain patient subgroups) reduces patient mortality.
      Despite increasing support, however, many patients, even those seeking medical
      treatment within 6 hours, are not being given thrombolytic therapy. Further
      investigation into this area must be undertaken. The Benefits of Late
      Thrombolysis (BOLT) study should provide much needed information.

PMID- 8269225
TI  - Bibliography of the current world literature.

PMID- 8269226
TI  - Preliminary evaluation of laparoscopic herniorrhaphy.
AB  - Since November 1990, 50 laparoscopic herniorrhaphies have been done in 47
      patients (three patients with bilateral repairs), including 31 indirect and 19
      direct inguinal hernias, three of which were recurrent. The 47 patients included
      42 men and five women. Small indirect hernias were treated by plugging the hernia
      orifice with a tightly rolled polypropylene mesh plug. Large indirect, all
      direct, and combined hernias were treated by creating a peritoneal flap and
      stapling a polypropylene mesh screen preperitoneally over the defect. The mesh
      was stapled to Cooper's ligament, iliopubic tract, and transversus abdominous
      arch. Forty-five patients were discharged on the day of surgery and the other two
      within 24 h. The average return to full activity has been two days. The only
      intraoperative complication was an easily controlled trocar site bleeder.
      Postoperatively one minor trocar site infection occurred. One persistent and one
      recurrent hernia were among the group, both large indirect hernias done early in
      our experience (by the plug technique) before stapling instruments were
      available. The technique of laparoscopic herniorrhaphy is in its infancy and
      still evolving as our understanding of anatomy and technology improves. Even if
      long-term follow-up shows an acceptable recurrence rate and less patient
      disability, surgeons must weigh the wisdom of converting a procedure from local
      to general anesthesia and an inexpensive procedure into a more expensive
      procedure.

PMID- 8269227
TI  - Combined laparoscopic incarcerated herniorrhaphy and small bowel resection.
AB  - Laparoscopic femoral herniorrhaphy using a preperitoneal plug and patch appears
      to be a feasible laparoscopic approach to femoral hernia. A modified
      preperitoneal femoral hernia repair with mesh and resection of incarcerated small
      bowel has been successfully completed under laparoscopic guidance in a 64-year
      old patient with incarcerated femoral hernia. To our knowledge, this is the first
      such case reported in the United States. With further experience, laparoscopic
      femoral herniorrhaphy could provide a viable alternative to the standard
      treatment of femoral hernia.

PMID- 8269228
TI  - Laparoscopic fenestration of a lymphocele following combined pancreas-kidney
      transplantation.
AB  - The development of a lymphocele is an uncommon but well-known complication
      following a kidney transplantation. In case of recurrence after puncture and
      aspiration, a laparoscopic procedure seems to be the treatment of choice. For the
      preoperative workup ultrasound is essential; CT scan is to be favored if
      available. A large fenestration is easy to perform laparoscopically and thus the
      lymphocele is drained into the abdominal cavity. Because of the immunosuppressive
      treatment, adhesions hindering a laparoscopic approach are unusual. The
      conclusion is that surgeons trained in laparoscopic techniques have an important
      role in these infrequent abdominal problems.

PMID- 8269229
TI  - Video thoracoscopic dorsal sympathectomy: a new approach.
AB  - With the recent popularization of video laparoscopic cholecystectomy comes a
      renewed interest in thoracoscopy and its clinical applications in intrathoracic
      disease. Successful video thoracoscopic dorsal sympathectomy was accomplished in
      a patient with causalgia of the right upper extremity with immediate and complete
      resolution of pain and vasomotor symptoms. Standard operative approaches to
      dorsal sympathectomy are technically difficult, having risks of major nerve
      injury and Horner's syndrome. Video thoracoscopic dorsal sympathectomy obviates
      these risks and should become the procedure of choice in the future.

PMID- 8269230
TI  - Laparoscopic assisted abdominoperineal resection.
AB  - A technique is described for laparoscopic abdominoperineal resection (APR). Three
      of four such cases could be successfully completed laparoscopically. One major
      complication was directly related to the laparoscopic approach, an enterotomy
      caused by the Babcock clamp, which was discovered at the time of conversion to
      laparotomy for bleeding. A minor complication related to the laparoscopic
      procedure, subcutaneous emphysema, required no treatment. There was one
      postoperative death unrelated to the laparoscopic technique. The intraoperative
      advantage was enhanced visualization; the intraoperative disadvantages were
      increased operative time and cost. Postoperative advantages were earlier
      mobilization, oral intake, and discharge; decreased pain; and improved cosmesis.
      Laparoscopic APR is both feasible and safe and with more experience should prove
      to be cost effective.

PMID- 8269231
TI  - Laparoscopic anterior resection of the rectum using a triple stapled
      intracorporeal anastomosis in the pig.
AB  - Laparoscopic anterior resection of the rectum was performed in the porcine model.
      Colorectal anastomosis was accomplished with a closed triple staple technique
      using a circular stapler. The anvil and shaft were passed beyond the level of
      resection and retrieved through the proximal transverse linear cutter staple
      line. The stapler post was passed through the distal rectal staple line
      transanally. The resulting stapled anastomosis contained portions of three staple
      lines. There were no anastomotic leaks or strictures at one month follow-up
      autopsy. The triple-stapled anastomosis via a laparoscopic approach after an
      anterior resection of the rectum in a pig is a safe, reliable technique.

PMID- 8269232
TI  - Laparoscopic hysterectomy: how should it be done?
AB  - A laparoscopic hysterectomy technique is described using standard acceptable
      surgical technique, and with the primary tool being the Multifire Endo-GIA 30
      stapler (U.S. Surgical Corp., Norwalk, CT, U.S.A.). Unlike the use of
      electrosurgical desiccation, use of this stapler provides a safe and effective
      method that can be used by all laparoscopic surgeons.

PMID- 8269233
TI  - Diagnostic laparoscopy.
AB  - Diagnostic laparoscopy is rapidly becoming a procedure used by general surgeons
      in increasing numbers. Its use will follow the therapeutic procedures now being
      used by many fellow surgeons. As the procedure is generally performed under local
      anesthesia, new techniques must be learned. The indications include abdominal
      pain (acute and chronic), focal liver disease, ascites, preoperative evaluation
      of malignant disease, and second-look evaluations after medical therapy for
      malignant disease. The overall diagnostic rate is 99% for acute abdominal pain,
      70% for chronic pain syndromes, 95% for focal liver disease, 95% for abdominal
      masses, 97% for ascites, and greater than 80% for retroperitoneal disease.
      Diagnostic laparoscopy should be used with increasing frequency when a tissue
      diagnosis is needed.

PMID- 8269234
TI  - Laparoscopic retrieval of a retained surgical sponge: a case report.
AB  - A retained laparotomy pad after abdominal surgery is a complication that usually
      requires a second laparotomy. We report a case in which a laparotomy pad and ring
      were removed laparoscopically 1 week postoperative.

PMID- 8269235
TI  - Postlaparoscopic small bowel obstruction.
AB  - Laparoscopic surgery continues to grow in popularity as a technique for
      approaching a variety of clinical problems. With an increase in the number of
      these procedures performed, unique complications, both early and late, will be
      identified. Optimal management of complications may differ significantly from the
      conventional approach. We describe the course of a patient who develops a high
      grade partial small bowel obstruction 2 days after an uneventful laparoscopic
      cholecystectomy for acute cholecystitis. The patient had a history of
      laparoscopic pelvic surgery 7 years previously. Findings at exploration included
      a Richter's hernia through a midline fascial defect unrelated to our procedure.
      This defect, approximately 5 cm below the umbilicus, was most likely secondary to
      her previous laparoscopic procedure. This finding supports routine fascial
      closure of 10-mm or greater trochar sites and early, aggressive investigation and
      intervention in postlaparoscopic bowel obstructions.

PMID- 8269236
TI  - Carcinoma of a gallbladder polyp: treated by laparoscopic laser cholecystectomy.
AB  - To define the significance of polyps of the gallbladder, we undertook a
      retrospective review of all gallbladders removed over a 10-month period in our
      institution. The discovery of polyps are usually incidental and treated as
      benign. Polyps can form because of cholecystitis, cholesterolosis, hypertrophy of
      the epithelial lining (adenoma or papilloma), or carcinoma. Of 461 gallbladder
      specimens, 12 had polyps with one containing carcinoma, and two more specimens
      had carcinoma. All but one case were treated by laparoscopic cholecystectomy.
      Herein is described a case of a symptomatic patient presenting with a 1.1-cm
      polyp treated by laparoscopic laser cholecystectomy. An aggressive approach for
      gallbladder polyps with laparoscopy is proposed, especially in symptomatic
      patients or for polyps larger than 1 cm.

PMID- 8269237
TI  - False-positive ultrasonography in agenesis of the gallbladder: a pitfall in the
      laparoscopic cholecystectomy approach.
AB  - We report a case of agenesis of the gallbladder in a 15-year-old girl incorrectly
      diagnosed as cholelithiasis on preoperative sonography and suspected at
      laparoscopic surgery. The diagnosis of agenesis was confirmed at open surgery
      with intraoperative sonography, intraoperative cholangiography, and postoperative
      radioisotope scan. Difficulties in preoperative diagnosis and the management
      during laparoscopic and open surgery are discussed.

PMID- 8269238
TI  - Laparoscopic, wire-guided insertion of biliary T-tubes.

PMID- 8269239
TI  - Laparoscopically assisted resection of intussuscepted Meckel's diverticulum.
AB  - We report a case of a Meckel's diverticulum with pancreatic heterotopia that had
      intussuscepted into the distal ileum, masquerading as a small bowel tumor and
      presenting with acute lower gastrointestinal hemorrhage. Laparoscopically
      assisted resection of the diverticulum was successfully accomplished.

PMID- 8269240
TI  - Laparoscopically assisted ileocolectomy in Crohn's disease.
AB  - Laparoscopically assisted intestinal surgery has been described in a variety of
      different intestinal diseases but not in inflammatory bowel disease. The study
      shows that laparoscopically assisted ileocolectomy is feasible in patients with
      Crohn's disease with low morbidity.

PMID- 8269241
TI  - Laparoscopically assisted colectomy.
AB  - We present 20 cases of laparoscopically assisted colon resection. Ten patients
      were operated on for various benign lesions of the large bowel, and the remaining
      10 for malignancy. Three fourths of the patients were over 65 years of age. The
      operative technique described herein involved laparoscopic mobilization of the
      colon and then its delivery through a relatively small incision through the
      anterior abdominal wall. Direct mobilization of the segment of bowel containing
      the malignant lesion was usually accomplished via the accessary incision made
      directly over the lesion. After eviscerating the specimen onto the abdominal
      wall, the involved segment of large intestine was resected along with its
      accompanying mesentery. The anastomosis was done by conventional linear stapling
      devices. No operative-related mortality occurred. Postoperative nasogastric tube
      suction was required in only one patient. Return of gastrointestinal function
      occurred an average of 2.5 days after the surgery. Average postoperative hospital
      stay was less than 5 days.

PMID- 8269242
TI  - Laparoscopic Doderlein hysterectomy: a rational alternative to traditional
      abdominal hysterectomy.
AB  - Nearly three of four hysterectomies are performed by abdominal incision. When
      laparoscopically directed dissection of the uterus adnexae and development of the
      bladder flap are coupled with a Doderlein vaginal hysterectomy, most of these
      abdominal procedures can be converted to vaginal procedures. Experience with 167
      procedures has demonstrated that this new procedure can be performed safely,
      effectively, and efficiently. The benefits of less postoperative discomfort,
      resulting in shorter hospital stays and quicker return to normal activity,
      coupled with a reduced cosmetic defect, have been clearly demonstrated.

PMID- 8269243
TI  - Laparoscopic cholecystectomy: comparison of university and community experience.
AB  - We compared the first year's experience in performing laparoscopic
      cholecystectomy in a university hospital and a community hospital to determine
      the impact of postgraduate surgical training on outcome. Laparoscopic
      cholecystectomy was attempted on 446 patients. The conversion rate to open
      cholecystectomy was 8.3% and did not differ between institutions. Surgical house
      staff performed 43% of the cases at the university hospital compared with 8% at
      the community hospital. The greater use of laser and cholangiograms resulted in
      significantly longer mean operative time at the university hospital (141 +/- 26
      min) than at the community hospital (114 +/- 52 min). The overall complication
      rate did not differ significantly (p = 0.15). Complications included common duct
      injury (three cases), bile leak (five cases), bleeding or hematoma (six cases),
      epigastric artery hematoma (one case), and death (one case). Operative
      inexperience during this first year may be a major determinant for the
      complication rates at both hospitals. It is too early to determine the impact of
      graduate surgical education on complications. Intense education and supervised
      instruction is requisite to minimizing the morbidity associated with laparoscopic
      cholecystectomy regardless of whether it is performed at a university or
      community hospital.

PMID- 8269244
TI  - Pancreas divisum: observation, endoscopic drainage, and surgical treatment
      results in 65 patients.
AB  - Sixty-five patients with symptomatic pancreas divisum were treated by endostents,
      surgery, or observation. In 35 patients, endoscopic stenting either alone (20) or
      followed by surgery (15) was the primary therapy. Of 30 patients not stented, 10
      underwent elective surgery and 20 were followed. Treatment was based on symptoms
      and biochemical and radiologic tests. The results of surgical decompression
      correlated favorably with endoscopic drainage. In untreated patients, the natural
      history of pancreas divisum was benign. Surgery is safe and effective in
      symptomatic patients, although multiple operations may be required for recurrent
      symptoms or progressive disease.

PMID- 8269245
TI  - Scintigraphic evaluation of biliary leakage following laparoscopic
      cholecystectomy.
AB  - Three patients with biliary leakage following coelioscopic cholecystectomy after
      percutaneous drainage of abdominal collection underwent 99m Tc TRIMETHYL-BROMO
      IDA biliary scintigraphy. In all cases, scintigraphy showed the site of the leak
      with a good dynamic evaluation of tracer confirming the adequacy of percutaneous
      drainage. Two patients were treated conservatively; one underwent surgical repair
      of a common bile duct lesion because of the high output of bile despite
      nasobiliary drainage. Biliary scintigraphy provides useful information in case of
      suspicious biliary leakage after coelioscopic cholecystectomy.

PMID- 8269246
TI  - Does routine cystic duct cholangiogram during laparoscopic cholecystectomy
      prevent common bile duct injury?
AB  - Between November 1989 and September 1992, the author performed 1,000 laparoscopic
      cholecystectomies. Three common bile duct injuries occurred (0.3%). Selective
      cystic duct cholangiograms were performed for diagnosis and management of common
      bile duct stones. A total of 102 cholangiograms (10%) were done. Only eight of
      these cholangiograms were done for anatomical verification in the face of severe
      chronic or acute cholecystitis. Five were cystic duct cholangiograms, resulting
      in two common bile duct injuries. To avoid the problem of common bile duct injury
      in cases of obscure anatomy where clarification was needed, a
      cholecystocholangiogram was done for duct identification in three subsequent
      cases without event. The third common bile duct injury occurred early in the
      learning experience without benefit of the cholangiogram.

PMID- 8269247
TI  - Risks of blind versus open approach to celiotomy for laparoscopic surgery.
AB  - Patients undergoing laparoscopic cholecystectomy had celiotomy either by a blind
      (Veress needle) approach (n = 781) or by fascial and peritoneal incision with
      insertion of a 10-mm sheath under direct vision (n = 247). The blind approach was
      associated with three small bowel injuries and one tear of the left common iliac
      artery. No intestinal or vascular injuries occurred in the open insertion group.
      The difference was not statistically significant. The mean duration of surgery
      was 81.4 +/- 1.3 min in the blind group compared with 72.6 +/- 2.0 min in the
      open group (p < 0.001). There was no significant difference in postoperative stay
      or in return to normal activity between the two groups. It is recommended that
      blind access to the peritoneal cavity for laparoscopy be abandoned in favor of an
      open approach because the blind approach confers no advantages and places the
      patient at risk for unrecognized visceral or vascular injury even though these
      injuries may not occur at a statistically significant frequency.

PMID- 8269248
TI  - Retroperitoneal endoscopic adrenalectomy: an experimental study.
AB  - Laparoscopic approaches to adrenalectomy have been limited by the retroperitoneal
      (RP) location of the adrenal glands and their relative inaccessibility
      transabdominally. We developed a technique for endoscopic adrenalectomy in a
      domestic swine model using insufflation of the RP space with CO2 and
      retroperitoneoscopy. The technique for retroperitoneal endoscopic adrenalectomy
      was first developed in an acute study of three animals. A chronic survival study
      was then undertaken in six pigs. Unilateral right (n = 3) or left (n = 3)
      adrenalectomy was performed. Mean RP insufflation time was 14.5 min (range, 7-30
      min), and mean dissection time after insufflation was 100 min (range, 80-120
      min). Two additional animals died under anesthesia after RP insufflation and
      placement of the trocars for retroperitoneoscopy but before dissection of the
      adrenal gland. One death was unexplained at autopsy. The other death was
      associated with a right-sided pneumothorax attributable to penetration of the
      diaphragm by a trocar. The remaining six pigs recovered uneventfully from the
      procedure. Autopsies performed 37 to 51 days postoperatively showed minimal
      scarring of the adrenalectomy bed. The results suggest that posterior
      adrenalectomy using RP CO2 insufflation and direct retroperitoneoscopy is
      potentially applicable to the treatment of small adrenal lesions in humans.

PMID- 8269249
TI  - Transvaginal removal of gallbladders with large stones after laparoscopic
      cholecystectomy.
AB  - Very large gallstones sometimes render laparoscopic cholecystectomy time
      consuming and difficult. In addition, several advantages of laparoscopy, namely
      decreased postoperative pain and minimal abdominal scarring, could be compromised
      by the need to enlarge the umbilical incision. Besides the solution of the
      mechanical or electrohydraulic fragmentation of such large gallstones, as
      described by several authors, we propose a posterior colpotomy as a simple
      technique for removing very large gallbladders in women.

PMID- 8269250
TI  - Laparoscope-guided enterolithotomy for gallstone ileus.
AB  - Two women, both aged 76 years, with several days of clinical symptoms of
      mechanical intestinal obstruction were diagnosed laparoscopically and found to
      have gallstone ileus. In one patient, pneumobilia was demonstrated preoperatively
      on plain abdominal radiography. Neither patient had had previous abdominal
      surgery. After searching through the small intestine laparoscopically, the stones
      were found. The site of obstruction was in both cases the ileum. The nondistended
      small intestine was visualized in the videoendoscope and lifted toward the
      anterior wall. Through very small lower midline and right lower quadrant muscle
      splitting incisions, respectively, the ileum, including the gallstone, was
      brought out extracorporally, and the stone was removed by a simple
      enterolithotomy. Both patients recovered rapidly and returned to their homes on
      the fourth and fifth postoperative days, respectively. One patient returned after
      3 weeks and was successfully treated for a wound infection. Four months after
      surgery, neither patient had any abdominal complaints. Laparoscopic diagnosis,
      and if possible treatment for mechanical intestinal obstruction, especially in
      elderly nonoperated patients, is suggested to minimize operative trauma,
      facilitate postoperative mobilization and hopefully reduce the high operative
      morbidity and mortality in this group of patients.

PMID- 8269251
TI  - Simulated operations by pulsatile organ-perfusion in minimally invasive surgery.
AB  - The rapid amplification of indications and areas of application of laparoscopic
      or thoracoscopic techniques leads to increasing problems and needs in surgical
      training. Pulsatile perfusion of organs (POP) and organ groups in laparoscopic
      training devices (pelvitrainers) aids in creating optimum conditions for the
      simulation of difficult intraoperative situations and complications. Simple
      applicability, low cost, and the possibility of a noticeable reduction of the
      currently required animal experiments render POP an ideal training method for
      minimally invasive surgery.

PMID- 8269252
TI  - Lost intraperitoneal stones after laparoscopic cholecystectomy: harmless sequela
      or reason for reoperation?
AB  - Laparoscopic cholecystectomy has become the "gold standard" in the therapy of
      noncomplicated cholelythiasis. Gallbladder perforation with bile and calculi
      spreading in the abdominal cavity is one of the most frequent intraoperative
      complications of laparoscopic cholecystectomy. When not recognized during surgery
      or unproperly treated, it may lead to intraperitoneal abscess formation and may
      require a reoperation. We report a case of an intraperitoneal abscess with a
      cutaneous fistula, a site of a mucopurulent exudate, and stone spillage after an
      unrecognized gallbladder perforation and residual lithiasis in the peritoneal
      cavity found 3 months after laparoscopic cholecystectomy.

PMID- 8269253
TI  - Distal thermal injury from monopolar electrosurgery.
AB  - Lysis of infrahepatic adhesions during laparoscopic cholecystectomy was attempted
      by using monopolar electrocautery. The flow of current was seen to follow an
      unpredictable pathway and almost causing a thermal injury to an adjacent small
      bowel loop. A brief discussion of pertinent bioelectrical principles is also
      presented.

PMID- 8269254
TI  - Transabdominal preperitoneal herniorrhaphy.
AB  - There have been multiple different approaches to laparoscopic herniorrhaphy with
      a tendency toward exposure of the preperitoneal space with placement of a
      prosthesis into this area. The transabdominal preperitoneal (TAPP) approach is a
      reasonably simple, safe repair, resulting in a less than 1% recurrence rate with
      minimal complications. This relatively pain-free herniorrhaphy allows rapid
      return to normal activity.

PMID- 8269255
TI  - Simultaneous laparotomy and intraoperative endoscopy for the treatment of high
      jejunal membranous stenosis in a 1-year-old boy.
AB  - A 1-year-old boy with high jejunal membranous stenosis was successfully treated
      "a minima" by antimesenteric longitudinal enterotomy over the diaphragm, excision
      of the latter, and transverse closure of the bowel. This was made possible by use
      of simultaneous peroperative endoscopy, which allowed exact localization of the
      diaphragm. Peroperative endoscopy is a useful and accurate method for this
      purpose and should be considered in similar cases.

PMID- 8269256
TI  - Agenesis of the gallbladder: laparoscopic diagnosis.
AB  - Congenital absence of the gallbladder is an extremely rare anomaly. Although
      ideally gallbladder agenesis should be diagnosed before surgery, this has not
      been documented in the literature. Laparoscopy offers patients with
      nonvisualizing or shrunken gallbladders on imaging studies the opportunity for
      diagnosis in a minimally invasive manner. A thorough laparoscopic exploration and
      cholangiogram are necessary to confirm the diagnosis.

PMID- 8269257
TI  - Nerve injury during laparoscopic inguinal hernia repair.
AB  - This report presents a case of injury to the lateral cutaneous nerve of the thigh
      during laparoscopic inguinal hernia repair. Both this nerve and the femoral
      branch of the genitofemoral nerve are at risk during laparoscopic inguinal hernia
      repair. Pertinent anatomy is reviewed and suggestions made to prevent this
      injury. This case does not appear to be an isolated event, and hopefully this
      report will bring attention to this potential complication.

PMID- 8269258
TI  - Two unusual hemorrhagic complications during laparoscopic cholecystectomy.
AB  - Two cases are presented that illustrate unusual hemorrhagic complications during
      laparoscopic cholecystectomy. Both areas of bleeding were at a significant
      distance from the operative site. One was a subcapsular hematoma over the dome of
      the right lobe of the liver, the other a liver capsule tear on the inferior right
      lobe. No bleeding was evident at the time of surgery. These complications appear
      to be an inherent part the laparoscopic method, as they would undoubtedly be
      recognized and treated during an open cholecystectomy. Etiology, prevention,
      recognition, and treatment are discussed.

PMID- 8269259
TI  - Laparoscopically assisted resection of small bowel injury during laparoscopic
      cholecystectomy.
AB  - A patient with previous appendectomy and diagnostic laparoscopy underwent
      elective laparoscopic cholecystectomy. At the conclusion of the procedure, a
      small bowel trocar injury was identified. Resection and anastomosis were
      performed extracorporally via the umbilical incision. The patient was discharged
      on the third postoperative day.

PMID- 8269260
TI  - Minimal invasive surgery for treatment of enlarged symptomatic liver cysts.
AB  - Congenital solitary liver cysts are a common finding, but they are usually
      asymptomatic; however, symptoms occur in about 16% and then require treatment.
      Ideally, complete or partial resection of the cyst is the treatment of choice but
      always implies invasive surgery. We report the case of a 50-year-old woman
      suffering from a massively enlarged cyst in the left liver lobe. We decided to
      resect the extraphepatic part of the cyst by laparoscopic surgery. The patient
      was discharged absolutely asymptomatic 3 days following surgery. We conclude that
      open resection of symptomatic congenital liver cysts should be replaced by
      laparoscopic removal when cysts are mostly extrahepatically located. The
      laparoscopic procedure combines the advantages of minimal invasive surgery with
      the demand for a radical effective treatment.

PMID- 8269261
TI  - Laparoscopic splenectomy: clinical experience and the role of preoperative
      splenic artery embolization.
AB  - We describe the clinical course of 12 patients who underwent laparoscopic
      splenectomy. Two patients were converted to open surgery--the first patient in
      the series because of a hemorrhagic incident and the eighth, who had a 34-cm
      spleen, because of dissection difficulties. The remaining patients had no
      mortality, and perioperative morbidity was 10%. After an average postoperative
      stay of 3.5 days (range, 2-9), most patients were able to resume normal
      activities < or = 2 weeks. Use of preoperative splenic artery embolization was
      begun with the third patient. The technique involved embolization of the spleen
      with coils placed proximally; and contour emboli, absorbable gelatin sponge, and
      small coils placed distally, taking care to spare vessels to the tail of the
      pancreas. A good linear correlation was established between operative blood loss
      and the percentage of splenic devascularization by preoperative splenic artery
      embolization (r - 0.8084). Laparoscopic splenectomy is becoming the preferred
      technique for elective removal of a normal sized or moderately enlarged spleen (<
      20 cm long) when hematologic indications are present.

PMID- 8269262
TI  - Laparoscopic inguinal herniorrhaphy: an individualized approach.
AB  - Between March 1991 and December 1992, we treated 63 patients with symptomatic
      inguinal hernias using a laparoscopic transabdominal preperitoneal approach
      adapted from Nyhus' technique. Treatment was individualized according to the
      classification of groin hernias described by Nyhus. We treated 32 type II hernia
      defects (indirect hernia) by preperitoneal closure of the internal ring with two
      to four stitches of 0-Prolene. Eighteen type IIIA (direct), three type IIIB
      (large indirect with weak posterior wall), and 10 type IV (recurrent) hernias
      were treated by fixing a prolene mesh with 0-Prolene sutures and staples from the
      pubic tubercle medially to the lateral aspect of the internal ring (including the
      cord into the mesh) laterally. The mesh was secured to the transversalis fascia
      and muscle and inferiorly to Cooper's ligament. No peroperative complications
      occurred. One patient had testicular pain of 1 week's duration after treatment of
      a type IV hernia. No mortality was recorded. Patients took, on an average,
      parenteral analgesia once (range, 0-5) and two enteral analgesics (range, 0-6).
      With a median follow-up of 8 months (range, 1-21), no recurrences were noted.
      Results are encouraging, and longer follow-up will determine the long-term
      efficacy of this procedure.

PMID- 8269263
TI  - Laparoscopic rectopexy.
AB  - Laparoscopic rectopexy has been performed in four female patients with rectal
      prolapse. Four or five trocars were used in each case, with the same introduction
      places as for laparoscopic anterior resection. After dissecting the rectum free,
      a polypropylene mesh was introduced and fixed to the promontorium with an
      endoscopic stapler device, and then sutured to the rectum leaving a fourth of the
      anterior rectal wall free. The average operating time was three hours and the
      hospital stay six days. No constipation has been observed postoperatively in the
      patients with preoperative normal bowel habit. The introduction of laparoscopic
      rectopexy opens the possibility of performing different fixation techniques for
      various functional problems in the pelvis, offering a significant decrease in
      morbidity.

PMID- 8269264
TI  - Ojigi tying spatula: a newly developed movable spatula for laparoscopic ligation.
AB  - We developed a new type of movable tying spatula for ligation of the cystic duct
      and artery in laparoscopic cholecystectomy. This spatula can be used to ligate
      any vascular or ductal structure before laparoscopic resection. This instrument
      should give strong support to surgeons performing laparoscopic procedures and
      eventually will replace the expensive clips and Endoloops.

PMID- 8269265
TI  - Laparoscopic nephroureterectomy for end-stage reflux nephropathy in a child.
AB  - End-stage renal disease secondary to vesicoureteral reflux often necessitates
      removal of the affected kidney and its refluxing ureter. Advances in laparoscopic
      techniques have made nephroureterectomy through the laparoscope possible in a
      minimally invasive way. We describe our surgical steps for laparoscopic
      nephroureterectomy in all 11-year-old girl with end-stage reflux nephropathy.
      Reduced trauma of surgical access, minimal postoperative morbidity, shorter
      hospital stay, and minimal scarring make laparoscopic nephroureterectomy a
      comparatively desirable surgical approach, especially in pediatric patients.

PMID- 8269266
TI  - Laparoscopic stenting for protection of common bile duct sutures.
AB  - Laparoscopic common bile duct exploration is comparable with the open operation
      and it is usually finished with the insertion of external bile drainage such as a
      T-tube. We performed an antegrade placement of a biliary stent with primary
      suture of the common bile duct following common bile duct exploration. We thereby
      avoided the acquisition of the additional expensive equipment required for the
      transcystic approach and the placement of a T-tube, which in our eyes contradicts
      the idea of minimized discomfort in minimally invasive surgery.

PMID- 8269267
TI  - Current techniques in laparoscopic appendectomy.
AB  - An improved technique for laparoscopic appendectomy based on an experience of >
      120 cases is presented. This method includes numerous additions to and
      modifications of previously described techniques and is effective for gangrenous
      and perforated appendicitis as well as for less severe cases. The most important
      elements are that (a) it is a safer procedure for attaining insertion of the
      Veress needle and the primary trocar; (b) it employs electrocautery to separate
      the appendix from the mesoappendix; (c) an Endosac can be used for removal of the
      appendix from the abdomen without contamination of the abdominal wall; (d) no
      laser is necessary; and (e) staples are rarely necessary.

PMID- 8269268
TI  - Making loops in laparoscopic surgery: state of the art.
AB  - Premade chromic gut ligating Endoloops used in laparoscopic surgery are not
      always available. Handmade knots or loops, however, are equally effective,
      simpler, cheaper, and readily available. Techniques of making more than 10
      handmade knots and loops are described and illustrated, and their uses are
      discussed. The thread can be introduced inside the abdominal cavity to loop
      around the proposed structure grasped by forceps, brought outside the abdomen,
      tied externally, and the knot pushed and tightened inside by pusher rod. Or, the
      knot may be fashioned outside the abdomen and introduced as a ready-made loop and
      tightened inside by a grasper.

PMID- 8269269
TI  - Colonoscopically assisted intracorporeal laparoscopic wedge resection of a benign
      right colon lesion.
AB  - We present a case of colonoscopically assisted intracorporeal laparoscopic wedge
      resection of a benign right colon lesion. The operative technique is described
      and the rationale discussed with reference to current literature.

PMID- 8269270
TI  - Abdominal wall abscess due to spilled gallstones.
AB  - Spillage of gallstones during laparoscopic cholecystectomy is not a rare event.
      We describe a patient who showed signs of an abdominal wall abscess 4 months
      postsurgery. The abscess was found to be due to gallstones trapped in the
      preperitoneal space behind the left rectus sheath.

PMID- 8269271
TI  - Migration and slipping of metal clips after celioscopic cholecystectomy.
AB  - Most surgeons performing in laparoscopic cholecystectomy have opted for the use
      of metal clips to secure the cystic duct before division. Accordingly, we have
      been using double proximal clipping of the cystic duct for our patients. Certain
      disadvantages of clips are well known, among them, their ability to slip. We
      report one case of clip migration into the common bile duct, which led to
      obstructive jaundice. The clip was recovered after endoscopic sphincterotomy.
      Slipping of the second metal clip lead to biliary peritonitis necessitating
      surgical drainage. The case presented raises the question of whether suture
      ligation of the proximal end of the cystic duct should be preferred to clipping.

PMID- 8269272
TI  - A technique for needle insufflation in obese patients.
AB  - Creation of pneumoperitoneum as the first step in closed laparoscopy and the
      insertion of a primary trocar are the only "blind" steps in laparoscopy. These
      steps have occasionally been associated with technical difficulties and
      complications and with prolonged operative time. These problems are compounded in
      obese patients. In this report, we describe a simple and safe technique for
      needle insufflation and insertion of a primary trocar. With this technique,
      instead of lifting and elevating the anterior abdominal wall by grasping the skin
      and panniculus adiposus with hands or tennaculae, the abdominal fascia is grasped
      with two Kocher clamps and then lifted and held immobile during needle and trocar
      insertion. This maneuver provides much better visual and tactile control and is
      done more expeditiously, particularly in obese patients.

PMID- 8269273
TI  - Is laparoscopic cholecystectomy without intraoperative cholangiography a safe
      operation?

PMID- 8269274
TI  - Detection of low copy numbers of Epstein-Barr virus by in situ hybridization
      using nonradioisotopic probes prepared by the polymerase chain reaction.
AB  - A highly sensitive in situ hybridization procedure was established using
      digoxigenin-11-dUTP-labeled probes that were prepared by the polymerase chain
      reaction (PCR). By using 12 sets of primers, BamHI-W fragment of the Epstein-Barr
      Virus (EBV) was amplified with labeled substrate in individual PCRs. Then the 12
      probes (average size, 120 base pairs) were mixed and hybridized with cultured and
      RNase-treated Namalwa cells, which contain two copies of EBV genomes per cell.
      The strength of the signals was much stronger as compared with random-primed
      probe. Our results indicate that the size-averaged PCR probes magnified the
      sensitivity for detecting low copy numbers of virus genomes by in situ
      hybridization and that this technique has the potential for investigating latent
      virus infection in other clinical situations.

PMID- 8269275
TI  - Absence of cytomegalovirus in gestational tissue in recurrent spontaneous
      abortion.
AB  - There have been conflicting reports regarding the association of cytomegalovirus
      (CMV) and recurrent spontaneous abortions. It is difficult to assess the role of
      CMV in the endometrium by histology alone, since the characteristic cytomegalic
      virocytes are often scarce or absent in this site. Our purpose was to use the
      polymerase chain reaction (PCR) to detect cytomegalovirus in gestational tissue
      of women with recurrent spontaneous abortions. DNA was extracted from 25 samples
      of paraffin-embedded, formalin-fixed gestational tissue from 21 women with at
      least three unexplained spontaneous abortions (mean, 3.4). DNA from an unstained
      paraffin section of each specimen was amplified using nested, multiplex PCR
      specific for the late antigen and the major immediate early genes of CMV. The
      assay used has a demonstrated level of sensitivity on the order of 10(-2)
      virocytes per square centimeter of 4-microM paraffin section. Intact DNA was
      successfully isolated from 21 specimens in 18 patients. Histologic features of
      CMV infection were completely absent from these cases, and none of these
      specimens contained evidence of cytomegalovirus DNA. These findings suggest that
      CMV infection of gestational tissue is not a common direct cause of recurrent
      spontaneous abortions.

PMID- 8269276
TI  - Construction of overlapping oligonucleotide templates for the production of cRNA
      standards for quantitative reverse transcription polymerase chain reaction.
AB  - The reverse transcriptase polymerase chain reaction (PCR) is a technique for the
      study of gene expression that requires far less RNA for analysis than Northern
      blots. The inclusion of cRNA standards in the initial reverse transcription step
      is a way to control for the tube-to-tube variation often inherent in the
      technique and to permit quantitation of the starting amount of the native mRNA
      being analyzed. We describe a method using overlapping oligonucleotides to
      produce templates for the production of cRNA standards for up to three different
      mRNA species. The first step is the synthesis of a pair of overlapping
      oligonucleotides each of which encodes, respectively, sequences analogous to
      either sense or antisense primers for the PCR amplification of up to three
      different messages. These oligonucleotides are designed to have complementary 3'
      ends which permit spontaneous annealing and allow subsequent mutually priming
      extension of the annealed double-stranded portion by T7 DNA polymerase. The T7
      and SP6 RNA polymerase promoters are then added to the ends of the template using
      standard PCR techniques. Once the template is assembled, T7 and SP6 RNA
      polymerases are used to produce copious quantities of cRNA standards and
      controls. This technique can be used to construct multiple cRNA standards for
      essentially any messages of interest. Production of cRNA by a single T7 RNA
      polymerase reaction yields standards sufficient for several thousand separate
      reverse transcriptions.

PMID- 8269277
TI  - Nonspecific in situ hybridization reaction in neuroendocrine cells and tumors of
      the gastrointestinal tract using oligonucleotide probes.
AB  - Oligonucleotides used in in situ hybridization (ISH), regardless of their
      sequence specificity, bind to neuroendocrine (NE) cells in normal
      gastrointestinal mucosa and tumors. This nonspecific binding, presumably related
      to the presence in NE cells of hidden NH2 groups of obscure origin, can be
      prevented by acetic anhydride treatment of the sections. This is a routine step
      in several ISH protocols but not in all. This study emphasizes the need to
      establish safe protocols and controls to check the specificity of ISH procedures.

PMID- 8269278
TI  - Immature teratomas of different origin carried by a pregnant mother and her
      fetus.
AB  - We describe the case of a pregnant mother and her fetus who both carried
      teratomas during the pregnancy. The fetus was diagnosed at 38 weeks' gestation to
      have an intracranial mass, which was later determined to be an immature teratoma.
      During a cesarean section delivery, an ovarian tumor was found in the 27-year-old
      mother that was also diagnosed to be an immature teratoma. Because of the similar
      histology of the tumors carried by both mother and child, a single clonal origin
      was suspected. Using polymerase chain reaction (PCR) and electrophoresis of
      highly polymorphic DNA satellite sequences, we determined that the origin of the
      intracranial teratoma carried by the child was independent of the mother's tumor.
      We also examined the p53 tumor suppressor gene in constitutional cells from both
      mother and child for the possible presence of a cancer-predisposing inherited
      mutation, but none was found. To our knowledge, this is the first report of the
      simultaneous occurrence of independent malignant immature teratomas in a mother
      and child during pregnancy.

PMID- 8269279
TI  - A new procedure for cell lineage determination in acute leukemias.
      Myeloperoxidase mRNA detection.
AB  - Determination of cell lineage in acute leukemias is essential for diagnosis and
      treatment. Detection of myeloperoxidase (MPO) mRNA establishes myeloid lineage of
      leukemic blasts that may be too primitive to be identified as myeloblasts based
      on morphology, cytochemistry, or immunophenotype. A highly specific and sensitive
      new procedure for MPO mRNA detection has been developed using HL-60 cells. It
      involves a microprocedure for total cellular RNA extraction, reverse
      transcription, and specific amplification of target sequences in the resulting
      MPO cDNA, by the polymerase chain reaction. Specific primers are designed to
      amplify an 89-base pair (bp) sequence from the signal peptide, 179 and 318-bp
      sequences from the start and end, respectively, of the heavy-chain sequence, and
      a 255-bp sequence overlapping the proregion and light chain. The correct-size
      amplification products, detected electrophoretically, demonstrate MPO mRNA
      expression in the leukemic cells analyzed. The sensitivity of this new procedure
      was evaluated on serial concentrations of HL-60 cells and was found to be 10
      10(4) cells depending on the MPO cDNA amplified sequence. No amplification
      products were obtained using peripheral blood lymphocytes as a negative cellular
      control. The specificity of the procedure is demonstrated by Southern blotting
      and hybridization with 32P-labeled oligonucleotide probes specific for each of
      the amplified sequences. An additional advantage of this procedure is
      availability of results in 8-24 h, compared with 1-2 weeks for conventional RNA
      methods.

PMID- 8269280
TI  - Reverse transcription-polymerase chain reaction phenotyping of metalloproteinases
      and inhibitors involved in tumor matrix invasion.
AB  - The matrix metalloproteinase enzymes have been implicated in tumor invasion and
      metastasis by a series of correlative immunohistochemical studies. In addition,
      direct evidence for the role of these enzymes in this pathologic process comes
      from studies using specific metalloproteinase inhibitors to block tumor invasion
      and metastasis formation, both in vitro and in vivo. Synthetic oligonucleotide
      primers for four metalloproteinases (MMP-1, MMP-2, MMP-9, MMP-10) and their
      tissue inhibitors (TIMP-1, TIMP-2) were selected, synthesized, and optimized in
      the reverse transcriptase-polymerase chain reaction (RT-PCR) to study the
      qualitative profile of these enzymes and inhibitors in cultured human tumor cells
      and tumor tissues. These primers are specific and generate unique amplification
      products for each appropriate enzyme and inhibitor. Slight enhancement in the
      amplification of cDNA products was achieved by adding dimethylsulfoxide to the
      reaction mixture, but commercial enhancement reagents were ineffective. Using
      this RT-PCR method, cDNA amplification was successful with RNA from as few as 20
      cultured tumor cells. The RT-PCR analysis was done on three invasive human colon
      adenocarcinomas and their paired adjacent normal mucosa. The results show MMP-1
      and MMP-2 products in all three tumors, and MMP-2 detected in one of the three
      normal mucosa samples; TIMP-2 expression was present in two of three patients and
      awaits quantitative assessment of RT-PCR products.

PMID- 8269281
TI  - Expression pattern of metalloproteinases and their inhibitors changes with the
      progression of human sporadic colorectal neoplasia.
AB  - Several studies have implicated the extracellular matrix-degrading
      metalloproteinases (MMPs) as essential agents in tumor cell invasion and
      metastasis. In the present study, we have investigated the patterns of expression
      of a number of MMPs and their specific tissue inhibitors (TIMP-1 and TIMP-2) in
      human colonic tissue samples that represent various stages of progression from
      adenomas showing different degrees of dysplasia to adenocarcinomas. We assessed
      levels of mRNA by Northern blot analysis and the results were measured
      semiquantitatively by densitometry. In total, we analyzed nine adenomas of
      varying size and with varying degrees of dysplasia, three adenomas with
      adenocarcinoma (malignant polyps), and five adenocarcinomas. Although expression
      of MMP and TIMP mRNA was highly intercorrelated, transcripts for stromelysin 3
      and TIMP-2 (high) showed the strongest relation to the neoplastic process.
      Detection of stromelysin 3 mRNA accompanied a diagnosis of severe dysplasia or
      malignancy, whereas levels of TIMP-2 (high) mRNA transcripts permitted finer
      distinctions on the neoplastic continuum. These data indicate changes within
      extracellular matrix acquired during the process of malignant transformation of
      human sporadic colorectal neoplasia.

PMID- 8269282
TI  - Loss of heterozygosity detected in formalin-fixed, paraffin-embedded tissue of
      colorectal carcinoma using a microsatellite located within the deleted in
      colorectal carcinoma gene.
AB  - We determined loss of heterozygosity from formalin-fixed, paraffin-embedded
      tissue of colorectal carcinoma using microsatellite polymorphism. The
      polymorphism was assayed based on DNA amplification by the polymerase chain
      reaction (PCR). The PCR-analyzed microsatellite method was applied to assay
      degraded DNA extracted from paraffin-embedded blocks with adenocarcinoma of
      colon. The DNA from 26 tumors as well as their corresponding normal tissue
      samples were successfully amplified using a dinucleotide microsatellite located
      within an intron of the deleted in colorectal carcinoma gene. Allele losses on
      this marker were detected in 33% of informative colorectal carcinomas. This study
      demonstrates that microsatellites provide a powerful set of DNA markers for loss
      of heterozygosity on archival specimens.

PMID- 8269283
TI  - Detection of trisomy 12 on ovarian sex cord stromal tumors by fluorescence in
      situ hybridization.
AB  - Trisomy of chromosome 12 has been frequently described in various neoplasms,
      particularly in tumors of the female genitourinary tract. Fluorescence in situ
      hybridization with a centromeric repetitive DNA probe, specific for chromosome
      12, was done to detect such cytogenic changes on frozen-tissue sections from 10
      cases of ovarian sex cord stromal tumors. The case series was composed by
      granulosa cell tumors (four cases), fibromas (four cases), thecoma (one case),
      and Sertoli-Leydig cell tumor (one case). In granulosa cell tumors, the range of
      trisomy was 12 to 32% and in fibromas 8 to 22%, whereas in the single case of
      thecoma trisomy was present in 8% and in the Sertoli-Leydig cell tumor in 4% of
      the nuclei examined. These results represent an additional series of cases of
      trisomy 12 in ovarian neoplasms, namely, in ovarian sex cord stromal tumors.

PMID- 8269284
TI  - Detection of the t(14;18) translocation in frozen and formalin-fixed tissue.
AB  - As part of a retrospective study into the prevalence of the t(14;18)
      translocation in B-cell lymphomas, we assessed the suitability of the polymerase
      chain reaction (PCR) to amplify the t(14;18) major breakpoint region (MBR) in
      frozen and formalin-fixed tissue. Considering Southern blotting as a standard,
      the sensitivity of PCR was 81%. Of the various procedures used to extract DNA
      from paraffin-embedded tissue (PET), proteinase K digestion in the presence of
      nonionic detergents gave the highest yield and quality of DNA and the most
      efficient amplification rate. Using this method, excellent amplification rates
      (100%) were obtained for both the beta-globin control sequence and the MBR
      t(14;18) for fixed follicular lymphoma specimens collected in the previous 2 to 6
      years (n = 27). Of nine older PETs, PCR on six gave inconsistent results,
      probably because of the poorer-quality substrate used for amplification.
      Specimens exposed to formol sublimate or formalin-acetic acid-alcohol were as
      suitable for amplification as tissues fixed in neutral-buffered formalin. The
      overall incidence of the MBR t(14;18) in all follicular lymphoma specimens as
      detected by both Southern blotting and PCR was 59% (23 of 39).

PMID- 8269285
TI  - Reentrant circuits and the effects of heptanol in a rabbit model of infarction
      with a uniform anisotropic epicardial border zone.
AB  - INTRODUCTION: The purpose was to study reentry in a rabbit model of infarction.
      METHODS AND RESULTS: A model of an infarct epicardial border zone was produced in
      Langendorff perfused rabbit hearts by freezing the inner two thirds of the left
      ventricular wall, allowing only a thin epicardial muscle layer to survive.
      Reentrant circuits causing stable ventricular tachycardia occurred in the
      surviving rim of epicardial muscle as shown by mapping impulse propagation with a
      196-electrode array. The circuits were functional, and reentry did not occur
      around an anatomical obstacle. Slow conduction in the circuits was caused by the
      anisotropic properties of the epicardial muscle. Activation in the circuits was
      slow transverse to the long axis of the fiber bundles and rapid parallel to the
      long axis. Other features of the circuits, including orientation of the central
      functional line of block parallel to the fiber long axis, and an oval shape are
      also characteristic of anisotropic reentry. Since the slow conduction causing
      reentry is a result of poor transverse intercellular coupling, we determined
      whether the "uncoupler" heptanol would cause block in the circuits and terminate
      tachycardia. Heptanol in concentrations up to 1.2 mM slowed conduction in the
      transverse and longitudinal directions in the circuits and sometimes extended the
      central line of functional block. It did not, however, stop reentry because the
      reentrant impulse was still able to conduct around the ends of the block line.
      CONCLUSION: Drugs that decrease intercellular coupling may not be effective
      antiarrhythmic agents when uniform anisotropy causes functional reentry.

PMID- 8269286
TI  - Alterations in repolarization of cardiac Purkinje fibers recovering from ischemic
      like conditions: genesis of early afterdepolarizations.
AB  - INTRODUCTION: Triggered activity initiated from delayed after-depolarizations has
      been proposed as a possible cause of arrhythmias during reperfusion of ischemic
      myocardium. However, the potential for abnormal repolarization and early
      afterdepolarizations (EADs) to develop under similar conditions has not been
      fully explored. METHODS AND RESULTS: Repolarization of the cell membrane during
      recovery from ischemic-like conditions was analyzed from transmembrane recordings
      in isolated rabbit Purkinje fibers paced at different basic cycle lengths.
      Preparations were exposed to conditions of hypoxia (defined as oxygen tension <
      30 mmHg, high potassium, and zero substrate) plus lactic acidosis (pH 6.7) for 45
      minutes followed by recovery in normal Tyrode's solution. Compared to control,
      action potentials during recovery at basic cycle length of 3,000 msec (n = 11)
      were characterized by a: (1) -7.2 +/- 2.1 mV shift in plateau potential (P <
      0.01); (2) 126.1 +/- 63.6 msec increase in plateau duration (P < 0.05); and (3)
      0.29 +/- 0.07 V/sec slowing of the maximum rate of terminal repolarization (phase
      3; P < 0.01). These changes were larger when 10 to 20 microM amiloride was added
      to the hypoxic, acidotic test solution but were smaller when tissues were
      conditioned with hypoxia alone (zero lactate, pH 7.4). Following hypoxia plus
      acidosis, with or without amiloride, repolarization at long basic cycle lengths
      was often accompanied by EADs predominantly generated from potentials positive to
      -40 mV. These afterpotentials were blocked by Ca2+ channel antagonists and
      exhibited an activation threshold of -26.3 +/- 1.8 mV (n = 7). CONCLUSION: These
      data are consistent with the hypothesis that the combined negative voltage shift
      in the plateau and increase in its duration lead to the genesis of low membrane
      potential EADs by allowing reactivation of Ca2+ channels. Moreover, these results
      suggest that bradycardia-dependent EADs in Purkinje tissue may underlie
      arrhythmias in the intact heart during reperfusion of ischemic myocardium by
      mechanisms that are related in part to the acidosis established during the
      preceding ischemic conditions.

PMID- 8269287
TI  - Spread of excitation in a myocardial volume: simulation studies in a model of
      anisotropic ventricular muscle activated by point stimulation.
AB  - INTRODUCTION: The purpose of this study was to present simulations of excitation
      wavefronts spreading through a parallelepipedal slab of ventricular tissue
      measuring 6.5 x 6.5 x 1.0 cm. METHODS AND RESULTS: The slab incorporates the
      anisotropic properties of the myocardium including the transmural
      counterclockwise fiber rotation from epicardium to endocardium. Simulations were
      based on an eikonal model that determines excitation times throughout the
      ventricular wall, which is represented as an anisotropic bidomain. Excitation was
      initiated by delivering ectopic stimuli at various intramural depths. We also
      investigated the effect of a simplified Purkinje network on excitation patterns.
      Excitation wavefronts in the plane of pacing, parallel to epicardial-endocardial
      surfaces, were oblong with the major axis approximately oriented along the local
      fiber direction, with bulges and deformations due to attraction from rotating
      fibers in adjacent planes. The oblong intersections of the wavefront with planes
      at increasing distance from pacing plane rotated clockwise or counterclockwise,
      depending on pacing depth, but wavefront rotation was always less than fiber
      rotation in the same plane. For all pacing depths, excitation returned toward the
      plane of pacing. Return occurred in multiple, varying sectors of the slab
      depending on pacing depth, and was observed as close as 6 mm to the pacing site.
      CONCLUSION: Curvature of wavefronts and collision with boundaries of slab
      markedly affected local velocities. Shape and separation of epicardial isochrones
      and spatial distribution of epicardial velocities varied as a function of site
      and depth of pacing. When the Purkinje network was added to the model, epicardial
      velocities revealed the subendocardial location of the Purkinje-myocardial
      junctions. Considerable insight into intramural events could be obtained from
      epicardial isochrones. If validated experimentally, results may be applicable to
      epicardial isochrones recorded at surgery.

PMID- 8269288
TI  - The role of free radicals in the pathogenesis of amiodarone toxicity.
AB  - INTRODUCTION: In vitro and in vivo studies were performed to elucidate the
      pathogenesis of amiodarone toxicity. METHODS AND RESULTS: Rats were treated with
      amiodarone alone (500 mg/kg body weight per day) or together with antioxidants
      (silibinin or MTDQ-DA: 50 mg/kg body weight per day) or with either antioxidant
      alone. They received amiodarone for 30 days and antioxidant for 33 days (3 days
      pretreatment). In vitro, amiodarone induced a dose-dependent chemiluminescence
      signal, which was inhibited by the two dihydroquinolin-type antioxidants (MTDQ
      DA, CH 402). Chemiluminometric results from liver homogenate demonstrated that
      simultaneous treatment with silibinin partially prevented the liver homogenate
      superoxide anion radical scavenger capacity decreasing effect of amiodarone.
      Amiodarone treatment caused a significant increase of NADPH and Fe3+ induced
      lipid peroxidation in the liver microsomal fraction, which antioxidants
      (silibinin, MTDQ-DA) were unable to prevent. Light microscopy of the lung tissue
      in amiodarone-treated rats showed accumulation of foamy macrophages with
      thickening of the interalveolar septa, pneumonitis, and variable interstitial
      fibrosis. Antioxidant treatment did not prevent these changes. Electron
      micrographs of lung from amiodarone-treated rats showed lysosomal
      phospholipoidosis, intralysosomal electron dense deposits, and increased lysosome
      number and size. In contrast to rats treated with amiodarone alone, those treated
      with both amiodarone and silibinin had significantly fewer lysosomes (P < 0.01);
      the lysosome size, shape, and internal characteristics remained the same.
      Simultaneous treatment with silibinin and amiodarone decreased lysosomal
      phospholipoidosis compared to amiodarone treatment alone. Simultaneous treatment
      with MTDQ-DA and amiodarone did not show any beneficial effect. Pulse radiolysis
      and cobalt 60-gamma (60Co-gamma) radiolysis studies showed that the main free
      radical product in a reducing environment was a very reactive aryl radical formed
      after the partial deiodination of the amiodarone molecule. The radiosensitizing
      effect of amiodarone was also verified in rat liver microsomal preparations using
      in vivo amiodarone with or without MTDQ-DA pretreatment and 60Co-gamma
      irradiation with or without the in vitro addition of antioxidants (CH 402, MTDQ
      DA). In vivo, the MTDQ-DA treatment also had a radiosensitizing effect; however,
      the in vitro addition of both antioxidants resulted in a radioprotective effect.
      The aryl radical also may emerge in vivo during the metabolism of amiodarone.
      CONCLUSION: These observations suggest that amiodarone in vitro and in vivo
      generates free radicals that may play a role in the pathogenesis of amiodarone
      toxicity beside other well-established mechanisms, and antioxidants may have a
      partial protective effect against amiodarone toxicity.

PMID- 8269289
TI  - Pseudo-pacemaker syndrome following inadvertent fast pathway ablation for
      atrioventricular nodal reentrant tachycardia.
AB  - Atrioventricular nodal reentrant tachycardia that is refractory to drug treatment
      has recently been treated with radiofrequency catheter ablation. In this case
      report we describe a patient with atrioventricular nodal reentrant tachycardia in
      whom radiofrequency ablation of slow pathway was attempted, with inadvertent
      damage to the fast pathway. The patient developed marked first-degree
      atrioventricular block associated with symptoms mimicking pacemaker syndrome.

PMID- 8269290
TI  - Assessment of beat-by-beat control of heart rate by the autonomic nervous system:
      molecular biology technique are necessary, but not sufficient.
AB  - Vagus nerve activity can change heart rate substantially within one cardiac
      cycle, and the chronotropic effects decay almost completely within one cardiac
      cycle after cessation of vagal activity. The ability of the vagus nerves to
      regulate heart rate beat by beat can be explained in large part by the speed at
      which the neural signal is transduced to a cardiac response and by the rapidity
      of the processes that restore the basal heart rate when vagal activity ceases.
      Currently, the question of whether the cardiac cells can transduce the
      sympathetic neural signals rapidly enough to implement beatwise regulation is
      controversial. Emphasis on the speed of the processes that initiate the responses
      may, however, be misplaced. Instead, the processes that terminate the responses
      to autonomic neural activity (especially those processes that remove the released
      neurotransmitters) are probably the main determinants of the ability of the vagal
      and sympathetic systems to affect beatwise control. The norepinephrine (NE)
      released from the sympathetic nerve endings is removed from the cardiac tissues
      much more slowly than is the acetylcholine that is released from the vagal
      terminals. As a consequence of the potential deleterious effects associated with
      the slow removal of NE, the cardiac neural control system has evolved such that
      the sympathetic nerves ordinarily release NE at a slow rate. Hence, changes in
      sympathetic neural activity can alter cardiac behavior only slightly from beat to
      beat. Hence, beatwise control of cardiac function would be negligible, regardless
      of how swiftly the sympathetic nerve impulse is transduced to a change in cardiac
      performance.

PMID- 8269291
TI  - Radiofrequency current catheter ablation for control of supraventricular
      arrhythmias.
AB  - With the advent of radiofrequency energy, catheter ablation techniques have
      become an accepted form of treatment for a variety of supraventricular
      arrhythmias. The ablation of the atrioventricular (AV) node was performed first
      and is now widely used in patients with refractory atrial fibrillation or
      flutter. Ablation has also replaced surgery in patients with preexcitation
      syndromes, and as the complication rate in experienced centers is low, it has
      become the first line of treatment in these institutions. The results of catheter
      ablation in AV nodal reentrant tachycardia are excellent as well, although there
      is still debate about whether "slow" pathway ablation is superior to "fast"
      pathway ablation. Radiofrequency current ablation has also contributed to a
      better understanding of the pathophysiology of AV nodal reentrant tachycardia, as
      it has provided evidence for atrial participation in the reentrant circuit.
      Experience with atrial tachycardias and tachycardias due to Mahaim fibers remains
      limited. The ideal source of energy for specific arrhythmias is still unknown and
      improvement in catheter technology is needed.

PMID- 8269292
TI  - Drug therapy for torsade de pointes.
AB  - Torsade de pointes is an uncommon and unique type of ventricular tachycardia. It
      differs from other forms of ventricular tachycardia by its morphological
      features, underlying mechanism, and modes of therapy. Recognizing torsade de
      pointes is of major clinical importance, as standard antiarrhythmic regimens
      might not only be ineffective in abolishing this life-threatening arrhythmia but
      may aggravate it. Torsade de pointes is most commonly precipitated by QT
      prolonging drugs, mainly type IA antiarrhythmic therapy such as quinidine and
      disopyramide, and other antiarrhythmic agents are reported to cause torsade de
      pointes as well. Predisposing factors known to increase the likelihood of
      developing torsade de pointes are: electrolyte imbalance (hypokalemia,
      hypomagnesemia, or both) and slow heart rate induced either by sinus bradycardia
      or heart block. Treatment of torsade de pointes is aimed at shortening the QT
      interval. By acceleration of the heart rate, the QT interval is shortened, thus
      preventing the recurrence of the arrhythmia. Treatment of torsade de pointes
      includes: isoproterenol infusion, cardiac pacing, and intravenous atropine.
      Intravenous magnesium sulfate, a relatively new mode of therapy for torsade de
      pointes, was proven to be extremely effective and is now regarded as the
      treatment of choice for this arrhythmia.

PMID- 8269293
TI  - Implantable cardioverter defibrillator: Ventritex Cadence.
AB  - The Ventritex Cadence Model V-100 Tiered Therapy Defibrillator is a third
      generation antitachyarrhythmia device currently completing clinical trials in the
      United States. The implantable pulse generator is capable of high energy
      defibrillation, low energy cardioversion, as well as antitachycardia and
      bradycardia pacing. In addition, this microprocessor controlled device can
      deliver monophasic or biphasic defibrillation/cardioversion shocks, is
      noncommitted to deliver shock therapy after initiating charging for
      defibrillation or cardioversion therapy, and can store electrograms of
      spontaneous tachyarrhythmia episodes. These expanded device capabilities should
      improve therapy efficacy and patient management, and represent a major advance in
      the treatment of patients with ventricular tachyarrhythmias.

PMID- 8269294
TI  - Complexities of junctional tachycardias.
AB  - The atrioventricular junction is a compact area in which most of the known
      electrophysiologic substrates and mechanisms play a role in the genesis and
      maintenance of tachyarrhythmias. The purpose of this review is to summarize the
      data on normal atrioventricular junction anatomy and electrophysiologic function
      and correlate that information with surface electrocardiographic recordings,
      intracardiac electrophysiologic data, and interventional data from surgical and
      catheter techniques. Models of tachycardia mechanisms are proposed for typical
      and atypical atrioventricular nodal reentrant tachycardia, permanent junctional
      reciprocating tachycardia, and orthodromic supraventricular tachycardias
      utilizing "intermediate septal" accessory connections.

PMID- 8269295
TI  - Electrophysiologic spectrum of atrioventricular nodal behavior in patients with
      atrioventricular nodal reentrant tachycardia undergoing selective fast or slow
      pathway ablation.
AB  - INTRODUCTION: The objective of this report is to delineate the atrioventricular
      (AV) nodal electrophysiologic behavior in patients undergoing fast or slow
      pathway ablation for control of their AV nodal reentrant tachycardia (AVNRT).
      METHODS AND RESULTS: One hundred sixteen consecutive patients with symptomatic
      AVNRT were included. Twenty-two patients underwent fast pathway ablation with
      complete abolition of AVNRT in all and development of complete AV block in five
      patients. Of 17 patients with intact AV conduction postablation, 12 had
      demonstrated antegrade dual pathway physiology during baseline study, which was
      maintained in three and lost in nine patients postablation. Two patients with
      successful fast pathway ablation developed uncommon AVNRT necessitating a slow
      pathway ablation. Twenty-one patients demonstrated both common and uncommon forms
      of AV nodal reentry during baseline study. The earliest site of atrial activation
      was close to the His-bundle recording site (anterior interatrial septum) during
      common variety and the coronary sinus ostium (posterior interatrial septum)
      during the uncommon AV nodal reentry in all 21 patients. Ninety-six patients
      underwent successful slow pathway ablation. Among these, the antegrade dual
      pathway physiology demonstrable during baseline study (60 patients) was
      maintained in 25 and lost in 35 patients postablation. CONCLUSION: These data
      suggest that: (1) dual pathway physiology may persist after successful ablation,
      which might be a reflection of multiple reentrant pathways in patients with
      AVNRT; and (2) the retrograde pathways during common and uncommon AVNRT have
      anatomically separate atrial breakthroughs. These findings have important
      electrophysiologic implications regarding the prevailing concept of the AV nodal
      physiology in patients with AVNRT.

PMID- 8269296
TI  - The response of paroxysmal supraventricular tachycardia to overdrive atrial and
      ventricular pacing: can it help determine the tachycardia mechanism?
AB  - INTRODUCTION: Standard electrophysiologic techniques generally allow
      discrimination among mechanisms of paroxysmal supraventricular tachycardia. The
      purpose of this study was to determine whether the response of paroxysmal
      supraventricular tachycardia to atrial and ventricular overdrive pacing can help
      determine the tachycardia mechanism. METHODS AND RESULTS: Fifty-three patients
      with paroxysmal supraventricular tachycardia were studied. Twenty-two patients
      had the typical form of atrioventricular (AV) junctional (nodal) reentry, 18
      patients had orthodromic AV reentrant tachycardia, 10 patients had atrial
      tachycardia, and 3 patients had the atypical form of AV nodal reentrant
      tachycardia. After paroxysmal supraventricular tachycardia was induced, 15-beat
      trains were introduced in the high right atrium and right ventricular apex
      sequentially with cycle lengths beginning 10 msec shorter than the spontaneous
      tachycardia cycle length. The pacing cycle length was shortened in successive
      trains until a cycle of 200 msec was reached or until tachycardia was terminated.
      Several responses of paroxysmal supraventricular tachycardia to overdrive pacing
      were useful in distinguishing atrial tachycardia from other mechanisms of
      paroxysmal supraventricular tachycardia. During decremental atrial overdrive
      pacing, the curve relating the pacing cycle length to the VA interval on the
      first beat following the cessation of atrial pacing was flat or upsloping in
      patients with AV junctional reentry or AV reentrant tachycardia, but variable in
      patients with atrial tachycardia. AV reentry and AV junctional reentry could
      always be terminated by overdrive ventricular pacing whereas atrial tachycardia
      was terminated in only one of ten patients (P < 0.001). The curve relating the
      ventricular pacing cycle length to the VA interval on the first postpacing beat
      was flat or upsloping in patients with AV junctional reentry and AV reentry, but
      variable in patients with atrial tachycardia. The typical form of AV junctional
      reentry could occasionally be distinguished from other forms of paroxysmal
      supraventricular tachycardia by the shortening of the AH interval following
      tachycardia termination during constant rate atrial pacing. CONCLUSIONS: Atrial
      and ventricular overdrive pacing can rapidly and reliably distinguish atrial
      tachycardia from other mechanisms of paroxysmal supraventricular tachycardia and
      occasionally assist in the diagnosis of other tachycardia mechanisms. In
      particular, the ability to exclude atrial tachycardia as a potential mechanism
      for paroxysmal supraventricular tachycardia has important implications for the
      use of catheter ablation techniques to cure paroxysmal supraventricular
      tachycardia.

PMID- 8269297
TI  - Bundle branch reentrant ventricular tachycardia: cumulative experience in 48
      patients.
AB  - INTRODUCTION: The clinical, electrophysiologic features and follow-up of 48
      patients with inducible bundle branch reentrant (BBR) tachycardia are presented.
      METHODS AND RESULTS: Forty-eight patients were identified in whom a diagnosis of
      BBR tachycardia was made during electrophysiologic evaluation. The clinical
      presentation was syncope or sudden death in 38 patients, and sustained
      palpitations during wide QRS complex tachycardia in 5 patients.
      Electrophysiologic studies were performed in 5 additional patients for various
      other reasons. Structural heart disease was present in 45 patients. Idiopathic
      dilated cardiomyopathy and coronary artery disease were the anatomical substrates
      in 19 (39%) and 24 (50%) patients, respectively, severe aortic regurgitation was
      present in 2 patients, and no organic heart disease was identified in 3. All 48
      patients had evidence of His-Purkinje system disease. BBR tachycardia with left
      and right bundle branch block morphologies was induced in 46 and 5 patients,
      respectively, and interfascicular BBR tachycardia was initiated in 2 patients.
      Ventricular tachycardia of a myocardial origin was induced in 11 patients.
      Management of BBR tachycardia included transcatheter bundle branch ablation in 28
      patients, and antiarrhythmic drug therapy in 16 patients. Four patients were
      treated with implantable defibrillators. After a mean follow-up of 15.8 months in
      42 patients, there were 13 deaths due to congestive heart failure, 4 sudden
      cardiac deaths, 3 nonsudden cardiac deaths, and 3 noncardiac related deaths.
      CONCLUSION: Sustained BBR, a form of monomorphic ventricular tachycardia, is a
      highly malignant arrhythmia usually seen in patients with structural heart
      disease. Three different types of BBR tachycardia are described. If distinguished
      from ventricular tachycardia of a myocardial origin, catheter ablation of the
      right bundle branch can be easily performed and effectively eliminates BBR.
      During follow-up, congestive heart failure is the most common cause of death in
      this population.

PMID- 8269298
TI  - Bundle branch reentrant tachycardia: a chance to cure?

PMID- 8269299
TI  - Activation mapping of reentry around an anatomical barrier in the canine atrium:
      observations during the action of the class III agent, d-sotalol.
AB  - INTRODUCTION: In the chronically instrumented animal and the isolated blood
      perfused heart, atrial reentry via a fixed path around an anatomical obstacle has
      been described and is terminated by the Class III antiarrhythmic agent, d
      sotalol. The precise mechanism by which d-sotalol terminates this arrhythmia is
      not known. METHODS AND RESULTS: In the present study, right atrial (RA)
      activation sequences in the isolated, coronary artery perfused canine heart
      during episodes of sustained flutter (n = 7) and drug administration were
      determined. A fixed array of bipolar electrodes was used to record endocardial
      electrograms from 96 sites on the RA simultaneously. Maps of all control flutters
      showed that the rhythm was due to persistent circus movement of the impulse
      around the tricuspid valve ring. D-sotalol was effective in terminating atrial
      reentry in this model. In all episodes, block of the excitatory impulse in a
      specific region of the reentrant circuit accompanied these terminations. However,
      the events preceding the occurrence of block of the impulse were not similar. Two
      different modes of termination are described. CONCLUSION: The Class III
      antiarrhythmic agent d-sotalol can terminate atrial reentry in several ways. In
      one mode, complete conduction block of the reentering impulse within the fixed
      path occurs to terminate the rhythm. In the other mode, interruption of the
      original reentrant circuit occurs when there is failure of a lateral boundary.
      Often in this latter case, interruption of the original circuit is by an extra
      impulse that is secondary to a change in the path of the impulse. In both modes
      cycle length oscillations are observed.

PMID- 8269300
TI  - Retrograde (transseptal) activation of right bundle branch during sinus rhythm.
AB  - A 40-year-old man undergoing electrophysiologic study for recurrent palpitations
      was found to have a right bundle branch block during sinus rhythm and right
      bundle potentials occurring after ventricular activation. The sequence of
      activation of the proximal and distal right bundle potentials was suggestive of a
      retrograde invasion of the right bundle during sinus rhythm. This transseptal
      activation of the right bundle via the left bundle exhibited decremental
      conduction characteristics during atrial as well as ventricular stimulation.
      Observations made in this case may provide some important information concerning
      the electrophysiologic behavior of transseptal impulses.

PMID- 8269301
TI  - Recent insights pertaining to sarcolemmal phospholipid alterations underlying
      arrhythmogenesis in the ischemic heart.
AB  - Myocardial ischemia in vivo is associated with dramatic electrophysiologic
      alterations that occur within minutes of cessation of coronary flow and are
      rapidly reversible with reperfusion. This suggests that subtle and reversible
      biochemical alterations within or near the sarcolemma may contribute to the
      electrophysiologic derangements. Our studies have concentrated on two amphipathic
      metabolites, long-chain acylcarnitines and lysophosphatidylcholine (LPC), which
      have been shown to increase rapidly in ischemic tissue in vivo and to elicit
      electrophysiologic derangements in normoxic tissue in vitro. Incorporation of
      these amphiphiles into the sarcolemma at concentrations of 1 to 2 mole%, elicits
      profound electrophysiologic derangements analogous to those observed in ischemic
      myocardium in vivo. The pathophysiological effects of the accumulation of these
      amphiphiles are thought to be mediated by alterations in the biophysical
      properties of the sarcolemmal membrane, although there is a possibility of a
      direct effect upon ion channels. Inhibition of carnitine acyltransferase I (CAT
      I) in the ischemic cat heart was found to prevent the increase in long-chain
      acylcarnitines and LPC and to significantly reduce the incidence of malignant
      arrhythmias including ventricular tachycardia and fibrillation. This review
      focuses on the electrophysiologic derangements that are observed during early
      ischemia and presents data supporting the concept that accumulation of these
      amphiphiles within the sarcolemma contributes to these changes. The potential
      contribution of these amphiphiles to the increases in extracellular potassium and
      intracellular calcium are examined. Finally, recent data pertaining to the
      accumulation of long-chain acylcarnitines on cell-to-cell uncoupling are
      presented. In addition to the events reviewed here, there are many other
      alterations that occur during early myocardial ischemia, but the results from
      multiple studies over the past two decades indicate that the accumulation of
      these amphiphiles contributes importantly to arrhythmogenesis and that
      development of specific inhibitors of CAT-I or phospholipase A2 may be a
      promising therapeutic strategy to attenuate the incidence of lethal arrhythmias
      associated with ischemic heart disease in man.

PMID- 8269302
TI  - Aggravation of arrhythmia: a complication of antiarrhythmic drugs.
AB  - Aggravation of arrhythmia, defined as worsening of a preexisting arrhythmia or
      the occurrence of a new arrhythmia, is a common complication of antiarrhythmic
      drug therapy. Although it is largely an unpredictable event, patients at greatest
      risk are those with a history of congestive heart failure due to systolic
      dysfunction who present with a sustained ventricular tachyarrhythmia. As a rule,
      aggravation of arrhythmia is an early event, occurring within the first few days
      of initiating therapy. However, in the Cardiac Arrhythmia Suppression Trial
      (CAST), the increased sudden death mortality due to drug therapy, which was a
      result of arrhythmia aggravation, occurred throughout the entire duration of the
      trial, suggesting that arrhythmia aggravation can also be a late complication of
      therapy. Also disturbing was the fact that patients in CAST were low risk and did
      not have congestive heart failure or a serious ventricular tachyarrhythmia. This
      suggests that another important risk factor is myocardial ischemia and its
      potentially dangerous interaction with antiarrhythmic drugs. In patients with
      heart disease, especially those with coronary artery disease, antiarrhythmic
      drugs must therefore be used cautiously. Close and continuous follow-up is
      mandatory.

PMID- 8269303
TI  - "Supernormal" conduction and excitability.
AB  - Electrocardiographic manifestation of "supernormal" conduction is defined as
      conduction that is more rapid than expected or presence of conduction when block
      is anticipated. It is not supernormal in the sense or being more rapid than
      normal. Therefore, the term relative supernormality or "supernormality" is more
      appropriate. The mechanism of "supernormal" conduction is conduction during a
      period of supernormal excitability and conduction associated with altered
      membrane potential. Some of the more common phenomena that are not dependent on
      conduction during the supernormal period but manifest better than expected
      conduction, thus simulating "supernormal" conduction, include dual AV nodal
      conduction, the "gap" phenomenon, "peeling back" of the refractory period,
      summation of subthreshold responses, diastolic phase 4 depolarization, and phasic
      autonomic influences.

PMID- 8269304
TI  - Cardiac arrhythmias and the autonomic nervous system.
AB  - The multiple facets of cardiac arrhythmias and their relationship with the
      autonomic nervous system can be investigated by studying the spontaneous heart
      rate behavior through ambulatory ECG recordings, an approach that complements the
      limitations of invasive electrophysiologic investigations. Information obtained
      from heart rate behavior is more reliable in the absence of structural heart
      disease and ventricular hypertrophy/failure, during which compensatory mechanisms
      involving the autonomic nervous system tend to limit reflex changes in heart
      rate. Thus, in such situations, less marked sinus rhythm variations preceding the
      arrhythmia onset do not imply a more limited influence of the autonomic nervous
      system, and the sensitivity of the electrophysiologic substrate may otherwise
      vary. These two factors may combine to form the basis of the "adrenergic paradox"
      that implies that the more marked the autonomic nervous system dependence of
      tachyarrhythmias, the less obvious its evidence. Assessment of the QT interval
      dynamicity may also allow one to evaluate the modulation of autonomic neural
      effects on the ventricular tissues. Finally, it may be difficult to distinguish
      clearly autonomic nervous system dependence from rate dependence: the latter
      frequently conditions the behavior of the trigger whereas the former mainly
      concerns the electrophysiologic substrate. There are many examples of the
      importance of the autonomic nervous system as a determinant of cardiac
      arrhythmias. In the atrium, either limb of the autonomic nervous system,
      particularly the parasympathetic limb, can generate atrial fibrillation. The
      absence of structural heart disease defines pure electrophysiologic substrates
      responsible for benign forms of ventricular tachycardia as well as potentially
      lethal tachyarrhythmias of the long QT syndrome and its variants. In both, the
      role of the autonomic nervous system is essential, although the therapeutic
      consequences are crucial only in the latter. In the presence of heart disease
      and, in particular, heart failure, the autonomic nervous system behavior is more
      difficult to assess than in the absence of structural heart disease. This does
      not mean that its role is less crucial. In this situation the beneficial effects
      of beta blockers may be as important as in normal hearts although physicians
      should be more cautious when heart failure is present.

PMID- 8269305
TI  - Idiopathic ventricular tachycardia and fibrillation.
AB  - Important data have recently been added to our understanding of sustained
      ventricular tachyarrhythmias occurring in the absence of demonstrable heart
      disease. Idiopathic ventricular tachycardia (VT) is usually of monomorphic
      configuration and can be classified according to its site of origin as either
      right monomorphic (70% of all idiopathic VTs) or left monomorphic VT. Several
      physiopathological types of monomorphic VT can be presently individualized,
      according to their mode of presentation, their relationship to adrenergic stress,
      or their response to various drugs. The long-term prognosis is usually good.
      Idiopathic polymorphic VT is a much rarer type of arrhythmia with a less
      favorable prognosis. Idiopathic ventricular fibrillation may represent an
      underestimated cause of sudden cardiac death in ostensibly healty patients. A
      high incidence of inducibility of sustained polymorphic VT with programmed
      ventricular stimulation has been found by our group, but not by others. Long-term
      prognosis on Class IA antiarrhythmic medications that are highly effective at
      electrophysiologic study appears excellent.

PMID- 8269306
TI  - Role of radiofrequency ablation in the management of supraventricular
      arrhythmias: experience in 760 consecutive patients.
AB  - INTRODUCTION: Several reports have demonstrated that radiofrequency catheter
      ablation provides effective control of a variety of supraventricular
      tachycardias. However, the efficacy, complications, risk of arrhythmia
      recurrence, and follow-up survival analysis have not been reported in a large
      series of consecutive patients with supraventricular arrhythmias with diverse
      electrophysiologic mechanisms. This report details the results of radiofrequency
      catheter ablation in 760 consecutive patients (386 males, 374 females) with a
      wide variety of supraventricular tachycardias treated at one center. METHODS AND
      RESULTS: Arrhythmias were associated with the presence of an accessory pathway in
      363 patients (384 accessory pathways), including four patients with Mahaim fibers
      and eight patients with the permanent form of junctional reciprocating
      tachycardia. The mechanism of the clinical arrhythmia was AV nodal reentrant
      tachycardia in 245 patients, and a primary atrial tachycardia in 20 patients
      (ectopic atrial tachycardia in 16 patients and sinus nodal reentry in 4
      patients). Ablation of the reentrant circuit of atrial flutter within the right
      atrium was attempted in 13 patients. AV node ablation and permanent pacemaker
      implantation were performed in 119 patients with medically refractory atrial
      fibrillation or flutter. Radiofrequency catheter ablation was successful in 346
      of 363 patients (95.3%, CI 93.1%-97.5%) with accessory pathways (367 of 384
      pathways, 95.6%, CI 93.5%-97.6%) with a complication rate of 1.1% and a
      recurrence rate of 5.5%. Successful accessory pathway ablation was achieved for
      179 of the first 192 pathways treated (93.2%, CI 89.7%-96.6%) and increased to
      188 of 192 pathways (97.9%, CI 95.9%-99.9%) over the second half of the series.
      AV nodal reentry was successfully abolished in 244 of 245 patients (99.6%, CI
      98.8%-100%) by selective ablation of the slow pathway in 234 patients and the
      fast pathway in 10 patients. The complication rate in this group was 2.0% with a
      recurrence rate of 6.5%. All 20 primary atrial tachycardias were successfully
      ablated with no complications and a recurrence rate of 15%. The reentrant circuit
      of atrial flutter was ablated successfully in 10 of 13 patients (77%) with
      recurrent atrial flutter in one additional patient. Complete AV block was
      achieved in 117 of 119 (98.3%, CI 96.0%-100%) patients with atrial fibrillation
      or flutter treated by AV nodal ablation with a complication rate of 0.8% and
      recurrence of AV conduction in 6%. The median duration of fluoroscopy exposure
      for the population was 23.4 minutes. The overall primary success rate for the
      entire population was 97.0% (737 of 760 patients, CI 95.8%-98.2%). CONCLUSION:
      Thus, the results of this large series of patients demonstrates the safety and
      efficacy of radiofrequency ablation for the treatment of a wide variety of
      supraventricular arrhythmias. It also appears that increasing experience with
      these procedures increases the rate of successful ablation and decreases the risk
      of complications.

PMID- 8269307
TI  - Radiofrequency catheter ablation for supraventricular tachycardias: blazing paths
      or burning bridges?

PMID- 8269308
TI  - Effects of overdrive stimulation on functional reentrant circuits causing
      ventricular tachycardia in the canine heart: mechanisms for resumption or
      alteration of tachycardia.
AB  - INTRODUCTION: The purpose of the experiments described in this article was to
      investigate the effects of overdrive stimulation on functional anisotropic
      reentrant circuits causing ventricular tachycardia in infarcted canine
      ventricles. We determined how overdrive stimuli affect reentrant circuits to
      alter characteristics of the tachycardia. METHODS AND RESULTS: Activation
      patterns were determined by mapping excitation with a 192 bipolar electrode
      array. We found that overdrive stimuli could activate the circuits with the same
      pattern as the reentrant wavefront and that after overdrive stopped either the
      last or the next to last stimulated wavefront continued propagating through the
      circuit as a new reentrant impulse and tachycardia continued. When the circuit
      was not altered after overdrive, the exit route that the stimulated wavefront
      took from the circuit to activate the rest of the ventricles was also not altered
      and the tachycardia after overdrive had the same cycle length and QRS morphology
      as prior to overdrive. In some experiments, however, the overdrive stimuli did
      not follow the original reentrant pathway but led to the formation of a different
      circuit with a different exit route to the ventricles. As a result, after
      overdrive stimulation tachycardia had a different QRS morphology and cycle length
      than prior to stimulation. When the new circuit after overdrive was small and the
      revolution time of the reentrant impulse around the circuit was short,
      fibrillation occurred. CONCLUSION: Functional reentrant circuits can either be
      maintained or altered after a period of overdrive stimulation. The results
      explain many of the effects that have been seen during overdrive stimulation of
      clinical ventricular tachycardia.

PMID- 8269309
TI  - Generation of reentry in anisotropic myocardium.
AB  - INTRODUCTION: We investigated numerically the effects of the rotation of fiber
      axis orientation through the myocardial wall on wave propagation. METHODS AND
      RESULTS: We show that because of this rotation and inherent discrete properties
      of myocardium, a premature stimulus can create unidirectional conduction block
      leading to reentry. CONCLUSION: The dynamics of the subsequent reentrant patterns
      are complicated by the presence of rotational anisotropy, as the center of
      reentry drifts, and the reentry terminates in finite time when it collides with
      the domain boundary.

PMID- 8269310
TI  - Calcium current in single human cardiac myocytes.
AB  - INTRODUCTION: Significant species-, tissue-, and age-dependent differences have
      been described for the L-type calcium current (ICa). Therefore, extrapolation of
      data obtained from the many animal models to human cardiac physiology is
      difficult. In this study, we have characterized the voltage-dependent properties
      of ICa from pediatric and adult, atrial and ventricular human heart tissue.
      METHODS AND RESULTS: ICa was measured in single human heart muscle cells using
      the "whole cell," voltage clamp method. Single myocytes were isolated from
      myocardial specimens obtained intraoperatively from both pediatric and adult
      patients (ages 3 months to 75 years) undergoing cardiac surgery. Cells obtained
      for these experiments appeared to be healthy; the resting potential was between 
      80 and -85 mV. The action potential shape and duration and current-voltage
      relationship for ICa were similar to that reported by others for human heart
      cells. The steady-state activation variable, d infinity, was found to be similar
      in both pediatric atrial and ventricular cells but shifted approximately 5 mV
      negative in the adult atrial and ventricular cells. ICa of all cells displayed
      biexponential inactivation and steady-state inactivation was incomplete at
      positive potentials (steady-state inactivation curves turned up at positive
      potentials) consistent with inactivation arising from voltage-dependent and
      calcium-dependent processes as reported in heart cells from many species. The
      potential of maximal inactivation was more negative for adult cells (around -10
      mV) than pediatric cells (around 0 mV). Estimates of the calcium "window"
      current, using a modified Hodgkin-Huxley model, could explain measured
      differences in action potential shape and duration. CONCLUSION: Human cardiac ICa
      can be investigated using whole cell, voltage clamp methods and a modified
      Hodgkin-Huxley model. Quantitative characterization of many of the properties of
      ICa in human heart tissue suggests that important species differences do exist
      and that further investigations are required to characterize the dependence of
      inactivation on [Ca2+]i in human heart cells. Since the array of characteristics
      of ICa in different species varies, the study of human myocardial cells per se
      continues to be important when examining human cardiac physiology.

PMID- 8269311
TI  - Potential distributions generated by point stimulation in a myocardial volume:
      simulation studies in a model of anisotropic ventricular muscle.
AB  - INTRODUCTION: We present simulations of extracellular potential patterns elicited
      by delivering ectopic stimuli to a parallelepipedal slab of ventricular tissue
      represented as an anisotropic bidomain incorporating epi-endocardial fiber
      rotation. METHODS AND RESULTS: Simulations were based on an eikonal model that
      determines wavefront shapes throughout the slab at every time instant during the
      depolarization phase, coupled with an approximate model of the action potential
      profile. The endocardial face of the slab was in contact with blood and the
      composite volume was surrounded by an insulating medium. The effect of a
      simplified Purkinje network was also studied. RESULTS: (1) For all pacing depths,
      except endocardial pacing, a central negative area and two potential maxima were
      observed at QRS onset in all intramural planes parallel to the epicardium. In all
      planes, the axis joining the two maxima was approximately aligned with the
      direction of fibers in the plane of pacing. Endocardial pacing generated a
      different pattern, but only when blood was present; (2) During later stages of
      excitation, outflowing currents (from the wavefront toward the resting tissue)
      were always emitted, at all intramural depths, only from those portions of the
      wavefront that spread along fibers. At any given instant, the position of the two
      potential maxima in a series of planes parallel to the epicardium and
      intersecting the wavefront rotated as a function of depth, following the rotating
      direction of intramural fibers. Purkinje involvement modified the above patterns.
      CONCLUSION: Epicardial and endocardial potential maps provided information on
      pacing site and depth and on subsequent intramural propagation by reflecting the
      clockwise or counter-clockwise rotation of the deep positivity. Results may be
      applicable to epicardial and endocardial potential maps recorded at surgery or
      from endocavitary probes.

PMID- 8269312
TI  - Sequential bilateral bundle branch block during dofetilide, a new class III
      antiarrhythmic agent, in a patient with atrial fibrillation.
AB  - INTRODUCTION: The mechanism of wide QRS complex tachycardias during dofetilide
      infusion was studied in a patient with atrial fibrillation. METHODS AND RESULTS:
      Endocardial recordings from the intraventricular conduction system showed that
      dofetilide caused "classic" aberrant conduction (Ashman phenomenon, typical QRS
      morphology) at high prematurity ratios (preceding interval = 1.78 x coupling
      interval--290), thus mimicking ventricular ectopy. In addition, there was
      frequent sequential bilateral bundle branch block, caused by a significant
      difference in preceding bundle-to-bundle intervals (mean difference +/- 1 SD: 74
      +/- 26 msec). CONCLUSION: The present findings may prove helpful in the clinical
      assessment of wide QRS complex rhythms after dofetilide and possibly other "pure"
      Class III antiarrhythmics.

PMID- 8269313
TI  - Unexpected emergence of manifest preexcitation following transcatheter ablation
      of concealed accessory pathways.
AB  - INTRODUCTION: The basis for anterograde or retrograde unidirectional block of
      accessory pathways still remains a controversial issue. METHODS AND RESULTS: Four
      of 19 consecutive patients (1 male, 3 female; ages 27 to 34 years) who underwent
      transcatheter ablation of concealed accessory pathways developed manifest
      preexcitation after the ablation. The location of the concealed accessory
      pathways in these four patients were right lateral, left posteroseptal, left
      posterolateral, and left lateral. Radiofrequency current was used in three of the
      four patients and high energy direct current in one patient. After ablation,
      manifest preexcitation was observed in these four patients for the first time.
      Manifest preexcitation developed immediately after ablation in two of the four
      patients and after 4 and 14 days in the other two. Detailed endocardial mapping
      revealed that the manifest preexcitation originated from the same location as the
      concealed pathways. Subsequently, catheter ablation was successfully performed in
      three of the four patients using radiofrequency current. One patient underwent
      successful surgical ablation. No recurrence of preexcitation was observed during
      a follow-up period of 9 to 38 months. All patients remained free of arrhythmias.
      CONCLUSION: The basis for this unexpected emergence of preexcitation in these
      patients with only retrograde conducting accessory pathways deserves further
      investigation. Although not compared in the present study, this phenomenon has
      not been reported in patients who underwent surgical interruption of accessory
      pathways. We postulate that a lesion at the site of insertion of the accessory
      pathway had modified the anterograde conduction capacity.

PMID- 8269314
TI  - Spontaneous myocardial calcium oscillations: are they linked to ventricular
      fibrillation?
AB  - The physiological oscillation of cytosolic [Ca2+] that underlies each heart beat
      is generated by the sarcoplasmic reticulum (SR) in response to an action
      potential (AP) and occurs relatively synchronously within and among cells. When
      the myocardial cell and SR Ca2+ loading become sufficiently high, the SR can also
      generate spontaneous, i.e., not triggered by sarcolemmal depolarization, Ca2+
      oscillations (S-CaOs). The purpose of this review is to describe properties of S
      CaOs in individual cells, myocardial tissue, and the intact heart, and to examine
      the evidence that may link S-CaOs to the initiation or maintenance of ventricular
      fibrillation (VF). The SR Ca2+ release that generates S-CaOs occurs locally
      within cells and spreads within the cell via Ca(2+)-induced Ca2+ release. The
      localized increase in cytosolic [Ca2+] due to S-CaOs may equal that induced by an
      AP and causes oscillatory sarcolemmal depolarizations of cells in which it
      occurs. These oscillatory depolarizations are due to Ca2+ activation of the Na/Ca
      exchanger and of nonspecific cation channels. Asynchronous occurrence of
      diastolic S-CaOs among cells within the myocardium causes inhomogeneity of
      diastolic SR Ca2+ loading; this leads to inhomogeneity of the systolic cytosolic
      [Ca2+] transient levels in response to a subsequent AP, which leads to
      heterogeneity of AP repolarization, due to heterogeneous Ca2+ modulation of the
      Na/Ca exchanger, nonspecific cation channels, and of the L-type Ca2+ channel. In
      a tissue in which asynchronous S-CaOs are occurring in diastole, the subsequent
      AP temporarily synchronizes SR Ca2+ loading and release within and among cells.
      Varying extents of synchronized S-CaOs then begin to occur during the subsequent
      diastole. The partial synchronization of this diastolic S-CaOs among cells within
      myocardial tissue produces aftercontractions and diastolic depolarizations. When
      S-CaOs are sufficiently synchronized, the resultant depolarizations summate and
      can be sufficient to trigger a spontaneous AP.S-CaOs occurrence within some cells
      during a long AP plateau also modulates the removal of voltage inactivation of L
      type Ca2+ channels and increases the likelihood for "early afterdepolarizations"
      to occur in myocardial tissue. S-CaOs have an apparent modulatory role in the
      initiation of VF in the Ca2+ overload model and in the reflow period following
      ischemia. Likewise, in non-a priori Ca2+ overloaded hearts, S-CaOs modulate the
      threshold for VF induction (induced typically by alternating current) but may not
      be essential for VF induction.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8269315
TI  - The clinical significance of nonsustained ventricular tachycardia.
AB  - Nonsustained ventricular tachycardia (NSVT) is an arrhythmia not often associated
      with symptoms; however, its occurrence in patients with structural heart disease
      is a prognostic indicator of an increased risk of mortality and sudden death. The
      management of asymptomatic patients with NSVT should first attempt to identify
      which patients are at highest risk for cardiac arrest, and second, devise a
      treatment that can reduce the incidence and/or mortality of cardiac arrest in
      this group. In patients with chronic coronary artery disease (CAD) and NSVT,
      programmed electrical stimulation identifies both a low and high risk group with
      respect to occurrence of ventricular arrhythmias. The negative predictive value
      of programmed electrical stimulation in patients with CAD and NSVT has been well
      established; however, uncertainty remains as to the optimal therapy for CAD
      patients with inducible ventricular arrhythmias. A number of reports suggest that
      patients whose inducible ventricular arrhythmias are rendered noninducible with
      antiarrhythmic drugs have a much lower risk of sudden death. It is yet to be
      resolved whether arrhythmias rendered noninducible identify a subgroup at low
      risk for cardiac arrest, independent of treatment. There is some evidence to
      suggest that the frequency of NSVT in patients with nonischemic dilated
      cardiomyopathy identifies a group at higher risk of sudden death. Programmed
      electrical stimulation adds little in helping to identify which of these patients
      are most likely to have cardiac arrest. The presence of NSVT in asymptomatic
      patients with hypertrophic cardiomyopathy may identify a group at higher risk for
      cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269316
TI  - Inducibility of atrial fibrillation before and after radiofrequency catheter
      ablation of accessory atrioventricular connections.
AB  - INTRODUCTION: The purpose of this study was to evaluate the inducibility of
      atrial fibrillation in patients with an accessory atrioventricular connection
      (AAVC) and to determine if the inducibility of atrial fibrillation is altered
      after successful radiofrequency catheter ablation of the AAVC. METHODS AND
      RESULTS: Thirty-seven patients with an AAVC and 36 control patients were
      prospectively evaluated using a standardized atrial pacing protocol. The high
      right atrium was paced using a 25-beat drive train, 1.5-second intertrain pause,
      10-mA pulse amplitude, and 2-msec pulse duration at cycle lengths of 250 to 100
      msec, in 10-msec decrements. Pacing was performed twice at each cycle length.
      Thirty patients with an AAVC underwent repeat atrial overdrive pacing after
      successful radiofrequency ablation of the AAVC. Atrial fibrillation was induced
      in 26 (70%) patients with an AAVC and 22 (61%) controls (P = NS). Atrial flutter
      was induced in 11 (30%) patients with an AAVC and 13 (36%) controls (P = NS). The
      cumulative percentage of patients with atrial fibrillation/flutter induced at
      each pacing cycle length was the same in each group. There was no difference in
      the duration of atrial fibrillation/flutter between control patients and patients
      with an AAVC. Among the 30 patients who underwent repeat atrial overdrive pacing
      after radiofrequency ablation of an AAVC, there was no difference in the
      inducibility or duration of atrial fibrillation/atrial flutter after ablation
      compared to baseline. CONCLUSION: These findings indicate that the vulnerability
      of the atrium to fibrillate in response to atrial pacing is independent of the
      presence of an AAVC.

PMID- 8269317
TI  - Morphology of the cardiac conduction system in patients with
      electrophysiologically proven dual atrioventricular nodal pathways.
AB  - INTRODUCTION: Although the electrophysiologic criteria for dual atrioventricular
      nodal pathways are well established, the anatomical substrate is still unclear.
      METHODS AND RESULTS: We examined the hearts from 10 patients who had been studied
      electrophysiologically prior to cardiac transplantation. All 10 patients were
      male, aged 22 to 60 years. Nine of the 10 patients had dual atrioventricular
      nodal pathways according to accepted criteria. Histologic studies of the
      atrioventricular conduction system showed normal structure of the
      atrioventricular node in all 10 hearts, with minor variations within the node in
      3 cases, within the penetrating bundle in 3 cases, and within the nonbranching
      bundle in 3 cases. The atrial approaches to the atrioventricular node were
      generally scanty in 6 hearts. The solitary case that was shown
      electrophysiologically to lack dual pathways had no obvious difference in the
      structure of the nodal area other than sparsity of transitional cells. We were
      unable to locate any extranodal atrial tracts as described by other
      investigators. CONCLUSION: The anatomical substrate for conduction over dual
      pathways may be too subtle to be detected by gross morphologic studies. Since
      dual pathways were unmasked in all patients but one during electrophysiologic
      studies, it may be that the potential for these pathways is ubiquitous.

PMID- 8269318
TI  - Transmission and reentrant activity in the sinoventricular conducting system and
      in the circumferential lamina of the tricuspid valve.

PMID- 8269319
TI  - Radiofrequency catheter ablation of atypical atrioventricular nodal reentrant
      tachycardia.
AB  - INTRODUCTION: Published reports of radiofrequency ablation of atypical
      atrioventricular nodal reentrant tachycardia (AVNRT) have been limited. We
      present our experience in 10 consecutive patients with atypical AVNRT who
      underwent radiofrequency ablation of the "slow" AV nodal pathway. METHODS AND
      RESULTS: There were 9 females and 1 male; their mean age was 44 +/- 19 years (+/-
      SD). The mean AVNRT cycle length and ventriculoatrial (VA) interval at the His
      position during AVNRT were 340 +/- 50 msec and 200 +/- 70 msec, respectively. The
      slow pathway was successfully ablated in all patients with a mean of 10 +/- 7
      radiofrequency energy applications in the posteroseptal right atrium near the
      coronary sinus os. The mean procedure duration was 100 +/- 35 minutes. There were
      no complications. In 4 patients, target sites were identified during sinus rhythm
      by mapping for possible slow pathway potentials. In the other 6 patients, target
      sites were identified by mapping retrograde atrial activation during AVNRT or
      ventricular pacing. The VA times at successful target sites were a mean of 45 +/-
      30 msec less than the VA time at the His catheter during AVNRT. There were no
      differences in success rate, number of radiofrequency energy applications, or
      procedure duration between patients in whom mapping was guided by possible slow
      pathway potentials or by retrograde atrial activation. During 6 +/- 3 months of
      follow-up, 1 patient had a recurrence of atypical AVNRT and underwent a second
      ablation procedure, which was successful. CONCLUSION: Radiofrequency ablation of
      atypical AVNRT can be safely and effectively accomplished when target sites are
      identified based either on possible slow pathway potentials during sinus rhythm
      or retrograde atrial activation times during tachycardia.

PMID- 8269320
TI  - A quantitative measurement of spatial order in ventricular fibrillation.
AB  - INTRODUCTION: The degree of organization in ventricular fibrillation (VF) is not
      known. As an objective measurement of spatial order, spatial correlation
      functions and their characteristic lengths were estimated from epicardial
      electrograms of pigs in VF. METHODS AND RESULTS: VF was induced by premature
      stimulation in five pigs. Electrograms were simultaneously recorded with a 22 x
      23 array of unipolar electrodes spaced 1.12 mm apart. Data were obtained by
      sampling the signals at 2000 Hz for 20 minutes immediately after the initiation
      of FV. Correlations between all pairs of signals were computed at various times.
      Correlation lengths were estimated from the decay of average correlation as a
      function of electrode separation. The correlation length of the VF in pigs was
      found to be approximately 4 to 10 mm, varying as fibrillation progressed. The
      degree of correlation decreased in the first 4 seconds after fibrillation then
      increased over the next minute. CONCLUSION: The correlation length is much
      smaller than the scale of the heart, suggesting that many independent regions of
      activity exist on the epicardium at any one time. On the other hand, the
      correlation length is 4 to 10 times the interelectrode spacing, indicating that
      some coherence is present. These results imply that the heart behaves during VF
      as a high dimensional, but not random, system involving many spatial degrees of
      freedom, which may explain the lack of convergence of fractal dimension estimates
      reported in the literature. Changes in the correlation length also suggest that
      VF reorganizes slightly in the first minute after an initial breakdown in
      structure.

PMID- 8269321
TI  - Mechanisms in simulated torsade de pointes.
AB  - A mechanism of torsade de pointes consisting of moving sites of reentrant
      excitation has been proposed on the basis of findings with a computer model.
      Substantial additions to that mechanism are now proposed based on further studies
      with the same model. The model simulated propagation, cycle length-dependent
      recovery of excitability, and slow propagation during incomplete recovery.
      Regions of relatively short and long recovery were assigned because of evidence
      of regional prolongation of recovery in long QT syndromes in which torsade de
      pointes is frequent. As previously reported, premature excitation in the short
      recovery region initially propagated independently, then entered the long
      recovery region and reentered the short recovery region distal to the site of
      origin. Reentrant excitation initiated a similar series of events, and serial
      reentry at systematically changing locations resulted in changing patterns of
      excitation compatible with the changing QRS waveform in torsade de pointes.
      Episodes terminated when reentrant excitation reached the end of unclosed short
      recovery paths, collided in closed paths, or encountered refractoriness in the
      presence of nonuniform short recovery. In this study, it was shown that
      excitation preceding reentry had important effects on the mechanism. These
      included reversal of the direction of serial reentry, bidirectional serial
      reentry, reentry at multiple sites from the same parent conditions, and
      occurrence of reentry without the requirement of slow propagation. Evidence for a
      Doppler shift of cycle lengths in regions from which serial reentry was receding
      or approaching was obtained. Sustained serial reentry was also demonstrated and
      is a possible mechanism for polymorphic ventricular tachycardia. Findings further
      define a possible mechanism of torsade de pointes.

PMID- 8269322
TI  - "AV nodal" reentry: Part I: "AV nodal" reentry revisited.
AB  - This review is the first of a two-part series of articles on "atrioventricular
      [AV] nodal reentry." The early clinical literature as well as the experimental
      studies are reviewed, and more recent morphologic data are presented, with the
      aim of clarifying whether the reentrant circuit is confined to the AV node, or
      consists in part of extranodal components. Most of the evidence supports the
      concept that atrial tissue is an essential link in the reentrant pathway.
      Arguments will be presented to indicate that within the AV node, the separation
      between antegrade and retrograde pathways is functional, not anatomical, and that
      both pathways are in electrotonic contact.

PMID- 8269323
TI  - "AV nodal" reentry: Part II: AV nodal, AV junctional, or atrionodal reentry?
AB  - The classical model of "atrioventricular (AV) nodal" reentrant tachycardia
      suggests that the reentrant circuit is entirely within the compact AV node and
      that AV nodal tissue is present proximal and distal to the circuit. Recent
      evidence from mapping studies and from examination of the effects of curative
      procedures, however, suggests that the upper end of the circuit uses perinodal
      atrial or transitional tissue. Moreover, the anatomical substrate of dual "AV
      nodal" pathways is likely to be the multiple connections between compact AV node
      and atrium rather than discrete intranodal pathways. The antegrade slow pathway
      appears to be situated at the posteroinferior approaches to the AV node in the
      region between the coronary sinus orifice and the tricuspid annulus. The
      retrograde fast pathway appears to be situated in the anterior atrionodal
      connections at the apex of Koch's triangle, close to the His bundle. The lower
      turnaround point of the circuit is likely to be within the AV node.

PMID- 8269324
TI  - Neural control mechanisms and vasovagal syncope.
AB  - Patients with recurrent unexplained syncope may have cardioinhibitory and
      vasodepressor responses provokable with head-up tilt with or without exogenous
      beta-adrenergic stimulation. Although these responses are believed to be neurally
      mediated, the neural mechanisms involved are poorly understood. Numerous studies
      have documented peripheral vasodilation, hypotension, and bradycardia at the time
      of syncope and several case reports have shown sudden withdrawal of
      vasoconstrictor sympathetic neural outflow to skeletal muscle in human subjects.
      In cats and rats, a similar response can be provoked with hemorrhage and is
      prevented by interruption of cardiac vagal C-fiber afferents. In dogs, however,
      section of these fibers does not prevent the development of a vasodepressor
      response. The provocation of vasodepressor syncope during nitroprusside infusion
      in a heart transplant recipient with presumed ventricular denervation also
      suggests that cardiac afferent nerves may not be required for the development of
      vasodepressor responses in humans. Other potential mechanisms include release of
      endogenous opioids or nitric oxide that may inhibit sympathetic nerve firing, and
      primary central nervous system activation (as in partial seizures) that triggers
      cardioinhibitory and vasodepressor responses. This article reviews our current
      understanding of the mechanisms involved in the development of neurally mediated
      syncope.

PMID- 8269325
TI  - Cardiac arrhythmias in Chagas' heart disease.
AB  - Chagas' disease is a chronic parasitosis affecting most Latin American countries.
      Its most important clinical manifestation is a late developing chronic
      myocarditis and, much less frequently, an early acute myocarditis. Chagasic
      myocardial damage is microfocal and disseminated throughout the heart. In most
      cases, the coexistence of areas of myocytic degeneration, inflammatory
      infiltration, and fibrosis suggests a permanent evolving process. Commonly,
      chronic chagasic myocarditis resembles a dilated cardiomyopathy, with
      characteristic ECG abnormalities (atrial and ventricular extrasystoles,
      intraventricular and/or AV conduction disturbances, and primary ST-T wave
      changes). Since myocardial damage is scattered throughout the heart, the ECG
      abnormalities (arrhythmias, conduction disturbances, and repolarization changes)
      are also representative of the widespread cardiac involvement. Thus, sick sinus
      syndrome, atrial extrasystoles, intraatrial conduction disturbances, and atrial
      fibrillation or flutter are common findings in different stages of the disease.
      At the ventricular level, both conduction disturbances and arrhythmias are
      conspicuous expressions of the myocardial damage. Right bundle branch block alone
      or in combination with left anterior hemiblock are the most common conduction
      defects. Further compromise of the conduction system can lead to different
      degrees of AV block. Chagas' disease is the main cause of bundle branch block and
      AV block in endemic areas. In advanced cases of Chagas' heart disease,
      ventricular premature contractions are extremely frequent, multiform, and
      repetitive (couplets and runs of ventricular tachycardia), and show R on T
      phenomenon. These arrhythmias are usually aggravated by increased sympathetic
      tone, implying an enhanced risk of cardiac sudden death among chagasic patients,
      which is sometimes the first manifestation of the illness. Chronic chagasic
      myocarditis is the leading cause of cardiovascular death, mostly as a consequence
      of heart failure and sudden death, in areas where the disease is endemic.

PMID- 8269326
TI  - Signal averaging in patients with coronary artery disease: how helpful is it?
AB  - In patients who have survived acute myocardial infarction, the presence of
      ventricular late potentials using the high resolution signal-averaged ECG
      indicates areas of slow conduction and delayed activation that may potentially
      serve as a substrate for malignant ventricular arrhythmias. Although detection of
      late potentials is technique specific, signal-averaged analysis in the time or
      frequency domain may be a useful index for risk stratification with regard to
      ventricular tachycardia or sudden cardiac death. The sensitivity and specificity
      of late potentials for this purpose may be enhanced by combination with other
      variables, such as left ventricular ejection fraction and presence of complex
      ventricular ectopy. Therefore, the presence of ventricular late potentials in
      postmyocardial infarction patients, particularly in those patients with impaired
      left ventricular function, identifies those patients who are at high risk of
      malignant ventricular tachyarrhythmias. However, the strategies for prevention of
      serious arrhythmia complications during follow-up need to be established. The
      negative predictive value of late potentials is very high. Thus, the absence of
      late potentials indicates a low propensity to sustained ventricular tachycardia
      or sudden death, even in the presence of complex ventricular ectopy.
      Interventions may therefore not be necessary or should even be avoided. The
      incidence of late potentials in patients with spontaneous or induced ventricular
      fibrillation is lower and, if present, less pronounced than in those with
      sustained monomorphic ventricular tachycardia. This presumably is due to a lower
      degree of conduction delay, which serves as a substrate for reentry. Therefore,
      the ability of the signal-averaged ECG to predict a propensity to ventricular
      fibrillation is limited. Despite these limitations, the signal-averaged ECG may
      be used as a risk predictor in evaluation of patients after myocardial
      infarction. Unfortunately, at least as far as time domain analysis is concerned,
      it cannot be used as an efficacy predictor for response to pharmacologic
      interventions. Further studies will determine whether other modes of signal
      averaged analysis can predict the response to drugs.

PMID- 8269327
TI  - Cranial nerves of the coelacanth, Latimeria chalumnae [Osteichthyes:
      Sarcopterygii: Actinistia], and comparisons with other craniata.
AB  - We reconstructed the cranial nerves of a serially sectioned prenatal coelacanth,
      Latimeria chalumnae. This allowed us to correct several mistakes in the
      literature and to make broad phylogenetic comparisons with other craniates. The
      genera surveyed in our phylogenetic analysis were Eptatretus, Myxine, Petromyzon,
      Lampetra, Chimaera, Hydrolagus, Squalus, Mustelus, Polypterus, Acipenser,
      Lepisosteus, Amia, Neoceratodus, Protopterus, Lepidosiren, Latimeria and
      Ambystoma. Cladistic analysis of our data shows that Latimeria shares with
      Ambystoma two characters of the cranial nerves. Our chief findings are: 1)
      Latimeria possesses an external nasal papilla and pedunculated olfactory bulbs
      but lacks a discrete terminal nerve. In other respects its olfactory system
      resembles the plesiomorphic pattern for craniates. 2) The optic nerve is
      plicated, a character found in many but not all gnathostomes. Latimeria retains
      an interdigitated partial decussation of the optic nerves, a character found in
      all craniates surveyed. 3) The oculomotor nerve supplies the same extrinsic eye
      muscles as in lampreys and gnathostomes. As in gnathostomes generally, Latimeria
      has a ciliary ganglion but its cells are located intracranially in the root of
      the oculomotor nerve, and their processes reach the eye via oculomotor and
      profundal rami. 4) The trochlear nerve supplies the superior oblique muscle as in
      all craniates that have not secondarily reduced the eye and its extrinsic
      musculature. 5) The profundal ganglion and ramus are entirely separate from the
      trigeminal system, with no exchange of fibers. This character has an interesting
      phylogenetic distribution: in hagfishes, lampreys, lungfishes and tetrapods, the
      profundal and trigeminal ganglia are fused, whereas in other taxa surveyed the
      ganglia are separate. The principal tissues innervated by the profundal nerve are
      the membranous walls of the tubes of the rostral organ. 6) As in lampreys and
      gnathostomes, the trigeminal nerve has maxillary and mandibular rami. Unlike all
      other gnathostomes surveyed, the trigeminal nerve of Latimeria lacks a sizable
      superficial ophthalmic ramus. Thus, Latimeria lacks the well-developed
      superficial ophthalmic complex reported in most other fishes. As in gnathostomes
      generally, the maxillary ramus of the trigeminal nerve fuses with the buccal
      ramus of the anterodorsal lateral line nerve to form the buccal+maxillary
      complex. We reject the term 'Gasserian ganglion', which is often applied to the
      fused profundal and trigeminal ganglion of tetrapods. 7) The abducent nerve
      innervates not only the lateral rectus muscle (a character common to
      myopterygians) but also the basicranial muscle. As we previously reported, it is
      probable that the basicranial muscle of Latimeria is homologous to the ocular
      retracter muscle of amphibians.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8269328
TI  - Relevance of adverb distribution for the analysis of sentence representation in
      agrammatic patients.
AB  - In this study, it is shown that functional categories are present in agrammatic
      grammar. Specifically, the verb-adverb order is investigated in three agrammatic
      patients by means of a constituent ordering task. It is shown that when the verb
      is in a nonfinite form, it either precedes or follows the specifier-like adverb
      (both positions are correct), but when the verb is finite, the adverb always
      follows it (which is the only possible order). The conclusions are that (i) a
      functional category (namely Inflection), which is responsible for the relative
      order verb-adverb (of the relevant class), must exist in agrammatic grammar, and
      (ii) agrammatic aphasia cannot be described as a syntactic impairment involving
      basic sentence structure.

PMID- 8269329
TI  - The breakdown of Japanese passives and theta-role assignment principle by Broca's
      aphasics.
AB  - Syntactic comprehension of various types of passive sentences by Japanese Broca's
      aphasic patients was investigated. Based on their performance on the so-called
      "possessive passive" and "indirect passive," we exemplified that the
      comprehension abilities of Broca's aphasics and agrammatic Broca's aphasics point
      to a distinction between the gapped and gapless passive, as is proposed in Kubo
      (1990). We proposed a new structural account of syntactic disorders in Japanese,
      based on the assumption that the Head parameter, the directionality parameter of
      theta-assignment, and the distinction between the internal argument and external
      argument are retained in the grammar of Broca's aphasics. We then demonstrated
      that Broca's aphasics interpret sentences by the argument structure of a
      predicate and by the canonical direction of the theta-assignment. It was also
      shown that the proposed principle can account for the Broca's aphasics'
      performance on other types of constructions and that it has many consequences for
      the language-universal account of syntactic deficits.

PMID- 8269330
TI  - Comprehension and acceptability judgments in agrammatism: disruptions in the
      syntax of referential dependency.

PMID- 8269331
TI  - Structural description of agrammatic comprehension.
AB  - The trace-deletion hypothesis (Grodzinsky, 1990) holds that the comprehension
      deficit apparent in most agrammatic aphasics results from the absence of traces
      at the level of S-structure. This paper reports a test of this hypothesis in a
      case study of an agrammatic aphasic. Two experiments--one using a sentence
      picture matching task, one using the truth-value judgment task-examined the
      comprehension of the matrix clause in center-embedded relatives such as, The
      tiger that chased the lion is big. These structures provide a crucial test of the
      trace-deletion hypothesis because comprehension of the matrix clause (i.e.,
      knowing that the tiger is big and not the lion) is predicted to be unimpaired.
      Contrary to this prediction, however, the results of the present work show that
      comprehension of the matrix clause in such sentences is significantly impaired.
      We argue that a revised version of the trace-deletion hypothesis proposed by
      Hickok (1992a,b) can explain the present data and other previously unaccountable
      findings.

PMID- 8269332
TI  - The breakdown of binding relations.

PMID- 8269333
TI  - Verb-argument structure processing in complex sentences in Broca's and Wernicke's
      aphasia.
AB  - We describe three experiments that explore the real-time access of verb-argument
      structures in a group of normal control subjects, a group of Broca's aphasic
      patients, and a group of Wernicke's aphasic patients. Specifically, we examine
      whether our subjects exhaustively access the thematic representations of verbs in
      active, passive, cleft-subject, and cleft-object sentences. We find that our
      normal control subjects and Broca's aphasic patients are sensitive to the
      thematic properties of verbs, regardless of sentence type. Our Wernicke's aphasic
      patients do not show on-line sensitivity to this lexical property. We discuss
      these results in terms of multiple resources dedicated to specific sentence
      processing devices, a possible semantic deficit in Wernicke's aphasia, and a
      double-dissociation between the operation of accessing a verb's thematic
      properties and the operation of computing the trace-antecedent relation.

PMID- 8269334
TI  - An on-line analysis of syntactic processing in Broca's and Wernicke's aphasia.
AB  - This paper is about syntactic processing in aphasia. Specifically, we present
      data concerning the ability of Broca's and Wernicke's aphasic patients to link
      moved constituents and empty elements in real time. We show that Wernicke's
      aphasic patients carry out this syntactic analysis in a normal fashion, but that
      Broca's aphasic patients do not. We discuss these data in the context of some
      current grammar-based theories of comprehension limitations in aphasia and in
      terms of the different functional commitments of the brain regions implicated in
      Broca's and Wernicke's aphasia, respectively.

PMID- 8269335
TI  - Professor P. M. C. James--an appreciation. His work in academic dental public
      health and the speciality.

PMID- 8269336
TI  - An example of the application of Markov models in dentistry--a prediction of the
      fate of molar teeth in 12-year-old Scottish children.
AB  - Markov analysis is a mathematical modelling technique which is particularly
      useful for predicting prognoses and probabilities of chronic diseases within
      populations. This paper applies Markov analysis to data concerning the condition
      of upper left permanent first molars in a group of individuals who were surveyed
      at age 12 and 15 years in Scotland by the Office of Population Censuses and
      Surveys. The Markov analysis predicted that in 1998, when the group of
      individuals would be 27 years old, 3.6 per cent of upper left first permanent
      molar teeth would be sound, 2.6 per cent would be decayed, 58.4 per cent would be
      filled and 35.4 per cent would be missing. A comparison of the Markov prediction
      for 18 year-olds in Scotland in 1989 with United Kingdom data for 16-24 year-olds
      published in 1988 indicated that the observed health status of the teeth was
      considerably better than that predicted by the Markov technique. The
      applicability of the Markov method to tooth status may therefore lie less in its
      ability to predict events as in being able to provide 'baselines' for future
      dental states in particular groups. Such an application of the Markov method
      could be used to determine whether dental deterioration among a group is
      occurring at a faster or slower rate than in the past.

PMID- 8269337
TI  - An investigation of non-response bias by comparison of dental health in 5-year
      old children according to parental response to a questionnaire.
AB  - Non-response bias is a potentially serious problem in studies involving human
      subjects. A parental questionnaire/negative consent form was used in a dental
      epidemiological survey of 5-year-old children in Leeds. The aim of this study was
      to determine whether and to what extent there was any variation in caries
      experience and oral cleanliness between responding and non-responding groups.
      6,494 children were examined and completed questionnaires were returned for 4,069
      (63 per cent). The response was higher for white children (65 per cent) than for
      Asian (39 per cent) and Afro-Caribbean children (45 per cent). Lower response
      rates were found from parents living in inner city areas associated with social
      deprivation. Children of non-responders had poorer oral cleanliness and higher
      caries experience (mean dmft). This study demonstrated that members of a non
      response group are likely to be substantially different from responders.

PMID- 8269338
TI  - Attendance patterns and dental health of parents and children.
AB  - Questionnaires were posted to the parents of 293 5-year-old children who had been
      dentally examined at school in Stretford, Manchester, UK. Replies were received
      from 195 addresses and consisted of 182 mothers and 149 fathers. The mothers who
      replied were divided into three groups; 99 who reported that they attended the
      dentist for regular check-ups, 38 who went for occasional check-ups and 45 who
      only went when having trouble. The mean numbers of decayed teeth of their
      children were 0.92, 1.50 and 2.00 respectively (p < 0.05) and the mean dmft
      scores were 1.36, 2.05 and 2.69 (p < 0.05). Fifty children whose mothers reported
      having 25 teeth or less had a mean of 2.12 decayed teeth compared with 1.06 for
      125 children whose mothers had 26 teeth or more (p < 0.01). The mean dmft scores
      for the two groups were 2.68 and 1.59 respectively (p < 0.05). In contrast,
      dividing the children into groups based on reported attendance patterns and
      numbers of natural teeth of their fathers did not show any significant
      differences in decayed teeth or dmft scores. It is concluded that the dental
      attendance pattern and dental health of the mother, but not of the father, are
      important influences on the dental health of 5-year-old children.

PMID- 8269339
TI  - An evaluation of the role of health visitors in encouraging dental attendance of
      infants.
AB  - A dental health campaign which aimed to increase the number of infants registered
      under capitation with general dental practitioners took place in the North
      Western Region. The aim of this study was to evaluate the effectiveness of health
      visitors in encouraging dental attendance of this age group. Facilitators in each
      of the 7 districts involved worked with general dental practitioners and health
      visitors to ensure referred infants were accepted. Health visitors completed a
      data collection form with each referral so that the names could be checked for
      subsequent registrations. Parents of 3,165 children were contacted between
      January and May 1991. Of those 76 per cent (2,412) were referred to general
      dental practitioners, but only 21 per cent of those names that could be checked
      were traced to dentists' lists by the end of the study period. Only 40 per cent
      of those claimed to be registered could be identified. Most dentists said they
      would welcome further campaigns to increase attendance of infants. Health
      visitors agreed that early referrals were appropriate, and this campaign may have
      contributed to the high number of registrations of 0-2-year-olds in the North
      Western Region.

PMID- 8269340
TI  - Changes in oral health conditions among 6- to 15-year-old children in Auvergne
      (France) 1987-1991.
AB  - A representative sample of 1,200 schoolchildren of Auvergne (France) ranging in
      age from 6 to 15 years was randomly selected. Dental caries experience was
      determined using the dft, DMFT and DMFS indices. The plaque index and the
      gingival index were also recorded. Comparison with an identical 1987 study
      enabled the changes in schoolchildren's dental health to be examined. Significant
      reductions were observed in all age groups for the DMFT and DMFS indices and in
      the 6-9-year-old group for the dft index. The mean DMFT score for 12-year-old
      children was 1.97 in 1991, as compared to the score of 4.62 reported in 1987
      (57.3 per cent reduction). While no significant variation was observed in the
      gingival index, the plaque index decreased significantly for the 7-14-year-old
      group. The comparison confirmed the trend to a lower caries experience in
      schoolchildren in Auvergne as in many Western European countries.

PMID- 8269341
TI  - Distribution of developmental defects of enamel on ten tooth surfaces in children
      aged 12 years living in areas receiving different water fluoride levels in Sri
      Lanka and England.
AB  - The prevalence of enamel defects on ten tooth surfaces per subject was recorded
      in 1990/91 in 12-year-old children living in areas which received drinking water
      containing either 0.1, 0.5 or 1.0 ppm F, in Sri Lanka and in England. In some
      communities, children of high and low socioeconomic groups were included. The
      teeth included were: 46, 14, 13, 12, 11, 21, 22, 23, 24 and 36; buccal surfaces
      only were examined. One examiner examined all the children under natural light
      using the modified DDE index (Clarkson and O'Mullane, 1989). Teeth were not
      especially cleaned or dried. A 10 per cent re-examination of subjects indicated
      that examiner reproducibility was good. Data were presented for 547 subjects (168
      in Sri Lanka and 379 in England). While the maxillary central incisors were
      affected most often in England and in the 0.1 ppm F area in Sri Lanka, this was
      not the case in the 0.5 and 1.0 ppm F areas in Sri Lanka where prevalence was
      highest in premolar and canine teeth. Demarcated and diffuse opacities
      predominated in the 1.0 ppm F areas in both countries, while hypoplastic lesions
      were prevalent in Sri Lanka in the 0.1 and 0.5 ppm F areas, especially in
      maxillary incisor teeth. Nearly half the lesions extended to more than one-third
      of the tooth surface in the 1.0 ppm F areas. The findings indicate that maxillary
      canine and premolar teeth are affected much more in high fluoride areas in Sri
      Lanka and it is suggested that this may be due to their later development
      relative to incisors and first molars.

PMID- 8269342
TI  - The outcome of school dental screening in two suburban districts of Greater
      Manchester, UK.
AB  - School dental screenings have been carried out in the community dental service
      for over eighty years but there have been very few evaluations of their outcome.
      The community dental service is now required to provide treatment only for those
      who have experienced difficulty in obtaining treatment in the general dental
      service. A follow up procedure to school dental screenings was designed to ensure
      that as many children in need of treatment as possible attended a general dental
      practitioner. The objective of this study was to evaluate the effectiveness of
      this procedure in persuading school children to attend a general dental
      practitioner. Data on the outcome of this follow up procedure were collected
      between May 1990 and March 1991 in Oldham and Tameside and Glossop. Of the 47,776
      pupils screened, 10,925 were considered to require treatment. General dental
      practitioners confirmed subsequent attendance by 2,083 (19 per cent) and
      attendance at community dental service clinics was confirmed for a further 363 (3
      per cent). A further 2,161 (20 per cent) were found to have received treatment at
      a rescreening held two to three months later. Of those referred for treatment,
      4,607 children (42 per cent) had received it within the three months following
      the screening, the majority having received care in the general dental service.

PMID- 8269343
TI  - A study of the implementation of the policy to refer children from the community
      dental service to the general dental service.
AB  - The aim of this study was to investigate the process of implementing the transfer
      of child patients from the community dental services to the general dental
      services, for dental care. A postal questionnaire investigated the current
      activities of district dental officers regarding the implementation of the
      transfer. Utilising data from the questionnaires, a series of interviews was set
      up with the following individuals in three districts: district dental officers,
      two community dental officers, the general manager of the family health services
      authority, the chairman of the local dental committee, and a general dental
      practitioner. The majority of respondent districts (65.3 per cent) reported
      procedures in place for the referral of children from the community dental
      services to the general dental services. Examination of the interview data
      revealed that the extent to which individual community dental officers
      implemented the referral process showed individual variation.

PMID- 8269344
TI  - The changing face of periodontal epidemiology.
AB  - From the time of the earliest civilisations, there has been documentation of
      diseases affecting the periodontal tissues. Yet it is only in the last 40 years
      or so that indices of the periodontal diseases were developed and the bacterial
      aetiology of gingivitis demonstrated. Epidemiological studies conducted in the
      1950's and 1960's gave us valuable data on the prevalence and incidence of the
      periodontal diseases and factors associated with their aetiology and progression.
      However, with the introduction of new periodontal indices and refinement of
      criteria amidst increasing periodontal research, our perspectives of periodontal
      epidemiology have changed. Advanced destructive periodontal disease is less
      prevalent than previously thought, so there has been a shift towards risk
      assessment and determination of disease susceptibility. The future is promising,
      and possible advances in clinical and microbiological epidemiological research
      are considered, along with study of the host response to bacterial challenge.

PMID- 8269345
TI  - Orthodontics and health: have we widened our perspectives?
AB  - Orthodontics has seen a change in perspective in the United Kingdom. The patient,
      provider and purchaser are considered in sequence when considering this change.
      The changes in oral health, wider knowledge and greater expectations have
      affected the patient's perspective. While, for the provider, changes in
      diagnosis, linked with outcome and stability of treatment, have resulted in the
      development of indices of treatment need and outcome and the need to consider
      intervention, based on health grounds, plus equity of care. The purchaser needs
      appropriate technology and manpower available to provide a service in the
      international perspective of limited resources for health care and has an
      increased interest in equity of care provided using state funding.

PMID- 8269346
TI  - Patterns of disease and treatment and their implications for dental health
      services research.
AB  - An expert panel examining future goals for oral and dental health services
      research in the United States, considered that high on the list of priorities
      should be investigations of public health solutions for the control of those
      diseases which are of low prevalence but high morbidity and mortality such as
      oral cancer, and those which are of high prevalence and social impact but which
      represent a lesser threat to health such as dental caries. Against the background
      of demographic population changes, the present overview first examines trends in
      caries experience in the United Kingdom and their research implications, and then
      trends in oral cancer and precancer. It is suggested that an opportunistic
      screening programme for the latter conditions could be a cost-effective, feasible
      and appropriate approach to their prevention. An existing computer simulation
      model for undertaking cost evaluation studies of alternative interventions is
      discussed and it is concluded that such a model could provide useful background
      data before a national pilot study of screening for oral cancer and precancer
      were embarked upon.

PMID- 8269347
TI  - Professor Philip J. Holloway: an appreciation of the man and his professional
      life 1949-92.

PMID- 8269348
TI  - Nutrition, diet and dental public health.
AB  - Nutrition and diet can affect teeth in three ways: by affecting the structure of
      teeth (and thus appearance), by causing dental caries and by eroding teeth. The
      importance of dietary sugars in causing dental caries is clearly established and
      a reduction in consumption of non-milk extrinsic sugars recommended by
      government. The Health Education Authority has played a major role in promoting
      this aspect of dietary advice. The structure of teeth is influenced by nutrition;
      much of the evidence for this being published by Mellanby and colleagues in this
      country. Interest in this topic has increased recently and it seems probable that
      malnutrition enhances susceptibility to dental caries, and possible that it
      increases susceptibility to enamel defects especially in areas with moderate to
      high levels of fluoride ingestion. The prevalence and severity of dental erosion
      is likely to be increasing in Britain. Preliminary studies indicated that
      fluoride helps to protect teeth against erosion, but more research is needed.

PMID- 8269349
TI  - Promoting water fluoridation.
AB  - The Department of Health published two reports in 1962 and 1969 confirming the
      effectiveness of water fluoridation in demonstration studies in Watford, Anglesey
      and Kilmarnock. By 1988, approximately 6 million consumers (12 per cent of the
      population of England and Wales) were receiving artificially fluoridated water,
      although much of that progress was the result of decisions taken by local
      authorities prior to the reorganisation of local government and the health
      service in 1973-74. The Water Fluoridation Act (1985) established a clear process
      for decision making which incorporated requirements for local consultation.
      National opinion surveys indicate that public support for fluoridation has
      increased from 66 per cent in 1980 to 79 per cent in 1992. Regional Fluoridation
      Publicity Action Groups will need to convince local decision makers of the extent
      of this public support.

PMID- 8269350
TI  - Dental health promotion for the United Kingdom in the year 2000.
AB  - Dental ill health will not be controlled by clinical intervention, therefore, it
      is important to improve the efficacy of the dental profession's preventive care.
      This will involve a much broader perspective than has been the case in the past
      and is encompassed by the term health promotion. This represents an attempt by
      the World Health Organization to convince all interested health professionals
      that health has political, social and environmental dimensions.

PMID- 8269351
TI  - Developing policy in an administrative health region.
AB  - The paper presents recent English health and social care legislation as observed
      by a dentist, in a post which carries no dental remit, but involves
      responsibility in a Regional Health Authority for a variety of care groups,
      including mental health, learning disabilities and geriatrics, for interagency
      working and implementation of legislative changes. It poses a series of questions
      for dentistry which might arise from these changes, from the perspective of an
      informed 'outsider' of the dental world working at a strategic level.

PMID- 8269352
TI  - The contrast in dental caries experience amongst children in the north west of
      England.
AB  - Professor Philip Holloway has an outstanding reputation in dental science which
      has led him to be asked to give his advice on dental matters in many different
      parts of the world. When he came to Manchester in 1964 he came to join the
      Department of Children's and Preventive Dentistry and the dental welfare of the
      children in the north west of England has remained one of his abiding central
      interests. This paper examines the information that has become available on the
      dental caries experience among children in north west England since the 1960s
      when Philip Holloway joined the department. The paper collates data on the
      dramatic reduction in caries prevalence and examines the distribution of dental
      caries in children today. In the 1990s, typically, only one quarter of children
      account for three quarters of the dental caries that is present. In the future,
      efforts should be concentrated on identifying groups of children within the
      population at risk to dental caries rather than trying to identify individuals. A
      recent reduction in the provision of restorative treatment amongst 5-year-old
      children is noted in this region of England and proposals for further research
      are discussed.

PMID- 8269353
TI  - The Canadian Cardiovascular Society and the maintenance of competence.

PMID- 8269354
TI  - Holter monitoring as valuable as EPS testing.

PMID- 8269355
TI  - The Maintenance of Competence (MOCOMP) Program.

PMID- 8269356
TI  - Canadian Task Force for Cardiovascular Science. A Joint Initiative of the Heart
      and Stroke Foundation of Canada and the Canadian Cardiovascular Society.

PMID- 8269357
TI  - Follow-up after patch aortoplasty for coarctation of aorta.
AB  - BACKGROUND: Patch aortoplasty (PA) for coarctation of aorta (COA) can lead to
      aneurysm formation at the repair site. X-ray, echocardiogram and computed
      tomography are unreliable for diagnosis of this complication. OBJECTIVE: To
      evaluate prospectively patients with PA for COA by magnetic resonance imaging
      (MRI) to detect presence of aneurysm at the repair site. DESIGN: All patients who
      underwent PA at the authors' institution were identified. MRI was performed in
      transverse and long axis oblique views on all patients except those who had, or
      were going to have, aortic angiography for other reasons. Details of the surgical
      procedure were obtained from the hospital records. RESULTS: Of the 18 patients
      studied, 15 had MRI and three had aortic angiography. Age at PA ranged from one
      week to 13.3 years (mean 6.3 years). The interval from PA to MRI or angiography
      was 9.5 years (range four to 12.5). No aneurysm was detected in any patient.
      Recoarctation was diagnosed in two patients not previously suspected but
      discovered on MRI. At PA the intimal shelf causing coarctation was either not
      excised or only minimally trimmed in 14 of 15 instances. CONCLUSIONS: The
      incidence of late aneurysm formation following PA for COA is low in the authors'
      patients, possibly due to minimal intimal damage at repair, although these
      patients should be followed longer. MRI was useful for assessment of aneurysm and
      restenosis.

PMID- 8269358
TI  - The use of intradermal carrageenan in calves to estimate the dose of oxindanac, a
      nonsteroidal anti-inflammatory drug.
AB  - A simple and humane model of inflammation, induced by the intradermal injection
      of 0.3 mL of sterile 2% carrageenan, was characterized in calves by measuring the
      volume of skin swelling plus histological analysis of skin biopsies. Carrageenan
      produced a biphasic increase in skin swelling, with an early edematous response
      followed by a more chronic cellular infiltrate. The swelling and sensitivity to
      pressure observed in the early response were suitable for testing the
      antiedematous and analgesic activity of a new nonsteroidal anti-inflammatory drug
      (NSAID), oxindanac. Pretreatment with intravenous oxindanac at doses from 0.5 to
      8.0 mg/kg reduced the volume of swelling and this reached statistical
      significance (p < 0.05) at 2 mg/kg. The ED50 and ED90 values for inhibition of
      the peak swelling volume (4 h) were estimated to be 1 mg/kg and 2 mg/kg,
      respectively. These compare with an ED90 of 2.0 mg/kg for inhibition of serum
      TxB2 production, an index of platelet cyclo-oxygenase activity. The dose of
      oxindanac required for antiedematous activity correlated, therefore, with maximal
      inhibition of serum TxB2. The analgesic activity of oxindanac reached no clear
      maximum response, but statistically significant difference (p < 0.05) from
      placebo was reached with doses of 2 mg/kg and above. It is concluded that
      intradermal carrageenan produced a simple, humane and useful model for dose
      estimation of a new NSAID in calves.

PMID- 8269359
TI  - Depletion of intramuscularly and subcutaneously injected procaine penicillin G
      from tissues and plasma of yearling beef steers.
AB  - Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine
      penicillin G/kg body weight were administered to yearling beef steers by
      intramuscular injection daily for five consecutive days were investigated. These
      dosages are in excess of product label recommendations, but are in the range of
      procaine penicillin G dosages that have been administered for the treatment of
      some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body
      weight intramuscularly, once daily, with a withdrawal period of five days. Based
      on the tissue residue data from this study, the appropriate withdrawal period is
      ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg
      body weight dose when administered intramuscularly to yearling beef steers. In a
      related study, 18 yearling beef steers received 66,000 IU of procaine penicillin
      G/kg body weight administered by subcutaneous injection, an extra-label treatment
      in terms of both dose and route of administration, typical of current practice in
      some circumstances. Deposits of the drug were visible at subcutaneous injection
      sites up to ten days after injection, with more inflammation and hemorrhage
      observed than for intramuscular injections of the same dose. These results
      suggest that procaine penicillin G should not be administered subcutaneously at
      high doses; and therefore a withdrawal period was not established for
      subcutaneous injection.

PMID- 8269360
TI  - The brucellosis and tuberculosis status of wood bison in the Mackenzie Bison
      Sanctuary, Northwest Territories, Canada.
AB  - Postmortem examinations were done on 51 wood bison (Bison bison athabascae)
      killed as part of a multidisciplinary research project in the Mackenzie Bison
      Sanctuary, Northwest Territories, Canada, between 1986 and 1988. There was no
      gross, histological or bacteriological evidence of brucellosis or tuberculosis in
      these bison. Traumatic lesions were seen in one calf that had been attacked by
      wolves and a second calf that had been gored. Antibody titers to Brucella abortus
      were not found in sera from these 51 animals or an additional 112 wood bison that
      were chemically-immobilized or killed in the Sanctuary between 1986 and 1990. The
      combined prevalence of the diseases in the population could not have exceeded
      5.95% for the necropsy survey to have missed finding at least one infected
      animal, and the prevalence of brucellosis in the population would have had to be
      less than 1.95% for the broader serological survey to have failed to find at
      least one reactor animal on the battery of tests. These results, and the
      cumulative epidemiological information on brucellosis and tuberculosis in bison,
      indicate that bovine brucellosis and tuberculosis are not enzootic in the wood
      bison population in and around the Mackenzie Bison Sanctuary, and suggest that
      the population is free of these diseases. However, this expanding population is
      at risk of contracting both diseases from the infected bison population in and
      around nearby Wood Buffalo National Park.

PMID- 8269361
TI  - Prevaccination bovine viral diarrhea virus titers and subsequent reproductive
      performance in dairy heifers.
AB  - The study was conducted to determine if there was a relationship between
      prevaccination bovine viral diarrhea virus (BVDV) titers in 14 month-old dairy
      heifers and time open during first lactation, length of the conception interval,
      fetal survival during the second pregnancy, and age at culling. Possible
      associations were analyzed using nonparametric survival methods and survival
      distributions were described using the product-limit (Kaplan Meier) methods.
      Regression analysis was used to estimate the correlation between pre- and
      postvaccination BVDV titers three years after vaccination. Evidence of exposure
      to BVDV prior to 14 months of age was demonstrated by serum-virus-neutralization
      titers greater than 1:4 for 97% and greater than or equal to 1:128 for 67% of the
      72 heifers followed. No correlation was found for 38 pairs of prevaccination and
      postvaccination titers (p = 0.76). The risk of being culled was high for heifers
      (n = 41) with very low (1:2-1:8) or very high (> or = 1:256) titers, but low for
      heifers (n = 31) with moderate (1:16-1:128) prevaccination titers (p = 0.098).
      Risk of subsequent fetal loss was high for heifers (n = 30) with very low (1:2
      1:16) or very high (> or = 1:256) prevaccination titers, compared to heifers (n =
      24) with moderate (1:32-1:128) titers (p = 0.084). These findings suggest that
      prevaccination exposure to BVDV eliciting either a very weak or a very strong
      serological response may contribute to subsequent reproductive inefficiency and
      an increased risk of culling.

PMID- 8269362
TI  - Effect of birthweight, total protein, serum IgG and packed cell volume on risk of
      neonatal diarrhea in calves on two California dairies.
AB  - The objective of the study was to determine if there was a relationship between
      hematological, immunological and physiological variables of newborn calves and
      risk of diarrhea during the neonatal period. Four hundred and seventeen heifer
      calves from two dairies (A and B) in the San Joaquin Valley of California were
      enrolled at birth and scored daily, to 28 days of age, for evidence and severity
      of diarrhea (0 to 3). Calves were weighted at birth and blood sampled at two to
      five days of age to determine packed cell volume (PCV), total protein (TP) and
      IgG serum concentration. The Cox proportional hazards model was used to determine
      if age at onset of the first diarrhea episode and length of the first episode
      were associated with the hypothesized variables (PCV, TP, IgG and birthweight).
      The IgG concentration was not associated with the age at onset of diarrhea (p =
      0.6052, Dairy A; p = 0.4393, Dairy B) but a high IgG concentration was associated
      with a decreased length of episode (p = 0.0325, Dairy A; p = 0.0912, Dairy B),
      particularly for calves born in the winter on dairy A (p = 0.0211). For calves
      born in the winter, those with either a high or a low birthweight had diarrhea at
      a younger age (p = 0.0102, Dairy A; p = 0.0020, Dairy B). Associations were also
      found for PCV and TP with both the age at onset and length of the first episode
      of diarrhea. Results suggest that parameters measurable at, or shortly after
      birth may have important prognostic value in evaluating risk of calf diarrhea.

PMID- 8269363
TI  - Epidemiological study of enzootic pneumonia in dairy calves in Saskatchewan.
AB  - A field study involving 325 calves from 17 dairy herds in Saskatchewan was
      conducted to determine the risk of enzootic pneumonia and to assess its
      association with a number of factors. Two different case definitions of pneumonia
      were used in the analyses: the first was based on producers' treatment risk
      (CASE1) and the second was based on semimonthly clinical examinations of calves
      by the research veterinarian (CASE2). The risk of pneumonia based on CASE1 was
      39% and on CASE2 was 29%. The measure of agreement between CASE1 and CASE2 at the
      calf level of analysis was poor (kappa = 0.24, SE = 0.02) and at the herd level
      of analysis was moderate (kappa = 0.40, SE = 0.12). The mortality risk from
      pneumonia was 1.8% and a variety of infectious organisms were isolated from
      pneumonic lungs. Twenty-seven percent of the calves had inadequate (total IgG <
      or = 800 mg/dL) levels of passively acquired antibodies as measured by radial
      immunodiffusion. The proportion of seropositive titers in calves within the first
      two weeks of age was 94% to parainfluenza 3 virus (PI3V) and bovine respiratory
      syncytial virus (BRSV), 73% to Pasteurella haemolytica (Ph), 68% to bovine viral
      diarrhea virus (BVDV), 67% to infectious bovine rhinotracheitis virus (IBRV), 46%
      to Mycoplasma dispar (Md), 44% to Haemophilus somnus (Hs), and 21% to Mycoplasma
      bovis (Mb). At the calf level of analysis and after adjusting for clustering,
      there was a negative association (p = 0.10) between the diagnosis of pneumonia
      based on CASE2 and total IgG levels and Ph titers (rPh).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8269364
TI  - Pathogenesis of porcine reproductive and respiratory syndrome virus infection in
      mid-gestation sows and fetuses.
AB  - Two experiments were undertaken to evaluate whether porcine reproductive and
      respiratory syndrome (PRRS) virus was able to cross the placenta and infect
      midgestation fetuses following intranasal inoculation of sows and whether PRRS
      virus directly infected fetuses following in utero inoculation. In experiment 1,
      eight sows between 45 and 50 days of gestation were intranasally inoculated with
      PRRS virus (ATCC VR-2332), and four control sows were inoculated with uninfected
      cell culture lysate. Virus inoculated sows were viremic on postinoculation (PI)
      days 1, 3, 5, 7 and 9, shed virus in their feces and nasal secretions, and became
      leukopenic. Sixty-nine of 71 fetuses from principal sows euthanized on PI day 7,
      14 or 21 were alive at necropsy and no virus was isolated from any of the
      fetuses. Two principal sows that farrowed 65 and 67 days PI delivered 25 live
      piglets and three stillborn fetuses. The PRRS virus was isolated from two live
      piglets in one litter. In experiment 2, laparotomies were performed on five sows
      between 40 and 45 days of gestation and fetuses were inoculated in utero with
      either PRRS virus alone, PRRS virus plus a swine serum containing PRRS
      antibodies, or uninfected cell culture lysate. Three sows were euthanized on PI
      day 4 and two sows on PI day 11. Viral replication occurred in fetuses inoculated
      with virus alone and was enhanced in fetuses inoculated with virus plus antibody.
      No virus was isolated from control fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269365
TI  - Feline leukemia virus detection by immunohistochemistry and polymerase chain
      reaction in formalin-fixed, paraffin-embedded tumor tissue from cats with
      lymphosarcoma.
AB  - The prevalence of feline leukemia virus (FeLV) antigen and DNA was assessed in
      formalin-fixed, paraffin-embedded tumor tissues from 70 cats with lymphosarcoma
      (LSA). Tissue sections were tested for FeLV gp70 antigen using avidinbiotin
      complex (ABC) immunohistochemistry (IHC); DNA was extracted and purified from the
      same tissue blocks for polymerase chain reaction (PCR) amplification of a 166
      base pair region of the FeLV long terminal repeat (LTR). Results were related to
      antemortem FeLV enzyme-linked immunosorbent assay (ELISA) for serum p27 antigen,
      anatomic site of LSA, and patient age. Viral DNA was detected by PCR in 80% of
      cases and viral antigen by IHC in 57% of cases. Seventeen cases were PCR-positive
      and IHC-negative; one case was PCR-negative and IHC-positive. Clinical records
      included FeLV ELISA results for 30 of 70 cats. All 19 ELISA-positive cats were
      positive by PCR and IHC; of the 11 ELISA-negative cats that were negative by IHC,
      seven were positive by PCR. When evaluated according to anatomic site, FeLV DNA
      and antigen were detected less frequently in intestinal LSAs than in multicentric
      and mediastinal tumors. Lymphosarcoma tissues from cats < 7 yr were several fold
      more likely to be positive for FeLV antigen by IHC than were tumors from cats >
      or = 7 yr. However, there was no significant difference in PCR detection of FeLV
      provirus between LSAs from cats < 7 yr and those > or = 7 yr.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8269366
TI  - The effectiveness of gentamicin or polymyxin B for the control of bacterial
      growth in equine semen stored at 20 degrees C or 5 degrees C for up to forty
      eight hours.
AB  - Semen from three stallions was used to evaluate the effectiveness of two
      antibiotics added to semen extender for samples stored at 20 degrees C or 5
      degrees C for up to 48 hours. Each ejaculate was divided into six different
      treatments: semen+extender (SE); SE+gentamicin (100 micrograms/mL); SE+polymyxin
      B (1000 units/mL); and each of the above treatments inoculated with Pseudomonas
      aeruginosa ATCC 27853. Sampling of diluted semen for bacteriological analysis was
      performed after 2, 8, 24 and 48 hours of preservation at either temperatures. The
      presence of nonspecific bacteria was noted after two hours in all SE aliquots.
      The number of bacteria did not change in samples stored at 5 degrees C, while in
      samples preserved at 20 degrees C, it increased by three to four times after 48
      hours. In semen aliquots treated with either of the antibiotics, the number of
      nonspecific bacteria was very low after two and eight hours at both temperatures.
      This number remained stable up to 48 hours at 5 degrees C, while an increase was
      noted at 24 and 48 hours at 20 degrees C. At 5 degrees C, the number of P.
      aeruginosa cells tended to decrease between 24 and 48 hours in SE aliquots. The
      presence of gentamicin or polymyxin B appeared to rapidly inhibit growth of P.
      aeruginosa. At 20 degrees C, growth of P. aeruginosa increased between 8 and 24
      hours in SE, while the presence of antibiotics almost completely inhibited the
      growth of the bacterium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269367
TI  - Virulence of Salmonella enteritidis phagetypes 4, 8 and 13 and other Salmonella
      spp. for day-old chicks, hens and mice.
AB  - Virulence of three Canadian poultry strains of Salmonella enteritidis, namely
      phagetypes (PT) 4, 8 and 13, and one Salmonella heidelberg strain was assessed in
      orally and intraperitoneally inoculated one-day old chickens and compared to the
      virulence of a human S. enteritidis PT 4 strain from the United Kingdom (UK). The
      two PT 4 strains were also compared in orally inoculated adult laying hens. In
      addition, orally inoculated Balb/c mice were used to evaluate virulence of the
      above strains and two strains of Salmonella typhimurium containing different
      plasmids. In orally inoculated one-day old chickens, the UK S. enteritidis PT 4
      strain was more virulent than the Canadian PT 4 strain. The UK PT 4 strain was
      also more virulent and invasive in adult laying hens than the Canadian PT 4
      strain. The S. enteritidis PT 8 strain and one S. typhimurium strain isolated
      from a chicken hatchery were the most virulent for orally inoculated Balb/c mice.
      This strain of S. typhimurium contained the 60 megadalton plasmid associated with
      virulence for Balb/c mice which was not present in the S. typhimurium strain
      isolated from a pig with septicemic disease.

PMID- 8269368
TI  - Selective parathyroidectomy of the dog.
AB  - Selective parathyroidectomy (PTX) is preferred to thyroparathyroidectomy (TPTX)
      when specific effects of parathyroid hormone depletion are being studied.
      However, because of the anatomic proximity of thyroid and parathyroid glands,
      TPTX often is performed, leaving animals depleted of thyroxine (T4) and
      calcitonin as well as parathyroid hormone (PTH). In the present study, six normal
      dogs had parathyroid tissue and about seven-eighths of thyroid tissue removed.
      This quantity of thyroid tissue was inadequate to maintain normal serum T4
      concentrations, despite allowance of 168 days for thyroid recovery. Five of six
      dogs with reduced renal mass had successful selective PTX and normal serum T4
      concentrations at 28 days, when one-half or more of thyroid tissue was spared. We
      conclude that with attention to the surgical technique, selective PTX can be
      achieved in a high percentage of dogs and sufficient thyroid tissue spared to
      maintain euthyroidism.

PMID- 8269369
TI  - Leukotriene B4 in cows with normal calving, and in cows with retained fetal
      membranes and/or uterine subinvolution.
AB  - Two experiments were performed to study the relationship between leukotriene B4
      (LTB4) synthesis and placental separation and uterine involution in the cow. In
      experiment I, the concentration and synthesis of LTB4 by caruncular tissue was
      lower in cows with retained fetal membranes (RFM cows, n = 11) than in cows that
      expelled the fetal membranes normally (NFM cows, n = 19). The presence of
      bacterial cell wall, especially of alpha-hemolytic streptococci and coagulase
      positive staphylococci enhanced LTB4 synthesis by allantochorion only in NFM
      cows. In the RFM group, Escherichia coli lipopolysaccharide decreased
      allantochorionic LTB4 synthesis. With caruncle, only epidermal growth factor
      increased LTB4 production in NFM cows. In experiment II, the caruncular and
      endometrial secretion of LTB4 was lower in cows with subuterine involution (SUI
      cows, n = 5) or cows with SUI and RFM (SUI+RFM cows, n = 4) than in cows with
      normal uterine involution (NUI cows, n = 8). This decrease was especially
      noticeable in the previously gravid horn. In the three uterine involution groups,
      there were no differences in LTB4 synthesis by caruncular tissue taken from the
      previously gravid horn. However, progesterone and a bacterial suspension of E.
      coli reduced the synthesis of LTB4. Estradiol had no effect on LTB4 synthesis at
      the end of the postpartum period. These results suggest that LTB4 may play an
      important role in both placental separation and uterine involution in cattle and
      LTB4 synthesis may be modulated by endocrine and bacterial factors.

PMID- 8269370
TI  - Immunohistochemical detection of porcine reproductive and respiratory syndrome
      virus using colloidal gold.
AB  - Two cytopathic agents were isolated on porcine alveolar macrophages following
      inoculation with homogenates of lung tissues from pigs showing respiratory
      problems. These isolates were identified as porcine reproductive and respiratory
      syndrome (PRRS) virus isolates by indirect immunofluorescence using a PRRS virus
      (PRRSV) specific monoclonal antibody (MAb) and were designated as LHVA-92-1 and
      LHVA-92-2. Immunogold electron microscopy using a porcine PRRS positive serum
      pool and protein A-gold resulted in an intense labelling of aggregates of viral
      particles. Dark specific cytoplasmic staining of porcine alveolar macrophages
      infected with both virus isolates could be observed by immunogold silver staining
      (IGSS) using the specific MAb. This method proved effective in detecting PRRSV
      antigens in several ethanol-fixed tissues of piglets intranasally inoculated with
      the supernatants of macrophages infected with each isolate. Immunogold silver
      staining was also successfully used for the detection of PRRSV antigens on
      sections of formalin-fixed paraffin-embedded lung tissues and on frozen sections
      of lungs. The present results indicate that colloidal gold may be useful for the
      identification and immunohistochemical detection of PRRSV in tissues.

PMID- 8269371
TI  - Serological evidence of bovine immunodeficiency-like virus infection in a sheep.
AB  - A six month-old sheep was entered into a control group in an experiment designed
      to study the effects of exposure to the bovine immunodeficiency-like virus (BIV).
      Anti-BIV antibodies were detected in the serum of this sheep prior to the start
      of the study; these antibodies persisted for 12 months at which time the animal
      was destroyed. The sheep was normal clinically and was grossly normal at
      postmortem examination. Blood from this sheep was inoculated into a recipient
      sheep which subsequently showed a transient anti-BIV antibody response beginning
      two months postinoculation. Sheep have been previously shown to produce anti-BIV
      antibodies after experimental inoculation with infected cell culture material or
      infected bovine blood and BIV infection was found in a sheep pastured with BIV
      infected cattle. In the present case there was no contact with cattle; the source
      of the infection was not identified.

PMID- 8269372
TI  - Equine cricoid cartilage densitometry.
AB  - The density of the cricoid cartilage from 29 equine larynges collected from an
      abattoir was determined by dual photon absorptiometry (DPA). Densities of the
      right and left cricoid cartilages were highly correlated. No correlation was
      found between age of the horse and the density of the cricoid cartilage.

PMID- 8269373
TI  - Tuberculosis in Canadian schools.

PMID- 8269374
TI  - School contact tracing following a cluster of tuberculosis cases in two
      Scarborough schools.
AB  - Ten refugee children from an extended family were diagnosed with active
      tuberculosis. The family had recently arrived in Scarborough from Somalia.
      Mantoux skin testing was organized by the local health department for students in
      the two schools the children attended. An eleventh active case was found on
      screening. The reactivity rate for children tested once was 1.2% for Canadian
      born students, and 14.6% for foreign-born students. Reactivity rates of students
      tested once were not significantly higher than those in comparison schools.
      Repeat skin testing of non-reactors revealed a conversion rate of 4.4%. This rate
      may be an overestimate as a result of the booster phenomenon. Increased risk of
      testing positive was associated with a history of BCG and being foreign-born in
      all schools. As rates of tuberculin reactivity have greatly increased in
      Scarborough schools since the early 1980s, it is recommended that health
      departments screen foreign-born students for tuberculosis upon entrance to
      school.

PMID- 8269375
TI  - [Tuberculin screening in a secondary school in Montreal following a case of
      pulmonary tuberculosis].
AB  - We planned a tuberculin testing in a secondary school, following student exposure
      to a fellow student suffering from pulmonary tuberculosis. A first group of 71
      students for whom exposure seemed greater, had an intradermal Mantoux test. Of
      these 71 students, 18 (25.3%) had a > or = 5 mm reactions; 52 went through a
      second test three months later, six of whom had a > or = 5 mm reaction. In light
      of the results of the screening in this first group, the tuberculin testing was
      offered to a second group of 108 students. In this second group, the result of
      the skin test was > or = 5 mm for 10 (9.3%) students. Out of 179 students, 34
      (19.0%) had a significative reaction. A > or = 5 mm reaction was significantly
      associated with being male, being born outside of Quebec and being a member of
      the first group screened.

PMID- 8269376
TI  - Post-BCG tuberculin testing: interpreting results and establishing essential
      baseline data.

PMID- 8269377
TI  - Leaving user fees behind.

PMID- 8269378
TI  - Epidemiology of influenza vaccination in Canada.
AB  - To assess influenza vaccine coverage among Canadian adults, questions about the
      fall/winter 1990-91 immunization campaign were added to the Statistics Canada
      1991 General Social Survey. A total of 11,924 usable responses were obtained
      (response rate 80%). Overall, an estimated 13.8% (95% CI 13.1-14.5) of the
      Canadian population surveyed and 44.8% (95% CI 42.7-46.9) of the population 65
      years of age and over received a "flu" shot during the fall/winter 1990-91
      immunization campaign. A logistic regression model run separately in populations
      less than 65 years of age and in populations 65 and over reveals that, by far,
      the major predictor for receiving influenza vaccine was a recommendation by a
      nurse or physician. Two major reasons listed by persons 65 and over for not
      receiving the flu vaccine were 1) the belief they hardly ever get the flu (39%),
      and 2) they fear side effects (22%).

PMID- 8269379
TI  - Unintentional house fire deaths in Alberta 1985-1990: a population study.
AB  - We extracted data from the Medical Examiner's files for all fire deaths in
      Alberta reported to the Medical Examiner's for the period 1985-1990. Of the 320
      fire deaths, 183 (57%) were unintentional deaths from house fires. The highest
      house fire death rates occurred in children 0-4 years and in adults > or = 80
      years of age (2.9 and 3.2 per 100,000 per year). The majority (53%) of fatal
      house fires occurred in single detached dwellings but the rate of fatal house
      fires was 9.0 times higher in moveable dwellings than in single detached
      dwellings. At least 61 (33%) of unintentional fatal house fires were caused by
      smokers' material. Blood alcohol levels above 0.8 g/L were found in 84 (59%) of
      victims tested and in 39 (76%) of victims of fires caused by smoking materials.
      143 (78%) house fire deaths were due, at least in part, to inhalation of toxic
      fumes. The cause of fatal house fires in Alberta is multifactorial. However,
      particular attention should be paid towards the lethal combination of cigarettes
      and alcohol in preventing these fires.

PMID- 8269380
TI  - Risk perception differences in a community with a municipal solid waste
      incinerator.
AB  - Using a community model of risk perception, we conducted an environmental risk
      perception survey in a community with an operating municipal solid waste
      incinerator to further understanding of community responses to technology
      perceived as "hazardous". The specific aims of the survey were to study attitudes
      to waste management (incineration in particular) and to identify sociological
      attributes which help shape community attitudes to the facility. Approximately
      one third of the community were unaware of the incinerator. Those unaware gave
      lower desirability ratings to incinerator technology than the aware group. About
      half of the aware group were concerned about the facility and rated the
      incinerator in the same way as those who were unaware; however, the remainder
      (the unconcerned) appear to have accepted the incinerator. The results of this
      cross-sectional study suggest that informing the public about technology
      perceived as hazardous may not lead to alarm, but may in fact increase
      acceptance.

PMID- 8269381
TI  - [Innovation in the Quebec's community health departments].
AB  - Following the reform of the health care system in Quebec at the beginning of the
      1970s, 32 Community Health Departments (departements de sante communautaire or
      DSC) were created; these new organizations were administratively and physically
      integrated into 32 acute care hospitals throughout the province. Our study
      investigates to what extent variations in the implementation of DSCs and in the
      way they have fulfilled their mandate influence the degree of innovation of their
      practices. The results show that DSCs devoting greater efforts to research
      activities and to their relationships with other health care establishments and
      agencies achieve a higher level of innovation in their practices.

PMID- 8269382
TI  - Promoting first trimester prenatal classes: a survey.
AB  - In June 1990, 436 women and their spouses attending prenatal classes in the
      Ottawa-Carleton region completed a self-administered questionnaire to identify
      use of and interest in first trimester prenatal classes, and possible contact
      points with women to encourage early prenatal class attendance. Only 23% of the
      women had attended classes during the first trimester, but another 39% said they
      would have been interested. Two major categories of deterrents to early prenatal
      class attendance were found: 1) low level of public knowledge about availability
      and usefulness and 2) low physician patient referral. Most (89.4%) women went to
      their physician early in pregnancy, and many (45.7%) found out they were pregnant
      through the drug store. Suggested approaches to promoting first trimester
      attendance at prenatal classes include public awareness campaigns through
      pharmacies, the workplace and in the general community, and education programs
      for physicians about the importance of referral to early classes.

PMID- 8269383
TI  - A swimming pool-associated outbreak of Cryptosporidiosis in British Columbia.
AB  - An outbreak of Cryptosporidiosis occurred over three months in a British Columbia
      community, peaking in December 1990. Results of the case-control study and
      illness surveys support the hypothesis that transmission occurred in a public
      children's pool at the local recreation centre. Analysis using lab-confirmed
      cases revealed a matched odds ratio of 4.5 [95% CI 0.97, 20.83], and using
      clinical cases an unmatched odds ratio of 12.8 [95% CI 3.68, 46.77], associated
      with swimming in the children's pool within two weeks prior to onset of illness.
      Other risk factors were not significant. Attack rates in various groups of
      children's pool users ranged from 8% to 78%. The children's pool was closed for
      steam cleaning and disinfection. Unusually frequent defecations including liquid
      stools had occurred before and during the outbreak. Improvements were instituted
      for removal of feces and superchlorination of pool water.

PMID- 8269384
TI  - A comparison of the health status of Riverdale residents with residents of the
      rest of Toronto based on the Toronto Community Health Survey.
AB  - OBJECTIVES: To compare the health status of Riverdale residents with residents of
      the rest of Toronto. DESIGN: Cross-sectional telephone survey. SETTING: Toronto.
      TIME FRAME: October 1988-June 1989. PARTICIPANTS: Four hundred and fourteen
      residents of Riverdale, a residential-industrial area of Toronto, and 866
      residents of the rest of Toronto, age 15 years and older in households with
      telephones. MAIN RESULTS: Respondents in Riverdale compared to respondents in the
      rest of Toronto were more likely to speak languages other than English, have less
      formal education, and be of Oriental ethnic origin. Perceived health status
      varied between the two areas, but no significant difference existed in diagnosed
      morbidity. Riverdale respondents were much more aware of food and soil
      contamination than respondents from the rest of Toronto.

PMID- 8269385
TI  - Smoking and loss of longevity in Canada.
AB  - This is a first attempt to calculate mortality rates and to construct life tables
      by smoking status for the Canadian population. U.S. mortality ratios (American
      Cancer Society) have been applied to the smoking proportions in Canada to obtain
      mortality rates for life table construction. Canadian proportions of never and
      ever smokers are available in the General Social Survey (1985 and 1991). The
      reduction in life expectancy at age 35 for the ever smoked group is 5.8 years for
      men and 3.7 years for women, for current smokers 8.5 years for men and 5.3 years
      for women and for former smokers 3.7 years for men and 2.0 years for women.
      Smoking compromises life expectancy at all ages though the greatest difference is
      observed between age 60 and 80. At age 35 years, the life expectancy is reduced
      between 10 and 20% for current smokers. This loss of life in the younger years is
      substantial and should be of concern from the point of view of promoting good
      health and prevention of disease.

PMID- 8269386
TI  - [Promotion of family physical activity in the municipal milieu: a study of
      population needs].
AB  - A needs analysis was completed for parents in six municipalities in Quebec in
      order to define population needs with respect to physical activity practices.
      There was a clear parental preference for activities at the same time as those of
      their children, either with or separate from them. The parents also noted their
      preference for outdoor, noncompetitive and unsupervised activities. These results
      agree with similar studies done elsewhere and will guide the development of a
      program promoting family activities at the municipal level.

PMID- 8269387
TI  - [Anti-tobacco day at the hospital: factors associated with smoking cessation].

PMID- 8269388
TI  - Need for hearing screening program?

PMID- 8269389
TI  - Nonculture methods for diagnosis of disseminated candidiasis.
AB  - Two of the nonculture approaches to the diagnosis of DC, enzymatic-fluorometric
      determination of serum D-arabinitol and detection of marker antigens in
      antigenemia (enolase and CWMP), have been commercialized and have shown promise
      in limited clinical trials. These approaches are not new but are the culmination
      of efforts made over 10 or more years. Clearly, further fine-tuning of both
      metabolite and antigen detection is needed to simplify the methods and to improve
      their sensitivity and specificity so that they will be valuable in guiding
      clinical treatment decisions. An alternative approach, detection of DC by DNA
      amplification methods such as PCR, is a special case of a compelling technology
      and one that is capable of standardization across microbial genera. The
      availability of simplified PCR diagnostic methods for DC remains a tantalizing
      prospect. Nevertheless, the development of methods to release DNA from very small
      numbers of Candida organisms in the blood in a form that is sufficiently free of
      inhibitors of PCR will require further intensive effort. The maturation of these
      converging laboratory approaches to nonculture diagnosis of DC leads to more
      optimism about the eventual use of these methods in clinical laboratories.

PMID- 8269390
TI  - Bacillus cereus and related species.
AB  - Bacillus cereus is a gram-positive aerobic or facultatively anaerobic spore
      forming rod. It is a cause of food poisoning, which is frequently associated with
      the consumption of rice-based dishes. The organism produces an emetic or
      diarrheal syndrome induced by an emetic toxin and enterotoxin, respectively.
      Other toxins are produced during growth, including phospholipases, proteases, and
      hemolysins, one of which, cereolysin, is a thiol-activated hemolysin. These
      toxins may contribute to the pathogenicity of B. cereus in nongastrointestinal
      disease. B. cereus isolated from clinical material other than feces or vomitus
      was commonly dismissed as a contaminant, but increasingly it is being recognized
      as a species with pathogenic potential. It is now recognized as an infrequent
      cause of serious nongastrointestinal infection, particularly in drug addicts, the
      immunosuppressed, neonates, and postsurgical patients, especially when prosthetic
      implants such as ventricular shunts are inserted. Ocular infections are the
      commonest types of severe infection, including endophthalmitis, panophthalmitis,
      and keratitis, usually with the characteristic formation of corneal ring
      abscesses. Even with prompt surgical and antimicrobial agent treatment,
      enucleation of the eye and blindness are common sequelae. Septicemia, meningitis,
      endocarditis, osteomyelitis, and surgical and traumatic wound infections are
      other manifestations of severe disease. B. cereus produces beta-lactamases,
      unlike Bacillus anthracis, and so is resistant to beta-lactam antibiotics; it is
      usually susceptible to treatment with clindamycin, vancomycin, gentamicin,
      chloramphenicol, and erythromycin. Simultaneous therapy via multiple routes may
      be required.

PMID- 8269392
TI  - Antifungal susceptibility testing.
AB  - Unlike antibacterial susceptibility testing, reliable antifungal susceptibility
      testing is still largely in its infancy. Many methods have been described, but
      they produce widely discrepant results unless such factors as pH, inoculum size,
      medium formulation, incubation time, and incubation temperature are carefully
      controlled. Even when laboratories agree upon a common method, interlaboratory
      agreement may be poor. As a result of numerous collaborative projects carried out
      both independently and under the aegis of the Subcommittee on Antifungal
      Susceptibility Testing of the National Committee for Clinical Laboratory
      Standards, the effects of varying these factors have been extensively studied and
      a standard method which minimizes interlaboratory variability during the testing
      of Candida spp. and Cryptococcus neoformans has been proposed. This review
      summarizes this work, reviews the strengths and weaknesses of the proposed
      susceptibility testing standard, and identifies directions for future work.

PMID- 8269395
TI  - Gram-negative sepsis: what dilemma?

PMID- 8269396
TI  - Ultrastructural localization of wheat germ agglutinin binding sites on the sperm
      surface of water buffalo (Bubalus bubalis). A fracture label study.
AB  - In the present study we have examined the plasma membrane surface organization
      employing fluorescein isothiocyanate linked wheat germ agglutinin (WGA) of the
      cauda epididymal and ejaculated spermatozoa of water buffalo. Intramembrane
      particle distribution pattern in the various segments of the spermatozoa has also
      been observed. WGA-ovomucoid gold has been used to study the distribution of
      sialoproteins on the sperm surface. With fracture label, WGA receptor sites have
      been identified on the fractured membrane halves of the sperm plasma membrane
      overlying the acrosome as well as the middle piece and the principle piece.

PMID- 8269394
TI  - An overview of nosocomial infections, including the role of the microbiology
      laboratory.
AB  - An estimated 2 million patients develop nosocomial infections in the United
      States annually. The increasing number of antimicrobial agent-resistant pathogens
      and high-risk patients in hospitals are challenges to progress in preventing and
      controlling these infections. While Escherichia coli and Staphylococcus aureus
      remain the most common pathogens isolated overall from nosocomial infections,
      coagulase-negative staphylococci (CoNS), organisms previously considered
      contaminants in most cultures, are now the predominant pathogens in bloodstream
      infections. The growing number of antimicrobial agent-resistant organisms is
      troublesome, particularly vancomycin-resistant CoNS and Enterococcus spp. and
      Pseudomonas aeruginosa resistant to imipenem. The active involvement and
      cooperation of the microbiology laboratory are important to the infection control
      program, particularly in surveillance and the use of laboratory services for
      epidemiologic purposes. Surveillance is used to identify possible infection
      problems, monitor infection trends, and assess the quality of care in the
      hospital. It requires high-quality laboratory data that are timely and easily
      accessible.

PMID- 8269397
TI  - Human aspirated epididymal spermatozoa: ultrastructural, immunological, kinetic
      study and fertilization ability. MESA Italian Group.
AB  - The analysis of ultrastructural, kinetic and immunological characters of
      spermatozoa aspirated from the proximal segments of the epididymis of patients
      with congenital absence of vas deferens showed that most of them are defective.
      These spermatozoa, utilized in different procedures of assisted reproduction,
      showed a reduced fertilization rate. The data obtained in this study seem to
      indicate that CAV affects the development and functional properties of epididymal
      spermatozoa.

PMID- 8269398
TI  - Chronic lead exposure induces ultrastructural alterations in the monkey testis.
AB  - The purpose of this study was to establish the effects of lead on the non-human
      primate testis. Sixteen cynomolgus monkeys maintained in environmentally
      controlled conditions were administered 1500 micrograms lead acetate/kg bw/day in
      gelatin capsules. Monkeys were randomly assigned to the following groups: control
      (n = 3), which received 95% glycerol and 5% distilled water (vehicle) over their
      lifetime for 9 years; infancy group (n = 4), exposure limited to the first 400
      days of life; post-infancy group (n = 5), dosed following 300 days of life to 9
      years of age; lifetime group (n = 4), dosed for nine years. All the animals were
      treated with lead or vehicle for the entire duration of the experiment. The
      organs from animals in the control group consisted of seminiferous epithelium
      comprised of typical Sertoli cells containing nuclei with numerous infoldings and
      longitudinally-oriented profiles of endoplasmic reticulum, microtubules,
      mitochondria, and lipid droplets that were scarce. Spermatogenic cell types at
      different developmental stages were observed. Seminiferous epithelium from
      animals of the treated groups exhibited distortion in the general architecture of
      the epithelium such that a marked decrease in its height was revealed. In
      particular, Sertoli cells contained heightened number of lipid droplets and
      lysosomal elements, and the basal lamina was usually stratified. The magnitude of
      alterations in the seminiferous tubules was indistinguishable among the three
      treated groups. These findings support the conclusion that lead is a potent
      testicular toxin.

PMID- 8269391
TI  - Human immunodeficiency virus type 1 infection of the brain.
AB  - Direct infection of the central nervous system by human immunodeficiency virus
      type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early
      years of the AIDS epidemic. Neurological complications associated with AIDS were
      largely attributed to opportunistic infections that arose as a result of the
      immunocompromised state of the patient and to depression. In 1985, several groups
      succeeded in isolating HIV-1 directly from brain tissue. Also that year, the
      viral genome was completely sequenced, and HIV-1 was found to belong to a
      neurotropic subfamily of retrovirus known as the Lentivirinae. These findings
      clearly indicated that direct HIV-1 infection of the central nervous system
      played a role in the development of AIDS-related neurological disease. This
      review summarizes the clinical manifestations of HIV-1 infection of the central
      nervous system and the related neuropathology, the tropism of HIV-1 for specific
      cell types both within and outside of the nervous system, the possible mechanisms
      by which HIV-1 damages the nervous system, and the current strategies for
      diagnosis and treatment of HIV-1-associated neuropathology.

PMID- 8269399
TI  - Experimental schistosomiasis mansoni: characterization of connective tissue cells
      in hepatic periovular granulomas.
AB  - Connective tissue cells present in periovular granulomas, induced in mice livers
      by schistosomal infection, were studied in situ and in an in vitro culture after
      cell migration from explanted granulomas. They were compared to cells of the
      adjacent hepatic tissue. Connective tissue cells in granulomas and granuloma
      derived primary cell lines were characterized as myofibroblasts. The presence of
      lipid droplets in cells of early granulomas, and comparison with adjacent
      perisinusoidal cells, indicated their origin through activation and mobilization
      of lipocytes from the adjacent hepatic tissue. This origin was confirmed in long
      standing cultures of granuloma-derived cells, in the stationary phase of growth,
      in which myofibroblasts could return spontaneously into the fat-storing
      phenotype.

PMID- 8269400
TI  - Epithelial surface changes and induction of gallstones in the male Syrian hamster
      gallbladder as a result of a two-month sex steroid treatment.
AB  - Transmission (TEM) and scanning (SEM) electron microscopic observations were
      correlated to characterize morphologic changes induced in the gallbladder of male
      Syrian hamsters following a two-month estradiol (E) and estradiol +
      medroxyprogesterone (E + MP) treatment. Compared to control (C), E-treated
      surface epithelial cells show pleomorphism, cytoplasmic vacuolizations, apical
      granules, excrescences and decapitations, and small gallstone-like deposits.
      Following both E + MP treatment, a large accumulation of apical granules
      containing acidic mucoid products, abundant intraluminal deposits and numerous
      fields of observation suggest that cell debris and mucous condensation could
      participate in the formation of the large intraluminal gallstone-like deposits
      detected as a result of this treatment. In control gallbladders these events were
      never observed. MP added to E also increases liver and gallbladder weight as well
      as blood lipid levels. These findings complement and confirm other previous data
      obtained following short steroid treatment in male, ovariectomized and intact
      female hamsters. In addition, these results support our hypothesis that gallstone
      nucleation and growth originate from multiple factors, hormonal disturbance,
      modulation of liver lipid metabolism, production of cell debris and mucus, can be
      responsible for the initial gallstone nucleation.

PMID- 8269393
TI  - Epidemiologic evidence for multiple sclerosis as an infection.
AB  - The worldwide distribution of multiple sclerosis (MS) can be described within
      three zones of frequency: high, medium, and low. The disease has a predilection
      for white races and for women. Migration studies show that changing residence
      changes MS risk. Studies of persons moving from high- to low-risk areas indicate
      that in the high-risk areas, MS is acquired by about age 15. Moves from low- to
      high-risk areas suggest that susceptibility is limited to persons between about
      ages 11 and 45. MS on the Faroe Islands has occurred as four successive epidemics
      beginning in 1943. The disease appears to have been introduced by British troops
      who occupied the islands for 5 years from 1940, and it has remained
      geographically localized within the Faroes for half a century. What was
      introduced must have been an infection, called the primary MS affection (PMSA),
      that was spread to and from successive cohorts of Faroese. In this concept, PMSA
      is a single widespread systemic infectious disease (perhaps asymptomatic) that
      only seldom leads to clinical neurologic MS. PMSA is also characterized by a need
      for prolonged exposure, limited age of susceptibility, and prolonged incubation.
      I believe that clinical MS is the rare late outcome of a specific, but unknown,
      infectious disease of adolescence and young adulthood and that this infection
      could well be caused by a thus-far-unidentified (retro)virus.

PMID- 8269401
TI  - Subcellular organization of the placenta in the Atlantic sharpnose shark,
      Rhizoprionodon terraenovae.
AB  - The Atlantic sharpnose shark, Rhizoprionodon terraenovae, is a viviparous
      anamniote that develops a yolk sac placenta composed of: a) uterine mucosa, b)
      egg envelope and c) fetal yolk sac mucosa. The transporting uterine mucosa is a
      squamous epithelial bilayer with prominent lateral and basal infoldings between
      contiguous cells. The surface cells have prominent secretion vesicles that empty
      their contents to the exterior. Immediately beneath the epithelium is a basal
      lamina and a profuse vascular supply with a continuous endothelium. The
      epithelium of paraplacental uterine sites is mucous. The tertiary egg envelope is
      retained throughout gestation and separates the distal part of the yolk sac from
      the maternal uterine mucosa. The egg envelope is compact on the yolk sac surface
      but displays delaminations on the uterine surface. The fetal yolk sac is composed
      of two portions, viz., a proximal, saccular region and a heavily vascularized,
      rugose, distal portion. The proximal portion has ultrastructural characteristics
      of a steroid hormone producing tissue, including massive smooth endoplasmic
      reticulum frequently forming whorled arrays. However, definitive evidence that
      the yolk sac is an endocrine organ is lacking. The distal portion of the fetal
      yolk sac is composed of a squamous epithelial bilayer that is separated from the
      underlying vascular network by a continuous basal lamina. The endothelium of the
      vessels is fenestrated. Cytoplasmic characteristics of these cells include an
      extensive Golgi complex, smooth walled caveolae, vesicles with electron-dense
      contents that are presumably endocytotic in nature and dense bodies that are
      suggested to be lysosomes that are involved in the digestion of material that may
      be yolk metabolites.

PMID- 8269402
TI  - Fine structure of the term umbilical cord in the Atlantic sharpnose shark,
      Rhizoprionodon terraenovae.
AB  - The fine structure of the umbilical cord and appendiculae in the Atlantic
      sharpnose shark, Rhizoprionodon terraenovae, is examined by light, scanning and
      transmission electron microscopy. During ontogeny of placental sharks, the yolk
      sac and stalk become progressively modified as a functional hematrophic placenta
      and umbilical cord respectively. In most placental sharks the umbilical cord is
      smooth. In the Atlantic sharpnose shark, the epithelial ectoderm of the
      somatopleure forms richly vascularized extensions termed appendiculae. Scanning
      electron microscopy reveals that the base and shaft of appendiculae are flattened
      while the distal portion may be expanded to form one to three lobes. The surface
      of appendiculae is composed of two distinct cell types, the most plentiful are
      microvillar cells. The second cell type contains prominent granules. These cells
      are much larger than the former and are partially submerged below the surface,
      except for the cell apex. These cells undergo secretory cycles ending in
      expulsion of their contents. The possible function of the granulated cells is
      discussed. The umbilical cord contains an umbilical vein, umbilical artery,
      ductus vitellointestinalis and extraembryonic coelom. The endodermal ductus
      initially conveys yolk from the yolk sac to the fetal gut by activity of ciliated
      cells lining it. The ductus persists in the adult. Microvillar cells, also
      present in the ductus, may play a role in the absorption of yolk metabolites
      early in development, prior to yolk depletion. Enteroendocrine cells are wedged
      between the ciliated and microvillar cells. These cells may exert paracrine
      regulation of local areas of the ductus.

PMID- 8269403
TI  - Myofibrillar breakdown and cytoskeletal alterations in heart muscle cells during
      invasion by Trypanosoma cruzi: immunological and ultrastructural study.
AB  - The cytoskeletal organization of normal and Trypanosoma cruzi-infected mouse
      embryo heart muscle cells (HMC) in primary culture was investigated using
      immunofluorescence and transmission electron microscopy. Fluorescent probes
      revealed that in the early stages of infection, up to 24 h, the HMC cytoskeleton
      appeared to accommodate the intracellular parasites perinuclearly, with only a
      few cells displaying a slight disturbance in the distribution of filaments.
      However, as the infection progressed (48 to 72 h), microtubules and desmin
      filaments were disrupted. Breakdown of myofibrils occurred in regions where the
      parasites were present, followed by formation of actin polygons. Using Triton X
      100 treated whole cell mount, we obtained a striking preservation of the three
      dimensional architecture of the cytoskeleton. Combining electron spectroscopic
      imaging (ESI) with contrast tuning, we detected a highly interconnected
      cytoskeletal network in normal cells, and a loose network in infected cells.
      Bundles of filaments running under and over the parasites were also observed. Our
      results demonstrate that T. cruzi infection induces myofibrillar breakdown and
      destruction of several cytoskeleton filaments in heart muscle cells.

PMID- 8269404
TI  - Cardiac ultrastructure and electrocardiogram of the short-tailed shrew, Blarina
      brevicauda.
AB  - The smaller species of shrews have been of considerable interest to scientists
      because of their high rate of metabolism, structure-functional and behavioral
      adaptations to support their energy demands. The present data are the first
      detailed cardiac ultrastructural findings and electrocardiographic (ECG) data of
      adult and immature small short-tailed shrews, Blarina brevicauda. The heart is
      morphologically elongated and heart rates in excess of 900 b/min were observed,
      but ECG components and pattern are non-distinctive for this species.
      Ultrastructurally, the sarcomeres, tubular and sarcotubular systems and Purkinje
      cells resemble closely those observed in larger, less active mammals. Several
      distinctive features resembling those seen in some other shrews or hummingbirds
      exist, including reduced quantities of myocyte glycogen, irregularly shaped and
      tightly packed mitochondria, increased neural and vascular elements in the
      myocardium, and small size and unusual dispersion of atrial specific granules.
      These morphologic findings suggest that the remarkable physiologic performance of
      the heart of Blarina brevicauda is supported by a combination of macroscopic,
      histologic and cellular adaptations.

PMID- 8269405
TI  - Ultrastructural investigations on the vitellaria of the digenean Dicrocoelium
      dendriticum.
AB  - The paired vitellaria of the parasitic plathelminth Dicrocoelium dendriticum are
      composed of numerous follicles each of which contains vitellocytes at different
      stages of maturation and is enveloped by a basal lamina-like structure and a
      cytoplasmic sheath. The differentiation process of vitellocytes has been
      subdivided into three stages on the basis of morphological and functional
      characteristics. Stage I vitellocytes have a high nucleo/cytoplasmic ratio and a
      poorly differentiated cytoplasm mainly packed with free ribosomes. Stage II
      vitellocytes differentiate and increase in volume. Extensive RER and small Golgi
      complex appear and produce vesicles with an electron-dense content which fuse and
      give rise to large multigranular inclusions. Stage III vitellocytes are about to
      enter the vitelloduct, their cytoplasm is almost completely filled with the
      multigranular inclusions whose content reacts positively to the test for
      polyphenols. The inclusions are therefore interpreted as egg-shell globules.
      Mature vitellocytes also contain a small number of lipid droplets which are
      sometimes surrounded by a few polysaccharide particles, but completely lack
      protein yolk globules. The role of vitellocytes of D. dendriticum in egg-shell
      formation and embryo nutrition is discussed.

PMID- 8269406
TI  - Cyclosporin-induced gingival hyperplasia: an ultrastructural study of the oral
      epithelial prickle cells.
AB  - In this study the ultrastructural characteristics of the prickle cells of the
      human gingival epithelium after cyclosporin-A treatment are described. The
      prickle cell layer shows hyperplasia, along with the well known hyperplasia of
      the connective tissue components. The prickle cells show large numbers of free
      ribosomes, rough endoplasmic reticulum profiles and well developed Golgi
      complexes. The intercellular space is usually large and the neighboring cells are
      joined by desmosomes. In many cases the intercellular space is almost diminished
      and the cells are joined by a lot of desmosomes. Occasionally, a single cilium
      was observed to project into the intercellular space but the functional
      significance of this observation is unknown. The tonofilaments exhibit a specific
      arrangement in the cytoplasm of the prickle cells and it is believed that they
      contribute to the formation of a 'tonofilament network' which, along with the
      desmosomes, provide strength to the epithelium. Possible mechanisms regarding the
      gingiva overgrowth are discussed.

PMID- 8269407
TI  - Reflux esophagitis in children: a scanning and transmission electron microscopy
      study.
AB  - In children, excess of gastroesophageal reflux causes lesions of the esophageal
      mucosa that we have studied by scanning and transmission electron microscopy (SEM
      and TEM respectively) in 27 grasp biopsies prelevated during endoscopic
      procedures. Ultrastructural lesions can be graded on the basis of their severity.
      In grade I, epithelial cells are well preserved in the deepest layers whereas the
      superficial cells display ultrastructural alterations such as irregular
      microridges or reduced intercellular junctions. In grade II, the surface is
      composed of extruding cells and in the intermediate layer, large intercellular
      spaces containing lympho-monocytic cells are visible. In grade III, the mucosal
      surface is characterized by crater-like erosions, degenerating cells are visible
      in all the layers; in two patients columnar epithelium-lined areas (Barrett's
      esophagus) have been identified. Our results suggest that in patients with reflux
      esophagitis, ultrastructural examination of grasp biopsies prelevated by
      pediatric endoscopes allows a grading of the anatomical lesions providing data
      that can not be obtained by conventional histology.

PMID- 8269408
TI  - Trypanosoma cruzi-heart muscle cell interaction: the presence of two or more
      trypomastigotes within a single endocytic vacuole.
AB  - Ultrastructural studies of the interaction between T. cruzi clone Dm28c and heart
      muscle cells (HMC) showed that in the initial phase of the cell recognition
      process several parasites could be found attached to a focal point on the surface
      of the host cell. Immediately following this phase, two or more parasites could
      be detected inside the same endocytic vacuole by electron spectroscopic imaging
      (ESI).

PMID- 8269409
TI  - The bladder wall under extreme stress condition: ultrastructural observations in
      a hibernating mammal.
AB  - Comparative ultrastructural observations are presented of the distended bladder
      of a hibernating dormouse (Muscardinus avellanarius) and a relaxed organ taken
      from an active animal. The distended bladder of the hibernating animal has an
      extremely thin wall lined with a three-layer urothelium. An osmiophilic coat
      lines the luminal surface of the urothelium in the hibernating animal, but it is
      very thin indeed in the specimen from the active dormouse. In the urothelium of
      the distended bladder, a larger number of fusiform vesicles (FVs, typical
      structures of the urothelium with asymmetric unit membrane) is found. On the
      contrary, lysosomes, multivesicular bodies, and interdigitation of plasma
      membrane between adjacent cells are all more frequent in the relaxed bladder of
      the active dormouse. Results suggest that hibernating animals can be a useful
      model for investigating the biology of epithelial cells in the mammalian bladder.

PMID- 8269410
TI  - Unity in diversity.

PMID- 8269411
TI  - Rigid head pin fixation for infants undergoing neurosurgery.

PMID- 8269412
TI  - Silicon membrane interpositioning for the prevention of skull deformity following
      experimental craniosynostosis.
AB  - The interposition of various materials to complete suturectomy for the treatment
      of craniosynostosis has been used by many surgeons to prevent early postoperative
      reunion. Convincing scientific proof of the value of this procedure is still
      required, however. In this study a previously described model of experimental
      craniosynostosis was employed to examine the effects of an interposed silicon
      membrane in preventing skull deformity. Eighteen newborn rabbits had their right
      coronal sutures resected and the skulls were examined for shape and histology up
      to 6 months of age. The interposing of a silicon membrane was found to prevent
      formation of skull deformity during growth.

PMID- 8269413
TI  - Craniosynostosis as a risk factor.
AB  - Craniosynostosis is a little known organic factor in sociopathy. This factor
      should be among those taken into consideration in selecting patients to undergo
      craniotomy. Among 22,000 skulls of neuropsychiatric patients, there were 100 with
      premature coronal synostosis, compared with 57 with dolichocephaly. Thirty-seven
      of the 100 patients with coronal synostosis exhibited disorders of social
      adaptation; frontal cortex functions are assumed to be involved. There were 34
      cases of mental deficiency, 21 cases of psychosis, 13 of cerebral vascular
      disease, 10 cases of epilepsy, 4 of acrocephalosyndactyly, 3 of decompensation by
      slight craniocerebral trauma, and 1 case of ependymoma of the IV ventricle.
      Dolichocephalic patients exhibited a stronger tendency towards depressive states
      and cerebral vascular disease. The risks of cosmetic impairment and resulting
      psychosocial problems are discussed; especially in girls with oxy- and
      scaphocephaly craniofacial correction, is indicated, as it is also in patients
      with Saethre-Chotzen syndrome. In cases of premature synostosis of the coronal
      suture or synostosis of several sutures for carrying out a craniotomy, it is
      advisable to employ a combination of orbito-frontosphenoidal osteotomy for
      extension of the anterior cranial fossa. Craniosynostosis is a risk factor which,
      depending on the individual case and the sex and age of the patient, can impair
      central nervous functions, social adaption, and the blood supply of the brain.

PMID- 8269414
TI  - Tethered cord after spina bifida aperta: a longitudinal study of somatosensory
      evoked potentials.
AB  - Progressive neurological deterioration may occur after meningomyelocele repair.
      Magnetic resonance imaging almost invariably demonstrates a conus medullaris in
      an abnormally low position, whether neurological symptoms develop or not. Surgery
      of a secondary tethered cord is indicated when progression of neurological
      symptoms is documented. We performed a longitudinal study of posterior tibial
      nerve somatosensory evoked potentials (SSEPs) in children and adolescents after
      neonatal meningomyelocele repair. All patients were able to walk. Declining or
      negative posterior tibial nerve SSEPs were recorded in 15 patients; 14 of these
      had clinical signs of a secondary tethered cord. After surgery of the tethered
      cord, the SSEPs improved in 8 of 10 patients. Posterior tibial nerve SSEPs may
      contribute to the diagnosis of secondary tethered cord. After untethering, the
      evoked potentials demonstrate recovery of spinal cord function and might help to
      delineate prognosis.

PMID- 8269415
TI  - Ventriculo-gallbladder shunts in children.
AB  - Ventriculoperitoneal shunts are the most common procedure for the treatment of
      hydrocephalus. Ventriculoatrial shunts are effective but are subject to a higher
      incidence of potentially serious complications. We report our experience with
      ventriculo-gallbladder shunts in children. Ventriculo-gallbladder shunts are
      safe, effective, and technically easy to perform. We recommend their use when
      ventriculoperitoneal shunts have failed or the peritoneal cavity is not adequate
      for shunting.

PMID- 8269416
TI  - Optico-hypothalamic glioma: an analysis of 16 cases.
AB  - We reviewed our experience of 16 patients with histologically proven optico
      hypothalamic gliomas. They ranged in age from 0.3 to 15 years at the time of
      diagnosis. Fifteen tumors were located in the optic chiasm, optic nerve, optic
      tract and/or hypothalamus, while one tumor was confined to one optic nerve. All
      tumors were classified as low-grade astrocytomas, which were mainly composed of
      pilocytic astrocytes. No patient had associated neurofibromatosis. The initial
      treatment for tumors included surgery in 12, radiotherapy in 7, and chemotherapy
      in 4 patients. After treatment, visual function improved in 3 out of 14, and
      endocrine function improved in 1 out of 4 evaluable patients. The 5-year
      actuarial survival rate was 84.0%, and that at 10 years 71.1%. Our experience and
      the literature indicate that: (1) patients with disease limited to the optic
      nerve are adequately managed by resection alone; (2) chiasmal-hypothalamic
      gliomas behave variably, and progressive disease may occur late in the course of
      the illness; (3) gliomas that arise in patients under 2 years of age and involve
      the optic chiasm may act aggressively despite their histological benignity; (4)
      the beneficial effects of radiotherapy occur in about half of the patients; (5)
      although chemotherapy may be an effective adjuvant treatment modality, it is not
      an alternative to radiation therapy at present. Both surgery and irradiation
      therefore offer the best treatment now available for patients with progressive
      disease.

PMID- 8269417
TI  - Relational and therapeutic aspects of children with late onset of a terminal
      disease.
AB  - The authors studied the patterns by which children and adolescents with spinal
      amyotrophy face their disease and the psychological difficulties involved. Five
      case histories regarding forms II and III of spinal amyotrophy are discussed in
      detail. Intense and recurrent anguish about death and the image of a
      narcissistically injured self were found to be present in all patients. We
      believe that these are the emotional elements that are most important in
      influencing the development of the child's relations with his own mental objects.
      This should be taken into account in any type of approach to the treatment of
      patients with this disease.

PMID- 8269418
TI  - Stereotactic techniques in managing pediatric brain tumors.
AB  - Stereotactic techniques available for managing pediatric brain tumors include not
      only stereotactic biopsy but also stereotactic craniotomy, brachytherapy, and
      stereotactic radiosurgery. This paper illustrates the use of these techniques in
      brain tumors in children over a 2-year period at Children's Hospital, Boston.
      Stereotactic biopsy was used in six cases of deep-seated tumor, with successful
      tissue diagnosis in all six. Stereotactic craniotomy, in which excision of a mass
      was done in the stereotactic frame with computed tomography-guided localization
      and control, was employed in three children. Interstitial radiation using
      implanted 125I seeds was carried out in two children with malignant astrocytomas:
      in both it provided good local control but there was later distant recurrence.
      Stereotactic radiosurgery with a modified linear accelerator was used in eight
      children as adjunctive therapy for local control. These cases illustrate the
      versatility of stereotactic techniques involved in a comprehensive approach to
      pediatric brain tumors.

PMID- 8269419
TI  - Apnea associated with Chiari malformation: medullary hemorrhage revealed by MRI.
AB  - Medullary hemorrhage in the medulla oblongata of an infant with Chiari
      malformation, hydrocephalus, meningomyelocele and hypogenesis of the corpus
      callosum is reported. Four days after placement of a ventriculoperitoneal shunt,
      spontaneous respiration diminished. Magnetic resonance imaging (MRI) successfully
      revealed a small medullary hemorrhage.

PMID- 8269420
TI  - Reversible opisthotonus following intracranial pressure changes in Chiari
      malformation.
AB  - A shunted myelodysplastic child with Chiari II malformation presented with shunt
      malfunction and opisthotonus. Correction of a distal obstruction lead to an
      initial improvement followed by overdrainage of cerebrospinal fluid and
      repetition of an opisthotonic posture. The possible mechanisms which unmask lower
      brainstem dysfunction in Chiari malformation when intracranial hyper- or
      hypotension exist, are discussed.

PMID- 8269421
TI  - Pediatric interventional radiology: current practice and innovations.
AB  - The purpose of this article is to provide an update of pediatric interventional
      procedures for the interventionalist, and especially for those who treat children
      infrequently. Most pediatric interventional procedures are modifications of
      techniques devised for adults, in that some are unique to pediatrics. These are
      stressed in the presentation.

PMID- 8269422
TI  - Early sonographic evaluation of the transjugular intrahepatic portosystemic shunt
      (TIPS).
AB  - The purpose of this study was to evaluate duplex and color Doppler findings in
      patients before and within 24 h after transjugular intrahepatic portosystemic
      shunts (TIPS). Conventional duplex and color Doppler were used in the assessment
      of 19 patients who underwent TIPS as part of a prospective protocol. Patients
      were examined within 24 h before and after the procedure. Before TIPS, patency,
      flow direction, and peak flow velocity in the main portal vein and hepatic artery
      were studied, as well as patency and flow direction in hepatic veins, splenic
      vein, and inferior vena cava (IVC). Immediately after the procedure, sonographic
      identification of stent position, shunt patency, and flow dynamics were evaluated
      and patency and flow direction of hepatic veins, splenic vein, and IVC were
      determined. The portogram performed at the end of the procedure was compared with
      the 24-h sonographic studies after TIPS to determine sonographic/angiographic
      correlation. No intraparenchymal abnormalities or perihepatic fluid collections
      were detected after the procedure. The metallic stent was clearly seen in all
      patients. Mean peak shunt flow velocities were 139 +/- 50 cm/sec within 24 h
      after TIPS. Absence of flow through the shunt was correctly identified in one
      case and confirmed angiographically. Mean peak flow velocity in the portal vein
      before TIPS was 22 +/- 13.6 cm/sec and increased to 43.6 +/- 9.1 cm/sec after
      TIPS (p < 0.05). The hepatic artery peak systolic velocity increased from 77 +/-
      51 cm/sec before TIPS to 119 +/- 53 cm/sec after the procedure (p =
      0.029).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269423
TI  - Percutaneous penile venoablation for treatment of impotence.
AB  - Percutaneous penile venoablation with sclerosing agents and coils was performed
      in 58 patients. Of 104 ablations attempted, 44 of 51 (86%) transpenile, and 46 of
      53 (86.7%) retrograde interventions were technically successful. In 40 patients
      (69%) erectile function improved (intercourse was possible in 21 without
      additional measures). Initially improved erectile function deteriorated in 24
      patients during follow-up (in an average of 6 months); in 15 of these,
      intercourse was still possible with injection of vasoactive drugs. In 7 patients,
      repeat venoablation improved erectile function again. Hot contrast medium was
      slightly superior to sodium morrhuate as a sclerosing agent. In successfully
      treated patients, the average decrease in venous leakage was 30 ml/min vs 13
      ml/min in treatment failures, with considerable overlap between both groups. Only
      minor complications were observed. We conclude that percutaneous penile
      venoablation is technically feasible, and safe. Whether the procedure will have a
      definite role in the treatment of venogenic impotence, however, still has to be
      determined.

PMID- 8269424
TI  - Selective bilateral blood sampling from the inferior petrosal sinus in Cushing's
      disease: effects of corticotropin-releasing factor and thyrotropin-releasing
      hormone on pituitary secretion.
AB  - We sought to enhance the sensitivity of selective bilateral blood sampling to
      determine adrenocorticotropin (ACTH) and prolactin levels in the inferior
      petrosal sinus (IPS) by administering two stimulatory agents--corticotropin
      releasing factor (CRF) and thyrotropin-releasing hormone (TRH). We then
      determined the ACTH and prolactin levels in the IPS of 10 patients with Cushing's
      disease. After peripheral administration of both CRF and TRH, ACTH levels were
      significantly higher on the tumor side in all patients. The prolactin level was
      significantly higher on the tumor side when CRF or TRH was used to stimulate
      pituitary secretion. Postsurgical immunohistochemistry studies revealed
      production of both ACTH and prolactin in tumor cells, explaining the abnormal
      secretion pattern of the pituitary adenoma. The use of CRF and TRH may therefore
      improve the reliability of selective blood sampling and tests from the IPS in
      those cases of Cushing's disease for which noninvasive methods have otherwise
      failed to clarify the diagnosis.

PMID- 8269425
TI  - Radiological evaluation of the ascending aorta following repair of type A
      dissection.
AB  - A patient with persistent chronic dissection proximal to an aortic interposition
      graft for repair of a type A dissection prompted us to review the computed
      tomographic (CT) findings in 14 other such patients 5-47 months after surgery. No
      other case of proximal aortic dissection was identified although dilatation of
      the aortic root proximal to the graft was present in 8 patients (57%). Persistent
      dissection distal to the graft in 11 patients (79%) was in keeping with that
      reported by other workers. Chronic dissection proximal to the surgical repair of
      a dissection seems a rare although important complication.

PMID- 8269426
TI  - CO2 spray mini-injector for digital subtraction angiography versus PC-controlled
      injection system: experiments in dogs.
AB  - A personal computer (PC)-controlled CO2 injector (consisting of a pneumatic unit,
      electric/electronic system, and calculator) and a spray mini-injector (consisting
      of a CO2 spray can and a dosage chamber) were used in 10 dogs to determine their
      efficacy regarding imaging quality and ease of handling. CO2 was injected into
      the abdominal aorta, renal artery, and femoral artery. The vessel diameter was
      determined on each CO2 arteriogram and compared with that determined on a
      reference arteriogram obtained using an iodinated contrast agent. The filling
      ratio (CO2/iodine) was calculated for each set of injection parameters. Both
      injection systems provided good visualization (filling ratio > 0.9) of large and
      small arteries within a range of injection parameters. In terms of practicality,
      the spray mini-injector is more appealing, because it is easier to handle and
      does not require any preparation.

PMID- 8269427
TI  - Effectiveness and safety of ultrasonic atherosclerotic plaque ablation: in vitro
      investigation.
AB  - Ultrasound energy was applied to 137 segments of human cadaver atherosclerotic
      arteries, 90 with calcified and 47 with noncalcified atheromatous plaque, and to
      100 segments of healthy swine aorta. The average depth of penetration was
      dependent on the forward force of the ultrasonic probe, the duration of
      treatment, and the degree of atherosclerosis. There was one perforation of a
      fibrous plaque using a forward force of 2 Newton and 45 sec of application time.
      Injury of healthy intima was minimal. It is concluded that catheter-delivered
      ultrasound is effective and safe for the disintegration of atherosclerotic
      plaques. Presently, the main limitations of the system are the lack of
      flexibility and steerability.

PMID- 8269428
TI  - Monodisk: device for percutaneous transcatheter closure of cardiac septal
      defects.
AB  - The Monodisk, a device to facilitate percutaneous closure of cardiac septal
      defects, was developed and tested in vitro and in vivo. Atrial septal defects (8
      10 mm) were created in five dogs using transcatheter techniques. The defects were
      then closed with the Monodisk. The device was easily and successfully fixed in
      place in all dogs. The efficacy of the device was determined radiographically. No
      shunting of contrast medium was observed in any case. Animals were followed for 6
      months. Results showed good biocompatibility and several advantages of the
      device: it requires only a simple one-step placement procedure; it utilizes a
      small delivery system; it is easy to place and detach; it is self-centering and
      stable; and it can be repositioned or retrieved prior to detachment. Its possible
      clinical applications include correction of atrial septal defects, ventricular
      septal defects, patent ductus arteriosus, as well as creating an aortopulmonary
      window.

PMID- 8269429
TI  - Percutaneous transhepatic angioplasty and stent implantation for prehepatic
      portal vein obstruction.
AB  - Twenty-nine months after a Whipple procedure for pancreatic carcinoma, a 47-year
      old woman developed esophageal variceal bleeding. Percutaneous transhepatic
      portography revealed a severe stenosis of the portal vein with prehepatic portal
      hypertension and collateral circulation mainly to the gastric and esophageal
      veins. Percutaneous transhepatic balloon angioplasty was used to dilate the
      stenoses, but it did not remove the stenosis sufficiently. Therefore, an 8-mm,
      self-expandable stent was implanted, creating a nearly normal lumen without a
      pressure gradient. Portal hypertension was relieved, and the patient had no
      recurrent variceal bleeding for the 5 months up to her death.

PMID- 8269430
TI  - Transvenous Fogarty balloon catheter occlusion of an iatrogenic innominate artery
      to innominate vein fistula.
AB  - Transvenous embolization therapy is reported in a patient who developed a fistula
      from the innominate artery to the innominate vein as a complication of permanent
      cardiac pacemaker insertion. A transarterial approach at occlusion was
      unfavorable due to previous difficult catheterizations, and the patient's poor
      clinical condition precluded alternative operative intervention. The fistula was
      successfully closed by transvenous placement of a Fogarty nondetachable balloon
      catheter after coil and detectable balloon placement attempts were unsuccessful.

PMID- 8269431
TI  - Computed tomography diagnosis of partial anomalous pulmonary venous drainage.
AB  - A case of the rarely occurring partial anomalous pulmonary venous drainage of the
      right upper lobe into the azygos arch is presented. Computed tomography (CT)
      clearly demonstrated the abnormal vessel coursing through the right upper lobe
      and draining into the azygos arch.

PMID- 8269432
TI  - Percutaneous transcatheter treatment of an intracavitary aspergilloma.
AB  - We describe a case of massive hemoptysis, secondary to an intracavitary
      aspergilloma, successfully treated by computed tomography (CT)-guided placement
      of a Cope-loop catheter with daily transcatheter instillation of amphotericin B
      and cavitary irrigation. Over a 15-day period, this regimen resulted in cessation
      of hemoptysis and radiographic resolution of the aspergilloma. No complications
      were encountered. A follow-up CT of the thorax showed no recurrence of the
      aspergilloma at 3 months.

PMID- 8269433
TI  - Fatal septic complication of transcatheter chemoembolization for hepatocellular
      carcinoma.
AB  - A patient with hepatocellular carcinoma, associated segmental portal vein
      thrombosis, and accompanying pneumobilia, developed a liver abscess and sepsis
      following transcatheter chemoembolization (TCE). It was believed that the
      combination of bile duct necrosis after arterial occlusion and pneumobilia led to
      ascending enteric infection and seeding of the necrotic tumor, which ultimately
      led to fatal outcome. We conclude that TCE is contraindicated in such cases.

PMID- 8269434
TI  - Abdominal wall cellulitis and sepsis secondary to percutaneous cecostomy.
AB  - We report 1 case of abdominal wall cellulitis and sepsis which developed
      following percutaneous placement of a Cope catheter for cecal decompression in a
      patient with Ogilvie's syndrome. This case highlights that further laboratory
      investigation and clinical evaluation are needed to determine the safest and most
      efficacious technique of percutaneous drainage.

PMID- 8269435
TI  - Re: Aortocaval fistula demonstrated by computed tomography.

PMID- 8269436
TI  - Regimens for pediatric sedation.
AB  - Pediatric sedation is one of the most challenging areas of clinical practice. The
      goal of pediatric management is to accomplish treatment on a comfortable and
      cooperative child. While comfort may be achieved with or without drugs,
      cooperation may occasionally be achieved only when levels of sedation deepen to
      the point of obtunding the child. Anatomic and physiologic differences in the
      pediatric patient give high priority to airway management, oxygenation, and
      ventilation. Techniques for pediatric sedation and anesthesia are reviewed and
      recommendations are made for the rational selection of an appropriate
      pharmacological management technique.

PMID- 8269437
TI  - Local anesthetics in dentistry: clinical considerations, drug interactions, and
      novel formulations.
AB  - The pain control afforded by local anesthetics is the mainstay of dental
      practice. It is the medicolegal responsibility of all practicing dentists to
      possess a high level of expertise on the clinical use of these drugs. This
      article will discuss their clinical selection, recommended dosages, and new
      research developments that impact on dental medicine.

PMID- 8269438
TI  - Tooth sensitivity: mechanisms and management.
AB  - Tooth sensitivity is a common complaint encountered in clinical practice. Exposed
      superficial dentin is free of nerve endings, yet sensitive. Experimental evidence
      indicates that stimuli, such as probing the dentin surface and air blasts, induce
      fluid movements in the dentinal tubules and these fluid movements, in turn,
      activate the intradental nerves. The condition of the dentin surface is
      critically important in allowing this process. In addition, the internal
      environment of the pulp may influence nerve excitability. Therapies for tooth
      sensitivity include both agents that obstruct the dentinal tubules and agents
      that can decrease the excitability of the intradental nerves. The exact treatment
      used depends on the etiology of the individual's problem and the extent of
      dentinal tissue damage.

PMID- 8269439
TI  - Pentazocine analgesia: is there a niche for Talwin Nx?
AB  - Pentazocine can be a useful analgesic agent for the management of acute dental
      pain. It has both central and peripheral opioid activity. In clinical trials,
      analgesic compounds containing pentazocine have been shown to effectively relieve
      moderate-to-severe pain. It is an appropriate analgesic for the codeine-sensitive
      patient. Because of a change in formulation, the potential for abuse has been
      minimized. Although there is a possibility that the drug may have a
      psychotomimetic effect, the incidence is low and should not preclude use.
      Analgesic compounds containing pentazocine are clinically appropriate for the
      management of surgically induced dental pain.

PMID- 8269440
TI  - Infected health-care professionals: healers or modern day lepers? Part 2-
      Approaches and recommendations.

PMID- 8269441
TI  - Benzodiazepines for intravenous conscious sedation: agonists and antagonists.
AB  - Benzodiazepines, including diazepam and midazolam, have proved to be safe and
      effective for intravenous conscious sedation. Their selective anxiolytic activity
      and wide margin of safety contribute to their popularity. The recent introduction
      of the benzodiazepine receptor antagonist, flumazenil, provides flexibility and
      added safety for intravenous benzodiazepine sedation.

PMID- 8269442
TI  - The professionalization of dentistry--Part 1.

PMID- 8269443
TI  - Prevention of atherosclerosis in diabetes: emphasis on treatment for the abnormal
      lipoprotein metabolism of diabetes.
AB  - Atherosclerosis is the principal cause of diabetic morbidity and mortality.
      Diabetic dyslipidemia, obesity, and hypertension are significant contributing
      factors in the acceleration of the atherosclerotic process. Regardless of the
      type of diabetes, increased levels of very-low-density lipoprotein triglyceride,
      modified levels of low-density lipoprotein cholesterol, and decreased levels of
      high-density lipoprotein (HDL) cholesterol are the main lipoprotein abnormalities
      in diabetic patients. These abnormalities can be improved in part by glycemic
      control, but additional intervention may be needed. Diet and exercise are
      important elements in the management of dyslipidemia, but lipid-lowering drugs
      (especially fibrates and HMG-CoA reductase inhibitors) also may be necessary for
      the control of diabetic dyslipidemia. Based on these findings, the American
      Diabetes Association Consensus Panel and the revised treatment guidelines of the
      National Cholesterol Education Program recommend treatment of
      hypertriglyceridemia/low HDL cholesterol as a risk factor of coronary heart
      disease in diabetic and nondiabetic individuals alike. Aggressive treatment is
      recommended, therefore, particularly in diabetic patients and in all patients
      with existing vascular disease.

PMID- 8269444
TI  - Low-dose bisoprolol/hydrochlorothiazide: an option in first-line,
      antihypertensive treatment.
AB  - Two recent, multicenter, double-blind, placebo-controlled studies established the
      efficacy and safety of low-dose bisoprolol/hydrochlorothiazide (HCTZ) in patients
      with mild to moderate essential hypertension. Bisoprolol, a cardioselective beta
      blocker, was used in a dose of 2.5 mg, 5 mg, or 10 mg. HCTZ was used at a dose of
      6.25 mg. This low-dose compound was developed to minimize dose-related adverse
      effects. The addition of HCTZ to each of the doses of bisoprolol was compared
      with monotherapy and placebo. Results of both studies demonstrated that this once
      a-day, low-dose option effectively reduced sitting diastolic and systolic blood
      pressure measured at the end of the 24-hour dosing period. Drug-related adverse
      effects, including those generally associated with traditional beta-blocker
      therapy, were infrequent in individuals who received the low-dose bisoprolol/HCTZ
      regimen. Dose-related side effects were minimized because of the low doses of the
      two agents used together. There were no significant changes in mean total
      cholesterol, triglycerides, or serum glucose with bisoprolol/HCTZ 6.25 mg therapy
      versus placebo (analysis of variance statistical methods). The incidence of
      treatment-induced hypokalemia with bisoprolol/HCTZ 6.25 mg was not significant;
      uric acid elevations were minimized, and the incidence of hyperuricemia was
      significantly (P < 0.01) less with bisoprolol/HCTZ 6.25 mg than with 25 mg of
      HCTZ. Once-a-day dosing with the low-dose agent controlled (defined as a sitting
      diastolic blood pressure < or = 90 mmHg and/or a decrease from baseline > or = 10
      mmHg) blood pressure in up to 80% of patients for a full 24 hours after
      dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269446
TI  - Effect of zolpidem on sleep in healthy subjects: a placebo-controlled trial with
      polysomnographic recordings.
AB  - The aims of this double-blind, placebo-controlled study, conducted in a group of
      healthy young adults with normal sleep patterns, were to ascertain the effect of
      various doses of zolpidem on polysomnographic variables and to determine whether
      zolpidem disrupts sleep architecture. Of the 15 subjects recruited, 8 were
      included in the final analysis. Subjects underwent four experimental sessions
      during three nights, of which the first night was used for adaptation, the second
      for zolpidem (10, 20, and 40 mg) or placebo administration, and the third for
      placebo administration. Sleep was assessed by conventional sleep parameters
      (latency, duration, wakefulness) and by subjective questionnaire.
      Polysomnographic recordings were analyzed for sleep stage, paradoxical sleep,
      graphic features, and longitudinally with reference to sleep stage. Zolpidem had
      little effect on polysomnographic variables, except for a trend toward a hypnotic
      effect and a slight, transient inhibition of paradoxical sleep at the highest
      dose. In particular, the clearcut reduction of stage 4 sleep and increase in
      spindle density often observed with benzodiazepine administration was not
      observed with zolpidem. Adverse effects were restricted to three reports of
      daytime drowsiness each after zolpidem 10 and 40 mg and placebo, and one amnesic
      episode after the highest dose (40 mg). There were no signs of ataxic
      symptomatology.

PMID- 8269445
TI  - Efficacy and safety of reformulated, micronized glyburide tablets in patients
      with non-insulin-dependent diabetes mellitus: a multicenter, double-blind,
      randomized trial.
AB  - The subjects were 206 patients (123 men, 83 women) with non-insulin-dependent
      diabetes mellitus, aged 33 to 80 years. For at least 4 weeks prior to the study
      each subject had been taking 5-mg tablets of original, nonmicronized glyburide
      (Micronase tablets) in doses of 5, 10, 15, or 20 mg daily. In a double-blind 12
      week study, the subjects were randomly assigned to continue receiving 5-mg
      tablets of original glyburide or to substitute 3-mg tablets of reformulated,
      micronized glyburide (Glynase PresTab tablets) for the original tablets.
      Glyburide tablets had been reformulated to improve their bioavailability.
      Baseline mean fasting serum glucose levels in the groups taking reformulated and
      original glyburide were 169.3 and 168.3 mg/dl, respectively; at study end point,
      their respective serum glucose levels were 186.0 and 177.0 mg/dl. The differences
      between groups were not significant; in both groups, however, end point glucose
      levels were significantly higher than baseline levels. Baseline hemoglobin A1C
      levels in the groups taking reformulated and original glyburide were both 7.6%;
      at study end point, hemoglobin A1C levels had improved slightly in each group to
      7.4% and 7.5%, respectively. The differences between and within groups at end
      point were not significant. No between-group differences at baseline or at end
      point were found in mean levels of postprandial serum glucose, fasting C-peptide,
      or postprandial C-peptide. Medical events experienced by the subjects in the two
      groups were similar in nature and number. Changes in other laboratory test
      results, vital signs, and weight were not clinically meaningful.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269447
TI  - Large prospective study of ramipril in patients with hypertension. CARE
      Investigators.
AB  - The results of controlled trials demonstrate that ramipril lowers blood pressure
      in hypertensive patients, has a long duration of action suitable for once-daily
      administration in most patients, and is well tolerated. To assess the efficacy
      and safety of ramipril in a large cross-section of patients, we conducted a
      multicenter, open-label, prospective study, in which 591 men or women with
      essential hypertension (diastolic blood pressure > or = 95 and < or = 114 mmHg)
      received ramipril on a regimen of 1.25 to 10 mg once daily for 8 weeks. Forty-one
      percent of the patients required 2.5 mg and 81% required < or = 5 mg once daily
      at study completion. Compared with baseline, ramipril reduced mean
      systolic/diastolic blood pressure by 19.9/14.7 mmHg (P < 0.001/P < 0.001).
      Ramipril reduced diastolic blood pressure to < or = 90 mmHg or by at least 10
      mmHg in 84.1% of the patients. Response rates were similar regardless of age,
      gender, and race. No patient stopped ramipril because of an adverse event or
      experienced an unexpected adverse event. In our real-world study, low-dose
      ramipril given once daily controlled blood pressure in most patients and was well
      tolerated.

PMID- 8269448
TI  - Combination chemotherapy for infections due to methicillin-resistant
      Staphylococcus aureus with combination therapy by cefuzonam and fosfomycin or
      minocycline in the urologic field.
AB  - To determine the bacterial and clinical effects of methicillin-resistant
      Staphylococcus aureus (MRSA) on urinary tract infection (UTI), postoperative
      wound infection, and bacteremia, 22 strains of MRSA from infected patients were
      examined; minimal inhibitory concentration (MIC), fractional inhibitory
      concentration (FIC) index, coagulase typing, and change in MIC in the combination
      of cefuzonam (CZON) and fosfomycin (FOM) or minocycline (MINO), and the clinical
      effects of the combination therapy of CZON+FOM or CZON+MINO were investigated in
      23 patients. MIC distribution was assessed for 11 drugs: methicillin (DMPPC),
      cefazolin (CEZ), cefotiam (CTM), cefuzonam (CZON), minocycline (MINO), vancomycin
      (VCM), arbekacin (ABK), imipenem (IPM), fosfomycin (FOM), ofloxacin (OFLX), and
      clarithromycin (CAM). For VCM and ABK, MICs ranged from 0.2 to 12.5
      micrograms/ml. MINO showed a wide range of MIC, from 0.05 to 25 micrograms/ml.
      All strains were less sensitive to other antimicrobials. This MIC distribution
      was assessed in categories by coagulase typing. For CAM, type II strains revealed
      > or = 100 micrograms/ml of MIC50 and MIC90 compared with 0.2 and 3.13
      micrograms/ml in type VII strains. For mixed combinations of CZON and MINO at
      ratios of 10 to 1 and 40 to 1, the rates of blood concentration for drugs 10 and
      120 min after the intravenous injection, MIC distribution was observed between
      MINO and CZON. For mixed combinations of CZON and FOM at ratios of 1 to 1 and 1
      to 4, MIC distribution was more sensitive than for FOM or CZON alone. With
      respect to the clinical effects of combination therapy by CZON+MINO and CZON+FOM,
      of seven cases of UTI with CZON+MINO, MRSA was eliminated completely in 4
      patients (57.1%). In all patients who received CZON+FOM, MRSA was completely
      eliminated by this treatment regimen. In 4 of 7 (57.1%) patients with would
      infection and bacteremia, MRSA was eliminated by the combination of CZON+FOM or
      CZON+MINO. These results suggest that CZON+FOM is an effective combination in
      treating UTI and other MRSA infections in urology.

PMID- 8269449
TI  - Doxazosin improves insulin sensitivity in hypertensive patients.
AB  - Insulin sensitivity in terms of glucose disposal rate was measured by the
      hyperinsulinemic/euglycemic clamp technique in 10 hypertensive patients and 7
      normotensive control subjects before and after 12 weeks of doxazosin therapy.
      Supine blood pressure fell significantly, from 150/98 mmHg before treatment to
      136/90 mmHg after treatment (systolic P < 0.001/diastolic P < 0.01). The average
      dose of doxazosin at the end of the study was 3.3 +/- 0.4 mg/day. The glucose
      disposal rate during the last 30 minutes of the glucose clamp procedure was
      significantly increased, from 5.8 +/- 0.7 mg/kg/min before to 7.8 +/- 0.7
      mg/kg/min after treatment (P < 0.02). Insulin sensitivity was 8.7 +/- 0.4
      mg/kg/min in the normotensive subjects, which represented a significant
      difference when compared with that of the hypertensive subjects before treatment
      (P < 0.01). Steady-state serum insulin concentrations, as measured during the
      glucose clamp procedure, were 172 +/- 10.4 microU/ml before and 176 +/- 13.5
      microU/ml after doxazosin treatment; these levels were significantly higher than
      the 137 +/- 7.0 microU/ml reading obtained in the normotensive subjects (P <
      0.05). Study results show that hypertensive patients tend to be insulin resistant
      and that treatment with doxazosin improves insulin sensitivity.

PMID- 8269450
TI  - Effect of preinduction cervical softening with dinoprostone gel on outcome of
      oxytocin-induced labor.
AB  - Five hundred fourteen pregnant women at or near term with medically indicated
      inductions and unfavorable cervical induction features (Bishop score 0-4) were
      enrolled in an open-label randomized multicenter clinical trial to study the
      effect of endocervical administration of 0.5 mg of dinoprostone cervical gel as a
      preinduction cervical ripening agent. Patients in the treatment group (n = 265)
      received dinoprostone cervical gel 12 hours prior to oxytocin induction; patients
      in the control group (n = 249) were observed during this period. Thirteen
      patients in each group were excluded from efficacy evaluations. All patients were
      included in safety analysis. A mean Bishop score increase of 2.9 points was
      achieved in the treatment group, as compared with 0.6 point in the control group
      (P < 0.001). During the observation period, spontaneous labor occurred in a
      significantly greater percentage of patients in the treatment group (27%) than in
      the control group (2%). The percentage of patients who achieved labor either
      during the observation period or during the initial induction attempt was
      significantly larger in the dinoprostone cervical gel group (71.8%) than in the
      control group (54.2%). In addition, there was a statistically significant (P <
      0.001) difference in median induction-to-vaginal delivery time for the treatment
      group (10.6 hr) and the control group (13.0 hr). Side effects were reported for
      42% and 35% of patients in the treatment and control groups, respectively, with
      fetal heart rate abnormalities reported for approximately 27% of patients in each
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269451
TI  - A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in
      postoperative dental pain.
AB  - In a double-blind, parallel, placebo-controlled study, 203 patients with post
      operative dental pain following the extraction of one or two bony impacted third
      molars were randomized to receive a single dose of naproxen sodium 220 mg,
      ibuprofen 200 mg or placebo. Pain intensity and pain relief were assessed at
      intervals for 12 hours postdose. Both active drugs demonstrated superior
      analgesic efficacy over placebo. Naproxen sodium and ibuprofen were comparable
      both in onset of analgesic action and in pain relief. From 1 to 12 hours
      postdose, naproxen sodium showed a trend for superior analgesic efficacy compared
      with ibuprofen; this trend reached statistical significance at the 12-hour time
      point. Both drugs were well-tolerated and effective analgesics for postoperative
      dental pain.

PMID- 8269452
TI  - A comparative study of the efficacy and safety of loratadine syrup and
      terfenadine suspension in the treatment of 3- to 6-year-old children with
      seasonal allergic rhinitis.
AB  - The efficacy and safety of loratadine and terfenadine in the treatment of 3- to 6
      year-old children with seasonal allergic rhinitis were compared in a third-party
      blind, randomized, parallel-group study. A total of 96 children were included in
      the efficacy analysis: 49 children received 5 or 10 mg of loratadine once daily,
      and 47 received 15 mg of terfenadine twice daily, for 14 days. The mean total
      score for both nasal and non-nasal symptoms was decreased significantly from
      baseline at days 3, 7, and 14 in both treatment groups. At endpoint, these scores
      had improved 73% in each group. There were no statistically significant
      differences between the two groups in the total symptom scores at any point
      during the study. Both treatments were effective in relieving individual nasal
      and nonnasal symptoms. Therapeutic response to treatment was good or excellent in
      82% of loratadine-treated children and in 60% of terfenadine-treated children.
      Few adverse events were reported during the study; all were mild or moderate and
      were not significantly different between the two treatment groups. There were no
      reports of sedation or dry mouth in either group. Once-daily treatment with 5 or
      10 mg of loratadine was as effective as twice-daily treatment with 15 mg of
      terfenadine in improving the symptoms of seasonal allergic rhinitis in children 3
      to 6 years old. Both treatments were well tolerated.

PMID- 8269453
TI  - Inhibitory effect of ursodeoxycholic acid on the progression of chronic hepatic
      disorders with special reference to increases in blood flow.
AB  - Ursodeoxycholic acid (UDCA), which is commonly used as a cholesterol-gallstone
      dissolving agent, is now expected to be effective not only for primary biliary
      cirrhosis but for chronic active hepatitis as well. In this study, we
      administered 0.1% ethionine-added, choline-deficient diet for 8 weeks to male
      Sprague-Dawley rats to prepare an animal model of chronic hepatic disorders. At
      the same time, UDCA (50 mg/kg/day) was administered orally to these animals, and
      its effects on the liver, including effects on hepatic blood flow determined with
      a laser Doppler blood flow meter, were evaluated. Hepatic blood flow increased
      significantly in the UDCA group compared with the untreated groups. Transaminase
      levels decreased significantly in the UDCA group compared with the untreated
      group. Histologic differences were noted between the UDCA and untreated groups in
      histopathologic examinations of the liver, with liver cirrhosis or early liver
      cirrhosis being present in the untreated group, compared with only chronic active
      hepatitis in the UDCA group. These findings suggest that UDCA is able to prevent
      or inhibit the progression of chronic hepatic disorders, an effect that may be
      due in part to increases in hepatic blood flow.

PMID- 8269454
TI  - Comparison of in vitro susceptibilities of Bacteroides and Fusobacterium species
      in inland southern California to published patterns as a guide to empiric
      therapy.
AB  - Anaerobic bacteria, particularly the Bacteroides group, are becoming increasingly
      resistant to antimicrobials. Anaerobic susceptibility testing is often not done
      routinely in clinical laboratories, causing clinicians to depend on national
      survey results or susceptibility patterns published by different centers. In this
      study, we have determined anaerobic susceptibility patterns of 200 clinical
      isolates of anaerobic gram-negative bacilli from four hospitals in the inland
      countries of southern California (Inland Empire). Of 11 antibiotics tested,
      metronidazole and chloramphenicol were the most active, with no resistance noted,
      followed by imipenem, ticarcillin/clavulanate, and ampicillin/sulbactam. Among
      cephalosporins, cefoxitin was the most active and cefotetan the least.
      Significant differences in the susceptibility pattern to cefoxitin were observed
      in one hospital. Differences between our inland patterns and those for Los
      Angeles Wadsworth VA Hospital were seen for cefoxitin in the B fragilis group and
      piperacillin for B fragilis. We confirmed the National Committee for Clinical
      Laboratory Standards (NCCLS) recommendation for periodic determination of
      anaerobic susceptibility patterns. We also suggest that clinical laboratories
      routinely identify anaerobes to the species level to facilitate clinical
      application of in vitro results.

PMID- 8269455
TI  - Retention of carbon dioxide in tissue following carbonic anhydrase inhibition in
      dogs.
AB  - To evaluate the retention of carbon dioxide in tissue during the reduction of
      carbonic anhydrase activity following the administration of 5, 10, 20, or 30
      mg/kg of acetazolamide in dogs, we measured carbon dioxide pressure (PCO2) in
      arterial blood, mixed venous blood, alveoli, and tissue. Respiration was
      maintained at a constant level. In the control (noninjected) group, PCO2 in
      tissue did not change for 3 hours under controlled respiration. Following the
      injection of 5 to 30 mg/kg of acetazolamide, PCO2 increased in arterial blood,
      mixed venous blood, and tissue in a dose-related manner, and decreased in the
      alveoli. The (a-et)PCO2 widened to 21.9 +/- 1.0 mmHg from 0.6 +/- 1.0 mmHg, and
      the (t-v)PCO2 to 16.1 +/- 2.0 mmHg from 5.1 +/- 0.6 mmHg, in response to
      acetazolamide. It is suggested that carbon dioxide is retained in tissue when
      carbonic anhydrase activity is inhibited by acetazolamide.

PMID- 8269456
TI  - Experimental use of pravastatin in patients with primary biliary cirrhosis
      associated with hypercholesterolemia.
AB  - Primary biliary cirrhosis (PBC) is a refractory liver disease for which no
      medical treatment has been established. The investigators administered 20 mg/day
      of pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, to 2
      PBC patients with hypercholesterolemia (1010 and 306 mg/dl) for 3 years and 10
      months in order to decrease the blood concentration of bile acids and prevent
      adverse effects on the hepatocellular membrane. The drug markedly decreased not
      only cholesterol levels but also total bile acid levels, producing particularly
      pronounced decreases in cholic acid and chenodeoxycholic acid. Histologically,
      progression was inhibited in one patient, whereas improvement was seen in the
      other. Bile duct enzymes and other biochemical parameters showed improvement in
      both cases. General pruritus and blepharal and palmar xanthoma also improved.
      These findings suggest that pravastatin may be useful in the treatment of PBC
      associated with hypercholesterolemia.

PMID- 8269457
TI  - Drug utilization review using a Medicaid claims database.
AB  - A methodology for conducting drug utilization review (DUR) using Medicaid claims
      data is presented. The DUR allows for calculation of rates and costs of health
      care utilization among patients with established diagnoses and specific drug
      regimens; for comparison of results between competing drug therapies; for
      quantification of the percent market share of pharmaceutical products; and for
      projection of the duration of a given drug therapy. The strengths and limitations
      of using Medicaid data for DUR are discussed.

PMID- 8269458
TI  - Effect of pharmaceutical formulation for diltiazem on health care expenditures
      for hypertension.
AB  - A 1-year retrospective analysis was undertaken to discern the economic utility of
      providing prescription coverage for the sustained-release (SR) formulation of
      diltiazem, a calcium-channel antagonist, under the state of South Carolina's
      Medicaid program. Data for this analysis were derived from the state of South
      Carolina's Medicaid computer archive. The study population consisted of 347
      ambulatory beneficiaries diagnosed with hypertension for whom either the SR or
      immediate-release (IR) formulation of diltiazem was prescribed. Multivariate
      regression analysis was used to discern the incremental influence of selected
      demographic characteristics, use of medical services prior to diagnosis for
      hypertension, and prescribed formulation of diltiazem on health care expenditures
      1-year postdiagnosis. Patients for whom the SR formulation of diltiazem was
      prescribed achieved a significant (P < or = 0.05) increase in the medication
      possession ratio, an index of compliance (SR, 0.63 +/- 0.17) relative to patients
      for whom the IR formulation was prescribed (IR, 0.44 +/- 0.13). Results indicate
      that receipt of diltiazem in an SR formulation was associated with a significant
      decrease in aggregate health care expenditures over the 1-year study period
      ($258.80, P < or = 0.05). Receipt of the SR formulation was associated with an
      increase in expenditures for antihypertensive therapy ($109.26, P < or = 0.05),
      and a decrease in financial commitments for physician ($128.70, P < or = 0.05),
      hospital ($211.84, P < or = 0.05), and laboratory ($27.52, NS) services. At the
      managerial and policy levels, these data argue for an increased use of
      therapeutic alternatives that facilitate a reduction in the patient's daily
      dosing schedule for antihypertensive therapy.

PMID- 8269459
TI  - Medication costs associated with the care of HIV-infected patients.
AB  - The treatment costs for human immunodeficiency virus (HIV)-infected patients
      continue to rise as patients survive longer because of advances in antiretroviral
      therapy and effective chemoprophylaxis. Medication costs per patient increase in
      proportion to progressive immunodeficiency. We retrospectively studied medication
      costs for 196 HIV-infected patients with stratification by CD4-lymphocyte count.
      Medication costs per patient-month were correlated with CD4-lymphocyte count
      (linear regression, r = -.53, P < 0.01), with higher costs associated with lower
      CD4 counts. The medication cost for patients with CD4 counts < 100 cells/mm3
      averaged $1043 per month. Medication costs per patient increase with the
      development of each new opportunistic infection or other AIDS-associated
      condition. Costs can be expected to increase as new therapeutic agents are
      introduced, as treatment is initiated at earlier stages of HIV infection, and as
      more patients survive to the point of severe CD4-lymphocyte depletion.

PMID- 8269460
TI  - Economic assessment of ketorolac versus narcotic analgesics in postoperative pain
      management.
AB  - The medical records for 174 patients who underwent cholecystectomy (n = 52) or
      hip/knee replacement (n = 122) at four community-based medical centers were
      retrospectively reviewed to determine if using a nonnarcotic alternative to
      morphine sulfate and/or meperidine as a primary postoperative analgesic could
      reduce resource costs per patient. Two cohorts were constructed: 87 patients
      received either morphine sulfate or meperidine as the primary postoperative
      analgesic, and 87 patients received ketorolac. Ketorolac patients undergoing
      cholecystectomy were associated with lower per case costs in inpatient care
      (length of stay), direct nursing labor, PRN (as required) procedures, and
      medications relating to emesis and to gastrointestinal distress. Higher per case
      costs were recorded for the primary analgesic (study drug) and for supplemental
      pain medications. In contrast to substantial differences in the acquisition cost
      of ketorolac versus morphine sulfate/meperidine, the ketorolac cholecystectomy
      group was associated with lower overall resource costs per patient. In joint
      replacement procedures, however, the ketorolac group was associated with higher
      overall resource costs per patient, attributable primarily to a slightly higher
      postoperative length of stay.

PMID- 8269461
TI  - [The Bayesian statistical theory in the diagnosis of malignant and non-malignant
      diseases of the lung, pleura and mediastinum].
AB  - The Bayesian algorithm was used to assess the probable diagnosis in 1262 patients
      with a recently diagnosed finding on X-rays of the chest and the results were
      compared with the final diagnosis. The patients were with regard to the X-ray
      picture divided into 9 groups: hilar, solitary, multiple, segmental, non
      segmental, cavity, diffuse, pleural and mediastinal lesions. Using the Bayesian
      algorithm, commonly accessible factors were processed: age, sex, case-history,
      cigarette smoking, red cell sedimentation rate, number of leucocytes and diameter
      of solitary parenchymatous lesions and the impact of these factors for assessment
      of probability of a malignant or non-malignant lesion was evaluated. The
      reliability in different X-ray lesions was within the range of 84.2% to 92.4%.
      The authors evaluated also tests of sensitivity, specificity, the reliability of
      forecast of a positive and negative result, which confirmed the differences in
      the different groups which showed evaluated. Analysis of the results, provided
      evidence that the Bayesian algorithm is a promising objective method for the
      forecast of a malignant or non-malignant diagnosis in patients with a newly
      diagnosed X-ray finding of the chest.

PMID- 8269462
TI  - [The bronchodilator agent, Ventodisk, in the powdered inhalation form without
      freon is better].
AB  - The authors compared the effectiveness and advantages of the powdered inhalation
      variety of the preparation Ventodisc (Glaxo) with the "classical" dosed
      inhalation form of Salbutamol (Polfa) in 21 patients with bronchial asthma.
      During administration of 0.2 mg of the two drugs various conditions (mastering of
      the inhalation technique, elimination of the action of other drugs and the same
      time of day when the drug was administered) was respected. Values of ventilation
      parameters of the central and peripheral respiratory pathways before
      administration of the drugs did not differ significantly. The powdered form of
      salbutamol--Ventodisc (Glaxo) had a greater dilatating action than the classical
      dosed aerosol form--Salbutamol (Polfa) because: 1. in FEV1 values between rest
      and Ventodisc (1.47 l and 1.73 l) differed significantly, however, after
      subsequent inhalation of Salbutamol no further significant improvement occurred
      (1.79 l); 2. when the sequence of stimuli was reversed a significant increase of
      the FEV1; value occurred after Salbutamol (from 1.50 l to 1.67 l, p < 0.004) but
      Ventodisc caused a further significant increase (p < 0.0006). The tolerance of
      both drugs was equal. The powdered inhalation form of Salbutamol (Ventodisc-
      Glaxo) was better than the "classical" dosed aerosol form of salbutamol
      (Salbutamol--Polfa) as it had a greater dilatating effect in the central airways
      and moreover did not contaminate the environment.

PMID- 8269463
TI  - [The dead space in volitional changes in respiratory volume].
AB  - The objective of the investigation was to assess changes of the dead space under
      conditions of volitional changes of the respiratory volume. The authors assessed
      therefore in repeated experiments in 11 healthy volunteers basic respiratory
      variables and the effective dead space using a Mijnhardt spirometer at rest and
      during cortically conditioned changes of the tidal volume. When the breath
      deepens the effective dead space reaches higher absolute values, but the relative
      values decline. When the breathing is more shallow, the reverse occurs. Thus e.
      g. in men of the investigated group a mean value of the respiratory volume at
      rest was assessed which amounted to 0.74 +/- 0.10 l, the relative dead space
      declined to 19 +/- 7%, when breathing was shallow it rose to 37 +/- 10%.

PMID- 8269464
TI  - [Changing from spontaneous to volitional regulation of respiration decreases
      dyspnea].
AB  - The objective of the investigation was to assess whether volitional control of
      respiration can influence the intensity of dyspnoea. In 17 volunteers the author
      assessed, using Borg's method, the intensity of dyspnoea during breathing with an
      added dead space of 600 ml and with a flow resistance. The experiments were made
      in two sessions. During the first session when the examined subjects breathed
      spontaneously the author recorded spirographically the respiratory volume during
      control ventilation and after inclusion of the dead space and resistance. During
      the second session the experimental subjects were asked to attempt to imitate
      during inclusion of the dead space and resistance, as closely as possible, the
      respiratory pattern from the first session. In both instances the author assessed
      the partial pressure of CO2 in the air at the end of the expiration (P(ET)CO2).
      During the first session the tested subjects evaluance the dyspnoea: it had an
      average grade of 5.9 +/- 1.9. Volitional regulation of breathing led not only to
      a significant decline of the sensation of dyspnoea to 3.4 +/- 1.5 points of
      Borg's scale but also to a decline of the CO2 partial pressure (on average by 0.4
      kPa). The author selected therefore among the tested subjects only those who were
      able to imitate closely the respiratory pattern from the first session (they had
      the same P(ET)CO2 in both instances). Also in these 8 subjects the intensity of
      dyspnoea during volitional control of ventilation declined from 6.5 +/- 1.8 grade
      to 3.8 +/- 1.5 grade according to Borg. The change from spontaneous to volitional
      regulation of breathing thus reduced the intensity of dyspnoea.

PMID- 8269465
TI  - [Microbiological study of patients with enterocutaneous fistulae treated with
      long-term total parenteral nutrition].
AB  - The authors followed up 12 patients with dehiscences of surgical wounds and
      postoperative enterocutaneous fistulas treated by on a long-term basis by
      complete parenteral nutrition. Previous operations were performed on account of
      different non-tumorous (11/12) and tumourous (1/12) diseases of the
      gastrointestinal tract. Microbiological examinations were made in every patient
      on admission and during total parenteral nutrition, always once a week for a
      total period of 2-8 weeks (mean 4.4; median 4.5). The authors examined aerobic
      and facultatively anaerobic bacteria in smears from the fistulas, stomies,
      dehiscent surgical wounds and from the rectum. The findings did not confirm the
      suspicion of local nosocomial infection. Strikingly often bacteria producing
      indole were found (in 8/12 examined subjects) and/or bacteria with positive
      urease (12/12) and lecithinase activity (9/12 patients). In the detected strains
      of Pseudomonas aeruginosa (in 8/12 examined patients) lecithinase activity was
      confirmed in all. It cannot be ruled out that the above described enzymatic
      bacterial activities may have contributed to the failure of conservative therapy
      in the majority of patients (10/12).

PMID- 8269466
TI  - [Therapy with fibrates and vitamin D metabolism].
AB  - The authors investigated in 29 patients with familial hyperlipoproteinaemia the
      effect of fibrate treatment (Duolip forte, Merckle, and Lipanthyl, Richter) on
      vitamin D metabolism. In 10 patients treated for 6 months with daily oral doses
      of 500 mg Duolip forte they did not prove changes of plasma levels of 25
      hydroxyvitamin D, however, they recorded a rise of the 1,25-dihydroxyvitamin D3
      plasma level. In 19 patients who were given for 6 months 300 mg Lipanthyl per day
      by the oral route they proved a significant decline of the 25-hydroxyvitamin D
      plasma levels and a rise of 1,25-dihydroxyvitamin D3 plasma levels. The authors
      maintain that fibrates influence plasma concentrations of vitamin D metabolites
      either directly or indirectly by reducing cholesterol plasma levels.

PMID- 8269467
TI  - [Pulmonary alveolar microlithiasis].
AB  - The authors present two of their own observations where, based on the clinical
      course of the disease and the X-ray finding, they diagnosed the condition as
      pulmonary alveolar microlithiasis. They present a review of the literature as
      regards new views on the pathogenesis, diagnosis and therapy of the condition.
      They evaluate the contribution of scintigraphy 99 mTc, bronchial lavage and X-ray
      methods with a high differentiating capacity (HRCT). As regards therapeutic
      possibilities, transplantation of the lungs should be considered in advanced
      stages of the disease.

PMID- 8269468
TI  - [Popper's critical rationalism and the biomedical sciences].
AB  - Popper's rationalism makes an important contribution of the 20th century
      philosophy to the methodology of natural sciences. Through its criterion of
      falsification, it enabled the scientists to take a critical but constructive view
      on hypotheses, conjectures and theories. This attitude found its application also
      in medicine.

PMID- 8269469
TI  - [Energy requirements for walking].
AB  - The energy requirement of walking, expressed indirectly by the oxygen consumption
      per kg body weight was assessed during different speeds of walking on a treadmill
      within the range of 3-12 km.h-1 in 87 untrained healthy men aged 17.5 to 60
      years. The dependence of VO2.kg-1 on the speed of walking is non-linear in the
      mentioned range. Most suitable is the two-component linear model which in the
      range of 3-7 km.h-1 has the shape of VO2.kg-1 (ml.kg-1.min-1 = 3.207.v/km.h-1 -
      1.777, r = 0.932 with a mean predicting error of 1.5.ml.kg-1.min-1, in the range
      of load of 7-12 km.h-1 VO2 = 7.120.v - 29.168, r = 0.941 with a error predicting
      of 3.73. The polynomic model of relations in the entire range of 3-12 km.h-1 is
      VO2 = 4.503 - 0.108.v + 0.379.v2, r = 0.922 with a predicting error of 4.43 ml.kg
      1.min-1, and finally the exponential model has the shape VO2 = 4.360 exp
      (0.223.v), r = 0.861 with a mean predicting error of 6.84 ml.kg-1.min-1 in the
      entire range of load intensities. The justification to express the relationship
      between the oxygen consumption and the rate of walking by a two-component linear
      model as well as by non-linear models is confirmed also by the high correlation
      coefficient (p < 0.001 in all instances). The error of assessment of VO2.kg-1
      from the speed of walking is 10% or less in all models. The mentioned models, in
      particular the linear one, can be used for evaluation of physical activities
      involving walking outdoors.

PMID- 8269470
TI  - [Treatment of glioblastoma multiforme].
AB  - The authors evaluate therapeutic results in 31 patients with the diagnosis of
      multiform glioblastoma. The comprehensive therapeutic procedure used as a rule
      which involves surgery, radiotherapy and in some instances also chemotherapy
      still gives very unsatisfactory results. The mean survival period of patients
      after surgery was 26.7 weeks and the mortality of patients within one month was
      22.6%. Even radical surgery does not produce more favourable therapeutic results.
      Contemporary trends of preclinical and clinical research are focused in
      particular on different immunotherapeutic methods.

PMID- 8269471
TI  - [The effect of aminophylline on the sinoatrial node].
AB  - The objective of the submitted prospective study was to assess the influence of
      intravenously administered aminophylline on the sinoatrial node. The authors
      examined by electrophysiological methods 20 patients (16 without dysfunction of
      the sinoatrial node and 4 with dysfunction of the sinoatrial node). From the
      investigation patients were eliminated with an apparent and obvious cause of
      elevated uric acid serum levels and patients where on electrophysiological
      examination limited values of the corrected recovery time of the sinoatrial node
      were found (from 650 ms to 999 ms). To all 20 patients 240 mg aminophylline were
      administered by the i.v. route with in 2 mins. The following parameters were
      recorded: age, serum level of uric acid, basal heart rate in ms, corrected
      recovery time of the sinoatrial node in ms, heart rate and corrected recovery
      time of the sinoatrial node 5 min after completed administration of aminohpylline
      in ms. As regards age and uric acid serum levels there was no significant
      difference between dysfunction of the sinoatrial node and normal function of the
      sinoatrial node. Intravenously administered aminophylline hastened significantly
      the heart rate in patients without dysfunction of the sinoatrial node (p < 0.05).
      The value of the corrected recovery time of the sinoatrial node was shorter but
      the difference was not statistically significant. In patients with dysfunction of
      the sinoatrial node aminophylline did not affect the heart rate and corrected
      recovery time of the sinoatrial node.

PMID- 8269472
TI  - [The Museum of Medicine begins a new life].

PMID- 8269473
TI  - [The past and future of the Czech Pharmaceutical Society].

PMID- 8269474
TI  - Fine-structural localization of proenkephalin mRNAs in the hypothalamic
      magnocellular dorsal nucleus of the guinea pig: a comparison of radioisotopic and
      enzymatic in situ hybridization methods at the light- and electron-microscopic
      levels.
AB  - With the aim of localizing proenkephalin mRNAs in neurons of the hypothalamic
      magnocellular dorsal nucleus of the guinea pig, we compared the in situ
      hybridization signals obtained on Vibratome sections with a method employing
      either a biotinylated or a digoxigenin-labeled oligonucleotide detected by means
      of the alkaline phosphatase reaction. Since the hybridization approach using the
      biotinylated probe was more sensitive than the digoxigenin method, the
      ultrastructural localization of hybrids in neurons of the magnocellular dorsal
      nucleus was studied by the use of the former procedure, and was further compared
      with results of in situ hybridization using a 35S-labeled probe. Biotin was
      detected via an amplified avidin-biotin-peroxidase complex. Radioactive hybrids
      were localized over extended cytoplasmic compartments rich in rough endoplasmic
      reticulum and also in nuclear indentations. The method based on biotinylated
      probe proved to be sensitive and provided high-resolution labeling in well
      preserved specimens. Proenkephalin mRNAs were clearly localized within
      circumscribed cytoplasmic compartments. The immunoprecipitates were mainly
      observed within the rough endoplasmic reticulum, especially at the periphery of
      the cell. The reticulum was dominated by elongated parallel cisternae. The
      labeling also appeared in a paranuclear position, mainly in nuclear indentations.
      The labeling was found on the outer surface of the endoplasmic lamellae. The
      remainder of the reticulum was unlabeled. Neuronal processes were free of
      labeling.

PMID- 8269475
TI  - Occurrence, distribution and possible role of the regulatory peptide endothelin
      in the nasal mucosa.
AB  - Nasal blood flow is finely regulated by local release of neurotransmitters,
      neuropeptides and other bioactive molecules acting via paracrine mechanisms. We
      have investigated the occurrence and distribution in human nasal mucosa of
      endothelin, a potent vasoconstrictor peptide, by immunocytochemistry and the
      effect of systemic administration of endothelin-1 on vascular perfusion of rabbit
      nasal mucosa by laser Doppler flowmetry. Endothelin-like immunoreactivity was
      demonstrated within vascular endothelial cells in both developing and mature
      human mucosa. Nasal epithelial cells and some connective tissue cells, presumed
      to be macrophages, also displayed specific immunostaining. In rabbits injected
      with endothelin-1, a potent and prolonged nasal vasoconstriction was observed. It
      is suggested that endothelin released locally may participate in the regulation
      of nasal blood flow via paracrine mechanisms. Since endothelin has growth
      promoting actions on several cell types, it is also tentatively proposed that
      this regulatory peptide may play a role during development of the nose.

PMID- 8269476
TI  - Immunohistochemical localization of a gap junction protein (connexin43) in the
      muscularis externa of murine, canine, and human intestine.
AB  - Electron-microscopic studies have revealed a heterogeneous distribution of gap
      junctions in the muscularis externa of mammalian intestines. This heterogeneity
      is observed at four different levels: among species; between small and large
      intestines; between longitudinal and circular muscle layers; and between
      subdivisions of the circular muscle layer. We correlated results obtained with
      two immunomethods, using an antibody to the known gap-junctional protein
      (connexin43) with ultrastructural findings, and further evaluated the respective
      sensitivity of these two approaches. For comparative reasons we also included the
      vascular smooth muscle of coronary arteries into our study. Two versions of the
      immunotechnique (peroxidase-antiperoxidase and fluorescence methods) were applied
      to frozen sections of murine, canine, and human small and large intestines, as
      well as to pig coronary artery. In the small intestine of all three species a
      very strong reactivity marked the outer main division of the circular muscle
      layer, while the longitudinal muscle layer as well as the inner thin division of
      the circular muscle layer were negative. In murine and human colon both muscle
      layers were negative, while in canine colon the border layer between the circular
      muscle and the submucosa reacted strongly, and scattered activity was found in
      the portion of the circular muscle layer (one tenth of its thickness) closest to
      the submucosa. The remainder of the circular muscle layer and the entire
      longitudinal muscle layer were negative in the canine colon. In the coronary
      artery we could not confirm the positive, specific labeling reported by other
      investigators (l.c.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269477
TI  - Immuno-electron-microscopic localization of enkephalin in the secretory granules
      of C cells in the chicken ultimobranchial glands.
AB  - In the chicken, enkephalin-immunoreactive cells and nerve fibers are distributed
      in the ultimobranchial glands, which consist of C-cell groups and cyst
      structures. Ultrastructural features of the enkephalin cells and nerve fibers
      were examined by immuno-electron microscopy using both the streptavidin-biotin
      peroxidase method and the protein A-colloidal gold method. Immunoreactivity for
      enkephalin was located on the secretory granules of C cells. In 1-day-old
      chickens, three types of C cells were distinguished on the basis of their granule
      size. Type-I cells were filled with large secretory granules (200-600 nm in
      diameter). These elements represented a majority of the C-cell population. Type
      II cells contained medium-sized granules (100-280 nm in diameter). Type-III cells
      displayed small secretory granules (60-200 nm in diameter). The latter cells were
      elongate or irregular in shape and frequently extended cytoplasmic processes into
      the connective tissue stroma or contacted other C cells. Enkephalin
      immunoactivity was revealed by dense deposits of immunogold particles on the
      secretory granules of type-II and type-III cells. There were only a few type-I
      cells showing immunoreactivity for enkephalin. A double immunogold labeling
      procedure demonstrated that calcitonin and enkephalin were colocalized in the
      same secretory granules of type-I and type-II cells. Type-III cells were devoid
      of immunoreactivity for calcitonin. Enkephalin-immunoreactive nerve fibers were
      characterized by the presence of granular vesicles, 60-160 nm in diameter, and
      frequently established direct contact with the surface of C cells.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269478
TI  - Immunohistochemical localization of GABAA receptors in the scotopic pathway of
      the cat retina.
AB  - The distribution of GABAA receptors in the inner plexiform layer of cat retina
      was studied using monoclonal antibodies against the beta 2/beta 3 subunits. A
      dense band of receptor labeling was found in the inner region of the inner
      plexiform layer where the rod bipolar axons terminate. Three forms of evidence
      indicate that the GABAA receptor labeling is on the indoleamine-accumulating,
      GABAergic amacrine cell that is synaptically interconnected with the rod bipolar
      cell terminal. (1) Electron microscopy showed that the anti-GABAA receptor
      antibody (62-3G1) labeled profiles that were postsynaptic to rod bipolar axons
      and made reciprocal synapses. (2) Indoleamine uptake (and the subsequent
      autofluorescence) combined with GABAA receptor immunohistochemistry showed co
      localization of the two markers in half of the receptor-positive amacrine cells.
      (3) Double labeling demonstrated that half of the receptor-positive somata also
      contained GABA. These results indicate that a GABAergic amacrine cell
      interconnected with the rod bipolar cell, most likely the so-called A17 amacrine
      cell, itself bears GABAA receptors.

PMID- 8269479
TI  - Structure-activity relationships in corpora allata of the cockroach Diploptera
      punctata: roles of mating and the ovary.
AB  - Morphometric studies were made on corpora allata of the cockroach Diploptera
      punctata from animals in which increasing gland size is not coupled to hormone
      synthesis (ovariectomized mated females; last-instar larvae) and in which gland
      size is coupled to hormone synthesis (normal mated and virgin females;
      penultimate-instar larvae). Cell number, gland volume, and juvenile hormone
      synthesis were measured. From electron micrographs, nuclear, cytoplasmic, and
      extracellular volumes; and cell membrane area were calculated; and fine structure
      described. Low-activity glands of ovariectomized mated females resembled high
      activity glands from mated females in high cell number, large overall and
      cytoplasmic volume, and low nuclear-cytoplasmic ratio; they differed in having
      organelles typical of low-activity glands, mitochondria with dense matrices and
      large whorls of smooth endoplasmic reticulum. Inactive last-instar larval glands
      resembled mated ovariectomized female glands in increased cell number and
      organelles characteristic of inactive glands; however, their nuclear-cytoplasmic
      volume ratio was much higher. Penultimate larval glands with high activity per
      cell resembled active glands of normal mated females. Ovariectomy did not change
      morphometric parameters of virgin female glands; thus mating results in increase
      in size of adult female glands whereas the growing ovary is needed for changes in
      mitochondria and endoplasmic reticulum associated with high juvenile hormone
      synthesis.

PMID- 8269480
TI  - Postnatal development of intra-epithelial leukocytes in the chicken digestive
      tract: phenotypical characterization in situ.
AB  - In the present study, we characterized intra-epithelial leukocytes in the
      digestive tract of chickens during postnatal development. Their phenotype was
      characterized by monoclonal antibodies in cryostat sections and the numbers of
      the different cell-types were counted in the epithelium of the esophagus,
      proventriculus, duodenum, jejunum, cecum, and colon. All intra-epithelial
      leukocytes bore the leukocyte-common antigen CD45; 35% were T lymphocytes, and
      50% bore a B-cell marker. However, no immunoglobulin-bearing cells were detected
      in the epithelium. Monocytes and macrophages were found only in the epithelium of
      the esophagus. A remaining population of non-B, non-T, non-monocyte cells (15%)
      was present in all parts of the digestive tract. The number of intra-epithelial
      leukocytes was greatest in the duodenum and jejunum, and decreased in the
      proximal part of the cecum and in the colon. Intra-epithelial leukocytes were
      only sporadically detected in the proventriculus. The total number of intra
      epithelial leukocytes increased until 8 weeks after hatching and then decreased
      at 18 months. In the esophagus, the total number of intra-epithelial leukocytes
      changed little during aging. We found that the intra-epithelial leukocytes of
      chickens and rodents are distinct in that chicken intra-epithelial leukocytes
      comprise a cell population that bears a B-cell antigen but that lacks surface
      immunoglobulins.

PMID- 8269482
TI  - Attempts to label matrix synthesis of human root cementum in vitro.
AB  - The present study describes the dynamic process of both acellular extrinsic
      (AEFC) and acellular/cellular intrinsic fiber cementum (AIFC/CIFC) matrix
      production on growing human teeth. Selected erupting maxillary and mandibular
      premolars with roots grown to about 70%-95% of their final length were placed in
      organ culture immediately following extraction. Twelve teeth for short-time
      labeling were pulse-incubated for 15 min in medium containing 3H-proline and
      chased for various times in order to follow the migration and secretion of the
      tracer. Eight teeth for long-time incubation were labeled continuously for 5 h
      before being chased for 1-8 days in order to label cementum matrix accumulation.
      After decalcification in ethylene diaminetetraacetic acid (EDTA), their roots
      were subdivided into about 20 slices each. Epon-embedded sections were prepared
      for light- and electron-microscopic as well as autoradiographic examination.
      During CIFC-formation, cementoblasts revealed high intracytoplasmic silver grain
      concentrations within the first hour after 3H-proline administration. The release
      of the tracer occurred between 60 to 120 min after administration. After 2 h,
      cementoblasts and the cementum matrix appeared to be labeled about equally. After
      5 h, most of the labeled proteins appeared to be localized in the cementoid.
      Silver grains increased in number over the cementum matrix from 5-24 h. Very high
      intracellular grain concentrations within very large cementoblasts corresponded
      to regions of rapid cementum formation. Tracer-halos around entrapped cells lend
      support to a multipolar mode of matrix production during CIFC-initiation. The
      fate of the tracer during the development of early AEFC-matrix was less clear.
      However, fibroblasts revealed dense intracytoplasmic grain accumulations within
      the first hour after 3H-proline administration. Thereafter, the tracer
      localization was vague. This indistinct grain localization reflected the
      particular mode of AEFC-matrix production characterized by addition of new fibril
      segments to pre-existing fibers of a collagenous fringe.

PMID- 8269481
TI  - Lack of effect of oxytocin on the numbers of "synaptic" ribbons, cyclic guanosine
      monophosphate and serotonin N-acetyltransferase activity in organ-cultured
      pineals of three strains of rats.
AB  - In addition to the stimulating influence of the sympathetic system on the
      function of the mammalian pineal gland, neuropeptides such as neuropeptide Y,
      vasoactive intestinal polypeptide and arginine-vasopressin (AVP) are thought to
      function as modulators. Since AVP has been shown to influence pineal melatonin
      synthesis, the aim of the present study was to investigate the possible effects
      of the second hypothalamic nonapeptide oxytocin (OT), which likewise has been
      detected in the pineal gland. We therefore studied "synaptic" ribbon (SR)
      numbers, N-acetyltransferase (NAT) activity and the intracellular concentration
      of cyclic guanosine monophosphate (cGMP) following in vitro incubation of rat
      pineals in media containing OT (10(-5) M), noradrenaline (NA, 10(-5) M) or both
      NA and OT. Pineal glands were derived from rats of three different strains
      (Sprague-Dawley, Long-Evans and the AVP-deficient strain Brattleboro). Neither
      morphological nor biochemical analyses showed a difference between control and OT
      incubated organs in any of the strains tested. In Brattleboro rats, but not in
      the other strains, noradrenaline slightly increased the number of SR which was
      not observed when NA and OT were combined. The addition of NA resulted in
      distinct augmentation of NAT activity and cGMP content, which were not affected
      by additional OT application. These results suggest that oxytocin is not
      crucially involved in the regulation of pineal gland function.

PMID- 8269483
TI  - Ultrastructure of Kolmer's crystalloid in the pinealocytes of the common spiny
      mouse (Acomys cahirinus dimidiatus).
AB  - Light- and electron-microscopical observations revealed a rod-like inclusion body
      in the pinealocytes of the common spiny mouse (Acomys cahirinus dimidiatus).
      Ultrastructurally, the body is composed of a varying number of tubes whose wall
      consists of thin filaments aligned in helical arrangement. The inner and outer
      surface of the wall is covered with ribosome-like granules. Based on a
      morphological analysis it is concluded that the body described in the present
      investigation is identical with Kolmer's crystalloid of horizontal cells in the
      human and primate retina.

PMID- 8269484
TI  - Development of chicken intrafusal muscle fibers.
AB  - The first sign of developing intrafusal fibers in chicken leg muscles appeared on
      embryonic day (E) 13 when sensory axons contacted undifferentiated myotubes. In
      sections incubated with monoclonal antibodies against myosin heavy chains (MHC)
      diverse immunostaining was observed within the developing intrafusal fiber
      bundle. Large primary intrafusal myotubes immunostained moderately to strongly
      for embryonic and neonatal MHC, but they were unreactive or reacted only weakly
      with antibodies against slow MHC. Smaller, secondary intrafusal myotubes reacted
      only weakly to moderately for embryonic and neonatal MHC, but 1-2 days after
      their formation they reacted strongly for slow and slow-tonic MHC. In contrast to
      mammals, slow-tonic MHC was also observed in extrafusal fibers. Intrafusal fibers
      derived from primary myotubes acquired fast MHC and retained at least a moderate
      level of embryonic MHC. On the other hand, intrafusal fibers developing from
      secondary myotubes lost the embryonic and neonatal isoforms prior to hatching and
      became slow. Based on relative amounts of embryonic, neonatal and slow MHC future
      fast and slow intrafusal fibers could be first identified at E14. At the polar
      regions of intrafusal fibers positions of nerve endings and acetylcholinesterase
      activity were seen to match as early as E16. Approximately equal numbers of slow
      and fast intrafusal fibers formed prenatally; however, in postnatal muscle
      spindles fast fibers were usually in the majority, suggesting that some fibers
      transformed from slow to fast.

PMID- 8269485
TI  - Ferritin accumulation and uroporphyrin crystal formation in hepatocytes of
      C57BL/10 mice: a time-course study.
AB  - To establish the time-sequence relationship between ferritin accumulation and
      uroporphyrin crystal formation in livers of C57BL/10 mice, a biochemical,
      morphological and morphometrical study was performed. Uroporphyria was induced by
      the intraperitoneal administration of hexachlorobenzene plus iron dextran and of
      iron dextran alone. Uroporphyrin crystal formation started in hepatocytes of mice
      treated with hexachlorobenzene plus iron dextran at 2 weeks and in mice treated
      with iron dextran alone a 9 weeks. In the course of time, uroporphyrin crystals
      gradually increased in size. Uroporphyrin crystals were initially formed in
      hepatocytes in the periportal areas of the liver, in which also ferric iron
      staining was first detected. The amount and the distribution of the main storage
      form of iron in hepatocytes, ferritin, did not differ between the two treatment
      groups. Ferritin accumulation preceded the formation of uroporphyrin crystals in
      hepatocytes in both treatment groups. Moreover, uroporphyrin crystals were nearly
      always found close to ferritin iron. We conclude that uroporphyrin crystals are
      only formed in hepatocytes in which also iron (ferritin) accumulates.
      Hexachlorobenzene accelerates the effects of iron in porphyrin metabolism, but
      does not influence the accumulation of iron into the liver.

PMID- 8269486
TI  - The effect of rate of eruption on periodontal ligament glycosylaminoglycan
      content and enamel formation in the rat incisor.
AB  - The rate of eruption of rat mandibular incisors was either increased by cutting
      one tooth out of occlusion or eliminated by means of pinning. The effects of such
      changes in eruption rate on the sulphated glycosylaminoglycan content of the
      periodontal ligaments was analysed. The length of the enamel secretory zone and
      the composition of the developing enamel matrix protein was also compared.
      Sulphated glycosylaminoglycan content of the periodontal ligament increased
      fourfold (P < 0.001) during accelerated eruption but decreased to a corresponding
      extent (P < 0.001) in the absence of eruption, when compared with controls. The
      length of the enamel secretory zone was also significantly reduced in the
      immobilised teeth, although the protein content was similar compared with
      controls. The results demonstrate the differential response to varied eruption
      rates of the periodontal ligament and enamel, particularly in respect of the
      extracellular matrix. The data are consistent with the view that the ground
      substance of the periodontal ligament plays a role in the generation of the
      eruptive force.

PMID- 8269487
TI  - Multivariable model for prediction of risk of significant complication during
      diagnostic cardiac catheterization. The Registry Committee of the Society for
      Cardiac Angiography & Interventions.
AB  - Although adequate data exist on the frequency of procedural-related complications
      during diagnostic cardiac catheterization, little information is available for
      the quantitative assessment of risk factors for significant complication. We
      analyzed 58,332 procedures in the 1990 SCA&I Registry Database in order to assess
      1) the independent and cumulative significance of easily obtainable pre
      procedural factors predictive of major complication and 2) the likelihood of a
      significant complication given the presence of these risk factors. A model was
      developed on a random sample of 38,888 patients and validated in the remaining
      19,444 patients. Twelve variables were identified as having independent
      predictive behavior for significant complication with excellent agreement in the
      validation sample. The current model is an accurate and reliable instrument for
      stratifying risk of a significant complication during diagnostic catheterization.

PMID- 8269488
TI  - Guidelines for continuous quality improvement in the cardiac catheterization
      laboratory. Laboratory Performance Standards Committee of the Society for Cardiac
      Angiography & Interventions.
AB  - The Laboratory Performance Standards Committee of the Society for Cardiac
      Angiography and Interventions has compiled guidelines for a quality improvement
      program for the cardiac catheterization laboratory. The first step is to identify
      "quality indicators" in order to quantify the results. The indicators must be
      risk-adjusted to assure validity of comparative data. The second step is
      development of a data collection process that continues after the patient has
      left the catheterization laboratory. The third step, data evaluation, requires
      determination of normal ranges of occurrence rates and identification of adverse
      events that exceed these rates. An investigation should be undertaken to
      determine the processes and systems that may produce the undesirable outcome. The
      fourth step is creation of a solution to correct the deficiency. This may involve
      education, administrative intervention, or feedback. The final step is
      reassessment of the quality indicators to determine if the corrective action has
      been effective.

PMID- 8269489
TI  - Glidewire treatment of resistant coronary occlusions.
AB  - Inability to cross the site of occlusion with a guidewire is the most common
      cause of failed angioplasty. The Glidewire, a kink-resistant, flexible wire with
      a hydrophilic coating, was applied to 71 (59 total, 12 subtotal) refractory
      occlusions, resulting in an overall angioplasty success rate of 45%. The
      Glidewire may improve the success rate for PTCA of total and subtotal occlusions
      that cannot be crossed with conventional guidewires.

PMID- 8269490
TI  - Holmium: YAG laser-assisted coronary angioplasty with multifiber delivery
      catheters.
AB  - Mid-infrared lasers are attractive for coronary angioplasty based upon their
      excellent fiberoptic transmission and enhanced tissue absorption. Using a solid
      state, mid-infrared holmium:YAG laser with prototype multifiber laser delivery
      catheters, we performed coronary laser angioplasty with or without adjunctive
      balloon angioplasty or directional atherectomy in 14 patients with 17 stenoses.
      Procedural laser success was obtained in 13/14 (93%) patients and 16/17 (94%)
      lesions; however clinical success was achieved in 9/14 (64%) patients and 12/17
      (71%) stenoses. Angiographic restenosis at 4.6 +/- 1.6 months was found in 5/8
      (63%) patients. We achieved an excellent procedural laser success rate in
      patients with generally unfavorable angioplasty anatomy. However, our clinical
      success rate was not different from that expected with conventional angioplasty
      alone. The holmium laser remains an attractive energy source for laser
      angioplasty; but as is the case for all coronary laser systems, its utility as a
      stand-alone therapy is limited by catheters which create small channels. In this
      small group, we could demonstrate no clinical benefit for laser-assisted
      angioplasty in complex coronary lesions. Our results suggest that a randomized
      trial comparing laser-assisted angioplasty and conventional angioplasty be
      performed to determine the clinical benefits of this more expensive therapy.

PMID- 8269491
TI  - Total aortic occlusion caused by sustained balloon inflation: a previously
      unreported complication of intraaortic balloon counterpulsation.
AB  - A case of acute lower-body ischemia 2 days following intraaortic balloon pump
      insertion is reported. Fluoroscopy revealed persistent balloon inflation
      throughout the cardiac cycle with distal aortic occlusion. Attempts to manually
      deflate the balloon were unsuccessful until a guidewire was advanced through the
      gas-exchange lumen into the body of the balloon. The balloon catheter was removed
      without clinical sequelae other than transient oliguria and an asymptomatic
      increase in creatinine phosphokinase (CPK). This is a previously unreported
      complication of intraaortic balloon counterpulsation.

PMID- 8269492
TI  - Acute occlusion of a remote coronary artery complicating directional coronary
      atherectomy.
AB  - Two cases of acute occlusion in a remote coronary artery complicating directional
      coronary atherectomy are reported. In neither case was there definite
      angiographic evidence of spasm, dissection, or embolization. Since this
      complication is seldom seen with coronary angioplasty, it may represent a
      relatively specific risk of directional atherectomy.

PMID- 8269493
TI  - Contralateral femoral vein removal of a circumferentially ruptured balloon
      catheter following pulmonary artery angioplasty.
AB  - While attempting to remove a circumferentially ruptured balloon following branch
      pulmonary artery angioplasty, the shaft of the catheter broke, leaving the distal
      portion of the balloon and catheter in the femoral vein but still on the exchange
      wire. We describe a method to retrieve the broken balloon catheter via the
      contralateral femoral vein.

PMID- 8269494
TI  - Deep venous thrombosis and pulmonary embolism following cardiac catheterization.
AB  - We report 4 cases of deep venous thrombosis and/or pulmonary embolism after
      diagnostic cardiac catheterization. Two of these cases followed left heart
      catheterization alone.

PMID- 8269495
TI  - Emergency coronary stenting for acute occlusive dissection of the left main
      coronary artery.
AB  - Catheter-induced left main coronary artery dissection is a rare but serious
      complication of diagnostic cardiac angiography. We report the case of a patient
      with mitral regurgitation and accidental dissection of the left main coronary
      artery successfully managed with intracoronary stent that allowed emergent
      surgical revascularization and mitral replacement.

PMID- 8269496
TI  - Diagnosis of left atrial myxoma at routine coronary angiography in an
      asymptomatic patient.
AB  - Asymptomatic atrial myxomas are very rare and are usually diagnosed at
      echocardiography. Abnormal left atrial vascularity was seen as an incidental
      finding in an asymptomatic patient at coronary angiography. Transesophageal
      echocardiography revealed a large left atrial mass and a left atrial myxoma was
      removed at surgery. The patient remains well.

PMID- 8269497
TI  - Right coronary angiography: optimal utilization of sagittally angulated views.

PMID- 8269498
TI  - Retrieval of undeployed stents from the right coronary artery: report of two
      cases.
AB  - Two patients are described in whom an undeployed stent (1 Wiktor and 1 Palmaz
      Schatz) was retained in the proximal segment of the right coronary artery during
      coronary angioplasty. In both cases the stent was caught by a technique using a
      second guidewire. The stent was removed in the first patient during bypass
      surgery; in the second patient it was removed from the femoral sheath.

PMID- 8269499
TI  - Adaptor device for shortening guide catheters to access distal lesions in
      coronary angioplasty.
AB  - One of the challenges in interventional cardiology is accessing distal stenoses
      in both native coronary arteries and bypass grafts. This article reports the
      fabrication and use of an adaptor device that can be connected to the proximal
      segment of a shortened guide catheter for easier and safer access to these distal
      lesions.

PMID- 8269500
TI  - Experience with U-shaped catheters in angiography and angioplasty of the left
      coronary artery.
AB  - We developed a U-shaped diagnostic and guiding catheter for left coronary
      angiography and angioplasty. Angiography with a 6 French (F) diagnostic U-shaped
      catheter was attempted in 101 patients (pts). Primary use in 82 pts; all
      successful. Secondary use after failure of 6 F left Judkins diagnostic catheters
      to intubate the left main coronary artery in 19 pts; 17 successful. An 8 F U
      shaped guiding catheter was used for percutaneous transluminal coronary
      angioplasty (PTCA) of left coronary artery branches in 102 pts [left anterior
      descending (LAD), 48 pts; circumflex (CX), 54 pts]. Stable cannulation of the
      left coronary artery was achieved in 96 pts (94%), but PTCA was successful in 90
      pts (88%). Primary use in 70 pts (LAD, 27 pts; CX, 43 pts). PTCA was successful
      in 60 pts. Secondary use after failure of left Judkins and Amplatz guiding
      catheters in 32 pts (LAD, 21 pts; CX, 11 pts). PTCA was successful in 30 pts. No
      complications were seen. In conclusion, U-shaped diagnostic and guiding catheters
      increased the success rate of 1) left coronary angiography after failure of left
      Judkins diagnostic catheters; and 2) PTCA of the left anterior descending and
      circumflex arteries after failure of left Judkins and Amplatz guiding catheters.

PMID- 8269501
TI  - Variations in acoustical beam properties of intracoronary Doppler catheters.
AB  - The limitations of coronary angiography in assessing the functional significance
      of coronary obstructions is well known. While the critical variable of coronary
      blood flow cannot be readily measured, intraluminal Doppler sonography offers
      useful related functional information on blood flow velocity. In order to fully
      evaluate Doppler signals it is essential to have exact knowledge of the
      transducer transmission characteristics and of the ultrasound beam topology. In
      an experimental set-up, the transmitter-receiver characteristics of five commonly
      used Doppler catheters were investigated. In comparing the beam characteristics
      we found inhomogeneities in the lateral beam spread. At a penetration depth of
      3.0 mm the beam shape varied from a minimum of 1.25 mm up to a maximum of 3.5 mm.
      The mean was 2.25 mm. The different beam profiles of the investigated Doppler
      transducers cause an error in measuring the blood flow velocity. The blood flow
      velocity tends to be underestimated the more the vessel diameter and the blood
      flow velocity increase. Contrary to transducer design optimized for imaging, for
      spectral analysis of the Doppler signal it would be advantageous to have as broad
      a beam as possible in order to illuminate the entire vessel lumen.

PMID- 8269502
TI  - Translesional flow velocity for lesion assessment.

PMID- 8269503
TI  - Balloon rupture complication.

PMID- 8269504
TI  - More on ACT.

PMID- 8269505
TI  - Mutations in G protein-linked receptors: novel insights on disease.

PMID- 8269506
TI  - The MyoD family and myogenesis: redundancy, networks, and thresholds.

PMID- 8269507
TI  - Notch: neurogenesis is only part of the picture.

PMID- 8269508
TI  - The riddle of morphogenesis: a question of solution chemistry or molecular cell
      engineering?

PMID- 8269509
TI  - Modified hippocampal long-term potentiation in PKC gamma-mutant mice.
AB  - Calcium-phospholipid-dependent protein kinase (PKC) has long been suggested to
      play an important role in modulating synaptic efficacy. We have created a strain
      of mice that lacks the gamma subtype of PKC to evaluate the significance of this
      brain-specific PKC isozyme in synaptic plasticity. Mutant mice are viable,
      develop normally, and have synaptic transmission that is indistinguishable from
      wild-type mice. Long-term potentiation (LTP), however, is greatly diminished in
      mutant animals, while two other forms of synaptic plasticity, long-term
      depression and paired-pulse facilitation, are normal. Surprisingly, when tetanus
      to evoke LTP was preceded by a low frequency stimulation, mutant animals
      displayed apparently normal LTP. We propose that PKC gamma is not part of the
      molecular machinery that produces LTP but is a key regulatory component.

PMID- 8269510
TI  - PKC gamma mutant mice exhibit mild deficits in spatial and contextual learning.
AB  - We are undertaking a genetic approach to investigate the role that synaptic
      modulation in the mammalian central nervous system plays in learning and memory
      and to identify relevant molecular components. We have generated mice deficient
      in the gamma isoform of protein kinase C (PKC gamma), an enzyme that has
      previously been implicated in both long-term potentiation (LTP) and learning and
      memory. These mice have a modified LTP of synaptic transmission in the
      hippocampus. We demonstrate that PKC gamma-mutant mice can learn to carry out
      hippocampus-dependent tasks, although mild deficits are evident. Thus,
      hippocampal CA1 LTP induced by the conventional tetanic stimulation is not
      essential for the mice to exhibit spatial and contextual learning. Furthermore,
      the modification of hippocampal synaptic plasticity correlates with the learning
      deficits we observe.

PMID- 8269511
TI  - A Y chromosome gene family with RNA-binding protein homology: candidates for the
      azoospermia factor AZF controlling human spermatogenesis.
AB  - We have previously mapped the human azoospermia factor to a deletion in Y
      chromosome interval 6 (subinterval XII-XIV). We now report the isolation and
      characterization of a gene family located within this deletion. Analysis of the
      predicted protein products suggests a possible role in RNA processing or
      translational control during early spermatogenesis. The Y chromosome RNA
      recognition motif (YRRM) family includes a minimum of three members expressed
      specifically in the testis. Interphase in situ results and Southern blot analysis
      indicate that several further YRRM sequences map within interval 6. Several
      mammalian species show Y chromosome conservation of YRRM sequences. We have
      detected deletions of YRRM sequences in two oligospermic patients with no
      previously detectable mutation.

PMID- 8269512
TI  - Identification and characterization of the tuberous sclerosis gene on chromosome
      16.
AB  - Tuberous sclerosis (TSC) is an autosomal dominant multisystem disorder with loci
      assigned to chromosomes 9 and 16. Using pulsed-field gel electrophoresis (PFGE),
      we identified five TSC-associated deletions at 16p13.3. These were mapped to a
      120 kb region that was cloned in cosmids and from which four genes were isolated.
      One gene, designated TSC2, was interrupted by all five PFGE deletions, and closer
      examination revealed several intragenic mutations, including one de novo
      deletion. In this case, Northern blot analysis identified a shortened transcript,
      while reduced expression was observed in another TSC family, confirming TSC2 as
      the chromosome 16 TSC gene. The 5.5 kb TSC2 transcript is widely expressed, and
      its protein product, tuberin, has a region of homology to the GTPase-activating
      protein GAP3.

PMID- 8269513
TI  - MyoD or Myf-5 is required for the formation of skeletal muscle.
AB  - Mice carrying null mutations in the myogenic regulatory factors Myf-5 or MyoD
      have apparently normal skeletal muscle. To address whether these two factors
      functionally substitute for one another in myogenesis, mice carrying mutant Myf-5
      and MyoD genes were interbred. While mice lacking both MyoD and Myf-5 were born
      alive, they were immobile and died soon after birth. Northern blot and S1
      nuclease analyses indicated that Myf-5(-1-);MyoD(-1-) mice expressed no
      detectable skeletal muscle-specific mRNAs. Histological examination of these mice
      revealed a complete absence of skeletal muscle. Immunohistochemical analysis
      indicated an absence of desmin-expressing myoblast-like cells. These observations
      suggest that either Myf-5 or MyoD is required for the determination of skeletal
      myoblasts, their propagation, or both during embryonic development and indicate
      that these factors play, at least in part, functionally redundant roles in
      myogenesis.

PMID- 8269514
TI  - RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure
      determines position and efficiency.
AB  - A functionally critical position (Q/R site) of the AMPA receptor subunit GluR-B
      is controlled by RNA editing that operates in the nucleus, since in brain and
      clonal cell lines of neural origin, unspliced GluR-B transcripts occur edited in
      the Q/R site CAG codon and, additionally, in intronic adenosines. Transfection of
      GluR-B gene constructs into PC12 cells revealed that the proximal part of the
      intron downstream of the unedited exonic site is required for Q/R site editing.
      This intron portion contains an imperfect inverted repeat preceding a 10 nt
      sequence with exact complementarity to the exon centered on the unedited codon.
      Single nucleotide substitutions in this short intronic sequence or its exonic
      complement curtailed Q/R site editing, which was recovered by restoring
      complementarity in the respective partner strand. Base conversion in the channel
      coding region of GluR-B directed by base paired sequences may be executed by a
      ubiquitous nuclear adenosine deaminase specific for double-stranded RNA.

PMID- 8269515
TI  - In vitro protein splicing of purified precursor and the identification of a
      branched intermediate.
AB  - Protein splicing is a posttranslational processing event in which an internal
      polypeptide is excised from a protein precursor and the terminal polypeptides are
      then ligated together, resulting in the production of two proteins. This report
      presents direct evidence for protein splicing by demonstrating in vitro splicing
      of purified precursor that accumulated when the protein splicing element from
      Pyrococcus DNA polymerase was cloned into a foreign gene. In vitro splicing was
      temperature and pH dependent. A slowly migrating species exhibited kinetic
      properties of a splicing intermediate and was shown to be a branched molecule by
      N-terminal sequencing. The precursor and slowly migrating species were
      interconvertible in response to pH shifts.

PMID- 8269516
TI  - Dual roles of a multiprotein complex from S. cerevisiae in transcription and DNA
      repair.
AB  - Yeast RNA polymerase II initiation factor b, homolog of human TFIIH, is a protein
      kinase capable of phosphorylating the C-terminal repeat domain of the polymerase;
      it possesses a DNA-dependent ATPase activity as well. The 85 kd and 50 kd
      subunits of factor b are now identified as RAD3 and SSL1 proteins, respectively;
      both are known to be involved in DNA repair. Factor b interacts specifically with
      another DNA repair protein, SSL2. The ATPase activity of factor b may be due
      entirely to that associated with a helicase function of RAD3. Factor b
      transcriptional activity was unaffected, however, by amino acid substitution at a
      conserved residue in the RAD3 nucleotide-binding domain, suggesting that the
      ATPase/helicase function is not required for transcription. These results
      identify factor b as a core repairosome, which may be responsible for the
      preferential repair of actively transcribed genes in eukaryotes.

PMID- 8269517
TI  - The semaphorin genes encode a family of transmembrane and secreted growth cone
      guidance molecules.
AB  - In addition to its expression on subsets of axons, grasshopper Semaphorin I (Sema
      I, previously called Fasciclin [Fas] IV) is expressed on an epithelial stripe in
      the limb bud, where it functions in the guidance of two sensory growth cones as
      they abruptly turn upon encountering this sema I boundary. We report here on the
      cloning and characterization of two sema genes in Drosophila, one in human, and
      the identification of two related viral sequences, all of which encode proteins
      with conserved Semaphorin domains. Drosophila sema (D-Sema) I is a transmembrane
      protein, while D-Sema II and human Sema III are putative secreted proteins that
      are similar to the recently reported chick collapsin. D-Sema I and D-Sema II are
      expressed by subsets of neurons and muscles. Genetic analysis in Drosophila
      reveals that semall is an essential gene that is required for both proper adult
      behavior and survival.

PMID- 8269518
TI  - Sonic hedgehog mediates the polarizing activity of the ZPA.
AB  - The zone of polarizing activity (ZPA) is a region at the posterior margin of the
      limb bud that induces mirror-image duplications when grafted to the anterior of a
      second limb. We have isolated a vertebrate gene, Sonic hedgehog, related to the
      Drosophila segment polarity gene hedgehog, which is expressed specifically in the
      ZPA and in other regions of the embryo, that is capable of polarizing limbs in
      grafting experiments. Retinoic acid, which can convert anterior limb bud tissue
      into tissue with polarizing activity, concomitantly induces Sonic hedgehog
      expression in the anterior limb bud. Implanting cells that express Sonic hedgehog
      into anterior limb buds is sufficient to cause ZPA-like limb duplications. Like
      the ZPA, Sonic hedgehog expression leads to the activation of Hox genes. Sonic
      hedgehog thus appears to function as the signal for antero-posterior patterning
      in the limb.

PMID- 8269519
TI  - A functionally conserved homolog of the Drosophila segment polarity gene hh is
      expressed in tissues with polarizing activity in zebrafish embryos.
AB  - The segment polarity gene hedgehog (hh) encodes a novel signaling protein that
      mediates local cell-cell interactions in the developing Drosophila embryo. Here
      we describe the existence of an hh-related gene family in the zebrafish,
      Brachydanio rerio. One of these genes, sonic hedgehog (shh), is expressed in the
      notochord, floor plate, and posterior fin mesoderm, tissues associated with
      polarizing activities in various vertebrate embryos. The pattern of shh
      expression in zebra-fish mutants affecting axial structures, together with the
      consequences of its ectopic expression in normal embryos, is consistent with a
      role for shh in floor plate induction. By expressing shh in transgenic Drosophila
      embryos, we also demonstrate a strong functional conservation between the fish
      and fly hh genes.

PMID- 8269520
TI  - [Early onset schizophrenia (case report)].
AB  - A total of 120 children and adolescents with the diagnosis of schizophrenia were
      hospitalized at the psychiatric clinic in Prague in 1946-1975. Of the 120
      patients (58% males and 42% females) 12.5%, i.e. 15 died by 1988. The results are
      consistent with data in the literature which pertain to pregnancy, family
      background, relations with people already before the disease developed, social
      maladaptation, more frequent loss of a parent, depressive symptoms at the onset
      of the disease, changes on the EEG and neurological examination. The results
      differ as regards--1. A much greater hereditary load in grade II relatives 45%
      (19% psychoses, 14% suicides, 12% alcoholism). 2. A greater hereditary load in
      grade I relatives-parents and siblings (16% psychoses and suicides, 5%
      alcoholism, 12% personality disorders). 3. The authors detected more psychoses
      among grade I relatives 14% (11% schizophrenia, 3% manic-depressive psychosis).
      The hereditary load in the narrower sense of the word in grade I relatives is
      significantly elevated 16% (14.5% psychoses, 1.5% suicides). Based on the results
      pertaining to the 15-42-year catamnestic investigation of education, occupation,
      attempts to work, a certain socialization, attacks and remissions, the authors
      elaborated the prognosis. The author's prognosis of early onset schizophrenia:
      10% complete cure, 17% remission alternating with relapses, 73% chronic patients
      (20% are capable of a certain socialization; in 53% permanent care by another
      person is necessary-this applies to chronic patients with a defect-deterioratio
      and postpsychotic psychopathization.

PMID- 8269521
TI  - [The effect of cocaine on binding of tricyclic antidepressives in the synaptic
      plasma membranes in the brain].
AB  - Effect of cocaine on binding of 3H-imipramine, 3H-desmethylimipramine, 3H
      didesmethylimipramine and 3H-amitriptyline to brain synaptic plasma membranes
      (SPM) was studied. Binding of methylated tricyclic antidepressants was more
      affected. Cocaine inhibits 3H-imipramine binding at concentrations higher than
      10(-5) mol/l. Binding stimulated by phosphatidylserine was affected more
      significantly.

PMID- 8269522
TI  - [Neuropsychological tests and smooth pursuit eye movements in schizophrenic
      twins].
AB  - The authors compares results of neuropsychological tests/Halstead-Reitan
      Neuropsychological Battery, Stroop test, Wechsler Memory Scale, Seashore Tonal
      Memory Test/with results of smooth pursuit eye movements in nine pairs of twins/5
      monozygotic and 4 dizygotic pairs/. In all instances at least one twin suffered
      from schizophrenia. The majority of neuropsychological tests differentiated
      clearly schizophrenic and healthy twins. Of seven parameters of smooth pursuit
      eye movements big saccades differentiated significantly. The authors found also
      correlations between neuropsychological tests and smooth pursuit eye movements.
      Significant correlations pertained to motor velocity (correlation of the
      Oscillation test with big saccades and with small saccades), complex psychomotor
      abilities (correlation of the Tactual Performance Test-Localization with big
      saccades), general indicators of cerebral activity or neuropsychological
      performance (correlation of the Tonal Memory test with big saccades and
      correlation of the Rhythm test with the amplitude of the curve), memory
      (correlation of the memory quotient MQ and the Logical Memory sub-test with small
      saccades) and work performance during a perception or psychic load (correlation
      of Stroop sub-test with big saccades). The method of smooth pursuit eye movements
      is not time consuming and does not involve major demands on the patient's
      cooperation. On the other hand, neuropsychological tests have the advantage that
      they reveal the impact of possible pathological conditions of the brain on
      behaviour. On the whole the results support the hypothesis that in schizophrenic
      patients a disease with structural or functional abnormalities of the brain is
      involved.

PMID- 8269523
TI  - [Forensic psychiatric diagnoses and assessment of abnormal psychosocial
      development].
AB  - Introduction of the concept of severely abnormal personality development in the
      legal code in the former GDR in 1968 (section 16, para 1) made acquittal of
      criminals possible where abnormal psychosocial development was proved. So far,
      however, statistically based criteria for the classification of this legal
      decision were lacking. The authors compared, using statistical methods, severely
      pathological abnormal personality development and a group of subject homogenized
      on the basis of substantial parameters. Mainly due to multivariance methods they
      were able to visualize different syndromes which are characterized by the given
      criteria of severely abnormal personality development.

PMID- 8269524
TI  - [The duration of female orgasm].
AB  - Short orgasm lasting from 3 to 15 second was for a long time viewed as the only
      regularly occurring type of female orgastic experience. Bohlen et al. (1992) and
      other authors demonstrated in physiological experiments the occurrence of a
      longer female orgasm of the duration between 20 seconds and 2 minutes. Hubalek
      and Raboch (1984) found in structured interviews with marital couples that such
      long female orgasms were not exceptional. About 40% of 121 women estimated the
      duration of their orgasm to be 30 to 60 seconds or even longer, mostly in
      agreement with independent estimates of their husbands. Our own findings are
      based on our sexuological inventory SGZ, which contains one open question
      concerning the duration of respondent's orgasm. In a sample of 200 women treated
      for neurosis 37% reported long orgasm, 37% short orgasm and 26% did not answer
      the question. In a sample of 100 female health professionals and counselors, 48%
      experienced predominantly long orgasm and 44% short ones (8% did not answer). Our
      data confirm relatively frequent occurrence of long orgasm in females.

PMID- 8269525
TI  - [The theoretical basis of "process-oriented psychotherapy"].
AB  - Process-oriented psychotherapy /POP/ is an eclectic trend. It is based on Jungian
      psychology but is inspired also by some dynamic schools and oriental philosophy,
      in particular Taoism. The essence of the psychotherapeutic method is work with
      signals in the communication channels. By their reinforcement the personality
      attains contact with the secondary process behind the borderline of identity. In
      addition to psychopathological indications it uses somatic symptoms and diseases
      which are considered a purposeful message of the dream body.

PMID- 8269526
TI  - [Problems in mandatory sex therapy].
AB  - The authors focus attention on analysis of advantages and problems of the Czech
      model of imposed treatment of criminal sexual deviants. Relatively favourable
      therapeutic results are in their opinion due above all to the very good standard
      of sexuological diagnosis, the theoretical background of the Czech sexuological
      school, to comprehensive therapeutic action, incl. the continuous character of in
      and out-patients treatment. Unfavourable features are in their opinion lack of
      uniformity as regards indications for institutional treatment, gradual abolition
      or restriction of sexuological departments and the persisting admission of
      incurable, dangerous delinquents to mental sanatoria and the non-existence of
      special detention institutes for criminal recidivists.

PMID- 8269527
TI  - [The stereotype of the mentally ill].
AB  - The objective of the submitted work was to obtain a more accurate picture of lay
      ideas on mentally ill people in seven selected population groups--two classes
      from a school for health workers, two classes of general secondary schools,
      participants of a training course for nurses organized by the church, employees
      of the law court and prosecution and patients of a psychiatric hospital/a total
      of 181 respondents. The respondents were asked to give at least 5 expressions
      characterizing a mentally sick person or lunatic. A total of 948 statements,
      incl. 450 different ones, were obtained. The statements were divided into four
      categories, depending whether they expressed a favourable or unfavourable
      quality, the need of assistance, protection or sympathy or whether they were
      neutral. The author assessed the ratio of categories by groups of respondents,
      repeatedly used expressions and qualities described in the statements. With the
      exception of the from of pupils of an extension course for health workers, where
      the majority were statements expressing the need of assistance, in the remaining
      groups more than half the expressions were unfavourable, in five the difference
      was statistically significant. The difference between students from the school
      for health workers and students from general secondary schools was significant
      only as regards the number of favourable replies from those in the extension
      course the difference was a smaller number of unfavourable replies. Against
      expectations, adverse ideas were recorded in the group of subjects training for
      nursing. Employees of the law court and prosecution used most frequently adverse
      expressions and made the smallest number of statements expressing the necessity
      of assistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269528
TI  - [The solitary kidney in patients after nephrectomy in Wilm's tumor].
AB  - A single kidney in patients with agenesis or after nephrectomy is regarded as a
      risk factor. Primarily, the role of glomerular hyperfiltration and later possible
      glomerular sclerosis are emphasised. Complex treatment of Wilms tumour patients
      includes previous chemotherapy and radiotherapy. The aim of our study was to
      investigate late sequelae of this aggressive treatment on the morphology and
      function of a single kidney and to compare these results with a group of single
      kidney patients, where the diagnosis of Wilms tumour was excluded.

PMID- 8269529
TI  - [Surgical treatment of pectus excavatum and pectus carinatum].
AB  - The authors present their experience with surgery of deformities of the chest
      wall in childhood. In the course of 1986 to 1992 they operated 93 children with
      the diagnosis of pectus excavatum. This number comprised 66 boys and 27 girls.
      The mean age of the operated children was 10.5 years. During the same period 17
      patients (12 boys and 5 girls) were operated on account of pectus carinatum. The
      mean age of the latter group of patients was 13.5 years. 23% of the patients with
      a pectus excavatum had before operation mild scoliosis, two patients suffered
      from severe scoliosis. 76 patients after operation of pectus excavatum were
      followed up for more than one year after operation. In 44 patients the result was
      excellent (58%), in 31 patients the result was good. One patient developed a
      relapse. Fifteen patients after operation for pectus carinatum were followed up
      for more than one year. In 12 patients (80%) the result of the operation is
      excellent, in three patients (20%) the result is good. From the group as a whole
      seven patients had dehiscence of the wound after surgery, four patients developed
      a seroma in the surgical wound, three patients developed pneumothorax after
      operation and in one instance an abscess developed in the surgical wound. In the
      course of 1987 the authors changed the surgical technique in pectus excavatum
      from Jensen's to Holcomb jun. operation.

PMID- 8269530
TI  - [Metabolic study in a child with Leigh's syndrome and deficient activity in
      complex I of the respiratory chain].
AB  - Leigh's syndrome--subacute necrotizing encephalomyopathy--is a serious disease of
      child age manifested by severe psychomotor retardation, a varied neurological
      symptomatology, a typically symmetrical neuropathological affection of the
      central nervous system in the area of the basal ganglia and a metabolic disorder
      affecting the energy system of cells. The authors describe the clinical course of
      the disease and the results of metabolic and neuropathological investigations in
      an infant with Leigh's syndrome and severe lactate acidosis based on deficiency
      of complex I activity of the respiratory chain.

PMID- 8269531
TI  - [Hepatobiliary disorders in chronic nonspecific intestinal inflammation].
AB  - In 1977-1992 chronic inflammatory bowel disease was diagnosed in the
      gastroenterological department at the Clinic of Pediatrics in 31 children.
      Idiopathic proctocolitis was diagnosed in 16 children--mean age at the time of
      diagnosis was 13 years and 9 months. Fifteen children were treated for the
      diagnosis of Crohn's disease. Their mean age was 12 years and 9 months. During
      the investigation period all patients were examined regularly with special
      attention to hepatobiliary disease. Elevated aminotransferase values were
      observed in four children, three of these children have had permanent elevation
      of aminotransferase. Percutaneous liver biopsy revealed chronic persistent or
      active hepatitis. The authors investigated the course of the liver disease in
      relation to GIT disease. In the discussion they analyze the incidence,
      etiopathogenesis and type of liver lesions in inflammatory bowel disease with
      regard to the case-histories of their three patients.

PMID- 8269532
TI  - [Development and interrelations between certain respiratory and biochemical
      parameters in normal neonates].
AB  - The authors investigated the development and interrelations of respiratory and
      biochemical parameters of normal neonates during the adaptation period from 15
      minutes to the 7th day after delivery. They found that the correlations of oxygen
      consumption, carbon dioxide output, respiratory volume and minute ventilation are
      positive and independent on the time of assessment. These respiration parameters
      are independent on the glucose, lactate and pyruvate levels, on the respiratory
      quotient and pH and pCO2. The authors characterize the similarity of the trend of
      individual parameters and the variability of normal values.

PMID- 8269533
TI  - [Essential fatty acids in neonates at risk and in the mother's milk].
AB  - The participation of essential fatty acids and their derivatives in the blood
      (serum) of physiological healthy neonates (physiological pregnancy, physiological
      delivery) is compared with the spectrum of essential fatty acids of risk newborns
      (prematurity, prematurity with the tocolytic therapy and hypotrophic newborns).
      In the following part the presence and participation of essential fatty acids in
      the human maternal milk were measured. The milk of healthy mothers, of mothers
      with preterm delivery (37 week of gestation), of diabetic mothers were mutually
      compared and finally the values of mentioned essential fatty acids in formula
      Feminar and in the milk from the bank were established. As a consequence of our
      observations, they point out the absence or serious deficit of some essential
      fatty acids in certain groups of risk newborns as well as in the milk of diabetic
      mothers, of mothers with preterm delivery and in Feminar and Milk-bank. The
      presented facts--after their opinion--could be well judged as a rational basis
      for adequate nutritional therapy in risk newborns.

PMID- 8269534
TI  - [Alpha 1-antitrypsin deficiency--a hereditary storage disease of the hepatic
      endoplasmic reticulum].

PMID- 8269535
TI  - [Pulmonary hemorrhage in a neonate].
AB  - The authors describe a case of pulmonary haemorrhage in a neonate associated with
      adnatal pneumonia and infection with Staphylococcus epidermidis. The authors
      discuss the problem of this serious complication of the neonatal period as well
      as the limited diagnostic and therapeutic possibilities.

PMID- 8269536
TI  - [Incidence of celiac disease in northern Moravia 1965-1989].

PMID- 8269537
TI  - [Liquid ventilation--1].
AB  - The authors investigated in detail the sorption and desorption of oxygen and
      carbon dioxide in a solution of perfluorocarbons (solution RM 101, Miteni,
      Italy). From the results of the investigation ensues that maximal oxygen
      saturation of 77.3 vol.% can be achieved at 8 degrees C. With rising temperature
      the oxygen concentration in the solution declines (67.6 vol.% at 37 degrees). The
      saturation of the RM 101 solution corresponds to a linear equation of seventh
      order (fig. 2). Desorption of the RM 101 solution fully saturated with carbon
      dioxide, is on the other hand, most rapid at 37 degrees C (after the 13th minute
      the RM 101 solution contains less than 2% carbon dioxide as compared with 25
      vol.% at 8 degrees C during the same period. In general the kinetics of
      desorption of carbon dioxide in solution correspond to a linear equation of fifth
      order (fig. 4). From the practical aspect it is not expedient to saturate the RM
      101 solution with oxygen longer than 15-20 minutes. The mentioned kinetic
      parameters are important for the construction of a special liquid membrane or
      bubble oxygenator. In particular the latter is useful as with its use the authors
      achieved a 1.9 x higher oxygen concentration in the RM 101 solution than declared
      by the manufacturer.

PMID- 8269538
TI  - [The 5th nation-wide anthropological study of children and adolescents held in
      1991 (Czech Republic)--selected anthropometric characteristics].
AB  - The Vth nation-wide survey of children and adolescents which was conducted in
      autumn 1991 under new conditions comprised again, similarly as the four previous
      ones, a representative sample selected by random sampling. As compared with the
      1981 survey, the anthropometric parameters were extended by the circumference of
      the relaxed left arm and the hip circumference. A questionnaire for parents was
      elaborated where by a quite new approach was used. The still positive action of
      the secular trend of increasing height was confirmed. The action of the trend
      shifts to younger age groups, as compared with former surveys. The present survey
      confirmed also a tendency towards slimness in both sexes, however, in particular
      in girls a shift of this tendency to younger age groups was apparent. It will be
      certainly necessary to evaluate in future whether this trend reflects also a more
      favourable ratio of body composition. With regard to these changes the authors
      submit new percentile charts for evaluation of height, proportionality, and for
      children under three years, also head circumference.

PMID- 8269539
TI  - [Report on traffic casualties and their sequelae in the city and district of
      Uherske Hradiste].

PMID- 8269540
TI  - Expression of disodium cromoglygate 'protective' effects observed during V79 cell
      proliferation.
AB  - Disodium cromoglycate (DSCG) in equimolar concentration of 0.56 mumol/l
      preincubated with an asynchronous cell population decreases the inhibition of
      proliferation and results in a 100% elimination of inhibition of colony formation
      induced by benfluron (BF). DSCG protects the cells from unbalanced growth and
      unbalanced metabolism (e.g., prevention of increase or decrease in protein cell
      content, glycolytic activity and in amino acid metabolism) which are both the
      integrating parts of BF cytotoxic reaction. The protective effect of DSCG is
      manifested also on synchronous cell populations, particularly in G2 phase (26%).
      DSCG also stabilizes cell membrane by preventing the alterations of its
      permeability caused by the cytolytic concentrations of benfluron (at a
      concentration of 1.05 mumol/l and more).

PMID- 8269541
TI  - Tissue-type plasminogen activator induces alterations in structure and
      conformation of membrane proteins upon its interaction with human platelets.
AB  - In our very recent ESR study we reported that upon rt-PA binding to platelets the
      H+1/h0 ratios of 16-doxylstearate and 5-doxylstearate spin labels incorporated
      into the lipid bilayer of platelet membranes were significantly decreased. It
      corresponded to the increased rigidity of platelet lipid bilayer. In order to
      further explore this phenomenon we employed a fluorescence-quenching technique
      which enabled us to estimate the energy transfer efficiency and the apparent
      interchromophore distance between membrane protein tryptophan and 1-anilino-8
      naphthalenesulphonate (ANS) molecules embedded in the membrane lipid bilayer. As
      t-PA interacts with the platelet membrane this distance decreases, resulting in
      the relevant increase of energy transfer efficiency. Thus, the data indicate that
      upon t-PA binding the membrane tryptophan residues are more exposed to the
      external environment and the quenchable fraction of membrane tryptophan becomes
      greater. Furthermore, the spectrum of ANS is slightly shifted towards longer
      wavelengths, which can be accounted for by an increase in the polarity of the
      environment. It suggests a diminished contact of membrane tryptophan with
      phospholipid fatty acids. Based on these observations we concluded that the
      interaction of rt-PA with platelet membranes might induce conformational changes
      in the membrane proteins, and consequently result in rearrangements of lipid
      matrix and the alterations in lipid-protein interactions in platelet membranes.

PMID- 8269542
TI  - Evaluation of the tumor-initiating activity of 4-, 5-, 6-, and 7
      fluorobenzo[b]fluoranthene in mouse skin.
AB  - Benzo[b]fluoranthene and 4-, 5-, 6-, and 7-fluorobenzo[b]fluoranthene were
      evaluated for tumor-initiating activity in mouse skin. These fluorinated
      benzo[b]fluoranthene derivatives were assayed at doses of 400, 120, 40, and 10
      nmol per mouse. Similar tumorigenic activity was observed for
      benzo[b]fluoranthene and 5-fluorobenzo[b]fluoranthene. While 4
      fluorobenzo[b]fluoranthene did produce a significant tumorigenic response at each
      dose assayed, substantially fewer tumors per mouse were observed compared to
      benzo[b]fluoranthene at initiator doses at or above 120 nmol. Only moderate
      tumorigenic activity was observed for 6- and 7-fluorobenzo[b]fluoranthene. Both
      of these fluorinated derivatives were significantly less tumorigenic (P < 0.05)
      than 4-fluorobenzo[b]fluoranthene when administered at initiator doses at or
      below 120 nmol. These results were unanticipated in view of data which indicate
      that metabolism of trans-9,10-dihydro-9,10-dihydroxybenzo[b]-fluoranthene to
      trans-9,10-dihydro-5,9,10-trihydroxybenzo[b]fluoranthene represents a principal
      activation mechanism of benzo[b]fluoranthene in mouse skin. The potential of
      fluorine substitution not only to inhibit metabolism, but also to alter the
      genotoxic activity of those metabolites which do form could explain the
      tumorigenic activity observed with these fluorinated derivatives of
      benzo[b]fluoranthene. These data suggest caution in the interpretation of results
      based exclusively upon the assumption that the only influence of fluorine
      substitution is inhibition of the formation of specific metabolites.

PMID- 8269543
TI  - Synergistic activity of polynuclear aromatic hydrocarbon mixtures as aryl
      hydrocarbon (Ah) receptor agonists.
AB  - The relative potencies of benzo[a]pyrene and a complex mixture of polynuclear
      aromatic hydrocarbons (PAHs) produced as by-products of manufactured gas plant
      (MGP) residues as inducers of hepatic microsomal ethoxyresorufin O-deethylase
      (EROD) activity were determined in the B6C3F1 mouse. The ED50 values for the
      induction response were 78 and 65 mg/kg for benzo[a]pyrene and the MGP-PAH
      mixture, respectively. Analysis of the MGP-PAH mixture indicated that
      benzo[a]pyrene and other compounds containing four or more rings and which are
      known to induce EROD activity were only present as trace components of this
      mixture. A comparison of the EROD induction potencies of benzo[a]pyrene and the
      MGP-PAH mixture showed that the mixture was approximately 706 times more potent
      than expected based on its benzo[a]pyrene content (0.17%). This induced P-450
      activity could significantly increase the metabolism of the carcinogenic PAHs and
      thereby modulate the overall carcinogenicity of the mixture. The apparent
      synergistic activity of the MGP-PAH mixture was further investigated by comparing
      the activities of this mixture and benzo[a]pyrene for several other aryl
      hydrocarbon (Ah) receptor-mediated responses including (i) induction of hepatic
      CYP1A1 mRNA levels, (ii) transformation of the rat cytosolic Ah receptor to a
      complex which binds to a dioxin responsive element, (iii) induction of EROD
      activity and (iv) antiestrogenicity in MCF-7 human breast cancer cells, and (v)
      inhibition of the splenic plaque-forming cell (PFC) response to both T cell
      dependent and independent antigens in B6C3F1 mice. For the EROD and CYP1A1 mRNA
      induction and cytosolic transformation activities and immunosuppressive effects,
      the MGP-PAH mixture was approximately 100-900 times more potent as an Ah receptor
      agonist than expected based on its benzo[a]pyrene content. The synergistic
      activity was lower (19-fold) for the antiestrogenic response in MCF-7 cells. The
      reason for the synergistic effects of the MGP-PAH mixture were not due to
      contamination of the mixture by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related
      compounds and the results suggest that the enhanced potency of the mixture is due
      to unknown interactions between the individual PAHs present in the mixture.

PMID- 8269544
TI  - Sites of inhibition of mitochondrial electron transport by cadmium.
AB  - Cadmium is an extremely toxic environmental contaminant having a long half-life
      in humans. The greatest accumulation occurs in the liver and kidneys. Since
      mitochondria are the most sensitive targets, the effect of cadmium on the oxygen
      consumption and on the redox state of electron carriers of rat liver mitochondria
      has been evaluated. Cadmium markedly inhibits uncoupler-stimulated oxidation on
      various NADH-linked substrates as well as that of succinate. Experiments on
      specific segments of the respiratory chain showed that cadmium does not inhibit
      electron flow through cytochrome oxidase, whereas the inhibition of duroquinol
      oxidation clearly demonstrates an impairment of electron flow through site 2, the
      ubiquinone-b-cytochrome c1 complex. On the basis of the ability of N,N,N',N'
      tetramethyl-p-phenylendiamine and 2,6-dichlorophenolinindophenol bypasses to
      relieve the cadmium inhibition of succinate oxidation and on the spectroscopic
      behaviour of the cytochrome b, the inhibition was found to take place before
      cytochrome b and, more precisely, between ubisemiquinone and cytochrome bT.
      Furthermore, the finding that cadmium induces a more oxidized state of cytochrome
      b in state 1 demonstrates the existence of a second point in which it inhibits
      electron transfer. Spectroscopic evidence demonstrates that cadmium induces an
      oxidation of NAD(P)H in mitochondria in states 1 and 4 and prevents the reduction
      of mitochondrial NAD(P)+ by substrates, thus indicating that the site must be
      localized between NAD-linked substrates and respiratory chain.

PMID- 8269545
TI  - The relationship between the effect of biphenylcarboxylic acid analogs on
      glyceride synthesis and conformation.
AB  - The inhibition of biphenylcarboxylic acid analogs on glyceride synthesis was
      studied in association with conformation of the chemicals. Chemicals used were
      benzoic acid substituted with phenyl, benzoyl and phenoxy groups,
      phenylphenyloxyacetic acid and p-phenylacetic acid. Twist angles were calculated
      by a molecular orbital method. Following oral administration of p-phenylbenzoic
      acid to the rats for 7 days, the decrease of the triglyceride synthesized from
      [14C]oleic acid was observed in the adipose tissue. The in vitro inhibitions on
      the formation of fatty acyl-CoA thioester were examined from the influence on the
      hippuric acid formation from [14C]benzoic acid using the rat liver slices. In the
      homologous series, high inhibition was observed in para and meta substituents.
      None, or low inhibitions of ortho-substituted chemicals were related to the
      steric hindrance of the phenyl ring against carboxyl groups. This hinderance was
      associated with conformation and with the geometrical relationship between
      substituted phenyl rings and carbon atoms of carboxylic acid. In the in vitro
      inhibition on overall formation of diglyceride and triglyceride from
      [14C]glycerol, o-phenylbenzoic acid showing no inhibition on hippuric acid
      formation did not show inhibition. However, other ortho-substituted chemicals
      showed higher inhibition in comparison with the inhibition on hippuric acid
      formation. The inhibition of para- and meta-substituted chemicals were higher
      than the corresponding values of ortho substituted compounds.

PMID- 8269546
TI  - Reactive intermediates in the oxidation of hydralazine by HOCl: the major oxidant
      generated by neutrophils.
AB  - The use of the antihypertensive hydralazine is associated with an autoimmune
      syndrome resembling systemic lupus erythematosus. Adverse drug reactions, such as
      drug-induced lupus, often involve reactive intermediates. Oxidation of
      hydralazine by liver microsomes or activated leukocytes leads to reactive
      intermediates that covalently bind to protein and may be involved in hydralazine
      induced lupus. Oxidation of hydralazine to a reactive intermediate by cells
      involved in immune response, such as leukocytes, would be more likely to lead to
      an autoimmune reaction, such as drug-induced lupus, than would oxidation by cells
      in the liver. Leukocytes possess a defense system that generates HOCl in response
      to invading microorganisms. Hydralazine was oxidized to a reactive intermediate
      by HOCl generated by activated leukocytes. The reactive intermediate was trapped
      with N-acetylcysteine and the adduct was identified as 1-phthalazylmercapturic
      acid. The reactive intermediate is likely the diazonium salt of hydralazine. Two
      stable products were formed in the reaction, phthalazine and phthalazinone.
      Although phthalazine is oxidized to phthalazinone by HOCl, the rate of the
      reaction is much too slow to explain the rapid production of phthalazinone. It is
      more likely that most of the phthalazinone is formed by reaction of the putative
      diazonium salt with water. We propose that this reactive metabolite is
      responsible for hydralazine-induced lupus.

PMID- 8269547
TI  - A nitro radical anion formation from nifedipine: an electrochemical approach.
AB  - The cyclic voltammetric behaviour of nifedipine was studied. The addition of
      three aprotic solvents to nifedipine in an aqueous citrate buffer system was
      examined. Qualitatively they result in separation of the initial irreversible 4
      electron reduction into two stages, the NO2/RNO2.- and RNO2.-, 4H/RNHOH, H2O
      couples, respectively. Particular attention was directed to the 1-electron
      RNO2/RNO2.- couple as measured by the cyclic voltammetric mode in mixed media.
      Analysis of the cyclic voltammetric response as a function of scan rate and non
      aqueous solvent content yields information on the stability of the radical anion.
      The chemical forward reaction of the radical anion follows a second order
      kinetics with a stability constant of 1.1 x 10(-3) l mol-1 s-1 and a half-life
      time of 0.09 s for 1 mM of nifedipine in aqueous citrate buffer, pH 7.4/DMF;
      50:50.

PMID- 8269548
TI  - Liver accumulation of 2,3,7,8-tetrachloro-[3H]dibenzofuran in mice: modulation by
      treatments with polychlorinated biphenyls.
AB  - The distribution of 2,3,7,8-tetrachloro-[3H]dibenzofuran ([3H]TCDF; 40
      micrograms/kg) resembled that earlier reported for 2,3,7,8-tetrachlorodibenzo-p
      dioxin, with a strong accumulation in the liver and a selective uptake in the
      nasal olfactory mucosa of adult and fetal mice. Pretreatments with a series of
      selected congeners of polychlorinated biphenyls (PCBs), i.e.. I (IUPAC)-77, I
      105, I-118, I-126, I-153, I-156, I-169, and a commercial preparation, Aroclor
      1254 (25-100 mg/kg body wt. i.p.), were found to modulate the hepatic uptake of
      [3H]TCDF (24 h post-3H-injection). At a short pretreatment time (4 h), non-ortho
      chlorinated congeners decreased the uptake of [3H]TCDF equivalents in the liver
      (e.g., I-126 = 3,3',4,4',5-pentachlorobiphenyl: 34% of control), while several
      mono- and di-ortho PCB congeners and Aroclor 1254 increased the hepatic uptake of
      [3H]TCDF (e.g., I-156 = 2,3,3',4,4',5-hexachlorobiphenyl: 183% of control). At a
      longer pretreatment time (48 h), both a non-ortho (I-169 = 3,3',4,4',5,5'
      hexachlorobiphenyl) and mono-ortho PCB congener(s) (e.g. I-156) markedly
      increased the hepatic 3H-uptake (190%), a probable effect of an induction of
      hepatic binding sites for TCDF. Ethoxyresorufin-O-deethylase activities, regarded
      to mirror the metabolic activity of cytochrome P-450 IA1 (CYP IA1), were strongly
      and time-dependently induced after I-169, but not after I-156, pretreatment (25
      mg/kg). The initial liver concentrations of the two PCB congeners were similar
      and increased for I-169 but not for I-156 at later time points. In conclusion,
      the results show a selective uptake of [3H]TCDF in the mouse liver and nasal
      olfactory mucosa of both dam and fetus. The uptake of [3H]TCDF in the liver is
      influenced both by dose and pre-exposure with PCBs. The presence of a PCB
      sensitive, but CYP IA1-independent, hepatic binding site for TCDF is suggested.
      Consequently, pharmacokinetic interactions with PCBs complicate the toxicity
      assessment of TCDF in complex mixtures.

PMID- 8269549
TI  - Composition and toxicity of diethyl ether soluble lipids from Nocardia asteroides
      GUH-2 and Nocardia asteroides 10905.
AB  - Virulent Nocardia asteroides GUH-2 and avirulent N. asteroides 10905 contained
      8.2% and 10.6% of diethyl ether soluble lipids (DESL) per dry cell mass,
      respectively. Intraperitoneal (i.p.) inoculation of 250 micrograms of DESL from
      GUH-2 dissolved in mineral oil was toxic to mice, resulting in weight loss and
      death of 100% of the animals (20/20) within 20 days. In contrast, DESL from 10905
      had very little toxicity, and only one mouse (1/10) died within 30 days. Three
      fractions resulted from DESL by silicic acid column chromatography: (1) neutral
      lipids and fatty acids (NFA); (2) glycolipids (GL); and (3) phospholipids (PL).
      Each fraction dissolved in mineral oil was inoculated into mice as described
      above. The NFA and PL were not toxic. GL from 10905 had low toxicity (30% of the
      animals died, 3/10) whereas GL from GUH-2 expressed high toxicity (100% of the
      animals became cachetic and died, 10/10). GL from 10905 represented a minor
      component (0.6% of dry cell weight) whereas GL from GUH-2 was more prominent
      (1.5% of dry cell wt.). Approximately 95% of GL from GUH-2 had properties of an
      authentic trehalose-6,6'-dimycolate standard. Infrared spectrum of the major
      glycolipid (GUH-2 GL) had characteristic absorptions in the fingerprint region
      between 800 cm-1 and 1500 cm-1. Upon alkaline hydrolysis GUH-2 GL released 76%
      mycolic acids in the C50 size range plus 24% trehalose.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8269550
TI  - Ion-induced fusion of phosphatidic acid vesicles and correlation between surface
      hydrophobicity and membrane fusion.
AB  - Divalent cation (Ca2+ and Mg2+) and hydrogen ion-induced fusions of small
      unilamellar phosphatidic acid vesicles were studied by the use of fluorescence
      fusion assay. These fusogenic ions also increased interfacial tension and reduced
      the surface dielectric constant of phosphatidic acid membranes as the ion
      concentration increased. A good correlation was found between the threshold of
      vesicle fusion and the degree of changes in such membrane properties induced by
      these fusogenic ions. At the fusion threshold point, the increase in interfacial
      tension and the decreased surface dielectric constant of the membrane were
      approximately 6 and 14 dyn/cm, respectively, regardless of Ca2+, Mg2+ or H+. Such
      changes correspond to the increases in surface hydrophobicity of the membrane. As
      these fusogenic ionic concentrations increased, the electrophoretic mobility of
      the phosphatidic acid vesicle decreased, because of the binding of ions to
      negatively charged sites of the membranes. However, the quantities of the reduced
      negative surface charges were not necessarily in good correlation with the
      threshold of vesicle fusion. It is suggested that the complexes of the phosphate
      group with these fusogenic ions are responsible for increases in the surface
      hydrophobicity of the membrane, which is an important factor for membrane fusion.

PMID- 8269551
TI  - The effect of anaesthetics on the dynamic heterogeneity of lipid membranes.
AB  - The influence of membrane-perturbing drugs such as anaesthetics on the lipid
      membrane properties is analyzed theoretically on the basis of a general
      microscopic interaction model of the gel-to-fluid chain melting transition of one
      component phospholipid membranes and phospholipid membranes with a low content of
      cholesterol. Monte Carlo computer simulation of the model shows that the gel-to
      fluid transition of the lipid membrane, manifested in the formation of
      dynamically coexisting domains of gel and fluid lipids, is strongly influenced by
      the presence of anaesthetics. Macroscopically the effect of anaesthetics on the
      membrane properties is seen in a depression of the transition temperature and a
      smearing of thermodynamic response functions like the specific heat.
      Microscopically the calculations reveal that anaesthetics have a high affinity to
      the fluctuating domain interfaces that are dominated by kink-like lipid-chain
      conformations. This leads to formation of more interfaces and to a locally high
      concentration of anaesthetics in the interfacial regions, which is much larger
      than the global concentration in the membrane. Important membrane components like
      cholesterol, which also has been shown to be interfacially active, are found to
      decrease the absorption of anaesthetics and to squeeze out anaesthetics from the
      interfaces. The results of the general model study of anaesthetics-membrane
      interactions are discussed in relation to both general anaesthetics, like
      halothane, and local anaesthetics like cocaine-derivatives.

PMID- 8269552
TI  - Molecular parameters of semisynthetic derivatives of gangliosides and sphingosine
      in monolayers at the air-water interface.
AB  - The molecular parameters (molecular area, surface potential, collapse pressure,
      dipole moment contributions) of semisynthetic derivatives of ganglioside GM1 and
      of sphingosine were studied in lipid monolayers at the air-NaCl (145 mM, pH 5.6)
      interface at 22 +/- 0.3 degrees C. The chemical modifications included
      alterations of the fatty acyl chain moiety linked to the 2-amino position of the
      sphingosine (Sph) base. The compounds studied were PKS-1 (N-acetyl Sph), PKS-2 (N
      chloroacetyl Sph), PKS-3 (N-dichloroacetyl Sph), PKS-4 (N-trichloroacetyl Sph),
      Lyso-GM1 (ganglioside GM1 lacking the N-linked fatty acyl chain and the N-acetyl
      group on the sialic acid), Liga-4 (N-acetyl, lyso[NeuAc]GM1) and Liga-20 (N
      dichloroacetyl, lyso[NeuAc]GM1). Relatively small modifications of the chemical
      structure of sphingolipids introduce dramatic consequences on their surface
      molecular properties. The absence of the long chain fatty acyl moiety and of the
      N-acetyl group on the neuraminic acid in Lyso-GM1 leads to a more condensed
      behavior and to an increase of the collapse pressure compared with GM1. The
      acetylation or chloroacetylation at the 2-amino position in Liga-4 and Liga-20
      induce an expansion of the surface pressure-area isotherm and a decrease of the
      collapse pressure. The limiting molecular areas of GM1 derivatives, taken at the
      collapse pressure point, are consistent with the oligosaccharide chain being
      oriented approximately perpendicularly to the interface. Sphingosine shows a
      liquid expanded isotherm. The acetylation and successive chlorination of the
      acetyl residue at the 2-amino position of Sph cause a progressive increase in the
      limiting molecular area. The variation of the resultant dipole moment under
      compression, calculated from the surface potential values, suggests the
      reorientation of selective groups within these molecules that depend on the
      degree of intermolecular packing. Thermodynamic-geometric correlations on the
      basis of the molecular parameters of these derivatives suggest that small
      alterations of the substituent group at the 2-amino position of Sph could have
      large and amplified consequences on the type, curvature and stability of the
      possible self-aggregated structure that these lipids may form in aqueous medium.

PMID- 8269553
TI  - A comparison of daily fluoride intakes from food samples in Japan and Brazil.
AB  - The purpose of this study was to analyse the fluoride content of Japanese infant
      foods and foods in Brazil and to estimate daily fluoride intake calculated for a
      6-month-old infant which reflects supplemental fluoride increased from infant
      foods and decreasing breast-feeding and commercial milk-feeding. Fluoride
      concentrations of 26 samples were assessed by a modified microdiffusion method
      and fluoride ion selective electrode. The fluoride content varied from 0.53 to
      1.33 microgram/g for milk-base formulas, from 0.46 to 2.94 micrograms/g for
      infant foods in Japan, and from 0.06 to 0.25 microgram/g for foods in Brazil. The
      daily fluoride intake was calculated according to feeding pattern. The minimum
      and maximum fluoride values were 0.080 mg/day and 0.248 mg/day, respectively.
      These fluoride intakes, expressed in milligrams per kg of fluoride intake, ranged
      from 0.010 to 0.033 mg F/kg body weight. No significant differences in fluoride
      intake values were found between Japanese infant foods and foods in Brazil. The
      results of this study indicate that daily fluoride intakes of Japanese infant
      foods and foods in Brazil could be considered within the optimal recommended
      level.

PMID- 8269554
TI  - Morphometric analysis of image distortion with rotational panoramic radiography.
AB  - We studied the image distortion of spherical objects that occurred during
      rotational panoramic radiography. We measured the magnification of height, width,
      perimeter and area, and calculated the circularity index to quantify the
      distortion. Spherical objects of different diameters were projected on the film.
      A complex relationship was found between the position and the horizontal
      magnification for each anatomical region. The object's size influenced the
      horizontal magnification to a considerable extent. The greatest changes in
      circularity occurred at the midline. This morphological distortion was caused by
      non-symmetrical projection during the scanning of these spherical objects, which
      resulted from the continuous changes in the scanning velocity and the position of
      the x-ray beam. This result suggests a complex distortion of the inner structures
      of macroscopic objects.

PMID- 8269555
TI  - Cytoskeletal organization in fibroblasts of rat calvaria periosteum:
      microfilaments demonstrated by detergent perfusion.
AB  - The authors examined the microfilament of fibroblasts in rat calvarial periosteum
      by transmission electron microscopy after perfusing rats with a mixed solution of
      Triton X-100 and a low concentration of glutaraldehyde. Fibroblasts in the
      periosteum were fusiform and had elongated oval nuclei. Microfilaments with
      diameters of 5-6 nm were noted within the cytoplasm. Although these
      microfilaments were parallel to the long axis of the cell, stress fibers, which
      are thick bundles of microfilaments present in cultured fibroblasts, were not
      observed in these fibroblasts.

PMID- 8269556
TI  - Scanning electron microscopic observation on the dentin surface of rat enamel
      free areas.
AB  - Formation of the enamel covering on the dentin of the tooth crown is thought to
      depend upon the dentin surface structure during the early stages of enamel
      development. For this reason, observations were made of the dentin surfaces of
      both the enamel-free area (EFA) and the region beneath the enamel area. After
      treatment with sodium hypochlorite and formic acid, scanning electron microscope
      observations were made of the EFA surface and the exposed dentin surface beneath
      the enamel of unerupted rat mandibular first molars. Cone-like projections
      consisting of matrix fibers were observed on the dentin surface covered with the
      enamel. These cone-like projections formed continuous ridges that connected with
      the network structure. At the concavities of these network structures these
      projections were distributed sparsely. Instead of the cone-like projections, the
      matrix fibers formed a coarse network structure along the surface at the EFA.

PMID- 8269557
TI  - A study of the influence of arrangement of upper posterior artificial teeth on
      pronunciation: Japanese sounds articulated on the posterior palate.
AB  - To clarify the standard of bucco-lingual tooth arrangement in complete denture
      construction, the influence of the bucco-lingual position of upper posterior
      artificial teeth on pronunciation was investigated. Wearing 7 kinds of
      experimental artificial teeth with the upper posterior ones arranged in 7
      different positions, patients pronounced 5 test sounds: "ka", "ki", "kw", "ke"
      and "ko". Resultant sounds were evaluated in terms of how the bucco-lingual
      position of posterior artificial teeth influenced pronunciation as determined
      with by aural pronunciation judgment test and frequency analysis using a 1/3
      octave-band real-time analyzer. Pronunciation disorders caused by the arrangement
      of the upper posterior artificial teeth in complete dentures occur when the
      lingual surfaces of the upper molars is located more than 1/4 inward of the
      distance between the right and left denture border from the buccal denture border
      or less than 1/10 of that distance outward from the buccal denture border.
      Results of the aural pronunciation judgment test indicated that the influence of
      the arrangement of the upper posterior artificial teeth on pronunciation depends
      on the vowel following the consonant of the sound. When the vowel following the
      consonant is a back vowel, as in "ka", "kw" and "ko" the sound was barely
      influenced, but when the vowel is a front vowel. as in "ke" and "ki", the sound
      was markedly influenced. We established the frequency spectrum of the consonant
      of the normally pronounced 5 test sounds as the standard frequency spectral range
      and compared distorted and misheard sounds with it.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8269558
TI  - A study of the judging the anteroposterior mandibular position by gripping the
      temporal muscle region.
AB  - Greene proposed a method for judging the suitability of the mandibular position
      from the bulging of the temporal muscle. Using his method, we studied the effect
      of anteroposterior alteration of mandibular position on the building of this
      muscle. In the temporal muscle, the area suitable for gripping to check
      mandibular position was, anteroposteriorly, the point 3/5 of the length between
      the upper margin of the external auditory meatus and the point of intersection of
      the Frankfort plane and the line perpendicular to it which was drawn from the
      outer canthus. Vertically, it was approximately at the point 3/5 of the distance
      from the bottom of the line from the Frankfort plane to the upper edge of the
      temporal muscle. In patients whose anteroposterior changes in the tapping point
      were small, anteroposterior changes of 0.2 mm in mandibular position could be
      detected. However, in patients who had large anteroposterior changes in the
      tapping point, anteroposterior changes of 0.5 mm in mandibular position could not
      be verified.

PMID- 8269559
TI  - Inflammation and cardiopulmonary bypass.

PMID- 8269560
TI  - Elevation of cytokines during open heart surgery with cardiopulmonary bypass:
      participation of interleukin 8 and 6 in reperfusion injury.
AB  - Myocardial ischaemia is one of the major causes of low output syndrome during
      open heart surgery. Injury associated with ischaemia and reperfusion has been
      considered to result, in part, from the action of neutrophils, the interaction of
      neutrophils with vascular endothelial cells, and the effects of cytokines which
      are mediators that induce and modify reactions between these substances. We
      investigated cell injury in relation to the concentrations of interleukins 6 and
      8 (IL-6 and IL-8), which have recently received attention as neutrophil
      activators. Neutrophil counts, granulocyte elastase (GEL), IL-6, IL-8, tumour
      necrosis factor-alpha (TNF-alpha), CK, and CK-MB concentrations were determined
      serially in 11 patients undergoing open heart surgery with cardiopulmonary bypass
      (CPB). Neutrophil counts (mean +/- SD 2717 +/- 2421 microliters-1 preoperatively)
      peaked 60 min after declamping the aorta at 7432 +/- 4357 microliters-1 (P <
      0.01) and remained elevated 7136 +/- 5194 microliters-1 at 180 min (P < 0.01).
      Plasma GEL level (168 +/- 71 micrograms.L-1 preoperatively) peaked at 1134 +/-
      453 micrograms.L-1 120 min after declamping of the aorta (P < 0.01) and remained
      elevated, 1062 +/- 467 micrograms.L-1, after 180 min (P < 0.01). Serum IL-6 level
      (118 +/- 59 pg.ml-1 preoperatively) peaked at 436 +/- 143 pg.ml-1 60 min after
      declamping of the aorta (P < 0.01) and remained elevated, 332 +/- 109 pg.ml-1,
      after 180 min. Serum IL-8 level (37 +/- 44 pg.ml-1 preoperatively) peaked at 169
      +/- 86 pg.ml-1 at 60 min after declamping of the aorta (P < 0.001) and remained
      elevated at 113 +/- 78 pg.ml-1 180 min after declamping of the aorta.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269561
TI  - Value of routine preoperative chest x-rays: a meta-analysis.
AB  - The purpose of this study was to estimate the frequency with which routine
      postoperative chest x-rays lead to clinically relevant new information. All
      articles in English, French and Spanish relating to routine chest radiography in
      North American or European populations were reviewed, using the Medline database
      and references listed in reviews and periodicals published from 1966 to 1992,
      inclusive. Twenty-one reports which supplied sufficient information were included
      for meta-analysis. On average, abnormalities were found in 10% of routine
      preoperative chest films. In only 1.3% of films were the abnormalities
      unexpected, i.e., were not already known or would not otherwise have been
      detected (95% CI: 0 to 2.8%). These findings were of sufficient importance to
      cause modification of management in only 0.1% (95% CI: 0 to 0.6%). The frequency
      with which the new information influenced health could not be estimated. Assuming
      only the direct cost to the health care system of each radiograph ($23), each
      finding which influenced management in any way would cost $23,000. It is
      concluded that in North American or European populations when a reliable history
      and a clinical examination are carried out, the cost of this test is so high
      relation to the clinical information provided that it is no longer justifiable.

PMID- 8269562
TI  - Orbicular muscle akinesia in regional ophthalmic anaesthesia with pH-adjusted
      bupivacaine: effects of hyaluronidase and epinephrine.
AB  - The success rate and duration of lid akinesia after adding hyaluronidase and/or
      epinephrine to pH-adjusted bupivacaine was examined in a double-blind fashion in
      patients undergoing cataract surgery under local anaesthesia. A two-injection
      site technique was used. For globe akinesia all patients (n = 120) received an
      inferolateral intraconal injection (3 ml) of pH-adjusted bupivacaine 0.75% and
      hyaluronidase. Lid akinesia was obtained with a medial extraconal injection (3.5
      ml) of alkalinized bupivacaine with or without an adjunct. The patients were
      randomized to four groups as follows: a medial injection of plain bupivacaine (n
      = 31), with added hyaluronidase (n = 30), with added epinephrine (n = 29) or with
      both epinephrine and hyaluronidase (n = 30). The final solutions had a pH of 6.7.
      Lid akinesia was supplemented with periosteal injections if needed. The degree of
      akinesia from clinical assessment was graded from 0-2 and also measured with
      electromyography at ten minute intervals for 30 min after surgery, and three
      hours after the block. The least satisfactory result (P < 0.01) and shortest
      duration of the lid block (P < 0.05) was obtained with plain pH-adjusted
      bupivacaine. No differences in the success rate or duration of the block among
      the other groups were seen. The duration of the block was longer in the
      epinephrine groups than in the two other groups (P < 0.01) and longer in the
      epinephrine and hyaluronidase group than in the group receiving only
      hyaluronidase (P < 0.05). We conclude that the best initial results and longest
      duration of blocks were shown in the groups receiving epinephrine or epinephrine
      and hyaluronidase.

PMID- 8269563
TI  - Secondary hyperalgesia is not affected by wound infiltration with bupivacaine.
AB  - The purpose of this study was to determine the effects of wound infiltration with
      bupivacaine on incisional pain and the zone of secondary hyperalgesia. Twenty
      eight healthy parturients were studied in a double-blind randomized trial. At the
      time of Caesarean section one wound edge was infiltrated with saline 0.9% and the
      other with bupivacaine 0.25%. After 24 hr, visual analogue scores were obtained
      for incisional pain and the zone of secondary pain around the incision was
      measured. Patients served as their own controls. Visual analogue scores for the
      bupivacaine side of the wound were less than for the saline side (P < 0.05). The
      zone of secondary pain was similar overall for both sides of the wound. It is
      concluded that the bupivacaine-infiltrated side of the wound was less painful
      than the saline-injected side 24 hr postoperatively. The zone of pain measured
      around the wound edges was unaffected by bupivacaine or saline.

PMID- 8269564
TI  - Capnometry and the paediatric laryngeal mask airway.
AB  - The laryngeal mask airway (LMA), an alternative to tracheal intubation in certain
      situations, has gained popularity in recent years. Initially designed for use in
      adults it has now become available in suitable sizes for paediatric anaesthesia.
      The objectives of this study were to identify the preferred site of sampling the
      end-tidal carbon dioxide (PETCO2) with the LMA and to determine the accuracy of
      this recording when compared with arterial CO2 (PaCO2). We studied 30 healthy
      children, age one to five years and weighing between 10 and 25 kg undergoing
      minor surgery requiring mask anaesthesia. In each case, after induction of
      anaesthesia, the LMA was inserted under direct vision to eliminate the
      possibility of epiglottic airway obstruction. The fresh gas flow was provided by
      a Jackson Rees modification of an Ayre's T-piece and was determined according to
      the following formula: 3 x (1000 + (100 x body weight)) LPM. Blood pressure, ECG,
      O2 saturation, temperature and end-tidal gas concentrations were recorded. The
      measures of peak PETCO2 were taken at pre-determined distances from the elbow
      connector down the LMA shaft. During the sampling sequence an arterial blood
      sample was taken for gas analysis. The PaCO2 was 63.5 +/- 9.3 mmHg (mean +/- SD).
      At any given sampling site, mean PETCO2 values were less than PaCO2 (P < 0.05).
      However, in eight patients PETCO2 values measured at the distal site were higher
      than the PaCO2 (negative P(a-ET)CO2 gradients).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269565
TI  - Time course in thoracic epidural pressure measurement.
AB  - The purpose of this study was to measure thoracic epidural pressure at the time
      of insertion of an epidural needle. The pressure was measured using a closed
      pressure measurement system after insertion of a Tuohy needle at the T7-8
      intervertebral level. This system is unique because it has a pressure transducer
      equipped with a device which regulates flow through the transducer and prevents
      the heparinized saline in the system from being evacuated into the epidural space
      due to sudden pressure change. As reported previously, high negative epidural
      pressures, up to -60 mmHg, were observed at the moment of epidural puncture.
      However, the pressure became positive in about 30 sec in 12 of the 13 patients,
      and stabilized at +3.7 +/- 3.2 mmHg (mean +/- SD) within 90 sec. Similar results
      were observed when the procedure was repeated within a few minutes to the same
      patients. This suggests that negative epidural pressures at the moment of
      epidural puncture are artifacts induced by tenting of the dural membrane.
      Subsequent adaptation of the surrounding tissue results in restoration of the
      normal positive epidural pressure.

PMID- 8269566
TI  - Tracheal tube leak test--is there inter-observer agreement?
AB  - Although the leak test is recommended as a method of assessing the appropriate
      size of uncuffed endotracheal tubes for use in children, the reproducibility of
      this test has not been validated. Patients from newborn to ten years of age
      requiring tracheal intubation for elective surgery were studied. The endotracheal
      tube size was calculated using the formula: (age + 16) divided by 4 for patients
      > or = two years of age and at the discretion of the attending anaesthetist for
      patients < two years of age. After the induction of anaesthesia and
      administration of a nondepolarizing muscle relaxant, the patient's trachea was
      intubated and mid-tracheal placement was confirmed. Two of the three staff
      anaesthetists participating in the study assessed the leak pressure
      consecutively. Each participant performed a single leak determination. The leak
      pressure was determined as follows: the patient was supine with the head in a
      neutral position, fresh gas flowed into the breathing circuit at 5 L.min-1, a
      stethoscope was placed on the skin over the larynx and the pressure relief valve
      was completely closed. Pressure slowly increased in the breathing circuit until
      an audible leak occurred around the tracheal tube. The inter-observer difference
      was calculated in 212 patients. The absolute value of the difference between that
      of two observers increased as the mean leak pressure increased. However, the
      variation between observers expressed as a percent of the absolute measurement
      remained constant. An average variance in measurement of 38% was found at both
      low and high leak pressures. In conclusion, we found considerable variation
      between two experienced observers in assessing leak pressures.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8269567
TI  - Cardiac electrophysiology and conduction pathway ablation.
AB  - Invasive cardiac electrophysiological (EP) testing and transcatheter ablation are
      new methods available for the diagnosis and treatment of complex dysrhythmias.
      The purpose of this review is to familiarize anaesthetists with these procedures.
      The information presented combines a literature review with the authors'
      experience. This article reviews normal cardiac conduction, tachycardia
      pathogenesis, principles of cardiac EP study and techniques of conduction pathway
      ablation. The anaesthetic considerations, including the choice of anaesthetic
      agent, monitoring problems, drug interactions, special methods of dysrhythmia
      termination in the EP lab, and complications specific to these procedures, are
      detailed. Balanced general anaesthesia or monitored anaesthesia care (MAC)
      sedation with benzodiazepines, propofol and narcotics are acceptable. Several
      conclusions can be drawn: transcatheter ablation is an effective treatment for
      many reentry tachycardias; anaesthetic assistance for this procedure will
      increasingly be needed; anaesthesia can easily be provided without influencing
      accurate EP testing; overdrive pacing is the method of choice for terminating
      tachydysrhythmias in the EP lab.

PMID- 8269568
TI  - Continuous regional anaesthesia in infants.
AB  - Physiological immaturity of the respiratory musculature and central respiratory
      control centres leads to an increased risk of apnoea and respiratory
      complications following general anaesthesia in neonates. Regional anaesthetic
      techniques may obviate the need for general anaesthesia and lessen the risks of
      perioperative morbidity. Although these techniques have been described in
      infants, previous reports have dealt with single-shot techniques for brief
      surgical procedures (< 60 min). Experience with prolonged operative cases using
      regional anaesthesia via indwelling catheters in infants is limited. We present
      our experience with four infants in whom either caudal epidural or spinal
      anaesthesia was administered via indwelling catheters for operative procedures
      that lasted 90 to 180 min. We believe this technique is an alternative to general
      anaesthesia in these patients.

PMID- 8269569
TI  - Catheter-induced pulmonary artery haemorrhage resulting from a pneumothorax.
AB  - We present a case of pulmonary artery perforation in a patient who developed a
      pneumothorax after cardiac surgery. In the process of inserting a chest tube the
      patient became tachypnoeic, and developed haemoptysis. The trachea was intubated,
      and right bronchial intubation was performed with persistent bleeding. The
      pulmonary artery catheter was gently withdrawn and the balloon inflated, with
      cessation of bleeding. The patient was taken to the operating room, a bronchial
      blocker was placed in the right lower lobe bronchi, and the pulmonary artery
      catheter was removed. The bronchial blocker was removed the following day with no
      bleeding. The aetiology of perforation was secondary to the pneumothorax, which
      caused a shift of the mediastinum to the right, elevated pulmonary artery
      pressures, and the distal migration of the catheter through the pulmonary artery.
      It is recommended that treatment include tracheal intubation, inflation of the
      pulmonary artery catheter balloon, and the placement of a right lower lobe
      bronchial blocker.

PMID- 8269570
TI  - Anaesthesia for thoracoscopic pulmonary lobectomy.
AB  - This report describes the anaesthetic management of a new surgical procedure-
      pulmonary lobectomy accomplished by minimal invasive surgery (MIS) techniques.
      Upper and middle pulmonary lobectomy were performed uneventfully during general
      anaesthesia in a 76-yr-old woman. No similar report has yet appeared in the
      literature. Important anaesthetic considerations include safety concerns, the
      need for differential lung ventilation, and the problems inherent in a lengthy
      operation. In the appropriate clinical setting, anaesthesia and surgery for major
      pulmonary resections accomplished by MIS techniques can be performed safely and
      effectively.

PMID- 8269571
TI  - Measurement of respiratory mechanics using the Puritan-Bennett 7200a ventilator.
AB  - This study was designed in order to validate the respiratory mechanical variables
      measured by the Puritan-Bennett 7200a ventilator equipped with the 30/40 module.
      Two ventilators were connected to a lung model and submitted to several breathing
      patterns by modifying the respiratory rate, the tidal volume, the inspiratory
      flow-rate and the model resistance. The inspiratory flow-rate (V), tidal volume
      (VT), peak inspiratory pressure (Pmax), plateau pressure (Pplat) and PEEP
      measured by the ventilators were compared with the same variables measured at the
      connection between the breathing circuit and the lung model. The compliance
      (C30/40) and the resistance (R30/40) calculated by the 30/40 module were compared
      with those calculated by using the variables measured by the reference equipment.
      Both ventilators made a constant underestimation of V by 2.8 and 3.7 L.min-1,
      respectively. The VT was measured with a mean error of less than 10 ml but did
      not reflect the preselected values in the presence of an intrinsic PEEP. The
      Pplat was overestimated by 7 and 10%, respectively. The same calibration error
      was observed with Pmax which was also affected by a pressure gradient due to the
      resistance of the breathing circuit. Even in the absence of intrinsic PEEP,
      C30/40 presented an error due to the combination of the measurement errors on VT,
      Pplat and PEEP. Finally, R30/40 presented a high percentage of error due to the
      combination of the measurement errors on V, Pmax, and Pplat, and to a sporadic
      aberrant selection of V. Due to these numerous sources of error, the two
      ventilators studied did not give reliable estimates of resistance and
      compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269572
TI  - Adrenocorticotrophic hormone, cortisol and catecholamine concentrations during
      insulin hypoglycaemia in dogs anaesthetized with thiopentone.
AB  - Glucose homeostasis is maintained by complex neuroendocrine control mechanisms.
      Increases in plasma concentrations of various glucose-raising hormones such as
      glucagon, catecholamines, adrenocorticotrophic hormone (ACTH), and cortisol are
      observed under certain conditions associated with stress (haemorrhage and
      hypoglycaemia). The purpose of this study was to determine the effect of
      thiopentone anaesthesia on the catecholamine, ACTH and cortisol response to
      insulin hypoglycaemia in dogs. Blood sugar (BS), plasma catecholamine, and ACTH,
      and serum cortisol concentrations were measured during the course of (1) an
      intravenous insulin test (ITT) and (2) an ACTH test in conscious and in
      anaesthetized fasted dogs. During the ITT, the anaesthetized dogs showed a
      moderate resistance, compared with conscious dogs, to the hypoglycaemic action
      induced by insulin (blood sugar concentration 30 min after insulin injection:
      2.91 +/- 0.25 vs 1.93 +/- 0.12 mM.L-1; P < 0.01). In addition, decreased
      epinephrine (220 +/- 27 vs 332 +/- 32 pg.ml-1), ACTH (65 +/- 6 vs 90 +/- 5 pg.ml
      1) and cortisol (4.48 +/- 0.3 vs 6.25 +/- 0.5 micrograms.ml-1) concentrations
      were detected 60 min after insulin injection (P < 0.01). The norepinephrine
      response to hypoglycaemia was not altered by anaesthesia (273 +/- 33 vs 325 +/-
      25 pg.ml-1). Anaesthetized dogs showed a decreased cortisol response to ACTH at
      45 min (5.68 +/- 0.54 vs 8.87 +/- 0.47 micrograms.ml-1) when compared with
      control dogs (P < 0.001). Haemodynamic variables during anaesthesia showed little
      changes (P < NS); while respiratory rate was altered (P < 0.01 between 60 and 105
      min).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269573
TI  - Invasive pressure monitoring of patients during magnetic resonance imaging.
AB  - The purpose of this paper is to describe a system for monitoring patients who
      require general anaesthesia, profound sedation or intensive care while undergoing
      high field (> or = 1.5 T) magnetic resonance (MR) imaging. Continuous evaluation
      of invasive and noninvasive pressures, inspired and end-tidal respiratory gas
      concentrations, body temperature, heart rate, ECG and pulse oximetry were
      measured successfully during the MR examination. Diagnostic quality MR images
      were acquired on all 15 monitored patients. The calculated signal-to-noise ratios
      were not different between the control and monitored patients. Commonly
      encountered technical problems and their solutions are described. This study
      demonstrates that invasive monitoring can be safely performed in critically ill
      patients who are undergoing high field MR examinations.

PMID- 8269574
TI  - Fresh gas flow and carbon dioxide rebreathing in a low pressure semi-open
      anaesthesia system.
AB  - We have constructed a simple system for field anaesthesia by using a Farman
      entrainer and a semi-open circuit to convert a draw-over apparatus to a
      continuous flow air/O2 system. Compressed O2 was the driving gas for the
      entrainer; fresh gas (FG) delivered to the semi-open circuit was a mixture of O2,
      entrained air and anaesthetic vapour. The purpose of this study was to examine FG
      flow rate and CO2 rebreathing during intermittent positive pressure ventilation
      (IPPV). A non-rebreathing inflation valve (Laerdal) placed at the end of the
      expiratory (efferent) limb of the circuit vented both expiratory gas and excess
      FG. Ambient air IPPV was applied through the Laerdal valve from a self-inflating
      bag or ventilator. Since this circuit is functionally similar to a T-piece, the
      gas from the efferent limb (340 ml, containing FG) entered the lungs first. If
      tidal volume was larger than 340 ml the balance was ambient air. Minute
      ventilation of the lungs with efferent limb gas was defined as Veff. Respiratory
      gas was sampled at the endotracheal tube and the CO2 tension was measured with a
      NIHON-KOHDEN CO2 analyzer. Thirty-seven adult patients having intra-abdominal or
      pelvic surgery under general tracheal anaesthesia were studied. Four FG flow
      rates (5.7, 8.0, 9.3, and 10.4 L.min-1), corresponding to driving gas pressures
      of 40, 60, 80, and 100 mmHg, were introduced in random order. Although inspired
      CO2 was detected at FG flow rates of 5.7-9.3 L.min-1, there were no differences
      in PETCO2 among the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269575
TI  - Canadian Anaesthetists' Society Gold Medal. Dr. Marcel Boulanger.

PMID- 8269576
TI  - Canadian Anaesthetists' Society Gold Medal. Dr. Douglas B. Craig.

PMID- 8269577
TI  - Canadian Anaesthetists' Society Gold Medal. Dr. Gordon R. Sellery.

PMID- 8269578
TI  - Similarity of drug labels predisposes to drug errors.

PMID- 8269579
TI  - Spinal subdural haematoma in a parturient after attempted epidural anaesthesia.

PMID- 8269580
TI  - Accidental total spinal.

PMID- 8269581
TI  - "If it squeaks, all is well".

PMID- 8269582
TI  - Statistical approaches to pharmacodynamic modeling: motivations, methods, and
      misperceptions.
AB  - We have attempted to outline the fundamental statistical aspects of
      pharmacodynamic modeling. Unexpected yet substantial variability in effect in a
      group of similarly treated patients is the key motivation for pharmacodynamic
      investigations. Pharmacokinetic and/or pharmacodynamic factors may influence this
      variability. Residual variability in effect that persists after accounting for
      drug exposure indicates that further statistical modeling with pharmacodynamic
      factors is warranted. Factors that significantly predict interpatient variability
      in effect may then be employed to individualize the drug dose. In this paper we
      have emphasized the need to understand the properties of the effect measure and
      explanatory variables in terms of scale, distribution, and statistical
      relationship. The assumptions that underlie many types of statistical models have
      been discussed. The role of residual analysis has been stressed as a useful
      method to verify assumptions. We have described transformations and alternative
      regression methods that are employed when these assumptions are found to be in
      violation. Sequential selection procedures for the construction of multivariate
      models have been presented. The importance of assessing model performance has
      been underscored, most notably in terms of bias and precision. In summary,
      pharmacodynamic analyses are now commonly performed and reported in the oncologic
      literature. The content and format of these analyses has been variable. The goals
      of such analyses are to identify and describe pharmacodynamic relationships and,
      in many cases, to propose a statistical model. However, the appropriateness and
      performance of the proposed model are often difficult to judge. Table 1 displays
      suggestions (in a checklist format) for structuring the presentation of
      pharmacodynamic analyses, which reflect the topics reviewed in this paper.

PMID- 8269583
TI  - Effects of the methoxymorpholino derivative of doxorubicin and its bioactivated
      form versus doxorubicin on human leukemia and lymphoma cell lines and normal bone
      marrow.
AB  - The methoxymorpholino derivative of doxorubicin (MMDX; FCE 23672) has recently
      entered clinical trials because of its broad spectrum of preclinical antitumor
      activity and non-cross-resistance in multidrug-resistant (MDR) tumor models. MMDX
      is activated in the liver to a > 10 times more potent metabolite that cross-links
      DNA. To assess the potential of this drug in hematologic malignancies, we studied
      the myelotoxicity in vitro and antitumor effect of MMDX as well as its
      bioactivated form (MMDX+) in a panel of 14 different human leukemia and lymphoma
      cell lines. The tumor specificity of MMDX in CEM and K562 cells was similar to
      that of doxorubicin (DOX), and that of MMDX+ was slightly superior. All of the 14
      cell lines were found to be more sensitive to MMDX and MMDX+ than were
      granulocyte-macrophage progenitors. On a molar basis, MMDX was approximately 3
      100 times more active than DOX, and MMDX+ was 10-1,000 times more potent than
      DOX. The cytotoxic effect of MMDX and MMDX+ in two P-glycoprotein-positive MDR
      sublines was greatly improved in comparison with that of DOX. Whereas the
      response to DOX in the different leukemia and lymphoma cell lines was highly
      heterogeneous, the response to MMDX and MMDX+ was rather homogeneous. The novel
      anthracycline MMDX and its bioactivated form MMDX+ are highly active against this
      panel of human leukemia and lymphoma cell lines and demonstrate potentially
      greater selectivity for tumor cells in vitro as compared with normal bone marrow
      precursors.

PMID- 8269584
TI  - Identification of vesicle properties that enhance the antitumour activity of
      liposomal vincristine against murine L1210 leukemia.
AB  - The influence of vesicle lipid composition, size and drug-to-lipid ratio on the
      antitumour activity of liposomal vincristine was assessed in the murine L1210
      ascitic leukemia model. A pH gradient-dependent entrapment procedure was used to
      encapsulate vincristine and allowed such vesicle properties to be independently
      varied. Free vincristine delivered i.v. at the maximum tolerated dose (2.0 mg/kg)
      resulted in a 27.8% increase in the life span (ILS) of mice inoculated i.p. with
      L1210 cells. Encapsulation of the drug in egg phosphatidylcholine/cholesterol
      vesicles did not significantly increase the antitumour efficacy of vincristine
      (ILS, 38.9%). In contrast, administration of vincristine entrapped in vesicles
      composed of distearoylphosphatidylcholine (DSPC)/cholesterol resulted in ILS
      values as high as 133%. This enhanced antitumour activity of the DSPC/cholesterol
      formulations was sensitive to the size of the liposomes; increasing the vesicle
      size from 100 nm to 1 micron decreased the ILS from 133.3% to 55.6% at a drug
      dose of 2.0 mg/kg. Decreasing the drug-to-lipid ratio from 0.1:1 to 0.05:1 (w/w)
      had negligible effects on the activity of liposomal vincristine; however, a
      further decrease in the drug-to-lipid ratio to 0.01:1 (w/w) decreased the
      antitumour potency at all drug doses studied. Pharmacology studies indicated that
      the antitumour activities of free and various liposomal forms of vincristine
      correlated well with the residence time of the drug in the circulation. These
      studies indicate that efforts to enhance the therapeutic activity of vincristine
      through liposome encapsulation must address not only the circulation lifetime of
      the vesicle systems but also the capacity of the liposomes to retain entrapped
      drug in vivo.

PMID- 8269585
TI  - Methimazole as a protectant against cisplatin-induced nephrotoxicity using the
      dog as a model.
AB  - The protective effect of methimazole, a commonly used antithyroid drug, on
      cisplatin-induced nephrotoxicity was studied. Eight dogs received 80 mg/m2
      cisplatin i.v. without saline prehydration. Dogs were randomized into two groups
      of four dogs each: one group received 40 mg/kg methimazole i.p. at 30 min prior
      to and 4 h after cisplatin delivery, and the other group received saline placebo
      i.p. Methimazole protected dogs against the in vivo nephrotoxicity elicited by
      cisplatin as evidenced by clinicopathologic and histopathologic indices.
      Protection was not complete, as methimazole-treated animals developed mild
      histopathologic renal changes. Measures of renal oxidative stress did not differ
      between the two groups at day 5 following cisplatin treatment. No difference was
      noted for serum thyroxine concentrations before or after therapy in either group;
      however, serum levels of 3,5,3'-triiodothyronine were significantly higher on day
      5 in both groups of dogs receiving cisplatin, regardless of whether they received
      methimazole or not. Methimazole as used in this study was found to be well
      tolerated in dogs over the short term, with no significant clinical or
      clinicopathologic toxicity being observed. The results of this study support the
      additional evaluation of methimazole as a protectant against cisplatin-induced
      nephrotoxicity using the dog as a model.

PMID- 8269586
TI  - Heat enhances the cytotoxicity of cis-diamminedichloroplatinum(II) and its
      analogues cis-1,1-cyclobutane-dicarboxylato(2R)-2-methyl-1,4-
      butanediammineplatinum(II) and cis-diammine(glycolato)platinum in vitro.
AB  - cis-1,1-Cyclobutanedicarboxylato(2R)-2-methyl-1,4-butanediammin eplatinum(II)
      (NK121) and cis-diammine(glycolato)platinum (254-S), analogues of cis
      diamminedichloroplatinum (II) (CDDP) with reduced nephrotoxicity, are under
      clinical phase trial in Japan. Since CDDP has been shown to be more cytotoxic
      under conditions of an elevated temperature, we tested the cytotoxicity and
      cellular uptake of these analogues at 37 degrees and 43 degrees C using EMT6/KU
      cells in vitro. The cytotoxicity of CDDP was enhanced at 43 degrees C, and that
      of NK121 and 254-S was also enhanced, in a dose- and time-dependent manner. The
      90% cytotoxic concentration (IC90) of each drug was reduced 2.9-fold for CDDP,
      2.5-fold for NK121, and 2.2-fold for 254-S. Cytotoxicity was maximal when the two
      modalities were used simultaneously for all three drugs. The intracellular
      platinum concentration was assayed using flameless atomic absorption
      spectrophotometry. When exposed to IC90 drug concentration at 43 degrees C for 2
      h simultaneously, the intracellular platinum concentration increased to 0.095 +/-
      0.007 micrograms/10(7) cells (a 1.9-fold increase) for CDDP, to 0.198 +/- 0.012
      micrograms/10(7) cells (a 1.3-fold increase) for NK121, and to 0.090 +/- 0.014
      micrograms/10(7) cells (a 1.3-fold increase) for 254-S; respectively, as compared
      with the level measured after drug exposure at 37 degrees C (P < 0.05 for all
      drugs). The elevation in platinum concentration may be one of mechanism related
      to a synergistic effect of the two treatment modalities. The concomitant use of
      CDDP analogues and heat shows potential for possible clinical application.

PMID- 8269587
TI  - Comparative pharmacokinetics of ifosfamide, 4-hydroxyifosfamide,
      chloroacetaldehyde, and 2- and 3-dechloroethylifosfamide in patients on
      fractionated intravenous ifosfamide therapy.
AB  - The initial metabolism of the oxazaphosphorine cytostatic ifosfamide (IF)
      consists of two different pathways: ring oxidation at carbon-4 forms the
      cytostatically active metabolite 4-hydroxyifosfamide (4-OH-IF, "activated
      ifosfamide"), whereas side-chain oxidation with liberation of the presumably
      neurotoxic compound chloroacetaldehyde (CAA) that may also be responsible for IF
      associated nephrotoxicity results in the formation of the cytostatically inactive
      metabolites 2-dechloroethylifosfamide (2-DCE-IF) and 3-dechloroethylifosfamide (3
      DCE-IF). The pharmacokinetics of IF and its metabolites were investigated in 11
      patients with bronchogenic carcinoma receiving IF on a 5-day divided-dose
      schedule (1.5 g/m2 daily). Blood samples were drawn on days 1 and 5 for up to 24
      h after the start of the IF infusion. IF, 2-DCE-IF, and 3-DCE-IF were
      simultaneously quantified by gas chromatography (GC) with an NIP flame-ionization
      detector (NPFID), CAA was determined by GC with an electron-capture detector
      (ECD), and the highly unstable compound 4-OH-IF was measured using a high
      performance liquid chromatography (HPLC) assay with fluorometric detection of 7
      OH-quinoline, which is formed by the condensation of 4-OH-IF-derived acrolein
      with m-aminophenol. As compared with the values obtained on day 1, on day 5 the
      terminal half-life and AUC values determined for IF were reduced by 30% (6.36 vs
      4.06 h and 1781 vs 1204 nmol h ml-1, respectively), whereas the maximal
      concentration (Cmax) values were not affected significantly (199.1 vs 181.1 nmol
      ml-1). This known phenomenon is explained by autoinduction of hepatic IF
      metabolism and was paralleled by increased metabolite levels. The mean Cmax
      values determined for 4-OH-IF, CAA, 3-DCE-IF, and 2-DCE-IF (on day 1/on day 5)
      were 1.51/2.59, 2.69/4.85, 12.9/26.5, and 8.6/16.7 nmol ml-1, respectively. The
      corresponding AUC values were 11.3/16.5, 30.3/34.3, 146/354, and 111/209 nmol h
      ml-1, respectively. As calculated by intraindividual comparison, the mean Cmax
      (day 5): Cmax (day 1) ratios for 4-OH-IF, CAA, 3-DCE-IF, and 2-DCE-IF were 1.94*,
      2.05*, 2.52*, and 2.33*, respectively; the corresponding AUC (day 5): AUC (day 1)
      ratios were 1.51*, 1.29, 2.34*, and 2.23*, respectively (* P < 0.05). These data
      reveal that during fractionated-dose IF therapy the cancerotoxic effect of the
      drug increases. If the assumed role of CAA in IF-associated neurotoxicity and
      nephrotoxicity is a dose-dependent phenomenon, the probability of developing
      these side effects would also increase during prolonged IF application.

PMID- 8269588
TI  - Preclinical activity of a new platinum analogue, lobaplatin, in cisplatin
      sensitive and -resistant human testicular, ovarian, and gastric carcinoma cell
      lines.
AB  - Lobaplatin [1,2-diamminomethylcyclobutane-platinum(II) lactate] is a new platinum
      compound with interesting preclinical activity and apparently no nephro- or
      neurotoxicity that is currently undergoing clinical phase II studies. Little is
      known about the cross-resistance between cisplatin and lobaplatin. The activity
      of this new compound in comparison with cisplatin and carboplatin was evaluated
      in cisplatin-sensitive and cisplatin-resistant human testicular, gastric, and
      ovarian carcinoma cell lines using 96 h continuous drug exposure in a
      sulforhodamine-B assay. In three cisplatin-sensitive testicular carcinoma cell
      lines, lobaplatin and cisplatin showed comparable antitumor activity. The 50%
      growth-inhibitory concentrations (IC50 values) determined for cisplatin ranged
      from 0.1 to 0.4 microM, and those found for lobaplatin ranged from 0.25 to 0.5
      microM. Carboplatin showed markedly lower cytotoxicity in all cell lines tested.
      Lobaplatin was not cross-resistant to cisplatin in a 10-fold cisplatin-resistant
      testicular carcinoma cell line and showed only weak cross-resistance in a 20-fold
      cisplatin-resistant ovarian carcinoma cell line. In contrast, complete cross
      resistance between cisplatin and lobaplatin occurred in two cisplatin-resistant
      human gastric carcinoma cell lines, which were 3.3- and 9-fold resistant to
      cisplatin and 3.1- and 6.5-fold resistant to lobaplatin, respectively.
      Furthermore, lobaplatin showed significant activity against cisplatin-resistant
      human ovarian and testicular carcinoma xenografts in vivo. These data indicate a
      high level of activity for lobaplatin at clinically achievable concentrations in
      ug-sensitive testicular, ovarian, and gastric carcinoma cell lines and a lack of
      complete cross-resistance to cisplatin. Further clinical development of
      lobaplatin is clearly warranted.

PMID- 8269589
TI  - Interaction of the antiemetic metopimazine and anticancer agents with brain
      dopamine D2, 5-hydroxytryptamine3, histamine H1, muscarine cholinergic and alpha
      1-adrenergic receptors.
AB  - The interactions of the antiemetic metopimazine (MPZ) and of the chemotherapeutic
      agents, cisplatin, carboplatin, doxorubicin, etoposide and vincristine were
      investigated at five neurotransmitter receptor binding sites. MPZ had nanomolar
      affinity for alpha 1, dopamine D2 and histamine H1 receptors, weak affinity for
      muscarinic cholinergic receptors, but no affinity for 5-hydroxytryptamine3 (5
      HT3) receptors. Except for vincristine, which showed nanomolar affinity of
      muscarinic cholinergic receptors, none of the chemotherapeutic agents showed
      affinity for any of the receptors investigated at concentrations ranging between
      10(-5) and 10(-7) M. Accordingly, chemotherapy-induced nausea and vomiting seems
      to be mediated by mechanisms other than the direct interaction of cytostatics
      with the neurotransmitter receptors investigated. Our finding that MPZ is without
      affinity for 5-HT3 receptors and therefore seems to mediate its antiemetic effect
      predominantly by dopamine D2 receptor blockade makes it an interesting drug for
      use in combinations with the new class of antiemetics, the 5-HT3 receptor
      antagonists. Data obtained in a recent clinical trial support this observation.

PMID- 8269590
TI  - Effect of hemoglobin solution on the response of intracranial and subcutaneous 9L
      tumors to antitumor alkylating agents.
AB  - The 9L gliosarcoma growing subcutaneously in the hind leg of the Fisher 344 rat
      contains major areas of severe (< 5 mmHg) hypoxia, making up about 49% of the
      tumor. Intravenous administration of an ultrapurified polymerized bovine
      hemoglobin solution (8 ml/kg) along with normal air breathing reduces the
      percentage of severe hypoxia to about 24% and increases oxygenation throughout
      the tumor. Coadministration of the hemoglobin solution increased the tumor growth
      delay of subcutaneously implanted 9L tumors treated with carmustine (BCNU),
      cyclophosphamide, or ifosfamide but did not significantly change the tumor growth
      delay produced by cisplatin (CDDP). Coadministration of the hemoglobin solution
      with each of the four antitumor alkylating agents resulted in a near doubling of
      the percentage of increase in life span in animals bearing intracranial tumors
      treated with the combination as compared with animals treated with the drugs
      alone. Increases in serum blood urea nitrogen (BUN) and creatinine levels in
      treated animals returned to normal by 11 days posttreatment. Major changes in
      liver enzymes occurred with the combination of cyclophosphamide and the
      hemoglobin solution at 4 days posttreatment; however, these values returned to
      the levels in the untreated control animals within 1 week thereafter. These
      results indicate that further exploration of the use of hemoglobin solutions in
      cancer therapy is warranted.

PMID- 8269591
TI  - Isozyme specificity of novel glutathione-S-transferase inhibitors.
AB  - A systematically diversified set of peptide analogs of the reaction product of
      glutathione with an electrophilic substrate have been tested as isozyme-specific
      inhibitors of human glutathione-S-transferase (GST). The potency of the best of
      the inhibitors is in the 0.5 to 20 micromolar range, with kinetics indicative of
      competitive inhibition with glutathione at the active site. The specificity
      observed among three recombinant-derived GST isozymes at both low and high
      potency ranged from negligible to high (at least 20-fold over the next most
      sensitive isozyme). These results define a novel strategy for the design of drugs
      targeting cells with elevated levels of particular GST isozymes, such as tumor
      cells for which elevated levels of GST are believed to be an important cause of
      chemotherapeutic drug resistance.

PMID- 8269592
TI  - Trofosfamide metabolism in different species--ifosfamide is the predominant
      metabolite.
AB  - Trofosfamide (TRO) belongs to the group of oxazaphosphorines and is a congener of
      cyclophosphamide (CYC) and ifosfamide (IFO). The precondition for the cytotoxic
      effect of all oxazaphosphorines is their metabolic activation by "ring" oxidation
      at the hepatic mixed-function oxidase system. In addition, an inactivating
      metabolic pathway ("side chain" oxidation) is known for CYC and IFO. The
      metabolic pattern of the substances gains special interest in the discussion of a
      growing incidence of side effects. Therefore, the in vitro biotransformation of
      TRO was studied. Liver microsomes were prepared from different species, including
      the rat, rabbit, and mouse as well as from one human sample. Microsomal proteins
      were incubated for various periods and concentrations of TRO and its metabolites
      were analyzed by reversed-phase high-performance liquid chromatography (HPLC). In
      vitro metabolism resulted in the formation of activated metabolites by
      hydroxylation at position 4. In addition, side-chain oxidation resulted in the
      formation of IFO and CYC. IFO was the predominating metabolite of this pathway,
      with a 5- to 6-fold excess being noted as compared with CYC in rats and mice. The
      rabbit species showed similar CYC and IFO formation; in the single human sample,
      only IFO could be detected. In rats, the Michaelis constant (Km) for
      biotransformation to IFO was 398 microM, with the maximal volume (Vmax) being
      70.8 nmol 120 min-1 mg protein-1, the corresponding values for biotransformation
      to CYC were 348 microM and 13.30 nmol 120 min-1 mg protein-1. On the basis of its
      structural similarity and the current knowledge of oxazaphosphorine metabolism,
      CYC was expected to be the main metabolite of TRO. The predominance of IFO was
      unexpected, but the observed metabolic profile promises numerous interesting
      aspects for the clinical use of TRO.

PMID- 8269593
TI  - Serotonin involvement in the antitumour and host effects of flavone-8-acetic acid
      and 5,6-dimethylxanthenone-4-acetic acid.
AB  - The relationship of serotonin (5-HT) receptors to the action of the experimental
      antitumour drugs flavone-8-acetic acid (FAA) and 5,6-dimethylxanthenone-4-acetic
      acid (5,6-MeXAA) was studied. Both FAA and 5,6-MeXAA are known to induce the
      synthesis of tumour necrosis factor-alpha (TNF) and to stimulate nitric oxide
      synthesis in vivo, as measured by elevation of plasma nitrate. Serotonin
      potentiated the effect of a subtherapeutic dose of 5,6-MeXAA (20 mg/kg) as
      measured both by plasma nitrate increase and by growth delay of s.c. implanted
      colon 38 tumours. On the other hand, administration of the serotonin 5
      hydroxytryptamine-2 (5-HT2) antagonist cyproheptadine (20 mg/kg) inhibited both
      the plasma nitrate response and, to a lesser extent, the induction of tumour
      haemorrhagic necrosis by 5,6-MeXAA, FAA and TNF. Reduction of circulating plasma
      serotonin by pre-treatment with p-chlorophenylalanine and reserpine reduced the
      plasma nitrate response, but not the tumour necrosis response, to 5,6-MeXAA (30
      mg/kg). It is suggested that serotonin is necessary for the induction of nitric
      oxide synthases and acts, either directly or indirectly, in concert with TNF.
      Serotonin agonists may have utility in increasing nitric oxide synthesis in
      response to TNF or to agents that induce TNF as part of their antitumour action.

PMID- 8269594
TI  - Impact of omeprazole on the plasma clearance of methotrexate.
AB  - Omeprazole inhibits the gastric hydrogen pump and is an effective treatment for
      peptic ulcers. Methotrexate is a chemotherapeutic agent that inhibits
      dihydrofolate reductase and is eliminated by a hydrogen-ion-dependent mechanism
      in the kidney. We present evidence that omeprazole inhibits methotrexate
      clearance and may result in potentially toxic methotrexate levels.

PMID- 8269595
TI  - Severe depletion of cellular thiols and glutathione-related enzymes of a
      carmustine-resistant L1210 strain associates with collateral sensitivity to
      cyclophosphamide.
AB  - Cyclophosphamide (CPA) increased the life span of both carmustine (BCNU)
      resistant (L1210/BCNU) and BCNU-sensitive L1210 (L1210/0) leukaemic mice; their
      sensitivity to CPA, however, was extremely different. The BCNU-resistant strain
      was much more sensitive (collaterally) to CPA than was its sensitive counterpart.
      The collateral sensitivity was accompanied by a severe reduction in the activity
      of glutathione-related enzymes and in protein thiol (SH) and non-protein SH
      levels in BCNU-resistant cells. The activity of glutathione reductase (GSSG-R)
      was 2 times higher in the L1210/0 cells than in the L1210/BCNU cells. Glutathione
      S-transferase (GST) was also almost 2 times more active in the sensitive cells
      than in the resistant strain. To develop resistance against CPA with a single
      treatment (60 mg/kg) per passage, the L1210/BCNU strain needed 26 passages,
      whereas the L1210/0 strain required significantly fewer. The resistance developed
      against CPA was associated with a moderate elevation of thiols in the L1210/CPA
      cells, whereas this elevation was approximately 3 times more pronounced in the
      L1210/BCNU/CPA cells. The severely reduced activity of GST in the L1210/BCNU
      strain was markedly increased when these cells were made resistant to CPA; the
      GSSG-R activity, however, remained low, suggesting an irreversible injury of this
      enzyme by BCNU.

PMID- 8269596
TI  - Bryostatin 1 induces productive Epstein-Barr virus replication in latently
      infected cells: implications for use in immunocompromised patients.
AB  - Bryostatin 1 is a novel anti-tumor agent currently undergoing clinical trial. We
      investigated the effect of this drug on B-lymphocyte cell lines that carry the
      Epstein-Barr virus and found that it induces these latently infected cells into
      the production of transforming virus particles over a wide range of
      concentrations. These results may have clinical implications, particularly with
      regard to the use of the drug in the immunocompromised patient.

PMID- 8269597
TI  - Influence of prophylactic anticonvulsant therapy on high-dose busulphan kinetics.
AB  - The pharmacokinetics of high-dose busulphan was studied in 17 patients during
      conditioning prior to bone marrow transplantation using deuterium-labeled
      busulphan (d8-BU). About 50% of busulphan doses 1 and 16 was replaced with d8-BU.
      Patients were treated with phenytoin or diazepam as prophylactic anticonvulsant
      therapy. Patients who received phenytoin demonstrated significantly higher
      clearance (mean +/- SD, 3.32 +/- 0.99 ml min-1 kg-1), a lower area under the
      concentration-time curve (AUC, 5,412 +/- 1,534 ng h ml-1; corrected for
      dose/kilogram) and a shorter elimination half-life (3.03 +/- 0.57 h) for the last
      dose of d8-BU (dose 16) as compared with the first dose (2.80 +/- 0.78 ml min-1
      kg-1, 6,475 +/- 2,223 ng h ml-1 and 3.94 +/- 1.10 h, respectively). No difference
      in the above mentioned pharmacokinetic parameters was seen in patients treated
      with diazepam. Moreover, a continuous decrease in the steady-state level of
      busulphan was observed in four of seven patients in the phenytoin-treated group,
      whereas in the diazepam group, such a decrease was seen in only one of eight
      patients. We conclude that phenytoin used as prophylactic anticonvulsant therapy
      alters busulphan pharmacokinetics and, most probably, its pharmacodynamics. For
      adequate prophylactic therapy, anticonvulsants with fewer enzyme-inductive
      properties than phenytoin should be used.

PMID- 8269598
TI  - Extended-release formulation of morphine for subcutaneous administration.
AB  - Pain arising from cancer tends to be chronic and chemotherapy of cancer pain
      usually requires narcotics. Most injectable narcotics, however, have short half
      lives (T1/2) and require either continuous infusion or repeated frequent
      injections which are both inconvenient and uncomfortable. An extended-release
      formulation of morphine sulfate (Depo/Morphine) in a lipid-based drug-delivery
      system was characterized and tested in an animal model. The encapsulation
      efficiency was 53% +/- 4%, and the in vitro release T1/2 in human plasma at 37
      degrees C was 12.1 +/- 1.1 days. Following s.c. administration of Depo/Morphine,
      the total amount of morphine remaining at the s.c. injection site decreased
      monoexponentially with a T1/2 value of 2.59 +/- 0.16 days as compared with 0.46
      +/- 0.04 h following the injection of unencapsulated morphine. The morphine
      concentration in plasma also decreased monoexponentially with a T1/2 value of
      8.33 +/- 2.13 days as compared with 0.45 +/- 0.21 h for unencapsulated morphine.
      Cataleptic behavior was observed in mice injected with unencapsulated morphine
      but not in those given an identical dose of morphine in the form of
      Depo/Morphine. In conclusion, Depo/Morphine has potential as an extended-release
      formulation of morphine and may be useful in chemotherapy of cancer pain as well
      as in maintenance therapy of narcotic addicts.

PMID- 8269599
TI  - The role of reduced nicotinamide adenine dinucleotide phosphate in glucose- and
      temperature-dependent doxorubicin cytotoxicity.
AB  - The mechanism of doxorubicin resistance induced by glucose deprivation was
      examined using an L929 cell system. Resistance developed even when the synthesis
      of glucose-regulated proteins was suppressed by supplementing glucose-deprived
      cultures with uridine. Resistance was also not correlated with pyruvate
      availability, with DNA strand breaks, or with intracellular drug or nucleotide
      levels. However, intracellular concentrations of reduced nicotinamide adenine
      dinucleotide phosphate (NADPH) decreased to undetectable levels in glucose
      deprived cells with or without uridine supplementation. NADPH depletion induced
      by treating glucose-fed cells with low concentrations of methylene blue afforded
      the same degree of protection as glucose deprivation, and normal sensitivity
      could be restored to glucose-deprived cells by adding NADPH to the culture
      medium. These results suggest that decreased NADPH availability is responsible
      for the doxorubicin resistance induced by glucose deprivation. Although drug
      uptake and NADPH production increased with temperature, these effects could not
      fully account for the > 1000-fold decrease in clonogenic survival observed over
      the 25 degrees-37 degrees C temperature range. Similarly, manipulation of NADPH
      levels confirmed a role for drug bioreduction in the cytotoxic mechanism but did
      not suggest that NADPH availability was rate-limiting for this process at any
      temperature employed.

PMID- 8269600
TI  - Preclinical pharmacology of the antitumor agent O-6-methylguanine in CDF1 mice.
AB  - O-6-methylguanine (O6-mG), a guanine analog recently shown to be a potent
      inhibitor of alkylguanine-DNA alkyltransferase, has been found to potentiate the
      antitumor activity of nitrosoureas, in particular, carmustine (BCNU), in
      resistant cell lines (HT-29 mer+) and is targeted for development as a modulating
      agent with chloroethyl nitrosoureas. A high-performance liquid chromatography
      (HPLC) assay of O6-mG in plasma has been developed using a microC18 reverse-phase
      column. O6-mG and the internal standard deoxyguanosine (dGuo) were eluted with a
      linear gradient of from 15% to 35% methanol in 0.5 M ammonium acetate (pH 6.5) at
      a flow rate of 1 ml/min. The assay was linear over a 4-log concentration range
      with a detection limit of 0.1 microgram/ml. The within-run and between-run
      coefficients of variation (CV) were found to be 8.1% and 9.3%, respectively. The
      pharmacokinetics (PK) of O6-mG were investigated in healthy CDF1 mice following
      separate i.v. and i.p. administrations. At 20 mg/kg i.v., plasma O6-mG gave a
      biexponential profile with a terminal half-life (t1/2) of 24 min and a total
      clearance (CLT) of 23.7 ml min-1 kg-1. Higher doses (40-80 mg/kg) revealed a
      fluctuating third phase, probably due to enterohepatic cycling. Dose-dependent
      kinetics as measured by CLT and area under the plasma-concentration curve (AUC)
      values were also seen. Following i.p. dosing, O6-mG was completely absorbed and
      available to the circulation. No acute toxicity was observed in the animals,
      except for mild sedation, a possible side effect of the 10% ethanol used in the
      formulation. Studies on the cellular metabolism of highly purified [3H]-O6-mG
      have shown that the compound is not anabolized by a human lymphoblastoid cell
      line (CEM). Biochemistry studies have shown that the parent molecule is
      inactivating the alkylguanine-DNA alkyltransferase (AGT), thus exerting its
      pharmacological effect.

PMID- 8269601
TI  - Escalating doses of interferon alpha-2A with cisplatin and concomitant
      radiotherapy: a phase I study.
AB  - In this phase I study, we added escalating doses of interferon-alpha 2A (IFN) to
      cisplatin and twice-daily radiotherapy based on the following rationale.
      Radiation enhancement has been shown for both interferon and cisplatin; in
      addition, potentiation of the cytotoxic activity of cisplatin by interferon has
      been demonstrated. A total of 48 patients with advanced solid tumors were treated
      with radiotherapy in 2 daily fractions of 125 cGy plus cisplatin at 8-10 mg/m2
      per day delivered on 3 different schedules (continuous infusion, daily short-term
      infusion, and single short-term infusion of 50 mg/m2). IFN was injected s.c. 2 h
      preceding the first daily fraction of radiation. IFN doses ranged from 0 to 5.0 x
      10(6) U/m2 per day. All therapy was given over 5 days of every other week until
      completion of the radiotherapy. Treatment at all dose levels was well tolerated
      during cycles 1 and 2, with no instance of acute grade 3 or 4 toxicity being
      noted. However, cumulative myelosuppression in patients receiving more than two
      treatment cycles was seen at all dose levels and was attributed to the repeated
      administration of cisplatin. Alteration of the cisplatin schedule did not allow
      for further dose escalation of cisplatin. Our recommended doses are cisplatin
      given at 8 mg/m2 per day as a continuous infusion with IFN at 5.0 x 10(6) U/m2
      per day. Among 24 patients with non-small-cell lung cancer, 2 had a complete
      response, 9 had a partial response, and 7 had stable disease. We conclude that
      this concomitant cisplatin-IFN-radiotherapy regimen is feasible. Activity was
      seen in non-small-cell lung cancer, and further studies of this regimen in that
      disease appear indicated.

PMID- 8269602
TI  - Differential cytotoxicity of buthionine sulfoximine to "normal" and transformed
      human lung fibroblast cells.
AB  - Glutathione (GSH) depletion has been studied extensively as a possible means to
      sensitive tumor cells to radiation treatment and chemotherapy. The present study
      was undertaken to compare the cytotoxicity of GSH depletion in normal and
      transformed cells. The results showed that specific inhibition of GSH synthesis
      by L-buthionine sulfoximine (BSO) caused significantly higher cytotoxicity in
      "normal" human-lung fibroblast cells than in their transformed counterparts. This
      finding suggests a possibility that depletion of GSH could be more harmful to
      normal cells than to transformed and/or tumor cells and that the selective
      cytotoxicity of BSO to normal cells could limit its potential as an effective
      sensitizer for cancer treatment.

PMID- 8269603
TI  - Phase I study of 5-fluorouracil and leucovorin by a 14-day circadian infusion in
      metastatic adenocarcinoma patients.
AB  - Initial experimental and clinical studies have indicated that 5-fluorouracil (5
      FU) toxicity can be reduced by delivering 5-FU at around 4 a.m. More recent data
      have suggested that the toxicity might be reduced even more with delivery at
      around 9-10 p.m. The current study determined the maximum tolerated dose (MTD)
      for 5-FU and leucovorin (LV) delivered as a continuous circadian infusion over 14
      days every 28 days, with the peak of the infusion occurring at around 3-4 a.m.
      The peak drug delivery was shifted to 9-10 p.m. in all patients developing
      toxicity of > or = grade II (Eastern Cooperative Oncology Group) to determine if
      this timing further reduced toxicity and enabled increased dose intensity. A
      total of 14 patients with metastatic adenocarcinoma received an admixture of 5-FU
      and LV via a programmable portable infusion pump, with 62.5% of the 24-h dose
      being given over 7 h around the infusion peak. The starting dose level of 5-FU
      (200 mg/m2 daily) and LV (5 mg/m2 daily) was that established as the highest
      tolerable dose rate in a previously reported phase I study using a 14-day flat
      infusion of 5-FU and LV. The LV dose was first escalated to 20 mg/m2 daily,
      followed by escalations of the 5-FU dose. A total of 51 courses were evaluable
      for toxicity. The dose-limiting toxicity was oral mucositis and hand-foot
      syndrome. More dose intensity could be delivered using a circadian infusion
      peaking at around 3-4 a.m. than was possible with a flat infusion of these drugs.
      Toxicity was reduced even further with peak drug delivery at around 9-10 p.m. The
      recommended dose for phase II studies using this schedule is 250 mg/m2 5-FU daily
      and 20 mg/m2 LV daily with the peak of the infusion occurring at 9-10 p.m. This
      is a 300% and 25% higher dose for LV and 5-FU, respectively, than was found to be
      safe for a flat infusion.

PMID- 8269604
TI  - beta-cyclodextrin tetradecasulfate/tetrahydrocortisol +/- minocycline as
      modulators of cancer therapies in vitro and in vivo against primary and
      metastatic Lewis lung carcinoma.
AB  - Tetrahydrocortisol, beta-cyclodextrin tetradecasulfate, and minocycline used
      alone or in combination are not very cytotoxic toward EMT-6 mouse mammary tumor
      cells growing in monolayer. Tetrahydrocortisol (100 microM, 24 h) and beta
      cyclodextrin tetradecasulfate (100 microM, 24 h) protected EMT-6 cells from the
      cytotoxicity of CDDP, melphalan, 4-hydroperoxycyclophosphamide, BCNU, and X-rays
      under various conditions of oxygenation and pH. Minocycline (100 microM, 24 h)
      either had no effect upon or was additive with the antitumor alkylating agents or
      X-rays in cytotoxic activity toward the EMT-6 cells in culture. The combination
      of the three modulators either had no effect upon or was to a small degree
      protective against the cytotoxicity of the antitumor alkylating agents or X-rays.
      The Lewis lung carcinoma was chosen for primary tumor growth-delay studies and
      tumor lung-metastases studied. Tetrahydrocortisol and beta-cyclodextrin
      tetradecasulfate were given in a 1:1 molar ratio by continuous infusion over 14
      days, and minocycline was given i.p. over 14 days, from day 4 to day 18 post
      tumor implantation. The combination of tetrahydrocortisol/beta-cyclodextrin
      tetradecasulfate diminished the tumor growth delay induced by CDDP and melphalan
      and produced modest increases in the tumor growth delay produced by
      cyclophosphamide and radiation. Minocycline co-treatment increased the tumor
      growth delay produced by CDDP, melphalan, radiation, bleomycin, and, especially
      cyclophosphamide, where 4 of 12 animals receiving minocycline (14 x 5 mg/kg, days
      4-18) and cyclophosphamide (3 x 150 mg/kg, days 7, 9, 11) were long-term
      survivors. The 3 modulators given in combination produced further increases in
      tumor growth delay with all of the cytotoxic therapies, and 5 of 12 of the
      animals treated with the 3-modulator combination and cyclophosphamide were long
      term survivors. Although neither tetrahydrocortisol/beta-cyclodextrin
      tetradecasulfate, minocycline, nor the three modulator combination impacted the
      number of lung metastases, there was a decrease in the number of large lung
      metastases. Treatment with the cytotoxic therapies alone reduced the number of
      lung metastases. Addition of the modulators to treatment with the cytotoxic
      therapies resulted in a further reduction in the number of lung metastases. These
      results indicate that agents that inhibit the breakdown of the extracellular
      matrix can be useful additions to the treatment of solid tumors.

PMID- 8269605
TI  - Covalent modification of DNA by daunorubicin.
AB  - Daunorubicin, a clinically useful antitumor agent, induces mammary adenocarcinoma
      in Sprague-Dawley rats. As part of an investigation of the mechanism of tumor
      induction by daunorubicin, the formation of daunorubicin-DNA adducts has been
      investigated by 32P-postlabeling assay. Rat-liver DNA incubated with either 0.05
      or 0.1 mM daunorubicin, rat-liver microsomes, and 5 mM reduced nicotinamide
      adenine dinucleotide phosphate (NADPH) for 1 h contained covalent DNA adducts in
      addition to the endogenous adduct profile present in control DNA. With 1.5 mM
      cumene hydroperoxide serving as a cofactor, higher levels of these two adducts
      and two additional adducts were formed, all of which most likely were
      daunorubicin-DNA adducts. This latter treatment also resulted in an
      intensification of three endogenous DNA modifications over levels occurring in
      control DNA. Covalent DNA alterations in vivo were studied in rats treated with
      20 mg/kg daunorubicin for 2 days and 200 mg/kg on the 3rd day. Daunorubicin-DNA
      adducts as observed in vitro could not be detected in DNA of liver or mammary
      epithelial cells. The levels of endogenous modifications in drug-treated rats
      were increased by 200% in mammary DNA and by 50% in hepatic DNA as compared with
      controls. It was concluded from these experiments that daunorubicin may be
      metabolically activated to a reactive metabolite that binds covalently to DNA.
      These daunorubicin-DNA adducts may not play a role in tumor induction because
      they were not detectable in vivo. However, the increase in levels of endogenous
      DNA modifications induced by daunorubicin both in vitro and in vivo is consistent
      with a role of this class of DNA modification in the carcinogenic process.

PMID- 8269606
TI  - Schedule-dependent synergism of edatrexate and cisplatin in combination in the
      A549 lung-cancer cell line as assessed by median-effect analysis.
AB  - The methotrexate analog edatrexate has been shown to have greater antitumor
      activity and an improved therapeutic index as compared with its parent compound
      in preclinical systems. These studies suggest that edatrexate may have a broad
      role in the treatment of solid tumors. Information regarding edatrexate in
      combination with other chemotherapeutic agents is limited. We evaluated the
      interaction of edatrexate with cisplatin in vitro as assessed by median-effect
      analysis in the A549 human lung-cancer cell line. The effects of dose, exposure
      time, and schedule dependence were assessed. Cytotoxicity was evaluated using the
      tetrazolium-based colorimetric (MTT) assay. The inhibitory concentration
      producing 50% absorbance (IC50 for edatrexate with 1 h exposure was 1.4 microM.
      For all combination experiments, the edatrexate dose was fixed at 0.2 microM
      (IC10) whereas cisplatin (CDDP) concentrations were varied for 1-, 3-, and 24-h
      exposures either before or after edatrexate treatment. Drug interactions were
      assessed using the combination-index method as defined by median-effect analysis.
      A synergistic interaction was documented in experiments when edatrexate was
      applied prior to CDDP (combination index, < 1). The combination studies in which
      edatrexate was used prior to CDDP resulted in significant reduction of all three
      CDDP IC50 values: 1-h IC50, from 30.0 to 3.9 microM; 3-h IC50, from 21.3 to 1.4
      microM; and 24-h IC50, from 1.7 to 0.03 microM. In contrast, synergism was not
      observed in experiments in which edatrexate treatment occurred after cisplatin
      exposure. Median-effect analysis is a useful method of determining drug
      interactions. In the present study, the combination of edatrexate and CDDP
      demonstrated schedule-dependent synergism, with the synergism being observed only
      in the setting of edatrexate treatment before CDDP exposure. Due to the potential
      broad spectrum of activity of edatrexate plus CDDP, further studies are warranted
      to determine the mechanism responsible for the synergism and to investigate this
      combination in a variety of tumor models.

PMID- 8269608
TI  - Pharmacokinetics of an extended-release human interferon alpha-2b formulation.
AB  - The in vivo half-life of human interferon alpha-2b (hIFN-alpha-2b) is relatively
      short, and frequent injections over prolonged periods are required for efficacy.
      An extended-release formulation of hIFN-alpha-2b (Depo/IFN) was created by
      encapsulation into a lipid-based drug-delivery system. The capture efficiency was
      51% +/- 13% and the release half-life in human plasma at 37 degrees C was 16
      days. The pharmacokinetics of Depo/IFN was compared with that of unencapsulated
      standard hIFN-alpha-2b (Std/IFN) in the peritoneal cavity of male BDF1 mice.
      Depo/IFN exhibited a 13-fold longer intraperitoneal (i.p.) half-life as compared
      with Std/IFN (20 vs 1.5 h). The release of free hIFN-alpha-2b from Depo/IFN into
      the peritoneal cavity was slow and protracted, with a 10-fold lower peak
      concentration and a 13-fold longer apparent half-life being observed in
      comparison with Std/IFN. The areas under the curve of free hIFN-alpha-2b in the
      peritoneal cavity were comparable for Depo/IFN and Std/IFN. hIFN-alpha-2b was
      detectable in plasma only after the i.p. administration of Std/IFN. These data
      suggest the possibility that Depo/IFN may be useful as an extended-release
      formulation of hIFN-alpha-2b.

PMID- 8269607
TI  - Increased doxorubicin levels in hepatic tumors with reduced systemic drug
      exposure achieved with complete hepatic venous isolation and extracorporeal
      chemofiltration.
AB  - We evaluated a novel system of complete hepatic venous isolation and
      chemofiltration (CHVI-CF) to reduce systemic drug exposure following regional
      hepatic infusion of doxorubicin. Rabbits bearing hepatic VX-2 tumors were given
      doxorubicin via either hepatic arterial infusion (HAI) or portal venous infusion
      (PVI). A dual-balloon vena cava catheter and extracorporeal chemofilter were used
      to capture and filter hepatic venous blood in experimental animals. Control
      animals received chemotherapy without hepatic venous isolation and
      chemofiltration. Following a 5-min HAI of doxorubicin (3 or 5 mg/kg), control and
      experimental animals had similar doxorubicin levels in their livers and VX-2
      tumors, but experimental animals showed a significant reduction in doxorubicin
      levels in systemic plasma, heart, and kidney tissue as compared with control
      animals (P < 0.01). HAI produced a 4-fold increase in doxorubicin levels in VX-2
      tumors as compared with the drug levels obtained using PVI (P < 0.01). A single
      HAI of 3 mg/kg doxorubicin in animals treated with CHVI-CF produced marked tumor
      necrosis at 7 and 14 days after treatment. By increasing the total body clearance
      of doxorubicin, this system will allow HAI of higher doses of drug in attempts to
      improve the antitumor response.

PMID- 8269609
TI  - Proteinuria due to suboptimal hydration with high-dose methotrexate therapy.
AB  - One of the major complications after high-dose methotrexate (HDMTX) infusions is
      renal damage. We investigated the occurrence of proteinuria after HDMTX
      administration in children with pediatric malignancies (acute lymphoid leukaemia,
      osteosarcoma Burkitt's lymphoma). In the period 1989-1990 we gave 52 HDMTX
      courses to 24 children. During this period, prehydration and extra urinary
      alkalisation were performed only if the urinary specific gravity was over 1010 or
      if the urinary pH fell below 7. Using this schedule the mean values obtained for
      protein extraction were: before the therapy, 0.12 +/- 0.03 g/m2; on day 1 after
      MTX treatment, 0.38 +/- 0.06 g/m2; and on day 2 after the MTX infusion, 0.39 +/-
      0.11 g/m2 (P < 0.01). A significant increase in proteinuria (> 0.2 g/m2 post- vs
      pretreatment) was detectable in 54% of the patients. In the period 1991-1992 we
      modified the hydration-alkalisation schedule to include i.v. prehydration for 18
      24 h at 3 l/m2/day with a 0.45% NaCl-5% glucose solution along with sodium
      bicarbonate and posthydration for 72 h with the same solution. On this protocol
      the mean values determined for the urinary protein content were all in the normal
      range (pretreatment, 0.03 g/m2/day; day 1, 0.05 g/m2/day; and day 2, 0.08
      g/m2/day). These findings were significantly different from the previous results
      (P < 0.05).

PMID- 8269610
TI  - Elevation of serum phase II enzymes by anticarcinogenic enzyme inducers: markers
      for a chemoprotected state?
AB  - Inducers of Phase II enzymes, already consumed by humans as food additives,
      medicines or as constituents of vegetables, can prevent experimental
      carcinogenesis. Since protection is neither carcinogen- nor organ-specific,
      clinical trials are already underway to establish the efficacy of
      'anticarcinogenic enzyme inducers' (i.e. oltipraz). However, efficient and cost
      effective assays to establish the dose wherein a putative anticarcinogen can
      raise Phase II enzyme levels are lacking. We tested the proposal that serum Phase
      II enzyme activities would be dependent on relative tissue levels by measuring
      quinone reductase and glutathione S-transferase activities in sera of mice
      treated with dietary 2(3)-tert-butyl-4-hydroxyanisole (BHA) or dimethyl fumarate.
      Serum activities were significantly elevated in animals with increased tissue
      specific activities of these Phase II enzymes. Increasing concentrations of BHA
      in the diet from 0.05-0.5% increased hepatic specific activities of both QR and
      GST from two to six-fold, and increases in serum activities were well correlated
      to increases observed in the liver (r2 > or = 0.95). There was no evidence for an
      elevation of serum alanine aminotransferase levels. Thus, in the absence of
      serological evidence for hepatocellular damage, increased serum Phase II enzyme
      activities can be correlated to tissue levels. Our results suggest that similar
      assays tailored to human sera will not only be useful in the execution of
      chemoprevention trials, but also to assess the role that Phase II enzyme
      induction plays in the prevention of cancer by fruits and vegetables.

PMID- 8269611
TI  - Different stability of AP1 proteins in human keratinocyte and fibroblast cells:
      possible role in the cell-type specific expression of human papillomavirus type
      18 genes.
AB  - Human papillomaviruses (HPV) replicate in keratinocyte but not fibroblast cells.
      Several factors, including AP1 (Jun/Fos), contribute to the cell-type specific
      transcription of HPV genes. The binding of AP1 upstream of the HPV type 18 early
      gene E6 is essential for transcription of the early genes. Here we show that AP1
      levels are low in early passage human fibroblast extracts. In contrast, human
      keratinocyte extracts contain high levels of AP1. In agreement with this, in vivo
      an AP1-dependent promoter is more active in keratinocytes than in fibroblasts.
      Pulse chase experiments indicated that Jun and Fos are relatively stable in human
      keratinocyte cells after serum induction, whereas in early passage human
      fibroblasts they are rapidly broken down. Nuclear extracts of these fibroblasts
      contain a cysteine proteinase which can degrade AP1. Furthermore, the activity of
      a cathepsin B-like cysteine proteinase is elevated in these human fibroblast
      extracts relative to other cell types. Interestingly, after several passages in
      culture the fibroblasts lose this proteinase activity and the amount of AP1
      increases. Taken together, these results suggest that the quantitative difference
      in AP1 proteins between human keratinocytes and fibroblasts is due to a
      difference in protein stability. The cathepsin B-like cysteine proteinase is a
      candidate for a role in the unusually rapid breakdown of AP1 in early passage
      human fibroblast cells. Low levels of AP1 in the fibroblasts correlate with the
      low activity of AP1-dependent promoters, like that of HPV-18, in these cells.

PMID- 8269612
TI  - Activation of the food derived carcinogen 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline by rat pleural cavity inflammatory cells.
AB  - There is an increased risk of developing neoplastic disease at sites of chronic
      inflammation. We have used a model of rat pleural cavity inflammation induced
      with carrageenan to obtain inflammatory cells comprising predominantly phagocytes
      (macrophages, monocytes and neutrophils) to examine their ability to activate
      chemical carcinogens. Treatment of these cells with phorbol-12-myristate-13
      acetate (PMA, 15 mM) to stimulate respiratory burst, resulted in a rapid release
      of reactive oxygen species. Incubation of the cooked food promutagen 2-amino-3,8
      dimethylimadazo-[4,5-f]quinoxaline (MeIQx) with PMA (or phorbol dibutyrate or
      opsonised zymosan or silica) stimulated pleural cavity phagocytes, generated
      highly electrophilic products which were mutagenic in an Ames Salmonella
      mutagenicity assay. whereas resting cells (no PMA) had negligible activity.
      Mutagenic activation of MeIQx by PMA stimulated cells could be reduced by
      inhibitors of active oxygen such as mannitol, benzoate, dimethyl sulphoxide,
      superoxide dismutase and catalase and by inhibition of myeloperoxidase activity.
      In contrast the very potent, broad spectrum cytochrome P450 inhibitor 8
      methoxypsoralen had no effect, suggesting the reaction was not cytochrome P450
      dependent. Activation of MeIQx by PMA stimulated cells could be abolished by the
      protein kinase C inhibitor staurosporin, confirming the importance of protein
      kinase C in the reaction. Furthermore, performing incubations in the presence of
      fluoride (10 mM) to directly stimulate adenylyl cyclase avoided the requirement
      for phorbol ester in the activation process. These data show that phagocytes
      stimulated to release active oxygen species can activate MeIQx to a mutagenic
      derivative. Mutagenic activation of MeIQx in this system was dependent upon the
      generation of active oxygen via signal transduction pathways involving protein
      kinase C and adenylyl cyclase. We suggest that the mechanism of MeIQx activation
      by phagocytes probably involves one electron oxidation mediated by active oxygen
      species.

PMID- 8269613
TI  - Recoveries of DNA adducts of polycyclic aromatic hydrocarbons in the 32P
      postlabelling assay.
AB  - The 32P-postlabelling assay for analysis of DNA adducts of chemical carcinogens
      has been applied in a large number of experimental animal and human studies. Most
      human studies have dealt with occupational and environmental exposures to
      polycyclic aromatic hydrocarbons (PAHs). The postlabelling assay does not allow
      direct chemical identification, and most studies with this method have not been
      performed in a quantitative way. Very little is therefore known about the
      identity and absolute levels of adducts, which are important contributors to the
      process of risk identification and quantitation. In the present study it was,
      therefore, decided to test some parameters suspected to affect recoveries of
      adducts in the phosphorylation step of the assay. For this purpose 12 different
      PAHs were reacted individually and in a mixture with DNA in the presence of a rat
      liver S9 metabolizing system. Different concentrations of ATP, calcium chloride
      and polynucleotide kinase were tested using the nuclease P1 enhancement. We found
      that each factor contributed to adduct recovery and that optimal conditions could
      be defined. Diluting the modified DNA samples up to 1000 times had little
      influence on the recoveries of adducts. Comparing the nuclease P1 and the butanol
      extraction procedures for adduct purification showed that both methods gave
      similar patterns and levels of major adducts. The absolute recoveries in
      postlabelling, based on 3H-binding of radiolabelled compounds, were for most of
      the tested compounds relatively low. The fact that the nuclease P1 and the
      butanol extraction procedures gave similar recoveries points towards common
      factor(s) involved in the reduction of the recovered adduct levels. Based on the
      observed recoveries the conclusion can be drawn that when postlabelling related
      adducts in human samples the true total adduct levels can be considerably
      underestimated, even if optimal conditions are used.

PMID- 8269614
TI  - Increased CYP1A2 content and capacity to activate Glu-P-1 and Trp-P-2 in liver
      microsomes of scorbutic ODS rats.
AB  - Osteogenic Disorder Shionogi (ODS) rats, which cannot synthesize ascorbic acid
      due to a deficiency of L-gulonolactone oxidase, become scorbutic when not
      supplied with dietary ascorbic acid. We used the deficient rats to study the
      effects of ascorbic acid on the amount of cytochrome P450 enzymes in liver
      microsomes. The total amount of hepatic cytochrome P450 in ODS rats deprived of
      ascorbic acid was lower by approximately 40%, whereas ODS rats fed with ascorbic
      acid and the wild strain had the same level of total hepatic cytochrome P450.
      Western blot analysis for various forms of cytochrome P450 in liver microsomes
      indicated that the amount of CYP1A2 was significantly higher in ascorbic acid
      deficient rats. On the other hand, amounts of CYP2B2 and 3A were lower, and those
      of CYP2E1 and CYP2C6/11 were unaffected. In accordance with the higher amount of
      CYP1A2, Northern blot analysis showed increased expression of CYP1A2 mRNA. The
      capacity of microsomes to produce mutagens from 2-amino-6-methyl-dipyrido[1,2
      a:3',2'-d]imidazole acetate (Glu-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole
      acetate (Trp-P-2) was higher in scorbutic ODS rats by the Ames test. These
      results indicate that the effects of ascorbic acid deficiency on the expression
      of cytochrome P450 in ODS rat livers are form-specific and that the increased
      CYP1A2 is associated with increased metabolic activation of promutagens in the
      scorbutic state.

PMID- 8269615
TI  - Benzene and phenol metabolism by mouse and rat liver microsomes.
AB  - Benzene, an important industrial solvent and constituent of unleaded gasoline,
      causes leukemia and aplastic anemia in humans. Mice are more sensitive than rats
      to benzene toxicity, though neither species has been shown to respond
      consistently with benzene-induced leukemia. Benzene biotransformation in liver to
      phenol, hydroquinone, catechol and/or muconaldehyde is thought to be necessary
      for its hematotoxicity and/or genotoxicity. Our goal is to develop a mathematical
      simulation model capable of describing the pathways and kinetics of benzene
      metabolism by rat and mouse liver microsomes and to assess the role of species
      metabolic differences in species sensitivity. Microsomes were incubated with 4
      microM [U-14C]-benzene or 4 microM [U-14C]phenol. Metabolite production was
      quantified by extraction into ethyl acetate, HPLC separation and liquid
      scintillation spectroscopy. After 45 min, mouse liver microsomes converted 20% of
      the benzene to phenol, 31% to hydroquinone and 2% to catechol. Rat liver
      microsomes converted 23% of benzene to phenol, 8% to hydroquinone and 0.5% to
      catechol. Production of hydroquinone and catechol continued for 90 min for mouse
      liver microsomes, while production by rat liver microsomes had virtually ceased
      by 90 min. Muconic acid production by mouse liver microsomes was < 0.2% and <
      0.04% from benzene and phenol respectively after 90 min. A quantitative
      simulation model was constructed to describe the in vitro metabolism of benzene,
      incorporating the reaction sequences: benzene-->phenol-->catechol-
      >trihydroxybenzene and phenol-->hydroquinone-->trihydroxybenzene. In the model,
      all of the reaction steps are assumed to be catalyzed by the same enzyme(s),
      cytochrome(s) P450, and benzene, phenol, hydroquinone and catechol in solution
      are all assumed to compete, through reversible binding, for the same reaction
      site(s) on cytochrome(s) P450. The simulation model accurately described both the
      benzene and phenol kinetic data, supporting this proposed mechanism. In
      particular, this model suggests that the observed inhibition of benzene on phenol
      metabolism, and of phenol on benzene metabolism, occurs through competition for a
      common reaction site, which can also bind catechol and hydroquinone.

PMID- 8269616
TI  - Cellular and chromosomal hypersensitivity to DNA crosslinking agents and
      topoisomerase inhibitors in the radiosensitive Chinese hamster irs mutants:
      phenotypic similarities to ataxia telangiectasia and Fanconi's anaemia cells.
AB  - The mutants irs1, irs2 and irs3 were previously isolated from the Chinese hamster
      line V79-4 on the basis of their hypersensitivity (2-3-fold) to cell inactivation
      by X-rays. Here the cross-sensitivities of the irs mutants to an array of
      chemical mutagens and topoisomerase inhibitors was determined in a differential
      cytotoxicity assay. Irs2 showed moderate hypersensitivity (2-3-fold) to simple
      alkylating agents and oxidative mutagens but was most sensitive (8-fold) to the
      topisomerase I inhibitor camptothecin. In contrast irs2 showed little or no
      increased sensitivity to four topoisomerase II inhibitors. Irs3 proved to be
      particularly hypersensitive to DNA crosslinking agents (5-15-fold) such as 1,3
      butadiene diepoxide and mitomycin C. Irs1 was hypersensitive (3-fold or greater)
      to simple alkylating agents, oxidative mutagens and topoisomerase I and II
      inhibitors and exhibited extreme sensitivity (20-100-fold) to DNA crosslinking
      agents. The cellular hypersensitivities of irs2 and irs3 were reflected at the
      level of the chromosome. Camptothecin induced chromosomal aberrations in irs2
      consisted almost exclusively of chromatid deletions and exchanges, whilst in irs3
      1,3 butadiene diepoxide induced a 50-fold increase in chromatid exchanges
      compared with V79-4. The nature of irs2's camptothecin hypersensitivity was
      investigated. Analysis of the protein associated DNA single strand breaks
      produced by camptothecin indicated that there was no difference between V79-4 and
      irs2 in either the number of breaks induced or in the rate of their reversal
      following drug removal. In addition, levels of topoisomerase I activity in V79-4
      and irs2 were indistinguishable. The data presented suggest that irs3 is likely
      to be defective in some aspect of DNA cross-link removal and irs2, whilst showing
      no gross defect in DNA strand break repair may fail to correctly respond to or
      repair certain types of strand breaks, possibly those associated with replicating
      DNA. The phenotypes of irs2 and irs3 respectively show similarities to those of
      cultured cells from the syndromes ataxia telangiectasia and Fanconi's anaemia.

PMID- 8269617
TI  - Elevated 8-hydroxydeoxyguanosine in hepatic DNA of rats following exposure to
      peroxisome proliferators: relationship to carcinogenesis and nuclear
      localization.
AB  - Increased oxidative DNA damage due to increased peroxisomal generation of H2O2 is
      a potential mechanism in the carcinogenicity of chemical peroxisome proliferators
      (PP) in rodent liver. In order to determine the relationship between
      carcinogenicity and peroxisome-dependent DNA damage, levels of DNA base oxidation
      were examined by comparing 8-hydroxydeoxyguanosine (8-OHdG) in DNA from
      unfractionated liver of male F344 rats following dietary exposure to PP [WY
      14,643, 0.1% or 0.005%; di(2-ethylhexyl)phthalate (DEHP), 1.2%; clofibric acid,
      0.5%] or phenobarbital (0.05%). Exposure-related increases in 8-OHdG were not
      observed at 3 or 11 weeks for any of the compounds fed. At 22 weeks, 8-OHdG was
      similarly elevated (2-3x) by WY-14,643 (0.1% and 0.005%) and clofibric acid
      (0.5%). These equivalent increases in 8-OHdG in DNA from unfractionated liver did
      not parallel the divergent carcinogenicity of these different dietary exposures
      in the present or previous studies. The potential oxidation of nuclear DNA was
      examined by comparing levels of 8-OHdG in DNA isolated from purified liver nuclei
      and unfractionated liver. Elevated levels of 8-OHdG were not detected in DNA
      isolated from nuclear fractions of livers from rats fed clofibric acid for 22
      weeks, indicating the dependence of PP-induced oxidative DNA damage on
      extranuclear components of samples for DNA isolation. The absence of a
      quantitative relationship between PP-induced carcinogenicity and oxidative DNA
      base damage (as 8-OHdG), and the failure to localize this oxidative damage to
      nuclear DNA, suggest two possible conclusions: (1) quantitation of 8-OHdG, a
      specific and sensitive indicator of oxidative DNA damage, does not accurately
      reflect the potential peroxisomal H2O2-dependent DNA damage and carcinogenicity
      of PP exposure in rodents; (2) other hepatic responses may be more critical
      features of the mechanism of PP carcinogenicity.

PMID- 8269618
TI  - Reduced autophagic activity in primary rat hepatocellular carcinoma and ascites
      hepatoma cells.
AB  - Autophagy, measured as the sequestration of an endogenous cytosolic enzyme (LDH),
      showed a progressive rate reduction during diethylnitrosamine-induced rat liver
      carcinogenesis. In primary hepatocellular carcinomas the autophagic activity was
      only one-fourth of that seen in normal hepatocytes. Reduced autophagy was also
      observed in peritumorous hepatocytes and in cells from preneoplastic liver, and a
      complete suppression of autophagic protein degradation was seen in normal
      hepatocytes treated with ascitic fluid from an ascites hepatoma, suggesting that
      tumour cells and their precursors may produce autophagy-suppressive factors with
      an autocrine and paracrine action. In cells from the transplantable rat ascites
      hepatoma, Yoshida AH-130, autophagic activity was negligible during active
      (logarithmic) growth, but increased to approximately 0.4%/h at high cell density,
      i.e. in stationary phase. In contrast to normal hepatocytes, autophagy in the AH
      130 cells was not inhibited by ascitic fluid. The hepatoma cells would thus
      appear to have lost some aspects of autophagy regulation while retaining others.
      However, even the highest rate of hepatoma cell autophagy was only one-tenth of
      the maximal activity seen in normal hepatocytes, confirming the hypothesis that
      reduced autophagy may be an important aspect of growth deregulation in liver
      cancer.

PMID- 8269619
TI  - Inhibition of chrysarobin skin tumor promotion in SENCAR mice by antioxidants.
AB  - The present study was designed to further investigate the role of reactive oxygen
      species in the mechanism of action of anthrone tumor promoters. To accomplish
      this, the effects of several antioxidants on the induction of epidermal ornithine
      decarboxylase (ODC) activity, epidermal hyperplasia, skin edema, and skin tumor
      promotion by chrysarobin (1,8-dihydroxy-3-methyl-9-anthrone) were tested.
      Ascorbyl palmitate (AP), given 5 min prior to the promoter at 1 and 4 mumol
      doses, effectively inhibited the induction of ODC activity (28% and 59%,
      respectively) by 220 nmol of chrysarobin. Using a similar protocol, alpha
      tocopherol acetate (alpha-TA) at 10 and 40 mumol doses also effectively inhibited
      the induction of ODC activity (36% and 70%, respectively) by 220 nmol of
      chrysarobin. In contrast, butylated hydroxyanisole (BHA) at doses up to 56 mumol
      per mouse was ineffective at inhibiting the induction of ODC by chrysarobin. AP
      at the 4 mumol dose significantly inhibited the induction of edema by chrysarobin
      by 24% and the induction of epidermal hyperplasia by 23%. alpha-TA at the 40
      mumol dose also significantly inhibited chrysarobin-induced edema by 22% and
      epidermal hyperplasia by 17%. Skin tumor promotion in mice initiated with 25 nmol
      of 7,12-dimethylbenz[a]anthracene and promoted with once-weekly treatments of 220
      nmol chrysarobin was markedly inhibited by treating mice with either AP or alpha
      TA 5 min prior to promoter treatment. AP at 1 and 4 mumol doses significantly
      reduced the number of papillomas per mouse, by 48% and 44%, respectively. alpha
      TA at 10 and 40 mumol doses also significantly reduced the number of papillomas
      per mouse, by 33% and 59%, respectively. In two separate tumor experiments, BHA
      at 2.8 and 5.6 mumol failed to inhibit chrysarobin tumor promotion. The current
      results provide further support for a role of reactive oxygen species in the
      tumor promoting activity of anthrones. In addition, the data indicate that the
      phenolic antioxidant BHA is an ineffective inhibitor of anthrone tumor promotion.

PMID- 8269620
TI  - Diethylnitrosamine administration in vivo increases hepatic poly(ADP-ribose)
      levels in rats: results of a modified technique for poly(ADP-ribose) measurement.
AB  - Poly(ADP-ribose) (polymer) is enzymatically synthesized on nuclear proteins in
      response to DNA strand breaks. NAD+ is the substrate for this reaction, which is
      catalyzed by poly(ADP-ribose)polymerase. This post-translational modification
      occurs in response to DNA strand breaks and is thought to play an important role
      in DNA repair. Polymer synthesis resulting from DNA damage has been described in
      cultured cells, but measurement is more difficult in animal tissues. In this
      study, modifications were made to an earlier method to measure carcinogen-induced
      increases in polymer levels in vivo. RNase I was added to the enzyme mixture used
      to digest polymer to ribosyladenosine (RAdo). This prevented the inhibition of
      snake venom phosphodiesterase by RNA. The HPLC analysis was improved, allowing
      elimination of the second boronate affinity chromatography step traditionally
      used to purify epsilon RAdo. Using this technique, we have studied the effect of
      i.p. diethylnitrosamine (DEN) injection on hepatic NAD+ and poly(ADP-ribose)
      levels in Fischer-344 rats. Hepatic polymer levels rose 8-fold from 26 to 218
      pmol/g liver wet weight, 10 h following 200 mg DEN/kg body weight (n = 4-5).
      Liver NAD+ decreased concurrently, to 61% of basal levels at 16 h post-treatment
      (n = 4-5). Erythrocyte NAD+ concentrations remained unchanged, despite carcinogen
      administration. The DEN-induced effects on tissue polymer and NAD+ levels were
      dose dependent from 0 to 200 mg DEN/kg body weight (n = 4).

PMID- 8269621
TI  - Metabolism of the food-derived mutagen/carcinogen 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP) in nonhuman primates.
AB  - Metabolism of the food-derived heterocyclic amine mutagen/carcinogen 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was examined in cynomolgus monkeys.
      [3H]PhIP (50 mumol/kg, p.o.) was extensively metabolized, with only 1% of the
      dose excreted into the urine as parent compound. Four metabolites were isolated
      by HPLC and identified: PhIP-4'-O-glucuronide, PhIP-4'-sulfate, 4'-hydroxy-PhIP
      and a glucuronide conjugate of N-hydroxy-PhIP. All four metabolites were detected
      in urine, bile and plasma of monkeys. 4'-Hydroxy-PhIP and PhIP were found in
      feces. The major PhIP metabolite in urine, bile and plasma was PhIP-4'-sulfate.
      In urine this metabolite constituted approximately 64-72% of the radioactivity
      excreted. The clearance of PhIP and PhIP metabolites from plasma was rapid, with
      the largest elimination occurring within 8 h. Administration of nine consecutive
      daily doses of unlabeled PhIP (50 mumol/kg, p.o.) prior to administration of
      [3H]PhIP (50 mumol/kg, p.o.) did not alter the plasma clearance of radiolabeled
      PhIP or PhIP metabolites, suggesting that this multiple-dose regimen did not
      induce or alter PhIP metabolism. PhIP formed DNA adducts in white blood cells, as
      determined by the 32P-postlabeling method. The levels of PhIP-DNA adducts in
      blood appeared to peak 3 h after administering a single dose of PhIP (50
      mumol/kg, p.o.) and were still detected 1 week after dosing. The presence of the
      glucuronide conjugate of N-hydroxy-PhIP in urine, bile and plasma, and the
      presence of PhIP-DNA adducts in white blood cells indicate that PhIP undergoes
      metabolic activation via N-hydroxylation in cynomolgus monkeys. The results
      suggest that PhIP is activated in vivo to genotoxic metabolites in nonhuman
      primates and thus is a potential carcinogen in this species.

PMID- 8269622
TI  - Seasonal variation of aromatic DNA adducts in human lymphocytes and granulocytes.
AB  - DNA adducts were measured by 32P-postlabelling in lymphocytes and granulocytes of
      75 healthy men exposed occupationally and environmentally to high concentrations
      of aromatic compounds in the ambient air. Volunteers enrolled in the study were
      men working at the coke batteries and nonoccupationally exposed inhabitants of
      Silesia, a highly industrialized region in southern Poland. Blood samples were
      drawn twice: in February and September 1992. Seasonal variations in the levels of
      DNA adducts were found only in lymphocytes: 3.6- and 8.7-fold in the
      occupationally and environmentally exposed groups respectively. In smokers the
      seasonal variation was as large as 12.8-fold in the environmentally exposed
      group. No seasonal variations were observed in granulocytes. The observed
      seasonal variation in the level of aromatic DNA adducts coincided with
      winter/summer differences in the concentrations of benzo[a]pyrene in the ambient
      air of Silesia. The study recommends the application of lymphocytes for adduct
      studies in chronic exposures and provides evidence on the repair of aromatic
      adducts in lymphocytes.

PMID- 8269623
TI  - The development of hepatocellular carcinoma in initiated rat liver after a brief
      exposure to orotic acid coupled with partial hepatectomy.
AB  - Previous work from this laboratory has revealed that a minimum of 10-20 weeks of
      continuous exposure to 1% dietary orotic acid (OA) is necessary for this regimen
      to exert a significant promoting effect on the carcinogenic process in rat liver.
      The present study investigates the effect of partial hepatectomy (PH), given
      during a short-term exposure (4 weeks) to OA, on the development of hepatocyte
      nodules (HN) and hepatocellular carcinoma (HCC) initiated by diethylnitrosamine
      (DEN). Male Fischer 344 rats (130-150 g) were given a single dose of DEN (200
      mg/kg body wt i.p.). Starting a week later they were fed either a semisynthetic
      basal diet (BD) or the same diet containing 1% OA for 2 weeks; two-thirds PH was
      then performed followed by another 2 weeks of BD or OA diet respectively. At the
      end of this treatment some animals from both groups were killed while the rest
      were continued on BD and killed at 20 or 56 weeks thereafter. The results showed
      no difference between the two groups in the incidence of gamma
      glutamyltransferase-positive foci when rats were killed at 2 weeks after PH.
      However, 4 week exposure to OA coupled with PH significantly enhanced the
      incidence of HN and HCC when this protocol was followed by 20 or 56 weeks of BD
      feeding respectively, leading to 63% incidence of HCC in the OA-fed group, while
      no HCC was observed in control animals. It is concluded that a type of stable or
      permanent change(s) ('imprinting' or 'memory effect') is induced in the initiated
      rat liver by this treatment, which imposes a promoting environment in the liver
      even after withdrawal of the promoter.

PMID- 8269624
TI  - Moderate enhancement of the promotion phase of skin tumorigenesis in hairless
      mice by topical pretreatment with a mitosis-inhibiting epidermal pentapeptide.
AB  - The effect of the physiological epidermal proliferation inhibitory substance
      (EPP) pGlu-Glu-Asp-Ser-GlyOH on the promotion phase in two-stage carcinogenesis
      was investigated. EPP could be the active component in what has been called
      epidermal chalone. Hairless mice were given an initial application of 100 nmol
      7,12-dimethylbenz[a]anthracene in 200 microliters acetone. One week later
      promotion was started with topical applications of 17 nmol 12-O
      tetradecanoylphorbol-13-acetate (TPA) twice a week. Ninety minutes before each
      TPA application the control group received a topical application of 200
      microliters reagent grade acetone and the two experimental groups were given
      either 0.005% or 0.01% EPP in 200 microliters acetone. The mice were observed for
      time of occurrence and time of regression of papillomas. The number of tumors
      produced by the group given the inhibitory substances before TPA increased, and
      so did the percentage of tumor-bearing animals. There was also a tendency towards
      a higher degree of papilloma regression in the animals treated with EPP before
      TPA. We have previously shown that EPP enhances methylnitrosourea (MNU)
      carcinogenesis. Since we regard TPA as a skin-irritating promoter with weak
      carcinogenic potency, very different from MNU, the fact that EPP has the same
      enhancing effect on promotion as it has on complete MNU carcinogenesis raises
      some very interesting questions, and may indicate a similarity between the
      mechanisms in promotion and complete carcinogenesis. Some possible explanations
      of the results are discussed, e.g. whether the transit zone late G1/S of the cell
      cycle is the most sensitive one for carcinogenic or tumorigenic effects.

PMID- 8269625
TI  - N-nitroso compounds in fresh gastric juice and their relation to intragastric pH
      and nitrite employing an improved analytical method.
AB  - In order to examine further the relationship between intragastric N-nitrosation,
      gastric pH and nitrite, 457 fresh, fasting gastric juice samples were analysed
      for total N-nitroso compounds (NOC) and nitrite concentrations using a recently
      described improved assay method. Nitrite in log values was linearly related to
      intragastric pH (r = 0.887, P < 0.01) with a regression equation log[nitrite]
      (mumol/l) = 0.489 x pH - 2.209. Significantly higher NOC concentrations were
      found at intragastric pH ranges of 1.13-2.99 (mean +/- SE: 1.45 +/- 0.17 mumol/l,
      P < 0.05) and 6.00-8.42 (3.57 +/- 0.33 mumol/l, P < 0.01) compared with that at
      pH 3.00-5.99 (1.02 +/- 0.12 mumol/l). NOC concentration was significantly related
      to log nitrite concentration at both the low pH range 1.13-4.99 (r = 0.169, P <
      0.01) and the high pH range 5.00-8.42 (r = 0.450, P < 0.01). The results in the
      present study confirm that both acid-catalysed N-nitrosation and biologically
      catalysed N-nitrosation occur in the human stomach. However, great variations in
      nitrite and NOC concentrations were observed in both low and high pH samples,
      indicating that, as expected, both the acid-catalysed N-nitrosation and
      biologically-catalysed N-nitrosation processes are markedly affected by factors
      other than intragastric pH and nitrite.

PMID- 8269626
TI  - Dose-dependence of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP)
      carcinogenicity in rats.
AB  - The dose-dependence of 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP)
      carcinogenicity was investigated in F344 rats of both sexes administered the
      heterocyclic amine in the diet at concentrations of 25 or 100 p.p.m. for up to
      104 weeks. Incidences of mammary adenocarcinomas were 7% (2/30) for 25 p.p.m. and
      47% (14 of 30 rats) for 100 p.p.m. in females and those of colon adenocarcinomas
      were 43% (13/30) for males and 13% (4/30) for females of the 100 p.p.m. groups.
      No mammary adenocarcinomas were induced in males and no colon carcinomas were
      observed in the 25 p.p.m. groups of either sex. Furthermore, development of
      lymphocytic leukemia was apparently enhanced by PhIP in males. In a separate
      experiment, dose-dependent induction of aberrant crypts in the large intestine,
      considered as preneoplastic lesions, was evident after 8 weeks feeding of PhIP
      supplemented diet at doses of 25, 100 or 400 p.p.m. Thus a clear dose-dependency
      was demonstrated for both colon and mammary carcinogenesis. Since PhIP is a
      particularly abundant heterocyclic amine and its carcinogenic organotropism
      overlaps with the types of neoplasias most commonly observed in western
      countries, the compound may be extremely important with respect to human cancer
      development.

PMID- 8269627
TI  - The effect of the chemotherapeutic drug VP-16 on poly(ADP-ribosylation) in
      apoptotic HeLa cells.
AB  - We have studied the effect of the chemotherapeutic drug VP-16 (etoposide) on the
      metabolism of HeLa cells by analysing different cellular parameters; in
      particular we have focused on changes in cellular morphology that are considered
      as markers of apoptosis. By immunofluorescence experiments we have shown that VP
      16 causes the complete disruption of nucleoli and induces chromatin margination
      and fragmentation. Agarose gel electrophoresis of DNA from cells treated with 10
      100 microM VP-16 showed the appearance of a characteristic ladder due to the
      internucleosomal DNA cleavage. The effect of etoposide on DNA integrity was not
      prevented by preincubation of cells with the protein synthesis inhibitor
      cycloheximide. These results provide experimental evidence indicating that the
      typical features of apoptosis are visible in HeLa cells exposed to VP-16. In this
      experimental system we have investigated whether the ADP-ribosylation process
      could be regulated by the presence of DNA fragments. By means of the activity gel
      technique, which allows the direct evaluation of automodified poly(ADP
      ribose)polymerase, we have observed that in extracts from cells where etoposide
      induced DNA fragmentation occurred, the autoribosylated form of the enzyme is
      greatly increased. Ribosylated poly(ADP-ribose)polymerase has been isolated by
      affinity chromatography on boronate column from cells permeabilized and labelled
      with [32P]NAD. Drug exposure caused a strong augmentation of modified enzyme.
      These observations suggest that activation of ADP-ribosylation process occurs in
      cells that show the typical features of apoptosis.

PMID- 8269628
TI  - The intensity of vanadium(V)-induced cytotoxicity and morphological
      transformation in BALB/3T3 cells is dependent on glutathione-mediated
      bioreduction to vanadium(IV).
AB  - Cytotoxicity and morphological transformation has been studied in BALB/3T3 Cl A31
      1-1 mouse embryo cells for ammonium vanadate [vanadium(V)] and vanadyl sulphate
      [vanadium(IV)] alone or in combination with diethylmaleate (DEM), a cellular
      glutathione (GSH)-depleting agent. Cells exposed for 24 h to 10(-5) M vanadium(V)
      alone or in combination with 3 x 10(-6) M DEM showed the characteristic hyperfine
      EPR signal of vanadium(IV), which was more obvious in the case of exposure to
      vanadium(V) alone. This suggests that the amount of vanadium(V) reduced to
      vanadium(IV) decreased in GSH-depleted cells. While vanadium(IV) at
      concentrations of 3 x 10(-6) M and 10(-5) M was not transforming in the cells,
      vanadium(V) showed neoplastic transforming activity (P < 0.025 and P < 0.001 for
      the two doses, respectively) in comparison to controls (vanadium unexposed
      cells). Cytotoxicity and morphological transformation in cells exposed to
      vanadium(V) in combination with 3 x 10(-6) M DEM were significantly more
      intensive (P < 0.005 and P < 0.01 for the two doses of vanadate tested) compared
      to the corresponding values observed in cells exposed to vanadium(V) alone. This
      suggests that the final transforming activity response is dependent on the
      intracellular GSH-mediated mechanism of reduction of vanadium(V) to vanadium(IV):
      (i) the extent to which vanadium(V) should be bioreduced to less toxic
      vanadium(IV) via intracellular GSH is a key point in determining the intensity of
      the observed neoplastic action; (ii) the carcinogenic potential of vanadium(V)
      should be strictly dependent on its intracellular persistence which could lead to
      changes in normal metabolic patterns of vanadium(V) in the oxidized form due to
      lack of GSH-mediated reduction.

PMID- 8269629
TI  - Enhanced expression of annexin II in human pancreatic carcinoma cells and primary
      pancreatic cancers.
AB  - Annexin II is a calcium and phospholipid binding protein and a substrate for
      protein-tyrosine kinases. Recent investigations have revealed involvement of
      annexin II in DNA synthesis and cell proliferation. Increased levels of annexin
      II are observed in cancer cells and tissues. To investigate the expression of
      annexin II in pancreatic adenocarcinoma cells and primary tumors, we measured the
      levels of annexin II mRNA and protein in normal human pancreas, five established
      human pancreatic adenocarcinoma cell lines, three primary pancreatic cancers and
      one metastatic tumor. All five cell lines examined had 5- to 15-fold higher
      levels of annexin II as compared to normal pancreas. Significant elevations (2-
      to 8-fold) of annexin II expression were observed in the three primary pancreatic
      tumors and one metastatic tumor examined. Immunocytochemical analysis indicates
      that the increased expression of annexin II is limited to proliferating ductular
      adenocarcinoma, and annexin II expression co-localizes with cells that express
      PCNA. In normal pancreas, annexin II expression is seen in ductal and ductular
      cells and no expression is seen in acinar or islet cells. We conclude from these
      findings that annexin II has a role in cell proliferation and its regulation is
      altered in pancreatic cancer.

PMID- 8269630
TI  - Tissue protein turnover during liver carcinogenesis.
AB  - Overall rates of tissue protein degradation in vivo during chemical
      hepatocarcinogenesis were estimated by a double-isotope method as well as from
      the accumulation of peptide intermediates in protein degradation induced by
      bestatin. Several parameters estimating rates of cell proliferation and cell loss
      have been measured in parallel. The two procedures adopted consistently indicated
      that protein turnover was significantly slowed down through the whole observation
      period (12 months after the initiating administration of DENA) in both
      'preneoplastic' nodules and hepatomas as compared with control livers or
      perinodular tissue. Such a difference may confer a selective growth advantage to
      'preneoplastic' and tumoral cells. Since protein degradation rates did not
      appreciably differ between nodules and hepatomas, either such advantage
      originated from some early step in the carcinogenetic process or it merely
      reflected the proliferative events in the two cell populations. Yet neither liver
      nodules nor hepatomas were characterized by very high rates of cell
      proliferation, however much increased with respect to control liver.

PMID- 8269631
TI  - Comparison of p53 protein expression and cellular localization in human and
      hamster pancreatic cancer cell lines.
AB  - We compared the expression of p53 protein in four human pancreatic cancer cell
      lines (HPAF, CD11, CD18 and PANC-1) and four hamster pancreatic cancer cell lines
      (PC-1, PC-1.2, PC-1.0 and H2T) by the monoclonal antibodies PAb421 and PAb240.
      PAb421 reacted with all human pancreatic cancer cell lines but not with the
      hamster cells. PAb240, on the other hand, reacted with all human and hamster
      pancreatic cancer cell lines in immunoblotting and in immunocytochemistry.
      However, immunoprecipitation with PAb240 was detected only in human cell lines
      HPAF, CD11 and CD18 cells but not in PANC-1 or in any of the hamster cell lines.
      During exponential growth, immunoreactivity was detected mainly in the nucleus of
      PC-1, PC-1.2 and PANC-1 cells (nuclear type) and in both the nucleus and the
      cytoplasm of PC-1.0, H2T, HPAF, CD11 and CD18 cells (diffuse type). At the
      confluence, the expression of p53 was decreased in most of the human cell lines
      as was proliferative cell nuclear antigen. After incubation with 1 mM
      hydroxyurea, cells with nuclear p53 expression did not show an altered cellular
      distribution of p53 protein, whereas cells with a diffuse type of localization
      pattern showed an increase in the nuclear staining. On the other hand,
      cytoplasmic immunoreactivity was found in PC-1.0, PC-1, PC-1.2, HPAF, CD11 and
      CD18 cells that were treated with 100 ng/ml of nocodazole. After heat stress with
      1 h incubation at 42 degrees C, p53 protein was detected in the cytoplasm and
      nucleolus of all cell lines. After 24-48 h incubation at 37 degrees C, this
      change in cellular distribution of p53 in response to heat stress was reverted to
      a preheat stress pattern. The overall results suggest that neither the p53 of
      PANC-1 nor the hamster pancreatic cancer cell lines are immunoprecipitated with
      the PAb240. It appears that cell cycle and heat stress are two of the factors
      that influence cellular localization of p53 protein in both human and hamster
      pancreatic cancer cells.

PMID- 8269632
TI  - Para-aminobenzoic acid suppression of cis-diamminedichloroplatinum(II)
      nephrotoxicity.
AB  - Concurrent administration of para-aminobenzoic acid (PABA) reduced the toxicity
      of cis-diamminedichloroplatinum(II) (DDP) in a dose-related manner in rats. When
      administered i.p. simultaneously with 7.5 mg/kg DDP, PABA (100 mg/kg)
      significantly reduced plasma urea nitrogen (PUN) and plasma creatinine levels as
      well as DDP-induced weight loss. Increasing doses of PABA (25, 50 and 100 mg/kg)
      correlated with progressively better parameters of renal activity and body wt and
      with lower levels of platinum in plasma and tissues in rats killed 5 days after
      drug administration. The formation of cisplatin-DNA adducts, the total platinum
      levels in kidney and testes and the DDP-induced tumor response were investigated
      in the presence and absence of PABA exposure in mice bearing P388 leukemic cells.
      Renal and testicular DNA-adducts in mice treated i.p. with 16 mg/kg DDP in normal
      saline were higher than those observed in mice receiving the same protocol and
      added PABA. Analysis of tissue platinum content demonstrated significantly lower
      platinum levels both in kidneys (P < 0.05) and testes (P < 0.01) of mice
      receiving DDP and PABA in normal saline compared to those receiving only DDP in
      normal saline. PABA did not affect the in vivo and in vitro antitumor activity of
      DDP against P388 leukemia, and there was no significant PABA-induced modification
      in the concentration of platinum both in the tumor cells and in DNA samples
      isolated from P388 leukemic cells of DDP-treated mice. We conclude that PABA may
      be a promising compound for reducing DDP-toxic side effects, including
      nephrotoxicity, without compromising its antitumor activity.

PMID- 8269633
TI  - N-acetylbenzidine-N'-glucuronidation by human, dog and rat liver.
AB  - While N-glucuronidation is an important pathway for metabolism of aromatic
      amines, it has not been demonstrated for N-acetylbenzidine. A glucuronide of N
      acetylbenzidine was synthesized and identified by mass spectrometry as N
      acetylbenzidine-N'-glucuronide. This N'-glucuronide is acid labile with a t1/2 of
      4 min at pH 5.3. A similar acid lability was also observed with benzidine-N
      glucuronide. The formation of N-acetylbenzidine-N'-glucuronide was assessed with
      liver slices and microsomes prepared from human, dog and rat. When 0.014 mM [3H]N
      acetylbenzidine was incubated with human liver slices a significant amount of N
      acetylbendizine-N'-glucuronide was produced (8-26% of the total radioactivity
      recovered). With higher concentrations of [3H]N-acetylbenzidine (1 mM) rat slices
      also produced N-acetylbenzidine-N'-glucuronide. However, N'-glucuronide formation
      was not detected with dog liver slices incubated with either 0.014 or 1 mM [3H]N
      acetylbenzidine. N-Acetylbenzidine-N'-glucuronide formation was observed with
      microsomes prepared from human, dog and rat. To assess maximum activity four
      detergents were used at two concentrations. With or without detergent activation
      the relative amount of glucuronidation was human > > dog > rat. The rate of
      benzidine N-glucuronide formation was 4.3- and 1.6-fold greater than N
      acetylbenzidine-N'-glucuronide in dog and rat respectively, while in human both
      rates were similar (1.1-fold). With or without detergent activation the relative
      amount of benzidine-N-glucuronide formation was human > dog > > rat. N
      Glucuronidation of [3H]N,N'-diacetylbenzidine was not observed. Thus N
      actylbenzidine-N'-glucuronide formation appears to be an important pathway for
      metabolism of N-acetylbenzidine, especially in humans. Due to their acid
      lability, formation of the N-glucuronides of N-acetylbenzidine and benzidine
      provides a mechanism for hepatic detoxification and accumulation of these
      carcinogens in the bladder. A new model is described illustrating the effect of N
      glucuronidation and the influence of N-acetylation on arylmono- and aryldiamine
      induced bladder carcinogenesis.

PMID- 8269634
TI  - In vitro metabolism of aflatoxin B1 by normal and tumorous liver tissue from
      Thailand.
AB  - Liver tissues were obtained from 20 liver cancer patients from Thailand, an area
      where the incidence of this tumour is high and where exposure to aflatoxin
      occurs. The expression of hepatic cytochrome P450s (P450) and glutathione S
      transferase (GST) was examined and this expression was compared to the in vitro
      metabolism of aflatoxin B1 (AFB1). There was a > 10-fold inter-individual
      variation in expression of the various P450s including CYP3A4 (57-fold), CYP2B6
      (56-fold) and CYP2A6 (120-fold). Microsomal metabolism of AFB1 to AFB1 8,9
      epoxide (as measured by AFB1 tris-diol formation) and aflatoxin Q1 (AFQ1), the
      major metabolite produced, was significantly correlated with CYP3A3/4 expression
      (P < 0.001) and, to a lesser extent, with CYP2B6 expression (P < 0.01). There was
      a significantly reduced expression of major P450 proteins in microsomes from
      liver tumours compared to microsomes from the paired normal liver when analysed
      by Western immunoblot analysis. The production of AFQ1 and AFB1 tris-diol was
      almost uniformly reduced in tumours, but interestingly, the production of AFP1
      was significantly increased. The immunoreactive expression of the major human
      classes of cytosolic GSTs (alpha, mu and pi) was also analyzed in normal and
      tumorous liver tissue. The expression of GSTA (alpha) and GSTM (mu) class
      proteins was markedly decreased and GSTP (pi) increased in the majority of tumour
      cytosols compared to normal liver. The cytosolic GST activity (1-chloro-2,4
      dinitrobenzene conjugation) was significantly lower in liver tumours compared to
      normal liver (193 +/- 149 versus 875 +/- 299 nmol/min/mg, P < 0.0001), as was
      glutathione peroxidase (GPx) activity (cumene hydroperoxide) (26 +/- 23 versus 70
      +/- 26 nmol/min/mg respectively, P < 0.005). Ten out of 14 individuals (71%) were
      homozygous null when genotyped for GSTM1. There was no detectable conjugation of
      AFB1 8,9-epoxide to glutathione by cytosol either from tumorous or normal liver.
      Thus, capacity of human cytosols to conjugate reactive AFB1 metabolites to GSH
      resembled AFB1-sensitive species such as rat, trout and duck rather than
      resistant species such as mouse and hamster. These data indicate a strong
      capacity of multiple forms of human hepatic P450s to metabolize AFB1 to both the
      reactive intermediate AFB1 8,9-epoxide and the detoxification product AFQ1. These
      results suggest that in view of the lack of significant GST-mediated protection
      against AFB1 in human liver, variations in expression of hepatic P450, due either
      to genetic polymorphisms or to modulation by environmental factors, may be
      important determinants in the risk of liver cancer development in AFB1-exposed
      populations.

PMID- 8269635
TI  - Aphidicolin and 1-beta-D-arabinofuranosylcytosine strongly inhibit
      transcriptionally active DNA repair in normal human fibroblasts.
AB  - Both aphidicolin and 1-beta-D-arabinofuranosylcytosine (araC) inactivate DNA
      polymerases alpha, delta and epsilon, and according block long-patch excision
      repair in mammalian cells. We report here that in normal human fibroblasts both
      compounds strongly inhibit the repair of damage induced by UV or 4-nitroquinoline
      1-oxide in the transcriptionally active c-myc gene, as indicated by the
      appearance of DNA strand breaks in carcinogen-treated cultures that were
      subsequently incubated in the presence of either polymerase inhibitor. We further
      demonstrate that the repair of UV photoproducts in the c-myc gene can be
      monitored by photolysis (313 nm) of DNA repaired in the presence of
      bromodeoxyuridine (BrdUrd). In UV-irradiated cultures, the incidence of
      aphidicolin- or araC-accumulated strand breaks was approximately 70% of that
      detected by the BrdUrd photolysis assay. Our data therefore implicate a critical
      role for DNA polymerases alpha, delta and/or epsilon in gene-specific repair in
      human cells. The techniques described here may prove useful in the study of DNA
      repair in defined sequences of the human genome following exposure to a diverse
      array of physical and chemical genotoxic agents.

PMID- 8269636
TI  - Preneoplastic lesions and DNA adduct formation of the airborne genotoxic agents 2
      nitrofluorene and 2,7-dinitrofluorene.
AB  - The urinary mutagenicity (unconjugated forms) after administration of 2,7
      dinitrofluorene (2,7-dNF) orally or i.p. was lower compared to 2-nitrofluorene
      (NF) administration. When partial hepatectomy (PH) was performed before i.p.
      administration, both substances had higher excretion of mutagens in which 2,7-dNF
      increased dramatically and showed a higher level of mutagenicity compared to NF.
      NF and 2,7-dNF formed DNA adducts in liver tissue. By different routes of
      administration (oral or i.p.) of the same substance at the same dose (200 mg/kg
      body wt), the patterns of DNA adducts were different. It seemed to be that PH,
      which was performed 18 h before i.p. administration, had no significant effects
      on the amount of DNA adducts. Generally, the total amount of DNA adducts after
      oral administration was higher compared to i.p. administration. Dramatic
      increases of the nitroreduced DNA adducts were noticed after oral compared to
      i.p. administration. When given i.p., both substances showed initiating capacity
      in foci formation both at 50 mg/kg body wt and 200 mg/kg body wt. When NF and 2,7
      dNF were administered orally by single gavage, 2,7-dNF was more potent as an
      initiator in foci formation compared to NF and the initiating capacity of the two
      substances was higher compared to i.p. administration. The great difference
      between these two nitro-PAHs seen in the bacterial tests for mutagenicity was not
      seen in the in vivo genotoxic experiments. The results indicate that both NF and
      2,7-dNF formed DNA adducts and preneoplastic lesions after both i.p. and oral
      administration. After oral administration, both substances were more potent in
      causing DNA adduct and foci formation compared to i.p. administration. 2,7-dNF
      was more potent as an initiator than NF especially after oral administration. The
      urinary excretion of unconjugated mutagens did not indicate the genotoxic effects
      of the parent substance.

PMID- 8269637
TI  - Intestinal bacteria and endogenous production of malonaldehyde and alkylators in
      mice.
AB  - Association of intestinal bacteria with endogenous production of some reactive
      compounds was studied by determination of adducts to haemoglobin in blood from
      germ-free and corresponding control mice. N-terminal valines in haemoglobin were
      analysed with regard to adducts from malonaldehyde (MA), ethene/ethylene oxide,
      propene/propylene oxide and methylating agents. It was found that the adduct
      levels from MA were 1.65 and 3.32 nmol/g globin in germ-free and control mice,
      respectively. The levels of adducts from ethylene oxide and propylene oxide were
      10.8 and 10.3 pmol/g globin, respectively, in germ-free and 21.7 and 17.7 pmol/g
      globin, respectively, in control mice. The level of adducts from endogenous
      methylating agents was higher in germ-free mice than in controls (473 and 408
      pmol/g globin, respectively). These differences in adduct levels between germ
      free and conventional mice are statistically significant. The causes of the
      observed variations are so far not identified. This study confirms earlier
      findings on background levels of adducts in unexposed individuals and supports
      the hypothesis that these adducts reflect the occurrence of reactive
      intermediates in vivo that may constitute cancer risks in background cancer
      incidence. The present study also shows that intestinal bacteria may be an
      important determinant of such endogenous risk factors.

PMID- 8269638
TI  - The glucuronidation of hydroxylated metabolites of benzo[a]pyrene and 2
      acetylaminofluorene by cDNA-expressed human UDP-glucuronosyltransferases.
AB  - The capacity of four cDNA-expressed human liver UDP-glucuronosyltransferases
      (UGT), UGT1*6, UGT2B7, UGT2B10 and UGT2B11, to glucuronidate hydroxylated
      metabolites of benzo[a]pyrene (B[a]P) and 2-acetylaminofluorene (AAF) has been
      investigated. UGT1*6 and UGT2B7 glucuronidated a range of B[a]P and AAF
      metabolites with a degree of regiospecificity, although UGTs 2B10 and 2B11 were
      inactive towards all compounds screened. UGT2B7 glucuronidated the B[a]P trans
      4,5- and 7,8-dihydrodiols and the 1-,2-,4-,5-,6-,8-,9- and 10-monophenols. In
      contrast, UGT1*6 lacked activity towards the dihydrodiols and metabolized a more
      limited range of monophenols, namely 4-,5-,8- and 12-hydroxyB[a]P. Both UGT2B7
      and UGT1*6 glucuronidated N, 1-,3- and 8-hydroxyAAF, but 5-hydroxyAAF was
      metabolised only by UGT1*6. Neither enzyme glucuronidated 3-,7- and 11
      hydroxyB[a]P and 7- and 9-hydroxyAAF, although these compounds were all
      metabolised by human liver microsomal UGTs. The results suggest that the relative
      content of UGT isoforms in a cell or tissue will be important for determining the
      extent to which a particular carcinogen/mutagen is deactivated.

PMID- 8269639
TI  - Inhibition of both stage I and stage II skin tumor promotion in SENCAR mice by a
      polyphenolic fraction isolated from green tea: inhibition depends on the duration
      of polyphenol treatment.
AB  - The polyphenolic fraction isolated from green tea (GTP) is a potent inhibitor of
      phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotion
      in mouse skin. In this study, we assessed the effect of GTP on both stage I and
      stage II skin tumor promotion, and also analyzed the effect of duration of GTP
      treatment on skin tumor promotion in SENCAR mice. Topical application of GTP (6
      mg/animal) concurrently with each application of either TPA (3.2 nmol) or
      mezerein (3.2 nmol) in stage I or stage II of the murine skin tumor promotion
      protocol, respectively, resulted in significant protection against skin papilloma
      formation in terms of both tumor multiplicity (42-50%) and tumor growth (43-54%).
      More profound and sustained protective effects of GTP were evident when it was
      applied continuously during both stage I and stage II of the skin tumor promotion
      protocol concurrently with TPA or mezerein treatments, respectively. Under this
      treatment regimen, compared to non-GTP-treated positive controls, GTP application
      showed 71%, 37% and 74% protection in terms of tumor multiplicity, tumor
      incidence and tumor growth, respectively. These data indicate that GTP inhibits
      both stage I and stage II of skin tumor promotion and that the inhibition of
      tumor promotion depends on the duration of GTP treatment.

PMID- 8269641
TI  - Evaluation of c-K-ras in pancreatic carcinomas from Ela-1, SV40E transgenic mice.
AB  - c-K-ras is activated by mutation at codon 12 in the majority of human pancreatic
      carcinomas of ductal, but not acinar, phenotype. Therefore, evaluation of c-K-ras
      in experimentally induced pancreatic carcinomas in animal models is of interest
      for comparison with the human disease. Acinar cell carcinomas and islet cell
      tumors arising in two strains of transgenic mice carrying the Ela-1-SV40E
      transgene were evaluated using the polymerase chain reaction and allele specific
      oligomer hybridization to seek evidence of c-K-ras mutation at codons 12, 13 and
      61. Amplified DNA products, including codons 12 and 13, from the majority of
      these tumors were also evaluated by single strand conformation polymorphism
      analysis. Only wild type c-K-ras was found in the tumors.

PMID- 8269640
TI  - Diacylglycerol is an effector of the clonal expansion of cells containing
      activated Ha-ras genes.
AB  - Diacylglycerols (DAG) are lipid second messengers which are generated during
      phospholipase-catalyzed hydrolysis of phospholipids. The model DAG, sn-1,2
      didecanoylglycerol (DIC10), is an effective topical tumor promoter in 7,12
      dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. We now report that 11/12
      of DMBA-initiated/DIC10-promoted papillomas examined contain an A-->T mutation in
      the 61st codon of the Ha-ras gene, suggesting that DAGs affect the clonal
      expansion of activated Ha-ras-containing cells. To explore further the DIC10
      induced clonal expansion of activated Ha-ras-containing cells, we have examined
      the tumor-promoting effect of DIC10 in the skin of transgenic TG.AC mice, which
      harbor a v-Ha-ras transgene. By 9 weeks of promotion, 100% of the TG.AC mice
      developed squamous papillomas and by 15 weeks these mice developed > 20
      papillomas/mouse. Because fatty acids are known to participate in signal
      transduction pathways, and since cellular lipases could cleave the fatty acid
      side chains present in DIC10, we have examined the tumor promoting activity of n
      decanoic acid to verify the specificity of promotional activity of DIC10. n
      Decanoic acid did not function as a tumor promoter. These data implicate DAG as
      an effector of the clonal expansion of mutated Ha-ras-containing cells, and
      support a mechanism whereby an increase in endogenous DAG could contribute to the
      clonal expansion of cells containing a Ha-ras oncogene.

PMID- 8269642
TI  - Alteration in regional brain catecholamines during and after acute hemorrhage in
      the rat.
AB  - Using high-performance liquid chromatography (HPLC), we carried out a
      simultaneous assay of norepinephrine (NE), epinephrine (E), and dopamine (DA) in
      specific brain regions before and at 5 min, 30 min, 1 hr, 2 hr, and 24 hr
      following acute hemorrhage in the rat. Thirty-six awake male Sprague-Dawley rats
      were subjected to rapid fixed-volume hemorrhage (8.5 ml/300 g) over 5 min. In the
      hypothalamus, concentrations of NE and E fell markedly and significantly by 5 min
      posthemorrhage (P < 0.001), while hypothalamic DA concentrations fell gradually
      to reach a nadir by 2 hr (P < 0.005). Hypothalamic concentrations of all three
      catecholamines remained significantly reduced up to 24 hr posthemorrhage.
      Dopamine concentrations in the medulla increased transiently, while striatal DA
      concentrations fell following hemorrhage to reach a nadir by 2 hr (P < 0.001). By
      2 hr posthemorrhage, NE concentrations in both cortex and medulla were
      significantly decreased (P < 0.01 and P < 0.005, respectively), with cortical NE
      levels remaining significantly depressed for up to 24 hr. These results suggest
      that regional and prolonged changes occur in central catecholaminergic systems
      following acute, uncompensated hemorrhage. It is possible that these changes in
      the central nervous system contribute to the cardiovascular dysfunction observed
      following hemorrhage.

PMID- 8269643
TI  - Infusion of stroma-free cross-linked hemoglobin during acute gram-negative
      bacteremia.
AB  - Twelve dogs were divided into two groups of six each, and were infused with bis
      3,5-dibromosalicyl fumarate stroma-free hemoglobin (DBBF-Hb) or albumin. Their
      responses to an intravenous bolus of Escherichia coli were followed for 4 hr.
      Bacterial clearance from the blood stream was studied using standard colony
      counting methodology as well as blood counts, blood chemistries, and clotting
      factor analysis. There was a significant difference in mean arterial pressure
      (MAP) over time between DBBF-Hb-treated dogs and those treated with albumin (P <
      0.02). While the DBBF-treated dogs had a higher MAP during the 10 min of
      bacteremia, after 1 hr, there were no longer any appreciable differences between
      septic dogs treated with DBBF-Hb vs. albumin. Consumption of clotting and natural
      anticoagulant factors was observed to be similar in both groups, as were
      endotoxin levels. Blood urea nitrogen (BUN) increased slightly in both groups,
      while white blood cell counts and clotting factor levels fell in both groups in a
      similar fashion. There was a more pronounced fall (P < 0.04) in platelet counts
      in the animals treated with DBBF-Hb. In the dogs treated with DBBF-Hb, there was
      also a late rise in pCO2 (P < 0.01), a more pronounced fall in pO2, and greater
      acidosis, which suggested that ventilation perfusion abnormalities may have been
      exacerbated by DBBF-Hb treatment. Since the exacerbation of respiratory
      abnormalities was not related to diminished bacterial or endotoxin clearance, the
      possibility is raised that DBBF-Hb interferes with compensatory respiratory
      changes during sepsis.

PMID- 8269644
TI  - Use of fluorescent latex microspheres to measure coronary blood flow
      distribution.
AB  - Radioactive microspheres have long been in use to measure blood flow distribution
      to various vascular beds. Their drawbacks are the short half-lives of the
      radioactive material, the need for appropriate care in handling and disposing of
      such material, and their relative expensiveness. We investigated the use of
      fluorescent microspheres as indicators of coronary blood flow distribution in a
      canine model. Radioactive (125I) microspheres were used as a comparison standard.
      Four colors of fluorescent microspheres were used: blue, yellow-green, orange,
      and red, having emission frequencies ranging from 385 to 605 nM. The experiments
      were carried out in dogs under pentobarbital anesthesia, in which the
      microspheres were given during pump perfusion of the left circumflex artery with
      the animal's own blood. The hearts were removed, fixed for 3 days in 10%
      formalin, and sectioned. Samples from the endocardial, myocardial, and epicardial
      layers were read on a gamma counter. The fluorescent microspheres were extracted
      from the same tissues into ethyl acetate, and read in a fluorescence
      spectrophotometer at the appropriate excitation/emission frequencies. Comparable
      results were obtained from the two methods, with good sensitivity and resolution
      of dye colors, using the fluorescent microspheres.

PMID- 8269645
TI  - Natural adrenocorticosteroids do not restore resistance to endotoxin in the
      adrenalectomized mouse.
AB  - Chronic loss of adrenocorticosteroid activity by adrenalectomy (10 days) or acute
      inhibition of glucocorticoid receptor function by injection of an anti-progestin
      (RU-38486) increased sensitivity to lipopolysaccharide about 200-fold, compared
      to that of control animals. Daily subcutaneous injection of a mixture of the
      natural glucocorticoid corticosterone and the mineralocorticoid
      deoxycorticosterone did not restore resistance to the endotoxin. The largest dose
      of steroid, 400 micrograms corticosterone + 200 micrograms deoxycorticosterone,
      provided only partial protection against 20 micrograms LPS, which was 10% of the
      LD50 for animals with adrenals. The mechanisms involved in lack of effectiveness
      of natural corticosteroids will require further experimentation.

PMID- 8269646
TI  - Liver hemodynamics during portal venous endotoxemia in swine.
AB  - The acute hemodynamic response of the liver to portal endotoxemia was measured in
      six isoflurane anesthetized pigs in which volume support was used to maintain
      normal cardiac output. After baseline monitoring, bacterial endotoxin (LPS) was
      infused over 1 hr into a mesenteric vein at a rate of 1 microgram.kg-1.hr-1, and
      monitoring was continued for 1 hr postinfusion. Peak vasoconstriction occurred
      during LPS infusion in both the hepatic artery (resistance increases 349% of
      baseline, P < 0.05) and the liver's portal circulation (resistance increases 159%
      of baseline, P < 0.05). Increased vascular resistance was also detected in lung
      (increases 433% of baseline) and intestine (increases 130% of baseline) at the
      midpoint of the LPS infusion. The non-splanchnic circulation, defined for our
      analysis as all of the peripheral circulation except the portal and hepatic
      arterial circulation, generally exhibited little change in vascular resistance
      during LPS infusion. LPS was incompletely cleared by the liver, but secondary
      clearance by the lung prevented large increases in the LPS concentration of
      arterial blood. During the first hour postinfusion, the systemic vascular
      resistance subsequently decreased to near normal in all vascular beds, with the
      exception of the liver's portal circulation. A sustained and secondary increase
      in vascular resistance of the liver's portal circulation and portal vein pressure
      occurred during the first hour after LPS infusion. We conclude that most of the
      vasoconstriction in the acute response to portal endotoxemia occurs in the liver
      and lung, organs directly exposed to elevated levels of endotoxins.

PMID- 8269647
TI  - Recombinant amino terminal fragment of bactericidal/permeability-increasing
      protein prevents hemodynamic responses to endotoxin.
AB  - We sought to determine if a recombinant amino terminal fragment of
      bactericidal/permeability increasing protein (rBPI23) alters the hemodynamic
      responses to endotoxin. Experiments were performed on Sprague Dawley rats
      anesthetized with Ketamine and xylazine. In rats challenged with a 30 min
      infusion of 0.25 mg/kg lipopolysaccharide (LPS; Escherichia coli 0111:B4), there
      were early (30-90 min), significant increases in cardiac index, heart rate, and
      stroke volume, accompanied by significant decreases in blood pressure and total
      peripheral resistance. For the remainder of the 210 min observation period,
      cardiac index, and stroke volume progressively declined to levels significantly
      below those of control rats receiving only vehicles. At the same time, blood
      pressure and total peripheral resistance steadily increased above the vehicle
      control group. Infusion of 3 mg/kg of rBPI23 abolished these LPS-induced
      hemodynamic responses. A dose of 1.0 mg/kg of rBPI23 was associated with a
      modest, significant inhibition of changes evoked by LPS, whereas 0.3 mg/kg was
      without significant effect. Thaumatin, a control cationic protein with molecular
      weight and isoelectric point similar to those of rBPI23, failed to alter any
      responses to LPS. These results indicate that rBPI23 produces a dose-dependent
      inhibition of hemodynamic changes, associated with endotoxemia, and provides
      further support for the potential utility of rBPI23 as a therapeutic agent in the
      treatment of gram-negative sepsis and infection.

PMID- 8269648
TI  - Transmigration routes and a delayed systemic hypotension in rats after
      intraperitoneal injection of endotoxin from Escherichia coli.
AB  - An intraperitoneal injection of endotoxin (ETX; 3 mg/kg) to rats caused gradual
      decrease in the systemic arterial blood pressure for up to 3 hr, together with
      decrease in heart rate, increase in hematocrit, and changes in the core
      temperature (an initial increase and a subsequent decrease). Pretreatment of rats
      with indomethacin (10 mg/kg, p.o.) prevented the decrease in the systemic blood
      pressure and the changes in other three parameters. The intraperitoneal injection
      of ETX also induced a gradual increase in exudation of plasma for up to 3 hr,
      with increased levels of prostaglandin (PG) E2 and 6-keto-PGF1 alpha in the
      peritoneal exudate. Indomethacin inhibited the exudation of plasma. The levels of
      ETX in the arterial and portal venous plasmas began to increase 5 min after the
      intraperitoneal injection of ETX, and reached levels on the order of micrograms
      per milliliter plasma 10-20 min after the injection. The levels of ETX in the
      right and left thoracic lymph nodes, but not in the mesenteric lymph nodes,
      increased in parallel with those in the systemic arterial plasma. In conclusion,
      the delayed hypotension may be attributable to the mesenteric vasodilatation
      induced by PGs generated in the peritoneal cavity, and the ETX injected entered
      the systemic circulation mainly through lymphatic vessels, but in the initial
      stage, a part of ETX may be transmigrated into portal vein through damaged
      intestine.

PMID- 8269649
TI  - Efficacy of osmolality and ionic composition of resuscitation fluids for
      treatment of acute blood loss in the spontaneously hypertensive rat (SHR).
AB  - The spontaneously hypertensive rat (SHR) has a deficient glucose mobilization in
      response to blood loss. Treatment of blood loss with hypertonic glucose might
      consequently be advantageous in SHR, but the importance of osmolality as compared
      to ionic composition of resuscitation fluids is still not fully elucidated.
      Therefore, SHR (n = 32) were subjected to hemorrhage (30% of calculated blood
      volume) followed by treatment with (1) hypertonic saline (HS; 4.5 ml/kg of 7.5%
      NaCl, 2,400 mOsm/L), (2) hypertonic glucose (HG; 4.5 ml/kg of 42.3% solution,
      2,400 mOsm/L), and (3) normal saline (NS; 37.5 ml/kg of 0.9% NaCl) to provide an
      equal sodium load as with HS. All fluid regimens increased (P < 0.001 vs.
      control) mean arterial pressure (MAP). Hemodilution was more pronounced after HS
      and NS than after HG. Hypernatremia was evoked by HS. The hyperglycemic response
      to hemorrhage was intensified by HG, but it was accompanied by increased blood
      lactate levels. All three treatment regimens prolonged posthemorrhagic times
      until death (P < 0.01-0.05) (mean values: NS 363 min; HS 170 min; HG 146 min;
      nontreated controls 60 min). It is concluded, on the basis of hemodynamic,
      metabolic, and times-until-death data, that although treatment with small-volume
      HS seems superior to small-volume HG, an equal load of sodium given as NS is more
      effective for resuscitation after blood loss than HS in SHR.

PMID- 8269650
TI  - Anomalous inferior vena cava mimicking aortic dissection on transesophageal
      echocardiography.

PMID- 8269651
TI  - Vascular events responsible for thrombotic occlusion of a blood vessel.
AB  - In summary, the sequence of endothelial plaque disruption, platelet activation,
      and thrombogenic factors--that is, the balance between the thrombolytic system
      and the coagulation system--determine which blood vessel will thrombose and which
      vessel will remain patent. It seems to me that although the soft plaque with the
      thin cap and lipid core laden with oxidized LDL-activated macrophages is more
      prone to rupture than the calcified, hard plaque, it is also the plaque that may
      regress when the patient is treated aggressively with lipid-lowering or
      antioxidant therapy. In addition, drugs that lower blood pressure and heart rate
      may also decrease the tendency of the "vulnerable" plaque to rupture by
      attenuating fatigue failure. Current and future research should be directed at
      identifying vulnerable plaques in the individual patient, so that measures can be
      taken to prevent plaque rupture.

PMID- 8269652
TI  - Head-upright tilt table testing for recurrent, unexplained syncope.
AB  - Recurrent episodes of unexplained syncope are a common and often frustrating
      problem for the practicing physician. Although vasovagally mediated episodes of
      hypotension and bradycardia have been felt to be a common cause of these
      idiopathic events, traditionally this was a diagnosis of exclusion. Recently,
      head-upright tilt table testing has emerged as a method both for confirming the
      diagnosis of vasovagal syncope and for better understanding the mechanisms by
      which these events occur. This paper reviews current understanding of the
      pathophysiology of vasovagal syncope, the development and role of head-upright
      tilt table testing in its evaluation, and potential therapeutic modalities that
      can be helpful for the prevention of recurrent episodes.

PMID- 8269653
TI  - Magnesium and the heart: antiarrhythmic therapy with magnesium.
AB  - Magnesium is an essential transmembrane and intracellular modulator of the
      electrical activity of cardiac cells. This review provides an up-to-date
      consideration of the cellular and clinical electrophysiological role of
      magnesium. This ubiquitous element seems to be important from both the
      theoretical and clinical point of view, because magnesium salts (MgSO4, MgCl2)
      administered intravenously are particularly effective in those arrhythmias in
      which the mechanism involves early or delayed after depolarization-induced
      triggered activity. The authors share the view that I.V. magnesium is the drug of
      choice in "torsade de pointes" ventricular tachycardia accompanying acquired long
      QT/QTU syndrome. It is complementary therapeutic agent in digitalis-induced
      tachycardias. Further studies are needed to elucidate magnesium's mode of action
      and efficacy in other types of clinical tachyarrhythmias.

PMID- 8269654
TI  - Quality of life and circadian variation of heart rate and heart rate variability
      in short-term survivors and nonsurvivors after acute myocardial infarction.
AB  - The purpose of this study was the simultaneous examination of the quality of life
      and changes in heart rate (HR) variables of patients immediately following acute
      myocardial infarction (AMI). Quality of life, estimated on a rating scale
      assessing the patients' well-being, as well as the circadian rhythm of their HR
      and HR variability, were determined within the first 3 days and at approximately
      3 weeks after admission and the results were related to survival. The quality of
      life within the first 3 days post AMI was low in both the surviving (n = 42) and
      the nonsurviving (n = 5) patients but only the scores of the survivors increased
      significantly over the following three weeks. The HR of the survivors, initially
      lower than that of the nonsurvivors, decreased significantly at 3 weeks and a
      normal circadian pattern had developed. The HR variability of the survivors
      within the first 3 days was significantly higher than that of the nonsurvivors
      and had developed a clear circadian pattern after 3 weeks. It is concluded that
      in patients with AMI such diverse clinical aspects as quality of life and
      circadian patterns of HR and HR variability can be assessed meaningfully
      immediately post AMI and may find common expression in changes in sympathovagal
      balance.

PMID- 8269655
TI  - Evolution of cardiac changes in young insulin-dependent (type 1) diabetic
      patients--one more piece of the puzzle of diabetic cardiopathy.
AB  - Based on our recent reports that increased myocardial contractility has been
      found in newly diagnosed diabetic patients, and that diastolic (D) dysfunction
      precedes systolic (S) dysfunction, we suggested that the development of diabetic
      cardiopathy passes through the following stages: (I) increased myocardial
      contractility, (II) intact S and D function, (III) intact S function and D
      dysfunction, and (IV) S and D dysfunction. The aim of this pilot study was to
      test this hypothesis. One hundred fifty-seven young (26.2 +/- 7.4 years) cardiac
      asymptomatic patients with type I diabetes and 54 healthy subjects were studied
      using M-mode echocardiography. The presence of at least one of the variables for
      systolic function (ejection fraction, mean velocity of circumference, fiber
      shortening, and stroke index) or diastolic function [left atrium emptying index
      (LAEI), EFo slope of anterior mitral leaflet, and isovolumetric relaxation time
      (IRT)] outside the control mean +/- 2 SD was interpreted as an increased or
      depressed myocardial contractility, and diastolic dysfunction, respectively. The
      severity of diabetic complications (retinopathy, nephropathy, and cardiac
      autonomic neuropathy) was evaluated by the diabetic complication index (DCI = 0
      divided by 6 scores). Our hypothesis was confirmed significantly (p < 0.001) in
      148 (94%) patients with diabetes. Duration of diabetes and DCI progressed
      significantly (ANOVA: F = 36.6, p < 0.001; F = 70.8, p < 0.001) with hypothetical
      stages. Diastolic dysfunction was more pronounced in stage IV than in stage III:
      IRT (80.5 +/- 18.6 ms vs. 62.5 +/- 16.4, p < 0.001), EFo (63 +/- 15 mm/s vs. 72
      +/- 21, p < 0.05), LAEI (0.58 +/- 0.13 vs. 0.8 +/- 0.15, p < 0.001).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8269656
TI  - The effect of extracorporeal high blood flow rate on left ventricular function
      during hemodialysis--an echocardiographic study.
AB  - The effect of increased extracorporeal blood flow rate on left ventricular (LV)
      function has been studied during volume-controlled bicarbonate hemodialysis. Ten
      stable patients on chronic hemodialysis, with a mean age of 28 years (range 19
      38) were studied using two-dimensional and Doppler echocardiography. The mean
      time on hemodialysis was 32 months (range 3-60). All patients were investigated
      during three dialysis sessions on the first day of the week for 3 consecutive
      weeks. The blood flow rate was chosen randomly as 250, 350, or 450 cc/min. Apart
      from the time of hemodialysis and blood flow rate, other parameters of the
      hemodialysis were kept stable during all three sessions. Echocardiographic
      studies were done before, at mid dialysis, and during the last 15 min of each
      dialysis session. The following parameters were evaluated: heart rate, mean blood
      pressure, shortening fraction, ejection fraction, cardiac output, and pre
      ejection period/LV ejection time ratio. The changes of the measured cardiac
      parameters at the beginning, middle and end of each session were not
      significantly different. Furthermore, the differences in changes between the
      three different sessions were comparable. Our results indicate that an increase
      in dialysis blood flow rate up to 450 cc/min does not have an adverse effect on
      the left ventricle in patients on maintenance hemodialysis and with stable
      cardiovascular function.

PMID- 8269657
TI  - Different pressure gradients can be produced in a fixed stenosis--an in vitro
      study.
AB  - An in vitro study was conducted, using a stenotic model to demonstrate that
      different pressure gradients can be produced by the same degree of valvular
      stenosis. This model is comprised of two cylindric chambers with a diaphragm in
      the center which had a small central hole. An injector was connected to one end
      of the prestenotic chamber to produce a steady pulsed flow. A rubber tube was
      connected to the other end of the poststenotic chamber and led upward to a large
      reservoir which provided a constant afterload pressure. Two pressure transducers
      were attached to the two connecting tubes, both linked with two pigtail catheters
      which were accommodated in the chambers just before and after the stenotic
      diaphragm. Two sets of injection volumes (20 and 30 ml) and multiple injections
      with different flow rates (5, 10, 15,...49 ml/s) were administered and resulting
      pressures measured by the two transducers were recorded. Results showed that
      different pressure gradients could be produced using the same injection volume,
      the same afterload, and the same degree of stenosis. The greater the flow rate,
      the higher the pressure gradient. Good correlation existed between the pressure
      gradient and the injection flow rate (r = 0.95 and 0.97 for the study groups
      receiving 20 and 30 ml injection volumes, respectively; p < 0.001 in all
      comparisons). Thus, a higher pressure gradient may not necessarily indicate a
      severe degree of valvular stenosis. Evaluation of a stenotic lesion should not be
      made from the degree of pressure gradient alone--other hemodynamic conditions
      should also be taken into account.

PMID- 8269658
TI  - The heart in polymyositis: a prospective evaluation of 26 patients.
AB  - Although cardiac abnormalities have been reported in patients with idiopathic
      polymyositis-dermatomyositis (PM), the nature and extent of these abnormalities
      have varied. The purpose of this study was to determine the prevalence and to
      obtain a better description of the spectrum of cardiac abnormalities in a cohort
      of patients with PM by use of a thorough noninvasive cardiac evaluation.
      Accordingly, we studied 26 patients with a history of PM and clinically inactive
      myositis (22 polymyositis, 4 dermatomyositis) between June 1984 and June 1991.
      Examination included history, physical examination, 12-lead electrocardiography,
      24-h ambulatory electrocardiographic monitoring, chest radiography, transthoracic
      echocardiography, and radionuclide ventriculography. Of the patients studied, 77%
      were taking corticosteroid medications at a mean dose of 39 +/- 27 mg at the time
      of their evaluation. All 26 patients were identified as having two or more
      cardiac abnormalities. Cardiac symptoms and signs were common (62 and 81%,
      respectively), but were generally nonspecific. Electrocardiographic findings were
      most common (in 85% of cases), followed by findings on ambulatory monitoring
      (77%), echocardiography (42%), and radionuclide ventriculography (15%). The
      prevalence of mitral valve prolapse (8%) and hyperkinetic left ventricular
      contraction (12%) was significantly lower than previously reported. A secondary
      aim of this study was to determine associations between demographic variables
      including age, disease duration, cardiovascular symptoms, immunosuppressive
      therapy, autoantibody status, and creatinine phosphokinase level, and the
      presence of cardiac abnormalities. Of these patient variables, only increasing
      patient age was associated with an increased likelihood of cardiac abnormalities
      on noninvasive testing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269659
TI  - Beta-blocker infusion did not improve left ventricular diastolic function in
      myocardial infarction: a Doppler echocardiography and cardiac catheterization
      study.
AB  - Left ventricular (LV) diastolic function changes after myocardial infarction. It
      has been suggested that beta blockers may improve diastolic function in
      hypertensive and heart failure patients. Doppler echocardiographic filling
      patterns and invasive hemodynamic indices have been used to analyze LV diastolic
      function. To determine the effect of beta blockers on LV diastolic function, we
      studied 32 patients with anterior wall myocardial infarction with a mean age of
      53 years. Peak early and late flow velocities, peak early-to-late flow velocities
      ratio, pressure half time, diastolic filling period, isovolumic relaxation time,
      cardiac index, mean arterial pressure, wedge pressure, and systemic and pulmonary
      vascular resistance indices were obtained simultaneously before and after an
      intravenous infusion of 10 mg of atenolol. Cardiac index decreased from 4.27 +/-
      0.97 to 3.19 +/- 0.91 l/min/m2 (p = 0.0001); mean arterial pressure decreased
      from 85 +/- 10 to 80 +/- 11 mmHg (p = 0.004); wedge pressure increased from 11 +/
      5 to 13 +/- 4 mmHg (p = 0.002); systemic vascular resistance index increased
      from 1586 +/- 409 to 1980 +/- 634 dyn.m2.s/cm5 (p = 0.0002); pulmonary vascular
      resistance index increased from 115 +/- 58 to 163 +/- 72 dyn.m2.s/cm5 (p =
      0.0004); peak late flow velocity decreased from 64 +/- 15 to 49 +/- 14 cm/s (p =
      0.0001); early-to-late ratio increased from 0.95 +/- 0.35 to 1.29 +/- 0.36 (p =
      0.0001); diastolic filling period increased from 300 +/- 108 to 400 +/- 110 ms (p
      = 0.0001) and isovolumic relaxation time increased from 133 +/- 29 to 143 +/- 29
      ms (p = 0.009). No significant changes were observed for peak early flow velocity
      and pressure half-time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269660
TI  - Assessment of right ventricular diastolic filling in patients with coronary
      artery disease.
AB  - To assess right ventricular (RV) diastolic filling in coronary artery disease
      (CAD), with special reference to the involved lesions of the coronary arteries
      and left ventricular (LV) systolic function, gated radionuclide ventriculography
      was performed at rest in 106 patients with single-vessel CAD. Based on the site
      of coronary arterial involvement, patients were classified into three groups:
      left anterior descending CAD, right CAD, and left circumflex CAD. Patients in
      each group were further subdivided according to normal or decreased LV ejection
      fraction, resulting in six groups. Seventeen normal subjects were examined as a
      control group. Time-activity and its first-derivative curves were computed for
      the right and left ventricles. RV systolic function was normally preserved in all
      six groups, even when LV systolic function was damaged severely. The ratio of
      peak RV filling rate to peak RV ejection rate was significantly decreased in all
      six groups compared with that in control subjects, indicating that RV filling was
      impaired in patients with CAD. The ratio was below the lower limit of normal in
      14 (23%) of 62 patients with normal LV systolic function and in 13 (30%) of 44
      patients with impaired LV systolic function. None of the control subjects showed
      a decreased ratio of peak RV filling rate to peak RV ejection rate. Thus, in
      patients with CAD, RV filling is impaired, which may be independent of the site
      of coronary arterial involvement and of the LV or RV systolic function.

PMID- 8269661
TI  - Unplanned admissions after outpatient cardiac catheterization.
AB  - Increasing numbers of patients are undergoing diagnostic catheterization as
      outpatients; however, a small proportion of patients requires hospital admission
      following the procedure. Unplanned admissions after consecutive outpatient
      cardiac catheterizations performed during 1 year were prospectively reviewed to
      determine the incidence of and reasons for admission. Among 847 patients
      undergoing outpatient cardiac catheterization, 130 patients (15%) required
      hospital admission after the procedure. Admitted patients were divided into four
      groups: patients undergoing immediate percutaneous transluminal coronary
      angioplasty (PTCA) (Group 1; 33%), patients with severe cardiac disease requiring
      urgent intervention (Group 2; 48%), patients suffering complications or
      hemodynamic instability (Group 3; 15%), and patients whose procedures were
      completed too late to allow same-day discharge (Group 4; 4%). Patients over 65
      were more likely to require admission and women were more likely to be admitted
      with complications or hemodynamic instability. Findings are compared with results
      of other outpatient series, and implications regarding appropriate setting for
      outpatient catheterization are discussed.

PMID- 8269662
TI  - The implantable defibrillator and antiarrhythmic drugs--competitive and
      complementary treatment for severe ventricular arrhythmia.
AB  - Most patients with a history of sustained ventricular tachycardia (VT) or
      ventricular fibrillation (VF) are at high risk of recurrence. Implanted
      defibrillators (ICDs) are highly effective in sensing and converting VT or VF to
      a perfusing rhythm. "Conventional" antiarrhythmic agents, which primarily block
      cardiac sodium channels, are relatively ineffective in preventing arrhythmia
      recurrence; amiodarone and sotalol appear to be effective in reducing recurrence
      and mortality rates, although the extent of benefit is not well understood.
      Despite the apparent advantage of ICDs, they have short- and long-term
      complications, are costly, and their benefit in prolonging the quantity or
      quality of life remains unproven. Randomized clinical trials which compare the
      effect of ICDs with that of antiarrhythmic drugs on mortality, cost, and quality
      of life will be necessary to understand how patients with malignant arrhythmias
      ought to be treated. If an ICD is implanted, adjunctive therapies need to be
      considered to treat the underlying heart disease and to derive optimum benefit
      from the device. Drugs may have beneficial or adverse interactions with devices,
      and the full understanding of these interactions requires further study.

PMID- 8269663
TI  - Cor pulmonale caused by recurrent pulmonary emboli.
AB  - A 53-year-old black man developed femoral thrombophlebitis in 1983 following a
      Harrington nail implantation in his first lumbar vertebral region. There was
      evidence of pulmonary embolization at that time and recurrently until he
      developed ventricular fibrillation and died in 1987. The terminal event followed
      a hypotensive episode during the course of a right ventricular catheterization.
      Autopsy confirmed the clinical impression that he had multiple recurrent
      thromboemboli to his lungs. After several years of embolization, the pulmonary
      arterial circulation was sufficiently occluded to result in pulmonary
      hypertension. Cor pulmonale was produced, with congestive heart failure leading
      to a progressively downhill course in the 4 months before his death.

PMID- 8269664
TI  - Coronary artery fistula related to dilatation of totally occluded vessel.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) is widely used to treat
      patients with coronary artery disease. Experience and improvement in catheters
      has led to its wider utilization. A case of coronary recanalization, complicated
      by coronary fistula created by an angioplasty guidewire, is reported.

PMID- 8269665
TI  - A case of tachycardia-induced cardiomyopathy due to chronic ectopic atrial
      tachycardia.
AB  - Only a few reports exist that chronic supraventricular tachycardia causes
      ventricular dilation and poor left ventricular contraction--so-called
      "tachycardia-induced cardiomyopathy." Clinical and electrophysiologic features of
      chronic supraventricular tachycardia including chronic persistent ectopic atrial
      tachycardia (EAT) in adults have also been described by a few investigators. We
      report a rare case of long follow-up of chronic EAT-induced severe cardiomyopathy
      and mitral regurgitation that was well controlled after medical treatment.

PMID- 8269666
TI  - Profiles in cardiology: Donald Arthur McDonald.

PMID- 8269667
TI  - Myocardial infarction, thrombolytic therapy, and economics.

PMID- 8269668
TI  - Risk of cardiac surgery in patients with peripheral vascular disease.

PMID- 8269670
TI  - Owl's eye appearance of a thyroid cyst.

PMID- 8269669
TI  - Choledochal cyst. Preoperative sonographic and scintigraphic assessment.

PMID- 8269671
TI  - Renal transplantation of a horseshoe kidney.

PMID- 8269673
TI  - Surface and volume three-dimensional displays of Tc-99m HMPAO brain SPECT images
      in stroke patients by a three-headed gamma camera.
AB  - Twenty patients with strokes were studied to evaluate volume and surface three
      dimensional (3D) displays in Tc-99m HMPAO brain SPECT imaging using a triple-head
      gamma camera interfaced with a 64-bit super computer. In each patient, after an
      intravenous injection of 20 to 30 mCi of Tc-99m HMPAO, a first-pass cerebral flow
      study and brain SPECT images at 30 to 60 minutes were obtained. Although the
      cerebral lesion was more clearly delineated with surface 3D and volume 3D,
      crossed cerebellar diaschisis in seven patients was more clearly exhibited by
      volume 3D rather than surface 3D imaging. Volume and surface 3D displays enhance
      continuity of structures and understanding of spatial relationships; these
      displays view the brain from all angles, and thus the location and extension of
      lesion(s) in the brain are much easier to appreciate. It is concluded that 1)
      both surface and volume 3D displays equally enhance SPECT interpretation; and 2)
      volume 3D display enhances demonstration of crossed cerebellar diaschisis, but
      surface 3D display does not.

PMID- 8269672
TI  - Ascending aortic dissection causing unilateral absence of perfusion on lung
      scanning.
AB  - A case of an ascending aortic dissection occurring in a patient 8 years after an
      aortic valve replacement is presented. The patient's initial clinical
      presentation was thought to be due to pulmonary embolism, and a ventilation
      perfusion lung scan demonstrated mismatched absence of perfusion to the entire
      right lung. Aortography and findings at surgery demonstrated a type A dissection
      of the ascending aorta. The anatomic relationship of the aorta and pulmonary
      artery and their common tunica adventitia make the right pulmonary artery
      susceptible to extrinsic compression after aortic dissection. Although uncommon,
      dissection of the ascending aorta needs to be considered in patients who have
      undergone previous aortic valve surgery and demonstrate mismatched unilateral
      absence of perfusion to the right lung. Because anticoagulation is
      contraindicated in patients with acute aortic dissection, confirmation of the
      diagnosis with angiography usually is required.

PMID- 8269674
TI  - Nonvisualization of suppressed thyroid tissue on Tl-201 scintigraphy.
AB  - Tl-201 scintigraphy has been used to visualize thyroid tissue that is suppressed
      by an autonomously functioning thyroid nodule. Reports have indicated that the
      sensitivity of this technique rivals that obtained by I-123 scanning after
      thyroid-stimulating hormone stimulation. We report a case of triiodothyronine
      toxicosis caused by an autonomously functioning thyroid nodule in which the
      suppressed thyroid tissue was not visualized on Tl-201 scintigraphy. The
      suppressed tissue was readily identified with ultrasound imaging, which
      demonstrates the utility of this technique in differentiating between thyroid
      suppression and agenesis.

PMID- 8269675
TI  - Considerations of brain death on a SPECT cerebral perfusion study.
AB  - Brain death imaging is often a diagnostic challenge. Cerebral angioscintigraphy
      is extensively used for this analysis, but this test does not allow the perfusion
      evaluation of the posterior fossa. The authors report a case in which a SPECT
      study showed persistence of blood flow in infratentorial structures with total
      absence of cerebral (supratentorial) perfusion. This finding excluded the
      diagnosis of brain death.

PMID- 8269676
TI  - Vascular complication of a transjugular intrahepatic portacaval stent.
AB  - The percutaneous transjugular intrahepatic portacaval stent shunt is a
      nonsurgical approach to portosystemic shunting. The case of a large defect seen
      on a radiocolloid liver--spleen scan is attributed to a hepatic infarct related
      to the shunting procedure.

PMID- 8269677
TI  - Finding of right hepatic vein focal defect in liver scan of a patient with veno
      occlusive disease.
AB  - A 38-year-old woman hospitalized for delivery after treatment for infertility
      with lymphocyte transfusions from her husband developed severe hepatopathy. On
      the basis of findings in a hepatic specimen obtained by biopsy, the authors
      diagnosed hepatic veno-occlusive disease. In scintigrams that used Tc-99m
      phytate, a long, narrow defect was found that extended from the outer part of the
      right lobe of the liver to the junction of the hepatic veins and the inferior
      vena cava. In SPECT of the liver performed with Tc-99m phytate, the defect
      corresponded to the region of the right hepatic vein.

PMID- 8269678
TI  - Mediastinal uptake of I-131 in a hiatal hernia mimicking recurrence of papillary
      thyroid carcinoma.
AB  - I-131 is used to image patients diagnosed with papillary or follicular carcinoma
      of the thyroid after thyroidectomy to observe for metastatic disease or residual
      thyroid tissue. I-131 is excreted in gastric mucosa and is seen in the esophagus
      after the swallowing of saliva. The authors describe a patient in whom
      radiopharmaceutical activity in the mediastinum was subsequently shown to be due
      to a hiatal hernia.

PMID- 8269679
TI  - Uptake of I-131 by an abdominal neurilemoma mimicking metastatic thyroid
      carcinoma.
AB  - I-131 whole-body imaging may show characteristic findings in functioning,
      metastatic differentiated thyroid carcinoma. Nonthyroidal tumor uptake of I-131
      is rare, but may mislead the physician to inappropriate treatment. A case is
      reported of a 59-year-old woman with papillary thyroid carcinoma who demonstrated
      strong uptake of I-131 in an abdominal cystic neurilemoma. Her serum
      thyroglobulin concentration at that time was low, at 3.35 ng/ml. Although the
      concentrating mechanism of I-131 was not clear, several clues pointed to the
      possibilities of nonthyroidal tumor uptake: 1) faster clearing of radioactivity
      than usual thyroid tissue, 2) persistent low serum thyroglobulin concentration,
      and 3) the presence of a cystic component in the nonthyroidal tumor.

PMID- 8269680
TI  - Remnants of normal tissue in polycystic disease of the liver. A cause for
      difficulty in the interpretation of indium-111 white blood cell study.
AB  - On In-111 WBC images, diffuse homogeneous uptake of the radiopharmaceutical
      should be present throughout the liver. The authors present a case of a febrile
      patient with polycystic liver disease in whom the normal diffuse uptake was not
      seen. Instead, the images demonstrated focal areas of uptake, which suggested
      infection. Tc-99m SC liver spleen scintigraphy demonstrated the In-111 WBC foci
      to correspond to areas of residual normal parenchyma. The patient underwent
      laparotomy and liver transplantation and no abscesses were found. Pathologic
      examination of the liver revealed multiple uninfected cysts and residual normal
      parenchyma in the caudate lobe, corresponding to the findings on scintigraphy.

PMID- 8269681
TI  - Nomograms of renal length in children obtained from DMSA scintigraphy.
AB  - The aim of this study was to establish nomograms of renal length in children
      comparing age, body weight, and height. Renal lengths were obtained from data
      derived from Tc-99m DMSA scintigraphy in 266 patients with 532 kidneys that
      appeared normal on DMSA studies. The children's ages ranged from 6 days to 19
      years. Renal length appeared to have nonlinear relationships with patient weight
      and age, but was found to correlate linearly with patient height. On average,
      scintigraphic renal length exceeded sonographic renal length by approximately 1
      cm. The most likely explanation for this is the effect of respiration causing
      renal motion during the acquisition of the scintigraphic images. It is hoped that
      the nomograms derived from these data will be of use in routine clinical practice
      for nuclear medicine departments performing DMSA scintigraphy in children.

PMID- 8269682
TI  - Enlarged photon-deficient area in expected site of renal allograft on Tc-99m DTPA
      study. A sign of renal vein thrombosis.
AB  - Tc-99m DTPA renal imaging has been routinely used in postrenal transplant
      evaluation. A patient's Tc-99m DTPA studies after transplantation are presented,
      showing a large photon-deficient area in the region of the allograft on the third
      postoperative day. The photon-deficient area is two to three times larger than
      that seen in the original, functioning allograft on the first postoperative day.
      Enlarged to a weight of 530 g, the allograft on gross and microscopic examination
      confirmed renal vein thrombosis. Enlargement of the photon-deficient area at the
      anatomic site of the allograft indicates a scintigraphic pattern of renal vein
      occlusion incompatible with a viable allograft.

PMID- 8269683
TI  - Dermatofibrosarcoma protuberans of the toe. Findings on multiple imaging
      modalities.
AB  - Dermatofibrosarcoma protuberans occurs early in life, is an unusual soft tissue
      tumor, and is uncommonly seen distal to knees. The authors present a rare case of
      dermatofibrosarcoma protuberans of the toe with different imaging modalities.

PMID- 8269684
TI  - Thyroid scintigraphy of hyperthyroxinemia.
AB  - The term "hyperthyroxinemia" encompasses clinical syndromes associated with
      elevated levels of thyroid hormone in the presence of increased, normal, or
      decreased thyroid function. The clinical presentation (i.e., history and physical
      examination), in vitro thyroid function tests, as well as radioisotope thyroid
      imaging all play key roles in the diagnosis of the underlying thyroid disorder.
      Many of these disorders and their appearance on thyroid scintigraphy are
      presented in this atlas.

PMID- 8269685
TI  - Scintigraphic evaluation of a patient with hemangiosarcoma. Labeled red blood
      cell imaging is nondiagnostic.

PMID- 8269686
TI  - Retrocaval ureter in newborn demonstrated by Tc-99m DTPA renal scintigram.

PMID- 8269687
TI  - Scintigraphic findings of coexisting renal artery stenosis and renal vein
      thrombosis.

PMID- 8269688
TI  - The lung scan appearance of a "coughed-up" endobronchial tumor.

PMID- 8269689
TI  - Gastroparesis associated with muscular dystrophy.

PMID- 8269690
TI  - A comparison of indium-111 leukocyte and gallium-67 scintigraphy in a patient
      with a myocardial abscess.

PMID- 8269691
TI  - Pediatric AIDS-related myocarditis: focal cardiac gallium uptake.

PMID- 8269692
TI  - Women's health: a Washington, D. C. perspective.

PMID- 8269693
TI  - More OSHA questions and answers. Most frequently asked questions concerning the
      Blood-borne Pathogens Standard.

PMID- 8269694
TI  - M.I. provider profiles.

PMID- 8269695
TI  - Additional AIDS surveillance case definition.

PMID- 8269696
TI  - Basic-level individuals.
AB  - In this experiment, 4-year-old children interpreted a novel count noun taught
      ostensively for an unfamiliar object as referring to a basic-level kind (such as
      PERSON or DOG) rather than to a kind that individuates its members by type of
      situation (such as PASSENGER or PUPPY). Because ostension does not distinguish a
      basic-level kind from a situation-restricted kind, this finding suggests that
      children assume, as a default, reference to a basic-level kind rather than to a
      situation-restricted kind when they hear a count noun applied to an unfamiliar
      object in an ostensive definition. The experiment shows that the assumption
      guides children's interpretation only if the object is unfamiliar, and if no
      specific information is available calling for a situation-restricted kind
      interpretation. The proposed word-learning assumption is critical to an
      understanding of the psychologically privileged manner of individuation, and
      therefore, of quantification (e.g., counting) involving objects.

PMID- 8269697
TI  - Neural networks, nativism, and the plausibility of constructivism.
AB  - Recent interest in PDP (parallel distributed processing) models is due in part to
      the widely held belief that they challenge many of the assumptions of classical
      cognitive science. In the domain of language acquisition, for example, there has
      been much interest in the claim that PDP models might undermine nativism. Related
      arguments based on PDP learning have also been given against Fodor's anti
      constructivist position--a position that has contributed to the widespread
      dismissal of constructivism. A limitation of many of the claims regarding PDP
      learning, however, is that the principles underlying this learning have not been
      rigorously characterized. In this paper, I examine PDP models from within the
      framework of Valiant's PAC (probably approximately correct) model of learning,
      now the dominant model in machine learning, and which applies naturally to neural
      network learning. From this perspective, I evaluate the implications of PDP
      models for nativism and Fodor's influential anti-constructivist position. In
      particular, I demonstrate that, contrary to a number of claims, PDP models are
      nativist in a robust sense. I also demonstrate that PDP models actually serve as
      a good illustration of Fodor's anti-constructivist position. While these results
      may at first suggest that neural network models in general are incapable of the
      sort of concept acquisition that is required to refute Fodor's anti
      constructivist position, I suggest that there is an alternative form of neural
      network learning that demonstrates the plausibility of constructivism. This
      alternative form of learning is a natural interpretation of the constructivist
      position in terms of neural network learning, as it employs learning algorithms
      that incorporate the addition of structure in addition to weight modification
      schemes. By demonstrating that there is a natural and plausible interpretation of
      constructivism in terms of neural network learning, the position that nativism is
      the only plausible model of acquisition can no longer be defended. Indeed, I
      briefly discuss a number of learning-theoretic reasons indicating that
      constructivist models so characterized uniquely possess a number of important
      learning characteristics.

PMID- 8269698
TI  - Resolution of quantifier scope ambiguities.
AB  - Various processing principles have been suggested to be governing the resolution
      of quantifier scope ambiguities in sentences such as Every kid climbed a tree.
      This paper investigates structural principles, that is, those which refer to the
      syntactic or semantic positions of the quantified phrases. To test these
      principles, the preferred interpretations for three grammatical constructions
      were determined in a task in which participants made speeded judgments of whether
      a sentence following a doubly quantified sentence was a reasonable discourse
      continuation of the quantified sentence. The observed preferences cannot be
      explained by any single structural principle, but point instead to the
      interaction of several principles. Contrary to many proposals, there is little or
      no effect of a principle that assigns scope according to the linear order of the
      phrases. The interaction of principles suggests that alternative interpretations
      of the ambiguity may be initially considered in parallel, followed by selection
      of the single interpretation that best satisfies the principles. These results
      are discussed in relation to theories of ambiguity resolution at other levels of
      linguistic representation.

PMID- 8269699
TI  - Reading acquisition and phonemic awareness testing: how conclusive are data from
      Down's syndrome? (Remarks on Cossu, Rossini, and Marshall, 1993).

PMID- 8269700
TI  - Learning to read in the absence of phonemic awareness? A comment on Cossu,
      Rossini, and Marshall (1993).

PMID- 8269701
TI  - What lesson for dyslexia from Down's syndrome? Comments on Cossu, Rossini, and
      Marshall (1993).

PMID- 8269702
TI  - A physical model for the time-dependent deformation of articular cartilage.
AB  - A physical analogue was developed to simulate the time-dependent deformation of
      articular cartilage. The analogue was constructed from a matrix of water
      saturated sponge material whose permeability could be varied, and was constrained
      so as to allow one-dimensional deformation under both static and dynamic
      compressive loading. Simultaneous measurements were made of the applied stress,
      matrix excess pore pressure and matrix strain. The results obtained reinforce the
      view that under static and low strain-rate loading conditions, a consolidatable
      system like cartilage sustains the applied stress through a stress-sharing
      mechanism between matrix water and the solid skeleton. However, at high strain
      rates load-bearing is dominated by a mechanism in which the matrix water is
      immobilized and the excess pore pressure rises to almost that of the applied
      stress, thus suggesting that the constituents of the matrix act as a single
      functional entity to support the applied load. The model supports the description
      of cartilage as a poro-visco-hyperelastic material.

PMID- 8269703
TI  - A high sensitivity dot-blot assay for proteoglycans by cuprolinic blue
      precipitation.
AB  - A highly sensitive blot-assay was developed for glycosaminoglycans (GAGs) and
      proteoglycans (PGs) utilizing a precipitation reaction by a cationic dye
      Cuprolinic Blue. The precipitates were deposited into 1-2 mm2 spots on
      nitrocellulose membrane by using a 96-well filtration apparatus. The dried sheet
      was digitized by a flat bed scanner and the intensity of the dots was quantitated
      by an image analysis software. The working range for chondroitin sulfate was 10
      300 ng. The response of various GAGs differed according to the number of anionic
      groups, both sulphate and carboxyl groups being able to bind the dye. The
      sensitivity of the assay was decreased by high concentrations of GuC, CsC and
      protein, but not by nonionic detergents, common buffers and 8 M urea. Contact
      exposure to autoradiography film enabled quantitation of 25-250 DPM, and 1-10
      DPM, of 35SO4-radioactivity in precipitated PGs after overnight and 14 days'
      exposures, respectively.

PMID- 8269704
TI  - Hsp 47 is localized to regions of type I collagen production in developing murine
      femurs and molars.
AB  - To determine whether the proposed molecular chaperone Hsp47 is associated with
      the production of heterotrimeric procollagen, the distribution of anti-Hsp47 and
      anti-collagen antibodies were examined in developing murine femurs and molars of
      22-23-day CD-1 mice. In addition, the expression of Hsp47, and collagen mRNAs
      were assessed by in situ hybridization using oligonucleotide probes. These
      studies revealed that Hsp47 was developmentally expressed and produced in regions
      that are coincident with type I collagen. Hsp47 was not localized in
      cartilaginous zones of developing femurs or in the regions of developing molars
      producing type III collagen. These results support the hypothesis that Hsp47 is
      necessary for the assurance of type I procollagen and is not expressed with other
      homotrimeric procollagen molecules.

PMID- 8269705
TI  - Articular cartilage explant culture; an appropriate in vitro system to compare
      osteoarthritic and normal human cartilage.
AB  - Proteoglycan metabolism of normal and histologically mild to moderate
      osteoarthritic cartilage explants were studied. Explants were obtained from the
      human knee of donors aged over 40 years. Proteoglycan content, synthesis and
      release were very similar in normal cartilage obtained from donors with focal
      osteoarthritis and cartilage obtained from donors without any sign of
      osteoarthritis. This suggests that cartilage obtained from donors with focal
      osteoarthritis indeed can be considered as "normal". The relatively large surface
      area-compared to their natural setting in the joint- of cartilage explants in
      culture did not affect the parameters measured, as there was a strong linear
      correlation between these parameters and the weight of the explants. From our
      results, we conclude that the use of full depth cartilage tissue explants is a
      reliable way to assess and compare proteoglycan content, synthesis and release in
      normal and osteoarthritic cartilage from the same donor.

PMID- 8269706
TI  - Quantitation of lung elastin and collagen in protein and essential fatty acid
      malnourished rats.
AB  - Thirty-nine 40-day old male Sprague-Dawley rats (average wt. 115g) were divided
      into 4 groups and fed diets A, control; B, essential fatty acid (EFA) deficient;
      C, protein deficient; D, combined protein and EFA deficient. At the end of 5
      weeks, lungs were removed from the animals for collagen and elastin quantitation
      and for morphometric measurements. The collagen content of the lungs which ranged
      from 95-100 micrograms/mg dried fat-free (D.F.F.) tissue, was not altered by
      protein or EFA deficiencies. The elastin content of lungs was markedly increased
      in diets C and D while the cross-linking (Isodesmosine-desmosine content)
      expressed as residues per 1,000 (R/1000) was not different in the four groups.
      The elastin content of lungs from group D animals was greater than group C
      suggesting an additive effect from the EFA deficiency in diet D. The morphometric
      measurements indicated no change in alveolar linear diameter (Lm) while the total
      alveolar surface area (ISAA1V) was decreased by the deficient diets C and D. The
      protein deficiency and the combined protein and EFA deficiencies produced an
      increased elastin content in lung. Elastin cross-linking and collagen quantity
      was not affected by the dietary treatments. The morphometric measurements
      indicated that protein deficiency in these animals did not produce structural
      changes in the lungs as indicated by alveolar dimensions.

PMID- 8269707
TI  - Ultrastructural alterations of collagen fibrils in blood vessel walls.
AB  - With increasing concern for elucidation of the role of connective tissues in
      degenerative diseases of blood vessels, an ultrastructural study was conducted on
      collagen fibrils of intimal proliferation in experimental autogenous venous pouch
      aneurysms in rabbits and in atherosclerotic human arteries. The fibrils were
      compared morphometrically with adventitial collagen as controls. In intimal
      proliferation from both species intimal collagen fibrils displayed increased
      variation in shape and size when compared to adventitial collagen fibrils. The
      abnormal fibrils resembled those of inherited connective tissue diseases,
      indicating that the changes in collagen fibrils can be acquired and that
      hemodynamic stress is likely to contribute to their occurrence.

PMID- 8269708
TI  - Fundamental sources of error and spectral broadening in Doppler ultrasound
      signals.
AB  - Analysis of the signals, spectra and error bounds for Doppler ultrasound signals
      is challenging and involves numerous concepts in signal analysis, probability,
      acoustics, and fluid mechanics. Nonetheless, the results of this analysis must be
      accessible to both engineers and clinicians who work with ultrasound technology.
      The engineer who designs, builds, or maintains equipment must know whether
      specific artifacts are fundamental or can be eliminated. The clinician must be
      able to interpret whether specific signal features accurately represent the flow
      field or result from limitations of Doppler ultrasound. This article reviews
      recent advances in both conceptual and numerical models of the Doppler ultrasound
      process, and relates these advances to practical aspects such as spectral
      broadening, velocity estimation error, and data analysis error. It then reviews
      recent innovations in system implementation and signal analysis which are
      indicative of the future potential of Doppler ultrasound instrumentation.

PMID- 8269709
TI  - Evolution and taxonomy of positive-strand RNA viruses: implications of
      comparative analysis of amino acid sequences.
AB  - Despite the rapid mutational change that is typical of positive-strand RNA
      viruses, enzymes mediating the replication and expression of virus genomes
      contain arrays of conserved sequence motifs. Proteins with such motifs include
      RNA-dependent RNA polymerase, putative RNA helicase, chymotrypsin-like and papain
      like proteases, and methyltransferases. The genes for these proteins form
      partially conserved modules in large subsets of viruses. A concept of the virus
      genome as a relatively evolutionarily stable "core" of housekeeping genes
      accompanied by a much more flexible "shell" consisting mostly of genes coding for
      virion components and various accessory proteins is discussed. Shuffling of the
      "shell" genes including genome reorganization and recombination between remote
      groups of viruses is considered to be one of the major factors of virus
      evolution. Multiple alignments for the conserved viral proteins were constructed
      and used to generate the respective phylogenetic trees. Based primarily on the
      tentative phylogeny for the RNA-dependent RNA polymerase, which is the only
      universally conserved protein of positive-strand RNA viruses, three large classes
      of viruses, each consisting of distinct smaller divisions, were delineated. A
      strong correlation was observed between this grouping and the tentative
      phylogenies for the other conserved proteins as well as the arrangement of genes
      encoding these proteins in the virus genome. A comparable correlation with the
      polymerase phylogeny was not found for genes encoding virion components or for
      genome expression strategies. It is surmised that several types of arrangement of
      the "shell" genes as well as basic mechanisms of expression could have evolved
      independently in different evolutionary lineages. The grouping revealed by
      phylogenetic analysis may provide the basis for revision of virus classification,
      and phylogenetic taxonomy of positive-strand RNA viruses is outlined. Some of the
      phylogenetically derived divisions of positive-strand RNA viruses also include
      double-stranded RNA viruses, indicating that in certain cases the type of genome
      nucleic acid may not be a reliable taxonomic criterion for viruses. Hypothetical
      evolutionary scenarios for positive-strand RNA viruses are proposed. It is
      hypothesized that all positive-strand RNA viruses and some related double
      stranded RNA viruses could have evolved from a common ancestor virus that
      contained genes for RNA-dependent RNA polymerase, a chymotrypsin-related protease
      that also functioned as the capsid protein, and possibly an RNA helicase.

PMID- 8269710
TI  - Clathrin: its role in receptor-mediated vesicular transport and specialized
      functions in neurons.
AB  - Clathrin constitutes the coat of vesicles involved in three receptor-mediated
      intracellular transport pathways; the export of aggregated material from the
      trans-Golgi network for regulated secretion, the transfer of lysosomal hydrolases
      from the trans-Golgi network to lysosomes and receptor-mediated endocytosis at
      the plasma membrane. The clathrin subunits and the other major coat constituents,
      the adaptor polypeptides, interact in specific ways to build the characteristic
      polygonal clathrin lattice and to attach the coat to integral membrane receptors.
      Both clathrin coat assembly and disassembly on the cytoplasmic side of the
      membrane are multistep processes that are regulated by the coat constituents
      themselves and by cytosolic proteins and factors. Neurons represent a cell type
      with distinct morphology and special demands on exocytic and endocytic pathways
      that requires neuron-specific constituents and modifications of clathrin-coated
      vesicles.

PMID- 8269711
TI  - Side effects of chronic lithium therapy in Hong Kong Chinese: an ethnopsychiatric
      perspective.
AB  - A biocultural study of the side effects of chronic lithium treatment among 70
      Hong Kong Chinese psychiatric patients, using a self-report 33-item checklist and
      semi-structured interviews, revealed an imperfect correspondence between
      biomedically prescribed and culturally endorsed psychotropic side effects.
      Although polydipsia and polyuria (47%) were the biomedically most 'real' side
      effects, they were not usually regarded as bothersome or translated into
      metaphors to express undesirable side effects. Complaints such as tiredness
      (38%), drowsiness (36%) and poor memory (31%) were also common but their
      frequency was significantly lower than that of normal control subjects. The item
      'loss of creativity' had no conceptual equivalent in Chinese and was usually
      misinterpreted. As no patient was aware that lithium was a metal, the side effect
      'metallic taste' was variously labelled. Contrary to Western findings, complaints
      of 'missing of highs', loss of assertiveness and fear of weight gain were rarely
      encountered. Active elicitation was required for indigenous complaints, with 38%
      of patients considering lithium to cause mild "hotness." This was readily
      neutralized by drinking more water which had a "cooling" effect. Expectedly,
      concurrent neuroleptics and antidepressants amplified most lithium side effects.
      This study affirms Western data on the biomedically universalizable effects of
      chronic lithium treatment, but also supports the thesis that culturally
      constituted cognitive styles affect patients' recognition, labelling,
      experiencing and reporting the total drug effect. Further, it demonstrates that
      the lived experience and clinical negotiation of lithium associated side effects
      reproduce, authenticate, and at times critique, core cultural and moral premises
      of Western and Chinese societies.

PMID- 8269712
TI  - Research report: susto and pesticide poisoning among Florida farmworkers.
AB  - This paper discusses research designed to investigate farmworker interpretation
      of a serious incident of pesticide poisoning, specifically, whether this incident
      was considered to precipitate the Mexican folk illness "susto." The study
      revealed that a total of 23% of the population interviewed felt that they
      definitely or possibly had developed susto as a result of the pesticide exposure.
      These patients complained of more residual symptoms from the pesticide exposure
      than did those who had been affected by the poisoning but who did not feel they
      suffered from susto. The findings have implications for medical providers working
      with these populations. A self diagnosis of "susto" may indicate that a patient
      is indeed sicker than other indicators suggest, and point to a need for increased
      follow-up.

PMID- 8269713
TI  - The Spanish translation and cultural adaptation of the Diagnostic Interview
      Schedule for Children (DISC) in Puerto Rico.
AB  - This article illustrates a comprehensive cross-cultural adaptation model used to
      translate into Spanish and to culturally adapt the Diagnostic Interview Schedule
      for Children (DISC). The process strived to identify similar phenomena to those
      identified by the original English version in a dissimilar context. To attain
      cross-cultural equivalency five important dimensions were addressed: semantic,
      technical, content, criterion and conceptual. To meet this challenge various
      steps were taken, including bilingual committee, back-translation, reliability
      and validity testing. The result is an instrument which could be used, not only
      in Puerto Rico, but also in other Spanish-speaking child and adolescent
      populations after appropriate cultural adaptations.

PMID- 8269714
TI  - Aboriginal spirituality: symbolic healing in Canadian prisons.
AB  - Symbolic healing is a complex phenomenon that is still relatively poorly
      understood. This paper documents a process of symbolic healing which is occurring
      in Canadian penitentiaries, and which involves Aboriginal offenders in cultural
      awareness and educational programs. The situation is compounded, however, by the
      existence of offenders from diverse Aboriginal cultural backgrounds with
      differing degrees of orientation to Aboriginal and Euro-Canadian cultures.
      Participants must first receive the necessary education to allow them to identify
      with the healing symbols so that healing may ensue, and both the healers and the
      patients must engage in a process of redefining their cultures in search of a
      common cultural base.

PMID- 8269715
TI  - Psychiatry and ethics: the problematics of respect for religious meanings.
AB  - Over the past two decades American psychiatrists have had to address the
      emergence of an increasingly fervent religious pluralism. Particularly in cases
      of socially controversial new religious movements (NRMs), distressed families
      have pressured psychiatrists to assess the mental state of recruits to such
      sects, often labeled "cults." At this inevitably acrimonious interface between
      family values and religious liberties, psychiatrists have for the most part
      resisted pressures to medicalize religious conversions. This article provides an
      historical review of American psychiatric response to NRMs with respect to
      nosology and practice. It introduces this response in the more general context of
      ethics and the problematics of respect for religious meanings.

PMID- 8269716
TI  - Adjuvant treatment of colorectal adenocarcinoma.
AB  - Colorectal adenocarcinoma is diagnosed in 150,000 Americans yearly, and more than
      50,000 die of this disease each year. Recently, as a result of well-controlled,
      randomized, cooperative group trials, it has been demonstrated that adjuvant
      therapy of node-positive colon cancer (stage III) and node-positive or negative
      rectal cancer (stage II or stage III) can reduce recurrence and mortality and
      significantly improve overall survival. It is now the standard of care to provide
      adjuvant chemotherapy with 5-fluorouracil and levamisole for patients with node
      positive colon cancer and provide adjuvant chemoradiotherapy with both 5
      fluorouracil and high-dose radiotherapy for patients with stage II or stage III
      rectal cancer. It is estimated that these interventions, which are readily
      tolerated, will reduce the incidence of recurrence by more than 30% in both
      patient groups at a reasonable economic and health cost. Although the ideal
      method of therapy for this type of disease is not yet firmly established, it
      appears that adjuvant therapy for node-negative stage III colon cancer may be
      effective as well. Recently completed and ongoing cooperative group trials are
      investigating different combinations of chemotherapy and radiotherapy, including
      5-fluorouracil with the biomodulator leucovorin or continuous-infusion 5
      fluorouracil with radiotherapy, and comparing different durations of therapy.
      Other trials are investigating combined modality therapy for the neoadjuvant
      treatment of locally advanced rectal cancer. New findings in the genetics of
      colon cancer are being studied as prognostic information or markers to determine
      whether there are subsets of patients who might benefit from more or less
      therapy. Randomized placebo-controlled trials have been initiated to study the
      use of aspirin as a means of colon cancer prevention in high-risk populations.
      Taken together, the recent advances in our treatment and understanding of
      colorectal adenocarcinoma have resulted in a major--albeit silent--revolution in
      therapy and give firm promise for further progress.

PMID- 8269717
TI  - New radiopharmaceuticals and new applications in medicine.
AB  - All areas of radiology are constantly evolving. At times rapid advances are made
      because new equipment or pharmaceuticals are introduced. At others the evolution
      is gradual as established procedures and techniques are refined. The following
      review of selected areas in nuclear medicine includes both dramatic changes due
      to new developments and evolutionary changes in established techniques. The first
      section reviews the development of monoclonal antibodies for use in
      radioscintigraphy of neoplastic disease. Although many articles have been written
      about this topic over the years, the clinical applications have suddenly expanded
      because the Food and Drug Administration (FDA) recently approved one monoclonal
      antibody for use in the imaging of colorectal and ovarian cancer. It is
      anticipated that a number of other antibodies will be approved for clinical
      scintigraphy of both malignant and benign disease and immunotherapy. It is
      advised that the radiologist performing nuclear medicine procedures become
      knowledgeable about this expanding area of clinical application. The second
      section reviews several new radiopharmaceuticals that are being used with
      increasing frequency for myocardial imaging. The behavior of these tracers is
      different from that of thallium, and specialized imaging techniques are required.
      Although the clinical value of these agents is still questioned by some, they are
      widely used. Familiarity with this topic is recommended. The last section reviews
      some of the radiopharmaceuticals available for renal imaging and functional
      evaluation. The relatively new technetium-labeled pharmaceutical that
      approximates the behavior of hippuran is emphasized. New applications with the
      renal cortical imaging agent technetium DMSA are also reviewed. A thorough
      knowledge of the biologic behavior of these tracers and appropriate imaging and
      measurement techniques is extremely important for their appropriate clinical use.

PMID- 8269718
TI  - Proceedings of the Inaugural Meeting of the Dysphagia Research Society.
      Milwaukee, Wisconsin, November 6-8, 1992.

PMID- 8269719
TI  - Pharyngeal structure and function.

PMID- 8269720
TI  - Central nervous system control mechanisms of swallowing: a neuropharmacological
      perspective.
AB  - Neuropharmacological in vivo and in vitro investigations are beginning to provide
      insight into chemical signaling processes within brainstem networks controlling
      the individual stages of swallowing. Different subtypes of excitatory amino acid
      (EAA) receptors operate at the level of solitarial interneurons programming the
      buccopharyngeal and esophageal stage, as well as motoneurons innervating
      esophageal striated musculature. Muscarinic cholinoceptors (MAChRs), probably
      activated via a propriobulbar input, are critically involved in generating output
      from solitarial neurons to esophageal motoneurons. Inhibition to tonically active
      GABAA-receptor mediated afferents to solitarial premotor neurons results in
      rhythmic deglutitive output, reflecting disinhibition of EAA and MACh receptor
      activity. Motoneuronal EAA receptors may be regulated by a somatostatinergic
      input arising from solitarial premotoneurons. The available evidence is
      consistent with a transmitter heterogeneity in esophageal premotor neurons that
      may operate to provide chemical coding of afferents to the motor output stage of
      the pattern generator for esophageal peristalsis.

PMID- 8269721
TI  - Control of esophageal motor function.

PMID- 8269722
TI  - Specializations of the human upper respiratory and upper digestive systems as
      seen through comparative and developmental anatomy.
AB  - The human upper respiratory, or aerodigestive, tract serves as the crossroads of
      our breathing, swallowing and vocalizing pathways. Accordingly, developmental or
      evolutionary change in any of these functions will, of necessity, affect the
      others. Our studies have shown that the position in the neck of the mammalian
      larynx is a major factor in determining function in this region. Most mammals,
      such as our closest relatives the nonhuman primates, exhibit a larynx positioned
      high in the neck. This permits an intranarial larynx to be present and creates
      largely separate respiratory and digestive routes. While infant humans retain
      this basic mammalian pattern, developmental descent of the larynx considerably
      alters this configuration. Adult humans have, accordingly, lost separation of the
      respiratory and digestive routes, but have gained an increased supralaryngeal
      region of the pharynx which allows for the production of the varied sounds of
      human speech. How this region has changed during human evolution has been
      difficult to assess due to the absence of preserved soft-tissue structures. Our
      studies have shown that the relationship between basicranial shape and laryngeal
      position in living mammals can be a valuable guide to reconstruct the region in
      ancestral humans. Based on these findings we have examined the basicrania of
      fossil ancestors--from over two million years ago to near recent times--and have
      reconstructed the position of the larynx and pharyngeal region in these early
      forms. This has allowed us insight into how our ancestors may have breathed and
      swallowed, and when the anatomy necessary for human speech evolved.

PMID- 8269723
TI  - Functional relationship of the larynx and upper GI tract.

PMID- 8269724
TI  - Noninvasive approaches to deglutitive aspiration.
AB  - Etiologies for aspiration are described. Noninvasive procedures to eliminate
      aspiration are outlined including postural techniques, variations in bolus
      volume, viscosity, taste and temperature, methods to enhance oral sensation,
      swallow maneuvers and exercise programs to improve neuromotor control for
      swallow. Specific disorders for which each procedure is appropriate are defined.

PMID- 8269725
TI  - Dynamic control of the larynx and future perspectives in the management of
      deglutitive aspiration.
AB  - The approach to deglutitive aspiration presented in this article is original. It
      permitted restoring the dynamic nature of the swallowing process in immobile
      largynges, a situation found when function has been abolished through central
      neurological deficit. The necessity, in the author's view, for a miniaturized
      electronic system bypassing the diseased centers able to produce tight glottic
      closure in a canine model during pharyngeal stimulation is emphasized. There is
      hope that we may ultimately move towards human implantation if the proposed
      electronics will be well tolerated over time.

PMID- 8269726
TI  - Manometric evaluation of the pharynx.
AB  - Over the past few years, studies of manometric techniques have improved our
      ability to accurately assess pharyngeal pressure events during swallowing. Solid
      state transducers, circumferentially recording transducers, and on-line computer
      interpretation allow quantitative measurements. Studies in normal subjects will
      permit better recognition of pathologic states.

PMID- 8269728
TI  - Manometric evaluation of the esophagus.

PMID- 8269727
TI  - The use of intraluminal manometry to assess upper esophageal sphincter function.
AB  - The UES is a striated muscular structure that exhibits substantial variation in
      tone in response to a wide variety of stimuli as well as during deglutition. It
      is an asymmetric structure subject to substantial axial movement. Hence the
      findings on UES manometry are highly dependent upon the manometry equipment used,
      positioning of this equipment in relation to the UES, and external stimuli. There
      is considerable intrasubject and intersubject variation in some parameters from
      UES pressure recordings. These factors must be taken into accout in the clinical
      use of UES manometry.

PMID- 8269729
TI  - The sphincter mechanism at the lower end of the esophagus: an overview.

PMID- 8269730
TI  - Electromyography and the study of oropharyngeal swallowing.

PMID- 8269731
TI  - Radiographic techniques and interpretation of abnormal swallowing in adult and
      elderly patients.
AB  - The radiologic evaluation of oropharyngeal dysfunction requires interpretation of
      observed morphodynamics and bolus movements. This can be facilitated if a
      simplified biomechanical approach is used to understand basic physiology. Oral
      stage activity can be described as a lingual delivery pump and pharyngeal stage
      activity as a glossopharyngeal propulsion pump. Bolus misdirection into the
      airway is more often due to oral rather than pharyngeal abnormalities and is
      frequently inconsistent with regard to timing and degree. The video-deglutition
      examination is still a relatively new diagnostic study and its purpose,
      indications, and criteria for patient selection should be clearly understood.

PMID- 8269733
TI  - Mechanical studies of the esophageal function.
AB  - The discussion centers on the use of mechanical principles, mathematical
      modeling, and concurrent manometric and videofluoroscopic data to study the
      esophageal function. Basic principles of mechanics indicate that intrabolus
      pressure must be distinguished from the direct contractile squeeze of the
      circular muscle on the manometric assembly. Because these two regions are
      mechanically distinct, pressure amplitude is not a proper indicator of the forces
      characterizing esophageal bolus transport. In the application of computer
      simulations to the transport of a fluid bolus through the aortic arch regions, it
      was discovered that separate contraction waves must exist in the upper and lower
      esophageal segments when bolus retention occurs. Through detailed analysis of
      enhanced concurrent manometric and videofluoroscopic data in human volunteers, we
      have found that a dual-wave characteristic across the transition zone is a normal
      reflection of the change in muscle types, each muscle type producing a separate
      contraction wave. In normal transport, these two contraction waves are properly
      coordinated spatially and temporally. However, during bolus retention, a mismatch
      in space and time between these two waves takes place. Analysis suggests that
      this mismatch is neurological rather than histological in origin, and occurs
      primarily within the lower smooth-muscle segment.

PMID- 8269732
TI  - The videoendoscopic swallowing study: an alternative and partner to the
      videofluoroscopic swallowing study.
AB  - A new, physical examination-based videoendoscopic method of evaluation can
      enhance considerably the understanding and efficiency of clinicians working with
      patients with swallowing difficulties. Using the fiberoptic nasolaryngoscope,
      evaluation of structure and function of palate, pharynx, and larynx, along with
      sensation of the laryngopharynx, is carried out. Next, patients' swallowing
      capabilities are assessed as they ingest various food consistencies. This method,
      formerly called videoendoscopic evaluation of dysphagia (VEED), but perhaps more
      appropriately termed videoendoscopic swallowing study (VESS) has particular value
      for patients who cannot undergo the videofluoroscopic swallowing study (VFSS)-
      for example, because they are bedfast--or those whose swallowing function is
      changing so rapidly (after a stroke or surgery) as to call for frequent
      reassessments. This technique is often useful during the initial consultation
      with new patients complaining of dysphagia, as a "stand alone" method of
      diagnosis and management. Less frequently, VESS findings, along with patient
      history, will indicate when VFSS should also be obtained. VESS will orient the
      examiner to the nature and severity of the problem even in this latter
      circumstance. In follow-up circumstances, VESS is generally more useful than the
      VFSS. Case presentations are utilized to illustrate the usefulness of VESS as
      compared to VFSS.

PMID- 8269734
TI  - [Patient education regarding intra- and postoperative blood transfusions-
      recommendations of the DKG].

PMID- 8269735
TI  - [Limits in medicine. Ethical and economic aspects].

PMID- 8269736
TI  - [The surgeon must also be a manager].

PMID- 8269737
TI  - [Preoperative patient education about transfusion risks--medico-legal
      considerations of a BGH decision].

PMID- 8269738
TI  - [Accidental injuries of the urogenital tract within the scope of visceral surgery
      interventions].

PMID- 8269739
TI  - [Visceral surgery techniques within the scope of urologic interventions].

PMID- 8269740
TI  - [Laparoscopic boundaries between urology and visceral surgery].

PMID- 8269742
TI  - [Ligation of the cystic duct--experience in 1,750 laparoscopic
      cholecystectomies].
AB  - Between 3/1990-3/1993 laparoscopic cholecystectomy was performed in 1750 patients
      in the mean age of 49.8 (7-83). In 48 patients (2.7%) the procedure had to be
      shifted to open surgery. The overall complication rate was 3.9%, the mortality
      0.11%. The PDS-clip Absolok 300 was regularly used for occluding the cystic duct
      and the cystic artery. Clip-associated complications were never observed. The
      induced duct occlusion proved save even against operative manipulation. But
      special characteristics of the clip and its application had to be considered.

PMID- 8269741
TI  - [Single hepatocellular carcinoma (phi < or = 5 cm) in liver cirrhosis. Early
      diagnosis and surgical removal].
AB  - 721 patients with liver cirrhosis were regularly screened by sonography and
      determination of alpha fetoprotein during a period of eleven years (1.1.1982
      1.1.1993). In 137 of them hepatocellular carcinoma (HCC) was diagnosed; 28
      (20.4%) had a unilocular HCC with a diameter up to 5 cm. Diagnosis was regularly
      verified by sonographic guided puncture, in rare cases by laparoscopy and biopsy.
      Beside a diameter of 5 cm the tumor should be localized at least 5 mm from the
      main structures in the hilus, and not in the centre of the liver; furthermore
      multilocular hepatocellular carcinomas and intra- and extrahepatic metastases
      were contraindications. Child-Pugh-classification should be A+B and urea
      synthesis rate at least 6 g per day. In 21 patients (75%) a portal hypertension
      was diagnosed; 19 (68%) had bled from esophageal varices; in case of one bleeding
      a therapeutic sclerotherapy and in case of recurrent variceal hemorrhage an
      elective shunt operation were performed. Surgical resection was carried out with
      controlled hypotension and temporary occlusion of the hepatoduodenal ligament.
      Tumor was removed by segmentectomy or bisegmentectomy and in rare cases by
      enucleation. There were 3 clinical deaths (10.7%); causes of death were liver
      failure and (2) sepsis (1). All patients could be followed up to January 1, 1993;
      there were 12 further deaths of liver failure, tumor recurrence or second tumor.
      13 patients are still living. Thus the live expectancy for one year was 80, for 5
      years 50 and for 10 years 30%. There is no doubt, that it is possible to detect
      hepatocellular carcinoma in patients with liver cirrhosis early by regular
      sonography and determination of alpha-fetoprotein.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8269743
TI  - [Laparoscopic cholecystectomy with the ultrasound dissector].
AB  - Due to tissue selectivity the ultrasonic dissector facilitates anatomical
      clearance even in difficult situations. Although of no advantage in routine
      laparoscopic cholecystectomies and even more time consuming, it seems to be of
      considerable value in difficult laparoscopic cholecystectomies and offers more
      safety for the patient.

PMID- 8269744
TI  - [Surgical therapy of myasthenia gravis and thymoma].
AB  - Between 1986 and 1992 eighteen patients underwent transsternal radical thymectomy
      at the Department of Surgery of the RWTH Aachen. Operation was indicated for
      myasthenia gravis (n = 14) or suspect of thymoma (n = 4). Patients with
      myasthenia were preoperatively classified according to Osserman and
      postoperatively with respect to their clinical status and drug dosages. Patients
      with thymoma were classified according to Masaoka. After a mean follow-up period
      of 43.6 months 76.9% of the patients with myasthenia demonstrated a significant
      improvement. All patients with thymoma were free of recurrence.

PMID- 8269745
TI  - [Patient-controlled analgesia (PCA) for postoperative pain relief. A prospective
      observational study for evaluating the technology in a ward routine].
AB  - Patient-controlled analgesia (PCA) is rarely used on surgical wards despite
      described advantages of this method as compared to conventional techniques.
      Uncertainties in patient selection and insufficient evaluation of this technique
      may explain these circumstances. The aim of our study was to evaluate PCA on
      general surgery and traumatology wards by means of standardized criteria for
      technology assessment (i.e. safety, practicability, benefit for patients and
      medical staff) and the efficacy of pain relief. In a prospective study we
      investigated 120 patients. In phase I, we performed analgesic therapy with
      tramadol/metamizol (50 ASA status I-IV patients). In phase II, piritramid had
      been applied to 70 ASA status I-II patients after an intermediate analysis of
      phase I. In 7% of the patients technical problems led to an early interruption
      even at the end of the study period. There were, however, no incidents which
      caused vital problems for the patients. A mean postoperative pain level of 55
      visual analogue scale points (0-100 point scale) was achieved with
      tramadol/metamizol. PCA was stopped in 16% of the patients due to the occurrence
      of nausea or vomiting and in two patients due to insufficient pain relief. The
      use of piritramid in phase II led to lower pain levels and no interruptions of
      PCA because of ineffectivity or nausea/vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269746
TI  - [Hereditary thrombophilia as a cause of recurrent transplant thromboses].
AB  - We report a case of hereditary protein S and protein C deficiency which are a
      rare defects of the anti-coagulation-system. Protein S is a vitamin K dependent
      glycoprotein that functions as a cofactor to activated Protein C in the
      inactivation of coagulation factors V and VIIIa. A deficiency of these proteins
      caused by a genetic defect increase the risk of recurrent thrombosis at a younger
      age. Acquired decreases in protein S and C concentration have been reported in
      connection with age, sex, pregnancy and with oral anticonception. The higher risk
      for thrombotic diseases of patients with thrombophilia requires a sufficient
      treatment and prophylaxis, e.g. with fresh frozen plasma or a protein C
      concentrate.

PMID- 8269747
TI  - [Experiences with the Stamm gastrostomy in children].
AB  - This paper is a retrospective analysis of 280 children, who were treated with a
      gastrostomy by the technique of Stamm in the Pediatric Surgical Clinic at Dr. v.
      Haunersches Kinderspital of the University of Munich from 1st January 1978 until
      31st December 1989. Points of interest were epidemiological data such as the age
      and the original illness of the patients and the duration of gastrostomy. In 229
      children the gastrostomy was performed within the first week of life. The most
      frequent indication was the diagnosis of an esophageal atresia in 80 cases. 94 of
      the patients had further malformations, in 30% as a syndrome. In 50% of all cases
      the gastrostomy could be removed within 40 days after operation, in further 40%
      between the 40. and 90. postoperative day and in the last 10% later. Heavy
      complications could be diagnosed in 2.9% without any mortality, easy
      complications in 10%.

PMID- 8269748
TI  - [Thoracoscopic operation of a tumor of the esophageal wall].
AB  - Improvements in video endoscopic technique opens a wide spreaded field of
      indications of thoracoscopic surgery especially in benign tumors of the
      esophagus. A 58-years old patient presented with dysphagia. Preoperatively a
      benign, intramural tumor of the esophagus wall was diagnosed. Enucleation of the
      tumor was performed by right videothoracoscopy. The use of thoracoscopic
      operative technique implies rapid disappearance of complaints and a reduced time
      of hospitalisation.

PMID- 8269749
TI  - [Richter's hernia. An unusual disease course and incidence in a personal patient
      sample].
AB  - Richter's hernia is a special type of incarcerated hernia with strangulation of
      only a part of the circumference of the bowel wall. Diagnosis may be delayed for
      the frequent absence of intestinal obstruction or the mild local signs especially
      in the femoral site. Untreated, there may be formation of an abscess without
      communication to the peritoneal cavity with secondary formation of an
      enterocutaneous fistula. We describe the history of a 87 years old patient with a
      femoral hernia and formation of an enterocutaneous fistula 9 months after
      incarceration. Discussion with review of the literature.

PMID- 8269750
TI  - [Laparoscopic operation of incarcerated obturator hernia with assisted intestinal
      resection].

PMID- 8269751
TI  - [Amelanotic melanoma of the rectum].
AB  - We report the very rare case of an amelanotic anorectal melanoma. Until now there
      are only three other well documented cases of that tumor-type reported in the
      literature. The course of disease is described from initial symptoms till 10
      months after discharge from hospital and suggestions for staging, therapy and
      follow-up are made.

PMID- 8269752
TI  - [Organic hyperinsulinism in advanced age].
AB  - Case report of a 87 years old women with symptomatic organic hyperinsulinism for
      30 years. After description of the clinical course following resection of the
      left pancreas, diagnostic and therapeutic procedures are discussed.

PMID- 8269753
TI  - [Management of gynecologic diseases with surgical pelviscopy].

PMID- 8269754
TI  - [Bone biopsy in detecting metabolic bone diseases].

PMID- 8269755
TI  - [Diagnosis and treatment of angina-like chest pain in 52 cases].
AB  - Esophageal investigation was performed successfully in 52 patients who were
      initially suspected of suffering from angina pectoris, but the pain was
      subsequently shown to be not of cardiac origin by radionuclide myocardiac
      perfusion and (or) coronary angiography in 74% of cases, and by EKG and poor
      response to anti-angina therapy in 26% of the cases. In 82.7% of the patients the
      diagnosis was gastroesophageal reflux disease (GERD), in 3.8% Nutcracker
      esophagus, and in 5.8% lower esophageal sphinctor hypertension. In the remaining
      7.7% the diagnosis was unknown. In 43 patients with GERD, gastroesophageal reflux
      (GER) investigation showed GER symptoms in 61.5%, reflux esophagitis was
      confirmed with endoscopy in 45.3%. Abnormal esophageal manometry was found in
      53.8%, positive provocative test in 42.9%, excessive radionuclide GER in 50%, and
      increased duration of hyperacidity in 57.1%. However, a combined study of the
      procedures mentioned above showed that the diagnosis was consistent with GERD in
      82.3% of the patients. Chest pain was completely relieved in 34% of the cases and
      significantly relieved in 50%. No response was ilicited in 16% of the cases after
      1-2 weeks of anti-reflux therapy. It is found that chest pain induced by GERD is
      very common, esophageal endoscopy and motor studies are helpful in the diagnosis
      of GERD and other esophageal motor diseases, and anti-reflux therapy is a
      reliable measure when a patient complains of unknown chest pain and GER symptoms.

PMID- 8269756
TI  - [An urease enzyme linked immunosorbent assay for detection of Helicobacter pylori
      infection].
AB  - A sensitive and specific serological diagnostic test for Helicobacter pylori
      infection has been developed and validated in 120 patients with dyspeptic
      symptoms undergoing endoscopy. This test is to use urease, a protein unique to H.
      pylori, as the basis for the enzyme linked immunosorbent assay (ELISA) that
      detects serum H. pylori urease antibodies. The ELISA mean optical density (OD) in
      H. pylori-positive group is higher than that in H. pylori-negative group (0.57 +/
      0.23 vs 0.24 +/- 0.15, P < 0.001), a cut-off 0.3 OD yields a sensitivity of 95%
      and a specificity of 93%. Serum absorption test showed that Escherichia coli,
      Klebsiella pneumonia, Proteus mirabilis, Yersinia enterocolotica, Pseudomonas
      aeruginosa cell lysate do not influence serum H. pylori urease antibody level,
      though they all have urease except E. coli. The result implied that H. pylori
      urease can be a good antigen to detect serum H. pylori antibody and it would be
      useful for epidemiological survey and routine diagnostic approach. Nearly half of
      the blood donors showed positive result with H. pylori urease antibody. It is
      suggested that H. pylori infection is quite common in the asymptomatic
      population.

PMID- 8269757
TI  - [Gastric emptying time with 99mTc-resin solid experiment meal].
AB  - Half gastric emptying time (GET1/2) was measured by using radionuclide gamma
      photography with 99mTc-resin solid experiment meal. The results were as follows:
      1. GET1/2 in the normal controls (10 cases) was 51.62 +/- 3.69 minutes. 2. GET1/2
      in mild chronic atrophic gastritis (CAG) patients was 51.68 +/- 9.20 Min, not
      significantly different with the normal controls (P > 0.05). GET1/2 in 15 cases
      with moderate and severe CAG was 70.39 +/- 14.86 Min, which was apparently longer
      than that in normal controls (P < 0.01). 3. There was no significant difference
      in GET1/2 between carcinoma of the gastric corpus, fundus and cardia (50.77 +/-
      2.73 Min) as well as the normal controls (P > 0.05). GET1/2 of the cancer of
      gastric antrum was 89.06 +/- 19.55 Min, being longer than that in normal controls
      (P < 0.01). 4. No obvious difference was observed between the GET1/2 of patients
      with corpus and fundus peptic ulcer (55.36 +/- 6.80 Min.) and the normal controls
      (P > 0.05). It was apparently longer in patients with antral peptic ulcer (76.62
      +/- 16.96 Min.) than in patients with ulcers of corpus, fundus and normal
      controls (P < 0.01). 5. GET1/2 in patients with duodenal ulcer (42.49 +/- 6.26
      Min.) was apparently shorter than those with gastric ulcer and normal controls.
      6. GET1/2 in diabetic patients was 70.01 +/- 29, 46 Min, it was obviously longer
      in those patients with autonomic nervous dysfunction (84.03 +/- 22.31 Min.) than
      that those without (34.14 +/- 7.90 Min.).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269758
TI  - [Ultrastructural study of the thymus in patients with myasthenia gravis].
AB  - The ultrastructure of the thymus gland from ten patients with myasthenia gravis
      was studied and compared with that from three normal subjects. Thymic substance
      in myasthenia gravis showed inflammatory reaction characterized by presence of
      neutrophils and macrophages, plasma cell infiltration, epithelial reticular cell
      hyperplasia, and new germinal center formation. In contrast lymphoblasts and
      plasma cells were not present and there was no new germinal center formation in
      the thymus of normal subjects. It is suggested that humoral immunity plays an
      important role in the pathogenesis of myasthenia gravis. The function of the
      myoid cells and the significance of the secretory granules in epithelial cells
      could only be defined by ultrastructural study.

PMID- 8269759
TI  - [Pulmonary lymphangiomyomatosis: report of a case].
AB  - A case of pulmonary lymphangiomyomatosis in a 28-year-old woman with dyspnea,
      hemoptysis, chylothorax and irregular menstruation as presenting symptoms was
      reported. Chest CT scan showed the presence of pleural effusion on right side and
      a honeycomb pattern throughout the lung parenchyma bilaterally. The diagnosis was
      confirmed histologically by transbronchial lung biopsy. Medroxyprogesterone was
      administered; improvement in arterial blood gas analysis and reduction of the
      amount of pleural effusion were noted after one month. The etiology, clinical
      manifestations, pathological characteristics and treatment of this disease were
      discussed.

PMID- 8269760
TI  - [A preliminary report on the prevalence of different types of hepatitis in adult
      patients with acute sporadic hepatitis in Beijing area].
AB  - In order to investigate the prevalence of different types of viral hepatitis in
      Beijing area, the markers of viral hepatitis A, B, C and E were detected on 72
      adult patients with acute viral hepatitis in the infectious diseases department
      of our hospital. The results showed that 26.4% of the cases had HAV infection,
      8.3% HBV infection, 18.1% HCV infection and 31.9% HEV infection. It is shown that
      the prevalence of HEV infection in Beijing area is high.

PMID- 8269761
TI  - [Research on the activity and quantity of natural killer cells and T lymphocytes
      in myelodysplastic syndrome patients].
AB  - 24 patients with myelodysplastic syndrome (MDS) were examined for the following
      items. T lymphocyte subsets of five subtypes of MDS examined with monoclonal
      antibody were less than that in normal controls. After incubation of peripheral
      blood lymphocytes with PHA at 37 degrees C with 5% carbon dioxide, the amount of
      HLA-DR positive cells and NKH1 positive cells were less than normal, NK cell
      activity was measured with cytotoxicity assay using 51 Cr labeled target K562
      cells, the results showed that NK activity in MDS was less than that in controls.
      As mentioned above, the results indicated that the activity and quantity of T
      lymphocytes and NK cells in MDS were abnormal.

PMID- 8269762
TI  - [Tumor necrosis factor alpha in IgA nephropathy].
AB  - Tumor necrosis factor alpha (TNF alpha) in serum and supernate of peripheral
      blood lymphocyte stimulated by PHA in 100 cases of IgA nephropathy (IgAN) was
      evaluated by means of ELISA with TNF alpha monoclone antibody (T5 & E6). The
      results show that TNF alpha content in serum and supernatant was significantly
      higher in IgAN than in control (P < 0.01), and was increased markedly in IgAN
      with sclerosis (P < 0.01). It suggests that TNF alpha play an important role in
      cellular immunity of IgA nephropathy.

PMID- 8269763
TI  - [The treatment of acute ischemic cerebrovascular diseases].

PMID- 8269764
TI  - [Sporadic encephalitis].

PMID- 8269765
TI  - [Relation between stroke and heart diseases].

PMID- 8269766
TI  - [Effect of elevated plasma norepinephrine on electrocardiographic changes in
      subarachnoid hemorrhage].
AB  - We compared electrocardiographic abnormalities and plasma norepinephrine
      concentration in 40 patients with subarachnoid hemorrhage within the first 24
      hours, at 72 hours, and after 1 week. In the 20 patients with high plasma
      norepinephrine concentrations within the first 24 hours, sinus tachycardia and
      negative T waves were more frequently seen than in the 20 patients with normal
      plasma norepinephrine concentrations. After 72 hours, only sinus tachycardia was
      found with increased frequency in the 26 patients with high plasma norepinephrine
      concentrations. Although 24 patients had high plasma norepinephrine
      concentrations after 1 week, we found no difference in the frequency of
      electrocardiographic abnormalities as compared with patients with normal plasma
      norepinephrine. QT prolongation, U waves, ST depression, and arrhythmias were
      found with similar frequency in patients with high and normal plasma
      norepinephrine concentrations. We conclude that, with the exception of sinus
      tachycardia and negative T waves, other electrocardiographic changes in patients
      with subarachnoid hemorrhage do not depend on elevated plasma norepinephrine
      concentrations.

PMID- 8269767
TI  - [Five cases of Campylobacter jejuni enteritis accompanied with Guillain-Barre
      syndrome].
AB  - 17 cases of Guillain-Barre syndrome (GBS) were admitted to The First Hospital of
      Beijing Medical University and Baoding Hospital from July, 1991 to October, 1992.
      Five patients had diarrhea before the onset of GBS and showed positive reaction
      for serum IgM antibodies to Campylobacter jejuni. They were considered to have
      Campylobacter jejuni enteritis as well. This incidence of Campylobacter jejuni
      enteritis in GBS patients was higher than in those with other neurological
      diseases and in normal controls. These five patients were all from countryside
      and had their onset in the summer and autumn. Moreover, four of them were below
      twenty-four years old. The epidemiological pattern was quite similar to that of
      Campylobacter jejuni enteritis in China. Our data showed the close association
      between GBS and Campylobacter jejuni enteritis and the possible mechanism was
      discussed.

PMID- 8269768
TI  - [Clinical characteristics and coronary angiographic findings of spontaneous
      angina].
AB  - The clinical characteristics and coronary angiographic findings in 50 patients
      with spontaneous angina (SA) were studied. Coronary angiography did not disclose
      any severe fixed narrowing in 7 patients with SA only; the episodes of SA in
      these patients is the result of subtotal occlusion of a major coronary artery
      induced by spasm. 43 patients with both SA and effort angina (EA) had more severe
      coronary obstructive lesions. In these patients, the localization of
      electrocardiographic ischemia during episodes of SA and EA were always identical,
      indicating that the episodes of SA are related to the coronary narrowing lesions.
      Our study showed that incidence of SA was highest with 90% stenosis of the
      ischemia related artery, suggesting that besides coronary spasm, physiological
      coronary vasoconstriction or increase of coronary vasomotor tone could play an
      important role in the production of SA. In addition, turbulent flow, stasis,
      platelet aggregation and transient thrombosis might be individually responsible
      for episodes of SA in patients with severe coronary stenosis.

PMID- 8269769
TI  - [Cardiac amyloidosis: an analysis of five cases].
AB  - Five patients with the diagnosis of cardiac amyloidosis established by autopsy
      and biopsy of noncardiac tissue were reported. All of the patients had cardiac
      dysfunction. Echocardiogram showed symmetrical thickness of left ventricle,
      increase of heart weight and reduction of left ventricular ejection fraction.
      Only two cases had "granular sparkling" on the ventricular wall. The clinical
      findings of cardiac amyloidosis are arrhythmias, conduction disturbances and
      intractable heart failure. Echocardiographic examination may reveal cardiac
      involvement and severity of pathological involvement and predict prognosis. The
      "granular sparkling" is not a specific feature for the diagnosis of cardiac
      amyloidosis. Biopsy of either noncardiac or cardiac tissue is required for
      correct diagnosis.

PMID- 8269770
TI  - [A clinical and basic study on the relationship between acute myocardial
      infarction and endothelin].
AB  - The level of plasma endothelin (ET) was studied in 40 cases with acute myocardial
      infarction (AMI) with radioimmunoassay. The results showed that plasma ET level
      reached its peak value (46.01 +/- 1.64 pg/ml) immediately after AMI attack and
      dropped down (39.37 +/- 0.47 pg/ml) on the first day; The value was still high
      (15.56 +/- 1.40 pg/ml) on the twenty-eight day: this was significant higher than
      that in control group (6.35 +/- 0.44 pg/ml, P < 0.001). It was found that height
      of plasma ET level was closely correlated with severity of myocardial damage and
      degree of cardiac insufficiency. In order to evaluate the pathogenic role of ET
      in AMI, the effect of ET-antiserum on myocardial infarction (MI) was investigated
      on infarct model produced by ligature of left anterior descending coronary artery
      in rats. The results showed that plasma ET levels elevated significantly in rats
      with MI (8.4 +/- 1.0, sham 3.1 +/- 0.2 pg/ml, P < 0.01) and ET-antiserum
      administration dramatically decreased plasma ET level 65% (P < 0.01), lowered
      plasma content of lipid peroxide 27% (P < 0.01) and reduced infarct size 48% (P <
      0.01). It is suggested that ET is an important factor which contributes to the
      pathogenesis of MI. Limb ischemia and reperfusion study was carried out in rats
      also. Metallothionein (MT) was found to antagonize markedly ET-induced
      vasoconstriction and lower the release of ET stimulated by angiotensin II in a
      dose-dependent manner. It is suggested that under certain pathological conditions
      MT may exert its injury--resistant and cell protective action.

PMID- 8269771
TI  - [The effects of sodium nitroprusside and almitrine bismesylate on blood gases,
      hemodynamics and oxygen delivery in patients with cor pulmonale].
AB  - The effects of sodium nitroprusside and almitrine bismesylate on blood gases,
      hemodynamics and oxygen delivery were respectively studied in twenty-one and
      eighteen patients with cor pulmonale. The treatment of sodium nitroprusside
      resulted in significant decrease in pulmonary artery pressure. Although
      physiological shunt was increased (from 12.6 +/- 10.5 to 20.1 +/- 10.9%, P <
      0.01) and arterial oxygen tension was decreased (from 12.6 +/- 4.0 to 9.9 +/- 2.5
      kPa, P < 0.01) in patients undergoing mechanical ventilation, cardiac index (from
      44.8 +/- 10.5 to 53.3 +/- 12.8 ml.s-1/m-2, P < 0.05) and oxygen delivery index
      (from 7.8 +/- 1.7 to 9.2 +/- 2.3 ml.s-1/m-2, P < 0.05) were improved. After
      treatment with almitrine bismesylate, improvement of arterial oxygen tension was
      observed in patients with spontaneous breathing (from 6.7 +/- 0.6 to 7.8 +/- 0.6
      kPa, P < 0.05) and undergoing mechanical ventilation (from 10.9 +/- 1.9 to 13.4
      +/- 2.5 kPa, P < 0.01), but increment of mean pulmonary artery pressure (from 3.8
      to 0.5 and 3.1 +/- 0.8 to 6.3 +/- 0.7 and 3.6 +/- 0.9 kPa, respectively, P <
      0.01) was noted.

PMID- 8269772
TI  - [Complications of percutaneous renal biopsy: an analysis of 1000 consecutive
      biopsies].
AB  - The complications of percutaneous renal biopsies in 1000 cases are analysed in
      this paper. Because the modern techniques for biopsy localization and operation
      were used, both accidental puncture of other organs and infection were avoided.
      However, the hemorrhage of renal wound was still a predominate complication.
      Gross hematuria developed in 7.4% of biopsies, perirenal hematomas 4.4% of
      biopsies, and serious renal bleeding complications, including arteriovenous
      fistula, requiring transfusion of more than 1000 ml of blood were detected in
      0.6% of biopsies. In this paper the manifestations, diagnosis and treatment for
      every renal bleeding complication are discussed. It is emphasized that renal
      arteriography should be done for the patients with persistent or recurrent renal
      hemorrhage, and that selective arterial embolization by using self-blood
      coagulative pieces should be considered before deciding surgical correction of
      these serious bleeding complications.

PMID- 8269773
TI  - [Effects of alpha-ketoacids therapy on protein metabolism and secondary
      hyperparathyroidism in predialysis patients].
AB  - The effects of alpha-ketoacids (alpha-KA) on azotemia, plasma amino acids
      concentrations, nitrogen balance, serum Ca, PO4 and iPTH levels in 22 predialysis
      patients were investigated. The results showed that BUN and serum phosphate
      levels decreased significantly, plasma essential amino acids levels, nitrogen
      balance and serum calcium levels were improved after 6-8 weeks of alpha-KA
      therapy. The serum iPTH levels were reduced markedly three months after alpha-KA
      treatment and maintained lower ten months later.

PMID- 8269774
TI  - [The common causes and differential diagnosis of malignant jaundice].
AB  - To investigate the common causes and differential diagnosis of malignant
      jaundice, we reviewed 903 cases with obstructive jaundice in PUMC hospital in
      recent 16 years. 383 of them were malignant jaundice (42.4%). The most common
      origin of malignant jaundice was carcinoma of the pancreatic head with 198
      patients (51.7%), and carcinoma of the ampulla Vater with 94 cases (24.5%) and
      carcinoma of the extrahepatic bile duct with 71 cases (5.2%). The clinical
      symptoms and signs were not much helpful to the differentiation of malignant
      jaundice. No specific early signs were found to the malignant jaundice, but most
      of the patients felt epigastric distension and distress, anorexia, loss of body
      weight and fatigue before jaundice appeared. More than one third patients had
      discontinuous fever. The imaging investigation had decisive roles in the
      diagnosis and differential diagnosis of the malignant jaundice. The positive rate
      of diagnosis in sonography was 95.5%, but the correct rate only 85.0% (P < 0.05).
      We regard that sonography might be the first imaging examination for the
      malignant jaundice and clue for further investigation. ERCP can clearly reveal
      the papilla, biliary and pancreatic ducts with high positive rate (97.7%) and
      correct rate (95.1%). PTC was only used in those patients who had the
      contraindications to ERCP or the cannulation of ERCP was not successful. The
      positive rate of PTC was 95.8% in the cases with extrahepatic cholangiocarcinoma.
      The combination of ERCP and PTC could determine the position and extent of
      extrahepatic cholangiocarcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269775
TI  - [A report on therapy of interferon-A2b in patients with acute hepatitis C].
AB  - Sixteen patients with acute hepatitis C having a duration of illness more than
      three months without recovery were randomly assigned to treatment with interferon
      (IFN). 8 patients received 3 million units a day during the first week and 3
      million units every other day for the following 11 weeks. Another 8 patients were
      given 3 million units every other day for 12 weeks. An additional 16 patients
      were chosen as controls. The effect of IFN therapy was 93.8% in the treated group
      and only 12.5% in the control group (P < 0.005). Among 11 patients who completed
      the course of therapy, only one had a recurrence in a follow-up of 18-86 weeks,
      while 13 of the 14 patients in the control group showed persistent liver damage.
      It is concluded that therapy with IFN can reduce the risk of chronic infection in
      patients with acute HCV infection.

PMID- 8269776
TI  - [Superantigens and autoimmunity].

PMID- 8269777
TI  - [The treatment of rheumatoid arthritis].

PMID- 8269778
TI  - [Nonsteroidal antiinflammatory drugs and duodenal ulceration].

PMID- 8269779
TI  - [Epidemiological studies on primary Sjogren's syndrome].
AB  - 2,066 adult people of a Beijing suburb village were surveyed for primary
      Sjogren's syndrome, using questionnaire and serological tests in each case as the
      primary screening tool. 16 cases were discovered by Copenhagen criteria
      indicating a prevalence rate of 0.77% and 7 cases with a prevalence rate of 0.33%
      by Fox criteria. Similar study was done in 100 non-connective tissue diseases in
      patients. 4 cases were discovered by Copenhagen criteria and one case by Fox
      criteria. In 126 definite cases of primary Sjogren's syndrome, the longest time
      interval between first onset of symptoms and firm establishment of diagnosis was
      20 years with an average of 7.8 years indicating most cases were wrongly
      diagnosed or highly neglected.

PMID- 8269780
TI  - [A study of anti-D'E polypeptide in the diagnosis of mixed connective tissue
      disease].
AB  - By using immunoblotting technique (IBT) and salt extracts of rabbit thymus powder
      as antigen, we detected autoantibodies against polypeptides of extractable
      nuclear antigen (ENA) in 358 patients with different rheumatic diseases. It was
      found that antibodies against polypeptides with molecular weights of 13,900
      dalton (designated as D') and 11,500 dalton (designated as E) could be detected
      only in mixed connective tissue disease (MCTD) with a positive rate of 19.1%.
      These antibodies were termed collectively as anti-D'E polypeptide in this paper
      and shown to have high specificity for the diagnosis of MCTD (P < 0.001).

PMID- 8269781
TI  - [Serum soluble interleukin 2 receptor levels in patients with diffuse connective
      tissue diseases].
AB  - Soluble interleukin 2 receptor (SIL-2R) levels in serum appear to reflect the
      status of lymphocytic activation and proliferation. We examined the levels of
      serum SIL-2R in 65 patients with diffuse connective tissue diseases by using
      ELISA method. The mean levels of serum SIL-2R were respectively 0.46 U/L, 0.53
      U/L, 0.46 U/L in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA),
      and dermatomyositis during disease activity and were significantly higher than
      those in healthy controls (0.25 U/L). The levels of serum SIL-2R were 0.62 U/L
      and 0.60 U/L respectively in a patient with mixed connective tissue disease and a
      patient with systemic sclerosis. The levels of SIL-2R were respectively 0.24 U/L
      and 0.29 U/L in SLE and RA patients during clinical remission, being
      significantly lower than during disease activity. SLE patients with high SIL-2R
      levels were associated with high levels of 125I-DNA rate and erythrocyte
      sedimentation rate and lower levels of C3 complement components. The measurement
      of SIL-2R levels may be an useful indicator for monitoring disease activity in
      SLE and RA patients. Moreover it is a noninvasive method.

PMID- 8269782
TI  - [Experimental method and clinical significance of hidden rheumatoid factors].
AB  - Hidden rheumatoid factor (HRF) was detected in rheumatoid arthritis (RA) serum
      with ELISA after separation and dissociation of immune complex (IC). It was found
      that 60% of the patients with active RA has positive latex fixation test, whereas
      96% of them has been demonstrated to have IgM hidden rheumatoid factor (HIgMRF)
      and 70% of them IgG hidden rheumatoid factor (HIgGRF). When the disease was
      controlled, HIgMRF and HIgGRF was found in 24% and 12% respectively. The
      difference was significant with P < 0.01. Our results show that the presence of
      HRF in RA patients is related with the activity of the disease, but not with
      duration of disease, sex and age.

PMID- 8269783
TI  - [Seronegative synovitis syndrome].
AB  - 3 cases of seronegative synovitis syndrome were reported. Two elderly women and
      one man presented with symmetrical polysynovitis of acute onset involving most of
      their appendicular joints and flexor digitorum tendons associated with pitting
      edema of the dorsum of both hands and both feet. Rheumatoid factor was absent
      from serum samples in all and no radiologically evident erosions developed. All
      the three patients had a benign course and the disease resolved completely within
      2-18 months after the onset. None had deformities, erosions and/or relapse after
      being followed for 22-34 months. Literatures on this syndrome were reviewed.

PMID- 8269784
TI  - [Study on omeprazole 20 mg twice weekly in prevention of duodenal ulcer relapse].
AB  - The aim of this study is to propose a regimen of omeprazole 20 mg twice weekly
      for the prevention of duodenal ulcer (DU) relapse. 257 endoscopically verified DU
      patients entered this study. They were divided into four groups: (1) Group A, 68
      patients stopped treatment after healing of DU during treatment of cimetidine 800
      mg at night. (2) Group B, 72 patients healed DU after treatment of omeprazole 20
      daily. Then anti-ulcer drug was withdrawn. (3) Group C, after healing of DU, 54
      patients received a maintenance dosage of cimetidine 400 at night for up to 1
      year. (4) Group D, after healing of DU, 63 patients received omeprazole 20 mg
      twice weekly (every Monday and Thursday) for up to 1 year. All the patients were
      followed in out-patients department for assessment of symptomatic response and
      side effect. Endoscopic examination were performed in those patients when any
      symptom related to the upper gastrointestinal tract appeared. The cumulative
      recurrence rates of Group A to Group D at 6 months were 44.1%, 23.6%, 22.2% and
      4.8%, and that at 12 months were 76.5%, 36.1%, 27.8% and 6.3% respectively. The
      relapse rate of patients with omeprazole 20 mg twice a week was significantly
      lower than that of other groups at either 6 or 12 months. In patients with
      maintenance therapy of cimetidine, DU recurred more rapidly among smokers than
      nonsmokers, but there is no significant difference between smokers and nonsmokers
      receiving maintenance therapy of omeprazole.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269785
TI  - [The effect of low dose aspirin on the platelet function in patients with acute
      myocardial infarction].
AB  - To assess the appropriate dose of aspirin in the treatment of patients with acute
      myocardial infarction (AMI), 60 cases of AMI were randomized into 2 groups, 30
      cases each; one with conventional therapy, another with conventional therapy
      combined with daily oral aspirin 100mg. The second group was further divided into
      subgroup I with serum peak CK < 1000 U/L and subgroup II with serum peak CK >
      1000U/L. The parameters of platelet function including plasma TXB2, TXB2/6-keto
      PGF1 alpha, platelet aggregation induced by 5-HT and epinephrine were studied on
      different days for 3 weeks. The results revealed that there was a successful
      inhibition of platelet function as assessed by significant decrease of plasma
      TXB2 and TXB2/6-keto-PGF1 alpha ratio and inhibition of platelet aggregation in
      the subgroup I, but little effect on subgroup II. It is shown that in the
      treatment of AMI, a daily dose of 100mg of aspirin is insufficient for severe
      cases, and according to the observation in ISIS-2 study, a daily dose of aspirin
      around 160mg may be appropriate.

PMID- 8269786
TI  - [The effect of captopril on hemodynamics in patients of chronic obstructive
      pulmonary disease with pulmonary hypertension].
AB  - One of the main causes of pulmonary hypertension in chronic obstructive pulmonary
      disease (COPD) is considered to be hypoxic pulmonary vasoconstriction, which may
      partly be mediated by angiotensin II. Ten patients with COPD were administered
      with captopril (25mg sublingually). Hemodynamics blood gases renin activity
      inducing angiotensin II and angiotension converting enzyme (ACE) and TXB2/6
      ketone-PGF1 alpha were studied through Swan-Ganz catheter before and after
      administration of the drug. Captopril reduced mean pulmonary artery pressure and
      pulmonary vascular resistance by 22% and 30% respectively. Levels of ACE
      angiotension II and TXB2/6-ketone-PGF1 alpha were reduced. There was no
      significant change in blood gases. Heart rate and systemic arterial pressure did
      not change significantly. These results suggest that captopril is of value in
      reducing pulmonary artery pressure and pulmonary vascular resistance.

PMID- 8269787
TI  - [Detection and significance of HBV antigen in gallbladder tissue].
AB  - In order to know whether HBV antigen exists in extrahepatic tissue, we detected
      HBV antigen in liver and gallbladder tissue obtained from 31 cases with HBV
      chronic liver disease (17 active cirrhosis, 14 chronic hepatitis) by using
      polyclonal antibody and ABC method. All cases were diagnosed by biopsy (n = 12)
      or autopsy (n = 19), 25 were males and 6 females, the average age was 45.6 years.
      The results showed that in the liver tissue 30 cases were (96.77%) HBsAg positive
      and 15 cases (48.39%) HBcAg positive. In the gallbladder tissue 18 cases (58.06%)
      were HBsAg positive and 8 cases (25.81%) HBcAg positive. Although 26 cases had
      pathological changes in the gallbladder, the changes had no relation with the
      existence of HBV antigen. Their symptoms and signs were also not related with the
      existence of HBV antigen in the gallbladder. Among the 31 cases, 19 died. The
      cause of death was severe hepatic complication, but not the pathological change
      of the gallbladder. The results suggest that pathogenesis of HBV in extrahepatic
      tissue needs to be elucidated.

PMID- 8269788
TI  - [Effects of sex hormones on plasma lipoproteins in middle older age non-diabetes,
      diabetes and coronary heart disease].
AB  - We has observed the effects of sex hormones on plasma lipoproteins by analysing
      165 patients of non-diabetes mellitus (NDM), diabetes mellitus (DM) and coronary
      heart disease (CHD) in the elder than 45 years. Of these subjects, NDM were 54,
      DM 47, CHD 48 and DM with CHD 16. The result statistically showed that is a
      significant difference in high density lipoprotein cholesterol (HDL-C) and
      Apolipoprotein A1 (Apo-A1) between male and female subjects in NDM group and
      general population (P = 0.0001, 0.003 and P = 0.009, 0.002 respectively), but
      this statistically significant difference could not be observed between male and
      female patients in groups of DM, CHD and DM with CHD. After adjusting multiple
      factors of age, body mass index (BMI), estradiol (E2), fasting plasma insulin
      (FINS), fasting blood glucose (FBS) by the stepwise procedure analysis, the
      levels of HDL-C and Apo-A1 have significantly negative association with the level
      of testosterone (T) (P = 0.0012 and 0.0040), however, have no association with
      E2. Total cholesterol (TC) and triglyceride (TG) have no association with T and
      E2. The result suggests that T should be an independent risk factor which reduces
      HDL-C level.

PMID- 8269789
TI  - Prevalence of microalbuminuria in older-onset diabetes.
AB  - OBJECTIVE: To examine the prevalence of microalbuminuria and the relationships of
      microalbuminuria to blood pressure and other risk factors. RESEARCH DESIGN AND
      METHODS: Individuals diagnosed with diabetes at > or = 30 yr of age either taking
      insulin (n = 435) or not taking insulin (n = 363), who were participants in the
      population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy, were
      examined during 1984-1986. Random urine samples were collected and an
      agglutination inhibition test was used to determine the presence of
      microalbuminuria, which is defined as > or = 0.03 g/L but < 0.3 g/L. RESULTS: The
      frequency of microalbuminuria was 29.2% in those individuals taking insulin and
      22.0% in those not taking insulin. Microalbuminuria was significantly associated
      with the male sex, older age, higher systolic blood pressure, higher GHb, use of
      insulin, higher recent alcohol consumption, and a history of cardiovascular
      disease. CONCLUSIONS: These findings suggest a relationship between controllable
      risk factors, blood pressure and GHb, and microalbuminuria in older-onset
      diabetic individuals.

PMID- 8269790
TI  - Risk factors for the development of type II diabetes among men enrolled in the
      usual care group of the Multiple Risk Factor Intervention Trial.
AB  - OBJECTIVE: To study the association between selected risk factors and the
      subsequent incidence of type II diabetes over a 5-yr period. RESEARCH DESIGN AND
      METHODS: Between 1973 and 1976, a cohort of men from 22 clinical centers
      throughout the U.S. enrolled in the Usual Care group of the Multiple Risk Factor
      Intervention Trial. The men (5420 white, 428 black, 56 Asian, 70 Hispanic, and 26
      other) were nondiabetic at baseline, were in the upper 15% of risk for coronary
      heart disease, and had at least two annual follow-up visits for fasting glucose
      measurements. The average age was 46 yr and average body mass index was 27.6
      kg/m2. Incidence of diabetes was defined as use of insulin or hypoglycemic
      agents, fasting glucose > or = 140 mg/dl on two consecutive annual visits, or
      fasting glucose > or = 140 mg/dl followed the next year by insulin or
      hypoglycemic use. Observations were taken annually over a 5-yr period. RESULTS:
      Cumulative incidence of diabetes over 5 yr was 4.1%, with 247 incident cases.
      Development of diabetes was directly associated with race (blacks higher than non
      blacks), reported parental history of diabetes, and with baseline levels of body
      mass index, fasting glucose, and glucose 1 h after a 75-g oral glucose load.
      These associations were statistically significant in both univariate and
      multivariate models. A significant interaction was observed between race and
      reported parental history of diabetes in development of diabetes, particularly
      within black men who reported a parental history. These individuals had higher
      than expected rates of diabetes development. CONCLUSIONS: The data from men in
      the Usual Care group enrolled in the Multiple Risk Factor Intervention Trial
      confirm previous findings regarding the associations between the development of
      diabetes and baseline glucose levels, obesity, race, and parental history of
      diabetes. The identification of these risk factors provides very powerful tools
      to identify individuals at high risk of diabetes mellitus who may be amenable to
      intervention, thereby reducing their risk of developing the disease and its
      complications.

PMID- 8269791
TI  - Familial hyperproinsulinemia associated with NIDDM. A case study.
AB  - OBJECTIVE: To report studies on an elderly patient with moderate NIDDM associated
      with marked fasting hyperinsulinemia. RESEARCH DESIGN AND METHODS: The propositus
      and several family members were studied by a combination of clinical,
      biochemical, and molecular genetic approaches to define the underlying genetic
      defect. RESULTS: Fasting levels of contrainsulin hormones were normal, and
      resistance to exogenous insulin was absent. Gel filtration and reverse-phase high
      performance liquid chromatography revealed elevated amounts of a structurally
      abnormal proinsulin intermediate (AC proinsulin). A study of the family of the
      propositus showed the same abnormality in 4 of 5 members in 3 successive
      generations. Genetic analysis revealed a point mutation affecting residue 65 of
      human proinsulin (Arg-->His) in one allele of the insulin gene in the propositus,
      a defect similar to that described previously in 3 other apparently unrelated
      lineages. CONCLUSIONS: This family exhibits a clear-cut relationship between
      increasing age and metabolic decompensation in all the hyperproinsulinemic
      members, suggesting that (inherited) metabolic stress and age both contribute to
      development of diabetes mellitus.

PMID- 8269792
TI  - Improved insulin action and glycemic control after long-term angiotensin
      converting enzyme inhibition in subjects with arterial hypertension and type II
      diabetes.
AB  - OBJECTIVE: To determine the long-term effects of the angiotensin-converting
      enzyme inhibitor captopril on insulin sensitivity in subjects with type II
      diabetes and arterial hypertension. The chronic effects of angiotensin-converting
      enzyme inhibition on insulin-sensitive individuals are presently controversial.
      RESEARCH DESIGN AND METHODS: Sixteen subjects, with type II diabetes (on diet
      and/or diet plus oral hypoglycemic agents) and arterial hypertension, were
      studied. During a 1-mo run-in period no antihypertensive drugs were administered,
      but oral hypoglycemic agents were continued in subjects already in therapy. The
      subjects were then randomly assigned to two 3-mo treatment periods, with either
      captopril or placebo (single blind, cross-over design). At the end of each
      treatment period, insulin sensitivity was assessed by means of a euglycemic
      hyperinsulinemic clamp (2 sequential steps, 2-h each, insulin infusion 0.25 and 1
      mU.kg-1.min-1, steps 1 and 2, respectively), combined with infusion of [3
      3H]glucose (for calculation of hepatic glucose output and peripheral glucose
      utilization, rates of glucose disappearance), and indirect calorimetry (for
      calculation of glucose oxidation, nonoxidative glucose metabolism, and lipid
      oxidation). The percentage of HbA1c was measured to assess long-term glycemic
      control. RESULTS: Comparing data at the end of placebo and captopril treatment,
      captopril resulted in: lower blood pressure (systolic 154 +/- 2 vs. 163 +/- 3
      mmHg and diastolic 93 +/- 2 vs. 101 +/- 2 mmHg); greater insulin sensitivity in
      hyperglycemic conditions (total amount of insulin infused and time of insulin
      infusion required to reach euglycemia, 1.73 +/- 0.54 vs. 2.08 +/- 0.60 U and 58
      +/- 8 vs. 70 +/- 11 min, captopril and placebo, respectively, P < 0.05); greater
      insulin sensitivity in euglycemic conditions at liver level (hepatic glucose
      output 4.11 +/- 0.55 vs. 5.2 +/- 0.4 mumol.kg-1.min-1, step 1 of the clamp),
      muscle level (rates of glucose disappearance 26.1 +/- 2.3 vs. 23.8 +/- 2.1
      mumol.kg-1.min-1 step 2 of the clamp), primarily attributable to approximately
      29% increase in nonoxidative glucose metabolism, and adipose tissue level (plasma
      free fatty acid 0.185 +/- 0.03 vs. 0.24 +/- 0.02 mM and lipid oxidation 1.9 +/-
      0.3 vs. 2.21 +/- 0.04 mumol.kg-1.min-1 in step 1); and lower HbA1c (6.7 +/- 0.2
      vs. 7.3 +/- 0.2%, P < 0.05). CONCLUSIONS: Long-term captopril administration in
      type II diabetic subjects improves insulin sensitivity in the postprandial state,
      not in the fasting state, and improves glycemic control.

PMID- 8269793
TI  - Comparison of diets of diabetic and nondiabetic women.
AB  - OBJECTIVE: To assess the dietary habits of diabetic women. RESEARCH DESIGN AND
      METHODS: Participants in the Nurses Health Study, a cohort of 121,700 registered
      female nurses, were followed since 1976. We compared the usual dietary intakes of
      women who had been diagnosed with diabetes mellitus by 1980 and age-matched
      nondiabetic control women; diets of these women were assessed in 1980 and 1984 by
      a semiquantitative food frequency questionnaire. The study examined 162 IDDM
      women and 738 NIDDM women. Similar comparisons were made for 429 women who
      developed NIDDM between 1980 and 1984. RESULTS: Although differences were small,
      women with IDDM in 1984 and women with NIDDM in 1980 and 1984 consumed less
      energy from carbohydrates, especially from sucrose, and more energy from protein
      and fat than did control women. Similar results were also found in 1984 for the
      429 women who developed NIDDM between 1980 and 1984. In 1980, energy from
      nonsucrose carbohydrate was slightly higher in both IDDM and NIDDM women than in
      the control women. However, in 1984, using a dietary questionnaire designed to
      assess more complete dietary intake, less consistent results were obtained.
      Diabetic women tended to avoid desserts and sweets, sugar-containing beverages,
      and alcoholic beverages but consumed more meat and meat products. Intakes of
      foods high in complex carbohydrates (e.g., bread, rice, pasta, and potatoes) were
      similar between diabetic and control women. CONCLUSIONS: The results suggest that
      these diabetic women did not consume the high-carbohydrate, low-fat diets that
      the American Diabetes Association has been recommending over the past decade.

PMID- 8269794
TI  - Effectiveness of glucose monitoring systems modified for the visually impaired.
AB  - OBJECTIVE: To compare three glucose meters modified for use by individuals with
      diabetes and visual impairment regarding accuracy, precision, and clinical
      reliability. RESEARCH DESIGN AND METHODS: Ten subjects with diabetes and visual
      impairment performed self-monitoring of blood glucose using each of the three
      commercially available blood glucose meters modified for visually impaired users
      (the AccuChek Freedom [Boehringer Mannheim, Indianapolis, IN], the Diascan SVM
      [Home Diagnostics, Eatontown, NJ], and the One Touch [Lifescan, Milpitas, CA]).
      The meters were independently evaluated by a laboratory technologist for
      precision and accuracy determinations. RESULTS: Only two meters were acceptable
      with regard to laboratory precision (coefficient of variation < 10%)--the
      Accuchek and the One Touch. The Accuchek and the One Touch did not differ
      significantly with regard to laboratory estimates of accuracy. A great
      discrepancy of the clinical reliability results was observed between these two
      meters. The Accuchek maintained a high degree of reliability (y = 0.99X + 0.44, r
      = 0.97, P = 0.001). The visually impaired subjects were unable to perform
      reliable testing using the One Touch system because of a lack of appropriate
      tactile landmarks and auditory signals. CONCLUSIONS: In addition to laboratory
      assessments of glucose meters, monitoring systems designed for the visually
      impaired must include adequate tactile and audible feedback features to allow for
      the acquisition and placement of appropriate blood samples.

PMID- 8269795
TI  - Serum insulin and glucose concentrations in people at risk for type II diabetes.
      A comparative study of African Americans and Nigerians.
AB  - OBJECTIVE: To examine the phases of acute insulin release and glucose homeostasis
      in people of African descent with and without a positive family history of type
      II diabetes who reside in geographically diverse environments. The prevalence of
      type II diabetes in people of African descent varies considerably depending on
      the country of habitat. Family history is recognized as an important risk factor
      for the development of the disease. RESEARCH DESIGN AND METHODS: We studied serum
      glucose and insulin concentrations--before and after intravenous glucose
      challenge--in glucose-tolerant, first-degree relatives of African-American (n =
      18) and Nigerian (n = 20) type II diabetic patients and their respective healthy
      control subjects (African American, n = 9; Nigerian, n = 18) living in their
      native countries. The acute first- (t = 0-5 min) and second-phase (t = 10-60 min)
      insulin releases were calculated as the sum of incremental insulin responses to
      the intravenous glucose stimulation. RESULTS: Mean serum glucose levels and
      glucose decay constant (KG) were not different in the African Americans and
      Nigerians. Fasting serum insulin in the African-American relatives was
      significantly greater than the Nigerian relatives (16.0 +/- 3.0 vs. 5.8 +/- 1.7
      mU/L, P < 0.05). In contrast, FSI levels in the African-American control subjects
      were similar to Nigerian control subjects (6.3 +/- 1.4 vs. 4.5 +/- 1.8 mU/L).
      Acute first- and second-phase insulin levels were 2-3 times (P < 0.01) greater in
      African Americans than Nigerians, irrespective of family history of diabetes.
      Comparing the African-American relatives with healthy control subjects, we found
      significantly (P < 0.05) higher FSI in the relatives; whereas the acute first-
      (272 +/- 44 vs. 222 +/- 55 mU/L) and second-phase (388 +/- 61 vs. 235 +/- 53
      mU/L) serum insulin release tended to be greater, but not significantly different
      in the relatives. In contrast, the acute first (101 +/- 15 vs. 120 +/- 20 mU/L)
      and second phase (88 +/- 14 vs. 111 +/- 17 mU/l) of insulin release were slightly
      lower, but not significantly different, in the Nigerian relatives versus the
      Nigerian healthy control subjects. In a subgroup of nonobese African-American (n
      = 11) and Nigerian (n = 11) relatives, and African-American (n = 8) and Nigerian
      (n = 7) healthy control subjects with a body mass index < 30 kg/m2, the mean
      fasting and post-stimulation serum glucose were not different. However, serum
      insulin concentrations in the African Americans were significantly different from
      those of the Nigerians. The pattern of insulin responses in the nonobese subjects
      was similar to those of the respective African-American and Nigerian groups.
      CONCLUSIONS: Our preliminary study demonstrates greater serum insulin responses
      and, perhaps, insulin resistance in glucose-tolerant African Americans than in
      their Nigerian counterparts, irrespective of family history of diabetes and
      obesity. We conclude that the antecedent lesions leading to the development of
      type II diabetes may be different in the first-degree relatives of African
      American and Nigerian diabetic patients.

PMID- 8269796
TI  - Predictors of microalbuminuria in individuals with IDDM. Pittsburgh Epidemiology
      of Diabetes Complications Study.
AB  - OBJECTIVE: To examine the relationships between microalbuminuria and the
      development of overt diabetic nephrology, elevated blood pressure, and a more
      atherogenic lipid profile; and to identify risk factors for the development of
      microalbuminuria in individuals with IDDM. Microalbuminuria has been associated
      with the subsequent development of overt diabetic nephropathy in individuals with
      IDDM. It is associated with elevated blood pressure and a more atherogenic lipid
      profile, but the temporal relationship between the development of
      microalbuminuria and the changes in these factors is unclear. RESEARCH DESIGN AND
      METHODS: Baseline characteristics were examined in 256 individuals with IDDM who
      had normal albumin excretion (urinary AER < or = 20 micrograms/min in > or = 2
      timed urine collections) and were re-examined 2 yr later. RESULTS: At follow-up,
      24 had developed microalbuminuria (AER 20-200 micrograms/min in > or = 2 timed
      urine collections) and 1 had developed overt nephropathy (AER > 200
      micrograms/min). Overall, the significant independent predictors of
      microalbuminuria were HbA1 (P < 0.001), low-density lipoprotein (P < 0.01),
      duration of IDDM (P < 0.05), and systolic blood pressure (P = 0.05). Sex-specific
      analyses showed HbA1, age, and baseline AER were particularly important for men;
      whereas, for women, the main predictors were duration of IDDM and triglycerides.
      Duration-specific analyses showed that HbA1 was an important predictor both for
      individuals with < and > 20-yr duration. Low-density lipoprotein cholesterol was
      more important for subjects with shorter durations; whereas triglycerides were
      important for those with longer durations. CONCLUSIONS: These results suggest
      that glycemic control, age or duration of IDDM, disturbed lipids, and possibly
      elevated blood pressure all may contribute to the development of
      microalbuminuria; and, further, that the adverse cardiovascular risk profile seen
      in individuals with overt nephropathy may begin to develop even before the
      detection of microalbuminuria.

PMID- 8269797
TI  - Does crossing the legs decrease arterial pressure in diabetic patients with
      peripheral vascular disease?
AB  - OBJECTIVE: To evaluate the effect of crossing the legs at the knee and the ankle
      on peripheral arterial pressures. RESEARCH DESIGN AND METHODS: A prospective
      study of 6 diabetic patients with known peripheral vascular disease and 5
      nondiabetic control subjects without peripheral vascular disease was conducted.
      Peripheral arterial pressures were taken at the ankle and at the great toe before
      and after crossing the legs at the knees and ankles. Comparisons were made of
      measurements obtained in the supine and sitting positions. All crossed leg
      measurements were taken in the sitting position. RESULTS: Ankle arm indexes and
      digital arm indexes pressures taken in the sitting position were equal to or
      higher than supine pressures, with the exception of one subject, GB. In this
      patient, ankle arm indexes and digital arm indexes on the right extremity were
      lower in the sitting position, but increased with the legs crossed at the knees
      and ankles compared with the uncrossed sitting position. In all patients, lower
      extremity pressures that decreased slightly with crossing the legs remained
      higher than pressures obtained in the supine position. Statistical analyses
      showed no significant differences. Wave forms did not change even when there was
      a slight decrease in ankle arm indexes or digital arm indexes. Control subjects
      without peripheral vascular disease showed no change in pressures with crossing
      the legs. CONCLUSIONS: Crossing the legs at the knees and ankles does not result
      in a significant decrease in peripheral arterial pressures in diabetic patients
      with peripheral vascular disease.

PMID- 8269798
TI  - Metformin improves glucose, lipid metabolism, and reduces blood pressure in
      hypertensive, obese women.
AB  - OBJECTIVE: To determine the effects of metformin on blood pressure, left
      ventricular mass, and some metabolic and endocrine parameters in nondiabetic,
      obese, hypertensive women. RESEARCH DESIGN AND METHODS: Twelve obese,
      nondiabetic, hypertensive women received 850 mg metformin 2 times/day for 12 wk
      and placebo for another 12 wk, according to a double-blind, cross-over,
      randomized design. All patients were hospitalized 4 times, i.e., before
      randomization and after each treatment (metformin or placebo), to conduct
      metabolic and cardiovascular investigations (oral glucose tolerance test,
      euglycemic clamp associated with indirect calorimetry, and echocardiography).
      RESULTS: Fasting glucose, HbA1c, fasting and glucose-stimulated insulin, blood
      pressure and left ventricular mass, cholesterol, triglycerides, and fibrinogen
      decreased significantly after metformin treatment, whereas high-density
      lipoprotein cholesterol increased. The improvement in glucose metabolism resulted
      from increased sensitivity to insulin. CONCLUSIONS: These findings suggest that
      metformin treatment in obese, nondiabetic, hypertensive women produces a more
      favorable cardiovascular risk profile.

PMID- 8269799
TI  - Disruptive effects of acute hypoglycemia on speed of cognitive and motor
      performance.
AB  - OBJECTIVE: To directly examine whether hypoglycemia differentially slows
      cognitive versus motor function, to evaluate the reliability of hypoglycemic
      related slowing, and to examine factors contributing to individual differences.
      RESEARCH DESIGN AND METHODS: IDDM subjects (n = 10) were administered a pure
      cognitive and a pure motor neuropsychological test at euglycemia (5.4 mmol),
      blood glucose nadir (2.6 mmol), postnadir (3.6 mmol), and again at euglycemia
      (6.7 mmol). To assess the practice effect, matched control subjects were tested
      at similar time intervals. RESULTS: Concurrent and test-retest reliability for
      all tests was robust (r = 0.68-0.94). Only cognitive tasks demonstrated
      impairment at nadir (P < 0.04). Individual differences, in terms of cognitive
      impairment, were significantly correlated with levels of blood glucose at nadir
      and baseline performance. CONCLUSIONS: Cognitive tasks appear to be more
      sensitive to neuroglycopenia than motor tasks. Cognitive impairment caused by
      hypoglycemia is reliable and differs across subjects. Individuals who show
      reliable sensitivity to cognitive impairments of hypoglycemia should avoid
      moderately low blood glucose levels.

PMID- 8269800
TI  - Treatment of hypertension in diabetes.

PMID- 8269801
TI  - Lp(a) and insulin dose in IDDM.

PMID- 8269802
TI  - Is there or is there not a relationship between Lp(a) and insulin dose in IDDM?

PMID- 8269803
TI  - Assessing risk factors when screening for diabetes mellitus.

PMID- 8269804
TI  - Prospective study of asymmetric retinopathy as a predictor of brain infarction in
      diabetes mellitus.

PMID- 8269805
TI  - Effect of eicosapentaenoic acid ethyl on urine albumin excretion in NIDDM.

PMID- 8269806
TI  - An unsuspected factor contributing to pizza hyperglycemia.

PMID- 8269807
TI  - The pizza saga.

PMID- 8269808
TI  - Change of lipoprotein(a) and coagulative or fibrinolytic parameters in diabetic
      patients with nephropathy.

PMID- 8269809
TI  - Insulin administration via a subcutaneous catheter. Effects on absorption.

PMID- 8269810
TI  - Utility of routine ophthalmologic examination in patients with gestational
      diabetes mellitus.

PMID- 8269812
TI  - Importance of serum cholesterol level in development of diabetic autonomic
      neuropathy.
AB  - Changes of cardiac beat-to-beat variation (BBV)--an index of autonomic nerve
      function--were examined on 2 occasions in an interval of 3.7-5.9 years in 33
      diabetics. A total of 204 healthy people, ranging from 11 to 88 years of age,
      were also subjected to the BBV measurement as controls. In diabetics, a lower
      rate of change of BBV than the control value was considered as deterioration.
      Glycohemoglobin was measured every month. The mean of serum cholesterol on the 2
      occasions nearest to each time BBV examination was taken for the evaluation of
      cholesterol level. No significant difference was observed in the control state of
      blood glucose in terms of glycohemoglobin between the groups with and without BBV
      deterioration. In 20 subjects with normal cholesterol level, 11 showed a BBV
      deterioration, and in 13 subjects with abnormal cholesterol level 12 deteriorated
      in BBV. Therefore, diabetics with normal serum cholesterol level did not seem to
      exacerbate autonomic neuropathy in terms of BBV.

PMID- 8269811
TI  - Polymorphonuclear neutrophils adherence, superoxide anion (O2-) production and
      HBA1 level in diabetic patients.
AB  - It was established that metabolic disturbances accompanying the impairment of
      diabetes control induced polymorphonuclear neutrophil (PMN) activation.
      Therefore, we evaluated the influence of diabetes control, measured as HbA1,
      level on superoxide anions production and neutrophils adherence to foreign
      surface. Twenty patients with insulin-dependent or non-insulin-dependent diabetes
      being in different state of metabolic control were studied. It was revealed that
      PMN from diabetics demonstrated significantly increased unstimulated superoxide
      anion production (11.07 +/- 1.25 vs. 4.15 +/- 1.24 nmol O2-/10(6) PMN/10 min).
      Stimulated O2- production did not reach the same levels as controls (21.80 +/-
      1.34 vs. 23.67 +/- 4.36 nmol O2-/10(6) PMN/10 min). There were highly significant
      correlations between unstimulated O2- production and HbA1, levels (r = 0.86).
      Adherence of diabetic PMN suspended in autologous plasma was significantly
      increased in comparison to controls (12.76 +/- 1.20 vs. 6.04 +/- 1.99 cells/mm2).
      However, these data did not correlate with HbA1 level (r = 0.06). In conclusion
      our results seems to indicate that metabolic control of diabetes influence PMN
      function.

PMID- 8269813
TI  - Forearm arterial vascular responsiveness in insulin-dependent diabetic subjects.
AB  - The vascular reactivity of forearm arterioles was measured in 16 control subjects
      (C) and 30 insulin-dependent diabetic (IDDM) subjects, 16 of whom were shown to
      have microvascular and/or neuropathic complications (DC) including 8 with
      autonomic neuropathy (DCa) and 14 were shown to be free of complications (DNC).
      Forearm blood flow was measured by strain gauge plethysmography basally,
      following a cold pressor stress and following a period of arterial occlusion
      (reactive hyperaemia). The tests were repeated 24 h later following aspirin
      treatment. Both C and DNC showed a significant reduction in blood flow in the
      cold pressor test (C 0.64 +/- 0.12, DNC 0.89 +/- 0.22 ml/100 ml forearm
      tissue/min reduction in flow P < 0.005), while DC showed no significant response.
      Reactive hyperaemia was significantly greater in C than in DNC or DC (8.37 +/-
      1.14, 5.51 +/- 1.27 and 4.95 +/- 0.75 ml/100 ml tissue/min, respectively, P <
      0.02). In the DC group, DCa had significantly less response than those without
      autonomic neuropathy. Aspirin treatment restored the response of DNC but not DC
      to normal, suggesting that the abnormality in the former group may have been due
      to overproduction of a vasoconstrictive cyclooxygenase product (such as
      thromboxane A2). It is concluded that the abnormalities of vasomotor responses in
      diabetic subjects are complex and are apparently dependent on autonomic
      neuropathy, humoral and perhaps structural changes.

PMID- 8269814
TI  - Clinically important differences in insulin absorption from abdomen in IDDM.
AB  - The absorption of radiolabeled soluble insulin ([125I]Actrapid Human; 10 U) from
      subcutaneous injection sites above (120 mm) and below (40 mm) the umbilicus was
      studied on 2 consecutive days in nine IDDM patients during 180 min. Insulin
      absorption was measured as disappearance of radioactivity by continuous external
      monitoring and as appearance of plasma immunoreactive free insulin (IRI). Adipose
      tissue blood flow (ATBF) was measured concomitantly by the 133Xe-washout
      technique. Plasma glucose was determined. Prior to the injections the depth of
      the subcutaneous fat tissue was determined using ultrasound. Significantly less
      radioactivity remained at the upper site, 42 +/- 5 vs. 60 +/- 6% after 180 min (P
      < 0.001). In accordance with this, injection into the site above vs. below the
      umbilicus resulted in a greater area under curve for plasma insulin, 3306 +/- 493
      vs. 2357 +/- 466 mU/l per min (0-180 min; P < 0.01), and a more pronounced plasma
      glucose-lowering effect (P < 0.05). However, ATBF did not differ significantly
      between the two sites. These data suggest that there are clinically relevant
      differences in insulin absorption within the abdomen. Thus, insulin injection
      into the epigastric area causes more rapid insulin absorption resulting in an
      enhanced plasma glucose-lowering effect than injection into the more conventional
      site close beneath the umbilicus.

PMID- 8269815
TI  - Early complications in type 1 diabetes: central nervous system alterations
      preceded kidney abnormalities.
AB  - Abnormalities of the central nervous system (CNS), as discerned by
      neuroelectrophysiological studies, and an impaired, charge-related, differential
      filtration of protein at kidney level as evaluated by selective protein
      clearance, have recently been shown in diabetes of short duration and without any
      apparent complication. In order to explore the time of appearance and possible
      correlations, CNS and kidney abnormalities have been evaluated in parallel both
      in short-term and long-standing type 1 diabetic subjects. Two groups of patients
      were studied: Group 1 (no. 15), with no previously known clinical sign of
      complications and less than 5 years from diagnosis; Group 2 (no. 15) with more
      than 10 years of disease and with or without clinical signs of diabetic
      complications. Twenty age and sex comparable normal subjects were included in the
      study (Group 3). Short-latency multimodal evoked potentials (visual-VEP,
      brainstem auditory-BAEP, median and tibial somatosensory m- and t-SEP) and charge
      and/or size selective protein clearances (albumin, anionic immunoglobulins,
      neutral/cationic immunoglobulins) were evaluated. In Group 1, 27% of patients
      showed neurophysiological abnormalities (P < 0.05 vs. Group 3) while one showed
      proteinuria. In Group 2, 60% of patients showed electrophysiological changes (P <
      0.0001 vs. Group 3) while 67% showed abnormal charge or size selective
      proteinuria (P < 0.0001 vs. controls) with a significant association between the
      abnormalities of CNS and of charge selective proteinuria (P < 0.05). Thus, CNS
      abnormalities may be detected even in patients with diabetes of short duration
      and are later associated with subclinical kidney abnormalities. These findings
      stress the value of the multimodal evoked potential evaluation as a sensitive and
      early diagnostic approach to the study of diabetic complications.

PMID- 8269816
TI  - Carotid atherosclerosis in young-aged IDDM associated with diabetic retinopathy
      and diastolic blood pressure.
AB  - To determine whether young patients with IDDM already have atherosclerosis and
      what factors would relate to atherosclerosis, we examined the intimal-medial
      thickness (IMT) of the common carotid artery by ultrasonography. Subjects were 29
      young patients with IDDM (aged 17-39 years, duration 4-31 years) without manifest
      macroangiopathy and 13 healthy controls of comparable age (22-29 years). The
      carotid artery IMT of young patients with IDDM were significantly higher than
      those of controls (0.60 +/- 0.09 vs. 0.46 +/- 0.02 mm, P < 0.0001). The levels of
      IMT significantly correlated to diastolic blood pressure (r = 0.45, P < 0.02),
      and were higher in those with proliferative retinopathy than those without
      retinopathy (0.66 +/- 0.09 vs. 0.55 +/- 0.08 mm, P < 0.02). The levels of IMT
      showed no significant correlation to the attained age, duration of IDDM, HbA1c,
      systolic blood pressure, and cholesterol level. These findings suggest the
      usefulness of this examination for the early detection of diabetic
      macroangiopathy, and point to a close relationship between microangiopathy and
      macroangiopathy in IDDM.

PMID- 8269817
TI  - Low titer, competitive insulin autoantibodies are spontaneously produced in
      autoimmune diseases of the thyroid.
AB  - The occurrence of multiple endocrine autoimmunity with organ-specific
      autoantibodies is well known. In this study we evaluated the presence of
      competitive insulin autoantibodies (IAA) in immune and non-immune diseases of the
      thyroid, utilizing a sensitive and specific radiobinding assay. We studied 37
      patients with Graves' disease, 44 patients with Hashimoto's thyroiditis, 11
      patients with non-immune thyroid diseases and 30 normal controls. In 5/37
      (13.5%), 7/44 (15.9%) patients with Graves' and Hashimoto's diseases,
      respectively, but in none of those with non-immune thyroid disease or of the
      controls, IAA levels exceeded our upper limit of normal range (50 nunits/ml) (P <
      0.01). Positive IAA levels ranged between 50 and 123 nunits/ml with fluctuation
      of these levels over time. Islet cell antibodies were not detected in any of the
      patients and the controls in the study. No association was found between
      propylthiouracile treatment and level of IAA. In none of 10 IAA-positive patients
      was the early phase insulin secretion of the intravenous glucose tolerance test
      below 46 mu units/ml, and in 2 subjects repeated tests after 3 years showed
      conserved insulin secretion. In conclusion, our findings show that 15% of
      patients with autoimmune thyroid diseases, produce specific IAA which do not seem
      to reflect aggressive beta cell destruction.

PMID- 8269818
TI  - Changes of albumin concentrations in the first morning urine according to age and
      sex in 2990 healthy children and adults.
AB  - This study was performed to clarify the changes in urinary albumin excretion
      according to age and sex in healthy subjects, for the appropriate judgment of
      microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Concentrations of
      albumin in the first morning urine from 2990 healthy individuals (1713 males,
      1277 females) aged from 6 to 39 years were measured by turbidimetry immunoassay.
      Reference values of the concentrations for each age group were obtained from the
      95% confidence limits from the distribution simulated by the chi 2-test (k = 1).
      Reference values were 1.3-2.2 mg/dl in children aged 6-11 years. Values for
      females increased significantly from 22 mg/dl at age 11 years to 3.9 mg/dl at age
      12 years (P < 0.0001) and those of males increased gradually from 1.7 mg/dl at
      age 11 years to 3.9 mg/dl at age 16 years. There were significant differences
      between males and females at the ages of 12 (P < 0.0001), 13 (P < 0.0001), and 14
      (P < 0.0007). After 17 years, the values decreased from 3.9 mg/dl to 3.3 mg/dl in
      females, and to 2.9 mg/dl in males. We conclude that reference values of urinary
      albumin excretion change according to age and sex, which should be taken into
      consideration in the assessment of diabetic nephropathy in IDDM.

PMID- 8269819
TI  - Pulmonary function in diabetic children with and without persistent
      microalbuminuria.
AB  - The principal spirometric and plethysmographic parameters were measured in 68 (38
      female) diabetic children and adolescents, aged from 6.01 to 22.00 years; their
      duration of disease ranged from 1 to 247 months. Thirty-four patients had
      persistent microalbuminuria. The patients were studied basally and after the
      Bruce test. All the spirometric parameters were normal in all children, with and
      without microalbuminuria. The presence of microalbuminuria seems not to be a risk
      factor for the developing of abnormal pulmonary function.

PMID- 8269820
TI  - An examination of the covariability of subclinical albuminuria in insulin
      dependent diabetes mellitus: implications for monitoring microalbuminuria.
AB  - We examined the covariability of subclinical albuminuria in a cohort of 160
      insulin-dependent diabetics who underwent simultaneous measurements of overnight
      urinary albumin excretion rate (UAV) and several clinical variables on 7
      occasions over a period of 18 months. After allowing for within-patient
      correlation between visits, significant within-patient associations were found
      between UAV and variations in tobacco consumption (regression coefficient =
      0.006, S.E. = 0.002, P = 0.02), insulin dose (regression coefficient = 0.003,
      S.E. = 0.001, P = 0.01) and creatinine clearance (regression coefficient = 0.776,
      S.E. = 0.047, P < 0.0001); the association between UAV and creatinine clearance
      was not influenced by adjusting for urine flow rate. No significant associations
      were found between UAV and changes in blood pressure, glycaemic control or other
      variables. We then focused on 33 patients with intermittent microalbuminuria,
      defined as a UAV > 30 micrograms/min on at least one occasion, but not exceeding
      3 consecutive occasions. These patients had a total of 52 episodes of
      microalbuminuria which were significantly associated at the 5% level with
      increases in creatinine clearance (P = 0.02), but not with changes in other
      variables. Our findings did not differ in patients with intermittent
      microalbuminuria defined with reference to a cut-off UAV of 20 micrograms/min. We
      conclude that changes in glomerular filtration rate (as reflected by creatinine
      clearance) may partly account for the within-patient variability in subclinical
      albuminuria in insulin-dependent diabetics, and that variables routinely measured
      in the clinic are not useful for deciding when to monitor patients for
      microalbuminuria.

PMID- 8269821
TI  - Psychosocial correlates of glycemic control: the Pittsburgh Epidemiology of
      Diabetes Complications (EDC) Study.
AB  - The psychosocial correlates of glycemic control were examined in an incident
      cohort of childhood onset insulin-dependent diabetic subjects aged 18 years or
      older (n = 592). Glycosylated hemoglobin was measured at subjects' clinical
      examination, and questionnaires on diabetes self-care activity, barriers to
      regimen adherence and social support were completed. Demographic information was
      also collected. Glycosylated hemoglobin (GHb) was correlated with age, income and
      educational attainment (correlations coefficients between -0.1 and -0.2; P <
      0.01), suggesting that older, more educated and wealthier patients have better
      glycemic control. GHb was also inversely associated with the degree of self-care
      activity (r = -0.11; P < 0.01), in particular administering injections at the
      recommended times and the frequency of performing blood/urine tests. Factors
      related to self-care behavior were identified, and included degree of social
      support (r = 0.14; P < 0.001) and patients' reports of difficulties adhering to
      their self-care regimen (r = -0.3; P < 0.0001). Gender was also related to self
      care activities, with women reporting more self-care behavior than men (mean self
      care scores 17.9 +/- 3.7 vs. 16.9 +/- 4.0; P < 0.01). Thus psychosocial factors
      (e.g. low income and education) may have an important effect on glycemic control
      in adults, and also (e.g. social support and adherence difficulties) seem
      particularly important in influencing the performance of self-care. As good
      metabolic control may help avoid the progression of diabetic complications,
      efforts need to be directed towards patients with these characteristics who are
      more likely to experience difficulties with self-care.

PMID- 8269822
TI  - Acute idiopathic scrotal oedema in association with diabetic septic foot.
AB  - Acute idiopathic scrotal oedema was observed in three adult diabetic patients
      with septic foot following life saving above knee guillotine amputation. This is
      a previously unreported association as far as we know and no clue to the
      pathogenesis could be obtained.

PMID- 8269823
TI  - In vitro secretion of interleukin-1 beta and interferon-gamma by peripheral blood
      lymphomononuclear cells in diabetic patients.
AB  - There is evidence that cytokines, in particular interleukin-1 beta (IL-1 beta)
      and interferon-gamma (IFN-gamma) might mediate beta cell destruction in type 1
      diabetes. Therefore the secretion of these cytokines by peripheral blood
      lymphomononuclear cells (PBMNC) was investigated in basal conditions and 48 h
      after stimulation with T-cell mitogen phytohaemagglutinin (PHA) in 33 diabetic
      patients and in 10 normal controls. The patients were divided in 4 groups (Group
      1, 10 controls; Group 2, 13 newly diagnosed type 1 diabetics, the onset had
      occurred from 5 days to 3 months before the study; Group 3, 10 Long Standing (LS)
      type 1 diabetics with duration of the disease between 2 years and 10 years; and
      Group 4, 10 type 2 diabetics). No difference was found among the 4 groups
      considered in IL-1 beta secretion by unstimulated cultures, although the
      percentage of TAC+ cells was significantly higher in type 1 newly diagnosed
      diabetic patients with respect to the LS, the type 2 diabetics and the controls.
      After PHA stimulation a significant increase of IL-1 beta was found in newly
      diagnosed type 1 diabetic patients in comparison with the control subjects, the
      LS and type 2 diabetic patients (P < 0.001). The supernatants of newly diagnosed
      type 1 diabetics also showed a significant reduction in IFN-gamma production both
      in basal (P < 0.01) and in stimulated conditions (P < 0.001) in comparison with
      the controls, the LS (P < 0.002 in basal, and P < 0.001 in stimulated conditions)
      and the type 2 diabetic patients (P < 0.001 both in basal and stimulated
      conditions).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269824
TI  - Sex differences in glycated hemoglobin in diabetic and non-diabetic C57BL/6 mice.
AB  - Pathophysiological implications of gender may be important in a number of disease
      states. We therefore decided to study the influence of gender on glycation in
      mice. Plasma glucose and glycated hemoglobin levels were determined by ion
      exchange (HbA1c) and/or affinity chromatography (GHb) in C57BL/6 ob/ob mice
      during the onset and subsequent decline of hyperglycemia. In preweanling ob/ob
      mice, glucose and glycated hemoglobin concentrations were equal to those of lean
      sex-matched controls. Shortly after weaning, plasma glucose in ob/ob mice
      increased to reach a maximum between 2 and 3 months of age, then declined over
      the next several weeks to levels within the range of lean mice. HbA1c values were
      closely associated with the glycemic changes. Male mice of both phenotypes
      consistently had higher values of glycated hemoglobin at a given glucose value
      than did females. Disappearance rates of chromium-labeled erythrocytes were
      slightly higher in lean female mice than in other subgroups but after correcting
      for phenotype/sex differences in blood volume, no phenotype or gender differences
      in RBC lifespan were observed. We conclude that there are gender differences in
      glycation of hemoglobin in mice and that factors other than RBC turnover are
      associated with the gender effects in both obese and lean mice.

PMID- 8269825
TI  - Calcium antagonists for cardiovascular disease.

PMID- 8269826
TI  - Formestane for advanced breast cancer in postmenopausal women.

PMID- 8269827
TI  - [Laparoscopic adrenalectomy].
AB  - Between June and September 1993, laparoscopic adrenalectomy was indicated in five
      patients (three women, two men; aged 25-50 years). Three had a phaeochromocytoma,
      two had an adenoma (Conn's syndrome). Four of the five tumours were localized to
      the right adrenal gland, one to the left. Tumour diameter ranged from 3 to 5 cm.
      The laparoscopic procedure was successful in four of the patients (three right,
      one left). In the fifth case the operations had to be completed by conventional
      surgery, because of non-controllable haemorrhage. Duration of operation ranged
      between 165 and 360 min for right adrenalectomy and was 135 min for the left one.
      Rapid convalescence, lower dose of pain-killing drug required, short hospital
      stay and good cosmetic results characterized the postoperative course after the
      laparoscopic procedure. This technique thus opens up new perspectives for adrenal
      surgery.

PMID- 8269828
TI  - [Unilateral autonomous aldosterone production in hyperaldosteronism suppressible
      by dexamethasone].
AB  - A 21-year-old woman with weight loss, palpitations and facial flush was found to
      have hypertension (up to 200/130 mm Hg) and mild hyperkalaemia (3.4 mmol/l).
      Extensive diagnostic tests revealed hyperaldosteronism with contrast storing in
      the right adrenal gland on scintigraphy after injection of dexamethasone (2 mg
      daily for one week). The hyperaldosteronism could not be suppressed by
      dexamethasone. Analysis of venous blood separately from each side pointed to
      aldosterone production in the right adrenal (right renal vein: 80 ng/dl, drainage
      area of the right adrenal vein: 114 ng/dl, left renal vein: too low to measure).
      The right adrenal gland was removed. No adenoma was found histologically. After
      the operation the aldosterone level was reduced and the blood pressure
      transiently fell. But both had risen again after 3 months. Renewed tests revealed
      dexamethasone-remediable hyperaldosteronism. On treatment with hydrocortisone (15
      5-5 mg) and 50 mg metoprolol the patient became normotensive without any other
      medication.

PMID- 8269829
TI  - [Sepsis and spondylodiscitis caused by Salmonella enteritidis].
AB  - Four weeks after an attack of bronchopneumonia a 59-year-old veterinary surgeon
      developed backache. The chest radiograph showed an impression fracture of the
      11th thoracic vertebra. Persisting fever led to hospitalization. Several blood
      cultures grew Salmonella enteritidis. Computed tomography demonstrated a fracture
      of the 11th thoracic vertebra with osteolytic infiltration and paravertebral soft
      tissue infiltration. Bone scan showed band-like contrast enhancement in the same
      area. Treatment at first consisted of Ciprofloxacin, 200 mg twice daily
      intravenously for 5 days, then 750 mg orally twice daily for 3 months. The fever
      regressed within a few days. Sclerosis of the affected vertebral area became
      radiologically evident after 6 weeks. After this the patient was allowed to move
      around again, without any further problems.

PMID- 8269830
TI  - [Proteinuria].

PMID- 8269831
TI  - [Adenosine--an endogenous protective substance in the heart].

PMID- 8269832
TI  - [Nobel Prize for Medicine 1993].

PMID- 8269833
TI  - [Coenzyme Q10 and heart disease].

PMID- 8269834
TI  - [HIV: how big is the residual risk?].

PMID- 8269835
TI  - [Decline in oxygen saturation following sublingual administration of nifedipine].

PMID- 8269836
TI  - [Risk of hemorrhage in penicillin therapy].

PMID- 8269837
TI  - [Oral administration of diazepam for the prevention of febrile convulsions in
      young children].

PMID- 8269838
TI  - Genetic characterization of the multipotent dedifferentiated state of pigmented
      epithelial cells in vitro.
AB  - Retinal pigmented epithelial cells (PECs) of chicken embryos extensively and
      almost synchronously transdifferentiate into lens cells in medium containing
      phenylthiourea and testicular hyaluronidase, passing through the bipotent
      dedifferentiated state. We have isolated genes that are expressed specifically by
      either pigment or lens cells and analyzed their expression in the
      transdifferentiation process. The expression of some proto-oncogenes was also
      studied. In the dedifferentiation process, expression of the c-myc gene was
      enhanced and the transcription of PEC-specific genes (MMP115, pP344) was
      completely repressed. However, transcription of lens-specific genes (alpha-, beta
      and delta-crystallins genes) remained silent in dedifferentiated pigment cells.
      Activation of len- or PEC-specific genes occurred only in conditions permissive
      for lens or PEC differentiation, respectively. These results indicated that lens
      transdifferentiation from PECs proceeds through a multipotent (or at least
      bipotent) intermediate cell state in which the c-myc gene is activated, but
      neither PEC- nor lens-specific genes are expressed.

PMID- 8269839
TI  - A repressor controls the timing and spatial localisation of stalk cell-specific
      gene expression in Dictyostelium.
AB  - The ecmA and ecmB genes of Dictyostelium encode related extracellular matrix
      proteins and both are induced by DIF, the stalk cell-specific morphogen. The ecmA
      gene is expressed throughout the prestalk region of the migrating slug but only
      later, at culmination, do the prestalk cells express the ecmB gene. Expression of
      the ecmB gene is induced at the entrance to the stalk tube and we have identified
      two, apparently redundant, promoter elements that control this process. They act
      as repressors, preventing transcription in the tip of the migrating slug and the
      apical papilla of the culminant. They have a semi-palindromic consensus sequence
      TTGnCAA, where n is in one case 2 and in the other 4 bp. Either element alone is
      able to repress ecmB promoter activity in prestalk cells. Introduction of a
      single repressor element into the promoter of the ecmA gene changes its
      expression pattern to resemble that of the ecmB gene. Mutant elements, where n is
      altered, cause repression during the slug stage but allow premature ecmB
      expression during culmination; suggesting that the effective strength of the
      inductive signal may increase during culmination. Inhibition of cAMP-dependent
      protein kinase (PKA) in prestalk cells blocks both stalk cell maturation and ecmB
      gene expression. We show that the block to gene expression correlates precisely
      with the presence of a functional repressor element and this is consistent with
      the notion that expression of the ecmB gene is controlled by a PKA-dependent
      release from transcriptional repression.

PMID- 8269840
TI  - Regulative capacity of the cranial neural tube to form neural crest.
AB  - In avian embryos, cranial neural crest cells emigrate from the dorsal midline of
      the neural tube shortly after neural tube closure. Previous lineage analyses
      suggest that the neural crest is not a pre-segregated population of cells within
      the neural tube; instead, a single progenitor in the dorsal neural tube can
      contribute to neurons in both the central and the peripheral nervous systems
      (Bronner-Fraser and Fraser, 1989 Neuron 3, 755-766). To explore the relationship
      between the 'premigratory' neural crest cells and the balance of the cells in the
      neural tube in the midbrain and hindbrain region, we have challenged the fate of
      these populations by ablating the neural crest either alone or in combination
      with the adjoining ventral portions of the neural tube. Focal injections of the
      vital dye, DiI, into the neural tissue bordering the ablated region demonstrate
      that cells at the same axial level, in the lateral and ventral neural tube,
      regulate to reconstitute a population of neural crest cells. These cells emigrate
      from the neural tube, migrate along normal pathways according to their axial
      level of origin and appear to give rise to a normal range of derivatives. This
      regulation following ablation suggests that neural tube cells normally destined
      to form CNS derivatives can adjust their prospective fates to form PNS and other
      neural crest derivatives until 4.5-6 hours after the time of normal onset of
      emigration from the neural tube.

PMID- 8269841
TI  - Expression of synaptotagmin in Drosophila reveals transport and localization of
      synaptic vesicles to the synapse.
AB  - Synaptotagmin is a synaptic vesicle-specific integral membrane protein that has
      been suggested to play a key role in synaptic vesicle docking and fusion. By
      monitoring Synaptotagmin's cellular and subcellular distribution during
      development, it is possible to study synaptic vesicle localization and transport,
      and synapse formation. We have initiated the study of Synaptotagmin's expression
      during Drosophila neurogenesis in order to follow synaptic vesicle movement prior
      to and during synapse formation, as well as to localize synaptic sites in
      Drosophila. In situ hybridizations to whole-mount embryos show that synaptotagmin
      (syt) message is present in the cell bodies of all peripheral nervous system
      neurons and many, if not all, central nervous system neurons during neurite
      outgrowth and synapse formation, and in mature neurons. Immunocytochemical
      staining with antisera specific to Synaptotagmin indicates that the protein is
      present at all stages of the Drosophila life cycle following germ band
      retraction. In embryos, Synaptotagmin is only transiently localized to the cell
      body of neurons and is transported rapidly along axons during axonogenesis. After
      synapse formation, Synaptotagmin accumulates in a punctate pattern at all
      identifiable synaptic contact sites, suggesting a general role for Synaptotagmin
      in synapse function. In embryos and larvae, the most intense staining is found
      along two broad longitudinal tracts on the dorsal side of the ventral nerve cord
      and the brain, and at neuromuscular junctions in the periphery. In the adult
      head, Synaptotagmin localizes the discrete regions of the neurophil where
      synapses are predicted to occur. These data indicate that synaptic vesicles are
      present in axons before synapse formation, and become restricted to synaptic
      contact sites after synapses are formed. Since a similar expression pattern of
      Synaptotagmin has been reported in mammals, we propose that the function of
      Synaptotagmin and the mechanisms governing localization of the synaptic vesicle
      before and after synapse formation are conserved in invertebrate and vertebrate
      species. The ability to mark synapses in Drosophila should facilitate the study
      of synapse formation and function, providing a new tool to dissect the molecular
      mechanisms underlying these processes.

PMID- 8269842
TI  - A fourth human MEF2 transcription factor, hMEF2D, is an early marker of the
      myogenic lineage.
AB  - The transition from multipotent mesodermal precursor to committed myoblast and
      its differentiation into a mature myocyte involve molecular events that enable
      the cell to activate muscle-specific genes. Among the participants in this
      process is the myocyte-specific enhancer factor 2 (MEF2) family of tissue
      restricted transcription factors. These factors, which share a highly conserved
      DNA-binding domain including a MADS box, are essential for the expression of
      multiple muscle genes with cognate target MEF2 sites in cis. We report here a new
      human MEF2 factor, hMEF2D, which is unique among the members of this family in
      that it is present not only in myotubes but also in undifferentiated myoblasts,
      even before the appearance of myogenin. hMEF2D comprises several alternatively
      spliced products of a single gene, one of which is the human homolog of the
      Xenopus SRF-related factor SL-1. Like its relatives, cloned hMEF2D is capable of
      activating transcription via sequence-specific binding to the MEF2 site,
      recapitulating endogenous tissue-specific MEF2 activity. Indeed, while MEF2D
      mRNAs are ubiquitous, the protein is highly restricted to those cell types that
      contain this activity, implicating posttranscriptional mechanisms in the
      regulation of MEF2D expression. Alternative splicing may be important in this
      process: two alternative MEF2D domains, at least one of which is specifically
      included during myogenic differentiation, also correlate precisely with
      endogenous MEF2 activity. These findings provide compelling evidence that MEF2D
      is an integral link in the regulatory network for muscle gene expression. Its
      presence in undifferentiated myoblasts further suggests that it may be a mediator
      of commitment in the myogenic lineage.

PMID- 8269843
TI  - Ectopic expression of seven-up causes cell fate changes during ommatidial
      assembly.
AB  - During Drosophila ommatidial development, a single cell is selected within the
      ommatidial cluster to become the R7 photoreceptor neuron. The seven-up gene has
      been shown to play a role in this process by preventing four other photoreceptor
      precursors, R3/R4/R1/R6, from adopting the R7 cell fate. The seven-up gene
      encodes a steroid receptor-like molecule that is expressed only in those four
      cells that require seven-up function in the developing Drosophila ommatidium. We
      have examined the functional significance of the spatially restricted expression
      of seven-up by misexpressing seven-up isoforms. As expected from the function
      that seven-up performs in R3/R4/R1/R6, ubiquitous expression of seven-up causes
      transformation of the R7 cell to an R1-R6 cell fate. In addition, depending on
      the timing and spatial pattern of expression, various other phenotypes are
      produced including the loss of the R7 cell and the formation of extra R7 cells.
      Ubiquitous expression of seven-up close to the morphogenetic furrow interferes
      with R8 differentiation resulting in failure to express the boss protein, the
      ligand for the sevenless receptor tyrosine kinase, and the R7 cell is lost
      consequently. Extra R7 cells are formed by recruiting non-neuronal cone cells as
      photoreceptor neurons in a sevenless and bride of sevenless independent way.
      Thus, the spatiotemporal pattern of seven-up expression plays an essential role
      in controlling the number and cellular origin of the R7 neuron in the ommatidium.
      Our results also suggest that seven-up controls decisions not only between
      photoreceptor subtypes, but also between neuronal and non-neuronal fates.

PMID- 8269845
TI  - Embryonic wing and leg motoneurons have intrinsically different survival
      properties.
AB  - Although spinal motoneurons in the chick embryo are born in a rostro-caudal
      gradient, the timing of their naturally occurring cell death varies in the
      opposite sense: brachial motoneurons (MNs) die later than lumbar MNs. We used in
      vitro methods to determine whether this difference results from factors intrinsic
      or extrinsic to the MNs. Embryonic MNs were purified from E5 lumbar and brachial
      spinal cord by a method that enriches for MNs with heightened trophic
      requirements; they were cultured in serum-free medium. In the absence of muscle
      extract, death of both populations was rapid; similar results are obtained in ovo
      after limb ablation. In the presence of muscle extracts, however, lumbar MNs
      always died more rapidly than brachial MNs, as in the normal embryo. We tested
      the ability of wing and leg bud extracts to provide trophic factors for MNs in
      culture. MNs from a given level responded equally well to wing or leg extracts.
      However, dose-response studies showed that near-maximal survival of brachial MNs
      was obtained with lower concentrations of limb extract than those required for
      optimal survival of lumbar MNs. These results suggest that the delayed apoptosis
      in the brachial MN population is not a result of differing peripheral trophic
      support, but is intrinsically programmed, at least partially through a higher
      sensitivity to trophic factors.

PMID- 8269844
TI  - Selective accumulation of MyoD and myogenin mRNAs in fast and slow adult skeletal
      muscle is controlled by innervation and hormones.
AB  - Each of the myogenic helix-loop-helix transcription factors (MyoD, Myogenin, Myf
      5, and MRF4) is capable of activating muscle-specific gene expression, yet
      distinct functions have not been ascribed to the individual proteins. We report
      here that MyoD and Myogenin mRNAs selectively accumulate in hindlimb muscles of
      the adult rat that differ in contractile properties: MyoD is prevalent in fast
      twitch and Myogenin in slow twitch muscles. The distribution of MyoD and Myogenin
      transcripts also differ within a single muscle and correlate with the proportions
      of fast glycolytic and slow oxidative muscle fibres, respectively. Furthermore,
      the expression of a transgene consisting of a muscle-specific cis-regulatory
      region from the myoD gene controlling lacZ was primarily associated with the fast
      glycolytic fibres. Alteration of the fast/slow fibre type distribution by thyroid
      hormone treatment or by cross-reinnervation resulted in a corresponding
      alteration in the MyoD/Myogenin mRNA expression pattern. These findings show that
      the expression of specific myogenic helix-loop-helix regulators is under the
      control of innervation and humoral factors and may mediate differential control
      of contractile protein gene expression in adult muscle.

PMID- 8269846
TI  - A central role for microtubules in the differentiation of Drosophila oocytes.
AB  - Drosophila oocytes develop within cysts containing 16 cells that are
      interconnected by cytoplasmic bridges. Although the cysts are syncytial, the 16
      cells differentiate to form a single oocyte and 15 nurse cells, and several mRNAs
      that are synthesized in the nurse cells accumulate specifically in the oocyte. To
      gain insight into the mechanisms that generate the cytoplasmic asymmetry within
      these cysts, we have examined cytoskeletal organization during oocyte
      differentiation. Shortly after formation of the 16 cell cysts, a prominent
      microtubule organizing center (MTOC) is established within the syncytial
      cytoplasm, and at the time the oocyte is determined, a single microtubule
      cytoskeleton connects the oocyte with the remaining 15 cells of each cyst.
      Recessive mutations at the Bicaudal-D (Bic-D) and egalitarian (egl) loci, which
      block oocyte differentiation, disrupt formation and maintenance of this polarized
      microtubule cytoskeleton. Microtubule assembly-inhibitors phenocopy these
      mutations, and prevent oocyte-specific accumulation of oskar, cyclin B and 65F
      mRNAs. We propose that formation of the polarized microtubule cytoskeleton is
      required for oocyte differentiation, and that this structure mediates the
      asymmetric accumulation of mRNAs within the syncytial cysts.

PMID- 8269847
TI  - Postembryonic proliferation of neuroendocrine cells expressing adipokinetic
      hormone peptides in the corpora cardiaca of the locust.
AB  - Neuroendocrine glands that synthesize and secrete peptide hormones regulate the
      levels of these peptide messengers during development. In this article we
      describe a mechanism for regulating neuropeptide levels in the corpora cardiaca
      of the locust Schistocerca gregaria, a neuroendocrine gland structurally
      analogous to the vertebrate adenohypophysis. A set of five colocalized peptide
      hormones of the adipokinetic hormone family is synthesized in intrinsic
      neurosecretory cells in the corpora cardiaca. During postembryonic development
      there are progressive changes in the absolute and relative levels of these five
      peptide hormones. We show that the ability of the gland to increase peptide
      synthesis is due to a 100-fold increase in the number of cells which make up the
      gland. The gland grows by the addition of new cells derived from symmetrical
      division of undifferentiated precursor cells within the corpora cardiaca. We
      show, using double-label immunocytochemistry, that cells born in the glandular
      lobe mature into cells that express adipokinetic hormone peptides. The pattern of
      cell birth and peptide expression can account for the dramatic increase in
      postembryonic peptide levels.

PMID- 8269848
TI  - A role for the Drosophila segment polarity gene armadillo in cell adhesion and
      cytoskeletal integrity during oogenesis.
AB  - The epithelial sheet is a structural unit common to many tissues. Its
      organization appears to depend on the function of the multi-protein complexes
      that form adherens junctions. Elegant cell biological experiments have provided
      support for hypotheses explaining the function of adherens junctions and of their
      components. These systems, however, lack the ability to test function within an
      entire organism during development. The realization that the product of the
      Drosophila segment polarity gene armadillo is related to the vertebrate adhesive
      junction components plakoglobin and beta-catenin led to the suggestion that
      armadillo might provide a genetic handle to study adhesive junction structure and
      function. An examination of the potential function of Armadillo in cell-cell
      adhesive junctions was initiated using the Drosophila ovary as the model system.
      We examined the distribution of Armadillo in the Drosophila ovary and
      demonstrated that this localization often parallels the location of cell-cell
      adhesive junctions. The consequences of removing armadillo function from the germ
      line cells of the ovary were also examined. Germ-line armadillo mutations appear
      to disrupt processes requiring cell adhesion and integrity of the actin
      cytoskeleton, consistent with a role for Armadillo in cell-cell adhesive
      junctions. We have also used armadillo mutations to examine the effects on
      ovarian development of altering the stereotyped cell arrangements of the ovary.
      The implications of these results for the role of adhesive junctions during
      development are discussed.

PMID- 8269849
TI  - Expression of relB transcripts during lymphoid organ development: specific
      expression in dendritic antigen-presenting cells.
AB  - We have studied the expression of the relB gene during mouse development using in
      situ hybridization and immunocytochemical analysis. The results show that the
      expression of the relB gene is highly restricted to a subpopulation of cells that
      colonize the lymphoid tissues and that appear very late during the process of
      hematopoietic diversification. RNA transcripts of relB are very low or
      undetectable in early and late embryos. Low relB expression is observed in the
      thymus at late stages of embryogenesis but rapidly increases after birth. In
      adult lymphoid tissues, relB is detected in the medullary region of the thymus,
      the periarterial lymphatic sheaths of the spleen, and the deep cortex of the
      lymph nodes, which correspond to the regions where T cells of mature phenotype
      and interdigitating dendritic cells are present. Using double immunofluorescent
      labeling of thymic cell suspensions, we have identified the interdigitating
      dendritic cells as the target of RelB expression. These cells are part of a
      system of antigen-presenting cells that function in the induction of several
      immune responses, such as, tolerance, sensitization of MHC-restricted T cells,
      rejection of organ transplants and formation of T-dependent antibodies. Our
      observations indicate that RelB may play a particular role in the signal
      transduction pathway that regulate dendritic cell differentiation and its
      cellular responses.

PMID- 8269850
TI  - RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization.
AB  - Deployment of the bicoid morphogen gradient in early Drosophila embryos requires
      the prelocalization of bicoid mRNA to the anterior pole of the egg. This anterior
      localization is mediated by a cis-acting localization signal contained within the
      3' untranslated region of the bicoid mRNA. Here we use a series of bicoid
      transgenes carrying small deletions in the 3' untranslated region to survey for
      functional elements that constitute the localization signal. We identify and
      characterize one essential element, BLE1, which specifically directs the early
      steps of localization. In addition, we find that many deletions within the bicoid
      mRNA 3' untranslated region impair but do not prevent localization. One such
      deletion specifically interferes with a later step in localization. Thus the
      bicoid mRNA localization signal appears to consist of multiple different
      elements, each responsible for different steps in the localization process.

PMID- 8269851
TI  - Mutations affecting the cytoskeletal organization of syncytial Drosophila
      embryos.
AB  - Cytoplasmic organization, nuclear migration, and nuclear division in the early
      syncytial Drosophila embryo are all modulated by the cytoskeleton. In an attempt
      to identify genes involved in cytoskeletal functions, we have examined a
      collection of maternal-effect lethal mutations induced by single P-element
      transposition for those that cause defects in nuclear movement, organization, or
      morphology during the syncytial embryonic divisions. We describe three mutations,
      grapes, scrambled, and nuclear-fallout, which define three previously
      uncharacterized genes. Females homozygous for these mutations produce embryos
      that exhibit extensive mitotic division errors only after the nuclei migrate to
      the surface. Analysis of the microfilament and microtubule organization in
      embryos derived from these newly identified mutations reveal disruptions in the
      cortical cytoskeleton. Each of the three mutations disrupts the actin-based
      pseudocleavage furrows and the cellularization furrows in a distinct fashion. In
      addition to identifying new genes involved in cytoskeletal organization, these
      mutations provide insights into cytoskeletal function during early Drosophila
      embryogenesis.

PMID- 8269852
TI  - Staging of gastrulating mouse embryos by morphological landmarks in the
      dissecting microscope.
AB  - We describe and illustrate a set of morphological landmarks for classifying mouse
      embryos by gross morphology from before gastrulation to the beginning of
      organogenesis. These landmarks are visible at the resolution of the dissecting
      microscope in embryos that are intact except for reflexion of Reichert's
      membrane. Adoption of these criteria should facilitate interpretation of both the
      expression patterns of genes and the consequences of experimental manipulation of
      embryos during early postimplantation development.

PMID- 8269853
TI  - Establishment of gut fate in the E lineage of C. elegans: the roles of lineage
      dependent mechanisms and cell interactions.
AB  - The gut of C. elegans derives from all the progeny of the E blastomere, a cell of
      the eight cell stage. Previous work has shown that gut specification requires an
      induction during the four cell stage (Goldstein, B. (1992) Nature 357, 255-257).
      Blastomere isolation and recombination experiments were done to determine which
      parts of the embryo can respond to gut induction. Normally only the posterior
      side of the EMS blastomere contacts the inducing cell, P2. When P2 was instead
      placed in a random position on an isolated EMS, gut consistently differentiated
      from the daughter of EMS contacting P2, indicating that any side of EMS can
      respond to gut induction. Additionally, moving P2 around to the opposite side of
      EMS in an otherwise intact embryo caused EMS's two daughter cells to switch
      lineage timings, and gut to differentiate from the descendents of what normally
      would be the MS blastomere. The other cells of the four cell stage, ABa, ABp, and
      P2, did not form gut when placed in contact with the inducer. To determine
      whether any other inductions are involved in gut specification, timed blastomere
      isolations were done at the two and eight cell stages. In the absence of cell
      contact at the two cell stage, segregation of gut fate proceeded normally at both
      the two and four cell stages. Gut fate also segregated properly in the absence of
      cell contact at the eight cell stage. A model is presented for the roles of
      lineage-dependent mechanisms and cell interactions in establishing gut fate in
      the E lineage.

PMID- 8269854
TI  - Sperm require beta-N-acetylglucosaminidase to penetrate through the egg zona
      pellucida.
AB  - Fertilization in the mouse is initiated by sperm beta 1,4-galactosyltransferase
      (GalTase) binding to terminal N-acetylglucosamine residues on the zona pellucida
      glycoprotein ZP3. Binding of ZP3 induces exocytosis of the sperm acrosome, whose
      contents are believed to digest a penetration slit in the zona matrix through
      which sperm reach the egg. As a consequence of acrosomal exocytosis, GalTase is
      redistributed to the lateral aspect of the sperm head, where its function remains
      unknown. In this location, GalTase could conceivably impede zona penetration by
      binding to N-acetylglucosamine residues exposed on zona pellucida glycoproteins.
      Therefore, in this study we investigated the presence and function of acrosomal
      glycosidases capable of removing the GalTase-binding site from zona pellucida
      glycoproteins. beta-N-acetylglucosaminidase was found at very high levels in
      sperm, being more than 20-fold higher than other glycosidases assayed. The
      specific isozymic variant was identified as beta-hexosaminidase B. beta-N
      acetylglucosaminidase was localized to sperm acrosomes by biochemical and
      indirect immunofluorescence studies and was released during the acrosome
      reaction, as expected for an enzyme involved in zona penetration. To determine
      if, in fact, acrosomal beta-N-acetylglucosaminidase facilitated penetration
      through the zona, an assay was developed using eggs that were rendered incapable
      of triggering the block to polyspermy. A specific competitive inhibitor of beta-N
      acetylglucosaminidase activity, PUGNAC, inhibited sperm penetration of the zona
      in a dose-dependent manner, whereas a closely related beta-glucosidase inhibitor,
      PUGLU, had no effect on zona penetration or on beta-N-acetylglucosaminidase
      activity. Neither glycosidase inhibitor affected sperm motility or induction of
      the acrosome reaction. These results demonstrate that beta-N
      acetylglucosaminidase is found in sperm acrosomes and is released during the
      acrosome reaction, at which time it facilitates sperm penetration through the
      zona. These results also imply that sperm have developed mechanisms to prevent
      the formation of stable interactions between surface receptors and their zona
      pellucida ligands during penetration.

PMID- 8269855
TI  - Expanded: a gene involved in the control of cell proliferation in imaginal discs.
AB  - The expanded gene was first identified by a spontaneous mutation that causes
      broad wings. We have identified an enhancer-trap insertion within expanded and
      used it to generate additional mutations, including one null allele. expanded is
      an essential gene, necessary for proper growth control of imaginal discs and,
      when mutant, causes either hyperplasia or degeneration depending on the disc.
      Wing overgrowth in expanded hypermorphs is limited to specific regions along the
      anterior-posterior and dorsal-ventral axis. expanded encodes a novel 1429 amino
      acid protein that is localized to the apical surface of disc cells and contains
      three potential SH3-binding sites. Together, these observations suggest that the
      Expanded protein engages in protein-protein interactions regulating cell
      proliferation in discs.

PMID- 8269856
TI  - Fertile females of the mole Talpa occidentalis are phenotypic intersexes with
      ovotestes.
AB  - We investigated the origin of XX sex reversal in the insectivorous mole Talpa
      occidentalis. Cytogenetic, histological and hormonal studies indicate that all XX
      individuals analyzed from two different populations are true hermaphrodites, with
      ovotestes. This suggests that XX sex reversal may be the norm in this species.
      The intersexes are functional fertile females and the trait is transmitted and
      maintained in the population. Intersexes lack the Y chromosome gene SRY (sex
      determining region Y gene), shown to be the testis determining gene. These
      results suggest that XX intersex moles may have arisen from a mutation of a gene
      located downstream from SRY/TDY in the testis determining pathway.

PMID- 8269857
TI  - Basic fibroblast growth factor (bFGF) acts intracellularly to cause the
      transdifferentiation of avian neural crest-derived Schwann cell precursors into
      melanocytes.
AB  - We previously found that cultured neural crest-derived cells from embryonic quail
      peripheral nerves, which consist mostly of Schwann cell precursors, gave rise to
      melanocytes following treatment with basic fibroblast growth factor (bFGF) or 12
      O-tetradecanoyl phorbol-13-acetate (TPA). Here, we show that antisense
      deoxyoligonucleotides targeted against two regions of the bFGF mRNA transcript
      blocked this TPA-induced transdifferentiation of Schwann cell precursors. Neither
      sense nor scrambled antisense control oligonucleotides had any effect in this
      regard. TPA increased bFGF protein expression in cell lysates but not in
      conditioned media from these cultures, and this expression was localized to the
      nucleus and cytoplasm. Furthermore, bFGF-neutralizing antibodies and inositol
      hexakisphosphate (InsP6) both inhibited pigmentation caused by exogenous bFGF,
      but had no affect on TPA-induced melanogenesis, suggesting that bFGF is not
      released by these cells. These data indicate that bFGF is necessary for the TPA
      induced transdifferentiation of Schwann cell precursors into melanocytes and that
      bFGF acts via an intracrine mechanism.

PMID- 8269858
TI  - Foetal testes control the prenatal growth and differentiation of the gubernacular
      cones in rabbits--a tribute to the late Professor Alfred Jost.
AB  - Gubernacular cones develop during foetal life in males of various species,
      including many of the common small laboratory animals. Postnatally these papilla
      like organs invert and develop into the muscular cremaster sacs, providing space
      for testis descent. The mechanism governing male-specific development of these
      structures during foetal and postnatal life is unknown but foetal testicular
      androgens or anti-Mullerian hormone are unlikely to be involved. The present
      study of gubernacular cone development in 28-day-old rabbit foetuses castrated 5
      9 days before questions whether foetal testis hormones play any role in these
      developmental processes. The study comprised an analysis of the microscopic
      slides in the legacy of the late Professor Alfred Jost in Paris. Castration at an
      earlier (19 days) or later (23/24 days) day of foetal life interfered with
      gubernacular cone growth and differentiation. Unilateral castration partially
      inhibited ipsilateral gubernacular cone growth. Implantation of a foetal testis
      close to the ovary could induce male-type gubernacular cone growth in females.
      Together the data unequivocally support the concept of foetal testicular hormonal
      control of male-specific gubernacular cone development. Further study is required
      to unravel the nature of the active foetal testicular agent.

PMID- 8269859
TI  - Mesoderm formation in Xenopus ectodermal explants overexpressing Xwnt8: evidence
      for a cooperating signal reaching the animal pole by gastrulation.
AB  - It is demonstrated here that the ability of injected Xwnt8 RNA to trigger
      mesoderm formation in Xenopus presumptive ectoderm (animal caps) depends on the
      time of explantation. Animal caps isolated from Xwnt8 injected embryos at the
      late blastula/early gastrula stages differentiate mesodermal tissues whereas caps
      isolated from early blastula do not. This finding suggests that an endogenous
      signal reaches the animal cap by the late blastula stage and cooperates with
      Xwnt8 to induce mesoderm. Similarly, late animal caps isolated at st. 10 from
      lithium-treated embryos, but not those from control embryos, elongate and express
      muscle-specific actin transcripts. In addition, the data presented suggests that
      the cooperating signal is distributed homogeneously with respect to the future
      dorsoventral axis and may require FGF- and activin-dependent signal transduction
      pathways. These observations support a model in which mesoderm is induced in vivo
      by a combined action of several different signals.

PMID- 8269860
TI  - ES cells have only a limited lymphopoietic potential after adoptive transfer into
      mouse recipients.
AB  - While hematopoietic stem cells from adult and fetal stages of murine development
      are capable of long term reconstitution of all mature blood lineages in vivo,
      embryonic hematopoietic stem cell repopulation in vivo has proved difficult. It
      is thought that there are many fewer hematopoietic stem cells in the embryo than
      in the fetal/adult stages of mouse development and that these cells possess a
      different developmental potential. One source of such cells are embryonic stem
      (ES) cells which can differentiate into most mature blood lineages in vitro. We
      have therefore used transplantation of differentiated ES cells to assess the
      hematopoietic potential of embryonic hematopoietic cells in vivo. We demonstrate
      here that precursors obtained from in vitro cultures of normal ES cells can
      contribute only to restricted and limited hematopoiesis in a mouse without
      leading to tumour formation. Repopulation occurs for greater than 6.5 months at
      levels ranging from 0.1% to 6% in B and T cell lineages in peripheral blood. In
      contrast to in vitro colony data demonstrating the myeloid lineage developmental
      potential of ES cells, no donor-derived myeloid repopulation was observed in CFU
      S assays and no macrophage and mast cells were found in long term repopulated
      recipients. Thus, the hematopoietic potential of ES cells in vivo is limited to
      low levels of repopulation and is restricted to the lymphoid lineage.

PMID- 8269861
TI  - A novel H+ permeability dominating intracellular pH in the early mouse embryo.
AB  - Most cell types are relatively impermeant to H+ and are able to regulate their
      intracellular pH by means of plasma membrane proteins, which transport H+ or
      bicarbonate across the membrane in response to perturbations of intracellular pH.
      Mouse preimplantation embryos at the 2-cell stage, however, do not appear to
      possess specific pH-regulatory mechanisms for relieving acidosis. They are,
      instead, highly permeable to H+, so that the intracellular pH in the acid and
      neutral range is determined by the electrochemical equilibrium of H+ across the
      plasma membrane. When intracellular pH is perturbed, the rate of the ensuing H+
      flux across the plasma membrane is determined by the H+ electrochemical gradient:
      its dependence on external K+ concentration indicates probable dependence on
      membrane potential and the rate depends on the H+ concentration gradient across
      the membrane. The large permeability at the 2-cell stage is absent or greatly
      diminished in the trophectoderm of blastocysts, but still present in the inner
      cell mass. Thus, the permeability to H+ appears to be developmentally regulated.

PMID- 8269862
TI  - Neurotrophic activity in embryonic chick brain: early appearance and differential
      regional distribution.
AB  - Homogenate extracts were prepared from various regions of the embryonic chick
      brain from E6 to E19. The extracts were applied to cultured dorsal root ganglia
      (DRGs), sympathetic ganglion cells, PC12 cells and E5 spinal cord neurons. Potent
      neurotrophic activity with respect to DRGs was found in an extract from the
      forebrain (FBX) from the earliest stage assayed (E6). This activity was
      comparable to that of nerve growth factor (NGF), and it was not appreciably
      altered during later stages. By E8, extracts prepared from the optic lobe also
      induced responsiveness, although to a lesser extent than the FBX and NGF. At E12
      19, extracts from the hippocampus (HCX) and cerebellum (CBX) were also tested.
      Activity found in the HCX resembled that in the FBX, but responsiveness to the
      CBX was similar to that in control (unsupplemented) cultures. The responsiveness
      of sympathetic neurons in the FBX was comparable to that with NGF. The FBX
      induced only moderate differentiation of PC12 cells, and spinal cord neurons were
      not responsive. Antibodies to NGF and basic fibroblast growth factor did not
      diminish the influence of the FBX, and the FBX and NGF when combined had
      synergistic effects. The results demonstrate potent neurotrophin-like activity in
      the embryonic brain at much earlier stages than had previously been seen, with
      differential regional and temporal distributions.

PMID- 8269863
TI  - In vivo proliferative pattern of trembler hypomyelinating Schwann cells is
      modified in culture: an experimental analysis.
AB  - Trembler mouse, a Schwann cell mutation, is characterized by severe
      hypomyelination of peripheral nerves, high Schwann cell proliferation and the
      presence of a multilayered basal lamina which surrounds them. In contrast with
      their continuous in vivo division, mutant Schwann cells prepared from 15-day
      sciatic nerves display a lower proliferation rate in cell culture than normal
      Schwann cells. However, quiescent Trembler Schwann cells are still able to
      respond, as normal Schwann cells, to exogenous mitogens, such as nerve extracts
      and myelin-enriched fractions. In addition, both normal and Trembler Schwann
      cells proliferate in response to Trembler serum. Fibroblast growth factor is not
      the mitogenic factor which stimulates mutant Schwann cell proliferation in vivo,
      since it is absent in Trembler serum and poorly concentrated in Trembler adult
      sciatic nerves. Our results suggest that, in vivo, the serum of Trembler mouse
      probably contains mitogenic factors, not yet characterized, which may trigger the
      permanent division of mutant Schwann cells, in contrast to the quiescent state of
      these cells in the nerves of normal mice.

PMID- 8269864
TI  - Postnatal neuron death in the nodose ganglia of the rat.
AB  - Developmental neuron death is well described in sensory and sympathetic ganglia
      derived from the neural crest. In this study, nodose ganglia were removed from 2
      litters of postnatal rats (male and female; 1, 3, 5, 9, and 14 days old) in order
      to determine whether postnatal neuron degeneration occurs in the nodose ganglia,
      which is derived from ectodermal placode. The ganglia were embedded in paraffin,
      sectioned and stained with methylene blue. Neuronal nuclei were counted at a
      magnification of 100 and diameters of nodose nuclei were traced at each age.
      There was a significant (p < 0.001) increase in the nuclear diameter of the
      nodose neurons of male and female rats from birth to postnatal day 14. In male
      rats, this difference was most marked between postnatal day 5 and postnatal day
      14. The results of the neuron counts for both male and female rats indicated a
      gradual, significant (p < 0.001) decrease in the neuron population from day 1 to
      14. For the males a 57.2% decline was observed, while the females displayed a
      49.2% decline. The numbers of neurons in male and female ganglia showed no
      consistent differences. The data for neuron counts suggest that developmental
      neuron death occurs in postnatal rats with a gradual decrease in number of nodose
      neurons. However, since our findings show no evidence of degenerating nodose
      neurons, we are unable to rule out the possibility of migration from the
      developing ganglion.

PMID- 8269865
TI  - Erythrocyte band 3-like protein immunoreactivity in the human brain cortex.
AB  - The immunoreactivity of erythrocyte band 3 (B3-IR)-related protein was estimated
      on cortex biopsies from the brains of 33 patients varying in age from 14-week-old
      fetus until 67 years of life. B3-IR was not a feature of embryonic brains. A
      positive reaction was restricted to neurons. It appeared at early postnatal life,
      increased sharply until 9 years, and than stayed approximately stable between 17
      and 67 years of age. The results indicate that there is a positive relation
      between the amount of neuronal band 3-like protein and the stage of human brain
      development.

PMID- 8269866
TI  - Jimpy mutation affects astrocytes: lengthening of the cell cycle in vitro.
AB  - The jimpy mutation has been identified as a point mutation in the gene coding for
      the major myelin proteolipid protein. The most prominent effect of the mutation
      is an extreme reduction in central nervous system myelin in affected mice.
      However, both oligodendrocytes and astrocytes, the two types of central nervous
      system macroglia, have been shown to exhibit more subtle developmental and
      metabolic changes as a result of the mutation. These include early death and
      proliferation abnormalities in jimpy oligodendrocytes, and hypertrophy, increased
      pH and abnormal responses to high K+ in jimpy astrocytes. In the present study,
      we examine the effect of the mutation of the cell cycle of astrocytes. Using an
      immunocytochemical method to chart the percent of labeled mitoses, we find the
      total cell cycle to be lengthened in jimpy astrocytes by 5-6 h, with increases in
      several different phases. Since there is no evidence that astrocytes make myelin
      proteolipid protein, the results support previous studies which suggest that this
      gene may code for other proteins playing an important role in the development of
      many cell types.

PMID- 8269867
TI  - Regulation of neuronal differentiation by retinoic acid alone and in cooperation
      with thyroid hormone or hydrocortisone.
AB  - Cultures highly enriched in neurons obtained from embryonic mouse cerebra were
      used to demonstrate that: (1) at the optimum concentration of 10(-8) M retinoic
      acid stimulated the neurons to produce axon- and dendrite-like structures as
      determined by phase contrast and fluorescent microscopy; (2) the same
      concentration of retinoic acid stimulated acetyl cholinesterase and choline
      acetyltransferase activities; (3) treatment of neurons of either prenatal or
      neonatal equivalent age with retinoic acid produced a sustained stimulation of
      neuronal differentiation, and (4) retinoic acid cooperatively stimulated neuronal
      differentiation with either thyroid hormone or hydrocortisone.

PMID- 8269868
TI  - Laminar analysis of the number of neurons, astrocytes, oligodendrocytes and
      microglia in the visual cortex (area 17) of 6- and 12-month-old rhesus monkeys
      fed a human infant soy-protein formula with or without taurine supplementation
      from birth.
AB  - The effect of taurine supplementation of a commercial (taurine-free) soy protein
      formula on the development of the visual cortex has been examined in 6- and 12
      month-old rhesus monkeys. The thickness, numerical density and total number of
      neurons, oligodendrocytes, astrocytes and microglia have been measured in the
      different laminae. There was no difference in brain weight at either age. The
      thickness of layers I and VI were greater in the taurine-deprived (-T) monkeys at
      12 months than in the taurine-supplemented (+T) monkeys. There was no difference
      in any measure of neurons at 6 or 12 months between the +T and -T groups, but
      there were several differences in the measures of glial cells. Somewhat
      surprisingly, monkeys fed the taurine-free formula for 6 months followed by the
      taurine-supplemented formula for 6 months (reversal group, -T/+T) had a number of
      differences from the other 12-month groups in measures of both neurons and glial
      cells. These results add to our previous data indicating that there are
      significant disadvantages to primates fed a taurine-fed formula during
      development.

PMID- 8269869
TI  - Facial palsy: a neglected affliction.

PMID- 8269870
TI  - Facial nerve neuroma.

PMID- 8269871
TI  - Endoscopic view of the inferior turbinate.

PMID- 8269872
TI  - Vocal fold paralysis and bilateral vocal fold hemorrhage.

PMID- 8269873
TI  - Anastomosis of the intratemporal facial nerve using fibrin tissue adhesive.
AB  - This work aimed at studying the results obtained by the repair of complete
      lesions of the facial nerve in its intratemporal portions. Clinical,
      electrophysiological and surgical techniques were studied. Twenty-three patients
      with traumatic facial nerve lesions were operated. Nerve grafts were made in 10,
      and end-to-end anastomosis in thirteen. The surgical technique performed was the
      coaptation of the stumps and stabilization with fibrin tissue adhesive. Sixteen
      months after surgery, a clinical and electrophysiological evaluation was made.
      The use of fibrin tissue adhesive to stabilize intratemporal anastomosis of
      facial nerve showed clinical and electrophysiological evidence of axonal growth
      and reinnervation of mimical muscles of the face. These results were similar to
      that obtained by other authors that used other methods of microanastomosis. The
      use of fibrin tissue adhesive is an effective technique to utilize in
      intratemporal anastomosis of the facial nerve.

PMID- 8269874
TI  - The facial nerve: how to find it.
AB  - Iatrogenic facial paralysis is one of the most serious and most dreaded
      complications of temporal bone surgery. The risk of this complication as well as
      the duration of surgery can be reduced if the otologic surgeon can promptly
      identify the facial nerve at any stage of an operation. This is especially
      important in cases of anatomic variation and pathology which obscures or distorts
      normal anatomy. Twelve different surgical techniques will be described which
      allow the surgeon to safely expose and identify the facial nerve throughout its
      course through the temporal bone at any stage of an operation.

PMID- 8269875
TI  - Eyelid reanimation with the palpebral spring after facial nerve graft surgery: an
      interdisciplinary approach.

PMID- 8269877
TI  - Nasal signs and symptoms of the allergic response--perennial rhinitis.

PMID- 8269876
TI  - Surgical management of the paralyzed eyelid.
AB  - The most devastating sequelae of the facial nerve paralysis is the loss of eyelid
      function. The inability to blink, lubricate and protect the globe can lead to
      exposure keratitis, corneal abrasion and even the loss of vision. Eyelid closure
      is approximately 85% upper eyelid and 15% lower eyelid. In order to ensure
      adequate protection of the globe, deficiencies of both eyelids must be addressed.
      We report our experience with 20 patients with eyelid paralysis. Upper lid
      reanimation was performed by the placement of gold lid weights on the tarsal
      plate. Lower lid reanimation procedures included lateral canthopexy and
      horizontal lid shortening. A discussion of the above-mentioned procedures, the
      timing of the procedures and a critical analysis of results will be included. A
      comprehensive approach to the management of the paralyzed eye will be presented.

PMID- 8269879
TI  - Variations in stroke rate and loading using hand sonic or ultrasonic
      instrumentation.
AB  - An in vitro model system was developed to investigate the stroke rate and loading
      during hand, sonic, or ultrasonic instrumentation. The model system consisted of
      a mandibular molar tooth attached to a strain gauge and interface to a computer.
      Ten clinicians instrumented the distal canal of lower molar teeth. Stroke rates
      used and loads applied were measured using different sized files with the three
      different preparation techniques. There was no significant difference in stroke
      rates between different file sizes (p > 0.05) within the same generator, however,
      stroke rate for hand was significantly slower than for sonic or ultrasonic (p <
      0.01). Loading of the canal wall rose with increase in file size which was
      significant for hand (p < 0.01) and sonic (p < 0.05) but not ultrasonic (p >
      0.05). There was a tendency for loading to be higher with hand instrumentation,
      this however was not significant (p > 0.05).

PMID- 8269878
TI  - Resin restorations: leakage, bacteria, pulp.
AB  - Through the development of composite resin materials, the acid-etch technique and
      dentin adhesives, dentists can now complete perfect and permanent dental
      restorations--restorations with a color and shape approximating the natural
      tooth, with perfect marginal adaptation, and no harmful effects to the
      surrounding tissues, including the dental pulp. However, newer cross-sectional
      studies indicate that marginal defects are still the main cause of replacement of
      resin restorations, and that their clinical durability is shorter than that of
      other types. Moreover, there is no doubt that gap preventive treatments can
      intensify pulpal reactions to resin restorations if bacterial leakage occurs. The
      present thesis is based on nine previously published studies (I-IX). The aims of
      the studies were: to examine the possibilities of minimizing the occurrence of
      bacterial leakage around resin restorations through the use of various gap
      preventive procedures, to extend our understanding of their mode of action, and
      to investigate the pulpal reactions associated with restorations with and without
      bacterial leakage. The results of earlier research are reviewed, as well as the
      various methods for registration of gap occurrence around restorations. Studies I
      IX are described briefly and followed by a discussion of the results, a summary
      and some concluding remarks.

PMID- 8269880
TI  - Treatment of root-fractured maxillary incisor with Thermafil obturator.
AB  - This case report describes the treatment of a maxillary left central incisor with
      intra-alveolar horizontal root fracture in the middle of the root. The pulp of
      the coronal segment was necrotic and endodontic treatment was performed.
      Instrumentation of the root canal through the fracture line was carried out and
      the tooth was obturated with Thermafil in order to bring about a union of the
      fragments. At the 24-month follow up examination the tooth was functionally and
      esthetically normal. Radiographically no pathosis was evident in the periapical
      or fracture areas.

PMID- 8269881
TI  - Evaluation of the dimensional stability of different thermoplasticized gutta
      percha fillings using simulated glass root canals.
AB  - The dimensional stability of different thermoplasticized gutta-percha fillings
      was analyzed using simulated glass canals. For comparison, gutta-percha fillings
      obtained with the cold lateral condensation technique was used. The evaluation
      was done at 0 min, 2 min, 5 min, and 30 min after the filling was completed. The
      general analysis showed statistically significant differences between 0 min and 5
      min-30 min recordings. No significant differences were found between 0 min and 2
      min, and between 2 min, 5 min, and 30 min. Although warm lateral condensation
      resulted in a poor obturation, it was the only thermoplasticized technique
      analyzed that did not produce significant volumetric changes between 0 min and 30
      min. All the other thermoplasticized filling techniques showed important
      shrinkage during cooling.

PMID- 8269882
TI  - Bio-microscopical observation of dystrophic calcification induced by calcium
      hydroxide.
AB  - Calcium hydroxide paste was introduced into a rabbit ear chamber, and the effect
      of calcium hydroxide on the vascular tissue was observed under a bio-microscope
      continuously up to 14 weeks. Many precipitates were observed at the border of
      living tissue, after the dissolution of microvessels around the paste. They
      increased both in size and number to combine like a river bank in the first 48 h.
      After 1 week, microcirculation recovered, and newly-formed capillaries approached
      the precipitate-bank, the edge of which became smoother as weeks went by. The
      bank was stable and compatible to microvessels during the observation period. By
      SEM observation, the width of the bank was from 200 to 400 microns, and the
      tissue-side of the bank appeared like amorphous lamellae, while the inner-side
      showed particle-like appearance. EDX examination revealed high peaks of Ca and P
      similar to calcium phosphate at the tissue-side of the bank, but only Ca peak at
      the inner-side. The precipitates seemed to have the potential to induce
      dystrophic calcification by absorbing Ca and P from the tissue.

PMID- 8269883
TI  - Partial pulpotomy in crown-fractured permanent incisor with hyperplastic
      pulpitis: a case report.
AB  - Hyperplastic pulpitis, which is regarded as one type of asymptomatic irreversible
      pulpitis, occurs usually in young teeth where pulps are exposed by caries or
      trauma. If apices are mature, root canal therapy is recommended. In this case,
      the success of partial pulpotomy in a crown-fractured permanent incisor with
      hyperplastic pulpitis, which had been contaminated with oral microflora for six
      months is reported.

PMID- 8269884
TI  - Dietary lectins are metabolic signals for the gut and modulate immune and hormone
      functions.
AB  - Although it is common knowledge that some dietary lectins can adversely affect
      the growth and health of young animals and that, therefore, lectins are
      implicated in nutritional disorders of the digestive system, it has not been
      rigorously established that findings with animals are also directly applicable to
      humans. However, because the glycosylation state of the human gut is basically
      similar to that of higher animals, it may be confidently predicted that the
      effects of dietary lectins will have similarities in both humans and animals. The
      more recent but not generally appreciated realization that lectins also have many
      beneficial effects on the gut and metabolism of animals makes the exploration of
      these for possible use in medical-clinical practice even more attractive. Most
      lectins in our diet are resistant to breakdown during gut passage and are bound
      and endocytosed by epithelial cells. These lectins are powerful exogenous growth
      factors for the small intestine, can induce dramatic shifts in its bacterial
      flora and interfere with its hormone secretion. In addition, lectins which are
      transported across the gut wall into the systemic circulation can modulate the
      body's hormone balance, metabolism and health. Although these physiological
      effects are mediated or reinforced by immune responses, they are primarily the
      result of the specific chemical reactivity of lectins with cell surface receptors
      of the gut. Clearly, as the interactions between lectins and the gut are
      predictable and may be manipulated to our advantage, the exciting scientific
      challenge is now to explore the possible transfer of the existing knowledge
      gained from animal experimentation to medical-clinical practice.

PMID- 8269885
TI  - Increase in serum selenium levels in Finnish children and young adults during
      1980-1986: a correlation between the serum levels and the estimated intake.
AB  - Serum selenium concentrations of Finnish children and adolescents (ages: 3, 6, 9,
      12, 15 and 18 years) were analysed in 1980. The sample included 1706 subjects
      from five different areas, each containing rural and urban sectors. The serum
      selenium concentration levels were compared to the intakes of energy, selenium,
      protein, fat and carbohydrate estimated by a dietary survey (in a total of 1090
      subjects from the 1706). In 1986 corresponding data were obtained from 280 of the
      subjects from the 1980 sample. The mean intake of selenium from food in 1980
      ranged from 12 to 23 micrograms per day for the different age groups. In 1986,
      after the addition of selenium to fertilizers, the mean daily intake of selenium
      ranged from 69 to 82 micrograms per day for the groups of subjects, who were 9,
      12, 15, 18, 21 and 24 years old by that time. In 1980, the children aged 3 and 6
      years had lower selenium concentrations in their sera compared to the other age
      groups. However, serum selenium levels were higher in the Tampere and Oulu areas.
      In 1986 the selenium concentrations in sera increased with age (9-21-year-olds)
      and no regional differences were found. The selenium levels in sera were higher
      in 1986 than in 1980 due to the increased intake after the addition of selenium
      to fertilizers used in Finland. The increase in selenium levels between the 1980
      and 1986 studies were, on the average, 45%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8269886
TI  - Increasing calcium intake in women on a low-fat diet.
AB  - Dietary advice to reduce the risk of coronary heart disease (CHD) is aimed at
      reducing saturated fat intake, especially in people with hyperlipidaemia. Dairy
      products contribute a considerable proportion of the fat intake of many people's
      diet in New Zealand, and are thus often reduced. However, dairy products provide
      about 60% of the dietary calcium. This study investigated the calcium intake of
      50 women aged 40-65 years on fat-reduced diets. The effect of giving standardized
      information on the importance of calcium intake, and on ways to increase this,
      was assessed by a repeat dietary analysis 3 months later. The mean (SD) calcium
      intake was initially 696 (245) mg per day; below that recommended for post
      menopausal women. The mean percentage energy from fat and saturated fat was 28.5%
      and 9.6%, respectively. Three months later, after the specific advice on calcium,
      the mean calcium intake was significantly higher at 938 (317) mg per day, with
      88% having increased their intake, yet the intake of energy, fat and saturated
      fat were unchanged. This was mainly achieved by increased use of low-fat dairy
      products. Specific advice about calcium should be given to women commencing lipid
      lowering diets in order to attain recommended intakes and to reduce the risk of
      osteoporosis, as well as CHD.

PMID- 8269887
TI  - Basal metabolic rate in human subjects migrating between tropical and temperate
      regions: a longitudinal study and review of previous work.
AB  - A review of the studies of basal metabolic rate (BMR) in human subjects migrating
      between tropical and temperate countries is presented. Such an analysis showed
      conflicting results of BMR in tropical migrants when expressed as BMR/kg/d. Much
      of this confusion may be attributable to experimental design and poor selection
      of subjects. A longitudinal study of BMR in 18-30-year-old males migrating for
      the first time from a tropical to a temperate country (the UK) was undertaken to
      address disparities seen in the earlier reviewed work. BMR was measured in
      tropical migrants and their temperate resident peers serially from 2 to 3 weeks
      post-migration to up to 6 months later, making advances on previous studies which
      did not measure BMR so promptly post-migration, or conduct serial measurements.
      The tropical migrants recruited in this investigation were of high socioeconomic
      status and well nourished. BMR/kg/d was similar in tropical migrants and
      temperate residents, there being no time trend in either group through the course
      of the study. The BMR of both groups was similar to that of populations born and
      resident in temperate regions, in contrast to the lower BMRs of born and resident
      tropical peoples reported in the literature. It is suggested that these lower
      BMRs are the result of a different relationship of BMR with body weight in
      individuals who are undernourished and/or of low socio-economic status, the
      corollary of which is a lower body weight, stature and body mass index.

PMID- 8269888
TI  - Consumer estimates of the percentage energy from fat in common foods.
AB  - Two-hundred and ninety-three UK consumers completed a questionnaire eliciting
      estimates of fat content (as a percentage of energy) of 24 common foods, along
      with information on respondents' nutrition training, perceived knowledge and use
      of nutrition information, age, sex, height, weight, and eating restraint. The
      relative positioning of foods with regard to fat content was generally correct;
      however, there was a consistent tendency to overestimate the fat content of foods
      low in fat and to underestimate those high in fat. Estimates of fat content were
      characterized by wide deviations from true values, and were particularly poor for
      several specific foods. Females and respondents with formal (but not informal)
      nutrition training were more accurate overall, but still made large errors in
      estimate for certain food items. The results indicate that many consumers are
      likely to have substantial misconceptions regarding the relative proportion of
      energy derived from fat in many common foods.

PMID- 8269889
TI  - Can bioelectrical impedance improve the prediction of body fat in patients with
      eating disorders?
AB  - Prediction equations for percentage body fat have been derived for a group of 93
      female patients being treated for eating disorders, using fat measured by dual
      energy X-ray absorptiometry (DXA) as the reference method. Separate bioelectrical
      impedance analysis (BIA) prediction equations were derived for patients with a
      body mass index above and below 16 kg/m2. This provided an improvement compared
      with the equations supplied by the manufacturer. The standard error of the
      estimate (SEE) for the entire group was 3.2% (r = 0.922). However, an alternative
      prediction equation based on anthropometry alone gave an SEE of 4.2% (r = 0.861).
      The ability of BIA and anthropometry alone to measure changes in percentage fat
      was assessed in a separate group of 24 females during treatment for eating
      disorders. The SEEs using the BIA and anthropometry prediction equations were
      2.6% (r = 0.931) and 2.7% (r = 0.901) respectively. We conclude that in patients
      with eating disorders BIA does not provide any significant improvement over
      simple anthropometry prediction equations for the assessment of percentage fat or
      its changes. The apparently reasonable agreement between fat predicted by BIA and
      that measured by DXA is largely due to the inclusion of body habitus parameters
      in the BIA prediction equations.

PMID- 8269891
TI  - Changing patterns of fat intake in Mediterranean countries. Seminar, Barcelona, 1
      3 June 1992. Proceedings.

PMID- 8269890
TI  - Effect of a strict vegan diet on energy and nutrient intakes by Finnish
      rheumatoid patients.
AB  - Dietary intake data of 43 Finnish rheumatoid arthritis patients were collected
      using 7-day food records. The subjects were randomized into a control and a vegan
      diet groups, consisting of 22 and 21 subjects, respectively. The subjects in the
      vegan diet group received an uncooked vegan diet ('living food') for 3 months,
      and they were tutored daily by a living-food expert. The subjects in the control
      group continued their usual diets and received no tutoring. Adherence to the
      strict vegan diet was assessed on the basis of urinary sodium excretion and by
      the information on consumption of specific food items (wheatgrass juice and the
      rejuvelac drink). The use of these drinks was variable, and some boiled
      vegetables were consumed occasionally. However, only one of the subjects in the
      vegan diet group lacked a clear decrease in urinary sodium excretion. Rheumatoid
      patients had lower than recommended intakes of iron, zinc and niacin, and their
      energy intake was low compared to mean daily energy intake of the healthy Finnish
      females of the same age. Shifting to the uncooked vegan diet significantly
      increased the intakes of energy and many nutrients. In spite of the increased
      energy intake, the group on the vegan diet lost 9% of their body weight during
      the intervention period, indicating a low availability of energy from the vegan
      diet.

PMID- 8269892
TI  - Nutrition in the health policy context of Catalonia. Introduction.

PMID- 8269893
TI  - Changing patterns of fat consumption in Spain.
AB  - Trends of fat and fat-containing food consumption in Spain are analysed;
      information was obtained from data collected at two different levels: household
      and individual. Three major household budget surveys conducted by the National
      Institute of Statistics in 1964, 1980-1981, and 1990-1991 show the trends of food
      and fat consumption in Spain; we can observe a decrease in cereals, potatoes and
      pulses and an increase in dairy products and meat, similar to that observed in
      other countries. According to these studies, the consumption of fat and saturated
      fat and the other vegetable oils have increased, while olive oil intake has
      decreased. Food and fat consumption in Spain presents a large variation between
      the Spanish regions. Six individual dietary studies conducted among adult free
      living populations are reviewed; intakes of fat ranged from 90 to 110
      g/person/day, and percentage of total energy from saturated fat from 12 to 15%.
      The rise in fat intake in Spain urges dietary interventions.

PMID- 8269894
TI  - Changing patterns of fat intake in Crete.

PMID- 8269895
TI  - Changes in diet and mortality from selected cancers in southern Mediterranean
      countries, 1960-1989.
AB  - Mortality trends of breast, colorectal, ovarian and prostate cancer in Spain,
      Italy, Greece, Yugoslavia, and England and Wales are presented. Figures are
      discussed with regard to patterns of consumption of fat-containing foods in these
      countries. An increase of all cancer site mortality is shown in southern European
      countries, whereas in England and Wales a decrease in ovarian and colorectal
      cancer among women is observed. Consumption of milk, meat and animal fat products
      increased in all Mediterranean countries but decreased in England and Wales. Some
      differences regarding cancer mortality and food consumption patterns among
      southern European countries are pointed out. This markedly divergent fat
      consumption pattern between northern and southern Europe appears to antedate and
      be associated with their substantial differences in ovarian and colorectal cancer
      mortality trends, and to a lesser extent with breast cancer.

PMID- 8269896
TI  - Dietary fat and cancer in Italy.

PMID- 8269897
TI  - Assessment of fat intake in retrospective epidemiological studies.
AB  - The evidence on the positive association between fat intake and the risk of
      several cancers, including cancer of the breast, digestive tract and female
      genital tract, is substantial. Further, the interpretation of some null
      associations is hampered by various difficulties in the evaluation of the fat and
      cancer link.

PMID- 8269898
TI  - Trends in fat consumption in Europe and their influence on the Mediterranean
      diet.

PMID- 8269899
TI  - Cardiovascular mortality trends in Spain and Catalonia. Comparisons with Europe.
AB  - Cardiovascular mortality trends in Spain during the last 15 years have been
      reviewed and compared with those observed in other European countries. Future
      coronary heart disease (CHD) mortality trends in Catalonia have been estimated,
      and its expected evolution with intervention programmes on the prevalence of
      hypercholesterolaemia is discussed. The main conclusions are: (a) a reduction in
      stroke and no changes in CHD mortality in Spain and Catalonia has been observed
      during recent years; (b) this evolution was similar to that observed in other
      European countries; (c) Spain, like other Mediterranean countries, shows a
      peculiar cardiovascular mortality pattern with predominance of stroke over CHD;
      (d) no spectacular changes in CHD mortality trends during the next few years can
      be expected in Catalonia, but reductions in the prevalence of
      hypercholesterolaemia may contribute to modify the stable CHD mortality trends.

PMID- 8269900
TI  - Hypercholesterolaemia in childhood: repercussions in adulthood.
AB  - The development of atherosclerotic vascular disease is influenced by multiple
      factors present since early age. Abnormal lipid metabolism, a major cause of
      atherosclerosis, results from genetic predisposition and is influenced by a
      variety of exogenous conditions. This article reviews the published studies of
      serum cholesterol tracking. The Sherbrooke cohort study on serum cholesterol
      tracking from early infancy to adolescence is described. The role of dietary
      habits, nutrient intake and other lifestyle-associated factors are scrutinized.
      Finally, a family-oriented detection of coronary risk factors in adolescence is
      discussed with emphasis on the future implementation of new genetic techniques.

PMID- 8269901
TI  - The use of fats and oils by the food industry.

PMID- 8269902
TI  - Isomeric trans fatty acids in the Spanish diet and their relationships with
      changes in fat intake patterns.
AB  - Eleven different groups of food products (total samples 378), representing about
      90% of total fat intake in Spanish diet, were analysed by gas chromatography in
      order to determine their contents and variability of trans fatty acids. With
      official data of food consumption in Spain, trans fatty acid intake is calculated
      for recent decades and results are compared with data available from other
      countries. Mean intake in Spain obtained from this calculation is 2.4
      g/person/day. This is lower than values for other food consumption models in
      which the major fats are of animal origin or industrially processed.

PMID- 8269903
TI  - Fat and alcohol intake in the Basque Country.
AB  - A cross-sectional nutritional survey was carried out in the Basque Country, on a
      random sample of the population aged 25-60 years (n = 2348). Socioeconomic data,
      anthropometric measurements and food consumption data were collected. 24-h recall
      on three non-consecutive days plus a food frequency questionnaire were used for
      dietary assessment. The participation rate was 73.4%. Mean energy intake for men
      was 2944 kcal and 2049 kcal for women, decreasing with age. Energy distribution
      pattern (non-alcohol) showed 16% from protein; 38% from fat: 13% SFA; 16% MUFA
      and 9% PUFA; carbohydrates supplied 46% energy. Alcohol intake was 8%. Better
      educated people had higher intakes of SFA, cholesterol and sugar (P < 0.001).
      Consumption of meat (162 g/person/d) and fish (89 person/d) were high. Cereals
      and potatoes were the main sources of energy in the Basque diet (23.24%) followed
      by meat, fish and eggs (20%). Percentage contribution to energy intake from meat
      was higher in men than in women, and also energy intake from alcohol. Women
      obtain more energy from milk. Edible fat was the main source of fat in the diet
      (46%) followed by meat (22%). Milk products and meat are the main sources of SFA
      in the Basque diet. Males had a high intake of alcohol, especially in the 35-44
      year age group. Alcohol consumers usually drink every day and often not in the
      home.

PMID- 8269904
TI  - Does nut consumption protect against ischaemic heart disease?
AB  - Nuts are part of the Mediterranean tradition. For millennia, tree nuts have been
      in the region. Results of an epidemiological study conducted among California
      Adventists provide strong evidence that frequent consumption of nuts have a
      protective effect on both fatal and non-fatal ischaemic heart disease events. The
      unique nutrient composition of nuts makes it plausible that nuts favourably
      affect heart disease risk factors and interfere with the process of
      atherogenesis. Results of recently conducted human nutritional studies, with
      varying degrees of methodological rigour, all seem to indicate that eating nuts
      lowers serum cholesterol and favourably modifies the lipoprotein profile. The
      effects of nut consumption on other cardiovascular disease risk factors deserve
      further exploration.

PMID- 8269905
TI  - The traditional Greek diet.
AB  - Data from several studies are presented which suggest that the traditional Greek
      diet still exists in several parts of Greece and several segments of the
      population. The most profound changes in dietary intakes in recent years concern
      the increase in the consumption of meat and the decrease in the consumption of
      pulses.

PMID- 8269906
TI  - Recent findings in olive oil research.

PMID- 8269907
TI  - Fish consumption, omega-3 fatty acids and the Mediterranean diet.
AB  - Many epidemiological, interventional and animal studies have concluded that
      consumption of polyunsaturated fatty acids of marine origin may confer special
      benefits in reducing cardiovascular heart disease (CHD) mortality rates by
      different physiological mechanisms. The available epidemiological data, although
      limited, suggest that a dietetic recommendation on the consumption of one or two
      servings per week (200-300 g = 2-4 g eicosapentaenoic acid) of cold water marine
      fish could lead to a reduction of the CHD risk. Nevertheless, there are important
      methodological shortcomings and contradictory findings in most published
      investigations on the omega-3 fatty acids. In order to assess the role of fish
      consumption in the Mediterranean diet, we have compared data on average fish and
      fatty fish consumption trends in some Mediterranean (Spain, Yugoslavia and Italy)
      and northern European (Norway, Denmark) countries. Fish consumption is not
      positively correlated with ischaemic heart disease mortality. That suggests that
      dietary factors other than fish, such as the lower meat consumption associated to
      the higher fish intake, or other differences of lifestyle have perhaps
      intervened, helping to explain the healthy nature of the Mediterranean diet.

PMID- 8269908
TI  - Social marketing and fat intake.

PMID- 8269909
TI  - The future of nutrition in Europe.
AB  - The availability of food and the nutritional status of western Europeans have
      never been so good as in recent decades. However, we have not to go back too long
      to see that severe malnutrition also occurred in parts of western Europe. An
      example was the malnutrition and starvation causing high death rates in the
      western Netherlands in the early months of 1945, just before the end of the
      Second World War. Today there is an abundance of food in western Europe.
      Nevertheless we do warn people that the food, nutritious and delicious as it is,
      may be hazardous to health. Degenerative diseases like cardiovascular diseases,
      cancer, diabetes, obesity, osteoporosis and hypertension are very prevalent in
      our society. It is very likely that certain nutrients in foods do contribute both
      to the causes and prevention of these diseases. In this paper some new findings
      of the role of diet in health will be reviewed. This will be followed by a brief
      discussion on the status of nutrition research and training in Europe. Finally
      attention is asked for the need to start building-up a programme for nutritional
      leadership in Europe.

PMID- 8269910
TI  - Frequency-dependent enhancement of hippocampal inhibition by GABA uptake
      blockers.
AB  - The effects of GABA uptake inhibitors, SKF 89976A and SKF 100330A, on recurrent
      inhibition were studied in the rat hippocampal slice preparation by the
      antidromic-orthodromic stimulation test. Population spikes evoked orthodromically
      by stimulation of the stratum radiatum and recorded in the CA1 pyramidal cell
      body layer were inhibited antidromically by stimulation of the alveus by a single
      pulse or by a train of pulses, either at low or at high frequency. Low frequency
      train conditioning produced less inhibition than a single pulse. The uptake
      blockers had no effect or slightly enhanced the inhibition produced by single
      stimuli or low frequency trains. High frequency train conditioning produced more
      and much longer inhibition than a single pulse. This inhibition was further
      substantially enhanced and prolonged by the drugs. Frequency-dependent
      enhancement of inhibition may be responsible for suppression of epileptiform
      discharges by GABA uptake blockers.

PMID- 8269911
TI  - The role of technical, biological, and pharmacological factors in the laboratory
      evaluation of anticonvulsant drugs. V. Lack of seasonal influences on amygdala
      kindling in rats.
AB  - Previous studies have suggested that seizure models may be affected by seasonal
      rhythms, even under controlled environmental conditions. In the present
      experiments in rats with chronically implanted electrodes in the basolateral
      amygdala, kindling was initiated at different seasons of the year over a period
      of 3 years. In a total of 109 animals, the following parameters were determined:
      the threshold for induction of amygdaloid afterdischarges prior to kindling (pre
      kindling ADT), the number of daily amygdaloid stimulations to fully kindled
      (stage 5) seizures, and the post-kindling ADT. No seasonal influences were found
      with respect to rate of kindling development and post-kindling ADT. In contrast,
      pre-kindling ADTs appeared to be higher in spring than in other seasons, which,
      however, could not be reproduced in another spring. Thus, the data do not
      indicate that seasonal rhythms affect the kindling model of epilepsy.

PMID- 8269912
TI  - Epileptic focus induced by intrahippocampal cholera toxin in rat: time course and
      properties in vivo and in vitro.
AB  - A small dose (0.5-1.0 micrograms) of cholera toxin injected into rat hippocampus
      induced an epileptic focus which discharged intermittently for 7-10 days.
      Epileptic discharges lasting from 70 ms to 2 min were recorded in vivo through
      implanted electrodes. The longer bursts could generalize to the neocortex, and
      occasionally caused motor seizures. The epileptic bursts reached a maximum 3-4
      days after injection, and then declined to occasional brief interictal discharges
      by 9 days. Postmortem histology revealed no evidence of gross pathology or
      neuronal loss. Hippocampal slices prepared from rats < 8 days after injection of
      cholera toxin, and maintained in vitro, generated brief spontaneous and evoked
      epileptic bursts, usually lasting < 1 s. Spontaneous bursts always started in
      subregion CA3c, and propagated through the pyramidal layer at a mean of 0.18 m/s.
      Intracellular recordings from CA3 pyramidal layer cells always revealed
      simultaneous paroxysmal depolarization shifts during epileptic bursts. Epileptic
      activity, both in vivo and in vitro, required the whole toxin molecule.
      Injections of either the B subunit or the vehicle solution were not
      epileptogenic. Therefore binding of the toxin to neuronal membranes, which is
      mediated by the B subunit, was not sufficient for the epileptogenic effects of
      cholera toxin. This suggested that the activation of Gs which requires the whole
      molecule, was necessary. Gs activation is known to stimulate cyclic AMP
      production, but forskolin, which directly stimulates adenyl cyclase, failed to
      produce epileptic activity, even though it depressed action potential
      accommodation and afterhyperpolarizations (AHPs). While further work is required
      to resolve the basic mechanisms of cholera toxin induced epileptic foci, we
      propose that they require the activation of Gs, which can enhance Ca2+ currents
      and modify excitatory synaptic transmission directly. Cyclic AMP induced changes
      in these properties cannot be excluded. However, cyclic AMP induced reductions in
      action potential accommodation and AHPs, which are found in cholera toxin foci,
      may contribute to, but are not sufficient for, epileptogenesis. Cholera toxin
      differs from the commonly used epileptic agents in that its main action is on G
      proteins and second messenger systems, rather than on synaptic transmission
      directly. Furthermore it has a prolonged time course, and does not cause gross
      pathology. These features combine to make it a distinctive model for epilepsy and
      neuronal synchronization.

PMID- 8269913
TI  - Carbamazepine and phenytoin in epilepsies refractory to barbiturates: efficacy,
      toxicity and mental function.
AB  - A group of 51 patients with chronic cryptogenic or symptomatic localized epilepsy
      refractory to therapy with barbiturates underwent progressive substitution with
      phenytoin or carbamazepine, in standardized and randomized fashion. After drug
      changes were completed two thirds of the patients remained seizure free during a
      period of 6 months. A clearer effect of phenytoin and carbamazepine was seen on
      secondary generalized than on partial seizures. The frequency of severe side
      effects decreased after the change to phenytoin and carbamazepine. The group on
      carbamazepine improved in immediate and late recall, and in immediate and late
      recognition of pictures. The group on phenytoin improved significantly in the
      Stroop test. Patients changed to phenytoin, but not those changed to
      carbamazepine, became significantly more aggressive, anxious and depressive than
      when on phenobarbital, as measured by subjective scales. The results indicate
      that patients should not be considered refractory to antiepileptic drug therapy
      while on barbiturates. Cognitive dysfunction and mood changes observed in
      epilepsy may be temporary and dependent on the presence of seizures and/or on use
      of barbiturates.

PMID- 8269914
TI  - Thiamine and folate treatment of chronic epileptic patients: a controlled study
      with the Wechsler IQ scale.
AB  - Seventy-two epileptic patients receiving phenytoin (PHT) alone or in combination
      with phenobarbital for more than 4 years were divided into four groups, the first
      taking two placebo tablets per day; the second folate (5 mg/day) and placebo; the
      third placebo and thiamine (50 mg/day); and the fourth both vitamins. The
      clinical trial lasted 6 months. At baseline assessment, 31% of the patients had
      subnormal blood thiamine levels and 30% had low folate. The vitamin deficiencies
      were independent phenomena. It was found that thiamine improved
      neuropsychological functions in both verbal and non-verbal IQ testing. In
      particular, higher scores were recorded on the block design, digit symbol,
      similarities and digit span subtests. Folate treatment was ineffective. These
      results indicate that, in epileptics chronically treated with PHT, thiamine
      improves neuropsychological functions, such as visuo-spatial analysis, visuo
      motor speed and verbal abstracting ability.

PMID- 8269915
TI  - The excitatory amino acid antagonist D-CPP-ene (SDZ EAA-494) in patients with
      epilepsy.
AB  - The amino acids L-glutamate and L-aspartate have been shown to be excitatory
      neurotransmitters in mammalian central nervous systems. Antagonists acting
      selectively at excitatory amino acid receptors have shown antiepileptic
      properties in several animal models. We report the results of the first
      therapeutic trial of the competitive NMDA antagonist, D-CPP-ene (SDZ EAA-494), in
      eight patients with intractable complex partial seizures. All patients withdrew
      prematurely because of side-effects, including poor concentration (8), sedation
      (7), ataxia (6), depression (3), dysarthria (2), amnesia (2) and unilateral
      choreo-athetosis in a patient with contralateral Sturge-Weber syndrome. Seizures
      were unchanged in four patients and worse in three. A further patient with
      apparent improvement in seizures in the first week developed complex partial
      status epilepticus on withdrawal of DCPP-ene. EEG on treatment (5) or in the
      immediate post-treatment period (2) showed slowing of background activity and, in
      five cases, an increase in epileptiform activity. Serum concentrations of DCPP
      ene were found to be unpredictable and higher than expected from pharmacokinetic
      data on normal subjects. There was no clear relationship between serum
      concentrations and the severity of side-effects. Preliminary experience with DCPP
      ene in patients with refractory partial seizures is not promising. Evaluation of
      related compounds is warranted.

PMID- 8269916
TI  - Alterations in both excitation and inhibition occur before the onset of seizure
      activity in the hippocampus.
AB  - Excitatory and inhibitory mechanisms have been implicated in the onset of
      seizures and as underlying kindling. In this study, changes in responses to
      single stimuli and paired pulse stimuli were used to monitor postsynaptic
      excitability before the onset of seizure activity in limbic circuits of urethane
      anesthetized rats. With sufficient stimulus intensity, a stimulus paradigm of
      seven pulses every second for 10 s led to seizure activity, as indicated by the
      appearance of maximal dentate activation, and afterdischarges. An increase in the
      evoked response was found in both CA1 and the dentate gyrus during stimulus
      trains to either CA3 or the angular bundle and there was the appearance of a
      polysynaptic response. There was an increase in paired pulse inhibition in the
      dentate gyrus and a decrease in paired pulse inhibition in the CA1 region during
      the stimulus protocol. Since repeated seizures and a number of pharmacological
      agents are known to alter the onset and duration of seizure activity, a
      relationship between the changes in excitability and the onset of the seizure
      activity was tested using MK-801, ketamine, bicuculline, diazepam, phenobarbital,
      baclofen and repeated seizures. Overall, alteration of the amplitude of the
      polysynaptic response in CA1 to angular bundle stimulation correlated best with
      the effects of the drugs and the seizures on the duration of maximal dentate
      activation.

PMID- 8269917
TI  - Overexpression of Desulfovibrio vulgaris Hildenborough cytochrome c553 in
      Desulfovibrio desulfuricans G200. Evidence of conformational heterogeneity in the
      oxidized protein by NMR.
AB  - Plasmid pRC41, containing the cyf gene encoding cytochrome c533 from
      Desulfovibrio vulgaris Hildenborough, was transferred by conjugation from
      Escherichia coli to Desulfovibrio desulfuricans G200. The structural properties
      of the purified protein were studied by one-dimensional and two-dimensional NMR.
      A heterogeneity in the folding of the cytochrome isolated from D. vulgaris
      Hildenborough and from D. desulfuricans G200 was observed for the oxidized from.
      Temperature, pH and salt-dependence studies indicated that the heterogeneity does
      not result from an intermediate in the protein unfolding process, but derives
      from two conformations which are not in dynamic equilibrium.

PMID- 8269918
TI  - Complexes of the polyamines spermine, spermidine and putrescine with alpha
      lactalbumins.
AB  - The effects of polyamines on the spectral properties and thermal stability of
      different alpha-lactalbumins were measured. Addition of millimolar concentrations
      of spermine to the Ca(2+)-free (apo) form of bovine or goat alpha-lactalbumin
      resulted in spectral shifts, in both the far- and near-ultraviolet ranges,
      similar to those induced by Ca2+ binding. Fluorescence emission spectra of
      tryptophan residues underwent a pronounced blue shift, concomitant with a
      decrease in quantum yield. Also, in the presence of spermine, thermal stability
      was increased. In contrast, in the case of human and to some extent also equine
      alpha-lactalbumin, the shifts of the CD and fluorescence spectra and the thermal
      denaturation curves were in the opposite direction. Direct competition of
      spermine with Mn2+ could be observed for binding to the Ca2+ site of bovine alpha
      lactalbumin. As the main binding mode of spermine showed a 1:1 stoichiometry [K1
      = (2 +/- 0.5) x 10(4) M-1], we have assumed that binding occurs primarily at this
      site with one of the distal ammonium groups. In order to accommodate the
      remaining positively charged ammonium groups of spermine, a binding model was
      constructed by computer modeling, based on the atomic coordinates of both
      interacting species. This model makes use of the cluster of negatively charged
      glutamate residues present in the N-terminal sequence of bovine alpha
      lactalbumin, sterically close to the Ca2+ site. The spermine molecule could be
      nicely fitted in a space delineated by the Ca2+ site, on the one hand, and Glu1,
      Glu7 and Glu11, on the other. Our model, which has been extended to the shorter
      polyamines spermidine and putrescine, is able to fully account for the observed
      stabilization of bovine (and goat) alpha-lactalbumins against thermal
      denaturation, and for the observed CD and fluorescence spectral shifts. It also
      explains why human (and equine) alpha-lactalbumin behave differently.

PMID- 8269919
TI  - Human aldehyde dehydrogenase. cDNA cloning and primary structure of the enzyme
      that catalyzes dehydrogenation of 4-aminobutyraldehyde.
AB  - Human liver aldehyde dehydrogenase (E3 isozyme), with wide substrate specificity
      and low Km for 4-aminobutyraldehyde, was only recently characterized [Kurys, G.,
      Ambroziak, W. & Pietruszko, R. (1989) J. Biol. Chem. 264, 4715-4721] and in this
      study we report on its primary structure. Polyclonal antibodies, specific for the
      E3 isozyme and three oligonucleotide probes derived from amino acid sequence of
      the E3 protein, were used for isolation of the first cDNA clone encoding the
      human enzyme (1503 bp; coding for 440 amino acid residues). Additional clones
      were obtained by using the first isolated clone as a probe. The largest clone of
      1635 bp coded for 462 amino acid residues; it was longer at the 3'end of the cDNA
      non-coding region. The identity of the clone was established by DNA sequencing
      and by comparison with peptide sequences derived from the E3 protein, which
      constituted approximately 29% of the total primary structure of the E3 isozyme.
      The start codon was never encountered despite a variety of different approaches
      (500 amino acid residues were expected on the basis of SDS-gel molecular-mass
      determination of the E3 isozyme subunit). Despite the great catalytic similarity
      between the E3 and E1 isozymes [Ambroziak, W. & Pietruszko, R. (1991) J. Biol.
      Chem. 266, 13011-13018], the primary structure of the E3 isozyme has only
      approximately 40.6% of positional identity with that of the E1 isozyme. Sequence
      comparison with GenBank and Protein Identification Resource database sequences
      indicated no primary structure of aldehyde dehydrogenase more closely resembling
      the E3 isozyme than that of Escherichia coli betaine aldehyde dehydrogenase
      (52.7% positional identity), a prokaryotic enzyme specific for betaine aldehyde.

PMID- 8269920
TI  - Localization of the cross-linking site of GPRVVERHK in the gamma-chain of human
      fibrinogen.
AB  - The peptide alpha 17-24-Lys (GPRVVERHK) corresponding to the N-terminus of the
      alpha chain of fibrin was synthesized and used to localize its binding site in
      the fibrinogen molecule. The peptide was radioiodinated, incubated with
      fibrinogen, cross-linked with a bifunctional reagent disuccinimidyl suberate and
      the resulting product was analyzed in several ways, including plasmin digestion.
      The binding of the radioactive peptide was mainly to the gamma-chain and was
      inhibited by unlabelled GPRVVERHK and GPRP. After plasmin digestion, the
      radioactivity was present in fragment D1 and also in its gamma-chain remnant, but
      not in fragments D2, D3 or E3. Fragment D1 cross-linked with iodinated GPRVVERHK
      was purified by affinity chromatography on immobilized anti-fragment D IgG,
      further digested with plasmin in the presence of EGTA and the peptides were
      fractionated by reverse-phase HPLC. The amino acid sequence analysis of the
      radioactive peak revealed the presence of two peptides, gamma 357-373 and
      GPRVVERHK. It was concluded that the binding site for GPRVVERHK is in the
      sequence gamma 357-373 which is present in fragment D1 but absent in fragments D2
      and D3.

PMID- 8269921
TI  - Biosynthetic 15N and 13C isotope labelling of glutathione in the mixed disulfide
      with Escherichia coli glutaredoxin documented by sequence-specific NMR
      assignments.
AB  - A biosynthetic procedure for obtaining 13C-15N doubly labelled glutathione from
      readily available precursor molecules is described. Isolation of the mutant
      Escherichia coli [C14S]glutaredoxin from E. coli cultures grown on 15N-13C doubly
      labelled media in the absence of reducing agents yields the mixed disulfide
      labelled in both the protein and the glutathione. 15N NMR assignments for
      glutathione obtained from two-dimensional [15N,1H]-correlation spectroscopy
      (COSY), and 13C NMR assignments for the entire mixed disulfide obtained from
      combined use of three-dimensional ct-HA[CAN]HN experiments and HCCH-total
      correlation spectroscopy ([HCCH]-TOCSY) demonstrated unequivocally that the
      glutathione is uniformly labelled with both 15N and 13C. This result also
      supports earlier suggestions that the intracellular glutaredoxin activity is
      sensitive to the glutathione redox status of the cell. Complete sets of 1H, 13C
      and 15N chemical shifts of both components in the mixed disulfide of
      [C14S]glutaredoxin and glutathione were obtained from the sequence-specific NMR
      assignments.

PMID- 8269922
TI  - Conformation of thymosin beta 4 in water determined by NMR spectroscopy.
AB  - The conformational preferences of a 43-amino-acid G-actin-binding peptide,
      thymosin beta 4, in water at 1, 4 and 14 degrees C, and at pH 3.0 and 6.5 were
      studied by NMR. NMR showed that thymosin beta 4 lacks a uniquely folded
      conformation in water. However, some preferential alpha-helical conformations of
      thymosin beta 4 can be observed in aqueous solutions. The segment at residues 5
      16 showed characteristic interactions for conformations in both the beta-strand
      and alpha-helical regions of the phi-psi space, based on strong C alpha H(i)
      NH(i+1) interactions and NH-NH, C alpha H(i)-NH(i+3), and C alpha H(i)-C beta
      H(i+3) interactions, respectively. At 1-4 degrees C, another segment at residues
      31-37 also shows both beta and alpha conformations, forming however a less well
      defined helix than the segment at residues 5-16. At 14 degrees C, the
      conformational population of the helix at positions 5-16 is shifted more towards
      the random and turn-like structures, whereas the segment at positions 31-37
      becomes exclusively a random coil.

PMID- 8269923
TI  - 19F-NMR study on the pH-dependent regioselectivity and rate of the ortho
      hydroxylation of 3-fluorophenol by phenol hydroxylase from Trichosporon cutaneum.
      Implications for the reaction mechanism.
AB  - The regioselectivity and rate of the ortho-hydroxylation of 3-fluorophenol by
      phenol hydroxylase from Trichosporon cutaneum (EC 1.14.13.7) was studied using
      19F-NMR. The regioselective hydroxylation as well as the rate of ortho
      hydroxylation are pH dependent with a pKa of 6.5. At pH values below 6.5, 3
      fluorophenol preferentially becomes hydroxylated at the C6 ortho position,
      resulting in a maximum C6/C2 hydroxylation ratio of 6.7. Upon increasing the pH,
      the total rate of conversion increases. Also, the C2 ortho-hydroxylation
      increases relatively to the C6 ortho-hydroxylation and yields a minimum C6/C2
      hydroxylation ratio of 2.2 at pH values above 7.5. Based on data from 19F-NMR
      binding studies and molecular orbital calculations, a hypothesis is put forward
      which explains the pH-dependent effects observed. A mechanism is proposed
      involving an active-site amino acid residue acting as a base in the reduced form
      of the protein. Deprotonation of this residue results in hydrogen bond formation
      with the hydroxyl moiety of the phenolic substrate, leading to (partial)
      deprotonation of the substrate. Molecular orbital calculations demonstrate that
      such a (partial) deprotonation increases (a) the overall reactivity of 3
      fluorophenol for an electrophilic attack and (b) the reactivity of C2 relative to
      the C6 position. The hypothesis may explain the decrease in the C6/C2
      hydroxylation ratio. Furthermore the increased amount of ortho-hydroxylated
      products formed with increasing pH can also be explained by this hypothesis.

PMID- 8269924
TI  - Expression in yeast of three allelic cDNAs coding for human liver P-450 3A4.
      Different stabilities, binding properties and catalytic activities of the yeast
      produced enzymes.
AB  - Three natural allelic cDNAs coding for P-450 3A4, the major form in human liver,
      namely NF25, NF10 and hPCN1, have been expressed in Saccharomyces cerevisiae.
      NF25 and hPCN1 were functionally expressed in yeast microsomes, yielding proteins
      with an absorption maximum at 448 nm in the CO-reduced difference spectrum. Some
      catalytic activities and substrate binding properties of P-450 NF25 and P-450
      hPCN1 in yeast microsomes have been compared; no striking difference was found,
      showing that the two point substitutions between their amino-acid sequences
      (Trp392 and Thr431 in P-450 NF25 are replaced by Val392 and Ile431 in P-450
      hPCN1) have no significant effect on the functional properties of these two
      variants. By contrast, P-450 NF10, which differs from P-450 NF25 by a one-amino
      acid deletion (Ile224 replacing Thr224-Val225), was produced as a denatured form,
      as revealed by an absorption maximum at 420 nm, and was not catalytically active.
      This suggests that the deletion prevents the correct folding of the protein. The
      results of this study show that P-450 NF25 and P-450 hPCN1 are two roughly
      equivalent, functionally active variants of P-450 3A4, but that P-450 NF10 is a
      defective, unstable gene product that could arise from an alternative mRNA
      splicing. This could contribute to the large variations reported for nifedipine
      oxidation, a typical P-450 3A4 activity, in human liver.

PMID- 8269925
TI  - Erythritolteichoic acid in the cell wall of Glycomyces tenuis VKM Ac-1250.
AB  - The cell wall of Glycomyces tenuis VKM Ac-1250 contains the teichoic acid unusual
      for bacteria. The teichoic acid is a 1,4-poly(erythritol phosphate) chain
      composed of about 23 erythritol phosphate units, four or five of which have a 2
      acetamido-2-deoxy-alpha-D- glucopyranosyl substituent at C2(3) of erythritol. The
      polymer contains O-acetyl groups. Its structure was identified by chemical
      analysis as well as 1H-NMR and 13C-NMR spectroscopy. No teichoic acid containing
      a poly(erythritol phosphate) chain has yet been found in Gram-positive bacteria.

PMID- 8269926
TI  - Purification of ATP synthase from beef heart mitochondria (F0F1) and co
      reconstitution with monomeric bacteriorhodopsin into liposomes capable of light
      driven ATP synthesis.
AB  - ATP synthase was isolated from beef heart mitochondria by extraction with N,N-bis
      (3-D-gluconamidopropyl)deoxycholamide or by traditional cholate extraction. The
      enzyme was purified subsequently by ion-exchange and gel-permeation
      chromatographies in the presence of glycerol and the protease inhibitor
      diisopropylfluorophosphate. The ATP synthase consisted of 12-14 subunits and
      contained three tightly bound nucleotides. The co-reconstitution of crude or
      purified ATP synthase with monomeric bacteriorhodopsin by the method of detergent
      incubation of liposomes yielded proteoliposomes capable of light-driven ATP
      synthesis, as detected with a luciferase system for at least 30 min. The reaction
      was suppressed by the inhibitors oligomycin (> 90%) and dicyclohexylcarbodiimide
      (85%) and by the uncoupler carbonylcyanide-p-trifluormethoxyphenylhydrazone (>
      95%). The purified ATP synthase was apparently free of cytochrome impurities and
      of adenylate kinase activity, i.e. the enzyme exhibited light-driven ATP
      synthesis without the dark reaction. For the first time, this is demonstrated
      with purified ATP synthase from beef heart mitochondria.

PMID- 8269927
TI  - Hydrophobic mismatch and long-range protein/lipid interactions in
      bacteriorhodopsin/phosphatidylcholine vesicles.
AB  - Mismatch between the hydrophobic thicknesses of transmembrane proteins and the
      supporting lipid bilayer and its consequences on the lateral organization of
      lipids have been investigated with bacteriorhodopsin and phosphatidylcholine
      species with a variety of acyl-chain lengths. The purple membrane, from the
      bacterium Halobacterium halobium, was used and reconstituted with dilauroyl
      (Lau2GroPCho), dimyristoyl- (Myr2GroPCho), dipalmitoyl- (Pam2GroPCho) and
      distearoyl- (Ste2GroPCho) glycerophosphocholine. The phase behaviour of the
      lipids was investigated at different temperatures and different protein/lipid
      molar ratios, by analyzing the fluorescence excitation spectra of the 1-acyl-2-[8
      (2-anthroyl)-octanoyl]-sn-glycero-3-phosphocholine probe, and by measuring the
      fluorescence depolarization of the 1,6-diphenyl-1,3,5-hexatriene probe. Data
      obtained with 1-acyl-2-[8-(2-anthroyl)-octanoyl]-sn-glycero-3-phosphocholine
      shows that bacteriorhodopsin produced positive or negative shifts in the phase
      transition temperature of the host lipids depending on the strength and sign of
      the mismatch between the lipid and protein hydrophobic thicknesses and also on
      the protein concentration and aggregation state in the lipid bilayer. In the
      region of high protein concentration (bacteriorhodopsin/phosphatidylcholine molar
      ratios approximately 1:50) and despite the presence of the endogenous lipids,
      bacteriorhodopsin (hydrophobic length dP approximately 3.0-3.1 nm) brought about
      a large upward shift in the phase-transition temperature of Lau2GroPCho (delta T
      approximately 40 K, mean hydrophobic thickness d approximately 2.4 nm), and to a
      lesser extent of Myr2GroPCho (delta T approximately 23 K, d approximately 2.8
      nm), accounting for a strong rigidifying effect of the protein on these short
      chain lipids. Bacteriorhodopsin had no influence on the phase properties of
      Pam2GroPCho (delta T approximately 0 K, d approximately 3.2 nm), a lipid whose
      mean hydrophobic thickness is similar to that of the protein. In contrast, the
      transition temperature of Ste2GroPCho was decreased (delta T approximately -13 K,
      d approximately 3.7 nm), indicating a fluidifying effect of the protein on this
      long-chain lipid. Similar effects on the lipid acyl-chain order were observed in
      the region of high-protein dilution (bacteriorhodopsin/phosphatidylcholine molar
      ratios < 1:500). In this region and for Lau2GroPCho, both the spectroscopic data
      and circular-dichroism spectra indicated that the protein was in the monomeric
      form. Phase diagrams, in temperature versus bacteriorhodopsin concentration, were
      constructed for Lau2GroPCho and Ste2GroPCho. On account of microscopic
      theoretical models and of the relative values of dP and d, these diagrams
      indicate a preference of the protein for those lipid molecules which are in the
      gel-ordered state in Lau2GroPCho but in the liquid disordered state in
      Ste2GroPCho.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8269928
TI  - Regulation of the PDA1 gene encoding the E1 alpha subunit of the pyruvate
      dehydrogenase complex from Saccharomyces cerevisiae.
AB  - Expression of the PDA1 gene encoding the E1 alpha subunit of the pyruvate
      dehydrogenase complex (PDH complex) and activity of the complex were investigated
      in cells grown under several conditions. Comparable amounts of PDA1 mRNA and E1
      alpha subunit were detected in cells from batch and chemostat cultures grown on
      various carbon sources, showing constitutive expression of PDA1 at the
      transcriptional and translational levels. Induction of the regulatory GCN4
      mechanism upon histidine starvation, using the anti-metabolite 3-amino-1,2,4
      triazole, increased the levels of PDA1 mRNA by approximately 40%. However, a
      corresponding increase of E1 alpha concentration or activity of the PDH complex
      could not be detected. Hence, expression of the PDA1 gene is only regulated to a
      small extent, if at all, by the GCN4 mechanism. Contrary to the constant levels
      of PDA1 mRNA and E1 alpha subunit in both batch and chemostat cultures, the
      specific activity of the PDH complex varied with the culture conditions. The
      activity of the PDH complex in chemostat cultures was approximately two-threefold
      higher than in batch cultures grown on the same carbon sources. Overproduction of
      the E1 alpha subunit in batch cultures resulted in a two-threefold increase in
      the activity of the PDH complex. Taken together, these results indicate that the
      activity of the PDH complex is mainly regulated by post-translational
      modification of the E1 alpha subunit. Expression of PDA1 and activity of the PDH
      complex were also detected in cultures grown under conditions where no
      physiological significance of the PDH complex was expected, i.e. during anaerobic
      growth on glucose or aerobic growth on ethanol. Apparently, the switch from
      oxidative growth to fermentation occurs without much effect on the PDH complex.
      These observations suggest that the PDH complex has an alternative function
      besides sugar catabolism.

PMID- 8269929
TI  - Induction of translational thermotolerance in liver of thermally stressed rats.
AB  - Heat-shock gene expression in cultures of single cell types has been well
      characterized but little is known about the heat-shock response of intact organs
      in vivo. In this study, the kinetics of hepatic heat-shock gene expression and
      the induction of thermotolerance were characterized in rats. Animals were
      subjected to a defined, reversible stress by increasing the core body temperature
      to 41 degrees C or 42 degrees C for 30 min. New synthesis of the inducible form
      of the heat shock-70 family of proteins (hsp-72) peaked simultaneously with the
      maximal level of hsp-72 transcripts at both temperatures. These data are
      consistent with previous observations in cultures of hepatoblastoma cells after
      thermal stress [De Maio, A., Beck, S. C. & Buchman, T. G. (1993) Circ. Shock 40,
      177-186]. The incorporation of radioactive amino acids into polypeptides by the
      liver was blocked during the first hour of recovery after heat shock at 42
      degrees C. This inhibition of protein synthesis by thermal stress could be
      prevented by prestressing rats at 42 degrees C for 30 min and allowing the rats
      to recover for 24 h at normal body temperature (37 degrees C). This phenomenon,
      previously defined as 'translational thermotolerance', correlates with the
      hepatic content of hsp-72; maximal protection occurs 24 h after a 42 degrees C
      thermal stress when hsp-72 (protein) is also maximum and decreases with the
      clearance of hsp-72 from the liver. These data suggest that the presence of hsp
      72 within the liver may modulate the organ response to subsequent stresses and
      may be important to organ and animal survival after repeated insults.

PMID- 8269930
TI  - Interferon-gamma up-regulates a unique set of proteins in human keratinocytes.
      Molecular cloning and expression of the cDNA encoding the RGD-sequence-containing
      protein IGUP I-5111.
AB  - Treatment of proliferating and quiescent primary human keratinocytes with
      interferon-gamma (IFN-gamma) (100 U/ml, 23.5 h) followed by two-dimensional gel
      analysis revealed three proteins, IGUP I-3421 (M(r) = 48,200, pI = 6.06); IGUP I
      3524 (M(r) = 56,900, pI = 5.92), a protein homologous to peptide-chain-release
      factor and tryptophanyl-tRNA synthetase; and IGUP I-5111 (M(r) = 30,400, pI =
      5.76) recorded in the keratinocyte protein database (Celis et al., 1991, 1992)
      that are highly and specifically up-regulated by IFN-gamma among several agents
      tested including 14 other cytokines, second messengers [dibutyryl cAMP (Bt2cAMP),
      dibutyryl cGMP (Bt2cGMP)] and compounds known to affect keratinocytes [4 beta
      phorbol 12-myristate 13-acetate (PMA), retinoic acid, Ca2+, dexamethasone,
      lipopolysaccharides, foetal calf serum]. Protein IGUP I-5111 was selected for
      further studies as its level is affected by simian-virus-40 transformation and
      because peptide sequences were available in the microsequence database. The cDNA
      was cloned from a fibroblast cDNA library using degenerate
      oligodeoxyribonucleotides and expressed in AMA cells using the vaccinia virus
      expression system. Database searches indicated that the predicted protein, which
      migrated with the AMA variant of keratinocyte protein IEF SSP 5111, is novel
      although it exhibits weak similarity to cytoskeletal proteins. IGUP I-5111
      contains the RGD sequence found in many extracellular glycoprotein ligands of the
      integrin receptor family and it is found at least partially in the culture
      supernatant. Considering the presence of IFN-gamma in psoriatic plaques as well
      as its putative involvement in the pathophysiology of the disease it was of
      interest to determine whether the set of proteins was upregulated in these cells.
      Two-dimensional gel analysis of the protein phenotype of non-cultured,
      unfractionated psoriatic keratinocytes failed to reveal up-regulation of any of
      the three IFN-gamma-induced proteins suggesting that the effect of IFN-gamma in
      vivo may be modulated by the activity of other cytokine(s) or growth factor(s).
      Psoriatic keratinocytes were equally sensitive to IFN-gamma as their normal
      counterparts.

PMID- 8269931
TI  - Human progelatinase A can be activated by autolysis at a rate that is
      concentration-dependent and enhanced by heparin bound to the C-terminal domain.
AB  - Activation of the latent precursor of human gelatinase A (progelatinase A) was
      investigated using recombinant proenzyme purified from culture medium conditioned
      by transfected mouse myeloma cells. A 4.0 microM progelatinase A solution was
      activated to a maximum of 48% of the activity produced by 4-aminophenylmercuric
      acetate (APMA) simply by its incubation at 37 degrees C for 12 h, though at lower
      starting concentrations the rate and extent of activation were reduced.
      Activation was shown to be the result of a single autolytic cleavage at the Asn80
      Tyr81 peptide bond that removes the propeptide and converts the M(r) = 72,000
      proenzyme into the M(r) = 66,000 active species also produced by APMA activation.
      It is proposed that this cleavage is a bimolecular event catalysed by previously
      activated gelatinase A. The addition of heparin increased by approximately
      eightfold the initial rate of progelatinase A autolytic activation but did not
      affect the activation of a deletion mutant that lacked the C-terminal domain [des
      (418-631)progelatinase A]. The inference that this increase resulted from an
      interaction between heparin and the C-terminal domain was supported by the
      finding that, unlike des-(418-631)gelatinase A, both full-length gelatinase A and
      the isolated C-terminal domain were able to bind to heparin-Sepharose CL-6B and
      that, at NaCl concentrations sufficient to abolish this binding, heparin had no
      effect. We conclude that heparin is able to enhance autolytic activation by
      acting as a template that approximates active-->latent gelatinase A and suggest
      that a similar mechanism may account for the cell-surface activation of this
      enzyme.

PMID- 8269932
TI  - Kinetic studies of pea carbonic anhydrase.
AB  - Chloroplast carbonic anhydrase from Pisum sativum has been isolated. The kinetic
      properties of the enzyme have been studied and comparisons to the well
      characterised human carbonic anhydrase II made. Pea carbonic anhydrase was found
      to be dependent on a reducing agent in order to retain the catalytic activity.
      Oxidised, inactive, enzyme could be activated by the addition of a SH-agent.
      However, such activation gave only 60% of the activity of an enzyme kept in a
      reduced state all the time. The kinetics of CO2 hydration show an increase in
      kcat as well as in kcat/Km with pH, but the pH profile does not follow a simple
      titration curve. The pH dependence is more complicated and it seems as if there
      are several titratable groups affecting the activity. At pH 9 we obtain a
      turnover number of 4 x 10(5) s-1 and a kcat/Km value of 1.8 x 10(8) M-1 s-1 with
      reference to the subunit. We also find that the enzyme needs high concentrations
      of buffer to work at a maximal rate. Apparent Km values with respect to the total
      buffer concentration are found between 52-185 mM at neutral and high pH. At low
      pH the situation is complex with deviations from Michaelis-Menten kinetics.
      Chloroplast carbonic anhydrase from higher plants have been reported to have
      primary structures that are completely different from the enzyme from animals. In
      addition, we find the circular dichroic spectrum of pea carbonic anhydrase to be
      well distinguished from that of human carbonic anhydrase II. Despite those
      structural differences the kinetic parameters indicate that pea carbonic
      anhydrase is equally efficient as human carbonic anhydrase II in catalysing the
      hydration of CO2. However, the mechanism for proton transfer from the active site
      to the surrounding medium seems to differ between the two enzymes.

PMID- 8269933
TI  - Photoaffinity labeling of the human red-blood-cell urea-transporter polypeptide
      components. Possible homology with the Kidd blood group antigen.
AB  - The tritiated urea analogue 1-(3-azido-4-chlorophenyl)-3methyl-2-thiourea
      ([3H]MeACPTU) was used as a probe to photolabel the human red-blood-cell membrane
      facilitated urea transporter. On irradiation, [3H]MeACPTU incorporated
      irreversibly into white ghost membranes. SDS/gel electrophoresis of membranes
      revealed radioactive incorporation in five major bands of 200, 110, 60, 40 and 14
      kDa. The labeling of the 40-kDa and 60-kDa bands was partly prevented by the
      presence of a high concentration of other urea analogues such as thiourea and 1
      (3,4-dichlorophenyl) 2-thiourea (DCPTU). The photolabeling pattern obtained with
      white ghosts of the Kidd blood-group type Jk(a-,b-) showed no labeling of the 40
      kDa polypeptide. Protecting experiments carried out with anti-Jka, anti-Jkb and
      anti-Jk3 sera prevented radioactive incorporation in the 60-kDa band and in the
      110-kDa band. Urea permeability of pink ghosts of blood type Jk(a+,b+) measured
      in the presence of Jk3 antibodies was 19% lower than the control values. However,
      urea permeability of frog urinary bladder epithelial cells was not affected by
      the presence of Jk-reactive antibodies. These results support the hypothesis that
      the Kidd antigen and the facilitated urea transporter are the same protein. Our
      estimation of the number of copies in each cell is close to that of the
      previously published value of 14000.

PMID- 8269934
TI  - Evolution of the monotremes. The sequences of the protamine P1 genes of platypus
      and echidna.
AB  - The protamine P1 genes from two monotremes, platypus (Ornithorhynchus anatinus)
      and echidna (Tachyglossus aculeatus) were isolated after polymerase-chain
      reaction amplification then cloned and sequenced. The two protamine P1 genes are
      of 290 bp and 311 bp for platypus and echidna, respectively, and are clearly
      orthologous to the published sequences of protamine P1 genes of eutherian mammals
      and birds. Both genes contain an intron, like the mammals and marsupials and
      unlike the bird P1 genes that are intronless. The deduced protein sequences from
      the coding areas of the platypus and echidna protamine P1 genes do not contain
      any cysteine residues. This absence of cysteine residues leaves the sperm nuclei
      susceptible to disruption in vitro by exposure to increasing ionic strength and
      is a characteristic of fish, birds and marsupials. In contrast, the P1 protamines
      of placental mammals invariably contain 6-9 cysteine residues that, as a result
      of the formation of intermolecular and intramolecular disulfide bridges,
      significantly increase the stability of the sperm nuclei that can only be
      disrupted following disulfide-bond cleavage. Phylogenetic analysis of the
      protamine P1 gene sequences indicates that the monotremes occupy a position half
      way between the eutherian mammals and birds. From the DNA sequences we estimate
      the time of divergence of the platypus and the echidna to be around 22 million
      years ago. This date agrees very well with the published estimates of divergence
      based on other criteria.

PMID- 8269935
TI  - Pressure-induced dissociation of ribosomes and elongation cycle intermediates.
      Stabilizing conditions and identification of the most sensitive functional state.
AB  - Pressure-induced dissociation of ribosomes has been considered a major reason for
      the inhibition of protein biosynthesis and, hence, bacterial growth at high
      hydrostatic pressure [Jaenicke, R. (1981) Annu. Rev. Biophys. Bioeng. 10, 1-67].
      We reexamined the issue, using a buffer system with polyamines that has been
      optimized to reproduce in-vivo-like performance of protein biosynthesis in vitro.
      By slightly modifying this buffer, we were able to find conditions that stabilize
      functional ribosomal complexes against the dissociating effect of pressure up to
      100 MPa and uncharged tight couples up to 60 MPa. Approaching the physiological
      conditions by reducing the Mg2+ concentration down to 4 mM, one finds a
      significant destabilization of the post-translocational complex, which represents
      the most pressure-sensitive intermediate of the elongation cycle and is possibly
      the limiting factor for the pressure-induced block of protein biosynthesis and
      bacterial growth.

PMID- 8269936
TI  - Ion-exchange reactions of proteins during DNA binding.
AB  - The equilibrium association constant observed for many DNA/protein interactions
      in vitro (K(obs)) is strongly dependent on the salt concentration of the reaction
      buffer ([MX]). This dependence is often used to estimate the number of ionic
      contacts between protein and DNA by assuming that displacement of cations from
      the DNA is the predominant form of the involvement of ions in the binding
      reaction. With this assumption, the graph of log K(obs) versus log [MX] is
      predicted to have a constant slope proportional to the number of ions displaced
      from the DNA upon protein binding [Record, M. T., Lohman, T. M. & deHaseth, P. L.
      (1976) J. Mol. Biol. 107, 145-158]. Experimental data often deviate from
      linearity, however, at lower salt concentrations. Such deviations can be due to
      differential cation binding, anion binding or changes in macromolecular
      hydration, or differential screening effects of the electrolyte on protein and/or
      DNA charges. Here the theoretical effects on K(obs) of a simple form of ion
      protein interaction are examined. A model for binding interactions is used that
      includes a mass balance of ions bound to both protein and DNA as the protein is
      transferred from the salt concentration of bulk solvent to the typically higher
      cation and lower anion concentrations characteristic of the volume adjacent to
      the DNA. We show that models in which the cation and anion stoichiometries of a
      protein change as it associates with DNA are consistent with the curvature of
      plots of log K(obs) versus log [MX]. Such mechanisms could reduce the sensitivity
      of gene-regulatory interactions to changes in environmental salt concentration.

PMID- 8269937
TI  - Coupling of recombinant 5-lipoxygenase and leukotriene A4 hydrolase activities
      and transcellular metabolism of leukotriene A4 in Sf9 insect cells.
AB  - High-level expression of human leukotriene (LT) A4 hydrolase has been established
      in Sf9 insect cells using the recombinant baculovirus system. LTA4 hydrolase
      activity in this system is at least 50-fold higher than previously achieved in a
      bacterial cell system. Recombinant viral human LTA4 hydrolase (rvHLTA4h) was used
      for coinfection studies with recombinant viral 5-lipoxygenase (rvH5LO). When Sf9
      cells expressing 5-lipoxygenase are incubated in the presence of A23187 and
      arachidonic acid, (5S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid 5
      H(P)ETE and LTA4 are synthesized in a ratio of 5:1 for 5-H(P)ETE/LT. Coexpression
      of 5-lipoxygenase and LTA4 hydrolase in these insect cells results in the
      synthesis of 5-H(P)ETE, LTA4 and in addition LTB4, and the ratio shifts to 2:1
      for 5-H(P)ETE/LT. The production of enzymically formed LTB4 after addition of
      arachidonic acid to the Sf9 cells coinfected with LTA4 hydrolase and 5
      lipoxygenase is the first demonstration of channeling of arachidonic acid to LTB4
      in an engineered intact cell system. This delineates a novel biological system to
      synthesize significant amounts of the potent chemotactic agent, LTB4. Studies in
      which Sf9 cells infected with rvH5LO were incubated with Sf9 cells infected with
      rvHLTA4h resulted in export of LTA4 from the rvH5LO cells and transcellular
      metabolism of LTA4 to LTB4 in the rvHLTA4h Sf9cells.

PMID- 8269938
TI  - Methylation state of the human HLA-DRA gene in T-lymphocytes and B-lymphocytes of
      transgenic mice. Lack of methylation at one 5'-GCGC site is not required for gene
      expression.
AB  - A consistent lack of DNA methylation at one or both of two GCGC (Hha I)
      restriction sites in the 5' region of the HLA-DRA gene has been previously
      documented by the use of methyl-sensitive restriction enzymes in human cells and
      tissues, irrespectively of their expression of DR alpha products. Evidence
      presently available, however, does not exclude that a lack of methylation in this
      region, although not sufficient, might be necessary for gene expression. In this
      report, we show that only one of the 5'-GCGC sites is protected, although less
      efficiently than in man, from CG-->mCG modifications in tissues and cells of
      transgenic mice carrying an expressed single copy of the HLA-DRA gene/diploid
      genome. We demonstrate that the two 5' GCGC sites of the HLA-DRA transgene are
      fully methylated in DR alpha- splenocytes (more than 80% T-lymphocytes), while
      one of them (the most 5' site) is not methylated in a fraction of DR alpha+
      splenocytes (more than 95% B-lymphocytes). These results provide evidence that
      absence of DNA methylation in the 5' region is not necessary for, but might be
      associated with and possibly secondary to the expression of the DRA gene.

PMID- 8269940
TI  - The actin monomers in the ternary gelsolin: 2 actin complex are in an
      antiparallel orientation.
AB  - Gelsolin forms ternary complexes with two actin monomers in the presence of Ca2+,
      which nucleate actin polymerization and cap the barbed ends of filaments. It has
      therefore been assumed that the two actins are oriented in a similar manner to
      the terminal subunits in the genetic helix of F-actin. We have tested this using
      chemical cross-linking with N,N'-1,4-phenylenedimaleimide. For all conditions
      tested, we identified as the only cross-linked dimeric species an actin dimer
      indistinguishable from the lower actin dimer of 86 kDa. This lower dimer was
      previously identified in the initial phase of actin polymerization and also when
      actin paracrystals are chemically cross-linked [Millonig, R., Salvo, H. & Aebi,
      U. (1988) J. Cell Biol. 106, 785-796]. It probably defines a contact between
      adjacent monomers oriented in an antiparallel orientation. In contrast, when F
      actin is cross-linked by the same reagent, an upper dimer of apparent molecular
      mass 115 kDa is formed, which corresponds to adjacent monomers in the genetic
      helix. The formation of this upper dimer was specifically inhibited by addition
      of gelsolin to F-actin. Evidence is presented for a Cys374-Cys374 cross-link in
      the lower dimer. Isolated lower dimer binds to gelsolin in a 1:1 stoichiometry,
      but it inhibits nucleation of polymerization by gelsolin. Other gelsolin
      constructs that bind two actin subunits (e.g. the N-terminal half of the
      molecule, which has severing and capping but no nucleating activity) also form
      only lower dimer when cross-linked with N,N'-1,4-phenylenedimaleimide. Only
      segment 2-6 (gelsolin fragment devoid of the N-terminal segment 1) induces an
      upper dimer orientation of the two actins under nucleating conditions. Our
      evidence suggests that the two actins associated with gelsolin are not fixed in
      the orientation of adjacent subunits in F-actin; instead they have a flexible
      orientation with respect to each other, which permits cross-linking into a stable
      antiparallel form that does not correspond to the presumed nucleating
      conformation.

PMID- 8269939
TI  - Big endothelin-1 structure important for specific processing by endothelin
      converting enzyme of bovine endothelial cells.
AB  - Phosphoramidon-sensitive endothelin-converting enzyme of bovine endothelial cells
      showed substrate selectivity for big endothelin-1 (ET-1) when compared to big ET
      1(1-38), big ET-2(1-37), big ET-2(1-38) and big ET-3(1-41). To investigate the
      big ET-1 structure important for specific conversion by the endothelin-converting
      enzyme, we synthesized a series of truncated analogues of big ET-1, measured the
      hydrolysis of their Trp21-Val22 bonds, and found that a 16-residue peptide, big
      ET-1(19-34), is the minimal peptide sequence. This suggests that an unusually
      long carboxy-terminal sequence is required for big ET-1 conversion. Alanine
      substitution for individual amino acids in the carboxy-terminal region of big ET
      1(19-34) demonstrated that His27, Val29, Pro30, Tyr31, Gly32, Leu33 and Gly34 are
      more important than Asn23, Thr24, Pro25, Glu26 and Val28 for eliciting efficient
      hydrolysis of the Trp21-Val22 bond, even though the former residues are located
      at more distant positions from the cleavage sites than are the latter. These
      results, together with the fact that big ET-2 and big ET-3 show heterogeneity in
      the big ET-1 residues His27, Val28, Val29 and Gly34, suggest that the His27-Val
      Val-Pro-Tyr-Gly-Leu-Gly34 sequence in the carboxy-terminal region of big ET-1
      plays the most important role in selective conversion by endothelin converting
      enzyme.

PMID- 8269941
TI  - Ser2 is the autophosphorylation site in the beta subunit from bicistronically
      expressed human casein kinase-2 and from native rat liver casein kinase-2 beta.
AB  - Human casein kinase-2 (CK-2) subunits alpha and beta were bicistronically
      expressed in bacteria. The recombinant holoenzyme shared all investigated
      properties with the native CK-2 from mammalian sources (rat liver, Krebs II mouse
      ascites tumour cells). Contrary to recombinant human CK-2 produced by self
      assembly in vitro, the bicistronically expressed beta subunit was
      autophosphorylated during formation of the holoenzyme in bacteria. Electrospray
      ionisation mass spectrometry (ESI) revealed Ser2 (second amino acid, first
      serine) as the only phosphate acceptor site. Kinetic data obtained with either
      the phosphorylated or the unphosphorylated form of CK-2 did not differ
      significantly, suggesting that the autophosphorylation had no influence on the
      kinetic parameters Km and Vmax. In parallel, native rat liver CK-2 beta subunit
      was shown to incorporate 0.1 mol phosphate/mol holoenzyme, which suggests that
      the enzyme is already heavily phosphorylated. ESI analysis also revealed Ser2 as
      the only phosphorylated residue at the amino terminus. In the case of both
      recombinant human CK-2 and native rat liver CK-2, treatment with alkaline
      phosphatase readily reversed the phosphorylated form of the beta subunit to the
      faster migrating dephosphorylated polypeptide.

PMID- 8269942
TI  - Synergistic binding of hydrophobic probes and zinc ligands to thermolysin.
AB  - The strong synergism previously observed in the binding of inhibitors to two Zn
      proteases, has also been found for thermolysin. As in earlier cases, the effects
      are produced by a small Zn-ligand (e.g. a hydroxamate) in the presence of another
      compound which contains the key structural features of specific substrates (a
      specificity probe). For thermolysin, the most effective specificity probes are
      hydrophobic derivatives of amines and amino acids (e.g. carbobenzyloxy-L
      alaninol). Even the simple combination of benzyl alcohol and formohydroxamate
      displays considerable synergism. The above effects are temperature dependent and
      correlate well with a thermally induced conformational isomerization reported
      recently for this enzyme. Our results seem to be related to previous observations
      of substrate synergism in the reverse reaction and to superactivation by chemical
      modification of this enzyme. All these effects are consistent with a change in
      the environment of the catalytically important zinc atom upon binding of the
      hydrophobic side chain of the substrate. With the inclusion of thermolysin,
      binding synergism is now known to occur in an endopeptidase as well as in
      exopeptidases of diverse specificity. The general occurrence of this phenomenon
      in zinc proteases and its possible significance are discussed in an accompanying
      study.

PMID- 8269943
TI  - General occurrence of binding synergism in zinc proteases and its possible
      significance.
AB  - The observation of binding synergism has been successfully extended to include
      carboxypeptidases A and B. The behaviour of these two enzymes follows the same
      pattern previously found for three other Zn-proteases. Thus in all cases
      examined, the affinity of a suitable Zn-ligand is increased in the presence of a
      compound (specificity probe) which contains the key structural features of
      specific substrates. A bifunctional ligand such as phosphonoacetate is
      particularly useful for generating synergism in both carboxypeptidases.
      Presumably the carboxylate moiety binds to the C-terminal recognition site while
      the other functional group interacts with the metal ion. Several basic compounds
      (e.g. methyl guanidine) act as effective specificity probes for carboxypeptidase
      B while phenol and other hydrophobic substances serve this purpose in
      carboxypeptidase A. The above phenomenon appears to be a mechanism designed to
      enhance catalytic efficiency through a substrate-induced conformational change.
      We postulate that there is a requirement for at least one ionizable group at the
      active site. The proposed mechanism keeps this group in the correct ionization
      state in the presence of water and increases its reactivity after exclusion of
      water by substrate binding. We suggest the term xerophilic shift for this
      process. Since proton transfer is a common process in enzyme reactions, the
      xerophilic-shift mechanism may play a similar role in many instances. It should
      therefore be possible to detect binding synergism in a wide variety of enzymes.

PMID- 8269944
TI  - Purification and properties of N-acetylglucosaminidase from eggs of the ascidian,
      Halocynthia roretzi.
AB  - In several ascidians, beta-D-N-acetylglucosaminidase (GlcNAcase) released from
      eggs following fertilization is proposed to play a key role in polyspermy block
      through its binding to the sperm receptor on the vitelline coat [C. C. Lambert
      (1989) Development 105, 415-420]. In the ascidian Halocynthia roretzi, GlcNAc
      specific lectins inhibited the fertilization most strongly among various lectins.
      Furthermore, GlcNAcase activity was released from the eggs in response to the egg
      activation. The GlcNAcase was purified from the eggs to apparent homogeneity by
      chromatographies on DEAE-Toyopearl, SP-Toyopearl, Toyopearl HW-65, and Mono S.
      The purified enzyme gave a single band on isoelectric focusing with an
      isoelectric point of 7.0. It gave two bands on SDS/PAGE: the molecular masses of
      the bands were estimated to be 65 kDa/66 kDa, and 84 kDa/85 kDa under
      reducing/non-reducing conditions, respectively. The two bands were found to
      converge to a single band of 56 kDa after deglycosylation, which suggests
      microheterogeneity in the sugar moiety. The enzyme showed an oligomeric structure
      with an apparent molecular mass of 520 kDa, estimated by gel filtration. The
      optimum pH of the activity was around 4.5. The enzyme hydrolyzed both 4
      methylumbelliferyl-GlcNAc and 4-methylumbelliferyl-GalNAc, suggesting that it
      should be characterized as a beta-D-N-acetylhexosaminidase, with Km values of 1.2
      mM and 0.52 mM, respectively. The purified enzyme was found to be capable of
      binding to the vitelline coat in a GlcNAc-specific manner. Immunoblot analysis
      using antibody raised against the purified GlcNAcase revealed that the enzyme
      itself is released from the eggs upon fertilization. Thus, the GlcNAcase purified
      in this study is released from eggs following fertilization and bound to the
      vitelline coat in order to function in the polyspermy blocking mechanism.

PMID- 8269945
TI  - The structure of the carbohydrate backbone of the core-lipid-A region of the
      lipopolysaccharide from Vibrio cholerae strain H11 (non-O1).
AB  - Lipopolysaccharide from Vibrio cholerae strain H11 (non-O1) was de-O-acylated,
      dephosphorylated, reduced, de-N-acylated, N-acetylated, and the products were
      separated by high-performance anion-exchange chromatography (HPAE). A
      decasaccharide, 1, was isolated as the major product, representing the core
      oligosaccharide attached to the reduced GlcN-disaccharide lipid A backbone. Its
      structure was established by compositional and methylation analyses, and
      extensive NMR investigations including 1H,1H correlation spectroscopy (COSY),
      total correlation spectroscopy (TOCSY), and nuclear Overhauser enhancement
      spectroscopy (NOESY), as well as heteronuclear 13C,1H COSY. In another reaction
      sequence the lipopolysaccharide was hydrolysed with dilute acetic acid and
      reduced with NaBH4. The resulting core fractions were separated by HPAE giving
      seven individual octasaccharides differing at the reducing 3-deoxy-D-manno
      octulosonic acid (Kdo) residue. A major product, 2, was isolated and investigated
      by the same methods as described for the decasaccharide 1. The following
      structures are proposed for compounds 1 and 2: alpha-D-GlcNAcp-(1-7)-[beta-D-Galp
      (1-3)-]-alpha-Hepp-(1-2)- alpha-Hepp- (1-3)-[beta-D-Glcp-(1-4)-]- [alpha-D-Glcp
      (1-6)-]-alpha-Hepp-(1-5)-R, where R is alpha-Kdop-(2-6)-beta-D-GlcNAcp-(1-6)-D
      GlcNAcol in 1 and 4,8-anhydro-Kdool in 2, and Hep is L-glycero-D-manno-heptose.
      In lipopolysaccharide, the terminal residue of alpha-D-glucosamine possessed a
      free amino group, as proved by deamination with nitrous acid and the 1H-NMR
      spectrum of de-O-acylated lipopolysaccharide. The conformational preferences of
      the terminal core heptasaccharide was assessed by Monte Carlo simulations
      combined with restrained calculations of side chains based on experimentally
      determined proton-coupling constants. These calculations, confirmed by NOE data,
      displayed several long-range interactions, which resulted in a well-defined three
      dimensional structure of the core oligosaccharide.

PMID- 8269946
TI  - Influence of the supramolecular structure of free lipid A on its biological
      activity.
AB  - The three-dimensional supramolecular structures and the states of order of the
      acyl chains of lipid A from different Gram-negative species were investigated at
      40 degrees C, high water content (80-90%), and different [lipid A]/[Mg2+] molar
      ratios using synchrotron radiation X-ray diffraction and Fourier-transform
      infrared spectroscopy. Measurements were made on free lipid A from Salmonella
      minnesota R595, mono- and bi-phosphoryl, as well as those from the non
      enterobacterial strains Rhodobacter capsulatus 37b4, Rhodopseudomonas viridis F,
      and Rhodocyclus gelatinosus 29/1. Parallel to differences in their chemical
      primary structure, the structural polymorphisms and states of order at 37 degrees
      C of the non-enterobacterial lipid A were found to be different from those of
      enterobacterial lipid A. A clear correlation between the supramolecular structure
      and previously determined biological activities was found. Lipid A with a strong
      preference for lamellar structures (Rb. capsulatus and Rp. viridis) are
      endotoxically inactive and lack cytokine-inducing capacity; the compounds
      assuming a mixed lamellar/nonlamellar structure (monophosphoryl lipid A from S.
      minnesota) are of lower toxicity in vivo, but may induce cytokines in vitro;
      those lipid A with a strong tendency to form non-lamellar inverted structures
      (lipid A from S. minnesota and Rc. gelatinosus) exhibit full endotoxicity in
      vitro and in vivo. In contrast, anti-complementary activity is most pronounced
      for compounds with lamellar and least expressed for those with inverted
      structures. The states of order at 37 degrees C vary non-systematically,
      exhibiting the highest values for lipid A of S. minnesota and the lowest for that
      of Rc. gelatinosus. We propose to extend the term 'endotoxic conformation', which
      is used to describe the conformation of a single lipid A molecule required for
      optimal triggering of biological effects, to 'endotoxic supramolecular
      conformation' which denotes the particular organization of lipid A aggregates in
      physiological fluids causing biological activity.

PMID- 8269947
TI  - Analysis of two mutated vacuolar proteins reveals a degradation pathway in the
      endoplasmic reticulum or a related compartment of yeast.
AB  - The fate of a mutant form of each of the two yeast vacuolar enzymes proteinase
      yscA (PrA) and carboxypeptidase yscY (CPY) has been investigated. Both mutant
      proteins are rapidly degraded after entering the secretory pathway. Mutant PrA is
      deleted in 37 amino acids spanning the processing site region of the PrA pro
      peptide. The mutant enzyme shows no activity towards maturation of itself or
      other vacuolar hydrolases, a function of wild-type PrA. Mutant CPY carries an Arg
      instead of a Gly residue in a highly conserved region, two positions distant from
      the active-site Ser. In contrast to wild-type CPY, the mutant form was quickly
      degraded by trypsin in vitro, indicating an altered structure. Using antisera
      specific for alpha-1-->6 and alpha-1-->3 outer-chain mannose linkages, no Golgi
      specific carbohydrate modification could be detected on either mutant protein.
      Subcellular fractionation studies located both mutant enzymes in the endoplasmic
      reticulum. Degradation kinetics of both proteins show the same characteristics,
      indicating similar degradation pathways. The degradation process was shown to be
      independent of a functional sec18 gene product and takes place before Golgi
      specific carbohydrate modifications occur. The proteasome, the major proteolytic
      activity of the cytoplasm, is not involved in this degradation event. All
      degradation characteristics of the two mutant proteins are consistent with a
      degradation process within the endoplasmic reticulum ('ER degradation').

PMID- 8269948
TI  - A drug-resistant variant of topoisomerase II alpha in human HL-60 cells exhibits
      alterations in catalytic pH optimum, DNA binding and sub-nuclear distribution.
AB  - Anion-exchange chromatography of partially purified human HL-60 topoisomerase II
      resolves the known alpha (170 kDa) and beta (180 kDa) isoenzymes at 150 mM NaCl
      and 230 mM NaCl, respectively. An additional topoisomerase II fraction was eluted
      by > 300 mM NaCl. It could be identified by Western blotting as a late-eluting
      variant of topoisomerase II alpha, which is functionally altered as compared to
      the early-eluting form, having the following properties: a shift in the catalytic
      optimum to pH 9; increased stability in DNA complex formation; approximately 100
      fold resistance to orthovanadate; approximately 1000-fold resistance to the
      cytostatic substances N-[4-(9-acridinylamino)-3-methoxyphenyl]
      methanesulphonamide (amsacrine) and the podophyllotoxin etoposide (VP 16). 80% of
      the late-eluting topoisomerase II alpha could be captured by SDS on calf thymus
      DNA without further enhancement by drugs. In contrast, the early-eluting
      topoisomerase II alpha exhibits 10% complex formation with SDS alone, and an
      increase to 90% complex formation in the presence of drugs. A HL-60 subline (HL
      60/R), approximately 1000-fold resistant to etoposide and amsacrine, has
      equivalent proportions of topoisomerase II alpha and topoisomerase II beta and
      similar levels of both isoenzymes, as compared to the drug-sensitive HL-60/WT
      cells. However, determination of the cellular levels of the early-eluting and
      late-eluting forms of topoisomerase II alpha revealed that the HL-60/R cell line
      contains approximately 80% of the late-eluting topoisomerase II alpha, whereas
      the sensitive HL-60/WT cell line contains only 15-20% of this form. The nuclear
      distribution of the two forms also differs. Sensitive HL-60/WT cells show a
      diffuse nuclear distribution but in resistant cells the distribution is localized
      in the nucleoli. Apparently two functionally distinct subforms of topoisomerase
      II alpha coexist in drug-sensitive and drug-resistant HL-60 cells and changes in
      their relative levels affect the cellular sensitivity to topoisomerase-II
      targeting drugs.

PMID- 8269949
TI  - Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human
      livers, and its transcriptional control.
AB  - CYP3 A4 is the adult-specific form of cytochrome P450 in human livers [Komori,
      M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. &
      Kamataki, T. (1990) Biochemistry 29, 4430-4433]. The sequences of three genomic
      clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5'
      flanking region from the major transcription site to nucleotide position -1105,
      and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome
      P450 in humans. The results showed that the identity of 5'-flanking sequences
      between CYP3A4 and CYP3A7 genes was 91%, and that each 5'-flanking region had
      characteristic sequences termed as NFSE (P450NF-specific element) and HFLaSE
      (P450HFLa specific element), respectively. A basic transcription element (BTE)
      also lay in the 5'-flanking region of the CYP3A4 gene as seen in many CYP genes
      [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell.
      Biol. 10, 1470-1475]. The BTE binding factor (BTEB) was present in both adult and
      fetal human livers. To examine the transcriptional activity of the CYP3A4 gene,
      DNA fragments in the 5'-flanking region of the gene were inserted in front of the
      simian virus 40 promoter and the chloramphenicol acetyltransferase structural
      gene, and the constructs were transfected in HepG2 cells. The analysis of the
      chloramphenicol acetyltransferase activity indicated that (a) specific element(s)
      which could bind with a factor(s) in livers was present in the 5'-flanking region
      of the CYP3A4 gene to show the transcriptional activity.

PMID- 8269950
TI  - Alanine scanning mutagenesis of human erythropoietin identifies four amino acids
      which are critical for biological activity.
AB  - Erythropoietin regulates the growth and proliferation of red blood cell
      progenitors. We demonstrated previously the important structural and functional
      roles of the amino acid region 99-110 in the biological activity of the hormone.
      [Chern, Y., Chung, T. & Sytkowski, A. J. (1991) Eur. J. Biochem. 202, 225-229].
      We have now performed alanine scanning mutagenesis to identify which specific
      residues in this region are essential for function. Four substitutions reduced
      the biological activity of erythropoietin. Alanine substitution of Ser104, Leu105
      and Leu108 reduced activity to 16, 44, and 37% that of the wild-type protein,
      respectively. Most significantly, substitution of Arg103 with Ala reduced
      activity to undetectable levels, indicating a > 230-fold reduction in specific
      activity. Immunochemical analyses using anti-peptide monoclonal antibodies
      demonstrated that this substitution does not cause major changes in the
      conformation of the protein or large, localized distortions within the amino acid
      region 99-129 of the molecule. Heat-denaturation kinetics for the arginine mutant
      and wild-type erythropoietin are virtually identical, further indicating the
      structural similarity between these two molecules. Based upon these findings, we
      propose that Arg103 plays an essential role in the biological activity of
      erythropoietin, presumably by interacting directly with the erythropoietin
      receptor.

PMID- 8269951
TI  - Preferential sites of proteolytic cleavage of bovine, human and rat
      thyroglobulin. The use of limited proteolysis to detect solvent-exposed regions
      of the primary structure.
AB  - The sites and the sequence of the proteolytic cleavages of bovine, human and rat
      thyroglobulin, during the limited proteolysis with thermolysin and trypsin, were
      determined by sequencing the NH2 termini of the peptides produced and comparing
      them to the cDNA-derived sequences of bovine, human and rat thyroglobulin. Major
      cleavage sites of bovine thyroglobulin included residues 240, 502, 993, 1218,
      1784 with thermolysin, and 240, 520, 1142, 1783, 2515 with trypsin. Cleavage
      sites of human thyroglobulin included residues 503, 982, 990, 1405, 1831 with
      thermolysin, and 522, 1627, 2513 with trypsin. Those of rat thyroglobulin
      included residues 501, 1776, 1784 with thermolysin, and 522, 1771, 1825, 2515
      with trypsin (numbered as in bovine thyroglobulin). Thus, thyroglobulin from
      various species presents well localized and conserved regions particularly
      sensitive to proteolysis. The most sensitive region extended for 30 residues
      after residue 500. Another major cluster of cleavages was centered around residue
      1800; this region was only partially sensitive in human thyroglobulin. A
      conserved tryptic site lay at the COOH terminus of the molecule. Most cleavage
      sites occurred within the inserted sequences that disrupt the Cys-rich, tandem
      repeats of thyroglobulin and either contain or are located near exon-intron
      junctions. Several cleavage sites lay in proximity of early iodinated or
      hormonogenic tyrosyl residues or of putative N-linked glycosylation sites. While
      a predominantly beta-type secondary structure and a rigid three-dimensional
      structure were predicted for the Cys-rich repeats, stretches of predicted alpha
      helices, beta-strands and irregular structure were interspersed in the regions
      surrounding the cleavage sites. These data demonstrate the existence of conserved
      regions of thyroglobulin inherently sensitive to proteolysis, which most likely
      represent solvent-exposed regions of the primary structure, possibly forming
      loops at the surface of thyroglobulin.

PMID- 8269952
TI  - Evidence for a glycolipid anchor of gp64, a putative cell-cell adhesion protein
      of Polysphondylium pallidum.
AB  - The membrane-bound glycoprotein (gp64) of the cellular slime mold Polysphondylium
      pallidum, is a putative cell-cell adhesion protein identified by adhesion
      blocking antibody fragments. Since gp64 can be purified in a few days and in
      substantial yields, it is a good candidate for clarifying the structure of a cell
      cell adhesion protein. This study reveals that gp64 possesses a glycolipid anchor
      which is sensitive to deamination but resistant to phosphatidylinositol-specific
      phospholipase C from Bacillus thuringiensis. Although the anchor resistance to
      phosphatidylinositol-specific phospholipase C can be ascribed to the presence of
      an additional acyl chain on the inositol ring in the glycosyl
      phosphatidylinositol anchors, this was not the case. After a mild-base treatment
      that released an additional acyl chain on the inositol ring, only a trace amount
      of fatty acid was detected but, after strong acid hydrolysis, we detected both
      amide-linked fatty acids and a long-chain base. The long-chain base was further
      analysed by gas-chromatography/mass spectrometry and was found to be
      phytosphingosine. Both fatty acids and myo-inositol were also analysed by gas
      chromatography/mass spectrometry. These data suggest that gp64 possesses a
      glycolipid anchor which contains ceramide and myo-inositol.

PMID- 8269953
TI  - Characteristics of lysophospholipase activity expressed by cytosolic
      phospholipase A2.
AB  - Evidence has accumulated to suggest that a wide variety of mammalian cells and
      tissues express a cytosolic phospholipase A2 with arachidonoyl preference
      (cPLA2). Purified rabbit platelet-derived cPLA2, as well as the human recombinant
      enzyme originally identified in the monocytic leukemic cell line U937, exhibit
      significant lysophospholipase activity. Several series of experiments indicated
      that a single protein mediated both activities. Treatment of the purified enzyme
      with p-bromophenacylbromide or an anti-(rabbit platelet cPLA2) monoclonal
      antibody, RHY-5, suppressed the activity of phospholipase A2 without any
      appreciable effect on lysophospholipase activity, suggesting that the domain(s)
      required for phospholipase A2 activity may be located separately from that for
      lysophospholipase activity. Lysophospholipase activity was appreciably detected
      above the critical micellar concentration of the substrate.
      Lysophosphatidylcholine was also hydrolyzed efficiently when it was incorporated
      into liposomes made of dialkylphosphatidylcholine. The hydrolysis of
      lysophospholipid was dependent on the fatty acid bound at the sn1 position; the
      relative rates of hydrolysis of 1-oleoyllysophosphatidylcholine, 1
      palmitoyllysophosphatidylcholine, and 1-stearoyllysophosphatidylcholine were 23,
      8, and 1, respectively. A similar order of reactivity was observed with
      lysophospholipid incorporated into dialkylphosphatidylcholine liposomes. cPLA2
      may function not only as an arachidonate liberation enzyme but also as an enzyme
      responsible for degradation of certain molecular species of lysophospholipids
      formed in membranes.

PMID- 8269954
TI  - Specific hydrolysis of intact erythrocyte cell-surface glycosphingolipids by
      endoglycoceramidase. Lack of modulation of erythrocyte glucose transporter by
      endogenous glycosphingolipids.
AB  - This study represents the specific hydrolysis of cell-surface glycosphingolipids
      (GSLs) of intact cells by endoglycoceramidase (EGCase; EC.3.2.1.123) which
      cleaves the linkage between oligosaccharides and ceramides of various GSLs. After
      a 2-h incubation of horse intact erythrocytes with 20 mU EGCase II in the
      presence of activator at 37 degrees C, 68% of the N-glycolylneuraminic-acid
      containing ganglioside GM3(NeuGc) and 70% of 4-O-acetyl GM3(NeuGc) were found to
      be hydrolyzed without hemolysis, accompanied by a corresponding increase in
      ceramide but not sphingosine or N,N-dimethylsphingosine. No hydrolysis was
      observed for sphingomyelin, phosphatidylcholine, phosphatidylethanolamine,
      cholesterol or membrane proteins. The decrease in immunoreactivity with GMR8
      antibody, specific to NeuGc alpha 2,3Gal- of GM3(NeuGc), corresponded to that of
      cell-surface GM3(NeuGc) by the enzyme, and almost no immunoreactivity was found
      when 70% of the GM3(NeuGc) was hydrolyzed. Besides the cell-surface GM3(NeuGc) of
      horse erythrocytes, Gg3Cer of guinea pig, GM3(NeuAc) and LcCer of human, and
      bovine and rabbit erythrocyte IV3Gal alpha-nLc4Cer were found to be efficiently
      hydrolyzed by EGCase II even when present in intact cells, while human
      erythrocyte Gb4Cer is quite resistant to hydrolysis by the enzyme on the cell
      surface as well as in detergent micelles. Glucose incorporation via the glucose
      transporter in erythrocytes was not affected at all by the specific and
      exhaustive hydrolysis of cell-surface GSLs by EGCase II. This result strongly
      suggested that glucose transporter function was not directly modulated by
      endogenous GSLs. In summary, this paper demonstrates that, together with the
      assistance of activator protein, EGCase II will become a powerful tool for
      selectively removing sugar chains from cell-surface GSLs without damaging other
      cell membrane components, and will be useful for describing the biological
      functions of endogenous GSLs.

PMID- 8269955
TI  - Kinetics of endoglycoceramidase action toward cell-surface glycosphingolipids of
      erythrocytes.
AB  - As shown in the preceding paper [Ito, M., Ikegami, Y., Tai, T. & Yamagata, T.
      (1993) Eur. J. Biochem. 218, 637-643], endoglycoceramidase (EGCase; EC.3.2.1.123)
      was found to hydrolyze the cell-surface glycosphingolipids (GSLs) of erythrocytes
      without any damage to other cell membrane components. This paper represents the
      kinetics of EGCase action toward cell-surface GSLs of erythrocytes. Without
      activator or detergents, cell-surface GSLs were found to be hydrolyzed by EGCase
      II very slowly at pH 7.0. The initial reaction velocity of EGCase II under this
      condition was 0.038 pmol.min-1.mU-1 for horse erythrocyte cell-surface GM3 and
      0.032 pmol.min-1.mU-1 for guinea pig erythrocyte cell-surface Gg3Cer. The
      addition of activator protein (60 microM), which stimulates EGCase II in the
      absence of detergents, increased the initial reaction velocity of the enzyme 616
      fold for cell-surface GM3 and 468-fold for Gg3Cer, while no increased hemolysis
      was observed with the addition of activator. However, even in the presence of the
      activator, the cell-surface GSLs were very resistant to hydrolysis by EGCase II
      compared to GSL vesicles (or micelles) under same conditions. In contrast to the
      activator, Triton X-100 (0.4%, mass/vol.) not only stimulated the enzyme activity
      but also solubilized erythrocyte GSLs into detergent micelles, inducing further
      increment of the enzyme reaction velocity. The apparent Km and Vmax values of
      EGCase II were calculated from the Lineweaver-Burk plot as 47 microM and 35 pmol
      min-1 mU-1 for horse erythrocyte cell-surface GM3 and 44 microM and 27 pmol.min
      1.mU-1 for guinea pig erythrocyte cell-surface Gg3Cer, at pH 7.0 in the presence
      of activator at a concentration of 60 microM.

PMID- 8269956
TI  - Probing different conformational states of pregnancy-zone protein. Fluorescence
      studies utilizing the binding of 4,4'-bis(8-anilino-1-naphthalenesulphonate).
AB  - The binding of the fluorescence probe 4,4'-bis(8-anilino-1-naphthalenesulphonate)
      (bis-ANS) to the human proteinase inhibitor pregnancy-zone protein (PZP) and its
      complexes with methylamine and chymotrypsin were investigated. The existence of
      dimeric PZP-chymotrypsin complex was demonstrated and both the dimeric and the
      tetrameric PZP-chymotrypsin complexes could be studied separately. The
      fluorescence data indicate that bis-ANS binds to two different sites on PZP and
      its complexes. The values of the dissociation constant, Kd1, for the binding to
      the high-affinity site were determined to be 231 +/- 14, 220 +/- 28, 114 +/- 15
      and 49 +/- 1 nM, for the binding to native PZP, PZP-methylamine and dimeric and
      tetrameric PZP-chymotrypsin, respectively. An 11-30-fold decrease was observed in
      the affinity for the second site, the corresponding values of the dissociation
      constant, Kd2, being 1.5-2.8 +/- 1.0 microM, which are not significantly
      different for PZP and its derivatives. The results suggest that the probe bis-ANS
      discriminates between the different conformational states of PZP and that while
      the conformation of the complex with methylamine does not differ much from that
      of the native protein, there is a significant change in conformation when
      chymotrypsin cleaves the bait region. This is substantiated by a 30%-45% decrease
      in the maximum enhancement of fluorescence intensity when PZP is treated with
      chymotrypsin. Although the dimeric and tetrameric forms of PZP-chymotrypsin
      complexes differ in Kd1 values, the difference in the maximum enhancement of the
      fluorescence of bis-ANS by the two forms is not significant. This indicates that
      dimer-dimer interaction in the tetrameric form does not involve hydrophobic
      sites. The necessity of bait-region cleavage for extensive conformational changes
      in PZP distinguishes it from alpha 2-macroglobulin, the other alpha-macroglobulin
      in human plasma.

PMID- 8269957
TI  - Recombinant iron-regulatory factor functions as an iron-responsive-element
      binding protein, a translational repressor and an aconitase. A functional assay
      for translational repression and direct demonstration of the iron switch.
AB  - The translation of ferritin and erythroid 5-aminolevulinate synthase mRNAs is
      regulated via a specific high-affinity interaction between an iron-responsive
      element in the 5' untranslated region of ferritin and erythroid 5-aminolevulinate
      synthase mRNAs and a 98-kDa cytoplasmic protein, the iron-regulatory factor. Iron
      regulatory factor was expressed in vaccinia-virus-infected HeLa cells (hIRFvac)
      and in Escherichia coli (hIRFeco). An N-terminal histidine tag allowed a rapid
      one-step purification of large quantities of soluble recombinant protein. Both
      hIRFvac and hIRFeco bound specifically to iron-responsive elements and were
      immunoprecipitated by iron-regulatory-factor antibodies. Using in-vitro
      transcribed chloramphenicol-acetyltransferase mRNAs bearing an iron-responsive
      element in the 5' untranslated region, specific repression of chloramphenicol
      acetyltransferase translation by hIRFvac and hIRFeco was demonstrated in wheat
      germ extract. In addition, hIRFvac and hIRFeco were shown to display aconitase
      activity. Treatment of hIRFvac and hIRFeco with FeSO4 resulted in a drastic
      reduction in iron-responsive-element-binding of iron-regulatory factor, but
      caused a strong stimulation of its aconitase activity. The results establish that
      recombinant iron-regulatory factor is a bifunctional protein; after purification,
      it binds to iron-responsive elements and represses translation in vitro.
      Following iron treatment, iron-responsive-element binding is lost and aconitase
      activity is gained. No eukaryotic co-factor seems to be required for the
      conversion of the iron-responsive-element binding to the aconitase form of the
      protein.

PMID- 8269958
TI  - Nanomolar arachidonic acid influences the respiratory burst in eosinophils and
      neutrophils induced by GTP-binding protein. A comparative study of the
      respiratory burst in bovine eosinophils and neutrophils.
AB  - To investigate a possible role of phospholipase A2 (PLA2) in the respiratory
      burst in bovine eosinophilic and neutrophilic leukocytes dependent on GTP-binding
      protein (G-protein), we permeabilized these cells with Staphylococcus aureus
      alpha-toxin and induced NADPH oxidase activity with the non-hydrolysable GTP
      analogue GTP[S] or the aluminium tetrafluoro complex AlF4-. Under same
      experimental conditions, cells responded with different onset times. The onset
      time for eosinophils was 50-200 s, for neutrophils it was only a few seconds.
      GTP[S] stimulated in neutrophils only 5% of the respiratory burst compared to
      eosinophils, whereas AlF4(-)-induced comparable responses (neutrophils 120% of
      eosinophils). GDP inhibited these responses with an IC50 value of 2.4 mM.
      Arachidonic acid showed, with the exception of AlF4- stimulated neutrophils, on
      both stimuli and cell types an enhancing effect (150%) that reached its maximum
      at 0.1-1 microM. The PLA2 inhibitor 4-bromophenacylbromide reduced the GTP[S]-
      and AlF4(-)-induced response almost completely (10 microM) and the inhibition was
      not significantly different for eosinophils and neutrophils (IC50 1-3 microM). If
      the respiratory burst was reduced with 4-bromophenacylbromide to 1-4% of the
      original value, 10% of the basal NADPH oxidase activity could be restored by
      addition of only 20-100 nM arachidonic acid. In addition, the PLA2 activator
      adriamycin enhanced the response in a dose-dependent manner and in the same order
      as arachidonic acid did. The results presented above suggest that the respiratory
      burst may be regulated by different low-molecular-mass and/or heterotrimeric G
      proteins and an active role for arachidonic acid or its metabolites in the
      activation and the maintenance of the direct G-protein-stimulated respiratory
      burst in bovine eosinophils and neutrophils.

PMID- 8269959
TI  - Purification and characterization of a macromolecular-translocation inhibitor III
      of activated glucocorticoid-receptor-complex binding to nuclei from rat liver.
AB  - Macromolecular-translocation inhibitors (MTI) of binding of the activated
      glucocorticoid-receptor complex (GRC) to nuclei from rat liver are separated into
      at least three components (MTI-I-III) by DEAE-cellulose column chromatography
      [Okamoto, K., Isohashi, F., Horiuchi, M. & Sakamoto, Y. (1982) Biochem. Biophys.
      Res. Commun. 108, 1655-1660]. In this study, we have purified MTI-III from the
      livers of adrenalectomized rats to apparent homogeneity, as determined by
      SDS/PAGE. The purification procedure consisted of DEAE-cellulose chromatography,
      acid treatment and sequential chromatographies using gel filtration, S-Sepharose
      and Mono S columns. The purified protein had a molecular mass of approximately 69
      kDa, as estimated by SDS/PAGE, and the molecular mass of the inhibitor was
      approximately 68 kDa, as estimated by gel filtration. Thus, MTI-III exerts its
      inhibitory activity as a monomer. The sedimentation coefficient of MTI-III was
      approximately 3.7 S. Purified MTI-III was fairly stable at 4 degrees C but at
      higher temperatures, especially above 25 degrees C, it was rapidly inactivated.
      Under low-salt conditions, MTI-III was associated with activated GRC (4.2 S) and
      the resulting complex was detected on sucrose density gradients as a larger
      species (6.8 S). Initial treatment of nuclei or DNA-cellulose with MTI-III did
      not alter their abilities to bind activated GRC. These results indicate that MTI
      III acts through an interaction with GRC.

PMID- 8269960
TI  - PPQ, a novel protein phosphatase containing a Ser + Asn-rich amino-terminal
      domain, is involved in the regulation of protein synthesis.
AB  - The sequence of a Saccharomyces cerevisiae cDNA encoding a novel 61-kDa protein
      serine/threonine phosphatase, termed PPQ1, is presented. The protein consists of
      two distinct domains: the carboxy-terminal phosphatase domain is approximately
      60% identical to either PP1 or the carboxy-terminal domains of PPZ1 and PPZ2,
      while the amino-terminal region is rich in serine and asparagine. Deletion of the
      gene encoding PPQ1 reduces cell growth on several carbon sources, and lowers cell
      density in the stationary phase. Cells in which PPQ1 gene has been deleted show
      altered morphology from wild-type cells in the stationary phase in the absence of
      an essential amino acid and a reduced rate of protein synthesis in the
      exponential phase. They are hypersensitive to the protein synthesis inhibitors,
      cycloheximide and G418, implicating PPQ1 in the regulation of translation.

PMID- 8269961
TI  - Cloning and characterization of the poly(hydroxyalkanoic acid)-depolymerase gene
      locus, phaZ1, of Pseudomonas lemoignei and its gene product.
AB  - Four different DNA fragments each coding for poly(hydroxyalkanoic acid)
      depolymerase (phaZ1-phaZ4) were isolated in pUC plasmids from a genomic library
      of Pseudomonas lemoignei in Escherichia coli. All recombinant strains secreted a
      highly active poly(3-hydroxybutyric acid) depolymerase and produced large
      translucent halos on an opaque medium containing poly(3-hydroxybutyric acid)
      granules. One DNA region (phaZ1) was present in seven independently isolated
      clones. Three other cloned DNA fragments were different from phaZ1 and from each
      other (phaZ2-phaZ4). In phaZ1, an open-reading frame of 1245 bp was identified
      from the nucleotide sequence of a 5435-bp MboI fragment (57 mol G + C/100 mol) of
      this region and encoded a novel poly(hydroxyalkanoic acid) depolymerase of P.
      lemoignei, poly(3-hydroxybutyric acid) depolymerase C. A leader-sequence
      peptidase-cleavage site was predicted from the deduced amino acid sequence
      between Ala37 and Leu38. The calculated relative molecular masses of the
      precursor and the putative mature protein were 43468 and 39581, respectively. The
      polypeptide contains a lipase consensus sequence (Gly-Xaa-Ser-Xaa-Gly) and an
      unusually high proportion of threonine residues (22 of 36 amino acids) near the C
      terminus. The N-terminus of the deduced amino acid sequence of PhaZ1 differed
      from that of the purified poly(3-hydroxybutyric acid) depolymerases A, B and the
      poly(3-hydroxyvaleric acid) depolymerase of P. lemoignei. The phaZ1 gene product,
      poly(3-hydroxybutyric acid) depolymerase C, was partially purified from
      recombinant E. coli (pUC91::phaZ1). The purified protein was specific for
      poly(hydroxyalkanoic acid) consisting of monomers of four or five carbon atoms
      and for p-nithrophenylbutyrate as substrates. The polymer-hydrolyzing activity,
      but not the p-nitrophenylate esterase activity, was inhibited by complex media
      such as Luria-Bertani medium and by soluble E. coli proteins. The enzyme protein
      did not cross-react with antibodies raised against purified poly(3-hydroxyvaleric
      acid) depolymerase of P. lemoignei.

PMID- 8269962
TI  - Mutants of Methylobacterium extorquens and Paracoccus denitrificans deficient in
      c-type cytochrome biogenesis synthesise the methylamine-dehydrogenase
      polypeptides but cannot assemble the tryptophan-tryptophylquinone group.
AB  - Five mutants of Methylobacterium extorquens and four mutants of Paracoccus
      denitrificans that have a general defect in c-type cytochrome synthesis also
      failed to assemble an active methylamine dehydrogenase. In all cases methanol
      dehydrogenase, another periplasmic enzyme, was fully active. All nine mutant
      strains accumulated both the heavy and light subunits of methylamine
      dehydrogenase to essentially wild-type levels. In all nine mutants, the heavy
      subunit and light-subunit polypeptides were proteolytically processed, suggesting
      that translocation to the periplasm had occurred; in the case of the P.
      denitrificans mutants, a periplasmic location for the heavy and light subunits
      was confirmed experimentally. While specific quinone staining of the methylamine
      dehydrogenase light subunit in wild-type M. extorquens and P. denitrificans
      strains could readily be demonstrated, the light subunit polypeptides accumulated
      by the mutants did not quinone stain, indicating that the methylamine
      dehydrogenase prosthetic group, tryptophan tryptophylquinone, is not assembled in
      the absence of functional c-type cytochromes.

PMID- 8269963
TI  - Characterization of two glycosylated boar spermadhesins.
AB  - Boar spermadhesins AQN-1, AQN-3 and AWN form a recently described protein family,
      synthesized by the sexual accessory glands, and become associated with the sperm
      head upon ejaculation. They contain 109-133 amino acid residues, two conserved
      disulphide bridges, are not glycosylated, and have 40-60% primary structure
      identity. These boar polypeptides are multifunctional proteins, which possess
      heparin-, serine-protease-inhibitor- and/or zona-pellucida-glycoprotein-binding
      capability and have, therefore, been implicated in sperm capacitation and sperm
      oocyte attachment. AQN-2 (18-20 kDa), however, is unique among boar spermadhesins
      in that it is the only member of the family which is known to be glycosylated and
      which possesses weak zona-pellucida-binding but not seminal-plasma-inhibitor
      binding ability. In this study we report the structural and functional
      characterization of the two glycoproteins contained in the AQN-2 fraction. One
      component is identical with PSP-I, a major porcine seminal plasma protein whose
      function has not yet been identified, while the second protein is a glycosylated
      isoform of AQN-3. Here we show that the inability of the glycosylated boar
      spermadhesins to bind seminal-plasma protease inhibitors as well as the weak
      binding of glycosylated AQN-3 to zona pellucida glycoproteins is due to the
      presence of the oligosacharide chain on a conserved asparagine residue. This
      indicates that modification of a spermadhesin polypeptide framework may serve to
      modulate its ligand-binding capabilities.

PMID- 8269964
TI  - Kinetic characterization of the EcaI methyltransferase.
AB  - A kinetic analysis of the EcaI adenine-N6-specific methyltransferase (MTase) is
      presented. The enzyme catalyzes the transfer of a methyl group from S-adenosyl-L
      methionine (AdoMet) to the adenine of the GGTNACC sequence with a random rapid
      equilibrium mechanism. Experiments with a synthetic, 14-bp DNA substrate suggest
      that recognition of the specific site of DNA occurs after the binding of AdoMet.
      Proton concentration does not affect the dissociation constant of AdoMet while Vm
      and the dissociation constant of DNA show a maximum around pH 8. Increasing the
      amount of S-adenosyl-L-homocysteine decreases the inhibitory effect of methylated
      DNA which proves the active role of AdoMet in site recognition. Experiments with
      hemimethylated DNA show that the methylase binds the double-stranded DNA
      asymmetrically.

PMID- 8269965
TI  - Effect of proglycosyn and other phenolic compounds on glycogen metabolism in
      isolated hepatocytes. Potential role of glucuronidated metabolites.
AB  - The mechanism by which proglycosyn (LY 177,507) stimulates glycogen synthesis in
      isolated hepatocytes [Harris, R. A., Yamanouchi, K., Roach, P. J., Yen, T. T.,
      Dominiani, S. J. & Stephens, T. W. (1989) J. Biol. Chem. 264, 13674-13680] has
      been investigated. When incubated in the presence of hepatocytes, proglycosyn was
      metabolized to an O-demethylated glucuronidated derivative, as determined by fast
      atom-bombardment mass spectrometry and enzymic analysis. This metabolite
      accumulated almost linearly inside the cells to reach a concentration of
      approximately 3 mumol/g protein after 50 min, without apparent release into the
      medium. In confirmation of previous work, proglycosyn decreased the level of
      phosphorylase a and increased that of synthase a in hepatocytes. Washing of cells
      incubated with proglycosyn for 30 min considerably decreased the concentration of
      the drug without significantly modifying the intracellular concentration of the
      metabolite and the activation state of glycogen synthase. Several compounds
      bearing structural analogy with proglycosyn were also tested for their effect on
      glycogen metabolism. At millimolar or submillimolar concentrations, resorcinol, m
      anisidine, phenol, 3-hydroxyacetophenone, and 3-acetamidophenol, although not 4
      acetamidophenol, stimulated the incorporation of [14C]glucose into glycogen,
      decreased the level of phosphorylase a and increased the level of synthase a. In
      the case of phenol, the effect on the glycogen enzymes paralleled the
      intracellular accumulation of phenylglucuronide. Furthermore, ethanol and D
      galactosamine, which decreased the conversion of phenol to phenylglucuronide and
      the intracellular concentration of phenylglucuronide, counteracted the effect of
      phenol on the synthase and on the phosphorylase. From these results, it is
      suggested that the effect of proglycosyn and of simpler phenol derivatives is
      mediated by glucuronidated metabolites, which act on an intracellular target.

PMID- 8269966
TI  - Formation of diacylglycerol, inositol phosphates, arachidonic acid and its
      metabolites in macrophages.
AB  - Treatment of macrophages with zymosan, 4 beta-phorbol 12-myristate 13-acetate
      (PMA) and fluoride but not with A 23187 or arachidonic acid (delta Ach) leads to
      a generation of diacylglycerol (acyl2Gro). Formation of inositol phosphates is
      achieved with zymosan, only. An elevation of intracellular calcium is obtained
      with zymosan and A 23187 but not with PMA, fluoride or delta Ach. Prior treatment
      of the cells with phorbol ester for 3 h which has been shown recently to result
      in a down-regulation of protein kinase (PK) C-beta but not PKC-delta [Duyster,
      J., Schwende, H., Fitzke, E., Hidaka H. & Dieter P. (1993) Biochem. J. 292, 203
      207] has no effect on the zymosan-induced formation of acyl2Gro or inositol
      phosphates but inhibits the PMA-induced generation of acyl2Gro. Down-regulation
      of PKC-delta by prior phorbol ester treatment for 24 h augments the zymosan
      induced generation of acyl2Gro and inositol phosphates. The acyl2Gro lipase
      inhibitor RG 80267 inhibits the PMA-induced and fluoride-induced generation of
      prostaglandin (PG) E2, reduces the zymosan-induced release of PGE2 by 50% but has
      no effect on PGE2 formation of unstimulated, A 23187-treated or delta Ach-treated
      cells. Furthermore, RG 80267 enhances accumulation of delta Ach-labeled acyl2Gro
      in response to zymosan, PMA and fluoride. These data indicate that zymosan
      activates a phosphatidylinositol 4,5-bisphosphate-specific phospholipase (PL) C,
      that generation of acyl2Gro by PMA and fluoride occurs via hydrolysis of other
      phospholipids, that PKC-beta is involved in the PMA-induced generation of
      acyl2Gro and PKC-delta negatively modulates the zymosan-induced activation of PLC
      and PMA and fluoride induce a liberation of delta Ach from acyl2Gro, A 23187
      activates the PLA2 pathway and zymosan stimulates both, the acyl2Gro- and PLA2
      pathway.

PMID- 8269967
TI  - Analysis of nucleo-cytoplasmic transport in a thermosensitive mutant of nuclear
      pore protein NSP1.
AB  - NSP1 is related to a group of nuclear pore proteins termed 'nucleoporins'. We
      observe that in thermosensitive nsp1 mutants lacZ fusion proteins which contain
      the nuclear targeting sequence of Mat alpha 2 or Pho2 are located inside the
      nucleus at the permissive temperature (23 degrees C), but are mislocalized in the
      cytoplasm at the restrictive temperature (37 degrees C). No evidence was obtained
      that the large lacZ reporter protein leaks out from the nucleus. Another nuclear
      passenger protein consisting of the NLS of ribosomal protein L25 and cytosolic
      dihydrofolate reductase (DHFR) is also accumulating in the cytoplasm after
      shifting ts nsp1 cells to 37 degrees C. In the latter case, this could be
      attributed to an increased leakage of the reporter protein from the nucleus into
      the cytoplasm. These data suggest that NSP1 mutation affects nuclear transport
      and nuclear retention, but the effects depend on the used NLS and the reporter
      protein.

PMID- 8269968
TI  - Evidence for the presence of alpha and beta-related T3 receptors in rat liver
      mitochondria.
AB  - Although the dependence of mitochondrial structure and function on thyroid
      hormone status is well established, several attempts to demonstrate a direct
      pathway of T3 action on mitochondria have been made during the last decade
      without being firmly conclusive. In this study, we present evidence firstly for
      the presence of specific binding sites for [125I]-T3 in rat liver mitochondria 5
      min after injection, as assessed by ultrastructural autoradiography. In the same
      way, using immunocytological techniques and protein immunoblotting, T3 receptor
      like immunoreactivity was revealed mainly in the nucleus and mitochondria of
      hepatocytes. Whereas the colloidal gold labeling over mitochondria was found to
      be specific at the ultrastructural level, these results were confirmed
      biochemically by Western blotting experiments which revealed the presence of two
      protein bands in mitochondria: a stronger one of 55 kDa and a weaker one of 48
      kDa. At the opposite, receptor T3 mRNAs were not detected in mitochondria by
      ultrastructural in situ hybridization thus confirming that the synthesis of
      receptor T3 occurs in the cytoplasm and that nuclear-encoded T3 receptors may
      belong to the bulk of cytosolic precursor polypeptides which are targeted to and
      imported into mitochondria. These results confirm that a direct pathway of T3
      action on mitochondria occurs in situ which could now explain how the rapid
      activation of several mitochondrial functions can take place within minutes after
      thyroid hormone injection.

PMID- 8269969
TI  - The transferrin receptor in African trypanosomes: identification, partial
      characterization and subcellular localization.
AB  - All eukaryotic cells, including African trypanosomes, require iron for growth and
      division, and this iron is acquired by the receptor-mediated endocytosis of iron
      loaded transferrin (diFe(3+)-transferrin). In trypanosomes transferrin (Tf) has
      been shown to be delivered into lysosomes and may not recycle back to the cell
      surface as it does in mammalian cells (Grab, D. J., et al., Eur. J. Cell Biol.
      59, 398-404 (1992)). Here, we describe for the first time, the characteristics of
      a Tf-binding protein with receptor-like properties in Trypanosoma brucei brucei.
      Bloodstream forms of rodent-adapted T. brucei were incubated with [35S]methionine
      and detergent lysates chromatographed on a Sephacryl S-300 column. Fractions were
      incubated with anti-Tf serum to immunoprecipitate Tf/Tf-binding protein
      complexes. On sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE) the molecular mass of the major protein in the immunoprecipitate was 88 to
      92 kDa. Tf-binding proteins could also be isolated using diferric Tf-Sepharose.
      The molecular mass of the major Tf-binding protein, as estimated from Sephacryl S
      300 column chromatography, in the presence of detergent, was approximately 90 to
      100 kDa and 90 kDa with SDS-PAGE. Each 90 kDa Tf-binding protein was able to bind
      one molecule of diferric Tf. Since monoclonal antibodies to human and bovine Tf
      receptors failed to react with any trypanosome proteins, antisera were raised
      against the T. brucei Tf-binding proteins eluted from Tf-Sepharose at low pH.
      These antibodies recognized a 90 kDa protein on Western blots of a T. brucei
      lysate and inhibited the growth of T. brucei in vitro. Immunolocalization
      studies, using this antiserum showed that the Tf-binding protein was localized in
      the flagellar pocket and within the early endosomal compartments. In the presence
      of protease inhibitors there was additional localization in lysosome-like
      organelles. The Tf-binding characteristics and localization of this 90 kDa
      protein suggest that this molecule is a strong candidate as a physiological
      receptor for Tf in these parasites.

PMID- 8269970
TI  - Inhibition of intracellular transport of newly synthesized prolactin by
      bafilomycin A1 in a pituitary tumor cell line, GH3 cells.
AB  - We have investigated the effects of bafilomycin A1, a specific inhibitor of
      vacuolar type H(+)-ATPase, on the secretion and intracellular distribution of
      prolactin in cultured rat pituitary tumor cells (GH3 cells). Pulse-labeling the
      cells with L-[35S]methionine for 5 min and subsequently incubating in chase
      medium containing 1 microM bafilomycin A1 showed inhibition of basal secretion of
      labeled prolactin. The inhibition of the secretion by the drug was clearly
      observed when it was added within 7.5 min after the pulse-labeling, whereas
      inhibition was barely observed when added at 22 min. When the pulse-labeled cells
      were chased with 1 microM bafilomycin A1 for 1 h and then washed and incubated in
      the presence of 10 micrograms/ml brefeldin A (BFA) for 2 h, BFA barely affected
      the secretion during the latter 2 h period. This result suggested that the
      labeled prolactin had passed through a BFA-sensitive step(s) in the intracellular
      transport during the treatment with 1 microM bafilomycin A1. Immunofluorescence
      microscopy and immunogold electron microscopy revealed that, when the cells were
      incubated with 0.1 to 1.0 microM bafilomycin A1, small, dense secretory granules
      containing prolactin decreased markedly, and numerous large vacuoles appeared,
      which also contained prolactin, and were partially coated with clathrin-like
      materials. The Golgi apparatus itself was preserved except for some dilatation of
      the trans-Golgi cisternae and trans-Golgi network (TGN) where these vacuoles were
      likely to be formed. These results suggest that acidification in immature
      secretory granules generated by a vacuolar type H(+)-ATPase is necessary for the
      intracellular transport of prolactin, maturation and concentration processes of
      the secretory granules.

PMID- 8269971
TI  - The amino terminus of mammalian nucleolin specifically recognizes SV40 T-antigen
      type nuclear localization sequences.
AB  - Nucleolin is a major nucleolar protein in mammalian cells that is thought to be
      involved in ribosome biogenesis. The discovery that nucleolin shuttles between
      the cytoplasm and the nucleus raises the possibility that it is also involved in
      transporting ribosomal or nuclear proteins to the nucleus. The three structural
      domains of nucleolin bear a striking resemblance to the domains of a previously
      identified yeast protein NSR1, although the two proteins do not share a high
      degree of sequence similarity. NSR1 specifically recognizes the nuclear
      localization sequence (NLS) of both the simian virus large T antigen (SV40 T
      antigen) and the yeast histone H2B by ligand blot analysis, and is a candidate
      for a receptor involved in the initial stages of nuclear transport. We report
      here that nucleolin, either purified from Chinese hamster ovary (CHO) cells or
      expressed in yeast, also specifically recognizes the wild-type, but not a mutant,
      histone H2B nuclear localization sequence by ligand blot analysis. The NLS
      recognition site is located within the N-terminal domain of both proteins. In
      showing that nucleolin, a protein that moves between the cytoplasm and the
      nucleus, also has the ability to interact with nuclear localization signals, our
      data support the idea that shuttling nucleolar proteins play a role in nuclear
      transport.

PMID- 8269972
TI  - Highly polarized primary epithelial cells from human nasopharynx grown as
      spheroid-like vesicles.
AB  - The value of experimental culture models using epithelial cells often depends on
      the degree of polarization and other critical features observed in natural
      tissues, including the formation of tight junctions, desmosomes and membrane
      interdigitations. However, growth of normal epithelial cells as monolayers on
      artificial supports also leads to partial loss of the original characteristics of
      epithelial cells, and the quality of the monolayer is strongly influenced by the
      physicochemical properties of the support. In addition, not all normal epithelial
      cell types are able to adhere and to grow well on artificial substrata. In order
      to circumvent the drawbacks of two-dimensional cultures we established an in
      vitro model that closely resembles the in vivo situation of the intact
      epithelium. Human epithelial cells from nasopharynx (HNPEC) were used to prepare
      multicellular epithelial vesicles consisting of both non-ciliated and ciliated
      mucosal cells. Electron microscopy investigations showed that the morphological
      appearance of the epithelial cells was similar to that in situ. HNPEC vesicle
      cultures maintain a geometrically intact organization of individual cells that is
      not achieved using conventional culture conditions. HNPEC vesicles are more in
      vivo-like than two-dimensional cultures and therefore represent a suitable model
      for a variety of research purposes including studies on the pathogenesis of
      invasive microorganisms.

PMID- 8269973
TI  - Epithelioid and fibroblastic cell lines derived from the ileum of an adult
      histocompatible miniature boar (d/d haplotype) and immortalized by SV40 plasmid.
AB  - Intestinal explants were maintained for weeks in a growth medium containing
      collagenase for progressive digestion to derive finite cell lines from the ileum
      (64 lines) or from the colon (8 lines) of a boar. Two ileal cell lines retaining
      either a fibroblastic or an epithelioid morphology have been used to derive
      heteroploid cell lines (IPI-1 and IPI-2) immortalized by transfection with an
      SV40 plasmid (pSV3-neo). The IPI-1 cells were found of fibroblastic lineage. The
      IPI-2 cell line gave rise to morphologically heterogeneous colonies ranging from
      typical epithelial cells to colonies of more-elongated cells. A crisis occurred
      during subcultivation of IPI-2 leading to the isolation of the IPI-2I cell line
      with a 24 h doubling time and a 21% plating efficiency. Epithelial nature of IPI
      2I cells was supported by ultrastructural analysis of the cell monolayers.
      Differentiated cells were found to express microvilli at the apical cellular
      membrane and desmosomes connecting adjacent cells. Stable epithelioid phenotypes
      were obtained only from the IPI-2I cell line by multiple subcloning. These cells
      were found to express characteristics of both epithelial and mesenchymal cells by
      positive immunostaining with monoclonal antibodies reacting either with keratin
      18 filament of simple epithelia or with vimentin filament typical in vivo of
      mesoderm. The lack of villin expression and the absence of transepithelial
      resistance have to be related to a poor differentiated state of this cell line.
      All these immortalized cell lines were permissive to the replication of
      microorganisms pathogenic for pig (Salmonella chloleraesuis, Salmonella
      typhimurium and tissue culture-adapted strains of transmissible gastroenteritis
      virus). The collection of finite and continuous cell lines will help to develop
      in vitro methods for long-term propagation of freshly isolated epithelium or
      three-dimensional organ culture in pig. In addition, the IPI-2I cell line
      provides a new model to study the conversion from a transformed to a
      nontransformed phenotype as incorporation of 2% dimethyl sulfoxide in the growth
      medium to repress large tumor antigen expression led to the progressive
      disappearance of cytokeratin 18 positive cells with, over a week, the death of
      the surviving vimentin-positive cells.

PMID- 8269974
TI  - Malignant cells have increased levels of common glycoprotein ligands of the
      endogenous cerebellar soluble lectin CSL.
AB  - The glycoprotein composition of various transformed cells or malignant tumors was
      analyzed and compared to their respective non-malignant control cells or tissues
      of several species, including man, using an endogenous carbohydrate-binding
      protein, the cerebellar soluble lectin CSL (Zanetta et al., J. Neurochem. 49,
      1250-1257 (1987). A large variety of transformed cells contain a much higher
      number and larger quantity of glycoprotein ligands of CSL than the control cells
      or normal tissues. The glycoprotein profiles were, in most cases, independent of
      the nature of the cell transformation of the degree of differentiation, of the
      tissue and species. Thus, it is suggested that many transformed cells have, as a
      common anomaly, the increased synthesis of the special type of glycan recognized
      by CSL, expressed on the same polypeptide chains.

PMID- 8269975
TI  - Duchenne muscular dystrophy: lack of differences in the expression of endogenous
      carbohydrate- and heparin-binding proteins (lectins) in cultured fibroblasts.
AB  - Duchenne muscular dystrophy (DMD), the most severe form of inherited muscular
      dystrophies, is known to be caused by a deficiency of the protein "dystrophin",
      but the pathophysiologic consequences of this lack have not as yet been
      elucidated. Investigations with cultured fibroblasts point to altered adhesion
      mechanisms in cells from DMD patients. Because endogenous carbohydrate-binding
      proteins (lectins) play an important role in cell-cell and cell-matrix
      interactions and therefore might be involved in these alterations, we separated
      such proteins with specificities for beta-galactosyl-, alpha-mannosyl-, and alpha
      glucosyl-residues, as well as heparin-binding proteins from cultured fibroblasts.
      Owing to enormous interindividual variations among DMD patients and among healthy
      controls our hypothesis could not be confirmed. In the course of the experiments
      we could detect a growth-related binding of heparin to nuclei of cells from DMD
      patients and healthy controls restricted to rapidly growing cultures and
      telophases of mitoses, but not in contact-inhibited monolayers. This finding
      suggested a possible involvement of the cellular ligand in growth control and
      coincided with the occurrence of basic fibroblast growth factor.

PMID- 8269976
TI  - Nucleoplasmin uptake by facilitated transport and intranuclear binding.
AB  - Specific proteins are selectively translocated into the cell nucleus and
      accumulated therein, but the molecular mechanisms underlying this fundamental
      eukaryotic transport process remain obscure. We have employed a new experimental
      system with notable advantages for resolving protein translocation and
      accumulation mechanisms. Individual nuclei are isolated from oocytes under
      mineral oil and conjoined under the oil with either an aqueous bead or a similar
      volume of oocyte cytoplasm to form closed transport pairs. Using these pairs one
      can (i) present transportant proteins via the bead or cytoplasm to a minimally
      disturbed nucleus, (ii) monitor the intactness of the nuclear envelope, and (iii)
      separate pairs at various times after formation and measure the amount of
      transportant in each compartment. In addition, it is uniquely possible with these
      pairs to determine whether or not a transportant's concentration gradient
      constitutes a chemical activity gradient. This is done by puncturing the
      envelope, thus eliminating its normal sieving restrictions on diffusion, and
      measuring the effect on the transportant distributions. We demonstrate that a
      prototypical nuclear-accumulating protein, nucleoplasmin (Np), is translocated
      through the nuclear pore complex by a mechanism of facilitated transport, rather
      than active transport. We further show that Np's high accumulation results from
      subsequent intranuclear binding. Np's facilitated transport and intranuclear
      binding are both ATP-dependent, and the latter requires cytoplasmic protein(s).

PMID- 8269977
TI  - Characterization of cardiotin, a structural component in the myocard.
AB  - The characterization and subcellular distribution of cardiotin, a structural
      component of striated muscle, is described using a monoclonal antibody. This high
      molecular mass component (> 300 kDa) is expressed in the myocard of several
      species and to a lesser extent also in skeletal muscle. Cardiotin is not found in
      smooth muscle tissues, other mesenchymal or epithelial tissues. The cardiotin
      distribution pattern is independent of other sarcomeric components, such as
      desmin, myosin, actin, titin, nebulin, and desmoplakin, and shows a longitudinal
      filamentous localization between myofibrils. The average distance between
      parallel running cardiotin filaments is approximately 2.3 microns, as concluded
      from confocal scanning laser microscopic analysis of double-immunolabeled muscle
      preparations. The cardiotin filamentous staining reaction is oriented
      perpendicularly to the typical cross-striations observed with antibodies to
      desmin, spanning several sarcomeres and showing a length between 12 to 80 microns
      in frozen sections. Its localization pattern suggests a possible link with the
      sarcoplasmic reticulum. We have never observed cardiotin filaments to cross the
      intercalated disks, stained by antibodies to desmoplakins or desmin. Cardiotin
      cannot be solubilized from cardiac muscle by nonionic detergents of high
      concentrations of KCl or KI, suggesting a structural role in the myocard. The
      protein could so far not be detected in developing embryonic heart, but
      expression seems to be initiated after birth, depending on the species examined.

PMID- 8269978
TI  - Actin dynamics in human neutrophils during adhesion and phagocytosis is
      controlled by changes in intracellular free calcium.
AB  - The role of changes in cytosolic free calcium concentration ([Ca2+]i) in the
      assembly and disassembly of actin during adhesion and phagocytosis was evaluated.
      Rhodamine-phalloidin staining combined with quantitative fluorescence and
      confocal laser scanning microscopy was used to measure local F-actin changes in
      single adherent human neutrophils phagocytosing yeast particles on different
      surfaces and under different calcium conditions. Cells were suspended in a)
      calcium-containing medium (CCM) or b) calcium-free medium (CFM) or c) were first
      depleted of calcium (i.e., MAPT/AM-loaded in CFM) and then suspended in CFM
      (MAPT). In parallel, local [Ca2+]i changes were monitored using a fura-2 ratio
      imaging system. In CCM or CFM, attachment to the substrate and formation of
      pseudopods around a yeast particle generated, within a few seconds, rises in
      [Ca2+]i, both around the phagosome and in the cell body. During continued
      phagocytosis, [Ca2+]i was more elevated around the phagosome compared to the rest
      of the cell. No [Ca2+]i fluctuations were observed in MAPT cells. Adhesion and
      phagocytosis led to a several-fold increase in F-actin. The increase was
      transient in cells in CCM and CFM, but remained high in Ca-depleted neutrophils.
      A distinct ring of F-actin was formed around a phagosome with a yeast particle.
      Twenty min after ingestion the amount of this actin decreased more than 50% in
      CCM and CFM cells but increased by 40 to 100% in MAPT cells. The accumulation of
      F-actin in MAPT cells was reduced to resting levels by adding Ca2+ and ionomycin
      after ingestion. This treatment reestablished the periphagosomal [Ca2+]i rises,
      as observed in CCM cells. In conclusion, the present study shows that the actin
      polymerization, occurring in human neutrophils during adhesion and phagocytosis,
      is not influenced by changes in [Ca2+]i, whereas the subsequent depolymerization
      is. The accumulation of actin filaments around the phagosome in calcium-depleted
      cells could be involved in the inhibition of phagolysosome fusion seen in the
      absence of [Ca2+]i changes (Jaconi et al., J. Cell Biol. 110, 1555-1564 (1990)).
      This suggests that the actin network, controlled by [Ca2+]i, regulates the
      movement of granules during phagocytosis.

PMID- 8269979
TI  - Phosphorylation of vimentin in the C-terminal domain after exposure to calyculin
      A.
AB  - Exposure of 3T3 fibroblasts to the phosphatase inhibitor, calyculin-A, induces
      marked morphological changes and the formation of an aggregate of actin and
      myosin connected to the nucleus by intermediate filaments (Hirano, K., L.
      Chartier, R. G. Taylor, R. E. Allen, N. Fusetani, H. Karaki, D. J. Hartshorne: J.
      Muscle Res. Cell Motil. 13, 341-353 (1992)). Vimentin was isolated from this
      complex and shown to be phosphorylated. At least 4 phosphorylation sites were
      indicated. These sites were distinct from those phosphorylated by the cAMP
      dependent protein kinase. Limited proteolysis was used to define the domains in
      which phosphorylation occurred. Vimentin was isolated from 32P-labeled calyculin
      A-treated cells and digested with thrombin and alpha-chymotrypsin. Proteolysis
      with thrombin limited the phosphorylation to either the central core or C
      terminal domain. Proteolysis with alpha-chymotrypsin indicated that the multiple
      phosphorylation sites were restricted to the C-terminal domain of vimentin.

PMID- 8269980
TI  - An 18-bp element in the 5' untranslated region of the Drosophila beta 2 tubulin
      mRNA regulates the mRNA level during postmeiotic stages of spermatogenesis.
AB  - During Drosophila spermatogenesis transcriptional activity is mainly restricted
      to premeiotic stages. Translation during sperm morphogenesis, however, proceeds
      for several days, requiring a high stability for mRNAs translated
      postmeiotically. We studied expression of the Drosophila beta 2 tubulin gene,
      which is expressed solely in the male germ line from the primary spermatocyte
      stage onwards. Cis-acting elements involved in the regulation of mRNA levels were
      investigated in transgenic fly strains. In adult testes, mRNA amounts from beta 2
      lacZ fusion genes in the presence of an 18-bp AT-rich element, termed beta 2DE1,
      are elevated about threefold. The element is present at about the same position
      in the 5' untranslated regions of the beta 2 tubulin genes of the distantly
      related species Drosophila melanogaster and Drosophila hydei. Changing the
      position of the element on the mRNA reduces the stabilizing effect, while
      inversion of the beta 2DE1 abolishes its function. The element also acts in a
      combination with the beta 1 tubulin transcription start site, and the beta 2UE1,
      which is required to achieve tissue-specific expression. In all experiments done,
      the comparison of premeiotic with postmeiotic stages strongly implies that this
      element is involved in regulating mRNA stability. This mRNA stabilizing element
      acts in a position-independent manner and also on a heterologous mRNA, showing
      its autonomous functional activity.

PMID- 8269981
TI  - Microtubules regulate the generation of polarity in zoospores of Phytophthora
      cinnamomi.
AB  - Zoospores of Phytophthora cinnamomi are formed by cleavage of a multinucleate
      sporangium and contain nine different components that are distributed or oriented
      about a well-defined axis running through a pair of basal bodies near the
      nucleus. In this study, the importance of the cytoskeleton in establishing and
      maintaining cellular polarity was examined by using the anti-microtubule drug
      oryzalin and the anti-microfilament drug cytochalasin D (CD). The effects of the
      drugs on uncleaved and cleaving sporangia were determined, using fluorescence
      microscopy, for six of the components that are polarized in untreated cleaved
      cells: an astral microtubule (MT) array, the nucleus, mitochondria and three
      different types of vesicles, two of which are involved in directed exocytosis. CD
      had no effect upon the MT arrays, the positioning of nuclei or the polarized
      redistribution of mitochondria and vesicles to the cortical cytoplasm, although
      it did cause abnormal cleavage. The effects of oryzalin, however, indicate that
      the asymmetric disposition of the MT array is fundamental to zoospore polarities:
      when the array is itself eliminated with this drug, none of the other five
      elements show any signs of polar positioning within the cleaved sporangium.
      Oryzalin also caused abnormal cleavage similar to that seen in CD-treated cells.
      Most intriguing, however, was the finding that although the three vesicle types
      in cleaved, oryzalin-treated sporangia did not exhibit the polarized distribution
      seen in control and CD-treated cells, in many cases the vesicles had,
      nevertheless, lost their initially random distributions and had become
      concentrated in the cytoplasm adjacent to the abnormal cleavage planes. Thus
      although an intact MT array is required for segregation of the vesicles within
      the cortex, their redistribution to the cortex can somehow occur in the absence
      of MTs and actin microfilaments.

PMID- 8269982
TI  - Distribution of integrin subunits on rat metaphyseal osteoclasts and osteoblasts.
AB  - A key event in bone resorption is the attachment of osteoclasts to the bone
      matrix. The process apparently involves integrin plasma membrane receptors for
      extracellular matrix proteins. In the present study the distribution of some
      integrin subunits among different osteoclastic and osteoblastic domains was
      determined using immunocytochemistry on rat metaphyseal bone. Ultrathin
      cryosections were incubated with polyclonal antibodies against the alpha v beta 3
      integrin and against the individual integrin subunits, alpha v, beta 1, beta 3,
      and beta 5. Bound antibodies were detected with 10-nm colloidal gold coated with
      protein A. The results show that alpha v- and beta 3-subunits are enriched at the
      osteoclast plasma membrane facing the bone matrix, i.e., the clear zone.
      Furthermore, beta 1- and beta 5-subunits were somewhat enriched at the osteoblast
      plasma membrane facing the bone surface. The present observations corroborate and
      extend our previous data indicating that the alpha v beta 3 integrin mediates
      tight attachment of the osteoclast to the bone matrix. Moreover, a role for
      integrins in the attachment and interactions of the osteoblast is suggested.

PMID- 8269983
TI  - Thyroperoxidase mRNA in quiescent and proliferating thyroid epithelial cells:
      expression and subcellular localization studied by in situ hybridization.
AB  - Using in situ hybridization procedure, we have investigated the regulation and
      the cellular localization of thyroperoxidase (TPO) messenger RNA accumulation as
      a marker of differentiation in dog thyroid epithelial cells in primary culture.
      The response to different mitogens (TSH acting through cAMP, EGF and TPA) has
      been compared. TPO mRNA accumulation was exquisitely dependent on a continuous
      TSH/cAMP stimulation. It was induced within 1 h in the whole cell population from
      a very low basal level. This effect was inhibited by the cAMP-independent
      mitogens EGF and TPA. By contrast, the TSH-induction of TPO mRNA accumulation was
      observed irrespectively of the proliferative activity of the cells, i.e. in the
      presence or the absence of insulin, which is required for mitogenesis. The short
      half-life of TPO mRNA (+/- 2 h) implies that it was continuously transcribed
      during TSH/cAMP-dependent cell cycling. As compared to another thyroid
      differentiation marker, thyroglobulin mRNA (Pohl et al., J. Cell Biol. 111, 663
      672 (1990)), TPO mRNA accumulation differed by the rapidity of its control by
      cAMP, the pattern of its intercellular heterogeneity, and the unexpected
      segregation to a perinuclear region, probably the nuclear envelope that
      constitutes a specialized part of the endoplasmic reticulum. Despite these
      differences, both TPO and thyroglobulin gene transcriptions are unequivocally
      compatible with the cell cycle when induced by cAMP, at variance with the
      generally observed antagonism between growth and differentiation expression.

PMID- 8269984
TI  - Enhanced endothelial cell retraction mediated by 12(S)-HETE: a proposed mechanism
      for the role of platelets in tumor cell metastasis.
AB  - Platelets have been hypothesized to contribute to tumor cell metastasis, but the
      underlying mechanism(s) remain unknown. We demonstrate here that one mechanism
      whereby platelets may facilitate metastasis is by potentiating tumor cell-induced
      endothelial cell retraction, a prerequisite for the extravasation of most tumor
      cell types. The integrity of cultured microvascular endothelial cell (CD3 cells)
      monolayers was perturbed by 12[S]-hydroxyeicosatetraenoic acid (12(S)-HETE), a
      lipoxygenase metabolite of arachidonic acid, as well as by tumor cells (i.e.,
      Lewis lung carcinoma cells or 3LL). 3LL cells induced a concentration- and time
      dependent retraction of the CD3 monolayers, as assessed by quantitative binding
      assays as well as by phase-contrast microscopy. In contrast, normal murine
      fibroblasts (3T3) did not induce endothelial cell retraction. 3LL cell-induced
      endothelial cell retraction was potentiated, in a dose- and time-dependent
      manner, by homologous murine platelets while platelets alone did not induce
      endothelial cell retraction. Platelet-enhanced, tumor cell-induced endothelial
      cell retraction was inhibited by treating either tumor cells or platelets with
      the lipoxygenase inhibitors nordihydroguaiaretic acid or N-benzyl-N-hydroxy-5
      phenylpentanamide (BHPP) as well as by PGI2 or its analogs iloprost and ZK96.480
      (cicaprost), but not by the cyclooxygenase inhibitor aspirin (ASA). Tumor cells,
      upon adhesion to endothelium, initiated 12(S)-HETE biosynthesis, which was
      inhibited by pretreating tumor cells with BHPP but not with ASA. Additionally,
      12(S)-HETE biosynthesis during tumor cell-endothelial cell adhesion was
      significantly enhanced by the addition of homologous platelets. Collectively,
      these results suggest that tumor cell-platelet-endothelial cell interactions lead
      to enhanced biosynthesis of 12(S)-HETE by tumor cells and/or platelets, which in
      turn induces endothelial cell retraction, thus facilitating tumor cell
      extravasation and metastasis.

PMID- 8269985
TI  - Commitment to cell death is signaled by the appearance of a terminin protein of
      30 kDa.
AB  - Programmed cell death appears to be regulated by a specific molecular program,
      often dependent upon the activation of unique genes. We have identified terminin
      in the 60-kDa form as the unique subspecies present only in senescent human
      diploid fibroblasts. In this report, the biochemical properties of terminin
      during the process of induced cell death in Swiss 3T3 cells is investigated by
      total removal of serum, which subsequently activates apoptosis as determined by
      DNA degradation. Evidence presented here indicates that a specific proteolytic
      cleavage of terminin proteins occurs during apoptosis, leading to the appearance
      of a protein species with a molecular mass of 30 kDa (Tp-30) in serum-deprived
      mouse 3T3 cells. The appearance of Tp-30 can be modulated up to 24 h after serum
      deprivation by pretreatment with cycloheximide or returning to serum-containing
      conditions. These studies thus define the association of apoptosis-specific
      proteolysis of terminin and the appearance of Tp-30 with cell death in mouse 3T3
      fibroblasts and can serve as a marker for cells on their way to apoptosis.

PMID- 8269986
TI  - Control of mammary epithelial cell DNA synthesis by epidermal growth factor,
      cholera toxin, and IGF-1: specific inhibitory effect of prolactin on EGF
      stimulated cell growth.
AB  - Epidermal growth factor (EGF) stimulates mouse mammary cell proliferation in
      vivo, but its maximal level in the mammary gland is at midlactation, when little
      mammary growth takes place. The present studies use a normal murine mammary gland
      epithelial cell line (NMuMG) to determine the effects of the mammary mitogens
      EGF, cholera toxin (CT), and insulin-like growth factor-1 (IGF-1) on cell
      proliferation and how cell growth is altered by addition of the lactogenic
      hormone prolactin (PRL). EGF and CT stimulated over a fourfold increase of DNA
      synthesis in NMuMG cells when compared to basal levels. Only a twofold
      stimulation of DNA synthesis was observed when cells were treated with IGF-1.
      There was a slight increase in the percentage of cells in S-phase when these
      agents were added in combination with each other. Physiological levels of PRL had
      no significant effect on CT- or IGF-1-induced DNA synthesis but reduced EGF
      stimulated cell proliferation to basal levels. Furthermore, PRL reduced the
      percentage of cells in S-phase to IGF-1- and CT-induced levels in the presence of
      EGF. Interestingly, PRL increased cellular levels of EGF mRNA after 2 h of
      treatment, which is similar to the response of mouse mammary glands cultured in
      lactogenic hormones. We conclude that even though PRL can increase the amount of
      EGF mRNA in mammary epithelial cells, it also eliminates EGF-induced mitogenesis.

PMID- 8269987
TI  - A glycosylphosphatidylinositol-anchored cytokine can function as an artificial
      cellular adhesin.
AB  - A novel strategy for altering the adhesive properties of cells has been developed
      which is based upon the use of artificial adhesins. Specifically, a
      glycosylphosphatidylinositol (GPI)-modified variant of the cytokine macrophage
      colony stimulating factor (M-CSF), designated M-CSF.GPI, was expressed on the
      surface of human bone marrow stromal cells. A chimeric M-CSF:decay-accelerating
      factor expression construct was used for M-CSF.GPI expression. Cell:cell binding
      assays established that this artificially membrane-tethered cytokine functions as
      a potent cellular adhesin, allowing for enhanced binding to M-CSF receptor
      expressing cellular transfectants. Antibody blocking analyses confirmed the M
      CSF:M-CSF receptor dependence of the enhanced intercellular binding. This
      capacity to direct the cellular interactive repertoire of selected cells can in
      principle be applied to other cell types and other molecular pairs to be used in
      cell-based therapies.

PMID- 8269988
TI  - Regulation of asialoglycoprotein receptor expression in rat hepatocytes cultured
      under proliferative conditions.
AB  - The expression of many glycoproteins on the surface of hepatocytes has been
      related to the state of differentiation of the liver. In particular, the
      asialoglycoprotein receptor (ASGP-R) is modulated in many physiological and
      pathological conditions in which hepatocyte proliferative activity is modified.
      We studied ASGP-R expression in primary monolayer cultures of rat hepatocytes
      stimulated to proliferate by the addition of epidermal growth factor and insulin.
      In proliferating hepatocytes the receptor concentration on the cell surface was
      lowered, with no modifications in its distribution; similarly, both the binding
      activity and the amount of specific transcripts were decreased. The decreases
      were related to the peak of cellular growth, as judged by [3H]thymidine
      incorporation into DNA. The results suggest the presence of a cell cycle
      dependent ASGP-R expression also in in vitro systems; this control could be
      exerted by a decreased availability of receptor-specific mRNA molecules or on the
      stability of transcripts.

PMID- 8269989
TI  - Energy metabolism, replicative ability, intracellular calcium concentration, and
      ionic channels of horse articular chondrocytes.
AB  - Some aspects of the physiology of chondrocytes from horse articular cartilage
      were studied, since this animal model can be helpful in understanding arthritic
      processes. The replicative ability of articular chondrocytes, measured by the
      incorporation of [3H]thymidine, and their capacity of proteoglycan production,
      evaluated from the incorporation of [35S] sulfate, are very low. In addition,
      these cells do not differentiate in vitro as shown by the constant specific
      activity of alkaline phosphatase measured at different times in culture. Two
      types of potassium channels were identified by patch clamp experiments in the
      cell-attached configuration, one characterized by a conductance of 40 pS and the
      other of 100 pS. No active K+ channels were found at Vpip = 0. It was shown by
      Fura-2 experiments that the low replicative ability is paralleled by a modest
      variation of the intracellular calcium concentration after a mitogenic stimulus.
      31P NMR experiments, both on slices of whole articular cartilage and on isolated
      cells, demonstrate that chondrocytes derive their energy mainly from the
      glycolytic pathway.

PMID- 8269990
TI  - Autocrine regulation of the production of the gaseous messenger nitric oxide in a
      glioblastoma cell line.
AB  - We used a glioblastoma multiform (GBM) cell line to study the mechanism of
      cellular regulation of nitric oxide (NO) production. Our experiments indicate a
      confluent monolayer of GBM cells to release NO as measured through its oxidized
      NO2 form which gradually accumulates and reaches a peak by 7 to 10 days of
      culture. the addition of the L-arginine analogs L-NG-monomethyl-L-arginine and L
      N omega-nitro-L-arginine and dexamethasone to the GBM cultures caused a
      substantial inhibition of NO production. The addition of monoclonal antibodies
      against IL-1 and TNF alpha to the cultures resulted in an inhibition of NO
      production, whereas the addition of anti-TGF beta monoclonal antibodies resulted
      in an increase in NO production. These findings suggest the presence of an
      autocrine regulatory mechanism for NO production in some tumor cell lines.

PMID- 8269992
TI  - Different mode of cell death induced by calcium ionophore in human leukemia cell
      lines: possible role of constitutive endonuclease.
AB  - The mechanism of cell death induced by calcium ionophore, A23187, was
      investigated in six human leukemia cell lines. Following exposure to 1 microM
      A23187, the myelogenous cell lines (HL-60, U-937, KG-1) underwent apoptosis
      within 3 h as determined by their morphology and DNA fragmentation assay. In
      contrast, T-lymphoblastic leukemia cell lines (Molt-4, Molt-3, CEM) revealed
      necrotic cell death after 24 h of incubation. However, an initial rise of
      intracellular free calcium concentrations and growth inhibition after treatment
      with A23187 were similar in the two cell types. We further showed that an
      endonuclease capable of mediating internucleosomal DNA fragmentation was
      constitutively expressed in the cytosol but not in the nuclei of the myelogenous
      cell lines, although this endonuclease was not detected in either the nuclei or
      the cytosol of the T-lymphoblastic cell lines. The activation of the endonuclease
      in myelogenous cells is calcium-independent and has an optimal pH of 7.5-9. It is
      inhibited by 1 mM zinc ion or 300 microM aurintricarboxylic acid. We propose that
      this constitutive endonuclease may be related to the susceptibility of
      myelogenous leukemia cell lines to apoptotic cell death.

PMID- 8269991
TI  - Radixin is a component of hepatocyte microvilli in situ.

PMID- 8269993
TI  - Glucose-6-phosphate dehydrogenase gene expression in fetal hepatocyte primary
      cultures under nonproliferative and proliferative conditions.
AB  - The culture of fetal hepatocytes at high cell density for 64 h in medium
      supplemented with 5 mM glucose produced an induction of glucose-6-phosphate
      dehydrogenase (G6PD) mRNA in a time-dependent manner. Insulin and
      triiodothyronine (T3), separately, increase G6PD mRNA expression, producing an
      additive effect at 64 h when combined. Glucagon and, to a greater extent,
      dibutyryl-cAMP decreased the G6PD mRNA expression observed in the presence of 5
      mM glucose and T3. Dexamethasone repressed the G6PD mRNA expression induced by
      glucose and insulin and decreased this expression when induced by T3, regardless
      of the presence of insulin. At low cell density, EGF in the presence of
      dexamethasone induced in parallel DNA synthesis, G6PD mRNA content, and specific
      activity, while EGF failed to increase these parameters at high cell density. In
      addition, G6PD expression in proliferative fetal hepatocytes was unresponsive to
      lipogenic hormones.

PMID- 8269994
TI  - Regulation of the Max gene expression by different mitogenic pathways in dog
      primary thyrocytes.
AB  - The family of Myc proteins appears to function through heterodimerization with
      the bHLH-Zip protein Max. We have investigated the regulation of Max mRNA in
      primary cultured dog thyrocytes whose proliferation is stimulated by three
      distinct mitogenic pathways: (1) the thyrotropin (TSH) cascade mediated by cyclic
      AMP, (2) the protein kinase C pathway activated by diacylglycerol and phorbol
      esters such as 12-O-tetradecanoylphorbol 13-acetate (TPA), (3) a protein tyrosine
      kinase system activated by epidermal growth factor (EGF). Among these cascades
      only the first is compatible with differentiation. We have observed that the mRNA
      of Max is stable and regulated differentially by the three pathways in our
      system. TSH decreases the level of the messenger while EGF or TPA increases it
      with early delayed kinetics. The effect of cyclic AMP on the accumulation of Max
      is observed even in the presence of cycloheximide, while the EGF- or TPA-induced
      increase is cycloheximide sensitive, suggesting differences in regulation
      pathways. Max mRNA is regulated with the same intensity, but in a more delayed
      fashion than the messenger of c-myc. As Max protein mediates the transcriptional
      effects of c-Myc our results are compatible with a mediator role of Max in
      modulating the cell sensitivity to the proliferative signal c-Myc.

PMID- 8269995
TI  - Rat spermatid basic nuclear protein TP3 is the precursor of protamine 2.
AB  - A second protamine, P2, synthesized as a precursor in late spermatids, is present
      in the sperm of some mammals such as the mouse. On the other hand, the sperm of
      other mammals such as the rat do not contain the mature P2, although they have
      the gene for the protein. Here we report that the P2 precursor is synthesized in
      late spermatids of the rat and is identical to the protein named TP3. TP3 and
      four other proteins present in the sonication-resistant spermatids of rat (steps
      13-19) immunoreact with an antibody to human P2. By microsequencing the amino
      terminal ends of the immunoreacting bands, we show that TP3 is the primary
      translational product of the rat P2 gene and that at least two of the other bands
      are cleavage products of the precursor molecule. The cleavages occur between
      residues 10 and 11 and between 19 and 20, as is the case in the mouse. Basic
      nuclear protein extract of rat epididymal sperm also contains a protein that
      weakly immunoreacts with the antibody. This protein migrates along with the
      fastest immunoreacting band from late spermatids. By quantitating the amount of
      the precursor molecules, we conclude that appreciable levels of P2 precursors are
      present in rat late spermatids (about 9% of total protamines), but the processing
      appears to be impaired and most of the protein is lost from the chromatin by the
      spermatozoa stage.

PMID- 8269996
TI  - Chronic cyclic strain reduces adenylate cyclase activity and stimulatory G
      protein subunit levels in coronary smooth muscle cells.
AB  - Previous studies from this laboratory have demonstrated that acute cyclic strain
      causes a reduction in adenylate cyclase activity in cultured coronary vascular
      smooth muscle cells. The objective of this study was to test the hypothesis that
      chronic cyclic strain of coronary vascular smooth muscle cells also causes
      inhibition of adenylate cyclase activity and that this may be related to changes
      in G protein steady-state levels. Cultured smooth muscle cells obtained from
      porcine coronary artery were subjected to 24 h of cyclic strain of 20 kPa (24%
      maximum strain) at 60 cycles/min. Unstretched cells served as controls. Basal,
      Gpp(NH)p, and forskolin plus Mn(2+)-stimulated adenylate cyclase activities were
      inhibited significantly in stretched versus unstretched vascular smooth muscle
      cells. The reduction in adenylate cyclase activity observed after 24 h of cyclic
      strain was associated with a significant (P < 0.05 vs controls) reduction in
      steady-state levels of Gs alpha 45, whereas Gi alpha 1,2 and G beta levels
      remained unchanged. The data support the hypothesis that adenylate cyclase
      activity and G protein steady-state levels in coronary smooth muscle are
      sensitive to chronic cyclic strain. It suggests that the G protein adenylate
      cyclase effector pathway may play an important role in the subacute adaptation of
      the coronary circulation to changes in intravascular pressure.

PMID- 8269997
TI  - The expression of retinoid X receptor genes is regulated by all-trans- and 9-cis
      retinoic acid in F9 teratocarcinoma cells.
AB  - Two classes of nuclear receptors for retinoic acid (RA) have been identified-
      retinoic acid receptor (RAR) and retinoid x receptor (RXR). Previously, we
      demonstrated that all-trans-retinoic acid (t-RA) differentially self-regulated
      the expression of RAR alpha, -beta, and -gamma transcripts. In the present study,
      we examined the effect of t-RA and 9-cis-RA (c-RA) on the expression of RXR genes
      in F9 cells by Northern blot analyses. The results showed that t-RA increased the
      levels of both the 5.6-kb RXR alpha and 3.8-kb RXR gamma mRNAs, decreased the
      amounts of 2.3-kb RXR gamma mRNA, but had no significant effect on the levels of
      RXR beta mRNA. Addition of a cyclic AMP analog along with t-RA further induced
      the differentiation of F9 cells to become parietal endodermal cells, but did not
      change the regulatory patterns of RXR mRNAs. The RNA synthesis inhibitor,
      actinomycin D, blocked the induction of 5.6-kb RXR alpha and 3.8-kb RXR gamma
      mRNA by t-RA, suggesting that the regulations at least in part were at the
      transcriptional levels. The protein synthesis inhibitor, cycloheximide, induced
      the expression of 5.6-kb RXR alpha mRNA and further enhanced the inductive effect
      of t-RA. In contrast, cycloheximide prevented the t-RA-regulated expression of
      both 3.8- and 2.3-kb RXR gamma mRNA, suggesting that ongoing protein synthesis
      was required for the regulation of RXR gamma gene. In addition, c-RA exerted
      effects similar to those of t-RA on RXR gene expression. A concentration of 10(
      8) M was required for c-RA to regulate the expression of RXR genes, while 10(-9)
      M of t-RA was effective in regulating RXR genes. Addition of t-RA and c-RA
      simultaneously had neither synergistic nor additive effects in regulating RXR
      gene expression. These data suggest that RAR may play an important role in RA
      regulated RXR gene expression.

PMID- 8269998
TI  - Morphological characterization of scavenger receptor-mediated processing of
      modified lipoproteins by rat liver endothelial cells.
AB  - Scavenger receptor-mediated processing by rat liver endothelial cells in vivo is
      studied by using acetylated and oxidized low-density lipoproteins (LDL) as
      ligands. The cellular localization of acetylated LDL (Ac-LDL) is visualized by
      both immunohistochemistry and silver enhancement of ultrasmall gold particles
      conjugated to Ac-LDL. Scavenger receptor-mediated internalization by the
      endothelial cells only involves coated vesicle formation. Subsequently, three
      stages of processing are noticed, as represented by (i) large electron lucent
      vesicles, with ligand in close association to the membrane, (ii) relatively
      electron-lucent structures, with Ac-LDL dispersed over the vesicular lumen, while
      tubular membrane extensions did not contain ligand, and (iii) electron-dense
      vesicles in which the nondegradable gold particles of the conjugate accumulate,
      while the immunoreactivity for Ac-LDL is low. Addition of chloroquine, an
      inhibitor of lysosomal degradation, demonstrated that the relatively electron
      lucent and electron-dense structures represent subsequent stages of the lysosomal
      pathway of Ac-LDL, which was also verified by detection of the lysosomal enzyme
      cathepsin D. Evaluation of the processing of Ac-LDL and oxidized LDL, labeled
      with different fluorochromes, demonstrated that both ligands follow apparently
      the same intracellular pathway in the liver endothelial cells, since the
      fluorescent probes are predominantly localized in the same structures. It is
      concluded that the scavenger receptor-mediated processing of modified LDL by rat
      liver endothelial cells involves four morphologically distinguishable stages
      which represent a highly effective catabolic route, sustaining the important role
      of the liver endothelial cells in the protection against circulating atherogenic
      lipoproteins.

PMID- 8269999
TI  - Thapsigargin raises intracellular free calcium levels in human keratinocytes and
      inhibits the coordinated expression of differentiation markers.
AB  - Thapsigargin raises intracellular free calcium ([Ca2+]i) by potently inhibiting
      the endoplasmic reticulum Ca-ATPase, which sequesters calcium from the cytosol.
      In human keratinocytes a rise in [Ca2+]i has been associated with differentiation
      and therefore we investigated the action of thapsigargin on this process. At
      concentrations above 3 nM thapsigargin inhibited keratinocyte proliferation.
      Thapsigargin induced an immediate transient [Ca2+]i rise in calcium-free or 70
      microM calcium medium but a more prolonged rise in 2 mM calcium. For
      keratinocytes cultured in 70 microM calcium medium a late [Ca2+]i rise was also
      observed, after 6 h, similar to the effect of known differentiation stimuli.
      However, immunohistochemical techniques did not show any expression of the
      differentiation-specific protein involucrin, a component of the cornified
      envelope. When keratinocyte differentiation was induced by an increase in the
      extracellular calcium from 70 microM to 2 mM abundant involucrin and desmoplakin,
      a component of desmosomes, were synthesised. Both proteins gave staining patterns
      which suggested incorporation into structural proteins, but thapsigargin
      disrupted the calcium-induced pattern of involucrin and desmoplakin synthesis.
      Thapsigargin did not induce differentiation, possibly due to its inability to
      activate protein kinase C and raise inositol trisphosphate levels. We conclude
      that a rise in [Ca2+]i does not alone induce keratinocyte differentiation but may
      act with other intracellular signals to promote differentiation.

PMID- 8270000
TI  - Flow cytometric analysis of fluorescein-labeled nerve growth factor binding to
      A875 human melanoma cells.
AB  - The interaction of fluorescein-labeled nerve growth factor (NGF) with human
      melanoma cells (A875) has been studied in order to assess better methodology for
      rigorous NGF binding studies. The NGF was modified at a single carboxyl group
      with iodoacetamidofluorescein after reaction with carbodiimide and cystamine. The
      modified NGF showed full binding competence in competition with radiolabeled NGF
      and full biological activity in neurite outgrowth assays compared to native NGF.
      Binding to unfixed, viable cells was assayed using flow cytometry. This method
      offers the advantage that unbound ligand need not be separated from that which is
      cell-associated, thus avoiding perturbation of the binding equilibrium, and
      accurate, extensive statistical analysis is possible. Binding of fluorescein-NGF
      was mainly specific and saturable, with analysis by three methods of data
      treatment indicating a Kd of 0.8 to 3 nM at 4 degrees C. Time-based data
      acquisition allowed a continuous time course for binding to be generated. Binding
      reached a steady-state level within 5 min of exposure of the cells to the ligand.
      Kinetic and steady-state results obtained using fluorescein-NGF agree well with
      previous data produced by 125I-NGF binding studies. The main limitation of the
      flow cytometric method in the NGF system is the relative lack of sensitivity
      compared to the binding of radiolabeled NGF, partially due to unusual quenching
      of the fluorophore bound to NGF.

PMID- 8270001
TI  - The effects of fibroblast growth factors in long-term primary culture of
      dystrophic (mdx) mouse muscle myoblasts.
AB  - A reliable method for the primary culture of undifferentiated skeletal muscle
      cells is a prerequisite for the success of therapeutic strategies for Duchenne
      and Becker muscular dystrophies involving gene therapy. We have developed
      conditions for the long-term culture of both dystrophic and normal mouse muscle
      explants and have now successfully cultured both dystrophic and nondystrophic
      muscle satellite cells continuously for up to 18 months with minimal loss of stem
      cell phenotype and retention of the expression of muscle cell markers and the
      ability to fuse at high serum levels. Optimal culture conditions depend on both
      the age of the animal and the type of muscle explanted, but the majority of
      skeletal muscle explants produce large numbers of satellite cells within 4-10
      days of explanting when cultured in Dulbecco's modified Eagle's medium/Ham's F12
      medium supplemented with high levels of fetal calf serum (10-20%). A small
      proportion of explants will produce outgrowth when placed into serum-free medium
      and assay of the conditioned medium from these explants shows that they release
      large amounts of FGF-like activity(s) when compared to nonoutgrowing explants.
      This process can be augmented by the addition of acidic, but not basic, FGF.
      Cultures of both dystrophic and nondystrophic muscle grow predominantly as
      monomorphic rounded cells which stain positively with antibodies specific for
      skeletal fast muscle actin, myosin, and desmin. In the absence of substantial
      fibroblast cell contamination, these cells frequently form end-to-end connections
      and, under permissive conditions, they will fuse to form characteristic myotubes.
      A major difference observed between dystrophic and normal skeletal muscle
      explants was the reduction in fibroblast-like cell outgrowth of dystrophic
      explants.

PMID- 8270002
TI  - Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2
      expression and normal p53 suppresses cyclin A expression.
AB  - We show that expression of the p34cdc2 and cyclin A genes is induced by
      interleukin-2 in normal human T cells and present evidence to support the idea
      that these genes are deregulated in leukemic T cells. Our DNA sequencing data
      indicate that the promoter region of the p34cdc2 gene contains putative E2F-like
      binding sites which are recognized by Rb and binding sites for c-myb, Sp1, and
      ATF, and that the promoter region of the cyclin A gene contains binding sites for
      p53, Sp1, and ATF. In this study we focus on the effect of p53 and Rb on these
      cell cycle-regulatory genes. Cotransfection of Y79 human retinoblastoma cells
      with a p34cdc2 promoter-luciferase expression vector and a plasmid expressing the
      retinoblastoma gene (RB) indicated that RB suppresses p34cdc2 expression.
      Cotransfection of B104 rat neuroblastoma cells with a cyclin A promoter
      luciferase expression vector and a plasmid expressing the normal or mutant p53
      indicated that only the normal p53 suppresses cyclin A expression. In normal T
      cells, PHA stimulation reduces the amount of complexes in the p34cdc2 promoter
      between the E2F-like binding site and the RB gene product. These complexes were
      not detected in leukemic T cells. Our data support the idea that tumor
      suppressors modulate the expression of cell cycle-regulatory genes: RB regulates
      p34cdc2 expression and p53 regulates cyclin A expression.

PMID- 8270003
TI  - Virulence properties of Escherichia coli strains belonging to serogroups O26,
      O55, O111 and O128 isolated in the United Kingdom in 1991 from patients with
      diarrhoea.
AB  - Some strains of Escherichia coli belonging to serogroups O26, O55, O111 or O128
      produce Vero cytotoxin (VT). These serogroups are included in the range of
      enteropathogenic E. coli (EPEC) serogroups for which commercial antisera are
      available. In an attempt to obtain information on VT-producing strains other than
      those of serogroup O157, 122 strains belonging to these four serogroups and
      isolated in 1991 from patients with diarrhoea in the United Kingdom were tested
      for hybridization with VT probes. Only 18 of the 122 strains were VT-positive and
      these were O26 or O128. However 90 strains hybridized with the E. coli attaching
      and effacing (eae) probe (including 14 VT-positive strains) and 17 with the
      enteroaggregative E. coli (EAggEC) probe. For 78 eae-positive and 9 EAggEC
      positive strains, tissue culture tests correlated with the probe results as the
      strains gave, respectively, either localized adhesion and a positive fluorescent
      actin staining test or a characteristic aggregative attachment. A total of 111 of
      the 122 strains belonging to serogroups O26, O55, O111 or O128 possessed
      properties that may be associated with the ability to cause human diarrhoeal
      disease, and similar studies are needed on strains from the other classical EPEC
      serogroups.

PMID- 8270004
TI  - Cattle as a possible source of verocytotoxin-producing Escherichia coli O157
      infections in man.
AB  - In May-June 1992 cases of infection with verocytotoxin-producing (VT+)
      Escherichia coli O157 in South Yorkshire could have been associated with prior
      consumption of beef from a local abattoir. During investigation of the abattoir,
      bovine rectal swabs and samples of meat and surface swabs from beef carcasses
      were examined for E. coli O157, isolates of which were tested for toxigenicity,
      plasmid content and phage type. E. coli O157 was isolated from 84 (4%) of 2103
      bovine rectal swabs; of these 84, 78 (93%) were VT+, the most common phage types
      being 2 and 8, the types implicated in the cluster of human cases. Positive
      cattle were from diverse sources within England. E. coli O157 was isolated from 7
      (30%) of 23 carcasses of rectal swab-positive cattle and from 2 (8%) of 25
      carcasses of rectal swab-negative cattle. The study has shown that cattle may be
      a reservoir of VT+ E. coli O157, and that contamination of carcasses during
      slaughter and processing may be how beef and beef products become contaminated
      and thereby transmit the organism to man.

PMID- 8270005
TI  - A quantitative polymerase chain reaction method for the detection in avian faeces
      of salmonellas carrying the spvR gene.
AB  - A quick, semi-quantitative method of detecting Salmonella species which contain
      the virulence plasmid has been developed using the polymerase chain reaction
      (PCR). A pair of primers have been synthesized encompassing a 500 bp fragment of
      the spvR virulence gene. Competitor DNA consisting of the spvR gene with a 94 bp
      deletion situated between the primer recognition sequences, was cloned into a
      plasmid vector. Co-amplification of the 'unknown' target salmonella DNA with
      known quantities of competitor DNA in the same reaction tube gave PCR products of
      500 and 406 bp respectively. Visual assessment of the ratio of the two products
      on ethidium bromide stained agarose gels provided an estimate of the approximate
      number of salmonella cells present in avian faeces. The technique could be
      applied to detect quantifiably any non-host DNA in clinical samples if a suitable
      DNA sequence for primer construction is available.

PMID- 8270006
TI  - The problems of tracing a geographically widespread outbreak of salmonellosis
      from a commonly eaten food: Salmonella typhimurium DT193 in north west England
      and north Wales in 1991.
AB  - Geographically widespread outbreaks involving commonly isolated organisms and
      where the vehicles of infection are commonly eaten foodstuffs pose particular
      difficulties at a technical and organizational level. An outbreak of Salmonella
      typhimurium infection, affecting 39 people, spread over a wide area in North West
      England and North Wales in April and May 1991, was detected thanks to the
      practice of sending specimens to the national reference laboratory where phage
      typing and characterizing of antibiotic resistance patterns enabled the
      identification of a cluster of distinctive isolates (S. typhimurium DT193
      resistant to sulphonamides, trimethoprim and furazolidone). An investigation,
      involving twenty environmental health departments in addition to health
      authorities and the Public Health Laboratory Service, showed an association
      between the illness and eating loose sliced cooked ham (P = 0.004). Detailed
      tracing of the chain of supply of the ham showed this to be particularly cooked
      ham originating from a single small local producer (P = 0.00003). Further
      investigation of that producer revealed that a batch of ham distributed on one
      day in early April was undercooked due to a malfunction in cooking equipment.

PMID- 8270007
TI  - An outbreak of Salmonella mikawasima associated with doner kebabs.
AB  - During October 1992 an increase in the number of isolates of Salmonella
      mikawasima, a rare serotype, was noted including a cluster of nine cases in the
      South West Thames region. A case control study was conducted and univariate
      analysis showed a statistical association between illness and eating at take-away
      A for cases compared with household controls (P = 0.003) and with neighbourhood
      controls (P = 0.0245). Cases were also more likely to have eaten kebabs than were
      controls or average take-away A customers, implicating doner kebabs as the most
      likely vehicle of infection. Plasmid profile analysis of the nine cases' isolates
      showed them to be indistinguishable and to be characterized by a single plasmid
      of approximately 60 MDa. The original source of the Salmonella mikawasima
      contamination was not determined, but food preparation practices for kebabs at
      take-away A were insufficient to protect against illness if contaminated. This
      outbreak was only recognized because of the unusual serotype, but could be an
      indication of a more widespread problem with doner kebabs.

PMID- 8270008
TI  - The coccoid forms of Helicobacter pylori. Criteria for their viability.
AB  - The fact that Helicobacter pylori can revert to a coccoid form has stimulated
      speculation about its role in transmission and as a possible cause of reinfection
      in duodenal ulcer disease. Bismuth subcitrate (32 micrograms/ml), bismuth
      subsalicylate (64 micrograms/ml), amoxicillin (0.05 micrograms/ml) and
      erythromycin (4 micrograms/ml) inhibited the growth of H. pylori and stimulated
      the formation of basically respiring but non-culturable coccoid structures. The
      presence of polyphosphates as energy and phosphorus source permits a certain
      level of endogenous metabolism to preserve RNA and DNA, as well as structural
      components like cell wall, cell membrane and cytoplasma for at least 3 months.
      However, the applied standard laboratory methods were insufficient for regrowth
      of H. pylori out of the coccoid form.

PMID- 8270009
TI  - Genetic diversity and clonal relationships of Acinetobacter baumannii strains
      isolated in a neonatal ward: epidemiological investigations by allozyme, whole
      cell protein and antibiotic resistance analysis.
AB  - Sixty-five strains of Acinetobacter baumannii which had been isolated from
      patients and the indoor environment of a neonatal intensive care unit and, for
      comparative purposes, isolates from three other wards, were examined by means of
      electrotyping and analysis of whole-cell protein and antibiotic resistance
      patterns. Fourteen different electrotypes were determined. The predominant type,
      a multiply resistant acinetobacter clone, persisted in the neonatal ward over
      several months. The results underline the usefulness of electrophoretic
      subtyping, in particular by means of allozyme pattern and as a supplement to
      whole-cell protein pattern analysis, in epidemiological investigations into the
      routes of transmission of nosocomial A. baumannii infections.

PMID- 8270010
TI  - Intracellular growth of Legionella pneumophila serogroup 1 monoclonal antibody
      type 2 positive and negative bacteria.
AB  - Epidemiological evidence suggests that monoclonal antibody type 2 positive (MAB
      2+) Legionella pneumophila serogroup 1 (LP1) more often causes disease than do
      MAB 2- isolates, and there is evidence that MAB 2- LP1 grow less well in cells
      than do MAB 2+ bacteria. We tested the intracellular growth rates of ten randomly
      selected MAB 2- LP1 isolates, by using guinea-pig alveolar macrophages, and human
      monocyte-derived macrophages. Save a low virulence control, all ten MAB 2-
      isolates grew as well in cells as a virulent MAB 2+ isolate. Heterogeneity of MAB
      2- LP1 growth in cells exists, making poor intracellular growth an unlikely
      explanation for why MAB 2+ LP1 appear to cause disease more often.

PMID- 8270011
TI  - Malaria transmission rates estimated from serological data.
AB  - A mathematical model was used to estimate malaria transmission rates based on
      serological data. The model is minimally stochastic and assumes an age-dependent
      force of infection for malaria. The transmission rates estimated were applied to
      a simple compartmental model in order to mimic the malaria transmission. The
      model has shown a good retrieving capacity for serological and parasite
      prevalence data.

PMID- 8270012
TI  - Malaria prevalence amongst Brazilian Indians assessed by a new mathematical
      model.
AB  - An alternative way to estimate the endemic level of malaria amongst Brazilian
      indians is proposed. This is achieved by estimating the age-related 'force of
      infection' of malaria (the effective inoculation rate), applying a mathematical
      model, described elsewhere, to serological data. In addition we present a way to
      estimate the Basic Reproductive Rate of malaria in the same area. The results
      have shown a good degree of accuracy in describing the endemic pattern of malaria
      in the area, and also indicate some relevant aspects of its age distribution
      related to the design of control strategies.

PMID- 8270013
TI  - Antigenic and genetic analyses of influenza type B viruses isolated in Russia,
      1987-91.
AB  - Four influenza type B viruses isolated in Russia during periods of relatively low
      (1987-8) or high (1990-1) influenza B activity were characterized antigenically
      using a microneutralization assay. These isolates were antigenically similar to
      contemporary reference strains from either of two separate lineages represented
      by B/Victoria/2/87 and B/Yamagata/16/88. The evolutionary relationships of the
      variable portion of the haemagglutinin (HA1) genes of these viruses were
      determined by comparison with influenza B HA1 sequences previously obtained. The
      Isolate B/USSR/2/87, collected during the 1987-8 influenza season, was found to
      be closely related to viruses on the B/Victoria/2/87 lineage that circulated
      during the 1988-9 influenza season in the United States. Sequence analysis of the
      isolates from the 1990-1 influenza season demonstrated cocirculation of viruses
      from both the B/Victoria/2/87 and B/Yamagata/16/88 lineages in Russia, confirming
      the antigenic analysis.

PMID- 8270014
TI  - Enzyme-linked immunosorbent assays for the detection of antibody to Crimean-Congo
      haemorrhagic fever virus in the sera of livestock and wild vertebrates.
AB  - IgM antibody response to Crimean-Congo haemorrhagic fever (CCHF) virus was
      monitored in experimentally infected sheep and cattle by an IgM capture enzyme
      linked immunoassay (ELISA). Specific binding of antigen was detected by a rabbit
      anti-CCHF horseradish peroxidase conjugate or a sandwich technique with
      hyperimmune mouse anti-CCHF ascitic fluid and commercially available anti-mouse
      immunoglobulin peroxidase conjugate. The persistence of IgM antibody activity was
      found to be of shorter duration than in humans, and this may be a function of the
      relative lack of susceptibility of these animals to infection with CCHF virus.
      IgG antibody responses in the sheep could be monitored by sandwich ELISA using
      commercially available anti-sheep immunoglobulin peroxidase conjugates. Total
      antibody activity in the sera of experimentally infected sheep, cattle and small
      mammals could be monitored in a competitive ELISA (CELISA) using rabbit anti-CCHF
      peroxidase conjugate. The CELISA was applied to the sera of 960 wild vertebrates
      from a nature reserve in South Africa, and the prevalence of antibody was found
      to be greatest in large mammals such as rhinoceros, giraffe and buffalo, which
      are known to be the preferred hosts of the adult tick (Hyalomma) vectors of the
      virus.

PMID- 8270015
TI  - The role of wild animals, other than buffalo, in the current epidemiology of foot
      and-mouth disease in Zimbabwe.
AB  - Between 1989 and 1992, 7970 wild ungulates, comprising 14 different species, were
      tested for antibodies to types SAT 1, SAT 2 and SAT 3 foot-and-mouth disease
      (FMD) virus. Of these 1.2% were found to be positive and these included impala
      (Aepyceros melampus), eland (Taurotragus oryx), waterbuck (Kobus ellipsiprymnus)
      and sable (Hippotragus niger). All the positive animals were either from the
      wildlife areas where buffalo (Syncerus caffer) occur or from ranches where
      clinical FMD had occurred in cattle. The role of these animal species in the
      current epidemiology of FMD in Zimbabwe is discussed.

PMID- 8270016
TI  - Origin of phasic synaptic inhibition in myotomal motoneurons during fictive
      locomotion in the lamprey.
AB  - The periodic membrane potential fluctuations in motoneurons during fictive
      locomotion in the lamprey, a primitive vertebrate, involve phasic synaptic
      excitation and inhibition. This paper investigates the origin of the phasic
      synaptic input to lamprey myotomal motoneurons in the in vitro spinal cord
      preparation with regard to the relative contribution of descending propriospinal
      input from interneurons in the local segment. The synaptic drive to myotomal
      motoneurons in the most rostral and the most caudal part of the spinal cord
      preparation are compared before and after selective spinal cord lesions. Current
      clamp recordings of the same cell before and after lesion showed that neither the
      excitatory phase nor the inhibitory phase was abolished after interruption of the
      descending or the ascending ipsilateral input, or after interrupting crossing
      segmental input by a local longitudinal midline incision. None of these sources
      thus appears to be alone responsible for the phasic synaptic drive. To
      quantitatively evaluate these effects, and in particular the contribution from
      the descending propriospinal fibres to the inhibitory phase, voltage clamp
      recordings were made in combination with a spinal cord hemisection just rostral
      to the motoneuron. The input from propriospinal interneurons in approximately 15
      rostral segments may be responsible for as much as 70% of the phase of inhibitory
      current during the locomotor cycle. In accordance with these findings, a similar
      voltage clamp analysis of rostrally and caudally located motoneurons showed that
      the average peak-to-peak amplitude of the current fluctuations in rostral cells
      was approximately 50% of that in caudal cells.

PMID- 8270017
TI  - Functional reorganization of the noradrenergic system after partial fornix
      section: a behavioral and autoradiographic study.
AB  - Previous experiments revealed that the cholinergic deficit in rats with a partial
      fornix section was accompanied by an increase in turnover of noradrenaline (NE)
      in the hippocampus. This noradrenergic hyperactivity contributed to the cognitive
      deficit in lesioned rats, probably by interaction with the cholinergic system.
      The present experiment examines the reorganization of the noradrenergic system
      after the damage induced by partial fornix section and attempts to determine if
      the increase in NE turnover is of locus coeruleus (LC) origin, or if it is a
      result of local regulation at the noradrenergic terminals. Rats were submitted to
      knife-cut section of the fornix, resulting in a decrease in choline
      acetyltransferase activity in the hippocampus, correlated with a significant
      behavioral deficit in a spatial memory task. Lesioned rats learned a nonspatial
      memory task normally. Sections of brains of these rats were submitted to
      quantitative autoradiography. [125I]Iodopindolol binding was assessed in the
      dorsal and ventral hippocampus to determine availability of beta receptors. This
      was found to be significantly lower in lesioned rats. [125I]Iodoclonidine was
      used to determine alpha 2 receptors binding in dorsal and ventral hippocampus and
      in LC. There was no difference in alpha 2 receptors in LC, a significant decrease
      in dorsal regions of the hippocampus, and a significant increase in ventral
      regions. Muscarinic M1 receptors in the hippocampus showed no changes after the
      lesion.

PMID- 8270018
TI  - Orientational influences of layer V of visual area 18 upon cells in layer V of
      area 17 in the cat cortex.
AB  - We examined the orientation tuning curves of 86 cells located in layer V of area
      17, before, during, and after focal blockade of a small (300-microns diameter)
      region of near-retinotopic register in layer V of area 18 of quantitatively
      established orientation preference. Such focal blockade revealed three distinct
      populations of area 17 layer V cells-cells with decreased responses to stimuli of
      some orientations (21%), cells with increased responses to stimuli of some
      orientations (43%), and cells unaffected by the focal blockade (36%). These
      effects were clearcut, reproducible, and generally directly related to the known
      receptive field properties of the cell recorded in area 18 at the center of the
      zone of blockade. These effects were also analyzed in terms of alterations in
      orientation bandwidth in the cells in area 17 as a result of the blockade
      bandwidth increases (22%) and decreases (24%) were found; however, these changes
      were essentially unrelated to the measured receptive field properties. Inhibitory
      and excitatory effects were most pronounced when the regions in areas 17 and 18
      were of like ocular dominance and were of similar orientation preference.
      Inhibitory effects (suggesting a normally excitatory input) were most dependent
      upon the similarity of receptive fields; excitatory effects (suggesting a
      normally inhibitory input) were less heavily dependent.

PMID- 8270019
TI  - Parietal neurons encoding spatial locations in craniotopic coordinates.
AB  - The receptive fields of visual neurons are known to be retinotopically arranged,
      and in awake animals they "move" with gaze, maintaining the same retinotopic
      location regardless of eye position. Here, we report the existence in the monkey
      parietal cortex of cells (called "real-position" cells) whose receptive field
      does not systematically move with gaze. These cells respond to the visual
      stimulation of the same spatial location regardless of eye position and therefore
      directly encode visual space in craniotopic instead of retinotopic coordinates.

PMID- 8270020
TI  - Response properties of neurons in area 17 projecting to the striate-recipient
      zone of the cat's lateralis posterior-pulvinar complex: comparison with cortico
      tectal cells.
AB  - The main input of the lateral part of the cat's lateralis posterior-pulvinar
      complex (LP-P) comes from the primary visual cortex. We investigated the response
      properties of cells in area 17 projecting to the striate-recipient zone (LP1) of
      the cat's LP-P complex. The cells' receptive fields were stimulated with drifting
      sine-wave gratings. Cells whose fibres terminate in the superior colliculus were
      also recorded, to determine how their properties compare with those of cortico
      LP1 cells and to investigate the possibility that LP1 is innervated by
      collaterals of cortico-tectal units. A total of 26 cells in the striate cortex
      were identified by antidromic activation from the LP1 (mean latency 2.2 ms) and
      22 from the colliculus (mean latency 2.5 ms). Only six cortical cells could be
      activated from the LP1 and the colliculus. All cortico-LP1 cells except for two
      responded to drifting sinusoidal gratings with unmodulated discharges (AC/DC
      ratios < 1). On the basis of their modulation index, these units were classified
      as complex cells. All cortico-LP1 cells were selective for the orientation of
      gratings (mean bandwidth of 28 degrees). There was a tendency for cortico-LP1
      cells to prefer vertical and horizontal orientations. More than half of these
      cells (57%) were direction selective. Strong orientation anisotropies were also
      found in the receptive fields of cortico-tectal cells, since almost all units
      responded preferentially to horizontally oriented gratings.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8270021
TI  - Responses of feline caudal hypothalamic cardiorespiratory neurons to hypoxia and
      hypercapnia.
AB  - Several studies have suggested that the caudal hypothalamus modulates responses
      to hypercapnia and hypoxia. In addition, this area of the hypothalamus contains
      neurons that have a sympathoexcitatory discharge. The purpose of the present
      study was to determine whether the basal discharge of caudal hypothalamic neurons
      that are stimulated by hypercapnia or hypoxia is related to cardiovascular
      (sympathetic discharge and/or the cardiac cycle) and/or respiratory activity
      (phrenic nerve discharge). Hypothalamic single unit activity, phrenic nerve
      activity, and cervical sympathetic nerve activity were recorded in anesthetized
      cats. Computer averaging techniques were used to compare temporally the discharge
      of hypothalamic neurons with cardiovascular and/or respiratory activity.
      Cardiorespiratory and hypothalamic neuronal responses to ventilation with hypoxic
      (10% O2/90% N2) and hypercapnic (5% CO2/95% O2) gases were determined in intact
      and in peripherally-chemodenervated, barodenervated cats. Thirty-two percent of
      hypothalamic neurons were stimulated by a hypercapnic stimulus in intact cats; of
      those that were stimulated by hypercapnia, all had a basal discharge related to
      cardiovascular and/or respiratory activity. Hypoxia significantly increased the
      discharge rate of 21% of hypothalamic units in intact animals; 90% of those had a
      cardiovascular and/or respiratory-related rhythm. Only 13% of the neurons were
      stimulated by both hypoxia and hypercapnia. Similar results were found in
      barodenervated, peripherally chemodenervated cats. Neurons excited by these
      stimuli in both the intact and denervated cats were found to be concentrated in
      the posterior hypothalamic area. The results of this study suggest that a group
      of caudal hypothalamic neurons contribute to the cardiorespiratory responses to
      hypoxia and hypercapnia, but via separate subpopulations of neurons. In addition,
      input from peripheral baroreceptor and chemoreceptor afferents is not required
      for this modulation.

PMID- 8270022
TI  - Spike trains and signaling modes of neurons in the ferret lateral geniculate
      nucleus.
AB  - Intracellular recordings were used to examine the action potential firing modes
      of cells in the ferret lateral geniculate nucleus (LGN) in vitro. We compared the
      effects of altered membrane voltage on patterns of action potential trains evoked
      by direct current injection and by retinal afferent (synaptic) stimulation. The
      results confirm that LGN cells in the ferret can fire action potentials in the
      "burst" and "tonic" modes that have been described previously for other species.
      At depolarized membrane potentials, LGN neurons respond to sustained
      depolarization with short-latency trains of action potentials whose frequency is
      directly proportional to the amount of current injected. At hyperpolarized
      membrane potentials, LGN cells enter burst mode, in which depolarizing inputs are
      differentiated into brief high-frequency discharges whose latency varies with
      membrane potential. We also observed a "mixed" mode, in which LGN cell responses
      to synaptic or injected currents within a narrow range of membrane potentials
      reflect aspects of both burst and tonic firing simultaneously. Thus a striking
      consequence of the interplay among voltage-dependent membrane conductances in
      thalamic cells is wide variability in length, duration, and latency of spike
      discharges elicited by identical stimuli. These results also suggest that the
      concept that LGN cells display only two active response modes must be expanded to
      include varying amounts of delay and the possibility of mixed discharges.

PMID- 8270023
TI  - Convergence of somatic and visual afferent impulses in the Wulst of pigeon.
AB  - In 79 pigeons, unit discharges of Wulst neurons responding to bilateral
      stimulation of N. radialis and N. sciaticus and to bilateral light flashes were
      recorded. Of 178 such neurons, 55 showed multisensory convergence of various
      types: 40 of these were somatic convergent neurons, characterized as 3 types;
      three were binocular convergent cells; and twelve were bimodal (visual
      somatosensory) convergent neurons. Of these neurons, the convergent action was
      either inhibitory or excitatory. These results suggest that the Wulst may
      function as an important centre for integrating visual and somatic sensory
      information.

PMID- 8270024
TI  - Phases in the development of a penicillin epileptiform focus in rat neocortex.
AB  - Somatosensory evoked potentials and potentials evoked by direct cortical
      stimulation were recorded from layer IV of the somatosensory area of the cerebral
      cortex in urethane anaesthetised rats. Penicillin was expelled
      electrophoretically from the tip of a drug-filled micropipette at constant rates
      into layer IV. Small fluxes of penicillin (with electrophoretic currents of -50
      to -90 nA) resulted in the appearance, after a delay of 1-2 min, of an
      enhancement of amplitude in the voltage of both types of evoked potential,
      unaccompanied by any prolongation of the waveform or spontaneous focal
      epileptiform discharges. The amplitude of the enhanced evoked potential exhibited
      a strength-response curve which was a scaled-up version of the curve before
      penicillin, the scaling factor reflecting the enhancement of amplitude. As the
      interval between a pair of stimuli was increased, the magnitude of the response
      to the second stimulus recovered, following a time course similar to that before
      penicillin. With larger fluxes of penicillin (with electrophoretic currents of 
      250 to -1000 nA) the amplitude of evoked potentials rose more rapidly and to a
      higher level; as the concentration of penicillin rose, this enhancement of
      amplitude led into a second phase, in which there was additionally an increase in
      the duration of the evoked potentials and the appearance of spontaneous
      epileptiform discharges. The evoked potentials in this situation showed
      physiological properties different from those before penicillin application. The
      strength-response curve exhibited a discontinuity, indicating the evoked
      potential to be the sum of a physiological response and an epileptiform
      discharge, the former being graded with stimulus strength and the latter being
      all or none.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270025
TI  - Otolith responses in man during parabolic flight.
AB  - The influence of the varying gravito-inertial (Gz) force during parabolic flight
      on human otolith function was investigated experimentally. It was hypothesised
      that a varying Gz force profile initiates an otolith-ocular response that
      manifests itself in modulation of optokinetic nystagmus slow-phase eye velocity
      (OKN-SPV). Six subjects were seated in the ESA-Caravelle, facing perpendicular to
      the aircraft's longitudinal axis. The Gz profile was subsequently 1.8 Gz pull-up,
      0 Gz microgravity, and 1.8 Gz recovery, each phase lasting about 20 s. Vertical
      eye movements were recorded with electro-nystagmography throughout the parabolic
      manoeuvre. Conditions were: (1) visual fixation, (2) darkness and (3) optokinetic
      stimulation of 50 deg/s in an upward or downward direction, projected on a
      cylindrical screen at 0.6 m viewing distance. No consistent nystagmus or gaze
      shift was measured in darkness. With optokinetic stimulation, however, ANOVA
      revealed downward enhancement of OKNSPV by 5 degrees/s in 1.8 Gz hypergravity, as
      compared with the 0 Gz condition and the 1 Gz condition. It is concluded that an
      otolith-ocular pathway modulates optokinetic eye movements in parabolic flight.

PMID- 8270026
TI  - Vestibular perception of passive whole-body rotation about horizontal and
      vertical axes in humans: goal-directed vestibulo-ocular reflex and vestibular
      memory-contingent saccades.
AB  - This study was aimed at complementing the existing knowledge about vestibular
      perception of self-motion in humans. Both goal-directed vestibulo-ocular reflex
      and vestibular memory-contingent saccade (VMCS) tasks were used, respectively as
      concurrent and retrospective magnitude estimators for passive whole-body
      rotation. Rotations were applied about the earth-vertical and earth-horizontal
      axes to study the effect of the otolith signal in self-rotation evaluation, and
      both in yaw and pitch to examine the horizontal and vertical semi-circular
      canals. Two different magnitudes of constant angular acceleration (50 degrees/s2
      and 100 degrees/s2) were used. The main findings were (1) strong correlation
      between both oculomotor responses of both tasks, (2) greater accuracy with
      rotations about the earth-vertical than the earth: -horizontal axis, (3) greater
      accuracy for yaw than for pitch rotations, (4) greater accuracy for high
      acceleration than for low, and (5) no effect of the delay (2 s or 12 s) in the
      VMCS task. Adequacy of both tasks as subjective magnitude estimators of
      vestibular perception of self-motion is discussed.

PMID- 8270027
TI  - Independent control of reflex and volitional EMG modulation during sinusoidal
      pursuit tracking in humans.
AB  - It is well known that during volitional sinusoidal tracking the long-latency
      reflex modulates in parallel with the volitional EMG activity. In this study, a
      series of experiments are reported demonstrating several conditions in which an
      uncoupling of reflex from volitional activity occurs. The paradigm consists of a
      visually guided task in which the subject tracked a sinusoid with the wrist. The
      movement was perturbed by constant torque or controlled velocity perturbations at
      45 degrees intervals of the tracking phase. Volitional and reflex-evoked EMG and
      wrist displacement as functions of the tracking phase were recorded. The
      relationship of both short-latency (30-60 ms) and longer-latency (60-100 ms)
      reflex components to the volitional EMG was evaluated. In reflex tracking, the
      peak reflex amplitude occurs at phases of tracking which correspond to a maximum
      of wrist joint angular velocity in the direction of homonymous muscle shortening
      and a minimum of wrist compliance. Uncoupling of the reflex and volitional EMG
      was observed in three situations. First, during passive movement of the wrist
      through the sinusoidal tracking cycle perturbation-evoked long-latency stretch
      reflex peak is modulated as for normal, volitional tracking. However, with
      passive joint movement the volitional EMG modulation is undetectable. Second, a
      subset of subjects demonstrate a normally modulated and positioned long-latency
      reflex with a single peak. However, these subjects have distinct bimodal peaks of
      volitional EMG. Third, the imposition of an anti-elastic load (positive position
      feedback) shifts the volitional EMG envelope by as much as 180 degrees along the
      tracking phase when compared with conventional elastic loading. Yet the long
      latency reflex peak remains at its usual phase in the tracking cycle,
      corresponding to the maximal velocity in the direction of muscle shortening.
      Furthermore, comparison of the results from elastic and anti-elastic loads
      reveals a dissociation of short- and long-latency reflex activity, with the short
      latency reflex shifting with the volitional EMG envelope. Comparable results were
      also obtained for controlled velocity perturbations used to control for changes
      in joint compliance. The uncoupling of the reflex and volitional EMG activity in
      the present series of experiments points to a flexible relationship between
      reflex and volitional control systems, altered by peripheral input and external
      load.

PMID- 8270028
TI  - Effects of local anaesthetics on retinal spreading depression.
AB  - This study examines the effect of two local anaesthetics, benzocaine and
      lidocaine, on propagation, amplitude and duration of the slow potential change of
      spreading depression. The experiments were performed in isolated chick retina
      superfused with Ringer's solution. We observed, for both drugs, a dose-related
      decrease in all parameters analysed. The maximal effect on propagation was
      blockade of the reaction.

PMID- 8270029
TI  - Biology of halophilic bacteria, Part II. Membrane lipids of extreme halophiles:
      biosynthesis, function and evolutionary significance.
AB  - Archaebacteria (archaea) are comprised of three groups of prokaryotes: extreme
      halophiles, methanogens and thermoacidophiles (extreme thermophiles). Their
      membrane phospholipids and glycolipids are derived entirely from a saturated,
      isopranoid glycerol diether, sn-2,3-diphytanylglycerol ('archaeol') and/or its
      dimer, dibiphytanyldiglyceroltetraether ('caldarchaeol'). In extreme halophiles,
      the major phospholipid is the archaeol analogue of
      phosphatidylglycerolmethylphosphate (PGP-Me); the glycolipids are sulfated and/or
      unsulfated glycosyl archaeols with diverse carbohydrate structure characteristic
      of taxons on the generic level. Biosynthesis of these archaeol-derived polar
      lipids occurs in a multienzyme, membrane-bound system that is absolutely
      dependent on high salt concentration (4 M). The highly complex biosynthetic
      pathways involve intermediates containing glycerol ether-linked C20-isoprenyl
      groups which are reduced to phytanyl groups to give the final saturated polar
      lipids. In methanogens, polar lipids are derived both from archaeol and
      caldarchaeol, and thermoacidophiles contain essentially only caldarchaeol-derived
      polar lipids. The function of these membrane polar lipids in maintaining the
      stability, fluidity and ionic properties of the cell membrane of extreme
      halophiles, as well as the evolutionary implications of the archaeol and
      caldarchaeol-derived structures will be discussed.

PMID- 8270030
TI  - Photoreceptor damage following exposure to excess riboflavin.
AB  - Flavins generate oxidants during metabolism and when exposed to light. Here we
      report that the photoreceptor layer of retinas from black-eyed rats is reduced in
      size by a dietary regime containing excess riboflavin. The effect of excess
      riboflavin was dose-dependent and was manifested by a decrease in photoreceptor
      length. This decrease was due in part to a reduction in the thickness of the
      outer nuclear layer, a structure formed from stacked photoreceptor nuclei. These
      changes were accompanied by an increase in photoreceptor outer segment
      autofluorescence following illumination at 328 nm, a wavelength that corresponds
      to the excitation maxima of oxidized lipopigments of the retinal pigment
      epithelium.

PMID- 8270031
TI  - Lactate dehydrogenase and glutamate dehydrogenase activities in the
      circumventricular organs of rat brain following neonatal monosodium glutamate.
AB  - Glutamate (glu) an excitatory neurotransmitter amino acid, is present in high
      concentrations in the mammalian central nervous system and is the most abundant
      amino acid in our daily diet. In the present study the activities of lactate
      dehydrogenase (LDH) and glutamate dehydrogenase (GDH) were evaluated in the
      circumventricular organs (CVO) of the brain in 25-day-old rats following MSG
      administration at a dose of 4 mg/g b.wt during the first ten days of life. The
      results show the LDH activity increased to 265% of that in the control (p <
      0.001), whereas GDH activity was significantly decreased (p < 0.05). The great
      elevation in LDH, a cytoplasmic marker enzyme, is apparently due to cytoskeletal
      changes brought about as a consequence of glu toxicity, whereas lowered GDH
      activity indicates altered glu homostasis in the blood-brain-barrier deficient
      areas following neonatal exposure to glu.

PMID- 8270032
TI  - Anti-lipopolysaccharide activity of histatins, peptides from human saliva.
AB  - Histatins are histidine-rich polypeptides secreted in human saliva. They were
      found to inhibit lipopolysaccharide (LPS)-mediated gelation of Limulus amoebocyte
      lysate, and to reverse the anti-complement action of LPS or lipid A. Histatins
      also gave precipitate bands in agarose gels with various LPS. The results
      indicate that histatins neutralized the activity of LPS by binding to the lipid A
      moiety of LPS.

PMID- 8270033
TI  - A lectin from the liverwort Marchantia polymorpha L.
AB  - Bryophytes have been screened for lectins. From the liverwort Marchantia
      polymorpha (Marchiantiales) a lectin could be purified to homogeneity using a
      combination of ultrafiltration, size exclusion chromatography and ion exchange
      chromatography. SDS polyacrylamide gel electrophoresis, size exclusion
      chromatography and electrospray mass spectroscopy showed that the lectin is a
      monomeric protein with a M(r) of 16,134.64 +/- 2.93. Marchantia polymorpha lectin
      agglutinates erythrocytes of different mammalia and exhibits carbohydrate
      specificity against complex carbohydrate structures. This is the first report of
      a lectin isolated from liverworts.

PMID- 8270034
TI  - Surgical oncology.

PMID- 8270035
TI  - Anaplastic carcinoma of the thyroid.
AB  - A review of 48 cases of anaplastic cell carcinoma of the thyroid gland treated in
      the Department of E.N.T. of Beilinson Medical Center revealed more than 90% of
      the patients to be over 50 years of age. Twenty-five percent of the patients
      showed, histologically, areas of transition from differentiated carcinoma (either
      papillary or follicular) into anaplastic carcinoma. The patients were treated by
      surgery and/or irradiation and/or chemotherapy. Twenty-seven patients underwent
      subtotal or total thyroidectomy and 21 patients underwent biopsy or partial
      thyroidectomy. The survival rate was very poor, two-year survival rate was 28%.
      Twenty-eight of the patients (58%) died within one year of diagnosis.

PMID- 8270036
TI  - Prognostic value of the tall cell variety of papillary cancer of the thyroid.
AB  - We analyse a new variety of papillary carcinoma of the thyroid, known as the tall
      cell variant. The lesion is characterized by a papillary cancer (PCT) in which
      more than 30% of the tumour is made up of a population of tall columnar cells
      over twice as tall as their width. Of a population of 158 differentiated thyroid
      carcinomas we found five cases of this rare variant. We studied their clinico
      pathological features, the importance of an early diagnosis and their prognostic
      implications. The data were compared with those of Well-Differentiated or
      Classical PCT (WDPC), the most important features of which were: (a) later age of
      appearance; (b) greater predilection for males; (c) greater frequency of
      extrathyroid tumor extensions; (d) greater frequency of recurrences; and (e) a
      shorter survival or disease-free interval. The prognostic importance involved in
      recognizing this variant is based on the need to give patients a more aggressive
      treatment and more exhaustive follow-up.

PMID- 8270037
TI  - Expression of tumour-associated antigens in breast cancer primary tissue compared
      with serum levels.
AB  - The level of expression of six breast cancer-associated antigens or markers (CEA,
      NCRC-11, HMFG1, HMFG2, D8 and DF3) in primary tumour tissue and patients' serum
      has been compared. Two-hundred-and-forty-five consecutive patients with newly
      diagnosed breast cancer had tumour biopsy and serum samples taken prior to any
      anti-cancer therapy (Stage I and II disease n = 100, Stage III disease n = 60,
      Stage IV disease n = 85). No correlations were found between the level of tumour
      tissue staining and serum levels of the same antigens. Those samples from
      patients with Stage IV disease were also analysed separately but again no
      correlations were observed. Therefore the staining pattern of the primary tumour
      for these antigens is not a predictor of which tumour marker will be elevated in
      the serum.

PMID- 8270038
TI  - Tumorectomy plus tamoxifen for the treatment of breast cancer in the elderly.
AB  - Between 1987 and 1991 a total of 37 breast cancer patients with a mean age of
      78.8 (68-89) years underwent local tumor excision and were continuously given 20
      30 mg tamoxifen. Thirteen patients presented with clinical stage I, 21 with stage
      II, two patients with stage III and one woman with stage IV. Surgical
      complications were minimal and hospital stay 3.5 days. Four patients were lost to
      follow-up. After a mean observation time of 44.5 months, three of the remaining
      patients developed local recurrence, which was excised, and 12 patients (32.4%)
      died. Death, however, was never related to breast cancer. One further patient
      developed visceral metastases after 46 months of treatment, which responded well
      to an increase in tamoxifen. The patient with osseous metastases at the time of
      diagnosis is still alive with stable disease after 75 months. Growing axillary
      lymph nodes were dissected 16 and 22 months after primary surgery in two
      patients. It is concluded from this series that limited surgery with hormonal
      therapy is an effective treatment of breast cancer in elderly patients.

PMID- 8270039
TI  - Gastric carcinoma: study of the most eminent prognostic factors.
AB  - In order to analyse some prognostic factors in relation to gastric cancer, 218
      patients were included in a prospective protocol at 'Hospital General de Elche'
      (Spain) with a follow-up of 100%. Survival curves were calculated using Kaplan
      Meier analysis and compared using the log-rank test. The number of patients who
      underwent resection was 122 (63.5%). In 70 cases (36.5%) the resection was not
      possible. The postoperative mortality was 4.9%. In the survival of patients with
      gastric cancer we find the following prognostic factors are significant: age,
      tumour site, macroscopic type, depth of gastric wall affection, presence of lymph
      nodes, staging, resectability and surgical intention (curative vs palliative).

PMID- 8270040
TI  - Is dietary restriction always necessary in Haemoccult screening for colorectal
      neoplasia?
AB  - Certain dietary constituents may cause guaiac-based faecal occult blood tests to
      be positive in the absence of blood loss. In a randomized controlled study of
      Haemoccult screening for the early detection of colorectal cancer, a policy of
      retesting with appropriate dietary restriction is used to minimize false-positive
      results. Delay associated with the retesting protocol may cause considerable
      anxiety. The aim of the study was to determine the likelihood of an initial
      positive result remaining positive after retesting. One-hundred-and-thirteen of
      137 (35.6%) subjects whose initial test was < 5 squares positive remained
      positive in contrast to 52/59 (88.1%) with > or = 5 squares positive, a
      significantly higher proportion (P < 0.001). This suggests that if five or more
      test squares are positive, then dietary interference is unlikely to be
      responsible. We conclude that, if dietary restriction retesting is practiced,
      individuals with strongly positive tests may be offered investigation without
      retesting, thus reducing their delay to further investigation.

PMID- 8270041
TI  - The interscapulothoracic amputation in the treatment of malignant diseases of the
      upper extremity with a review of the literature.
AB  - The majority of patients with soft tissue sarcoma (STS) or bone sarcomas (BS) of
      the upper limb can be treated today with limb saving procedures using combined
      modality therapies. However, for a small group of patients the
      interscapulothoracic (IST) amputation is the only final surgical treatment with
      either a curative or a palliative intent. Since 1972, 12 patients seven males and
      five females, median age 36 years (range 13-82) underwent an interscapulothoracic
      amputation; five for bone sarcomas, five for soft tissue sarcoma and two for
      locoregional metastases. There was no post-operative mortality or morbidity.
      During a median follow-up of 8 years (range 0.25-15), there was no local
      recurrence. The five-year survival rate for the soft tissue sarcomas was 80% and
      for the bone sarcomas 30%. The interscapulothoracic amputation is one of the
      major ablative surgical procedures which should be performed with curative
      intent, very rarely with a low palliative intent. The prognosis of an
      interscapulothoracic amputation for shoulder girdle malignancies is not different
      from extremity soft tissue sarcomas or bone sarcomas located more distally. The
      morbidity and local recurrence rate after interscapulothoracic amputation should
      be negligible.

PMID- 8270042
TI  - Prognostic factors of gastric non-Hodgkin's lymphomas of the adult.
AB  - Sixteen patients, seven men and nine women, with a non-Hodgkin's lymphoma of the
      stomach (NHLS), have been managed in our institute during the past 15 years.
      Their median age was 68 years. Ten of them were classified, before treatment, at
      an early stage (I or II, Ann Arbor system) and six at an advanced one (III or
      IV). Ten patients were submitted to gastrectomy, and eight out of them had an
      adjuvant postoperative treatment (radiotherapy and/or chemotherapy). The
      remaining six patients were treated conservatively by radiotherapy and/or
      chemotherapy. Two patients that were followed less than 24 months were excluded
      from further study. In the remaining 14 patients, the 5-year actuarial and age
      corrected survival rates were 42% +/- 28 and 53% +/- 35, respectively. In the
      gastrectomy subgroup, the corresponding rates were 77% +/- 22 and 93% +/- 24. The
      later ameliorated results also, reflect the effect of an earlier stage. The most
      important prognostic factors appeared to be the stage and the histologic type.
      Old age and female sex seem to predispose to a better outcome, but they are not
      independent prognostic factors. Finally, a bad nutritional status, at
      presentation, seems an ominous prognostic sign.

PMID- 8270043
TI  - Histopathological assessment of tumoral destruction by alcoholization in an
      experimental model of human hepato-cellular carcinoma transplanted in nude mice.
AB  - This study aims to assess the efficacy of intra-tumoral alcoholization as a
      potential therapy against small hepatocellular carcinoma (HCC). The experimental
      model consisted of 20-mm diameter tumors resulting from subcutaneous abdominal
      injection of Hep G2 human hepatoma cell lines into nude mice (nu/nu).
      Alcoholization was performed using either a single centro-tumoral injection or
      multiple cross-shaped injections (tangential and oblique), during one sequence
      with a total dose of 0.1, 0.2 or 0.3 ml of 95% ethanol. Efficacy was assessed by
      the percentage of tumoral necrosis using a semi-quantitative method. Fifty-four
      tumors were alcoholized. Forty-eight hours following alcoholization, the tumor
      was regularly replaced by a necrotic ulcer. A single centro-tumoral injection
      always resulted in the persistence of a small peripheral edge of tumor cells even
      with the highest dose used (no dose-related effect). By contrast, the use of
      multiple injections restored a dose-related effect. Oblique cross-shaped
      injections of 0.3 ml of ethanol resulted in the highest mean tumoral necrosis
      rate (m +/- SD = 99 +/- 1%; range = 97-100). This study confirms that
      alcoholization is an efficient way to destroy hepatocarcinoma tissue and suggests
      that ethanol diffusion in HCC is less than 20 mm. In addition it demonstrates
      that increasing number and location of injections restores a dose-related effect,
      while efficacy is improved using oblique injections.

PMID- 8270044
TI  - Malignant branchioma--a further insight.
AB  - Two cases presented with solitary cystic mass in the usual position of a
      branchial cyst in the neck are reported. Histology on both cysts reported as
      carcinoma of a branchial cyst (malignant branchioma). In addition to pre
      operative radiotherapy to the neck, and ipsi-lateral radical neck dissection, the
      oropharynx is irradiated in prophylactic manner only in the second case. The
      first patient died of tonsillar carcinoma 3.5 years after diagnosis and the
      second case is well with no sign of recurrence 4 years after the initial
      diagnosis. The authors discuss the nature and management of the so called
      malignant branchioma.

PMID- 8270045
TI  - Successful surgical treatment of liver and kidney metastases 25 years after a
      primary lacrimal gland tumor.
AB  - Among primary lacrimal gland tumors the adenoid-cystic carcinoma is the most
      common malignant epithelial lesion. We present a unique case of hepatic and renal
      metastases surgically treated 25 years after excision of a primary adenoid-cystic
      carcinoma of the lacrimal gland and after resection of intracranial and pulmonary
      metastases. The clinical and pathological features of this malignant tumor are
      discussed. To our knowledge this is the longest reported survival of a patient
      with such a tumor.

PMID- 8270046
TI  - The National Institute of Oncology in Budapest. Introduction.

PMID- 8270047
TI  - Occult breast cancer presenting with axillary metastasis.
AB  - The literature of occult breast cancer is reviewed and the management of our 43
      patients is discussed. In 20 patients mastectomy and axillary block dissection,
      in nine upper-outer quadrant resection of the breast with axillary block
      dissection, and in two axillary biopsy were carried out. The primary tumour was
      found only in 11 patients during the first operation, either by macroscopic or
      microscopic examination. In 12 patients the primary breast tumour became
      detectable only later. Out of the 20 mastectomy specimens two primary tumours
      could not be identified even with the most thorough examination. In four patients
      of the breast conservation group the primary tumour remained occult until
      recently, and in the axillary block dissection group (12 patients) the site of
      the primary cancer could be identified only in two patients. The difficulties of
      the diagnosis and the dilemmas of the surgical indications and treatment are
      dealt with.

PMID- 8270048
TI  - Male breast tumours.
AB  - The data of 63 male breast cancer patients treated between 1967 and 1990 in the
      Department of Surgery of the National Institute of Oncology are described. Beside
      the 59 breast cancer cases four tumours of other histologic type were also
      detected. As to surgical treatment, in addition to mastectomy, the axillary block
      dissection is regarded as important in each case. The prognosis is mainly
      determined by the time elapsed until treatment and by the lymph node status. The
      mean survival of the axillary node negative patients was 116 months, compared to
      that of 38.9 months found in axillary node positive cases. Metastases were the
      soonest detected 2 years following surgery, altogether in 36 cases (61%). Local
      recurrence developed in eight patients (14%). Steroid hormone receptor
      investigations have been performed since 1980; of the 27 patients examined
      estrogen receptor positivity was seen in 25 cases. The hormone receptor study of
      the tumour and the assessment of the hormonal status of the patient provide
      valuable information for the treatment. In case of tumour progression the life of
      the patient might considerably be prolonged by combined hormone and cytostatic
      therapy.

PMID- 8270049
TI  - Preliminary evaluation of the use of the pectoralis major (PM) myocutaneous flap.
AB  - The modified PM myocutaneous flap was applied in 75 cases between 1982 and 1986
      for the closure of major defects of the oral cavity, meso- and hypopharynx and
      the neck region. Notwithstanding almost all of the patients had stage IV tumour,
      we had a good aesthetic and functional result. There was no total flap necrosis.
      In three cases the partial necrosis spontaneously regressed. The details of the
      operation techniques are compared with other reconstructive methods, the
      advantage of the PM flap is discussed.

PMID- 8270050
TI  - Vascular injuries in the surgical management of gynaecological malignancies.
AB  - From 1989 to 1991 we performed 184 radical gynaecological interventions. In the
      vast majority of the cases lymph node dissection was part of the procedure.
      Thirteen out of the 184 patients suffered vascular injury, accounting 7%
      complication rate. The sites of the injured vessels included the external iliac
      artery in four patients, the vena cava in three, the external iliac vein in five
      and the femoral vein in one patient. All of them were primarily sutured; no
      prosthesis or venous patch was needed. In four cases postoperative complications
      occurred in relation to vascular surgery: two deep thrombosis of the femoral vein
      and two occlusions of the external iliac artery. The latter two patients had
      permanent sequelae, i.e. difficulties in walking. Our study suggests that
      vascular injuries represent an utmost important intraoperative risk in the course
      of lymph node dissection in gynaecological malignancies. Thus, gynaecological
      surgeons performing radical operations must be prepared to deal with the problem.

PMID- 8270051
TI  - Perioperative complications of 116 radical hysterectomies and pelvic node
      dissections.
AB  - Perioperative morbidity and mortality were studied in 116 patients who underwent
      radical hysterectomy and lymph node dissection. Type II radical hysterectomy was
      performed in two, type III in 97, type IV in 12 and type V in five patients, and
      the perioperative morbidity was assessed accordingly. Because of the short follow
      up time the late sequelae could not be evaluated. There was no operative death.
      Haemorrhage was the most common complication and it was more frequent and serious
      in type IV and V classes. Prolonged bladder atony was also frequent, particularly
      in type IV radical hysterectomy. The infection rate was comparable. One patient
      developed ureteric fistula, and one woman had ureteric stricture. Lymphocyst
      formation, nerve damage, lymphoedema and thromboembolic disease were rarely
      encountered and there was no bowel obstruction. Injury to the great vessels was a
      major problem. It appears that the rate of complications in this study is
      acceptable and comparable with or favourable to other reported series. In spite
      of this, every effort should be made to reduce the operative morbidity as far as
      possible.

PMID- 8270052
TI  - Thoracic surgery of testicular cancer patients.
AB  - Between 1 January 1980 and 31 December 1991 the authors treated 1450 patients
      with malignant testicular tumours. Out of them, in 42 patients aged 18-43 years
      with stage III non-seminoma germ cell testicular cancer, thoracic surgical
      interventions took place on 44 occasions since the combined cytostatic treatment
      did not result in a sufficient regression, or disease progression occurred. In
      one case the lesion was inoperable. In 43 cases successful resection was
      performed. In 27 cases unilateral, in two cases bilateral thoracotomy and in 15
      cases median sternotomy took place. Solitary lesions were found in 26 and
      multiple ones in 18 cases, respectively. Two patients died in the direct
      postoperative phase. Forty patients were followed up for 4 to 130 months. Due to
      disease progression four and seven patients were lost within 12 and 12-24 months,
      respectively. Currently, 31 patients are alive 4 to 130 months following surgery
      (29 of them tumour-free, two with tumour). Based on adequate indications the
      thoracic surgery is justified both from diagnostic and therapeutic points of
      view. The metastasectomy might offer an advance in the management of these
      patients.

PMID- 8270053
TI  - Intraoperative colonoscopy.
AB  - The authors performed intraoperative colonoscopy in 31 patients. This examination
      is done if preoperative colonoscopy was not performed or incomplete, and
      intraoperative difficulty occurs. In addition, it is indicated to localize non
      palpable lesions, to perform polypectomy (if unsuccessful preoperatively but
      manageable intraoperatively), to define the site of endoscopic polypectomy, in
      certain instances to determine the resection plane, and after resection of
      constrictive tumours to look over the proximal intestinal section, to detect the
      synchronous lesions. It is emphasized that by their method the opening of the
      lumen becomes avoidable thus resulting in a decreased postoperative morbidity and
      mortality.

PMID- 8270054
TI  - Correlation between colon adenoma and cancer.
AB  - In the course of 1301 colonoscopies performed by the authors, in cases of 127
      patients (9.76%), 177 polyps were removed; 159 (89.83%) out of them proved to be
      adenomas by histology. In 23 adenomas (14.46%) malignant transformation was
      observed. The highest percentage of polyps was detected in the group of patients
      with tumours, and a somewhat lower proportion was found in the case of patients
      who underwent resection surgery because of tumours. A similar tendency could be
      seen concerning the malignant transformation of the removed adenomas. Our data
      seem to support the theory by Morson and Hermanek regarding the transformation
      from adenoma to cancer in the large bowel. Surgery is proposed in the following
      types of colon polyps: (1) polyps unremovable by endoscopic polypectomy, even by
      piecemal snare excision; (2) invasion (adenoma with invasive adenocarcinoma)--if
      the tumour is situated within a 3 mm distance from the resection line; (3)
      following endoscopic removal of polypoid adenocarcinoma (in this case the site of
      polypectomy can be marked by preoperative injection of ink or in the course of
      intraoperative colonoscopy); (4) in the case of complications of endoscopic
      polypectomy (perforation, bleeding uncontrollable by conservative or endoscopic
      means); (5) colotomy and polypectomy should be performed when the adenoma cannot
      be reached with the endoscope--for technical reasons--and the intraoperative
      method cannot be used under the conditions of an open abdomen but without the
      necessity of opening the bowel.

PMID- 8270055
TI  - Comparative evaluation of manual and instrumental rectum resections.
AB  - The authors compared the perioperative results of 125 + 125 Dixon operations
      performed at two time intervals (1956-1979 and 1985-1990), the postoperative
      recurrences and the survival data. It is established that, from the anastomosis
      point of view, the instrumental resections--beside their rapidity and favourable
      sterility--are safer interventions associated with less complications. With
      respect to local recurrences the two methods do not differ significantly. A
      further advantage of the double stapling is that a larger number of patients can
      undergo a sphincter-saving resection, and a lower lying anastomosis can be
      performed than with hand-sewn sutures.

PMID- 8270056
TI  - Ovarian metastases of colorectal tumours.
AB  - The authors, based on their own experience and review of the literature, discuss
      the incidence of ovarian metastases of patients with colorectal tumours. They
      take a stand for the prophylactic oophorectomy in the management of female
      patients over 40 years operated on for rectal cancer localized on the left colon
      side.

PMID- 8270057
TI  - Surgery of primary retroperitoneal tumours.
AB  - Upon detecting 112 retroperitoneal space-reducing processes the authors operated
      on 62 adults with primary retroperitoneal tumours (12 benign and 50 malignant).
      The diagnostics and complex therapy of these tumours are dealt with. It is
      established that although the CR, MRI and USG have resulted in a considerable
      development, the therapeutic results are still not much better. In the surgical
      management of benign lesions total tumour extirpation is recommended even with
      extensive multivisceral resections. For tumours of low grade malignancy the
      authors have the same standpoint. In case of PRTs of high grade malignancy--and a
      considerable number of patients belongs to this group--the ultraradical
      interventions are not associated with promising results and therefore are not
      recommended by the authors. In the complex management of primary retroperitoneal
      tumours the achievements of radio- and chemotherapy are nowadays rather only
      promising, rather than notable.

PMID- 8270058
TI  - Results of preoperative neoadjuvant chemotherapy and surgery in the management of
      patients with soft tissue sarcoma.
AB  - Between 1977 and 1991 653 patients were treated for soft tissue sarcoma. Since
      1985 limb saving surgery following preoperative neoadjuvant regional chemotherapy
      has taken place in 53 patients with stage III/A,B disease. In 56.6% (30 patients)
      treatment was indicated by tumour recurrence. Intra-arterial chemotherapy cycles
      were performed with doxorubicin (ADM) and cisplatin (cDDP) in the form of rapid
      infusion. In 25 patients (47%) partial or complete remission (PR,CR) and in 28
      patients (53%) minimal response (MR) could be observed. Following neoadjuvant
      therapy 52 patients underwent limb saving surgery. The patients were followed up
      for 3-77 months. Due to recurrence, reoperation was required in 22.4% of the
      cases (11/49 patients). Distant metastases developed in 32.6% (16/49 patients).
      No intraoperative mortality occurred, the perioperative mortality was 5.7% (three
      patients).

PMID- 8270060
TI  - Is the use of shunts in carotid endarterectomy still a problem?

PMID- 8270059
TI  - Thrombolysis in acute lower limb ischaemia.
AB  - For the past three decades balloon embolectomy has been the treatment of choice
      for acute lower limb occlusion. However, although usually successful in emboli,
      results are often disappointing in thrombotic atherosclerotic vessels. Attempted
      dissolution of the clot is accordingly attractive, and has theoretically been
      possible since the introduction of streptokinase in 1933. This was initially used
      intravenously, with variable success rates, although intraarterial administration
      is currently the method of choice. Later thrombolytic drugs such as tissue
      plasminogen activator, urokinase and anistreplase have been introduced. Lysis
      time has also been increased by using pharmaco-mechanical methods of
      administration such as pulsed spray catheters, which could increase the
      usefulness of thrombolysis in patients with rapidly progressive neurological
      signs where currently surgical embolectomy would be advocated. Several newer
      drugs with theoretical advantages over older drugs such as single-chain urokinase
      type plasminogen activator or K1K2PU are currently undergoing trials. The role of
      thrombolysis as an adjunct to surgical embolectomy is also promising, though
      again requires further trials. There is still no consensus as to which patients
      are best suited to thrombolysis, nor an optimum drug or method of administration.
      However, there seems no doubt that thrombolysis will be increasingly used in the
      management of peripheral limb ischaemia, though requiring a team approach between
      surgeons, radiologists and haematologists.

PMID- 8270061
TI  - Doppler spectral characteristics of infrainguinal vein bypasses.
AB  - With the aim of assessing the velocity profile of femoropopliteal and
      femorocrural vein bypasses, 128 patients undergoing infrainguinal vein bypass
      surgery entered a postoperative Duplex surveillance protocol, which included
      clinical assessment and Duplex scanning, using Doppler spectral analysis. Doppler
      spectra were obtained at three sites in each graft and the following waveform
      parameters recorded: maximum systolic velocity, minimum diastolic velocity and
      resistance index. In patent reconstructions systolic velocity decreased by 30%
      during the first 6 months after surgery. In the absence of arteriovenous fistulas
      the initially antegrade diastolic velocity was replaced by a retrograde flow
      within 3 months, whereas a forward flow in diastole was sustained in grafts with
      patent fistulas. Abnormal Duplex findings in 31 patients led to angiography and
      revision in 13 cases. Four revised grafts failed, while nine remained patent at
      follow-up 1-12 months later. Ten (56%) of 18 non-revised bypasses with abnormal
      Duplex findings failed within 9 months compared to 1 (1%) of 76 bypasses with a
      normal velocity profile (p < 0.00001). In conclusion, Ultrasound Duplex scanning
      with spectral analysis provides valuable information concerning haemodynamics of
      infrainguinal vein bypasses and identifies grafts at risk of thrombosis.
      Inclusion of low resistance index (< 0.75) as an additional criteria for
      detection of stenoses appears to improve the sensitivity of Duplex scanning.

PMID- 8270062
TI  - Detection of superior mesenteric and coeliac artery stenosis with colour flow
      Duplex imaging.
AB  - Measurements of blood velocity in the coeliac axis (CA) and the superior
      mesenteric artery (SMA) before and after a standard meal in normal people have
      been studied by several authors. However, information about the ability to detect
      stenotic lesions is lacking. The aim of our study was to determine the accuracy
      of Duplex scanning in detecting angiographically proven lesions. Twenty normal
      volunteers (13 males and seven females) and 24 patients (19 males and five
      females) with visceral artery stenosis on angiography were examined in the supine
      position (angle of insonation 60.5) with colour flow Duplex imaging (CFDI) (3.5
      MHz probe), in the fasting state and after a standard meal at 15, 40, 60 and 90
      min. Peak systolic velocity (PSV) and end diastolic velocity (EDV) were
      determined in both CA and SMA. The PSV was the best indicator of stenosis. After
      the meal, there was an increase in both PSV and EDV but neither of the
      postprandial measurements improved the accuracy of the test. The results indicate
      that CFDI can detect the presence of significant stenosis (> 50% in the CA and
      SMA with a sensitivity and specificity of > 80%.

PMID- 8270063
TI  - C-reactive protein and alpha-1-acid glycoprotein in monitoring of patients with
      chronic arterial occlusion of the lower limbs.
AB  - C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) levels were studied
      in the sera of 107 patients with chronic arterial ischaemia of the lower limbs.
      Depending on the degree of ischaemia, patients were divided into four groups: (i)
      intermittent claudication--20 patients; (ii) rest pain and ankle pressure above
      50 mmHg--12 patients; (iii) rest pain and ankle pressure below 50 mmHg--25
      patients; (iv) peripheral necrosis--50 patients. Reconstructive surgery was
      performed in 84 patients and primary major amputation in 23 cases. Levels of CRP
      and AGP increased with the severity of ischaemia. In uncomplicated cases, CRP and
      AGP concentrations decreased to normal values 7-10 days after surgery. In a group
      of 23 patients with postoperative necrotic complications, significant increases
      in CRP and AGP levels were found 7-10 days after surgery. These proteins,
      especially CRP, may be clinically useful in monitoring patients during the
      postoperative period with a CRP level greater than 50 mg/l predictive of
      complications with a sensitivity of 83% and a specificity of 94%.

PMID- 8270064
TI  - Modifications of the extracellular matrix of aneurysmal abdominal aortas as a
      function of their size.
AB  - Collagen and elastin are the main extracellular matrix proteins providing the
      aortic wall with adequate mechanical properties and resistance for proper
      function. Our study aimed at investigating the relationship between the elastin
      concentration of the wall of normal and aneurysmal abdominal aortas (AAA), the
      collagen concentration, and its extractability, as a function of their size.
      Infrarenal aortas were collected from 30 patients undergoing operative repair of
      abdominal aortic aneurysm. Age-matched control samples were obtained from eight
      autopsies of individuals without vascular disease. Samples were divided into five
      groups according to the aortic diameter: control group (group N, n = 8); < 50 mm
      (group I, n = 6; between 50-75 mm (group II, n = 10); > 75 mm (group III, n = 7);
      and ruptured (group IV, n = 7). The collagen concentration in samples from group
      I was similar to the controls. An increased collagen concentration was observed
      in group II and remained at the same level in the largest and ruptured aneurysms.
      Extractability of collagen was found to be increased in group III and was even
      higher in group IV. A highly significant reduction in elastin concentration was
      observed in group I and there was progressive reduction with increasing diameter
      and rupture. A significant correlation could be established between aortic
      diameter, increased collagen extractability and decreased elastin content.

PMID- 8270065
TI  - A national audit of antimicrobial prophylaxis in vascular surgery.
AB  - A standard questionnaire on antimicrobial prophylaxis for elective and emergency
      vascular surgery was sent to 262 practising members of the Association of
      Vascular Surgeons (U.K.). The response rate was 68.3%. A cephalosporin based
      regime was used in 61.1% of cases while penicillin was used in 39.3% and an
      aminoglycoside in 6.5%. More than one antibiotic was routinely used in 15.6% of
      cases, with specific anti-anaerobic cover in 19%. Prophylaxis was used in all
      cases using a prosthetic graft, but in only 76% of cases using autogenous vein (p
      < 0.05). A single dose regime was most commonly used for autogenous vein graft
      (14% vs. 4.5%, p < 0.05), whilst overall a three dose regime was most popular.
      Some 2.8% of respondents specified a differing regime for supra- and
      infrainguinal surgery whilst 4.5% modified their regime in emergency cases.
      Despite its theoretical limitations, a three dose cephalosporin regime is the
      most commonly prescribed "prophylactic" regime for all forms of vascular surgery
      in the U.K.

PMID- 8270066
TI  - Pre-bypass morphological changes in vein grafts.
AB  - Random vein samples taken prior to bypass surgery have shown certain pathological
      features. Long saphenous vein was taken from the groin (proximal) and knee to mid
      calf (distal) of 85 patients undergoing femoro-distal bypass over a 2-year
      period. During this period only four patients had cephalic arm vein used; this
      was also studied. Histological examination was performed using haematoxylin and
      eosin and van Geison stains. Intimal hyperplasia was seen in 62 (73%) proximal
      and 74 (87%) distal samples. There were significantly more distal veins with
      moderate to severe focal hyperplasia and circular muscle hypertrophy (p < 0.05
      and p < 0.001). Changes of diffuse intimal hyperplasia were seen in three of the
      cephalic veins. Muscle hypertrophy occurred in 58 (68%) of proximal segments
      compared to 75 (88%) of distal segments (p < 0.005). This study shows that
      significant pathological changes are seen in long saphenous and cephalic veins
      thought to be "normal". These changes are more evident in the distal long
      saphenous vein. These changes may have a significant effect on the outcome of
      vein bypass.

PMID- 8270067
TI  - Neuroendocrine and haemodynamic responses to abdominal aortic cross clamp and
      release during high-dose opiate-oxygen-isoflurane anaesthesia.
AB  - The haemodynamic and neuroendocrine responses and beta adrenoceptor distribution
      associated with aortic cross clamping and release were quantified in 14 patients
      undergoing elective abdominal aortic aneurysm surgery using a high-dose opiate
      oxygen-isoflurane anaesthetic technique. These changes were correlated with
      neutrophil beta adrenoceptor distribution. Aortic cross clamp application was
      associated with increased systemic vascular resistance (SVR), and decreased
      cardiac index (CI). Left ventricular stroke work index remained constant during
      the period of cross clamp application and following release. Cross clamp release
      was associated with increased CI and decreased SVR. Plasma cortisol
      concentrations did not change during the study period. Plasma catecholamine
      concentrations, although elevated prior to surgery, remained unchanged during
      aortic cross clamping and following release. The percentage of internalised beta
      adrenoceptors was elevated before surgery and was unaffected by surgical
      intervention. This study suggests that a high-dose fentanyl-oxygen-isoflurane
      anaesthetic technique in a patient population with high circulating catecholamine
      levels and downregulation of beta adrenoceptors is associated with cardiovascular
      stability and attenuated neuroendocrine responses.

PMID- 8270068
TI  - Skin microcirculation in diabetic and non-diabetic patients at different stages
      of lower limb ischaemia.
AB  - One hundred and one non-diabetic and 54 diabetic patients suffering from lower
      limb ischaemia were divided into (i) asymptomatic subjects, (ii) claudicants,
      (iii) critically ischaemic patients, i.e. Fontaine III or IV patients with either
      an ankle pressure < 51 mmHg or a toe pressure < 31 mmHg, and (iv) Fontaine III or
      IV patients in whom ankle and toe pressures could not be assessed due to vessel
      wall sclerosis or skin ulceration. Skin microcirculation was investigated to
      assess (a) the compounding effect of diabetes in leg ischaemia and (b) the
      additive value of microcirculatory investigation in the appreciation of the
      severity of the ischaemic disease. The techniques used included capillary
      microscopy, transcutaneous oximetry and laser Doppler fluxmetry. The severity of
      ischaemia was readily discernable using microcirculatory techniques. The presence
      of diabetes appeared to change skin microcirculatory perfusion, but especially in
      critically ischaemic patients, the microcirculation was no more compromised than
      non-diabetics. Using skin oxygen tension measurements, a positive predictive
      value of 77% was obtained in the detection of critical ischaemia, when a cut-off
      value of 30 mmHg was applied. Seventy per cent of patients, in whom the severity
      of ischaemia could not be classified using blood pressure measurements, could be
      classified as critically ischaemic on the basis of microcirculatory
      investigation. In conclusion, the influence of diabetes on the microcirculation
      is outweighed by the effects of atherosclerosis when vascular disease becomes
      severe. Techniques to investigate skin microcirculation are a useful way of
      assessing the severity of lower limb ischaemia in the presence of diabetes
      mellitus or if peripheral blood pressures cannot be obtained.

PMID- 8270069
TI  - Biomechanical factors in abdominal aortic aneurysm rupture.
AB  - Hitherto the size of abdominal aortic aneurysms (AAA) has been considered the
      most important factor in determining the risk of rupture. For this reason most
      interest has been devoted to physical, echographic and tomographic analyses of
      the shape of AAA. However, it is known that rupture can also occur in small AAA.
      Other factors must be considered to have an important role in the natural history
      of aneurysms. The aim of this study was to characterise the mechanical stress in
      the wall of an AAA due to pressure in the presence of atherosclerosis,
      intraluminal thrombus and anatomical restraints. The Finite Elements Method (FEM)
      was used to determine wall stress distribution. Due to the simplicity of the AAA
      structure an axisymmetric model has been built. The results of the structural
      analysis confirms that maximum stress increases with diameter. These effects may
      be reduced by the presence of intraluminal thrombus, which in the models reduces
      maximum stress by up to 30%; however this is not the case for dissecting
      thrombus. On the other hand atherosclerotic plaques cause stress concentration
      and a significant increase in maximum wall stress. The risk of rupture can
      increase by about 200%. Finally the investigation shows the FEM is a versatile
      tool for studying the mechanics of vascular structures. It enables the influence
      of various parameters on wall stress to be quantified in diagnostic settings, and
      so could be useful for predicting the rupture of AAA, although at present such
      predictions are limited by data leakage and by the approximations used in the
      model.

PMID- 8270070
TI  - In vivo demonstration of focal fibrinolytic activity in abdominal aortic
      aneurysms.
AB  - Disseminated intravascular coagulation in association with arterial aneurysm has
      been reported in several cases. Reports have suggested a continuous deposition of
      fibrin and/or platelets at the site of the aneurysm followed by fibrinolysis as
      responsible for this disorder. To further investigate this theory we studied the
      in vivo binding of an indium-111-labelled monoclonal antibody against human
      tissue plasminogen activator (t-PA), a proteolytic enzyme involved in the
      fibrinolysis. Six patients admitted to the hospital for elective resection of an
      abdominal aortic aneurysm with a mural thrombus were examined. One day before the
      operation the antibody was injected intravenously. Scintigrams acquired just
      prior to operation and tissue samples obtained at the operation revealed an
      increased t-PA accumulation in the wall of the aneurysm. The study demonstrates
      in vivo, focally increased fibrinolytic activity in the aneurysm, explaining the
      coagulopathy observed in these patients.

PMID- 8270071
TI  - Femoropopliteal occlusions and the adductor canal hiatus, Duplex study.
AB  - The majority of lower limb arterial occlusions are located in the distal third of
      the thigh. However, the exact location of occlusions in relation to the
      surrounding anatomy has never been examined. Duplex ultrasound was used to
      determine the location of femoropopliteal occlusions in 50 patients by comparing
      the level of occlusions to the level of the adductor canal hiatus. We found that
      although the level of the adductor canal hiatus may vary, 72% of occlusions are
      related to the site of the adductor canal hiatus. Short occlusions were located
      in the hiatus region, longer occlusions extended mainly in the proximal
      direction.

PMID- 8270072
TI  - Level of arterial obstruction in patients with peripheral arterial occlusive
      disease (PAOD) determined by laser Doppler fluxmetry.
AB  - AIM: To evaluate the laser Doppler fluxmeter as a non-invasive screening method
      to determine the level of peripheral arterial occlusive disease (PAOD) in the
      lower limb. DESIGN: Open study of the veno-arterial reflex (VAR) during a shift
      in body position using a laser Doppler fluxmeter at five probe positions distal
      to the knee, compared with the occlusion level determined by arteriography and
      segmental plethysmography. MATERIALS: 50 legs comprising 10 normal controls, 20
      legs with suprainguinal obstructions (10 claudication and 10 critical ischaemia)
      and 20 legs with infrainguinal obstructions (10 claudication and 10 critical
      ischaemia). RESULTS: Controls had normal VAR (mean flux reductions of 38% during
      dependency) at all probe positions. Legs with infrainguinal disease had normal
      reflexes proximally but significantly disturbed reflexes distally, whereas
      suprainguinal disease showed alterations at all sites. Claudicants had diminished
      flux reduction (mean 12%) whilst those with critical ischaemia increased the flux
      (mean 32%). CONCLUSION: This simple, non-invasive technique may be of use in
      determining the level of obstruction in PAOD.

PMID- 8270073
TI  - Compliance and diameter in the human abdominal aorta--the influence of age and
      sex.
AB  - OBJECTIVES: Females develop cardiovascular diseases and abdominal aortic
      aneurysms later in life than males. In this study we investigated the diameter
      and compliance of the distal abdominal aorta in healthy females of varying ages.
      The results were compared with those obtained previously from healthy males in
      order to assess potential sex-related differences in the aging process of the
      abdominal aorta. METHODS: An ultrasound phase-locked echo-tracking system was
      used to determine differences in diameter and pulsatile diameter change of the
      distal abdominal aorta in 69 Caucasian females from 4 to 74 years. Pressure
      strain elastic modulus (Ep) and stiffness (beta) were calculated from diameter,
      pulsatile diameter change and blood pressure obtained by the auscultatory method.
      Compliance was defined as the inverse of Ep and beta. The pressure dependence of
      Ep and beta was evaluated in 10 females with intraarterial blood pressure
      measurement at rest and during isometric exercise. RESULTS: The diameter of the
      distal abdominal aorta increased not only in the period between the ages of 5 and
      25 years, but also by about 24% between 25 and 70 years (p < 0.0001). From about
      the age of 25 years the diameter was smaller in females than in males (p < 0.01).
      Ep and beta increased nearly linearly with advancing age in females from 0.18 x
      10(5) to 1.17 x 10(5) N/m2 (Ep) and from 1.85 to 8.51 (beta). In males the
      increase in Ep and beta was greater and exponential in nature (p < 0.001). Ep but
      not beta increased significantly during blood pressure increase (p < 0.05).
      Stiffness (beta) may therefore be a more useful index of arterial compliance than
      Ep. CONCLUSIONS: This investigation demonstrates age and sex-related differences
      in diameter and compliance in the normal human abdominal aorta and implies that
      degenerative changes appear later in females than in males.

PMID- 8270074
TI  - The uptake of platelets, fibrinogen and leucocytes in ePTFE vascular grafts in
      relation to blood flow--an experimental study in sheep.
AB  - The uptake of platelets, fibrinogen and leucocytes in relation to blood flow was
      studied in ePTFE arterial grafts inserted in both common carotid arteries of 10
      adult sheep. Autologous platelets labelled with In-111, autologous leucocytes
      labelled with Tc-99m and homologous fibrinogen labelled with I-125 were used. The
      leucocyte uptake was studied in five of the animals. The uptake was measured with
      a gamma scintillation technique. The blood flow in the graft on one side was
      restricted to 25 ml/mm, and in the other graft the blood flow was unrestricted
      (median 170 ml/min). One out of 10 grafts in the reduced flow group occluded but
      none of the grafts in the unrestricted flow group. The mean thrombus weight was
      significantly higher in the reduced unrestricted flow (0.28 vs. 0.19 g). At the
      proximal anastomosis the uptake of platelets, fibrinogen and leucocytes was
      higher in the reduced than unrestricted flow. The differences were significantly
      higher for fibrinogen for the whole duration of the experiments and for platelets
      and leucocytes during the last 48 min. Distally the platelet and fibrinogen
      uptake were higher in the reduced than in unrestricted flow. The leucocyte uptake
      did not differ distally. The differences were significant for fibrinogen for the
      whole duration of the experiments and for platelets during the last 120 min. A
      comparison between the proximal and distal anastomosis showed a higher uptake
      distally.

PMID- 8270075
TI  - Prediction of early graft occlusion in femoropopliteal and femorodistal
      reconstruction by measurement of volume flow with a transit time flowmeter and
      calculation of peripheral resistance.
AB  - A transit time flowmeter (Transonic TC101DTM, Transonic Inc., U.S.A.) was used
      for flow measurements and calculation of peripheral resistance in 48 primary
      femoropopliteal and femorodistal reconstructions. The results were correlated
      with primary graft occlusions during the first 90 postoperative days. There were
      25 men and 23 women with a median age of 75 years (67-83). Eight were diabetic.
      Indications for surgery were rest pain (n = 23), ischaemic ulcer (n = 16),
      gangrene (n = 8) and popliteal aneurysm (n = 1). Measurements were made before
      reconstruction on the artery at the site of the distal anastomosis. After
      reconstruction flow measurements were made on the graft near the proximal and
      distal anastomoses together with a proximal graft pressure measurement. The
      peripheral resistance was calculated. Eleven grafts occluded and six patients
      died, four with patient grafts. Patients with graft occlusions had a
      significantly lower flow before (4 vs. 20 ml/min) and after (60 vs. 110 ml/min)
      reconstruction and a higher peripheral resistance, (1238 vs. 625 mPRU) than
      patients with patent grafts. The most significant differences were found in the
      femorodistal bypass grafts. The transit time flowmeter was easy to use. The flow
      before and after reconstruction as well as the peripheral resistance could be
      used for the prediction of graft function within 90 days of surgery.

PMID- 8270076
TI  - Familial abdominal aortic aneurysm: prevalence and implications for screening.
AB  - The high prevalence of abdominal aortic aneurysm (AAA) in men over the age of 65
      has led to the establishment of ultrasound screening programmes for this group.
      The apparent familial tendency towards AAA formation suggests that relatives of
      aneurysm patients may form another subpopulation in whom screening is
      appropriate. The first degree relatives of 100 consecutive aneurysm patients were
      identified. Of 110 relatives over 50 years of age, two were known to have had AAA
      and ultrasound scans were performed on 74, providing information on aortic size
      for 76 relatives (69%). No further aortic aneurysms (antero-posterior diameter >
      or = 4.0 cm) were found on scanning. However, nine relatives were demonstrated to
      have aortic dilatation (2.5-3.9 cm). Aortic dilatation was observed in 21% of
      male first degree relatives over 50 years of age, affecting 27% of sons and 17%
      of brothers. Only 4% of the sisters and none of the daughters were found to have
      aortic dilatation. The prevalence of aortic enlargement seems to be sufficiently
      high amongst male first degree relatives of AAA patients over 50 years of age to
      justify aortic screening.

PMID- 8270077
TI  - Colour Duplex imaging through wound dressings.
AB  - Colour flow Duplex scanning is becoming the method of choice to determine patency
      and haemodynamic status in infrainguinal grafts and native arteries. Due to
      surgical wounds and ulcers, there are often dressings covering the leg above the
      vessel to be scanned. There is no data as to the effect of different wound
      dressings on colour flow Duplex signals. Ten normal superficial femoral arteries
      were scanned by a blinded operator. Initially the artery was visualised to assess
      the normal image produced for each artery on B-mode and colour flow ultrasound
      and a Doppler reading was taken. Then each of five commonly used dressings were
      applied to the skin above the artery, in random order and the blinded operator
      graded the signal produced on a linear analogue scale. Primapore, an absorbent
      material dressing and Spyroflex, a bilaminate membrane dressing, did not transmit
      ultra-sound at all. Granuflex extra thin allowed a clear B-mode image of each
      artery to be visualised and an adequate Doppler waveform to be obtained. However
      colour flow mapping was less than optimal although it was possible in each of the
      arteries. Opsite and Tegaderm, two thin membrane dressings allowed excellent B
      mode and colour flow images, in addition to clear Doppler signals. In patients
      who require dressings and who may require colour flow Duplex scanning of vessels
      in the same area, we would suggest the use of a product that permits ultrasound
      transmission, thus saving the necessity of removing the dressing for the
      assessment.

PMID- 8270078
TI  - The differences in early haemodynamic response between surgery and angioplasty
      after successful re-opening of the superficial femoral artery.
AB  - In 40 patients with superficial femoral artery disease we prospectively evaluated
      the effect of angioplasty (n = 20) or femoropopliteal bypass (n = 20) on the
      ankle-brachial pressure index (ABI) using the Doppler ultrasound probe. The ABI
      was measured as a baseline 1 day before the procedure, 1 day after the procedure
      and 30 days later. In the angioplasty group the baseline ABI was 0.57 (0.11),
      increasing to 0.74 (0.26) 1 day postangioplasty and increasing further to 0.88
      (0.26) after 30 days. The increase in ABI over 30 days was significantly greater
      than the increase over 1 day. In the femoropopliteal bypass group the baseline
      ABI was lower at 0.46 (0.17). However 1 day postoperatively it had increased to
      0.92 (0.2) with almost no further increase at 30 days [0.95 (0.17)]. We concluded
      that by contrast to a surgical bypass where there was a large improvement in the
      ABI over the first day, the ABI following angioplasty continued to improve
      significantly beyond the first day.

PMID- 8270079
TI  - Cross-linked fibrin degradation products (XL-FDP) as marker of early rethrombosis
      in percutaneous transluminal angioplasty.
AB  - The thrombotic response to percutaneous transluminal angioplasty (PTA) was
      investigated in 31 patients treated for 1-10 cm femoropopliteal (n = 28) and
      tibial (n = 3) artery obstructions by measurement of cross-linked fibrin
      degradation products (XL-FDP) in peripheral blood samples drawn before and 30 min
      after PTA. XL-FDP increased from 400 +/- 147 ng/ml to 700 +/- 445 ng/ml (median
      +/- S.E., p = 0.0005). XL-FDP rose from 320 +/- 110 ng/ml to 540 +/- 102 ng/ml in
      23 patients, whose ankle/brachial systolic blood pressure index (ABI) increased >
      0.15 after PTA, whereas XL-FDP increased from 850 +/- 450 ng/ml to 2620 +/- 1472
      ng/ml in eight patients, who failed to increase ABI in spite of preceding
      recanalisation. XL-FDP increased by more than 1000 ng/ml in 1/23 (4.3%) patients
      with uncomplicated PTA and in 6/8 (75%) patients with haemodynamic failure (p =
      0.0005). Using a XL-FDP increase of 1000 ng/ml as cut-off, estimates of positive
      and negative predictive values (95% confidence limits) for early failure of PTA
      were 85.7% (42.1-99.6%) and 91.7% (73.0-99.0%), respectively. We conclude from
      this pilot study that femorotibial PTA produces a hypercoagulable state which may
      result in failure of early patency due to rethrombosis. We suggest for the first
      time XL-FDP as a marker of early rethrombosis in PTA, and report a sequential XL
      FDP assay which may be useful for identification of high-risk patients requiring
      thrombolytic therapy after PTA for maintenance of early vascular patency.

PMID- 8270080
TI  - An aggressive approach to acute superior mesenteric arterial ischemia.

PMID- 8270081
TI  - The transtibial route for femoral to anterior tibial artery bypass.
AB  - OBJECTIVE: To assess the applicability of the transtibial route, via a drilled
      hole in the tibia, for femoral to anterior tibial artery bypass surgery. DESIGN:
      in a pilot study of 10 patients the preoperative arm/ankle systolic blood
      pressure indices were compared with those after operation. Patients were followed
      for 2 years. RESULTS: of the 10 patients, one was lost to follow-up and two had
      occlusions of their bypasses. After two years the remaining seven still had
      patient bypasses, with arm/ankle systolic blood pressure indices that were
      significantly higher than those before operation (p < 0.05). CONCLUSION: The
      transtibial route, via a drilled hole in the tibia, is a viable alternative to
      other methods for femoral to anterior tibial artery bypass surgery.

PMID- 8270082
TI  - Tibial artery thrombectomy facilitated by guidewire placement of the thrombectomy
      catheter.

PMID- 8270083
TI  - Aortic aneurysm leak after streptokinase treatment for myocardial infarction.
AB  - A leak from an abdominal aortic aneurysm following the administration of
      streptokinase treatment for myocardial infarction is reported. It is important to
      assess candidates for cardiac thrombolytic therapy for aortic pathology and give
      such treatment with extreme caution in those patients with abdominal aortic
      aneurysms.

PMID- 8270084
TI  - Fibromuscular dysplasia and aneurysm formation in the brachial artery.
AB  - A patient with isolated right brachial artery aneurysms is presented. As a young
      woman these had been misdiagnosed, leading to inappropriate surgery and a
      subsequent brachial artery aneurysm produced median nerve neuropraxia. Resection
      of the aneurysm and bypass relieved these symptoms and the aetiology was
      fibromuscular dysplasia. The literature on fibromuscular dysplasia and aneurysms
      of the brachial artery are reviewed.

PMID- 8270085
TI  - The treatment of upper limb vascular occlusions using intraarterial thrombolysis.
AB  - Acute ischaemia of the lower limb is increasingly treated by intraarterial
      thrombolysis. Four cases are reported in which this technique has been used
      successfully for treatment of upper limb emboli. The possible indications and
      potential drawbacks of such treatment are discussed.

PMID- 8270086
TI  - False aneurysm formation of the right common femoral artery: a rare complication
      of a Salmonella infection.
AB  - We present a case history of a patient admitted with a Salmonella infection of
      the lymph nodes in the right groin. After 5 days a false aneurysm of the right
      common femoral artery developed. The patient was successfully treated with an
      extra-anatomic (obturator) bypass, isolation of the aneurysm, and local as well
      as systemic antibiotic therapy.

PMID- 8270087
TI  - Acute ischaemia of the lower limb: an unusual presenting feature of acute
      lymphoblastic leukaemia.
AB  - Malignant disease is often complicated by coagulation disorders presenting as
      abnormal clotting or bleeding, acute leukaemia being more often associated with
      the latter. Acute lymphoblastic leukaemia presenting with peripheral arterial
      thromboembolism, previously unreported in the literature, is presented.
      Aetiology, clinical features, and management of coagulation disturbances
      associated with malignancy are also reviewed.

PMID- 8270088
TI  - Successful salvage of an exposed axillopopliteal prosthetic graft using three
      muscle flaps in sequence.

PMID- 8270089
TI  - Long saphenous vein saving surgery for varicose veins.

PMID- 8270090
TI  - Analysis of the attraction of haemocytes from Mytilus edulis by molecules of
      bacterial origin.
AB  - Boyden chamber assays were performed to test the stimulatory effect of different
      bacterial products on the migratory activity of Mytilus haemocytes. The results
      indicate that these blood cells exhibit chemotactic as well as chemokinetic
      reactions. Lipopolysaccharides (LPS) from both Serratia marcescens and
      Escherichia coli stimulated the migration of cells through the membrane of the
      Boyden chamber when LPS was present in the lower compartment only. In contrast,
      addition of LPS to the lower as well as to the upper chamber did not increase the
      rate of migrating cells. Thus, LPS seemed to act as a chemotaxis-stimulating
      substance. Further analysis indicated that complete LPS molecules are required
      for cell stimulation because this did not occur when either the lipid or
      polysaccharide moieties of LPS were tested alone. Unlike LPS, the formylated
      tripeptide N-FMLP stimulated random cell migration. The peptide, which is
      released by bacteria, induced a higher haemocyte motility when present in both
      wells of the Boyden chamber than in tests where it was added to the lower
      compartment only. This chemokinetic response was not stimulated by the
      tetrapeptide N-FMLPLys. These findings demonstrate that bacterial products may
      elicit chemotactic and/or chemokinetic reactions in haemocytes from an
      invertebrate, and that the type of reaction that occurs is dependent upon the
      nature of the molecules presented.

PMID- 8270091
TI  - Morphological and biochemical characterization of Procambarus clarki blood cells.
AB  - Morphological and cytochemical analysis of Procambarus clarki hemocytes
      demonstrated three cell types: hyaline, semigranular, and granular. Hyaline cells
      showed a higher nuclear/cytoplasmic ratio with few small electron-dense granules
      in the cytoplasm. Semigranular cells presented numerous round or oval
      eosinophilic granules (0.40-0.78 micron). Granular cell contained large
      eosinophilic granules (1.79-3.05 microns). Ultrastructurally, all cells showed
      microtubules near the borders, a poorly developed Golgi complex, and secretory
      type electron-dense particles. No mitotic figures were seen. Cell monolayers
      showed three morphologically distinct cell types (composed of flattened and well
      spread cells) depending on the presence and size of granules (hyaline,
      semigranular, and granular). No sex-related differences could be documented in
      cell features or proportions. Cytochemical studies showed that the three cell
      types were positive for acid phosphatase. Granular and semigranular cells were
      also positive for nonspecific esterase. Phenoloxidase activity was localized only
      in granular and semigranular hemocytes, and peroxidase activity was observed only
      in the granular hemocytes. These results may suggest that the semigranular and
      granular hemocytes participate in the prophenoloxidase system and also in
      phagocytic or cytotoxic function.

PMID- 8270092
TI  - Prophenoloxidase system activation in the crayfish Procambarus clarki.
AB  - The prophenoloxidase system (proPO) was studied in primary cultures of hemocytes
      of the crayfish Procambarus clarki. Both zymosan and lipopolysaccharide (LPS)
      separately induced rapid degranulation and lysis of semigranular hemocytes, with
      concurrent release of proPO. ProPO could be demonstrated in the hemocyte lysate
      supernatant (HLS) obtained by a freeze/thaw method, and was specifically
      activated by LPS and zymosan. Phenoloxidase activity was blocked by serine
      protease inhibitors, such as soybean trypsin inhibitor (STI), leupeptin, and
      phenylmethyl-sulphonylfluoride (PMSF), and substantially increased by cysteine
      protease inhibitors (N-methylmaleimide, N-ethylmaleimide, and iodoacetamide).
      This enhancement was observed only when the proPO system was activated.
      Incubation without activators or preincubation with STI prevented the induced
      enhancement. Electrophoretic analyses of HLS treated with zymosan or LPS showed
      that three bands at 41, 39, and 37 kDa were specifically modified when the system
      was activated. These results suggest that a serine protease is involved in the
      activation of the proPO system in P. clarki, and a mechanism susceptible to
      cysteine protease inhibitors could be related to its regulation.

PMID- 8270093
TI  - Isolation and characterization of a hemagglutinin with affinity for
      lipopolysaccharides from plasma of the crayfish Pacifastacus leniusculus.
AB  - A hemagglutinin with a high specific activity against trypsinized rabbit
      erythrocytes was identified in plasma of the freshwater crayfish Pacifastacus
      leniusculus. The activity of this crayfish hemagglutinin could be inhibited by
      sialoglycoproteins such as porcine stomach mucin, bovine submaxillary mucin,
      fetuin, and ovalbumin. However, the involvement of sialic acid in its binding
      specificity could not be unambiguously proven. Furthermore, the hemagglutinating
      activity in the crayfish plasma could be specifically inhibited by
      lipopolysaccharide from E. coli K-235, which might indicate a recognition role
      for this hemagglutinin. This hemagglutinin, which accounts for less than 0.01% of
      the total plasma protein, was purified to near homogeneity using affinity
      chromatography on a Fetuin-Sepharose 4B column. The molecular mass of the
      unreduced protein as revealed by sodium dodecyl sulphate electrophoresis in
      polyacrylamide gel was found to be 420,000 Da. Upon reduction with dithiothreitol
      the hemagglutinin dissociated to several subunits with masses ranging from 65,000
      to 80,000 Da. Affinoblotting with peroxidase labelled lectins indicated that the
      hemagglutinin was likely to be a glycoprotein.

PMID- 8270094
TI  - Ontogeny of IgM and IgM-bearing cells in rainbow trout.
AB  - We have studied the ontogenic development of immunoglobulin M (IgM) and of IgM
      bearing cells in the rainbow trout, Oncorhynchus mykiss. Lymphocytes showing
      cytoplasmic IgM were first observed in embryos at 12 days before hatch (14
      degrees C). At this stage, no cells positive for surface IgM were present.
      Lymphocytes bearing surface IgM were observed at 8 days before hatch (14 degrees
      C). Unfertilized trout eggs contained detectable amounts of IgM (11.2 +/- 2.6
      micrograms/g of egg weight), indicating that transfer of IgM from mother to
      embryo can occur in salmonids. The levels of IgM from whole fish increase slowly
      after the appearance of intraembryonic cells that express surface IgM. The amount
      of IgM/g of tissue peaks around hatch, but this parameter shows lower values up
      to 2 months after hatch.

PMID- 8270095
TI  - Demonstration of cells involved in rejection of tolerogenic grafts in tolerant
      Xenopus.
AB  - The J-strain (JJ) clawed frog, Xenopus laevis, can easily be made tolerant of
      semixenogeneic (X. laevis x X. borealis; JB) adult skin grafted onto larvae
      before stage 57 (larvally induced tolerance). To examine the cellular bases of
      this tolerance, we have established a simple and reliable method of quantifying
      the proliferating splenocytes in vivo by using BrdU and anti-BrdU antibody. When
      adult JJ frogs were injected with adult JB peripheral blood cells (PBCs), host
      splenic lymphocytes proliferated even in frogs that were tolerant of JB skin.
      Splenic lymphocytes from animals primed in vivo with JB PBCs were injected into
      early thymectomized (Txd) frogs that carried previously grafted JB skin. In Txd
      frogs injected with splenocytes from normal frogs, the rejection of JB skin
      grafts was initiated promptly and ended in about 10 days. Rejection was
      relatively delayed in the frogs injected with splenocytes depleted of
      proliferating cells, suggesting that the proliferating cells were actively
      involved in the rejection process. Early Txd frogs injected with splenocytes from
      undisturbed tolerant donors did not reject JB skin grafts. Quite unexpectedly,
      all five early Txd frogs, injected with undepleted splenocytes from tolerant
      donors previously stimulated with JB PBCs, rejected the JB skin grafts, four of
      them subacutely. In frogs injected with the splenocytes from PBC-injected
      tolerant donors that had been depleted of proliferating cells, the rejection was
      delayed. The most likely explanation is that cells actively involved in graft
      rejection exist in tolerant frogs and can be stimulated to proliferate, although
      cytotoxicity of the graft is usually suppressed or disabled by unknown
      mechanisms.

PMID- 8270096
TI  - Identification and partial characterization of common seal (Phoca vitulina) and
      grey seal (Haliochoerus grypus) interleukin-6-like activities.
AB  - Interleukin-6 (IL-6) is a pleiotropic molecule with many important immune
      modulatory actions. We have investigated the production of biological activity of
      this cytokine in two species of European seal. IL-6-like activity was detected in
      supernatants from cultured peripheral blood leucocytes. This IL-6-like activity
      had an apparent molecular weight of 17-26 kDa, similar to that of human IL-6. IL
      6-like activity was also detected in plasma taken from seals with symptoms of
      systemic infection, but not from apparently healthy seals. Inhibition of this
      plasma and leucocyte derived activity was accomplished with both rabbit and goat
      antisera raised against recombinant human IL-6. Further investigation using
      polymyxin-B showed that this activity was not due to residue LPS present in the
      supernatants or infected plasmas.

PMID- 8270097
TI  - International meeting on transmissible spongiform encephalopathies--impact on
      animal and human health. Heidelberg, Germany, June 23-24, 1992. Proceedings.

PMID- 8270098
TI  - Analysis of BSE risk factors in Argentina.

PMID- 8270099
TI  - Scrapie control in the United States: a review of the past with an emphasis on
      the present Flock Certification Program.

PMID- 8270100
TI  - Epidemiologic and experimental studies on transmissible mink encephalopathy.
AB  - Transmissible mink encephalopathy (TME) is a rare foodborne disease of ranch
      raised mink produced by an as yet unidentified contaminated feed ingredient.
      Because of the clinicopathologic similarities to scrapie and the
      indistinguishable physicochemical properties of their transmissible agents, it
      was initially assumed that TME was caused by feeding mink scrapie-infected sheep.
      However, subsequent studies testing the oral susceptibility of mink to scrapie
      were unsuccessful. Epidemiologic investigations of individual incidents of TME
      have not identified an association between the occurrence of disease and the
      feeding of any particular ingredient. However, there are two incidents in which
      the rancher was confident that sheep were not fed. The most recent of these was
      in Stetsonville, Wisconsin in 1985 where the meat portion of the diet was
      composed almost exclusively of downer dairy cows. To examine the possibility that
      cattle may have been the source of infection on the Stetsonville ranch, mink
      brain was experimentally inoculated intracerebrally into two Holstein steers.
      Both of these animals developed fatal spongiform encephalopathies 18 and 19
      months after inoculation. These findings are compatible with the Stetsonville
      incident of TME being caused by feeding mink infected cattle tissue and they
      suggest the presence of an unrecognized BSE-like disease in the United States.
      Further experimental studies on the Stetsonville source of TME have identified
      two distinct strains of the transmissible agent in Syrian hamsters. These strains
      vary in length of incubation period, clinical signs, endstage brain infectivity
      titre, and pathogenicity for mink.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270101
TI  - Surveillance for lesions of bovine spongiform encephalopathy in U.S. cattle.
AB  - The appearance of bovine spongiform encephalopathy (BSE) as a new disease of
      cattle in 1985-1987 increased worldwide interest in various aspects of human and
      animal spongiform encephalopathies. In the United States, a part of the
      surveillance effort has been directed toward prospective examination of bovine
      brain specimens for lesions of BSE. One focus area has been to obtain specimens
      from cattle that (1) are two years of age or older, (2) have documented signs of
      neurologic disease, and (3) have received protein supplement as a substantial
      part of the i.v. ration. Another focus area has been to examine rabies-suspect
      cases that were rabies-negative. A third area has been to obtain the results of
      bovine neuropathology examinations being conducted at other state and regional
      laboratories. Specimens have been obtained by direct submission and by referral
      from other public health and veterinary diagnostic laboratories. Many of the
      cases have been classified as having (1) inflammatory lesions such as
      listeriosis, pseudorabies, brain abscesses and inflammation of undetermined
      cause, (2) degenerative lesions such as polio-encephalomalacia, lead poisoning,
      Wallerian degeneration, siderocalcinosis, and lipofuscinosis, (3) neoplastic
      lesions such as meningioma and Schwannoma, and (4) no significant findings. Other
      case results were reported as inflammation or no significant findings. Of the 459
      cases reported here none has contained lesions with the characteristics and
      distribution typical of BSE.

PMID- 8270102
TI  - Early clinical and laboratory diagnosis of Creutzfeldt-Jakob disease.

PMID- 8270103
TI  - Foreign PrP expression and scrapie infection in tissue culture cell lines.
AB  - PrP expression and scrapie infectivity was studied in a group of tissue culture
      cell lines from mice, hamsters, rats and humans. Cell surface PrP protein was
      detected in seven of ten cell lines from a variety of tissues and showed both
      cell surface and cytoplasmic perinuclear distributions. Mouse N2a neuroblastoma
      cells could be persistently infected with scrapie in vitro, but OBL-21 mouse
      neuroma cells were never successfully infected. Foreign PrP molecules including
      hamster PrP, mutant hamster PrP with leucine at amino acid 102, and mutant mouse
      PrP expressing a hamster-encoded PrP antigen epitope were expressed in mouse N2a
      cells. However, none of these cell lines could be successfully infected with the
      263K hamster scrapie agent. Furthermore, expression of these foreign PrP
      molecules did not lead to spontaneous generation of protease-resistant PrP or a
      transmissible scrapie-like agent in vitro.

PMID- 8270104
TI  - The role of antibodies to PrP in the diagnosis of transmissible spongiform
      encephalopathies.
AB  - Transmissible spongiform encephalopathies (TSE) are progressive degenerative
      disorders of the central nervous system. Efficient and accurate identification of
      these disorders is necessitated by their transmissibility and fatal prognosis.
      The availability of polyclonal and monoclonal antibodies to a TSE disease
      specific protein marker PrPSC affords the sensitivity and specificity for immuno
      diagnostic assays. The majority of PrPSC antigenic sites are species-directed,
      involve non-self sites and are common to both the normal host precursor (PrPC)
      and the modified disease form. The availability of these antigenic sites is
      highly restricted by conformational influences resulting in epitope-dependent
      restrictions on antibody binding. Diagnostic immunoassays for TSE have relied
      largely on immunocytochemistry and immunoblotting. Restrictions on epitope
      availability have lead to the formulation by several laboratories of a variety of
      techniques to unmask PrP specific epitopes. In addition, diagnosis requires the
      ability to detect PrPSC specifically in tissue which can also contain immuno
      reactive PrPC. Immuno-detection techniques are discussed relative to their range
      of application, ease of interpretation, specificity and sensitivity.

PMID- 8270105
TI  - The research programme on transmissible spongiform encephalopathies in Britain
      with special reference to bovine spongiform encephalopathy.
AB  - Research into bovine spongiform encephalopathy (BSE) commenced immediately
      following its discovery in November 1986. Formal epidemiological studies
      commenced in June 1987 and were part of a large research programme set up mainly
      at the Central Veterinary Laboratory Weybridge and the Institute for Animal
      Health, AFRC/MRC Neuropathogenesis Unit in Edinburgh. This programme also covered
      the clinicopathology of BSE, transmission studies and molecular chemistry.
      Research results have shown that BSE is a member of the group of diseases known
      as the sub-acute spongiform encephalopathies caused by unconventional
      transmissible agents and which includes scrapie of sheep, from which BSE was
      probably derived, and Creutzfeldt Jakob disease (CJD) of man. The agent causing
      BSE closely resembles strains of the scrapie agent but is not identical.
      Spongiform encephalopathy has developed in sheep, goats, pigs, cattle, marmosets
      and mice but not hamsters following experimental inoculation of brain material
      from confirmed clinical cases of BSE. BSE agent has been detected by mouse bio
      assay in brain from cows from several sources confirmed to have BSE. Infectivity
      has not been detected in spleen, buffy coat, semen, muscles, placenta and bone
      marrow (all following parenteral inoculation) nor in milk/mammary gland, spleen,
      placenta and a variety of lymph nodes following substantial oral exposure. This
      latter route successfully transmitted disease to mice with brain/cerebrospinal
      fluid. The introduction of modified rendering systems, which did not employ
      hydrocarbon solvent extraction, were probably responsible for an increase in
      exposure of cattle from 1981-1988 sufficient to cause the disease. Experiments
      are in progress to investigate the effectiveness of different rendering systems
      used in the European Community and of chemical and physical de-activating
      procedures for destroying BSE and scrapie infectivity. A clear genetic influence
      on disease susceptibility has been suggested but is not yet proven. The
      Agricultural and Food Research Council have set up a large Biology of Spongiform
      Encephalopathies Research Programme to address some of the more fundamental
      unknowns of this group of diseases but it is too early to report results. As with
      scrapie, no epidemiological relationship has been demonstrated between BSE and
      the human diseases through the monitoring programme that has been established by
      the Department of Health to detect such an occurrence. BSE research results so
      far show that controls to protect animal and human health and based initially on
      scrapie research findings, are sound.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270106
TI  - TSE research in Germany: brief statement.

PMID- 8270107
TI  - Prions and nucleic acids: search for "residual" nucleic acids and screening for
      mutations in the PrP-gene.
AB  - Studies on prions involve nucleic acid chemistry under two headings: i) do
      infectious prion particles contain nucleic acids? ii) is it possible by a simple
      procedure to screen the prion protein (PrP)-gene for mutations? The return
      refocusing gel electrophoresis technique was developed to detect by sensitive
      silver staining homogeneous and heterogeneous nucleic acids extracted from highly
      purified scrapie prion preparations. With this method all kinds of nucleic acids
      from a length of 13 nucleotides up to several thousand could be recovered and
      detected with a yield over 90%. Despite extensive nuclease digestion some small
      polynucleotides remained. The results define clear restrictions for a
      hypothetical scrapie-specific nucleic acid. If homogeneous in size, such a
      molecule would be smaller than 80 nucleotides in length at a particle-to
      infectivity ratio near unity; if heterogeneous, scrapie-specific nucleic acids
      would have to include molecules smaller than 240 nucleotides. To detect mutations
      in the PrP-gene, either known mutations from human prion diseases or artificial
      ones in transgenic animals, or to screen for not yet identified mutations in
      patients, a method is required which guarantees detection of mutations which
      might occur in every single position of the whole PrP-ORF. It will be shown that
      a combination of PCR and temperature-gradient gel electrophoresis fulfils these
      requirements. By thermodynamic calculations the shift in the gel electrophoresis
      due to a mutation can be calculated depending on the position of the mutation.
      The theoretical results were tested with the mutations known so far.

PMID- 8270108
TI  - Inactivation of the scrapie agent in a scaled-down procedure for the purification
      of gangliosides from brain tissue.
AB  - The inactivation of the scrapie agent in biologicals was evaluated on a scaled
      down procedure currently in use on a large scale for the purification of
      gangliosides from bovine brain tissue. Residual infectivity was determined by an
      in vivo animal bio-assay using hamsters as the host species and the 263K strain
      as the reference agent. Infectivity was significantly diminished during the early
      stages of purification and infectivity was never detected in the final
      preparations. These results confirmed that a combination of chemicals or physical
      techniques known to affect the viability of the scrapie agent led to complete
      inactivation.

PMID- 8270109
TI  - Gelatine production, the six steps to maximum safety.
AB  - Gelatine production is described in detail, from the slaughterhouse where the raw
      material for gelatine manufacturing is collected, through the processing
      treatment, to the final product which is ready for pharmaceutical or edible
      purposes. The influence of the veterinary inspection of the animal, the batch
      size of the production, the degreasing and acidulation process for bones and the
      different possibilities of the alkaline treatment of hide splits and ossein
      followed by the sterilization steps during the final gelatine manufacturing are
      discussed with regard to the potential destruction of a theoretical BSE
      infection. The question is raised to what extent further activities of the
      gelatine industry seem to be necessary.

PMID- 8270110
TI  - BSE--a risk for man through pharmaceutical products? Position and politics of the
      German pharmaceutical industry.
AB  - Since BSE is not a zoonosis and the occurrence is with some exceptions extremely
      low or absent, the risk to man through pharmaceuticals is remote. However, the
      agent of BSE is very resistant and the disease in cattle is always lethal, as are
      analogous diseases of man. Therefore, the German pharmaceutical industry, through
      a working group, actively contributes to reasonable measurements leading to a
      further reduction of any theoretical risk. This theoretical risk has to be
      evaluated by a balanced consideration of various risk and safety factors. Process
      validation should be reserved for occasional single cases, since it is still time
      consuming and contradicts animal protection. Industry prefers further research
      into the characteristics and behaviour of the BSE agent. The "Note for
      Guidance..." recently established by the EC commission seems a reasonable
      approach for a harmonized attitude of both industry and authorities. The German
      pharmaceutical industry would appreciate a balanced consideration of both
      pharmaceutical and food industries, which would also re-establish the confidence
      of the public.

PMID- 8270111
TI  - Bovine spongiform encephalopathy and its association with the feeding of ruminant
      derived protein.
AB  - The epidemic of bovine spongiform encephalopathy which is currently afflicting
      British cattle probably represents transmission of the sheep disease, scrapie, to
      bovines. Epidemiological evidence suggests that the source of the infection was
      dietary, and implicates commercial cattle rations containing meat and bone meal.
      Although this product is manufactured worldwide from waste animal tissues, only
      sporadic cases of the cattle disease have occurred outside Great Britain where a
      unique combination of factors is considered to be involved; this includes changes
      in manufacturing methods together with the greater use of ovine raw material, an
      increasing proportion of which was probably scrapie-infected. A number of
      legislative measures have been introduced which should lead to the eventual
      elimination of the disease and prevent the occurrence of analogous diseases in
      other species. Meanwhile, pilot-scale spiking studies are underway to determine
      the relative decontamination efficiencies of various procedures used throughout
      the EC to manufacture meat and bone meal; more rigorous methods which are not
      currently employed are also being assessed.

PMID- 8270112
TI  - Transmissible spongiform encephalopathies: virally transmitted amyloidoses.

PMID- 8270113
TI  - The safety of biologicals--old problem, new questions.

PMID- 8270114
TI  - Prion encephalopathies of animals and humans.
AB  - Studies over the past decade of the infectious prions causing scrapie and other
      transmissible neurodegenerative diseases support the hypothesis that these
      pathogens are novel. After convincing evidence was obtained showing that scrapie
      infectivity depends upon a protein component, the term "prion" was introduced to
      distinguish these infectious pathogens from others, including viroids and
      viruses. Enriching fractions from Syrian hamster (SHa) brain for scrapie prion
      infectivity led to the discovery of the prion protein (PrP). Transgenic (Tg) mice
      expressing both SHa and mouse (Mo) PrP genes were used to probe the molecular
      basis of the species barrier and the mechanism of scrapie prion replication.
      Bioassays of brain extracts from two scrapie-infected Tg lines showed that the
      prion inoculum dictates which prions are synthesized de novo, even though the
      cells express both PrP genes. Discovery of mutations in the PrP gene from humans
      with Gerstmann-Straussler-Scheinker disease (GSS), familial Creutzfeldt-Jakob
      disease and fatal familial insomnia established that prion diseases are unique
      among human illnesses--they are both genetic and infectious. Tg mice expressing
      MoPrP with the GSS point mutation spontaneously develop neurologic dysfunction,
      spongiform degeneration and astrocytic gliosis. Inoculation of brain extracts
      prepared from these Tg(GSSMoPrP) mice into Syrian hamsters and Tg mice expressing
      wild-type PrP transgenes has produced neurodegeneration in recipient animals
      after prolonged incubation times. If convincing data on serial passage of prions
      from the inoculated recipients can be obtained, then these results will argue
      that prions are devoid of foreign nucleic acid in accord with many other lines of
      evidence. Although it seems likely that transmissible prions are composed only of
      PrPSc molecules, a hypothetical second component such as a small polynucleotide
      remains a formal possibility. The conversion of PrPc into PrPSc is a post
      translational process that probably occurs in the endocytic pathway. Studies on
      the structure of PrPSc and PrPC have been unsuccessful in defining a post
      translational chemical modification that distinguishes one PrP isoform from the
      other. These findings suggest that the difference between PrPSc and PrPc may be
      conformational. The existence of distinct prion isolates or "strains" with
      different properties poses a conundrum. Distinct isolates produce the
      accumulation of PrPSc in particular sets of CNS neurons. Whether different
      conformers of or Asn-linked CHOs attached to PrPSc are produced in specific
      neurons and are responsible for the properties of distinct prion isolates is
      unknown. The study of prion diseases seems to be emerging as a new area of
      investigation at the interface of such disciplines as genetics, cell biology and
      virology.

PMID- 8270115
TI  - Retroviral spongiform degenerative disease produced by the murine neurotropic
      retrovirus Cas-Br-E.
AB  - The murine neurotropic retrovirus Cas-Br-E causes a non-inflammatory spongiform
      neurodegenerative disease involving the spinal cord, brainstem and cerebellum,
      manifest as a progressive, fatal lower motor neuron disease. Using in utero
      infection of mid-gestation mouse embryos, we have developed a rapid model for the
      study of this disease. Infection of mid-gestation embryos caused paralysis and
      death within 25 days after birth, in contrast to virus-infected neonates, which
      develop disease only after three months. We have found that this model is well
      suited not only to the study of neurovirulence but also to the rapid,
      quantitative assessment of treatment strategies in the CNS. The drug 3'-azido-3'
      deoxythymidine (AZT) was found to cross the placental barrier effectively and
      markedly retarded the onset and course of disease, when given to infected embryos
      through the drinking water of pregnant females. CNS injury seems to be due to a
      direct viral action, but the precise target cells of the virus are uncertain. The
      identification of the viral target cells is complicated by the presence of
      numerous endogenous retroviruses in the mouse genome, as well as difficulties
      with identifying infected cell types by morphology alone. To identify Cas-Br-E
      infected cells precisely, we have performed in situ hybridization studies using a
      Cas-Br-E-specific riboprobe and found that infected cells are in regions of the
      CNS in which spongiform lesions develop and in regions without any obvious
      pathology.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270116
TI  - Molecular biology of prion diseases.

PMID- 8270117
TI  - Pathology of nonhuman spongiform encephalopathies: variations and their
      implications for pathogenesis.
AB  - Microscopic cavitation of the central nervous system (CNS) is a variable, non
      specific feature of several different diseases of animals. In none, however, has
      it received more discussion than in scrapie, a naturally occurring disease of
      sheep, the clinical signs of which have been known for at least two centuries;
      yet consensus on the essential neurodegenerative pathology of scrapie emerged
      only three decades ago. The subsequent recognition of such changes in other
      species, including man, was a crucial factor in establishing the unifying concept
      of the transmissible spongiform encephalopathies (TSE). Recently these disorders
      have been recorded in several additional species, most significantly in domestic
      cattle as a foodborne epidemic. Although the TSE of animals present as
      infections, their pathology is confined to the CNS and has more in common with
      neuronal system degenerations with selective, usually symmetrical and progressive
      lesions, unaccompanied by inflammation. In a given host species the distribution
      of lesions may show variation, as in sheep scrapie or uniformity, as in bovine
      spongiform encephalopathy. Vacuolar or spongiform change is the most useful
      feature in routine diagnosis, in spite of variability in its prominence. The
      molecular pathology of the TSE is characterised by an abnormal isoform of a host
      encoded membrane protein, the prion protein (PrP), accumulation of which is
      specially related to vacuolar change. There remain considerable deficits in our
      knowledge of the pathogenesis of the naturally occurring animal TSE, not least
      the extraneural events leading to CNS involvement and the relative roles of
      vacuolar change and PrP accumulation.

PMID- 8270118
TI  - Neuropathology of human prion diseases (spongiform encephalopathies).
AB  - The human prion diseases (spongiform encephalopathies) comprise Creutzfeldt-Jakob
      disease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and kuru. Their
      clinical characteristics are progressive neurological illness with dementia and
      ataxia as the most prominent signs. The typical neuropathological changes are
      limited to the central nervous system; they consist of spongiform degeneration,
      amyloid plaques, astrocytic gliosis, and nerve cell loss. The aetiology of human
      spongiform encephalopathies remained unclear for many years, until in the 1960s
      they were finally recognized as transmissible diseases similar to scrapie in
      sheep. The infectious agent, termed prion to distinguish it from viruses,
      consists of protein apparently devoid of functional nucleic acid. The finding
      that mutations of the prion protein gene are associated with heritable human
      prion disease has led to wide acceptance of the prion hypothesis. Different
      mutations have been found in prion disease with distinct clinical and
      pathological features in a great number of families. Clinical and
      neuropathological changes not typical of any known variant of human prion disease
      have been shown to be associated with certain mutations of the PrP gene. Further
      findings on the molecular biology and biochemistry of the prion protein will
      probably lead to a new classification of prion diseases.

PMID- 8270119
TI  - Transmission of human spongiform encephalopathies to experimental animals:
      comparison of the chimpanzee and squirrel monkey.
AB  - The agents of kuru and Creutzfeldt-Jakob disease have been consistently
      transmitted from patients with those diseases to chimpanzees and squirrel
      monkeys, as well as to other new-world primates, with average incubation periods
      of two or three years. No other animals have been found so consistently
      susceptible to the agents in human tissues. More rapid and convenient assays for
      the infectious agents would greatly facilitate research on the spongiform
      encephalopathies of humans.

PMID- 8270120
TI  - Infectious cerebral amyloidosis: clinical spectrum, risks and remedies.
AB  - The clinical and pathological features of the NIH series of 209 transmitted cases
      of sporadic Creutzfeldt-Jakob disease (CJD) are compared with familial and
      iatrogenic forms of spongiform encephalopathy. Real or potential risk factors are
      noted, including animal sources such as scrapie and BSE, iatrogenic sources such
      as homografts and cadaveric tissue extracts, and genetic defects in the
      chromosome 20 amyloid precursor gene. The paper concludes with a discussion of
      the means by which such risks may be minimized.

PMID- 8270121
TI  - Experience with milk and an artificial nipple promotes conditioned opioid
      activity in the rat fetus.
AB  - Milk promotes activity in the kappa opioid system of the rat fetus and reduced
      responsiveness in a behavioral bioassay of cutaneous sensitivity. In this study,
      E20 rat fetuses were presented with an artificial nipple (CS) and intraoral
      infusions of milk (US) to condition opioid activity. Paired presentations of the
      CS and US resulted in conditioned changes in perioral cutaneous sensitivity,
      which was not evident in groups exposed to the CS alone, US alone, or explicitly
      unpaired presentations of US and CS. Selective opioid antagonists administered
      between conditioning and testing revealed that reexposure to the nipple resulted
      in activation of the endogenous opioid system. The nipple promoted activity at
      mu, not kappa, opioid receptors. Conditioned opioid activity to an artificial
      nipple in the fetus, which lacks experience with milk or other suckling stimuli,
      implies that conditioned changes in the endogenous opioid system of the newborn
      rat may develop quickly during the first suckling episodes.

PMID- 8270122
TI  - Vocalizations of rhesus (Macaca mulatta) and Japanese (M. fuscata) macaques cross
      fostered between species show evidence of only limited modification.
AB  - Two rhesus and two Japanese macaque infants were cross-fostered between species
      in order to study the effects of auditory experience on vocal development. Both
      the cross-fostered and normally raised control subjects were observed over the
      first 2 years of life and their vocalizations were tape-recorded. We classified
      8053 calls by ear, placed each call in one of six acoustic categories, and
      calculated the rates at which different call-types were used in different social
      contexts. Species differences were found in the use of "coo" and "gruff"
      vocalizations among control subjects. Japanese macaques invariably produced coos
      almost exclusively. In contrast, rhesus macaques produced a mixture of coos and
      gruffs and showed considerable interindividual variation in the relative use of
      one call type or the other. Cross-fostered Japanese macaques adhered to their
      species-typical behavior, rarely using gruffs. Cross-fostered rhesus subjects
      also exhibited species-typical behavior in many contexts, but in some situations
      produced coos and gruffs at rates that were intermediate between those shown by
      normally raised animals of the two species. This outcome suggests that
      environmentally mediated modification of vocal behavior may have occurred, but
      that the resulting changes were quite limited.

PMID- 8270123
TI  - Specific antibody levels in free-ranging rhesus monkeys: relationships to plasma
      hormones, cardiac parameters, and early behavior.
AB  - Levels of tetanus-specific antibodies were assessed in free-ranging, yearling
      rhesus monkeys following prophylactic immunization with tetanus toxoid. Each
      subject's behavior had been observed between 11 and 25 weeks of age and
      approximately 2 months later during its mother's first concentrated mating period
      as a part of another study. Prior to immunization, at approximately 1 year of
      age, cardiovascular parameters, and several plasma parameters [cortisol,
      adrenocorticotrophic hormone (ACTH), growth hormone (GH), interleukin-2 (IL-2),
      and total plasma immunoglobulin G (IgG)] were measured during a brief period of
      captivity. Antibody titers noted approximately 2 weeks after immunization were
      related to cardiovascular parameters. Thus, yearlings with high heart rates and
      low heart rate variability during captivity had the highest tetanus-specific
      serum IgG. Levels of plasma cortisol, ACTH, total IgG, and IL-2 noted at the time
      of capture were unrelated to subsequent antibody levels. Antibody titers were,
      however, positively correlated with GH noted immediately following capture on the
      day prior to immunization. Antibody titers were also related to the infants'
      behavior observed during their mother's first concentrated mating period. Infants
      who were most distressed (high levels of distress vocalization) when their mother
      resumed mating (a time particularly stressful for free-ranging rhesus infants)
      showed lower antibody titers to tetanus immunization as a yearling. The present
      observations add support to the existence of a relationship between behavior
      during exposure to an early stressor and later immune regulation and that certain
      cardiovascular parameters may be related to certain indicators of
      immunoregulation.

PMID- 8270124
TI  - The effects of olfactory experience on nest odor preferences and pup retrieval in
      rats.
AB  - Previous studies have shown that maternal rats are attracted to their own bedding
      and that of other dams but not to that of virgins. The present studies were
      designed to test two hypotheses: First, that the addition of a novel botanical
      odor to the bedding of maternal animals would result in subsequent preferences
      for such an odor. Second, such a preference should enable dams to discriminate
      between pups odorized with familiar and unfamiliar odors as measured by
      differential retrieval of the pups. Both hypotheses were confirmed. In addition,
      we found that preferences established during a first pregnancy and lactation
      affected the retrieval of pups during a second lactational period, but could be
      overturned by new olfactory experience during that second lactational period.

PMID- 8270126
TI  - The impact of renal growth, regression and regrowth in experimental diabetes
      mellitus on number and size of proximal and distal tubular cells in the rat
      kidney.
AB  - Diabetic renal growth, regression and regrowth was studied using stereological
      methods on perfusion-fixed rat kidneys. The study lasted 13 weeks and comprised
      one control group and three diabetic groups. The first diabetic group was
      hyperglycaemic for 13 weeks. The second group was hyperglycaemic for 10 weeks and
      then normoglycaemic for 3 weeks. The third group was similar to the second group
      except that during the last week the animals were again hyperglycaemic. Using an
      optical dissector on the plastic-embedded kidney slices, the number and size of
      proximal and distal tubular cells were estimated. The number of proximal and
      distal tubular cells increased by 37% and 36% during 13 weeks of experimental
      diabetes and the mean volume of the proximal tubular cells increased by 12%
      whereas the 16% increase in mean tubular cell volume was only borderline
      significant as compared to the control group. Normoglycaemia for 3 weeks
      normalized the mean volume of distal tubular cells but the proximal tubular cells
      tended to be 7% smaller than those in control rats. The number of proximal cells
      remained increased by 21% compared with the control rats and the number of distal
      tubular cells retained a 17% insignificant increase. After regrowth the volume of
      proximal tubular cells was 20% greater than in the second diabetic group and the
      other parameters were unchanged. In conclusion, 13 weeks of experimental diabetes
      induced formation of 36% more tubular cells that were enlarged only by about 14%.
      Normoglycaemia for 3 weeks failed to normalize the cell number. Repeated
      hyperglycaemia for 1 week after 2 weeks of normoglycaemia increased the size of
      the proximal tubular cells.

PMID- 8270125
TI  - Coagulation activation in diabetes mellitus: the role of hyperglycaemia and
      therapeutic prospects.
AB  - Numerous studies have shown that coagulation abnormalities occur in the course of
      diabetes mellitus, resulting in a state of thrombophilia. These observations are
      supported by epidemiological studies which demonstrate that thromboembolic events
      are more likely to occur in diabetic patients. The coagulation abnormalities
      observed in diabetic patients seem to be caused by the hyperglycaemia, which also
      constitutes the distinguishing feature of this disease. These data are also
      supported by in vitro studies which demonstrate how glucose can directly
      determine alterations in the coagulation system. The abnormalities observed
      involve all stages of coagulation, affecting both thrombus formation and its
      inhibition, fibrinolysis, platelet and endothelial function. The final result is
      an imbalance between thrombus formation and dissolution, favouring the former.
      Hyperglycaemia probably determines the onset of these abnormalities through three
      mechanisms which are, respectively, non-enzymatic glycation, the development of
      increased oxidative stress and a decrease in the levels of heparan sulphate. The
      first seems to affect the functionality of key molecules of coagulation in a
      negative sense. Oxidative stress constitutes an important pro-thrombotic
      stimulus, while the decrease in heparan sulphate determines a reduction in
      antithrombotic defenses. Good metabolic control could play a key role in
      controlling the coagulation irregularities in diabetes. However, considering the
      difficulties in achieving such an objective, it is possible that the use of drugs
      may represent a valid alternative. In fact, several drugs exist which are of
      potential interest. It is, however, necessary to perform long-term studies which
      demonstrate unequivocably that by controlling the coagulation abnormalities in
      diabetic patients, prolongation of life is possible.

PMID- 8270127
TI  - Contrasting effects of treatment with omega-3 and omega-6 essential fatty acids
      on peripheral nerve function and capillarization in streptozotocin-diabetic rats.
AB  - Essential fatty acid metabolism is impaired by diabetes mellitus and this may be
      important in the aetiology of peripheral nerve dysfunction. The effects of gamma
      linolenic acid (omega-6) and fish oil (omega-3) alone, and in combination, on
      nerve function and capillarization were examined in 2-month streptozotocin
      diabetic rats. Diabetes resulted in approximately 15% and 23% decreases in
      saphenous sensory and sciatic motor nerve conduction velocities, respectively (p
      < 0.001). Motor and sensory conduction velocities were in the non-diabetic range
      after both preventive and reversal omega-6 treatment of diabetic rats (p <
      0.001). No significant changes occurred in omega-6 treated non-diabetic rats.
      Preventive omega-3 treatment was largely ineffective. Reversal treatment with a
      combination of omega-6 and omega-3 fatty acids was marginally effective and
      improved motor (p < 0.05), but not sensory conduction velocity. In vitro
      measurement of sciatic nerve resistance to hypoxic conduction failure in diabetic
      rats revealed a 56% increase in the time taken for the compound action potential
      amplitude to be reduced by 80% (p < 0.01) compared to non-diabetic rats. This was
      partially prevented by omega-6 treatment (29% increase, p < 0.01). Reversal omega
      6 treatment had a lesser effect (37% increase, p < 0.05 compared to untreated
      diabetic rats). omega-3 treatment had no significant effect on conduction failure
      time. Sciatic endoneurial capillary density increased by 11% with preventive
      omega-6 treatment (p < 0.05), but was unaffected by reversal omega-6 and by omega
      3 treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270128
TI  - Pancreatic beta cell line MIN6 exhibits characteristics of glucose metabolism and
      glucose-stimulated insulin secretion similar to those of normal islets.
AB  - Glucose-stimulated insulin secretion, glucose transport, glucose phosphorylation
      and glucose utilization have been characterized in the insulinoma cell line MIN6,
      which is derived from a transgenic mouse expressing the large T-antigen of SV40
      in pancreatic beta cells. Glucose-stimulated insulin secretion occurred
      progressively from 5 mmol/l glucose, reached the maximal level approximately
      seven-fold above the basal level at 25 mmol/l, and remained at this level up to
      50 mmol/l. Glucose transport was very rapid with the half-maximal uptake of 3-O
      methyl-D-glucose being reached within 15 s at 22 degrees C. Glucose
      phosphorylating activity in the cell homogenate was due mainly to glucokinase;
      the Vmax value of glucokinase activity was estimated to be 255 +/- 37 nmol.h-1.mg
      protein-1, constituting approximately 80% of total phosphorylating activity,
      whereas hexokinase activity constituted less than 20%. MIN6 cells exhibited
      mainly the high Km component of glucose utilization with a Vmax of 289 +/- 18
      nmol.h-1.mg protein-1. Thus, glucose utilization quantitatively and qualitatively
      reflected glucose phosphorylation in MIN6 cells. In contrast, MIN7 cells, which
      exhibited only a small increase in insulin secretion in response to glucose, had
      4.7-fold greater hexokinase activity than MIN6 cells with a comparable activity
      of glucokinase. These characteristics of MIN6 cells are very similar to those of
      isolated islets, indicating that this cell line is an appropriate model for
      studying the mechanism of glucose-stimulated insulin secretion in pancreatic beta
      cells.

PMID- 8270129
TI  - Quantitative phenotypic and functional analyses of islet immune cells before and
      after diabetes onset in the BB rat.
AB  - Inflammatory cells invading islets are thought to be mediators of islet
      destruction in spontaneous autoimmune diabetes mellitus. Thus methods were
      developed to isolate and characterize in situ islet inflammatory cells from 75-95
      day-old prediabetic and diabetic BB rats. Islet inflammatory cells were
      structurally examined using single- and double-colour flow cytometry. Functional
      studies consisted of cytolytic assays using normal rat islet target cells and in
      situ islet or spleen effector cells. Structural data reveal natural killer cells
      to be the major cell population (70%) of total immune cells present in inflamed
      islets during prediabetes. At diabetes onset, the natural killer cell population
      remained at a high level (47%), but an increasing population of T cells (40%) was
      noted also. Analyses of T-cell subsets before and after diabetes onset revealed
      CD4+ T cells as predominant (50-55% of total T cells) with double-negative (CD4
      CD8-) T cells (25-30%) and CD8+ T cells (15-20%) also present in significant
      quantities. Activated T cells accounted only for a minority of T cells (< 3%).
      Functional studies indicate that in situ islet-derived cytolytic effector cells
      are more potent killers (ten-fold) of normal islet target cells than are splenic
      effector cells. These data suggest that in situ islet inflammatory cells (a) can
      be quantitatively studied both structurally and functionally; (b) express
      structural phenotypes differing substantially from splenic mononuclear cell
      populations; (c) are considerably more cytolytic than splenic effectors; and (d)
      should prove informative in determining the most significant autoimmune
      functional events prior to and during islet beta-cell destruction.

PMID- 8270130
TI  - Insulin autoantibodies and high titre islet cell antibodies are preferentially
      associated with the HLA DQA1*0301-DQB1*0302 haplotype at clinical type 1 (insulin
      dependent) diabetes mellitus before age 10 years, but not at onset between age 10
      and 40 years. The Belgian Diabetes Registry.
AB  - Demographic and biological data were collected from all Caucasian Type 1 diabetic
      patients (n = 279) who were recruited at clinical onset by the Belgian Diabetes
      Registry over 34 months. The male/female ratio was significantly higher for onset
      between age 20 and 40 years (2.4) than before age 20 years (1.0); no age-or sex
      differences were noticed in serum fructosamine concentration. Total and high
      concentrations of insulin autoantibodies and islet cell antibodies were
      preferentially associated with the HLA DQA1*0301-DQB1*0302 susceptibility
      haplotype. The occurrence of both types of antibodies was also correlated,
      irrespective of haplotype. At onset before age 10 years, the high risk genotype
      DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 was more prevalent than all other DQA1
      DQB1 genotypes taken together, leading to a higher prevalence of the DQA1*0301
      DQB1*0302 haplotype in this age group (75%) than in the 10-39 years age group
      (54%). Under age 10 years, the presence of DQA1*0301-DQB1*0302 was strongly
      associated with insulin autoantibodies (90%) and islet cell autoantibodies (92%
      with 85% of high titre), whereas patients without this haplotype were less
      frequently positive for insulin autoantibodies (31%) or islet cell autoantibodies
      (38% high titre). In the group with onset at age 10-39 years, the DQA1*0301
      DQB1*0302 haplotype presented a lower association with insulin autoantibodies
      (approximately 40%) and islet cell autoantibodies (50 to 65% high titre),
      prevalences which no longer differed from those in subjects lacking this
      haplotype.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270131
TI  - Insulin receptor tyrosine kinase activity is reduced in monocytes from non-obese
      normoglycaemic insulin-resistant subjects.
AB  - Insulin sensitivity has been quantified by i.v. insulin tolerance test (0.1 U/kg
      of body weight) in 18 (11 male/7 female) non-obese (body mass index range 19-25
      kg/m2) normoglycaemic subjects. We then compared the tyrosine kinase activity and
      internalization of insulin receptor in monocytes from the six most insulin
      sensitive (group 1) and the six most insulin-resistant (group 3) subjects.
      Tyrosine kinase activity was measured on immunopurified receptors using 32P-ATP
      and poly-glutamic acid 4: tyrosine 1, sodium salt (poly-glu-tyr 4:1). Insulin
      internalization was studied by incubating cells with 1 nmol/l 125I-insulin and
      measuring total cell-bound and intracellular 125I-insulin by an acid dissociation
      procedure. Basal (in the absence of insulin) receptor kinase activity was similar
      in both groups. Maximal (in the presence of 100 nmol/l insulin) kinase activity
      was 41% lower in group 3 (13.8 +/- 3.6 fmoles 32P-ATP incorporated vs 23.3 +/-
      4.0, p = 0.1). Delta increment of receptor kinase activity after insulin
      stimulation (calculated by subtracting basal from maximal activity) was
      significantly (p < 0.05) reduced in group 3 (21.3 +/- 3.8 vs 11.1 +/- 2.1) and
      significantly (p < 0.05) correlated to the in vivo insulin sensitivity. Both
      total cell-bound (0.70 +/- 0.09% of total radioactivity added vs 0.83 +/- 0.15)
      and intracellular (0.39 +/- 0.05 vs 0.44 +/- 0.09) 125I-insulin were similar in
      the two groups. These data suggest that in non-obese, normoglycaemic subjects a
      defective insulin receptor tyrosine kinase activity may contribute to the
      development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270132
TI  - An in-frame insertion in exon 3 and a nonsense mutation in exon 2 of the insulin
      receptor gene associated with severe insulin resistance in a patient with Rabson
      Mendenhall syndrome.
AB  - We have studied the structure and function of the insulin receptor in a patient
      (PK) with severe insulin resistance and Rabson-Mendenhall syndrome. Insulin
      binding to cultured fibroblasts from PK was almost not detectable and insulin
      induced insulin receptor autophosphorylation and glucose uptake was abolished.
      The structure of the receptor gene was analysed by sequencing amplified products
      of the 22 exons with the flanking intron regions directly as well as after
      subcloning in pUCBM20 plasmids. Two mutant alleles of the insulin receptor gene
      were detected. One allele contains in-frame 12 additional base pairs in exon 3
      coding for the amino acids Leu-His-Leu-Val located between Asp-261 and Leu-262 in
      the receptor's extracellular domain, being the first report of an insertion
      mutation of the insulin receptor gene. In the other allele Arg-86 in exon 2 is
      changed into a stop codon. Therefore, PK is compound heterozygous at the insulin
      receptor locus. Direct cDNA sequencing indicates that both mutant alleles are
      expressed in the patient's fibroblasts. Studies of the parents' fibroblasts
      revealed that PK inherited the insertion mutation from the father and the
      nonsense mutation from the mother. Insulin binding to fibroblasts of the mother
      was reduced (63% of control cells) and hormone binding to the father's cells
      shows a larger reduction (37% of control cells), but less severe than the
      patient's cells (11% of control). This investigation provides further evidence
      that the Rabson-Mendenhall syndrome is causally related to mutations in the
      insulin receptor gene.

PMID- 8270133
TI  - Ten-year cardiovascular mortality in relation to risk factors and abnormalities
      in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non
      diabetic subjects.
AB  - The purpose of the present study was to examine 10-year cardiovascular morbidity
      and mortality in patients with newly-diagnosed Type 2 (non-insulin-dependent)
      diabetes mellitus and non-diabetic control subjects and to evaluate the effects
      of general risk factors, plasma insulin, urinary albumin excretion, lipoprotein
      abnormalities characteristic of Type 2 diabetes and the degree of hyperglycaemia
      in diabetic patients on cardiovascular mortality. Furthermore, the extent to
      which the above-mentioned factors could contribute to the excessive
      cardiovascular mortality observed in diabetic patients was examined. In the years
      1979-1981, altogether 133 (70 men, 63 women) newly-diagnosed patients with Type 2
      diabetes and 144 (62 men, 82 women) non-diabetic control subjects aged 45-64
      years were studied. Both groups were re-examined in the years 1985-1986 and 1991
      1992. The impact of different factors on cardiovascular mortality was examined by
      univariate analyses after adjustment for age and sex and by multiple logistic
      regression analyses. The age-standardized total and cardiovascular mortality
      rates were substantially higher in diabetic men (17.8 and 15.0%, total and
      cardiovascular mortality, respectively p = 0.06 and NS) and women (18.5 and
      16.6%, p < 0.01 for both) than in non-diabetic control men (5.2% both total and
      cardiovascular mortality) and women (4.2 and 2.2%). Cardiovascular mortality was
      not related to the treatment modality (diet, oral drugs, insulin) at 5 years from
      diagnosis. Use of diuretics, beta-blocking agents or their combination at
      baseline did not make a significant contribution to cardiovascular mortality
      either. In multiple logistic regression analysis on diabetic patients, age, LDL
      triglycerides, smoking, blood glucose and ischaemic ECG at baseline had
      independent associations with cardiovascular mortality. Interestingly, urinary
      albumin excretion rate measured at 5-year examination also predicted 10-year
      cardiovascular mortality after adjustment for the effects of major risk factors
      including lipoprotein abnormalities, but its predictive power reduced to a
      nonsignificant level when the effect of plasma glucose was taken into account.
      The relative risk of cardiovascular mortality associated with diabetes was 8.2
      after allowing for age alone, but it declined to 3.7 when all contributing
      factors from the baseline examination (except blood glucose) were taken into
      account. In conclusion, the present results indicate that LDL triglycerides
      and/or other changes in lipoprotein composition characteristic of Type 2 diabetes
      and manifesting as elevated serum triglycerides are atherogenic and they strongly
      predict increased cardiovascular mortality.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270134
TI  - Hepatic glucose production during intraperitoneal and intravenous closed-loop
      insulin regulation of blood glucose in type 1 (insulin-dependent) diabetic
      patients.
AB  - Intraperitoneal infusion of insulin should be more physiological than intravenous
      insulin since part of the insulin is directed toward the portal vein, which
      allows the liver to retain its major role in glucose homeostasis. The regulation
      of hepatic glucose production during the intraperitoneal and intravenous
      infusions of insulin were compared in eight Type 1 (insulin-dependent), C-peptide
      deficient diabetic patients. Primed, continuous infusions of [6,6-2H]glucose were
      given in the postabsorptive state and during continuous infusion of unlabelled
      glucose at 1.5 and 4 mg/kg.min, while normoglycaemia was maintained by closed
      loop intraperitoneal and intravenous insulin delivery. During all three periods,
      plasma glucose concentrations remained near normal (variations 3.8-6.1%). The
      insulin infusion rates required for normal plasma glucose concentrations were
      essentially the same for the intravenous and intraperitoneal routes in all cases,
      although the variations were greater with intraperitoneal insulin. Plasma free
      insulin levels were only slightly, non-significantly lower with intraperitoneal
      infusion than with intravenous infusion. Hepatic glucose production was
      significantly lower with intraperitoneal insulin during all three conditions:
      basal: 1.71 +/- 0.14, i.p. vs 2.37 +/- 0.26 mg/kg.min, i.v.; 1.5 mg/kg.min
      glucose infusion: 0.49 +/- 0.23, i.p. vs 0.88 +/- 0.18 mg/kg.min, i.v.; 4
      mg/kg.min glucose infusion: 0.31 +/- 0.10, i.p. vs 0.56 +/- 0.12 mg/kg.min, i.v..
      These results, obtained with steady-state conditions for plasma glucose, isotopic
      plasma glucose enrichments and unlabelled glucose infusion rates, suggest that
      better control of hepatic glucose production leading to normoglycaemia was
      achieved with the intraperitoneal infusion.

PMID- 8270135
TI  - Post-hypoglycaemic hyperketonaemia does not contribute to brain metabolism during
      insulin-induced hypoglycaemia in humans.
AB  - It is controversial as to whether ketone bodies are utilized by the human brain
      as a fuel alternative to glucose during hypoglycaemia. To clarify the issue, we
      studied 10 normal volunteers during an experimental hypoglycaemia closely
      mimicking the clinical hypoglycaemia of patients with Type 1 (insulin-dependent)
      diabetes mellitus or insulinoma. Hypoglycaemia was induced by a continuous
      infusion of insulin (0.40 mU.kg-1.min-1 for 8 h, plasma insulin approximately 180
      pmol/l) which decreased the plasma glucose concentration to approximately 3.1
      mmol/l during the last 3 h of the studies. Subjects were studied on two
      occasions, i.e. spontaneous, counterregulatory-induced post-hypoglycaemic
      increase in 3-beta-hydroxybutyrate (from approximately 0.2 to approximately 1.1
      mmol/l at 8 h), or prevention of post-hypoglycaemic hyperketonaemia (plasma beta
      hydroxybutyrate approximately 0.1 mmol/l throughout the study) after
      administration of acipimox, a potent inhibitor of lipolysis. In the latter study,
      glucose was infused to match the hypoglycaemia observed in the former study. The
      glycaemic thresholds and overall responses of counterregulatory hormones,
      symptoms (both autonomic and neuroglycopenic), and deterioration of cognitive
      function (psychomotor tests) were superimposable in the control study in which
      ketones increased spontaneously after onset of hypoglycaemic counterregulation,
      as compared to the study in which ketones were suppressed (p = NS). The fact that
      responses of counterregulatory hormones, symptoms and deterioration in cognitive
      function were not exaggerated when posthypoglycaemic hyperketonaemia was
      prevented, indicate that during hypoglycaemia, the counterregulatory-induced
      endogenous hyperketonaemia does not provide the human brain with an alternative
      substrate to glucose. Thus, it is concluded that during hypoglycaemia, endogenous
      hyperketonaemia does not contribute to brain metabolism and function.

PMID- 8270136
TI  - Prevalence of type 2 (non-insulin-dependent) diabetes mellitus and impaired
      glucose tolerance in the Japanese general population: the Hisayama Study.
AB  - We determined the population-based prevalence of diabetes mellitus in members of
      the Japanese community, Hisayama aged 40-79 years old by a 75-g oral glucose
      tolerance test. The basic population used to calculate diabetic prevalence was
      1,077 men (72.8% of the whole population in the same age range) and 1,413 women
      (80.8%) including ten diabetic patients on insulin therapy. In addition, we
      compared the prevalence of history of diabetes which was acquired by interview or
      questionnaire, between participants and non-participants in the 75-g oral glucose
      tolerance test, but they were not statistically different. The age-adjusted
      prevalence of diabetes to world population was 12.7% for men and 8.4% for women,
      and that of impaired glucose tolerance was 19.6% for men and 18.4% for women.
      These figures were much higher than those previously reported from several
      Japanese communities. The results obtained from the present study could reveal
      true prevalence of diabetes among the Japanese population. In addition, the
      reasons for the increasing prevalence of diabetes among the recent Japanese
      population are also discussed.

PMID- 8270137
TI  - Inhibition of the high-affinity glucose transporter GLUT 1 affects the
      sensitivity to glucose in a hamster-derived pancreatic beta cell line (HIT).
AB  - HIT is a hamster-derived beta-cell line which in contrast to normal beta cells
      that only express the high Km GLUT-2 glucose transporter, also expresses the low
      Km glucose transporter GLUT 1. In HIT cells the abnormal glucose transport
      mechanism is associated with a marked shift to the left of the glucose-induced
      insulin release dose-response curve. We have used this cell model to investigate
      whether changes in glucose transport affect the glucose-induced insulin release.
      HIT cells were first incubated with a concentration of cytochalasin B (0.4
      mumol/l) that selectively inhibits the GLUT-1 but not the GLUT-2 transporter. The
      consequences of blocking glucose phosphorylation and insulin release were
      studied. Exposure to 0.4 mumol/l cytochalasin B for 1 h caused a selective loss
      of the low Km transport: the calculated Vmax of GLUT 1 was reduced from 1726 +/-
      98 to 184 +/- 14 pmol.mg protein-1 5 min-1 (mean +/- SEM, n = 6, p < 0.005),
      while no major difference in the high Km (GLUT-2) transport was observed. In
      cytochalasin B exposed HIT cells the glucose phosphorylating activity (due to
      hexokinase and glucokinase) was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270138
TI  - The selection of control subjects for case/control analysis of susceptibility to
      type 1 (insulin-dependent) diabetes mellitus.

PMID- 8270139
TI  - Susceptibility to type 1 (insulin-dependent) diabetes mellitus is determined by
      MHC class II molecules. What about DR4?

PMID- 8270140
TI  - The role of anti-oxidative treatment in diabetes mellitus. This meeting was held
      in Frankfurt am Main, Germany.

PMID- 8270141
TI  - MHC class II molecules and the immune response to the ABBOS peptide of bovine
      serum albumin: prelude to type 1 (insulin-dependent) diabetes?

PMID- 8270142
TI  - Evolution of the glucokinase glucose sensor paradigm for pancreatic beta cells.

PMID- 8270143
TI  - The effects of corticosteroid hormones and thyroid hormones on lymphocyte
      viability and proliferation during development and metamorphosis of Xenopus
      laevis.
AB  - Metamorphosis in the South African clawed frog, Xenopus laevis, is characterized
      by a striking loss of lymphocytes in the thymus, liver, and spleen. Changes in
      the proliferative responses of splenocytes and thymocytes to T cell mitogens and
      semi-allogeneic cells are also observed at metamorphosis. Because the levels of
      circulating thyroid hormones (TH) and corticosteroid hormones (CH) increase
      dramatically during the climax of metamorphosis, we have investigated the
      possible role of TH and CH as mediators of the changes in lymphocyte numbers or
      lymphocyte function. Here we report on the in vitro effects of CH and TH on
      lymphocyte viability and on phytohemagglutinin-P (PHA)-stimulated lymphocyte
      proliferation at prometamorphosis and climax of metamorphosis. We have observed
      consistently significant inhibition of proliferation by corticosterone. In
      contrast, we have observed inconsistent inhibition of proliferation by both
      thyroxine (T4) and triiodothyronine (T3). In short-term studies, the viability of
      thymocytes and splenocytes was reduced in the presence of CH but not TH. These
      observations are consistent with a hypothesis that loss of larval lymphocytes and
      changes of lymphocyte function at metamorphosis may be due to elevated
      concentrations of CH rather than TH. Because CH have been shown to enhance TH
      induced effects during metamorphosis, we looked at the combined effects of these
      agents on PHA-stimulated lymphocyte proliferation. While each agent was
      inhibitory in several experiments, there was no significantly greater inhibition
      when splenic lymphocytes were cultured with both.

PMID- 8270144
TI  - Patterns of nerve growth factor (NGF), proNGF, and p75 NGF receptor expression in
      the rat incisor: comparison with expression in the molar.
AB  - Nerve growth factor (NGF), a target-derived neurotrophic substance, may have
      broader biological functions in various types of non-neuronal differentiating
      cells. The effects of NGF are dependent on initial binding of NGF to specific
      cell-surface receptors (p75NGFR and p140prototrk) on responsive cells. The
      continuously growing rat incisor offers an excellent model demonstrating defined
      territories of differentiation of specific cell populations. We used
      immunohistochemistry to determine sites of NGF, proNGF and p75NGFR accumulation
      in the rat incisor, whereas NGF mRNA expression was visualized by in situ
      hybridization in the developing rat molar and incisor. Strictly similar patterns
      of NGF mRNA, proNGF and NGF expression were observed in differentiating cells
      responsible for the production of the main structural matrices of the tooth.
      Thus, proNGF-like and NGF-like immunoreactivity, as well as the NGF mRNA signal
      were observed in preameloblasts and young ameloblasts of the dental epithelium
      and in polarizing odontoblasts of the dental mesenchyme. In contrast, the
      distribution of p75NGFR was correlated with differentiation event only in dental
      mesenchyme: polarizing odontoblasts expressed p75NGFR whereas the molecule was
      absent in functional odontoblasts. In dental epithelium, the restricted
      expression of p75NGFR in ameloblast precursor cells was correlated with
      proliferative phenomena. The patterns of proNGF, NGF and p75NGFR expression in
      epithelium and mesenchyme implicate both an autocrine and paracrine mode of
      action of the NGF molecule in dental tissues. The findings reported here are
      important for understanding NGF action in specific dental cell populations and
      suggest that this molecule is involved in the cascade of events that directs
      tooth development.

PMID- 8270145
TI  - Transfection of metastatic capability with total genomic DNA from human and mouse
      metastatic tumour cell lines.
AB  - From a large series of experiments involving transfer of high molecular weight
      total genomic DNA from highly metastatic human and mouse tumour cell lines to
      other mouse tumour cell lines we have derived a few cell lines with greatly
      augmented metastatic properties. In one of these experiments the transfected cell
      line (designated AH8 Test) not only colonised the lungs but also formed secondary
      tumour colonies in several extrapulmonary sites including the skin, skeletal
      muscles, bone, liver diaphragm, spleen and heart. There were no qualitative and
      quantitative effects of this magnitude when we used DNA from several non
      metastatic or non-tumourigenic sources. Secondary transfection of metastatic
      capability with DNA obtained from a metastasis formed by one of the primary
      transfectant lines (AH8 Test) has also been accomplished. Concomitant transfer of
      human DNA through both transfection cycles in this experiment was confirmed by a
      variety of methods including Southern blot analysis, in situ hybridisation and
      polymerase chain reaction (PCR) amplification of DNA using primers recognising
      human-specific Alu repeat sequences. The findings offer opportunities for the
      isolation of sequences programming metastatic behaviour and we have cloned and
      sequenced a fragment of human DNA, which has not been previously characterised,
      from the transfected cells.

PMID- 8270146
TI  - [Do sex steroids cause breast and genital cancers? Epidemiologic data--the
      current status (July 1993)].
AB  - Present literature on epidemiology shows, that estrogens administered either in
      the form of contraceptives or as replacement therapy will reduce the relative
      risk of ovarian carcinoma to less than 0.5. Likewise this result was also seen in
      all studies without exception. The reduction becomes manifest after four months
      and is maintained for many years following discontinuation. The same applies to
      corpus carcinoma, provided estrogens are administered concomitantly with
      gestagens. Administration of estrogens alone results in enhancing the relative
      risk up to 3-4. Hyperproliferation can lead to carcinoma of the endometrium. No
      data are presently available for cervical carcinoma, that would justify the
      assumption, that the relative risk for squamous cell carcinoma of the cervix is
      increased. This statement does not apply to the adenocarcinoma of the cervix,
      since too few cases have been studied. The following statements apply to
      carcinoma of the breast: OC's (oral contraceptives) taken before the age of 45 do
      not increase the relative risk. This is also true of females, for whom a risk
      factor exists, as for example family case history, period of administration,
      benign diseases of the breast, use of OC's before the first pregnancy,
      nulliparity, no breast-feeding. Possible, but not proven is a slight increase in
      relative risk to 1.3 in females, in whom carcinoma of the breast had been
      diagnosed before the age of 34. If this increase is accepted, one must likewise
      expect a decrease in relative risk after the age of 45. A hormonal replacement
      therapy for up to four years will not increase the relative risk. This applies
      also to replacement therapy with gestagens, even though only few data are
      available at present. It has been concluded from the results of some studies,
      that a slight increase in relative risk to 1.3 is possible after long-term
      therapy (more than 15 years). However, no causal relationship to cancer of the
      breast has been established. It has not been claimed so far, that estrogens cause
      cancer of the breast. Should the slight relative risk increase be confirmed, this
      would mean, that in a small group of very young females, estrogens may promote
      the growth of an already existing cancer of the breast.

PMID- 8270147
TI  - [Obstetric data processing with a personal computer].
AB  - Update computer technology is an increasingly useful tool in medicine for more
      accurate documentation, avoidance of multiple documentation, improvement of
      service performance, quicker and easier data processing and evaluation and hence
      quality assurance. We developed an obstetric data recording programme for an IBM
      compatible personal computer according to the MS-DOS command programme. A laser
      printer with dual paper feed is available. The relational database system Clipper
      is used for programming. The programme comprises at present 179 data fields and
      is subdivided on the input side into: data on anamnesis and partus, course of
      puerperium, infant data. This gives the print-outs: birth protocol, adhesive
      labels for the temperature curves of the mother and of the infant, respectively,
      birth record book and mother-infant health passport, furthermore, list print
      outs: infant record book, transferred/decreased infants, birth lists relating to
      midwives, and, in addition, physician's report on the mother and the child, and
      finally, automated monthly and annual statistics. From August 1990 to July 1992,
      all events were stored by the computer, so that a total of 5,572 data items have
      been recorded to date. The primary scope of recording was 98.4% already in the
      first year of full operation of the database. Computer feed-in was affected
      directly after each data item became available. Application is fully integrated
      into normal clinical everyday work. To ensure best possible motivation and
      acceptance, special attention was paid to user friendliness and immediate print
      outs whenever required. Attention was also given to the inclusion of infant
      follow-up data. The computer programme has been accepted for daily operation, and
      the necessary data quality has been attained by means of proper choice of the
      appropriate user groups and manifold measures to ensure integration, safe
      working, continual servicing and creation of suitable working and data feed
      conditions.

PMID- 8270148
TI  - [Syphilis screening in pregnancy].
AB  - A review of the effectiveness of antenatal screening for syphilis in the 3 year
      period 1989 to 1991 was made at the Department of Obstetrics, University of
      Zurich. In a total of 5640 pregnancies, 30 had a reactive TPHA-result. Using FTA
      ABS-test and IgM-tests, 2 were false positive and 27 were considered as
      seropositive without signs of infection. Only one patient had a serology
      consistent with a latent syphilis. In Switzerland, every year approx. 9 newborns
      with positive serology for syphilis are found. Most of them, however, are not
      infected and the result only reflects the serostatus of the mother. Because of
      these poor results we doubt the usefulness of an antenatal screening programme
      for syphilis.

PMID- 8270149
TI  - [Condylomata acuminata in pregnancy. Is there an indication for Cesarean
      section?].
AB  - Condylomata acuminata are very rare in children, although the prevalence of
      clinically or cytologically visible human papilloma virus infections is high. We
      report on a 28-year old G IV, P II with genital warts at the time of delivery,
      who had a baby boy without any signs of HPV-infection. The condylomata of the
      mother persisted, and subsequently laser vaporisation was performed one year
      after delivery. One year after laser therapy, a recurrent HPV-infection in the
      mother was detected. At this time, her two year old son had condylomata on his
      scrotum. The same serotypes, HPV 6 and 11, could be identified in the mother and
      child. With this case report, we discuss the possible ways of transmission and
      consequent clinical management of HPV infections in pregnancy.

PMID- 8270150
TI  - [Detection or exclusion of fetal trisomy 18 by in-situ-hybridization of the
      histologic section].
AB  - In-situ-hybridization using a chromosome-specific centromeric DNA probe on
      paraffin embedded tissue of placental and foetal origin allows the detection of
      numerical chromosome anomalies, even after several years. This may facilitate the
      diagnosis of late abortions in those cases in which a conventional cytogenetic
      examination was not performed, but the clinical picture suggests a chromosomal
      syndrome. We demonstrate chromosome DNA fluorescence in-situ-hybridisation (FISH)
      with a chromosome 18 specific (peri) centromeric repeat probe, on paraffin
      sections of one case with a cytogenetically proven and of three cases with a
      questionable Edwards-syndrome, thus confirming or excluding trisomy 18 in two of
      the cases.

PMID- 8270151
TI  - [Acute effects of cigarette smoking on fetal cardiovascular and uterine Doppler
      parameters].
AB  - The purpose of this study was to assess the effects of smoking one cigarette
      (nicotine mean 0.63 +/- 0.17 mg) on uterine- and foetal cardiovascular Doppler
      parameters in healthy pregnant smokers. All pregnancies (n = 16; mean gestational
      age: 36 +/- 4 weeks) had been uneventful and all foetuses were appropriate for
      gestational age with normal baseline Doppler parameters and normal foetal outcome
      (birthweight: 3254 +/- 340 grams). Measurements, performed immediately before and
      after smoking, included pulsatility index (PI) of umbilical artery (UA), middle
      cerebral artery (MCA), foetal descending aorta and uterine artery as well as
      maternal and foetal heart rate. The ratio of UA/MCA PI was used to assess
      centralisation. Changes in foetal cardiac output were determined by: time
      velocity integral times heart rate, at aortic and pulmonary valve level. Foetal
      heart rate (p < 0.0005, paired t-test) and maternal heart rate (p < 0.05)
      increased significantly. All other parameters did not change significantly.
      However, in one additional woman with labile hypertension and increased baseline
      uterine artery PI (1.9), smoking of one cigarette caused a substantial rise in
      uterine artery PI to 3.25 ten minutes after smoking. Middle cerebral artery PI
      decreased from 2.2 to 1.18 with an unchanged cardiac output and umbilical artery
      PI raising the UA/MCA PI ratio from 0.51 to 0.81, suggesting a brain sparing
      effect. Smoking of one cigarette raised maternal and foetal heart rate. There was
      no evidence of other cardiovascular effects or centralisation in healthy foetuses
      of normal pregnancies, but this might not be true in foetus of pathologic
      pregnancies.

PMID- 8270152
TI  - [Pelviscopic treatment of female sterility].
AB  - In 1988 and 1989 176 patients underwent pelviscopy at the Kiel University
      Hospital of Gynaecology for primary or secondary sterility of at least 12 months
      duration. 120 patients (68%) filled in a questionnaire on the therapeutic results
      after 2 to 3 years. Following peripheral salpingostomy in 18 patient, an
      intrauterine pregnancy developed in 22% of these cases, while an ectopic
      pregnancy occurred in 11% of the cases. After fimbrioplasty in 37 cases, the
      intrauterine pregnancy rate amounted to 43%, whereas the rate was 50% following
      salpingoovariolysis. 4 patients with a subserous or intramural myoma, measuring
      2.5 to 8 cm in diameter, but no other pathological signs of disturbed fertility,
      became pregnant after enucleation of the myoma. 2 patients delivered at full
      term, the other two miscarried. 5 out of a total of 10 patients became pregnant
      after endometriosis foci had been coagulated or endometriomas enucleated. In
      these cases, the adnexa did not require additional surgical treatment. Pelviscopy
      revealed an untreatable intratubal block in 9 cases. 10 patients could not be
      included in the study, either because of a successful in vitro fertilisation or a
      pregnancy following heterologous insemination or because a hysterectomy or
      tubectomy had been performed in the meantime. In cases, where inspection under
      magnification had shown at least one non-pathological adnexa and tubal patency of
      at least one of the tubes, 35% of the patients conceived after pelviscopy and
      chromopertubation within the follow-up period. The therapeutic action of the
      chromopertubation and the psychological effect of finding no pathological signs
      during the genital examination remains speculative.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8270153
TI  - [Laparoscopic removal of dermoid cysts].
AB  - Benign dermoid cysts between 1.5 and 6 cm in diameter were laparoscopically
      removed in 9 premenopausal women. Cystectomy was performed in eight patients, and
      unilateral oophorectomy in one. Surgical and postoperative complications were not
      observed. Chemical peritonitis due to the dermoid contents can be avoided,
      provided, careful lavage of the peritoneal cavity is performed.

PMID- 8270154
TI  - [Pelviscopic sacropexy in treatment of vaginal prolapse].
AB  - Although transabdominal sacropexy to correct vaginal prolapse is technically
      simple and yields good results, a minimal invasive procedure is desirable in the
      treatment of this benign condition. We therefore developed a laparoscopic
      sacropexy technique and were able to apply this operation successfully.
      Pelviscopic sacropexy does not differ greatly in principle from the
      intraabdominal approach; however, the techniques used in the individual steps
      must be adapted to pelviscopic methods.

PMID- 8270155
TI  - [Cyclical gestagen (MPA) supplement for continuous transdermal or oral estrogen
      substitution in postmenopause: modification of serum lipids].
AB  - Since postmenopause unopposed oestrogen replacement therapy (ERT) increases the
      incidence of endometrial carcinoma, the addition of a progestin in non
      hysterectomised women is mandatory for hormonal substitution. On the other hand,
      progestins have a negative influence on serum lipids and may thus put in question
      the benefits of the ERT with regard to the cardiovascular risk. Progestins lower
      HDL and increase LDL in a dose-dependent way according to their chemical
      structure. In the present non-randomised study, the influence of a cyclic
      combined oestrogen progestin substitution on the serum lipids has been measured.
      From a total of 90 apparently healthy postmenopausal patients, 59 received a
      transdermal ERT with 17 beta-Estradiol (Estraderm TTS 50), whereas 31 women
      obtained a daily dose of 0.625 mg conjugated equine oestrogens (CE) perorally.
      Additionally all patients were given 10 mg medroxyprogesterone-acetate (MPA)
      daily during the first 10 days of each month. After 6 months of therapy, the
      following changes of serum lipids, expressed as percentage of initial values,
      were measured: total cholesterol in the transdermal group -2.3% (n.s.), in the
      peroral group -11.8% (p < 0.00001); triglycerides -3.7% (n.s.) resp. +8.6%
      (n.s.); HDL cholesterol + 0.2% (n.s.) resp. -1.8% (n.s.); LDL cholesterol +1.3%
      (n.s.) resp. -14.8% (p < 0.00001). The calculated atherogenic indices showed a
      decrease in the peroral substituted group of -6.5% (n.s.) for the HDL/total
      cholesterol ratio and -14.8% (p < 0.002) for the LDL/HDL ratio.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8270156
TI  - [Comparison of preparation techniques with reference to final spermatozoa
      concentration and survival and fertilization rate in vitro in normal and
      pathologic ejaculates].
AB  - Various methods are available in the preparation of normal and pathological
      ejaculates within the framework of available techniques of assisted reproduction.
      The authors examined the recovery rate, the long-term motility and the
      fertilization rate in vitro after both normal and pathological test results, of
      preparations, using one of the three most commonly used techniques.
      Centrifugation with its resulting swim up (Z) is a method still widely used
      because of the good sperm recovery rate it produces. However, in our tests, it
      achieved the lowest level capacity, compared with sperm separation by
      migration/sedimentation, with resultant swim up (M) and Percoll gradient
      centrifugation (P). The statistically highly significant fast decline of motility
      after preparation by Z, compared with the other two above mentioned techniques,
      in both normal and pathological ejaculates is a further indication, that Z has a
      negative influence upon the integrity of the spermatozoa. The results of research
      submitted here suggest the abandonment of Z in its standard form in favour of
      other techniques. After normal test results, both M and P might be used, but in
      the case of pathological ejaculate, P would be recommended.

PMID- 8270157
TI  - [Phthirus pubis as the cause of tubo-ovarian conglomerate tumor].
AB  - A case of an inflammatory tubo-ovarian tumour is presented. Histology and
      entomology identified the infectious agent as Phthirus pubis.

PMID- 8270158
TI  - [Erosion of the uterine artery--an unusual late complication 19 weeks after
      Cesarean section].
AB  - In a 30-year old para I, following uncomplicated Caesarean section in late
      pregnancy, recurrent haemorrhage occurred, which finally peaked as an arterial
      mass bleeding. The diagnosis of an arrosion of a large branch of the uterine
      artery was made by clinical and sonographic means. Therapy consisted in operative
      revision of the uterotomy and the uterus is saved. The possible causes of
      bleeding in the late puerperium are discussed.

PMID- 8270159
TI  - [Diabetes insipidus--a rare complication post partum].
AB  - A report is made on the manifestation of diabetes insipidus (neuropituitary
      syndrome), observed six days after a Caesarean section (29-years old I. Gravida).
      The progress of pregnancy and delivery as well as the successful treatment with
      Desmopressin (Minirin) post partum are described. The aetiology is still obscure.

PMID- 8270160
TI  - [Society of Obstetrics and Gynecology in Berlin. Meeting 2 December 1992].

PMID- 8270161
TI  - Active translocation of platelets into sinusoidal and Disse spaces in the liver
      in response to lipopolysaccharides, interleukin-1 and tumor necrosis factor.
AB  - 1. Injection of lipopolysaccharides (LPS) or endotoxin into mice and rats induces
      a prolonged increase in serotonin (5-hydroxytryptamine: 5HT), predominantly in
      the liver. 2. The 5HT increase reflects the accumulation of platelets in the
      sinusoidal and perisinusoidal Disse spaces (spaces between endothelial cells and
      hepatocytes) in the liver. 3. Most of the platelets which accumulated in these
      spaces still retained their intact structure and a large amount of 5HT. 4.
      Interleukin-1 and/or tumor necrosis factor also induce the platelet response. 5.
      Kupffer's cells play a key role in this platelet response. 6. Anti-platelet drugs
      currently used, except for anti-inflammatory steroids, were ineffective in
      preventing the platelet response. 7. This platelet response is different from the
      well known platelet aggregation. 8. The possible involvement of this platelet
      response in insulin-independent hypoglycaemia, disseminated intravascular
      coagulation, septic shock, hepatitis, Shwartzman type reactions or self-defense
      mechanisms is discussed.

PMID- 8270162
TI  - Pharmacological aspects of gonadal alcohol and aldehyde-dehydrogenase.
AB  - 1. A brief overview of gonadal alcohol dehydrogenase (ADH) and aldehyde
      dehydrogenase (ALDH) is presented and their relationships to gonadal toxicity of
      ethanol has been discussed. 2. The distributions of ADH and ALDH among major
      reproductive tissues of rodents, their subcellular localization and kinetic
      properties were summarized. 3. The sensitivity of testicular ADH and ALDH to
      ethanol intake, various psychoactive agents and steroidal compounds was assessed
      and the implication of these enzymes in gonadal ethanol-drug interaction has been
      suggested. 4. The possible role of testicular ALDH in tumorigenesis and in high
      altitude endocrine sensitivity to ethanol has been addressed.

PMID- 8270163
TI  - Extracellular matrix components and amyloid in neuritic plaques of Alzheimer's
      disease.
AB  - 1. There has been an enormous amount of information relating to the molecular
      components involved in Alzheimer's disease. 2. Recently some attention has been
      focused on the extracellular matrix (ECM) components present in the brain amyloid
      deposits. 3. Here we discuss, the direct involvement of ECM constituents such as
      laminin, collagen type IV, fibronectin, proteoglycans (PGs) and basic fibroblast
      growth factor in the formation of neuritic plaques. 4. We suggest that PGs act as
      nucleating agents in the formation of the diffuse amyloid deposits that precede
      the formation of the neuritic plaque in the brain of patients affected with
      Alzheimer's disease.

PMID- 8270164
TI  - Ca(2+)- and Na(+)-dependent depolarization induced by maitotoxin in the crayfish
      giant axon.
AB  - 1. Maitotoxin (MTX) depolarized the membrane of the crayfish giant axon and
      decreased the amplitude and maximum rate of rise of action potentials in an
      irreversible manner. 2. The depolarizing action of MTX was attenuated in low Ca
      (1 mM; 1/10 of normal concentration) solution and was also inhibited by 2 mM
      Co2+, 300 microM Ni/+, 1 microM nifedipine, 10 microM verapamil or 1 microM
      tetrodotoxin. 3. These results suggest that the depolarization by MTX in the
      crayfish giant axon may be related to changes not only in Ca permeability but
      also in Na permeability, possibly through the modification of existing Na or Ca
      channels and/or a new type of channel or pore induced by MTX.

PMID- 8270165
TI  - All-or-none shortening of isolated single smooth muscle cells from different
      organs to acetylcholine.
AB  - 1. Single smooth muscle cells from the guinea-pig taenia caecum and the fundus of
      guinea-pig stomach were prepared by collagenase digestion under different, mild
      conditions. 2. Most of the cells either from taenia caecum or from the fundus of
      stomach responded repeatedly, showing an all-or-none response to acetylcholine
      (ACh). 3. The threshold concentrations of ACh were different for the cells of the
      two tissues. Although individual cells showed an all-or-none response to ACh, the
      average responses of all the cells were graded, like that of whole tissues. 4.
      Thus, isolated single smooth muscle cells from different tissues and under
      different conditions responded to ACh in an all-or-none manner such as the twitch
      observed in skeletal muscle. 5. These results suggest that the isolation of cells
      reveals the fundamental characteristics of smooth muscle cells as excitable.

PMID- 8270166
TI  - Comparison among the effects of nifedipine, nimodipine and nisoldipine on the
      brain biogenic amines of normal or haloperidol treated rats.
AB  - 1. Previous studies have shown that dihydropyridine calcium antagonists affected
      the metabolism of the brain biogenic amines more extensively than the non
      dihydropyridine ones. The effects of three dihydropyridines (nifedipine,
      nimodipine or nisoldipine, 0.05-0.10 mmol/kg i.p.) on brain monoamines and
      metabolites have been evaluated on both normal and haloperidol treated rats. 2.
      The small changes induced by the drugs on normal rats were markedly increased in
      the haloperidol treated rats, clearly showing an inhibition of dopaminergic
      systems. 3. These effects were selective for the striatum and cerebral cortex,
      with nisoldipine being more effective than nimodipine or nifedipine. 4. The
      effects of the three drugs on serotonergic systems were similar or more marked on
      haloperidol treated rats than on normal rats. These effects, showing activation
      of serotonergic systems, displayed some regional specificity and different
      potency of the three compounds. Nisoldipine also appeared to be the most
      effective drug on serotonergic systems. 5. In conclusion nisoldipine, as well as
      other calcium antagonists, may have a place in the treatment of some mood
      disorders.

PMID- 8270167
TI  - ATP4- increases the intracellular calcium concentration in rat submandibular
      glands.
AB  - 1. The intracellular calcium concentration of a crude suspension from rat
      submandibular glands was increased by extracellular ATP. 2. The stimulatory
      effect of ATP was favored by removal of magnesium from the extracellular medium.
      ADP and adenosine had no effect. ATP did not modify the concentration of calcium
      in isolated rat pancreatic acini. 3. It is concluded that ATP is a potential
      neurotransmitter regulating the submandibular gland function.

PMID- 8270168
TI  - Comparative effects of velnacrine, tacrine and physostigmine on the twitch
      responses in the rat phrenic-hemidiaphragm preparation.
AB  - 1. Cholinesterase inhibitors potentiated twitch responses induced by nerve
      stimulation, with physostigmine more potent than tacrine and velnacrine. However,
      at higher concentrations, tacrine decreased twitch responses in a concentration
      dependent manner. 2. Tacrine strongly depressed directly-induced twitch
      responses, whereas the other drugs had minimal effects. 3. Physostigmine was the
      most potent drug in reversal of tubocurarine-induced blockade, but its antagonism
      index was similar to those obtained with tacrine and velnacrine at higher
      concentrations. When evaluating their ability to reverse neomycin-induced
      blockade, all drugs exhibited a similar effect. 4. It is concluded that tacrine
      and velnacrine are less potent than physostigmine in potentiating skeletal
      neuromuscular transmission. Additionally, the blocking effects of tacrine could
      limit its therapeutic efficacy.

PMID- 8270169
TI  - Tylophora compounds as Na+/K(+)-ATPase inhibitors.
AB  - 1. Acetyltylophoroside (AcT) and tylogenin inhibit Na+/K(+)-ATPase in spite of
      having structures very different from cardiac glycosides (CGs). 2. Calculation of
      the lowest energy conformations of AcT and tylogenin and superpositions of these
      with the X-ray conformations of CGs and chlormadinone acetate led to a model for
      the interaction of these different types of Na+/K(+)-ATPase inhibitors with the
      receptor.

PMID- 8270170
TI  - The respiratory effects of the volatile oil of the black seed (Nigella sativa) in
      guinea-pigs: elucidation of the mechanism(s) of action.
AB  - 1. The effect of the volatile oil (VO) of the black seed (Nigella sativa) on the
      respiratory system of the urethane-anaesthetized guinea-pig was investigated and
      compared with those of its constituent thymoquinone (TQ). 2. Intravenous
      administration of VO in the dose range (4-32 microliters kg-1) induced dose
      dependent increases in the respiratory rate and the intratracheal pressure. 3.
      The effects of VO were significantly antagonized by treatment of the animals with
      mepyramine, atropine and reserpine. They were not antagonized by indomethacin,
      diethyl carbamazine or hydrocortisone. 4. Intravenous administration of TQ in the
      dose range (1.6-6.4 mg kg-1) induced significant increases in the intratracheal
      pressure without any effect in the respiratory rate. 5. The results suggested
      that VO-induced respiratory effects were mediated via release of histamine with
      direct involvement of histaminergic mechanisms and indirect activation of
      muscarinic cholinergic mechanisms. 6. Removal of TQ from VO may provide a
      potential centrally acting respiratory stimulant.

PMID- 8270171
TI  - The cardiovascular actions of the volatile oil of the black seed (Nigella sativa)
      in rats: elucidation of the mechanism of action.
AB  - 1. The effects of the volatile oil (V.O.) of the black seed (Nigella sativa) on
      the arterial blood pressure and heart of urethane-anaesthetized rats were
      investigated and the effects were compared with those of its constituent
      thymoquinone (T.Q.). 2. Intravenous administration of V.O. in the dose range (4
      32 microliters kg.-1) or T.Q. (0.2-1.6 mg kg-1) to rats decreased the arterial
      blood pressure and the heart rate in a dose-dependent manner. 3. The effects of
      V.O. were significantly antagonized by treatment of the animals with
      cyproheptadine, hexamethonium atropine and by spinal pithing. 4. Treatment of the
      animals with reserpine (5 mg kg- 1 day-1 for 2 days) significantly antagonized
      the cardiovascular depressant effects induced by 4 and 8 microliters of V.O. kg-1
      but not those induced by the larger doses. 5. T.Q.-induced cardiovascular
      depressant effects were significantly antagonized by atropine and cyproheptadine
      but not by reserpine. 6. The results suggested that V.O.-induced cardiovascular
      depressant effects were mediated mainly centrally via indirect and direct
      mechanisms that involved both 5-hydroxytryptaminergic and muscarinic mechanisms.
      The direct mechanisms may be due to the presence of T.Q. in the V.O. The V.O.
      seemed to possess the potential of being a potent centrally acting
      antihypertensive agent.

PMID- 8270172
TI  - Alteration of in vitro bone metabolism and tooth formation by zinc.
AB  - 1. The effects of zinc on bone metabolism and tooth formation was examined in
      organ cultures of calvaria and tooth germ, and in cell cultures of osteoblast
      like cells, MC3T3-E1. 2. Treatment of calvaria with zinc (10, 100 microM) for 4
      days both increased alkaline phosphatase (ALP) activity in bone and reduced the
      secretion of N-acetyl beta-glucosaminidase from bone, without affecting bone
      mineral or collagen content. The increase in ALP activity produced by zinc (10
      microM) was inhibited neither by actinomycin D (5 micrograms/ml) nor by
      cycloheximide (0.5 micrograms/ml). 3. Treatment of MC3T3-E1 cells with zinc (50,
      100 microM) for 25 days also increased ALP activity, but reduced calcium content
      in cells and in the matrix layer. 4. These results indicate that zinc increases
      ALP activity in osteoblasts without affecting de novo enzyme synthesis, and that
      it inhibits bone mineralization, in accordance with the inhibition of
      osteoclastic activity. 5. Treatment of tooth germ with zinc (100 microM) for 7
      days also produced an increase in ALP activity and inhibition of mineralization.
      These results indicate that the increased ALP activity produced by zinc is a
      common phenomenon in hard tissues, and, further, that zinc inhibits
      mineralization during tissue formation.

PMID- 8270173
TI  - The behavioral effects of serotonin synthesis inhibition and quisqualic acid
      induced lesions of the nucleus basalis magnocellularis in rats.
AB  - 1. To investigate the role of the cholinergic and serotonergic systems in the
      regulation of cognitive functions, the effects of concurrent lesioning of nucleus
      basalis magnocellularis (NB) with quisqualic acid (quis) and inhibition of brain
      serotonin synthesis by systemic p-chlorophenylalanine (PCPA) treatment on passive
      avoidance (PA) retention and water maze (WM) spatial navigation performance were
      studied in rats. 2. Quis NB lesioning induced a marked reduction (-62%) in
      frontal cortical choline-acetyltransferase activity, impaired retention of PA,
      and slightly and transiently impaired acquisition of WM spatial navigation. 3.
      PCPA (400 mg/kg/day x 3, i.p.) treatment depleted frontal cortical concentrations
      of both serotonin (82% depletion) and its major metabolite 5-HIAA (90% depletion)
      and slightly affected the noradrenergic and dopaminergic systems. PCPA treatment
      alone had no effect on WM or PA behavior, but potentiated the PA retention
      deficit and slightly aggravated the WM deficit in rats subjected to quis NB
      lesioning. 4. The present results further support the view that serotonergic and
      NB neurons interact in the regulation of cognitive functions.

PMID- 8270174
TI  - Alpha 1-adrenoceptor subtypes mediating the norepinephrine-induced contractile
      response in the rat vas deferens.
AB  - 1. The effects of chlorethylclonidine (CEC), 5-methyl-urapidil (5-MU), ryanodine
      and prolonged exposition to norepinephrine (NE) on the concentration-response
      curves (CRC) to this agonist on the bisected rat vas deferens (RVD) were
      investigated. 2. CEC did not affect the 50% effective concentration (EC50) of NE
      in either the prostatic (PP) or the epididymal (EP) portions of the RVD. 3. 5-MU
      did not alter the EC50 of NE in the PP but caused a significant and concentration
      dependent rightward shift of the CRC to NE in the EP. 4. Ryanodine caused a shift
      to the right of the CRC to NE in the PP associated to a decrease in maximal
      response, but did not affect the CRC to NE in the EP. 5. Incubation of the EP
      with NE for 6 hr elicited a significant decrease in the maximal response with no
      changes in the EC50. Similar treatment of the PP was associated with a
      significant shift to the right of the CRC to NE without modifications in the
      maximal response. 6. These results suggest that in the RVD, NE interacts with two
      different alpha 1-adrenoceptors subtypes which are disposed in a selective manner
      along the RVD: the alpha 1(a) subtype in the EP, and non-alpha 1b-non-alpha 1a
      adrenoceptor subtype mainly located at the PP.

PMID- 8270175
TI  - Cellular mechanisms of the steroid-induced vascular responses in the rabbit ear
      artery.
AB  - 1. In anesthetized rabbits, topical application of dexamethasone to the ear
      produced an initial vasodilation followed by a vasoconstriction with long delay
      (120 min). Diphenhydramine inhibited the former, but not the latter. 2. In
      isolated rabbit ear arteries, dexamethasone reduced the amplitude of contractions
      of smooth muscles produced by nerve stimulation, noradrenaline and high-K
      solution, only at high concentrations (> 10(-5) M). 3. The initial vasodilation
      induced by topical application of dexamethasone may be related to endogenous
      histamine, while the delayed constriction response may not be direct actions of
      steroid to smooth muscles.

PMID- 8270176
TI  - The topical application of verapamil and nifedipine lowers intraocular pressure
      in conscious rabbits.
AB  - 1. The time-course of the ocular effects of topical verapamil and nifedipine as
      well as the dose-response relationship, were studied in conscious, normotensive
      rabbits. 2. Both drugs caused a dose-dependent fall of intraocular pressure,
      which lasted 4 hr or more. 3. Log dose-response curves of both drugs show a
      similar peak response, but the potency of verapamil was greater that of
      nifedipine. 4. A fall in the intraocular pressure in the untreated eye was also
      observed. 5. Verapamil and nifedipine induced a reduction of the tonographic
      outflow facility in the treated eye.

PMID- 8270177
TI  - Comparative studies with 15(R)-15-methylprostaglandin E2 (arbaprostil) in rat
      femoral arterial preparations in vivo and in vitro.
AB  - 1. The vasodilator responses to 15(R)-15-methylprostaglandin E2 (arbaprostil),
      prostaglandin (PG) E2 and acetylcholine (ACh) administered into the femoral
      artery intra-arterial (i.a.) of anesthetized rats were attenuated by i.a.
      infusion of methylene blue, while that to nicardipine remained unaffected in the
      same dose-range of methylene blue. 2. The vasocontractor responses to arbaprostil
      and PGE2 in isolated femoral arterial strips were significantly potentiated by
      removal of the endothelium and the presence of NG-monomethyl L-arginine, while
      that to U-46619 remained unaffected under the same condition. 3. The present
      result indicates that the endothelium-dependent mechanism may play an important
      role in the vascular response to arbaprostil, like PGE2 and ACh.

PMID- 8270178
TI  - Bepridil prolongs the action potential duration of guinea pig ventricular muscle
      only at rapid rates of stimulation.
AB  - 1. We examined the electromechanical effects of the calcium antagonist, bepridil
      (1-20 microM), on isolated guinea pig ventricular muscles, driven at various
      stimulus frequencies (0.1, 0.5, 1, 2 and 5 Hz) in Tyrode's solution containing
      various K+ concentrations (1.4-43.2 mM). 2. Conventional microelectrode and
      tension-recording techniques were used. 3. We found that bepridil decreased the
      maximum upstroke velocity (Vmax) of the action potential with no change in the
      resting membrane potential (RMP). 4. The former effect depended on both stimulus
      frequency and the drug concentration used. 5. Bepridil lengthened the duration of
      the action potential at the level of 25% repolarization (APD25) at the highest
      frequency (5 Hz), but shortened it at lower frequencies (< or = 2 Hz). 6. The
      drug also lengthened the APD90 at the highest frequency (5 Hz) but without
      significant effect at lower frequencies (< or = 2 Hz). 7. Bepridil depolarized
      the RMP at relatively low extracellular K+ concentrations (< or = 2.7 mM),
      accompanied by a prolongation of APD90. 8. There were no such effects at much
      higher K+ concentrations (> or = 5.4 mM), and the drug markedly depressed the
      Vmax and the action potential amplitude. 9. The drug eliminated the positive
      staircase phenomenon of twitch contraction, in a concentration-dependent manner.
      10. All these findings taken together suggest that bepridil prolongs the action
      potential duration by inhibiting outward potassium currents (IK and IK1), at
      rapid rates of stimulation (approximately 300/min), which is comparable to the
      physiological heart rate of a guinea pig. 11. The prolongation of APD seemed to
      be secondary to the bepridil-induced reduction of intracellular Ca2+
      concentration, [Ca2+]i.

PMID- 8270179
TI  - Phospholipase A2-induced hypotension in the rat and its pharmacological
      modulation.
AB  - 1. An increase in circulating levels of extracellular group II phospholipase A2
      (PLA2) has been detected in patients with septic shock as well as in rats,
      rabbits and human volunteers following intravenous endotoxin administration. 2.
      Group II PLA2 from Naja mocambique mocambique (NajaPLA2) snake venom (1-10
      micrograms i.v.) induced a dose-dependent hypotension and leucopenia in the rat
      similar to that induced by intravenous administration of endotoxin. 3. NajaPLA2
      did not aggregate rat platelet, but did aggregate purified rat neutrophils in
      vitro. However intravenous PLA2 caused rat platelets to aggregate in vivo. 4. The
      hypotensive effect was reduced either by inactivating NajaPLA2 in vitro with para
      bromophenacyl bromide or by infusing in vivo polyclonal rabbit antiPLA2 antisera.
      Neither the hypotension nor the leucopenia was affected by several agonists and
      inhibitors. 5. The leukotriene D4 antagonist L-649,923 produced a dose-related (5
      20 mg/kg i.v.) inhibition of NajaPLA2-induced hypotension while the dual
      inhibitor of lipo- and cyclooxygenase BW755c (5-50 mg/kg i.v.) was ineffective.
      6. In rats rendered leucopenic with methotrexate the L-649,923 was ineffective
      implying that the L-649,923 effect could be partially mediated through its action
      on neutrophils.

PMID- 8270180
TI  - Calcium channel antagonists and adenosine analogues decrease tolerance to opiate
      pentazocine and U 50488H.
AB  - 1. A single dose of pentazocine induces cross-tolerance the analgesic effects of
      the kappa agonist U 50488H. Tolerance is observed by means of the hot plate test
      or by the i.p. administration of acetic acid 6 or 24 hr after the priming dose,
      respectively. 2. The administration of the calcium channel antagonists,
      diltiazem, nifedipine or verapamil, reduces the degree of tolerance as assessed
      by the hot plate test or acetic acid administration. 3. The adenosine agonist N6
      cyclopentyl adenosine significantly reduced the intensity of the process; in
      contrast, N6-cyclohexyladenosine antagonized the analgesic response to the opiate
      obscuring its influence on the process. 4. The results are discussed in relation
      to the interaction of calcium channel function in the analgesic response to the
      kappa opiates.

PMID- 8270181
TI  - Positive and negative chronotropic effects of caffeine in spontaneously beating
      rabbit sino-atrial node cells.
AB  - 1. Effects of caffeine on the automaticity in spontaneously beating rabbit sino
      atrial node cells were examined. 2. Caffeine (0.5-2 mM) caused only a positive
      chronotropic effect. At over 5 mM, caffeine caused an initial positive and
      subsequently a negative chronotropic effect. Both were not modified by pindolol
      (1 microM) and atropine (1 microM). 3. At 10 mM, a dysrhythmia occurred in all 9
      preparations. The effects were reversible, and dysrhythmia also disappeared after
      washout. 4. When extracellular K+ was increased from 2.7 to 8 mM, the dysrhythmia
      induced by caffeine (10 mM) was abolished, and the sinus rate was increased. 5.
      Addition of tetrodotoxin (TTX) (10(-7) M) in the presence of caffeine (10 mM)
      also abolished the dysrhythmia and increased the sinus rate. 6. In addition, a
      decrease in extracellular Ca2+ ([Ca]o) to 0.5 mM abolished the dysrhythmia and
      increased the sinus rate, whereas increasing [Ca]o to 7.4 mM potentiated the
      negative chronotropic effect and failed to inhibit the dysrhythmia. 7. These
      results indicate that the positive chronotropic effect is due to the stimulatory
      effect of caffeine, and the negative effect is directly and indirectly due to
      development of cellular calcium overload.

PMID- 8270182
TI  - Beta-endorphin levels in women with elevated prolactin and following
      bromocriptine therapy.
AB  - 1. Plasma levels of beta-endorphin were not significantly different in women with
      normal plasma prolactin or women with hyperprolactinemia. 2. A bromocriptine
      induced decrease in plasma prolactin was not accompanied by a decrease in beta
      endorphin. 3. This study suggests that no direct link exists between plasma
      prolactin levels and endogenous beta-endorphin.

PMID- 8270183
TI  - 12-Lipoxygenase product as an inhibitor of the action of chemoattractant peptide
      fMet-Leu-Phe in rat neutrophils.
AB  - 1. 12-Hydroxyeicosatetraenoic acid (12-HETE) has been evaluated for its
      capacities to modulate neutrophil migration and cytosolic Ca2+ ([Ca2+]i) using
      compounds prepared by chemical synthesis and tissue extract from dog gingiva. 2.
      12-HETE inhibited N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophil migration in
      a concentration-dependent fashion. 3. The tissue extract from dog gingiva
      mimicked the actions of 12-HETE. 4. Although 12-HETE failed to increase [Ca2+]i,
      preincubation of neutrophils with 12-HETE led to a suppression of [Ca2+]i when
      the cells were subsequently stimulated by fMLP. 5. Again tissue extract from dog
      gingiva mimicked the action of 12-HETE on [Ca2+]i. 6. These results suggest the
      possible correlation of the inhibitory activities of 12-HETE on the regulation of
      neutrophil migration and Ca2+ mobilization, and this may be important for the
      role of 12-HETE in pathogenesis in periodontal tissues.

PMID- 8270184
TI  - Comparative effects of the anticholinesterase drug galanthamine on the mechanical
      activity of isolated rat jejunum and ileum.
AB  - 1. The effects of cumulatively applied galanthamine hydrobromide (0.1-300 microM)
      on the mechanical activity of isolated proximal jejunum and distal ileum were
      studied. 2. Galanthamine was found to increase the spontaneous mechanical
      activity and exert by itself an enhancement of the smooth muscle tone in the two
      segments, both effects being more pronounced in ileum than in jejunum. 3. The
      galanthamine-induced augmentation of the spontaneous mechanical activity was
      tetrodotoxin (TTX)-sensitive, whereas the contractile effect of the drug on the
      tone was TTX-insensitive in both segments. 4. The present results showed not only
      quantitative differences in the tonic effects of galanthamine in both intestinal
      segments but they suggest some qualitative differences in cholinergic neuronal
      control along the gastro-intestinal tract.

PMID- 8270185
TI  - Characterization of the calcium and chloride [3H]glutamate binding site in crude
      synaptic membranes from human brain tissue.
AB  - 1. The specific binding properties of [3H]glutamate to crude synaptic membranes
      (CSM) from postmortem human brain were studied. 2. Equilibrium binding analysis
      of [3H]glutamate binding to CSM from human brain cortex revealed a KD = 110 +/-
      12 nM and a Bmax = 27 +/- 4 pmol/mg protein). 3. Calcium increased the number of
      binding sites, Bmax = 44 +/- 6 pmol/mg protein, without a significant change in
      the affinity constant, KD = 95 +/- 10 nM. 4. The dissociation constant of the
      [3H]glutamate bound to human CSM was 4.0 +/- 0.4 min-1 (n = 3). 5. The relative
      potencies of glutamate analogs and 2-amino-4-phosphonobutyric acid (APB) to
      compete for the glutamate binding sites, in human CSM, were glutamate >
      quisqualate = ibotenic acid > APB >> alpha-amino-3-hydroxy-5-methyl-4
      isoxozolepropionate acid. 6. The glutamate specific binding in CSM from
      postmortem human brain was particularly rich in the gyrus hippocampus, nucleus
      accumbens, thalamus and frontal cortex. 7. This glutamate binding protein is
      related, probably, to a presynaptic neurosecretory pathway.

PMID- 8270186
TI  - Strain differences in change in airway responsiveness after repeated antigenic
      challenge in three strains of rats.
AB  - 1. The strain differences in 2,4-dinitrophenylated-Ascaris antigen-induced airway
      hyperresponsiveness (AHR) were investigated in three strains of rats: Brown
      Norway (BN), Long-Evans Cinnamon (LEC) and Wistar. 2. Fourty-eight hour-passive
      cutaneous anaphylaxis titers after repeated challenge were highest in BN and
      lowest in LEC. 3. Twenty-four hours after the last challenge, a marked AHR and
      significant increase in wet/dry weight ratio of the main bronchus were observed
      only in Wistar. 4. Only the isolated bronchus of the challenged Wistar among the
      strains showed hyperresponsiveness to acetylcholine. 5. Wistar may be the best
      strain for antigen-induced AHR.

PMID- 8270187
TI  - Comparative modulating effects of captopril, diltiazem, dietary calcium and
      pyridoxal-5'-phosphate on gentamicin-induced nephrotoxicity in the rat.
AB  - 1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly
      (i.m.) at a dose of 80 mg/kg/day for 6 days. Treated animals demonstrated a
      typical pattern of aminoglycoside nephrotoxicity characterized
      histopathologically by necrosis of proximal tubular epithelium, and biochemically
      by increased serum creatinine and urea concentrations. Reduced glutathione (GSH)
      concentration in renal cortex was significantly decreased by gentamicin. 2.
      Simultaneous treatment of rats with gentamicin and either captopril or diltiazem
      significantly potentiated the gentamicin-induced increases in serum creatinine
      and urea and did not significantly affect the gentamicin-induced decrease in
      cortical GSH concentration. 3. Concomitant treatment with gentamicin and either
      Ca2+ or pyridoxal-5'-phosphate decreased serum urea level, did not significantly
      affect serum creatinine concentration, and significantly increased cortical GSH
      concentration in comparison to the values of these parameters following
      gentamicin treatment. 4. Histopathologically, the severity of gentamicin-induced
      renal damage was exacerbated by captopril, and even more so by diltiazem.
      Simultaneous treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate
      produced only mild focal atrophy of renal tubular epithelium. Control rats had
      apparently normal histology. 5. In conclusion, captopril and diltiazem, at the
      doses used, significantly potentiated gentamicin-induced nephrotoxicity to a
      broadly similar extent. Although Ca2+ and pyridoxal-5'-phosphate, at the doses
      used, reduced significantly the severity of some of the manifestations of
      nephrotoxicity, they were equally ineffective in completely preventing the
      development of nephrotoxicity.

PMID- 8270188
TI  - Effects of cryptolepine on collagen-induced aggregation and on the mobilization
      and metabolism of arachidonic acid by rabbit platelets.
AB  - 1. We examined the effect of cryptolepine on collagen-induced aggregation and on
      the mobilization, and metabolism of arachidonic acid in rabbit platelets. 2.
      Preincubation of platelets with cryptolepine (50-100 microM) did not affect the
      primary wave of aggregation but resulted in a dose-dependent, surmountable
      inhibition of the secondary wave of aggregation induced by collagen (5
      micrograms/ml). The inhibition by cryptolepine was greater when cryptolepine was
      incubated with the platelets after the peak of the primary wave of aggregation.
      3. Cryptolepine (50-100 microM) dose-dependently inhibited thrombin (1.5 U/ml)
      and A23187 (2.5 microM)-induced release of 14C[AA] from platelet membrane
      phospholipid pools. The percentage inhibition of A23187-induced 14C[AA] release
      was 31.3 +/- 4.3% (50 microM) and 79.3 +/- 5.4% (100 microM), while thrombin
      induced release was inhibited by 39.2 +/- 2.4% (50 microM) and 68.2 +/- 3.6% (100
      microM). 4. At near maximal concentration (100 microM) which significantly
      inhibited secondary aggregatory response and 14C[AA] release, cryptolepine had no
      effect on the platelet metabolism of 14C[AA] to thromboxane B2, HHT and 12 HETE.
      5. The present findings suggest that cryptolepine inhibited collagen-induced
      secondary aggregation through a selective antiphospholipase-like activity. There
      was no effect on platelet cyclooxygenase and lipoxygenase activities of
      platelets.

PMID- 8270189
TI  - Site-directed mutagenesis of dicarboxylic acid residues of the penicillin-binding
      module of the Escherichia coli penicillin-binding protein 3.
AB  - The glutamic acid E396, aspartic acid D409 and glutamic acid E411 residues of the
      Escherichia coli penicillin-binding protein 3 were each converted into an alanine
      residue. As deduced from penicillin-binding and complementation experiments, none
      of these dicarboxylic acid residues is involved in the mechanism of acylation by
      penicillin and none of them is essential for the in vivo functioning of the PBP.
      The mutation E396, however, causes an increased thermolability of the protein.

PMID- 8270190
TI  - Isolation and preliminary characterisation of twenty-five temperature-sensitive
      mutants of mouse cytomegalovirus.
AB  - To study the pathogenicity of mouse cytomegalovirus (MCMV) and to identify
      virulence determinants, we have isolated and phenotypically characterised 25
      temperature-sensitive (ts) mutants. Six of these (tsm9, tsm13, tsm20, tsm22,
      tsm28 and tsm30) failed to replicate in mice and were avirulent. Five mutants
      (tsm14, tsm18, tsm19, tsm25 and tsm27) were of similar virulence to the parental
      wild-type (wt) virus, five (tsm7, tsm15, tsm24, tsm26 and tsm31) were 12-100 fold
      less virulent, five (tsm8, tsm12, tsm16, tsm23 and tsm29) were 150-1500 fold less
      virulent and four (tsm10, tsm11, tsm17 and tsm21) were between 2,000 and 85,000
      fold less virulent than wt. One mutant (tsm28) did not plaque or replicate at 39
      degrees C while 5 other mutants (tsm7, tsm9, tsm23, tsm24 and tsm27) also failed
      to plaque at 39 degrees C but only failed to replicate or replicated poorly at 40
      degrees C. A further two mutants (tsm10 and tsm13) were able to plaque and
      replicate at 39 degrees C but not 40 degrees C. Six other mutants (tsm14, tsm15,
      tsm16, tsm21, tsm22 and tsm30) failed to form plaques at 40 degrees C and were
      severely restricted in their replication at 40 degrees C. The remaining 11
      mutants exhibited varying degrees of restriction in ability to plaque and/or
      replicate at non-permissive temperatures. These 25 mutants, together with 6
      isolated previously, comprise at least 24 complementation groups.

PMID- 8270191
TI  - Stationary phase-specific expression of the fic gene in Escherichia coli K-12 is
      controlled by the rpoS gene product (sigma 38).
AB  - The fic gene, near pabA located at 75 min of the Escherichia coli chromosome, was
      previously identified as the regulatory factor of cell division. In this paper we
      have examined how fic gene expression is controlled during the growth cycle using
      a fic-lacZ protein fusion plasmid (pFL1). Its expression was induced at
      stationary phase while it was nearly abolished in rpoSmutants. Using a RNase
      protection assay, fic transcript at stationary phase was detected in rpoS+
      strains, but not in the rpoS mutants. Furthermore, primer extension analysis
      indicated that the fic transcript controlled by RpoS initiates at a G located 185
      bp upstream from ATG of the fic coding region. Compared with the sigma 70
      recognition sequence, the -10 region of fic promoter resembled the Pribnow box,
      but no homologous sequence was observed at the -35 region. These results were
      consistent with the characteristic sequence profile of fic promoter recognized
      specifically by RpoS in vitro, which is the only example of the type III promoter
      so far detected in vitro and in vivo.

PMID- 8270192
TI  - Synthesis of the K5 (group II) capsular polysaccharide in transport-deficient
      recombinant Escherichia coli.
AB  - The genes directing the expression of group II capsules in Escherichia coli are
      organized into three regions. The central region 2 is type specific and thought
      to determine the synthesis of the respective polysaccharide, whilst the flanking
      regions 1 and 3 are common to all group II gene clusters and direct the surface
      expression of the capsular polysaccharide. In this communication we analyze the
      involvement of region 1 and 3 genes in the synthesis of the capsular KS
      polysaccharide. Recombinant E. coli strains harboring all KS specific region 2
      genes and having various combinations of region 1 and 3 genes were studied using
      immunoelectron microscopy. Membranes from these bacteria were incubated with
      UDP[14C]GlcA and UDPGlcNAc in the absence or presence of KS polysaccharide as an
      exogenous acceptor. It was found that recombinant strains with only gene region 2
      did not produce the K5 polysaccharide. Membranes of such strains did not
      synthesize the polymer and did not elongate K5 polysaccharide added as an
      exogenous acceptor. An involvement of genes from region 1 (notably kpsC and kpsS)
      and from region 3 (notably kpsT) in the K5 polysaccharide synthesis was apparent
      and is discussed.

PMID- 8270193
TI  - Phase variation of lipopolysaccharide of Coxiella burnetii, strain Priscilla
      during chick embryo yolk sac passaging.
AB  - Changes of lipopolysaccharide (LPS) of Coxiella burnetii strain Priscilla during
      chick embryo yolk sac passaging were observed by SDS-PAGE and immunoblot
      analysis. The course of LPS phase variation was similar to that found in other C.
      burnetti strains, i.e. a conversion of the phase I to the intermediate phase II
      after 10 passages. The intermediate phase II LPS of Priscilla strain was also
      detectable by immunoblot analysis using immune serum against Priscilla strain in
      the 30th passage.

PMID- 8270194
TI  - Xylose and arabinose utilization by the rumen bacterium Butyrivibrio
      fibrisolvens.
AB  - The rumen bacterium Butyrivibrio fibrisolvens strain D1 co-utilized xylose and
      glucose in batch culture, but there was a marked preference for glucose over
      arabinose. When both pentoses were provided, xylose was preferred over arabinose.
      Strain D1 co-utilized a combination of either pentose and cellobiose, but
      preferred over maltose. Pentose sugars were depleted less rapidly in the presence
      of sucrose than controls containing only pentose. In contrast, B. fibrisolvens
      strain A38 exhibited a strong preference for disaccharides, including maltose,
      over either xylose or arabinose. Theoretical maximum growth yields for strain D1
      in single-substrate continuous culture were highest for sucrose and cellobiose
      and the maintenance energy coefficient for arabinose was at least 3.8-fold
      greater than for other substrates. We suggest that B. fibrisolvens may have
      evolved a mechanism to utilize certain sugars before arabinose in order to avoid
      this high maintenance energy expenditure.

PMID- 8270195
TI  - Oxidation of carbazole to 3-hydroxycarbazole by naphthalene 1,2-dioxygenase and
      biphenyl 2,3-dioxygenase.
AB  - Naphthalene 1,2-dioxygenase from Pseudomonas sp. NCIB 9816-4 and biphenyl
      dioxygenase from Beijerinckia sp. B8/36 oxidized the aromatic N-heterocycle
      carbazole to 3-hydroxycarbazole. Toluene dioxygenase from Pseudomonas putida
      F39/D did not oxidize carbazole. Transformations were carried out by mutant
      strains which oxidize naphthalene and biphenyl to cis-dihydrodiols, and with a
      recombinant E. coli strain expressing the structural genes of naphthalene 1,2
      dioxgenase from Pseudomonas sp. NCIB 9816-4. 3-Hydroxycarbazole is presumed to
      result from the dehydration of an unstable cis-dihydrodiol.

PMID- 8270196
TI  - Growth and plasmid-encoded naphthalene catabolism of Pseudomonas putida in batch
      culture.
AB  - The growth characteristics of Pseudomonas putida plasmid-harbouring strains which
      catabolize naphthalene via various pathways in batch culture with naphthalene as
      the sole source of carbon and energy have been investigated. The strains under
      study were constructed using the host strain P. putida BS394 which contained
      various naphthalene degradation plasmids. The highest specific growth rate was
      ensured by the plasmids that control naphthalene catabolism through the meta
      pathway of catechol oxidation. The strains metabolizing catechol via the ortho
      pathway grew at a lower rate. The lowest growth rate was observed with strain
      BS291 harbouring plasmid pBS4 which controls naphthalene catabolism via the
      gentistic acid pathway. Various pathways of naphthalene catabolism appear to
      allow these strains to grow at various rates which should be taken into account
      when constructing efficient degraders of polycyclic aromatic compounds.

PMID- 8270197
TI  - Insertion sequence analysis of protoplast fused strains of Lactococcus lactis
      ssp. cremoris.
AB  - The use of insertion sequence probes for the analysis of fusants obtained
      following protoplast fusion is described. Hybridization of both total and plasmid
      DNA from parent and fusant strains with probes to IS904 and ISS1 showed that of
      the four protoplast fusions examined, three appeared to involve a rearrangement
      of genetic material while in the fourth the fusant appeared similar to one of the
      parental strains. This method of analysis provides more information about the
      changes induced by protoplast fusion than that obtained by monitoring the
      acquisition or loss of individual characteristics.

PMID- 8270198
TI  - Spontaneous mutation of Thiosphaera pantotropha enabling growth on methanol
      correlates with synthesis of a 26 kDa c-type cytochrome.
AB  - Thiosphaera pantotropha grows on methanol as carbon and energy source following
      spontaneous mutation to a Mox+ phenotype after incubation in media containing
      methanol. Acquisition of ability to grow on methanol correlates with the
      appearance of a c-type cytochrome, molecular mass 26 kDa, which is suggested to
      substitute for the product of the moxG gene, which is the electron acceptor from
      methanol in related bacteria, but which is absent from T. pantotropha. Mutation
      leading to growth on methylamine as carbon and energy source was not observed
      despite the presence of in vitro methylamine dehydrogenase activity in cells
      grown on choline. Lack of growth on methylamine may correlate with the absence of
      amicyanin, which is the obligatory electron acceptor from methylamine
      dehydrogenase in other organisms.

PMID- 8270199
TI  - Pleurotus fungi produce mevinolin, an inhibitor of HMG CoA reductase.
AB  - Fungi of the genus Pleurotus were shown to produce the 3-hydroxy-3-methylglutaryl
      CoA reductase inhibitor mevinolin. Crude methanol extracts and the purified
      inhibitor from three different species, P. sapidus, P. saca and P. ostreatus,
      were tested using the solubilized microsomal HMGCoA reductase from Chinese
      hamster ovary cells. The identity of the inhibitor was also confirmed by thin
      layer chromatography, high pressure liquid chromatography and mass spectroscopy.

PMID- 8270200
TI  - A study of homologous chromosomes using a morphometric approach.
AB  - A previous study of 100 karyotyped metaphase cells has demonstrated the utility
      of a graphic arts tool in deriving chromosome measurements for relative length
      determination. In the present study we utilize this same approach to address the
      question: "What are the average differences in relative lengths between
      apparently normal homologous chromosomes?" Normal standards derived from this
      study will be useful for testing specific hypotheses involving heteromorphic
      differences between homologs. No such data on normal controls could readily be
      found in either An International System for Human Cytogenetic Nomenclature (1985)
      or elsewhere.

PMID- 8270201
TI  - Evidence from a maize desynaptic mutant points to a probable role of synaptonemal
      complex central region components in provision for subsequent chiasma
      maintenance.
AB  - Homozygotes for the dsy1 desynaptic mutant of maize show massive failure of
      chiasma maintenance during diplotene and diakinesis. Although some chiasmata
      persist until anaphase I in most microsporocytes expressing this mutant,
      homozygotes are completely or nearly completely sterile, owing apparently to
      disjunctive irregularities. Pachytene synaptic errors and some synaptic failure
      also are found, but recombination nodules are common in homologously synapsed
      regions, and equational separation of a heterozygous knob into univalents or open
      arms at diakinesis clearly demonstrates that chiasma failure occurs following
      crossing-over. A wider than normal synaptonemal complex central region and
      uniform apparent weakness of central region cross connections to spreading
      procedures strongly suggest the presence of a genetic lesion in a synaptonemal
      complex central region component. The dsy1 mutant may provide an especially
      important source of material for molecular studies on the nature of chiasma
      maintenance mechanism.

PMID- 8270202
TI  - Molecular characterization and cytonuclear disequilibria of two Drosophila
      subobscura mitochondrial haplotypes.
AB  - According to restriction site analyses of mitochondrial DNA, Drosophila
      subobscura shows a polymorphism that consists of two frequent haplotypes that are
      evenly distributed all over the Old World and several rare haplotypes never
      present in more than one locality. To ascertain the causes responsible for such
      distribution, three different mtDNA fragments from haplotypes I and II sampled in
      a population from Zurich have been partially sequenced. Only three silent
      nucleotide changes have been detected in the ND5 gene. One of them implies the
      loss of the HaeIII restriction site, which differentiates haplotype I from
      haplotype II. On the basis of these results as well as on others involving the
      geographic distribution of haplotypes I and II, they can be considered
      phenotypically equivalent. The sequencing study has been complemented with the
      analysis of cytonuclear disequilibria between mitochondrial haplotypes and
      different nuclear loci in four D. subobscura populations. As expected, no
      significant cytonuclear disequilibria have been found between haplotypes I and
      II. Moreover, when haplotypes I and II were pooled and compared with the rare,
      endemic haplotypes similar results were obtained.

PMID- 8270203
TI  - The adenosine2 gene of Drosophila melanogaster encodes a formylglycineamide
      ribotide amidotransferase.
AB  - Drosophila melanogaster genomic DNA spanning an adenosine2 gene rearrangement
      breakpoint (in cytological map region 26B1-2) was cloned and a composite ade2
      base sequence was derived from this DNA and from a corresponding cDNA. Based on
      genetic evidence, the ade2 gene is thought to encode the purine biosynthetic
      enzyme formylglycineamide ribotide amidotransferase (FGARAT). The cDNA hybridizes
      to a 4.8-kb message that encodes a 1354 amino acid polypeptide with extensive
      similarity to Escherichia coli FGARAT. The D. melanogaster FGARAT amino acid
      sequence is considerably more like that of the E. coli enzyme than is the FGARAT
      of B. subtilis, which has two polypeptides with, collectively, 969 amino acids.
      It is suggested that the taxonomically anomalous similarity between the
      eukaryotic FGARAT and that from E. coli may indicate horizontal exchange of
      genetic material. On the basis of substantially greater conservation of sequences
      shared by all three species compared with those present only in E. coli and D.
      melanogaster, we suggest that no radical alteration of enzymatic function
      accompanied the transition between the single-gene and the two-gene state.

PMID- 8270204
TI  - Genetic variation in paw preference (handedness) in the mouse.
AB  - Lateralization of paw preference in laboratory mice in a single-paw reaching task
      has been used as a model system for left- and right-hand usage. Given a set
      number of paw reaches for food from a centrally placed food tube, an individual
      mouse will exhibit a reliable number of left and right paw reaches. Within any
      single inbred strain, there are approximately equal numbers of left-pawed and
      right-pawed mice. Nevertheless, significant strain differences have been reported
      for the degree of lateralization of paw preference. We report here a systematic
      survey of paw preference in 12 inbred strains of the mouse in which the degree of
      lateralization falls into two groups of weakly lateralized and highly lateralized
      paw preference. The genetic inference is that a single major gene may control
      some function, and alternate alleles at this locus are expressed as weakly and
      highly lateralized paw preference. Reciprocal crosses indicate the trait is
      additive with no maternal or X-linked effects. The direction of paw preference
      has previously appeared to be genetically neutral, but in some strains there is
      evidence of significant deviation of the numbers of mice to the left and right of
      equal paw usage, independent of degree of lateralization, and this suggests that
      direction of left-right paw usage may be a separate genetic trait in the mouse
      model.

PMID- 8270205
TI  - Clusters of interspersed repeated DNA sequences in the rice genome (Oryza).
AB  - We have characterized a repeated DNA sequence (RTL122) from rice (Oryza sativa
      L.) with respect to its organization in the rice genome and its distribution
      among rice and other plants. The results indicate that the RTL122 sequence is
      interspersed in the rice genome and limited to the genus Oryza. It is highly
      polymorphic and can be used to fingerprint rice varieties. A structure was
      observed in which several repeated sequences were clustered in DNA regions of 15
      20 kb. We characterized three bacteriophage lambda clones that contained the
      RTL122 sequence. Southern analysis using probes derived from restriction
      fragments of the three lambda clones indicated that all fragments except one are
      interspersed repeated sequences and belong to different repeated sequence
      families. Subsequent slot blot hybridization showed that most of them are only
      present within the genus Oryza. Some of the Oryza-specific, physically linked
      sequences show the same phylogenetic distribution, which suggests that these
      sequences might have evolved in a coordinate fashion. On the other hand, some of
      the repeated sequences have a different distribution even though they are
      physically adjacent in the genome. We speculate that such blocks of interspersed
      repeated sequences may serve as hotspots for rapid changes in the rice genome.

PMID- 8270206
TI  - Genetic relatedness among rabbiteye blueberry (Vaccinium ashei) cultivars
      determined by DNA amplification using single primers of arbitrary sequence.
AB  - Most improved cultivars of commercially important hexaploid rabbiteye blueberry
      were developed from only four native selections collected from the wild; thus,
      many cultivars are closely related by lineage. The consanguinity among major
      cultivars is a potential problem, as the rabbiteye blueberries are highly self
      incompatible natural outcrossers with potential inbreeding depression. We
      investigated the extent of genetic relatedness among 15 improved cultivars and
      four wild selections by the technique of random amplified polymorphic DNA, also
      referred to as arbitrarily primed polymerase chain reaction. Single
      decanucleotides of arbitrary sequence revealed polymorphism among cultivars and
      wild selections. Genetic distances were estimated based on the amount of band
      sharing. Cluster analysis of genetic distance estimates tended to group siblings
      with each other and with one or both parents. The average genetic distance
      between improved cultivars decreased relative to the four wild parental
      selections, which might indicate progression towards inbreeding. The significance
      of increased genetic relatedness among the improved cultivars of rabbiteye
      blueberry and the application of molecular methods in breeding and commercial
      cultivation is discussed.

PMID- 8270207
TI  - Characterization of minisatellite sequences from Oryza sativa.
AB  - Two DNA sequences were cloned from the genome of cultivated rice (Oryza sativa
      L.) by cross-hybridization with the human minisatellite sequence 33.6. The rice
      sequences consisted of tandem direct repeats, which showed significant similarity
      to the 33.6 consensus sequence. Profiles capable of distinguishing different rice
      cultivars were detected by cross-hybridization with a DNA probe amplified by the
      polymerase chain reaction from one of the rice minisatellite sequences.

PMID- 8270208
TI  - Fluorescence in situ hybridization of bovine Alu-like sequences to bovine and
      ovine chromosomes.
AB  - Fluorescence in situ hybridization procedures have been applied to study the
      distribution of Alu-like sequences on bovine and ovine chromosomes. Unlike in man
      and mouse, where the Alu sequences produced discrete R-like bands, a more diffuse
      distribution of Alu-like sequences was observed on both bovine and ovine
      chromosomes. Under the conditions used, banding patterns useful for chromosome
      identification were not detected.

PMID- 8270209
TI  - Basics of Millard rotation-advancement technique for repair of the unilateral
      cleft lip deformity.

PMID- 8270210
TI  - An overview of middle ear disease in cleft palate children.

PMID- 8270211
TI  - Furlow palatoplasty: double opposing Z-plasty.

PMID- 8270212
TI  - Triangular flap repair of the unilateral complete cleft lip.

PMID- 8270213
TI  - Lip adhesion.

PMID- 8270214
TI  - The extended Skoog technique for repair of the unilateral cleft lip and nose
      deformity.

PMID- 8270215
TI  - The use of a temporary oral prosthesis to treat speech in velopharyngeal
      incompetence.

PMID- 8270216
TI  - Cleft surgery in the Third World.

PMID- 8270217
TI  - Anesthesia for cleft lip and cleft palate patients.

PMID- 8270218
TI  - Perspectives on palatoplasty.

PMID- 8270219
TI  - Alveolar cleft bone grafts.

PMID- 8270220
TI  - [Biological process in patients having been impregnated through GIFT or IVF-ET.
      Clinical experience].
AB  - There were analyzed in a retrospective way the results of pre-retrieval hormonal
      levels as well as the number of retrieved oocytes, mature oocytes and transferred
      embryos in three groups of patients (2 GIFT, 1 IVF-ET) which achieved a
      pregnancy, and were matched with groups with no pregnancy. There were no
      statistically significant differences in most of the analyzed parameters, by the
      aforementioned we can suppose that pregnancy depends of endometrial quality and
      in this moment we are not able to modify it satisfactorily.

PMID- 8270221
TI  - [Comparative study of cryosurgery and hysterectomy in the treatment of cervical
      intraepithelial neoplasia].
AB  - The purpose of this study was to compare the results of conservative management
      with cryosurgery and with hysterectomy in different stages of NIC. The records of
      235 treated patients from 1984 to 1991, were reviewed; 140 patients were treated
      with cryosurgery and 95 with total hysterectomy. Cure rate was for stage I in 34
      patients (94.5); for stage II in 54 patients (98.2%), and for stage III in 46
      patients (93.9%). For hysterectomy in NIC I in 5 patients (100%); for NIC II in
      15 (100%), and for NIC III in 74 (98.66%). Statistical study with square Chi
      showed a not significant P which means that there is no difference in the results
      of Cure and No Cure in both procedures. It is concluded that intraepithelial
      cervical neoplasia may be managed with both procedures, provided that the
      established criteria for cryosurgery and hysterectomy, are followed.

PMID- 8270222
TI  - [Preeclampsia in pregnancy. Importance of reclassification].
AB  - It is difficult to determine the etiology of hypertension during pregnancy on the
      basis of clinical criteria alone. The purpose of the present study is to
      emphasize the impact of the postpartum reclassification of the hypertensive
      disorders in gestation. One hundred and fifty eight patients with an initial
      diagnosis of preeclampsia were prospectively studied. The follow-up included a
      reclassification of their hypertensive disorder at 4, 8 and 12 weeks postpartum.
      Such reclassification was based on renal function test and values of blood
      pressure. Among 158 patients, 118 had an initial diagnosis of preeclampsia during
      pregnancy, and only in 39 cases (33%) such diagnosis was confirmed postpartum. At
      the time of reclassification the rest of the patients belonged to the following
      conditions: gestational hypertension without proteinuria 35%, chronic
      hypertension 16%, nephropathy (7 with renal biopsy) 11%, and 4% with chronic
      hypertension and superimposed preeclampsia. There was no significative difference
      in perinatal morbidity between patients with chronic and gestational
      hypertension. A total of 10% of perinatal mortality rate was found. We concluded
      that the reclassification postpartum of the hypertensive disorders in pregnancy
      is essential to avoid errors in diagnosis and to establish adequate maternal and
      perinatal outcomes in future pregnancies.

PMID- 8270223
TI  - [Usefulness of two tests for rapid diagnosis of urinary infections in pregnancy].
AB  - Sixty pregnant women with symptoms of UTI, who assisted to the Emergency Room of
      the INPer, were submitted to urine culture and rapid urine tests for the
      detection of nitrites and leukocytes with the "Multistix 10 SG" (R) stripes. A
      control group was integrated of 20 pregnant women without symptoms of UTI
      submitted to the same methodology. In the first group, 34 urine cultures were
      reported as negative, 9 were as contaminated and 17 were positive. The
      sensitivity and specificity of the nitrite test was 94%. For the leukocyte test,
      the sensitivity was 64% and the specificity was 100%. In the control group, 13
      urine cultures were negative, two were contaminated and five were positive. In
      this group, the sensitivity of the nitrite test was 100% and the specificity was
      92%; while the sensitivity of the leukocyte test was 40% and the specificity was
      100%.

PMID- 8270224
TI  - [Bilateral tubal occlusion by postpartum mini-laparotomy under local anesthesia
      and sedation].
AB  - The first 1000 cases of tubal sterilization post-delivery by minilaparotomy with
      sedation and local anesthetic, were reviewed; these procedures were realized at
      the Hospital of Zona Francisco del Paso y Troncoso of the IMSS, in Mexico City,
      during the period comprehended between December 1990 and October 1991. The
      greatest group of cases by age corresponded to the period between 20 to 29 years
      in 52.3%. 65% of the women had 3 or 4 children alive. The range of the diastolic
      blood pressure was between 70-80 mmHg in 66.3%. 19.7% with a value of hemoglobin
      less than 10 g. 2.3% of the patients with 100-120 kgs. of weight. The
      contraceptive method used previously with greatest frequency was the DIU in
      40.6%. In all of the cases the indication was satisfied parenthood. In 100% of
      the cases the same drug was used for sedation, diazepam (oral) and chlorhydrate
      of nalbulfine, with simple lidocaine as a local anesthetic. Likewise in all the
      cases the Pomeroy technique was performed. The time between the childbirth and
      the surgery was less than 12 hours in 92.9% of the cases. And the time between
      the surgery and the recuperation reset was of 12-34 hours in 96%. In 0.8% of the
      cases the transoperatory complication of the surgery was the bleeding as a result
      of tearing of the mesosalpinx. The postoperatory complications after one week
      were the formation of hematoma and/or abscess at the site of the incision
      representing 0.5% of the cases. All these procedures are realized at a unit that
      was created especially for this kind of surgery and treatment.

PMID- 8270225
TI  - [Safety, efficacy and control of the menstrual cycle by a monophasic oral
      contraceptive containing 75 mcg of gestodene and 30 mcg of ethynyl estradiol].
AB  - Al oral monophasic contraceptive formulation containing gestodene (75 mcg) and
      ethynilestradiol (30 mcg) is evaluated concerning its safety, efficacy and cycle
      control. Sixty-seven healthy women were included, allowing a total of 574
      evaluable cycles. This formulation showed a high degree of efficacy, with no
      pregnancies after its utilization. Side affects were similar or lower to other
      reported with another hormonal contraceptive oral formulations. Hematologic,
      biochemical or urinary parameters were not altered. An acceptable menstrual
      pattern was maintained. In conclusion, this formulation constitutes an oral
      contraceptive with a high efficacy rate, a well degree of acceptability and with
      a side effects profile similar or lower than those produced by other oral
      contraceptives.

PMID- 8270226
TI  - [Correlation of serum prolactin and cortisol values with paroxysmal disorders of
      epileptic and non-epileptic origin and their clinical value].
AB  - In 95 patients (44 women and 51 men, aged 14 to 86 yrs., average 44.9 yrs.) the
      serum levels of prolactin, cortisol and uric acid were investigated 30, 60 and
      120 min after seizure-like events. There were 53 fits of epileptic aetiology
      (EE), mainly tonic-clonic, and 42 attacks of non-epileptic aetiology (NEE). The
      uric acid of the epileptic patients 30 min postictally revealed significantly
      higher ratings (p < 0.05) compared to the control group (n = 36), but not
      compared to the NEE group. Serum cortisol was significantly higher after all
      investigated disturbances without differences in the EE and NEE group. After
      epileptic and non-epileptic attacks prolactin was significantly (p < 0.05)
      elevated in comparison to the baseline. The increase of 3 times the amount of the
      individual baseline and at the same time exceeding the range of reference were
      found in 73% of the epileptic and only in 7% of the non-epileptic patients. As
      hypothesis to the postictal prolactin rise we discuss disturbances in the
      neurotransmitter equilibrium within the hypothalamic-hypophyseal axis. We regard
      prolactin as a biochemical marker, which is a valuable aid in the differential
      diagnosis of epileptic and non-epileptic fits.

PMID- 8270227
TI  - [Sympathetic skin response--physiologic principles, normal values and clinical
      use].
AB  - Sympathetic skin reflex (SSR) was evaluated in the lower extremities of 60 normal
      volunteers aged 17 to 72 (mean age 38 +/- 16 years, 28 females, 32 males). SSR
      was obtainable in all volunteers and most often consisted of a biphasic wave with
      initial negative deflection. Mean latency was 2.16 +/- 0.20 s. Mean variation in
      a second repetitive measurement was 0.21 +/- 0.14 s. The SSR was not age- or sex
      dependent. There was a weak positive correlation of the SSR with the height of
      the volunteers (r = 0.271; p = 0.037). SSR was investigated in 39 patients with
      polyneuropathy (age 59 +/- 18). SSR was pathological in 51% on one or both legs.
      There was no correlation of the SSR to the aetiology nor to the type of lesion
      (axonal versus demyelinating polyneuropathy) nor to clinical symptoms. The
      applicability of the SSR is reviewed from the literature regarding
      polyneuropathy, erectile dysfunction, central degenerative diseases, multiple
      sclerosis, sympathetic reflex dystrophies, spinal and peripheral nerve lesions.
      SSR is briefly compared to alternative methods. SSR appears to be a reasonable
      method to describe a small section of the autonomic nervous system (sympathetic
      sudomotor function) and to calculate group differences. There appears to be no
      close correlation to any of the autonomic disturbances in individual patients.

PMID- 8270228
TI  - [SUNCT syndrome--case report and review of the literature].
AB  - The SUNCT syndrome is a recently described headache disorder characterised by
      shortlasting, unilateral headache attacks with conjunctival injection and
      tearing. Our report presents a further case and compares the findings in our
      patient with those in the cases described earlier. In addition, we review the
      literature and discuss possible aetiological and pathogenetic factors as well as
      the differential diagnosis of SUNCT syndrome, trigeminal neuralgia and cluster
      headache syndromes.

PMID- 8270229
TI  - What constitutes curative pancreatectomy for adenocarcinoma of the pancreas?
AB  - This is a review of the recent advances in radical pancreatectomy for
      adenocarcinoma of the pancreas. Over the last three decades, the operative
      mortality rate has decreased sharply to below 5%. On the basis of the
      clinicopathological evidence of the extent of the cancer, extended pancreatectomy
      with lymphatic and connective tissue clearance, in place of the traditional
      Whipple's procedure or total pancreatectomy is increasingly justified. In fact,
      use of this procedure has markedly reduced locoregional recurrence, and has
      improved the 5-year survival rate of pancreatic adenocarcinoma patients to more
      than 25%. However, such a beneficial effect is limited to those with less
      advanced cancer, for example, that in which the main tumor is 4 cm or less in
      diameter, nodal involvement is limited to the peripancreatic groups, and portal
      vein invasion is slight or absent. Future efforts should be aimed at developing
      adjuvant therapy that is equally as effective in reducing both locoregional
      recurrence and liver metastasis.

PMID- 8270230
TI  - Isolated pancreatectomy for pancreatic head carcinoma using catheter bypass of
      the portal vein.
AB  - We investigated perioperative complications and survival rate in 114 patients
      with pancreatic cancer who underwent surgical resection between July, 1981 and
      March, 1992 with an antithrombogenic bypass catheter of the portal vein which we
      have developed. With this catheter, mesenteric venous blood can be bypassed to
      the systemic circulation or intrahepatic portal vein to prevent portal congestion
      or hepatic ischemia during portal obstruction or simultaneous obstruction of the
      hepatic artery. All the arteries supplying, and veins draining, the pancreas are
      dissected prior to its manipulation, following which isolated pancreatectomy
      accompanied by portal vein resection can be performed. Eighty patients (70%) also
      underwent isolated pancreatectomy. The perioperative death rate was 9.6%, and the
      main factor contributing to mortality with the bypass method was not portal vein
      resection, but various postoperative complications, such as insufficiency of the
      pancreatojejunostomy and thrombosis of the hepatic artery or superior mesenteric
      artery after resection and reconstruction. We conclude that aggressive surgery
      with the bypass method increases the operability of pancreatic cancer, although
      auxiliary therapies combined with radical surgery are necessary to improve the
      therapeutic outcome for this cancer.

PMID- 8270231
TI  - Peritoneal metastases in pancreatic carcinoma.
AB  - Peritoneal metastases are present in about 50% of patients with pancreatic cancer
      at the time of death, and are the second most common site of involvement,
      following the liver. The small size of peritoneal metastases precludes their
      identification by CT scan, and thus they have to be identified by direct
      visualization, either at laparotomy or through laparoscopy. Adding laparoscopy to
      the staging protocol permits pre-operative identification of patients who will
      not benefit from surgery. Malignant cells are also found within the peritoneal
      cavity in 20 to 30% of patients with pancreatic cancer who otherwise have no
      peritoneal or liver metastases. Their presence, documented by peritoneal washings
      during laparoscopy or at the time of surgery, seems to be associated with an
      adverse prognosis.

PMID- 8270232
TI  - Current approaches to multimodality management of advanced pancreatic cancer.
AB  - For patients with localized pancreatic adenocarcinoma, the combination of
      radiation therapy and 5-fluorouracil has been shown to enhance patient survival.
      Following pancreatectomy, results in a second group of patients confirmed the
      benefit of 40 Gy of radiation administered as a split course, combined with 5
      fluorouracil during and following the radiation therapy, as noted in the original
      randomized study of the Gastrointestinal Tumor Study Group. When the disease is
      locally unresectable, 60 Gy of radiation administered in a double split regimen,
      in combination with 5-fluorouracil, has significantly prolonged survival. Split
      courses of radiation therapy seem better tolerated, allowing a greater proportion
      of patients to complete this phase of treatment. Hyperfractionation, heavy ion
      irradiation and intraoperative radiation therapy have not been found to be more
      beneficial. Newer approaches include continuous intravenous or intraarterial
      infusion of the 5-fluorouracil, addition of mitomycin C or cisplatin. The results
      of neoadjuvant trials of radiation and chemotherapy are not sufficiently mature
      to determine their effect on patient survival. Neoadjuvant therapy has not been
      subjected to testing in randomized trials. Chemotherapy will continue to offer
      very limited benefit for patients with advanced metastatic disease until more
      effective drugs can be developed. Innovative approaches utilizing growth factors
      and photodynamic therapy should be studied in carefully monitored fashion.

PMID- 8270233
TI  - Surgical resection of potentially curable pancreatic cancer with improved
      preservation of endocrine function--further evaluation of intraoperative
      cytodiagnosis.
AB  - Very early detection of pancreas cancer is most desirable, since it permits less
      invasive surgery which has a correspondingly greater chance of success. The
      present study investigated both surgical outcome and postsurgical quality of life
      in 8 patients whose occult neoplasms were successfully treated. In all 8
      patients, cytology of the pancreatic secretion obtained during endoscopic
      retrograde pancreatography (ERP) was positive, although no pancreatic tumor was
      detected by ERP, other examinations or intraoperative inspection. In these 8
      patients, our method of intraoperative cytodiagnosis to locate occult neoplasms
      of the pancreas (Surgery 1992; 111: 294-300) was used (1). Using this method of
      cytodiagnosis, we were able to avoid total pancreatectomy in 6 patients (75%; 3
      pancreatoduodenectomies and 3 caudal pancreatectomies), but not in the other 2
      patients. Histopathological study of the resected specimens indicated that the
      extent of pancreatic resection was quite appropriate in all 8 patients. There
      were 6 minimally invasive carcinomas, one carcinoma in situ and one borderline
      lesion. Neither nodal involvement nor severe invasion was found on microscopic
      inspection, and all have been disease-free for 23 +/- 13 months after surgery. In
      the 6 patients with partial pancreatectomies, both postoperative quality of life
      and general health were good, with no insulin-dependent diabetes developing.
      Thus, our cytology-guided surgical technique is very useful not only for locating
      occult and potentially curable neoplasms, but also for avoiding blind resection
      of the entire pancreas, permitting better preservation of pancreatic endocrine
      function.

PMID- 8270234
TI  - A clinical study on lymphatic flow in carcinoma of the pancreatic head area-
      peripancreatic regional lymph node grouping.
AB  - A detailed evaluation of the involvement of regional lymph nodes in 33 patients
      with cancer in the pancreas, distal common bile duct and papilla of Vater was
      undertaken with the aim of delineating the patterns of lymphatic spread of the
      tumor. Regional lymph nodes were involved in 91.7% of patients with pancreatic
      carcinoma, 62.5% of those with carcinoma of the distal common bile duct, and
      58.3% of those with carcinoma of the papilla of Vater. The neck of the pancreas
      appeared to be an "entrepot" through which cancer cells pass on their way to the
      lymph nodes. Other outstanding routes of spread include a route via the nodes
      situated around the superior mesenteric artery, a perineural route passing
      through the pancreatic plexus, and metastasis to the nodes along the abdominal
      aorta. Grouping of the involved lymph nodes is discussed and a new grouping is
      proposed with reference to the literature.

PMID- 8270235
TI  - Effect of prostaglandin E2 on cellular, lysosomal and mitochondrial fragility in
      caerulein-induced pancreatitis in rats.
AB  - The effects of prostaglandin E2 on the fragility of cellular and subcellular
      organelles in caerulein-induced acute pancreatitis were investigated in rats.
      PGE2 at doses of 50 and 100 micrograms/kg/hr infused for 2 hours before and
      during caerulein (5 micrograms/kg/hr for 3.5 hours) infusion significantly
      prevented the increased discharge of both amylase and lactate dehydrogenase from
      dispersed acini, and the leakage of cathepsin B from lysosomes and of malate
      dehydrogenase from mitochondria in the subcellular fraction in vitro. These
      results suggest that PGE2 has a cytoprotective effect against caerulein-induced
      pancreatitis by stabilizing cell and lysosomal and mitochondrial membranes.

PMID- 8270236
TI  - Prognosis after early onset of ulcerative colitis. A study from an unselected
      patient population.
AB  - All patients with onset of ulcerative colitis before the age of 20 years from a
      population of 65,000 inhabitants were studied. The study period was 30 years
      (1961 through 1990). There were 32 patients, 18 male and 14 female, giving an
      incidence of 0.7 patients/100,000/year. Twenty-four patients had total colitis
      and 8 had limited disease. The observed duration of the disease was 0-30 (mean
      18, median 20) years. One patient died of fulminant disease. No colorectal
      carcinoma was diagnosed. In 7 patients, low-grade dysplasia was diagnosed, which
      did not progress during an observation period of 2-10 years. DNA aneuploidy was
      detected in 6 patients. Seven patients (22%) were operated on after a disease
      duration of 0-10 (mean 4, median 3) years on clinical grounds. No cancer
      prophylactic colectomy was performed. It is concluded that, in an unselected
      population of patients with early onset of ulcerative colitis, mortality and
      cancer risk are low. The need for operative treatment during the first 15 years
      of the disease was around 22 per cent. Endoscopic surveillance was given
      preference over prophylactic colectomy in patients with low-activity or quiescent
      disease.

PMID- 8270237
TI  - A study of the lactic dehydrogenase isoenzyme patterns in the adenoma--carcinoma
      sequence of the colon.
AB  - In order to determine whether the LDH isoenzyme pattern, measuring the
      percentages of LDH4-5 (M monomer), might be a marker in the adenoma-carcinoma
      sequence, 103 adenomas, 8 adenomas with proven malignant degeneration and 27
      adenocarcinomas of the large intestine, as well as 12 biopsy samples of colonic
      mucosa from normal controls, were studied histologically and histochemically. The
      proportion of M polypeptide was significantly increased in adenomas of larger
      size (diameter > 2 cm), in adenomas with a larger villous component, and in those
      with severe dysplasia. The largest proportion of M polypeptide was found in
      villous adenomas and colloid adenocarcinomas, and might reflect a common origin.
      These results suggest that the histochemical study of the LDH isoenzymogram might
      be a useful marker for detecting early malignant degeneration in adenomas of the
      colon.

PMID- 8270238
TI  - Small polyps found at sigmoidoscopy: are they significant?
AB  - In this study we prospectively examined the significance of small polyps found at
      screening flexible sigmoidoscopy and studied in particular, the possibility that
      hyperplastic polyps in the rectosigmoid can serve as potential markers for
      neoplastic polyps proximal to this area. During the last three years we performed
      sigmoidoscopy on 1500 patients. One hundred and five patients (7%) had one or
      more polyps in the rectosigmoid. Exclusion criteria were polyps of > 1 cm in
      size, a history of bleeding, inflammatory bowel disease or past polypectomy.
      After excluding 30 patients, 75/1500 (5%) patients with small polyps remained in
      the study. All these patients were submitted to total colonoscopy with removal of
      all polyps found. Histopathology showed that 45/75 (60%) patients had
      hyperplastic polyps and 30/75 (40%) had at least one adenomatous polyp. Among the
      45 patients with hyperplastic polyps at flexible sigmoidoscopy, 16 (35.5%) had a
      more proximal adenomatous polyp. Nine of the 30 patients (30%) who had at least
      one adenomatous polyp in the rectosigmoid were found to have them more
      proximally. We conclude that a) size alone is not an accurate predictor of the
      histology of the polyp, b) because small polyps, either hyperplastic or
      adenomatous, in the rectosigmoid indicate a risk for adenomatous polyps more
      proximally, all patients with small polyps found during flexible sigmoidoscopy
      should be submitted to total colonoscopy.

PMID- 8270239
TI  - Frequency of gastroesophageal reflux in patients with liver cirrhosis.
AB  - Twenty-five adult patients with liver cirrhosis, and another 30 patients with no
      liver disease but referred with symptoms suggestive of gastroesophageal reflux
      disease were selected at random. Twenty-four hour ambulatory intra-esophageal pH
      measurement and upper gastrointestinal endoscopy were carried out on all patients
      recruited. Applying the former test, 16 (64%) of the patients with liver
      cirrhosis have gastroesophageal reflux disease. This figure is comparable with
      the 70% (21/30) rate recorded in the group of dyspeptic patients clinically
      thought to have the disorder. A positive endoscopic diagnosis was much lower at
      12% and 23%, respectively. No significant differences were observed among liver
      disease patients when they were subdivided in accordance with the etiology of
      liver cirrhosis and the grade of esophageal varices. We conclude that
      gastroesophageal reflux disease occurs at a high frequency (64%) in patients with
      liver cirrhosis and portal hypertension, irrespective of the etiology of
      cirrhosis and the grade of esophageal varices. It is therefore considered to be
      the main cause of esophagitis in these patients, and that it might play a role in
      initiating a variceal bleeding episode. The latter hypothesis needs further
      evaluation.

PMID- 8270240
TI  - The impact of low-residue enteral feeding on the healing of colonic anastomoses.
AB  - This study was carried out with the aim of comparing colonic anastomosis
      cicatrization in rats fed either standard rat chow or a low-residue enteral diet.
      Energy intake, the evolution of body weight, fecal weight, macroscopic and
      microscopic evaluation of the anastomoses, anastomotic bursting pressure, and
      collagen concentration in the anastomotic tissue were all evaluated. Anastomotic
      complications were more common among the animals fed standard rat chow, and
      cicatrization was more inflammatory than in the rats given a low-residue enteral
      diet. Although the latter was more effective in preventing anastomotic
      complications, it resulted in a lower gain in collagen and hence a diminished
      resistance to the increase in intraluminal pressure associated with the
      administration of such diets. Colonic contents, including the fecal bolus and
      bacteria, may be held responsible for the increased number of complications, the
      augmentation of collagen content, and the improvement in the resistance to
      intraluminal pressure.

PMID- 8270241
TI  - Endoscopic and clinicopathological features of primary gastric lymphoma.
AB  - Thirty-three patients with primary gastric lymphoma over a period of 32 years
      were studied. Endoscopic findings indicated that there were many cases of
      multiple lymphoma in the stomach, or with extensive tumor-infiltration, and that
      it was necessary to carefully inspect the entire stomach to determine the scope
      of resection and improve diagnostic accuracy. It is also particularly important
      not to damage the tissue during biopsy and to take deep large specimens from the
      ulcer margin, surrounding wall, and area of erosion. As compared
      clinicopathologically with gastric carcinoma, primary gastric lymphoma is found
      more frequently in younger females, with invasion of the entire stomach and
      extensive lymph node infiltration. By performing adequate resection of lymph
      nodes, as is done for gastric carcinoma, and administering appropriate
      combination chemotherapy, postoperative longterm results were similar to, or
      better than, those obtained with gastric carcinoma.

PMID- 8270242
TI  - Stemline heterogeneity of nuclear DNA in hepatocellular carcinoma.
AB  - Flow cytometric analysis of intratumoral DNA stemline heterogeneity was carried
      out in 48 patients who underwent liver resection for hepatocellular carcinoma
      (HCC). The nuclear DNA content was determined in specimens cut into one
      centimeter square pieces; all specimens had been taken from the largest section
      of the tumor. Of the 48 tumors twelve (25%) were diploid (group D), 11 (22.9%)
      had both diploid and aneuploid patterns (group DA), and the remaining 25 (52.1%)
      were aneuploid (group A). Out of 25 group A tumors, eleven had two or more
      different aneuploid peaks (multiple aneuploid). Thus, DNA stemline heterogeneity
      was present in 22 tumors (45.7%). With respect to survival, patients with group A
      tumors had a significantly poorer prognosis than did those with group D tumors,
      irrespective of tumor size. In group DA patients, the outcome was influenced by
      the "poor" prognostic nature of the positive DNA aneuploidy. Thus, HCC has a
      higher incidence of intratumoral DNA heterogeneity than previously considered,
      and the prognosis for patients with a positive aneuploidy pattern is poor.

PMID- 8270243
TI  - Liver abscess after percutaneous ethanol injection (PEI) therapy for
      hepatocellular carcinoma. A case report.
AB  - We present a case of liver abscess after percutaneous ethanol injection (PEI)
      therapy for the treatment of recurrent hepatocellular carcinoma (HCC). The 56
      year-old woman had a past history of cholecystoduodenostomy for cogenital
      dilatation of the bile duct, and pneumobilia was observed in the intrahepatic
      bile ducts prior to PEI. The abscess was successfully treated by percutaneous
      abscess drainage and antibiotic therapy. Klebsiella pneumonia, one of the most
      common causative organisms of biliary tract infection, was isolated from the
      abscess. Thus, biliary tract infection related to the previous biliary-enteric
      anastomosis operation may have been one of the causative factors in the liver
      abscess in this patient. The rare experience reported here suggests that a
      careful search for coexistent abscess at the time of PEI is important in HCC
      patients with biliary-enteric anastomosis, especially in those with pneumobilia.

PMID- 8270244
TI  - Mixed types of chronic active hepatitis and primary biliary cirrhosis associated
      with the anti-phospholipid antibody syndrome: a case report.
AB  - An understanding of the pathogenesis of mixed types of chronic active hepatitis
      and primary biliary cirrhosis is important for the treatment of the patients. A
      40-year-old Japanese woman with antiphospholipid syndrome has been treated with
      prednisolone for two years since she was diagnosed as having a mixed type of
      chronic active hepatitis and primary biliary cirrhosis. Biochemical tests for
      liver function were normal during treatment. Laparoscopy revealed a white liver,
      and histology demonstrated disappearance of the findings of piecemeal necrosis or
      chronic nonsuppurative destructive cholangitis in the specimen. Steroid treatment
      of patients with mixed types of chronic active hepatitis and primary biliary
      cirrhosis is controversial, since it is contra-indicated in some. Although the
      clinical features of the patients varies from one to another, this case suggests
      that the autoimmune mechanism of some patients may resemble autoimmune hepatitis
      rather than primary biliary cirrhosis, and treatment with steroid is effective.

PMID- 8270245
TI  - Echo-guided percutaneous ethanol injection in small hepatocellular carcinoma:
      personal experience.
AB  - We performed echo-guided percutaneous ethanol injection of the lesion in 26
      cirrhotic patients with 33 hepatocellular carcinomas measuring 3 cm in diameter
      or less. Post-treatment lesions had disappeared in 4 patients, while in the
      remaining 22 patients the echo pattern of the lesion had changed and biopsies
      were negative. Fifteen patients (follow-up 11-30 months) remain disease-free,
      while recurrence occurred between 3 and 36 months in 7 cases. Percutaneous
      ethanol injection was successfully repeated in 4 cases; 5 patients died, 1 of
      HCC, 2 of esophageal variceal bleeding, and 2 of liver failure; 3 of the last
      four patients had Child's C disease. Percutaneous ethanol injection is a valuable
      treatment for hepatocellular carcinomas measuring not more than 3 cm. It has yet
      to be established how far this treatment influences the survival rates of
      patients and the natural course of hepatocellular carcinoma.

PMID- 8270246
TI  - Mesothelial cyst complicated by torsion: preoperative imaging evaluation.
AB  - The diagnosis mesothelial cyst is infrequently made pre-operatively, because of
      the relative rarity of this lesion as a cause of distinct abdominal complaints
      and a lack of definitive diagnostic tests. A case of a mesothelial cyst
      complicated by ileal torsion evaluated preoperatively by various imaging
      modalities, including plain radiographs, ultrasound, computed tomography and
      enteroclysis studies is presented. It was shown that appearances on enteroclysis
      significant aided the differential diagnosis, by preoperatively defining the
      cause of clinical presentation and the extent and degree of the intestinal
      involvement.

PMID- 8270247
TI  - Ordering markers in the region of the ataxia-telangiectasia gene (11q22-q23) by
      fluorescence in situ hybridization (FISH) to interphase nuclei.
AB  - Fluorescence in situ hybridization (FISH) to interphase nuclei was performed to
      order probes corresponding to bands 11q22-q23 where the ataxia-telangiectasia
      (AT) gene(s) have been located. Cosmid probes and one phage probe previously
      localized to this chromosome 11 region by FISH to metaphase chromosomes, were
      hybridized to interphase nuclei of the somatic cell hybrid J1a, which contains
      chromosome 11 as the only human chromosome. Two-color FISH was used with a
      centromeric reference probe marker. The following order was obtained: cen-D11S385
      (CJ52.75)-CJ52.3-D11S384 (CJ52.193)-CJ52.114-D11S424 (CJ52.77)-D11S132-NCAM
      D11S351 (CJ52.208)-tel. The validity of using the centromeric probe was
      illustrated by showing that a probe corresponding to 11p13 hybridized more
      closely to the centromere than a probe corresponding to 11q22-q23, and by using
      cosmids hybridized three by three.

PMID- 8270248
TI  - Human high-affinity Fc gamma RI (CD64) gene mapped to chromosome 1q21.2-q21.3 by
      fluorescence in situ hybridization.
AB  - The human Fc gamma RI gene encodes for a high-affinity Fc gamma receptor that
      plays pivotal roles in the immune response. We have used fluorescence in situ
      hybridization analysis to localize the Fc gamma RI gene to human chromosome 1.
      The human Fc gamma RI (CD64) gene has been assigned to human chromosome 1q21.2
      q21.3 using R-banded human (pro)metaphase chromosomes.

PMID- 8270249
TI  - Quantification of point mutations associated with Leber hereditary optic
      neuroretinopathy by solid-phase minisequencing.
AB  - About two-thirds of patients with Leber hereditary optic neuroretinopathy (LHON)
      harbor mutations in mitochondrial DNA at positions 11778 (ND4) or 3460 (ND1).
      Thus, the clinical diagnosis of LHON can often be confirmed with mutation
      analysis. Detection of pathogenic mutations and quantification of heteroplasmy
      has mainly relied on PCR and restriction site analysis and densitometric
      scanning. We applied the recently developed solid-phase minisequencing method,
      based on primer-guided nucleotide incorporation, to the simultaneous detection
      and quantitation of the ND4/11778 and ND1/3460 mutations. The method was highly
      sensitive, heteroplasmy as low as 1.5% being easily detected. Rapid,
      reproducible, and accurate results prove solid-phase minisequencing to be the
      method of choice for quantitative analysis of LHON mutations.

PMID- 8270250
TI  - A human gene that restores the DNA-repair defect in SCID mice is located on
      8p11.1-->q11.1.
AB  - In order to map the gene that is responsible for the DNA-repair defect in severe
      combined immune deficient (SCID) mice, a mixture of microcells independently
      isolated from mouse A9 cells containing pSV2neo-tagged human chromosomes 5, 7, 8,
      9, 11, 15, 18 or 20 were fused with SCID fibroblast cell lines SCVA2 and SCVA4,
      which were originally established from lung tissue of the C.B.17-scid/scid mouse
      by SV40 virus transfection. After irradiation with 60Co gamma-rays and selection
      with antibiotic G418, 12 independent clones were obtained, of which 4 contained
      an intact chromosome 8, 3 clones contained a deleted chromosome 8 [del(8)q22-
      >qter or del(8)q23--> qter] and remaining 5 had no detectable or specific human
      chromosome. We further independently transferred a single human chromosome 8 or
      11 into the SCVA cells via microcell fusion, and examined the radiation
      sensitivity of the microcell hybrids. Complementation of the radiation
      sensitivity was correlated with the presence of human chromosome 8 in microcell
      hybrids, whereas no correlation was observed in clones following the transfer of
      human chromosome 11. Thus, the results indicate that human chromosome 8 restored
      high sensitivity to ionizing radiation. A number of subclones that were radiation
      resistant or sensitive were isolated from the microcell hybrids. The concordance
      of the radiation sensitivity with the presence or absence of specific DNA
      fragments on chromosome 8 indicates that the human gene is located on the
      centromeric region of chromosome 8, i.e., 8p11.1--> q11.1.

PMID- 8270251
TI  - Genetic analysis of the catalytic domain of the GAP gene in human lung cancer
      cell lines.
AB  - Cell lines of non-small cell lung cancer (non-SCLC) have been shown to contain
      activating mutation of the K-ras oncogene in about 30% of cases, whereas no small
      cell lung cancer (SCLC) cell lines displayed these mutations. Biochemically,
      these mutations result in the ras gene product (p21) being constitutively
      activated in its GTP-bound form and insensitive to the hydrolytic action of the
      ras-specific GTPase-activating protein (ras GAP). We hypothesized that, if tumor
      development is related to the p21 ras being in the active GTP-bound state, then a
      similar malignant phenotype may result from an inactivating mutation in the ras
      GAP gene in the region that interacts with ras p21 (so-called catalytic domain).
      To test this hypothesis, we screened a panel of SCLC and non-SCLC cell lines for
      major genetic alterations in the catalytic domain of the GAP gene with the
      Southern blot technique, and for minor genetic abnormalities (e.g., point
      mutations) with denaturing gradient gel electrophoresis and single-strand
      conformation polymorphism. Mutations in the catalytic domain of the GAP gene
      could not be demonstrated by any technique in any cell line examined. We conclude
      that mutational inactivation of the catalytic domain of the GAP gene probably
      does not contribute to the development of lung cancer.

PMID- 8270252
TI  - Achievement of meiosis in XXY germ cells: study of 543 sperm karyotypes from an
      XY/XXY mosaic patient.
AB  - Human sperm chromosomes from a 46,XY/47,XXY male were obtained using the
      technique of in vitro penetration of zona-free hamster eggs. The analysis of 543
      sperm complements shows a significantly increased incidence (0.9%) of
      hyperhaploid gonosomal 24,XY sets, with a lack of the expected corresponding
      gonosomal hypohaploidies, and a normal rate of autosomal non-disjunctions. These
      results support the suggestion that 47,XXY cells are able to go through meiosis
      and to form spermatozoa. Only 24,XY sperm chromosomal constitutions were observed
      suggesting a preferential pairing of homologous sex chromosomes in 47,XXY
      spermatocytes.

PMID- 8270253
TI  - Presence of an expressed beta-tubulin gene (TUBB) in the HLA class I region may
      provide the genetic basis for HLA-linked microtubule dysfunction.
AB  - An expressed beta-tubulin gene (TUBB) has previously been localized to chromosome
      region 6pter-p21 in man. By using a panel of deletion mutant cell lines and
      radiation-reduced hybrids containing fragments of chromosome 6, the TUBB locus
      could be mapped to the HLA class I region at 6p21.3. A long range restriction map
      including TUBB and several HLA class I genes was then generated by rotating field
      gel electrophoresis. The results show that TUBB maps to a segment 170-370 kb
      telomeric of HLA-C. This location suggests that a mutation at the TUBB locus
      could be the cause for certain forms of HLA-linked microtubule dysfunction,
      including immotile cilia syndrome.

PMID- 8270254
TI  - Detection of eleven mutations causing acute intermittent porphyria using
      denaturing gradient gel electrophoresis.
AB  - Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized
      by mutations of the gene coding for porphobilinogen deaminase (PBGD). Until now,
      sixteen different mutations have been described. In an effort to investigate
      further the molecular epidemiology of AIP, we have undertaken a systematic study
      of different exons of the PBGD gene from a large number of unrelated patients.
      Here, we have examined seven of the fifteen exons of the gene from 43 unrelated
      Dutch and French AIP patients using denaturing gradient gel electrophoresis after
      polymerase chain reaction amplification. Eleven new mutations were found,
      accounting for the enzymatic defect in about half of the patients. This study
      further documents the molecular heterogeneity of the mutations responsible for
      AIP and describes an efficient strategy to detect the mutations in patients with
      previously unknown abnormalities.

PMID- 8270255
TI  - Molecular genetic investigations of the mechanism of tumourigenesis in von Hippel
      Lindau disease: analysis of allele loss in VHL tumours.
AB  - Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer
      syndrome characterised by the development of retinal and central nervous system
      haemangioblastomas, renal cell carcinoma (RCC), phaeochromocytoma and pancreatic
      tumours. The VHL disease gene maps to chromosome 3p25-p26. To investigate the
      mechanism of tumourigenesis in VHL disease, we analysed 24 paired blood/tumour
      DNA samples from 20 VHL patients for allele loss on chromosome 3p and in the
      region of tumour suppressor genes on chromosomes 5, 11, 13, 17 and 22. Nine out
      of 24 tumours showed loss of heterozygosity (LOH) at at least one locus on
      chromosome 3p and in each case the LOH included the region to which the VHL gene
      has been mapped. Chromosome 3p allele loss was found in four tumour types (RCC,
      haemangioblastoma, phaeochromocytoma and pancreatic tumour) suggesting a common
      mechanism of tumourigenesis in all types of tumour in VHL disease. The smallest
      region of overlap was between D3S1038 and D3S18, a region that corresponds to the
      target region for the VHL gene from genetic linkage studies. The parental origin
      of the chromosome 3p25-p26 allele loss could be determined in seven tumours from
      seven familial cases; in each tumour, the allele lost had been inherited from the
      unaffected parent. Our results suggest that the VHL disease gene functions as a
      recessive tumour suppressor gene and that inactivation of both alleles of the VHL
      gene is the critical event in the pathogenesis of VHL neoplasms. Four VHL tumours
      showed LOH on other chromosomes (5q21, 13q, 17q) indicating that homozygous VHL
      gene mutations may be required but may not be sufficient for tumourigenesis in
      VHL disease.

PMID- 8270256
TI  - Two new mutations in the porphobilinogen deaminase gene and a screening method
      using PCR amplification of specific alleles.
AB  - Acute intermittent porphyria (AIP) is attributable to defects in the
      porphobilinogen deaminase (PBGD) gene. Two new mutations have been found in the
      PBGD gene in Swedish families. The first is a G to A splice mutation in the last
      position of intron 9. A screening method using allele-specific amplification has
      been designed for the rapid detection of this mutation. The second mutation is a
      C to T substitution in exon 10, changing Arg201 to Trp. This mutation can be
      detected by restriction enzyme cleavage.

PMID- 8270257
TI  - Isolation and characterization of the human genomic locus coding for the putative
      metastasis control gene nm23-H1.
AB  - Nm23-H1 gene expression is inversely correlated with tumor metastatic potential
      in certain tumors, including melanomas, breast carcinomas, and hepatocellular
      carcinomas. Using nm23-H1 c-DNA primer and genomic polymerase chain reaction
      (PCR) amplification, we purified three PCR fragments (one of 4kb and two of 2 kb)
      covering the whole human genomic locus of the gene (8.460bp). We recombined the
      PCR products into pUC18 and produced a restriction map to perform subcloning.
      Complete sequencing of genomic PCR fragments, including the whole coding region
      of nm23-H1, revealed that the gene consists of five exons and four introns
      spanning 8.5kb. A sequence homology analysis between human nm23-H1 and the
      homolog gene of the rat (NDP-K beta) shows that exon-intron boundaries are well
      conserved between these two species.

PMID- 8270258
TI  - Incidence of chromosome 3, 7, 10, 11, 17 and X disomy in mature human sperm
      nuclei as determined by nonradioactive in situ hybridization.
AB  - In situ hybridizations were performed on mature human sperm cells with biotin
      labeled alpha-satellite DNA probes specific for chromosomes 3, 7, 10, 11, 17, and
      X in order to reveal the disomy rate for each of these chromosomes. A total of
      76,253 sperm nuclei from seven healthy probands aged 23-57 years were analyzed.
      An average of 12,000 sperm nuclei (at least 1500 per donor) showing hybridization
      were scored with each probe. The disomy rate as indicated by two distinct
      hybridization signals turned out to be similar for all chromosomes, ranging from
      0.31% to 0.34%. There were no significant interindividual differences and no age
      correlation in the frequency of disomic sperm cells between the donors.

PMID- 8270259
TI  - Population screening of lactate dehydrogenase deficiencies in Fukuoka Prefecture
      in Japan and molecular characterization of three independent mutations in the
      lactate dehydrogenase-B(H) gene.
AB  - Screening for lactate dehydrogenase (LDH) subunit deficiencies was performed on
      2880 blood samples from healthy individuals in the Fukuoka Prefecture in Japan by
      means of electrophoresis. The frequencies of heterozygotes with either LDH-A or
      LDH-B deficiency were found to be 0.104% at each locus. These estimated
      frequencies of either LDH-A or LDH-B deficiencies were slightly lower than, but
      not significantly different from, those found previously in Shizuoka Prefecture.
      The genetic mutations in individuals heterozygous for LDH-B deficiency were
      analyzed by the polymerase chain reaction and DNA conformation polymorphism.
      Abnormal migration patterns were observed in individuals heterozygous for LDH-B
      deficiency. Subsequent sequence determination of the mutant alleles revealed
      three novel mutations: an eight-base duplication in exon 3, a four-base
      duplication in exon 4, and a one-base deletion in exon 7 of the LDH-B gene. These
      three mutations result in frame-shift translation and premature termination. In
      addition, the mutations resulting in the duplication of eight or four nucleotides
      appear to cause a decrease in the levels of LDH-B mRNA.

PMID- 8270260
TI  - The T-->C mutation at position +96 of the untranslated region 3' to the
      terminating codon of the beta-globin gene is a rare polymorphism that does not
      cause a beta-thalassemia as previously ascribed.
AB  - We have observed a T-->C mutation at position +96 of the untranslated region 3'
      to the terminating codon of the beta-globin gene in members of two Czech families
      and one black family. Data from initial studies suggested that this change was
      the cause of a beta-thalassemia, but continued analyses have provided convincing
      evidence that this mutation is a simple polymorphism.

PMID- 8270261
TI  - Localisation of the human blue cone pigment gene to chromosome band 7q31.3-32.
AB  - Blue cone pigment (BCP) is one of three types of cone photoreceptors responsible
      for normal colour vision. In this study, the BCP gene has been localised to
      chromosome 7q31.3-32 by fluorescent in situ hybridisation of cosmid clones
      containing the gene. This is consistent with previous mapping of the BCP gene to
      chromosome 7q31-35.

PMID- 8270262
TI  - Highly polymorphic repeat marker within the beta-amyloid precursor protein gene.
AB  - We have identified a polymorphic compound dinucleotide repeat sequence in intron
      1 of the beta-amyloid precursor protein (APP) gene on chromosome 21. Using
      polymerase chain reaction (PCR) amplification of the locus, designated APPivs1,
      we detected 13 alleles in the CEPH family members (heterozygosity = 0.69). Lod
      score analysis showed complete linkage of the marker to the loci D21S210 and
      D21221.

PMID- 8270263
TI  - Corrections to the human mitochondrial ribosomal RNA sequences.
AB  - Two new errors and one consensus change were identified in the human
      mitochondrial Cambridge consensus sequence. The errors are an A to G substitution
      at nucleotide 750 in the 12S rRNA gene and a single nucleotide deletion at nt
      3107 in the 16S rRNA gene. The consensus change is nt 2706 A-->G in the 16S rRNA
      gene.

PMID- 8270264
TI  - Genetic mapping of two loci, DXS454 and DXS458, with respect to the X-linked
      agammaglobulinemia gene locus.
AB  - The dinucleotide repeat sequences at the DXS454 and DXS458 loci have been mapped
      genetically to Xq22, to the interval between DXS3 and DXS17. We have now mapped
      them with respect to XLA and five other loci, to within the DXS3 to XLA interval.
      The more precise localisation of these polymorphic loci will be useful for the
      fine-mapping of disease loci on the long arm of the X chromosome and enable these
      probes to be used for prenatal diagnosis and carrier status determination in
      families with XLA.

PMID- 8270265
TI  - High and low responsiveness to vaccines in farm animals.
AB  - Low responsiveness in some farm animals is emerging as a problem in the
      application of newly developed vaccines which operate at skin surfaces and mucous
      membranes. Breeding for resistance to specific diseases seems to be associated
      with breeding for specific immune responsiveness in farm animals and very likely
      this involves selection for major histocompatibility complex (MHC) haplotype.
      However, other factors contribute to low responsiveness and these include poor
      nutrition, sire effects, antigenic competition and inadequate effector
      mechanisms. The future of newly developed vaccines will rest on the solution to
      the low responder problem, and once solved, the application of these vaccines
      will be fully utilized for disease control in farm animals.

PMID- 8270266
TI  - Recombinant cytokines as immunological adjuvants.
AB  - This paper describes the bacterial expression and purification of bioactive
      recombinant ovine interleukin-2 (rovIL-2), interleukin-1 alpha (rovIL-1 alpha)
      and tumour necrosis factor alpha. These purified proteins had specific activities
      in appropriate bioassays of 1 x 10(7) 1 x 10(7) and 1 x 10(5) U/mg, respectively.
      Recombinant ovIL-1 alpha was assessed as an immunological adjuvant for the sheep
      response to the model protein avidin. When delivered either intradermally or
      intramuscularly in conjunction with avidin in aluminium hydroxide the rovIL-1
      alpha significantly enhanced the secondary humoral response. Doses of 1, 10 or
      100 micrograms per sheep enhanced the humoral response to a similar extent.
      Recombinant ovIL-1 beta had similar adjuvant activity in that it was demonstrated
      to significantly enhance the sheep humoral response to an experimental H.
      contortus antigen. This increase in specific antibody, however, did not correlate
      with enhanced protection against infection with third stage H. contortus larvae.
      In addition incorporation of rovIL-1 beta into the formulation was shown not to
      alter the isotype profile of H. contortus antigen specific antibody.

PMID- 8270267
TI  - Genetically engineered multi-component virus-like particles as veterinary
      vaccines.
AB  - Multiprotein structures can be constructed to mimic virus particles. These
      engineered particles lack genetic material and are not infectious but they can
      elicit protective immune responses in animals against challenges with infectious
      viruses. As a prototype, insect cells were co-infected with two recombinant
      baculoviruses. One recombinant baculovirus contained an insert of L2 and M5
      genes, which encode for outer capsid proteins VP2 and VP5, respectively, from
      bluetongue virus (BTV) downstream of duplicated copies of the baculovirus
      (Autographa californica nuclear polyhedrosis virus, AcNPV) polyhedrin promoter.
      Another recombinant baculovirus expressed two major core proteins (VP3 and VP7)
      from BTV virions. The co-infected cells synthesized non-infectious, double
      shelled, virus-like particles (VLP). The VLP resembled the authentic BTV in size,
      appearance, and biochemical constitution but they lacked the double-stranded-RNA
      genome and three minor polypeptides normally contained in the icosahedral inner
      capsid. The VLP consisted of an outer shell of VP2 and VP5 from US BTV-10
      attached to an icosahedral framework formed by the two major core proteins VP3
      and BTV-17 and VP7 from US BTV-10. Sheep immunized with VLP expressing BTV capsid
      proteins produced antibodies that neutralized homologous serotypes of BTV. The
      assembly of VLP from different proteins simultaneously expressed indicates the
      potential of this novel approach for producing safe and effective vaccines
      against several viral agents.

PMID- 8270268
TI  - Recombinant fowlpox virus vaccines for poultry.
AB  - The intensive poultry industries rely heavily upon the use of vaccines for
      disease control. Viral vector based vaccines offer new avenues for the
      development of vaccines for effective disease control in poultry. Techniques
      developed for the construction of recombinant vaccinia viruses have been readily
      adapted to the construction of recombinant viruses based on fowlpox virus (rFPV).
      The ability to insert several genes into the large genome of fowlpox may enable
      the development of multivalent vaccines and vaccines incorporating immune
      response modifiers such as lymphokines. Newcastle disease, avian influenza,
      infectious bursal disease and Marek's disease antigens expressed by rFPV have
      been shown to be effective vaccines in poultry. None appear, however, to provide
      a substantial improvement in vaccine efficacy. Recombinant FPV will be a valuable
      adjunct to conventional vaccines currently in widespread use. Whether rFPV or
      other vector based vaccines can circumvent the problems of vaccination in the
      presence of high maternally derived antibodies is yet to be resolved. The
      observation that avipoxvirus recombinants may be suitable for the vaccination of
      non-avian species provides an added dimension to vaccines based on FPV or other
      avipoxviruses. Recombinant FPV will find a useful role in poultry disease control
      when used in conjunction with conventional vaccines.

PMID- 8270269
TI  - Recombinant viral vaccines for enzootic bovine leucosis.
AB  - Recently published studies on the development and use of recombinant vaccinia
      virus (VV) vaccines incorporating either the complete envelope (env) gene or only
      a fragment of the env gene consisting of the coding sequence for the env
      glycoprotein 51 (gp51) and part of gp30 of the bovine leukaemia virus (BLV) are
      described. It has been reported that vaccination of sheep with recombinant VV
      vaccines containing the complete env gene appears to protect sheep against
      challenge infection with BLV. The evidence for this protection is based on the
      lack of persistence of high titres of anti-gp51 antibodies compared with
      unvaccinated BLV infected controls, on the enhanced CD4 proliferative responses
      to specific BLV gp51 synthetic peptides in the vaccinated sheep, and on the
      inability to detect BLV pro-virus by polymerase chain reaction in the vaccinated
      sheep after 4 months following challenge infection compared with continual
      detection in unvaccinated sheep over a 16 month trial period. It has been
      suggested that cell-mediated immune responses may be an important aspect of
      protective immunity against BLV infection and it has been reported that large
      tracts of amino acid sequences within the env and pol genes are highly conserved
      in different isolates from different countries which is of importance in
      designing peptide derived vaccines.

PMID- 8270270
TI  - Bovine herpesvirus-1 vaccines.
AB  - Vaccination has been important in controlling a wide variety of viral and
      bacterial infections of man and animals. Vaccines to herpesvirus infection of
      cattle are no exception. The present review describes the different types of
      conventional vaccines that have been used to date and furthermore describes the
      novel approaches which are presently being implemented to develop more effective
      vaccines. These include subunit vaccines as well as genetically engineered
      modified live deletion mutants. Both these novel vaccine approaches appear to be
      more efficacious than conventional vaccines. Furthermore, these vaccines provide
      an additional dimension for control and eradication of infection by providing an
      opportunity to develop companion diagnostic tests to differentiate infected
      animals from vaccinated animals. This review summarizes these developments as
      well as present knowledge regarding the important host defence mechanisms
      required for preventing infection and aiding recovery from infection.

PMID- 8270271
TI  - Circumvention of maternal antibody interference by immunization of newborn pigs
      with glycoprotein gIII-deleted marker vaccine.
AB  - Maternal antibodies interfere with the immunization of swine by modified live
      virus pseudorabies virus (PRV) vaccines. To test the hypothesis that a PRV
      vaccine attenuated by deletions in the thymidine kinase (TK) and gIII genes might
      reduce interference by maternal antibodies, pigs with moderate to low levels of
      colostral PRV antibodies were immunized with the TK- gIII-OMNIMARK-PRV vaccine.
      Vaccinates and non-vaccinates were challenged intranasally with virulent PRV at 7
      weeks of age. In support of the hypothesis, it was found that central nervous
      system (CNS) and/or respiratory disease developed in six out of 10 controls with
      a fatal outcome in one, while two out of 13 vaccinates showed only very mild and
      transient CNS or respiratory disease signs with no fatalities. All vaccinates
      gained weight while non-vaccinates initally lost weight. At post-challenge day
      (PCD) 11, vaccinates showed 4.5 lb/pig greater weight gain than non-vaccinates.
      Virus neutralization (VN) analyses before and after challenge showed that
      vaccinates had been primed immunologically. In another experiment, newborn pigs
      from a pseudorabies disease-quarantined herd with high VN antibody titres were
      vaccinated, respectively, with the gIII-TK-OMNIMARK-PRV vaccine, a TK-gI-gX
      vaccine, or no vaccine and challenged with virulent PRV at 14 weeks of age when
      VN titres were < 1:2. By PCD 9, the TK-gIII-group had outgained the TK-gI-gX- and
      the control groups, respectively, by 6.0 and 3.2 lb per pig.

PMID- 8270272
TI  - Vaccination against tuberculosis: is BCG more sinned against than sinner?
AB  - While extensive experimental studies of tuberculosis (Tb) have provided the
      foundation data for the discovery of cell-mediated immunity, there remains much
      to be disclosed about the critical pathways of immunity involved in this
      infectious process and the factors necessary to produce protective immunity.
      Studies on the aetiology and pathology of this disease have failed to elucidate
      the mechanisms of protective immunity. Although Tb research has been neglected
      for the past 30 years, the re-emergence of Tb worldwide as a significant zoonotic
      disease has re-focused research in this area. Scientific solutions for the
      control of Tb in man or domestic animals have not been found using empirical
      methods. Composite studies involving animal models of experimental infection will
      be necessary to critically evaluate vaccine efficacy and eludiate the basic
      immunological mechanisms involved in both disease and immunity. Available data
      which suggest that disease-related hypersensitivity and immunity are dissociable
      highlight the prospect that immunity to infection may be induced without
      compromising the continued need for ongoing systems of immunodiagnosis to exclude
      disease. In populations with a high prevalence of disease it is likely that a
      combination of immunodiagnosis, chemotherapy and immunoprophylaxis will be
      required to eradicate the disease.

PMID- 8270273
TI  - Vaccination against cestode parasites.
AB  - Cestodes are tapeworm parasites. Infection in the intermediate host with larval
      (metacestode) parasites causes medically and economically important diseases
      known as hydatidosis and cysticercosis. Immunization against experimental
      infection with metacestode parasites has been highly successful, in marked
      contrast with the relative ineffectiveness of vaccines against infection with
      most parasitic organisms. High levels of immunity against a challenge infection
      with taeniid cestode eggs can be stimulated by immunization with extracts of the
      parasites, particularly with extracts of the oncosphere life-cycle stage. This
      led to the production of a recombinant antigen vaccine against infection in sheep
      with the parasite Taenia ovis, the first highly effective, non-living vaccine
      against a parasitic infection in animals or humans. This paper reviews immunity
      to the adult and metacestode life-cycle stages of cestode parasites, development
      and application of the T. ovis vaccine, and prospects for vaccines against other
      cestode infections.

PMID- 8270274
TI  - Vaccination against Lucilia cuprina: the causative agent of sheep blowfly strike.
AB  - The sheep blowfly, Lucilia cuprina, is responsible for over 80% of cases of
      blowfly strike in Australia and the losses in production and sheep deaths due to
      flystrike exceed $200 million per annum. Traditional methods of control are
      becoming less effective because of the blowfly's resistance to insecticides and
      thus other methods of control are necessary. In general, sheep develop very
      little immunity to flystrike even after repeated infestation, however vaccination
      against L. cuprina has shown considerable potential for controlling flystrike.
      The most successful sources of antigens have been the larvae's secreted proteases
      and several extracts from gut or peritrophic membrane. Immunization with these
      antigens results in retardation of larval growth and in some cases larval
      mortality. On sheep immunized with peritrophic membrane extracts, the growth
      retardation appears to be caused by a blocking of the peritrophic membrane which
      results in the larvae being starved of nutrients. The prospects for vaccine
      development and the remaining barriers to be overcome are discussed.

PMID- 8270275
TI  - Production of vaccines against gastrointestinal nematodes of livestock.
AB  - Three international collaborations involving Australian research scientists are
      currently developing vaccines against Haemonchus, Trichostrongylus and Ostertagia
      parasites using recombinant DNA technology. The variety of protective antigens
      identified can be classified as 'conventional' (stimulate naturally acquired
      immunity) or 'novel'/'convert'/'concealed' (protective once immunity is induced
      by vaccination). To date, the most gratifying progress has resulted in 60-90%
      protection against Haemonchus and other blood-sucking parasites (e.g. ticks)
      using novel antigens, where high titres of serum antibody ingested by feeding
      worms leads to their demise. A great deal of research effort is unravelling the
      complexity of naturally acquired immunity so that conventional antigens, which
      may be the principal means of removing 'mucosal-browsing' parasites, may be
      formulated and delivered to achieve optimal efficacy. This work reveals that to
      remove early stages of parasites before they take up residence, deliberate
      induction of hypersensitivity responses akin to asthma, may be a desirable goal
      for vaccines and that the two models have much in common.

PMID- 8270276
TI  - Immunological approaches to fertility regulation in domestic livestock.
AB  - Antibodies to hormones have been used extensively to study endocrine regulation
      of reproduction and in recent times they have been commercially exploited as
      therapeutic agents to manipulate reproduction. Despite the release of two
      commercial products, little is known about the mechanism of action of
      immunoneutralization. The presence of hormone-binding antibodies in the
      circulation and the detection of hormone antibody complexes in blood has led
      investigators to suggest a vascular site of action for immunoneutralization.
      However, a vascular site of action is difficult to reconcile with some of the
      known effects of immunoneutralization to the boar taint steroid (5 alpha-androst
      16-en-3-one) to androstenedione and to gonadotrophin-releasing hormone. In this
      paper we review some of our recent research into the mechanism of action of
      androstenedione immunoneutralization. We suggest that hormonal
      immunoneutralization of androstenedione may take place in the extracellular
      compartment or within the plasma membrane where antibodies to androstenedione may
      bind to a specific steroid-binding protein in the plasma membrane of granulosa
      cells.

PMID- 8270277
TI  - Immunocastration of colts and immunospeying of fillies.
AB  - A series of experiments using an ovalbumin conjugated gonadotrophin releasing
      hormone was used to stimulate antibody production, suppress testosterone
      secretion and depress testicular function in yearling and 2 year old colts and
      fillies. In the preliminary experiment, an injectable oil-based formulation was
      administered to yearling colts. Testicular development and testosterone secretion
      were retarded for a period of approximately 28-32 weeks while antibody titres
      were greater than 1:1000. An implant and water-soluble vaccine (200 and 400 mg)
      is presently being tested in 2 year old colts. Testicular dimensions and
      testosterone concentrations decreased following vaccination. Preliminary results
      indicate that the effects of the implant are reversible and last for
      approximately 30 weeks. The water-soluble vaccine produced effective antibodies
      for 10-19 weeks. Plasma testosterone of all colts was reduced to gelding levels
      (0.2 ng/mL) while antibody titres were greater than 1:1000. Semen evaluation,
      morphometric analysis and daily sperm production data indicate that the testes
      recovered normal function. These experiments are continuing and more definitive
      data on the vaccine and its reversibility will be available at their conclusion.
      Ovarian activity of the treated fillies (200 and 400 mg) ceased soon after
      vaccination. Their progesterone concentrations have remained below 1 ng/mL for 20
      weeks. The untreated control fillies have continued to cycle normally as
      determined by ovarian ultrasonography and progesterone concentrations.

PMID- 8270278
TI  - Inversion of carcinogen-promoter sequence: effects on mouse skin tumorigenesis
      and cellular growth kinetics.
AB  - To stimulate conditions wherein humans might be exposed to tumor promoters prior
      to carcinogenic stimulus, female S/RV Cri mice were treated with 12-O
      tetradecanoylphorbol-13-acetate (TPA) for 10 weeks followed by a sc injection of
      3-methylcholanthrene (MCA). Six weeks after MCA administration, tissue
      alterations in different skin layers were analysed by histology, morphometry and
      autoradiography. Multiple application of TPA prior to MCA injection induced
      moderate to marked epidermal hyperplasia with an increase in the thickness of
      nucleated cell layers and stratum granulosum. As compared to control, number of
      basal and suprabasal cells per 7.5 mm of interfollicular epidermal (IFE) length
      was significantly higher in the skin of animals treated with TPA + MCA. The
      hyperplastic response was accompanied by a significant increase in epidermal
      mitotic activity, number of cells in DNA-synthetic phase in epidermis, dermis and
      subcutis and subepidermal mast cell population. Histological observations of
      induced tumors revealed a significant increase in the incidence of carcinomas and
      mixed neoplasms of epithelial and mesenchymal histogenesis. The findings suggest
      that stimulated cellular proliferation in different layers of mouse skin by TPA
      treatment prior to MCA injection may play a major role in enhanced expression of
      histogenetically distinct tumors.

PMID- 8270279
TI  - Isolation and characterization of nonhistone proteins associated with DNase-II
      hypersensitive sites of Sarcoma-180 chromatin.
AB  - Limited digestion (2 min) of Sarcoma-180 nuclei by DNase-II released two
      nonhistone proteins from the hypersensitive sites of chromatin. The apparent
      molecular weights of these two proteins were 34 and 21 kDa. These proteins showed
      a moderate but specific inhibition in in vitro cell free transcription assay with
      native chromatin as template as opposed to no effect on native DNA transcription.

PMID- 8270280
TI  - Short term treatment of tamoxifen and estradiol on estradiol and progesterone
      receptors in rabbit uterus.
AB  - Effects of tamoxifen (Tam) on cytosolic estradiol (E2) receptors (ERc),
      progesterone (P4) receptors (PRc), nuclear estradiol (ERn) and progesterone
      receptors (PRn) were studied in adult normal rabbit uterine tissue. The ratio of
      cytosol: nuclear estradiol receptors (ER) was greater in rabbits treated with Tam
      than E2 or control uterine tissues. Rabbit uterine progesterone receptors (PR) in
      E2 treated animal were greater than Tam-treated animals. Tam caused nuclear
      accumulation of estradiol receptor, and simultaneous administration of E2 + Tam
      500, estradiol could not revert Tam mediated accumulation of ER. The results
      suggest that Tam has an essentially antagonist action in the rabbit uterine
      tissue.

PMID- 8270281
TI  - Effect of synthetic nonapeptide (Thr-Cys-Ser-Val-Ser-Glu-Trp-Gly-Ile) on ovarian
      follicular development in the bull frog Rana tigrina (Daud).
AB  - Effect of synthetic nonapeptide (Thr-Cys-Ser-Val-Ser-Glu-Trp-Gly-Ile)
      representing the amino acid sequence 86-94 of human seminal plasma was studied on
      the ovarian follicular growth in the bullfrog R. tigrina during preparatory phase
      of reproductive cycle. Daily (except on Sundays) injections of 10 micrograms
      nonapeptide for one month caused a significant increase in ovarian weight and
      number of second growth phase (SGP) or vitellogenic oocytes. The results suggest
      that the nonapeptide is biologically active in amphibians also.

PMID- 8270282
TI  - Patterns of heavy metal resistance in marine Pseudomonas MR1.
AB  - Pseudomonas strain MR1 isolated from the coastal waters of Bay of Bengal was
      found to resist Hg, As, Cd, Cu, Zn and Pb. It efficiently detoxified both organic
      and inorganic mercuric compounds to non toxic metallic mercury by an inducible
      enzyme, mercuric reductase. Its resistance to arsenic might be due to energy
      dependent arsenate efflux system. Cadmium was detected intracellularly and in the
      surrounding medium. The bacterium accumulated copper and lead intracellularly.

PMID- 8270283
TI  - Effect of calcium channel blockers and salbutamol on oxytocin and PGF2 alpha
      induced uterine contractions in rats.
AB  - Calcium channel blockers verapamil (2, 10nM), diltiazem (11, 22nM), nifedipine
      (2.9, 14nM) and salbutamol (21, 42nM) produced concentration dependent inhibition
      of oxytocin induced contractions in non-pregnant rats. With verapamil and
      nifedipine the effect was more marked at both low and high doses. Verapamil
      (1,2nM), diltiazem (2.2, 11nM), nifedipine (1.4, 2.9nM) and salbutamol (2.1,
      4.2nM) produced significant inhibitory effect on PGF2 alpha (0.3 microgram)
      induced phasic tension. However, basal tension was significantly reduced by
      salbutamol and nifedipine only.

PMID- 8270284
TI  - In vitro transdermal delivery of atenolol using mouse and guinea pig.
AB  - In vitro percutaneous absorption of atenolol was done in order to assess its
      feasibility for transdermal development across mouse and guinea pig skins using
      Keshary-Chien type of diffusion cell. Values of diffusion rate (J) and
      permeability coefficient (Kp) across guinea pig skin were lowered as compared to
      those in mouse skin. When the concentration of drug in donor compartment was
      increased a decrease in Kp and increase in J value were observed with both the
      skins. Under the same conditions, values of J and Kp were lowered for dorsal skin
      compared to abdominal skin both for mouse and guinea pig. The results suggest
      that atenolol can be pursued further for transdermal system development.

PMID- 8270285
TI  - Effect of vitamin-E on high fat diet induced hyperlipidemia in rats.
AB  - High fat diet intake in rats resulted in hyperlipidemia which was evidenced by
      elevated levels of plasma cholesterol, free fatty acids, triglycerides and
      increased LDLc/HDLc ratio. Vitamin E (400 mg/kg body wt/day) administration for
      60 days prevented the elevations in plasma lipid levels. It reduced LDLc/HDLc
      ratio, lipid peroxide levels and elevated the level of reduced glutathione (GSH)
      in hyperlipidemic rats. Vitamin-E was non-toxic.

PMID- 8270286
TI  - Effect of anti-oxidants and adsorbents on tissue browning associated metabolism
      in Cocculus pendulus callus cultures.
AB  - Explants and callus of C. pendulus produced intense brown substances in the
      medium which caused necrosis. Various anti-oxidants (ascorbic acid, cysteine and
      dithiothreitol) and adsorbents (activated charcoal and polyvinyl pyrrolidone)
      were used in different concentrations to prevent browning of the tissues. These
      in MS medium affected differently the growth, colour and texture of the tissues.
      It was concluded that both peroxidase and phenolase were involved in the
      browning. Increased peroxidase activity and decreased phenolase activity were
      probably due to more peroxidative oxidation of phenols and unavailability of
      substrate for phenolase activity. This resulted in faster growth of tissues,
      which further reduced the phenolase activity.

PMID- 8270287
TI  - Persistent diarrhea and malabsorption in children.

PMID- 8270288
TI  - Treatment of variceal bleeding in the '90s.

PMID- 8270289
TI  - Spectrum of malabsorption syndrome in north Indian children.
AB  - AIMS: To know the spectrum of malabsorption syndrome (MAS) in infants and
      children and highlight agewise differences in etiology in different age groups.
      METHODS: 137 children presenting with diarrhea of more than 3 weeks' duration
      and/or growth failure and abnormality of one of more tests of malabsorption were
      studied. Etiology of MAS was determined using investigations specific for each of
      the causes. RESULTS: Sixty two (45%) children were below 2 years of age and 75
      (55%) above. Common causes of MAS were: protracted diarrhea 45 (33%), celiac
      disease 35 (26%), parasitic infestations 13 (9%), milk protein intolerance 8
      (6%), intestinal tuberculosis 7 (5%). In 18 (13%) patients, cause of MAS could
      not be determined. Protracted diarrhea (73%) and milk protein intolerance (13%)
      constituted the major etiology of MAS in children below 2 years of age, whereas
      celiac disease (43%), parasitic infestations (15%) and intestinal tuberculosis
      (9%) were the common causes in children above 2 years of age. CONCLUSION: The
      spectrum of MAS in Indian children in different age groups is distinctly
      different from that seen in developed countries.

PMID- 8270290
TI  - A double-blind clinical trial of kamalahar, an indigenous compound preparation,
      in acute viral hepatitis.
AB  - BACKGROUND: Kamalahar is an indigenous preparation reported to be beneficial in
      acute viral hepatitis. AIMS: To evaluate the efficacy of Kamalahain acute viral
      hepatitis in a double-blind, placebo-controlled study. METHODS: Fifty two
      patients with acute viral hepatitis were randomized to receive either Kamalahar
      500 mg or a matched placebo three times a day for 15 days. Forty four patients
      (Kamalahar 20; placebo 24) completed the trial. RESULTS: Improvement in clinical
      signs was more marked with Kamalahar compared to placebo. The fall in serum
      bilirubin (p < 0.001), SGPT (p < 0.001) and serum alkaline phosphatase (p <
      0.005) at day 15 was significantly greater with the drug. No significant side
      effects were observed. CONCLUSION: Kamalahar offers therapeutic promise in acute
      viral hepatitis.

PMID- 8270291
TI  - Spectrum of lower gastrointestinal hemorrhage: an endoscopic study of 166
      patients.
AB  - BACKGROUND: The spectrum of lesions causing lower gastrointestinal hemorrhage
      shows marked geographic variation. The study was aimed to determine this spectrum
      in our region using endoscopic examination. METHODS: 166 patients presenting with
      lower gastrointestinal hemorrhage were investigated using colonoscopy as the
      first investigation. RESULTS: Lesions responsible for bleeding could be
      identified in 141 patients (84.9%). In 25 patients (15.1%), the etiology of bleed
      could not be determined either because of failure to identify a lesion (10
      patients) or because of an incomplete examination (15 patients). Major causes of
      lower gastrointestinal bleeding included idiopathic ulcerative colitis (19.3%),
      acute colitis (12.0%), colonic polyps (10.2%), radiation colitis (9.0%), solitary
      rectal ulcer (7.8%), colonic carcinoma (7.2%), colonic tuberculosis (4.2%) and
      enteric fever (3.0%). CONCLUSION: Endoscopic examination is very useful in
      evaluating patients with lower gastrointestinal hemorrhage. The predominant
      causes of lower gastrointestinal bleeding in our experience are different from
      those reported from western countries.

PMID- 8270292
TI  - Alternate-day therapy with omeprazole for duodenal ulcer.
AB  - BACKGROUND: Maximal acid suppression produced by a single dose of 20 mg
      omeprazole has been reported to persist for over 24 hours, with acid secretion
      returning to normal after 2 days. OBJECTIVES: (i) To study the effect of single
      oral dose of 20 mg omeprazole on maximal acid output (MAO) and peak acid output
      (PAO) in duodenal ulcer patients and healthy volunteers. (ii) To compare the
      efficacy of omeprazole 20 mg daily versus 20 mg on alternate days in the
      treatment of duodenal ulcer. STUDY DESIGN: Open randomized comparative trial.
      METHODS: MAO and PAO were estimated in five duodenal ulcer patients and five
      healthy volunteers before, and 24 hours and 48 hours after, a single 20 mg oral
      dose of omeprazole. Fifty eight consecutive uncomplicated duodenal ulcer patients
      were randomized to receive omeprazole 20 mg either daily (n = 30) or on alternate
      days (n = 28) for four weeks. The two groups were matched for age, sex, duration
      of ulcer symptoms, smoking, NSAID use, and ulcer size at entry. Symptom scores
      using a pre-defined scoring system and endoscopic ulcer healing rates were
      evaluated at 2 and 4 weeks. RESULTS: MAO and PAO showed significant reduction in
      both duodenal ulcer patients and healthy controls 24 hours after 20 mg
      omeprazole. Reduction at 48 hours was significant in duodenal ulcer patients but
      not in controls. Endoscopic healing rates of duodenal ulcer at 2 and 4 weeks were
      80% and 93.3% respectively in the daily treatment group and 71.4% and 85.7%
      respectively in the alternate-day treatment group. These differences were not
      statistically significant. CONCLUSION: 20 mg omeprazole on alternate days is as
      effective as 20 mg daily (i) in suppressing MAO and PAO and (ii) in the treatment
      of duodenal ulcer.

PMID- 8270293
TI  - Corrosive injury to the upper gastrointestinal tract.
AB  - Corrosive injury to the UGI tract is a common problem and has a wide spectrum of
      presentations. Unlike in the West, where lye ingestion is more frequent,
      corrosive injury in India is more commonly due to acids. Depth of the injury is
      the most important factor which determines the outcome. Endoscopy done soon after
      corrosive ingestion is safe and is very helpful in assessing the extent and
      severity of injury and in planning proper management of these patients. At
      present no therapy has been proven to be effective for prevention of stricture
      formation. Endoscopic dilatation seems to be the treatment of choice for
      management of most esophageal strictures with very good short and long term
      results. Surgery should be considered only when dilatation fails.

PMID- 8270294
TI  - Communication at scientific meetings: in support of posters.

PMID- 8270295
TI  - Nephrotic syndrome in non-cirrhotic portal fibrosis: a report of three cases.
AB  - We describe three patients with nephrotic syndrome and non-cirrhotic portal
      fibrosis. In two of them, the liver disorder preceded the nephrotic syndrome
      while in the third patient the two conditions presented together. All three
      patients achieved remission of nephrotic syndrome with prednisolone and
      cyclophosphamide.

PMID- 8270296
TI  - Primary hepatic lymphoma mimicking fulminant hepatic failure.
AB  - A patient with clinical presentation mimicking fulminant hepatic failure was
      found to have primary non-Hodgkin's lymphoma of liver on autopsy. He had tender
      nodular hepatomegaly, elevated liver enzymes and appearance of a diffuse
      infiltrative disorder on sonography. Extensive diffuse infiltration may be the
      dominant factor for the rapid hepatocellular failure in this case.

PMID- 8270297
TI  - Intrapulmonary vascular dilatations with hypoxemia in extrahepatic portal vein
      obstruction.
AB  - Several mechanisms have been suggested for the development of hypoxemia in
      cirrhosis. A few patients of portal hypertension due to non cirrhotic liver
      disease with cyanosis have also been reported earlier. We report probably the
      first documented case of portal hypertension with portal cavernoma and a normal
      liver, who had intrapulmonary vascular dilatations leading to hypoxemia and
      cyanosis. Our case suggests that changes leading to hypoxemia can occur due to
      portal hypertension alone, in the presence of a normal liver.

PMID- 8270298
TI  - Primary Hodgkin's disease of small intestine: a report of two cases.
AB  - Two patients with primary Hodgkin's disease of the small intestine are reported
      because of rarity of this condition. Both patients presented with primary
      intestinal symptoms and were diagnosed after surgical resection. The modalities
      of treatment and favorable long term survival are presented.

PMID- 8270299
TI  - Prestomal ileitis.
AB  - A case of prestomal ileitis resulting from incomplete ileostomy-stomal
      obstruction presented with intestinal perforation and massive bleeding
      perileostomy. The diagnosis and surgical implications of this unusual problem
      have been discussed.

PMID- 8270300
TI  - Endomysial antibody and celiac disease.

PMID- 8270301
TI  - Hepatitis C virus and autoimmune chronic active hepatitis.

PMID- 8270302
TI  - Circanual variation of sperm count and motility in men.
AB  - Seasonal variation in rhythmicity of spermatogenesis might be due to external
      temperature fluctuation which could partially be responsible for decreased sperm
      counts in summer. Other factor like exposure to light might contribute for the
      reduction in sperm counts. These facts should be taken into account before
      diagnosing male fertility.

PMID- 8270303
TI  - Anaerobic infection in chronic maxillary sinusitis.
AB  - 1) Ten per cent of cases of chronic maxillary sinusitis in a series of 50 cases
      treated in the ENT department of Dayanand Medical College, Ludhiana, were caused
      by anaerobic infection. 2) The causative anaerobic micro-organisms encountered
      were Peptostreptococcus and Clostridium species. 3) Treatment should, therefore,
      include metronidazole, especially in those cases refractory to conventional
      antibiotic therapy.

PMID- 8270304
TI  - LDH-x in azoospermia: a new diagnostic alternative to vasography and testicular
      biopsy.
AB  - Activities of different isozymes of lactate dehydrogenase were studied in semen
      samples from fertile, and different groups of infertile men. No isozyme except
      the sperm specific LDH-x or C4 showed any difference in activity with changes in
      sperm density. Activity of LDH-x exhibited a trend positive to changes in sperm
      density and became absent in obstructive and vasectomized azoospermia. Among
      other types of azoospermia, the activity became very high in maturation arrest
      but very low in patients with testicular biopsy showing germ cell aplasia, such
      as in SCOS and ghostlike tubules. Diagnostic usefulness of the estimation of LDH
      x activity in semen is discussed.

PMID- 8270305
TI  - The patient as a team member--on the receiving end.

PMID- 8270306
TI  - Maxillary implants and the growing patient.
AB  - Maxillary skeletal and dental growth results in dramatic changes in all three
      dimensions during active growth. Experimental evidence and the behavior of
      ankylosed teeth suggest that an osseointegrated object remains stationary in the
      bone surrounding it and does not move or adapt to bone remodeling. Growth changes
      may result in the burying or loss of implants depending on the placement site.
      Hence, implants placed in the early mixed dentition have a poor prognosis of
      continued usefulness through puberty. When placed early, implants may disturb
      growth or have to be replaced. Implants placed during late puberty or early
      adulthood have the best change for long-term usefulness.

PMID- 8270307
TI  - Immediate implant surgery: three-year retrospective evaluation of 50 consecutive
      cases.
AB  - Since August 1989, 35 consecutive patients were treated with immediate implants
      to replace 50 teeth requiring extractions as a result of root fractures,
      endodontic instability, nonrestorable carious lesions, or periodontal disease.
      Defects relative to the implant were morphologically grouped and were treated for
      bone regeneration with demineralized freeze-dried crushed cancellous bone
      (DFDBA), e-PTFE membrane, or both. Thread exposure initially ranged from 4 to 20
      threads, while implant lengths varied from 8.5 to 18 mm. The mean implant length
      was 15 mm, with mean thread exposure of 11.34 threads, or 54% of the threaded
      length of the implant. Reentry confirmed 100% thread coverage in all but one
      implant in the no-wall group treated with DFDBA alone. Histologic evaluation of
      three cases confirmed viability of the regenerated bone. The patients were
      followed through April 1993, with 49 implants (98%) remaining osseointegrated and
      functional, supporting the predictability of immediate implant placement. The age
      of the patients ranged from 16 to 80 years, hence implant placement
      considerations relative to adolescents are also discussed.

PMID- 8270308
TI  - The wide fixture: a solution for special bone situations and a rescue for the
      compromised implant. Part 1.
AB  - This paper describes a new 5.0-mm-diameter self-tapping implant, a modification
      of the standard Branemark fixture designed to increase the amount of bone-to
      titanium surface contact and to capture dense bone at the lateral and crestal
      borders of the alveolus. Indications for its use include (1) areas of inadequate
      bone height, (2) areas of poor bone quality (type IV), and (3) immediate
      replacement of non-integrated or fractured implants. This preliminary report
      discusses the design alterations and surgical techniques available to treat these
      difficult bone situations.

PMID- 8270309
TI  - Fractures of the fixture component of an osseointegrated implant.
AB  - The cause of mechanical failure of the fixture component of an osseointegrated
      dental implant was investigated. The surfaces of five clinical specimens that had
      fractured were compared to those of new specimens fractured in the laboratory
      under monotonic and cyclic loads. Scanning electron microscopy revealed
      striations on the fractured surfaces of the clinical specimens, similar to
      striations on the laboratory-fatigued specimens and in contrast to the dimpled
      surfaces on the overloaded specimens. The investigation demonstrated that
      fractures of the fixture component of this dental implant occurred by fatigue
      under physiologic loads, with marginal alveolar bone loss around the fixture.

PMID- 8270310
TI  - The effects of hyperbaric oxygenation on bone-titanium implant interface strength
      with and without preceding irradiation.
AB  - This study investigated the influence of a single 15-Gy dose of irradiation on
      the capacity of titanium screws to integrate in irradiated bone tissue. The
      biomechanical force necessary to unscrew the titanium implants 8 weeks after
      placement was 54% lower for implants in irradiated bone tissue compared to
      implants in nonirradiated bone tissue. Postirradiation use of hyperbaric oxygen
      treatment at 2.8 ATA (2-hour daily treatments for 21 days) increased the
      biomechanical force necessary to unscrew the titanium implants by 44% in
      irradiated bone and by 22% in nonirradiated bone.

PMID- 8270311
TI  - Measurement of the interface between bone and immediate endosseous implants: a
      pilot study in dogs.
AB  - This study developed methodology to evaluate the healing of 15 IMZ implants
      placed in the sockets of freshly extracted mandibular premolars in three adult
      mongrel dogs. Six surgical sites were prepared in each animal and one site was
      left as a control. Porous hydroxyapatite was placed around the top half of two
      implants in each animal; one implant was also covered with
      polytetrafluoroethylene membrane. All implants were covered with a mucoperiosteal
      flap and sutured closed. Upon animal sacrifice, the mandibles were retrieved for
      block dissection and the blocks were embedded in plastic. Serial longitudinal
      wafers were ground to 50 to 100 microns and stained. Standard photomicrographs
      were taken so that tracings of the implant-bone interface could be measured on a
      sonic digitizer. The mean percent amount of bone to plasma-sprayed portion of the
      implant on the longitudinal sections was 47.9% +/- 5.2% with a range of 17.4% to
      84.7%. The horizontal sections were measured at 53.5% +/- 3.7% with a range of
      0.0% to 100%. This pilot study suggests that IMZ implants placed in fresh
      extraction sockets can achieve a degree of intimate contact with bone; however,
      wide variation in the implant-to-bone interface was found even in the same
      specimen.

PMID- 8270312
TI  - The successful application of osseointegrated implants to the posterior jaw: a
      long-term retrospective study.
AB  - This long-term study has demonstrated the successful use of osseointegrated
      implants to replace posterior teeth in the partially dentate patient. A total of
      1,203 Nobelpharma implants placed by two periodontists practicing in traditional
      office settings were included in the survey. Of the 551 implants placed in the
      mandible, 25 failed, for a success rate of 95.5%. Of the 247 mandibular
      prostheses fabricated for 200 mandibles, 8 failed, for a prosthesis stability
      rate exceeding 97%. Of the 652 implants placed in the maxilla, 31 failed, for a
      success rate of 95.2%. Of the 250 maxillary prostheses fabricated for 193
      maxillae, 2 failed, for a success rate exceeding 99%. The results compare
      favorably to previous reports in terms of implant survival and stability.

PMID- 8270313
TI  - Precise site location for implants using CT scans: a technical note.
AB  - Information gained by preoperative imaging techniques must be accurately related
      to the surgical site. The inability to do this severely diminishes the benefit of
      the diagnostic imaging. The CT scan is capable of providing considerable
      information regarding the jaws. The use of radiopaque markers to identify
      preselected points on the image is readily done by placing markers in the wax
      registration rims that are worn during the scan. The position of these markers is
      transferred to the mouth with a surgical template, facilitating surgery and
      reducing the incidence of anatomic accidents caused by lack of orientation.

PMID- 8270314
TI  - Evaluation of master cast techniques for multiple abutment implant prostheses.
AB  - This study compared the accuracy of three techniques used to fabricate master
      casts for implant prostheses. A metal model with six implants and standard
      abutments and a matching template were fabricated. Impressions of the model were
      made in Impregum and cast in Die Keen. The casts were divided into three groups
      of 15 casts: group A--solid casts; group B--Pindex; and group C--Zeiser system.
      Each cast was visually evaluated for fit of the template. Positional accuracy of
      the abutments was numerically assessed using an optical comparator. Visual
      analysis showed that only casts sectioned with the Zeiser system allowed a
      passive fit of the template. Statistical analysis of numerical findings indicated
      that casts made with the Zeiser system were significantly more accurate than
      solid casts, which in turn were more accurate than those made with the Pindex
      system.

PMID- 8270315
TI  - Guided bone regeneration at a fenestrated dental implant: histologic assessment
      of a case report.
AB  - Guided tissue regeneration has been shown to establish new attachment in
      periodontal defects and to facilitate hard tissue repair around dental implants.
      This case report describes a patient treated with guided tissue regeneration
      adjacent to an endosseous dental implant. Histologic analysis showed the
      regenerated tissue to be mature, cortical bone possessing a high level of
      mineralization.

PMID- 8270316
TI  - A preventive mucosal flap technique for use in implantology.
AB  - A flap technique designed for use in dental implantology is described. This
      technique creates a more homogeneous mucosa around the implants and reduces its
      thickness to prevent the introduction of deep mucosal pockets around the
      implants. The technique results in the preservation of a maximum of fixed mucosa
      and a shallow pocket next to the implant, which aids in optimizing oral hygiene
      and prognosis. The technique can be performed at the time of implant placement.
      The flap covers the implants completely and closes the wound primarily. This
      technique was compared to a conventional flap technique and was clinically found
      to give significantly better results.

PMID- 8270317
TI  - Correction of implant malalignment by segmental osteotomy: a case report.
AB  - This case report demonstrates that the position of malaligned osseointegrated
      implants can be corrected by a segmental osteotomy procedure with no loss of
      implants or bone support. The patient was a healthy teenage girl who sustained
      facial trauma with loss of teeth and alveolar bone. The defect was initially bone
      grafted. Branemark implants were simultaneously placed in the graft. Their
      initial unfavorable positions and inclinations were later corrected by a
      segmental osteotomy.

PMID- 8270318
TI  - International classification of rodent tumours. Part I--The rat. 4.
      Haematopoietic system.

PMID- 8270319
TI  - International classification of rodent tumours. Part I--The rat. 5. Integumentary
      system.

PMID- 8270320
TI  - Depth of anesthesia. Preface. The conscious-unconscious interface.

PMID- 8270321
TI  - Clinical and medicolegal aspects of conscious awareness during anesthesia.
AB  - In summary, regarding the legal aspects of awareness during anesthesia, the
      questions for the court to answer are: Was the patient aware? If probably yes,
      did the anesthesia technique cause or materially contribute to the awareness?
      Alternatively, if res ipsa loquitur applies, can the anesthesiologist show that
      the technique was not negligent, if necessary by showing that it would have been
      acceptable to at least a responsible minority of practitioners? It will be clear
      from the foregoing that good recordkeeping cannot be overemphasized. Apart from
      the fact that a precise and clear record tends to convince the court that they
      are dealing with a careful practitioner, the most important factor is that the
      more you have recorded about the anesthesia course, the more you will be able to
      tell the court about it. Finally, if you are unfortunate enough to lose and the
      patient is awarded damages, how much will the patient get? In the United Kingdom
      recently, $20,000 was awarded to patients for awareness in orthopedic and
      obstetric cases--perhaps a modest amount by U.S. standards. If the patient
      develops posttraumatic stress disorder, a much larger award is likely, especially
      if the patient is unable to work as a result of it; loss of earnings always
      increases an award, and it could easily reach $750,000 for a big earner.
      Insurance or other indemnity should cover this, of course, but it pays to
      remember one's likely exposure to risk in the event of failing to pay one's
      premium.

PMID- 8270322
TI  - Depth of anesthesia. Clinical use of the 40-Hz auditory steady state response.

PMID- 8270323
TI  - Depth of anesthesia. Electroencephalogram and evoked potential analysis: a model
      based approach.

PMID- 8270324
TI  - Depth of anesthesia. Consciousness: current views.

PMID- 8270325
TI  - Depth of anesthesia. Temporal mechanisms of consciousness.

PMID- 8270326
TI  - Depth of anesthesia. Human memory and anesthesia.

PMID- 8270327
TI  - Depth of anesthesia. Learning during anesthesia.

PMID- 8270328
TI  - Evaluating depth of anesthesia: review of methods.

PMID- 8270329
TI  - Depth of anesthesia. Midlatency auditory evoked potentials and cognitive function
      during general anesthesia.

PMID- 8270330
TI  - Hirsutism.

PMID- 8270331
TI  - Superficial and deep candidosis.

PMID- 8270332
TI  - Pruritic papular eruption of HIV-disease.

PMID- 8270333
TI  - Nehushtan: side effects of drugs.

PMID- 8270334
TI  - Gratteurs de papier.

PMID- 8270335
TI  - Fatal chickenpox in a patient with nephrotic syndrome.
AB  - BACKGROUND: We report our experience with two patients with adult onset of
      chickenpox in the setting of longstanding steroid therapy for nephrotic syndrome.
      Ours is a 430-bed tertiary care teaching hospital, The Wellesley Hospital,
      Toronto, Ontario. Both patients presented as self-referrals to the emergency
      department. METHODS: The clinical suspicion of chickenpox was rapidly confirmed
      in both cases by a Tzanck smear preparation, by viral cultures of the vesicle,
      serology, and skin biopsy. In both patients therapy with high dose acyclovir, 10
      mg/kg q8h, intravenously, was instituted based on clinical presentation. RESULTS:
      Delay in clinical recognition and treatment in our first case resulted in death
      due to multiorgan failure (MOF). Improved awareness and rapid treatment of the
      second patient had a favorable outcome with no sequelae. CONCLUSIONS: Chickenpox
      is not only a childhood illness. Although rare in the adult population, it is
      associated even in the nonimmunocompromised host with increased morbidity and
      mortality. Steroid therapy predisposes to early dissemination and a potentially
      fatal outcome. Adults with immunosuppression should receive prompt systemic
      treatment with acyclovir.

PMID- 8270336
TI  - Dermatophytosis of children in Kuwait: a prospective survey.
AB  - BACKGROUND: Tinea capitis in children is widely reported, whereas there have been
      only isolated reports on involvement of sites other than the scalp. The purpose
      of this study was to examine the epidemiological features and treatment responses
      of dermatophytosis of children in Kuwait. METHODS: Epidemiological features and
      the treatment responses of 202 consecutive children with dermatophytosis were
      studied. RESULTS: The 202 children constituted 44% of the total dermatophytic
      infections seen during a period of 1 year. Tinea capitis was the most commonly
      encountered infection (78%), followed by tinea corporis, tinea faciei, tinea
      cruris and manus, respectively. Microsporum canis was the most prevalent species
      (96%) in this region. A history of pets at home could be elicited in 52% of the
      cases. A familial occurrence of similar infections was seen in 56% of the
      patients. In patients with tinea capitis, addition of topical clotrimazole or
      ketoconazole to oral griseofulvin produced better therapeutic results compared to
      griseofulvin alone or in combination with selenium sulfide shampoo. CONCLUSIONS:
      Tinea capitis is the most common dermatophytic infection in children. Thirty
      percent of the children may have dermatophytosis at sites other than the scalp. A
      combination of topical clotrimazole or ketoconazole with oral griseofulvin is
      superior to griseofulvin alone or in combination with selenium sulfide shampoo in
      the treatment of tinea capitis.

PMID- 8270337
TI  - Leishmaniasis recidiva cutis in American cutaneous leishmaniasis.
AB  - BACKGROUND: Leishmaniasis recidiva cutis (LRC) consists of active lesions around
      or inside the scar of classical cutaneous leishmaniasis (CL). In the literature
      it is considered as an hyperergic form of CL because the patients show a strong
      response to intradermal testing with leishmania antigen and, histologically, the
      parasites are scarce or absent; a well-organized granuloma is always observed.
      METHODS: Three patients from Bahia (Brazil) with LRC were evaluated by clinical
      examination, biopsies, skin tests with leishmania antigen, serology, and culture.
      In addition, a specific lymphocyte blastogenesis test was done and the species of
      leishmania characterized. RESULTS: The disease was caused by both L. amazonensis
      and L. braziliensis and serological titers varied from 1/16 to 1/64. The patients
      presented histologic and immunologic aspects different from those referred to in
      the literature. From four biopsies obtained only two presented a granulomatous
      reaction and parasites varied from absent to a parasite index 3. In one patient
      an absence of T cell response to leishmania antigen was observed in the first
      evaluation with restoration of the response after cure. In the other two, the
      degree of the specific proliferative response was lower than that usually
      observed in patients with classical CL. CONCLUSIONS: These findings indicate that
      New World LRC can not be considered a hyperergic form of CL. With respect to its
      clinical aspects and response to treatment, LRC must be considered as an entity
      different from the classical CL.

PMID- 8270338
TI  - Epidermodysplasia verruciformis in Africans.
AB  - BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare cutaneous disorder
      characterised by persistent, refractory infection with human papillomaviruses
      (HPV). Although EV does not seem to have racial or geographic preference, there
      is a scarcity of reports on its occurrence in Africans. METHODS: Twenty Africans
      with EV were studied, and the literature on this condition in Africans was
      reviewed. Virologic studies were performed on 10 patients. RESULTS: Three types
      of lesions were observed: flat warts, pityriasis versicolor-like macules, and
      seborrheic keratosis-like changes. Malignant transformation occurred in only one
      patient. HPV-3 was isolated only from flat warts, HPV-5 and HPV-17 were isolated
      only from PV-like lesions, whereas an HPV-5-related type was found in all three
      types of changes. HPV-5-related type revealed DNA that was related but not
      identical to any of the viruses in the HPV-5 group. This particular type was
      isolated from all five South African patients with EV in whom virologic studies
      were performed. CONCLUSIONS: The benign nature of EV in dark-skinned Africans has
      been confirmed. Four HPV types have been isolated, of which HPV-related type was
      found in all South African patients with EV and in all types of skin changes,
      regardless of their morphology. African patients with EV frequently present
      seborrheic keratosis-like changes.

PMID- 8270339
TI  - Primary cutaneous nocardia infection due to Nocardia asteroides.

PMID- 8270340
TI  - Creeping disease due to larva of spiruroid nematoda.

PMID- 8270341
TI  - Tuberculosis verrucosa cutis associated with lupus vulgaris.

PMID- 8270342
TI  - Subcutaneous cysticercosis of the tongue mimicking a tumor.

PMID- 8270343
TI  - Trichomonal abscess of the median raphe of the penis.

PMID- 8270344
TI  - Unusual manifestation of demodicidosis in a child.

PMID- 8270345
TI  - Trichotillomania: a trichotillosis, a trichotillotic, or a tic trichotillosis.

PMID- 8270346
TI  - Dermatitis artefacta and sexual abuse.

PMID- 8270347
TI  - Cigarette paper atrophy.

PMID- 8270348
TI  - Betamethasone dipropionate polyacrylic film-forming lotion in the treatment of
      hand dermatitis.

PMID- 8270349
TI  - Limited application of mometasone furoate on the face and intertriginous areas:
      analysis of safety and efficacy.

PMID- 8270350
TI  - Successful treatment of a patient with recurrent furunculosis by vitamin C:
      improvement of clinical course and of impaired neutrophil functions.
AB  - BACKGROUND: Neutrophils play a critical role in host defense against a variety of
      microbial pathogens. There is much information to suggest a role for vitamin C in
      the physiology of neutrophils. Thus, the effects of vitamin C treatment were
      studied in a patient with a history of recurrent furunculosis who showed altered
      neutrophil functions. METHODS: Superoxide generation was measured by cytochrome C
      reduction. Phagocytosis of opsonized zymosan by neutrophils and chemotaxis on
      agarose plates were determined. RESULTS: Chemotaxis, phagocytosis, and superoxide
      generation of the patient's neutrophils were significantly lower than those of
      the matched control. Treatment with vitamin C (500 mg/day) for 30 days caused a
      dramatic clinical response and a significant improvement of all three neutrophil
      functions to values similar to those of the controls. CONCLUSIONS: We suggest
      that the patient described here had a temporary defect in neutrophil functions.
      The treatment with vitamin C probably prevented neutrophil oxidation, thus
      contributing to recovery of neutrophil function and arrest of furunculosis.

PMID- 8270351
TI  - Helistat absorbable collagen hemostatic sponges in cutaneous surgery in HIV-1+
      patients. Military Medical Consortium for the Advancement of Military Medicine
      (MMCAR).
AB  - BACKGROUND: While biopsies are often required for adequate diagnosis of skin
      lesions in HIV-1 infected patients, these procedures result in the possible
      exposure of medical personnel to blood and contaminated instruments. To reduce
      exposure of medical personnel to contaminated needles we have used collagen
      sponges instead of sutures to control bleeding from punch biopsy sites in HIV-1
      infected patients. METHODS: A collagen sponge was placed in all punch biopsy
      sites in HIV-1 infected patients. In cases where there was clinical evidence of
      local infection the sponges were removed 5-6 minutes after hemostasis was
      obtained. RESULTS: In over 500 biopsies in which Helistat collagen sponges were
      used, there have been no cases of secondary infection, and there have been no
      delays in healing. CONCLUSIONS: We believe that the use of these sponges provides
      a high degree of safety for the physician, which may assure that the commonly
      atypical clinical lesions seen in HIV-1 disease are biopsied. In addition, these
      sponges provide hemostasis, particularly significant in this patient population,
      and convenience, without a significant risk of secondary infection, and may
      provide some benefit in healing.

PMID- 8270352
TI  - Indian dermatology.

PMID- 8270353
TI  - Halo seborrheic keratosis associated with colon carcinoma.

PMID- 8270354
TI  - General health, health care utilization, and medical comorbidity in dysthymia.
AB  - OBJECTIVE: This article reviews the literature on the general health, health care
      utilization, prevalence, medical comorbidity, and treatment of dysthymia in
      medical settings. METHOD: The literature was searched by using MEDLINE and by
      reviewing the bibliographies of recent publications. Studies were selected that
      included health data on patients with dysthymia or chronic depression according
      to DSM-III, DSM-III-R, ICD-9, or RDC criteria, or patients who were described as
      having persistent depressive symptoms. RESULTS: This review shows that dysthymic
      patients are at increased risk for poor general health and frequently use medical
      services. Compared to the general population, dysthymia is more prevalent in
      primary care and among patients with various medical and neurological conditions,
      sleep disorders, chronic fatigue, hypothyroidism, and somatoform disorders.
      Pharmacotherapy is effective, but has not been well studied. Non-tricyclic
      antidepressants might be especially useful. Psychotherapy studies are virtually
      non-existent. CONCLUSIONS: Although dysthymia is considered a minor depressive
      condition, these findings show that it is a significant public health problem,
      comparable to major depression. Recent efforts to improve the recognition and
      treatment of major depression in medical settings, therefore, should be extended
      to include the entire spectrum of depressive disorders. Future studies should
      investigate the type and pattern of medical comorbidity and health care
      utilization, different antidepressant and psychosocial therapies, and the
      clinical and biological correlates of treatment response in different chronic
      depressive subtypes in medical settings and compare them to major depressive and
      subsyndromal depressive conditions.

PMID- 8270355
TI  - Should physicians screen for depression in elderly medical inpatients?: Results
      of a decision analysis.
AB  - OBJECTIVE: We wish to determine whether or not elderly medical inpatients should
      be screened for depressive disorder using either 1) a self-rated depression scale
      (Geriatric Depression Scale), 2) "usual clinical assessment," or 3) neither,
      assuming that treatment with tricyclic antidepressants (TCAs) is the primary mode
      of intervention. METHOD: Based on recent data from epidemiological studies on the
      prevalence and course of depression, the test characteristics of available
      screening tests, and the efficacy and side-effects of traditional
      antidepressants, decision analysis is used to help decide whether or not
      clinicians should screen for depression in this setting. RESULTS: These
      calculations indicate that if screening is done solely to identify depressed
      patients for treatment with TCAs, then the highest utility lies in not screening;
      however, the difference in utilities between that decision and the decisions to
      either screen with GDS or screen by usual clinical assessment was only .04 units
      on a 0 to 100 scale, making the decision virtually a toss-up. Furthermore, even a
      small variation in one of several clinical factors or test characteristics could
      give screening a higher utility. In particular, if psychotherapy is considered as
      the primary intervention, then the utility of screening exceeds that of not
      screening. CONCLUSION: Characteristics of the screening test, clinical setting,
      types and safety of available treatments, each impact on the usefulness of
      screening and must be kept in mind when diagnosing and treating depressed
      medically ill elders hospitalized in acute care settings.

PMID- 8270356
TI  - The patient-doctor relationship and metabolic control in patients with type 1
      (insulin-dependent) diabetes mellitus.
AB  - OBJECTIVE: Our hypothesis was that patient-doctor relationship experienced
      positively by the patient is associated with adequate compliance behavior and
      thus to the long-term metabolic control of diabetes. METHOD: Cross-sectional
      study of 100 consecutive adult patients with Type 1 diabetes treated in a
      diabetes out-patient department. From a questionnaire, four scores (direct
      estimate of physician, satisfaction with the place of treatment, self-esteem
      score, security with the patient-doctor relationship) determining the patient
      doctor relationship were formed. In score 3 (self-esteem score) the impact of the
      patient-doctor relationship to the patients' self-esteem was indirectly
      estimated. The anonymous data taken from diabetes register including information
      about treatment of diabetes, metabolic control and end-organ complications were
      returned together with the questionnaire. On the basis of GHbA1c diabetic
      patients were divided into two groups: with adequate metabolic control (GHbA1c <
      or = 8.0%) or with poor/moderate control (GHbA1c > 8.0%). RESULTS: In univariate
      analyses the score 3 associated with metabolic control (p < 0.001). In logistic
      regression analyses the nephropathy (t = 2.80, p < 0.05) and score 3 (t = 3.98, p
      < 0.001) were associated with metabolic control. CONCLUSION: Patient's positively
      experienced patient-doctor relationship was associated with good metabolic
      control of diabetes.

PMID- 8270357
TI  - Professionally-led support groups for cancer patients: an intervention in search
      of a model.
AB  - OBJECTIVE: The objective of this review was to evaluate the clinical and research
      literature on professionally-led support groups for cancer patients and to
      propose an approach that would address patients' needs from diagnosis through
      survivorship. METHOD: Computerized and manual searches, including Medline and
      Psychlit searches, were completed for reviews of the literature. Twelve research
      studies were identified that met our criteria for in-depth review. A clinical
      model emerged from discussions of an oncology study group based on theoretical
      formulations and clinical experience with oncology patients. RESULTS: We found
      that recent research suggests that professionally-led support groups are
      increasing in number and that participation in such groups seems to enhance
      patients' quality, and possibly even quantity, of survival. Despite this, little
      effort has been made to determine what type of group may be appropriate for which
      patients and when in their course of care. CONCLUSIONS: If psychosocial
      intervention, in the form of professionally-led support groups for cancer
      patients, is to be more effective, it should be guided by a model which takes
      into consideration the changing needs and concerns of patients over the course of
      illness and, in many cases, recovery. The authors present an outline delineating
      what such a model might entail.

PMID- 8270358
TI  - Psychologic distress as a longterm predictor of medical utilisation.
AB  - OBJECTIVE: To study baseline psychologic distress as a predictor of self-reported
      medical utilisation after nine years of follow-up. METHODS: in 1975-1978 we
      measured psychologic distress with a neuroticism scale in a general population
      sample of 826 women aged forty-five to sixty-four years. In the same study, and
      in a follow-up study nine years later, medical utilisation was quantified as the
      main outcome in terms of current treatment by a physician and current use of
      medication. RESULTS: The age and educational class adjusted odds ratio of
      baseline physician contact and use of medication for the upper versus the lower
      quintile of the neuroticism score were 3.3 (95% confidence interval (c.i.): 2.0
      5.2) and 3.6 (95% c.i.: 2.2-5.7), respectively. When the baseline neuroticism
      scores were related to utilisation at follow-up the adjusted odds ratios were 2.1
      (95% c.i.: 1.2-3.1) and 2.8 (95% c.i.: 1.8-4.5). However, in the subgroup of 352
      women who did not report initial medical utilisation the odds ratios were 1.1
      (95% c.i.: 0.5-2.4) and 1.4 (95% c.i.: 0.6-3.1). CONCLUSION: Although an
      association between psychologic distress and medical utilisation was confirmed,
      psychologic distress did not predict utilisation in middle-aged women
      characterised at baseline as non-utilizers.

PMID- 8270359
TI  - Psychiatric disorders in patients with Fabry's disease.
AB  - OBJECTIVE: To determine the frequency and etiology of psychiatric complications
      in patients with Fabry's disease. Method-Retrospective analysis and review of the
      records of thirty-three patients with confirmed Fabry's disease. RESULTS: Six
      patients (18%) developed psychiatric disorders. Five patients suffered depression
      and two of these patients committed suicide. One patient developed an acute
      confusional episode with subsequent development of behavioral changes as a
      complication of cerebrovascular disease. CONCLUSIONS: Psychiatric disorders, most
      commonly depression, complicate Fabry's disease and contribute to the morbidity
      and mortality of this disease.

PMID- 8270360
TI  - Early identification of hearing impairment in infants and young children.

PMID- 8270361
TI  - National Institutes of Health Consensus Development Conference Statement. Early
      identification of hearing impairment in infants and young children.

PMID- 8270362
TI  - The assessment of hypertrophy of nasopharyngeal tonsil by acoustical methods.
AB  - The possibilities for using acoustical analysis as a noninvasive measure of the
      degree of obstruction created by an enlarged pharyngeal tonsil (adenoid) are
      discussed. The method capitalizes on the relationship which exists between a
      specific obstruction of the respiratory tract and the resulting respiratory
      sound. Results indicate that as the adenoid increases in size relative to the
      size of the nasopharynx, the dominant components of the respiratory sound
      spectrum shift towards a higher frequency range. Furthermore, the correlation
      found between the assessments of the obstruction due to various sizes of the
      adenoid by radiological methods and acoustical analyses supports the theoretical
      prediction that information on the size of the constriction is carried by the
      respiratory sound. Therefore, careful analyses of the acoustic patterns in the
      respiratory sound can assist in identifying constrictions and monitoring the
      constriction changes in the upper respiratory tract.

PMID- 8270363
TI  - Serial measurements of transient evoked otoacoustic emissions (TEOAEs) in healthy
      newborns and in newborns with perinatal infection.
AB  - Detection of hearing impairment in early childhood is difficult. We serially
      recorded transient evoked otoacoustic emissions (TEOAEs) to search for signs of
      ototoxicity in term, healthy newborns and compared the results to a second group
      of term babies treated for perinatally acquired bacterial infection with
      ampicillin plus either cefotaxime or plus aminoglycoside. At initial evaluation,
      in the group of 45 healthy children born at term, well reproducible emissions
      were observed in all but two children. In each of these two, initially well
      reproducible TEOAEs were detected in one ear only. At the time of the second
      recording (mean at day 8.5) excellent emissions were seen in all ears of all
      children. Similarly, in the second group receiving ampicillin plus either
      cefotaxime or plus aminoglycoside, the height of emissions as well as TEOAE
      reproducibility was equal or even increased at the time of the second evaluation
      in all 17 patients. In the following group of 59 patients, all receiving
      ampicillin plus aminoglycoside, again TEOAEs were equal or improved at the time
      of follow-up examinations. In all patients, a reduced general condition tended to
      be associated with less reproducible TEOAEs. We conclude that at conventional
      doses in low-risk infants, aminoglycosides are unlikely to cause ototoxicity and
      that in early childhood serial TEOAE-recording may be useful for evaluation of
      inner ear function.

PMID- 8270364
TI  - Sensory organization of balance responses in children 3-6 years of age: a
      normative study with diagnostic implications.
AB  - The effect of altered sensory environments on balance was studied in 82 healthy
      children between 3 and 6 years of age. The purpose was to obtain normative
      measurements of postural stability during early stages of development for use in
      clinical posturography. Subjects were tested in three visual conditions (eyes
      open, blind-folded, and sway-referenced visual enclosure) during stance on either
      a fixed or sway-referenced force platform (EquiTest). During sway-referenced
      conditions, spontaneous changes in the subject's center of force (COF) drove
      rotational displacements of the platform and/or visual surround. The gain of
      platform/COF or surround/COF displacement was altered from 0.00 to 1.5. An
      equilibrium score (ES) was calculated based on the amount of postural sway
      compared to the maximum sway possible without falling. A higher ES reflected
      greater postural stability. An improvement in postural stability was observed
      between 4 and 5 years of development when the sensory environment was fixed (sway
      referenced gain = 0.0). In a dynamic sensory environment, however, age-related
      improvements in postural stability were not uniform and depended upon the
      specific sensory condition. For example, while 6 year olds generally showed the
      greatest postural stability of any age group, all ages showed statistically
      equivalent equilibrium scores during stance on a compliant surface with eyes
      closed, at all sway gains. The ability to ignore misleading sensory inputs to
      maintain balance was observed at 3 years of age; 76% of the 3 year olds (n = 16)
      were able to maintain stance in altered sensory environments at the 1.0 sway
      gain. In addition, postural stability was greater when visual inputs were sway
      referenced compared to conditions that manipulated the support surface
      compliance. These data suggest that the predominance of visual-vestibular control
      of balance gives way to a somatosensory-vestibular dependence by age 3, but that
      the transition to adult-like balance responses is not complete for all sensory
      conditions even by age 6. The use of posturography to enhance the assessment of
      pediatric vestibular and sensory integration deficits is discussed.

PMID- 8270365
TI  - Role of long-term stenting in treatment of pediatric subglottic stenosis.
AB  - Twelve cases of childhood subglottic stenosis diagnosed either acquired or
      congenital were treated using an endolaryngotracheal Montgomery T-tube. Stenting
      lasted on average 5.6 months. Tracheotomy closure was possible in 75% of cases on
      average 15.3 months after diagnosis. Tube-linked complications involved the child
      pulling out, forward migration of the tube out, lower tracheal migration of the
      tube, clogging and the formation of granulation tissue at its superior extremity.
      Comparison of outcomes with those for laryngeal surgery (cricoid split,
      laryngotracheal reconstruction) found in the literature, suggests that long-term
      T-tube stenting is the optimal treatment for subglottic stenosis where
      tracheomalacia precludes laryngeal surgery.

PMID- 8270366
TI  - Problems in the treatment of urinary infections caused by Streptococcus
      agalactiae.
AB  - Authors have investigated the therapeutic problems in urinary infections caused
      by Streptococcus agalactiae in men and nonpregnant women. It is obvious from the
      literature that this problem has been considered mainly in pregnant women. On the
      basis of 86 patients (67 women and 19 men aged 14 to 81 years) it was established
      that the in vitro sensitivity of this Streptococcus was high (above 95%) to
      ampicillin, augmentin, cephalothin, lincomycin, chloramphenicol and erythromycin
      and 100% to rifampicin. For a successful treatment it is of great importance to
      establish the presence or lack of reservoirs of this infection (vagina, urethra,
      gastrointestinal tract). Mono- and combined antibiotic therapy was applied, as
      well as local treatment with vaginal lavages. Successful treatment is guaranteed
      by a thorough examination, identification of infection foci, including those
      outside the urinary system and choice of adequate individual approach to the
      patient. These variants are presented in detail.

PMID- 8270367
TI  - Should radical nephrectomy include ipsilateral adrenalectomy?
AB  - We reevaluated 46 patients with histopathologically proven stage A and B renal
      cell carcinoma, who underwent radical nephrectomy for the presence of ipsilateral
      adrenal gland in the surgical specimens. It turned out that 23 specimens included
      ipsilateral adrenals. Two patients without adrenalectomy relapsed locally,
      whereas no local recurrence was noted in patients whose adrenals were removed.
      Three years' disease-free survival rates (DFS) for patients with and without
      adrenalectomy were 100% and 78%, respectively. Although no statistical difference
      was found in terms of DFS between patients with and without adrenalectomy, we
      suggest the removal of the ipsilateral adrenal gland if technically feasible.

PMID- 8270368
TI  - An unusual clinical presentation of non-Burkitt's lymphoma in a child. Case
      report.
AB  - A case of non-Burkitt's lymphoma (NBL) in a 31 months old female child is
      presented. Her kidneys were bilaterally enlarged. Although no abdominal mass was
      palpable, a sudden and unexpected bowel perforation has occurred. The diagnosis
      was established by autopsy studies. Because of its extremely rapid progression
      and in order to minimize the risk of life-threatening complications, children
      with non-Hodgkin's lymphoma (NHL) should be quickly and extensively evaluated.

PMID- 8270369
TI  - Use of a PCNL set for urinary stone removal from ureter, bladder and urethra.
AB  - A technique of urinary stone removal from ureter, bladder and urethra by means of
      a PCNL set is described. Results are excellent and the procedure seems to be
      simple.

PMID- 8270370
TI  - Voiding disorders and unstable bladder in children.
AB  - A total of 42 neurologically normal children with different voiding problems have
      been studied urodynamically during the last 4 years. Seventeen patients had
      unstable bladder, with significantly decreased capacity. The degree of volume
      decrease depended on the severity of instability and on the type of micturition
      problems. Eight patients had trabeculation of the bladder wall and 2 had wide
      bladder neck. Six children had vesicoureteral reflux in 8 ureters. Eleven
      patients were treated with Ditropan. Four children had repeated cystomanometry
      after treatment. They had stable bladder and its capacity has increased.

PMID- 8270371
TI  - Transvesical and transvaginal reparation in urinary vaginal fistulas.
AB  - Thirty-two cases of urinary vaginal fistulas treated surgically at our Department
      between 1985 and 1991 have been reviewed retrospectively. There were 26 cases of
      vesicovaginal fistulas, 1 case of urethrovaginal fistula and 5 cases of
      ureterovaginal fistulas. Gynaecological surgery was the leading cause of the
      fistulas (24/32). Eight cases of vesicovaginal fistulas and 1 case of
      urethrovaginal fistula were repaired transvaginally, with 88.8 per cent success.
      Seventeen cases of vesicovaginal fistulas were repaired by suprapubic
      transvesical approach, with 88 per cent success at the first attempt and 94 per
      cent success at 2 attempts. One patient with vesicovaginal fistula underwent
      ureterosigmoidostomy. Ureterovaginal fistulas were repaired successfully by
      simple ureteroneocystostomy in 4 cases and 1 case of ureterovaginal fistula
      required ureteric substitution with a Boari bladder flap.

PMID- 8270372
TI  - An alternative technique for ureterocolonic anastomosis: ten years of experience.
AB  - We present an alternative technique of ureterocolonic anastomosis which has been
      standardized at our Department since 1981. Early and late postoperative
      complications of 82 patients who underwent ureterosigmoidostomy are reviewed.
      Urinary leakage was observed in 3 patients (3.7%) in the early postoperative
      period. Late complication rate in 38 patients, whose data concerning
      postoperative course could be obtained, was found to be 15.8%. Mean follow-up was
      38.5 +/- 10.2 months. Long-term results were comparable with those in the
      literature and it has been proved to be a simple and satisfactory technique of
      ureterocolonic anastomosis.

PMID- 8270373
TI  - Incidence of anal incontinence after long-term follow-up of patients treated by
      ureterosigmoidostomy.
AB  - Twenty-eight patients who had been treated with ureterosigmoidostomy after
      radical cystectomy were examined with special reference to anal incontinence. In
      the present series, 17 out of 28 patients (60.7%) had daytime and/or nighttime
      anal incontinence. In these patients preoperative function of the external and
      sphincter was considered to be sufficient. Anal incontinence occurred immediately
      after operation in only 3 patients. Incontinence emerged at an average duration
      of 2.6 years after ureterocolonic anastomosis. Incidence of anal incontinence
      after ureterosigmoidostomy appeared to be influenced by aging.

PMID- 8270374
TI  - Effect of continuous irrigation with normal saline after prostatectomy.
AB  - Normal saline solution is often used for continuous irrigation of the bladder
      following prostatectomy in order to prevent clot retention. There is usually a
      concern for possible sodium reabsorption and consequent fluid retention.
      Considering the harmful cardiovascular effect in elderly patients who usually
      come for prostatectomy, fluid retention could be detrimental. Therefore we have
      hitherto given daily lasix injections routinely during continuous irrigation of
      the bladder with normal saline solution. This study is designed to find out if
      the amount of sodium reabsorbed is significant enough to justify the practice.
      The amount reabsorbed is indeed not significant (p > 0.05). A plea is therefore
      made to give lasix injection following prostatectomy only if there is a clinical
      indication for it.

PMID- 8270375
TI  - Hormone chemotherapy for newly diagnosed patients with metastatic prostate
      cancer.
AB  - From 1981 to 1989, 24 patients with newly diagnosed metastatic prostate cancer
      received hormone chemotherapy consisting of orchiectomy, diethylstilbestrol
      diphosphate and cisplatin. The survival rates were compared with those of 17
      metastatic prostate cancer patients who were treated with hormone therapy alone.
      The five-year survival rates for the hormone chemotherapy group and the hormone
      therapy group were 64.6% and 29.4%, respectively. Based on our findings, it seems
      likely that hormone chemotherapy is one of the most effective treatments for
      patients with newly diagnosed metastatic prostate cancer.

PMID- 8270376
TI  - Very rare angioleiomyoma of the male urethra.
AB  - Herein is reported a case of angioleiomyoma, i.e. a benign tumour arising
      predominantly from smooth muscle cells of the vessel wall, in a yet unreported
      locality, the urethra. The closest to the tumour presented by us are leiomyomas
      of the urethra, so far described only in females. The angioleiomyoma of our case
      manifested itself as a stricture of the male urethra and resection operation
      showed to be the best approach with elimination of the patient's complaints.

PMID- 8270377
TI  - Semen samples with teratozoospermia show a lower percentage of spermatozoa with
      detectable adhesion molecules (AM).
AB  - Adhesion molecules (AM) are cell surface proteins which interact with ligands and
      mediate cell-cell bindings. Possibly, the AM are involved in the spermatozoal
      adhesion to oocytes. Human spermatozoa showed several adhesion molecules on their
      surface: the alpha chains of the beta 1-integrins VLA alpha 4 (CDw 49d), VLA
      alpha 5 (CDw 49e) and VLA alpha 6 (CDw 49f), the beta-chain of beta 2-integrins
      (CD 18) and the matrix proteins laminin and fibronectin. Semen samples with
      severe teratozoospermia were characterized by a significantly lower percentage (P
      < 0.01) of spermatozoa with VLA alpha 4, VLA alpha 5 and laminin. VLA alpha 5
      (the alpha-chain of the fibronectin receptor) showed the most significant
      difference between the "normal" and teratozoospermic semen sample groups. This
      phenomenon could contribute to the explanation of a lower fertilizing capacity of
      teratozoospermic semen samples.

PMID- 8270378
TI  - Experimental testicular ischaemia: time course of the effect on rat
      spermatogenesis.
AB  - Protection of the spermatogenic cells against anticancer drugs can be performed
      by temporarily interrupting testicular blood flow during drug administration. In
      our study we investigated the effect of ischaemia on spermatogenesis, using
      mature male Sprague-Dawley rats. Eight and 16 weeks after a 1 h period of left
      testicular ischaemia, left testicular weights significantly decreased compared
      with the controls (both, p < 0.05). The decreased testicular weights returned to
      almost normal values at 24 weeks. Sperm counts in the left cauda epididymis were
      significantly reduced 8, 16 and 24 weeks after ischaemia (p < 0.01, p < 0.01 and
      p < 0.05, respectively). Sperm motility also decreased 8 and 16 weeks after the
      procedure (both, p < 0.01). These parameters returned to normal at 48 weeks. The
      diameter of seminiferous tubules in the left testis was diminished 8 and 16 weeks
      after testicular ischaemia, and increased tubular wall thickness on the left side
      was demonstrated 8 weeks after ischaemia (each, p < 0.05). No changes in the
      parameters at any interval after ischaemia were observed in the right testis. The
      serum levels of LH, FSH and testosterone showed no alteration throughout the
      experiment. The present study reveals that testicular damage induced by ischaemia
      up to 1 h is completely reversible and no contralateral orchiopathy is produced
      by this procedure.

PMID- 8270379
TI  - Tight heparin regimen for haemodialysis in children.
AB  - Various methods of anticoagulation have been described in patients with increased
      risk for haemorrhage. In this study we have tried to define the lowest dose that
      would allow the completion of dialysis in uraemic patients with bleeding risks. A
      total of 51 procedures were completed with a dose of 15 IU/kg body weight per
      hour in seven children. With this dose the PTT and Lee-White clotting time were
      kept in the desired range and no complications occurred. We suggest that low-dose
      continuous heparinization is a safe and cheap technique in these patients.

PMID- 8270380
TI  - Effect of haemodialysate and its peptide fractions on acetylcholinesterase
      activity in erythrocytes from healthy subjects and patients with terminal renal
      failure.
AB  - The effects of haemodialysate and its three peptide fractions on
      acetylcholinesterase (AChE, E.C. 3.1.1.7) activity in erythrocytes from healthy
      subjects and patients with terminal renal insufficiency treated by repeated
      haemodialyses have been studied. It was shown that erythrocytes from
      haemodialysed patients display an increased activity of the enzyme if compared
      with those from healthy subjects. Neither haemodialysate nor any of its three
      peptide fractions, when incubated with erythrocytes from healthy subjects and
      from haemodialysed patients, have altered the activity of the enzyme, except for
      fraction III at the highest concentration. This fraction exerted an inhibitory
      effect on AChE activity of the erythrocyte derived from healthy subjects.

PMID- 8270381
TI  - Clinical aspects of renal involvement in Bardet-Biedl syndrome.
AB  - The Bardet-Biedl syndrome (BBS), which consists of polydactyly, obesity, mental
      retardation, pigmentary retinopathy and hypogonadism has been known since 1922,
      but due to the great similarity to the clinical manifestations of the Laurence
      Moon syndrome (LMS) there is a considerable terminological confusion in the
      medical literature. An attempt is made at clarifying the problem. Four children
      from two families have been observed. There were inter- and intrafamilial
      variabilities of the expression and severity of the particular features, but
      retinopathy and structural and/or functional abnormalities were found in 100%.
      The combination of the two can serve as an easy clinical screening for diagnosis
      of the disease. Renal involvement is considered to be a cardinal feature of the
      syndrome. The most common and earliest symptoms are polydypso-polyuria and
      reduced concentrating ability, which may lead to some diagnostic difficulties,
      especially in infancy. Three children have end-stage renal disease and two of
      them are on maintenance haemodialysis, which they tolerate well.

PMID- 8270382
TI  - Repair of newly condensed amalgam restorations.
AB  - This study investigated the tensile strength of the newly condensed amalgam
      repaired with newly triturated amalgam in different times. A separable plexiglass
      mold with a dumbbell shape "cavity" was prepared. Amalgam was condensed in the
      "cavity" and allowed to set for one hour before it was removed from the mold and
      used for control. Five controls were prepared. Five groups with five samples in
      each group were prepared. Amalgam was condensed in the first half of the "cavity"
      and 5, 15, 30, 60 minutes and 24 hours later newly triturated amalgam was
      condensed in the second half of the "cavity" for the 5, 15, 60 minutes and 24
      hour group samples. All samples were allowed to set in the mold for one hour then
      removed and stored in 100% humidity condition at room temperature for 24 hours.
      Tensile strength was tested on the Instron testing machine. It was found that
      when the newly condensed amalgam was repaired in five minutes, it has 84% of the
      tensile strength and was not significantly different from the controls. When it
      was repaired in 15, 30, 60 minutes and 24 hours, the tensile strength was
      significantly lower than the controls and significantly different from the
      controls.

PMID- 8270383
TI  - Dental technology and the Good-Old-Days ethics.

PMID- 8270384
TI  - Post-traumatic stress disorder: a biopsychological perspective.
AB  - This paper provides a critical review of the current explanatory models of the
      post-traumatic stress disorder (PTSD). Most of these models are incomplete and
      lack empirical confirmation. It is argued that unidimensional treatment
      modalities, derived from such models, fail to address the complex nature of the
      disorder and are likely to generate partial results. A broad hypothesis-testing
      approach, combining biological, psychological and psychosocial interventions,
      should be preferred in clinical practice. Rehabilitation should replace curative
      techniques and unrealistic goals in many cases.

PMID- 8270385
TI  - Assessment of PTSD: validation of the revised PTSD Inventory.
AB  - The PTSD Inventory, a self-report diagnostic questionnaire based on DSM-III
      criteria, was revised to meet the more recent DSM-III-R criteria. This study
      examined the validity of the revised inventory relative to a structured clinical
      interview (SCID) and the Impact of Events Scale (IES). Results showed a high
      degree of concordance between the instruments, supporting the use of the more
      standardized, easy to administer and economical PTSD Inventory.

PMID- 8270386
TI  - Point of view: alcoholic physicians in Israel.
AB  - Data on alcohol drinking habits among medical students and levels of alcoholism
      in the general population imply that there are a significant number of alcoholic
      physicians in Israel. The tendency of the alcoholic doctor to conceal, the
      tendency of colleagues to deny and protect, and the inadequate education on the
      effects and consequences of alcohol dependence among physicians in Israel are
      presented as explanations for the absence of reporting of this phenomenon.

PMID- 8270387
TI  - Reform in the Israeli health care system.

PMID- 8270388
TI  - Mental health services in Israel: current state and future directions.
AB  - This paper reviews the current state of Israel's mental health system during a
      period when it may be possible to bring about significant change. It analyses its
      strengths and weaknesses, including the heavy influence of the psychiatric
      hospital and the lack of necessary community programs. The author stresses the
      need for an integrated planning process, based upon a vision of what the mental
      health system should look like and who it should be serving, and discusses how
      this process could occur.

PMID- 8270389
TI  - The Israeli mental health budgeting policy: an historical perspective.
AB  - The Israeli health care system is undergoing important and drastic changes. The
      two main causes, the State Commission of Inquiry into the Functioning and
      Efficiency of Health Care Report and the Ministry of Health National Health Law,
      are publicly discussed. One of the main changes will be the mental health care
      budgeting system. This paper summarizes the current reimbursement policy and the
      main budgeting models of psychiatric services. It also reviews the main changes,
      in a historical perspective, of the psychiatric services organization.

PMID- 8270390
TI  - The velvet reform of the British medical services: implications for Israeli
      psychiatry.
AB  - Since 1990, the United Kingdom has been reforming its public medical services
      aiming at decentralization and more competition among the providers of services.
      To achieve these aims two major administrative changes are being introduced: a)
      increased direct cooperation between providers and consumers; b) the creation of
      self-government trusts (similar to the Israeli "taagidim"). Israel is also
      modifying the structure of its medical services in ways which have some basic
      similarities to the U.K.'s changes. However, the British process of change is
      smoother and steadier. The possible effects of the general changes on the
      psychiatric services in the U.K. and in this country are complex and are already
      raising controversies. This paper compares the processes in both countries.

PMID- 8270391
TI  - Defrocking the fraud: the detection of malingering.
AB  - The purpose of this paper is to provide psychiatrists with practical advice on
      how to detect malingered mental illness. Various types of malingering are defined
      and the five major purposes of malingering are specified. The research literature
      on malingering is reviewed. Clinicians must be thoroughly grounded in the
      phenomenology of true mental disease to detect malingering. Detailed information
      about hallucinations is reviewed so that faked hallucinations that do not follow
      typical patterns can be more easily identified. Strategies for approaching
      persons suspected of malingering are suggested. Features of malingered mutism,
      mania, depression and mental retardation are described. The differential
      diagnosis of malingering, post-traumatic stress disorder, conversion disorder,
      and post-concussion syndromes after trauma is discussed. Clues to malingered
      psychoses and post-traumatic stress disorders are delineated. Finally, specific
      indicators of malingered insanity defenses are identified.

PMID- 8270392
TI  - Cefuroxime prophylaxis in biliary surgery: single versus triple dose.
AB  - The standard regimen for prophylaxis in bilary surgery consists of three doses of
      a first- or second-generation cephalosporin (one pre- and two postoperatively).
      The purpose of our study was to compare a single dose of cefuroxime (1.5 gi.v. on
      call to surgery) with the standard regimen (1.5 gi.v. on call to surgery followed
      by two additional doses of 750 mg i.v. each, 8 and 16 h after surgery). One
      hundred patients participated in the study, 44 in the single-dose group and 56 in
      the triple-dose group. These two groups did not differ with regard to sex, risk
      factors, duration of surgery, etc. The incidence of infection was 9% in the
      single-dose group and 7% in the triple-dose group. We conclude that one dose of
      cefuroxime is as effective as three for biliary surgery. This regimen would
      reduce the risk of side effects and/or suprainfections and the emergence of
      resistant strains of bacteria. It is also more convenient for the nursing staff
      and reduces the cost by one-half.

PMID- 8270393
TI  - Extracorporeal shock wave lithotripsy of gallstones: early experience in an
      Israeli population.
AB  - Fifty-four patients with symptomatic gallbladder stones were treated by extra
      corporeal shock wave lithotripsy (ESWL) and oral bile acids on an outpatient
      basis. In 49 patients (90%), the stones were successfully fragmented to fragments
      < 5 mm on follow-up ultrasonography. Patients underwent 1-3 lithotripsy sessions
      with 7,500-9,750 shock waves per session. The gallbladder clearance rate of
      fragments was dependent mainly on the number of stones and reached 59% for
      patients with one or two stones, compared to 34% for patients with more than two
      stones after 9 months follow-up. The only side effects noted were mild abdominal
      pain, transient microscopic hematuria and minimal impairment in liver function
      tests. There were no serious complications such as cholecystitis, bile duct
      obstruction, or pancreatitis. These results, which are comparable with those of
      other groups using the same shock wave lithotriptor, indicate that this therapy
      may become an alternative treatment for selected patients with symptomatic
      gallbladder stones, especially those who are at high risk for surgical treatment.

PMID- 8270394
TI  - Management of gallstone ileus--a controversial issue.
AB  - Four cases of gallstone ileus were treated during a 3-year period. Three patients
      aged 74-81 years underwent a one-stage operation consisting of enterotomy, stone
      extraction, cholecystectomy, and suturing of the entero-biliary fistula. One 83
      year-old patient was considered a poor risk and underwent only enterotomy with
      stone extraction, without cholecystectomy. In all four patients the postoperative
      course was uneventful. In one, carcinoma of the gallbladder was found. On the
      basis of this experience as well as that reported in the literature, it is
      concluded that the procedure to be preferred in stabilized patients is a one
      stage operation, whereas in debilitated patients only relief of the obstruction
      should be sought.

PMID- 8270395
TI  - "Pantaloon" phytobezoar: an unusual cause of intestinal obstruction associated
      with Meckel's diverticulum.
AB  - An unusual cause of small bowel obstruction associated with Meckel's diverticulum
      is described in two boys, aged 10 and 11 years. The causal factor was a
      phytobezoar lodged in the diverticulum in a Y-shaped "pantaloon" fashion.

PMID- 8270396
TI  - Problems in the surgical management of sclerosing encapsulating peritonitis.
AB  - Sclerosing encapsulating peritonitis (SEP) is a rare complication of chronic
      ambulatory peritoneal dialysis. Although commonly involving the small bowel and
      associated with severe surgical complications, this entity has almost never been
      mentioned in the surgical literature. We report here another case of severe SEP
      and briefly discuss its surgical implications.

PMID- 8270397
TI  - A new diagnostic test for incomplete vagotomy: experimental study in dogs.
AB  - Despite the decline in the number of operations for intractable duodenal ulcer
      disease, there are still many patients who suffer from the side effects of
      vagotomy. Incomplete vagotomy may be a significant cause of surgical treatment
      failure. Diagnosis of incomplete vagotomy is not easy since there is no reliable,
      safe, single test available for this purpose. We hypothesized that incomplete
      vagotomy can be made temporarily complete in response to a muscarinic blocking
      agent. A gastric cannula was inserted and vagotomy performed in 12 female dogs,
      which was incomplete in 6 and complete in 6 dogs. Gastric acid secretion was
      stimulated for 2 h with i.v. pentagastrin at a rate of 6 micrograms/kg per h.
      After the first hour 6 mg/kg pirenzepine (M1 muscarinic receptor antagonist which
      may block the effect of intact vagal fibers on postganglionic submucosal neurons)
      was added i.v. In the complete vagotomy dogs there was no significant decrease in
      gastric output rate: 12.28 +/- 4.06 mEq/h in the first hour, and 12.00 +/- 3.80
      mEq/h in the second hour (mean +/- SE, P = 0.963, t = 0.048). In the incomplete
      vagotomy dogs a significant decrease in gastric acid output rate was observed:
      10.19 +/- 1.10 mEq/h in the first hour, and 4.33 +/- 0.95 mEq/h in the second
      hour (mean +/- SE, P = 0.002, t = 4.029). We conclude that a
      pentagastrin/pirenzepine test may differentiate between complete and incomplete
      vagotomy in the dog.

PMID- 8270398
TI  - Balloon aortic valvuloplasty in the elderly: useful when there is no alternative.
AB  - Of 63 elderly patients with calcific aortic stenosis in whom balloon aortic
      valvuloplasty was performed, 26 treated with the new technique of Cribier and
      Letac are the subject of this report. Patients were referred for the procedure
      because they were at high surgical risk, or were not candidates for surgery.
      Seven matched patients who fit the criteria for balloon valvuloplasty but refused
      the valvuloplasty procedure served as controls. Aortic gradient decreased from 78
      +/- 27 mm Hg to 35 +/- 20 mm Hg and aortic valve area increased from 0.47 +/-
      0.16 cm2 to 0.83 +/- 0.38 cm2 (P < 0.0001). Symptomatic improvement was
      immediately obtained in each patient. Complications were rare, with only one
      patient needing vascular repair for femoral artery occlusion. Three patients died
      during the initial hospitalization (none during the procedure). Valvuloplasty
      patients were followed for a mean period of 9.6 +/- 9.4 months. Three months
      survival was 87%, 6 months survival was 76%, and 12 months survival was 61%. Four
      of seven patients in the control group (57%) died within 3 months after initial
      referral. Balloon aortic valvuloplasty is a useful treatment in elderly patients
      who are poor surgical candidates. It may have a positive influence on short-term
      survival.

PMID- 8270399
TI  - Percutaneous balloon aortic valvuloplasty--a third alternative.

PMID- 8270400
TI  - Preliminary experience with intraoperative angiography using the Kelly inflatable
      T-tube--an advantageous procedure in urgent embolectomies.

PMID- 8270401
TI  - Successful outcome of a left ventricular free wall rupture in a community
      hospital: case report.
AB  - Rupture of the myocardium in the setting of acute myocardial infarction has a
      universally grim prognosis. The time that elapses between diagnosis and
      definitive therapy is the most critical determinant of the patient's outcome when
      death is not instantaneous. Survivors of this catastrophic event have not been
      frequently reported. We present a case of free wall left ventricular rupture in a
      patient with an acute myocardial infarction hospitalized in the Cardiac Care Unit
      of a small community hospital. The patient was successfully transferred to the
      referral institution for surgery. Rapid diagnosis, primary bedside therapy, and
      utilization of new surgical techniques helped obtain a good outcome.

PMID- 8270402
TI  - Tricuspid valve surgery: recent experience at the Chaim Sheba Medical Center.
AB  - From 1 January 1989 to 30 June 1992, 35 patients underwent cardiac surgery that
      included a tricuspid valve (TV) procedure. All had severe TV dysfunction
      documented by echocardiography, and were in NYHA functional class III-IV. The
      etiology of TV dysfunction was rheumatic-functional in 19 patients, rheumatic
      organic in 13, and infective in 3. Nineteen (54%) had had at least one previous
      cardiac operation, and in 29 an associated procedure (MVR, AVR, DVR, DVR + CABG)
      had been performed. The TV was repaired in 27 patients, was replaced by a
      bioprosthesis in 7, and was excised in 1. There were three (8.6%) operative and
      two late deaths. Except for two, all surviving patients are in NYHA functional
      class I-II. In two patients with organic lesions who underwent repair, residual
      moderate tricuspid regurgitation was observed. We conclude that in these
      critically ill patients TV surgery can be performed with acceptable results. Long
      term fate of a bioprosthesis in the tricuspid position is yet to be determined.

PMID- 8270403
TI  - Intra-arterial thrombolytic therapy: a combined approach with angioplasty and/or
      minor surgery.
AB  - Low-dose intra-arterial treatment was performed in 124 patients who underwent a
      total of 142 procedures. The series included 87 occluded arteries and 55 occluded
      grafts. In only 29 instances (21%) was thrombolysis alone sufficient. In another
      77 procedures (54%) the thrombolysis was followed by either angioplasty or minor
      surgery. In the remaining 36 treatments (25%) lysis of the occlusion failed. A
      successful end result of combined treatment was achieved in 67 of 77 (87%)
      procedures. Including the 29 patients in whom thrombolysis alone sufficed, a
      total of 96 of the 142 procedures (67%) were successful, with the overall success
      rate being better in grafts (78%) than in arteries (61%). The suprainguinal
      lesions had a significantly better response compared to the infra-inguinal ones.
      The evaluation of all procedures was done at the time of discharge from hospital.
      Complications were related either to local or systemic hemorrhage or distal
      embolization. Death related to treatment occurred in three patients.

PMID- 8270404
TI  - Intracerebral hemorrhage in an infant with idiopathic thrombocytopenic purpura:
      approach to the surgical management.
AB  - We describe a 21-month-old female infant with severe idiopathic thrombocytopenic
      purpura (ITP), who presented in coma with signs of cerebral herniation. CT scan
      revealed a right temporo-parietal intracerebral hemorrhage. The patient underwent
      immediate craniotomy and the hematoma was drained. Marked improvement in her
      neurological status, as well as postoperative resolution of the intracranial
      hemorrhage, were noted. Three months after the operation she recovered from the
      ITP. We emphasize the option of performing craniotomy without splenectomy in ITP
      infant patients.

PMID- 8270405
TI  - Coronary artery bypass without cardiopulmonary bypass--the pros and the cons.

PMID- 8270406
TI  - Bilateral asynchronous renal cell carcinoma: treatment approach.
AB  - Two hundred patients underwent nephrectomy for renal cell carcinoma (RCC) at our
      service in 1978-89. During follow-up four patients developed RCC in the remaining
      kidney and underwent a parenchymal preserving procedure as curative treatment
      (one enucleation, and three partial nephrectomies). The interval between the
      nephrectomy and the diagnosis of asynchronous RCC was 50-84 months (mean 65
      months). None of the patients needed dialysis after the operation, and creatinine
      level in all remained between 1.6 and 1.9 mg. One patient died from a heart
      attack 8 years after the partial nephrectomy, two patients have no evidence of
      disease 24 months and 76 months after enucleation and partial nephrectomy,
      respectively. The fourth patient, who had resection of metastatic lesion in the
      scalp 36 months before the partial nephrectomy, is alive 34 months after the
      procedure but has lately developed recurrence in the scalp. Although relatively
      rare, it is important to be aware of the possible asynchronous development of RCC
      in the contralateral kidney after nephrectomy for RCC. In such cases, parenchymal
      preserving procedure (enucleation, partial nephrectomy) is an alternative that
      should be considered to improve the quality of life and to avoid the need for
      dialysis.

PMID- 8270407
TI  - Subtotal colectomy with primary ileocolonic anastomosis for obstructing carcinoma
      of the left colon: valid option for elderly high risk patients.
AB  - During a period of 4 years, 20 patients with obstructing carcinoma of the left
      colon were treated by subtotal colectomy with primary ileocolonic anastomosis.
      Thirteen patients (65%) were 65 years of age or older. All patients presented to
      the emergency room with large bowel obstruction. Twelve patients (age > 65)
      suffered other systemic diseases (chronic obstructive pulmonary disease, ischemic
      heart disease, morbid obesity), placing them in a high risk category. The
      mortality rate was 5% (1/20), 7.6% if only high risk patients are considered. The
      one-stage procedure in the treatment of obstructing carcinoma of the left colon
      offers the patient a number of advantages over stage intervention elimination of
      colostomy, namely removal of occult lesions in the resected colon, shorter
      hospitalization and low morbidity and mortality. We found this procedure to be a
      valid option also in the elderly (> 65) high risk patient. Metastatic disease in
      our view is not a contraindication, since the elimination of colostomy will
      improve the quality of life of these patients.

PMID- 8270408
TI  - Carcinoma of the colon in youngsters: a report of three cases.
AB  - Three youngsters aged 12, 16, and 18 years underwent surgery for carcinoma of the
      colon, a very rare occurrence in this age-group. In all three patients the
      prominent feature was a marked delay in diagnosis and treatment, as reflected in
      the advanced pathological stage of the tumors (Dukes' C and D). An increased
      awareness of the possible occurrence of this type of tumor in young patients, and
      the resultant earlier diagnosis, are the only means for improving the prognosis.

PMID- 8270409
TI  - Primary appendiceal neoplasms.
AB  - A retrospective review of the files of 1,740 appendectomies performed during a 10
      year period disclosed 13 patients (0.7%) with primary appendiceal tumors.
      Adenocarcinoma of the appendix was diagnosed in 6 patients (0.3%), which is a two
      to four-fold higher incidence than reported in the literature. The other seven
      patients had benign tumors and only appendectomy was performed. The female to
      male ratio of adenocarcinoma was 5:1. All six adenocarcinoma patients, classified
      histologically as Dukes' B stage, underwent right hemicolectomy, and were disease
      free following a mean follow-up of 35 months. The results of our policy, also
      recommended by others, confirmed the benefit of right hemicolectomy in all
      patients with confirmed primary appendiceal carcinomas.

PMID- 8270410
TI  - Radial forearm free flap in head and neck reconstruction.
AB  - The use of the radial forearm free flap, otherwise known as the "Chinese" flap,
      to provide reconstruction of large ablative defects of the face or oral lining is
      reported in three patients. Microvascular anastomosis was used to ensure flap
      viability. This donor site was found to be especially versatile because it
      enables the transfer of skin areas of a variety of sizes and because the thin
      pliable nature of the forearm skin is well suited to replace oral mucosa. Part of
      the radius and muscles may also be included in the flap.

PMID- 8270411
TI  - Contraceptive surgery and breast tumors in mice.
AB  - The effect of contraceptive surgical manipulations on mammary gland changes was
      investigated in mice models. Total hysterectomy with bilateral adnexectomy,
      bilateral tubal ligation, unilateral tubal ligation and moderate uterine
      compression were performed in various subgroups of 500 mice. Mammary gland tumors
      (adenomas, adenocarcinomas, squamous cell carcinomas) were observed in an average
      of 50% (between 20 and 66%) of the operated animals about 6 months after surgery,
      while the controls remained free of tumors. Surgical interference with the
      reproductive capacity seems to have an effect on the mammary glands, inducing
      neoplastic changes. The relationship of our results to the influence of
      contraceptive procedures on the appearance of mammary gland tumors in women is
      discussed.

PMID- 8270412
TI  - Filtering surgery with 5-fluorouracil subsequent to Molteno implant.
AB  - In cases of refractory glaucoma, when Molteno shunt implantation has been
      performed and resulted in failure, the best surgical option has not yet been
      established. Filtering surgery with 5-fluorouracil (5-FU) as one option for the
      above was performed in four non-neovascular glaucomatous eyes (four patients)
      after failure of Molteno shunt implantation. Injections of 5 mg 5-FU were
      administered once daily for 9-14 days. After follow-up of 6-18 months in 3 eyes,
      intraocular pressure ranged from 10 to 16 mm Hg. In the fourth eye, in which bleb
      scarring ensued, a second filtering surgery with 5-FU was performed after 4
      months, and resulted in a successful outcome as recorded 26 months later. These
      preliminary results suggest that filtering surgery with 5-FU might be an
      acceptable surgical option in non-neovascular refractory glaucoma subsequent to
      failure of Molteno shunt implantation.

PMID- 8270413
TI  - Significant recent advances in the treatment of osteogenic sarcoma.

PMID- 8270414
TI  - Arsenic toxicity in Hawaii: a case report and review.
AB  - As mentioned at the beginning of this article, many questions were raised in our
      one particular case including the problem of verifying true arsenic toxicity and
      in determining the source of the exposure. In our case, there was a markedly
      elevated concentration of arsenic in samples of pubic hair and in the sample of
      urine. While arsenic toxicity can present with GI symptoms, we felt that in this
      particular case the association of the abdominal pain with arsenic toxicity was
      unlikely. For one, the patient's symptoms persisted despite apparent adequate
      treatment for arsenic toxicity. Also, the usual symptom of chronic arsenic
      toxicity is peripheral neuropathy (which was not documented in our case) and not
      abdominal pain. After the exhaustive diagnostic workup, we felt that this patient
      had irritable bowel syndrome and that the discovery of arsenic toxicity was
      serendipitous. In regards to the etiology of the toxicity, the patient's
      occupation involved working in the construction industry for a number of years.
      He indicated a definite exposure to termite-treated wood throughout that period.
      Wood for building houses, etc. is commonly pressure-treated with an arsenic-based
      compound; therefore, this source of occupational exposure appears to be a likely
      one. Another remotely possible source was the ingestion of contaminated illicit
      drugs. Cases of the use of illicit drugs laced with various toxic agents such as
      cyanide and strychnine have been reported. Although our patient required
      analgesics not commensurate with his symptoms, he categorically denied any use of
      "street" drugs. The random urine drug screen for such was negative.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8270415
TI  - Thrombocytopenia associated with exposure to iodine.

PMID- 8270416
TI  - Tears of Hippocrates/go gently.

PMID- 8270417
TI  - A smoking cessation pilot program.
AB  - National health-care costs are continuing to climb and employers in Hawaii and
      across the nation are forced to increase their share of the burden. To limit
      these costs, worksite health promotion programs are increasing in number and in
      scope. Smoking control programs in particular now rank as the most prevalent type
      of worksite program; as the disability, absenteeism, and early death on the part
      of smokers have been well-documented as contributing to the cost of health care.
      Our research describes a year-long, pilot smoking-cessation program implemented
      at Hawaiian Telephone Company. Our program used a combination of behavioral
      modification, social support and incentives technique to assist people to stop
      smoking or to maintain their nonsmoking behavior. The 12 volunteer participants
      provided a multiethnic, long-term, heavy smoker employee sample. Survey results
      at 1 year demonstrated that 4 of them quit smoking (quit rate = 50%), 2 reduced
      their tobacco intake, 2 dropped out of the program and continued to smoke. The 4
      who had entered the program for maintenance purposes remained smoke-free. Cost
      benefit analysis yielded conservative estimates indicating that the program had
      paid for itself and saved an additional $350 a year per participant who remained
      a nonsmoker.

PMID- 8270418
TI  - Vibrio in stinging seaweed: potential infection.
AB  - Toxic strains of the finely filamentous, velvety, dark-olive green to black algal
      organism, Microcolus Lyngbyaceus, (formerly Lyngbya majuscula Gomont, or
      "lyngbya") have been recognized as etiologic agent of "stinging seaweed"
      dermatitis (one of several forms of "swimmer's itch") in Hawaii since the late
      1950s as reviewed. Lymphadenopathy, pustular folliculitus, and local infections
      have been reported in some persons.

PMID- 8270419
TI  - Insurance status and access to health services among poor persons.
AB  - OBJECTIVE: We examine the relationship between health insurance status and access
      to care among low-income persons 65 years of age and under, taking into account
      their social demographic characteristics and health care needs. DATA SOURCES AND
      STUDY SETTING: Study groups consist of the subsamples of persons with incomes
      between 100 and 150 percent of the federal poverty level and those below the
      federal poverty level interviewed in the 1983, 1984, and 1986 Health Interview
      Surveys (HIS) of the National Center for Health Statistics. Sample sizes range
      from about 6,000 to 11,000 depending on the proportion of each study group
      administered the insurance supplement. STUDY DESIGN: Annual visits and whether
      hospitalized during a year are used as measures of access to medical care. The
      analysis consists of identifying predictors of use of services (i.e., health
      status and social characteristics) and, taking them into account, examining the
      relationship of insurance status to access to care. This was first undertaken on
      the 1983 survey; the models obtained then are replicated on the other two years
      of data. DATA COLLECTION/EXTRACTION METHODS: The HIS utilizes in-person
      interviews to gather health and medical history information from a stratified
      random sample of the U.S. population. Data were obtained through public use tapes
      distributed by the National Center for Health Statistics. PRINCIPAL FINDINGS:
      Results are consistent for all three years among persons in poverty. Being
      covered by Medicaid, in contrast to having private insurance or being without
      health insurance, is related to use of both ambulatory care and hospital care.
      The access differences for persons in poverty, regardless of their vulnerability
      or "risk" of requiring medical care, are marked and generally statistically
      significant. Among the near-poor the same findings occur, although the
      differences are less sharp and less often statistically significant. CONCLUSIONS:
      The most obvious explanation is that the poor, and to a considerable extent the
      near-poor, have limited access because of copayments and deductibles that are
      typically part of private insurance coverage. The findings raise policy questions
      regarding the utility of either "play or pay" employer-provided insurance or
      income tax deductions to increase access.

PMID- 8270420
TI  - The use of health services by women with HIV infection.
AB  - OBJECTIVE: The purpose of this study is to determine whether women who have been
      diagnosed with HIV utilize the same volume of medical care services as men who
      have been diagnosed with HIV. DATA SOURCES: This study uses data from the first
      wave of interviews of the AIDS Cost and Service Utilization Survey (ACSUS)
      conducted between May and July of 1991. The first wave of interviews involved
      1,949 adults and adolescents, of whom 359 were women. STUDY DESIGN: The ACSUS
      sample was selected from 26 sites (hospitals, clinics, and physician offices) in
      ten cities chosen from the 25 cities with the most AIDS cases. Cities are located
      throughout the nation, and in low, medium, and high prevalence areas. The sites
      in each city are generally those that treat the highest number of persons with
      HIV infection. Patients at each site were chosen using disease stage
      (asymptomatic, symptomatic, and AIDS) and gender as the selection criteria.
      Utilization equations are estimated for AZT use, outpatient care, and
      hospitalization. DATA COLLECTION: The ACSUS involves six in-person interviews
      over an 18-month period. Interviews include questions about the use of medical
      and support services, insurance status, functional status, and barriers to care
      during the prior three-month period. PRINCIPAL FINDINGS: A male injection drug
      user (IDU) with AIDS is 20 percent more likely to be hospitalized than a woman
      with AIDS, and the hospital cost of treating a male IDU with AIDS is $9,180 more
      per year than the hospital cost of treating a woman with AIDS. CONCLUSIONS: This
      study shows that, even after being diagnosed and after having accessed the
      medical care system, women with AIDS receive fewer services than men with AIDS.

PMID- 8270421
TI  - Selection in a preferred provider organization enrollment.
AB  - OBJECTIVE: The study was conducted to determine whether favorable or adverse
      selection occurred in a preferred provider organization (PPO) enrollment. DATA
      SOURCES AND STUDY SETTING: Secondary data sources were used to conduct a
      retrospective study of the utilization of health services and the demographic
      characteristics of the population involved in the first open enrollment in a new
      university-based PPO. The PPO under study, sponsored by the University of
      Michigan (UM) Medical Center, was offered to all 43,005 UM employees, dependents,
      and retirees. STUDY DESIGN: We analyzed insurance company payments during the one
      year period prior to the enrollment to compare the utilization patterns of those
      who enrolled in the PPO with those who did not. DATA COLLECTION: Prior health
      care utilization data were obtained from Blue Cross-Blue Shield of Michigan on
      the entire university population for one year prior to the start of the PPO.
      Demographic data were obtained from the personnel office of the university.
      PRINCIPAL FINDINGS: The PPO group had a younger median age than the non-PPO
      group; the sex distribution was roughly similar for the two groups. In the PPO
      group 57 percent of all contracts were family contracts compared with only 30
      percent in the non-PPO group. The PPO group experienced 20.6 percent lower
      inpatient payments per member, and 9.4 percent lower outpatient payments per
      member in the year prior to the enrollment. These differences resulted in an
      overall 18.7 percent lower payment per member for the PPO group in the year prior
      to their enrollment. CONCLUSIONS: The results show, based on prior insurance
      payments, that this PPO received favorable selection during the open enrollment,
      a finding consistent with favorable selection found in early HMO enrollment.

PMID- 8270422
TI  - A comparison of work-sampling and time-and-motion techniques for studies in
      health services research.
AB  - OBJECTIVE: This study compares results and illustrates trade-offs between work
      sampling and time-and-motion methodologies. DATA SOURCES: Data are from time-and
      motion measurements of a sample of medical residents in two large urban
      hospitals. STUDY DESIGN: The study contrasts the precision of work-sampling and
      time-and-motion techniques using data actually collected using the time-and
      motion approach. That data set was used to generate a simulated set of work
      sampling data points. DATA COLLECTION/EXTRACTION METHODS: Trained observers
      followed residents during their 24-hour day and recorded the start and end time
      of each activity performed by the resident. The activities were coded and then
      grouped into ten major categories. Work-sampling data were derived from the raw
      time-and-motion data for hourly, half-hourly, and quarter-hourly observations.
      PRINCIPAL FINDINGS: The actual time spent on different tasks as assessed by the
      time-and-motion analysis differed from the percent of time projected by work
      sampling. The work-sampling results differed by 20 percent or more of the
      estimated value for eight of the ten activities. As expected, the standard
      deviation decreases as work-sampling observations become more frequent.
      CONCLUSIONS: Findings indicate that the work-sampling approach, as commonly
      employed, may not provide an acceptably precise approximation of the result that
      would be obtained by time-and-motion observations.

PMID- 8270424
TI  - Porter's generic strategies, discontinuous environments, and performance: a
      longitudinal study of changing strategies in the hospital industry.
AB  - OBJECTIVE: Changes in generic strategies in response to discontinuous
      environments have been relatively ignored in the management literature. This
      study reports an examination of the relationships between Porter's (1980) generic
      strategies, discontinuous environments, and performance. DATA SOURCES: Archival
      data for 1984 and 1988 were collected for 172 acute care hospitals in Florida in
      order to test these relationships. STUDY DESIGN: To examine fully the performance
      impact of changes in strategy in a discontinuous environment, a longitudinal
      research design that identified a firm's strategy at two points in time, 1984 and
      1988, was used. PRINCIPAL FINDINGS: Results indicate that firms with a proper
      strategy environment fit performed the highest, firms that did not change their
      strategy had no change in performance, and firms that changed their strategy
      toward a proper strategy environment showed an increase in performance.
      CONCLUSION: Findings support the notion that hospitals with appropriate strategy
      environment combinations will exhibit higher performance.

PMID- 8270423
TI  - Medical team interdependence as a determinant of use of clinical resources.
AB  - OBJECTIVE: Our objective, based on organization theory, is to examine whether
      interdependence among physicians leads to coordination problems that in turn may
      explain variations observed in the use of clinical resources. DATA SOURCES/STUDY
      SETTING: Secondary data about episodes of in-hospital care were collected over a
      14-month period in two midsize acute care hospitals located in two suburbs of
      Montreal, Quebec. STUDY DESIGN: Hierarchical regression analysis was used to
      assess the marginal effect of medical team interdependence on clinical resource
      utilization after taking into account the effect attributable to the nature of
      several morbidities taken as specific and distinct tasks. PRINCIPAL FINDINGS:
      Medical team interdependence is found within medical specialties as well as
      between specialties. The largest portion of resource utilization was explained by
      morbidity characteristics, whereas team interdependence had a weaker, but
      systematic effect for all morbidities studied (15 regression models out of 18
      performed). Task coordination was found to become more difficult as the number of
      physicians coming from different specialties increased in the context of
      teamwork. CONCLUSIONS: Results suggest that team practice does not entirely
      overcome coordination problems inherent to task (morbidity) interdependence. In
      considering the individual (especially the attending) physician as the main
      factor responsible for resource utilization, other factors related to team
      practice may too readily be overlooked.

PMID- 8270425
TI  - Time trends in inpatient physician spending.
AB  - OBJECTIVE: Despite falling admissions and declining lengths of stay, Medicare
      expenditures for inpatient physician services have continued to climb; this
      article seeks to understand this trend by examining the expenditures on a per
      admission basis. DATA SOURCES AND STUDY SETTING: One hundred percent Medicare
      claims data were available from nine states for the 1985-1988 time period. STUDY
      DESIGN: Because Medicare's prospective payment system encourages hospitals to
      shift some services outside the inpatient setting, we examined trends in episodes
      of care, encompassing some time both before and after the inpatient stay itself.
      Trends were also examined at the individual DRG level in order to partially
      control for case-mix shifts and increased surgical use. Allowed charges were
      purged of both Medicare fee updates and geographic price variation in order to
      derive estimates of real spending growth. DATA COLLECTION/EXTRACTION METHODS:
      Hospital and physician claims were merged to form inpatient episodes that
      included seven days prior to admission as well as 30 days following discharge.
      PRINCIPAL FINDINGS: Physician spending per episode increased 27 percent just over
      this four-year time period, but with considerable variation by DRG ranging from
      only 2 percent for transurethral prostatectomies (TURPs) to 56 percent for
      uncomplicated acute myocardial infarctions (AMIs). Changes in case severity and
      hospital and physician characteristics were all found to be important
      contributors to the increase in physician inpatient spending. Most important
      seemed to be the growth in the number of physicians associated with the inpatient
      stay (and the subsequent increase in diagnostic tests and other procedures).
      CONCLUSIONS: The findings suggest that control of technology and control of the
      number of physicians involved in the care of a patient are both critical to
      constraining the rate of increase in physician inpatient expenditures.

PMID- 8270426
TI  - Rapid detection of genetic variability in chrysanthemum (Dendranthema grandiflora
      Tzvelev) using random primers.
AB  - Genetic variation in chrysanthemum (Dendranthema grandiflora) was studied using a
      recently developed technique generating Random Amplified Polymorphic DNAs
      (RAPDs). It appeared that variation between cultivars was high and that the
      cultivars used could be distinguished from each other by using only two different
      primers. A family of cultivars, derived from one original cultivar by vegetative
      propagation, had identical fragment patterns. Because of the high level of
      polymorphism and clonal stability RAPD fragments are useful for cultivar
      identification. Genetic variability among related Dendranthema species was too
      high to study genetic distances either among cultivars within chrysanthemum or
      among species related to chrysanthemum.

PMID- 8270427
TI  - Evaluation of models of homologue search with respect to their efficiency on
      meiotic pairing.
AB  - We have constructed models of how homologous chromosomes come together at meiotic
      prophase for pairing and recombination. For these models we have calculated how
      many homology testing events are necessary on average to ensure that each
      chromosome finds its respective partner. We have identified several conditions
      that would greatly reduce the effort spent on homology search when compare with a
      search strategy which is based on fortuitous homologous contracts. The models are
      discussed in the light of experimental evidence.

PMID- 8270428
TI  - Constraints on the evolution of attractive traits: genetic (co)variance of zebra
      finch bill colour.
AB  - We estimated the heritability and genetic correlation between male and female
      bill colour in a laboratory population of zebra finches (Taeniopygia guttata) in
      order to examine the potential genetic constraints on the evolution of a sexually
      dimorphic trait. The heritability estimates of bill colour from regressions of
      offspring on single parents ranged from h2 = 0.34 to 0.73 and all but one of
      these estimates were significantly greater than zero. The restricted maximum
      likelihood heritability estimates for full- and half-siblings were significant
      for females (h2 = 0.48) but not significant for males (h2 = 0.45). The maximum
      likelihood estimates indicate that there is little dominance genetic variance for
      bill colour. The large genetic correlation between male and female bill colour
      (rg = 0.91) combined with opposing selection on male and female bill colour
      indicates that the evolution to sex-specific optima may proceed very slowly.

PMID- 8270429
TI  - Management of pterygium with surgery and radiation therapy. The North Florida
      Pterygium Study Group.
AB  - PURPOSE: To compare our results in the management of pterygium using a higher
      total dose with other reported results. METHODS AND MATERIALS: Between 1971 and
      1991, 690 patients were treated with complete surgical excision followed by beta
      irradiation for primary or recurrent pterygium. Of these patients, 129 had two or
      more areas involving both eyes for a total of 825 lesions treated. Only 17
      patients (2%) had temporal lesions with the rest of the patients having nasal
      pterygia. All patients underwent complete surgical resection of the pterygium
      before undergoing radiation therapy. One hundred forty-nine patients had
      undergone previous surgical resection alone but developed recurrence. After
      surgical excision, all patients were treated with Strontium-90 applicators
      starting immediately within 24 hr of surgery. Our standard policy was six weekly
      applications, each delivering a surface dose of 1000 cGy. The total dose
      delivered was 6000 cGy. Minimum follow-up was 1 year with a median of greater
      than 8 years. RESULTS: There were only fourteen recurrences (1.7%) out of a total
      of 825 lesions treated. Nine of the fourteen patients received suboptimal therapy
      undergoing less than five applications of Strontium-90. There were no major
      complications. CONCLUSION: The combination of surgical excision followed by
      adequate Strontium-90 applications is highly effective in the management of
      pterygium. The optimal total dose appears to be in the range of 2000 cGy to 6000
      cGy.

PMID- 8270430
TI  - Ductal carcinoma in situ of the breast: results of treatment by conservative
      surgery and definitive irradiation.
AB  - PURPOSE: To determine local control, survivorship, and cosmesis in women with
      ductal carcinoma in situ treated by conservative surgery and radiation therapy.
      METHODS AND MATERIALS: We retrospectively analyzed the results of treatment in 56
      women with in situ carcinoma of the breast, treated between 1976 and 1990 by
      conservative surgery and irradiation. Two women had bilateral tumors, for a total
      of 58 breasts at risk. All patients underwent gross excision of the tumor
      followed by radiation to the entire breast and a sequential boost to the tumor
      bed. Eight of the 21 evaluable tumors (38%) had inadequate pathologic margins at
      the time of excision. Routine re-excision was not performed. The median dose to
      the whole breast and primary tumor site was 5000 cGy and 6940 cGy, respectively.
      Median follow-up was 61 months (range 27-191 months). RESULTS: Five patients (9%)
      failed in the breast for an 8-year actuarial local failure rate of 11%. Median
      time to failure was 34 months. All five patients with local recurrence underwent
      mastectomy and are alive, without evidence of disease at a mean of 40 months post
      mastectomy. The 8-year actuarial absolute and cause specific survivals were 89%
      and 100%, respectively. Cosmetic results were excellent or totally acceptable in
      90% of patients. CONCLUSION: Patients with ductal carcinoma in situ treated by
      excision and irradiation achieved acceptable local control and excellent survival
      and cosmetic results. Because of the long time course associated with local
      failure, diligent and protracted follow-up is mandatory.

PMID- 8270431
TI  - The relationship between brachytherapy dose and outcome in patients with bulky
      endocervical tumors treated with radiation alone.
AB  - PURPOSE: To evaluate the relationship between brachytherapy dose and outcome in
      patients treated with external radiotherapy (40 Gy to the whole pelvis) and
      intracavitary radium therapy for bulky endocervical tumors. METHODS AND
      MATERIALS: Between 1962 and 1985, 98 patients with Stage IB-IIB bulky
      endocervical carcinomas (> or = 6 cm in diameter) treated with radiotherapy alone
      received 40 Gy to the whole pelvis followed by 2 or more intracavitary
      treatments. Twenty-five patients received < 6000 mg-hr of intracavitary treatment
      and 73 received > or = 6000 mg-hr (an average dose to point A of approximately 49
      Gy). Brachytherapy exposures ranged from 4800-7885 mg-hrs. RESULTS: Patients who
      received < 6000 mg-hr tended to have unfavorable (narrow) vaginal anatomy (p <
      0.01) and to be treated in the later years of the study (p < 0.01). The high-dose
      group included a somewhat greater proportion of patients with positive
      lymphangiograms or poor responses to initial external beam treatment. Despite
      having somewhat more favorable tumors, patients who received less than 6000 mg-hr
      had a higher rate of pelvic disease recurrence at 5 years (33%) than those who
      received higher doses (16%) (p = 0.03). Actuarial survival rates at 5 years were
      44% and 60% for the low- and high-dose groups, respectively (p = 0.14). Among
      those who received more than 6000 mg-hr, there was no significant relationship
      between brachytherapy dose and pelvic disease control. Calculated actuarially,
      the rate of major (> or = grade 3) complications at 5 years was 23% in the low
      dose group and 10% in the high-dose group (p = 0.1). CONCLUSIONS: The relatively
      high incidence of pelvic disease recurrence and complications in patients who
      receive less than 6000 mg-hr reflects the narrow therapeutic window for
      complication-free pelvic disease control in patients with bulky central disease
      and unfavorable normal tissue anatomy. The results also demonstrate a high pelvic
      control rate and acceptable morbidity in patients with favorable anatomy treated
      with high-dose radiotherapy alone.

PMID- 8270432
TI  - The hypoxic cytotoxin SR 4233 increases the effectiveness of radioimmunotherapy
      in mice with human non-Hodgkin's lymphoma xenografts.
AB  - PURPOSE: To determine if either the hypoxic cell radiosensitizer etanidazole (SR
      2508) or the hypoxic cytotoxin SR 4233 could improve the effectiveness of
      radioimmunotherapy. METHODS AND MATERIALS: LC4 (an IgG1 monoclonal antibody
      directed toward malignant T cells) and MB-1 (an irrelevant isotype-matched
      control antibody) were injected intraperitoneally into severe combined
      immunodeficient phenotype mice with human cutaneous T cell lymphoma xenografts in
      order to determine the distribution of the antibodies in the tumors and normal
      tissues as a function of time. Computerized-pO2-histography was used to measure
      the median oxygen tension in the tumors. Tumor-bearing mice were treated with:
      (a) LC4; (b) 90Y-LC4; (c) 90Y-MB-1; (d) whole body irradiation delivered via an
      external 137Cs source; (e) etanidazole and 90Y-LC4; (f) SR 4233 and 90Y-LC4; (g)
      etanidazole; and (h) SR 4233. An additional group of mice received no treatment
      and served as controls. A tumor growth delay assay was used to assess the
      effectiveness of the different treatment regimens. RESULTS: LC4 accumulated in
      the tumors to a significantly greater extent than MB-1 (p < 0.001) and reached a
      peak concentration in the tumors 5 days post-injection. The human cutaneous T
      cell lymphoma xenografts had a relatively low median oxygen tension. LC4 by
      itself was able to produce a minor decrease in tumor size (control vs. LC4; p =
      0.001). 90Y-LC4 produced greater tumor growth delay than LC4 alone (LC4 vs. 90Y
      LC4; p = 0.01); however, the Yttrium-90 caused neutropenia and weight loss. The
      90Y-labeled tumor-specific and non-specific antibodies both exerted greater tumor
      growth delay than externally delivered whole body irradiation (p < or = 0.03) due
      to preferential uptake of the antibodies in the tumors. Etanidazole and SR 4233
      by themselves did not significantly inhibit the growth of the tumors. Etanidazole
      did not significantly enhance the tumor growth delay produced by 90Y-LC4 (90Y-LC4
      vs etanidazole and 90Y-LC4, p = 0.13). SR 4233, on the other hand, did enhance
      the tumor growth delay produced by 90Y-LC4 (90Y-LC4 vs. SR 4233 and 90Y-LC4, p =
      0.046). The neutropenia and weight loss caused by 90Y-LC4 were exacerbated
      slightly (< 10%) by the administration of SR 4233. CONCLUSIONS: A first
      generation hypoxic cytotoxin, SR 4233, was able to enhance the tumor growth delay
      produced by radioimmunotherapy in severe combined immunodeficient phenotype mice
      with human cutaneous T cell lymphoma xenografts.

PMID- 8270433
TI  - Combination therapy with radiation, mitomycin C, and 5-fluorouracil in EMT6
      tumors.
AB  - PURPOSE: The primary purpose of these studies was to assess whether concomitant
      treatment with 5-fluorouracil increased the cytotoxicity of radiation, mitomycin
      C, or the combination of these two agents to cells in solid tumors. METHODS AND
      MATERIALS: All studies were performed using EMT6 mouse mammary tumor cells. In
      vitro studies used exponentially-growing monolayers. In vivo studies used solid
      EMT6 tumors growing in BALB/c Rw mice. The effects of treatment on tumors or
      cultures were assessed using clonogenic assays which considered both the colony
      forming abilities of the intact cells and the numbers of cells in the cultures or
      tumors. RESULTS: EMT6 cells in vitro were killed effectively by 5-fluorouracil.
      The cytotoxicity increased as the drug concentration increased from 1 microM to 1
      mM or as the treatment time increased from 1 to 48 hr. However, 5-fluorouracil
      was only marginally active against solid EMT6 tumors: treatment with doses of up
      to 400 micrograms/gm killed less than 50% of the tumor cells, regardless of
      whether the drug was given as an injection or an infusion over 48 hr and
      regardless of the time between injection of the drug and assay of cell survival.
      Treatment with 5-fluorouracil produced only a statistically insignificant
      increase in the effect of 15 Gy of x-rays, whether the drug was given by
      injection or infusion over 48 hr. Both injection of 200 micrograms/g 5 FU and
      infusion of 100 micrograms/g 5-fluorouracil decreased the cytotoxicity of 6
      micrograms/g of MC to cells in solid tumors. Injection of 200 micrograms/g of 5
      fluorouracil decreased the cytotoxic effects of a regimen combining 6
      micrograms/g MC plus 15 Gy of x-rays. CONCLUSION: In this solid tumor system, a
      regimen combining single doses of mitomycin C and x-rays was more effective in
      killing the tumor cells than was the same regimen combined with 5-fluorouracil.

PMID- 8270434
TI  - The effects of radiation on the expression of a newly cloned and characterized
      rat cyclin B mRNA.
AB  - PURPOSE: To evaluate the hypothesis that the radiation induced G2 delay in the
      cell cycle is associated with radiation induced effects on cyclin B expression in
      a rodent cell system. METHODS AND MATERIALS: Two rodent, rat and Chinese hamster,
      cyclin B cDNAs were cloned and characterized. The two rodent species were 85% and
      86% identical, respectively, when compared to the human cyclin B, indicating that
      they are the rodent homologous of cyclin B. 3.7 cells (rat embryo cells
      transformed by H-ras and v-myc) were synchronized and then irradiated. Flow
      cytometry and Northern blots were performed to evaluate the effects of radiation
      on cyclin expression in relation to phase of the cell cycle. RESULTS: Examination
      of the rodent cyclin B sequences revealed only two regions with significant
      divergence to the human sequence, one in the lysine rich region adjacent to the
      cyclin destruction box, which is the putative site for ubiquitination, and one at
      the C terminal end. Although many of the amino acids diverged in the lysine rich
      region, the positions of the lysines themselves were virtually invariant
      suggesting their potential importance in ubiquitination. Both rodent species were
      also noted to have a PEST-like sequence which occurs in the human, but not in non
      mammalian cyclins cloned to date and could also potentially contribute to rapid
      destruction. The rat and Chinese hamster mRNAs contain much longer 3'
      untranslated regions than the published human sequence with multiple AUUUA and
      AUUU motifs which are seen in other mRNAs with rapid turnover times. This feature
      has not been previously found in cyclin mRNAs. In addition we have found that in
      the 3' region of the rodent cDNAs we find two potential polyadenylation sites
      suggesting that this gene may have several transcripts. Our studies suggest that
      multiple mechanisms of control of mammalian cyclin B destruction exist, both at
      the mRNA and protein level. Evidence is also provided that the levels of rat
      cyclin B mRNA peaks during G2/M. Irradiation is shown to induce a G2 delay in
      synchronized 3.7 cells, compared to unirradiated controls, and the delay is
      temporally related to decreased levels of cyclin B mRNA expression. Since the G2
      delay induced by ionizing radiation may contribute to the ability of cells to
      survive irradiation, cyclin B expression may be a key component in the
      determination of sensitivity or resistance to radiation therapy. CONCLUSION: The
      isolation and characterization of two rodent cyclin B's confirm that multiple
      mechanisms of control of mammalian cyclin B destruction exist. Our studies show
      that rat cyclin B expression is influenced by radiation and is temporally related
      to the delay in the G2 phase induced by radiation.

PMID- 8270435
TI  - Comparison of the enhancement of tumor responses to fractionated irradiation by
      SR 4233 (tirapazamine) and by nicotinamide with carbogen.
AB  - PURPOSE: This study was undertaken to compare in a fractionated regimen, with
      clinically relevant radiation doses, two radiation response modifiers that
      function by different mechanisms: SR 4233, a bioreductive agent toxic to hypoxic
      cells, and nicotinamide with carbogen, a combination that has been shown to
      improve tumor oxygenation. METHODS AND MATERIALS: Cell survival assays were used
      to examine the response of three different tumors: KHT, RIF-1 and SCCVII/St in
      C3H/Km mice. Regrowth delay studies were also performed with the RIF-1 tumor. A
      fractionated irradiation schedule, consisting of twice daily 2.5 Gy treatments
      was investigated with and without drug pretreatment. SR 4233 was given IP at 0.12
      mmol/kg one half hour before each irradiation. Nicotinamide (250, 500, 1000
      mg/kg) was given IP 1 h before each irradiation with carbogen exposure 5 min
      prior to and during the irradiation. RESULTS: Both treatment strategies enhanced
      the response of all three tumors to the fractionated radiation regimen. However,
      for two of the tumors (KHT and SCCVII), SR 4233 produced a significantly greater
      enhancement than did the combination of nicotinamide + carbogen. For the RIF-1
      tumor (which has the lowest hypoxic fraction of the three), the response was
      comparable for the two modalities. For nicotinamide + carbogen, there was no
      significant change in the radiation enhancement at nicotinamide doses between 250
      and 1000 mg/kg. CONCLUSION: Adding the bioreductive cytotoxin SR 4233 or
      nicotinamide + carbogen to fractionated irradiation enhances the response of the
      three transplanted tumors used in this study to fractionated irradiation. The
      radiation enhancement was significantly greater, however, for SR 4233 for two of
      the tumors with comparable results in the third. The data are consistent with the
      prediction that killing tumor hypoxic cells can produce a similar or greater
      enhancement of the efficacy of fractionated radiation in enhancing tumor response
      than either oxygenating or radiosensitizing these cells.

PMID- 8270436
TI  - Thermometry of interstitial hyperthermia given as an adjuvant to brachytherapy
      for the treatment of carcinoma of the prostate.
AB  - PURPOSE: Recurrence in the prostatic gland remains a significant problem in the
      management of locally advanced prostatic cancer. Transperineal
      thermobrachytherapy has been utilized in an attempt to improve local tumor
      control. The purpose of this study was to quantitate the temperature
      distributions obtained in carcinoma of the prostate treated with interstitial
      radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy
      in a Phase I study. METHODS AND MATERIALS: From 1987 until 1992, 36 patients (5
      with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were
      treated with interstitial brachytherapy implants supplemented with radiofrequency
      induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer
      diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the
      prostate gland through a perineal approach utilizing a specially designed
      template. Each trocar was electrically insulated along the length which traversed
      surrounding normal tissues. One to three additional plastic catheters were
      implanted for automated temperature mapping. Thirty-four of these procedures were
      performed following lymph node sampling. However, the last two removable
      interstitial hyperthermic prostate implants were done by the transperineal route
      under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45
      minutes) was given immediately prior to the insertion and immediately following
      the removal of the 192Ir. A computer-controlled radiofrequency-based generator
      (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and
      maintain elevated temperatures. RESULTS: Transient local pain was the most common
      treatment limiting factor. The average values of the measured minimum, mean, and
      maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in
      tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding
      normal tissue, respectively. The percentages of mapped temperatures exceeding 41
      degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and
      26%, 11%, and 4% in normal surrounding tissue, respectively. CONCLUSION: From
      this study we conclude that heterogeneous temperature distributions were induced
      in the prostate; significant normal tissue protection was realized in part
      through the selective insulation of sections of each electrode; and interstitial
      radiofrequency-induced hyperthermia of the prostate is feasible and well
      tolerated, with further technical developments warranted.

PMID- 8270437
TI  - Report of long-term follow-up in a randomized trial comparing radiation therapy
      and radiation therapy plus hyperthermia to metastatic lymph nodes in stage IV
      head and neck patients.
AB  - PURPOSE: The treatment of inoperable metastatic lymph nodes in patients with head
      and neck cancer represents a therapeutic challenge. Clinical results using
      conventional radiation therapy are disappointing; on the other hand, the
      evaluation of recent innovative radiotherapeutic methods is still pending. The
      end points of this analysis were focused on long-term local control, on its
      potential influence on survival, and on late toxicity of a previously reported
      randomized Phase III study comparing conventionally fractionated radical
      irradiation alone or combined with local hyperthermia in fixed and inoperable
      metastatic neck lymph nodes. METHODS AND MATERIALS: The medical records of 41
      patients (44 nodes) with advanced locoregional Stage IV squamous cell cancer of
      the head and neck and randomized to treatment in the period 1985-1986 with
      irradiation alone (22/23 evaluable nodes) or combined with external hyperthermia
      (18/21 evaluable nodes), were re-evaluated. RESULTS: The statistically
      significant difference observed in "early" response (p = 0.0164) in favor of the
      combined treatment results in improved 5-year actuarial nodal control (p =
      0.015). Clinical improvement noted in tumor control positively affects survival,
      leading to a statistically significant difference in survival at 5 years (p =
      0.02). With respect to side effects, no clearly enhanced acute or late toxicity
      has been found; as severe late effects, two patients with bone necroses possibly
      related to the combined treatment have been observed. Thermal analysis failed to
      show a significant correlation between heating parameters and the end points of
      the study. CONCLUSION: This report with 5-year follow-up confirms the efficacy
      and the absence of severe toxicity of the combination of radical radiation and
      hyperthermia in the treatment of metastatic lymph nodes in Stage IV squamous cell
      carcinoma of the head and neck.

PMID- 8270438
TI  - Predictors of survival after a positive post-irradiation prostate biopsy.
AB  - PURPOSE: Considerable debate persists in the urologic oncology literature with
      regard to the optimum management of patients with a positive post-irradiation
      prostate biopsy. This analysis characterizes a group of such patients who have
      had a favorable course without intervention. METHODS AND MATERIALS: Between 1956
      and 1991, 116 patients have had a positive prostate biopsy 12 or more months post
      irradiation without hormonal intervention or evidence of distant relapse. The
      population had an age range of 42 to 82 years (median - 61). American Joint
      Committee on Cancer stages included 1 T1, 70 T2, 44 T3, and 1 T4. Median
      actuarial survival for the entire population was 14.4 years (range = 2.2-21.5
      years) from presentation and 5.2 years from re-biopsy. RESULTS: Fifty-one of the
      116 patients developed metastases subsequent to re-biopsy and 65 remain free from
      distant relapse. Among these 65 patients, 50 remain alive and otherwise well, 11
      have died of other causes, and only four have succumbed to their local disease.
      The best predictor of distant relapse subsequent to re-biopsy was digital rectal
      exam. Forty-one of the 51 patients later developing metastases had an abnormal
      digital rectal exam compared to 37 of 65 with sustained distant control (p =
      .01). CONCLUSION: These data demonstrate that long-term, disease-free (other than
      re-biopsy) survival is common following a "positive" post-irradiation biopsy
      without intervention especially among patients with a normal digital rectal exam.
      Therefore, routine re-biopsy without clinical indications is not a useful
      practice.

PMID- 8270439
TI  - Hyperthermic enhancement of high dose-rate irradiation in 9L gliosarcoma cells.
AB  - PURPOSE: Long duration-mild temperature hyperthermia has previously been shown to
      be an effective potentiator of low-dose-rate irradiation. An in vitro
      investigation was initiated to determine if 41 degrees C hyperthermia could be
      useful in sensitizing high-dose-rate (HDR) brachytherapy. Experiments were
      designed to determine the optimal length of heat treatments to be applied with a
      twice daily 5 Gy times five fraction high-dose-rate protocol. METHODS AND
      MATERIALS: Rat 9L gliosarcoma cells growing exponentially in flasks were exposed
      to X-irradiation and 41 degrees C hyperthermia. Irradiation was applied in 5 Gy
      fractions two times per day to a total dose of 25 Gy. Hyperthermia consisted of
      combinations of 1 or 4 hr heating before and/or after each of the radiation
      exposures. In addition, a set of cells was heated continuously at 41 degrees C
      starting 6 hr before the first fraction and continuing to 4 hr after the 5th
      fraction. Cell survival was assayed by colony formation. RESULTS: Sensitization
      of high-dose-rate increased linearly with increasing length of 41 degrees C
      heating over the entire range of heat exposures applied. Maximum sensitization
      was produced by continuous heating for 58 hr throughout the entire radiation
      course. Heating for 4 hr before fractions two through five produced less
      sensitization to these later fractions than was expected if each heat-radiation
      fraction had acted independent of the other fractions. CONCLUSION: Continuous 41
      degrees C heating eliminated split dose sparing during high-dose-rate. The
      apparent development of thermotolerance during the course of heat and high-dose
      rate resulted in reduced sensitization in the later fractions when 4 hr pre-
      and/or post-heat were applied. This tolerance was overcome if heat was applied
      continuously between radiation fractions. The clinical relevance of these in
      vitro data is that 41 degrees C hyperthermia should be applied for as long as is
      possible during this type of high-dose-rate protocol. This combined hyperthermia
      high-dose-rate treatment may enhance the efficacy of interstitial irradiation in
      situations such as boost irradiation of high grade glioma.

PMID- 8270440
TI  - Altered regulation of heat shock gene expression in heat resistant mouse cells.
AB  - PURPOSE: The differences in the heat shock gene regulation between the RIF-1 cell
      line and its heat resistant derivative TR4 are further characterized. METHODS AND
      MATERIALS: In vitro gel retardation assays were used to assess the presence of
      activated heat shock transcription factor in the two cell lines. The levels of
      the heat-inducible HSP 70.1, the constitutive HSC 70, the germ line-specific HSP
      70.2, and the HSP 28 mRNAs in both untreated and iso-heated RIF-1 and TR4 cells
      were determined using the polymerase chain reaction coupled with the reverse
      transcriptase reaction. Induction and decay of induced heat shock protein
      synthesis was measured by 35S-methionine labeling of proteins. RESULTS: Unheated
      TR4 cells display characteristics of heat shocked RIF-1 cells. TR4 cells have a
      constitutively activated heat shock transcription factor and elevated levels of
      the HSP 70.1, HSC 70, and the HSP 28 mRNAs. Upon an equal heat dose of 45 degrees
      C, 15 min, the TR4 cells exhibited a more rapid onset in heat shock mRNA and
      protein induction than did the RIF-1 cells. During the recovery from heat shock,
      the activated heat shock transcription factor and the induced HSP70 mRNAs decayed
      more slowly in the TR4 cells, although the protein synthesis pattern of the TR4
      cells returned to control levels more rapidly following heat shock than did
      protein synthesis of the RIF-1 cells. CONCLUSION: Unheated TR4 cells are similar
      to heat shocked RIF-1 cells at the transcriptional level. Induced HSP70
      expression is modulated by the severity of the heat treatment (or the degree of
      heat damage) perceived by the cells rather than by the absolute heat dose given.
      We propose that the unheated TR4 cells are locked into the "ON" state of the heat
      shock response.

PMID- 8270441
TI  - Interstitial hyperthermia and high dose rate brachytherapy in the treatment of
      anal cancer: a phase I/II study.
AB  - PURPOSE: The rate of local failure is sufficiently high following sphincter
      conserving surgery and radiation therapy for advanced anal cancers to warrant
      investigation of improved local treatment techniques. This Phase I/II study was
      undertaken to investigate the site-specific toxicities and response of Stage II
      and III anal cancers to interstitial thermoradiotherapy using a hot water
      interstitial system. METHODS AND MATERIALS: Between September 1988 and March
      1991, 14 patients with primary carcinomas of the anal canal, UICC Stage T2-3, N0
      1, M0, were treated with split-course external beam irradiation to the pelvis (30
      Gy + 20 Gy) and 1 or 2 interstitial Iridium-192 high dose rate (Ir-192 HDR)
      implants (6-8 Gy each) immediately followed by interstitial hyperthermia (HT).
      Patients with tumor diameters > 3 cm were scheduled to receive chemotherapy
      consisting of 2 courses of 5-fluorouracil and mitomycin C given concomitantly
      with external beam radiation. Interstitial hyperthermia was induced by
      circulating warm water through the needles that were implanted to hold the Ir-192
      source. The treatment goal was to achieve and maintain a temperature of 42.5
      degrees C over a time period of 40 min. A 3-point thermocouple probe inserted
      into one or two additional needles was used for thermometry. The temperatures
      were recorded by manual mapping along these needles at steps of 0.5 or 1 cm.
      RESULTS: A total of 20 Ir-192 HDR-HT implants were performed in 14 patients. All
      but two patients completed the external beam irradiation; five patients received
      concomitant chemotherapy. Analysis of thermal parameters showed that minimum
      intratumoral temperatures (Tmin) of 42 degrees C, 42.5 degrees C, 43 degrees C,
      and 44 degrees C were achieved in 64%, 37.5%, 14%, and 7% of patients,
      respectively. Intratumoral mean Tmin, mean average, and mean maximum temperatures
      for these patients were 41.7 degrees C, 42.4 degrees C, and 43.4 degrees C,
      respectively. Brachytherapy and HT were well tolerated. Clinical complete
      responses (cCR) were obtained in 11/14 (78.5%) patients, complete
      histopathological responses (pCR) in 10/14 (71%). Only one patient with pCR
      recurred and succumbed to her disease. Patients with persistent disease (1
      minimal and 3 partial responders, including 1 cCR) underwent abdominal-perineal
      resection but subsequently died from local-regional recurrence. One patient with
      pCR died from unrelated causes. Median survival for all patients from onset of
      radiation to death or last follow-up is 26 months. Eight patients are alive
      disease-free after a follow-up ranging from 16-44 months (median: 30, mean: 30
      months). Treatment complications were limited to two patients who developed
      persistent ulcers. Sphincter function was maintained in 50% of patients.
      CONCLUSION: This study demonstrates that interstitial warm water hyperthermia in
      combination with brachytherapy for anal carcinomas is feasible and did not add to
      complications when compared to studies employing external beam irradiation and
      brachytherapy alone. The thermal parameters obtained by the warm water system
      compare favorably to those reported by others using radiofrequency and microwave
      systems.

PMID- 8270442
TI  - RTOG #89-06: a phase I study to evaluate intraoperative radiation therapy and the
      hypoxic cell sensitizer etanidazole in locally advanced malignancies.
AB  - PURPOSE: To identify the maximum tolerated dose of the oxygen mimetic radiation
      sensitizer Etanidazole in the setting of surgery and intraoperative radiation
      therapy. 12 grams/meter2 was the maximum chosen target dose based on tolerance
      from other trials. METHODS AND MATERIALS: 42 patients were entered in an
      escalating dose scheme, 5.5, 7.5, 9, 10.5, and 12.0 grams/meter2. Etanidazole was
      given via intravenous infusion over 15 minutes, followed within 20 to 30 minutes
      by intraoperative radiation therapy. Multiple tissue samples from tumor, tumor
      bed, and/or normal tissue were obtained with simultaneous plasma samples.
      Etanidazole concentrations in tissue and serum were determined in 33 of the 42
      patients. RESULTS: The median time to maximum serum concentration was 25 minutes.
      Median time to maximum tissue concentration was 40 minutes. Tissue concentrations
      began falling approximately one hour after infusion. Acute drug toxicities were
      minimal. Toxicities reported during follow-up related to surgery and/or
      radiation, not to drug. The concentration of sensitizer in tumor/tumor bed
      tissues was ten-fold greater than in previous trials. A sensitizer enhancement
      ratio for the hypoxic cells of 2 to 2.5 is projected. CONCLUSION: On the basis of
      tissue biopsy information, intraoperative radiation therapy will be given 40
      minutes after the start of the 15 minute infusion allowing time for maximum
      intracellular uptake into tumor cells. In view of these findings, a Phase III
      trial testing etanidazole with intraoperative radiation therapy will be
      conducted. The tolerable single dose level of 12 grams/meter2 has potential with
      other high-dose radiation settings such as brachytherapy or stereotactic
      radiosurgery.

PMID- 8270443
TI  - Evaluation of external-beam radiation therapy plus 5-fluorouracil (5-FU) versus
      external-beam radiation therapy plus hycanthone (HYC) in confined, unresectable
      pancreatic cancer.
AB  - From March 1981 to November 1987, 87 patients with histologically confirmed
      pancreatic adenocarcinoma, unresectable but confined to the pancreatic region,
      were randomized to two treatments. The standard treatment was 40-50 Gy external
      beam radiation therapy (RT) to gross tumor plus potential microscopic tumor with
      a 5 Gy boost to gross tumor plus a 1.5-2.0 cm margin, using multiple fields and 5
      fluorouracil (5-FU) 500 mg/m2/d intravenously by rapid infusion. The 5-FU was
      given each of the initial 3 days of each of three 20 Gy radiation courses. The
      experimental treatment used identical radiation fields, but the two Gy daily
      radiation fractions were administered in a continuous course to a total dose of
      50 Gy. Hycanthone was administered 60 mg/m2 intravenously within 2 to 4 hr during
      each day of the 5-day course of infusions during the first and fifth weeks of
      radiation therapy. There was no statistically significant difference between
      treatment arms in survival (p = 0.82) or disease-free survival (p = 0.27). Seven
      percent of hycanthone-treated patients demonstrated hepatic toxicity which was
      usually mild in nature. There was, however, one death due to hepatic toxicity.

PMID- 8270444
TI  - A phase I/II trial of twice daily irradiation and concurrent chemotherapy for
      locally advanced squamous cell carcinoma of the head and neck.
AB  - PURPOSE: This study was designed to test the toxicity and efficacy of a regimen
      of twice daily irradiation and concurrent multiagent chemotherapy for patients
      with locally advanced squamous cell carcinoma of the head and neck. METHODS AND
      MATERIALS: This was a prospective Phase I/II trial. Patients received 125 cGy
      b.i.d. to 7000 cGy with a 6 hr interfraction interval. Chemotherapy was given
      during weeks 1 and 6 of irradiation and consisted of a 5 day infusion of 5
      fluorouracil at 600 mg/M2/day and 5 daily injections of cisplatin at 12
      mg/M2/day. Two additional cycles of chemotherapy were given after the completion
      of radiotherapy. RESULTS: Forty-six patients were evaluable: 28 had technically
      unresectable disease and 18 had resectable tumors. All had Stage III or IV
      disease: 84% had T3 or T4 primaries while 53% had > or = N2 neck disease. The
      primary acute toxicity, confluent mucositis, was seen in 74% of patients. Late
      side effects occurred in four patients. Median follow-up is 36 months (range 25
      44 months). Kaplan-Meier estimates of 2-year disease-free survival and overall
      survival are 65% and 73%, respectively, while 2-year local regional control and
      distant disease-free survival are 72% and 88%, respectively. Multivariate
      analysis revealed that resectability and receiving > 2 cycles of chemotherapy
      significantly influenced local regional control while age < 60 significantly
      influenced disease-free survival. CONCLUSION: This form of treatment can be
      delivered safely. The encouraging results have led to the initiation of a Phase
      III trial comparing this regimen with b.i.d. radiation alone.

PMID- 8270445
TI  - Iridium-192 interstitial implant and external beam radiation therapy in the
      management of squamous cell carcinomas of the tonsil and soft palate.
AB  - PURPOSE: To evaluate the results, techniques, indications and complications of
      interstitial brachytherapy in the management of squamous cell carcinomas of the
      tonsil and soft palate, we reviewed the Stanford University Medical School
      experience with this modality. METHODS AND MATERIALS: Between May 1975 and
      January 1990, 37 patients with squamous cell carcinomas of the Tonsillo-Palatine
      region were treated with a combination of external beam irradiation and a
      removable Iridium-192 interstitial implant. The mean age of these patients was
      56. Twenty-two were males and 15 were females. The stage distribution included
      four patients with Stage I, 5 with Stage II, 10 with Stage III, and 18 with Stage
      IV cancers. Thirty-two percent (12/37) of these patients had T3 or T4 lesions.
      Forty-nine percent (18/37) had stage N2 or N3 cervical lymphadenopathy. All 37
      patients received initial external beam irradiation to the primary, bilateral
      necks, and supraclavicular region (mean dose: 5400 cGy, range 4000-6600).
      Eighteen patients (49%) also received neck dissections. All 37 patients received
      an interstitial Irridium-192 implant using a combination intraoral swage and
      external looping technique. The mean dose was 2700 cGy (range 2000-4000 cGy) to
      an average volume of 24 cc (range 5-81). RESULTS: Local control was obtained in
      95% (35/37) of the patients. Eighty-seven percent (32/37) of the patients have
      remained disease-free in the neck. Nine patients have developed second primary
      lesions, and one developed pulmonary metastasis. Fifteen patients have died (6
      succumbed to their cancers, 6 to second primaries, 2 to intercurrent disease, 1
      from an unknown cause). The actuarial freedom from relapse is 75%, and overall
      survival is 64% at 5 years, with a mean follow up of 43 months (range 5-110).
      Complications were limited to one case of osteoradionecrosis of the mandible and
      one tonsillar ulcer. Functional and esthetic integrity was preserved in most of
      these patients. CONCLUSION: Iridium-192 interstitial implant boost combined with
      external beam radiation therapy is a safe and effective therapy in the management
      of locally advanced carcinomas of the tonsil and soft palate.

PMID- 8270446
TI  - Radiation therapy of pineal region tumors: 25 new cases and a review of 208
      previously reported cases.
AB  - PURPOSE: Malignant pineal region tumors are rare neoplasms arising in midline
      structures of the brain. This report analyzes the influence of histology, tumor
      location, radiation dose, treatment volume, age and cerebrospinal fluid findings
      on freedom from relapse, freedom from spinal relapse and survival. METHODS AND
      MATERIALS: Patient and treatment parameters of 25 cases of pineal region tumors
      managed at Stanford University are presented, and an additional 208 published
      cases were reviewed. Univariate and multivariate analysis were performed to
      delineate parameters predictive of freedom from relapse, freedom from spinal
      relapse, and survival for all 233 patients. RESULTS: The 5- and 10-year freedom
      from relapse for Stanford patients was 63% and 46%, respectively. The 5- and 10
      year survival for Stanford patients was 67% and 61%, respectively. The 5- and 10
      year freedom from relapse for the total 233 cases was 66% and 61%, respectively.
      The 5- and 10-year survival for all patients was 74% and 68%, respectively. For
      the entire group, biopsy confirmed germinoma and non-biopsied tumors had superior
      freedom from relapse compared to non-germinoma germ cell tumors (p = 0.03, p =
      0.005, respectively). Non-biopsied patients had improved survival compared to non
      germinoma germ cell tumors (p = 0.004). Pineal parenchymal tumors had worse
      freedom from relapse compared to non-biopsied patients (p = 0.04). For patients
      with suprasellar tumors, germinomas were associated with improved freedom from
      relapse compared to non-germinoma germ cell tumors (p = 0.02). Simultaneous
      pineal and suprasellar tumors had superior survival compared to solitary tumors
      of pineal (p = 0.04), suprasellar (p = 0.03), or third ventricle location (p =
      0.03). Twenty-two patients (9.4%) developed isolated spinal relapse. Five- and 10
      year spinal relapse rates for all patients were 11% and 13%. Survival after
      spinal relapse was 19%. Pineal parenchymal tumors had lower freedom from spinal
      relapse compared to non-biopsied patients (p = 0.001). For tumors located in the
      pineal gland, germinomas and pineal parenchymal tumors had lower freedom from
      spinal relapse than did non-biopsied patients (p = 0.006, p = 0.004,
      respectively). Pineal germinomas had lower freedom from spinal relapse than
      germinomas with suprasellar location (p = 0.04). Univariate and multivariate
      analysis identified tumor histology as the most significant predictor of freedom
      from relapse, freedom from spinal relapse and survival. CONCLUSION: Histologic
      type had the greatest impact on outcome. Treatment recommendations should be
      based on assessment of histologic type and extent of disease.

PMID- 8270447
TI  - Fractionated high-dose rate brachytherapy for intracranial gliomas.
AB  - PURPOSE: To develop a catheter system for fractionated high-dose rate (HDR)
      brachytherapy for intracranial gliomas. METHODS AND MATERIALS: The catheter
      system for stereotactic placement as well as delivery of the high-dose rate
      iridium-192 source wire is described. The force of the impulse wave from the
      source wire entering brain equivalent material was measured. Dose volume
      histograms for the first 5 patients treated are presented. RESULTS: The catheter
      system was found to be satisfactory. The maximum force of the impulse wave was
      less than 1 acceleration of gravity (which is safe). The patients tolerated the
      treatment well with no significant problems related to the catheters being left
      in situ for up to 14 days. CONCLUSION: Based on this pilot experience a phase I
      dose escalating and morbidity study has been initiated.

PMID- 8270448
TI  - Radiotherapy for carcinoma-in-situ of the glottic larynx.
AB  - PURPOSE: To describe the long-term results of radiotherapy as treatment for
      carcinoma-in-situ of the glottic larynx. METHODS AND MATERIALS: Twenty-nine
      patients with a histologic diagnosis of carcinoma-in-situ (CIS) of the true vocal
      cord were treated in the Department of Radiation Oncology at Stanford University
      Medical Center over a 32-year period from 1958-1990. Twenty patients were treated
      at the time of initial diagnosis following biopsy only (12) or vocal cord
      stripping (8) and the remainder were referred for treatment of recurrent CIS
      following one or more prior surgical procedures. Treatment was delivered with
      megavoltage equipment to a total dose of 53-66.5 Gy (mean 62 Gy) in 180-250 cGy
      fractions. The mean follow-up time is 10 years, with a range of 2-27 years.
      RESULTS: Two patients relapsed locally. One patient had recurrent CIS 5 months
      after radiotherapy and was salvaged with vocal cord stripping. The other
      developed microinvasive squamous cell carcinoma and underwent total laryngectomy.
      The actuarial freedom from local relapse and overall survival at 10 years are 92%
      and 64%, respectively. No local failures occurred more than 5 years after
      treatment. Late complications from radiotherapy were rare, and voice quality was
      good-to-excellent in 90% of patients. The actuarial risk of a second
      aerodigestive tract malignancy is 11% at 10 years. CONCLUSION: Radiation therapy
      is an effective and safe treatment modality for carcinoma-in-situ of the glottic
      larynx. Long-term local control is achieved in approximately 90% of patients with
      75% having normal voice.

PMID- 8270449
TI  - Helium charged particle radiotherapy for meningioma: experience at UCLBL.
      University of California Lawrence Berkeley Laboratory.
AB  - PURPOSE: Evaluate the use of helium charged particle radiotherapy in the
      treatment of residual or unresectable meningioma adjacent to critical structures.
      METHODS AND MATERIALS: Twenty-nine patients with meningioma of the skull base or
      spine were irradiated with helium charged particle radiotherapy at the University
      of California Lawrence Berkeley Laboratory (UCLBL) during the period 1981-1992.
      Twenty-six patients were treated for intracranial and three for spinal tumors.
      Total doses of 53.0-80.4 Gray equivalent (GyE) with a mean of 63 GyE were
      delivered using the helium ion beam. RESULTS: Ten-year local control and survival
      rates calculated by the Kaplan-Meier product limit method were 84% and 80%
      respectively. Doses of 60.0 GyE were delivered with a low rate of complications.
      The only failures were in massive, recurrent tumors. CONCLUSION: High doses using
      helium charged particle radiotherapy can be safely and effectively delivered to
      large residual or unresectable meningioma near radiosensitive structures.

PMID- 8270450
TI  - Ultrasound guided placement of transperineal prostatic afterloading catheters.
AB  - PURPOSE: A new method of performing temporary prostate brachytherapy which does
      not require an open laparotomy is described. METHODS AND MATERIALS: This
      procedure allows dynamic visualization of the placement of 13-gauge (I-125) or 17
      gauge (Ir-192) afterloading catheters into the prostate gland via saggital
      ultrasound imaging. The image enables visualization of the entire path of the
      catheter as well as cephalad gland movement. The prostate gland, seminal
      vesicles, bladder neck, urethra, and rectum are easily identified and implanted,
      if desired, during the procedure. This procedure has been used in 34 patients as
      an interstitial boost for locally advanced (T2b, T3) prostatic carcinoma
      following external beam therapy as a means to safely deliver higher doses to the
      gland. Another eight patients have undergone this procedure as salvage following
      failure of prior radical prostatectomy or external beam therapy. RESULTS: Very
      customized dosimetry has been obtained using this technique as a result of the
      optimal catheter placement achieved under ultrasound guidance, particularly with
      I-125. Although it is too early to evaluate efficacy, the procedure has been well
      tolerated and is associated with minimal morbidity to date. CONCLUSION: This new
      procedure seems to be an excellent means of safe delivery of higher doses to the
      gland compared to conventional external beam therapy. Due to the ability to cover
      the seminal vesicles as well as the afterloading nature of this procedure, a more
      customized implant is obtained relative to most permanent techniques, and open
      laparotomy is not required.

PMID- 8270451
TI  - Defining treatment margins for six field conformal irradiation of localized
      prostate cancer.
AB  - PURPOSE: To define the "ideal margins" to be used for the delivery of six-field
      conformal radiotherapy for localized prostate cancer. METHODS AND MATERIALS: For
      a typical patient, 3-D based 6-field conformal treatment plans were generated
      using uniform margins ranging from 0.5-2.5 cm (in 0.25 cm increments). In a step
      wise fashion the minimum margins required to encompass the gross tumor volume
      within the 90% isodose shell were identified. Additional margins were then added
      to account for extracapsular penetration, setup and patients movement error as
      well as for organ movement. Assumptions about the relative tolerance of
      surrounding normal tissues were also incorporated into the final decisions
      regarding margins. RESULTS: For the various areas of interface, between the
      prostate and surrounding normal tissues "ideal margins" varied from 0.75-2.25 cm.
      CONCLUSION: The use of nonuniform "ideal margins" appears to insure adequate
      coverage of the tumor, while minimizing the volume of surrounding dose limiting
      normal tissues irradiated. This approach should in theory improve the tumor
      control and complication probabilities compared to using conventional treatment
      techniques and to using a 6-field conformal technique with uniform margins.

PMID- 8270452
TI  - Three-dimensional treatment planning of intracavitary gynecologic implants:
      analysis of ten cases and implications for dose specification.
AB  - PURPOSE: Results of 3-dimensional treatment planning for ten intracavitary
      gynecologic implants and implications for dose specification are presented.
      METHODS AND MATERIALS: Using a computed tomographic (CT) compatible intracavitary
      applicator we have performed CT scans during gynecologic brachytherapy in 10
      cases. A CT-based treatment planning system with 3-dimensional capabilities was
      used to calculate and display dose in three dimensions. Conventional point doses
      including the estimated bladder and rectal maximum doses and dose to Point A were
      acquired from orthogonal simulation films. CT maximum bladder and rectal doses
      and minimum cervix doses were ascertained from isodose lines displayed on
      individual CT images. Dose volume histograms for the bladder, rectum and cervix
      were generated and used to obtain volume of the cervix target volume receiving
      less than the prescribed dose and the volume of bladder and rectum receiving more
      than the orthogonal maximum doses. The 5 cc volume of bladder and rectum
      receiving the highest dose were also calculated. RESULTS: Average values of CT
      point doses and volumes are compared with the traditionally obtained doses. As
      demonstrated by others, much higher bladder and rectal doses are found using the
      CT information. The minimum dose to the cervix target volume is lower than the
      dose to Point A in each case. CT maximum bladder and rectum and minimum cervix
      target doses may not be the best index doses to correlate with outcome because of
      the small volumes receiving the dose. CONCLUSION: We hypothesize that clinically
      useful bladder, rectal and cervix target volume doses will include volume
      information which is obtainable with dose volume histogram analysis.

PMID- 8270453
TI  - Importance of in vivo dosimetry as part of a quality assurance program in
      tangential breast treatments.
AB  - PURPOSE: The investigation of the accuracy and reproducibility in the daily dose
      delivered in tangential breast treatments with in vivo dose measurements. METHODS
      AND MATERIALS: In vivo dose measurements performed on the tangential treatment
      fields of 35 breast cancer patients are analysed for three units: a 6 MV linear
      accelerator, an old Cobalt unit and a new Cobalt unit. The results are plotted in
      frequency distributions. Deviations on the mean are often the expression of a
      systematic error in one of the core procedures of a department. A large spread of
      the results around the mean indicates a high burden of random set-up errors
      and/or systematic errors in individual patients. The reproducibility in dose
      delivery is studied by comparing repetitive checks to their respective mean for
      investigation of random day-to-day variation. RESULTS: A small systematic error
      on the entrance dose (+ 1.4%) is detected on the old Cobalt unit due to a
      discrepancy between measured and published percentage depth dose values. An
      unexpected systematic overdosage (+ 6%) is detected after implementation of a new
      software for dose calculation, proving that treatment quality is a process
      needing continuous monitoring. The transmission measurements demonstrate a
      systematic error in dose delivery of 1.5 to 3% due to the assumption that the
      breast is water equivalent when calculating the dose. The large spread of the
      transmission measurements (sa = 7.7%) shows that the weakest point in the
      treatment preparation chain is inaccurate acquisition of external body contours,
      leading to systematic errors in dose delivery for specific patients. The standard
      deviation for the reproducibility is 3.1% for the old Cobalt unit, vs. 1.6% on
      the other units, demonstrating the influence of staffing and mechanical
      characteristics of the units on daily precision in dose delivery. CONCLUSION: In
      vivo dosimetry is an important tool in a departmental quality assurance program
      to detect systematic errors in dose delivery, to identify inadequate treatment
      situations, to investigate weak points in the chain of treatment preparation and
      to ensure accurate dose delivery for individual patients. The predictive value of
      a single check for the accuracy in dose delivery during the whole treatment
      series is high for reproducible treatment methodologies.

PMID- 8270454
TI  - Electron arc therapy of the postmastectomy prosthetic breast.
AB  - PURPOSE: Reconstructive surgery of the postmastectomy breast presents new
      challenges to postoperative radiation therapy. This paper evaluates the
      dosimetric significance of oblique incidence of the electron field on the
      reconstructed mound during arc therapy. METHODS AND MATERIALS: Using film
      densitometry, the relative dose distributions resulting from electron arc therapy
      incident on phantoms simulating the breast and chest wall dimensions of an actual
      patient are evaluated. RESULTS: Irradiation of the breast phantom in normal
      supine position results in constriction of the dose distribution at the junction
      of the reconstructed mound with the chest wall. Angulation of the phantom to
      provide a more normal incidence of the electron beam during arc reduces the
      constriction by minimizing obliquity of the incident electrons. CONCLUSION: These
      measurements suggest that, with proper positioning of the patient relative to the
      incident electron beam, electron arc therapy may be used as an alternative
      treatment technique for treatment of the postmastectomy reconstructed breast and
      chest wall.

PMID- 8270455
TI  - Rate of relapse following treatment for localized prostate cancer: a critical
      analysis of retrospective reports.
AB  - PURPOSE: Controversy exists over the optimal treatment for patients with
      clinically localized prostate cancer. Almost all of the treatment results are
      from non-randomized trials and interseries comparison is difficult since the
      apparent success of a treatment, as judged by the actuarial freedom from relapse
      and survival data, depends on patient selection criteria and post-treatment
      evaluation, in addition to the efficacy of the therapeutic intervention. In this
      report the calculation of a hazard function is used to estimate and compare the
      rate of relapse for the different treatments. METHODS AND MATERIALS: Clinical
      reports from major surgery and radiation oncology treatment institutions were
      analyzed. The actuarial recurrence data were used to calculate the annual rate of
      recurrence within each series. RESULTS: For all but the lowest volume tumors,
      patients continue to be at risk of relapse for as long as these series have been
      followed. Despite the heterogeneity of patient populations, the recurrence rates
      by stage are similar for patients treated with surgery or irradiation. This
      result is consistent with pathologic data from prostatectomy specimens which
      indicate that for lesions > 12 cm3 (approx. 3 cm in diameter) there is high
      likelihood of extraprostatic disease. CONCLUSION: Treatment outcome for patients
      with localized prostate cancer may be more dependent on the inherent tumor
      biology than the particular type of treatment. Accordingly, the expectation and
      recommendation of a treatment must take into consideration the continued risk of
      relapse with either radiation therapy or surgery. There are, as yet, insufficient
      data regarding the impact of screening and earlier diagnosis on the curability of
      patients with localized prostate cancer.

PMID- 8270456
TI  - A review of neoadjuvant chemotherapy for head and neck cancer: partially shrunken
      tumors may be both leaner and meaner.

PMID- 8270457
TI  - Three-dimensional conformal radiation therapy in locally advanced carcinoma of
      the prostate: preliminary results of a phase I dose escalation study.

PMID- 8270458
TI  - Patterns of Care and RTOG studies in prostate cancer: long-term survival, hazard
      rate observations, and possibilities of cure.
AB  - PURPOSE: This study was undertaken to show the long-term survival and probability
      of cure of prostate cancer patients treated with external beam radiation in USA
      national surveys and in the prospective clinical trials of the RTOG. METHODS AND
      MATERIALS: Two national patterns of care surveys of patients treated in 1973 and
      1978 are reported along with two RTOG prospective trials (7506 and 7706). Hazard
      rates represent the risk of death and are compared to the rate expected for a
      normal population. RESULTS: For patients with Stage A cancers, the survival is
      not different from the expected survival for any of the reported surveys. The
      hazard rate for death does not significantly exceed the expected hazard rate out
      to 15 years. For patients with Stage B cancer, there is a decrease in survival
      below expected and hazard rates show a continuing excess mortality as long as 15
      years after treatment. For patients with Stage C cancers, there is a more rapid
      decrease in survival that then becomes parallel to the expected survival. Hazard
      rates indicate there has been a return to expected mortality at 15 years.
      CONCLUSION: These data make a strong argument for the long-term cure of prostate
      cancer by external beam radiation, and support the continued use and study of
      radiation therapy as a curative modality in prostate cancer. No similar national
      data is available for any other method of management.

PMID- 8270459
TI  - Photon versus fast neutron external beam radiotherapy in the treatment of locally
      advanced prostate cancer: results of a randomized prospective trial.
AB  - PURPOSE: To evaluate the effectiveness of fast neutron radiation therapy in
      treatment of locally advanced carcinomas of the prostate. METHODS AND MATERIALS:
      From April 1986 to October 1990, 178 patients were entered on a prospective,
      multi-institutional randomized study of the NCI-sponsored Neutron Therapy
      Collaborative Working Group. This trial compared external beam photon irradiation
      (7000-7020 cGy) with external beam neutron irradiation (2040 ncGy) for patients
      with high-grade T2 or T3-4, N0-1, M0 adenocarcinomas of the prostate. Eighty-nine
      patients were randomized to each treatment. Six patients were subsequently judged
      to be ineligible, leaving 85 photon and 87 neutron randomized patients eligible
      for analysis. RESULTS: With a follow-up time ranging from 40 to 86 months (68
      months median follow-up) the 5-year actuarial clinical local-regional failure
      rate for patients treated with neutrons was 11%, vs. 32% for photons (p < 0.01).
      Incorporating the results of routine posttreatment prostate biopsies, the
      resulting "histological" local-regional tumor failure rates were 13% for neutrons
      vs. 32% for photons (p = 0.01). To date, actuarial survival and cause-specific
      survival rates are statistically indistinguishable for the two patient cohorts,
      with 32% of the neutron-treated patient deaths and 41% of the photon-treated
      patient deaths caused by prostate cancer (p = n.s.). Prostate specific antigen
      (PSA) values were elevated in 17% of neutron-treated patients and 45% of photon
      treated patients at 5 years (p < 0.001). Severe late complications of treatment
      were higher for the neutron-treated patients (11% vs. 3%), and were inversely
      correlated with the degree of neutron beam shaping available at the participating
      institutions. Neutron treatment delivery utilizing a fully rotational gantry and
      multileaf collimator did not result in an increase in severe late effects when
      compared to photon treatment. CONCLUSION: High energy fast neutron radiotherapy
      is safe and effective when adequate beam delivery systems and collimation are
      available, and it is significantly superior to external beam photon radiotherapy
      in the local-regional treatment of large prostate tumors.

PMID- 8270460
TI  - Improved local control and survival for surgically staged patients with locally
      advanced prostate cancer treated with up-front low dose rate iridium-192 prostate
      implantation and external beam irradiation.
AB  - PURPOSE: In an effort to improve upon the historically poor local control and
      survival rates for locally advanced prostate carcinoma, a prospective
      multidisciplinary clinical trial was initiated using low dose rate Iridium-192
      prostate implantation and external beam irradiation. METHODS AND MATERIALS:
      Between January 1983 and September 1989, 57 patients with newly diagnosed bulky
      prostatic carcinoma (5 Stage B2, 52 Stage C) were treated at the Mayo Clinic (34
      patients) and William Beaumont Hospital (23 patients) with (a) 5 Gy delivered
      preoperatively in one fraction, (b) pelvic lymphadenectomy with interstitial
      implantation of the prostate using Iridium-192 seeds via a perineal template to
      30-35 Gy, and (c) 30.6 Gy external irradiation to prostate only in 17 fractions.
      RESULTS: After lymphadenectomy, 30/57 (53%) patients had pathologically confirmed
      positive lymph nodes or "D1" disease. Thirty-four patients (60%) had Gleason
      scores > or = 7. Mean age at diagnosis was 63.3 years. Median overall follow-up
      was 72 months. The 5-year actuarial survival rate was 85% and disease-free
      survival was 63%. The 5-year survival for patients with negative nodes was 93%
      and with positive nodes was 79%. The corresponding survival for patients with
      Gleason scores < or = 6 was 96% and > or = 7 was 78%. Multivariate analysis
      demonstrated that of all covariates considered, only Gleason score had prognostic
      significance for disease-free survival (p < 0.05) and no covariates were
      statistically significant for overall survival. Thirty-nine of the 57 patients
      had a prostatic re-biopsy performed at 18 months. Pathologically confirmed local
      control was ultimately achieved in 31/39 (79.5%). There was no difference in
      survival in patients with positive re-biopsies vs. those with negative results.
      The 5-year actuarial rate of clinical local control was 94%. Three patients
      clinically failed locally and 21 demonstrated distant progression. The median
      time to progression was 34 months. Nineteen percent received some form of
      hormonal manipulation at the time of their treatment course and an additional 42%
      were treated with hormones during their follow-up period, primarily after distant
      failure. The grade 4 rectal ulceration rate decreased to 4.5% with modification
      of the brachytherapy technique. Three patients experienced grade 4 urinary
      incontinence and three patients experienced grades 3 or 4 chronic perineal pain.
      CONCLUSION: These results indicate that bulky prostate carcinoma can be
      successfully controlled locally by this novel and aggressive approach with
      moderate toxicity and improved survival.

PMID- 8270461
TI  - The effects of local and regional treatment on the metastatic outcome in
      prostatic carcinoma with pelvic lymph node involvement.
AB  - PURPOSE: The effect of local and regional treatment on the development of distant
      metastases in patients with localized node negative and node positive carcinoma
      of the prostate is examined. METHODS AND MATERIALS: Distant metastases-free
      survival was evaluated in 1078 patients with Stage B-C node negative (733
      patients) or node positive (345 patients) carcinoma of the prostate, staged with
      pelvic lymph node dissection and treated with retropublic 125I implantation at
      the Memorial Sloan-Kettering Cancer Center between 1970 and 1985. RESULTS: The 15
      year actuarial distant metastases-free survival rate for the entire group of
      patients was 27%. Lymph node involvement was the most significant covariate
      affecting distant metastases-free survival, although local failure, stage, and
      grade were also independent variables. Distant metastases-free survival varied
      with the extent of lymph node involvement (N0 vs. N1, p < 0.0001; N1 vs. N2, p <
      0.0001). However, the difference between N1 and N2 patients was due to a faster
      rate of development of distant metastases in N2 patients. The ultimate 10-year
      distant metastases-free survival rate was similar for the two patient groups (11%
      for N1 and 9% for N2). Local failure correlated with the metastatic outcome in
      patients with B-C/N0 disease (p < 0.00001), but not in N1 or N2 patients.
      Although distant metastases-free survival in locally controlled N1 patients was
      improved compared to N2 patients (p = 0.004), when stratified by primary tumor
      stage and grade, the differences were no longer significant. CONCLUSION:
      Essentially all node positive patients with carcinoma of the prostate will
      develop distant metastatic disease if followed for sufficiently long periods of
      time. This is consistent with the hypothesis that in such patients distant
      micrometastatic dissemination already exists at the time of initial diagnosis.
      The data suggest that clinical trials designed to test whether improvements in
      local therapy impact on survival should be restricted to node negative patients.
      The data also raise concerns regarding the therapeutic value of elective whole
      pelvic irradiation.

PMID- 8270462
TI  - Radiation induced height impairment in pediatric Hodgkin's disease.
AB  - PURPOSE: To quantitate the impairment in skeletal growth from radiation
      treatment, we reviewed height measurements among children with Hodgkin's disease
      irradiated at Stanford University Medical Center between 1965 and 1986. METHODS
      AND MATERIALS: One hundred and twenty-four children with Hodgkin's disease, in
      whom long-term follow-up data were available, became the subjects for this
      analysis. They all had baseline height measurements within 1 year of radiation
      treatment, a final height measurement beyond age 15 for boys and 13 for girls,
      and a minimum time interval between baseline and final measurement of 2 years. A
      baseline and final percent height, as compared to a reference standard, was
      calculated for each patient. The difference between these two figures was used to
      assess height impairment. The study group was divided into age and treatment
      groups and a comparative analysis between these groups was performed. RESULTS:
      Height impairment was most severe among children who were given high dose
      radiation to the entire spine when pre-pubertal in age. These patients
      demonstrated a 7.7% (p < 0.0001) average height impairment, which equates to a
      height loss of 13 cm or two standard deviations of the U.S. population mean.
      Pubertal and post-pubertal patients given similar heavy treatment as well as pre
      pubertal patients given light treatment also demonstrated some impairment of
      skeletal growth, however, the loss was not deemed clinically significant.
      Comparison of standing versus sitting height impairment did not show evidence of
      disproportionate final growth impairment. CONCLUSION: Treatment regimens that use
      low doses of radiation for pediatric Hodgkin's disease are thus not associated
      with clinically significant impairment of skeletal growth, as measured by
      standing and sitting heights.

PMID- 8270463
TI  - Computed tomography assessment of splenic size as a predictor of splenic weight
      and disease involvement in laparotomy staged Hodgkin's disease.
AB  - PURPOSE: To evaluate how well splenic size predicts the risk of splenic Hodgkin's
      disease and to assess how accurately splenic dimensions on computerized
      tomographic scans predict spleen size and involvement by Hodgkin's disease.
      METHODS AND MATERIALS: Splenic weights were obtained from laparotomies performed
      on 897 patients who presented with Hodgkin's disease and were compared with
      histologic involvement using logistic regression. Splenic dimensions were
      measured from preoperative computerized tomographic scans in 94 of these
      patients, and unidimensional splenic measurements [length (L), width (W),
      thickness (T)] and their products were compared with splenic weight at laparotomy
      using linear regression. RESULTS: Hodgkin's disease involved 42% of the spleens
      at laparotomy and 31% of those assessed by computerized tomography. Splenic
      weight averaged 198 +/- 5 g (range 40-2000 g). Weight and involvement were
      greater with "unfavorable" histologies (mixed cellularity, lymphocyte depletion,
      and unclassified Hodgkin's disease: 229 +/- 12 g; 62.7% involved) than with
      "favorable" histologies (nodular sclerosing, lymphocyte predominant, and
      interfollicular Hodgkin's disease: 191 +/- 5 g; 37.8% involved). Splenic weight
      was the strongest independent risk factor correlated with Hodgkin's disease in
      univariate and multivariate analyses in all patients and the only identifiable
      univariate risk factor among those with computerized tomographic scans. For most
      patients, however, splenic weight poorly predicted involvement: The probability
      of involvement never fell below 20% and exceeded 80% when splenic weight exceeded
      270 g with unfavorable histologies or 685 g in favorable histologies. Spleens of
      average weight had a probability of involvement of 36% with favorable
      histologies, 70% with unfavorable histologies. Unidimensional measurements of the
      spleen on computed tomography correlated poorly with splenic weight, but their
      product correlated well (Correlation coefficients: L: 0.73; W: 0.65; T: 0.78;
      [0.344485 x L x W x T]: 0.94). CONCLUSIONS: Splenic weight is the strongest
      factor correlating with the risk of splenic involvement by Hodgkin's disease and
      can be accurately estimated from three-dimensional measurements on computed
      tomographic scans, but not from unidimensional measurements. However, splenic
      weight is not a sensitive predictor of involvement of the spleen by Hodgkin's
      disease. Therefore, treatment approaches to Hodgkin's disease must be based upon
      intermediate risks of splenic involvement for most clinically staged patients.

PMID- 8270464
TI  - Ultrastructural and biochemical observations on proteoglycans and collagen in the
      mutable connective tissue of the feather star Antedon bifida (Echinodermata,
      Crinoidea).
AB  - Mutable connective tissue, unique to echinoderms, changes its mechanical
      behaviour within seconds of nervous stimulation. The molecular mechanism of this
      phenomenon is not understood. In this study proteoglycans and collagen of the
      brachial ligaments connecting neighbouring ossicles of the arms of the feather
      star Antedon bifida have been investigated by biochemistry, light and electron
      microscopy and the critical electrolyte concentration (CEC) technique using the
      dye Cupromeronic Blue (CB). The ligaments consist mainly of parallel cross
      striated collagen fibrils, 82 +/- 12 nm in diameter, with a characteristic
      banding pattern and a D-period of 52.8 +/- 3.2 nm. Some fibrils were
      disaggregated into bundles of 10-11 nm protofibrils, lying between the normal
      fibrils. Proteoglycans occur at the surface of the fibrils with 2 binding sites
      (each with a different CEC) per D-period and also inside the fibrils. The surface
      proteoglycans are more highly sulphated (i.e. their CECs are > 1.3 M) than the
      intrafibrillar proteoglycans (CEC < 0.9 M). The glycosaminoglycans consist of a
      highly sulphated chondroitin sulphate, possibly with fucose residues. The results
      are consistent with the theory that disaggregation of the fibrils into
      protofibrils and reaggregation might be a mechanism of mutability, without
      excluding the possibility that fibrils may slide alongside each other during
      movements in the viscous phase of the ligament.

PMID- 8270465
TI  - Fine structure of the middle ear epithelium in the chicken (Gallus gallus).
AB  - The epithelium lining the tympanic cavity of the chicken possesses distinct
      morphological characteristics. Its ultrastructure was studied using 2 preparative
      techniques. (1) After fixation in Karnovsky's solution, postfixation in osmium
      tetroxide and embedding in Epon, the epithelium was observed to contain 2 kinds
      of cell: secretory and basal. The secretory cells (which we refer to as mixed
      granulated cells) showed numerous secretory vesicles that varied in appearance,
      some containing paracrystalline formations. The basal cells, located close to the
      basement membrane, showed no evidence of secretory activity. (2) Other specimens
      were immersed in Karnovsky fixative and subsequently in a mixture of
      glutaraldehyde and tannic acid. They were then osmicated and embedded in polar
      Epon mix. With this method, the epithelium was seen to be covered by electron
      dense material made up of thin intertwined tubules. In addition, the secretory
      cells contained vesicles with concentrically arranged lamellae; such vesicles
      resembled the multilamellar bodies of mammalian type II pneumocytes. The
      hypothesis is advanced that tubules and lamellar vesicles are related to the
      presence of surfactant substances.

PMID- 8270466
TI  - Cell death and phagocytosis of haematopoietic elements at the onset of
      haematopoiesis in the mouse spleen: an ultrastructural study.
AB  - The spleen in fetal and early postnatal mice contains a variety of proliferating
      haematopoietic cells as well as 2 kinds of phagocytes, scavenger macrophages and
      mast cells, laden with large heterogeneous inclusions. Their phagocytotic
      activity is directed towards extruded erythrocyte nuclei, erythrocytes and dying
      haematopoietic cells. The splenic cords after 18 d of gestation become filled
      with proliferating haematopoietic cells, and the cords contain a small number of
      free haematopoietic cells undergoing degeneration. The early signs of cell death
      can be observed in the nuclear structures: hyperchromasia of the nuclear membrane
      or nuclear dissolution. Erythroblast nuclei are amongst the most frequent
      elements engulfed. Phagocytes also take up and digest degenerating blood cells,
      i.e. erythrocytes, erythroblasts and neutrophil granulocytes. Since the digestion
      processes are ultrastructurally different for the various haematopoietic
      elements, the origins of heterolysosomes enclosed by phagocytes can be identified
      by electron microscopy. Mast cells, originally classified as secretory cells,
      phagocytose erythroid line cells in the spleen. Cell death in several
      haematopoietic cell lines is discussed in relation to programmed cell death in
      the developing spleen.

PMID- 8270467
TI  - Eyelid development, fusion and subsequent reopening in the mouse.
AB  - The process of eyelid development was studied in the mouse. The critical events
      occur between about 15.5 d postcoitum (p.c.) and 12 d after birth, and were
      studied by conventional histology and by scanning electron microscopy. At about
      15.5 d p.c. the cornea of the eye is clearly visible with the primitive eyelids
      being represented by protruding ridges of epithelium at its periphery. Over the
      next 24 h, eyelid development proceeds to the stage when the cornea is completely
      covered by the fused eyelids. Periderm cells stream in to fill the gap between
      the developing eyelids. Their proliferative activity is such that they produce a
      cellular excrescence on the outer surface of the line of fusion of the eyelids.
      This excrescence had almost disappeared by about 17.5 d p.c. Keratinisation is
      first evident at this stage on the surface of the eyelids and passes continuously
      from one eyelid to the other. Evidence of epidermal differentiation is more
      clearly seen in the newborn, where a distinctive stratum granulosum now occupies
      about one third of its entire thickness. Within the subjacent dermis, hair
      follicles are differentiating. By about 5 d after birth, a thick layer of keratin
      extends without interruption across the junctional region. While a noticeable
      surface indentation overlies the latter, a similar depression is only seen on the
      conjunctival surface by about 10 d after birth. Keratinisation is also observed
      to extend in from the epidermal surface to involve the entire region between the
      2 eyelids at about this time.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270468
TI  - Lymphatic drainage from the distal small intestine in sheep.
AB  - Lymphatic drainage from the wall of the distal small intestine, important
      especially in young sheep as a major site of gut-associated lymphoid tissue,
      begins with a series of longitudinally oriented subserosal vessels. These vessels
      convey lymph to the mesenteric border of the intestinal wall and unite to form
      larger vessels which course through the mesentery to the mesenteric lymph nodes.
      These nodes lie towards the periphery of a broad, fan-shaped mesentery, adjacent
      to major arteries and veins. Mesenteric vessels convey lymph from the jejunum and
      part of the proximal ileum to the jejunal nodes. Lymph from most of the ileum is
      conveyed to caecal nodes. The larger mesenteric lymphatics have well formed
      smooth muscle and connective tissue layers surrounding the endothelium. They are
      often adjacent to, but rarely within, the connective tissue band anchoring the
      major arteries and veins to one or both lamellae of mesentery. Few anastomoses
      occur between vessels from opposing sides of the gut wall or the mesentery.
      Afferent lymphatics enter the subcapsular and trabecular sinuses of the nodes
      over most surfaces apart from the hilar region. Lymph flows through cortical
      tissue to the medulla, which occupies most of the node. In the medulla, sinuses
      occur within medullary cords as well as between them. Initial efferent lymphatics
      occur throughout medullary tissue. Efferent vessels emerge at a hilus then
      coalesce and drain into the jejunal or ileal trunk. The hilus of the node varies
      from a flat, poorly defined area on the lesser curvature, to a depression or
      groove. The latter commonly occurs in elongated jejunal nodes.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8270469
TI  - Distribution of pacinian corpuscles in the hand of the monkey, Macaca fuscata.
AB  - The size and distribution of pacinian corpuscles were investigated in the palmar
      aspect of both hands of the monkey, Macaca fuscata. Most pacinian corpuscles were
      located in the dermis (dermal type) and subcutaneous tissue (subcutaneous type)
      throughout the hand. On light microscopy there were no differences in the
      structure of these 2 types, although almost all the subcutaneous type had a
      greater longitudinal dimension than the dermal type. Corpuscles were oval or
      elliptical and their longitudinal and transverse dimensions varied from 156 to
      2025 microns and 88 to 1240 microns, respectively. Many pacinian corpuscles were
      in close relation to the small blood vessels, and their diameters were as large
      as those of capillaries. There were 458 corpuscles (dermal type: subcutaneous
      type = 140:318) in the right hand and 416 (186:230) in the left hand. About 40%
      of the corpuscles in each hand were found in the digital region; the remainder
      were located in the palm. The mean number of corpuscles in each finger was 33 and
      they were concentrated in the distal and middle phalanges. In the palmar region,
      most corpuscles were localised in the 2nd and 3rd interdigital eminences and the
      thenar and hypothenar eminences.

PMID- 8270470
TI  - Purkinje cell complements in mammalian cerebella and the biases incurred by
      counting nucleoli.
AB  - An unbiased stereological counting device (the fractionator) was used to count
      Purkinje neurons in mammalian cerebella of known weights in order to define the
      relationship between weight and number. Nucleoli were chosen as the counting unit
      and numbers were estimated from uniform random samples of wax-embedded tissue
      sections. For the cerebella of rat, rabbit, cat, dog, goat, sheep, pig, ox, horse
      and human, there was a significant linear relationship between log number and log
      weight. The allometric relationship took the form N = 748,500 x W0.627. The
      relative bias associated with using nucleoli as counting units was assessed
      separately on disector pairs of sections and amounted to roughly -5% but varied
      between species. When the brains of females and males were analysed separately
      (cat, goat, pig, ox, horse, human), there were no significant differences between
      the regression lines. These results are consistent with earlier findings. They
      imply that Purkinje neuron packing densities decrease as brain size increases.
      Moreover, our preliminary findings appear to indicate that, for any given
      cerebellar weight, females and males have similar numbers of neurons.

PMID- 8270471
TI  - Rare origin of the obturator, inferior epigastric and medial circumflex femoral
      arteries from a common trunk.
AB  - Two cases of arterial variation are described in which the obturator, inferior
      epigastric and medial circumflex femoral arteries arose from a common trunk from
      the external iliac artery. A possible ontogenetic explanation is provided.

PMID- 8270472
TI  - Anatomical variation of the insertion of scalenus anterior in adult human
      subjects: implications for clinical practice.
AB  - The frequency of an abnormally anterior insertion of scalenus anterior to the
      scalene tubercle on the superior aspect of the 1st rib was examined as a possible
      contributory factor to venous compression syndromes and to difficulties in
      cannulation of the subclavian vein. The insertion of scalenus anterior was
      exposed bilaterally in 21 adult cadavers and its position determined. The
      position of the scalene tubercle was also determined in a sample of 50 dried 1st
      ribs. The results were normalised for height. Three of the cadavers had position
      values that were above or at the upper point of the 95% confidence limits for the
      sample, indicating an abnormally anterior insertion. Two dried 1st ribs had
      values just below the lower 95% confidence limits, implying an abnormally
      posterior position. In the 3 cadavers with an abnormally anterior position, the
      subclavian artery and vein followed an abnormally anterior and inferior course
      with respect to the clavicle, and in 1 the subclavian vein was stenosed
      bilaterally at the costoclavicular angle. An abnormally anterior insertion of
      scalenus anterior may be a cause of venous compression syndromes in the root of
      the neck and give rise to difficulties when undertaking cannulation of the
      subclavian vein.

PMID- 8270473
TI  - The orbital glands of the terrapin Pseudemys scripta in response to osmotic
      stress: a light and electron microscope study.
AB  - The histochemical and ultrastructural features of both orbital glands--the
      anterior lacrimal and harderian glands--were compared in the terrapin Pseudemys
      scripta following adaptation either to distilled water or to seawater. Seawater
      adaptation activated the harderian gland and caused a major structural
      reorganisation. Type I cells increased in number, whereas type II cells became
      smaller and less numerous. The most striking change was shown by the type IV
      cells which display the features of a salt-secreting cell. This cell type
      increased in number and changed from a unicellular form to multicellular
      complexes. Transfer from fresh water to distilled water caused a decrease in
      alcianophilia in type I and type III glandular cells and degenerative phenomena
      were often seen in type I and type IV cells. The anterior lacrimal gland showed
      only minor changes either in distilled or seawater adapted terrapins. Transfer to
      distilled water also caused degenerative phenomena in the lacrimal gland. These
      results establish for the first time the involvement of the harderian gland of a
      terrapin in osmoregulation.

PMID- 8270474
TI  - The presence of paraganglia in the human ascending aortic fold: histological and
      ultrastructural studies.
AB  - Light and electron microscopic features of the human ascending aortic fold are
      described. Histological examination showed the characteristic epicardial
      structures continuous with a stroma of abundant adipose tissue. In addition,
      randomly distributed tissue resembling the carotid body was observed by both
      light and electron microscopy throughout postnatal life, from a fullterm
      stillborn fetus to the oldest subject (65 y). The size of the paraganglionic cell
      nests was variable at all ages. The presence of paraganglia in the aortic fold
      raises the possibility that they are concerned with chemoreception.

PMID- 8270475
TI  - Gonadal development in the opossum, Monodelphis domestica: the rete ovarii does
      not contribute to the steroidogenic tissues.
AB  - The gonads of 273 animals, ranging in age from newborn to adult, were examined in
      serial histological sections. Primordial germ cells were located in the hindgut,
      dorsal mesentery and gonadal primordia of neonates but were alkaline phosphatase
      negative. The testis differentiated between d 13 of gestation and birth, about
      half a day later. Testis cords, composed of pre-Sertoli cells and containing germ
      cells, were distributed peripherally in the gonad. Ovarian differentiation began
      on d 6, when an ill defined cortex and medulla became discernible. Meiosis
      commenced on d 14, medullary cords formed from blastema cells by d 26 and gave
      rise to granulosa cells around d 29. The rete ovarii was first observed in the
      hilar region of the gonad primordium. It penetrated maximally two thirds of the
      ovarian length between d 26 and d 29. It is concluded that, at least postnatally,
      the mesonephros does not contribute to the rete ovarii and that the granulosa
      cells are derived not from the rete but from the medullary cords.

PMID- 8270476
TI  - A light and electron microscopic quantitative analysis of the innervation of
      axillary lymph nodes in juvenile and old rats.
AB  - The innervation of axillary lymph nodes from 20 juvenile rats (aged < 6 wk) was
      compared with that of 20 old rats (aged > 2 y). One half of each group was
      investigated by light microscopy on silver-impregnated paraffin sections, the
      other half by electron microscopy. The lymph nodes of the old animals were larger
      than those of juvenile animals, as derived from the volumes analysed by light
      microscopy. By both light and electron microscopy, the nerves were found to be
      confined almost exclusively to the medulla and were frequently associated with
      groups of plasma cells. Nerves identified as cortical in location were
      consistently found only in cortical areas adjacent to the medulla. In the old
      animals the nerves were thicker and more prominent in the light microscopic
      preparations. No such differences were noted at the ultrastructural level.
      Myelinated nerves were found in all lymph nodes, except in a single old animal.
      Quantitative analysis of the nerves revealed a significant increase in the
      density of innervation of the medulla in the old animals both by light and
      electron microscopy. By light microscopy there also appeared to be a significant
      increase in the innervation density of the cortex, but these nerves were
      considered to be mislocalized because of difficulty in precise localisation at
      this level of magnification. On light microscopy, a significant increase in the
      incidence of nerve branching was found in the nodes of the old animals.

PMID- 8270477
TI  - Primordial germ cells in the primitive streak stages chick embryo as studied by
      scanning electron microscopy.
AB  - Chick embryo primordial germ cells (PGCs) at stages 4-8 were localised in the
      late hypoblast layer. PAS staining confirmed their distribution in a large arc at
      the anterior border of the area pellucida/area opaca. By scanning electron
      microscopy the PGCs were seen as spherical cells within the late hypoblast layer.
      Individual cells separated from this layer and collected in groups of 2-10 in
      shallow pockets in the hypoblast layer prior to their migration. The pockets
      containing PGCs were clearly visible by light and scanning electron microscopy
      and demarcated the germinal ridge at stages 4-8.

PMID- 8270478
TI  - The avian prechordal head region: a morphological study.
AB  - The axial mesoderm of the anterior head region was investigated in young chick
      and quail embryos by light and electron microscopy. Semithin sections showed that
      the axial head mesoderm consists of the head process and prechordal mesoderm. At
      the anterior end of the prechordal mesoderm, a group of columnar epithelial cells
      formed a pit-like structure. The bases of these columnar cells extended to the
      neural plate, thus limiting the prechordal mesoderm anteriorly. The cells lining
      the pit-like structure at its anterior end joined a cell accumulation made up of
      cells of mesenchymal character. Electron microscopy revealed that the columnar
      cells forming the pit-like structure were covered by a basal lamina which was
      discontinuous on its anterior aspect. No basal lamina was recognisable between
      the columnar epithelial cells and mesenchymal cells joining them anteriorly. The
      columnar epithelial cells bordering the prechordal mesoderm anteriorly were
      therefore assumed to be part of the endodermal germ layer. In agreement with the
      findings of other authors, it is proposed to term these axially located columnar
      cells of the endoderm the prechordal plate and to distinguish them from the
      prechordal mesoderm arising during gastrulation. For the mesenchymal cell
      accumulation anterior to the prechordal plate, participation in the formation of
      the prosencephalic mesenchyme is assumed. This implies that the definitive
      endodermal germ layer, like the ectodermal one represented by the neural crest,
      may also be able to contribute to mesenchyme formation in the head.

PMID- 8270479
TI  - Satellite cell content in muscles of large and small mice.
AB  - Quantitative analyses of the satellite cell content in the biceps brachii muscle
      of mice genetically selected for high (QL) and low (QS) bodyweight showed that
      selection alters the total number of satellite cell nuclei rather than the
      relative proportions of nuclei in the myofibre and satellite cell populations.
      These findings are in accordance with those previously published for other
      tissues of these mice and support the hypothesis that regulatory mechanisms
      remain unaltered by selection pressure. Size at birth, however, is a reflection
      of nutritional status as well as genetic background, and comparisons between
      differently sized littermates within each of the lines showed a significant
      increase in satellite cell density in larger compared with smaller individuals.
      These differences between littermates were not accompanied by any alteration in
      myofibre nuclear density. It is therefore suggested that whilst both genetic and
      nutritional factors exert their effects on muscle growth through an influence on
      satellite cell division, both do so at different stages during the programme of
      satellite cell differentiation.

PMID- 8270481
TI  - Is the analytic situation shame-producing?
AB  - The question whether the analytic situation is shame-producing has to be answered
      in an affirmative way. But it is often difficult to discern to what extent this
      is a quite natural reaction to the 'artificial inequality' of the analytic
      situation itself, of which patients so often complain. Indeed, it is also in most
      cases due to the patient's excessive susceptibility to shame and his/her
      transference feelings. Yet, on the whole, shame has an important place in the
      economy of the psyche. It can have a blocking, counterproductive influence on the
      analysis, but this is not necessarily so. Shame can be defined as a 'guardian of
      human dignity' in at least two senses. We react with shame if we are afraid of
      losing dignity 'in the eyes of others'. But shame is also aroused--at best--if we
      betray our inner integrity and truth. Although analysts should be sensitive to
      their patients' vulnerability to shame, avoiding unnecessary and
      counterproductive shaming, they still need to face issues of shame for the sake
      of the individuation process. This may result in greater self-acceptance,
      including one's shadow, and a shift may take place; we may become less fearful of
      what others think of us and more concerned to adhere to our own truth.

PMID- 8270480
TI  - Quantitative enzyme cytochemistry during human macrophage development.
AB  - Integrating microdensitometry was used to study changes in the intracellular
      activity of 4 enzymes during macrophage development. Suspension cultures of blood
      monocytes from 19 healthy human subjects were examined at 0, 2, 4 and 6 d.
      Mononuclear phagocytes were harvested by glass adherence and standard methods
      were used for cytochemical staining for NADH dehydrogenase, succinate
      dehydrogenase, acid phosphatase and alpha-naphthyl butyrate esterase. All
      specimens from all subjects were stained at the same time and staining
      intensities in individual cells were measured at appropriate wavelengths. A
      highly significant increase in enzyme activity with culture time was found for
      all 4 enzymes. These increases in mitochondrial, lysosomal and ectoenzyme
      activities during development indicate the increasing functional capabilities of
      the macrophages.

PMID- 8270482
TI  - Moving opposites in the self. A Heraclitean approach.
AB  - Theory and method are presented for the investigation of opposites in personal
      experience, with particular attention to their unification. The strategy is to
      invite people to relate actively two strongly contrasting experiences (meaning
      units) and to combine these into a third unit. Three idiographic studies are
      reported showing that the third meaning unit, created by the subjects, shifts
      towards another pair of polar opposites. This phenomenon, called the phenomenon
      of 'moving opposites', is discussed in view of the relationship between the field
      of personality and social psychology and the field of clinical psychology and
      psychotherapy. The phenomenon is also discussed with reference to Aristotle's and
      Heraclitus' conflicting views on opposites.

PMID- 8270484
TI  - Thiazohalostatin, a new cytoprotective substance produced by Actinomadura. II.
      Physico-chemical properties and structure determination.
AB  - Thiazohalostatin is a new cytoprotective substance produced by Actinomadura sp.
      HQ24. Its structure was elucidated as shown in Fig. 1 by NMR spectral analyses
      and chemical modifications. Thiazohalostatin was found to possess a novel
      skeleton containing trichloropyrrole and thiazoline ring moieties.

PMID- 8270483
TI  - Thiazohalostatin, a new cytoprotective substance produced by Actinomadura. I.
      Taxonomy, production, isolation and biological activities.
AB  - Thiazohalostatin has been isolated from the culture broth of Actinomadura sp. by
      a screening program designed to find novel cytoprotective substances. It was
      purified by use of column chromatography on silica gel, reversed phase HPLC and
      then isolated as colorless powder. Thiazohalostatin prevented cell death caused
      by calcium overload and exhibited an inhibitory activity against lipid
      peroxidation.

PMID- 8270485
TI  - Adenophostins A and B: potent agonists of inositol-1,4,5-trisphosphate receptor
      produced by Penicillium brevicompactum. Taxonomy, fermentation, isolation,
      physico-chemical and biological properties.
AB  - New inositol-1,4,5-trisphosphate (InsP3) agonists, adenophostins A(1) and B(2),
      were isolated from the culture broth of Penicillium brevicompactum SANK 11991 and
      SANK 12177. Its structures were related to adenine nucleotides. The agonistic
      activity of adenophostins A or B for binding to the InsP3 receptor was higher
      than InsP3 itself.

PMID- 8270486
TI  - Aquastatin A, an inhibitor of mammalian adenosine triphosphatases from Fusarium
      aquaeductuum. Taxonomy, fermentation, isolation, structure determination and
      biological properties.
AB  - A new inhibitor of mammalian adenosine triphosphatases, designated aquastatin A,
      has been isolated from a fungus identified as Fusarium aquaeductuum. The
      structure of this compound has been determined by MS and NMR analyses. It
      inhibits Na+/K(+)-ATPase with an IC50 value of 7.1 microM, and H+/K(+)-ATPase
      with an apparent IC50 value of 6.2 microM.

PMID- 8270487
TI  - IC101, extracellular matrix antagonist produced by Streptomyces sp. MJ202-72F3.
      Production, isolation, structure determination and biological activity.
AB  - In our search for inhibitors of cell adhesion to components of extracellular
      matrix (ECM), fibronectin, laminin and collagen type IV, we succeeded in finding
      a novel cyclic hexadepsipeptide antibiotic, named IC101, which was isolated from
      cultured mycelium of Streptomyces albulus MJ202-72F3. It was purified by
      centrifugal partition chromatography, preparative reverse phase HPLC and Sephadex
      LH-20 and was obtained as a white powder. IC101 strongly inhibited cell adhesion
      to ECM components, suppressed immune responses in vitro and in vivo, and
      exhibited antimicrobial activity on Gram-positive bacteria.

PMID- 8270488
TI  - Novel cytocidal compounds, oxopropalines from Streptomyces sp. G324 producing
      lavendamycin. I. Taxonomy of the producing organism, fermentation, isolation and
      biological activities.
AB  - In the course of our investigation aimed at the discovery of novel antitumor
      antibiotics from microorganisms, Streptomyces sp. G324 was found to produce the
      antitumor antibiotic, lavendamycin, and also, to yield the novel beta-carboline
      compounds, oxopropalines. We isolated five compounds as oxopropalines A, B, D, E
      and G. Oxopropalines B, D and G showed cytocidal activities against human or
      murine tumor cell lines in vitro.

PMID- 8270489
TI  - Novel cytocidal compounds, oxopropalines from Streptomyces sp. G324 producing
      lavendamycin. II. Physico-chemical properties and structure elucidations.
AB  - Novel cytocidal compounds designated oxopropalines A, B, D, E and G were isolated
      from the fermentation of an actinomycete named Streptomyces sp. G324, a strain
      that also produced an antitumor antibiotic, lavendamycin. All these compounds
      possessed a beta-carboline chromophore. The structures of the oxopropalines were
      elucidated by several NMR spectral analyses and other spectroscopic experiments.

PMID- 8270490
TI  - T cell activation by conagenin in mice.
AB  - Conagenin (CNG), a low molecular immunomodulator, enhanced incorporation of
      [3H]thymidine into T cells activated by concanavalin A but did not to non
      activated T cells. The culture supernatants of activated T cells treated with CNG
      enhanced incorporation of [3H]thymidine into cytokine dependent cell lines, CTLL
      2 and IC-2 cells. This indicates that CNG exclusively acts on activated T cells
      and stimulates them to promote DNA synthesis and to produce lymphokines, which
      may include T cell growth factors and hematopoietic growth factors. These
      activities were also observed with T cells taken from mice given CNG.

PMID- 8270491
TI  - Effect of conagenin in tumor bearing mice. Antitumor activity, generation of
      effector cells and cytokine production.
AB  - Antitumor effects and function of T cells in tumor bearing mice given conagenin
      (CNG), a low molecular immunomodulator, were investigated. The administration of
      CNG, once a week for 4 weeks, was the most effective schedule in inhibiting
      growth of IMC carcinoma, a syngeneic tumor. In this regimen, cytotoxic T
      lymphocytes and natural killer activities in spleens of CNG treated mice were
      maintained at higher levels than those of non-treated mice. Lymphokine production
      by splenic T cells was also enhanced in cultures, whereas monokine production by
      macrophages, which was increased in accordance with tumor growth, was reduced by
      CNG administration. The antitumor effect of CNG was not observed in mice given
      anti-asialo GM1 serum and in athymic mice. Results shown in this report suggest
      that CNG exerts its antitumor effects through activation of T cells and
      enhancement of generation of antitumor effector cells.

PMID- 8270492
TI  - WS1279, a novel lipopeptide isolated from Streptomyces willmorei. Biological
      activities.
AB  - WS1279, a new lipopeptide isolated from the fermentation broth of Streptomyces
      willmorei No. 1279, stimulated the proliferation of mouse bone marrow cells in
      vitro and accelerated the recovery of granulocyte counts in bone marrow from
      leukopenia induced by mitomycin C (MMC) in mice. The glycerylcysteine moiety of
      WS1279 is necessary and the lipid peptide structure is required for manifestation
      of full stimulating activity in vitro. WS1279 was the most effective on the
      proliferation of bone marrow cells among the tested immunostimulants in vitro.
      However, the effect of WS1279 on restoration of reduced granulocyte counts in MMC
      induced leukopenia in mice was less than that of FK-565, lipopolysaccharide,
      picibanil or forphenicinol. WS1279 augmented host resistance to infection with
      Staphylococcus aureus 47 in normal and immunosuppressed mice.

PMID- 8270493
TI  - Affinity of E1077, a new cephalosporin, for penicillin-binding proteins of
      Staphylococcus aureus and its antistaphylococcal activity.
AB  - Potent antistaphylococcal activity was conferred on E1077 by the introduction of
      the propenylammonium group at the 3-position in the cephem nucleus and of the
      fluoromethoxyimino group in the 7 beta-side chain. Antistaphylococcal activity
      was more markedly increased by the former group than by the latter. This effect
      seemed likely to be due to the increased high affinity for penicillin-binding
      protein (PBP) 3, which may be one of the essential PBPs of Staphylococcus aureus,
      and secondly for PBP 4. E1077 also showed more potent bactericidal activity than
      did cefpirome at concentrations above the MICs, although the MICs of E1077 for S.
      aureus were only half those of cefpirome. While cefpirome showed little killing
      activity within 4 hours at its MIC, the addition of cefoxitin (0.05
      micrograms/ml), a specific inhibitor for PBP 4, enhanced the killing activity of
      cefpirome to match that of E1077. In addition, peptidoglycan (PG) obtained from
      cells grown with the subinhibitory E1077 concentration was more susceptible to
      lytic enzymes than that from untreated cells or cefpirome-treated cells. These
      results indicated that the increased inhibition of PBPs 3 and 4 by E1077, which
      was brought about by the introduction of two distinctive functional groups, led
      to the enhanced antistaphylococcal activity and to the production of poorly cross
      linked PG, and thereby to rapid bactericidal activity.

PMID- 8270494
TI  - Dephostatin, a novel protein tyrosine phosphatase inhibitor produced by
      Streptomyces. II. Structure determination.
AB  - Dephostatin, a novel tyrosine phosphatase inhibitor, was isolated from the
      culture broth of Streptomyces sp. MJ742-NF5. The structure was elucidated to be 2
      (N-methyl-N-nitroso)hydroquinone by spectral and chemical analyses of dephostatin
      and its derivatives.

PMID- 8270495
TI  - Synthesis and antitumor activity of anthracycline disaccharide glycosides
      containing daunosamine.
AB  - Daunosamine, as its 4-O-acetyl-3-N-trifluoroacetyl glycosyl chloride derivative
      (1b), has been coupled alpha-L-glycosidically to the 3- and 4-mono-O-acetyl
      derivatives of L-rhamnal to afford disaccharide glycal derivatives, whose
      conversion into the corresponding 2-deoxyglycosides by sequential
      alkoxyiodination-tributylstannane reduction has been evaluated. The sequence
      successfully demonstrated with the methyl glycosides was successfully extended
      with daunomycinone as the aglycon, providing a preparative route to 7-O-[3-O-(3
      amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)- 2,6-dideoxy-alpha-L-arabino
      hexopyranosyl]daunomycinone hydrochloride (15), an analogue of natural
      anthracycline antibiotics containing daunosamine and a 2,6-dideoxy-L-hexose.

PMID- 8270497
TI  - Synthesis and antibacterial activity of new 2-substituted penems. I.
AB  - A new type of penem derivative (3-6) having a cyclic amidine moiety or a
      quaternary heterocycle moiety at the C-2 position was prepared. The
      susceptibility to renal dehydropeptidase-1 (DHP-1) and the antimicrobial activity
      of these compounds were determined. Some of these compounds (5,6) showed a broad
      spectrum of antibacterial activity, including activity against Pseudomonas
      aeruginosa.

PMID- 8270496
TI  - Synthesis and biological activity of derivatives of glycopeptide antibiotics
      eremomycin and vancomycin nitrosated, acylated or carbamoylated at the N
      terminal.
AB  - Nitrosation, carbamoylation or acylation of the glycopeptide antibiotics
      eremomycin or vancomycin produced series of derivatives substituted at the N
      terminus of the peptides. Though the modified amino group in these derivatives is
      not capable of protonation, N-nitroso derivatives retain antibacterial activity
      in vitro and in vivo. N-Carbamoyleremomycin has low activity, and N-Cbz
      eremomycin and N-Boc-eremomycin are devoid of antibacterial activity, both in
      vitro and in vivo.

PMID- 8270498
TI  - Thiangazole, a new thiazoline antibiotic from Polyangium sp. (myxobacteria):
      production, antimicrobial activity and mechanism of action.

PMID- 8270499
TI  - Isolation of RP 71955, a new anti-HIV-1 peptide secondary metabolite.

PMID- 8270500
TI  - Anthracycline metabolites from baumycin-producing Streptomyces sp. D788. III. New
      anthracycline metabolites produced by blocked mutants 4L-660 and YDK-18.

PMID- 8270501
TI  - Griseulin, a new nitro-containing bioactive metabolite produced by Streptomyces
      spp.

PMID- 8270502
TI  - An assay for the detection of bacterial DNA gyrase inhibitors.
AB  - In summary, we have developed a sensitive detection system for inhibitors of
      bacterial DNA gyrase. The use of B. subtilis as the host organism confers the
      advantage that it is sensitive to both gyrase subunit A and B inhibitors, whereas
      E. coli is relatively insensitive to B subunit inhibitors in vivo. Using this
      assay, we identified a new DNA gyrase inhibitor with a novel structure.

PMID- 8270503
TI  - Diverse effects of indolocarbazole compounds on the cell cycle progression of ras
      transformed rat fibroblast cells.

PMID- 8270504
TI  - Azicemicin A, a new antimicrobial antibiotic from Amycolatopsis.

PMID- 8270505
TI  - Comparison of digestibility, nutritive value, and storage characteristics of
      different forms of cottonseed in diets fed to lactating dairy cows.
AB  - Thirty-two Holstein cows averaging 70 d postpartum were used to compare
      digestibility of whole short staple cottonseed (SS) to whole Pima (WP), coarsely
      cracked Pima (CrP), and ground Pima (GP) cottonseeds and their effects on
      lactational performance. Cottonseed was fed at 15% of diet DM. Milk and solids
      corrected milk (SCM) yields were higher for cows fed GP than for cows fed CrP or
      WP but were not different from yields of cows fed SS. Feed efficiency (SCM/DMI)
      was higher for cows fed GP and SS than for those fed WP. Milk of cows fed GP was
      lower in stearic acid but higher in linoleic and linolenic acids than milk of
      cows fed SS. Whole seeds passing into the feces (percentage of consumed) were
      higher for WP (12.3%) than for SS (6.2%). Total tract digestibility of ether
      extract was lower for WP than for other diets. Digestibilities of other nutrients
      were not different. To test storage characteristics, samples of cottonseed were
      incubated at 32 degrees C and 30% relative humidity for 0, 10, 20, and 30 d, or
      stored at ambient temperatures in covered buckets for 9 mo. No differences in
      amount of free fatty acids between incubated samples were noted, and only CrP
      stored in buckets for 9 mo was significantly higher in free fatty acids than
      initial or frozen seed. No differences in aflatoxin were detected, and levels
      were very low. Milk yield of cows fed GP diets was similar to that of cows fed SS
      diets and slightly higher than those of cows fed CrP or WP diets. Processing the
      Pima seed increased feed efficiency.

PMID- 8270506
TI  - The effects of ruminally undegradable protein, propionic acid, and monensin on
      puberty and pregnancy in beef heifers.
AB  - Two hundred ten spring-born English crossbred beef heifers were used in two
      experiments in consecutive years using a randomized complete block design. The
      objectives were to determine the effects of increasing dietary intake of
      ruminally undegradable protein or propionic acid on the occurrence of puberty and
      to elucidate the mechanism by which monensin decreases age of puberty in beef
      heifers. Diets were fed for 120 d beginning in mid-November and consisted of
      mature grass hay and barley straw with .45 kg.animal-1 x d-1 supplement (CON)
      formulated to obtain .4 kg.animal-1 x d-1 of BW gain; .5 kg of supplement similar
      to CON and containing an additional 250 g of ruminally undegradable intake
      protein supplied from blood and corn gluten meal (UIP); .45 kg of supplement
      similar to CON composition and containing 400 g.animal-1 x d-1 of a 50% water and
      50% propionic acid mixture (PROP); or .45 kg of supplement similar to CON
      supplying 200 mg.animal-1 x d-1 of monensin (MON). The hay:straw ratio in each
      diet was adjusted biweekly, to maintain similar BW gains for heifers fed each
      dietary treatment. As planned, BW gains were similar (P > .1) for all heifers.
      The heifers fed MON were 21 d younger (P < .05) at first estrus than heifers fed
      UIP; CON and PROP were intermediate and similar to heifers fed MON and UIP. The
      heifers fed UIP were 7 to 8 kg heavier (P < .05) at puberty than CON- or PROP
      treated heifers. The heifers fed PROP were 6 kg heavier (P < .1) at puberty than
      heifers fed MON. Heifers that received UIP required less (P < .05) TDN than did
      heifers that received CON or PROP to achieve similar gain. Pregnancy rate was
      similar for all treatment groups. Feeding UIP in excess of NRC CP requirements
      may improve energy utilization of heifers fed mature roughages but may delay the
      onset of puberty compared with heifers fed monensin. This study demonstrated that
      nutrient composition of the diet may influence age of puberty independent of
      growth rate.

PMID- 8270507
TI  - Feedlot performance, carcass characteristics, hormones, and metabolites in steers
      actively immunized against growth hormone-releasing factor.
AB  - Large-framed Simmental and Charolais steers were actively immunized against
      growth hormone-releasing factor (GRF) to evaluate the effect on growth, carcass
      characteristics (especially intramuscular fat deposition), and concentrations of
      somatotropin (ST) and IGF-I. Primary immunizations of 1.5 mg of GRF-(1-29)-Gly
      Gly-Cys-NH2 conjugated to 1.5 mg of human serum albumin (GRFi, n = 12) or 1.5 mg
      of human serum albumin (HSAi, n = 12) were given at approximately 10 mo of age.
      Booster immunizations of .5 mg of the appropriate antigen were given at d 49 and
      125. Weights of steers administered GRFi were less (P < .05) than those given
      HSAi at 126 d (34.6 kg) or at 262 d (48.2 kg) after treatment. Carcass weights
      were 28.2 kg less (P < .01) for GRFi than for HSAi steers. Dry matter intake was
      not affected by immunization treatment, whereas feed efficiency was reduced in
      GRFi steers. Marbling scores were higher (P < .05) for HSAi than for GRFi steers
      but similar percentages (83.3) of both treatments graded Low Choice or higher.
      Rib sections of GRFi steers contained more fat (31.2 vs 25.0%) and less lean
      (63.3 vs 68.4%) than those of HSAi steers (P < .05). A breed x treatment
      interaction was observed for percentage of fat within the trimmed longissimus
      muscle (P < .05); percentage of fat was similar for Charolais and Simmental
      steers when immunized against HSAi but was higher for Simmental than for
      Charolais when immunized against GRFi.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270508
TI  - Evaluating two sources of dried whey and the effects of replacing the corn and
      dried whey component with corn gluten meal and lactose in the diets of weanling
      swine.
AB  - Three experiments were conducted to evaluate the efficacy of replacing corn and
      dried whey with corn gluten meal (CGM) and lactose, and to evaluate two sources
      of edible-grade dried whey that elicited different postweaning pig growth
      performances. In Exp. 1, two corn-soybean meal (C-SBM) diets without or with 20%
      dried whey (C-SBM-DW) were formulated to contain 1.15% lysine. A third diet
      replaced the corn and dried whey component with CGM and lactose. The experiment
      used 108 crossbred pigs weaned at 23 +/- 2 d of age weighing 6.25 kg BW and was
      conducted in six replicates as a randomized complete block design. Pig weight
      gains when the C-SBM-DW diet was fed were poor in one trial, whereas a second
      trial resulted in improved (P < .01) performance responses to the inclusion of
      dried whey. The CGM-SBM-lactose diet resulted in pig gains that equaled the
      performance responses of the C-SBM-DW diet of Trial 2. A second experiment was
      subsequently designed to evaluate the effects of adding lactose or lactalbumin to
      the CGM-SBM-DW diets using the two dried whey sources that had been identified as
      good or poor quality in Exp. 1. Diets included dried whey at a 25% level and were
      formulated to a low lysine level (.95%) to assess the nutritional efficacy of the
      dried whey sources.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270509
TI  - Choice of optimality criteria for the design of crossbreeding experiments.
AB  - Crossbreeding experiments carried out over several generations and analyzed using
      genetic models including additive, dominance, and epistatic effects deserve
      careful planning. Designs should be optimized with respect to the specific aim of
      the experiment. Using an experiment with guinea pigs as an example, designs were
      optimized for three different criteria: D-optimality, where the determinant of
      the variance-covariance matrix of all parameters in the genetic model is
      minimized, DS-optimality, where a specific subset of parameters is of special
      interest and the respective determinant is minimized, and DA-optimality, where a
      linear function or a set of linear functions of the parameters in the model is of
      interest. The linear function used in this particular case relates to the
      comparison of a composite line of two breeds and a rotational crossbreeding
      system at equilibrium. The designs produced by a sequential design algorithm
      depend very much on the optimality criterion. Designs that are optimal for the
      comparison of composites and rotations are very inefficient for the estimation of
      the whole set of parameters in the model or the specific subset of special
      interest in this case. Assuming that the underlying genetic model is correct,
      composites and rotations at equilibrium may be compared extremely efficiently
      using only crosses arising in the first three generations of crossbreeding.

PMID- 8270510
TI  - Contribution of breed, cow weight, and milk yield to the preweaning, feedlot, and
      carcass traits of calves in three beef breeding systems.
AB  - Data were obtained from 1980 to 1987 on animals belonging to one of three
      breeding systems: Hereford, small rotation, and large rotation. Differences among
      Angus-, Gelbvieh-, Pinzgauer-, and Tarentaise-sired calves within the small
      rotation system were generally not detected as significant for the preweaning
      traits of gestation length, calving ease, birth weight, gain to weaning, or creep
      feed intake with the exception of a longer gestation length for Gelbvieh-sired
      calves. Similarly, differences for feedlot gain, days on feed, feedlot intake,
      and the carcass characteristics of carcass weight and marbling, and lean, fat,
      and bone percentages were generally nonsignificant. Gelbvieh- and Pinzgauer-sired
      calves had higher growth rate, market weight, and longissimus muscle area than
      Angus- or Tarentaise-sired calves with a corresponding tendency for increased
      feed intake. Differences among Charolais-, Maine Anjou-, and Simmental-sired
      calves within the large rotation were not significant for any of the traits
      studied. Increased cow weight was positively associated with birth weight,
      significantly so for the small rotation. No patterns of association with cow
      weight were found for other preweaning traits. Increased milk yield was
      positively, but not always significantly, associated with gestation length and
      all weights and was negatively associated with creep intake. Neither cow weight
      nor milk yield showed any consistent association with feedlot or market traits,
      although increased milk yield was shown to be associated with higher daily gains
      for Hereford and small rotation and with higher carcass and market weights for
      Hereford. In general, associations of traits of calves with weight and milk yield
      of their dams were not detected as being different among breeding systems; except
      the effect of increased milk yield on gain to weaning was greater in Hereford
      than in large rotation cows.

PMID- 8270511
TI  - Integrated systems analysis of sow replacement rates in a hierarchical swine
      breeding structure.
AB  - Sow replacement rates in a three-tiered breeding structure were investigated for
      a 10-yr planning horizon using a stochastic life-cycle swine production model.
      Market hogs were produced in a three-breed static crossing program and marketed
      on a liveweight basis. Growth and reproductive traits of individual pigs were
      simulated using genetic, environmental, and economic parameters. Sows were culled
      after a maximum of 1, 5, or 10 parities. Systems were defined by maximum sow age
      at culling and included combinations of 1- and 5-parity nucleus and 1-, 5-, and
      10-parity multiplier and commercial tiers. Economic response to index selection
      was considerable for all culling alternatives with yearly increases in system
      profits ranging from $1.06 to 1.44 for each commercial hog marketed. When sows
      were culled after one parity in nucleus, multiplier, and commercial tiers,
      respectively (1,1,1), annual changes in net returns and all cost measures were 40
      to 50% larger than responses in systems with lower sow replacement rates. Based
      on 10-yr averages for net returns, systems with low multiplier- and commercial
      level replacement rates were more profitable than systems with higher replacement
      rates. The most profitable system (5,10,10) differed from the least profitable
      system (1,1,1) by more than $10 per pig, but when the (1,1,1) system was
      excluded, the range was only $3 per pig. The system with lowest replacement rates
      supported 3,388 more multiplier and 34,151 more commercial sows from a 750-sow
      nucleus level than the (1,1,1) system. Output from the two extremes differed by >
      664,000 commercial market hogs sold.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270512
TI  - Effect of selection for maternal and direct genetic effects on genetic
      improvement of litter size in swine.
AB  - Optimum weighting ratios of maternal:direct EBV for litter size using an animal
      model were examined to achieve maximum genetic improvement (direct plus maternal
      response). Stochastic simulation of a 120-sow herd over a 10-yr period of
      selection was used (20 replicates). Directional selection was based on a merit
      function of maternal and direct EBV for first-parity litter size. Optimum
      weighting ratios for maternal to direct EBV in pure- and crossbreeding schemes
      with different genetic correlations between maternal and direct effects were
      obtained. Genetic gain in maternal and direct effects was more sensitive to
      change in weighting ratios of maternal to direct estimates of breeding values
      under an animal model than earlier theoretical studies showed for selection
      index. In the purebreeding scheme, the weighting ratios of maternal:direct
      effects of 1:1, 1.25:1, and -.5:1 resulted in the highest overall response of
      3.11, 1.73, and .69 pigs after 10 yr of selection with genetic correlations
      between maternal and direct effects of 0, -.5, and -.9, respectively. In the
      crossbreeding scheme with a male dam line selected for direct effects only and a
      female dam line selected for an optimum weighting ratio of maternal and direct
      effects the overall response was always higher with 3.19, 1.89, and 1.31 pigs/10
      yr for the genetic correlations 0, -.5, and -.9, respectively, than in the
      purebreeding scheme. With a large negative correlation between maternal and
      direct effects a meaningful overall response of litter size was achieved only in
      the crossbreeding scheme. The effect of negative weighting of maternal effects to
      increase direct response with a large negative correlation between maternal and
      direct effects was also examined as well as the influence of weighting ratios on
      accuracy of evaluation, additive genetic variance, prediction error variance, and
      correlation between maternal and direct EBV.

PMID- 8270513
TI  - Restricted maximum likelihood estimation of variance components from field data
      for number of pigs born alive.
AB  - Variance components for number of pigs born alive (NBA) were estimated from sow
      productivity field records collected by purebred breed associations. Data sets
      analyzed were as follows: Hampshire (n = 13,537), Landrace (n = 10,822), and
      Spotted (n = 3,949). Variance components for service sire, sire of sow, dam of
      sow, and residual effects on NBA (adjusted for parity) were estimated. The single
      trait model included relationships between service sires, sires of sows, and dams
      of sows. The model was implemented using an expectation maximization (EM) REML
      algorithm. A sparse-matrix solver was also used. Heritability estimates for NBA
      were .13, .13, and .12 for Hampshire, Spotted, and Landrace, respectively.
      Estimates of maternal genetic (co)variances (m2) expressed as a proportion of the
      phenotypic variance were .05, .01, and .03 for Hampshire, Spotted, and Landrace,
      respectively. Results indicated that service sires account for 1 to 2% of the
      total variation for NBA. Genetic effects influencing NBA seem to be small in
      these data sets, but selection for increased NBA should be effective.

PMID- 8270514
TI  - Comparison of Finnish Landrace and Romanov as prolific breeds in a terminal-sire
      crossbreeding system.
AB  - Targhee ewes lambing to Romanov vs Finnish Landrace rams gave birth to .22 more
      lambs (P = .02) and had .15 more lambs alive at weaning (P = .11) but did not
      rear more lambs. Finnish Landrace x Targhee (FT) and Romanov x Targhee (RT) lambs
      were similar for preweaning survival and for all growth and carcass traits
      studied. Romanov x Targhee ewes were 14.2 +/- 6.2 d younger (P = .02) at their
      first estrus and 12.1 +/- 2.8 d younger (P < .01) at their first lambing than FT
      ewes. The ovulation rate of RT ewes exceeded that of FT ewes by .35 (P < .01).
      Romanov x Targhee ewes gave birth to .42 more (P < .01) lambs per ewe lambing,
      had .39 more (P < .01) lambs alive at weaning per ewe lambing, and reared .15
      more (P = .03) lambs per ewe lambing than FT ewes. Embryonic survival, adjusted
      for ovulation rate, was greater (P < .01) for RT (88.3 +/- 3.3%) than for FT
      (80.0 +/- 3.7%) ewes. Lamb survival was similar for the two F1 crosses, with or
      without adjustment for number of lambs born. Overall survival (the proportion of
      ova that resulted in weaned lambs) was greater (P = .02) for RT ewes (77.6 +/-
      4.2%) than for FT ewes (67.5 +/- 4.7%), at the same ovulation rate. When ewes
      were credited with all the lambs they gave birth to, RT ewes produced 4.6 +/- 1.8
      kg more (P < .01) weight of lamb at weaning.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270515
TI  - Estimates of maturing rates and masses at maturity for body components of sheep.
AB  - Weight data for fleece-free empty body, carcass and offal components, and their
      chemical constituents (protein, water, lipid, and ash) were collected via serial
      slaughter techniques. Rams sired by a sheep breed of high genetic merit for
      growth were slaughtered from birth through 48 mo of age. Approximately six rams
      were killed at each of 13 slaughter ages. The data were fit with a nonlinear
      function Yt = A(1-Be-kt) to provide estimates of rates of maturing (k) and weight
      at maturity (A) for components of interest. Except for the testes, all tissues
      met the convergence criterion. The proportion of offal components relative to
      empty BW was greatest at birth and steadily declined after this time. Rates of
      maturing for visceral organs (except for the heart) and the protein constituent
      of the offal were of greater magnitude than the carcass and nonprotein
      constituents of both the offal and carcass. Estimated maturing rate and weight at
      maturity for lipid of the carcass exceeded corresponding estimates of the offal
      lipid. Evidence was provided suggesting that the developmental patterns of body
      components may be established by functional demand.

PMID- 8270516
TI  - Pork quality and the expression of stress protein Hsp 70 in swine.
AB  - The expression of heat shock protein with a molecular weight of 70 kDa (Hsp 70)
      in porcine tissue and its potential relationship to stress susceptibility was
      studied. Twelve pigs, four of each genotype (NN, Nn, and nn) for halothane
      sensitivity were slaughtered. At 45 min postmortem, several tissues (liver,
      kidney, spleen, skeletal and cardiac muscle, and adrenal gland) were sampled for
      Hsp 70 analysis. At 24 h postmortem, longissimus and semimembranosus muscle were
      sampled for assessment of meat quality. Water-holding and water-binding capacity,
      color, and protein denaturation of samples from halothane-positive animals
      indicated that these animals had been stressed. Homozygous nn pigs demonstrated a
      lower pH45 and higher L-value at 48 h than their NN and Nn counterparts (P <
      .05). The longissimus, but not semimembranosus, muscle of nn pigs demonstrated
      lower water-holding capacity and greater protein denaturation than that of NN or
      Nn pigs (P < .05). The water-binding capacity of both longissimus and
      semimembranosus was less in nn than in Nn or NN pork (P < .05). Using one
      dimensional PAGE and Western blotting, Hsp 70 was shown to be present in all
      tissues examined. With two-dimensional PAGE followed by blotting, the presence of
      the cognate and inducible form of Hsp 70 was investigated. There did not seem to
      be a relationship between stress (based on meat quality) and expression of either
      form of Hsp 70.

PMID- 8270517
TI  - Effects of postmortem injection time, injection level, and concentration of
      calcium chloride on beef quality traits.
AB  - Two experiments were conducted to determine the optimum protocol for maximizing
      meat quality with CaCl2 injection. Experiment 1 compared the effects of 30 min or
      24 h postmortem injection of 175 mM CaCl2 or water at 10% (wt/wt) to controls on
      various measures of meat quality. An injection of CaCl2 reduced (P < .05) shear
      force values in all three beef muscles evaluated (longissimus, semimembranosus,
      and triceps brachii). Retail lean color was not affected (P > .05) by a CaCl2
      injection at 24 h postmortem, but was slightly darker (P < .05) for an injection
      at 30 min postmortem. Psychrophilic and total aerobic microbial counts were
      higher (P < .05) in 30-min than in 24-h treatments and were higher (P < .05) in
      CaCl2- or water-injected semimembranosus muscle than in the control, but the
      treatment differences were minimal in 24-h injected meat. Experiment 2 compared
      the effects of 24-h postmortem injection of 200 mM or 250 mM CaCl2 at either 5 or
      10% (wt/wt) to controls on meat quality traits. Both 200 and 250 mM CaCl2 reduced
      (P < .05) shear force values compared with the control. In addition, variation in
      shear force was decreased (P < .05) with CaCl2 injection. Beef flavor intensity
      was slightly lower (P < .05) and off-flavor ratings were slightly higher (P <
      .05) in CaCl2-injected meat, but the small differences were of no practical
      significance. Retail lean color was not affected (P > .05) by injection of the
      CaCl2 at 24 h. Injecting 200 mM CaCl2 at 5% (wt/wt) into 24 h postmortem meat can
      produce consistently tender meat without compromising other palatability or lean
      quality traits.

PMID- 8270518
TI  - Effects of feeder cattle frame size, muscle thickness, and age class on days fed,
      weight, and carcass composition.
AB  - Feeder steers (n = 189) representing nine frame size x muscle thickness
      subclasses were started on a high-concentrate diet as calves, yearlings, or long
      yearlings and slaughtered at a constant s.c. fat thickness (13.5 mm) to determine
      the effects of feeder cattle frame size (large, medium, small), muscle thickness
      (No. 1, No. 2, No. 3), and age class on carcass traits and composition. After
      slaughter, one side of each carcass was physically separated into muscle, fat,
      and bone. Subcutaneous, intermuscular, and internal fat depot percentages were
      calculated as proportions of total fat weight. Effects of age class, frame size,
      and muscle thickness were significant for time-on-feed, slaughter weight, and
      carcass weight. Among age classes, long yearling steers required the fewest (P <
      .05) days on feed and heaviest (P < .05) live weights to reach the fat thickness
      end point. Increased frame size and decreased muscle thickness were associated
      with greater time-on-feed and heavier weights at slaughter. However, the effects
      of muscle thickness on slaughter traits were not consistent among frame and age
      subclasses; effects were greatest among large-framed steers and smallest among
      long yearling steers. Compositional differences (P < .05) were noted among age
      and muscle subclasses. Long yearling steers had the lowest (P < .05) percentage
      of bone among all age classes and a higher (P < .05) percentage of fat than
      steers fed as calves. No. 2 steers had the highest (P < .05) percentage of bone
      and the lowest (P < .05) muscle:bone ratio among muscle thickness groups; no (P >
      .05) compositional differences were observed between No. 1 and No. 3 steers.
      Differences in muscle:bone ratio, though statistically significant, were
      relatively small in magnitude and were not directionally consistent with
      differences in muscle thickness. Differences in fat partitioning were noted among
      frame and muscle subclasses. Large-framed steers had the lowest (P < .05)
      percentage of s.c. fat and the highest (P < .05) percentage of internal fat among
      frame sizes. No. 3 steers deposited the lowest (P < .05) percentage of
      intermuscular fat and the highest (P < .05) percentage of internal fat.

PMID- 8270519
TI  - The effects of porcine somatotropin and dietary lysine on growth performance and
      carcass characteristics of finishing swine fed to 105 or 127 kilograms.
AB  - One hundred twenty barrows (initially 59 kg) were used to determine the effects
      of dietary lysine and porcine somatotropin (pST) on growth performance and
      carcass characteristics of finishing pigs fed to heavy market weights (127 kg).
      Pigs were injected daily with either 4 mg of pST or a placebo and fed diets
      containing either .8, 1.0, 1.2, or 1.4% lysine in a 2 x 4 factorial arrangement.
      Performance data were collected and evaluated for the weight ranges: 59 to 105,
      105 to 127, and 59 to 127 kg. In addition, daily accretion rates of protein
      (DPA), lipid (DLA), moisture, and ash were determined by slaughtering six
      randomly selected pigs at the start of the experiment, then one pig per pen when
      pigs reached mean weights of 105 and 127 kg. Pigs injected with pST had greater
      (P < .05) ADG than control pigs at all weight ranges. Increased dietary lysine
      had no effect (P > .20) on ADG during the entire trial (59 to 127 kg). Although
      control pigs showed no increase in ADG with increasing lysine, ADG of pST-treated
      pigs tended to increase. This resulted in a pST x lysine interaction (P < .07)
      for ADG from 59 to 127 kg. Feed consumption decreased (P < .05) in pigs from 59
      to 105 kg and 59 to 127 kg with pST treatment and with increasing dietary lysine.
      Feed conversion (G/F) was improved (P < .01) by pST administration and a tendency
      for a pST x lysine interaction (P < .12) was observed. At 105 kg, average backfat
      thickness, kidney fat, longissimus muscle area, and DPA were unaffected by
      dietary lysine but were improved by pST treatment (P < .01). At a slaughter
      weight of 127 kg, average backfat thickness decreased and DPA increased (linear,
      P < .05) with increasing dietary lysine and pST treatment (P < .01). Longissimus
      muscle area was increased and DLA was decreased (P < .01) by injections of pST
      but both were unchanged by dietary lysine. These data indicate that growth
      performance and carcass characteristics at 105 and 127 kg were improved by daily
      administration of 4 mg of pST. At both slaughter weights, increasing dietary
      lysine resulted in increased carcass leanness (increased carcass protein and
      decreased carcass lipid). Although increasing lysine did not improve overall (59
      to 127 kg) ADG and feed efficiency, pST-treated pigs showed a greater response to
      increasing dietary lysine. The data indicate that pST-treated pigs (4 mg/d)
      require approximately 28 g/d of lysine.

PMID- 8270520
TI  - Long-term effects of feeding a high copper diet to sows during gestation and
      lactation.
AB  - An experiment was conducted to assess the long-term effects of feeding a high Cu
      diet to sows during gestation and lactation. Fifty-five gilts averaging 152 kg BW
      and 10.3 mo of age were allotted on d 47 after mating to diets consisting
      primarily of corn and soybean meal and containing 0 to 250 ppm of added Cu (as
      CuSO4.5H2O). Both diets contained 8.8 ppm of Cu from the trace mineral mix, and
      both contained antibiotics (55 mg/kg of chlortetracycline in the gestation diet,
      110 mg/kg each of neomycin and oxytetracycline in the lactation diet). Sows
      continued on their respective diets throughout gestation and lactation, until
      culled from the herd or until they farrowed their sixth litter. Feed intake
      averaged 1.90 kg/d during gestation and 4.82 kg/d during lactation. A total of 86
      and 81 litters were farrowed by control and Cu-treated sows, respectively. Seven
      control and eight treated sows completed six parities. Farrowing rate (no.
      farrowed/no. bred) was less (P < .05) in gilts fed high Cu, but culling rate was
      reduced (P < .01) in sows receiving the high Cu diet. Sows fed high Cu diets were
      heavier in BW on d 108 of gestation before their second (P < .05) and third to
      fifth litters (P < .01) than controls. Sows fed high Cu diets farrowed larger
      litters of pigs (P < .10) and the pigs were 9% heavier at birth (P < .001) and 6%
      heavier at weaning (P < .01) than pigs from control sows.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8270521
TI  - Effect of calcium source, dietary calcium concentration, and gestation phase on
      various bone characteristics in gestating gilts.
AB  - Sixty gravid crossbred gilts were allotted to a 2 x 3 x 2 factorial arrangement
      of treatments: two Ca sources (sun-cured alfalfa meal and CaCO3), three dietary
      concentrations of Ca (50, 75, and 100% of NRC requirements), and two phases of
      gestation (55 and 105 d). The objectives were to determine the effect of Ca
      source, dietary Ca concentration, and gestation phase on bone characteristics
      (bone breaking strength, bone ash percentage, bone density, and bone ash density
      in the rib, thoracic, and coccygeal bones), to correlate bone responses to
      determine relative bone activity, and to determine reliability of the coccygeal
      bones as indicators of Ca status in the body. At 55 d, rib strength and coccygeal
      ash content were lower (P < .01) than at 105 d of gestation. A gestation phase x
      Ca concentration (P < .05) interaction occurred. As Ca concentration increased,
      thoracic strength and rib ash responded quadratically during each gestation
      phase, for which at 55 d a minima and at 105 d a maxima was produced at 75% of
      NRC. A Ca source x Ca concentration (P < .05) interaction occurred. Gilts fed
      alfalfa had the lowest rib bone and ash density when fed 75% of NRC for Ca,
      whereas gilts fed CaCO3 were highest at this level of Ca compared with the other
      concentrations. Generally, all bones were positively correlated with respect to
      their response to dietary Ca concentration. Few negative correlations were
      observed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270522
TI  - Effects of adding medium-chain triglycerides to sow diets during late gestation
      and early lactation on litter performance.
AB  - This experiment was conducted to determine whether feeding medium-chain
      triglycerides (MCT) to sows during late gestation and early lactation would
      improve neonatal pig survival. Beginning on d 91 of gestation and continuing
      through d 7 of lactation, sows were fed isoenergetic (7,000 kcal of ME/d) and
      isonitrogenous (278 g of CP/d) amounts of either control (19% starch, 2% soybean
      oil), long-chain triglycerides (LCT, soybean oil, 12%), or MCT (10% MCT, 2%
      soybean oil) diets. Sows (n = 18, 19, and 17, respectively) were induced to
      farrow on d 112 of gestation. Litters were weighed at birth, before suckling, and
      on d 1, 3, 7, and 21 of lactation. There was no effect of treatment on average
      pig weight at any time and no difference in the number of live pigs at birth.
      Beginning on d 3 (P < .05) and continuing through weaning (d 21, P < .02)
      survival was improved in litters from sows fed MCT relative to litters from sows
      fed the control diet. Overall survival rates were 80, 81, and 90% in control,
      LCT, and MCT groups, respectively. The greatest improvement in survival was
      observed in pigs weighing < 900 g at birth. Survival of pigs in this weight range
      was 32, 53, and 68% in control, LCT, and MCT treatments, respectively. Although
      feeding MCT resulted in an increase in content of medium-chain fatty acids in
      milk, these accounted for < 5% of the fatty acids in milk and likely cannot
      account for the improved survival rate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270523
TI  - Growth and plasma zinc responses of young pigs fed pharmacologic levels of zinc.
AB  - Three trials were conducted to evaluate high levels of Zn addition from various
      Zn sources on growth performance and plasma Zn responses of 8-kg pigs. Zinc
      supplements were added to 20% CP starting diets (125 mg of Zn/kg) containing
      antibiotics. Trial 1 was done to evaluate plasma Zn responses of pigs fed three
      different feed-grade Zn sources: ZnO where supplemental Zn levels were 0, 250,
      500, 1,000, 3,000, and 5,000 mg/kg; ZnSO4 at 1,500 or 2,500 mg of Zn/kg; and a
      zinc-lysine complex (Zn-Lys) at 1,500 or 2,500 mg of Zn/kg. Plasma Zn
      concentration as a function of supplemental Zn intake was fitted to a broken-line
      for ZnO data and to simple linear models for ZnSO4 and Zn-Lys data. For ZnO,
      plasma Zn did not increase until concentrations > 1,000 mg Zn/kg were fed. Above
      this level, plasma Zn increased linearly (P < .01) for all three sources of Zn,
      although slopes of the ZnO and Zn-Lys response curves were 56% (P < .05) and
      110%, respectively, of the ZnSO4 slopes. In Trial 2, five diets were fed: basal,
      3,000 and 5,000 mg of Zn/kg from ZnO, and 3,000 and 5,000 mg of Zn/kg from ZnSO4.
      Daily gain and daily feed intake were increased (P < .05) by ZnO addition,
      regardless of level, whereas ZnSO4 addition increased these performance indices
      only at the 3,000 mg of Zn/kg level of supplementation. Plasma Zn responses to
      ZnSO4 addition were almost double those of ZnO addition.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8270524
TI  - Differences between progeny of beef sires in susceptibility to fescue toxicosis.
AB  - Fifteen progeny of two Polled Hereford sires were fed endophyte-infected tall
      fescue seed (E+) to investigate variability in susceptibility to fescue
      toxicosis. One sire, bred in Missouri, was reputed to produce calves that were
      resistant to fescue toxicosis. The Control sire, from Virginia, had unknown merit
      for susceptibility. There were two phases in which E+ was included in the diet (2
      and 4) and three in which it was not (1, 3, and 5). Voluntary feed intake, serum
      prolactin, cholesterol, and alkaline phosphatase concentrations; ability to
      maintain homeothermy (afternoon minus morning rectal temperature); and heat
      transfer inefficiency (afternoon rectal minus afternoon surface temperatures)
      were monitored. Intake and prolactin concentration were decreased by E+, but sire
      groups did not differ in responses across phases. Cholesterol levels were lower
      during E+ phases, and the rate of increase in cholesterol concentration after
      withdrawal of E+ differed between groups. Alkaline phosphatase concentrations
      were lower during E+ phases; calves from the Control sire showed greater
      reduction than calves sired by the Missouri sire. Ability to maintain homeothermy
      was reduced by E+, but the reduction did not differ between sire groups. Heat
      transfer inefficiences were not indicative of fescue toxicosis in this study.
      Evidence was not compelling to support the existence of differences between the
      sire groups for susceptibility to toxicosis. However, progeny of the Missouri
      bull had higher feed intake and lower rectal and body surface temperatures
      through nearly all phases of the trial. This may account for the reputation of
      the Missouri bull to sire calves with relatively high resistance to fescue
      toxicosis.

PMID- 8270525
TI  - Changes in serum somatotropin, somatotropin mRNA, and serum and follicular
      insulin-like growth factor-I in response to feed restriction in cows actively
      immunized against growth hormone-releasing factor.
AB  - Cyclic cows immunized against growth hormone-releasing factor (GRFi, n = 19),
      human serum albumin (HSAi, n = 10), or not immunized (CON, n = 18) were used to
      investigate the effects of feed restriction on serum and pituitary somatotropin
      (ST), pituitary ST mRNA, and serum and follicular IGF-I. Cows were either fed 2.7
      kg/d cottonseed hulls (R) or given ad libitum access to feed (AL) for 15 d.
      Ovaries bearing the largest follicle and pituitaries were collected on d 14, at
      44 to 45 h after injection of prostaglandin F2 alpha. Data from CON and HSAi cows
      were similar; thus, data were combined (represented as CON). Serum ST
      (nanograms/milliliter) on d 13 was greater (P < .09) in CON-R (5.3) than in CON
      AL (3.9), whereas ST in GRFi-AL (1.1) and GRFi-R (1.1; pooled SE = .4) were
      similar. Hemipituitary weight (grams) and ST mRNA (arbitrary units) were greater
      (P < .05) in CON (1.5 +/- .1 and 135 +/- 25) than in GRFi (1.0 +/- .1 and 90 +/-
      18) cows. Across immunization, ST mRNA and pituitary ST concentration (mg/100 mg
      of tissue), respectively, were greater (P < .06) in R (152 +/- 22 and 22.5 +/-
      1.9) than in AL (73 +/- 16 and 17.3 +/- 1.8) cows. Immunization and diet
      decreased (P < .05) serum IGF-I (nanograms/milliliter) on d 13 (CON, 176 +/- 7 vs
      GRFi, 42 +/- 8; AL, 120 +/- 7 vs R, 98 +/- 8). Concentrations of IGF-I in
      follicular fluid (FFL) from the largest follicle were lower in GRFi (29 +/- 3)
      than in CON (102 +/- 6) cows; however, IGF-I in FFL was similar in AL (70 +/- 9)
      and R (71 +/- 10) cows. In conclusion, GRFi decreased serum ST and IGF-I, and
      decreased ST mRNA. Feed restriction increased serum ST and ST mRNA, and decreased
      serum IGF-I. Although feed restriction and GRFi decreased serum IGF-I,
      concentrations of IGF-I in FFL were decreased only by GRFi.

PMID- 8270526
TI  - Relationships between reticular contractions and digesta passage in steers
      consuming alfalfa hay and barley straw combinations ad libitum.
AB  - A Latin square design experiment was conducted to determine changes in voluntary
      feed intake, passage of digesta from the ruminoreticulum, and changes in
      frequency, duration, and amplitude of reticular contractions in four Hereford
      crossbred steers (474 +/- 10 kg) fed diets consisting of different combinations
      of alfalfa hay and barley straw. Diets consisted of 1) 100% straw, 2) 67% straw
      and 33% hay, 3) 33% straw and 67% hay, and 4) 100% hay. The diets were offered at
      110% of ad libitum intake. Intakes of DM, OM, and lignin decreased linearly (P =
      .009, .011, and .003, respectively) with increased dietary straw, whereas diet
      did not affect intakes of NDF. Daily flows of DM, cell-wall components, and total
      contents at the duodenum decreased linearly with increased percentage of straw in
      the diet. Total digesta and fluid in the rumen increased linearly (P = .03 and
      .02) with increased straw content in the diet. Diet did not affect mean
      characteristics of reticular contractions. However, flow of total digesta through
      the proximal duodenum per contraction, per minute, and per centimeter of Hg
      amplitude of contraction decreased linearly (P = .01 and .02), whereas flow per
      centimeter of Hg tended to decrease (P = .08) with increased percentage of straw
      in the diet. Similarly, the flow of NDF through the proximal duodenum per
      reticular contraction and per minute of contraction decreased linearly (P = .006
      and .03) as the percentage of straw increased in the diet. However, when
      confounding effects of DMI were removed, the characteristics of reticular
      contractions were not related to DM and NDF flow at the duodenum.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8270527
TI  - Effects of dietary gossypol consumption on metabolic homeostasis and reproductive
      endocrine function in beef heifers and cows.
AB  - Our objectives were to determine the effects of incremental increases in dietary
      gossypol on metabolic homeostasis and reproductive endocrine function in
      postpubertal beef heifers and the long-term effects of elevated dietary gossypol
      on various metabolic and reproductive endocrine characteristics in mature cows.
      In Exp. 1, heifers (n = 6/group) were fed either 0, .5, 2.5, 5, 10, or 20
      g.animal-1 x d-1 of dietary free gossypol for 62 d. Erythrocyte membrane osmotic
      fragility was increased (P < .0001) in both the 10- and 20-g groups. Slight
      alterations in plasma concentrations of sorbitol dehydrogenase and K+ were also
      detected in the latter group. Treatment did not affect ADG, body condition
      scores, or concentrations of progesterone during the estrous cycle; however, mean
      concentrations of LH were higher (P < .001) in heifers fed 20 g/d of gossypol
      than in heifers in all other groups. In Exp. 2, lactating cows (n = 17)
      exhibiting regular estrous cycles were fed a control (no gossypol, n = 8) or high
      gossypol (20 mg.kg BW-1 x d-1 free gossypol, n = 9) diet for 33 wk. Mean BW and
      body condition scores did not differ during the feeding period. Erythrocyte
      membrane fragility was greater (P < .05) in the high-gossypol than in the control
      group. Magnitude of the preovulatory LH surge, luteal phase concentrations of
      progesterone, follicular fluid concentrations of estradiol and progesterone, in
      vitro granulosa cell estradiol production, and 60-d pregnancy rates were similar
      between groups. The amounts of gossypol fed in these experiments are not likely
      to affect reproductive performance adversely in beef heifers or cows.

PMID- 8270528
TI  - Ovulation rate and embryonic survival in Chinese Meishan and white crossbred
      pigs.
AB  - Two component traits of litter size of pigs, ovulation rate and embryonic
      survival, were examined in Meishan and composite white crossbred gilts and sows.
      At puberty, an ovulation rate of 12.5 was similar for Meishan (118 +/- 3 d of
      age) and crossbred gilts (217 +/- 3 d of age). The number of corpora lutea (CL)
      increased (4.3 CL) markedly (P < .01) from puberty to the sixth estrous period
      (220 d of age) in Meishan gilts but increased (1.2 CL) slightly from puberty to
      the fourth estrous period in crossbred gilts. At 220 and 280 d of age, Meishan
      gilts had a greater (P < .01) number of CL than did crossbred gilts (220 d, 16.7
      +/- .5 vs 12.7 +/- .4; 280 d, 16.5 +/- .7 vs 13.9 +/- .6 CL). Ovulation rate was
      greater (P < .01) in Meishan than in crossbred sows examined at 417 (18.1 +/- 1.2
      vs 15.2 +/- .4 CL), 608 (20.1 +/- 1.3 vs 17.1 +/- .6 CL), and 735 d of age (24.6
      +/- .8 vs 16.6 +/- .8 CL). Early embryonic survival was not significantly
      different in this study for Meishan and crossbred gilts (73 vs 81% ,
      respectively). However, at 30 d of gestation embryo weight and length, placental
      weight, and allantoic fluid volume were less (P < .01) in Meishan than in
      crossbred gilts. The effect of small embryo size and reduced placenta weights and
      allantoic fluid volumes at d 30 of gestation on subsequent fetal survival and
      development (uterine capacity) is unknown but may be an enhancement to the
      prolificacy of Meishan pigs. This observation indicates the need for further
      study of fetal-maternal interactions after d 30 of gestation in both Meishan and
      European pigs because of potential breed differences in uterine and placental
      function.

PMID- 8270529
TI  - Influence of the corpus luteum of pregnancy on ovarian function in postpartum
      ewes.
AB  - This study was conducted to determine the effects of the corpus luteum (CL) of
      pregnancy and(or) the previously gravid uterine horn (g-UH) on the incidence and
      site of ovulation and the duration of luteal function in postpartum (PP) ewes.
      Ewes were laparotomized at d 60 to 80 of gestation and assigned to one of four
      groups: 1) single g-UH, CL left intact (SI, n = 35); 2) single g-UH, CL removed
      (SR, n = 30); 3) twin g-UH, CL on both ovaries left intact (TI, n = 21); and 4)
      twin g-UH, CL removed from one ovary (TR, n = 32). On d 20 PP, the number of
      follicles on each ovary was determined at laparoscopy, and ewes received (i.m.)
      750 IU of hCG. Ovarian structures were determined at laparoscopy on d 24 PP.
      Blood samples were collected daily from d 20 to 40 PP and assayed for
      progesterone. more follicles (P < .05) were observed at laparoscopy on d 20 PP in
      SI/TI than in SR/TR groups (8.4 vs 6.0, respectively; SE = .4). Overall, 52% of
      the ewes had visible CL 4 d after hCG, and 73% of the ewes had elevated levels of
      progesterone by 7 d after hCG. The number of g-UH (S vs T) or status of the CL (I
      vs R) did not affect these responses. For SR ewes with hCG-induced CL on a single
      ovary, the incidence of CL formation on the ovary adjacent to g-UH was less (P <
      .05) than that for SI ewes (0 vs 57, respectively). Removal of the CL from S
      ewes, but not from T ewes, reduced follicular development and ovulation in
      response to hCG. Perhaps there is a positive systemic effect of the CL of
      pregnancy on postpartum ovarian function in ewes.

PMID- 8270530
TI  - Influence of microbial colonization of feed particles on determination of
      nitrogen degradability by in situ incubation.
AB  - Stable 15N isotope was used to determine the extent of microbial colonization of
      in situ incubation residues and the influence of colonization on estimates of
      ruminal degradability of feed N. In an in vitro trial, 15N:total N ratio remained
      unchanged after the soluble (by water, saline, or buffer solution) fraction of
      plant N was removed, suggesting that 15N was uniformly distributed in the soluble
      and insoluble N fractions. In three in situ trials, corn grain, corn husks, and
      alfalfa hay labeled with 15N as an internal marker were incubated in Dacron bags
      in the rumen of two lactating Holstein cows for 3, 6, 12, 24, 36, and 48 h.
      Enrichment of 15N in samples decreased with increased time of incubation for all
      feeds. At 48 h of incubation, 31, 71, and 65% of the residual N was microbial N
      for corn grain, corn husks, and alfalfa hay, respectively. Bacterial cell DM, as
      a percentage of residual DM, increased in a quartic manner, suggesting that
      microbial colonization depended on substrate availability. For 24, 36, and 48 h
      incubation, bacterial DM, as a percentage of total residue, averaged 10.0 +/-
      1.0% for corn grain, 17.5 +/- 1.4% for corn husks, and 22.0 +/- .2% for alfalfa
      hay. Apparent degradability of N after 48 h of incubation was approximately 65%
      for corn grain and alfalfa hay and 19% for corn husks. When corrected for
      bacterial N, degradabilities of N in all feeds increased and the degradabilities
      for corn husks became similar to those for corn grain.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8270531
TI  - Effects of supplemental protein source on ruminal fermentation, protein
      degradation, and amino acid absorption in steers and on growth and feed
      efficiency in steers and heifers.
AB  - In Exp. 1, four Holstein steers with cannulas in the rumen, abomasum and terminal
      ileum were used to determine the effects of 1) soybean meal (SBM), 2) heated SBM
      (HSBM), 3) corn gluten meal (CGM), or 4) a combination of HSBM and CGM (COMBO) as
      protein supplements on ruminal and total tract nutrient digestibilities and
      intestinal amino acid flows and absorption. In Exp. 2, 24 Holstein steers and 16
      Holstein heifers were used in a 56-d growth trial to study the effects of these
      protein supplements on growth, feed efficiency, and apparent digestibility of DM,
      OM, CP, and fiber components. Increasing undegradable intake protein (UIP) in
      diets with HSBM, CGM, and COMBO decreased ruminal fluid ammonia N concentrations
      (P < .05) and ruminal DM and OM digestion (P < .05) and increased flow to the
      abomasum and absorption from the small intestine of CP (P < .05), total amino
      acids (P < .05), and total essential amino acids (P < .01). Increasing UIP
      increased bacterial and nonbacterial CP and amino acids flowing to the abomasum
      (P < .05). However, UIP supplementation did not affect DMI, ADG, or feed
      efficiency in steers or heifers (P < .05).

PMID- 8270532
TI  - Feed intake and digestibility by cattle consuming bermudagrass or orchardgrass
      hay supplemented with soybean hulls and(or) corn.
AB  - Effects of supplementing cattle consuming tropical or temperate grass with corn
      and (or) soybean hulls on feed intake and digestibility were determined. In Exp.
      1, eight Holstein steer calves (210 +/- 9.2 and 269 +/- 9.4 kg initial and final
      BW, respectively), in two simultaneous Latin squares, were given ad libitum
      access to bermudagrass (B) or orchardgrass (O) hay without supplementation or
      with (DM basis) .5% of BW of ground corn (C), .7% of BW of soybean hulls (H), or
      .25% of BW of corn plus .35% of BW of soybean hulls (CH). Total OM intake was
      greater (P < .05) with than without supplementation (5.05, 6.04, 5.95, 6.06,
      6.04, 6.81, 6.61, and 6.69 kg/d), and digestible OM intake was affected by forage
      source (P < .05), mixing of supplement types (CH versus the mean of C and H; P <
      .09), and the forage source x supplementation interaction (P < .09; 2.65, 3.40,
      3.33, 3.46, 3.71, 4.14, 3.98, and 4.30 kg/d for B, B-C, B-H, B-CH, O, O-C, O-H,
      and O-CH, respectively). Total tract NDF digestibility was greater (P < .05) for
      O than for B diets and for H than for C (56.4, 53.9, 58.1, 56.9, 68.5, 64.9,
      67.7, and 69.6% for B, B-C, B-H, B-CH, O, O-C, O-H, and O-CH, respectively). In
      Exp. 2, mature cannulated beef cattle (524 +/- 1.6 kg BW) were used in a design
      similar to Exp. 1 with comparable dietary supplement levels.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8270533
TI  - Determination of the ruminal escape value and duodenal amino acid flow of
      rapeseed meal.
AB  - A 4 x 4 Latin square metabolism trial was conducted to evaluate protein escape
      potential, duodenal amino acid (AA) flows, and ruminal digestion effects of
      rapeseed meal (RSM) when fed with non-endophyte-infected tall fescue (Festuca
      arundinacea) hay. Four Holstein steers (average BW = 400 +/- 6.5 kg), each
      equipped with ruminal and duodenal cannulas, were fed twice daily at 0700 and
      1900. Protein supplements compared with RSM, soybean meal (SBM), blood meal (BM),
      and a negative control based on urea (U). Diets were formulated to contain 14%
      CP. Rapeseed meal-supplemented steers had lower (P < .01) ruminal NDF and OM
      digestibilities than steers fed SBM. Based on in situ data, the lower NDF, DM,
      and OM digestibilities that occurred when RSM was fed than when SBM and BM were
      fed were possibly due to the reduced digestibility of the hulls in the RSM.
      Ruminal pH was not different (P > .05) among treatments. Blood meal
      supplementation decreased (P < .01) ruminal and total tract CP digestibilities
      compared to all other supplements. Ruminal liquid and particulate passage rates
      were not changed (P > .05) by supplement source. Urea supplementation resulted in
      the highest (P < .01) ruminal ammonia concentration, whereas BM supplementation
      resulted in the lowest ruminal ammonia concentration (P < .01). Blood meal
      resulted in greater (P < .01) dietary protein flow to the duodenum than the other
      treatments. However, microbial efficiencies, as well as microbial DM and protein
      flows to the duodenum were not different (P > .05) among treatments.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8270534
TI  - Feed intake, digestibility, and live weight gain by cattle consuming forage
      supplemented with rice bran and(or) corn.
AB  - Effects of supplementing cattle consuming forage with rice bran and(or) corn on
      feed intake, digestibility, and live weight gain were determined. Holstein steer
      calves (176 +/- 4.3 kg average trial BW), in two simultaneous 4 x 4 Latin
      squares, had ad libitum access to bermudagrass or ryegrass-wheat hay without
      supplementation (Control) or with (DM basis) .5% of BW of ground corn (C), .64%
      of BW of rice bran (R), or .25% of BW of corn plus .32% of BW of rice bran (CR).
      Total OM intake with bermudagrass diets was less for R than for C, but values for
      R and C were not different with ryegrass-wheat (forage source x supplement type
      interaction; P < .05). An interaction (P < .06) between supplement type and
      forage source also occurred in digestible OM intake (3.33, 3.66, 2.93, 3.37,
      3.77, 4.04, 3.73, and 3.94 kg/d for Control, C, R, and CR with bermudagrass and
      ryegrass-wheat, respectively). Mature beef cows (504 +/- 25.5 kg BW), in a 6 x 6
      Latin square, were limit-fed ryegrass-wheat and alfalfa hay (3:1; air-dry basis)
      without supplementation (Control) or with (DM basis) .2 or .4% of BW of ground
      corn (L-C and H-C), .26 or .52% of BW of rice bran (L-R and H-R), or .2% of BW of
      corn plus .26% of BW of rice bran (H-CR). Duodenal flows of total (125, 122, 123,
      137, 136, and 129 g/d) and microbial N (63.3, 64.7, 64.8, 70.3, 73.1, and 65.1
      g/d for Control, L-C, H-C, H-R, and H-CR, respectively) were greater (P < .05 and
      .06, respectively) for rice bran than for corn supplements. Crossbred beef steers
      (96; 235 +/- 3.2 kg initial BW) of two frame sizes, with half treated with an
      estrogenic growth promotant, grazed fescue-clover and received Control, L-C, H-C,
      L-R, H-R, and H-CR supplements for 84 d. Supplement amounts were 50% greater
      relative to BW than in the preceding experiment. Overall ADG was increased (P <
      .05) by supplementation and was affected (P < .05) by a supplement type x level
      interaction (.71, .76, .97, .85, .76, and .94 kg/d for Control, L-C, H-C, L-R, H
      R, and H-CR, respectively). Neither frame size nor growth implant modified
      effects of supplement treatments on ADG.

PMID- 8270535
TI  - Supplemental fat and ionophores in finishing diets: feedlot performance and
      ruminal digesta kinetics in steers.
AB  - One feedlot trial (116 d; 192 steers) with a factorial arrangement of treatments
      was conducted to determine effects of supplemental fat and ionophores in corn
      based finishing diets. Factors were level of fat (0 or 4% tallow) and ionophore
      type (none [N], lasalocid [L], monensin plus tylosin [MT], or daily rotation of L
      and MT [LMT]); L, M, and T were fed at 31, 25, and 10 ppm (DM basis),
      respectively. Fat and ionophore interacted for DMI (P < .10), ADG (P < .01), and
      gain:feed G/F, P < .05). Compared with 0%-fat diets, 4% fat decreased (P < .005)
      DMI by steers fed MT by 8.9%. In 0%-fat diets, MT increased (P < .05) ADG and G/F
      compared with N or L; however, this increase was negated or reversed in 4%-fat
      diets. Fat and ionophore interacted (P < .16) on dietary NE concentration. In the
      0%-tallow diet, MT increased NEm and NE(g) by 5.1 and 7.0%, respectively, but MT
      had not effect on NE concentration of the 4%-tallow diet. Alternate feeding of L
      and MT did not increase animal performance above that of separate, continuous
      feeding. Six ruminally fistulated steers were used in a metabolism study to
      evaluate potential mechanisms underlying the interactions observed in the feedlot
      trial. Treatments were the same as the feedlot trial, except that LMT was not
      included. Ruminal digesta kinetics were not altered (P > .30) by the addition of
      fat or ionophores to the diet. Fat and ionophore interacted (P < .05) for molar
      proportions of ruminal acetate and propionate.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270536
TI  - Effects of supplementation on intake, growth rate, and fleece production by
      female Angora kid goats grazing rangeland.
AB  - Ninety-eight and 88 female Angora kid goats (6 mo of age) were grazed/browsed on
      Edwards Plateau rangeland in 92- and 88-d trials in 1989 and 1990, respectively.
      The goats were either not supplemented (negative control, NC) or fed isoenergetic
      amounts of corn (C), a corn/cottonseed meal/molasses mixture (C/CSM), or a
      corn/cottonseed meal/fish meal/molasses mixture (C/CSM/FM). The C/CSM and
      C/CSM/FM supplements provided equal CP but different amounts of ruminally
      undegraded protein (UDP). The goats were allowed to graze/browse in a common
      pasture and were separated into treatment groups three times each week for
      feeding. Intakes of supplement and forage were measured using a dual-marker
      technique. Forage intake was not increased with supplemental feeding (P = .21),
      but tended (P = .08) to be greater with high-protein supplements than with C.
      Total digestible DMI was greater (P < .01) for supplemented goats and was not
      affected by supplement type. Supplemental feeding increased BW gain (P < .01) and
      clean fleece weight (CFW; P < .01). High-protein supplements increased BW gain (P
      < .01), CFW (P = .07), fiber diameter (FD; P < .01), and staple length (P < .01)
      compared with C. Greater amounts of UDP (C/CSM/FM) did not increase BW gain (P =
      .99) but tended to increase CFW (P = .12) and FD (P = .15). Supplemental feeding
      increased total digestible DMI by partial substitution (corn) for forage or
      addition (high-protein supplements) to forage, and both energy and protein
      increased BW gain and CFW and influenced mohair traits.

PMID- 8270537
TI  - Raising replacement beef heifers in the south-birth to parturition: a review of
      current practices.
AB  - The South of the United States (13 southern states) is ecologically and
      socioeconomically well suited for reproducing ruminant animals. The South has a
      broad economic base, its climate is comparatively mild, much of its soil is
      easily eroded requiring vegetative cover, it receives comparatively abundant
      rainfall, and a diversity of plant species grow well, enabling a multitude of
      production and management alternatives. The South currently accounts for 46.3% of
      the beef cows in the United States. To assess current practices associated with
      the raising of replacement beef heifers, a questionnaire was sent to 60 extension
      beef cattle specialists in the 13 southern states. Twenty-four completed
      questionnaires revealed that much needs to be accomplished to improve replacement
      heifer production. Particularly deficient areas include lack of a limited
      breeding season, failure to check for pregnancy, inadequate health management,
      poor nutrition such that heifers do not calve at 24 mo of age, and often those
      that calve do not rebreed. These deficiencies result in reduced economic
      efficiency of replacement heifer development and could result in a significant
      reduction in profits of an entire beef cow-calf operation. Beef cattle
      specialists suggested that part of the problem associated with development of
      replacement heifers is a lack of defined objectives by producers.

PMID- 8270538
TI  - Factors that alter the growth and development of ruminants.
AB  - Growth is defined as an increase in tissue mass. Mass increases by hyperplasia
      early in life and hypertrophy later in life, although hyperplasia of adipose
      tissue continues throughout life. The growth curve, being mass or cumulative
      weight plotted against age, is sigmoid, consisting of a prepubertal accelerating
      phase plus a postpubertal decelerating phase. Mathematically, this curve can be
      described as a function of mature mass, fractional growth rate, and age. At a
      specific fraction of mature mass, body composition seems to be constant, but the
      degree to which nutrition can alter mature mass is not certain. If mature mass is
      altered, body composition at any given mass will be altered. Mature mass can be
      decreased by starvation or protein deficiency early in life. Alternatively,
      retarding the deposition of fat or the administration of estrogenic compounds may
      increase mature protein mass. Many of the advances in rate and efficiency of
      growth and in reduced fat of meat cuts can be explained by increased mature
      protein mass of ruminants. Animals with higher mature weight require more energy
      for maintenance and reach puberty later in life, so a larger mature mass is not
      desirable for the breeding herd. Indeed, smaller replacement heifers would prove
      economical if reproduction were not decreased. A period of restricted growth and
      fat deposition (as on pasture) can increase the slaughter weight of small cattle
      into a more desirable range, presumably through increasing mature protein mass.
      However, calves with retarded growth often make less efficient feedlot gains than
      do calves finished immediately after being weaned. For growing large-framed
      heifers, pasture alone often provides an inadequate energy supply for early
      puberty, but excessive amounts of supplemental feed can enhance fat deposition in
      the udder, which subsequently decreases milk production. By manipulating the
      supply of specific nutrients and hormones, it may prove feasible in the future to
      reduce fat deposition in specific tissues and to alter mature body protein mass.

PMID- 8270539
TI  - Nutritional management of replacement sheep utilizing southern forages: a review.
AB  - Intensive sheep production systems seem to be an appropriate means of fully using
      the available resources, particularly the forages, of the southern region. In
      such systems, ewes should lamb first at approximately 1 yr of age. Programs to
      accomplish this goal must be well-planned and carefully integrated and executed.
      The primary goal is to achieve two-thirds of the ewe's projected mature weight
      before exposure for breeding. General management must reduce heat stress and
      parasitism. Forage quality must be maintained at a level consistent with National
      Research Council requirements for energy and protein. Protein is not normally a
      limiting factor. Energy supplementation and grazing pressure can be used to
      maintain growth without over-condition, which reduces subsequent performance.

PMID- 8270540
TI  - Nutritional management of replacement beef heifers: a review.
AB  - Systems to produce replacement heifers to calve initially at 2 yr of age and at
      12-mo intervals thereafter require integrated forage-animal management plans. The
      process of developing heifers as replacements must begin during the cow-calf
      production phase. Age and weight at puberty are affected by several factors,
      including breed of livestock. Generally, breeds of a larger size at maturity are
      older and heavier when reaching puberty. Heifers that are kept as replacements
      must be weaned at relatively heavy weights in comparison to their expected mature
      body size without becoming obese. Excessive adipose tissue in heifers during the
      preweaning phase may result in reduced subsequent performance of these animals.
      Several management techniques were reviewed that can be used both pre- and
      postweaning, including using anthelmintics, anabolic growth implants, and
      ionophores. Anabolic growth implants can increase heifer rates of gain and
      increase pelvic size. In addition, there are indications that these implants may
      alter mammary gland development, which may subsequently increase milk production.
      Ionophores were shown to increase growth rates, particularly in grazing heifers
      but more importantly to decrease age at puberty. Age and weight at puberty have
      been shown to be affected by level of nutrition. It is preferable for heifers to
      reach puberty one or two estrous cycles before the breeding season, and the
      breeding season for heifers should begin > or = 21 d before the breeding season
      of the mature cow herd. This time difference allows for the generally longer
      postpartum interval for primiparous cows than for multiparous cows. Because of
      the limited opportunities (every 12 mo) for cows to calve, optimum efficiency
      must be pursued.

PMID- 8270541
TI  - Managing replacement stock within the environment of the south--plant, soil, and
      animal interactions: a review.
AB  - The South extends from the Atlantic Coast and the Gulf of Mexico north through
      Virginia and Kentucky and west to the 100th meridian, which extends through Texas
      and Oklahoma. The soils, environment, and range of adapted forage species offer
      many and varied opportunities for designing forage-livestock systems for rearing
      replacement stock. Anti-quality factors of concern when using forages for
      replacement stock include the presence of Acremonium coenophialum (Morgan-Jones
      and Gams) in tall fescue (Festuca arundinacea Schreb.), phytoestrogens
      potentially in several species of Trifolium and Medicago, toxins in some species
      of brush that contribute to infertility, and imbalances of several minerals
      including Ca, P, K, Fe, I, Zn, Na, Cu, and Se. Systems should be designed to
      provide appropriate quality and quantity of forage to produce reproductively
      active female animals of the desired weight and condition for breeding at the
      target age, usually 15 mo for beef and dairy heifers and 8 to 9 mo for ewe lambs.
      Systems generally require sequence grazing of two or more forage species or
      mixtures to provide extended or year-round grazing opportunities. Stockpiling of
      tall fescue in the Upper South and use of cool-season annuals in the Lower South
      extend grazing in autumn, winter, and early spring. Successful systems coordinate
      plant growth potential with changing animal forage requirements for both quantity
      and quality of forage to achieve optimum growth rates for replacement stock.

PMID- 8270542
TI  - Rapid communication: cloning and sequence analysis of the swine Oct-2 POU-domain
      genomic region.

PMID- 8270543
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM002.

PMID- 8270544
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM003.

PMID- 8270545
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM004.

PMID- 8270546
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM006.

PMID- 8270547
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM028.

PMID- 8270548
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM067.

PMID- 8270549
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM074.

PMID- 8270550
TI  - Rapid communication: bovine dinucleotide repeat polymorphism RM106.

PMID- 8270551
TI  - Infections via respiratory equipment: a potential hazard.

PMID- 8270552
TI  - Post-transfusion hepatitis--now HCV, how many more?

PMID- 8270553
TI  - Bacteriology of spirometer tubing and evaluation of methodology to prevent
      transmission of infection.
AB  - Transmission of respiratory infection by a spirometer is a definite risk in
      countries like India where a majority of respiratory diseases are infective in
      nature. To assess this problem, scrapings and washing from a spirometer tube in
      regular use were taken for microbiological studies. Significant bacterial growth
      on culture included Aspergillus and acid fast bacilli. In order to check
      contamination, a segregation chamber was attached to the spirometer. Twenty-three
      patients used the spirometer with or without segregation chamber and a good
      correlation was shown between the two methods in forced expiratory volume in one
      second (r = 0.94), forced vital capacity (r = 0.92) and mid maximum expiratory
      flow rate (r = 0.90). It can be concluded that a spirometer may have significant
      growth of pathogenic bacteria and a segregation chamber may be used routinely
      with the spirometer in order to prevent its contamination.

PMID- 8270554
TI  - Antibody to hepatitis-C virus in multi-transfused thalassaemics--Indian
      experience.
AB  - Twelve out of 72 (16.7%) multi-transfused patients with thalassemia major (age
      range: 7-22 years) were found to be positive for antibody to hepatitis-C virus
      (anti-HCV). Nine (75%) of these 12 cases were positive for hepatitis B core
      antibody (anti-HBc) and/or hepatitis B surface antibody (anti-HBs). Out of the
      remaining 60 patients (83.3%), 27 patients (45%) were positive for anti-HBc
      and/or anti-HBs, while six (10%) were HBsAg positive Anti-HCV positive patients
      had significant higher levels of liver enzymes than those who were negative (p <
      0.01). S. Ferritin was also significantly higher in those with seropositivity for
      anti-HCV than those who were negative (p < 0.01). It is concluded that HCV
      (besides HBV) is a major problem in multi-transfused thalassemia major patients
      and routine pre-transfusion screening of blood for anti-HCV must be introduced in
      the blood banks.

PMID- 8270555
TI  - Is a hypertensive always a hypertensive?
AB  - Forty two patients of uncomplicated essential hypertension with well controlled
      and stable blood pressure for the last six months have been followed up for 2
      years after withdrawal of therapy. Drug therapy was reinstituted if they became
      hypertensive again. Thirty four (89.9%) and 33 patients remained normotensive at
      4 and 8 weeks respectively. At the end of 6 months, 26 (61.9%) patients were drug
      free, 9 (21.4%) were back on therapy and 7 (16.5%) were lost to follow up. At the
      end of one year, 18 (42.8%) were drug free, 14 (33.3%) were on drugs and 10
      (23.8%) had dropped out. At the end of 2 years, the figures were 14 (drug free),
      15 (on drugs) and 13 (drop-outs). No cardiovascular or any other complication was
      recorded during the period. These observations suggest that there may be a
      subgroup of mild or moderate hypertensives in whom it may be possible to withdraw
      therapy under observation. However, there is a risk of substantial drop out rate
      possibly under a false sense of security. Considering the large number of
      hypertensives in our country and the world over, its economic and therapeutic
      implications are obvious.

PMID- 8270556
TI  - Obstructive jaundice--a diagnostic appraisal.
AB  - One hundred and eight suspected cases of obstructive jaundice (OJ) were analysed
      using ultrasonography, percutaneous transhepatic cholangiography (PTC) or
      Endoscopic retrograde cholangiopancreatography (ERCP) or both. Clinical
      evaluation had accuracy of 93% in identifying OJ and establishing aetiology in
      62%, however, it lacked specificity. Ultrasonography was useful in
      differentiating obstructive jaundice from medical jaundice in 91% of cases.
      However, the cause and site of biliary obstruction could be identified in 55% and
      46% respectively. PTC was helpful in detecting the site of obstruction in 80.4%
      and nature in 63% of cases. Its failures were mostly associated with the presence
      of metastasis in the liver. ERCP successfully attained cholangiography in 58% and
      pancreatogram in 70% of cases. Overall diagnostic yield of ERCP was 67% in view
      of additional endoscopic findings in 18 cases. The complications were occasional
      and could be managed effectively with medical treatment. This study suggests
      utility of clinical evaluation in OJ inspite of its poor specificity and
      comparative value of PTC and ERCP in establishing the site as well as nature of
      lesion.

PMID- 8270557
TI  - Circadian rhythm in acute stroke.
AB  - Ischemic events have been reported to follow a circadian rhythm. The frequency of
      myocardial infarction is found to be increased between 6:01 a.m. and 2:00 p.m.
      Blood pressure also demonstrates a similar circadian variation. Circadian
      variation of stroke onset has also been reported, but with contradictory
      findings. To determine this in the Indian population, we studied 182 consecutive
      patients of acute stroke admitted to our words within twelve hours of onset. The
      frequency of onset of stroke was found to be highest between 6:01 am and 2:00 pm,
      in patients of infarct as well as haemorrhage. Patients of hypertension also
      showed a similar variation. Thus, the identification of periods of high risk, may
      help by matching drug doses with periods of vulnerability.

PMID- 8270558
TI  - False positive ECG and coronary heart disease.
AB  - In 1983, we carried out a cross-sectional, rural community based study and
      highlighted an abysmally low prevalence of probable coronary heart disease in
      resting electrocardiogram. A seven year follow-up (1983-1990) of 179 suspects
      showed no morbidity or mortality from coronary heart disease. Eighty one out of
      98 suspects tested negative on a symptom limited maximal exercise test. Though
      seventeen suspects had an asymptomatic exercise-induced ST depression (> 1.0 mm)
      their haemodynamic response to exercise and effort tolerance was excellent. Of
      the twelve subjects who took a repeat exercise test six months later, eleven
      failed to show ST depression on exercise. We attribute the false positivity of
      exercise test and its poor reproducibility to labile electrocardiographic changes
      unmasked by exercise.

PMID- 8270559
TI  - M-mode echocardiographic diagnosis of left ventricular hypertrophy.
AB  - To assess the utility of various primary and derived M-Mode Echocardiographic
      parameters for the purpose of defining left ventricular hypertrophy (LVH), 74
      subjects with LVH were subjected to M-mode echocardiographic examination. It was
      concluded that except for cross sectional area, the other echocardiographic
      parameters performed too poorly to be of any clinical utility for defining LVH by
      echocardiography.

PMID- 8270560
TI  - Menarcheal age in relation to ABO blood group phenotypes and haemoglobin-E
      genotypes.
AB  - The age at menarche in relation to ABO blood group phenotypes and haemoglobin-E
      genotypes has been studied among 290 girls belonging to Mongoloid ethnic stock in
      the North Eastern region of India. The study shows that the age at menarche is
      influenced by the abnormal haemoglobin E genotype as well as ABO blood group
      phenotype. Thus, the genetic markers play a pivotal role in the growth and
      development of an individual.

PMID- 8270561
TI  - Colchicine in diabetes mellitus.
AB  - As anti-inflammatory drugs such as acetylsalicylic acid are known to partially
      restore insulin response to glucose, the possible beneficial effect of
      colchicine, an anti-gout and anti-inflammatory drug, in non-insulin dependent
      diabetes mellitus (NIDDM) was studied. Colchicine could significantly reduce
      blood glucose levels, both fasting and post-prandial when given at a dose of 0.5
      mg thrice a day in NIDDM patients. There were no side-effects due to the therapy.
      This study suggests that colchicine has anti-diabetic properties.

PMID- 8270562
TI  - Artificial heart--current status.

PMID- 8270563
TI  - T-wave changes during normal conduction in intermittent left bundle branch block.

PMID- 8270564
TI  - Cardio-vascular and respiratory manifestations in tobacco chewers.

PMID- 8270565
TI  - Haloperidol with nitrazepam poisoning.

PMID- 8270566
TI  - Pathophysiology and treatment of spasticity.

PMID- 8270567
TI  - Routine use of fruits as co-prescription.

PMID- 8270568
TI  - Aluminium phosphide poisoning.

PMID- 8270569
TI  - Coronary prone behaviour pattern and ischaemic heart disease.

PMID- 8270570
TI  - Insulin requirement formula.

PMID- 8270571
TI  - Diuretic induced hyponatremia in elderly.

PMID- 8270572
TI  - Limitation of cardiothoracic ratio (CTR) in chronic obstructive airways disease
      (COAD)

PMID- 8270573
TI  - Sleep disorders in India.

PMID- 8270574
TI  - Enalapril in hypertension.

PMID- 8270575
TI  - Pyridoxine and isonex.

PMID- 8270576
TI  - Recurrent chest infection--sole manifestation of oesophageal achalasia in a
      child.

PMID- 8270577
TI  - Spontaneous cerebellar haematoma treated conservatively.

PMID- 8270578
TI  - Multicystic cavernous haemangioma liver.

PMID- 8270579
TI  - Cutaneous hypersensitivity to co-trimoxazole after autologus bone marrow
      transplantation and immunotherapy with interferon alpha-2A and interleukin-2.
AB  - Typical cutaneous hypersensitivity reaction to co-trimoxazole was seen in a woman
      after autologous bone marrow transplantation and immunotherapy. She had developed
      no such reaction during chemotherapy prior to the transplant or immediately after
      the transplant. The immunoperturbed state that exists for a period of time after
      bone marrow transplantation, especially in the presence of immunomodulation
      caused by combined therapy with recombinant human interferon alpha and
      interleukin-2, with exposure to potentially reaginic agents may have contributed
      to the development of the hypersensitivity reaction in this patient.

PMID- 8270580
TI  - Invasive pulmonary aspergillosis and nocardiosis in an immunocompromised host.
AB  - A case of invasive pulmonary aspergillosis and nocardiosis following high dose
      prolonged steroid therapy given for suspected rapidly progressive
      glomerulonephritis is reported. A favourable response was achieved with a
      combination of amphotericin B and cotrimoxazole. A high index of suspicion and
      aggressive investigations are necessary for confirmation of diagnosis and early
      institution of appropriate therapy.

PMID- 8270581
TI  - Hyperkalemic periodic paralysis associated with thyrotoxicosis.
AB  - A 32 year old male presented with episodic pure motor weakness for 1 1/2 months.
      On evaluation he was found to be thyrotoxic. Hyperkalemic challenge test provoked
      similar weakness with raised serum potassium (6 meq/L). He responded to treatment
      with neomercazole. Till he became euthyroid, he responded to the addition of
      acetazolamide to his medication. He is symptom free on antithyroid drug alone
      over 8 months of follow up.

PMID- 8270582
TI  - AIDS-associated Kaposi's sarcoma in an Indian female.
AB  - We report the first case of AIDS-associated Kaposi's Sarcoma in a 35 year old
      Indian female, a commercial sex worker, with lesions involving skin and mucous
      membranes. Diagnosis was confirmed on histopathology, electron microscopy,
      seropositivity, (ELISA and Western Blot) as well as Pepti-LAV test and viral
      culture. Antibodies to human immunodeficiency virus, both HIV-1 & 2, were
      present. HLA DR5,7 was positive on oligotyping. Genetic predisposition,
      therefore, may be suspected.

PMID- 8270583
TI  - The economic burden of depression in 1990.
AB  - BACKGROUND: We estimate in dollar terms the economic burden of depression in the
      United States on an annual basis. METHOD: Using a human capital approach, we
      develop prevalence-based estimates of three major cost-of-illness categories: (1)
      direct costs of medical, psychiatric, and pharmacologic care; (2) mortality costs
      arising from depression-related suicides; and (3) morbidity costs associated with
      depression in the workplace. With respect to the latter category, we extend
      traditional cost-of-illness research to include not only the costs arising from
      excess absenteeism of depressed workers, but also the reductions in their
      productive capacity while at work during episodes of the illness. RESULTS: We
      estimate that the annual costs of depression in the United States total
      approximately $43.7 billion. Of this total, $12.4 billion-28%-is attributable to
      direct costs, $7.5 billion-17%-comprises mortality costs, and $23.8 billion-55%
      is derived from the two morbidity cost categories. CONCLUSION: Depression imposes
      significant annual costs on society. Because there are many important categories
      of cost that have yet to be estimated, the true burden of this illness may be
      even greater than is implied by our estimate. Future research on the total costs
      of depression may include attention to the comorbidity costs of this illness with
      a variety of other diseases, reductions in the quality of life experienced by
      sufferers, and added out-of-pocket costs resulting from the effects of this
      illness, including those related to household services. Finally, it may be useful
      to estimate the additional costs associated with expanding the definition of
      depression to include individuals who suffer from only some of the symptoms of
      this illness.

PMID- 8270584
TI  - Depression: a neglected major illness.
AB  - BACKGROUND: To illustrate the burden depression imposes on society, we present
      estimates of the annual costs of depression--$44 billion--as well as the number
      of individuals it affects per year--almost 11 million. Although these estimates
      point to depression as a major illness, this study examines why it is not
      generally considered as such by the medical and public health communities or by
      society at large. METHOD: We develop a framework that compares depression with
      major illnesses such as coronary heart disease, cancer, and AIDS by highlighting
      salient characteristics of each illness. This comparative illness framework
      considers the costs, prevalence, distribution of sufferers, mortality,
      recognition, and treatability of each disease. This comparison underscores many
      of the similarities and differences among the illnesses examined. RESULTS:
      Because depression often is not properly recognized and begins to affect many
      people at a relatively early age, it exacts costs over a longer period of time
      and in a more subtle manner than other major illnesses. It also imposes a
      particularly heavy burden on employers in the form of higher workplace costs.
      CONCLUSION: We conclude that, because of the potential for successful treatment,
      increased attempts to reach untreated sufferers of depression appear to be
      warranted. Employers as a group have a particular incentive to invest in the
      recognition and treatment of this widespread problem, in order to reduce the
      substantial costs it imposes upon them each year.

PMID- 8270585
TI  - The costs of treating depression.

PMID- 8270586
TI  - Electroconvulsive therapy in patients taking theophylline.
AB  - BACKGROUND: Initiating a course of electroconvulsive therapy (ECT) in patients
      taking theophylline has been associated with status epilepticus and consequent
      brain damage or even death. However, some patients with severe pulmonary
      conditions may both require theophylline and be seriously depressed enough to
      warrant ECT. Deciding whether to use ECT in such patients is a fairly common
      clinical problem. METHOD: The records of seven patients taking theophylline
      during nine courses of ECT were reviewed to ascertain whether inordinately long
      seizures occurred. RESULTS: In 77 documented seizures, there was one 190-second
      seizure as measured by EEG. All others were shorter than 100 seconds, and mean
      motor and EEG seizure lengths were comparable with those reported in the
      literature. CONCLUSION: Theophylline coadministration is a risk factor for
      prolonged seizures in patients starting a course of ECT. However, in most
      severely depressed, medication-refractory patients, a course of ECT can be
      undertaken with safety. Precautions that can decrease the risk of prolonged
      seizures are discussed.

PMID- 8270587
TI  - SSRI-associated nocturnal bruxism in four patients.
AB  - BACKGROUND: Nocturnal bruxism (tooth clenching and/or grinding during sleep)
      affects a significant proportion of the population. Its etiology remains
      uncertain, and no entirely satisfactory treatment is available. METHOD: This is
      an observational report of four depressed individuals selected from one
      psychiatrist's practice within an urban hospital's psychopharmacology clinic.
      Psychiatric diagnoses were made according to DSM-III-R criteria. Nocturnal
      bruxism was determined on the basis of dental examination and/or self-reported
      nocturnal tooth clenching and/or grinding. RESULTS: Four patients developed
      nocturnal bruxism within 2 to 4 weeks after initiation of treatment with
      fluoxetine or sertraline. Bruxism remitted in all patients after a decrease in
      antidepressant dosage (N = 1) or addition of buspirone (N = 3). CONCLUSION: These
      observations, which should be confirmed by a controlled study, suggest an
      association between serotonin selective reuptake inhibitor (SSRI) treatment and
      the onset or exacerbation of nocturnal bruxism. In addition, they suggest that a
      decrease in SSRI dosage or the addition of buspirone may relieve SSRI-associated
      nocturnal bruxism.

PMID- 8270588
TI  - Use of low-dose fluoxetine in major depression and panic disorder.
AB  - BACKGROUND: Recent reports suggest that fluoxetine in doses less than the
      standard 20 mg/day may be effective in the treatment of depression and that some
      patients, particularly those with panic disorder, may be intolerant of the 20
      mg/day dose. We examined the utility of starting fluoxetine at a low daily dose
      (5 mg) and increasing to the standard daily dose (20 mg) in depressed outpatients
      with and without concurrent panic disorder. METHOD: One hundred thirty-three
      consecutive outpatients meeting DSM-III-R criteria for major depression were
      studied. Patients were started on fluoxetine 5 mg/day and were gradually
      increased to 20 mg/day over a 1-week period. Patients who were unable to reach
      the 20 mg/day dose were instructed to take the highest tolerable dose for the
      duration of the study. After a month of fluoxetine treatment, patients were
      evaluated for compliance with treatment and improvement on the Clinical Global
      Improvement scale. RESULTS: Twenty-eight percent of the patients were unable to
      increase the dose to the full 20 mg. Of these patients, half could not tolerate
      doses lower than 20 mg and discontinued the drug, while the other half did well
      clinically on the lower doses. Patients who discontinued fluoxetine tended to
      have panic disorder in addition to depression. CONCLUSION: We conclude that
      starting fluoxetine at doses lower than 20 mg is a useful strategy because of the
      substantial fraction of patients who cannot tolerate a 20-mg dose but appear to
      benefit from lower doses. This dosing strategy may be of particular benefit for
      patients with panic disorder.

PMID- 8270589
TI  - Resolution of polydipsia and hyponatremia in schizophrenic patients after
      clozapine treatment.

PMID- 8270590
TI  - Slow eating: OCD or simple phobia?

PMID- 8270591
TI  - A case of phenobarbital behavioral toxicity presenting as a menstrually related
      mood disorder.

PMID- 8270592
TI  - Electroconvulsive therapy as a treatment for recurrent depression.

PMID- 8270593
TI  - The neuroanatomy of depression.
AB  - Findings from computed tomography (CT), magnetic resonance imaging (MRI),
      positron emission tomography (PET), and single photon emission computed
      tomography (SPECT) studies of patients with depression suggest that this mood
      disorder is associated with regional brain dysfunction. The various elements of
      depression--dysphoria, anhedonia, helplessness, and sad affect--are all closely
      associated with changes in cerebral blood flow and/or metabolism in the frontal
      temporal cortex and caudate nucleus. A compelling convergence of information from
      psychiatric and neurologic investigations indicates that depression is mediated
      by a restricted set of brain structures.

PMID- 8270594
TI  - Functional brain imaging in late-life depression and dementia.
AB  - Studies utilizing advanced scanning technologies suggest that brain imaging may
      have a role in the differential diagnosis of some common neuropsychiatric
      disorders. In subjects with dementia of the Alzheimer type (DAT), widespread
      cortical reductions in glucose metabolism and blood flow have been described,
      with predominant involvement of the temporal and parietal lobes. The primary
      sensory areas and subcortical regions are relatively spared. When a "patchy"
      pattern of reductions in cerebral blood flow and metabolism is associated with
      clinical dementia, a vascular etiology should be suspected. Major depression in
      the elderly is associated with reductions in whole brain glucose metabolic rates
      comparable in magnitude with those described in DAT. Relatively distinctive
      patterns of flow and metabolism also are seen in frontal-temporal dementia and
      Parkinson's disease with dementia.

PMID- 8270595
TI  - PET and SPECT: opportunities and challenges for psychiatry.
AB  - Positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) are the most advanced technologies available for the functional imaging
      of the brain, surpassing magnetic resonance imaging (MRI) and computed tomography
      (CT) scanners in potential clinical and research applications in neuropsychiatry.
      PET deals with a small number of radionuclides with short physical half-lives and
      an exclusive energy of 511 keV; SPECT utilizes an ensemble of radionuclides that
      exhibit moderate physical half-lives, each with its own characteristic spectrum
      of energy. PET imaging instrumentation requires substantial refinements to enable
      utilization with high-energy photons, larger data sets, and a high magnitude of
      information flow per unit of time. The instrumentation enables greater
      sensitivity and resolution, as compared with SPECT, but requires a more extensive
      data acquisition and processing infrastructure, resulting in a significantly
      higher system cost. SPECT has a number of price/performance alternatives in
      configuring a system, and has further cost advantages in that it utilizes widely
      available chemical tracers.

PMID- 8270596
TI  - SPECT imaging in psychiatry: introduction and overview.
AB  - Positron emission tomography (PET) and single photon emission computed tomography
      (SPECT) use advanced computer image construction techniques to illustrate
      regional cerebral function, metabolism, and chemistry. Although the resolution of
      PET is higher than that of SPECT, and the technical development of SPECT has
      lagged behind that of PET, SPECT has recently enjoyed increasingly widespread
      use, particularly because its costs and technology are within the reach of all
      clinical nuclear medicine facilities. SPECT imaging agents have greater half
      lives than those used with PET, thereby permitting longer and more detailed
      neurochemistry study than is possible with PET. The research value of both
      methods has unique potential compared with computed tomography (CT) and magnetic
      resonance imaging (MRI), which traditionally have provided a static image of the
      brain's structure or anatomy.

PMID- 8270597
TI  - SPECT and PET imaging in mood disorders.
AB  - Single photon emission computed tomography (SPECT) and positron emission
      tomography (PET) studies are yielding a picture of clinical depression as a
      disorder associated with dysfunction in specific brain regions. These data
      support the view of depression as a disease of the brain in general and of the
      frontal and temporal lobes in particular. Frontal lobe hypometabolism is emerging
      as a common final pathway for most types of primary and secondary depression,
      regardless of the original cause. The severity of depression is often related to
      the degree of frontal hypometabolism, and preliminary studies indicate that the
      hypometabolism normalizes after treatment in concert with the patient's improved
      mood. Primary depression also is associated with abnormal activation of key brain
      areas, including discrete aspects of the frontal and temporal lobes, the
      amygdala, and the cingulate gyrus. Several areas of research are currently under
      way using SPECT or PET to explore further the neuroanatomy of depression.

PMID- 8270598
TI  - The role of cryosurgery in the treatment of hepatic cancer: a report of 113
      cases.
AB  - From November 1973 to June 1992, cryosurgery with liquid nitrogen (-196 degrees
      C) was performed on 113 patients with hepatic cancer, including 107 patients with
      primary liver cancer (PLC) and 6 patients with secondary liver cancer (SLC). Of
      the 107 PLC patients, the subclinical stage constituted 30.8% (33/107), the
      moderate stage 61.7% (66/107), and the late stage 7.5% (8/107). There were 32
      cases with small PLC (up to 5 cm). Liver cirrhosis was observed in 86.0%
      (92/107). We designed flat cryoprobes for freezing tumors deep within the hepatic
      parenchyma. Intraoperative ultrasound was used for monitoring hepatic
      cryolesions. There were no operative mortalities and complications, such as
      rupture of a tumor, delayed bleeding, or bile leakage. The 5-year and 10-year
      survival rates were 22.0% and 8.2%, respectively, for the 107 PLC patients and
      48.8% and 17.1%, respectively, for the 32 patients with small PLC. Of the 6 SLC
      patients, survival ranged from 2 months to 90 months (average, 23.2 months). One
      SLC patient has been well for 7 years and 6 months after cryosurgery. These
      results indicate that cryosurgery, the in situ freezing of cancer, is a safe and
      effective treatment for unresectable hepatic cancer.

PMID- 8270599
TI  - Glutathione S-transferase activity in patients with cancer of the digestive
      tract.
AB  - Glutathione S-transferase (GST) and carcinoembryonic antigen were measured in the
      plasma of 95 patients with neoplasm of digestive tract, in 40 patients suffering
      from non-neoplastic diseases and in 40 healthy subjects. The mean value of the
      GST activity was significantly (P < 0.001) elevated in patients with gastric,
      liver and colorectal cancer (10.4 U/l, 14.1 U/l and 12.3 U/l respectively) as
      compared with the reference population (3.2 U/l). GST elevations above normal
      were observed in 26 (90%) patients with gastric cancer, in 18 (100%) with liver
      cancer and in 25 (89%) with colorectal cancer. Carcinoembryonic antigen appeared
      less sensitive. In 15 patients the postoperative levels of serum GST were
      increased after surgery then gradually declined and after 1 month showed a
      normalization in 10 patients. Our data suggest that GST measurement may be useful
      as a tumour marker in gastric, liver and colorectal cancer. Moreover the combined
      determination of GST and other markers increase the sensitivity for cancer
      detection.

PMID- 8270600
TI  - Suppressed cellular immunity in patients with nasopharyngeal carcinoma.
AB  - The subsets and functions of lymphocytes were investigated in patients with
      nasopharyngeal carcinoma (NPC). The patients were divided into two groups
      comprising tumor-bearing patients and those in remission. There was no difference
      in the proportion of T cells among tumor-bearing, remission and healthy control
      groups. The percentages of inducer/helper T cells and natural killer cells were
      smaller in the tumor-bearing group than in the control group whereas the
      percentage of suppressor T cells was greater in the tumor-bearing group.
      Phytohemagglutinin-stimulated blastogenesis was markedly suppressed in the tumor
      bearing group. The responsiveness to interleukin-2 of blastogenesis and of
      natural killer and lymphokine-activated killer activities was lowered in the
      tumor-bearing group. These parameters in the remission group were intermediate
      between those of the tumor-bearing and control groups. These results suggest that
      cellular immunity is suppressed in patients with NPC and that the suppressed
      condition still remains even in remission. Immunotherapy is considered to be
      indispensable for the proper treatment of NPC.

PMID- 8270601
TI  - Report from the 29th annual meeting of the American Society of Clinical Oncology,
      16-18 May 1993, Orlando, Florida.

PMID- 8270602
TI  - Differential antitumor activity and toxicity of isomeric 1,2-diaminocyclohexane
      platinum (II) complexes.
AB  - Acquired resistance is a main drawback of using cisplatin in cancer chemotherapy;
      however, analogs containing the 1,2-diaminocyclohexane (DACH) ligand can overcome
      this resistance. Because DACH can exist as the trans-1R,2R, trans-1S,2S or cis
      isomer, the antitumor activity and toxicity of individual isomers of both
      DACH(sulfato)Pt(II) and DACH(1,1-cyclobutanedicarboxylato)Pt(II) complexes have
      been examined. At optimal doses, differences in antitumor activities among the
      three isomers were moderately dependent on the in vivo tumor models (L1210/0,
      L1210/DDP, B16 and M5076). However, differences in efficacy among these isomers
      were greatly modulated by the sulfate or 1,1-cyclobutanedicarboxylate (CBDCA)
      leaving ligands. Thus, the trans isomers (R,R and/or S,S) of the sulfate complex
      generally had greater activities than the corresponding cis form, while the cis
      configuration appeared to be superior in the complex containing the CBDCA ligand.
      The isomers were also compared for their potential to elicit myelosuppression and
      kidney toxicity. Of the six isomers investigated, cis-DACH(CBDCA)Pt(II) was
      myelosuppressive, and the corresponding R,R and S,S isomers were mildly
      nephrotoxic. No such toxicities were apparent with any of the sulfate complexes.
      From these studies, particularly with the cisplatin-resistant L1210/DDP cell
      line, the R,R isomers are evidently the most interesting. However, it is possible
      that other leaving ligands or tumor models may indicate either S,S- or cis-DACH
      as the isomer worthy of greater interest.

PMID- 8270603
TI  - Inhibitory effects by oral administration of ginsenoside Rh2 on the growth of
      human ovarian cancer cells in nude mice.
AB  - Recently two new compounds, ginsenosides Rh1 and Rh2, have been isolated from an
      ethanol extract of the processed root of Panax ginseng CA Meyer, and Rh2 (but not
      Rh1) has been found to cause growth inhibition of cultured B16 melanoma cells. We
      have also demonstrated that Rh2 caused inhibition of cultured human ovarian
      cancer cell (HRA) proliferation. The effect of oral administration of Rh2 on
      tumor growth and survival of nude mice bearing HRA cells was examined. Nude mice
      were inoculated subcutaneously in the right flank with 10(6) HRA cells. After 7
      days of tumor inoculation 2 mg/kg cis-diamminedichloroplatinum(II) (cisplatin)
      was administered intraperitoneally once a week for 5 weeks. In Rh2-treated
      groups. Rh2 was dissolved in absolute ethanol, adjusted with distilled water to
      1, 15, and 120 microM, and 0.4 ml of each concentration was administered orally
      by canula every day for 90 days, from the next day of tumor inoculation. The
      tumor volume, hematocrit and body weight were measured every week. On days 56 and
      63 after tumor inoculation, the tumor volumes in all groups treated with Rh2 were
      significantly less than those in an ethanol-treated control group and also in
      cisplatin treated group. After 70 days, the tumor growth in nude mice treated
      with 15 microM and 120 microM Rh2 was significantly inhibited compared to that in
      a cisplatin treated group as well as a control group. Consequently, the survival
      of nude mice treated with 15 microM and 120 microM Rh2 was also significantly
      prolonged, compared to that of cisplatin treated mice. No toxic effects were
      observed in any of the mice.

PMID- 8270604
TI  - Effects of interferon gamma on the proliferation and modulation of cell-surface
      structures of human ovarian carcinoma cell lines.
AB  - Platinum-containing regimens are very effective in the primary treatment of
      ovarian cancer. However, upon subsequent treatment most tumors develop multidrug
      resistance. The clinical application of biological response modifiers like
      interferon gamma (IFN gamma) in advanced ovarian cancer is therefore of
      increasing interest. Permanent ovarian cancer cell lines are suitable for
      investigating the mode of action and the potential clinical effectiveness of such
      response modifiers. IFN gamma is known to modulate many cellular functions. In
      this study it was compared for its antiproliferative and antigen-modulatory
      activity on the expression of tumor-associated (CA-125, HMFG, CEA) and major
      histocompatibility complex (MHC) class I and II antigens as well as of the
      epidermal growth factor (EGF) receptor on 20 newly established human ovarian
      carcinoma cell lines. IFN gamma in concentrations of 10, 50 and 100 U/ml was used
      to study its antigen-modulatory effect, and at additional 1 U/ml and 1000 U/ml to
      assess its antiproliferative effect on the cells. The cells were incubated with
      IFN for 4 days. Two cell lines showed strong antiproliferative activity even at
      minimal doses (up to 50 U/ml). Intermediate growth inhibition between 34% and 84%
      was observed in 15 cell lines with higher doses. Three lines were resistant to
      IFN gamma. Independent of the antiproliferative effect, IFN gamma enhanced the
      expression of MHC class I and MHC class II in nearly all cell lines. Upregulation
      was also observed for most of the tumor-associated antigens (TAA) and EGF
      receptor expression. A down-regulation was noticed but rarely. The fact that IFN
      gamma showed an antiproliferative activity on the majority of the cell lines is
      of clinical relevance. The in vitro modulation of cell-surface determinants by
      IFN gamma warrants special attention. The enhanced expression of TAA and MHC
      antigens can improve immunogenicity of the tumor cells and may explain the
      therapeutic effects observed under IFN therapy in ovarian cancer. By contrast,
      enhanced expression of the EGF receptor, often associated with poor patient
      survival rates, may be an undesirable side-effect of IFN therapy.

PMID- 8270605
TI  - Patient choice, cost, and survival of critically ill cancer patients: a societal
      dilemma.

PMID- 8270606
TI  - Immunohistochemical localization of collagenous proteins in cartilaginous tumors:
      characteristic distribution of type IX collagen.
AB  - The distinctive tissue localization of collagen types, particularly of type IX
      collagen in human cartilaginous tumors (10 cases of enchondroma and 15 cases of
      chondrosarcoma including 3 cases of secondary chondrosarcoma) was examined
      immunohistochemically using affinity-purified antibodies against types I, II,
      III, V, VI, and IX collagen, in comparison with that in human fetal cartilage. In
      fetal cartilage matrix, types II and IX collagen were diffusely distributed,
      while types I, III, and V collagens were not present. In the matrices of
      enchondromas and primary chondrosarcomas, types II and IX collagens were also
      diffusely distributed, but with some areas of irregular type IX collagen
      deposits. The secondary chondrosarcoma simulated normal fetal cartilage in the
      distribution pattern of types II and IX collagen, unlike the pattern in primary
      chondrosarcoma, where types II and IX collagen were decreased and poorly
      immunostained, whereas non-cartilaginous interstitial collagens (I, III, and V)
      appeared diffusely in the matrix, increasing with the grade of malignancy. These
      findings suggest that neoplastic cartilage is characterized initially by an
      uneven distribution of type IX collagen, prior to any alteration of other types
      of collagen; the diverse expressions of intercellular components in cartilaginous
      tumors may be one indicator for malignancy.

PMID- 8270607
TI  - Acute effects of 4-ipomeanol on experimental lung tumors with bronchiolar or
      alveolar cell features in Syrian hamsters or C3H/HeNCr mice.
AB  - 4-Ipomenaol (IPO) has been shown to induce P-450-mediated necrosis of Clara cells
      in experimental animals, and clinical trials were initiated to treat people with
      bronchioloalveolar cancers with this novel drug. We therefore performed
      experiments to examine two different animal lung tumor models for acute IPO
      cytotoxicity: hamster Clara-cell-derived adenocarcinomas and mouse alveolar type
      II cell tumors. Clara cells serve as stem cells for airway cell renewal and,
      therefore, tumors derived from Clara cells may likewise differentiate into
      various bronchiolar cell types, or undergo squamous cell metaplasia. Bronchiolar
      cell tumors were induced in Syrian hamsters by a single weekly gavage with 6.8 mg
      N-nitrosomethyl-n-heptylamine (NMHA)/animal for 35 weeks. NMHA-induced
      bronchiolar tumors were classified as well-differentiated lepidic
      bronchioloalveolar carcinomas, acinar adenocarcinoma, adenosquamous carcinoma,
      and squamous-cell carcinoma. After 35 and 46 experimental weeks, control and
      carcinogen-treated hamsters were injected once with doses of 40-110 mg IPO/kg
      i.p. and necropsied 15-48 h later. Solid and papillary tumors with alveolar cell
      features were induced transplacentally in C3H/HeNCr mice, by treating pregnant
      animals on gestation day 16 with 0.5 mmol N-nitrosoethylurea/kg, i.p. Offspring
      of control and carcinogen-treated mice were injected at 2-3 months of age with 35
      mg or 50 mg IPO/kg i.p. and necropsied either 24-48 h or 5 and 12 days after
      injection. Light microscopic studies were carried out to assess cytotoxic effects
      in various tissues in both hamsters and mice; in hamsters, additional
      ultrastructural studies were performed. When administered to hamsters, IPO
      induced moderate to severe cytotoxicity in normal and dysplastic bronchiolar
      lining cells, in most lepidic bronchioloalveolar carcinomas, and in some
      glandular areas of adenosquamous cell carcinomas. Susceptible cells included
      normal, anaplastic, and neoplastic nonciliated and some ciliated bronchiolar
      cells. Undifferentiated and squamous tumor cells were resistant to IPO, as were
      resident normal alveolar type II cells. However, some adenocarcinomas composed
      primarily of ciliated and mucous cells also showed no IPO-induced necrosis,
      indicating a deficiency in appropriate activating enzymes. In the mice, IPO
      induced bronchiolar cell necrosis and, at the high dose, also severe pulmonary
      edema. No cytotoxicity was observed in normal or hyperplastic alveolar
      epithelium, nor in either solid or papillary growth forms of mouse alveolar cell
      tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270608
TI  - Stimulation of prostaglandin E2 production and induction of specific protein
      synthesis in rat peritoneal macrophages by a tumor promoter staurosporine.
AB  - Staurosporine is a microbial anti-fungal alkaloid having potent inhibitory
      activity on protein kinase C and is a non 12-O-tetradecanoylphorbol-13-acetate
      type tumor promoter in two-stage carcinogenesis experiments in mouse skin.
      Effects of staurosporine and its structurally related compounds K-252a, KT5720
      and KT5822 on prostaglandin E2 production, release of arachidonic acid from
      membrane phospholipids, and uptake of [35S]methionine into intracellular proteins
      were examined in rat peritoneal macrophages. Among the four compounds, only
      staurosporine stimulated the production of prostaglandin E2 and release of
      arachidonic acid at concentrations of 1 ng/ml and 10 ng/ml. The uptake of
      [35S]methionine into cellular proteins, estimated to be 120 kDa and 125 kDa
      molecular mass, was also stimulated by staurosporine treatment, and the uptake
      was increased in parallel with the increase in prostaglandin E2 production. At
      higher concentrations (100 ng/ml and 1000 ng/ml), staurosporine inhibited
      prostaglandin E2 production and did not induce the specific protein synthesis.
      Other compounds neither stimulated prostaglandin E2 production nor induced
      specific protein synthesis. K-252a inhibited prostaglandin E2 production at
      concentrations above 10 ng/ml. These results suggest that the staurosporine
      induced proteins might participate in the tumor promotion or at least in the
      staurosporine-induced stimulation of prostaglandin E2 production.

PMID- 8270609
TI  - Chromosome aberrations and cytogenetic intratumor heterogeneity in
      chondrosarcomas.
AB  - Clonal chromosome aberrations identified after short-term culture are presented
      for 13 chondrosarcomas; in 5 cases both the primary tumors and local recurrences
      were studied. The stemline chromosome number was hypodiploid or hyperhaploid in 9
      tumors. The most frequent numerical anomalies were, in falling order of
      frequency, loss of chromosomes Y, 10, 13, and 6, and gain of chromosomes 7 and
      20. No recurrent structural rearrangement was found, but chromosome bands 5q13,
      1q21, 7p11, and 20q11 were each involved in three different rearrangements.
      Karyotypic heterogeneity was assessed in two different ways: as the presence of
      more than one clone in one sample and as the presence of different clones in
      different samples from the same surgical specimen. Clonal karyotypic evolution
      was demonstrated in 6 of the 7 cases in which two or more samples could be
      investigated. All 6 showed intersample heterogeneity. Intrasample heterogeneity
      was found in only 5 of the 28 samples with aberrations. By comparing the
      incidences of the nonrandomly occurring aberrations in stemlines and sidelines in
      the heterogeneous tumors, it was possible to conclude that loss of chromosome 13
      and rearrangement of band 5q13 were early events in the clonal evolution.

PMID- 8270610
TI  - High-affinity chimeric anti-(colorectal carcinoma) antibody correlated to
      enhanced tumor targeting in biodistribution and imaging.
AB  - The genetically engineered chimeric cB72.3m4 and cB72.3m12 antibodies recognize
      the same tumor-associated TAG72 antigen. The high-affinity cB72.3m4 antibody had
      an approximately 18-fold higher affinity constant for the TAG72 antigen than the
      low-affinity cB72.3m12 antibody. The relationship between antibody affinity and
      tumor targeting was studied by using these two antibodies. In biodistribution and
      imaging studies in athymic mice bearing LS174T human colon cancer xenografts, the
      radiolabelled high-affinity cB72.3m4 antibody was rapidly cleared from the blood,
      whereas the low-affinity cB72.3m12 antibody had slower blood clearance. The data
      showed that the high-affinity cB72.3m4 antibody appeared to localize more in
      tumors (based on tumor:normal-tissue ratios) than did the low-affinity cB72.3m12
      antibody, and enhanced the target-to-nontarget image contrast. This study
      provides evidence that the high-affinity chimeric antibody cB72.3m4 may be useful
      in both immunodetection and immunotherapy of cancer.

PMID- 8270611
TI  - Antitumor effects of GBS toxin: a polysaccharide exotoxin from group B beta
      hemolytic streptococcus.
AB  - A group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis
      and respiratory distress ("early-onset disease") produces a polysaccharide
      exotoxin (GBS toxin) that, when infused in sheep, causes lung pathophysiology
      similar to that seen in humans. Histological studies have demonstrated that GBS
      toxin induces a strong inflammatory response in the lung, with pulmonary
      sequestration of granulocytes and extensive capillary endothelial damage. The
      susceptibility of humans to GBS toxin is age-dependent and limited to about 4
      days after birth. It is rarely evident thereafter. This suggests that the binding
      of GBS toxin to the target endothelium occurs via specific components in the
      developing lung endothelial cells of the newborn that are later lost. We report
      here that GBS toxin can also bind to developing endothelium associated with
      neoplasia and induce an inflammatory response. GBS toxin was shown by
      immunohistochemistry to bind to capillary endothelium of human large-cell
      carcinomas. In nude mice bearing human tumor xenografts, intravenously
      administered GBS toxin caused tumor necrosis and hemorrhagic lesions, and
      substantially inhibited the rate of growth of the tumors. In BALB/c mice bearing
      Madison lung tumors, GBS toxin induced an inflammatory response resulting in
      marked changes in tumor morphology, including vasodilation, endothelial and tumor
      cell necrosis, invasion of lymphocytes and macrophages, and capillary thrombosis.
      In these tumor models, no evidence of toxicity to the vasculature of other
      tissues was observed. The reported pathophysiology of GBS in human neonates, the
      lack of disease in non-neonates colonized with GBS, and these results suggest
      that GBS toxin may have potential as a well tolerated agent in cancer therapy of
      some human tumors.

PMID- 8270612
TI  - Persistent proliferation of normal hepatocytes and promotion of preneoplastic
      development by N-nitrosodibenzylamine in rats.
AB  - In a traditional long-term study N-nitrosodibenzylamine (NDBzA) was proven to be
      noncarcinogenic, but recently the substance was found to produce genotoxic
      lesions in hepatocytes. Our own experiments have shown that relatively low single
      doses of NDBzA cause liver hypertrophy and additive proliferation of hepatocytes
      in rats. Both effects are known from well-documented promoters and non-genotoxic
      carcinogens, respectively, in rodents. Investigation of NDBzA in an initiation
      promotion assay (IP assay) showed it to cause an increase in the number and size
      of preneoplastic liver cell foci. This occurred only after initiation with
      diethylnitrosamine, but not when 2-acetylaminofluorene was used. Another property
      of NDBzA is its sustained mitotic stimulation of extrafocal hepatocytes. This is
      inconsistent with their adaptive loss of susceptibility to mitogens in IP assays
      using other promoters of hepatocarcinogenesis. The following conclusions can be
      drawn. First, "differential inhibition" of the proliferation of extrafocal
      hepatocytes, in contrast to the selective mitostimulation of preneoplastic cells,
      is obviously no prerequisite for cancer development. Second, primary mitogenicity
      of a compound in short-term studies can be a useful indicator for tumorigenic
      potential. In the case of NDBzA the data available at present are still
      insufficient to classify it unequivocally in terms of genotoxic or nongenotoxic
      carcinogenicity.

PMID- 8270613
TI  - Digital cell image analysis of verapamil-induced effects in chemosensitive and
      chemoresistant neoplastic cell lines.
AB  - We used chemosensitive and chemoresistant variants of the neoplastic mouse MXT
      mammary and human J82 and T24 bladder cell lines to characterize verapamil
      induced cell proliferation and morphonuclear modifications in drug-treated and
      untreated cells. Chemoresistance to vinorelbine (Navelbine, a Vinca alkaloid
      derivative), to DIAM3 (an investigational alkylating compound) and to Adriamycin
      (an intercalating agent) in the presence or absence of verapamil was monitored by
      means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide assay. The results showed that verapamil restored a significant level of
      chemosensitivity in doses such as 1 microM or 10 microM in the three
      chemoresistant variants. The digital cell image analysis of Feulgen-stained T24
      resistant cell nuclei revealed that verapamil restored the drug-treated cell
      kinetics and morphonuclear features observed in the sensitive counterpart
      especially with respect to the effects of Adriamycin. Interestingly, verapamil
      induced a highly significant chromatin decondensation in resistant but not in
      sensitive variants. Such verapamil-induced decondensation may favour the
      accessibility of drugs to their DNA targets. Therefore, in addition to the well
      known action of the drug on the influx of a cytotoxic compound from the cellular
      to the intracellular compartment, verapamil might also favour the accessibility
      of the nucleus, to the drug.

PMID- 8270614
TI  - Oxygenation of tumors by a hemoglobin solution.
AB  - Tumor oxygen tensions were measured using a computer-controlled PO2
      microelectrode in two preclinical solid tumor models, the rat 9L gliosarcoma and
      the rat 13672 mammary carcinoma. Tumor oxygenation profiles were determined under
      four conditions: (a) during normal air breathing, (b) during carbogen breathing,
      (c) after intravenous administration of a solution of ultrapurified polymerized
      bovine hemoglobin with normal air breathing and (d) after intravenous
      administration of a solution of ultrapurified polymerized bovine hemoglobin with
      carbogen breathing. Both tumors had severely hypoxic regions under normal air
      breathing conditions. Although carbogen breathing increased the oxygenation of
      the better-oxygenated portions of the tumor, it made no impact on the severely
      hypoxic tumor regions. Administration of the hemoglobin solution was effective in
      increasing the oxygenation throughout both tumors under normal air-breathing
      conditions. The addition of carbogen breathing to administration of the
      hemoglobin solution eliminated severe hypoxia in the 9L gliosarcoma and markedly
      reduced the severely hypoxic regions of the 13672 mammary carcinoma. At 24 h
      after administration of the hemoglobin solution the 13672 mammary carcinoma
      showed greater hypoxia than before treatment, which was partially corrected with
      carbogen breathing.

PMID- 8270615
TI  - Comparative studies of cardia carcinoma and infracardial gastric carcinoma.
AB  - In a part retrospective, part prospective study, 354 carcinomas of the cardia
      were compared with 1259 infracardial gastric carcinomas with regard to the age
      and sex of the patients, macroscopic classification, microscopic classifications,
      depth of invasion, and survival rates. Mortality rates are generally higher in
      cardia carcinoma than in stomach carcinoma. The difference is due to the
      significantly poorer survival of cardia carcinoma patients in stage I, while
      mortality rates in stages II, III, and IV of both types are approximately
      similar. Highly significant differences were also found with regard to sex ratio,
      incidence of macro- and microscopic subtypes, and invasive growth. The typical
      cardia carcinoma occurs preferentially in men, is mostly well-delineated, and is
      manifested as an ulcerated or polypoid, well-differentiated tumor of expansive
      growth, corresponding to Lauren's intestinal type. These results confirm the
      concepts of McPeak and Warren, MacDonald, and Siewert et al., that the carcinoma
      located in the cardia must be seen as a separate entity of gastric carcinoma.

PMID- 8270616
TI  - Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma.
AB  - Since the carcinomas of the cardia and the adenocarcinomas of the esophagus show
      many similarities in their histological and morphological descriptions, a
      detailed comparative study was attempted on the basis of 66 esophageal carcinomas
      in adenoid differentiation, 359 carcinomas of the cardia, 1288 gastric carcinomas
      in infracardial localisation, and 492 squamous carcinomas of the esophagus. The
      evaluation yielded no significant differences between the adenocarcinomas of the
      esophagus and the cardia neither in age and sex distribution nor with regard to
      the classifications of Borrmann, WHO, Ming, and Lauren, but a significant
      discrimination was possible between esophageal and cardial adenocarcinoma
      together, on the one hand, and infracardial gastric carcinoma on the other.
      Furthermore, esophageal adenocarcinomas were localized preferentially in the
      lower third, unlike squamous carcinomas of the same organ. These results suggest
      that esophageal adenocarcinoma and carcinoma of the cardia must be considered as
      one separate entity, probably originating from a common stem cell. They further
      suggest that the cardia belongs to the esophagus rather than to the stomach.

PMID- 8270618
TI  - Loss of cytoplasmic basic fibroblast growth factor from physiologically wounded
      myofibers of normal and dystrophic muscle.
AB  - Using muscle as an in vivo model system, we have tested the hypothesis that basic
      fibroblast growth factor is released from a cytoplasmic storage site into the
      extra-cellular environment via diffusion through survivable, mechanically-induced
      plasma membrane disruptions. Normal and dystrophic (mdx) mouse muscle were
      studied. Strong immunostaining for bFGF was detected in the cytoplasm of
      myofibers of uninjured muscle fixed in situ by perfusion. By contrast, myofibers
      did not stain cytoplasmically for bFGF after suffering lethal disruptions of
      their plasma membranes caused by freezing and thawing followed by sectioning. Sub
      lethal, transient disruptions of myofiber plasma membranes--termed plasma
      membrane 'wounds'--were shown to be induced by needle puncture or exercise of
      muscle. Quantitative image analysis revealed that these wounded fibers contained
      significantly reduced levels of bFGF. Dystrophic exercised and unexercised muscle
      was found to possess an approximately 6-fold higher proportion of wounded
      myofibers than does normal muscle under equivalent conditions. Release of bFGF at
      a rate that is a direct function of the frequency of myofiber wounding may
      explain in part how a muscle adjusts its growth to meet changing mechanical
      demand as well as the pathological hypertrophy characteristic of certain stages
      of muscular dystrophy.

PMID- 8270617
TI  - Proadipocyte cell lines: models of cellular proliferation and differentiation.

PMID- 8270619
TI  - The expression of basic fibroblast growth factor and its receptor in cell lines
      derived from normal human mammary gland and a benign mammary lesion.
AB  - mRNA for basic Fibroblast Growth Factor (bFGF) was expressed in a series of SV40
      transformed human mammary cell lines as molecules of 7.1, 3.6, 2.0 and 1.2 kb.
      This expression was much weaker in those lines of epithelial morphology than in
      myoepithelial-like cell lines derived from them. It was confirmed, using northern
      hybridization to single-stranded RNA probes, that the multiple mRNAs were
      transcribed from the coding strand for bFGF. bFGF activity was detected in
      extracts of the cells and the relative amounts of activity corresponded in
      general to the amounts of mRNA found. Similar results were obtained from
      spontaneously transformed cell lines derived from a human benign breast lesion.
      The presence of bFGF protein in the extracts was confirmed by western blotting,
      which showed a band of 18-19 kDa, migrating in the same position as authentic
      bFGF; in addition, the myoepithelial-like cells showed prominent bands of bFGF at
      24 and 26 kDa. No FGF receptor was detectable by the binding of 125I-bFGF to the
      SV40-transformed cell lines or to the epithelial cell lines from the benign
      breast lesion, but both high- and low-affinity receptors were found on
      myoepithelial-like cells derived from the latter. The results indicate that
      differentiation to the human myoepithelial-like phenotype in culture is
      associated with the enhanced expression of bFGF, and it is suggested that bFGF,
      immunocytochemically detected in the basement membrane of the human breast, may
      arise, at least in part, from the myoepithelial cells of the mammary parenchyma.

PMID- 8270620
TI  - Regional variation in distribution of EGF receptor in developing and adult
      corneal epithelium.
AB  - Epidermal growth factor receptor has been localized to the proliferative cell
      layers in a variety of stratified squamous epithelia. In the current study, the
      rat cornea was used as an experimental model to determine if epidermal growth
      factor receptor is concentrated in epithelial stem cells. Epidermal growth factor
      receptor was localized using immunofluorescence microscopy in adult and neonatal
      (1-day to 4-week) rat corneas. Antibody binding to epidermal growth factor
      receptor was present in basal cells across the adult cornea but was more intense
      in the limbal zone. In rats 1 day to 1 week of age, the corneal epithelium
      consisted of one or two layer of cells that were intensely labeled by anti
      epidermal growth factor receptor. Following epithelial stratification, which
      occurred just prior to eyelid opening (approximately 12 days), expression of
      epidermal growth factor receptor was greatly reduced in central corneal
      epithelium and gained an adult pattern by 3 weeks of age. Expression of epidermal
      growth factor receptor was also examined by incubating 1 mm slices of adult
      corneas with 125I-epidermal growth factor (4 nM) for 90 minutes, followed by
      washing and autoradiography. Basal cells in the limbal zone contained 4.5-fold
      more silver grains per cell than did basal cells in the central cornea. These
      data suggest that cells with high potential for proliferation, i.e. limbal basal
      cells and all basal cells in developing rats, express high epidermal growth
      factor receptor levels. High levels of receptor may allow these cells to be
      rapidly stimulated by growth factors to undergo cell division during development
      and following wounding in adult corneas.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270621
TI  - The mouse brown (b) locus protein has dopachrome tautomerase activity and is
      located in lysosomes in transfected fibroblasts.
AB  - Many genes mapping to pigmentation loci are involved in the regulation of melanin
      synthesis in the mouse. The brown (b) locus controls black/brown coat coloration,
      and its product has significant homology to the key melanogenic enzyme
      tyrosinase. This has led to suggestions that the b-protein is itself a
      melanogenic enzyme. In order to investigate its function, we have established
      lines of mouse fibroblasts stably expressing the b-protein by co-transfection of
      a b-protein expression vector and a plasmid conferring resistance to the
      antibiotic G418. The b-protein synthesised by these cells has the expected
      molecular mass of 75 kDa and reacts with three different anti-b-protein
      antibodies. We were unable to confirm previous reports that the b-protein has
      tyrosinase or catalase activity, but detected stereospecific dopachrome
      tautomerase activity in b-protein-expressing fibroblasts. This dopachrome
      tautomerase binds to Concanavalin A-Sepharose, and the major product of its
      action on L-dopachrome is 5,6-dihydroxyindole-2-carboxylic acid. Since this
      activity is not present in untransfected cells we conclude that the b-protein has
      dopachrome tautomerase activity. Fibroblasts do not contain melanosomes, the
      specialised organelles in which the b-protein is located in melanocytes.
      Nevertheless, indirect immunofluorescence localisation of the b-protein in
      transfected fibroblasts produces a distinctive pattern of intense juxtanuclear
      staining combined with punctate cytoplasmic staining. Double-labelling shows co
      localisation of the b-protein with the late endosomal/lysosomal markers beta
      glucuronidase and LAMP-1, both in transfected fibroblasts and in mouse melanoma
      cells. These findings are consistent with the hypothesis that melanosomes are
      closely related to lysosomes.

PMID- 8270622
TI  - Synthesis and assembly of fibrillin by fibroblasts and smooth muscle cells.
AB  - The expression and assembly of the microfibrillar glycoprotein fibrillin has been
      investigated in cultures of nuchal ligament fibroblasts, skin fibroblasts and
      vascular smooth muscle cells. The level of fibrillin expression varied with the
      cell type and growth conditions. Higher levels of synthesis were recorded in
      quiescent post-confluent cells than in actively dividing subconfluent cultures.
      Nuchal ligament fibroblasts consistently synthesized the highest levels of
      fibrillin. Growth of cells in the presence of ascorbate resulted in an increased
      proportion of newly synthesized fibrillin retained within cell layers. Fibrillin
      was immunoprecipitated from medium and cell layer extracts in the form of
      monomers and high-M(r) disulphide-bonded aggregates. Rotary shadowing electron
      microscopy of cell layer extracts and collagen gels provided direct evidence for
      the assembly of extensive intact microfibrils by smooth muscle cells and
      fibroblast cultures. Gel filtration chromatography of medium and cell layer
      extracts, in combination with immunoprecipitation of column fractions, provided a
      means of analysing the size distribution and assembly of newly synthesized
      fibrillin. This cell culture approach provides an opportunity to evaluate normal
      and aberrant synthesis and assembly of fibrillin in a wide range of cell types.

PMID- 8270623
TI  - In vivo observation of the puff-specific protein no-on transient A (NONA) in
      nuclei of Drosophila embryos.
AB  - The spatial distribution of no-on transient A (NONA), a protein associated with
      specific puffs on polytene chromosomes, was followed in nuclei of living
      Drosophila embryos by microinjection of fluorescently labeled monoclonal antibody
      to NONA. The injected antibodies remained active until the larval stage,
      revealing the distribution of the NONA protein throughout embryogenesis. Most
      injected animals completed embryonic development and hatched as normal larvae.
      NONA was restricted to the cytoplasm until the end of cycle 11. We document an
      active uptake of the NONA-antibody complex into early interphase nuclei from
      nuclear cycle 14 onwards, following each mitosis. Significant differences in the
      distribution of the protein between fixed and living embryos were apparent,
      particularly at high resolution. The NONA protein was localized in the nuclei of
      living embryos at discrete sites, most of which lay at the periphery and some of
      which were tightly clustered. The constellation of sites changed with time; in
      some nuclei these changes were fast whereas in other nuclei the pattern was quite
      stable. These data suggest that specific protein complexes associated with active
      interphase chromatin, and possibly chromatin in general, are mobile in the living
      organism.

PMID- 8270624
TI  - Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the
      interdigital tissue of the embryonic chick leg bud.
AB  - In this work we have attempted to characterize the programmed cell death process
      in the chick embryonic interdigital tissue. Interdigital cell death is a
      prominent phenomenon during limb development and has the role of sculpturing the
      digits. Morphological changes in the regressing interdigital tissue studied by
      light, transmission and scanning electron microscopy were correlated with the
      occurrence of internucleosomal DNA fragmentation, evaluated using agarose gels.
      Programming of the cell death process was also analyzed by testing the
      chondrogenic potential of the interdigital mesenchyme, in high density cultures.
      Our results reveal a progressive loss of the chondrogenic potential of the
      interdigital mesenchyme, detectable 36 hours before the onset of the degenerative
      process. Internucleosomal DNA fragmentation was only detected concomitant with
      the appearance of cells dying with the morphology of apoptosis, but unspecific
      DNA fragmentation was also present at the same time. This unspecific DNA
      fragmentation was explained by a precocious activation of the phagocytic removal
      of the dying cells, confirmed in the tissue sections. From our observations it is
      suggested that programming of cell death involves changes before endonuclease
      activation. Further, cell surface changes involved in the phagocytic uptake of
      the dying cells appear to be as precocious as endonuclease activation.

PMID- 8270625
TI  - Identification of rat epidermal profilaggrin phosphatase as a member of the
      protein phosphatase 2A family.
AB  - The aggregation of cellular intermediate filaments is an important step in the
      terminal differentiation of keratinocytes. It has been shown that epidermal
      filaggrin can cause intermediate filaments to aggregate in vitro and may also
      have the same function in vivo. Filaggrin is derived via dephosphorylation and
      proteolysis from a highly phosphorylated precursor, profilaggrin, which is found
      in the granular layer of the epidermis. Using casein kinase II phosphorylated
      filaggrin as substrate, a profilaggrin phosphatase has been partially purified
      from rat epidermal homogenate by three chromatographic steps (DE52,
      hydroxylapatite and S200 gel filtration). Profilaggrin phosphatase activity
      eluted from the last column has a Km of 0.12 mM and a Vmax of 8 nmol/mg/min with
      respect to phosphofilaggrin. Results obtained by initial rate analysis showed
      that the enzymatic activity is not affected by phospho-tyrosyl phosphatase
      inhibitors and the active fractions preferentially dephosphorylate the alpha
      subunit of phosphorylase kinase which has been phosphorylated by cAMP-dependent
      kinase. These results suggest that epidermal profilaggrin phosphatase is not a
      phospho-tyrosyl phosphatase or a type 1 phospho-seryl/phospho-threonyl
      phosphatase. Dephosphorylation is not affected by EDTA, calcium or magnesium, but
      is very sensitive to okadaic acid inhibition (IC50 = 80 pM), suggesting that the
      enzymatic activity is related to that of the protein phosphatase 2A
      (PP2A).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270626
TI  - Multiple structural types of gap junctions in mouse lens.
AB  - Gap junctions in the epithelium and superficial fiber cells from young mice were
      examined in lenses prepared by rapid-freezing, and processed for freeze
      substitution and freeze-fracture electron microscopy. There appeared to be three
      structural types of gap junction: one type between epithelial cells and two types
      between fiber cells. Epithelial gap junctions seen by freeze-substitution were
      approximately 20 nm thick and consistently associated with layers of dense
      material lying along both cytoplasmic surfaces. Fiber gap junctions, in contrast,
      were 15-16 nm (type 1) or 17-18 nm thick (type 2), and had little associated
      cytoplasmic material. Type 1 fiber gap junctions were extensive in flat expanses
      of cell membrane and had a thin, discontinuous central lamina, whereas type 2
      fiber gap junctions were associated with the ball-and-socket domains and
      exhibited a dense, continuous central lamina. Both types of fiber gap junction
      had a diffuse arrangement of junctional intramembrane particles, whereas
      particles and pits of epithelial gap junctions were in a tight, hexagonal
      configuration. The type 2 fiber gap junctions, however, had a larger particle
      size (approximately 9 nm) than the type 1 (approximately 7.5 nm). In addition, a
      large number of junctional particles typified the E-faces of both fiber types but
      not the epithelial type of gap junction. Gap junctions between fiber and
      epithelial cells had structural features of type 1 fiber gap junctions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8270627
TI  - Evidence that vault ribonucleoprotein particles localize to the nuclear pore
      complex.
AB  - Vaults are cytoplasmic ribonucleoprotein organelles that are highly conserved
      among diverse eukaryotic species. Their mass (12.9 MDa), diameter (26-35 nm) and
      shape (two halves, each with eightfold radial symmetry) have recently been
      determined and are similar to those ascribed to the central plug (or transporter)
      of the nuclear pore complex (NPC). The size and eightfold symmetry of the vault
      particle make it conducive to interacting physically in a complementary manner
      with NPCs. The present study demonstrates that vaults specifically associate with
      nuclei by both immunoblotting and immunofluorescence. Immunogold EM confirmed
      that vaults associate with the nuclear envelope in tissue sections and with NPCs
      of isolated nuclei.

PMID- 8270628
TI  - The origin of parasitophorous vacuole membrane lipids in malaria-infected
      erythrocytes.
AB  - During invasion of an erythrocyte by a malaria merozoite, an indentation develops
      in the erythrocyte surface at the point of contact between the two cells. This
      indentation deepens as invasion progresses, until the merozoite is completely
      surrounded by a membrane known as the parasitophorous vacuole membrane (PVM). We
      incorporated fluorescent lipophilic probes and phospholipid analogs into the
      erythrocyte membrane, and followed the fate of these probes during PVM formation
      with low-light-level video fluorescence microscopy. The concentration of probe in
      the forming PVM was indistinguishable from the concentration of probe in the
      erythrocyte membrane, suggesting that the lipids of the PVM are continuous with
      and derived from the host cell membrane during invasion. In contrast,
      fluorescently labeled erythrocyte surface proteins were largely excluded from the
      forming PVM. These data are consistent with a model for PVM formation in which
      the merozoite induces a localized invagination in the erythrocyte lipid bilayer,
      concomitant with a localized restructuring of the host cell cytoskeleton.

PMID- 8270629
TI  - A model system for studying membrane biogenesis. Overexpression of cytochrome b5
      in yeast results in marked proliferation of the intracellular membrane.
AB  - Cytochrome b5 is an amphipathic microsomal protein that is anchored to the
      endoplasmic reticulum by a single hydrophobic transmembrane alpha-helix located
      near the carboxyl terminus of the protein. In yeast, cytochrome b5 provides
      electrons for fatty acid desaturation and ergosterol biosynthesis. High level
      expression of cytochrome b5 in Saccharomyces cerevisiae was achieved using the
      yeast metallothionein promoter and a synthetic cytochrome b5 gene. In order to
      accommodate the markedly increased amount of the membrane-bound cytochrome b5,
      the yeast cell proliferated its nuclear membrane. As many as 20 pairs of stacked
      membranes could be observed to partially encircle the nucleus. This morphological
      arrangement of membrane around the nucleus is known as a karmella. In an effort
      to understand which part of the cytochrome b5 molecule, i.e. the membrane anchor
      or the soluble heme domain, which is competent in electron transfer, provided the
      signal for the de novo membrane biogenesis, a series of studies, including site
      directed mutagenesis, was undertaken. The results of these experiments
      demonstrated that the inactive hemedeficient apo form of the membrane-bound
      protein stimulates membrane proliferation to the same extent as the holo wild
      type protein, whereas cytosolic forms of cytochrome b5 did not induce membrane
      synthesis. These data demonstrate that membrane proliferation is a consequence of
      the cell's ability to monitor the level of membrane proteins and to compensate
      for alterations in these levels rather than the result of the ability of the
      extra cytochrome b5 to catalyze synthesis of extra lipid that had to be
      accommodated in new membrane. Site-directed mutagenesis studies of the membrane
      binding domain of cytochrome b5 provided additional clues about the nature of the
      signal for membrane proliferation. Replacement of the membrane anchor by a non
      physiological nonsense sequence of 22 leucines gave rise to a mutant protein that
      triggered membrane biosynthesis. The conclusion from these experiments is clear;
      the signal for membrane proliferation does not reside in some specific amino acid
      sequence but instead in the hydrophobic properties of the proliferant.
      Interestingly, these membranes are somewhat diminished in quantity and have a
      slightly altered morphology compared to those induced by the wild-type protein.
      It was also observed that disruption of the putative alpha helix of the membrane
      anchor by an Ala116Pro mutation, which gives rise to two sequential prolines at
      positions 115 and 116 results in a protein with diminished capacity to induce
      membrane formation.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270630
TI  - The nuclear pore complex: three-dimensional surface structure revealed by field
      emission, in-lens scanning electron microscopy, with underlying structure
      uncovered by proteolysis.
AB  - The structure of the nuclear pore complex (NPC) has been previously studied by
      many different electron microscopic techniques. Recently, scanning electron
      microscopes have been developed that can visualise biologically relevant
      structural detail at the same level of resolution as transmission electron
      microscopes and have been used to study NPC structure. We have used such an
      instrument to visualise directly the structure of both cytoplasmic and
      nucleoplasmic surfaces of the NPC of manually isolated amphibian oocyte nuclear
      envelopes that have been spread, fixed, critical point dried and coated with a
      thin fine-grained film of chromium or tantalum. We present images that directly
      show features of the NPC that are visible at each surface, including coaxial
      rings, cytoplasmic particles, plug/spoke complexes and the nucleoplasmic basket
      or fishtrap. Some cytoplasmic particles are rod-shaped or possibly "T"-shaped,
      can be quite long structures extending into the cytoplasm and may be joined to
      the coaxial ring at a position between each subunit. Both coaxial rings, which
      are proud of the membranes, can be exposed by light proteolytic digestion,
      revealing eight equal subunits each of which may be bipartite. We have determined
      that the nucleoplasmic filaments that make up the baskets are attached to the
      outer periphery of the coaxial ring at a position between each of its subunits.
      These filaments extend into the nucleoplasm and insert at the distal end to the
      smaller basket ring. The space left between adjacent basket filaments would
      exclude particles bigger than about 25 nm, which is consistent with the exclusion
      limit previously found for NPC-transported molecules.

PMID- 8270631
TI  - Prp20, the Saccharomyces cerevisiae homolog of the regulator of chromosome
      condensation, RCC1, interacts with double-stranded DNA through a multi-component
      complex containing GTP-binding proteins.
AB  - Prp20, a homolog to the mammalian negative regulator of chromosome condensation,
      RCC1, is retained on double-stranded (ds) DNA-cellulose when extracts are
      prepared from asynchronously growing wild-type yeast strains. Conversely, neither
      Prp20 from ts mutant cell extracts nor wt yeast Prp20 produced in Escherichia
      coli, bind to dsDNA-cellulose. In vitro reconstitution assays using E. coli
      expressed Prp20 and inactivated ts mutant extracts of prp20-1 reveal that the
      Prp20 protein requires the assistance of other proteins in the cell extract to
      promote its binding to dsDNA. Immunoprecipitations and sizing-column
      chromatography indicate that the Prp20 protein binds to the dsDNA column through
      a multicomponent complex composed of six to seven proteins, which has a
      collective molecular mass greater than 150,000 Da. At least three of the members
      of this Prp20 complex will bind GTP in vitro. Moreover, the Prp20 complex is
      shown to specifically lose its ability to bind dsDNA during the DNA replication
      phase of the cell cycle. This loss of dsDNA binding during the S phase of the
      cell cycle does not affect the proper organization of the nucleoplasm and appears
      to be reversed before the cell enters mitosis.

PMID- 8270632
TI  - Selective killing induced by an inhibitor of N-linked glycosylation.
AB  - Treatment with a low dose (0.5 microgram/ml) of tunicamycin (an inhibitor of N
      linked glycosylation) blocked the cell cycle progression of both normal Balb/c
      3T3 cells (A31) and their SV40-transformed derivatives (SVA31) specifically in
      early G1 (0-3 h after mitosis). Upon release after an 8-h treatment the A31 cells
      returned to the cell cycle via a 9-h recovery phase, indicating that they were
      arrested in G0. The A31 cells were fully viable after this treatment. In
      contrast, the postmitotic SVA31 cells, which were unable to arrest in G0, did not
      divide after the removal of tunicamycin. Instead, these cells died but this did
      not occur until 22-34 h after release from the treatment. SVA31 cells that had
      passed the postmitotic phase of G1 survived during the parental generation and
      divided normally. However, a large portion of these cells died during the next
      cycle, and in total during a 48-h period approximately 50% of the cells were
      killed as a consequence of an 8-h exposure to tunicamycin. In contrast, treatment
      with inhibitors of protein synthesis and HMG CoA reductase activity as well as
      inhibitors of modification of N-linked oligosaccharide chains did not result in
      cell death.

PMID- 8270633
TI  - Menadione-induced oxidative stress leads to a rapid down-modulation of
      transferrin receptor recycling.
AB  - It has been demonstrated that perturbation of oxidative balance plays an
      important role in numerous pathological states as well as in physiological
      modifications leading to aging. In order to evaluate the role of the oxidative
      state in cells, biochemical and ultrastructural studies were carried out on K562
      and HL-60 cell cultures. Particular attention was given to the transferrin
      receptor, which plays an important role in cellular iron metabolism. In order to
      evaluate if oxidative stress influences the transferrin receptor regulation
      process, the free-radical inducer menadione was used. The results obtained seem
      to indicate that oxidative stress is capable of inducing a rapid and specific
      down-modulation of the membrane transferrin receptor due to a block of receptor
      recycling on the cell surface, without affecting ligand-binding affinity. These
      effects were observed in the early stages of menadione treatment and before any
      typical signs of subcellular damage, including surface blebbing, a well-known
      cytopathological marker of menadione-induced injury. The mechanisms underlying
      such phenomena appear to be related to cytoskeletal protein thiol group oxidation
      as well as to the perturbation of calcium homeostasis, both induced by menadione.
      It is thus hypothesized that the data reported here represent a specific example
      of a general mechanism by which cell surface receptor expression and recycling
      can be influenced by oxidative balance.

PMID- 8270634
TI  - Molecular cloning of a 47 kDa tissue-specific and differentiation-dependent
      urothelial cell surface glycoprotein.
AB  - Despite the fact that bladder epithelium has many interesting biological features
      and is a frequent site of carcinoma formation, relatively little is known about
      its biochemical differentiation. We have shown recently that a 47 kDa
      glycoprotein, uroplakin III (UPIII), in conjunction with uroplakins I (27 kDa)
      and II (15 kDa), forms the asymmetric unit membrane (AUM)--a highly specialized
      biomembrane characteristic of the apical surface of bladder epithelium.
      Deglycosylation and cDNA sequencing revealed that UPIII contains up to 20 kDa of
      N-linked sugars attached to a core protein of 28.9 kDa. The presence of an N
      terminal signal peptide sequence and a single transmembrane domain located near
      the C terminus, plus the N-terminal location of all the potential N-glycosylation
      sites, points to a type I (N-exo/C-cyto) configuration. Thus the mass of the
      extracellular domain (20 kDa plus up to 20 kDa of sugar) of UPIII greatly exceeds
      that of its intracellular domain (5 kDa). Such an asymmetrical mass distribution,
      a feature shared by the other two major uroplakins, provides a molecular
      explanation as to why the luminal leaflet of AUM is almost twice as thick as the
      cytoplasmic one. The fact that of the three major proteins of AUM only UPIII has
      a significant cytoplasmic domain suggests that this molecule may play an
      important role in AUM-cytoskeleton interaction in terminally differentiated
      urothelial cells.

PMID- 8270635
TI  - In vivo expression and molecular characterization of the porcine slow-myosin
      heavy chain.
AB  - We report on the molecular characterization of the porcine slow-myosin heavy
      chain (HC) beta gene and the isolation of its 5' end cDNA. In vivo expression
      study, by in situ hybridization and histochemistry, revealed a highly regular
      rosette pattern of fiber arrangement, with a slow fiber occupying the central
      core, in all the skeletal muscles examined. This feature can be advantageous in
      the distinction of primary and secondary fibers in myogenic lineage studies. In
      the neonatal heart, beta isoform expression is diffuse, with higher expression
      occurring in the ventricle than in the atrium. Transient transfection assays
      showed the porcine promoter functions in a muscle- and differentiation stage
      specific manner. In the 5' regulatory region are several putative positive and
      negative regulatory elements, including a positive and a negative element in
      close proximity to each other in intron 1.

PMID- 8270636
TI  - The sequence of alignment of microtubules, focal contacts and actin filaments in
      fibroblasts spreading on smooth and grooved titanium substrata.
AB  - Contact guidance refers to the reactions of cells with the topography of their
      substratum. Current hypotheses on the mechanism of contact guidance focus on the
      dynamic behaviour of the cytoskeletal components, but most observations have been
      made on cells that have already become oriented with topographic features of the
      substratum. The purpose of this study was to examine the sequence in which
      microtubules, focal contacts and microfilament bundles become aligned to the
      substratum topography as fibroblasts spread on grooved substrata. Human gingival
      fibroblasts were trypsinized and seeded onto grooved titanium surfaces produced
      by micromachining, as well as onto control smooth surfaces. After observation and
      photography of the spreading cells at times up to 6 hours, the cells were fixed
      and exposed to one or more of the following antibodies or fluorescent stains:
      phallacidin to stain actin filaments, monoclonal anti-tubulin, monoclonal anti
      vinculin, anti-mouse IgG labelled with Texas-Red or FITC, and/or an aldehyde
      reactive stain to identify the cell outline. The cells were photographed and cell
      area, shape and orientation were calculated. Cells were also examined with
      confocal microscopy to obtain optical sections so that cell height as well as the
      precise locations of the cytoskeletal components with respect to the vertical
      dimension of the grooved substrata could be determined. Microtubules were the
      first element to become oriented parallel to the direction of the grooves and
      were first aligned at the bottom of the grooves. This alignment of microtubules
      was evident as early as 20 minutes after plating and preceded the orientation of
      the cell as a whole. Aligned actin microfilament bundles were not observed until
      40-60 minutes and were observed first at the wall-ridge edges. At early times,
      focal contacts were distributed radially, but only after 3 hours did the majority
      of cells demonstrate aligned focal contacts. If the first cytoskeletal component
      to become aligned is the prime determinant of cell orientation, then these data
      suggest that microtubules in human gingival fibroblasts may determine cell
      orientation on grooved titanium surfaces. By analogy with microtubule behaviour
      in other systems, we suggest that microtubule orientation on grooved substrata
      may occur as a result of the substratum establishing shear-free planes.

PMID- 8270637
TI  - Adhesion of CHO cells to fibronectin is mediated by functionally and structurally
      distinct adhesion plaques.
AB  - We have investigated the dynamics between free fibronectin receptors and clusters
      of them organized into adhesion plaques on CHO cells using the ability of these
      free integrins to be endocytosed and recycled to the plasma membrane. Indirect
      inhibition of the endocytic cycle by monensin resulted in the subsequent
      internalization of free receptors, which we followed by indirect immunostaining
      and confocal microscopy. Consequently, all the adhesive structures that were in
      equilibrium with free integrins became progressively disorganized. The cellular
      morphological changes were analyzed and correlated with the distribution of cell
      substratum contacts viewed by confocal images obtained after immunostaining with
      antibodies raised against the fibronectin receptor, talin, vinculin and actin.
      After cell adhesion to fibronectin, blockage of the endocytic cycle induced
      disruption of the adhesion plaques that were mainly localized at the cell
      periphery, and disappearance of the stress fibers. However, the cells remained
      firmly attached to the substratum through focal contacts localized in the central
      part of the cell. These central focal contacts, but not the peripheral adhesion
      plaques, could form when the vesicular traffic was blocked prior to adhesion and
      they allowed the cells to attach and flatten onto the substratum. Whereas both
      adhesive structures contained the same receptors linked to talin and vinculin,
      the central adhesive structures were attached to a short stretch of actin but
      never permitted the organization of stress fibers.

PMID- 8270638
TI  - Cell binding specificity of mouse R-cadherin and chromosomal mapping of the gene.
AB  - R-cadherin was originally identified as a chicken cadherin expressed by the
      retina. Here, we describe the identification of a mouse homologue of R-cadherin.
      We isolated mouse cDNAs encoding a cadherin with 94% identity in amino acid
      sequence to the chicken R-cadherin, and defined this molecule as mouse R
      cadherin. L cells transfected with the mouse R-cadherin cDNA acquired a cadherin
      mediated cell-cell adhesiveness as found for other cadherins. To examine the
      binding specificity of mouse R-cadherin, L cells expressing this cadherin (mRL)
      were mixed with L cells expressing chicken R-cadherin (cRL), mouse N-cadherin
      (mNL), mouse E-cadherin (mEL) and mouse P-cadherin (mPL). While mRL cells
      randomly intermixed with cRL cells, those cells aggregated separately from mEL or
      mPL cells. Mixing of mRL with mNL cells gave an intermediate result; that is,
      they formed both separate and chimeric aggregates, suggesting that R- and N
      cadherin can interact with each other although each has a preference to bind to
      its own type. Similar properties were previously found for chicken R-cadherin.
      Thus, the cell binding specificity of R-cadherin is entirely conserved between
      the two species, suggesting a conserved role for this protein in morphogenesis.
      We also located the mouse R-cadherin gene to chromosome 2.

PMID- 8270639
TI  - Acidosomes: recipients of multiple sources of membrane and cargo during
      development and maturation.
AB  - Acidosomes are organelles that in Paramecium are responsible for the
      acidification of phagosomes before phagosomes fuse with lysosomes. Using a
      combination of (a) the quick-freeze deep-etch (QF-DE) technique, (b) monoclonal
      antibodies (mAbs) that label specific membrane pools including those of the
      acidosomes, and (c) horseradish peroxidase (HRP)-uptake studies, we followed the
      development of acidosomes from the Golgi complex as well as the rapid transfer of
      HRP into the acidosomes. We also studied some of the characteristics of the
      involved membrane pools. Morphologically, acidosomes were first detected in the
      cytosol near the ER and Golgi stacks as clumps of tubules and vesicles, which
      apparently coalesced to form larger spherical or elongated preacidosomes. These
      clumped vesicles and preacidosomes had a QF-DE morphology resembling that of the
      mature acidosomes and were specifically labeled with mAbs that also labeled
      mature acidosomes. Within 10 s HRP cargo could be internalized by acidosomes
      while they were docked at the nascent vacuole membrane. This rapid uptake of HRP
      along with membrane occurs by vesicle fusion, a conclusion supported by QF-DE
      images. Thus the acidosome obtains its membrane from at least two sources, from
      the trans-Golgi network, and from the small HRP-containing vesicles. Cargo can
      also be acquired from two sources, the Golgi apparatus and the transport
      vesicles. Since it acquires non-particulate exogenous marker we conclude that the
      acidosome is linked to the endocytic pathway.

PMID- 8270640
TI  - Endocytosis of folate-protein conjugates: ultrastructural localization in KB
      cells.
AB  - It has been demonstrated that proteins covalently conjugated to folic acid may be
      taken up by cells via endocytosis after binding to a folate binding protein (FBP)
      in the cell membrane. The proteins taken up in this manner remain catalytically
      active and they may modify physiological processes occurring in the cytosol.
      Confocal fluorescence microscopy of KB cells incubated with FITC-bovine serum
      albumin-folic acid conjugates showed that after uptake, the conjugates resided in
      large vesicular structures. The purpose of the present study was to determine the
      subcellular localization of protein-folic acid conjugates in KB cells using folic
      acid-bovine serum albumin-colloidal gold (F-BSA-CG) as a tracer. F-BSA-CG
      conjugates were taken up via uncoated pits or caveolae, and resided primarily in
      multivesicular bodies (MVBs) and other tubular endosomes at early time points (15
      60 min). At later time points (6 hours), conjugates were still contained in MVBs
      but some were also found in secondary lysosomes or free in the cytoplasm.
      Coincubation of KB cells with transferrin-colloidal gold (TF-CG) and F-BSA-CG
      resulted in colocalization of TF-CG and F-BSA-CG within endosomal elements at
      times later than 15 minutes, indicating that the caveolae-mediated F-BSA-CG
      endocytic pathway converged with a pathway utilized by clathrin-coated pits.

PMID- 8270641
TI  - Immunological characterization of lamins in the nuclear matrix of onion cells.
AB  - We have used polyclonal and monoclonal antibodies against different lamins from
      vertebrates, and the IFA antibody recognizing all kinds of intermediate filament
      proteins, to investigate the lamins of the nuclear matrix of Allium cepa
      meristematic root cells. All the antibodies react in the onion nuclear matrix
      with bands in the range of 60-65 kDa, which are enriched in the nuclear matrix
      after urea extraction, and do not crossreact with other antibodies recognizing
      intermediate filaments in plants (AFB, anti-vimentin and MAC 322), ruling out
      crossreaction with contaminating intermediate filaments of cytoplasmic bundles.
      In 2-D blots the chicken anti-lamin serum reacts with one spot at 65 kDa and pI
      6.8 and the anti B-type lamin antibodies with another one at 64 kDa and pI 5.75.
      Both crossreact with IFA. The lamin is localized at the nuclear periphery and the
      lamina by indirect immunofluorescence. Immunogold labelling of nuclear matrix
      sections reveals that the protein is not only associated with the lamina, but
      also with the internal matrix. Taken together these results reveal that higher
      plants, which do not possess an organized network of cytoplasmic intermediate
      filaments, nevertheless present a well-organized lamina containing lamins in
      which at least one of them is immunologically related to vertebrate lamin B. Our
      data confirm that lamins are very old members of the intermediate filament
      proteins that have been better conserved in plants during evolution than their
      cytoplasmic counterparts.

PMID- 8270642
TI  - Differential expression of plasminogen activators and their inhibitors in an
      organotypic skin coculture system.
AB  - Using immunohistochemistry and in situ hybridization, we have characterized the
      expression and localization of components of the plasminogen activator
      proteolytic cascade in an organotypic coculture system which consists of a
      "dermal" portion (human dermal fibroblasts throughout a collagen matrix) and a
      stratified, well-differentiated epidermal portion. Specifically, the following
      components were examined: the enzymes urokinase-type plasminogen activator and
      tissue-type plasminogen activator and their type 1 and type 2 inhibitors.
      Urokinase plasminogen activator mRNA and antigen were found predominantly in the
      least differentiated, basal keratinocytes; in some fields there was also faint
      deposition of antigen beneath the basal cells. The distribution of plasminogen
      activator inhibitor type 1 was similar to that of urokinase, except that
      inhibitor type 1 antigen deposition beneath the basal cells appeared more intense
      and uniform. In contrast to the results with urokinase plasminogen activator and
      inhibitor type 1, tissue plasminogen activator mRNA and antigen were localized
      focally in the suprabasal, i.e. more differentiated, keratinocytes. Plasminogen
      activator inhibitor type 2 mRNA and antigen were detected in most epidermal
      layers, but were more intense suprabasally and often spared the basal layer.
      These studies demonstrate that the same type of cell, i.e. the keratinocyte, can
      express different components of the plasminogen activator cascade depending on
      its state of differentiation. The change in expression of plasminogen activator
      cascade components with keratinocyte differentiation suggests distinct epidermal
      functions for these components, related to cell-matrix interaction and epidermal
      differentiation.

PMID- 8270643
TI  - Selective distributions of proteoglycans and their ligands in pericellular matrix
      of cultured fibroblasts. Implications for their roles in cell-substratum
      adhesion.
AB  - We showed previously that a large chondroitin sulfate proteoglycan, PG-M (also
      known as versican), inhibits cell-substratum adhesion, while basement membrane
      heparan sulfate proteoglycan (recently named perlecan) does not (Yamagata et al.
      (1989) J. Biol. Chem. 264, 8012-8018). To extend our understanding of the
      adhesive function of these proteoglycans, we examined the pericellular
      localization of the proteoglycans and their ligands and also that of some matrix
      receptors and cytoskeletal molecules in various fibroblast culture systems. PG-M
      was abundant in the subcellular space of fibroblasts, but was excluded
      selectively from focal contacts where vinculin, integrins and fibronectin were
      localized. Hyaluronan, CD44 and tenascin were distributed similarly as PG-M. In
      contrast, perlecan was associated with fibronectin and was included in focal
      contacts. Syndecan-1, a membrane heparan sulfate/chondroitin sulfate
      proteoglycan, was associated with fibronectin at the cell surface, partly at
      focal contacts and in association with stress fibers. Thus, complexes of PG-M
      with hyaluronan, tenascin and CD44, are not involved in focal contacts. On the
      other hand, perlecan and syndecan-1 together with fibronectin may participate in
      focal contacts. The difference in localization between these proteoglycans may be
      related to their glycosaminoglycan content and to their distinctive roles in cell
      substratum adhesion.

PMID- 8270644
TI  - The 270 kDa splice variant of erythrocyte beta-spectrin (beta I sigma 2)
      segregates in vivo and in vitro to specific domains of cerebellar neurons.
AB  - Spectrin isoforms arise from four distinct genes, three of which generate
      multiple alternative transcripts. With no biochemical restrictions on the
      assembly of alpha beta heterodimers, more than 25 distinct heterodimeric spectrin
      species may exist. Whether (and why) this subtle but substantial diversity is
      realized in any single cell is unknown. To address this question, sequence
      specific antibodies to alternatively spliced regions of alpha- and beta-spectrin
      have been prepared. Reported here is the localization in rat cerebellar neurons
      at light and electron microscopic levels of an antibody against a unique sequence
      (beta I sigma 2-A = PGQHKDGQKSTGDERPT) from the 270 kDa transcript of the red
      cell beta-spectrin gene (spectrin beta I sigma 2). In this version, the 3'
      sequence of erythroid beta-spectrin (beta I sigma 1) is replaced with an
      alternative sequence that shares substantial homology with the 3' sequence of non
      erythroid beta-spectrin (beta II sigma 1). The antibody to beta I sigma 2-A
      stains a single protein band at 270 kDa, determined by western blotting, in both
      rat cerebellum and in cultured cerebellar granule cells, and does not react with
      beta II sigma 1 spectrin (beta-fodrin). This antibody stains the dendritic spines
      of Purkinje cells in the molecular layer, and is concentrated at postsynaptic
      densities (PSDs) adjacent to synapsin I (which is confined to the presynaptic
      membrane). The soma of Purkinje cells do not stain. In the granular layer,
      cytoplasmic organelles and the postsynaptic densities of granular cells stain
      strongly. Astrocytes are also stained. In all cells, plasma membrane staining is
      confined to postsynaptic densities (PSD). The beta I sigma 2 isoform co
      immunoprecipitates with non-erythroid alpha-spectrin (alpha II sigma), even
      though the distribution of alpha II sigma within neurons only partially overlaps
      that of beta I sigma 2. No hybrid beta I sigma 2 and beta II sigma 1 (beta
      fodrin) spectrin complexes appear to exist. Spectrin beta I sigma 2 is also
      polarized in cultured rat cerebellar granule cells, where it is abundant in cell
      bodies but not neurites. The overall distribution of beta I sigma 2 is as a
      subset of the distribution of spectrins 240/235E previously detected with a
      generally reactive erythrocyte alpha beta-spectrin antibody. These findings
      establish the highly precise segregation of a beta-spectrin isoform to distinct
      cytoplasmic and membrane surface domains, indicate that it is complexed
      (partially) with non-erythroid alpha-spectrin, and demonstrate that cytoskeletal
      targeting mechanisms are preserved in cultured granular cells.(ABSTRACT TRUNCATED
      AT 400 WORDS)

PMID- 8270645
TI  - Novel structural organisation of a Mus musculus DBA/2 chromosome shows a fixed
      position for the centromere.
AB  - Chromosome 1 of the inbred mouse strain DBA/2 shows an unusual polymorphism
      associated with its centromeric satellite DNA sequences. The minor satellite
      array has undergone amplification and is present as two blocks separated by major
      satellite sequences. Both minor satellite blocks appear to carry the sequence
      motif necessary for CENP-B protein binding. Despite this apparent similarity the
      functional centromere, as defined by the location of CREST antigens, appears to
      form only within the more terminal block. The two blocks also vary in that sister
      chromatid association only occurs with this more terminal block.

PMID- 8270646
TI  - Mutations in the Drosophila melanogaster gene three rows permit aspects of
      mitosis to continue in the absence of chromatid segregation.
AB  - We have cloned the three rows (thr) gene, by a combination of chromosome
      microdissection and P element tagging. We describe phenotypes of embryos
      homozygous for mutations at the thr locus. Maternal mRNA and protein appear to be
      sufficient to allow 14 rounds of mitosis in embryos homozygous for thr mutations.
      However, a small percentage of cells in syncytial blastoderm stage thr embryos
      sink into the interior of the embryo as if they have failed to divide properly.
      Following cellularisation all cells complete mitosis 14 normally. All cells
      become delayed at mitosis 15 with their chromosomes remaining aligned on the
      spindle in a metaphase-like configuration, even though both cyclins A and B have
      both been degraded. As cyclin B degradation occurs at the metaphase-anaphase
      transition, subsequent to the microtubule integrity checkpoint, the delay induced
      by mutations at the thr locus defines a later point in mitotic progression.
      Chromosomes in the cells of thr embryos do not undertake anaphase separation, but
      remain at the metaphase plate. Subsequently they decondense. A subset of nuclei
      go on to replicate their DNA but there is no further mitotic division.

PMID- 8270647
TI  - Chediak-Higashi syndrome is not due to a defect in microtubule-based lysosomal
      mobility.
AB  - Chediak-Higashi Syndrome is an autosomal recessive disorder that affects
      intracellular vesicle formation. The diagnostic feature of Chediak-Higashi
      Syndrome is the presence of 'giant' lysosomes clustered near the nucleus.
      Lysosome morphology in macrophages is maintained by microtubules and microtubule
      based motors, such as kinesin. Dramatic changes in lysosome morphology can be
      induced by lowering cytoplasmic pH or by adding phorbol esters. When macrophages
      from beige mice (a murine homolog of Chediak-Higashi Syndrome) were subjected to
      these protocols they were able to alter their lysosomal distribution and
      morphology to the same degree as macrophages from control mice. These results
      indicate that lysosomes in Chediak cells are capable of interacting with the
      microtubule-based motor system, suggesting that the defective gene product is not
      an altered microtubular element involved in lysosomal movement.

PMID- 8270648
TI  - A rational approach to 5-aminosalicylic acid therapy in ulcerative colitis.

PMID- 8270649
TI  - Analysis of organophosphorus pesticides in rice by supercritical fluid extraction
      and quantitation using an atomic emission detector.
AB  - A rapid and sensitive method for the detection and quantitation of
      organophosphorus pesticides in rice has been developed. It uses extraction with
      methanol-modified supercritical carbon dioxide followed by quantitation by a gas
      chromatograph equipped with an atomic emission detector operating in the
      phosphorus and sulfur modes. Evaporative displacement of the collection solvent
      during the supercritical fluid extraction stage allows quantitation of the
      analyte down to 10 ng/g without any intermediate concentration steps.

PMID- 8270650
TI  - Rapid detection of viruses of the tick-borne encephalitis virus complex by RT-PCR
      of viral RNA.
AB  - Studies were performed to identify a pair of primers, specific for the tick-borne
      encephalitis (TBE) virus complex of the Flaviviridae, with which to develop a
      rapid and specific identification system based on reverse transcription and the
      polymerase chain reaction (RT-PCR). The specificity of a putative primer pair was
      examined by RT-PCR of representative viruses from other antigenic complexes of
      the Flaviviridae and by computer sequence homology checks. All viruses of the TBE
      complex tested, with a single exception, were identified by RT-PCR using the
      identified primer pair. Accumulated data suggest that one of the putative primers
      identified in these studies may have flavivirus group specificity. The advantages
      of such a primer in the development of identification systems for all virus
      complexes of the Flaviviridae is discussed.

PMID- 8270651
TI  - Detection of tick-borne encephalitis virus RNA in ticks (Ixodes ricinus) by the
      polymerase chain reaction.
AB  - A polymerase chain reaction for the detection of tick-borne encephalitis virus
      (TBEV) RNA in ticks was developed. Two pairs of primers for nested PCR were
      selected from the 5'-NCR and the 5'-terminus of the C protein coding region,
      which are highly conserved among the TBEV isolates sequenced so far. The
      sensitivity of the nested PCR was tested by dilution experiments of a TBEV
      positive brain suspension. The specificity of the PCR products was confirmed by
      Southern blotting. In a pilot study, 60 homogenates of 7200 ticks (I. ricinus)
      were examined by PCR. Two homogenates were found positive. The PCR for TBEV RNA
      appears to be a valuable method to define endemic areas of TBE.

PMID- 8270652
TI  - Production of herpes simplex virus fluorescein labelled typing reagents.
AB  - 29 herpes simplex virus monoclonal antibodies (MAbs) were produced and shown by
      indirect immunofluorescence assay (IIFA) to be HSV type specific or HSV cross
      reactive. Two HSV-1 and two HSV-2 specific MAbs were selected as HSV typing
      reagents on the basis of their specificity and the fluorescence pattern produced.
      When directly conjugated to fluorescein both reagents detected and correctly
      identified HSV isolates previously typed by restriction endonuclease analysis
      (REA). No cross reactions were observed with a panel of human viral pathogens.
      Assessment of these reagents in parallel with the Syva Microtrak Culture
      Identification/Typing Test indicated 100% concordance for the detection and
      typing of 80 clinical isolates.

PMID- 8270653
TI  - Antibody capture haemadherence tests for parvovirus B19-specific IgM and IgG.
AB  - In the absence of serum inhibitor human parvovirus B19 agglutinates primate red
      cells. Agglutination of baboon erythrocytes by inhibitor free baculovirus
      expressed VP1/VP2 proteins of B19 virus was enhanced by low pH. To avoid
      interference from inhibitor(s) present in serum specimens microtitre tests with
      an antibody capture configuration were designed and optimised. Antigen binding
      was demonstrated by the adherence of baboon erythrocytes. These tests (MACHAT,
      GACHAT) detected IgM or IgG anti-B19 in 1032 serum specimens with an overall
      sensitivity of 99%, specificity of 98.2% and positive predictive value of 96.8%
      with reference to the radioimmunoassays currently in diagnostic use. MACHAT and
      GACHAT are straightforward, and well suited to large scale research and
      seroepidemiological investigations. They are without the risks from infectious
      antigen and radiation associated with existing radioimmunoassays and allow the
      phenomenon of B19 virus haemagglutination to be put to practical advantage.

PMID- 8270654
TI  - Nested and multiplex polymerase chain reactions for the identification of
      bluetongue virus infection in the biting midge, Culicoides variipennis.
AB  - Two polymerase chain reaction tests for the detection of bluetongue viral (BLU)
      RNA in the principal North American insect vector, Culicoides variipennis, were
      developed. The BLU serogroup specific test used the highly expressed non
      structural protein 1 gene as the target gene and two amplification steps. First a
      1228 base pair product was amplified using an outer primer pair, then a second
      amplification using a nested or internal primer pair produced a 930 base pair
      product. This nested PCR test was found to be very sensitive detecting an
      equivalent to 1 plaque-forming unit of BLU viral RNA extracted from infected
      biting midges. The serotype specific test used a multiplex PCR approach in which
      five different primer pairs were used simultaneously. Each pair was based on the
      variable outer capsid protein VP2 gene of the five US serotypes generating
      specific product which were easily identified by size difference. The sensitivity
      of the multiplex PCR was less sensitive than the nested-PCR but sufficient for
      use with field collected samples. These tests provide valuable tools for
      epidemiologic studies of BLU disease.

PMID- 8270655
TI  - Use of bacterially-expressed antigen for detection of antibodies to the EBV
      specific deoxyribonuclease in sera from patients with nasopharyngeal carcinoma.
AB  - A cDNA clone, BG9, corresponding to the open reading frame BGLF5 of Epstein-Barr
      virus (EBV) DNase was inserted into an E. coli expression vector, pET3a, to
      generate a recombinant plasmid, pDNase 5. High level of expression of a DNase
      activity was detected in the E. coli transformed with pDNase 5 following
      induction with IPTG. The enzyme activity was purified using DEAE-cellulose,
      phosphocellulose and DNA-cellulose column chromatography. The purified protein
      appeared to be nearly homogeneous in SDS-PAGE using Coomassie blue staining. The
      requirement for divalent cations and optimum pH as well as inhibitory
      concentrations of ionic strength and polyamines for the purified enzyme activity
      were determined and seemed to be very similar to those of the enzyme activity
      purified from an EBV producing lymphoblastoid cell line. Using the purified
      enzyme as an antigen and anti-IgA as the secondary antibody, 82% (64/78) and 91%
      (71/78) of sera from patients with nasopharyngeal carcinoma (NPC) were shown to
      be positive by dot immunobinding assay and ELISA, respectively. The results
      suggest that purified E. coli expressed EBV DNase may be useful for preparing
      specific test for large scale screening of patients with NPC.

PMID- 8270656
TI  - Comparison of an ELISA system for the quantification of hepatitis B antibody with
      an automated and a semi-automated system.
AB  - In order to manage the increased workload resulting from post vaccination
      hepatitis antibody testing of health care workers, the anti-hepatitis B ELISA
      assay ETI-AB-AUK (Sorin Biomedica), adapted for quantification using standards
      available as an addition to the qualitative kit assay (ABAU-STD-SET, (Sorin
      Biomedica)) and a sample pre-dilution step, was compared with a fully automated
      microparticle enzyme immunoassay IMX AUSAB (Abbott Laboratories), and a semi
      automated enhanced luminescence system (Amerlite Amersham, now Kodak). Seventy
      eight samples were concurrently tested and analysed statistically using a
      Regression Coefficient computer package (Apple Mackintosh Cricket). Good
      quantitative agreement was observed with ELISA vs IMX giving a linear correlation
      coefficient (r = 0.96). The linear correlation coefficient for ELISA vs Amerlite
      was r = 0.77. This study validates the use of the automated IMX system and allows
      the comparison of IMX results with previous 'semi-quantitative' ELISA results
      when longitudinally assessing patients response to a recombinant hepatitis B
      vaccine.

PMID- 8270657
TI  - Estimates by computer simulation of genetic distances from comparisons of RNAse A
      mismatch cleavage patterns.
AB  - The RNAse A mismatch cleavage method was used to analyze genomic variability in
      RNA and DNA systems. However, there is no method which relates the digestion
      patterns observed to the extent of genetic variation. Here we report computer
      simulations which provide a simple estimator of genetic distances from the
      comparison of RNAse A digestion patterns. The results show that the number of non
      shared fragments is proportional to the number of mutations between each pair of
      sequences compared. This prediction is supported by the comparison of the RNAse A
      mismatch patterns and the nucleotide sequences of a set of influenza A (H3N2)
      hemagglutinin genes. The procedure allows a quantitative and reliable use of the
      RNAse A mismatch cleavage method.

PMID- 8270658
TI  - A comparison of the performance of nine commercially available anti-HTLV-I
      screening assays.
AB  - The performance of eight anti-HTLV-I enzyme immunoassays (EIAs) and one particle
      agglutination assay was compared with respect to sensitivity, specificity and
      delta values, by testing a panel containing 99 anti-HTLV-I positive and 126 anti
      HTLV-I negative samples which had been characterised by western blot and some by
      radioimmunoprecipitation assay. The estimated sensitivities produced by these
      assays ranged between 99% and 100% and estimated specificities were between 95.2%
      and 100%. The performance of the EIAs was further differentiated by using the
      delta value which measures the ability of an assay to separate the positive and
      negative populations from the cutoff value. A delta value could not be calculated
      for the particle agglutination assay (Serodia) because the test readings were not
      quantitative. The EIAs most likely to correctly identify anti-HTLV-I positive and
      anti-HTLV-I negative samples included the Cambridge Biotech, Dupont, Genetic
      Systems and Olympus assays. Our findings suggest that there may be some
      difficulty in correctly identifying anti-HTLV-I negative samples using the
      Abbott, Cellular Products Incorporated (CPI), Coulter and Diagnostic
      Biotechnology assays. The Serodia assay produced comparable sensitivity and
      specificity to the eight EIAs.

PMID- 8270659
TI  - Thumbsucking and tongue-posturing correction appliance.

PMID- 8270660
TI  - Glass ionomer update.

PMID- 8270661
TI  - Customized template for prefabricating initial lingual archwires.

PMID- 8270662
TI  - Effect of telephone reminders on appointment failure rate.

PMID- 8270663
TI  - Creating a team of practice builders.

PMID- 8270664
TI  - Disposable plaque-removal system.

PMID- 8270665
TI  - Breast masses with mixed cystic-solid sonographic appearance.
AB  - Retrospective analysis was performed for 56 breast masses with mixed cystic and
      solid sonographic patterns encountered in the last 5 years at Keio University
      Hospital, with the objective of elucidating their significance. The lesions were
      classified into two major groups: tumor with cyst (TWC--solid mass with cystic
      component) and intracystic tumor (ICT--cystic mass with solid component).
      According to the pathological diagnosis, 57% were benign and 43% were malignant.
      Fifty eight percent of malignant lesions were shown to have a TWC pattern and 42%
      an ICT pattern. Among benign lesions, 66% were shown to be TWC and 34% ICT. In
      malignant tumors, 96% of the cases showed irregular shape and heterogeneous
      internal content. Even in benign lesions, a high incidence of irregular shape and
      rough border was found, although the predominant internal echo texture was
      homogeneous, and three-dimensional (3-D) contour was not clear. In conclusion, we
      observed that in the TWC group, the lack of a defined 3-D contour is the most
      important criterion, and tumors with multiples cysts tend to be benign.

PMID- 8270666
TI  - Ultrasound-guided percutaneous galactography.
AB  - We present a new percutaneous ultrasound-guided galactography technique that may
      be used in patients in whom the conventional technique fails and breast
      ultrasonography show dilated ducts.

PMID- 8270667
TI  - A modified transvaginal sonographic technique for better ovarian evaluation.
AB  - Sonographic evaluation of the pelvis of postmenopausal women is not complete
      until both ovaries are scanned. Transvaginal sonographic examination combined
      with transabdominal screening is diagnostic in 85% of cases. Transvaginal
      examination performed with a partially full bladder significantly increased
      ovarian detection to 93.5% (p < 0.05).

PMID- 8270668
TI  - Effect of variations of heart rate within the normal range on renal artery
      Doppler indices in nonpregnant and pregnant women.
AB  - The effect of heart rate on Doppler indices in the renal artery was studied in 21
      nonpregnant, 17 normal and 27 preeclamptic pregnant patients. The central
      hemodynamics was evaluated by Doppler ultrasound in all pregnant women. The study
      demonstrated no influence of heart rate on renal artery Doppler indices. Central
      hemodynamic parameters, such as cardiac output, stroke volume, mean arterial
      pressure and total systemic resistance did not change with increasing heart rate.
      We do not recommend any correction of the renal artery Doppler indices for heart
      rate in the range considered clinically normal (60 to 95 beats/min). Above or
      below this range further investigations are required to determine if corrections
      would be necessary.

PMID- 8270669
TI  - The management of ovarian cysts by sono-guided transvaginal cyst aspiration.
AB  - Nineteen transvaginal, sono-guided ovarian cyst punctures were performed in 18
      patients. These patients, who were high surgical risks, were diagnosed to possess
      benign ovarian tumors as revealed with sonography. Aspiration curettage of the
      inner surface of the cyst present during aspiration was also performed to
      facilitate cytologic diagnosis. The recurrence rate was 11.1%. Sono-guided
      transvaginal cyst aspiration has been demonstrated here to be the treatment of
      choice for dealing with an ovarian cyst in patients at high surgical risk.

PMID- 8270670
TI  - Ultrasonic fetal weight estimation: analysis of inter- and intra-observer
      variability.
AB  - Standard ultrasound measurements were performed by two observers in 40 third
      trimester fetuses. Observers were blinded to the results of the measurements.
      Estimated fetal weight (EFW) was calculated using two published formulae. The
      intra-observer standard deviation for EFW, assessed using one-way analysis of
      variance, was < 75 g for both observers. The 95% prediction intervals for inter
      observer comparisons of EFW, calculated using the limits of agreement method,
      were -187.3 g to 139.8 g, and -159.9 g to 124.3 g, using the two formulae. The
      results suggest that measurements of EFW are reproducible. The prediction
      interval is comparable to the weekly fetal weight increment in normal fetuses.

PMID- 8270671
TI  - Investigation of abnormal first-trimester gestations by color Doppler imaging.
AB  - Color Doppler imaging was employed to assess the uteroplacental circulation in
      abnormal first-trimester gestations. Included in the study were 40 blighted ova,
      35 missed abortions, 10 trophoblastic diseases, and 3 ectopic gestations. Normal
      gestations served as a control group. Flow was detected more frequently in the
      blighted ova than in the missed abortions. Flow was detected in all cases of
      trophoblastic disease and ectopic gestations. Resistance to flow was
      significantly lower in the trophoblastic group as compared to the other groups.

PMID- 8270672
TI  - Budd-Chiari syndrome due to hepatic venous web: rapid color Doppler diagnosis.

PMID- 8270673
TI  - Abscess formation in hepatocellular carcinoma: complications of percutaneous
      ultrasound-guided ethanol injection.

PMID- 8270674
TI  - Ultrasonographic diagnosis of massive bladder hernia.

PMID- 8270675
TI  - Serial follow-up of abnormal flow velocity waveforms of dying fetus in a case of
      chronic hypertension.

PMID- 8270676
TI  - Ultrasonographic features of metastatic melanoma of the gallbladder.

PMID- 8270677
TI  - A proximal duodenal phytobezoar with gastric outlet obstruction: sonographic
      appearance.

PMID- 8270678
TI  - Transabdominal seeding of hepatocellular carcinoma after fine-needle aspiration
      biopsy.

PMID- 8270679
TI  - Sonographic findings of liver and gallbladder in early hemolysis, elevated liver
      enzymes, and low platelet count syndrome.

PMID- 8270680
TI  - Inhibition of plasmin by beta-lactoglobulin using casein and a synthetic
      substrate.
AB  - Bovine plasmin (EC 3.4.21.7) activity was measured on H-D-valyl-L-leucyl-L-lysyl
      4-nitroanilide and acid casein in the presence of native and heat-denatured beta
      lactoglobulin (denatured at 100 degrees C for 15 min before being mixed with
      plasmin solutions). Native or denatured beta-lactoglobulin was then heated with
      plasmin at 60 degrees C for 15 min. Enzyme activity again was estimated after
      this mild heat treatment. Native and denatured beta-lactoglobulin inhibited the
      action of plasmin on H-D-valyl-L-leucyl-L-lysyl-4-nitroanilide and casein. The
      mild heat treatment (60 degrees C for 15 min) caused stronger inhibition of the
      activity of plasmin against casein and the synthetic substrate. For H-D-valyl-L
      leucyl-L-lysyl-4-nitroanilide, inhibition was competitive in unheated mixtures,
      but heating beta-lactoglobulin with plasmin changed inhibition type to mixed.
      This change suggests a heat-dependent interaction between plasmin and beta
      lactoglobulin. Native beta-lactoglobulin was more inhibitory of plasmin's action
      against casein than was denatured beta-lactoglobulin. The converse was observed
      when plasmin activity was measured with the synthetic substrate.

PMID- 8270681
TI  - Microinjection of bovine embryos with a foreign gene and its detection at the
      blastocyst stage.
AB  - This study was designed to measure the survival and development of pronuclear
      stage bovine zygotes after microinjection with DNA and either culture in vitro or
      incubation in the sheep oviduct and to determine the percentage of embryos that
      retain exogenous DNA at the blastocyst stage. In vitro matured and fertilized
      oocytes were examined for pronuclear development 18 to 20 h after coincubation
      with sperm. An ovine somatotropin gene construct was microinjected into ova with
      visible pronuclei. Microinjected ova and unmanipulated ova from the same in vitro
      derived pool were cocultured with oviductal epithelial cells or incubated in the
      sheep oviduct and cocultured, respectively, for 7 d. Blastocysts were subjected
      to polymerase chain reaction analysis for detection of exogenous DNA. The
      percentage of cleaved embryos that formed blastocysts was similar for
      microinjected and unmanipulated cultured ova. The percentage of blastocysts
      recovered from the sheep oviduct that hatched was higher than for blastocysts
      that developed in coculture. Fourteen of 26 (54%) blastocysts that developed from
      microinjected ova were positive for the exogenous DNA by polymerase chain
      reaction. The implications are discussed for polymerase chain reaction detection
      of the exogenous gene construct in a relatively high proportion of microinjected
      blastocysts.

PMID- 8270682
TI  - Protein kinase C substrates and ganglioside inhibitors in bovine mammary nuclei.
AB  - In cow mammary gland, unlike in other tissues, gangliosides (putative physiologic
      regulators of protein kinase C) may be distributed in nuclei and on the cell
      surface. This study was designed to determine whether gangliosides and the
      protein kinase C system (the enzyme and its substrate proteins) are present in
      cow mammary gland nuclei and to examine the effect of gangliosides detected in
      nuclei on protein phosphorylation catalyzed by protein kinase C. Gangliosides
      GM3, GD3, and GT1b were detected in the highly purified nuclear fraction. The
      nuclear ganglioside pattern was different from those of whole tissue and cytosol,
      thereby suggesting the presence of the gangliosides in nuclei. Protein kinase C
      and its substrate proteins (120, 97, 56, 43, 38, and 36 kDa) were extracted by
      Triton X-100 treatment of nuclei. Both protein kinase C activity (histone
      phosphorylation) and the nuclear substrate phosphorylation were effectively
      inhibited by the three gangliosides. Of the gangliosides, GT1b was the most
      potent in inhibiting phosphorylation, followed by GD3 and GM3. These results
      suggest that signal transduction mediated by protein kinase C in cow mammary
      gland nuclei may be regulated by gangliosides.

PMID- 8270683
TI  - Relationships of body condition score to production variables in high producing
      Holstein dairy cattle.
AB  - Practical relationships were determined between milk production, health, and
      reproduction with the amount and use of body fat in high producing lactating
      Holstein dairy cattle. Approximately 350 cows and heifers > 15 mo of age in a
      high producing herd were assigned body condition scores at monthly intervals for
      24 mo. Production of 305-d FCM averaged 9541 kg (range 8826 to 10,818 kg). Body
      condition score at each of four calvings at 30, 60, 90, 120, and 305 DIM in each
      parity and loss in score in each lactation were summarized. Multiple regression
      related scores to milk and milk fat production, reproduction, and disease
      variables within and among lactations. No difference in score occurred at calving
      or at dry-off among parities. The range of body condition scores was less than is
      commonly reported; however, loss of condition increased with increasing parity
      from .3 in first lactation to .9 body condition score units in lactations > or =
      4. The body condition score varied quadratically with DIM but, at a given DIM,
      was not related to the daily milk production on that DIM. Parity had a stronger
      relationship with milk and milk fat production than did body condition score.
      However, within lactation, body condition score at calving and the loss of score
      were related quadratically to milk production. No significant relationships of
      body condition score to the incidences of pyometra, metritis, retained placenta,
      cystic ovarian disease, AI per conception, days to first AI, or dystocia existed
      in this herd.

PMID- 8270684
TI  - Effect of plane of nutrition of dairy heifers before and during gestation on milk
      production, reproduction, and health.
AB  - Fifty-nine heifers (1 yr of age; 320 +/- 12 kg) were assigned to one of four
      treatments of a 2 x 2 factorial design. Main effects were plane of nutrition (ad
      libitum vs. moderate feeding) during the second isometric phase (1 yr of age to 3
      mo of gestation) and during the second allometric phase (3 mo of gestation to 14
      d before calving) of mammary development. During the isometric phase, average
      daily gain were .72 and .84 kg/d for heifers fed a moderate or ad libitum diet,
      respectively. During the allometric phase, average daily gain was affected by
      previous plane of nutrition and averaged .84, .66, .95, and .73 for continuous ad
      libitum, ad libitum followed by moderate, moderate followed by ad libitum, and
      continuous moderate feeding, respectively. The BW at the end of gestation and BW
      after calving were increased by ad libitum feeding during the allometric phase
      (643 vs. 605; 588 vs. 558 kg, respectively). Milk production, protein content,
      and withers height were not affected by plane of nutrition. Milk fat was
      increased by ad libitum feeding during the isometric phase (3.9 vs. 3.6%). Cows
      on ad libitum feeding during the allometric phase had reduced average daily gain
      during lactation (.02 vs. .15 kg/d). The resumption of ovarian activity
      (progesterone > 1 ng/ml) was not affected by treatment, but days to first
      observed estrus increased with ad libitum feeding during the allometric phase.
      Finally, ad libitum feeding during isometric phase resulted in a higher incidence
      of displaced abomasum after calving, 9 versus 2.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270685
TI  - Severity of experimental Escherichia coli mastitis in ketonemic and nonketonemic
      dairy cows.
AB  - The severity of experimental Escherichia coli mastitis in relation to in vitro
      chemotaxis of polymorphonuclear leukocytes was investigated in cows during
      negative energy balance. The negative energy balance was induced by feed
      restriction. Cows were classified into two groups, ketonemic and nonketonemic,
      based on the beta-hydroxybutyrate concentration in the peripheral blood at the
      moment of inoculation. Bacterial growth in the inoculated quarter was used as a
      parameter to indicate the severity of experimental mastitis. In the nonketonemic
      cows, experimental mastitis ranged from moderate to severe. Severity of
      experimental mastitis was negatively related to preinfection chemotactic response
      of polymorphonuclear leukocytes. In contrast, the course of experimental mastitis
      in the ketonemic group was relatively severe in all cows, regardless of
      preinfection chemotactic response.

PMID- 8270686
TI  - Efficacy of intramammary antibiotic therapy for treatment of clinical mastitis
      caused by environmental pathogens.
AB  - For three California dairy herds with bulk tank SCC < 200,000/ml, twice daily
      milking, and no mastitis vaccine, 254 quarters with mild clinical mastitis were
      randomly assigned to three groups. Group A (n = 74) was treated with 62.5 mg of
      intramammary amoxicillin every 12 h for three milkings. Group C (n = 75) was
      treated with 200 mg of intramammary cephapirin every 12 h for two milkings. Group
      O (n = 105) was treated with 100 units of intramuscular oxytocin every 12 h for
      two or three milkings. Aseptic pretreatment quarter samples revealed 94 (37%)
      coliforms, 65 (26%) environmental streptococci, 34 (13%) other bacteria, and 61
      (24%) with no isolate on bovine blood agar plates. Contagious pathogens were not
      isolated. Clinical cure (return of quarter and milk to normal) and bacterial cure
      (absence of primary pathogen isolated pretreatment) were assessed at milking 8
      and d 20 after initial treatment. No difference existed in clinical (67.6, 67.7,
      or 66.7%) or bacterial (43.9, 55.0 or 49.1%) cure rate among groups. Clinical
      cure rates did not differ when quarters were grouped by etiology, but clinical
      cure rates for quarters with pathogens other than streptococci or coliforms were
      lower in group O.

PMID- 8270687
TI  - Interrelationships of somatic cell count, mastitis, and milk yield in a low
      somatic cell count herd.
AB  - In a high yielding low SCC herd, changes in milk yield associated with SCC and
      occurrence of clinical mastitis and differences in SCC with parity, clinical
      mastitis, and DIM were investigated. Milk yield data were obtained at every
      milking, and SCC was measured once every 48 h in 117 cows during the first 119 d
      postpartum. Effects of SCC and clinical mastitis on cumulative milk yield in the
      first 119 d postpartum were evaluated with least squares linear regression.
      Repeated measures ANOVA was used to detect changes in SCC. The SCC was highest at
      lactation onset, and cows with clinical mastitis had significantly higher SCC.
      During the 10 d prior to onset of clinical mastitis, SCC was higher in affected
      cows than in matched unaffected controls and surged just prior to diagnosis.
      During the 10-d period following a mastitis treatment, SCC differences between
      treated and control cows remained significant but became smaller with time and
      returned to the premastitis differences. Occurrence of clinical mastitis was
      associated with 5% milk yield loss. Cows with mean SCC > 245,000 cells/ml over
      the 119 d showed 6.2% yield loss compared with cows with SCC < or = 90,000
      cells/ml. Cows with clinical mastitis had higher SCC prior to and following the
      end of treatment for mastitis than did controls. Clinical mastitis and SCC were
      associated with significant yield loss. Milk yield loss attributed to clinical
      mastitis was greater than that associated with elevated SCC (> 245,000 cells/ml)
      because a greater percentage of cows (26%) had clinical mastitis than elevated
      SCC (12.5%).

PMID- 8270688
TI  - Distribution of clinical mastitis among quarters of the bovine udder.
AB  - Clinical mastitis episodes occurring from 1962 through 1991 in the Louisiana
      State University Dairy Research Herd were studied to determine the distribution
      of clinical mastitis among quarters of the udder. Data were detailed records of
      all mastitis episodes that occurred during 1630 Holstein lactations. Incidence of
      episodes, categorized according to which quarters within a cow were clinical for
      a given case, were compared with mathematical expectations based upon the
      assumption that quarters were independent. Results indicated that quarters within
      a cow were more alike with respect to clinical mastitis than would be expected if
      quarters were independent. More episodes occurred in which either no quarters or
      all four quarters were clinical. Deviation of observed frequencies from
      expectation could have resulted from generalized cow differences, such as cow
      milk yield, immune competency, mammary type characteristics, and general health.
      Front quarters had less clinical mastitis than rear quarters when all episodes
      were considered. No difference was observed in incidence between front and rear
      quarters when only first episodes in first lactations were considered. No
      difference was observed between incidence in left and right quarters. Diagonal
      pairs occurred less often than expected and at about half the frequency of other
      pairs. Dependence between quarters should be taken into consideration when
      experiments are designed and analyzed.

PMID- 8270689
TI  - Risk factors for downer cow syndrome.
AB  - A nested case-control study to detect risk factors for the development of the
      downer cow syndrome 30 d postpartum was conducted. Records from 2705 lactations
      from 12 Holstein dairy herds in the vicinity of Cornell University were collected
      prospectively between March 1981 and April 1985. Logistic regression was used to
      model the risk factors for downer cow syndrome. No confounding or modification
      effect by season of calving and parity was detected. The cumulative postpartum
      incidence rate for downer cow syndrome was 1.1%. Clinical hypocalcemia and
      stillbirth increased the risk of downer cow syndrome fivefold. An interaction
      term existed between dystocia and retained placenta.

PMID- 8270690
TI  - System of equations for fulfilling net energy and absorbed protein requirements
      for milk component production.
AB  - Objectives were to develop a system of equations for formulating rations to meet
      absorbed protein requirements, to define NEL requirements for individual milk
      components, and to evaluate the effects of changes in milk composition on
      requirements for absorbed protein and NEL recommended by NRC or by a proposed
      system based on milk components. By combining parameters in the NRC degradable
      protein system, a set of two equations was derived that can be solved to meet
      absorbed protein requirements when either ruminally available protein or energy
      limits microbial protein synthesis. Heats of combustion were used to estimate NEL
      requirements for milk components. Maintenance requirements for absorbed protein
      and NEL were obtained from NRC. To eliminate the dependence of DMI prediction on
      milk fat concentration, as assumed by NRC, DMI was estimated using the NDF
      concentration of the feed and the NEL requirement of the cow. The proposed system
      of requirements, based on milk components and the matrix of equations for meeting
      absorbed protein requirements, not only accounts for differences in the
      degradability and microbial yield of feeds but also more logically matches
      differences in nutrient requirements for milk components associated with changes
      in milk composition.

PMID- 8270691
TI  - Supplemental protein influences on carbohydrate degradation and bacterial 16S
      ribosomal ribonucleic acid.
AB  - This research examined the mechanism by which soybean protein stimulates growth
      of mixed ruminal anaerobes and degrades structural polysaccharides in vitro.
      Soybean meal, isolated soy protein, or branched-chain VFA was added to
      orchardgrass hay substrate in Experiment 1. Cell-wall degradation increased 14.5%
      over that of the control by protein addition. Protein addition resulted in 1.3-
      to 1.5-fold increases in bacterial growth. Hybridization with a 16S probe
      specific for Fibrobacter succinogenes indicated that protein addition did not
      influence the proportion of this species. For in vitro Experiment 2, optimal
      protein for cell-wall degradation was 2 g/L in cultures containing tall fescue
      hay. To determine whether protein stimulated microbial colonization of plant cell
      wall (Experiment 3), orchardgrass hay was placed in 14-L fermentors; treatments
      were control, NH3 N (2 g of N/L), or isolated soy protein (2 g of N/L). Addition
      of protein and NH3 N increased the extent of cell-wall disappearance 9.7% above
      control. Protein and ammonia improved cell-wall digestion, but protein had the
      greatest stimulatory effect on prokaryote growth with no preferential effect of
      F. succinogenes.

PMID- 8270692
TI  - Influence of amount and degradability of protein on production of milk and milk
      components by lactating Holstein cows.
AB  - Forty-one multiparous cows were utilized in a completely randomized design with a
      2 x 2 factorial arrangement of treatments to evaluate the amount and
      degradability of dietary CP on production of milk and milk components. The TMR
      contained 25% alfalfa haylage, 25% corn silage, and 50% concentrate to provide
      either 16.4 or 19.4% CP with a calculated ruminal degradability of 55 or 70%.
      Intakes of DM, ADF, and NDF and BW were not different among treatments.
      Production of milk, 4% FCM, fat, CP, and SNF was not affected by amount or
      degradability of dietary CP. Milk CP percentage was not affected significantly by
      amount or degradability of CP. Milk fat percentage was increased by the diet that
      was high in ruminally undegradable protein (2.90 and 3.12; low and high ruminally
      undegradable protein, respectively). These data suggest that synthesis of milk
      and milk components was not limited by a shortage of AA or that the different
      dietary sources of supplemental CP did not alter AA availability.

PMID- 8270693
TI  - Influence of amount and degradability of dietary protein on nitrogen utilization
      by dairy cows.
AB  - Four Holstein cows fitted with ruminal and T-type duodenal cannulas were utilized
      in a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments.
      The TMR contained 25% alfalfa haylage, 25% corn silage, and 50% concentrate and
      provided either 16.4 or 19.6% CP, with ruminal degradability calculated to be 30
      or 45%. Intakes of DM, OM, ADF, NDF, and N were not altered by either amount or
      degradability of CP. Intake and ruminal and postruminal digestibility of starch
      were greater when cows were fed diets high in undegradable CP but was not altered
      by amount of CP. Apparent total tract digestibilities for DM, OM, starch, ADF,
      and NDF were similar among treatments. Apparent total tract digestibility of N
      was 4.7 percentage units greater for diets low in ruminally degradable CP.
      Apparent digestibility of OM, ADF, and NDF and true digestibility of OM in the
      rumen were not altered by amount of CP or undegradable CP. Increasing the CP
      content of the diet and the proportion of undegradable CP in the diet increased
      NAN flow to the duodenum. Except for Met, flows of all AA to the duodenum were
      increased when CP was increased. Flow of Met to the duodenum was not altered by
      undegradable CP content of the diet. Production of milk, 4% FCM, and milk CP was
      not altered by amount of CP or undegradable CP. Milk fat content and yield were
      increased when diets high in undegradable CP were fed. Results suggest that all
      diets supplied adequate amounts of AA for these cows or that Met was deficient
      for all cows.

PMID- 8270694
TI  - Lactational response of dairy cows to change of degradability of dietary protein
      and organic matter.
AB  - The effect of variable degradability of both OM and CP, incorporated at a
      constant ratio in diets of high yielding dairy cows (35 kg/d), was studied under
      commercial dairy herd conditions. Two diets containing 17% CP were formulated,
      including high (70%) and low (65%) protein degradability. The ratio of rumen
      degradable OM to degradable protein was adjusted to 5:1 in both diets. Cows were
      assigned to treatments based on equal milk yield prior to trial, parity, and DIM.
      The trial lasted 7 wk: a reference week (wk 0), in which both groups were fed the
      high degradability diet, was followed by 6 experimental wk, in which group 1 was
      fed the high degradability diet and group 2 the low degradability diet. Cows on
      the low degradability diet consumed 1.2 kg more DM and yielded 1.5 kg/d more
      milk, .055 kg/d more milk protein, and .196 kg/d more milk fat. Percentages of
      milk protein (3.06 and 3.03) were similar, but fat (3.67 and 3.28) was higher for
      cows fed the low degradability diet. The results suggest that, when diets were
      formulated to balance rumen degradability of both OM and CP, 65% rather than 70%
      degradability of CP was advantageous for yields of milk and milk components.

PMID- 8270695
TI  - Nutrient digestion, nitrogen, and amino acid flows in lactating cows fed soybean
      hulls in place of forage or concentrate.
AB  - Five Holstein cows in early lactation were used in a 5 x 5 Latin square design to
      study substitution of soybean hulls for portions of forage or concentrate in
      diets. The control diet consisted of (DM basis) 10% alfalfa hay, 40% corn silage,
      25% high moisture corn, 23% protein supplement, and 2.3% vitamins and minerals.
      Soybean hulls were used to replace approximately 25 and 50% of the forage or
      concentrate DM in the control ration. The DMI decreased linearly as soybean hulls
      replaced forage. The DM and OM flow to the duodenum and apparent and true
      digestion of OM in the stomach were similar among treatments. Ruminal pH was
      similar among treatments, but concentrations of NH3 N decreased linearly when
      soybean hulls replaced forage. Total VFA concentrations were similar when soybean
      hulls replaced forage but showed a positive quadratic response when soybean hulls
      replaced concentrate. Microbial N averaged 59% of NAN flow and showed a negative
      quadratic response when soybean hulls replaced concentrate. Flows of total AA and
      total essential AA to the duodenum were not altered when soybean hulls were fed.
      Yields of milk and milk components were similar among treatments; hulls can be
      used effectively to replace forage or concentrate in lactation diets.

PMID- 8270697
TI  - Feeding practices and income over feed cost on pasture-oriented dairy farms in
      Louisiana.
AB  - Monthly summary reports (n = 15,568) of Holstein herds enrolled in the Louisiana
      DHIA program from February 1984 through April 1990 were analyzed using multiple
      regression techniques to determine the relationships between feeding practices
      and income over feed cost on predominantly pasture-oriented dairy farms. Income
      over feed cost increased as silage and pasture quality score increased and
      decreased as hay and concentrate increased. Milk yield increased as silage and
      concentrate increased. Increased hay was associated with lower milk yield, but
      the overall difference was small. Comparison of feeding practices overall with
      the top 10% of herds based on income over feed cost indicated that most dairy
      farmers were not adjusting amount of concentrate to nutritional needs. Additional
      silage fed during late summer and fall, when permanent pastures were at lowest
      quality and winter pastures were not productive, improved income over feed cost
      and herd reproductive performance. Better utilization of concentrate by
      adjustment of amounts fed for milk yield, stage of lactation, and forage
      component of ration would increase milk yield and income over feed cost.
      Increased utilization of silage is suggested for better financial and productive
      performance of the pasture-oriented dairy farms studied.

PMID- 8270696
TI  - Effect of whole crop cereal grain silage substituted for alfalfa silage on
      performance of lactating dairy cows.
AB  - Barley, oats, and triticale were planted at the University of Alberta Research
      Station May 22 to June 1, 1990, harvested August 5 to August 19, 1990, at the
      early to mid-dough stage, and ensiled. Second-cutting alfalfa was harvested at
      midbloom and ensiled. Twenty Holstein cows in early lactation and 24 in
      midlactation were subjected to a 21-d standardization period (covariate) and were
      fed a TMR (50:50, forage: concentrate). Forage was a combination of equal
      portions of silage of alfalfa, barley, oats, and triticale. Following the
      covariate period, cows were offered TMR for ad libitum intake for 12 wk in which
      the forage portion of the TMR was one of the four silages. Diets based on oat and
      triticale silages lowered DMI, but overall milk production was not significantly
      different across treatments. Digestibilities of DM, OM, CP, and ADF were highest
      for the alfalfa silage diet, intermediate for the barley silage diet, and lowest
      for diets based on oat and triticale silages. The high dietary NDF concentration
      in oat and triticale silage limited feed intake. However, forage source had no
      major effect on dairy cow performance when forage was fed for ad libitum intake;
      therefore, barley, oat, and triticale silages harvested at an early stage of
      maturity can be used effectively in dairy cow rations.

PMID- 8270698
TI  - Performance of dairy cows fed short staple, Pima, and cracked Pima cottonseed and
      feed characteristics.
AB  - Compared with short staple cottonseed, Pima cottonseed was higher in CP, ether
      extract, and oleic acid and lower in NDF, ADF, and linoleic acid. Pima cottonseed
      had greater bulk density, but short staple cottonseed had stronger seed coat
      strength; Pima cottonseed contained more of the (-)-gossypol isomer than short
      staple cottonseed. Lactating Holstein cows were fed whole short staple
      cottonseed, whole Pima cottonseed, and cracked Pima cottonseed at 15% of dietary
      DM for 70 d after a pretrial covariate period. The DMI was not significantly
      different among treatments, but cows fed whole Pima tended to yield less milk
      than those fed short staple and less FCM than those fed cracked Pima. Feed
      efficiency was improved by processing Pima cottonseed. Milk fat content was
      higher for whole and cracked Pima than for short staple cottonseed; gross feed
      efficiency was greatest for cows fed cracked Pima cottonseed. Whole cottonseed in
      feces was highest for whole Pima, intermediate for short staple, and negligible
      for cracked Pima cottonseed. Concentrations of milk stearic acid were lower, and
      linoleic acid higher, for cows fed cracked Pima than for cows fed short staple
      cottonseed. Total tract digestibility of ADF was least on the cracked Pima
      cottonseed diet, and ether extract digestibility was higher on cracked than on
      whole Pima cottonseed diets.

PMID- 8270699
TI  - Effect of three supplemental fat sources on lactation and digestion in dairy
      cows.
AB  - Tallow, Ca salts of palm fatty acids, or prilled fatty acids were added at 2.5%
      to a control diet (3.7% fatty acids) containing 7.2% ammoniated whole cottonseed.
      Diets were fed to midlactation cows (6 cows per treatment) for 72 d to determine
      effects of fat supplementation and fat source on lactation performance and
      nutrient digestibilities. Dry matter intake did not differ among treatments. Milk
      yield was 31.6 kg/d for the control and increased an average of 2.1 kg/d with fat
      supplementation. Source of supplemental fat did not significantly affect
      lactation performance. Added fat decreased milk protein content but did not
      affect protein yield. Milk fat, lactose, and SNF contents did not differ among
      treatments. Overall fat supplementation did not affect digestibilities of DM,
      ADF, or NDF but decreased digestibility of fatty acids. Contribution of de novo
      fatty acids to milk fat was decreased with fat supplementation. Addition of 2.5%
      fat to a diet containing a medium amount of fat from whole cottonseed increased
      milk yield. Tallow, Ca salt of palm fatty acids, and prilled fatty acids did not
      differ in milk yield response.

PMID- 8270700
TI  - Influence of dietary buffer value index on the ruminal milieu of lactating dairy
      cows fed sorghum silage and grain.
AB  - The objective of this study was to evaluate the influence of dietary buffer value
      index on ruminal fluid pH, buffering capacity, and buffer value index in
      lactating cows. Three Holstein cows averaging 18 +/- 10 DIM were used in a 3 x 3
      Latin square with 3-wk experimental periods. Diets contained grain:sorghum silage
      DM ratios of 50:50, 60:40, and 70:30. By analysis, these diets had buffer value
      indexes of -74, -41, and -7. The analyzed dietary buffer value index of the total
      diets was higher than the index that was calculated from the buffer value index
      of individual ingredients. Although milk fat content tended to be highest for
      milk from cows fed the 50:50 concentrate to forage diet and although milk protein
      production was highest for cows fed the 70:30 concentrate to forage diet, milk
      yield, 4% FCM, milk fat yield, protein content, and milk fat content were not
      significantly affected by dietary buffer value index. Dietary buffer equivalents
      were calculated to be 11% of total buffering equivalents available to the cow,
      and dietary acid equivalents were 15% of total acid production in the rumen.
      Compared with ruminal acid production and salivary buffering in the rumen,
      dietary acid and dietary buffer contributions to the acid-base balance of the cow
      are minor quantitatively. Ruminal fluid pH, hydrogen ion concentration, buffer
      value index, buffering capacity, and total VFA were not affected significantly by
      dietary buffer value index. Hence, dietary acid-base status alone is inadequate
      as a predictor of the need for buffers in the diet of lactating cows.

PMID- 8270701
TI  - Influence of level of deoxynivalenol in the diet of dairy cows on feed intake,
      milk production, and its composition.
AB  - Eighteen primiparous Holstein cows were used in a 10-wk lactation study, preceded
      by a 2-wk covariate period, to determine the effect of concentration of
      deoxynivalenol in the diet on cow performance and transfer of deoxynivalenol and
      its metabolite, deepoxydeoxynivalenol, to milk. Diets were formulated to contain
      deoxynivalenol at 0, 6, and 12 mg/kg of concentrate DM, and daily intake of
      deoxynivalenol was .59, 42, and 104 mg, respectively. Increasing deoxynivalenol
      in the diet did not affect intake of concentrate or forage. Total milk output was
      not affected; however, milk fat responded quadratically; cows given
      deoxynivalenol at 6 mg/kg of concentrate DM had the lowest milk fat content and
      fat output. Overall energetic efficiency was not influenced because reduced
      energy output in milk was compensated by increased BW gains. No transfer of
      deoxynivalenol or deepoxydeoxynivalenol to milk was observed; concentrations were
      below detectable limits (1 microgram/ml) using HPLC-mass spectroscopy. We
      concluded that diets containing deoxynivalenol up to 6 mg/kg of dietary DM did
      not reduce feed intake of cows in this study and that deoxynivalenol or
      deepoxydeoxynivalenol was not transferred to milk. Further studies are required
      to confirm the apparent lack of effect of deoxynivalenol on milk production.

PMID- 8270703
TI  - Genetic parameters of Italian brown Swiss for levels of herd yield.
AB  - Genetic parameters were estimated for yields and percentages of milk, fat, and
      protein for registered Italian Brown Swiss cows. Data were 72,690 mature
      equivalent 305-d first lactation yields split by herd average milk into four
      files. An expectation-maximization REML algorithm was used on a multiple-trait
      model with equal design matrices for fixed and random effects. Data were
      preadjusted for geographical area, age-month of calving, and days open. The model
      included herd-year and sire genetic group as fixed effects and sires as random
      effects. Estimates of heritability were .28, .30, .26, .42, and .34 for milk,
      fat, and protein yields, and fat and protein percentages, respectively. Genetic
      correlations of milk yield and milk component percentages were negative, as
      expected. Correlation of protein yield and protein percentage was null. Results
      show an increasing tend of variance components from low to high herd yields,
      indicating that dispersion of yield about the mean increases as average yield
      increases. Relative differences among environmental components were larger than
      those among genetic components, yielding larger estimates of heritability in
      herds with lower yield. Estimates of heritability for milk from low to high herd
      yields were .42, .38, .35, and .33.

PMID- 8270702
TI  - Deposition of copper, manganese, zinc, and selenium in bovine fetal tissue at
      different stages of gestation.
AB  - Developmental changes of Cu, Mn, Zn, and Se in fetal liver and kidney and the
      intracellular distributions were determined. Fetuses were obtained from crossbred
      beef heifers (n = 25) that were slaughtered at different stages of pregnancy.
      Fetal age was estimated from crown to rump measurements. Selenium concentration
      of fetal liver increased from d 145 to 195 but decreased from d 195 to 245. Fetal
      age did not affect Cu, Mn, or Zn in fetal liver and kidney or Se in kidney. Bone
      Ca significantly decreased with fetal age, but neither bone P nor Ca:P ratio
      changed. Liver Zn concentrations were correlated negatively with kidney Mn but
      positively with liver Se. Within fetal liver, the crude nuclear fraction had the
      largest amount of Cu, and the largest amounts of Zn and Mn were in the cytosolic
      fractions. The ribosomal fractions contained the least Cu, Zn, and Mn. Results
      indicate the normal changes that occur in tissue concentrations of minerals in
      the developing bovine fetus. Storage of minerals in fetal tissue reflects fetal
      demands for growth and the ability of the dam to transfer minerals.

PMID- 8270704
TI  - Absence of quadratic relationships between genetic evaluations for somatic cell
      scores and udder linear traits.
AB  - Sire genetic evaluations for lactation average somatic cell scores from first and
      second lactation daughters were regressed in separate models on genetic
      evaluations for udder linear traits. Somatic cell scores were from Pennsylvania
      DHIA, and udder linear scores were from the Holstein Association of America
      classifications of first lactation cows in the northeastern US excluding
      Pennsylvania. The independent data files for calculation of genetic evaluations
      included 108,632 cows from 301 sires with udder linear scores and 58,235 cows
      from the same 301 sires with somatic cell scores. Sire genetic evaluations for
      higher udders, stronger fore udder attachments, closer teat placement, and
      shorter teats were associated with lower somatic cell scores. Quadratic
      relationships between genetic evaluations for the udder traits and somatic cell
      scores were not important. Quadratic components were significant only for somatic
      cell scores and teat length. Evaluations for intermediate teat length tended to
      be associated with higher somatic cell score evaluations. Selection and mating
      for intermediate udder depth, fore udder attachment, and front teat placement
      scores are not as effective in reducing somatic cell scores as selection for
      higher udders, stronger fore udders, and closer front teats.

PMID- 8270706
TI  - The program directors' perspective on the goals and objectives of advanced
      general dentistry training.
AB  - In September of 1991, all postgraduate general dentistry (PGD) program directors
      (Advanced Education in General Dentistry [AEGD] and General Practice Residency
      [GPR] directors [n = 325]) were surveyed to ascertain their opinions of the ideal
      goals and objectives of PGD programs. The response rate was 81.5 percent (n =
      265). The directors rated the relative importance of various PGD program goals
      and objectives. The average of all the items rated was 3.4 on a scale ranging
      from 1 = unimportant to 4 = very important. The respondents identified several
      clinical and didactic subject areas that they considered very important
      including; infection control, CPR, dental and medical emergencies, diagnosing
      dentoalveolar trauma, diagnosing oral pathology, and assessment and treatment of
      patients with medical conditions. They also identified several training areas
      which were beyond the scope of a PGD program, e.g., research techniques,
      pediatric sedation, and selected advanced clinical procedures in dentistry
      (implantology and orthodontics) which require a long time to complete. In
      general, there was substantial agreement among the directors of different program
      types and sites as to the relative importance of various program goals. The
      largest differences were found among directors of programs from different sites,
      e.g., hospitals versus dental schools as opposed to directors from different
      program types, e.g., GPR versus AEGD. There is now a need to determine the
      relationship of these identified idealized goals and differences to program
      outcomes for the graduates of PGDs.

PMID- 8270705
TI  - A comparison of ozonation and chlorination for the disinfection of stainless
      steel surfaces.
AB  - Ozonated water and chlorinated sanitizer were compared for effectiveness against
      biofilms of milk spoilage bacteria. Stainless steel plates were incubated in UHT
      pasteurized milk inoculated with pure cultures of either Pseudomonas fluorescens
      (ATCC 949) or Alcaligenes faecalis (ATCC 337). After incubation, the plates were
      removed and rinsed in sterile PBS. A control rinsed stainless steel plate was
      swabbed and plated on standard plate count agar. A second rinsed stainless steel
      plate was covered and treated for 2 min with a commercial chlorinated sanitizer
      (dichloro-s-triazinetrione), prepared according to the manufacturer's
      recommendations; after treatment, the plate was rinsed twice in sterile PBS,
      swabbed, and plated on standard plate count agar. A third rinsed stainless steel
      plate from the culture was placed in ozonated deionized H2O (.5 ppm of ozone) for
      10 min, rinsed twice as described, swabbed, and plated. Both ozonation and
      chlorination reduced bacteria populations by > 99% at initial cell densities in
      the range of approximately 1.24 x 10(5) to 8.56 x 10(5) cfu/cm2 for P.
      fluorescens and 1.53 x 10(4) to 8.56 x 10(5) cfu/cm2 for A. faecalis in milk
      films on stainless steel surfaces.

PMID- 8270708
TI  - Written statement of the American Association of Dental Schools to the Institute
      of Medicine Committee on the Future of Dental Education.

PMID- 8270707
TI  - A dental school's experience with the death of an HIV positive faculty member.

PMID- 8270709
TI  - Oral testimony to the Committee on the Future of Dental Education, Institute of
      Medicine.

PMID- 8270711
TI  - Dental schools are members of the academy: survival demands a primary focus on
      scholarship.

PMID- 8270710
TI  - Dental schools are educational institutions: top priority must be given to
      teaching and learning.

PMID- 8270712
TI  - The recording of FRC--is it of importance and can it be made simple?

PMID- 8270713
TI  - Microbiological diagnosis of ventilator-associated pneumonia: to direct or not to
      direct samplings?

PMID- 8270714
TI  - Barotrauma and alveolar recruitment.

PMID- 8270715
TI  - A simple method to estimate functional residual capacity in mechanically
      ventilated patients.
AB  - OBJECTIVE: The aim of the present study was to evaluate a simplified method for
      FRC measurement. DESIGN: Accuracy and precision of the method were assessed in a
      physical lung model; reproducibility was tested in 10 mechanically ventilated
      patients. In each patient FRC was measured at three PEEP levels. SETTING: Post
      operative intensive care unit in a university hospital. MEASUREMENTS AND RESULTS:
      Gas flow, CO2 concentration, and O2 concentration were measured during in- and
      expiration by pneumotachography, a mainstream capnometer and a sidestream O2
      analyser. For FRC-measurement inspiratory O2 concentration was changed by 30%.
      FRC was determined as mean value of a N2 washout and N2 washin procedure.
      Evaluation of this method in a lung model shows a good correlation between FRC
      set in the lung model and FRC measured (FRC measured = 1.028*FRG model + 22.92
      ml; r2 = 0.957; n = 30). The mean difference was 4.4% of FRC-reference (range 
      8.4% to +21.7%). Duplicate determinations in 10 mechanically ventilated patients
      differed by an average of -2.7% (range -30.1% to +27.3%). CONCLUSION: Our results
      suggest that the proposed method can be used in daily clinical work.

PMID- 8270716
TI  - Diagnosis of nosocomial pneumonia in mechanically ventilated patients by the
      blind protected telescoping catheter.
AB  - OBJECTIVES: To demonstrate that blind insertion of the protected telescoping
      catheter (PTC-NB) through the orotracheal tube can provide reliable pulmonary
      samples for the diagnosis of nosocomial pneumonia (NP) in ventilated patients.
      DESIGN: We performed a random comparison between the protected telescoping
      catheter introduced through a bronchofiberscope (PTC-B) and the PTC-NB to
      diagnose NP. SETTING: A general intensive care unit of a University Hospital.
      PATIENTS: 40 consecutive patients on mechanical ventilation and with suspicion of
      NP. The diagnosis of NP was suspected by clinical and chest X-ray findings.
      MEASUREMENTS AND RESULTS: NP was confirmed microbiologically in 26 (65%) patients
      and maintained in 8 patients by clinical and radiological criteria. PTC-NB
      confirmed the microbiological diagnosis of PN in 21 (80%) patients. The use of
      antibiotics prior taking respiratory samples reduced the sensitivity of PTC-NB
      and PTC-B from 100-74% and from 94-70% (p = 0.001). Both techniques agreed in 24
      of 33 (73%) patients but such agreement was better when PN was on the right lung.
      Two patients developed a self-limiting hemoptysis after the PTC-B procedure.
      CONCLUSIONS: PTC-NB is as sensitive as specific as PTC-B for diagnosing PN in
      mechanically ventilated patients, being a much easier technique to use.

PMID- 8270717
TI  - Histologic aspects of pulmonary barotrauma in critically ill patients with acute
      respiratory failure.
AB  - OBJECTIVE: To describe histologically pulmonary barotrauma in mechanically
      ventilated patients with severe acute respiratory failure. DESIGN: Assessment of
      histologic pulmonary barotrauma. SETTING: A 14-bed surgical intensive care unit
      (SICU) PATIENTS: The lungs of 30 young critically ill patients (mean age 34 +/-
      10 years) were histologically examined in the immediate post-mortem period. None
      of them were suspected of pre-existing emphysema. MEASUREMENTS AND RESULTS:
      Clinical events and ventilatory settings used during mechanical ventilation were
      compared with lung histology. Airspace enlargement, defined as the presence of
      either alveolar overdistension in aerated lung areas or intraparenchymal
      pseudocysts in nonaerated lung areas, was found in 26 of the 30 lungs examined
      (86%). Patients with severe airspace enlargement (2.6-40 mm internal diameter)
      had a significantly greater incidence of pneumothorax (8 versus 2, p < 0.05),
      were ventilated using higher peak airway pressures (56 +/- 18 cmH2O versus 44 +/-
      10 cmH2O, p < 0.05) and tidal volumes (12 +/- 3 ml/kg versus 9 +/- 2 ml/kg, p <
      0.05), were exposed significantly longer to toxic levels of oxygen (8.6 +/- 9.4
      days versus 1.9 +/- 2 days at FIO2 > 0.6, p < 0.05) and lost more weight (6.3 +/-
      9.2 kg versus 0.75 +/- 5.8 kg, p < 0.05) than patients with mild airspace
      enlargement (1-2.5 mm internal diameter). CONCLUSION: Underlying histologic
      lesions responsible for clinical lung barotrauma consist of pleural cysts,
      bronchiolar dilatation, alveolar overdistension and intraprenchymal pseudocysts.
      Mechanical ventilation appears to be an aggravating factor, particularly when
      high peak airway pressures and large tidal volumes are delivered by the
      ventilator.

PMID- 8270718
TI  - Angiotensin-converting enzyme activity in serum and bronchoalveolar lavage fluid
      after damage to the alveolo-capillary barrier in the human lung.
AB  - OBJECTIVE: Angiotensin-converting enzyme (ACE) is considered as a possible marker
      for endothelial cell damage in serum or bronchoalveolar lavage fluid. This
      hypothesis was tested during cardiac surgery and during the adult respiratory
      distress syndrome. DESIGN: We used patients with an expected different degree of
      endothelial cell damage. ACE levels in serum and bronchoalveolar lavage fluid
      were compared with indirect markers of alveolo-capillary barrier integrity.
      SETTING: Interdisciplinary team in a university hospital. METHODS: 13 Cardiac
      surgery patients received no glucocorticoids and 13 others received 2 g
      methylprednisolone before extracorporeal circulation. Thirteen patients were used
      as controls and 15 patients had nonseptic adult respiratory distress syndrome.
      All underwent bronchoalveolar lavage for ACE determination. RESULTS: At different
      times during surgery serum angiotensin-converting enzyme levels were not
      significantly different between the two groups. In post-operative bronchoalveolar
      lavage fluid, angiotensin-converting enzyme levels were significantly higher in
      patients who received corticoids (27.8 +/- 1.7 U/l, mean +/- SEM), compared to
      patients without corticoids (19.8 +/- 1.4 U/l), control patients (18.2 +/- 1.3
      U/l) or patients with full blown non-septic adult respiratory distress syndrome
      (18.8 +/- 1.1 U/l). There were no correlations between lavage angiotensin
      converting enzyme and other parameters for alveolo-capillary membrane integrity
      in the lavage fluid such as the number of neutrophil cells, albumin or protein
      concentration, and between lavage angiotensin-converting enzyme and PaO2/FIO2
      ratio during lavage. CONCLUSION: Angiotensin-converting enzyme activity in serum
      or bronchoalveolar lavage fluid does not reflect damage of endothelial cells or
      damage of alveolocapillary integrity in acute pulmonary disease.

PMID- 8270720
TI  - Comparison of atracurium and pancuronium in mechanically ventilated neonates.
AB  - OBJECTIVE: To compare haemodynamic and gas exchange effects after either
      atracurium or pancuronium given to ventilated neonates with respiratory failure.
      DESIGN: In this prospective study neonates were alternately assigned to receive
      either atracurium or pancuronium, intravenously. SETTING: Paediatric and neonatal
      ICU in a teaching hospital. PATIENTS: 21 ventilated neonates with mean birth
      weight of 2293 g, suffering from respiratory distress syndrome, meconium
      aspiration syndrome or pneumonia were included in the study. Patients were
      entered if they were breathing out of phase with the ventilator and required FIO2
      > 0.4 and peak inspiratory pressure (PIP) > 15 cm H2O. Exclusion criteria were
      unstable haemodynamics or a pneumothorax. INTERVENTIONS: Heart rate, respiratory
      rate, invasive blood pressure and transcutaneous oxygen tension were monitored
      continuously. IV atracurium (0.3 mg/kg) or pancuronium (0.1 mg/kg) were
      administered. Arterial blood gas analysis was performed before and 10 min after
      injection of muscle relaxant. MEASUREMENTS AND RESULTS: Atracurium caused a
      significant decrease in heart rate (p < 0.05), systolic and mean blood pressure
      (p < 0.01). There was also a slight decrease in PaO2 and PaCO2 (n.s.).
      Administration of pancuronium resulted in an increase in heart rate (p < 0.01)
      and a slight decrease of blood pressure (n.s.). PaCO2 remained unchanged, whereas
      PaO2 increased slightly (n.s.). The PtcO2 index (PtcO2/PaO2) decreased after
      atracurium and did not change after pancuronium (both n.s.). With both drugs a
      slight increase in alveolar to arterial oxygen tension difference was observed
      (n.s.). There was one episode of hypotension and one of hypoxaemia--both after
      pancuronium. CONCLUSION: Both drugs may be used for muscle relaxation in neonates
      with respiratory failure. Atracurium however causes more cardiovascular
      depression, whereas the effect of pancuronium may be difficult to predict.

PMID- 8270719
TI  - Post-operative circulating cytokine patterns--the influence of infection.
AB  - OBJECTIVE: To study post-operative plasma concentrations of tumor necrosis factor
      alpha (TNF), interleukin-1 beta (IL-1) and interleukin-6 (IL-6) in infected and
      non-infected patients. DESIGN: Prospective controlled clinical study. SETTING:
      The intensive care unit (ICU) of a university hospital. PATIENTS AND
      PARTICIPANTS: The study comprised 20 patients, 9 infected and 11 non-infected,
      consecutively admitted to the ICU after moderate or major surgery. Twelve healthy
      volunteers were used as controls. MEASUREMENTS AND RESULTS: Leucocyte count, CRP
      and the plasma TNF, IL-1 and IL-6 concentrations were studied 24-48 h after the
      start of surgery. Axillary temperature, the duration of surgery, the number of
      packed red cells transfused, the APACHE II score and outcome were registered.
      Both infected and non-infected patients had higher plasma concentrations of IL-6
      than the controls (p < 0.001 and p < 0.01 respectively). Patients with infection
      had a higher plasma IL-6 concentration than non-infected patients (p < 0.05).
      Similar analyses of plasma TNF concentrations revealed no differences between
      infected and non-infected patients. Plasma IL-1 was detected only occasionally.
      Non-survivors (n = 4) had higher plasma concentrations of TNF and IL-6 than
      survivors (p < 0.05 and p = 0.05 respectively). In non-infected patients a
      correlation between the number of units of packed red cells transfused and the
      plasma IL-6 concentration was observed (r = 0.73, p < 0.05). CONCLUSION: No
      specific plasma cytokine pattern for infected patients subjected to surgery was
      observed. The effect of surgery and infection on the plasma IL-6 concentration
      seemed to be additive. Transfusion of packed red cells appeared to elevate the
      post-operative plasma IL-6 concentration.

PMID- 8270721
TI  - High-frequency ventilation and conventional mechanical ventilation in newborn
      babies with respiratory distress syndrome: a prospective, randomized trial.
AB  - OBJECTIVE: Morbidity and mortality remain high amongst babies ventilated for a
      respiratory distress syndrome (RDS). Whether newly developed ventilators allowing
      high frequency ventilation such as high frequency flow interrupted ventilation
      (HFFIV) could decrease the morbidity and the mortality was investigated in a
      randomized study. DESIGN: Preterm babies weighing < or = 1800 g suffering from
      RDS and ventilated by conventional mechanical ventilation (CMV) were randomized
      to be further ventilated either by CMV (group CMV) or by HFFIV (group HFFIV) when
      peak inspiratory pressure (PIP) on CMV was > or = 20 cmH2O. SETTING: The study
      was undertaken in the neonatal intensive care unit of the Erasmus Hospital.
      PATIENTS: 24 patients entered into the investigation and were randomized but 2
      patients were removed from the study because the switch over to HFFIV failed.
      Eight of the 12 CMV patients and 5 of the 10 HFFIV patients completed the study.
      MEASUREMENTS AND RESULTS: Clinical variables, blood gas analysis and ventilatory
      variables were looked at. There were no differences in mortality, in incidence of
      air leaks and pulmonary complications or in blood gas analysis. Bronchopulmonary
      dysplasia was not decreased by the use of HFFIV. CONCLUSION: It is concluded that
      HFFIV is safe although it offers no concrete advantages over CMV when applied as
      we did in a low pressure approach.

PMID- 8270722
TI  - Assessment of lung volume and alveolar pressure during combined high-frequency
      jet ventilation in a child with adult respiratory distress syndrome.
AB  - Lung volume and alveolar pressure were assessed using inductance plethysmography,
      airway occlusion and pneumotachography in a child with severe adult respiratory
      distress syndrome during both conventional mechanical and combined high-frequency
      ventilation (HFJV). The results suggest that improved oxygenation during combined
      HFJV is associated with higher end-expiratory lung volume and lower peak and mean
      lung volume and alveolar pressure.

PMID- 8270723
TI  - Management of intra-abdominal organ injury following blunt abdominal trauma in
      children.
AB  - OBJECTIVE: To evaluate the strategy of a combined diagnostic and therapeutic
      approach in children with intra-abdominal organ injury following blunt abdominal
      trauma. DESIGN: Retrospective clinical study. SETTING: Pediatric intensive care
      unit of an university hospital. PATIENTS: 38 children with documented intra
      abdominal injury. INTERVENTION: Initial non-surgical treatment by a team of
      pediatric intensivists, radiologists and surgeons. MEASUREMENTS AND RESULTS:
      Physical examination, oriented blood and urine tests, plain abdominal film,
      abdominal ultrasound (US) and computed tomography (CT) with contrast. US
      documented intra-abdominal fluid in 30 and initial organ lesion in 14 out of 31
      patients evaluated. Abdominal CT demonstrated the precise organ lesion in 34 out
      of 36 patients examined with solid organ lesion. Early laparotomy was needed in 7
      because of severe shock, pneumoperitoneum and ruptured diaphragm, and delayed
      surgery in 6 patients. All 38 patients regained a normal life. CONCLUSIONS: The
      stepped diagnostic approach combined with initial non-surgical treatment by a
      team provided accurate diagnosis and appropriate treatment. Abdominal US, by
      demonstrating free intra-abdominal fluid is very sensitive to detect patients
      with intra-abdominal organ injury, CT scan with contrast is needed to give
      precise information of specific organ lesions.

PMID- 8270724
TI  - Resuscitation after severe hypoxia in a young child: temporary isoelectric EEG
      and loss of BAEP components.
AB  - EEG and multimodality evoked potentials are currently used to ascertain brain
      death. We have observed electrocerebral silence (ECS) and loss of wave IV and V
      in BAEP in a 28-month-old child, 2 h after resuscitation from severe hypoxia,
      followed by reappearance of EEG activity and of waves IV and V (latencies and
      amplitudes within normal range) 18 h later. Temporary loss of EEG activity has
      been observed occasionally, while rapid reoccurrence of BAEP waves IV and V was
      unexpected and in contrast to the common observation, that rostro-caudal loss of
      BAEP waves is irreversible. This observation suggests that temporary loss of BAEP
      waves IV and V may occur and that caution is necessary in the interpretation of
      BAEP recorded immediately after a resuscitation.

PMID- 8270725
TI  - Chemical monitoring of intensive care patients using intravenous microdialysis.
AB  - The objective of the study was to evaluate intravenous microdialysis for
      monitoring of plasma lactate, pyruvate, glucose, creatinine, urea, adenosine,
      inosine and hypoxanthine in intensive care patients. Microdialysis probes (O.D.
      0.9 mm; membrane length 20 mm) were inserted into major veins and perfused with
      Ringer's solution. Dialysis samples were collected from 4 patients with septic
      shock in 60 min fractions during 24 h. At the end of every hour a venous blood
      plasma sample was drawn from the corresponding contralateral vein for comparison.
      Microdialysate values of all metabolites closely followed the changes in the
      corresponding blood samples. The in vivo recovery of the probe type used was
      close to 100% for lactate, creatinine, and urea, and about 90% for glucose. It is
      concluded that intravenous microdialysis sampling is a suitable method for
      continuous bedside monitoring of important metabolites in intensive care
      patients.

PMID- 8270726
TI  - Retroperitoneal hematoma may lead to overestimate nitrogen balance.

PMID- 8270727
TI  - Isoflurane sedation for critically ill patients.

PMID- 8270728
TI  - Iatrogenic-pulmonary barotrauma.

PMID- 8270729
TI  - A quantitative measure of similarity for tursiops truncatus signature whistles.
AB  - Bottlenose dolphins (tursiops truncatus) produce individually distinctive narrow
      band "signature whistles." These whistles may be differentiated by the structure
      of their frequency contours. An algorithm is presented for extracting frequency
      contours from whistles and comparing two such contours. This algorithm performs
      nonuniform time dilation to align the contours and provides a quantitative
      distance measure between the contours. Two recognition experiments using the
      algorithm on three dolphin whistles from each of five individuals classified 15
      out of 15 single-loop whistles correctly, and 14 out of 15 central loops for
      multiple-loop whistles correctly.

PMID- 8270730
TI  - Processing of spoken CVCs in the auditory periphery. I. Psychophysics.
AB  - This study provides a quantitative measure of the accuracy of the auditory
      periphery in representing prespecified time-frequency regions of initial and
      final diphones of spoken CVCs. The database comprised word pairs that span the
      speech space along Jakobson et al.'s binary phonemic features [Tech. Rep. No. 13,
      Acoustic Laboratory, MIT, Cambridge, MA (1952)]. The time-frequency domain was
      divided into "tiles" by splitting the frequency range into three bands ([0,1000],
      [1000,2500], [2500,4000]Hz), and by marking the phonemic time landmarks of the
      CVC utterance. Fourteen modified versions of this database were generated by
      introducing well-defined distortions into the time-frequency tiles (or
      combination of tiles). The performance of eight listeners was measured for each
      of these versions by using a one-interval two-alternative forced-choice paradigm,
      to minimize the role of cognition. The results demonstrate that in the first and
      the second frequency bands, the diphone information is far more important than
      the consonant information or the vowel information alone. As for the third band,
      most of the information of the diphone is contained in the consonantal time
      interval. These observations are common to both the initial and the final
      consonants of spoken CVCs. The study also provides a direct mapping between
      Jakobson et al.'s features and particular regions in the time-frequency domain.
      Voicing and nasality are strongly correlated with the diphone information in the
      first frequency band, graveness and compactness with the diphone information in
      the second frequency band, and sibilation with the consonantal time interval in
      the third frequency band.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270731
TI  - Respiratory and laryngeal measures of children during vocal intensity variation.
AB  - Simultaneous aerodynamic, acoustic, and kinematic measurements from the laryngeal
      and respiratory systems were made in order to study mechanisms for changing vocal
      intensity. Aerodynamic and acoustic measures include an approximation of open
      quotient, maximum flow declination rate, alternating glottal airflow, estimated
      tracheal pressure, sound pressure level, and fundamental frequency. Respiratory
      measures included lung volume, rib cage, and abdominal displacements. Adults were
      used as a comparison group to twenty 4-year-olds and twenty 8-year-olds.
      Laryngeal and respiratory results indicate that speech production differences
      between the children and adults are based both on size and function. For example,
      children's absolute anteroposterior diameters of the rib cage are smaller than
      adults, but their rib cage movement is larger and encompasses a different range
      during speech breathing. Since children are functionally different than adults,
      age specific speech production models need to be developed.

PMID- 8270732
TI  - An acoustic metric for assessing change in vowel production by profoundly hearing
      impaired children.
AB  - The purpose of this study was to investigate the feasibility of developing an
      acoustic metric to assess vowel production in profoundly hearing-impaired
      children. The approach taken was to develop a metric from acoustic analysis of
      vowel productions and then compare it with the perceptual ratings of the same
      productions by listeners. Speech samples were collected from three profoundly
      hearing-impaired children participating in a longitudinal study that investigated
      the effectiveness of assistive listening devices upon speech development. The
      metric used the extracted fundamental and first, second, and third formant
      frequencies to represent the tokens as points in a three-dimensional auditory
      perceptual space modeled after earlier work by Miller [J. Acoust. Soc. Am. 85,
      2114-2134 (1989)]. Euclidean distances were determined between each point and the
      intended vowel, which was represented by coordinates taken from the Peterson and
      Barney [J. Acoust. Soc. Am. 24, 175-184 (1952)] data for children. The data
      suggest that the three-dimensional metric provides significant correlations
      between production and perception.

PMID- 8270733
TI  - Two experiments on the temporal boundaries for the nonlinear additivity of
      masking.
AB  - The present paper describes the results from two experiments which explored the
      temporal boundary between overlapping and nonoverlapping maskers and its effects
      on the additivity of masking. In the first experiment, detection thresholds for a
      short-duration 1000-Hz signal were measured in the presence of two equal-duration
      broadband maskers which varied in degree of temporal overlap. Following complete
      overlap of maskers, the temporal separation of masker onsets was systematically
      varied to create conditions ranging from partially overlapping simultaneous
      masking to combined forward and backward masking. The signal was always
      temporally centered between the onset of the first masker and the offset of the
      second masker. Nonlinear additivity of masking occurred for the majority of
      subjects when maskers and signal did not overlap, whereas linear additivity
      resulted for all subjects when the maskers and signal overlapped. In the second
      experiment, two separate forward maskers were used so that masker/masker overlap
      could be manipulated independent from masker/signal overlap. Maskers were changed
      gradually from temporally overlapping, or concurrent, forward maskers to
      sequential forward maskers. Results for all subjects showed nonlinear additivity
      for all combined-masker conditions. Together, these two experiments indicated
      that nonlinear masking additivity is observed when the signal does not overlap
      temporally with the maskers. However, when maskers and signal overlap temporally
      (and spectrally), linear additivity is observed.

PMID- 8270734
TI  - The incorporation of level and level-invariant cues for the detection of a tone
      added to noise.
AB  - The potential contribution of level-dependent and level-invariant cues for the
      detection of a tone added to narrow bands of noise was assessed in two
      experiments. In the first experiment, three masker bandwidths, 40, 120, and 360
      Hz, and three center frequencies, 600, 1800, and 5400 Hz were tested. For the
      tone-in-noise detection task, the signal to be detected was a tone with a
      frequency equal to the center frequency of the noise masker. The level of the
      added tone was adjusted so as to generate d' scores of approximately 2 in a two
      alternative, forced-choice procedure. Then, the distributions of across-interval
      changes in level were measured. The distribution of differences in level was
      applied to either the noise-alone or the tone-plus-noise stimuli, allowing the
      measurement of sensitivity to changes in level for a two-interval, forced-choice
      intensity discrimination task. For one of the four observers, there was a good
      correspondence between the d' values obtained in the tone-in-noise task and the
      d' values obtained in the intensity discrimination task. For the other three
      observers, the discriminability of changes in intensity could not account for the
      detection of a tone added to noise. In order to estimate sensitivity to level
      invariant cues, the noise-alone and tone-plus-noise waveforms were scaled so as
      to present no reliable differences in level, and observers again detected which
      stimulus contained the added tone. Normalization led to d' scores smaller than
      those obtained in the initial tone-in-noise discrimination task, but performance
      levels did not fall to chance. For three of the four observers, the detection of
      a tone added to noise appeared to depend on both level and level-invariant cues.
      In a second experiment, psychometric functions were obtained for the detection of
      a tone added to noise, for the detection of changes in level associated with the
      noise-alone and the tone-plus-noise stimuli, and for the detection of a tone
      added to noise using noise-alone and tone-plus-noise waveforms with no reliable
      differences in level. The maskers were centered at 1800 Hz, and bandwidths of 40
      and 100 Hz were tested. Individual differences in detection strategy were
      obtained. Two observers appeared to rely on changes in level, one observer
      appeared to rely on level-invariant cues, and the remaining four observers
      appeared to adopt a decision strategy that integrated level and level-invariant
      cues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270735
TI  - Intensity perception. XIV. Intensity discrimination in listeners with
      sensorineural hearing loss.
AB  - Intensity discrimination of pulsed tones (also called level discrimination) was
      measured as a function of level in 13 listeners with sensorineural hearing
      impairment of primarily cochlear origin, one listener with a vestibular
      schwannoma, and six listeners with normal hearing. Measurements were also made in
      normal ears presented with masking noise spectrally shaped to produce audiograms
      similar to those of the cochlearly impaired listeners. For unilateral
      impairments, tests were made at the same frequency in the normal and impaired
      ears. For bilateral-sloping impairments, tests were made at different frequencies
      in the same ear. The normal listeners showed results similar to other data in the
      literature. The listener with a vestibular schwannoma showed greatly reduced
      intensity resolution, except at a few levels. For listeners with recruiting
      sensorineural impairments, the results are discussed according to the
      configuration of the impairment and are compared across configurations at equal
      SPL, equal SL, and equal loudness level. Listeners with increasing hearing losses
      at frequencies above the test frequency generally showed impaired resolution,
      especially at high levels, and less deviation from Weber's law than normal
      listeners. Listeners with decreasing hearing loss at frequencies above the test
      frequency showed nearly normal intensity-resolution functions. Whereas these
      trends are generally present, there are also large differences among individuals.
      Results obtained from normal listeners who were tested in the presence of masking
      noise indicate that elevated thresholds and reduced dynamic range account for
      some, but not all, of the effects of recruiting sensorineural impairment on
      intensity resolution.

PMID- 8270736
TI  - Where the action is: Weber fractions as a function of sound pressure at low
      frequencies.
AB  - Weber fractions for sound intensity were measured for 70-, 100-, 200-, 1000-, and
      10,000-Hz tone pulses at sound-pressure levels (SPLs) ranging from just above
      individual listeners' absolute thresholds to near their highest tolerable SPLs,
      using a two-alternative forced-choice adaptive staircase technique governed by a
      1-up, 3-down rule. Results for four listeners with normal hearing and varying
      experience, despite individual differences in absolute values, showed Weber
      fractions that declined as sound pressure increased above threshold and
      asymptoted at intermediate SPLs. A power function with a negative exponent
      describes the data of the individual listeners better than a logarithmic function
      does. The absolute value of the exponent of the power function, which measures
      the curvature of the function, was largest at 70 Hz and declined with increasing
      frequency, similar to how exponents of power functions relating loudness
      judgments or simple reaction time to stimulus intensity differ with sound
      frequency.

PMID- 8270737
TI  - Isolating the dynamic attributes of musical timbre.
AB  - Three experiments examined the dynamic attributes of timbre by evaluating the
      role of onsets in similarity judgments. In separate experiments, subjects heard
      complete orchestral instrument tones, the onsets of those tones, and tones with
      the onsets removed ("remainders"). Ratings for complete tones corresponded to
      those for onsets, indicating that the salient acoustic attributes for complete
      tones are present at the onset. Ratings for complete tones also corresponded to
      those for remainders, indicating that the salient attributes for complete tones
      are present also in the absence of onsets. Subsequent acoustic analyses
      demonstrated that this pattern of similarity was due to the centroid frequencies
      and amplitude envelopes of the tones. The results indicate that the dynamic
      attributes of timbre are not only present at the onset, but also throughout, and
      that multiple acoustic attributes may contribute to the same perceptual
      dimensions.

PMID- 8270738
TI  - Function-based modeling of binaural processing: level and time cues.
AB  - From theoretical considerations, function-based modeling predicts the input
      output characteristics of a neural system intended to perform a signal processing
      task within a sensory system. The sensory task under study here is the time- and
      level-based localization of a high-frequency, possibly amplitude-modulated, sound
      source in the horizontal plane. The stimulus is assumed to be represented by each
      ear's primary-like discharge pattern. An optimal system that extracts azimuthal
      angle from these discharge patterns, which represent acoustic time and level
      localization cues, has been derived. This system can be described as the
      maximization of a sum of three subsystems' outputs. The stimulus cues employed by
      these systems are interaural level difference for the level-based subsystem, the
      interaural onset-time difference for the time-based subsystem, and the interaural
      envelope-phase difference for the phase-based subsystem. The system encompassing
      all these cues is shown to trade-off the level, time, and envelope-phase cues
      depending upon the time since stimulus onset, the observation time, and the
      incident signal's level. How this system might correspond to known structures in
      the lower auditory pathway is described.

PMID- 8270739
TI  - Ear-canal impedance and reflection coefficient in human infants and adults.
AB  - The ear-canal impedance and reflection coefficient were measured in an adult
      group and in groups of infants of age 1, 3, 6, 12, and 24 months over frequency
      range 125-10,700 Hz. The development of the external ear canal and middle ear
      strongly affect input impedance and reflection coefficient responses, and this
      development is not yet complete at age 24 months. Contributing factors include
      growth of the area and length of the ear canal, a resonance in the ear-canal
      walls of younger infants, and a probable influence of growth of the middle-ear
      cavities. The middle-ear compliance is lower in infants than adults, and the
      middle-ear resistance is higher. The power transfer into the middle ear of the
      infant is much less than into that of the adult. Such differences in power
      transfer directly influence both behavioral and physiological measurements of
      hearing. The difficulties of interpretation of neonatal tympanograms are shown to
      be a consequence of ear-canal wall vibration. Impedance and reflectance
      measurements in the 2-4-kHz range are recommended as a potentially useful
      clinical tool for circumventing these difficulties.

PMID- 8270740
TI  - A comparison of transient-evoked and distortion product otoacoustic emissions in
      normal-hearing and hearing-impaired subjects.
AB  - The ability of transient-evoked otoacoustic emissions (TEOAEs) and distortion
      product otoacoustic emissions (DPOAEs) to distinguish normal hearing from hearing
      impairment was evaluated in 180 subjects. TEOAEs were analyzed into octave or one
      third octave bands for frequencies ranging from 500 to 4000 Hz. Decision theory
      was used to generate receiver operating characteristic (ROC) curves for each of
      three measurements (OAE amplitude, OAE/noise, reproducibility) for each OAE
      measure (octave TEOAEs, 1/3 octave TEOAEs, DPOAEs), for octave frequencies from
      500 to 4000 Hz, and for seven audiometric criteria ranging from 10 to 40 dB HL.
      At 500 Hz, TEOAEs and DPOAEs were unable to separate normal from impaired ears.
      At 1000 Hz, both TEOAE measures were more accurate in identifying hearing status
      than DPOAEs. At 2000 Hz, all OAE measures performed equally well. At 4000 Hz,
      DPOAEs were better able to distinguish normal from impaired ears. Almost without
      exception, measurements of OAE/noise and reproducibility performed comparably and
      were superior to measurements of OAE amplitude, although the differences were
      small. TEOAEs analyzed into octave bands showed better performance than TEOAEs
      analyzed into 1/3 octaves. Under standard test conditions, OAE test performance
      appears to be limited by background noise, especially for the low frequencies.

PMID- 8270741
TI  - Effects of contralateral acoustic stimulation on spontaneous otoacoustic
      emissions.
AB  - Spontaneous otoacoustic emissions (SOAEs) were measured in the ear canal of adult
      humans prior to, during, and following presentation of tonal and broadband
      stimuli to the contralateral ear. Tones were presented at a fixed level at ten
      frequencies relative to the SOAE. Broadband noise was presented at eight levels,
      from 6 to 76 dB SPL. Shifts in SOAE frequency and amplitude were observed for
      some subjects, for some tone conditions. Frequency shifts were always positive,
      whereas amplitude shifts were variable. No apparent pattern of tuning was seen,
      such that tones with a particular frequency relationship to the SOAEs induced
      greater changes in the SOAEs. Systematic changes in frequency and amplitude of
      SOAEs were observed for increasing level of broadband noise for all subjects.
      Results are discussed with respect to possible mechanism(s) responsible for the
      alterations in SOAEs: Transcranial conduction; the olivocochlear system; and/or
      the middle-ear reflex arc.

PMID- 8270742
TI  - Fine structure of the 2f1-f2 acoustic distortion product: changes with primary
      level.
AB  - The fine frequency structure of the 2f1-f2 acoustic distortion product (ADP fine
      structure) was examined in ten human subjects with normal hearing. Primary
      frequencies (f1 and f2) were incremented in steps of 1/32 octave with an f2/f1
      ratio of 1.2. The primary levels were kept equal to each other and varied from 45
      to 65 dB SPL in 2.5-dB steps. The results show that the ADP fine structure is
      characterized by a series of peaks and valleys across frequency, with a peak-to
      peak frequency spacing of about 3/32 octave and a peak-to-valley amplitude ratio
      of up to 20 dB. At frequencies below 4000 Hz, as primary level increases, the
      sharpness of the ADP fine structure is not significantly reduced and the pattern
      gradually shifts to lower frequencies. At frequencies above 4000 Hz, a flattening
      of the pattern is sometimes observed at high levels. A consequence of the
      underlying process responsible for the fine structure is that ADP input/output
      (I/O) functions can be highly variable in shape. Dramatic shape changes can occur
      for ADP I/O functions obtained with primary frequency changes of as little as
      1/32nd of an octave. The outward cause of I/O function variability is the
      behavior of the ADP fine structure with level; i.e., it remains robust at high
      levels and systematically shifts to lower frequencies with level. As a result,
      ADP peaks can shift to valleys with increasing level and vice versa. Thus, small
      shifts in primary frequency can result in significant changes in the shape of the
      ADP I/O function in humans.

PMID- 8270743
TI  - The effects of aging on otoacoustic emissions.
AB  - Otoacoustic emissions were measured in 42 normal hearing subjects ranging from 20
      to 80 years old. For each subject spontaneous, click-evoked, tone-burst-evoked,
      stimulus frequency and distortion product emissions were measured across a wide
      intensity range for frequencies between 1 and 3 kHz. Although there are
      significant differences between age groups, the results indicate no age effect
      independent of hearing sensitivity on any type or parameter of otoacoustic
      emissions (OAE). The effect of increasing age is confounded with the effect of
      decreasing sensitivity such that post hoc analyses are inadequate to separate the
      effects of sensitivity and age on otoacoustic emissions. Even within the range of
      audiometrically normal hearing, OAE characteristics vary with threshold for all
      age groups. The conclusion is that hearing sensitivity must be included as a
      controlled variable in order to accurately assess intrinsic aging effects.

PMID- 8270744
TI  - A computational model of echo processing and acoustic imaging in frequency
      modulated echolocating bats: the spectrogram correlation and transformation
      receiver.
AB  - The spectrogram correlation and transformation (SCAT) model of the sonar receiver
      in the big brown bat (Eptesicus fuscus) consists of a cochlear component for
      encoding the bat's frequency modulated (FM) sonar transmissions and multiple FM
      echoes in a spectrogram format, followed by two parallel pathways for processing
      temporal and spectral information in sonar echoes to reconstruct the absolute
      range and fine range structure of multiple targets from echo spectrograms. The
      outputs of computations taking place along these parallel pathways converge to be
      displayed along a computed image dimension of echo delay or target range. The
      resulting image depicts the location of various reflecting sources in different
      targets along the range axis. This series of transforms is equivalent to
      simultaneous, parallel forward and inverse transforms on sonar echoes, yielding
      the impulse responses of targets by deconvolution of the spectrograms. The
      performance of the model accurately reproduces the images perceived by Eptesicus
      in a variety of behavioral experiments on two-glint resolution in range, echo
      phase sensitivity, amplitude-latency trading of range estimates, dissociation of
      time- and frequency-domain image components, and ranging accuracy in noise.

PMID- 8270745
TI  - Radiation pattern of a focused transducer: a numerically convergent solution.
AB  - The radiation pattern of a focused transducer is reexamined. The radiation field
      is divided into an illuminated zone and a shadow zone. A numerically convergent
      solution of the pressure distribution in terms summations of Bessel functions is
      provided. This solution is computationally more advantageous than earlier results
      where a double or single integral in the complex plane is required. The pressure
      amplitude differs from earlier reports slightly for off-axis locations at low
      frequency. This difference may have significance for backscatter coefficient
      determination where scatterers are assumed present over a time-gated volume. The
      solution for a flat disk radiator is obtained as a limiting case.

PMID- 8270746
TI  - Low-frequency sound detection by a bottlenose dolphin.

PMID- 8270747
TI  - Intelligibility-weighted measures of speech-to-interference ratio and speech
      system performance.

PMID- 8270748
TI  - The quasisteady approximation in speech production.

PMID- 8270749
TI  - Block vs Willett: a debate on the validity of food frequency questionnaires.

PMID- 8270750
TI  - Professional demand for dietitians and nutritionists in the year 2005.

PMID- 8270751
TI  - Military RDs improve oral liquid diets. How to ensure nutritious meals for
      patients with maxillofacial and oral injuries.

PMID- 8270752
TI  - Clinton's Health Security Act recognizes value of nutrition: an update on the
      legislative debate over health care reform.

PMID- 8270753
TI  - 5 a day for better health: a new research initiative.

PMID- 8270754
TI  - Physicians' implementation of dietitians' recommendations: a study of the
      effectiveness of dietitians.
AB  - OBJECTIVE: To determine how often dietitians' recommendations were implemented by
      physicians and to identify workplace and demographic factors that correlated with
      successful implementation of recommendations. DESIGN: A cohort of hospitals was
      surveyed by mail. Dietitians recorded recommendations written in five consecutive
      medical record entries and sent them to the chief clinical dietitian. Seventy-two
      hours later, physicians' order sheets were reviewed to assess implementation.
      Dietitians completed demographic questionnaires. SUBJECTS: Forty-four general
      hospitals in Philadelphia and the surrounding area were surveyed. To ensure
      similar standards of nutrition care, only hospitals approved by the Joint
      Commission on Accreditation of Healthcare Organizations were selected.
      STATISTICAL ANALYSIS PERFORMED: chi 2, Fisher's exact test, and the Kruskall
      Wallis test were used to correlate demographic variables with implementation
      rate. MAIN OUTCOME MEASURE: Implementation of the dietitians' recommendations by
      physicians' orders. RESULTS: Responses were obtained from 35 of the 44 hospitals
      and 98 (70%) of the clinical dietitians. Of the 865 recommendations, 42% were
      implemented. Significantly higher implementation rates were noted for
      recommendations solicited by (50%) or discussed with the physician (65%).
      Dietitians were more successful in teaching hospitals and when they reported to a
      hospital-operated foodservice rather than a contract foodservice. Success
      correlated with a lower workload when measured by the ratio of admissions to
      staff but not when measured by the ratio of beds to staff. CONCLUSIONS:
      Dietitians could have a greater effect on nutrition care by discussing
      recommendations with physicians. Further research is needed about staffing
      formulas and methods to improve the effectiveness of dietitians.

PMID- 8270755
TI  - Dietary assessment of patients with chemosensory disorders.
AB  - OBJECTIVE: To identify individuals who are at nutritional risk because of taste
      and/or smell disorders. DESIGN: Patients referred by a private physician for
      evaluation of a chemosensory complaint underwent an extensive battery of taste
      and smell tests, otorhinolaryngologic tests, and, in some cases, periodontal
      examinations and completed a dietary/health questionnaire, a 24-hour recall, and
      a 2-day diet record. SETTING: Patients were interviewed at the Monell-Jefferson
      Chemosensory Clinical Research Center, Philadelphia, Pa. SUBJECTS: We studied 310
      patients (142 men and 168 women) with a primary complaint of chemosensory
      disorder. Mean age was 50.5 +/- 15.7 (range = 15 to 93 years). Normative data
      were provided by an additional 79 healthy control subjects (42 men and 37 women)
      with no taste or smell complaint. Their mean age was 48.8 +/- 18.8 years (range =
      20 to 83 years). MAIN OUTCOME MEASURES: Chemosensory disorder-related changes in
      food habits (determined by questionnaire responses), nutrient intake (analysis of
      3-day food records), and body weight (self-reported). STATISTICAL ANALYSES:
      Analysis of covariance, followed by post hoc analysis of adjusted means with the
      Tukey honestly significant difference test, was used to explore group differences
      in nutrient intake and body weight. chi 2 Analysis and the Pearson correlation
      coefficient were used to evaluate relationships between variables. RESULTS: When
      groups were classified according to chemosensory diagnosis, group differences
      were observed on global appetitive questions, but complaints were high in all
      groups. Approximately 65% (203 of 310) of patients had self-reported body weights
      within 5% of their predisorder weight, but clinically meaningful weight gains or
      losses were observed in each group. Patients with multiple chemosensory disorders
      were most likely to lose weight, whereas the incidence of weight gain was highest
      in patients with anosmia. Patient report of a change in eating patterns was the
      best predictor of weight change among the variables examined. CONCLUSIONS:
      Dietary responses to chemosensory disorders vary widely and may place patients at
      nutritional risk. Until better prognostic indexes are identified, dietitians
      should query patients about disorder-related alterations in eating patterns and
      provide appropriate individualized counseling.

PMID- 8270756
TI  - Diet quality index: capturing a multidimensional behavior.
AB  - OBJECTIVE: Data for 5,484 adults (aged 21 years and older) who participated in
      the 1987-88 Nationwide Food Consumption Survey (NFCS) were used to develop an
      index of overall dietary intake that related to the major, diet-related, chronic
      diseases in the United States. The low response rate of the 1987-88 NFCS has
      raised concerns about potential bias, but this large data set is useful for
      methodologic studies and research that does not attempt to generalize the results
      to the US population. ANALYSES: Dietary recommendations from the 1989 National
      Academy of Sciences publication Diet and Health were stratified into three levels
      of intake for scoring. Individuals who met a dietary goal were given a score of
      zero. Those who did not meet a goal, but had a fair diet, were given one point,
      and those who had a poor diet were given two points. These points were summed
      across eight diet variables to score the index from zero (excellent diet) to 16
      (poor diet). RESULTS: Lower index scores were positively associated with high
      intakes of other important measures of diet quality (eg, fiber, vitamin C). We
      found that single nutrients (such as dietary fat) were not necessarily associated
      with other measures of diet quality. CONCLUSION: We concluded that this index
      ranking of overall dietary patterns was reflective of total diet quality, though
      substantial misclassification can result from using single nutrients or foods as
      indicators of diet quality.

PMID- 8270757
TI  - Cholesterol-lowering effect of barley bran flour and oil.
AB  - OBJECTIVE: To compare the effects of adding barley bran flour and a barley oil
      extract to a fat-modified diet on serum lipids in persons with
      hypercholesterolemia. DESIGN: The basic design of the study was a randomized, 30
      day intervention trial. It included a neutral-fiber control group and a 1-week
      preintervention period for the collection of baseline data. SUBJECTS: The
      subjects were 79 men and women with hypercholesterolemia. Subjects had a mean age
      of 48.2 years, and all completed the study. INTERVENTION: All participants were
      instructed to follow the National Cholesterol Education Program (NCEP) step 1
      diet and were randomly assigned to one of three treatment groups: 20 g added
      cellulose, 3 g added barley oil extract, or 30 g added barley bran flour. MAIN
      OUTCOME MEASURES: Total serum cholesterol, high-density lipoprotein cholesterol
      (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very-low-density
      lipoprotein cholesterol were measured, along with serum triglycerides, before the
      intervention, at week 1, at week 3, and at the end of the intervention.
      STATISTICAL ANALYSES PERFORMED: Student's paired t test was used to detect
      significant changes within each treatment group from baseline to the end of the
      30-day intervention. In addition, Pearson's correlation coefficients were used to
      detect significant correlations between the variables measured. RESULTS: Addition
      of barley bran flour significantly (P = .0001) decreased total serum cholesterol
      (-0.60 mmol/L) as did addition of barley oil (-0.50 mmol/L; P = .002) after 30
      days of intervention. Similarly, LDL-C decreased 6.5% with addition of barley
      bran flour (P = .036) and 9.2% with addition of barley oil (P = .003). Total
      serum cholesterol or LDL-C of the cellulose control group did not decrease
      significantly over the same period. HDL-C decreased significantly in the
      cellulose control group and the barley bran flour group (-0.15 mmol/L, P = .012,
      and -0.15 mmol/L, P = .006, respectively), but not in the barley oil group.
      CONCLUSION: We conclude that addition of barley bran flour or barley oil enhances
      the cholesterol-lowering effect of the NCEP step 1 diet in individuals with
      hypercholesterolemia.

PMID- 8270758
TI  - Management dilemmas in the individual with cystic fibrosis and diabetes.
AB  - As their life expectancy has improved, patients with cystic fibrosis (CF) have
      experienced an increasing incidence of diabetes. Hyperglycemia may adversely
      influence weight, pulmonary function, and development of microvascular
      complications. Strict control of blood glucose has not universally been sought,
      however. A program of multiple daily insulin injections and self-monitoring of
      blood glucose with an aim of normoglycemia is described in this article. The
      typical cystic fibrosis diet is variable in quantity and features a preponderance
      of simple carbohydrates; this is contrary to the usual diabetes meal plan. We
      describe the use of a flexible meal-planning system to establish individualized
      carbohydrate targets with specific insulin boluses titrated to each meal to
      control postprandial blood glucose excursions. Records of 22 patients followed
      for more than 1 year are reviewed. Mean (+/- standard error of the mean)
      glycosylated hemoglobin was reduced from 11.3 +/- 3.1% (at baseline) to 8.1 +/-
      1.8% (at 1 year). Mean percent of ideal body weight also increased from 95.4 +/-
      15.2 to 100 +/- 17.1. We conclude that strict metabolic control is an attainable
      goal in patients with cystic fibrosis and is associated with positive weight
      gain.

PMID- 8270759
TI  - Dietitians' disease-specific nutrition care planning strategies.

PMID- 8270760
TI  - Utilization of home health care services in HIV infection: a pilot study in Ohio.

PMID- 8270761
TI  - Addition of pectin and temperature influence the viscosity of some tube-feeding
      formulas.

PMID- 8270762
TI  - Energy intake, body weight, and lean body mass are maintained in healthy, active
      women consuming a US Space Shuttle diet.

PMID- 8270763
TI  - Gamma aminobutyric acid radioreceptor-assay a possible biomarker for human
      exposure to certain agrochemicals.
AB  - Cyclodiene insecticides, hexachlorocyclohexanes, pyrethroids, bicyclophosphates,
      the bicycloorthocarboxylate insecticides and some of their metabolites and
      environmental degradation products are central nervous system toxicants with high
      specific binding affinity to the chloride channel of the gamma-aminobutyric acid
      (GABA)A receptor-ionophore sites. [35S] tertiary-butylbicyclophosphorothionate
      (TBPS) with specific activity higher than 60 Ci/mmole has a high binding affinity
      to the same sites and is now commercially available and can be used to label the
      GABAA receptor for the development of a radioreceptor assay technique. The GABA
      receptor was prepared by ultra centrifugation and dialysis of brain homogenates
      of either cow, goat, rat or catfish. The receptor was then labeled with [35S]
      TBPS and the assay was conducted by measuring the displacement of radioactivity
      following incubation with samples containing the analytes. A radioreceptor assay
      protocol was developed to measure the amount of the alpha-endosulfan in blood
      samples. The assay was extremely sensitive, and can detect 0.2 nM of endosulfan
      at a level equivalent to 0.08 ppb or 8 x 10(-11) gm of endosulfan in each ml of
      the blood samples.

PMID- 8270764
TI  - Toxicological potential of malathion residues in stored soybean seeds.
AB  - Succinate-14C-malathion penetrates readily into soybean seeds. The total internal
      residues inside the seeds amounted to 58-65% of the applied dose after 30 weeks,
      of which 8-9% were in the form of bound residues. The major part of the internal
      methanol extractables are chloroform soluble metabolites which include malathion
      (about 60%), monocarboxylic acid (15%) and its decarboxylation product (8%). The
      water soluble metabolites contained only one radioactive substance, namely
      malathion dicarboxylic acid. The toxicological potential of the total internal
      residues was studied by feeding mice with the washed seeds for about 2.5 months.
      Treated mice suffered from deterioration of hepatic and renal function as
      indicated by the observed increased level of blood serum esterases and blood urea
      nitrogen. The results of blood biochemistry are supported by the
      histopathological changes observed in the liver, kidney, stomach and intestine.
      The organs showed degenerative changes including leucocytic aggregation,
      congestion and dilatation of blood vessels. Other adverse effects caused by
      malathion residues are indicated from cytogenetic studies on bone marrow of
      treated mice. Studies showed an initial bone marrow toxicity as indicated by
      increase in percentage of polychromatic erythrocytes over controls. This effect
      diminished upon prolongation of feeding period over one month. Feeding with
      malathion residues affected a gradual increase, with feeding period, in the
      percentage of polychromatic erythrocytes with micronuclei, a parameter
      recommended for detecting chemical mutagenes in animal test systems.

PMID- 8270765
TI  - Aluminum interaction with human brain tau protein phosphorylation by various
      kinases.
AB  - Phosphorylation is an indispensable process for energy and signal transduction in
      biological systems. AlCl3 at 10 nM to 10 microM range activated in-vitro [gamma
      32P]ATP phosphorylation of the brain (tau) tau protein in both normal human or E.
      coli expressed tau forms; in the presence of the kinases P34, PKP, and PKC.
      However, higher concentrations of ALCl3 inhibited the tau phosphorylation with
      P34, PKP, and PKC to a maximum at 1 mM level. AlCl3 at 100 microM to 500 microM
      range induced non-enzymatic phosphorylation of tau with gamma-ATP, gamma-GTP, and
      alpha-GTP. AlCl3 activated histone phosphorylation by P34 in a similar pattern.
      The hyperphosphorylation of tau by Al3+ was accompanied by molecular shift and
      mobility retardation in SDS-PAGE. This may demonstrate the mechanism of the
      longterm neurological effect of Al3+ in human brain leading to the formation of
      the neurofibrillary tangles related to Alzheimer's disease.

PMID- 8270766
TI  - 6th Meeting of the European Neuroendocrine Association. Lisboa, Portugal, October
      6-9, 1993. Abstracts.

PMID- 8270767
TI  - Inheritance of renal amyloidosis in Chinese Shar-pei dogs.
AB  - Renal amyloidosis (RA) and recurrent fever of unknown origin (RFUO) are
      characteristics of familial Mediterranean fever (FMF), a human disorder inherited
      as an autosomal-recessive trait. Although no animal model has been established
      for FMF, a similar syndrome of RFUO and RA has been reported in Chinese Shar-pei
      (CSP) dogs. This report addresses two questions: (1) Is RA inherited in CSP dogs?
      (2) If it is, is it possible to hypothesize the type of inheritance involved? Two
      studies were conducted to answer these questions: a historical cross-sectional
      comparison, which included CSP and non-CSP dogs with RA; and a prospective study
      that included CSP dogs with RA, RFUO, or both. The cross-sectional comparison
      resulted in an odds ratio of 10 for RA in CSP dogs under 7 years of age. The
      prospective study of 28 dogs with RA or RFUO identified 20 that had RFUO and RA,
      three with RA alone, and five with RFUO alone. RFUO preceded RA in all cases with
      both conditions. The RFUO/RA combination was observed in both sexes. Four dogs
      with RFUO with or without RA were born to parents that either were alive at age 7
      or had died because of conditions other than kidney failure/RA. When one parent
      was known to express one of these conditions, the prevalence of RA was between
      25% and 50% among littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270768
TI  - Origin of late lactation protein from beta-lactoglobulin in the tammar wallaby.
AB  - Two of the dominant whey proteins of the tammar wallaby, beta-lactoglobulin (BLG)
      and late lactation protein (LLP), have been positively identified on gradient
      polyacrylamide gradient gels by N-terminal protein sequencing. The origin of the
      electrophoretic variation present in these proteins has been found to be
      principally genetic. The variation was examined in 97 lactating female tammar
      wallabies, of which 10 were followed throughout lactation to determine if any
      developmental variation existed. The only distinguishable developmental
      difference results from the previously described appearance of LLP at the
      beginning of phase III of lactation (approximately 180 days after birth of the
      young). Electrophoretic analysis of BLG implies that it exists in monomeric,
      dimeric, and tetrameric forms. Very strong linkage disequilibrium, indicative of
      close linkage, was found between alleles at the Blg and Llp loci. Examination of
      their cDNA sequences suggests that LLP and BLG represent an ancient gene
      duplication. Both have conserved amino acid residues characteristic of the
      lipocalins. The results imply that the marsupial mode of lactation, and hence of
      reproduction, is also very ancient.

PMID- 8270769
TI  - Synergistic interactions between two skeletal mutations in mice: individual and
      combined effects of the semidominants cleidocranial dysplasia (Ccd) and short
      digits (Dsh).
AB  - Heterozygotes for cleidocranial dysplasia (Ccd) and short digits (Dsh) were
      crossed to test whether synergistic interactions occur between different dominant
      mutations whose individual pleiotropic phenotypic effects exhibit a common
      feature. These unlinked mutations are homozygous lethal, and they are congenic on
      the C57BL/10 background. Each mutation caused more than 10 different anomalies
      and showed variable expressivity. Each mutation produced several malformations
      that were present in every heterozygote. Seven different synergistic interactions
      were found, including one that yielded an entirely new abnormality not predicted
      from any abnormalities found in either of the single heterozygotes. Although
      synergistic interactions between dominant mutations have not, to our knowledge,
      been described in humans, these findings in mice increase the probability that
      they occur in humans. Under certain circumstances in human populations, the
      segregation of mutations causing synergistic interactions of the type
      demonstrated might be confused with recessive inheritance. It will be important
      to learn whether synergistic interactions can occur between other mutations. If
      they can, it will probably become important to take synergistic interactions into
      account when estimating the genetic hazards to humans from mutagens. Three
      antagonistic interactions were also found.

PMID- 8270770
TI  - Morphological mutant in the entomopathogenic nematode, Heterorhabditis
      bacteriophora.
AB  - Heterorhabditis bacteriophora is an entomopathogenic nematode that has potential
      as a biological control agent. As a first step in the genetic analysis of this
      nematode, we induced and isolated a short nematode (dumpy) from the F2 progeny of
      an EMS mutagenized nematode. Phenotypically, the dumpy adult is 60% shorter than
      the wild type. There is almost no longitudinal growth after the infective
      juvenile stage. Dumpy is completely recessive with 100% penetrance and uniform
      expressivity. When F1 progeny were allowed to self, F2 progeny segregated wild:
      dumpy in a 15:1 ratio (chi 2 = 0.634, .5 > P > .2). This dumpy mutation (Rhdpy)
      complements another dumpy mutation isolated in Israel and is the second gene
      known for this species.

PMID- 8270771
TI  - Chromosomal polymorphism in sand gazelles (Gazella subgutturosa marica).
AB  - A total of 84 Gazella subgutturosa from three captive populations (two in Saudi
      Arabia, one in Qatar) were karyotyped. The number of chromosomes is 33, 32, or 31
      for the males and 32, 31, or 30 for the females because of the X-autosome
      translocation that is common in the genus and a centric fusion between the two
      pairs of acrocentric chromosomes. The G- and R-banded karyotypes of gazelles
      translocated show that this fusion is the same as that previously reported for
      gazelles from Jordan. The precise origin of these populations is not known, but
      in every case the first animals are said to come from the wild in Saudi Arabia.
      This chromosomal translocation appears to be a populational polymorphism and not
      the result of hybridization between two different subspecies of G. subgutturosa.

PMID- 8270772
TI  - The R- and G-banded karyotypes of the sable antelope (Hippotragus niger).
AB  - The karyotype of the sable antelope has been investigated by RBG- and GTG-banding
      techniques. Chromosome preparations were made from peripheral blood lymphocytes,
      and primary fibroblast cells were cultured from skin biopsies. The RBG-banded
      chromosomes were identified and classified according to the standard conventions
      used for cattle and goat. The diploid number of the sable antelope is 60. The
      autosomes are all acrocentric, the X is a large acrocentric, and the Y is a
      minute acrocentric. Comparison of banding patterns in sable antelope and cattle
      chromosomes reveals the existence of a high degree of homoeology except for at
      least one pair of autosomes and the X chromosome.

PMID- 8270773
TI  - Labs limit testing as result of CLIA. Interview by Bob Carlson.

PMID- 8270774
TI  - Clinton health reform plan promises universal access.

PMID- 8270775
TI  - Medicaid issue fades as legislative concern.

PMID- 8270776
TI  - Digest of health and medical laws. 1993 Indiana General Assembly.

PMID- 8270777
TI  - Limited liability company new option for physicians.

PMID- 8270778
TI  - Limited screening echocardiography in athletic exams: economic and administrative
      aspects.

PMID- 8270779
TI  - Surgical management of ventricular tachycardia.
AB  - Advances in portable high-speed computer technology have allowed intraoperative
      mapping of the ventricular endocardium. Accurate and highly precise endocardial
      maps have rendered certain types of ventricular tachycardia curable. This article
      discusses the options available to patients with ventricular tachycardia and
      places special emphasis on high-speed precision mapping and endocardial resection
      for cure.

PMID- 8270780
TI  - Maternal mortality in Indiana: a report of maternal deaths in 1991.

PMID- 8270781
TI  - From the museum.

PMID- 8270782
TI  - Maturation of the dopamine innervation during postnatal development of the
      prefrontal cortex in gerbils (Meriones unguiculatus). A quantitative
      immunocytochemical study.
AB  - Dopamine (DA)-immunoreactivity was investigated in the prefrontal cortex of
      gerbils (Meriones unguiculatus). For that purpose, a sensitive and selective
      antibody against glutaraldehyde-conjugated dopamine was applied. All detectable
      fragments of dopamine-immunoreactive nerve fibres were identified in selected
      consecutive frontal sections and their total length was determined in both the
      medial and orbital prefrontal cortex on postnatal days 7, 14, 23, 30, 60, and 90.
      Dopamine immunoreactivity revealed exponential growth until postnatal day 30, and
      further increased until postnatal day 90 with reduced increments. Due to higher
      initial percentage growth rates the dopamine innervation in the orbital
      prefrontal cortex achieved maturity earlier than in the medial prefrontal areas.
      Quantitative maturation of the prefrontal DA innervation is discussed with
      current data on functional and structural development of the prefrontal cortex.

PMID- 8270783
TI  - Astrocyte-regulated GABA-ergic striatal neurons development: an in vitro
      ultrastructural study.
AB  - Striatal neurons from E15 rat embryos were dissociated, plated at low cell
      density on polyornithine or on astrocyte monolayers derived from the striatum
      (homotopic) or mesencephalon (heterotopic), and cultured in a chemically defined
      medium. After 2 to 10 days neurons could be divided in 3 classes according to
      their cell body diameter: small, medium or large. The percentage of small neurons
      which was very high 60% for GABAergic neurons on polyornithine after 2 days in
      vitro was reduced to 35% on mesencephalic astrocytes and to less than 20% on
      striatal astrocytes. The decrease in the number of small cells was paralleled by
      an increase in the number of multipolar medium size cells whereas the percentages
      of bipolar medium size and large neurons remained constant (55 and 4%
      respectively). All results obtained with the general neuronal population were
      replicated with the GABAergic sub-population which accounted for more than 50% of
      total neuronal population. These experiments confirm the beneficial influence of
      homotopic astrocytes on neuronal differentiation and on dendrite growth.

PMID- 8270784
TI  - Distribution of GABAergic synapses and their targets in the dentate gyrus of rat:
      a quantitative immunoelectron microscopic analysis.
AB  - The dentate gyrus has been shown to receive a laminated and target selective
      GABAergic input (Han et al., 1993; Halasy and Somogyi, 1993), but the numerical
      parameters of this innervation are not known. In order to establish the relative
      weight of GABAergic inputs to the dendritic versus somatic regions of granule
      cells the numerical density and proportion of GABA-immunopositive and
      immunonegative synaptic boutons and their postsynaptic targets were determined in
      the molecular and granule cell layers of the dentate gyrus using the
      postembedding immunogold method. The granule cell layer contained 9% of all
      synapses with the remaining 91% being in the molecular layer. Altogether 17% of
      all synaptic boutons were GABA-immunoreactive, and they formed either type 1 or
      type 2 synaptic junctions. About 88% of synaptic boutons in the granule cell
      layer and 7-8% in the molecular layer were GABA-positive. However, the numerical
      density (number of synapses per unit volume) of GABA-immunoreactive type 2
      synapses was calculated to be only slightly less in the molecular layer than in
      the granule cell layer (100 x 10(6)/mm3 tissue in the granule cell layer and
      about 86 x 10(6)/mm3 in the molecular layer). In addition, GABA-positive type 1
      synapses were found in lower number at the border region of the two layers. The
      mean volume of the molecular layer of the dentate gyrus in the Wistar rat was
      calculated to be nearly 4 times larger than the volume of the granule cell layer
      (West and Andersen, 1980). This means that 25-26% of all GABAergic type 2
      synapses are located in the granule cell layer, and 74-75% in the molecular
      layer. The mean postsynaptic targets of the GABA-immunoreactive boutons in the
      granule cell layer were granule cell somata (46-60%), followed by dendritic
      shafts (26-29%), spines (up to 14%), and axon initial segments (7-9%). In the
      molecular layer the dominant postsynaptic targets of GABAergic synapses were
      dendritic shafts (63-72%), followed by dendritic spines (26-37%). About 2-3% of
      the targets of all GABA-immunoreactive synapses were GABA-immunoreactive
      dendritic shafts or somata. Up to 98% of all GABA-immunonegative synaptic boutons
      were found in the molecular layer, most of them terminating on dendritic spines.
      These results show that the dendritic region of the granule cells provides sites
      for GABAergic inhibition which in quantitative terms highly outnumber the somatic
      region in the dentate gyrus.

PMID- 8270785
TI  - The ultrastructural organization of the nucleus of the posterior commissure of
      rat.
AB  - An electron microscope study was carried out to clarify the ultrastructure of the
      nucleus of the posterior commissure (NPC) of rat which is thought to be related
      to the eye movements and oculomotor reflexes. The neurons were small or medium
      sized, loosely arranged in an extensive neuropil. The nerve cell bodies showed a
      high nucleocytoplasmatic ratio, scanty endoplasmic reticulum and very few axo
      somatic contacts. The synaptic boutons were very numerous in the neuropil, thus
      indicating the latter as the main target for inputs to the NPC. The majority of
      the synapses showed the typical morphological features of the excitatory synapses
      and so it was hypothesized that a mainly excitatory activity takes place in the
      NPC. Since the NPC, together with the nucleus of Darkschewitsch (ND) and the
      interstitial nucleus of Cajal (INC) belongs to the accessory oculomotor nuclei, a
      comparison of their ultrastructure was carried out.

PMID- 8270786
TI  - Two types of neuronal precursor cells in the mammalian retina--a short review.
AB  - This short review summarizes current evidence that the mammalian retina is
      populated by two distinct groups of retinal neurons. One of them (ganglion cells,
      cone photoreceptor cells, horizontal cells, and a subpopulation of amacrine
      cells) is generated early in ontogenesis, and may be phylogenetically old. The
      other group (rod photoreceptor cells, bipolar cells, and another subpopulation of
      amacrine cells) is born late in ontogenesis, and seems to have been acquired
      later in phylogeny. It is suggested that the two groups of neurons are generated
      by two different types of precursor cells that may result from an asymmetrical
      final division of the undifferentiated retinal stem cells. Qualitative and
      quantitative features of precursor cell proliferation and differentiation are
      discussed.

PMID- 8270787
TI  - Treatment with cyclosporine A promotes axonal regeneration in rats submitted to
      transverse section of the spinal cord.
AB  - The abortive axonal regeneration in the central nervous system (CNS) of mammals
      has been attributed to a series of inhibitory factors. Previous reports suggest
      the development of autoimmune reactions following CNS lesion in mammals. In this
      study we investigated whether immunosuppressive treatment with cyclosporine A is
      able to facilitate axonal regeneration in rats submitted to complete transverse
      section of the spinal cord at the level of T7-T8. Treated animals received daily
      subcutaneous injections of cyclosporine A (2.5 mg/kg), while control rats were
      given a similar treatment with saline. Immunosuppression was begun immediately
      after spinal cord transection. Strong evidence of morphological axonal
      regeneration was observed 15 days after surgery in all cyclosporine A treated
      animals. Furthermore, treatment with cyclosporine A markedly reduced the seric
      immune reaction elicited by the lesion. The results of this study, although
      preliminary, provide further evidence for the development of autoimmune processes
      following lesion in the CNS, and suggest that blocking of the immune reaction
      facilitates axonal regeneration in the rat.

PMID- 8270788
TI  - Influence of seasonal adaptation on the distribution of cytochemically detectable
      endogenous calcium in synaptic terminals of the optic tectum of crucian carp
      (Carassius carassius L.).
AB  - Crucian carps were seasonally adapted to high (23 degrees C) or low (4 degrees C)
      temperatures and synaptic regions in the optic tectum were analyzed by means of
      energy-filtering transmission electron microscopy (EFTEM). The amount of
      cytochemically detectable endogenous calcium in synaptic clefts was quantified by
      means of image analysis and the amount of glycogen granules in synaptic regions
      was assessed. In cold-adapted fish, glycogen is increased, especially in glial
      cells, while the calcium-containing precipitates are reduced. This is interpreted
      as a characteristic feature of inactive synapses, in which glycogen accumulates
      and in which the calcium turnover is slowed down. Short-term thermal stress did
      not influence the amount of calcium or glycogen.

PMID- 8270789
TI  - Morphogenetic differentiation of the brain of the cichlid fish, Oreochromis
      mossambicus.
AB  - In the present study, the morphogenetic brain differentiation of the cichlid
      fish, Oreochromis mossambicus, is described using conventional histological
      methods. Cross sections through the developing brain of fish larvae aged 2, 8,
      10, 12 and 20 days post hatch, and of adults, were investigated in order to
      characterize individual brain regions and nuclei, especially parts of the
      diencephalon, brainstem and cerebellum during critical phases of early larval
      development. The above age stages conform to the following developmental (larval)
      stages: 2 days = stage 7, 8 days = stage 10, 10 days = stage 11, 12 days = stage
      12 and 20 days = stage 15. An increasing number of nuclei and a volumetric
      increase in size of individual brain parts in older fish larvae and in adult fish
      were registered. In the optic tectum, an extreme lateral extension was found in
      contrast to an insignificant increase in stratification at this developmental
      time. In one part of the brainstem, the Area octavolateralis (AOL) of 2-day-old
      larvae, only a few undifferentiated perikarya were found and in the AOL of 20-day
      old animals up to 5 nuclei, versus 7 AOL-nuclei in adult fish brain, could be
      discriminated. Variations in the position of the Mauthner cell versus the
      surrounding and corresponding brain nuclei were shown during the ontogenetic
      development. The results were presented by cartoon portrayals of the
      relationships between characteristic nuclei and by drawings of specific brain
      cross sections in different aged larval stages.

PMID- 8270790
TI  - How the myelin picture of the human cerebral cortex can be computed from
      cytoarchitectural data. A bridge between von Economo and Vogt.
AB  - In the cerebral cortex two main types of anatomical parcellation have been
      proposed: cyto- and myeloarchitectonics. Cytoarchitectonics is based on
      differences in the distribution and the sizes of cell bodies. Myeloarchitectonics
      relies on the layering and packing density of intracortical myelinated fibres.
      Thereby attention is mainly focused on those horizontal fibres which are
      organized in bands known as the stripes of Baillarger. Cyto- and
      myeloarchitectonics must be somehow related: structural changes from area to area
      as revealed by the Nissl stain coincide with changes in the myelin picture. In
      this paper, it is demonstrated that two simple assumptions are sufficient to
      transform quantitative data on the Nissl picture of a certain area (i.e. layer
      thicknesses, neuron sizes, neuron densities) into the corresponding myelin
      picture. The first assumption is that large neurons contribute more to the
      intracortical myelin content than small ones, and that this relation can be
      represented by a sigmoid curve. The second assumption is that the average
      distribution of horizontal axon collaterals of pyramidal neurons with respect to
      the cell body can be quantified by a simple model. On the basis of these two
      assumptions, myelin patterns were computed for the whole spectrum of cortical
      variability, including the primary visual, somatosensory, auditory and motor
      cortices, the speech centres and a number of association areas. Comparison of the
      simulations with real myelin preparations revealed remarkable similarities. These
      findings support the assumption that the horizontal component of the myelin
      picture is mainly produced by axon collaterals of pyramidal cells, and that
      nonpyramidal neurons and afferent fibres play a minor role. Moreover, the results
      suggest that the distribution of horizontal axon collaterals of pyramidal neurons
      and the principles of their myelination are very similar in different areas. The
      function of intracortical myelin is discussed. The increase in conduction
      velocity gained by myelination seems negligible for most intracortical fibres. It
      is argued that myelination may be related to learning processes during the
      critical period.

PMID- 8270791
TI  - Optic tectum in congenitally monophthalmic fishes and chicks.
AB  - Morphometry of optic tectum layers was performed in fishes and birds that were
      congenitally monophthalmic (or had one very small or malformed eye). The optic
      chiasm was studied with regard to possible anomalies of the fiber distribution.
      In two very young fish larvae with only one ocular rudiment, no differences were
      found between the two tecta. In fishes and chicks with one normal and one eye of
      reduced size, the volume of superficial tectal layers contralateral to the small
      eye was significantly more affected (reduction by 40 to 70%) than that of the
      deep layers (reduction by 10 to 30%). Particularly pronounced differences between
      the superficial tectal layers of both sides were found in a fish where a thin
      optic nerve, originating in an unusually small eye, projected to the ipsilateral
      side of the brain. It is concluded that (1) the development of superficial tectal
      layers depends more strongly on optic innervation than that of deep layers; (2)
      obvious differences between tecta with and without optic innervation develop
      rather late in ontogeny; (3) there seems to be no measurable difference between
      effects of a poor (less than 25%) innervation of the tectum and a complete lack
      of this projection.

PMID- 8270792
TI  - Distribution pattern of c-Fos expression induced by sciatic nerve sectioning in
      the rat central nervous system.
AB  - c-Fos expression in the rat central nervous system following sciatic nerve
      section was compared using an immunohistochemical procedure with control skin
      incisions. c-Fos-immunoreactive (IR) materials were localized in the nuclei of
      nerve cells, and these positive cells were most abundantly observed 120 min after
      the operation. In the spinal cord, c-Fos-IR cells were seen in the posterior horn
      on the operated, but not in the contralateral side. The anterior horn and the
      dorsal root ganglia did not contain c-Fos-IR cells. The experimental animals had
      the largest number of c-Fos-IR cells in the lumbosacral segments, especially in
      laminae I and II of L4 and L5 segments. The difference in the number of c-Fos-IR
      cells and IR intensity between the experimental and control animals was
      conspicuous in the lumbosacral segments, but there was no significant difference
      between them in the cervical and thoracic segments. In the brain, an apparent
      difference in positive cell distribution was not recognized between the
      experimental and control animals. c-Fos-IR cells were observed in various regions
      of the brain. A high concentration of positive cells was seen in the temporal
      cortex, the clastrum, the lateral septal nucleus (ventral part), the hypothalamic
      nuclei such as periventricular, suprachiasmatic, paraventricular, arcuate,
      dorsomedial and supramammillary nuclei, the paraventricular thalamic nucleus, the
      ventral lateral geniculate nucleus (magnocellular part), the pontine nuclei, the
      dorsal and dorsolateral tegmental nuclei, the parabrachial nucleus (Kolliker-Fuse
      nucleus), the locus coeruleus, and the nucleus of the solitary tract. Among them,
      the paraventricular and suprachiasmatic hypothalamic nuclei exhibited the most
      dense concentration of c-Fos-IR cells and intensity. These results indicate that
      the c-Fos expression in the brain is induced by transsynaptic stimulation. The
      findings that there was a clear difference in the distribution of c-Fos-IR cells
      and in intensity between the experimental and control animals in the lumbosacral
      segment of the spinal cord but not in the upper portion and the brain, suggested
      that there is poor discrimination of nociceptive information in the brain between
      stimulation by nerve section and skin-incision.

PMID- 8270793
TI  - Astrocytes in the lamina cribrosa of the rat optic nerve: are their morphological
      peculiarities involved in an altered blood-brain barrier?
AB  - The lamina cribrosa of the mammalian optic nerve is thought to build a barrier
      for oligodendroglia progenitor cells migrating from the optic nerve towards the
      retina. One of the best-known properties of this region is that all optic axons
      are unmyelinated. Additionally, the blood-brain barrier appears to be interrupted
      by free access of blood-borne substances from leaky choroid vessels at the
      surface of the nerve. Several authors suggested the astrocytes to be responsible
      for these unusual features of this part of the central nervous system. Therefore,
      we decided to study the astrocytes morphologically by means of ultrathin section
      and freeze-fracture replica investigation. The main results are the followings:
      1. In 12, 23 and 40 days old rats, axonal spheroids with multiple dense bodies
      were observed within the lamina cribrosa, but not in the optic nerve proper.
      Large vacuoles with similar inclusions were found in cells of the lamina cribrosa
      of adult rats which were identified as astrocytes by the occurrence of gap
      junctions and intermediate filaments. We assume that lamina cribrosa astrocytes
      have phagocytozed degenerating axonal spheroids. Microglial cells appear to be
      not involved in this process. 2. Freeze-fracture replicas allow to study the
      distribution of orthogonal arrays of particles (OAPs) in astrocytic membranes.
      The OAP polarity index (ratio of OAP-densities or OAP-areas in endfoot versus non
      endfoot membranes) is reduced in the lamina cribrosa, as was shown previously by
      Rohlmann et al. (1992) in the myelin-deficient (md) rat mutant, too. We conclude
      that non-myelination reduces the polarity of astrocytes and discuss the
      possibility of an interrelationship between myelination, axonal growth,
      astrocytic properties and quality of the blood-brain barrier.

PMID- 8270794
TI  - [Studies on respiratory infection with Pasteurella multocida].
AB  - A questionnaire style survey on Pasteurella multocida infection was conducted at
      on 528 laboratories of hospitals. The questionnaire included the detection of
      Pasteurella multocida from sputum, the age distribution, underlying disease etc.
      of the patients. In Japan, infectious diseases caused by Pasteurella multocida
      were found in 179 cases in 67 (26.0%) of the 258 hospitals. The incidence of the
      infections tends to increase, 18 cases in 1989, 25 cases in 1990, 18 cases in
      1991 (Jan.-Jul.). These 179 cases were broken down into 44 males (from 1 year old
      to 85 years old, mean 58.9 years old), 45 females (from 18 years old to 85 years
      old, mean 60.2 years old), and 90 patients whose sex was unknown. Underlying
      diseases were recognized in 72 cases. Diseases related to the respiratory organ
      were 61 (84.7%) cases. The cases of hemo-sputum had to be differentiated from
      malignant tumors Recurrent Pasteuralla multocida infections were recognized in 4
      males and 4 females. And the 4 cases had been handling animals. There were only
      26 cases who had contact with animals, the others were unknown. This result
      suggested that contact with animals may cause these infections. Recently, the
      detection of Pasteurella multocida from the sputum tends to increase. The elderly
      patient with chronic pulmonary disease, who is handling animals must be educated
      on hygiene and zoonosis.

PMID- 8270796
TI  - [A study on the bactericidal activity of povidone-iodine in the synthetic
      mediums].
AB  - To evaluate the bactericidal activity of povidone-iodine (PVI), synthetic mediums
      without the protein components were prepared. The stability of the available
      iodine in the synthetic mediums was compared with that in heart infusion broth
      (HIB; natural broth). The available iodine was remarkably decreased soon after
      addition of PVI in the HIB, but it was stable for 24 hr in the synthetic mediums.
      The growth of Escherichia coli and Salmonella enteritidis were found to be normal
      in the synthetic mediums. Minimal inhibitory concentrations (MICs) of PVI in the
      synthetic mediums were about one thousandth of that in HIB, and the phenol
      coefficients (PCs) of PVI in the synthetic mediums were about 30 times lower than
      that in the HIB.

PMID- 8270795
TI  - [Differentiation of cholera-enterotoxin producing Vibrio strains by polymerase
      chain reaction].
AB  - The pathogenic factor of Vibrio cholerae that induces a severe watery diarrhea in
      humans is cholera enterotoxin (CT). We have earlier reported on the use of a
      specific polymerase chain reaction method (PCR) for confirmation of CT
      production. In our results, a few CT-producing V. mimicus strains were detected
      by the method. Here we report on the PCR method using 2-primer sets in the same
      tube for differentiation of toxigenic V. cholerae (O1 and non-O1) and toxigenic
      V. mimicus. One primer pair is for CT-gene (ctx), and the other pair is for the
      toxR gene which regulates the ctx gene of V. cholerae. ToxR genes were detected
      in all CT-producing V. cholerae (both O1 and non-O1). There were no isolates of
      the ctx gene positive and toxR gene negative in all V. cholerae strains. On the
      other hand, V. mimicus strain has not recognized toxR genes except one strain
      which is similar to the character of V. cholerae. These results indicates that
      the CT-producing V. cholerae strains are regulated by the toxR gene, but the ctx
      gene of V. mimicus is controlled by another different genome from toxR of V.
      cholerae.

PMID- 8270797
TI  - Internal bacterial flora of solid uterine cervical cancer.
AB  - Twenty-five patients with uterine cervical cancer (Two cases stage O; four cases
      stage Ia; five cases stage Ib; one case stage IIa; ten cases stage IIb; two cases
      stage IIIa; one case stage IVa) served as the subjects. The bacterial flora
      inside the cervical cancers was investigated using the optimal technique. There
      was mixed abnormal aerobic and anaerobic bacterial flora in all subjects. The
      average number of bacterial species isolated from inside the cervical cancers was
      6.3. The predominant bacteria isolated were the aerobes, Staphylococcus
      haemolyticus, Streptococcus agalactiae, Escherichia coli and Gardnerella
      vaginalis, and Prevotella bivia. As the stages of cervical cancer progressed, G.
      vaginalis, B. distasonis and P. bivia were detected at higher rates and higher
      counts than other bacteria. These findings suggest that there is a relationship
      between G. vaginalis, B. distasonis and P. bivia and the onset and growth of
      cervical cancer.

PMID- 8270798
TI  - [Study of Legionella pneumophila detection by two step polymerase chain
      reaction].
AB  - We studied the usefulness of two sets of primers in macrophage infectivity
      potentiator gene sequence of Legionella pneumophila. PCR by 1st step primers
      produced 649 bp DNA bands and 2nd step primers 489 bp DNA bands. Two step PCR by
      these primers produced 489 bp DNA bands specific for L. pneumophila. Two step PCR
      detected 10 fg of pure DNA extracted from L. pneumophila, Philadelphia-1 strain.
      PCR sensitivity by these primers was superior to former primers reported by us
      using intratracheal aspirates collected from the patient with L. pneumophila
      serogroup 2 pneumonia.

PMID- 8270799
TI  - [Epidemic of aseptic meningitis with echovirus type 30 in Gifu Prefecture].
AB  - During July to December in 1991, an epidemic of aseptic meningitis occurred in
      Gifu Prefecture in children. Epidemiological, virological and serological
      investigations were performed. The results are as follows: 1) Cases involved
      ranged from 0 to 13 years of age, and 75.9% of them were in the 3 to 7 year of
      age group. 2) Three types of enteroviruses were isolated from 83 of 133 cases
      (62.4%), and the echovirus type 30 was recovered from 71 cases (85.5%). 3) In
      1991 with the cross neutralizing test between the prototype and isolated strains
      of echovirus type 30, a remarkable antigenic variation could not be found. 4) In
      serological studies, the positive rates of neutralizing antibodies to echovirus
      type 30 in infant sera aged 0-9 years in 1992-1993, was 51.9% with the prototype
      strain, but 34.0% with an isolated strain in 1991.

PMID- 8270800
TI  - [Studies of neutrophil function in the elderly: especially analysis of bedridden
      patients and patients with bacterial infection].
AB  - To evaluate the host defense function in the elderly, chemotaxis and
      chemiluminescence (CL) were assessed as indicators of neutrophil function in
      healthy and bedridden subjects as well as in patients with bacterial infection.
      In addition, humoral host defensive factors were also investigated. 1) The
      differences in chemotaxis and CL between healthy elderly subjects and healthy
      adults were slight. Neutrophil function showed little decrease with aging. 2)
      Plasma fibronectin (PFN) values in bedridden patients were lower than in healthy
      elderly subjects. 3) Chemotaxis and CL in patients in the acute phase of
      bacterial infection were higher than those of healthy elderly subjects regardless
      of whether these patients were bedridden or not. CL was slightly lower in
      bedridden patients than in non-bedridden patients. CL and body temperature were
      positively correlated in the acute phase of bacterial infection. Among the
      humoral defensive factors, PFN revealed lowered values in the acute phase of
      bacterial infection. 4) As the infection healed, chemotaxis and CL decreased,
      while PFN rose to normal. In the complement system, CH50 increased slightly as
      the infection healed. From these results, we concluded that neutrophil function
      in elderly subjects, regardless of whether they were bedridden or not, is
      enhanced by infection. Responses to infection of bedridden patients were slightly
      weaker than those of non-bedridden subjects.

PMID- 8270801
TI  - [Superoxide generation by neutrophils as defence mechanisms in elderly].
AB  - We investigated superoxide generation by polymorphonuclear leukocytes (PMNs)
      stimulated with various species of bacteria in order to clarify the species
      specific immunocompromised status in the elderly. We studied 66 elderly patients
      (ranged 66 to 89 year-old; mean 77-year-old) and 26 young healthy volunteers
      (ranged 25 to 3-year-old; mean 31-year-old) as a control group. The elderly
      patients were divided into two groups, i.e., the malignancy group and the benign
      group. Peripheral blood was prepared from each host and diluted. The activity of
      superoxide generation by PMNs was determined by means of chemiluminescence
      method. PMNs were stimulated with the standard stimulants; i.e., phorbol
      myristate acetate (PMA) and zymosan (ZY), and four bacterial species; i.e.,
      Escherichia coli, Psudomona aeruginosa, Staphylococcus aureus and Candida
      albicans. The activity of superoxide generation by PMNs in the malignancy group
      was significantly lower than that in the control group (p < 0.05). Furthermore,
      the activity of superoxide generation by PMNs in the malignancy group and the
      benign group stimulated with C. albicans were significantly lower than those in
      the control group (p < 0.05). These results indicate that the elderly are in an
      immunocompromised status especially against fungus such as C. albicans.

PMID- 8270802
TI  - [Inhibitory effect of mouse antiendotoxin monoclonal antibody (E5) on hypotension
      induced by endotoxin and TNF-alpha].
AB  - Mouse anti-endotoxin monoclonal antibody (E5) is now under clinical trial (Phase
      II) in Japan by assessing clinical findings and plasma endotoxin levels. We
      attempted to evaluate an inhibitory effect of E5 on hypotension induced by
      endotoxin and TNF-alpha. Systolic blood pressure was measured with a programmable
      sphygmomanometer using the tail-cuff method. The mixture of endotoxin (E. coli
      O111:B4, Sigma, 2 micrograms/mouse) and recombinant mouse TNF-alpha (Genzyme,
      8000 units) were injected into mice (ddY, 6-8-weeks-olds), and the change of
      blood pressure was observed for 3 hrs. The mixture significantly decreased the
      blood pressure to about 70% of the control. E5 (20 micrograms/mouse), which was
      injected 10 min before, significantly abrogated the effect of endotoxin and TNF
      alpha. The hypotension induced by the mixture was definitely inhibited by the
      injection of E5 (50, 100 micrograms/mouse), injected 10 min later, or the
      injection of E5 (100 micrograms/mouse) 30 min later. We previously found that E5
      prevents the lethality induced by a concomitant injection of endotoxin, TNF-alpha
      and IL-2. These results suggest that E5 effective for inhibition of endotoxin
      activity in vivo.

PMID- 8270803
TI  - [A case of cytomegalovirus pneumonia and Pneumocystis carinii pneumonia with lung
      cancer--diagnosis by the polymerase chain reaction].
AB  - A 64-year-old male was admitted to Oita Medical University Hospital because of
      primary lung cancer. After the anticancer chemotherapy, the patient developed a
      high fever. His chest X-ray showed diffuse reticular shadows bilaterally, which
      were considered to be a drug induced pneumonia, then pulse therapy with
      corticosteroid was performed. With this treatment, the diffuse reticular shadows
      disappeared. One month later, however, a severe interstitial pneumonia developed,
      and the patient died of respiratory failure. Autopsy findings demonstrated
      cytomegalovirus (CMV) and Pneumocystis carinni pneumonia. The polymerase chain
      reaction (PCR) for CMV in mononuclear cells in the blood was positive through out
      his hospitalization. In the sera, however, it was negative at the time of
      admission, then became positive 10 days before the onset of pneumonia. In
      addition, the PCR for P. carinni on the swab became positive as well. These
      results imply that PCR can be used for diagnosis of CMV and P. carinii infections
      from sera or swabs.

PMID- 8270804
TI  - [A case report of miliary tuberculosis with tubercular meningitis diagnosed and
      followed by polymerase chain reaction method].
AB  - We report here a case of miliary tuberculosis with tubercular meningitis in which
      the polymerase chain reaction (PCR) amplification method was useful for its rapid
      diagnosis and follow up. A 70 year old male was hospitalized for further
      examination and treatment of diffuse small nodular shadows on the chest X-ray.
      After receiving antimicrobial therapy shadows still remained and he gradually
      lost visual acuity. He had no meningeal signs, and no remarkable finding on
      cranial CT. Cerebrospinal fluid examination showed increased cell number with
      predominantly lymphocytes. Cranial MRI (Gd DTPA) showed lateral ventricular
      ependymitis. Pulmonary tuberculosis and secondary tubercular meningitis were
      suspected, but we failed to detect microorganisms from the cerebrospinal fluid,
      gastric juice, sputum, and urine by the conventional method. However, by the
      polymerase chain reaction amplification method specific DNA fragments of
      Mycobacterium tuberculosis complex was detected from the cerebrospinal fluid,
      gastric juice, bronchoalveolar lavage fluid and serum. The final diagnosis of
      miliary tuberculosis with tubercular meningitis was established. We administered
      antitubercular drugs and observed the clinical course. He recovered and the
      polymerase chain reaction showed negative consequences in all samples. The
      judgement of PCR and the clinical course were compatible and parallel with the
      clinical course.

PMID- 8270805
TI  - Low opsonic activity in sera from HIV-infected patients against Streptococcus
      pneumoniae.

PMID- 8270806
TI  - [Susceptibility to arbekacin in Pseudomonas aeruginosa isolated from clinical
      specimens].

PMID- 8270807
TI  - [A study of HCV infection in patients with chronic hemodialysis without blood
      transfusion].

PMID- 8270808
TI  - Epilepsy in the elderly.
AB  - Other than children under the age of 5 years, the highest incidence of new onset
      epilepsy occurs in the population over 65 years of age. Risk factors in this age
      group include stroke, head trauma, dementia, infection, alcoholism and aging.
      Clinically, seizure behavior may be confused with other neurological impairments,
      thus delaying accurate diagnosis. Concomitant drug therapy affects the choice of
      antiepileptic drugs. Neuroscience nurses need to identify high-risk patients,
      recognize and document seizure activity and adverse drug reactions and
      interactions, and modify traditional seizure first aid for the frail elderly. An
      understanding of the psychosocial impact of epilepsy is necessary when offering
      education and support to the patient and family.

PMID- 8270809
TI  - Ventilator-assisted youth: appraisal and nursing care.
AB  - An interdisciplinary review of 16 ventilator-assisted, cervical-cord injured
      youth, aged 3-19 years, was completed to explore long-term outcomes and develop
      recommendations for care. Ten youths were younger than 12 years; 6 were
      adolescents. The mean initial hospital length of stay was 192 days. Discharged
      youths were followed for 1-73 months after hospitalization. Nursing implications
      were developed using a systems approach with North American Nursing Diagnosis
      Association (NANDA) approved diagnoses. Nursing case management was used to
      coordinate discharge planning and continuity of care. At the time of data
      collection 13 youths had been successfully reintegrated to home, school and
      community, the least restrictive environments for all.

PMID- 8270810
TI  - Gaucher's disease: a pilot study of the symptomatic responses to enzyme
      replacement therapy.
AB  - Symptomatic responses to enzyme replacement therapy were studied in 12 patients
      with an inherited lipid storage disorder (Type 1 Gaucher's disease) in order to
      determine the impact of treatment on perceptions of well being. Before each
      intravenous infusion of enzyme, patients were asked to comment on the presence or
      absence of disease-specific symptoms presented in questionnaire format. Symptoms
      were grouped into five major categories: bleeding abnormalities, chronic fatigue,
      gastrointestinal complaints, bone pain and psychosocial function. Each reported
      symptom was discussed in detail with the clinic nurse coordinator and documented
      in the medical record. After six months of enzyme replacement therapy, each
      patient's chart was reviewed and changes in the frequency of disease-specific
      symptoms over time were evaluated. The major subjective changes included a
      decrease in the frequency and severity of nosebleeds, reduced bruising, increased
      vigor and energy level, visible reduction in abdominal girth, increased self
      esteem and enhanced self-image. Patients frequently described relief of their
      symptoms well before changes were confirmed by objective laboratory measurements.
      These observations may prove useful in the comprehensive management of patients
      with Gaucher's disease as they recover from a chronic, debilitating illness while
      receiving enzyme replacement therapy. The extent and ease with which these
      patients can achieve a state of normal, healthy function is unknown at the
      present time and will require further study.

PMID- 8270811
TI  - The relationship of selected nursing activities to ICP.
AB  - Study of a number of routine nursing care activities has suggested a relationship
      between activities and intracranial pressure (ICP). The purpose of this study was
      to focus on the relationship between nursing care activities and variations in
      ICP. A case study method was used to study ICP in five brain-injured patients
      with a Glasgow Coma Scale (GCS) score of 4 or more. Each patient's condition
      warranted continuous ICP monitoring with a fiberoptic catheter in a neurological
      intensive care unit (ICU) of two hospitals in the Upper Midwest. Selected nursing
      measures--turning, suctioning and bathing--were recorded on the data collection
      tool as they occurred. Suctioning and turning were noted to be associated with an
      increase in ICP; however, a sustained increase in ICP was not observed. During
      the bathing procedures only two baths elicited an ICP greater than 20 mm Hg. All
      other bathing procedures elicited minimal increases in ICP. These findings
      further support the need for nurses to be aware of the patient's ICP prior to
      turning and suctioning.

PMID- 8270812
TI  - Noninvasive bladder volume measurement.
AB  - The aim of this study was to compare the accuracy of bladder volume measurements
      using a portable ultrasound machine to measurement by catheterization. For 13
      consecutive weeks, all patients admitted to the stroke unit at Royal Perth
      Hospital were studied by both methods when urinary retention was suspected. The
      accuracy of ultrasound bladder volume measurements and interobserver reliability
      were evaluated. Ninety ultrasound examinations were performed prior to
      catheterization, 70 were by one nurse, and 20 independently by two nurses.
      Correlation of ultrasound measurements with actual catheterized volume was highly
      significant (r = 0.983) as was interobserver reliability. The study showed that
      noninvasive bladder volume measurements using ultrasound are safe, effective,
      inexpensive and a useful adjunct to preventive bladder management and continence
      management in stroke patients.

PMID- 8270813
TI  - Continuous duodenal infusions of levodopa.
AB  - Infusion of carbidopa/levodopa or levodopa through a duodenal tube can facilitate
      increased mobility and functional ability in individuals with Parkinson's disease
      when conventional drug therapy is unsuccessful in achieving desired outcomes.
      Therapy requires appropriate patient selection, ongoing assessment of the
      patient's physical and emotional needs and collaboration between the patient,
      nurses and physicians. Determining the amount of medication required to achieve
      the desired outcomes takes time. Implantable pumps may be a future strategy.
      Future research should focus on patient and family coping throughout
      hospitalization and at home so the emotional needs of this specific population
      can be met.

PMID- 8270814
TI  - Scientific integrity in nursing research.
AB  - Though scientific knowledge is presumed to be true, misconduct in generation and
      reporting of research has occurred. Causes of scientific misconduct may be
      personal, such as excessive ambition, or organizational, such as withholding
      negative results about a product for economic gain. Ethical conduct of science
      involves respect for persons, beneficence and justice throughout the research
      process. The bottom line is researchers must have the integrity to be truthful
      themselves and the courage to report disreputable practices. Nurses must conduct
      scientific endeavors and practice the science of nursing with integrity.
      Maintaining integrity is essential for the advancement of nursing as a science,
      and therefore, ongoing improvement in nursing care.

PMID- 8270815
TI  - The ethics of role conflict in research.
AB  - While engaged in interviewing stroke patients, nurses found their research
      responsibilities conflicting with traditional patient care values. At the
      termination of the pilot project, the nurses, doubting their role, shared their
      concerns with the research team. They made recommendations regarding the
      appropriateness of tools and training needs of research assistants. Unresolved
      role conflict motivated the nurses to review the literature, seeking answers to
      the issue. Other nurses have experienced this same conflict. While nursing has
      been referred to as a profession that complements art with science, in practice,
      altruism may conflict with maintaining research integrity. The nurse, when
      functioning as a researcher, may find situations where a choice needs to be made
      whether to implement nursing interventions or continue the research protocol. The
      difficulty remains in deciding when the patient advocate role takes precedence
      over other legitimate concerns. Even though the ANA Code for Nurses with
      Interpretive Statements requires that the nurse participate in research to
      advance the profession's body of knowledge, the code's primary principle mandates
      respect for the rights of the individuals the nurse serves. Research need not be
      undertaken at the expense of human dignity. If conflicts develop, nursing's
      primary responsibility is to the individual. Concern for the individual always
      takes precedence over maintaining research integrity. Nurses are "advocates,
      where trust, compassion, and empathy encompass all our nursing endeavors,
      including research" (p. 161). While striving to achieve research goals, nurses
      must not lose sight of the traditional values inherent in nursing.

PMID- 8270816
TI  - [Molecular neurobiology of Alzheimer amyloid protein precursor].

PMID- 8270817
TI  - [Hemoglobin M disease].

PMID- 8270818
TI  - [Tissue-specific calpain and ubiquitous calpain].

PMID- 8270819
TI  - [Structure and function of bacterial flagella].

PMID- 8270820
TI  - [Changes of estrogen receptor contents in the uterine myometrium of rats during
      gestation].
AB  - It is well known that estrogen plays an important role in the uterine contraction
      during labor, and should be mediated through estrogen receptor (ER) in the
      uterine muscle. This study shows the changes in the amount of ER in the
      myometrium during pregnancy and labor in rats. The uterus was dissected from
      pregnant rats (SD strain) on days 9, 12, 15, and 21 of pregnancy, and during
      labor. The uterine tissues were divided into those from the site (placental site)
      and those from opposite the site (non-placental site), of the placental
      attachment. ER concentrations were determined with ER-EIA kits (Abbot Co.). ER
      content in the non-placental site was almost the same at diestrus 1, and days 9,
      12, 15, of pregnancy and also during labor, except on day 21 when ER content was
      significantly (p < 0.05) lower than on any other day tested. ER content in the
      placental site was significantly (p < 0.01) higher on day 9 than in the non
      pregnant status (diestrus 1), but decreased thereafter until day 21, showing
      significantly (p < 0.01) lower values on day 21 than on day 12 or diestrus 1. The
      decrease in ER values on day 21 was eliminated by removing all fetuses, but not
      the placentas, on day 12. During labor, ER content in the non-placental site was
      increased significantly (p < 0.01), but in the placental site it did not increase
      significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270821
TI  - [Flow cytometric evaluation of DNA ploidy pattern and cell heterogeneity in
      cervical dysplasia and carcinoma in situ].
AB  - Using flow cytometry DNA ploidy was evaluated in 77 cases with cervical dysplasia
      and 35 cases with squamous cell carcinoma in situ (CIS, small cell type or
      intermediate cell type) to investigate changes that may characterize the genomic
      process leading to the development of cervical squamous cell carcinoma. The co
      efficient of variation (CV) in the DNA histogram for fresh human leucocytes
      ranged from 0.7% to 1.2%, and that for dysplasia or CIS was 3.6% on the average.
      DNA aneuploidy was observed in 77.8%, 93.3%, 100%, and 97.1% of the cases with
      mild dysplasia (n = 9), moderate dysplasia (n = 3), severe dysplasia (n = 47),
      and CIS (n = 35), respectively. Heterogeneity (No. of aneuploid populations > or
      = 2) was seen in 11.1%, 23.3%, 76.6%, and 28.6% of the cases in each histological
      type, respectively. While aneuploid populations with a DNA index above 1.5 (and
      around 2.0) were frequently observed in the cases with severe dysplasia, these
      were not frequently observed in the cases with squamous cell CIS. It is suggested
      that the heterogeneity observed in severe dysplasia is an expression of enhanced
      genomic instability which leads to evolution of multiple tetraploidized
      populations in this precursor.

PMID- 8270822
TI  - [Avidity of rubella IgG antibody in rubella virus infection].
AB  - The avidity assay of rubella IgG antibody with urea was evaluated to distinguish
      the early convalescent phase of primary rubella from the late one and
      reinfection. We examined 116 sera from 23 patients with primary infection
      collected 7 to 1,477 days after the rash appeared and 25 sera from 8 patients
      with rubella reinfection and 16 sera from 15 pregnant women without fetal
      infection having high hemagglutination inhibition (HI) antibody or weak positive
      rubella IgM antibody. The avidity index (AI) was calculated as the ratio of the
      optical density from the urea-washed well to that of the non-treated well,
      expressed as a percentage. In primary infection AI were lower than 30% within 30
      days after the rash appeared, then gradually increased and reached a plateau of
      60 to 80% three months later, whereas the AIs of patients after reinfection, with
      high HI antibody and weak positive IgM antibody were as high as 79.2 +/- 7.5%,
      93.5 +/- 4.1% and 90.6 +/- 5.0%, respectively. These results indicate that the
      measurement of avidity in rubella IgG antibody is valuable in diagnosing recent
      primary rubella in pregnant women having a high HI antibody or IgM antibody.

PMID- 8270823
TI  - [Power spectral analysis of spontaneous rhythm in peripheral blood flow in fetal
      lamb].
AB  - Fluctuations in fetal hemodynamic parameters are commonly observed, and we can
      use the variation in the fetal heart rate as an index in fetal assessment. The
      purpose of this study was to clarify the spontaneous rhythm in systemic
      circulation in fetal lambs by means of power spectral analysis. Three pregnant
      sheep and their fetuses at 125 and 135 days of gestation were surgically
      instrumented and studied. After a minimum recovery period of four days, a fetal
      electrocardiogram was taken and arterial blood pressure was recorded. They were
      also examined in the absence of heart rate variation by means of fetal cardiac
      pacing. We used an autoregressive model to estimate their power spectral
      densities. In normal fetal lambs, two spontaneous rhythms were detected in the
      spectra for the fetal heart rate and arterial blood pressure. Spectral analysis
      of arterial blood pressure variation in the absence of heart rate variation
      revealed that there was only one consistent major spectral component around 0.15
      Hz. This suggests that fluctuations are caused not by a variation in the heart
      rate but by a variation in peripheral motor activity. This spontaneous rhythm in
      peripheral resistance may be associated with the sinusoidal heart rate pattern in
      the fetal cardiotochogram.

PMID- 8270824
TI  - [Determination of intrauterine pressure using catheter-tip transducer inserted
      outside fetal membranes].
AB  - To determining intrauterine pressure outside fetal membranes, we used a catheter
      tip transducer to study 20 women before the occurrence membrane rupture. Their
      mean age was 28.2 +/- 3.4 years and all women were in weeks 37 to 41 of pregnancy
      when studied. In the first stage of labor, the peak intrauterine pressure was
      60.0 +/- 12.5 mmHg (mean +/- SD) when the external os was dilated 4 to 6 cm, 90.0
      +/- 14.8 mmHg, at 7 to 8 cm dilation, and 80.0 +/- 11.5 mmHg at 9 cm or greater
      dilation. Each pressure wave lasted 45 to 55 sec. The highest baseline pressure
      (28.0 +/- 4.5 mmHg) was obtained when the subjects were sitting. A baseline
      pressure of 17.0 +/- 4.0 mmHg was obtained in the supine position, as well as a
      value of 21.0 +/- 3.5 mmHg in the recumbent position. There were no complications
      related to the catheter-tip transducer. Our findings indicate that this method is
      both accurate and reliable in determining the amounts of intrauterine pressure to
      which fetal membranes are subjected.

PMID- 8270825
TI  - [Urodynamic investigation in the management of incontinent women with genital
      prolapse].

PMID- 8270826
TI  - [A new culture model of human tubal epithelial cells on Matrigel].

PMID- 8270827
TI  - [A case of eclampsia with cerebral vasospasm demonstrated by MR angiography
      without evidence of cerebral ischemia by CT and MRI].

PMID- 8270828
TI  - [A case of premature ovarian failure accompanied by memory disorder after the
      discontinuation of estrogen replacement therapy].

PMID- 8270829
TI  - [Two cases of hypovolemic shock by massive bleeding associated with submucous
      leiomyoma during buserelin treatment].

PMID- 8270830
TI  - [A trial of isolation in chemotherapy for gynecological malignant tumor by MTT
      assay].

PMID- 8270831
TI  - [A case of invasive mole with Basedow's disease].

PMID- 8270832
TI  - [Computed tomogram and magnetic resonance imaging of a case suffering from
      blindness in postpartum eclampsia].

PMID- 8270833
TI  - [A case of huge abdominal unilocular peritoneal inclusion cyst].

PMID- 8270834
TI  - Automated evoked potential monitoring.
AB  - We have developed a computer system for use in the operating room and intensive
      care unit for the automated acquisition and classification of flash evoked
      potentials. The project goals were to: (1) acquire evoked potentials without user
      intervention; (2) recognize, label, and trend important parameters; and (3) alarm
      if parameters deviate too far from normal. The system consists of a Nicolet
      Pathfinder, programmed for periodic flash visual evoked potential acquisition and
      a personal computer for analysis. Analysis software utilizes the C+ +language.
      The system has been tested on sixteen cases, determinations of specific waveforms
      were validated ex post facto by two experts. Three parameters in each of three
      channels were correctly recognized in more than 87% of all waveforms acquired. No
      signals at all were obtained in only 0.8% of all samples.

PMID- 8270835
TI  - The Arden syntax for medical logic modules.
AB  - The Arden Syntax for sharing medical knowledge bases is described. Its current
      focus is on knowledge that is represented as a set of independent modules that
      can provide therapeutic suggestions, alerts, diagnosis scores, etc. The syntax is
      based largely upon HELP and the Regenstrief Medical Record System. Each module,
      called a Medical Logic Module or MLM, is made of slots grouped into maintenance,
      library, and knowledge categories. The syntax has provisions for querying a
      clinical database and representing time. Several clinical information systems
      were analyzed and appear to be compatible with the syntax. The syntax has been
      tested for syntactic ambiguities using the tools lex and yacc. Seventeen
      institutions are currently in the process of adopting the Arden Syntax for their
      decision-support systems. A subcommittee of ASTM has been formed to develop
      standards for sharing medical knowledge bases. The Arden Syntax has been
      published by ASTM as a initial standard for sharing medical knowledge.

PMID- 8270836
TI  - An object-oriented approach to data display and storage: 3 years experience,
      25,000 cases.
AB  - Object-oriented programming techniques were used to develop computer based data
      display and storage systems. These have been operating in the 8 anaesthetising
      areas of the Adelaide Children's Hospital for 3 years. The analogue and serial
      outputs from an array of patient monitors are connected to IBM compatible PC-XT
      computers. The information is displayed on a colour screen as wave-form and trend
      graphs and digital format in 'real time'. The trend data is printed
      simultaneously on a dot matrix printer. This data is also stored for 24 hours on
      'hard' disk. The major benefit has been the provision of a single visual focus
      for all monitored variables. The automatic logging of data has been invaluable in
      the analysis of critical incidents. The systems were made possible by recent,
      rapid improvements in computer hardware and software. This paper traces the
      development of the program and demonstrates the advantages of object-oriented
      programming techniques.

PMID- 8270837
TI  - A clinical computer database entry form for an intraoperative anesthesiology
      based transesophageal echocardiography monitoring service.
AB  - Transesophageal echocardiography (TEE) has been increasingly applied to
      supplement and, in instances, to supplant conventional intraoperative cardiac
      monitoring. Our body of experience (> 1600 intraoperative TEE procedures),
      combined with insights gleaned from an intramural quality assurance study, and
      clinical implications of certain recent advances in the field, led us to develop
      the following TEE computer database entry form. The form, completed
      intraoperatively, consists of a patient and surgical procedure demographics
      section, followed by fields based on the TEE examination. The scans encompass
      transverse plane basal short axis, long axis, and transgastric views of the heart
      and great vessels. The two-dimensional echocardiographic, saline-contrast, color
      flow and pulsed Doppler data represent both right and left ventricular
      performance, valvular function and specific lesions. This database entry form is
      intended to serve as a guide for performance of a nominally complete
      intraoperative study and facilitate maintenance of a TEE archive consistent with
      current advances.

PMID- 8270838
TI  - Object-oriented data management: an approach to computerized anaesthesia
      documentation.
AB  - The main problem of today's anaesthesia department is that it spans a
      multiplicity of locations for data management dealing with data on the pre-OP,
      intra-OP, and post-OP situation as well as with data obtained from the
      laboratories, the administration, etc. In the operating room itself, numerous
      monitoring devices and anaesthesia machines have to be integrated into the
      anaesthesia documentation process. Therefore, computerized anaesthesia
      documentation as a part of quality control urgently needs sufficient support for
      handling both medical and administrative data, taking into account that the user
      usually is not a computer expert. We will describe an approach to solve the
      problem discussed applying object-oriented technology in medical data management,
      and a sequence of technical realization steps to bring this technology into
      clinical use.

PMID- 8270839
TI  - Ergonomics applied to anaesthesia record keeping.
AB  - For almost 100 years, the anaesthesia record has been the sole information tool
      trying to fulfill an ample catalogue of functions related to the anaesthesia
      information processes. Automated anaesthetic record systems have evolved around
      data being available online, as an imitation of the handwritten record. None has
      developed an information tool capable of an efficient utilization of the wide
      range of resources provided by modern technology to fulfill the information
      requirements of the anaesthetic environment. We used a system ergonomic analysis
      trying to find the best solutions. As a result of it we drafted an Anaesthesia
      Information Concept (AIC) in which the complexity of data & information (D&I)
      processes is broken down to modules called Clinical Information Process Units
      (CIPUs). A CIPU is mainly defined by the responsibility of a staff member and
      focuses on the basic system patient, staff and machine (all devices). The
      internal functions of a CIPU are treatment control and medicolegal documentation.
      The external functions are fulfilled by transferring required sets of D&I for
      subsequent treatment control (next CIPU), audit, quality control, cost
      calculation, etc. Using such an approach, an Anaesthesia Information Concept
      (AIC) can be realized by a wide range of modular and hybrid systems (combination
      of different tools such as paper records, computers, etc), as opposed to
      universal and single automated documentation systems, which up to now have failed
      to fulfill the information demands of the anaesthetic environment.

PMID- 8270840
TI  - ECG of the month. Final solution. Ventricular ectopy.

PMID- 8270841
TI  - Thyroglossal duct cysts.
AB  - The thyroglossal duct cyst (TGDC) is the most common congenital neck mass and the
      second most common of all childhood cervical masses. An anterior midline neck
      mass presenting before the age of twenty and displaying vertical movement with
      tongue protrusion and swallowing is characteristic of this lesion. Though
      concomitant agenesis of the thyroid is extremely rare, documentation of a normal
      thyroid preoperatively has become a legally protective requirement. Carcinoma in
      a TGDC is unusual and is rarely detected preoperatively, but a fine needle
      aspiration is helpful if a malignancy is suspected. Regardless, the treatment is
      a Sistrunk procedure: excision of the cyst, the tract connecting it to the
      foramen cecum, and the central portion of the hyoid bone.

PMID- 8270842
TI  - Louisiana's need for primary care physicians: let's not forget the role of
      medical education.
AB  - Louisiana's need for primary care physicians remains among the highest in the
      nation. The state's rural nature, the aging of current family and general
      practitioners, the low output of new family physicians, and an increased demand
      for generalists as a result of changes in health care delivery has exacerbated
      the situation. Despite the need, the state's medical schools have lagged in terms
      of the entry of its graduating medical students into primary care, especially
      family medicine. The tertiary nature of the medical school setting and lack of
      generalist role models on the faculty have contributed to the declining interest
      in primary care. Several encouraging changes are underway in medical education in
      Louisiana that may support the production of more generalists, although the
      pipeline is long.

PMID- 8270843
TI  - The health care industry re-looks at the issue of health care provider ownership
      in entities to which they refer patients: Stark law II is upon us.

PMID- 8270844
TI  - The athlete and HIV.
AB  - Physicians are called upon to provide information and guidance concerning HIV and
      AIDS. Education and prevention are important elements in halting this dreaded
      disease. Athletes are at risk for exposure to HIV because of close contact and
      the potential for bleeding and resulting exposure. The risk of actual
      transmission is more potential than real. Precautions should always be taken so
      that athletes and those caring for them can minimize risks of exposure and
      transmission. To date, no conclusive case of HIV transmission has been reported
      in the athletic arena. Although this is reassuring, universal precautions should
      always be employed.

PMID- 8270845
TI  - Elevated lipoprotein (a) blood levels as the single treatable atherosclerotic
      risk factor in patients with coronary artery disease.
AB  - An elevated blood level of lipoprotein (a) [Lp(a)] has been studied as an
      independent risk factor for coronary artery disease. We report a series of nine
      consecutive patients with clinical onset or recurrence of coronary artery disease
      who presented without treatable atherosclerosis risk factors, five of whom had
      elevated Lp (a) blood levels. Indications for measuring Lp (a) levels and
      usefulness of niacin therapy are reviewed.

PMID- 8270846
TI  - False pregnancy: an unusual paraneoplastic syndrome associated with bronchogenic
      neoplasm.
AB  - Human chorionic gonadotropin (HCG) is typically associated with pregnancy or germ
      cell tumors. Although it may be detected within the tissue of a variety of
      malignant tumors by immunohistochemical methods, including primary lung cancers,
      serum levels are rarely elevated in non-germ cell malignancies. We describe a
      young lady who presented with chest discomfort and dyspnea. Clinically, she was
      thought to have deep venous thrombosis. She presumed that she was pregnant since
      her last menses was 3 months before admission. She also had breast tenderness
      similar to that which she had experienced during a previous pregnancy. A serum
      value for B-HCG suggested that she was 4 to 6 weeks pregnant. Further
      investigation confirmed that this patient was not pregnant, but had developed a
      gonadotropin secreting adenocarcinoma of the lung.

PMID- 8270847
TI  - Correlation between clinical, physical and laboratory features in children with
      EBV illness.

PMID- 8270848
TI  - History repeats itself or we have come full circle.

PMID- 8270850
TI  - Sun exposure.

PMID- 8270849
TI  - Management of prescribing.

PMID- 8270851
TI  - Transepithelial movement of calcium in crustaceans.
AB  - The regulation of calcium in most crustaceans is especially challenging owing to
      the highly mineralized cuticle that must be recalcified after each moult, a
      process that often occurs in environments with low concentrations of calcium. The
      gill and carapace epithelia separate the major calcium-containing compartments of
      the body and therefore see large changes in the rate of calcium flux through the
      moult cycle. Large changes in the ultrastructure of these cells do not, however,
      correlate well with the periods of calcium movement and probably reflect other
      physiological events. Despite the challenges to regulating calcium levels at
      various acclimation salinities and moult stages, the calcium concentration in the
      blood is maintained relatively constant. There is a rapid increase to a high rate
      of calcium flux across both the gill and carapace epithelium shortly after the
      moult; on an area-specific basis these fluxes are among the highest reported for
      calcium-transporting epithelia. When in water with a very low concentration of
      calcium, the electrochemical gradient for calcium is directed outwards and net
      influx must occur by active transport. Evidence suggests that changes in the
      electrochemical gradient, permeability and active transport are all important in
      the ability of crustaceans to take up calcium from water with a low concentration
      of this ion. Although an enzyme transporter is presumably involved in the active
      transport of calcium across epithelia, very little is known about the cellular
      mechanism of the transepithelial movement of calcium in crustaceans.

PMID- 8270852
TI  - Spatial aspects of Ca2+ signalling in pancreatic acinar cells.
AB  - Secretory cells do not only respond to an agonist with a simple rise in [Ca2+]i.
      It is now clear that complex patterns of [Ca2+]i elevation in terms of space and
      time are observed in many cell types and that these patterns may be a cellular
      mechanism for the regulation of different responses. Ca2+ signalling in exocrine
      cells of the pancreas promotes the secretion of digestive enzymes and fluid. It
      has been shown that at high concentrations of agonist (acetylcholine or
      cholecystokinin) the [Ca2+]i response is initiated in the secretory pole of the
      cell before spreading across the whole cell. This site of initiation of the
      [Ca2+]i elevation is in the region where exocytotic release of enzymes occurs and
      is also the site of a Ca(2+)-dependent chloride channel thought to be crucially
      important for fluid secretion. Lower concentrations of agonist elicit [Ca2+]i
      oscillations with complex repetitive patterns characteristic of each agonist. At
      physiological agonist concentrations, we have recently described repetitive short
      lasting Ca2+ spikes that are spatially restricted to the secretory pole of the
      cell. In addition to these spikes, cholecystokinin also promotes slow transient
      Ca2+ rises that result in a global rise in Ca2+. The inositol trisphosphate
      (InsP3) receptor plays a crucial role in all of these various agonist responses,
      most of which can be reproduced by the infusion of InsP3 into the cell. The high
      InsP3-sensitivity of the secretory pole is postulated to be due to a localization
      of high-affinity InsP3 receptors. We speculate that in response to
      cholecystokinin the short-lasting spikes elicit exocytosis from a small
      'available pool' of vesicles and that the broader oscillations induce both
      exocytosis and cell changes that involve movement of vesicles into this
      'available pool'.

PMID- 8270853
TI  - Modulation of signalling initiated by phosphoinositidase-C-linked receptors.
AB  - An extensive group of cell surface receptors are coupled to phosphoinositidase C
      and thus to the production of the intracellular second messengers inositol 1,4,5
      trisphosphate and 1,2-diacylglycerol. While the mechanisms and consequences of
      phosphoinositidase C activation have been the target of intensive study for over
      a decade, information is scarce regarding the regulatory processes that modulate
      this system during receptor stimulation. This situation, however, is now
      beginning to change. Recent data indicate (a) that Ca2+, mobilized concurrently
      with activation of phosphoinositidase-C-linked receptors, is a feedback activator
      and amplifier of phosphoinositide hydrolysis, (b) that rapid desensitization,
      possibly associated with receptor phosphorylation, regulates phosphoinositidase-C
      linked receptors, (c) that receptor internalization can mediate desensitization
      at later times and (d) that signalling can be regulated at additional sites
      downstream of phosphoinositidase C. These diverse regulatory events provide the
      means by which the breakdown of phosphoinositides and cellular responsiveness to
      their products are controlled during cell stimulation.

PMID- 8270854
TI  - Regulation of inositol 1,4,5-trisphosphate receptors.
AB  - Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] is a soluble second messenger
      responsible for the generation of highly organized Ca2+ signals in a variety of
      cell types. These Ca2+ signals control many cellular responses, including cell
      growth, fertilization, smooth muscle contraction and secretion. Ins(1,4,5)P3 is
      produced at the plasma membrane following receptor activation, but rapidly
      diffuses into the cytosol, where it binds to specific receptors through which it
      mobilizes intracellular Ca2+ stores. The actions of Ins(1,4,5)P3 within cells are
      tightly controlled: enzymes control the rapid generation and metabolism of
      Ins(1,4,5)P3 following receptor activation; multiple Ins(1,4,5)P3 receptor
      subtypes and splice variants exist, some of which are differentially expressed
      between cell types and at different stages of development; and Ins(1,4,5)P3
      receptors are the targets for a number of allosteric regulators, including
      protein kinases, ATP and divalent cations. Understanding how cells control the
      Ca(2+)-mobilizing activity of Ins(1,4,5)P3 will be important if we are to unravel
      the mechanisms that underlie the complex arrangements of Ca2+ signals.

PMID- 8270855
TI  - Stimulus-secretion coupling in excitable cells: a central role for calcium.
AB  - Secretion of vesicular contents by exocytosis is a common feature of
      neuroendocrine secretory cells such as adrenal chromaffin cells and PC12 cells.
      Although it is clear that in these cells an elevation in intracellular calcium
      concentration, [Ca2+]i, is the triggering event that induces secretion, recent
      studies using video-imaging, patch-clamp and flash photolysis techniques have all
      indicated that the Ca2+ signal that triggers secretion is in fact very complex,
      with the subcellular distribution of Ca2+ being of particular importance along
      with the magnitude of the rise. It has become evident that Ca2+ signals with
      different spatial profiles can be triggered in the same cell by a given stimulus,
      depending upon the nature of the Ca2+ signalling pathway activated, and that this
      ability to be able to vary the method of delivery of Ca2+ into the cell is
      important physiologically, because it provides a means of obtaining differential
      activation of Ca(2+)-dependent processes.

PMID- 8270856
TI  - Amphibian calcium metabolism.
AB  - Calcium is present in amphibian blood at a concentration similar to that in other
      vertebrates, about 1-2 mmol l-1. The fraction of free calcium in amphibians is
      lower than that in other tetrapod vertebrates because about 50% of the plasma
      Ca2+ is bound to plasma proteins and perhaps other molecules. Plasma [Ca2+]
      varies seasonally, increasing in spring and summer and decreasing in winter.
      Changes in plasma [Ca2+] also occur during larval development, as the
      concentration of this ion increases in larval forms as they approach
      metamorphosis. Calcium is exchanged at a variety of sites in animals. There is
      evidence for Ca2+ uptake across the skin and gills of larval anurans. It is also
      transported into the blood from the small intestine (especially the duodenum) and
      reabsorbed in renal tubules from the glomerular filtrate. The possibility of Ca2+
      absorption from urine stored in the urinary bladder has not been confirmed,
      however. Calcium is stored in bone and in specialized endolymphatic sacs. This
      Ca2+ can be mobilized when the need arises. There are a number of endocrine and
      other humoral factors that appear to be involved in amphibian calcium metabolism.
      These include parathyroid hormone, calcitonin, vitamin D and prolactin.

PMID- 8270857
TI  - Calcium handling by the mammalian kidney.
AB  - The mammalian kidney plays a crucial role in the Ca2+ homeostasis of the body. To
      maintain a net Ca2+ balance, more than 98% of the filtered load of Ca2+ must be
      reabsorbed along the nephron. There are two potential pathways through which net
      Ca2+ reabsorption can occur. First, a paracellular and passive route that
      predominates in the proximal tubules and thick ascending limb of Henle's loop.
      Second, a transcellular, active transport that characterises Ca2+ reabsorption in
      the distal nephron. Transcellular Ca2+ transport involves passive influx across
      the luminal membrane, diffusion through the cytosol and active extrusion across
      the peritubular membrane. The rate of active Ca2+ reabsorption is controlled by
      the calciotropic hormones, i.e. parathyroid hormone, calcitonin and 1,25
      dihydroxyvitamin D3. The application of new techniques in renal physiology has
      greatly increased our knowledge of the renal handling of Ca2+ and allowed the
      examination of Ca2+ transport processes at the cellular and subcellular level.
      This review focuses primarily on the mechanisms and regulation of transcellular
      Ca2+ transport. The distal nephron consists of at least four discrete segments
      and the contribution of each segment to active transcellular Ca2+ is discussed in
      detail.

PMID- 8270859
TI  - The human immunodeficiency virus-1 nef gene product: a positive factor for viral
      infection and replication in primary lymphocytes and macrophages.
AB  - Considerable controversy and uncertainty have surrounded the biological function
      of the Human Immunodeficiency Virus (HIV)-1 nef gene product. Initial studies
      suggested that this early, nonstructural viral protein functioned as a negative
      regulatory factor; thus, it was proposed to play a role in establishing or
      maintaining viral latency. In contrast, studies in Simian Immunodeficiency Virus
      (SIV)mac-infected rhesus monkeys have suggested that Nef is not a negative factor
      but rather plays a central role in promoting high-level viral replication and is
      required for viral pathogenesis in vivo. We sought to define a tissue culture
      system that would approximate the in vivo setting for virus infection in order to
      assess the role of HIV-1 Nef in viral replication. We show that infection of
      mitogen-activated peripheral blood mononuclear cells (PBMC) with Nef+ HIV results
      in enhanced replication as evidenced by earlier gag p24 expression when compared
      with infections performed with nef mutant viruses. Moreover, when unstimulated
      freshly isolated PBMC are infected with Nef+ and Nef- viruses and then
      subsequently activated with mitogen, the Nef-induced difference in viral
      replication kinetics is even more pronounced, with the Nef- viruses requiring
      much more time in culture for appreciable growth. A positive effect of Nef on
      viral replication was also observed in primary macrophages infected with a
      recombinant of YU-2, a patient-derived molecular clone with macrophage tropism.
      These positive effects of Nef on viral replication are dependent on the initial
      multiplicity of infection (MOI), in that infections of unstimulated PBMC at low
      MOI are most dependent upon intact nef for subsequent viral growth. We now
      provide evidence that the Nef+ HIV is more infectious than Nef- HIV from both a
      tissue culture infectious dose analysis, and a single-cell HIV infection assay.
      In the latter case, we demonstrate that infection with equivalent doses of HIV
      based on virion-associated gag p24 yields five- to sixfold more infected cells if
      Nef+ viral stocks were used. Furthermore, we find that the differential
      infectivity is not dependent on CD4 down-regulation as Nef+ virus produced from
      transfected COS cells lacking CD4 is also more infectious. However, normalization
      of PBMC infections to equivalent infectivity between that of the Nef+ and Nef-
      viruses continues to reveal delayed viral replication in the absence of Nef,
      suggesting that secondary viral spread in PBMC is also enhanced in Nef+
      infections. We demonstrate this directly by showing a 13-15-fold increase in
      infectivity of PBMC-derived Nef+ HIC.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270860
TI  - Reduced life span of anergic self-reactive B cells in a double-transgenic model.
AB  - The life span of anergic self-reactive B cells was determined by 5-bromo-2'
      deoxyuridine (BrdU) loading of tolerant double-transgenic (Dbl-Tg) mice produced
      by mating hen egg lysozyme (HEL)-transgenic mice with the corresponding
      immunoglobulin-transgenic (Ig-Tg) mice, the B cells of which express anti-HEL IgM
      and IgD. B cells from Dbl-Tg mice, despite being exposed to soluble antigen
      throughout their development, are not deleted, but persist in an anergic state.
      As a prelude to studying the life span of these anergic B cells, BrdU was
      administered to nontransgenic mice; B cells from the bone marrow, spleen, and
      lymph nodes displayed distinct kinetic profiles based on reciprocal expression of
      the B220 isoform of CD45 and heat-stable antigen (HSA). Thus, immature
      B220lo/HSAhi B cells incorporated BrdU rapidly suggesting recent generation from
      dividing precursors, whereas uptake by B cells expressing the mature B220hi/HSAlo
      phenotype was significantly slower, consistent with a longer life span. Such
      gating allowed analysis to be directed at the stable mature B cell population in
      transgenic mice. Comparison of BrdU uptake in Ig- and Dbl-Tg mice indicated that
      B cells from Dbl-Tg mice were renewed at a much higher rate (50% renewal times of
      0.64 vs. 3.4 wk for total B cells, and 1.2 vs. 5.0 wk for mature B200hi/HSAlo
      cells from Dbl- and Ig-transgenic mice, respectively). This difference was even
      more marked when analysis in Dbl-Tg mice was restricted to HEL-binding cells,
      which had a 50% renewal time of 3-4 d compared with 4-5 wk for non-HEL-binding B
      cells. While the proportion of B cells in cell cycle, and the rate of entry of
      newly generated B cells into the spleen of Ig- and Dbl-Tg mice, were similar, B
      cell numbers were reduced in Dbl-Tg mice. It was therefore concluded that anergic
      B cells have a markedly decreased life span in the periphery. According to
      studies in radiation chimeras produced by reconstituting HEL-transgenic
      recipients expressing different serum levels of antigen with Ig-Tg bone marrow,
      the reduced life span of anergic B cells was associated with the anergic state
      per se, the serum concentration of HEL being important only in attaining the
      critical threshold necessary for tolerance induction. B cells rendered tolerant
      by exposure to soluble self-antigen therefore survive for a relatively short
      period in an anergic state once they have reached peripheral lymphoid tissue and
      fail to enter the long-lived compartment.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270858
TI  - Zanvil Alexander Cohn 1926-1993.
AB  - Zanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on
      June 28, 1993. Cohn is best known as the father of the current era of macrophage
      biology. Many of his scientific accomplishments are recounted here, beginning
      with seminal studies on the granules of phagocytes that were performed with his
      close colleague and former editor of this Journal, James Hirsch. Cohn and Hirsch
      identified the granules as lysosomes that discharged their contents of digestive
      enzymes into vacuoles containing phagocytosed microbes. These findings were part
      of the formative era of cell biology and initiated the modern study of
      endocytosis and cell-mediated resistance to infection. Cohn further explored the
      endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in
      culture. He described vesicular inputs from the cell surface and Golgi apparatus
      and documented the thoroughness of substrate digestion within lysosomal vacuoles
      that would only permit the egress of monosaccharides and amino acids. These
      discoveries created a vigorous environment for graduate students, postdoctoral
      fellows, and junior and visiting faculty. Some of the major findings that emerged
      from Cohn's collaborations included the radioiodination of the plasma membrane
      for studies of composition and turnover; membrane recycling during endocytosis;
      the origin of the mononuclear phagocyte system in situ; the discovery of the
      dendritic cell system of antigen-presenting cells; the macrophage as a secretory
      cell, including the release of proteases and large amounts of prostaglandins and
      leukotrienes; several defined parameters of macrophage activation, especially the
      ability of T cell-derived lymphokines to enhance killing of tumor cells and
      intracellular protozoa; the granule discharge mechanism whereby cytotoxic
      lymphocytes release the pore-forming protein perforin; the signaling of
      macrophages via myristoylated substrates of protein kinase C; and a tissue
      culture model in which monocytes emigrate across tight endothelial junctions. In
      1983, Cohn turned to a long-standing goal of exploring host resistance directly
      in humans. He studied leprosy, focusing on the disease site, the parasitized
      macrophages of the skin. He injected recombinant lymphokines into the skin and
      found that these molecules elicited several cell-mediated responses. Seeing this
      potential to enhance host defense in patients, Cohn was extending his clinical
      studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician
      scientist who nurtured the relationship between cell biology and infectious
      disease.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270861
TI  - The T cell receptor repertoire of CD4-8+ thymocytes is altered by overexpression
      of the BCL-2 protooncogene in the thymus.
AB  - The bcl-2 gene encodes an intracellular, membrane-associated protein that
      protects immature cortical thymocytes from a wide variety of apoptotic stimuli,
      including glucocorticoids, radiation, and anti-CD3 treatment. Since cortical
      thymocytes are the primary target cells for thymic positive and negative
      selection processes, and since these processes are associated with cell death, we
      evaluated the role of bcl-2 in T cell development in two ways. In the first
      approach, transgenic mice expressing high levels of Bcl-2 in cortical thymocytes
      were mated with H-Y T cell receptor (TCR) transgenic mice, the latter being a
      well-defined system for the study of positive and negative selection of T cells.
      We found that the bcl-2 transgene had a dramatic effect on positive selection.
      This was manifested by a greatly increased production of mature thymocytes that
      were highly skewed towards the CD4-8+ lineage. The change involving CD4-8+
      thymocytes occurred not only in bcl-2 transgenic mice, but was also observed in H
      Y TCR/bcl-2 doubly transgenic mice, regardless of whether the H-Y TCR was
      expressed in the selecting (H-2b) or nonselecting (H-2d) environments.
      Furthermore, a large proportion of CD4-8+ thymocytes produced in H-2b H-Y TCR/bcl
      2 doubly transgenic female mice expressed endogenous TCR alpha chains rather than
      the transgenic TCR alpha chain. These observations are consistent with the model
      that high expression of Bcl-2 in cortical thymocytes overrides the normal
      apoptotic pathway. This then allows the selection of CD4-8+ thymocytes expressing
      TCRs that are otherwise nonselectable. However, the bcl-2 transgene did not
      protect CD4+8+ thymocytes expressing the male-specific TCR from deletion in male
      doubly transgenic mice. In the second approach, we determined the level of bcl-2
      mRNA expression in populations of thymocytes defined by their CD4/CD8 phenotypes
      using quantitative reversed transcriptase PCR techniques. Our results indicate
      that bcl-2 mRNA was expressed at a high level in immature CD4-8- thymocytes and
      in mature CD4+8- thymocytes. There is a dramatic downregulation of bcl-2 mRNA in
      CD4+8+ thymocytes, particularly those expressing a low level of TCR. CD4+8+
      thymocytes that upregulated their TCR, likely as a result of receiving positive
      selection signals, also upregulated bcl-2 mRNA. This observation suggests that
      rescue of immature thymocytes from the programmed cell death pathway by positive
      selection signals is accompanied by the upregulation of bcl-2 mRNA.

PMID- 8270862
TI  - Availability of endogenous peptides limits expression of an M3a-Ld major
      histocompatibility complex class I chimera.
AB  - Taking advantage of our understanding of the peptide specificity of the major
      histocompatibility complex class I-b molecule M3a, we sought to determine why
      these molecules are poorly represented on the cell surface. To this end we
      constructed a chimeric molecule with the alpha 1 and alpha 2 domains of M3a and
      alpha 3 of Ld thereby allowing use of available monoclonal antibodies to quantify
      surface expression. Transfected, but not control, B10.CAS2 (H-2M3b) cells were
      lysed readily by M3a-restricted monoclonal cytotoxic T lymphocytes. Thus, the
      chimera bound, trafficked, and presented endogenous mitochondrial peptides.
      However, despite high levels of M3a-Ld mRNA, transfectants were negative by
      surface staining. This finding was consistent with inefficient trafficking to the
      cell surface. Incubation at 26 degrees C, thought to permit trafficking of
      unoccupied heavy (H) chains, resulted in detectable cell surface expression of
      chimeric molecules. Incubation with exogenous peptide at 26 degrees C (but not at
      37 degrees C) greatly enhanced expression of M3a-Ld molecules in a dose-dependent
      manner, suggesting stabilization of unoccupied molecules. Stable association of
      beta 2-microglobulin with the chimeric H chain was observed in labeled cell
      lysates only in the presence of exogenous specific peptide, indicating that
      peptide is required for the formation of a ternary complex. These results
      indicate that surface expression of M3a-Ld is limited largely by the steady-state
      availability of endogenous peptides. Since most known M3a-binding peptides are N
      formylated, native M3a may normally be expressed at high levels only during
      infection by intracellular bacteria.

PMID- 8270864
TI  - The conditions of primary infection define the load of latent viral genome in
      organs and the risk of recurrent cytomegalovirus disease.
AB  - Recurrence of cytomegalovirus (CMV) from latency is a frequent cause of disease
      in immunocompromised patients. To date, there is no explanation for the diversity
      in the clinical manifestations. Primary infection can occur perinatally or later
      in life, and inevitably results in latent infection. Seropositivity for
      antibodies against CMV is indicative of latent infection, but is insufficient as
      a predictor for the risk of recurrence. As a model for this important medical
      problem, we compared the risks of murine CMV recurrence from latency established
      after neonatal primary infection and after infection at adult age. The risk of
      CMV recurrence was high only after neonatal infection. The copy number of latent
      viral genome in tissues was identified as the key parameter that determines the
      overall and organ-specific risks of recurrence. Latent CMV burden and risk of
      recurrence were related to the extent of virus multiplication during primary
      infection. The presence of latent CMV in multiple organs provides the molecular
      basis for stochastic events of recurrence in single organs or in any combination
      thereof. These findings are discussed as a concept of multifocal CMV latency and
      recurrence. It provides a rationale for the diversity in the clinical outcome of
      CMV disease.

PMID- 8270863
TI  - Defective development of thymocytes overexpressing the costimulatory molecule,
      heat-stable antigen.
AB  - Heat-stable antigen (HSA) is a small, glycosyl phosphatidylinositol-anchored
      protein that can act as a costimulatory molecule for antigen-dependent activation
      of helper T cells. In addition to being expressed on antigen-presenting B cells,
      HSA is also expressed during the initial stages of T cell development in the
      thymus. HSA levels are very high on immature CD4-, CD8- double negative
      thymocytes, but are reduced on CD4+, CD8+ double positive cells undergoing
      selection in the thymus, and are entirely eliminated when these cells
      differentiate into immunologically competent CD4+ or CD8+ single positive T
      cells. To examine the potential roles of this molecule in T cell development and
      selection, we generated transgenic mice in which HSA was highly expressed on all
      classes of thymocytes. The consequence of deregulated HSA expression was a
      pronounced reduction in the numbers of double positive and single positive
      thymocytes, whereas the numbers of their double negative precursors were largely
      unaffected. These results demonstrate that downregulation of HSA expression at
      the double positive stage is a critical event in thymocyte development. The
      depletion of thymocytes resulting from HSA overexpression begins at the same time
      as the onset of negative selection, suggesting that HSA may provide signals that
      contribute to determining the efficiency of this process.

PMID- 8270865
TI  - Development of the airway intraepithelial dendritic cell network in the rat from
      class II major histocompatibility (Ia)-negative precursors: differential
      regulation of Ia expression at different levels of the respiratory tract.
AB  - The relative inefficiency of respiratory mucosal immune function during infancy
      is generally attributed to the immaturity of the neonatal T cell system. However,
      immune competence in the adult lung has recently been shown to be closely linked
      to the functional capacity of local networks of intraepithelial dendritic cells
      (DC). This study examines the density and distribution of these DC throughout the
      neonatal respiratory tract in rats, focusing particularly on microenvironmental
      regulation of their class II major histocompatibility complex (MHC) (Ia)
      expression. In animals housed under dust-controlled conditions, airway epithelial
      and alveolar Ia+ DC detectable by immunostaining with the monoclonal antibody
      (mAb) Ox6 are usually not seen until day 2-3 after birth, and adult-equivalent
      staining patterns are not observed until after weaning. In contrast, the mAb Ox62
      detects large numbers of DC in fetal, infant, and adult rat airway epithelium.
      Costaining of these Ox62+ DC with Ox6 is rare in the neonate and increases
      progressively throughout infancy, and by weaning Ia+ DC comprised, on average,
      65% of the overall intraepithelial DC population. In infant rats, Ia+ DC are
      observed first at the base of the nasal turbinates, sites of maximum exposure to
      inhaled particulates, suggesting that their maturation is driven in part by
      inflammatory stimuli. Consistent with this suggestion, densitometric analysis of
      Ia staining intensity of individual DC demonstrates that by 2-3 d after birth, Ia
      expression by nasal epithelial DC was comparable with that of Iahigh epidermal
      Langerhans cells in adjacent facial skin, at a time when expression by tracheal
      epithelial DC was 7-10-fold lower. Additionally, the rate of postnatal appearance
      of Iahigh DC in the airway epithelium was increased by administration of
      interferon gamma, and decreased by exposure of infant rats to aerosolized
      steroid. These findings collectively suggest that Ia expression by neonatal
      respiratory tract DC is locally controlled and can be upregulated by mediators
      that are produced within the lung and airway epithelium in response to inhalation
      of proinflammatory stimuli. It was also noted that Ialow neonatal airway DC
      expressed adult equivalent levels of class I MHC, which suggests differences in
      capacity to prime for CD8(+)-dependent versus CD4(+)-dependent immunity to
      inhaled pathogens, during the early postnatal period.

PMID- 8270866
TI  - Conformational differences in major histocompatibility complex-peptide complexes
      can result in alloreactivity.
AB  - Mutations within the class I major histocompatibility complex (MHC) molecule that
      affect a peptide binding can result in strong allogeneic responses. It is
      believed this reflects, in part, binding of a different set of endogenous
      peptides by each MHC molecule. We have examined the representation of
      allopeptides recognized by Kb-specific cytotoxic T lymphocytes (CTL) clones among
      targets that express either the Kb or the Kbm8 mutant. These class I molecules
      mutationally differ by several residues at the base of the peptide binding groove
      resulting in lack of recognition of bm8 targets by most Kb-specific CTL, and in
      strong mutual alloreactivity. Since these differences involve pockets in the base
      of the peptide binding groove that are presumed to contribute to the affinity of
      peptide binding, and there is evidence for differences in peptide binding by the
      mutant and wild type molecule, it was considered most likely that alloreactivity
      was due to binding of different sets of peptides by each of these molecules.
      Surprisingly, the allopeptides recognized by Kb-specific clones from a variety of
      responders, including bm8, are often found associated with both the wild type and
      mutant class I molecules. Although for some allopeptides the amount of peptide
      normally found associated with bm8 is less than that associated with Kb,
      reactivity could not be restored by increasing the amount of the relevant
      peptide. Thus, the basis for much of the alloreactivity observed in this
      particular mutant and wild type combination is not the presence or absence of the
      relevant allopeptide but rather the different conformation adapted by the peptide
      MHC complex. These results allow us to conclude that strong alloreactive
      responses can result from T cell recognition of conformational differences
      between the stimulation and responder MHC molecules.

PMID- 8270867
TI  - Lymphoma models for B cell activation and tolerance. X. Anti-mu-mediated growth
      arrest and apoptosis of murine B cell lymphomas is prevented by the stabilization
      of myc.
AB  - Treatment of the WEHI-2131 or CH31 B cell lymphomas with anti-mu or transforming
      growth factor (TGF)-beta leads to growth inhibition and subsequent cell death via
      apoptosis. Since anti-mu stimulates a transient increase in c-myc and c-fos
      transcription in these lymphomas, we examined the role of these proteins in
      growth regulation using antisense oligonucleotides. Herein, we demonstrate that
      antisense oligonucleotides for c-myc prevent both anti-mu- and TGF-beta-mediated
      growth inhibition in the CH31 and WEHI-231 B cell lymphomas, whereas antisense c
      fos has no effect. Furthermore, antisense c-myc promotes the appearance of
      phosphorylated retinoblastoma protein in the presence of anti-mu and prevents the
      progression to apoptosis as measured by propidium iodide staining. Northern and
      Western analyses show that c-myc message and the levels of multiple myc proteins
      were maintained in the presence of antisense c-myc, results indicating that myc
      species are critical for the continuation of proliferation and the prevention of
      apoptosis. These data implicate c-myc in the negative signaling pathway of both
      TGF-beta and anti-mu.

PMID- 8270868
TI  - Membrane interactions influence the peptide binding behavior of DR1.
AB  - We analyzed the binding of an influenza matrix protein-derived peptide, MAT(17
      31), to cell surface and purified DR1. The pH dependence of peptide binding was
      dramatically influenced by the membrane environment. Cell surface binding was
      enhanced at low pH, with little or no binding detected at neutral pH and optimal
      binding at pH 4. By contrast, hydrogen ion concentration had minimal effect on
      peptide binding to purified DR1. Exposure to low pH in the absence of peptide did
      not affect the peptide binding capacity of cell-associated DR1. Purified DR1 was
      stable at low pH, excluding the possibility that enhanced binding was offset by a
      competing denaturation event at low pH. The striking effect of pH on peptide
      binding characteristic of cell surface DR1 was recovered after reconstitution of
      purified DR1 in B cell membranes by detergent dialysis. This behavior was
      partially recovered by reconstitution of full-length, but not truncated DR1 in
      vesicles containing purified lipid. Our results demonstrate that interactions
      involving membrane components influence the peptide-binding behavior of DR1.

PMID- 8270869
TI  - Somatic generation of hybrid antibody H chain genes in transgenic mice via
      interchromosomal gene conversion.
AB  - We have constructed lines of mice with transgenes containing an antibody heavy
      (H) chain variable region (VHDJH) gene and various amounts of natural
      immunoglobulin (Ig) and plasmid flanking DNA. In these lines, recombination of
      the transgene and the endogenous Igh locus takes place in B cells, leading to the
      expression of functional H chains partially encoded by the transgenic VHDJH gene.
      Here, we demonstrate that the transgenic VHDJH gene, and various amounts of
      flanking sequence are recombined with Igh locus DNA via interchromosomal gene
      conversion. The structures of the resulting "hybrid" transgene-Igh H chain loci
      are consistent with the 3' end of the conversion occurring in regions of sequence
      identity, and the 5' end taking place between regions of little or no homology.
      This mode of antibody transgene recombination with the Igh locus is fundamentally
      different from the previously reported "trans H chain class switching" that
      results in reciprocal translocations. In contrast, this recombination resembles
      events previously observed in mammalian tissue culture cells between adjacent
      homologous chromosomal sequences, or transfected DNA and a homologous chromosomal
      target. Our data indicate that this recombination takes place at a low frequency,
      and that the frequency is influenced by both the length and extent of homology
      between the transgene and the Igh locus, but is not greatly affected by transgene
      copy number. This recombination pathway provides a novel approach for the subtle
      alteration of the clonal composition of the mouse B cell compartment in vivo
      using VH genes with defined structures and functions.

PMID- 8270870
TI  - Neutrophils are essential for early anti-Listeria defense in the liver, but not
      in the spleen or peritoneal cavity, as revealed by a granulocyte-depleting
      monoclonal antibody.
AB  - This study shows that in mice selectively depleted of neutrophils by treatment
      with a monoclonal antibody, RB6-8C5, listeriosis is severely exacerbated in the
      liver, but not in the spleen or peritoneal cavity during the crucial first day of
      infection. At sites of infection in the livers of neutrophil-depleted mice,
      Listeria monocytogenes grew to large numbers inside hepatocytes. By contrast, in
      the livers of normal mice neutrophils rapidly accumulated at infectious foci and
      this was associated with the lysis of infected hepatocytes that served to abort
      infection in these permissive cells. In the spleen the situation was different,
      in that depletion of neutrophils did not result in appreciable exacerbation of
      infection. In this organ intact infected cells, many of which appeared to be
      fibroblast-like stromal cells, were found at foci of infection in the presence or
      absence of large numbers of neutrophils. This suggests that neutrophils are less
      effective at destroying L. monocytogenes-infected target cells in the spleen than
      in the liver. Consequently, at least during the first day, the organism remained
      free to multiply intracellularly in the spleen in cells that are permissive for
      its growth. Presumably, the same situation exists in the peritoneal cavity,
      because depleting neutrophils did not severely exacerbate infection initiated at
      this site.

PMID- 8270871
TI  - NADPH-binding component of the respiratory burst oxidase system: studies using
      neutrophil membranes from patients with chronic granulomatous disease lacking the
      beta-subunit of cytochrome b558.
AB  - The NADPH-binding site of the respiratory burst oxidase system of neutrophils has
      been proposed to be either at a cytosolic component or at the beta-subunit of
      cytochrome b558. In this study, affinity labeling of resting and stimulated
      membranes, the latter having been assembled by all of the oxidase components from
      both membrane and cytosol, was carried out using [32P]NADPH dialdehyde (oNADPH).
      Stimulation of human neutrophils with PMA greatly increased O2(-)-generating
      activity and caused considerable translocation of the cytosolic components
      p47phox and p67phox. Nevertheless, PMA stimulation did not produce a labeled band
      which included positions at 47, 67, and approximately 32 kD. The most intense
      band reflected a molecular mass of 84 kD regardless of the state of activation,
      but a labeled band was never found near the beta-subunit (91 kD) of cytochrome
      b558. This 84-kD protein was further confirmed in neutrophils of 14 patients with
      gp91phox-deficient X-linked chronic granulomatous disease. These results indicate
      that the NADPH-binding component is not recruited from the cytosol, and also,
      that a membranous redox component besides cytochrome b558 must be involved in the
      NADPH oxidase system.

PMID- 8270872
TI  - CD28-mediated costimulation of interleukin 2 (IL-2) production plays a critical
      role in T cell priming for IL-4 and interferon gamma production.
AB  - Naive T cells require interleukin 4 (IL-4) to develop into IL-4-producing T cells
      and IL-4 blocks development of such cells into interferon gamma (IFN-gamma)
      producers. Prior studies in accessory cell-independent priming systems using
      antireceptor antibodies as agonists have demonstrated that IL-2 is also necessary
      for the development of IL-4-producing cells under these culture conditions. Here
      we have examined the role of IL-2 and the CD28 costimulation pathway in priming
      for IL-4 and IFN-gamma production using a more physiologic model. This involved
      antigen presentation by accessory cells to naive CD4+ T cells from transgenic
      mice whose cells express a T cell receptor (TCR) specific for a cytochrome c
      peptide in association with I-Ek. With splenic antigen-presenting cells (APCs),
      inhibition of CD28 costimulation by the fusion protein CTLA4-immunoglobulin (Ig)
      blocked effective priming. Similarly, transfected fibroblasts expressing both MHC
      class II and the CD28 ligand B7 could prime for IL-4 production and such priming
      also was blocked by CTLA4-Ig. However, APCs deficient in CD28 ligands also could
      prime TCR transgenic T cells to become IL-4 producers if an exogenous source of
      IL-2, as well as IL-4, was provided, and the inhibition of priming seen with
      splenic or transfected fibroblast APCs in the presence of CTLA4-Ig could be
      reversed by addition of IL-2. Likewise, priming for IFN-gamma production could be
      blocked by CTLA4-Ig and reversed by IL-2. Thus, we conclude that IL-2 plays a
      critical role in priming naive CD4+ T cells to become IL-4 or IFN-gamma
      producers. Engagement of the CD28 pathway, although normally important in such
      priming, is unnecessary in the presence of exogenous IL-2.

PMID- 8270873
TI  - Continuous administration of anti-interleukin 10 antibodies delays onset of
      autoimmunity in NZB/W F1 mice.
AB  - We have previously shown that continuous administration of anti-interleukin 10
      (anti-IL-10) antibodies (Abs) to BALB/c mice modifies endogenous levels of
      autoantibodies, tumor necrosis factor alpha (TNF-alpha), and interferon gamma,
      three immune mediators known to affect the development of autoimmunity in "lupus
      prone" New Zealand black/white (NZB/W)F1 mice. To explore the consequences of IL
      10 neutralization in NZB/W F1 mice, animals were injected two to three times per
      week from birth until 8-10 mo of age with anti-IL-10 Abs or with isotype control
      Abs. Anti-IL-10 treatment substantially delayed onset of autoimmunity in NZB/W F1
      mice as monitored either by overall survival, or by development of proteinuria,
      glomerulonephritis, or autoantibodies. Survival at 9 mo was increased from 10 to
      80% in anti-IL-10-treated mice relative to Ig isotype-treated controls. This
      protection against autoimmunity appeared to be due to an anti-IL-10-induced
      upregulation of endogenous TNF-alpha, since anti-IL-10-protected NZB/W F1 mice
      rapidly developed autoimmunity when neutralizing anti-TNF-alpha Abs were
      introduced at 30 wk along with the anti-IL-10 treatment. Consistent with the
      protective role of anti-IL-10 treatment in these experiments, continuous
      administration of IL-10 from 4 until 38 wk of age accelerated the onset of
      autoimmunity in NZB/W F1 mice. The same period of continuous IL-10 administration
      did not appear to be toxic to, or cause development of lupus-like autoimmunity in
      normal BALB/c mice. These data suggest that IL-10 antagonists may be beneficial
      in the treatment of human systemic lupus erythematosus.

PMID- 8270874
TI  - Interleukin 7 promotes long-term in vitro growth of antitumor cytotoxic T
      lymphocytes with immunotherapeutic efficacy in vivo.
AB  - A major obstacle to the effective use of adoptive immunotherapeutic treatment of
      cancer is the difficulty of obtaining tumor-reactive lymphocytes in either
      sufficient numbers or with appropriate in vivo function to make such an approach
      feasible. Previous studies have shown that antitumor cytotoxic T lymphocytes
      (CTL) with in vivo efficacy can be generated in vitro from lymphoid cells
      obtained from lymph nodes that drain the anatomical site of a tumor. Results
      presented here demonstrate that inclusion of interleukin 7 (IL-7) into the medium
      in which such CTL are cultured can support their growth in vitro for prolonged
      periods of time in the absence of repeated stimulation with either tumor
      stimulator cells or tumor antigen. More importantly, antitumor CTL propagated in
      medium containing IL-7 have retained both their antigenic specificity and their
      ability to reject tumors in vivo subsequent to intravenous injection. Parallel
      cultures of antitumor CTL similarly cultured in medium containing only IL-2 could
      only be maintained for 5-6 wk, after which the number and proportion of viable
      cells that were recoverable from such cultures progressively decreased.
      Phenotypic analysis of CTL maintained after extended culture (i.e., 22 mo) in
      medium containing IL-7 demonstrated them to be CD3+4-8+ T cells. These cells were
      also found to express lymphocyte function associated 1, intercellular adhesion
      molecule 1, and Mel-14 cell interaction molecules. The data also demonstrate that
      these CTL do not require the presence of antigen-presenting cell populations to
      mount a proliferative response to tumor stimulator cells. Cells in these cultures
      were also demonstrated to produce IL-2 after stimulation with irradiated tumor
      cells, thereby indicating that these CTL have become independent of the
      requirement for CD4+ helper cells to survive and function either in vitro or in
      vivo. Collectively, the findings that IL-7 can beneficially augment the
      generation, and propagate the long-term growth, of antitumor CTL from lymph nodes
      draining a tumor site may have profound implications for promoting the
      immunotherapeutic treatment of cancer in humans.

PMID- 8270875
TI  - Transient increase in circulating gamma/delta T cells during Plasmodium vivax
      malarial paroxysms.
AB  - The percentage of peripheral blood mononuclear cells (PBMC) bearing the CD3+
      phenotype and the alpha/beta and gamma/delta T cell receptors (TCR) in PBMC were
      examined in Plasmodium vivax malaria patients and convalescents. The cells were
      labeled with monoclonal antibodies, stained with either fluorescence or
      phycoerythrin, and examined by ultraviolet (UV) microscopy. A highly significant
      increase in both the proportion and the absolute numbers of gamma/delta T cells
      (p < 0.005 and < 0.001, respectively, Student's t test) was observed in nonimmune
      P. vivax patients during clinical paroxysms compared to nonmalarial controls.
      These T cells, which normally constitute not more than 3-5% of PBMC, constituted
      < or = to 30% of PBMC during paroxysms in these nonimmune patients in whom the
      clinical symptoms were severe. A less significant increase of gamma/delta T cells
      were also observed in these nonimmune patients during infection, between
      paroxysms and during convalescence. In contrast, in an age-matched group of semi
      immune patients resident in a malaria-endemic region of the country, in whom the
      clinical disease was comparatively mild, there was no increase in gamma/delta T
      cells either during infection, even during paroxysms, or convalescence. The
      severity of disease symptoms in patients as measured by a clinical score
      correlated positively with the proportion of gamma/delta T cells in peripheral
      blood (r = 0.53, p < 0.01), the most significant correlation being found between
      the prevalence and severity of gastrointestinal symptoms, nausea, anorexia, and
      vomiting, and the proportion of gamma/delta T cells (r = 0.49, p = 0.002). These
      findings suggest that gamma/delta T cells have a role to play in the pathogenesis
      of malaria, possibly in the general constitutional disturbances and particularly
      in gastrointestinal pathology in malaria.

PMID- 8270876
TI  - The long-term maintenance of cytotoxic T cell memory does not require persistence
      of antigen.
AB  - I have used the transfer of primed lymphocytes into syngeneic irradiated
      recipients to investigate whether the persistence of antigen is required in the
      long-term maintenance of cytolytic T cell memory to influenza virus. Animals were
      immunized with influenza virus (A/WSN) and used 17 wk later as either donors for
      T cells or as lethally irradiated recipients. Naive age-matched mice served as
      controls. At intervals of 4, 8, 16, and 25 wk after T cell transfer, experimental
      and control groups were immunized with a heterologous virus (A/JAP) and
      splenocytes tested for lytic activity to influenza virus 3 and 6 d after
      immunization. Lytic activity 3 d after infection (a property exclusive to a
      memory cytotoxic T cell response) (Effros, R. B., J. Bennink, and P. C. Doherty.
      1978. Cell. Immunol. 36:345.; and Hill, A. B., R. V. Blanden, C. R. Parrish, and
      A. Mullbacher. 1992. Immunol. Cell Biol. 70:259), was only observed by primed and
      naive irradiated recipients reconstituted with memory T cells. No day 3 responses
      were observed when naive T cells were transferred into irradiated primed or
      unprimed recipients. These observations demonstrate that cytolytic T cell memory
      to influenza virus is long lived in the absence of antigen.

PMID- 8270877
TI  - CDR3 length in antigen-specific immune receptors.
AB  - In both immunoglobulins (Ig) and T cell receptors (TCR), the rearrangement of V,
      D, and J region sequence elements during lymphocyte maturation creates an
      enormous degree of diversity in an area referred to as the complementarity
      determining region 3 (CDR3) loop. Variations in the particular V, D, and J
      elements used, precise points of recombination, and random nucleotide addition
      all lead to extensive length and sequence heterogeneity. CDR3 loops are often
      critical for antigen binding in Igs and appear to provide the principal peptide
      binding residues in TCRs. To better understand the physical and selective
      constraints on these sequences, we have compiled information on CDR3 size
      variation for Ig H, L (kappa and lambda) and TCR alpha, beta, gamma, and delta.
      Ig H and TCR delta CDR3s are the most variable in size and are significantly
      longer than L and gamma chains, respectively. In contrast, TCR alpha and beta
      chain distributions are highly constrained, with nearly identical average CDR3
      lengths, and their length distributions are not altered by thymic selection.
      Perhaps most significantly, these CDR3 length profiles suggest that gamma/delta
      TCRs are more similar to Igs than to alpha/beta TCRs in their putative ligand
      binding region, and thus gamma/delta and alpha/beta T cells may have
      fundamentally different recognition properties.

PMID- 8270878
TI  - Loss of transporter protein, encoded by the TAP-1 gene, is highly correlated with
      loss of HLA expression in cervical carcinomas.
AB  - Malignant tumor cells can escape CD8+ cytotoxic T cell killing by downregulating
      class I major histocompatibility complex (MHC) expression. Stable class I MHC
      surface expression requires loading of the heavy chain/light chain dimer with
      antigenic peptide, which is delivered to class I MHC molecules in the endoplasmic
      reticulum by the presumed peptide transporter, encoded by the transporter
      associated with antigen presentation (TAP) 1 and 2 genes. We have investigated
      whether loss of class I MHC expression frequently observed in different cancers
      could result from interference with TAP function. A polyclonal antiserum, raised
      against a bacterial glutathione S-transferase/human TAP-1 fusion protein, was
      used for the immunohistochemical analysis of TAP-1 expression in 76 cervical
      carcinomas. Results showed loss of TAP-1 expression in neoplastic cells in 37 out
      of 76 carcinomas. Immunohistochemical double staining procedures in combination
      with HLA-specific antibodies revealed congruent loss at the single cell level of
      TAP-1 and HLA-A/B expression in 28 out of 37 carcinomas. The remaining samples
      expressed HLA(-A) in the absence of TAP-1 (n = 6) or showed loss of HLA(-A/B)
      while TAP-1 was expressed (n = 3). These data strongly indicate that inhibition
      of peptide transport by downregulation of TAP-1 is a potential strategy of
      malignant cells to evade immune surveillance.

PMID- 8270879
TI  - Cytokine-mediated regulation of chronic intestinal helminth infection.
AB  - Most inbred strains of mouse infected with the intestinal nematode Trichuris
      muris are resistant to infection expelling the parasite before adult worms
      establish. However, a few susceptible strains exist that are incapable of worm
      expulsion and harbor chronic infections of mature adult worms. Analyses of in
      vitro cytokine production by cells from the draining lymph node (mesenteric lymph
      node) have indicated that expulsion phenotype is tightly correlated with the
      selective expansion of helper T cells (Th) of the Th1 or Th2 cell subset within
      the mesenteric lymph node, resulting in susceptibility and resistance to T.
      muris, respectively. We have now confirmed and extended our in vitro observations
      in a series of experiments involving the in vivo manipulation of host cytokine
      levels. Depletion of interferon (IFN)-gamma in normally susceptible mice resulted
      in expulsion of the parasite, representing the first evidence for a role for IFN
      gamma in the establishment of chronic helminth infection. Blocking interleukin
      (IL)-4 function in normally resistant animals prevented the generation of a
      protective immune response allowing adult stages of the parasite to develop.
      Conversely the administration of IL-4 to a normally susceptible host facilitated
      expulsion and indeed enabled established adult worms to be expelled when
      administered late in infection. In all cases assessment of a variety of in vivo
      parameters indicative of a Th1- or Th2-type response (parasite-specific
      immunoglobulin (Ig) G2a and the parasite-specific IgG1, total IgE levels and
      intestinal mastocytosis, respectively) demonstrated that the in vivo modulation
      of a Th1- or Th2-specific cytokine allowed the reciprocal Th cell subset to
      expand and become dominant with dramatic consequences for worm expulsion.

PMID- 8270880
TI  - Efficient major histocompatibility complex class II-restricted presentation of
      measles virus relies on hemagglutinin-mediated targeting to its cellular receptor
      human CD46 expressed by murine B cells.
AB  - Measles virus after binding to its cell surface human CD46 receptor fuses with
      the plasma membrane. This fusion results in envelope hemagglutinin (H) and fusion
      glycoprotein (F) incorporated into the plasma membrane and injection of the
      nucleocapsid made of nucleoprotein (NP) into the cytosol. The influence of
      targeting measles virus (MV) to CD46 in the processing and presentation of MV H
      and NP to antigen specific MHC class II I-E(d)- and I-A(d)-restricted T cell
      hybridomas was explored using murine M12-CD46 B cell transfectants. Parent M12
      cells, which lack any MV receptor, were unable to present any of these two viral
      proteins when incubated with MV particles. Incubating M12.CD46 cells with 200 ng
      and 10 micrograms of MV could strongly stimulate H-specific and NP-specific T
      cells, respectively. Neosynthesis of MV proteins was not necessary since the
      efficiency of antigen presentation was similar when using ultraviolet-inactivated
      MV. Similar enhancing effects (more than 1,000-fold) on antigen presentation were
      also observed when using purified native H soluble or incorporated into liposomes
      whereas denaturating H glycoprotein resulted in a poor efficiency in T cell
      stimulation, M12.CD46 being no more potent than the parental M12 counterpart. MV
      H and NP presentation efficiency did not depend on MV fusion with plasma membrane
      as revealed by the lack of effect of specific fusion inhibitors. Both MV H and NP
      presentations were sensitive to chloroquine inhibition indicating that antigens
      from CD46-mediated captured MV were likely processed in the endosome/lysosome
      compartment. Altogether these data indicate that (a) MV targeting via CD46 has a
      strong effect on the efficiency of antigen presentation by MHC class II, (b) the
      effect is mediated by the binding of H to CD46, and (c) though MV does fuse with
      plasma membrane, endocytosis, and processing of virus particles are also
      occurring. Since, in humans, CD46 is expressed in almost every tissue including
      professional antigen-presenting cells, such a targeting is likely to play a
      crucial role in the CD4+ T cell-mediated primary immune response against the
      pathogen in vivo.

PMID- 8270881
TI  - Preferential usage of the Fc receptor gamma chain in the T cell antigen receptor
      complex by gamma/delta T cells localized in epithelia.
AB  - zeta and eta chains of the T cell antigen receptor (TCR) complex and the gamma
      chain of Fc receptors (FcR gamma) constitute a family of proteins important for
      the expression of, and signal transduction through, these receptors in
      hematopoietic cells. In zeta-deficient mice, TCR expression was reduced in most T
      cells. By contrast, CD8 alpha alpha + TCR-gamma/delta + intestinal
      intraepithelial lymphocytes in these mice expressed a normal level of TCR.
      Biochemical analysis of the TCR complex in these cells from zeta-deficient as
      well as normal mice revealed the predominant usage of FcR gamma. Furthermore,
      gamma/delta + T cells in epithelia of the skin and female reproductive organs
      from zeta-deficient mice also showed relatively high TCR expression, indicating
      the usage of FcR gamma. These observations demonstrate the preferential usage of
      FcR gamma by gamma/delta + T cells localized in epithelia of normal mice.

PMID- 8270882
TI  - Enhancer-dependent and -independent steps in the rearrangement of a human T cell
      receptor delta transgene.
AB  - The rearrangement and expression of T cell receptor (TCR) gene segments occurs in
      a highly ordered fashion during thymic ontogeny of T lymphocytes. To study the
      regulation of gene rearrangement within the TCR alpha/delta locus, we generated
      transgenic mice that carry a germline human TCR delta minilocus that includes V
      delta 1, V delta 2, D delta 3, J delta 1, J delta 3, and C delta segments, and
      either contains or lacks the TCR delta enhancer. We found that the enhancer
      positive construct rearranges stepwise, first V to D, and then V-D to J.
      Construct V-D rearrangement mimics a unique property of the endogenous TCR delta
      locus. V-D-J rearrangement is T cell specific, but is equivalent in alpha/beta
      and gamma/delta T lymphocytes. Thus, either there is no commitment to the
      alpha/beta and gamma/delta T cell lineages before TCR delta gene rearrangement,
      or if precommitment occurs, it does not operate directly on TCR delta gene cis
      acting regulatory elements to control TCR delta gene rearrangement. Enhancer
      negative mice display normal V to D rearrangement, but not V-D to J
      rearrangement. Thus, the V-D to J step is controlled by the enhancer, but the V
      to D step is controlled by separate elements. The enhancer apparently controls
      access to J delta 1 but not D delta 3, suggesting that a boundary between two
      independently regulated domains of the minilocus lies between these elements.
      Within the endogenous TCR alpha/delta locus, this boundary may represent the 5'
      end of a chromatin regulatory domain that is opened by the TCR delta enhancer
      during T cell development. The position of this boundary may explain the unique
      propensity of the TCR delta locus to undergo early V to D rearrangement. Our
      results indicate that the TCR delta enhancer performs a crucial targeting
      function to regulate TCR delta gene rearrangement during T cell development.

PMID- 8270883
TI  - Rat T cell response to superantigens. I. V beta-restricted clonal deletion of rat
      T cells differentiating in rat-->mouse chimeras.
AB  - T cells of mice display V beta-specific reactivity for a spectrum of mouse
      mammary tumor virus (Mtv) antigens; confrontation with these antigens during
      ontogeny causes substantial "holes" in the T cell repertoire. Since endogenous
      Mtv antigens are rare in other species, the question arises whether V beta
      specific recognition of Mtv antigens is unique to mice. To examine this question,
      rat T cells were allowed to differentiate from stem cells in severe combined
      immunodeficiency (SCID) mice. These rat-->mouse xenochimeras were prepared under
      a variety of conditions. The results show that rat T cells are strongly reactive
      to mouse Mtv antigens, both in terms of tolerogenicity and immunogenicity. In
      fact, the V beta specificity of rat and mouse T cells for Mtv antigens is almost
      indistinguishable.

PMID- 8270884
TI  - Rat T cell responses to superantigens. II. Allelic differences in V beta 8.2 and
      V beta 8.5 beta chains determine responsiveness to staphylococcal enterotoxin B
      and mouse mammary tumor virus-encoded products.
AB  - The previous paper in this series demonstrates that rat T cells developing de
      novo in the presence of mouse mammary tumor virus (Mtv) antigens in rat-->severe
      combined immunodeficiency (SCID) mouse xenochimeras display a distinct pattern of
      V beta-restricted deletion; this deletion pattern is remarkably similar to that
      occurring during thymic development of mouse T cells in Mtv+ strains. In
      addition, T cells developing in the absence of Mtv antigens in these rat-->mouse
      xenochimeras are tolerant of host antigens, but show strong primary proliferative
      responses in cultures stimulated with Mtv-7+ (Mlsa) mouse cells; like the mouse,
      these rat T cell responses are dominated by V beta 6 and V beta 8 T cells. Here,
      we continue analysis of rat T cell responses to superantigens; we show that T
      cells from Lewis and Fischer 344 rats expressing V beta 8.2 display an important
      all-or-nothing difference in their responses to Mtv-7 superantigens. This all-or
      none strain difference in the response to Mtv-7 applies also to the response by V
      beta 8.2 and V beta 8.5 T cells to the soluble superantigen staphylococcal
      enterotoxin B. Because these two rat strains express different alleles of these
      two V beta 8 family members, this finding identifies additional, hitherto
      unreported residues of the T cell receptor beta chain important in T cell
      responses to superantigens.

PMID- 8270885
TI  - Distinct types of lung disease caused by functional subsets of antiviral T cells.
AB  - T cells appear to play a central role in viral bronchiolitis, but the effects of
      different functional and phenotypic subgroups of T cells have not been defined.
      To test the activities of T cells recognizing individual proteins of respiratory
      syncytial (RS) virus, virus-specific T cell lines were produced from mice primed
      by scarification with recombinant vaccinia viruses expressing the major surface
      glycoprotein (G), fusion protein (F) or second matrix (22K) protein of RS virus.
      As previously reported, the in vitro characteristics of these cells are
      predetermined by the choice of RS virus protein: 22K-specific cells are
      predominantly class I-restricted cytolytic CD8+ cells; F-specific cells, a
      mixture of cytolytic CD8+ cells and CD4+ cells with a T helper 1 cell (Th1)
      cytokine secretion profile, whereas those from G-sensitized mice are almost
      exclusively CD4+, with Th2 characteristics. Mice infected intranasally with RS
      virus showed mild illness and recovered fully, but developed respiratory distress
      after intravenous injections of T cells. Dose-for-dose, infected mice receiving G
      specific cells suffered the most severe (sometimes fatal) illness, characterized
      by lung hemorrhage, pulmonary neutrophil recruitment (shock lung) and intense
      pulmonary eosinophilia. This disease was further enhanced by coinjection of 22K
      specific cells, which alone caused mild shock lung without eosinophilia. F
      specific cells caused minimal enhancement of pathology and had little or no
      effect on the disease caused by G-specific cells. Each cell line reduced lung
      virus titer and combined injections of G- and 22K-specific cells eliminated
      infection completely. The in vitro characteristics of these antiviral T cell
      lines therefore predict the pathological effects in vivo. Moreover, different
      forms of viral bronchiolitis can be caused by functionally distinct types of
      activated T cell.

PMID- 8270886
TI  - Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia
      cells.
AB  - Recent studies have established that interleukin (IL)-10 induces growth and most
      notably differentiation of normal human B lymphocytes. We studied here the
      effects of IL-10 on the proliferation and survival of B-chronic lymphocytic
      leukemia (B-CLL) cells. IL-10 was found to inhibit 54-96% of the spontaneous
      tritiated thymidine incorporation observed in 3 of 12 B-CLL samples. Furthermore,
      IL-10 decreased the viable cell recovery of all five B-CLL samples tested,
      irrespective of whether cells were spontaneously synthesizing DNA or not. After 1
      wk, B-CLL populations cultured with IL-10 were lost while those cultured without
      IL-10 survived. Flow cytometric analysis, DNA gel electrophoresis, and Giemsa
      staining all revealed that IL-10 induced B-CLL cells to die from apoptosis. This
      IL-10-mediated apoptosis was dose dependent and specific as it could be inhibited
      by a neutralizing anti-IL-10 antibody. B-CLL cells undergoing apoptosis in
      response to IL-10 showed decreased Bcl-2 protein levels. Addition of IL-2, IL-4,
      interferon gamma, and anti-CD40 monoclonal antibody prevented the IL-10-mediated
      apoptosis of B-CLL cells. None of the malignant B cell populations obtained from
      eight non-Hodgkin's lymphomas and three hairy cell leukemias underwent apoptosis
      after IL-10 treatment, thus suggesting that the apoptotic effect of IL-10 is
      specific for B-CLL cells. Thus, IL-10 inhibits the DNA synthesis and most notably
      the survival of B-CLL cells, findings that call for considering IL-10 in the
      immunotherapy of chemoresistant B-CLL.

PMID- 8270887
TI  - Access to word meanings during spoken language comprehension: effects of
      sentential semantic context.
AB  - In 3 cross-modal priming experiments, we investigated whether access to a word's
      meaning is affected by the semantic context in which it is heard or is exhaustive
      and context-independent. We probed access of nonassociated semantic properties
      and normatively associated words before and after prime offset. Whereas
      associated targets were primed context-independently, access to semantic property
      targets was affected by the sentential context. Semantic property targets showed
      greater priming in a sentence biasing to a specific semantic property than in a
      neutral condition, even when this bias made the target property irrelevant rather
      than relevant. These results cannot be accounted for by current exhaustive access
      or context-dependency theories of lexical access.

PMID- 8270888
TI  - Sequential and coordinative complexity: age-based processing limitations in
      figural transformations.
AB  - Dimensions of cognitive complexity in figural transformations were examined in
      the context of adult age differences. Sequential complexity was manipulated
      through figural transformations of single objects in a multiple-object array.
      Coordinative complexity was induced through spatial or nonspatial transformations
      of the entire array. Results confirmed the prediction that age-related slowing is
      larger in coordinative complexity than in sequential complexity conditions. The
      effect was stable across 8 sessions (Experiment 1), was obtained when age groups
      were equated in accuracy with criterion-referenced testing (Experiment 2), and
      was corroborated by age-differential probabilities of error types (Experiments 1
      and 2). A model is proposed attributing age effects under coordinative complexity
      to 2 factors: (a) basic-level slowing and (b) time-consuming reiterations through
      the processing sequence due to age-related working memory failures.

PMID- 8270889
TI  - Acquiring bimanual skills: contrasting forms of information feedback for
      interlimb decoupling.
AB  - The present experiments addressed the learner's capability to perform different
      upper-limb actions simultaneously with the help of various sources of information
      feedback. An elbow flexion movement was made in the left limb together with a
      flexion-extension-flexion movement in the right limb. Interlimb interactions were
      assessed at the structural as well as the metrical level of movement
      specification during acquisition and retention. Despite a strong initial tendency
      for the limbs to be synchronized, findings revealed that Ss became gradually more
      successful in interlimb decoupling as a result of practice with augmented
      feedback. However, detailed knowledge of movement kinematics was no more
      effective than global outcome information for interlimb decoupling, indicating
      that knowledge of results may have more potential for acquiring multiple degree
      of-freedom tasks than previously believed. Finally, the data support the general
      notion that learning new coordination tasks involves the suppression of
      preexisting preferred coordination tendencies, which is often a prerequisite for
      building new coordination modes.

PMID- 8270890
TI  - Boundary extension: fundamental aspect of pictorial representation or encoding
      artifact?
AB  - Viewers remember seeing more of a scene than was actually depicted in a
      photograph, a phenomenon called boundary extension (H. Intraub & M. Richardson,
      1989). We tested whether prior warning would eliminate this distortion, by having
      81 Ss view 12 photographs of simple scenes for 15 s each after receiving 1 of 3
      encoding instructions. All subjects were told to remember each picture in detail.
      Control Ss received no additional information. Test-informed Ss received prior
      warning about the type of tests. Demo Ss experienced a demonstration of the
      phenomenon and were instructed to guard against it. After presentation, a drawing
      task and a boundary recognition test were administered. Prior warning sometimes
      reduced, but never eliminated, boundary extension. We suggest the phenomenon
      reflects activation of scene expectations during perception.

PMID- 8270891
TI  - TODAM and the list-strength and list-length effects: comment on Murdock and
      Kahana (1993a).
AB  - B. B. Murdock and M. J. Kahana (1993a) presented a continuous memory version of
      the theory of distributed associative memory (TODAM) model; they claimed that
      this model predicts list-strength and list-length findings, including those
      reported by R. Ratcliff, S. E. Clark, and R. M. Shiffrin (1990) and K. Murnane
      and R. M. Shiffrin (1991a). This model is quite similar to one discussed by R. M.
      Shiffrin, R. Ratcliff, and S. Clark (1990), who rejected the model on the basis
      of its inability to predict both an absent or negative list-strength effect (when
      strength is varied by repetitions) and a present list-length effect. In this
      comment we elaborate the earlier discussion and demonstrate that the version of
      TODAM proposed by B. B. Murdock and M. J. Kahana (1993a) indeed fails for this
      reason. We show this first for a somewhat simplified version of the model for
      which derivations are obvious and then in a simulation of the complete version
      using the parameter values suggested by B. B. Murdock and M. J. Kahana (1993a).

PMID- 8270892
TI  - At high dietary levels ethanol alters the structure of mid- and hindgut
      epithelial cells of Drosophila melanogaster larvae.
AB  - The midgut of Drosophila melanogaster is a site of alcohol dehydrogenase (ADH)
      activity, the enzyme that catalyzes the first step in the major pathway for
      ethanol degradation. The effects of different levels of dietary ethanol on the
      ultrastructures of the guts of larvae of the Canton-S wild-type strain and the
      ADH-deficient, Adhn2, strain were ascertained. In wild-type larvae fed an ethanol
      free, defined medium, the foregut epithelium was characterized by few glycogen
      rosettes and sparse microvilli that protruded into the gut's thick lumen lining.
      The midgut epithelium was typical of cells involved in absorption and active
      transport with abundant microvilli on the apical surface and membrane infoldings
      on the basal surface. In place of microvilli, the apical surface of the hindgut
      had membrane infoldings. The apical surfaces of both the mid- and hindgut
      epithelium were covered by a thick, electron-dense peritrophic membrane
      consisting of chitin. In both strains the subcellular damage that was correlated
      with ethanol levels in the diet was confined to the midgut and hindgut regions.
      Damage to gut cells in the form of disrupted mitochondria, dilated rough
      endoplasmic reticulum, low densities of glycogen rosettes and protein granules,
      high numbers of autophagic vacuoles, and the presence of myelin whirls was
      extensive in Canton-S strain larvae fed a high ethanol diet. A low dietary
      concentration of ethanol induced changes in gut ultrastructure of Adhn2 larvae
      similar to the changes that were observed in wild-type larvae fed the higher
      ethanol concentrations, but the basal infoldings were more dilated in the Adhn2
      larvae. At high dietary concentrations the disruption of mid- and hindgut cells
      by ethanol appeared great enough to interfere with the digestion and absorption
      of nutrients.

PMID- 8270893
TI  - Cyclic postural behavior in the crayfish, Procambarus clarkii: properties of the
      pattern-initiating network.
AB  - Crayfish exhibit complex cyclical adjustments in abdominal posture during certain
      forms of backward walking. An isolated nerve cord preparation was used to
      investigate the properties of the interneurons which direct this alternation of
      abdominal flexion and extension. The command function for this cyclic postural
      behavior appears to be the domain of a distributed network of multiple pattern
      initiating interneurons: each interneuron may be viewed as a command element
      within a command system. The cyclic pattern may be elicited by stimulation of
      small axon bundles pulled from the ventrolateral margins of any of the abdominal
      connectives. As few as one stimulus pulse to the axon bundle can elicit a single
      cycle of patterned output, although more pulses are generally necessary. This
      suggests some convergence or amplification step in the pattern-initiating
      interneurons. The amplification may be accomplished by several pattern-initiating
      interneurons that are coupled to one another and converge on pattern generating
      circuits in each ganglion. Evidence supporting this interpretation is presented.
      Experiments involving resection of the cord reveal that the pattern-initiating
      signals transfer laterally across all of the abdominal ganglia, but the network
      contains a bias for descending signal conduction once a lateral transfer is made.
      This finding agrees with other results. For example, recordings from pattern
      initiating axon bundles at rostral and caudal locations in the abdominal nerve
      cord show several descending but only one ascending unit activated during cyclic
      pattern generation. We also show that an isolated ganglion is capable of
      producing the cyclic motor program, although the outputs are much weaker than
      those elicited in the intact abdominal cord. Therefore, the pattern-initiating
      system is both central and distributed.

PMID- 8270894
TI  - Calcium control of metamorphosis in polychaete larvae.
AB  - The importance of Ca2+ in the control of metamorphosis of a marine invertebrate
      larva was investigated. An excess of [Ca2+] in the external medium induced
      metamorphosis of Phragmatopoma californica (polychaete) larvae in a concentration
      dependent manner. This effect is specific for calcium, and not simply the result
      of osmotic changes, as an excess of Mg2+ did not induce metamorphosis. Consistent
      with this finding, the calcium ionophore, A23187, also induced metamorphosis in a
      concentration-dependent manner. Paradoxically, however, the aromatic compounds
      diltiazem, verapamil, D600, and nifedipine, known to block Ca2+ channels in other
      systems, also induced metamorphosis. When exposed to diltiazem for only 20 h and
      subsequently washed free of this compound, 95% of the larvae metamorphosed and
      developed normally. Previous studies have demonstrated that the induction of
      metamorphosis in Phragmatopoma californica is controlled by chemosensory
      recognition of an exogenous morphogen and mediated by an excitatory pathway that
      involves adenyl cyclase and cyclic AMP. Because cellular excitation and cyclic
      AMP-dependent signal transduction generally involve the participation of calcium
      ion, the most parsimonious explanation for the results reported here include (1)
      direct control of the morphogenetic pathway by calcium ion, and (2) complexities
      of the calcium regulation of this process, or a functional similarity between the
      structurally related aromatic effectors tested and the natural inducer of
      metamorphosis.

PMID- 8270895
TI  - Locations of the ectodermal and nonectodermal subdivisions of the epiblast at
      stages 3 and 4 of avian gastrulation and neurulation.
AB  - A prospective fate map of the avian epiblast at late gastrula and early neurula
      stages has been generated through the construction of quail/chick transplantation
      chimeras. This map shows the subdivisions of the prospective ectoderm, mesoderm,
      and endoderm, both within the epiblast prior to their ingression and within the
      primitive streak. The map demarcates the locations and extents of the prospective
      surface ectoderm, otic placodes, neural crest, and neural plate--including its
      postnodal levels--in prospective ectoderm of the epiblast; prospective foregut,
      within the prospective endoderm of the epiblast and primitive streak; and
      prospective notochord, somites, intermediate mesoderm, lateral plate mesoderm,
      and extraembryonic mesoderm in the prospective mesoderm of the epiblast and/or
      primitive streak. Prospective cardiogenic cells are apparently absent from the
      primitive streak at these stages, and contributions of the epiblast to the heart
      are relatively scant and inconsistent with the expected timing and directions of
      migrations of prospective cardiogenic cells. Mapping of the primitive streak at
      earlier stages in another study (Garcia-Martinez and Schoenwolf: Developmental
      Biology, in press) reveals that the ingression of cardiogenic cells through the
      primitive streak occurs prior to late gastrula stages, suggesting that
      contributions of epiblast to the heart at later stages are artifactual. Tests of
      prospective potency, based on the projected locations of origin of various cell
      groups provided by the new prospective fate map, are underway.

PMID- 8270897
TI  - Tests of the ability of two-cell mouse embryos to utilize selected precursors of
      phosphoenolpyruvic acid and pyruvic acid.
AB  - Phosphoenolpyruvic acid and pyruvic acid are among the few compounds that two
      cell mouse embryos have been found capable of using as energy sources; most of
      the compounds in the glycolytic pathway and Krebs cycle that have been tested
      have been found unusable. Because 3-phosphoglyceric acid is the compound
      converted most directly to phosphoenolpyruvic acid in glycolysis, one objective
      of this study was to examine whether it could support development of two-cell
      embryos as phosphoenolpyruvic acid can. An additional objective was to examine
      whether alanine or serine, two amino acids that in later stages of development
      are converted to pyruvic acid for entry into the Krebs cycle, could support
      development of two-cell embryos as pyruvate does. Two-cell embryos were obtained
      from the oviducts of mice (C57BL x CBA) and were cultured in medium that
      contained 3-phosphoglyceric acid, alanine, or serine in lieu of the pyruvate,
      lactate, and glucose usually contained in the medium. The embryos failed to
      undergo cleavage but this was not attributable to only a single energy source
      having been provided; embryos developed in a medium that provided only pyruvate.
      The results suggest that mouse embryos at the two-cell stage of development are
      either unable to transport 3-phosphoglyceric acid, alanine, and/or serine or are
      unable to convert the compounds to chemically similar ones, phosphoenolpyruvic
      acid or pyruvic acid, which can be metabolized by two-cell mouse
      embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8270896
TI  - Formation of distal structures from stumps of chick wing buds at stages 24-25
      following the grafting of quail tissue from X-irradiated distal limb buds.
AB  - To examine the regulatory activity of the proximal region of chick limb buds,
      distal halves of chick wing buds at stages 24-25 were removed, and the distal
      tips of X-irradiated stage 21 quail limb buds with an apical ectodermal ridge
      (AER) were grafted onto the chick stumps. The host stumps formed only humerus
      after removal of the donor distal tips or with tip mesoderm alone. However, when
      distal tips with an AER were grafted onto the stumps, one or two cartilage
      elements of host origin were formed at the distal end of the humerus. To examine
      whether the stump cells have changed to cells of a more distal, progress zone
      (PZ) cells, the chick stumps with quail tips were immunostained with antibody
      against AV-1, which reacts with the anterior PZ region of chick limb buds and is
      specific for an antigen that is expressed under the control of the AER. Within
      two days of grafting, cells positive for the antigen reappeared in the stump
      tissues. These results suggest that the some of the stump cells may be converted
      to PZ cells and their positional values may change to those of more distal
      structures under the influence of the AER.

PMID- 8270898
TI  - Limitations in measuring the quality of health care.

PMID- 8270899
TI  - More about generalists.

PMID- 8270900
TI  - Pediatric approach to prevention of coronary heart disease.
AB  - Management of children with hypercholesterolemia has proven to be a controversial
      issue. The appropriate approach is to test those at highest risk for premature
      coronary heart disease most likely to benefit from intervention. Recommendations
      are reviewed in the context of the National Cholesterol Education Program Expert
      Panel on Blood Cholesterol Levels in Children and Adolescents. An overview is
      provided of the problem of preventing coronary heart disease through childhood
      intervention.

PMID- 8270902
TI  - New frontiers in critical care medicine.
AB  - Critical care medicine integrates various treatment modalities to provide care of
      patients with multiple system dysfunction or failure and to determine the
      diagnosis of the particular condition. The pulmonary artery catheter advanced
      from a simple tool to measure intracardiac pressures and output to methodology
      enabling clinicians to understand the balance between oxygen delivery and
      utilization. Critical care developed new concepts in the treatment of respiratory
      failure including not only forms of mechanical ventilation such as pressure
      control but also methods such as ECMO and surfactant therapy which may preclude
      the need for mechanical ventilation or minimize its needs. Sepsis represents the
      greatest problem in caring for the critically ill. Continued development of
      genetically engineered drugs may ultimately improve survival and reduce
      complications. Critical care has become a subspecialty, synthesizing the basic
      knowledge from anesthesiology, internal medicine, pediatrics and surgery. Its
      multidisciplinary delivery represents the way of the future.

PMID- 8270901
TI  - Recasting Florida's insanity defense. Two modest proposals.
AB  - Three states have established psychiatric security review boards mandated to
      primarily provide protection from the potentially destructive behavior of
      insanity acquitees. Each year in Florida there are 100 of these patients; 5% have
      been involved in capital offenses. These boards, as compared with the extant
      judiciary system, are more effective and parsimonious and serve the end of
      primary prevention. It is recommended that the plea, "not guilty by reason of
      insanity," be changed to "guilty but insane." The change is largely semantic but
      should result in greater prosecutorial and public acceptance of the insanity plea
      and be more in keeping with individual freedom for patients as provided under the
      Constitution.

PMID- 8270903
TI  - Supreme Court decisions to impact physician defendants.

PMID- 8270904
TI  - Mechanism of glucocorticoid action.
AB  - Glucocorticoids are steroid hormones synthesized by the adrenal cortex that are
      important in regulating many physiological and developmental processes. Because
      of anti-inflammatory and immunosuppressant effects, they are widely used to treat
      a variety of disorders. Their action occurs because of binding to the receptor in
      responsive cell types. The receptor protein consists of specific domains, each
      required for specific functions. The steroid: receptor complex migrates to the
      nucleus, binds to specific regions of DNA called glucocorticoid response
      elements, and either stimulates or inhibits the expression of specific genes. A
      cell's response depends upon the availability of hormone, transport proteins,
      affinity and number of intracellular receptors. Several mechanisms that in vivo
      appear to influence the number of functional receptors within a responsive cell
      have been defined. These are autoregulation of receptor synthesis, modulation of
      receptor phosphorylation, and regulation of receptor levels by factors that
      mediate other signal transduction pathways.

PMID- 8270905
TI  - Tort law 101.

PMID- 8270907
TI  - Physician credibility at risk.

PMID- 8270906
TI  - Managed care and academic medicine.

PMID- 8270908
TI  - Pre-steady-state charge translocation in NaK-ATPase from eel electric organ.
AB  - Time-resolved measurements of charge translocation and phosphorylation kinetics
      during the pre-steady state of the NaK-ATPase reaction cycle are presented. NaK
      ATPase-containing microsomes prepared from the electric organ of Electrophorus
      electricus were adsorbed to planar lipid bilayers for investigation of charge
      translocation, while rapid acid quenching was used to study the concomitant
      enzymatic partial reactions involved in phosphoenzyme formation. To facilitate
      comparison of these data, conditions were standardized with respect to pH (6.2),
      ionic composition, and temperature (24 degrees C). The different phases of the
      current generated by the enzyme are analyzed under various conditions and
      compared with the kinetics of phosphoenzyme formation. The slowest time constant
      (tau 3(-1) approximately 8 s-1) is related to the influence of the capacitive
      coupling of the adsorbed membrane fragments on the electrical signal. The
      relaxation time associated with the decaying phase of the electrical signal (tau
      2(-1) = 10-70 s-1) depends on ATP and caged ATP concentration. It is assigned to
      the ATP and caged ATP binding and exchange reaction. A kinetic model is proposed
      that explains the behavior of the relaxation time at different ATP and caged ATP
      concentrations. Control measurements with the rapid mixing technique confirm this
      assignment. The rising phase of the electrical signal was analyzed with a kinetic
      model based on a condensed Albers-Post cycle. Together with kinetic information
      obtained from rapid mixing studies, the analysis suggests that electroneutral ATP
      release, ATP and caged ATP binding, and exchange and phosphorylation are followed
      by a fast electrogenic E1P-->E2P transition. At 24 degrees C and pH 6.2, the rate
      constant for the E1P-->E2P transition in NaK-ATPase from eel electric organ is >
      or = 1,000 s-1.

PMID- 8270909
TI  - Activation of Ca(2+)-dependent K+ current by acetylcholine and histamine in a
      human gastric epithelial cell line.
AB  - The effects of acetylcholine (ACh) and histamine (His) on the membrane potential
      and current were examined in JR-1 cells, a mucin-producing epithelial cell line
      derived from human gastric signet ring cell carcinoma. The tight-seal, whole cell
      clamp technique was used. The resting membrane potential, the input resistance,
      and the capacitance of the cells were approximately -12 mV, 1.4 G ohms, and 50
      pF, respectively. Under the voltage-clamp condition, no voltage-dependent
      currents were evoked. ACh or His added to the bathing solution hyperpolarized the
      membrane by activating a time- and voltage-independent K+ current. The ACh
      induced hyperpolarization and K+ current persisted, while the His response
      desensitized quickly (< 1 min). These effects of ACh and His were mediated
      predominantly by m3-muscarinic and H1-His receptors, respectively. The K+ current
      induced by ACh and His was inhibited by charybdotoxin, suggesting that it is a
      Ca(2+)-activated K+ channel current (IK.Ca). The measurement of intracellular
      Ca2+ ([Ca2+]i) using Indo-1 revealed that both agents increased [Ca2+]i with
      similar time courses as they increased IK.Ca. When EGTA in the pipette solution
      was increased from 0.15 to 10 mM, the induction of IK.Ca by ACh and His was
      abolished. Thus, both ACh and His activate IK.Ca by increasing [Ca2+]i in JR-1
      cells. In the Ca(2+)-free bathing solution (0.15 mM EGTA in the pipette), ACh
      evoked IK.Ca transiently. Addition of Ca2+ (1.8 mM) to the bath immediately
      restored the sustained IK.Ca. These results suggest that the ACh response is due
      to at least two different mechanisms; i.e., the Ca2+ release-related initial
      transient activation and the Ca2+ influx-related sustained activation of IK.Ca.
      Probably because of desensitization, the Ca2+ influx-related component of the His
      response could not be identified. Intracellularly applied inositol 1,4,5
      trisphosphate (IP3), with and without inositol 1,3,4,5-tetrakisphosphate (IP4),
      mimicked the ACh response. IP4 alone did not affect the membrane current. Under
      the steady effect of IP3 or IP3 plus IP4, neither ACh nor His further evoked
      IK.Ca. Intracellular application of heparin or of the monoclonal antibody against
      the IP3 receptor, mAb18A10, inhibited the ACh and His responses in a
      concentration-dependent fashion. Neomycin, a phospholipase C (PLC) inhibitor,
      also inhibited the agonist-induced response in a concentration-dependent fashion.
      Although neither pertussis toxin (PTX) nor N-ethylmaleimide affected the ACh or
      His activation of IK,Ca, GDP beta S attenuated and GTP gamma S enhanced the
      agonist response.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8270910
TI  - Block of cardiac ATP-sensitive K+ channels by external divalent cations is
      modulated by intracellular ATP. Evidence for allosteric regulation of the channel
      protein.
AB  - We have investigated the interactions between extracellular divalent cations and
      the ATP-sensitive potassium channel in single guinea pig ventricular cells and
      found that, under whole-cell patch clamp recording conditions, extracellularly
      applied Co2+, Cd2+, and Zn2+ block current through the ATP-sensitive K channel
      (IKATP). The respective Kd's for block of IKATP by Cd2+ and Zn2+ are 28 and 0.46
      microM. The Kd for Co2+ is > 200 microM. Extracellular Ca2+ and Mg2+ appear to
      have no effect at concentrations up to 1 and 2 mM, respectively. Block of IKATP
      by extracellular cations is not voltage dependent, and both onset and recovery
      from block occur within seconds. Single-channel experiments using the inside-out
      patch configuration show that internally applied Cd2+ and Zn2+ are not effective
      blockers of IKATP. Experiments in the outside-out patch configuration confirm
      that the divalent cations interact directly with IKATP channel activity. Our
      study also shows that this block of IKATP is dependent on intracellular ATP
      concentrations. Under whole-cell conditions, when cells are dialyzed with
      [ATP]pipette = 0, the degree of cation block is reduced. This dependence on
      intracellular ATP was confirmed at the single-channel level by experiments in
      excised, inside-out patch configurations. Our results show that some, but not
      all, divalent cations inhibit current through IKATP channels by binding to sites
      that are not within the transmembrane electric field, but are on the
      extracellular membrane surface. The interdependence of internal ATP and external
      divalent cation binding is consistent with an allosteric interaction between two
      binding sites and is highly suggestive of a modulatory mechanism involving
      conformational change of the channel protein.

PMID- 8270911
TI  - A pH-sensitive and voltage-dependent proton conductance in the plasma membrane of
      macrophages.
AB  - Phagocytes generate large amounts of metabolic acid during activation. Therefore,
      the presence of a conductive pathway capable of H+ extrusion has been suggested
      (Henderson, L. M., J. B. Chappell, and O. T. G. Jones. 1987. Biochemical Journal.
      246:325-329). In this report, electrophysiological and fluorimetric methods were
      used to probe the existence of a H+ conductance in murine peritoneal macrophages.
      In suspended cells, recovery of the cytosolic pH (pHi) from an acid-load in Na+
      and HCO3(-)-free medium was detectable in depolarizing but not in hyperpolarizing
      media. The rate of alkalinization was potentiated by the rheogenic ionophore
      valinomycin. These findings are consistent with the existence of a conductive H+
      (equivalent) pathway. This notion was confirmed by patch-clamping and
      fluorescence ratio measurements of single adherent cells. When voltage was
      clamped in the whole-cell configuration, depolarizing pulses induced a sizable
      outward current which was accompanied by cytosolic alkalinization. Several lines
      of evidence indicate that H+ (equivalents) carry this current: (a) the
      conductance was unaffected by substitution of the major ionic constituents of the
      intra-and/or extracellular media, (b) the reversal potential of the tail currents
      approached the H+ equilibrium potential; and (c) the voltage-induced currents and
      pHi changes were both Zn2+ sensitive and had similar time course and potential
      dependence. The peak whole-cell current displayed marked outward rectification
      and was exquisitely H+ selective. At constant voltage, the H+ permeability was
      increased by lowering pHi but was inhibited by extracellular acidification.
      Together with the voltage dependence of the conductance, these features ensure
      that H+ extrusion can occur during activation, while potentially deleterious acid
      uptake is precluded. The properties of the conductance appear ideally suited for
      pHi regulation during phagocyte activation, because these cells undergo a
      sustained depolarization and an incipient acidification when stimulated.
      Comparison of the magnitude of the current with the amount of metabolic acid
      generated during macrophage activation indicates that the conductance is
      sufficiently large to contribute to the H+ extrusion required for maintenance of
      pHi.

PMID- 8270912
TI  - Whole-cell currents in single and confluent M-1 mouse cortical collecting duct
      cells.
AB  - M-1 cells, derived from a microdissected cortical collecting duct of a transgenic
      mouse, grown to confluence on a permeable support, develop a lumen-negative
      amiloride-sensitive transepithelial potential, reabsorb sodium, and secrete
      potassium. Electron micrographs show morphological features typical of principal
      cells in vivo. Using the patch clamp technique distinct differences are detected
      in whole-cell membrane current and voltage (Vm) between single M-1 cells 24 h
      after seeding vs cells grown to confluence. (a) Under control conditions
      (pipette: KCl-Ringer; bath: NaCl-Ringer) Vm averages -42.7 +/- 3.4 mV in single
      cells vs -16.8 +/- 4.1 mV in confluent cells. Whole-cell conductance (Gcell) in
      confluent cells is 2.6 times higher than in single cells. Cell capacitance values
      are not significantly different in single vs confluent M-1 cells, arguing against
      electrical coupling of confluent M-1 cells. (b) In confluent cells, 10(-4)-10(-5)
      M amiloride hyperpolarizes Vm to -39.7 +/- 3.0 mV and the amiloride-sensitive
      fractional conductance of 0.31 shows a sodium to potassium selectivity ratio of
      approximately 15. In contrast, single cells express no significant amiloride
      sensitive conductance. (c) In single M-1 cells, Gcell is dominated by an inwardly
      rectifying K-conductance, as exposure to high bath K causes a large
      depolarization and doubling of Gcell. The barium-sensitive fraction of Gcell in
      symmetrical KCl-Ringer is 0.49 and voltage dependent. (d) In contrast, neither
      high K nor barium in the apical bath affect confluent M-1 cells, showing that
      confluent cells lack a significant apical K conductance. (e) Application of 500
      microM glibenclamide reduces whole-cell currents in both single and confluent M-1
      cells with a glibenclamide-sensitive fractional conductance of 0.71 and 0.83 in
      single and confluent cells, respectively. Glibenclamide inhibition occurs slower
      in confluent M-1 cells than in single cells, suggesting a basolateral action of
      this lipophilic drug on ATP-sensitive basolateral K channels in M-1 cells. (f) A
      component of the whole-cell conductance in M-1 cells appears as a deactivating
      outward current during large depolarizing voltage pulses and is abolished by
      extracellular chloride removal. The deactivating chloride current averages 103.6
      +/- 16.1 pA/cell, comprises 24% of the outward current, and decays with a time
      constant of 179 +/- 13 ms. The outward to inward conductance ratio obtained from
      deactivating currents and tail currents is 2.4, indicating an outwardly
      rectifying chloride conductance.

PMID- 8270913
TI  - Spinal cord injury and aging: exploring the unknown. 1993 Heiner Sell Lecture of
      the American Spinal Injury Association.

PMID- 8270914
TI  - Pharmacology of locomotion: an account of studies in spinal cats and spinal cord
      injured subjects.
AB  - This paper summarizes a research approach which started with experiments in cats
      and eventually led to the successful use of drugs in spinal cord injured (SCI)
      patients to improve their walking. In such a short paper, it is impossible to
      cover the details of this approach but we will establish important landmarks and
      give a bibliography to guide further reading.

PMID- 8270915
TI  - Spirometry--acceptability and reproducibility in spinal cord injured subjects.
AB  - The American Thoracic Society (ATS) has formulated guidelines for spirometry. We
      hypothesized that individuals with SCI (SCI), as a result of weak respiratory
      muscles, would exhibit poor test acceptability and reproducibility. Seventy-eight
      SCI subjects (39 with complete SCI) answered a respiratory questionnaire and
      performed spirometry. Of those with complete SCI, the proportion of subjects
      which met ATS criteria decreased with higher levels of injury. Poor test
      performance was not associated with age, respiratory symptoms or muscle fatigue.
      The most common reason for failing to meet ATS criteria for acceptability was
      excessive back extrapolated volumes (EBEV). Individuals with efforts that were
      acceptable except for EBEV and/or for exhalation of less than six seconds had
      values for forced expiratory volume in one second (FEV1) and forced vital
      capacity (FVC) that were reproducible. If ATS criteria for acceptable spirometry
      were used in studying subjects with SCI, individuals producing otherwise
      reproducible values for FVC and FEV1 would be excluded. We found reproducibility
      similar to what has been reported in other cohorts and conclude that longitudinal
      study of respiratory function in SCI is feasible.

PMID- 8270916
TI  - Penoplasty for receding phallus: a new surgical technique to prevent dislodging
      of external urinary collecting device.

PMID- 8270917
TI  - Effectiveness of the use of humor in the rehabilitation of people with SCI: a
      pilot study.
AB  - Despite the empirically established beneficial effects of laughter on
      psychological health, humor remains a much neglected area of research. This study
      examined the psychological impact of humor on people with SCI, the hypothesis
      being that it would significantly reduce the deleterious psychological effects of
      the injury. Mood state, frequency of intrusive thoughts and avoidance behavior of
      eight male inpatients at the National Spinal Injuries Centre were monitored
      before and after exposure to a series of five humorous video presentations.
      Although differences in these parameters were in the predicted direction,
      statistical analysis revealed no significant effect. Nevertheless, this pilot
      study highlighted pertinent issues and suggested modifications for further
      exploration.

PMID- 8270918
TI  - Progression from asymptomatic to symptomatic urinary tract infection in patients
      with SCI: a preliminary study.
AB  - The purpose of this prospective pilot study was to (1) evaluate the role of
      pyuria in predicting the progression from asymptomatic to symptomatic urinary
      tract infection (UTI) in spinal cord-injured patients who undergo sterile
      intermittent bladder catheterization and (2) evaluate the impact of treating
      asymptomatic UTI on this progression. Twenty hospitalized patients were
      randomized to either the treatment group (10 subjects) or the control group (10
      subjects). Weekly urine samples were obtained for quantitation of bacterial
      growth and pyuria. Neither the level nor the trend of pyuria helped predict the
      imminent progression to symptomatic UTI. Thirty percent of patients in the
      treatment group developed symptomatic UTI vs 70 percent of patients in the
      control group; it took a significantly longer time for patients in the treatment
      vs control group to develop symptomatic UTI (median number of days: 72 vs 7,
      respectively; p < 0.003). Further analysis of the long-term impact of antibiotic
      treatment of asymptomatic UTI is warranted.

PMID- 8270919
TI  - The motor disorder of multiple system atrophy.

PMID- 8270920
TI  - Anders Celsius (1701-1744).

PMID- 8270922
TI  - Effect of age on treatment decisions in low-grade glioma.
AB  - The proper treatment of low-grade glioma is unclear and major uncertainties
      include the timing of therapy, the need for extensive surgery, or the application
      of radiotherapy. Although prospective trials are in progress, it may be years
      before results become available, as the five-year survival of low-grade glioma is
      around 45% or more. Age is an important prognostic factor in malignant glioma,
      but its implications for decisions on treatment have not yet been addressed in
      guidelines. This review examines the interaction between age and the results of
      applied treatment, based on data from published series. The available evidence
      suggests that, in younger patients, whether treatment is started early or late
      does not seem to affect long-term survival substantially. For patients under 35
      years of age, more radical surgery appears to be beneficial, while radiation does
      not seem to improve the outcome. For patients who are 35 years and older, surgery
      and radiotherapy seems to produce better survival rates. The age of the patients
      should therefore be considered when decisions on the treatment of supratentorial,
      non-pilocytic, low-grade gliomas. For patients under 35 years of age who have
      either epilepsy or a surgically inaccessible tumour, it is advisable to defer
      treatment. The tumour should be largely excised, if possible. Following any
      surgery, radiotherapy should be withheld in this age group. For patients over 35
      years of age, early treatment, including biopsy or surgery followed by
      radiotherapy, should not be delayed. Because of more prolonged survival, and to
      prevent neurotoxicity, radiation fields should be limited to the tumour bed and
      not include the whole of the brain. Future trials need to establish whether age
      is a crucial factor in deciding the timing and extent of treatment in patients
      with low-grade glioma.

PMID- 8270923
TI  - Pathogenetic and prognostic features of lacunar transient ischaemic attack
      syndromes.
AB  - Lacunar ischaemic stroke syndromes are a well defined subgroup of ischaemic
      strokes. To determine whether a similar subgroup can be identified among patients
      with transient ischaemic attacks (TIAs) we studied prospectively 102 consecutive
      patients within 24 hours of their first TIA. Based on their history they were
      classified as lacunar TIA syndromes (LTIAS; n = 45) if isolated motor or sensory
      symptoms or their combination had involved at least two of three body parts
      (face, arm, leg), whereas all other subjects were grouped as non-lacunar TIA
      syndromes (NLTIAS; n = 57). All patients were investigated according to a
      standardised protocol and followed up for an average of 51.1 months. Cardiac and
      arterial sources of thromboembolism were more frequent among NLTIAS (p = 0.0001).
      Survival curve analysis demonstrated that LTIAS had a significantly lower long
      term mortality and incidence of major vascular events. In a multivariate
      regression analysis, the type of TIA (that is, NLTIAS) was an independent
      predictor of stroke or death. LTIAS share the same distinct pathogenetic and
      prognostic features of lacunar ischaemic stroke syndromes. These findings have
      implications for management of TIAs and for studies of their natural history and
      treatment.

PMID- 8270921
TI  - Management of cerebral infection.

PMID- 8270924
TI  - The first description of idiopathic progressive bulbar palsy.

PMID- 8270925
TI  - Effect of vigabatrin on sedation and cognitive function in patients with
      refractory epilepsy.
AB  - Twenty-four patients with refractory epilepsy on one or more antiepileptic drugs
      were given additional vigabatrin (1 g twice daily for six weeks, followed by 1.5
      g twice daily for a further six weeks) and matched placebo in a double blind,
      randomised, crossover study. A battery of neuropsychological tests was
      administered at baseline and at weeks two, six and 12 of both treatment periods.
      No significant differences were found between vigabatrin and placebo at any time
      point for any of the objective tests of cognitive function. Patients, however,
      reported a greater degree of sedation after two and six weeks on vigabatrin than
      during the equivalent placebo phase (p < 0.01), although no such difference was
      apparent at 12 weeks. Follow up over a mean of 14.75 months in 12 responders, who
      continued on vigabatrin, revealed a significant improvement (all p < 0.01) on
      each of three composite scales (three psychomotor tests, four memory tests, three
      self rating scales) compared with their scores during the double blind trial.
      Vigabatrin did not cause cognitive impairment either acutely or in the long term.
      Phased introduction, however, seems a prudent policy to allow tolerance to early
      subjective sedation.

PMID- 8270926
TI  - Historical description of primary writer's tremor.

PMID- 8270927
TI  - Influence of sensory manipulation on postural control in Parkinson's disease.
AB  - Postural control was assessed on a tilting platform system in 20 patients with
      idiopathic Parkinson's disease and 20 age-matched controls. The amount of
      information provided by vision and lower limb proprioception was varied during
      the experiment to investigate the influence of changes in sensory cues on
      postural control. The patient group with clinical evidence of impaired postural
      control (Hoehn and Yahr III) had significantly higher sway scores over all
      sensory conditions than either the Hoehn and Yahr II group or controls. The
      pattern of sway scores indicated that no obvious deficit in the quality, or
      processing, of sensory information was responsible for the postural instability
      observed in this group. The patients in both Hoehn and Yahr groups were also able
      to respond appropriately to potentially destabilising sensory conflict situations
      and significantly improved their sway scores when provided with visual feedback
      of body sway. The results indicate that in Parkinson's disease, the main site of
      dysfunction in postural control is likely to be at a central motor level.

PMID- 8270928
TI  - Cholinergic treatment of an amnestic man with a basal forebrain lesion:
      theoretical implications.
AB  - Cholinergic deficient states, such as in Alzheimer's disease, are associated with
      amnesia. Therapeutic trials with cholinergic augmentation in Alzheimer's disease
      have had only equivocal results, but mechanisms other than cholinergic deficiency
      may contribute to the memory deficit. Normally the diagonal band of Broca
      provides much of the hippocampal cholinergic input. To learn if amnesia secondary
      to cholinergic deficiency can be ameliorated by cholinergic augmentation, we
      treated an amnestic man who had a lesion located primarily in the right diagonal
      band of Broca with physostigmine and lecithin. During the initial best-dose
      finding phase, he demonstrated an inverted U-shaped curve for immediate recall of
      word lists, with peak performances at 3.0 and 3.5 mg of physostigmine. Single
      photon emission tomography showed decreased blood flow in the medial temporal
      region ipsilateral to the lesion at baseline, with a reversal of the asymmetry on
      3.5 mg of physostigmine. A follow-up double-blind, placebo-controlled study on
      3.5 mg of physostigmine, however, failed to demonstrate that cholinergic
      treatment improved memory.

PMID- 8270929
TI  - Dorsolateral prefrontal cortex dysfunction in the major psychoses; symptom or
      disease specificity?
AB  - Neurophysiological deficits in the left dorsolateral prefrontal cortex (DLPFC)
      have been described in positron emission tomography studies of schizophrenia and
      depression. In schizophrenia and depression this deficit has been associated with
      the syndromes of psychomotor poverty and psychomotor retardation, respectively.
      Such findings lead to a prediction that DLPFC dysfunction is symptom rather than
      disease related. This prediction was empirically tested in a retrospective study
      that pooled data from 40 patients meeting research diagnostic criteria for
      depression and 30 patients meeting DSM-III R criteria for schizophrenia. The
      patients were categorised into those with and without poverty of speech, a
      symptom that is an observable manifestation of psychomotor impairment. The
      profile of regional cerebral blood flow (rCBF), measured in all subjects under
      resting conditions, was subsequently compared in these two groups. Patients with
      poverty of speech had significantly lower rCBF in the left DLFPC. This reduction
      of rCBF was independent of diagnosis. The findings support the view that the
      study of symptoms, or symptom clusters, can provide information additional to
      that of traditional diagnostic systems in the study of the major psychoses.

PMID- 8270930
TI  - Investigation of the opioid system in absence seizures with positron emission
      tomography.
AB  - The neuroanatomical and pathophysiological basis of primary generalised absences
      is uncertain. Administration of endogenous opioids has been shown to result in
      absence-like seizures in animal models. Positron emission tomography scans were
      performed in eight patients with primary generalised epilepsy and eight control
      subjects. Regional cerebral blood flow was measured interictally with C15O2,
      after which a 90 minute dynamic study with the opioid-receptor ligand 11C
      diprenorphine was performed. Serial absences were precipitated by
      hyperventilation for 10 minutes, starting 30-40 minutes after injection of
      diprenorphine. Absences, with generalised spike-wave discharges on the EEG,
      occurred for between 10% and 51% of the provocation period. No individual (normal
      or patient) had any interictal focal abnormalities of cerebral blood flow. After
      provocation of serial absence seizures, there was increased diprenorphine
      elimination from the association cortex, but not from the thalamus, basal
      ganglia, or cerebellum, compared with control subjects and patients scanned
      without provocation of absences. It was possible to simulate the observed
      increased diprenorphine elimination following seizures in cerebral cortex using a
      two tissue compartment model, with an estimated 15-41% decrease in the specific
      tracer uptake rate constant (k3). These results suggest that endogenous opioids
      are released in the association cortex at the time of serial absences, lead to
      increased receptor occupancy, and may have an important role in the
      pathophysiology of generalised absences.

PMID- 8270931
TI  - Early descriptions of sleep paralysis.

PMID- 8270932
TI  - Spectral analyses of activity of laryngeal and orofacial muscles in stutterers.
AB  - Previous studies have reported that the disfluent speech of stutterers is often
      associated with tremor in orofacial muscle systems. In the present report,
      spectral analyses of the amplitude envelopes of laryngeal and orofacial EMGs
      revealed that tremor-like oscillations of EMG activity, similar to those observed
      in orofacial muscles, are also present in laryngeal muscles during stuttered
      speech. Furthermore, tremor-like oscillations in orofacial and laryngeal muscles
      appear to be entrained in some subjects. It is speculated that autonomic systems
      may provide a mechanism whereby oscillations in different muscle groups may
      become entrained.

PMID- 8270933
TI  - Samuel Johnson: victim of Gilles de la Tourette syndrome.

PMID- 8270934
TI  - Eyelid myoclonia with typical absences: an epilepsy syndrome.
AB  - Five unrelated patients are described with the clinical and electrical features
      of eyelid myoclonia with absences (EMA). In this syndrome brief, typical absences
      occur with rapid eyelid myoclonia associated with retropulsive movements of the
      eyeballs and occasionally of the head. The seizures are of shorter duration than
      in childhood absence epilepsy, and are accompanied by less profound impairment of
      consciousness. The electroencephalogram demonstrates high amplitude discharges
      consisting of spikes, multiple spikes and slow waves at a fluctuating frequency
      of 3-5 Hz and following eye closure, which disappear in darkness.
      Photosensitivity is also seen. Onset is in early childhood and EMA appears to
      persist into adult life. Treatment is sodium valproate in combination with either
      ethosuximide or a benzodiazepine. On the basis of the clinical features, EEG
      findings, and the response to treatment and prognosis, it is suggested that EMA
      be classified as a specific epilepsy syndrome.

PMID- 8270935
TI  - Seizures due to multiple sclerosis: seven patients with MRI correlations.
AB  - The MRI data of seven patients with clinically definite multiple sclerosis who
      developed epileptic seizures are presented. Six of these cases demonstrated new
      or enhancing lesions. Cerebral biopsy in one of these lesions confirmed
      inflammation with myelin breakdown products. Lesions implicated in the causation
      of seizures involved the cortex or subcortical area. In one patient, a new lesion
      was associated with EEG abnormalities which resolved as the lesion reduced in
      size. In three patients epileptic activity was the only clinical manifestation of
      disease. Large, unresolving lesions tended to be associated with continuing
      seizures.

PMID- 8270936
TI  - A case of "voluntary nystagmus" and head tremor.
AB  - A 24-year-old woman presented with nystagmus and head tremor. Both were transient
      and could be executed simultaneously at different frequencies of oscillation. It
      is unusual for these two movements, which can be voluntary, to occur together.
      Suspicions of an acquired disease were not confirmed on further investigation
      using DC-coupled electro-oculography and angular accelerometry, and on an
      admission by the patient that the nystagmus could be voluntary. Voluntary
      nystagmus can become semi-automatic and a patient may be able to simulate more
      than one "involuntary movement" simultaneously yet at different frequencies.

PMID- 8270937
TI  - Primitive reflexes in Parkinson's disease.
AB  - A standardised protocol for the examination of 15 primitive reflexes in which the
      amplitude and the persistence were scored separately, was applied to 25 patients
      with Parkinson's disease and an equal number of healthy matched control subjects.
      Most reflexes were found considerably more often in the patients than in the
      control subjects, especially the snout, the glabellar tap, and its variant, the
      nasopalpebral reflex. Only the mouth open finger spread reflex was present more
      often in the control subjects. For all reflexes except this last, the scores for
      amplitude and persistence of the reflexes for the control group never exceeded
      the scores for the patient group. Reflexes persisted more often in the patients
      than in the control subjects. Parkinsonism alone can explain a large number of
      primitive reflexes, irrespective of the severity or duration of the disease. In
      contrast, the number of reflexes was related more closely to cognitive scales. It
      is concluded that such reflexes may be helpful in diagnosing Parkinson's disease.
      In addition, a standardised protocol for eliciting and scoring is essential for
      the study of these reflexes in parkinsonism and other neuropsychiatric
      conditions.

PMID- 8270938
TI  - Abnormal cerebral blood flow following transient global amnesia.

PMID- 8270939
TI  - Malaria myositis.

PMID- 8270940
TI  - Subtle cerebral lesions in "chronic whiplash syndrome"?

PMID- 8270941
TI  - "Familial paroxysmal tremor": an essential tremor variant?

PMID- 8270942
TI  - Car toll neuropathy.

PMID- 8270943
TI  - Early diagnosis and intravenous immune globulin therapy in paraneoplastic
      cerebellar degeneration.

PMID- 8270944
TI  - Neuroradiological anomalies and schizophrenia.

PMID- 8270945
TI  - Delirium and quantitative EEG.

PMID- 8270946
TI  - Diagnosis by axilla skin biopsy in an early case of Lafora's disease.

PMID- 8270947
TI  - Devic's neuromyelitis optica and Schilder's myelinoclastic diffuse sclerosis.

PMID- 8270948
TI  - Localization of subrhabdomeric haemolymph lacunae in the retina of Drosophila
      melanogaster and Calliphora erythrocephala.
AB  - The haemolymph of flies and other insects contains tyrosinase (EC 1.14.18.1), the
      rate-limiting enzyme in mammalian melanogenesis. After incubation with 5 mM L
      DOPA for several hours the endogenous tyrosinase of the haemolymph forms an
      electron dense reaction product. This method was used to localize spaces in the
      retina of the wild type and the white (w) mutant of Drosophila melanogaster that
      are filled with haemolymph. A network of subrhabdomeric haemolymph lacunae was
      found. Moreover it was found that these haemolymph lacunae also form extensions
      into the photoreceptor cells and are connected with small haemolymph lacunae that
      cross the retinal basement membrane. In a second set of experiments L-DOPA was
      injected into the thoraces of Calliphora erythrocephala. Half-an-hour after
      injections the flies were killed and the eyes were embedded for electron
      microscopy. The small molecule of DOPA or its product dopachrome, surprisingly,
      penetrated the retinal basement membrane and reached the subrhabdomeric
      haemolymph lacunae and the ommatidial cavity.

PMID- 8270949
TI  - Cyclic 3',5'-nucleotide phosphodiesterase: cytochemical localization in
      photoreceptor cells of the fly Calliphora erythrocephala.
AB  - The distribution of cyclic 3',5'-nucleotide phosphodiesterase activity was
      determined in photoreceptor cells of the fly Calliphora erythrocephala. With cAMP
      as substrate, staining was most intense within the phototransducing region of
      these cells, the rhabdomeral microvilli and also in the extracellular space
      surrounding the microvilli and in the mitochondria. With cGMP as substrate, the
      intensity within the rhabdomeres was less marked, while their extracellular
      surroundings were stained heavily. Thus, compared to cGMP, cAMP is the better
      substrate for the phosphodiesterase in the rhabdomeres of the fly. For
      comparison, the same cytochemical method was used to localize the well-known
      phosphodiesterase activity in retinal tissue of the mouse. Under the same
      conditions as used for fly photoreceptors, a very intense reaction product was
      obtained in rod outer segments. With regard to the conflicting reports concerning
      the light-stimulated changes of cyclic nucleotides in invertebrate photoreceptor
      cells, the results presented here further argue for an important role of a cyclic
      nucleotide in the process of phototransduction of invertebrates.

PMID- 8270950
TI  - Freeze fracture analysis of apical membranes in cochlear cultures: differences
      between basal and apical-coil outer hair cells and effects of neomycin.
AB  - Previous studies have shown that exposure of cochlear cultures to the ototoxic
      aminoglycoside antibiotic neomycin leads to the rapid formation of numerous
      membrane filled protrusions on the apical surface of the hair cells but not on
      the surrounding supporting cells, and that hair cells in basal-coil cultures are
      more sensitive to these effects of neomycin than those in the distal end of
      apical-coil cultures. Freeze-fracture has been used to examine and compare the
      apical surfaces of hair cells and supporting cells in basal and apical-coil
      cultures in order to look for features that may explain the differential
      sensitivity of the various cell types to neomycin, and to characterize the
      membrane type that forms in response to neomycin and compare it with the normal
      apical membrane of the hair cell. The apical surface of the highly responsive
      basal-coil outer hair cells differs significantly from the apical surfaces of
      apical-coil outer hair cells and supporting cells in both regions of the cochlea
      in both surface area and the number and density of endocytotic vesicles
      associated with this surface. Basal-coil hair cells have an average of 120 +/- 39
      vesicles per cell surface and a density of 3.5 +/- 0.89 vesicles per microns 2,
      whereas apical-coil hair cells have 14.8 +/- 15.8 vesicles/cell surface and
      density of 0.73 +/- 0.72 vesicles per microns 2. There are no significant
      differences in intramembrane particle (IMP) density on the apical surfaces of all
      the cell types examined, and qualitative observations of filipin-treated
      specimens indicate that cholesterol densities are also similar. The membrane that
      accumulates in response to neomycin treatment at the apical pole of the hair cell
      is IMP free, does not respond to filipin, and fractures in a manner that is
      indicative of a high content of unsaturated phospholipid in a fluid phase, and is
      therefore different in several respects from the normal apical surface of the
      hair cell. The results of this study suggest that apical surface associated
      endocytotic vesicle numbers may determine the differential sensitivity of apical
      and basal-coil hair cells to neomycin, and that neomycin may interfere with some
      aspect of phospholipid metabolism or membrane turnover in sensory hair cells.

PMID- 8270952
TI  - A special issue in honour of George Gray.

PMID- 8270951
TI  - Monoclonal antibody Cat-301 selectively identifies a subset of nuclei in the
      cat's somatosensory thalamus.
AB  - Recently it has been demonstrated that the monoclonal antibody Cat-301 is capable
      of identifying functionally related neurons in the mammalian visual thalamus. We
      have examined the possibility that this antibody might display a similar capacity
      in nonvisual thalamic areas. We demonstrate that in the cat's somatosensory
      thalamus the distribution of Cat-301-positive cells and neuropil is restricted to
      a subset of nuclei. These include the ventroposterior medial, ventroposterior
      lateral, and ventroposterior inferior nuclei. Staining with Cat-301 provides a
      clear visualisation of the entire somatotopic map within these nuclei. The
      somatosensory sector of the thalamic reticular nucleus and the perireticular
      nucleus, which may have a somatosensory sector, are also Cat-301-positive. In
      contrast, cells that do not express the Cat-301 antigen are located in the
      ventroposterior oralis nucleus, the ventroposterior shell region, the medial and
      lateral divisions of the posterior nuclear group, and the inner small cell region
      adjacent to the thalamic reticular nucleus. In comparison with previous
      physiological studies, cells that express the Cat-301 antigen most likely
      represent subpopulations in only a few of the somatic submodality-specific
      groups. These include cells in the small-field and Pacinian cutaneous-responsive
      groups, excluding cells in the wide-field cutaneous-, muscle-, joint-, and
      noxious-responsive groups. Taken together these findings indicate that monoclonal
      antibody Cat-301 is capable of selectively identifying neurons with distinct
      functional properties in the mammalian somatosensory thalamus.

PMID- 8270953
TI  - George Gray.

PMID- 8270954
TI  - Ultrastructural evidence of sexual dimorphism in supraoptic neurons: a
      morphometric study.
AB  - We have recently shown that in spite of the absence of receptors for gonadal
      steroids in the supraoptic nucleus (SON) of the rat hypothalamus, the volume of
      the nucleus and the size of its neurons are larger in males than in females, and
      that these differences between male and female rats are correlated with body
      weight and dependent on the vasopressinergic neurons. As supraoptic neurons and
      their organelles enlarge when they are engaged in active peptidergic secretion we
      have carried out a morphometric ultrastructural analysis to determine if cell
      structures involved in the synthesis and storage of neurosecretory material also
      display weight-dependent sex dimorphism. Groups of six male and six female rats
      aged 30, 60 and 180 days were used. Nucleoli, rough endoplasmic reticulum and
      neurosecretory granules were analysed and we estimated their volume or surface
      densities and the total volume of nucleoli and rough endoplasmic reticulum, and
      total surface area of rough endoplasmic reticulum. We found that, with the
      exception of neurosecretory granules, the densities of the organelles did not
      differ among the groups studied, but total values were higher in males. These
      differences were found to be weight-dependent. Since the organelles studied are
      regarded as reliable indicators of the neurosecretory activity of supraoptic
      neurons, our data fully support the view that the weight-dependent sexual
      dimorphism observed in this nucleus reflects greater synthetic activity of its
      vasopressinergic neurons associated with the need to maintain water balance in
      larger bodies.

PMID- 8270955
TI  - Different rates of axonal degeneration in the crossed and uncrossed retinofugal
      pathways of Monodelphis domestica.
AB  - The uncrossed retinofugal fibres in the marsupial Monodelphis domestica form a
      separate bundle as they pass through the optic chiasm. The uncrossed fibres
      segregate from the crossed fibres a short distance before they reach the chiasm,
      gathering as an essentially exclusive bundle in the ventral part of the optic
      nerve. This bundle then passes laterally through the optic chiasm and into the
      optic tract. The distinctive position of the uncrossed fibres has allowed us to
      recognise that, surprisingly, the uncrossed fibres degenerate more rapidly than
      the rest. Seven days after a monocular enucleation approximately 60-80% of the
      fibres of the crossed component in the main part of the optic nerve near the
      chiasm have a normal cross sectional appearance in electron micrographs whereas
      less than 20% of the fibres in the uncrossed bundle look normal. The rapid
      degeneration of the uncrossed fibres cannot be related to any morphological
      parameter of the axons. Their fibre diameters are mainly medium to thick, lying
      within the range of axon diameters found in the rest of the nerve. The axon
      myelin ratios of the uncrossed fibres are also no different from those of the
      crossed optic fibres. There are no structural peculiarities identifiable with
      light or electron microscopical methods in either the axons or in the glia of the
      uncrossed bundle that might account for the more rapid degeneration. There is
      evidence that the degenerative change in the main part of the optic nerve
      progresses from the lesion towards the chiasm, and that for the crossed fibres it
      may progress slightly faster for the thicker than for the thinner fibres. The
      degeneration in the uncrossed bundle does not fit any of the rules that have been
      proposed for relating rate of degeneration to fibre diameter. We conclude that
      the rate of Wallerian degeneration is determined by factors that yet remain to be
      defined.

PMID- 8270956
TI  - Organization of microtubules in axonal growth cones: a role for microtubule
      associated protein MAP 1B.
AB  - Neuronal growth cones guide growing axons and dendrites (neurites) through
      developing embryos by detecting extrinsic guidance cues and transducing the
      signal into changes in motile behaviour. In this brief review, the role of the
      growth cone cytoskeleton in these events, in particular the microtubules, is
      discussed. Microtubules in the neurite are mainly bundled into fascicles whereas
      on entering the growth cone they diverge from each other and traverse the central
      (C)-domain of the growth cone. Occasionally, individual microtubules extend as
      far as the peripheral (P)-domain and may even enter filopodia. Microtubules in
      the growth cone are probably dynamically unstable, exchanging dimer with a large
      pool of soluble tubulin. It is proposed that the 'capture' of dynamically
      unstable microtubules by filopodial actin filament bundles is a crucial step
      underlying directed growth. Localised assembly of microtubules at the growth
      cone, rather than at the cell body followed by transport of polymer to the growth
      cone, may facilitate the delivery of material to specific regions of the growth
      cone and hence allow vectorial growth. Bundling of microtubules and capture of
      microtubules by filopodia both imply roles for microtubule-associated proteins
      (MAPs). Several microtubule-associated proteins are present within growth cones,
      including MAP 1B, MAP2 and tau. Recent experiments point toward a phosphorylated
      form of MAP 1B as an important component in neurite elongation and in particular
      in the bundling of microtubules in the growth cone.

PMID- 8270957
TI  - Microtubule-associated protein 2 and the organization of cellular microtubules.
AB  - Microtubule-associated proteins (MAPs) are prominent components of the neuronal
      cytoskeleton that can promote microtubule formation and whose expression is under
      strong developmental regulation. They are thought to be involved in organizing
      the structure of microtubule fascicles in axons and dendrites, although whether
      they form active cross-links between microtubules or serve as strut-like spacer
      elements has yet to be resolved. In the experiments reported here we explored
      their influence on microtubules by expressing them in non-neuronal cells using
      DNA transfection techniques. We confirm earlier reports that microtubule
      associated proteins of the MAP2/tau class can induce bundling of microtubules. In
      addition we find that MAP2 causes the rearrangement of microtubules in the
      cytoplasm in a manner that is dependent on the length of the microtubule bundles.
      Short bundles are straight and run across the cytoplasm whereas long bundles form
      a marginal band-like array at the periphery. We suggest that the latter
      arrangement is produced when microtubule bundles that are too long to fit inside
      the diameter of the cell bend under the restraining influence of the cortical
      cytoskeleton. In confirmation of this, we show that when the cortical actin
      network is depolymerized by cytochalasin B the MAP2-containing microtubule
      bundles push out cylindrical extensions from the cell surface. These results
      suggest that the induction of stiff microtubules bundles by MAP2, coupled with a
      breach in the cortical actin network, can confer two of the properties
      characteristic of neuronal processes; their cylindrical form and the presence of
      fasciculated microtubules.

PMID- 8270958
TI  - Rapid recovery of structure and function of the cholinergic synapses in the cat
      superior cervical ganglion in vivo following stimulation-induced exhaustion.
AB  - Cat superior cervical ganglia (SCG) were tetanically stimulated in vivo at 30-100
      Hz until neural transmission was exhausted, and then were allowed to rest and
      recover. Changes in their cholinergic synapses were examined
      electrophysiologically and morphologically during the time of tetanic stimulation
      and during recovery. For morphometric analysis the presynaptic terminal was
      subdivided into two areas: an area directly over the active zone, termed zone-I,
      (bounded by a hemicircle with a diameter equivalent to the active zone length),
      and the remaining preterminal area, termed zone-II. In control ganglia before
      stimulation synaptic vesicle density in zone-I (SVD-I) averaged 90 microns-2 and
      the number of vesicles actually attached to the active zone (SVA) averaged about
      2.5 per single profile of nerve terminal. Upon stimulation, the postganglionic
      potential immediately began to decline in amplitude and disappeared after 1 min
      of stimulation. Simultaneously, SVD-I declined to less than 35 microns-2 and SVA
      declined to less than 1 per section. Thereafter, stimulation was terminated and
      the ganglion was allowed to rest. Recovery of the postganglionic potential was
      monitored by stimulation at 1 Hz. The postganglionic potential reached control
      levels after only 1 min of rest. Likewise, the structural parameters, SVD-I and
      SVA, also rapidly recovered, reaching control levels after only 30 sec of rest,
      slightly faster than the postganglionic potential. This illustrates that
      stimulation-induced fatigue of transmitter output and depletion of synaptic
      vesicles recover to the control level at a high rate in synapses of the cat SCG
      with a normal supply of blood. In fact, morphological recovery may be slightly
      faster than electrophysiological recovery. Mechanisms of vesicle formation and
      migration to the presynaptic area are discussed in light of these observations.

PMID- 8270959
TI  - Morphological characteristics of perforated synapses in the latter stages of
      synaptogenesis in rat neocortex: stereological and three-dimensional approaches.
AB  - Over recent years attention has been focused on perforated synapses (PSs), on
      account of their possible involvement in synaptic plasticity in the nervous
      system. The mechanism invoked has involved the conversion of conventional (non
      perforated) synapses into perforated ones, with the latter subsequently splitting
      to form new daughter synapses. Data challenging this mechanism have emerged from
      studies using unbiased stereological and three-dimensional reconstruction
      procedures in early synaptogenesis and also in early- to mid-adulthood. The
      present study is an attempt to complement these earlier studies by concentrating
      on the latter part of synaptogenesis and early adulthood in rats (7-60 days
      postnatal). Using the disector method, the frequency of perforated synapses
      increases with age from 12% at seven days to 33% at 60 days. Reconstruction of
      the perforated synapses has led to the description of three sub-types, while
      quantitation of the reconstructions has highlighted major differences between
      perforated and non-perforated synapses over this developmental period. For
      instance, the postsynaptic density of perforated synapses increases in size with
      age, but remains static in the non-perforated variety; in addition, it is 2-3
      times larger in perforated synapses. The proportion of the synaptic contact zone
      occupied by the postsynaptic density increases in perforated synapses with
      increasing age, but is static in non-perforated synapses. No evidence has been
      found to support a perforated synapse splitting model, since perforated synapses
      are present from early in synaptogenesis, the frequency of non-perforated
      synapses reaches a peak prior to, but not following, that of perforated synapses,
      and the size of the postsynaptic density of non-perforated synapses remains
      constant throughout the period of the study.

PMID- 8270960
TI  - Cone synapses of a flat diffuse cone bipolar cell in the primate retina.
AB  - A Golgi-stained flat diffuse cone bipolar cell from a vervet monkey's retina
      (Cercopithecus aethiops), contacting six cones, was serially sectioned for
      electron microscopy (EM) to determine the types of synapses it made with the cone
      pedicles. All the synapses were basal (flat) contacts. Their distribution and
      ultrastructural type were similar at each pedicle. Approximately half the
      synapses were definable as triad-associated and the rest were elsewhere on the
      cone pedicle base. Their ultrastructure is the same regardless of those
      positions. About 25 synapses were made with each cone. Thus this type (DB2 of
      Boycott & Wassle, 1991) of flat diffuse cone bipolar cell is in contact with six
      cones through about 150 synapses. At the eccentricity studied each cone pedicle
      probably makes 90-100 basal synapses with between three and four DB2 bipolar
      cells. This is between two and three times the number that are made with all the
      types of invaginating bipolar cells. A brief review of cone photoreceptor
      synapses with bipolar cells shows that, for those so far examined in the primate
      retina, the dichotomy into two types of bipolar cell invaginating (ribbon
      related), with axons ending in the b-layer of the inner plexiform layer (IPL)
      (hence presumptive On-bipolars) and flat (basal synapses), with axons ending in
      the a-layer of the inner plexiform layer (hence presumptive Off-bipolars) is the
      rule. But other vertebrate retinae, including that of the cat, also have bipolar
      cells which vary from this pattern.

PMID- 8270962
TI  - Axon hillocks and initial segments in spinal trigeminal nucleus with emphasis on
      synapses including axo-axo-axonic contacts.
AB  - As a part of a continuing study of the feline spinal trigeminal nucleus, the fine
      structure and synaptic arrangements on the axon hillock and axon initial segment
      of neurons in this region are described here. Transmission electron microscopy
      has been used to characterize qualitatively the axon hillock and initial segment
      and associated synapses in pars interpolaris. Axon hillocks and initial segments
      are easily identified in continuity with somata or as isolated profiles in the
      neuropil, and they receive synaptic contacts: these we regard as axo-axonic. The
      presynaptic terminals contain either mainly round or mainly flattened synaptic
      vesicles and have Type I (asymmetric) or Type II (symmetric) thickenings
      respectively at their contacts with the axon hillock or initial segment. I report
      here also the unusual arrangement of three separate axons in a serial synaptic
      complex. Some of the round vesicle Type I contacts onto the axon hillock-initial
      segment region also receive Type II contacts from one or more flattened vesicle
      terminals, thus forming an axo-axo-axonic complex. These flattened vesicle
      terminals lack the usual features of a presynaptic dendrite. It has been shown
      that in this nucleus some round vesicle terminals, especially those postsynaptic
      to flattened vesicle terminals, are primary afferents from the periphery.
      Therefore the round vesicle terminal presynaptic to the axon hillock-initial
      segment region, some of which are included in the axo-axo-axonic complex may also
      be a primary afferent directly contacting the spike generator area of the relay
      neuron and under presynaptic control of a flattened vesicle synapse. The latter
      may possibly be an intrinsic contact. This strategic situation of round vesicle
      terminals and the axo-axo-axonic complex at the axon hillock or initial segment
      has major implications relevant to the overall output of these neurons.

PMID- 8270961
TI  - Routes of excretion of neuronal lysosomal dense bodies after ventricular infusion
      of leupeptin in the rat: a study using ubiquitin and PGP 9.5 immunocytochemistry.
AB  - To determine the rate and routes of removal of lysosomal, lipofuscin-like dense
      bodies from neurons, the protease inhibitor, leupeptin, was infused into the
      lateral ventricle of rats for up to nine days. After seven days a number of
      animals were then allowed to recover. The formation and later disappearance of
      dense bodies was followed by morphology and immunocytochemistry. After 48 h of
      infusion lysosomal dense bodies in large numbers appeared in cortical,
      hippocampal and cerebellar neurons, which also showed increased ubiquitin
      immunoreactivity, as well as in other cell types. By 3-4 days ubiqutin
      immunoreactive dense bodies were equally distributed between neurons and
      astroglia. After seven to nine days of infusion ubiquitin immunoreactive dense
      bodies filled neuronal perikarya, dendrites and expanded initial segments of many
      axons and were abundant in glial processes. All dense bodies studied by electron
      microscopy were ubiquitin immunoreactive. After four days of recovery dense
      bodies were markedly fewer in neuronal perikarya, and virtually all were now
      within glial processes. From 7 to 28 days of recovery, when most neurons appeared
      normal, lipofuscin bodies remained in axon initial segments and in reduced
      numbers in glial processes, particularly around blood vessels and beneath the pia
      of hippocampus and of cerebellar cortex. Thus, neurons probably have a steady
      passage of short lived proteins through the lysosomal excretory pathway. The
      observed temporal sequence of events on recovery suggests that secondary
      lysosomes probably pass rapidly from neuronal perikarya and dendrites to
      astrocytes and thus to the vascular bed or pia-arachnoid. The mechanism of cell
      to-cell transfer is not clear from this study.

PMID- 8270963
TI  - The emergence of the cortical GABAergic neuron: with particular reference to some
      peptidergic subpopulations.
AB  - The technical developments which have led to our present ability to make
      predictions about neurochemical identity from morphological observations are
      retraced with particular reference to the GABAergic neuron and its many
      subdivisions. The synaptology of four peptidergic sub-populations in the cerebral
      cortex is examined and described in detail. It is concluded that the recognition
      of Gray Type 1 and Type 2 synapse types continues to provide a key element in our
      analysis and understanding of the connectivity of the CNS.

PMID- 8270964
TI  - Some aspects of the synaptic circuitry underlying inhibition in the ventrobasal
      thalamus.
AB  - We describe here, and review, the ultrastructural features and synaptic
      relationships of flat-vesicle containing, presumptively inhibitory presynaptic
      elements in the glomerular and extraglomerular neuropils of the thalamic
      ventrobasal (VB) nucleus in monkey, cat and rat. This account is based on EM
      study of normal material, LM and EM immunocytochemistry for GABA, anterograde
      tracing with HRP and EM of physiologically characterized interneurons
      intracellularly injected with HRP. It emerges clearly from this study that
      attempts to categorize flat-vesicle containing terminals in thalamic tissue as
      either F-boutons (axon terminals with flattened synaptic vesicles and Gray type
      II synaptic specializations) or P-boutons (dendritic appendages of interneurons
      with flattened vesicles) by examining only single sections are likely to produce
      unreliable results. In many cases it is only by studying serial sections that
      such profiles can be unambiguously identified. Within glomeruli the P-boutons
      participate in triplet (triadic) synapses which are thought to mediate rapid feed
      forward inhibition of projection cells, and serial synaptic arrays involving
      other P-boutons. Since P-boutons from more than one interneuron are present in
      individual VB glomeruli, P-bouton to P-bouton synapses may mediate disinhibition
      of interneurons. We show that dendritic shafts of interneurons make and receive
      synaptic contacts and that in the monkey, at least, reciprocal synaptic contacts
      between shafts or between a shaft and a P-bouton are not uncommon. Finally, we
      confirm that in the rat VB there are insignificant numbers of P-boutons or cells
      with the morphological and transmitter characteristics of interneurons and we
      suggest that comparative electrophysiological studies of inhibitory events in rat
      VB versus those in cat or monkey VB during transmission of somatosensory
      information might help to clarify the roles of thalamic intrinsic neurons.

PMID- 8270965
TI  - Effect of decentralization or contralateral ganglionectomy on obstruction-induced
      hypertrophy of rat urinary bladder muscle and pelvic ganglion.
AB  - After urethral obstruction the musculature of the rat urinary bladder undergoes
      extensive hypertrophy, irrespective of whether its innervation is intact or
      whether one of the two pelvic ganglia has been decentralized or excised. Even the
      excision of both ganglia does not inhibit muscle hypertrophy. The presence of
      nerves is not a prerequisite for the muscle growth to occur. The stimulus for
      growth resides in the bladder itself, and the present and previous observations
      are in agreement with the notion that the distension of the muscle is a primary
      stimulus for muscle growth. With bladder hypertrophy, the pelvic ganglion neurons
      undergo hypertrophy, even when they are devoid of their preganglionic input.
      Synaptic connection with the preganglionic fibres and stimuli from the spinal
      cord are not prerequisites for neuronal hypertrophy. However, the hypertrophy is
      less marked in the decentralized ganglion neurons than in the neurons of the
      contralateral intact ganglion. With bladder hypertrophy and contralateral
      ganglionectomy, the neuronal hypertrophy is greater than with either procedure
      alone, suggesting that the two forms of neuronal growth stimulation can be added
      to each other.

PMID- 8270966
TI  - Intravesical therapy for superficial bladder cancer: is it a wash?

PMID- 8270967
TI  - Home antibiotic therapy for low-risk cancer patients with fever and neutropenia:
      a pilot study of 30 patients based on a validated prediction rule.
AB  - PURPOSE: To assess the feasibility of early discharge to home therapy with
      standard intravenous antibiotics in 30 patients with fever and neutropenia at low
      risk by a validated clinical decision rule. PATIENTS AND METHODS: Newly admitted
      outpatients with fever and neutropenia were evaluated for home therapy during 2
      days of inpatient observation. To evaluate enrolled patients' acceptance of home
      care, we assessed patient attitudes and quality of life before and after home
      therapy. To assess economic effects, we compared the medical charges of patients
      treated at home with those of medically eligible patients who remained in the
      hospital. RESULTS: Of the first 84 patients, 50 (60%) were medically ineligible,
      and neutropenia was resolved in another eight (10%) during the observation
      period. Only nine patients of the remaining 26 who were medically eligible (35%)
      were enrolled in the home-therapy trial. Thereafter, 21 of 31 medically eligible
      patients (68%) were enrolled. The 30 patients treated at home were neutropenic
      for a median of 6 days (mean, 8.2). Four had medical complications, and five
      others were readmitted for observation. Patients' quality of life improved during
      home therapy, and favorable attitudes toward home care persisted after treatment.
      Medically eligible patients not enrolled had briefer neutropenia than patients
      treated at home, but had 44% higher daily medical charges and equivalent overall
      charges despite treatment half as long. CONCLUSION: We conclude that early
      discharge of low-risk patients to home intravenous antibiotic therapy is
      feasible, is well received by patients, and may prove to be cost-saving. However,
      these conclusions must be validated in a large randomized trial.

PMID- 8270968
TI  - Chemotherapy for induction of remission of childhood acute myeloid leukemia
      followed by marrow transplantation or multiagent chemotherapy: a report from the
      Childrens Cancer Group.
AB  - PURPOSE: In an effort to evaluate the usefulness of bone marrow transplantation,
      the Childrens Cancer Group (CCG) initiated a multiinstitutional study comparing
      bone marrow transplantation versus chemotherapy after successful induction of
      remission for previously untreated children and young adults with acute myeloid
      leukemia. PATIENTS AND METHODS: From 1979 to 1983, 508 patients were entered onto
      this study and 490 were treated. After induction, patients with an HLA mixed
      leukocyte culture (MLC)-compatible sibling underwent bone marrow transplantation.
      Patients not eligible for bone marrow transplantation were eligible for
      randomization to two chemotherapy maintenance regimens. All patients undergoing
      bone marrow transplantation were conditioned with cyclophosphamide and total-body
      irradiation (TBI). Methotrexate was used to prevent or modify graft-versus-host
      disease (GVHD). RESULTS: Three hundred eighty-one patients achieved bone marrow
      remission (78%). Eighty-nine patients had an HLA/MLC-compatible sibling donor and
      were eligible for bone marrow transplantation, and 252 had no match. Comparison
      of survival estimates for patients eligible for transplantation versus not
      eligible at 3 years (52% v 41%), 5 years (50% v 36%), and 8 years (47% v 34%)
      showed a significant difference in favor of bone marrow transplantation (P <
      .05). Disease-free survival (DFS) demonstrated similar results. Application of a
      cure model to the results showed a better outcome for those eligible for
      transplantation (P = .04). Patients randomized between the two chemotherapy
      regimens did not show any significant difference between those treated with a
      continuous maintenance versus a cyclic regimen (P = .16). CONCLUSION: Children
      and young adults who successfully achieved a remission with multiple-agent
      chemotherapy who had an HLA/MLC-compatible donor and were thus eligible for an
      allogeneic bone marrow transplant had better survival than those not eligible for
      transplantation.

PMID- 8270969
TI  - Successful Pneumocystis carinii pneumonia prophylaxis using aerosolized
      pentamidine in children with acute leukemia.
AB  - PURPOSE: We report our experience replacing trimethoprim-sulfamethoxazole
      (TMP/SMX) with aerosolized pentamidine (AP) in 22 children with acute leukemia
      who could not tolerate TMP/SMX. PATIENTS AND METHODS: Children (age 1 to 15
      years) with acute leukemia during maintenance chemotherapy or post-bone marrow
      transplantation (BMT) receiving prophylaxis for Pneumocystis carinii pneumonia
      (PCP) with TMP/SMX received AP following prolonged neutropenia or allergy to
      TMP/SMX. Patients received 300 mg of AP monthly (children < 4 years received 150
      mg) dissolved in 5 mL of distilled water over 20 to 30 minutes. RESULTS: Over a 3
      year period, 358 courses of AP were administered over 10,124 observable days. AP
      was adequately tolerated on a monthly basis for prophylaxis against PCP in 22
      children with acute leukemia. AP was demonstrated to be effective in preventing
      PCP. There were minimal side effects observed during this trial. The majority of
      children with acute lymphoblastic leukemia (ALL; 12 of 14 [86%]) undergoing
      maintenance chemotherapy were able to resume full-dose therapy. CONCLUSION: AP in
      children is well tolerated and shows high efficacy for PCP prophylaxis in
      children with leukemia. We conclude that AP should be considered as second-line
      PCP prophylactic therapy for children with acute leukemia in instances in which
      TMP/SMX cannot be tolerated. Phase III trials are required to determine its
      effect on dose intensification and event-free survival.

PMID- 8270970
TI  - Escalating dose of mitoxantrone with high-dose cyclophosphamide, carmustine, and
      etoposide in patients with refractory lymphoma undergoing autologous bone marrow
      transplantation.
AB  - PURPOSE: We conducted a dose-finding study of mitoxantrone (MITO) in combination
      with high-dose cyclophosphamide, carmustine (BCNU), and etoposide (CBV) in
      refractory lymphoma undergoing autologous bone marrow transplantation (ABMT). The
      objective were to determine the following: (1) the maximum-tolerated dose of
      MITO, (2) the extramedullary toxicity of this regimen, (3) its antitumor
      activity, and (4) the pharmacokinetic characteristics of MITO at each dose level.
      PATIENTS AND METHODS: Escalating doses of MITO (15 to 90 mg/m2, single bolus
      infusion on day -8) followed by CBV were administered to 20 patients (mean age,
      38.5 years) with refractory lymphoma. MITO concentrations were determined by high
      performance liquid chromatography (HPLC). RESULTS: No toxic death occurred. The
      maximum-tolerated dose appears to be 75 mg/m2. Two of five patients treated with
      90 mg/m2 developed severe organ toxicity, versus zero of 15 treated with doses up
      to 75 mg/m2. Duration of neutropenia was longer for patients treated with 90
      mg/m2 (31.7 days) than for patients treated with doses up to 75 mg/m2 (22.1 days)
      (P < .05). A linear relationship was observed between administered dose of MITO
      and (1) plasma peak value, (2) area under the curve (AUC), and (3) plasma
      concentration on the day of marrow infusion (day 0). Hematologic toxicity was
      related to the terminal half-life (T1/2) of MITO, and day-0 plasma concentration.
      A high complete response (CR) rate was observed (60%), and eight of 11 (73%)
      patients treated with MITO > or = 60 mg/m2 achieved a CR. CONCLUSION: MITO (up to
      75 mg/m2) and CBV can be administered with acceptable toxicity and a promising CR
      rate in this poor-risk population, justifying further phase II studies.

PMID- 8270971
TI  - Clinical significance of bcl-2-MBR gene rearrangement and protein expression in
      diffuse large-cell non-Hodgkin's lymphoma: an analysis of 83 cases.
AB  - PURPOSE: The goal of this study was to assess the prognostic significance of a
      rearrangement of the major breakpoint region of the bcl-2 gene and/or expression
      of bcl-2 protein in diffuse large-cell lymphomas of B-cell origin. PATIENTS AND
      METHODS: All 83 patients diagnosed at the Cross Cancer Institute between 1987 and
      1992 with malignant lymphoma (ML), diffuse large-cell ML non-cleaved-cell ML or
      cleaved-cell ML, or with diffuse large-cell immunoblastic ML were studied. bcl-2
      rearrangement was identified by a polymerase chain reaction technique. This
      technique detects the approximately 60% of rearrangements involving the major
      breakpoint region bcl-2 gene (bcl-2-MBR). bcl-2 protein expression was studied by
      immunohistochemistry. RESULTS: More than 66% of the cases expressed bcl-2
      protein, whereas 18% had a detectable bcl-2-MBR gene rearrangement. Overall,
      cases with bcl-2-MBR rearrangement had shorter disease-free periods. Cases with
      nodal and extranodal presentation had a similar frequencies of bcl-2-MBR
      rearrangement; however, the disease-free period of patients with extranodal
      presentation and bcl-2-MBR rearrangement was significantly shorter than that of
      those without rearrangement. CONCLUSION: bcl-2 protein is frequently expressed in
      diffuse large-cell lymphomas, but does not influence prognosis. The bcl-2-MBR
      gene rearrangement may possibly be associated with a shorter disease-free period,
      particularly in the specific setting of a lymphoma with extranodal presentation.

PMID- 8270972
TI  - Transdermal clonidine for ameliorating tamoxifen-induced hot flashes.
AB  - PURPOSE: To determine the efficacy of transdermal clonidine for alleviating
      tamoxifen-induced hot flashes in women with a history of breast cancer. PATIENTS
      AND METHODS: A randomized, double-blind, crossover design was used in this
      prospective study. Women with a history of breast cancer who were receiving
      tamoxifen and suffering from hot flashes were potentially eligible for this
      protocol study. RESULTS: Clonidine did reduce hot-flash frequency to a degree
      that was statistically impressive (P < .0001), but clinically moderate (20%
      reduction from baseline). It also decreased hot-flash severity (P = .02, 10%
      reduction from baseline). Clonidine was related to increased mouth dryness (P <
      .001), constipation (P < .02), itchiness under the patch (P < .01), and
      drowsiness (P < .05). CONCLUSION: Better means are needed to alleviate hot
      flashes among patients in whom estrogen therapy is contraindicated.

PMID- 8270973
TI  - Unilateral nephrectomy and cisplatin as risk factors of ifosfamide-induced
      nephrotoxicity: analysis of 120 patients.
AB  - PURPOSE: This study was performed to identify risk factors of ifosfamide-induced
      renal damage. PATIENTS AND METHODS: Renal function was assessed in 120 patients
      at a minimum of 3 months after completion of chemotherapy including ifosfamide.
      The cumulative ifosfamide dose ranged from 2 to 95 g/m2 (median, 30 g/m2). Ten
      patients had undergone unilateral nephrectomy; combination cytostatic treatment
      included cisplatin in 51 and methotrexate in 57. Sixty-eight patients had
      received gentamicin treatment. The glomerular filtration rate was estimated using
      the Schwartz formula. Proximal tubular function was assessed by the percent
      reabsorptions of glucose and 16 amino acids, the fractional excretion of sodium,
      and the fractional reabsorption of phosphate. In addition, the serum bicarbonate
      level was measured. RESULTS: Proximal tubular dysfunction--with a predominance of
      renal amino acid (66.3%) and phosphate loss (38.3%)--was much more frequent than
      both glomerular impairment and acidosis. Seven patients were identified as having
      renal Fanconi's syndrome, and generalized tubulopathy was noted in another 15
      patients. Ifosfamide-induced nephrotoxicity was dose-dependent, with a weak
      linear inverse correlation between cumulative ifosfamide dose and fractional
      phosphate reabsorption. Unilateral nephrectomy proved to be the single most
      important risk factor (odds ratio for the development of renal Fanconi's
      syndrome, 11.4), but cisplatin also significantly enhanced ifosfamide-mediated
      nephrotoxicity. Methotrexate, gentamicin, and patient age at primary diagnosis
      had no influence on renal function. CONCLUSION: Ifosfamide chemotherapy should
      probably be restricted in patients after unilateral nephrectomy.

PMID- 8270974
TI  - Suramin: development of a population pharmacokinetic model and its use with
      intermittent short infusions to control plasma drug concentration in patients
      with prostate cancer.
AB  - PURPOSE: This study aimed to (1) develop a population pharmacokinetic model for
      suramin; (2) use Bayesian methods to assess suramin pharmacokinetics in
      individual patients; (3) use individual patients' pharmacokinetic parameter
      estimates to individualize suramin dose and schedule and maintain plasma suramin
      concentrations within predetermined target ranges; and (4) assess the feasibility
      of outpatient administration of suramin by intermittent, short infusions.
      METHODS: Plasma suramin concentrations were measured by high-performance liquid
      chromatography (HPLC), and compartmental pharmacokinetic models were fit using a
      Bayesian algorithm. Population pharmacokinetic models were developed using an
      iterative two-stage approach. Estimates of each patient's central-compartment
      volume were used to calculate suramin dosage. Simulation of that patient's
      suramin clearance was used to predict the time of his next dose. Using this
      approach, plasma suramin concentration was maintained at between 200 and 300, 175
      and 275, 150 and 250, or 100 and 200 microgram/mL in four sequential patient
      cohorts. The ability of two- and three-compartment, open, linear models to fit
      the pharmacokinetic data was compared. Population pharmacokinetic parameters were
      estimated, using both two- and three-compartment structural models in 69 hormone
      refractory prostate cancer patients. RESULTS: Target plasma suramin
      concentrations in individual patients were rapidly achieved. Concentrations were
      maintained within desired ranges for > or = 85% of treatment duration in all
      cohorts. A three-compartment, open, linear model described suramin
      pharmacokinetics better than did a two-compartment, open, linear model.
      Population pharmacokinetic estimates generated for two- and three-compartment
      pharmacokinetic models demonstrated modest interpatient pharmacokinetic
      variability and the long terminal half-life of suramin. CONCLUSION: Suramin can
      be administered by intermittent short infusion. Adaptive-control-with-feedback
      dosing facilitated precise control of plasma suramin concentrations and allowed a
      number of different concentration ranges to be studied. This approach is
      expensive and labor-intensive. Although we have demonstrated the ability to
      control drug exposure, simpler dosing schedules require critical evaluation.
      Population pharmacokinetic parameters generated in men with hormone-refractory
      prostate cancer will facilitate rational design of such schedules.

PMID- 8270975
TI  - Phase I clinical and pharmacokinetic study of high-dose mitoxantrone combined
      with carboplatin, cyclophosphamide, and autologous bone marrow rescue: high
      response rate for refractory ovarian carcinoma.
AB  - PURPOSE: To develop an active high-dose chemotherapy regimen for the treatment of
      ovarian carcinoma. Due to the rapid development a drug resistance, conventional
      chemotherapy cures only 20% of patients with advanced disease. However, in vitro
      data demonstrate a steep dose-response curve to a variety of agents, most notably
      mitoxantrone. PATIENTS AND METHODS: A phase I study of escalated bolus
      mitoxantrone (10 to 25 mg/m2 x 3) and cyclophosphamide (30 to 50 mg/kg x 3) with
      a 5-day infusion of carboplatin (1,500 mg/m2) and an autologous bone marrow
      transplant (ABMT) was performed. Mitoxantrone pharmacokinetics were performed to
      document levels required to kill platinum-resistant ovarian carcinoma in vitro.
      RESULTS: We treated 25 patients; the maximum-tolerated total doses (MTD) were 75
      mg/m2 for mitoxantrone, 120 mg/kg for cyclophosphamide, and 1,500 mg/m2 for
      carboplatin. The dose-limiting toxicity was gastrointestinal, with severe
      diarrhea, ileus, and resulting sepsis. Transient partial deafness was seen in
      four patients, and acute renal failure (ARF) occurred in one patient at the first
      dose level, but was eliminated in subsequent patients with aggressive hydration.
      There were four early deaths due to ARF (n = 1), Legionella pneumonia (n = 1),
      and sepsis (n = 2). Peak mitoxantrone levels at the MTD were 623 to 2,810 ng/mL,
      and the area under the curve (AUC) values of the concentration versus time
      measurements were 560 to 1,700 ng/mL/h. Of 20 assessable patients, 65% responded,
      with a 45% complete remission (CR) rate. All six of the assessable patients with
      ovarian cancer responded: CR in five (83%) and partial remission (PR) in one
      (17%); the CRs have lasted 7 to 30+ months. Responses were also seen in
      testicular and breast carcinoma. CONCLUSION: This regimen was well tolerated at
      the MTD and appears promising for relapsed/refractory ovarian carcinoma, with
      mitoxantrone levels achieved that are active in vitro against platinum-resistant
      ovarian carcinoma cells.

PMID- 8270976
TI  - Phase I trial of murine monoclonal antibody 14G2a administered by prolonged
      intravenous infusion in patients with neuroectodermal tumors.
AB  - PURPOSE: The purpose of this phase I trial was to determine the toxicity and
      maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2)
      in cancer patients. PATIENTS AND METHODS: Following tracer doses of iodine-131
      labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma,
      neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations
      of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days.
      RESULTS: The overall sensitivity of external immunoscintigraphy was 64 of 74
      known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of
      severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and
      chronic refractory postural hypotension (two patients). Toxicity was less severe
      in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients
      developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life
      (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and
      39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma
      patients were positive for GD2 antigen, but only two of six had trace amounts of
      14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two
      partial responses (PRs; neuroblastoma) were observed. CONCLUSION: Mab 14G2a has
      modest antitumor activity at the expense of significant toxicity. Dose-limiting
      neurologic sequelae may significantly limit phase II studies other than in
      pediatric patients with neuroblastoma.

PMID- 8270977
TI  - Phase I clinical trial of intravenous L-buthionine sulfoximine and melphalan: an
      attempt at modulation of glutathione.
AB  - PURPOSE: A phase I dose-escalation trial of intravenous (IV) L-buthionine-SR
      sulfoximine (BSO) with melphalan (L-PAM) was performed to determine the toxicity
      and biologic activity of BSO, administered as a short infusion every 12 hours,
      and the combination of BSO plus L-PAM. PATIENTS AND METHODS: Twenty-eight
      patients with refractory malignancies received 30-minute infusions of BSO every
      12 hours for 6 to 10 doses in week 1 followed in week 2 by either IV L-PAM (15
      mg/m2) alone or BSO as in week 1 with L-PAM. Patients received the combination in
      week 5 (course no. 2) if they received L-PAM alone during week 2 and vice versa.
      BSO doses ranged from 1.5 g/m2 to 13.104 g/m2. RESULTS: The only toxicity
      observed with BSO infusions was occasional nausea/vomiting. Evaluation of 23
      paired courses (L-PAM plus BSO v L-PAM) showed significantly (P < .001) greater
      leukopenia and thrombocytopenia with L-PAM plus BSO. No other significant
      toxicity was noted. Measurement of intracellular glutathione (GSH) levels in
      peripheral mononuclear cells (PBLs) of all patients receiving BSO showed a
      consistent, non-dose-dependent, linear decrease in GSH with repeated BSO doses.
      Maximal GSH depletion (40% of baseline values, absolute values 200 to 250
      ng/10(6) PBLs) was noted after the sixth BSO dose; extended BSO dosing schedules
      beyond six total BSO doses did not further deplete GSH. Evaluation of gamma
      glutamylcysteine synthetase (GCS) activity showed marked inhibition near the end
      of each infusion with near complete recovery of GCS activity before the next BSO
      dose. The pattern of GCS inhibition mirrored the plasma BSO concentrations with
      peak values (level 6, 4 to 8 mmol/L L,R+L,S BSO) observed at the end of the
      infusion with a rapid decrease in plasma concentrations with an estimated half
      life (t1/2) of less than 2 hours. Differential elimination of the R+S
      stereoisomers was observed. Analysis of L-PAM pharmacokinetics showed marked
      interpatient variability and a significant decrease in total-body clearance (P =
      .01) and volume of distribution (P = .03) in courses with L-PAM plus BSO as
      compared with L-PAM alone. CONCLUSION: This study shows that BSO alone and in
      combination with L-PAM can be safely given to patients, but that a schedule of
      short infusions every 12 hours does not result in GSH depletion less than 30% of
      baseline values.

PMID- 8270978
TI  - Patterns of failure following surgical resection of renal cell carcinoma:
      implications for adjuvant local and systemic therapy.
AB  - PURPOSE: This report is a patterns-of-failure analysis of resected renal cell
      carcinoma (RCC) performed to determine the relative incidences of local failure
      (LF) and distant failure, to identify the pathologic features predicting for each
      using a multivariate analysis, and to assess the relative impact of each form of
      failure on overall survival (OS). In this way, the potential value of and
      selection of patients for adjuvant local and/or systemic therapy can be better
      evaluated. MATERIALS AND METHODS: The records of 172 patients with unilateral,
      nonmetastatic RCC who were treated with definitive surgery between 1978 and 1988,
      and who had a minimum follow-up duration of 1 year, were identified through the
      Memorial Sloan-Kettering tumor registry. Distribution by stage included T1, 10
      patients; T2, 102; T3a, 32; T3b, 27; and T4, one. The incidences of positive
      lymph nodes (LNs) and positive margins were 5.8% and 6.4%, respectively. RESULTS:
      LF developed in only six patients, yielding a 7-year actuarial incidence of 5%.
      In this subset, four patients developed distant metastases (DM), three occurring
      concurrently with or before LF. DM developed in 30 patients, yielding a 7-year
      actuarial incidence of 26%. Among the variables that had an impact on the
      development of DM according to univariate log-rank tests, only positive LNs (P =
      .026) and renal vein extension (P = .001) remained as significant independent
      prognosticators. The overall 7-year actuarial survival rate was 80%. Eleven
      patients died of RCC during follow-up, nine of whom (82%) died of metastatic
      disease. CONCLUSION: LF is rare following surgical management of RCC, and shows
      no clear causal relationship with the development of DM. Patients die of DM, and
      not LF. These data do not support the role of adjuvant radiation therapy in this
      disease. Patients with LN involvement or renal vein extension have a
      significantly increased risk for developing DM, and are therefore appropriate
      candidates for trials investigating systemic therapy.

PMID- 8270979
TI  - Early evaluation of combined fluorouracil and leucovorin as a radiation enhancer
      for locally unresectable, residual, or recurrent gastrointestinal carcinoma. The
      North Central Cancer Treatment Group.
AB  - PURPOSE: To develop a tolerable regimen of fluorouracil (5-FU), low-dose
      leucovorin, and radiation, and to obtain an early estimate of therapeutic
      effectiveness. PATIENTS AND METHODS: Forty patients with locally unresectable or
      recurrent gastrointestinal carcinoma were studied (pancreas, n = 22; rectum and
      sigmoid, n = 10; gastric, n = 6; other, n = 2). Irradiation therapy was
      administered in 1.8-Gy fractions 5 days per week, with total doses ranging from
      45 to 54 Gy. 5-FU 400 mg/m2/d plus leucovorin 20 mg/m2/d, both by rapid
      intravenous injection, were administered for 3 or 4 days during the first and
      fifth weeks of radiation. 5-FU 425 mg/m2/d plus leucovorin 20 mg/m2/d were
      administered for 4 days at 4 weeks following radiation and for 5 days at 9 weeks.
      RESULTS: Major toxicities with upper abdominal treatment were nausea, vomiting,
      weight loss, and leukopenia. A tolerable dosage regimen was radiation at 45 Gy
      with 4 days of 5-FU plus leucovorin during the first week and 3 days during the
      last week with postradiation chemotherapy. Major toxicities with pelvic radiation
      were diarrhea and leukopenia. A tolerable regimen was 54 Gy with 4 days of 5-FU
      plus leucovorin during the first and fifth week followed by the postradiation
      chemotherapy. Median survival durations for pancreatic and rectal/sigmoid
      carcinomas are 13 months and 31 months, respectively. Five patients have no
      evidence of disease from 38 to 50 months after the onset of therapy (rectal, n =
      2; stomach, n = 2; pancreas, n = 1). CONCLUSION: We have developed patient
      tolerable regimens for combined 5-FU plus leucovorin followed by radiation to the
      abdomen and to the pelvis. The favorable results observed in locally unresectable
      disease allow cautious optimism for possible effectiveness in the surgical
      adjuvant setting, a possibility currently being tested in national trials of
      rectal and gastric carcinoma.

PMID- 8270980
TI  - The cancer anorexia-cachexia syndrome.
AB  - PURPOSE: To review the research related to the anorexia-cachexia syndrome in
      patients with cancer, with attention to the etiology and symptomatic treatment.
      DESIGN: A comprehensive literature review using MEDLINE. RESULTS AND CONCLUSION:
      The anorexia-cachexia syndrome is a common problem in advanced cancer. Although
      many possible etiologies have been investigated, the cause has not been
      determined. Appropriate clinical evaluation is necessary to identify those
      patients who may respond to available, symptomatic treatments.

PMID- 8270981
TI  - WR-2721 and hypocalcemia.

PMID- 8270982
TI  - Reinduction with the same cytostatic treatment in patients with metastatic breast
      cancer: an Eastern Cooperative Oncology Group study.
AB  - PURPOSE: To investigate the therapeutic value of reinduction with the same
      cytostatic treatment that had been used in induction treatment for women with
      metastatic breast cancer. MATERIALS AND METHODS: One hundred six women with
      metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin,
      vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction
      treatment, then randomized to receive one of two chemotherapy regimens if they
      had obtained an induction partial response (PR) or no change (NC), or to receive
      observation versus chemotherapy if they had obtained an induction complete
      response (CR). Patients were then retreated with DAVTH reinduction after relapse.
      RESULTS: Seventy-four patients were eligible or had minor reasons for
      ineligibility. Severe or life-threatening toxicity was documented in 46%, and
      lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16
      induction nonresponders, 15% induction PR, 44% induction CR). The median time to
      treatment failure (TTF) from reinduction was 3 months, and the median survival
      duration from reinduction was 14 months. In a logistic model, factors associated
      with more reinduction responses were observation after induction CR (P = .002)
      and age greater than 55 years (P = .04). Time since induction was not
      significant. CONCLUSION: Reinduction of response after treatment failure remains
      a therapeutic problem. The need for better salvage treatment underlines the
      importance of developing new regimens.

PMID- 8270983
TI  - High-dose therapy: here to stay or just visiting?

PMID- 8270984
TI  - Bioequivalence of 20-mg once-daily tamoxifen relative to 10-mg twice-daily
      tamoxifen regimens for breast cancer.
AB  - PURPOSE: We studied the bioequivalence of a new once-daily regimen of tamoxifen
      citrate relative to the standard twice-daily regimen of tamoxifen citrate, an
      established antiestrogenic treatment for breast cancer. PATIENTS AND METHODS: Of
      30 women with breast cancer, 27 completed this open, two-period, crossover
      randomized trial. During one 3-month period, patients took one standard 10-mg
      tamoxifen tablet twice daily; during the preceding or following 3-month period,
      patients took one of the new 20-mg tablets once daily. Pharmacokinetic profiles
      and safety parameters were assessed at the end of each 3-month treatment period.
      RESULTS: Overall, measured concentrations of tamoxifen and its principal active
      metabolite, N-desmethyltamoxifen, remained relatively constant over the 24-hour
      sampling periods at the end of each treatment sequence. For both compounds, the
      percentage differences of the geometric means for all pharmacokinetic parameters
      indicated bioequivalence of the once-daily regimen of tamoxifen relative to the
      standard twice-daily regimen. Both treatment sequences were well tolerated;
      reported adverse events occurred at similar frequencies with the two treatment
      regimens. CONCLUSION: The 20-mg tamoxifen tablet taken once daily was
      bioequivalent to the 10-mg tamoxifen tablet taken twice daily, with no difference
      in relative risk. The once-daily treatment is a simpler regimen and may
      facilitate compliance, which may enhance therapeutic outcomes during long-term
      treatment of breast cancer.

PMID- 8270985
TI  - Oral etoposide is active against platinum-resistant epithelial ovarian cancer.
AB  - PURPOSE: To determine whether etoposide (VP16) is more effective when
      administered on a chronic schedule, women with clinically defined platinum
      resistant epithelial ovarian cancer (EOC) were studied. PATIENTS AND METHODS:
      Thirty-one eligible women were treated with oral VP16. The first seven received a
      dose that varied depending on their body-surface area, but this proved too toxic,
      and so a fixed dose of 100 mg orally per day for 14 days every 3 weeks was used
      for the other subjects. RESULTS: The response rate was 26% (95% confidence
      interval [CI], 11% to 41%). The 28 women with cancer that had progressed while
      they were receiving a platinum analog had a response rate of 21% (95% CI, 6% to
      36%). Response durations were short. CONCLUSION: When administered on this
      chronic schedule, VP16 has activity against platinum-resistant EOC.

PMID- 8270986
TI  - Prognostic significance of p53 immunostaining in epithelial ovarian cancer.
AB  - PURPOSE: To evaluate the prognostic significance of p53 expression in epithelial
      ovarian cancer, including a subset of stage I patients, and to look for
      correlations between p53 expression and other disease parameters, including
      stage, grade, age, histologic subtype, second-look results, ploidy, and percent S
      phase. PATIENTS AND METHODS: We analyzed p53 expression in 284 patients with
      epithelial ovarian cancer using immunohistochemical techniques in paraffin
      embedded specimens. There were 36 patients with stage I disease, 20 with stage II
      disease, 186 with stage III disease, and 42 with stage IV disease. RESULTS: p53
      immunoreactivity was present in 177 cases (62%). p53 expression was associated
      with grade 3 to 4 disease (P = .003). The following factors were associated with
      a decrease in overall survival in a univarate analysis: stage III or IV disease
      (P = .0001), grade 3 or 4 disease (P = .0001), age above the median (P = .0002),
      and p53 reactivity (P = .04). In a multivariate analysis, stage, grade, and age
      retained independent prognostic significance. In the subset of 36 stage I
      patients, p53 positively approached statistical significance (P = .10) as a
      negative prognostic factor in a univariate analysis. CONCLUSION: Abnormalities of
      p53 expression occur commonly in epithelial ovarian cancer. Although associated
      with decreased survival in a univariate analysis, this biologic marker did not
      retain independent prognostic significance in a multivariate analysis. p53
      expression should be studied in a larger cohort of early-stage patients, where
      accurate prognostic information is needed to direct therapy.

PMID- 8270987
TI  - Prophylaxis of superficial bladder cancer with mitomycin or interferon alfa-2b:
      results of a multicentric Italian study.
AB  - PURPOSE: Interferons have shown a definite activity in the intravesical treatment
      of residual papillary bladder cancer or carcinoma in situ (CIS). The purpose of
      the present study was to investigate the efficacy of interferon alfa-2b (IFN) as
      prophylactic treatment of superficial bladder cancer. PATIENTS AND METHODS: Two
      hundred eighty-seven patients with primary pTa G2, pT1 G1 to G2 superficial
      bladder cancer, following complete transurethral resection (TUR), were randomly
      allocated to receive intravesical treatment, either with IFN (50 x 10(6) IU) or
      mitomycin (MIT-C; 40 mg). Drugs were instilled on a weekly basis for a total of 8
      weeks. RESULTS: MIT-C was superior to IFN treatment with respect to time to
      recurrence, relative recurrence rate, recurrence rate per 100 patients per month,
      and recurrence tumor rate per 100 patients per month. This difference was
      particularly evident in patients with pTa G2 tumors. After multivariate analysis,
      the number of primary tumors and tumor grade were the best predictors of
      recurrence, while allocated treatment had only a moderate effect. Intravesical
      treatment was well tolerated in both arms. However, more local toxicity was
      experienced by patients treated with MIT-C. On the other hand, fever occurred
      significantly more frequently in patients treated with IFN. CONCLUSION: IFN was
      less effective, although locally better tolerated, than MIT-C as prophylactic
      treatment of primary superficial bladder cancer.

PMID- 8270988
TI  - Sequencing and schedule effects of cisplatin plus etoposide in small-cell lung
      cancer: results of a North Central Cancer Treatment Group randomized clinical
      trial.
AB  - PURPOSE: The combination of etoposide (E) and cisplatin (P) is an accepted
      standard therapy for small-cell lung cancer (SCLC); however, the optimal
      sequencing and administration schedule has not been defined. This study was
      designed to evaluate different sequencing and administration schedules of E and P
      in the treatment of SCLC. PATIENTS AND METHODS: Five hundred fifty-two eligible
      patients with limited-(LD) and extensive-stage (ED) SCLC were randomized to
      receive one of the following regimens: arm A, P 30 mg/m2 by intravenous (IV)
      bolus followed by E 130 mg/m2 bolus; arm B, E 130 mg/m2 bolus followed by P 30
      mg/m2 bolus; arm C, E 130 mg/m2 by 24-hour infusion and P 30 mg/m2 bolus at the
      end of each 24-hour infusion of E; arm D, E 130 mg/m2 by 24-hour infusion and P
      45 mg/m2 by 24-hour infusion on day 2 and 3 only. Two 3-day induction cycles of
      IV EP were administered 4 weeks apart. Subsequent therapy was the same for all
      arms, consisting of four cycles of cyclophosphamide, doxorubicin, and vincristine
      (CAV) at 4-week intervals. Consolidative thoracic radiation therapy (TRT) and
      prophylactic cranial irradiation (PCI) were administered to responders. RESULTS:
      The overall response rate (84%) was similar in all treatment arms. Treatment arm
      A was associated with the best complete response (CR) rate (52%), the most
      favorable median survival time (MST) of 15 months, and a 26% 2-year survival
      rate. Patients with LD on arm A had a MST of 20 months and a 42% 2-year survival
      rate. Multivariate analysis indicated that extent of disease, performance status,
      arm of therapy, and sex were significant independent factors influencing
      survival. Toxicity of the four regimens was similar, except for greater
      thrombocytopenia on arm D. CONCLUSION: The bolus administration of EP with E
      following P for the first two cycles of chemotherapy was the most effective
      regimen, with especially encouraging survival for LD patients.

PMID- 8270989
TI  - Phase I/II and pharmacologic study of long-term continuous infusion etoposide
      combined with cisplatin in patients with advanced non-small-cell lung cancer.
AB  - PURPOSE: The primary objective of this study was to determine the
      pharmacodynamics of prolonged administration of low-dose etoposide by continuous
      infusion (CI). We investigated the hypothesis that maintenance of an etoposide
      concentration of 1 microgram/mL would be cytotoxic in non-small-cell lung cancer
      (NSCLC). PATIENTS AND METHODS: Thirty patients with advanced NSCLC without prior
      chemotherapy or radiotherapy were treated with etoposide at 20, 25, or 30 mg/m2/d
      infused continuously for 14 days (336 hours), following a 10-mg/m2 bolus. They
      also received cisplatin 30 mg/m2 on chemotherapy days 1, 2, and 3. Plasma
      concentrations of etoposide were measured by high-performance liquid
      chromatography at 0, 2, 4, 24, 48, 120, 336, and 342 hours after initiation of CI
      etoposide. RESULTS: The maximum-tolerated dose (MTD) of etoposide was 25 mg/m2/d
      with leukocytopenia as the dose-limiting toxicity. Plasma concentrations of
      etoposide at steady-state (Css) showed approximately twofold interpatient
      variability at each dose level, and were greater than 1 microgram/mL in most
      patients at higher dose levels. The severity of neutropenia was dependent on
      performance status (PS), age, and the Css of etoposide. The overall response rate
      for the 29 assessable cases was 28%. Five of 11 patients with a Css greater than
      1.2 micrograms/mL responded to the therapy, whereas only one of 10 patients with
      a Css less than 1 microgram/mL responded. CONCLUSION: With long-term CI of
      etoposide, a Css greater than 1 or 1.2 micrograms/mL appeared necessary, but not
      sufficient, to achieve a major response against NSCLC.

PMID- 8270990
TI  - Phase I trial of subcutaneous recombinant macrophage colony-stimulating factor:
      clinical and immunomodulatory effects.
AB  - PURPOSE: Recombinant human macrophage colony-stimulating factor (rM-CSF) has been
      demonstrated to control the growth, differentiation, and function of mononuclear
      phagocytes. Preclinical studies have indicated antitumor effects, and therefore a
      phase I trial of rM-CSF in patients with malignancy was initiated. The toxicity
      and hematologic and immunologic effects were investigated. PATIENTS AND METHODS:
      rM-CSF was administered as a subcutaneous injection on days 1 through 5 and 8
      through 12. Cycles were repeated every 28 days. Cohorts of four to seven patients
      received rM-CSF at dose levels from 0.1 to 25.6 mg/m2/d. Forty-two patients
      received 88 cycles of rM-CSF. All patients had metastatic solid tumors refractory
      to standard therapy. RESULTS: The toxicity of rM-CSF was mild. Dose-limiting
      toxicity included thrombocytopenia (two patients) and iritis (one patient)
      occurring at a dose of 25.6 mg/m2/d. Hematologic studies demonstrated dose
      related monocytosis occurring routinely at doses > or = 3.2 mg/m2/d, and
      thrombocytopenia. Immunologic studies demonstrated enhanced secretion of tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) by monocytes
      after in vitro stimulation with lipopolysaccharide, and increased expression of
      TNF-alpha mRNA at higher rM-CSF dose levels. Pharmacokinetic studies demonstrated
      that the systemic clearance rate of M-CSF increases during week 1 of therapy,
      resulting in lower blood levels of M-CSF during the second week of therapy.
      CONCLUSION: rM-CSF can be safely administered to patients, and has biologic
      activity on peripheral-blood monocytes.

PMID- 8270991
TI  - Father-daughter relationship revisited.

PMID- 8270992
TI  - A survey of expanded duties usage in Indiana: a pilot study.
AB  - PURPOSE: The information presented in this pilot study was obtained as part of a
      1990 survey of Indiana dentists. This portion of the study determined the number
      and types of expanded duties delegated to dental hygienists and the relationship
      of this information to their employer's year of graduation. METHODS: A 10% random
      sample of Indiana dentists was sent a questionnaire that asked each
      practitioner's specialty and year of graduation from dental school. In addition,
      the number of dental hygienists and assistants employed in the practice and the
      frequency of selected expanded function procedures they performed were
      determined. Statistical treatment of the survey data was accomplished by
      frequency tabulations on procedures delegated; principal component analysis
      applied to a select number of measures; and Student's t-test to variables related
      to office environment (total years experience, total staff, percentage employing
      dental hygienists, percentage employing full-time dental hygienists, number of
      procedures employed, and graduation year of dentist). The level of significance
      selected for the t-test analysis was .05. RESULTS AND CONCLUSIONS: Seventy-four
      questionnaires were returned out of 231 mailed (32% response rate). Of the
      expanded functions listed on the survey, the procedures most widely delegated to
      dental hygienists were amalgam polishing and sealant placement. The placement of
      resin and amalgam restorations was rarely performed by dental hygienists. Based
      on a principal component analysis, two office environments were defined. Type A
      offices had dentists with a mean graduation date of 1965.9. Type B offices had
      dentists with a mean graduation date of 1977.8, significantly larger staff sizes,
      and employed a higher percentage of full-time dental hygienists. Moreover, dental
      hygienists employed in Type B offices also performed a greater number of expanded
      function procedures than did dental hygienists in Type A offices.

PMID- 8270993
TI  - Musculoskeletal complaints in dental hygiene: a survey study from a Swedish
      county.
AB  - PURPOSE: Musculoskeletal complaints in dental hygienists all employed by the
      National Dental Service in a Swedish county were evaluated with a standardized
      questionnaire. METHODS: During an ergonomics course, a questionnaire similar to
      standardized Nordic questionnaires was completed by all 28 participants. The
      questionnaire elicited demographic data and the presence and location of
      musculoskeletal complaints. Standard descriptive statistical methods were used to
      analyze the data. RESULTS: Subjects were all women, with a mean age of 40 years
      and a mean time of employment of five years. Most respondents worked part-time
      (mean 80%). Neck and shoulder complaints showed a clear predominance over other
      locations. Sixty-two percent of the subjects reported complaints associated with
      the neck and 81% with one or both shoulders during the previous 12 months. The
      frequency of complaints was higher on the right side. CONCLUSIONS: Most neck,
      shoulder, arm, and back complaints were considered work-related according to the
      dental hygienists themselves. The frequency of lower extremity complaints was
      low, and only a few of these complaints were considered work-related.

PMID- 8270994
TI  - Ergonomic evaluation and construction of a reference workplace in dental hygiene:
      a case study.
AB  - PURPOSE: In an earlier survey study, a high frequency of complaints from the neck
      and shoulder were found in dental hygienists employed by the National Dental
      Service in Jonkoping, Sweden. As a consequence of these survey findings, a new in
      depth study of the workplace of one Swedish dental hygienist was performed to
      identify critical factors causing work-related pain in the neck and shoulders.
      This also served as a pilot study for testing simple ergonomic methods suitable
      for field studies in dental hygiene. METHODS: Several workplace evaluation
      methods were used: time distribution study, posture targeting diagrams,
      biomechanical computations, serial photography, and videorecording. RESULTS: All
      methods showed the same general picture--fixed working postures, a sparse
      movement pattern, work within a very limited work space, and long-standing static
      load on the neck and shoulder muscles. CONCLUSIONS: As a result of these
      findings, a reference workplace was designed to provide an ergonomically
      desirable environment. The load was reduced by means of a specific horseshoe
      shaped support for the patient chair and a special armrest for the operator
      chair.

PMID- 8270995
TI  - A short-term, three-year epidemiological study of median nerve sensitivity in
      practicing dental hygienists.
AB  - PURPOSE: Hand-intensive, repetitive motion procedures such as those performed by
      dental hygienists can lead to median nerve dysfunction which, left untreated, can
      degenerate into clinical carpal tunnel syndrome (CTS). Vibrometry has been used
      as a method for early detection of sensory nerve impairment. METHODS: A cohort of
      16 university-educated dental hygienists was evaluated by means of programmed
      frequency stimuli for median nerve dysfunction at graduation and at one, two, and
      three years postgraduation. RESULTS: The results indicate that median nerve
      dysfunction was not detected in this cohort. However, further analysis suggests
      that a significant loss of median nerve sensitivity, or permanent "threshold
      shift," has occurred in the three years since graduation. CONCLUSION: Whether
      this is a harbinger of future events is unknown at this time.

PMID- 8270996
TI  - Subgingival irrigation instruction and utilization in dental hygiene curricula.
AB  - PURPOSE: The purpose of this study was to assess subgingival irrigation
      instruction in accredited dental hygiene programs in the United States;
      specifically, the number of programs providing instruction; teaching methods
      used; delivery systems taught didactically and/or clinically; the amount of
      student clinical experience provided; clinical patient selection criteria; and
      specific irrigation solutions used. METHODS: A 17-item questionnaire was mailed
      in January 1989 to 197 accredited dental hygiene programs. Frequency
      distributions were used to describe the data. RESULTS: A response rate of 85% (N
      = 167) was obtained after two mailings. One hundred twenty-four dental hygiene
      programs (74%) provide subgingival irrigation information in their curriculum.
      Data revealed that although student experiences with subgingival irrigation
      delivery agents and systems vary greatly, a majority of schools teach the
      utilization of chlorhexidine delivered via motorized irrigation systems. Students
      who provide subgingival irrigation usually do so in selected areas for specific
      patients. CONCLUSIONS: Results from the survey indicate that a majority of dental
      hygiene programs provide some form of subgingival irrigation instruction,
      although educational content, experience, and placement of instruction within the
      two-year curricula varied. Based on these findings, dental hygiene educators may
      elect to develop standards for teaching subgingival irrigation in their programs.

PMID- 8270997
TI  - Delayed induction of mild hypothermia to reduce infarct volume after temporary
      middle cerebral artery occlusion in rats.
AB  - Deep to moderate hypothermia (24 degrees to 30 degrees C) during focal cerebral
      ischemia reduces infarct volume but must be initiated before the onset of
      ischemia to be effective and has deleterious pulmonary, myocardial and
      neurological effects. It is not known whether mild hypothermia (32 degrees to 33
      degrees C) protects against ischemic neuronal damage, whether hypothermia induced
      after the onset of ischemia has protective effects, or whether these effects are
      associated with alterations in cortical blood flow. In this study, mild whole
      body hypothermia was induced in rats just before or 10, 30, or 60 minutes after
      the onset of 2 hours of temporary middle cerebral artery occlusion; rewarming
      began immediately after reversal of occlusion and normothermia was maintained
      throughout 22 hours of reperfusion. Infarct volume, measured 24 hours after the
      end of reperfusion, was significantly smaller in rats made hypothermic within 30
      minutes after the onset of ischemia than in normothermic controls; hypothermia
      induced at 60 minutes of ischemia did not reduce infarct volume. Cortical blood
      flow, measured by laser Doppler ultrasound flowmetry, was not significantly
      different between groups during ischemia; however, postischemic cortical blood
      flow correlated positively with total infarct volume. These results indicate that
      mild hypothermia initiated during temporary focal ischemia in rats can reduce
      infarct volume without attenuating the reduction in cortical blood flow.

PMID- 8270998
TI  - The relationship between traumatic brain injury-induced changes in brain
      temperature and behavioral and anatomical outcome.
AB  - Alteration of brain temperature, experimentally induced or spontaneous, has been
      shown to affect the symptoms resulting from a variety of cerebral insults. This
      study examined the effect of traumatic brain injury (TBI) on brain and body
      temperature in rats and the relationship between TBI-induced temperature changes,
      neuropathology, and behavioral recovery. Anesthesia, surgery and TBI all caused
      changes in brain and body temperatures. The level of brain (but not body)
      temperature at the time of TBI was positively correlated with the severity of
      hippocampal and thalamic pathology. In contrast, the measured levels of both
      brain and body temperatures after TBI were not related to behavioral or
      neuroanatomical outcome. Interestingly, the increase in brain (but not body)
      temperature from the time of TBI to 5 to 10 minutes after termination of
      anesthesia was negatively correlated with behavioral and anatomical outcome.
      Simply stated, the more rapidly brain temperature returned toward normal, the
      better the rats' behavioral and anatomical outcome. This rate of return toward
      normal brain temperature is not interpreted as causally related to outcome but
      rather as an index of the severity of brain injury.

PMID- 8270999
TI  - Experimental model of posttraumatic syringomyelia: the role of adhesive
      arachnoiditis in syrinx formation.
AB  - An experimental model was devised to elucidate the role of spinal blockade in
      posttraumatic syringomyelia. Thirty-eight Japanese White rabbits, each weighing
      about 3 kg, were used in this study. The animals were divided into four groups:
      in Group 1, eight animals received traumatic injury only; in Group 2, 12 animals
      received traumatic injury following injection of 100 mg kaolin suspended in 1 cc
      normal saline solution into the subarachnoid space at the site of trauma; in
      Group 3, nine animals received traumatic injury following injection of 200 mg
      kaolin in 1 cc normal saline solution into the subarachnoid space at the site of
      trauma; and in Group 4, nine animals without traumatic injury received an
      injection of 200 mg kaolin in 1 cc normal saline solution into the subarachnoid
      space. The subjective criteria for syrinx formation were the presence of a
      definite round cyst having a smooth margin and an upper or lower extension of
      more than 2 cm from the injured site. Syrinx formation was seen in 12.5% (one of
      eight rabbits) in Group 1, 41.7% (five of 12 animals) in Group 2, 55.5% (five of
      nine rabbits) in Group 3 and 0% (none of nine animals) in Group 4 (p < 0.05).
      There was a tendency for the combined trauma/kaolin injection groups to be more
      prone to develop a syrinx. In the kaolin injection only group (Group 4), no
      animal showed a definite cyst or an extending cavity during the experimental
      period. The results suggest that kaolin enhances the extension of multiple small
      cavities that have already formed at the time of initial injury. The difference
      between the frequency of syrinx formation and the time of survival was
      statistically significant well beyond the 0.05% level. The overall difference,
      relating to the frequency of syrinx development, group, and duration of survival,
      was also statistically significant. In summary, subarachnoid block secondary to
      adhesive arachnoiditis is important in initiating the extension of the
      syringomyelia cavity.

PMID- 8271000
TI  - Coccidioidomycotic brain abscess. Case report.
AB  - Coccidioidomycosis is an infection originating in the San Joaquim Valley of
      southern California, but now seen with increasing frequency throughout southern
      California and the southwestern United States. Central nervous system involvement
      is usually manifested as meningitis. The authors present the case of a young man
      with pulmonary coccidioidomycosis who developed a brain lesion that proved to be
      a coccidioidomycotic abscess. With the increasing incidence of the disease, this
      manifestation may be encountered more often and should therefore be included in
      the differential diagnosis of any patient from an endemic area who presents with
      a brain mass.

PMID- 8271001
TI  - Low clinical ischemic threshold for cerebral blood flow in severe acute brain
      trauma. Case report.
AB  - A case of severe acute brain trauma is presented in which the patient made a
      satisfactory recovery after suffering a marked reduction in cerebral blood flow,
      to a level previously reported in association with impending brain death (10
      ml/100 gm/min). This is believed to be the first report of a patient with severe
      acute brain injury in whom serial clinical and physiological assessments allowed
      documentation of the reversibility of such a critical level of cerebral
      hypoperfusion.

PMID- 8271002
TI  - Giant cell tumor of the calvaria in a child. Case report.
AB  - A giant cell tumor involving the vertex of the skull is described in a 3-year-old
      child with no history of head trauma. The mass was present approximately 4 months
      prior to resection. Microscopically, the lesion consisted of highly cellular
      tissue composed of oval to spindle-shaped stromal cells admixed with numerous
      multinucleated giant cells. Giant cell tumor of the skull is a rare lesion,
      usually involving the sphenoid or temporal bone in adults. The differential
      diagnosis is discussed with reference to the literature regarding giant cell
      lesions, especially of the cranium. The authors are unaware of previous reports
      of a similar lesion in this location in such a young child.

PMID- 8271003
TI  - Mobile sediment of CaCO3 grains inside the cyst of an intraventricular teratoma.
      Case report.
AB  - The case of a 40-year-old woman with a mature cystic teratoma in the lateral
      ventricle is reported. An unusual mobile sediment of radiopaque material in the
      cyst was identified as grains of calcium carbonate. It was considered to have
      precipitated from the cystic fluid under specific chemical conditions.

PMID- 8271004
TI  - Improved visualization of the foramen ovale for percutaneous approaches to the
      gasserian ganglion. Technical note.
AB  - Percutaneous procedures for treating trigeminal neuralgia involve the penetration
      of foramen ovale using cutaneous landmarks and radiological guidance. The
      placement of radiopaque markers over the commonly used "zygomatic points" in
      front of the ears provides landmarks on intraoperative radiological studies that
      facilitate localization of the foramen ovale. Speed and safety of percutaneous
      trigeminal procedures should be enhanced. There is no increase in radiation
      exposure over that in other commonly used approaches.

PMID- 8271005
TI  - The surgical technique of anterior cervical fusion using bone grafts obtained
      from cervical vertebral bodies.
AB  - The authors describe the surgical technique of anterior cervical fusion using
      bone grafts obtained from cervical vertebral bodies. This series consisted of 90
      patients with cervical intervertebral disc disease suffering from cervical
      spondylotic myelopathy. Thirty-five patients were operated on at one level, 33 at
      two levels, and 22 at three levels. Postoperative x-ray films showed solid bone
      fusion in all patients at a mean follow-up time of 24 months (range 1 year to 3
      years 6 months). Anterior angulation was found in four (4.4%) of the 90 patients.
      This surgical procedure has two major advantages: 1) there are no complications
      related to the iliac donor site, allowing early patient mobilization; and 2) the
      extensive posterior spur can be removed safely and easily under a wide operative
      field without damaging the spinal cord and nerve roots.

PMID- 8271006
TI  - The Journal of Neurosurgery. Its origin and development. 1964.

PMID- 8271007
TI  - Glioblastoma multiforme and the cellular telephone scare.

PMID- 8271008
TI  - Radiosurgery and venous malformations.

PMID- 8271009
TI  - Radiosurgery and venous malformations.

PMID- 8271010
TI  - Radiosurgery and venous malformations.

PMID- 8271011
TI  - Radiation-induced meningiomas.

PMID- 8271012
TI  - Arteriovenous fistulas.

PMID- 8271013
TI  - Neurenteric cyst or teratomatous cyst.

PMID- 8271014
TI  - Neurenteric cyst or teratomatous cyst.

PMID- 8271015
TI  - Near-infrared spectroscopy.

PMID- 8271016
TI  - Focal brain-stem astrocytomas causing symptoms of involvement of the facial nerve
      nucleus: long-term survival in six pediatric cases.
AB  - Six children with a history of isolated facial nerve dysfunction or dizziness and
      nausea were treated for brain-stem glioma between 1984 and 1992. Computerized
      tomography and/or magnetic resonance (MR) imaging showed a focal, uniformly
      enhancing mass involving the facial nerve nucleus of the pons. All patients
      underwent biopsy; the histological diagnosis was juvenile pilocytic astrocytoma
      in five cases. In the remaining case the biopsy was nondiagnostic, although the
      surgeon believed that the lesion was a glioma. Postoperatively, five patients
      underwent conventional focal megavoltage radiation therapy (180 to 200 cGy/day)
      over a period of 5 1/2 weeks to a total dose of approximately 5400 cGy. One
      child's family refused radiation therapy; she remained well and stable for 4
      years, despite persistent facial weakness, and was eventually lost to follow-up
      review. Four irradiation-treated patients had complete resolution of their tumors
      on MR images and have had no evidence of neuropsychological or
      neuroendocrinological deficits during 4 1/2 to 8 years of follow-up evaluation.
      Patients whose neuroradiological studies show a lesion resembling those in this
      series should undergo biopsy and, if the histology of a low-grade tumor (in
      particular, a juvenile pilocytic astrocytoma) is confirmed, should then receive
      focal radiation therapy with conventional megavoltage dosages.

PMID- 8271017
TI  - Pseudo-cerebrospinal fluid rhinorrhea.
AB  - Because of its potentially serious sequelae, cerebrospinal fluid (CSF) leakage
      following surgery for lesions of the cranial base is given immediate attention by
      neurosurgeons. Despite a multitude of approaches used to prevent its occurrence,
      CSF leakage complicates up to 30% of difficult skull-base tumor operations. The
      authors describe the cases of 11 patients who developed a syndrome, not
      previously described in the literature, termed "pseudo-CSF rhinorrhea." This
      syndrome occurs after surgery of the cranial base, usually involving dissection
      or removal of the petrous or cavernous carotid artery, the greater superficial
      petrosal nerve, and the pericarotid sympathetic plexus. It is characterized by
      nasal stuffiness and nasal hypersecretion and is sometimes accompanied by facial
      flushing. The symptoms are characteristically exacerbated by exertion or by
      elevated ambient room temperatures. Lacrimation is typically absent ipsilateral
      to the pseudo-CSF rhinorrhea. It is believed that pseudo-CSF rhinorrhea developed
      in these patients because of a relative imbalance of the regulatory autonomic
      supply of the nasal mucosa.

PMID- 8271018
TI  - Pathophysiology of syringomyelia associated with Chiari I malformation of the
      cerebellar tonsils. Implications for diagnosis and treatment.
AB  - The mechanisms previously proposed for the progression of syringomyelia
      associated with Chiari I malformation of the cerebellar tonsils are
      controversial, leave many clinical observations unexplained, and underlie the
      prevalence of different operations currently used as initial treatment. To
      explore the mechanism of syringomyelia progression in this setting, the authors
      used anatomical and dynamic (phase-contrast and phase-contrast cine) magnetic
      resonance (MR) imaging, and intraoperative ultrasonography to examine the anatomy
      and dynamics of movement of the cerebellar tonsils, the wall of the spinal cord
      surrounding the syrinx, and the movement of cerebrospinal fluid (CSF) and syrinx
      fluid at rest, during the respiratory and cardiac cycles, and during Valsalva
      maneuver in seven affected patients. In all patients the cerebellar tonsils
      occluded the subarachnoid space at the level of the foramen magnum. Syringomyelia
      extended from the cervical to the lower thoracic segment of the spinal cord. No
      patient had evidence of a patent communication between the fourth ventricle and
      the syrinx on anatomical MR images, dynamic MR images, or intraoperative
      ultrasound studies. Dynamic MR images of three patients revealed abrupt downward
      movement of the spinal CSF and the syrinx fluid during systole and upward
      movement during diastole, but limited movement of CSF across the foramen magnum
      during the cardiac cycle. Intraoperative ultrasound studies demonstrated abrupt
      downward movement of the cerebellar tonsils during systole that was synchronous
      with sudden constriction of the spinal cord and syrinx. Decompression of the
      foramen magnum was achieved via suboccipital craniectomy, laminectomy of C-1 and
      C-2, and dural grafting, leaving the arachnoid intact. Immediately after surgery,
      the pulsatile downward thrust of the tonsils and constriction of the spinal cord
      and syrinx disappeared. Syringomyelia resolved within 1 to 6 months after surgery
      in all patients. Observations by the authors suggest the following previously
      unrecognized mechanism for progression of syringomyelia associated with occlusion
      of the subarachnoid space at the foramen magnum. The brain expands as it fills
      with blood during systole, imparting a systolic pressure wave to the intracranial
      CSF that is accommodated in normal subjects by sudden movement of CSF from the
      basal cisterns to the upper portion of the spinal canal. With obstruction to
      rapid movement of CSF at the foramen magnum, the cerebellar tonsils, which plug
      the subarachnoid space posteriorly, move downward with each systolic pulse,
      acting as a piston on the partially isolated spinal CSF and producing a systolic
      pressure wave in the spinal CSF that acts on the surface of the spinal
      cord.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271019
TI  - Platelet-activating factor (PAF) concentration and PAF acetylhydrolase activity
      in cerebrospinal fluid of patients with subarachnoid hemorrhage.
AB  - The authors studied the sequential changes in platelet-activating factor (PAF)
      and PAF acetylhydrolase in the cerebrospinal fluid (CSF) of patients with
      subarachnoid hemorrhage (SAH). Levels of PAF in CSF showed a gradual increase
      after the onset of SAH, with a subsequent decrease. The PAF concentration between
      5 and 9 days after SAH was greater in patients with cerebral infarction due to
      vasospasm than in patients without infarction. Conversely, PAF acetylhydrolase
      activity decreased gradually after SAH, then increased. The enzyme activity for
      the same period was smaller in patients with cerebral infarction than in patients
      without infarction. The distribution of the days of maximum PAF concentration and
      minimum PAF acetylhydrolase activity did not differ significantly between the two
      groups. The CSF as a source of PAF acetylhydrolase activity gave an apparent
      Michaelis constant value of 90.8 microM and a maximum velocity of 0.2
      nmol/min/mg. The optimum pH level for the PAF acetylhydrolase activity obtained
      from CSF was 6.5. The enzyme activity of CSF increased, depending on the
      incubation temperature, ranging from 25 degrees to 45 degrees C. Ethylene-glycol
      tetra-acetic acid (1 mM) was found to inhibit PAF acetylhydrolase activity in CSF
      obtained from patients with SAH. Unaltered PAF acetylhydrolase activity was
      inhibited by adding an aliquot of CSF and minimum PAF acetylhydrolase activity
      decreased following SAH. Two peaks of inhibitory activity were detected on
      Sephacryl S-200 HR gel filtration: one was eluted in void volume and the other
      with an apparent molecular mass of 13 kD. The inhibitory activity was very labile
      and was lost completely within 3 days of incubation at 4 degrees C. The
      regulation of the PAF concentration in the CSF of SAH patients is discussed.

PMID- 8271020
TI  - Early repeat surgery for persistent Cushing's disease.
AB  - The potential efficacy of early repeat transsphenoidal surgery for persistent
      Cushing's disease has not previously been examined. On 222 patients with no prior
      pituitary treatment and a preoperative diagnosis of Cushing's disease, 29 (13%)
      remained hypercortisolemic after an initial transsphenoidal pituitary
      exploration. Seventeen of these 29 patients underwent further surgery 7 to 46
      days after the initial transsphenoidal approach in order to completely excise
      suspected residual tumor. Patients were followed for 4 to 84 months (mean +/-
      standard deviation, 34 +/- 25 months) to document sustained remission or
      recurrence of Cushing's disease (a urine free cortisol level > 90 micrograms/day
      was considered evidence of recurrence). Of the 17 patients with repeat surgery,
      12 (71%) had resolution of hypercortisolism (morning plasma cortisol level < 5
      micrograms/dl); however, in three of these 12, hypercortisolism recurred 5, 12,
      and 24 months later. In 14 patients a lesion that appeared to be a tumor was
      identified during the initial procedure or on histological examination. Of these,
      12 had immediate resolution of hypercortisolism and nine are still in remission.
      Three patients, in whom no adenoma could be identified during the initial surgery
      or an examination of the partial hypophysectomy specimen from the initial
      surgery, had persistent Cushing's syndrome after the second operation. Seven
      (41%) of the 17 patients developed hypopituitarism requiring treatment with
      thyroid hormone, gonadal steroid, or vasopressin replacement. The low incidence
      of identification of an adenoma on computerized tomography or magnetic resonance
      images (three of 17 patients), the failure to find a corticotrophic adenoma
      during the initial surgery (10 of 17 patients), and the failure of these 17
      patients to respond to the initial transsphenoidal surgery suggest that they may
      comprise a subset of patients who are more difficult to treat successfully with
      surgery than most patients with Cushing's disease. Despite that, early
      reoperation induced immediate remission of hypercortisolism in 71% of cases, but
      did so at the expense of a high risk of hypopituitarism. However, since the
      alternative treatments (such as radiation therapy, long-term drug therapy, or
      bilateral adrenalectomy) also have potential adverse effects, early reoperation
      deserves consideration for the management of persistent Cushing's disease,
      especially when an adrenocorticotrophic hormone-secreting adenoma was partially
      excised during the first surgery.

PMID- 8271021
TI  - Role of intracranial pressure monitoring in severely head-injured patients
      without signs of intracranial hypertension on initial computerized tomography.
AB  - Previous studies have suggested that only a small proportion (< 15%) of comatose
      head-injured patients whose initial computerized tomography (CT) scan was normal
      or did not show a mass lesion, midline shift, or abnormal basal cisterns develop
      intracranial hypertension. The aim of the present study was to re-examine this
      finding against a background of more intensive monitoring and data acquisition.
      Eight severely head-injured patients with a Glasgow Coma Scale score of 8 or
      less, whose admission CT scan did not show a mass lesion, midline shift, or
      effaced basal cisterns, underwent minute-to-minute recordings of arterial blood
      pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP)
      derived from blood pressure minus ICP. Intracranial hypertension (ICP > or = 20
      mm Hg lasting longer than 5 minutes) was recorded in seven of the eight patients;
      in five cases the rise was pronounced in terms of both magnitude (ICP > or = 30
      mm Hg) and duration. Reduced CPP (< or = 60 mm Hg lasting longer than 5 minutes)
      was recorded in five patients. Severely head-injured (comatose) patients whose
      initial CT scan is normal or does not show a mass lesion, midline shift, or
      abnormal cisterns nevertheless remain at substantial risk of developing
      significant secondary cerebral insults due to elevated ICP and reduced CPP. The
      authors recommend continuous ICP and blood pressure monitoring with derivation of
      CPP in all comatose head-injured patients.

PMID- 8271022
TI  - Hematoma enlargement in spontaneous intracerebral hemorrhage.
AB  - In order to evaluate the incidence and risk factors of hematoma enlargement in
      spontaneous intracerebral hemorrhage (ICH), 419 cases of ICH were reviewed. The
      first computerized tomography (CT) scan was performed within 24 hours of onset
      and the second within 24 hours of admission; a blood sample was taken for
      laboratory examination within 1 hour of admission. In 60 patients (14.3%) the
      second CT scan showed an enlarged hematoma. The incidence of enlargement
      significantly decreased with time (p < 0.05) and significantly increased with the
      severity of liver dysfunction and the volume of the hematoma on the first CT
      scan. Patients with an irregularly shaped hematoma had a higher risk of hematoma
      growth than those with a round hematoma. In addition, patients with hematoma
      enlargement were more likely to have coagulation abnormalities (low platelet
      counts and low levels of fibrinogen, alpha 2-antiplasmin activity and platelet
      aggregation). Moreover, hematoma growth was associated with a poor clinical
      outcome. It is concluded that patients admitted to a hospital within 6 hours of
      onset of ICH, especially those admitted within 2 hours, and patients with liver
      dysfunction or irregularly shaped large hematomas should be closely observed for
      at least 6 hours after onset in preparation for emergency surgery, since the risk
      of hematoma growth in these circumstances is high.

PMID- 8271023
TI  - Recurrence of ICA-PCoA aneurysms after neck clipping.
AB  - Between 1975 and 1992, 2211 patients underwent aneurysmal neck clipping at the
      Nara Medical University clinic and associated hospitals. The aneurysm in 931 of
      these patients was situated at the junction of the internal carotid artery (ICA)
      and posterior communicating artery (PCoA). Seven patients were readmitted 4 to 17
      years after the first surgery because of regrowth and rupture of an ICA-PCoA
      aneurysmal sac that had arisen from the residual neck. On angiograms obtained
      following aneurysmal neck clipping, a large primitive type of PCoA was
      demonstrated in six patients and a small PCoA in one. A small residual aneurysm
      was confirmed in only two patients and angiographically complete neck clipping in
      five. Recurrent ICA-PCoA aneurysms were separated into two types based on the
      position of the old clip in relation to the new growth. Type 1 aneurysms regrow
      from the entire neck and balloon eccentrically. In this type, it is possible to
      apply the clip at the neck as in conventional clipping for a ruptured aneurysm.
      Type 2 includes aneurysms in which the proximal portion of a previous clip is
      situated at the corner of the ICA and aneurysmal neck and the distal portion on
      the enlarged dome of the aneurysm, because the sac is regrowing from a portion of
      the residual neck. In this type of aneurysm, a Sugita fenestrated clip can
      occlude the residual neck, overriding the old clip. Classifying these aneurysms
      into two groups is very useful from a surgical point of view because it is
      possible to apply a new clip without removing the old clip, which was found to be
      adherent to surrounding tissue.

PMID- 8271024
TI  - Surgical management of cavernous malformations of the third ventricle.
AB  - In order to determine adequate therapeutic approaches for cavernous malformations
      of the third ventricle, the authors reviewed a series of five such malformations
      managed at their institution and nine others reported in the literature. Four
      subgroups were identified in terms of the site of origin and could be
      characterized by different clinical manifestations: visual field defects and
      endocrine function deficits in patients with malformations in the suprachiasmatic
      region (six cases); symptoms caused by hydrocephalus in those with malformations
      in the foramen of Monro region (five cases); and deficits of short-term memory in
      those with malformations in the lateral wall (two cases) or of the floor of the
      third ventricle (one case). Unlike cavernous malformations at other locations,
      malformations of the third ventricle frequently demonstrated rapid growth (43%)
      and mass effects (71%). The surgical or autopsy findings suggested that the
      growth was attributable to repeated intralesional hemorrhages. Extralesional
      hemorrhage was also not uncommon, occurring in 29% of patients. Such tendencies
      require the adoption of a more aggressive approach to this particular group of
      cavernous malformations as compared to those in other locations. The risks of
      regrowth and extralesional hemorrhage appear to be reduced only by complete
      excision. The surgical approaches adopted should be aimed at providing the best
      access to the site where the malformation has arisen. The translamina terminalis
      approach for cavernous malformations in the suprachiasmatic region, the
      transventricular or transcallosal interfornicial approaches for those in the
      foramen of Monro region and the transvelum interpositum approach for those in the
      lateral wall or the floor of the third ventricle appear to be appropriate. In
      order to select the adequate surgical approach, precise diagnosis of the site of
      origin is crucial. In addition to neuroimaging techniques, the patient's initial
      symptoms provide valuable information.

PMID- 8271025
TI  - Intraoperative angiography in the resection of arteriovenous malformations.
AB  - Surgical resection of 13 operatively obscure arteriovenous malformations (AVM's)
      was accomplished with the assistance of intraoperative angiography, which was
      performed stereographically to provide three-dimensional orientation and was
      repeated until total resection of the AVM was confirmed. All films obtained were
      subtracted to improve clarity. The method presented here may be useful for the
      resection of all types of AVM. Only two patients had residual AVM after the
      initial operation. No complications attributable to angiography were noted.

PMID- 8271026
TI  - DNA index and S-phase in primary brain tumors. A comparison between fresh and
      deparaffinized specimens studied by flow cytometry.
AB  - Forty-nine primary intracranial tumors (33 astrocytomas, eight acoustic
      schwannomas, five oligodendrogliomas, and three miscellaneous tumors) were
      studied by flow cytometry. Each tumor specimen was divided into two portions: one
      was studied as an unfixed suspension stained with propidium iodide and the other
      after formalin fixation and paraffin embedding. The 50-microns sections from the
      paraffin blocks were deparaffinized, rehydrated, and enzymatically disintegrated,
      and the cells in suspension were stained with propidium iodide. Flow cytometry of
      the two portions showed a significant correlation between fresh and fixed
      specimens regarding the S-phase (r = 0.87) and a very close correlation fo the
      deoxyribonucleic acid (DNA) index (r = 0.95). When the 33 astrocytomas were
      analyzed separately, similar results were obtained (r = 0.86 for S-phase and r =
      0.93 for DNA index, respectively). This study demonstrated a high correlation
      between fresh and fixed specimens for DNA ploidy and S-phase both in primary
      intracranial tumors in general and also in the selected subgroup of astrocytomas.

PMID- 8271027
TI  - Generation of cytotoxic immune responses during the progression of a rat glioma.
AB  - Cytotoxic T lymphocytes specific for tumor-associated antigens are produced by
      exposing animals to tumor cells and stimulating lymphocytes from animals
      immunized in vitro with tumor cells and small amounts of interleukin-2 (IL-2).
      This study was designed to determine whether a fast-growing immunogenic avian
      sarcoma virus-induced glioma produces primed cytotoxic T lymphocyte precursors
      during its progression. Lymphocytes from intracerebral glioma-bearing rats
      generally failed to proliferate in vitro in response to immunization with tumor
      cells and IL-2 and, when proliferative responses were observed, the lymphocytes
      were not cytotoxic for glioma cells. However, when the same tumor was growing
      subcutaneously, lymphocytes proliferated and exhibited glioma-specific
      cytotoxicity when stimulated in vitro with autologous tumor cells and IL-2.
      Subcutaneous immunization of intracerebral glioma-bearing rats with tumor cells
      and adjuvant induced strong cytotoxic T lymphocyte responses. The results
      demonstrated that, while intracerebral tumor progression itself does not induce
      an anti-glioma immune response, immune responses to tumor-associated antigens may
      be induced by systemic immunization of tumor-bearing animals. The results suggest
      that the immunogenicity of brain tumors is masked by the immunologically
      privileged status of the brain, not by the induction of generalized immune
      suppression during tumor progression.

PMID- 8271028
TI  - The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord
      injury in rats.
AB  - Recent clinical trials have reported that methylprednisolone sodium succinate
      (MP) or the monosialic ganglioside GM1 improves neurological recovery in human
      spinal cord injury. Because GM1 may have additive or synergistic effects when
      used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat
      spinal cord contusion model. Spinal cord injury was caused by dropping a rod
      weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at
      T-10, which had been exposed via laminectomy. The lesion volumes were quantified
      from spinal cord Na and K shifts at 24 hours after injury and the results were
      verified histologically in separate experiments. A single dose of MP (30 mg/kg),
      given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56%
      (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity
      groups, respectively, compared to similarly injured control groups treated with
      vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and
      increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to
      30 mg/kg) had little or no effect on any measured variable compared to vehicle
      controls; when given concomitantly with MP, GM1 blocked the neuroprotective
      effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced
      reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked
      these effects of MP. The effects of MP on injury-induced hyponatremia and body
      weight loss were also blocked by GM1. Thus, GM1 antagonized both central and
      peripheral effects of MP in spine-injured rats. Until this interaction is
      clarified, the authors recommend that MP and GM1 not be used concomitantly to
      treat acute human spinal cord injury. Because GM1 modulates protein kinase
      activity, protein kinases inhibit lipocortins, and lipocortins mediate anti
      inflammatory effects of glucocorticoids, it is proposed that the neuroprotective
      effects of MP are partially due to anti-inflammatory effects and that GM1
      antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial
      effects of GM1 reported in central nervous system injury may be related to the
      effects on neural recovery rather than acute injury processes.

PMID- 8271029
TI  - Altered cerebral energy metabolism in Alzheimer's disease: a PET study.
AB  - In an effort to better understand the metabolic basis for the reported decreases
      in regional cerebral cortex glucose metabolism in patients with Alzheimer's
      disease, glucose utilization oxygen consumption and regional cerebral blood flow
      were examined. METHODS: Nine patients with Alzheimer's disease and nine age
      matched normal controls were imaged using 18F-labeled deoxyglucose and 15O
      labeled gases. RESULTS: Regional analysis of the cerebral metabolic rate of
      glucose (CMRglu), cerebral metabolic rate of oxygen (CMRO2) and cerebral blood
      flow (CBF) revealed that these values were significantly low in the frontal,
      parietal and temporal regions. The parietotemporal region had an abnormally high
      metabolic ratio (CMRO2/CMRglu), while the frontal, sensorimotor and occipital
      visual cortices had a metabolic ratio similar to that of the normal controls.
      CONCLUSIONS: These findings suggest that the abnormal parietotemporal metabolism
      in Alzheimer's disease involves a metabolic shift from glycolytic to oxidative
      metabolism. This impairment of glucose degradation may be the basis for synoptic
      dysfunction underlying the impairment observed in Alzheimer's disease.

PMID- 8271030
TI  - Microautoradiographic study for the differentiation of intratumoral macrophages,
      granulation tissues and cancer cells by the dynamics of fluorine-18
      fluorodeoxyglucose uptake.
AB  - A substantial amount of macrophage infiltration occurs in both human and animal
      tumors. We previously showed that 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG)
      uptake was higher in tumor-associated macrophages and young granulation tissues
      than in tumor cells. Differentiation of intratumoral non-neoplastic cells from
      neoplastic cells is important not only for the reduction of false-positives in
      FDG-PET tumor studies but also for patient management. METHODS: A time-course
      study was performed using micro- and macro-autoradiography and tissue
      distribution in C3H/He mice bearing transplanted syngeneic FM3A mammary carcinoma
      and MH134 hepatoma was evaluated to analyze the intratumoral cellular dynamics of
      [18F]FDG and 2-deoxy-D-[3H]glucose in vivo. RESULTS: The volume-doubling time in
      vivo was 1.3 days for MH134 and 4.9 days for FM3A, and the survival time of the
      host was 32.1 and 40.3 days, respectively. The peak uptake of both tracers in the
      tumor was 60 min after intravenous injection. The uptake by MH134 was 1.7-2.1
      times higher than that by FM3A. The intracellular concentration as determined by
      counting the silver grains on micro-autoradiographic sections showed that the
      uptake by macrophages and focal small necrotic areas in both tumors was faster
      than the blood clearance until 15 min after tracer injection. CONCLUSION: Thus,
      non-neoplastic cellular elements can be differentiated from viable neoplastic
      cells by means of the dynamic analysis of [18F]FDG uptake.

PMID- 8271031
TI  - The influence of tracer localization on the electron dose rate delivered to the
      cell nucleus.
AB  - The radiation dose rate delivered by electron emissions of 99mTc, 123I, 111In,
      67Ga and 201Tl was evaluated at the subcellular level. METHODS: Spherical models
      of sources were used to simulate various cellular localizations of radionuclides.
      These models were applied to large lymphocytes, assuming uniform distributions of
      radioactivity throughout the nucleus, the cytoplasm or the cell membrane surface.
      RESULTS: The graphs of the absorbed dose rate plotted according to the distance
      from the center of the cell show that the dose rate strongly depends on the
      subcellular distribution of the radioisotope. The absorbed dose rate D(0) at the
      center of the cell delivered by a constant cellular radioactivity of 99mTc, 123I,
      111In, 67Ga and 201Tl is respectively 94, 21, 18, 74 and 76 times higher if the
      radioactivity is localized within the cell nucleus than if it is situated only on
      the cell membrane. D(0) for subcellular localizations was compared to D(0)
      obtained by assuming uniform distribution of radioactivity throughout the cell.
      This latter assumption may underestimate the dose rate from 2.8- to 3.2-fold if
      the tracer is exclusively localized within the nucleus or overestimate from 4.3-
      to 30-fold if the tracer is localized within the cytoplasm or on the cell
      membrane, depending on the radionuclide. CONCLUSION: Such findings show that the
      localization of radiopharmaceuticals at the subcellular level plays a crucial
      role in determining the actual dose delivered to the cell nucleus in diagnostic
      nuclear medicine procedures.

PMID- 8271032
TI  - NBTF hopefuls scramble for DOE grant.

PMID- 8271033
TI  - Investigations of ascorbate for direct labeling of antibodies with technetium
      99m.
AB  - Recently, a method for the direct labeling of antibodies with 99mTc was described
      in which sulfhydryls were reportedly generated by reduction of antibody
      disulfides with ascorbic acid. Thereafter, these proteins may be labeled at high
      efficiency with 99mTc following reduction of pertechnetate with dithionite. This
      investigation was initially conducted to evaluate the mechanism of the increased
      stability towards cysteine challenge reported for the label and subsequently to
      determine the role of ascorbate in the labeling process. METHODS: It was possible
      to reproduce the reported high labeling efficiencies by increasing the dithionite
      concentration fivefold, presumably because of variabilities among lots of
      commercial sodium dithionite. RESULTS: Despite success in labeling, it was not
      possible to confirm that antibody reduction followed the treatment with
      ascorbate. Using both Ellman's reagent and 2,2' dithiodipyridine as indicators,
      we were unable to detect sulfhydryls on one IgG antibody treated at ten times the
      suggested ascorbate-to-antibody molar ratio. It was estimated that the number of
      sulfhydryls generated could not have been more than 1% (dithiodipyridine) to 2%
      (Ellman's). Furthermore, radiolabeling efficiencies for two IgG antibodies and
      stabilities of the label to cysteine challenge were unchanged when the ascorbate
      was eliminated. The number of sulfhydryls generated by treatment of the antibody
      with dithionite at 1-2 times the concentration required for adequate labeling was
      about 1% (dithiodipyridine) to 5% (Ellman's). CONCLUSION: For the conditions of
      this investigation and for the antibodies employed, ascorbate apparently played
      no more than a minor role at best in the labeling process. If antibody reduction
      occurred, this most likely was a result of residual dithionite presented to the
      protein along with the reduced 99mTc.

PMID- 8271034
TI  - An evaluation of lesion detectability with cone-beam, fanbeam and parallel-beam
      collimation in SPECT by continuous ROC study.
AB  - To evaluate lesion detectability for clinical evaluation of cone-beam (CB),
      fanbeam (FB) and parallel-beam (PB) collimator sensitivity, experimentally
      acquired phantom data were used to assess the advantage of CB collimation over
      conventional collimation. METHODS: Lesion detectability with CB, FB and PB
      collimation in SPECT was compared using a three-dimensional brain phantom and
      continuous receiver operating characteristic (CROC) analysis. A simulated cold
      lesion was located near the posterior portion of the thalamus. High count density
      scans of this phantom were acquired with CB, FB and PB collimators with similar
      resolution. These projections were scaled to count levels which reflected the
      measured sensitivities of the three collimators. Computer-generated Poisson noise
      was added to the projections to produce uncorrelated data sets. Images were
      reconstructed using a filtered backprojection algorithm. All reconstructions used
      a Hann filter with multiplicative attenuation correction. Each of seven trained
      observers viewed 288 sets of images and indicated the certainty of perceiving a
      cold lesion at a specified location by a rating of 0-100. Each image set
      contained four adjacent slices centered on the lesion to minimize partial volume
      effects. The program LABROC4 was used to fit CROC curves to individual observers'
      ratings. A t-test for paired data was performed on the individual areas. RESULTS:
      The average areas (standard deviations) under CROC curves for CB, FB and PB were
      0.89 (0.03), 0.83 (0.05) and 0.76 (0.04), respectively. The differences of the
      areas were statistically significant with all two-tailed p values < 0.02.
      CONCLUSION: These results demonstrate that cold lesions in the posterior portion
      of the thalamus are best detected by images obtained using CB followed by FB and
      PB collimation.

PMID- 8271035
TI  - Clinical cone-beam SPECT.

PMID- 8271036
TI  - Comparison of four scatter correction methods using Monte Carlo simulated source
      distributions.
AB  - Scatter correction in SPECT is important for improving image quality, boundary
      detection and the quantification of activity in different regions. This paper
      presents a comparison of four scatter correction methods, three using more than
      one energy window and one convolution-subtraction correction method using spatial
      variant scatter line-spread functions. METHODS: The comparison is based on Monte
      Carlo simulated data for point sources on- and off-axis, hot and cold spheres of
      different diameters, and a clinically realistic source distribution simulating
      brain imaging. All studies were made for a uniform cylindrical water phantom.
      Since the nature of the detected photon is known with Monte Carlo simulation,
      separate images of primary and scattered photons can be recorded. These can then
      be compared with estimated scatter and primary images obtained from the different
      scatter correction methods. The criteria for comparison were the normalized mean
      square error, scatter fraction, % recovery and image contrast. RESULTS: All
      correction methods significantly improved image quality and quantification
      compared to those obtained with no correction. Quantitatively, no single method
      was observed to be the best by all criteria for all the source distributions.
      Three of the methods were observed to perform the best by at least one of the
      criteria for one of the source distributions. For brain imaging, the differences
      between all the methods were much less than the difference between them and no
      correction at all. CONCLUSION: It is concluded that performing scatter correction
      is essential for accurate quantification, and that all four methods yield a good,
      but not perfect, scatter correction. Since it is hard to distinguish the methods
      consistently in terms of their performance, it may be that the choice should be
      made on the basis of ease of implementation.

PMID- 8271037
TI  - Absorbed fractions for electrons and beta particles in spheres of various sizes.
AB  - The use of electron-emitting radionuclides in tumor imaging and therapy has
      presented some new challenges to conventional radiation dosimetry. The fraction
      of electron energy absorbed in most source regions has usually been assumed to be
      unity. In small structures such as localized tumors or isolated regions
      containing moderate to high energy electron emitters, however, this may not
      always be the case. METHODS: Using an extension of Berger's scaled absorbed dose
      distributions for point sources to represent a spherical geometry, absorbed
      fractions of electron energy for sources uniformly distributed in spheres of
      various sizes have been calculated. RESULTS: Beta particle and monoenergetic
      electron energies studied range from 0.025 to 4.0 MeV and sphere masses range
      from 0.01 to 1000 g. S values have also been calculated for 90Y, 123I and 131I
      based on the results of the absorbed fraction calculations. CONCLUSION: These
      calculated absorbed fractions are valuable in estimating electron energy loss
      from small spherical structures and may be useful in estimating the radiation
      dose to these small volumes.

PMID- 8271038
TI  - Magnetically enhanced radionuclide therapy.
AB  - Radiopharmaceutical therapy is an increasingly common treatment for cancer. This
      therapy involves the injection of radiolabeled tumor-specific agents into the
      patient with subsequent preferential accumulation in the tumor sites. Particulate
      radiation (usually beta particles) emitted by the radioisotope kill or damage the
      tumor cells. The effectiveness of radiopharmaceutical therapy, however, is
      limited by the size of the tumor treated. Energetic particles can easily exist
      small tumors before they are able to deposit their energy and inflict significant
      damage. METHODS: We propose the use of a static magnetic field to be applied
      after the radiopharmaceutical has localized in the tumors, constraining these
      particles to helical paths. This application would result in substantially
      confining the emitted particles within the tumor's boundaries, thus increasing
      radiation dose to the tumor. RESULTS: Computer simulations of radionuclide
      treatments using 131I, 186Re and 90Y show that a magnetic field of 10 Tesla can
      increase the radiation dose achieved by conventional radionuclide therapy by up
      to 71%. In addition, total radiation dose to surrounding normal tissues is
      substantially reduced. CONCLUSION: Magnetically enhanced radionuclide therapy
      (MERiT) therefore shows promise as an effective treatment of cancer and warrants
      further study.

PMID- 8271039
TI  - Detection and comparison of patterns in images.

PMID- 8271041
TI  - Something borrowed, something blue.

PMID- 8271040
TI  - Standardized uptake values of FDG: body surface area correction is preferable to
      body weight correction.
AB  - Standardized uptake values (SUVs) are widely used to measure 18F
      fluorodeoxyglucose (FDG) uptake in various tumors. It has been reported that
      normalization of FDG uptake for patient body weight (SUVbw) overestimates FDG
      uptake in heavy patients, as their fraction of body fat (with low FDG uptake) is
      often increased. The objective of this study was to determine if "normalization
      of FDG uptake for the body surface area" (SUVbsa) is independent of the patient's
      body size and is more reliable than SUVbw. METHODS: FDG-PET images were acquired
      on 44 patients (body weight range: 45-115 kg) with cancer. SUVbw [(mCi/g of
      tissue)/(mCi injected/patient body weight in g)] and SUVbsa [(mCi/g of
      tissue)/(mCi injected/patient BSA in m2)] were determined for the liver. Since
      most observers are accustomed to using the SUVbw, the two values were compared by
      setting the mean SUVbsa equal to that of SUVbw. RESULTS: SUVbw and SUVbsa were
      3.42 +/- 0.85 (mean +/- s.d.) and 3.42 +/- 0.60, respectively. The standard
      deviation of the SUVbsa was smaller than that of SUVbw. More importantly, there
      was a strong positive correlation between SUVbw and, not only body weight (r =
      0.75) but also BSA (r = 0.68), whereas only a weak correlation between SUVbsa and
      body weight (r = 0.41) or BSA (r = 0.38) was found with a near flat regression
      line. CONCLUSION: SUVbw overestimates FDG uptake in large patients. SUVbsa
      appears preferable to SUVbw, since it is minimally affected by the body size.

PMID- 8271042
TI  - Cardiovascular nuclear medicine training guidelines. The Cardiovascular Council
      of the Society of Nuclear Medicine.

PMID- 8271043
TI  - Technetium-99m pertechnetate salivary gland imaging: its role in the diagnosis of
      Warthin's tumor.

PMID- 8271044
TI  - Quality control of radiolabeled leukocytes with monoclonal antibodies.

PMID- 8271045
TI  - Effects of erythromycin on alcohol absorption.

PMID- 8271046
TI  - Application of the effective dose equivalent to nuclear medicine patients.

PMID- 8271047
TI  - Use of the effective dose equivalent.

PMID- 8271048
TI  - Application of the effective dose equivalent to nuclear medicine patients.

PMID- 8271049
TI  - Limitations of the effective dose equivalent.

PMID- 8271050
TI  - Latex D-dimer for diagnosing pulmonary embolism.

PMID- 8271051
TI  - Negative predictive value of C-reactive protein testing.

PMID- 8271052
TI  - Wall dose estimates.

PMID- 8271053
TI  - Samarium-153-EDTMP dosimetry.

PMID- 8271054
TI  - Current status of clinical PET.

PMID- 8271055
TI  - PET studies in psychiatry: validity, accuracy and future.

PMID- 8271056
TI  - SPECT images of technetium-99m-ethyl cysteinate dimer in cerebrovascular
      diseases: comparison with other cerebral perfusion tracers and PET.
AB  - To assess the clinical role of 99mTc-ethyl cysteinate dimer (ECD) as a cerebral
      perfusion tracer, 10 patients with unilateral cerebral infarction were studied.
      METHODS: ECD SPECT images were compared with IMP and/or HMPAO SPECT in nine
      patients, seven in chronic phases and two in subacute phases. Five of these
      patients and one additional patient with chronic infarction received PET imaging
      in order to compare ECD distribution with quantitative regional cerebral blood
      flow (rCBF) and oxygen metabolism (rCMRO2) images. RESULTS: In patients with
      chronic cerebral infarction, regression analysis showed excellent correlation
      between ECD and IMP in the uptake ratio of lesions-to-nonaffected cortices (r =
      0.91). In two cases of subacute infarction, decreased uptake of ECD was observed
      in the area of "luxury perfusion," which showed elevated or preserved rCBF with
      diminished rCMRO2. On visual analysis, ECD image contrast was less prominent
      compared to that of IMP, but contrast was better than that of HMPAO. CONCLUSIONS:
      ECD uptake showed a curvilinear relationship against rCBF, suggesting flow
      limited uptake in a high flow range. ECD is a clinically useful cerebral
      perfusion tracer with distinct characteristics when compared with other available
      agents.

PMID- 8271057
TI  - Carbon dioxide reactivity by consecutive technetium-99m-HMPAO SPECT in patients
      with a chronically obstructed major cerebral artery.
AB  - In the management of major cerebral artery obstruction, cerebral perfusion
      reserve is key to introducing cerebral revascularization surgery. The purpose of
      this study was to evaluate the feasibility of assessing cerebral perfusion
      reserve by consecutive 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) SPECT
      with 5% carbon dioxide (CO2) inhalation. METHODS: The CO2 inhalation and
      consecutive 99mTc-HMPAO SPECT study was performed on 30 chronic ischemic
      cerebrovascular disease patients with unilateral major cerebral artery
      obstruction and on 27 patients without. CO2 reactivity was expressed as the
      percent increase of 99mTc-HMPAO accumulation from the baseline (%Change) and as a
      constant k' that was the ratio of 99mTc-HMPAO accumulation per 1 mmHg change of
      end-tidal CO2 tension by exponential curve fitting. RESULTS: The mean %Change and
      k' in the middle cerebral artery (MCA) territory on the side without an
      obstructive lesion or in the cerebellum ranged from 10.0% to 11.1% and from 0.98%
      to 1.13% per mmHg, respectively. In the MCA territory, an obstructive lesion was
      noted in 5.9% versus 0.54% per mmHg in the contralateral MCA territory (p <
      0.01). Eleven of 30 patients with major cerebral artery obstruction revealed
      significant asymmetry in the k' value between bilateral MCA territories.
      CONCLUSION: The results showed compromised cerebral perfusion reserve in the
      obstructed major cerebral artery territory. The present method was proven
      clinically useful for evaluating cerebral perfusion reserve in patients with
      unilateral major cerebral artery obstruction.

PMID- 8271058
TI  - Cerebral versus myocardial stress perfusion imaging: role of pharmacological
      intervention in the diagnostic assessment of flow reserve.

PMID- 8271059
TI  - Cerebral blood flow study in patients with moyamoya disease evaluated by IMP
      SPECT.
AB  - We studied the usefulness of IMP SPECT with acetazolamide in 16 patients with
      moyamoya disease. Cerebral angiography was performed for all patients who were
      classified in three grades according to their angiographic stages. METHODS:
      Techniques used included ring-type emission computed tomography with a
      minicomputer system. Patients received 111 MBq of 123I-IMP and SPECT images were
      obtained 20 min postinjection. Nine patients were studied using iodoamphetamine
      (IMP) SPECT with and without acetazolamide. IMP SPECT with acetazolamide was
      performed 20 min after each injection of 1 g of acetazolamide. RESULTS: Low
      perfusion areas in the upper and lower frontal, parietal and temporal regions in
      grades 2 and 3 using IMP SPECT were observed. The mean cerebral-to-cerebellar
      activity ratios (C/C ratio) of six regions (upper and lower frontal, temporal,
      parietal occipital and basal ganglia) in grades 1, 2 and 3 were 0.96 to 1.06,
      0.91 to 0.96 and 0.76 to 0.88, respectively. CONCLUSION: Our results indicate
      that measurement of regional cerebral blood flow (rCBF) elucidates cerebral
      hemodynamic factors, including the reactivity of cerebral vessels which cannot be
      detected angiographically in patients with moyamoya disease, and that the
      acetazolamide test is useful for detecting cerebral blood flow reserve. The test
      can be used to detect disease progress prospectively.

PMID- 8271060
TI  - Kinetics of 14(R,S)-fluorine-18-fluoro-6-thia-heptadecanoic acid in normal human
      hearts at rest, during exercise and after dipyridamole injection.
AB  - The myocardial uptake kinetics of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid
      (FTHA) were evaluated in humans with PET. The relationship between human
      myocardial FTHA uptake kinetics and the rate-pressure product (RPP) as an index
      of myocardial oxygen consumption was investigated in seven normal subjects under
      fasting conditions. METHODS: Seven studies were performed at rest and under
      submaximal continuous supine bicycle exercise with elevated RPP. An additional
      five studies were performed after dipyridamole injection to increase myocardial
      blood flow independent of the myocardial energy requirement. RESULTS: In all
      studies, rapid tracer uptake was found within 2-3 min after injection, which
      remained nearly constant during the 30-min study. Patlak plots of myocardial FTHA
      kinetics showed a linear increase, indicating metabolic trapping. The mean uptake
      rate constant, Ki, obtained from Patlak plot analysis was 0.11 +/- 0.02 ml/g/min
      at rest and increased significantly to 0.26 +/- 0.06 ml/g/min during exercise.
      The dipyridamole study yielded a comparatively small elevation with a mean Ki of
      0.15 +/- 0.02 ml/g/min, which was not significant in the analysis of variance and
      the Duncan range test. There was a significant correlation between Ki and RPP,
      with r = 0.85 (p < 0.01). CONCLUSION: Analysis of FTHA uptake kinetics with PET
      may be useful for noninvasive assessment of myocardial utilization of exogenous
      long-chain fatty acids in general and of beta oxidation in the fasting state.

PMID- 8271061
TI  - Iodine-123-Tyr-3-octreotide uptake in pancreatic endocrine tumors and in
      carcinoids in relation to hormonal inhibition by octreotide.
AB  - Uptake of 123I-Tyr-3-octreotide (TOCT) by hormone-secreting abdominal tumors was
      studied to compare scintigraphic observations with the reduction in hormone
      levels brought about by a brief therapeutic test. METHODS: A prospective study
      was conducted on 17 patients, totalizing 46 proven lesions, with endocrine tumors
      of the pancreas (10 patients, 20 lesions) and/or carcinoid metastases (8
      patients, 26 lesions). Tumor hormonal hypersecretion was inhibited by octreotide.
      RESULTS: There was good agreement between the results of these examinations.
      CONCLUSIONS: The detection of abdominal tumors using this radiotracer is strongly
      related to its functional characteristics. Variations in the scintigraphic and
      test results according to different tumor types were in agreement with published
      data on the density of somatostatin receptors measured by in vitro studies or
      scintigraphy and by the therapeutic effects of octreotide.

PMID- 8271062
TI  - Neural-network classification of normal and Alzheimer's disease subjects using
      high-resolution and low-resolution PET cameras.
AB  - Neural-network classification methods were applied to studies of FDG-PET images
      of the brain acquired from a total of 77 "probable" Alzheimer's disease and 124
      normal subjects at two different centers. METHODS: Classification performances,
      as determined by relative-operating-characteristic (ROC) analyses of cross
      validation experiments, were measured for FDG PET images obtained with either a
      15-mm FWHM PETT V or a 6-mm FWHM Scanditronix PC-1024-7B camera for various
      methods of data representation. Neural networks were trained to distinguish
      between normal and abnormal subjects on the basis of regional metabolic patterns.
      For both databases, classification performance could be improved by increasing
      the "resolution" of the representation (decreasing the region size) and by
      normalizing the regional metabolic values to the value of a reference region
      (occipital region). RESULTS: The optimal classification performance for
      Scanditronix data (ROC area = 0.95) was higher than that for PETT V data (ROC
      area = 0.87). Under Bayesian theory, the classification performance with
      Scanditronix data corresponded to an ability to change a pre-test probability of
      disease of 50% to a post-test probability of either 90% for a positive
      classification or 10% for a negative classification. CONCLUSION: This
      classification can be used to either strongly confirm or rule out the presence of
      abnormalities.

PMID- 8271063
TI  - Measuring lung shunting in hepatocellular carcinoma with intrahepatic-arterial
      technetium-99m macroaggregated albumin.
AB  - With increased use of intraarterial administration of chemotherapeutic and
      radioactive particulate agents, it is necessary to assess agent delivery in the
      lung. METHODS: Technetium-99m-labeled macroaggregated albumin (99mTc-MAA)
      delivered through the hepatic artery was used to determine the degree of lung
      shunting in 125 patients with hepatocellular carcinoma (HCC). RESULTS: The
      percentage of lung shunting varied among patients and it ranged from less than 1%
      to 67.2%, with a median of 8.1%. The degree of shunting depended on the
      vascularity of the tumors but not on the tumor size. The effect of angiotensin II
      on lung shunting was tested on six patients and there was no significant
      difference found between those patients who were pre-treated with angiotensin II
      and those who were not. One patient who underwent a liver resection, had a
      significant decrease in lung shunting from 28.5% to less than 1% after surgery.
      CONCLUSION: The lack of effect of angiotensin II together with the almost
      complete ablation of lung shunting by tumor resection suggested neoplastic blood
      vessels were responsible for the shunting.

PMID- 8271064
TI  - The efficacy of indium-111-polyclonal IgG for the detection of infection and
      inflammation.
AB  - The purpose of this study was to determine the efficacy of 111In-polyclonal
      immunoglobulin (IgG) for the diagnosis of infection or inflammation. METHODS:
      Fifty-three patients with suspected infection were prospectively studied. Each
      underwent an 111In-polyclonal IgG study; biopsy, surgery, additional nuclear
      medicine scans and radiographic studies were used to confirm the IgG scan
      results. RESULTS: The polyclonal IgG scan had a sensitivity of 97.9% and a
      specificity of 94% for infection or inflammation. When only infection or severe
      inflammation such as bowel infarction was considered, the sensitivity remained
      the same but the specificity fell to 83%. Chronic infections were detected
      equally as well as acute infections. Antibiotics, steroids, anti-inflammatory
      agents, diabetes and diminished renal function did not affect scan sensitivity.
      There were no adverse reactions to the radiopharmaceutical. Three patients
      underwent extended imaging. Their scans stayed positive for an average of 8 days.
      Three patients treated for infection had their scans turn negative on repeat
      study, confirming the efficacy of their antibiotic therapy. CONCLUSION: Indium
      111-polyclonal IgG is an effective imaging agent of infection and/or inflammation
      that is useful in a variety of infections and in severe inflammatory diseases.
      The ease of preparation and safety make it an attractive alternative to labeled
      leukocytes.

PMID- 8271065
TI  - Fractional mean transit time in transplanted kidneys studied by technetium-99m
      DTPA: comparison of clinical and biopsy findings.
AB  - To determine the usefulness of fractional mean transit time (MTT) in the
      differential diagnosis of postrenal transplant complications, 99mTc-DTPA was used
      to evaluate differences in MTT between the outer zone (cortical nephron) and
      middle zone (juxtamedullary nephron, calcyces and cortical nephron) of the
      kidney. It is well known that acute rejection is characterized by delayed
      cortical transit time, whereas cortical nephron function is well maintained and
      juxtamedullary function is impaired after renal ischemia. METHODS: Technetium-99m
      DTPA fractional MTT was determined by deconvolution analysis of 89 renograms
      obtained within 5 days of the date of kidney graft biopsy and evaluation.
      RESULTS: Outer zone MTT was significantly shorter than middle zone MTT in normals
      (2.7 +/- 0.4 versus 3.0 +/- 0.6 min, n = 22, p < 0.001), acute tubular necrosis
      (3.4 +/- 1.1 versus 3.6 +/- 1.4 min, n = 19, p < 0.01), chronic rejection (3.9 +/
      1.5 versus 5.0 +/- 2.3 min, n = 14, p < 0.001) and obstruction (4.1 +/- 0.6
      versus 8.9 +/- 3.4 min, n = 13, p < 0.001). In contrast, outer zone MTT was
      significantly longer than middle zone MTT in acute rejection (4.8 +/- 3.2 versus
      4.2 +/- 2.5 min, n = 21, p < 0.05). CONCLUSION: Fractional MTT was demonstrated
      to be useful in differentiating acute rejection and ATN in transplanted kidneys.

PMID- 8271066
TI  - EPA divided over radon risk in drinking water.

PMID- 8271067
TI  - Positron emission tomography with fluorine-18-fluorodeoxyglucose for the
      evaluation of therapeutic isolated regional limb perfusion in a patient with soft
      tissue sarcoma.
AB  - METHODS: The treatment of a patient with soft-tissue sarcoma was evaluated with
      FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of
      the left thigh was achieved with isolated regional perfusion of the limb with
      tumor necrosis factor alpha, interferon gamma and melphalan. RESULTS: PET with
      18F-FDG before perfusion showed high glucose consumption in the tumor. After
      perfusion, glucose metabolism in the tumor was absent. Subsequent excision
      confirmed complete necrosis of the tumor. CONCLUSION: FDG-PET may be useful in
      evaluating the results of isolateral regional limb perfusion for soft-tissue
      sarcomas.

PMID- 8271068
TI  - Intraperitoneal leakage of technetium-99m-DTPA following renal transplantation: a
      sign of chylous ascites.
AB  - A 7-yr-old girl developed persistent ascites following renal transplantation.
      METHODS: Renal scintigraphy periodically performed to monitor renal function of
      the transplanted kidney showed increased 99mTc-DTPA in the abdominal cavity on
      delayed imaging. RESULTS: Paracentesis demonstrated a cloudy yellow, odorless
      fluid which was identified as chylous ascites, an extremely rare complication of
      abdominal vascular surgery. CONCLUSION: Technetium-99m-DTPA in the peritoneal
      cavity following renal transplantation should be recognized as a sign suggestive
      of chylous ascites.

PMID- 8271069
TI  - Scintigraphic detection of osteomyelitis in osteopetrosis.
AB  - METHODS AND RESULTS: The diagnosis of osteomyelitis in severe osteopetrosis may
      be difficult since altered bone architecture and fractures veil the typical
      radiographic signs of inflammation. We present a case of adult osteopetrosis with
      questionable clinical and radiographic signs of two osteomyelitic foci in the
      foot. CONCLUSION: Despite severe skeletal disease, the combination of skeletal
      and leukocyte scintigraphy suggested the diagnosis of infection.

PMID- 8271070
TI  - Accumulation of 2-deoxy-2[18F]fluoro-D-glucose in human cancers
      heterotransplanted in nude mice: comparison between histology and glycolytic
      status.
AB  - The success of tumor imaging with PET and 2-deoxy-2-fluoro[18F]-D-glucose (18FDG)
      is based on preferential accumulation of 18FDG in tumors. METHODS: Fluorine-18
      FDG uptake was measured in nine human cancers heterotransplanted in nude mice and
      compared with histologic subclassification. RESULTS: Mean 18FDG uptake by the
      human cancers was considerably less than that by the host's heart, but values at
      60 min after injection were about 2.5 times as high as the liver and kidney,
      about two times as that for the muscle and about six times that for the blood.
      Comparison of 18FDG uptake and histological grade in four gastric, two pancreatic
      and three colonic cancers showed that 18FDG uptake increased with loss of
      differentiation. CONCLUSION: This nude mice model system is useful for studying
      correlations between physiological and morphological parameters of
      heterotransplanted human cancers.

PMID- 8271071
TI  - Personal risk assessment under the Americans with Disabilities Act. A decision
      analysis approach.
AB  - A decision analysis model was designed and implemented to facilitate job
      placement decisions. It identified relevant input parameters such as typical
      probability and severity of adverse outcomes for three targets--the worker
      himself or herself, the public, and productivity. In addition, specific factors
      that differentiate this specific decision instance from the "typical" are
      identified, including a person's specific health history, job site risk
      modifiers, and possible accommodation methods. Relevant societal values are also
      integrated, including relative importance of the three target groups (person,
      public, productivity) and discounting of the importance of future events. The
      system also includes a calculation engine to quantitatively integrate these input
      parameters for any number of events and modifiers to yield a single cost
      (expected negative utility value) for the instant situation. Cost represents risk
      of substantial harm, not financial cost. The decision analysis model is
      illustrated using a progressively more complex series of decision examples. In
      addition, the method of sensitivity analysis is applied, determining the extent
      to which the outcome is affected by varying the value assigned to an uncertain
      input parameter. This decision analysis approach is useful both as a heuristic
      (explaining the process) and as an aid in decision-making for a person with
      disabilities. The recently implemented Americans with Disabilities Act requires
      that a rational approach be utilized in such decisions, and such a model may
      facilitate this process.

PMID- 8271072
TI  - Evolution of an on-site industrial physical therapy program.
AB  - This article describes the growth and cost benefits of an on-site industrial
      physical therapy program. The program was initiated in 1982 at one of five plants
      managed by a major corporation to help reduce the costs of musculoskeletal
      injury. A significant reduction in the occupational absence rate was noted at the
      plant with the physical therapy program. Now in its tenth year, the program has
      produced calculated savings of $8.3 million, a benefit-to-cost ratio of greater
      than 9 to 1. The physical therapy program now serves approximately 50% of the
      company's employees and provides technical assistance in solving other work
      related problems.

PMID- 8271073
TI  - Assessment of the accuracy of physical activity questionnaire occupational data.
AB  - The validity and reliability of occupational physical activity data from survey
      instruments were determined in 75 men and women (age 23 to 59 years) in white
      collar jobs. Data were validated against measures of cardiorespiratory fitness,
      body fatness, motion detection, pulmonary function, and 12 days of occupational
      physical activity records. More than 90% of occupational physical activity was
      spent in light-intensity sitting, standing, and walking. Test-retest reliability
      was high for most occupational questions (r > or = .63, P < .05). Correlation
      coefficients between questionnaire data and validation criteria that reflect
      heavy-intensity physical activity were low (r < .17, P > .05). The modified
      Tecumseh Occupational Questionnaire and Seven-Day Recall, which classified
      occupational physical activity in hours per week worked and average level of
      ratio of associated metabolic rate for a specific activity divided by the resting
      metabolic rate, on the job, correlated best with physical activity records (r =
      .11 to .47). Validation of these self-administered questionnaires in populations
      with a greater diversity of jobs and occupational energy requirements is needed.

PMID- 8271074
TI  - Lung function in workers refining phosphorus rock to obtain elementary
      phosphorus.
AB  - Elevated levels of phosphoric acid, phosphorus pentoxide, fluorides and coal tar
      pitch volatiles were present in workplace air of a two-oven industrial refinery.
      One hundred thirty-one workers prospectively underwent annual pulmonary function
      testing (forced vital capacity, forced expiratory volume in 1 second, and forced
      expiratory flow). Regression of these spirometric data, analyzed longitudinally
      over 3 to 7 years and also cross-sectionally reveals no residual significant
      effect of industrial exposure after adjusting for the effect of age and smoking.
      This industrial exposure contributes only weakly and inconsistently to the well
      documented reduction of spirometric lung function that occurs from smoking alone.
      No significant reductions of spirometry occurred in exposed nonsmokers or former
      smokers.

PMID- 8271075
TI  - Validation of occupational hand use categories.
AB  - As part of a study of the etiology of carpal tunnel syndrome in industry, we
      developed a measure of occupational hand use activities, "Occupational Hand Use"
      (OHU), using 471 workers from four industries. This categorization has five
      categories based primarily upon observed relative force and secondarily upon
      observed relative repetitions. Because the validity of this OHU categorization
      has been questioned, we devised a study to validate this variable by
      demonstrating its reliability. Using discriminant analysis, we show that the OHU
      categorization accurately reflects the subjective impressions of other industrial
      workers (605 workers from four other industries in the United States and Japan).
      Within each validation industry, 68 to 88% of all workers were classified
      precisely to the correct OHU category, and an additional 10 to 25% were
      classified to within one OHU category, for a hit or near-miss rate of 87 to 98%.
      The major classification error was due to some workers overestimating the
      repetitiousness of their jobs. An equation for calculating OHU from subjective or
      objective data is provided.

PMID- 8271076
TI  - Disposable protective eyewear devices for health care providers. How important
      are they and will available designs be used?
AB  - The objective of this study was to assess the efficacy of five types of
      disposable protective eyewear devices, to determine variables affecting
      compliance with the use of protective eyewear, and to determine the frequency of
      subclinical eye splatter. One hundred volunteer health care providers were
      assigned to one of five study eyewear groups and given a protective eyewear
      device to use for 2 weeks in an urban teaching referral center. Questionnaires
      were used to survey eyewear habits and other variables before the study. The
      devices were determined to be 88% effective overall, and there was no
      statistically significant difference between groups. The incidence of subclinical
      splatter was 50%. Even though disposable eyewear devices providing full frontal
      and lateral eye coverage are effective in preventing eyesplatter, the incidence
      of eyesplatter among health care providers working in nonsurgical areas is more
      common than previously assumed because of the lack of recognition of splatter
      (subclinical splatter) by the workers.

PMID- 8271077
TI  - Blood exposure and the risk of hepatitis B virus infection in firefighters.
AB  - The risk of infection with bloodborne pathogens among public safety workers is
      not well defined. This survey assessed personal and occupational risk factors
      among uniformed fire department employees by a self-administered questionnaire
      and hepatitis B virus (HBV) infection status by serologic testing. Overall, 46
      (7.8%) of 592 employees had past or current hepatitis B virus infection.
      Employees reporting blood contact with skin had been infected more often than
      employees without this exposure (11% vs 5.8%, prevalence ratio = 1.9, 95%
      confidence interval, 1.1, 3.3). Prevalence of infection did not differ by age,
      years on the job, or job duties. The adjusted prevalence of hepatitis B virus
      infection among male employees (4.5%) was not significantly different than the
      prevalence in American men (6.8%) (P = .17). Although the overall risk of
      hepatitis B virus infection is not greater among fire department employees than
      the general population, blood contact with skin may elevate this risk.

PMID- 8271078
TI  - Investigation of hematuria at a printing company.
AB  - An investigation was undertaken at a printing company into an apparently high
      prevalence of trace dipstick hematuria discovered during routine medical
      examinations. In both the printing employees (n = 225) and a control group (n =
      118) from other industries, the prevalence of hematuria exceeded that described
      in most previous reports (31% and 25%, respectively, using the criterion of > 12
      glomerular red cells or > 2 nonglomerular red cells/microliter of urine). No
      focus of abnormality was identified within the printing plant and no association
      was identified between reported exposure to potentially toxic substances and the
      degree of hematuria. An occupational hygiene inspection and medical follow-up of
      selected workers did not reveal any significant abnormalities. The limitations of
      available information concerning "normal" urinalysis results suggests that
      hematuria may not be a useful test for the screening of occupational groups at
      risk of bladder cancer.

PMID- 8271079
TI  - An international marketing representative of our company plans a trip to east
      Africa within the next 2 months. This will also entail some travel away from
      metropolitan areas. What is your advice concerning malaria prophylaxis?

PMID- 8271080
TI  - The effectiveness of preemployment drug screening in the prediction of employment
      outcome.

PMID- 8271081
TI  - Drug use: association vs causation.

PMID- 8271082
TI  - Relation between exercise and absenteeism due to illness and injury in
      manufacturing companies in Japan.
AB  - The relation between exercise and absenteeism due to illness and injury was
      assessed in 21,924 male workers. Exercisers I (engaging in exercise less than
      once a week), II (once or twice a week), and III (more than three times a week)
      had a significantly lower incidence of absence than nonexercisers. The proportion
      of cases of absence in exercisers I, II, and III was 10%, 10%, and 14% lower,
      respectively, than that of nonexercisers. The number of days absent among
      exercisers I, II, and III was 48%, 43%, and 26% lower, respectively, than among
      nonexercisers. Controlling for confounding factors by logistic analysis,
      significantly reduced relative risk of absence persisted among exercisers I, II,
      and III versus nonexercisers at 0.88, 0.90, and 0.87, respectively. These
      findings indicate that worker exercise was associated with absence due to illness
      and injury.

PMID- 8271083
TI  - Diagnostic strategies in the management of acute upper gastrointestinal bleeding:
      patient and physician preferences.
AB  - BACKGROUND: Routine diagnostic endoscopy is commonly obtained for low-risk
      patients with acute upper gastrointestinal bleeding despite evidence from
      controlled trials that it does not improve patient outcome. OBJECTIVE: To
      determine whether endoscopy is being overutilized for these patients or whether
      considerations not addressed in the trials could justify its widespread use.
      METHODS: Twenty-five patients recovering from a recent hemorrhage and 22 primary
      care physicians used the analytic hierarchy process to perform an individualized
      analysis regarding the diagnostic management of acute upper gastrointestinal
      bleeding. The results were used to determine whether routine endoscopy was
      consistent with each subject's interpretation of relevant data and judgments
      regarding the relative importance of five management goals. The authors then
      compared the proportion of subjects in each group who preferred endoscopy over
      two non-endoscopy strategies (upper gastrointestinal series and no routine
      diagnostic test) with 85%, the current rate of endoscopy at the authors'
      hospital. RESULTS: Endoscopy was preferred by 92% (97.5% CI: 70%-98%) of the
      patients and 55% (97.5% CI: 31%-77%) of the physicians. The patients ranked
      identifying the cause of bleeding the second most important management goal after
      avoiding a poor outcome from the acute bleeding episode. CONCLUSIONS: The current
      rate of diagnostic endoscopy is higher than would be expected based on
      physicians' preferences but quite consistent with patients' preferences. Patients
      regard knowledge of the bleeding site as important, even if this information will
      not affect management or prognosis. Attempts to assess the use of diagnostic
      endoscopy and other diagnostic tests should take both patient preferences and the
      pure value of diagnostic information into account.

PMID- 8271084
TI  - Psychiatric disorders and functional impairment in patients with persistent
      dizziness.
AB  - OBJECTIVE: To determine the prevalence and predictors of psychiatric dizziness
      and to measure functional impairment associated with dizziness. DESIGN:
      Consecutive outpatients with a chief complaint of dizziness. SETTING: Four
      outpatient clinics at a military teaching hospital. PATIENTS: 100 dizzy patients
      and 25 control patients. MEASUREMENTS AND MAIN RESULTS: Structured psychiatric
      interviews were conducted using the Diagnostic Interview Schedule, and functional
      status was assessed with the Sickness Impact Profile and the 20-item MOS (Medical
      Outcomes Study) Short-Form. Psychiatric disorders were a primary or contributory
      cause of dizziness for 40% of the dizzy patients. Compared with the control
      patients, the dizzy patients had a higher lifetime (46% vs 32%) as well as recent
      (37% vs 20%) prevalence of axis I disorders. The greatest differences were in
      disorders of depression and somatization. The dizzy patients had a higher
      lifetime prevalence (23% vs 8%) as well as recent history (11% vs 0%) of major
      depression or dysthymia. Also, somatization disorders were strikingly more common
      among the dizzy patients than among the control patients (37% vs 8%, p = 0.005),
      with the dizzy patients reporting more than three times as many psychiatric or
      unexplained physical symptoms (5.2 vs 1.5). Age < 40 years, related complaints of
      weakness or headaches, and dizziness provoked by hyperventilation or standing
      were independent predictors of psychiatric dizziness. The dizzy patients reported
      moderate functional impairment, which was most severe among those with
      psychiatric disorders. CONCLUSIONS: Persistent dizziness is associated with
      increased functional impairment and psychiatric comorbidity, particularly
      depression and somatization. Moreover, psychiatric disorders aggravate the
      impairment that occurs with dizziness alone.

PMID- 8271085
TI  - Intravenous heparin dosing: patterns and variations in internists' practices.
AB  - OBJECTIVE: To characterize internists' dosing practices when administering and
      adjusting intravenous heparin regimens. DESIGN: A survey administered by
      physician-investigators. SETTING: Two community teaching hospitals and one
      Veterans Affairs Medical Center. SUBJECTS: Sixty-one attending physicians in
      internal medicine. MEASUREMENTS: Physicians' choices of therapeutic activated
      partial thromboplastin time (APTT) range, initial heparin bolus, initial infusion
      dose, and dose/infusion adjustments when APTT levels are < 1.2 x control (< 35
      seconds), 1.2-1.5 x control (35-45 seconds), 1.5-2.3 x control (46-70 seconds),
      2.3-3.0 x control (71-90 seconds), and > 3.0 x control (> 90 seconds). RESULTS:
      Physicians' dosing decisions and therapeutic ranges during heparin treatment
      varied widely. Responses to nontherapeutic APTT levels had especially high
      coefficients of variation (0.67-0.81). Two groups of physicians, together
      comprising a majority of all respondents, use mutually exclusive therapeutic
      ranges (mean 44-56 seconds and 60-83 seconds). These two groups differ
      significantly in several types of dosing decisions. CONCLUSION: In the absence of
      generalizable standard guidelines for intravenous heparin therapy, internists'
      dosing practices vary widely. Because such practices may impede timely, effective
      anticoagulation, experimental studies comparing standardized dosing protocols are
      needed.

PMID- 8271086
TI  - The framing effect of relative and absolute risk.
AB  - OBJECTIVE: To test whether a patient's perception of benefit is influenced by
      whether the benefit is presented in relative or absolute terms. DESIGN:
      Questionnaire-based study. SETTING: A general medicine outpatient clinic at a
      rural tertiary care center associated with a medical school. PATIENTS: 470 of 511
      consecutive patients who agreed to answer a questionnaire while waiting for their
      clinic visit. Mean age was 49.1 years, 62.1% were female, and 51.9% had at least
      one year of education beyond high school. MAIN OUTCOME MEASURES: Patient response
      to the choice of two equally efficacious medications for the management of a
      hypothetical serious disease. The benefit of one medication was stated in
      relative terms, the other in absolute terms. Patients could choose either
      medication alone, indicate indifference to the choice of medication, or choose
      not to answer. MAIN RESULTS: 56.8% of the patients chose the medication whose
      benefit was in relative terms. 14.7% chose the medication whose benefit was in
      absolute terms. Only 15.5% were indifferent to the choice of medication. The
      patients preferred the medication whose benefit was in relative terms across a
      wide range of ages and educational levels. Further questioning suggested that the
      patients thought benefit was greater when expressed in relative terms because
      they ignored the underlying risk of disease and assumed it was one. CONCLUSIONS:
      The "framing" of benefit (or risk) in relative versus absolute terms may have a
      major influence on patient preference.

PMID- 8271087
TI  - Physician advice to quit smoking: results from the 1990 California Tobacco
      Survey.
AB  - OBJECTIVE: To estimate the percentage of California smokers who visit physicians
      each year and thus determine the extent of the opportunity for physicians to
      advise their smoking patients to quit; to identify sociodemographic and other
      characteristics related to smokers' reporting that advice was given; and to look
      for evidence that physician advice influences quitting behavior. SETTING AND
      DESIGN: Data were collected as part of the 1990 California Tobacco Survey, a
      large (n = 24,296) population-based telephone survey. PARTICIPANTS: 9,796 current
      smokers, including 5,559 daily smokers who had visited a physician in the
      preceding year. MEASUREMENTS AND MAIN RESULTS: Two-thirds of all smokers had
      visited a physician in the year before the interview, but only about 50% of
      Hispanic and Asian smokers had done so. Multivariate analysis showed that advice
      at the last visit was independently related to older age, higher cigarette
      consumption, and poorer perceived health. Compared with smokers never advised to
      quite by a physician, those advised to quit at the last visit were 1.61 (95%
      confidence interval, 1.31-1.98) times more likely to report a quit attempt in the
      preceding year and 1.90 (95% confidence interval, 1.45-2.48) times more likely to
      be preparing to quit; however, those advised previously but not at the last visit
      showed no more quitting activity than did smokers never advised to quit.
      CONCLUSION: Physicians have considerable opportunity to reach all demographic
      subgroups of the population, but the nature of the subgroups advised most (those
      who are older, have high consumption of cigarettes, or have poor health) suggests
      that physicians tend to treat such advice as a therapeutic rather than a
      preventive intervention. Physician advice at the most recent visit encourages
      patients to think about quitting and probably leads to quit attempts. Thus, it is
      vital that physicians perform the simple intervention of advising every smoker to
      quit at every visit.

PMID- 8271088
TI  - Practice patterns and the adequacy of residency training in consultation
      medicine.
AB  - OBJECTIVE: To describe consultation practice patterns of graduates of an internal
      medicine residency program and to determine whether they consider themselves to
      be adequately trained to practice in the area of internal medicine consultations.
      DESIGN: The authors surveyed graduates of the internal medicine residency program
      at the University of California, San Diego, School of Medicine from 1980 to 1989.
      Respondents described their practice types and the mechanics of consultations
      they currently perform, as well as the adequacy of their training in and
      frequency of encountering 74 clinical problems in the area of internal medicine
      consultation. Topics were categorized as Group I: excessive training; Group II:
      adequate training, frequently encountered; Group III: adequate training,
      infrequently encountered; Group IV: inadequate training, frequently encountered;
      and Group V: inadequate training, infrequently encountered. SETTING: University
      teaching hospital. PARTICIPANTS: Of 214 graduates, 91 returned surveys adequate
      for analysis. RESULTS: Internists prefer verbal communication with their
      colleagues and seeing surgical patients in the office prior to admission.
      Residents perceive that they have been excessively trained in preoperative
      evaluations of the asymptomatic and chronically ill adult and in several
      postoperative complications. Topics seen frequently in clinical practice but
      inadequately taught include: issues in convalescence and rehabilitation from
      surgical procedures, use of psychotropic medications, and management of eating
      disorders. CONCLUSIONS: To prepare residents for practice, program directors in
      consultation medicine might consider incorporating outpatient preoperative
      evaluation assessments, encouraging a liaison between surgeons and internists,
      and modeling verbal communication among colleagues. Consideration should be given
      for more didactic training for Group IV topics.

PMID- 8271089
TI  - The uses of shadowing the doctor--and patient: on seeing and hearing their work
      of care.

PMID- 8271090
TI  - Chronic obstructive pulmonary disease: less common causes--an algorithm for the
      primary care physician.
AB  - The clinical features and distinguishing characteristics of the less common
      causes of chronic airflow obstruction have been reviewed. Clearly, the majority
      of patients have cigarette-induced chronic bronchitis and/or emphysema. However,
      for those patients with chronic airflow obstruction who are younger than 40 years
      old and/or have no or modest (less than 20 pack-years) smoking histories, a
      detailed assessment is warranted. A logical approach to the evaluation of the
      patient with dyspnea and chronic airflow obstruction has been outlined, with the
      goal of identifying those patients with potentially reversible disease, and to
      underscore the fact that not all "COPD" is due to cigarette smoking.

PMID- 8271091
TI  - Is cardiac test availability a significant factor in weekend delays in discharge
      for chest pain patients?
AB  - The authors assessed whether the lack of weekend cardiac test availability
      significantly contributed to weekend delays in hospital discharge for "low-risk"
      chest pain patients. Mean lengths of stay were compared for late-week versus
      early-week admissions. Patients with late-week admissions had a 19% greater
      length of stay than did patients admitted earlier in the week (2.36 +/- 1.87 vs
      1.91 +/- 1.21 days, p = 0.10, with p = 0.015 after adjusting for severity of
      illness). Cardiac diagnostic tests were ordered for only 4% of study patients.
      Therefore, the "weekend effect" existed in an environment where cardiac
      diagnostic tests were infrequently ordered.

PMID- 8271092
TI  - Faculty perceptions of effective ambulatory care teaching.
AB  - The authors interviewed faculty members to determine their perceptions of what
      constitutes effective teaching in the ambulatory setting. They conducted
      semistructured interviews with experienced clinician-tutors who supervise
      residents in two internal medicine clinics. Tutors identified similarities as
      well as important differences between inpatient teaching and outpatient teaching.
      Questioning, role modeling, and emphasizing general principles and concept
      comprehension can be used effectively in both settings. On the other hand, the
      two settings differ strikingly in teaching of problem solving, bedside teaching,
      and provision of feedback. Many characteristics of the setting influence
      outpatient teaching, but the tutors offered differing viewpoints about whether
      these characteristics are beneficial or detrimental.

PMID- 8271093
TI  - Practice satisfaction and dissatisfaction in general internal medicine
      departments of large multispecialty clinics.
AB  - General internal medicine (GIM) physician practice satisfaction and
      dissatisfaction in large multispecialty clinics were assessed utilizing a survey
      designed to elicit physician perceptions of practice. 420 GIM physicians in 22
      multispecialty clinics were contacted, and 168 participated in the survey. The
      most significant positive components of practice satisfaction were patient
      interactions and favorable physician colleague interactions. The prominent
      negative components were paperwork hassles and perceived "second-class" physician
      status. Coping strategies were varied and included increased political
      involvement, career change, and withdrawal via depression.

PMID- 8271094
TI  - When doctor and patient disagree.

PMID- 8271095
TI  - Dizziness and psychiatric disease.

PMID- 8271097
TI  - Fluoride program project: year one.
AB  - The public health use of fluoride in community water supplies for the prevention
      of dental caries is accepted worldwide, and the safety and efficacy of its use in
      trace concentrations in this manner have been repeatedly documented. Because of
      its cariostatic property, fluoride is increasingly being added to other dental
      health products, and the resulting increase in exposure of populations to
      fluoride has renewed consideration of the margin of safety which exists between
      safe and toxic levels of fluoride exposure. There is cause for concern,
      particularly in cases where fluoride metabolism may be altered by impaired
      physiological function. Because of this, investigators at the Oral Health
      Research Institute of the Indiana University School of Dentistry are currently
      conducting a series of studies as part of a five-year NIDR-funded Program Project
      to study the pharmacological effects of fluoride in selected human and animal
      populations. This article briefly summarizes results from the first year of the
      five-year program.

PMID- 8271096
TI  - Current thoughts on prudent fluoride use.
AB  - In spite of advances made during the past two decades, dental caries continues to
      be the major oral disease. The most effective means for the prevention and
      control of dental caries continues to be the professional, public health, and
      home use of fluoride. However, prudent use of these measures is required to
      minimize the risks of dental fluorosis in young children.

PMID- 8271098
TI  - Fluoride: safety issues.
AB  - Fluoride has been used widely in dentistry to prevent dental caries. While there
      is little doubt regarding its efficacy, the safety of fluoride has been a
      controversial issue. Abundant scientific data accumulated over the years have
      demonstrated that other than dental fluorosis, there are no known adverse effects
      of long-term fluoride ingestion for caries prevention. However, the risk of an
      overdose is real, and it can result in serious acute toxicity, even death.
      Understanding potential risks and taking cautions can virtually eliminate the
      acute adverse effects of fluoride. These potential risks need to be recognized in
      order to take full advantage of fluoride's benefits.

PMID- 8271099
TI  - Fluoride: the difference between prevention and restoration.

PMID- 8271100
TI  - The efficacy of administering blood transfusions at home to terminally ill cancer
      patients.
AB  - Comfort care for cancer patients in the terminal stage has been the goal of
      hospice programs since their inception. Among the many treatment modalities
      available to homebound patients, transfusions have been little studied for their
      effects on advanced disease symptoms, particularly for those in the terminal
      phase. Our work in a hospital-based home care program established in 1978 led us
      to believe that blood transfusions neither slowed the progress of symptoms nor
      relieved their severity. Our hypothesis being that transfusions do not improve or
      significantly change the quality of life of terminally ill patients, we studied
      24 men and women with various forms of advanced cancer. The only significant
      clinical difference between pre- and post-transfusion variables was in
      hematocrit. In the subjective testing, the only significant difference was in the
      quality of life index completed by the patient. This result could be interpreted
      as a positive psychological benefit from blood transfusions. The results of other
      subjective tests, although statistically less significant, also showed a trend
      toward psychological benefit from transfusions. It would be necessary to carry
      out studies with a larger sample to conclude that this is indeed the case.

PMID- 8271101
TI  - Difficulties in developing a respite program.
AB  - St. Paul's Hospital Palliative Care Unit is a 15-bed integrated AIDS and non-AIDS
      unit that has been open since 1989. A respite program has also been operating
      since 1989. Overall admissions to the unit have comprised approximately one-third
      AIDS patients and two-thirds non-AIDS patients. However, the respite patients
      have consisted of about two-thirds AIDS patients and one-third non-AIDS patients.
      The 53 patients in the first three years of the respite program have generated 96
      respite admissions and 37 non-respite admissions. In the course of developing
      this program a number of questions and issues have arisen relating to goals and
      objectives of the respite program, perceptions of the patient and caregivers, and
      the effectiveness of the program. A review of the utilization patterns of this
      program and a discussion of selected case histories will be instructional for
      those who are considering developing their own respite programs.

PMID- 8271102
TI  - In the darkness of the shadow of death: a ray of hope: the story of Hospice
      Africa.

PMID- 8271103
TI  - Consciously walking the fine line: thoughts on a hospice response to assisted
      suicide and euthanasia.

PMID- 8271104
TI  - A statement of assumptions and principles concerning psychological care of dying
      persons and their families. Psychological Work Group of the International Work
      Group on Death, Dying, and Bereavement.

PMID- 8271105
TI  - Can there be hope without justice?

PMID- 8271106
TI  - Palliative care in central Sydney: the Royal Prince Alfred Hospital as catalyst
      and integrator.

PMID- 8271107
TI  - Medical care in hospice day care.

PMID- 8271108
TI  - A clinical note on sublingual buprenorphine.

PMID- 8271109
TI  - On the "last days of life".

PMID- 8271110
TI  - Medical investigation in the elderly: the geriatrician's dilemma.

PMID- 8271111
TI  - Photomodulation of glutamate dehydrogenase properties by red light.
AB  - To gain some insight into the mechanism by which red light-biosystem interaction
      occurs, an investigation was made of certain features of purified glutamate
      dehydrogenase from beef liver (E.C. 1.4.1.3.) irradiated with either an He-Ne
      laser (632.8 nm) or a red light-emitting diode (650 +/- 20 nm). In both cases the
      energy dose was 0.24 J cm-2. Significant changes in the glutamate dehydrogenase
      extinction coefficient measured at 275 nm, the capability of the enzyme to bind
      the reduced form of nicotinamide adenine dinucleotide (NADH), certain kinetic
      parameters, the pH and temperature dependence and the sensitivity to guanosine 5
      triphosphate (GTP) and adenosine diphosphate (ADP) were found, probably due to
      the interaction of light with a protein domain containing a metal ion or ions. He
      Ne laser and diode irradiation were found to differ with regard to their
      interaction with glutamate dehydrogenase. Interestingly, different effects were
      also found when an He-Ne laser and a non-coherent Xe-Hg lamp were used to
      irradiate glutamate dehydrogenase under the same experimental conditions. This
      confirms that non-coherent light at various power levels affects the isolated
      glutamate dehydrogenase.

PMID- 8271112
TI  - Electron transfer from triplet thymine and thymidine to lipoic acid.
AB  - Electron transfer from the triplet excited state of thymine or thymidine to the
      disulphide compound lipoic acid (RSSR) was studied using KrF laser flash
      photolysis (248 nm, 20 ns). The electron transfer reaction rate constants,
      measured at 310 nm, were determined to be 1.3 x 10(10) M-1 s-1 and 6.9 x 10(9) M
      1 s-1 for thymine and thymidine respectively. The transient absorbance at 400 nm
      in the presence of the quencher is attributed to the anion radical of lipoic
      acid.

PMID- 8271113
TI  - Spectroscopic studies of tin ethyl etiopurpurin in homogeneous and heterogeneous
      systems.
AB  - Tin ethyl etiopurpurin is a promising second generation photosensitizer for
      photodynamic treatment of cancer. This compound is only poorly soluble in aqueous
      media and, therefore, needs a delivery system for administration to animals.
      Successful tumor eradication has previously been reported, following light
      exposure of rats previously administered with the purpurin formulated as a
      Cremophor El emulsion, in dipalmitoyl-phosphatidyl-choline liposomes or with
      gamma cyclodextrins. In this paper, we describe some absorbance and fluorescence
      studies of tin ethyl etiopurpurin in homogeneous and heterogeneous systems. In
      general, absorption and emission maxima were found to be red shifted as the
      environment changed from polar to non-polar. The viscosity and dielectric
      constant of the medium affected the purpurin fluorescence intensity. The liposome
      preparations were characterized by particle size determination, differential
      scanning calorimetry and by sensitizer fluorescence quenching studies.
      Photobleaching studies also showed variation owing to changes in the environment
      in which the dye was located.

PMID- 8271114
TI  - Lowest excited triplet states of hypericin and isohypericin.
AB  - The fluorescence and phosphorescence of hypericin and isohypericin were studied
      in an ethanol matrix at 1.2 K. The prompt fluorescence spectra are mirror images
      of the absorption around the 0-0 transition, as expected. The 0-0 vibronic lines
      of the phosphorescence are found at 13,190 and 13,622 cm-1, and the
      phosphorescence decay times are 2.79 and 6.6 ms at 1.2 K for hypericin and
      isohypericin respectively. The fluorescence excitation spectrum of isohypericin
      reveals a small trace of a different pigment, possibly a tautomeric form of
      isohypericin. The decay of the phosphorescence of isohypericin is biexponential.
      The slow component is attributed to an unknown contaminant with a high quantum
      yield of phosphorescence.

PMID- 8271115
TI  - Analysis of mutations induced by 4'-hydroxymethyl-4,5',8-trimethylpsoralen and
      UVA in Escherichia coli lac Z gene and its regulatory region.
AB  - The mutagenic consequences of covalent adducts induced in M13mp19 DNA by 4'
      hydroxymethyl-4,5',8-trimethylpsoralen (HMT) and UVA have been determined in a
      forward mutational system capable of detecting all classes of mutagenic events.
      The photoreaction mediated by HMT has been carried out at a very low molar ratio
      of HMT to DNA which favours the induction of cross-links between high affinity
      reaction sites. When damaged M13mp19 DNA is used to transfect competent
      Escherichia coli K12 JM105 cells, a five-fold increase in mutation frequency is
      observed at 3.5% survivors when measured as a loss of beta-galactosidase alpha
      complementation. The enhanced mutation frequency is largely due to base
      substitutions, frameshift events and large deletions. The single nucleotide
      substitutions occur both in the lac Z coding sequence and in its regulatory
      region. Transversion and transition have been detected with a predominant form
      consisting of A.T-to-G.C transversion at position +159. Frameshift mutations have
      been observed at five positions while three large deletions removing either part
      of the coding sequence or both the coding and the regulatory regions have been
      detected with a higher frequency. The spectrum of base substitutions detected
      between the M13 lac Z- phages surviving to the treatment is totally different
      from those appearing spontaneously whereas several frameshift events or deletions
      can already be detected between the spontaneous mutations. Despite the presence
      of these spontaneous hot spots, the spectrum of mutations recovered after HMT
      photoaddition appears to be unique and a detailed analysis of the different
      classes of mutations indicates an important role of cross-links in the production
      of mutations.

PMID- 8271116
TI  - Phototransformation of monovinyl and divinyl protochlorophyllide by
      NADPH:protochlorophyllide oxidoreductase of barley expressed in Escherichia coli.
AB  - The chlorophyll precursors monovinyl protochlorophyllide (MV-PChlide) and divinyl
      protochlorophyllide (DV-PChlide) were extracted from mutant C-2A' of the
      unicellular green alga Scenedesmus obliquus which accumulates both
      protochlorophyllide derivatives in the dark. The two pigments were characterized
      by absorption and fluorescence spectroscopy and by plasma desorption mass
      spectrometry. The molecular masses of MV-PChlide and DV-PChlide were determined
      as 612 and 610 atomic mass units (amu) respectively. Both MV-PChlide and DV
      PChlide were accepted as substrates and photoconverted to chlorophyllides in
      vitro by NADPH:protochlorophyllide oxidoreductase of barley expressed in
      Escherichia coli.

PMID- 8271117
TI  - Flavone photoreactivity. UV-induced reactions in organic solvents and micellar
      systems.
AB  - Flavonoid photochemistry is a subject of interest in studies dealing with the
      role of phenolic compounds as screening pigments in plants. In order to
      contribute to the understanding of the processes involved in the interaction
      between flavonoids and UV radiation, we have studied UV-induced flavone
      photodegradation in both organic solvents and micellar systems. The results
      obtained show that flavone photosensitivity depends on the characteristics of the
      reaction environment and is influenced by the medium polarity and the charges on
      the micellar surface. Qualitative and quantitative differences in the
      photodegradation products were demonstrated by high performance liquid
      chromatography (HPLC) analysis.

PMID- 8271118
TI  - Photosensitized cleavage and cross-linking of pBR322 DNA with khellin and
      visnagin.
AB  - The naturally occurring furanochromones khellin and visnagin have received
      considerable attention, largely because of their vasodilatory properties and of
      their ability (particularly that of khellin) to induce skin pigmentation upon
      ultraviolet light treatment of patients suffering from vitiligo. There are
      conflicting statements in the literature on whether or not they are capable of
      cross-linking DNA photochemically. Supercoiled and linear pBR322 DNA was used to
      probe this reaction. The results showed that both khellin and, to a greater
      extent, visnagin photosensitized DNA cross-linking. In addition, both
      photosensitizers induced extensive DNA cleavage.

PMID- 8271120
TI  - Dyspepsia in children.

PMID- 8271119
TI  - Interactions of dicarboxylic porphyrins with membranes in relation to their
      ionization state.
AB  - The interactions of dicarboxylic porphyrins with membrane systems are discussed
      with particular emphasis on the effect of the charge of the porphyrin and the
      nature of the side-chains. The incorporation of hematoporphyrin or related
      dicarboxylic porphyrins within small unilamellar vesicles as membrane models is
      favored by a decrease of the pH in the range of physiological pH values. This
      effect might play an important role in the retention of porphyrins by tumors,
      which are more acidic than normal tissues. Kinetics studies also show that the
      partition of the porphyrin between the lipidic bilayer and the aqueous phase is
      governed by its release rate rather than by its incorporation rate.

PMID- 8271121
TI  - The constitutive exocytotic pathway in microvillous atrophy.
AB  - Microvillous atrophy is a disorder within the intractable diarrhea of infancy
      syndrome. The disease is believed to stem from a transport defect that prevents
      exocytosis of brush border-related material. We investigated this hypothesis by
      examining the direct constitutive exocytotic pathway using sucrase-isomaltase as
      a representative protein. We also studied various other brush border and
      lysosomal marker enzymes. The biosynthesis and localization of selected
      intestinal epithelial enzymes were studied in small-intestinal mucosal biopsy
      specimens from a total of nine children with microvillous atrophy by: (a)
      metabolic labeling in organ culture, (b) radioiodination and immunoprecipitation,
      (c) indirect immunoperoxidase immunocytochemistry, and (d) immunogold electron
      microscopy. The results demonstrated that brush border enzymes were synthesized
      normally and could be located in the apical brush border membrane and on
      microvillous membrane within microvillous inclusions. Brush border enzymes were
      not detected in the "secretory granules" that accumulated within the apical
      cytoplasm of epithelial cells. Lysosomal enzymes were only detected within
      lysosomal bodies. Thus, the direct constitutive pathway is not involved in
      microvillous atrophy, and a disturbance of endocytosis or the indirect
      constitutive pathway is unlikely. Any transport defect in the disease probably
      involves a different, unidentified exocytotic pathway.

PMID- 8271122
TI  - Interleukin-2 production in pediatric inflammatory bowel disease: evidence for
      dissimilar mononuclear cell function in Crohn's disease and ulcerative colitis.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) represent clinically distinct
      chronic inflammatory bowel diseases (IBD) of unknown etiology. Although the
      mucosal immune system is implicated in their pathogenesis, immunological
      differences between the two disorders are not well defined. The aim of this study
      was to compare in vitro mucosal T-lymphocyte function in CD and UC. Peripheral
      blood mononuclear cell interleukin-2 (IL-2) production was similar in pediatric
      IBD and control patients under unstimulated conditions, but was significantly
      increased in response to phytohemagglutinin (PHA) stimulation for the UC group.
      Lamina propria mononuclear cells (LPMNC) isolated from colonic resections in IBD
      patients had significantly lower spontaneous proliferation and IL-2 production in
      vitro than did LPMNC of control patients. In contrast, significantly greater IL-2
      production was detected when the LPMNC of CD patients were cultured with PHA, in
      comparison with those of UC or control patients. When indomethacin, a
      prostaglandin synthetase inhibitor, was added to the cultures, significantly
      increased IL-2 secretion was observed for CD LPMNC, but not for UC cultures,
      under both stimulated and unstimulated conditions. These findings demonstrate
      abnormal LPMNC IL-2 production in IBD. Furthermore, our data suggest that
      inhibition of the prostaglandin synthetase pathway upregulates IL-2 production by
      LPMNC in CD. These results support the hypothesis that immunoregulatory
      mechanisms controlling IL-2 production differ between CD and UC.

PMID- 8271123
TI  - Ultrastructural changes in the duodenal mucosa of HIV-infected children.
AB  - We studied the ultrastructure of duodenal biopsy specimens from six HIV-infected
      children with chronic gastrointestinal symptoms. A monomorphic pattern of
      microvillar damage (short and irregular microvilli, joined at their bases) was
      seen in all cases, even when the mucosa was normal on conventional histology.
      Among nine HIV antibody negative children, a similar pattern was seen only in
      three out of four celiac children with severely atrophic mucosa. No viral,
      bacterial, or protozoan pathogen was found. In HIV-infected children
      tubuloreticular inclusions were also seen in endothelial cells. These
      ultrastructural changes could help to account for the gastrointestinal symptoms
      in HIV-infected children.

PMID- 8271124
TI  - The diagnostic value of the gliadin antibody test in celiac disease in children:
      a prospective study.
AB  - Serum gliadin antibodies (IgA/IgG) were determined in 191 consecutive children
      (median age, 2.75 years; range, 0.33-15.5 years) admitted for a small-intestinal
      biopsy on suspicion of celiac disease. The test was a diffusion-in-gel enzyme
      linked immunosorbent assay (DIG-ELISA). Of these 191, 14 (7.3%) appeared to have
      untreated celiac disease. Depending on the choice of cut-off value of the test
      (combined determination of IgA and IgG), the sensitivity was 86-100%, the
      specificity was 97-99%, and the positive/negative predictive values were 70-92%
      and 99-100%, respectively. No variation according to age was found. Gliadin
      antibodies were determined in 47 children who had well-treated celiac disease.
      Fourteen of these children were also investigated when challenged with gluten.
      Gliadin antibodies (IgA or IgG) decreased significantly in 13 of 13 cases when
      the patients shifted from a gluten-containing diet to a gluten-free one. During
      the gluten challenge, the IgG and IgA increased in 14 of 14 and 11 of 14 cases,
      respectively (two patients suffered from IgA deficiency). In eight patients who
      later appeared to be free of celiac disease, the gliadin antibodies were
      determined on gluten-free diet and during gluten challenge; no significant
      differences in gliadin antibodies were found. We conclude that this test is
      useful in selecting patients with symptoms suggesting celiac disease for a small
      intestinal biopsy. The test seems to be of some value in monitoring the effects
      of a gluten-free diet and during gluten challenge.

PMID- 8271125
TI  - Gastroesophageal reflux and bronchial asthma: prevalence and effect of cisapride
      therapy.
AB  - We evaluated the prevalence of gastroesophageal reflux in 36 children, 22 (61.2%)
      male and 14 (38.8%) female (median age, 75.5 months; range, 18-178), with
      noncontrolled asthma by means of prolonged (22-24 h) esophageal pH monitoring.
      None of the children had gastrointestinal symptoms suggesting gastroesophageal
      reflux. Atopy was seen in 21 of 36 (58.3%) patients. Pathological
      gastroesophageal reflux was present in 27 (75%) children. All patients were given
      cisapride (0.2 mg/kg q.i.d.) for 3 months. A clinical and pharmacological score
      was determined, and a second pH-metric study was made at the end of the follow-up
      period. The following pH-metric parameters were evaluated: the total percentage
      of time pH was < 4, the number of reflux episodes, the number of reflux episodes
      lasting > 5 min, the length of the longest single reflux episode, and the
      percentage of time the esophageal pH was < 4 during sleep. The study was
      completed in 11 of 27 children. The percentage of time that esophageal pH was < 4
      improved in nine of 11 (81.8%) patients (p = 0.013). The percentage of time that
      esophageal pH was < 4 during sleep showed the most significant decrease (p =
      0.002) after treatment. Improvement in both clinical and pharmacological scores
      was highly significant (p < 0.0001) in 19 of 27 patients, eight of whom did not
      want to repeat the pH study. We conclude therefore that gastroesophageal reflux
      is frequently associated with noncontrolled asthma and that medical therapy for
      reflux may improve the further course of respiratory disease.

PMID- 8271126
TI  - Influence of prenatal corticosteroids on bacterial colonization in the newborn
      rat.
AB  - The interactions between bacteria and the host's intestinal barrier appear to be
      important regulators of bacterial colonization. In this study we investigated the
      effect of prenatal corticosteroids, known to accelerate the intestinal maturation
      of newborn rats, on bacterial colonization in the rat pup. Pregnant rats were
      treated with either cortisone acetate or normal saline on days 18-21 of gestation
      and were allowed to deliver spontaneously. The pups, after normal delivery, were
      sacrificed at different times during the first 10 days of life. The entire small
      intestine was removed, and each lumen was flushed to exclude nonadherent,
      transient organisms and homogenized. Tenfold dilutions were plated on horse-blood
      agar (total bacteria) and MacConkey's medium (gram-negatives). Quantitation and
      bacterial typification was determined after 24 h of incubation at 37 degrees C.
      Total bacteria and gram-negatives found in association with the mucosa were
      significantly lower in pups prenatally treated with steroids. These changes were
      not related to any changes in motility or intraluminal digestion. This suggests
      that the developmental condition of the host's intestinal barrier may be an
      important regulator of the bacterial microenvironment of the newborn small
      intestinal mucosa.

PMID- 8271127
TI  - Comparison of methods for estimating fecal carbohydrate excretion in premature
      infants.
AB  - Our previous studies have suggested that there is minimal fecal excretion of
      carbohydrate-derived energy in premature infants fed lactose or glucose-polymer
      as the source of carbohydrate. In these studies, carbohydrate energy excretion
      was equated with the non-nitrogenous, nonfat energy. Although these studies
      provided consistent results, this methodological approach cannot distinguish
      actual excretion of dietary carbohydrate from carbohydrate in the form of large
      molecular compounds derived from infant or bacterial cells (which in fact
      comprise approximately 90% of the measured value). Therefore, in this study we
      compared the absorption of carbohydrate energy to the fractional absorption of
      13C derived from [D-1-13C]-lactose in 10 premature infants 30-32 weeks
      gestational age fed either a commercial premature infant formula containing a
      mixture of carbohydrates (50% lactose: 50% glucose polymer) or the same formula
      in which lactose was the sole carbohydrate. The two methods provided comparable
      estimates of carbohydrate absorption (96 and 94%, respectively), although there
      were significant discrepancies in two infants. These studies provide evidence of
      external validity for the two methods.

PMID- 8271128
TI  - Simple and rapid macronutrient analysis of human milk for individualized
      fortification: basis for improved nutritional management of very-low-birth-weight
      infants?
AB  - Feeding human milk exclusively to the very-low-birth-weight infant may lead to
      insufficient intakes of protein and energy. Although the milk is therefore often
      supplemented with protein and additional calories, there is usually no prior
      information on its macronutrient composition. If such data were available, it
      would be possible to individualize the fortification of the milk. To find simple,
      rapid, and inexpensive methods of enriching it, we evaluated existing
      macronutrient assays of human milk. Thirty frozen samples of early human milk (3
      20 days of lactation) were analyzed for contents of protein (Kjeldahl, Lowry, and
      Bio-Rad protein assays), fat (Folch, total lipids assay, and creamatocrit), and
      carbohydrates (lactose and orcinol assays). The methods were modified to minimize
      cost and time. From these data, we find it appropriate to recommend the use of
      the Lowry (or, alternatively, the Bio-Rad) protein assay, the total lipids assay,
      and the orcinol carbohydrate assay for reasonably accurate determinations of the
      protein and energy contents of human milk. Because the variation in the
      carbohydrate content of human milk is very small, a more simple alternative
      approach would be to include only an average carbohydrate value for an estimate
      of energy content. These low-cost methods can be used in all laboratories
      affiliated to neonatal units taking care of preterm infants. Such individualized
      fortification should serve to further improve the nutritional management of very
      low-birth-weight infants.

PMID- 8271129
TI  - Development of lipolytic activity in gastric aspirates from premature infants.
AB  - Neonates, having little or no pancreatic lipase, would have a compromised ability
      to digest lipids if not for lingual and gastric lipases. To document the
      postnatal developmental profile of preduodenal lipase activity, 350 premature
      infants who were at various gestational ages and who had an orogastric tube had
      their gastric aspirates collected. Two hundred one infants had their gastric
      aspirates collected within 12 h after delivery. Serial collections were performed
      in 25 infants at various postnatal ages. Gastric aspirates collected from
      premature infants had a pH activity profile similar to that of lingual and
      gastric lipase but different from that of pancreatic lipase, indicating that
      their origin was from the tongue and/or stomach. Lipolytic activity and pH of
      these aspirates were quite variable, but no correlation was found between pH and
      enzyme activity. At birth, lipase activity was lower in the younger infants (< or
      = 26 weeks, n = 13). It increased to a peak at 30-32 weeks of gestational age and
      then declined to a lower level at term (> or = 40 weeks, n = 40). Postnatally, a
      composite plot of the serially collected aspirates also showed a predominant peak
      at 28-33 weeks of age. Comparison among siblings in twins (n = 12 pairs) and
      triplets (n = 3) showed great variations in their lipolytic activities,
      suggesting that the hereditary factor is not a major determinant. Various
      combinations of antibiotic medications (ampicillin, cefotaxime, gentamicin, and
      vancomycin) and drugs (dexamethasone, heparin, furosemide, phenobarbital,
      albumin, and vitamin K) apparently had no effect on the level and development of
      gastric lipolytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271130
TI  - Solubility of calcium salts and carrageenan used in infant formulas did not
      influence calcium absorption in rats.
AB  - Calcium absorption from tricalcium phosphate (TCP) was compared to that from
      calcium chloride, CaCl2, in the presence and absence of carrageenan in the rat
      model. There was no difference in percent calcium absorption as indicated by
      femur uptake of TCP or CaCl2 intrinsically labeled with 45Ca given by gavage
      (78.4 +/- 9.6 vs. 80.0 +/- 5.9, respectively). Thus, the difference in solubility
      of the two salts did not influence calcium absorption. When TCP was delivered by
      gavage in a solution containing 1% carrageenan, calcium absorption was not
      decreased compared to that of a control without carrageenan. In this model,
      calcium from TCP in the presence of up to 1% carrageenan is well absorbed.

PMID- 8271131
TI  - Primary sclerosing cholangitis in a child treated by nonsurgical balloon
      dilatation and stenting.

PMID- 8271132
TI  - Fatal cholestatic hepatitis and multisystem failure associated with
      nitrofurantoin.

PMID- 8271133
TI  - Intrahepatic cholestasis in neonatal lupus erythematosus.

PMID- 8271134
TI  - Early steroid therapy for the treatment of giant cell hepatitis with autoimmune
      hemolytic anemia.

PMID- 8271135
TI  - Neonatal sclerosing cholangitis in two siblings: a category of progressive
      intrahepatic cholestasis.

PMID- 8271136
TI  - An infant with ulcerative colitis complicated by endocarditis and cerebral
      infarction.

PMID- 8271137
TI  - Pediatric dyspepsia responsive to oral cromolyn: a report of eleven cases.

PMID- 8271138
TI  - Glutamine-supplemented parenteral nutrition in a child with short bowel syndrome.

PMID- 8271139
TI  - Intestinal spirochaetosis in children.

PMID- 8271140
TI  - T-cell-rich B-cell lymphoma in a child with celiac disease.

PMID- 8271141
TI  - Promising new treatment for type I tyrosinemia.

PMID- 8271142
TI  - Food allergy: the nature of the local gastrointestinal response.

PMID- 8271143
TI  - Betacellulin: newest addition to the epidermal growth factor family.

PMID- 8271145
TI  - Horizontal transmission of HBsAg in children.

PMID- 8271144
TI  - Automatic measurement of the "area under the curve" in the diagnosis of
      gastroesophageal reflux.

PMID- 8271146
TI  - Neonatal hemochromatosis.

PMID- 8271148
TI  - Siblings are important too!

PMID- 8271147
TI  - Alleged health effects of electric or magnetic fields: additional misconceptions
      in the literature.
AB  - Residential or occupational exposures to electric or magnetic fields have been
      reported to be associated with health problems, particularly cancer and
      reproductive mishaps. Misconceptions about these alleged effects continue to be
      published in the medical and scientific literature. Invalid statements relating
      to these effects are challenged in this paper. Case reports and studies dealing
      with exposures to video display terminals, magnetic resonance imaging, microwaves
      from television transmitter facilities, ceiling cable electric heat,
      electromagnetic pulse, power lines, traffic radar units, and other occupational
      exposures are analyzed.

PMID- 8271149
TI  - Siblings and the new baby: changing perspectives.
AB  - Increasingly nurses are called on to provide services to siblings in childbearing
      families. An overview of the broad, interdisciplinary research on siblings and
      newborns that is available to guide nursing practice is provided in this article.
      Studies tend to fit into three categories: (a) sibling responses to the newborn,
      (b) sibling participation in birth, and (c) sibling visiting in the hospital.
      Although nurses may have only short-term contact with families during the
      childbearing cycle, the author emphasizes the importance of having a
      longitudinal, family-oriented understanding of sibling relationships based on
      current research. Suggestions for applying this research to practice during the
      prenatal, intrapartum, and postnatal periods are noted.

PMID- 8271150
TI  - Siblings of hospitalized children: assessment and intervention.
AB  - The issues faced by children who have had a sibling recently hospitalized are
      summarized in this report. In addition, the research findings about this sibling
      experience as well as assessment and intervention strategies for siblings are
      presented. Craft and Knafl and their colleagues have found that the siblings who
      are at the greatest risk for adverse effects are younger and experiencing many
      changes, perceive their parents to be treating them differently as compared with
      before their sibling's hospitalization, have received little information about
      their ill brother or sister, and are being cared for outside of the home by care
      providers who are not relatives. Nurses need to assess siblings and intervene as
      indicated to ensure that the effects of short-term stress do not initiate adverse
      long-term sequelae.

PMID- 8271151
TI  - Perceived stress of nonhospitalized children during the hospitalization of a
      sibling.
AB  - The purpose of this research was to examine nonhospitalized children's
      perceptions of the stress of the hospitalization of a sibling. The subjects were
      45 nonhospitalized children (5-12 years of age), and their parents, who had a
      sibling hospitalized over 24 hours for a medical or surgical condition. The Child
      Drawing: Hospital (CD: H) was used to measure the perception of stress related to
      a sibling's hospitalization. The nonhospitalized children perceived the stress of
      hospitalization at a level of stress (anxiety) equal to the level of stress of
      hospitalized children and higher than children in a school setting found by
      previous investigators. Sex and age were not related to the degree of perceived
      stress (anxiety). The perception of stress varied significantly in relation to
      the type of sibling relationship, residence of the well sibling during the
      hospitalization, frequency of sibling visitation, and amount of parental behavior
      change as identified by the nonhospitalized children.

PMID- 8271152
TI  - Siblings of children with chronic physical and cognitive disabilities.
AB  - During the past 20 years, numerous researchers have examined the effects on well
      children of having a chronically physically and/or cognitively ill/disabled
      sibling. Although the findings are inconsistent and inclusive, the effects of
      this chronic family stress are less than previously thought. This article is a
      summary of studies conducted across the lifespan, highlighting effects on well
      sibling adjustment/well-being, stress and coping, self-concept, sibling
      interactional relationships, parenting, and mediating variables. Sibling
      intervention studies are examined, and nursing implications are presented.

PMID- 8271153
TI  - Mothers' perceptions of sibling adjustment and family life in childhood chronic
      illness.
AB  - Researchers who study the effects of chronic illness on well siblings have
      generally focused on individual characteristics and their relationships with
      psychological adjustment. More recently, researchers suggest that sibling
      adjustment can be best understood within the context of the family. The purpose
      of this study was to examine variations in sibling behavioral adjustment in
      relation to mothers' perceptions of the illness experience and family life. Based
      on mothers' ratings on the behavior problem scale of the Child Behavior Checklist
      (CBCL), five siblings considered poorly adjusted and five very well-adjusted
      siblings were compared with respect to mothers' reports of individual family
      member's response to illness, illness management, parenting philosophy, presence
      of other stressors, availability of social supports, and impact of illness on
      family members and family life. Two major differences were found between mothers
      who rated healthy siblings either poorly or very well adjusted: (a) effects of
      illness on the healthy sibling, the ill child, and the marital relationship and
      (b) perceived controllability of the chronic illness. Devising ways of helping
      mothers feel confident in managing their child's illness is integral to creating
      an environment that promotes optimal development of their ill child and the
      child's siblings.

PMID- 8271154
TI  - Sibling bereavement and grief responses.
AB  - A child's death can have a profound and lasting effect on surviving siblings.
      Early researchers and clinicians have suggested that siblings were at risk for
      serious psychopathology. However, in later studies, researchers found that
      although the grief process was emotionally difficult, siblings may have grown and
      matured as a result of living through the loss. The purpose of this report was to
      review and summarize the literature on sibling bereavement and grief as well as
      to present nursing implications.

PMID- 8271155
TI  - Children's concept of death and sibling death from trauma.
AB  - Factors influencing children's concept of death (their understanding of finality,
      inevitability, and universality) were examined. A bereaved group of 29 siblings
      (5 to 12 years of age) of children who died from trauma were interviewed 13 to 17
      months after their sibling's death. A comparison group (n = 29) of nonbereaved
      siblings who had not experienced a sibling's death was matched for age, race,
      gender, and sociodemographic background. Demographic data, a Piagetian
      developmental assessment, and a concept of death assessment incorporating
      vignettes were used to collect data. The experience of sibling death from trauma
      did not significantly influence acquisition of an accurate concept of death;
      developmental level (p = 0.0001) and age (p = 0.0003) were significant
      predictors. Of the 5-year-old subjects in this study, 45.7% had an accurate
      concept of death, as did > 60% of 6-, 7-, and 8-year-old subjects, 100% of 9-, 11
      , and 12-year-old subjects, and 90% of 10-year-old subjects. This reflects an
      understanding of death at a much younger age than reported by previous
      researchers.

PMID- 8271156
TI  - American children and immunizations: Part I, How bad is it?

PMID- 8271157
TI  - Survey of mycoflora and mycotoxins in Egyptian soybean seeds.
AB  - After four months in commercial storage, 100 soybean samples from different
      places of Egyptian Governorates were assayed for filamentous fungal growth at two
      incubation temperatures (28 and 45 degrees C). 73 species and 8 varieties
      belonging to 32 genera were isolated by the dilution plate method. At 28 degrees
      C, the common species were Aspergillus flavus, A. fumigatus, A. niger and A.
      alutaceus, followed by A. terreus, Penicillium chrysogenum, P. citrinum, Mucor
      hiemalis, M. racemosus, Emericella nidulans, Rhizopus stolonifer, Nectria
      haematococca and Scopulariopsis brevicaulis. At 45 degrees C, A. fumigatus was
      the dominant species followed by Rhizomucor pusillus, Emericella nidulans and
      Neosartorya fischeri. Penicillium which was one of the most abundant genus at 28
      degrees C, absent at 45 degrees C. The seeds were assayed for aflatoxin,
      ochratoxin A, sterigmatocystin, T-2 and zearalenone by thin layer chromatographic
      analysis. Aflatoxin was detected in 35% of soybean seed samples (5-35
      micrograms/kg). The other mycotoxins were not detected.

PMID- 8271158
TI  - Rapid identification and differentiation of yeasts by DNA and PCR fingerprinting.
AB  - We have used the techniques of DNA fingerprinting and polymerase chain reaction
      (PCR) with probes specific for hypervariable repetitive DNA sequences (mini- and
      microsatellite DNAs) to analyze 36 yeast strains belonging to 10 species and 2
      genera. Using (GTG)5, (GACA)4, phage M13 DNA and the M13 sequence GAGGGTGGCGGTTCT
      as probes and primers, respectively, we obtained DNA polymorphisms which allowed
      us to discriminate 23 biotechnologically important strains of the yeast
      Saccaromyces cerevisiae and to distinguish them from strains of S. pastorianus,
      S. bayanus and S. willianus. Our results demonstrate that both DNA and PCR
      fingerprinting are suitable tools for an easy, fast and reliable molecular typing
      of yeasts. The DNA fingerprinting method seems to be more sensitive than PCR
      fingerprinting with respect to the individualization of strains. Nevertheless,
      using the PCR fingerprinting technique we were able to unambigously discriminate
      between genotypes of different species. Therefore, PCR fingerprinting might
      become a useful tool in the classification of yeasts on the basis of phylogenetic
      relatedness.

PMID- 8271159
TI  - Extracapsular cataract surgery, retinal detachment, and YAG laser posterior
      capsulotomy.

PMID- 8271160
TI  - Epidemiology of retinal detachment following extracapsular cataract extraction: a
      follow-up study with an analysis of risk factors.
AB  - We reviewed the medical records of 1,726 eyes consecutively operated on with
      extracapsular cataract extraction to examine the incidence of and the risk
      factors for retinal detachment (RD). In Denmark, both diagnoses and deaths are
      registered centrally; therefore, a complete follow-up was achieved in each case
      and actuarial statistical methods were used in the risk assessment. Seven eyes
      (0.41%) developed RD and 345 eyes (20.0%) had YAG-laser capsulotomy in the
      observation period, which averaged 39 months. We identified the following risk
      factors for RD: age less than 70 years at the time of surgery, intraoperative
      complications, axial length > or = 25 mm. Nonsignificant factors included male
      gender and postoperative complications. One eye (0.29%) developed RD following
      YAG-laser capsulotomy. We concluded that the high risk of RD is concentrated in a
      small group of myopic patients who have cataract surgery when they are less than
      70 years of age. Our results do not suggest a causal relationship between YAG
      laser capsulotomy and subsequent RD.

PMID- 8271161
TI  - Effect of anterior capsulotomy on decentration of a two-zone multifocal
      intraocular lens.
AB  - A study was undertaken to determine if can-opener (CO) or continuous curvilinear
      capsulorhexis (CCC) anterior lens capsulotomy influences decentration of a two
      zone multifocal intraocular lens (IOL). Fifty IOLs (25 with polypropylene haptics
      and 25 with poly[methyl methacrylate] haptics) were implanted following CO, 42
      with poly(methyl methacrylate) haptics, following CCC. The extent and direction
      of decentration was estimated using a photogeometric technique. The haptic
      material may influence decentration. Continuous curvilinear capsulorhexis was
      associated with less decentration than CO (0.36 mm and 0.43 mm, respectively).
      The difference, however, was not statistically significant.

PMID- 8271162
TI  - Depth of focus and functional results in patients with multifocal intraocular
      lenses: a long-term follow-up.
AB  - We did a follow-up study of 35 patients who had phacoemulsification with
      implantation of diffractive, multifocal intraocular lenses (IOLs) 2.5 years ago.
      The patients had an average age of 58.2 +/- 9.6 years. Fifty multifocal IOLs were
      implanted (3M 815LE, n = 45; 3M 825X, n = 5). Refractive values, visual acuity,
      depth of focus, and the dependence on corrective glasses were evaluated. Eighty
      percent of the spherical equivalents ranged from -1 to +1 D (mean 0.25 +/- 0.71).
      In 76% the cylindric power was not higher than 1 D (mean 0.87 +/- 0.64). With
      distance correction, 100% of the patients achieved a visual acuity of 20/40 or
      better. Without correction, 86% achieved 20/40 or better. Near acuity of 20/40 or
      better with only distance correction was achieved in 98% of patients. Ninety-four
      percent had a near acuity of 20/40 or better without any correction. The depth of
      focus was significantly better in the multifocal group than in a control group of
      patients with monofocal IOLs (P < .01). Although 90% of the patients had good
      uncorrected visual acuity results of 20/40 or better for near and distance, 58%
      preferred glasses for distance and/or near.

PMID- 8271163
TI  - Undesired light images associated with ovoid intraocular lenses.
AB  - Ovoid intraocular lenses (IOLs) accounted for approximately 35% of the lenses
      implanted in 1991. Despite their popularity among surgeons, patient observations
      and complaints suggest that ovoid lenses are associated with undesired optical
      images postoperatively. A pilot clinical study was carried out to test that
      hypothesis. A multicentered investigation of 289 cases with well-centered IOLs
      determined that 45% of 168 patients with ovoid lenses observed unwanted optical
      phenomena at some time after surgery, whereas 17% of 121 patients with round IOLs
      had similar complaints. Based upon the preliminary clinical study a laboratory
      investigation was designed to assess optical performance differences between
      ovoid and round IOLs. One testing system used scatterometry and a second, ray
      tracing analysis. Both methods determined that the truncated, thickened edge of
      ovoid lenses was associated with significant light scattering, possibly
      accounting for the extraneous light images observed by some patients. The results
      of the clinical and laboratory investigations suggest that undesired optical
      images produced by ovoid IOLs are due to lens shape rather than to the reduced
      dimension of the optic.

PMID- 8271164
TI  - Phacoemulsification, capsulorhexis, and intraocular lens power prediction
      accuracy.
AB  - Phacoemulsification with capsulorhexis reduces the surgical variability and may
      result in a more predictable refractive outcome. To evaluate the prediction
      accuracy with current IOL power prediction formulas, we reviewed a retrospective
      series of 628 phacoemulsification cases, including 148 short (< 22 mm) and 80
      long (> 25 mm) eyes. Using the Binkhorst II formula and the manufacturer's
      recommended anterior chamber depth (ACD) values, the mean absolute refractive
      prediction error was 0.56 diopters (D). This error could be reduced to 0.51 D by
      retrospectively optimizing the ACD values for each lens type. Under similar least
      error conditions, the mean error was 0.51 D with the SRK/T formula and 0.47 D
      with the Olsen formula (P < .01). The Binkhorst formula overestimated the
      refraction in short eyes and underestimated the refraction in long eyes. The
      SRK/T and the Olsen formula were unbiased with the axial length. We hypothesize
      that the high prediction accuracy may be partially explained by a more
      predictable pseudophakic ACD with the current surgical technique.

PMID- 8271165
TI  - The Hoffer Q formula: a comparison of theoretic and regression formulas.
AB  - A new formula, the Hoffer Q, was developed to predict the pseudophakic anterior
      chamber depth (ACD) for theoretic intraocular lens (IOL) power formulas. It
      relies on a personalized ACD, axial length, and corneal curvature. In 180 eyes,
      the Q formula proved more accurate than those using a constant ACD (P < .0001)
      and equal (P = .63) to those using the actual postoperative measured ACD (which
      is not possible clinically). In 450 eyes of one style IOL implanted by one
      surgeon, the Hoffer Q formula was equal to the Holladay (P = .65) and SRK/T (P =
      .63) and more accurate than the SRK (P < .0001) and SRK II (P = .004) regression
      formulas using optimized personalization constants. The Hoffer Q formula may be
      clinically more accurate than the Holladay and SRK/T formulas in eyes shorter
      than 22.0 mm. Even the original nonpersonalized constant ACD Hoffer formula
      compared with SRK I (using the most valid possible optimized personal A-constant)
      has a better mean absolute error (0.56 versus 0.59) and a significantly better
      range of IOL prediction error (3.44 diopters [D] versus 7.31 D). The range of
      error of the Hoffer Q formula (3.59 D) was half that of SRK I (7.31 D). The
      highest IOL power errors in the 450 eyes were in the SRK II (3.14 D) and SRK I
      (6.14 D); the power error was 2.08 D using the Hoffer Q formula. The series using
      overall personalized ACD was more accurate than using an axial length subgroup
      personalized ACD in each axial length subgroup. The results strongly support
      replacing regression formulas with third-generation personalized theoretic
      formulas and carefully evaluating the Holladay, SRK/T, and Hoffer Q formulas.

PMID- 8271166
TI  - An improved universal theoretical formula for intraocular lens power prediction.
AB  - Although available empirically derived and theoretical formulas perform
      adequately for eyes of average axial length, both have been shown to be deficient
      for eyes that have unusually short and long axial lengths. I developed a formula
      based on a theoretical model eye in which anterior chamber depth is related to
      axial length and keratometry. A relationship between the A-constant and a "lens
      factor" is also used to determine anterior chamber depth. The location of the
      intraocular lens' principle planes of refraction is retained as a relevant
      variable in the formula, and the user need not know the material and construction
      of the lens and or its constant. I compared the new formula with the SRK II,
      Holladay, and SRK/T formulas in a group of 100 unselected patients and in
      selected subgroups of patients with average, short, and long axial lengths. The
      new formula was significantly more accurate than the other third-generation
      formulas and maintained its accuracy in the subgroups. The formula can be
      described as universal because it can be used for different lens styles and for
      eyes with short, medium, and long axial lengths.

PMID- 8271167
TI  - Postoperative complications of capsulorhexis.
AB  - Capsulorhexis has become the preferred method of anterior capsulotomy, and
      untoward effects have not been frequently noted. Nevertheless, distinct
      complications of continuous tear anterior capsulotomy are now recognized. These
      include capsular bag hyperdistention, shrinkage of the anterior capsule opening
      with visual loss and/or intraocular lens decentration, and lens epithelial cell
      hyperproliferation on the posterior lens capsule. The latter has not been
      reported and may be associated wit reduction or closure of laser posterior
      capsulotomies in the form of a "string of pearls" around the capsule opening.
      Current styles of capsular surgery and intraocular lens implantation in which the
      anterior capsule edge overlaps the lens may be responsible for these phenomena.
      Although altering the surgical methods may obscure these complications,
      eliminating the anterior subcapsular and equatorial lens epithelial cells is
      necessary to prevent capsule contraction and lens epithelial cell
      hyperproliferation.

PMID- 8271168
TI  - Corneal endothelial and intraocular pressure changes after phacoemulsification
      with Amvisc Plus and Viscoat.
AB  - A prospective, randomized, observer-marked study was conducted to compare corneal
      endothelial and intraocular pressure (IOP) changes after cataract surgery with
      the viscoelastic agents Amvisc Plus and Viscoat. Forty-nine patients (50 eyes)
      who had uncomplicated phacoemulsification and implantation of a posterior chamber
      intraocular lens were randomly assigned to either Amvisc Plus (25 eyes) or
      Viscoat (25 eyes) groups. Surgical technique was rigidly standardized in all
      cases. No significant difference in endothelial parameters or postoperative IOPs
      measured at 24 hours, one week, and two months was detected by analysis of
      variance between the Amvisc Plus and the Viscoat groups. Visualization was
      difficult with Viscoat because of its tendency to retain bubbles.
      Phacoemulsification energy was related to a loss of endothelial density,
      regardless of the viscoelastic used. The postoperative beta blocker may have
      contributed to the lower average postoperative IOP than has been reported.

PMID- 8271169
TI  - Intraocular miotics and postoperative inflammation.
AB  - Sixty patients scheduled for planned extracapsular cataract extraction with
      intraocular lens (IOL) implantation were randomly assigned to receive
      acetylcholine chloride, carbachol, or balanced salt solution (BSS) immediately
      after IOL placement and at the end of the surgical case. As part of the
      postoperative evaluation, patients were examined at the first and eighth
      postoperative day with a Kowa FC-1000 laser flare and cell meter to assess
      objectively the amount of postoperative inflammation. At day one and day eight,
      the amount of cell and flare in the carbachol group was significantly greater
      than in the acetylcholine group or in the BSS control group. The acetylcholine
      group had significantly less flare than the BSS group at day one; yet there was
      no difference between the two groups at day eight, nor was there a significant
      difference in the amount of cells between day one and day eight. It is presumed
      that the prolonged miosis seen in the carbachol group delays the re-establishment
      of the blood-aqueous barrier after surgery, causing the inflammatory response.

PMID- 8271170
TI  - Restoring lens capsule integrity enhances lens regeneration in New Zealand albino
      rabbits and cats.
AB  - In studies conducted by numerous investigators for 150 years, lenses regenerated
      following endocapsular lens extraction in New Zealand albino rabbits have been
      irregular in shape, appearing primarily doughnut-shaped as a result of lack of
      lens growth at the site of the anterior capsulotomy and its adhesion to the
      posterior capsule. In the present study, we restored the lens capsule integrity
      by inserting a collagen patch at the time of surgery to seal the anterior
      capsulotomy and to improve the shape and structure of the regenerated lenses. We
      then filled the capsule bag with air to prevent adhesions between the anterior
      and posterior capsule and maintain capsule tautness and shape. Lens regeneration
      was first noted as early as one to two weeks. Regenerated lens filled
      approximately 50% of the capsule bag at two weeks and 100% by five weeks.
      Subsequent growth was in the anterior-posterior direction and measured by A-scan
      biometry. Lens thickness increased by 0.3 mm per month. The regenerated lenses
      were spherical with normal cortical structure and a nuclear opacity. In
      conclusion, restoration of lens capsular integrity with a collagen patch
      following endocapsular lens extraction enhanced the shape, structure, and growth
      rate of the regenerated lenses. In addition, lens regeneration was shown to occur
      in two cats.

PMID- 8271171
TI  - Temporary keratoprosthesis for transscleral fixation of posterior chamber
      intraocular lenses with penetrating keratoplasty.
AB  - In the absence of zonular and capsular support, cataract surgeons increasingly
      prefer suture-fixated posterior chamber intraocular lenses (IOLs) to angle
      supported anterior chamber lenses as a secondary IOL. Various suturing techniques
      have been proposed for fixating the posterior chamber IOL. Transscleral suture
      fixation appears advantageous but problematic when performed on an open globe.
      Moreover, excision of the vitreous base is impeded by the iris and the dark,
      unstable image. This article describes a technique that takes advantage of a
      temporary keratoprosthesis (TKP). When sutured onto the trephination opening, the
      TKP provides a bright, stable image and permits peripheral indentation of the
      globe, allowing for controlled, thorough vitrectomy. With the infusion pressure
      supplying adequate eye tone, ab externo transfixation, and thus a targeted
      passage of the sulcus, is possible. If the cornea permits transfixation, TKP may
      be used to tamponade after trephination and as a lens rest while the surgeon ties
      the sutures to the haptics.

PMID- 8271172
TI  - Reduced bacterial adhesion to heparin-surface-modified intraocular lenses.
AB  - Bacterial adherence to intraocular lenses (IOLs) could be the cause of
      endophthalmitis following cataract surgery and lens implantation. There are
      previous reports that heparin bound to the surface of poly(methyl methacrylate)
      (PMMA) IOLs reduces cell adhesion. In this study, the in vitro adherence of
      Staphylococcus epidermidis, Staphylococcus aureus, and Pseudomonas aeruginosa to
      regular PMMA IOLs and to heparin-surface-modified (HSM) PMMA IOLs was
      investigated. The three bacterial strains attached in significantly lower numbers
      to HSM-PMMA IOLs than to PMMA IOLs (P < .01). Heparin in solution also inhibited
      attachment of Staphylococcus epidermidis to regular PMMA IOLs. Heparin may reduce
      adherence by placing a highly hydrated layer between the bacteria and the IOL
      surface. Therefore, the use of HSM-PMMA IOLs could diminish the incidence of
      endophthalmitis.

PMID- 8271173
TI  - Heparin-modified lenses for eyes at risk for breakdown of the blood-aqueous
      barrier during cataract surgery.
AB  - To determine the appropriateness of heparin-surface-modified (HSM) lenses in eyes
      at risk for breakdown of the blood-aqueous barrier, 36 consecutive patients with
      cataracts associated with chronic recurrent or past uveitis had extracapsular
      cataract extraction and insertion of an HSM posterior chamber one-piece
      intraocular lens (IOL). Examinations for implant precipitates (IPs), fibrin
      membranes, IOL synechias, and visual outcome were done postoperatively. Results
      show that despite a recurrence of overt uveitis with keratic precipitates in 13
      eyes (36.1%), IPs were seen in only six eyes (16.6%) and were generally small and
      few in number. An acute postoperative fibrin reaction, which is related to blood
      aqueous barrier breakdown, occurred in nine eyes. Implant synechias were found in
      three eyes. We found that HSM provided a cell-free IOL surface in the majority of
      eyes at high risk for blood-aqueous barrier breakdown and uveitis. Heparin
      surface modification does not prevent complications but tends to protect the IOL
      from inflammation changes that might otherwise occur.

PMID- 8271174
TI  - Comparison of the optical and visual quality of poly(methyl methacrylate) and
      silicone intraocular lenses.
AB  - We evaluated experimentally the optical quality of poly(methyl methacrylate)
      (PMMA) (Storz 68UV, AMO PC58) and silicone (AMO SI19, Adatomed 90D) intraocular
      lenses (IOLs) and compared the results with our clinical data. We measured
      surface and image quality using the Zygo laser interferometer and modulation
      transfer function (MTF) using the Ealing EROS MTF analyzer. Contrast acuity was
      tested clinically with glare and without glare (Regan charts); AMO PC58, n = 18;
      AMO SI19, n = 7; Adatomed 90D, n = 18). Modulation transfer function and image
      quality were slightly better with PMMA IOLs but the reduction of MTF with
      silicone lenses was within the 1/8 diopter defocus range. Surface quality of
      silicone IOLs was superior to that of PMMA IOLs. Contrast acuity measured
      clinically was also slightly better with PMMA IOLs at low contrast and with glare
      but differences were not significant. Our results suggest that optical and visual
      quality of silicone IOLs is slightly lower than with PMMA IOLs. Experimental and
      clinical results correlated closely. However, the small differences observed are
      unlikely to be significant clinically.

PMID- 8271175
TI  - Experimental study of small intraocular lenses using an eye model.
AB  - Contrast and glare tests were performed on small intraocular lenses (IOLs) using
      a new eye model, which was based on and about the same size as the Gullstrand eye
      model. Lenses with a small optic diameter were inserted and retinal images were
      observed under the operating microscope. Contrast and glare disability tests were
      done using the MCT-8000 contrast tester and the Miller-Nadler glare tester. No
      effect on contrast sensitivity attributable to glare was observed, but under
      severe glare light conditions a faint reflection around the circumference of the
      optic was found. Questionnaires from patients implanted with small optic IOLs
      confirmed that this phenomenon was similar to their symptoms.

PMID- 8271176
TI  - Implanting two posterior chamber intraocular lenses in a case of microphthalmos.
AB  - A 31-year-old male with bilateral microphthalmos and a history of severe
      refractive amblyopia presented with early nuclear sclerosis. Intraocular lens
      calculations determined the patient would need about a 46.0 diopter power
      intraocular lens in both eyes to achieve satisfactory vision postoperatively.
      When no manufacturer could or was willing to make such a high-power lens, we
      chose to implant two lenses in each eye. The patient is satisfied with his
      postoperative vision and overall outcome.

PMID- 8271177
TI  - Phacoemulsification after T-hex keratotomy.
AB  - T-hex keratotomy surgically corrects manifest hyperopia. The typical patient
      presenting for this surgery is a presbyope who develops symptoms from latent
      hyperopia. These patients are older than typical radial keratotomy patients and
      are thus likely to develop senile cataracts sooner. The exact surgical approach
      to cataract surgery in such patients is unknown. We report a patient who had
      successful cataract extraction by phacoemulsification with implantation of a
      posterior chamber lens after a previous routine T-hex keratotomy. The
      preoperative workup and the surgical technique did not require modification.

PMID- 8271178
TI  - Brown-Mclean syndrome associated with corneal endotheliitis in a pseudophakic
      eye.
AB  - A healthy 65-year-old woman had uncomplicated unilateral extracapsular cataract
      extraction followed by iridocapsular intraocular lens (IOL) implantation. Three
      and one half years after surgery, the inferior cornea developed marked edema with
      moderate retrocorneal precipitates, a phenomenon that recurred three more times
      during her eight-year postoperative course. Values obtained by laser flare cell
      meter coincided with each recurrence of corneal edema. Each occurrence was
      managed well by steroid therapy. Corneal endothelial cell density of the affected
      eye changed from a presurgical value of 3,260 cells/mm2 (central) to 553 (upper),
      519 (central), and 363 (inferior). The intraocular lens was not touching the
      cornea, and there were no signs of general and local herpetic infections. The
      recurrent corneal edema responded well to steroid therapy, suggesting concurrent
      corneal endotheliitis and Brown-Mclean syndrome.

PMID- 8271179
TI  - Ocular axial length changes in a pediatric patient with aphakia and pseudophakia.
AB  - Excessive eye elongation can be induced in experimental animals by visual
      deprivation. A tendency toward myopic refraction or shift in pediatric aphakia
      has been recorded in some children. In this report, we present the case of an 18
      year-old patient who had developmental cataracts treated at seven years of age
      with bilateral cataract extraction and implantation of an intraocular lens in one
      eye only. Axial length of the eye with a contact lens increased compared with the
      eye with the intraocular lens.

PMID- 8271180
TI  - Continuous sheet of lens epithelium on an intraocular lens: pathological
      confirmation of specular microscopy.
AB  - A monolayer of proliferating lens epithelium on the anterior surface of an
      intraocular lens was found cytologically and confirmed histologically in a
      postmortem examination of one eye of a 57-year-old man. The man had had
      extracapsular cataract surgery five years earlier. This pathological finding
      confirms observations with specular microscopy.

PMID- 8271181
TI  - Enlarging the pupil for cataract extraction using flexible nylon iris retractors.
AB  - A technique using flexible iris retractors to manage small pupils during cataract
      extraction reduces iris trauma, allows adjustment of pupil size, and reduces
      intraoperative difficulty more than previously described techniques. This method
      is appropriate for extracapsular cataract extraction and phacoemulsification, as
      well as the posterior segment procedures for which it was originally described.

PMID- 8271182
TI  - Crack and flip phacoemulsification technique.
AB  - The crack and flip phacoemulsification technique combines the advantages of
      circumferential division of the nucleus and nucleofactis techniques. As such, it
      adds safety and control to the procedure. We describe each of the surgical
      maneuvers, including machine settings, and explain the rationale for maneuvers
      and machine settings.

PMID- 8271183
TI  - Consultation section. A 75-year-old female had a trabeculectomy performed for
      open-angle glaucoma in her right eye.

PMID- 8271184
TI  - Evaluating astigmatic results.

PMID- 8271185
TI  - Origin of the scleral tunnel method.

PMID- 8271186
TI  - Acute intraoperative suprachoroidal hemorrhage.

PMID- 8271187
TI  - Residual error from correcting cylinders.

PMID- 8271188
TI  - New formula for vector change in astigmatism.

PMID- 8271189
TI  - Delayed postoperative reaction from pigment dispersion syndrome.

PMID- 8271190
TI  - Qualitative keratoscopy at the slitlamp in postkeratoplasty suture adjustment.

PMID- 8271191
TI  - Modified needle and a "one-port plus" approach for ciliary sulcus fixation of a
      dislocated IOL.

PMID- 8271192
TI  - Advantage of marcaine for topical anesthesia.

PMID- 8271193
TI  - Changes of intracellular pH in rat mesenteric vascular smooth muscle with high-K+
      depolarization.
AB  - 1. In mesenteric vascular smooth muscle cells changes in extracellular pH are
      rapidly transmitted to the cytoplasm. The mechanism involved is unknown, but it
      may be due to a high proton permeability of the surface membrane, in which case
      changes in membrane potential would alter the driving force for proton entry. We
      have therefore examined the voltage sensitivity of intracellular pH (pHi) in
      these cells. 2. Strips of mesenteric resistance vessels were loaded with SNARF-1
      to monitor pHi and tension was simultaneously measured. Tissues were superfused
      with oxygenated solutions at 37 degrees C and pH 7.4. Isosmotic substitution of
      K+ for Na+ was used to depolarize the preparations. 3. pHi was found to be
      sensitive to alteration of [K+]. Depolarization of the tissue with K+ caused
      contraction and produced transient increases in pHi. When pHi regulation was
      blocked there was no significant change in the size of the alkalinization induced
      by high K+, thus it is unlikely that the results can be explained by voltage
      sensitivity of pHi regulating mechanisms. 4. In nominally Ca(2+)-free solution,
      the tissue does not contract and the alkalinization with high K+ was
      significantly greater than that occurring in 3 mM Ca2+. 5. There was a rapid
      acidification, when pHi regulation was blocked, which is consistent with a high
      proton permeability. 6. The effects of membrane potential on pHi have been
      modelled and show that they can be accounted for by effects of voltage on H+
      influx through a proton channel. The effects of changing external pH on H+ influx
      also fit the model. Estimation of the proton permeability gave a high value (0.4
      cm s-1). 7. The results presented demonstrate (i) a voltage sensitivity of pHi in
      mesenteric vascular smooth muscle cells and (ii) a particularly high permeability
      of the membrane to protons. The physiological significance of these findings is
      discussed.

PMID- 8271194
TI  - Membrane potential, resting calcium and calcium transients in isolated muscle
      fibres from normal and dystrophic mice.
AB  - 1. Single skeletal muscle fibres were enzymatically isolated from the flexor
      digitorum brevis muscles (FDB) of dystrophic mdx and control C57BL/10 mice aged 3
      9 weeks. In this age range the majority (> 95%) of the mdx fibres were
      morphologically normal. 2. There was no significant difference between the
      resting membrane potential (RMP) of mdx and control mice, -71.2 +/- 1.21 (n = 26)
      and -70.6 +/- 1.15 mV (n = 42), respectively. 3. At RMP more negative than -60 mV
      the resting calcium (recorded with fura-2, free acid ionophoresed into cell) in
      the dystrophic mdx cells was not significantly different from the normal animals,
      45.7 +/- 4.1 (n = 10) and 46.2 +/- 3.9 nM (n = 9), respectively. 4. The resting
      cytosolic calcium concentration was measured simultaneously with the RMP. At RMP
      between -60 to -17 mV there was an increase in the resting calcium concentration
      in both mdx and control ranging from 79.3 to 252 nM. This increase was most
      probably due to the activation of the slow calcium current. 5. Fura-2 calcium
      transients were produced via single action potential stimulation using an
      intracellular microelectrode both to stimulate the cell and record potential
      changes. There was no significant difference between the rise time (Tp) or half
      decay time (T1/2) at 22 degrees C of the calcium transient in response to a
      single action potential in mdx compared to normal animals, 5.9 +/- 0.34 (n = 8)
      and 5.4 +/- 0.36 ms (n = 7); 39.5 +/- 2.9 (n = 8) and 40.75 +/- 3.7 ms (n = 7),
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271195
TI  - Indomethacin reduces acute baroreceptor resetting in the dog.
AB  - 1. The influence of local perfusion of the carotid sinus with the cyclo-oxygenase
      blocker indomethacin on acute baroreceptor resetting was investigated in
      anaesthetized dogs. 2. The carotid sinus was isolated and perfused with
      oxygenated Krebs-Henseleit solution. Single units from the carotid sinus nerve
      were recorded. The carotid sinus was conditioned with static pressures of 50, 100
      and 150 mmHg for 15 min. Following the conditioning period a carotid sinus
      pressure (CSP)-discharge curve was constructed using static stepwise increases in
      CSP. 3. Perfusion of the carotid sinus with indomethacin (20 microM) caused an
      elevation in the threshold at every conditioning pressure (96.8 +/- 4.8 vs. 83.8
      +/- 4.1 mmHg for 100 mmHg, P < 0.01; 91.9 +/- 4.7 vs. 70.3 +/- 4.4 mmHg for 50
      mmHg, P < 0.01; and 103.5 +/- 4.4 vs. 96.4 +/- 4.1 mmHg for 150 mmHg, P = 0.06,
      respectively) and a significant reduction in the peak discharge rate at each
      conditioning pressure (32.0 +/- 4.4 vs. 48.2 +/- 5.5 spikes/s for 100 mmHg, P <
      0.01; 32.2 +/- 5.8 vs. 45.8 +/- 5.1 spikes/s for 50 mmHg, P < 0.01; 32.0 +/- 3.7
      vs. 51.1 +/- 8.1 spikes/s for 150 mmHg, P < 0.01). The resetting ratio (change in
      threshold/change in conditioning CSP) for both downward resetting (conditioning
      CSP from 100 to 50 mmHg) and upward resetting (conditioning CSP from 100 to 150
      mmHg) was significantly decreased after indomethacin (0.10 +/- 0.02 vs. 0.27 +/-
      0.02 for downward resetting, P < 0.01 and 0.14 +/- 0.03 vs. 0.25 +/- 0.01 for
      upward resetting, P < 0.01, respectively). 4. Conversely, perfusion of the
      carotid sinus with arachidonic acid (20 microM) significantly decreased the
      threshold at each conditioning CSP and increased the peak discharge rate at each
      conditioning CSP. The resetting ratio was significantly increased after
      arachidonic acid. 5. There was no change in resting carotid diameter or in the
      carotid sinus pressure-carotid diameter relationship after indomethacin or
      arachidonic acid. 6. Removal of the endothelial cells in the carotid area with
      saponin did not prevent the effects of indomethacin on baroreceptor resetting. 7.
      These results suggest that prostaglandins have a tonic effect on the activity of
      the carotid sinus baroreceptor and may play a role in acute baroreceptor
      resetting.

PMID- 8271196
TI  - On the mechanism of M-current inhibition by muscarinic m1 receptors in DNA
      transfected rodent neuroblastoma x glioma cells.
AB  - 1. Acetylcholine (ACh) produces two membrane current changes when applied to
      NG108-15 mouse neuroblastoma x rat glioma hybrid cells transformed (by DNA
      transfection) to express m1 muscarinic receptors: it activates a Ca(2+)-dependent
      K+ conductance, producing an outward current, and it inhibits a voltage-dependent
      K+ conductance (the M conductance), thus diminishing the M-type voltage-dependent
      K+ current (IK(M)) and producing an inward current. The present experiments were
      undertaken to find out how far inhibition of IK(M) might be secondary to
      stimulation of phospholipase C, by recording membrane currents and intracellular
      Ca2+ changes with indo-1 using whole-cell patch-clamp methods. 2. Bath
      application of 100 microM ACh reversibly inhibited IK(M) by 47.3 +/- 3.2% (n =
      23). Following pressure-application of 1 mM ACh, the mean latency to inhibition
      was 420 ms at 35 degrees C and 1.79 s at 23 degrees C. Latencies to inhibition by
      Ba2+ ions were 148 ms at 35 degrees C and 92 ms at 23 degrees C. 3. The
      involvement of a G-protein was tested by adding 0.5 mM GTP-gamma-S or 10 mM
      potassium fluoride to the pipette solution. These slowly reduced IK(M), with half
      times of about 30 and 20 min respectively, and rendered the effect of
      superimposed ACh irreversible. Effects of ACh were not significantly changed
      after pretreatment for 24 h with 500 ng ml-1 pertussis toxin or on adding up to
      10 mM GDP-beta-S to the pipette solution. 4. The role of phospholipase C and its
      products was tested using neomycin (to inhibit phospholipase C), inositol 1,4,5
      trisphosphate (InsP3) and inositol 1,3,4,5-tetrakisphosphate (InsP4), heparin,
      and phorbol dibutyrate (PDBu) and staurosporin (to activate and inhibit protein
      kinase C respectively). Both neomycin (1 mM external) and InsP3 (100 microM
      intrapipette) inhibited the ACh-induced outward current and/or intracellular Ca2+
      transient but did not block ACh-induced inhibition of IK(M). Intrapipette heparin
      (1 mM) blocked activation of IK(Ca) and reduced Ach-induced inhibitions of IK(M),
      but also reduced inhibition of ICa via endogeneous m4 receptors. PDBu (with or
      without intrapipette ATP) and staurosporin had no significant effects.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8271197
TI  - Transducer properties of the rapidly adapting stretch receptor neurone in the
      crayfish (Pacifastacus leniusculus).
AB  - 1. The transducer properties of the rapidly adapting stretch receptor neurone of
      the crayfish (Pacifastacus leniusculus) were studied using a two-microelectrode
      voltage clamp technique. 2. The impulse response to ramp-and-hold extensions of
      the receptor muscle typically consisted of a high frequency burst followed by
      cessation of impulses within a relatively short time depending on the amplitude
      of extension. The type of adaptation was consistent with earlier studies. The
      stimulus-response relationship for the impulse frequency was non-linear and had a
      slope in a log-log plot of 2.9. 3. When impulse generation was blocked by
      tetrodotoxin (TTX), (block of Na+ channels) the receptor potential was extension
      dependent and similar to that found in the slowly adapting receptor. For small
      extensions there was an initial peak followed by a fall to a steady potential
      level. For large extensions the potential response during the ramp phase
      consisted of a peak followed by a constant potential level lasting to the end of
      the ramp. When the extension changed to the hold phase the potential fell towards
      a steady state. The relation between extension and amplitude of receptor
      potential was non-linear and saturated at -40 to -30 mV (extensions > 15% of zero
      length, lo). 4. When potassium channels were blocked by TEA (50 mM) and 4
      aminopyridine (4-AP, 5 mM) (and Na+ channels blocked by TTX) the shape of the
      generator potential become less complex with an increased amplitude for large
      extensions. 5. When the receptor neurone was voltage clamped at the resting
      potential, extension of the receptor muscle produced an inwardly directed
      receptor current, the stretch-induced current (SIC). The response consisted of a
      fast transient phase which decayed towards a steady state. The SIC peak amplitude
      was dependent on extension in a sigmoidal fashion and saturated at 190 nA
      (extensions > 25% of lo). The slope of the steepest part of the stimulus-response
      relation (between 10 and 20% extension) was 4.7 +/- 0.25 (mean +/- S.E.M.) in a
      log-log plot. 6. The peak amplitude of the SIC increased with increasing
      extension speed (ramp steepness), the relation between the slope of the ramp and
      current amplitude being a first order (hyperbolic) function. The amplitude of the
      receptor current was voltage dependent and had a reversal potential of +16.2 +/-
      1.8 mV (mean +/- S.E.M., 32 cells). From the reversal potential the permeability
      ratio, PNa/PK, of the transducer permeability system was calculated to be 1.5.
      The I-V curve of SIC was non-linear.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271198
TI  - An in vitro study of the properties of single vagal afferents innervating guinea
      pig airways.
AB  - 1. A novel preparation of the trachea and main bronchi with attached vagus nerve
      from the guinea-pig maintained in vitro was used to study the properties of
      single vagal afferent nerve fibres with identified receptive fields. 2.
      Recordings were made from twenty-eight C fibres with a mean conduction velocity
      of 0.9 +/- 0.1 m s-1 and twenty-four A delta fibres with a mean conduction
      velocity of 8.4 +/- 1.3 m s-1. Receptive fields for C and A delta fibres were of
      small diameter, distributed throughout the trachea and right bronchus and
      possessed very low mechanical thresholds of 2.2 +/- 0.4 and 1.1 +/- 0.3 mN
      respectively. 3. The chemosensitivity of isolated afferents was studied by
      applying drugs directly onto identified receptive fields. A delta fibres were
      insensitive to capsaicin (up to 3 microM), bradykinin (3 microM), histamine (10
      microM) and 5-hydroxytryptamine (5-HT; 10 microM) applied for up to 1 min.
      Histamine (10 microM), 5-HT (10 microM) and m-chlorophenylbiguanide (10 microM)
      were also ineffective in exciting C fibres. 4. Capsaicin, at concentrations
      ranging from 30 nM to 3 microM, evoked a sustained firing of all C fibres tested
      when applied for a period of 30 s directly onto receptive fields. Bradykinin (0.1
      1 microM) also potently excited C fibres in a concentration-related manner. The
      effect of bradykinin appeared to be mediated by a B2 receptor since it was not
      mimicked by the selective B1 receptor agonist [des-Arg9]-bradykinin (3 microM)
      and was abolished by prior application of the selective B2 receptor antagonist D
      Arg-[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (HOE 140; 0.1 microM). HOE 140 was without
      effect against capsaicin-evoked discharge of C fibres. 5. Capsaicin- and
      bradykinin-evoked discharge of C fibres was present to a similar degree in
      preparations pretreated with ibuprofen (1 microM), indicating that it was not
      dependent on, or influenced by, endogenous prostaglandin production. 6. These
      data demonstrate that single vagal afferents may be studied in vitro and provide
      the first examination of the properties of sensory fibres innervating guinea-pig
      airways. C and A delta fibres both exhibit low threshold mechanical sensitivity
      but show marked differences in terms of their chemosensitivity.

PMID- 8271199
TI  - Correlation of primate red nucleus discharge with muscle activity during free
      form arm movements.
AB  - 1. We recorded from 239 neurons located in the magnocellular division of the red
      nucleus of four alert macaque monkeys. At the same time, we recorded
      electromyographic (EMG) signals from as many as twenty electrodes chronically
      implanted on muscles of the shoulder, arm, forearm and hand. We recorded EMG
      signals for periods ranging from several months to a year. 2. The monkeys were
      trained to perform three free-form food retrieval tasks, each of which activated
      all of the recorded muscles and most of the neurons. The 'prehension' task
      required simply that the monkey grasp a piece of food from a fixed point in
      space. The 'barrier' task required the monkey to reach around a small barrier to
      obtain the food, and the 'Kluver' task required that food be removed from small
      holes. During the prehension task, we found approximately equal numbers of
      neurons that were strongly active while the hand was being moved toward the
      target (70% of units), and while the food was being grasped (60%). Relatively few
      units were active as the hand was returned to the mouth (15%). 3. Data files of 1
      2 min duration were collected while the monkey performed a single behavioural
      task. Whenever possible, we recorded files for all three tasks from each neuron.
      For each file we calculated long time-span analog cross-correlations (+/- 1.28 s)
      between instantaneous neuronal firing rate and each of the full-wave rectified,
      low-pass filtered EMG signals. We used the peak correlation and the time of the
      peak as two summary measures of the functional relation between modulation of
      neuronal activity and EMG. 4. The magnitude of the strongest correlations was
      between 0.4 and 0.5 (normalized to a perfect correlation of +/- 1.0). Distal
      muscles were the most frequently correlated, and extensors were more frequently
      correlated than flexors. For all monkeys, the lags for well correlated muscles
      were distributed broadly about a uni-modal value near 0 ms. Eighty five per cent
      of the correlations larger than or equal to 0.25 had peaks between -150 and 200
      ms. 5. The activity of each neuron was represented in a muscle co-ordinate system
      by an n-dimensional 'functional linkage vector', each element of which was the
      peak correlation with one of n muscles. The vector for any given neuron points in
      a particular direction in muscle space, depending on the similarity between the
      activity of the neuron and the activity of each muscle.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8271201
TI  - GABAB receptors modulate glycinergic inhibition and spike threshold in Xenopus
      embryo spinal neurones.
AB  - 1. The actions of GABAB receptors in the generation of the neuronal pattern
      underlying swimming in the Xenopus embryo have been investigated using the
      agonist baclofen. 2. Baclofen (10-100 microM) greatly reduced the length of
      swimming episodes and ventral root spike amplitude in a reversible manner. These
      effects were blocked by CGP 35348 (200-300 microm) and hydroxysaclofen (200-300
      microM). 3. Baclofen (10-100 microM) reduced the amplitude of glycinergic IPSPs
      in motoneurones during fictive swimming. 4. Strychnine-sensitive spontaneous
      miniature inhibitory postsynaptic potentials (mIPSPs) were recorded from
      motoneurones. While baclofen (10-100 microM) had no effect on the amplitude of
      the mIPSPs it greatly decreased their frequency of occurrence. 5. GABAB receptors
      may therefore be present on the terminals of commissural interneurones, the only
      glycinergic neurones in the Xenopus embryo's nervous system, and act to reduce
      neurotransmitter release. 6. Baclofen reduced the reliability of action potential
      firing in motoneurones during fictive swimming without an apparent effect on
      excitation. 7. Baclofen increased the threshold to action potential firing in
      response to the injection of depolarizing current in motoneurones. 8. The current
      voltage relationships of motoneurones were investigated. Baclofen (10-100 microM)
      did not change the resting membrane potential, slope conductance or the membrane
      rectification.

PMID- 8271200
TI  - Mobile and immobile calcium buffers in bovine adrenal chromaffin cells.
AB  - 1. The calcium binding capacity (kappa S) of bovine chromaffin cells preloaded
      with fura-2 was measured during nystatin-perforated-patch recordings. 2.
      Subsequently, the perforated patch was ruptured to obtain a whole-cell recording
      situation, and the time course of kappa S was monitored during periods of up to
      one hour. 3. No rapid change (within 10-20 s) of kappa S was observed upon
      transition to whole-cell recording, as would be expected, if highly mobile
      organic anions contributed significantly to calcium buffering. However,
      approximately half of the cells investigated displayed a drop in kappa S within 2
      5 min, indicative of the loss of soluble Ca2+ binding proteins in the range of 7
      20 kDa. 4. The average Ca2+ binding capacity (differential ratio of bound calcium
      over free calcium) was 9 +/- 7 (mean +/- S.E.M.) for the poorly mobile component
      and 31 +/- 10 for the fixed component. It was concluded that a contribution of 7
      from highly mobile buffer would have been detected, if present. Thus, this value
      can be considered as an upper bound to highly mobile Ca2+ buffer. 5. Both mobile
      and fixed calcium binding capacity appeared to have relatively low Ca2+ affinity,
      since kappa S did not change in the range of Ca2+ concentrations between 0.1 and
      3 microM. 6. It was found that cellular autofluorescence and contributions to
      fluorescence of non-hydrolysed or compartmentalized dye contribute a serious
      error in estimation of kappa S. 'Balanced loading', a degree of fura-2 loading
      such that the calcium binding capacity of fura-2 equals cellular calcium binding
      capacity, minimizes these errors. Also, changes in kappa S at the transition from
      perforated-patch to whole-cell recording can be most faithfully recorded for
      similar degrees of loading in both situations. 7. Nystatin was found unable to
      make pores from inside of the plasma membrane of chromaffin cells. With careful
      preparation and storage the diluted nystatin solution maintained its high
      activity of membrane perforation for more than one week. 8. An equation for the
      effective diffusion constant for total cytoplasmic calcium, D'Ca, was derived,
      which takes into account fixed buffer and poorly mobile buffer as determined, as
      well as calcium bound to fura-2 and some highly mobile buffers.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8271202
TI  - Morphine tolerance and inhibition of oxytocin secretion by kappa-opioids acting
      on the rat neurohypophysis.
AB  - 1. The present study investigated the mechanisms by which endogenous opioids
      regulate oxytocin secretion at the level of the posterior pituitary gland.
      Effects of the selective kappa-agonist U50,488 on oxytocin secretion were studied
      in urethane-anaesthetized lactating rats. Oxytocin secretion in response to
      electrical stimulation (0.5 mA, matched biphasic 1 ms pulses, 50 Hz, 60-180
      pulses) of the neurohypophysial stalk was bioassayed on-line by measuring
      increases in intramammary pressure, calibrated with exogenous oxytocin.
      Intravenous (I.V.) U50,488 inhibited electrically stimulated oxytocin secretion,
      without affecting mammary gland sensitivity to oxytocin. The inhibition was dose
      related, with an ID50 of 441 (+194, -136) micrograms/kg and was naloxone
      reversible. Antagonism of endogenous beta-adrenoceptor activation by propranolol
      (1 mg/kg) reduced the potency of U50,488. The selective mu-agonist morphine (up
      to 5 mg/kg), had no effect on electrically stimulated oxytocin secretion, but
      depressed the mammary response to oxytocin. 2. In lactating rats given
      intracerebroventricular (I.C.V.) morphine infusion for 5 days to induce tolerance
      and dependence, I.V. U50,488 still inhibited electrically stimulated oxytocin
      secretion, but the ID50 was reduced to 170 (+78, -54) micrograms/kg; thus at the
      posterior pituitary the sensitivity of kappa-receptors is enhanced rather than
      reduced in morphine-tolerant rats, indicating the absence of cross-tolerance. In
      these rats, naloxone produced a large, sustained, fluctuating increase in
      intramammary pressure indicating morphine-withdrawal excitation of oxytocin
      secretion; I.V. U50,488 diminished this response, confirmed by radioimmunoassay,
      demonstrating the independence of mu- and kappa-receptors regulating oxytocin
      secretion. 3. In pregnant rats, I.C.V. infusion of morphine from day 17-18 of
      pregnancy delayed the start of parturition by 4 h, but did not significantly
      affect the progress of parturition once established, indicating tolerance to the
      inhibitory actions of morphine on oxytocin secretion in parturition, and lack of
      cross-tolerance to endogenous opioids restraining oxytocin in parturition. 4.
      Neurointermediate lobes from control and I.C.V. morphine-infused virgin rats were
      impaled on electrodes and perifused in vitro. Vasopressin and oxytocin release
      from the glands was measured by radioimmunoassay. Each gland was exposed to two
      periods of electrical stimulation (13 Hz, for 3 min). Naloxone (5 x 10(-6) M) was
      added before the second stimulation; half the lobes from each I.C.V. treatment
      were exposed to 5 x 10(-5) M morphine throughout.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8271203
TI  - Differential sympathetic reactions during cerebral ischaemia in cats: the role of
      desynchronized nerve discharge.
AB  - 1. Sympathetic nerve discharge (SND) of three postganglionic nerves with
      different functions and anatomical locations was simultaneously recorded at rest
      and during severe cerebral ischaemia (Cushing reaction). The three nerves,
      controlling the heart (inferior cardiac nerve), visceral (renal nerve) and
      skeletal muscle circulation (vertebral nerve), were selected with the assumption
      that their activity pattern will represent the differential central autonomic
      command to the major players of the circulatory response to cerebral ischaemia.
      2. Changes in the power density spectra of the nerve signals, and in the pairwise
      coherence functions, elicited by the cerebral ischaemia, were evaluated
      separately for the rhythmic (R-SND, i.e. between 0 and 6 Hz) and high-frequency
      (HF-SND, i.e. between 12 and 100 Hz) components of the nerve signals. 3. The
      sympathetic nerve response to cerebral ischaemia developed in two phases. Phase 1
      was a massive R-SND reaction and phase 2 was characterized by SND
      desynchronization and by the emergence of HF-SND. The power of HF-SND occupied a
      wide band between 12 and 80 Hz with maximum between 20 and 30 Hz. All three
      nerves were involved in the Cushing response but the magnitude and character of
      the reactions were specific for each nerve. In the cardiac nerve, the power of
      the rhythmic component of the discharge increased almost twice the control and
      remained dominant during the whole reaction, strongly modulating HF-SND during
      the second phase. In the vasomotor nerves, R-SND was suppressed during phase 2
      and HF-SND occupied 65% of the total power of the signal. Near equal R- to HF-SND
      proportions, however, were reached on different activity levels in renal and
      vertebral nerves. Whereas total renal SND did not change, the power of the
      vertebral SND increased more than twice. In addition, desynchronization in the
      vertebral SND was preceded by a massive R-SND reaction during phase 1, which was
      missing in the renal nerve. 4. For all possible nerve pairs, R-SND was highly
      coherent before the reaction and remained so during intracranial pressure
      elevation, regardless of the direction and magnitude of the changes in absolute
      and/or relative power of this component in different nerves. On the other hand,
      HF-SND never correlated between any of the nerve pairs indicating that this
      component in each nerve originated from specific sources of regional sympathetic
      activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271204
TI  - Whole-cell recordings of inwardly rectifying K+ currents activated by 5-HT1A
      receptors on dorsal raphe neurones of the adult rat.
AB  - 1. An inwardly rectifying K+ current activated by serotonin (5-HT) was recorded
      from acutely isolated adult dorsal raphe (DR) neurones using the whole-cell
      recording mode of the patch clamp technique. 2. The 5-HT-induced K+ current (I5
      HT) was only visible at an [K+]0 > 5 mM and it was observed in 69% of the cells.
      3. The reversal potential for I5-HT was close to the potassium equilibrium
      potential and was shifted by 51 mV per 10-fold change in [K+]0 indicating that I5
      HT was carried predominantly by K+. The chord conductance of I5-HT at -90 mV was
      proportional to the external [K+] raised to a fractional power. 4. A dose
      response relationship revealed that I5-HT was activated with an ED50 of 30 nM.
      Ba2+ (0.1 mM) blocked I5-HT completely. Spiperone reversibly antagonized the
      response to 5-HT and 8-OHDPAT (8-hydroxy-2-(di-n-propylamino)tetralin) mimicked
      the response indicating that the receptor activated was of the 5-HT1A subtype. 5.
      The response to 5-HT was largely prevented by in vitro pretreatment of the cells
      with pertussis toxin (PTX) indicating the involvement of a PTX-sensitive G
      protein in the transduction mechanism. 6. cAMP and lipoxygenase metabolites, both
      implicated in the modulation of similar currents in other preparations, were
      found not to alter the effectiveness of 5-HT. 7. Glibenclamide and tolbutamide,
      blockers of the ATP-regulated K+ channel, did not reduce the effect of 5-HT in DR
      neurones. 8. These results show that in acutely isolated adult DR neurones 5-HT
      activates an inwardly rectifying K+ current and this involves a PTX-sensitive G
      protein in the transduction pathway which may interact with the K+ channel
      directly.

PMID- 8271205
TI  - Unitary properties of potassium channels activated by 5-HT in acutely isolated
      rat dorsal raphe neurones.
AB  - 1. Single inwardly rectifying K+ channel currents were recorded from acutely
      isolated adult serotonergic dorsal raphe (DR) neurones using the cell-attached
      and outside-out patch clamp configuration. 2. Four equally spaced conductance
      levels were observed in both outside-out and cell-attached patch recordings with
      conductance levels averaging 11, 21, 30 and 40 pS. Larger conductance openings
      (50-120 pS) were seen less frequently. 3. When using 136 [K+]0 the single channel
      I-V relation was linear in the range 0 mV to -100 mV in all cases. 4. Transitions
      between the various conductance levels were observed, as were apparent direct
      opening and closing to each individual conductance level. Furthermore openings of
      11, 21 and 30 pS were observed in almost all the patches. These results suggest
      that the different-sized events result from substrates of a single channel rather
      than several different channels with different conductances. 5. Unitary K+
      channel current probability of opening, recorded in cell-attached patch, was
      unchanged after 5-hydroxytryptamine (5-HT) was added to the bath outside the
      patch pipette which suggests that no easily diffusible second messenger was
      involved. 6. The single K+ channel activity, however, was increased on average by
      670% following the addition of 5-HT to the bath when recording channel activity
      in the outside-out configuration. Usually all K+ channel subconductance levels
      increased in activity but the largest increases occurred in the events with 30
      and 40 pS conductance. 7. These results suggest that 5-HT enhances the
      probability of opening of the resting K+ channel activity, which can open to
      several levels of conductance, and that no new channel or freely diffusible
      second messenger is involved in the response.

PMID- 8271206
TI  - Experimental myopia in a diurnal mammal (Sciurus carolinensis) with no
      accommodative ability.
AB  - 1. We examined the functional morphology of the intra-ocular muscles of the grey
      squirrel using pharmacological and histological methods. Using sympathomimetic
      (phenylephrine) and parasympathomimetic (carbachol) agents, administered by
      transcorneal iontophoresis, the response of the iris sphincter and dilator
      muscles and the ciliary muscle were recorded. Measurement techniques included
      both streak retinoscopy and coincidence optometry for measurement of ocular
      refraction and high resolution ultrasonography to monitor changes in the intra
      ocular component dimensions. 2. The grey squirrel was found not to possess a
      functional accommodative system. No change in ocular refraction or intra-ocular
      dimensions could be induced with 40% carbachol. Marked changes in pupil diameter
      occurred with topical application of both phenylephrine (dilation) and carbachol
      (constriction). Histological findings were in agreement with pharmacological
      findings in showing well developed iris sphincter and dilator muscles but only a
      poorly developed ciliary muscle. 3. Calculation of the depth of focus of the grey
      squirrel eye reveals that this could be sufficient to account for the behavioural
      observations of near viewing habits. 4. We then determined whether we could
      induce axial elongation of the vitreous chamber and a consequent myopia by
      monocular deprivation (MD) of pattern vision. 5. Monocular deprivation of pattern
      vision produced a significant experimental myopia due to axial elongation of the
      vitreous chamber in the deprived eye. 6. The results demonstrate that a
      functional accommodative system is not necessary to induce experimental myopia in
      the grey squirrel eye.

PMID- 8271207
TI  - Enhancement by atropine of the pancreatic exocrine secretions evoked by vagal
      stimulation in the pithed rat.
AB  - 1. Pancreatic secretions were collected in response to 15 min periods of
      bilateral stimulation of the cervical vagus nerves in the pithed rat. 2. The
      weight of juice, total HCO3- and total protein evoked by a second period of vagal
      stimulation were essentially similar to those of the first period of vagal
      stimulation. 3. When the second period of vagal stimulation was preceded by an
      intravenous bolus injection of atropine sufficient to block the vagally induced
      bradycardia, the weight of secretion and total protein were greatly potentiated
      over an extended time course far exceeding that of the period of vagal
      stimulation. Total HCO3- was unchanged. 4. By contrast, atropine was effective in
      antagonizing the stimulatory effects of the muscarinic agonist methacholine
      injected intravenously. 5. The putative VIP (vasoactive intestinal polypeptide)
      antagonist [D-p-chloro-Phe6, Leu17]-VIP injected intravenously also increased the
      vagally evoked weight of juice, with total HCO3- and total protein unchanged.
      This was explicable by a partial agonist effect which was additive to the
      stimulatory action of vagal stimulation. 6. To explain these results, it is
      proposed that endogenously released acetylcholine exerts a negative feedback
      effect on the postganglionic varicosities which release both acetylcholine and
      another cotransmitter which was not excluded as being VIP. In the presence of
      atropine, the cotransmitter is proposed to be released from the inhibitory
      feedback, thus enhancing the response to vagal stimulation.

PMID- 8271208
TI  - Skeletal muscle substrate utilization during submaximal exercise in man: effect
      of endurance training.
AB  - 1. The influence of training-induced adaptations in skeletal muscle tissue on the
      choice between carbohydrates (CHO) and lipids as well as the extra- vs.
      intracellular substrate utilization was investigated in seven healthy male
      subjects performing one-legged knee-extension exercise. In each subject one of
      the knee extensors was endurance trained for eight weeks, whereafter the trained
      (T) and non-trained (NT) thighs were investigated a week apart. 2. The activity
      of beta-hydroxy-acyl-coenzyme A dehydrogenase (HAD) and capillary density in the
      knee extensors were significantly larger in T than in NT. 3. During dynamic knee
      extension exercise, performed at the same absolute intensity for 2 h, femoral
      venous blood flow was lower in T than in NT (P < 0.05), but oxygen uptake was
      similar. 4. Respiratory quotient (RQ) values over the exercising thigh, averaging
      0.81 (T) vs. 0.91 (NT; P < 0.05) indicated that a shift towards a larger fat
      combustion occurred with endurance training. 5. Both free fatty acids (FFA) and
      serum triacylglycerol contributed to the utilization of fat in NT and T muscles
      with no significant contribution from muscle fibre triacylglycerol. 6. At high
      plasma FFA concentrations net uptake of FFA plateaued in NT but not in T muscles.
      7. The findings suggest that FFA uptake in exercising muscle is a saturable
      process and that the transport capacity is enhanced by training. The lower CHO
      utilization in the T leg was mainly a function of the glycogenolysis of the
      muscle being reduced. Hormones such as insulin, noradrenaline and adrenaline are
      unlikely to play a role in this shift as differences in plasma levels during T
      and NT leg exercise were small and insignificant, implying that local structural
      and functional adaptations of the training muscle are crucial for the observed
      shifts in the metabolic response to exercise.

PMID- 8271209
TI  - Effect of vision and stance width on human body motion when standing:
      implications for afferent control of lateral sway.
AB  - 1. Measurements of human upright body movements in three dimensions have been
      made on thirty-five male subjects attempting to stand still with various stance
      widths and with eyes closed or open. Body motion was inferred from movements of
      eight markers fixed to specific sites on the body from the shoulders to the
      ankles. Motion of these markers was recorded together with motion of the point of
      application of the resultant of the ground reaction forces (centre of pressure).
      2. The speed of the body (average from eight sites) was increased by closing the
      eyes or narrowing the stance width and there was an interaction between these two
      factors such that vision reduced body speed more effectively when the feet were
      closer together. Similar relationships were found for components of velocity both
      in the frontal and sagittal planes although stance width exerted a much greater
      influence on the lateral velocity component. 3. Fluctuations in position of the
      body were also increased by eye closure or narrowing of stance width. Again, the
      effect of stance width was more potent for lateral than for anteroposterior
      movements. In contrast to the velocity measurements, there was no interaction
      between vision and stance width. 4. There was a progressive increase in the
      amplitude of position and velocity fluctuations from markers placed higher on the
      body. The fluctuations in the position of the centre of pressure were similar in
      magnitude to those of the markers placed near the hip. The fluctuations in
      velocity of centre of pressure, however, were greater than of any site on the
      body. 5. Analysis of the amplitude of angular motion between adjacent straight
      line segments joining the markers suggests that the inverted pendulum model of
      body sway is incomplete. Motion about the ankle joint was dominant only for
      lateral movement in the frontal plane with narrow stance widths (< 8 cm). For all
      other conditions most angular motion occurred between the trunk and leg. 6. The
      large reduction in lateral body motion with increasing stance width was mainly
      due to a disproportionate reduction in the angular motion about the ankles and
      feet. A mathematical model of the skeletal structure has been constructed which
      offers some explanation for this specific reduction in joint motion.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8271210
TI  - Synapse formation and elimination during growth of the pectoral muscle in Xenopus
      laevis.
AB  - 1. Synapse formation and synapse elimination were studied in the pectoral muscle
      of Xenopus laevis. 2. Histology showed that fibres were not added during
      postmetamorphic growth. Most fibres were innervated at two widely separated
      junctions and this number did not change as frogs grew. 3. Intracellular
      recording revealed that fibres with two junctions could be mononeuronally
      innervated, or innervated in one of three different polyneuronal patterns. A
      growth-related shift in innervation pattern was observed, with the polyneuronal
      patterns replaced by mononeuronal innervation. 4. Endplate potentials (EPPs)
      evoked by low-frequency nerve stimulation were simultaneously measured at both
      junctions on individual fibres. For each fibre, the ratio of EPP amplitudes
      (smaller/larger) was calculated. When the two junctions were innervated by
      different motoneurones (A-B), the median EPP ratio was smaller than when the two
      junctions were innervated by the same motoneurone (A-A), although the difference
      was not significant. 5. The difference in the ratio of EPP amplitudes became
      significant, however, if junctions were conditioned by a train of fifty stimuli
      at 10 Hz. Immediately after such a train, EPP ratios for A-B fibres were
      significantly smaller than ratios for A-A fibres. This difference was due to
      greater synaptic depression at one of the junctions on A-B fibres. 6. We
      concluded that enhanced depression of the EPP upon repetitive stimulation is a
      physiological correlate of the competition that underlies synapse elimination.

PMID- 8271211
TI  - Effects of aerosol-applied capsaicin, histamine and prostaglandin E2 on airway
      sensory receptors of anaesthetized cats.
AB  - 1. Capsaicin, prostaglandin E2 (PGE2) and histamine are potent stimuli for reflex
      coughing and bronchoconstriction in many species including man. We have studied
      the effects of solutions of capsaicin, PGE2 and histamine on airway sensory
      receptors when administered as inhaled aerosols to the lower respiratory tract in
      anaesthetized, paralysed and artificially ventilated cats. 2. Histamine,
      administered by aerosol (6 breaths of a 1 mg ml-1 solution) and intravenously (10
      micrograms kg-1), caused an increase in the rate of discharge from rapidly
      adapting stretch receptors (RARs) and caused bronchoconstriction. 3. Six breaths
      of a capsaicin aerosol generated from solutions of 0.1 or 1 mg ml-1 stimulated
      six out of nine RARs tested. Bronchoconstriction occurred with and without RAR
      stimulation. The diluent for the capsaicin aerosol had no significant effect on
      pulmonary mechanics or rate of RAR discharge. 4. Administration of increasing
      concentrations (0.001-1 mg ml-1) of PGE2 aerosol given in six breaths (at 6 min
      intervals) caused a dose-dependent increase in the rate of discharge of eight
      RARs tested and caused bronchoconstriction. The diluent for the PGE2 aerosol had
      no effect on pulmonary mechanics or rate of RAR discharge. 5. Inhalation of
      aerosols of histamine (6 breaths of 1 mg ml-1 solution) and capsaicin (3 breaths
      of 0.1 mg ml-1 solution) stimulated all six lung C fibre endings studied (3
      pulmonary and 3 bronchial). These aerosols of capsaicin and histamine also caused
      bronchoconstriction. 6. We conclude that solutions of capsaicin and PGE2, when
      delivered by aerosol to the airway epithelial surface, are not selective
      stimulants of C fibres. Both agents can stimulate RARs. Activation of some but
      not all RARs tested, by inhaled capsaicin, suggests that there are subpopulations
      of capsaicin-sensitive and -insensitive receptors. Stimulation of airway RARs by
      a range of pharmacologically active agents released by airway inflammation may
      contribute to reflex coughing and bronchoconstriction in man.

PMID- 8271212
TI  - Interrelation between baroreceptor and macula densa mechanisms in the control of
      renin secretion.
AB  - 1. It was the aim of this study to examine the interrelation between
      'baroreceptor' function and the macula densa signal in the control of renin
      secretion from the kidneys. To this end we investigated the effects of frusemide
      and bumetanide, two different inhibitors of the macula densa Na(+)-K(+)-2Cl-
      cotransport, on pressure-dependent renin release from isolated perfused rat
      kidneys. In addition, pressure modulation of renin secretion from hydronephrotic
      kidneys devoid of macula densa structures was examined. 2. Basal flow rate
      through isolated kidneys was 13.5 +/- 1.0 ml min-1 g-1 at a renal artery pressure
      of 100 mmHg and corresponding renin secretory rates were 5.5 +/- 0.5 (ng
      angiotensin I (Ang I) h-1) min-1 g-1 (mean +/- S.E.M., n = 15). 3. Frusemide (10
      100 microM) and bumetanide (5-50 microM) increased urine flow rates and
      stimulated urinary sodium excretion in a dose-dependent fashion from 13.0 +/- 2.5
      mumol min-1 g-1 (n = 10) under control conditions to maximal values of 38.0 +/-
      5.0 (n = 5) and 37.0 +/- 2.0 mumol min-1 g-1 (n = 5), respectively. Both drugs
      also induced concentration-dependent decreases of the renal vascular resistance.
      The vasorelaxant effects of frusemide and bumetanide were paralleled by an
      increase of renin secretion to a maximum of 21 +/- 4 (ng Ang I h-1) min-1 g-1 (n
      = 10). On a molar basis bumetanide was twice as potent as frusemide in
      stimulating renin secretion. 4. Lowering of the perfusion pressure from 100 to 40
      mmHg resulted in a prompt increase of renin release yielding secretion rates of
      92 +/- 10 (ng Ang I h-1) min-1 g-1 (n = 15). In the presence of frusemide (100
      microM) and bumetanide (50 microM) renin secretion rates at 40 mmHg were 97 +/-
      11 and 133 +/- 24 (ng Ang I h-1) min-1 g-1 (n = 6), respectively. Renin release
      stimulated by bumetanide was significantly reduced to 8.0 +/- 1.5 (ng Ang I h-1)
      min-1 g-1 (n = 5) by elevating the perfusion pressure from 100 to 140 mmHg. 5.
      Lowering the renal artery pressure from 100 to 40 mmHg in isolated perfused rat
      hydronephrotic kidneys devoid of tubular structures increased renin secretion
      rates from 4.5 +/- 1.0 to 22.5 +/- 2.5 (ng Ang I h-1) min-1 (n = 5).(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8271213
TI  - Does endogenous peripheral arginine vasopressin have a role in the febrile
      responses of conscious rabbits?
AB  - 1. The actions of peripheral arginine vasopressin (AVP) on the febrile responses
      of conscious rabbits induced by peripherally administered
      polyinosinic:polycytidylic acid (poly(I).poly(C)) have been studied using an AVP
      V1 receptor antagonist ([deamino-Pen1, O-Me-Tyr2, Arg8]-vasopressin). 2.
      Temperature responses were monitored continuously using rectal thermistor probes.
      Test substances were administered intravenously (i.v.). Blood samples were taken
      at timed intervals from a marginal ear vein and plasma PGE2 and PGF2 alpha levels
      determined by radioimmunoassay. 3. Poly(I).poly(C) (2.5 micrograms/kg) stimulated
      a reproducible biphasic rise in body temperature with a lag phase of 45-60 min
      and peaks at 90 and 225 min. The febrile response was accompanied by a 5-fold
      rise in circulating immunoreactive (ir) PGE2, which peaked after 90 min and
      remained elevated up to 300 min. Poly(I).poly(C) also stimulated a 2.5-fold rise
      in circulating irPGF2 alpha, which peaked after 150 min and was followed by a
      return to basal levels after 300 min. 4. The overall magnitude of the febrile
      response to poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly
      antagonized by the AVP V1 receptor antagonist (250 micrograms/kg, i.v.)
      administered 5 min prior to the pyrogen. 5. The irPGE2 response to
      poly(I).poly(C) (2.5 micrograms/kg, i.v.) was significantly antagonized by the
      AVP V1 receptor antagonist (250 micrograms/kg, i.v.) administered 5 min prior to
      the pyrogen. The irPGF2 alpha response was only reduced at the peak 150 min time
      point measurement. 6. In conclusion, these results show a modulatory role for a
      peripherally administered AVP V1 antagonist in the febrile responses to
      poly(I).poly(C), suggesting a possible propyretic role for endogenous peripheral
      AVP. This modulatory role appears to be mediated via actions on prostaglandin E2.

PMID- 8271214
TI  - Calcium currents elicited by voltage steps and steady voltages in myocytes
      isolated from the rat basilar artery.
AB  - 1. Whole-cell patch clamp methods were used to record Ca2+ channel currents from
      isolated rat basilar arterial myocytes either in response to voltage steps or at
      steady holding potentials. Inward currents were rapidly and reversibly blocked by
      2 mM Co2+, and this solution was routinely used to subtract leakage currents. 2.
      Peak currents measured in response to voltage steps were -85 +/- 23 pA (n = 7) in
      physiological Ca2+ (1.8 mM) and -256 +/- 39 pA (n = 19) in 10 mM Ba2+. The time
      course of activation and inactivation were unaffected by changing the holding
      potential from -88 to -48 mV, and thus we found no evidence for a component of
      current flowing through transient Ca2+ channels. 3. Activation curves were
      constructed by dividing the macroscopic current by the single Ca2+ channel
      current. The product of the number of functional channels and the open-state
      probability (NPo) measured in this way rose to around 2000. Its dependence on
      voltage was fitted by a Boltzmann function with half-activation at -8.6 mV in
      physiological Ca2+ concentrations and a steepness factor in the range 6-8 mV. 4.
      In physiological solution, block by external Mg2+ reduced peak current through
      Ca2+ channels by 17%. 5. Steady-state currents were measured by holding the cell
      at a fixed voltage and rapidly applying Co2+ to block the current through Ca2+
      channels. Steady-state currents could be detected at voltages as negative as -58
      mV, and persisted for more than 15 min, suggesting that Ca2+ channels in this
      artery may provide a steady-state Ca2+ influx that contributes to resting
      contractile tone.

PMID- 8271215
TI  - Testing the common neural integrator hypothesis at the level of the individual
      abducens motoneurones in the alert cat.
AB  - 1. As far as horizontal eye movements are concerned, the well-known hypothesis of
      a common neural integrator states that the eye-position signal is generated by a
      common network, regardless of the type of versional movement. The aim of this
      study was to evaluate the validity of this hypothesis by analysing the behaviour
      of the abducens motoneurones, the system into which the horizontal neural
      integrator(s) project(s). If there were a common neural integrator, the different
      motoneurones would receive the eye position signal through the same pathway and
      the sensitivity to eye position would be the same regardless of the type of
      versional movement. If there were multiple integrators, the sensitivity to eye
      position in one type of versional movement might be different from the
      sensitivity to eye position in another type of versional movement, at least for
      occasional motoneurones. 2. The discharge of thirty-one antidromically identified
      abducens motoneurones was recorded in the alert cat during spontaneous eye
      movements made in the light and in response to sinusoidal rotations of the head
      in complete darkness. 3. All of the abducens motoneurones exhibited a burst of
      action potentials for lateral saccades. During fixation between saccades, they
      maintained a steady firing rate that increased as the cat fixated increasingly
      lateral eye positions. 4. For each abducens motoneurone, the sensitivity to eye
      position (Kf) was determined from measurements carried out during intersaccadic
      fixations. Kf was calculated from the slope of the firing rate-eye position
      linear regression line. 5. The discharge rate of the identified motoneurones was
      observed during four sinusoidal vestibular stimulations (+/- 10 deg, 0.10 Hz; +/-
      20 deg, 0.10 Hz; +/- 30 deg, 0.10 Hz; +/- 40 deg, 0.10 Hz). The motoneurones
      exhibited a burst of activity during fast phases in the lateral direction and
      paused during fast phases in the opposite direction. During slow phases,
      motoneurones modulated their activity as a function of the vestibularly induced
      eye movements except for slow phases that occurred in position ranges below their
      recruitment threshold. In these cases their activity was cut off. 6. A new method
      was developed to measure the sensitivity to eye position of neurones during
      vestibular slow phases. The difficulty came from the fact that, during slow
      phases, eye velocity and eye position changed simultaneously and that each of
      those two variables could influence neuronal activity.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8271216
TI  - Endothelin and endothelium-derived relaxing factor control of basal renovascular
      tone in hydronephrotic rat kidneys.
AB  - 1. In order to investigate the control of renal vascular tone by endothelin (ET)
      and endothelium-derived relaxing factor (EDRF) under basal conditions, we infused
      intravenously anti-ET-1/3 antibodies (a-ET-1/3) and NG-nitro-L-arginine methyl
      ester (L-NAME) in split hydronephrotic rat kidneys. 2. A 25 min I.V. infusion of
      a-ET-1/3 (4.0 x 10(-13) mol kg-1 min-1) induced a time-dependent vasodilatation
      of arcuate (16.5%) and interlobular arteries (18.6%) as well as an increase of
      glomerular blood flow (GBF) by 32%. 3. Inhibition of EDRF synthesis by L-NAME
      produced a marked vasoconstriction of arcuate arteries (17.1%) and efferent
      (20.1%) arterioles and a decrease of GBF by 43%. 4. Co-infusion of a-ET-1/3 and L
      NAME induced efferent vasoconstriction by 19.5%, whereas preglomerular vessel
      diameters remained unchanged. 5. The specificity of a-ET-1/3 effects was
      confirmed by simultaneous I.V. application of a-ET-1/3 and ET-1 (160 ng I.V.)
      which produced no significant vascular effects. Injection of ET-1 alone
      constricted arcuate arteries and decreased glomerular blood flow by 25%. 6.
      Experiments in normal rat kidneys with a-ET-1/3 I.V. revealed an increase of
      renal blood flow by 21%. 7. Our results demonstrate a physiological control of
      basal vascular tone in larger preglomerular arterioles by ET and EDRF. Efferent
      arteriolar tone is predominantly controlled by EDRF.

PMID- 8271217
TI  - Regulation of unloaded cell shortening by sarcolemmal sodium-calcium exchange in
      isolated rat ventricular myocytes.
AB  - 1. Regulation of unloaded cell shortening and relaxation by sarcolemmal Na(+)
      Ca2+ exchange was investigated in rat ventricular myocytes. Contraction of single
      cells at 22 +/- 1 degrees C was measured simultaneously with membrane current and
      voltage using the whole-cell voltage clamp technique in combination with a video
      edge-detection device. 2. The extent of mechanical activation (cell shortening
      amplitude) was strongly dependent on diastolic membrane potential over the
      voltage range -140 to -50 mV. This voltage sensitivity of contraction was
      abolished completely when a recently described inhibitory peptide of the cardiac
      Na(+)-Ca2+ exchanger (XIP, 2 x 10(-5) M) was present in the recording pipette,
      demonstrating that in rat ventricular cells Na(+)-Ca2+ exchange is modulated by
      diastolic membrane potential. 3. Possible influences of Na(+)-Ca2+ exchange on
      contraction were studied from a holding potential of -80 mV. Depolarizations (-50
      to +60 mV) resulted in a bell-shaped shortening-voltage (S-V) relationship. These
      contractions were suppressed completely by either Cd2+ (10(-4) M) or verapamil
      (10(-5) M), but remained unchanged during superfusion with tetrodotoxin (TTX, 1.5
      x 10(-5) M), when [NA+]o was reduced from 140 to 10 mM by substitution with
      either Li+ or Cs+ ions or when pipette Na+ was varied between 8 and 13 mM. XIP (2
      x 10(-5) M) increased the magnitude and duration of twitch contractions, but had
      no effect on the shape of the S-V relationship. Thus, the Ca2+ current but not
      the Na+ current or Ca2+ influx due to reversed Na(+)-Ca2+ exchange can release
      Ca2+ from the sarcoplasmic reticulum (SR) under these experimental conditions. 4.
      The effect of the rate of repolarization on cell shortening was studied under
      voltage clamp by applying ramp waveforms immediately following the
      depolarizations which activated contraction. Although slowing of the rate of
      repolarization had no effect on the first contraction following a train of
      conditioning depolarizations, a positive inotropic effect developed thereafter.
      5. Caffeine (10 mM) was applied to determine whether Na(+)-Ca2+ exchange and/or
      Ca2+ sequestration/buffering by the sarcoplasmic reticulum were primarily
      responsible for these inotropic effects. In the presence of caffeine the positive
      inotropic effect developed fully during the first test depolarization. Changes in
      the rate of repolarization had much less effect on shortening in cells dialysed
      intracellularly with XIP (2 x 10(-5) M). In combination, these results suggest
      that the changes in the inotropic effects resulting from changes in rate of
      repolarization may be due to altered loading and release of Ca2+ from the
      SR.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271218
TI  - Effect of sympathetic nervous system activation on the tonic vibration reflex in
      rabbit jaw closing muscles.
AB  - 1. In precollicular decerebrate rabbits we investigated the effect of sympathetic
      stimulation, at frequencies within the physiological range, on the tonic
      vibration reflex (TVR) elicited in jaw closing muscles by small amplitude
      vibrations applied to the mandible (15-50 microns, 150-180 Hz). The EMG activity
      was recorded bilaterally from masseter muscle and the force developed by the
      reflex was measured through an isometric transducer connected with the mandibular
      symphysis. 2. Unilateral stimulation of the peripheral stump of the cervical
      sympathetic by the TVR, and a marked decrease or disappearance of the ipsilateral
      EMG activity. No significant changes were detected in the EMG contralateral to
      the stimulated nerve. Bilateral CSN stimulation reduced by 60-90% the force
      reflexly produced by the jaw closing muscles and strongly decreased or suppressed
      EMG activity on both sides. This effect was often preceded by a transient TVR
      enhancement, very variable in amplitude and duration, which was concomitant with
      the modest increase in pulmonary ventilation induced by the sympathetic
      stimulation. 3. During bilateral CSN stimulation, an increase in the vibration
      amplitude by a factor of 1.5-2.5 was sufficient to restore the TVR reduced by
      sympathetic stimulation. 4. The depressant action exerted by sympathetic
      activation on the TVR is mediated by alpha-adrenergic receptors, since it was
      almost completely abolished by the I.V. administration of either phentolamine or
      prazosin, this last drug being a selective antagonist of alpha 1-adrenoceptors.
      The sympathetically induced decrease in the TVR was not mimicked by manoeuvres
      producing a large and sudden reduction or abolition of the blood flow to jaw
      muscles, such as unilateral or bilateral occlusion of the common carotid artery.
      5. The effect of sympathetic stimulation was not significantly modified after
      denervation of the inferior dental arch and/or anaesthesia of the
      temporomandibular joint, i.e. after having reduced the afferent input from those
      receptors, potentially affected by CSN stimulation, which can elicit either a jaw
      opening reflex or a decrease in the activity of the jaw elevator muscle
      motoneurons. 6. These data suggest that, when the sympathetic nervous system is
      activated under physiological conditions, there is a marked depression of the
      stretch reflex which is independent of vasomotor changes and is probably due to a
      decrease in sensitivity of muscle spindle afferents.

PMID- 8271219
TI  - GLUT 4 and insulin receptor binding and kinase activity in trained human muscle.
AB  - 1. Physical training enhances sensitivity and responsiveness of insulin-mediated
      glucose uptake in human muscle. This study examines if this effect of physical
      training is due to increased insulin receptor function or increased total
      concentration of insulin-recruitable glucose transporter protein (GLUT 4). 2.
      Seven healthy young subjects carried out single leg bicycle training for 10 weeks
      at 70% of one leg maximal oxygen uptake (VO2,max). Subsequently biopsies were
      taken from the vastus lateralis muscle of both legs. 3. Single leg VO2,max
      increased for the trained leg (46 +/- 3 to 52 +/- 2 ml min-1 kg-1 (means +/-
      S.E.M., P < 0.05), and cytochrome c oxidase activity was higher in this compared
      to the untrained leg (2.0 +/- 0.1 vs. 1.4 +/- 0.1 nmol s-1 (mg muscle)-1, P <
      0.05). Insulin binding as well as basal- and insulin-stimulated receptor kinase
      activity did not differ between trained and untrained muscle. The concentration
      of GLUT 4 protein was higher in the former (14.9 +/- 1.9 vs. 11.6 +/- 1.0
      arbitrary units (micrograms protein)-1 in crude membranes, P < 0.05). The
      training-induced increase in GLUT 4 (26 +/- 11%) matched a previously reported
      increase in maximum insulin-stimulated leg glucose uptake (25 +/- 7%) in the same
      subjects, and individual values of the two variables correlated (correlation
      coefficient (r) = 0.84, P < 0.05). 4. In conclusion, in human muscle training
      induces a local contraction-dependent increase in GLUT 4 protein, which enhances
      the effect of insulin on glucose uptake. On the other hand, insulin receptor
      function in muscle is unlikely to be affected by training.

PMID- 8271220
TI  - Control of resting membrane potential by delayed rectifier potassium currents in
      ferret airway smooth muscle cells.
AB  - 1. In order to determine the physiological role of specific potassium currents in
      airway smooth muscle, potassium currents were measured in freshly dissociated
      ferret trachealis cells using the nystatin-permeabilized, whole-cell method, at
      35 degrees C. 2. The magnitude of the outward currents was markedly increased as
      bath temperature was increased from 22 to 35 degrees C. This increase was
      primarily due to the increase in maximum potassium conductance (gK,max), although
      there was also a small leftward shift in the relationship between gK and voltage
      at higher temperatures. The maximum conductance and the kinetics of current
      activation and inactivation were also temperature dependent. At 35 degrees C,
      gating of the current was steeply voltage dependent between -40 and 0 mV. Current
      activation was well fitted by fourth-order kinetics; the mean time constants of
      activation (30 mV clamp step) were 1.09 +/- 0.17 and 1.96 +/- 0.27 ms at 35 and
      22 degrees C, respectively. 3. Outward currents using the nystatin method were
      qualitatively similar to delayed rectifier currents recorded in dialysed cells
      with high calcium buffering capacity solutions. 4-Aminopyridine (4-AP; 2 mM), a
      specific blocker of delayed rectifier potassium channels in this tissue,
      inhibited over 80% of the outward current evoked by voltage-clamp steps to
      between -10 and +20 mV (n = 6). Less than 5% of the outward current was blocked
      over the same voltage range by charybdotoxin (100 nM; n = 15), a specific
      antagonist of large-conductance, calcium-activated potassium channels in this
      tissue. 4. The degree to which delayed rectifier and calcium-activated potassium
      conductances control resting membrane potential was examined in current-clamp
      experiments. The resting membrane potential of current clamped cells was -33.6 +/
      1.0 mV (n = 62). Application of 4-AP (2 mM) resulted in a 14.4 +/- 1.0 mV
      depolarization (n = 8) and an increase in input resistance. Charybdotoxin (100
      nM) had no effect on resting membrane potential (n = 6). 5. Force measurements
      were made in isolated strips of trachealis muscle to determine the effect of
      pharmacological blockade of individual potassium conductances on resting tone. In
      the presence of tetrodotoxin (1 microM) and atropine (1 microM), 4-AP increased
      baseline tension in a dose-dependent manner, with an EC50 of 1.8 mM (n = 13);
      application of 5 mM 4-AP increased tone to 86.8 +/- 8.1% of that produced by 1
      microM methacholine, and this tone was almost completely inhibited by nifedipine
      (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271221
TI  - Block of current through T-type calcium channels by trivalent metal cations and
      nickel in neural rat and human cells.
AB  - 1. The effects of the trivalent cations yttrium (Y3+), lanthanum (La3+), cerium
      (Ce3+), neodymium (Nd3+), gadolinium (Gd3+), holmium (Ho3+), erbium (Er3+),
      ytterbium (Yb3+) and the divalent cation nickel (Ni2+) on the T-type voltage
      gated calcium channel (VGCC) were characterized by the whole-cell patch clamp
      technique using rat and human thyroid C cell lines. 2. All the metal cations
      (M3+) studied, blocked current through T-type VGCC (IT) in a concentration
      dependent manner. Smaller trivalents were the best T-channel antagonists and
      potency varied inversely with ionic radii for the larger M3+ ions. Estimation of
      half-maximal blocking concentrations (IC50s) for IT carried by 10 mM Ca2+
      resulted in the following potency sequence: Ho3+ (IC50 = 0.107 microM)
      approximately Y3+ (0.117) approximately Yb3+ (0.124) > or = Er3+ (0.153) > Gd3+
      (0.267) > Nd3+ (0.429) > Ce3+ (0.728) > La3+ (1.015) >> Ni2+ (5.65). 3. Tail
      current measurements and conditioning protocols were used to study the influence
      of membrane voltage on the potency of these antagonists. Block of IT by Ni2+,
      Y3+, La3+ and the lanthanides was voltage independent in the range from -200 to
      +80 mV. In addition, the antagonists did not affect macroscopic inactivation and
      deactivation of T-type VGCC. 4. Increasing the extracellular Ca2+ concentration
      reduced the potency of IT block by Ho3+, indicative of competitive antagonism
      between this blocker and the permeant ion for a binding site. 5. The results
      suggest that the mechanism of metal cation block of T-type VGCC is occlusion of
      the channel pore by the antagonist binding to a Ca2+/M3+ binding site, located
      out of the membrane electric field. 6. Block of T-type VGCC by Y3+, lanthanides
      and La3+ differ from the inhibition of high voltage-activated VGCC block in
      several respects: smaller cations are more potent IT antagonists; block is
      voltage independent and the antagonists do not permeate T-type channels. These
      differences suggest corresponding structural dissimilarities in the permeation
      pathways of low and high voltage-activated Ca2+ channels.

PMID- 8271222
TI  - Ca2+ oscillations and Ca2+ influx in Xenopus oocytes expressing a novel 5
      hydroxytryptamine receptor.
AB  - 1. We expressed a novel 5-hydroxytryptamine receptor (SRL) in Xenopus oocytes and
      monitored cytosolic Ca2+ through the endogenous Ca(2+)-dependent Cl- channel
      activity using the double electrode voltage-clamp technique. 2. 5
      Hydroxytryptamine (5-HT; 200 nM) led to an initial rapid oscillatory current
      followed by a pronounced secondary one, which lasted long after 5-HT wash-out (20
      40 min) and was not affected by the receptor antagonist yohimbine. 3. Both phases
      of the current were abolished by heparin demonstrating a key role for IP3-induced
      Ca2+ release. 4. Caffeine (10 mM) alone did not evoke a current but reduced both
      phases of the current evoked by 5-HT. Ryanodine had no effect. No evidence for
      Ca(2+)-induced Ca2+ release was found. 5. The secondary current activated by 5-HT
      was sensitive to changes in extracellular Ca2+, suggesting it was evoked by Ca2+
      influx. Reducing external Na+ did not affect this current, demonstrating that it
      was rather specific for Ca2+. 6. The Ca2+ influx pathway was much more sensitive
      to Cd2+ than other divalent ions (Co2+, Mn2+, Sr2+, Ba2+). It was insensitive to
      verapamil. 7. Injection of D-myo-inositol 1,4,5-trisphosphate, 3-deoxy-3-fluoro
      (IP3-F; an analogue not metabolized to D-myo-inositol 1,3,4,5-tetrakisphosphate
      (IP4)), evoked either an oscillatory current or a rapid current followed by a
      sustained secondary one. The latter was sensitive to external Ca2+ and was
      blocked by Cd2+. Heparin dramatically reduced the IP3-F-evoked current. 8.
      Perfusion in Ca(2+)-free solution, once a secondary current had been generated,
      significantly decreased the amount of intracellular Ca2+ mobilized by 5-HT,
      indicating that the Ca2+ influx pathway plays an important role in pool
      refilling. 9. Block of Ca2+ influx by Cd2+ in cells that were oscillating
      transiently increased the amplitude and then either abolished the oscillations or
      made them irregular. This effect was also elicited by increasing external Ca2+.
      10. These results demonstrate that 5-HT, acting via IP3, both releases Ca2+ from
      internal stores and evokes a pronounced Ca2+ influx. This last step is activated
      by pool depletion and is important for both refilling of the agonist-sensitive
      stores and modifying the oscillatory pattern.

PMID- 8271223
TI  - Organization of motor output in slow finger movements in man.
AB  - 1. Slow finger movements were analysed in normal human subjects with regard to
      kinematics and EMG activity of the long finger muscles. Surface EMG from the
      finger extensor and flexor muscles on the forearm was recorded along with angular
      position and angular velocity during voluntary ramp movements at single
      metacarpophalangeal joints. Angular acceleration was computed from the velocity
      record. 2. It was found that movements were not smooth but characterized by steps
      or discontinuities, often recurring at intervals of 100-125 ms, yielding velocity
      and acceleration profiles dominated by 8-10 Hz cycles. The discontinuities were
      manifest from the very first trial and thus not dependent on training. Their
      amplitude and amount varied between subjects but were relatively stable for the
      individual subject. 3. The 8-10 Hz cycles were seen with voluntary ramp movements
      of widely varying velocities, higher velocities being associated with larger
      steps recurring with the same repetition rate as the small steps of slow
      voluntary ramps. Maximal step amplitude observed was more than one order of
      magnitude larger than physiological tremor. 4. The individual 8-10 Hz cycle was
      asymmetrical in that decelerations usually reached higher peaks than the
      preceding acceleration, suggesting that the antagonist contributed with a braking
      action. Moreover, in very slow voluntary ramps, the movement cycles were often
      interspaced by periods of zero velocity, providing a highly non-sinusoidal
      velocity profile. 5. The EMG of the agonist and the antagonist muscles was
      modulated in close relation to the accelerations and decelerations respectively
      of the individual movement cycle. These modulations were present in both extensor
      and flexor muscles, although they were more consistent and usually more prominent
      in the former. 6. The findings indicate that a feature of slow finger movements
      was an 8-10 Hz periodic output to the muscular system, suggesting that slow
      finger movements are implemented by a series of biphasic force pulses, involving
      not only the shortening agonist muscle propelling the movement, but the
      antagonist muscle as well whose activity increased shortly after the agonist and
      contributed to a sharp deceleration of the individual step of movement. 7. It is
      proposed, as a hypothesis, that this biphasic motor output may reflect a similar
      organization of the descending motor command for slow finger movements. Hence,
      this command would include a series of biphasic pulses, concatenated at a rate of
      8-10 per second and a pulse-height regulator capable of setting the size of the
      pulse and thus the overall speed of the movement.

PMID- 8271224
TI  - Characterization of Ca2+ signals induced in hippocampal CA1 neurones by the
      synaptic activation of NMDA receptors.
AB  - 1. A combination of confocal microscopy, whole-cell patch-clamp recording,
      intracellular dialysis and pharmacological techniques have been employed to study
      Ca2+ signalling in CA1 pyramidal neurones, within rat hippocampal slices. 2. In
      the soma of CA1 neurones, depolarizing steps applied through the patch-pipette
      resulted in transient increases in the fluorescence emitted by the Ca2+ indicator
      fluo-3. The intensity of the fluorescence transients was proportional to the
      magnitude of the Ca2+ currents recorded through the pipette. Both the somatic
      fluorescence transients and the voltage-activated Ca2+ currents ran down in
      parallel over a period of between approximately 15-45 min. The fluorescence
      transients were considered, therefore, to be caused by increases in cytosolic
      free Ca2+. 3. Under current-clamp conditions, high-frequency (tetanic)
      stimulation (100 Hz, 1 s) of the Schaffer collateral-commissural pathway led to
      compound excitatory postsynaptic potentials (EPSPs) and somatic Ca2+ transients.
      The somatic Ca2+ transients were sensitive to the N-methyl-D-aspartate (NMDA)
      receptor antagonist D-2-amino-5-phosphonopentanoate (AP5; 100 microM). These
      transients, but not the EPSPs, disappeared with a time course similar to that of
      the run-down of voltage-gated Ca2+ currents. Tetanus-induced somatic Ca2+
      transients could not be elicited under voltage-clamp conditions. 4. Fluorescence
      images were obtained from the dendrites of CA1 pyramidal neurones starting at
      least 30 min after obtaining whole-cell access to the neurone. Measurements were
      obtained only after voltage-gated Ca2+ channel activity had run down completely.
      5. Tetanic stimulation of the Schaffer collateral-commissural pathway resulted in
      compound EPSPs and excitatory postsynaptic currents (EPSCs), under current- and
      voltage-clamp, respectively. In both cases, these were invariably associated with
      dendritic Ca2+ transients. In cells voltage-clamped at -35 mV, the fluorescent
      signal increased on average 2-fold during the tetanus and decayed to baseline
      values with a half-time (t1/2) of approximately 5 s. 6. The alpha-amino-3-hydroxy
      5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX; 10 microM) partially reduced the tetanus
      induced EPSC without affecting the Ca2+ transients. In contrast, AP5, which also
      depressed the EPSC, substantially reduced or eliminated the Ca2+ transients. 7.
      In normal (i.e. 1 mM Mg(2+)-containing) medium, NMDA receptor-mediated synaptic
      currents displayed the typical region of negative slope conductance in the peak I
      V relationship (between -90 and -35 mV). The dendritic tetanus-induced Ca2+
      transients also displayed a similar anomalous voltage dependence, decreasing in
      size from -35 to -90 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271225
TI  - Baroreceptor reflex-linked changes in catechol metabolism in the rat rostral
      ventrolateral medulla.
AB  - 1. Using in vivo voltammetry, this study relates catecholamine metabolism within
      the rat rostral ventrolateral medulla to the level of mean arterial pressure
      (MAP) under halothane anaesthesia. 2. A vasopressor region was circumscribed with
      electrical stimulations in an area located 1000-1700 microns rostral to the obex.
      A catechol signal was then ascertained within this area. The recording site was
      surrounded with phenyl-N-methyl-ethanolamine transferase immuno-positive cell
      bodies. 3. Three levels of decrease of arterial pressure were induced with
      nitroprusside infusion: -15, -35 and -55 mmHg (n = 5 in each group) from baseline
      for 30 min. This led to increases in the catechol signal which were inversely
      related to the degree of hypotension (P < 10(-4) vs. saline for the 35 and 55
      mmHg groups, P < 0.05 for the 35 mmHg group as compared to the 15 and 55 mmHg
      groups following recovery from hypotension). 4. Following sino-aortic
      deafferentation, nitroprusside-induced hypotension (-35 mmHg) did not lead to any
      change in the catechol signal in the rostral ventrolateral medulla (n = 5).
      Furthermore, controlled hypotension induced in intact rats did not evoke any
      change in the catechol signal recorded in a dopaminergic area of the midbrain,
      the ventral tegmental area (A10 area; n = 5). 5. An infusion of phenylephrine
      increased MAP by 35 mmHg from a baseline pressure of 105 mmHg for 30 min and
      evoked a non-significant decrease in the catechol signal (n = 5). In another
      group of rats a lower baseline pressure (80 mmHg) was stabilized (n = 5) with a
      higher concentration of halothane. An identical increment in pressure was then
      produced by a phenylephrine infusion and led to a significant reduction in the
      catechol signal (P < 0.05 vs. saline under similar conditions; n = 5). 6. The new
      findings of this study are that the level of activity of the metabolism of
      catecholamine in the rostral ventrolateral medulla (i) is continuously related to
      the level of arterial pressure, (ii) functions close to its resting level under
      baseline conditions and is primarily engaged during hypotension and (iii) is
      baroreflex linked. 7. Given the lack of direct evidence for a link between unit
      activity and catechol metabolism, these changes in catechol activity, recorded
      continuously in vivo next to adrenergic cell bodies, may represent the
      biochemical-specific counterpart of changes in the level of electrical unitary
      activity of presumed adrenergic cardiovascular medullospinal sympathoexcitatory
      neurons. Therefore, it provides evidence that adrenaline-synthesizing neurons in
      the rostral ventrolateral medulla respond to baroreceptor inputs.

PMID- 8271227
TI  - Addiction as a social construction: a postempirical view.
AB  - I examined the role of society and psychology as its agent in the growing problem
      of addiction in America. The social institutions of a given society establish and
      maintain a character structure unique to a particular era. The quality of that
      character is reflected in its inhabitants' individual psychological natures as
      either health or pathology. I examined the philosophical roots of psychology, its
      theories and their effect on perpetuating current erroneous beliefs about
      addiction, and psychology's role in finding real solutions.

PMID- 8271226
TI  - Mechanisms of endothelin-1-induced pulmonary vasodilatation in neonatal pigs.
AB  - 1. We determined the contributions of three independent vasodilator mechanisms
      (cyclo-oxygenase metabolites, nitric oxide and ATP-sensitive potassium channels)
      in the mediation of pulmonary vasomotor effects of endothelin-1 (ET-1) in
      neonatal pigs. 2. Lungs of piglets (2.7 +/- 0.3 days old) were perfused at
      constant flow (60 ml min-1) with recirculating Ringer-albumin solution. We
      measured pulmonary artery pressure (Ppa) and the distribution of pulmonary
      vascular resistance using the double-occlusion method. 3. ET-1 (10(-12)-10(-9) M)
      produced concentration-dependent pulmonary vasodilatation. ET-1 (10(-9) M)
      decreased Ppa from 24.5 +/- 3.1 to 17.0 +/- 3.0 cmH2O with a nadir occurring at 1
      min, followed by a slow return to baseline over 60 min (time for half-recovery
      (t1/2R) of 17.2 min). The decrease in Ppa was the result of pulmonary
      precapillary vasodilatation. Endothelin-3 (ET-3) (10(-12) and 10(-11) M) also
      induced vasodilatation comparable to equimolar concentrations of ET-1, whereas
      the selective ETB receptor agonist IRL 1620 at equimolar concentrations caused a
      more protracted vasodilatation response. 4. Neither the cyclo-oxygenase inhibitor
      indomethacin (10(-5) M) nor the KATP+ (ATP-sensitive) potassium channel blocker
      glibenclamide (10(-5) M) significantly altered the baseline Ppa; moreover,
      neither inhibitor affected the ET-1-induced vasodilatation, indicating the lack
      of involvement of cyclo-oxygenase metabolites and KATP+ channel activity in the
      mediation of the pulmonary vasodilator response to ET-1. 5. Addition of 10(-5) M
      reduced haemoglobin, which antagonizes the action of nitric oxide (NO), increased
      Ppa over prehaemoglobin levels. Haemoglobin significantly decreased the duration
      (t1/2R, 3.8 +/- 0.7 min) of pulmonary vasodilatation to ET-1, but did not abolish
      the initial phase of the response. L-N-Monomethylarginine, an inhibitor of NO
      synthesis, either alone or in combination with haemoglobin, similarly reduced the
      duration of ET-1-induced pulmonary vasodilatation. 6. The ETA receptor antagonist
      [Dpr1-Asp15]-ET-1 (Dpr, diaminoproprionic acid) had no effect on pulmonary
      vasodilatation induced by ET-1, ET-3 or IRL 1620 (suc-(Glu9,Ala11,15)-ET-1(8
      21)). This finding combined with the observed relative potencies of the peptides
      (IRL 1620 > ET-1 = ET-3) suggests that pulmonary vasodilatation was mediated by
      activation of the non-selective ETB receptor. 7. The results indicate that the
      sustained ET-1-induced pulmonary vasodilatation in neonates is probably mediated
      via ETB receptor activation and that it is critically dependent on NO.

PMID- 8271228
TI  - Attitudes toward women and rape among male adolescents convicted of sexual versus
      nonsexual crimes.
AB  - Adolescence is an important period in the development of adult sexual offending
      against women, yet it has received little attention in research on attitudes
      toward women and rape. The present study used the Attitudes Toward Women Scale
      (AWS) and Burt's (1980) Rape Myth Acceptance Scale (BRMAS) to compare the
      attitudes of 31 male adolescents convicted of sexual assaults on women (rape,
      attempted rape, indecent assault) with the attitudes of 27 male adolescents
      convicted of nonsexual violent crimes. The results showed no significant
      difference between the two groups on either measure. Furthermore, a more
      traditional, conservative attitude toward women, as measured on the AWS, did not
      significantly correlate with the endorsement of rape myths as measured on the
      BRMAS. The findings are discussed with reference to the validity and reliability
      of these measures when used with adolescents.

PMID- 8271229
TI  - Gender difference in mate preference among law students: divergence and
      convergence of criteria.
AB  - We examined six hypotheses derived from evolutionary theory regarding sex
      differences in mate-selection criteria. The subjects were 160 law students who
      viewed color photographs of live models that were paired with different status
      cues such as costume variation and descriptions of income and occupation. A
      multivariate analysis of variance and regression analyses revealed highly
      significant sex differences in the following responses: reported willingness to
      engage in unqualified sexual relations; reported willingness to have sexual
      relations with stimulus persons as compared with the willingness to engage in
      higher investment relationships such as dating and marriage; the effects of
      stimulus persons' status and physical attractiveness in determining thresholds of
      initial acceptability; and tradeoffs, that is the ability of high physical
      attractiveness to compensate for low status, and of high status to compensate for
      low physical attractiveness. Law students also responded to nine statements
      concerning prospective spouses' relative income, occupational prestige, and
      physical attractiveness. These responses exhibited sex differences consistent
      with those found in the experimental manipulation.

PMID- 8271230
TI  - Stress and burnout among teachers in Italy and France.
AB  - The aim of the present study was to show differences between culture-bound stress
      levels in two samples of elementary and junior high school teachers in Italy (N =
      299) and in France (N = 217), using the Maslach Burnout Inventory (MBI; Maslach &
      Jackson, 1981) as a questionnaire. The results confirmed the influence of
      sociocultural background on stress levels in both samples in relation to age.
      Personal accomplishment was the most discriminating indicator in the two groups.

PMID- 8271231
TI  - Being in control: a note on differences between caregiving and noncaregiving
      spouses.
AB  - Twenty-seven spouse caregivers of dementia patients and 33 noncaregiving
      (healthy) spouses, aged 54 to 90, described a stressful situation with their
      spouses and completed measures of perceived control and subjective well-being.
      Both groups were similar in their perceived lack of control over the spouse's
      behavior but differed in how control influenced positive affect. Perceived
      control over the spouse was negatively related to positive affect for the healthy
      couples but for caregivers it was positively related.

PMID- 8271232
TI  - Perceptions of excessive alcohol consumption in stressful and nonstressful
      situations among undergraduates.
AB  - We devised and administered the Alcohol Perceptions Questionnaire (APQ) to 56
      male and 51 female undergraduates in a small midwestern university. Findings
      yielded statistically significant results between the level of alcohol
      consumption reported by the subjects and their perceptions of excessive drinking
      in interpersonal situations, social group situations, and under conditions of
      subjective stress. The greater the amount of personal alcohol consumption among
      the sample, the less likely they viewed excessive drinking as a problem. In
      addition, subjects from lower income environments viewed excessive drinking in
      general as a problem, whereas subjects from higher income environments viewed
      excessive drinking as no problem at all.

PMID- 8271233
TI  - The relationship between childhood onset obesity and psychopathology in
      adulthood.
AB  - We administered the Symptom Checklist (Derogatis, 1975; SCL-90-R) to 37 obese
      subjects in outpatient treatment for obesity. Patients with early onset obesity
      demonstrated a greater frequency and higher levels of emotional distress and
      psychiatric symptomatology than patients with late onset obesity. Individuals who
      developed obesity in childhood showed more psychopathology than those who
      developed obesity later in life. Overall, these findings support the belief that
      obesity is characteristically associated with greater internal psychological
      conflict. These findings further suggest that childhood obesity could serve as a
      predictor variable for possible future psychological disturbance in obese
      populations.

PMID- 8271234
TI  - Male-female response profile differences on the WAIS-R in clients suffering from
      borderline personality disorders.
AB  - One hundred nineteen clients diagnosed with borderline personality disorders
      participated in a correlational study using standard intelligence and achievement
      measures. We expected to confirm the presence of an organic subtype that might
      help clinicians who work with this group of clients (average IQ = 79.3). We found
      gender differences that tended to support previous research on male-female
      differences. In general, the data supported the presence of an organic subtype.
      Analyses of arrest history and additional differential diagnoses showed this
      category of client relatively free of dependency concerns but manifesting signs
      of an anxiety disorder.

PMID- 8271235
TI  - Real-world knowledge facilitates interpretation of paintings by naive art
      observers.

PMID- 8271236
TI  - Phenotypic characteristics of lymphocyte populations isolated from middle
      gestation human placenta.
AB  - In order to characterize the phenotypic composition of populations of lymphoid
      cells in maternal and fetal tissues during the period of middle gestation,
      mononuclear cells were isolated from maternal peripheral blood, fetal spleen,
      fetal thymus and placenta of 18-24 week pregnancies. Peripheral blood and
      placental isolates were stained for a number of lymphoid cell markers by indirect
      immunofluorescence and analyzed by flow cytometry. Studies were performed on both
      freshly isolated mononuclear cell preparations and in vitro cultured cells after
      selective expansion in interleukin 2 (IL2). Fresh placental mononuclear cell
      isolates were an average 20% CD3+; their CD4/CD8 ratios varied among individuals.
      An average of 68% of the lymphocytes isolated from maternal peripheral blood were
      CD3+. Placental and maternal peripheral blood isolates had comparable percentages
      of CD16+ and CD20+ cells, while CD56+ cells were present at significantly greater
      numbers in the lymphocyte compartment of placenta (17%) than in peripheral blood
      (3%; P < 0.01). Lymphocyte isolates were expanded by culture with IL2 and PHA and
      stained to determine if propagated lymphocyte populations are representative of
      initial isolates. Expansion of all lymphocyte isolates favored CD3 phenotypes and
      CD8 phenotypes. Compared to expanded placenta-derived populations, expanded
      peripheral blood lymphocytes were similar with regard to percentages of all
      phenotypes except gamma/delta T cells which represented more of placental
      lymphocytes (10%) than peripheral lymphocytes (5%; P < 0.01). Surface HLA typing
      determined propagated placenta-derived lymphocytes to be of maternal and not
      fetal origin. In vitro propagation of placental mononuclear cell isolates may
      therefore provide populations of maternal CD3+ lymphocytes for assessment of
      function and specificity.

PMID- 8271237
TI  - Phenotypic characterization of normal human placental mononuclear cells.
AB  - The placenta is a rich source of immunocompetent cells. We have studied the
      phenotype, number and origin of placental mononuclear blood cells isolated from
      32 normal term placentae using 4 color flow cytometry. Respective maternal and
      cord blood leucocyte preparations were also compared. Placental tissue without
      extraembryonic membranes was cut into small pieces and divided. One portion was
      washed extensively with ice-cold PBS. Both tissue portions were disrupted in a
      blender and cells were dissociated by using a 180 mu sieve. Leucocytes were
      isolated by Ficoll-Hypaque density gradient centrifugation. Maternal and cord
      bloods were HLA typed and in cases of HLA-A2 or B7/40 disparity, monoclonal anti
      HLA antibodies to these antigens showed that unwashed placental tissue contained
      35% maternal and 65% fetal cells. This ratio, however, was not reflected for a
      given cell phenotype. In comparison, washed placental tissue contained cells of
      fetal origin only. Both unwashed and washed placental tissue contained fewer CD3
      and CD4, but more CD8 cells than maternal and cord blood. Markers of NK cells
      such as, CD16, CD56, and CD57 showed this cellular phenotype to be 15 times more
      abundant in the placental preparations than in cord and maternal blood. The
      quantitative differences between peripheral blood and placental CD8 and NK cells
      were further explored with an antiprogesterone receptor antibody in combination
      with anti-CD8, anti-CD57 and anti-HLA-DR. The number of progesterone receptor
      (PGR) positive cells was three times higher in placental tissues than in cord or
      maternal blood. These data indicate that the phenotypic frequencies of certain
      placental leucocytes are significantly different from maternal and fetal
      peripheral blood. Progesterone and the presence of PGR may be important in the
      differential retention of placental leucocytes.

PMID- 8271238
TI  - Inhibition of DNA synthesis and IL-2 bioactivity in MLR by splenic pregnancy
      associated natural suppressor cells involves the production of a TGF-beta 1-like
      molecule and a second distinct inhibitory factor.
AB  - Natural suppressor cells exhibiting a double-negative, immature T cell phenotype
      have been identified in maternal spleen during syngeneic murine pregnancy. In the
      present study, splenic pregnancy-associated natural suppressor (SPANS) cells are
      shown to express alpha/beta T cell receptors. SPANS cell-mediated inhibition of
      DNA synthesis by spleen cells responding in mixed lymphocyte reactions (MLR) is
      associated with a reduction in interleukin (IL)-2 bioactivity beginning after 96
      h of culture. Although culture supernatants from suppressed MLR exhibit
      diminished ability to support the growth of IL-2-dependent CTLL-2 cells, SPANS
      cells themselves are unable to inhibit IL-2-driven CTLL-2 proliferation,
      suggesting that SPANS cells down-regulate IL-2 synthesis in MLR. IL-2 utilization
      in MLR is also inhibited by SPANS cells, since the addition of exogenous IL-2
      fails to relieve the inhibitory effect of SPANS cells on lymphoproliferative
      responses in MLR. Flow cytofluorometric analysis reveals that MLR performed in
      the presence of SPANS cells contain normal percentages of CD4 and IL-2 receptor
      bearing spleen cells. Thus, SPANS cells do not inhibit cellular proliferation in
      MLR by selectively interfering with clonal expansion of IL-2-producing helper T
      cells or by down-regulating IL-2 receptor expression. We have determined that
      SPANS cells inhibit DNA synthesis in MLR via the production of a transforming
      growth factor (TGF)-beta 1-like suppressor factor, since cellular proliferation
      in MLR is restored to normal levels in the presence of anti-TGF-beta 1
      neutralizing antibody. However, IL-2 bioactivity in these cultures remains low in
      comparison to control MLR, suggesting the presence of a second distinct
      suppressor factor. Although the identity of this second inhibitory molecule has
      yet to be determined, neutralizing antibody studies have ruled out IL-10.

PMID- 8271239
TI  - Mast cells in the Harderian gland of female Syrian hamsters during the estrous
      cycle and pregnancy: effects of the light/dark cycle.
AB  - The number of identifiable mast cells and the intraluminal area occupied by
      porphyrin deposits was studied on semithin sections from female hamster Harderian
      glands during the estrous cycle and pregnancy. Although the serum levels of
      estradiol, progesterone, luteinizing hormone and follicle stimulating hormone
      exhibited significant changes throughout the cycle, no correlation between these
      changes and the variations in the number of recognizable mast cells was observed.
      However both during diestrous 1 and proestrous cycles, the number of identifiable
      mast cells was higher at midnight than at noon (in 14 h light:10 h dark
      photoperiod with lights on at 07:00 h). A more exhaustive study revealed the
      presence of 'degranulated mast cells' which were not stained with toluidine blue.
      Thus, a diurnal cycle in degranulation might occur in the Harderian glands from
      female hamsters. No significant variations were observed in the area occupied by
      intraluminal porphyrin deposits during the estrous cycle. However, both the
      relative number of mast cells and the area occupied by intraluminal porphyrins
      decreased from day 4 of pregnancy to day 14 showing a strong correlation. The
      Harderian glands from female Syrian hamsters might provide a useful model for the
      study of mast cell degranulation during porphyria.

PMID- 8271240
TI  - Suppression of fertility in male mice by immunization against LH receptor.
AB  - We have investigated the potential contraceptive effects of immunization against
      the luteinizing hormone (LH) receptor in male mice at the prepubertal stage. Two
      N-terminal fragments of the porcine LH receptor encoding amino acids 1-297 and 1
      370 were produced in large quantities through the Baculovirus insect cell system.
      We have immunized three-week-old mice from two Balb/c stocks of differing
      fecundity with Sf9 insect cells producing the short (1-297) or long (1-370)
      recombinant LH receptor. A booster injection was performed at six weeks using
      purified antigens. Ten days later, the immunized male mice were mated over a
      period of two weeks with adult untreated females. After weaning of the first
      litters, the same partners were mated once again under the same conditions. There
      was no decrease in the antiserum titers against the antigens over a two-month
      period. The circulating testosterone decreased as the anti-LH receptor antibodies
      increased. The fertility of the treated male mice was reduced up to 75%,
      depending on the mouse stock, the antigen used and the time separating
      immunization and mating. The impaired fertility was mostly due to male
      sterilization (up to 60% of sterile mates). The delay between mating and birth
      was enhanced by the treatment, reflecting delayed fertility and/or delayed male
      behaviour acquisition.

PMID- 8271242
TI  - Dynamic life table model for Aedes aegypti (Diptera: Culicidae): analysis of the
      literature and model development.
AB  - The container-inhabiting mosquito simulation model (CIMSiM) is a weather-driven,
      dynamic life table simulation model of Aedes aegypti (L.). It is designed to
      provide a framework for related models of similar mosquitoes which inhibit
      artificial and natural containers. CIMSiM is an attempt to provide a mechanistic,
      comprehensive, and dynamic accounting of the multitude of relationships known to
      play a role in the life history of these mosquitoes. Development rates of eggs,
      larvae, pupae, and the gonotrophic cycle are based on temperature using an enzyme
      kinetics approach. Larval weight gain and food depletion are based on the
      differential equations of Gilpin & McClelland compensated for temperature.
      Survivals are a function of weather, habitat, and other factors. The
      heterogeneity of the larval habitat is depicted by modeling the immature cohorts
      within up to nine different containers, each of which represents an important
      type of mosquito-producing container in the field. The model provides estimates
      of the age-specific density of each life stage within a representative 1-ha area.
      CIMSiM is interactive and runs on IBM-compatible personal computers. The user
      specifies a region of the world of interest; the model responds with lists of
      countries and associated cities where historical data on weather, larval habitat,
      and human densities are available. Each location is tied to an environmental file
      containing a description of the significant mosquito-producing containers in the
      area and their characteristics. In addition to weather and environmental
      information, CIMSiM uses biological files that include species-specific values
      for each of the parameters used in the model. Within CIMSiM, it is possible to
      create new environmental and biological files or modify existing ones to allow
      simulations to be tailored to particular locations or to parameter sensitivity
      studies. The model also may be used to evaluate any number and combination of
      standard and novel control methods.

PMID- 8271241
TI  - Phenotypic characteristics of lymphoid populations of middle gestation human
      fetal liver, spleen and thymus.
AB  - Mononuclear cells isolated from liver, spleen and thymus of fetuses between 18
      and 24 weeks gestational age were stained for a number of lymphoid cell markers
      by indirect immunofluorescence and analyzed by flow cytometry. Studies were
      carried out on freshly isolated mononuclear cell preparations and on cultured
      cells after selective expansion in interleukin 2 (IL2). Many mononuclear cells in
      fresh isolates of liver and spleen could not be identified with antibodies to
      mature T- and B-cell markers. An average of 3% of isolated liver cells and 34% of
      isolated spleen cells stained positively for CD3, and 19% of liver cells and 37%
      of spleen cells stained positively for CD20. Lymphoid cells of the fetal thymus
      were an average 67% CD3+, 76% CD4+, 84% CD8+, and showed greater CD45RO staining
      (93%) than mononuclear cells of other tissues. Propagation of liver and spleen
      cell populations in culture favored CD3 phenotypes and CD8 phenotypes. Propagated
      T cell populations of liver and spleen were primarily TCR alpha/beta+ (81% in
      liver, 85% in spleen), suggesting a selective advantage in IL2 expansion of
      alpha/beta T cells over gamma/delta T cells. Propagated gamma/delta T cells of
      liver and spleen were predominantly TCR gamma/delta 2+. Whereas propagated cells
      of liver and spleen consisted of approximately 10% gamma/delta+ cells, thymus
      derived cells expanded in culture were only an average of 2% TCR gamma/delta+,
      demonstrating a rarity of IL2-responsive gamma/delta T cells in middle gestation
      fetal thymus.

PMID- 8271243
TI  - Dynamic life table model for Aedes aegypti (diptera: Culicidae): simulation
      results and validation.
AB  - The container-inhabiting mosquito simulation model (CIMSiM) is a weather-driven,
      dynamic life table simulation model of Aedes aegypti (L.) and similar
      nondiapausing Aedes mosquitoes that inhabit artificial and natural containers.
      This paper presents a validation of CIMSiM simulating Ae. aegypti using several
      independent series of data that were not used in model development. Validation
      data sets include laboratory work designed to elucidate the role of diet on
      fecundity and rates of larval development and survival. Comparisons are made with
      four field studies conducted in Bangkok, Thailand, on seasonal changes in
      population dynamics and with a field study in New Orleans, LA, on larval habitat.
      Finally, predicted ovipositional activity of Ae. aegypti in seven cities in the
      southeastern United States for the period 1981-1985 is compared with a data set
      developed by the U.S. Public Health Service. On the basis of these comparisons,
      we believe that, for stated design goals, CIMSiM adequately simulates the
      population dynamics of Ae. aegypti in response to specific information on weather
      and immature habitat. We anticipate that it will be useful in simulation studies
      concerning the development and optimization of control strategies and that, with
      further field validation, can provide entomological inputs for a dengue virus
      transmission model.

PMID- 8271244
TI  - Potential role of cattle egrets, Bubulcus ibis (Ciconiformes: Ardeidae), in the
      dissemination of Amblyomma variegatum (Acari: Ixodidae) in the eastern Caribbean.
AB  - The potential role of cattle egrets, Bubulcus ibis (L.), in the dissemination of
      Amblyomma variegatum (F.) in the eastern Caribbean was evaluated. The status of
      cattle egrets as hosts for A. variegatum in Antigua was determined during seven
      survey periods between September 1988 and May 1991. The mean prevalences of
      infestation by larvae and nymphs were 2.3 and 0.5%, respectively. The mean
      intensity and relative density of infestation by larvae were 8.8 (SD = 9.80) and
      0.2 (SD = 0.28), respectively. Cattle egrets examined in Guadeloupe during
      February-March 1991 were not infested but 5.9% were infested by larvae during
      June-July 1991. Interisland movement of cattle egrets was evaluated relative to
      emigration of birds captured and marked in Antigua and Guadeloupe. During this
      aspect of the study, 1,129 cattle egrets were captured, marked, and released. Of
      195 sighting reports received, 56 were determined to be independent sightings.
      Emigration of cattle egrets included movement of birds marked in Antigua or
      Guadeloupe to 14 Caribbean islands and the Florida Keys. Interisland movement
      occurred in each of the discrete observation periods during the 3-yr study
      period. The rate of emigration per period ranged from 1.2 to 12.9%. That cattle
      egrets served as hosts for immature A. variegatum in the eastern Caribbean and
      moved between islands in the region demonstrates that these birds could serve as
      disseminators of the tick. Estimates of the numbers of infested cattle egrets
      emigrating from Antigua and Guadeloupe ranged from 0 to 0.24% of the current
      populations.

PMID- 8271245
TI  - Short-term changes in the abundance and parity rate of Anopheles quadrimaculatus
      species C (Diptera: Culicidae) in a central Florida swamp.
AB  - Updraft CDC traps baited with dry ice were used to monitor changes in the
      abundance and parity rate of Anopheles quadrimaculatus Say complex mosquitoes in
      an intermittently flooded swamp in Central Florida during an 18-d period.
      Mosquitoes collected each day were identified to species using DNA hybridization
      and isozyme electrophoretic techniques and were dissected to determine follicular
      maturation and parity. Of 1,178 An. quadrimaculatus mosquitoes identified to
      species, 4% were species A and 96% were species C. Dissections of females of both
      species indicated that 98% were nonblood fed and nongravid with ovariole
      development at Christophers' stage II. Overall parity rates were 0.19 and 0.51
      for populations of species A and species C, respectively. The duration of the
      gonotrophic cycle for species C females was estimated to be 5 d based on the
      interval between peaks in the number of nulliparous females collected on days 1
      and 6 and peaks in the number of parous females collected 5 d later. Significant
      trends were observed in the number of parous species C females collected each
      day, indicating that the parity rate could not be used as an unbiased estimator
      of survivorship.

PMID- 8271246
TI  - Reduced abundance of Ixodes scapularis (Acari: Ixodidae) and Lyme disease risk by
      deer exclusion.
AB  - The effect of deer exclosures upon the numbers of immature Ixodes scapularis Say,
      the vector of Lyme disease in the eastern United States, was examined at five
      sites in Westchester County, NY. Study areas ranged in size from 6 to 101 ha
      where deer had been excluded for a period of 25 yr by > 2.4-m-high fencing that
      surrounded each site. A total area of 40,506 m2 was drag-sampled during the study
      to measure tick abundance. Nymphal densities (ticks per 1,000 m2) averaged 4.6
      (range, 1.3-9.6) inside exclosures and 27.7 (range, 7.3-79.4) outside. Larval
      densities averaged 36.7 (range, 1.2-132.1) inside exclosures and 354.4 (range,
      7.5-914.5) outside. Comparisons between exclosure sites and outside areas
      immediately adjacent to the exclosure fence, where deer had unrestricted access,
      revealed that exclosures had 83% fewer host-seeking nymphs and 90% fewer host
      seeking larvae. Tick numbers inside exclosures did not always decline with
      increasing distance from the fence. There was no significant difference in the
      rate of Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner
      infection for host-seeking ticks collected inside (20%, n = 50) exclosures
      compared with ticks collected outside (26%, n = 50) exclosures. Deer fencing may
      provide a means of significantly reducing the abundance of I. scapularis and the
      risk of Lyme disease in relatively large areas without the need to reduce or
      eliminate the deer population.

PMID- 8271247
TI  - Bacterial enrichment in the surface microlayer of an Anopheles quadrimaculatus
      (diptera: culicidae) larval habitat.
AB  - Sampling of the surface microlayer of water in a marsh habitat of Anopheles
      quadrimaculatus Say in Michigan revealed it to be enriched with bacteria compared
      with subsurface water samples. Concentrations of total numbers of bacteria ranged
      from 18.8 x 10(6)/ml to 65.4 x 10(6)/ml (mean, 35.9 x 10(6)/ml; n = 13) in
      surface microlayer samples, and from 3.8 x 10(6)/ml to 14.3 x 10(6)/ml, (mean,
      7.8 x 10(6)/ml; n = 13) in subsurface samples. Specifically, the surface
      microlayer had higher concentrations of three morphotypes of bacteria (cocci,
      rods, and rods attached to detritus particles). Given that bacteria are an
      important food of mosquito larvae, we suggest that the interfacial feeding
      behavior of An. quadrimaculatus larvae allows them to exploit the surface
      microlayer, a food-rich zone.

PMID- 8271248
TI  - Effect of light trap height on catch of Culicoides (Diptera: Ceratopogonidae) in
      Israel.
AB  - Vertical suction light trapping was conducted in 1981 at two dairy farms, Bet
      Dagan (traps at 1.4 and 26 m above ground) and Bet Alfa (traps at 1.5 and 20 m).
      Of the nine Culicoides species caught in both localities, only C. circumscriptus
      Kieffer and C. cataneii Clastrier showed a significant difference in abundance
      related to trap height; C. imicola Kieffer and C. schultzei sp. gp. also
      demonstrated a height preference, but catch sizes did not differ statistically.
      C. circumscriptus and C. cataneii, both avian feeders, and C. imicola, a
      mammalian feeder, were caught in greater numbers in the higher than in the lower
      traps. In contrast, more C. schultzei sp. gp. females were caught in lower than
      higher traps. Species collected more frequently in higher traps may be more prone
      to carriage for long distances by air currents and therefore are more likely to
      be important as dispersal vectors.

PMID- 8271249
TI  - Feeding nymphs of Hyalomma truncatum (Acari: Ixodidae) on guinea pigs previously
      exposed to nymphs.
AB  - The ability of nymphal Hyalomma truncatum Koch to feed on guinea pigs previously
      exposed to nymphal ticks was studied by measuring the percentage of ticks
      engorging and molting, their engorged weight, and hemoglobin content. Four guinea
      pigs were infested with 20, 40, 80, and 200 nymphs, respectively, on three
      occasions at 21-d intervals, followed by a fourth infestation after another 21-d
      interval with 100 nymphs. Guinea pigs originally infested with 20 and 80 nymphs
      were infested a fifth time with 100 nymphs 3 mo after the fourth infestation.
      Guinea pigs originally infested with 40 and 200 nymphs were infested a fifth time
      with 100 nymphs 6 mo after the fourth infestation. There was a significant
      decrease, below infestation I levels, in the number of ticks engorging on each
      guinea pig during infestations IV and V. Whereas all nymphs molted after
      infestation I, the percentage of nymphs molting after infestation V ranged from 0
      to 34%. For ticks infested on each of the guinea pigs, the percentage molting
      after infestations III-V were significantly lower than those observed after
      infestation I. A significant decrease in the mean weight of engorged ticks was
      observed starting at infestation III. Mean hemoglobin content of ticks declined
      significantly at infestation II. The response elicited by feeding nymphs appeared
      to last at least 6 mo.

PMID- 8271250
TI  - Ectoparasites of some wild rodents from Parana State, Brazil.
AB  - Forty-four cricetid rodents belonging to four species from Parana State, Brazil,
      were karyotyped and examined for ectoparasites. Thirteen species of
      ectoparasites, including five mites, one louse, and seven fleas, are recorded for
      the first time from Parana. New host records are described for four species of
      mites, one sucking louse, and seven fleas.

PMID- 8271251
TI  - Mark and recapture of adult Ixodes pacificus (Acari: Ixodidae) to determine the
      effect of repeated removal sampling on tick abundance.
AB  - The effect of biweekly flagging on adult Ixodes pacificus Cooley & Kohls
      abundance was determined by using mark-recapture techniques. Ticks were
      recaptured up to three times during the 12-wk study, and increasingly higher
      proportions of marked ticks were recaptured as the study progressed. By week 6 of
      the study, 46% of the collected ticks had been marked, and on the final sampling
      date, all ticks had been captured previously. Removal sampling would have
      substantially reduced estimates of the abundance of the questing I. pacificus
      adult population. For ecological studies that require the repeated sampling of a
      given habitat, the most representative data are obtained by returning flagged
      ticks to their collection site.

PMID- 8271252
TI  - Haemaphysalis juxtakochi Cooley (Acari: ixodidae), a neotropical tick species,
      found in Ohio.
AB  - Haemaphysalis juxtakochi Cooley, 1946, an ectoparasite of deer and other large
      mammals from Mexico southward through Central and South America, was recovered
      from the ear of a white-tailed deer, Odocoileus virginanus Zimmermann, in Ohio.
      This represents the first record of H. juxtakochi from the United States.

PMID- 8271253
TI  - Kinetics of male pheromone production by Amblyomma variegatum (Acari: Ixodidae).
AB  - Males of Amblyomma variegatum (F.), when attached on their host, produce a
      pheromonal blend composed of methyl salicylate, ortho-nitrophenol, and nonanoic
      acid, which acts as an aggregation-attachment pheromone. Using olfactometry
      assays, assays on hosts, and quantification of the compounds by capillary gas
      chromatography, the kinetics of pheromone production has been studied. Males
      engorged for at least 10 d elicit attachment from most of the tested females.
      Attractiveness of males for females is significant only between days 14 and 23 of
      engorgement. Before 10 d of attachment, the amounts of pheromones detected in
      hexanic male body extracts are very low (< 10 ng); they then increase to a
      maximum of 2 micrograms for the major compound per male. Large amounts can be
      detected until 80 d of engorgement. The inter-individual variation is very large
      throughout the engorgement period. The interest and the limitations of the
      different techniques used are discussed.

PMID- 8271254
TI  - Haemaphysalis suntzovi, a new species of ixodid tick (Acari) from vietnam.
AB  - Haemaphysalis suntzovi Kolonin, n. sp. is described from males and females
      collected on the porcupine Hystrix brachyura L., boar, Sus scrofa L., and
      vegetation from Vietnam. This new species is closely related to Haemaphysalis
      roubaudi Toumanoff and species of the subgenus Aborphysalis.

PMID- 8271255
TI  - Survey of the Anopheles maculatus complex (Diptera: Culicidae) in peninsular
      Malaysia by analysis of cuticular lipids.
AB  - Anopheles maculatus Theobald sensu lato is a species complex now consisting of
      eight sibling species; An. maculatus is still represented by two cytologically
      distinct forms; i.e., the widely distributed sensu strictu or B, and E from
      southern Thailand and adjacent areas in northern Malaysia. Cuticular lipid
      profiles in conjunction with principal component analysis was used to separate
      An. maculatus form E from sensu stricto form B in a preliminary survey of the An.
      maculatus complex at five locations spanning peninsular Malaysia. The relative
      rank orders, from the areas of the five gas chromatographic peaks used to
      determine lipid differences for specimens from peninsular Malaysia, matched well
      with those from cytogenetically identified colony specimens of An. maculatus
      forms B and E. The two-dimensional principal component pattern of specimens
      identified as form E was highly clumped, which indicated that very similar
      cuticular lipids were present within this putative malaria vector. Both forms
      coexisted in peninsular Malaysia, but form E may be dominant except in the south.

PMID- 8271256
TI  - Multiple blood meals as a reproductive strategy in Anopheles (Diptera: Culicidae)
AB  - Multiple blood meals within one gonotrophic cycle were taken readily at 6-24-hr
      intervals by nulliparous female Anopheles albimanus Wiedemann. Up to five blood
      meals were ingested and with each blood meal, more primary follicles matured as
      well as some secondary ones. This produced an irregular oviposition pattern that
      questioned the concept of gonotrophic concordance. The first blood meal initiated
      limited vitellogenesis and the maturation of few follicles. Instead, protein was
      diverted to the synthesis of maternal, extraovarian lipid and protein deposits;
      fecundity increased with successive blood meals. This pattern of protein and
      energy utilization may be explained in terms of the low caloric lipid and protein
      content of nulliparous females before the first blood meal. In An. albimanus, a
      critical female body size, approximately 0.25 cal of lipid per female, was
      necessary for the initiation of oogenesis; below this threshold at least two
      blood meals were required for follicle maturation. Less than 10% of the caloric
      input from a blood meal was utilized in the synthesis of ovarian protein and
      lipids, whereas a similar percentage was transferred to maternal deposits of
      protein and lipid. In nonoogenic females, a replete blood meal increased total
      body protein and lipid by 17 and 113%, respectively. Altogether, the efficiency
      of blood protein utilization was rather low, as indicated by losses of excretory
      nitrogen that regularly exceeded 75% of the input. Anopheles gambiae Giles and
      An. stephensi Liston also fed multiply, but fecundity was less affected. Instead,
      maternal deposits were synthesized from the blood meal in substantial amounts. In
      general, gonotrophic discordance also was found routinely in these anopheline
      species. The ratio of yolk protein to lipids varied inter- and intra
      specifically, as well as among consecutive blood meals, indicating a considerable
      plasticity in the caloric distribution of these two yolk components.

PMID- 8271257
TI  - Reduced abundance of Ixodes scapularis (Acari: Ixodidae) with exclusion of deer
      by electric fencing.
AB  - To assess the effect of deer exclusion on populations of Ixodes scapularis Say
      (formerly I. dammini Spielman, Clifford, Piesman & Corwin) in the northeastern
      United States, host-seeking ticks and ticks on white-footed mice, Peromyscus
      leucopus (Rafinesque), were monitored inside and outside a wooded, residential
      deer exclosure (approximately 3.5 ha) in Lyme, CT, in 1991 and 1992. Another deer
      exclosure was added in Lyme (approximately 7.4 ha) during 1992. Additional sample
      sites at other residences served as secondary controls. A seven-wire, slanted,
      high-tensile electric deer fence was used at both areas. Larvae of I. scapularis
      were 81.5% (1991) and 97.8% (1992) less abundant within the exclosure than
      immediately outside the deer exclosures. Nymphs of I. scapularis were 47.4%
      (1991) and 55.8% (1992) less abundant within the deer fence. The effect on adult
      ticks was mixed. No difference in tick abundance was seen at the 3.5-ha site.
      However, larvae, nymphs, and adults were 100, 83.8, and 74.1% less abundant,
      respectively, in plots at the 7.4-ha exclosure > or = 70 m from the deer fence
      and isolated from woodlands outside the fence by lawns, driveways, and buildings.
      The recovery of larvae and nymphs of I. scapularis from mice captured within the
      deer exclosures indicates that infestations of nymphs and adults are probably, at
      least in part, a result of the movement of these rodents. Based upon the number
      of nymphs per 100 m2 infected with Borrelia burgdorferi Johnson, Schmid, Hyde,
      Steigerwalt & Brenner, the causal agent of Lyme disease, there were 73 and 82%
      fewer infected nymphs within the deer exclosures in 1992 in comparison with the
      number of infected ticks outside the fence and at the secondary control sites,
      respectively. The exclusion of deer in conjunction with other tick control
      strategies in large areas could substantially reduce populations of I. scapularis
      and the risk of acquiring Lyme disease.

PMID- 8271258
TI  - Stagewise mortality, ovipositional biology, and egg viability of Boophilus
      annulatus (Acari: Ixodidae) on Boselaphus tragocamelus (Artiodactyla: Bovidae).
AB  - The stagewise mortality, ovipositional biology, and egg viability of the cattle
      tick, Boophilus annulatus (Say), on nilgai antelope, Boselaphus tragocamelus
      Pallas, was compared with ticks reared on Bos taurus (Hereford) cattle. Mortality
      was highest during the larval stage on both host species, but larval mortality on
      nilgai (78.6%) was significantly higher than on cattle (45.6%) hosts. Mortality
      during the nymphal stage was also significantly higher on nilgai (49.3%) than on
      cattle (13.9%). During adult female development, although the mortality rate on
      nilgai was 40.9% compared with no mortality of females on cattle, this difference
      was not significant. Significantly fewer ticks reached repletion on nilgai (4.0
      females per animal) than on cattle (48.5 females per animal). The mean female
      weight and egg mass weight of ticks obtained from cattle were significantly
      higher than ticks produced from nilgai. On the other hand, no differences in mean
      conversion efficiency index (CEI), preoviposition period, incubation period, or
      egg hatch were observed among ticks obtained from the two host animals. Although
      nilgai produce fewer replete females, and the females that do survive are smaller
      and produce smaller egg masses, nilgai cannot be disregarded in an eradication
      program. The fact that even a small number of viable ticks is able to reproduce
      successfully on nilgai could lead to the failure of current eradication
      strategies by compromising the required quarantine interval.

PMID- 8271260
TI  - Vasopressin-dependent control of basolateral Na/H-exchange in highly
      differentiated A6-cell monolayers.
AB  - We have used a well-differentiated A6-cell preparation (A6-C1) to study cellular
      location and vasopressin control of Na/H-exchange activity. After cell
      acidification, cell pHi (measured by BCECF-fluorescence) only recovered by the
      addition of Na medium to the basolateral cell surface; this pHi recovery was
      inhibited by dimethylamiloride (2 microM) consistent with basolateral location of
      Na/H-exchange activity. Addition of vasopressin produced stimulation of Na/H
      exchange activity and increased the affinity of the exchanger for Na+.
      Stimulation of Na/H exchange was mimicked by pharmacological activation of
      protein kinase A (forskolin, 8-Br-cAMP) and not by pharmacological activation of
      protein kinase C (TPA). It is concluded that basolaterally located Na/H-exchange
      in A6-C1 cells is activated by vasopressin.

PMID- 8271259
TI  - Mitochondrial protein import: specific recognition and membrane translocation of
      preproteins.

PMID- 8271261
TI  - Riboflavin uptake by rat small intestinal brush border membrane vesicles: a dual
      mechanism involving specific membrane binding.
AB  - The first step of riboflavin absorption was studied by determining the uptake of
      the vitamin by rat small intestinal brush border membrane vesicles. Vesicles were
      incubated at 25 degrees C in the presence of [3H]-riboflavin at concentrations
      within the physiological intraluminal range for rat. The time course of [3H]
      riboflavin uptake was unaffected by Na+ or K+ gradients. The 5 sec uptake rate
      plotted as a function of the initial concentration of [3H]-riboflavin in the
      medium (0.125 to 7.5 microM) revealed the presence of a dual mechanism, with a
      saturable component (apparent kinetic constants: 0.12 microM for Km and 0.36
      pmol.mg-1 protein x 5 sec-1 for Jmax) prevailing at low concentrations (< 2
      microM), and a nonsaturable component prevailing at higher concentrations. The
      presence of a carrier-mediated system for riboflavin was validated by
      countertransport experiments. At equilibrium, uptake was almost completely
      accounted for by membrane binding, whereas at earlier times the transport
      component accounted for about 30% of total uptake. The plot of [3H]-riboflavin
      binding at equilibrium as a function of its concentration in the medium was quite
      similar to that of the 5 sec uptake rate in both intact and osmotically shocked
      vesicles and demonstrated the occurrence of a saturable component: binding
      constants were 0.07 (Kd in microM), 0.54 (Bmax in pmol.mg-1 protein), and 0.11
      (Kd), 1.13 (Bmax), respectively, indicating the existence of specific riboflavin
      binding sites. The specificity of riboflavin binding to the membrane was
      confirmed by preliminary studies with structural analogues. Specific binding
      could represent the first step of a specific riboflavin entry mechanism in
      enterocytes.

PMID- 8271262
TI  - Differential arrival of newly synthesized apical and basolateral plasma membrane
      proteins in the epithelial cell line A6.
AB  - The labeling of specific cell surface proteins with biotin was used to examine
      both protein distribution and delivery of newly synthesized proteins to the
      apical and basolateral cell surface in A6 cells. Steady-state metabolic labeling
      with [35S]methionine followed by specific cell surface biotinylation demonstrated
      polarization of membrane proteins. The delivery of newly synthesized proteins to
      the apical or basolateral cell surface was examined by metabolic labeling with
      [35S]methionine using a pulse-chase protocol in combination with specific cell
      surface biotinylation. Newly synthesized biotinylated proteins at the apical cell
      surface reached a maximum after a 5 min chase, and then fell over the remainder
      of a 2 hr chase. The bulk flow of newly synthesized proteins to the basolateral
      membrane slowly rose to a maximum after 90 min. The detergent Triton X-114 was
      used to examine delivery of hydrophilic and hydrophobic proteins to the cell
      surface. Delivery of both hydrophilic and hydrophobic proteins to the apical cell
      surface reached a maximum 5 to 10 min into the chase period. The arrival of
      hydrophilic proteins at the basolateral surface showed early delivery and a
      maximum peak delivery at 120 min into the chase period. In contrast, only an
      early peak of delivery of newly synthesized hydrophobic proteins to the
      basolateral membrane was observed.

PMID- 8271263
TI  - Redistribution of hepatocyte chloride during L-alanine uptake.
AB  - We used ion-sensitive, double-barrel microelectrodes to measure changes in
      hepatocyte transmembrane potential (Vm), intracellular K+, Cl-, and Na+
      activities (aiK, aiCl and aiNa), and water volume during L-alanine uptake. Mouse
      liver slices were superfused with control and experimental Krebs physiological
      salt solutions. The experimental solution contained 20 mM L-alanine, and the
      control solution was adjusted to the same osmolality (305 mOsm) with added
      sucrose. Hepatocytes also were loaded with 50 mM tetramethylammonium ion (TMA+)
      for 10 min. Changes in cell water volume during L-alanine uptake were determined
      by changes in intracellular, steady-state TMA+ activity measured with the K+
      electrode. Hepatocyte control Vm was -33 +/- 1 mV. L-alanine uptake first
      depolarized Vm by 2 +/- 0.2 mV and then hyperpolarized Vm by 5 mV to -38 +/- 1 mV
      (n = 16) over 6 to 13 min. During this hyperpolarization, aiNa increased by 30%
      from 19 +/- 2 to 25 +/- 3 mM (P < 0.01), and aiK did not change significantly
      from 83 +/- 3 mM. However, with added ouabain (1 mM) L-alanine caused only a 2-mV
      increase in Vm, but now aiK decreased from 61 +/- 3 to 54 +/- 5 mM (P < 0.05).
      Hyperpolarization of Vm by L-alanine uptake also resulted in a 38% decrease of
      aiCl from 20 +/- 2 to 12 +/- 3 mM (P < 0.001). Changes in Vm and VCl-Vm voltage
      traces were parallel during the time of L-alanine hyperpolarization, which is
      consistent with passive distribution of intracellular Cl- with the Vm in
      hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271264
TI  - Do independent processes control the activation and inactivation of potassium
      contracture tension in rat skeletal muscle?
AB  - Potassium (K+) contracture tension, measured in small bundles of rat soleus
      muscle fibers during maintained depolarization, increases to a peak value and
      then decays either to the baseline or to a pedestal level. We have tested the
      hypothesis that the rise and fall of tension are determined by independent
      activation and inactivation processes. If the "Independence" hypothesis is
      correct, tension during the decay of K+ contractures should equal tension
      predicted from the product of the activation and inactivation parameters
      determined from the same K+ contractures. Both the measured and predicted
      tensions decayed to a pedestal level that was increased in amplitude in the
      presence of perchlorate ions. However, the measured tensions in normal solutions
      and in the presence of perchlorate were three to five times smaller than the
      predicted tensions. This result indicates that the activation and inactivation of
      processes controlling the rise and decay of K+ contracture tension are not
      independent.

PMID- 8271265
TI  - Electrical responses of the marine ciliate Euplotes vannus (hypotrichia) to
      mechanical stimulation at the posterior cell end.
AB  - Electrical responses upon mechanostimulation at the posterior cell end were
      investigated in the marine hypotrichous ciliate Euplotes vannus. A new
      mechanostimulator was developed to mimic stimuli that are identical with those
      involved in cell-cell collisions. The receptor potential hyperpolarized by 18-35
      mV within 12-25 msec, reached a peak value of -62 mV with a delay of 4-9 msec
      after membrane deformation, and was deactivated after 50-70 msec. Cirri were
      stimulated to beat accelerated backward. The corresponding receptor current
      exerted a similar time course with a peak of 2.4 nA. The shift of the reversal
      potential by 57.6 mV at a tenfold increase of [K+]o identifies potassium ions as
      current carriers within the development of the receptor potential. An
      intracellular K concentration of 355 mmol/liter was calculated for cells in a
      medium that was composed similar to sea-water. The mechanically activated
      potassium current was totally inhibited by extracellular TEA and intracellular
      Cs+, and partially inhibited by extracellular 4-AP. The total inhibition of the
      current by injected EGTA points to a Ca dependence of the posterior
      mechanosensitivity. It was confirmed by the increase of the peak current
      amplitude with rising [Ca2+]o. Sodium presumably repolarizes the receptor
      potential because the repolarization was delayed and after-depolarizations were
      eliminated in media without sodium. Since deciliation did not affect
      mechanosensitivity, the corresponding ion channels reside within the soma
      membrane.

PMID- 8271266
TI  - A Ca(2+)-activated Cl- current in sheep parotid secretory cells.
AB  - Previous studies have shown that the whole-cell current-voltage (I-V) relation of
      unstimulated sheep parotid cells is dominated by two K+ conductances, one
      outwardly and the other inwardly rectifying. We now show that once these K+
      conductances are blocked by replacement of pipette K+ with Na+ and by the
      addition of 5 mmol/liter CsCl to the bath, there remains an outwardly rectifying
      conductance with a reversal potential of 0 mV. Replacement of 120 mmol/liter NaCl
      in the pipette solution with an equimolar amount of Na-glutamate shifted the
      reversal potential of this residual current to -55 mV, indicating that the
      conductance was Cl- selective. The Cl- current was activated by increasing the
      free Ca2+ in the pipette solution from 10 to 100 nmol/liter. When the Ca2+
      concentration in the pipette solution was 10 nmol/liter, the relaxations observed
      in response to membrane depolarization could be fitted with a single exponential,
      whose time constant increased from 81 to 183 ms as the pipette potential was
      increased from -30 to +60 mV. Relaxation analysis showed that the current was
      activated by membrane depolarization. Reversal potential measurements in
      experiments in which external Cl- was replaced with various anions, gave the
      following relative permeabilities: SCN- (1.80) > I- (1.09) > Cl- (1) > NO3-
      (0.92) > Br- (0.75). The relative conductances were: SCN- (2.18) > I- (1.07) > Cl
      (1.00) > Br- (0.91) > NO3- (0.50). The Cl- current was blocked by NPPB (ID50
      approximately 10 microM), DIDS (10 or 30 mumol/liter) and furosemide (100
      mumol/liter).

PMID- 8271267
TI  - Mobilization of intracellular calcium in cultured vascular smooth muscle cells by
      uridine triphosphate and the calcium ionophore A23187.
AB  - The known action of uridine triphosphate (UTP) to contract some types of vascular
      smooth muscle, and the present finding that it is more potent than adenosine
      triphosphate in eliciting an increase in cytosolic Ca2+ concentration in aortic
      smooth muscle, led us to investigate the mode of action of this nucleotide. With
      this aim, cultured bovine aorta cells were subjected to patch-clamp methodologies
      under various conditions. Nucleotide-induced variations in cytosolic Ca2+ were
      monitored by using single channel recordings of the high conductance Ca(2+)
      activated K+ (Maxi-K) channel within on-cell patches as a reporter, and whole
      cell currents were measured following perforation of the patch. In cells bathed
      in Na(+)-saline, UTP (> 30 nM) induced an inward current, and both Maxi-K channel
      activity and unitary current amplitude of the Maxi-K channel transiently
      increased. Repetitive exposures elicited similar responses when 5 to 10 min wash
      intervals were allowed between challenges of nucleotide. Oscillations in channel
      activity, but not oscillation in current amplitude were frequently observed with
      UTP levels > 0.1 microM. Cells bathed in K+ saline (150 mM) were less sensitive
      to UTP (approximately 5-fold), and did not show an increase in unitary Maxi-K
      current amplitude. Since the increase in amplitude occurs due to depolarization
      of the cell membrane, a change in amplitude was not observed in cells previously
      depolarized with K+ saline. The enhancement of Maxi-K channel activity in the
      presence of UTP was not diminished by Ca2+ entry blockers or by removal of
      extracellular Ca2+. However, in the latter case, repetitive responses
      progressively declined. These observations, as well as data comparing the action
      of low concentrations of Ca2+ ionophores (< 5 microM) to that of UTP indicate
      that both agents elevate cytosolic Ca2+ by mobilization of this ion from
      intracellular pools. However, the Ca2+ ionophore did not cause membrane
      depolarization, and thus did not change unitary current amplitude. The effect of
      UTP on Maxi-K channel activity and current amplitude was blocked by pertussis
      toxin and by phorbol 12-myristate 13-acetate (PMA), but was not modified by
      okadaic acid, or by inhibitors of protein kinase C (PKC). Our data support a
      model in which a pyrimidinergic receptor is coupled to a G protein, and this
      interaction mediates release of Ca2+ from intracellular pools, presumably via the
      phosphatidyl inositol pathway. This also results in activation of membrane
      channels that give rise to an inward current and depolarization. Ultimately,
      smooth muscle contraction ensues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8271268
TI  - Na+ and Cl- conductances are controlled by cytosolic Cl- concentration in the
      intralobular duct cells of mouse mandibular glands.
AB  - Our previously published whole-cell patch-clamp studies on the cells of the
      intralobular (granular) ducts of the mandibular glands of male mice revealed the
      presence of an amiloride-sensitive Na+ conductance in the plasma membrane. In
      this study we demonstrate the presence also of a Cl- conductance and we show that
      the sizes of both conductances vary with the Cl- concentration of the fluid
      bathing the cytosolic surface of the plasma membrane. As the cytosolic Cl-
      concentration rises from 5 to 150 mmol/liter, the size of the inward Na+ current
      declines, the decline being half-maximal when the Cl- concentration is
      approximately 50 mmol/liter. In contrast, as cytosolic Cl- concentration
      increases, the inward Cl- current remains at a constant low level until the Cl-
      concentration exceeds 80 mmol/liter, when it begins to increase. Studies in which
      Cl- in the pipette solution was replaced by other anions indicate that the Na+
      current is suppressed by intracellular Br-, Cl- and NO3- but not by intracellular
      I-, glutamate or gluconate. Our studies also show that the Cl- conductance allows
      passage of Cl- and Br- equally well, I- less well, and NO3-, glutamate and
      gluconate poorly, if at all. The findings with NO3- are of particular interest
      because they show that suppression of the Na+ current by a high intracellular
      concentration of a particular anion does not depend on actual passage of that
      anion through the Cl- conductance. In mouse granular duct cells there is, thus, a
      reciprocal regulation of Na+ and Cl- conductances by the cytosolic Cl-
      concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271269
TI  - Structure-function studies on the pore of potassium channels.

PMID- 8271270
TI  - Inward rectification of the minK potassium channel.
AB  - The minK protein induces a slowly activating voltage-dependent potassium current
      when expressed in Xenopus oocytes. We have used macroscopic minK currents to
      determine the open channel current-voltage relationship for the channel, and have
      found that the minK current is inwardly rectifying. The channel passes inward
      current at least 20-fold more readily than outward current. Both rat and human
      minK exhibit this property. The rectification of minK is similar to that reported
      for a slow component of the cardiac delayed rectifier, strengthening the
      hypothesis that minK is responsible for that current.

PMID- 8271271
TI  - Properties of acetylcholine receptors in adult rat skeletal muscle fibers in
      culture.
AB  - The distribution and biophysical properties of acetylcholine receptors were
      studied, using morphological and patch-clamp techniques, in adult rat skeletal
      muscle fibers dissociated by collagenase and maintained in culture. Up to ten
      hours after dissociation, there were no changes in either the distribution or the
      biophysical properties of junctional acetylcholine receptors. In long-term
      culture (5 to 14 days), a new type of acetylcholine receptor was inserted all
      over the muscle fibers; the channel properties were characterized by a longer
      open time and a smaller conductance, similar to what has been observed in in vivo
      denervated muscles. Using autoradiography, we found that during culture an
      impaired incorporation of new acetylcholine receptors in the former endplates
      caused a progressive decrease in the density of junctional acetylcholine
      receptors. This contrasts with muscle fibers denervated in vivo, where the
      density of receptors does not change after denervation.

PMID- 8271272
TI  - Volume regulation in human fibroblasts: role of Ca2+ and 5-lipoxygenase products
      in the activation of the Cl- efflux.
AB  - Trypsinized human skin fibroblasts in suspension perform regulatory volume
      decrease (RVD) after cell swelling in hypotonic medium. During RVD, 36Cl- efflux
      is dramatically increased and the cell membrane is depolarized, indicating the
      activation of Cl- channels. This activation of Cl- channels depends on
      extracellular as well as on intracellular Ca2+. The swelling-induced Cl- efflux
      and the RVD response are inhibited by the 5-lipoxygenase inhibitor ETH 615-139.
      Finally, following hypotonic treatment, cellular pH decreases. The pH decrease
      does not involve the Cl-/HCO3- exchange because it is independent of the external
      Cl- concentration.

PMID- 8271273
TI  - Quantitation of Na+/K(+)-ATPase and glucose transporter isoforms in rat adipocyte
      plasma membrane by immunogold labeling.
AB  - We have quantitated and studied the topology of isoforms of the Na+/K(+)-ATPase
      and of the glucose transporter in rat adipocyte plasma membranes. Adipocytes were
      incubated with or without insulin for 15 min. Sheets of native plasma membrane,
      with the cytoplasmic face exposed, were prepared by adsorption to EM grids. Grids
      were incubated in parallel with monoclonal antibodies against the Na+/K(+)-ATPase
      isoforms alpha 1 and alpha 2, and the glucose transporter isoforms GLUT1 and
      GLUT4, followed by immunogold labeling, negative staining and quantitation by
      counting of the gold particles in electron micrographs. In addition, the
      distribution of glucose transporters and Na+/K(+)-ATPase isoforms in subcellular
      membrane fractions prepared by an established fractionation procedure was
      monitored by Western blotting. We found that the Na+/K(+)-ATPases and the glucose
      transporters were confined to the planar part of the plasma membrane, without
      association to caveolar invaginations. The vast majority of the Na+/K(+)-ATPase
      molecules in the adipocyte plasma membrane were of the alpha 2 isoform; GLUT4 was
      the dominating glucose transporter isoform. The total number of Na+/K(+)-ATPase
      molecules labeled in the plasma membrane was 3.5 x 10(5) per cell, independent of
      insulin stimulation. Concomitantly, insulin increased GLUT4 labeling sevenfold to
      a value of 3.5 x 10(5) per cell.

PMID- 8271274
TI  - Satellite glial cells in situ within mammalian prevertebral ganglia express K+
      channels active at rest potential.
AB  - Patch-clamp experiments were performed on satellite glial cells wrapped around
      sympathetic neurons in the rabbit coeliac ganglion. With the cleaning method
      used, the glial cells could be kept in place and were directly accessible to the
      patch-clamp pipettes. Whole-cell recordings showed that glial cells had almost
      ohmic properties. Their resting potential (-79.1 +/- 1.2 mV) was found to be very
      nearly the same as the K+ reversal potential and approximately 20 mV more
      negative than that of the neurons they encapsulated. Unitary currents from ionic
      channels present in the glial membrane were recorded in the cell-attached
      configuration with pipettes filled with various amounts of K+, Na+ and gluconate.
      Only K(+)-selective channels with slight inwardly rectifying properties (in the
      presence of 150 mM [K+]o) were detected. These channels were active (Po = 0.7
      0.8) at the cell resting potential. The channel conductance, but not its opening
      probability, was dependent on the [K+] in the pipette. Cl(-)-selective channels
      (outwardly rectifying and large conductance channels) were detected in excised
      patches. The properties of the K+ channels (increased inward current with [K+]
      and detectable outward current at low [K+]) are well suited for siphoning the K+
      released by active neurons.

PMID- 8271275
TI  - Top cancer-related news stories focus on breast, prostate, and colon cancers.

PMID- 8271276
TI  - NCI replaces guidelines with statement of evidence.

PMID- 8271277
TI  - Heterocyclic amines in cooked foods: candidates for causation of common cancers.

PMID- 8271278
TI  - Genotoxicity and carcinogenicity in rats and mice of 2-amino-3,6-dihydro-3-methyl
      7H-imidazolo[4,5-f]quinolin-7- one: an intestinal bacterial metabolite of 2-amino
      3-methyl-3H-imidazo[4,5-f]quinoline.
AB  - BACKGROUND: Compounds formed on the surface of fried or grilled meat and fish may
      be associated with increased risk of colon cancer. Normal intestinal bacteria can
      convert one of these compounds, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ),
      to the 7-hydroxy metabolite, 2-amino-3,6-dihydro-3-methyl-7H-imidazolo[4,5
      f]quinolin-7-o ne (7-OHIQ), a direct-acting mutagen. PURPOSE: We studied the
      genotoxicity and carcinogenicity of 7-OHIQ to determine if it is responsible for
      the colon-specific activity of IQ. METHODS: The effects of pure, synthetic 7-OHIQ
      on DNA were evaluated in the Ames Salmonella typhimurium TA98 test, with and
      without an induced rat liver S9 fraction, and in the Williams DNA repair test
      using freshly explanted rat hepatocytes. 7-OHIQ was also subjected to an in vivo
      bioassay for 21 months by long-term intrarectal infusion in male F344 rats, using
      IQ and N-nitrosomethylurea (NMU) given intrarectally as positive tumor-producing
      controls. The standard NIH-07 rodent diet was supplemented with 15% corn oil to
      maximize any effect of the infused materials on the colon. A parallel bioassay
      involved intraperitoneal injection of 7-OHIQ in newborn mice, followed by dietary
      administration from week 11 to week 67. Again, IQ and NMU were used as positive
      controls. RESULTS: We confirmed that 7-OHIQ is a direct-acting mutagen in the
      Ames test, with added S9 liver fraction giving higher mutagenicity. 7-OHIQ was
      negative in the Williams test, whereas IQ was positive. 7-OHIQ did not induce
      colon cancer in rats, and in the newborn mouse test it produced only a low
      incidence of liver neoplasms. CONCLUSIONS: 7-OHIQ is not genotoxic, for to be so
      classified it must be definitely positive in both the Ames and Williams tests;
      moreover, it is not carcinogenic, in marked contrast to IQ and NMU.

PMID- 8271279
TI  - Activity of intoplicine (RP60475), a new DNA topoisomerase I and II inhibitor,
      against human tumor colony-forming units in vitro.
AB  - BACKGROUND: Intoplicine (RP60475) is the most active analogue evaluated in the 7H
      benzo[e]-pyrido-[4,3-b]-indole series of antineoplastic compounds. It exerts its
      activity through inhibition of DNA topoisomerase I and II. PURPOSE: This study
      was planned to determine plasma concentrations of intoplicine necessary for
      optimal clinical antitumor activity, as well as to pinpoint possible responsive
      tumor types that can be included in phase II clinical studies. METHODS: Tumor
      specimens were collected from patients as part of routine clinical measures.
      Single-cell suspensions were prepared from freshly obtained solid tumor biopsy
      specimens and were exposed to intoplicine either for 1 hour or continuously. The
      sensitivity of these specimens to intoplicine was evaluated in a human tumor soft
      agar cloning assay. Response was considered positive when the colony-forming unit
      count in drug-treated samples was 50% or less than the response of control tumor
      samples treated with saline. RESULTS: With 1-hour exposure to intoplicine at
      final concentrations of 2.5 micrograms/mL and 10.0 micrograms/mL, 26% and 54% of
      the assessable specimens showed positive in vitro responses, respectively. With
      continuous exposure to intoplicine at concentrations of 0.25 micrograms/mL and
      2.5 micrograms/mL, 16% and 71% of the assessable specimens showed positive
      responses, respectively. Activity was seen against breast (71%), non-small-cell
      lung (69%), and ovarian (45%) cancer colony-forming units at a intoplicine
      concentration of 10.0 micrograms/mL after 1-hour exposure. Incomplete cross
      resistance with doxorubicin, cisplatin, fluorouracil, 4
      hydroperoxycyclophosphamide, vinblastine, and etoposide was also observed.
      CONCLUSIONS: Intoplicine appears to be active in vitro against a variety of human
      tumors, including a subgroup of tumors insensitive in vitro to standard
      antineoplastic compounds. If plasma levels of 10.0 micrograms/mL can be achieved
      in subjects in ongoing clinical trials, intoplicine could have significant
      clinical activity. IMPLICATIONS: These data indicate that further investigation
      of intoplicine is warranted.

PMID- 8271280
TI  - Dietary beta carotene and lung cancer risk in U.S. nonsmokers.
AB  - BACKGROUND: Approximately 15% of all lung cancer deaths in the United States
      (about 22,350 deaths annually) may not be directly attributable to active
      cigarette smoking. Consumption of beta carotene, which is derived almost
      exclusively from intake of fruits and vegetables, has been associated with a
      reduced risk of lung cancer in smokers. However, studies examining this
      association in nonsmokers, particularly nonsmoking men, are limited. PURPOSE: The
      purpose of this study was to examine whether dietary factors including beta
      carotene and retinol are associated with a reduced risk for lung cancer in
      nonsmoking men and women. METHODS: A population-based, matched case-control study
      of lung cancer in nonsmokers was conducted in New York State from 1982 to 1985.
      Dietary interviews were completed for 413 individually matched case-control pairs
      of subjects. To determine whether the relationship between dietary intake from
      specific food groups and lung cancer differed by type of interview, smoking
      history, sex, age, or histologic type, we examined data on the case-control pairs
      from each subgroup separately. The intake of beta carotene and retinol was
      calculated as the weighted sum of the monthly frequencies of consumption of food
      items containing these nutrients, where the weights correspond to the nutrient
      content of a typical portion of the food items. RESULTS: Consumption of greens (P
      for trend < .01), fresh fruits (P for trend < .01), and cheese (P for trend <
      .05) was associated with a significant dose-dependent reduction in risk for lung
      cancer, whereas consumption of whole milk (P for trend < .01) was associated with
      a significant dose-dependent increase in risk. Use of vitamin E supplements was
      also protective (odds ratio = 0.55; 95% confidence interval [CI] = 0.35-0.85).
      Increased consumption of the following food groups was associated with a
      reduction in risk among females: vegetables (P for trend < .025), raw fruits and
      vegetables (P for trend < .005), and dairy products (P for trend < .025). In
      males, increased consumption of raw fruits and vegetables was associated with a
      reduced risk for lung cancer (P for trend < .005). Dietary beta carotene (OR =
      0.70; 95% CI = 0.50-0.99), but not retinol (OR = 0.98; 95% CI = 0.82-1.17), was
      significantly associated with risk reduction. CONCLUSIONS: This is the largest
      study to date of dietary factors and lung cancer in nonsmokers; results suggest
      that dietary beta carotene, raw fruits and vegetables, and vitamin E supplements
      reduce the risk of lung cancer in nonsmoking men and women.

PMID- 8271281
TI  - Phase I trial of recombinant human macrophage colony-stimulating factor
      administered by continuous intravenous infusion in patients with metastatic
      cancer.
AB  - BACKGROUND: Macrophage colony-stimulating factor is a bone marrow-derived
      glycoprotein that can stimulate monocytes and macrophages, resulting in
      production of factors involved in immune response. In vitro and in vivo
      preclinical studies in animals have demonstrated that recombinant human
      macrophage colony-stimulating factor (rHuM-CSF) can have antitumor activity.
      PURPOSE: A phase I clinical trial was undertaken to evaluate the toxicity,
      pharmacokinetics, and immunologic effects of rHuM-CSF given by continuous
      intravenous infusion in patients with cancer. METHODS: Eighteen patients with
      metastatic solid tumors refractory to conventional therapy were treated with rHuM
      CSF. Twelve patients received two 14-day cycles of rHuM-CSF by continuous
      infusion, with a 2-week interval. Dose escalation levels were 50, 100, and 150
      micrograms/kg over 24 hours. Consecutive cohorts of three to six patients were
      planned at each dose level. Six patients received a modified regimen of four 7
      day periods of infusion at 100 micrograms/kg over 24 hours, with 1-week
      intervals. RESULTS: Dose-limiting toxicity was grade 4 thrombocytopenia at a dose
      of 150 micrograms/kg over 24 hours in two patients receiving the 2-week regimen.
      Platelet count nadirs and concomitant monocytosis were seen on days 7-9, but
      recovery occurred during the treatment period. Macrophage colony-stimulating
      factor serum levels were maximal on day 1 and returned to near baseline on day 7
      of infusion. Patients treated with four 7-day infusions had no treatment-limiting
      thrombocytopenia. There were no cumulative effects on platelet or monocyte counts
      or significant constitutional symptoms. Subclinical conjunctival injection was
      noted in five of 10 patients receiving screening ophthalmologic evaluation. Grade
      2 episcleritis was diagnosed in one patient, and asymptomatic perilimbal and
      retinal hemorrhages were seen in two. Two patients developed sepsis caused by the
      intravenous line, which required cessation of therapy. No objective responses
      were documented. CONCLUSION: The maximum tolerated dose of rHuM-CSF given by
      continuous intravenous infusion for 14 days was 100 micrograms/kg over 24 hours,
      with rapidly reversible, dose-limiting thrombocytopenia at 150 micrograms/kg over
      24 hours. A regimen alternating weekly cycles of infusion avoids dose-limiting
      toxicity and allows long-term treatment. IMPLICATIONS: The regimen of repeated 7
      day infusions may be useful for future studies evaluating rHuM-CSF-activated
      monocytes in therapy for long-term infectious diseases or in investigation of new
      modes of cancer therapy using rHuM-CSF in conjunction with a tumor-specific
      antibody.

PMID- 8271282
TI  - Local recurrences following mastectomy: support for the concept of tumor
      dormancy.
AB  - BACKGROUND: Local or regional recurrence of breast cancer occurs in 5%-30% of
      patients treated by Halsted radical or modified radical mastectomy. Lag time
      between treatment and recurrence varies widely, and it is not known whether the
      recurring tumor grows at a constant growth rate or at a more rapid rate after a
      period of tumor dormancy. PURPOSE: This study was undertaken to discriminate
      between the above-mentioned hypotheses, i.e., determine whether a tumor that
      recurs after mastectomy grows at a constant rate or whether it grows rapidly
      following a period of tumor dormancy. METHODS: A series of 122 patients with
      local recurrence as a first event after mastectomy for resectable breast cancer
      was evaluated. We measured the diameter of the recurring tumor (Dr) in each
      patient and calculated the diameter that the recurring tumor could have reached
      at the immediately preceding physical examination (Dpe), when no local relapse
      had yet been detected, by assuming an exponential growth during the treatment
      free interval. For patients who had a calculated diameter Dpe that was large
      enough to have been detected at the previous examination, we assumed that a tumor
      5 mm in diameter had been mistakenly missed, and the expected corresponding tumor
      diameter at the time of detection (Drc) was calculated. Finally, the minimum
      growth rate (mGR) consistent with the sequence "no detection-->recurrence of
      diameter Dr" was obtained by assuming an exponential growth from the tumor volume
      corresponding to a diameter 1 mm less than the diameter detection threshold.
      RESULTS: A wide overlap between Dr and Dpe values was observed. Seventy-two (59%)
      of 122 Dpe values were larger than the minimum Dr; 18 (15%) were even larger than
      the median Dr value. The difference between expected and observed detection rates
      was highly significant (P < .0001). Furthermore, when treatment-free intervals
      were longer than 4 years, the difference between median Dr and median Dpe values
      failed to reach statistical significance. The Drc values were significantly lower
      than the related Dr values, while the mGR values were significantly higher than
      the corresponding growth rates (paired sample t test: P < .001). CONCLUSION: This
      study provides evidence that the hypothesis of uninterrupted constant growth of
      locally recurring breast tumors should be rejected, as it implies a statistically
      significant departure from observed data. Our results suggest that a period of
      tumor dormancy followed by more rapid growth could provide an alternative and
      more reasonable description of tumor recurrence.

PMID- 8271283
TI  - Ethnic variation in the incidence, diagnosis, prognosis, and follow-up of
      children with Wilms' tumor.

PMID- 8271284
TI  - Rethinking the role of intestinal microflora in bioactivation of food-borne
      heterocyclic amine carcinogens.

PMID- 8271285
TI  - Breast cancer risk and fatty acids in the breast and abdominal adipose tissues.

PMID- 8271286
TI  - A re-examination of the cause of excess bladder cancers in chemical plant
      workers.

PMID- 8271287
TI  - Invasive cervical cancer rising in young white females.

PMID- 8271288
TI  - Tamoxifen in healthy premenopausal and postmenopausal women: different risks and
      benefits.

PMID- 8271289
TI  - Membranous glomerulonephritis and melanoma: a causal correlation?

PMID- 8271290
TI  - Re: Organochlorines and breast cancer.

PMID- 8271291
TI  - Re: Radiation-induced breast cancer.

PMID- 8271292
TI  - Effect of the synthetic retinoid fenretinide on dark adaptation and the ocular
      surface.
AB  - BACKGROUND: Fenretinide, a synthetic derivative of retinoic acid, is under study
      in clinical trials for the prevention of breast, skin basal cell, bladder, and
      oral cancer in patients at risk. Although fenretinide is well tolerated even
      after prolonged use, it does lower plasma retinol levels and thus may affect
      night vision. PURPOSE: The purpose of this study was to measure changes in dark
      adaptation resulting from fenretinide administration, to compare the measured
      results with the patient's subjective perception, to define the association with
      plasma retinol levels, to assess the reversibility of alterations in night
      vision, and to assess the effects of fenretinide on the surface of the eye.
      METHODS: The study involved 65 women who had been operated on for stage I breast
      cancer. Of the study group, 34 received 200 mg daily of fenretinide for a median
      of 32 months, while 31 control subjects did not. Dark adaptation was studied with
      the Goldmann-Weekers adaptometer and with a subjective questionnaire. Plasma
      retinol levels were measured at each test of dark adaptation. Effects of
      fenretinide on the ocular surface were evaluated through conjunctival impression
      cytology. RESULTS: Of the patients on fenretinide, eight (23.5%) showed mild and
      nine (26.5%) showed moderate alterations of measured dark adaptability, compared
      with just two controls (6.5%) with mild alterations (cumulative odds ratio =
      15.4; P = .0008). A significant inverse correlation exists between the final
      sensitivity threshold of dark-adaptometry and plasma retinol levels, with mild
      alterations arising below 16 micrograms/dL and moderate alterations below 10
      micrograms/dL. Abnormal rod function improved significantly after 7 days and
      normalized 1 month after use of fenretinide was stopped or vitamin A
      supplementation was begun, while the conventional 3-day drug suspension, or drug
      half dose, did not allow sufficient recovery. Alterations of conjunctival
      cytology were slightly higher in patients receiving fenretinide, but no clinical
      disorders of the ocular surface were observed. CONCLUSIONS: The women treated
      with 200 mg fenretinide daily showed a relatively high incidence of mild-to
      moderate alterations of dark-adaptometry as measured with the Goldmann-Weekers
      adaptometer. However, the real-life implication of the measurements is an open
      question, for the questionnaire shows that 50% of the patients with altered dark
      adaptometry were asymptomatic.

PMID- 8271293
TI  - Steady-state serum concentration of alpha tocopherol not altered by
      supplementation with oral beta carotene. The Polyp Prevention Study 1 Group.
AB  - BACKGROUND: The antioxidants beta carotene and vitamin E may play a role in
      cancer prevention. However, some studies have suggested that oral supplements of
      beta carotene may cause a decrease in serum levels of alpha tocopherol (vitamin
      E). PURPOSE: We conducted this study to determine if beta carotene supplements
      affect serum levels of vitamin E and vice versa. METHODS: Five hundred five
      patients in a clinical trial of antioxidant vitamins, used to prevent recurrences
      of colonic polyps, received either a placebo, 25 mg of beta carotene per day, 1 g
      ascorbic acid plus 400 mg alpha tocopherol per day, or all three agents combined.
      Serum levels of beta carotene and vitamin E were measured before and after 9
      months of supplementation, using high-performance liquid chromatography. RESULTS:
      Vitamin E levels changed very little among the groups receiving placebo or beta
      carotene and went up substantially and equally in the groups receiving vitamin E
      plus ascorbic acid or all three agents together. Conversely, beta carotene levels
      changed very little for the groups receiving placebo or ascorbic acid plus
      vitamin E but went up substantially and equally for the groups receiving beta
      carotene alone or all three agents. CONCLUSIONS: We conclude that oral
      supplementation with beta carotene for 9 months does not alter serum
      concentration of vitamin E and that supplementation with vitamin E plus ascorbic
      acid does not alter serum beta carotene levels.

PMID- 8271294
TI  - Anti-colony-stimulating factor-1 antibody staining in primary breast
      adenocarcinomas correlates with marked inflammatory cell infiltrates and
      prognosis.
AB  - BACKGROUND: Clinical studies have shown that a marked lymphoplasmocytic reaction
      in breast tumors is associated with poor prognosis. Such findings raise the
      possibility that an inflammatory cell reaction might be a tumor-induced response
      that tends to promote tumor growth. PURPOSE: We assessed the expression of colony
      stimulating factor-1 (CSF-1) as well as the prevalence of specific tumor
      infiltrating lymphocytes and monocytes in breast tumors. METHODS: Tissue sections
      were obtained from archival paraffin blocks from 196 breast cancer patients.
      Seventy-eight percent of the women had been treated by mastectomy and 22% by
      lumpectomy. Median age of the patients was 54 years, and median follow-up was 7.3
      years. Immunohistochemical and in situ hybridization techniques were used to
      characterize the specimens. RESULTS: Markedly high numbers of CD45RO-positive T-
      and L26-positive B-cell infiltrates were found in 13% and 17% of the tissue
      specimens, respectively. CSF-1 receptor-positive monocytes were detected in 48%
      and CD68-positive monocytes in 90% of the tumors. In turn, tumors with large
      fractions of CD68-positive monocytes also showed CSF-1 receptor-positive
      monocytes (P < .0001). CSF-1 was expressed significantly in 74% of the tumors and
      the CSF-1 receptor in more than 50% of the tumors. Tumors with high percentages
      of CSF-1 expressing cells also had marked monocyte infiltrates (P = .035). The
      presence of marked CD45RO-positive T-cell infiltrates and apparent nuclear
      staining of CSF-1 in tumor cells were associated with the more frequent
      occurrence of metastases (P = .02 and P = .04, respectively) and with poor
      survival (P = .02 and P = .03, respectively). CONCLUSIONS: Large numbers of
      CD45RO-positive (activated memory but noncytotoxic) T cells as well as a
      predominant nuclear staining pattern for CSF-1 are associated with a poor outcome
      in breast cancer patients. IMPLICATIONS: Nuclear retention of CSF-1 could reflect
      CSF-1 turnover and function in tumor cells, but new approaches are needed to
      establish the significance of these observations. Secreted CSF-1 appears to cause
      monocyte recruitment and activation, thereby modulating immune functions and
      potentially the expression of the CD45RO phenotype in T cells.

PMID- 8271295
TI  - Selective responsiveness of human breast cancer cells to indole-3-carbinol, a
      chemopreventive agent.
AB  - BACKGROUND: Indole-3-carbinol (I3C), a compound found in cabbage, broccoli, and
      brussels sprouts, inhibits the growth of mammary tumors when fed to certain
      strains of mice. The chemopreventive and antitumor effects of I3C depend on the
      species and tissue type. The mechanism of action and specific human cell types
      that respond to I3C are not known. PURPOSE: Our purpose was to study the
      mechanism of action of I3C in estrogen-responsive (MCF-7) and estrogen
      nonresponsive (MDA-MB-231) human breast cancer cell lines. METHODS: Estrogen
      responsiveness was determined by the ability of estradiol to stimulate the growth
      of breast cancer cells deprived of estrogen. The effect of I3C was measured on
      cell growth, estradiol metabolism, and level of cytochrome P-4501A1. Growth was
      measured by cell counts and soft-agar assay, estrogen metabolism was examined by
      a radiometric assay, and the level of cytochrome P-4501A1 was measured by Western
      blots with a polyclonal antibody. RESULTS: I3C inhibits the growth of estrogen
      responsive cell line MCF-7 but has little effect on estrogen-nonresponsive cell
      line MDA-MB-231. Specific C-2 hydroxylation of estrogen and induction of
      cytochrome P-4501A1 was enhanced by I3C in the MCF-7 but not in the MDA-MB-231
      cells. CONCLUSION: I3C has specific antigrowth effects in human breast cancer
      cells. The inhibitory effects of I3C may involve selective induction of estradiol
      metabolism and the related cytochrome P-450 system that may be limited to
      estrogen-sensitive cells.

PMID- 8271296
TI  - Second cancers following oral and pharyngeal cancers: role of tobacco and
      alcohol.
AB  - BACKGROUND: The exceptionally high rate of second primary cancers among patients
      with oral and pharyngeal cancers is well recognized, yet there has been limited
      epidemiologic study of risk factors for second tumors. PURPOSE: To evaluate the
      relation of smoking and alcohol consumption to the development of second cancers
      among this high-risk patient group, we conducted a nested case-control study.
      METHODS: A total of 1090 patients enrolled in a 1984-1985 population-based, case
      control study of oral cancer in four areas of the United States were followed
      through June 1989 for the occurrence of second primary cancers. Information on
      tobacco and alcohol consumption was obtained from the original interviews and was
      updated by follow-up interviews obtained for 80 case patients with second cancers
      and 189 sex-, study area-, and survival-matched cancer patients free of second
      cancers (control subjects). RESULTS: Tobacco smoking and alcohol drinking each
      contributed to risk of second cancers, with the effects of smoking more
      pronounced than those of alcohol. The odds ratios (ORs) for smoking (adjusted for
      alcohol) rose with duration and intensity of smoking and were strongest for
      tumors of the aerodigestive tract (oral cavity, pharynx, esophagus, larynx, and
      lungs), with ORs reaching 4.7 (95% confidence interval [CI] = 1.4-16) among
      smokers of 40 or more cigarettes per day for 20 or more years. Current smokers as
      of the baseline survey experienced a fourfold increased risk of a second
      aerodigestive tract cancer relative to nonsmokers and former smokers. No
      reduction in risk was associated with cessation of smoking or drinking at or
      after the index diagnosis, although the short median interval (27 months) between
      tumor diagnoses limited observation of the effects due to recent cessation. Risk
      was significantly reduced, however, 5 years after smoking cessation. Among
      drinkers, second cancer risk was greatest for beer intake, with an OR for a
      second aerodigestive tract cancer of 3.8 (95% CI = 1.2-12) for 15 or more beers
      per week. CONCLUSIONS: Oral and pharyngeal cancer patients with the highest
      intakes of tobacco and alcohol are the ones most prone to develop second primary
      cancers. IMPLICATIONS: Avoidance of tobacco smoking and alcohol drinking is the
      most desirable way not only to prevent primary oral cancers, but also to reduce
      risk of second cancers of the aerodigestive system.

PMID- 8271297
TI  - Phase IIa study of fenretinide in superficial bladder cancer, using DNA flow
      cytometry as an intermediate end point.

PMID- 8271298
TI  - Prevention of second primary tumors with isotretinoin in patients with squamous
      cell carcinoma of the head and neck: long-term follow-up.

PMID- 8271299
TI  - von Hippel-Lindau and the genetics of astrocytoma.

PMID- 8271300
TI  - Immunogenicity of the L10 hepatocarcinoma in strain-2 guinea pigs.

PMID- 8271301
TI  - Sunscreens and melanoma: implications for prevention.

PMID- 8271302
TI  - Gene therapy centers poised to proliferate.

PMID- 8271303
TI  - Successful gene therapy has researchers looking for the bystander effect.

PMID- 8271304
TI  - Study confirms high rates of adult T-cell leukemia in N.Y.C.

PMID- 8271305
TI  - AIDS epidemic cuts cancer survival in younger men.

PMID- 8271306
TI  - Researchers to comb Long Island for potential cancer factors.

PMID- 8271307
TI  - Effect of sunscreens on UV radiation-induced enhancement of melanoma growth in
      mice.
AB  - BACKGROUND: Epidemiologic evidence suggests that exposure to UV radiation plays a
      significant role in the development of melanoma skin cancers. As early surgical
      removal of the melanoma is the only effective therapy, current strategies for
      reducing mortality from melanoma focus on prevention of the disease. Chemical
      sunscreens protect mice from development of skin cancers that resemble sunlight
      induced human squamous cell cancers, but there appears to be a complex
      relationship between UV radiation exposure and development of melanoma. PURPOSE:
      We asked whether common sunscreens would protect mice against UV radiation
      induced enhancement of melanoma incidence. METHODS: C3H mice were exposed to 4.8
      kJ/m2 UVB from FS40 sunlamps twice a week for 3 weeks. Sunscreens containing 7.5%
      2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-aminobenzoate, 6%
      benzophenone-3, or the oil-in-water vehicle alone were applied to the ears and
      tails of the mice 20 minutes before irradiation. At various times during and
      after exposure, we determined UV radiation-induced inflammation by measuring ear
      swelling. We also examined the ears histologically for UV radiation-induced
      alterations. One day after the final irradiation, 2.5 x 10(4) syngeneic K1735
      melanoma cells were injected into the external ears. Mice were examined weekly
      for tumor growth for 5-8 weeks after tumor cell injection. Control mice were
      treated in the identical way except for exposure to UV radiation. RESULTS: The
      incidence of melanomas was significantly higher in the UV-irradiated mice. All
      three sunscreens protected against UV radiation-induced ear swelling and clearly
      diminished histopathologic alterations, including sunburn cell formation,
      epidermal hyperplasia, and mononuclear cell infiltrate in the dermis. However,
      the sunscreens failed to protect against UV radiation-induced increase in
      melanoma incidence. The sunscreens or vehicle alone did not significantly alter
      tumor growth. CONCLUSIONS: Protection against sunburn does not necessarily imply
      protection against other possible UV radiation effects, such as enhanced melanoma
      growth. IMPLICATIONS: Sunscreen protection against UV radiation-induced
      inflammation may encourage prolonged exposure to UV radiation and thus may
      actually increase the risk of melanoma development. These findings suggest that
      further research on the ability of sunscreens to prevent melanoma is urgently
      needed.

PMID- 8271308
TI  - Induction of c-fos by excitatory amino acids in developing chick retina is
      affected by changes in cellular interactions.
AB  - Cell contact is important for normal maturation of chicken retinal Muller cells.
      In order to gain a better understanding as to how this occurs, we examined the
      ability of retinal cells with altered cell contacts to respond to an
      environmental stimulus. The response of Muller cells cultured under conditions
      which alter cell contacts was measured by activating intracellular signaling
      systems leading to induction of the early-inducible gene c-fos. Chicken retinal
      cells were cultured as explants, reaggregates, and monolayers and exposed to
      extracellular stimuli in the form of the excitatory amino acids D,L-alpha
      aminoadipic acid (AAA) and N-methyl-D,L-aspartic acid (NMDA). Each culture was
      exposed to 1.25 mM AAA, 2.5 mM AAA, 50 microM NMDA, or 100 microM NMDA. Toxicity
      was assessed histologically and by immunocytochemical labeling of Muller cells
      after 2 days of exposure. Activation of c-fos was determined by Western blot
      analysis for Fos protein after 30, 60, and 120 minutes of exposure. Exposure to
      AAA led to a loss of Muller cells in explant and reaggregate cultures; however,
      Muller cells in monolayer culture were not susceptible to AAA at either dose.
      NMDA was toxic to a specific population of neurons under all three culture
      conditions. Fos protein expression paralleled the histologic findings. Fos
      protein was significantly elevated after exposure to either dose of AAA in
      explant and reaggregate cultures but not in monolayer cultures.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8271309
TI  - Retinal morphology and visual pigment levels in 6- and 12-month-old rhesus
      monkeys fed a taurine-free human infant formula.
AB  - Rhesus monkey infants were raised from birth until 6 or 12 months of age on a
      taurine-free soy protein-based human infant formula or on the same formula
      supplemented with taurine. An additional group received taurine-free formula
      until 6 months and then the supplemented diet from 6 until 12 months. The
      densities of rod and cone visual pigments were measured by fundus reflectometry
      at 6 and 12 months, and retinal morphology was then examined by light and
      electron microscopy. The densities of rhodopsin, measured in the near periphery
      after a white bleach, and of cone pigment, measured in the macula after a red
      bleach, were significantly reduced in the taurine-deprived monkeys at 6 months
      but not at 12 months. The retinas of 6-month-old taurine-deprived infants showed
      degenerative morphological changes in photoreceptors, particularly in cones in
      the foveal region, which were somewhat less severe than those seen in a previous
      study at 3 months of age. The prevalence and degree of these abnormalities
      continued to decrease with age in taurine-deprived animals, but changes persisted
      in some animals at 12 months. Recovery was more complete in monkeys reversed to
      the supplemented diet from 6 to 12 months. Thus, monkey infants are dependent on
      dietary taurine to maintain normal retinal structure until at least 6 months of
      age; the effects of taurine deprivation regress spontaneously but incompletely by
      12 months.

PMID- 8271310
TI  - Characterization of the neuroimmune protein F5: localization to the dendrites and
      perikarya of mature neurons and the basal aspect of choroid plexus epithelial
      cells.
AB  - F5 was identified originally as an interleukin-2-regulated gene in L2 cells, a
      murine helper T-lymphocyte clone. In adult mouse, F5 mRNA was expressed at a
      modest level in lymphoid tissues, at a high level in mature neurons in the
      nervous system, but not in other tissues. Although the F5 sequence is highly
      conserved over evolution, the function of the F5 protein is unknown. In the
      present studies, the putative F5 protein-coding region was translated in vitro
      using a reticulocyte lysate system and in Escherichia coli, yielding a protein
      with the predicted molecular weight of 42 kDa. Polyclonal rabbit anti-F5 antibody
      was generated against a synthetic peptide corresponding to the C-terminus of the
      F5 protein. This antibody specifically recognized recombinant F5 protein. Western
      blot studies demonstrated a strongly-reactive 42-kDa band and a faint 39-kDa band
      in extracts of adult mouse brain regions, the levels of which paralleled F5 mRNA
      expression. Immunoperoxidase studies of adult mouse brain demonstrated F5
      immunoreactivity in neuronal perikarya and dendrites but not axons. Neurons
      expressing the highest levels of F5 protein corresponded to those with the
      highest levels of F5 mRNA. Choroid plexus epithelial cells also exhibited strong
      reactivity localized to their basal aspect. These observations suggest that the
      F5 protein, expression of which appears to be regulated predominantly at the RNA
      level, may be involved in the maintenance of the functional or anatomic polarity
      of neurons and choroid plexus epithelial cells.

PMID- 8271311
TI  - cDNA cloning and expression of stress-inducible rat hsp70 in normal and injured
      rat brain.
AB  - A reverse transcriptase-polymerase chain reaction (RT-PCR) product obtained from
      ischemic rat brain RNA was used to screen a rat ischemic forebrain cDNA library
      for a cDNA clone containing the entire open reading frame for the inducible
      hsp70. The coding sequence for the rat hsp70 cDNA demonstrated significant
      similarities with the human hsp70 of Hunt and Morimoto (Proc Natl Acad Sci
      82:6455-6459, 1985) and the mouse hsp70 of Hunt and Calderwood (Gene 87:199-204,
      1990). The rat inducible hsp70 and constitutive hsc73 sequences are distinct.
      There was a low level of hsp70 mRNA expression in normal rat brain as in found in
      other tissues. hsp70 mRNA was markedly induced in rat brain 8 hours following
      global ischemia and kainic acid-induced seizures. Northern blots showed a
      approximately 2.9kb hsp70 mRNA band from control, kainic acid, and ischemic
      brains. RT-PCR confirmed the presence of hsp70 mRNA in normal rat brain. Since
      there are at least five human and six mouse inducible hsp70 genes known, many
      other rat hsp70 genes probably exist that could function in different cells or
      organelles or be induced under different circumstances.

PMID- 8271312
TI  - Outstations of the Golgi complex are present in the processes of cultured rat
      oligodendrocytes.
AB  - Primary cultures of rat oligodendrocytes were incubated with a fluorescent
      sphingolipid precursor, 6-[N-(7-nitrobenz-2-oxa-1,3-diazol-4
      yl)amino]hexanoylceramide+ ++ (C6-NBD-ceramide). This compound is known to stain
      the Golgi complex specifically. Within 30 min of incubation at 37 degrees C most
      of the C6-NBD-ceramide was incorporated into the perinuclear Golgi system, as
      revealed by conventional and confocal laser fluorescence microscopy.
      Interestingly, C6-NBD-ceramide was found to accumulate also in smaller, oval
      shaped structures in many of the processes, at distances up to 30 microns from
      the nucleus. This implies the possibility that these structures are Golgi (
      derived) complexes. Indeed, after incubation of oligodendrocytes with C6-NBD
      ceramide and rhodamine-labeled transferrin both fluorescent labels colocalized in
      the Golgi system of the cell body as well as in the structures in the processes.
      Additional support for the Golgi character of these structures was obtained by
      transmission electron microscopy. Particularly in oligodendrocytes cocultured
      with neurons, many Golgi structures were present all over the processes. The
      results lead us to conclude that, in the oligodendrocyte, the Golgi complex does
      not only reside in the perikaryon, but also in the processes. One can speculate
      that a polarized biosynthetic activity, involving the presence of the Golgi near
      the site of myelin synthesis, may be advantageous to the oligodendrocyte for
      assembly and/or repair of the myelin membrane at the distal end of the processes.

PMID- 8271313
TI  - AMPA-selective glutamate receptor subunits in astroglial cultures.
AB  - We analysed AMPA ionotropic receptor subunits at the mRNA level (GluR-1 to -4)
      and at the protein level (GluR-1 and GluR-2/3/4c) in "primary astroglial
      cultures" (non-neuronal cell cultures highly enriched in glial fibrillary acidic
      protein [GFAP] positive cells) prepared from newborn rat cerebral hemispheres,
      cerebral cortex, hippocampus, and striatum and in "brain non-neuronal cell
      cultures" (low percentage of GFAP positive cells) prepared from cerebellum,
      brainstem, mesencephalon, and hypothalamus. For comparison, we also determined
      AMPA subunit mRNA and protein levels in different brain regions. By Northern blot
      analysis mRNAs for the AMPA receptor subunits (GluR-1,-2,-3,-4) were detected in
      primary rat cerebral hemispheres astroglial cultures. Immunoblotting analysis
      with anti-GluR-1 and anti-GluR-2/3/4c polyclonal antibodies confirmed the
      presence of low level of immunoreactive proteins of the same size of those
      identified in vivo as GluR subunits. Expression of GluR genes varied depending on
      the brain area used as starting material for the preparation of the cultures:
      GluR-1, -2, and -3 were mainly expressed in cortical cultures, while GluR-4
      expression predominated in brainstem derived cultures. Interestingly this pattern
      of expression correlates with that observed in the intact brain, where high
      levels of GluR-4 mRNA and low levels of the other GluR subunits were found in the
      brainstem. In conclusion our results confirm the existence of glutamate
      ionotropic receptors of the AMPA type in primary astroglial cultures and suggest
      that GluR-4 is the main AMPA receptor subunit expressed in non-neuronal cells of
      the central nervous system.

PMID- 8271314
TI  - Expression of mRNA for neurotrophic factors and their receptors in the rat dorsal
      root ganglion and sciatic nerve following nerve injury.
AB  - The adult rat dorsal root ganglion (DRG) produces mRNA for the neurotrophic
      factors nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)
      and contains large populations of neurons responsive to these factors. We report
      that following a focal crush injury of the sciatic nerve, NGF mRNA expression
      increases threefold and BDNF mRNA two-fold, in the ipsilateral L4 and L5 DRGs.
      The mRNAs encoding the cognate neurotrophin receptors, p75NGFR, trkA, and trkB
      were expressed in the DRG throughout the post-injury time course, suggesting that
      DRG neurons remain responsive to both NGF and BDNF. p75NGFR mRNA levels became
      transiently depressed in the DRG during the first several days after the lesion
      but returned to normal within 1 week. trkB mRNA was expressed in the normal
      sciatic nerve and levels were not altered by nerve crush. RNase protection assays
      detected both full-length and truncated trkB transcripts in the DRG, but only
      truncated trkB mRNA, lacking the tyrosine kinase domain, was detected in the
      sciatic nerve. Likewise, trkA transcripts were not detected by RNase protection
      in normal sciatic nerve or in a segment of nerve distal to the crush site. These
      results are consistent with a model in which regenerating sensory neurons are
      supported by neurotrophic factors synthesized within the DRG.

PMID- 8271315
TI  - Cellular reaction to an acute demyelinating/remyelinating lesion of the rat brain
      stem: localisation of GD3 ganglioside immunoreactivity.
AB  - We describe a simple and reproducible acute demyelinating lesion of the rat brain
      stem induced by injection of ethidium bromide into the cisterna magna of young
      adult rats. Using immunofluorescence with a panel of antibodies to cell-specific
      antigens we have studied the changes in cell populations that occur at various
      stages during lesion progression and repair. In particular we localized the
      expression of ganglioside GD3 immunoreactivity, a marker for oligodendroglial
      progenitors in developing brain. Both astroglia (GFAP+) and oligodendroglia
      (CNP+) were destroyed during the early response to the ethidium bromide although
      axons were spared. Splitting of myelin lamellae occurred as early as 4 days post
      injection (DPI), with extensive demyelination of the inferior cerebellar peduncle
      following by 6 DPI. Large numbers of ED1+ and OX-42+ macrophages were present in
      the lesion site at this stage. Astrogliosis occurred around the perimeter of the
      lesions. Two populations of GD3+ cells appeared within and around the lesion
      sites during the demyelination. One population was identified by the phenotype
      GD3+ ED1+ and thus probably belonged to the macrophage/microglial lineage. In
      these cells both antigens appeared cytoplasmic. The second population of GD3+
      cells exhibited cell membrane GD3 immunoreactivity but did not express the ED1
      antigen. These cells are suggested to be oligodendroglial progenitors generated
      in response to the demyelination. No such cells were seen in control tissue. GD3+
      cells were present within the lesion sites from 6 DPI until 10-12 DPI. Following
      the clearance of myelin debris from the lesions, remyelination was a relatively
      rapid event with thin MBP+ myelin sheaths first seen at 11-12 DPI. Remyelination,
      which was extensive by 25 DPI, was predominantly oligodendroglial in origin
      (MBP+P0- myelin) with only small pockets of peripheral myelin (MBP+P0+ myelin)
      observed. The present study, in addition to identifying putative glial
      progenitors within a demyelinated lesion, also demonstrates the difficulties in
      unambiguously identifying such cells in the normal and damaged adult CNS.

PMID- 8271316
TI  - Glycerophosphorylcholine phosphocholine phosphodiesterase activity during the
      differentiation of glial progenitor cells.
AB  - O-2A progenitor cells were grown in medium containing either 1% or 10% fetal calf
      serum (FCS) for 4 weeks. The cells in 1% FCS were 75% oligodendrocytes by 3 weeks
      in culture. The cell population was so overgrown with astrocytes in the 10%
      medium that an accurate estimate of cell number could not be made. The activities
      of glycerophosphorylcholine phosphocholine phosphodiesterase (GPC-PC-PdE), p
      nitrophenylphosphorylcholine phosphodiesterase (pNPPC-PC-PdE), and ceramide UDP
      galactose galactosyl transferase (CGalT) were barely detectable in the cells
      grown in 10% FCS. The activities of these 3 enzymes were low in the cells grown
      in 1% FCS for the first 2 weeks and then all 3 increased manyfold. These
      observations reinforce the evidence previously accrued showing that these two
      phosphodiesterase activities (GPC-PC-PdE and pNPPC-PC-PdE) are markers of
      oligodendroglial cells as well as myelin. In contrast, glycerophosphorylcholine
      choline phosphodiesterase (GPC-C-PdE) activities were present in cells grown in
      both 1% and 10% FCS.

PMID- 8271317
TI  - Gangliosides stimulate synthesis of prostaglandin E2 and prostacyclin in fetal
      rat brain hemispheres after episodes of global intrauterine ischemia.
AB  - The ability of brain preparations from 20-day-old rat fetuses to synthesize
      prostanoids in vitro before and after interruption of the maternal-fetal blood
      flow was examined using a radioimmunoassay technique. Synthesis of thromboxane B2
      (TxB; the stable thromboxane A2 metabolite) decreased with increasing restriction
      time; conversely, it was elevated with reperfusion. Synthesis of 6-keto
      prostaglandin F1 alpha (PGF; the stable prostacyclin metabolite) and
      prostaglandin E2 (PGE) prostanoids remained unchanged after 20 min restriction
      and through a 2 hr reperfusion period. Intraperitoneal administration of GM1 (45
      mg/kg) into the pregnant rat, 3 hr before restriction, stimulated synthesis of
      PGE and reduced synthesis of TxB. A prostanoid vasoactive index (PVI), which
      reflects the relative proportion of the three prostanoids synthesized and asserts
      the vasoactive potential of the brain tissue, was established. A rise in this
      value was attained after intrafetal administration into the peritoneal cavity of
      either GM1, GM3, or isopropyl-GM1 (AGF44) gangliosides, each given at 40
      micrograms dose in 5 microliters volume, and N-dichloroacetyl-sphingosine
      (LIGA20; 15 micrograms/5 microliters) ganglioside analog, 1 hr before
      restriction. The effect was primarily due to an increase in the capacity of fetal
      brain tissue to synthesize PGE and, to a lesser extent PGF, vasodilating
      prostanoids. The N-methyl-D-aspartate (NMDA) receptor-blocker MK801 (6.6
      micrograms/2 microliters) and the platelet activating factor (PAF) receptor
      antagonist BN52021 (0.1 mumol/2 microliters), given by the same route,
      effectively raised by 60-80% the vasodilating potential of the brain tissue
      following ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271318
TI  - Temporal and spatial distribution of heat shock mRNA and protein (hsp70) in the
      rabbit cerebellum in response to hyperthermia.
AB  - We have previously investigated the expression of hsp70 genes in the hyperthermic
      rabbit brain at the mRNA level by Northern blot and in situ hybridization
      procedures. Our studies have now been extended to the protein level utilizing
      Western blot and immunocytochemistry. Using an antibody which is specific to
      inducible hsp70, a prominent induction of hsp70 protein in glial cells of
      hyperthermic animals was noted. In particular, Bergmann glial cells in the
      cerebellum are strongly immunoreactive while adjacent Purkinje neurons are
      immunonegative. Extension of our in situ hybridization studies to a time course
      analysis revealed that the initial glial induction events were followed by a
      delayed accumulation of inducible hsp70 mRNA in Purkinje neurons at 10 hr post
      heat shock. In control animals, high levels of constitutively expressed hsc70
      mRNA and protein were observed in Purkinje neurons. Similar hsc70 and hsp70 mRNA
      observations were also made in neurons of the deep cerebellar nuclei and in motor
      neurons of the spinal cord. Our results suggest that these neuronal cell types
      accumulate hsp70 mRNA in response to hyperthermic treatment; however, the
      response is delayed when compared to the rapid response seen in glial cells. The
      high constitutive levels of hsc70 in certain neuronal cell types may play a role
      in the initial dampening of the hsp70 induction response in these cells.

PMID- 8271319
TI  - Lipocortin 1 immunoreactivity identifies microglia in adult rat brain.
AB  - Immunohistochemical localization of two Ca(++)-binding proteins, Lipocortin 1
      (LC1) and S100-beta, demonstrates two distinct classes of primitive glia in the
      floor plate of rat embryos. With proper fixation (formalin-lysine-periodate
      acetic acid), dendritic glia in the CNS of adult rats also apparently stain for
      either LC1 or S100-beta in the ratio of 1:3. In order to further distinguish and
      identify these two glial classes, we have examined their population density,
      topography, and responses to localized neuron death. Neurons of the ipsilateral
      thalamus undergo apoptosis following cortical ablation; the contralateral
      thalamus serves as control. By eight days post-lesion, the number of LC1 cells in
      the ipsilateral thalamus has increased > 4-fold, the increase comprising
      primarily activated phagocytes adjacent to degenerating neurons. The S100-beta
      glia in the same region are virtual- ly indistinguishable from control; but
      background staining (apparently representing extra-cellular S100-beta) is
      increased. Thus, the responses of dendritic LC1 glia resemble these previously
      described for microglia and are quite different from the astrocytes identified by
      S100-beta immunoreactivity. Both dendritic and activated forms of LC1 glia stain
      with the microglial marker, Griffonia simplicifolia iso-lectin B4. However,
      before the correspondence of LC1 glia and microglia can be confirmed, two
      anomalies require resolution: (1) the LC1 glia are greater in number and more
      evenly distributed than microglia marked with other methods; (2) the dendritic
      LC1 glia apparently are progeny of primitive glia that form the midline raphe of
      the embryonic floor plate. The participation of LC1 glia in the removal of CNS
      debris supports the hypothesis that LC1 plays anti-inflammatory and/or
      immunosuppressive roles in phagocytes.

PMID- 8271320
TI  - The role of smoking in periodontal diseases: a review of the literature.

PMID- 8271321
TI  - Polylactic acid used as a barrier membrane to enhance healing in human
      periodontal defects: a clinical study.

PMID- 8271322
TI  - Determination of thiocyanate anion as an organic derivative by gas
      chromatography.
AB  - A simple and sensitive gas chromatographic method has been established for the
      determination of biologically active thiocyanate anion as pentafluorobenzyl
      thiocyanate. The method is based on the partition of an ion-pair from the
      thiocyanate anion and a complex crypstand to a benzene layer for derivatization
      with pentafluorobenzyl bromide. The resulting derivative was analyzed by gas
      chromatography with electron capture detection. The quantitation range for
      thiocyanate anion was over 0.086 and 3.45 nmol. The detection limit of
      thiocyanate in 0.2 ml sample is about 34 pmol. The effects of several parameters
      such as base or acid, reaction time and the amount of pentafluorobenzyl bromide
      were evaluated for the optimization of partition and derivatization of
      thiocyanate anion. Application of the method to the analysis of thiocyanate in
      waste water and human saliva proved to be feasible.

PMID- 8271323
TI  - TV watching, soap opera and happiness.
AB  - One hundred and fourteen subjects reported the amount of time they spent watching
      television in general, and soap opera in particular. They also completed scales
      measuring happiness and other personality variables, such as extraversion and
      cooperativeness. In the multiple regression analysis, having controlled for the
      demographic variables, watching TV was related to unhappiness, whereas watching
      soap opera was related to happiness. Discriminant analysis showed that females,
      higher happiness and extraversion distinguished regular soap watchers (who
      nevertheless watched little TV in general) from irregular soap watchers (who
      nevertheless watched a lot of TV in general).

PMID- 8271324
TI  - An in-service education program as a means to improve nurses' knowledge and
      attitude about AIDS and to increase their willingness to care for AIDS patients.
AB  - This study evaluates changes in nurses' knowledge and attitudes about AIDS and
      changes in their willingness to care for AIDS patients following a 2 hour
      educational program. The nursing staff of Kaohsiung Medical College Hospital was
      divided into two groups: an experimental group (n = 280) and a control group (n =
      119). Scores were obtained from a pre-test and from a post-test. The
      questionnaire that was given to both groups. The results were analyzed by 2-way
      ANOVA with repeated measures. The experimental group's overall pre-test score on
      their knowledge of AIDS was 25.9 +/- 4.5 (66.4% of the maximal score of 39) and
      the post-test score showed an improvement to 28.7 +/- 4.2 (73.6% of the maximal
      score). The difference between the pre-test and post-test scores of the
      experimental group was statistically significant (P < 0.01). The difference in
      the post-test scores between the experimental group and the control group (26.0
      +/- 4.0) was also statistically significant (P < 0.01). Pertaining to attitudes
      towards AIDS, the experimental group had a pre-test score of 47.2 +/- 5.2 and a
      post-test score of 47.3 +/- 5.5, and there was neither a significant difference
      between the pre-test score and the post-test score of the experimental group nor
      in the post-test scores between the experimental group and the control group
      (47.6 +/- 4.3). The post-test score of willingness to care for AIDS patients was
      slightly higher than the pre-test score in both groups, but the difference was
      not significant. Nurses who originally were willing to care for AIDS patients had
      a more positive attitude toward AIDS than did nurses who had originally refused
      to care for AIDS patients in the pre-test and post-test (p < 0.01). In
      conclusion, the in-service education apparently enhanced the knowledge of AIDS,
      however, no statistical difference was established for changes in nurses'
      attitudes or in their willingness to care for AIDS patients. In order to provide
      better nursing care, we believe, AIDS knowledge needs to be further promoted.

PMID- 8271325
TI  - Effect of ionic contrast medium on plasma atrial natriuretic peptide.
AB  - To evaluate the effect of ionic contrast medium on plasma atrial natriuretic
      peptide (ANP) and its contributing factors, we measured plasma ANP, serum
      osmolality, pulmonary capillary wedge pressure (PCWP), femoral artery systolic
      pressure (FASP), and heart rate before and after left ventriculography with
      Rayvist in 13 patients suspected of coronary artery disease. The control values
      of plasma ANP, serum osmolality, and PCWP were 20.3 +/- 5.1 pg/ml, 293.5 +/- 1.5
      mosm/kg, 6.6 +/- 0.8 mm Hg, respectively. Rayvist produced a significant increase
      in plasma ANP, serum osmolality, and PCWP at 1 minute (26.0 +/- 6.3 pg/ml, p <
      0.05; 300.7 +/- 1.9 mosm/Kg, p < 0.001; 10.7 +/- 1.3 mm Hg, p < 0.001) and 5
      minutes (27.3 +/- 6.3 pg/ml, p < 0.01; 296.8 +/- 1.9 mosm/Kg, p < 0.001; 10.4 +/-
      1.7 mm Hg, p < 0.01) post left ventriculography. The FASP decreased significantly
      at 1 minute, followed by an insignificant increase at 5 minutes. The heart rate
      increased significantly at 1 minute but no significant change was noted at 5
      minutes. We conclude that plasma ANP increases significantly after left
      ventriculography with Rayvist and its response may be related to left ventricular
      filling pressure and serum osmolality, but not to FASP or heart rate.

PMID- 8271326
TI  - Ankle arthrodesis.
AB  - As a fused ankle provides a painless ankle joint with limited functional
      disability, ankle arthrodesis is still the treatment of choice for most disabling
      ankle arthritis. From January 1987 to December 1990, 45 cases of ankle
      arthrodesis were performed, including 27 male and 18 female patients, aged from
      18 to 70 years with an average of 41.9 years. The causes leading to arthrodesis
      included 19 cases of post-traumatic arthritis, 3 rheumatoid arthritis, 7
      osteoarthritis, 9 ankle infections (4 pyogenic and 5 tuberculosis), 4 ankle
      deformities, 2 avascular necrosis of the talus and 1 cases of Charcot joint. The
      methods included modified Blair's ankle arthrodesis (34 cases), compression
      arthrodesis (7 cases) either by Hoffman external fixation or triangular
      compression device, and intra articular arthrodesis by staple fixation (4 cases).
      The follow up period ranged from 17 Ms to 52 Ms with an average of 28.6 Ms. There
      were 2 cases who ultimately required amputation due to uncontrollable infection,
      and 2 cases of nonunion and one of them received refusion. There were 11 cases of
      delayed union (union time more than 6 Ms). The average union time was 5.6 Ms,
      ranging from 2 Ms to 10 Ms. Excluding the cases of amputation and nonunion, all
      patients had improvement in the ankle functional scale evaluation and 85.3% of
      the patients were satisfied with their present condition. The modified Blair's
      method of ankle arthrodesis has proven to be an effective method for treating
      ankle arthritis no matter what the cause. However, for cases of infection,
      compression arthrodesis with an external fixational device is superior.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8271327
TI  - Experience in the morbidity associated with double-J catheter indwelling and its
      management.
AB  - Placement of internal ureteral stents for internal urinary diversion and
      prevention of urological complications has been well established. However,
      indwelling stents have occasionally been associated with patient morbidity and
      intolerance. A total of 255 patients while the internal ureteral stent had been
      used were analyzed. The symptoms including urinary frequency (42.0%), hematuria
      (41.6%) and suprapubic pain (20.4%), loin pain (17.3%) and micturition pain
      (16.9%) accounted for the major complaints of the stent indwelling patients. The
      major complications, i.e. stent migration, heavy encrustation, pyelonephritis,
      fragmentation, intolerance and penetration of collecting structure, were
      occasionally observed. These complications increase secondary morbidity in
      patients. The double-J stents should be used carefully with regard to the
      prevention and treatment of untoward conditions as early as possible.

PMID- 8271328
TI  - [Surgical management of blunt abdominal trauma].
AB  - From 1986 to 1990, 175 patients with blunt abdominal trauma were hospitalized and
      operated on in Kuang Tien General Hospital. Included were 140 males and 35
      females with a mean age of 33 years (range: 2 to 82). The mean duration of the
      follow-up was 42 months. We classified the severity of the injured organs with
      the organ injury scale which was published by the Organ Injury Scaling (O.I.S.)
      Committee of the American Association for the Surgery of Trauma (A. A. S. T.) in
      1989 and 1990. Among the patients, 12 cases were treated with splenorrhaphy.
      Eighty-two cases underwent splenectomy. Four cases underwent partial resection of
      the liver. Three cases required repair of the inferior vena cava. Seventeen cases
      were treated with partial resection of the small intestine and anastomosis. Seven
      cases underwent colostomy. Three cases were treated with distal pancreatectomy.
      Nineteen cases underwent nephrectomy. One case was treated with partial
      nephrectomy. The mortality rate was 6.3%, and the morbidity rate 20.6%. The most
      frequent postoperative complications related to blunt abdominal trauma in the
      patients who survived the initial operation were wound infection (8.0%), small
      bowel obstruction (4.0%), pulmonary infection (2.3%), intra-abdominal abscesses
      (2.3%), pancreatitis (1.7%), pancreatic fistula (1.7%), and pseudocyst (0.6%).

PMID- 8271329
TI  - [Relapsing polychondritis: report of a case and review of the literature].
AB  - Relapsing polychondritis (RP) is a rare disease of unknown etiology,
      characterized by episodic and progressive chondritis, ocular and audiovestibular
      involvement, and occasional cardiovascular abnormalities. The inflammation
      typically involves the cartilage of the ears, nose, trachea, larynx, ribs,
      joints, and Eustachian tubes. The major clinical features include auricular
      chondritis, arthritis, nasal chondritis, ocular inflammation, chondritis of the
      respiratory tract, audiovestibular damage, and cardiovascular disorders. RP
      occurs predominantly in Caucasians and is uncommon in Oriental patients. Two
      cases of RP have previously been reported in Taiwan. We report one Taiwanese
      patient who was diagnosed with RP according to the criteria proposed by Damiani
      and Levine. The patient has bilateral auricular chondritis, episcleritis, and
      uveitis. Successful treatment was accomplished with systemic corticosteroid and
      topical corticosteroid eye drops. At an outpatient visit one year and ten months
      after discharge, there was no evidence of recurrence.

PMID- 8271330
TI  - Dengue and dengue haemorrhagic fever.

PMID- 8271331
TI  - Street children.

PMID- 8271332
TI  - The usefulness of weight gain in predicting pregnancy complications.
AB  - The usefulness of recently constructed centile charts for weight gain during
      pregnancy was studied. The association of weight gain in pregnancy with pregnancy
      complications was investigated. The incidence of pre-eclampsia and small for
      gestational age babies both had a significant relationship with weight gain. Use
      of the charts to screen for pregnancy complications on a selected population had
      both a sensitivity and specificity of about 50 per cent. The positive and
      negative predictive values of the charts ranged from 49 to 53 per cent. The
      question arises as to whether the routine recording of maternal weight at each
      antenatal visit is necessary.

PMID- 8271333
TI  - Hypoglycaemia: a common problem among uncomplicated newborn infants in Nepal.
AB  - Among a cross-sectional sample (stratified by weight and age after birth) of 226
      uncomplicated term newborns from the delivery and postnatal wards of a busy
      government maternity hospital in Kathmandu, the period prevalence of
      hypoglycaemia (corrected blood glucose of < 2.6 mmol/l) during the first 50 hours
      after birth was 38 per cent. (This compares with a reported prevalence rate of 12
      per cent from studies of uncomplicated term newborns in the UK.) Hypothermia,
      young maternal age, low birth weight and early sampling after birth were
      independent risk factors for hypoglycaemia. Of 31 infants studied longitudinally
      during the same period, 27 (87 per cent) had at least one blood glucose
      measurement of < 2.6 mmol/l and 25 (81 per cent) a rectal temperature of < 35.5
      degrees C. Fourteen infants (44 per cent) had three or more episodes of
      hypoglycaemia and seven infants (22 per cent) had three or more episodes of
      hypothermia. Hypoglycaemia is a common, preventable and neglected problem in many
      maternity hospitals in developing countries. Simple low-cost measures to reduce
      the incidence of hypoglycaemia may have a major impact on early infant mortality
      and neurodevelopmental sequelae of perinatal origin.

PMID- 8271334
TI  - Quantitation of salivary, urinary and faecal sIgA in children living in different
      conditions of antigenic exposure.
AB  - A sandwich-type ELISA was developed to quantify salivary, urinary and faecal
      secretory IgA (sIgA). The assay is based on binding of sIgA to microplates coated
      with anti-SC antibodies and reaction with peroxidase-labelled anti-IgA. The
      sensitivity of the technique was approximately 5 micrograms/L. Children, 1-6
      years old (n = 142), were divided into two groups. Group 1 (n = 80) was composed
      of children living in a place with presumably low antigenic exposure conditions.
      Group 2 (n = 62) was composed of well-nourished (2A, n = 53) and malnourished
      children (2B, n = 9) living in a Sao Paulo slum with presumably high antigenic
      exposure. The subgroup 2A had salivary levels higher than group 1 and the ranges
      were similar to those found in the literature for older children and adults. The
      same subgroup presented a high incidence of undetectable faecal sIgA; their
      levels of urinary sIgA did not differ from group 1. The subgroup 2B did not have
      levels of salivary, urinary and faecal sIgA different from subgroup 2A. Our
      results suggest that environmental factors influence the ontogenesis of sIgA
      system.

PMID- 8271335
TI  - Evaluation of CSF variables as a diagnostic test for bacterial meningitis.
AB  - Specific aetiological diagnosis of bacterial meningitis (BM) in developing
      countries is often difficult. Frequently, differentiating BM from viral and TB
      meningitis is not easy. A study was carried out with the easily and quickly
      performed CSF morphological and biochemical changes as a diagnostic test against
      the gold standard of CSF culture and/or the latex agglutination test (LAT).
      Children between 2 months and 11 years of age, suspected to have acute
      meningitis, were prospectively recruited. CSF cell count and morphology, Gram
      stain, culture, and protein and sugar estimations were carried out as per
      standard procedures. The laboratory personnel were blind to the clinical details
      and the findings of each other. Diagnosis based on gold standard was possible in
      55 out of 114 cases. With CSF polymorphs > 60 per cent and sugar < 50 per cent of
      blood level as constants, various levels of total cells and protein were
      considered for their diagnostic properties. The protein level was not useful. We
      found the best cut-off level of cell count for diagnosis of BM to be 300/mm3,
      based on the receiver operating characteristics curve, the point of maximum
      accuracy. These findings were validated by comparing the clinical features, CSF
      changes and outcome characteristics of non-confirmed cases with the above
      criteria with the confirmed cases; these were found to be the same except for
      age.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271336
TI  - ARI control programme: results in hospitalized children.
AB  - One hundred cases of pneumonia with chest indrawing were treated according to the
      treatment protocol of the ARI control programme. The majority of children were >
      2 months old (85 per cent) with male predominance (61 per cent). All cases with
      severe pneumonia survived. A mortality rate of 7.7 per cent was seen in cases of
      very severe pneumonia. Three children in the severe pneumonia group deteriorated
      on benzyl penicillin to very severe pneumonia but subsequently improved on
      chloramphenicol. Six patients were treated as cases of Staphylococcal pneumonia
      and one of them died. Thirteen children (21.3 per cent) in the severe pneumonia
      group required oxygen for breathing rates > 70 per minute. Seventy-four per cent
      in the very severe pneumonia group required administration of IV fluids. Blood
      counts did not prove to be of help in differentiating the children at risk of
      dying. There was no significant difference in roentgenographic findings in the
      two groups. Congestive cardiac failure was the most common complication, seen in
      33.3 per cent of cases of the very severe pneumonia group. The duration of stay
      was significantly less in cases of severe pneumonia (4.21 +/- 1.59 days) as
      compared to very severe pneumonia (9.35 +/- 2.39 days). The data from this study
      suggest that the treatment protocol for the ARI control programme for
      hospitalized children is reasonably effective and can be implemented in small
      hospitals.

PMID- 8271337
TI  - Influence of climatic factors on rotavirus infection among children with acute
      gastroenteritis in Zaria, northern Nigeria.
AB  - Stool samples from 392 infants and young children attending various clinics in
      Zaria, Northern Nigeria from June 1986 to May 1987 were analysed by ELISA for the
      presence of rotaviruses. There was a prevalence of 27 per cent in these children
      with the virus being most prevalent in the first 6 months of life. This decreased
      with age until it was less than 10 per cent in children 3-5 years old. Although
      rotavirus was found to be present throughout the year; there was a much higher
      prevalence during the dry season (October to April) as compared to the wet
      season. Infection with the virus correlated inversely with relative humidity,
      vapour pressure and minimum temperature showing considerable influence of these
      climatic factors on rotavirus infection in children in Zaria.

PMID- 8271338
TI  - Arm circumference v. arm circumference/head circumference ratio in the assessment
      of malnutrition in rural Malawian children.
AB  - The arm circumference/head circumference ratio (AC/HC) was compared with arm
      circumference (AC) alone in the diagnosis of protein-energy malnutrition (PEM) in
      685 Malawian children between the ages of 3 and 48 months. The AC/HC ratio
      correlates well, r = 0.6863 (P < 0.001), with weight-for-age (WA). The
      sensitivity and specificity were calculated for both indicators compared to the
      NCHS reference standard of WA. Compared to 80 per cent WA, the 0.310 AC/HC cut
      off was 92 per cent sensitive and 41 per cent specific, while the 0.290 AC/HC cut
      off was 75 per cent sensitive and 74 per cent specific. AC alone in the 6-12
      month-old children was 75 per cent sensitive and 89 per cent specific at a cut
      off of 12.5 cm. In the children from 12 to 48 months with a cut-off of 13.5 cm
      the AC was 82 per cent sensitive and 70 per cent specific. The AC alone was more
      sensitive than AC/HC at all levels of specificity. Adding the HC to AC offered no
      advantage in screening for PEM in these children. In fact, if one were to use the
      standard 0.310 cut-off for AC/HC, the resulting low (41 per cent) specificity
      would identify such a large proportion of false positives as to make this ratio
      impractical for field use where it is most needed--in primary health care
      programmes with low resources which serve populations with high prevalences of
      PEM.

PMID- 8271339
TI  - A study of the importance of the enterotoxigenic E. coli in children with acute
      diarrhoea in Recife, Brazil.
AB  - Even today acute diarrhoea is a major cause of morbidity and mortality in young
      children. It is a serious public health problem in less-developed countries,
      primarily in households whose income is low. As such, it is one of the main
      causes of death, affecting the undernourished in particular. The potential
      enteropathogenic agents are distributed universally. However, there is a major
      difference in the prevalence, according to the areas and the characteristics of
      the population groups which were studied. In Brazil, since the 1970s, our
      attention has been drawn to the importance of the classic enteropathogenic
      strains of E. coli (EPEC) in the aetiology of diarrhoeal diseases, primarily
      those present in weaned infants in inner city neighbourhoods. On the other hand,
      Guerrant and co-workers, and Queiroz and co-workers found significant percentages
      of isolated colonies of enterotoxigenic coli (ETEC) in the stool material of
      children with symptoms of acute diarrhoea. In rural areas of less-developed
      countries the incidence of episodes of ETEC provoking diarrhoea is estimated to
      be between five and ten per person/year. Due to the social and medical gravity of
      acute diarrhoea, and to the lack of studies dealing with the aetiopathogenic role
      of the strains of ETEC in our area, we decided to analyse the frequency of
      isolation of ETEC in children with and without diarrhoea who were attending the
      out-patient department of the Instituto Materno Infantil de Pernambuco/IMIP.

PMID- 8271340
TI  - Infants and nutrition surveillance in Ethiopia.

PMID- 8271341
TI  - Rett syndrome in the developing world.

PMID- 8271342
TI  - Convulsions with fever of acute onset in school-age children in Benin City,
      Nigeria.
AB  - Of 92 school-age children who had convulsions with fever (CWF) of acute onset,
      seen in a 1-year period in an emergency room in Benin City, Nigeria, 49 per cent
      had malaria parasitaemia, 15 per cent bacterial meningitis, 8 per cent focal
      extracranial infections, and 1 per cent bacteraemia while 27 per cent had acute
      fever of undetermined origin. The prevalence of meningitis increased with
      presence of temperature > or = 40 degrees C (P < 0.01), focal seizures (P <
      0.05), and rousable coma (P < 0.05). Bacterial meningitis is an important illness
      in school-age children with CWF, although malaria parasitaemia is the commonest
      infection.

PMID- 8271343
TI  - Low birth weight (LBW) and structural adjustment programme in Nigeria.

PMID- 8271344
TI  - Epidemiology of nausea and vomiting of pregnancy and its relation to fetal
      outcome in a rural area.

PMID- 8271345
TI  - Diagnosis of hypothermia--a simple test?

PMID- 8271346
TI  - Traditional uvulectomy among preschool children in the far north eastern Nigeria.

PMID- 8271347
TI  - Acute bronchiolitis in Nigerian children.

PMID- 8271348
TI  - The silica content of faeces as an index of geophagia: its association with age
      in two Jamaican children's homes.

PMID- 8271349
TI  - Breastfeeding practices in urban and rural communities of west Bengal using
      standardized indicators.

PMID- 8271350
TI  - Is there an alternative to regular growth monitoring?

PMID- 8271351
TI  - Developing software in the Third World: Papua New Guinea provincial health
      information system.

PMID- 8271352
TI  - Liver dysfunction and energy source: results of a randomized clinical trial.
AB  - Controversy still exists regarding the role of the carbohydrate:fat ratio on
      liver function abnormalities associated with the administration of total
      parenteral nutrition (TPN). We designed a prospective clinical trail comparing
      standard carbohydrate-based TPN (8.5% amino acids, 50% dextrose, 7.5% of total
      calories from lipids) with an isocaloric lipid-based TPN (8.5% amino acids, 30%
      dextrose, 40% of total calories from lipids) in 43 patients exclusively receiving
      TPN > or = 2 weeks. Energy needs were calculated as basal energy expenditure x
      1.5. The mean daily calorie intake for patients who obtained carbohydrate-based
      TPN (CHO) was 2227 kcal, whereas the lipid-based TPN (LIP-CHO) group achieved a
      mean of 2310 kcal. Patients with preexisting liver disease were excluded. There
      was no significant difference in age or diagnosis between the groups. We
      monitored total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyl
      transferase, lactic dehydrogenase, serum glutamic oxaloacetic transaminase, and
      serum glutamic pyruvic transaminase. Initial liver-associated tests did not vary
      significantly between groups. Group mean values after 2 weeks of TPN were
      significantly different for total bilirubin (1.5 mg/dL in the CHO group compared
      with 0.7 in the LIP-CHO group, p < .05) and direct bilirubin (0.8 mg/dL in the
      CHO group compared with 0.3 mg/dL in the mixed substrate group, p < .05).
      Differences in mean values between groups were also noted for serum glutamic
      oxaloacetic transaminase, serum glutamic pyruvic transaminase, and lactic
      dehydrogenase. In conclusion, this prospective trial reveals that the use of a
      balanced energy source TPN solution prevents the abnormalities in liver
      associated tests commonly associated with TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271353
TI  - Effect of glutamine on protein synthesis in isolated intestinal epithelial cells.
AB  - The influence of glutamine on protein synthesis in small-bowel enterocytes was
      tested. Enterocytes were isolated from different levels of the villi of rat
      jejunum and were incubated in the presence of different glutamine concentrations,
      up to 3.4 mmol/L. Protein synthesis was determined by measuring incorporation of
      3H-phenylalanine into trichloroacetic acid-precipitated proteins. Glutamine, but
      no other amino acids, stimulated protein synthesis in enterocytes from all levels
      of the villi. A maximal effect was noted at a glutamine concentration of 0.67
      mmol/L, which is the normal plasma concentration. The amino acid stimulated the
      synthesis of both secreted and nonsecreted proteins. The stimulatory effect of
      glutamine on protein synthesis was blocked by the glutaminase inhibitor 6-diazo-5
      oxo-L-norleucine and was duplicated by equimolar concentrations of acetoacetate
      or 3-hydroxybutyrate. The results suggest that glutamine stimulates protein
      synthesis in small-bowel enterocytes and that this effect of glutamine is related
      to provision of energy. The findings are important because they suggest that
      increased protein synthesis may be one of the mechanisms by which glutamine
      exerts its protective effect on gut mucosa during critical illness.

PMID- 8271354
TI  - Direct assay of vitamins B1, B2, and B6 in hospitalized patients: relationship to
      level of intake.
AB  - High-performance liquid chromatography assays for vitamins B1 by erythrocyte
      thiamine pyrophosphate, B2 by plasma and urinary riboflavin, and B6 by plasma
      pyridoxal phosphate and urinary pyridoxic acid were used to evaluate the B
      vitamin status of hospitalized patients. Over an intake range of up to 3.4 mg of
      thiamine per day and up to 4.1 mg of riboflavin per day, erythrocyte thiamine
      pyrophosphate and urine and plasma riboflavin increased proportionately with
      intake. There was no relationship between B6 intake and blood levels. Rather, a
      constant blood level was maintained with an intake range of 0.5 to 4 mg/d, and
      urinary pyridoxic acid showed a linear increase proportionate to intake. There
      were extremely variable blood and urine concentrations of B vitamins noted in our
      patient population.

PMID- 8271355
TI  - Glutamine peptide does not improve gut barrier function and mucosal immunity in
      total parenteral nutrition.
AB  - In two separate experiments, three groups of 10 (first experiment) and 12 (second
      experiment) rats each were catheterized for the long term via the right jugular
      vein and fed one of the following dietary regimens for 7 days while in individual
      metabolism cages. The rat food control groups were fed powdered rat food. The
      total parenteral nutrition (TPN) formula for one group was enriched with the
      stable dipeptide L-alanyl-L-glutamine (ALA-GLN) equivalent to a 1% or 2%
      glutamine concentration. For the control TPN groups, the dipeptide was replaced
      by isonitrogenous amounts of alanine (ALA). In both experiments, bacterial
      translocation was promoted to a similar extent by the ALA-GLN and ALA TPN
      formulas compared with the rat food groups. Bacterial overgrowth in the cecum and
      intestinal atrophy, quantitated by the mucosal protein content, did not differ
      between ALA-GLN and ALA groups. The nitrogen balances of the three groups showed
      similar values in the second experiment. The secretory immunoglobulin A was
      measured in washings of the jejunum and ileum (soluble fraction) and in the
      homogenates of the gut mucosa (insoluble fraction). The secretory immunoglobulin
      A values of both fractions showed no difference between the ALA and ALA-GLN
      groups, irrespective of whether they were normalized for gut segment length or
      corrected for mucosal protein content. In conclusion from these results, the
      supplementation of TPN with glutamine does not seem to improve gut barrier
      function or mucosal immunity in unstressed rats.

PMID- 8271356
TI  - Short-chain fatty acids, lactate, and ammonia in ileorectal and ileal pouch
      contents: a model of cecal fermentation.
AB  - Fecal concentrations of total short-chain fatty acids were normal in 16 patients
      with ileorectal anastomoses (mean +/- SEM, 99.7 +/- 10.3 mmol/L) and 28 patients
      with ileal pouch-anal anastomoses (138.8 +/- 8.5 mmol/L) and did not differ from
      those in 14 healthy noncolectomized controls (130.7 +/- 12.6 mmol/L).
      Acetate:propionate:butyrate:isobutyrate+valerate+isovalerate ratios were similar
      in the ileorectum (71:12:12:5%) and in the colorectum (66:14:13:7%) of healthy
      noncolectomized controls, whereas the concentration of acetate was increased at
      the expense of the polypeptide-derived isobutyrate, valerate, and isovalerate in
      the ileal pouch (77:12:11:1%). Ammonia was accordingly significantly diminished
      in ileal pouch contents (28.8 +/- 3.2 mmol/L vs 45.2 +/- 4.1 mmol/L in controls)
      in contrast to concentrations in ileorectal contents (36.2 +/- 5.3 mmol/L).
      Concentrations of lactate were normal and low. Twenty-four-hour productions of
      total short-chain fatty acids in 16.6% fecal homogenates from both groups of
      patients were normal. Addition of saccharides (eg, glucose, starch, pectin,
      ispaghula husk) increased the production of acetate, propionate, and butyrate and
      decreased the production of ammonia and isobutyrate, valerate, and isovalerate,
      which was increased in homogenates with albumin added. This pattern of substrate
      fermentation was similar in homogenates from ileal pouch, ileorectum, and control
      colorectum. In conclusion, the concentrations of short-chain fatty acids,
      lactate, and ammonia indicate that ileorectal fermentation resembles normal
      colorectal fermentation in noncolectomized healthy individuals, whereas the
      fermentation in ileal pouch contents seems to be more carbohydrate
      predominated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271357
TI  - Elemental diet-induced immune suppression is caused by both bacterial and dietary
      factors.
AB  - Because it is unclear whether elemental diet-induced immune suppression is an
      indirect effect caused by the translocating bacteria or is directly caused by the
      elemental diet, we tested whether prevention of diet-induced bacterial
      translocation or disruption of the gut microflora ecology would prevent diet
      induced impaired lymphocyte function in a rat elemental diet model. Prevention of
      diet-induced bacterial translocation was accomplished by the addition of
      cellulose fiber or oral antibiotics (penicillin and streptomycin) to the
      elemental diet feeding regimen. Control groups consisted of rat food-fed and
      elemental diet-fed (4.25% amino acids; 28% glucose) rats. Immune function was
      quantitated by measuring the mitogen-induced blastogenic response of peripheral
      blood or splenic mononuclear cells to the mitogens concanavalin A and
      phytohemagglutinin. Bacterial translocation from the gut to the mesenteric lymph
      node and cecal bacterial population levels were measured in all groups. Although
      the incidence of elemental diet-induced bacterial translocation was reduced from
      100% to 25% (p < .01) by the addition of dietary fiber, fiber did not prevent
      diet-induced impaired lymphocyte function. Because fiber supplementation of the
      elemental diet did not completely prevent diet-induced intestinal bacterial
      overgrowth or bacterial translocation, the experiment was repeated in antibiotic
      decontaminated rats. Antibiotic decontamination completely prevented diet-induced
      intestinal bacterial overgrowth and bacterial translocation. Although antibiotic
      decontamination reduced the magnitude of lymphocyte mitogen suppression (p <
      .05), it was not fully effective in reversing the diet-induced lymphocyte
      suppression. These results indicate that elemental diet-induced lymphocyte
      blastogenic suppression is related to both bacterial and dietary factors.

PMID- 8271359
TI  - Xylitol normalizes the accelerated hepatic capacity for conversion of amino
      nitrogen to urea nitrogen in diabetic rats.
AB  - In diabetes, the capacity of urea nitrogen synthesis, ie, a substrate-independent
      measure of the hepatic conversion of amino nitrogen to urea nitrogen, is
      increased. Xylitol decreases urea synthesis in normal rats. Capacity of urea
      nitrogen synthesis and nitrogen balance were measured during intravenous alanine
      loading in control rats, rats with experimental diabetes (streptozocin 75 mg/kg),
      and rats with experimental diabetes infused with xylitol to 1 mmol/L. In control
      rats, capacity of urea nitrogen synthesis was 9.4 +/- 1.1 mumol/min per 100 g of
      body weight, and nitrogen balance -2.7 +/- 1.2 mumol/min per 100 g of body
      weight. In the diabetics, these values were markedly increased to 26.6 +/- 1.9
      and -16.3 +/- 2.1 mumol/min per 100 g of body weight, respectively (p < 0.01).
      The infusion of xylitol normalized these values to 11.2 +/- 1.0 and -3.6 +/- 2.1
      mumol/min per 100 g of body weight for capacity of urea nitrogen synthesis and
      nitrogen balance, respectively. Xylitol did not change glucagon or insulin.
      Xylitol improved the nitrogen economy of uncontrolled diabetic rats by decreasing
      urea synthesis. The mechanism is not settled, but it does not involve insulin or
      glucagon.

PMID- 8271358
TI  - Use of the soluble peptide gamma-L-glutamyl-L-tyrosine to provide tyrosine in
      total parenteral nutrition in rats.
AB  - Limited solubility restricts amounts of tyrosine (Tyr) in amino acid solutions
      used in total parenteral nutrition (TPN). Excess phenylalanine (Phe) is included
      in TPN for conversion to Tyr by liver Phe hydroxylase. However, this conversion
      is limited, especially in infants. We have confirmed that infants receiving TPN
      have low Tyr concentrations and high Phe/Tyr ratios in plasma compared with
      published values for enterally fed neonates. Tyr is important in the synthesis of
      proteins and other biomolecules, including catecholamines in the brain. We tested
      the soluble peptide gamma-glutamyl-tyrosine (Glu(Tyr)) as a possible precursor of
      Tyr in TPN. Groups of five rats were given infusions of TPN containing an amino
      acid mixture simulating a commercial formulation (group A), TPN in which Glu(Tyr)
      was substituted for half the Phe in the group A solution) (group B), or saline
      (group C). Control animals (group C) were fed rodent chow. Blood was sampled at 0
      time and daily for 4 days. Brains were collected at 96 hours, and aromatic amino
      acids in plasma and brains were measured by high-performance liquid
      chromatography. Throughout the experiment, plasma of animals in group A had
      significantly elevated Phe and reduced Tyr concentrations compared with control
      values; plasma concentrations in groups B and C were similar. In groups A and B,
      brain Tyr levels were 31% and 63% of control values, respectively. In group B,
      Glu(Tyr) was not detected in brains. These data suggest that supplementing
      current TPN mixtures with Glu(Tyr), which is stable in solution, can produce
      normal plasma Tyr concentrations and Phe/Tyr ratios and improve the supply of Tyr
      to the brain.

PMID- 8271360
TI  - The influence of parenteral glutamine and branched-chain amino acids on total
      parenteral nutrition-induced atrophy of the gut.
AB  - We tested the hypothesis that the provision of glutamine and branched-chain amino
      acids would reverse the gut atrophy that accompanies parenteral nutrition. Three
      hundred seventy-five rats were randomized into 15 groups to receive either
      conventional parenteral nutrition, rat food, glutamine-enriched parenteral
      nutrition (0.5% to 2.5%), branched-chain amino acid-enriched parenteral nutrition
      (0.8% to 2.0%), or glutamine plus branched-chain amino acid-enriched parenteral
      nutrition (0.5%/0.4% to 1.25%/1/0%). When compared with effects of conventional
      parenteral nutrition, the infusion of either glutamine or branched-chain amino
      acids partially reversed, in a dose-dependent manner, atrophy of the small bowel
      as assessed by gut weight (p < .05), mucosal weight (p < .05), villous height (p
      < .05), crypt cell production rate (p < .05), and mucosal protein concentration
      (p < .05). There was no effect on the large bowel. These results suggest that the
      parenteral infusion of either glutamine or branched-chain amino acids partially
      reverses the small-bowel atrophy that is associated with the infusion of
      solutions of conventional parenteral nutrients.

PMID- 8271361
TI  - Comparison of net protein utilization of milk protein mild enzymatic hydrolysates
      and free amino acid mixtures with a close pattern in the rat.
AB  - The nutritive value of two nitrogen-containing mixtures, one formed from small
      peptides (milk protein mild enzymatic hydrolysates) and the other consisting of a
      mixture of free amino acids having the same pattern except for glutamine, was
      measured in rats with and without experimental liver and exogenous pancreas
      dysfunction. For this purpose, 30 animals (group N) were fitted with an
      indwelling duodenal catheter; 36 animals (group L) also underwent ligation and
      resection of the biliopancreatic duct. After a 3-day recovery period, the animals
      in each group, divided into three equivalent batches, were given, for 10 days, a
      protein-free diet ad libitum and a twice-daily duodenal infusion (5 mL) of either
      saline, the small peptides, or the free amino acid mixture. The nitrogen
      containing mixtures provided 0.32 g of nitrogen per day. A blood sample (left
      side of the heart) was collected 1 hour before (five to six animals per batch)
      and after (five to six animals per batch) the last infusion for determination of
      glucose, insulin, and amino acids. After the animals were killed, their carcasses
      were freeze-dried, ground, and analyzed for nitrogen content. Under these
      conditions, the net protein utilization (the gain in body nitrogen in the animals
      infused with one of the two nitrogen-containing solutions in comparison with the
      animals infused with saline only divided by the nitrogen ingested) was
      calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271363
TI  - Phenytoin recovery from percutaneous endoscopic gastrostomy Pezzer catheters
      after long-term in vitro administration.
AB  - Four in vitro administration techniques were evaluated to determine which method
      would produce the least amount of phenytoin lost with long-term (14 days) dosing
      of Dilantin Kapseals (100 mg) or Dilantin suspension 125 mg/5 mL (92 mg) through
      20 French percutaneous endoscopic gastrostomy Pezzer catheters. The four in vitro
      techniques were (1) no dilution or irrigation, (2) irrigation with 10 mL of
      deionized water, (3) dilution with 10 mL of deionized water, and (4) dilution
      with irrigation. Similar doses and volumes (3.68 mL) of suspension and capsules
      were delivered to three separate catheters for each method every 8 hours for 14
      days. Each catheter was encased in a 200-mm glass water jacket and maintained at
      37 degrees C for the entire 14 days. Samples were collected 1 hour after
      administration on days 1, 3, 7, 10, and 14 and analyzed by high-performance
      liquid chromatography. The total mean percent change in initial phenytoin for
      each method was as follows (S = suspension, K = Kapseals, subscript number =
      method number): S1, -4.23 +/- 20.20 (mean +/- SD); S2, -7.63 +/- 14.04; S3, -0.14
      +/- 2.31; S4, 3.33 +/- 5.59; K1, -9.72 +/- 4.60, K2, 1.43 +/- 3.90; K3, -3.18 +/-
      5.59; and K4, 1.39 +/- 4.57.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271362
TI  - Intestinal, pancreatic, and hepatic effects of gastrointestinal hormones in a
      total parenteral nutrition rat model.
AB  - The adverse effects of long-term total parenteral nutrition (TPN) are well
      documented. Lack of gastrointestinal (GI) stimulation from oral feeding,
      reduction of GI hormone secretion, and interruption of enterohepatic circulation
      of bile may be found. TPN results in atrophy of the digestive system, intestinal
      bacterial overgrowth and translocation, liver cell damage, and gallstone
      formation. In addition, the increase incidence of sepsis of gut origin may lead
      to an increase in mortality. In some studies, results of the administration of GI
      hormones to patients receiving prolonged TPN suggest the possibility of reducing
      some of the adverse effects of long-term TPN. To evaluate the role of GI hormone
      in the prevention of adverse effects of TPN, we designed the following study: 50
      young adult male Wistar rats, weighing approximately 200 g, were divided into
      five equal groups. All animals received identical TPN infusate for 7 days. GI
      hormone was added to the TPN infusate as follows: Group A (control) received no
      GI hormone, group B was given glucagon at a dosage of 330 micrograms/kg per day,
      group C was administered cholecystokinin 2 Ivy dog units twice a day, group D
      received secretin 2 clinical units twice a day, and group E was given both
      cholecystokinin and secretin at the dosages stated for groups C and D.
      Maintenance of mucosal brush-border hydrolase activity was found in group B.
      Neither atrophy of the pancreas nor hypoplasia of intestinal villi was observed
      in groups C and D. Group C showed improvement of liver function-associated tests,
      better weight gain, and acceleration of enterohepatic circulation of
      bile.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271364
TI  - Effect of arginine-enriched total parenteral nutrition on the host-tumor
      interaction in cancer-bearing rats.
AB  - By using a transplantable Yoshida sarcoma in a rat total parenteral nutrition
      model, we measured the effectiveness of an arginine-enriched amino acid solution
      (AI-82) in terms of leucine kinetics and nitrogen balance as indicators of host
      tumor nutrition interaction compared with that of a conventional amino acid
      solution (Proteamin12). When tumor-bearing rats received isocaloric total
      parenteral nutrition solutions for 7 days, AI-82 significantly improved host
      nitrogen balance and significantly decreased the tumor-nitrogen trap throughout
      the experimental period. Leucine kinetics of whole body and tissues were also
      determined by a 4-hour continuous infusion of each total parenteral nutrition
      solution containing 14C-leucine. Significantly increased whole-body leucine
      oxidation (p < .01) without an increase in leucine release from normal tissues
      was observed in the AI-82 group. Total incorporation of 14C-leucine into whole
      muscle was significantly elevated (p < .05) without changes in muscle protein
      degradation in the AI-82 group. In the whole tumor, AI-82 tended to decrease
      total incorporation of 14C-leucine, but there was no difference in leucine
      release caused by protein breakdown between the two groups. These findings
      suggest that AI-82 can improve the nutritional status of the host over that of
      the tumor.

PMID- 8271365
TI  - Nutrition support of a pregnant comatose patient via percutaneous endoscopic
      gastrostomy.
AB  - A pregnant woman was comatose after a motor vehicle accident at 13 weeks'
      gestation. The nutritional needs of the patient were supported by tube feedings
      after percutaneous endoscopic gastrostomy. Clinical management was required for
      nutrition support, infection, and fetal development. At 37 weeks' gestation, a
      normal 3640-g male infant was delivered by cesarean section. This represents the
      first case report of a successful pregnancy outcome after percutaneous endoscopic
      gastrostomy for enteral nutrition support of a pregnant comatose patient.

PMID- 8271366
TI  - Comparison of gas exchange measurements with a mouthpiece, face mask, and
      ventilated canopy.
AB  - This study compared gas exchange measurements obtained by using a mask,
      mouthpiece, and ventilated canopy in 30 normal, healthy volunteers. The
      ventilated canopy and its gas analyzers had an accuracy for oxygen consumption of
      98.0 +/- 0.8% and for carbon dioxide production of 100.1 +/- 1.1%. The study
      indicates that the apparatus used for gas exchange measurement will significantly
      affect the measurements. The magnitude of the effect is a significant 7.9%
      increase for oxygen consumption with a mouthpiece and a significant 7.1% increase
      with a face mask. Carbon dioxide production was significantly increased 10.2%
      with a mouthpiece and 4.1% with a face mask. There were no differences in the
      respiratory quotient. The specific purpose for collecting gas exchange
      measurements will determine whether these differences are of practical
      significance.

PMID- 8271367
TI  - Resting energy expenditure, caloric intake, and short-term change in HIV
      infection and AIDS.

PMID- 8271368
TI  - Marked resistance of normal subjects to tube-feeding-induced diarrhea: the role
      of magnesium.

PMID- 8271369
TI  - Circulatory indirect calorimetry in the critically ill.

PMID- 8271370
TI  - Contamination of enteral feeding systems in the nosocomial environment.

PMID- 8271371
TI  - [The structure of the virion of HIV and its entrance into the cell].

PMID- 8271372
TI  - [Lentiviruses and origin of HIV].

PMID- 8271373
TI  - [How to evaluate anti-HIV activity].

PMID- 8271374
TI  - [A novel soluble factor from CEM.T cell line can inhibit the replication of HIV-1
      in vitro].

PMID- 8271375
TI  - [Polyphenols as anti-HIV agents].

PMID- 8271376
TI  - [Development of lipophilic 6-halo-2',3'-dideoxypurine nucleoside and derivatives:
      approach to develop CNS-targeting anti-HIV agents].

PMID- 8271377
TI  - [Kynostatin (KNI)-272--a rationally designed tripeptide inhibitor of HIV
      protease].

PMID- 8271378
TI  - [A synthetic peptide "T22" as anti-HIV agents].

PMID- 8271379
TI  - [Naphthalenedisulfonic acid (NDS) derivatives as anti-HIV agents].

PMID- 8271381
TI  - [Anti-HIV activity of sulfated gangliosides].

PMID- 8271380
TI  - [Sulfated curdlan and sulfated alkyl oligosaccharide as anti-viral agent].

PMID- 8271382
TI  - [Glycosidase inhibitors as anti-HIV agents].

PMID- 8271383
TI  - [Polyoxometalate "PM-104" as anti-HIV agent].

PMID- 8271384
TI  - [Anti-HIV-1 activities of crude drug, shikon (Lithospermi radix), in vitro].

PMID- 8271385
TI  - [Human immunodeficiency virus--its virological characteristics].

PMID- 8271386
TI  - [Anti-HIV-1 p17 antibody as anti-HIV agent].

PMID- 8271387
TI  - [Anti-carbohydrate monoclonal antibodies against human immunodeficiency virus].

PMID- 8271388
TI  - [Role of interleukin-6 in human immunodeficiency virus type 1 infection].

PMID- 8271389
TI  - [Anti-HIV genes: strategies for gene therapy of AIDS].

PMID- 8271390
TI  - [Anti-HIV compounds].

PMID- 8271391
TI  - [Current diagnosis--screening and diagnosis of HIV infections].

PMID- 8271392
TI  - [HIV p24 antigen in blood for diagnosis of HIV infections].

PMID- 8271393
TI  - [The structure of HIV virions].

PMID- 8271394
TI  - [Detection of HIV-RNA in blood].

PMID- 8271395
TI  - [Detection of proviral DNA from infected cells for diagnosis of HIV infections].

PMID- 8271396
TI  - [Detection of antibodies to HIV and HIV-genes in saliva and urine].

PMID- 8271397
TI  - [Treatment--medical management of HIV carrier].

PMID- 8271398
TI  - [Structure and function of HIV genes].

PMID- 8271399
TI  - [CD4-derivatives therapy of HIV carriers].

PMID- 8271400
TI  - [Interferon therapy of HIV carriers].

PMID- 8271401
TI  - [BRM and drug combination therapy of HIV carriers].

PMID- 8271402
TI  - [Targets and possible therapeutic interventions for HIV carriers].

PMID- 8271403
TI  - [Early treatment in HIV infection].

PMID- 8271404
TI  - [Structure and function of HIV gene products].

PMID- 8271405
TI  - [Neuropsychiatric disorders in AIDS].

PMID- 8271406
TI  - [Pulmonary involvement in AIDS].

PMID- 8271407
TI  - [Kaposi's sarcoma in AIDS].

PMID- 8271408
TI  - [Endocrine abnormalities in HIV infection].

PMID- 8271409
TI  - [Hepato-biliary and pancreatic disorders in AIDS].

PMID- 8271411
TI  - [Ophthalmic manifestations in AIDS].

PMID- 8271410
TI  - [Gastrointestinal disorders in AIDS].

PMID- 8271412
TI  - [Bacterial (except acid-fast bacteria) infections in AIDS].

PMID- 8271413
TI  - [Tuberculosis and atypical mycobacterial infection in HIV-infected patients].

PMID- 8271414
TI  - [Virus diseases in AIDS].

PMID- 8271415
TI  - [Regulatory mechanism of HIV gene expression].

PMID- 8271416
TI  - [Protozoan infections in AIDS].

PMID- 8271417
TI  - [Mycosis in AIDS].

PMID- 8271418
TI  - [Syphilis in AIDS].

PMID- 8271419
TI  - [HIV infection in infants and children].

PMID- 8271420
TI  - [Epidemiology of AIDS in Japan].

PMID- 8271421
TI  - [Epidemiological data of HIV/AIDS in the world].

PMID- 8271422
TI  - [Estimation and projection of HIV/AIDS epidemic].

PMID- 8271423
TI  - [Adult sexual behavior and HIV infection among homosexual and bisexual people].

PMID- 8271424
TI  - [Heterosexual transmission of HIV-1].

PMID- 8271425
TI  - [Blood transfusion and HIV infection].

PMID- 8271426
TI  - [Misunderstanding and prejudice concerning non-contagious routes of HIV].

PMID- 8271427
TI  - [Preventive methods against HIV transmission].

PMID- 8271428
TI  - [Prevention of nosocomial infection with HIV].

PMID- 8271429
TI  - [Protective strategy against human immunodeficiency virus and other retroviral
      infection on laboratory work].

PMID- 8271430
TI  - [Prevention of AIDS on dental treatment].

PMID- 8271431
TI  - [AIDS control in Japan].

PMID- 8271433
TI  - [AIDS education at home].

PMID- 8271432
TI  - [AIDS vaccine--its strategies and prospects].

PMID- 8271434
TI  - [AIDS education in schools].

PMID- 8271435
TI  - [Education of AIDS in community].

PMID- 8271436
TI  - [Education programs for AIDS in companies].

PMID- 8271437
TI  - [Telephone counseling for AIDS].

PMID- 8271438
TI  - [Care for people with HIV and the infringement of human rights].

PMID- 8271439
TI  - [AIDS--lawsuits and human rights].

PMID- 8271440
TI  - [Explanations, guidances and advices how to fight against HIV infections for
      PWAs].

PMID- 8271441
TI  - [The counseling for persons with HIV infection].

PMID- 8271442
TI  - [HIV nef gene and nef protein].

PMID- 8271443
TI  - [Terminal cares for HIV infected subjects].

PMID- 8271444
TI  - [Animal model of human AIDS: murine acquired immunodeficiency syndrome virus].

PMID- 8271445
TI  - [HIV superinfection].

PMID- 8271446
TI  - [HIV-2 infection--investigation trend].

PMID- 8271447
TI  - [Development of HIV-based retrovirus vector].

PMID- 8271448
TI  - [HIV-1, V3-loop binding protein(s) (V3-LBP)].

PMID- 8271449
TI  - [Cell lines for HIV study].

PMID- 8271450
TI  - [HIV vif, vpr, vpu genes: structure and function].

PMID- 8271451
TI  - [Role of soluble IL-6 signal transducer (gp130) in HIV infection].

PMID- 8271452
TI  - [Target cells for HIV and the mechanism of its penetration into the cells].

PMID- 8271453
TI  - [Intracellular growth cycle of HIV].

PMID- 8271454
TI  - [Genetic variability in HIV].

PMID- 8271455
TI  - [Methods for HIV-isolation and HIV gene-analysis].

PMID- 8271456
TI  - [Molecular epidemiology of HIV-1 infections].

PMID- 8271457
TI  - [Recent progress in esophageal varices therapy].

PMID- 8271458
TI  - [The utility of endoscopic ultrasonography (EUS) in endoscopic mucosal resection
      of early gastric cancer].
AB  - The utility of EUS was evaluated in 27 patients with early gastric cancer
      undergoing endoscopic mucosal resection over the past 2 years. Accuracy of the
      assessment of depth of cancerous invasion was studied in 16 patients undergoing
      EUS before endoscopic mucosal resection. Patients showing no changes in the
      submucosal (sm) layer or below on EUS included 15 with mucosal (m) cancer and one
      with sm cancer showing very slight infiltration. Seven patients with m cancer, a
      negative stump, and no ulcer in the cancer focus at endoscopic mucosal resection,
      were followed up for more than 1 year after endoscopic mucosal resection. On EUS,
      four patients showed Ul-IIs changes resembling benign ulcers, two showed Ul-IIIs
      changes and two showed no changes in the sm layer or below. All patients were
      negative for cancer in follow up biopsies. No lymphadenopathy was observed. EUS
      was effective in diagnosing the depth of cancerous invasion in patients
      undergoing endoscopic mucosal resection and also in clarifying changes in the sm
      and deeper layers during follow up.

PMID- 8271459
TI  - [Significance of quantitative and qualitative analysis of fecal alpha 1
      antitrypsin in gastric cancer patients].
AB  - The levels of fecal alpha 1-antitrypsin (alpha 1-AT) were significantly high in
      advanced gastric cancer patients, compared with those in healthy control subjects
      and early gastric cancer patients. As the background, a process was assumed that
      excessive alpha 1-AT which flowed into the stomach through the cancerous lesion
      is saved from rapid proteolysis in the gastric juice of hypoacidity and proceeds
      to the small intestine. A molecular weight 38000 form of alpha 1-AT was detected
      in all of the stools of the control subjects and the gastric cancer patients by
      Western blotting analysis, and which was shown to lack its sugar chain by crossed
      immunoelectrophoresis (CIE) and crossed immuno-affino-electrophoresis (CIAE)
      analysis.

PMID- 8271460
TI  - [Long-term efficacy of low residue diet for the maintenance of remission in
      patients with Crohn's disease].
AB  - The long term efficacy of low residue diet (LRD) for the maintenance of remission
      in patients with Crohn's disease was studied. The patients consisted of 60 with
      quiescent Crohn's disease who were given LRD (Clinimeal or Ensure Liquid) for
      maintenance therapy for more than one year (average 2.4 years) after discharge
      from our institute. On the basis of the quantity of LRD given per day, the
      patients were classified into three groups: A; O to 799 kcal a day, B; 800 to
      1599 kcal a day and C; more than 1600 kcal a day. The remission rate and the
      avoidance rate of admission were calculated and compared among three groups. The
      remission rate in group C was significantly higher than those in groups A and B.
      The avoidance rates of admission in groups B and C were significantly higher than
      that in group A. These results suggest that drinking of LRD at home is useful for
      the maintenance of remission in patients with Crohn's disease and that the effect
      of LRD depends on the quantity of LRD given per day.

PMID- 8271461
TI  - [A clinical decision analysis to assess therapeutic modalities for symptomatic
      gallstones with respect to patient's quality of life and cost-effectiveness].
AB  - A clinical decision analysis was performed to assess new therapeutic modalities
      for symptomatic gallstones with respect to patient's quality of life (QOL) and
      cost-effectiveness. A decision tree-based state transition model (Markov
      approach) implemented to simulate a five-year period of follow-up was
      constructed. Non-surgical treatments were superior to surgery in enhancing
      patient's QOL. This advantage was dependent upon the efficacy of non-surgical
      treatments (stone clearance rate) and patient's age. The optimal candidates were
      patients with a single radiolucent stone less than 2 cm in diameter for
      extracorporeal shock-wave lithotripsy (ESWL), and patients with multiple floating
      stones for oral dissolution, respectively, especially in the elderly. ESWL was
      less cost-effective than laparoscopic cholecystectomy (LC). ESWL was superior to
      LC in enhancing patient's utility, but more expensive than LC. LC was
      economically cost-effective and superior to open cholecystectomy in enhancing
      patient's QOL for all eligible patients. LC appears to be the therapeutic
      modality of first choice for the majority of patients with symptomatic
      gallstones. In conclusion, the results of our analysis suggest the followings.
      Non-surgical treatments have an advantage over surgery in enhancing patient's QOL
      and are acceptable alternatives to surgery on the basis of their optimal
      indications and laparoscopic cholecystectomy is the new standard therapeutic
      modality in the treatment of symptomatic gallbladder stones.

PMID- 8271462
TI  - [Activation of peritoneal macrophages in rats with caerulein-induced
      pancreatitis].
AB  - We examined the stimulatory state of peritoneal macrophages (M phi) in caerulein
      induced pancreatitis. Edematous pancreatitis was developed by the intravenous
      continuous injection of caerulein (5 micrograms/kg/hr) for 4 hr. Thereafter
      peritoneal M phi were collected and the activity for free radical production was
      measured by the reduction of nitro blue tetrazorium in the presence of phorbol
      myristate acetate. The increase in free radical production reached a statistical
      significance at 12 hr and a maximum at 20 hr after the beginning of caerulein
      infusion. These results suggested that the peritoneal M phi are activated even in
      mild edematous pancreatitis, and that their activation is involved into the
      mechanism of the development of remote organ failure in acute pancreatitis.

PMID- 8271463
TI  - [A case report of the cytomegalovirus reactivation on the gastric mucosa
      surrounding early gastric cancer associated with nephrotic syndrome].

PMID- 8271464
TI  - [A case of gastrointestinal GVHD (graft-versus-host disease) and cytomegalovirus
      ileitis with bone marrow transplantation].

PMID- 8271465
TI  - [Combined analysis of tissue DNA for diagnosis of cytomegalovirus enteritis:
      report of a case].

PMID- 8271466
TI  - [Delayed formation of liver abscess following transcatheter arterial oily
      chemoembolization for hepatocellular carcinoma].

PMID- 8271467
TI  - [A case of acute hepatitis A with renal failure caused by fibrinogen deposits].

PMID- 8271468
TI  - [A case of intrahepatic cholesterol gallstone associated with various hepatic
      inflammatory granulation].

PMID- 8271469
TI  - [A case of prolonged liver injury caused by low dose of acetaminophen--the
      involvement of other multiple drugs such as Proheparum and Mazulene-S was
      considered in this drug-induced hepatitis].

PMID- 8271470
TI  - [A case of idiopathic portal hypertension associated with systemic lupus
      erythematosus].

PMID- 8271471
TI  - [A case of tuberculous peritonitis complicating old tuberculous colitis and
      pulmonary tuberculosis: diagnostic contributions of polymerase chain reaction
      (PCR)].

PMID- 8271472
TI  - [Hypersensitivity to lipopolysaccharide of Kupffer cells in experimental acute
      pancreatitis].

PMID- 8271473
TI  - [Clinical significance of 3 beta, 7 beta-dihydroxy-5 beta-cholan-24-oic acid
      (isoUDCA) in serum during administration of ursodeoxycholic acid].

PMID- 8271474
TI  - [Quantification of Helicobacter pylori in the gastric mucus by competitive PCR
      using synthetic DNA fragments].

PMID- 8271475
TI  - Biosynthesis of the blood group P antigen-like GalNAc beta 1-->3Gal beta 1-
      >4GlcNAc/Glc structure: kinetic evidence for the responsibility of N
      acetylglucosaminyltransferase.

PMID- 8271476
TI  - Low temperature dependent IgG3 subclass antibody with low avidity to C100-3
      antigen derived from hepatitis C virus in voluntary blood donors.
AB  - The presence of an antibody which reacts strongly at lower temperatures to C100-3
      antigen derived from the hepatitis C virus (HCV) was demonstrated in blood
      donors' sera. These sera reacted with the antigen most strongly at 4 C and most
      weakly at 37 C and are termed 'cold antibody group'. The cold antibody group
      reaction was specifically inhibited with soluble C100-3 antigen. Cold antibody
      bound to C100-3 antigen at 4 C was dissociated at 37 C and was isolated in this
      manner. Low temperature-dependent anti C100-3 antibody was shown to be
      predominantly IgG3 subclass by ELISA using anti-human IgG subclass antibody. This
      IgG3 antibody was dissociated from antigen with 6M urea, demonstrating its low
      avidity. HCV-RNA was demonstrated in two of five samples. Therefore, to achieve
      more effective prevention of post-transfusion hepatitis C, we propose the
      incorporation of programs to detect low temperature-dependent low-avidity
      antibody against HCV-related antigen.

PMID- 8271477
TI  - Antigenic analysis of coxsackievirus B3 with monoclonal antibodies.
AB  - All the 16 mouse monoclonal antibodies (McAbs) raised against Nancy strain of
      coxsackievirus B3, CoxB3(N), were type 3-specific. The reactivity of CoxB3(N) to
      this McAb panel during the serial passages showed a variation. Three field
      isolates of CoxB3, all neutralizable with the reference Anti-CoxB3 hyperimmune
      serum, were checked for the reactivities with the McAb panel. The isolates from
      the patients in Fujiang reacted with 12 McAbs and variably with the remaining
      four McAbs. On the basis of the reactivities with different virus strains, the
      McAbs were found to fall into four groups possibly corresponding to at least four
      epitopes. A considerable antigenic variation of CoxB3 was thus suggested.

PMID- 8271478
TI  - 17th Seiriken Conference. March 3-7, 1992. Frontiers in optical neurosciences.
      Proceedings.

PMID- 8271479
TI  - Optical monitoring of physiological activity: a brief history.

PMID- 8271480
TI  - External ATP induced increase in intracellular free calcium in mammalian atrial
      myocytes.
AB  - Extracellularly applied ATP elicited a transient increase in intracellular free
      calcium concentration ([Ca2+]i) measured by fura-2 fluorescence digital imaging
      microscopy in isolated rabbit and guinea-pig atrial myocytes. In the
      electrophysiological study, ATP induced a transient depolarization of the
      membrane potential due to activation of a rapidly desensitizing inward current.
      Our results indicate that in mammalian atrial myocytes, ATP evoked transient
      increase in [Ca2+]i through release of internally stored Ca2+ associated with
      inflow of external Ca2+, mainly through L-type Ca channels which were voltage
      activated secondarily to ATP-induced conductance changes.

PMID- 8271481
TI  - Mechanically induced calcium signal in mammary epithelial cells.
AB  - In mouse mammary epithelial cells, mechanical stimulation of a cell induced an
      increase of intracellular Ca2+ concentration (Ca2+i), which spread from the
      stimulated cell to the surrounding cells with a conduction velocity of about 10
      microns/s. The Ca2+i signal was transmitted between isolated cells or separated
      colonies, where there was no physical contact between them. The flow of medium
      changed the spreading pattern of Ca2+ wave. The Ca2+ wave was induced even in
      Ca(2+)-free solution. These findings suggested that a certain factor was released
      from stimulated cell to extracellular medium and it induced the Ca2+i increase
      from intracellular store in the surrounding cells.

PMID- 8271482
TI  - Mastoparan evokes exocytosis without Ca2+ movement in adrenal chromaffin cells.
AB  - The secretagogue action of mastoparan, a tetradecapeptide from wasp venom, was
      studied in adrenal chromaffin cells. Pulsatile stimulation with mastoparan evoked
      a sharp transient release of CA in a dose-dependent manner, as measured by real
      time monitoring system. The secretagogue action of mastoparan in these cells was
      apparently independent of extracellular Ca2+, and may not require the
      intracellular mobilization of Ca2+ since BAPTA failed to block its secretagogue
      action. Video-imaging data also suggested that mastoparan evokes CA release
      without an increase in the intracellular Ca2+. In addition, visualization of
      exocytotic events with video-enhanced light microscopy demonstrated that CA
      release evoked by mastoparan at relatively low concentration was indeed mediated
      by exocytotic process, not by cell lysis.

PMID- 8271483
TI  - Glucose metabolism by rat pancreatic beta-cells produces dual change in cytosolic
      Ca2+.
AB  - It was reported that glucose stimulation initially lowers as well as subsequently
      raises the cytosolic free calcium concentration ([Ca2+]i) in pancreatic islet
      cells from hyperglycemic ob/ob mice. In the present study, [Ca2+]i in single
      pancreatic beta-cells from normal rats was measured by fura-2 microfluorometry.
      Following elevation of the glucose concentration to 16.7 mM from either 2.8 mM
      (basal) or 5.6 mM, an initial decrease and subsequent increase in [Ca2+]i were
      demonstrated. An elevation of the glucose concentration from 2.8 to 5.6 mM
      induced the decrease in [Ca2+]i but not usually the increase. Removal of
      extracellular Ca2+ eliminated the increase in [Ca2+]i without affecting the
      decrease. Mannoheptulose and KCN, inhibitors of glucose metabolism and TCA cycle,
      eliminated both the decrease and increase in [Ca2+]i. These results demonstrate
      that the glucose-induced bimodal change in [Ca2+]i is a physiological response of
      islet beta-cells, and that the decrease and increase in [Ca2+]i are generated by
      mutually-independent mechanisms which are operated through glucose metabolism by
      islet beta-cells.

PMID- 8271484
TI  - Periodic bursting of cultured cortical neurons in low magnesium: cellular and
      network mechanisms.
AB  - The origin of the 0.1 Hz bursting of cultured rat cortical neurons in zero Mg2+
      was studied by whole-cell recording, fluo-3 Ca2+ imaging, and multi-unit
      electrode array recording. A model is proposed in which spontaneous synaptic
      currents act as a random pacemaker.

PMID- 8271485
TI  - Optical rotation signal of nerve and the Faraday effect.
AB  - The polarity of the optical rotation signal, recorded from the lobster nerve, was
      reversed when the direction of incident light was changed by 180 degrees. This is
      a property of the Faraday rotation, but the magnetic field by the action current
      was too small to explain the size of the observed signal.

PMID- 8271486
TI  - High resolution microfluorometry of Ca2+ signalling in dendrites and spines of
      central neurons.
AB  - Using an upright microscope and an interface type slice chamber for
      epifluorometric imaging of fura-2 injected neurons in brain slice is particularly
      convenient to obtain good spatial resolution. Using this approach we found that
      muscarinic activation uncouples K-channel activation from intradendritic Ca and
      that postsynaptic spines represent independent compartments for Ca-activated
      processes when activated synaptically.

PMID- 8271487
TI  - Local calcium regulatory compartments in neurons.
AB  - We have demonstrated that calcium concentration is under local control in two
      different systems: hippocampal pyramidal cell dendritic spines, and developing
      grasshopper pioneer neuron axons. Controllable, photoinduced damage to fura-2
      filled processes was used for generating defined, reliable cytoplasmic calcium
      transients to demonstrate these local calcium regulatory compartments.

PMID- 8271488
TI  - Excitation-induced Ca2+ dynamics in sympathetic neurons measured with
      conventional epifluorescence and confocal UV laser-scanning microscopes.
AB  - A depolarization-induced rise in intracellular Ca2+ in cultured bullfrog
      sympathetic ganglion cells depended non-linearly on Ca2+ influx and membrane
      depolarization, spread inwardly faster than that without Ca(2+)-induced Ca2+
      release (CICR), and was blocked by dantrolene and ryanodine. Ca2+ entry and a
      graded activation of CICR thus induce the "Ca2+ transient."

PMID- 8271489
TI  - Neutral red: a specific fluorescent dye in the cerebellum.

PMID- 8271490
TI  - Confocal laser-scanning microscopical image of the distribution of intracellular
      organelles in cochlear outer hair cells.
AB  - Confocal laser-scanning microscopy was used to observe cytosolic Ca2+, organelles
      and cytoskeleton in the cochlear outer hair cell. The characteristic distribution
      of the subsurface cistern was observed in coincidence of the infracuticular
      network of F-actin and membrane-bound calcium, suggesting the source of Ca2+ for
      the actin-mediated process.

PMID- 8271491
TI  - Sodium extrusion mechanism in mammalian cochlear outer hair cell.
AB  - Intracellular sodium concentration ([Na+]i) in isolated outer hair cells (OHCs)
      of guinea pig cochlea was measured by microfluorimetric method using sodium
      binding benzofuran isophthalate. An application of ouabain increased [Na+]i. Our
      results suggest that OHCs have the definite activity of Na+/K+ ATPase.

PMID- 8271492
TI  - Fluorescent dye (DiI) reveals the sensory cells in the lingual epithelium: a
      confocal laser scanning microscopic study.
AB  - Fluorescent carbocyanine dye was applied to the glossopharyngeal nerve of
      axolotls fixed with paraformaldehyde. Three cell types in the lingual epithelium
      were transneuronally labeled: chemosensory taste receptor cells and presumably
      mechanosensory basal cells in the taste buds, and epithelial cells with unknown
      function in the non-taste lingual epithelium.

PMID- 8271493
TI  - Confocal imaging of mossy fiber growth in live hippocampal slices.
AB  - Acutely isolated slices of developing rat hippocampus have been used to study
      axon growth and synapse formation. Mossy fibers, which are the axons of dentate
      granule cells, were labeled in living brain slices by injection of a fluorescent
      membrane dye (DiI or DiO) into the dentate gyrus. Time-lapse observations were
      made in area CA3 at a time when mossy fibers are normally growing in and forming
      en passant synapses with pyramidal neurons. Single scan images were collected at
      1-2 min intervals over a period of several hours using a scanning laser confocal
      microscope. At the tips of growing mossy fibers were highly motile growth cones
      with several filopodia and small lamellae. Labeled fibers typically extended at
      rates up to 15 microns/h, but occasionally individual axons abruptly stopped
      elongating and the leading growth cone became quiescent. In addition, dynamic
      filopodia-like structures were found to be associated with axonal varicosities
      proximal to the leading growth cone. We are currently pursuing methods to
      determine whether these motile activities correlate with synapse formation.

PMID- 8271494
TI  - Response of aged neurons to super-hypotonic environment.
AB  - Cultured sensory neurons from aged mice (24 months old) lost capability of cell
      volume auto-regulatory mechanism after the rapid treatment with a hypotonic
      solution of 1/4 the normal osmolarity or lower. However, they could survive and
      extend neurites in super-hypotonic media such as 1/4 osmolar and even 1/8 osmolar
      culture media when the osmolarity was reduced gradually to such a low level.

PMID- 8271495
TI  - Organelle transport in cultured smooth muscle cells of the rabbit basilar artery.
AB  - Organelle transport in cultured smooth muscle cell from the rabbit basilar artery
      was observed. The organelles transported in the cells were moving in both
      centrifugal and centripetal directions. The instantaneous velocities of
      organelles were 0.84 +/- 0.36 micron/s in the centrifugal direction and 0.86 +/-
      0.48 micron/s in the centripetal direction. The transported organelles consisted
      mainly of lysosomes (67.5%) and mitochondria (29.0%).

PMID- 8271496
TI  - Optical measurement of action potential activity in invertebrate ganglia.
AB  - With a voltage-sensitive dye and an array of silicon photodiodes we monitored the
      action potential activity of a large fraction of the cells in the Aplysia
      abdominal ganglion during the gill-withdrawal reflex. This capability allowed a
      direct determination of the spread of sensory information within the 1,000
      neurons of the ganglion. Surprisingly, approximately 30% of the neurons are
      activated by a light touch to a small area of siphon skin. It is likely that many
      other neurons also receive large synaptic potentials, either excitatory or
      inhibitory, and thus even a very mild and restricted stimulus will have widely
      distributed effects. It seems to us that these results will force a more
      pessimistic view of the present understanding of the neuronal basis of apparently
      simple behaviors.

PMID- 8271497
TI  - Exocytosis in the growth cone of differentiated chromaffin cells induced by
      electrical stimulation.
AB  - In order to elucidate the mechanism involved in the specialized function of the
      nerve terminals, we studied the growth cone of cultured chromaffin cells using a
      video-enhanced Nomarski microscope. At a very high magnification, we found rapid
      and discrete morphological changes of small granules induced by electrical
      stimulation. Since they shared properties similar to those of the exocytotic
      responses found in granules in the cell body region, we conclude that they also
      reflect exocytosis of transmitter-containing granules. The frequency of the
      exocytotic responses was highest in the growth cone, lower in the cell body
      region, and none in the thin shaft of the neurite, suggesting a functional
      differentiation in the growth cone. Similar differentiation may be instrumental
      in physiological functions of the neuronal growth cone in vivo.

PMID- 8271498
TI  - Rapid filopodial sprouting induced by electrical stimulation in nerve terminals.
AB  - Direct electrical stimulation of terminals of neurite-like extensions of cultured
      chromaffin cells and neuronally differentiated PC12 cells induced rapid sprouting
      of filopodia in a Ca dependent manner. Repetitive stimulation could produce
      filopodia with greater ease. Their formation could not be significantly
      suppressed by treatment with cytoskeletal blocking agents. Filopodial sprouting
      was localized to the terminal region only. This response may occur at the growth
      cone in vivo playing a role in neuronal development.

PMID- 8271499
TI  - Elongation of growth cone filopodia observed with video-enhanced differential
      interference contrast microscopy.
AB  - Dynamics of filopodia configuration from growth cones of neurons isolated from
      the rat central nervous system were analyzed by using video-enhanced differential
      interference contrast microscopy. Rapid elongation of filopodia from growth cones
      and dendrites was observed when high K+ Krebs solution was applied to the growth
      cones. The maximum speed of the elongation was about 1 micron/s. The filopodia
      suspended in control Krebs solution moved at random. Retraction of the filopodia
      was observed within a few minutes after high K+ stimulation.

PMID- 8271500
TI  - Functional architecture of the hippocampus studied by the optical method with a
      potential sensitive dye.

PMID- 8271501
TI  - Real-time imaging and modeling of activity in olfactory bulb circuits underlying
      odor processing.

PMID- 8271502
TI  - Heterogeneous expression of Ca2+ permeable glutamate receptor subtypes in
      cultured hippocampal neurons as revealed by Ca(2+)-fluorometry.

PMID- 8271503
TI  - Accommodation to maintained stimuli in the ampullae of Lorenzini: how an
      electroreceptive fish achieves sensitivity in a noisy world.

PMID- 8271504
TI  - Morphology and physiology of auditory interneurons of the bushcricket Gampsocleis
      gratiosa.
AB  - Seven types of auditory interneurons were characterized from the prothoracic
      ganglion of the bushcricket. They are sensitive in the range of 7-18 kHz and fire
      with distinct discharge patterns. They encode sound intensity and temporal
      parameters in various way. They show significant directional sensitivity,
      dependent on sound frequency. The acoustic tracheal system can partly account for
      the directional hearing of the bushcricket.

PMID- 8271505
TI  - Behavioural evidence for parallel information processing in the visual system of
      insects.
AB  - Many flying insects display remarkable visual agility in capturing prey or
      pursuing a potential mate. They are capable of detecting, recognising, tracking
      and capturing a rapidly moving object on the wing. These manoeuvres are usually
      completed in a couple of seconds. The interval of time between the absorption of
      light quanta by the photoreceptors and the generation of an appropriate
      behavioural response is very short, encompassing only a few tens of milliseconds.
      In this time the visual nervous system has abstracted the essential features of
      the object, and recognized it (where appropriate), or measured its movement and
      computed an interception course. As an elementary unit of computation, we know
      that a neuron in the nervous system is considerably slower than, say, a flip-flop
      in the CPU of a modern computer. However, it is evident from the visual
      performance of an insect that the nervous system as a whole processes optical
      information much faster than a modern computer does. Rapid processing of visual
      information by animals therefore has to be attributed to the structure and the
      modus operandi of the nervous system.

PMID- 8271506
TI  - The statocysts of molluscs.
AB  - This article presents a brief review of the morphology and physiology of
      molluscan statocysts. These sense organs provide the animals with information on
      orientation and, in some cases, velocity of movement. They vary in sophistication
      from rudimentary, to organs almost as complex as those found in higher
      vertebrates. The morphology of different types of statocysts is described as well
      as their afferent responses, efferent systems and pharmacology.

PMID- 8271507
TI  - Modality difference in the physiological properties and morphological
      characteristics of the trigeminal sensory neurons.
AB  - A-delta nociceptive neurons divided according to fast-conducting (n = 21) and
      slow-conducting (n = 13) types were found to be different in electrophysiology
      and morphology, while between warm temperature (n = 23) and warm temperature and
      touch (n = 38) neurons, and between touch (n = 26) and vibrotactile (n = 59)
      neurons their characteristics were found to be similar.

PMID- 8271508
TI  - Comparative physiology on excitation-contraction coupling.

PMID- 8271509
TI  - K+ accumulation around the giant axon of the squid: comparison of electrical and
      morphological measurements.
AB  - K+ clearance following axon activity was measured around squid axons and found to
      be 20 times more efficient in preparations that were undissected. Around
      dissected preparations, Schwann cells were found to be swollen and vacuolated. It
      is suggested that traditional dissection methods damage Schwann cells and their
      K+ clearance function is impaired.

PMID- 8271510
TI  - Saltatory conduction and a novel type of excitable fenestra in shrimp myelinated
      nerve fibers.
AB  - The findings of saltatory conduction in the invertebrate giant nerve fibers were
      mentioned, and the experiments for analyzing the mechanism of impulse conduction
      in the giant myelinated nerve fibers of Penaeus orientalis and Penaeus japonicus
      were reviewed. Saltatory conduction was also found in many middle- and small
      sized myelinated nerve fibers of, at least, 6 species of Penaeus shrimps.
      Saltatory conduction with its morphological basis in myelinated nerve fibers of
      vertebrates and invertebrates were compared, and it was concluded that the
      myelination of the nerve fibers in vertebrates and invertebrates has occurred
      independently.

PMID- 8271511
TI  - Effects of exogenous gangliosides on learning and memory in rats.
AB  - After 10 or more consecutive daily injections (I.P. 50 mg/kg for developing,
      adult and aged, 2.5 mg/mouse for neonatal) of total bovine gangliosides, rats
      were trained to perform the discrimination tasks. The results show that
      gangliosides can enhance the learning ability and memory retention in rats at
      different ages.

PMID- 8271512
TI  - Structure-function studies of voltage sensitivity of connexins, the family of gap
      junction forming proteins.

PMID- 8271513
TI  - Optical recording and information theoretic analysis of Aplysia gill-withdrawal
      reflex.
AB  - A new experimental setup has been devised to perform Aplysia optical recording,
      the firing of the siphon sensory neurons being precisely controlled. Significant
      crosscorrelations between the siphon sensory neurons and optically detected
      neurons were obtained by our information theory-based analysis, and we discussed
      possible roles of the detected neurons in the gill-withdrawal reflex.

PMID- 8271514
TI  - The ampullary electroreceptor as a pH sensor?

PMID- 8271515
TI  - Microsecond response of a voltage-sensitive merocyanine dye: fast voltage-clamp
      measurements on squid giant axon.
AB  - Extrinsic absorption changes exhibited by squid giant axons stained with the
      voltage-sensitive merocyanine-oxazolone dye NK 2367 were measured during brief
      voltage-clamp steps. Experiments that employed an optical recording system having
      a sub-microsecond response time constant demonstrate that this dye responds to
      step changes in membrane voltage in less than 2 microseconds at room temperature.
      The optical response is independent of ionic currents and is unlikely to depend
      upon cytoskeletal or cytoplasmic events.

PMID- 8271516
TI  - Propagation of excitation in the visual cortex studied by the optical recording.

PMID- 8271517
TI  - Spatiotemporal observation of guinea pig auditory cortex with optical recording.
AB  - The spatiotemporal characteristics of neural activity in the guinea pig auditory
      cortex were studied in order to clarify neural processing and coding mechanisms
      of complex sounds. We used a multi-channel optical recording system for a voltage
      sensitive dye: RH795. The experimental results showed that a boomerang-shaped
      moving pattern of optical response appeared on the cortical surface in response
      to complex sounds (clicks) stimulation, but a rather fixed pattern appeared in
      response to tone burst stimulation. The tonotopical organization observed using
      microelectrode was not directly visible, but a similar topographic pattern was
      evidenced by selecting regions of a strong response evoked by tone-bursts. The
      correlative functions of regionwide responses may indicate a parallel and serial
      neural processing structure.

PMID- 8271518
TI  - Measuring nerve excitation with polarized light.
AB  - There are changes in nerve birefringence and optical activity associated with
      nerve impulses. The birefringence response resembles the time integral of the
      gating current. Its magnitude suggests several hundred peptide bonds per channel
      reorient during excitation. The optical activity change has a different time
      course from the birefringence signal. Its amplitude is approximately consistent
      with the reorientation of alpha-helices within sodium channel molecules.

PMID- 8271519
TI  - Measurement of calcium release from the sarcoplasmic reticulum into the myoplasm
      of frog cut muscle fibers.
AB  - Ca release from the sarcoplasmic reticulum of frog cut muscle fibers has been
      estimated with two different methods. The first method is to measure the
      myoplasmic free [Ca] transient under nonperturbing conditions and then estimate
      the amounts of Ca that are bound to the myoplasmic buffers troponin and
      parvalbumin. The Ca released from the sarcoplasmic reticulum is estimated from
      the sum of the concentrations of free Ca and of Ca bound to the indicator, to
      troponin, and to parvalbumin. The second method is to estimate the amount of Ca
      release by capturing most of the Ca with a large concentration of a high affinity
      Ca buffer. Both methods give similar estimates of the amount of Ca release
      following a single action potential and of the shape and amplitude of the release
      waveform.

PMID- 8271520
TI  - Dendritic excitability in CNS neurons: insights from dynamic calcium and sodium
      imaging in single cells.
AB  - We measured changes in [Ca2+]i and [Na+]i in the dendrites of cerebellar Purkinje
      cells and hippocampal pyramidal cells using high speed imaging of the
      fluorescence changes of intracellularly injected fura-2 and SBFI. These
      transients were detected in synchrony with intracellular recordings of membrane
      potential. In this way rapid calcium or sodium transients could be associated
      with specific electrical events. Using this technique we could determine the
      spatial distribution and source of transients evoked either intrasomatically or
      synaptically and could relate them to electrically recorded sodium and calcium
      spikes.

PMID- 8271521
TI  - Confocal imaging of cAMP signals in Aplysia neurons.

PMID- 8271522
TI  - Inositol trisphosphate/Ca2+ as a major signal transduction pathway from
      bradykinin receptors.
AB  - Enzymatic phosphatidylinositol-4,5-bisphosphate breakdown is not Ca(2+)-dependent
      in NG108-15 cells and the bradykinin-induced response consisted of at least two
      distinct components in the hybrid cells. The initial signal transduction from
      bradykinin receptors to acetylcholine secretion is composed of the inositol-1,4,5
      trisphosphate-dependent Ca2+ pathway despite multiple pathways in the late phase.

PMID- 8271523
TI  - KRI-1314: an orally effective inhibitor of human renin.
AB  - Biochemical and pharmacological properties of KRI-1314, a newly synthesized, low
      molecular weight (M.W.: 690) renin inhibitor, were investigated in vitro and in
      vivo. The novel amino acid norstatine, which is shorter in chain length than the
      well-known statine, was incorporated into KRI-1314 as a tetrahedral transition
      state analogue for the Leu10-Val11 scissile peptide in the renin substrate. KRI
      1314 more strongly inhibited plasma renins from primates than those from dogs,
      rabbits, guinea pigs and rats. KRI-1314 competitively inhibited highly-purified
      human renin with a Ki value of 9.9 x 10(-10) M. KRI-1314 strongly inhibited the
      tissue renin-like activities of various organs from Japanese monkeys, with IC50
      values on the order of 10(-8) M. KRI-1314 was also very stable in various tissue
      homogenates from Japanese monkeys. Both intravenous (from 0.25 to 3 mg/kg) and
      oral (10 and 30 mg/kg) administration of KRI-1314 to anesthetized and conscious
      sodium-depleted Japanese monkeys, respectively, significantly lowered the blood
      pressure and plasma renin activity without affecting the heart rate. In Japanese
      monkeys, KRI-1314 was continuously detected in the plasma up to at least 7 hr
      after oral administration of 10 and 30 mg/kg. These results demonstrate that KRI
      1314 is a highly potent, primate-selective and long-lasting oral renin inhibitor
      with a blood pressure lowering effect.

PMID- 8271524
TI  - Effects of semotiadil fumarate, a novel calcium antagonist, on blood pressure and
      heart rate in conscious spontaneously hypertensive rats.
AB  - The acute antihypertensive effects of orally administered semotiadil, a novel
      calcium antagonist, were compared with those of nifedipine and diltiazem in
      conscious, unrestrained spontaneously hypertensive rats (SHRs). Semotiadil (10
      and 30 mg/kg) produced a dose-dependent hypotension that persisted for 18 hr at
      30 mg/kg. Diltiazem (30 and 100 mg/kg) and nifedipine (1 and 3 mg/kg) also
      exhibited hypotension dose-dependently, but their durations of actions were
      shorter than that of semotiadil. Semotiadil caused a slight increase in heart
      rate, while diltiazem and nifedipine caused a bradycardia and a marked
      tachycardia, respectively. These results suggest that semotiadil has a beneficial
      property as an antihypertensive drug.

PMID- 8271525
TI  - Protection against alpha-naphthylisothiocyanate-induced acute cholestasis in mice
      by a novel taurine conjugate of ursodeoxycholate (UR-906).
AB  - We investigated the effects of tauroursodeoxycholate (UR-906) and ursodeoxycholic
      acid (UDCA) on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis in mice.
      UR-906 and UDCA were given intravenously 2 hr prior to and 2 hr after ANIT (80
      mg/kg, p.o.) treatment. The animals were sacrificed 48 hr after ANIT
      administration, and serum markers of liver injury were examined. UR-906 prevented
      significant elevations in total bilirubin, bile acids and LDH. Furthermore, this
      drug reduced significant elevations in ALP and LAP. UDCA also prevented
      significant elevations in total bilirubin and LAP. These results indicate that UR
      906 as well as UDCA has a beneficial effect against ANIT-induced cholestasis in
      mice.

PMID- 8271526
TI  - Synergistic effects of cyclic AMP-related vasodilators and the phosphatase
      inhibitor okadaic acid.
AB  - The phosphatase inhibitor okadaic acid at 100 nM slowly but completely inhibited
      high K(+)-induced contraction in the rat aorta (t1/2 = 118.9 min). High K(+)
      induced contraction was partially inhibited (to 37-65%) by 1 microM forskolin,
      100 microM dibutyryl cyclic AMP, 100 nM atrial natriuretic peptide, 1 microM
      nitroglycerin, 10 nM sodium nitroprusside, 300 pM nicardipine or 100 nM
      verapamil. The rate of relaxation due to okadaic acid became faster when the
      contraction was partially inhibited by these compounds. Augmentation of the
      relaxation was greater with forskolin and dibutyryl cyclic AMP than with the
      other inhibitors. These results support the suggestion that okadaic acid inhibits
      phosphatase to augment the phosphorylation due to cyclic AMP-dependent kinase,
      resulting in smooth muscle relaxation.

PMID- 8271527
TI  - Inotropic effects of staurosporine, NA 0345 and H-7, protein kinase C inhibitors,
      on rabbit ventricular myocardium: selective inhibition of the positive inotropic
      effect mediated by alpha 1-adrenoceptors.
AB  - The influence of protein kinase C (PKC) inhibitors, staurosporine, NA 0345 and H
      7, on the alpha 1- and beta-adrenoceptor-mediated positive inotropic effect (PIE)
      was studied in rabbit ventricular myocardium. Staurosporine (1-10 nM), NA 0345
      (10-100 nM) and H-7 (1-10 microM) selectively attenuated the PIE mediated by
      alpha 1-adrenoceptors at concentrations that did not affect the beta-mediated PIE
      and basal force of contraction. Staurosporine at higher concentrations (> 10 nM)
      decreased the basal force, while NA 0345 and H-7 did not. In membrane fractions
      derived from rabbit ventricular muscle, neither staurosporine, NA 0345 nor H-7
      modified the specific [3H]prazosin binding at the concentrations that elicited
      the functional modulation. Accumulation of [3H]inositol monophosphate (IP1)
      induced by alpha 1-adrenoceptor stimulation was not affected by the PKC
      inhibitors. Phorbol 12,13-dibutyrate (PDBu), a PKC activator, also selectively
      attenuated the alpha 1-mediated PIE, but in association with the inhibition of
      the alpha 1-mediated IP1 accumulation. Staurosporine (1 nM), but not H-7,
      antagonized the PDBu-induced inhibitory action on the alpha 1-mediated PIE. These
      findings indicate that staurosporine, NA 0345 and H-7 produce a selective
      inhibition of the alpha 1-mediated PIE, probably through inhibition of the alpha
      1-adrenoceptor-mediated activation of PKC. On the contrary, externally
      administered phorbol ester may act by uncoupling of alpha 1-adrenoceptors to
      activation of phospholipase C through a pathway different from endogenous
      diacylglycerol to lead to a selective inhibition of the alpha 1-mediated PIE.

PMID- 8271528
TI  - The estrogenic and antiestrogenic activities of droloxifene in human breast
      cancers.
AB  - The effects of a new antiestrogen, droloxifene (DROL, (E)-alpha-[p-[2
      (dimethylamino)ethoxy]-phenyl]-alpha'-ethyl-3- stilbenol), on human breast cancer
      cells in vitro and in vivo were studied. Since phenol red has a binding affinity
      to the estrogen receptor (ER), we studied the activities of drugs in medium with
      or without this indicator. Estradiol-17 beta (E2) stimulated the growth of ER
      positive breast cancer cells, MCF-7, ZR-75-1 and T-47D, in medium without phenol
      red, but not in medium containing this indicator. In medium without phenol red,
      DROL had no marked effects on the growth of MCF-7 and ZR-75-1, but slightly
      stimulated the growth of T-47D. Tamoxifen (TAM) stimulated the growth of these 3
      cells. DROL dose-dependently inhibited the E2-induced stimulation of growth of
      these cells in medium without phenol red, but TAM inhibited the growth only at
      high concentrations. The growth of ER-negative breast cancer cells, MDA-MB-231,
      was not influenced by E2, DROL or TAM. DROL was more effective than TAM against
      ER-positive Br-10 breast carcinoma in nude mice, but neither drug had effects on
      ER-negative MX-1 breast carcinoma. These results suggest that DROL shows an
      antitumor effect on ER-positive breast cancers, being less estrogenic and more
      antiestrogenic than TAM.

PMID- 8271529
TI  - Effect of KRN2391, a novel vasodilator, on various experimental anginal models in
      rats.
AB  - The antianginal effect of KRN2391, N-cyano-N'-(2-nitroxyethyl)-3
      pyridinecarboximidamide monomethanesulfonate, on various anginal models in rats
      was compared with those of nifedipine and nicorandil. Angina pectoris was induced
      by methacholine or isoproterenol, and the change in the ST-segments in the
      electrocardiogram (ECG) was used as the parameter to indicate angina pectoris.
      The intracoronary administration of methacholine (3 micrograms) produced an
      elevation in the ST-segment of the ECG. This ST-elevation was inhibited by the
      intravenous administration of KRN2391 (30 and 100 micrograms/kg), nifedipine (100
      and 300 micrograms/kg) and nicorandil (1000 and 3000 micrograms/kg). The
      administration of isoproterenol (10 micrograms/kg/min, i.v.) produced a
      depression of the ST-segment of the ECG. The intravenous administration of
      KRN2391 (100 micrograms/kg), nifedipine (100 micrograms/kg) and nicorandil (3000
      micrograms/kg) inhibited the ECG changes induced by isoproterenol. These results
      suggest that KRN2391 exerts a potent protective effect on angina pectoris models
      compared with nifedipine and nicorandil. KRN2391 appears to be useful as an
      antianginal drug.

PMID- 8271530
TI  - Effect of NG-nitro-L-arginine on effective vascular stiffness in dogs.
AB  - It has been reported that there is a continuous release of nitric oxide (NO) that
      contributes to the regulation of vascular tone in the arterial system. In
      contrast, the role of NO on vascular tone in the venous system is controversial.
      We examined the effect of NG-nitro-L-arginine (LNNA), an NO synthase inhibitor,
      on venous tone in dogs. Venous tone was evaluated by effective vascular stiffness
      (EVS), which was calculated from the changes in central venous pressure recorded
      simultaneously with changes in blood volume. LNNA (10 mg/kg, i.v.) increased EVS
      from 0.21 +/- 0.04 to 0.30 +/- 0.03 mmHg.kg/ml as well as increasing the systemic
      vascular resistance. NG-Nitro-D-arginine had no effect on EVS. The LNNA-induced
      increase in EVS was partly reversed by L-arginine, but not by D-arginine,
      indicating that the increase in EVS was attributable to a blockade of NO
      synthesis. Since the present study was conducted under ganglion blockade,
      nitroxidergic nerve terminals do not seem to be the source of NO in this case.
      These findings suggest that NO (endothelium-derived relaxing factor) is
      constantly released in the venous system and contributes to the regulation of
      total systemic venous tone.

PMID- 8271531
TI  - Cypridina luciferin analog reduces the incidence of ischemia/reperfusion-induced
      ventricular fibrillation.
AB  - A Cypridina luciferin analog (CLA), considered to be a sensitive and specific
      agent for the assay of superoxide, was assessed in isolated hearts for its
      effects on ischemia/reperfusion injury. Hearts of anesthetized male Wistar rats
      were isolated and perfused with a modified Krebs-Henseleit bicarbonate buffer to
      serve as non-recirculating working heart preparations. After 15 min of perfusion
      to achieve stability, they underwent 20 min of global ischemia and were then
      reperfused for 30 min with or without 250 microM of CLA, dissolved in the
      perfusate. The incidence of ventricular fibrillation was only 13% in the CLA
      group, whereas it was 88% in the controls. The CLA treatment was further
      associated with significantly increased left ventricular developed pressure and
      cardiac output; and in contrast, the left ventricular end-diastolic pressure was
      significantly reduced, as compared with the control group. Thiobarbiturate
      reacting substance content in the hearts of the CLA group was significantly
      decreased (27.5 +/- 2.4 versus 36.9 +/- 9.7 mumol/g dry weight). This study thus
      indicates that CLA may be useful for alleviating ischemia/reperfusion injury
      (reperfusion-induced arrhythmia and damage to heart function) involving free
      radicals.

PMID- 8271532
TI  - Development of tolerance to morphine antinociception in mice treated with
      nociceptive stimulants.
AB  - We have examined whether or not the presence of pain can block the development of
      tolerance to morphine antinociception in mice. A single injection of formalin or
      Freund complete adjuvant into the dorsal part of one side of the hind paw
      resulted in a significant swelling of the treated paw which lasted more than 5
      days. In formalin-treated animals that received the initial morphine 2 hr after
      the stimulant, the development of tolerance to morphine was delayed without
      affecting morphine antinociception when the effect was measured daily by the tail
      pinch (TP) method but not by the tail-flick (TF) method. However, the stimulant
      suppressed tolerance development even in the TF method unless the daily
      measurement was undertaken. When morphine injection was started from 5 days after
      the formalin injection, tolerance developed in a pattern similar to that in the
      control animals. On the other hand, treatment with Freund adjuvant did not affect
      the development of tolerance measured by both the TP and TF methods, with or
      without daily measurement of antinociception. When acetic acid was used as a
      stimulant, daily morphine was administered before or after the acetic acid
      injection, in the presence or absence of pain, tolerance developed to the same
      extent as in the control group, regardless of the time of morphine injection.
      Thus, our results suggest that the development of tolerance to narcotics may be
      modified by various factors, such as the type and intensity of nociception; and
      they also suggest that different results may be produced depending on the test
      method.

PMID- 8271533
TI  - Effects of age and calcium ion on testis carbonyl reductase in rats.
AB  - To examine the role of carbonyl reductase (CR) in the development and function of
      testis, age-related changes in CR and the effect of exogenous calcium on CR in
      rat testis were studied. Testicular CR activity was the highest at 3 weeks of age
      when the enzyme activity was measured at 2, 3, 4, 8 and 20 weeks of age. The
      intensity of positive protein bands in testicular cytosol was similar among these
      age groups in Western blot analysis with anti-rat ovarian CR antibody. In 3-week
      old rats, intravenous administration of 4 mg/kg calcium markedly suppressed the
      activity to about 50% of the control level 1 min after the treatment.
      Pretreatment with nicardipine prevented the inhibitory effect of exogenous
      calcium on the testicular CR activity in 3-week-old rats, indicating that the
      suppressing action of calcium on the enzyme activity was mediated by the entry of
      extracellular calcium via calcium channels. There were no significant changes in
      the CR activity following the treatment with calcium and nicardipine in the other
      3 age groups examined. These findings suggest that testicular CR plays an
      important role in the functional development of the testis during the infantile
      period in rats.

PMID- 8271534
TI  - Spontaneous oscillations of cytoplasmic free calcium ion concentration in
      cultured smooth muscle cells from guinea pig ileum.
AB  - The cytoplasmic free calcium ion concentration ([Ca2+]i) of cultured guinea pig
      ileum longitudinal muscle cells loaded with a fluorescent [Ca2+]i indicator, fura
      2, was measured by digital ratio imaging microscopy. Spontaneous [Ca2+]i
      oscillations were observed in 25% to 80% of the cells, which differed with the
      batches of the cultured cells after 5 to 8 days in culture. The frequency and
      amplitude of the [Ca2+]i oscillations in each individual cell were usually
      regular, but heterogeneity between neighboring cells was observed. The
      spontaneous [Ca2+]i oscillations were also observed even after incubation of the
      cells under a serum-free condition for 72 hr. Exchange of extracellular solution
      to Ca(2+)-free solution containing EGTA or BAPTA immediately stopped the [Ca2+]i
      oscillations. The ratio of the oscillating cells was dependent on the
      extracellular calcium ion concentration ([Ca2+]o); and heterogeneity in the range
      of the [Ca2+]o to generate the [Ca2+]i oscillations was observed. An inorganic
      Ca(2+)-antagonist, LaCl3, immediately suppressed the [Ca2+]i oscillations, but
      the treatment with verapamil or nicardipine, Ca(2+)-channel blockers, did not
      have any effect on the [Ca2+]i oscillations. An inhibitor of the intracellular
      Ca2+ pump, thapsigargin, induced a transient increase in [Ca2+]i and then
      inhibited the spontaneous [Ca2+]i oscillations. Neomycin, a compound known to
      inhibit phosphoinositide turnover, inhibited the [Ca2+]i oscillations.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8271535
TI  - Thrombolytic activity of a novel modified tissue-type plasminogen activator,
      YM866, in a canine model of coronary artery thrombosis.
AB  - The thrombolytic activity of a novel modified t-PA, YM866, was compared with that
      of a recombinant t-PA in a canine model of copper coil-induced coronary
      thrombosis. The coronary thrombus was allowed to age for 1, 3 or 6 hr before
      either drug was administered. YM866 was administered by i.v. bolus injection,
      while t-PA was given by the same method, as well as by 60-min i.v. infusion.
      YM866 showed thrombolytic activity 2 to 4 times as potent as that of t-PA when
      administered by bolus injection, the difference in thrombolytic effect being
      obvious in the 3- and 6-hr-old thrombi. Coronary reperfusion was achieved more
      rapidly with YM866 than with i.v. infusion of t-PA. In animals injected with
      doses of more than 0.1 mg/kg of YM866, no acute reocclusion occurred. Depletion
      of plasma fibrinogen to 70% of baseline levels was observed in animals given 0.2
      mg/kg YM866, 0.4 mg/kg t-PA by bolus, and 0.6 mg/kg t-PA via infusion. The
      residual plasma YM866 and t-PA antigen 30 min after bolus injection was 25% and
      3% of the peak levels, respectively. YM866, administered by i.v. bolus injection,
      was thus confirmed to exert a thrombolytic effect superior to that of bolus
      injection and infusion of t-PA, without systemic fibrinolytic activation. These
      results suggest the potential clinical applicability of YM866 as a thrombolytic
      agent that can be administered by i.v. bolus injection for acute myocardial
      infarction.

PMID- 8271536
TI  - Histamine H2-receptor plays only a minor role in histamine-induced wheal response
      in the squirrel monkey and guinea pig.
AB  - We examined the contribution of the histamine H2-receptor to the histamine
      induced wheal response in squirrel monkeys and guinea pigs. Intradermal injection
      of histamine, 2-pyridylethylamine (a selective H1-agonist), and dimaprit (a
      selective H2-agonist) dose-dependently induced the wheal response in squirrel
      monkeys and guinea pigs, although the reaction to dimaprit was much weaker than
      that to the other agonists. Chlorpheniramine dose-dependently depressed the wheal
      response in squirrel monkeys and guinea pigs at doses of 0.03-1 mg/kg and 0.03-3
      mg/kg, p.o., respectively. However, famotidine, ranitidine and cimetidine had no
      effect at doses up to 30, 100 and 300 mg/kg, p.o. in guinea pigs and up to 1, 10
      and 400 mg/kg, p.o. in squirrel monkeys, respectively. Cimetidine (3-300 mg/kg,
      p.o.) dose-dependently potentiated the inhibitory effects of chlorpheniramine
      (0.1 mg/kg, p.o.) in guinea pigs, but had no effects in squirrel monkeys.
      Famotidine and ranitidine did not alter the response to chlorpheniramine in
      either animal. These results suggest that the histamine H2-receptor plays only a
      minor role in the histamine-induced wheal response in squirrel monkeys and guinea
      pigs.

PMID- 8271537
TI  - Epilepsies in infancy.

PMID- 8271538
TI  - Developmental and therapeutic pharmacology of antiepileptic drugs.

PMID- 8271540
TI  - Signal transduction mechanisms in epilepsy.

PMID- 8271539
TI  - Localizing value of seizure manifestations of temporal lobe epilepsies and the
      consequence of analyzing their sequential appearance.
AB  - We investigated the localizing and lateralizing value of principal seizure
      manifestations in temporal lobe epilepsies (signal symptoms, oroalimentary
      automatisms, somatomotor manifestations, unilateral dystonic posturing, ictal
      speech, motionless stare) of 223 complex partial seizures in 50 patients. All the
      patients had invasive long-term monitoring with the combined implantation of
      intracerebral electrodes in and subdural electrodes on the bilateral temporal
      lobes. Postoperative freedom from seizures was ascertained for longer than one
      year. We found that 35 patients had amygdalohippocampal seizures and 15 had
      lateral temporal seizures. The value of the manifestations was established in
      relation to the site and side of seizure origin and to the progression of seizure
      discharges within the unilateral temporal lobe or to the contralateral cerebral
      hemisphere. Several signs among the manifestations were found to be reliable in
      predicting the site or side of the temporal lobe seizure focus. We emphasized the
      importance of investigating sequential changes of seizure manifestations in
      relation to ictal EEG findings by means of simultaneous recording.

PMID- 8271541
TI  - Considerations in the classification of epilepsies and epileptic syndromes.

PMID- 8271542
TI  - Epileptic syndromes in neonates: nosological problems from etiological aspects.

PMID- 8271543
TI  - Early infantile epileptic syndromes with suppression-bursts: early myoclonic
      encephalopathy vs. Ohtahara syndrome.

PMID- 8271544
TI  - Epileptic encephalopathy associated with continuous spike-waves during sleep.

PMID- 8271545
TI  - Clinical and electroencephalographic study of unilateral or predominantly
      unilateral seizures.

PMID- 8271546
TI  - Drop attacks and epileptic syndromes.
AB  - 1. In addition to 4 types of drop attacks previously described by Ikeno et al.,
      we could ascertain the falls of the myoclonic-tonic type in genuine drop attacks.
      The genuine drop attacks were seen in Lennox-Gastaut syndrome, epilepsy with
      myoclonic-astatic seizures and other symptomatic generalized epilepsies, and
      never in partial epilepsies. 2. None of the patients with partial epilepsy
      revealed genuine drop attacks as defined. Their drop attacks were slower (i.e.
      the falls were completed in more than 1 sec.). 3. In the 15 patients with Lennox
      Gastaut syndrome, the drop attacks disappeared in 8 patients, and decreased in
      severity and frequency in 3 patients. Namely, the intractability of drop attacks
      in two-thirds of the children decreased as the patients grew older. This finding
      must be taken into consideration when patients with drop attacks are considered
      for surgical treatment of their epilepsy.

PMID- 8271547
TI  - An overview of progressive myoclonus epilepsy in Japan.

PMID- 8271548
TI  - Biological study on pathophysiology of epilepsy: secondary brain disorders
      following ictus.

PMID- 8271549
TI  - Alterations of receptors in the hippocampus of kindling rats: in vitro
      macroautoradiographic investigation.

PMID- 8271550
TI  - Seizure stage, persistence of kindled epileptogenesis, and mossy fiber sprouting.

PMID- 8271551
TI  - Experimental seizure-induced brain damage: electrophysiological, metabolic and
      pathological correlation.
AB  - Limbic seizures elicited by an intra-amygdaloid KA injection is the only and
      unique model which can produce unilateral hippocampal degenerative lesions and
      atrophy. This model is important not only to investigate neurophysiological
      epileptogenesis but also to study the causative process of human mesial temporal
      sclerosis observed in patients with intractable complex partial seizure.

PMID- 8271552
TI  - Temporal lobe epilepsy with extrahippocampal structural lesions.

PMID- 8271553
TI  - Local cerebral blood flow changes in the thalamus associated with human temporal
      lobe epilepsy.

PMID- 8271554
TI  - Clinical usefulness of SPECT for localizing epileptogenic foci in intractable
      partial epilepsy.

PMID- 8271555
TI  - Utility of quantitative assessment of regional cerebral blood flow with 123I-IMP
      SPECT: diffuse cerebral hypoperfusion in medicated epileptic patients.

PMID- 8271556
TI  - Surgical treatment of frontal lobe epilepsy: selection of operative procedures on
      the basis of seizure monitoring.

PMID- 8271557
TI  - Surgical treatment for pediatric epilepsy.

PMID- 8271558
TI  - Intractable temporal lobe epilepsy with calcified mass in the temporal lobe.

PMID- 8271559
TI  - Frontal lobe epilepsy with supplementary motor seizures successfully treated with
      cortical resection following intracranial EEG/CCTV monitoring and functional
      mapping.

PMID- 8271560
TI  - Tonic-automatism complex: cases with violent gestural automatisms following a
      brief tonic seizure.

PMID- 8271561
TI  - Subtemporal amygdalohippocampectomy for medically intractable temporal lobe
      epilepsy.

PMID- 8271562
TI  - Linkage analysis between familial myoclonus epilepsy and short arm of chromosome
      6 using HLA phenotype as genetic marker.

PMID- 8271563
TI  - Simultaneous VTR-surface EEG recordings of simple partial seizures of childhood
      onset.

PMID- 8271564
TI  - Periodic spasms: focal type and generalized type.

PMID- 8271565
TI  - Studies on chromosomal anomaly syndrome with epilepsy.

PMID- 8271566
TI  - Inhibition of self-induced photogenic seizures.

PMID- 8271567
TI  - Valproate retard granule: efficacy and side effects.

PMID- 8271568
TI  - Concentrations of zonisamide in serum, free fraction, mixed saliva and
      cerebrospinal fluid in epileptic children treated with monotherapy.

PMID- 8271569
TI  - Carbamazepine and carbamazepine-10, 11-epoxide concentrations in rat brain and
      blood evaluated by in vivo microdialysis.

PMID- 8271570
TI  - Side effects of phenytoin related to the xenobiotics metabolism by cytochrome P
      450-linked monooxygenase of liver microsomes in dark Agouti rats.

PMID- 8271571
TI  - Two epileptics showing antiepileptic drug-induced psychoses.

PMID- 8271572
TI  - Skin rash caused by carbamazepine.

PMID- 8271573
TI  - Longitudinal growth and endocrinological studies in childhood epilepsy on long
      term antiepileptic therapy.

PMID- 8271574
TI  - Induction of tonic spasms by carbamazepine: observations on 2 infants.

PMID- 8271575
TI  - Teratogenicity of antiepileptic drugs and drug specific malformations.

PMID- 8271576
TI  - A prospective follow-up of the offspring of epileptic patients.

PMID- 8271577
TI  - Classification of epilepsies and epileptic syndromes in young children.

PMID- 8271578
TI  - Studies of mitochondria DNA in progressive myoclonus epilepsy (PME) and a case of
      atypical MELAS.

PMID- 8271579
TI  - Transient anoxia induces seizure reappearance in rat brain slices bathed in
      magnesium-free medium.

PMID- 8271580
TI  - Epileptogenesis in perirhinal cortex in vitro.

PMID- 8271581
TI  - Estimation of electrical source generators of diffuse slow spike and wave complex
      in Lennox-Gastaut syndrome.

PMID- 8271582
TI  - Long-term follow-up of EEG foci in childhood partial epilepsy.

PMID- 8271583
TI  - Clinico-polysomnographical evolutions in benign epilepsy in childhood with centro
      temporal foci.

PMID- 8271584
TI  - Interhemispheric correlation analysis of EEGs before and after corpus
      callosotomy.

PMID- 8271585
TI  - Prospective study of postoperative seizure in intracranial meningioma.

PMID- 8271586
TI  - Evaluation of source generators in partial seizures: availability of
      neuroradiological images superimposed on the dipole tracing.

PMID- 8271587
TI  - Polysomnographical study in the patients of frontal lobe epilepsy with ictal
      automatism.

PMID- 8271588
TI  - Topographical mapping of P300 on epileptics.

PMID- 8271589
TI  - Disturbance of visual information processing in temporal lobe epilepsy: in
      comparison with idiopathic generalized epilepsy.

PMID- 8271590
TI  - Epilepsies of neonatal onset.

PMID- 8271591
TI  - A clinical study of seizures induced by hot bathing.

PMID- 8271592
TI  - Three cases of symptomatic infantile spasms closely related to the occipital
      epileptic discharges before their onset.

PMID- 8271593
TI  - Prognosis of childhood epilepsy after discontinuation of antiepileptic drug
      therapy.

PMID- 8271594
TI  - Retrospective study of single unprovoked seizure.

PMID- 8271595
TI  - Public attitudes toward epilepsy in Japan.

PMID- 8271596
TI  - Quality of life in schoolchildren and students with epilepsy: a survey by
      questionnaire for nurse-teachers in Shimane prefecture.

PMID- 8271597
TI  - Psychosocial problems in patients with seizure-free period more than 3 years: by
      using the WPSI.

PMID- 8271598
TI  - Effect of the laterality of interictal discharge and antiepileptic drugs on
      cognitive function in temporal lobe epilepsy: a preliminary study.

PMID- 8271599
TI  - The effect of phenytoin on voltage-dependent Na+ channels in epileptic El mice.

PMID- 8271600
TI  - Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels
      in vivo, and carbamazepine does not antagonize adenosine effect in vitro:
      mechanisms of blockade of seizure spread.

PMID- 8271601
TI  - Antiepileptic effects of allopurinol involved in hippocampal specific SOD
      (superoxide dismutase) induction in the mutant El mouse.

PMID- 8271602
TI  - Effects of opioid antagonists on hypoalgesia in seizure-susceptible El mouse.

PMID- 8271603
TI  - The effect of seizures on protein synthesis in El mouse brain.

PMID- 8271604
TI  - Suppression of kindled seizures after bilateral injection of 3-(2
      carboxypiperazine-4-yl) propyl-1-phosphonic acid into the striatum in amygdaloid
      kindled rats.

PMID- 8271605
TI  - Mossy fiber sprouting in amygdala and perforant path kindled rats.

PMID- 8271606
TI  - Changes of pertussis toxin-catalyzed ADP-ribosylation involved in the long
      lasting epileptogenesis in the kindling model.

PMID- 8271607
TI  - Changes of guanidino compounds in the hippocampal kindled rat brain.

PMID- 8271608
TI  - Effect of pentylentetrazol (PTZ) kindling on GABAergic system: a histochemical
      study by staining for GABA-transaminase (GABA-T).

PMID- 8271609
TI  - Anticonvulsant effect of topiramate [2,3:4,5-bis-O-(1-methylethylidene-beta-D
      fructopyranose sulfate] on amygdaloid kindled seizures in the cat.

PMID- 8271610
TI  - A new chronic model of spontaneous nonconvulsive generalized seizures.

PMID- 8271611
TI  - A histochemical study on surgically resected hippocampal tissue of patients with
      temporal lobe epilepsy.

PMID- 8271612
TI  - Correlations between local cerebral glucose utilization and electroclinical
      changes in rats by a kainic acid microinjection into a unilateral sensorimotor
      cortex.

PMID- 8271613
TI  - Changes of extracellular GABA concentrations in the ventral hippocampus during
      kainate-induced seizures in rats.

PMID- 8271614
TI  - Magnetic resonance imaging in status epilepticus elicited by kainate in rats.

PMID- 8271615
TI  - The susceptibility of pentylenetetrazole-induced seizure in rats with hippocampal
      lesion induced by trimethyltin.

PMID- 8271616
TI  - GTP binding proteins in postmortem human brain.

PMID- 8271617
TI  - Acute immobilization stress reduces (+/-) DOI induced 5-HT2-mediated head shakes
      in rats.

PMID- 8271618
TI  - Effect of some neonatal treatments on the hypothalamic-pituitary-adrenocortical
      function.

PMID- 8271619
TI  - Effects of electroconvulsive shock on the serotonin metabolism and serotonin1A
      receptors in the rat brain.

PMID- 8271620
TI  - The potentiation of serotonergic activity reduces conditioned fear-induced
      freezing behavior.

PMID- 8271621
TI  - Intracellular calcium concentration in C6BU-1 rat glioma cells: a single cell
      study using fluorescence microscopy/video imaging system.

PMID- 8271622
TI  - Iprindole treatment increases extracellular concentrations of NA nd DA in the
      medial prefrontal cortex: evidence that iprindole increases availability of
      synaptic catecholamine in vivo.

PMID- 8271623
TI  - Phosphoproteins involved in the mode of action of antidepressants and
      electroconvulsive shock: a possible role of cytoskeletal proteins.

PMID- 8271624
TI  - Hypothalamic MHPG measured by microdialysis in rats with PNMT inhibitors.

PMID- 8271625
TI  - Dysregulation of striato-nigral GABAergic pathway by chronic haloperidol
      treatment: the role of dopamine D1 receptor in the substantia nigra pars
      reticulata on the development of tardive dyskinesia.

PMID- 8271626
TI  - A follow-up study of adolescents with sleep-wake rhythm disorders.

PMID- 8271627
TI  - Long-term follow-up study of a school refuser with non-24-hour sleep-wake rhythm.

PMID- 8271628
TI  - Successful combined treatment with vitamin B12 and bright artificial light of one
      case with delayed sleep phase syndrome.

PMID- 8271629
TI  - A clinical diagnosis of the patients with sleep-wake rhythm disorders according
      to DSM-IIIR.

PMID- 8271630
TI  - Characteristics of sleep parameters of sleep logs on the circadian rhythm sleep
      disorders.

PMID- 8271631
TI  - Clinical study of sleep-wake disturbance in demented patients.

PMID- 8271632
TI  - Clinical EEG study of biological rhythm on manic state and remission state in MDI
      case (compared to monopolar depression case).

PMID- 8271633
TI  - A case of late onset rapid cycling affective disorder: changes in sleep pattern
      and rectal temperature in manic and depressive states.

PMID- 8271634
TI  - Method of analysis of temperature rhythm in depression and normal control--least
      squares method using plural cycles.

PMID- 8271635
TI  - Polysomnography and chronobiologic study on periodic hypersomnia.

PMID- 8271636
TI  - REM-NREM cycle length of narcoleptic subjects living in temporal isolation.

PMID- 8271637
TI  - Disturbances of sleep and waking in handicapped children (I): prolongation of
      apparent total sleep time in mental retardation.

PMID- 8271638
TI  - Disturbances of sleep and waking in handicapped children (II): Trend of circadian
      rhythm disorders in deaf children.

PMID- 8271639
TI  - Melatonin rhythms in irregular shift workers.

PMID- 8271640
TI  - Illuminance or brightness? Which factor plays the major role in the change of
      mood and rhythm?

PMID- 8271641
TI  - Long-term course of seasonal affective disorders: a preliminary report.

PMID- 8271642
TI  - Season and mania.

PMID- 8271643
TI  - Multicenter study on SAD in Japan: the 4th year report.

PMID- 8271644
TI  - Effects of menstrual cycle on plasma melatonin level and sleep characteristics.

PMID- 8271645
TI  - Effects of ultradian variation on smoking behavior.

PMID- 8271646
TI  - Wrist activity in morning and evening types.

PMID- 8271647
TI  - Changes of rectal temperature and wrist activity during 25-h sliding shift: a
      preliminary study.

PMID- 8271648
TI  - Stress-induced phase-shifts in the locomotor activity rhythm and increases in
      noradrenaline turnover in the locus coeruleus region.

PMID- 8271649
TI  - Estrous cycle related variation of blood pressure and heart rate in the female
      rat.

PMID- 8271650
TI  - Effects of vitamin B12 (mecobalamin) on the sensitivity of rat circadian
      behavioral rhythm to light.

PMID- 8271651
TI  - [Effect of Ca-antagonists on pulmonary blood flow during single-lung ventilation
      in the dog].
AB  - Experiments were conducted in 21 adult mongrel dogs to clarify the effects of Ca
      antagonist (nifedipine sublingual administration 2.5 mg or 5 mg, or nicardipine
      intravenous administration 30 micrograms/kg or 60 micrograms/kg) on pulmonary
      blood flow under the condition of collapsed lung on the side of thoracotomy.
      Under anesthesia, an endotracheal tube with a movable blocker was used to
      intubate the trachea and the thoracotomized lung was collapsed. Subsequently, a
      Ca-antagonist was given and the ratio of the left main pulmonary artery/ascending
      thoracic aorta blood flow was used as an index of hypoxic pulmonary
      vasoconstriction (HPV). The following results were obtained. 1. Ca-antagonist
      administration under lung-collapse on the thoracotomy side resulted in inhibition
      of HPV of the collapsed lung, whereas, arterial blood oxygen tension (PaO2)
      remained in the acceptable range. 2. The maintenance of the lowered PaO2 within
      the acceptable range may have been due to the increase in cardiac output and the
      elevation of mixed venous blood oxygen tension resulting from Ca-antagonist
      administration, as well as the residual HPV even after administration of the Ca
      antagonist.

PMID- 8271652
TI  - [Thyroid hormones in patients with clinical stable pneumoconiosis].
AB  - It is well established that alterations of serum thyroid indices frequently occur
      in nonthyroid disease. The most common finding is a reduced serum T3
      concentration in systemic illness, termed low T3 syndrome. It is considered that
      this syndrome is a beneficial adaptation to severe illness and reflects the
      duration and severity of illness. We measured serum thyroid hormones, pulmonary
      functions, and arterial blood gases in 245 patients (mean: 67.0 years) with
      clinical stable pneumoconiosis, and investigated the relations of thyroid
      hormones and other measurements. We also investigated the relation of thyroid
      hormones and radiographic findings. 1) There was a significant correlation
      between serum level of free T3 and %VC (p < 0.05), and between serum level of
      free T3 and FEV1.0 (p < 0.01). 2) There was no apparent correlation between serum
      level of free T3 and other pulmonary functions (V25/HT, FEV1.0%). 3) There was no
      apparent correlation between serum level of free T3 and blood gases (PaO2, PaCO2
      and A-aDO2). 4) There was no apparent correlation between serum level of free T3
      and radiographic findings. 5) Serum levels of free T4 and T4 showed no apparent
      correlations with other parameters. These results suggest that serum level of
      free T3 can be helpful to evaluate the clinical severity in patients with
      pneumoconiosis.

PMID- 8271653
TI  - [Changes in right ventricular hemodynamic function by unilateral pulmonary
      arterial occlusion test].
AB  - We performed unilateral pulmonary arterial occlusion test (UPAO) for the
      preoperative evaluation of lung function in patients undergoing lung resection.
      In this test, the main pulmonary artery of either side is occluded to simulate
      postoperative functional status. In order to evaluate the right ventricular
      hemodynamic function, we measured right ventricular ejection fraction (RVEF) and
      right ventricular end-diastolic volume index (RVEDVI) throughout UPAO by
      thermodilution method. We investigated the relationships between changes in right
      ventricular hemodynamic function and postoperative complications related to
      cardiac functions, namely arrhythmias or heart failure. Thirty-four patients
      without heart disease prior to lung resection were examined by UPAO, and RVEF and
      RVEDVI were measured. Analyses demonstrated that changes in RVEF were inversely
      correlated with changes in RVEDVI. In 6 cases, RVEDVI increased from control by
      over 20% during UPAO. All of these patients had postoperative cardiac
      complications. The hypothetical ventricular function curves showed a large
      increase in RVEDVI relative to right ventricular stroke work index (RVSWI),
      suggesting a decrease in right ventricular function. In conclusion, these results
      suggest that changes in RVEDVI during UPAO may predict postoperative cardiac
      complications in patients undergoing pulmonary resection.

PMID- 8271654
TI  - [Serum level of Pseudomonas aeruginosa-specific IgA in patients with chronic
      lower respiratory tract infection and its clinical significance].
AB  - Elevation of the serum IgA level has been observed in many cases of chronic lower
      respiratory tract infection. To determine the specificity of elevated serum IgA
      for the pathogen colonizing the respiratory tract of patients, we measured
      Pseudomonas aeruginosa-specific IgA titers in patients with chronic lower
      respiratory tract infections by ELISA. Sonicated P. aeruginosa strain BB5746 was
      used as the coating antigen. Optical density was significantly elevated in sera
      from patients in whom P. aeruginosa was consistently isolated from sputum
      cultures, when they were respondent to the antigen, indicating that bacteria
      specific IgA is not localized in the respiratory tract surface, but is
      circulating in the blood stream of these patients. The other two groups, chronic
      bronchitis patients from whom bacteria other than P. aeruginosa were occasionally
      isolated from sputum culture, and IgA nephropathy patients, had no detectable
      specific IgA in their sera as is the case in normal adults. Our results indicate
      that bacteria-specific serum IgA levels appeared to correlate with duration from
      the time of bacterial colonization with P. aeruginosa and the degree of bronchial
      and alveolar destruction seen on chest X-rays. In addition, detection of
      increased serum P. aeruginosa-specific IgA seems to contribute to the recognition
      of persistent bacterial colonization of the respiratory tract.

PMID- 8271655
TI  - [High dose steroid inhalation therapy using a large spacer: laboratory and
      clinical study on usefulness of the 4-puffs/inhalation method].
AB  - We investigated whether or not the inhalation method of beclomethasone
      dipropionate (BDP) influences patient compliance and the clinical effects of
      therapy in chronic bronchial asthma, together with a basic study on the lung
      deposition of BDP using a twin Impinger when various numbers of puffs were
      discharged into three different spacers (Volumatic, InspirEase, Aerochamber). It
      was clearly shown that only the spacer, Volumatic maintained a high deposition
      rate of BDP in the lung model with a dose of 4-puffs/inhalation. Eighteen chronic
      asthmatic patients were studied. The patients inhaled BDP (800-1600
      micrograms/day) by 1-puff/inhalation using a large spacer, Volumatic, for 12
      weeks, and they then inhaled the same dose of BDP as given in the previous period
      by 4-puffs/inhalation using the spacer for 16 weeks. We compared the compliance
      of BDP, attack score, %PEFR and frequency of beta-agonist inhalation between
      these two periods. The compliance of BDP was markedly improved after changing
      from 1-puff/inhalation (92.8%) to 4-puffs/inhalation (99.8%). In the 4
      puffs/inhalation period, attack score and %PEFR were significantly improved as
      compared to the 1-puff/inhalation period. The frequency of beta-agonist
      inhalation use in the 4-puffs/inhalation period was significantly lower than that
      in the 1-puff/inhalation period. These results indicate that when high dose
      steroid inhalation is given with a large spacer in chronic asthmatic patients, we
      should advice them of the appropriate inhalation method in order to obtain good
      compliance and clinical effects.

PMID- 8271656
TI  - [Proton magnetic resonance spectroscopy (1H-MRS) of peripheral blood lymphocytes
      in patients with sarcoidosis and interstitial pneumonitis].
AB  - We recently developed a method of proton magnetic resonance spectroscopy (1H-MRS)
      to measure the 1H-MR spectra of peripheral blood lymphocytes (PBL) using only
      10(7) cells. We investigated the clinical feasibility of this method for
      evaluating disease activities in sarcoidosis and interstitial pneumonitis. PBL
      was separated from 10 ml of venous blood by differential centrifugation with
      Ficoll-Conray. Using a 90 MHz MR spectrometer (EX90, JEOL), the spectrum was
      obtained with 4000 times accumulation of 1H signals by single 70 degree pulses at
      37 degrees C under spinning. Water signal was suppressed with the homo-gated
      decoupling sequence. The spectra were analyzed with Gaussian curve fitting. The
      spectra of patients with active disease showed significant increases in peak
      heights for (CH2)n and CH3 peaks compared with the control. The peak heights
      decreased after improvement of disease states. The changes in 1H-MR spectra
      suggested activation of PBL in patients with sarcoidosis and interstitial
      pneumonitis, since similar changes have been shown for cells activated with
      mitogens. Our preliminary results indicate that 1H-MRS may be useful to evaluate
      activation of PBL in sarcoidosis and interstitial pneumonitis.

PMID- 8271657
TI  - [Clinical effects of low-dose and long-term erythromycin in diffuse
      panbronchiolitis with chronic respiratory failure].
AB  - We studied the effects of erythromycin (EM) in diffuse panbronchiolitis (DPB)
      with chronic respiratory failure. Seventeen patients with DPB or sinobronchial
      syndrome receiving home oxygen therapy (HOT) were treated with EM of 400-600
      mg/day for twelve months. Five patients discontinued HOT, and hypoxemia was
      improved in five other patients. Clinical effects were evident at one month after
      the start of EM administration, and a stable state was achieved after six months
      of EM therapy. FEV1 was significantly increased in pulmonary function tests.
      Factors which influenced the effects of EM included the period between onset of
      clinical symptoms and commencement of HOT and/or between commencement of HOT and
      administration of EM. EM was effective for patients with obstructive, but not
      constrictive impairment in pulmonary function tests. These findings indicate that
      EM is effective for DPB even in patients with chronic respiratory failure.

PMID- 8271658
TI  - [Clinical evaluation of diagnosis and treatment in three cases of primary
      pulmonary cryptococcosis].
AB  - Pulmonary cryptococcosis has been considered as a disease associated with
      depressed immune function of the host. However, it may develop in healthy
      individuals without any underlying disease. Recently, we experienced three cases
      of primary pulmonary cryptococcosis. Case 1. A 30-year-old woman in the sixth
      week postpartum developed cough and low-grade fever. Chest X-ray showed
      infiltrative shadows in right S2 and left S6. A diagnosis of pulmonary
      cryptococcosis was made from transbronchial brushings and histological
      examination. Case 2. A 51-year-old man was noted to have abnormal shadows on
      chest X-ray film at a regular medical checkup. Chest X-ray examination showed a
      small nodular density in left S9. A diagnosis of pulmonary cryptococcosis was
      made from percutaneous pulmonary paracentesis. Case 3. A 58-year-old man was
      noted to have an abnormal shadow on chest X-ray film at a regular medical
      checkup. Chest X-ray examination showed a nodular density in right S8. A
      diagnosis of pulmonary cryptococcosis was made from transbronchial brushings and
      histological examination. All three cases showed no impairment in their immune
      functions. These cases are described with a discussion of the literature.

PMID- 8271659
TI  - [Contribution of K-channel and Na-K-ATPase to the relaxant responses of canine
      bronchial smooth muscle to various bronchodilators].
AB  - To determine whether activations of K-channel and Na-K-ATPase are involved in the
      action of bronchodilating agents, we studied the effects of various K-channel
      blockers and ouabain, a Na-K-ATPase inhibitor, on the relaxant responses of
      canine airway smooth muscle in vitro. Addition of charybdotoxin (ChTx), a Ca
      activated potassium channel blocker, and ouabain had no effect on the responses
      to verapamil and BRL 38227, but inhibited those to salbutamol, forskolin, DBcAMP,
      and nitroprusside. Apamin, a low-conductance K-channel blocker, and
      glibenclamide, an ATP-sensitive K-channel blocker, had no effect on the smooth
      muscle relaxation induced by any agents. The inhibitory effect of ChTx was
      predominant when the concentration of bronchodilator was low, whereas the effect
      of ouabain was observed in the presence of a high concentration of
      bronchodilator. These results suggest that Ca-activated K-channel and Na-K-ATPase
      may participate in the relaxation induced by bronchodilators that can raise
      intracellular cyclic nucleotides, and that the contribution of each component
      differs under different concentrations of the drugs.

PMID- 8271660
TI  - [Pulmonary tumor embolism: relationship between clinical manifestations and
      pathologic findings].
AB  - To elucidate the relationship between the clinical manifestations and pathologic
      findings in pulmonary tumor embolism, we reviewed the autopsy and clinical
      records of 318 patients who died of various cancers, excluding lung cancer. Sixty
      seven (21%) of the patients had at least one tumor embolus in the pulmonary
      arteries and 12 (3.8%) had multiple tumor emboli contributing to death. We
      considered that the 12 patients (6 with hepatoma, 3 with gastric cancer, and one
      each with colon cancer, pelvic cancer, and cervical cancer) had disease defined
      as pulmonary tumor embolism, and we fully analyzed these cases. Patients with
      hepatoma had manifestations of submassive pulmonary thromboembolism and patients
      with other cancers had manifestations of pulmonary microthromboembolism. The
      lungs of all of the 6 patients with hepatoma had both microscopic and macroscopic
      tumor emboli and 3 cases were accompanied by pulmonary infarction. On the other
      hand, the lungs of all of the remaining 6 patients had microscopic (including
      intracapillary) tumor emboli and 4 cases were accompanied by diffuse alveolar
      damage. The lung of 1 of the patients with hepatoma and 2 of the patients with
      other cancers also had pulmonary tumor thrombotic microangiopathy. In patients
      with hepatoma, the tumor emboli seemed to be derived from tumor invasion to large
      veins, while the tumor emboli seemed to be derived from widespread tumor invasion
      to lymphatic channels in the remaining patients. The authors conclude that
      pulmonary tumor embolism shows heterogeneous manifestations such as acute and
      subacute cor pulmonale and diffuse alveolar damage. Clinicians should keep in
      mind that the heterogeneity of the disease is closely associated with the
      varieties of malignancies and their spread.

PMID- 8271661
TI  - [Lung fibroblast growth-stimulating activity of serine protease].
AB  - We compared lung fibroblast growth-stimulating activity (FGA) of several serine
      proteases including thrombin in vitro, and examined the mechanism of FGA. FGA was
      measured by incorporation of 3H-thymidine into lung fibroblasts (IMR-90). The
      activities of the enzymes were measured by spectrofluorometric method with
      synthetic peptides specific for each enzyme, and these enzymes were added to the
      assay system for FGA at concentrations of 7 x 10(0)-7 x 10(5) unit/ml. Human
      thrombin, bovine trypsin and bovine alpha-chymotrypsin showed clear FGA, but that
      of alpha-chymotrypsin was lower than those of thrombin and trypsin. On the other
      hand, porcine pancreatic elastase and human neutrophil elastase did not show any
      FGA, and had a cytotoxic effect on fibroblasts. A specific low molecular-weight
      thrombin inhibitor, argatroban (MW. 562), inhibited not only the enzyme
      (peptidolytic) activity of thrombin, but also its FGA at the same concentration.
      These results suggest that serine proteases can be classified into at least two
      groups, showing FGA and cytotoxic activity, respectively, and that the FGA of the
      former group is mediated by their catalytic (enzymatic) action.

PMID- 8271662
TI  - [A case report of epithelioid hemangioendothelioma of the lung].
AB  - A 15-year-old woman presented with an abnormal chest X-ray taken at a medical
      check up. Her chest X-ray disclosed multiple nodular shadows in bilateral lung
      fields. A transbronchial biopsy was non-diagnostic and an open biopsy was
      performed. The tumor was histologically diagnosed as epithelioid
      hemangioendothelioma on the basis of associated with immunoreactivity to factor
      VIII related antigen by immunohistochemistry and the presence of Weibel-Pallade
      bodies on electron microscopy. She has been followed-up in her home town without
      significant change.

PMID- 8271663
TI  - [A case of sarcoidosis presenting as pulmonary nodules associated with pleural
      indentation fifteen years after onset].
AB  - A 65-year-old woman was admitted to our hospital because of pulmonary nodules,
      about 3 cm in diameter in the right upper lobe accompanied by pleural
      indentation, and 5 mm in diameter in the left middle lung field, revealed by
      chest X-ray. She had no clinical signs or symptoms except achalasia-like
      discomfort swallowing. Results of physical examinations were within normal
      limits. A specimen obtained from the nodule in right S2 by transbronchial biopsy
      showed noncaseating epithelioid granuloma containing asteroid bodies, and
      negative staining for acid-fast bacilli. No malignant cells were found in the
      specimen. Bacteriological examination of a bronchial lavage specimen was negative
      for pyogenic bacteria, mycobacteria and fungi. A PPD skin test was negative. BALF
      revealed an increase of lymphocytes and elevation of CD4/CD8 ratio. Fifteen years
      previously, the patient had been diagnosed as having sarcoidosis by scalene node
      biopsy, and had been treated with steroid therapy. Pulmonary nodules associated
      with pleural indentation in sarcoidosis is relatively rare, and is usually due to
      malignancy such as lung cancer. This possibility was ruled out clinically in the
      present case. Therefore, it was concluded that the pulmonary nodules in this case
      were due to the sarcoidosis itself.

PMID- 8271664
TI  - [A case of hypersensitivity pneumonitis induced by toluene diisocyanate
      presenting with transient bronchoconstriction].
AB  - A 50-year-old male spray paint worker was admitted with non-productive cough and
      dyspnea on exertion. Chest X-ray and chest CT showed diffuse interstitial shadows
      in the bilateral lung fields. After admission, the symptoms and chest X-ray
      findings improved over several days, and he was followed as an outpatient. He
      then developed nocturnal dyspnea with wheezing and dry cough every day. About two
      months later, chest X-ray showed more severe diffuse interstitial shadows which
      did not disappear after admission. Bronchoalveolar lavage and transbronchial lung
      biopsy revealed allergic exudative interstitial pneumonia, and he was treated
      with steroid therapy. Paint contains toluene diisocyanate, and challenge test to
      toluene diisocyanate was positive. In the early course, this case presented with
      bronchoconstriction; bronchial reversibility and bronchial hyperresponsiveness to
      methacholine were positive. Bronchoconstriction may cause worsening of
      respiratory symptoms in patients with hypersensitivity pneumonitis induced by
      isocyanates.

PMID- 8271665
TI  - [A case of chronic persistent cough caused by gastroesophageal reflux].
AB  - A 69-year-old female was admitted for the evaluation of chronic persistent cough
      of about six week duration which was particularly worse at night and did not
      respond to antibiotics or cough medicines. She did not smoke and had no history
      of allergies or abnormal inhalations. Eosinophil counts, serum IgE, CRP, titers
      of cold hemagglutinin (CHA), and antibody to mycoplasma were all within normal
      ranges. Chest X-ray films and respiratory function tests showed no abnormalities.
      Because of her complaint of mild heartburn, gastroesophageal reflux (GER) was
      thought to be a possible cause of her chronic cough. Upper gastrointestinal X-ray
      films revealed barium reflux up to the cervical esophagus, and gastrointestinal
      fiberoscopy showed reflux esophagitis. Bronchial biopsy specimens taken by
      fiberoptic bronchoscopy showed chronic inflammatory changes of bronchial mucosa
      with focal squamous metaplasia, mucosal basement membrane thickening, and
      lymphocytic infiltration in the submucosa. She made favorable progress following
      treatment with a histamine H2 blocker and cisapride for six weeks. She met
      Irwin's criteria and we concluded that her cough was caused by GER. We speculate
      that repeated tracheobronchial microaspirations of refluxed gastric acid may
      cause chronic inflammatory changes of the bronchial mucosa resulting in
      persistent cough.

PMID- 8271666
TI  - [A case of interferon-alpha-induced pneumonitis].
AB  - We report a case of interferon-alpha-induced pneumonitis. A 61-year-old man was
      diagnosed as having recurrence of renal cell carcinoma and treated with 3 x 10(6)
      unit of interferon-alpha daily for 8 weeks. On the 55th injection, he presented
      with a high fever and mild dyspnea, and his chest CT films revealed diffuse
      reticulonodular shadows in both lung fields. We suspected interstitial
      pneumonitis due to interferon-alpha, and started steroid therapy. He showed rapid
      improvement of symptoms and diffusing capacity, and the pulmonary infiltrates in
      his chest CT were markedly reduced. Transbronchial lung biopsy (TBLB) revealed
      slightly thickened alveolar walls and small granulomatous-like lesions. These
      granulomatous-like lesions showed marked accumulation of macrophages. To our
      knowledge, this is the first report of interferon-alpha-induced pulmonary injury
      in Japan.

PMID- 8271667
TI  - [Two cases of M. avium complex infection presenting as solitary pulmonary
      nodule].
AB  - Case 1 was a 75-year-old woman. Her chest X-ray showed a 3 cm solitary nodule in
      the right S4, and biopsy obtained by fiberoptic bronchoscopy revealed epithelioid
      cell granuloma. Four weeks later, Mycobacterium avium complex (MAC) was detected
      on culture of the bronchial lavage fluid. She was treated with INH, RFP and EB
      for 12 months and recovered with no relapse. Case 2 was a 75-year-old man with
      mild diabetes mellitus and hypertension. Chest X-ray showed a 4 cm solitary
      nodule in the right S9. Percutaneous pulmonary aspiration revealed numerous acid
      fast bacilli on smear, and he was treated with INH, RFP and EB. Culture proved M.
      avium complex. The patient was unable to continue his medications because of
      gastrointestinal side effects, so right lower lobectomy was performed. Cases of
      M. avium complex infection presenting as solitary pulmonary nodule are very rare.
      We found only 12 reported cases in Japan and in other countries. The most usual
      site of cavitary lesions in M. avium complex infections is both upper lobes, in
      contrast to the relatively even distribution of solitary pulmonary nodules of the
      14 cases (12 reported cases and our 2 cases).

PMID- 8271668
TI  - [A case of exogenous lipoid pneumonia probably due to domestic insecticide].
AB  - A 61-year-old female was admitted to our hospital because of cough, hemosputum
      and right chest pain. The P-A and L-R chest films revealed focal consolidation in
      the right upper filed and mass-like shadow in the right S3. Transbronchial lung
      biopsy specimens showed collections of lipid-laden macrophages. The lipid
      material of macrophages in broncholaveolar lavage fluid was stained yellow-orange
      with Sudan IV. The patient had no difficulty in swallowing and had no history of
      regular use of oily drugs. Fiberoptic bronchoscopy and chest CT showed no
      obstruction of bronchi. She had used much domestic insecticide with the doors
      closed before going to bed every summer and autumn for 10 years. We concluded
      that the domestic insecticide containing mineral oil had resulted in exogenous
      lipoid pneumonia. Her symptoms and abnormal shadows in chest X-ray film
      disappeared soon after antimicrobial chemotherapy was started. She is now healthy
      without recurrence.

PMID- 8271669
TI  - [A case of eosinophilic pneumonia due to tolfenamic acid].
AB  - We report a case of pneumonitis induced by tolfenamic acid. A 23-year-old woman
      was admitted to our hospital because of cough and fever. She had been treated
      with tolfenamic acid and other medications for lumbago. Nine days after the
      treatment, she developed erythema, fever, cough and dyspnea. Her chest X-ray
      revealed multiple patchy and micronodular shadows in both lung fields.
      Bronchoalveolar lavage fluid (BALF) showed increased total cells, lymphocytes,
      eosinophils and CD4/CD8 ratio. Microscopic examination of transbronchial lung
      biopsy (TBLB) specimens showed infiltration of mononuclear cells and eosinophils
      into the alveolar wall and the interstitium. After discontinuation of all drugs,
      her complaints, laboratory data and chest X-ray findings markedly improved. The
      lymphocyte stimulation test (LST) and challenge test for tolfenamic acid were
      positive. Based on these findings, we diagnosed this case as pneumonitis
      (eosinophilic pneumonia) due to tolfenamic acid. To our knowledge, there has been
      no reported case of pneumonitis due to this drug in Japan.

PMID- 8271670
TI  - [A case of pulmonary aspergilloma successfully treated with combination therapy
      of intracavitary injection of amphotericin B and intravenous administration of
      urinastatin].
AB  - A 57-year-old man with pulmonary tuberculosis underwent left upper lobectomy in
      1984. In 1987, chest X-ray showed a fungus ball, and Aspergillus species was
      isolated from sputum. He was treated by intracavitary injection of amphotericin B
      (AMPH) in June, 1992. However, no change was observed in the chest CT scan after
      a total dose of 1,000 mg of AMPH. Combination therapy of intravenous
      administration of 100,000 units of urinastatin and intracavitary injection of
      AMPH resulted in complete disappearance of the fungus ball on chest CT scan. This
      report describes case of pulmonary aspergilloma successfully treated with the
      combination of AMPH and urinastatin.

PMID- 8271671
TI  - [A case of severe interstitial pneumonia probably due to Chlamydia pneumoniae].
AB  - A 64-year-old male was admitted to our hospital with dyspnea and high fever. The
      patient had a relative bradycardia and severe hypoxemia. Velcr rales were heard
      throughout the entire lung fields. Leucocytosis was absent. Chest X-ray showed
      bilateral diffuse reticular shadows. Corticosteroid pulse therapy and minocycline
      were introduced on the suspicion of either idiopathic interstitial pneumonia or
      Chlamydial pneumonia. Subsequently, his symptoms gradually improved. Although the
      patient had no history of exposure to birds, the titer of complement fixation
      test for Chlamydia was 1:32 during the acute illness. Microplate
      immunofluorescence antibody technique proved infection with Chlamydia pneumoniae.
      We consider this is a rare case of severe pneumonia caused by C. pneumoniae.

PMID- 8271672
TI  - [A case of cervico-mediastinal tuberculous lymphadenitis].
AB  - A 27-year-old female presented to our hospital because of anterior chest pain and
      left cervical tumor. Her chest X-ray film showed bilateral swelling of the
      superior mediastinum, which was composed of multiple mediastinal masses with
      obliteration of adjacent mediastinal fat on chest CT film. A specimen obtained
      from a left cervical lymph node histologically showed granuloma formation with
      central caseous necrosis, and the diagnosis of cervicomediastinal tuberculous
      lymphadenitis was therefore made. Both cervical tumor and mediastinal masses
      decreased in size following antituberculous chemotherapy. Mediastinal tuberculous
      lymphadenitis in young adults is rare. It is difficult to differentiate this
      condition from other mediastinal tumors, although its CT findings are
      characteristic.

PMID- 8271673
TI  - [Constipation in childhood--from the pediatric viewpoint].
AB  - Chronic constipation is a common problem in paediatric practice. The majority of
      the toddlers can be successfully treated by conventional therapy. Young infants
      with constipation or older children with longstanding stool impaction with or
      without encopresis should be referred to a centre for further diagnostic and
      therapeutic management. Children with a paradoxical contraction of the external
      anal sphincter during attempted defecation on anorectal manometry profit form bio
      feedback-training by learning a normal defecation pattern.

PMID- 8271674
TI  - [Surgically treatable chronic constipative defecation disorders. Indications,
      diagnosis and therapy].
AB  - Paediatric surgeons are engaged in different causes of chronic constipation.
      Aganglionosis usually needs surgical therapy, but in dysganglionosis a distinct
      differentiation is necessary between patients sufficiently treated by
      conservative methods and others requiring surgery. Sometimes the operation seems
      to be an "ultima ratio" in these patients. Otherwise surgery can be necessary
      early in enterocolitis, ileus or toxic megacolon. In the spectrum of anal
      malformations constipation may be a primary symptom (anal ectopia, anal stenosis,
      low anal atresia with anocutaneous fistula) or appears as a post-operative
      complication (intermediate or high anal atresia). In secondary megacolon, surgery
      is performed to remove the result of therapeutic negation over many years. The
      operation may be the supposition to follow up with conservative treatment. In the
      management of constipated patients an exact diagnostic clarification has a
      central position. This especially includes anorectal manometry, x-ray examination
      with contrast medium application and defaecography and as last rectal biopsy.

PMID- 8271675
TI  - [Vitamin K for newborn infants: why and how?].
AB  - Several publications during the past 10-15 years report on the identification of
      acarboxyprothrombin (PIVKA II) in a varying proportion of examined newborn and
      babies (1.9 to 81.5%). These findings prove that the relevant infants were
      suffering from vitamin K deficiency. Hence, the researchers recommend to continue
      the prophylactic administration of Vitamin K to newborn. Another argument in
      favour of vitamin K prophylaxis is supplied by the results of epidemiological
      studies on the frequency of haemorrhages in newborn and babies caused by vitamin
      K deficiency. In respect of avoidance of haemorrhages, a single intramuscular
      injection of vitamin K appears to be the safest mode of application, but repeated
      peroral administration seems to be practically equally effective. The very
      frequently performed intramuscular injection of vitamin K is criticised not only
      because of possible local complications but also because of the greatly enhanced
      vitamin K concentrations in the blood after the injection. This enhanced
      concentration is accused of being responsible for the increased risk of malignant
      tumour growth in those babies who received vitamin K via the i.m. route, compared
      with the children who had not been given any injection or to whom vitamin K had
      been administered orally. For this reason vitamin K prophylaxis should be
      effected in newborn via the oral route (repeated administration), whereas the
      i.m. route should be an exception. Recommendations to this effect are already on
      record.

PMID- 8271676
TI  - [Judo in a training group for children with asthma].
AB  - 15 asthmatics of 7-14 years of age were trained in a special judo training group
      together with healthy children. The step-like training programme was composed in
      such a manner that an exercise-induced bronchospasm was kept as low as possible
      whereas the coordination, flexibility, physical and psychical resistance were
      improved. By means of adapted lung function tests the children were controlled,
      the aim was not so much to prove an improvement of functional values but rather
      to avoid injuries. Reactions confirmed by means of the sensitive flow-volume
      curve method did not present any clinical problems. Exercise-induced reactions
      occurred most frequently, if at all, after a warming-up phase and in the middle
      of the 14 training weeks. Both at the end of every lesson and at the end of the
      whole training course the number and internity of reactions decreased. Children
      suffering from exercise-induced asthma could be trained by means of judo sport
      without any problems. A combatant sport, such as judo, is particularly qualified
      for the improvement of motivation, coordination, dexterity and integration into
      the community of healthy children to increase self-confidence. Asthma sport
      groups are a medical and paedagogical necessity.

PMID- 8271677
TI  - [Genetics of bronchial asthma with reference to allergy].
AB  - No uniform opinion exists to date in respect of the transmission of a genetic
      disposition to asthma bronchiale and atopy. Literature references discuss both
      monogenic, autosomal dominant or recessive and multifactorial-polygenic heredity.
      The following contribution discusses the results of an own study on the
      occurrence of atopy and asthma bronchiale in 153 families. Multifactorial
      polygenic heredity with threshold value range is most suitable for the
      interpretation of our findings, even though an autosomal dominant heredity with
      reduced penetrance and variable expressivity might well be the basis for the
      transmission of a disposition to atopy and asthma bronchiale. In multifactorial
      polygenic heredity with threshold value range, empirical risk data are important
      for predicting the disease risk. Such data can be obtained only on the basis of
      extensive family research and apply only to the population for which they were
      obtained. The risk of occurrence of atopy or asthma bronchiale in families
      already affected by the increases, in our experience, with the number of the
      patients already suffering from the disease and with the closeness of
      relationship with the patients concerned. We found a recurrence risk for further
      children of 40-45% for atopy and of 5-10% for asthma bronchiale in those
      marriages where both one parent and already one child are suffering from the
      disease.

PMID- 8271678
TI  - [DNCG (acecromol) and ketotifen (Zatofug) in treatment of children with bronchial
      asthma].
AB  - In an open clinical study, 80 children and adolescents of 12 months to 20 years
      of age suffering from asthma bronchiale were treated for a minimum of 8 weeks
      with DNCG (acecromol) or ketotifen (Zatofug) or with both drugs. Both under the
      treatment with DNCG and with ketotifen the overall disease pattern was improved
      with a large proportion of the patients and the concurrent adjuvant medication
      with prednisolone and/or aminophyllin could be markedly reduced or in some cases
      discontinued altogether. Both substances appear to be comparable as far as the
      therapy result is concerned; however, the range of application of ketotifen is
      wider due to its additional antihistaminic action and oral administration, e.g.
      in case of concomitant urticaria or food allergy.

PMID- 8271679
TI  - [Echocardiography studies of children and adolescents with primary hypertension].
AB  - We evaluated 100 schoolboys and schoolgirls whose blood pressure levels were
      above the 90th percentile. To determine whether in childhood left ventricular
      hypertrophy can be induced by pressure overload, we measured the thickness of the
      interventricular septum and posterior wall of the left ventricle and calculated
      the left ventricular muscle mass. Compared with a normotensive control group the
      thickness of the septum and posterior wall was significantly higher in children
      with elevated blood pressure. The normal range of the wall thickness was not
      exceeded. Furthermore, the left ventricular muscle mass differs between the two
      groups. 13 per cent of the hypertensive children had a greater ventricular mass
      than two standard-deviations from the normotensive group. This signifies an
      adaptation to the haemodynamic effect on the increased blood pressure.

PMID- 8271680
TI  - [Atopic skeletal retardation as a possible cause for short stature and thoracic
      deformity in children with asthma].
AB  - Deformities of the chest occur not only in asthmatics suffering from severe
      attacks, but also in those having a mild form of the disease. It also occurs in
      children with atopic dermatitis and in members of atopic families without
      concomitant bronchial asthma. This observation and the fact that asthmatic
      children tend towards hyposomia, has prompted auxological investigations of
      asthmatic children. It was of interest to see whether asthma itself or the atopic
      disposition is responsible for disturbances of growth and development. The
      investigation was carried out as a cross-sectional study involving 173 asthmatic
      boys aged 1 1/2-18 years. The programme included among other things age, bone
      age, bone maturity difference (BMD: difference age minus bone age) height, type
      and severity of asthma (measured by means of scope of therapy). The rate of
      hyposomia (height < mean -2 SD) amounted in the whole group to 4.7 per cent. It
      rose in the extrinsic asthmatics to 6.6 per cent. This corresponds with a rise of
      two or three times the normal rate. 11.6 per cent of the probands showed a
      skeletal retardation of more than 2 years. The degree of BMD showed a significant
      dependence on age and type of asthma but not on the duration of the disease,
      severity or glucocorticoid therapy. Skeletal retardation cannot, therefore, be
      regarded as a direct consequence of bronchial asthma, whereas the significantly
      different averages of BMD in extrinsic and intrinsic asthmatics point to an
      atopic genesis, hence it might be possible to speak of an atopic retardation of
      the skeleton.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8271681
TI  - [Multiple abnormalities in a child with male karyotype due to familial partial Xp
      duplication].
AB  - A child with multiple abnormalities and intersexual external genitals is
      presented. The child has a male karyotype with a partial duplication Xp. Using
      additionally methods of molecular genetics the SRY-region was detected. We
      reviewed the only few persons described in the literature with male karyotype and
      partial duplications Xp. There are similarities in phenotype including sex
      inversion or intersexual genitals if the duplication is localised in the region
      Xp 21-->Xp 22. Whether these affected patients represent a new syndrome is a moot
      point. We also found the aberrant X-chromosome in the mother of the child. In the
      present pregnancy of the mother there is, therefore, a risk of recurrence.

PMID- 8271682
TI  - [Severe general symptoms after DPT vaccination--always a vaccination reaction or
      are there other explanations?].

PMID- 8271683
TI  - [Spastic hemiparesis after apoplexy in renal hypertension due to
      mesangioproliferative glomerulonephritis (with immunosuppressive treatment) and
      primary hypothyroidism--which vaccinations are permitted?].

PMID- 8271684
TI  - [Hydrocephalus internus with shunt system in meningomyelocele, generalized
      epilepsy, somatomotor and mental retardation and hemiplegia and recurrent urinary
      tract infections in neurogenic bladder--is BCG vaccination possible?].

PMID- 8271685
TI  - [How is preventive poliomyelitis vaccination of the child carried out when the
      mother suffers from Hodgkin's disease?].

PMID- 8271686
TI  - [Contralateral pneumothorax after lung surgery].
AB  - The results of 6 observations of contralateral pneumothorax are presented.

PMID- 8271687
TI  - [Specifics of endocrine regulation of digestion in patients with esophageal
      neoplasms after esophagogastroplasty].
AB  - In 67 patients with esophageal cancer, the peculiarities of endocrine regulation
      of alimentation after resection and plasty of the esophagus, using an
      isoperistaltic gastric tube were studied. Of these patients, 15 underwent
      correction of the disorders revealed. Accelerated evacuation of the content from
      a gastric transplant is accompanied by atony of the pylorus and is due to
      relative incompetence of neuroendocrine elements in gastric and duodenal mucosa
      (presence of a small amount of EC- and P-cells). Use of pentagastrin at the early
      postoperative period permits to accelerate the process of formation of the
      compensatory-adjusting mechanisms in the system of alimentation due to increase
      in functional activity of EC- and I-cells.

PMID- 8271688
TI  - [Lymphatic vessel and venous anastomosis in the treatment of patients with
      lymphedema].
AB  - Examination and surgical treatment of 31 patient with primary (17 cases) and
      secondary (14) lymphedema of an extremity at a stage of fibredema was carried
      out. It was established that a degree of increase in the volume of an extremity
      rather often didn't correspond to a stage of fibredema, pathological changes in
      the lymphatic vessels were pronounced to a different degree. However, this do not
      exclude possibility of their effective use for placing lymphoangiovenous
      anastomosis.

PMID- 8271689
TI  - [Surgical treatment of patients with pathologic flexure of the extracranial
      cerebral arteries].
AB  - The results of surgical treatment of 112 patients with pathologic tortuosity of
      the extracranial cerebral arteries have been analysed. Indications and choice of
      a method for operative intervention are substantiated. Arterial torsion and loop
      formation were the most severe types of deformity, which often caused impairement
      in the cerebral circulation.

PMID- 8271690
TI  - [Experience with the surgical treatment of aortic coarctation].
AB  - The initial experience with surgical treatment of aortic coarctation at the
      cardiosurgical centre in Donetsk has been summarized. Operated on were 24
      patients with hypoplasia of the proximal aorta. Waldhausen's isthmoplasty,
      placing of an end-to-end anastomosis, grafting of the aorta and creation of an
      oblique anastomosis were performed. Co-operation with therapeutics, pediatrics
      and neonatologists, as well as thorough examination of the patients, monitoring
      permit to achieve the results which are compatible to those of the large clinics.

PMID- 8271691
TI  - [Diagnosis and specifics of the clinical course of acute surgical sepsis].
AB  - The results of observations on 176 patients with sepsis are presented. Criteria
      for diagnosis of acute surgical sepsis are substantiated, it symptoms,
      peculiarities of the course and outcome described. The criteria for differential
      diagnosis of diffuse purulent peritonitis and peritoneal sepsis on the basis of a
      mechanism of the polyorganic failure syndrome development are presented.

PMID- 8271692
TI  - [Errors and complications in the treatment of patients with knife injury to the
      heart].
AB  - The results of treatment of 83 sufferers with knife injury to the heart have been
      analyzed. In 33.7%, the errors were made which caused death in 28.5% of the
      patients. Thorough analysis of the errors, efficient organization of work of the
      surgical in-patient department, advanced training of surgeons contributed to
      improvement of a result of treatment and reduction in lethality.

PMID- 8271693
TI  - [Helium-neon laser in the combined treatment of postoperative abdominal abscess].
AB  - The results of treatment of 116 patients with a residual abscess of the abdominal
      cavity, including 59 who underwent complex treatment with the use of a helium
      neon laser radiation, have been analysed. The use of intracavitary laser therapy
      in combination with active drainage of an abscess stimulated the reparative
      processes in the organism, permitted to improve the results of treatment, reduce
      lethality from 15.3 to 5.3% and mean duration of treatment--from 37.1 to 28.8
      days.

PMID- 8271694
TI  - [Multi-layer musculo-aponeurotic repair in the treatment of patients with
      extensive median abdominal hernia].
AB  - A modified method for hernioplasty consisting in performance of multi-layer
      reconstruction of the abdominal wall with transfer and implantation of one of the
      cuspids of the hernial sac tissues beyond the contralateral musculus rectus
      abdominis has been suggested. Operated on were 20 patients with extensive, or
      giant abdominal hernia. Within 2 years after the operation, no hernia recurrence
      was noted.

PMID- 8271695
TI  - [Surgical treatment of recurrent inguinal hernia].
AB  - The experience with surgical treatment of 89 patients with recurrent inguinal
      hernia is presented. A method for hernioplasty with the use of the pyramidal
      muscle transferred for covering the inguinal space is described. In 37 patients,
      no hernia recurrence and injury to the femoral vessels were revealed. This was
      indicative of the effectiveness of the method suggested.

PMID- 8271696
TI  - [Long-term results of surgical treatment of children with esophageal hiatal
      hernia].
AB  - The data on operative treatment of 16 children with esophageal hiatal hernia are
      presented. All the patients underwent plasty of the hiatus with the use of a
      thoracic approach according to the technique developed in the clinic. The results
      of treatment were studied within 1 to 15 years after the operation. In 15
      patients, a good result was noted, in 1--a satisfactory one.

PMID- 8271697
TI  - [Methods of treatment of end-stage hydronephrosis in children].
AB  - The results of operative treatment of 110 children with congenital hydronephrosis
      are presented. Conventional surgical treatment was ineffective in 38.5% of the
      patients. Complex investigation of a function of the kidney involved was
      performed with the use of computed renangiography. Development and use of
      segmental-selective resection of a kidney, pyelouretheral segment and renal
      pelvis permitted to decrease the incidence of unsatisfactory results more than 2
      fold.

PMID- 8271698
TI  - [Remote thermography in funnel-shaped chest deformity in children].
AB  - Examined were 47 children with a funnel-shaped chest deformity and 18 healthy
      children (control group) ranging in age from 2 to 14 years. Thermal fields of the
      chest and hands were registered. New data characterizing the degree of
      pronouncement of chest deformity and heart shift were obtained. In patients with
      bronchopulmonary diseases, the areas of hyperthermia corresponding to
      inflammatory process location were noted. Thermography of the hands permitted, to
      obtain the data characterizing the pronouncement of respiratory failure.

PMID- 8271699
TI  - [Iatrogenic effect of various therapeutic and diagnostic methods on a sick
      child].

PMID- 8271700
TI  - [Is it correct to call the surgical treatment of duodenal ulcer "stomach
      resection"?].

PMID- 8271701
TI  - [Deontologic aspects of outpatient consultation of the surgical patient].

PMID- 8271702
TI  - [Discussion interview in clinical training in surgery].

PMID- 8271703
TI  - [Diagnosis of perforative peritonitis in newborns].

PMID- 8271704
TI  - [Clinical aspects, diagnosis and surgical treatment of abdominal diseases in
      women].
AB  - The results of treatment of 31 women operated on for acute appendicitis are
      presented. At operation, a gynecologic disease was revealed in these women.
      Difficulty in differential diagnosis of acute appendicitis and gynecologic
      disease in a pregnant woman requires joint decision-making by a surgeon and
      gynecologist.

PMID- 8271705
TI  - [Hematocolpos, simulating kidney pelvic dystopia in a child].

PMID- 8271706
TI  - [Intestinal obstruction, caused by kidney cyst].

PMID- 8271707
TI  - [Diagnostic method in penetrating abdominal injury].

PMID- 8271708
TI  - [Wound retractor for operations on organs in the subhepatic fossa].

PMID- 8271709
TI  - [Intestinal probe].

PMID- 8271710
TI  - [Surgical repair of femoral hernia].

PMID- 8271711
TI  - [Hamartomatous polyposis (Peutz-Jeghers syndrome), complicated by small intestine
      invagination in a child].

PMID- 8271712
TI  - [A case of acute hemorrhagic pancreatitis, complicated by peritonitis in a
      child].

PMID- 8271713
TI  - [Isolated transverse rupture of the pancreas in a child].

PMID- 8271714
TI  - [Torsion of ovarian cyst with rupture and intraabdominal hemorrhage].

PMID- 8271715
TI  - [Calcinosis of the buttocks in a child after administration of magnesium sulphate
      solution].

PMID- 8271716
TI  - [Stab wound to the thigh penetrating into the abdominal cavity with injury of the
      small intestine in a child].

PMID- 8271717
TI  - [Cases of gunshot injury in children].

PMID- 8271718
TI  - [Treatment of a child with severe injury of the lower extremity complicated by
      hemorrhagic shock].

PMID- 8271719
TI  - [Cases of incarcerated internal hernia in children].

PMID- 8271720
TI  - [Combined multiple echinococcosis of the lung and liver in a child].

PMID- 8271721
TI  - [Phlegmon of the hernial sac after surgery for diffuse fibrinous peritonitis].

PMID- 8271722
TI  - [A case of diverticular esophageal duplication].

PMID- 8271723
TI  - [Profuse gastrointestinal hemorrhage combined with acute intestinal obstruction].

PMID- 8271724
TI  - [Bouveret syndrome].

PMID- 8271725
TI  - [Combined penetrating injury of the chest and abdomen].

PMID- 8271726
TI  - [Clinical value of lymphocyte adhesion inhibition test].
AB  - In patients with purulent inflammation, increase in adhesive capacity of the
      peripheric blood lymphocytes a degree being dependent on severity and spread of
      purulent inflammation, was revealed. The highest degree was noted in patients
      with generalized peritonitis, acute phlegmonous cholecystitis and destructive
      appendicitis.

PMID- 8271727
TI  - [A rare case of late two-stage splenic rupture].

PMID- 8271728
TI  - [A case of traumatic cyst of the greater omentum].

PMID- 8271729
TI  - [A case of fulminant acute appendicitis].

PMID- 8271730
TI  - [Incarceration of the uterine tube in inguinal hernia].

PMID- 8271731
TI  - [Abdominal syndrome in diabetes mellitus].

PMID- 8271732
TI  - [Papillary cancer of the thyroglossal duct].

PMID- 8271733
TI  - [Intravascular laser irradiation of the blood in the combined treatment of
      chronic suppurative lung diseases].
AB  - Intravascular laser irradiation of the blood (ILIB) in the complex of
      preoperative preparation was employed in 53 patients with chronic pulmonary
      disease. After performance of 5 ILIB procedures in patients, more rapid
      normalization of the indices of morphologic composition of gases and acid-base
      state of the blood, immunologic status of the organism, functions of external
      respiration was noted as compared to a control group. The incidence of
      postoperative complications reduced by 4%, duration of hospital stay shortened by
      8.1 days.

PMID- 8271734
TI  - [Stomach neoplasm in patients with gastric ulcer].
AB  - The authors analysed the course of the disease in 903 patients with gastric ulcer
      and in 406 cases of gastric carcinoma which developed in patients suffering from
      peptic ulcer. Among 345 patients who did not undergo operation, in 24 (7%)
      carcinoma occurred in the edge of the ulcer or in the cicatrix. Initial stages (I
      II) were revealed in 19 patients. Dysplasia of the mucous membrane was found in
      most patients 1-9 years before the occurrence of carcinoma. Patients with gastric
      ulcer belong to the risk group. The risk is highest in II and III degree
      dysplasia and atrophic gastritis. In III degree dysplasia surgical treatment must
      be considered.

PMID- 8271735
TI  - [Acute pancreatitis after gastric surgery].
AB  - After operation on the stomach in 1,602 patients (3.9% mortality) acute
      postoperative pancreatitis (APP) developed in 60 of them. Twenty patients died
      from APP. The impulsive pain symptom and diastasuria were characteristic of the
      clinical picture in 35 patients. According to the severity of the impulsive pain,
      the diastasis level in the urine, and the complex of therapeutic measures needed
      to arrest the developing APP, three degrees of ductal hypertension were
      distinguished. There were no deaths among patients with APP of the first degree.
      In 23 patients APP was marked by manifest intoxication from the first
      postoperative day and subsequent development of many complications which called
      for reoperations. In this group 18 patients died. In 2 cases APP was
      distinguished by a rapid course and fulgurant development. Attention was drawn
      from the very beginning to the extreme severity of the patients' condition.
      Symptoms of shock prevailed in the clinical picture. Both patients died. The
      authors suggest a scheme of APP prevention with the use of aldehydes,
      antioxidants, inhibitors of proteolytic enzymes, a complex of vitamins.

PMID- 8271736
TI  - [Hormonal changes shortly after surgery in patients operated for stomach ulcer].
AB  - The content of gastrin, pituitary thyrotropin hormone (TTH), the thyroid hormones
      thyroxin (T4) and triiodothyronine (T3), and 11-OCS in blood serum and the daily
      catecholamine content in urine were studied in 86 patients in the early periods,
      2-4 weeks, after resection of the stomach or selective proximal vagotomy (SPV).
      The content of gastrin, TTH, T4, and 11-OCS in blood was reduced and
      catecholamine excretion diminished in patients after gastric resection. After SPV
      the concentration of gastrin increased and that of TTH reduced. A certain
      relationship between the clinical course of peptic ulcer and the indices studied
      was revealed. The application of rehabilitation measures in the early periods
      after operations on the stomach improves the neuroendocrine regulation in the
      organism and the functional condition of the alimentary organs.

PMID- 8271737
TI  - [Surgical treatment of chronic duodenal ulcer complicated by extravasal
      compression of the celiac trunk].
AB  - The work analyses the results of examination and operative treatment of 69
      patients with chronic duodenal ulcer and concurrent extravasal compression of the
      celiac trunk. The clinical signs characteristic of this combination are
      distinguished and it is shown that these patients have low indices of maximal
      acid production with a high frequency of duodenal reflux. Decrease of the hepatic
      and gastric blood flow was also found. It is suggested that such patients should
      be treated by combination of selective proximal vagotomy and decompression of the
      celiac trunk which is accomplished by exposure of the aorta over the celiac trunk
      and retrograde division of the median diaphragmatic ligament. The late-term
      results of the operation were analysed for follow-up periods of up to 10 years.
      Poor results were recorded in 6.2% of cases.

PMID- 8271738
TI  - [Clinical course of asymptomatic cholecystolithiasis].
AB  - Gallbladder concrements were found in 6.7% of 30,000 persons over 40 years of age
      during dispensary screening. In 720 (2.4%) of them the clinical and laboratory
      findings corresponded to those in chronic calculous cholecystitis, whereas in
      1,290 persons gallbladder concrements were asymptomatic. Detailed study of 84
      records of patients with asymptomatic cholecystolithiasis made in possible to
      recognize in most of them also chronic inflammatory diseases and dyskinesia of
      the gastrointestinal tract which could be conducive to the formation of
      concrements. During a 4-year follow-up period, signs of chronic calculous
      cholecystitis appeared in only 6% of these patients. The authors conclude that
      most patients with asymptomatic cholecystolithiasis must be subjected to regular
      medical examination and only with the development of a clinical picture of
      chronic calculous cholecystitis only some of them should be treated by surgery.

PMID- 8271739
TI  - [Vagotomy in the treatment of duodenal ulcer and its complications].
AB  - The authors discuss the results of surgical treatment of 577 patients with
      duodenal ulcer and its complications by operations on the vagus nerve of an
      isolated character or together with operations on the stomach. The findings of
      dynamic endoscopic examination of healing of the ulcer in 250 patients are
      reported. The application of regional lymphostimulation in the prevention and
      treatment of postvagotomy gastroplegia and gastrostasis in more than 200 patients
      is described.

PMID- 8271740
TI  - [Differentiated treatment of generalized peritonitis].
AB  - The article discusses the results of treatment of 327 patients with generalized
      peritonitis in the toxic and terminal stages. The patients were divided
      conditionally into three groups. In the first group (42 patients) treatment
      consisted in routine cleansing of the abdominal cavity with drainage and
      introduction of antibiotics into it in the postoperative period. Mortality was
      45.7%, complications occurred in 52.6% of patients who had survived. In the
      second group (145 patients) peritoneal dialysis in the flow-drip regimen was
      applied 3 or 4 times per 24 hours in a volume of 3-4 liters. In this group
      mortality was 37.9%, the number of complications among the survivals was 41.1%.
      In the third group (140 patients) a complex of differentiated peritoneal therapy
      was employed, including the following developed methods: thorough intraoperative
      cleansing of the abdominal cavity with 10-15 liters of antiseptic solutions
      containing antibiotics chosen according to the results of express-bacterioscopy,
      "active" peritoneal dialysis in the flow-fraction regimen, as well as developed
      methods of laparostomy--controlled laparostomy, prolonged open administration
      with local cleansing and use of antibacterial ointments. With use of this
      complex, mortality reduced to 27.1% and the incidence of complications to 20.6%.

PMID- 8271741
TI  - [Various aspects of hormonal disorders in peritonitis].
AB  - Impairment of hemodynamics and metabolism, which is determined by the condition
      of the hypothalamo--hypophyseal-adrenal system, is very important in the
      pathogenesis of peritonitis. The cortisol content, the activity of plasma renin,
      aldosterone, T3 and T4 were studied in 50 patients with diffuse and generalized
      peritonitis. The regional control group was formed of 50 practically healthy
      individuals. The patients were examined on the 1st, 3rd, 7th, and 14th
      postoperative days. The "low T3" syndrome in considerable increase of the content
      of cortisol, which inhibits the production of triiodothyronine directly, was
      encountered during the entire postoperative period in patients with peritonitis.
      Hyporenin hyperaldosteronism occurred on the 7th-14th day, which was evidenced of
      distorted physiological mechanisms of the production of mineralocorticoids in
      peritonitis. The hormonal dysbalance in the examined patients was greatest of the
      7th postoperative day; the content of the studied hormones was partly normalized
      by the 14th day.

PMID- 8271742
TI  - [Thoracic approach for splenectomy in hematologic patients].
AB  - The article discusses the advantages of the thoracic approach in splenectomy in
      hematological patients. The high operative risk in patients with a marked
      hemorrhagic syndrome, and particularly, in the development of the Itsenko
      Cushing's syndrome, is emphasized. An abdominal approach fails to ensure a safe
      operation in these patients. By means of topographoanatomical studies, analysis
      of the postoperative complications, and detailed investigation of the operative
      stages the authors prove the advantages of approaching the spleen through the
      thorax with diaphragmotomy. From experience with 226 operations for splenectomy
      in various diseases of the blood system, the authors showed that the number of
      postoperative surgical complications may be reduced by several times as compared
      to that in an abdominal approach.

PMID- 8271743
TI  - [Duplex scanning of hemodynamic parameters of the celiac trunk and superior
      mesenteric artery in healthy volunteers].
AB  - The possibility of studying the hemodynamics in the visceral arteries of the
      abdominal aorta by duplex scanning was demonstrated. The results of examination
      of 30 healthy persons are discussed. Characteristic features of the blood flow
      spectrogram of the celiac trunk and superior mesenteric artery were revealed.
      According to the spectrogram, the flow of blood in the celiac trunk is
      characterized by rapidly increasing peak systolic rate and slowly diminishing
      diastolic rate to approximately 1/3 of the maximal value of systole. The
      character of the blood flow in the superior mesenteric artery is distinguished by
      a lesser peak systolic rate and the presence of a short-lived reverse rate before
      the sloping diastolic curve. Normal values of the blood flow volume rate were
      determined, it was 649 +/- 25.4 ml/min in the celiac trunk and 395 +/- 20.5
      ml/min in the superior mesenteric artery. Among the advantages of the duplex
      scanning method are noninvasiveness and safety and the possibility of dynamic
      study of the hemodynamic parameters.

PMID- 8271744
TI  - [Catheter dilatation in combined and generalized arterial occlusion and stenosis
      of pelvic and lower limb arteries].
AB  - The article discusses the possibilities and tactics of radiologically-guided
      intravascular angioplasty in extended and combined occlusive-stenotic lesions of
      the lower limb arteries from experience gained in 116 intravascular dilatations
      in 78 patients. The authors show that it is really possible to perform catheter
      angioplasty in patients with extended and combined occlusive-stenotic lesions of
      arteries of the pelvis and lower limbs with compulsory use of spasmolytic and
      anticoagulant therapy during the operation and, in addition, also disaggregate
      therapy in the postoperative period. Extended occlusions of the femoral artery,
      beginning from the opening of the deep femoral artery, should be managed by a
      retrograde popliteal approach.

PMID- 8271746
TI  - [Some remarks on the article A.A. Baulin et al. "Cholelithic intestinal
      obstruction"].

PMID- 8271745
TI  - [Effect of electrostimulation effect on the characteristics of nocturnal sleep].
AB  - The nature of night sleep was studied in oncogynecological patients 60 to 75
      years of age and in practically healthy females and males according to the
      findings of electroencephalography and electromyography of the forehead muscles.
      The EEG and EMG were recorded in a automatic regimen (EEG according to frequency
      and amplitude) every 3 seconds on a Datex computer, apparatus ABM. The
      examination was conducted in an isolated room. Patients with oncogynecological
      diseases were troubled by marked disorders of night sleep: they could not fall
      asleep for a long time, the first fast sleep occurred earlier than in healthy
      individuals, the desynchronization periods were more frequent than in healthy
      individuals. After a course of electrostimulation, daily for 40-60 minutes with
      an A-500-01 apparatus (high-frequency currents, modulated by low frequency,
      output 77 cyclec per sec. and 500 mA) the character of night sleep in
      oncogynecological patients improved noticeably both according to subjective
      evaluation and EEG and EMG characteristics. It is assumed that night sleep
      improves due to changed interrelation of the central nervous system mediators.
      The authors come to the conclusion that inclusion of a course of
      electrostimulation in preoperative management is expedient.

PMID- 8271747
TI  - [Prevention of complications in reconstructive surgery of burn injuries].
AB  - On the basis of treatment of more than 5,000 patients with postburn cicatricial
      contractures of the joints, deformities and defects of the soft tissues the
      authors studied the complications and their causes. Suppuration of the operative
      wounds, necrosis of grafts and the edges of the wound, and hematomas are the main
      complications. The character of the complications and their sequelae are
      connected directly with the specific features of the surgical intervention and
      type of plastics (free, flap, microsurgical, dermatotensia), as well as with the
      anatomical features of the tissues and vessels damaged by the burn, which reduce
      the resistance to infection and facilitate the appearance of circulatory
      disorders. Preventive measures are suggested which excluded purulent
      complications and reduced tissue necrosis to minimum. Therapeutic measures
      reducing sharply the sequelae of the complications are discussed. Preeminence of
      preventive measures over therapeutic measures is emphasized. Their timely
      application helps in attaining good outcomes of restorative and reconstructive
      operations in patients who had suffered from burns.

PMID- 8271748
TI  - [Prevention of postoperative deep vein thrombosis of the lower limbs].
AB  - Electrostimulation of the leg muscles during and after operative intervention is
      an effective method for the prevention of postoperative thrombosis of the deep
      veins of the lower limbs. It may be combined with electrostimulation of the
      gastrointestinal organs. Electrostimulation by means of the theta CH-1
      electrocardiostimulator in 18 patients with various intraabdominal interventions
      proved to be highly effective in the prevention of thrombosis of the deep veins
      of the lower limbs.

PMID- 8271749
TI  - [Methods of laparoscopy for patients in the early postoperative period].
AB  - The article describes in detail a method for laparoscopy in patients in the early
      periods after surgical intervention on the abdominal organs. Definite indications
      for endoscopic intraoperative laparostomy are pointed out, a bushing specially
      designed by the authors is described, and the terms and indications for dynamic
      visual examinations of the abdominal cavity are determined. The suggested method
      does not cause harm to the patient and allows early postoperative complications
      to be recognized in good time and the course of the inflammatory-reparative
      process in the zone of the operation to be appraised visually.

PMID- 8271750
TI  - [Radiologic localization of pancreatic insulinoma].
AB  - Thirty-one patients with insulinoma of the pancreas verified during operation
      were examined. The localization of the tumor was detected by ultrasonic
      examination in 9.7%, by X-ray computed tomography in 38.9%, by angiographic study
      in 32.1%, and by endoscopic retrograde pancreatocholangiography in 11.1% of
      cases. Complex use of the methods allowed the localization of the tumor to be
      determined in 48.4% of cases. The smallest diameter of insulinoma diagnosed
      during ultrasonic examination and endoscopic retrograde pancreatocholangiography
      was 1.5 cm, X-ray computed tomography and angiography demonstrated tumors
      measuring 1.0 cm in diameter. The diagnostic efficacy of the methods increases
      when the tumor is located in the body and tail of the pancreas. The examination
      scheme for patients with suspected insulinoma must include ultrasonic study and X
      ray computed tomography; when their results are negative angiography must be
      resorted to.

PMID- 8271751
TI  - [Treatment of chronic non-healing donor sites: transplantation of cultured human
      fibroblasts].
AB  - The authors discuss the first results of the use of cultivated human
      allofibroblasts in the treatment of persisting wounds of the donor areas in 13
      patients with deep burns and cicatricial deformities caused by the burns.
      Transplantation of cell cultures led to complete epithelialization of the wounds
      in 6-10 days. Complication, suppuration of the grafted material, was recorded in
      one case. Reaction of graft rejection was not encountered. The authors believe
      that the effect of the transplantation is due to stimulation of the
      epithelialization processes by the cultivated fibroblasts.

PMID- 8271752
TI  - [Verifying symptoms of peritoneal irritation in acute appendicitis].

PMID- 8271753
TI  - [Leiomyoma of the small intestine complicated by recurrent hemorrhage].

PMID- 8271754
TI  - [Gunshot injury of the pelvis].

PMID- 8271755
TI  - [Partial or total correction of pleural cavity volume after lung surgery].

PMID- 8271756
TI  - [Long-term prognosis in selective proximal vagotomy].

PMID- 8271757
TI  - [Hemoperfusion in acute poisoning].

PMID- 8271758
TI  - [Complications of blood purification procedures in intensive care patients].

PMID- 8271759
TI  - [Prevention and conservative therapy of acute kidney failure].

PMID- 8271760
TI  - [Principles and technology of therapeutic plasma exchange].

PMID- 8271761
TI  - [Plasmasorption].

PMID- 8271762
TI  - [Donor plasmapheresis].

PMID- 8271763
TI  - [Plasmapheresis in neurologic diseases].

PMID- 8271764
TI  - [Extracorporeal elimination treatment of autoimmune diseases].

PMID- 8271765
TI  - [Low density lipoprotein apheresis].

PMID- 8271766
TI  - [The therapy of hematologic-oncologic emergencies].

PMID- 8271767
TI  - [Hemodialysis and hemofiltration].

PMID- 8271768
TI  - [Continuous hemofiltration and other continuous blood purification procedures].

PMID- 8271769
TI  - [Pathophysiology of acute kidney failure].

PMID- 8271770
TI  - [Peritoneal dialysis].

PMID- 8271771
TI  - [Vascular access, anticoagulation].

PMID- 8271772
TI  - [Prevention and therapy of acute kidney failure in heart surgery and following
      trauma].

PMID- 8271773
TI  - [Kidney failure and detoxification in septic abdominal diseases].

PMID- 8271774
TI  - [Surgical procedures for the elimination of endotoxins].

PMID- 8271775
TI  - [The feasibility of solutions with adequate fluid exchange in hemofiltration].

PMID- 8271776
TI  - [Differential indications for detoxification procedures in intensive care].

PMID- 8271777
TI  - Interpretation of methamphetamine and amphetamine enantiomer data.
AB  - Interpretation of drug testing results is a challenging and complex task,
      particularly when the interpretation can result in establishing legitimate use of
      a drug or illicit use with all of its attendant complications (i.e., loss of job,
      criminal prosecution, etc.). One of the more challenging drugs to interpret is
      methamphetamine. While methamphetamine is a schedule II controlled substance, the
      l-enantiomer of methamphetamine is found in the Vick's Inhaler, which is a
      product exempted from control. For this reason, while identification of
      methamphetamine and amphetamine in the urine of an individual can clearly
      establish the use of methamphetamine, it does not prove the use of a controlled
      substance. Use of racemic methamphetamine can make the interpretation even more
      difficult because of the different metabolism and excretion of l- and d
      methamphetamine. Enantiomeric characterization of methamphetamine may not give
      unequivocal results. Evaluation of experimentally derived and published data from
      urine samples containing l- and d,l-methamphetamine indicates that use of the
      enantiomeric distribution of amphetamine affords unambiguous interpretation.
      Because the l-enantiomer is the only possible finding in an individual who is
      using the Vick's Inhaler, detection of the d-enantiomer or a mixture of the d-
      and l-enantiomers clearly establishes the use of a controlled substance. Without
      a prescription from appropriate medical personnel, this detection would indicate
      the illicit use of a controlled substance.

PMID- 8271778
TI  - Pharmacokinetics and pharmacodynamics of intranasal "snorted" heroin.
AB  - The purity of illicit heroin in the United States has increased steadily over the
      last several years, while prices have fallen. Associated with this trend, there
      has been a recent shift among heroin addicts from intravenous injection to
      intranasal use ("snorting"). Because of the lack of information on this route of
      administration, we evaluated the pharmacokinetic and pharmacodynamic properties
      of intranasal heroin. Results were compared to the effects of heroin by the
      intramuscular route. Six healthy, male volunteers were administered single doses
      of intranasal heroin hydrochloride (6 and 12 mg), intramuscular heroin
      hydrochloride (6 mg), and placebo. Blood levels of heroin, 6-acetylmorphine, and
      morphine were measured by gas chromatography/mass spectrometry. Simultaneous
      physiological, behavioral, and performance measures were obtained. Peak blood
      levels of heroin were attained within 5 min of heroin administration by the
      intranasal route, similar to those observed for intramuscular administration.
      Generally, the pharmacokinetic profile of intranasal heroin was equivalent to
      that for the intramuscular route. Physiological, behavioral, and performance
      effects following intranasal administration were similar to the effects following
      intramuscular administration. The relative potency of intranasal heroin was
      estimated to be approximately one-half that of intramuscular administration. The
      efficacy of the intranasal route, combined with decreased heroin cost, reduced
      fear of infection, and the lack of requirements for additional drug
      paraphernalia, could make this an attractive route of drug administration to
      naive or infrequent drug users.

PMID- 8271779
TI  - Cocaine and metabolite excretion in saliva under stimulated and nonstimulated
      conditions.
AB  - The accessibility of saliva for rapid, noninvasive sampling makes it an
      attractive biological fluid for detecting drug use. However, little is known
      about salivary excretion patterns of the major cocaine metabolites,
      benzoylecgonine (BE) and ecgonine methyl ester (EME). Additionally, there is a
      general lack of information on the effects of salivary collection conditions on
      cocaine excretion in saliva. This study documents the profile of cocaine and
      metabolites in human saliva under stimulated and nonstimulated saliva flow
      conditions. Saliva samples were obtained periodically from six healthy volunteers
      who were administered three, equally spaced, single intravenous doses of 25 mg of
      cocaine during a 6-h test session. On different days, whole saliva was obtained
      either under nonstimulated or stimulated (sour candy) conditions. The samples
      were analyzed for cocaine and metabolites by GC/MS. Cocaine, BE, and EME were
      detected and quantitated in the saliva of all subjects. Cocaine was the
      predominant analyte identified in all samples. Nonstimulated saliva contained
      substantially more drug than stimulated samples. The ratio of the area under the
      curve (AUC) of cocaine in nonstimulated saliva to that of stimulated saliva was
      variable and ranged from 3.0 to 9.5. The AUC ratios of BE and EME were similar to
      those observed for cocaine. The lowering of cocaine concentration in saliva in
      the stimulated flow condition was likely due to an increase in saliva pH
      associated with increased saliva flow rate; it is known that an increase in
      saliva pH retards cocaine partitioning into this biological fluid.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8271780
TI  - Benzodiazepine analysis by negative chemical ionization gas chromatography/mass
      spectrometry.
AB  - The application of gas chromatography/mass spectrometry (GC/MS) for the
      simultaneous quantitation of seven commonly encountered urinary benzodiazepine
      metabolites is described. After comparison of the signal-to-noise ratios of high
      mass ions of benzodiazepines using electron impact (EI), positive chemical
      ionization (PCI), and negative chemical ionization (NCI), NCI was chosen because
      of its increased sensitivity, which ranged from four to several thousand times
      that of either PCI or EI. This method is novel because NCI spectra for many of
      these compounds have not been described. For quantitation of benzodiazepines in
      urine, sample preparation consisted of enzymatic hydrolysis, liquid-liquid
      extraction, and reaction with a silylating reagent to form trimethylsilyl
      derivatives. The extraction efficiency of the method was greater than 70% (range,
      73-89%) for nordiazepam, oxazepam, temazepam, lorazepam, N-1
      hydroxyethylflurazepam, alpha-hydroxyal-prazolam, and alpha-hydroxytriazolam; the
      linear range for these compounds was from 50 to 2000 ng/mL. Within-run precision
      was less than 6% for all analytes in the range 50-2000 ng/mL; however, run-to-run
      precision ranged from 3 to 21%, depending on the analyte and concentration.
      Quantitation was based on area ratio of high mass ions relative to deuterated
      internal standards, acquired by scanning the mass range from m/z 250 to 450.
      Because these studies were performed in the scan mode, if desired, the
      sensitivity could be increased by using selected ion monitoring.

PMID- 8271781
TI  - m-Hydroxybenzoylecgonine: an important contributor to the immunoreactivity in
      assays for benzoylecgonine in meconium.
AB  - Meconium has been reported to be a more suitable specimen than maternal or
      neonatal urine for detecting fetal exposure to cocaine. In a study comparing
      various immunoassays with gas chromatography/mass spectrometry (GC/MS), several
      unexplained discrepancies among the assays were noted. Using methanol extracts of
      meconium samples, an immunoreactive spot that was more polar than benzoylecgonine
      was detected by thin-layer chromatography (TLC). An extract of this spot analyzed
      by GC/MS yielded a fragmentation pattern indicative of an aryl hydroxylated
      benzoylecgonine. Standards of m-hydroxybenzoylecgonine, o-hydroxybenzoylecgonine,
      and p-hydroxybenzoylecgonine were synthesized; it was determined that m
      hydroxybenzoylecgonine had the same retention time and ion ratios as the TLC
      immunoreactive spot. Furthermore, m-hydroxybenzoylecgonine proved to be
      immunoreactive. Ten meconium samples immunoreactive for benzoylecgonine were
      analyzed by GC/MS. Results before and after hydrolysis with beta-glucuronidase
      (type IX) showed free m-hydroxybenzoylecgonine comprising 59 to 94% of the total
      m-hydroxybenzoylecgonine and showed total m-hydroxybenzoylecgonine values ranging
      from 0.2 to 6.3 times as high as benzoylecgonine. Therefore, m
      hydroxybenzoylecgonine appears to be a quantitatively important cocaine
      metabolite in meconium, which is responsible for a significant portion of the
      discrepancy between benzoylecgonine concentrations in meconium extracts as
      measured by immunoassay and GC/MS.

PMID- 8271782
TI  - Solid-phase extraction and GC/MS quantitation of cocaine, ecgonine methyl ester,
      benzoylecgonine, and cocaethylene from meconium, whole blood, and plasma.
AB  - A selective solid-phase extraction technique has been applied to the analysis of
      cocaine and selected cocaine metabolites in meconium, whole blood, and plasma.
      This technique uses a mixed-mode Bond Elut Certify column that utilizes the
      characteristics of hydrophobic and polar interactions and ion exchange
      chromatography. Following extraction, cocaine, ecgonine methyl ester,
      benzoylecgonine, and cocaethylene were identified and quantitated using GC/MS.
      Linear quantitative response curves have been generated for the metabolites over
      a concentration range of 0-1000 ng/g for meconium and 0-1000 ng/mL for whole
      blood and plasma. The overall extraction efficiencies, depending on the
      metabolite, were between 58.1 and 99.7% for meconium, 95.6 and 124.0% for blood,
      and 86.9 and 128.9% for plasma. Linear regression analyses of the standard curve
      for the four analytes exhibited correlation coefficients ranging from 0.850 to
      0.946 for meconium, 0.939 to 0.993 for whole blood, and 0.981 to 0.996 for
      plasma. Because of its capability to detect cocaethylene in meconium, blood, and
      plasma, the procedure can be used to determine if drug exposure occurred during
      the latter stages of gestation and if it involved only cocaine or a combination
      of cocaine and ethanol.

PMID- 8271783
TI  - Detection of amphetamine and methamphetamine in urine by gas
      chromatography/Fourier transform infrared (GC/FTIR) spectroscopy.
AB  - New methods for identification of amphetamines have been employed using gas
      chromatography/Fourier transform infrared spectroscopy (GC/FTIR). These methods
      have provided identification of the drug and its metabolites, with detection at
      the low picogram levels or less than 10 ng/mL. Developments in cryogenic sample
      deposition for GC/FTIR spectroscopy have increased the sensitivity of GC/FTIR to
      levels that match or surpass that of gas chromatography/mass spectrometry
      (GC/MS). This advancement in technology has allowed the highly selective ability
      of infrared spectroscopy to be used for identification and quantitation in
      studies where the analytes are in low concentrations. The limits of detection
      (LOD), quantitation (LOQ), and linearity (LOL), and precision have been
      determined in this study, and these instrumental parameters have been compared
      with those of established techniques.

PMID- 8271784
TI  - Evaluation of Emit II reagents on the Chem 1.
AB  - An evaluation study of Syva Emit II reagents using the Chem 1 was performed for
      the following drugs: barbiturates, benzodiazepines, cannabinoids,
      benzoylecgonine, opiates, and phencyclidine. The Emit II reagents (100-mL
      bottles) were reconstituted to 70 mL and evaluated against the Emit d.a.u.
      reagents. A minimum of 446 samples were run for each drug. For all drugs tested,
      there were a total of 11 discordant results between the two reagents. The Emit II
      reagent was found to be correct on 8 of the 11 discordances after retesting by
      FPIA or GC/MS. The CV of within-run and day-to-day precision of the Emit II was
      1.8% or less and 12.3% or less, respectively.

PMID- 8271785
TI  - Determination of thioridazine enantiomers in human serum by sequential achiral
      and chiral high-performance liquid chromatography.
AB  - Quantitation of thioridazine (TRZ) enantiomers, (+)-TRZ and (-)-TRZ, in patient
      serums was performed by a sequential achiral and chiral HPLC method. The lower
      limit of quantitation was 50 ng/mL for each enantiomer, and the method was linear
      up to 1000 ng/mL. The within-run and between-run precision at 125 and 500 ng/mL
      of each enantiomer yielded coefficients of variation (CV) of less than 10% and
      less than 12%, respectively. Absolute recovery of 250 ng/mL racemic TRZ added to
      serum (n = 9) yielded mean recoveries of 77.2% and 77.8% for (+)-TRZ and (-)-TRZ,
      respectively. Absolute recovery of 1000 ng/mL racemic TRZ added to serum (n = 9)
      yielded mean recoveries of 74.0% and 74.7% for (+)-TRZ and (-)-TRZ, respectively.
      Significantly different TRZ enantiomer concentrations were present in patient
      serums. The mean serum concentration was 110 ng/mL for (+)-TRZ (n = 18), and 317
      ng/mL for (-)-TRZ (n = 21). The ratios of (-)-TRZ to (+)-TRZ ranged from 2.2 to
      5.3, with a mean of 3.3. Variations in the concentration of TRZ enantiomers may
      contribute to the lack of correlation between serum TRZ values and therapeutic
      effect.

PMID- 8271786
TI  - Effect of freezing on the concentration of drugs of abuse in urine.
AB  - Benzoylecgonine, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC
      acid), phencyclidine, codeine, morphine, amphetamine, methamphetamine, and
      lysergic acid diethylamide were dissolved in urine, stored frozen in plastic
      tubes at -16 to -18 degrees C, defrosted, transferred to other tubes, and
      analyzed by gas chromatography/mass spectrometry (GC/MS); no significant loss of
      compound was observed, except for THC-acid, which showed an average loss of 11%,
      ranging from 0 to 34% of the total concentration. The loss is attributed to the
      decrease in solubility of the compound and to adherence to the side of the
      container during freezing.

PMID- 8271787
TI  - An intoxication involving BRON and verapamil.
AB  - A case is presented in which the body of a 19-year-old white male was found in
      his family's quarters by his mother. An autopsy failed to determine the cause of
      death, and specimens were sent out for toxicologic analysis. No ethanol or
      volatile substances were detected in the blood, urine, or vitreous fluid.
      Comprehensive drug testing of the urine identified chlorpheniramine,
      dihydrocodeine, methylephedrine, salicylate, and verapamil. The first three drugs
      listed appear together in an over-the-counter cold medication in Japan, under the
      trade name BRON. Blood quantitations (in mg/L) were as follows: chlorpheniramine,
      2.6; dihydrocodeine, 4.7; methylephedrine, 5.6; salicylate, 150; and verapamil,
      6.0. The cause of death was multiple drug intoxication, and the manner of death
      was suicide.

PMID- 8271788
TI  - Death attributed to ethyl chloride.
AB  - A young college student was found unresponsive, head down in his pillow with a
      metal canister containing ethyl chloride in or beside his right hand.
      Resuscitative efforts failed. Qualitative screening detected ethyl chloride in
      the vitreous fluid and antemortem and postmortem blood. Quantitation was carried
      out on available fluids with the following results: hospital blood, 20 mg/dL;
      postmortem blood, 65 mg/dL; and vitreous fluid, 41.7 mg/dL. No other drugs or
      volatiles were found. Death was subsequently attributed to an overdose or adverse
      reaction to this product.

PMID- 8271789
TI  - A golden opportunity.

PMID- 8271791
TI  - Enterprise liability.

PMID- 8271790
TI  - Urodynamics in female incontinence: basic testing.

PMID- 8271792
TI  - Periorbital edema in a middle-aged woman.

PMID- 8271793
TI  - A young leukemic patient with headache.

PMID- 8271794
TI  - Early syphilis in Tennessee--1992.

PMID- 8271795
TI  - Defensible case made indefensible.

PMID- 8271796
TI  - Health care reform: what patients need to know.

PMID- 8271797
TI  - Nixing the habit.

PMID- 8271798
TI  - Cushing's reflex and intracranial aneurysm.

PMID- 8271799
TI  - Descriptive and predictive validity of a high-risk alcoholism relapse model.
AB  - A major problem with alcoholism treatment is the high rate of early recidivism to
      drinking and re-admission for alcoholism treatment. The objective of this study
      was to retest a model or predict early (within 6 months) re-admission to
      alcoholism treatment using a second independent sample. Additionally, we compared
      a high-risk alcoholism relapse (HAR) model (defined by chronicity of heavy
      drinking, daily alcohol consumption and previous treatment history) with three
      previously defined alcoholism typologies for descriptive and predictive validity.
      Male alcoholics (N = 299) admitted for treatment at a Veterans Affairs inpatient
      treatment program were interviewed and then followed for 6 months after
      discharge. The HAR model identified 107 (35.8%) alcoholics at high-risk for
      relapse prior to discharge. Of the HAR group 61% were re-admitted within 6 months
      compared to 28% of the low-risk alcoholism relapse (LAR) group (OR = 4.0, 95% CI
      = 2.4-6.8). The HAR group was older with a lower socioeconomic status, fewer
      legal problems, more physical and mental health problems and decreased evidence
      of social support. The HAR model was more successful than were the typologies for
      predicting early relapse. The HAR model demonstrates descriptive and predictive
      validity and compares favorably to existing typology models.

PMID- 8271800
TI  - Behavioral marital therapy with and without additional couples relapse prevention
      sessions for alcoholics and their wives.
AB  - This study evaluated whether alcoholics who received couples relapse prevention
      (RP) sessions in the year after short-term behavioral marital therapy (BMT) did
      better than those who did not receive additional RP. Couples (n = 59) with an
      alcoholic husband, after participating in weekly BMT couples sessions for 5
      months, were assigned randomly to receive or not receive 15 additional conjoint
      couples relapse prevention (RP) sessions over the next 12 months. Outcome
      measures were collected before and after BMT and at quarterly intervals for the
      year after BMT. Significant improvements in the alcoholics' drinking and the
      couple's marital adjustment occurred from before to after BMT replicating results
      of our own and other's earlier studies of BMT with alcoholics, and outcomes
      remained significantly improved through 12-months follow-up independent of the
      amount of aftercare received. Given these favorable outcomes overall, the present
      study provided a stringent test of the hypothesized utility of RP. As predicted,
      alcoholics who received RP after BMT had more days abstinent and fewer days
      drinking, maintained their improved marriages better and used behaviors targeted
      by BMT more than those who received BMT alone. The prediction that greater
      continued use of behaviors targeted by BMT would be associated with better
      outcomes irrespective of the amount of aftercare received also was supported. The
      final prediction that couples with more severe alcohol and marital problems at
      study entry would show the greatest additional benefit from RP was not supported.
      The relatively clear-cut findings favoring RP may be due to the fact that RP in
      this study was an intensive, multifaceted booster maintenance intervention
      delivered in a couples format over a lengthy period of time. Moreover, the
      present results occurred during the time that couples were still getting RP.
      Limitations to the generalizability and interpretation of the results are
      discussed.

PMID- 8271801
TI  - Assessing the comparative cost-effectiveness of alcoholism treatments: a comment
      on Holder, Longabaugh, Miller and Rubonis.
AB  - Holder, Longabaugh, Miller and Rubonis (JSA, vol. 53, pp. 517-540, 1991) discuss
      the shortcomings of the empirical literature relevant to an assessment of the
      comparative cost-effectiveness of alcoholism treatment modalities. Their analysis
      is rooted in an attempt to conjoin the literatures pertaining to clinical
      efficacy and costs of alcohol dependence treatment. Holder et al.'s methodology
      is flawed in a number of respects and they exceed the bounds of the evidence when
      they endorse particular treatment modalities as comparatively cost-effective.
      Generalizations as to the relative cost-effectiveness of particular modalities
      are forwarded despite the fact that treatments are applied to persons with
      alcohol problems of widely varying severity. Additional points of contention are
      raised regarding the authors' selection of acceptable studies and interpretation
      of findings. Despite these limitations, Holder et al.'s (1991) analysis is a
      seminal heuristic contribution to the discussion of cost-effectiveness in the
      alcoholism field.

PMID- 8271802
TI  - Changes in alcohol expectancies and drinking behavior among treated problem
      drinkers.
AB  - Research on alcohol expectancies among clinical populations has not focused on
      the extent to which changes in alcohol expectancies correspond to changes in
      drinking. In this investigation, male and female problem drinkers participating
      in an outpatient treatment focused on drinking reduction techniques provided data
      on drinking behavior and alcohol expectancies at pretreatment, posttreatment and
      at an 18-month follow-up. Results showed a significant relationship between
      decreases in alcohol expectancies and decreased drinking. Decreases in alcohol
      expectancies were not found over the course of the 8-week treatment, but instead
      at the 18-month follow-up. Implications and future research needs are discussed.

PMID- 8271803
TI  - Peripheral nerve functions improve in chronic alcoholic patients on abstinence.
AB  - We studied the peripheral nerve functions of 24 chronic alcoholic patients
      admitted to the alcohol rehabilitation ward. The study included clinical
      examination, detailed evaluation of nutritional status, quantitative vibration
      sense estimation and electrodiagnostic study of the peripheral nerves in the
      upper and lower limbs. During the subsequent 6 months all of the above measures
      were repeated at invervals of 1, 3 and 6 months, while the patients abstained
      from alcohol. Several of the parameters studied showed mild but definite
      improvement during 6 months.

PMID- 8271804
TI  - Problem-solving deficits in alcoholics: evidence from the California Card Sorting
      Test.
AB  - In an attempt to clarify the nature of the problem-solving deficits exhibited by
      chronic alcoholics, the California Card Sorting Test (CCST) and other measures of
      abstraction and problem solving were administered to 23 alcoholics and 16
      nonalcoholic controls, equated for age, education and vocabulary. On the CCST,
      the alcoholics exhibited three types of deficits which appeared to be relatively
      independent. First, the alcoholics generated and identified fewer correct
      concepts than controls, although they executed concepts normally when cued by the
      examiner. Second, the alcoholics made more perseverative sorting responses and
      perseverative verbal explanations for their sorting behavior than did controls.
      Third, alcoholics provided less complete verbal explanations of the concepts that
      they correctly generated or identified. The differential importance of these
      factors on various measures of problem solving may help to explain the varied
      patterns of inefficient problem solving exhibited by alcoholics.

PMID- 8271805
TI  - What's in a label? The effects of substance types and labels on treatment
      considerations and stigma.
AB  - Visitors (N = 579) to a science center read selected scenarios and evaluated the
      most likely outcome for a hypothetical substance abuser. Respondents were
      randomly assigned to one of six scenario conditions: a person with one of three
      different substance abuse problems (alcohol, tobacco, or cocaine) was crossed
      with two labels reflecting high or low substance dependence. Results indicated
      that: (1) cigarettes were viewed as a less serious substance abuse problem than
      were alcohol or cocaine (a person who smoked cigarettes was rated as more likely
      to recover from his problem, self-change was regarded as more appropriate and
      less stigma was associated with smoking than with the other two drugs); (2) non
      abstinent recoveries of all types were greeted with skepticism; and (3) recovery
      was rated as more likely to occur from treatment than from self-change.

PMID- 8271806
TI  - Development of a scale for measuring impaired control over alcohol consumption: a
      preliminary report.
AB  - Impaired control over drinking has occupied a central place in explanations of
      alcohol dependence since the late 18th century. Despite this key theoretical
      role, no instrument has been developed to directly assess the construct. This
      article describes the development of a three-part Impaired Control Scale (ICS),
      in which Part 1 measures the degree to which a subject has attempted to exercise
      control over drinking in the past 6 months; Part 2 measures the degree of success
      in controlling drinking over the past 6 months; and Part 3 measures the subject's
      belief in his or her ability to control drinking if it were attempted.
      Psychometric analysis showed that, despite difficulties reported in the
      literature, impaired control could be measured in a reliable fashion, with
      satisfactory discriminant and concurrent validity. Preliminary investigation of
      the relationship between the ICS and elements of the alcohol dependence syndrome
      suggests that the construct of impaired control is related to, but may be
      distinguished from, a general factor of alcohol dependence. While more research
      is needed to replicate these findings and to examine interrelationships among the
      various parts of the ICS, the scale may have both theoretical and practical value
      in research and treatment for alcohol dependence and its related problems.

PMID- 8271807
TI  - Development of a behavior analytically derived alcohol-specific role-play
      assessment instrument.
AB  - Social learning theory postulates that chronic alcohol abusers may have deficits
      in ability to cope with stressful situations, and these deficits may be
      associated with relapse after treatment. Attempts to study the hypothesized
      deficits have been hampered by methodological problems. Therefore, a behavior
      analytic procedure was used to develop 10 categories of situations based on over
      600 drinking situations elicited from alcoholics. Role plays were developed for
      each of these categories, and samples of alcoholics in treatment were asked to
      respond as if they were trying not to drink. Videotaped responses were
      behaviorally rated by trained judges for skill and anxiety, and subjects
      completed self-report ratings of urge to drink, anxiety, difficulty and skill
      after each role play. Good interrater reliabilities and internal consistency were
      found across three samples of alcoholics, with virtually no gender differences.
      Previous and current investigations show the validity and utility of this
      instrument. The Alcohol Specific Role Play Test therefore shows promise as a
      means of assessing alcoholics' reactions to high-risk situations.

PMID- 8271808
TI  - The validity of the MMPI in identifying alcoholics in a university setting.
AB  - The predictive validity of MMPI-based alcoholism scales in identifying alcoholism
      and other substance dependencies was evaluated in a naturalistic setting. Study
      participants were 466 male and female college students who completed the MMPI and
      the substance use disorder modules of the Diagnostic Interview Schedule. Results
      indicated that the MacAndrew Alcoholism Scale (MAC), the Substance Abuse
      Proclivity Scale (SAP) and the clinical scales of the MMPI had a poor ability to
      identify the 57 study participants who met DSM-III-R criteria for a substance use
      disorder, primarily alcoholism. Broadening the definition of substance abuse to a
      continuum of alcohol/drug problems did not improve the utility of the MMPI
      scales. Five screening questions that inquired about the consequences of alcohol
      and drug use were moderately effective in substance dependence identification and
      superior to the MAC, SAP and MMPI clinical scales. Results are consistent with
      previous research which concluded that the use of the MAC to identify alcoholics
      in clinical settings is not empirically justified.

PMID- 8271809
TI  - Comparability of self-report of familial alcoholism among male and female college
      students.
AB  - There is a general impression in the literature that women are more accurate
      reporters of familial psychiatric history. In this regard, this study presents
      data from a large cohort of young men (n = 427) and women (n = 607) who in
      answering a questionnaire self-reported alcohol abuse symptoms for various
      biological relatives. No significant gender differences emerged for any of the
      family history comparisons including reports for father, mother, either parent,
      any first- or second-degree relatives, or men or women relatives. The findings
      are discussed in the context of the existing literature.

PMID- 8271810
TI  - A prospective study of the natural course of alcoholism in a Native American
      village.
AB  - This study examines the natural course of alcoholism in a Native American
      village. We found that the remission rates of alcoholism were quite similar
      despite the different methods used: life histories (SADS-L interview) showed a
      63% remission rate; a 19-year follow-up prospective showed 60% in remission; and
      following a cohort of all those who developed alcoholism in the village over the
      previous 19 years revealed a 60.9% remission rate. The data also showed vast
      differences in drinking problems between men and women. In the span of 19 years,
      the differences of point prevalence rates of alcoholism between men and women
      have jumped from that of two times (52% vs 26%) to five times (36.4% vs 7%).
      Furthermore, the results showed women had a higher rate of alcohol abuse (8.4% vs
      3.6%) and a far higher remission rate (82% vs 52%) when compared to men. Three
      fourths of the men in the studied sample had a lifetime history of alcohol
      dependence. They usually began drinking in their teens and developed dependency
      by their early twenties. About half stopped after an average of 15 years of
      drinking. The majority (83%) of the subjects who stopped drinking did so
      spontaneously or for specific personal-related reasons rather than because they
      received alcohol treatment.

PMID- 8271811
TI  - The geographic relationship between alcohol use, bars, liquor shops and traffic
      injuries in Rotterdam.
AB  - Within the scope of the World Health Organization's program "Health for All by
      the Year 2000," a health information system for Rotterdam neighborhoods was
      developed. Through this information system, among others, data on geographic
      distribution of alcohol use, bars, liquor shops and traffic accidents are
      collected. Research has been done on the geographic relationship between the
      percentage of alcohol users and numbers of bars, liquor shops and traffic
      injuries. Significant correlations were found between the percentage of alcohol
      users and traffic injuries per neighborhood, the number of bars and traffic
      injuries per neighborhood and the percentage of alcohol users and number of
      liquor shops per neighborhood. Although confounding of the data occurs, the
      observed relations can be logically explained. Knowledge of the geographic
      relation between alcohol use, traffic injuries and number of bars can be useful
      for further development of multi-sectoral health policies.

PMID- 8271812
TI  - Trends in alcohol intake in a southern German population from 1984-1985 to 1989
      1990: results of the MONICA Project Augsburg.
AB  - This study was undertaken to measure trends in alcohol intake from 1984-85 to
      1989-90 in a southern German population. In the surveys of the MONICA Augsburg
      Project conducted in 1984-85 (Survey 1) and 1989-90 (Survey 2) data on alcohol
      intake (in grams/day) were gathered from two independent representative samples
      (Survey 1: 4,016; Survey 2: 3,960) of men and women, aged 25 to 64 years. A
      validated recall method was applied. Self-reported mean alcohol intake was high
      in Survey 1 (36 g/day in men; 11 g/day in women), but decreased from Survey 1 to
      Survey 2 in both men and women (32 g/day in men; 9 g/day in women). The decrease
      is reflected also in the median and 95th percentile values of alcohol intake and
      in an increase of the proportion of self-reported nondrinkers from Survey 1 to
      Survey 2. Alcohol intake in the MONICA Augsburg population is rather high in
      comparison to other countries, but a trend to lower intakes was observed from
      1984-85 to 1989-90.

PMID- 8271813
TI  - Experimental design in alcohol administration research: limitations and
      alternatives in the manipulation of dosage-set.
AB  - This article reviews literature on the utility of different experimental designs
      in human alcohol administration research, with particular attention to the
      balanced-placebo design (BPD). Many believe the BPD can orthogonally manipulate
      alcohol's pharmacological effects and the effects of dosage-set (believing that
      one has consumed a certain amount of alcohol). However, research has accumulated
      that suggests these effects cannot be disentangled at moderate to high doses of
      alcohol. The strengths and weaknesses of a number of experimental designs are
      discussed with regard to the variables that designs can assess or control.
      Methodological issues in deception conditions and manipulation checks are
      reviewed. Topics in need of empirical investigation are highlighted. It is
      concluded that the appropriate alcohol administration design depends on the
      particular theoretical and methodological issues of a research program.

PMID- 8271814
TI  - Repair of cranial defects with teflon: a method of cranioplasty in monkeys.
AB  - Magnetic resonance imaging demonstrated the need for cranioplasty in experimental
      neurobehavioral studies with non-human primates. Postoperatively temporal lobes
      showed substantial deformation of the neocortex due to pressure from the
      overlying muscle. A new method of cranioplasty using teflon to cover a cranial
      defect has been developed. Teflon is easily shaped and fitted into place. This
      method is safe, allows for the natural shape of the brain, provides protection,
      and is compatible with imaging techniques. Cranioplasty with teflon should be
      considered whenever craniotomy is necessary for accessing the brain.

PMID- 8271815
TI  - Randomization tests: application to single-cell and other single-unit
      neuroscience experiments.
AB  - The application of randomization tests for statistical determination of the
      significance of experimental manipulations on single cells and other types of
      single units in neuroscience is described. Applications of standard parametric
      tests like analysis of variance (ANOVA) and t tests to data from single-subject
      experiments have been severely criticized for lack of validity and those
      criticisms are relevant to parametric statistical tests for data from other types
      of single-unit experiments. A broad class of statistical tests known as
      randomization tests, on the other hand, has been free of such criticism.
      Randomization tests have been applied to data from various types of single units
      in neuroscience, where their validity in the absence of random sampling makes
      them especially valuable. Until the advent of computers, the computational
      requirements of randomization tests rendered them impractical. Randomization test
      computer programs are now readily available. Procedures for access to a public
      domain program are given in the text.

PMID- 8271816
TI  - An in vivo technique for 3-dimensional field mapping in the rodent spinal cord.
AB  - The purpose of this investigation was to develop a reliable method for in vivo
      mapping of small exogenously applied electrical fields in the mammalian spinal
      cord. Experiments were performed in vitro to validate the technique in addition
      to recordings made in vivo on normal and spinal cord injured rats. Sine waves of
      1.5-50 microA and 0.5-50 Hz were used for stimulation. Field gradients were
      measured with a lock-in differential amplifier. Glass recording micro-electrodes
      were used for in vivo experiments. The accuracy of the technique was found to be
      highly dependent on the waveform of the current and impedance matching between
      the recording electrodes. Recordings made in vivo demonstrated that measured
      fields were linearly related to the intensity of stimulation. Field gradients
      were not influenced by stimulation frequencies of 5-50 Hz. Estimates were made of
      the influence of the surgical exposure on the measured gradients. Our results
      demonstrate that small electrical fields can be accurately mapped in vivo and
      interpolated throughout a broad range of intensities and frequencies.

PMID- 8271817
TI  - Cryopreservation of freshly isolated synaptosomes prepared from the cerebral
      cortex of rats.
AB  - In the present study, we established a cryopreservation method for freshly
      isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared
      synaptosomes were either shock-frozen or frozen under temperature-controlled
      conditions using a programmable temperature controller. Each group was
      resuspended in iso-osmotic or hyperosmotic sucrose buffer prior to freezing,
      resulting in 4 different preservation protocols. The viability of the frozen
      synaptosomes was estimated by the recovery of basal and stimulated respiration
      after short-term storage (1 h) in liquid nitrogen. With regard to basal, FCCP-
      and veratridine-induced respiration, best recovery revealed controlled-frozen
      synaptosomes resuspended in iso-osmotic sucrose buffer (con/iso group). Basal
      respiration of this group recovered completely, whereas veratridine- and FCCP
      induced oxygen uptake was decreased to 87.7% and 82.4% of control, respectively.
      Further investigations performed with the con/iso group revealed complete
      recovery of anaerobic and aerobic lactate synthesis, and unaffected synaptosomal
      integrity, as judged by the amount of released L-lactate dehydrogenase before and
      after the cryopreservation procedure. Long-term storage of the con/iso group in
      liquid nitrogen up to 88 days did not have any influence on synaptosomal
      viability, as evaluated by the recovery of anaerobic lactate production and
      synaptosomal respiration. Therefore, based on the results of respiration,
      synaptosomal integrity, and lactate synthesis, metabolically active synaptosomes
      could be obtained after cryopreservation and storage in liquid nitrogen for at
      least 88 days.

PMID- 8271818
TI  - A stimulator for studies of mechanical nociception based upon a commercially
      available translation table.
AB  - We have developed a mechanical stimulator that can be used for studies of sensory
      physiology, psychophysics and tissue mechanics. The stimulator operates in either
      displacement or force-servo modes. It surpasses other available stimulators in
      respect to displacement range, measurement sensitivity and cost, and it can be
      easily assembled from parts that are commercially available.

PMID- 8271819
TI  - Simulation of epileptiform activity in the hippocampus using transputers.
AB  - Transputer technology is exploited to provide fast and interactive simulations of
      the electrical behaviour in large networks of neurones derived from experimental
      data of individual neurones and their connections. A synchronous numerical
      integration routine and an efficient communication scheme have been developed to
      run on toroidally configured transputer arrays of any sizes. A population of
      neurones up to 6400 from the hippocampus has been simulated on 19 Inmos T800
      transputers. The activity of individual cells has been modelled using a similar
      approach to that of Traub; but the non-linear dynamics of the Na(+)-K+ channels
      is emphasised to explain intrinsic bursting. This model includes a description of
      the cellular channel currents INa, IK(DR), IK(C), ICa and IAHP. Preliminary
      studies indicate that this anatomically based model can be used to study the
      dynamic properties of neurones in the hippocampus, including monitoring the
      behaviour of subpopulation of cells that contribute to epileptiform activity.

PMID- 8271820
TI  - A simple computer-based method for performing and analyzing intracranial self
      stimulation experiments in rats.
AB  - Intracranial self-stimulation (ICSS) in the rat is a useful tool for studying the
      importance of various brain monoamines in positive reinforcement. The effects of
      compounds interacting with dopaminergic neurotransmission is measurable by
      studying the changes of reward thresholds. By computerisation of the analysis of
      these thresholds, standardisation and reproducibility is greatly enhanced. The
      use of an object-oriented programming language simplifies the programming of a
      specific application and it provides scientists without formal training in
      computer programming the means to create their own software. A system for the
      acquisition, execution, analysis and storage of ICSS experiments is described.
      The hardware is based on Apple Macintosh computers, interfaced to the test
      chambers and physiological stimulators using a plug-in card supporting A/D, D/A,
      digital I/O and timer functions. The software written in G (LabVIEW) provides the
      user with a graphically based 'Virtual Instrument' performing all aspect of the
      ICSS experiment. The software performs threshold analysis immediately after
      completion of the ICSS experiment, thereby greatly reducing the total time
      previously needed to evaluate these experiments. The graphical approach used in
      LabVIEW allows the programmer to make fast and simple alterations to suit
      different experimental problems.

PMID- 8271821
TI  - Diethylene glycol distearate (DGD): a versatile embedding medium for retinal
      cytochemistry.
AB  - Embedment in diethylene glycol distearate (DGD) was shown to be highly desirable
      and versatile for retinal cytochemical studies, including in situ hybridization,
      immuno- and lectin cytochemistry. This method allows for preservation of fine
      tissue detail as well as good reaction sensitivity. It appears to be more
      suitable than most other methods currently used for light microscopic retinal
      cytochemistry.

PMID- 8271822
TI  - A device for transplantation of single cells.
AB  - A device with a high degree of precision is described for the transplantation of
      single identified cells in specified regions of the host brain. It consists of
      two co-centric micropipettes where the inner pipette, functioning as a plunger,
      is used to drive the cells contained near the tip of the outer pipette into the
      host. The use of a pre-calibrated micrometer to control the movement of the inner
      pipette obviates the need of visual monitoring for successful transplantation.

PMID- 8271823
TI  - Evaluation of a microsensor intracranial pressure transducer.
AB  - This report describes the results of a laboratory evaluation of a new device for
      monitoring intracranial pressure (ICP), consisting of a miniature pressure
      transducer mounted on a pressure sensing diaphragm. In in vitro tests, 6
      microsensor transducers were monitored for drift at pressures of 10 mmHg and 20
      mmHg. The maximal drift of any of the transducers was 1 mmHg over 9 days. In in
      vivo tests, the ICP measurement obtained with the microsensor transducer
      correlated well with pressures recorded from a catheter in the cisternal magna
      with a Statham transducer over a wide range of ICP values (n = 511, r = 0.998, P
      < 0.001). If these laboratory findings can be duplicated in clinical studies,
      this microsensor transducer may be a useful alternative to the ventriculostomy
      catheter and other currently used devices for monitoring ICP.

PMID- 8271824
TI  - A compartmentalized chamber for studying dopamine neurons in an hypothalamo
      pituitary explant.
AB  - An in vitro technique was developed which could be used to study whole neurons of
      the tuberohypophyseal dopaminergic (THDA) tract. Explants containing the medial
      basal hypothalamus (MBH; THDA cell bodies), pituitary stalk (THDA axons) and
      posterior pituitary (PP; THDA nerve terminals) were carefully dissected and
      placed in specially designed chambers. The chambers consist of separate
      compartments for the incubation of the MBH and PP while maintaining an intact
      pituitary stalk which traverses through a notched barrier. Dopamine (DA)
      synthesis in the explants was constant for 3 h and was significantly elevated by
      electrical stimulation. Electrical stimulation of both the PP and MBH increased
      endogenous DA release from the PP. DA release in response to potassium
      depolarization and dopaminergic drugs was significantly lower in explants than in
      the isolated PP even though spontaneous release was similar. CONCLUSIONS: (1)
      this method is suitable for studying intact THDA neurons in vitro, and (2) intact
      THDA neurons respond differently to various stimuli than their excised terminals.

PMID- 8271825
TI  - A method for producing unbiased histograms of neuronal profile sizes.
AB  - An important goal in neuroscience is to produce frequency distribution curves or
      histograms that relate numbers of cells to their sizes. Unfortunately such
      histograms, which are extremely common, are biased. Some of the reasons are
      inadequate attention to sampling paradigms, the lack of assurance that the
      section through the center of the cell is measured, and that large cells will
      have more profiles than small cells. The first goal of this paper is to
      illustrate these biases for dorsal root ganglion cells by showing significant
      statistical differences between histograms prepared the classic way and
      histograms produced by unbiased methods. The differences are particularly
      dramatic for plastic embedded material. The second goal of the paper is to
      describe an unbiased method for obtaining these histograms. The procedure is 2
      fold. Cells are chosen in an unbiased way (unbiased in this sense means that
      every cell has an equal chance of being chosen), and then the largest profile of
      the cell is measured. We further suggest that these histograms be accompanied by
      analyses of cell volume, since volumes of cells rather than diameters or areas of
      cell profiles, will be the future measure of choice when considering the sizes of
      cells (or any other particles of biologic interest).

PMID- 8271826
TI  - An unbiased correction factor for cell counts in histological sections.
AB  - It is common procedure to correct raw counts of cells (or nuclei or other such
      particles) in histological sections by multiplying them by a 'correction factor',
      to allow for sectioned particles being counted more than once. However, the
      derivation of the standard formulae assumes that the particles to be counted are
      of uniform size. Therefore, these formulae may be biased in practical situations.
      Here, a more general correction factor (C) not depending on this restrictive
      assumption is derived: C = sigma i = 1 m T/(T - h(i))/sigma i = 1 m (T - R - S +
      h(i))/(T - h(i)) where T is section thickness, h(i) is the height of particle i
      measured perpendicular to the section plane, R and S are the heights, assumed
      constant, of the upper and lower 'lost caps', and the summation is performed over
      m (about 20) particles sampled randomly from among those lying wholly within
      individual sections. It is proposed that h(i) be measured by a differential
      focusing method; the formula will then be valid for particles of variable shape
      as well as size.

PMID- 8271827
TI  - A rapid and efficient method for the radiosynthesis and purification of
      [125I]SCH23982.
AB  - The radiosynthesis of (1R)-(+)-1-phenyl-3-methyl-7-[125I]iodo-8-hydroxy- 2,3,4,5
      tetrahydro-1H-3-benzazepine (commonly referred to as SCH23982) and its use as a
      high affinity D1 dopamine antagonist ligand have been reported previously. We now
      provide a simple and inexpensive protocol for the rapid and efficient synthesis
      of this radioligand based on the Cloramine-T-catalyzed reaction between the
      commercially available precursor (R)-(+)-1-phenyl-3-methyl- 8-hydroxy-2,3,4,5
      tetrahydro-1H-3-benzazepine and carrier-free sodium [125I]iodide. [125I]SCH23982
      is separated rapidly (within 20 min) from the precursor and reaction byproducts
      (e.g., chlorinated precursor, SCH23390) by reverse-phase HPLC on a C-8 column.
      The major iodinated product has been identified as SCH23982 based on co
      chromatography with authentic SCH23982, UV spectral characteristics, and
      biological activity. The chromatographic effluent containing the active product
      is adsorbed on a C-18 Sep-Pak cartridge to remove mobile-phase constituents and
      permit it to be eluted and diluted to the desired concentration; this technique
      is used also for periodic repurification. Our synthesis protocol results in final
      purified product that incorporates ca. 50% of the initial 125I (tested using
      starting quantities of 1-10 mCi Na125I); the final product has a specific
      activity of ca. 2500 +/- 350 Ci/mmol. Data from in vitro receptor
      autoradiographic and homogenate studies with this radioligand are consistent with
      previously reported values in terms of expected receptor distribution, affinity,
      and density (KD of 1.0 nM, Bmax of 1400 fmol/mg protein in rat striatal
      membranes).

PMID- 8271828
TI  - Method for distinguishing between drug action on impulse propagation versus
      impulse generation.
AB  - Systemic or regional application of local anaesthetics or tetrodotoxin eliminate
      repetitive impulse discharge, but do they do so by blocking impulse propagation
      or by suppressing impulse initiation? A method is described for making this
      distinction based on differences in the pattern of discharge change during the
      onset of the block. Suppression of conductances involved in downstream impulse
      propagation produces integer multiplication of the fundamental interspike
      interval (interspike interval (ISI) doubling, tripling, etc.) In contrast,
      progressive block of conductances responsible for either the creation of the
      generator potential, or for its encoding into a spike train, causes a smooth
      increase in the rhythmic ISI. These two patterns of block, predicted on the basis
      of fundamental principles and numerical simulations, were verified in in vivo
      single-axon recordings.

PMID- 8271829
TI  - Culture of hypoglossal cells, dissociated from foetal and new-born rats.
AB  - Primary cultures of dissociated cells from brainstem cranial nuclei have not been
      described in the literature. The present paper shows that dissociated rat
      posterior brainstem cells, as well as cells from the hypoglossal nucleus, taken
      from both foetal and postnatal animals, can be maintained in long-term culture.
      This can be achieved by using a DMEM/F-12 medium with defined supplements, with
      or without foetal calf serum. Under such conditions, the growth of neuritic
      processes as well as the formation of neural networks can be observed. The
      different cell types present in the cultures can be identified by
      immunohistochemistry with antibodies raised against neuron specific enolase,
      glial fibrillary acidic protein, galactocerebroside and choline-acetyl
      transferase. As previously demonstrated for other brain-dissociated neurones
      maintained in cultures, the use of molecules, involved in cell adhesive
      mechanisms, can modify the morphological properties of the growing cells. This
      was particularly observed when poly-L-lysine and laminin were used as substrata.

PMID- 8271830
TI  - MARDER--multi-axes rotation device for experimental research. A new concept for
      investigations of the vestibular, oculomotor, and visual systems of humans in
      three-dimensional space.
AB  - A hydraulically driven, digitally servo-controlled multi-axes rotary chair is
      described. This device generates motion profiles with the subjects head in the
      center of rotation mainly in order to adequately stimulate the semicircular
      canals which are sensitive sensors for angular accelerations. This newly
      developed apparatus allows for motion stimuli which are below the vestibular
      threshold up to accelerations of 12 rad/s2 (688 degrees/s2) and is thus suitable
      for a variety of experiments in the field of vestibular, oculomotor, and
      intersensory research in 3-dimensional space.

PMID- 8271831
TI  - A discrete adjuvant-induced monoarthritis in the rat: effects of adjuvant dose.
AB  - Much evidence suggests an important role for the nervous system in the
      pathogenesis of peripheral inflammatory conditions such as arthritis. The
      classical adjuvant-induced arthritis model in the rat is a severe condition in
      which polyarthritis is accompanied by widespread systemic disease, complicating
      the interpretation of data. We have developed an adjuvant-induced arthritis of
      the tibio-tarsal joint in the rat, using a low dose of Freund's adjuvant
      administered locally. Initial inflammation is followed, after 14 days, by chronic
      monoarthritis which is maintained without generalised effects or loss of use of
      the limb until at least 30 days postinjection. A higher dose of adjuvant produces
      contralateral inflammation and arthritis, but only after 14 days, and without the
      complicating effects seen in classical adjuvant disease. Indirect measures of
      arthritis (joint circumference, inflammation score and nociceptive threshold)
      correlate closely with the histological state of the joint, supporting the use of
      these indices. This model can be easily exploited by alteration of adjuvant dose,
      to determine the roles of the nervous system in the pathogenesis, maintenance and
      symmetrical spread of inflammatory arthritis.

PMID- 8271832
TI  - A system to measure thermal nociception.
AB  - Hyperalgesia is commonly demonstrated by measuring the difference in latency to
      thermal nociception between a control and injured condition. Historically these
      tests have been conducted using either a hot plate or radiant heat source to
      stimulate thermal receptors in the foot. The design of a simple and inexpensive
      circuit to measure thermal nociception based on a method originally introduced by
      Hargreaves et al. (1988) is described. The design uses a movable, high-intensity
      light source to heat either the right or left footpad of the test animal. The
      advantage of this method is that it permits each animal to serve as its own
      control since the experimental and control footpads can be tested independently.
      The design possesses greater sensitivity than mechanical hyperalgesia test
      procedures and provides an automated endpoint that electronically records the
      latency to removal of the foot from the heat source. Additional features of this
      design which reduce variability include a constant temperature floor to reduce
      the effect of altered footpad temperature that may be caused by autonomic
      dysfunction in the experimental limb and a method of reproducibly locating the
      heat source prior to testing. The response to a unilateral lesion is demonstrated
      with this device.

PMID- 8271833
TI  - Edge detection at multiple locations using a 'radar' tracking algorithm as
      exemplified in isolated guinea-pig lymphatic vessels.
AB  - An algorithm based on the Kalman filter and used for tracking a target in a noisy
      environment has been applied to monitoring the position of moving boundaries as
      recorded by a video camera. The method, termed the Probabilistic Data Association
      Filter, is computationally efficient, allowing simultaneous monitoring at many
      positions along the boundary at video frame rates of 25 Hz. The present study
      uses the tracking procedure to investigate and correlate constrictions along
      lymphatic vessels. The procedure is well suited for real time tracking of
      visualised biological events including the simultaneous monitoring of
      constrictions in networks of blood vessels, the movement of cells or the
      trajectory of intracellular events monitored by intracellular fluorescent
      markers.

PMID- 8271834
TI  - A simple method for recording single-channel activity from synaptic plasma
      membranes.
AB  - Due to the small size of most nerve terminals, the ion channels which underlie
      presynaptic currents are usually inaccessible to investigation by conventional
      electrophysiological techniques. Here we describe a simple method for obtaining
      single-channel recordings from synaptic plasma membranes that does not require
      exposure of the native membranes to exogenous lipids or fusogens. To illustrate
      the method, we have recorded single-channel activity from rat cerebrocortical
      synaptosomal membranes. Under conditions designed to isolate calcium-independent
      currents, we describe three channel types that are most commonly observed.

PMID- 8271835
TI  - A method for finding stereotaxic coordinates from brain sections.
AB  - A method for finding the stereotaxic coordinates of brain areas from actual brain
      sections is presented. It uses a digitizer connected to a computer to gather
      coordinates from photographs of brain sections. The coordinates are
      mathematically translated and rotated to yield stereotaxic atlas coordinates of
      the areas digitized.

PMID- 8271836
TI  - In vitro and in vivo microdialysis calibration for the measurement of
      carbamazepine and its metabolites in rat brain tissue using the internal
      reference technique.
AB  - Microdialysis, as in vivo sampling technique, can be used for determining
      exogenous compounds in the extracellular fluid of freely moving animals and in
      humans. Usually, calibration of the microdialysis probe is determined by in vitro
      relative recovery (RR) (dialysate extraction fraction). However, due to different
      diffusion properties of the compound in tissue, the RR in vivo is different from
      the RR in vitro. In this study, the evaluation of the internal reference
      technique as in vivo calibration method was established. To determine the RR in
      vivo, the relative loss (RL) was defined as the loss of a compound from the
      perfusate. RL was determined in vitro and in vivo by adding an internal standard
      (IS) to the perfusate. This internal reference technique was applied for the
      determination of carbamazepine (CBZ) and its 2 major metabolites, carbamazepine
      10,11-epoxide (CBZ-EPO) and trans-10,11-dihydroxy-10,11-dihydro-carbamazepine
      (CBZ-DIOL) using 2-methyl-5H-dibenz(b,f)azepine-5-carboxamide (m-CBZ) as IS. In
      vitro and in vivo, the loss of m-CBZ and the recovery of CBZ are identical. The
      ratios of the RR of CBZ-EPO and CBZ-DIOL to the RL of m-CBZ are constant, in
      vitro and in vivo. Therefore, m-CBZ can be used as IS for CBZ, CBZ-EPO and CBZ
      DIOL determinations in brain tissue. It is shown that the internal reference
      technique is a useful method to estimate the true concentration of exogenous
      compounds in the extracellular space of tissues.

PMID- 8271837
TI  - A new method for the insertion of multiple microprobes into neural and muscular
      tissue, including fiber electrodes, fine wires, needles and microsensors.
AB  - We developed a new method for the insertion of thin-shaft probes into neural and
      muscular tissue. Axial forces for driving the probes into tissue and radial
      forces against buckling are both provided by a stretched elastic rubber tube in
      which the probe is guided outside the tissue. Various geometric arrangements of
      arrays with independently advanceable probes are possible. Prototypes with 7
      linearly aligned fiber electrodes and computer-controlled positioning motors were
      successfully used in single- and multiple-unit recordings from the visual system
      of awake monkeys (Eckhorn et al., 1993). The method is suitable in a wide range
      of applications, including insertion of fine microprobe fibers and wire
      electrodes into brain and muscle through the skin or dura, provided that the tips
      of the probes are sharp and hard enough.

PMID- 8271838
TI  - Whole intact tissue electrophoresis of nerve proteins.
AB  - We describe a rapid and simple method for analyzing proteins along the length of
      a nerve tissue using sodium dodecylsulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). A long length of nerve tissue is placed on a slab gel, layered with
      SDS-buffer, and electrophoresed. In this whole-intact-tissue procedure, the in
      situ differences in location and/or concentration of protein along the length of
      a nerve tissue are not disturbed by homogenization and dilution prior to
      electrophoresis.

PMID- 8271839
TI  - Polypropylene pellets as an inexpensive reusable substitute for milk in the
      Morris milk maze.
AB  - A new inexpensive opaquing agent for the Morris milk maze is described. Small
      light-weight polypropylene pellets that float on the surface of the water were
      used to eliminate visual cues about the location of the hidden platform without
      impeding swimming or the use of distal spatial cues. Results obtained using the
      pellets are identical to those obtained with milk powder as an opaquing agent. An
      automatic tracking system works as well with the pellet as with the milk version
      of the maze.

PMID- 8271840
TI  - A tungsten-in-glass iontophoresis assembly for studying input-output
      relationships in central neurons.
AB  - A method is described for the production of an electrode capable of monitoring
      and modulating the input-output relationship of thalamic neurons. Tungsten-in
      glass electrodes were manufactured with the ability to simultaneously record
      lateral geniculate nucleus action potentials and associated, retinally evoked S
      potentials. The recording electrodes were mounted onto multibarreled
      micropipettes with iontophoretic capability. The completed electrode assembly
      permitted micropharmacological modulation of the fraction of lateral geniculate
      nucleus output spikes to retinal input spikes (the transfer ratio).
      Iontophoretically applied gamma-aminobutyric acid (GABA) decreased the transfer
      ratio, an effect countered by the GABAA antagonist, bicuculline. Elevated
      transfer ratios produced by stimulation of an afferent pathway originating in the
      parabrachial region of the brainstem were decreased by concurrently applied GABA.
      The fabrication of this electrode assembly employs simple modifications of
      existing techniques and separate construction of recording and iontophoretic
      elements to provide high-quality single-unit recordings coupled with
      micropharmacological function.

PMID- 8271841
TI  - Long-term sleep deprivation by hypothalamic stimulation in cats.
AB  - Several techniques were developed to prevent sleep in animals in order to examine
      the biological role fulfilled by sleep; however, most were either stressful or
      difficult to accomplish routinely, especially in such a large animal as the cat.
      Electrical stimulation of activating structures in the brain presents a very
      attractive alternative to peripheral stimulation used by the usual sleep
      deprivation methods although it has been rarely tried. The paper describes a
      microcomputer-based system used to achieve sleep deprivation in cats by
      stimulating the hypothalamic predatory area with short trains. During control
      days and deprivation the electrocorticogram (EEG), electromyogram (EMG) and
      electrooculogram (EOG) were continuously digitalized by the computer in 5 s
      epochs and the integrated power of the 4 usual frequency bands of the EEG (alpha,
      beta, delta, theta) as well as the variance of EMG and EOG signals were
      calculated. Criteria for stimulus delivery were based on the integrated power of
      the delta band and on the variance of EMG but the flexibility of the computer
      ensures that any other parameter can be used to achieve total or selective sleep
      deprivation.

PMID- 8271842
TI  - Mapping of [3H]vasopressin binding sites in the brain of jerboa (Jaculus
      orientalis) by an high resolution beta-radio imager.
AB  - The distribution of vasopressin receptors in the brain of the jerboa (Jaculus
      orientalis) was studied using tritiated arginin vasopressin ([3H]vasopressin).
      beta-Particles emitted from tritiated ligand bound to brain sections were
      detected by a newly developed beta-radio imager to generate a light spot which
      was read by a charge coupled device camera. The number and coordinate of the
      center of gravity of the light spot were recorded. After summation in pixels of
      the counts collected during 2-20 h, an image was produced representing the
      distribution of [3H]vasopressin bound to brain sections. Specific vasopressin
      binding was detected in various brain regions such as the cerebral cortex,
      islands of Calleja, pallidum, amygdala and the hippocampus as well as in the
      pituitary gland. The intensity of the binding was quantified directly from the
      images obtained and expressed in decays/min/surface unit. The linearity of this
      method of detection allowed a relevant measurement of non-specific binding,
      therefore its subtraction from images representing the total binding. Three
      dimensional reconstructions of labeled structures were also performed. The
      presence of numerous vasopressin receptors in the jerboa hippocampus suggests a
      major role for this neuropeptide in this part of the brain.

PMID- 8271843
TI  - A method for bevelling of microelectrodes by means of vibration.
AB  - A technique for the rapid bevelling of glass and metallic microelectrodes is
      described. The method utilizes end friction of the electrode tips on the fine
      grained surface of a quartz plate vibrating at the mechanical resonance frequency
      of the system. A electromagnetic vibrator is supplied with alternating current at
      a frequency equal to the mechanical resonance frequency of the system (200-300 s
      1).

PMID- 8271844
TI  - Liver iron stores in patients with non-insulin-dependent diabetes mellitus.
AB  - BACKGROUND: Iron overload such as that in idiopathic hemochromatosis is a well
      established, albeit rare, cause of non-insulin-dependent diabetes mellitus
      (NIDDM). Most patients with NIDDM have no recognized cause of their disease.
      Investigators have proposed that subclinical iron overload may cause diabetes
      mellitus in a substantial number of patients with NIDDM. OBJECTIVE: The aim of
      the current study was to evaluate hepatic iron stores in autopsy specimens from a
      group of community residents with NIDDM. METHODS: Fifteen patients with NIDDM and
      17 age-matched control subjects were identified from a review of medical records
      of decreased residents of Olmsted County, Minnesota. Formalin-fixed liver tissue
      was analyzed for iron concentration by flameless atomic absorption
      spectrophotometry, and distribution of hepatic iron was determined
      histochemically. RESULTS: No significant difference was found in either the
      distribution or the mean amount of hepatic iron between the diabetic and the
      control group (1,303 versus 1,349 micrograms Fe/g dry weight; P = 0.87). Thus,
      the mean difference was -46 micrograms Fe/g dry weight (confidence interval, -631
      to 540). CONCLUSION: Because hepatic iron quantification is the definitive means
      of assessing total body iron stores, our results suggest that NIDDM is typically
      not associated with a substantial level of iron overload.

PMID- 8271845
TI  - Circulating heart autoantibodies in familial as compared with nonfamilial
      idiopathic dilated cardiomyopathy.
AB  - BACKGROUND: Idiopathic dilated cardiomyopathy (DCM) is a serious heart disease
      characterized by enlargement of one or both ventricles and ventricular
      dysfunction. Although most patients have sporadic disease, 20% have been found to
      have familial DCM when relatives are investigated by echocardiography. No other
      factors have been identified to date that consistently distinguish familial from
      nonfamilial DCM. Although some patients have a family history of DCM, a
      "negative" family history does not exclude familial DCM because affected family
      members may be presymptomatic or undiagnosed. Because some patients have life
      threatening complications at the time of initial assessment of DCM, identifying a
      serum marker predictive of familial disease would help determine which families
      would most likely benefit from echocardiographic investigation. OBJECTIVE: In
      this study, our objective was to determine whether antiheart autoantibodies could
      be used to distinguish familial from nonfamilial idiopathic DCM. METHODS: We
      analyzed serum specimens for antiheart antibodies from 19 patients categorized as
      having familial DCM and 15 classified as having nonfamilial DCM on the basis of
      echocardiographic investigation of first-degree relatives. The mean duration of
      disease in these 34 patients was 50 months at the time the serum specimens were
      obtained. RESULTS: Titers of antibodies against the adenine nucleotide
      translocator, branched-chain keto acid dehydrogenase, and cardiac myosin did not
      distinguish between familial and nonfamilial cases of DCM.

PMID- 8271846
TI  - Preoperative diagnosis of coronary artery anatomy in dextrotransposition of the
      great arteries.
AB  - BACKGROUND: Preoperative diagnosis of the coronary artery pattern in
      dextrotransposition of the great arteries is important because deviation from the
      usual pattern may influence the surgical strategy. METHODS: For assessment of the
      value of angiography and echocardiography in this setting, we analyzed the
      preoperative echocardiographic and angiographic findings in 74 patients with
      dextrotransposition of the great arteries in whom an arterial switch operation
      was performed. RESULTS: Two-dimensional echocardiography established a diagnosis
      of the coronary artery pattern in 40 of the 74 patients; that diagnosis was
      correct in 38-30 of 32 (94%) with the usual coronary artery pattern and 8 (100%)
      with an atypical pattern. Angiography established a diagnosis of the coronary
      artery pattern in 52 patients; that diagnosis was correct in 50-41 of 42 (98%)
      with the usual coronary artery pattern and 9 of 10 (90%) with an atypical
      pattern. The accuracy of echocardiography in diagnosing the coronary artery
      pattern in dextrotransposition of the great arteries in this series was 95% and
      that of angiography was 96%. CONCLUSION: Both echocardiography and angiography
      can establish the diagnosis of the coronary artery anatomy in most patients.
      Echocardiography is routinely performed in infants with dextrotransposition of
      the great arteries and is proving to be increasingly sensitive for diagnosing the
      coronary artery anatomy; the role of angiography may evolve to be supplementary,
      especially in cases in which the coronary artery anatomy is not clearly
      demonstrated by echocardiography.

PMID- 8271847
TI  - Strictureplasty for obstructive Crohn's disease: the Mayo experience.
AB  - BACKGROUND: Strictureplasty for obstructive Crohn's disease of the small bowel
      continues to gain favor throughout the world. Although the potential advantages
      of preserving intestinal length are obvious, the optimal clinical setting for
      performing strictureplasty remains to be determined. PATIENTS: Of 244 patients
      who underwent abdominal exploration for complications of Crohn's disease between
      Jan. 1, 1985, and Jan. 1, 1991, at the Mayo Clinic, 35 had a total of 71
      strictureplasties. Concomitant resection of bowel with active disease was
      performed in 67% of the procedures. RESULTS: In this series, no perioperative
      deaths occurred, and no anastomotic leaks, enteric fistulas, or intra-abdominal
      abscesses were noted during a 3-year follow-up. The overall perioperative
      complication rate was 14%. Postoperatively, 33 of the 35 patients were able to
      resume enteral nutrition and discontinue medical treatments. The symptomatic
      recurrence rate at 3 years was 20%; six patients have required reoperation.
      CONCLUSION: These findings support the use of strictureplasty for isolated,
      quiescent, stenotic bowel lesions associated with Crohn's disease.

PMID- 8271848
TI  - Isolated bone marrow non-Hodgkin's lymphoma: a clinicopathologic study.
AB  - BACKGROUND: Isolated bone marrow non-Hodgkin's lymphoma (NHL) is rare, and
      determining the diagnosis is difficult. PATIENTS: We describe four patients with
      apparent isolated bone marrow NHL. The features they had in common included
      fever, abnormal liver function, pancytopenia, polyserositis, neurologic symptoms,
      opportunistic infections, and a short, fatal course. FINDINGS: Routine cytologic
      and histologic studies showed intermediate and large lymphomatous cells in the
      bone marrow, with a predominantly interstitial pattern. Immunophenotyping
      revealed three cases of T-cell and one case of B-cell NHL. Cytogenetic analysis
      demonstrated an abnormal clone in two patients. CONCLUSION: The diagnosis of
      isolated bone marrow NHL should be based on the examination of both bone marrow
      aspirates and biopsy specimens.

PMID- 8271849
TI  - Dr. Louis B. Wilson, pioneer Mayo scientist and educator.

PMID- 8271850
TI  - Fine-needle aspiration biopsy of thyroid nodules: advantages, limitations, and
      effect.
AB  - BACKGROUND: The efficacy of fine-needle aspiration (FNA) biopsy and its role in
      the management of a nodular goiter are clearly established. The accuracy of
      cytologic diagnosis approaches 95%. FINDINGS: FNA biopsy is a reasonable approach
      to thyroid nodules; it has decreased costs substantially because it facilitates
      selection of patients who need to undergo surgical excision. Selecting patients
      for operation on the basis of results of FNA biopsy has more than doubled the
      yield of carcinoma. The limitations of cytologic examination, nondiagnostic
      results, and cellular follicular neoplasms should be remembered but need not
      negate continued use of FNA biopsy. Negative (benign) and positive (malignant)
      cytologic results are conclusive; careful clinical follow-up of benign nodules
      and surgical excision of malignant nodules are recommended. Nondiagnostic results
      are inconclusive; further evaluation by repeated FNA biopsy, ultrasound-guided
      biopsy, or radionuclide scanning is necessary. Suspicious cytologic results are
      also inconclusive and are associated with a 20% chance of malignant involvement;
      surgical treatment is necessary for clarification. The role of levothyroxine
      therapy remains uncertain and is not recommended until compelling data are
      available. CONCLUSION: FNA biopsy is a safe, simple, reliable, and cost-effective
      means of detecting benign nodules. FNA biopsy, not thyroid scanning or
      ultrasonography, is the preferred initial diagnostic test in all patients with
      thyroid nodules.

PMID- 8271851
TI  - Cost comparison of immediate angioplasty versus thrombolysis followed by
      conservative therapy for acute myocardial infarction: a randomized prospective
      trial. Mayo Coronary Care Unit and Catheterization Laboratory Groups.
AB  - OBJECTIVE: Immediate angioplasty and thrombolysis followed by conservative
      therapy are treatment strategies for acute myocardial infarction. The objective
      of this study was to compare the costs of these two strategies during a 12-month
      period. METHODS: Of 103 patients with acute myocardial infarction who sought
      medical assistance within 12 hours after onset of symptoms, 4 were excluded from
      analysis for various reasons, 51 received tissue plasminogen activator, and 48
      underwent immediate angioplasty as the initial revascularization strategy. The
      main outcome determinants were direct monetary costs and indirect measures of
      costs, including duration of hospital stay and return to work. RESULTS: No
      significant difference in monetary costs between the two initial treatment
      strategies could be demonstrated. A trend was noted toward a briefer hospital
      stay and fewer late in-hospital procedures for patients treated initially with
      immediate angioplasty. Other measures of indirect costs were not statistically
      different. CONCLUSION: The hypothesis that thrombolysis followed by conservative
      therapy would be more cost-effective than immediate angioplasty in the treatment
      of patients with acute myocardial infarction could not be substantiated. The two
      strategies seem to have similar cost-effectiveness.

PMID- 8271853
TI  - Immunohistochemical stains for breast cancer.

PMID- 8271852
TI  - Current management of retinoblastoma.
AB  - OBJECTIVE: The recommended management of retinoblastoma based on personal
      experience with the assessment and treatment of more than 450 children with this
      intraocular malignant lesion is presented. RECOMMENDATIONS: Although
      retinoblastoma is usually managed by enucleation, the treatment of each case must
      be individualized; in an increasing number of children, the techniques of
      irradiation, photocoagulation, or cryotherapy are being used. In some patients, a
      combination of these techniques is necessary. Chemotherapy is often used to
      prevent distant metastatic involvement, although its effectiveness as a
      prophylactic treatment has not been clearly established. Because metastatic
      retinoblastoma is often fatal, intense chemotherapy is recommended in this
      setting. CONCLUSION: The prognosis for vision and life in patients with
      retinoblastoma has improved considerably during the past century, primarily
      because of earlier recognition of the tumor and use of modern therapeutic
      methods. All children of parents with a family history of retinoblastoma should
      be examined by a qualified ophthalmologist immediately after birth in order to
      detect and treat this condition as early as possible.

PMID- 8271854
TI  - Severe exfoliative dermatitis associated with hand ischemia during cisplatin
      therapy.
AB  - BACKGROUND: Platinum is one of the most widely used agents in clinical oncology
      today. Serious toxic effects are well recognized. FINDINGS: To our knowledge, the
      current report describes the first case of severe allergic exfoliative dermatitis
      associated with ischemia and necrosis of the hands in a patient who had received
      multiple doses of this agent. We postulate that the tissue damage was caused by
      vasospasm of small vessels from the initial injury triggered by platinum or its
      associated immune complexes. CONCLUSION: Platinum has become an integral part of
      combination chemotherapy for various solid tumors. Clinicians must recognize its
      toxic side effects and control them within tolerable limits.

PMID- 8271855
TI  - Spinal dural arteriovenous fistula causing progressive myelopathy: clinical and
      imaging considerations.

PMID- 8271856
TI  - The cost of an open infarct-related artery: comparison of treatment modalities in
      the reperfusion era.

PMID- 8271857
TI  - Iron and diabetes: an attractive hypothesis, but...

PMID- 8271858
TI  - Chandrasekhar--1983 Nobel Prize winner.

PMID- 8271859
TI  - Anaphylaxis: a potentially fatal, avoidable, and often ignored clinical problem.

PMID- 8271860
TI  - Sputum cytology.

PMID- 8271861
TI  - [Alfa-2b interferon in the treatment of thrombocytosis associated to chronic non
      leukemic myeloproliferative syndromes].
AB  - BACKGROUND: The effect of interferons in the correction of thrombocytosis in
      chronic myeloproliferative syndromes is well known. In this study the efficacy of
      alpha-2b interferon in a regimen of induction followed by a phase of sequential
      maintenance to progressively decreasing doses was evaluated with the aim of
      knowing the minimum doses necessary to maintain response. METHODS: The response
      to treatment with alpha-2b interferon was prospectively studied in a group of 37
      patients with chronic myeloproliferative syndromes with associated thrombocytosis
      (excluding chronic myeloid leukemia). Likewise, the toxicity of the treatment was
      analyzed. RESULTS: Sixty-seven percent of the patients responded (platelets lower
      than 600 x 10(9)/1) to the daily administration of 3 or 5 MU of interferon. Forty
      percent of the patients who responded to the daily schedule of administration
      maintained the response upon receiving 3 doses weekly for 4 months. Half of the 8
      patients who received 2 weekly doses of interferon for 4 months continued
      maintaining the responses. Only two of the 4 patients who received one sole
      weekly dose during the following 4 months maintained the response. Only one of
      the 37 patients who initiated treatment underwent progression of the symptoms
      present at the beginning of the study. Toxicity was high and was the cause of 12
      discontinuations of treatment (32% of the patients) during the daily treatment
      phase (9 patients) or during maintenance of 3 weekly doses (3 patients). No
      toxicity was observed in the schedule of one or two weekly doses. CONCLUSIONS:
      Alpha-2b interferon is effective in the treatment of thrombocytosis of the
      chronic myeloproliferative syndromes (excluding chronic myeloid leukemia) when
      administered daily and is ever less so when the doses are spaced at 3, 2 or 1
      week. The toxicity of interferon treatment is high when administered at affective
      doses.

PMID- 8271862
TI  - [Tendencies of mortality from cardiovascular diseases in Catalonia: 1975-1992].
AB  - BACKGROUND: There is an uncertainty of which is going to be the trend of
      cardiovascular disease in Spain. In the present study cardiovascular disease
      mortality is described from 1975 to 1992 in Catalonia, and a prediction until
      1997 is made, assuming the same trend. Possible causes of this trend are
      analyzed. METHODS: Deaths from cardiovascular disease, ischaemic heart disease
      and stroke have been identified from 1975 to 1992. It has been used the direct
      method for standardization by age and sex, using the European population as the
      standard population. Logarithmic transformations of the standardized rates were
      used for each cause of death and for both sexes. Linear regression analysis was
      used to adjust the evolution of the rates in the time period. RESULTS: There is a
      reduction of 2.6% and 2.7% by year in rates for cardiovascular diseases mortality
      for both males and females respectively, a reduction of 1.2% by year in rates for
      ischaemic heart disease in males and a reduction of 1.8% in females, and a
      reduction of 4.0% and 4.2% for stroke in males and females respectively.
      CONCLUSIONS: Trends in cardiovascular disease mortality reveal a decline for both
      males and females, mostly due to a reduction in stroke mortality; ischaemic heart
      disease mortality slightly decreased specifically during the period 1983-1992.

PMID- 8271863
TI  - [Prevalence of non-insulin dependent diabetes mellitus in Lejona (Vizcaya,
      Spain)].
AB  - BACKGROUND: Diabetes mellitus presents a high prevalence and morbimortality. The
      aim of the present study was to know the number of newly diagnosed diabetic
      patients in addition to those who present abnormal glucose tolerance and possible
      presence of associated risk factors. METHODS: This study was carried out in
      Lejona (Vizcaya) from 1984-1985. The prevalence of non insulin-dependent diabetes
      mellitus (NIDDM) and abnormal glucose tolerance (AGT) in people older than or
      equal to 30 years of age by a randomized sample stratified by pyramids of age and
      sex (n = 862). The following data were collected: age, sex, height, weight,
      medications taken, family and personal history of diabetes mellitus (DM) and
      blood pressure. A glycemia curve was made following the criteria recommended by
      the Committee of Experts of the World Health Organization (WHO). RESULTS: The
      prevalence of DM observed in the sample was of 6.4% (confidence interval of 95%:
      4.75-8.01%) of which 3.6% corresponded to unknown DM and 2.8% to known DM. The
      prevalence of AGT was 10.4% (confidence interval 95%: 8.40-12.48%). Greater
      association was observed between DM and obesity, lower height, high blood
      pressure and age over 50. CONCLUSIONS: More than half of the diabetics were
      unaware of the disease. Given the association of non insulin-dependent diabetes
      mellitus with modifiable factors (obesity, high blood pressure) control of risk
      factors would be useful with the aim of decreasing the prevalence of diabetes
      mellitus and avoid the associated chronic complications of the disease.

PMID- 8271864
TI  - [Experience of the quality program of the clinical documentation department of
      the Hospital of Galdacano].
AB  - BACKGROUND: The management of quality is a key tool to improve efficacy of
      Spanish hospitals. Hospital quality programs and those of each department/unit
      are based on self-evaluation with the principle of there being things to be
      improved and have demonstrated their efficacy. The aim of the present study was
      to demonstrate the applicability of the methodology of quality in a Department of
      Clinical Documentation. METHODS: Four indicators of quality in the quality
      program were measured in the form of indexes over 18 months in a department of
      clinical documentation of a general hospital. RESULTS: Index of filing errors:
      0.1%, index of history availability: 98%, index of histories not in place: 6.4 to
      11.1, index of reclaimable histories: 3.1 to 5.2. CONCLUSIONS: The methodology of
      quality is applicable to a department of clinical documentation with its
      development being useful in detecting problems as the first step in improving
      quality.

PMID- 8271865
TI  - [Combined therapy in HIV infection].

PMID- 8271866
TI  - [Inflammatory pseudotumor of the lymph nodes].

PMID- 8271867
TI  - [Acute pancreatitis in newly diagnosed type I diabetes mellitus with diabetic
      ketoacidosis and hypertriglyceridemia].
AB  - A 19 years old patient who presented grade D acute pancreatitis by abdominal CT
      with marked hypertriglyceridemia during a diabetic ketoacidosis (DKA) in the
      onset of a type I diabetes mellitus is described. The pancreatitis and DKA were
      resolved with the usual treatment, and the levels of triglycerides became normal
      within one week. Hyperamylasemia is frequent in DKA although of uncertain
      significance. Acute pancreatitis coinciding with DKA has been described, in this
      case radiologic findings demonstrated the diagnosis. No other bibliographic
      references have been found in which pathologic imaging in abdominal CT are
      described in a situation of DKA with hyperamylasemia. Moderate
      hypertriglyceridemia is common upon initiation of diabetes mellitus and likewise
      it usually presents during the course of acute pancreatitis. Pancreatitis could
      be secondary to hypertriglyceridemia and the latter to the insulin deficiency.

PMID- 8271868
TI  - [Science on turbulent waters].

PMID- 8271869
TI  - [Absence of interaction between oral anticoagulants and influenza vaccine].

PMID- 8271870
TI  - [Seroprevalence of infection by human type 6 herpes virus in patients with the
      human immunodeficiency virus infection].

PMID- 8271871
TI  - [Thrombophlebitis migrans as the first symptom of a myelodysplastic syndrome].

PMID- 8271872
TI  - [Aneurysm of the interatrial septum and cerebral infarctions].

PMID- 8271873
TI  - [Endocarditis due to Q fever].

PMID- 8271874
TI  - [Validity of a rapid method for identifying Escherichia coli and Proteeae in
      urine].

PMID- 8271875
TI  - [The greatness of family physicians--and their decline?].

PMID- 8271877
TI  - [Are principles of ethics observed in new discoveries on diabetes?].

PMID- 8271876
TI  - [An economic strait-jacket is not good for health care].

PMID- 8271878
TI  - [What should the education of assistants in physiology be?].

PMID- 8271879
TI  - [Ethics among physicians in former Yugoslavia are to be questioned].

PMID- 8271881
TI  - [Patient or customer?].

PMID- 8271880
TI  - [Further support for steroids in bacterial meningitis].

PMID- 8271882
TI  - [Unnecessary painful tests for whooping cough vaccines].

PMID- 8271883
TI  - [Uterine curettage. Is it necessary in the future?].

PMID- 8271884
TI  - [Psychiatric vocational rehabilitation. An important but neglected activity].

PMID- 8271885
TI  - [Thromboembolism in orthopedics. Establishment of wide preventive measures is
      necessary].

PMID- 8271886
TI  - [Gratifying results with new routines. Good time for breast feeding of infants
      treated at the neonatal units].

PMID- 8271887
TI  - [Release the self-healing resources of the patient. Comments on a "painful
      alliance"].

PMID- 8271888
TI  - [Do teenagers need play therapy? Great need of teenage-oriented hospital care].

PMID- 8271889
TI  - [Urogenital estrogen deficiency symptoms. Too few elderly women receive any
      treatment].

PMID- 8271890
TI  - [Fundus oculi photography. A good screening method for diabetic retinopathy].

PMID- 8271891
TI  - [Quality assurance for a selected population. Indications for vitamin B12
      analysis].

PMID- 8271892
TI  - [Screening of fetal abnormalities. Increasing demand for ultrasonic evaluation].

PMID- 8271893
TI  - [The Ethics Committee: ultrasonographic screening is not objectionable on ethical
      grounds].

PMID- 8271894
TI  - Magnetic resonance measurement of blood flow in peripheral vessels after acute
      exercise.
AB  - Velocity-encoded Cine magnetic resonance imaging (MRI) was used to measure blood
      flow in the anterior tibial artery (AT), posterior tibial artery (PT), and
      popliteal artery of adult human subjects (mean age 29 yr) before and after 90 s
      of ankle dorsiflexion exercise. Before exercise, mean flow, peak systolic
      velocity, and end-diastolic velocity in AT were 8.1 +/- 1.6 (SE, n = 6) ml/min,
      26.9 +/- 2.6 cm/s, and -0.6 +/- 0.4 cm/s, respectively. After exercise, mean flow
      and peak systolic velocity in AT increased by 19-fold and 3-fold, respectively,
      and end-diastolic velocity increased to 8.7 +/- 1.1 cm/s. Flow in popliteal
      artery above its bifurcation was similar to the sum of flows in AT and PT, both
      before and after exercise. Flow in AT declined exponentially after exercise with
      a mean half-time of 4 min. The results demonstrate the utility of MR phase
      encoded flow-velocity measurements for physiological studies of peripheral
      vascular dynamics after exercise.

PMID- 8271895
TI  - MRI-guided biopsy in inflammatory myopathy: initial results.
AB  - The purpose of this report is to describe our initial experience with techniques
      employing magnetic resonance imaging (MRI) to guide the choice of muscle to be
      biopsied in patients suspected of having inflammatory myopathy. Five patients
      with a clinical diagnosis of inflammatory myopathy (IM) were studied. Four were
      imaged prior to biopsy. Four had repeated examinations, either immediately
      following biopsy or to evaluate disease progression. Use of MRI to localize
      muscle lesions was associated with abnormal pathologic findings in all cases,
      including histopathologic demonstration of lymphocyte infiltration in three cases
      of idiopathic polymyositis; nonspecific myopathic changes were seen in one
      patient with probable dermatomyositis and in one patient with chronic
      inflammatory polyneuropathy and high serum creatine kinase levels (> 45,000
      IU/ml). The precise location of the area sampled by biopsy was visible in only
      one of four postbiopsy images. MRI shows promise in identifying pathologic muscle
      in patients suspected of having one of the inflammatory myopathies; however,
      further refinement of localization techniques may be needed to optimize
      histopathologic diagnoses.

PMID- 8271896
TI  - Contrast-enhanced magnetic resonance tomoangiography: a new imaging technique for
      studying thoracic great vessels.
AB  - The authors propose a new imaging approach for studying thoracic great vessels,
      using high-speed MR imaging combined with intravenous rapid bolus injection of a
      paramagnetic contrast media. The decrease of the T1 relaxation time of flowing
      blood induced by the contrast agent (Gd-DOTA) caused an increased signal
      intensity within the vessel lumen for a time period allowing multiplanar imaging
      of various vascular structures. The intraluminal signal enhancement is mainly
      related to the blood concentration of the contrast agent as in conventional X-ray
      angiography. Information on the aorta and pulmonary arteries obtained by the so
      called contrast-enhanced magnetic resonance tomoangiography appears complementary
      to that obtained with other vascular MR imaging procedures such as cine-MRI and
      magnetic resonance angiography (MRA).

PMID- 8271897
TI  - Temporal and spatial assessment of normal cerebrospinal fluid dynamics with MR
      imaging.
AB  - The purpose of this study was to measure normal cerebrospinal fluid (CSF)
      pulsations within the intracranial and upper cervical subarachnoid spaces and the
      ventricular system. Phase contrast cine MR sequences were performed in sagittal
      and axial planes on 13 volunteers with flow encoding in the craniocaudal
      direction. CSF pulsations displayed considerable variations in healthy subjects,
      depending both on measurements localization and subjects, with CSF peak
      velocities ranging from 0 to 7 cm/s. In the subarachnoid spaces, the highest
      velocities occurred in the anterior location and increased from the cerebellar
      pontine angle cisterns towards the lower cervical spaces. In the ventricular
      system, the highest velocities occurred through the aqueduct of Sylvius. CSF flow
      within the third ventricle seemed to reflect a circular motion. There was a
      caudal net CSF flow in the aqueduct whereas in the upper cervical spaces net CSF
      flow was caudal anteriorly and cranial laterally. Velocity profiles of CSF
      pulsations demonstrated arterial morphology. After the R wave, caudal systolic
      motion was first observed in the posterior subarachnoid spaces, soon after in the
      anterior subarachnoid spaces and later in the ventricular system. Considering the
      morphology of CSF pathways, three successively initiated phenomena may explain
      the temporal course of CSF motion: the systolic expansion of the main arteries at
      the base of the brain, the systolic expansion of the cerebrospinal axis and,
      finally, the systolic expansion of the choroid plexuses.

PMID- 8271898
TI  - A birdcage resonator for intracavitary MR imaging.
AB  - An intracavitary probe for magnetic resonance imaging of the pelvis has been
      developed that takes advantage of the "inside-out" spatial characteristics of a
      birdcage resonator. The probe consists of an eight-leg, birdcage resonator in a
      low-pass configuration operating in receive-only mode. The resonator circuit is
      mounted on a solid rod, is encased in Teflon, and has been used to obtain
      detailed images of pelvic anatomy in a male canine. The approximate cylindrical
      symmetry of the external sensitivity profile of this type of circuit, employed in
      an intracavitary application, demonstrates the potential superiority of this type
      of probe design over single-loop intracavitary coils. Axial, coronal, and
      sagittal MR images, obtained with 8 and 16 cm fields of view, are presented to
      illustrate the advantages of this type of intracavitary probe compared with
      conventional body-coil images. The prototype described in this report has been
      designed for clinical use in human subjects and is currently undergoing testing
      to determine its efficacy in the evaluation of rectal, prostate, and gynecologic
      pathology.

PMID- 8271899
TI  - Flow field mapping by multi-zone adiabatic passage excitation.
AB  - This paper describes a robust method for flow field mapping by multi-zone
      adiabatic fast passage (AFP). It provides a quick and simple way to
      simultaneously acquire flow profiles at several locations and arbitrary
      orientations inside the field-of-view. The flow profile is the time-averaged
      evolution of the labeled flowing material. Results obtained using a carotid
      bifurcation and jet phantoms are similar to the previous experimental studies
      employing Laser Doppler Anemometry (LDA), and other flow visualization
      techniques. In addition, the preliminary results obtained with a human volunteer
      support the feasibility of the technique for in vivo flow quantification.

PMID- 8271900
TI  - Superparamagnetic iron oxide particles and positive enhancement for myocardial
      perfusion studies assessed by subsecond T1-weighted MRI.
AB  - Superparamagnetic iron oxide particles (SPIOs) are usually referred to as T2 MR
      contrast agents, reducing signal intensity (SI) on T2-weighted MR images
      (negative enhancement). This study reports the original use of SPIOs as T1
      enhancing contrast agents, primarily assessed in vitro, and then applied to an in
      vivo investigation of a myocardial perfusion defect. Using a strongly T1-weighted
      subsecond MR sequence with SPIOs intravenous (IV) bolus injection, MR imaging of
      myocardial vascularization after reperfusion was performed, on a dog model of
      coronary occlusion followed by reperfusion. Immediately after the intravenous
      bolus injection of 20 mumol/kg of SPIOs, a positive signal intensity enhancement
      was observed respectively, in the right and left ventricular cavity and in the
      nonischemic left myocardium. Moreover, compared to normal myocardium, the
      remaining ischemic myocardial region (anterior wall of the left ventricle)
      appeared as a lower and delayed SI enhancing area (cold spot). Mean peak SIE in
      the nonischemic myocardium (posterior wall) was significantly higher than in the
      ischemic myocardium (anterior wall) (110 +/- 23% vs. 74 +/- 22%, Mann-Whitney
      test alpha < 1%, n1 = 6, n2-n1 = 0, U > 2). In conclusion, the T1 effect of SPIOs
      at low dose, during their first intravascular distribution, suggests their
      potential use as positive markers to investigate the regional myocardial blood
      flow and some perfusion defects such as the "no-reflow phenomenon."

PMID- 8271901
TI  - Quantitative cerebral magnetic resonance imaging during ACTH treatment of
      multiple sclerosis.
AB  - Serial MR scans were performed with the 2DFT imaging method and the filtered
      backprojection imaging method on 12 patients with multiple sclerosis in acute
      phase, 4 in a relapsing/remitting form, and 8 in a progressive form, before,
      during and after ACTH treatment. Both T1 and T2mono relaxation times, obtained by
      fitting transverse magnetization decay curves with a monoexponential function
      within the apparently normal white matter and the areas of increased signal, were
      measured. With the backprojection method it was possible to fit the transverse
      magnetization decay curve with a biexponential function and obtain T2long and
      T2short relaxation times. The T2mono and T1 relaxation times of the apparently
      normal white matter were significantly different from those obtained for
      volunteers, but no significant differences were found before, during, or after
      treatment. The transverse magnetization decay curves of the areas of increased
      signal were better fitted by a biexponential function. No significant changes in
      these relaxation times were observed after ACTH treatment. These results argue
      against an anti-oedematous action of ACTH and may suggest that it has an
      immunosuppressant effect.

PMID- 8271902
TI  - MRI-monitored cryosurgery in the rabbit brain.
AB  - The inability to observe the transient, irregular shape of the frozen region that
      develops during cryosurgery has inhibited the application of this surgical
      technique to the treatment of tumors in the brain and deep in visceral organs. We
      used proton NMR spin-echo and spoiled gradient-echo imaging to monitor the
      development of frozen lesions during cryosurgery in the rabbit brain and the
      resulting postcryosurgical changes up to 4 hr after freezing. Spoiled gradient
      echo images (TE = 14 ms; TR = 50 ms) were acquired during freezing and thawing at
      a rate of 15 s/slice. Although the frozen region itself is invisible in MR
      images, its presence is distinguished easily from the surrounding unfrozen soft
      tissue because of the large contrast difference between frozen and unfrozen
      regions. T2-weighted spin-echo images (TE = 100 ms, TR = 2 s) obtained after
      thawing suggest that edema forms first at the margin of the region that was
      frozen (cryolesion) and then moves into the region's core. Histological
      examination showed complete necrosis in the cryolesion and a sharp transition to
      undamaged tissue at the margin of the lesion and its image. Blood-brain barrier
      (BBB) damage was investigated using gadolinium-DTPA. The region of edema in the
      T2-weighted spin-echo images was coincident with the area of BBB damage in the Gd
      DTPA-enhanced T1-weighted spin-echo images (TE = 33 ms, TR = 400 ms) and both
      were distinguishable as areas of high signal relative to the surrounding normal
      tissue. The results of these experiments indicate that MR can both effectively
      monitor the cryosurgical freezing and thawing cycle and characterize the
      postcryosurgical changes in tissue during follow-up.

PMID- 8271903
TI  - Echo planar imaging of perfluorocarbons.
AB  - Emulsions of perfluorotributylamine (FTBA) and perflubron were evaluated for
      their utility in 19F echo planar imaging. Fluorine images of the emulsions were
      obtained in a phantom and two mice that had been predosed. Both agents, but
      particularly perflubron, show potential for fluorine echo planar studies because
      of the long spin-spin relaxation times of the CF3 resonances. High resolution
      thin slice images obtained in as little as 26.6 ms are presented.

PMID- 8271904
TI  - NMR microimaging studies of water diffusivity in saturated, microporous systems.
AB  - A novel microimaging method is described for measuring the effective diffusion
      coefficient (D infinity) of water in saturated, microporous materials. A simple
      multicompartment computer simulation was used to show how the value of D
      infinity, when combined with measurements of water proton relaxation times and
      pulsed field gradient spin-echo amplitudes, allows the pore size distribution and
      pore connectivity to be characterized.

PMID- 8271905
TI  - MRI measurements of the dependence on T1 of the echo amplitudes using a multiple
      spin-echo scheme.
AB  - Analytical calculations using the Bloch formalism were performed to assess the
      dependence on T1 of the echo amplitudes for the Phase-Alternating Phase-Shift
      (PHAPS) multiple spin-echo protocol. Measurements in a 0.5 T MR imaging unit were
      performed to ratify the analytical results. Especially for low T2 values, the
      echo amplitudes were erroneous, with an increasing contribution from stimulated
      echo components with increasing T1. Apart from affecting T2 estimates, stimulated
      echoes generated a non-monoexponential signal decay of the echo trains. The
      results confirmed previous simulation studies as regards the dependence on T1 of
      T2 estimates from PHAPS.

PMID- 8271906
TI  - Selective 19F MR imaging of 5-fluorouracil and alpha-fluoro-beta-alanine.
AB  - A 19F MR chemical shift imaging (CSI) technique is presented which enables
      selective imaging of the antineoplastic drug 5-fluorouracil (5-FU) and its major
      catabolite alpha-fluoro-beta-alanine (FBAL). The CSI sequence employs a chemical
      shift selective (CHESS) saturation pulse to suppress either the 5-FU or the FBAL
      resonance before the other component of the two-line 19F MR spectrum is measured.
      Because the transmitter frequency can always be set to the Larmor frequency of
      the 19F resonance to be imaged, this approach yields 5-FU and FBAL MR images free
      of chemical shift artifacts in read-out and slice-selection direction. In phantom
      experiments, selective 5-FU and FBAL images with a spatial resolution of 15 x 15
      x 20 mm3 (4.5 ml) were obtained in 30 min from a model solution, whose drug and
      catabolite concentrations were similar to those estimated in the liver of tumor
      patients undergoing IV chemotherapy with 5-FU. The drug-specific MR imaging
      technique developed is, therefore, well-suited for the direct and noninvasive
      monitoring of the up-take and trapping of 5-FU in liver tumors in vivo.

PMID- 8271907
TI  - Spectral localization of arbitrarily shaped regions of interest (SLASH) using
      single voxel signals.
AB  - A method for obtaining localized spectra from arbitrarily shaped regions of
      interest is described. When a sample consists of homogeneous compartments or
      domains, spectra localized in each compartment can be obtained from signals of
      single voxels with regular shapes by solving a set of simultaneous linear
      equations. Experimental demonstrations on a phantom and on human brain in vivo
      for a two compartment, two voxel case are presented. The issue of signal-to-noise
      ratio is also discussed.

PMID- 8271908
TI  - Alzheimer's disease histologically proven studied by MRI and MRS: two cases.
AB  - Two patients affected by severe Alzheimer's disease (AD) were investigated by MRI
      and image-guided 31P MRS. In one case, 1H MRS was additionally performed. In both
      cases the diagnosis of AD was confirmed, post mortem, by the pathologist. The
      spectral parameters of the 31P MR spectra were estimated by fitting the 31P MR
      signals in the time domain. Our 31P MRS results suggest that it is possible to
      detect the membrane catabolism, as indexed with the level of PDE resonances
      visible in in vivo 31P MRS, at least in severe AD cases. The 1H spectrum from AD
      brain showed a marked decrease of NAA signal respect to choline.

PMID- 8271909
TI  - Rare case of double aortic arch with hypoplastic right dorsal segment and
      associated tetralogy of Fallot: MR findings.
AB  - We report a rare case of double aortic arch with a hypoplastic right dorsal arch
      segment, which was also associated with tetralogy of Fallot. Accurate
      characterization of the hypoplastic right arch segment by MRI preoperatively
      determined the optimal surgical approach to releasing the symptomatic vascular
      ring. MRI was also useful in assessing and monitoring associated tracheomalacia.

PMID- 8271910
TI  - Detection of mycotic pseudoaneurysm of the ascending aorta using MRI.
AB  - Mycotic pseudoaneurysms of the ascending aorta are rare cardiovascular lesions
      that carry the risk of potentially disastrous complications such as aortic
      rupture or widespread sepsis. Regardless of its location in the arterial system,
      this lesion carries a high mortality rate. Early diagnosis of mycotic
      pseudoaneurysm is paramount for optimizing the chances of surgical therapy. While
      imaging strategies of this lesion have included aortography, echocardiography,
      and computed tomography, the information gained from each of these individual
      studies may be acquired in a single MR imaging session. MRI offers the
      fundamental advantages of noninvasiveness, nonionization, and multiplanar imaging
      capabilities. Additionally, MRI provides excellent soft tissue contrast, a wide
      field of view, qualitative and quantitative flow analysis, and an independence of
      operator expertise or patient body habitus.

PMID- 8271911
TI  - Retrocrural masses of extramedullary hemopoiesis in beta-thalassemia.
AB  - A case of extramedullary hemopoiesis in an 18-yr-old girl suffering from beta
      thalassemia is reported. Extramedullary hemopoietic masses were localized apart
      from the paraspinal region in the retrocrural areas as well as the presacral
      region associated with massive destruction of the sacrum. The importance of
      recognition of hemopoietic masses in these regions in conditions other than
      hereditary hemolytic anaemias is briefly discussed.

PMID- 8271912
TI  - Indications for induction of labor.
AB  - Despite all the new technology, the research being conducted, and progress in the
      field of obstetrics, much controversy remains concerning the management of the
      high-risk patient and when--or whether--to induce labor. One factor complicating
      the discussion is that health centers vary in the services they offer. Many are
      small, lacking a high-risk labor and delivery unit, a fetal assessment unit, and
      a neonatal intensive care unit, and may be far from larger centers. Early
      diagnosis of a complicated pregnancy not only means early treatment by the
      admitting hospital, but, if necessary, crucial time to transfer the patient to
      appropriate facilities. All the following play a major role in obstetrical care
      nursing: participating in the diagnosis that indicates the need for induction,
      implementing and following through with the various methods of induction, and at
      the same time, providing emotional support to patients. Early prenatal counseling
      and education, ongoing alertness to variations in maternal/fetal conditions,
      accurate interpretation and recording of data, and open patient/nurse/physician
      communication are all important factors in a successful birth, with healthy
      mother and infant.

PMID- 8271913
TI  - Prostaglandin E2 for cervical ripening.

PMID- 8271914
TI  - Prostaglandin E2. Its role in preinduction cervical ripening, and its clinical
      use in obstetrics today. Introduction.

PMID- 8271915
TI  - Initiation of parturition.

PMID- 8271916
TI  - Proportion of protein A bindable molecules in human IgM and IgA antibodies to
      seven antigens.
AB  - Human IgM or IgA antibodies to seven antigens (tetanus and diphtheria toxoids,
      and five bacterial polysaccharides) were studied by determining what proportion
      of these antibodies were bound by staphylococcal protein A. This alternative
      binding is a marker of VH genes of family 3. Each response was studied in an
      average of nine individuals. The binding proportion of antibodies to the two
      toxoids resembled that of total serum immunoglobulins; 13-14% of IgA and 40% of
      IgM antibodies were bound by protein A. All anti-polysaccharide antibodies had
      higher proportions of protein A bindable molecules than serum IgM or IgA
      indicating a bias for VH genes. This excess was high in antibodies to Haemophilus
      influenzae type b (Hib) and pneumococcal type 14 polysaccharides (> two-fold). It
      was moderate but statistically significant in antibodies to pneumococcal types
      18C and 3 capsular polysaccharides and to C polysaccharide. All vaccinated Finns
      exhibited the VH3-preference in antibodies to Hib and type 14 polysaccharide.

PMID- 8271917
TI  - Characterization of non-toxic mutant toxins of Vero toxin 1 that were constructed
      by replacing amino acids in the A subunit.
AB  - Three mutant toxins of Vero toxin 1 (VT1) produced by Escherichia coli strains
      carrying mutant VT1 genes that were constructed by oligonucleotide-directed site
      specific mutagenesis were purified to homogeneity. They are E167Q (glutamic acid
      at position 167 from the N-terminus of the A subunit was replaced by glutamine),
      R170L (arginine at position 170 from the N-terminus of the A subunit was replaced
      by leucine) and E167Q-R170L (glutamic acid at position 167 and arginine at
      position 170 were replaced by glutamine and leucine, respectively). The purified
      E167Q and E167Q-R170L had markedly decreased activities, such as inhibition of
      protein synthesis, cytotoxicity to Vero cells and mouse lethality. The decrease
      in the R170L activities was less than those of the other two mutant VT1s. Neither
      additive nor synergistic decreases of the activities were observed in the double
      mutant E167Q-R170L in which two amino acids were replaced. Ouchterlony double gel
      diffusion showed that antiserum against the purified E167Q-R170L gave a line of
      identity between mutant VT1s and VT1. Moreover, anti-E167Q-R170L antiserum showed
      similar activity to that of anti-VT1 antiserum in neutralizing the Vero cell
      cytotoxicity and mouse lethality of VT1. The data suggest that these mutant VT1s,
      especially E167Q and E167Q-R170L, may be candidate toxoids that protect against
      diseases caused by Verocytotoxin-producing E. coli.

PMID- 8271918
TI  - Lack of pathotype specific gene in human Coxiella burnetii isolates.
AB  - Human Q fever, due to the obligate intracellular bacterium Coxiella burnetii may
      be acute or chronic. The acute form is rarely fatal, although the chronic form,
      mostly represented by chronic Q fever endocarditis, is severe and usually fatal
      in lack of appropriate treatment. A correlation between the human disease state
      and plasmid types has been described, and specific DNA sequences unique to each
      plasmid type and which would code for specific pathotypes have been
      characterized. Because this gene specificity of the pathogenesis was hypothesized
      only on a small number of isolates, we evaluated seven reference isolates and 30
      recent C. burnetii isolates from France for which all clinical data were
      available using the polymerase chain reaction by employing two specific primer
      sets. Our studies indicate that the previously described CbhE' plasmid-gene is
      not unique to C. burnetii isolates associated with acute disease, which would
      mean that the hypothesis of the correlation between gene specificity and
      pathotype has to be revised.

PMID- 8271919
TI  - Proteinase K-sensitive and filterable phagosome-lysosome fusion inhibiting factor
      in Afipia felis.
AB  - Afipia felis is one of the putative agents of cat scratch disease (CSD). Its
      intracellular location was previously demonstrated in tissue sections. It has
      been recently grown in human monocytes and in HeLa cells. We report that A. felis
      may infect human macrophages and the P 388 D1 murine macrophage cell line, yet is
      unable to grow in the cell-free culture medium. In both human macrophages and P
      388 D1, the organisms multiply in a vacuole after active inhibition of phagosome
      lysosome fusion (P-L) as demonstrated with cationized ferritin-labeled lysosomes.
      This P-L fusion inhibition is diffusable and is due to a filterable factor which
      is inactivated by protease digestion. The pathogenic role of A. felis in CSD may
      result from its ability to invade and multiply in macrophages.

PMID- 8271920
TI  - Identification of Bordetella avium using the polymerase chain reaction.
AB  - A DNA fragment from Bordetella pertussis, encoding the fim2 fimbrial subunit gene
      with adjacent sequences, was used as a probe for the detection of homologous
      sequences in chromosomal DNA of Bordetella avium. A 1.8 kb Sa1I-PstI fragment
      from the genome of B. avium, which hybridized with the probe, was isolated and
      sequenced. No fimbrial subunit gene was located on the B. avium DNA fragment. Two
      regions could be distinguished in the sequence of the fragment. Region 1, which
      was 80% identical to the sequence upstream of the fim2 gene of B. pertussis and
      region 2, which had no identity with any known sequence. A 491 bp EagI DNA
      fragment (probe A) within region 1 and a 650 bp EagI DNA fragment (probe B)
      within region 2 were used as DNA probes on restriction endonuclease digests of
      chromosomal DNA from various bacterial species. This hybridization experiment
      showed that the region 2 sequence was specific for B. avium. A polymerase chain
      reaction (PCR) with specific primers within region 2 resulted in the
      amplification of a 500 bp DNA fragment with B. avium DNA only. This PCR is a
      useful method for the rapid detection of B. avium and appeared useful to
      discriminate B. avium from other Bordetella species and also from Alcaligenes
      faecalis.

PMID- 8271921
TI  - Staphylococcus hyicus-skin reactions in piglets caused by crude extracellular
      products and by partially purified exfoliative toxin.
AB  - Staphylococcus hyicus may cause a spontaneous generalized exudative epidermitis
      in piglets. The progression and regression of macroscopical and histopathological
      lesions in piglet skin after subcutaneous injection of sterile concentrated
      culture supernatant (CCS) from one virulent and one avirulent strain of S. hyicus
      was studied every 24 h until 144 h post-injection. CCS from the virulent strain
      caused local alterations of the epidermis comparable to those of spontaneous
      exudative epidermitis: exfoliation, crust formation, exocytosis, formation of
      vesicles, and pustules and acanthosis. CCS from the avirulent strain only caused
      a transient erythema of the skin and no histopathological alterations of the
      epidermis. Additionally, proteins in CCS from the virulent strain were
      fractionated by column chromatography. Skin reactions similar to those caused by
      CCS from the virulent strain were induced by one fraction of proteins that
      contained eight protein bands in SDS-PAGE analysis. Two of these protein bands,
      with molecular weights of approximately 27 kDa and 30 kDa, were unique to the
      virulent strain compared to the avirulent strain. The results of this study
      indicate that one of these two proteins or both is a heat-labile exfoliative
      toxin, and that the toxin is a significant factor in the pathogenesis of
      exudative epidermitis in piglets.

PMID- 8271922
TI  - Immunization with fibronectin binding protein from Staphylococcus aureus protects
      against experimental endocarditis in rats.
AB  - Rats were immunized with a fusion protein (gal-FnBP) encompassing beta
      galactosidase and the domains of fibronectin binding protein from Staphylococcus
      aureus responsible for binding to fibronectin. Antibodies against gal-FnBP were
      shown to block the binding of S. aureus to immobilized fibronectin in vitro.
      Endocarditis in immunized and non-immunized control rats was induced by
      catheterization via the right carotid artery, resulting in damaged aortic heart
      valves which became covered by fibrinogen and fibronectin. The catheterized rats
      were then infected intravenously with 1 x 10(5) cells of S. aureus. The number of
      bacteria associated with aortic valves was determined 1 1/2 days after the
      challenge infection and a significant difference in bacterial numbers between
      immunized and non-immunized groups was then observed (p < 0.05).

PMID- 8271923
TI  - The 90 kilobase pair virulence plasmid of Salmonella serovar Typhimurium coexists
      in strains with a plasmid of the 23 incompatibility groups.
AB  - Strains containing the 90 kilobase pair (kb) virulence plasmid of Salmonella ser
      Typhimurium or a cointegrate of which a part was the 90 kb plasmid were mated
      with strains harboring the plasmid of the 23 known incompatibility groups.
      Transconjugants, selected for the incoming plasmids, were isolated and purified,
      and their plasmid content was examined by agarose gel electrophoresis. The 90 kb
      plasmid can coexist for at least 54 generations with all the 23 plasmids of the
      known incompatibility groups tested.

PMID- 8271924
TI  - Vascular complications of vascularized composite tissue transfer: outcome and
      salvage techniques.
AB  - Two hundred fifty-two vascularized composite tissue transfers were performed from
      1985 to 1992 at Nara Medical University Hospital. Free tissue transfers were
      performed in 185 patients and island tissue transfers in 67 patients. Of these,
      39 flaps were reexplored because of vascular complications. On initial
      reexploration, vascular obstruction was found at the site of anastomosis or in
      the main vascular pedicle in 36 patients and in the perforating vessels to the
      monitor flap in three patients. Arterial thrombus occurred in 11 patients, venous
      thrombosis in 12, and both in nine. Twenty-five reexplored flaps were salvaged.
      Initially, heparin was administered systemically when vascular compromise was
      suspected intraoperatively or postoperatively. Recently, we have used a
      "continuous local heparinization" technique to minimize blood loss. This method
      has been used in 12 patients who underwent reexploration and in nine patients in
      whom vascular compromise was suspected. Nineteen flaps survived completely, and
      two flaps failed.

PMID- 8271925
TI  - Further clinical use of the interposition arteriovenous loop graft in free tissue
      transfers.
AB  - The use of an arteriovenous fistula (AVF) to afford vascular access for free
      tissue transfer is described in 11 consecutive patients from a 1 year period. The
      leg was the site of pathology in six cases, and a reversed saphenous AVF to the
      femoral vessels was created. In the remaining five cases, those in the head and
      neck and arm regions, the recipient vessels varied. The mean patient age was 37.7
      years, and ten of 11 patients were male. Etiologies of defect were automobile
      accidents in six cases, neoplasm in three, and gunshot wound and electrical
      injury in one patient each. Mean ischemia time was 113 +/- 15 min. Mean length of
      AVF was 27.3 +/- 2.1 cm. All flaps survived. AVF was a useful technique in the
      current study. Several maneuvers were undertaken to minimize the risk of
      thrombosis. All patients were given aspirin prior to AVF creation. Patients
      received dextran 40 in the postanastomosis period for 5 days. Finally, every
      effort was made to create the AVF between large vessels, especially in the leg,
      to maximize blood flow.

PMID- 8271926
TI  - The cephalic vein in microsurgery.
AB  - A working knowledge of the venous anatomy is seldom emphasized but is an
      essential element in all microvascular procedures. The cephalic vein has been
      chosen here to serve as a model, since it is an important source for both
      afferent and efferent flow for flap transfers as well as in limb replantations.
      The better known, lower extremity superficial veins, especially as a source for
      long vein grafts, are not necessarily the best option. The cephalic vein
      represents the most versatile of the large superficial veins of the upper
      extremity and has numerous roles in microsurgery other than as a viable
      alternative for vein grafts.

PMID- 8271927
TI  - New skeletal muscle model for the longitudinal study of alterations in
      microcirculation following contusion and cryotherapy.
AB  - This preliminary report describes the use of a rat model developed to study in
      vivo the effect of anesthesia, contusion, and cryotherapy on skeletal muscle
      microcirculation by use of an implanted chamber. The diameters of arterioles and
      venules within the chamber were determined by photomicroscopy in the contusion
      study and by compound videomicroscopy in the anesthesia study; microvascular
      perfusion was determined by laser Doppler fluxmetry (LDF). Combined ketamine and
      xylazine anesthesia significantly reduced (P < 0.05) arteriolar and venular
      diameters by 32.4% and 37.8%, respectively, and average LDF measurements by
      36.1%. Contusion significantly increased arteriolar diameters over baseline
      values (P < 0.05); cryotherapy did not alter arteriolar diameters but increased
      venular diameters (P < 0.05). It is hypothesized that this increase in venular
      diameter may, by increasing the surface area available for reabsorption, explain
      one mechanism by which cryotherapy decreases the edema of contusion. Use of this
      model should help to advance the understanding of microcirculatory dynamics
      following contusion and cryotherapy.

PMID- 8271928
TI  - Effect of denervation on endothelium-derived relaxing factor-dependent relaxation
      in the rat cremaster muscle.
AB  - Endothelium-derived relaxation mediated primarily by endothelium-derived relaxing
      factor/nitric oxide (EDRF/NO) is essential in the maintenance of vascular tone.
      However, little is known about the effects of denervation on EDRF-mediated
      relaxation in the microcirculation after reimplantation. Using intravital
      videomicroscopy in the rat cremaster model, this study assessed the effect of
      acute and chronic denervation of the muscle, produced by severing the
      genitofemoral nerve, on EDRF-mediated vasorelaxation. The results demonstrated
      that acetylcholine-induced EDRF relaxation (10(-6)M) significantly relieved
      norepinephrine-induced vasoconstriction in small arteries (40-80 microns
      diameter) in both the acute and chronic denervated muscles. There was no
      significant difference in the relaxant response between the denervated or
      innervated controls in each group or between the acute or chronic groups. This
      relaxation was prevented by methylene blue (10(-4) M). These findings suggest
      that EDRF-mediated relaxation in the microcirculation is not dependent on tissue
      innervation. Thus the use of potent endothelial dependent agonists may be of use
      in cases of vasospasm postreimplantation.

PMID- 8271929
TI  - Effect of hypertension on arterial structure and wound repair at the
      microvascular anastomosis site using stroke-prone spontaneously hypertensive rats
      (SHRSP).
AB  - Different processes of microvascular wound healing under hypertension in
      comparison to normotension have been suspected. To explore these differences at
      the site of anastomotic wound repair, we performed microvascular anastomoses of
      the femoral arteries in 12-week-old, stroke-prone hypertensive rats (SHRSP) whose
      maximum blood pressure reached 238 mm Hg and in normotensive age-matched Wistar
      Kyoto (WKY) rats. Morphologic changes under hypertension were examined via light
      microscopy. The arrangement and number of endothelial cells were examined using
      the en face silver staining technique. The plasma activity levels of factor XIII
      were also measured in each group. Transitional healing at the microvascular
      anastomosis site was evaluated via scanning electron microscopy. The extent of
      endothelial migration over the exposed media around the needle holes was
      determined using a computerized graphic analysis system. Histologic cross
      sections demonstrated a thickened media, with altered shape and arrangement of
      the smooth muscle cell nuclei in SHRSP arteries compared with WKY arteries. En
      face silver staining showed small and spindle-shaped endothelial cells with an
      irregular cell arrangement and distribution in SHRSP arteries relative to WKY
      arteries. Factor XIII was increased 36% over baseline in SHRSP rats
      postoperatively; this was significantly higher than the increase in WKY rats (P <
      0.05). Although both SHRSP and WKY arteries had similar wound healing responses
      to microvascular anastomosis, endothelial cell migration over the exposed media
      was significantly accelerated in the SHRSP rats.

PMID- 8271930
TI  - Long-term evaluation of nerve regeneration in a biodegradable nerve guide.
AB  - Nerve regeneration using artificial biodegradable conduits is of increasing
      interest. The aim of this study is to evaluate the regeneration and maturation of
      a nerve after long-term implantation (2 years) of a biodegradable poly-L
      lactide/poly-epsilon-caprolactone (PLLA/PCL) copolymeric nerve guide in the
      sciatic nerve of the rat. After harvesting, we evaluated both the regenerated
      nerves and the controls, using light microscopy, transmission electron
      microscopy, and morphometric techniques. Remnants of biomaterial were still
      present after 2 years of implantation, but the foreign body reaction was very
      mild at this stage, due to the rounded shapes of the polymer debris. Morphometric
      analysis showed significant differences between the regenerated nerve and the
      normal sciatic nerve: the number of myelinated fibers is higher, and the mean
      fiber diameter of the myelinated fibers in the regenerated nerve is smaller. In
      conclusion, the results demonstrate that the new PLLA/PCL nerve guide can provide
      optimal conditions for regeneration and maturation of damaged nerves.

PMID- 8271931
TI  - Fiber regeneration in nerve grafts without connection to a target muscle: an
      experimental study in rabbits.
AB  - In 30 rabbits, both saphenous nerves were harvested as autografts and coapted to
      the branch for the rectus femoris muscle without connection to any distal target
      muscle. The graft from the right thigh was led to the contralateral extremity
      (crossover grafting). The graft on the left side remained on the same extremity
      (ipsilateral grafting). Animals were separated into four groups and were
      sacrificed 3, 6, 9, and 12 months after grafting. Specimens of the grafts and the
      donor motor branches were harvested for histomorphometric examination. The number
      of myelinated nerve fibers in the distal end of the nerve grafts was
      significantly increasing from 3 to 6 months after grafting and remained on a
      relatively constant level in the long-term groups. Three months after the first
      operation, greater numbers of myelinated nerve fibers were counted after
      ipsilateral grafting than after crossover grafting. In the long-term groups, this
      difference could not be observed.

PMID- 8271932
TI  - Results of vascularized joint allograft under immunosuppression with
      cyclosporine.
AB  - The effects of cyclosporine (CsA), a strong immunosuppressive drug, on
      vascularized allogeneic joint transplantations were examined. An orthotopical
      transplant model of a vascularized knee joint allograft was developed using
      inbred DA and Lewis rats to investigate the fate of grafts following withdrawal
      of short-term immunosuppression compared to continuous immunosuppression with
      CsA. Five isograft controls acquired solid bone union at both femur and tibia
      sites within 4 weeks, and joint function as skeletal support was maintained until
      25 weeks. Without immunosuppression, ten allografts were severely rejected within
      the first week, and joint destruction occurred immediately. Twenty-five short
      term immunosuppressed rats acquired solid union, but, after withdrawal of
      immunosuppression, grafted joints showed gradual rejection and were destroyed due
      to pathological fractures or joint instability, although partial
      revascularization from the recipient occurred. Ten allografts under continuous
      immunosuppression at a dose of 10 mg/kg/day showed no rejection and remained
      viable for 12 weeks postoperatively, but thereafter all rats died. Death was
      considered to be a side effect of CsA. Fifteen animals, under continuous
      immunosuppression at a dose of 5 mg/kg/day, showed no rejection except in the
      bone marrow; the grafted joint function was not effected until 25 weeks.
      Continuous treatment with low and nontoxic doses (5 mg/kg/day) of CsA was
      necessary to maintain the functions of the grafted joint.

PMID- 8271933
TI  - UW solution as an experimental microvascular skin flap perfusate.
AB  - UW solution has been found to be an effective organ perfusate for
      transplantation. Initial studies in experimental pedicle skin flaps have also
      demonstrated its unique effectiveness in prolonged ischemia. To understand better
      the limits of its preservation properties without the influence of endothelial
      clamp damage, we have undertaken to study the properties of UW solution in
      experimental microvascular free flaps. Control, lactated Ringer's, and UW
      solutions were utilized in pedicle and microvascular free flaps in Sprague-Dawley
      rats over varying periods of ischemia. UW solution demonstrated a clear
      superiority over all other solutions in both flap models. In addition there also
      was a significant prolongation of critical ischemia time in UW-treated free flaps
      compared to pedicle flaps.

PMID- 8271934
TI  - Protocol for the technique of orthotopic liver transplantation in the rat.
AB  - Orthotopic rat liver transplantation (OLT) has been generally accepted as an
      excellent model for the analysis of pathological, physiological, and
      immunological aspects related to organ transplantation. However, many researchers
      require a long training period to achieve a high success rate using this major
      surgical procedure on small animals. We therefore developed a protocol for
      learning rat OLT. It is recommended, initially, that the heterotopic heart
      transplantation (HHT) model be used to master the cuff technique, since this
      technique is similar to that in OLT and leads to an understanding of another
      organ transplantation technique. For beginners who advance beyond the HHT step to
      OLT but cannot finish the anhepatic phase within 30 min, we recommend the use of
      portosystemic-shunted rats as recipients. These animals have had their spleens
      transposed subcutaneously more than 3 weeks before use. The use of these
      modifications and this training program makes it possible to master the
      techniques and to achieve a high success rate with a short training period.

PMID- 8271935
TI  - Precision of suture placement with microscope- and loupe-assisted anastomoses.
AB  - Twenty-eight anastomoses involving seven surgeons were done on 2 mm Gortex
      vascular prostheses to test the effect of magnification on the precision of
      suture placement. One-half were done with 3.5-4x prism loupe magnification and
      the other one-half with 8-30x microscope magnification. The variability of suture
      placement (defined here as precision) was measured in a blinded fashion. The mean
      suture puncture to prosthesis edge measurement for the microscope-assisted group
      was approximately 0.03 mm closer to the edge. The variability from the mean for
      the microscope-assisted group was approximately 0.01 mm less than that for the
      loupe-assisted group. This difference was statistically significant at a P value
      of 0.0123.

PMID- 8271936
TI  - Morality and freedom: challenges to a field in transition.

PMID- 8271937
TI  - Cognitive deficits associated with fragile X syndrome.
AB  - Recent research has identified fragile X syndrome as the second leading cause of
      mental retardation. A unique profile of behavioral patterns and cognitive
      deficits associated with this disorder has gradually emerged. Current published
      literature has become repetitive with physical and clinical characteristics of
      this syndrome. Educators, however, have failed to adequately address or clarify
      learning approaches and remediation strategies that are necessary to develop
      appropriate training and educational programs. Current research on cognition
      among individuals with fragile X syndrome was reviewed and intervention
      strategies discussed that should be considered in the development of programs for
      these individuals.

PMID- 8271938
TI  - Determinants of direct-care staff turnover in group homes for individuals with
      mental retardation.
AB  - A model of direct-care human service staff turnover was proposed and tested with
      236 direct-care staff members in nine private, nonprofit New Jersey agencies. A
      path analysis of the data was conducted. Four variables were found to contribute
      to current job satisfaction: agreement of the job with personal goals and values,
      burnout, satisfaction with supervision, and employment history. In turn, current
      job satisfaction led to intention to quit, which led to actual turnover.
      Implications for the human service field and future research were explored.

PMID- 8271939
TI  - Service delivery patterns for adults with mild mental retardation at community
      mental health centers.
AB  - Results of a national survey on mental health services for adults with mild
      mental retardation sent to directors of psychological services at community
      mental health centers was discussed. In general, adults with mild mental
      retardation were less likely to receive the full array of available services.
      Individuals with mental retardation were not frequent consumers of community
      mental health services and received differential treatment at these Centers.
      Implications of these findings were discussed.

PMID- 8271940
TI  - Managed health care services for people with mental retardation: impact on
      inpatient utilization.
AB  - All admissions of people with mental retardation to a community hospital during
      one year were examined to determine the effects of a managed-care model on
      selected outcome variables. Hospitalization outcomes for patients receiving
      health care services through the program (care coordination group) were compared
      to those not enrolled (usual care group). Patients in the care coordination group
      were found to have shorter hospital stays, when adjusted for diagnosis-related
      groups; fewer readmissions; and were less severely ill upon admission. Cost data
      were extrapolated to show that costs of care coordination activities were
      partially offset by reductions in inpatient utilization.

PMID- 8271941
TI  - Implementation of an interdisciplinary psychotropic drug review process for
      community-based facilities.
AB  - A continuing psychotropic drug review process developed and implemented in 1986
      by a community-based agency serving individuals with mental retardation was
      described. This process has proven to be a feasible and effective system that has
      taken into account the practical realities of integration into the community and
      the use of community-based resources. The goals of establishing data-based
      interdisciplinary team review, utilizing concurrent alternative treatments, and
      prescribing psychotropic medication at the lowest effective dosage only to those
      individuals for whom it proves to make a positive difference have been met. For
      the residents of the agency's facilities, this process has led to a low
      psychotropic utilization rate of 17%. Dosage levels have been reduced for 75% of
      the individuals who have been prescribed psychotropic medication.

PMID- 8271942
TI  - Who is interested in careers in mental retardation and developmental
      disabilities?
AB  - In an effort to understand factors that may influence individuals to pursue
      careers in mental retardation, we asked students enrolled in a 10-week course and
      practicum experience to complete a pretest-posttest assessment of career
      interest. Results indicated that students having prior exposure to individuals
      with mental retardation reported significantly higher levels of career interest
      than did students without such experience. There were no significant changes in
      career interest from pre- to posttest. Students with a history of volunteering
      with individuals who had mental retardation comprised the largest group of
      students reporting career interest.

PMID- 8271943
TI  - Research productivity: a definition.
AB  - Defining research productivity has been difficult because of differing
      perceptions in the scientific and administrative communities. In the present
      study attitudes of national samples of scientists in a research Center and
      scientists not in a research Center were examined to determine which measures
      should be used in assessing productivity in a research center. A ranking of the
      most important and least important items of research productivity were included.

PMID- 8271944
TI  - Enhancing the consumer-family-staff relationship in adult services.
AB  - The present paper was written in an effort to improve mutual understanding among
      staff members of adult service agencies, their clients, and their clients'
      families and to encourage the implementation of procedures and practices that
      facilitate this goal. My aim was to foster strong, positive relationships among
      these groups by viewing the individual perspective of each and studying their
      interactions.

PMID- 8271945
TI  - Reducing chronic noncompliance in an individual with severe mental retardation to
      facilitate community integration.
AB  - Behavioral techniques facilitated the community integration of a young adult with
      severe mental retardation, which was jeopardized due to his noncompliance and
      severe aggression. Positive reinforcement and nonexclusionary timeout were
      employed to address noncompliance in his school and home environments. At school
      positive reinforcement was provided whenever the client walked a specified
      distance while either entering or leaving the school building without sitting
      down. If the client did sit down inappropriately, he was placed in a 5-minute
      nonexclusionary time-out. A similar procedure was carried out at home by the
      client's mother. Results showed that inappropriate sitting decreased and
      eventually reached a zero level. The program also reduced his aggression, which
      was prompted by physical carrying by others.

PMID- 8271946
TI  - Empirical study of mental health professionals' knowledge and attitudes towards
      the concept of age appropriateness.
AB  - Questionnaires on age appropriateness were completed by 100 mental health
      professionals from 10 states. In general, the respondents were familiar with the
      concept and had learned about age appropriateness from a variety of sources. Age
      appropriateness was defined in terms of chronological age rather than mental age
      or the two concepts combined. Respondents viewed it as a particularly important
      component in treatment success, especially in working with people who have
      developmental disabilities, adolescents, and young adults. Implications of these
      findings and suggestions for future research were provided.

PMID- 8271947
TI  - Proteolytic enzymes in coagulation, fibrinolysis, and complement activation.
      Introduction.

PMID- 8271948
TI  - Complement factor I and cofactors in control of complement system convertase
      enzymes.

PMID- 8271949
TI  - Streptokinase-plasmin(ogen) activator assays.

PMID- 8271950
TI  - Activation of human plasminogen by recombinant staphylokinase.

PMID- 8271951
TI  - Expression of human plasminogen cDNA in lepidopteran insect cells and analysis of
      asparagine-linked glycosylation patterns of recombinant plasminogens.

PMID- 8271952
TI  - Human alpha 2-plasmin inhibitor.

PMID- 8271953
TI  - Molecular interactions between tissue-type plasminogen activator and plasminogen.

PMID- 8271954
TI  - Cellular receptor for urokinase-type plasminogen activator: protein structure.

PMID- 8271955
TI  - Cellular receptor for urokinase-type plasminogen activator: function in cell
      surface proteolysis.

PMID- 8271956
TI  - Vampire bat salivary plasminogen activator.

PMID- 8271957
TI  - Probing structure-function relationships of tissue-type plasminogen activator by
      oligonucleotide-mediated site-specific mutagenesis.

PMID- 8271958
TI  - Lipoprotein (a): purification and kinetic analysis.

PMID- 8271959
TI  - Purification and characterization of inhibitors of blood coagulation factor Xa
      from hematophagous organisms.

PMID- 8271960
TI  - Hirudin and hirudin-based peptides.

PMID- 8271961
TI  - Limulus clotting factor C: lipopolysaccharide-sensitive serine protease zymogen.

PMID- 8271963
TI  - Properdin.

PMID- 8271962
TI  - Limulus clotting factor B.

PMID- 8271965
TI  - Limulus test for detecting bacterial endotoxins.

PMID- 8271964
TI  - Limulus proclotting enzyme.

PMID- 8271966
TI  - Snake venom hemorrhagic and nonhemorrhagic metalloendopeptidases.

PMID- 8271967
TI  - Small-scale preparation of complement components C3 and C4.

PMID- 8271968
TI  - Human complement serine proteases C1r and C1s and their proenzymes.

PMID- 8271969
TI  - Purification and properties of human factor D.

PMID- 8271970
TI  - C1 inhibitor.

PMID- 8271971
TI  - Neutrophil response to nontypable Haemophilus influenzae in respiratory
      infections.
AB  - Sputa from patients with respiratory infections by nontypable Haemophilus
      influenzae (H. influenzae) were investigated by electron microscopy. The cell
      wall of H. influenzae appeared wavy and nonwavy. In the cell wall the
      peptidoglycan layer was ill-defined. These patients had adequate IgG response in
      the serum against H. influenzae. However neither capsule nor fimbriae were found.
      Different stages of phagocytosis and destruction of the bacteria by
      polymorphonuclear neutrophils (PMN) were observed. PMNs were also found to
      phagocytose the debris. Evidences were found that the debris is formed mainly by
      the destruction of polymorphonuclear neutrophil. Extracellular lysosomes were
      also observed, which may have a role in destruction of both bacteria and host
      tissue. It was concluded that nontypable H. influenzae are nonfimbriated and
      noncapsulated during infection. Debris are the end product of PMN destruction,
      and phagocytosis of debris by PMNs has a role in the pathogenesis of chronic
      respiratory diseases.

PMID- 8271972
TI  - A factor found in aged tungstate solution enhanced the antibacterial effect of
      beta-lactams on methicillin-resistant Staphylococcus aureus.
AB  - We have found a factor (Factor T) in aged mixtures of tungstate and phosphate
      which greatly enhances the antibacterial effects of beta-lactams on both
      inducible and constitutive methicillin-resistant Staphylococcus aureus, but not
      on methicillin-susceptible S. aureus. Factor T alone did not strongly inhibit
      bacterial growth. There was no synergism of Factor T with other classes of
      antibiotics, nor with other groups of bacteria, and it reduced the efficacy of
      amino-glycosides and tetracycline. Upon preparation of Factor T, acidifying and
      heating the mixture of tungstate and phosphate resulted in a high yield and
      reproducibility, and no enhancing effect was observed when other anions such as
      sulfate or molybdate were used instead. Factor T is heat- and acid-stable but
      labile to alkalization, and is probably a complex of phosphate and tungstate.

PMID- 8271973
TI  - The structure of the chloramphenicol resistance gene on a transferable R plasmid
      from the fish pathogen, Pasteurella piscicida.
AB  - The chloramphenicol resistance gene (pp-cat) was cloned from a transferable R
      plasmid of Pasteurella piscicida, pSP9351, and the sequence of the gene was
      determined. Subcloning and deletion analysis localized the resistance gene, pp
      cat, to within a 2.3 kb HincII-BamHI fragment. The fragment as a probe hybridized
      with the type I chloramphenicol acetyltransferase (CAT) gene and did not
      hybridize to CAT types II, III, and CAT-VA. The fragment hybridized to
      transferable R plasmids encoded with resistance to chloramphenicol, which were
      detected from P. piscicida isolated in different years. Nucleotide sequences of
      the coding and flanking regions of pp-cat (2031 bp) identified an open reading
      frame coding type I CAT of a molecular mass of about 25,000 Da. Comparison
      analysis of the sequences outside the cat open reading frame showed also that pp
      cat has homology, in part, with the gene that coding for the endonuclease EcoRII
      and those that flank the cat gene derived from the Acinetobacter baumannii
      chromosome.

PMID- 8271974
TI  - Suppressive effect of liposomes containing DNA coding for diphtheria toxin A
      chain on cells transformed with bovine leukemia virus.
AB  - A recombinant plasmid which contained a gene for diphtheria toxin A-chain (DT-A)
      under the control of the long terminal repeat (LTR) of bovine leukemia virus
      (BLV) (BLV-LTR) was constructed to test a novel application of liposomes as
      antiviral agents. The promoter activity of BLV-LTR was estimated by the
      chloramphenicol acetyltransferase (CAT) assay using a plasmid which contains the
      coding sequence of CAT under the control of BLV-LTR (pBLVCAT). When BLV-infected
      cells were transfected with pBLVCAT, CAT activity was detected. BLV-uninfected
      cell lines, however, showed no detectable CAT activity. The plasmid DNA entrapped
      in liposomes was added to BLV-infected cells in culture. Syncytium formation
      induced by BLV-infected cells was effectively suppressed by the liposomes
      containing the gene for DT-A under the control of BLV-LTR. Conversely, liposomes
      containing the gene for DT-A without a promoter showed no such effect. DT-A gene
      containing liposomes with BLV-LTR did not affect formation of syncytium induced
      by bovine immunodeficiency virus. These observations indicate that BLV-infected
      cells were readily targeted on the level of gene expression. This strategy could
      be applied to the treatment of BLV-induced B-cell proliferation of cattle, and
      further to other viral/neoplastic diseases where specific gene expression is
      exerted.

PMID- 8271975
TI  - Production of monoclonal anti-idiotype antibodies which mimic an M-like protein
      of Streptococcus equi.
AB  - Rat monoclonal anti-idiotype antibodies (mAb2) were raised against two mouse
      monoclonal antibodies (mAb1), 1D10 and 2A6, with specificity for the M-like
      protein of Streptococcus equi. The capacity of the mAb2 to inhibit the binding
      between the corresponding mouse mAb1 against which the mAb2 were raised and the M
      like protein was investigated in an inhibition EIA. One of the ten mAb2 examined,
      namely 5D1 (anti-mAb1 1D10), was able to inhibit this binding. The mAb2 5D1 bound
      to the mAb1 1D10 in such a way as to completely inhibit the subsequent binding of
      the M-like protein antigen to the paratope of the mAb1 1D10. The mAb2 5D1 is
      likely to represent a true image of the M-like protein antigen and may thus be
      described as an Ab2 beta anti-idiotype antibody.

PMID- 8271976
TI  - Antigenic heterogeneity of Qa-2 antigens in C57BL/6.
AB  - The Qa-2 antigens are class I-like molecules encoded by genes mapped telomeric to
      the H-2D region on chromosome 17 in the mouse. A panel of 8 new monoclonal anti
      Qa-2 antibodies derived from a C3H.KBR anti-C3H. SW immunization was studied.
      Immunoprecipitation of 125I-labeled C57BL/6 splenocyte antigens showed that all
      of these antibodies precipitated 40 kDa molecules which could be completely
      precleared by the monoclonal antibody 20-8-4, which had previously been shown to
      crossreact with Qa-2. One of the monoclonal antibodies (1-12-1), however, was
      found not to completely preclear Qa-2 antigens precipitable by the other 7
      antibodies or by 20-8-4, suggesting the existence of at least two different
      species of Qa-2 molecules. Cell lines transfected with Q7 or Q9 genes were
      reactive with all 9 antibodies and the Qa-2 antigens expressed on surface
      membranes of these cells were completely precleared by both 20-8-4 and 1-12-1.
      Therefore, the observed heterogeneity of these molecules cannot be explained by
      an antigenic difference between the Q7 and Q9 gene products. 2D gel analyses
      showed identical pI spectra between Qa-2 molecules precipitated with 20-8-4 and 1
      12-1. In addition, all of the monoclonal antibodies reacted with labeled antigen
      preparations following treatment with Endo F or neuraminidase, indicating that
      carbohydrate moieties are probably not responsible for the antigenic difference
      between the two species of Qa-2 antigen.

PMID- 8271977
TI  - General practice and dementia. A national survey of Australian GPs.
AB  - OBJECTIVE: To find out what difficulties general practitioners (GPs) experience
      with diagnosing and managing dementia. DESIGN: Postal questionnaire to a random
      stratified sample of one in seven active Australian GPs (2182 of 14,932).
      RESULTS: 1473 GPs (67.5%) responded to the questionnaire. The results indicated
      reasonable knowledge about diagnostic features of dementia and good insight into
      common issues facing family carers. Even so, GPs had difficulties with diagnosis
      and management of dementia and wanted assessment protocols and educational
      programs. A minority of GPs regularly screened elderly patients for cognitive
      impairment but the majority relied on passive means of diagnosing dementia.
      Although generally positive about Aged Care Assessment Teams (ACATs) and Aged
      Care Community Services (ACCS), GPs expressed some concerns about these services.
      CONCLUSIONS: Recommendations arising from the survey were: development of an
      assessment protocol and a screening instrument, regular cognitive check-ups for
      patients over 75 years, educational programs, improved coordination with Aged
      Care Assessment Teams and Community Services, inventories and registers of local
      community services and residential facilities, and appropriate Medicare rebates.

PMID- 8271978
TI  - The decline in popularity of the intrauterine device. A survey of general
      practitioner attitudes and practices in New South Wales.
AB  - OBJECTIVE: To assess the attitudes and practices of general practitioners (GPs)
      in New South Wales in regard to intrauterine device (IUD) use. DESIGN: Randomised
      group comparison of 100 rural and 100 urban GPs by questionnaire. SUBJECTS: Sixty
      five rural and 66 urban general practitioners took part in the study. RESULTS:
      Almost 50% of GPs who responded to the questionnaire always discussed the IUD
      when counselling about contraception, whereas 6% never discussed IUDs. Rural GPs
      were more likely to discuss IUD use than urban GPs. In the past, 68.7% of GPs had
      inserted IUDs but only 20.6% still inserted them. Fifty per cent of GPs who did
      not currently insert IUDs felt they lacked expertise due to less demand for IUDs
      from women or inadequate training. CONCLUSION: Prevailing community attitudes
      towards intrauterine devices have resulted in fewer requests to general
      practitioners for IUDs, resulting in a lack of expertise in IUD insertion.
      Increased litigation associated with IUD use, and subsequent publicity, has
      increased the cost of medical indemnity insurance. All these factors have
      contributed to fewer GPs being prepared to insert IUDs. Australian women are
      being deprived of balanced information about the benefits and risks of IUD use
      and of the possibility of using this very effective, low-cost, low-maintenance
      method of contraception.

PMID- 8271979
TI  - Diseases caused by arboviruses--dengue haemorrhagic fever and Japanese B
      encephalitis.
AB  - Dengue haemorrhagic fever is a recent and more serious variant of dengue
      infection, causing significant mortality in children under 14 years of age in
      South-East Asia and the Western Pacific regions. Successful treatment depends on
      early recognition of the disease and careful monitoring of the development of
      shock. Japanese B encephalitis has a case fatality rate of 10%-30% in these
      regions, but may be controlled by vaccination.

PMID- 8271980
TI  - Arboviruses and disease in Australia.

PMID- 8271982
TI  - Going blind in Australia.

PMID- 8271981
TI  - Thrombolytic agents.

PMID- 8271983
TI  - Is diagnostic ultrasound safe? Current international consensus on the thermal
      mechanism.
AB  - OBJECTIVE: To describe the potential risk of heating during ultrasound
      examinations and to report the international consensus on the safety of
      ultrasound in medicine. DATA SOURCES AND DATA EXTRACTION: Literature on the
      biological effects of hyperthermia and ultrasound. CONCLUSION: The use of B-mode
      grey-scale imaging is not contra-indicated on thermal grounds. Some pulsed
      Doppler equipment has the potential to produce biologically significant
      temperature increases, specifically at interfaces between bone and soft tissue.
      Exposures resulting in temperatures less than 38.5 degrees C can be used without
      reservation.

PMID- 8271984
TI  - What's new in haematology?

PMID- 8271985
TI  - Premedication for snake antivenom.

PMID- 8271986
TI  - A retroperitoneal approach to surgery for stress incontinence using the
      laparoscope.

PMID- 8271987
TI  - Laparoscopic surgery for urinary incontinence.

PMID- 8271988
TI  - Aboriginal maternal mortality: whose problem?

PMID- 8271989
TI  - Fatal royal jelly-induced asthma.

PMID- 8271991
TI  - Flu vaccination recall database.

PMID- 8271990
TI  - "Catch up" pertussis vaccine.

PMID- 8271992
TI  - Guidelines for malaria prophylaxis.

PMID- 8271993
TI  - Genital Chlamydia trachomatis infection in Australia.

PMID- 8271994
TI  - Bacille Calmette et Guerin: its troubled path to acceptance in Britain and
      Australia.

PMID- 8271995
TI  - Carcinoma of the prostate.

PMID- 8271996
TI  - Carcinoma of the prostate.

PMID- 8271997
TI  - Chronic fatigue syndrome and the medical referee.

PMID- 8271998
TI  - Hospital based geriatric services: what are our future needs?

PMID- 8271999
TI  - [Recommendations for therapy of hypertension in general practice and treatment of
      hypertensive emergencies. German League for Control of Hypertension, Heidelberg].

PMID- 8272000
TI  - [The constipation problem: does dietary fiber help?].

PMID- 8272001
TI  - [Guarana--a natural product with high caffeine content].

PMID- 8272002
TI  - [Alzheimer's disease: irreparable damage in the brain?].

PMID- 8272003
TI  - [Increased homocysteine level--a risk factor for myocardial infarct?].

PMID- 8272004
TI  - Drugs for sexually transmitted diseases.

PMID- 8272005
TI  - Childhood anaplastic large cell lymphoma Ki-1/CD30: clinicopathologic features of
      19 cases.
AB  - The authors report their cumulative experience of 19 children with what was
      previously called malignant histiocytosis (MH) but is now considered a true
      lymphoma and termed anaplastic large cell lymphoma (ALCL). The median age at
      diagnosis was 10 years and 6 months (range 2 y, 11 m, to 15 y). There were 13
      males and 6 females. Most cases presented with fever, wasting and enlarged, often
      tender, lymph nodes. Other features were: fleeting cutaneous rashes in 7 cases;
      spontaneous regression of lymph nodes and skin lesions were seen in 5 patients.
      Bone marrow involvement was present in 3 cases, pulmonary infiltrate in 5,
      kidneys in 2, and central nervous system in none. The morphology of lymph node
      involvement was consistent with so-called MH, a description originally applied to
      sinusoidal infiltration by large "histiocytic" cells. The coexpression of
      lymphoid activation antigens Ki-1/CD 30 (18/19), epithelial membrane antigen EMA
      (18/19) and interleukin-2 receptor/CD 25 (10/10) was the unifying
      immunopathologic feature of the neoplasm. Lineage antigens were not identifiable
      in 8/19 instances (null phenotype), while 10/19 expressed a T-cell phenotype.
      None of the tumors expressed histiocytic markers. After variable, but intensive,
      combination chemotherapy, 15 children out of 18 evaluable achieved complete
      remission (CR). Among all patients, thirteen are still alive in CR (ten in first
      CR) with a median follow-up of 5 years. This evaluation in the pediatric age
      group reinforces that so-called MH is a lymphoid neoplasm, a conceptual change
      that could lead to improved understanding and therapy.

PMID- 8272006
TI  - Stereotactic external beam irradiation in previously untreated brain tumors in
      children and adolescents.
AB  - Stereotactically guided external beam irradiation may be a useful form of
      treatment for small, well-circumscribed, but surgically inaccessible, primary
      brain tumors that are either benign or of low malignant potential. Between March
      1988 and December 1991, 10 children and adolescents with previously untreated
      primary brain tumors were treated with stereotactic external beam irradiation
      (SEBI) using a linac-based dynamic technique. Eleven lesions were treated in the
      10 patients. Treatment was given using a collimator diameter of 1.5-4 cm (median
      2 cm). Single fractions of 18, 20, and 25 Gy were used for 3 lesions in 2
      patients. A fractionated schedule delivering a median dose of 42 Gy in 6
      fractions over 2 weeks was used in the remaining 8 patients. Morbidity related to
      treatment was minimal. Three patients suffered a temporary worsening of
      preexisting neurological symptoms and/or signs at 2, 5, and 5 months
      posttreatment, with subsequent recovery in all. With a median follow up post-SEBI
      of 17.5 months (range 5-47 months), improvement in neurological findings related
      to the lesion was noted for 5 treated lesions; 6 remained clinically stable.
      Seven of the 11 treated lesions improved radiologically, and only 2 showed
      evidence of progressive disease. Stereotactic external beam irradiation
      represents a potentially valuable therapeutic option for selected primary brain
      tumors in the pediatric and adolescent age group. Morbidity related to the
      treatment appears acceptable in frequency and type, and preliminary data with
      regard to response are encouraging. However, in order to assess the impact of
      such treatment on long-term tumor control and survival, further experience with a
      larger cohort of patients followed for a longer period of time will be necessary.

PMID- 8272007
TI  - False positive results in a neuroblastoma screening programme.
AB  - Twenty thousand, eight hundred and twenty-nine babies were screened for
      neuroblastoma at 6 months of age by measuring homovanillic (HVA) and
      vanillylmandelic (VMA) acid in urine and rationing these to creatinine. Using a
      "cut off" of the mean + 3 SD, 10 were found to be positive. Two were found on
      evaluation to have neuroblastoma and in the remaining 8 the raised levels of HVA
      and/or VMA returned to normal. Only one of the 8 false positive babies was
      absolutely normal, most having a chronic disorder or illness. Utilising new
      centiles which relate HVA and VMA to creatinine, only 3 of the 8 would have
      remained positive, a false positive rate of 0.01%. The false negative rate would
      have remained unchanged.

PMID- 8272008
TI  - Plasma and urine levels of methotrexate and 7-hydroxymethotrexate in children
      with ALL during maintenance therapy with weekly oral methotrexate.
AB  - A new high-performance liquid chromatographic assay was used to determine
      methotrexate (MTX) and its main metabolite, 7-hydroxymethotrexate (7-OH-MTX), in
      the plasma (n = 17) and urine (n = 14) of children (age 3-12 years) on
      maintenance therapy for acute lymphocytic leukemia (n = 14) or non-Hodgkin's
      lymphoma (n = 3). Each child received oral doses of weekly MTX (4.0-29 mg/m2) and
      daily 6-mercaptopurine (40-111 mg/m2). Plasma samples were collected daily from
      two children during the 1-week dose interval. A limited sampling strategy was
      designed, whereby 2 days of blood sampling were used in the other 15 patients.
      Morning urine samples were collected daily for 1 week following MTX intake from
      14 of the children. MTX was detectable in all plasma and urine samples for the
      entire dose interval. The main metabolite, 7-OH-MTX, could be detected in plasma
      and urine from all patients on the first day after dose intake but only in a few
      patients during the whole dose interval. Interpatient variability of MTX and 7-OH
      MTX levels was high at all points during the week. Significant correlation were
      found between the urinary MTX levels on days 2 and 7 and plasma MTX levels on day
      2 after intake. No significant correlation was found between drug levels in
      plasma or urine and liver function tests in the children showing signs of mild
      liver injury. This assay provides a tool for further studies on the role of
      pharmacokinetics for the clinical effects of weekly oral low-dose MTX given alone
      or in combination with 6-mercaptopurine.

PMID- 8272010
TI  - Malignant histiocytosis and large cell anaplastic (Ki-1) lymphoma in childhood:
      guidelines for differential diagnosis--report of the Histiocyte Society.
AB  - A workshop of the Histiocyte Society was recently held, in order to discuss the
      problems and confusion of malignant histiocytosis (MH) and large cell anaplastic
      (Ki-1) lymphoma (LCAL). The aims of this workshop were to clarify the terminology
      for malignant histiocytic disorders and LCAL and to produce reliable criteria for
      diagnosis of both MH and LCAL. This article summarises the conclusions reached.

PMID- 8272009
TI  - Stage III abdominal non-Hodgkin's lymphoma in Costa Rican children: comparison of
      two consecutive trials of treatment.
AB  - Seventy-three patients with Stage III abdominal non-Hodgkin's lymphoma were
      prospectively treated following two sequential protocols (P): L278 P (group A, 33
      patients) (1978-1983) and L384 P (group B, 40 patients), (1984-1991). No patient
      received radiotherapy. The L278 P included 7 drugs: cyclophosphamide, vincristine
      (VCR), adriamycin (ADR), prednisone, methotrexate (MTX), dexamethasone, and 6
      mercaptopurine, given for remission induction, maintenance, and CNS prophylaxis.
      In the L384 P we introduced a consolidation phase consisting of intravenous MTX
      and citrovorum factor rescue, and IV cytosine arabinoside. VCR was also added to
      the monthly doses and the maintenance phase was reduced from 18 to 15 months.
      From January 1988 we changed ADR for epirubicin in the same doses. Prophylactic
      treatment of the CNS, in the L384 P, was intensified by increasing the number of
      doses of MTX IT in the remission, induction, and consolidation phases, and with
      the use of ara-C IT. Laparotomy in 50 patients allowed partial resection in 16,
      and second-look laparotomy was performed in 27 patients. Viable tumor was found
      in four patients. Three patients (G-A) died from metabolic complications and
      another 4 (2 G-A and 2 G-B) failed to attain CR and died. A total of 28 (85%) of
      33 children of G-A and 38 (95%) of 40 children in G-B achieved CR. Five children
      died in remission (2 G-A, 3 G-B). Three patients (G-A) relapsed in the CNS and
      one (G-B) relapsed in the abdomen and died. Disease-free survival at 120 months
      was 70% in G-A and 84% in G-B.

PMID- 8272011
TI  - Pelvic osteosarcoma: problems in management.

PMID- 8272012
TI  - Long-term disease-free survival in a child with refractory metastatic malignant
      germ cell tumor treated by high-dose chemotherapy with autologous bone marrow
      rescues.
AB  - We report the case of a 8-month-old girl who presented with a metastatic
      malignant germ cell tumor (MGCT) that proved to be resistant to chemotherapy,
      including salvage platinum-based combination therapy, surgery, and
      metastatectomy. The child was then treated with high-dose carboplatin, etoposide,
      and cyclophosphamide with autologous bone marrow rescue (ABMR) for two courses,
      since the first course was well tolerated and resulted in serum alpha-f
      etoprotein normalisation. The child remains in complete remission 3 years post
      ABMR and 4 years post-diagnosis, with no detectable treatment-related sequelae.
      Thus, as already reported in adults, dose-intensive chemotherapy with ABMR may
      have curative potential in children with refractory MGCT.

PMID- 8272013
TI  - Toxocariasis simulating hepatic recurrence in a patient with Wilms' tumor.
AB  - We report the case of a 3-year-old girl with stage I Wilms' tumor of favorable
      histology. During the course of chemotherapy 5 months post-diagnosis, an
      abdominal ultrasonogram revealed hypoechoic areas consistent with hepatic tumor
      recurrence. A liver biopsy performed to rule out recurrence of the malignancy was
      suggestive of toxocariasis and the diagnosis was confirmed by serologic testing.
      Although the patient had few classic signs of visceral larva migrans, her
      eosinophilia and family social history should have suggested this possibility.
      This case demonstrates that hepatic toxocariasis should be considered in
      evaluating hepatic hypoechoic lesions in a child, even when features typical of
      the disease are absent.

PMID- 8272014
TI  - Carney's triad: apropos of a new case.
AB  - Carney's triad is defined by the coexistence of at least two of three rare
      disorders, including gastric epithelioid leiomyosarcoma (malignant
      leiomyoblastoma), pulmonary chondroma, and paraganglioma, most often extra
      adrenal and functioning. We report a new case in a 10-year-old girl. The
      paraganglioma, although nonfunctioning, was detected after it was searched for,
      as Carney's triad was suspected. Unrelated seems the development of breast
      fibroadenomas in the same patient. Whenever a patient with one component of the
      triad is encountered, the possibility of this syndrome should be considered and
      the other two components sought.

PMID- 8272015
TI  - [Angiology as a main focus in internal medicine].

PMID- 8272016
TI  - [Transcutaneous oxygen partial pressure and systolic malleolar artery pressure in
      patients with peripheral arterial occlusive disease. Longitudinal measurements
      over 14 days].
AB  - BACKGROUND AND METHODS: In 40 legs of 35 patients with Fontaine's stage I to IV
      peripheral arterial occlusive disease aged between 41 and 77 years, tcPO2 and
      malleolar artery systolic pressure were measured over a period of two weeks.
      RESULTS: It was found that the tcPO2 on the dorsum of the foot varied between
      10.2 and 18.9 mm Hg, in the lower leg between 13.4 and 22.0 mm Hg, and in the
      thigh between 10.8 and 14.5 mm Hg as compared with the baseline value. In
      contrast, the dorsal pedis and anterior tibial arterial blood pressures showed no
      significant variation over time. CONCLUSION: The range of variation of tcPO2 in
      feet, lower legs and thighs must be taken into account in long-term measurements.

PMID- 8272017
TI  - ["Vibration white finger" syndrome in 8 grinders of a large metal manufacturing
      industry].
AB  - PATIENTS: Eight patients with vibration white finger syndrome (VWF) were seen in
      our angiological outpatient department. They were all turbine grinders working in
      the same large factory. One patient presented with a pronounced Raynaud's
      phenomenon only, while all the others additionally complained of numbness,
      weakness and pain affecting both hands. FINDINGS: We requested an intra-arterial
      DSA of the right hand of all patients, which in some patients revealed, in
      addition to severe vasospasm, also blood vessel breaks. The patient who
      apparently was exposed to vibration the longest also had aneurysms affecting the
      capillaries of all fingers.

PMID- 8272018
TI  - [Dose-dependent side effects of acetylsalicylic acid therapy. Results of a
      prospective randomized clinical study in patients with peripheral arterial
      occlusive disease].
AB  - BACKGROUND AND METHODS: In 359 patients with peripheral arterial occlusive
      disease who had undergone percutaneous transluminal angioplasty (PTA), a
      randomized double-blind, controlled clinical study was done to investigate the
      tolerability of acetyl salicylic acid (ASA) given for reocclusion prophylaxis. A
      comparison was made between a conventional daily dose of 900 mg ASA and a dose of
      50 mg ASA. RESULTS: Within an observation period of one year following PTA, 35
      patients (20%) in the 900 mg group, and 32 patients (17%) in the 50 mg group left
      the trial because of side effects (p = NS). Under the higher dose, however,
      severe gastrointestinal side effects (ulcer, haemorrhagic gastritis requiring
      transfusion) were significantly more common (nine patients delta 5.1% vs two
      patients delta 1.1%, respectively; p = 0.03). Overall, 107 patients (30%)
      reported subjective side effects such as upper abdominal pain, a sensation of
      fullness or nausea during the course of the trial. 62 of these patients were from
      the 900 mg group (35%) as compared with 45 patients (24%) in the 50 mg group (p =
      0.02). Self-scoring of epigastric pain on the basis of a visual analogue scale
      revealed a score of 1.3 (95% confidence interval 0.9 to 1.6) in the 900 mg group
      and 0.8 (95% confidence interval 0.6 to 1.0) in the 50 mg group. The subjective
      pain intensity showed a uniform time course for all three types of symptom, with
      a maximum after three months. CONCLUSION: Our results confirm the superior
      tolerability of the lower dose, in particular in elderly patients. For long-term
      treatment, the smallest possible effective dose should be chosen.

PMID- 8272019
TI  - [Prevention of thrombosis: an assessment of current status].

PMID- 8272020
TI  - [Carotid endarterectomy--results of current studies and their consequences].

PMID- 8272021
TI  - [Angiology in the context of internal medicine].

PMID- 8272022
TI  - [The beginning and end of life: cornerstones for ethics in medical research].

PMID- 8272023
TI  - [Friedrich Hoffmann (1660-1742)--a great systematic philosopher of medicine in
      the early 18th century].

PMID- 8272024
TI  - [Atrial myxoma as a cause of multiple peripheral arterial aneurysms].

PMID- 8272025
TI  - Spatial and temporal changes in tissue pH and ATP distribution in a new model of
      reversible focal forebrain ischemia in the rat.
AB  - The effects of reversible middle cerebral artery occlusion on regional pH and ATP
      distribution were studied in a new stroke model in rats by a planimetric method.
      Thirty minutes of ischemia was followed by 2, 4 and 24 hours of reperfusion.
      Ischemia resulted in acidosis and ATP depletion. In some areas tissue pH reached
      the threshold of the umbelliferone method (about pH 6.0). Areas with ATP
      depletion were significantly smaller than regions of pH alteration not only at
      the end of ischemia but during the first 4 hours of recirculation as well. By 4
      hours of reperfusion large areas with altered pH were associated with ATP
      depletion in smaller regions, mostly in the hippocampus and the frontal cortex.
      The areas of ATP depletion were acidic initially, but by 4 hours alkaline pH
      could also be detected. Twenty four hours after ischemia alkaline areas (pH >
      7.4) were found with ATP depletion, suggesting irreversible tissue damage, in
      cortical areas, in the hippocampus, and in the thalamus. By 24 hours of
      reperfusion there was no significant difference between the size of areas with
      altered pH and ATP depletion.

PMID- 8272026
TI  - Brain regional distributions of monoamine oxidase activities in postnatal
      development in normal and chronically manganese-treated rats.
AB  - To investigate the hypothesis that manganese toxicity may affect the development
      of the monoamine oxidases (MAOs) in brain, the regional distributions of the A
      (serotonin-oxidizing) and B (benzylamine-oxidizing) forms of MAO were determined
      in manganese-treated (1 mg or 10 mg of MnCl2.4H2O per ml of drinking water from
      conception onwards until the rats were used for experiments) and untreated male
      rats during various stages of postnatal development. The age-related variations
      in regional MAO-A activities (especially in pons and medulla and in cerebellum)
      were more marked than those in regional MAO-B activities. The MAO-A:MAO-B
      activity ratios decreased in all regions during development. Chronic manganese
      treatment (at the specified doses) did not significantly alter the age-related
      changes in regional MAO-A and MAO-B activities; nor were the A:B activity ratios
      affected. The results suggest that there is differential expression of MAO
      isoforms in various brain regions during postnatal development but the expression
      is not affected by chronic manganese toxicity.

PMID- 8272029
TI  - Differential diagnosis of seizures.
AB  - Distinguishing epileptic events from nonepileptic paroxysmal neurologic events
      represents a common diagnostic challenge. Syncope, either cardiac or noncardiac,
      can appear similar to atonic and even convulsive seizures. Breath holding and
      benign paroxysmal vertigo in children may be confused with epilepsy. Classic
      migraine, transient global amnesia, and transient ischemic attacks may resemble
      epileptic seizures. Sleep disorders, including nocturnal movements, parasomnias,
      and narcolepsy also may resemble epileptic seizures. Most movement disorders are
      distinguished easily from epilepsy; however, paroxysmal dyskinesias may resemble
      atonic or reflex seizures. The correct diagnosis can be established and
      appropriate treatment can be instituted by relying on routine and prolonged EEG,
      EKG, and sleep studies, when appropriate.

PMID- 8272028
TI  - Long-term observations in gerbil brain following transient cerebral ischemia:
      autoradiographic and histological study.
AB  - We investigated the long-term changes that occur in the gerbil brain following
      transient cerebral ischemia using histology and receptor autoradiography.
      Transient ischemia was induced for 3 and 10 min, and animals were allowed to
      survive for 8 months. A histological study showed that 3-min ischemia caused
      neuronal damage and mild atrophy only in the hippocampal CA1 sector, and that 10
      min ischemia produced severe neuronal damage and marked shrinkage in the
      hippocampal CA1 and CA3 sectors. Furthermore, severe neuronal damage was seen in
      the striatum after 10-min ischemia. Autoradiography study revealed that 3-min
      ischemia caused a significant reduction in [3H] naloxone binding in the frontal
      cortex, striatum, dentate gyrus, and thalamus, whereas [3H]SCH 23390 and [3H]
      forskolin binding was not significantly altered in all regions. In contrast, 10
      min ischemia produced marked alteration in these binding sites in the striatum,
      hippocampus, thalamus, and substantia nigra. The alteration was especially
      notable in the hippocampal region and substantia nigra. These results indicate
      that hippocampal damage after transient ischemia, compared with that in other
      regions, is not static, but particularly progressive. Furthermore, they
      demonstrate a reduction in adenylate cyclase system in the striatum and
      substantia nigra after transient ischemia. Moreover, our results suggest that
      long-term survival after ischemia may induce synaptic modification of
      neurotransmitter and adenylate cyclase system in the hippocampus.

PMID- 8272030
TI  - Seizures and epilepsy in infancy and childhood.
AB  - The evaluation, diagnosis, and treatment of childhood epilepsy or isolated
      seizures deserve special consideration. Whenever possible, a working diagnosis of
      an epilepsy syndrome should be implemented early in the course of evaluation to
      help plan the necessary investigations and acute and chronic treatment. The plan
      will evolve over a number of years as the patient's syndrome is better defined.
      The overall neurologic status of the child and response to therapy are important
      prognostic factors. Treatment proceeds after balancing antiepileptic drug
      efficacy versus adverse drug effects. The length of treatment, discussion of
      prognosis, and likelihood for genetic transmission are all related to the proper
      diagnosis of epilepsy syndromes.

PMID- 8272027
TI  - Endogenous ornithine in search for CNS functions and therapeutic applications.
AB  - The vertebrate brain has the machinery to transport arginine and ornithine, and
      to form within nerve endings from these amino acids glutamate and GABA, the major
      excitatory and inhibitory neurotransmitters. Ornithine aminotransferase is a key
      enzyme of the Arg-->Orn-->Glu-->GABA pathway; the physiological significance of
      this pathway is still unclear. With 5-fluoromethylornithine, a selective
      inactivator of ornithine aminotransferase, a tool is in our hands that allows us
      to study biochemical and behavioral consequences of elevated tissue ornithine
      concentrations. Increase of the rate of hepatic urea formation, and of ornithine
      decarboxylation are the most important changes in vertebrates following
      inactivation of ornithine aminotransferase. Administration of 5
      fluoromethylornithine prevented the accumulation of lethal concentrations of
      ammonia in brain, and ameliorated pathological consequences of thioacetamide
      intoxication. Inhibition of ornithine catabolism has, therefore, potentials in
      the therapy of those hyperammonemic states which are characterized by a
      conditional deficiency of ornithine. The enhancement of polyamine formation due
      to elevated ornithine concentrations may allow us to favorably affect tissue
      regeneration following injury.

PMID- 8272031
TI  - Epilepsy and pregnancy. New issues for an old disorder.
AB  - Clinicians and their women patients with epilepsy face difficult decisions. There
      is evidence to suggest that antiepileptic drugs increase the risk of major
      malformations, minor anomalies, neonatal hemorrhage, and delayed fetal growth and
      development. Maternal seizures also appear to be disadvantageous to the fetus,
      increasing the risk of miscarriage, premature labor, intracranial hemorrhage, and
      perhaps, developmental or learning difficulties. Both medications and seizures
      have the potential to cause difficulties. This article discusses change in
      antiepileptic drug metabolism, changes in seizure frequency, adverse pregnancy
      outcomes, and principles of management.

PMID- 8272032
TI  - Seizures and epilepsy in the elderly.
AB  - Recent data indicate that the incidence and prevalence of seizures and epilepsy
      rise substantially in the elderly. Little well-founded information is available
      on which to base treatment decisions. This article discusses cause, diagnostic
      evaluation, and antiepileptic drug pharmacology. Tentative treatment suggestions
      are offered, emphasizing the limits of available knowledge.

PMID- 8272033
TI  - Partial seizures of frontal and temporal origin.
AB  - The majority of medically refractory partial epilepsies arise in the frontal and
      temporal lobes and represent a major challenge to the neurologist. The
      phenomenology of seizures from these regions is diverse and fascinating, at times
      lying on the border of many medical specialties. An appreciation of the wealth of
      potential phenomena can lead to more accurate diagnosis and treatment.

PMID- 8272034
TI  - Post-traumatic seizures.
AB  - Acute traumatic brain injury causes a cascade of changes in brain metabolism,
      blood flow, and homeostasis that are challenges to survival. Seizures, whether
      focal or convulsive, may be a manifestation of the acute injury response and are
      liable to complicate management. This article discusses mechanisms and
      biochemical effects of brain injury, cellular mechanisms of epileptogenesis,
      genetic factors, prevention and prophylaxis, alteration of brain injury
      responses, and recommendations for management.

PMID- 8272035
TI  - Status epilepticus.
AB  - Status epilepticus is defined as having two tonic-clonic convulsive seizures in a
      row without regaining consciousness or continuous absence, complex partial, or
      partial seizure activity for 30 minutes or longer. This article discusses
      classification and prognosis of status epilepticus, principles of management, and
      drug treatment in adults and adolescents.

PMID- 8272036
TI  - Pitfalls of EEG interpretation in epilepsy.
AB  - Electroencephalogram remains the single most valuable investigation in patients
      with known or suspected seizure disorders. Errors made in the interpretation of
      electroencephalogram studies are common and have significant consequences for the
      patient. This article presents a logical approach to the analysis of
      electroencephalograms, illustrating the principle pitfalls in each step of this
      analysis.

PMID- 8272037
TI  - Neuroimaging in epilepsy: recent developments in MR imaging, positron-emission
      tomography, and single-photon emission tomography.
AB  - PET, SPECT, and MR imaging are valuable techniques in the diagnosis and treatment
      of the epilepsies. MR imaging displays structural disturbances such as neoplasms;
      dysplasias, and atrophy with great sensitivity. Recent advances in MR technology
      also will permit the imaging of cerebral blood flow. PET and SPECT show
      physiologic derangements in epilepsy, including localized reductions in cerebral
      blood flow and metabolism and highly focal decreases in neurotransmitter receptor
      binding. These methods are particularly valuable when combined with
      electroencephalogram evaluation in selecting patients for epilepsy surgery. MR
      imaging is also a valuable diagnostic tool in the routine care of epilepsy
      patients.

PMID- 8272038
TI  - Antiepileptic medication interactions.
AB  - This overview of AEM interactions underscores the importance of understanding the
      pharmacokinetic properties of AEMs and demonstrates the need for careful analysis
      of AEM concentrations in situations in which combinations of AEMs are used.
      Although generalizations concerning the clinical significance of drug
      interactions can be made, major interpatient variations occur. Thus, whenever an
      AEM is added or deleted, concentrations of drugs should be measured. Refractory
      individuals or those with multiple seizure types may need polypharmacy, and,
      under these circumstances, both total and unbound concentrations may need to be
      measured. New AEMs may have the potential for clinically significant
      interactions. If these are not identified and understood early, the development
      and ultimate clinical usefulness of these new agents may be inhibited.

PMID- 8272039
TI  - New antiepileptic medications.
AB  - Several new compounds are undergoing extensive investigation in the United States
      and Europe. The available animal and human studies suggest that these new
      antiepileptic drugs are very promising. Some or all of them will be approved for
      clinical use during the next decade. New antiepileptic drugs offer new options in
      the treatment of epilepsy. Although there already has been considerable testing
      of these drugs, additional studies that incorporate traditional medical outcome
      measures and quality of life measures remain to be done to establish the ultimate
      role of the new antiepileptic drugs in the treatment hierarchy for epilepsy.

PMID- 8272040
TI  - Epilepsy surgery.
AB  - Epilepsy surgery is assuming greater importance in treating patients with partial
      epilepsy whose seizures are uncontrolled with antiepileptic drugs. Many good
      candidates for surgical treatment are not presented with the option of surgery.
      The evaluation for epilepsy surgery is extensive and includes several stages of
      noninvasive and invasive testing. As more sophisticated noninvasive tests
      develop, fewer patients require invasive monitoring studies such as depth or
      subdural electrodes. The principal forms of surgical treatment include focal
      resection, corpus callosotomy, and hemispherectomy. Temporal lobectomy remains
      the most common and effective form of epilepsy surgery. Frontiers of epilepsy
      surgery include resective surgery for intractable infantile spasms and multiple
      subpial transections for patients whose seizure foci are in sensory, motor, or
      languages cortex. Additional studies are needed to define the safety and efficacy
      of these new procedures.

PMID- 8272041
TI  - Vaccination coverage of 2-year-old children--United States, 1991-1992.
AB  - Protecting children against vaccine-preventable diseases is a national priority
      in public health. Because approximately 80% of childhood vaccine doses are
      recommended for administration during the first 2 years of life, vaccination
      coverage among children must be continuously monitored. National estimates of
      vaccination coverage were calculated annually from 1959 through 1985 but not for
      1986-1990. Beginning in 1991, national estimates of vaccination coverage of
      preschool children have been available through the National Health Interview
      Survey (NHIS), a national survey of the civilian noninstitutionalized population
      conducted by CDC's National Center for Health Statistics. This report presents
      1992 national estimates of vaccination coverage for 2-year-old children and
      describes changes from 1991 to 1992.

PMID- 8272042
TI  - HIV prevention practices of primary-care physicians--United States, 1992.
AB  - Primary-care physicians can be important providers human immunodeficiency virus
      (HIV)-prevention services to their patients. In 1991, 15% of U.S. adults reported
      having been tested for HIV antibody; of these, 55% reported their most recent HIV
      test had been in a physician's office or a hospital. During 1992, CDC and the
      Health Resources and Services Administration (HRSA) commissioned a national
      survey to characterize the types of HIV prevention services provided by primary
      care physicians and barriers to the provision of these services. This report
      summarizes the results of the survey.

PMID- 8272043
TI  - Occupational pesticide poisoning in apple orchards--Washington, 1993.
AB  - During July-December 1993, the Washington Department of Health (WDOH) received
      and conducted follow-up investigations of 26 reports of occupational illness
      related to exposure to mevinphos (Phosdrin), an organophosphate (OP) insecticide.
      The reports involved illnesses during June 13-August 18, 1993, in persons working
      in 19 different apple orchards; all involved use of mevinphos to control apple
      aphids. This report summarizes the results of these investigations by WDOH.

PMID- 8272044
TI  - Update: influenza activity--United States, 1993-94 season.
AB  - From mid-November through December 1993, influenza activity in the United States
      increased. This report summarizes surveillance information regarding influenza
      activity in the United States from October 3, 1993, through January 1, 1994.

PMID- 8272045
TI  - Public health core functions--Alabama, Maryland, Mississippi, New Jersey, South
      Carolina, and Wisconsin, 1993.
AB  - The three core functions of public health are assessment, policy development, and
      assurance. Within these core functions, CDC has identified 10 basic public health
      practices that are integral to the operation of state and local health agencies
      (Table 1). As a part of assessing the core functions of public health, public
      health officials at local health departments in six states (Alabama, Maryland,
      Mississippi, New Jersey, South Carolina, and Wisconsin) were surveyed in 1993 by
      the state local liaison affiliates of the Association of State and Territorial
      Local Health Liaison Officials, the School of Public Health at the University of
      North Carolina at Chapel Hill, and CDC. This report summarizes the findings from
      this survey.

PMID- 8272046
TI  - Adult blood lead epidemiology and surveillance--United States, third quarter,
      1993.

PMID- 8272047
TI  - Performance evaluation program for Mycobacterium tuberculosis drug-susceptibility
      testing process.

PMID- 8272048
TI  - Prevalence and characteristics of alcohol consumption and fetal alcohol syndrome
      awareness--Alaska, 1991 and 1993.
AB  - Fetal alcohol syndrome (FAS) is a leading preventable cause of birth defects and
      mental retardation in the United States (1). To reduce alcohol exposure to the
      developing fetus and to modify health-related behaviors, public health
      professionals and policy makers require effective methodologies to identify at
      risk populations and develop strategies for preventing this problem. In Alaska,
      the prevalence of FAS is higher than the national average (2). Because of the
      need for information to assist in planning prevention programs, identifying
      training needs for service providers, and monitoring changes in factors related
      to FAS in target populations, the Alaska Department of Health and Social Services
      (ADHSS), the Indian Health Service (IHS), and CDC have conducted surveys to
      measure relevant knowledge, attitudes, beliefs, and behaviors (KABBs) in selected
      populations in Alaska. This report summarizes survey findings during 1991 and
      1993 regarding the prevalence of alcohol consumption by and characteristics of
      women of childbearing age in Alaska and FAS-related KABBs in Alaska residents.

PMID- 8272049
TI  - National immunization days and status of poliomyelitis eradication--Philippines,
      1993.
AB  - The Western Pacific Regional Committee of the World Health Organization (WHO)
      resolved in 1988 to eradicate poliomyelitis in the region by 1995. Despite
      intensified surveillance for acute flaccid paralysis (AFP), reported cases of
      poliomyelitis decreased from 5485 in 1989 to 1909 in 1992. Of the five countries
      in the region that continue to report endemic poliomyelitis (Cambodia, People's
      Republic of China Laos, Republic of the Philippines, and Vietnam), reported
      incidence is lowest in Philippines, which also was the first country in the
      region to undertake national immunization days (NIDs) with oral poliovirus
      vaccine (OPV); in addition, other vaccines were administered at vaccination posts
      by trained health workers. This report assesses the impact of Philippines' first
      NID, which was initiated as part of its poliomyelitis eradication efforts, and
      summarizes progress toward eradication of poliomyelitis in Philippines.

PMID- 8272050
TI  - [Prophylactic effects of mitomycin C (MMC) on the liver recurrence in a rabbit
      gastric VX2 cancer model with high frequency of the recurrence].
AB  - Prophylactic effects of mitomycin C (MMC) injection protocol with different dose,
      periods and routes on liver recurrence were examined, using 53 gastric VX2 cancer
      rabbits. All the gastric cancer lesions without liver metastases were resected 14
      days after implantation of VX2 cancer cells into the stomach, and all the animals
      were autopsied 14 days after resection. Multiple liver recurrence was found in
      75% of MMC non-injection control 8 rabbits. The recurrence was not found in 10
      animals with portal MMC 0.5 and 0.25mg/kg injection after resection, although 80%
      of 5 animals with the 0.125mg/kg injection after resection revealed the
      recurrence. The recurrence was not found in 4 animals with peripheral MMC
      1.0mg/kg injection, but found in 60% of 5 animals with the MMC 0.5mg/kg injection
      after resection. In the animals with peripheral MMC 0.25mg/kg injection 2, 1 and
      0 days before resection and with portal MMC 0.125mg/mg injection after resection,
      the recurrence was found in 83, 60 and 80% of 6, 5 and 5 respective animals.
      These results suggest that prophylactic injection of MMC for liver recurrence is
      more effective in portal than peripheral injection, but that the preoperative and
      peripheral injection has no efficacy.

PMID- 8272051
TI  - [Intrahepatic cholangiocarcinoma: proposal of new macroscopic classification].
AB  - From the analysis of 19 resected intrahepatic cholangiocarcinoma (ICC) from 1980
      to 1991 in the National Cancer Center Hospital, we classified them into three
      subcategories, mass-forming ICC, infiltrating ICC and papillary ICC, according to
      the morphologic pattern. Mass-forming ICC, which made an apparent mass lesion in
      the liver, showed a spread based on the intrahepatic metastasis with a frequent
      remnant hepatic recurrence. Infiltrating ICC caused a stricture or an obstruction
      of intrahepatic bile duct with a spread along the Glisson's capsule without
      forming a mass in the liver and yielded no remnant liver recurrence except for a
      local recurrence in the patient with positive surgical margin. Intraductal
      papillary ICC, which appeared a special type of ICC, developed a papillary
      projection into the ductal lumen. Three patients of mass-forming ICC and one of
      papillary ICC survived more than 5 years. The different biologic behaviour should
      be considered when formulating an operative procedure for each type of ICC.

PMID- 8272052
TI  - [Long-term follow-up results of stage III and IV thymomas and thymic carcinomas
      invading the great veins].
AB  - A series of 24 patients with stage III and IV thymomas and thymic carcinomas were
      reviewed with respect to the invasiveness of the superior vena cava (SVC) and
      brachiocephalic veins (BCV). Masaoka staging revealed stage III disease in 14
      patients and stage IV in 10. Follow-up ranged from 3 months to 12 years and 10
      months. In 9 patients with stage III disease involving the great veins, 6
      patients underwent total resection, 2 subtotal resection, and one exploratory
      thoracotomy. Reconstruction of SVC was done in 2 patients and of left BCV in 7
      and angioplasty of SVC in one. Although there were 4 tumor deaths and one
      myasthenic death, 4 patients were alive and tumor free. The longest survival
      after total resection with SVC replacement was 11 years and 7 months. In 3
      patients with stage IV disease invading the great veins, 2 patients underwent
      partial resection and one received radiotherapy alone. Although 2 patients died
      of generalized metastases and respiratory failure respectively, one remained
      alive 2 years and 2 months with carcinoma. Although long-term survivors were
      obtained in the patients with adventitial involvement, prognosis was poor in the
      patients with intimal invasion.

PMID- 8272053
TI  - [Prognostic value of Ia-antigen, fibronectin, laminin and type IV collagen in
      pulmonary squamous cell carcinoma].
AB  - Presence of absence of four immunohistological markers were investigated in fifty
      four cases of pulmonary squamous cell carcinoma. Ia-antigen (HLA-DR), fibronectin
      (Fn), laminin (La), and type IV collagen were present in 9 cases (16.7%), 13
      (24.0), 24 (44.4) and 12 (22.2) respectively. Three markers were present in 6
      cases, two 13, one in 14 and none in 21. Higher positive rate of Fn among N (-)
      group in TNM classification was statistically significant when compared with that
      of N (+) group. In 13 of 14 cancer death cases, less than one markers were
      present, while all the cases in which more than two markers were present were
      alive during the follow up periods. The author concludes that Fn by itself is a
      useful prognostic indicator and when combined with other three markers, it can
      predict accurate prognosis.

PMID- 8272054
TI  - [An operative case of empyema necessitatis].
AB  - A case of empyema necessitatis presenting a mass in the retroperitoneal space is
      reported. Computer tomography preoperatively revealed the transdiaphragmatic
      abscess with calcified capsule. The operation was performed by means of resection
      of the abscess together with overlying ribs. Dead space after resection of the
      lesion was filled up with intercostal muscles. Empyema necessitatis is rare after
      introduction of antituberculous drugs. However, recognition of this disease is
      necessary for an appropriate surgical management. Total resection of the abscess
      followed by filling of the dead space with the intercostal muscles should be
      considered as a useful alternative method.

PMID- 8272055
TI  - [Postoperative adjuvant high-dose rate interstitial radiotherapy for thoracic
      esophageal cancer: usefulness of a latissimus dorsi muscle flap: preliminary
      report].

PMID- 8272056
TI  - [Effects of tumor removal and body weight loss on insulin resistance: preliminary
      report].

PMID- 8272057
TI  - [Quantitative analysis of TNFmRNA in peripheral mononuclear cells and its
      clinical application: preliminary report].

PMID- 8272058
TI  - [Changes of plasma atrial natriuretic peptide (ANP) in patients undergoing
      pulmonary resection].

PMID- 8272059
TI  - [A possible occurrence of right to left shunt flow through foramen ovale during
      laparoscopic cholecystectomy: preliminary report].

PMID- 8272060
TI  - [Matrix metalloproteinase 9 (92kDa gelatinase/type IV collagenase) is implicated
      in liver metastasis in colorectal cancers: preliminary report].

PMID- 8272061
TI  - [Immunohistochemical and histopathological study of expression of epidermal
      growth factor receptors in gastric cancer].
AB  - To evaluate the importance of epidermal growth factor receptors (EGFR) in the
      growth and progression of human gastric cancer, we immunohistochemically stained
      EGFR in specimens of gastric cancer and compared the results with
      histopathological findings. Fresh frozen sections obtained from 65 cases of
      gastric cancer were stained by indirect immunostaining technique using Oncogene
      Scince Inc. Cat. No. GR01 (528 IgG reported by Kawamoto et al.) as anti-EGFR
      monoclonal antibody. Of the 65 cases of gastric cancer, 17 (26.2%) were EGFR
      positive. In differentiated cancer, EGFR was positive in 15 of 28 cases (53.6%)
      of advanced cancer, and 1 of 14 (7.1%) of early stage cancer. In undifferentiated
      cancer, 1 of 15 cases (6.7%) of advanced cancer was positive, but all 8 cases of
      early stage cancer were negative. In differentiated cancer, EGFR was more
      frequently positive in cases of advanced cancer than in those of early stage
      cancer (p < 0.05). These results suggest that EGFR are expressed or increase in
      the transition process from early to advanced stage cancer in differentiated
      gastric cancer. In addition, the lower EGFR-positive rate in cases of
      undifferentiated cancer than in those of differentiated cancer suggests that an
      increase in EGFR is not needed for cancer growth in most cases of
      undifferentiated cancer.

PMID- 8272062
TI  - [Limited surgery for early gastric cancer].
AB  - The prognosis of the resected "early gastric cancer" is very good, especially in
      mucosal cancer. In Japan, the surgery for the gastric cancer generally is
      subtotal gastrectomy combined with R2-lymph nodal dissection. But, some cases are
      free of lymph nodal metastasis, and might be cured without its dissection. We
      analyzed resected specimens of early gastric cancer pathologically, and assessed
      what cancers we could do the limited operation without impairing curability.
      Lymph nodal metastasis of the mucosal cancer developed 2.1% of all 291 mucosal
      cancers, and of the submucosal cancer, 15.7% of 229 cases. Lymph vessel
      permeation depicted 5.2% and 82.1%, respectively. As for the mucosal cancer, less
      than 10 mm in maximum diameter, there were no lymph vessel permeations nor lymph
      nodal metastasis. In these cases, the limited operation, especially the local
      resection and the endoscopic resection could be available without any fear of
      cancer residue. In contrast, the submucosal cancer was not considered the
      candidate of the limited surgery.

PMID- 8272063
TI  - [Evaluation regarding effect and quality of life after distal pancreatectomy
      combining total gastrectomy].
AB  - Distal pancreatectomy combined with total gastrectomy for gastric carcinoma was
      evaluated in regard to the availability and quality of life for patients. We
      performed a question-naire survey of their daily life, especially regarding
      postpancreatectomy diabetes, for 67 patients passed 5 years after total
      gastrectomy inclusive of five cases without pancreatectomy as control. Eleven
      cases developed diabetes mellitus which needed insulin injection after distal
      pancreatectomy excluding three patients with glucose intolerance before
      operation. These were 19% of cases performed pancreatectomy, while there was no
      diabetes in cases without pancreatectomy. The incidence of postpancreatectomy
      diabetes was 60 per cent of the cases which underwent Appleby operation (65%
      pancreas resection), while it was 50 percent of the cases which underwent total
      gastrectomy combined with distal pancreatectomy (50% resection). There is
      significant difference at < 0.05 level. The incidence of postpancreatectomy
      diabetes was increased as passing of years after operation. These results suggest
      that distal pancreatectomy combining total gastrectomy improves the prognosis of
      patients with nodal metastasis. But considering the occurrence of
      postpancreatectomy diabetes, it should be emphasized the adequate indication is
      needed for the operation, and close and long-term follow up is essential for
      keeping QOL.

PMID- 8272064
TI  - [Endotoxin-inactivating activity in normal and D-galactosamine induced liver
      failure rats].
AB  - Hepatic failure model rats were prepared by administration of D-Galactosamine
      (Gal) to clarify the endotoxemia under the hepatic failure. Endotoxin was
      injected from the femoral vein and the endotoxin level in blood was measured
      periodically in normal and Gal induced liver failure rats. Further endotoxin was
      added to plasma, incubated and periodically the endotoxin level in plasma was
      measured. After the injection of endotoxin, liver biopsy was made and by
      immunohistochemical staining with Factor C, the localization of endotoxin in the
      liver was studied. The endotoxin level in blood before the injection was within
      the normal range in both groups. In the in vivo test, the endotoxin level of the
      Gal group was significantly higher and its disappearance rate was also
      significantly lower than the control after the injection of endotoxin. In the in
      vitro test, the endotoxin level of the Gal group was significantly higher. After
      one hour, endotoxin was stained on Kupffer cells and hepatocytes in the control
      group only. In the Gal group, no intrinsic endotoxemia was noted, but it was
      presumed that endotoxemia is easily caused due to the lowered inactivation of
      endotoxin in plasma and in the liver.

PMID- 8272065
TI  - [The role of Ca(2+)-ATPase and oxygen radical in reperfusion injury of rat
      liver].
AB  - The effects of ischemia and reperfusion with and without oxygen radical
      scavengers and xanthine oxidase inhibitors on Ca(2+)-ATPase activity were
      examined in the rat liver of 5 min ischemia followed by 5 and 10 min reperfusion.
      Ischemia was produced by the ligation of right hepatic artery and right portal
      vein. Superoxide dismutase, catalase and allopurinol were administered by
      subcutaneous injection of 60,000U/kg, 90,000U/kg and 200mg/kg, respectively
      before ligation. Reaction products of Ca(2+)-ATPase were morphometrically
      analyzed by RUZEX IIIU. Histochemically, Ca(2+)-ATPase activities were
      demonstrated on plasma membrane of liver cells, bile canaliculi and Kupffer cells
      involving mitochondria in liver cells of control rats. Ca(2+)-ATPase activities
      were depressed in the central lobes of liver after 5 min ischemia followed by 5
      and 10min reperfusion. However, the activities of Ca(2+)-ATPase were not
      depressed by addition of oxygen radical scavengers and xanthine oxidase inhibitor
      before ischemia. These results suggest that oxygen free radicals may influence
      Ca(2+)-ATPase activity and contribute to liver cell damage due to ischemia
      reperfusion.

PMID- 8272066
TI  - [Warm ischemia and reperfusion injury in the regenerating rat liver].
AB  - The effect of warm ischemia and reperfusion injury in the regenerating rat liver
      after portal vein branch ligation (PBL) was examined by monitoring hepatic high
      energy phosphorous metabolism using in vivo Phosphorus-31 Magnetic Resonance
      Spectroscopy (31P-MRS). On 14 days after 70% occlusion of the portal vein, energy
      metabolism of non-occluded lobe of the liver was evaluated by measuring the ratio
      of beta-ATP to Pi obtained using 31P-MRS. During 30min-ischemia, beta-ATP/Pi
      dropped down similarly below the limit of observation in both of control and
      regenerating liver. However, after reperfusion, in the regenerating liver, the
      earlier and better recovery of beta-ATP/Pi was observed compared with the
      control. In the any examination of m-GOT, GPT, increase in enzyme level was
      apparently restrained in the PBL group. On the pathological examination,
      centrilobular necrosis and hepatocyte degeneration were remarkable in the normal
      liver, while in the regenerating liver, these changes were slight. In conclusion,
      these results suggest that reperfusion injury observed in the regenerating liver
      seems to be reduced compared with that in the normal liver. Functional and
      structural changes in the regenerating liver could be claimed as a course of this
      observation. However, to understand the mechanism, further study will be needed
      both in morphological and biochemical aspect.

PMID- 8272067
TI  - [Hepatocellular transplantation for metabolic support in experimental acute liver
      failure in rats].
AB  - The function of intrasplenic transplanted hepatocytes in acute liver failure was
      studied in an experimental model using rat (Lewis syngeneic rat). Acute ischemic
      liver failure was induced by occlusion of the proximal portal vein and hepatic
      artery immediately following extracorporeal porto-femoral venous bypass. Rats in
      group I were untreated and served as control (n = 6). Rats in group II received
      an intrasplenic transplant of hepatocytes (4 x 10(7) cells) 2 days before liver
      ischemia (n = 6). Rats in group III received an intrasplenic injection of the
      equal quantitative liver homogenate instead of hepatocytes 2 days before liver
      ischemia (n = 6). Serum ammonia and blood glucose were measured before, 1 hour
      and 2 hour after ischemia. The survival times of animals were evaluated. Serum
      ammonia was remarkably increased after ischemia in group I (1 hr = 937, 2 hr =
      1220 micrograms/dl). On the other hand, in group II, the elevation of serum
      ammonia was significantly suppressed, less than half of that in group I (1 hr =
      425, 2 hr = 463 micrograms/dl). That in group III was similar to group I. Blood
      glucose was remarkably decreased in all groups, but it was statistically higher
      in group II (1 hr = 48, 2 hr = 28 mg/dl) than in others (group I 1 hr = 23, 2 hr
      = 2, group III 1 hr = 29, 2 hr = 10 mg/dl). The mean survival time in group II
      (191 minutes) was two times longer than those in another two groups.

PMID- 8272068
TI  - [Study on the complete parathyroidectomy and parathyroid autoimplantation for
      secondary parathyroidism in chronic renal failure].
AB  - We studied on the operative indication and therapeutic effect of complete
      parathyroidectomy and autoimplantation for chronic hemodialysis. Twenty three
      surgical resections were performed on 21 patients who had been received long-term
      hemodialysis. Total resected glands from these patients were 83 and the mean
      total parathyroid's weight was 3.2 gram. The detection rate of
      hyperparathyroidism was 50.0% by scintigram, and 72.9% by computed tomography
      (CT). The mean diameter of resected glands proved to be 5 to 6mm larger than that
      estimated by CT. There was no statistical correlation between the durations of
      hemodialysis and the total parathyroid's weights. Our study revealed that the
      mean weight of 5 cases without 1,25(OH)2D3-plus therapy was 5.8 gram, which was
      significantly heavier than that with this therapy. Histopathologically, the
      larger glands often showed nodular growth, but the smaller glands tended to show
      diffuse hyperplasia. There was a positive correlation (r = 0.93, p < 0.01)
      between the weights of the resected glands and serum CPTH values only in those
      cases with the glands weighing equal or less than 4 gram.

PMID- 8272069
TI  - [Lipid peroxide and free radical scavengers in congenital heart disease with
      pulmonary hypertension].
AB  - There is a strong possibility that lipid peroxide (LPO) exerts a great influence
      on the persistence of pulmonary vascular obstruction (PVO) after radical
      operation of congenital heart disease with pulmonary hypertension (PH). We
      investigated the relationship between LOP and PVO, and discussed the effects of
      scavengers. Fourteen cases of infantile open heart surgery were investigated.
      LPO, superoxide dismutase SOD and reduced glutathione (GSH) were measured in
      blood and lung tissue. In the cases of PH group, the levels of lung tissue and
      plasma LPO showed significantly higher than those of PS group (p < 0.05) before
      and after radical operation. The levels of Pp/Ps and pulmonary vascular
      resistance (PVR) of PH cases showed still higher than those of PS group (p <
      0.05) even after radical operation. In addition, the levels of plasma and lung
      tissue SOD, lung tissue GSH of PH cases were lower than those of PG group. These
      suggest that LPO plays an important role as the cause of PVO before operation and
      which remains unchanged even after operation. It is to be expected that increase
      of the free radical scavengers will be effective to suppress the generation of
      LPO and at last to reduce the level of PVR after operation.

PMID- 8272070
TI  - [A case report of CMV hepatitis and nephropathy after living related renal
      transplantation].
AB  - Cytomegalovirus (CMV) infection is serious complication after clinical renal
      transplantation. A case of CMV hepatitis and nephropathy after living related
      renal transplantation was reported. A 32-year-old women with chronic renal
      failure due to systemic lupus erythematosis received a renal transplant from her
      mother. On day 35 after operation, she developed high fever with hepatic and
      renal damage and was diagnosed as CMV infection from clinical course and
      virological examination. Although the use of anti-CMV high titer gamma globulin
      with reduction of immunosuppressant therapy could not cure the infection, the
      administration of Ganciclovir improved hepatic and renal damage without
      deterioration of renal graft function.

PMID- 8272071
TI  - [A case complicated with a large perforation at the great curvature of the
      stomach after 6 days of omentopexy for tuberculous empyema].
AB  - A 72-year-old male with tuberculous empyema underwent omentopexy following
      thoracic window. However, acute abdomen developed 6 days after the latter
      surgery. During emergency laparotomy; a large perforation (8.5 x 3cm) was found
      at the great curvature of the stomach. Histology of the resected specimen showed
      this was ischemic ulcer, which was thought to have been caused by circulatory
      failure at the areas supplied by the right gastroepiploic arteries after pedicled
      omental flap. This case suggested that much attention should be paid not only to
      the blood circulation of the graft but also to that of the stomach.

PMID- 8272072
TI  - [Blunt trauma with combined femoral arterial and venous occlusion].
AB  - Blunt trauma to common femoral artery is rare, and it is frequently unrecognized.
      A 61-year-old man who fell while carrying a log and struck on his right groin,
      presented right leg edema and intermittent claudication one month later. Both
      right femoral arterial and venous occlusion was suspected by Doppler flowmeter,
      confirmed by venography and arteriography which showed concomitant external iliac
      arterial occlusion. He underwent prosthetic bypass grafting from common iliac
      artery to common femoral artery and embolectomy of femoral vein. Circulation to
      the right leg was restored, but postphlebitic syndrome had remained which was
      ameliorated by wearing the elastic stocking.

PMID- 8272073
TI  - [In vitro studies with a cation exchange resin mixture for direct hemoperfusion
      in the treatment of hyperkalemia: preliminary report].

PMID- 8272074
TI  - [Increased activity of choline kinase in human breast cancer and 7, 12
      dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma, and activated by
      17 beta-estradiol: preliminary report].

PMID- 8272075
TI  - [The production of spontaneous lung metastasis model from transplanted colon
      carcinoma in nude rat: preliminary report].

PMID- 8272076
TI  - Release of DR molecules from complexes with invariant chain through the formation
      of a C-terminal 25 kDa invariant chain fragment.
AB  - To investigate how class II major histocompatibility complex (MHC) molecules are
      released from complexes with invariant chain (Ii), we studied a 25 kDa Ii
      fragment (p25) detected by Western blotting in affinity chromatographed DR
      preparations. The p25 species corresponds to the non-transmembrane, C-terminal Ii
      fragment 107-232. It was determined by gel filtration chromatography that the p25
      fragment has a relative molecular mass (M(r)) of 46 kDa, indicating that this Ii
      fragment is present as dimers in B cell lysate. Two independent approaches were
      followed to demonstrate that generation of the p25 fragment takes place shortly
      before, or concomitantly to, loading of class II MHC molecules with antigen
      fragments. First, it was shown that a fraction of the p25 molecules is resistant
      to endoglycosidase H digestion, indicating that the p25 polypeptide can exit the
      endoplasmic reticulum (ER) and is transported at least to the cis-Golgi
      compartment. Second, treatment of class II MHC-positive B cells with leupeptin
      blocks the formation of p25, further indicating that this Ii fragment is
      generated in the endosomal compartment. The role of the p25 Ii species in the
      assembly of complexes between peptides and DR molecules was then investigated.
      While the p25 fragment was totally unable to prevent binding of a synthetic
      tetanus toxin peptide to DR molecules, the full-length Ii species (p33/35)
      effectively inhibited peptide binding, indicating that, by contrast with the
      p33/35 species, the p25 fragment does not occlude the peptide binding site of DR
      molecules. We concluded that the p25 fragment, which is produced by proteolytic
      cleavage at the N-terminal side of Methionine 107, has a decreased affinity for
      DR molecules as compared with the p33/35 species. Dissociation of the p25
      fragment from DR molecules exposes the peptide binding site, which is thus made
      accessible for antigen fragments. This model of the complexes between DR and
      antigen fragments proposes that a stretch of Ii prevents peptide binding by
      occluding the peptide binding site without directly occupying it.

PMID- 8272077
TI  - OH. treatment of tetanus toxin reduces its susceptibility to limited proteolysis
      with more efficient presentation to specific T cells.
AB  - At inflammatory sites, before their processing, antigens are exposed to oxygen
      free radicals released by activated cells. The effect of hydroxyl radicals (OH.)
      on the structure of a protein antigen, tetanus toxin (TT) was investigated, as
      well as the consequences on processing and presentation. A chemical system
      composed of Fe-EDTA, ascorbate and H2O2 was used to produce physiological amounts
      of OH. radicals. TT exposed to OH. radicals presented a marked decrease of its
      intrinsic fluorescence with a concomitant increase of the content of bityrosine,
      but no fragmentation of the protein was detected by SDS-PAGE. Processing of the
      modified TT was analysed, by incubating TT at acidic pH with fractions enriched
      in plasma membranes and lysosomes obtained from a lymphoblastoid cell line (LCL).
      Proteolysis of OH.-treated TT was less important than proteolysis of native TT,
      especially upon prolonged incubations. Oxidized TT presented by LCL cells induced
      a greater proliferation of three different TT specific T cell clones, compared to
      native TT. When proteolytic digests of TT were presented by fixed LCL cells to a
      homologous T cell line, the proliferative response obtained in the presence of
      digests of OH.-treated TT was sustained, even in the case of prolonged
      proteolysis, whereas the response to digests of native TT fell rapidly. The
      relative resistance of OH.-treated TT to proteolysis appears thus responsible for
      its greater presentation to specific T cells, probably by protecting epitopes.

PMID- 8272079
TI  - Molecular structural studies of effector functions of a mouse immunoglobulin G
      that lacks the entire CH1 domain: small-angle X-ray scattering, nanosecond
      fluorescence depolarization and stable isotope-aided NMR analyses.
AB  - Molecular structural studies are reported of a short-chain mouse IgG2a antibody
      that lacks the entire CH1 domain. We have recently shown that (1) this short
      chain antibody comprises two components in which the inter light-chain disulfide
      bridge does and does not exist, and (2) these two components are different in the
      constitutive complement-activating activity [Mizutani et al. (1993) J. Immunol.
      150, 131-138]. Structures were compared for these two components on the basis of
      small-angle X-ray scattering, nanosecond fluorescence depolarization and isotope
      aided NMR data. It has been discussed how the presence and absence of the inter
      light-chain disulfide bridges affect the complement-activating activity of the
      two components of the short-chain antibody.

PMID- 8272078
TI  - Cloning, expression and characterization of a murine-human chimeric antibody with
      specificity for pre-S2 surface antigen of hepatitis B virus.
AB  - The cloning, expression and characterization of a murine-human chimeric antibody
      with specificity for the pre-S2 surface antigen (Ag) of hepatitis B virus (HBV)
      is described. The heavy and light chain variable region (VH and VL) genes
      encoding the murine monoclonal antibody (mAb) were isolated and combined with
      human gamma 1 and kappa constant region genes, respectively. The expression
      vectors containing the chimeric heavy and light chain genes were sequentially
      electroporated into murine Sp2/0 hybridoma cells and transfectomas secreting
      chimeric antibody were isolated. The chimeric antibody was purified and
      characterized by ELISA, Western analysis and competition immunoassay,
      demonstrating that the transfectoma functionally express and secrete murine-human
      chimeric antibody which retained the specificity and affinity of the parental
      murine mAb.

PMID- 8272080
TI  - In vitro translation of RNA from the German cockroach Blattella germanica.
AB  - The translation of mRNA within total RNA of German (Blattella germanica)
      cockroaches was performed using a rabbit reticulocyte lysate system. Analysis of
      the translation products by SDS-PAGE and combined autoradiography revealed
      several synthesized proteins with apparent molecular weights ranging from 20 kD
      to 110 kD. SDS-PAGE/Western blotting of non-radiolabeled translation products and
      incubation with human serum with IgE to cockroach allergens showed the presence
      of a 36 kD and 50 kD allergen. The confirmation of the translation of the
      cockroach allergens from total RNA is an important first step in the cloning of
      cockroach allergens.

PMID- 8272081
TI  - Early supplementary feeding and cognition: effects over two decades.
AB  - The study reported in this Monograph of the effects of early supplementary
      feeding on cognition included two data collection periods: a longitudinal
      investigation spanning the years 1969-1977 and a cross-sectional follow-up
      carried out in 1988-1989. The study was conducted in four rural villages in
      Guatemala and compared the differential effects of exposure in childhood (0-7
      years) to an Atole supplement (11.5 g of protein; 163 kcal) or a Fresco
      supplement (59 kcal) on performance on a battery of psychoeducational and
      information-processing tests in adolescence and young adulthood (11-24 years). In
      this report, particular attention is given to a cohort of subjects who were
      exposed to the supplement prenatally and during at least the first 2 years of
      postnatal life. Data on this subsample are contrasted with those on a cohort of
      subjects who received the supplement only after 24 months of life. The Monograph
      also reports results from an analysis of the supplementation effects in infancy
      and early childhood. Consistent differences between groups on the
      psychoeducational tests were observed. Adolescents from Atole villages scored
      significantly higher on tests of knowledge, numeracy, reading, and vocabulary
      than Fresco subjects. Atole was also associated with a faster reaction time in
      information-processing tasks. Significant interactions helped identify two groups
      who benefited more from the Atole treatment: those at the lowest levels of
      socioeconomic status and those who attained the highest levels of primary
      schooling. The consistent differences in test performance established in the
      follow-up assessment contrast sharply with the few and less pronounced between
      group differences observed in the infancy and preschool periods. After close
      scrutiny of alternative hypotheses, it is concluded that nutritional differences
      provide the strongest explanation for the test performance differences observed
      in the follow-up between the subjects exposed to the Atole and those exposed to
      the Fresco supplement.

PMID- 8272082
TI  - Going beyond nutrition: nutrition, context, and development.

PMID- 8272083
TI  - Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial
      fluid from patients with Lyme arthritis.
AB  - BACKGROUND: Borrelia burgdorferi is difficult to detect in synovial fluid, which
      limits our understanding of the pathogenesis of Lyme arthritis, particularly when
      arthritis persists despite antibiotic therapy. METHODS: Using the polymerase
      chain reaction (PCR), we attempted to detect B. burgdorferi DNA in joint-fluid
      samples obtained over a 17-year period. The samples were tested in two separate
      laboratories with four sets of primers and probes, three of which target plasmid
      DNA that encodes outer-surface protein A (OspA). RESULTS: B. burgdorferi DNA was
      detected in 75 of 88 patients with Lyme arthritis (85 percent) and in none of 64
      control patients. Each of the three OspA primer-probe sets was sensitive, and the
      results were moderately concordant in the two laboratories (kappa = 0.54 to
      0.73). Of 73 patients with Lyme arthritis that was untreated or treated with only
      short courses of oral antibiotics, 70 (96 percent) had positive PCR results. In
      contrast, of 19 patients who received either parenteral antibiotics or long
      courses of oral antibiotics (> or = 1 month), only 7 (37 percent) had positive
      tests (P < 0.001). None of these seven patients had received more than two months
      of oral antibiotic treatment or more than three weeks of intravenous antibiotic
      treatment. Of 10 patients with chronic arthritis (continuous joint inflammation
      for one year or more) despite multiple courses of antibiotics, 7 had consistently
      negative tests in samples obtained three months to two years after treatment.
      CONCLUSIONS: PCR testing can detect B. burgdorferi DNA in synovial fluid. This
      test may be able to show whether Lyme arthritis that persists after antibiotic
      treatment is due to persistence of the spirochete.

PMID- 8272084
TI  - Electrical alternans and vulnerability to ventricular arrhythmias.
AB  - BACKGROUND: Although electrical alternans (alternating amplitude from beat to
      beat on the electrocardiogram) has been associated with ventricular arrhythmias
      in many clinical settings, its physiologic importance and prognostic implications
      remain unknown. METHODS: To test the hypothesis that electrical alternans is a
      marker of vulnerability to ventricular arrhythmias, we developed a technique to
      detect subtle alternation in the morphologic features of the electrocardiogram
      (which would not be detectable by visual inspection of the electrocardiogram). In
      a group of 83 patients referred for diagnostic electrophysiologic testing, we
      prospectively examined whether levels of alternans predicted vulnerability to
      arrhythmias as defined by the outcome of electrophysiologic testing and
      arrhythmia-free survival. RESULTS: Sustained ventricular arrhythmias were induced
      during electrophysiologic testing in 32 of the patients (39 percent). In this
      group, low-level electrical alternans (a beat-to-beat change in amplitude of < 15
      microV) was detected over a broad range of physiologic heart rates (from 95 to
      150 beats per minute) and primarily involved the ST segment and the T wave (i.e.,
      the phase of repolarization). Alternans during repolarization was a significant
      and independent predictor of inducible arrhythmias on electrophysiologic testing
      (sensitivity, 81 percent; specificity, 84 percent; relative risk, 5.2). Of 66
      patients followed for up to 20 months, 13 had arrhythmic events. Alternans
      affecting the T wave and inducibility of ventricular arrhythmias were significant
      and essentially equivalent predictors of survival without arrhythmia (P < 0.001).
      Actuarial survival without arrhythmia at 20 months was significantly lower among
      the patients with T-wave alternans (19 percent) than among the patients without T
      wave alternans (94 percent). CONCLUSIONS: Electrical alternans affecting the ST
      segment and T wave is common among patients at increased risk for ventricular
      arrhythmias. Subtle electrical alternans on the electrocardiogram may serve as a
      noninvasive marker of vulnerability to ventricular arrhythmias.

PMID- 8272085
TI  - Results of conservative management of clinically localized prostate cancer.
AB  - BACKGROUND: The selection of treatment for patients with localized prostate
      cancer requires reliable information about the outcome of conservative
      management. Previous studies of this question are generally considered unreliable
      because they were uncontrolled and nonrandomized. METHODS: We performed a pooled
      analysis of 828 case records from six nonrandomized studies, published since
      1985, of men treated conservatively (with observation and delayed hormone therapy
      but no radical surgery or irradiation) for clinically localized prostate cancer.
      A Cox regression analysis was performed to determine which factors influenced
      survival among patients who did not die of causes other than prostate cancer
      (disease-specific survival). Kaplan-Meier curves for overall and metastasis-free
      survival among such patients were compared with use of the log-rank method and
      the Mantel-Haenszel test. RESULTS: Factors that had a significant effect on
      disease-specific survival were grade 3 tumors (risk ratio, 10.04), residence in
      Israel (risk ratio, 2.48) or New York (risk ratio, 0.37), and age under 61 years
      (risk ratio, 0.32). Ten years after diagnosis, disease-specific survival (with
      data on men who died from causes other than prostate cancer censored) was 87
      percent for men with grade 1 or 2 tumors and 34 percent for those with grade 3
      tumors; metastasis-free survival among men who had not died of other causes was
      81 percent for grade 1, 58 percent for grade 2, and 26 percent for grade 3
      disease. These findings were not affected by the inclusion of men who had early
      stage cancer, were older, had worse-than-average health, or underwent delayed
      radiation therapy or radical prostatectomy. CONCLUSIONS: The strategy of initial
      conservative management and delayed hormone therapy is a reasonable choice for
      some men with grade 1 or 2 clinically localized prostate cancer, particularly for
      those who have an average life expectancy of 10 years or less. New treatment
      strategies are needed for men with grade 3 prostate cancer.

PMID- 8272086
TI  - Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal
      nocturnal hemoglobinuria.
AB  - BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder in
      which there is a deficiency in the synthesis by hematopoietic cells of the
      glycosyl-phosphatidylinositol molecules that anchor proteins to the cell
      membrane. Recently, we demonstrated that a gene termed PIG-A (for
      phosphatidylinositol glycan class A), a component of glycosyl
      phosphatidylinositol biosynthesis, was responsible for PNH in two patients. The
      present study was undertaken to elucidate whether PIG-A is the gene responsible
      for all cases of PNH and to characterize further the somatically acquired
      abnormalities of this gene. METHODS: We studied granulocytes from 15 patients
      with PNH. The cell content of CD55 and CD59 was assessed by fluorescence
      activated flow cytometry. PIG-A transcripts were reverse-transcribed, amplified
      by the polymerase chain reaction, and cloned into plasmids. The structure of the
      cloned complementary DNA was analyzed by nucleotide sequencing, and its function
      was assessed on the basis of its ability to restore to normal the abnormal
      phenotype of a PIG-A-deficient cell line after transfection. RESULTS: Three
      patients had size abnormalities of PIG-A transcripts with different patterns, and
      in one patient a very low level of the PIG-A transcript was found. Eleven
      patients had transcripts of normal size, but the transfection assay revealed that
      in each patient some of them were nonfunctional. The percentage of nonfunctional
      PIG-A transcripts was correlated with the percentage of affected granulocytes (P
      < 0.001). Sequence analysis demonstrated somatic mutations in two of the
      patients. CONCLUSIONS: PIG-A is the gene responsible for PNH in all patients
      studied to date.

PMID- 8272087
TI  - Images in clinical medicine. Clostridium difficile.

PMID- 8272088
TI  - Oral azole drugs as systemic antifungal therapy.
AB  - The oral azole drugs--ketoconazole, fluconazole, and itraconazole--represent a
      major advance in systemic antifungal therapy. Among the three, fluconazole has
      the most attractive pharmacologic profile, including the capacity to produce high
      concentrations of active drug in cerebrospinal fluid and urine. Ketoconazole, the
      first oral azole to be introduced, is less well tolerated than either fluconazole
      or itraconazole and is associated with more clinically important toxic effects,
      including hepatitis and inhibition of steroid hormone synthesis. However,
      ketoconazole is less expensive than fluconazole and itraconazole--an especially
      important consideration for patients receiving long-term therapy. All three drugs
      are effective alternatives to amphotericin B and flucytosine as therapy for
      selected systemic mycoses. Ketoconazole and itraconazole are effective in
      patients with the chronic, indolent forms of the endemic mycoses, including
      blastomycosis, coccidioidomycosis, and histoplasmosis; itraconazole is also
      effective in patients with sporotrichosis. Fluconazole is useful in the common
      forms of fungal meningitis--namely, coccidioidal and cryptococcal meningitis. In
      addition, fluconazole is effective for selected patients with serious candida
      syndromes such as candidemia, and itraconazole is the most effective of the
      azoles for the treatment of aspergillosis.

PMID- 8272089
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 4-1994. A 38-year-old man with AIDS and the recent onset of
      diarrhea, hematochezia, fever, and pulmonary infiltrates.

PMID- 8272090
TI  - Lyme disease--where's the bug?

PMID- 8272091
TI  - PIG-A--the target gene in paroxysmal nocturnal hemoglobinuria.

PMID- 8272092
TI  - Progress in psychiatry.

PMID- 8272093
TI  - Progress in psychiatry.

PMID- 8272094
TI  - The treatment of ventricular tachyarrhythmias.

PMID- 8272095
TI  - The treatment of ventricular tachyarrhythmias.

PMID- 8272096
TI  - Enhanced atrioventricular conduction during atrial flutter after intravenous
      adenosine.

PMID- 8272097
TI  - On-site cardiac catheterization facilities and the use of coronary angiography
      after myocardial infarction.

PMID- 8272098
TI  - On-site cardiac catheterization facilities and the use of coronary angiography
      after myocardial infarction.

PMID- 8272099
TI  - Prehospital thrombolytic therapy for myocardial infarction.

PMID- 8272100
TI  - Thrombolytic agents.

PMID- 8272101
TI  - Tick-borne diseases.

PMID- 8272102
TI  - Human ehrlichiosis in New England.

PMID- 8272103
TI  - Review of methods in "breast augmentation: a risk factor for breast cancer?".

PMID- 8272104
TI  - Doctors vs. lawyers: round two.

PMID- 8272105
TI  - Doctors vs. lawyers: round two.

PMID- 8272106
TI  - Doctors vs. lawyers: round two.

PMID- 8272107
TI  - Doctors vs. lawyers: round two.

PMID- 8272108
TI  - Lessons from an inconvenient patient.

PMID- 8272109
TI  - State of affairs: the U.S.-Iran medical exchange program. Then and now.

PMID- 8272110
TI  - The cost of violence. The economy of health care delivery for non-accidental
      trauma in an urban southeastern community.

PMID- 8272111
TI  - Maternal mortality in North Carolina.

PMID- 8272112
TI  - Cancer awareness.

PMID- 8272113
TI  - Is there a right to health care?

PMID- 8272114
TI  - Thoughts on reading "Is there a right to health care?" A response to Professor
      Tong's article.

PMID- 8272115
TI  - The psoas signs. Well-described but often forgotten physical examination findings
      of iliopsoas inflammation.

PMID- 8272116
TI  - When God was tired: clozapine overdose.

PMID- 8272117
TI  - Tardive dyskinesia and pseudo-parkinsonism. In a nursing home patient who itched.

PMID- 8272118
TI  - [Ruptured aneurysm of the abdominal aorta with a clinically misleading picture].

PMID- 8272119
TI  - [An unstable mutation as cause of myotonic dystrophy].

PMID- 8272120
TI  - [Dyslexia as a cerebral functional disorder].

PMID- 8272121
TI  - [Antimicrobial treatment using beta-lactam antibiotics: continuous infusion
      appears to be sensible].

PMID- 8272122
TI  - [Introduction of advanced medical equipment in the home situation].

PMID- 8272123
TI  - [Continuous intravenous antibiotic home treatment in 11 patients with cystic
      fibrosis in The Northern Netherlands].
AB  - OBJECTIVE: Assessment of intravenous home treatment of respiratory infections of
      cystic fibrosis (CF) patients. SETTING: Provinces Groningen, Drente, Friesland
      and Overijssel. DESIGN: Open study. PATIENTS AND METHODS: Eleven CF patients,
      aged 10 to 28 years participated. Thirty episodes of home i.v. treatment with
      antibiotics were arranged. Differences in vital capacity (VC) and forced
      expiratory volume in one second (FEV1) and in body weight before and after
      treatment were compared with the same variables obtained during hospitalisation
      in the year before they were treated at home. Adverse events during home
      treatment were recorded. RESULTS: No differences were noted in changes in VC,
      FEV1 and body weight between home and hospital treatments. During 30 episodes of
      home treatment a new intravenous catheter had to be implanted only twice.
      CONCLUSION: In these 11 patients, intravenous treatment of respiratory infections
      at home was as efficacious as in hospital. No serious adverse events were
      observed.

PMID- 8272124
TI  - [Continuous intravenous home treatment of airway infections using ceftazidime
      administration via portable pump in patients with cystic fibrosis; a multicenter
      study].
AB  - OBJECTIVE: To study the feasibility and applicability of Home intravenous
      antibiotic treatment (HIVAT) in cystic fibrosis (CF) patients in the Netherlands.
      DESIGN: Prospective, multicentre study in CF patients with an exacerbation of a
      Pseudomonas aeruginosa pulmonary infection using a computerised, ambulatory pump
      for continuous infusion. METHOD: The effects of HIVAT were studied during one
      year in 24 CF patients (9 male, 15 female; mean age 23.3 years, range 7-52), who
      received a total of 39 courses of continuous ceftazidime 100 mg/kg/24 hrs i.v.
      for 3 weeks delivered by a pump. The treatment was preceded by a 2-3 days in
      hospital instruction period. The treatment was supervised by the clinic without
      home visits. Clinical data and quality of life questionnaires were collected at
      the start and at the end of treatment and one month later. Statistical analysis
      was performed using Wilcoxon's rank-sum test for paired samples. RESULTS: No
      major problems were encountered. The patients as well as their physicians
      preferred home treatment over in-hospital treatment. 35 out of 37 evaluable
      courses in 23 patients were efficacious. There were statistically significant
      improvements in clinical condition and quality of life during the treatment. This
      improvement lasted at least until one month after the end of treatment. The costs
      of HIVAT were 48-63% less than the same antibiotic treatment in the hospital.
      CONCLUSION: HIVAT was feasible and could be applied without major problems in the
      Netherlands. It proved safe, efficacious and cost-effective.

PMID- 8272125
TI  - [Partial instead of complete splenectomy in children for the pathological staging
      of Hodgkin disease].
AB  - OBJECTIVE: Evaluation of partial splenectomy in children for pathological staging
      of Hodgkin's disease. DESIGN: Prospective clinical study. PLACE: University
      Hospital Groningen. METHOD: From 1982 to 1988, 12 children with Hodgkin's disease
      underwent partial splenectomy during laparotomy for pathological staging. A
      follow-up of these children was conducted up for a median of 6 years (range 4-10)
      postoperatively. RESULTS: The median hospital stay after the laparotomy was 7
      days. There was no postoperative mortality; one patient needed a relaparotomy.
      During a median follow-up of 6 years, one patient died of secondary leukaemia.
      All the other children were well. None of the patients developed sepsis and no
      Howell-Jolly bodies could be found in their blood. CONCLUSION: Partial
      splenectomy for pathological staging of Hodgkin's disease is a safe procedure
      which causes hardly any underestimation of the stage of the disease and which
      ensures adequate spleen function, depending on the treatment used for Hodgkin's
      disease.

PMID- 8272126
TI  - [Pelizaeus-Merzbacher disease].
AB  - Two cases of Pelizaeus-Merzbacher disease are described, one with the classical
      and one with the connatal form, both in the same family. It is an X-linked
      disease affecting the myelinisation of the brain. Pelizaeus-Merzbacher manifests
      itself within a few months after birth and has a progressive character. The
      disease is caused by a point mutation in the PLP gene coding for the myelin
      protein proteolipid protein. MRI imaging has improved the possibility for
      diagnosis especially in families with cases of Pelizaeus-Merzbacher disease and
      PLP gene detection has brought antenatal diagnosis in focus.

PMID- 8272127
TI  - [Galactorrhea and gynecomastia as side effect of drugs].
AB  - Galactorrhoea or gynaecomastia are common and innocent phenomena, especially in
      certain age groups. Sometimes, however, they are secondary to serious diseases
      such as hormone producing tumours. Furthermore, a wide variety of drugs may in
      different ways induce galactorrhoea or gynaecomastia. A good knowledge of these
      drugs may prevent unnecessary anxiety and investigations. In spite of an
      abundance of often anecdotal reports scattered in the literature, little
      information is available on the identity of the most important drugs causing
      galactorrhoea or gynaecomastia in medical practice. The country-wide network of
      regional centres for intensified adverse drug reactions reporting of the
      Netherlands Pharmacovigilance Foundation LAREB can provide useful information on
      these and other side effects.

PMID- 8272128
TI  - [The 'pill' at the pharmacist: unfavorable for the safe use of drugs].

PMID- 8272129
TI  - [Reduction in the number of falls in hospitalized patients through the use of a
      risk-index and by preventive measures].

PMID- 8272130
TI  - [Reduction in the number of falls in hospitalized patients through the use of a
      risk-index and by preventive measures].

PMID- 8272131
TI  - [Reduction in the number of falls in hospitalized patients through the use of a
      risk-index and by preventive measures].

PMID- 8272132
TI  - [Intravenously administered immunoglobulins as a first-choice method in juvenile
      dermatomyositis].

PMID- 8272133
TI  - [Does no Helicobacter pylori mean no duodenal ulcer?].

PMID- 8272134
TI  - [Can the psychiatrist predict ability for driving?].

PMID- 8272135
TI  - [The many aspects pf the acid-fast rods].

PMID- 8272136
TI  - [May I introduce you...? 3 nursing home patients].

PMID- 8272137
TI  - [Home treatment of psoriasis using ultraviolet-B irradiation].

PMID- 8272138
TI  - [Stunning, preconditioning and hibernation; aspects of ischemia and reperfusion
      of the myocardium].

PMID- 8272139
TI  - [HIV-infection and diarrhea: diagnosis and treatment].

PMID- 8272140
TI  - [Obstetrical outcome in teenage pregnancies in The Netherlands].
AB  - OBJECTIVE: To compare the course of teenage pregnancies and deliveries with that
      in women between the ages of 20 and 29. DESIGN: Observational. SETTING: The
      Netherlands. METHOD: Using data from the 1989 National Obstetric Database (LVR),
      4500 teenage pregnancies were studied, to compare the risk of preterm birth, low
      birth weight and delivering a small for gestational age (SGA) baby between
      teenagers and older women. RESULTS: Women between the ages of 13 and 19 ran one
      and a half times as high a risk of having a preterm baby as women between the
      ages of 20 and 29 years (p < 0.0001). The risk of intrauterine death was 4 times
      as high for age 13-17 and 2 times as high for age 18-19 compared with older women
      (p < 0.0001). These results were found for teenage mothers of Dutch origin as
      well as for young mothers of foreign descent. Deliveries by teenagers were more
      often spontaneous, were of shorter duration and less often needed assistance than
      deliveries in older mothers (p < 0.001). CONCLUSION: Even in the Netherlands,
      with the lowest teenage pregnancy rate in the Western world and a prenatal care
      system generally considered of high quality, teenage pregnancies have less
      favourable outcomes than those in older women. Since we had no information on
      cultural background, socioeconomic status or life style, further research into
      determinants of outcomes of Dutch teenage pregnancies is indicated.

PMID- 8272141
TI  - [Prevalence of human T-cell lymphotropic virus type I among Dutch blood donors].
AB  - OBJECTIVE. To establish the prevalence of human T-lymphotropic virus (HTLV) type
      I among Dutch blood donors. DESIGN. Study to confirm screening results. SETTING.
      Central Laboratory of the Blood Transfusion Service of the Dutch Red Cross,
      section Virus Diagnostics, Amsterdam. METHOD. The majority (550,000) of the Dutch
      blood donors were tested in the course of 1993 for presence of HTLV antibodies.
      For serological confirmation using the Western Blot test, 20 of the 22 Dutch
      blood banks sent in blood samples of 714 donors found positive at HTLV screening.
      Material of 36 of these donors was suitable for testing using the polymerase
      chain reaction (PCR) for DNA of HTLV types I and II. RESULTS. The Western Blot
      confirmation test confirmed HTLV infection of 10 of the 714 blood donors; eight
      of these samples, examined with the PCR test, proved to be positive for DNA of
      HTLV I. In 537 of the 714 ELISA-reactive donors, the Western Blot test gave
      doubtful results. The PCR test for HTLV I/II DNA was negative in 26 of these
      samples, but the possibility could not be excluded that there were HTLV carriers
      among the other donors with a doubtful Western blot test result. With inclusion
      of the four donors infected with HTLV I that had been detected earlier, the
      prevalence of HTLV I among Dutch blood donors is found to be 1:39,000.

PMID- 8272142
TI  - [Characteristics of nursing home patients at initial admission: age, sex and
      morbidity].
AB  - INTRODUCTION: Some 35,000 new patients are admitted yearly to 'verpleeghuizen' or
      Dutch nursing homes. This paper describes some characteristics of these patients.
      METHOD: Data were collected using the national Nursing Home Registration System
      SIVIS of the Dutch centre for health care information. The response rate to the
      registration by the nursing homes is over 80%. RESULTS: Newly admitted nursing
      home patients are characterised by a (very) high age (over 50% of the patients
      are 80 years and over), a distribution of twice as many women as men and a
      morbidity pattern of chronic somatic and psychogeriatric, as well as orthopaedic
      disorders. CONCLUSION: Among elderly patients the nursing home patients
      constitute of a heterogeneous purpose of admission and morbidity pattern. Nursing
      home care focuses on rehabilitation, long-term care and terminal care.

PMID- 8272143
TI  - [Hypercalcemia caused by lithium medication in a female patient with a bipolar
      affective disorder].
AB  - In a 68-year-old woman, who used lithium carbonate because of longstanding
      recurring depression, an association was found between hypercalcaemia and the use
      of lithium. The serum calcium concentration appeared to be significantly
      correlated with the serum lithium concentration (y = 2.38 + 0.37x; r = 0.36; p =
      0.009). There was a significant inverse correlation between the ratio of 24-hour
      urinary calcium and creatinine excretion and the serum lithium concentration (y =
      0.80 - 0.22x; r = 0.43; p = 0.030). The association of hypercalcaemia and use of
      lithium has been reported before. The finding may be due to an effect of lithium
      on the parthyroids and (or) on the kidneys.

PMID- 8272144
TI  - [Postinfectious tropical malabsorption and the differences from non-tropical
      sprue (celiac disease)].
AB  - The clinical course is described of a 69-year-old patient with a malabsorption
      syndrome since her stay in Indonesia. Besides chronic diarrhoea and weight loss
      she suffered from malnutrition and had partial villous atrophy. Coeliac disease
      was considered in the differential diagnosis but considering the endemic
      appearance of postinfectious tropical sprue (PTS) in Indonesia and the extreme
      vitamin B12 deficiency our patient experienced, PTS appeared more likely. A good
      response to the therapy prescribed for PTS confirmed the diagnosis.

PMID- 8272145
TI  - [Greater value of sumatriptan over ergot alkaloids still not proven].

PMID- 8272146
TI  - Effect of 1-alkylpyrrolidine N-oxides on energy metabolism of cancer cells.
AB  - The main purpose of the present investigation was to study the effect of a
      homologous series of 1-alkylpyrrolidine N-oxides on ATP-producing processes in
      Ehrlich ascites and L1210 murine leukemia cells. The effect on aerobic glucose
      consumption, lactic acid formation, content of total (T-SH) and non-protein thiol
      groups (NP-SH), endogenous respiration and the level of ATP in tumor cells
      incubated in vitro was investigated. 1-Tetradecylpyrrolidine N-oxide (TPNO), one
      of the most active compounds, immediately after addition to the suspension of
      Ehrlich cells in an ice bath, decreased the level of ATP to the same extent over
      the whole concentration range. After 2 h incubation at 37 degrees C the drop in
      the ATP level was lower. The decrease in ATP level might be explained through the
      interaction of the amine oxide with the cell membrane integrity.

PMID- 8272147
TI  - New tumoricidal semisynthetic ether phospholipid, plasmanyl-(N-acyl)ethanolamine
      (PNAE(s)) and enhancement of its tumoricidal activity by calcium ions.
AB  - Recently we described a novel, nontoxic, natural ether phospholipid with
      selective antitumor activity, 1-0-alkyl-2-acyl-sn-glycero-3-phospho-(N
      acyl)ethanolamine, i.e., plasmanyl-(N-acyl)ethanolamine (PNAE), isolated from
      ischemic tissue of chick embryo. The chemical structure of PNAE has been
      confirmed by partial synthesis. The semisynthetic preparation PNAE(s), 1-0
      octadecyl-2-oleoyl-sn-glycero-3-phospho-(N-palmitoyl)ethanolamine, exhibited
      tumoricidal activity against human tumor cells T24 and mouse sarcoma cells Mcll
      as well as in vivo against murine sarcomas S-180 and Mcll. PNAE(s) selectively
      destroyed tumor cell membranes as has been demonstrated by scanning electron
      microscopy. The antitumor activity of PNAE(s) in vitro and in vivo was
      significantly enhanced by Ca2+ ions. These results may be explained by selective
      damage of tumor cell membranes by PNAE(s), increasing also the tumor cell
      membrane permeability for exogenous Ca2+ ions and altering the intracellular
      calcium homeostasis in tumor cells. By increased concentration of Ca2+ in tumor
      cell cytosol selective damage and lysis of tumor cells was induced. The combined
      use of parenteral administration of PNAE(s) and peroral doses of calcium
      gluconate may provide a new approach to enhancement of antitumor activity of
      PNAE(s) by Ca2+ in a very selective and nontoxic antitumor therapy.

PMID- 8272148
TI  - Evaluation of 2-(methylaminosulfonyl)-1-(arylsulfonyl)-1-methylhydrazines as
      anticancer agents.
AB  - Seven new 2-(methylaminosulfonyl)-1-(arylsulfonyl)-1-methylhydrazines were
      prepared. The anticancer activity of these compounds was assessed in murine
      Ehrlich ascites carcinoma (EAC) by in vivo screening. Moderate in vivo activity
      in EAC was exhibited by three compounds. All of them were screened in vitro
      against a battery of human tumor cell lines at the National Cancer Institute
      (NCI), USA. One of them, compound 3a has displayed highly significant specificity
      in the renal tumor cell line RXF 393. These three compounds were also assessed
      for in vitro anti-HIV activity at the NCI, however, they have not reached the
      criteria of significant activity. The alkylating activity of the compounds was
      determined by measuring the absorbance of the alkylated product of 4-(4
      nitrobenzyl)pyridine. It has been found that they are capable of acting as
      chemical alkylating agents.

PMID- 8272149
TI  - Effect of three biological response modifiers on chemical carcinogenesis in mice.
AB  - The modulation of chemical carcinogenesis by three biological response modifiers
      was assessed in a mouse model. CBA mice given 20-methylcholanthrene s.c. were
      treated with peptidoglycan monomer, azure B and indomethacin for one month,
      either from day 0 or 75 after methylcholanthrene injection to assess their
      effects on tumor incidence (on days 150 and 300), time of tumor appearance, time
      of death, and duration and dynamics of tumor growth. All three agents
      significantly influenced some of the parameters of tumor growth, except tumor
      incidence on day 300. Highly significant sex differences in tumor appearance and
      growth were observed. Tumors with late appearance grew faster in comparison to
      tumors with early appearance. The data presented indicate that the effectiveness
      of anti-cancer body defense mechanisms can be best defined by the time of tumor
      appearance.

PMID- 8272151
TI  - HPLC analysis of optical isomers of leucovorin and methotrexate using achiral
      chiral system.
AB  - Chiral high performance liquid chromatography was used for the enantiometric
      separation of leucovorin. The optimal separation conditions recommended after
      optimizing the mobile phase composition, flow rate, and temperature are
      described. Achiral reversed-phase chromatographic method was applied for the
      simultaneous separation of methotrexate and leucovorin in clinical samples.
      Column-switching system including achiral short pre-column and chiral analytical
      column based on immobilized bovine serum albumin were used for simultaneous
      determination of leucovorin and methotrexate patients treated at the National
      Cancer Institute.

PMID- 8272150
TI  - Vitamin E--its status and role in leukemia and lymphoma.
AB  - A comparative study has been performed on the relationship between vitamin E and
      immunofunction in normal and malignant condition in human and murine systems.
      Further, the effects of supplemental vitamin E on tumor take, host survival and
      tumor growth have been studied in a transplantable lymphoma in mice. Vitamin E
      was assayed in serum samples from normal subjects and from patients with leukemia
      and lymphoma by high performance liquid chromatography (HPLC). The murine group
      included Dalton's ascitic lymphoma (DL), Schwartz lymphoblastic leukemia (SVL)
      and Moloney lymphoblastic leukemia (MVL). Serum vitamin E was found to be lower
      than that of the normal controls in all cases of leukemia and lymphoma both in
      human and animal system. The levels of immunoglobulins (IgG and IgM) were found
      to be higher in mice with leukemia and lymphoma. Supplementary vitamin E
      administered at the initial phase of development of murine lymphomas reduced the
      rate of tumor growth, improved host survival and elevated serum vitamin E level.
      Vitamin E supplementation also activated specific mitogen induced blastogenesis
      of peripheral blood lymphocytes (PBL) and elevated serum IgG level. IgM remained
      unaltered and macrophage activity did not seem to be affected. The present
      findings indicated a low status of vitamin E in tumor bearing host and a
      beneficial effect of supplemental vitamin E on the host which was mediated by the
      host immune system.

PMID- 8272152
TI  - Estimation of reduction of life-time risk of cervical cancer through one life
      time screening.
AB  - The purpose of screening for cervical cancer is to prevent the appearance of
      invasive disease by the detection and treatment of precancerous lesions. Based on
      data from the developed countries, recommendations have been made regarding the
      age at which cytology screening should begin and the interval with which
      rescreening should be performed. However, these recommendations may not be
      applicable for a developing country like India due to human and financial
      resource constraints. WHO has recommended that for countries where resources are
      limited the aim should be to screen every woman at least once in her life-time at
      an appropriate age. Hence, it is essential to determine the age at which
      screening may be offered to derive maximum gains. With this in background, based
      on the data of national cancer registries, an attempt has been made for Indian
      population to estimate the reduction in the cumulative incidence rate of cervical
      carcinoma which can be achieved in a cohort of women aged 20-64 years by
      screening once in her life-time at an appropriate age. Our findings revealed that
      the first screening offered at 45 years of age could produce gains to the extent
      of 20-27%, while the screening offered at 50 or 55 years produced the maximum
      gains to the extent of 25-29%. However, keeping in view the produce years of
      lives lost in younger women, it may be reasonable to offer once in life-time
      screening to women aged 45 years.

PMID- 8272153
TI  - Amelioration of doxorubicin cardiotoxicity by the bispiperazinedione ICRF-187 in
      women with advanced breast cancer: a preliminary report.

PMID- 8272154
TI  - A novel cell growth-promoting factor identified in a B cell leukemia cell line,
      BALL-1.
AB  - A novel leukemia cell growth-promoting activity has been identified in the
      culture supernatant from a human B cell leukemia cell line, BALL-1. The
      supernatant from unstimulated cultures of the BALL-1 cells significantly promoted
      the growth of 16 out of 24 leukemia/lymphoma cell lines of different lineages (T,
      B and non-lymphoid) in a minimal concentration of fetal bovine serum (FBS), and
      of 5 out of 12 cases of fresh leukemia cells in FBS-free medium. The growth
      promoting activity in the BALL-1 supernatant has been further characterized using
      FPLC chromatography, molecular weight (MW) sieve filtration and dialysis. The MW
      of the factor was less than 10 kDa. The growth-promoting activity was heat and
      acid stable and resistant to trypsin treatment. The factor isolated from the BALL
      1 supernatant was distinct from known polypeptide growth factors with MW below 10
      kDa, such as epidermal growth factor, transforming growth factor alpha, insulin
      like growth factor I (IGF-I), IGF-II and insulin, as determined by specific
      antibodies and by cell growth-promoting tests. The factor in the BALL-1
      supernatant did not promote the proliferation of normal human fresh peripheral
      blood lymphocytes or mouse fibroblast cell line, BALB/c3T3. In addition to the
      BALL-1 supernatant, a similar growth-promoting activity was found in the culture
      supernatants from 13 of 17 leukemia/lymphoma cell lines tested. The activity in
      these culture supernatants promoted the growth of leukemia/lymphoma cell lines in
      autocrine and/or paracrine fashions. These observations suggest that the low MW
      cell growth-promoting activity found in the BALL-1 culture supernatant is
      mediated by a novel factor which may well be responsible for the clonal expansion
      of particular leukemic clones.

PMID- 8272155
TI  - Leukemia-associated marker combinations in acute leukemia suitable for detection
      of minimal residual disease.
AB  - In the absence of truly leukemia-specific antigen, antigen combinations were
      identified in leukemia cells that are absent or extremely rare among normal
      hemopoietic cells. Some of the studied combinations related to the simultaneous
      surface and cytoplasmic marker expression, others, expressed mainly on cell
      surface membrane, represented atypical or aberrant combinations. Comparing
      membrane (m) and cytoplasmic (c) antigen expression (followed in 23 acute
      leukemia cases), we observed that CD3 could be detected in cytoplasm in the
      majority of T-ALL cells, while was absent on cell surface membrane where
      simultaneous expression of more immature T cell markers, such as CD7 and CD5,
      could be detected. Combination of mCD7/cCD3 could be regarded as a suitable
      marker of individual T-ALL cells. In cases of B-precursors of acute leukemia
      cells, leukemia-related combination of mCD19/cCD22 was found, which could
      characterize a single leukemia cell. The cells in one of 11 AML followed cases
      were positive for CD13 in cytoplasm, but not on cell surface membrane, where CD33
      and other myeloid antigens were expressed. The cells in another two AML cases
      were positive for CD11 in cytoplasm but not on cell surface membrane, where CD13
      or CD33 were expressed. Again, marker combinations of mCD33/cCD13 and mCD13 or
      mCD33/cCD11, respectively, represent a leukemia-related feature, suitable for
      tracing single leukemia cells in double immunofluorescence. Acute leukemia
      defined by the coexpression on most blast cells of antigens classically
      attributed to different lineages (referred as atypical/aberrant marker
      combinations) remains a rare event. We isolated a series of 27 (12%) such cases
      of 225 acute leukemia patients whose cells were immunophenotyped at diagnosis.
      Myeloid markers were present in T-ALL of two cases, T and B markers were
      coexpressed in 13 cases, markers of B and myeloid lineage were associated in one
      case, and T cell and myeloid antigens were found in 10 AML cases; in one AML case
      (M3 according to FAB classification) an aberrant nuclear coexpression of TdT was
      observed. In one case of the last group an interesting antigen combination of
      CD4/CD34 present in AML with monocytic differentiation was observed. When 5
      patients with leukemia-associated (aberrant) markers were again analyzed at
      relapse, the relevant antigen combinations were retained in all of them. In
      summary, 44 of 50 cases (88%) from our acute leukemia series studied for leukemia
      associated antigen combination, both with surface membrane and cytoplasmic marker
      combinations and those with aberrant markers coexpression allow the detection of
      minimal residual disease.

PMID- 8272156
TI  - Potentiation of cis-DDP and pyridoxal effect on isolated DNA during simultaneous
      application.
AB  - Pyridoxal and cis-diamminedichloroplatinum (II) (cis-DDP) have a different mode
      of interaction with DNA. Cis-DDP caused extensive transforming inactivation of
      pBR322 DNA but did not form strand breaks in DNA molecules. On the other hand,
      pyridoxal formed frank strand breaks in the DNA chains and decreased DNA
      transforming activity. A higher level of DNA transforming inactivation was
      obtained during simultaneous application of both compounds than would be an
      additive effect of these compounds applied to DNA independently. This synergistic
      effect can be ascribed to the introduction of thermolabile sites by the combined
      action of cis-DDP and pyridoxal. These lesions were converted by heat-treatment
      to DNA strand breaks and detected electrophoretically. Using two different
      methods, cis-DDP and pyridoxal, during simultaneous application, interacted with
      DNA with higher efficiency.

PMID- 8272157
TI  - In vitro antiproliferative effect of interferon alpha in solid tumors: a
      potential predictive test.
AB  - An in vitro test for the antiproliferative effect of human leukocyte interferon
      (IFN-alpha) was performed in primary cultures of tumor cells obtained from 32
      patients with either malignant melanoma (13), renal carcinoma (4) or bladder
      carcinoma (15). Our results demonstrated activity of IFN in all three groups of
      solid tumors. However, appreciable differences in sensitivity to
      antiproliferative effect of IFN between individual tumors of the same type were
      found. The potential of this antiproliferative test for prediction of treatment
      response in IFN-therapy is discussed.

PMID- 8272158
TI  - Humoral immunity in patients with carcinoma of the uterine cervix--effects of
      radiation therapy.
AB  - The parameters of nonspecific immunity-serum immunoglobulins and immune complexes
      -were evaluated in patients with carcinoma of the uterine cervix (Stages IIB and
      IIIB) prior to, during and immediately after pelvic irradiation. In untreated
      patients, significantly elevated circulating IgA was found only in patients in
      Stage IIIB; serum IgG and IgM in both groups did not differ from control values.
      The level of circulating immune complexes in both groups was higher than in
      controls. Radiotherapy did not affect significantly any of the parameters
      examined; only the percentage of patients with elevated concentrations of IgA and
      IgG decreased during the treatment. These results showed that fractionated pelvic
      irradiation did not affect B cell function, these cells being more radioresistant
      than other lymphocyte subpopulations.

PMID- 8272159
TI  - Tissue polypeptide antigen in bronchogenic carcinoma.
AB  - Serum concentrations of tissue polypeptide antigen (TPA) were examined by an
      immunoradiometric technique in 114 patients with bronchogenic carcinoma and in 55
      patients with noncancerous lung diseases. The sensitivity of TPA examination in
      bronchogenic carcinoma was 67.5% and was increased in advanced stages of the
      disease. No statistically significant differences were observed between
      histologic types of bronchogenic carcinoma. In nonmalignant lung diseases,
      elevated levels of TPA were observed in 21.8% of patients. TPA is of little value
      in the diagnosis of bronchogenic carcinoma; however, it may be useful as an
      auxiliary criterion for staging.

PMID- 8272160
TI  - Usefulness of a multiple biomarker assay in bronchoalveolar lavage (BAL) and
      serum for the diagnosis of small cell lung cancer.
AB  - To evaluate the diagnostic usefulness of simultaneous determinations of
      carcinoembryonic antigen (CEA), neuron specific enolase (NSE), chorionic
      gonadotrophin (HCG) and carbohydrate antigenic determinant 19-9 (CA 19-9), we
      studied 48 patients with small cell lung carcinoma (SCLC) and 15 with
      nonmalignant lung disease. The combination of CEA-BAL, NSE-BAL, and NSE-serum
      taken together with results of bronchoscopy (histologic and cytologic) showed the
      highest discriminating power between malignant (SCLC) and nonmalignant lung
      disease. The sensitivity of bronchoscopy alone was 35%. However, when
      bronchoscopy results were combined with 3 positive markers, the sensitivity
      increased to 71%, with at least 2 positive markers to 94%, and with at least 1
      positive marker to 100%. When both bronchoscopy and all 3 markers were negative,
      the results showed a negative predictive value of 100%.

PMID- 8272161
TI  - Gastric mucosal antioxidant activity in patients at increased risk of gastric
      cancer.
AB  - In 68 subjects the activities of Cu/Zn-superoxide dismutase (SOD), catalase (CAT)
      and glutathione peroxidase (GSH-Px) were investigated in gastric mucosa. The
      patients were classified according to the histological finding into following
      groups: 12 with normal finding (N), 16 with superficial gastritis (SG), 13 with
      mild atrophic gastritis (MAG), 19 with severe atrophic gastritis (SAG) and 8 with
      gastritis after partial gastrectomy (PGG). The comparison of groups SG, MAG, SAG
      and PGG with the group N revealed the following changes: in SG increased SOD and
      GSH-Px, in MAG and SAG no significant changes, and in PGG increase in SOD, CAT
      and GSH-Px were observed. It was supposed that increased enzymatic activities
      were caused by higher concentration of active oxygen species produced by
      phagocytizing leukocytes in inflamed gastric mucosa. Administration of vitamin E
      resulted in significant reduction of SOD and CAT activities, on the other hand
      GSH-Px activity significantly increased. The explanation of this effect of
      vitamin E requires further studies. A prolonged interaction of active oxygen
      species with chemical carcinogens (N-nitroso- or diazonium compounds, PAH) can
      exhibit a significant promoting effect on the development of intestinal type of
      gastric cancer from its precancerous conditions, above all after partial
      gastrectomy.

PMID- 8272162
TI  - Comparability of results of postnatal and long-term tests for carcinogenicity.
AB  - A method of testing postnatal carcinogenicity in rats was elaborated. The
      substances to be tested were administered from the 1st day after birth to the
      5th, 10th and 20th days of age. The subsequent supply of a substance in diet from
      weaning (28th day of age) up to the end of the first year of survival was an
      optimal combination. A total of 12 substances were tested by this method. For all
      substances it was possible to provide a comparison with the results of long-term
      studies. For nine substances carcinogenicity was demonstrated in both tests, out
      of them in eight cases in identical organ systems. In three cases no
      carcinogenicity was ascertained in the postnatal study, in two compounds
      identical negative results were obtained by the two approaches. In one case (the
      cytostatic TS-160) development of sarcomas was found at the site of subcutaneous
      administration in the long-term study, and this effect was not observed in the
      postnatal study. Results identical for the two methods (carcinogenic or
      noncarcinogenic) were achieved in 11 substances, i.e. 91.7%. In addition, in 10
      compounds, for which carcinogenicity was demonstrated either in the postnatal
      study or in the long-term study, the occurrence of tumors was found in identical
      organ systems after 8 compounds which is an 80% agreement. In mice, this identity
      of organs was demonstrated only in 62.5% of the compounds tested. The present
      results demonstrated that the use of postnatal carcinogenicity test in rats
      offers the determination of possible carcinogenic effect of the compound tested
      with a high probability, under economically more advantageous conditions, and
      with almost the same qualitative results as with the use of the long-term tests
      for carcinogenicity.

PMID- 8272163
TI  - Bilateral germ cell tumors of the testis.
AB  - In a retrospective study of 530 patients with testicular germ cell tumors treated
      between 1977 and 1993, a group of 12 patients (2.26%) with bilateral testicular
      tumors was analyzed. While bilateral tumors were simultaneously present in two
      cases (both with different histologic types), consecutive development of a tumor
      in the contralateral testis was observed in 10 patients 5.25 years (range, 3-13.5
      years) after orchiectomy for the first tumor. The authors highlight the
      variability of histologic types in both testes, the need for an individual
      therapeutic approach with a view to previous therapy for the first tumor, the
      need for hormonal replacement as well as the possibility of testicular prosthesis
      implantation following bilateral orchiectomy.

PMID- 8272164
TI  - Soft tissue sarcomas: thirteen years experience in the service of medical
      oncology of a general hospital.
AB  - Thirty-seven patients with soft tissue sarcomas were treated between 1981 and
      1990. All of them were operated. Thirteen patients with marginal resection
      received adjuvant radiotherapy. Radiotherapy decreased the rate of local
      relapses. Sixteen patients received adjuvant chemotherapy with ifosfamide
      epirubicin and four of them had a recurrence. Twenty-one patients did not receive
      chemotherapy and 13 of them relapsed. Adjuvant chemotherapy improved the disease
      free survival during the first year, but not benefit appeared in long-term
      disease-free survival and overall survival.

PMID- 8272165
TI  - [Diagnosis of recurrent intervertebral disk prolapse with nuclear magnetic
      resonance tomography].
AB  - Persisting low back pain after lumbar discectomy may have many reasons.
      Reoperation is likely to be successful if a recurrent disc prolapse is found. The
      sensitivity and validity of diagnostic tools used cannot as yet be considered to
      be optimal. For this reason in our study 130 patients who were supposed to have a
      recurrent disc herniation underwent MRI with and without application of
      Gadolinium DTPA. In all patients we saw enhancement in the spinal canal.
      Sensitivity of MRI as verified by reoperation was > 90%. Hence, we can recommend
      this diagnostic tool for the diagnosis of recurrent disc herniation.

PMID- 8272166
TI  - Signal intensity of brain metastases on T2-weighted images: specificity for
      metastases from colonic cancers.
AB  - In this report, we present and discuss the signal intensity of brain metastases
      from colon cancer on both T1- and T2-weighted images. In five of 6 cases,
      metastases were seen as markedly hypointense areas on T2-weighted images. This
      finding should alert one to the possibility of a primary cancer of the colon.
      Some haemorrhagic metastases from other malignancies also showed marked
      hypointensity. They usually exhibited hyperintensity on T1-weighted images. A
      case of colon metastasis was also haemorrhagic, and in this case a hyperintense
      area was observed on T1-weighted images. The marked hypointense area corresponded
      to peripheral necrosis and probably some viable tumour. Aetiologically, such
      hypointensity was not induced by severe fibrosis, calcification or excessive iron
      deposition.

PMID- 8272167
TI  - [Intraventricular hemorrhage].
AB  - In the University Cantonal Hospital in Basel, 34 intraventricular hemorrhages
      were diagnosed by computer tomography from 1981 to 1990. The most frequent cause
      of bleeding into the ventricular system (35.3%) was rupture of an aneurysm,
      followed by hypertensive hemorrhages (23.5%). The cause of bleeding into the
      ventricular system could not be found in 20.6% of the cases investigated. The
      hemorrhage was present in all ventricles in 13 cases. A ruptured aneurysm was
      responsible for this in five patients. The hemorrhage was found in two and three
      ventricles in 11 cases. Only one ventricle was filled with blood in 10 cases;
      this was due to hypertensive hemorrhage in four patients. Besides open and
      enclosed ventricular drainage, aneurysm clipping was carried out in six cases,
      osteoplastic craniotomy in 12 cases and bore hole trepanation in four cases,
      depending on the underlying disease responsible for bleeding into the ventricular
      system. We were able to observe restitution of complete functional integrity at
      the follow-up examination one year later in eight cases (23.53% of all patients).
      Neurological deficits were shown at follow-up in 10 cases (= 29.41%). In our
      patients, the mortality was 47.1% (= 16 patients).

PMID- 8272168
TI  - The extreme lateral approach to thoracic disc herniations: technique and
      preliminary results.
AB  - The extreme lateral approach to the thoracic disc spaces produces minimum
      disruption of the normal spinal anatomy, avoids retraction of the spinal cord,
      and preserves the intercostal neurovascular bundle. It is achieved by removal of
      about 5 cm of the rib which has its insertion at the disc level, if necessary
      associated with partial removal of the transverse process, followed by partial
      pediculotomy and a limited lateral rachitomy (vertebral body resection), which
      permits the opening of the spinal canal exclusively ventral to the intervertebral
      foramen. The initial results of 6 patients, operated in up to four discs at the
      same occasion, are promising.

PMID- 8272169
TI  - [Ischemic lesions in the vertebral artery blood flow area as a rare complication
      of lumbar disk surgery].
AB  - We report on the case of a 61-year old man who developed a reversible Brown
      Sequard syndrome immediately after an uncomplicated lumbar discectomy. Magnetic
      resonance imaging showed ischaemic lesions in the upper cervical medulla, the
      caudal part of the medulla oblongata, and in the cerebellum. Vertebral artery
      compression due to spondylosis and hyperflexion of the cervical spine during
      operation is discussed as a possible pathogenetic mechanism.

PMID- 8272170
TI  - [Unusual course of glioblastoma multiforme as calcinosis in CCT].
AB  - We report about a rare case of multifocal bihemispheric glioblastoma (WHO grade
      IV) with unusual course: At time of histological diagnosis via open biopsy and
      subtotal tumor resection right parieto-occipital the tumorous lesion presents
      itself for nine months unchanged as a little calcification right parietal, before
      developing in CCT multiocular bihemispheric hyperdens-hypodens areals with margin
      contrast enhancement and perifocal edema within one month. Tumor histogenesis of
      this special case is discussed contrasting the embryogenetic concept with the
      concept of tumor-grading. From clinical relevance is the fact that even a long
      time unchanged unifocal calcification in CCT could be the first sign of
      developing glioblastoma, and so short-term clinical and computer tomographic
      controls are necessary.

PMID- 8272171
TI  - Malignant growth of a recurrent macroprolactinoma after radiation therapy.
AB  - The authors report a case of a 60-year-old woman with a macroprolactinoma. After
      radiation therapy of the subtotally excised recurrent tumor, it developed a rapid
      malignant-destructive growth with invasion into adjacent structures. The causal
      factors are discussed and the literature is briefly reviewed.

PMID- 8272172
TI  - [Embolization of cerebral arteriovenous malformations--methodology and clinical
      results].

PMID- 8272173
TI  - Vascular dementia: a time to 'seize the moment'.

PMID- 8272174
TI  - Smoking as a risk factor for cortical ischaemia presumably due to carotid
      occlusive disease.
AB  - Smoking is now a well established risk factor for ischaemic stroke. However, the
      risk associated with smoking may differ between subgroups of ischaemic stroke. To
      test the hypothesis that cortical ischaemia due to carotid artery occlusive
      disease, the latter of which has previously been linked to smoking, may have a
      higher smoking risk compared to other forms of cerebral ischaemia, we identified
      178 cases of cortical ischaemia presumably due to carotid occlusive disease in
      our previous case-control population and compared the odds ratios (OR) for
      smoking risk in this group with that in group of 244 cases of other forms of
      cerebral ischaemia combined. All cases were individually matched for age (+/- 5
      years) and sex with neighbourhood controls. Multiple conditional logistic
      regression was used to adjust for potentially confounding factors. The OR for
      current smokers in the cortical group was higher than that in the non-cortical
      group [OR 4.4, 95% confidence interval 2.2, 8.9 vs. 2.1 (1.1, 4.1)], particularly
      for those who smoked more than 60 pack-years [5.5 (2.2, 14.0) vs. 1.5 (0.6, 3.8)]
      and those who currently smoked more than one pack per day [20.2 (3.3, 122.3) vs.
      2.6 (0.8, 8.2)], but not significantly. Overall, there is some evidence to
      suggest that smoking may be a more potent risk factor for cortical than for other
      forms of cerebral ischaemia, particularly at high smoking rates. Further studies
      are needed to substantiate this finding.

PMID- 8272175
TI  - Stroke mortality in Spain, 1901-1986.
AB  - We studied the mortality from stroke as the underlying cause of death in Spain
      during the period 1901-1986. The age-adjusted mortality in 1986 was 114.4 per
      100,000 among males and 100.6 per 100,000 for females. From 1901 to 1986, the SMR
      from stroke in Spain decreased by approximately 2/3, levelling off during the
      period 1950-1970, and again falling from 1973 on. A new plateau might have been
      initiated in the early 1980s. Since 1950, a marked continuous decrease is seen
      for hemorrhagic stroke and, since 1973, for ischemic stroke. In spite of
      difficulties in interpreting death record data, this study confirms that stroke
      mortality in Spain ranks on a medium level when compared with data from other
      European countries and that it conforms to the patterns reported for industrial
      countries. The drop in stroke mortality since 1973 preceded the widespread use of
      antihypertensive drugs.

PMID- 8272176
TI  - Multiple sclerosis and blood transfusion.
AB  - It has recently been suggested that multiple sclerosis (MS) may be triggered by a
      retrovirally encoded superantigen. If true, then MS should be associated with
      risk factors that predispose to retroviral infection. Blood transfusions
      represent one such risk factor. 150 Scottish patients with 'clinically definite'
      or 'probable' MS and 150 age-/sex-matched neurological controls were questioned
      about blood transfusion. 7 (4.7%) of the patients and an equal number of controls
      had received a blood transfusion before the year of disease onset in the matched
      case (odds ratio 1.0, 95% C.I. 0.3-3.34). These results provide no evidence that
      blood transfusion is associated with an increased risk of MS.

PMID- 8272177
TI  - A community survey of neurological disorders in Saudi Arabia: the Thugbah study.
AB  - We report the findings of a total population survey of Thugbah community in the
      Eastern Province of Saudi Arabia (SA) to determine its point prevalence of
      neurological diseases. During this two-phase door-to-door study, all Saudi
      nationals living in Thugbah were first screened by trained interviewers using a
      pretested questionnaire (sensitivity 98%, specificity 89%) administered at a face
      to-face interview. Individuals with abnormal responses were then evaluated by a
      neurologist using specific guidelines and defined diagnostic criteria to document
      neurological disease. The questionnaire was readministered blind by a neurologist
      to all those with abnormal responses and a 1-in-20 random sample of those without
      abnormal responses, respectively. The family members of an individual with an
      abnormal response were also screened to improve accuracy. A total of 23,227
      Saudis (98% of the eligible subjects) were screened and those residing in Thugbah
      on the reference date (22,630) were used to calculate the point prevalence rates.
      Forty-two percent of those screened were in the first decade of life and only
      1.5% were more than 60 years old. There were marginally more females (50.2%) than
      males (49.8%). Consanguineous marriages especially between first cousins were
      present in 54.6%. The demographic characteristics of Thugbah community were
      similar to those in other parts of SA. The overall crude prevalence ratio (PR)
      for all forms of neurological disease was 131/1,000 population. All subsequent
      PRs are per 1,000 population. Headache syndromes were the most prevalent disorder
      (PR 20.7). The PR for all seizure disorders was 7.60, and the epilepsies (6.54)
      were more frequent than febrile convulsions (0.84). Mental retardation, cerebral
      palsy syndrome, and microcephaly were common pediatric problems with PRs of 6.27,
      5.30 and 1.99, respectively. Stroke, Parkinson's disease, and Alzheimer's disease
      were uncommon with respective PRs of 1.8, 0.27 and 0.22. Central nervous system
      (CNS) malformations (0.49) such as hydrocephalus and meningomyelocele were more
      prevalent than spinal muscular atrophy (0.13), congenital brachial palsy (0.13)
      and narcolepsy (0.04). Multiple sclerosis was rare (0.04). Osteoarthritis and low
      back pain syndromes were the main non-neurological conditions seen. The major
      medical diseases that may be neurologically relevant were diabetes mellitus,
      hypertension, and connective tissue disorders.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8272178
TI  - Epidemiology of migraine.
AB  - Migraine epidemiology presents methodological challenges, partially simplified by
      the use of the new International Headache Society (IHS) Classification. Most
      previously published migraine studies were clinic-based, which introduces bias
      since less than 5% of migraineurs consult specialists. A series of population
      based studies of migraine prevalence and incidence, based on the new operational
      IHS criteria, are now available and are reviewed, along with the migraine
      personality, comorbid psychiatric conditions and neuropsychological impairment.
      Migraine headaches are now divided into those with aura (classic migraine) and
      those without aura (common migraine). Headache occurs in about 91% of men and 96%
      of women, migraine occurs in about 6% of men and 18% of women (one-year
      prevalence). Migraine is most common in the third decade of life and in lower
      socioeconomic groups. It is associated with an increased prevalence of depression
      and panic attacks.

PMID- 8272179
TI  - Worldwide occurrence of Parkinson's disease: an updated review.
AB  - Comparison of Parkinson's disease (PD) prevalence and incidence in various parts
      of the world is difficult because methods of case ascertainment, diagnostic
      criteria, classification, medical facilities, and age distribution of the
      populations vary broadly in different studies. We minimized these differences by
      adjusting available data to a single standard population. Using this we
      calculated age-adjusted rates for 27 regional populations and analyzed PD
      frequency from 45 communities. We conclude: (1) with the exception of China,
      Japan and Africa, which have the lowest prevalence ratios, the actual prevalence
      variation for PD is probably lower than previously reported in geographically
      diverse populations; (2) geographic variation is unlikely to be due exclusively
      to racial factors, and (3) environmental risk factors for PD might differ
      regionally.

PMID- 8272180
TI  - A case-control study on the environmental risk factors of Parkinson's disease in
      Tianjin, China.
AB  - Using a case-control method, we studied the role of environmental risk factors
      and viral infection in the development of Parkinson's disease (PD) in China.
      Ninety-three PD patients and 186 controls were investigated with a questionnaire
      and from most of them, blood was taken to test the antibody levels of four virus
      (measles, rubella, HSV-1, CMV) IgG. The study result showed that positive family
      history, living near rubber plants, drinking river-water were associated with an
      increased risk of developing PD. In contrast, living in small cities, drinking
      well-water, drinking hard-liquor frequently, were associated with a decreased
      risk for PD. PD cases and controls did not differ with respect to other factors
      investigated including smoking and viral infection. These findings suggest that
      some environmental factors may be related to the development of PD, but further
      standardized studies will be required to confirm our results.

PMID- 8272181
TI  - Projected neurodegenerative disease mortality in the United States, 1990-2040.
AB  - Between 1990 and 2040, the United States elderly population is expected to grow
      from 31.6 to 68.1 million. In order to assess the implications of this increase
      on the mortality from neurodegenerative diseases in the United States, we used
      Census Bureau population estimates to formulate projections of the annual number
      of deaths from neurodegenerative diseases and from six comparison conditions
      (liver cirrhosis, colon cancer, lung cancer, cancer of the female breast,
      multiple sclerosis, and malignant melanoma), assuming that the United States
      disease-age-gender-race-specific death rates for 1985-1988 remain constant
      between 1990 and 2040. We find that neurodegenerative disease mortality increases
      by 119-231%, depending on the model of population growth used. For the 'middle'
      population growth model, the increase in annual neurodegenerative disease
      mortality is 166%. The major component of this increase is the rise in deaths
      attributed to dementia. For the six comparison diseases, the increases in
      mortality range from 52 (multiple sclerosis) to 130% (colon cancer). Given the
      current level of under ascertainment of neurodegenerative disease mortality and
      the conservative nature of the Census Bureau estimates of future population, it
      is likely that these projections are underestimates. The implications of these
      data are discussed.

PMID- 8272182
TI  - Adrenoleukodystrophy in France: an epidemiological study.
AB  - An epidemiological study was conducted in France to estimate the prevalence of
      adrenoleukodystrophy, a severe neurologic X-linked disorder affecting boys and
      young men. 129 cases were collected. Analysis of all cases born between 1956 and
      1986 with available clinical history allowed the calculation of the lowest
      estimation of the prevalence: 1 in 100,000 male births.

PMID- 8272183
TI  - Nutritional factors and multiple sclerosis in Gorski Kotar, Croatia.
AB  - An analysis was made of the possible influence of nutritional factors on the
      etiology of multiple sclerosis in Gorski Kotar (Croatia), a high-risk zone for
      this disease. A total of 46 MS patients and 92 controls, native-born residents of
      the area studied, participated in a case-control study. The questionnaire
      comprised 51 questions concerning dietary habits. An odds ratio (OR) estimate was
      obtained for all the factors which were more frequently found in the patients
      than in the controls. Large differences were found in the daily consumption of
      different quantities of full fat unskimmed milk (OR 21.7; chi 2 42.34; LL 7.12),
      potatoes with lard and fresh or smoked meat (OR 20.7; chi 2 15.52; LL 2.72), and
      new potatoes (OR 20.7; chi 2 15.52; LL 2.72). The consumption of unpasteurized
      milk, animal fat, smoked meat and potatoes are nutritional risk factors which
      could have an influence on the severity of primary demyelinization in a high-risk
      area for multiple sclerosis.

PMID- 8272184
TI  - The Lehigh Valley Recurrent Stroke Study: description of design and methods.
AB  - A community-based, prospective study was carried out in the Lehigh Valley to
      determine how 5 selected risk factors and their control affected the frequency of
      stroke recurrence and death after an initial stroke. The initial stroke was
      verified clinically and by computerized tomography. Between 1987 and 1989, 662
      patients with an initial stroke were enrolled and followed regularly every 4-6
      months for up to 7 visits. The average follow-up period was 2 years. The risk
      factors selected included hypertension, myocardial infarction, cardiac
      arrhythmia, diabetes mellitus and transient ischemic attacks. Interim death and
      its cause were noted. Surviving patients were interviewed and examined to
      determine whether a second stroke has occurred. At enrollment, 51.4% of the
      cohort was male. The average age of men was 69.6, while women were older,
      averaging 74.3 years. Stroke types were thrombosis, 14%; embolus, 23%; lacune,
      9%; nonspecific infarct, 48%, and intracerebral hemorrhage, 6%. There were 138
      deaths (21%) and 81 second strokes (12%) during follow-up. The frequency of risk
      factors at enrollment was as follows; hypertension, 59%; myocardial infarction,
      25%, cardiac arrhythmia, 47% (of which 16% had atrial fibrillation); diabetes
      mellitus, 29%, and transient ischemic attack, 18%. Of course many patients had
      multiple risk factors. We analyzed whether the presence of a risk factor at
      enrollment and its quality of control during follow-up affected stroke recurrence
      frequency and the mortality rates. These results will be reported in future
      papers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272185
TI  - A neural shift theory of migraine.
AB  - Migraine headache may lend itself to epidemiological inquiry that includes
      disruptive serotonergic psychosocial behaviors. To advance our knowledge of the
      etiology of this neurologic disorder, measurable psychosocial behaviors that are
      correlated with variability in monoamine neurotransmission need to be examined in
      the migraine population in a controlled fashion. It may be that those with
      migraine have a more difficult time adapting to internal or external
      environmental changes based on a different distribution of serotonin levels or
      activity. Psychosocial behaviors are outlined as possible serotonin indicator
      variables for future migraine investigation.

PMID- 8272186
TI  - The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in
      the dog.
AB  - Behavioral and pharmacological effects of oral administration of L-deprenyl in
      the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg
      while at higher doses there was stereotypical responding. There was evidence of
      improved cognitive function in animals chronically treated with a 1 mg/kg dose
      but the effectiveness varied considerably between subjects. Chronic
      administration produced a dose dependent inhibition in brain, kidney and liver
      monoamine oxidase B, and had no effect on monoamine oxidase A. There were also
      dose dependent increases in brain phenylethylamine and in plasma levels of
      amphetamine. Dog platelets did not have significant levels of MAO-B. Brain
      dopamine and serotonin metabolism were unaffected by L-deprenyl at doses up to 1
      mg/kg. It appears that for the dog, deamination of catecholamines is controlled
      by MAO-A. Nevertheless, it is suggested that L-deprenyl serves as a dopaminergic
      agonist, and there is also evidence that it affects adrenergic transmission.
      These catecholaminergic actions may account for the effects of L-deprenyl on
      behavior and cognitive function.

PMID- 8272187
TI  - Investigations into the biochemical basis of neuromodulation by 2
      phenylethylamine: effect on microtubule protein.
AB  - In order to understand the role of 2-phenylethylamine (PE) on neuronal responses,
      membrane changes have been studied using ESR probes. We report that the
      anticipated change in lipid membrane fluidity generally implicated in signal
      transduction has not been observed when PE is added to synaptosomes. As
      cytoskeletal architecture of presynaptic terminals appears to be involved in
      synaptic transmission, we non-specifically labeled synaptosomal membrane proteins
      with the sulfhydryl spin probe N-(2,2,6,6-tetramethyl-piperidine-1-oxyl-4-yl)
      maleimide (4-MAL-TEMPO). The addition of 2-phenylethylamine was found to induce
      conformational changes, in decreasing the ratio of weakly to strongly immobilized
      spin label (W/S) to 65% of the control. Of the membrane proteins labeled, 70-90%
      of the 4-MAL-TEMPO is covalently incorporated into cytoskeletal proteins. In
      isolated synaptosomes, incorporated with spin-labeled tubulin, the addition of PE
      reduced the W/S ratio to 51.6% of that obtained for polymerized microtubules. In
      vitro, PE reduced tau R of polymerized microtubules by 37%. We propose that the
      PE interaction with tubulin changes microtubule dynamics which may lead to its
      neuromodulatory action. The state of microtubular assembly can modulate the
      responsiveness of second messengers in the cell to the effect of stimulatory
      agents. The nature and physiological significance of PE interaction with tubulin
      is currently under investigation.

PMID- 8272188
TI  - Involvement of phospholipase A2 and arachidonic acid in the depolarization-evoked
      accumulation of Ca2+ in hippocampal mossy fiber nerve endings.
AB  - Depolarization-evoked increases in intraterminal free Ca2+ are required for the
      induction of neurotransmitter release from nerve terminals. Although the
      mechanisms that regulate the voltage-induced accumulation of presynaptic Ca2+
      remain obscure, there is evidence that the phospholipase-dependent accumulation
      of arachidonic acid, or its metabolites, may be involved. Therefore, fura-2
      loaded hippocampal mossy fiber nerve endings were used to investigate the
      relationships between membrane depolarization, lipid metabolism and presynaptic
      Ca2+ availability. It was observed that depolarization of the nerve terminals
      with KCl induced an increase in intraterminal free calcium that was inhibited
      more than 90% by a combination of voltage-sensitive Ca2+ channel blockers. In
      addition, the K(+)-dependent effects on Ca2+ concentrations were attenuated in
      the presence of phospholipase A2 inhibitors, but were mimicked by the
      phospholipase A2 activator melittin and exogenous arachidonic acid. Both the
      melittin- and arachidonic acid-induced increases in presynaptic Ca2+ were reduced
      by voltage-sensitive Ca2+ channel blockers. The stimulatory effects of
      arachidonic acid appeared to be independent of its further metabolism to
      prostaglandins. In fact, inhibition of either cyclooxygenase or lipoxygenase
      pathways resulted in a potentiation of the depolarization-evoked increase in
      intraterminal free Ca2+. From these results, we propose that some portion of the
      depolarization-evoked increase in intraterminal free calcium depends on the
      activation of phospholipase A2 and the subsequent accumulation of unesterified
      arachidonic acid.

PMID- 8272189
TI  - Characterization of the tyraminergic system in the central nervous system of the
      locust, Locusta migratoria migratoides.
AB  - Tyramine occurs in the central nervous system (CNS) of the migratory locust,
      Locusta migratoria migratoides. The distribution of tyramine within the CNS does
      not parallel that of octopamine. Tyramine is synthesised from tyrosine in the
      presence of tyrosine decarboxylase. A second decarboxylase in the CNS is active
      against 5HTP and DOPA. The locust ganglia incorporate tyramine by high- and low
      affinity uptake processes that appear to be independent of dopamine and
      octopamine. Depolarisation of the locust ganglia by high potassium concentration
      results in calcium-dependent release of incorporated [3H]tyramine.

PMID- 8272190
TI  - Postnatal development and GABA allosteric modulation of benzodiazepine receptor
      binding in the vitamin B-6 deficient rat brain.
AB  - We have measured the postnatal development and GABA modulation of benzodiazepine
      receptors in neuronal membranes from vitamin B-6 deficient and normal rats. In
      rats fed vitamin B-6 adequate and deficient diets there were age-dependent
      changes in [3H]flunitrazepam binding site affinity and in the number of binding
      sites. Vitamin B-6 deficiency produced a significant reduction in the potency of
      GABA to enhance [3H]flunitrazepam binding to cortical membranes prepared from 14
      day old rats. These results suggests an uncoupling of the GABAa/benzodiazepine
      receptor at a developmental period when the animals are most susceptible to
      spontaneous seizures.

PMID- 8272191
TI  - delta-Aminolevulinic acid effects on neuronal and glial tumor cell lines.
AB  - Acute intermittent porphyria (AIP) or precursor syndrome is a well described
      neuropathic clinical entity with incompletely known etiology. The most prominent
      biological abnormalities associated with this syndrome are elevations in serum
      and hepatic delta-aminolevulinic acid (ALA) and porphobilinogen (PBG). We
      determined the impact of ALA and PBG on human neuroblastoma and glioblastoma
      tumor cell survival as measured by the MTT assay. ALA proved to be cytotoxic in
      neuroblastoma cells, while PBG lacked cytotoxic effects. This cytotoxic effect of
      ALA could be enhanced by deferoxamine and diminished by heme, presumably through
      modulation of ALA synthesis. In conclusion, ALA excess may prove to be associated
      with the development of neuropathy in AIP.

PMID- 8272192
TI  - Endogenous methionine enkephalin may play an anticonvulsant role in the seizure
      susceptible El mouse.
AB  - After the intracisternal injection of three protease inhibitors which prevent the
      degradation of methionine enkephalin (amastatin, Des-Pro2-bradykinin, and
      phosphoramidon) and a mixture of these protease inhibitors, we investigated the
      effect on convulsive seizures in the seizure-susceptible El mouse. We also
      measured the cerebral methionine enkephalin content by high-performance liquid
      chromatography coupled with radioimmunoassay. Protease inhibitors significantly
      decreased both the incidence of seizures and the seizure score in El mice in a
      dose-dependent manner. This anticonvulsant effect was reversed by naloxone (2
      mg/kg, sc). The cerebral methionine enkephalin content increased significantly
      after the administration of protease inhibitors in comparison with saline
      injection. These findings suggest that it was not protease inhibitors but instead
      increase of endogenous methionine enkephalin that reduced the incidence of
      seizures and the seizure score in El mice. Together with our previous data, the
      present findings support our hypothesis that a deficit in anticonvulsant
      endogenous methionine enkephalin is involved in the pathogenesis of seizures in
      the El mouse.

PMID- 8272193
TI  - Regional differences in glutaminase activation by phosphate and calcium in rat
      brain: impairment in aged rats and implications for regional glutaminase
      isozymes.
AB  - Regional regulation of glutaminase by phosphate and calcium was examined in the
      temporal cortex (TCX), striatum (STR) and hippocampus (HIPP) from adult and aged
      male F344 rats. Phosphate-dependent glutaminase activity in adult rats was
      significantly lower (35-43%) in the HIPP (100 and 150 mM) and STR (150 mM)
      compared to PAG activity in the TCX. Phosphate activation in aged rats was 50-60%
      lower in the HIPP at concentrations greater than 25 mM compared to the aged TCX
      or STR. PAG activity in the TCX and STR was unaffected by age, but was
      significantly reduced (30-50%) in the HIPP from aged rats at phosphate
      concentrations of 25 mM and greater when compared to adult rats. In adult rats at
      concentrations of CaCl2 above 1 mM, PAG activity was significantly lower (60-75%)
      in the STR and HIPP when compared to the TCX. In aged rats, PAG activity (1 mM
      CaCl2) in the HIPP was significantly less (50%) than STR PAG activity in aged
      rats. Diminished PAG activity was seen only in the TCX (2.5 mM; 32%), and the
      HIPP (0.5 mM; 25% and 1 mM; 38%) at higher calcium concentrations compared to
      adult. Phosphate-independent calcium activation of PAG occurred in the HIPP but
      not in either the TCX or the STR. Addition of phosphate resulted in a synergistic
      activation of PAG in the STR and TCX, but not in the HIPP. These findings suggest
      that PAG is regionally regulated by phosphate and calcium, and this regulation is
      impaired in aged rats. These data also support the hypothesis that isozymes of
      PAG exist with different regulatory properties.

PMID- 8272194
TI  - Monoamine oxidase inhibition by L-deprenyl depends on both sex and route of
      administration in the rat.
AB  - The monoamine oxidase B (MAO-B) inhibitor L-deprenyl, widely used to treat
      Parkinson's disease, has frequently been studied in animal models. We have
      examined the effects of several variables on activity levels of MAO-A and B in
      rat brain and liver following chronic (3 wks) treatment with L-deprenyl.
      Significant effects were observed for sex (females showed lower overall MAO-B
      activity in the liver), dose (MAO-A and B inhibition increased with dose, with
      females exhibiting greater sensitivity), route of administration (subcutaneous
      injection was more efficient than oral dosing), and dosing interval (MAO-B was
      significantly inhibited when dosing interval was increased to as long as 168
      hours). Our results thus indicate that the effectiveness of L-deprenyl in vivo is
      dependent on several factors and that these must be taken into account in studies
      involving the benefits or risks of this drug.

PMID- 8272195
TI  - Hydrolysis of exogenous [3H]phosphatidylcholine by brain membranes and cytosol.
AB  - Phosphatidylcholine, in addition to the widely studied inositol phospholipids is
      cleaved to produce second messengers in neuronal signal transduction processes.
      Because of the difficulty in labelling and measuring the metabolism of endogenous
      phosphatidylcholine in brain tissue, we investigated the utility of measuring the
      hydrolysis of exogenous labelled substrate incubated with rat cerebral cortical
      cytosol and membrane fractions as has been successful in studies of
      phosphoinositide hydrolysis. In the cytosol [3H]phosphatidylcholine was
      hydrolyzed at a linear rate for 60 min of incubation and GTP gamma S stimulated
      hydrolysis by 63%. The products of phospholipase C and phospholipase D,
      phosphorylcholine and choline, contributed only 44% of the
      [3H]phosphatidylcholine hydrolytic products in the cytosol, with phospholipase D
      activity slightly predominating. GTP gamma S stimulated cytosolic phospholipase C
      and reduced phospholipase D activity. [3H]Phosphatidylcholine was hydrolyzed much
      more slowly by membranes than by cytosol. In membranes the production of
      [3H]phosphorylcholine and [3H]choline were approximately equal, contributing 27%
      of the total [3H]phosphatidylcholine hydrolysis, and GTP gamma S only caused a
      slight stimulation of phospholipase C activity. Chronic lithium treatment (4
      weeks) appeared to slightly reduce [3H]phosphatidylcholine metabolism in the
      cytosol and in membranes, but no statistically significant reductions were
      achieved. Cytosol and membrane fractions from postmortem human brain metabolized
      [3H]phosphatidylcholine slowly, and GTP gamma S had no effects. In summary,
      exogenous [3H]phosphatidylcholine was hydrolyzed by brain cytosol and membranes,
      and this was stimulated by GTP gamma S, but the complex contributions of multiple
      metabolic pathways complicates the application of this method for studying
      individual pathways, such as phospholipase D which contributes only a fraction of
      the total processes hydrolyzing exogenous [3H]phosphatidylcholine.

PMID- 8272196
TI  - The neuropeptide bradykinin stimulates phosphoinositide turnover in HSDM1C1
      cells: B2-antagonist-sensitive responses and receptor binding studies.
AB  - Bradykinin (BK) and its analogs (1 nM-100 microM) stimulated phosphoinositide
      (PI) turnover in murine fibrosarcoma (HSDM1C1) cells in a concentration-dependent
      manner. The relative potencies (EC50) were: BK = 48 +/- 4 nM; Lys-BK = 39 +/- 3
      nM; Met-Lys-BK = 158 +/- 33 nM, Des-Arg9-BK = 2617 +/- 598 nM (means +/- SEM, n =
      3-14). All these analogs were full agonists and they produced up to 5.4 +/- 0.4
      fold stimulation of PI turnover at the highest concentration (10-100 microM) of
      the peptides. In contrast, the analogs [D-Arg0-HYP3-Thienyl5,8-D-Phe7]-BK (HYP3
      antagonist), [D-Arg0-HYP3-Thienyl,5,8-D-Phe7]-BK (Thienyl antagonist) and Des
      Arg9-Leu8-BK were inactive, as agonists, at 0.1 nM-1 microM in this system. These
      data suggested that BK-induced PI turnover in these cells was mediated via B2
      type of BK receptors. This was confirmed further by the fact that both the B2
      selective Hyp3- and Thienyl-antagonists inhibited BK-induced PI turnover with KBS
      of 369 +/- 51 nM and 368 +/- 118 nM respectively while the B1-selective
      antagonist, Des-Arg9-Leu8-BK, was inactive at 1 microM. [3H]BK receptor binding
      studies revealed two binding sites, one with high affinity (Kd = 0.24 +/- 0.06
      nM; Bmax = 1.4 +/- 0.4 pmol/g tissue) and the other with low affinity (Kd = 18.5
      +/- 0.95 nM; Bmax = 25.1 +/- 0.52 pmol/g tissue), on HSDM1C1 cell homogenates.
      The rank order of affinity of BK analogs at inhibiting specific [3H]BK binding
      was similar to that found for PI turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272197
TI  - The potentiation of cortical neuron responses to noradrenaline by 2
      phenylethylamine is independent of endogenous noradrenaline.
AB  - 2-Phenylethylamine (PE) is an endogenous brain amine which produces
      sympathomimetic responses and potentiates cortical neuron responses to
      noradrenaline (NA). In order to examine further the mechanism of action of PE,
      extracellular recordings were made of the activity of single neurones in the
      cerebral cortex in urethane-anesthetized rats. Sympathomimetic responses to PE
      were blocked by pretreatment with reserpine, reserpine plus alpha-methyl-p
      tyrosine and desipramine. It is concluded that the sympathomimetic responses to
      PE are indirect. 2-Phenylethylamine potentiated cortical neuron responses to
      electrical stimulation of the locus coeruleus in a dose-dependent manner. This
      was seen when PE was given systemically (with as little as 1 microgram/kg) and
      iontophoretically. The effects of PE were not reproduced by its metabolite
      phenylacetic acid or its putative metabolite phenylethanolamine. Iontophoretic
      applications of PE (0-6 nA, 2-5 minutes) potentiated cortical neuron responses to
      iontophoretically applied NA, without affecting the spontaneous firing rate, or
      the responses to iontophoretically applied GABA or acetylcholine. This effect of
      PE was not blocked by pretreatment with alpha-methyl-p-tyrosine or desipramine,
      and was potentiated by pretreatment with reserpine and reserpine plus alpha
      methyl-p-tyrosine. It is probable that the ability of PE to modulate neuronal
      responses to NA does not involve the presynaptic NA terminal or endogenous NA and
      it is likely that PE acts directly to increase the efficacy of NA. These findings
      are consistent with the hypothesis that the physiological role of PE is to
      modulate catecholaminergic transmission within the central nervous system.

PMID- 8272198
TI  - Free radical scavenger depletion in post-ischemic reperfusion brain damage.
AB  - In the present study the influence of pretreatment with various GSH depletors
      such as buthionine sulfoximine (BSO) and diethylmaleate (DEM) was investigated in
      rats following cerebral post-ischemic reperfusion. Moreover, the effect of
      diethyldithiocarbamic acid (DDC), inhibitor of endogenous Cu,Zn-SOD, was
      evaluated. A significant depletion (40% of control value) of GSH levels was
      observed 24 h after DEM administration; after 48 h the value reached control
      levels. BSO showed maximal GSH depletion (59%) 24 h after administration and it
      was constant for almost 48 h. DDC administration caused a marked decrease (60%)
      of Cu,Zn-SOD activity 4 h after the injection and induced a marked decrease in
      percentage of survival with respect to control (untreated, ischemic) rats, when
      administered 4 h before ischemia. BSO and DEM prolonged the survival time of
      animals when administered 24 h before ischemia. This last paradoxical effect is
      unclear at present, but it might be due to an influence on glutamate cascade.

PMID- 8272199
TI  - Effects of pyridostigmine, corticotropin-releasing hormone and growth hormone
      releasing hormone on the pituitary-adrenal axis and on growth hormone secretion
      in dementia.
AB  - Alterations of neuroendocrinological indices determined by the impaired
      regulating effects of cholinergic neurotransmission have been described in
      primary dementia. In this study we have evaluated the effects of
      acetylcholinesterase inhibition by pyridostigmine on growth hormone (GH),
      adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses
      to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7
      patients with primary degenerative dementia and in 8 sex- and age-matched
      controls. Demented subjects showed higher cortisol basal levels and lower ACTH
      levels than controls. Pyridostigmine increased the GH response to GHRH in both
      groups, the effect being significantly enhanced in patients. An increase of ACTH
      and cortisol levels was found in both groups after pyridostigmine and CRH
      administration. Pyridostigmine pretreatment significantly increased the ACTH
      response to CRH in controls but not in patients. The obtained data may indicate
      that a muscarinic receptor upregulation and an impairment of somatostatinergic
      function are operative in the regulation of GH secretion in dementia. An
      underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the
      responses of ACTH and cortisol to CRH in this disorder.

PMID- 8272200
TI  - Cortisol responses of depressed children and adolescents to clonidine
      administration.
AB  - The responses of cortisol to acute administration of saline and of clonidine (2.5
      micrograms/kg B.W.) were examined in 10 children and adolescents with major
      depressive disorder and in 10 age- and sex-matched controls. Clonidine
      administration did not inhibit cortisol secretion in controls or in patients,
      contrary to what has been observed in depressed adults. In controls, but not in
      patients, clonidine administration induced a transitory increase of the steroid.

PMID- 8272201
TI  - Interferon-alpha as adjuvant treatment in chronic schizophrenia.
AB  - The therapeutic use of interferon (IFN)-alpha administered as adjuvant medication
      in chronic schizophrenia was investigated. Natural leukocyte IFN-alpha was given
      to 9 long-term hospitalized chronic schizophrenic patients daily as subcutaneous
      injection of 3 million units 5 times a week. The trial followed a placebo
      controlled double-blind crossover design. Each treatment period lasted for 8
      weeks with a 2-week washout period in between. IFN-alpha did not prove to be
      beneficial for the total group of patients. Yet, 3 patients improved during the
      IFN-alpha drug period. The clinical improvement was seen as better social
      competence and less affective tension in the ward surroundings.

PMID- 8272202
TI  - Diagnosis, the rate-limiting factor of biological depression research.
AB  - The third edition of the DSM provided a standardized, operationalized
      classification system of mood disorders. In this paper, the question is raised
      whether this system is a good starting point for biological depression research.
      The question is answered in the negative and the reasons why are being discussed.
      The proposed mood disorders are not properly validated and utterly heterogeneous
      and overlapping. An etiological axis is wanting and no hypothesis as to the
      relations between axis I and II diagnoses is required. The comorbidity problem is
      not satisfactorily resolved. The system leaves no room for a
      dimensional/functional analysis of mood and personality disorders. The frequent
      revisions that are only to a small extent based on preconceived research, lead to
      havoc in the research arena. The DSM III classification is considered to be the
      single most important factor hampering biological depression research. Ways to
      remedy the situation are pointed out.

PMID- 8272203
TI  - 123I-IMP SPECT brain imaging in epileptic psychosis: a study of two cases of
      temporal lobe epilepsy with schizophrenia-like syndrome.
AB  - To examine the relationship between functional abnormality of the brain and the
      development of epileptic psychosis, regional cerebral blood flow (rCBF) patterns
      with single photon emission computed tomography (SPECT) using N-isopropyl-(iodine
      123)-p-iodoamphetamine (123I-IMP) were serially examined in interictal stages
      with and without the psychotic state in 2 medicated patients with temporal lobe
      epilepsy with schizophrenia-like syndrome. Both patients had epileptic EEG foci
      in the left temporal lobe and schizophrenia-like syndrome in Bruens'
      classification of epileptic psychosis, mainly consisting of auditory
      hallucinations and delusions of persecution and reference accompanying the
      enhancement of interictal epileptic discharges. In both patients, the SPECT scans
      obtained in the stages without the psychotic state revealed focal hypoperfusion
      images in the left temporal lobe regionally consistent with the EEG foci. On the
      other hand, the SPECT scans in the stages with the psychotic states revealed
      focal hyperperfusion images in the left temporal lobe or amygdala in case 1, and
      a normal perfusion pattern without asymmetric images of the right and left
      temporal lobes in case 2. These results suggest that temporo-limbic dysfunction,
      in particular hyperfunction in the temporo-limbic system in the left dominant
      hemisphere, arises at the time of the psychotic state in epileptic psychosis.

PMID- 8272204
TI  - Single doses of piracetam affect 42-channel event-related potential microstate
      maps in a cognitive paradigm.
AB  - We examined whether a single administration of piracetam produces dose-dependent
      effects on brain functions in healthy young men. In 6 subjects, 42-channel event
      related EEG potential maps (ERP) were recorded during a task requiring subjects
      to watch single digits presented in a pseudorandom order on a screen and to press
      a button after all triplets of three consecutive odd or even digits. The ERP maps
      to the three digits of the correctly detected triplets were analyzed in terms of
      their mapped ERP field configuration (landscape). Different landscapes of the
      maps indicate different configuration of the activated neural population and
      therefore reflect different functional microstates of the brain. In order to
      identify these microstates, adaptive segmentation of the map series based on
      their landscapes was done. Nineteen time segments were found. These segments were
      tested for direct effects on brain function of three single doses of piracetam
      (2.9, 4.8 or 9.6 g) and a placebo given double-blind in balanced order. Piracetam
      mainly affected the map landscape of the time segments following the triplet's
      last digit. U-shaped dose-dependent effects were found; they were strongest after
      4.8 g piracetam. Since these particular ERP segments are recognized to be
      strongly correlated to cognitive functions, the present findings suggest that
      single medium doses of piracetam selectively activate differently located or
      oriented neurons during cognitive steps of information processing.

PMID- 8272205
TI  - New aspects in spinal diagnostics with 3-D computed tomography.
AB  - Three-dimensional imaging in computer tomography (3-D CT) has been rendered
      feasible by the development of special software programs. On the basis of the
      data from 50 spinal CTs, 3-D reformations are made. The method has proved
      effective especially in complicated vertebral fractures. There are regular
      correlations between the plane of the fracture and the choice of the axis of
      rotation as well as the nature of the reformations. A 3-D reformation is
      frequently more appropriate than a coronary or a sagittal 2-D reformation. In
      destructions of vertebrae due to tumors, the extent of bone destruction and the
      altered position of the vertebrae in relation to each other can be imaged. 3-D
      computer tomograms do not provide fundamentally new diagnostic information, but
      the understanding of pathological topography is improved.

PMID- 8272206
TI  - Function tests on the neuroendocrine hypothalamo-pituitary system following acute
      midbrain syndrome, with special reference to computertomographical and magnetic
      resonance imaging results.
AB  - Seventeen patients underwent a neuroendocrinological function test at a mean 6.3
      years following a severe craniocerebral trauma (CCT) accompanied by midbrain
      syndrome. An insulin hypoglycaemia test (IHT) and the combined pituitary anterior
      lobe test (CPALT) were applied. Whereas the IHT as maximum stimulator of the
      hypothalamo-pituitary system (HPS) showed an adequate reserve capacity, the CPALT
      yielded a partial limitation of the secretion dynamic in the somatotropic,
      adrenocorticotropic axis as well as a dysfunction in the FSH secretion.
      Neuroradiological tests could not establish substantial injury in the regio
      hypothalamica in any patient.

PMID- 8272207
TI  - Non-traumatic brain abscess.
AB  - Between 1953 and 1989 eighty cases of non-traumatic brain abscess were treated in
      our department. We have re-examined the clinical and neuroradiological features
      of this pathological process and present our therapeutic approach and results. We
      believe that the optimal treatment for brain abscess consists of surgical
      removal. The prognosis for these lesions has undergone a marked improvement over
      the last two decades in response to neuroradiological, microbiological and
      surgical advances. The most influential prognostic factor seems to be
      preoperative clinical status.

PMID- 8272208
TI  - Dorsal internal carotid artery aneurysm: classification, pathogenesis, and
      surgical considerations.
AB  - Despite the rarity of dorsal internal carotid artery (ICA) aneurysms they still
      offer surgical challenge to achieve a safe successful clipping due to their
      peculiar projection. In the past 13 years, 24 cases of dorsal ICA aneurysm were
      operated upon in our hospitals. Three separate groups of such aneurysms could be
      identified: group 1; where the aneurysms were located most proximally at the
      carotid-ophthalmic region, group 3; in which the aneurysms were present most
      distally just proximal to the ICA bifurcation, and group 2; where the aneurysms
      were located in between. All cases in this surgical series will be reviewed
      stressing upon the classification, pathogenesis, and surgical tactics of such a
      rare type of aneurysm.

PMID- 8272209
TI  - Advances in diagnosis and treatment of spinal hemangioblastomas.
AB  - Spinal hemangioblastoma usually leads to large intramedullary cysts. Until
      recently clinical and conventional radiological examination was often not able to
      detect single or multiple tumor niduses at the wall of a secondary syringomyelia
      cyst. Thus during surgical exploration the tumor not infrequently was missed,
      leading to misinterpretation of the pathological entity as syringomyelia, spinal
      gliosis or low grade spinal astrocytoma. This often resulted in explorative
      biopsy or decompressive laminectomy. Clinical deterioration postoperatively was
      not uncommon due to the remaining tumor and increasing spinal cord enlargement.
      Now magnetic resonance imaging allows the exact preoperative localization of the
      medullary lesion apart from the accompanying cysts and facilitates differential
      diagnosis of primary syringomyelia or other spinal cord neoplasms. Microsurgical
      techniques and laser-assisted resection have improved the outcome. We report on
      eight patients with spinal hemangioblastoma treated in our clinic since the
      installation of magnetic resonance imaging and laser-assisted microneurosurgery.

PMID- 8272210
TI  - Operative spondylodesis in injuries of the lower cervical spine.
AB  - In view of the high incidence of late instability during conservative treatment
      of cervical spine fractures, operative stabilization should be performed as soon
      as possible. Besides immediate decompression of the spinal cord, rapid
      mobilisation of the patient without external fixation is possible. We report on
      the results of operative treatment in 97 patients with injuries of the lower
      cervical spine. The indication for spondylodesis as well as the surgical methods
      and their complications are discussed.

PMID- 8272211
TI  - Germ cell tumor in the hypothalamo-neurohypophysial region: clinical features and
      treatment.
AB  - Twenty-one patients with germ cell tumors (17 germinomas and 4 teratomas)
      involving the hypothalamic-neurohypophysial (HN) region were reviewed
      retrospectively. Eleven patients were males and 10 females, and their ages ranged
      from 7 to 45 years (average 18.5 years). Diabetes insipidus was the initial and
      the most prominent symptom in most germinomas; in teratomas the most prominent
      symptom was visual disturbance. Fifteen patients with germinomas were treated by
      radiotherapy, and 4 with teratomas were treated by surgical resection alone. Two
      recent germinoma patients with extensive CSF dissemination were treated with
      systemic chemotherapy consisting of anticancer platinum drugs and etoposide,
      which resulted in a complete disappearance of the tumors. Patients with germinoma
      treated after the introduction of CT scanning had a greatly improved mortality
      rate, and their actual survival rate was 87.5% over 10 years. On the basis of
      this review, the authors consider that diagnosis at an early stage of the disease
      and chemotherapy, which can be an effective therapeutic alternative to radiation
      therapy, may improve not only the mortality rate but also the quality of life of
      patients with HN germ cell tumors.

PMID- 8272212
TI  - Melorheostosis--a very rare entity in neurosurgery.
AB  - Melorheostosis is of minor importance in neurosurgery. A case of this disease is
      reported, which required neurosurgical activity and the literature is reviewed.

PMID- 8272213
TI  - Two unusual complications of ventriculo-peritoneal shunts. Report of two cases.
AB  - Two cases in which thoracal extrusion and cervical disconnection complicated
      ventriculo-peritoneal shunts are reported. Other complications of distal shunts
      are also reviewed.

PMID- 8272214
TI  - Lethal septicemia caused by calcified cavo-tricuspid thrombus. Case report on a
      patient with atrial shunt.
AB  - With the introduction of one way calibrated shunt systems, made of silicon
      rubber, an efficient treatment of hydrocephalus seemed to be possible. The
      mortality rate decreased rapidly for example for non-communicating hydrocephalus
      from 80 to 20%. However, other complications appeared, such as shunt infections,
      shunt malfunctions and even severe thromboembolic complications and septic shock.
      This report presents one patient with shunt-treated normal pressure hydrocephalus
      who developed pulmonary emboli, mural calcified atrial thrombus with involvement
      of the tricuspid valve and shunt infection with lethal septic shock. Despite of
      an aggressive treatment, he died of multiple organ system failure.

PMID- 8272215
TI  - Choroid plexus arteriovenous malformation (AVM) in a newborn. Case report.
AB  - We report here on an unusual case of AVM with intraventricular hemorrhage in a
      full-term newborn infant. Clinical and radiological findings are discussed in the
      light of the recent literature.

PMID- 8272216
TI  - Glomerular tip lesion in the 1962-66 Medical Research Council trial of prednisone
      in the nephrotic syndrome.
AB  - A multi-centre controlled trial of prednisone in the nephrotic syndrome in adults
      was run by the Medical Research Council between 1962 and 1966. Sections of renal
      biopsies and necropsy kidneys from the trial had been kept. These were restained
      25 years later with periodic acid-methenamine silver and examined for the
      glomerular tip lesion, an abnormality of the kidney described after the trial in
      patients with the nephrotic syndrome. The glomerular tip lesion was found in
      material from 10 patients, representing 7% of 150 patients with the nephrotic
      syndrome and glomerulonephritis. In the trial, seven had been classified as
      minimal-change nephropathy and three as proliferative glomerulonephritis.
      Detailed follow-up was limited but it was known that two patients died shortly
      after presentation, not, apparently, from progression of the glomerular disorder;
      that none of the others had progressed to renal failure, at least for the
      duration of follow-up of the trial, 2-4 years; and that those classified as
      minimal-change nephropathy appeared to have behaved clinically as though they had
      minimal-change nephropathy. These findings show that at least one adult series of
      minimal-change nephropathy has contained cases of the glomerular tip lesion but
      that clinically this may not be an important error as the conditions behave
      similarly. A more important error may be to call the glomerular tip lesion a
      proliferative glomerulonephritis, which may lead the clinician to withhold
      steroids.

PMID- 8272217
TI  - Effect of captopril on renal extraction of renin, angiotensin II, atrial
      natriuretic peptide and vasopressin, and renal vein renin ratio in patients with
      arterial hypertension and unilateral renal artery disease.
AB  - Plasma renin activity (PRA) and plasma concentrations of angiotensin II (AngII),
      atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were determined
      in the abdominal aorta and the renal veins before and 1 h after peroral ingestion
      of captopril 25 mg in 29 patients with arterial hypertension and unilateral renal
      artery stenosis or occlusion, in order to study the effect of ACE inhibition on
      single-kidney extraction ratio (ER) of PRA, AngII, ANP, and AVP, and on renal
      vein renin ratio (RVRR). PRA was increased, AngII and ANP were reduced, and AVP
      unchanged after captopril. On the affected side the negative ER or PRA (-1.03)
      and AngII (-0.28) and the positive ER of ANP (0.25) and AVP (0.14) were not
      significantly changed by captopril. On the non-affected side ER of AngII and ER
      of ANP were significantly reduced (ER of AngII, 0.41-0.00, ER of ANP, 0.29-0.17),
      but ER of PRA and ER of AVP were unchanged. RVRR was not significantly changed by
      captopril. RVRR was greater than 1.5 in 79% of the patients before captopril, in
      82% after captopril, and in 93% either before or after captopril. It is concluded
      that captopril reduces ER of AngII and ER of ANP on the non-affected side but not
      on the affected side in unilateral renal artery disease with hypertension, and
      that the use of RVRR both before and after captopril improves the predictive
      value of RVRR with regard to the diagnosis of unilateral renal artery disease.

PMID- 8272218
TI  - Modulation of abnormalities in renal haemodynamics and vasoactive mediators by
      nifedipine in patients with psoriasis on low-dose cyclosporin.
AB  - Ten patients with psoriasis received a 3-month course of cyclosporin (2.5
      mg/kg/day) followed by a 3-month washout period, before commencing a 3-month
      course of cyclosporin and nifedipine SR 20 mg b.d. Serial haemodynamic and
      biochemical measurements were performed before, during, and after treatment.
      Total renal blood flow (RBF) was measured following an intravenous injection of
      [99mTc]-DTPA based on a renographic analysis of the first-pass effect in the
      kidneys, and GFR was estimated from the subsequent clearance of this radiotracer.
      A significant individual change in RBF or GFR was taken as 25% and 20%
      respectively. Simultaneous assays of the circulating vasoactive mediators renin,
      aldosterone, angiotensin II, and atrial natriuretic peptide were performed. Two
      patients withdrew from the study because they could not tolerate nifedipine,
      leaving eight for complete analysis. The significant reductions in RBF and GFR
      which occurred on cyclosporin alone (P < 0.05; ANOVA) did not occur with added
      nifedipine. Four months after this second course, RBF and GFR had recovered. The
      response to nifedipine was, however, variable and unpredictable. Of the four
      patients to show a significant decline in GFR on cyclosporin alone, only two
      showed a significant improvement on the combined therapy. Of the six patients who
      showed a significant decline in RBF on cyclosporin alone, only four showed
      benefit from the added nifedipine. Nifedipine suppresses the increase in blood
      pressure which occurred on cyclosporin alone. The circulating concentration of
      angiotensin II was significantly less on cyclosporin and nifedipine than on
      cyclosporin alone (P < 0.05; Student's t test).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272219
TI  - Acute renal failure in patients with acute pancreatitis: prevalence, risk
      factors, and outcome.
AB  - A total of 267 consecutive patients presenting with acute pancreatitis were
      studied retrospectively. We analysed the collected data to determine the
      prevalence of acute renal failure (ARF), and factors significantly predisposing
      to its occurrence and outcome. The prevalence of ARF in our patients was 16%.
      Only 2% had isolated ARF. Seventy-three percent of patients with additional organ
      system failure suffered ARF after the onset of other organ failure. The number of
      organ system failure was significantly greater before, compared to after, the
      development of ARF. Using multiple logistic regression we found that pre-existing
      chronic disease and cardiovascular and haematological failure were independent
      risk factors positively related to the development of ARF, whereas systemic
      infection was not. Overall mortality from ARF was 81%. Chronic disease, local
      complications and the presence of additional organ system failure and their
      number significantly increased mortality in ARF patients. No patients requiring
      renal replacement therapy survived. ARF is a common complication of severe acute
      pancreatitis, but occurs late in the disease course, and mostly preceded by other
      organ system failure. The prognosis of patients with ARF is extremely poor,
      indicating that more emphasis should be placed on prevention of ARF.

PMID- 8272220
TI  - Effectiveness of low-dose erythropoietin in predialysis chronic renal failure
      patients.
AB  - Recombinant human erythropoietin (rHuEpo) has been shown to be both effective and
      usually safe in patients with chronic renal failure who have not yet reached the
      stage requiring dialysis. There are, however, disturbing reports on the
      possibility of deterioration of the reserve renal function in association with
      rHuEpo therapy. Most of the published studies have used rHuEpo in doses of 50-150
      U/kg three times weekly subcutaneously. An open-label trial of rHuEpo therapy was
      conducted on 21 patients with chronic renal failure treated sequentially at a
      referral hospital, rHuEpo was used in doses of 50 U/kg twice weekly for 4 weeks
      followed by 25 U/kg twice weekly for 8 weeks subcutaneously, a regimen
      substantially lower than current recommendations. This was associated with a
      gentle but significant increase in haematocrit (P < 0.05) and haemoglobin (P <
      0.05), while the serum creatinine and the reciprocal of the creatinine remained
      stable, with a tendency to improve rather than worsen (P = 0.06). We conclude
      that there is no need to aim at a rapid increase in haematocrit and haemoglobin
      by rHuEpo therapy; rather a gentle increase using modest doses is both effective
      and safe.

PMID- 8272221
TI  - Late referral to maintenance dialysis: detrimental consequences.
AB  - Thirty per cent of patients who started maintenance haemodialysis at our
      institution between January 1989 and December 1991 had been referred at a very
      late stage of their renal disease. To assess the causes and consequences of such
      late referral we retrospectively compared clinical and laboratory features of 65
      patients who had been referred less than 1 month prior to first dialysis (late
      referral, or LR group) and of 153 patients who had been previously followed-up by
      us for more than 6 months (early referral, or ER group). Age, sex ratio, and
      socioeconomic status were similar in the two groups. In the LR group, 38 patients
      had never been referred to a nephrology unit, whereas 27 had discontinued
      nephrological surveillance. Fluid overload, severe hypertension, and/or pulmonary
      oedema was present in 57% of LR versus 15% of ER patients (P < 0.001). Mean (+/-
      1 SD) systolic and diastolic blood pressure was greater in the LR than the ER
      group (173 +/- 19/99 +/- 12 versus 147 +/- 15/84 +/- 8 mmHg, P < 0.001). Mean
      plasma concentration of creatinine, urea and phosphate was significantly greater,
      whereas bicarbonate, calcium, haematocrit and albumin were less in the LR than
      the ER group. Most (88%) LR patients started dialysis in emergency conditions
      through central vein catheterization. Total hospital stay lasted 34.5 +/- 16.3
      days in LR versus 5.8 +/- 3.0 days in ER patients (P < 0.0001), resulting in an
      excess cost of 0.2 million French francs per LR patient.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8272222
TI  - Subjective global assessment of nutrition in dialysis patients.
AB  - Malnutrition is a major negative prognostic factor in dialysis patients. Simple
      and reliable estimations of nutritional status may therefore prove of particular
      value in the follow-up of these patients. To validate subjective global
      assessment (SGA) in dialysis patients we compared subjective global assessment
      with objective measurements (anthropometry, bioelectrical impedance, biochemical
      measurements) in 59 chronic uraemic patients treated by haemodialysis (n = 36) or
      CAPD (n = 23). Subjective global assessment was performed by an observer unaware
      of the results of objective measurements and was related to serum albumin (r = 
      0.51, P < 0.001) and bioelectric impedance phase angle (r = -0.58, P < 0.001) as
      well as with MAMC (r = -0.28 P = 0.028), %fat (r = -0.27, P = 0.042) and nPCR (r
      = -0.29 P = 0.027). Multiple regression analysis showed that the relationship of
      subjective global assessment (as a dependent variable) with objective
      measurements (covariates) was stronger (multiple r = 0.77) than the relationship
      found with univariate analysis. This finding indicates that subjective global
      assessment gives a well-based and balanced estimation of nutritional status. Our
      data show that subjective global assessment is a clinically adequate method for
      assessing nutritional status in dialysis patients. Being an inexpensive method of
      well-proven reliability, subjective global assessment can be recommended for a
      more frequent assessment of nutritional status in dialysis patients.

PMID- 8272223
TI  - Serum lipoprotein(a) concentration in patients with chronic renal failure
      receiving haemodialysis: influence of apolipoprotein (a) genetic polymorphism.
AB  - Serum lipoprotein(a) (Lp(a)) was measured in 101 men with end-stage chronic renal
      failure (CRF) receiving haemodialysis and in 101 age-matched male controls.
      Apolipoprotein(a) genetic polymorphism was determined by immunoblotting in 100
      patients and in 92 controls. Patients with CRF on haemodialysis had significantly
      greater serum Lp(a) than controls. Apolipoprotein(a) phenotype frequencies in
      patients with CRF did not differ from those of the control group. Both patients
      and controls with phenotype S2 had greater serum Lp(a) than those with phenotype
      S4. It should be emphasized that serum Lp(a) was significantly greater in
      patients on haemodialysis than controls, both for those with phenotype S2 and
      those with S4. Increased serum Lp(a) together with other lipoprotein
      abnormalities in patients with CRF on haemodialysis imply an increased
      cardiovascular risk. Genetic polymorphism clearly influences serum Lp(a) both in
      controls and patients. In the latter group CRF itself, dialysis, or both, also
      play a role in increasing Lp(a).

PMID- 8272224
TI  - Ultrasonographic detection of thickened joint capsules and tendons as marker of
      dialysis-related amyloidosis: a cross-sectional and longitudinal study.
AB  - Dialysis-related amyloidosis is characterized by a beta 2-microglobulin (beta 2M)
      infiltration of joint synovia, tendons and capsules. We report a cross-sectional
      ultrasonographic evaluation of supraspinatus tendon and femoral neck capsule
      thickness in 49 patients on long-term haemodialysis. Ultrasonographic evaluation
      was repeated 21 +/- 4 (SD) months later in 16 patients. Normal values for the
      supraspinatus tendon and femoral neck capsule were defined in a group of control
      subjects without history or signs of joint disease. Among the 49 patients, aged
      21-86 (median 59) years, dialysed for 1-228 (median 97) months, 33 had at least
      one abnormal joint. The prevalence of patients with at least one and at least two
      abnormal joints, the number of abnormal joints per patient, and the thickness of
      the supraspinatus tendon and femoral neck capsule increased significantly with
      dialysis duration (P < 0.001 for all parameters considered). By multiple linear
      regression analysis, mean thickness of the supraspinatus tendon was positively
      related to both dialysis duration (P < 0.0001) and age (P = 0.036) independently.
      All (n = 11) patients with radiological and/or histological evidence of dialysis
      related amyloidosis at the time of ultrasonography had thickened supraspinatus
      tendon and/or femoral neck capsule; which were also thickened in an additional 22
      patients without radiological evidence of dialysis-related amyloidosis. Three
      died within 5-10 months of the ultrasonographic investigation: post-mortem
      examination of the periarticular tissue confirmed that the detected thickening
      was due in all three to beta 2M amyloid infiltration.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8272225
TI  - Results of endoscopic management of carpal-tunnel syndrome in long-term
      haemodialysis versus idiopathic patients.
AB  - The purpose of this paper is to compare the results of our endoscopic management
      of carpal-tunnel syndrome caused by long-term haemodialysis to that with no
      apparent cause (idiopathic). We have operated on 551 hands in 370 patients using
      the Universal Subcutaneous Endoscope system under local anaesthesia without a
      pneumatic tourniquet on an out-patient basis since 1986. Ninety-six hands in 64
      patients who suffered from carpal-tunnel syndrome from long-term haemodialysis
      and 85 hands in 52 patients who suffered from carpal-tunnel syndrome for no
      apparent cause were statistically analysed using complete pre- and postoperative
      electrophysiological and clinical studies for periods of time ranging from over 6
      months to 4.8 years (mean 16.9 months). Electrophysiological and clinical results
      showed that our endoscopic management in long-term haemodialysis patients is
      effective, safe and yields the same results as in patients who suffered from
      carpal-tunnel syndrome for no apparent cause.

PMID- 8272226
TI  - Anti-hepatitis C virus antibodies and hepatitis C virus viraemia in haemodialysis
      patients.
AB  - Sera from 82 haemodialysis patients were tested for anti-HCV, HCV-RNA, and HBsAg.
      Alanine aminotransferase (ALT) activity was monitored weekly for 2 months. Anti
      HCV was positive in 31 patients (37.8%), showing different single-peptide
      patterns. HCV-RNA was detected in 26 anti-HCV-positive patients (84%) and also in
      two of 21 anti-HCV-negative patients. Twenty-seven (87%) of the 31 anti-HCV
      positive patients had persistently normal ALT values; 22 of these patients were
      HCV-RNA positive. The four patients with elevated ALT values had HCV viraemia.
      HBsAg was positive in nine anti-HCV-negative patients. The close correlation
      between HCV viraemia and HCV status, independently of ALT values, requires that
      anti-HCV dialysis patients must be considered potentially infective and dialysed
      with reserved machines and/or in separate shifts.

PMID- 8272227
TI  - Evoked potentials (VEPs and BAEPs) in a large cohort of short- and long-term
      haemodialysed patients.
AB  - To evaluate the presence and the severity of uraemic encephalopathy (UE) in
      regular dialysis treatment patients in relation to dialytic age, pattern reversal
      visual evoked potentials (PRVEPs) and brainstem auditory evoked potentials
      (BAEPs) were respectively performed in 86 and 98 patients on haemodialysis for 1
      194 months, divided into three subgroups according to dialytic age (group 1, < 5
      years of regular dialysis; group 2, 5-10 years; group 3, > 10 years). VEPs in the
      whole group of 86 patients and in each subgroup with different dialytic age
      differed significantly from controls for both eyes, 41.7% of whom had
      pathological P100; no differences were observed between the three subgroups.
      BAEPs were pathological in 9.7% of the ears and 18.4% of patients. On the right
      ear the three subgroups were significantly different from controls in the
      latencies of peaks III and V; subgroup 2 and 3 differed from controls in the I-V
      interpeak, while the interpeak I-III was different from controls only in subgroup
      3. On the left ear the three subgroups differed significantly from controls in
      the latencies of peak V; subgroup 2 and 3 were significantly different from
      controls in the latency of peak I; subgroup 3 was different in the peak III
      latency; subgroup 1 and 3 were different from controls in the interpeak I-V; no
      differences were observed in BAEPs between the three subgroups with increasing
      dialytic age. No significant correlations were found between the
      neurophysiological parameters and some biochemical parameters (urea, creatinine,
      PTH).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272228
TI  - Skin surface pH, moisture, and pruritus in haemodialysis patients.
AB  - Pruritus is one of the most common complaints of haemodialysed patients. However,
      its pathogenesis remains unclear. Dryness of the skin and the effects of pH
      changes on the nerve endings in the skin have been suggested as related factors.
      In the present study we measured skin pH using a skin pH meter and skin moisture
      using a corneometer at four different sites in 41 haemodialysis patients, before
      and after dialysis, and in 40 healthy controls. Thirty patients (73%) complained
      of pruritus, six severe constant, 12 moderate and 12 mild. Skin surface pH was
      higher in patients than in controls in the upper back (5.54 +/- 0.14 versus 5.22
      +/- 0.08, P < 0.02), forearm (5.5 +/- 0.1 versus 5.13 +/- 0.1, P < 0.01) and
      forehead (5.35 +/- 0.08 versus 5.04 +/- 0.07, P < 0.004), whereas there was no
      difference in the axilla. Haemodialysis had no effect on skin pH, and there was
      no correlation with blood pH, blood bicarbonate and serum electrolytes. There was
      no correlation between skin surface pH and pruritus. Skin moisture was lower in
      haemodialysis patients than in controls in the forehead and axilla. There was no
      correlation with pruritus. Skin surface pH is higher in haemodialysed patients
      than in healthy controls in most areas of the body, despite the fact that these
      patients have a decreased blood pH. Thus, the skin pH is not related to systemic
      acid-base balance. It is possible that the uraemic state affects the ability of
      the dermal cells to secrete acid, making the skin more susceptible to bacterial
      and fungal infections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272229
TI  - Removal of limulus reactivity and cytokine-inducing capacity from bicarbonate
      dialysis fluids by ultrafiltration.
AB  - Bicarbonate-based dialysate solutions support the rapid growth of bacteria. The
      long-term (360-h) efficacy of ultrafiltration by two polysulphone ultrafilters in
      removing not only endotoxin but also the cytokine(IL-1, TNF)-inducing capacity
      was evaluated using an experimental circuit contaminated with Pseudomonas
      aeruginosa filtrates. One of the polysulphone ultrafilters was submitted to a
      standard sanitization procedure every 12 h (hypochlorite 1.2% solution for 5 min
      and rinsing for 20 min). Endotoxin was detected by the kinetic quantitative
      chromogenic limulus amoebocyte lysate (LAL) assay. Immunoreactive IL-1 and TNF
      were evaluated in the lysates of peripheral blood mononuclear cells containing 5
      x 10(5) human monocytes. The results of the present studies show that although
      LAL-reactive bacterial products were significantly removed in post-ultrafilter
      samples, they remained detectable, albeit below the upper limit accepted by the
      present European pharmacopeias (< 0.125 EU/ml). The removal of cytokine-inducing
      capacity was time-dependent and correlated with time of use in the case of the
      sanitized ultrafilter. Beyond the time of use, two other factors emerged as
      possibly capable of reducing the efficacy of the ultrafilter in removing LAL
      reactive bacterial components, namely the pressure and the cytokine-inducing
      activity in pre-ultrafilter samples. Preincubation with polymyxin B, an agent
      that irreversibly binds lipid A and blocks lipid A-induced biological activities,
      did not abrogate the cytokine-inducing capacity in all post-ultrafilter samples;
      this suggests that either low-molecular-weight endotoxin subunits or lipid A
      unrelated components may be responsible for the residual biological activity in
      post-ultrafilter samples.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272230
TI  - Prevention of blood loss in dialysers with DEAE-cellulose membranes does not
      require increased doses of heparin.
AB  - Binding of heparin to DEAE-cellulose membranes may reduce bioavailable heparin,
      thus increasing the amount of heparin needed for anticoagulation during dialysis.
      To test this hypothesis, blood loss and coagulation were evaluated during
      dialysis with DEAE-cellulose and polysulphone membranes. The heparin dose
      required to effect a given increase in the baseline recalcified activated
      clotting time (RACT) was determined using a pharmacokinetic model. Blood
      remaining in the dialyser post-dialysis (RBV) was measured by red cell lysis and
      haemoglobinometry. Plasma thrombin-antithrombin III complex (TAT) was used to
      assess activation of the coagulation system. RBV and changes in TAT were
      determined in two crossover studies. Firstly, DEAE-cellulose membranes were used
      at doses of heparin calculated to increase baseline RACT by 12.5% and 25%.
      Secondly, DEAE-cellulose and polysulphone membranes were compared at a heparin
      dose calculated to increase baseline RACT by 15%. RBV for DEAE-cellulose
      membranes was independent of the dose of heparin and did not differ from that
      found for polysulphone membranes. TAT concentrations increased during dialysis;
      however, there was no difference between the two membranes. These results show
      that DEAE-cellulose membranes do not require increased heparin to avoid dialyser
      associated blood loss.

PMID- 8272231
TI  - Effect of prior bilateral nephrectomy on haemoglobin and blood pressure outcome
      after transplantation.
AB  - Changes in blood pressure and haemoglobin concentration before and after renal
      transplantation were compared in 15 patients with renal failure due to chronic
      pyelonephritis who had undergone pretransplant bilateral nephrectomy and 15
      control patients whose primary renal disease was chronic pyelonephritis and who
      were matched for age, sex and graft function but had not undergone nephrectomy.
      Bilateral nephrectomy resulted in a significant worsening of anaemia prior to
      transplantation and a decline in blood pressure. However, by 6 and 12 months
      after renal transplantation both haemoglobin and blood pressure were similar in
      nephrectomized and non-nephrectomized patients and in the normal range. We
      conclude that in patients with renal failure due to chronic pyelonephritis,
      pretransplant nephrectomy has no major impact on long-term blood pressure and
      haemoglobin levels achieved after successful renal transplantation.

PMID- 8272232
TI  - Effects of zinc supplementation in chronic haemodialysis patients.

PMID- 8272233
TI  - Ambulatory blood pressure monitoring assessment of blood pressure control in
      hypertension associated with chronic renal failure.

PMID- 8272234
TI  - Phaeochromocytoma in a long-term haemodialysis patient; diagnosis and management.

PMID- 8272235
TI  - Massive bladder haemorrhage after thrombolytic therapy in a haemodialysis patient
      with secondary amyloidosis.

PMID- 8272236
TI  - Light-chain nephropathy and anti-neutrophil cytoplasmic antibody associated
      vasculitis.

PMID- 8272237
TI  - Again on HCV prevalence and the different types of testing sera.

PMID- 8272238
TI  - Long-term follow-up after vitamin D3 poisoning in childhood.

PMID- 8272239
TI  - Outcome in acute renal failure.

PMID- 8272240
TI  - Sulfadiazine-induced obstructive renal failure in a patient with acquired
      immunodeficiency syndrome (AIDS)

PMID- 8272241
TI  - Correction of a metabolic alkalosis induced by lemon consumption by acetate-free
      biofiltration.

PMID- 8272242
TI  - Cytomegalovirus colitis in a patient with recent failure of kidney transplant.

PMID- 8272243
TI  - Progression of occlusive renal vascular disease and axillofemoral bypass grafts.

PMID- 8272244
TI  - Increase of plasma and red blood cell vitamin E concentration in uraemic patients
      on maintenance haemodialysis undergoing treatment with recombinant
      erythropoietin.

PMID- 8272245
TI  - 'Tumour' in the ascending colon in a patient with recurrent bacterial
      peritonitis.

PMID- 8272246
TI  - Behaviour of platelets and beta-thromboglobulin.
AB  - Platelet count, platelet aggregation responses, and plasma beta-thromboglobulin
      were assessed before and at intervals during each study dialysis. As expected,
      modest thrombocytopenia was observed following treatment with all dialysers, but
      Filtral showed the least effect. Concordantly, modest increases in plasma beta
      thromboglobulin were observed with all devices except Filtral (caveat: the device
      also seems to adsorb beta-thromboglobulin). Interpatient variability was more
      striking for platelet aggregation responses, and made it difficult to discern
      patterns; however, aggregation in response to ADP was augmented during
      haemodialysis with the Filtral device, and blunted when the G120 M was employed.
      Differences between hollow-fibre and parallel plate devices with the same
      membrane material suggest that membrane geometry, manufacturing residues,
      membrane support, or potting materials may also contribute to platelet
      activation.

PMID- 8272247
TI  - Introduction, demography, and general methods.
AB  - The International Cooperative Biocompatibility Study was planned to analyse the
      symptomatic and laboratory response to seven different dialysers studied in five
      centres in four countries. The dialysers used were the G10-3N, G120 M, CD 4000, T
      150, Duo-Flux, F 60, and Filtral (see below for full description). A total of 37
      patients in the Veterans Administration Lakeside Medical Center, Chicago; Henry
      Ford Hospital, Detroit; Osaka City University Hospital, Osaka; Wilhelm Pieck
      University Hospital, Rostock; and Huddinge University Hospital, Stockholm were
      studied. All patients had been dialysed for a minimum of 6 months, were non
      diabetic, stable, and compliant; and most were middle-aged and male. Patients
      were treated three times per week for 2 weeks with each new dialyser with random
      assignment to one of four orders of dialyser use. The same manufacturing lot of
      each dialyser, blood line sets and needles were used by all centres. Delivery
      systems were volumetric controlled except for some patients in Osaka treated with
      negative-pressure equipment. Individual patient prescriptions (Kt/Vs for urea),
      in use prior to the study, were continued. Kt/Vs for all treatments were derived
      from reported blood flows and blood water corrected mass transfer coefficients
      multiplied by dialyser surface area. Clinical data were measure pre-, intra- and
      postdialysis. Hourly signs, symptoms, drugs, and nursing interventions were
      recorded using the identical treatment record at all centres. In addition,
      patients completed a questionnaire form (translated into the appropriate
      language) at least weekly, relating symptoms experienced with each dialyser.
      Laboratory investigations were performed during the sixth consecutive
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272248
TI  - beta 2-Microglobulin and granulocyte elastase.
AB  - Plasma beta 2-M was measured by radioimmunoassay in samples obtained before and
      after dialysis with seven different dialysers, tested according to the protocol
      of the International Cooperative Biocompatibility Study (ICBS). Plasma beta 2-M
      was corrected for contraction of its distribution volume, which was assumed to be
      equal to the extracellular fluid volume. The uncorrected plasma beta 2-M
      concentration increased with all conventional dialysers, including the G10-3N,
      (cuprammonium cellulose plate), G120 M (cuprammonium cellulose hollow fibre), CD
      4000 (cellulose acetate) and T 150 (polymethylmethacrylate). However, no
      significant differences were found between the predialysis and the corrected
      postdialysis plasma beta 2-M concentrations with these conventional dialysers,
      and thus no evidence of net generation or release of beta 2-M was found in this
      study. With high-permeability membranes, the corrected postdialysis beta 2-M
      values were decreased by 27.1% with the Duo-Flux Artificial Kidney, 53.5% with F
      60, and 34.6% with Filtral, indicating that dialysers with these membranes
      eliminate plasma beta 2-M to a certain extent. The complex of granulocyte
      elastase with alpha 1-antiproteinase in plasma was also measured in samples from
      the arterial blood line collected before, and after 30 and 120 min of dialysis
      with each of the seven dialysers in this study. All dialysers elicited an
      increase in the mean plasma elastase concentrations which was more than twice as
      high with cuprammonium cellulose plate than with all of the others. The change of
      elastase at 120 min of dialysis varied considerably with each dialyser and was
      statistically significant with all except CD 4000, F 60, and Filtral.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8272249
TI  - Dialysis-induced hypoxaemia.
AB  - A crossover study to compare the effects of seven different dialysers on blood
      gas conditions during dialysis using acetate-containing dialysate was carried out
      at five centres in four countries. A significant decrease in pO2 was noted at
      both 15 and 60 min after the start of dialysis for all dialysers, with the
      greatest decrease at 60 min. Filtral caused the greatest reduction and F 60 the
      least change at both 15 and 60 min. These differences were statistically
      significant according to the ANOVA multiple-range test for variance. pCO2 also
      declined by 1.0-2.7 mmHg at 15 min and by 0.7-3.8 mmHg at 60 min. The delta pCO2
      was comparable across dialysers and no significant differences were found.
      Although pH showed no change at 15 min, it was slightly but significantly
      increased at 60 min across all dialysers compared to predialysis values. There
      were no statistical differences between dialysers. Calculated blood bicarbonate
      content significantly decreased at 15 min and recovered at 60 min. Along with the
      greater decrease in pO2, a larger loss of total CO2 was noted for Filtral. On the
      other hand F 60 caused the least change in total CO2. This difference may be due
      to membrane characteristics affecting the diffusion coefficient for O2, CO2, and
      bicarbonate. Multifactorial mechanisms are likely to be involved, but reflex
      hypoventilation and an increase in O2 consumption also contributed to hypoxaemia
      in this study.

PMID- 8272251
TI  - Biocompatibility: the need for a systems approach.

PMID- 8272250
TI  - Relationship between dialyser type and signs and symptoms.
AB  - A crossover study to compare the effects of seven different dialysers on
      intradialytic symptoms in 37 patients during dialysis with acetate-containing
      dialysate was performed at five centres in four countries. The same manufacturing
      lot of each dialyser and of blood line sets were used by all centres. The same
      clinical data (duration of dialysis, blood pressure, weights, temperature, drugs,
      symptoms, and treatments) and technical data (blood flow, dialyser clearance, and
      ultrafiltration rate) were collected. Kt/V for urea was used to determine
      dialysis prescribed. Intradialytic symptoms and signs were measured hourly or
      when observed by staff using the haemodialysis treatment form (see Introduction).
      After each week of treatment with a particular dialyser, patients completed a
      questionnaire relating to the presence and severity of symptoms. (Only presence
      or absence of symptoms are presented.) Wide differences in dialysis duration and
      blood flow between centres were noted. These may have contributed to the
      differences between centres in relationship to staff reported responses to
      different dialyser: Dialysers with the lowest incidence of both signs and
      symptoms and of chest pain, back pain, and itching (arbitrarily designated
      bioincompatibility symptoms) were the Duo-Flux and Filtral, with the G120 M, the
      CD 4000, and the T 150 having the highest incidence. By patient questionnaire the
      most biocompatible dialysers were the T 150, F 60, and the Filtral, with the most
      symptom producing being the G120 M and the G10-3N. Perceptions of symptoms
      between patients and staff differed substantially overall and between centres.
      Hypersensitivity reactions were noted in two patients, both occurring with
      cuprammonium cellulose hollow-fibre dialysis, despite adherence to manufacturers'
      instructions concerning saline priming and removal. Both patients showed antibody
      titres greater than 1:160 against ethylene oxide-HSA. Ethylene oxide was not
      detected (limit of detection 1 part per million) in dialysers, blood line sets,
      or fistula needles. The study suggests that dialysis symptom reporting is
      complicated by individual perceptions, staff reactions, and the efficiency of
      recording. In this study ethnic and cultural differences must be added to the
      haemodynamic differences and other prescription-related elements in influencing
      symptoms. Despite these problems a hierarchy of dialyser-related symptoms and
      signs could be discerned which largely paralleled laboratory findings of
      biocompatibility. Future comparative studies relating symptomatology to membrane
      and dialyser structure should consider the variables identified as influencing
      symptoms and their reporting.

PMID- 8272252
TI  - Behaviour of white blood cells and the complement system.
AB  - Seven different types of dialysers were investigated in five dialysis centres in
      four countries with respect to behaviour of white blood cells and the complement
      system. The results of this controlled crossover study demonstrated significant
      differences in the dialysers. Those containing cuprammonium cellulose (G10-3N and
      G120 M) showed the greatest changes in white blood cell count, including
      monocytes and neutrophils, as well as the greatest complement activation. With
      regard to lymphocytes the subpopulation of low-mobility cells, which were
      predominantly the B-cells, showed the greatest mobility with dialysers containing
      cuprammonium cellulose. The PAN copolymer- and PMMA-containing dialysers Filtral
      and T 150 clearly caused the least changes in white blood cells and complement
      factors. Dialysers containing cellulose acetate and polysulphone membranes (Duo
      Flux Artificial Kidney, CD 4000, and F 60) produced only a moderate decrease of
      WBC, monocyte, neutrophil, and lymphocyte counts, and this result corresponded to
      a relatively small change in complement factors.

PMID- 8272253
TI  - Enhancement of the N-methyl-D-aspartate response in spinal dorsal horn neurons by
      cAMP-dependent protein kinase.
AB  - Glutamate-gated ion channels mediate excitatory synaptic transmission in the
      central nervous system and are involved in synaptic plasticity, neuronal
      development and excitotoxicity (5,24). These ionotropic glutamate receptors were
      classified according to their preferred agonists as AMPA (alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid), KA (kainate), and NMDA (N-methyl-D-aspartate)
      receptors [Trends Pharmacol. Sci., 11 (1990) 25-33]. The present study of NMDA
      receptor channels expressed in acutely isolated spinal dorsal horn (DH) neurons
      of young rat reveals that they are subject to modulation through the adenylate
      cyclase cascade. Whole-cell voltage-clamp recording mode was used to examine the
      effect of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase (PKA) on
      the responses of DH neurons to NMDA. Whole-cell current response to NMDA was
      enhanced by 8 Br-cAMP, a membrane permeant analog of cAMP or by intracellular
      application of cAMP or catalytic subunit of PKA.

PMID- 8272254
TI  - n-6 polyunsaturated fatty acids increase the neurite length of PC12 cells and
      embryonic chick motoneurons.
AB  - We have tested the action of three n-6 polyunsaturated fatty acids, either free
      or in the form of ethyl esters, on the neurite outgrowth in two neuronal models:
      a rat pheochromocytoma cell line (PC12) and embryonic chick motoneurons, after 7
      days in culture. An inverted microscope coupled with the 'VIDS 4' software was
      used for measuring the neurite length. Free fatty acids were found to be
      cytotoxic at 10(-3) M and the maximal increase of the neurite length was obtained
      at 10(-5) M. In contrast, fatty acids in the form of ethylesters were not
      cytotoxic and at 10(-3) M induced the maximal increase in the neurite length.
      This increase (1.2 to 2 fold) significantly differed from the control and was
      dose-dependent. These results were discussed in relation to the action of fatty
      acids on enzyme activation and membrane fluidity.

PMID- 8272256
TI  - Firing pattern and location of respiratory neurons in cat medullary raphe nuclei.
AB  - Extracellular spikes of single respiratory neurons were explored in the medullary
      raphe nuclei in spontaneously breathing decerebrated or Nembutal-anesthetized
      cats. A total of 26 respiratory neurons, whose spikes were confirmed to originate
      from the cell bodies, was recorded in the raphe obscurus and pallidus. They could
      be classified into six types based on the relation of their firing to the phases
      of respiration: (1) inspiratory (I) decrementing (I-DEC, n = 14), (2) I-frequency
      modulated (n = 3), (3) I-augmenting (I-AUG, n = 2), (4) late I (n = 2), (5)
      expiratory (E) augmenting (E-AUG, n = 3) and (6) I-E phase-spanning (I-E PS, n =
      2). These results suggest the existence of neurons relating to the control of
      respiration in the medullary raphe nuclei.

PMID- 8272255
TI  - A subpopulation of mouse striatal cholinergic neurons show monoamine oxidase
      activity.
AB  - We examined the histochemical localization of monoamine oxidase (MAO) in the
      mouse striatum. MAO activity was observed in glial cells and vessels in
      accordance with previous reports in the rat brain. In addition to these
      previously documented structures, we found MAO-containing neurons in the mouse
      striatum. Enzyme inhibition experiments showed that MAO in the positive neurons
      was predominantly of type B. Double-labeling studies showed that in this region
      these neurons were cholinergic. The functional role of MAO activity in the mouse
      striatal cholinergic neurons is presently unclear.

PMID- 8272257
TI  - Post-synaptic activity evoked in the rostral ventrolateral medullary neurones by
      stimulation of the defence areas of hypothalamus and midbrain in the rat.
AB  - Neurones in the rostral ventrolateral medulla (RVLM) of the rat were recorded
      intracellularly (n = 30) and extracellularly (n = 91) in vivo. 91% of them had
      spontaneous activity with frequencies of 1.1-29.9 Hz. Onset latencies of the
      excitation induced by the stimulation of the hypothalamic and midbrain defence
      areas ranged from 1.5 to 44 ms and 2 to 60 ms respectively. There was no
      statistical difference between two groups. Excitation followed by inhibition or
      inhibition followed by excitation was observed in these processes. Excitatory
      post-synaptic potentials (EPSPs) were summated by simultaneous stimulation of
      both sites and the onset latency was changed with the change of stimulus
      intensity. It is concluded that projections from the defence areas of
      hypothalamus and midbrain are relayed to RVLM neurones forming excitatory and
      inhibitory synapses; one mechanism of the effect summation caused by both sites
      is via EPSPs.

PMID- 8272259
TI  - Selectively high expression of the transcription factor AP1 in telencephalic
      structures of epileptic E1 mice.
AB  - In ddY mouse brain, the transcription factors AP1 and CREB were rich in the
      cerebral cortex, hippocampus and cerebellum but relatively poor in the striatum,
      hypothalamus and midbrain. In contrast, the transcription factor Myc was rather
      poorly distributed in mouse brain under the conditions employed. Among these 3
      transcription factors examined, DNA binding activities of only AP1 were
      invariably higher in telencephalic structures, such as the cortex, hippocampus
      and striatum, of the epileptic El mice than in those of parent ddY mice. These
      results suggest that the transcription factor AP1 may be at least in part
      responsible for molecular mechanisms underlying pathogenesis of a variety of
      abnormal symptoms observed in epileptic El mice.

PMID- 8272258
TI  - Evidence that each nerve varicosity on the surface of the mouse vas deferens
      secretes ATP.
AB  - The secretion of ATP from visualised varicosities on the surface of the mouse vas
      deferens was determined. Small diameter microelectrodes (about 6 microns and 20
      microns) were placed over a set of 2 to 5 varicosities visualised with DiOC2(5)
      in order to record excitatory junctional currents (e.j.c.s') arising from the
      evoked secretion of quanta. In high external calcium concentrations, [Ca2+]o, the
      amplitude-frequency distribution of e.j.c.s' was well described by binomial
      statistics in which binomial parameter n and the number of varicosities were
      approximately the same. Idazoxan (1 microM) had no effect on the e.j.c.s' or the
      binomial parameters p and n. Suramin (100 microM) blocked the e.j.c.s' as well as
      the spontaneous e.j.c.s' (s.e.j.c.s') in all cases, reducing n and p to zero.
      These results indicate that all varicosities secrete the transmitter blocked by
      suramin, presumably ATP.

PMID- 8272260
TI  - Neurocalcin immunoreactivity in rat olfactory bulb.
AB  - Neurocalcin, a newly discovered calcium-binding protein belonging to the
      recoverin-like superfamily, was detected immunohistochemically in tufted cells
      from the rat olfactory bulb. More precisely, only periglomerular tufted cells and
      some tufted cells from the external plexiform layer were expressing neurocalcin.
      Western blot analysis has confirmed the presence of neurocalcin in rat olfactory
      bulb. Lack of neurocalcin immunoreactivity in mitral cells and periglomerular
      cells favor a different phylogenic origin between tufted and mitral or
      periglomerular cells.

PMID- 8272261
TI  - Somatic currents contribute to frequency-dependent spike-broadening in supraoptic
      neuroendocrine cells.
AB  - Voltage-gated K and Ca currents were recorded in acutely dissociated
      neuroendocrine cells of the supraoptic nucleus. The effect of repeated activation
      of the currents by trains of (10) voltage pulses over a range of pulse-repetition
      frequencies were examined. There was a significant reduction of K-current
      amplitude and a significant increase of Ca-current amplitude during trains with
      high repetition frequencies. Frequency-dependent changes in K and Ca conductances
      may contribute to frequency-dependent spike-broadening which is exhibited during
      bursts of action potentials generated by these neurons.

PMID- 8272262
TI  - GM-1 ganglioside administration combined with physical therapy restores
      ambulation in humans with chronic spinal cord injury.
AB  - In a randomized double-blind cross-over study, humans with chronic spinal cord
      injury received ganglioside GM-1 or placebo for 2 months. GM-1, administered
      intravenously at a dose of 100 mg, 6 days a week, resulted in a statistically
      significant improvement of motor scores (P < 0.05), whether administered before
      or after 2 months of placebo. There was no placebo effect on motor scores.
      Subjects who received GM-1 before placebo maintained their improvement during the
      placebo phase. Subjects who received GM-1 ambulated with a reciprocal gait, using
      orthotics, for longer distances and at a faster rate whether the drug was
      administered before or after placebo. These results constitute the first finding
      that any chemical substance improves locomotion in human chronic spinal cord
      injury.

PMID- 8272263
TI  - The presence of corticotropin-releasing factor-like immunoreactive synaptic
      vesicles in axon terminals with nicotinic acetylcholine receptor-like
      immunoreactivity in the median eminence of the rat.
AB  - Whether or not corticotropin-releasing factor (CRF) containing synaptic vesicles
      are located in axon terminals with nicotinic acetylcholine receptor (nAChR) in
      the median eminence (ME) of the rat was examined by electron microscopic double
      labeling immunocytochemistry combining the pre-embedding avidin-biotin-peroxidase
      complex (ABC) method for nAChR with the post-embedding immunogold staining method
      for CRF. nAChR-like immunoreactivity (nAChR-LI) was found in the cell membranes
      of the axon terminals in the ME. CRF-like immunoreactivity (CRF-LI) was found in
      dense granular vesicles (about 100 nm in diameter) in the axon terminals. Double
      labeling method revealed that some of nAChR-LI axon terminals were found to
      contain CRF-LI dense granular vesicles. The results indicate that nicotine may
      act on nAChR in axon terminals to release CRF.

PMID- 8272264
TI  - A subgroup of bipolar cells in human retina is GABA-immunoreactive.
AB  - The distribution of GABA in the perifoveal and the near and far peripheral region
      of human retina was studied with peroxidase anti-peroxidase immunocytochemistry
      applied on semithin epoxy resin sections. Among the labeled amacrine cells in
      these regions, four types can be identified: putative diffuse A2 amacrines,
      stratified semilunar amacrines, interstitial amacrines and small displaced
      amacrines. GABA-immunoreactive interplexiform cells and ganglion cells also
      occur. Contrary to previous post-embedding studies, our preparations show that
      some bipolar cells in the near and far peripheral region are GABA-immunopositive.
      This indicates that a number of bipolar cells in human retina does have an
      enhanced GABA content.

PMID- 8272265
TI  - Phospholipid metabolite levels are altered in cerebral cortex of patients with
      dominantly inherited olivopontocerebellar atrophy.
AB  - We measured metabolic precursors and breakdown products of phosphatidylcholine
      (choline, glycerophosphocholine (GPC) and phosphatidylethanolamine (ethanolamine,
      glycerophosphoethanolamine (GPE)) as well as the amino acid serine, a precursor
      of phosphatidylserine, in four morphologically unaffected cerebral cortical areas
      obtained at autopsy from 14 patients with dominantly inherited
      olivopontocerebellar atrophy (OPCA) and 13 controls matched for age and
      postmortem interval. As compared with the controls, mean GPE levels were elevated
      by 49-57% in frontal and parietal cortices of OPCA brains whereas concentrations
      of ethanolamine were significantly reduced in temporal, occipital and parietal
      cortex (-40 to -54%). This resulted in increased GPE/ethanolamine ratios (+80 to
      +146%). GPC levels were significantly increased (by 53%) in the frontal cortex of
      OPCA patients relative to controls. Free serine levels were reduced by 20 to 28%
      in frontal, parietal, temporal, and occipital cortices. These abnormalities in
      phospholipid metabolite levels in OPCA resemble those seen in Alzheimer's
      disease, although the changes in GPC are less pronounced. These changes in
      phospholipid metabolism in OPCA cerebral cortex, a brain area spared from
      neurodegenerative changes, points to generalized disturbances in cellular
      membrane function in this disease.

PMID- 8272266
TI  - Formalin-induced pain antagonizes the development of opiate dependence in the
      rat.
AB  - Clinical studies have suggested that patients who take morphine for pain relief
      do not show a high degree of dependence. The present study examined the
      development of naloxone-precipitated withdrawal in rats receiving morphine in the
      presence or absence of formalin-induced pain. Morphine (10 mg/kg, i.p.) or saline
      was administered for 4 consecutive days 10 min after a subcutaneous injection of
      50 microliters of 2.5% formalin or saline into the hind-paw. On the 5th day, rats
      were injected with naloxone (1 mg/kg, i.p.) and observed for signs of
      precipitated withdrawal (ptosis, teeth chattering and excretion/diarrhea).
      Naloxone-precipitated withdrawal symptoms were significantly greater in rats that
      received morphine in the absence of pain than in rats that received morphine in
      the presence of pain.

PMID- 8272268
TI  - The effect of long-term treatment with antidepressant drugs on the hippocampal
      mineralocorticoid and glucocorticoid receptors in rats.
AB  - The effects of long-term (28 days) and short-term (2 days) administration of
      imipramine or amitriptyline (10 mg/kg p.o., twice daily) on the density (Bmax)
      and affinity (Kd) of mineralocorticoid (MR) and glucocorticoid receptors (GR)
      were determined in the rat hippocampus. MR and GR were examined by an in vitro
      [3H]corticosterone binding to soluble molecules in the cytosol, using the
      selective GR agonist RU 28362 to discriminate between MR and GR. Long-term
      treatment with antidepressant drugs significantly increased the Bmax of GR (by 22
      45%; both 2 and 72 h after their last dose), but did not modify the Bmax of MR
      and the Kd of GR and MR. The above data suggest that up-regulation of GR may be
      involved in the effect of antidepressant drugs on the activity of the
      hypothalamic-pituitary-adrenal axis.

PMID- 8272267
TI  - Potentiating interactions between medullary serotonin and thyrotropin-releasing
      hormone-induced gastric erosions in rats.
AB  - The central interaction between 5-HT and exogenous and endogenous thyrotropin
      releasing hormone (TRH)-induced gastric lesions was investigated in conscious
      rats. Intracisternal injection (i.c.) of the TRH analog, RX 77368, (2.5 nmol) in
      indomethacin (2 mg/kg, i.p.)-treated rats produced 1.4 +/- 0.1% of gastric corpus
      mucosal lesions which were aggravated by 30 and 208% by simultaneous i.c.
      injection 5-HT at 10 and 100 nmol, respectively, whereas i.v. 5-HT (100 nmol) had
      no effect. The 5-HT2/1c antagonist, ketanserin, given i.c. at 10 or 100 nmol
      reduced by 44 and 76%, respectively, cold restraint stress-induced 3.4 +/- 0.6%
      gastric lesions in indomethacin-pretreated rats whereas, when given i.v. (100
      nmol), it was inactive. Ketanserin or 5-HT (100 nmol, i.c.) alone did not modify
      the gastric mucosa. The present data suggest a potentiating interaction between
      endogenous 5-HT and TRH which has implication in the understanding of medullary
      mechanisms involved in gastric lesion formation induced by cold restraint.

PMID- 8272269
TI  - Uridine diphosphate-glucuronosyltransferase activities in rat brain microsomes.
AB  - The glucuronidation capacity of rat brain microsomes was investigated using a
      series of chemically related phenolic compounds and fatty acids which are usually
      glucuronidated in vivo. Most of the phenols assayed were glucuronidated, but no
      glucuronide formation was detected for stearic and alpha-linolenic acids, 4
      methylphenol, bilirubin, morphine, dopamine and serotonin. The activity of
      uridine diphosphate-glucuronosyltransferase (UGT) towards 1-naphthol represented
      0.28% of that obtained with liver microsomes. The inhibitory effects on the
      formation of 1-naphthol glucuronide of some endogenous and exogenous substances
      were investigated. The results suggest that only the isoform of UGT conjugating 1
      naphthol is present in rat brain.

PMID- 8272270
TI  - Electrical coupling between primary hair cells in the statocyst of the squid,
      Alloteuthis subulata.
AB  - Intracellular recordings were made from primary sensory hair cells located on the
      dorsal side of the anterior crista segment of the squid statocyst. These hair
      cells were electrophysiologically identified by the occurrence of an antidromic
      action potential after electrical stimulation of the crista nerve. Two types of
      subthreshold, depolarising potentials were observed in the primary sensory hair
      cells. Firstly, those due to efferent inputs onto the primary hair cells and
      secondly those correlated one-to-one with action potentials in neighbouring
      primary hair cells. The former depolarising potentials could be blocked by bath
      applied cobalt, indicating chemical transmission, while the latter could not.
      Injection of a depolarising or hyperpolarising current into a primary hair cell
      depolarised or hyperpolarised, respectively, a neighbouring primary hair cell
      implying that the hair cells are electrically coupled with an electrical coupling
      coefficient of up to 0.4.

PMID- 8272271
TI  - A new subdivision of the rat midbrain periaqueductal gray based on its
      myeloarchitecture.
AB  - A new subdivision of the periaqueductal gray (PAG) based on its myelin content is
      described. Using a methacrylate-resin embedding technique for high resolution
      light microscopy, a myeloarchitectonic map of the normal rat PAG was made. Six
      main columns were distinguished. Column I is the central thin subependymal layer,
      in which myelinated axons are virtually absent. This layer is surrounded by
      column II with many rostrocaudally oriented fibers. Lateral and dorsolateral to
      column II lies column III, which contains rostrocaudally as well as tangentially
      oriented fibers. Column III is divided into a ventral and a dorsal part by column
      IV. This column is located in the dorsolateral part of the PAG and contains very
      few, mostly tangentially oriented fibers. Column V is located ventrally and
      contains a mixture of rostrocaudally and tangentially oriented fibers. Column VI
      is only present in the most caudal part of the PAG and contains mainly tangential
      fibers.

PMID- 8272272
TI  - Nicotine dependence: intervention strategies for the physician.
AB  - Nicotine dependence is the most common serious medical problem in primary care.
      Its complications are common and far reaching, both for the person addicted to
      tobacco and for other people in the environment. Nicotine dependence is highly
      treatable.

PMID- 8272273
TI  - Tobacco control in New Jersey: a public forum on smoking and youth.
AB  - The New Jersey State Commission on Smoking OR Health held a public forum on
      tobacco control. The public provided a strong mandate for action, and
      recommendations to the Commission were made concerning smoking, youth, and
      environmental tobacco smoke.

PMID- 8272274
TI  - Medicolegal aspects of treating drug and alcohol addiction.
AB  - The authors present an overview of different areas of interface between medicine
      and the law, applicable to the treatment of patients with drug and alcohol
      problems. The five case reports are a sample of the medicolegal issues that can
      arise in the treatment of drug addicts and alcoholics.

PMID- 8272275
TI  - Addiction and the law: confidentiality to disclosure.
AB  - With growing demands for access to medical records, confidentiality and privacy
      will increasingly compete with professional desire for collaboration and the need
      for reimbursement. Physicians need to be aware of medicolegal safeguards.

PMID- 8272276
TI  - Adolescent substance abuse prevention.
AB  - Increasing attention is being focused on the prevention of substance use, rather
      than treatment. The author critiques the literature and provides a conceptual
      framework for a better understanding of adolescent substance abuse prevention
      under school-based, psychosocial, and legislative models.

PMID- 8272277
TI  - Methadone maintenance treatment: dispelling myths and recovering truths.
AB  - Methadone maintenance treatment has allowed for stabilization and normalization
      in the lives of hundreds of thousands of chronic opiate addicts. This article
      reviews methadone treatment and dispels some myths and recovers some truths about
      this treatment.

PMID- 8272278
TI  - The crisis of addictive gambling in New Jersey.
AB  - Compulsive gambling is a problem that affects not only individuals and families,
      but also the community. All classes of people and sexes can be touched by this
      disease. The health community must become more aware, and make early referral for
      treatment.

PMID- 8272279
TI  - Behavioral approaches to the treatment of addiction.

PMID- 8272280
TI  - Addiction: the treatment of dual diagnosis.
AB  - Dual diagnosis is used when two disorders occur simultaneously in one person. The
      two disorders can refer to two medical illnesses, a psychiatric illness and a
      medical or surgical illness, or two psychiatric illnesses. The cost of
      misdiagnosis of dual disorders is high.

PMID- 8272281
TI  - Addiction disorders of New Jersey physicians.
AB  - The principles of treatment for addictive disorders are simple: Identify the
      disorder. Find skilled therapists to direct a treatment plan. Pursue the plan.
      Develop the skills to cope with life after addiction. Seek appropriate support
      from family and systems in the community.

PMID- 8272282
TI  - Fever: causes and consequences.
AB  - The present review distinguishes pathogenic, neurogenic, and psychogenic fever,
      but focuses largely on pathogenic fever, the hallmark of infectious disease. The
      data presented show that a complex cascade of events underlies pathogenic fever,
      which in broad outline - and with frank disregard of contradictory data - can be
      described as follows. An invading microorganism releases endotoxin that
      stimulates macrophages to synthesize a variety of pyrogenic compounds called
      cytokines. Carried in blood, these cytokines reach the perivascular spaces of the
      organum vasculosum laminae terminalis (OVLT) and other regions near the brain
      where they promote the synthesis and release of prostaglandin (PGE2). This
      prostaglandin then penetrates the blood-brain barrier to evoke the autonomic and
      behavioral responses characteristic of fever. But then once expressed, fever does
      not continue unchecked; endogenous antipyretics likely act on the septum to limit
      the rise in body temperature. The present review also examines fever-resistance
      in neonates, the blunting of fever in the aged, and the behaviorally induced rise
      in body temperature following infection in ectotherms. And finally it takes up
      the question of whether fever enhances immune responsiveness, and through such
      enhancement contributes to host survival.

PMID- 8272283
TI  - Tourette syndrome: associated symptoms and most disabling features.
AB  - Four hundred forty-six patients with Tourette Syndrome (TS) and/or their parents
      completed a 52-item self-report survey about vocal and motor tics, and the
      frequency of associated co-morbid conditions of aggression, obsessions and
      compulsions, attentional problems, sleep disturbance, mood disturbance, anxiety,
      and self-mutilative behaviours which have been frequently reported in the
      literature on TS. Respondents also responded to an open-ended question regarding
      the most disabling aspects of TS. Results were analyzed within two age groups;
      under 18 years of age (N = 245) and 18 years of age or older (N = 177). Tics and
      associated conditions were the most frequently reported disabling aspect by both
      age groups. Subjects under age 18, however, reported significantly more frequent
      problems with hyperactivity, temper control, aggressive behaviours and
      sleepwalking than adults with TS.

PMID- 8272284
TI  - Evidence for and against the Naples high- and low-excitability rats as genetic
      model to study hippocampal functions.
AB  - The Naples high- (NHE) and low-excitability (NLE) are two rat lines, selectively
      bred for high and low activity levels in a Lat-maze, respectively. Because the
      activity level in a novel environment depends mainly on the integrity of the
      hippocampal formation, and NLE and NHE rats differ with a similar background of
      emotionality, arterial blood pressure, and learning ability, they have been
      proposed as animal model to study hippocampal functions. Our aim is to prove
      evidence in favor and against this hypothesis. The evidence in favor indicates
      that NLE/NHE rats have a defective spatial processing, and pertains to (a)
      Differential activity in a spatial novelty situation (selection trait),
      proportional to the stimulus complexity rats are exposed to (NHE are hyper- and
      NLE-rats hypoactive); and (b) Impaired working memory in a six-arm non-reinforced
      tunnel maze in both lines compared to random-bred rats, that was reversed by the
      introduction of a reinforcer. In addition, multiple evidence of (i) lower intra-
      + infrapyramidal mossy fiber terminals in both NLE/NHE vs. controls; (ii)
      increased sensitivity of hippocampal elements to microinjections of vasopressin
      (but not oxytocin) and of "delta" (but not "mu") opioids; (iii) lower number of
      high-affinity glucocorticoid receptors; (iv) lower number of alpha- but not beta
      adrenergic receptors in the hippocampus and hypothalamus of NHE rats only; and
      (v) the genotype-dependent behavior of a DNA fraction with fast turnover, suggest
      that both NHE/NLE are "disintegrated" at the hippocampal interface. Further,
      neurobehavioral covariations among individual differences reveal nonlinear,
      complex relationships, an evidence apparently against the hypothesis.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8272285
TI  - Sweeteners: state of knowledge review.
AB  - Sweeteners are widely used in the food and pharmaceutical industry. The purpose
      of this paper is to review our current knowledge of sweet taste from chemical,
      biochemical, electrophysiological, psychophysical, and psychological points of
      view. The most common sweetners likely to be used in food and pharmaceuticals
      will be examined in detail. First, the chemical structures of sweet compounds
      including saccharides, diterpene glycosides, polyols, amino acids, dipeptides,
      and other nonsugars will be discussed. Second, biochemical approaches to
      understanding sweetner receptors will be reviewed. Third, electrophysiological
      and behavioral approaches to understanding sweetner receptors will be discussed.
      Fourth, psychophysical studies in humans will be shown to be consistent with
      biochemical and neurophysiological data. In addition, the basic mechanisms of
      sweet taste revealed by psychophysical studies will be given, including the role
      of multiple receptor sites, hydrogen bonding, and sodium transport. Finally, the
      factors that affect preference for sweet taste including the psychological and
      physiological variables associated with sweet preference will be explored.

PMID- 8272286
TI  - The significance of the metabolism of the neurohormone melatonin: antioxidative
      protection and formation of bioactive substances.
AB  - Recent findings suggest that the ability of melatonin to enter all body tissues
      and to be metabolized, enzymatically or nonenzymatically, in any of them results
      in a spectrum of effects, which exceed substantially those transduced by membrane
      receptors. These actions comprise the formation of various bioactive compounds
      such as N-acetylserotonin, 5-methoxytryptamine, N,N-dimethyl-5-methoxytryptamine,
      5-methoxytryptophol, cyclic 2-hydroxymelatonin, pinoline, and 5-methoxylated
      kynuramines. Apart from enzymatic metabolism, nonenzymatic reactions with free
      radicals, in particular the superoxide anion and the hydroxyl radical, represent
      a new and significant aspect of melatonin's biological role. Melatonin represents
      the most potent physiological scavenger of hydroxyl radicals found to date, and
      recent findings suggest an essential role of this indoleamine for protection from
      hydroxyl radical-induced carcinogenesis and neurodegeneration.

PMID- 8272287
TI  - Caring: a privilege and our responsibility.

PMID- 8272288
TI  - Does use of permanent suture material affect outcome of the modified Pereyra
      procedure?
AB  - OBJECTIVE: To determine the effect of absorbable versus permanent suture on
      outcome of the modified Pereyra procedure for stress urinary incontinence.
      METHODS: A review was performed of case-series reports of outcome of the modified
      Pereyra procedure for stress urinary incontinence that provided at least 1 year
      of follow-up and that specified the suture material used. Outcomes of cases in
      which permanent suture was used were compared with cases in which absorbable
      suture was used. The groups were further stratified according to whether success
      of the procedure was determined objectively or subjectively. Chi-square analysis
      was performed. RESULTS: Fourteen case-series reports were examined, representing
      a total of 988 modified Pereyra operations. Overall, the relative risk (RR) of
      failure when absorbable suture was used was 1.8 times higher than with permanent
      suture (95% confidence interval [CI] 1.4-2.3; P < .0001) using objective or
      subjective outcome criteria. The RR of failure using absorbable suture when
      judged by objective criteria only was 1.6 (95% CI 1.1-2.3; P = .03) and when
      judged by subjective outcome only was 2.3 (95% CI 1.5-3.4; P < .0001).
      CONCLUSION: Until a randomized controlled trial is done, the available evidence
      supports the use of permanent suture material whenever the modified Pereyra
      procedure is performed.

PMID- 8272289
TI  - One hundred unstable bladders.
AB  - OBJECTIVE: To investigate the correlation between presenting symptoms and
      cystometric data in patients with urodynamically proven detrusor instability.
      METHODS: A retrospective review was conducted of standardized urodynamic data
      bases and cystometrograms from the gynecologic urodynamics laboratories at Duke
      University Medical Center, Durham, North Carolina, and Grady Memorial Hospital,
      Atlanta, Georgia. RESULTS: Of the 100 patients reviewed, 86% complained of urge
      incontinence and 78% complained of urinary urgency; however, 76% also complained
      of stress incontinence. Statistical evaluation of symptoms by analysis of
      variance showed no significant correlations between the symptoms of urinary
      frequency and urgency and any of the cystometric indices. Patients with motor
      urge incontinence had significantly smaller mean cystometric bladder capacities
      than patients without this complaint (299.9 +/- 132.5 versus 553.6 +/- 173.6 mL;
      P < .01). One-third (34) of the patients had mixed incontinence due to genuine
      stress incontinence as well as detrusor instability. Compared with patients
      suffering from detrusor instability alone, patients with mixed incontinence had
      significantly larger cystometric bladder capacities (396.0 +/- 172.9 versus 308.1
      +/- 154.8 mL; P < .02) and a lower amplitude of the maximum detrusor contraction
      (38.8 +/- 21.7 versus 49.9 +/- 25.1 cm H2O; P < .04). CONCLUSIONS: Women with
      detrusor instability represent a diverse population with a wide variety of
      symptoms and urodynamic findings. Patients with mixed incontinence may represent
      a subpopulation distinct from those with pure detrusor instability. Further
      research that attempts to describe other discrete subpopulations of patients with
      detrusor instability may improve our understanding of this troublesome clinical
      problem.

PMID- 8272290
TI  - Alternating weekly chemotherapy with etoposide-methotrexate
      dactinomycin/cyclophosphamide-vincristine for high-risk gestational trophoblastic
      disease.
AB  - OBJECTIVE: To evaluate the response rate and toxicity of alternating weekly
      therapy with etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine for
      women with high-risk gestational trophoblastic disease. METHODS: Twenty-two women
      with gestational trophoblastic disease received 126 cycles of the study regimen.
      Response was evaluated by serial hCG monitoring. Toxicity was assessed using
      standard criteria. RESULTS: Six women (27%) were treated for primary therapy and
      16 (73%) for secondary therapy. The median prognostic index score was 11 (range 7
      19). Only 23% of the patients and 11% of the 126 treatment cycles had grade 4
      neutropenia, despite the heavily pretreated patient population. Only 2% of the
      cycles were associated with neutropenic sepsis or required platelet transfusions.
      Nonhematologic toxicity was modest. Among 16 women who received chemotherapy
      alone, there were 11 (69%) complete and three (19%) partial responses. When
      adjuvant therapies are included, the overall complete and partial response rates
      were 77 and 14%, respectively. Six (35%) of 17 complete responders developed
      recurrences. Five patients with partial response or relapse were salvaged with
      additional therapy. Fifteen of the 22 patients (68%) have sustained remissions.
      CONCLUSION: The regimen of alternating weekly etoposide-methotrexate
      dactinomycin/cyclophosphamide-vincristine is effective and well-tolerated
      chemotherapy for patients with high-risk gestational trophoblastic disease.

PMID- 8272291
TI  - Mutation and overexpression of the p53 tumor suppressor gene frequently occurs in
      uterine and ovarian sarcomas.
AB  - OBJECTIVE: To determine the frequency of mutation and overexpression of the p53
      tumor suppressor gene in female genital tract sarcomas. METHODS: Immunostaining
      for p53 was performed in frozen sections of 46 ovarian and uterine sarcomas.
      Single-stranded conformation polymorphism analysis of exons 4-9 of the p53 gene
      was performed in 33 sarcomas. We performed DNA sequencing of the p53 gene in 22
      cases in which we found p53 protein overexpression and/or shifted bands on single
      stranded conformation polymorphism analysis. RESULTS: Overexpression of p53 was
      seen in 27 of 46 sarcomas (59%), including 26 of 41 (63%) mixed mesodermal
      tumors, one of four (25%) leiomyosarcomas, and zero of one endometrial stromal
      sarcoma. Among the 33 sarcomas subjected to molecular analysis, 21 demonstrated
      mutations in the p53 gene (64%). Eighteen cancers had a single mutation, whereas
      three cases showed two mutations in the p53 gene. There was one mutation in exon
      4, seven mutations in exon 5, three mutations in exon 6, six mutations in exon 7,
      six mutations in exon 8, and one mutation in exon 9. With the exception of one
      microdeletion, which predicted a truncated protein product, all of the mutations
      were missense point mutations. All but one of the point mutations resulted in
      changes in the predicted amino acid sequence. There were 18 transition mutations
      (75%), five transversions (21%), and one deletion (4%). CONCLUSIONS: Mutation of
      the p53 tumor suppressor gene, with resultant overexpression of p53 protein,
      frequently occurs in ovarian and uterine sarcomas. Because most of the mutations
      are transitions, p53 mutations in these cancers likely arise from spontaneous
      errors in DNA synthesis and repair rather than from exposure to carcinogens.

PMID- 8272292
TI  - Estrogen therapy in the management of urinary incontinence in postmenopausal
      women: a meta-analysis. First report of the Hormones and Urogenital Therapy
      Committee.
AB  - OBJECTIVE: To apply a meta-analysis to available data to evaluate the efficacy of
      estrogen therapy in the management of postmenopausal women with urinary
      incontinence. METHODS: The literature review incorporated English language
      articles based on a search of EXCERPTA MEDICA, BIOSIS, and MEDLINE from January
      1969 to June 1992. Criteria included: peer-reviewed original article, confirmed
      diagnosis of urinary incontinence, an estrogen-treated group, and outcome data on
      subjective improvement, quantitation of fluid loss, or maximum urethral closure
      pressure. In addition, the data had to allow comparison between treated and
      control groups in controlled trials or an estimated change in uncontrolled
      series. meta-analytic methods were applied only to studies considered to be
      controlled clinical trials. RESULTS: Of 166 articles reviewed, 143 did not meet
      the entry criteria; six were considered controlled clinical trials and 17 were
      uncontrolled series. Meta-analysis found an overall significant effect of
      estrogen therapy on subjective improvement for all subjects (P < .01) and for
      subjects with genuine stress incontinence alone (P < .05). The results showed no
      significant effect on quantity of fluid loss but a significant effect (P < .05)
      on maximum urethral closure pressure. However, the latter result was influenced
      by only one study showing a large effect. CONCLUSION: It appears from this
      analysis that estrogen subjectively improves urinary incontinence in
      postmenopausal women. However, the studies included nonhomogeneous groups, and
      the diagnostic criteria, therapeutic interventions, and outcome assessments
      varied considerably.

PMID- 8272293
TI  - Flow characteristics in benign and malignant gynecologic tumors using
      transvaginal color flow Doppler.
AB  - OBJECTIVE: To assess flow characteristics of benign and malignant gynecologic
      tumors by transvaginal color flow Doppler. METHODS: Records of the Ultrasound
      Laboratory, Women's Cancer Center, University of Minnesota were analyzed
      retrospectively. Gray scale findings were recorded as either "diagnostic" or
      "nondiagnostic." Color flow assessment was performed on intratumor vessels or
      ovarian and/or uterine arteries. Flow was recorded as either "absent" or
      "present." Spectral analysis allowed determination of the systolic, diastolic,
      and mean velocities and calculation of the pulsatility and resistance indices.
      Malignancy was then predicted based upon color flow findings alone, with
      malignant tumors demonstrating increased color flow and a pulsatility index of at
      most 1.0 or a resistance index of at most 0.4. Color flow Doppler findings were
      then recorded as "giving additional useful information" that either confirmed
      questionable gray scale findings or changed the gray scale sonographic diagnosis,
      or as "not giving additional information" over the gray scale diagnosis. RESULTS:
      Two hundred thirty-one patients had gray scale sonography, and 167 also had color
      flow Doppler performed. Gray scale sonographic findings were sufficient to make a
      diagnosis in 156 (93%) of the scans. Color flow Doppler findings added useful
      information in 49 scans (30%). Increased color flow was highly significant (P <
      .0001), as was the calculated pulsatility index (P < .02) and resistance index (P
      < .008), in distinguishing benign from malignant tumors. Ovarian and uterine
      artery and intratumor assessments of the systolic, diastolic, and mean velocities
      were not significantly different between the benign and malignant tumors.
      Regression analysis confirmed the presence or absence of color flow as an
      independent predictor of malignancy or benignity (P < .0001). CONCLUSIONS: Our
      large study confirms the overall accuracy of gray scale scanning. When used
      alone, color flow Doppler--although specific--lacks sensitivity and predictive
      value as an independent predictor of malignancy. When findings were combined with
      those obtained from gray scale scanning, sensitivity, specificity, and predictive
      value were improved to acceptable levels. Significant differences existed between
      benign and malignant tumors for calculated pulsatility index and resistance
      index, but neither was sufficiently sensitive, specific, or predictive to be used
      alone as sole criteria of malignancy prediction. Other flow indices studied
      (systolic, diastolic, and mean velocities) in general did not differ
      significantly between groups. Physicians should be cautioned against using color
      flow findings alone for clinical decision making. We recommend a multi
      institutional study to investigate the multiple vascular assessments to determine
      the role of color flow Doppler in the preoperative prediction of pelvic tumors
      and in screening for gynecologic abnormality.

PMID- 8272294
TI  - Quality assurance: measuring its effect on a busy obstetric service.
AB  - OBJECTIVE: To evaluate the effect of establishing a new quality assurance program
      in obstetrics at a large teaching hospital. METHODS: Seven obstetric clinical
      indicators were selected. After the computerized data base identified the
      patients as outliers from these indicators, the medical record of each patient
      was reviewed. Each case was presented to the nine-member committee, which made
      recommendations or actions for changes or improvement in patient care. The number
      of patients coming to review and the number of clinical indicators from the year
      before the program were compared to the results of the second year of the
      program. RESULTS: The new program significantly reduced the number of patient
      records reviewed and the clinical indicators. Of the clinical indicators,
      prolonged hospitalization after both vaginal and cesarean births was decreased.
      Recommendations to the department included the need for better chart
      documentation, specific educational presentations as grand rounds, and a protocol
      for antibiotic use for postpartum endomyometritis. CONCLUSION: A quality
      assurance program in obstetrics may decrease the number of clinical indicators
      after only 1 year. This decreasing trend and better documentation may be
      considered as measures of improvement in obstetric care.

PMID- 8272295
TI  - Maternal neurosurgical shunts and pregnancy outcome.
AB  - OBJECTIVE: To assess pregnancy outcome in women with ventriculoperitoneal or
      lumboperitoneal shunts. METHODS: Charts were reviewed retrospectively for mothers
      with ventriculoperitoneal or lumboperitoneal shunts delivered at Hutzel Hospital
      from 1976-1992. Patients were identified by cross-referencing medical records
      from Children's Hospital Neurosurgical Division and medical records at Hutzel
      Hospital during this period. RESULTS: Eight patients with 25 pregnancies were
      identified from 1976-1992. Indications for shunt placement were pseudotumor
      cerebri (four with lumboperitoneal shunts) and congenital hydrocephalus (four
      with ventriculoperitoneal shunts). Pregnancy outcomes were two elective
      abortions, five spontaneous abortions, two preterm vaginal deliveries, one mid
      forceps rotation, two primary low transverse cesareans, two repeat low transverse
      cesareans, and 11 spontaneous vaginal deliveries. No patient received
      prophylactic antibiotics during labor and vaginal delivery because of the shunt.
      There were no shunt-related complications. CONCLUSIONS: This series doubles the
      number of previously reported pregnancy outcomes in women with neurosurgical
      shunts. Contrary to the literature suggesting cesarean delivery and prophylactic
      antibiotics for all patients, our experience suggests that vaginal delivery can
      be considered and that prophylactic antibiotics are not an absolute necessity in
      uncomplicated vaginal deliveries.

PMID- 8272296
TI  - Extrafascial wound dehiscence: deep en bloc closure versus superficial skin
      closure.
AB  - OBJECTIVE: To determine closure time, pain experienced during closure, and
      healing time in patients undergoing deep en bloc closure or superficial skin
      closure of extrafascial would dehiscence. METHODS: Patients with extrafascial
      wound dehiscence on the obstetrics and gynecology service of the University of
      Mississippi Medical Center were randomized to deep en bloc closure or superficial
      skin closure. A 1:2 ratio was used to evaluate superficial skin closure, as deep
      en bloc closure is known to be effective. The wounds of patients in the deep en
      block group were closed with no. 1 polypropylene placed through the entire wound
      thickness as simple interrupted sutures. The wounds of patients in the
      superficial closure group were closed with 2-0 polypropylene placed through the
      skin as vertical mattress sutures. The wounds were closed on the patient care
      unit under local anesthesia. Closure was timed in minutes from initiation of
      local anesthesia to cutting of the last suture. Patients assessed pain by placing
      a mark on a 100-mm line (0 = none; 100 = maximum). Time for complete healing was
      measured from wound disruption to skin reepithelialization. RESULTS: During an 8
      month period, seven patients were randomized to deep en bloc closure and 16 to
      superficial skin closure. The en bloc group required 27.1 +/- 5.5 minutes (mean
      +/- standard deviation) for closure, compared with 18.9 +/- 3.4 minutes in the
      superficial group (P < .001). The mean pain score in the en bloc group was 43.4
      +/- 23.2 mm, compared with 16.6 +/- 11.4 mm in the superficial group (P < .001).
      The en bloc group required 22.7 +/- 7.7 days for complete healing, compared with
      19.8 +/- 5.3 days in the superficial group, a nonsignificant difference.
      CONCLUSIONS: Superficial skin closure of extrafascial wound dehiscence appears to
      be superior to deep en bloc closure in terms of closure time and pain experienced
      during the procedure. These benefits are achieved with minimal risk while
      allowing timely wound healing.

PMID- 8272297
TI  - Increased platelet volume and aggregation precede the onset of preeclampsia.
AB  - OBJECTIVE: To determine whether changes in platelet aggregation, numbers, or mean
      volume precede the onset of preeclampsia in patients given anti-platelet therapy.
      METHODS: Changes in platelet aggregation, numbers, and volumes were followed
      longitudinally in 17 women who had previously lost 44 of 56 pregnancies and were
      thus considered to be at risk of preeclampsia. The subjects were treated with low
      dose aspirin. Mean platelet volume, platelet numbers, and platelet aggregation
      were monitored every 2-4 weeks during pregnancy. RESULTS: All eight subjects who
      developed preeclampsia delivered growth-retarded infants before term. All showed
      increased platelet aggregation in vitro, accompanied by increased platelet
      volumes (by at least 0.8 fL) and decreased platelet numbers (by at least 60 x
      10(9)/L) in five subjects, increased volumes alone in one, and decreased numbers
      alone in one. The increases in platelet aggregation and volumes predated the
      development of preeclampsia by 2-5 weeks. Nine subjects had pregnancies that
      progressed normally to term (beyond 37 weeks), with the delivery of eight normal
      and one growth-retarded infant; platelet aggregation, numbers, and volumes did
      not change to the same extent as in the subjects who developed preeclampsia.
      CONCLUSION: Increased mean platelet volume and increased platelet aggregation
      compared to the individual patient's first-trimester data were detected 2-5 weeks
      before the development of all cases of preeclampsia. In contrast, normal
      pregnancies did not show significant changes in mean platelet volume or platelet
      aggregation.

PMID- 8272298
TI  - Modified median episiotomy minimizes the risk of third-degree tears.
AB  - The standard median episiotomy can be easily modified by adding two half-inch
      transverse cuts in opposite directions in the perineal fascia just above the anal
      sphincter. The use of this new technique, which is referred to as a modified
      median episiotomy, increases the diameter at the vaginal outlet 83% more than
      that provided by a median episiotomy alone. The increased diameter is also 10%
      greater than a mediolateral episiotomy alone. When an episiotomy is indicated,
      the exclusive use of this procedure makes the occurrence of third-degree tears
      extremely rare. The episiotomy is easy to repair.

PMID- 8272299
TI  - Gynecologic tumors in tamoxifen-treated women with breast cancer.

PMID- 8272300
TI  - Randomized comparison of home uterine activity monitoring and routine care in
      patients discharged after treatment for preterm labor.

PMID- 8272301
TI  - Effect of continuous combined estrogen and desogestrel hormone replacement
      therapy on serum lipids and lipoproteins.
AB  - OBJECTIVE: To determine the effects of continuous combined hormone replacement
      therapy with desogestrel and 17 beta-estradiol (E2) on serum lipids and
      lipoproteins. METHODS: Fifty-seven healthy postmenopausal women of less than 60
      years of age were studied prospectively and treated with oral desogestrel 0.15
      mg/day and micronized 17 beta-E2 1 mg/day, both taken continuously. Fasting
      venous blood samples for serum lipids and lipoproteins were taken before and
      after 6 and 12 months of treatment. RESULTS: Thirty-two women completed the
      study. Levels of all serum lipids and lipoproteins fell significantly by 6 months
      and remained low at 12 months. The mean percentage reduction after 12 months of
      treatment was 12.8% for high-density lipoprotein (HDL) cholesterol, which largely
      resulted from a reduction in the HDL2 subfraction, which fell by 25.7%. The mean
      percentage reduction for both low-density lipoprotein (LDL) cholesterol and
      triglycerides was 7.7%. The median percentage reduction for lipoprotein (a) was
      17.6%. CONCLUSIONS: This combination of hormone replacement therapy had profound
      effects on serum lipids and lipoproteins. According to current concepts,
      reductions in total and LDL cholesterol, triglycerides, and lipoprotein (a) may
      reduce cardiovascular disease risk. The reduction in HDL was unexpected, given
      the rise in HDL that has been demonstrated when desogestrel is combined with
      ethinyl estradiol in the contraceptive pill. The lowering of HDL observed in this
      study is undesirable and may be potentially harmful. Our results indicate that
      when desogestrel 0.15 mg/day is combined with micronized 17 beta-E2 1 mg/day in a
      continuous manner, the effects of the progestogen on HDL predominate and cause a
      reduction in HDL and the HDL2 subfraction.

PMID- 8272302
TI  - No adverse effects of medroxyprogesterone treatment without estrogen in
      postmenopausal women: double-blind, placebo-controlled, crossover trial.
AB  - OBJECTIVE: To determine whether cyclic medroxyprogesterone treatment given
      without estrogen causes adverse symptoms in postmenopausal women. METHODS: This
      was a placebo-controlled, double-blind, crossover trial of 10 days/month of
      medroxyprogesterone and placebo treatments given during 2 consecutive months in
      random order. Participants recorded their physiologic and emotional experiences
      on a 0-4 scale using a daily diary form. Eleven postmenopausal women aged 43-63
      completed the study. The subjects were not taking hormones. Height, weight, and
      serum estradiol concentration were measured once. In each woman, the sum of
      scores for the 10 days of medroxyprogesterone was compared to the sum of scores
      for the 10 days of placebo using nonparametric tests. RESULTS: No significant
      differences in scores were found between the 10 days on medroxyprogesterone and
      the 10 days on placebo. The median and range for the composite scores for
      premenstrual-like symptoms were 26 (20-67) during medroxyprogesterone and 25 (19
      40) during placebo (P = .39). CONCLUSIONS: Medroxyprogesterone given alone does
      not cause adverse symptoms in postmenopausal women. Therefore,
      medroxyprogesterone therapy, by itself, cannot explain the side effects reported
      by postmenopausal women taking combined hormones.

PMID- 8272303
TI  - Ovulation and follicular development associated with three low-dose oral
      contraceptives: a randomized controlled trial.
AB  - OBJECTIVE: To address the hypothesis that multiphasic oral contraceptives (OCs)
      increase rather than decrease the risk of functional ovarian cysts. METHODS: In
      this single-center, randomized controlled study, women were assigned to a
      multiphasic pill, a lower-dose monophasic pill, a higher-dose monophasic pill, or
      nonsteroidal contraception. Forty volunteers were randomized (ten each) to three
      different pill regimens or to nonsteroidal contraception. During 6 months of
      treatment, follicular development was measured by vaginal ultrasonography and
      ovulation was indicated by serum progesterone levels. RESULTS: The relative risk
      (RR) of developing a follicular structure greater than 30 mm in diameter during a
      cycle with the higher-dose monophasic pill was 0.5 (95% confidence interval [CI]
      0.1-1.9; P = .49) compared with the multiphasic pill. The risk with the lower
      dose monophasic pill was comparable to that with the multiphasic pill (RR 1.3,
      95% CI 0.5-3.6; P = .56). With the multiphasic pill, the maximum ovulation rate
      over 60 cycles was 1.7 per 100 cycles (95% CI 0.0-8.9). CONCLUSION: This
      multiphasic pill more closely resembled the lower-dose monophasic pill than the
      higher-dose monophasic pill in its suppression of follicular development.

PMID- 8272304
TI  - Natural history of twin pregnancy with complete hydatidiform mole and coexisting
      fetus.
AB  - OBJECTIVE: To investigate the clinical features and natural history of twin
      conceptions consisting of complete hydatidiform mole and a coexisting fetus.
      METHODS: Since 1973, eight well-documented cases of twin pregnancy with complete
      hydatidiform mole and coexisting fetus have been treated at the New England
      Trophoblastic Disease Center (NETDC). The clinical features of these eight
      patients were compared to 71 patients with singleton complete hydatidiform mole
      treated at the NETDC and with the published experience of other investigators.
      Flow cytometric analysis of DNA content was performed in addition to histologic
      inspection to assist in confirming the diagnosis of twin pregnancy with complete
      hydatidiform mole and coexisting fetus. RESULTS: Five of the eight patients in
      this series developed persistent gestational trophoblastic tumor requiring
      chemotherapy. Three of these five patients developed metastases requiring multi
      agent chemotherapy to achieve remission. The presenting symptoms of twin
      pregnancy with complete hydatidiform mole and coexisting fetus were similar to
      those in patients with a singleton complete mole. However, compared to singleton
      complete molar gestation, a twin pregnancy with complete mole and coexisting
      fetus was diagnosed at a later gestational age, had higher preevacuation beta-hCG
      levels, and had a greater propensity to develop persistent gestational
      trophoblastic tumor. CONCLUSION: Our findings indicate that patients with
      complete hydatidiform mole and coexisting fetus are at high risk for developing
      persistent gestational trophoblastic tumor.

PMID- 8272305
TI  - The effect of 25-mg percutaneous estradiol implants on the bone mass of
      postmenopausal women.
AB  - OBJECTIVE: To determine whether the lowest available dose of percutaneous
      implant, 25 mg estradiol (E2), is effective for the prevention of postmenopausal
      bone loss. METHODS: Eighteen healthy postmenopausal women were treated with 25-mg
      percutaneous E2 implants for 1 year. Dual energy x-ray absorptiometry was
      performed at the lumbar spine and proximal hip using a quantitative digital
      radiography densitometer before treatment and after 1 year. Estradiol and FSH
      were also measured before and after 1 year of treatment. The changes in bone
      mineral density were compared with a matched reference group of 18 women who did
      not wish treatment. RESULTS: The median percentage changes in the treated group
      after 1 year were 5.65% at the lumbar spine, 3.38% at the femoral neck, and 3.36%
      total hip. At 1 year, there was a significant increase in bone mineral density
      from baseline at all sites measured except Ward triangle. The median post
      treatment E2 level was 320 pmol/L (range 114-813), and FSH was 28 IU/L (range 2
      66). CONCLUSION: This study demonstrates that 25-mg percutaneous E2 implants
      significantly increase bone mineral density at the spine and hip in
      postmenopausal women. This dose is effective to prevent postmenopausal bone loss.

PMID- 8272306
TI  - Vulvar vestibulitis syndrome: an exploratory case-control study.
AB  - OBJECTIVE: To assess the prevalence of genital bacterial infection among women
      with vulvar vestibulitis syndrome and to evaluate the association of several
      potential risk factors with the occurrence of the syndrome. METHODS: Fifty-seven
      women referred for dyspareunia who satisfied Friedrich's criteria and had
      symptoms for at least 6 months were recruited as cases. Controls included 173
      patients without dyspareunia seen at a private clinic. Cases and controls were
      aged 18-35 years and were not pregnant. RESULTS: Among cases, the prevalences
      were low for genital infection with gonorrhea (0%), Chlamydia (0%), Trichomonas
      (0%), Mycoplasma (0%), Gardnerella (14%), and Candida (8.8%). Ureaplasma was
      detected in the Bartholin glands of ten affected women (17.5%). Human
      papillomavirus DNA was detected in only three cases (5.3%) based on polymerase
      chain reaction assays on vestibular biopsies. The relative risk (RR) of the
      syndrome was related to some aspects of sexual and reproductive history. In
      particular, the RR in women who had used oral contraceptives (OCs) early (before
      age 17) reached 11.0 (95% confidence interval [CI] 1.3-97.1) relative to those
      who had never used OCs. Women who had first intercourse at age 15 or earlier had
      a 3.3-fold increase in RR (95% CI 1.4-8.0) compared to those who had first
      intercourse at age 16 or later. CONCLUSION: Our data provide little support for
      the idea that infection causes the vulvar vestibulitis syndrome. Hormonal factors
      such as early OC use may be involved in the etiology of this condition.

PMID- 8272307
TI  - Postmenopausal hormone use and cholecystectomy in a large prospective study.
AB  - OBJECTIVE: To examine the association between postmenopausal hormone use and
      cholecystectomy. METHODS: A prospective cohort study was performed, with follow
      up every 2 years. Participants were 54,845 postmenopausal United States nurses,
      who reported both hormone use and cholecystectomy on mailed questionnaires.
      RESULTS: Cholecystectomy was reported by 1750 women during 8 years of follow-up.
      After adjusting for confounding factors, women currently using postmenopausal
      hormones were at an increased risk of cholecystectomy (relative risk [RR] 2.1,
      95% confidence interval [CI] 1.9-2.4) compared to never-users. For current users,
      the risk of cholecystectomy increased with increasing duration of hormone use (RR
      2.6, 95% CI 2.2-3.1 for 10 years or more) and higher doses of estrogen (RR 2.4,
      95% CI 2.0-2.9 for users of 1.25 mg or more). Although the risk for past hormone
      users decreased substantially in women who had discontinued use 1-2.9 years ago
      (RR 1.6, 95% CI 1.2-2.0), a small risk persisted for women who had stopped taking
      hormones 5 or more years previously (RR 1.3, 95% CI 1.1-1.6). However, after
      controlling for time since last use, duration of past use had little or no effect
      on the risk of cholecystectomy (RR 1.4 and RR 1.7 for past users of less than 2
      years and 10 or more years' duration, respectively). CONCLUSION: Women using
      postmenopausal hormones are at an increased risk of cholecystectomy. Women and
      their physicians should consider the spectrum of risks and benefits when deciding
      whether to take hormones.

PMID- 8272308
TI  - Single-dose systemic methotrexate for the treatment of persistent ectopic
      pregnancy after conservative surgery.
AB  - OBJECTIVE: To determine whether a single outpatient methotrexate injection
      successfully treats persistent ectopic pregnancy. METHODS: Nineteen consecutive
      patients with increasing beta-hCG titers after conservative surgery for ectopic
      pregnancy were treated with a single intramuscular methotrexate (50 mg/m2)
      injection. RESULTS: All 19 patients had resolution of their beta-hCG titers
      without subsequent surgery. Beta-hCG levels commonly increased during the first 3
      days after treatment, but subsequently declined. Two patients required hospital
      admission for observation and analgesia. One of these two patients had probable
      self-limited intra-abdominal bleeding and required a blood transfusion.
      CONCLUSION: A single methotrexate injection is a safe and successful treatment
      for persistent ectopic pregnancy. Delayed hemorrhage may be a rare complication,
      and close surveillance is necessary.

PMID- 8272309
TI  - An updated protocol for abortion surveillance with ultrasound and immediate
      pathology.
AB  - OBJECTIVE: To modify and improve a protocol for surveillance of patients
      presenting for routine elective abortion services. METHODS: Six hundred seventy
      four women presenting for routine elective first-trimester abortions were
      studied. All were 84 or fewer days after the last menstrual period, had no
      history of bleeding, and had positive urine pregnancy tests. Each woman was
      scanned initially with an empty-bladder transabdominal technique. If no sac was
      seen, endovaginal ultrasonography was performed. All terminations had modified
      gross examination of tissue (3x magnification) as well as staining for
      microscopic analysis. RESULTS: Six hundred twelve patients (90.8%) demonstrated
      intrauterine gestations on transabdominal ultrasound, 595 of which were 12 or
      fewer weeks. Suction and sharp curettage and examination of tissue revealed
      products of conception in all. Seventeen subjects (2.5%) were found to be 13 or
      more weeks despite bimanual examinations and last menstrual period suggesting 12
      or fewer weeks. Sixty-two patients had no sac seen on transabdominal ultrasound,
      34 of whom had definitive intrauterine gestations on endovaginal ultrasound.
      Curettage revealed chorionic villi in all. Two had unruptured definitive ectopic
      pregnancies seen on endovaginal ultrasound. Twenty-one women with no sac seen on
      endovaginal ultrasound underwent curettage as the next step in triage; chorionic
      villi proved an intrauterine gestation in 17. The additional four had decidua
      only on pathology. Rising hCG levels in two of these four led to a diagnosis of
      ectopic pregnancy, whereas falling hCG levels in the other two led to a
      presumptive diagnosis of complete abortion, possibly tubal pregnancy in light of
      the lack of vaginal bleeding. CONCLUSION: Pre-abortion sonography eliminates
      inadvertent second-trimester cases, and immediate postoperative examination of
      curettage material expedites the diagnosis of ectopic pregnancy when present.

PMID- 8272310
TI  - Prevention of postoperative adhesions in the rat by in situ photopolymerization
      of bioresorbable hydrogel barriers.
AB  - OBJECTIVE: To assess the efficacy of a novel resorbable hydrogel barrier for
      preventing postoperative adhesions in animals. METHODS: A hydrogel barrier was
      formed in situ by photopolymerizing a solution of a macromolecular prepolymer in
      buffered saline using long-wavelength ultraviolet light. Two models in the rat
      were evaluated. In a primary adhesion model, devascularization and serosal injury
      were performed on the uterine horns using bipolar electrocautery. The prepolymer
      solution was applied to the horns and illuminated to form the barrier. On the
      seventh postoperative day, the fraction of the length of the horns involved in
      adhesions was scored, as was the quality of the adhesions. In a readhesion model,
      adhesions were formed as described and were surgically lysed on the seventh day,
      then were treated subsequently with the barrier and scored after 7 additional
      days. Each group in both models consisted of seven animals per treatment
      condition. Four prepolymer concentrations were examined in the primary adhesion
      model, and the optimal one was examined in the readhesion model. RESULTS: A
      conformal hydrogel barrier coating was formed upon in situ photopolymerization
      and adhered to the treated tissues. No residual hydrogel barrier was observed 7
      days after application of the optimal gel concentrations. In the primary adhesion
      model, the mean fraction of the horns involved in adhesions was reduced
      significantly, from 76% in controls to 10% (P < .0001), and treatment with a 10%
      solution of prepolymer was determined to be optimal (P = .025). In the readhesion
      model, surgical lysis of adhesions alone did not reduce adhesions significantly
      (from 86% to 79%; P = .3), whereas lysis with barrier treatment did (79% to 28%;
      P = .002). CONCLUSIONS: In situ photopolymerization allowed the formation of
      adherent, conformal barriers, which demonstrated high efficacy in the prevention
      of adhesion formation and reformation in animals. This efficacy and ease of use
      warrant clinical evaluation.

PMID- 8272311
TI  - Maternal and fetal platelet activation in normal pregnancy.
AB  - OBJECTIVE: To study the platelet activation phase in normal pregnant women and
      their fetuses, both in vivo under basal conditions and in vitro after stimulation
      by adenosine diphosphate (ADP), a weak agonist, and U46619, a strong one.
      METHODS: Platelet function was investigated in 39 normal pregnant women and their
      fetuses undergoing fetal blood sampling at 18-37 weeks' gestation, using flow
      cytometry and the anti-GMP140 monoclonal antibody. This combined technique allows
      platelets to be investigated in small aliquots of whole blood, and it detects
      platelet secretion regardless of aggregation. In all cases, the percentage of
      activated platelets was determined under basal conditions and after addition of
      platelet agonists: ADP at concentrations of 10 and 50 mumol/L, and U46619, a
      stable analogue of thromboxane A2, at 1 mumol/L. RESULTS: Compared to nonpregnant
      controls, pregnant women had a significantly lower percentage of activated
      platelets after addition of U46619 (P = .02). Compared to their mothers, fetuses
      had significantly inferior platelet activation after addition of both platelet
      activating factors at all concentrations used (ADP 10 mumol/L, P < .0001 and ADP
      50 mumol/L, P < .0001; U46619, P < .0001). Maternal and fetal platelet activation
      did not change with duration of gestation. In the fetus, the percentage of
      activated platelets did not correlate with hematocrit, pH, or oxygen pressure,
      but it correlated significantly with platelet count after addition of U46619 (r =
      0.45, P = .006). CONCLUSIONS: Decreased platelet activation in both pregnant
      women and fetuses suggests the action of a plasma factor that selectively
      inhibits prostaglandin-dependent activation. Prostacyclin, which is known to
      decrease platelet aggregation and release reactions caused by agonists, might
      have a greater inhibitory effect in the fetus than in the mother, or be present
      in larger amounts in the fetus.

PMID- 8272312
TI  - Antepartum vitamin K and phenobarbital for preventing intraventricular hemorrhage
      in the premature newborn: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVE: To determine whether antepartum phenobarbital and vitamin K reduce the
      risk of intraventricular hemorrhage in premature newborns. METHODS: Patients at
      imminent risk for spontaneous or indicated premature delivery between 24-34
      weeks' gestation were randomized to receive either placebo or vitamin K and
      phenobarbital. All patients received betamethasone and antibiotics and were
      managed uniformly by a single perinatal group in one hospital. All newborns were
      managed uniformly in the same facility by a single neonatal group. RESULTS: There
      was a nonsignificant reduction in all grades of intraventricular hemorrhage in
      the treatment group when compared to the placebo group (48.2 versus 38.3%; P >
      .05). Frequencies were reduced for severe intraventricular hemorrhage (grades 3
      and 4) (6.0 versus 2.5%; P > .05) and mild intraventricular hemorrhage (grades 1
      and 2) (42.2 versus 35.8%; P > .05). CONCLUSIONS: Antepartum phenobarbital and
      vitamin K effected a nonsignificant reduction in both mild and severe
      intraventricular hemorrhage. The incidence of severe intraventricular hemorrhage
      in our control group was significantly less than that observed in previous
      studies.

PMID- 8272313
TI  - Meconium-stained amniotic fluid and respiratory complications: impact of
      selective tracheal suction.
AB  - OBJECTIVE: To determine prospectively the incidence of several pulmonary
      diagnoses among infants born through clear or meconium-stained amniotic fluid
      (AF) managed by a selective approach to tracheal intubation. METHODS: All live
      births greater than 36 weeks' gestation occurring between January 1990 and
      December 1992 were included. Diagnostic criteria for several respiratory
      disorders were determined prospectively and monitored. Infants with light
      meconium and vigorous infants with moderate to thick meconium were selectively
      not suctioned. A control group of infants with clear AF matched for gestational
      age and year of birth was randomly selected for comparison. The incidence and
      severity of respiratory disease were compared between the groups. RESULTS: Of
      4938 live births, 799 (16%) had meconium-stained AF (light, 334; moderate to
      thick, 465). Compared to 211 infants with moderate to thick meconium selectively
      not suctioned, 196 suctioned infants had significantly greater rates of abnormal
      fetal heart rate (FHR) patterns, fetal acidosis, low Apgar scores at 5 minutes,
      need for resuscitation, and neonatal intensive care unit admission. Meconium
      aspiration syndrome was significantly more common in suctioned infants as
      compared to those selectively not suctioned, those with light meconium, and those
      with clear fluid (11 versus 3 versus 0 versus 0%; P < .01). The need for
      ventilator or oxygen support was similar between infants with clear fluid,
      lightly stained fluid, and moderate to thick fluid who were selectively not
      suctioned, but was significantly greater among suctioned infants (P < .01).
      CONCLUSIONS: We conclude that a selective approach to tracheal intubation and
      suction of infants with meconium-stained AF was not associated with increased
      pulmonary morbidity or mortality. Postnatal management of neonates at greatest
      risk of meconium aspiration syndrome does not necessarily prevent adverse
      pulmonary outcome.

PMID- 8272314
TI  - Effect of short-term infusion of recombinant human relaxin on blood pressure in
      the late-pregnant rhesus macaque (Macaca mulatta).
AB  - OBJECTIVE: To test a recombinant human relaxin preparation, developed for
      potential therapeutic application, for possible hypotensive actions in near-term
      pregnant rhesus monkeys. METHODS: Groups of four females received 1-hour
      intravenous infusions of 0, 0.1, or 2.0 mg recombinant human relaxin/kg on
      gestation day 147 (term = 165 days). Maternal heart rate, electrocardiogram, and
      diastolic, systolic, and mean arterial pressure; and fetal heart rate were
      monitored before, during, and after the infusion. After spontaneous delivery,
      physical, neurobehavioral, and physiologic examinations were conducted on the
      newborn. RESULTS: No effects of recombinant human relaxin were detected by
      statistical analysis or examination of data records. CONCLUSION: Intravenous
      infusion of up to 2.0 mg recombinant human relaxin/kg in conscious pregnant
      rhesus monkeys had no effect on maternal cardiovascular indices or fetal heart
      rate.

PMID- 8272315
TI  - Central hemodynamic effects of cocaine and ritodrine in the isolated, perfused
      rat heart.
AB  - OBJECTIVE: To explore the cardiac interactions of cocaine and ritodrine in
      pregnancy. METHODS: Using the isolated, perfused rat-heart model, hearts from
      pregnant Sprague-Dawley rats were exposed to increasing concentrations of
      ritodrine: 25, 50, 100, and 250 ng/mL. Hearts of half of the animals, the
      experimental group, were exposed to cocaine (5 x 10(-6) mol/L). Left ventricular
      systolic pressure, heart rate, and contractility were measured. RESULTS:
      Ritodrine had marked positive inotropic and chronotropic effects. Cocaine
      exposure resulted in smaller increases in all indices. CONCLUSION: Cocaine
      blunted but did not obliterate the cardiac stimulatory effects of ritodrine in
      this model.

PMID- 8272316
TI  - Endothelium-derived relaxing factor inhibition and the pressor response to
      norepinephrine in the pregnant rat.
AB  - OBJECTIVE: To determine whether endothelium-derived relaxing factor (EDRF) plays
      a role in the blunted pressor response to norepinephrine that is characteristic
      of normal pregnancy. METHODS: Eleven pregnant (mean +/- standard error of the
      mean 18 +/- 1 days of gestation) and 11 virgin conscious, unrestrained Sprague
      Dawley rats with long-term indwelling vascular catheters were studied. Mean
      arterial pressure (MAP) and heart rate were measured in response to continuous
      infusions of either vehicle (5% dextrose) or increasing concentrations of
      norepinephrine (25, 100, and 200 ng/kg/minute) before and after administration of
      NG-monomethyl-L-arginine (LNMMA), a specific inhibitor of EDRF synthesis.
      RESULTS: Baseline MAP was lower in pregnant than in virgin rats (96 +/- 3 versus
      105 +/- 3 mmHg; P < .05). Before LNMMA administration, the pregnant rats
      exhibited a significantly blunted pressor response to increasing concentrations
      of norepinephrine compared to that of virgin rats (P < .005). Given alone, LNMMA
      produced a greater increase in baseline MAP in virgin rats than in pregnant rats
      (rise in MAP of 44 +/- 2 versus 31 +/- 2 mmHg; P < .001). However, LNMMA
      abolished the blunted pressor response to norepinephrine in the pregnant animals
      and did not significantly affect the pressor response to norepinephrine in virgin
      rats. Heart rate responses to increasing concentrations of norepinephrine in the
      presence and absence of LNMMA were not significantly different in the two groups
      of animals. CONCLUSION: Stimulated EDRF production may contribute to the blunted
      pressor response to norepinephrine characteristic of pregnancy in the rat.

PMID- 8272317
TI  - Hot-knife conization of the cervix: clinical and pathologic findings from a study
      introducing a new technique.
AB  - OBJECTIVE: To introduce an alternative method for conization of the cervix using
      a Teflon-coated hot knife and to evaluate thermal distortion, adequacy of
      excision, operating time, blood loss, and short- and long-term effects of this
      method. METHODS: Between 1987-1993, 88 patients underwent cervical conization
      using a Teflon-coated hot knife at temperatures ranging from 110-130C.
      Histopathologic slides were reviewed simultaneously by two pathologists, who
      assessed thermal distortion, adequacy of excision, and interpretability of the
      surgical margins. Clinical information was obtained prospectively, including
      operating time, blood loss, and depth and volume of the excised cone. In
      addition, data were accumulated retrospectively from 40 randomly selected
      patients who underwent cold-knife conization between 1985-1990. Short- and long
      term data were assessed for healing and scarring and the adequacy of
      postoperative Papanicolaou smears in the hot-knife patients. RESULTS: Thermal
      injury was minimal, with 300 mu or less in 83 patients (92%) and 350-600 mu in
      four patients. One patient had thermal distortion of 1500 mu. All slides were
      interpreted adequately. Blood loss was mild to moderate in 84 of 88 patients
      (95%) in the hot-knife group and in 34 of 40 patients (85%) in the cold-knife
      group. No patient in the hot-knife group needed blood transfusion or
      hospitalization. Operating time was reduced by as much as 67% when the hot knife
      was used. Thirteen percent of the hot-knife patients developed stenosis of the
      external os. No patient in the hot-knife group developed recurrence within 2
      years of surgery. CONCLUSION: Using a Teflon-coated hot knife for conization of
      the cervix produces adequate surgical margins and reduces blood loss and
      operating time over that with cold-knife conization. Long-term follow-up reveals
      no increase in cervical stenosis and demonstrates adequate cytologic smears in
      the hot-knife patients.

PMID- 8272318
TI  - Distribution of protein kinase C in the villi of duodenum of developing chick
      embryos and chicks: immunohistochemical studies at the light and electron
      microscopic levels.
AB  - We examined the immunohistochemical localization of protein kinase C (PKC) in
      chick embryonic and chick duodenal villi contained in cultured duodena using
      monoclonal antibodies that recognize types 1, 2 and 3 at the light and electron
      microscopic levels. In the light microscopic studies, staining with the type 2
      and 3 PKC antibodies revealed immunoreactivities in the absorptive epithelial
      cells of the villi that approximated the time course after hatching, but was weak
      and partial just before the time of hatching. The epithelial cells of crypts
      seemed to lose their stain at all times. In the transmission electron microscopic
      studies, positive immunoreaction was found predominantly in the endoplasmic
      reticulum and nucleus, and also in the terminal web in the absorptive epithelial
      cells of villi. In the cultured duodenal fragments, a change in the distribution
      of PKC was observed on the sheet-like duodenal fragments and its immunoreaction
      was mainly seen on the basal side of absorptive cells. In contrast, no change in
      the staining of PKC was revealed on the ring-like duodenal fragments. These
      results suggested that PKC in the chick duodenal villi may be functionally
      related with the differentiation of absorptive epithelial cells and sensitive to
      changes in the cellular interactions of absorptive epithelial cells.

PMID- 8272319
TI  - Immunohistochemical detection of alkaline phosphatase in formalin-fixed and
      paraffin-embedded rat liver.
AB  - Alkaline phosphatase (ALP) in rat liver was detected by means of
      immunohistochemical techniques in ordinary histologic specimens which were fixed
      with formalin and embedded in paraffin. The specimens were incubated in anti-ALP
      antibody at room temperature for a longer time, 3hr, than ordinary incubation
      time. Antigen detection sensitivity and contrast of reaction product of the
      immunogold silver staining were superior to those of the peroxidase-labeled
      antibody method. In rat livers which were partially hepatectomized 24 hr before,
      the more abundant enzyme localized around enlarged bile canalicular spaces.

PMID- 8272320
TI  - Morphological study of the teeth of Ambystoma maculatum, Salamandra salamandra
      and Aneides lugubris: fine structure and chemistry of enamel.
AB  - The functional teeth of adult salamander (Caudata): Ambystoma maculatum,
      Salamandra salamandra and Aneides lugubris were prepared for transmission
      electron microscopy and electron microprobe analysis of the elements and trace
      elements of the enamel layer. The arrangement of enamel crystals in these species
      is variable. The outer part of the enamel layer in which hydroxyapatite elements
      (Ca, P) and trace elements (e.g., F, Fe, Mg) are concentrated, is most
      mineralized. The concentration of trace elements are arrangement of crystals in
      the enamel layer differed in these species, may be related to the pattern of
      mineralization of enamel.

PMID- 8272321
TI  - The sites and expansion of intra-embryonic blood islands in the early chick
      embryo.
AB  - The intraembryonic blood islands preceding the hepatic haemopoiesis, were
      examined in embryos from stage 17 to 19 by light microscopy, and their three
      dimentional expansion was demonstrated. These blood islands were located in the
      mesenchyme of the lateral fold, mesentery, allantois and ventral aorta, commonly
      showing large scale. Except the lateral fold, however, those were just temporary
      sites. Particularly large islands were necessarily found in the mesenchyme of the
      lateral fold at the stages examined. They were present bilaterally and exhibited
      cephalocaudally long, rod-like structures with variable sizes. The largest island
      measured over 2,600 microns in length.

PMID- 8272322
TI  - Electron microscopic nerve fiber caliber analysis in the nerve branches to the M.
      mylohyoideus in mouse.
AB  - Nerve fiber counts and caliber analysis of the nerve branches to m. mylohyoideus
      were performed with an electron microscope on 5 sides from 3 mice. The nerve
      branches contained an average of 93.6 (54.7%) myelinated fibers, 76.2 (44.6%)
      unmyelinated fibers and 1.7 (0.7%) undetermined fibers. 60.3% of the myelin
      sheaths of the myelinated fibers in the nerve branches were 3.5-6.0 microns in
      major diameter and 67.8% were 2.5-5.0 microns in minor diameter. 81.7% of the
      axons of the myelinated fibers were 1.5-4.5 microns in major diameter and 83.1%
      were 1.0-3.5 microns in minor diameter. The diameter frequency distributions of
      the myelin sheaths and axons of myelinated fibers in the nerve branches were
      similar in pattern to that of the facial trunk distal to the stylomastoid
      foramen. On the other hand, these frequency distributions of the nerve branches
      showed that the diameters of the myelinated fibers of the nerve branches were
      approximately 1-2 microns smaller than those of the r. digastricus, r.
      stylohyoideus and the nerve branch to venter rostralis of m. digastricus. Average
      ratios of the cross-sectional areas of myelin sheaths to those of axons of the
      myelinated fibers in the various axon area classes were 0.59-1.18, and those
      ratios tended to decrease in the larger axon classes.

PMID- 8272323
TI  - Anatomical observations on cleavage line patterns of the skin in adult pigs.
AB  - In six pigs from 7 months to 3 years of age the cleavage line pattern of the skin
      was examined in the whole body by a thick metal probe with a sharp conical point.
      Directionality of the cleavage lines was determined from the relationship of the
      line of the long axis of each physical structure. The cleavage lines of adult
      pigs were compared with those of young pigs (Wakuri, 1967). The cleavage lines of
      the ear, neck, trunk, and free extremities of appendage were quite similar in
      adult and young pigs. Those of the buccal, interscapular and sacral regions,
      umbilicus and scrotum showed slight differences. The most noticeable directional
      variability in cleavage lines appeared in the masticatory region, arms and legs
      of adult pigs. Cleavage lines were found to be transverse in arrangement in the
      masticatory region, auricular root, neck, trunk, tail and legs. They showed an
      annular pattern around the preputial orifice and in the arms and anogenital
      region.

PMID- 8272324
TI  - Experimental chlorphentermine lipidosis of the retina in albino rats.
AB  - Chronic administration of chlorphentermine leads to an accumulation of lysosomal
      inclusions in the retina of young rats. The cells of the pigment epithelium, the
      perikeratic part of the ganglial cells and their axones are filled with
      inclusions, whereas other parts of the retina remain free. As soon as the
      treatment is discontinued, the alterations recede completely. The experiment can
      be considered to be a model for the lysosomal capacity of those parts of the
      retina concerned; in addition, it supplies information on the metabolism of
      phospholipids in these structures.

PMID- 8272325
TI  - Breakdown of the blood-retinal barrier after radiofrequency-induced ocular
      hyperthermia.
AB  - To study the possible application of hyperthermia in the treatment of
      proliferative vitreoretinopathy (PVR), we induced hyperthermia in 15 normal
      rabbit eyes by a radiofrequency capacitive heating device. The retinal surface of
      each eye was warmed to a presumed temperature of 41 or 43 degrees C for 30 min.
      The thermal effect on the blood-retinal barrier (BRB) was evaluated before and 2
      h after the hyperthermic regimen by means of vitreous fluorophotometry. Heat
      treatment to 43 degrees C at the retinal surface for 30 min increased the
      fluorescein leakage compared with the 41 degrees C treatment. This finding
      suggests that retinal hyperthermia at 43 degrees C for 30 min may cause breakdown
      of the BRB.

PMID- 8272326
TI  - Bicanalicular silicone intubation using three-piece silicone tubing: direct
      silicone intubation.
AB  - The special silicone tube (50-120 mm in length) consists of three pieces. One
      piece is the thinner central segment [20-40 mm long, 0.64 mm outer diameter (OD),
      0.30 mm inner diameter (ID)], and the other two are thicker bilateral segments
      (10-50 mm long, 0.94 mm OD, 0.51 mm ID). Both ends of the three-piece silicone
      tubing (TPST) were sealed by the silastic medical adhesive with or without the
      silicone rod (2 mm long, 0.5 mm diameter) and diagonally cut to taper the end. To
      push the TPST from the upper and lower puncta into the lacrimal passage, a thin
      metal probe (0.4-0.6 mm diameter) was inserted into both sides of the tube
      through a small cut. In this new technique, there is no difficult procedure of
      retrieving the tip of a metal probe from the nasal cavity. The TPST requires no
      suture to secure it in position. The success rates were 63.6% (7/11), 100% (5/5)
      and 50% (1/2) for nasolacrimal-duct obstruction, canalicular obstruction, and
      canalicular and nasolacrimal-duct obstructions, respectively (follow-up: 3.4-12
      months, mean 5.3 months).

PMID- 8272327
TI  - [Reproducible model of a bacterial conjunctivitis].
AB  - To test the efficiency of antimicrobial substances on bacterial conjunctivitis
      under standardized conditions a reproducible model is needed. As there are no
      data in the literature concerning this topic we have developed a model of
      bacterial conjunctivitis in the rabbit eye. Instillation of a suspension of
      Haemophilus influenzae, Staphylococcus epidermidis or Staphylococcus aureus into
      the cul-de-sac did not result in any effect. Thus, standardized techniques of
      conjunctival incision were used additionally. A follow-up was done for a period
      of 2 weeks (degree of conjunctival hyperemia, microbiology). Radial incision of
      the conjunctiva with injection of an S. aureus suspension (50 microliters of ATCC
      29213; 1.35 x 10(8) cells) was done mimicking a branch injury. This resulted in a
      purulent conjunctivitis over a period of 1 week and disappeared within 14 days.
      The swabs were negative on day 7. This is the first model establishing a
      reproducible purulent conjunctivitis in the rabbit. Using this model
      antimicrobial substances may be tested under standardized conditions.

PMID- 8272328
TI  - Axial length of eyes with rhegmatogenous retinal detachment.
AB  - We conducted a prospective study of 226 eyes with nontraumatic rhegmatogenous
      retinal detachment; we examined patient characteristics as well as changes in
      axial length and corneal curvature induced by scleral buckling surgery. Eyes with
      a round hole in lattice degeneration were characterized by axial length that was
      longer than that of eyes with retinal tears with and without lattice
      degeneration. Sex and age also correlated significantly with axial length.
      Surgically induced changes in axial length depended upon the procedures
      performed, but the retinal detachment surgery primarily caused a change in the
      refractive status.

PMID- 8272329
TI  - Survival rate after vitreous surgery in patients with diabetic retinopathy.
AB  - We studied factors affecting the survival rate after vitreous surgery in 73
      patients with diabetic retinopathy, who had undergone vitreous surgery between
      1982 and 1987, according to the life-table theory and multivariate analysis. The
      5-year survival rate was 84.8%; the mean age at death was 62.1 +/- 7.1 (mean +/-
      SD) years; the mean postoperative survival time was 34.0 +/- 25.2 months; the
      most common cause of death having been cardiovascular disease, which occurred in
      5 of the 13 (38.5%) patients who had died. Patients with triopathy essentially
      require very careful systemic management, because this state was definitively
      associated with a decline in postoperative survival.

PMID- 8272330
TI  - Autosomal recessive 'optic atrophy' with late onset and evidence of ganglion cell
      dysfunction: a sibship of two females.
AB  - Two sisters aged about 40 years presented with a recent moderate reduction in
      visual acuity and pale optic discs. The nonconsanguineous parents, 7 other
      siblings and all other family members have normal vision. This strongly indicates
      a hereditary, autosomal recessive origin. A primary ganglion cell pathology is
      strongly suspected because of the significant attenuation of the early component
      of the onset/offset visual-evoked potential in the presence of little change in
      the potential to a pattern reversal stimulus.

PMID- 8272331
TI  - Long-standing follow-up electroretinographic studies after surgical resection of
      optic nerve glioma.
AB  - We followed up electrophysiological findings in 2 patients who underwent optic
      nerve glioma resection. Case 1 showed a normal flash electroretinogram (ERG) 6
      months after surgery. Case 2 showed a negative-type flash ERG and nonrecordable
      pattern ERG and flash visual-evoked cortical potentials 13 and 20 years after
      surgery. The flash ERG after surgical resection of the optic nerve was considered
      to be affected by the interruption of the central retinal artery during the
      surgery, and the preserved ERG suggested the possibility of developing the
      collateral circulation of the ciliary artery.

PMID- 8272332
TI  - Long-term corneal involvement following drug-induced toxic epidermal necrolysis
      (Lyell's disease).
AB  - Toxic epidermal necrolysis is a mucocutaneous disease that also causes important
      ocular sequelae. Conjunctival retraction, scars and sicca syndrome with severe
      corneal lesions are the principal ocular complications, sometimes resulting in a
      major handicap for the patient. We report a case where long-term sequelae ended
      in corneal perforation requiring a keratoplasty more than 20 years after the
      initial attack.

PMID- 8272333
TI  - Epidermal growth factor in the topical treatment of traumatic corneal ulcers.
AB  - The tolerability and efficacy of epidermal growth factor (EGF) in the topical
      treatment of traumatic corneal ulcers have been evaluated in a double-blind,
      placebo-controlled, randomized study in two groups of patients. The time required
      for complete reepithelialization of the cornea was recorded, and the data
      obtained were analyzed statistically. In the EGF group the reepithelialization
      was significantly faster than in the control group. Tolerability of EGF was
      always excellent. These results indicate that EGF is safe and effective in
      reducing the healing time in the management of superficial corneal lesions.

PMID- 8272334
TI  - A warm-water perfusion plaque for hyperthermic treatment of intraocular tumors.
AB  - This paper describes the design and performance of a plaque aimed at delivering
      hot-water hyperthermia to intraocular tumors. The plaque transfers heat into the
      tissues via conduction. Maximum temperature cannot exceed inflow water
      temperature. The high water flow rate provided by the hyperthermia unit
      guarantees an excessive power output at a constant temperature level, resulting
      in a homogeneous temperature distribution in the tissue. Heat distribution over
      the plaque surface was shown to be uniform. System performance has been studied
      on enucleated human as well as on living rabbit eyes. Thermal mapping was done in
      two and one planes, respectively, and the spatial distribution was calculated.
      Results promise therapeutic temperature levels to a depth exceeding 10 mm.

PMID- 8272335
TI  - Dual immunologic property of S-100 protein in normal eyes and eyes with
      retinoblastoma: a histopathological and immunohistochemical study of 88 cases.
AB  - To ascertain the cell types expressing S-100 protein in eyes with retinoblastoma,
      a follow-up study was made on 88 formalin-fixed and paraffin-embedded
      retinoblastoma specimens histopathologically and immunohistochemically, using
      antibodies against S-100 protein. In normal retinas and morphologically normal
      retinas with retinoblastoma, both astrocytes and ganglion cells were stained
      positively for S-100 protein. In the retinoblastomas, not only the reactive
      astrocytes in most cases, but also large tumor cells with large cell bodies,
      prominent nucleoli and well-differentiated figures were positive for S-100
      proteins in 2 cases. These large tumor cells were thought to be neuronal and were
      called ganglion-like cells because they were morphologically and
      immunohistochemically compatible with the large ganglion cells in normal retina.
      The results indicate that in eyes with retinoblastoma, S-100 protein has both
      neuronal and glial immunologic properties and could have a limited value as a
      glial marker for the histogenesis study of retinoblastoma.

PMID- 8272336
TI  - Magnetic resonance imaging features of congenital anophthalmia.
AB  - Congenital anophthalmia (CA) is a rare malformation. Primary forms without
      development of optic nerves can be differentiated from secondary forms with
      rudimentary optic nerves and eye bulbi. Neuroradiologic examinations in these
      children are performed to differentiate primary from secondary forms and to
      exclude associated cerebral malformations. We report on 2 children with secondary
      CA, a 9-month-old girl with unilateral CA and a 3-year-old boy with bilateral CA.
      Magnetic resonance imaging (MRI) was superior to computerized tomography (CT) in
      the delineation of the rudimentary optic nerves and tracts as well as the
      intraorbital contents. In addition magnetic resonance images revealed partial
      agenesis of the corpus callosum and microgyria of the calcarine cortex in the
      boy. These results suggest that MRI should replace CT in the diagnosis of CA.

PMID- 8272337
TI  - Convergence paralysis after lesions of the cerebellar peduncles.
AB  - We studied vergence eye movements in a patient with limited hemorrhage affecting
      the right cerebellar peduncles and the hemisphere. The patient showed exotropia
      of 30 prism dptr during near vision. Some vergence paradigms were investigated in
      this patient. We studied fusional vergence evoked by placing a wedge prism before
      one eye. Accommodative vergence was studied by blur stimulus using a
      servocontrolled optometer. Lens accommodation was also recorded during blur
      stimulus. Although accommodative responses were normal, accommodative vergence
      was almost absent as well as fusional convergence in this patient. It has
      previously been reported that the cerebellum has a role in the control of
      vergence in the monkey. Our data suggest that the human cerebellum also relates
      to the control of vergence.

PMID- 8272338
TI  - Effects of iodate on intraretinal b and c waves of the cat electroretinogram.
AB  - In 12 cats, the intravenous and intravitreal administrations of sodium iodate
      (SI) were performed to examine the effects on b and c waves of electroretinogram
      in the dark-adapted retina. The intravitreal SI (0.5-3.5 mM) produced the
      complete suppression of intraretinal b waves without remarkable changes of slow
      PIII and light-evoked [K+]o decrease in the subretinal space. Intravenous SI (30
      mg/kg) also showed the suppression of intraretinal b waves. SI not only acted as
      a poison to the retinal pigment epithelium but also might block the post-synaptic
      response.

PMID- 8272339
TI  - Cardiovascular reflex testing and pupil cycle time in open-angle glaucoma.
AB  - The aim of the study is to assess the value of function tests of the autonomic
      nervous system in open-angle glaucoma by testing the cardiovascular reflexes and
      pupil cycle time. The experimental group consisted of 19 glaucoma subjects with
      controlled intraocular pressure. The control group consisted of 20 healthy
      volunteers. The Valsalva test has proven to be considerably accurate in the
      assertion of autonomic dysfunction (p < 0.05). Pupil cycle time was significantly
      prolonged (p < 0.001). These results confirm the role of autonomic dysfunction in
      open-angle glaucoma.

PMID- 8272340
TI  - Conjunctival malignant melanoma with xeroderma pigmentosum.
AB  - A 10-year-old male patient with xeroderma pigmentosum had a recurrent, pigmented,
      conjunctival tumor. Conjunctival malignant melanoma was diagnosed from the
      histopathological examination of the resected biopsy specimens. To our knowledge,
      this case of conjunctival malignant melanoma in a patient with xeroderma
      pigmentosum may be the second such report in the literature. We believe that
      malignant melanoma must be considered with squamous cell carcinoma in the
      differential diagnosis of conjunctival tumors in patients with xeroderma
      pigmentosum. Fontana-Masson and S-100 staining techniques helped diagnose this
      conjunctival malignant melanoma.

PMID- 8272341
TI  - Contrast sensitivity for the stationary and drifting vertical stripe patterns in
      patients with optic nerve disorders.
AB  - Subjective contrast sensitivity for the stationary and horizontally drifting
      vertical stripe patterns was measured in normal subjects and in patients with
      glaucoma, optic neuritis and optic atrophy. Contrast sensitivity was also
      determined objectively using an eye movement reflex (optokinetic nystagmus)
      recorded by means of electro-oculography. The contrast sensitivity for the
      drifting stripe patterns in normal subjects was characterized by a depression of
      sensitivity at the high spatial frequency and an increased contrast sensitivity
      at the low spatial frequency in comparison with the results of stationary stripe
      patterns. The measurement of contrast sensitivity for the horizontally drifting
      vertical stripe patterns was found to be more sensitive for detection of minor
      damage to the optic nerve than that for the stationary patterns. The results of
      the subjective contrast sensitivity and the objective one determined using an eye
      movement reflex showed a good correlation.

PMID- 8272342
TI  - Evolution of angioid streaks.
AB  - Angioid streaks of the fundus are not apparent at birth. In order to study their
      evolution, we examined in a retrospective manner the fundus pictures of 111
      subjects with angioid streaks. The earliest form of angioid streaks became
      apparent at age 8 with findings of narrow short radial discontinuous
      hypopigmented streaks. Thereafter angioid streaks enlarged in length and width.
      The end-stage was disciform macular degeneration, helicoid peripapillary atrophy,
      or diffuse choroidal sclerosis with obscuration of the angioid streaks. We
      conclude that angioid streaks represent a dynamic manifestation of an underlying
      retinochoroidal degenerative process.

PMID- 8272343
TI  - Retinal telangiectasis and proliferation of the retinal vessels in a family.
AB  - A 20-year-old woman presented with a marked proliferative retinopathy of the
      entire central region of the retina in both eyes, with veil-like epiretinal
      gliovascular membranes and isolated spots of haemorrhaging. The outer region of
      the retina was unremarkable. Her 49-year-old mother showed perimacular
      telangiectases in both eyes. The vascular system of both patients were medically
      sound, and, in particular, the blood pressure, blood sugar and blood picture were
      normal, with no signs of heart, kidney, lung or liver disease. The first patient
      had been a heavy smoker for 6 months, and the second did not smoke. The 84-year
      old mother of the second patient was blind following bilateral Horton's temporal
      arteritis.

PMID- 8272344
TI  - Topical immunoglobulins for epithelial herpes simplex keratitis.
AB  - A new immunoglobulin preparation for topical administration in the eye has been
      developed. The tolerance to this preparation was tested in a phase I/II study, in
      combination with the antiviral drug trifluorothymidine, in 5 patients with
      untreated episodes of herpes simplex epithelial keratitis. The clinical course of
      these patients was within usual limits, with a mean healing time of 6.6 days
      (range 2-15 days). No undesirable effects were observed. Our findings suggest
      that this new treatment modality is safe and offers a new perspective, but
      additional studies are required to determine its efficacy.

PMID- 8272345
TI  - Analytical and statistical survey of early stages of open-angle glaucoma with low
      luminance visual field.
AB  - The purpose of this study was to show the early visual field signs in glaucoma
      using the 'Moniteur Ophtalmologique' at a background mesopic luminance of 0.3
      apostilbs. Forty-five patients were selected, and 68 eyes with suspected early
      glaucoma were examined. Among the defects which were studied, we noticed a
      predominance of what we called pericaecal scotoma (PCS) and levelling. These two
      first signs appear as an alarm signal. To detect the early visual field signs of
      open-angle glaucoma developing, this study recommends the use of a background
      mesopic luminance of 0.3 apostilbs and observation for two uncommon visual field
      signs: PCS in evolution around the blind spot and a slight decrease in central
      mesopic sensitivity called levelling.

PMID- 8272346
TI  - Use of argon laser photocoagulation in the treatment of recurrent trichiasis:
      long-term results.
AB  - We describe our technique and analyze the long-term results of the use of argon
      laser photocoagulation in the treatment of 92 eyes with recurrent trichiasis. In
      spite of an incidence of recurrences of 64.1% which had to undergo a new laser
      photocoagulation session, the final success rate of the method was impressive
      (91.3%). The number of misdirected cilia per lid seems to constitute an important
      factor which affects both the rate of recurrences and the success rate of the
      procedure.

PMID- 8272347
TI  - Temporal modulation transfer function of vision by pattern visual evoked
      potentials in patients with optic neuritis.
AB  - To reveal the impairment of the temporal modulation transfer function of vision
      in patients with optic neuritis, the pattern visual evoked potentials (P-VEPs)
      were recorded at reversal frequencies ranging from 4 to 24 per second, and the
      fast Fourier transform (FFT) of VEPs were investigated. In normal subjects,
      curves of the square root of the power of the FFTs of P-VEPs versus temporal
      frequency showed the maximum peak at 6 Hz (12 reversals/s). The specific
      distribution of the power spectrum could be found at each temporal frequency, and
      the amplitudes of higher harmonic components decreased while a single power
      spectrum peak became prominent as the temporal frequency increased. In patients
      with optic neuritis, an abnormality of the power spectrum of steady-state P-VEPs
      could by detected by estimating the 1st and 2nd harmonic components. The
      abnormality of the power spectrum of transient P-VEPs could be detected by
      estimating the higher harmonic components of the power spectrum.

PMID- 8272348
TI  - Oral manifestations of HIV infections.

PMID- 8272350
TI  - Oral medicine: is it special?

PMID- 8272349
TI  - Immediate placement of dental implants into extraction sockets: surgically
      related difficulties.
AB  - Osseointegrated dental implants have proven predictably successful when
      appropriate guidelines are followed. The Branemark Technique includes a period of
      up to 12 months for post-extraction bone healing. This delay, combined with the
      inevitable ridge resorption following extraction may contribute to several
      problems. The two common difficulties are: insufficient available bone for ideal
      implant placement and, prolonged treatment time. Recently several investigators
      have reported on the immediate placement of osseointegrated dental implants into
      extraction sockets. This technique was developed in order to eliminate or
      minimize the problems associated with delayed implant placement. Readers are
      referred to: Oral Health, pg. 19, July 1992, which discusses the technique and
      advantages of immediate placement of dental implants into extraction sockets.
      This paper discusses some of the difficulties associated with immediate implant
      placement. Several types of complications that may occur are summarized in Table
      I and expanded in the text of the article.

PMID- 8272351
TI  - [C-peptide levels in secondary sulfonylurea resistant diabetics].
AB  - In the presence of clinical features of secondary drug failure--even after
      reeducation on diet and intensive control of patients--is difficult to make a
      decision to switch on insulin. Therefore the serum C-peptide concentrations were
      assessed in order to get supporting data. From 35 patients with suspected
      secondary drug failure the therapy of 11 patients was continued with insulin, 24
      patients remained on glibenclamide therapy. The decision based on clinical
      criteria. All of the patients were studied in i.v. glucagon test and with a test
      meal to evaluate their basal and stimulated serum C-peptide concentrations. There
      were only three patients with subnormal basal C-peptide (< or = 0.30 nmol/l), on
      the other hand nine patients had lower post-glucagon serum C-peptide level than
      0.60 nmol/l. The basal and stimulated C-peptide concentrations from i.v. glucagon
      test and test-meal indicated the need of insulin therapy with a sensitivity of
      81.8 percent and with specificity of 70.8 percent. The further glibenclamide
      treatment on the basis of C-peptide concentrations in 89.5 percent of cases could
      be accurately established. The statistical analysis showed that the glucagon
      stimulated C-peptide concentration was the most characteristic feature to
      discriminate the patients in order to make a decision on the further diabetes
      therapy.

PMID- 8272352
TI  - [Complications from physiological and rate responsive pacemaker implantations].
AB  - One hundred eighteen surgical complications of 209 patients underwent 249
      physiological and rate responsive pacemaker implantations are discussed. In 27.9%
      of total complications represented the dislodgement of atrial leads occurred
      particularly in the early period of the observation time which decreased
      significantly later in the second period of the survey. This high complication
      rate of bifocal pacemakers was found due to a high incidence of the generator
      preerosion beside the dislodgment of the atrial electrodes. Complication rate
      could be reduced by the improvement of surgical technics, and with the
      implantations of new types of leads and smaller generators, however the number of
      complications remained higher compared to the pacemaker systems with one lead.
      The implantation procedure of ventricular rate responsive pacemakers is simple,
      and significant improvement in working capacity could be observed by the
      restoration of the chronotropic capacity during exercise. Physiological and
      atrial rate responsive pacemakers provide many advantages in the hemodynamic
      state even at rest which exceed all disadvantage of the expected complications,
      which might occur.

PMID- 8272353
TI  - [Importance of abnormal fetal presentation of twins during labor and delivery].
AB  - Utilizing the 18 year material of two institutions, the author investigated the
      effect of fetal lie and presentation on the labor and delivery process. Out of
      541 pairs of twins, in 299 instances (55.27%) at least one of the fetuses
      occupied a transverse lie or presented by the breech. In the remaining 242 pairs
      (44.73%), both fetuses presented by the vertex. In association with premature
      labor, out of 239 sets of twins, in 134 instances (56.07%), the presentation of
      at least one of the twins was abnormal. The same phenomenon occurred in 165 out
      of 302 pairs (54.63%) when labor set in at term. The percentual frequency of
      abnormal presentations appeared to be positively related to maternal age and
      parity. In connection with abnormal presentations, there was an increase in the
      rate of cesarean sections (38.13% versus 13.21%) and that of low Apgar scores
      (18.18% versus 9.3%), as compared to those cases where both fetuses presented by
      the vertex. Of all cases of perinatal mortality, 57.76% involved twin pairs with
      abnormal presentation versus 42.24% for cases where both fetuses presented by the
      vertex.

PMID- 8272355
TI  - [Present status and future plans of the Scientific Public Health Council].

PMID- 8272354
TI  - [Poly-electrolyte fractionated porcine factor VIII in the treatment of hemophilia
      A].
AB  - In approximately 10 to 15 percent of congenital hemophilia A patients circulating
      antibodies to factor VIII appear in the blood that poses a serious problem in
      their treatment. A number of methods and preparations are used in the clinical
      practice to overcome this problem. Authors report their favourable clinical
      experience with the administration of polyelectrolyte-fractionated porcine factor
      VIII. concentrate in a hemophiliac child for the first time in Hungary and a
      brief review of the clinical methods in use in the management of factor VIII.
      inhibitors.

PMID- 8272356
TI  - [Jozsef Lenhossek on macrocephaly].

PMID- 8272358
TI  - Alternative scheme proposed for CCB drugs.

PMID- 8272357
TI  - [Beginning of the usage of the national language in the 16th century work "Ars
      Medica"].

PMID- 8272359
TI  - 1993 Distinguished Service Award: a warm, pioneering heart.

PMID- 8272360
TI  - Finding the best response: hospital affiliations.

PMID- 8272361
TI  - How to help your patients avoid food poisoning.

PMID- 8272362
TI  - Nutrition should be preventive medicine for older adults.

PMID- 8272363
TI  - Medicare offering hospice coverage.

PMID- 8272364
TI  - Congress tightens limits on self-referrals under Medicare and Medicaid. The
      Health Care Group.

PMID- 8272365
TI  - If you care about your patients...

PMID- 8272366
TI  - Synergistic activation of non-rectifying small-conductance chloride channels by
      forskolin and phorbol esters in cell-attached patches of the human colon
      carcinoma cell line HT-29cl.19A.
AB  - Cell-attached patch-clamp studies with the human colon carcinoma HT-29cl.19A
      cells revealed a small chloride channel with a unitary conductance of 6.5 pS at
      70 mV and 4.6 pS at -70 mV clamp potential after cAMP was increased by activation
      of adenylyl cyclase by forskolin. Usually channels inactivated upon patch
      excision, but in a few excised patches the channels stayed active and displayed a
      linear I/V relation in symmetrical (150 mmol/l) chloride solutions with a
      conductance of 7.5 pS. A 16-fold increase in channel incidence was observed when
      forskolin and phorbol 12,13-dibutyrate (PDB) were present together. The open
      probability was voltage-independent and was not different in the presence of
      forskolin plus PDB or with forskolin alone. The conductance sequence of the
      channel as deduced from outward currents carried by five different anions
      including chloride was: Cl- > BR- > NO3- > gluconate > I-. The permeability
      sequence deduced from the reversal potentials was NO3- > or = Br- > Cl- > I- >
      gluconate. With iodide in the pipette the conductance decreased strongly.
      Moreover, the inward current was reduced by 61%, indicating a strong inhibition
      of the chloride efflux by iodide. Similarly, the forskolin-induced increase of
      the short-circuit current (Isc) in confluent filter-grown monolayers was strongly
      reduced by iodide in the apical perfusate. Iodide also increased the fractional
      resistance of the apical membrane and repolarized the membrane potential,
      indicating an inhibitory action on the forskolin-induced increase of the apical
      chloride conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272367
TI  - Cholinergic responses in cloned human TE671/RD tumour cells.
AB  - The cholinergic responses of the human tumour cell line TE671/RD were examined
      using digital Ca2+ imaging fluorescence microscopy and patch-clamp measurements.
      In response to stimulation of the muscarinic acetylcholine (ACh) receptor
      (mAChR), the intracellular concentration of Ca2+ ([Ca2+]i) rose about two-fold,
      in parallel with inositol 1,4,5-trisphosphate accumulation, measured by
      chromatographic techniques. By contrast, there was no increment of [Ca2+]i upon
      stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine
      application. Electrophysiological experiments showed that TE671/RD cells lack
      functional voltage-activated Ca2+ channels. The stimulation of the nAChR induced
      transient whole-cell currents (IACh). Little or no current was detected in
      isotonic extracellular Ca2+, with Cs+ in the patch pipette. Cell pretreatment
      with muscarine reduced IACh by about 20%, without consistent modifications of
      current kinetics. Muscarine applied to the extra-patch membrane under the cell
      attached configuration had no obvious effect on ACh-evoked unitary events. In
      conclusion, in human TE671/RD cells, muscarinic stimulation increases [Ca2+]i,
      while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar
      ion permeability properties and is not functionally regulated by the breakdown of
      phosphoinositides.

PMID- 8272368
TI  - Protein kinase C as mediator of arachidonic acid-induced decrease of neuronal M
      current.
AB  - The M current, IM, of NG108-15 neuroblastoma x glioma hybrid cells, a non
      inactivating K+ current, is decreased by arachidonic acid (5-25 microM), often
      after an initial transitory increase. To test the possibility that the decrease
      is caused by activation of protein kinase C (PKC) we used the PKC 19-31 peptide,
      which is an effective inhibitor of PKC. With 1 microM peptide in the pipette
      solution the normally observed strong reduction of IM by 1 microM phorbol 12,13
      dibutyrate (PDB) was almost totally prevented, indicating that PKC is completely
      inhibited; also the voltage dependence of the M conductance, gM(V), was shifted
      to more negative membrane potentials. In the presence of 1 microM peptide the
      effect of 25 microM arachidonic acid on IM was significantly reduced, suggesting
      that the effect, or at least a large part of it, is mediated by PKC.

PMID- 8272369
TI  - Latency in the inositol lipid transduction pathway: the role of cellular events
      in responses to thyrotropin-releasing hormone in Xenopus oocytes.
AB  - To dissect the cellular events responsible for the prolonged latency of the
      response to thyrotropin-releasing hormone (TRH) in Xenopus oocytes we interfered
      with different steps of the signal transduction pathway. Preincubation of oocytes
      with cis-vaccenic acid (a membrane-fluidizing agent) shortened the latency,
      suggesting a contribution of membranal processes. TRH-induced depletion of
      cellular calcium stores prolonged latency (up to threefold), which returned to
      control levels upon repletion of the stores. Injection of D-2,3
      diphosphoglycerate (PGA), which inhibits inositol (1,4,5)-trisphosphate (InsP3)
      dephosphorylation, alone evoked a small, prolonged depolarizing current and
      significantly shortened the latency of the response to TRH. Injection of
      guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), which inactivates guanine
      nucleotide-binding regulatory proteins, decreased the amplitude of the response
      and increased latency. Injection of guanosine 5-O-(3-thiotriphosphate) (GTP gamma
      S) immediately before the challenge with TRH did not shorten the latency of the
      response. Decreasing the effective receptor density with chlordiazepoxide, an
      antagonist of the TRH receptor, resulted in an extension of latency, whereas the
      expression of a large number of TRH receptors by injection of RNA transcribed
      from cloned receptor DNA (10-100 ng/oocyte) shortened the latency to below 2 s.
      Our results suggest that the latency of the response to TRH reflects the
      activation of a late step in the signal transduction sequence, most likely the
      release of calcium by InsP3. We propose that this process is kinetically
      controlled by an early rate-limiting event, involving the activation of a guanine
      nucleotide-binding protein by the TRH receptor.

PMID- 8272370
TI  - Changes of tension and [Ca2+]i during beta-adrenoceptor activation of single,
      intact fibres from mouse skeletal muscle.
AB  - beta-Adrenergic agonists increase tension production in fast-twitch skeletal
      muscle, but the underlying mechanism is unknown. In the present study we have
      exposed intact, single fibres from a mouse muscle to the beta 2-adrenergic
      agonist terbutaline. Fibres were stimulated to produce 350-ms tetani at 20-100 Hz
      while measuring the myoplasmic Ca2+ concentration ([Ca2+]i) and tension. The
      fluorescent indicator Indo-1 was used to measure [Ca2+]i. Application of
      terbutaline resulted in marked increases of both tetanic [Ca2+]i and tension.
      Terbutaline had no significant effect on myofibrillar function as judged from
      normal Ca2+ sensitivity and tension production at saturating [Ca2+]i. The rate of
      [Ca2+]i and tension decline during relaxation was not affected by terbutaline,
      thus indicating a normal function of the sarcoplasmic reticulum (SR) Ca2+ pumps.
      The effect of terbutaline developed gradually over 5-10 min when fibres were
      stimulated each minute; the full effect of terbutaline was also obtained after a
      10-min rest period in terbutaline. The [Ca2+]i at rest was not affected by
      terbutaline. In conclusion, beta-adrenergic stimulation increases tetanic tension
      by enhancing SR Ca2+ release.

PMID- 8272372
TI  - Intrapulmonary gas mixing and pulmonary gas exchange in artificially ventilated
      dogs.
AB  - To investigate the effect of incomplete gas mixing between tidal air and residual
      gas on pulmonary gas exchange, anaesthetized dogs were ventilated artificially
      with breathing patterns with different durations of the post-inspiratory apnoea
      (ta = 0, 0.5, 1.0 and 2.0 s), where tidal volume, breathing frequency,
      inspiratory and expiratory flow patterns were kept constant. We determined the
      alveolar ventilations (VA) of He and SF6 from the product of end-expiratory lung
      volume (VL,E') and specific ventilation (VA/VL,E'). VL,E' was determined by the
      dilution technique and the specific ventilations of the two gases were obtained
      from their multiple-breath washout. Further, tracer amounts of acetone, ether and
      enflurane were infused continuously into a peripheral vein and a bolus of a gas
      mixture of krypton, Freon12 and SF6 was introduced into the peritoneal cavity. We
      determined the Excretion (E) and Retention (R) of these six gases according to
      the multiple-inert-gas-elimination technique (MIGET). VA increased with
      increasing ta, where VA,He was about 14% larger than VA,SF6. For both gases,
      however, the increase in VA relative to control (VA for ta = 0) was virtually the
      same: 9, 11 and 19% (mean values) for ta = 0.5, 1.0 and 2.0 s respectively. For
      all dogs the E/R curve shifted to larger E values with increasing ta. E for the
      most soluble tracer gas (acetone) increased by 11, 21 and 25% for ta = 0.5, 1.0
      and 2.0 s respectively. VA, determined with MIGET from the ventilation/perfusion
      distribution, increased by almost the same percentages.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8272371
TI  - Endothelin and vasopressin activate low conductance chloride channels in aortic
      smooth muscle cells.
AB  - The non-contractile aortic smooth muscle cell line A7r5 was used to study the
      membrane events involved in the effect of vasoconstrictor peptides. Whole-cell
      voltage-clamp and membrane potential recording techniques were used to
      demonstrate the contribution of an increased Cl- conductance to the late
      depolarization induced by endothelin-1 and vasopressin. During cell-attached
      patch recording with N-methyl-D-glucamine in the pipette, bath application of
      endothelin or vasopressin induced single-channel inward currents in the following
      minutes. The current/potential (I/V) curve of the most frequently observed
      channel type--a small conductance Cl- (SCl) channel--reversed near the cell
      membrane potential and showed a single-channel conductance of 1.8 pS for inward
      currents. After patch excision in an extracellular solution containing CaCl2 (2
      mM), the frequency of SCl channel openings increased. Patch excision in the
      absence of peptide stimulation also produced this channel activity. Replacement
      of CaCl2 by a Ca2+ chelator on the intracellular face of a patch reversibly
      inhibited the channel activity, indicating that these SCl channels are Ca(2+)
      activated Cl- channels. The single-channel I/V characteristic showed outward
      rectification above +50 mV. An analysis of the gating kinetics of the SCl channel
      is given. Another channel type was recorded less frequently after peptide
      stimulation. It had a lower conductance (1.0-1.3 pS) and slower kinetics and was
      designated a very small conductance Cl- channel. It is concluded that activation
      of two types of Cl- channels (at least one of which is Ca2+ dependent) is
      involved in the late depolarization produced by vasoconstrictor peptides in
      vascular smooth muscle cells of the aortic cell line A7r5.

PMID- 8272373
TI  - An automatic monitoring system for epithelial cell height.
AB  - This paper describes an automatic method to measure cell height (h) of epithelia
      grown as monolayers on transparent filter supports. Tissues are mounted in an
      Ussing-type chamber enabling solution exchange on both sides. The apical and
      basal side of the epithelial cells are marked with fluorescent beads. The image
      of the fluospheres is captured with a video camera and processed by a computer
      based video imaging system. One basal reference bead in a gelatin layer on the
      filter support and up to three beads attached at the apical surface are used to
      monitor changes in cell height of three cells simultaneously. The focusing of the
      microbeads is done automatically by moving the objective with a piezoelectric
      device mounted on the nosepiece of the microscope. The algorithm for locating the
      bead is based on the changes in fluorescent light intensity emitted by the
      fluospheres. The method has an accuracy higher than 0.1 micron and a time
      resolution as low as 6 s if measurements are restricted to one bead at the apical
      side. The method was tested on artificial model systems and used to measure
      volume changes in renal cultured epithelia (A6) after exposing the serosal
      surface to hypotonic solutions and replacing cell-impermeable sucrose by an
      organic compound (glycerol) with a smaller reflection coefficient. Serosal
      hypotonicity elicited a rapid volume increase followed by regulatory volume
      decrease, whereas the organic compound replacement caused a steady increase in
      cell volume.

PMID- 8272374
TI  - A new approach to separation of voltage-activated Ca currents in rat
      melanotrophs.
AB  - The whole cell patch clamp technique was used to study voltage-activated calcium
      currents in rat melanotrophs. Voltage ramps of the same amplitude and of
      different durations were applied to separate Ca currents with different
      electrophysiological properties. The application of those with voltage gradient
      of 0.5 V/s resulted in a clear separation of two inward current components,
      activated at -55 +/- 5 mV and -24 +/- 5 mV respectively, corresponding to low
      (LVA) and high (HVA) voltage-activated currents. The proportion of cells
      displaying such current separation was reduced either at voltage gradients of
      0.053 V/s or 1.6 V/s. The application of nitrendipine and nicardipine resulted in
      a blockage of both currents, where the HVA current component was more sensitive
      to the agents. The sensitivity of both Ca currents to dihydropyridine antagonists
      suggests that these currents may be mediated by subtypes of a dihydropyridine
      sensitive Ca channel.

PMID- 8272375
TI  - The effect of EMD 57033, a novel cardiotonic agent, on the relaxation of skinned
      cardiac and skeletal muscle produced by photolysis of diazo-2, a caged calcium
      chelator.
AB  - EMD 57033 is thought to produce its potentiating effect by increasing the
      apparent calcium sensitivity of myofibrils. We have investigated the effect of 10
      microM EMD 57033 on relaxation speed, induced by flash photolysis of 2mM diazo-2
      (a caged Ca2+ chelator), in skinned semitendinosus frog muscle fibres and guinea
      pig trabeculae. 10 microM EMD 57033 has no effect on the relaxation speed of
      semitendinosus fibres. In trabeculae, EMD 57033 slightly increases the relaxation
      speed slightly, in contrast to ADP which produces a slowing. 1mM ADP combined
      with 10 microM EMD 57033 slows relaxation but not to the degree seen with ADP
      alone. Like ADP, EMD 57033 increases the number of cross-bridges in the force
      producing state, but unlike ADP does not affect the transition rates involved in
      relaxation.

PMID- 8272376
TI  - Transepithelial dipeptide (glycylsarcosine) transport across epithelial
      monolayers of human Caco-2 cells is rheogenic.
AB  - Net transepithelial transport (and cellular accumulation) of the dipeptide
      glycylsarcosine (Gly-Sar), across the apical membrane of human intestinal Caco-2
      epithelia, is driven by a proton gradient (Na(+)-free conditions) and displays
      saturation kinetics (Km 17.4 +/- 5.1 mM, Vmax of 92.8 +/- 15.6 nmol.cm-2.h-1).
      Net Gly-Sar transport is associated with the stimulation of an inward short
      circuit current (Isc). This dipeptide-stimulated Isc is observed in both Na(+)
      containing and Na(+)-free conditions, is stimulated by apical acidity, and
      displays saturation kinetics (in Na(+)-free media at apical pH 6.0, Km of 13.6 +/
      4.5 mM and a Vmax of 284.1 +/- 39.3 nmol.cm-2.h-1). The maximal capacities of
      Gly-Sar transport and Isc suggest a dipeptide/proton stoichiometry greater than
      unity (1:3).

PMID- 8272377
TI  - Factors affecting the propagation of locally activated systolic Ca transients in
      rat ventricular myocytes.
AB  - A method is described to activate the systolic rise of [Ca2+]i in only one region
      of a single, isolated cell. This is achieved by applying the calcium chelator
      BAPTA to the rest of the cell from a pipette. Under control conditions electrical
      stimulation produced a Ca transient which was uniform throughout the cell. If a
      BAPTA containing solution was applied to one region of the cell for 100-500 ms
      before stimulation then there was no systolic Ca transient in that region of the
      cell. In the rest of the cell, however, the Ca transient was identical to that in
      control conditions. If BAPTA application was discontinued the Ca transient was
      normal throughout the cell on the next stimulation. In the presence of ouabain
      the locally activated systolic Ca transient propagated through the cell.
      Propagation was associated with an increase of systolic but not diastolic
      [Ca2+]i. These results show that the systolic Ca transient propagates if the cell
      Ca content is elevated. We suggest that the fact that Ca-overload produces
      spontaneous Ca release may be due to the fact that it allows spontaneous Ca
      release (which may always be occurring) to propagate.

PMID- 8272378
TI  - A slowly inactivating transient outward current in rat ventricular myocytes.
AB  - In rat ventricular myocytes we found two components of transient outward current,
      which could be discriminated time- and voltage- dependently. Besides the well
      known fastly inactivating transient outward current (ito,f, tau = 35 +/- 8 ms, n
      = 4) we investigated properties of a slowly inactivating transient outward
      current (ito,s, tau = 1.7 +/- 0.4 s, n = 4). Because of the slow inactivation
      process of ito,s tail currents were observed at -25 mV. The inactivation curve of
      ito,f was characterized by a half- inactivation voltage of -58.4 +/- 1.4 mV and a
      slope factor of 5.6 +/- 0.5 mV (n = 4). The inactivation curves of ito,s and tail
      currents were nearly identical but significantly different from the ito,f-curve.
      Half-inactivation voltages of ito,s and tail currents were -87.5 +/- 6 mV and 
      89.1 +/- 5 mV (n = 4), respectively. Slope factors were 10.3 +/- 2.9 mV and 9.8
      +/- 1.7 mV (n = 4). The activation gate of ito,s was half-maximally opened at 
      11.5 +/- 2.6 mV, and the slope factor was -10.6 +/- 1.7 mV (n = 3). Ito,s tail
      current reversed its direction at -62 +/- 3.2 mV (n = 5). This indicates, that
      ito,s- current flow is carried mainly by potassium ions. Ito,s- current was not
      abolished by Tetrodotoxin (TTX) and Cd.

PMID- 8272379
TI  - Spike generating smooth muscle cells in mesenteric artery of rats.
AB  - Membrane electrical properties of smooth muscle cells at different loci in the
      vessel wall of rat small mesenteric arteries were studied using glass
      microelectrodes. Isometric force was measured simultaneously. Penetrations of
      smooth muscle cells on the adventitial side (outer cells) showed an average
      resting potential, -43.1 +/- 0.8 mV (n = 24). In outer cells, numerous
      depolarizing junctional potentials and, to a lesser degree, hyperpolarizing
      junctional potentials were observed. When current was injected, electrotonic
      potentials were recorded. Input resistance was 2.2 +/- 0.1 x 10(9) omega (n =
      15), suggesting that the low resistance pathways commonly observed in smooth
      muscle tissue are absent among these cells. Transmural electrical stimulation of
      nerves elicited spikes and summation of junctional potentials, accompanied by
      force. TTX virtually abolished these effects of the transmural stimulation. In
      contrast, cells near the intima (inner cells) had an average resting potential of
      -65.8 +/- 0.9 mV (n = 37). No spontaneous electrical activity was observed; nor
      could electrotonic potentials be recorded. Thus, the smooth muscle cells from the
      outer layer of rat small resistance arteries differ from the inner cells in their
      lower membrane potentials, generation of spikes, higher input resistance and
      innervation. Results also suggest that the influence of nerves may be to
      facilitate opening of voltage-gated Ca2+ channels in innervated cells.

PMID- 8272380
TI  - Effects of acidic stimuli on intracellular calcium in isolated type I cells of
      the neonatal rat carotid body.
AB  - We have investigated the effects of acidic stimuli upon [Ca2+]i in isolated
      carotid body type I cells from the neonatal rat using indo-1 (AM-loaded). Under
      normocapnic, non-hypoxic conditions (23 mM HCO3-, 5% CO2 in air, pHo = 7.4), the
      mean [Ca2+]i for single cells was 102 +/- 5.0 nM (SEM, n = 55) with 58% of cells
      showing sporadic [Ca2+]i fluctuations. A hypercapnic acidosis (increase in CO2 to
      10%-20% at constant HCO3-, pHo 7.15-6.85), an isohydric hypercapnia (increase in
      CO2 to 10% at constant pHo = 7.4) and an isocapnic acidosis (pHo = 7.0, constant
      CO2) all increased [Ca2+]i in single cells and cell clusters. The averaged
      [Ca2+]i response to both hypercapnic acidosis and isohydric hypercapnia displayed
      a rapid rise followed by a secondary decline. The averaged [Ca2+]i response to
      isocapnic acidosis displayed a slower rise and little secondary decline. The rise
      of [Ca2+]i in response to all the above stimuli can be attributed to no single
      factor other than to a fall of pHi. The hypercapnia-induced rise of [Ca2+]i was
      almost completely abolished in Ca(2+)-free solution, suggesting a role for Ca2+
      influx in triggering and/or sustaining the [Ca2+]i response. These results are
      consistent with a role for type I cell [Ca2+]i in mediating pH/PCO2
      chemoreception.

PMID- 8272381
TI  - Anion exchange in type II pneumocytes freshly isolated from adult guinea-pig
      lung.
AB  - We have studied chloride influx and efflux in a highly purified preparation of
      type II cells freshly isolated from adult guinea-pig lung using 36Cl-. Chloride
      uptake was time-dependent, saturable (Km < 10 mM) and was inhibited by 4,4'
      diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS; Ki approximately 80
      microM). In the absence of external chloride (substituted by gluconate), 36Cl-
      uptake exhibited an overshoot above equilibrium. The rate of 36Cl- entry was
      strongly inhibited by addition of external nitrate; sulphate was a weaker
      inhibitor. 36Cl- efflux was stimulated by external bromide > bicarbonate > or =
      chloride > or = citrate; and was inhibited by propionate > acetate > oxalate.
      Although the "chloride channel blocker" 4-nitro-2-(3-phenylpropylamino)benzoate
      (0.14 mM) caused an inhibition, 36Cl- influx did not appear to be electrogenic.
      These data are compatible with the existence of a substantial electroneutral
      anion-exchange pathway for chloride transport in freshly isolated adult type II
      pneumocytes.

PMID- 8272382
TI  - Na/H exchange activities in NHE1-transfected OK-cells: cell polarity and
      regulation.
AB  - The human fibroblast, "amiloride-sensitive" Na/H exchanger (NHE1) was transfected
      into opossum kidney cells (OK cells) (OK/NHE1 cells). Northern blot analysis
      confirmed that the NHE1 message is expressed in OK/NHE1 cells. In immunoblot
      analysis, an anti-human NHE1 antibody labelled a membrane protein only present in
      OK/NHE1 cells. In contrast to the parental cell line containing only an apically
      located, "amiloride-resistant" Na/H exchange activity, OK/NHE1 cells contain
      apically and basolaterally located Na/H exchange activities, the apical activity
      being "amiloride resistant" and the basolateral being "amiloride sensitive".
      Parathyroid hormone (PTH) inhibited apical transport activity (OK and OK/NHE1
      cells) but had no effect on basolateral transport activity (OK/NHE1 cells).
      Pharmacological activation of protein kinase A (forskolin) decreased both apical
      and basolateral Na/H exchange activity. Incubation with phorbol ester (exogenous
      activation of protein kinase C) reduced apical Na/H exchange activity (OK and
      OK/NHE1 cells) but had only a moderate, inhibitory effect on basolateral Na/H
      exchange activity (OK/NHE1 cells). These results indicate that transfection of OK
      cells with human fibroblast NHE1 cDNA encoding an "amiloride-sensitive" form of
      the Na/H exchanger results in expression of basolaterally located "NHE1-related"
      transport activity. Regulatory control of intracellular Na/H exchange activities
      (apically versus basolaterally located) and intercellular Na/H exchange
      activities (NHE1-related) differs. This may relate to cell-specific properties as
      well as to exchanger-specific properties.

PMID- 8272383
TI  - Unitary delayed rectifier channels of rat hippocampal neurons: properties of
      block by external tetraethylammonium ions.
AB  - Patch-clamp recording was used to characterise a delayed rectifier potassium
      channel and the effects of external tetraethylammonium (TEA) in neurons isolated
      from the CA1 region of cultured neonatal rat hippocampus. A preliminary kinetic
      analysis is presented. Very low concentrations of TEA included in the patch
      pipette solution had two effects on unitary currents: first unitary currents were
      reduced in amplitude, with an associated increase in open channel noise, and
      second channel mean open time was reduced. The reduction in unitary amplitude was
      consistent with a single TEA molecule blocking the channel with a voltage
      independent Kd of 53.4 microM. The blocking and unblocking rate constants,
      estimated using two independent methods, were approximately 350 mM-1 ms-1 and 20
      ms-1, both rate constants being independent of voltage. Channels blocked in this
      way appeared able to close normally without first having to become unblocked. The
      reduction in mean channel open time was probably due to a second, kinetically
      slower blocking reaction with a much lower Kd, probably between 300 and 800
      microM. The voltage-independent blocking rate constant of the slower block was at
      least 25 times slower than that of the faster block.

PMID- 8272384
TI  - Influence of dietary NaCl intake on renin gene expression in the kidneys and
      adrenal glands of rats.
AB  - The aim of this study was to examine the influence of dietary NaCl intake on
      renin gene expression in the kidneys and adrenal glands of adult rats. Rats were
      kept on low (0.02%, w/w), normal (0.6%) or high (4%) NaCl diets and plasma renin
      activity (PRA) and the relative abundance of renin messenger ribonucleic acid
      (mRNA) in renal and adrenal tissue were followed for 20 days. In animals on a
      normal-salt diet PRA and renal renin mRNA levels did not change with time. PRA
      values in animals on the low-salt diet increased transiently (about threefold)
      and then declined again during the third week of treatment. Renal renin mRNA
      levels in these animals paralleled the changes of PRA. Conversely, in the animals
      kept on a high-salt diet PRA values decreased transiently and renal renin mRNA
      decreased continuously to about 50% of control values. Arterial blood pressure
      measured in conscious animals was not significantly influenced by the different
      salt diets. To establish whether the changes in renin mRNA levels are mediated by
      renal nerve input, animals on the different diets were also studied after
      unilateral renal denervation. Renal nerve section led to a 50% decrease of renin
      mRNA levels in the denervated kidneys in animals kept on the normal-salt diet. In
      the animals on the low-salt diet renin mRNA rose to similar levels in the
      denervated to those in the innervated kidney, while in animals receiving a high
      salt diet renin mRNA was further decreased in the denervated kidneys.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8272385
TI  - Cultured retinal pigment epithelial cells from RCS rats express an increased
      calcium conductance compared with cells from non-dystrophic rats.
AB  - The Royal College of Surgeon (RCS) rats suffer from a retinal dystrophy that is
      caused by a malfunction of the retinal pigment epithelium (RPE). We compared the
      membrane currents of cultured RPE cells from non-dystrophic and RCS rats by using
      the whole-cell configuration of the patch-clamp technique. Cultured RPE cells
      from RCS rats showed voltage-dependent, barium- and 4-aminopyridine-sensitive
      outward currents, which had characteristics of the delayed-rectifier and voltage
      dependent, barium- and 4-aminopyridine-sensitive inward currents, which had
      characteristics of the inward rectifier. Differences between RPE cells from RCS
      rats and normal rats were as follows. (a) Cultured RCS rat RPE cells showed a
      resting potential and an activation threshold for the voltage-dependent outward
      current significantly more positive than that found in cells from non-dystrophic
      rats. (b) In the presence of 10 mM barium, the voltage-dependent outward current
      was reduced in both types of cells; in cells from RCS rats, an additional voltage
      dependent inward current was observed. (c) This additional inward current had
      characteristics of L-type calcium channels and was reduced by verapamil (30
      microM) and diltiazem (30 microM). In summary, we conclude that the membrane
      conductances of RPE cells from normal and RCS rats are dominated by potassium
      conductances. In contrast to cells from non-dystrophic rats, cells of RCS rats
      expressed an increased membrane conductance for calcium.

PMID- 8272386
TI  - Ca2+ release in cultured rat epididymal cells during hypoosmotic swelling.
AB  - Microfluorimetric studies were carried out to investigate the effects of
      hypoosmotic swelling on intracellular Ca2+ concentration ([Ca2+]i) in single rat
      epididymal cells. In Ca(2+)-free solution containing 50 mumols/l
      ethylenebis(oxonitrilo)tetraacetate (EGTA) hypoosmotic swelling (-160 mosmol/l)
      induced a transient rise in [Ca2+]i which was either monophasic, biphasic or
      oscillatory. The [Ca2+]i responses to repeated hypoosmotic stimulations followed
      a decremental pattern. However, if 2.5 mmol/l Ca2+ was admitted during the
      recovery period between successive stimulations, the second and the third [Ca2+]i
      responses were slightly greater than the first. Increasing the change in
      osmolarity from -14 +/- 1.0 to -154 +/- 1.5 mosmol/l increased the rise in
      [Ca2+]i but reduced the [Ca2+]i response to subsequent ionomycin stimulation (4
      mumols/l). The swelling- and the ionomycin-induced rises in [Ca2+]i followed a
      reciprocal pattern. It was suggested that intracellular Ca2+ release in response
      to cell swelling in the epididymal epithelium might play a role in cell volume
      regulation and the control of epididymal fluid osmolarity.

PMID- 8272387
TI  - Contractile properties of skinned preparations from ischaemic canine myocardium
      and coronary arteries.
AB  - The influence of prolonged ischaemia on the regulation of contraction in the
      myocardium and in the smooth muscle of coronary arteries was investigated.
      Chemically skinned preparations were used which enabled the contraction to be
      studied with the environment of the contractile filaments controlled. Myocardial
      ischaemia was produced in anesthetized adult beagle dogs by occlusion of the left
      anterior descending artery for 3 h and followed by 30 min reperfusion. Myocardial
      tissue and segments from coronary arteries were obtained from the ischaemic
      infarcted wall region ("in vivo ischaemic") and compared with control
      preparations from perfused coronary arteries and from the free wall of the left
      ventricle. Coronary and myocardial preparations were also obtained from the heart
      after a 3 h period in vitro under anoxic conditions at 37 degrees C ("in vitro
      ischaemic") simulating a state of extreme ischaemia. Control myocardial fibres
      were fully relaxed at pCa (-log-[Ca2+]) 9 and developed 24 +/- 5% (n = 7) of
      maximum force at intermediate calcium concentration (pCa 5.5). In contrast, the
      in vivo and in vitro ischaemic preparations produced force at pCa 9 (28 +/- 13
      and 39 +/- 8%, respectively, n = 5 and 7) and showed an increased force
      development at pCa 5.5 (53 +/- 11 and 75 +/- 5%). The in vivo and in vitro
      ischaemic coronary arteries relaxed more slowly following calcium removal than
      control vessels. The in vitro ischaemic vascular preparations developed active
      force at pCa 9 and showed increased levels of myosin light chain phosphorylation
      and reduced phosphatase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272388
TI  - Myosin light chain phosphorylation during staircase in fatigued skeletal muscle.
AB  - It has been reported that the peak of the staircase or the enhanced tension
      response during low frequency stimulation is delayed in fatigued fast muscle. Our
      purpose was to determine if the rate and extent of regulatory myosin light chain
      (P-LC) phosphorylation, a molecular mechanism associated with the positive
      staircase, are also altered by fatigue. The staircase contractile response,
      muscle metabolites and phosphate incorporation by the P-LC were assessed at 0, 5,
      10 or 20 s of 10-Hz stimulation, in either non-fatigued (control) or fatigued (10
      Hz for 5 min, followed by 20 min of recovery) rat gastrocnemius muscle in situ.
      The concentration of adenosine triphosphate (ATP) in fatigued muscles, 21 +/- 0.9
      mmol.kg-1 (dry weight) was significantly lower (P < 0.05) than in the control
      muscles, 26.1 +/- 1.5 mmol.kg-1. In both groups, ATP content was significantly
      lower after 20 s of 10 Hz stimulation. The P-LC phosphate content (in mol
      phosphate.mol-1 P-LC) was 0.10, 0.38, 0.60 and 0.72 after 0, 5, 10 or 20 s of 10
      Hz stimulation in control muscles, but only 0.03, 0.08, 0.11 and 0.19 at these
      times in fatigued muscles. Although the absolute magnitude of tension
      potentiation was attenuated in proportion to the depressed twitch amplitude,
      these surprisingly low levels of phosphorylation were associated with 0, 48, 79
      and 86% potentiation of the developed tension at these times in contrast with 0,
      71, 87 and 49% potentiation in control muscles. These data demonstrate that while
      the rate and extent of phosphate incorporation is depressed in fatigued muscle,
      tension potentiation is still evident.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272389
TI  - Activation of ion transport by combined effects of ionomycin, forskolin and
      phorbol ester on cultured HT-29cl.19A human colonocytes.
AB  - The differentiated clone 19A of the HT-29 human colon carcinoma cell line was
      used as a model to study the intracellular electrophysiological effects of
      interaction of the cAMP, the protein kinase C (PKC) and the Ca2+ pathways. (a) A
      synergistic effect between ionomycin and forskolin was observed. From
      intracellular responses it was concluded that the synergistic effect is caused by
      activation of an apical Cl- conductance by protein kinase A and a basolateral K+
      conductance by Ca2+. (b) A transient synergistic effect of ionomycin and the
      phorbol ester phorbol dibutyrate (PDB) was found. The decrease of the response
      appeared to be due to PKC-dependent inactivation of the basolateral K+
      conductance. The synergism is caused by PKC-dependent increase of the apical Cl-
      conductance and Ca(2+)-dependent increase of the basolateral K+ conductance. (c)
      The effects of carbachol and PDB were not fully additive presumably because of
      their convergence on PKC activation. (d) Forskolin and PDB, when added in this
      order, had a less than additive effect. Results of cell-attached patch-clamp
      studies, presented in the accompanying paper, showed a synergistic effect of
      forskolin and PDB on non-rectifying small-conductance Cl- channels. Assuming that
      these channels are involved in the transepithelial responses it is suggested that
      forskolin and PDB induce a modulatory, synergistic increase of the apical Cl-
      conductance when both pathways are activated simultaneously. (e) The HT-29cl.19A
      cells differ from T84 cells in that the latter did n ot respond with an increase
      of the short-circuit current to addition of phorbol ester. this may be due to a
      very low expression of PKA alpha.

PMID- 8272390
TI  - [Priority setting--a matter of concern for everybody].

PMID- 8272391
TI  - [The Patient Earth--physicians' responsibility?].
AB  - During this century the discipline of community medicine has been confronted with
      three major threats to public health: former infectious diseases, contemporary
      life-style diseases, and impending environmental diseases. A new approach to
      community medicine, with an ecological profile and a focus on the interplay
      between politics, economics, biology, the environment and public health, may
      become the medical profession's most important instrument for contending with
      environmental diseases. By shedding light on destroyed ecosystems and health
      injuries, community medicine may contribute to the evolution of informed and
      effective opinion, and by keeping administrators and politicians informed of
      research findings and their consequences, promote ecologically compatible
      decision-making.

PMID- 8272392
TI  - [Rehabilitation of back problems in Finland--effect of illness certificate and
      early disability retirement].
AB  - The effectiveness of rehabilitation has been studied in large series of Finnish
      patients with chronic low back pain. If the criterion of efficacy is reduction in
      the extent of sick leave and the incidence of disability pensions, the results
      are modest. Simple out-patient treatment yielded results comparable to those of
      costly treatment programmes at rehabilitation centres. Although intensive
      physical training increased mobility, muscular strength and endurance test
      values, it had no beneficial effect on figures for sick leave and disability
      retirement. To achieve better results in rehabilitation, the psychosocial factors
      involved in low back pain need to be taken into account as important components
      of the illness.

PMID- 8272393
TI  - [Why intensive rehabilitation of patients with chronic back problems?].
AB  - When patients with chronic back trouble are improved after intensive
      rehabilitation, in all likelihood it is due more to changes in pain behaviour
      than to physiological effects of treatment. The Copenhagen Spine Center at the
      Danish national hospital, Rigshospitalet has launched an eight hours a day, three
      week programme of cardiovascular fitness, progressive weight training,
      stretching, ergonomics, psychology and an extended back school, with a view to
      modifying the self-image and pain behaviour of long term sick-certificated
      patients with back problems, in order to enable them to return to work.

PMID- 8272395
TI  - [Sweden introduces a system of family physicians. Concern among district
      physicians].

PMID- 8272394
TI  - [Back health--team work between health care and insurance fund].

PMID- 8272396
TI  - [Effects of psychotherapy in schizophrenia. What conclusions can be drawn from
      the Abo Project?].

PMID- 8272397
TI  - [NordRAI analyses geriatric care in Scandinavia].
AB  - A Nordic project, NordRAI, has been launched to provide a common basis for the
      evaluation of institutionalised geriatric care. It is hoped that the project will
      shed light upon differences in practice, quality, and the use of resources, and
      that the resulting findings will enable more rapid improvements to be made in the
      care of the elderly.

PMID- 8272398
TI  - [Handbook for rotation candidates--Norwegian experiences].
AB  - Clinical handbooks and procedure descriptions have been suggested as a way to
      improve the practical part of the medical education in Norway, but experience
      with books of this type is scarce, and the applicability of the model has been
      questioned. This paper reports a questionnaire survey among Norwegian medical
      students who have had hands-on experience with such a book throughout their
      student practice. The book apparently has been used, and no serious criticism has
      been put forward. It is an obvious sine qua non that such a book is used with
      proper care, and that the cooperation with senior doctors on duty is maintained.

PMID- 8272399
TI  - Biotechnology and bone graft substitutes.
AB  - Trauma, disease, developmental deformities, and tumor resection frequently cause
      bone defects that seriously challenge the skills of orthopedic and maxillofacial
      surgeons. Currently, repairing osseous deficiencies involves various medical
      surgical techniques, including autogenous grafts, allografts, internal and
      external fixation devices, electrical stimulation, and alloplastic implants. The
      existing technology, though effective in many cases, still is beset with numerous
      difficulties and disadvantages. A critical need for improved treatment methods
      exists today. Biotechnology now provides access to new bone repair concepts via
      administration of protein growth and morphogenic factors. Implantable device and
      drug delivery system technologies also have advanced. The converging
      biopharmaceutical, device, and delivery technologies represent an opportunity to
      improve the quality of health care for individuals with orthopedic and
      maxillofacial deficiencies. This report reviews current concepts in fracture
      healing and bone repair and examines existing treatment modalities. It also
      addresses novel protein drugs that stimulate osseous regeneration and delivery
      systems for these drugs.

PMID- 8272400
TI  - Enhancement of tissue delivery and receptor occupancy of methylprednisolone in
      rats by a liposomal formulation.
AB  - A liposomal formulation of methylprednisolone (L-MPL) was developed to improve
      localization of this immunosuppressant in lymphatic tissues. Liposomes containing
      MPL were formulated from a mixture of phosphatydylcholine and
      phosphatydylglycerol (molar ratio, 9:1) and sized by extrusion through a 0.1
      micron membrane. Male Sprague-Dawley rats received a bolus dose of 2 mg/kg of L
      MPL or free MPL in solution (control). Samples of blood, spleen, liver, thymus,
      and bone marrow were collected at intervals over a 66-hr period. Concentrations
      of MPL in plasma and organs and free cytosolic glucocorticoid receptors (GCR) in
      spleen and liver were determined. The plasma MPL profiles for free and L-MPL were
      bi- and triexponential. Although the alpha phase kinetics of both dosage forms
      were similar, L-MPL showed a substantially slower elimination phase than did free
      drug. Incorporation of MPL into liposomes caused the following increases:
      terminal half-life, from 0.48 (MPL) to 30.13 hr (L-MPL); MRT, from 0.42 to 11.95
      hr, Vss, from 2.10 to 21.87 L/kg; and AUC, from 339 to 1093 ng x hr/mL. Uptake of
      liposomes enhanced significantly the delivery of drug to lymphatic tissues and
      liver; AUC tissue:plasma ratios for spleen increased 77-fold; for liver, 9-fold;
      and for thymus, 27-fold. The duration of GCR occupancy was extended 10-fold in
      spleen and 13-fold in liver by the liposomal formulation. Lymphatic tissue
      selectivity and extended receptor binding of liposome-delivered MPL offer promise
      for enhanced immunosuppression.

PMID- 8272402
TI  - Precision, accuracy, and data acceptance criteria in biopharmaceutical analysis.
AB  - Accuracy and precision are the most important criteria in the assessment of an
      analytical method, and monitoring quality control during sample analysis is
      essential to ensure the validity of reported results. Various approaches to
      testing accuracy, precision, and quality control were applied to 10 analytes from
      seven chromatographic bioanalytical methods. These methods include fixed interval
      bias and significance testing for accuracy; fixed interval percentage relative
      standard deviation (%RSD) and analysis of variance (ANOVA) approaches for
      precision; +/- 20% fixed range, 99% confidence interval, multiple rules, and
      range chart for individuals approaches for quality control acceptance criteria.
      Quality control approaches were also applied to the entire run and to a bracketed
      approach whereby results are considered valid only if bracketed by acceptable
      quality control. Accuracy and precision were assessed for six runs of each
      analyte at three concentrations established to represent the calibration range of
      the analytical method. Quality control acceptance criteria were evaluated using
      all data sets from each of the analytical methods collected during the course of
      running various numbers of real samples. The data suggest that the fixed interval
      bias criteria for accuracy was a more liberal method of accuracy assessment
      because three of the seven methods would have been rejected according to the
      significance testing criteria whereas all were acceptable by the fixed internal
      bias criteria. Precision can be effectively assessed for between- and within-run
      data by criteria set on unconfounded %RSD values or by separation of the sources
      of variation using an ANOVA approach applied to confounded data.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8272401
TI  - Microdialysis calibration using retrodialysis and zero-net flux: application to a
      study of the distribution of zidovudine to rabbit cerebrospinal fluid and
      thalamus.
AB  - A retrodialysis (RD) method for the real-time calibration of on-line
      microdialysis (MD) procedures was investigated in vitro and in vivo. Calibration
      by retrodialysis was simultaneously validated through the use of a zero-net flux
      (ZNF) method, which assumes directional independence of diffusion of the solute.
      In RD, a calibrator with dialysance (PeA; effective permeability-surface area
      product) similar to that of the compound of interest is introduced into the
      perfusate. If the calibrator is suitable, its loss from the perfusate during RD
      is identical to the recovery of the solute of interest determined simultaneously
      by normal MD. Two antiviral nucleosides (AZT and AZdU) which differ structurally
      by only a methylene group were utilized as solute and calibrator, respectively.
      Both nucleosides exhibited similar recovery and loss at flow rates of 0.5 to 5
      microL/min in vitro, indicating a similar PeA product in this flow domain.
      Furthermore, both compounds showed similar loss into the lateral ventricle or
      thalamus of rabbits (n = 4) during RD at a flow rate of 1 microL/min for 6 hr.
      The relative loss decreased rapidly within the first hour, reaching a relatively
      stable value after 2 hr. The significant reduction in the loss of AZdU and AZT in
      vivo compared with that in vitro likely results from a lower diffusion
      coefficient in tissue. The distribution of AZT between plasma and cerebrospinal
      fluid (CSF) in the ventricle and extracellular fluid (ECF) in thalamus was
      determined at steady state using calibration by RD and ZNF
      simultaneously.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272403
TI  - Inhibition of the Friend retrovirus by antisense oligonucleotides encapsulated in
      liposomes: mechanism of action.
AB  - Proliferation of the Friend retrovirus was specifically inhibited by the env mRNA
      complementary oligonucleotide encapsulated in pH-sensitive liposomes. This
      observation was made using the focus immunoassay (FIA) and the reverse
      transcriptase test. The key finding of the present study was the dramatic impact
      on liposome penetration. For chronic or de novo infection, the point at which the
      penetration of liposomes began corresponded to the time needed for the virus to
      leave the cell. In the absence of the virus, liposomes remained adsorbed onto the
      cell surface without any internalization. Regardless of the mechanism involved,
      the fact that a retroviral infection stimulates the cellular uptake of
      oligonucleotide liposomes widens the spectrum of strategies for specific
      antiviral action.

PMID- 8272404
TI  - Modulation of human ovarian tumor cell sensitivity to N-(phosphonacetyl)-L
      aspartate (PALA) by liposome drug carriers.
AB  - Carrier-based formulations of cytotoxic agents may be highly efficacious for
      intracavitary therapy of malignancies which reside in or metastasize to the
      peritoneal cavity. N-(Phosphonacetyl)-L-aspartic acid (PALA) is a transition
      state inhibitor of aspartate transcarbamylase which has shown enhanced activity
      against several cell lines upon encapsulation in liposomes. We have examined the
      growth inhibitory effects of PALA-containing liposome formulations against four
      human ovarian cancer cell lines (Ovcar-3, Hey-1b, A90, and A121a) that have
      significantly different growth characteristics. With the optimal liposome
      formulation defined in the present studies, the potency of encapsulated PALA was
      22- to 570-fold greater than that of free PALA, depending on the cell line.
      Control liposomes containing buffer, rather than PALA, did not inhibit cell
      growth. Fluorescence studies of liposome-cell interaction suggest that high
      liposome negative surface charge density and high phase transition temperature
      increase both cellular association and retention of liposome contents. Briefer
      exposure of tumor cells to treatment accentuates the advantage of liposome
      formulations; on Hey-1b cells, the cytostatic effect of 1-hr exposure to PALA
      liposomes is 900-fold greater than is the equivalent exposure to free PALA. The
      considerable increase in in vitro potency of PALA-liposome formulations, coupled
      with potential pharmacokinetic advantages in vivo (i.e., intraperitoneal
      retention of liposome-associated drug versus rapid clearance of free PALA),
      suggests the possibility of enhanced antitumor activity of liposome-encapsulated
      PALA for both single-agent and combination chemotherapy.

PMID- 8272405
TI  - Pharmacokinetics, mass balance, and induction potential of a novel GABA uptake
      inhibitor, CI-966 HCl, in laboratory animals.
AB  - CI-966 exhibits anticonvulsant properties in various animal models. The drug acts
      by inhibiting synaptic uptake of gamma-aminobutyric acid (GABA). Oral absorption
      of CI-966 in dogs given 1.39 mg/kg is rapid with a tmax of 0.7 hr. In rats given
      5 mg/kg oral, a mean tmax of 4.0 hr was observed. Following iv administration of
      the same respective doses, elimination t1/2 in dogs and rats averaged 1.2 and 4.5
      hr. Absolute oral bioavailability of CI-966 was 100% in both species. Following
      oral dosing of [14C]CI-966 HCl to dogs, fecal, and urinary excretion accounted
      for 89% and 2.3% of the 14C dose, respectively. In bile-duct cannulated rats,
      biliary excretion is the major elimination pathway of radioactivity (75%).
      Urinary and fecal excretion accounted for 4.1 and 12%, respectively. CI-966 does
      not induce or inhibit mouse hepatic mixed function oxidases, as determined by
      hexobarbital sleeping time.

PMID- 8272406
TI  - Plasma pharmacokinetics of lactone and carboxylate forms of 20(S)-camptothecin in
      anesthetized rats.
AB  - 20(S)-Camptothecin exists in equilibrium between its lactone (CPT) and its
      carboxylate forms (Na-CPT) under stimulated physiological conditions, with the
      equilibrium favoring the carboxylate form. The rates of lactone hydrolysis were
      studied in plasma, serum albumin, and blood and were found to be faster than in
      aqueous buffers at equivalent pH values. From mechanistic information and in vivo
      activity data, the lactone appears to be the active form of the drug. It has been
      argued, therefore, that if an equilibrium existed between the lactone and the
      carboxylate, Na-CPT could be used to deliver the lactone effectively. In the
      present study, plasma pharmacokinetics were performed in sodium pentobarbital
      anesthetized rats treated with both CPT (lactone) and the sodium salt of
      camptothecin (carboxylate, Na-CPT) and the lactone and carboxylate, as well as
      the total drug, concentration versus time profiles were assessed. It was found
      that plasma concentrations and AUC values for the lactone were significantly
      higher after dosing with CPT than after dosing with Na-CPT. After i.v.
      administration, the ratio of plasma lactone to carboxylate was skewed by the
      apparent rapid and extensive uptake of the lactone into tissues and the rapid
      clearance of both species. From our results, it appears that the lower in vivo
      activity of Na-CPT compared to that from CPT administration might be attributed
      to the altered conversion of carboxylate into lactone in vivo compared to that
      predicted from in vitro data.

PMID- 8272407
TI  - The effect of aluminum hydroxide dissolution on the bleeding of aluminum lake
      dyes.
AB  - The effect of pH on the bleeding of FD&C yellow No. 5 aluminum lake and FD&C red
      No. 40 aluminum lake was investigated. The pH-bleeding profiles corresponded to
      the pH-solubility profile of aluminum hydroxide. The similarity of the bleeding
      profiles of both lake dyes and the pH-solubility profile of aluminum hydroxide
      indicates that pH related bleeding, other than that occurring by competition with
      anions, is a result of dissolution of the aluminum hydroxide substrate. This
      dissolution is related to the properties of the substrate rather than to the
      structure of adsorbed dye.

PMID- 8272408
TI  - The interconversion kinetics, equilibrium, and solubilities of the lactone and
      hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981.
AB  - The pH dependence of the interconversion kinetics, equilibrium, and solubilities
      of the lactone and hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981
      ([R-(R*,R*)]-2-(4-fluorophenyl)- beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl
      4-[(phenylamino)carbonyl ]- 1H-pyrrole-1-hepatonic acid), are important
      considerations when choosing and developing one of the forms of these compounds.
      Over a pH range of 2.1 to 6.0 and at 30 degrees C, the apparent solubility of the
      sodium salt of CI-981 (i.e., the hydroxyacid form) increases about 60-fold, from
      20.4 micrograms/mL to 1.23 mg/mL, and the profile yields a pKa for the terminal
      carboxyl group of 4.46. In contrast, over a pH range of 2.3 to 7.7 and also at 30
      degrees C, the apparent solubility of the lactone form of CI-981 varies little,
      and the mean solubility is 1.34 (+/- 0.53) micrograms/mL. The kinetics of
      interconversion and the equilibrium between the hydroxyacid and the lactone forms
      have been studied as a function of pH, buffer concentration, and temperature at a
      fixed ionic strength (0.5 M) using a stability-indicating HPLC assay. The acid
      catalyzed reaction is reversible, whereas the base-catalyzed reaction can be
      treated as an irreversible reaction. More specifically, at pH < 6, an equilibrium
      favoring the hydroxyacid form is established, whereas at pH > 6, the equilibrium
      reaction is no longer detectable and greatly favors the hydroxyacid
      form.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272409
TI  - Synthesis and stability of isotopically labeled p-chloro-m-xylenol (PCMX).
AB  - The synthesis, reaction kinetics, and pH stability of isotopically labeled p
      chloro-m-xylenol (PCMX) were evaluated. While base catalysis was more rapid than
      acid catalysis, the latter allowed the use of a cosolvent for deuterium and
      tritium labeling using as little as 250 microL labeled water. Both acid and base
      catalysis were markedly more rapid than that reported previously for the
      deuteration of PCMX and related phenols. Isotopic labeling occurred only at the 2
      and 6 ring positions, ortho to the phenolic group of PCMX. No deuterium loss was
      observed after storage for 21 days at 37 degrees C over a pH range of 2-14.
      Isotopic loss was observed only below pH 2. The prepared 3H-labeled PCMX had a
      specific activity of 1.18 mCi/mmol, a radiochemical purity of 99.0%, and a
      chemical purity exceeding 99.0%, with a high stability during prolonged cold
      storage.

PMID- 8272410
TI  - Validation of a peptide map for recombinant porcine growth hormone and
      application to stability assessment.
AB  - A reverse-phase HPLC method for the analysis of tryptic digests of recombinant
      porcine growth hormone (pGH) has been developed and validated. Digestion was
      performed at 4 degrees C for a 20-hr period with TPCK-treated trypsin at a 1:20
      (w/w) trypsin:pGH ratio. Gradient elution HPLC, using an Aquapore RP300 C8
      column, was incorporated for separation of the digestion products and peak
      identification was carried out by mass spectrometry (MS). The digestion procedure
      and subsequent chromatography were linear in the initial concentration range of
      4.55-45.46 microM (100 to 1000 micrograms/mL) pGH. The variability in the
      fragment retention times was low and the normalized peak area variability was
      less than 5% for all but three of the fragments. The utility of the trypsin
      digestion and chromatography procedures has been demonstrated by assessing
      chemical changes in pGH induced by incubation at elevated pH. Upon incubation of
      pGH in 0.2 M Tris buffer at pH 9 (ionic strength adjusted to 0.5 with NaCl) and
      37 degrees C over a period of 400 hr, significant degradation in the regions
      corresponding to the digestion fragments T23-T25 (residues 181-182 linked by a
      disulfide bond to residues 184-191), T9 (residues 96-108), and T5-T18 (residues
      43-64 linked by a disulfide bond to residues 158-166) was observed. The
      disappearance of the peaks corresponding to fragments T23-T25 and T9 both
      displayed apparent first-order degradation kinetics over the time period
      investigated with half-lives of 131 and 154 hr, respectively.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8272411
TI  - The effect of salts on the stability of beta-galactosidase in aqueous solution,
      as related to the water mobility.
AB  - The effect of salts (KI, KBr, NaCl, KCl, KF, phosphate, and Na2SO4) on the
      stability of beta-galactosidase in aqueous solution was studied from the aspect
      of changes in water mobility. At salt concentrations up to 200 mM, the
      inactivation rate of beta-galactosidase in all the salt solutions studied
      increased with increasing salt concentration. At higher concentrations, those
      salts which had little effect on the spin-lattice relaxation time, T1, of water
      (KI, KBr, and KCl) continued to increase the inactivation rate of beta
      galactosidase with increasing concentration, while those salts which decreased
      the T1 of water (KF, phosphate, and Na2SO4) decreased the inactivation rate. It
      appeared that the decrease in water mobility caused by KF, phosphate, and Na2SO4
      resulted in stabilization of beta-galactosidase. The results indicate that water
      mobility is an important factor in the denaturation rate of proteins.

PMID- 8272412
TI  - Development of new lipophilic derivatives of tetragastrin: physicochemical
      characteristics and intestinal absorption of acyl-tetragastrin derivatives in
      rats.
AB  - In order to improve the intestinal absorption of tetragastrin (TG), we
      synthesized lipophilic derivatives of TG by acylation of its N-terminal amino
      group with acetic acid, caproic acid, and lauric acid. The purified TG
      derivatives, acetyl-tetragastrin (Ac-TG), caproyl-tetragastrin (Cap-TG), and
      lauroyl-tetragastrin (Lau-TG), were confirmed to be more lipophilic than the
      parent TG by high-performance liquid chromatography (HPLC). The pharmacological
      activities and the intestinal absorption of TG and its derivatives were examined
      by measuring gastric acid secretion. Stimulation of gastric acid secretion by
      these derivatives after intravenous administration was stronger than with native
      TG. When the acetyl- and caproyl-derivatives were administered into the large
      intestinal loops, a marked increase in gastric acid secretion was observed in
      comparison with TG, while no significant effect occurred following administration
      of the TG derivatives into the small intestines. These results indicated that
      chemical modification of TG with fatty acids improves the absorption of TG from
      the large intestines.

PMID- 8272413
TI  - Histocultures of patient head and neck tumors for pharmacodynamics studies.
AB  - This investigation was to establish a clinically relevant experimental model to
      evaluate the pharmacodynamics of drugs used for head and neck cancers. A total of
      83 surgical samples of primary and lymph nodal metastatic tumors was obtained
      from 66 patients. Fragments of these tumors were cultured on a collagen gel
      matrix. The tumor cell labeling index (LI) was determined by [3H]thymidine
      incorporation and autoradiography. Seventeen tumors (20%) were contaminated.
      About 80% of the remaining 65 tumors were successfully cultured for at least 2
      weeks. The cultured tumor fragments retained the morphology and architecture of
      the freshly removed specimens; both tumor and stromal cells were present. The
      tumor cell LI after 2-3 weeks in culture, determined from the most proliferative
      area of the tissue, averaged 77 +/- 12% for primary tumors and 78 +/- 12% for
      nodal metastases. The activity of three clinically active agents, 5-fluorouracil
      (FU), cisplatin (DDP), and mitomycin C (MMC), was evaluated in 47 tumors. All
      three drugs inhibited the tumor LI. The concentrations needed to produce a 50%
      inhibition of the tumor LI (IC50) were within the clinically achievable
      concentration range. The intertumor variation in the IC50 for FU (60-fold) was
      considerably greater than that for DDP and MMC (7- to 8-fold). The nodal
      metastatic tumors appeared to be less sensitive to FU than the primary tumors,
      while there were no apparent differences for DDP or MMC.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8272414
TI  - Validation of reflectance infrared spectroscopy as a quantitative method to
      measure percutaneous absorption in vivo.
AB  - Attenuated total-reflectance infrared (ATR-IR) spectroscopy has been used to
      follow the penetration of a model compound (4-cyanophenol; CP) across human
      stratum corneum (SC) in vivo, in man. CP was administered for periods of 1, 2, or
      3 hr, either (a) as a 10% (w/v) solution in propylene glycol or (b) in an
      identical vehicle which also contained 5% (v/v) oleic (cis-9-octadecenoic) acid.
      At the end of the treatment periods, SC at the application site was progressively
      removed by adhesive tape-stripping. Prior to the removal of the first tape-strip,
      and after each subsequent tape-strip, an ATR-IR spectrum of the treated site was
      recorded. The presence of CP, as a function of position in the SC, was monitored
      spectroscopically via the intense C = N stretching absorbance at 2230 cm-1. The
      absolute amount of CP, as a function of SC depth, was determined by "spiking" the
      applied solutions with 14C-labeled compound and subsequent liquid scintillation
      counting of the removed tape-strips. The presence of oleic acid in the applied
      formulation significantly increased the rate and extent of CP delivery as
      evaluated by either spectroscopy or radiochemical analysis. Furthermore, the ATR
      IR and direct 14C analysis of CP as a function of SC position were highly
      correlated. These data strongly support, therefore, the validation of ATR-IR as a
      quantitative tool to assess percutaneous penetration in vivo.

PMID- 8272415
TI  - Physicochemical characterization of high- and low-melting phenylephrine
      oxazolidines.
AB  - Phenylephrine oxazolidine is a new prodrug of phenylephrine developed for
      improving ocular absorption and reducing systemic side effects. In the present
      study, high- and low-melting phenylephrine oxazolidines (HMP and LMP) were
      characterized in terms of their stereochemistry and crystal properties. It was
      found that the molecular configuration of the prodrug in the crystals of either
      HMP or LMP is identical (5R/2R). The two crystals were shown to have the same IR
      spectra and X-ray diffraction patterns but different crystal habits, thermal
      properties, solubilities and intrinsic dissolution rates. Single crystal X-ray
      structure analysis indicates that crystals of both HMP and LMP are orthorhombic
      and belong to the P2(1)2(1)2(1) space group with four molecules in a unit cell (a
      = 20.697 A, b = 7.065 A, and c = 9.304 A). The molecules in the crystal are held
      together by an intermolecular hydrogen bonding interaction between N(3) and
      O(13). The different physical properties observed for LMP result from crystal
      imperfections caused by the presence of trace amounts (often at levels < 0.5%) of
      an unidentified, structurally related synthetic impurity which can be dispersed
      in the prodrug. It was observed that both HMP and LMP can sustain thermal and
      mechanical treatment in the solid state. However, LMP was partially converted to
      HMP when suspended in certain solvents.

PMID- 8272416
TI  - Enhanced bioavailability of cefoxitin using palmitoylcarnitine. II. Use of
      directly compressed tablet formulations in the rat and dog.
AB  - The performance of tablets containing the absorption enhancer palmitoylcarnitine
      chloride (PCC) and the antibiotic cefoxitin (CEF) was determined by direct
      placement of tablets in the rat stomach, small intestine, and colon. While the
      bioavailability (F) of tablets containing 12 mg CEF without PCC ranged from 0.6
      to 3.9%, the addition of 24 mg PCC resulted in an enhanced CEF bioavailability in
      the rat colon (mean +/- SD: F = 57 +/- 19%) and rat jejunum (F = 71 +/- 16%) but
      not in the rat stomach. Following oral administration to dogs, tablets of 200 mg
      CEF without or with 600 mg PCC resulted in the same low bioavailabilities (7.0 +/
      10.3 and 7.0 +/- 3.6%, respectively). However, when these tablets were enteric
      coated, PCC improved CEF bioavailability from 2.44 +/- 1.84 to 29.0 +/- 13.4%.
      Therefore, the use of enteric-coated direct compressed tablets containing PCC and
      direct compression excipients improved the peroral bioavailability of a poorly
      absorbed compound.

PMID- 8272417
TI  - Flow-through system effects on in vitro analysis of transdermal systems.
AB  - The development of transdermal therapeutic systems (TTS) often involves in vitro
      evaluation of formulations and prototypes using flow-through diffusion cells. The
      apparent flux obtained from such methodologies does not accurately represent the
      actual (intrinsic) permeation of the compound through the skin. Flow-through
      system parameters, i.e., fraction collector tube volume, receiver cell volume,
      flow rate, and sampling interval, modify the flux yielding an apparent flux. Both
      finite-dose flux profiles and infinite-dose diffusional lag times are modified by
      these parameters. In this study, a transfer function is derived which describes
      the effect of these parameters. The intrinsic flux is calculated from apparent
      flux data using the transfer function and experimental flow-through system
      parameters. This allows the calculation of permeant flux profiles devoid of
      modification by the experimental methodology.

PMID- 8272418
TI  - Sustained local anesthetic release from bioerodible polymer matrices: a potential
      method for prolonged regional anesthesia.
AB  - Polyanhydride polymer matrices have been used successfully for sustained release
      of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl,
      and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3
      bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was
      measured in vitro following incubation of the drug-polymer matrices in phosphate
      buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions.
      Local anesthetics were released in a sustained manner yielding 90% cumulative
      drug release over periods ranging from 3 to 14 days. The kinetics of release
      varied with both the choice of local anesthetic and the method of drug
      incorporation into the matrix (hot melt versus compression molding). Polymer
      local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20%
      bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats.
      Reversible neural blockade was observed for 4 days in all animals. Polymer
      implants without local anesthetic showed no neural blockade. This technology
      could lead to methods of prolonged blockade of peripheral nerves or of
      sympathetic ganglia, which may be utilized for the management of postoperative
      pain, sympathetically maintained pain, or certain forms of chronic pain.

PMID- 8272419
TI  - Salt and mesophase formation in aqueous suspensions of lauric acid.
AB  - The solubility and solution behavior of lauric acid (LA) and its 1:1 acid soap
      (potassium hydrogen dilaurate) were investigated at 32 degrees C over a pH range
      of 2.5-8.5 and at varying KCl concentrations to examine the self-association of
      this long-chain carboxylic acid under these conditions. LA's solubility in water
      exhibited the classical pH dependence of a monocarboxylic acid with no evidence
      of self-association. In 0.1 M KCl between pH 6.3 and pH 7.3, filtered samples
      were turbid, suggesting the presence of high molecular weight aggregates
      (mesophase), which could be removed by ultrafiltration. The apparent LA
      solubility vs pH profile in ultrafiltered samples was consistent with a solid
      phase consisting of either the free acid (pH < 6.5) or potassium hydrogen
      dilaurate (pH > 6.5), again with no evidence of self-association to form low
      molecular weight species (dimers, etc.). Quasi-elastic light scattering (QLS)
      studies and mannitol trapping experiments indicated that vesicles were present in
      samples containing mesophase. The mesophase composition was characterized and a
      mass-action law for mesophase formation was developed to describe the apparent LA
      solubility versus pH in the mesophase region in terms of three parameters. The
      index of cooperativity, theta, indicated that the mesophase consists of
      approximately 25 molecules of LA with an acid:anion ratio, rho, of 1.7. The
      standard free energy of mesophase formation per mole of monomer was determined to
      be -6.3 kcal/mol. The aggregate size determined thermodynamically is several
      orders of magnitude less than that of the mesophase particle size determined by
      QLS measurements, suggesting that the LA monomer concentration in equilibrium
      with mesophase may be governed by a small unit domain of the vesicle. These
      observations may have a bearing on the thermodynamics of self-assembly of lipid
      bilayer membranes.

PMID- 8272420
TI  - Preparation and characterization of thermal- and pH-sensitive nanospheres.

PMID- 8272421
TI  - Intrapulmonary delivery of renin inhibitory peptides results in sustained release
      because of saturable transport.

PMID- 8272422
TI  - Organization of turnip yellow mosaic virus investigated by neutron small angle
      scattering at 80 K: an intermediate state preceding decapsidation of the virion?
AB  - The organization of turnip yellow mosaic virus has been investigated by neutron
      small angle scattering at 300 K and 80 K in buffers containing various amounts of
      D2O. We confirm that in native virions, no substantial part of the RNA is located
      at a radius larger than ca. 100-110 A, i.e., that there is very little
      interpretation of the RNA into the capsid. At 80 K, scattering curves do not
      depend much upon contrast, from 40% D2O to 100% D2O buffers, but are strongly
      affected by interparticle interference. We could, however, show that it is not
      the case for the subsidiary intensity maximum at q approximately 0.06 A-1. From
      the position of this maximum, we conclude that upon freezing, the radius of the
      capsid expands by c.a. 3.5% and the RNA penetrates deeply into the protein shell.
      Biological implications of this conformational change immediately preceding
      decapsidation are discussed.

PMID- 8272423
TI  - Conformational analysis of protein structures derived from NMR data.
AB  - A study is presented of the conformational characteristics of NMR-derived protein
      structures in the Protein Data Bank compared to X-ray structures. Both ensemble
      and energy-minimized average structures are analyzed. We have addressed the
      problem using the methods developed for crystal structures by examining the
      distribution of phi, psi, and chi angles as indicators of global conformational
      irregularity. All these features in NMR structures occur to varying degrees in
      multiple conformational states. Some measures of local geometry are very tightly
      constrained by the methods used to generate the structure, e.g., proline phi
      angles, alpha-helix phi,psi angles, omega angles, and C alpha chirality. The more
      lightly restrained torsion angles do show increased clustering as the number of
      overall experimental observations increases. phi, psi, and chi 1 angle
      conformational heterogeneity is strongly correlated with accessibility but shows
      additional differences which reflect the differing number of observations
      possible in NMR for the various side chains (e.g., many for Trp, few for Ser). In
      general, we find that the core is defined to a notional resolution of 2.0 to 2.3
      A. Of real interest is the behavior of surface residues and in particular the
      side chains where multiple rotameric states in different structures can vary from
      10% to 88%. Later generation structures show a much tighter definition which
      correlates with increasing use of J-coupling information, stereospecific
      assignments, and heteronuclear techniques. A suite of programs is being developed
      to address the special needs of NMR-derived structures which will take into
      account the existence of increased mobility in solution.

PMID- 8272424
TI  - Crystal structure of the complex of human alpha-thrombin and nonhydrolyzable
      bifunctional inhibitors, hirutonin-2 and hirutonin-6.
AB  - The crystal structure of the complexes of hirutonin-2 and hirutonin-6 with human
      alpha-thrombin have been solved and refined to R-factors of 0.169 (2.0 A
      resolution) and 0.162 (2.1 A), respectively. Hirutonins belong to a family of
      bifunctional inhibitors bearing a noncleavable moiety mimicking the scissile
      bond. Hirutonin-2 is an analog of (D)Phe-Pro-Arg-Gly-hirudin49-65; hirutonin-6
      has the same N-terminal tripeptide connected to a shortened fibrinogen exosite
      binding part by a short, nonpeptidyl linker. The hirutonin-6 molecule is well
      defined in the electron density with the exception of the C-terminal Leu-h61. The
      linker follows near the bottom of the canyon connecting the active site with the
      exosite, forms a short antiparallel beta-sheet-like arrangement with Leu40-Leu41
      and makes van der Waals contacts with Glu39-Leu40-Leu41 of thrombin. In the
      thrombin-hirutonin-2 complex, the N- and C-terminal parts of the inhibitor are
      well ordered (except the C-terminal Gln-h65) while the central portion of the
      linker is partially disordered. The glycine analog in the P1' position of
      hirutonin-2 assumes a conformation similar to that of the canonical form (Bode
      and Huber (1992) Eur. J. Biochem. 204:433-451) and supports the identification of
      the S1' site as restricted by His57, Trp60D, Lys60F, and the Cys42-Cys58
      disulfide bridge. The carbonyl oxygen of the P1 arginine residue is located in
      the oxyanion hole formed by the NH groups of Gly193 and Ser195, while the
      carbonyl carbon is positioned within a short distance, 2.8 A, from the O gamma of
      Ser195. This resembles the conformation of the substrate-like inhibitors bound to
      other serine proteases. The N-terminal (D)Phe-Pro-Arg fragment common to both
      inhibitors binds to thrombin in a fashion very similar to that of other
      inhibitors having this motif. The binding of the C-terminus of hirutonins to the
      fibrinogen-binding exosite is similar to that observed in hirudin and hirulog
      complexes.

PMID- 8272425
TI  - Orientational sampling and rigid-body minimization in molecular docking.
AB  - The biological activities of proteins depend on specific molecular recognition
      and binding. Computational methods for predicting binding modes can facilitate
      the discovery and design of ligands and yield information on the factors
      governing complementarity. The DOCK suite of programs has been applied to several
      systems; here, the degree of orientational sampling required to reproduce and
      identify known binding modes, with and without rigid-body energy minimization, is
      investigated for four complexes. There is a tradeoff between sampling and
      minimization. The known binding modes can be identified with intensive sampling
      alone (10,000 to 20,000 orientations generated per system) or with moderate
      sampling combined with minimization. Optimization improves energies
      significantly, particularly when steric clashes are present, and brings many
      orientations closer to the experimentally observed position. Whether or not
      minimization is performed, however, sampling must be sufficient to find at least
      one structure in the vicinity of the presumed true binding mode. Hybrid
      approaches combining docking and minimization are promising and will become more
      viable with the use of faster algorithms and the judicious selection of fewer
      orientations for minimization.

PMID- 8272426
TI  - Single-site modifications of half-ligated hemoglobin reveal autonomous dimer
      cooperativity within a quaternary T tetramer.
AB  - The patterns of energetic response elicited by single-site hemoglobin mutations
      and chemical modifications have been determined in order to probe the dimer-dimer
      interface of the half-ligated tetramer (species [21]) that was previously shown
      to behave as allosterically distinct from both the unligated and fully ligated
      molecules. In this study the free energies of quaternary assembly (dimers to
      tetramers) were determined for a series of 24 tetrameric species in which one
      dimeric half-molecule is ligated (cyanomet hemes) while the adjacent alpha beta
      dimer is unligated and contains a single amino acid modification. Assembly
      energies have also been determined for tetramers bearing the same amino acid
      modifications but where the hemesites were completely vacant and additionally
      where they were fully occupied. A total of 72 molecular species were thus
      characterized. It was found that mutationally induced perturbations to the free
      energy of quaternary assembly were identical for the half-ligated tetramers and
      the unligated tetramers over the entire spatial distribution of altered sites,
      but exhibited a radically different pattern from that of the fully ligated
      molecules. These results indicate that the dimer-dimer interface of the half
      ligated tetramer (species [21]) has the same quaternary structure as that of the
      unligated molecule, i.e., "quaternary T." This quaternary structure assignment of
      species [21] strongly supports the operation of a Symmetry Rule which translates
      changes in hemesite ligation into six T-->R quaternary switchpoints. Analysis of
      the observed Symmetry Rule behavior in relation to the measured distribution of
      cooperative free energies for the partially ligated species reveals significant
      cooperativity between alpha and beta subunits of the dimeric half-tetramer within
      quaternary T. The mutational results indicate that these interactions are not
      "paid for" by breaking or making noncovalent bonds at the dimer-dimer interface
      (alpha 1 beta 2). They arise from structural and energetic changes that are
      "internal" to the ligated dimer even though its association with the unligated
      dimer is required for the cooperativity to occur. Free energy of "tertiary
      constraint" is thus generated by the first binding step and is propagated to the
      second hemesite while the dimer-dimer interface alpha 1 beta 2 serves as a
      constraint. The "sequential" cooperativity that occurs within the half-molecule
      is thus preconditioned by the constraint of a quaternary T interface; release of
      this constraint by dissociation produces only noncooperative dimers.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8272427
TI  - A calculation strategy for the structure determination of symmetric dimers by 1H
      NMR.
AB  - The structure determination of symmetric dimers by NMR is impeded by the
      ambiguity of inter- and intramonomer NOE crosspeaks. In this paper, a calculation
      strategy is presented that allows the calculation of dimer structures without
      resolving the ambiguity by additional experiments (like asymmetric labeling). The
      strategy employs a molecular dynamics-based simulated annealing approach to
      minimize a target function. The experimental part of the target function contains
      distance restraints that correctly describe the ambiguity of the NOE peaks, and a
      novel term that restrains the symmetry of the dimer without requiring the
      knowledge of the symmetry axis. The use of the method is illustrated by three
      examples, using experimentally obtained data and model data derived from a known
      structure. For the purpose of testing the method, it is assumed that every NOE
      crosspeak is ambiguous in all three cases. It is shown that the method is useful
      both in situations where the structure of a homologous protein is known and in ab
      initio structure determination. The method can be extended to higher order
      symmetric multimers.

PMID- 8272428
TI  - A reduced representation of proteins for use in restraint satisfaction
      calculations.
AB  - A reduced representation of proteins has been developed for use in restraint
      satisfaction calculations with dynamic simulated annealing. Each amino acid
      residue is represented by up to four spherical virtual atoms. The virtual bonds
      and excluded volume of these atoms has been parameterized by analysis of 83
      protein structures determined at high resolution by X-ray crystallography. The
      use of the new representation in NOE distance restraint satisfaction has been
      compared with the standard all-atom representation for the determination of the
      structures of crambin, echistatin, and protein G. Using the reduced
      representation, there is a 30-fold decrease in the computer time needed for
      generating a single structure, and up to a 20-fold decrease in the time taken to
      produce an acceptable structure compared to using the all-atom representation.
      The root mean square deviation between the mean structure obtained with all-atom
      and reduced representations is between 1.5 and 1.7 A for C alpha atoms. The new
      representation is adequate for describing the "low-resolution" features of
      protein structure such as the general fold and the positions of secondary
      structure elements. It can also provide an initial structure for more detailed
      refinement with the full all-atom representation.

PMID- 8272429
TI  - Crystallization and preliminary X-ray investigation of barstar, the intracellular
      inhibitor of barnase.
AB  - Crystals of barstar, the intracellular inhibitor of the extracellular
      ribonuclease produced by Bacillus amyloliquefaciens (barnase), were obtained
      through vapor phase equilibration using the hanging drop technique. Three crystal
      forms have been characterized. Forms I and II, crystallized either in potassium
      phosphate or sodium citrate, are tetragonal; they exhibit a superstructure along
      the c-axis. Form III crystals, suitable for a high resolution structure
      determination, were grown from 55-65% ammonium sulfate. This crystal form is
      hexagonal and diffracts to at least 2 A resolution at a synchrotron radiation
      source. It belongs to the hexagonal space group P6, with unit cell dimensions a =
      b = 143.6 A, c = 35.6 A. There are four molecules of barstar in the asymmetric
      unit. X-ray data have been collected to 2.2 A Bragg spacing. The structure
      determination is underway in order to analyze conformational changes of barstar
      upon complexation with barnase.

PMID- 8272430
TI  - Growth and analysis of crystal forms of toxic shock syndrome toxin 1.
AB  - Native toxic shock syndrome toxin 1 (TSST-1) purified from Staphylococcus aureus
      has been crystallized in four different forms. The highest resolution data (2.05
      A) was collected from orthorhombic crystals belonging to the space group C222(1).
      The unit cell dimensions are a = 108.7 A, b = 177.5 A, c = 97.6 A. Rotation
      function analysis of this form indicates that there is trimer of toxin molecules
      in the asymmetric unit with a local 3-fold axis parallel to the crystallographic
      c axis. Crystals of a double mutant of TSST-1 have been grown which has a single
      molecule in the asymmetric unit and diffract to 1.9 A. The space group is P2(1)
      with unit cell parameters of a = 44.4 A, b = 34.0 A, c = 55.2 A, beta = 93.0
      degrees.

PMID- 8272431
TI  - The spatial distribution of cavitation induced acoustic emission,
      sonoluminescence and cell lysis in the field of a shock wave lithotripter.
AB  - This study examines the spatial distribution of various properties attributed to
      the cavitation field generated by a shock wave lithotripter. These properties
      include acoustic emission and sonoluminescence, which result from violent bubble
      collapse, and the degree of cell lysis in vitro, which appears to be related to
      cavitation. The acoustic emission detected with a 1 MHz, 12 cm diameter focused
      hydrophone occurs in two distinct bursts. The immediate signal is emitted from a
      small region contained within the 4 MPa peak negative pressure contour. A second,
      delayed, burst is emitted from a region extending further along the beam axis.
      The delay between these two bursts has also been mapped, and the longest delay
      occurs at positions close to the regions of maximum peak negative pressure.
      Sonoluminescence from both single and multiple shocks occurs in a broader region
      than the acoustic emission but the measurement technique does not allow time
      resolution of the signal. Cell lysis occurs in a relatively small region that
      correlates closely with the immediate acoustic emission for a shock propagating
      in a gelatine solution.

PMID- 8272432
TI  - The influence of fluid properties and pulse amplitude on bubble dynamics in the
      field of a shock wave lithotripter.
AB  - This study concerns the radial dynamics of a bubble driven by pulsed ultrasound
      of the type generated during extracorporeal shock wave lithotripsy. In
      particular, a numerical model has been used to examine the sensitivity of the
      bubble oscillations to changes in both the amplitude of the driving field and the
      physical conditions of the fluid surrounding the bubble: viscosity, surface
      tension, temperature and gas content. It is shown that, at high negative
      pressures (p- = 10 MPa) as in lithotripsy, the timing and amplitude of bubble
      collapses have a considerably reduced sensitivity to the initial bubble size and
      all fluid parameters, except gas content, compared with those expected in lower
      amplitude fields (p- = 0.2 MPa). This study indicates that, in the lithotripsy
      fields, the differences in the viscosity, surface tension and temperature of body
      fluids and the initial bubble size will have little effect on bubble dynamics
      compared with those expected in water.

PMID- 8272433
TI  - Optical imaging of shock waves produced by a high-energy electromagnetic
      transducer.
AB  - An electromagnetic acoustic transducer (EMAT) and acoustic lens have been
      constructed to provide reproducible and well characterized acoustic shock waves
      in water. The peak pressure amplitude variation for the unfocused and focused
      shock waves was found to be within +/- 5%. The focal region has been
      characterized both optically and by conventional piezoelectric pressure
      measurements. Optical investigations centre around ruby laser illuminated
      Schlieren and focused shadow imaging. The temporal resolution of the optical
      technique was determined by the ruby laser pulse length of 20 ns, giving a
      spatial resolution of 30 microns for a shock front in water.

PMID- 8272434
TI  - A comparison of colour flow imaging algorithms.
AB  - In this paper we will present and explain coherently the two main algorithms
      which are currently used in commercial colour flow imaging systems, namely the
      frequency domain based autocorrelation algorithm and the time domain based cross
      correlation algorithm. The autocorrelation algorithm is a robust optimum mean
      frequency baseband estimator, for both high and low signal to noise ratio (SNR).
      Its main disadvantage is its aliasing problem. However the cross correlation
      algorithm does not suffer from this problem, and this has been one of the main
      reasons for its development. The mathematics behind these two algorithms and the
      general data processing steps used for their implementation will be also
      presented. The subject of clutter removal filtering will be discussed and
      valuable points will be made. A practical relevant approach on how to
      discriminate between wanted blood flow related estimates and unwanted false
      estimates due to noise will be presented. On the aliasing problem of the
      autocorrelation algorithm, a promising solution known as spatial tracking of
      estimated mean frequency does exist, which will be also introduced in detail.
      Towards the end of this paper other algorithms, which are currently the subject
      of research and have potential for development, will be discussed.

PMID- 8272435
TI  - Quality assurance of ultrasound imaging instruments by monitoring the monitor.
AB  - Ultrasound quality assurance (QA) is a means of assuring the constant performance
      of an ultrasound instrument. A novel 'ultrasound image analyser' has been
      developed to allow objective, accurate and repeatable measurement of the image
      displayed on the ultrasound screen, i.e. as seen by the operator. The analyser
      uses a television camera/framestore combination to digitize and analyse this
      image. A QA scheme is described along with the procedures necessary to obtain a
      repeatable measurement of the image so that comparisons with earlier good images
      can be made. These include repositioning the camera and resetting the video
      display characteristics. The advantages of using the analyser over other methods
      are discussed. It is concluded that the analyser has distinct advantages over
      subjective image assessment methods and will be a valuable addition to current
      ultrasound QA programmes.

PMID- 8272436
TI  - Towards a protocol for measurement of maximum spatial peak temporal average
      acoustic intensity from diagnostic B mode ultrasound scanners in the field.
AB  - The Northern Regional Medical Physics Department has been involved in measurement
      of the acoustic output of diagnostic ultrasound equipment for several years. As
      the complexity of diagnostic ultrasound equipment has increased, so have the
      problems of measuring the acoustic outputs of this equipment in the field.
      Measurements made in the field are often made on unfamiliar pieces of equipment
      and under tight constraints of time. In these circumstances the magnitude and the
      conditions under which the true maximum Ispta value occurs may not always be
      found. The aim of a measurement protocol is therefore to facilitate the
      measurement of Ispta in the field, so that the measured maximum Ispta value is as
      close as possible to the 'true maximum' Ispta value. To be of practical benefit
      the protocol must be succinct and easy to use, as well as applicable to most if
      not all types of scanner. Our experience has led us to believe that this is
      possible and that the benefits of a well designed measurement protocol will far
      outweigh any disadvantages. The development of two measurement protocols is
      discussed in this paper. The time required to carry out each measurement depends
      on the number of assumptions made about the operation of the scanner in the
      protocol used. The first protocol makes very few assumptions about the operation
      of a scanner; the results from measurements made using this protocol can be used
      to assess the validity of the much larger number of assumptions made in the
      second protocol. The results from measurements on three types of scanner using
      the two protocols are presented. The results demonstrate the validity of most of
      the assumptions made by the protocols and the potential benefits of using a
      protocol for measurement of maximum Ispta in the field in terms of reduced
      measurement time and greater consistency.

PMID- 8272437
TI  - A programmable Doppler string test object.
AB  - A prototype water filled ultrasound string test object is presented for
      performance checks on Doppler ultrasound systems. The string motion produces
      realistic and reproducible Doppler wave forms on the system by means of a
      programmable stepper motor. Wave forms can be generated using a computer, and
      programmed into the device. The test object can be used to check Doppler
      calculation parameters, such as pulsatility index and resistance index, as well
      as range gate registration and wall filter function. The test object is water
      filled, and the lack of attenuation did prove to be a problem on some systems.
      The object was tested using five different duplex and colour scanners, and found
      to be sufficiently reproducible for use as a field test object for Doppler
      ultrasound machines. The device is compact and portable, making it suitable for
      checks in the field for both longterm monitoring of performance and inter-machine
      comparisons.

PMID- 8272438
TI  - Blood flow measurement by Doppler ultrasound: a question of angles.
AB  - Ultrasound Doppler equipment is widely used to estimate blood velocity and volume
      flow. Recently there has been correspondence concerning the origin of the Doppler
      shift in blood vessels. The assumption that only the movement of the target need
      be considered is challenged by the observation that Doppler shifts occur where
      there is relative motion. In blood there is unlikely to be relative motion
      between a reflecting blood corpuscle and its supporting plasma. In the simple
      case of plug flow the relative movement takes place at the vessel wall. An
      investigation is described which uses a flow rig Doppler phantom to assess what
      effect, if any, this phenomenon would have on Doppler shift results obtained by
      insonating a vessel such as the aortic arch and range gating through a curved
      section where flow velocity gradients are encountered. It has been assumed that
      if the sample volume were to lie in that part of the vessel in which the blood
      velocity vector were directly towards the probe, then an angle of 0 degrees could
      be assumed for calculations using the Doppler equation. Our results indicate that
      the observed Doppler shifts lie midway between those expected if the shift were
      to occur solely at the first moving fluid boundary and those originating only
      from scatterers within the sample volume.

PMID- 8272439
TI  - Experimental validation of predicted temperature rises in tissue-mimicking
      materials.
AB  - Increasingly, it is recognised that diagnostic ultrasound is capable of causing
      temperature rises sufficient to damage tissue. Predictions of this heating are
      often based on simplified models of both the in vivo conditions and the relevant
      physical effects. Few measurements have been made to verify these predictions,
      however, particularly for the tightly focused beams often employed in diagnosis.
      Furthermore, non-linear effects in both the acoustic field and the surrounding
      medium have largely been ignored in calculations. To provide an alternative way
      to estimate the heating, NPL has developed a measurement system to determine
      directly the temperature rise in tissue-mimicking materials. If necessary, the
      measurement results can be processed to model the effects of blood perfusion. The
      temperature is measured using thin-film thermocouples, which have essentially no
      interaction with the ultrasound or thermal fields. Measurements were made on
      transducers operating in the frequency range 2-10 MHz and with focal beam-widths
      from 1 to 3 mm. The measurements agree with theoretical predictions that use
      either the measured beam-profile or a simplified (Gaussian) model. The results
      are also compared with the standard soft-tissue models developed by the National
      Council on Radiation Protection and Measurements (NCRP) and jointly between the
      American Institute of Ultrasound in Medicine and the National Electrical
      Manufacturers Association (AIUM/NEMA). On average, the predictions of the NCRP
      formula are 15% higher than the measurements, confirming its validity as a worst
      case model. The predictions based on the AIUM/NEMA formula, however, are
      typically 30% lower than the measured values.

PMID- 8272440
TI  - Effect of blood perfusion on the ablation of liver parenchyma with high-intensity
      focused ultrasound.
AB  - This paper discusses the effect of blood perfusion on the ablation of rat liver
      tissue with high-intensity focused ultrasound (HIFU). For this study a practical
      method has been developed, in which the liver blood flow can be reduced by
      ligation of the hepatic artery and portal vein. During the treatment the rat
      liver was mobilized out of the abdomen and the blood flow was measured using both
      the radioactive microsphere method and a laser Doppler blood-flow monitor. The
      results show that the hepatic blood flow was about 23 ml/100 g min-1 via the
      hepatic artery and about 227 ml/100 g min-1 via the portal vein. The total liver
      blood flow was reduced by 98% when both the hepatic artery and portal vein were
      ligated. Comparative lesions were made on the same liver lobes of rats with both
      normal and reduced blood flow using a focused ultrasound beam of 1.7 MHz, 67-425
      W cm-2 spatially averaged focal intensity ISAL and 2-20 s exposure duration. A
      marked difference has been found between the lesion dimensions obtained with
      normal blood flow and that with reduced blood flow. For exposures at 169 W cm-2
      the lesion diameter with normal blood flow was reduced by 14% for 3 s exposure
      duration compared to that obtained with both hepatic artery and portal vein
      ligated, while the reduction was more than 20% for longer durations.

PMID- 8272441
TI  - Mapping schizophrenic negative symptoms onto measures of the patient's speech:
      set correlational analysis.
AB  - We describe a system designed to assess the speech behaviors that inform
      clinicians about their patients' negative symptoms. Measures are formed into
      scales to reflect the patient's Pausing, Speech Rate, and Dyadic Interaction with
      the interviewer. Using set correlation, we examined the associations between the
      acoustic scales and the clinician's ratings of Flat Affect, Alogia, and
      Asociality. Over half of the multivariance in the clinical scales was accounted
      for by the acoustic scales. Unique isomorphisms between the acoustic and rating
      scales were found for: Dyadic Interaction with Flat Affect; Pause Production with
      Alogia; and Rate with Asociality.

PMID- 8272442
TI  - Smooth pursuit and saccadic eye movements and Wisconsin Card Sorting Test
      performance in obsessive-compulsive disorder.
AB  - Smooth pursuit eye movements (SPEMs), voluntary saccadic eye movements (VSEMs),
      and neuropsychological test (Touluse-Pieron Test and Wisconsin Card Sorting Test)
      performance were studied in 23 patients with obsessive-compulsive disorder and 27
      age-matched normal control subjects. The patients performed more poorly than the
      control subjects on the SPEM and, to a lesser degree, VSEM measures. They also
      showed impairment on some aspects of the neuropsychological tests. No
      relationship was found between eye movement performance and neuropsychological
      impairment.

PMID- 8272443
TI  - Cellular immunity, HLA-class I antigens, and family history of psychiatric
      disorder in endogenous psychoses.
AB  - We found an increased lymphocyte proliferation after stimulation with an antigen
      "cocktail" in 49 schizophrenic patients and 37 patients suffering from affective
      psychosis, compared with 45 healthy control subjects. On the basis of this and
      other findings such as increased numbers of CD3+ and CD4+ cells, an increased
      ratio of CD4+/CD8+ cells, and a reduced level of suppressor cell activity in
      schizophrenia and endogenous depression, we investigated the influence of the
      human leukocyte antigen-Class I (HLA-A, HLA-B, HLA-C) system on the altered
      immune function and evaluated the relationship to immune function of a family
      history of psychiatric disorders. A cluster analysis of cases with regard to the
      HLA-Class I antigens was first performed in a group of 133 healthy control
      subjects, and two immunogenetically different clusters were found; then 86
      patients (49 schizophrenics, 37 affective psychoses) for whom immune functional
      data were available were assigned to the two HLA-I clusters that had been
      determined in the control subjects. Analyses of variance (ANOVAs) showed no
      differences in immune function between the two clusters. With respect to the
      cluster assignment and the family history of psychiatric diseases, a two-way
      ANOVA revealed significant differences in the lymphocyte response to the antigen
      cocktail, in the number of CD8+ cells, and in one suppressor cell assay. When
      patients were compared by ANOVA on the basis of family history of psychiatric
      disorder, patients with a positive family history showed a significantly higher
      number of CD4+ cells and a higher CD4+/CD8+ ratio. Moreover, certain HLA genes,
      especially HLA-A1, HLA-B8, HLA-B16, and HLA-C2 seemed to be related to the immune
      function and/or to the immune function and the family history.

PMID- 8272444
TI  - The amphetamine challenge test correlates with affective lability in healthy
      volunteers.
AB  - The personality dimension of mood lability may be reflected in the mood response
      to the amphetamine challenge test. To test this hypothesis, the investigators
      acutely administered oral dextroamphetamine or placebo in a double-blind fashion
      to 11 normal control subjects who were free of any psychiatric disorders.
      Increased scores on interview and self-report measures of mood change during the
      challenge test, particularly increases in depression and anxiety, positively
      correlated with scores on the Affective Lability Scale, a measure of the lifetime
      personality trait of mood lability. These findings suggest that a dysphoric
      response to amphetamine is a marker for affective lability and that it may be
      useful to study this trait in patients with personality disorders.

PMID- 8272445
TI  - Heritability of irritable impulsiveness: a study of twins reared together and
      apart.
AB  - The heritability of self-reported personality traits related to impulsiveness,
      irritability, and the inhibition of assertive or aggressive behavior was examined
      in up to 500 healthy monozygotic and dizygotic twin pairs raised together or
      apart. Two factors related to "(lack of) assertiveness/aggression" (Factor I) and
      "impulsive irritability" (Factor II) were examined using traditional and model
      fitting procedures. Results of model-fitting procedures were consistent with a
      genetic, but not a shared environmental, influence for both factors. Further
      analysis suggested a nonadditive genetic influence for Factor II and an additive
      influence for Factor I. Bivariate model-fitting analyses suggest that self
      reported "irritable impulsiveness" and "(lack of) assertiveness/aggressiveness"
      show substantial, though different, genetic influences.

PMID- 8272446
TI  - A family study of self-reported personality traits and DSM-III-R personality
      disorders.
AB  - Personality traits and DSM-III-R personality disorders of first-degree relatives
      of patients with psychoses were studied using the NEO Five-Factor Inventory (NEO
      FFI) and the Personality Diagnostic Questionnaire-Revised (PDQ-R), two self
      report instruments. The relatives were compared on their scores for the five
      personality factors in the NEO-FFI, the prevalence of individual DSM-III-R
      personality disorders, and their scores for each personality disorder scale in
      the PDQ-R. The results suggest that there is no difference in personality traits
      and prevalence of personality disorders, including schizophrenia spectrum
      disorders, when relatives of patients with schizophrenia, bipolar disorder, and
      major depression are compared to each other. Relatives of patients with "atypical
      psychosis," psychotic disorders that do not meet DSM-III-R criteria for any
      specific nonorganic psychotic disorder, may be a distinctive group.

PMID- 8272447
TI  - Neuropsychiatric impairment in impulsive personality disorders.
AB  - It has been suggested that impulsivity and aggression are associated with
      neuropsychiatric impairment. Neurological soft signs may be a useful marker of
      nonspecific brain damage, and may therefore be increased in impulsive and
      aggressive patients compared with normal control subjects. A structured
      examination was used to evaluate neurological soft signs in 28 patients with
      personality disorders characterized by impulsivity and 28 healthy control
      subjects. All of the patients met DSM-III-R criteria for borderline personality
      disorder, and 10 also met criteria for antisocial personality disorder. All
      patients were questioned about past history of physical aggression, and a subset
      of 18 patients underwent neuropsychological testing with a select battery. Left
      sided neurological soft signs were significantly increased in patients compared
      with normal control subjects. Patients with a history of aggression, however, had
      significantly more right-sided neurological soft signs than those without a
      history of aggression. Increased neurological soft signs were associated with
      impairment on the Wisconsin Card Sort, a test of frontal lobe executive function.
      Specific neuropsychiatric abnormalities, such as lateralized neurological soft
      signs and associated impairment on select neuropsychological tests, may be
      present in patients with personality disorders characterized by impulsivity.

PMID- 8272448
TI  - Prevalence and characteristics of sadistic personality disorder in an outpatient
      veterans population.
AB  - This study is designed to examine the prevalence, demographics, and the Axis I
      and Axis II diagnoses of sadistic personality disorder (SPD) in a previously
      unexamined population (outpatient veterans). It also represents the first attempt
      to examine the family history of those with SPD. Standardized methods were used
      to select 144 nonpsychotic subjects from a veterans psychiatric outpatient
      clinic. The population was then divided into three groups: those with SPD, those
      without SPD but with antisocial personality disorder or traits, and those with no
      Axis II disorders. A fourth group consisted of 28 control veterans without
      psychopathology. Subjects with SPD tended to be younger and to have lower scores
      on the Global Assessment Scale than did clinical control subjects without
      personality disorders; they also had significantly more bipolar and panic
      disorder than were found in the antisocial traits group. High levels of
      depression and alcohol dependence were also present. SPD traits correlated with
      DSM-III-R dramatic cluster, compulsive, passive-aggressive, and self-defeating
      personality disorders. The SPD group could be distinguished from other groups on
      the basis of family history. It was concluded that sadistic personality traits
      and disorders are prevalent (8.1%), associated with reduced functioning, and may
      have specific associations with certain Axis I and Axis II disorders. It is
      possible that they have a distinct familial pattern.

PMID- 8272449
TI  - Sleep and "sundowning" in nursing home patients with dementia.
AB  - "Sundowning," a term that is sometimes equated with sleep disturbance or
      nocturnal delirium in dementia, is a poorly understood psychiatric phenomenon. In
      this study, we performed systematic, temporally specific, behavioral observations
      of nine profoundly demented nursing home patients 4 times an hour over a 12-hour
      period (1300 to 0100h) to determine whether their agitation was more likely to
      occur at a particular time of day. Results indicated only equivocal evidence that
      agitation was any worse nocturnally or during the time near sunset, thus raising
      the possibility that at least some components of sundowning may reflect
      disruptive behaviors occurring with identical frequency throughout the day but
      with differential impact upon nursing staff. Additional data indicated that
      awakening from sleep during darkness was also associated with agitation. A final
      result was a trend indicating the apparent worsening of agitation seasonally
      (greater agitation during winter), which may suggest involvement of the circadian
      timing system.

PMID- 8272450
TI  - Computed tomography and neurological soft signs in obsessive-compulsive disorder.
AB  - Computed tomography was used to compare the following three groups: obsessive
      compulsive disorder (OCD) patients with high scores on a soft neurological sign
      examination, OCD patients with low soft neurological sign scores, and control
      subjects. Neuranatomical structures were measured using quantitative volumetric
      analysis. OCD patients with high soft sign scores had significantly increased
      ventricular volumes compared with OCD patients with low soft sign scores and
      control subjects. Caudate and lenticular nucleus volumes did not differ between
      groups.

PMID- 8272451
TI  - Dementia of the Alzheimer type: effects on the spontaneous EEG described by
      dipole sources.
AB  - The present study on brain electrical activity in healthy subjects (n = 35) and
      patients suffering from dementia of the Alzheimer type (DAT; n = 35) used Fast
      Fourier Transformation-dipole approximation to quantify differences between the
      two groups. DAT patients showed a shift of alpha and beta activity toward frontal
      brain regions. The amount of this shift correlated with the degree of dementia.
      The relative distribution of magnitude of activity between the frequency bands
      differed between DAT patients and control subjects. DAT patients had higher
      magnitudes in the slow frequency range, correlating with the severity of
      dementia, and lower ones in the alpha and beta range compared with findings in
      age-matched control subjects.

PMID- 8272452
TI  - Findings of electroencephalographic brain mapping in mild to moderate dementia of
      the Alzheimer type during resting, motor, and music-perception conditions.
AB  - Sixteen-channel electroencephalographic (EEG) brain mapping studies were carried
      out under resting conditions in 41 patients with mild to moderate dementia of the
      Alzheimer type, diagnosed according to DSM-III-R criteria. The patients showed
      diffuse patterns of EEG slowing, as known from the literature. They showed
      increases of theta power in large bilateral brain areas and bitemporal increases
      of delta power as compared with both age-matched and younger control subjects. In
      addition, the patients had increased beta activity in comparison with the younger
      control group, but not with the age-matched control subjects. Functional brain
      mapping revealed decreases of EEG power during manual-motor and music-perception
      tasks in delta frequencies for patients, which was not seen in either of the two
      control groups. All frequency bands revealed major gender-related differences in
      EEG activity, which should receive more attention in future research.

PMID- 8272453
TI  - Regional cerebral blood flow during the Wisconsin Card Sorting Test in normal
      subjects studied by xenon-133 dynamic SPECT: comparison of absolute values,
      percent distribution values, and covariance analysis.
AB  - We studied regional cerebral blood flow (rCBF) by xenon-133 dynamic single photon
      emission computed tomography (SPECT) in 17 normal volunteers who were performing
      the Wisconsin Card Sorting Test (WCST), a task that is particularly sensitive to
      disturbance of the prefrontal cortex, and a simple matching-to-sample task (BAR)
      as a sensorimotor control. Three methods for statistical analysis of regional
      "subtraction" data were used: absolute rCBF values, percent distribution values,
      and means adjusted for global CBF changes (covariance analysis). The absolute
      values had high variance, due to the combination of interindividual differences
      in global flow and intra-individual variation, and showed no statistically
      significant regional changes. This variation was greatly reduced by percent
      values and covariance analysis, which had quite similar outcomes. With both
      methods, significant increases of rCBF during the WCST as compared with the BAR
      were seen in the right anterior dorsolateral prefrontal and left occipital
      cortices, and reduction of rCBF in the left pararolandic region. Moreover,
      significant correlations with performance were found in the medial regions of the
      frontal lobes, with opposite trends for the right and left hemisphere. The
      posterior dorsolateral prefrontal region showed a negative correlation with
      sensory-motor frequency, an index related to the task's difficulty. These results
      are consistent with previous findings using other rCBF techniques and confirm the
      statistical advantage of normalization and covariance methods, which yield
      practically identical results, at least in this analysis based on regions of
      interest.

PMID- 8272454
TI  - Increased prevalence of cavum septum pellucidum in schizophrenia.
AB  - A previous report that the presence of a cavum septum pellucidum was
      significantly more common in schizophrenic patients than in control subjects
      (DeGreef et al., 1992) stimulated the present study of an independent but similar
      population of first admission schizophrenic patients. A high prevalence of this
      developmental anomaly (44.8%) was found in the patients (n = 85), although it
      could also be detected in 29.8% of similarly aged control subjects (n = 47). This
      finding was not associated with corpus callosum, ventricular, or temporal lobe
      size or asymmetries.

PMID- 8272456
TI  - Hide-and-seek in the playroom: on object loss and transference in child
      treatment.

PMID- 8272455
TI  - The peek-a-boo game.

PMID- 8272457
TI  - To be or not to be separate: the meaning of hide-and-seek in forming internal
      representations.

PMID- 8272458
TI  - From hallucination to dream: from evacuation to the tolerability of pain in the
      analysis of a preadolescent.

PMID- 8272459
TI  - Homoerotic body language in Dostoevsky.

PMID- 8272460
TI  - Psychoanalysis in Czechoslovakia.

PMID- 8272461
TI  - Freud and Dostoevsky.

PMID- 8272462
TI  - On the therapist's disability: opportunities for resolution of obstructed
      mourning in the transference.

PMID- 8272463
TI  - Psychological impact of biculturalism: evidence and theory.
AB  - A vital step in the development of an equal partnership for minorities in the
      academic, social, and economic life of the United States involves moving away
      from assumptions of the linear model of cultural acquisition. In this article we
      review the literature on the psychological impact of being bicultural.
      Assimilation, acculturation, alternation, multicultural, and fusion models that
      have been used to describe the psychological processes, social experiences, and
      individual challenges and obstacles of being bicultural are reviewed and
      summarized for their contributions and implications for investigations of the
      psychological impact of biculturalism. Emphasis is given to the alternation
      model, which posits that an individual is able to gain competence within 2
      cultures without losing his or her cultural identity or having to choose one
      culture over the other. Finally, a hypothetical model outlining the dimensions of
      bicultural competence is presented.

PMID- 8272464
TI  - Etiology of child maltreatment: a developmental-ecological analysis.
AB  - This article applies a developmental-ecological perspective to the question of
      the etiology of physical child abuse and neglect by organizing the paper around a
      variety of "contexts of maltreatment." The roles of parent and child
      characteristics and processes are considered ("developmental context"), including
      an examination of intergenerational transmission. The "immediate interactional
      context" of maltreatment, which focuses on the parenting and parent-child
      interactional processes associated with abuse and neglect, is analyzed. Finally,
      the "broader context" is discussed with 3 specific subsections dealing with the
      community, cultural, and evolutionary contexts of child maltreatment.
      Implications for intervention are considered and future research directions are
      outlined.

PMID- 8272465
TI  - Human contingency judgments: rule based or associative?
AB  - The study of the mechanism that detects the contingency between events, in both
      humans and nonhuman animals, is a matter of considerable research activity. Two
      broad categories of explanations of the acquisition of contingency information
      have received extensive evaluation: rule-based models and associative models.
      This article assess the two categories of models for human contingency judgments.
      The data reveal systematic departures in contingency judgments from the
      predictions of rule-based models. Recent studies indicate that a contiguity model
      of Pavlovian conditioning is a useful heuristic for conceptualizing human
      contingency judgments.

PMID- 8272466
TI  - An appraisal-disruption model of alcohol's effects on stress responses in social
      drinkers.
AB  - This article reviews the effects of alcohol on stress responses among social
      drinkers. Despite considerable research, the relationship between alcohol and
      stress has remained unclear. An appraisal-disruption model of alcohol's effects
      on stress responses is proposed, which attempts to integrate many divergent
      findings. According to this model, alcohol disrupts initial appraisal of
      stressful information by constraining the spread of activation of associated
      information previously established in long-term memory. The conditions under
      which such disruption is likely to occur are outlined. Evidence relevant to each
      of the model's propositions is considered. It is concluded that the appraisal
      disruption model provides a framework for integrating many of the findings from
      past investigations. Theoretical issues pertinent to the model are addressed.

PMID- 8272467
TI  - Drug-induced amnesia: implications for cognitive neuropsychological
      investigations of memory.
AB  - Studies of drug effects on memory represent a large body of literature that, for
      the most part, has not had an impact on psychological theories of memory and
      amnesia produced by cognitive psychologists, who tend to theorize independently
      of information about the brain. Recently, however, there has been a movement
      toward cognitive neuropsychological approaches to memory in which theorists have
      begun to consider, and even focus on, neuroanatomical realities. This approach
      currently relies on data from organic amnesic patients and normal Ss. This
      article suggests that studies of drug-induced amnesia complement these current
      lines of investigation and therefore merit consideration from cognitive
      neuropsychologists interested in memory. To this end, the drugs and memory
      literature is reviewed, and its potential relationship with more mainstream
      cognitive neuropsychology is discussed.

PMID- 8272468
TI  - Methods for dealing with reaction time outliers.
AB  - The effect of outliers on reaction time analyses is evaluated. The first section
      assesses the power of different methods of minimizing the effect of outliers on
      analysis of variance (ANOVA) and makes recommendations about the use of
      transformations and cutoffs. The second section examines the effect of outliers
      and cutoffs on different measures of location, spread, and shape and concludes
      using quantitative examples that robust measures are much less affected by
      outliers and cutoffs than measures based on moments. The third section examines
      fitting explicit distribution functions as a way of recovering means and standard
      deviations and concludes that unless fitting the distribution function is used as
      a model of distribution shape, the method is probably not worth routine use.

PMID- 8272469
TI  - The use of causal indicators in covariance structure models: some practical
      issues.
AB  - In conventional representations of covariance structure models, indicators are
      defined as linear functions of latent variables, plus error. In an alternative
      representation, constructs can be defined as linear functions of their
      indicators, called causal indicators, plus an error term. Such constructs are not
      latent variables but composite variables, and they have no indicators in the
      conventional sense. The presence of composite variables in a model can, in some
      situations, result in problems with identification of model parameters. Also, the
      use of causal indicators can produce models that imply zero correlation among
      many measured variables, a problem resolved only by the inclusion of a
      potentially large number of additional parameters. These phenomena are
      demonstrated with an example, and general principles underlying them are
      discussed. Remedies are described so as to allow for the evaluation of models
      that contain causal indicators.

PMID- 8272470
TI  - Confirmatory factor analysis and item response theory: two approaches for
      exploring measurement invariance.
AB  - This study investigated the utility of confirmatory factor analysis (CFA) and
      item response theory (IRT) models for testing the comparability of psychological
      measurements. Both procedures were used to investigate whether mood ratings
      collected in Minnesota and China were comparable. Several issues were addressed.
      The first issue was that of establishing a common measurement scale across
      groups, which involves full or partial measurement invariance of trait
      indicators. It is shown that using CFA or IRT models, test items that function
      differentially as trait indicators across groups need not interfere with
      comparing examinees on the same trait dimension. Second, the issue of model fit
      was addressed. It is proposed that person-fit statistics be used to judge the
      practical fit of IRT models. Finally, topics for future research are suggested.

PMID- 8272471
TI  - The Hamilton disorders.

PMID- 8272472
TI  - Behavioral psychotherapy applications in the medically ill.
AB  - Behavioral psychotherapy may promote physical health and treat some behavior
      linked medical conditions. Prevention of risk factors, and relapse through self
      management, the development of a healthy life-style and the possibility to use
      its technology in the community at a relatively low cost are emphasized.
      Controlled studies suggest its effectiveness in cardiovascular diseases,
      headaches, stuttering, alcoholism, pain and bulimia nervosa. Cancer,
      psychoneuroimmunology and AIDS are under investigation. Psychogeriatrics in an
      emerging field. More basic research is needed to establish firmly the theoretical
      underpinnings of behavioral medicine including a cognitive component and to
      extend its practice to medical staff.

PMID- 8272473
TI  - Psycho-oncology: psychological well-being as one component of quality of life.
AB  - This review deals with the issues of quality of life and psychological well-being
      in cancer patients, with particular reference to the role of psychiatry in the
      oncology setting. The prevalence of psychiatric diagnoses as a measure of
      psychological well-being, the prediction of psychological well-being, the
      interactions between physical and psychological factors, and the impact of
      psychosomatic intervention on quality of life in cancer patients, are discussed.

PMID- 8272474
TI  - Review of psychosomatic aspects of cardiovascular disease.
AB  - This review deals with the clinically most relevant psychosomatic aspects of
      cardiovascular disease. Smoking cessation, the role of physical activity in the
      prevention and rehabilitation of cardiac disease, the relationship of cholesterol
      to behavior, depression and heart disease, the pharmacotherapy of depression in
      this specific patient population, the psychiatric risk factors for coronary
      artery disease, and the treatment of hostility, stress and type A behavior are
      discussed.

PMID- 8272476
TI  - Drug use and somatic illnesses with psychological component: a nation-wide survey
      among adolescents and adults in Greece.
AB  - A cross-sectional home survey on drug use, mental health, somatic illnesses and
      psychosocial issues was carried out with a nation-wide multi-stage probability
      sample of 4,292 persons aged 12-17, 18-24 and 25-64. This article aims at
      investigating the relationship of specific categories of somatic illnesses with a
      psychological component to the use of licit and illicit drugs. For the purpose of
      analysis the total sample was divided into three mutually exclusive groups: group
      A included respondents who have reported illicit drug use 1-3 or more times in
      their lives; group B comprised respondents who have reported the use of licit
      psychotropic drugs 3 or more times in their lives; group C included non-user
      respondents. A higher proportion of respondents of groups A and B of both sexes
      in all three age strata reported the presence of a specific somatic illness such
      as bronchial asthma, essential hypertension, peptic ulcer, irritable bowel
      syndrome, rheumatoid arthritis, dermatitis or eczema, in comparison to group C
      (non-user) respondents. This difference was greater in the adolescent group 12-17
      years of age. Possible explanations of the association between somatic illness
      with a psychological component and drug use are discussed.

PMID- 8272475
TI  - Association of cutaneous mast cells and sensory nerves with psychic stress in
      psoriasis.
AB  - Association of stress with psoriatic skin symptoms was studied in 13 patients
      with psoriasis by dividing the patients into low- and high-stress groups based on
      their clinical examination and answers to three questionnaires (General Health
      Questionnaire, a somatization scale, and a life change questionnaire). This study
      focused on skin mast cells and sensory nerves which are the principal components
      in neurogenic inflammation. Mast cells were stained enzyme-histochemically for
      tryptase and chymase, and neuropeptides substance P (SP), vasoactive intestinal
      peptide (VIP), and calcitonin gene-related peptide (CGRP) were demonstrated
      immunohistochemically. Compared to the low-stress group (n = 7), the patients in
      the high-stress group (n = 6) had more severe skin and joint symptoms.
      Furthermore, mast cells positive for chymase activity were prominently reduced,
      but tryptase-positive mast cells only slightly decreased in the lesional skin of
      the high-stress group. A similar tendency was also observed in the nonlesional
      skin. In the papillary dermis of the lesional skin, both VIP- and CGRP
      immunoreactive nerves could be observed in the high-stress group whereas in the
      low-stress group these nerve fibers were hardly visible in the corresponding
      area. No association of SP with stress was observed. This study suggests that
      psychic stress is associated with exacerbation of psoriasis, and stress may
      induce alterations in the psoriatic lesions by increasing the neuropeptide
      content with a concomitant decrease in the activity of neuropeptide-degrading
      enzymes, especially mast cell chymase.

PMID- 8272477
TI  - Hemispheric activation, affective judgments, and pain perception.
AB  - This study utilized a unique contact lens method to examine the influence of
      right hemisphere processing on affective judgments and pain perception. Under
      conditions of unilateral visual stimulation, participants completed affective
      ratings of films and underwent a cold pressor pain task. The goal was to examine
      differences in affective judgments of films projected to one or the other
      hemisphere and to examine the influence of this unilateral visual stimulation on
      pain sensitivity. The results failed to replicate a previous finding of
      differential affective judgments under conditions of right and left visual
      stimulation. Nonetheless, in female subjects, unilateral visual stimulation was
      significantly associated with pain lateralization. This finding is discussed in
      terms of attentional processes in pain perception and limitations of the current
      lens design.

PMID- 8272478
TI  - Medical health and emotional effects of art stimulation in old age. A controlled
      intervention study concerning the effects of visual stimulation provided in the
      form of pictures.
AB  - The present article reports on a controlled intervention study of the effects of
      a nondirected use of pictures as a possible modality for improving well-being in
      elderly women. Works of art were chosen for the individual taste pattern on the
      basis of psychological and art scientific research on aesthetic reactions to and
      perception of art. Participants were randomly allocated either to the
      intervention (n = 20) or to the control (n = 20) group. Participants in both
      groups had the same amount of social contact with and attention from the
      experimenter. The difference between the groups indicated improved well-being in
      the intervention group, an improvement not seen in the control group. The
      quantitative analyses of the results reveal a significant improvement of the
      positive mood parameters happiness, peacefulness, satisfaction and calmness and
      the negative parameters low-spirited, unhappy and sad. Systolic blood pressure
      decreased and an improvement was seen in the subjects' medical health status with
      regard to reported dizziness, fatigue, pain and use of laxatives.

PMID- 8272479
TI  - Psychiatric and psychometric issues in acne excoriee.
AB  - Psychiatric and psychometric issues were assessed in 12 acne excoriee patients.
      Two patients exhibited a DSM-III-R dysthymia and 2 patients a DSM-III-R
      personality disorder, which were considered as associated comorbidities. Most
      patients reported concern for being unattractive and a compulsive urge to
      manipulate their skin. However, 8 out 12 patients did not fulfill criteria for
      any DSM-III-R disorder. In particular, we could not find evidence for the
      assumption of underlying obsessive-compulsive disorders or body image disorders
      in acne excoriee.

PMID- 8272480
TI  - Alexithymia--state and trait.

PMID- 8272481
TI  - [Morbidity during the XVI Central American and Caribbean Games: Puerto Rican
      delegation, Mexico 1990].
AB  - The health services offered to the Puerto Rican Delegation during the XVI Central
      American and Caribbean Sports Games in Mexico in 1990 included: medical, dental
      and psychological assistance, physical therapy and services on the playing field.
      From the consultation sheets completed during the Games we obtained information
      about the use of these services. The 336 members of the Puerto Rico Delegation in
      the village at Mexico City had 1,838 encounters with the health team. Of these,
      991 were medical consults, 55 group therapies, 466 physical therapy sessions and
      326 encounters in the sports venues. Among the encounters for medical evaluation
      the most frequent problems were athletic injuries (318; 32.1%), respiratory
      problems (240; 24.2%), gastrointestinal conditions (126; 12.7%) and dental
      services (119; 12.0%). The most frequent athletic injuries were first degree
      strains (83; 26.1%), tendinitis (56; 17.6%), contusions (42; 13.2%), myositis
      (40; 12.6%) and first degree sprains (28; 8.8%). The health problems found were
      diversed and in the majority of cases mild in character, which can be attend by
      adequately trained on sports health primary health professionals.

PMID- 8272482
TI  - [Menarche, menstrual and sociodemographic characteristics of Puerto Rican female
      athletes in the XV and XVI Central American and Caribbean Games].
AB  - This investigation described maturation, menstrual and socio-demographic
      characteristics of 65 Puerto Rican women athletes that were interviewed during
      the XVI Central American and Caribbean Games (CACG), Mexico City in 1990. The
      results were compared with those of Puerto Rican women athletes (n = 52) at the
      XV CACG, Santiago Dominican Republic, 1986. The quantitative variables (age, age
      at initiation of training, years of training, age at menarche, birth order, and
      family size) were not statistically different (t-independent, p > or = 0.05). The
      observed frequencies for the qualitative variables (menstrual characteristics,
      degree of certainty in the recall of age of menarche, use of oral contraceptives,
      and marital status) were very similar. IN CONCLUSION: the women at the XVI CAC in
      Mexico demonstrated similar maturational, menstrual and socio-demographic
      characteristics to the those athletes evaluated four years earlier in Santiago
      and based on their long history of training, both samples were representative of
      athletically mature athletes. The findings were very similar to those reported
      for olympic athletes and such data expands the available information on Puerto
      Rican women athletes.

PMID- 8272483
TI  - Effect of heat-shock on rhesus monkey lymphocytes and IL-2-dependent cells.
AB  - Treatment of Rhesus monkey peripheral blood lymphocytes and IL-2 dependent cell
      lines with heat prior to incubation with mitogens or IL-2, respectively, induces
      significant cell changes at the nuclear level, detected by DNA staining with
      Vindelov's propidium iodide and the simultaneous measurement of its red
      fluorescence and 90 degrees light scatter. These changes are an increase in their
      nuclear granularity and in apparently fragmented DNA which shows less
      fluorescence intensity than DNA from nuclei in the G0G1 phase, a phenomenon
      suggestive of apoptosis. Treated cells also show an increased number of nuclei in
      G1 or early S phase, with a reduction in those reaching the G2 or M phases. After
      heat-shock treatment, CTLL-2 cells show an increase in their response to low
      doses of recombinant IL-2 and an impaired ability to proliferate at higher IL-2
      concentrations. These results provide further evidence for the regulatory role of
      stress-induced events.

PMID- 8272484
TI  - Colorectal carcinoma: a pathologic and immunopathologic study.
AB  - Lewis-related blood group antigens are carbohydrate determinants carried on
      surface glycoproteins and glycolipids of erythrocytes and some epithelial cells.
      Their expressions in colorectal mucosa has been considered either as a marker of
      differentiation antigens or of tumor associated antigens. We prospectively
      studied Lewis-related blood group antigens in patients undergoing colectomy for
      colonic adenocarcinoma. Immunohematological studies were performed on
      preoperative blood samples and ABO and Lewis blood groups were determined. Tissue
      samples were obtained from the adenocarcinoma and from the adjacent non
      neoplastic mucosa. The degree of tumor differentiation (grade of the tumor) was
      analyzed on hematoxylin and eosin stained slides. Immunoperoxidase staining was
      performed using antibodies against A, B, Le(a), Le(b), Le(x), and Le(y) antigens.
      The staining results of the colonic carcinoma were compared with those of the non
      neoplastic mucosa and with the patient's red blood cell Lewis phenotype. A total
      of 22 patients were studied, 12 males and 10 females, with an average age of 64
      +/- 12 years. There were 12 modified Dukes B and 10 modified Dukes C carcinomas.
      Le(a), a marker of differentiation antigens, was expressed in the non-neoplastic
      mucosa of 82% of the specimens. Le(y), a marker of tumor associated antigens, was
      detected in 77% of the carcinomas while expressed only in 18% of the adjacent non
      neoplastic mucosa. Le(x), supposedly a marker for tumor aggressiveness, was found
      in 55% of the carcinomas. However, it was virtually absent in the five carcinomas
      which did not invade the pericolic tissues.

PMID- 8272485
TI  - Response to treatment and recurrence of dermatomycosis in patients with diabetes.
AB  - Thirteen diabetic and sixteen control patients with skin infections with
      dermatophytes and Candida albicans were evaluated for the response to treatment
      and the recurrence of the condition. Culture-proven infections of these organisms
      were treated with a topical antifungal cream (oxiconazole nitrate) for 30 days.
      There was no difference in response to treatment between the two groups. Nine
      diabetic and ten control patients were re-evaluated three months after finishing
      the treatment. Four of the nine diabetic patients (44%) and one of the ten
      control patients (10% had evidence of recurrence. Dermatophytic skin infections
      in diabetic patients seem to respond adequately to topical treatment, however,
      recurrences appear to be frequent.

PMID- 8272486
TI  - Hookworm disease: Puerto Rico's secret killer.
AB  - Drs. Bailey Ashford and Pedro Gutierrez, with the economic aid of the United
      States and Puerto Rican governments, were able to implement a program to reduce
      the incidence of hookworm infestations in Puerto Rico during the turn of the
      century. The program was conducted in three phases. The first phase consisted of
      evaluating the prevalence of infestations among the population. The second phase
      was concerned with treating patients and reducing further infestations. The last
      phase of the program was the implementation of prevention programs whose goals
      were to educate the population on the mechanisms of contaminations and to help
      implement improvements in the waste disposal systems so as to reduce the exposure
      to contaminated soil. The programs greatly improved the level of health of many
      Puerto Ricans. The incidence of hookworm infestations was reduced from 90% to 15%
      among members of the population. The program obtained world-wide recognition and
      serves as a model for similar programs.

PMID- 8272487
TI  - [The academic medical center: a teaching-health care model for changes in health
      care delivery].

PMID- 8272488
TI  - HIV risk factors among Puerto Rican youth in drug treatment.
AB  - A cross-section of 250 youngsters enrolled in drug treatment programs in Puerto
      Rico were surveyed in 1991. Even though the surveyed youngsters are not
      intravenous drug users it was found that they have a high prevalence of behaviors
      considered by the Centers for Diseases Control as increasing the risk of HIV
      infection in youth. These behaviors include frequent experimentation with non-IV
      drugs, early onset of sexual behaviors (mean = 13.5 years) and drug use (mean =
      13.8 years), and a high number of sexual partners (mean = 3.13) reported for the
      year preceding the interview. Infrequent use of contraceptives and condoms and
      ineffective practices to prevent STD/HIV were also reported. This subgroup of
      youngsters in drug treatment centers can be defined as a high risk group in need
      of HIV infection prevention services.

PMID- 8272489
TI  - Attitudinal change: a necessary ingredient for dental schools.

PMID- 8272490
TI  - Resective surgery: an esthetic application.
AB  - The esthetic influence of gingival architecture on symmetry and tooth length as
      they relate to the "smile line" can be altered through periodontal surgical
      techniques. An internal bevel gingivectomy can be utilized, with some
      modifications in technique, to increase the beauty of a smile. The practitioner
      can influence the appearance of the smile by correcting tooth length problems as
      they relate to upper lip line and correction of right-to-left asymmetries. The
      surgical techniques are described in detail for various clinical situations.

PMID- 8272491
TI  - The use of sterile versus nonsterile gloves during out-patient exodontia.
AB  - One hundred twenty-four patients who showed no clinical evidence of acute
      infection, were not taking antibiotics, and were to undergo routine removal of
      erupted teeth were studied. Patients were alternately assigned to surgeons who
      were wearing sterile or nonsterile, but clean, gloves. Surgery was performed in
      the usual manner and no postoperative antibiotics were prescribed. None of the
      patients was found to be infected postoperatively. Results of this prospective
      study suggest that routine exodontia can be safely performed by a surgeon wearing
      nonsterile, but surgically clean, gloves without increasing the risk of
      postoperative infection.

PMID- 8272492
TI  - Pulpal anesthesia from an application of a eutectic topical anesthetic.
AB  - A new topical anesthetic agent, EMLA cream 5%, was investigated to determine if
      long application times could produce a degree of pulpal anesthesia. Thirteen
      subjects underwent testing in a double-blind manner. Pulpal anesthesia was
      assessed by electrical pulp testing. After the cream was applied for 15 to 30
      minutes, 92% (12/13) of subjects reported no pain to the maximum setting of the
      pulp tester (300 V). The results of this study suggest EMLA cream has potential
      application in restorative dentistry and deserves further investigation.

PMID- 8272493
TI  - A comparative analysis of techniques of restoring cervical lesions.
AB  - There are several methods of restoring cervical abrasion or erosion lesions,
      including the use of composite resin, glass-ionomer cement, or a combination of
      these materials. This paper reports the effectiveness of three different
      materials and techniques in restoring cervical lesions, using marginal leakage as
      the means of comparison. Wedge-shaped cervical cavities were prepared so that the
      gingival cavosurface margin of each cavity involved dentin. Half of the specimens
      in each group were thermocycled. Differences in marginal leakage were more
      pronounced at the gingival margin. There was no significant difference between
      the leakage of thermocycled and nonthermocycled specimens. Microleakage can be
      expected to be minimal in cavities restored with the "sandwich" technique, in
      which a glass-ionomer cement liner and composite resin restorative material are
      placed.

PMID- 8272494
TI  - Restoration of Class II carious lesions in primary molars using light-hardening
      glass-ionomer-resin cement.
AB  - Light-hardening glass-ionomer-resin restorative cement was introduced in 1992.
      Besides having the advantage of rapid initial hardening by application of visible
      light, the new formulations have better physical properties than do self
      hardening glass-ionomer restorative materials. This article documents use of one
      such cement for restoration of Class II carious lesions in primary molars. The
      rationale for use of the new cement is reviewed.

PMID- 8272495
TI  - The oral blue nevus in children: a case report.
AB  - The intraoral blue nevus is a benign, relatively rare lesion that usually occurs
      in adults and most often in women. The reported case is interesting because the
      patient was only 11 years old. The lesion, located in the hard palate, was
      surgically removed. The specimen was sent for histologic examination, resulting
      in the final diagnosis of common blue nevus.

PMID- 8272496
TI  - The dentinal surface: its influence on dentinal adhesion. Part III.
AB  - This final paper in a series of three uses transmission and scanning electron
      microscopy to compare the category III dentinal adhesive systems--those with
      shear bond strength values near or exceeding 17 MPa. Contemporary commercial
      dentinal adhesive systems such as Superbond and Scotchbond Multi-Purpose, chosen
      for their varied chemical pretreatments, are contrasted; a contemporary
      commercial system (Prisma Universal Bond 3) with characteristics of category I
      and II dentinal adhesives is also included for comparison. The shear bond
      strength values attained with most category III systems are high enough to cause
      cohesive failure of the dentin during bond strength testing. This result is
      attributed to a combination of factors that include effective wetting and
      penetration of the prepared dentinal surface as well as a tendency to leave
      collagen fibers at the adhesive-dentin interface in an apparently structurally
      intact state.

PMID- 8272498
TI  - Much ado about resin.

PMID- 8272497
TI  - The marginal adaptation of four different bonding agents in Class II composite
      resin restorations applied in bulk or in two increments.
AB  - Class II cavities with two retention grooves at the cervical wall, situated at
      the cemento-enamel junction, were restored with Palfique Light Cured composite
      resin and one of four different bonding agents and one of two composite resin
      application techniques. In 80 restorations, any gap present was disclosed by the
      penetration of a fluorescent resin into the air-filled gap. In another 80
      restorations a toluidine blue solution was used to reveal gaps. Tokuso Light Bond
      and Superbond C&B had poor marginal adaptation: gap formation was observed in
      90.0% and 57.5% of those restorations, respectively. In contrast, All-Bond had a
      20.0% rate and Superbond D-liner had a 12.5% rate of restorations with failures,
      represented by very thin gaps in the outer part of the cervical wall. Bulk
      application of the composite resin material and light curing from the cervical
      and axial walls through a plastic matrix strip gave results comparable to those
      of a two-stage horizontal application technique with light curing from the
      occlusal area and a metal matrix band.

PMID- 8272499
TI  - Dentin: microstructure and characterization.
AB  - Dentin consists of several identifiable structures: tubules with cell processes
      and fluid; highly mineralized peritubular dentin; and intertubular dentin
      consisting mainly of collagen and deposited apatite. The structural organization
      and microstructural variations reflect formative influences, such as tooth size
      and shape, and alterations caused by age, insult, and disease. However, details
      of structure-chemistry-property relationships for this anisotropic biologic
      composite are limited. Materials scientists are focusing on an array of new
      spectroscopic, analytical, and imaging techniques that are yielding improved
      understanding of structural variations and their dependence on specimen
      preparation, tooth type, location, storage conditions, and chemical and physical
      modifications. Such studies should lead to the major refinements in structure
      properties models for dentin that are required for continued advances in dental
      composite resins and adhesives.

PMID- 8272500
TI  - Permeability of dentin to adhesive agents.
AB  - The permeability of dentin to adhesive agents is of crucial importance in
      obtaining good dentinal bonding. In those systems that remove the smear layer,
      the opportunity exists for resin to infiltrate both tubules and intertubular
      dentin. Resin penetration into tubules can effectively seal the tubules and can
      contribute to bond strength if the resin bonds to the tubule wall. Resin
      infiltration into intertubular dentin can only occur if the mineral phase of
      dentin is removed by acidic conditioners or chelators. This is more easily
      accomplished in fractured dentin than in smear layer-covered dentin because of
      the residual collagen debris that remains on the surface following acid etching
      of smear layers. The channels for resin infiltration are the perifibrillar spaces
      created around the collagen fibers of dentin following removal of apatite mineral
      by acids. The diffusion of adhesive resins through these narrow, tortuous, long
      channels in 1 to 2 minutes offers a number of challenges that require further
      research.

PMID- 8272501
TI  - Adhesives and nonshrinking dental resins of the future.
AB  - Much attention has been directed toward producing dentinal adhesives that
      withstand the forces involved during polymerization shrinkage of composite
      resins. Studies have shown that an effective dentin-adhesive bond depends on the
      wetting and penetration characteristics of the dentinal adhesive system and the
      reactivity of the treated dentinal surface. The structure of the collagen in the
      demineralized dentinal layer also seems to influence the behavior of the bond.
      Adhesive systems that do not completely denature the fibrous collagen and leave
      interwoven banded collagen in the demineralized layer produce superior bond
      strengths (greater than 20 MPa). Other research efforts seek to develop a
      nonshrinking high-performance polymer for use as a matrix material for dental
      composite resins. Spiroorthocarbonates that expand during polymerization have
      been developed. In combination with a three-component epoxy comonomer, matrix
      resins have been produced that expand during polymerization and whose mechanical
      properties, water sorption, solubility, and degree of polymerization are
      acceptable for dental use. Further developments of nonshrinking composite resins
      and improved dentinal adhesives will greatly increase the longevity of 21st
      century composite resin restorations and should significantly ease clinical
      placement.

PMID- 8272502
TI  - Composite resins in the 21st century.
AB  - Human enamel and dentin should be used as the physiologic standards with which to
      compare composite resins, especially in the posterior region. The intrinsic
      surface roughness of composite resins must be equal to or lower than the surface
      roughness of human enamel on enamel-to-enamel occlusal contact areas (Ra = 0.64
      microns). Roughness determines the biologic strength of composite resins. The
      nanoindentation hardness value of the filler particles (2.91 to 8.84 GPa) must
      not be higher than that of the hydroxyapatite crystals of human enamel (3.39
      GPa). Composite resins intended for posterior use should have a Young's modulus
      at least equal to, and preferably higher than, that of dentin (18.500 MPa). The
      compressive strength of enamel (384 MPa) and dentin (297 MPa) and the fracture
      strength of a natural tooth (molar = 305 MPa; premolar = 248 MPa) offer excellent
      mechanical standards to select the optimal strength for posterior composite
      resins. The in vivo occlusal contact area wear rate of composite resins must be
      comparable to the attritional enamel wear rate (about 39 microns/y) in molars.
      Differential wear between enamel and composite resin on the same tooth is a new
      criterion for visualizing and quantifying the wear resistance of composite resins
      in a biologic way. Posterior resins must have a radiographic opacity that is
      slightly in excess of that of human enamel (198% Al). Based on these standard
      criteria, it can be concluded that in the 21st century the ultrafine compact
      filled composite resins may be the materials of choice for restoring posterior
      cavities.

PMID- 8272503
TI  - Clinical behavior of 21st-century adhesives and composites.
AB  - The clinical behavior of future adhesives and composite materials for dental
      restorations will be significantly improved from the performance of today's
      restorative materials. The adhesives and composites available to the practicing
      dentists in 10 years will be designed and developed as preventive resin
      restorations. They will consist largely of adhesive-sealant and composite resin
      combinations. The new restoratives will be developed in response to early
      detection of caries, resulting in smaller lesions, and smaller restored surfaces
      exposed to the oral cavity. There will be less margin length, less vulnerability
      to wear, and less microleakage. The materials of the 21st century will be less
      technique sensitive in the hands of the clinician and therefore will result in
      fewer clinical failures. The advent of better wetting and better bonding
      adhesives to both enamel and dentin, combined with nonshrinking dental resins
      that are durable, esthetic, and biocompatible, will significantly improve
      available dental health care. The clinical behavior of these 21st-century
      materials should provide longer wearing, nonleaking, esthetic restorations that
      are easily manipulated and placed by clinicians at an economical cost to dental
      patients.

PMID- 8272504
TI  - Efficacy of foam liner in 10% carbamide peroxide bleaching technique.
AB  - The purpose of this study was to determine if the use of a foam liner in a tray
      during the nightguard vital bleaching technique would cause a difference in the
      rate of bleaching or the final shade of the bleached teeth. Ten subjects were
      selected who had previously successfully bleached their maxillary arch by using a
      10% carbamide peroxide solution. Vacuum-formed guards were fabricated for the
      mandibular arch so that one quadrant was covered with a conventional-style guard,
      and the other quadrant was covered with a foam-lined guard. All patients were
      successful in bleaching their mandibular arch. No patient reported any difference
      between the two quadrants in the rate of bleaching or in the final shade, nor was
      any difference apparent to the operators clinically or in photographic
      evaluation. It appears that the addition of a foam insert does not noticeably
      alter the clinical result of home bleaching. If bleaching is successful in one
      arch, it can be expected to be effective in the other arch.

PMID- 8272505
TI  - Tooth discoloration and resolution following a luxation injury: significance of
      blood pigment in dentin to laser Doppler flowmetry readings.
AB  - Discoloration of teeth is common sequel of dental trauma and is often taken as a
      sign of irreversible pulpal degeneration, particularly if the crown becomes gray
      or blue-gray in appearance. If a viable blood supply remains or revascularization
      occurs following trauma to teeth, removal of blood pigments by normal biologic
      processes can occur. The assessment of blood flow with laser Doppler flowmetry is
      an additional diagnostic aid following dental injuries. This technology has been
      used to monitor the clinical progress of two central incisors that had been
      palatally luxated in a sporting accident. Color changes were observed and were
      correlated with symptomatic and radiographic evaluation, sensibility tests, and
      laser Doppler readings. The results of these examinations indicated that the
      blood pigment within a discolored tooth crown interfered with laser light
      transmission. The limitation of this new technology in the assessment of teeth
      discolored following trauma is significant. Visual radiographic and symptomatic
      assessment remain as the principal diagnostic criteria at the present time.

PMID- 8272506
TI  - Transgenic animals as tools for investigating hepatocyte gene regulation and
      liver disease.
AB  - Transgenic technology has been extensively used for studying regulation of
      expression of genes in the liver and for creating mouse models of liver diseases.
      The number and diversity of these studies is consistent with the myriad functions
      of the liver itself. Genes expressed in liver have been used to generate a
      variety of models for genetic engineering, with further promise for the future.
      Because of its size, diversity and extent of gene expression, and function as
      both an endocrine and exocrine tissue, the liver remains a focus of attention for
      transgenic experiments. Thus, although this tissue has already played a major
      role in the development and refinement of transgenic technology, it almost
      certainly will continue to be a tissue of major interest for gene transfer
      experiments. Because the liver is also a convenient target for somatic gene
      therapy vectors, transgenic mice will probably play an increasingly important
      role as tools for screening candidate vectors for somatic gene therapy, both for
      the efficiency of expression of the vectors and for the physiological
      consequences of such expression.

PMID- 8272507
TI  - Mechanisms of growth regulation in liver regeneration and hepatic carcinogenesis.

PMID- 8272508
TI  - Liver disease associated with alpha 1-antitrypsin deficiency.

PMID- 8272509
TI  - The epidemiology and prophylaxis of hepatitis B in sub-Saharan Africa.

PMID- 8272510
TI  - Hepatitis B control: lessons from the International Task Force on Hepatitis B
      Immunization and the Lombok Hepatitis B Model Immunization Project.

PMID- 8272511
TI  - Hepatitis E virus (HEV): molecular biology and emerging epidemiology.
AB  - The etiologic agent of what was formerly known as enterically transmitted non-A,
      non-B hepatitis has been identified as a previously unrecognized 27 to 34 nm
      nonenveloped virus designated as HEV. The full-length sequencing of four
      geographic isolates has demonstrated HEV to be a positive-sense, polyadenylated
      RNA virus expressed in three different ORFs. The identification and localization
      of (1) sequence motifs characteristic of viral nonstructural genes, (2) signal
      peptides and basic sequences characteristic of structural (capsid) genes, and (3)
      immunodominant antigens has established that the genomic organization and
      expression strategy of HEV is unlike that of other characterized positive-sense
      RNA viruses.

PMID- 8272512
TI  - Hepatitis C virus infection and organ transplantation.
AB  - HCV infection is a common cause of liver disease in both patients undergoing
      organ transplantation and the post-transplant period. Increasingly sensitive and
      specific techniques to diagnose this infection have enabled us to understand the
      relationship between pretransplant and post-transplant infection and to study the
      consequences of infection in these immunocompromised patients. The use of anti
      HCV-positive organ donors is highly controversial and will remain so until the
      natural history of post-transplant HCV infection is known. Study of the
      relationship between histological damage and level of HCV replication will likely
      provide insights into the biology of this virus and mechanisms of hepatic damage.

PMID- 8272513
TI  - Pharmacological control of portal hypertension.
AB  - The initiation and maintenance of portal hypertension, development of
      portosystemic shunts, including esophagogastric varices, and precipitation of
      variceal hemorrhage result from a number of different although related
      hemodynamic variables. Knowledge of these pathophysiological mechanisms is
      essential for an understanding of the pharmacological therapy of portal
      hypertension. Conversely, pharmacological studies continue to provide new
      insights and expand our understanding of these pathophysiological mechanisms.
      Future pharmacological studies should contribute to our understanding of the role
      of endothelial-dependent and -independent mechanisms in the regulation of
      vascular tone in chronic liver disease, the regulation of intrahepatic
      resistance, and the development and modulation of the portocollateral vascular
      bed. Ideally, this will yield increasingly effective pharmacological therapies
      for the management of portal hypertension.

PMID- 8272514
TI  - Tumor site-directed therapy for hepatocellular carcinoma using monoclonal
      antibodies against hepatoma-associated antigens.

PMID- 8272515
TI  - Surgery of hepatic tumors.

PMID- 8272516
TI  - Hepatocyte tight junctions in health and disease.

PMID- 8272517
TI  - Mechanisms and functional role of intracellular pH regulation in hepatocytes.
AB  - Intracellular pH influences and is influenced by a diverse array of
      hepatocellular processes. It is regulated by the concerted action of three plasma
      membrane H+/HCO3- transporters that serve to buffer against both acidic (Na+/H+
      exchange, Na+/HCO3- cotransport) and basic (Cl-/HCO3- exchange) metabolic
      challenges. The responsiveness of hepatocytes to these challenges is augmented by
      a regulatory interplay between pH-mediated changes in Vm and electrogenic
      Na+/HCO3- cotransport to maintain pHi and Vm within a range optimized to serve
      liver function. The cost is expenditure of metabolic energy to sustain increased
      activity of the Na+/K+ pump. The benefit is a dynamic servomechanism well-suited
      to the metabolic demands of hepatocytes, which may be found in future studies to
      be employed in other metabolically active epithelia as well.

PMID- 8272518
TI  - Hypoxia and reperfusion injury to liver.

PMID- 8272519
TI  - [Psychoanalysis--a procedure or a process?].
AB  - The author discusses two schools of thought on psychoanalysis, one regarding it
      as a scientific procedure requiring correct application, the other as a process
      initiated by the patient in an unconscious quest for what he/she is in need of.
      With reference to a case history, Casement illustrates how the analyst can be
      drawn by the patient into the experience of not being able to understand what the
      latter is trying to tell him. In the case in point, this inability to understand
      corresponds to an experience undergone by the patient in infancy when due to
      undiagnosed severe myopia he was forced to live in a state of near-blindness. In
      analysis he attempted via projective identification to give expression to the
      traumatic experience of not being able to see and understand.

PMID- 8272520
TI  - [Asymmetry and mutuality in the analytic relationship: lessons for today from the
      relationship between Freud and Ferenczi].
AB  - Against the background of the controversy between Freud and Ferenczi on the
      nature of the psychoanalytic relationship, Hoffer examines the perennial issue of
      the way in which analysts come to terms with the warring claims of asymmetry
      (Freud) and mutuality (Ferenczi) in analysis. While discerning an inherent
      tendency towards mutuality in the psychoanalytic constellation, the author
      nevertheless calls for the upholding of asymmetry because the psychoanalytic
      relationship is not a relationship "of the usual kind". The analyst, he contends,
      must sustain the tension between mutuality and asymmetry and use this reflected
      tension as a therapeutic instrument for fathoming the patient's psychic reality.

PMID- 8272521
TI  - [Postpartum depression and the illusion of symbiosis].
AB  - Post-partum depression is an important clinical phenomenon that has been
      neglected in psychoanalytic research. The author's approach to the problem
      proceeds on the basis of the postulation of a cross-generational constellation, a
      specific, pathological relation between the mother and the daughter who has
      herself become a mother. This relation is termed the "illusion of symbiosis". The
      central factor here is the mother's fantasy that her baby can fulfill for her all
      the desires that she herself was denied in childhood by her own mother. In order
      to sustain this illusion of symbiosis, frustration and anger are split off and
      frequently projected onto the father, who thus becomes the object of those
      hostile fantasies. To elucidate this constellation, Halberstadt-Freud draws upon
      a highly suggestive and impressive case history.

PMID- 8272522
TI  - ["The three of us must hold together". Psychoanalytic considerations of
      experiences of heart-lung transplantation. A hermeneutic text reconstruction].
AB  - Progress in the pharmacological control of transplant rejection must not blind us
      to the fact that the psychic integration of an implanted organ makes very great
      demands on the psychological capacity of the person involved. The authors
      describe the case of a female patient who had to undergo a combined heart-lung
      transplant as a result of an innate cardiac defect. Months after the successful
      operation she developed a set of symptoms--coughing, night-time anxiety, feelings
      of suffocation--that were not susceptible of explanation in terms of organic
      medicine. The secondary symptoms of conversion neurosis demonstrate how difficult
      the patient found it to accept the implanted organ, experienced as both exciting
      and repellent, as part of her own body.

PMID- 8272523
TI  - [A factor counteracting psychological change: no resonance].

PMID- 8272524
TI  - Emergent simple discrimination in children: preference for non-preferred stimuli.
AB  - Previous research (Smeets, 1991) suggested that when given a new discrimination,
      children respond on the basis of physical similarity with previously
      discriminated stimuli. They respond to a stimulus similar to another preferred
      stimulus (S+ transfer) and respond away from a stimulus similar to another
      nonpreferred stimulus (S- transfer). When both types of transfer apply to the
      same stimulus (S+ transfer prevails, S+ Priority Transfer (S+PT). The present
      study demonstrated that S+PT also occurs when the criterion task consists of two
      nonpreferred stimuli. When given a choice between two previously nonpreferred
      stimuli, one similar and one dissimilar to other preferred stimuli, children
      select the first one. They do not so, however, when a nonpreferred stimulus
      resembling another preferred stimulus is presented with a new nonpreferred
      stimulus. These findings suggest that the children's preferences were not based
      on the physical resemblance with other (non)preferred stimuli but on the
      functions (S+, S-, S0) of individual stimulus components. A theoretical model is
      presented that accounts for all experimental data reported in the previous and
      present study. The model implies that discriminative responding not only results
      from but also determines the functional properties of individual stimulus
      elements.

PMID- 8272525
TI  - Emergent conditional discrimination in children: matching to compound stimuli.
AB  - This study reports two experiments that first taught preschool children identity
      matching to compound sample and compound comparison stimuli. A compound stimulus
      consisted of a colour and a form superimposed on one another. Test sessions
      assessed whether children related the form and colour elements of a particular
      compound stimulus. The test for this was matching to sample in which an arbitrary
      conditional discrimination was required. A majority of the children selected the
      correct colour comparison in the presence of each form sample. The children also
      showed the reverse sample-comparison relations: they matched form comparisons to
      the corresponding colour samples, respectively. In the context of these arbitrary
      relations, new colours were paired with the form elements of the samples
      (Experiment 1), and new form elements were paired with the colour elements of the
      comparisons (Experiment 2). Subsequent tests assessed whether the new stimulus
      elements had control over responding when presented as single samples or
      comparisons. Test results showed that most subjects were able to relate the new
      stimulus elements to the corresponding colour and form elements, respectively.
      The study demonstrated that matching to compound stimuli in training and testing
      conditions may generate conditional relations between the individual stimulus
      elements.

PMID- 8272526
TI  - Differences in performance of young and old monkeys on a visuospatial memory
      task.
AB  - Two groups of stumptailed macaques (Macaca arctoides) were compared in terms of
      performance on a visuospatial working memory task involving repeated
      presentations of an array of 15 doors, each of which concealed one food reward at
      the start of a session. Rewards obtained by the subject were not replaced. Errors
      were defined as responses to doors previously pushed open during the session.
      Both groups generally obtained all rewards and showed improved performance across
      sessions, but old monkeys consistently made more errors than young ones,
      especially in the latter half of a given session. Further, old monkeys were less
      diverse in the errors they made, indicating different response strategies by the
      two groups.

PMID- 8272527
TI  - Effects of ageing on visual discrimination learning in Drosophila melanogaster.
AB  - Two experiments examined conditioned suppression of the Proboscis Extension
      Response (PER), unconditionally released by sucrose stimulation of gustatory
      tarsal receptors, in young (7-day-old), middle-aged (30-day-old) and old (50-day
      old) Drosophila melanogaster males, reared at 25 degrees C. Individual flies were
      trained in a differential conditioning procedure in which a white stimulus
      signalled a quinine reinforcer, whereas a black stimulus was non-reinforced. When
      trained from the outset with the discriminative procedure, flies of all ages
      acquired the discrimination, although the acquisition of PER suppression to the
      white stimulus was retarded in middle-aged and old flies. The retardation of the
      acquisition of PER suppression in middle-aged and old flies was replicated in a
      second study in which the files received simple conditioning to the white
      stimulus prior to discrimination training.

PMID- 8272528
TI  - Capacity of goat epididymal spermatozoa to undergo the acrosome reaction and
      subsequent fusion with the egg plasma membrane.
AB  - The capacity to undergo the acrosome reaction and subsequent fusion with the egg
      plasma membrane was examined in goat epididymal spermatozoa. Spermatozoa from the
      proximal and distal caput and distal cauda were preincubated in a sealed glass
      tube for induction of the acrosome reaction, and their viability, acrosome
      morphology and penetrability into zona-free hamster eggs were determined. A
      simplified triple-stain technique revealed that most of the preincubated live
      spermatozoa in the samples from the distal caput and distal cauda epididymides
      underwent morphological changes that indicated the occurrence of the acrosome
      reaction. Electron microscopic examination revealed that the outer acrosomal
      membrane of many spermatozoa in these samples showed fusion at multiple sites to
      the plasma membrane. However, the rates of acrosome-reacted cells in the proximal
      caput spermatozoa were still lower. The sperm penetration assay demonstrated that
      the penetration rates of distal caput and distal cauda spermatozoa preincubated
      for 2 h were 93% and 74% respectively, whereas proximal caput spermatozoa
      scarcely penetrated into eggs. These results indicate that increasing numbers of
      goat spermatozoa improve in the functions related to the acrosome reaction and
      subsequent fusion with the egg plasma membrane during their transit through the
      caput epididymidis.

PMID- 8272529
TI  - Changes in oestrogen receptor protein, mRNA expression and localization in the
      endometrium of cyclic and pregnant gilts.
AB  - Conceptus secretion of oestrogen on Day 11 of gestation is involved with
      establishment of pregnancy in the pig. Changes in oestrogen receptor (ER)
      protein, mRNA and cellular localization in the endometrium were evaluated during
      the oestrous cycle and early pregnancy of the gilt. In nonpregnant gilts,
      concentration of nuclear ER in the endometrium increased from Days 0 to 12
      followed by a decline on Day 15 of the oestrous cycle. In pregnant gilts, changes
      in endometrial nuclear ER during Days 10, 12, 15 and 18 were similar to that in
      cyclic pigs. Analysis of endometrial ER mRNA expression did not detect any
      difference between cyclic and pregnant pigs between Days 10 and 15 postoestrus.
      Expression of ER mRNA in endometrium of cyclic and pregnant gilts was greatest on
      Day 10 followed by a decline on Day 15. Endometrial ER mRNA increased on Day 18
      of the oestrous cycle, but remained low during pregnancy. Immunocytochemical
      localization of ER in the endometria of cyclic and pregnant gilts indicated that
      there was intense staining for ER in stromal cells and moderate to strong
      staining in surface and glandular epithelial cells during oestrus (Day 0) and Day
      18 of the oestrous cycle. However, stromal ER staining was absent from Days 5 to
      15 of the oestrous cycle and continued to be suppressed on Day 18 of pregnancy.
      Immunocytochemical staining of ER in the surface and glandular epithelium was
      readily detectable from Days 0 to 12 of the oestrous cycle and during pregnancy.
      Intensity of staining for ER declined in surface epithelial cells on Day 15 in
      both cyclic and pregnant pigs whereas positive staining for ER in glandular
      epithelium was absent. Staining for ER on uterine surface epithelial cells
      increased during pro-estrus (Day 18) of cyclic gilts but remained similar to Day
      15 in pregnant gilts. Changes in endometrial ER protein, mRNA and localization in
      surface epithelium are consistent with a physiological role for conceptus
      oestrogen secretion in uterine function and maternal recognition of pregnancy in
      the pig.

PMID- 8272530
TI  - Reproductive cycles and pregnancy in interspecific sheep<==>goat chimaeras.
AB  - The objectives of the current study were to determine whether interspecific
      sheep<==>goat chimaeras exhibited reproductive cycles of their component species
      and were capable of maintaining ovine and caprine pregnancies to term. All
      chimaeras had oestrous cycles and several exhibited characteristics of both ewes
      and does, including short, 6-7-day cycles. Sixteen caprine pregnancies were
      confirmed in eight sheep<==>goat and one hybrid<==>sheep chimaera from 21 embryo
      transfers; of these, six appeared normal by ultrasonographic examination during
      Weeks 5 or 6, but none progressed beyond Week 8. Three apparent pseudopregnancies
      developed in two animals. In contrast, eight of 11 pregnancies in chimaeras
      resulted in term ovine offspring after transfer of ovine embryos or natural
      matings with rams. By comparison, interspecific (caprine or hybrid) pregnancies
      in ewes were lost in Week 4 (n = 8) or Weeks 5-6 (n = 2). First interspecific
      (ovine or hybrid) pregnancies in does were maintained longer (Weeks 6-12, n = 7)
      than second interspecific pregnancies (Weeks 4-5, n = 5) (P < 0.05) or
      interspecific pregnancies in ewes (P < 0.05). The results suggest that abnormal
      fetomaternal interactions during the early stages of implantation are responsible
      for termination of caprine pregnancies in the ovine or chimaeric uterus, whereas
      ovine conceptuses are able to implant successfully in the chimaeric uterus. All
      chimaeras were fertile, since each carried at least one ovine pregnancy to term
      following natural matings with rams.

PMID- 8272531
TI  - Platelet activating factor (PAF) enhances mitosis in preimplantation mouse
      embryos.
AB  - Preimplantation mouse embryos were used to determine whether the reported
      significant increase in embryo metabolism and viability achieved through
      supplementation of the culture medium with the ether phospholipid 1-o-alkyl-2
      acetyl-sn-glycero-3-phosphocoline (platelet activating factor, PAF) is
      attributable to an enhanced rate of mitosis. Blastocyst-stage embryos cultured in
      the presence of 0.186 to 18.6 microM exogenous PAF had a significantly (P < 0.01)
      higher mitotic index (the proportion of cells arrested in metaphase following
      incubation in colchicine) than those cultured without PAF. At the 8-cell stage,
      29% more blastomeres were in metaphase in the PAF-treated group (P < 0.01) 8 h
      after the addition of colchicine, but by 16 h there was no difference between
      groups; thus, PAF increased the rate at which cells entered metaphase but did not
      increase the total number. The mitotic index showed a negative correlation with
      the number of cells within blastocysts. PAF had a significantly (P < 0.01)
      greater impact on the mitotic index of blastocysts with fewer cells. The action
      of PAF was specific, being completely blocked by the PAF-receptor antagonist WEB
      2086 (33 microM). In the absence of exogenous PAF the mitotic index was lower
      with WEB 2086 than without, suggesting inhibition of the action of endogenous
      embryo-derived PAF. These results show that PAF stimulates the rates at which
      cells within the preimplantation mouse embryo enter metaphase in vitro and
      suggest that it would decrease their doubling time, perhaps accounting for the
      embryotrophic actions of PAF.

PMID- 8272532
TI  - Prostaglandin production by the oocyte cumulus complex around the time of
      fertilization and the effect of prostaglandin E on the development of the early
      bovine embryo.
AB  - The oocyte-cumulus complex (25 oocytes per 250 microL medium) produced
      prostaglandin-F2 alpha (PGF2 alpha) and PGE2 during maturation, immediately
      following fertilization and for at least 48 h after fertilization. The data
      suggest that PG production is important in the development of the oocyte;
      addition of PGE2 (5 ng mL-1) to the fertilization medium increased the rate of
      cleavage and groups of oocytes with low cleavage rates produced far less PG than
      groups with high cleavage rates. Measurement of PG in the maturation medium could
      therefore be a means of assessing the suitability of oocytes for fertilization.

PMID- 8272533
TI  - Successful fertility experiments with cryopreserved spermatozoa of barramundi,
      Lates calcarifer (Bloch), using dimethylsulfoxide and glycerol as
      cryoprotectants.
AB  - The fertility of cryopreserved Lates calcarifer sperm was studied to increase the
      availability of semen for routine fertilization of stripped eggs and to provide a
      tool for selective breeding. Semen diluted (1:4 v/v) and frozen (-196 degrees C)
      with 5% dimethylsulfoxide (DMSO) or 10% glycerol (final concentration) as
      cryoprotectants was used to inseminate freshly stripped ova. Frozen-thawed sperm
      were motile for about 4 min after being mixed with seawater. In the DMSO medium,
      post-thaw sperm activation was immediate after dilution with seawater, but in the
      glycerol medium maximum motility intensity was delayed for up to 1 min. When eggs
      and sperm were mixed before the addition of seawater, semen frozen with DMSO as
      cryoprotectant gave a mean hatch rate (84.1%) no different (P > 0.05) from that
      of unfrozen semen diluted with Ringer's solution (80.7%) or with DMSO (83.7%),
      but higher (P < 0.05) than that of semen frozen with glycerol (60.9%). Adding
      sperm to seawater 30 s before mixing with eggs did not improve the fertility of
      sperm cryopreserved with glycerol. Eggs inseminated with glycerol-cryoprotected
      sperm showed higher mortality during incubation than those inseminated with DMSO
      cryoprotected sperm. Sperm held in liquid nitrogen for 90 days with DMSO as
      cryoprotectant yielded acceptable fertilization and hatching rates with semen-to
      ova ratios of up to 1:100 (v/v) , and produced fish with no apparent
      abnormalities over a 29-day period after hatch. These results show that
      cryopreservation of L. calcarifer sperm is feasible and well suited to a variety
      of hatchery purposes.

PMID- 8272534
TI  - Acute effects of ethane dimethane sulfonate (EDS) on the structure of the cauda
      epididymidis in the rat: selective destruction of clear cells in the proximal
      cauda region.
AB  - Of eight groups of five adult male Sprague-Dawley rats, three groups received an
      intraperitoneal dose of EDS (75 mg kg-1) in DMSO (dimethylsulfoxide in water;
      1:3) and three control groups received DMSO only. One EDS and one control group
      were killed 1, 2 and 3 days after treatment. One EDS+T group, given a 5-cm
      implant of T sufficient to maintain normal serum T concentrations, and one
      untreated control group were killed on Day 3. Epididymides were fixed by vascular
      perfusion and embedded in Epon/Araldite for light and electron microscopic
      studies. Epididymal duct diameters and epithelial heights were measured from 1
      micron sections and structural changes were assessed from thin sections using a
      Jeol 100B electron microscope. Morphological studies showed a reduction in duct
      diameter and an associated increase in epithelial height in the proximal cauda
      epididymidis of the experimental groups. In the EDS+T implant group, epithelial
      heights were significantly greater than in controls but duct diameters remained
      unchanged. The most obvious structural change in the proximal cauda epididymidis
      was the selective destruction of clear cells in the epithelium. Initially,
      vacuoles were observed in the lateral intercellular spaces of the epithelium;
      large autophagic vacuoles then appeared in the clear cells, which had degenerated
      and disappeared from the epithelium by Day 3. Progressive infiltration of
      leucocytes into the intertubular interstitium, the epithelium and lumen of the
      proximal cauda was also observed. Loss of clear cells in the proximal cauda
      epididymidis was also seen in the EDS+T group, suggesting that clear-cell
      degeneration was not associated with reduced concentrations of circulating
      androgen. In all EDS-treated groups, however, clear cells and duct profiles in
      the distal cauda epididymidis remained unaffected. The reason for their
      protection from the effects of EDS has not yet been determined. These results
      suggest that, in addition to other specific lesions described in previous
      studies, EDS also has a direct effect on the rat epididymis that appears to be
      specifically targeted to the clear cells in the proximal caudal region.

PMID- 8272535
TI  - Fertilizing capacity of bovine spermatozoa selected after swim-up in hyaluronic
      acid-containing medium.
AB  - Hyaluronic acid (HA) was used to select spermatozoa from frozen-thawed semen from
      five bulls; two were highly fertile and three had low fertility related to low
      post-thaw motility of the spermatozoa. Spermatozoa were collected after 1 h of
      self-migration in one of two media: a modified Tyrode's lactate solution (TALP)
      or a medium consisting of equal volumes of TALP and phosphate-buffered saline to
      which HA was added to obtain a final concentration of 1 mg mL-1 (HA medium). The
      selected spermatozoa were used to inseminate oocytes matured in vitro at a
      concentration of either 1.0 x 10(6) or 0.5 x 10(6) mL-1, constituting a 5 x 2 x 2
      factorial experiment. After 19-22 h of sperm-oocyte co-incubation, fertilization
      of oocytes was assessed. The two concentrations of spermatozoa differed
      significantly in the percentage of oocytes penetrated (P = 0.001) and the
      percentage of oocytes with two pronuclei (P = 0.002). When 1.0 x 10(6) mL-1
      spermatozoa were used, spermatozoa collected after swim-up in the HA medium
      fertilized more oocytes (P = 0.01) than did those collected after swim-up in
      TALP. Variation between bulls was also significant (P = 0.002). The beneficial
      effect of the HA medium was more evident in the group of low-fertility bulls (P <
      or = 0.03), where neither the variation between bulls (P > or = 0.06) nor the
      interaction between the methods of sperm selection and bulls (P > or = 0.10) was
      significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272536
TI  - Effect of oxygen concentration on the incorporation of glucose by the sheep
      conceptus between days 13 and 19 of pregnancy.
AB  - Embryos and extraembryonic membranes recovered from the sheep conceptus on Days
      13, 15, 17 and 19 of pregnancy were incubated in medium containing glucose as
      sole energy substrate. In all components of the conceptus 60-70% of substrate
      carbon incorporated was recovered in the non-glycogen acid-soluble fraction, 25
      30% in non-glycogen macromolecules and 4-8% in the glycogen pools. At all stages
      of development examined, embryonic tissue accumulated more glucose carbon into
      all fractions than did yolk sac which in turn was more active than trophoblast.
      After its appearance, the allantois was at least as active in glucose
      incorporation as embryonic tissue. Over the period of development examined,
      incorporation into all tissues of the conceptus fell progressively as pregnancy
      advanced and, by Day 19, total incorporation was about 60% of the initial value
      for each component. Reduction in oxygen concentration generally depressed
      incorporation into all intracellular carbon pools. The most consistent and
      significant effects were recorded for the two non-glycogen pools where
      incorporation fell, on average, by 30-40% when O2 concentration was reduced to
      1%. Most of the response observed was due to a drop in O2 concentration from 20
      to 5% with smaller additional effects when the O2 was further reduced to 1%.
      Incorporation into all pools isolated tended to follow a similar pattern and
      incorporation into the three macromolecular components, expressed as a percentage
      of total incorporation, remained unchanged as O2 concentration was reduced.

PMID- 8272537
TI  - Contribution of the pentose phosphate pathway to glucose utilization by
      preimplantation sheep embryos.
AB  - The activity of the pentose phosphate pathway of glucose metabolism in early
      sheep embryos and in the structures of the advanced conceptus from Day 13 to Day
      19 of pregnancy was measured quantitatively during a 2.5-h incubation with
      glucose as sole energy source. For embryos during cleavage, activity of this
      pathway accounted for 6-9% of total glucose utilized. The proportion of glucose
      metabolized through the pentose pathway fell progressively with development and
      by Day 19 represented 1-2% of glucose turnover. However, total turnover of
      glucose increased eight fold between the 2-cell and blastocyst stage and the
      amount of glucose processed through the pentose pathway increased over this time
      despite the fall in the proportion utilized in this way. In contrast, glucose
      turnover by the advanced embryo and its extra embryonic membranes progressively
      decreased as the structures developed. As a result, estimates of the amount of
      glucose utilized through the pathway per microgram dried weight per hour declined
      to low values at Day 19 following the peak in activity at about the time of
      blastulation. Trophoblast and yolk sac processed less glucose through the pentose
      pathway per microgram dried weight than embryonic tissue but the allantois was
      similar to the embryo. Overall, the pentose pathway accounted for a relatively
      constant proportion of the CO2 produced from glucose under these experimental
      conditions with values generally between 15 and 20% of total CO2 produced. When
      activities in the components of the advanced conceptus were expressed as the
      total amount of glucose processed through the pathway per hour, turnover in the
      embryo, allantois and yolk sac increased progressively with time. By contrast,
      there was a substantial trough in the activity of the trophoblast on Day 17 of
      pregnancy.

PMID- 8272538
TI  - Congenital absence of vas deferens treated by artificial spermatocele constructed
      from the tunica vaginalis; report of six cases.
AB  - Six patients with congenital absence of the vas deferens were treated by
      artificial spermatoceles (ASCs) in an attempt to collect sperm for subsequent
      artificial insemination (AI). The ASC was constructed from a flap of tunica
      vaginalis from the patient. Sperm were aspirated from the ASC each month; there
      was wide variation in the concentration of sperm recovered [33.0 +/- 48.2 x 10(6)
      mL-1 (range 0.1-200)] and motility and normal morphology of the sperm were 19.0
      +/- 17.9% and 48.8 +/- 23.4% respectively. Although a total of 14 cycles of AI
      was performed using the aspirated sperm, pregnancy did not result. Both poor
      sperm recovery and poor motility contributed to this failure. The condition of
      the epididymis observed during scrotum examination is reported. It is suggested
      that in some patients with congenital absence of vas deferens, the paired
      Wolffian ducts may differ from each other in their development.

PMID- 8272539
TI  - [Bioethics and radiology. A possible method between necessity and imagination].

PMID- 8272540
TI  - [Ultrasonographic evaluation of the sciatic nerve and thigh trauma].
AB  - This study was aimed at studying the normal morphology of the main extrapelvic
      trunk of the sciatic nerve, its average size and its anatomo-topographic
      relationships by means of high resolution US. The involvement of the sciatic
      nerve in traumas was also investigated. The lower gluteal region and the
      posterior aspect of both thighs were examined in 30 healthy subjects and in 11
      patients with recent or previous traumas. The sciatic nerve is clearly
      demonstrated, on US images, between the biceps femoris muscle and the
      semimembranosus and semitendinosus muscles. The average dorsoventral diameter of
      the nerve is 6.4 mm at the upper third and 4.8 mm at the middle third of the
      thigh, while its average transverse diameter is 11.8 mm at the middle third of
      the thigh. In traumas, US demonstrated compression and displacement of the
      sciatic nerve in 6 recent hematomas and in 2 hypertrophic ossei calli of the
      femoral diaphysis. In 2 osteomyelitis cases with a posterior thigh fistula, US
      showed sciatic nerve involvement by the phlogistic process. Moreover, US allowed
      an old thick thrombosis of a satellite vein of the sciatic nerve to be depicted.
      In conclusion, the present study has demonstrated that US not only clearly
      depicts the sciatic nerve but also provides accurate information on its
      involvement in recent or previous traumas.

PMID- 8272541
TI  - [Angiography with magnetic resonance of the ++carotid arteries. Evaluation of
      clinical results obtained with low magnetic field equipment].
AB  - Magnetic Resonance Angiography (MRA) is the latest diagnostic technique for the
      noninvasive evaluation of cardiovascular conditions. This technique has proved to
      be especially useful in the study of carotid arteries. All the clinical studies
      reported to date have been obtained at high or medium field strength; our purpose
      is to assess the clinical value of MRA in the evaluation of carotid arteries at
      low field strength. All the exams were performed with an 0.2 T permanent magnet,
      using the 2D time of flight (TOF) technique, the only one which is currently
      available on our equipment. Forty-two patients with clinical diagnosis of
      cerebrovascular insufficiency were examined. In all cases MRA findings were
      confirmed with digital subtraction angiography (DSA), which was considered the
      gold standard. The double-blind evaluation of the results showed high agreement
      of the two techniques in 70 of 84 carotid arteries. A mild tendency to
      overestimation was observed in 4 normal cases considered as mild stenoses on MRA,
      in 2 cases with mild stenosis considered as discrete stenoses on MRA and in 1
      case of severe stenosis considered as an occlusion on MRA. Underestimation was
      seen in 1 case of mild stenosis considered as normal on MRA, in 2 cases of
      discrete stenosis which appeared as mild stenoses on MRA and in 2 cases of
      occlusion considered as severe stenoses. Our study showed high agreement between
      MRA and DSA results, which means that high quality exams can be obtained even at
      low field strength. Further progress can be expected when 3D TOF and phase
      contrast techniques will be introduced.

PMID- 8272542
TI  - [Study of spondylodiscitis with magnetic resonance. Use of gadolinium-DTPA].
AB  - Eighteen patients suffering from spondylodiscitis were examined with MRI and 22
      pathologic levels were identified: 1 cervical, 6 thoracic and 15 lumbosacral. As
      for etiology, 4 cases were tubercular, 3 strepto-staphylococcal, 3 brucellar 1
      strepto-bacteroides and 11 of unknown origin. Five patients underwent MR follow
      up 4-9 months after the clinical onset. SE T1- and T2-weighed sequences were
      always performed and 11 patients, with 13 pathologic levels, also underwent SE T1
      weighted sequences with i.v. Gd-DTPA administration. No correlation could be made
      between the signal intensity of the involved vertebral bodies and disks and
      etiology. On SE T1-weighted sequences 91% of the vertebral bodies were
      hypointense, whereas the intervertebral disks were hypointense in 55% of cases
      and isointense in 45%. On SE T2-weighted sequences, the vertebrae appeared
      hyperintense in 65% of the cases while the disks were hyperintense in 55% and
      isointense in 41%. After Gd-DTPA injection signal intensity increased in 100% of
      cases, both at the body and at the disk. In 6 cases an inflammatory infiltration
      of the intracanalar structures was found, whose identifications was possible, in
      4 cases, only after contrast medium injection. In the follow-up of 5 cases at 4-9
      months the vertebral bodies remained hypointense in 3 cases on T1-weighted
      sequences, while in 2 cases signal intensity tended to normalize. Signal
      normalized in 4 cases on T2-weighted sequences. In 2 follow-up examinations disk
      structures were never depicted, neither on T1- nor on T2-weighted sequences. To
      conclude, T1-weighted sequences appear to be more sensitive than T2-weighted
      sequences to demonstrate inflammatory processes in the vertebral bodies, while
      the two sequences are equivalent to evaluate the disks. Gadolinium-enhanced T1
      weighted sequences were more sensitive than the T1- and T2-weighted ones,
      especially to assess the extent of inflammatory processes into the spinal canal
      and to evaluate their persistence. The authors suggest the use of unenhanced and
      enhanced SE T1-weighted sequences only at least in the follow-up of
      spondylodiscitis.

PMID- 8272543
TI  - [Tendinopathy of the patellar ligament secondary to transtendineal arthroscopy of
      the knee. Ultrasonographic evaluation].
AB  - During knee arthroscopy, the transtendinous approach best visualizes articular
      structures, even though it may cause patellar tendinitis, following the surgical
      procedures. Thirty patients (22 men and 8 women) who had undergone transtendinous
      arthroscopy of the knee were submitted to clinical and US follow-up at 3, 6, 12
      months. This monitoring was aimed at correlating clinical and instrumental
      findings of the above iatrogenic condition. Painful symptoms were present in 30%
      of the cases in group I, in 10% of group II and in no patient in group III. US
      demonstrated thickening of the patellar tendon in all the three groups of
      patients, with reduced echogenicity and blurred margins at the arthroscopic
      portal, plus decreasing gravity over time. The US pattern of arthroscopic
      surgical gap was observed in all patients in group I, in 10% of patients in group
      II and in none of the patients in group III. In conclusion because of its
      clinical course and of its US findings, in our experience patellar tendinopathy
      following transtendinous arthroscopy of the knee is not to be considered as a
      iatrogenic inflammatory or degenerative sequela, but as a physiological
      cicatricial evolution of the surgical transtendinous breach. The US follow-up of
      the latter allows the correct assessment of the recovering process.

PMID- 8272544
TI  - [The use of automatic devices for ultrasonography-guided histologic biopsy of
      breast lesions].
AB  - The authors report their experience with the use of biopsy guns for the
      histologic sampling of breast lesions. Cytologic sampling by means of FNAB has
      been preferred so far because it was thought to be simpler, less risky and more
      reliable. Nevertheless, cytologic sampling exhibits several drawbacks--e.g., the
      need of repeated punctures to get sufficient cell material, frequent problems in
      diagnosing benign lesions and the decisive influence of the operator's skills.
      The use of biopsy guns for histologic sampling solves the above problems, because
      the value of the sample is not affected by the operator's skills; moreover, fewer
      punctures are needed and their value does not depend on lesion nature. Our series
      of cases includes 65 patients who underwent histologic sampling for suspected
      lesions over 10 months. A hundred and seventy-two samples were collected and 77
      lesions were diagnosed, 47 of them malignant and 30 benign (fibroadenomas,
      fibrocystic changes, epitheliosis). Sensitivity, specificity and diagnostic
      accuracy of the method were 93.6%, 100% and 96.1%, respectively, with 6.4% false
      negative due to 3 cases where the lesion was not centred due to misguidance.

PMID- 8272545
TI  - [Volumetric computerized tomography (spiral CT). Technical principles and
      possible applications in the thorax].
AB  - Spiral volumetric CT is a new volume scanning technique allowing the one
      acquisition imaging of an anatomical volume, by advancing the patient through a
      continuously rotating X-ray tube. As a result, the X-ray tube moves in spirals
      around the patient and this is the reason why this new technique is called Spiral
      CT. At the end of the acquisition, planar images are reconstructed by means of a
      dedicated image reconstruction algorithm with a linear interpolation between two
      contiguous spiral segments. Spiral CT offers many advantages, all resulting from
      the possibility of evaluating anatomical volumes in a short time: the organs
      which are subject to respiratory motion can be studied in a single breath-hold
      scan, the quality of secondary reconstructions (2/3 dimensional) is improved, the
      use of contrast media is optimal and finally motion artifacts are reduced. The
      authors report their early experience with spiral CT in the chest. Spiral CT is
      more reliable than conventional CT in the evaluation of pulmonary nodules, which
      can be easily identified with no risk of missing small lesions, and of the
      pulmonary apex and of the diaphragm. Moreover, contrast media can be used at a
      lower dosage than usually recommended with conventional CT.

PMID- 8272546
TI  - [Peripheral pulmonary neoplasms: combined imaging (computerized tomography,
      ultrasonography, magnetic resonance) in the evaluation of chest wall
      involvement].
AB  - Chest wall involvement by a peripheral lung neoplasm, found in 4-8% of the cases,
      makes a difference in both staging and surgical approach. In the evaluation of
      the regional extent of the tumor, the radiologist must give the surgeon as much
      information as possible about relationships between lung neoplasm and chest wall
      structures, to correctly evaluate stage-T2 cancers and differentiate them from
      stage-T3 cancers. The authors report the results of a study made to assess the
      value of Computed Tomography (CT), ultrasonography (US) and Magnetic Resonance
      Imaging (MRI) to define chest wall invasion by a peripheral bronchogenic
      carcinoma. To this purpose 25 patients with primary peripheral lung neoplasm were
      studied with CT, US and MRI and the results were compared with surgical findings
      by means of TNM classification. Overall sensitivity and specificity were 68% and
      74% for CT, 74% and 72% for US and 88% and 86% for MRI, respectively. CT, which
      still plays the major role in staging lung cancer, seems to get the worst results
      because of its impossibility to differentiate the cancers adjoining the chest
      wall from those showing signs of initial invasion. In these cases the use of the
      other imaging techniques (US, MRI) depends on their availability and on the
      specific experience of the radiologist.

PMID- 8272547
TI  - [Evaluation of bronchiectasia with AMBER and high-resolution computerized
      tomography. Prospective study of a group of 50 patients].
AB  - The authors compared the diagnostic value of AMBER and HRCT in the evaluation of
      bronchiectasis. A series of 50 patients with conventional X-ray findings
      suggestive of this condition (increased pulmonary markings, loss of pulmonary
      volume and segmental cysts) were submitted to HRCT. In all the patients with
      bronchiectasis (25/50), AMBER showed increased pulmonary markings in one or more
      localizations, while loss of pulmonary volume was observed in 22 cases and
      segmental cysts in 8. The positive predictive value (PPV) of these findings was
      50% for increased markings, 59% for the loss of pulmonary volume, 64% for the
      association of the former two signs and finally 100% for segmental cysts. The
      false-positive cases were due to bronchial wall thickening and to areas of
      peribronchial fibrosis. On the basis of their findings, the authors conclude
      that, except for the finding of segmental cysts, AMBER does not allow the
      unquestionable diagnosis of bronchiectasis to be made due to its low PPV (64%)
      and that further studies with HRCT are therefore required.

PMID- 8272548
TI  - [Radiologic evaluation and prognosis of lymphoid nodular hyperplasia of the
      mesenteric intestine].
AB  - Nodular lymphoid hyperplasia (NLH) is a reaction of the intestinal lymphatic
      tissue to specific inflammatory stimuli. Radiologically, it presents with
      multiple nodular filling defects of various sizes (2-4 mm) and with segmental,
      focal or diffuse distribution. The condition may be benign but, under particular
      circumstances (chronic stimuli), it may evolve to neoplastic forms. Seven hundred
      and sixty-eight patients underwent small bowel X-rays from January 1990 to April
      1992. Twenty-two patients with NLH with or without associated mucosal or wall
      lesions were selected. The radiologic and histologic features of the lesions,
      together with the clinical data, were helpful to make the diagnosis. In 8
      patients the hyperplastic nodules were benign, while 10 patients were affected
      with Crohn's disease and 4 with Herman's syndrome or common variable
      immunodeficiency. This work was aimed at defining NLH from a diagnostic point of
      view relative to both morphology and extent of lesions and at stressing the role
      of radiology of the small bowel in the follow-up of the cases at risk of evolving
      to cancer.

PMID- 8272549
TI  - [Diagnosis of gastro-esophageal reflux in children. Ultrasonography versus pH
      monitoring].
AB  - The reliability of ultrasonography (US) was investigated in the diagnosis of
      gastroesophageal reflux in the pediatric patient. Therefore, specificity and
      sensitivity of US were compared with those of a 24-hour pH monitoring. A hundred
      and twenty-nine patients were examined; their age ranged 38 days to 14 years (56
      were under and 73 over 2 years old). Since these patients presented with
      gastroesophageal symptoms, they underwent both pH monitoring and US. The results
      of the two methods were in agreement in 79.8% of the cases. Notably, in the age
      group ranging 0 to 2 years, US exhibited greater sensitivity (87% vs. 78.8%) and
      slightly lower specificity (76.5% vs. 81.1%) than in the age group ranging 2 to
      14 years. The greater sensitivity in the 0-2 age group can be explained by
      physiological factors (which are typical of the first months of life) as well as
      by technical factors. Therefore, in infants, US should be combined with pH
      monitoring to identify the cases which are unquestionably pathological. The high
      specificity in the children over 2 years of age could justify the use of US alone
      in this group of patients for both diagnosis and follow-up, while pH monitoring
      might be used only in the most severe and/or complicated cases. The results
      suggest that, in the two age groups considered, abdominal US can be used not only
      as the diagnostic method of choice in the study of gastroesophageal reflux, but
      also as an extremely useful tool during follow-up when therapeutic monitoring is
      also needed.

PMID- 8272550
TI  - [Experience with the combined diagnosis and therapy of locally advanced carcinoma
      of the uterine cervix (stage FIGO IIB-III). Transrectal ultrasonography and CT in
      the staging and in follow-up after therapy. Preliminary results].
AB  - The diagnosis, staging, therapy and follow-up of advanced epidermoid cervical
      carcinoma (FIGO stages IIB-III) have been studied in our university since January
      1990. By December 1992, a team of specialists including radiologists,
      radiotherapists, gynecologists and pathologists divided 54 patients into two
      random treatment groups: group A patients, after systemic chemotherapy (CDP, 2
      cycles) and diagnostic reevaluation, underwent radical surgery; group B patients
      received conventional radiotherapy alone (ERT 45 Gy+IRT or END-RT 20-25 Gy). All
      patients were examined by means of transrectal US (TRUS) and CT, after clinical
      examination under sedation, at staging and during the follow-up. The exams were
      performed periodically for group B patients and after systemic chemotherapy for
      group A patients. Imaging findings were compared with pathology only in group A.
      All imaging results were filed. The results confirm some literature data--e.g.,
      62% diagnostic accuracy for CT and 69% for TRUS, with higher diagnostic accuracy
      of the latter to evaluate cervical volume and to diagnose local relapses. As for
      parametrial involvement, both imaging methods tend to understage the early
      involvement, but only CT tends to overstage the lesions, especially in irradiated
      patients, due to fibrosclerosis phenomena. TRUS exhibited 69% accuracy, 70%
      sensitivity and 69% specificity, versus 61%, 62% and 60%, respectively, for CT;
      clinical examination under sedation had 58%, 60% and 60%, respectively. Both TRUS
      and CT are faster than endoscopic methods in evaluating vesical and/or rectal
      involvement. Lymph node metastases at staging, especially those in lumboaortic
      locations, proved to be unfavorable prognostic signs, as demonstrated by
      lumboaortic lymph node relapses in 5 group B patients (only 2 of them presented
      with lymph node metastases at staging; 3 patients had micronodules near the renal
      vessels), in spite of good local response after radiotherapy. In conclusion, we
      would like to point out that our team has had an MR unit at its disposal only
      recently: since the method is considered as the gold standard of imaging,
      especially in this kind of lesions, the study is still in progress.

PMID- 8272551
TI  - [Ultrasonographic semiology of biliary prostheses].
AB  - US was used to study 60 patients with different types of plastic (Home-made,
      Lunderquist, Miller, Carey-Coons, Lammer) and metallic (Z-stent, Wallstent)
      biliary stents, from October 1990 to March 1993. The optimal US approach was
      assessed, together with several US features which are typical of each type of
      endoprosthesis. As far as plastic endoprostheses are concerned, independent of
      manufacturing differences, the typical US pattern on longitudinal scans is a
      hyperechoic double line while, on transverse scans, the prosthesis cylinder is
      represented by short hyperechoic lines, resembling the mathematic equal sign.
      According to the different types, metallic stents appear as thin hyperechoic
      lines or narrow gratings on longitudinal scans and as hyperechoic spots following
      a circular pattern or as a hyperechoic ring on transverse scans.

PMID- 8272552
TI  - [Percutaneous treatment of symptomatic renal cysts: effects of the combination of
      sclerotherapy with alcohol and fibrin glue (tissucol)].
AB  - The percutaneous treatment of symptomatic renal cysts has grown in therapeutic
      importance over the last years. The international literature includes many
      reports on the sclerotherapy of renal cysts with different sclerosing agents. The
      authors report their experience with the percutaneous treatment of renal cysts by
      combining pure alcohol and fibrin glue. The glue serves the purpose to seal the
      walls of the cyst already damaged by alcohol. The results of the combined
      treatment show that relief of symptoms was obtained in all patients, with no
      major or minor complications. Complete cyst ablation was obtained only in 16% of
      cases, while a partial recurrence was seen in 80% of patients, with an average
      regrowth < 35% of the initial cyst volume. None of these patients presented
      further symptoms. At present, the follow-up time ranges 3 to 34 months.

PMID- 8272553
TI  - [The hadron therapy project].
AB  - The neologism "hadrontherapy" means radiotherapy with hadrons, which are the
      particles constituted by quarks, such as protons, neutrons and ions. The
      theoretical considerations about the clinical advantages this treatment modality
      can yield and the results obtained at the centers where it has already been used
      justify the proposal to project a center of this kind also in our Country. To
      this purpose, two of the authors of this paper (U. Amaldi, G. Tosi) founded the
      TERA Group formed by physicists, engineers and radiotherapists who work in close
      collaboration on a feasibility study for a hadrontherapy facility. The first aim
      of the Hadrontherapy Project is to design a center equipped with a synchrotron
      which, at the beginning, will accelerate negative hydrogen ions (H-) which will
      first produce 70-250 MeV proton beams and, then accelerate light ions (up to 16O)
      to 430 MeV/amu. This accelerator will serve four or five treatment rooms where
      patients can be irradiated simultaneously. Two rooms will be equipped with a
      fixed horizontal beam for the treatment of eye, head and neck tumors; the others
      will be equipped with rotating gantries to administer, in any clinical situation,
      really adequate treatment. Such a unit, when enough experience is fained, will
      allow at least 1000 patients to be treated yearly. The synchrotron injector will
      be designed so as to allow, parallel to the radiotherapy activities, other
      applications of medical and biological interest such as: the production of
      radioisotopes for diagnostic use (especially positron emitters), the analysis of
      trace elements through the PIXE technique and the production of thermal and
      epithermal neutrons for boron neutron capture therapy.

PMID- 8272554
TI  - [SARO: a system for irradiating small intracranial tumors under the guidance of
      magnetic resonance imaging].
AB  - An MR-based system for the accurate irradiation of small intracranial tumors, not
      less than 5 cm in diameter, is described. The system uses a home-made device (a
      support base with millimeter scales) and a series of thin individual wood moulds.
      A full size-enlargement of the central sagittal and of the tumor-containing
      transverse MR sections is the first operative step. On these enlarged sections
      the intracranial isocentre, the entry position of the orthogonal laser beams and
      the flexion-extension degree of the patient's head are chosen. Subsequently, from
      the sagittal full-size section the fronto-naso-labial outline is cut-out and
      accurately transferred on to a thin wood plank, which is finally cut with a fine
      saw. On the plank two orthogonal lines are drawn, crossing at the target-volume
      centre and matching with both laser beams during the treatment set-up. The
      millimeter scale on the support base allows the accurate lateral displacements of
      the treatment couch, when eccentric tumors most be irradiated. By this system,
      called with the Italian acronym SARO, the patient needs neither to be shaved, nor
      to be marked on his head skin. No special shell is necessary any more. Though
      intrinsically simple, the system needs skillful accuracy during all its procedure
      steps in order to reach the desired reliability when treating small intracranial
      tumors (not less than 5 cm in diameter).

PMID- 8272555
TI  - [Exclusive radiotherapy of parotid metastases. Results in 14 cases].
AB  - Parotid metastases are uncommon lesions. In most cases the skin of the head and
      neck is the site of the primary tumor, which is usually a squamous cell carcinoma
      or a melanoma. Infraclavicular or non-cutaneous head and neck cancers one less
      likely to cause a parotid metastasis. From 1968 to 1991, 38 patients (9 men and 5
      women aged 45 to 96 years) affected with parotid metastases, were treated in the
      Department of Radiotherapy at the Ospedale Maggiore of Novara. All patients
      received exclusive irradiation. In 12 patients the primary lesion was found in
      the skin of the head and neck (11 squamous cell carcinomas and 2 melanomas), one
      had an undifferentiated nasopharyngeal carcinoma and one a squamous cell lung
      carcinoma. In 9 cases the parotid gland was the only site of metastasis, in 2
      cases lateral cervical lymph nodes metastases were also present and in 3 cases
      distant metastases. Radiotherapy was performed with cobalt 60; the target volume
      was limited to the parotid region in the N1-N2a cases and included the
      ipsilateral cervical nodes in the N2b-N3a cases. The doses ranged 24-66 Gy (mean:
      50, median-52), with daily fractionation of 1.8-2 Gy for 5 days/week. After
      radiotherapy local control was obtained in 8/14 cases (57%), maintained at 2
      years in 7/14 patients and at 5 years in 2/10 patients (20%). Eight patients
      (57%) relapsed in the parotid and/or cervical areas and/or exhibited widespread
      metastases and finally died; 6 patients (43%) were NED after a minimum 3 years'
      follow-up. Parotid metastases are usually treated by surgical resection;
      radiotherapy can be used as postoperative or exclusive treatment. Exclusive
      radiotherapy can be used for the skin cancers which are inoperable for general or
      local conditions (fixation, necrosis, ulceration), for mucosal head and neck
      cancers treated by radiotherapy and for infraclavicular tumors as a palliative
      treatment. Prognosis is different for skin cancer, mucosal and head and neck a
      carcinoma and infraclavicular neoplasms. The best results can be obtained with N1
      nodes and high-dose irradiation.

PMID- 8272556
TI  - [Physics, dosimetry, and quality control in mammography].
AB  - The diagnostic value of mammography, especially in the early diagnosis of breast
      cancer, is closely related to examination optimization in terms of high-quality
      images with the lowest possible dose to the organ. Currently, "optimal" beams are
      produced by X-ray tubes with a Molybdenum anode, their voltage reaching 35 kV,
      using the K fluorescence line at 17.48 keV and absorption of photons with > 20
      keV energy, through Mo filtration. The dose delivered with a mammographic
      examination is expressed differently in the literature reports on the subject:
      air exposure, skin exposure, dose at the midplane and mean dose; currently, it is
      recommended to specify the dose as "average glandular tissue dose", considering
      beam quality and the ratio between transmissions in perspex and tissues
      respectively. Threshold values for the average dose to the glandular tissue range
      1.8 to 3 mGy with a grid and 0.9 to 1.5 mGy without the grid. The high quality
      standard of mammography requires quality assurance programs including the
      mammographic unit and the image acquisition and treatment systems. In Italy the
      "Dose and Quality in Mammography" program is in progress. According to the
      acceptance quality criteria established in the program and on the basis of the
      investigation of 272 centers, an acceptable dose-quality ratio was seen in 37.5%
      of the centers, low quality was found in 24.5%, high dose in 23.7% and high dose
      plus low quality in 14.1% of the whole of centers.

PMID- 8272557
TI  - [Clinical usefulness of medico-nuclear methods in the study of infective
      diseases].

PMID- 8272558
TI  - [Stereotactic angiography in the localization of cerebrovascular lesions].

PMID- 8272559
TI  - [Unusual case of congenital pseudoarthrosis of the clavicle associated with
      cleidosternocostal hyperostosis].

PMID- 8272560
TI  - [Magnetic resonance imaging of the bone marrow in aplastic anemia. Description of
      a case].

PMID- 8272561
TI  - [Chemotherapy through the subclavian artery: axillary metastasis of laryngeal
      carcinoma. Description of a case].

PMID- 8272562
TI  - [Diagnosis with magnetic resonance of lipomatous infiltration of the interatrial
      septum of the heart. A case].

PMID- 8272563
TI  - [Contribution of ultrasonography, computerized tomography, and magnetic
      resonance, in the Budd-Chiari syndrome. Report of 4 cases].

PMID- 8272564
TI  - [A case of hypertrophic stenosis of the pylorus with clinico-sonographic
      inconsistency].

PMID- 8272565
TI  - [Hematoma of the abdominal wall during calciparin therapy: ultrasonography and
      computerized tomography findings. Description of 4 cases].

PMID- 8272566
TI  - [Ultrasonographic diagnosis of duplicated gallbladder in a child. Description of
      a case].

PMID- 8272567
TI  - [2 unusual complications secondary to the percutaneous treatment of renal cysts].

PMID- 8272568
TI  - [Pietro Cignolini (1897-1993)].

PMID- 8272569
TI  - Postnatal development and sex-related difference of metyrapone reductase
      activities in liver microsomes and cytosol of the rat.
AB  - A significant difference was observed between developmental patterns of
      metyrapone reductase activities in liver microsomes of male and female rats. The
      activity in liver microsomes of male rats was maintained at high levels until ten
      weeks of age after birth. In contrast, the activity in liver microsomes of female
      rats was markedly decreased until six weeks of age and reached low levels after
      eight weeks of age. As with the results of such different patterns, there were
      pronounced sex-related differences during adult period. Castration significantly
      decreased the activity in liver microsomes of male rats. This finding suggests
      that androgens have a role in sex-related differences of the activities in liver
      microsomes of male and female rats. Furthermore, sex-related differences of the
      activities were examined in microsomes and cytosol from the liver and kidney of
      the rat, mouse, hamster, guinea pig, and rabbit. All animal species tested showed
      sex-related differences in their activities. The rat and rabbit were found to
      resemble the guinea pig and hamster, respectively, in the occurrence of sex
      related difference.

PMID- 8272570
TI  - Metabolism of trimipramine in vitro by human CYP2D6 isozyme.
AB  - In vitro metabolism of the tricyclic antidepressant trimipramine using a
      commercial preparation of human CYP2D6 isozyme expressed in a human cell line is
      described. 2-Hydroxytrimipramine and a previously unreported metabolite, 2,10- or
      2,11-dihydroxytrimipramine were isolated. Their structures were determined by gas
      chromatography/mass spectroscopy of underivatized and derivatized extracts.
      Acetylation of the new metabolite resulted in dehydration at C10 to give 10,11
      dehydro-2-acetoxytrimipramine. No N-dealkylation of trimipramine was observed.
      Prior administration of quinidine produced a large reduction in the metabolic
      oxidation of trimipramine with CYP2D6 while prior administration of quinine had
      no effect. The use of this CYP2D6 isozyme preparation in vitro is of value in the
      identification of possible in vivo substrates for the human CYP2D6 isozyme.

PMID- 8272571
TI  - Effect of gossypol on 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase
      activities in adult rat testes.
AB  - It has been reported that little to no 5 alpha-reductase can be detected in adult
      rat testes when progesterone is used as substrate. The 5 alpha-reductase activity
      in 4-month-old rats and the inhibitory action of gossypol on steroidobiosynthesis
      were studied. Testicular sections (10 microns thickness) were incubated at 30.5
      degrees C in the presence of NADPH with 3H-testosterone and cold testosterone as
      substrates (9 microM total), and with or without gossypol as the test sample and
      control, respectively. Endogenous testosterone level was evaluated by
      radioimmunoassay. Reverse phase high performance liquid chromatography (HPLC) was
      used to separate the substrate and products. Components of interest were
      collected and their recovery monitored. At 200 microM concentration, gossypol
      significantly decreased dihydrotestosterone (DHT) formation by 21% when compared
      to that of control (0.6 pm/mg protein/min), and decreased 5 alpha-androstane-3
      alpha,17 beta-diol formation by 35% vs control (2 pm/mg protein/min). In the
      current study, gossypol was found to have inhibitory effects of noncompetitive
      nature on 5 alpha-reductase, which catalyzes the conversion of testosterone to
      DHT, and on 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), which
      interconverts DHT and dihydroandrostanediol.

PMID- 8272572
TI  - The inhibitory actions of protease inhibitors on the production of
      polymorphonuclear leukocyte elastase and interleukin 8.
AB  - The inhibitory actions of Ulinastatin, which is a protease inhibitor, on the
      production of polymorphonuclear leukocyte elastase (PMN-elastase) and interleukin
      8 (IL-8) in vascular endothelial cells were evaluated. Our findings suggest that
      IL-8 plays a role in the production of PMN-elastase. Ulinastatin inhibited the
      lipopolysaccharide (LPS)-stimulated activity of polymorphonuclear leukocytes
      (PMN) and the production of IL-8 in vascular endothelial cells. Ulinastatin also
      inhibited the LPS-stimulated production of PMN-elastase in PMN.

PMID- 8272573
TI  - Estrogen and androgen receptors in aorta of the rabbit and regulation by estrogen
      and androgen.
AB  - This study was designed to investigate the sexual and/or regional dimorphism of
      the effects of estrogens and androgens on the aorta. Estrogen, estradiol-17 beta
      (E2) and estriol (E3), or androgen, dihydrotestosterone (DHT) and testosterone
      (T), binding levels, and of effects of E2 and T on their levels were determined
      in aortas of the male and female rabbits. Priming with E2 affected estrogen
      binding levels of the male aorta, but the physiological condition with E2 plus T
      induced the levels of E2 and E3 receptors in the female aorta. DHT receptor level
      in the male was increased with E2 alone or with T, while a rise in T binding
      level was seen in the male and female primed with E2 and T. These findings
      suggest that there is a sexual and/or regional dimorphism in the actions of
      estrogen and androgen on their receptor synthesis in the aorta.

PMID- 8272574
TI  - Preventive effect of gamma-glutamylcysteinylethyl ester on immunological cell
      injury in isolated rat hepatocytes with anti-rat liver plasma membrane antiserum
      treatment.
AB  - We studied the mechanism by which gamma-glutamylcysteinylethyl ester (gamma-GCE),
      which is rapidly transported into hepatocytes and converted to reduced
      glutathione (GSH), prevents immunological hepatic injury. The effect of gamma-GCE
      on cell injury, as estimated by release of transaminases from cells, and changes
      in phospholipase A2 (PLA2) activity and of GSH, Ca2+, and lipid peroxide (LPO)
      contents were examined in isolated rat hepatocytes treated with anti-rat liver
      plasma membrane rabbit antiserum (ALPMA) and compared with that of GSH. gamma-GCE
      prevented not only the release of transaminases from hepatocytes treated with
      ALPMA but also a decrease in GSH content, activation of PLA2, and increases in
      Ca2+ and LPO contents in the damaged hepatocytes. However, the preventive effect
      of GSH on these changes was weaker than that of gamma-GCE. In addition, gamma-GCE
      prevented the development of cell injury in ALPMA-pretreated hepatocytes. These
      results suggest that gamma-GCE prevents immunological cell injury in ALPMA
      treated rat hepatocytes mainly by maintaining the integrity of the plasma
      membrane through its conversion to GSH within the cells.

PMID- 8272575
TI  - Morphological changes in the hearts of CD1 mice following chronic treatment with
      doxorubicin and lonidamine.
AB  - CD1 female mice were treated with doxorubicin (DXR, 5 mg/Kg i.v.) once a week for
      eight weeks or with lonidamine (LND, 100 mg/Kg i.p.) once a week for eight weeks.
      Other mice received lonidamine (100 mg/Kg i.p.) immediately before doxorubicin (5
      mg/Kg i.v.) administration. The animals were sacrificed four weeks after the last
      administration and their cardiac morphology was evaluated by means of light
      microscopy. Lonidamine slightly reduced the extent of the atrial but not of the
      ventricular alterations caused by DXR. The results seem to indicate that, in this
      experimental model, lonidamine does not substantially modify the cardiotoxicity
      induced by doxorubicin.

PMID- 8272577
TI  - Pleural pressure measured with a rib capsule in anesthetized pneumonectomized
      rabbits.
AB  - Pleural pressure was measured at end expiration in anesthetized rabbits using a
      rib capsule placed in the right fifth rib. Three groups of rabbits were studied
      in right and left lateral recumbency at least 8 weeks after surgery; rabbits that
      had undergone left pneumonectomy (Px, n = 8), rabbits that had undergone left
      pneumonectomy with wax plombage (Px + W, n = 7), and sham-operated control
      rabbits (S, n = 6). In S, Px, and Px + W rabbits in the left lateral position
      (lung and capsule nondependent), pleural pressure was -2.11 +/- 0.88 (mean +/-
      SD), -2.65 +/- 0.23, and -1.96 +/- 0.55 cmH2O respectively. In S, Px and Px + W
      rabbits in the right lateral position (lung and capsule dependent), pleural
      pressure was 0.64 +/- 0.22, 0.85 +/- 1.42, and 0.48 +/- 1.77 cmH2O respectively.
      In each position, pleural pressure did not differ among groups. This suggests
      that the compensatory increase in lung volume and reduced lung compliance
      following pneumonectomy in rabbits (Olson, J. Appl. Physiol. 74: 415-422, 1993)
      was not simply due to hyperinflation of the remaining lung.

PMID- 8272576
TI  - The effect of VA-045 on disturbance in consciousness in experimental animal
      models.
AB  - The effect of VA-045, a novel apovincaminic acid derivative, on disturbance in
      consciousness was investigated in mice and rats. VA-045 and thyrotropin-releasing
      hormone (TRH) shortened the duration of pentobarbital-induced sleeping in rats.
      VA-045 and TRH improved head impact-induced disturbed behavior in mice. The
      duration of action of the improving effect of VA-045 was longer than that of TRH.
      VA-045 and TRH also ameliorated the global cerebral ischemia-induced neurological
      deficits. Global cerebral ischemia was produced by a 10 min occlusion of both
      common carotid arteries 24 hr after the permanent electrocauterization of
      bilateral vertebral arteries. VA-045, but not TRH, attenuated the global cerebral
      ischemia-induced decreased step through latency (STL) in a passive avoidance task
      in rats. TRH enhanced spontaneous locomotor activity in mice, whereas VA-045 had
      no effect on it. The pharmacological effects of VA-045 on disturbance in
      consciousness will be discussed.

PMID- 8272578
TI  - Relationship between whole blood base excess and CO2 content in vivo.
AB  - Empirical relationships are demonstrated for whole blood base excess (BE) and CO2
      content (CCO2), both calculated from in vivo measurements of PCO2, pH, hemoglobin
      concentration and O2 saturation. Comparisons are provided by measurements from
      three separate studies: (1) supine exercise (arterial and mixed venous samples);
      (2) chronic obstructive disease patients (arterial samples) breathing air and
      100% O2; and (3) maximal seated exercise on a bicycle ergometer with and without
      added inspired CO2 (arterial samples before, during and after). Two standardized
      values of CCO2 (vol.%) are derived which closely relate to BE (mmol/l). The CCO2
      at a PCO2 of 40 mmHG [CCO2(40)] for all samples (n = 220) demonstrated a
      curvilinear relationship: CCO2 (40) = 45.37 + 1.48(BE) + 0.0156(BE)2, r = +
      0.996, SEE = 0.88 vol.%. The CCO2 at a pH of 7.4 [CCO2(7.4)] gave a linear
      relationship: CCO2(7.4) = 45.09 + 2.58(BE), r = + 0.998, SEE = 1.19 vol.%.
      Empirical computations for the Haldane factor from studies 1 and 2 gave values of
      0.285 in terms of CCO2 (vol.%/vol.%) and 0.266 for BE (mmol/l/mmol reduced Hb).
      The BE values can serve as useful estimates of lactate concentrations during
      exercise and the excellent relationships between standardized CCO2 and BE
      demonstrate their equivalency and either can be utilized, depending on whether
      quantification of the CO2 dissociation curve or acid-base status is desired.

PMID- 8272579
TI  - The role of surfactant in the static lung mechanics of the lizard Ctenophorus
      nuchalis.
AB  - We previously showed that the lung of the central Australian lizard, Ctenophorus
      nuchalis, contains a large amount of surfactant, the composition of which varies
      with body temperature. We now show that the specific compliance of the lungs of
      these lizards remains constant regardless of whether they were maintained at 10,
      18, 27, 37 or 43 degrees C for 4 hours. In contrast, the opening pressure was
      constant up to 27 degrees C, but decreased at 37 and 43 degrees C. When we
      lavaged the lungs in situ to remove the majority of surfactant, specific
      compliance decreased while opening pressure increased. The lungs of C. nuchalis
      are essentially two bubbles, with the left one larger at low and intermediate
      volumes. After collapsing both lungs, the larger left lung always inflated first.
      However, following lavage the smaller right lung inflated first. As the larger
      lung, when collapsed, would have a much greater area of epithelial contact, this
      result is consistent with surfactant acting as an 'antiglue'. During deflation
      the smaller lung collapsed first, consistent with the law of Laplace. Compliance
      did not change in the saline-filled lung suggesting that the gas-liquid interface
      does not play a major role. We conclude that in the lungs of these lizards,
      surfactant is acting as an antiglue. This might be important during periods of
      apnea at low body temperatures, when residual volume is small and epithelial
      surfaces may come into contact.

PMID- 8272580
TI  - Responses of respiratory modulated and tonic units in the retrotrapezoid nucleus
      to CO2.
AB  - We hypothesized that the retrotrapezoid nucleus (RTN) contains both respiratory
      modulated (RM) and non-respiratory modulated (NRM) neurons which participate in
      the ventilatory response to increased CO2. We made extracellular recordings of
      the activity of 46 single units in the RTN of 9 decerebrate, paralyzed,
      ventilated cats (5 intact; 4 with carotid body and sinus ablation) under eucapnic
      (PCO2 = 34.2 +/- 3.5 mmHg; mean +/- SD) and hypercapnic (PCO2 = 47.4 +/- 3.4
      conditions. To define a RM unit, we used the eta 2 statistic which is the ratio
      of the variance of the unit firing rate within respiratory cycles to that across
      respiratory cycles. We classified the units as RM (N = 17) if the eta 2 values in
      eucapnia or hypercapnia were > or = 0.25 and as NRM (N = 29) if the values were <
      0.25. Overall, 19/46 units (41%) increased their firing rate with increased CO2,
      5 decreased their firing rate, and 22 had no significant change in firing rate.
      Of 17 RM units, 8 (47%) increased their mean firing rate with hypercapnia from
      7.6 +/- 3.9 to 23.2 +/- 6.8 spikes/sec. These included 5 inspiratory units, 2
      inspiratory units that had an onset of firing in late expiration (Pre-I/I), and 1
      expiratory unit. Seven of these also changed their discharge pattern (eucapnic
      eta 2 = 0.02 to 0.12; hypercapnic eta 2 = 0.34 to 0.79) Of 29 NRM units, 11 (38%)
      showed a significant increase in mean firing rate with CO2 stimulation from 19.8
      +/- 7.2 to 31.3 +/- 8.2 spikes/sec. The RTN has RM units which change their
      discharge pattern and firing rate in response to increased CO2, as do units
      within the medulla and pons, and it has NRM units which are also responsive to
      increased CO2. These data indicate that some neurons of the RTN are involved in
      the central chemoreceptor response but they provide no direct evidence that
      chemoreception resides within the RTN.

PMID- 8272581
TI  - Effects of midazolam and flumazenil on ventilation during sustained hypoxia in
      humans.
AB  - The purpose of this study was to investigate whether increases in gamma
      aminobutyric acid (GABA) in the brain stem underlie the ventilatory decline
      observed during hypoxia in man. The ventilatory responses to sustained isocapnic
      hypoxia were studied in six adult male subjects on three separate days in three
      pharmacological conditions: (1) without any drug administration; (2) during
      infusion of midazolam (a drug which potentiates the effect of GABA); and (3)
      during infusion of flumazenil (a benzodiazepine antagonist). On each experimental
      day, the following protocol was repeated three times: end-tidal PO2 was held at
      100 Torr for 10 min, then at 50 Torr for 20 min and finally at 100 Torr for 5
      min. End-tidal PCO2 was held constant throughout. Responses in the three
      pharmacological conditions were similar. We conclude that neither potentiation of
      GABA transmission (midazolam) nor antagonism of this potentiation (flumazenil)
      greatly affect the decline in ventilation which occurs during extended exposure
      to hypoxia.

PMID- 8272582
TI  - Effects of left atrial and airway pressures on airway blood flow.
AB  - The blood flow contributions of the pulmonary and systemic circulations to airway
      blood flow from the trachea down to the 5th generation airways when either 15
      cmH2O positive end expiratory pressure (PEEP) or 20 mmHg left atrial pressure was
      applied were assessed in anesthetized dogs by injecting 15-microns radiolabeled
      microspheres into the right and left heart, respectively. After the microsphere
      injections, the animals were killed, and the tracheal cartilage, tracheal muscle
      mucosa, main bronchi and the 2nd generation bronchi down to the 5th generation
      airways were excised and collected for radioactive counting. The results of this
      study showed that under normal conditions, tracheal blood flow was primarily
      systemic (> 95% of total tracheal blood flow) averaging 15-26 ml.min-1 x (100 g)
      1, while both the pulmonary [10 ml.min-1 x (100 g)-1] and systemic circulations
      [15 ml.min-1 x (100 g)-1] contributed substantially to main bronchi blood flow.
      The systemic blood flow contribution to the lower airway generations (2nd to the
      5th generation airways) stayed relatively constant, averaging 13-31 ml.min.(100
      g)-1 while the pulmonary blood flow contribution increased significantly in these
      airway segments to a maximum of over 100 ml.min-1 x (100 g)-1 at the 5th
      generation. At 15 cmH2O PEEP, the systemic contribution to all of the airway
      segments (except the 5th generation, P < 0.09) and the pulmonary component to the
      main bronchi, significantly decreased (P < 0.05). In contrast, elevated left
      atrial pressure had little effect on the pulmonary and systemic contributions to
      airway blood flow. The results of this study suggest that elevated PEEP has a
      greater effect than elevated left atrial pressure on the systemic blood flow
      contribution to the airways, while the pulmonary blood flow contribution to the
      airways is affected very little by either of these perturbations.

PMID- 8272583
TI  - The HPV response is different with constant pressure vs constant flow perfusion.
AB  - Hypoxic pulmonary vasoconstriction (HPV) may be manifest in one of two ways:
      either an increase in the pulmonary artery pressure, or flow diversion away from
      the portion of the pulmonary bed with reduced conductance. We tested the
      hypothesis that the magnitude of the HPV response differs under conditions of
      constant flow perfusion, where pulmonary artery pressure (Ppa) rises during
      hypoxia, vs conditions of constant pressure perfusion, where Ppa remains constant
      and flow (Q) is diverted away from the lungs during hypoxia. In isolated,
      perfused rabbit lungs, the HPV response to four levels of hypoxia (12, 6, 3 and
      0% oxygen) was of greater magnitude and more sustained under conditions of
      constant pressure perfusion as compared to constant flow perfusion. The possible
      significance of these findings as they relate to interpretation of studies in
      both the perinatal and mature pulmonary circulation is discussed.

PMID- 8272584
TI  - Local pulmonary blood flow: control and gas exchange.
AB  - We studied the local response of the pulmonary vasculature to combined changes in
      alveolar PO2 and PCO2 in the right apical lobe (RAL) of six conscious sheep. That
      lobe inspired an O2-CO2-N2 mixture adjusted to produce one of 12 alveolar gas
      compositions: end-tidal PCO2 (PETCO2) of 40, 50, and 60 Torr, each coupled with
      end-tidal PO2 (PETO2) of 100, 75, 50, and 25 Torr. In addition, at each of the
      four PETO2, the inspired CO2 was set to 0 and PETCO2 was allowed to vary as RAL
      perfusion changed. The remainder of the lung, which served as control (CL)
      inspired air. Fraction of the total pulmonary blood flow going to the RAL (%QRAL)
      was obtained by comparing the methane elimination from the RAL to that of the
      whole lung, and expressed as a percentage of that fraction at PETCO2 = 40, PETO2
      = 100. Cardiac output, pulmonary vascular pressures, and CL gas tensions were
      unaffected or only minimally affected by changes in RAL gas composition. A drop
      in PO2 from 100 to 50 Torr decreased local blood flow by 60% in normocapnia and
      by 66% at a PCO2 of 60. At all levels of oxygenation, an increase in PCO2 from 40
      to 60 reduced QRAL by nearly 50%. With these stimulus-response data, we developed
      a model of gas exchange, which takes into account the effects of test segment
      size on blood flow diversion. This model predicts that: (1) when the ventilation
      to one compartment of a two compartment lung is progressively decreased, PAO2
      remains above 60 Torr for up to 60% reductions in alveolar ventilation,
      irrespective of compartment size; (2) the decrease in PAO2 that occurs at
      altitude is accompanied by a drop in PACO2 that limits the decrease in
      conductance and minimizes the pulmonary hypertension; and (3) as we stand, local
      blood flow control by the alveolar gas tensions halves the alveolar-arterial PO2
      and PCO2 differences imposed by gravity.

PMID- 8272585
TI  - Evidence for an intramuscular ventilatory stimulus during dynamic exercise in
      man.
AB  - During incremental work rate exercise, ventilation (VE) typically increases in
      proportion to the metabolic rate until the onset of a progressive metabolic
      acidemia induces an additional compensatory hyperpnea. We examined the control
      characteristics of this compensatory mechanism in seven healthy subjects
      performing incremental cycle ergometry to their limit of tolerance at different
      levels of lower-body positive pressure (LBPP) at 0, 15, 30, and 45 Torr in order
      to determine if LBPP could alter the occurrence of the ventilatory threshold.
      Ventilatory responses and pulmonary gas exchange variables were measured breath
      by-breath while 'arterialized'-venous blood was sampled from the dorsum of the
      heated hand for determination of [lactate], pH, and [K+]. The ventilatory
      threshold was progressively reduced with increasing levels of LBPP: Ventilatory
      threshold = 2.33-(0.0173.LBPP); (r2 = 0.59, P < 0.001). Ventilatory equivalents
      for oxygen (VE/VO2) and carbon dioxide (VE/VCO2) were systematically elevated at
      work rates above 50 W by increases in respiratory frequency which also resulted
      in lower PETCO2 and higher PETO2 values. As [lactate] was only slightly elevated
      above control (delta lactate < 1 mEq.L-1) while pH and [K+] were unchanged, it
      seems unlikely that the LBPP-induced hyperpnea can be attributed to activation of
      peripheral arterial or central chemoreceptors. These findings suggest a
      ventilatory stimulus may be generated by an LBPP-induced reduction in perfusion
      with the subsequent accumulation of intramuscular metabolites at the working limb
      and/or a direct effect of increased intramuscular tissue pressure.

PMID- 8272586
TI  - Femoral vascular occlusion and ventilation during recovery from heavy exercise.
AB  - Ventilation and cardiac output subside gradually following cessation of exercise,
      which is commonly linked to the slow wash-out of materials from the recovering
      muscles. The effect of hindering the removal of the metabolic products of heavy
      cycle exercise on the kinetics of ventilation and gas exchange was studied in 5
      subjects by occluding the femoral circulation with cuffs during the first 2 min
      of recovery (15 tests). Fifteen undisturbed recoveries served as controls.
      Compared to spontaneous recovery, circulatory obstruction induced an immediate
      (from the first breath) decrease in minute ventilation (VE), while end-tidal CO2
      (PETCO2) as well as lactate and K+ in venous blood at forearm did not change
      significantly. A ventilatory deficit of 27 +/- 9 L was observed from the 2 min of
      occlusion. Following cuff deflation, VE rose 2-3 breaths after PETCO2 began to
      increase in every subject. The mechanisms of the normocapnic reduction of VE
      during occlusion, as well as the rise of ventilation following cuff release, are
      still unclear. However, these results argue against any significant role for
      hyperpnea-inducing intramuscular chemoreception, or point to muscular perfusion
      as a prerequisite of such a mechanism to operate.

PMID- 8272587
TI  - Pulmonary chemoreflex and phrenic sympathetic efferents.
AB  - The pulmonary chemoreflex components such as reactions of phrenic sympathetic
      neuron (PhSN) activity, phrenic nerve activity, heart rate and blood pressure
      were tested in chloralose-anesthetized, paralyzed cats. 10 micrograms to 160
      micrograms phenylbiguanide (PBG) in 0.9% NaCl was injected into the pulmonary
      circulation. PBG injected into the right atrium (in 11 of 19 experiments) and
      into the pulmonary artery (in 5 of 8 experiments), evoked short-latency (1-1.4
      sec) dose-dependent increase in PhSN activity accompanied by increase in blood
      pressure, and followed by decrease in these two variables. In all experiments,
      activity of the phrenic nerve was depressed, and bradycardia occurred after PBG
      injection. All responses to PBG injections into the pulmonary artery were
      abolished following bilateral vagotomy. In the same procedure related to the
      right atrium after vagotomy, the increases in PhSN activity and blood pressure
      were also abolished, although a decrease in heart rate, PhSN activity and in the
      amplitude of phrenic nerve discharges together with an increase in their
      frequency persisted. Our results suggest that short-latency increase in PhSN
      activity is a component of pulmonary chemoreflex.

PMID- 8272588
TI  - Effects of low intrapulmonary PCO2 on ventilatory sensitivity to PaCO2 in
      chickens.
AB  - We found conflicting reports regarding the relationship between intrapulmonary
      PCO2 and sensitivity to PaCO2 in the chicken. To resolve this, we anesthetized
      eight cockerels with sodium pentobarbital (25-35 mg/kg), cannulated the cutaneous
      ulnar vein and carotid artery, opened the thorax and ventilated right and left
      lungs independently. We established PaCO2 by over-ventilating the denervated,
      perfused right lung with the following: 94.7, 39.9, 31.6 and 19.0 Torr PCO2
      balanced with oxygen. At each right lung CO2 tension (PRCO2), we measured blood
      pressure and ventilatory responses to five CO2 tensions (PLCO2) ventilating the
      non-perfused left lung. PLCO2 ranged from 70.3 to 15.7 Torr. We found a linear
      relationship between the amplitude of sternal deflections and PaCO2-1, and that
      the slope depended upon PLCO2. Respiratory period was also linearly related to
      PaCO2-1, however the intercept, not the slope, was a altered by PLCO2. Stepwise
      regression analyses revealed an important interaction term (that is,
      (PaCO2.PLCO2)-1) in the determination of respiratory amplitude, but not in the
      determination of period. We conclude that low intrapulmonary PCO2 enhances the
      sensitivity of respiratory amplitude to changes in PaCO2. Further, we propose
      that intrapulmonary chemoreceptor discharge mediates this change in sensitivity
      to PaCO2.

PMID- 8272589
TI  - Respiratory and cardiovascular responses to hypoxia in the Australian lungfish.
AB  - Simultaneous measurements of pulmonary blood flow (qPA), coeliacomesenteric blood
      flow (qCoA), dorsal aortic blood pressure (PDA), heart rate (fH) and branchial
      ventilation frequency (fv) were made in the Australian lungfish, Neoceratodus
      forsteri, during air breathing and aquatic hypoxia. The cholinergic and
      adrenergic influences on the cardiovascular system were investigated during
      normoxia using pharmacological agents, and the presence of catecholamines and
      serotonin in different tissues was investigated using histochemistry. Air
      breathing rarely occurred during normoxia but when it did, it was always
      associated with increased pulmonary blood flow. The pulmonary vasculature is
      influenced by both a cholinergic and adrenergic tonus whereas the
      coeliacomesenteric vasculature is influenced by a beta-adrenergic vasodilator
      mechanism. No adrenergic nerve fibers could be demonstrated in Neoceratodus but
      catecholamine-containing endothelial cells were found in the atrium of the heart.
      In addition, serotonin-immunoreactive cells were demonstrated in the pulmonary
      epithelium. The most prominent response to aquatic hypoxia was an increase in
      gill breathing frequency followed by an increased number of air breaths together
      with increased pulmonary blood flow. It is clear from the present investigation
      that Neoceratodus is able to match cardiovascular performance to meet the changes
      in respiration during hypoxia.

PMID- 8272590
TI  - Hyperosmolality alters the ventilatory response to acute hypercapnia and hypoxia.
AB  - Acute hyperosmolality in the Pekin duck results in an extracellular acidosis and
      hypercarbia without any stimulation of ventilation. The development of the
      extracellular acidosis is accompanied by the concurrent development of an
      intracellular alkalosis systemically which has been hypothesized to depress
      ventilation (Kasserra et al., J. Appl. Physiol., 1993). In order to investigate
      this apparent suppression of ventilation, the ventilatory response to various
      respiratory challenges (CO2, O2, K+) was studied both before (normosmotic) and
      after (hyperosmotic) hypertonic sucrose infusion. Increased plasma osmolality
      caused a significant drop in arterial pH of 0.06 +/- 0.01 units and a 4 Torr
      increase in PaCO2, yet did not stimulate any significant increase in ventilation
      despite a significant increase in oxygen consumption. Acute hyperosmolality
      increased the PaCO2 associated with resting ventilation, and decreased the
      magnitude of the ventilatory response to a given increase in PaCO2, compared with
      the response to the same ventilatory challenge in normosmotic animals. Acute
      hyperosmolality increased the ventilatory response to hypoxia and K+ compared
      with normosmotic animals. The opposite effect of hyperosmolality on the
      ventilatory responses to hypercapnia compared with hypoxia suggests that the
      mechanisms of chemoreception for hypercapnia and hypoxia are different. The
      depressed ventilatory response curve to increased PaCO2 and decreased arterial pH
      during hyperosmolality, both alone and during the hypercapnic challenge, suggests
      that the peripheral chemoreceptor response to pH and CO2 is suppressed. It is
      hypothesized that the suppression results from the intracellular alkalosis
      occurring during acute hyperosmolality.

PMID- 8272591
TI  - Local blood flow is not linked to lactate within single rabbit skeletal muscles.
AB  - A marked regional distribution in blood flow within single skeletal muscles on a
      non-microvascular level, i.e. at the level of large arterioles or small arteries,
      is present in dog, cat and rabbit. The mechanism for this perfusion pattern is
      not known. The goal of the present study was to see if regional blood flow was
      correlated to regional lactate metabolism. Anesthetized rabbits were studied.
      Blood flow to 0.25 g muscle samples was measured with microspheres whereas
      lactate content and lactate dehydrogenase activity were determined in extracts of
      these samples. No correlation was detected between regional blood flow and
      regional lactate or lactate dehydrogenase either at rest or during exercise
      hyperemia. Expressed as the coefficient of variation (CVc), regional blood flow
      showed a marked scatter, the CVc ranged from 0.32 to 0.35. The corresponding CVc
      for both lactate and lactate dehydrogenase activity ranged from 0.16 to 0.19. It
      is concluded that regional blood flow is not correlated to regional lactate
      metabolism. The regional distribution in blood flow was markedly more uneven than
      that for lactate content and for lactate dehydrogenase activity.

PMID- 8272592
TI  - Capillarisation and fibre types in hypertrophied m. plantaris in rats of various
      ages.
AB  - Influences of age, overload obtained through denervation of synergists, and
      training on the capillarisation of the m. plantaris were compared in 5-, 13- and
      25-month-old rats in relation to different fibre types. Overload resulted in
      about 30% hypertrophy in each age group. Age effects were significant only in the
      deep (more oxidative) region of the muscle. From 5 to 13 months, the percentage
      of FOG fibres increased at the expense of FG fibres, while the fibre cross
      sectional areas (FCSA) of each fibre type increased. From 13 to 25 months, the
      FCSA of FG fibres decreased, as did the local capillary-to-fibre ratio (LCFR) of
      each fibre type, indicating capillary loss and a declined capillary density for
      each fibre type (CFD). Overload effects were identical for both the superficial
      (more glycolytic) and the deep region for each age group. With overload, FCSA and
      LCFR of each fibre type increased, while CFD decreased, indicating that capillary
      proliferation occurred with overload, even at old age, although lagging behind
      increases in FCSAs. Training showed minor effects.

PMID- 8272593
TI  - CO reveals dual mechanisms of O2 chemoreception in the cat carotid body.
AB  - The hypothesis that CO-binding pigments in the carotid body participate in O2
      chemoreception was tested. The chemosensory nerve discharges of cat carotid body
      perfused and superfused in vitro at 36-37 degrees C with cell-free solution
      containing CO2-HCO3- (pH approximately equal to 7.39) were recorded to monitor O2
      chemoreception. Several levels of PCO (60-550 Torr) at two levels of PO2 (50 Torr
      140 Torr) were used. With high PCO of 500-550 Torr at any PO2 the discharge rate
      peaked promptly but the effect was significantly less than that to hypoxia. At
      any stage of the CO effect, exposure to light promptly attenuated or eliminated
      the response, as if the stimulatory effect of hypoxia was absent. Lower PCO of 60
      70 Torr attenuated the response to hypoxia which was not suppressed by light. PCO
      of 140 Torr also attenuated the response to hypoxia and made the activity
      partially photolabile. During high PCO exposure the excitatory response to
      cyanide but not to nicotine was attenuated, consistent with the idea that the
      effects of nicotine are downstream from those of CO. Both inhibitory and
      excitatory effects of CO were promptly reversible. The results indicate that two
      types of CO-binding chromophores participate in O2 chemoreception in the carotid
      body.

PMID- 8272594
TI  - Differential diagnosis of progressive flaccid weakness.

PMID- 8272595
TI  - Distal myopathies and dystrophies.

PMID- 8272596
TI  - Inclusion body myositis: new concepts.

PMID- 8272597
TI  - Clinical syndromes associated with anti-GM1 antibodies.

PMID- 8272598
TI  - Motor neuropathy with multifocal conduction block.
AB  - Our present understanding of the syndromes of CIDP and MMN is insufficient to
      separate them clearly. I believe that MMN is simply a multifocal, predominantly
      motor variant of CIDP. Furthermore, the highly touted resemblance of MMN to MND
      has been exaggerated; these syndromes are only superficially similar and can
      readily be distinguished on clinical and electrophysiologic grounds. MMN is rare
      but is probably more common than initially believed; certainly, the literature is
      replete with reports of cases. Further studies are needed to clarify fully the
      relationship between CIDP and MMN and the role of glycolipid antibodies in MMN
      and other motor syndromes.

PMID- 8272599
TI  - Progress toward cloning of the gene responsible for childhood spinal muscular
      atrophy.

PMID- 8272600
TI  - Post-polio syndrome: an update.
AB  - The PPS is now a well-recognized entity encompassing the late manifestations that
      occur because of previous poliomyelitis. Common signs and symptoms include
      fatigue, cold intolerance, joint deteriorations with pain, and prominent
      neurologic problems that include new weakness, muscle pain, atrophy, respiratory
      insufficiency, dysphagia, and sleep apnea. It is estimated that there are 1.63
      million polio survivors in the United States and that half of them will develop
      PPS. PPS and PPMA usually begin 30 to 40 years after the acute illness and are
      very slowly progressive. The etiology is unclear, although premature exhaustion
      of the new sprouts that develop after acute poliomyelitis and of their motor
      neurons appears most likely. Less likely is a persistent polio-virus infection or
      an immune-mediated problem. Treatment is primarily supportive, although
      nonfatiguing strengthening exercise may improve strength over the short term. The
      long-term effects of this type of exercise remain to be clarified.

PMID- 8272601
TI  - Paraneoplastic syndromes and progressive motor dysfunction.

PMID- 8272602
TI  - The progressive paralytic disorders associated with Lyme disease.
AB  - The clinical disorders of B. burgdorferi infection continue to be elucidated. The
      neurologic disorders, especially those that produce progressive paralytic
      syndromes, have been reasonably well described. They frequently occur in
      conjunction with syndromes affecting other body systems. The appropriate use of
      antibiotics is usually effective in eradicating the infection. However, some
      individuals may have residual deficits as a result of the infectious process,
      even after the bacterial infection is eradicated. These are treated by
      appropriate supportive and symptomatic therapies, not by endless, useless courses
      of antibiotics. Finally, although early discussions of the pathophysiology and
      the clinical syndromes associated with B. burgdorferi infection compared the
      neurologic syndromes of with those of T. pallidum, raising the specter of another
      Great Imitator, this frame of reference has lost its usefulness. Modern
      laboratory techniques have allowed much better definition of the syndromes
      associated with this disorder. Whereas I once subscribed to the slogan, "Remember
      the Great Imitator," I now recommend that neurologists "Imitate Great Thinkers
      and Forget the Great Imitator."

PMID- 8272603
TI  - Chronic inflammatory demyelinating polyneuropathy.

PMID- 8272604
TI  - My fearful symmetry.

PMID- 8272605
TI  - [The diagnosis of chronic Chagas disease using recombinant antigens of
      Trypanosoma cruzi].
AB  - A panel of eight recombinant Trypanosoma cruzi antigens was used to study the IgG
      reactivity of sera proceeding from 151 patients with chronic Chagas disease.
      These samples were reactive against T Cruzi epimastigotes by immunofluorescence
      and enzyme linked assays. A dot blot assay was performed to evaluate the
      reactivity against recombinant clones 1, 2, 13, 26, 30, 36, 54 and SAPA (Shed
      Acute Phase Antigen). Ninety six percent of samples reacted against one or more
      of these antigens. The most frequently recognized proteins were clones 1, 2, 13,
      36 and 26 with 90, 89, 76, 71 and 66 percent of reactivity respectively. Less
      than 50% of sera reacted against clones 30, 54 and SAPA. Sera from symptomatic
      patients had a significantly higher frequency of reactivity against clone SAPA
      than those from asymptomatic patients. This difference suggests that a high
      reactivity against clone SAPA may be related to acute infections and symptoms. No
      significant relationship could be established between specific recombinant clone
      recognitions and particular clinical forms of the disease (cardiological or
      digestive). It is concluded that these recombinant proteins may become a good
      tool for the evaluation of the immune response of patients infected with T.
      cruzi.

PMID- 8272606
TI  - [Changes in ethical attitudes during medical studies].
AB  - The aim of this work was to explore the attitude changes towards ethico-medical
      issues in medical students as they went through medical school. A personal
      standardized questionnaire containing 14 closed and direct questions was applied
      to 27 freshmen, 38 interns and 14 post graduates. The most outstanding
      differences in ethical attitudes occurred between first year students and the
      older groups. The younger students adhered to ethical principles, valued justice
      towards patients and moral integrity in physicians. The older students and post
      graduates emphasized the professional role of physicians and preferred
      institutional ethical regulations over public control. They also considered more
      valuable therapeutic efficiency and paternal attitudes towards patients as well
      as social prestige and economical rewards. We conclude that there is a
      progressive erosion of humanistic principles along the medical studies, that are
      substituted by a model of professional competence, social recognition and
      internal ethical control.

PMID- 8272607
TI  - [MN blood group and congenital malformations].
AB  - This work analyzes the mother-son segregation of MN blood group in malformed and
      normal newborns. MN blood group was measured in 90 malformed, 70 paired normal
      newborns and their respective mothers, at the Maternity of the University of
      Chile Clinical Hospital. The expected values for the different mother-child pairs
      were calculated according to the ITO matrix method, using maximally probable
      appraisers. Among malformed newborns, there was an excess of heterozygous sons
      when the mother was homozygous for the MN system. Among malformed males, there
      was an excess of MM-MN and MN-MM mother-son pairs. Among control newborns, no
      distortions were found. These results suggest that there is a strong association
      between MN heterozygosis, sex and congenital malformations.

PMID- 8272608
TI  - [Cleft lip and palate in the Chilean population: association with BamH1
      polymorphism of the transforming growth factor alpha (TGFA) gene].
AB  - In recent studies we have demonstrated that the model that better explains the
      genetic etiology of non syndromic cleft lip/palate (CL/P) in the Chilean
      population is one that postulates the existence of a major dominant autosomic
      locus with low penetrance, without discarding the possible influence of
      polygenes. Similar conclusions have been communicated by others authors in
      different populations. Thus, investigations have been initiated to seek possible
      associations between candidate genes and restriction length polymorphisms
      (RFLP's), specifically between Transforming Growth Factor Alpha (TGFA) gene
      RFLP's and CL/P, in caucasian populations. Results thus far obtained have been
      inconclusive. Therefore, the aim of this work was to study this association in
      the Chilean population, that is ethnically different. The gene and phenotype
      frequencies of the TGFA gene BamH1 polymorphism in CL/P probands (n = 21) and
      controls (n = 16) were determined. No significant differences were detected in
      the frequencies of the A1 and A2 alleles of the TGFA gene between probands and
      controls. These results do not support an association between the cleft palate
      phenotype and TGFA RFLP.

PMID- 8272609
TI  - [Medical liability lawsuits according to specialties in Chile].
AB  - One-hundred forty-five cases of medical liability lawsuits originating in Chile
      from January 1987 to June 1991 and studied at the Medico Legal Service, were
      reviewed. A persistent increase in the number of accusations is observed in these
      five years. The principal medical specialties involved are Obstetrics and
      Gynecology (32%), General Surgery (18%), Internal Medicine (15%) and Pediatrics
      (9%). Seventy seven percent of implicated physicians were accredited specialists.
      Fifty percent of cases originated from Santiago and 60% from public hospitals.
      Eighty three percent of analyzed medical records were complete and in 70% the
      number of laboratory tests requested was adequate. The most frequent conditions
      that motivated lawsuits were acute fetal distress and puerperal sepsis in
      Obstetrics and Gynecology, acute abdomen and intra-operatory cardiac arrests in
      Surgery and sepsis in Internal Medicine. The risk of an unfavorable consequence
      that may lead to a lawsuit is present in every clinical condition, even in
      seemingly simple situations.

PMID- 8272610
TI  - [Surgery of acute mitral valve insufficiency].
AB  - Between January 1980 and December 1990, 16 patients with acute mitral
      insufficiency were operated on an emergency basis at our institution. They
      represented 1.8% of all mitral surgical cases. All of them were in acute
      pulmonary edema and 7 in cardiogenic shock. The etiology was ischemic in 6,
      degenerative in 4, infectious in 3, degenerative and infectious in 2 and
      traumatic in 1. The pathologic mechanism was chordal rupture in 8 patients (5
      anterior) and papillary muscle rupture in the other 8 (5 posterior). A mitral
      valve replacement was performed in all cases. Two patients died and 7 had
      morbidity in the postoperative period. One patient died 6 months after surgery of
      congestive heart failure. Ten patients are in NYHA functional class I at a mean
      follow-up of 48.1 months. Acute mitral insufficiency has different etiologies and
      pathologic mechanisms. In spite of the severe clinical condition of these
      patients, mitral valve replacement has good immediate and long-term results.

PMID- 8272611
TI  - [Extracorporeal lithotripsy by shock waves: results in 185 patients].
AB  - Extracorporeal shock wave lithotripsy has become the treatment of choice of
      nephrolithiasis with surgical indication. Our unit is managing urinary tract
      stones using the Sonolith 3000 lithotritor since April 1991. The procedure is
      performed in ambulatory patients and requires analgesia and mild sedation. We
      report the experience in the treatment of the first 185 patients. In 87% of them,
      the stones disappeared completely, 8.7% of patients were left with residual
      fragments without indication of further treatments and in 4.3% the procedure
      failed. There was no mortality. In 13 occasions, obstructive complications at the
      distal ureter were produced by the stone fragments that required ureteroscopy in
      only three patients and 11 patients had severe renal colic. We conclude that this
      procedure is safe and effective in the treatment of urinary tract stones.

PMID- 8272612
TI  - [Deltamethrin-piperonyl butoxide (Launol) in the treatment of scabies. Clinical
      experience with 33 patients].
AB  - Deltametrin is an effective but not well tolerated treatment of scabies. The
      association with piperonil-butoxide allows shorter treatment periods, thereby
      reducing its adverse effects. We used this combination in the treatment of 33
      patients with active scabies. Two treatment modalities were used with four or
      five applications, during 7 or 8 days respectively and patients were assessed two
      weeks later. Treatment was effective and well tolerated in 32 of the 33 patients
      and no differences were observed between the two modalities. It is concluded that
      this is an effective therapy for scabies.

PMID- 8272613
TI  - [Post sinusoidal obstruction of the hepatic venous flow associated with
      antiphospholipid syndrome in 3 cases].
AB  - Three cases of post-sinusoidal hepatic blood flow obstruction as the main feature
      of antiphospholipid syndrome are reported. Clinically, these patients developed
      jaundice, malaise, ascites and hepatomegaly. Ultrasonography-Doppler and hepatic
      venography showed small hepatic vein disease in two and partial occlusion in the
      suprahepatic segment of inferior vena cava in the remaining patient. In all,
      anticardiolipin antibodies were positive and activated partial thromboplastin
      time was prolonged. This experience emphasizes that in patients with post
      sinusoidal portal hypertension, a systematic search for antiphospholipid syndrome
      must be carried out.

PMID- 8272614
TI  - [Secondary amenorrhea and LH hypersecretion. An unusual report of a granulosa
      cell ovarian tumor].
AB  - Granulosa cell ovarian tumors are infrequent. Since they originate from the
      gonadal stroma, they retain a high secretory potential and some of their clinical
      manifestations may be secondary to the production of sexual steroids. A 36 year
      old woman with an ovarian tumor presenting as a secondary amenorrhea is reported.
      This patient had a positive progesterone test and her hormonal profile showed a
      maintained LH hypersecretion (> 75 mUl/ml) which, joined to the presence of a
      hypophyseal microadenoma lead to suspect the presence of a gonadotrophin
      secreting tumor. The absence of LH response to TRH and its adequate suppression
      using oral contraceptives discarded this diagnosis. The histopathology of the
      excised ovarian tumor demonstrated that it is was a granulosa cell tumor. The
      physiopathological explanation of the case is based on the maintained levels of
      estrogens produced by the tumor that, through a positive feed-back mechanism
      similar to that of the polycystic ovary syndrome, produced a tonic LH elevation
      and GnRH hyper response. After the tumor excision, ovulatory cycles resumed and
      the patient became pregnant, facts that confirm the postulated hypothesis.

PMID- 8272615
TI  - [Vascular compression syndrome of the duodenum. Report of 2 cases].
AB  - Two young female patients with the syndrome of vascular compression of the
      duodenum are reported. Both patients presented with a history of vomiting and
      weight loss. Barium examination of the gastrointestinal tract showed in both
      cases, marked stomach distention and obstruction of the third portion of the
      duodenum. In one patient, abdominal CT scan discarded other causes of extrinsic
      compression. Both patients were operated. The simpler and safer surgical
      procedure is the section of the Treitz ligament and duodenal liberation, which
      can be used in the majority of patients.

PMID- 8272616
TI  - [Extracorporeal lithotripsy in percutaneous urinary lithiasis].

PMID- 8272617
TI  - [Medical liability].

PMID- 8272618
TI  - [Depression and climacteric. Clinical and neuroendocrinological aspects].
AB  - The clinical and neuroendocrine evidences that link depression with menopause are
      reviewed. Climacteric is associated with depressive symptoms, but these do not
      form a definite depressive entity. Depression would be due to the disregulation
      of brain noradrenergic and serotoninergic systems. Gonadal steroids modify the
      neurotransmission of these systems and may influence the mood regulations.
      Depression appearing in the climacteric period must be treated with
      antidepressants. The depressive symptoms associated to estrogen deficit may
      improve with hormonal substitution.

PMID- 8272619
TI  - [Ursodeoxycholic acid in the treatment of cholestatic liver diseases].
AB  - Ursodeoxycholic acid (UDCA) is a hydrophilic biliary acid that has been used in
      the medical therapy of cholelithiasis. In the last decade, its use in the
      treatment of some liver diseases renewed the interest on its hepato-protective
      properties. Controlled trials have demonstrated that UDCA has symptomatic and
      laboratory beneficial effects in primary biliary cirrhosis and sclerosing
      cholangitis. However its effects on the long-term and patients survival have not
      been determined. Uncontrolled trials on the effects of UDCA on a series of
      cholestatic liver diseases (cystic fibrosis, chronic hepatitis, cholestasis of
      pregnancy, etc) have communicated promising results that require confirmation
      with methodologically rigorous studies. The research in this area has
      significantly stimulated the study of the mechanisms of cellular injury
      associated to cholestatic phenomena and its prevention or attenuation with UDCA.
      The present review analyzes the most outstanding aspects of UDCA mechanisms of
      action, pharmacology and clinical efficacy in the treatment of liver diseases.

PMID- 8272620
TI  - [Blood transfusions in Jehovah's witnesses].
AB  - Jehovah Witnesses cite religious motives to refuse transfusions of whole blood or
      its components for themselves and their children, even when life is endangered.
      An ethical analysis of decision making in health problems is made, giving
      priority to the alternatives chosen by the patient. One of the elements that
      turns a therapeutic procedure into extraordinary is the moral impossibility of
      its use, originated in a subjective cause. The right to act with freedom in
      religious matters must also be considered. It is concluded that the denial of a
      Jehovah Witness to be transfused must be respected. However, in the case of
      children, the physicians should disregard the parents rejection.

PMID- 8272621
TI  - [Physician's role in the society].
AB  - The role that a physician must accomplish in the community must satisfy the hopes
      and requirements of the people. Actually, the physicians have a sporadic and
      occasional contact with their patients and preventive care is difficult. Medical
      care is dehumanized, impersonal and expensive. At the primary care level there
      are many patients and few physicians. This "system" is historically new since,
      formerly, physicians were general practitioners that provided an intuitive and
      comprehensive care. Medical education is performed with hospitalized patients;
      when these students start to practice their profession, they realize that,
      surprisingly, these subjects walk, talk and do not wear a pyjamas. The actual
      situation of medical profession is not the desired one and the community expects
      other roles for physicians. Medical education must be redesigned.

PMID- 8272622
TI  - [Identical monozygotic triplets: the 1st case in Chile].

PMID- 8272623
TI  - [Laparoscopic cholecystectomy makes the histopathological study of the
      gallbladder mucosa difficult].

PMID- 8272624
TI  - [Thallium-201 in the non-invasive evaluation of coronary cardiopathy].

PMID- 8272625
TI  - [Risk behavior in adolescent students in Santiago de Chile].
AB  - Aiming to measure the prevalence of risky behaviors, familial disturbances and
      their interrelations, a probabilistic sample of 1904 teenagers (aged 15.5 +/- 1.8
      years, 42% male) was surveyed using and anonymous and self applied questionnaire.
      Fifty two percent of the sample smoked, 54% consumed alcohol, 12.5% marihuana,
      3.2% amphetamines, 2.3% cocaine, 0.8% inhalants and 5.3% other drugs. Thirty two
      percent smoked frequently (monthly, weekly or daily); frequent alcohol,
      marihuana, amphetamines, cocaine and other drug consumption was found in 15.5, 5,
      1.4, 0.4 and 1.4% of the sample. Substance abuse, except cigarette smoking was
      more prevalent among males. Substance abuse was more frequent among people over
      15 years old. As to unsociable behaviors, 24% of teenagers referred vandalism in
      the last 24 months, 44% individual aggressions and 14% robbery. Twenty nine
      percent had school absenteeism. Parental separation, psychiatric treatments and
      treatments for alcoholism were present in 22, 6 and 4 percent of teenagers. Risky
      behaviors were significantly more frequent among offspring whose parents had any
      of these problems.

PMID- 8272626
TI  - [Pathogenic potential of vibrio cholerae 01 isolated from the Mapocho river and
      Aguada ditch].
AB  - The pathogenic potential of 20 strains of Vibrio Cholerae 01 isolated from the
      Mapocho river and Aguada ditch in Santiago, Chile was studied using a rabbit
      intestinal loop biological model. The presence of cholera toxin (CT) was
      previously found by the detection of CT gene, ELISA and passive reserve
      agglutination in only one of these strains. After 24 h of intestinal loop
      inoculation, the 20 strains showed enterotoxic activity. In four of these strains
      the secretory reaction was particularly intense. In these same four strains, the
      presence of cholera toxin was detected after the passage through the animal
      model. Thus, the number of cholera toxin producing strains increased after the
      inoculation in intestinal loops. These results suggest that the enterotoxic
      activity of strains that do not produce CT is given by the new cholera toxin
      (NCT). It is concluded that most of the strains of Vibrio Cholerae isolated from
      Mapocho river and its affluents are producers of NCT toxin, that some strains
      recover the capacity to produce CT after colonization of intestinal loops of
      living organisms and that the additive effects of CT and NCT may explain the
      intense enterotoxic activity of the strains that produce CT.

PMID- 8272627
TI  - [Lactulose fermentation and lactose absorption in Chilean patients with liver
      cirrhosis: importance for hepatic encephalopathy therapy].
AB  - BACKGROUND: Non-absorbable carbohydrates are widely used in the therapy of
      hepatic encephalopathy. It has been argued that their effects depend on
      intestinal fermentation. In some geographic areas other than Chile up to 27% of
      healthy inhabitants are not able to increase breath hydrogen after a lactulose
      load, a parameter of intestinal fermentation of carbohydrate. Lactose has been
      proposed as an alternative to non-absorbable disaccharides in patients with
      lactase deficiency. AIM: To investigate intestinal fermentation of lactulose and
      lactose malabsorption in Chilean patients with liver cirrhosis. PATIENTS AND
      METHODS: 22 healthy controls and 52 patients with liver cirrhosis (16 with
      hepatic encephalopathy) were prospectively studied by means of lactulose or
      lactose hydrogen breath tests and lactose tolerance test. MAIN RESULTS: In the
      control group, 19% were non-hydrogen excretors after lactulose, meanwhile a
      significant rise in breath hydrogen concentration was observed in all cirrhotic
      patients (p < 0.01). Lactose tolerance test was indicative of lactase persistance
      in 37% of cirrhotics and in 43% of controls (NS). Finally, 41% of cirrhotics and
      50% of controls had a normal lactose hydrogen breath test (NS). These results
      were not significantly modified by the presence of hepatic encephalopathy.
      CONCLUSION: Our data suggest that a lack in bacterial fermentation is not a cause
      of lactulose therapy failure in Chilean patients with hepatic encephalopathy.
      Lactose might be an inappropriate substitute to lactulose treating a significant
      proportion of patients with this condition in our country.

PMID- 8272628
TI  - [Genetic composition of Chilean population: the Pehuenches from Trapa-Trapa].
AB  - This study describes the genetic composition of Pehuenche indians from Trapa
      Trapa. The admixture analysis revealed that this group has conserved most of its
      pre-Columbian gene pool and therefore, is representative of the indians that
      lived in Southern Chile before the Spanish conquest. A relatively high frequency
      of a esterase D variant seems to indicate that this is a Chilean aboriginal
      population marker. The Chilean Pehuenches are genetically similar to their
      Argentinean relatives, which is not surprising since this last group crossed the
      Andes Mountains in historic times.

PMID- 8272629
TI  - [Bacteriuria in patients with primary biliary cirrhosis].
AB  - BACKGROUND: Controversies exist about the association between significant
      bacteriuria and primary biliary cirrhosis. There is evidence suggesting that
      infections by Gram negative bacteria may be implicated in the pathogenesis of
      this liver disease. AIM: To compare the incidence of bacteriuria in patients with
      primary biliary cirrhosis and those with autoimmune chronic hepatitis. PATIENTS
      AND METHODS: Twenty women with primary biliary cirrhosis and twenty three female
      patients with autoimmune chronic hepatitis were prospectively studied by routine
      bacteriological cultures of midstream urine specimens. Samples were obtained at
      three months intervals or when patients complained of symptoms suggesting urinary
      tract infection. Significant bacteriuria was defined as the growth of > 10(5)
      organisms/ml in pure culture. RESULTS: During 8 +/- 1 months of follow up. 60
      urine samples from patients with primary biliary cirrhosis and 73 from autoimmune
      hepatitis cases were tested. Twenty one samples of patients with primary biliary
      cirrhosis (35%) were positive for significant bacteriuria compared with 7 from
      women with autoimmune hepatitis (9%); p < 0.01. In the follow up, ten patients
      with primary biliary cirrhosis (50%) and six with autoimmune hepatitis (26%)
      developed at least one episode of significant bacteriuria. CONCLUSION: These
      results suggest that female patients with primary biliary cirrhosis are in higher
      risk of significant bacteriuria than women with autoimmune hepatitis. Prospective
      studies evaluating the effects of long-term antibiotic therapy on cholestasis
      parameters in primary biliary cirrhosis are deserved.

PMID- 8272630
TI  - [Hepatitis B virus vaccine: early and late response in Chileans with high risk of
      infection].
AB  - BACKGROUND: Hepatitis B vaccine has demonstrated to be very effective and safe
      preventing hepatitis B virus infection. Long term protection induced by hepatitis
      B vaccination depends on the initial immune response and the declining rate of
      anti-HBs titers. AIM. To investigate early and late response to hepatitis B
      vaccine in a sample of high risk Chilean population. MATERIAL AND METHODS: Thirty
      one subjects (20 relatives of hepatitis B chronic carriers, 10 health service
      workers and one HIV seropositive) were vaccinated with a plasma derivated
      hepatitis B vaccine. Early and late response were estimated by anti-HBs titers.
      RESULTS: Twenty eight subjects (90%) produced protective titers of anti-HBs after
      2 months from the third dose of vaccine (early response), and they remained at
      these levels in 75% of vaccinated individuals after three years (late response).
      All the subjects without protective titers after the three year follow up had
      produced anti-HBs levels lower than 300 UI at the early response. Hepatitis B
      vaccination was not associated with significant side effects. CONCLUSIONS: This
      experience confirms that hepatitis B vaccine is safe and effective inducing
      immunity in high risk subjects. Our data suggest that the early response to
      hepatitis B vaccine is able to identify those subjects requiring closer
      surveillance for boosters.

PMID- 8272631
TI  - [Transesophageal echocardiography: experience with the first 500 consecutive
      cases].
AB  - The results of all the transesophageal echocardiographies (TEE) performed between
      June 1989 and February 1992 are analyzed. Five hundred patients (240 male) with a
      median age of 57 years (range 13-88) were examined; during the same period, 5180
      transthoracic echocardiographies were performed. TEE were requested for the
      following reasons: valvular prosthesis disfunction in 132 patients, rheumatic
      valvulopathy in 103, search for embolic origins in 97, study of congenital
      cardiopathies in 48, bacterial endocarditis in 35, aortic dissection in 25 and
      miscellaneous in 78. Among congenital cardiopathies there were 29 cases of
      interauricular communication and among miscellaneous cases, 9 patients with
      cardiac tumors. No major complications occurred. The imaging quality of this
      technique renders it specially important in the study of prosthesis disfunction,
      mitral valve analysis before valvuloplasty, detection of cardiac origins of
      emboli and infective endocarditis complications and anatomical and dynamic
      analysis of aortic dissection. It is concluded that TEE is a safe technique that
      provides high quality images and visualizes segments of the heart and great
      vessels formerly inaccessible with transthoracic echocardiography. It has
      enlarged the diagnostic capacity of echocardiography and improved the support of
      therapeutic decisions.

PMID- 8272632
TI  - [Efficacy and secondary effects of chronic treatment with amiodarone].
AB  - Long-term therapy with amiodarone has been associated with a high incidence of
      adverse side effects, that precludes its indication for common cardiac
      arrhythmias. We have prospectively studied 218 patients (pts), aged 32-87 years,
      under chronic amiodarone therapy that were followed for 2 years and evaluated for
      efficacy and adverse side effects. Previous amiodarone treatment ranged from 1 to
      135 months. Cardiac arrhythmias were paroxysmal AF (PAF) in 120 pts, sustained VT
      (SVT) in 36 pts, paroxysmal supraventricular tachycardia (PSVT) in 21 pts,
      unsustained VT (UVT) in 18 pts and miscellaneous in 23 pts. Amiodarone doses
      ranged from 500 to 4200 mg per week. Amiodarone was effective in 65% of all
      patients. No difference was observed between efficacy and type of arrhythmia.
      Dermatologic toxicity was found in 36%, neurologic toxicity in 23%, thyroid
      toxicity in 13.4% and pulmonary fibrosis en 2.5% of pts. Amiodarone was
      discontinued routinely when pulmonary toxicity was present. We conclude that
      amiodarone therapy is effective in a wide spectrum of arrhythmias. Although drug
      therapy was associated with a high incidence of adverse side effects, these did
      not preclude continuation of treatment.

PMID- 8272633
TI  - [HLA A, B, C and DR antigens in a urban population from Santiago of Chile].
AB  - HLA antigens vary in different ethnical groups and in Chile there are no reports
      on the frequency of these antigens in a normal representative population. The few
      existing studies are of indigenous populations and control groups, without
      including HLA-DR antigens. Therefore, the aim of this study was to study the
      frequency of HLA A, B and C antigens in 349 individuals and HLA-DR in 257, using
      the microlymphocytotoxicity method, and compared the results with those on normal
      caucasian populations (Europe and USA). Significant differences were found for 7
      antigens of group A, 10 of group B, 4 of group C and 6 of group DR. The observed
      difference allow us to conclude that the population from Santiago has a distinct
      HLA antigen distribution. This fact must be bore in mind future studies in
      genetics, paternity or autoimmune diseases.

PMID- 8272634
TI  - [APS-2: comparative study on populations of critical patients in Chile, United
      States and New Zealand].
AB  - Between 1988 and 1991, the Acute Physiologic Score (APS-2) was applied to 1000
      critically ill patients admitted to an intensive care unit of a general hospital
      in Chile. Its predictive capacity was assessed and compared with two series from
      United States and New Zealand. The mean admission APS-2 in Chilean patients was
      12.8 and there was a progressive increase in mortality with elevating scores; no
      patient with an APS-2 over 30 survived. Admission APS-2 scores in USA and New
      Zealand were 10.7 and 14.2. Overall mortality in Chilean patients was 28%,
      compared with 12% in USA and 15% in New Zealand. Within different score ranges,
      mortality was higher in Chilean patients than those from USA or New Zealand. It
      is concluded that the assessment of admission APS-2 score underlying diagnosis,
      physiologic age and previous health status of a patient may help to predict the
      success of intensive care.

PMID- 8272635
TI  - [Changes in coagulation in patients with sepsis].
AB  - Aiming to know the coagulation disorders that occur in patients with sepsis, a
      retrospective study of 75 such patients hospitalized in an Intensive Care Unit
      was performed. The coagulation profile requested by the attending physician, that
      included platelet count, prothrombin time, partial thromboplastin time, thrombin
      time, protamine sulphate test, fibrinogen and euglobin lysis time, was analyzed.
      Fourteen patients that were receiving prophylactic subcutaneous heparin were
      excluded from further analysis. Of the 61 remaining patients, 23 had hemorrhagic
      manifestations and 94.4% of these had multiple alterations in coagulation
      parameters. Eighty one percent of patients had abnormal prothrombin time and 73%
      thrombocytopenia. Isolated alterations were infrequent and consisted in
      thrombocytopenia (3.7%) and fibrinogen elevation (1.9%). Fifty two percent of
      patients had shock and they had significantly lower platelet counts and higher
      prothrombin and thrombin times than patients without hemodynamic disturbances.
      Global mortality was 63.9%. No relation between coagulation disturbances and
      mortality was observed. Likewise, no differences in mortality between patients
      with or without shock was observed. It is concluded that coagulation is
      frequently disturbed in patients with sepsis, even without clinical hemorrhagic
      symptoms, that these abnormalities are more marked in patients in shock and that
      53% of these are consistent with intravascular coagulation.

PMID- 8272636
TI  - [Population, genes and diseases: searching for the roots].

PMID- 8272637
TI  - [Child abuse].

PMID- 8272638
TI  - [New treatments for old arrhythmias].

PMID- 8272639
TI  - [Pregnancy and portal hypertension].
AB  - The course of pregnancy in three patients with portal hypertension is described.
      The cause of portal hypertension was cirrhosis in one and portal vein obstruction
      in two (one of these had previous shunt surgery). The patient with cirrhosis had
      an episode of encephalopathy at week 27, the rest of the patients had an
      uneventful pregnancy. All three had preterm vaginal deliveries at week 33, 31 and
      37 of pregnancy. The clinical features of pregnancy in women with portal
      hypertension was reviewed in the literature. There is agreement that the risk of
      preterm delivery increases and pregnancy does not influence maternal prognosis.
      Vaginal delivery can be anticipated in most women and cesarean section is
      reserved for obstetric indications. Pregnancy in these women should be managed in
      tertiary care centers with close collaboration between perinatologists,
      internists and surgeons.

PMID- 8272640
TI  - [Multiple splenic abscesses. Report of 2 cases].
AB  - Splenic abscesses are infrequent and usually associated to sepsis and
      immunodepression. The diagnosis is commonly made in the necropsy. We report two
      cases of multiple splenic abscesses in type II diabetic patients that were
      diagnosed by ultrasound. Both patients were successfully managed with surgery
      (drainage of left subphrenic space in one and splenectomy in the other) and
      antimicrobial agents.

PMID- 8272641
TI  - [Premenstrual syndrome: a neglected public health problem].
AB  - Premenstrual syndrome (PMS) is a clinical entity of great importance in medical
      practice, due to its high prevalence and its symptomatic polymorphism. In 25 to
      35% of women it is a worrisome problem, that requires specialized consultation
      and in 5 to 10% it becomes grave, due to the extension or seriousness of
      symptoms. According to our personal understanding, this is a toxic-inflammatory
      process with multisystemic involvement that erroneously leads women to consult
      diverse specialists such as neurologists, cardiologists, psychiatrists etc. Each
      of these professionals will prescribe symptomatic treatments with uncertain or
      negative results. PMS and its toxic-inflammatory components apparently acquires a
      progressive course and the lack of causal treatment may compromise women's
      fertility and lead to premature and mutilant surgical practices (hysterectomy).

PMID- 8272642
TI  - [Physical punishment in children: opinions and behaviors of adults].
AB  - Five hundred twenty seven parents and tutors from three schools of Santiago were
      surveyed, using anonymous inquiry, to know behaviors and opinions towards child
      abuse. Sixty three percent of the sample judged physical punishment useless as an
      educational tool. However, 75% tacitly admitted to hit children, when they were
      asked a question about the ways they used to punish them. This question was
      answered by a significantly higher proportion of women. The principal reasons to
      use physical punishments were defying attitudes, lack of study and running away
      from home. The principal ways of physical punishment were hand blows (49%),
      lashes with belts (13%) and shaking (19%). The principal punitive restrictions
      were restrains from going out of home (70%) or watching television (46%) and not
      talking to children (14%). Sixty six percent of parents reminded physical
      punishments during their childhood. This background was associated with a higher
      frequency of actual battering. It is concluded that there is incoherence between
      real behavior and opinions towards child battering among parents and that the
      magnitude of this problem precludes its short term eradication.

PMID- 8272643
TI  - [Life style: instrument in health promotion programs].
AB  - Non communicable diseases are increasing in third world countries, including
      Chile. Life style is one of the principal factors influencing this increase.
      Therefore programs and health strategies to modify the population life styles are
      needed. The programs developed to change life styles depend on the medical
      sociocultural scenery and the concept becomes outstanding when disease prevention
      is replaced by health promotion. The requirements for the application of the
      concept of life style in health promotion plans and fostering of healthy life
      styles are: 1) Training in behavioral epidemiology. 2) Election of a
      biopsychosocial concept of life style. 3) Identify the predominant scenery and
      target population. 4) Choose the appropriate educational methodologies to change
      behaviors. 5) Formalize strategies according to the boundaries where the program
      is applied. 6) Specify the qualifying requisites of the change agents, health
      promoters and program operators.

PMID- 8272644
TI  - [Fiftieth anniversary of classical genetics of professor Noe (1943-1993)].
AB  - Fifty years ago, the author was a student of Dr Juan Noe's general biology
      course. Dr Noe, an italian physician and biologist, was the most outstanding
      european teacher in Chile during the first half of twentieth century (1912-1947)
      and was the founder of the "Instituto de Biologia de la Universidad de Chile". In
      1943 Dr Noe taught to the author the classical genetics of that age that included
      basic concepts of mendelian theory, evolution, comparative anatomy, cytogenetics,
      eugenics and normal and pathological inheritance. He also undertook controversial
      problems of those times such as eugenics, racism, humanism and the ambiguity
      about "inherited defects" associated to syphilis, alcoholism and tuberculosis.
      The author received a firm education on the history of biological sciences,
      mendelism, evolution and genetic etiology of classical hereditary diseases such
      as hemophilia, daltonism, Huntington chorea and muscular dystrophy. Furthermore,
      Noe made mention of the hereditary etiology of cancer in animals and human
      leukemias and of the concept of polygenic diseases as a consequence inheritance
      environment interactions. The author concludes emphasizing the importance of
      basic and clinical education in the teaching of medical genetics.

PMID- 8272645
TI  - Modern medical research ethics.

PMID- 8272646
TI  - The selection of appropriate health education topics for publication in the
      press.
AB  - OBJECTIVE: To compare the perceptions of patients, doctors, and journalists
      concerning the priority of health education topics in the media. DESIGN: A cross
      sectional Knowledge, Attitude, and Practice (K.A.P.) study. A self-administered
      questionnaire was used during 2 weeks in September 1990; it included questions on
      sociodemographic characteristics and on each group's perceived opinion of
      priority health topics for discussion in the media. SETTING: Two university
      hospitals and six newspapers offices in Riyadh Saudi Arabia. PARTICIPANTS: 300
      randomly selected outpatients aged 12 years and over, and 77 doctors. 31
      journalists from six local newspapers also participated. MAIN OUTCOME MEASURE:
      The ratio of respondents in the three study groups who believed there was a need
      for health education in 22 topics. RESULTS: For most of these topics,
      statistically significant differences were found between the perceptions of the
      three groups. Doctors put more emphasis on preventive issues, while patients
      perceived new therapeutic and diagnostic methods as important more commonly than
      the other two groups. CONCLUSION: A team consisting of doctors, journalists, and
      patients should be formed to select health education topics in the media.
      Priority should be given to topic preferences shared by both doctors and the
      public.

PMID- 8272647
TI  - Ethnicity as a risk factor for consultations in primary health care and out
      patient care.
AB  - OBJECTIVE: To determine the influence of ethnicity, defined as foreign-born
      people, on consultation rates, admissions and prescriptions in out-patient care
      and primary health care. DESIGN: Prospective study of attenders at four different
      caregivers during seven consecutive weeks in 1988. Age-and sex-standardized
      relative risks and odds ratios with 95% confidence interval were calculated.
      SETTING: A suburban area in Lund, a city located in the south of Sweden, with 28%
      foreign-born people. SUBJECTS: This population (N = 5085) made 1,348
      consultations. MAIN OUTCOME MEASURES: Ethnic group and consultation rates of the
      local primary health care centre, the emergency department, hospital out-patient
      department, and private care, admissions to specialist care, prescriptions, and
      certified sick leave. RESULTS: Swedes made fewer age-and sex-standardized visits
      to the emergency department (RR = 0.69(0.48-0.99)) while the foreign-born people
      showed an opposite non-significant trend (RR = 1.37(0.95-1.99)). Latin Americans
      (RR = 1.60(1.02-2.51)) visited the local Primary Health Care centre in the
      residential area more than expected, while people born in Asia and Africa
      consulted the Primary Health Care centre less than expected (RR = 0.44(0.28
      0.69)). There were no differences between Swedes and foreign-born people in being
      put on the sick-list, but foreign-born people were given significantly fewer
      prescriptions (RR = 0.07(0.03-0.19)) than Swedes. Foreign-born people, Latin
      Americans, and non-Swedish Scandinavians were referred significantly more often
      to hospital than other groups. CONCLUSIONS: There were important differences in
      consultations between Swedes and foreign-born people. It seems important to study
      these differences further to find out if they were due to morbidity or cultural
      differences in order to be able to meet the demands and needs of different ethnic
      groups.

PMID- 8272648
TI  - Risk factors for acute myocardial infarction among men in the subarctic area.
AB  - OBJECTIVE: To describe and quantify the main risk factors for acute myocardial
      infarction (AMI) among males in the subarctic region of Sweden. DESIGN: Case
      control study comprising a questionnaire and a clinical examination. SETTING:
      Kiruna, a town about 100 miles north of the Arctic Circle with a very high
      mortality from ischaemic heart disease. SUBJECTS: 219 patients 35 to 64 years of
      age admitted to Kiruna District Hospital with a first myocardial infarction
      between 1973 and 1985, and 438 age-matched controls. RESULTS: The main risk
      factors for the whole group were hypertension (odds ratio [OR] 3.5), family
      history of AMI (OR 2.2), diabetes mellitus (OR 2.2), and smoking (OR 1.7). The
      distribution and strength of the risk factors differed between Kiruna-born and
      migrants into the community. CONCLUSION: Apart from the traditional risk factors,
      environmental and psycho-social factors and population dynamics must be taken
      into account when assessing the risk for a man in Kiruna of developing a
      myocardial infarction.

PMID- 8272649
TI  - Drug interactions in primary health care. A retrospective database study and its
      implications for the design of a computerized decision support system.
AB  - OBJECTIVE: To investigate the occurrence of potential drug interactions in
      primary health care from the perspective of the prescribing general practitioner.
      DESIGN: Retrospective database study of computer-based patient records with a
      query language. All drug prescriptions during a four year period were compared
      with concurrent or overlapping prescriptions for the same patient and these drug
      pairs were compared with a database of drug interactions from the Swedish drug
      catalogue. SETTING: One health centre in Sweden with six general practitioners
      and two doctors on vocational training. PARTICIPANTS: All patients who had
      visited a doctor at the health centre between 1 November 1986 and 31 October
      1990. MAIN OUTCOME MEASURES: The rate of potential interactions in relation to
      all drug prescriptions and the incidence rate of potential interactions for
      patients at risk (those receiving two or more drugs). RESULTS: Approximately
      55,000 drug prescriptions were analysed for potential drug interactions. A total
      of 1,074 cases of potential drug interactions were found, which corresponds to a
      rate of 1.9% of all drug prescriptions. The incidence rate of potential
      interactions was 12% for all patients at risk (those receiving two or more drugs)
      and 22% for elderly (> = 65 years of age) patients at risk. Major interactions
      were investigated concerning the extent to which the prescribing doctors were
      aware of the potential interactions. CONCLUSION: Potential drug interactions
      occur at a high rate in general practice, in particular for elderly patients.
      Properly designed computer-based decision-support might increase the prescribing
      doctor's awareness of clinically significant interactions and improve the quality
      of drug treatment.

PMID- 8272650
TI  - Swedish general practitioners' practice behaviour in hypertension care.
AB  - OBJECTIVE: To examine care organization and practice behaviour in hypertension
      care among Swedish general practitioners. DESIGN: A postal questionnaire followed
      by a structured interview, in a two-step study design. SETTING: Uppsala-Orebro
      region in mid-Sweden (population 1.9 mill.) PARTICIPANTS: General practitioners
      employed by counties, according to a register maintained by the Swedish Medical
      Association (N = 489). MAIN OUTCOME MEASURE: Practice behaviour score compared
      with a gold standard. RESULTS: 392 general practitioners returned the
      questionnaire, and the interview was accomplished with 222 of 232 who agreed to
      participate. Non-responder studies were carried out in both steps. Every fifth GP
      had access to a special hypertension clinic at their health centre, and 29% had
      specially trained nurses for hypertension care. 31% reported use of written
      guidelines. 47% declared they accepted higher BP-levels than recommended,
      although 78% agreed with official guidelines. The mean practice behaviour score
      was 8,77 (range 5-12, maximum score 12). CONCLUSION: Although a majority of GPs
      agree with official guidelines, there is a considerable variation in care
      organization and practice behaviour in hypertension care.

PMID- 8272651
TI  - One hundred and fifty men with urinary incontinence. III. Psychosocial
      consequences.
AB  - OBJECTIVE: To investigate the psychosocial impact of urinary incontinence among
      men. DESIGN: Telephone interviews with men who had give their written consent to
      participate. SUBJECTS: 150 men were available for interviews out of 571 who had
      asked for information about urinary incontinence and free samples of pads by
      post. MAIN OUTCOME MEASURES: Questionnaire which mapped demographic data,
      occupational status, medical history, medication, and toilet habits. Duration,
      frequency, and amount of leakage were registered, and the incontinence was
      classified according to a symptom questionnaire. Consultations and other sources
      of help were also registered, together with use of control methods, emotional,
      practical, and social consequences. RESULTS: Twenty-four per cent stated that
      their incontinence was a negligible problem. Generally, increasing severity of
      the incontinence caused more mental distress and social restrictions. Younger men
      were more handicapped than the older men. Practical inconveniences and social
      restrictions increased with longer duration of the incontinence. A multiple
      regression analysis, using a severity index, duration, type, and age as
      explanatory variables for the degree of mental distress, practical
      inconveniences, and social restrictions could explain 7%, 12%, and 25% of the
      variation in these groups of consequences, respectively. CONCLUSION: Urinary
      incontinence is associated with negative psychosocial effects, the impact
      increasing with the severity of the incontinence and decreasing with age of the
      incontinent men.

PMID- 8272652
TI  - Upper airway infections in preschool children--frequency and risk factors.
AB  - OBJECTIVE: To estimate the frequency of upper respiratory tract infections (URTI)
      over a three month period and possible risk factors in the social surroundings,
      daily routines and health history. DESIGN: A retrospective epidemiological survey
      by means of questionnaires. SETTING: Gardabaer, a small town, ten km south of
      Reykjavik, Iceland. PARTICIPANTS: All children in Gardabaer, six months to six
      years old (n = 555). MAIN OUTCOME MEASURE: Number of URTI and possible risk
      factors. RESULTS: The response rate was 81.8%. The most common infections were
      common cold (n = 345), acute otitis media (n = 82), sore throat (n = 75), and
      bronchitis (n = 13). The mean frequency of URTI during the previous three months
      was 2.2 in boys and 1.7 in girls (p < 0.01). Log-linear regression analysis
      showed that the predicted number of URTI was 1.9 higher if the child was
      attending day care, and that the number of URTI increased by 1.015 with each
      month until the age of 24 months, but decreased after that by 0.985. CONCLUSIONS:
      The major factors which affect the frequency of URTI are: age, sex, family
      history of frequent URTI, asthma, allergy, and the form of day care. Measures to
      reduce URTI could involve prospective intervention studies on the form of day
      care.

PMID- 8272653
TI  - Acute illnesses in children. A description and analysis of the cumulative
      incidence proportion.
AB  - OBJECTIVES: To describe parent-reported morbidity in relation to the psycho
      social conditions of the families and to characterize families whose children are
      frequently ill. DESIGN: The parent-reported morbidity in a two-month prospective
      period, and the psychosocial conditions of the families were registered by means
      of a questionnaire. The conditioned probability of parents' reporting an episode
      of illness was estimated by means of logistic regression analysis, taking the
      psycho-social conditions into consideration. SETTING: 18,949 families with at
      least one child under the age of 8 years, resident in the County of Ringkjobing
      in western Denmark at 1 March 1988. SUBJECTS: An age-stratified random sample of
      1982 families was entered in the study. 1588 (82%) families returned the
      questionnaire. RESULTS: The parents reported considerable morbidity in their
      children. The cumulative incidence proportion (CIP) for the period was 48%. The
      multivariate analysis of the parent-reported morbidity led to the following main
      results: 1) the morbidity was greatest for children aged 6 to 18 months, after
      which it decreased with age, 2) there was interaction between the care conditions
      and the child's age--CIP for children up to two years was largest for the
      children who were cared for in daycare, while the CIP for the older children was
      largest for the children who were cared for at home, 3) if the parents reported
      that the child's siblings suffered from chronic or frequently recurring
      morbidity, the child's morbidity rate was significantly increased, 4) mothers
      with higher education reported more morbidity in their children than mothers
      without this education, and 5) parents with a high perception of the general
      health threat ("worried" parents) reported more morbidity than did parents with a
      low perception. CONCLUSIONS: The results made it possible to characterize
      families whose children were frequently reported ill.

PMID- 8272654
TI  - Current health as a general health indicator. I: Evaluation of scaling
      properties.
AB  - OBJECTIVE: To examine to which extent 9 items pertaining to health perception
      fulfil the Likert criteria for adding the scores for each item to make up a
      Current Health scale. The term "scaling" denotes the process of constructing a
      scale from questionnaire items. DESIGN: Examination of convergent and
      discriminant validity of items, groupings of items, item variance, and
      information content of each item. SUBJECTS: 2,263 male and female heads of
      households who participated in The Danish Health Study 1982-83. The survey used
      items pertaining to health status from Rand's Health Insurance Study. RESULTS:
      The Likert criteria for constructing a scale of the nine items are fulfilled
      except for one item. The lack of fulfillment for this item can eventually be
      attributed to the translation.

PMID- 8272655
TI  - A clinical follow up of unemployed. I: Lifestyle, diagnoses, treatment and re
      employment.
AB  - OBJECTIVE: To describe morbidity, lifestyle and re-employment in a representative
      sample of unemployed people. DESIGN: A two-year follow up of a routine health
      examination consisting of a structured interview, a clinical examination and the
      doctor's conclusions and advice. SETTING: Four municipalities in Greenland,
      southern Norway. PARTICIPANTS: A representative sample aged 16 to 63 who had been
      registered with the labour market authorities for more than 12 weeks. RESULTS:
      Self-reported diseases were more common in the study group than were found in
      employed people, especially musculoskeletal and mental disorders. The prevalence
      of medical diagnoses was high. Smoking was reported by nearly twice as many
      unemployed as the reference population. Heavy alcohol consumption was more
      prevalent in the unemployed men. Blood pressure was lower than in the reference
      population. Cholesterol was higher in the unemployed women. Many needed
      counselling or referrals. Having a medical diagnosis reduced the chances of re
      employment two years later. Thus, health-related selection for re-employment
      seems to explain some of the excess morbidity among unemployed people.
      CONCLUSION: The long-term unemployed is a group with high morbidity and unhealthy
      lifestyle. General practitioners should be aware of this pattern in clinical and
      preventive work.

PMID- 8272656
TI  - Headache and neck or shoulder pain--frequent and disabling complaints in the
      general population.
AB  - OBJECTIVE: to describe the prevalences of reported headache and neck or shoulder
      pain as unspecified complaints, and to explore the consequences of these
      complaints measured as unfitness for work. DESIGN: self-administered
      questionnaire as part of a general health screening. SETTING: all persons aged
      between 20 and 56 years, in the municipality of Tromso were invited. Of 29,026
      invited, 21,826 attended, and of these 20,026 answered the questionnaire. Some
      17,700 answered the questions on headache, and 17,650 on neck or shoulder pain.
      RESULTS: 6.0% of the males reported weekly or more frequent headache, and 15.4%
      reported neck or shoulder pain. The corresponding prevalences in women were 13.1%
      and 24.9%. This female preponderance was present also among subjects expressing
      the complaints daily or monthly. The prevalences of reported neck or shoulder
      pain increased significantly with age, while the prevalences of reported headache
      were not influenced by age. Of the subjects with weekly headache, as many as 30%
      of both sexes reported being "seriously hampered or unable to perform ordinary
      work". CONCLUSIONS: many people in the general population live with disabling
      complaints, but the numbers seeking medical care for them are far fewer. It is
      important to demonstrate the high prevalence of headache and neck or shoulder
      pain, and also to understand the complexity of the causal factors, and the reason
      why only a proportion of sufferers seek professional help.

PMID- 8272657
TI  - Cluster analysis: a perspective.

PMID- 8272658
TI  - Approaches to disease cluster investigations in a state health department.
AB  - Classical tests for clustering rarely have a major role in the investigation of
      disease clusters at the neighbourhood level performed by a health department.
      When examining a single cluster, the boundaries are often ill-defined, and the
      dimension (geographic, occupational, iatrogenic) is rarely obvious. Furthermore,
      using cluster tests to routinely scan disease registries looking for clusters is
      undesirable for several reasons. A better approach is to be vigilant for unusual
      environmental exposures, and to evaluate the impact they may have. In this
      context, cluster techniques may serve as part of a larger investigation that
      includes other epidemiologic approaches.

PMID- 8272659
TI  - Solving the cluster puzzle: clues to follow and pitfalls to avoid.
AB  - Dozens of methods have been proposed for the identification of disease clusters,
      although only a few are used routinely in published investigations. New methods,
      although designed to exploit some particular aspect of the data or use some
      specific statistical tool, are rarely compared thoroughly in terms of power or
      performance. Users, when confronted with the multitude of methods available,
      often select methods arbitrarily, basing choices on software availability, ease
      of implementation, or use experience rather than considerations of statistical
      power, possible alternative hypotheses (that is, cluster structure) and likely
      confounding. In this review, we extend our typology of disease clustering methods
      and apply it to many of the extant methods identifying strengths, weaknesses and
      unique features of the methods. We conclude with recommendations for which
      methods should be applied to which types of situations.

PMID- 8272660
TI  - Disease clusters, exact distributions of maxima, and P-values.
AB  - This paper presents combinatorial (exact) methods that are useful in the analysis
      of disease cluster data obtained from small environments, such as buildings and
      neighbourhoods. Maxwell-Boltzmann and Fermi-Dirac occupancy models are compared
      in terms of appropriateness of representation of disease incidence patterns
      (space and/or time) in these environments. The methods are illustrated by a
      statistical analysis of the incidence pattern of bone fractures in a setting
      wherein fracture clustering was alleged to be occurring. One of the
      methodological results derived in this paper is the exact distribution of the
      maximum cell frequency in occupancy models.

PMID- 8272661
TI  - Assessing directional effects in spatial data.
AB  - A variable is measured at two locations separated by a given distance. Are the
      values more similar to each other if the locations are oriented in one direction
      than another? This question has application to studies of human genetics,
      epidemics, and acid rain. One obvious analytic approach, regression on latitude
      and longitude, fails when data are non-directional (isotropic) but spatially
      autocorrelated. Moreover, although non-zero slope implies similarity between
      neighbours, the converse is not true. IDIFF, a statistic derived from Moran's
      coefficient of spatial autocorrelation, is developed to detect general
      directional effects that apply to the collection of data points. Simulations
      suggest that, when data have isotropic spatial autocorrelation but are
      incorrectly assumed to be independent, IDIFF will at worst reject too little.
      IDIFF has good power to distinguish epidemics that spread non-directionally from
      those that spread in a favoured direction.

PMID- 8272662
TI  - Analysing post-alarm data in a monitoring system in order to accept or reject the
      alarm.
AB  - In a disease monitoring system embracing several diseases and communities, alarms
      indicating a significant increase in disease incidence will frequently occur even
      though the false alarm rate has been set quite low. An approach is presented by
      which an alarm is determined as either confirmed or rejected according to data
      observed subsequent to the alarm. The suggested procedure is expected to weed out
      a substantial proportion (say about 75 per cent) of the false alarms at the
      expense of some delay in detecting a true alarm.

PMID- 8272663
TI  - Properties of Tango's index for detecting clustering in time.
AB  - Tango proposed an index for detecting disease clustering in time applicable to
      grouped data obtained from a population that remains fairly stable over the study
      period. In this paper, we show that Tango's index is a two-dimensional U
      statistic having an asymptotic normal distribution. To apply this result in the
      finite sampling situation, an Edgeworth expansion is used and is shown to be at
      least as accurate as Tango's best result in approximating the tails of his test
      statistic under the null hypothesis. This is extended to show that the Edgeworth
      expansion can be used to approximate the power of Tango's test statistic under
      selected alternatives to randomness. A power study based on simulations is
      conducted to compare the power of Tango's index to that of three of its
      competitors.

PMID- 8272664
TI  - Power of the scan statistic for detection of clustering.
AB  - The scan statistic is the maximum number of events in an interval of fixed length
      w as the subinterval moves over the entire time frame. Previous research derived
      the null distribution of the scan statistic under the conditional model which
      assumed that the total number of events was fixed, and under the unconditional
      model which let the total number of events be a random variable. This paper
      derives approximations for the power of the scan test for a pulse alternative.
      Under this alternative, the relative risk of disease on a subinterval (tau, tau +
      w), tau unknown, is theta-fold as high as it is for other subintervals of length
      w. Two sets of approximations are given for each model. The first approximation
      gives highly accurate results, but requires use of a personal computer. The
      second procedure can be performed on a hand-held calculator and appears very
      accurate for the cases examined.

PMID- 8272665
TI  - Approximations for the tail probabilities and moments of the scan statistic.
AB  - The scan statistic is used to test the hypothesis that the observed events occur
      at random (uniformly distributed) in time or space versus the hypothesis that
      they cluster within a moving window of size w. To implement the testing procedure
      based on the scan statistic its tail probabilities have to be effectively
      evaluated. In this article a survey of results on the approximations of the
      distribution of the scan statistic and its moments is presented. Numerical
      results comparing these approximations are also given. Numerous references with
      applications in epidemiological studies using the scan statistics are mentioned.
      Related scan statistics that have been used in many other interesting
      applications are listed in the reference section. The article concludes with the
      presentation of unsolved problems related to the scan statistic.

PMID- 8272666
TI  - Effect of relative risk and cluster configuration on the power of the one
      dimensional scan statistic.
AB  - The scan test for clustering in time is based on the maximum number of events in
      an interval (window) of width w as the window moves across the entire time frame.
      Power estimates of the scan statistic are simulated for a variety of
      epidemiologically motivated situations. Two cluster configurations are used: a
      rectangular pulse, and a triangular pulse designed to emulate environmental
      contamination. For a rectangular pulse, the relative risk R of disease in the
      cluster region is R-fold as high as it is for the background region. The power is
      strongly influenced by the sample size, the relative risk, and the width or
      duration of the cluster region, whereas the effect of the cluster configuration
      is small. Using a 5 per cent significance level, a relative risk of 4, a
      standardized cluster duration of 0.10, a relative window width of 1.5, and a (non
      random) sample size of 50, the simulated power is approximately 80 per cent,
      indicating that the minimum sample size in the cluster region for adequate power
      is in the 12-32 range for values of the parameters used in this study.

PMID- 8272667
TI  - The effects of scale on tests for disease clustering.
AB  - Surveillance of a large geographic region for 'clusters' of adverse health
      events, particularly cancers, often involves searching for raised incidence in
      the vicinity of prespecified putative sources of hazard. For reasons of
      practicality or of confidentiality, incidence and population data are usually
      only available aggregated over subregions or 'cells'. The performance of
      statistical procedures designed to detect the presence of clusters can be highly
      sensitive to the level of aggregation, that is to the choice of partition of the
      region into the cells. We investigate this sensitivity in the cases of three
      recently proposed procedures, namely those of Besag and Newell, Stone, and Waller
      et al. For illustration, we use leukaemia incidence data for 1978-82 in a region
      of upstate New York, with inactive hazardous waste sites containing
      trichloroethylene acting as suspected sources.

PMID- 8272668
TI  - Assessing spatial patterns in disease rates.
AB  - We describe the empirical performance of three indices of spatial autocorrelation
      (Moran's I, Geary's c and a rank adjacency statistic D) in the analysis of
      regional cancer incidence data. Heterogeneity in regional population sizes and
      age structure leads to variable precision in estimated rates; the usual methods
      for assessing I, c and D, which ignore such heterogeneity, are shown to be
      liberally biased, especially for c and D. The power of these indices to detect
      likely disease patterns is estimated by stimulation; the power is quite variable,
      depending on the exact pattern assumed, although I tends to have the highest
      power. The null distributions appear quite robust in small samples, even when
      several regions have no observed case. Preliminary work on the Ontario cancer
      registry showed generally unimportant effects on the spatial analysis of
      variation in case registration rates or missing residence data.

PMID- 8272669
TI  - Disease mapping using empirical Bayes and Bayes methods on mortality statistics
      in The Netherlands.
AB  - Data from the 64 public health service districts in the Netherlands, describing
      the health status of the Dutch population, were used to construct maps for
      several causes of deaths. The choice and estimation of the relative risk measure
      is described. The prior expected number of deaths was modelled using a Poisson
      regression approach based on a model with main effects of district and age.
      Desirable properties of risk parameters for disease mapping are that they both
      reflect the level of risk and cope with the instability in the observed measure
      caused by the numbers at risk in each district. Different techniques for
      estimation of parameters were applied: empirical Bayes estimation (EB) using a
      nonparametric prior and a gamma prior, and a Bayesian approach (B) with a uniform
      prior. For the parametric EB also a constrained estimator was used. The EB
      techniques studied in this paper shift or smooth the values of the risk parameter
      towards a global mean. In the Bayesian method applied here, spatial dependence
      among districts can be modelled, that is the estimates are smoothed towards a
      local mean. The three EB estimates gave by and large similar results, although
      the constrained EB estimate smoothed less, as was expected. The Bayesian
      estimates smoothed the estimates more or less similarly to the constrained EB.

PMID- 8272670
TI  - Aggregation of existing geographic regions to diminish spurious variability of
      disease rates.
AB  - The availability of large data sets together with the growth in power and storage
      capabilities of computers have made the analysis of the spatial distribution of
      disease rates an increasingly important tool in public health research. Use of
      existing geographic divisions or groupings tends to result either in unstable
      estimates of disease rates if the corresponding populations are small or in loss
      of spatial resolution if the areas are unnecessarily large. This paper describes
      a computer algorithm for combining existing geographic areas into regions with
      populations large enough to diminish spurious variability in disease rates while
      limiting the loss in resolution. The method is demonstrated using Medicare
      hospital admissions data for pneumonia and central nervous system cancer. Disease
      rates were calculated for both predefined regions and those generated by the
      algorithm and their frequency distributions were compared. The algorithm produces
      more stable rates over a variety of diseases and provides substantially more
      flexibility than the use of predefined aggregations.

PMID- 8272671
TI  - Synthetic cancer variables and the construction and testing of synthetic risk
      maps.
AB  - Cancer cluster investigations are usually univariate in nature; they focus on a
      particular cancer, such as leukaemia, and attempt to determine whether excess
      risk is associated with a suspected cancer-causing agent. Although several causes
      of death (such as leukaemia, lymphoma, Hodgkin's) may be considered, the approach
      is univariate because the causes of death are analysed sequentially and
      independently of one another. This approach is consistent with a one-cause one
      effect model. Rarely, however, is the action of a carcinogen manifested at only
      one body site, and correlations among causes of death are the norm rather than
      the exception. A multiple effects model is therefore appropriate, and the
      multivariate nature of cancer mortality data should be exploited when exploring
      geographic pattern in cancer risks. This paper describes such an approach. We
      construct maps based on a principal components analysis of cancer mortality rates
      from different geographic areas. The resulting principal components are called
      synthetic cancer variables (SCVs), and maps of the SCV scores are synthetic risk
      maps (SRMs). These maps quantify geographic variation in cancer risk at several
      body sites simultaneously, and may be analysed for (1) spatial structure and (2)
      geographic association with potential risk factors. As an example, we use
      synthetic risk maps to determine whether high-risk counties in Illinois cluster
      near nuclear facilities. Much work remains to be done, but synthetic cancer risk
      maps appear to be a useful tool for quantifying geographic pattern and
      multivariate structure in cancer mortality.

PMID- 8272672
TI  - Mixture models and disease mapping.
AB  - The analysis and recognition of disease clustering in space and its
      representation on a map is one of the oldest problems in epidemiology. Some
      traditional methods of constructing such a map are presented. An alternative
      approach using mixture models to identify population heterogeneity and map
      construction within an empirical Bayes framework is described. For hepatitis B
      data from Berlin in 1989, a map is presented and the different methods are
      evaluated using a parametric bootstrap approach.

PMID- 8272673
TI  - Interfacing U.S. census map files with statistical graphics software: application
      and use in epidemiology.
AB  - In 1990, the United States Bureau of the Census released detailed geographic map
      files known as TIGER/Line (Topologically Integrated Geographic Encoding and
      Referencing). The TIGER files, accessible through purchase or federal repository
      libraries, contain 24 billion characters of data describing various geographic
      features including coastlines, hydrography, transportation networks, political
      boundaries, etc. for the entire United States. Many of these physical features
      are of potential interest in epidemiological case studies. Unfortunately, the
      TIGER data base only provides raw alphanumeric data; no utility software,
      graphical or otherwise, is included. Recently, the S statistical software package
      has been extended to include a map display function. The map function augments
      S's high-level approach towards statistical analysis and graphical display of
      data. Coupling this statistical software with the map data base developed for
      U.S. Census data collection will facilitate epidemiological research. We discuss
      the technical background necessary to utilize the TIGER data base for mapping
      with S. Two types of S maps, segment-based and polygon-based, are discussed along
      with methods to construct them from TIGER data. Polygon-based maps are useful for
      displaying regional statistical data, such as disease rates or incidence at the
      census tract level. Segment-based maps are easier to assemble and are appropriate
      when the data are not regionalized. Census tract data of AIDS incidence in San
      Francisco and lung cancer case locations relative to petrochemical refinery sites
      in Contra Costa County are used to illustrate the methods and potential uses of
      interfacing the TIGER data base with S.

PMID- 8272674
TI  - Computer packages C.A.MAN (computer assisted mixture analysis) and Dismap.

PMID- 8272675
TI  - The statistical description of disease clusters.

PMID- 8272676
TI  - Nurse practitioner-patient discourse: uncovering the voice of nursing in primary
      care practice.
AB  - This study focused on nurse practitioner-patient conversations. The purpose was
      to uncover a process that might contribute to understanding the positive outcomes
      of nurse practitioner (NP) care. Transcripts from 24 audiotaped NP-patient
      conversations and three NP-researcher interviews, as well as 100 hours of field
      notes from observations, were analyzed using a combination of discourse and
      ethnographic analysis.

PMID- 8272677
TI  - A construct validity study of a Differentiation of Self Scale.
AB  - The purpose of this study was to establish construct validity of the Haber Level
      of Differentiation of Self Scale (LDSS) that measures selected aspects of the
      construct, differentiation of self, the key concept of the Bowen Theory. During
      stage one of this study, a 32-item Likert-type LDSS, which contained two
      subscales, Emotional Maturity, (EM), and Emotional Dependency (ED), was
      administered to 372 volunteer subjects. Factor analytic and correlational
      findings indicated support for a 24-item unidimensional rather than a 32-item two
      subscale instrument. Recalculation of coefficient alpha (.90) also supported the
      unidimensional structure of the LDSS. During stage two of this study, the revised
      24-item LDSS was administered to 372 volunteer subjects, who also completed the
      State-Trait Anxiety Inventory, the Life Experience Survey, and the Behavior
      Checklist. Hypotheses predicted that there would be negative relationships
      between differentiation of self and trait anxiety, state anxiety, adult
      psychological dysfunction, and negative impact stress. Findings indicate support
      for all hypotheses at the p < .01 level of significance or greater. Data from
      this study suggest that the 24-item LDSS is a valid and reliable unidimensional
      family assessment tool that accurately measures specific aspects of the
      construct, differentiation of self. The LDSS can be used by nurses and other
      professionals to assess individual and family functioning in a variety of health
      care settings.

PMID- 8272678
TI  - Experienced and skilled nurses' narratives of situations where caring action made
      a difference to the patient.
AB  - Forty-five skilled and experienced nurses working at long-term, medical and
      surgical care clinics narrated 88 caring situations. The aim of the study was to
      interpret these narratives concerning the nurses' caring actions and the type of
      situations where they experienced that their caring made a difference to the
      patient. There were eight types of caring actions that were then condensed into
      three interaction and intervention approaches; 1) deliberate distanced
      interaction and intervention with the patient; 2) deliberate providing of
      prerequisites for interaction and intervention with the patient; and 3)
      deliberate deep interaction with the patient when intervening. These approaches
      were used when the nurses dealt with the following three types of caring
      situations: caring focusing on the nurse-patient relationship, on medical
      intervention, and on practical problem solving. The first two approaches occurred
      in situations focusing on acute medical intervention and on practical problem
      solving. All approaches occurred in situations focusing on the nurse-patient
      relationship. The finding that experienced and skilled nurses described
      situations where the depth of their contact with the patient varied can be
      expressed in the phrase "how I act depends on the situation." The skill to find
      the right level of involvement seems important.

PMID- 8272679
TI  - Predictors of children's self-care performance: testing the theory of self-care
      deficit.
AB  - Orem's theory of self-care deficit proposes relationships between self-care
      performance and (a) basic conditioning factors, (b) self-care agency, and (c)
      dependent-care agent performance. The purpose of this study was to examine these
      proposed relationships in children. The study sample was composed of 414 students
      in grades 4 through 12, ages 9 through 18 years. Using regression analyses, study
      findings were that the variables chosen to represent the basic conditioning
      factors together accounted for 19% of the variance in children's self-care
      performance. Separately, both age and health state were significant predictors.
      Additionally, when self-care agency was added to the regression model, the
      combination accounted for 36% of the variance. A correlational analysis showed a
      moderate relationship between a child's self-care performance and her or his
      mothers' dependent-care agent performance. Future research should continue to
      investigate Orem's theories and the operationalization of the concepts.

PMID- 8272680
TI  - [Hyperlipidemia and atherosclerosis: epidemiology, biochemistry and therapy].
AB  - Cardiovascular diseases cause 40% of deaths in Belgium. The coronary risk is more
      important in the Southern than in the Northern part of the country, owing
      probably to different levels of serum cholesterol due to different fat contents
      of the diet. The features of lipoprotein metabolism are mainly the permanent
      transfer of apoproteins and the dynamic exchange of neutral lipids. Atherogenic
      particles include remnants enriched in cholesterol esters and low density
      lipoproteins (LDL) after their oxidation. New European guidelines insist more on
      secondary prevention than on primary prevention.

PMID- 8272681
TI  - [Revision of acetabular loosening using an acetabular shell with screws].
AB  - The different techniques for the revision of the acetabular loosening are
      reviewed. In our department, we use the acetabular flanged shell fixed with
      screws. Three cases illustrate this promising process.

PMID- 8272682
TI  - [Fetal cardiology: prenatal diagnosis of cardiac malformations].
AB  - Foetal cardiology is now a recognised chapter of both paediatric cardiology and
      foetal medicine. We describe here our experience with antenatal diagnosis of
      cardiac malformations and discuss both its genetic and epidemiological issues.
      Our experience confirms if need be that foetal medicine requires a well organised
      first-level foetal evaluation.

PMID- 8272683
TI  - [Consensus in matters of prevention in the general practitioner's office].

PMID- 8272684
TI  - [Toxicity of NSAIDs].

PMID- 8272685
TI  - Metabolic effects of oral contraceptives. Implications for exercise responses of
      premenopausal women.

PMID- 8272686
TI  - Gender verification in competitive sports.
AB  - The possibility that men might masquerade as women and be unfair competitors in
      women's sports is accepted as outrageous by athletes and the public alike. Since
      the 1930s, media reports have fuelled claims that individuals who once competed
      as female athletes subsequently appeared to be men. In most of these cases there
      was probably ambiguity of the external genitalia, possibly as a result of male
      pseudohermaphroditism. Nonetheless, beginning at the Rome Olympic Games in 1960,
      the International Amateur Athletics Federation (IAAF) began establishing rules of
      eligibility for women athletes. Initially, physical examination was used as a
      method for gender verification, but this plan was widely resented. Thus, sex
      chromatin testing (buccal smear) was introduced at the Mexico City Olympic Games
      in 1968. The principle was that genetic females (46,XX) show a single X-chromatic
      mass, whereas males (46,XY) do not. Unfortunately, sex chromatin analysis fell
      out of common diagnostic use by geneticists shortly after the International
      Olympic Committee (IOC) began its implementation for gender verification. The
      lack of laboratories routinely performing the test aggravated the problem of
      errors in interpretation by inexperienced workers, yielding false-positive and
      false-negative results. However, an even greater problem is that there exist
      phenotypic females with male sex chromatin patterns (e.g. androgen insensitivity,
      XY gonadal dysgenesis). These individuals have no athletic advantage as a result
      of their congenital abnormality and reasonably should not be excluded from
      competition. That is, only the chromosomal (genetic) sex is analysed by sex
      chromatin testing, not the anatomical or psychosocial status. For all the above
      reasons sex chromatin testing unfairly excludes many athletes. Although the IOC
      offered follow-up physical examinations that could have restored eligibility for
      those 'failing' sex chromatin tests, most affected athletes seemed to prefer to
      'retire'. All these problems remain with the current laboratory based gender
      verification test, polymerase chain reaction based testing of the SRY gene, the
      main candidate for male sex determination. Thus, this 'advance' in fact still
      fails to address the fundamental inequities of laboratory based gender
      verification tests. The IAAF considered the issue in 1991 and 1992, and concluded
      that gender verification testing was not needed. This was thought to be
      especially true because of the current use of urine testing to exclude doping:
      voiding is observed by an official in order to verify that a sample from a given
      athlete has actually come from his or her urethra. That males could masquerade as
      females in these circumstances seems extraordinarily unlikely. Screening for
      gender is no longer undertaken at IAAF competitions.

PMID- 8272687
TI  - Bone mineral density and long term exercise. An overview of cross-sectional
      athlete studies.
AB  - Evidence in human studies of the association of long term habitual exercise with
      bone mineral content (BMC) and density (BMD) largely comes from studies in
      athletes. In young adults, the highest BMC and BMD values have been found in
      strength and power-trained athletes, while endurance activities such as long
      distance running and swimming seem less effective with regard to peak bone
      density. Intensive endurance training may even be associated with amenorrhoea and
      decreased trabecular bone density in young females. However, after menopause
      female athletes show greater bone mass indicating that they do not share the
      accelerated decline in BMC observed in a nonathletic population. Middle-aged and
      elderly male athletes from various sports have significantly higher BMC and BMD
      than controls, especially in trabecular bone sites, but higher cortical BMC has
      also been found in the dominant/nondominant arm comparisons with unilateral
      exercises such as tennis. The differences found between female athletes and
      controls have generally been less pronounced than those among men, but a number
      of studies suggest that in women long term physical training may counteract the
      low BMC and BMD associated with reduced bone mass. Although the interpretation of
      results of cross-sectional studies should be treated with caution, studies in
      athletes serve as an economical alternative approach to experimental trials with
      their long term follow-up and exercise compliance problems. The differences found
      in BMD between those who have devoted themselves to life-long training and those
      who have been much less active should not be underestimated.

PMID- 8272688
TI  - Endurance training, cardiovascular function and the aged.
AB  - Independent of disease, age-associated changes in cardiovascular function include
      anatomical, physiological, and haemodynamic alterations that are generally
      without pathological consequence. Decrements in adrenergic receptor response,
      arterial distensibility, ventricular compliance, and contractile performance seem
      to be compensated for by enhanced atrial contribution to ventricular filling,
      prolongation of systole, and increased reliance on the length-tension
      relationship of cardiac muscle. Summarily, these compensations constitute
      increased utilisation of the Frank-Starling mechanism. Endurance training
      beneficially alters aging cardiovascular function both at rest and during
      exercise. An increase in end diastolic volume and ejection fraction demonstrate
      an enhancement of the length-tension relationship of myocardial tissue in
      maintaining resting and exercise cardiac outputs. The decline in maximal
      cardiovascular function is not preventable. It was also concluded that endurance
      exercise improves clinical and psychosocial factors that enhance the quality of
      life for elderly individuals. Future research efforts should attempt to determine
      if and by what mechanisms endurance training may contribute to the regression of
      atherosclerotic lesions and the development of collateral vessels in senescent
      myocardium.

PMID- 8272690
TI  - Chronic lateral instability of the ankle in athletes.
AB  - Acute lateral ligament injuries of the ankle are best treated nonsurgically, with
      peroneal strengthening and neuromuscular training. At least 80 to 90% of patients
      will regain satisfactory ankle stability after functional treatment. Chronic
      ankle instability occurs in approximately 10 to 20% of patients after acute
      ligament injuries, irrespective of primary treatment. Surgical reconstruction may
      be necessary, especially in athletes with high demands on ankle joint stability.
      Numerous different surgical procedures have been described many with some kind of
      a tenodesis. The classic tenodeses, Evans, Watson-Jones and Chrisman-Snook, have
      all been used with good short term results. Anatomical ligament reconstruction
      using the remnants of the ruptured and elongated ligaments, with shortening,
      reinsertion and duplication, have been shown to be simple, effective and free
      from complications. As the results of anatomical reconstruction are satisfactory
      both in the short and the long term, this reconstruction is recommended for
      correction of lateral ankle instability.

PMID- 8272691
TI  - [What is your diagnosis? Acute edematous senile polyarthritis (RS3PE syndrome)].

PMID- 8272689
TI  - Long term effects of closed head injuries in sport.
AB  - Closed head injury has been defined by several authors, but is not agreed upon.
      The incidence of closed head injury in sports is relatively small, but because
      the effects may be catastrophic it is an important topic. Forces may be applied
      to the head from different directions, which results in different types of
      lesions. The anatomical and physiological changes with head injury have been
      suggested to explain head injury outcomes. Effects on intelligence and memory
      have also been reported. Posture had been proposed as a model to examine the
      subtle effects of head injury. Vision, vestibular input, and somatosensory input
      are all involved in maintenance of posture. The interaction of these sensory
      modalities is also pertinent to posture maintenance. Somatosensory input appears
      to be improperly processed, while vision and vestibular input seem to compensate
      for lost somatosensation. Attention to regaining the somatosensory component,
      rather than waiting for compensation to occur, should be addressed in
      rehabilitation programmes.

PMID- 8272692
TI  - [Correlation between disorders of lipid metabolism and hypertension in 10,892
      participants in the Heureka Study].
AB  - Hypertension and hyperlipidemia belong to the most important and most frequent
      cardiovascular risk-factors. It is known that hypertensive patients show
      hypercholesteremia more often than normotonic persons and some of the mechanisms
      causing this unfavourable combination seem to be disclosed. METHOD AND RESULTS:
      During the important Swiss research-exhibition Heureka (april to november 1991)
      in Zurich, blood pressure (BD), pulse, cholesterol and in 822 probands
      additionally HDL, were investigated in 11,997 volunteers. Cardiovascular risk
      factors were registered by means of a questionnaire. 10,892 completed
      questionnaires (5973 female, 4919 male probands) could be used for this analysis
      intended to answer the question whether a relation between blood pressure and
      cholesterol exists. Stratification and multivariate analysis allowed
      consideration of certain factors that could possibly influence the results
      (anthropometry, age). A separate multiple linear regression analysis with
      cholesterol as dependent variable was made for female and male probands
      respectively whereby regression coefficients for systolic and diastolic blood
      pressure values remained significant (p < 0.001). In the highest cholesterol
      quintile 36.4% hypertensive probands (in the lowest 6%) were found. Distribution
      of cholesterol was distinctly different in a group with diastolic blood pressure
      values < 70 mmHg compared to the group with values > 100 mmHg. Higher diastolic
      pressures were associated with higher cholesterol values even after
      stratification in age-classes and diastolic pressure classes. CONCLUSIONS: These
      results underline the hypothesis, that cholesterol modifies blood pressure. Thus
      the relevance of a disturbed lipid metabolism for accompanying hypertension seems
      to be confirmed and an adapted antihypertensive therapy considering all risk
      factors is proposed as the most successful strategy.

PMID- 8272693
TI  - [Campaign against smoking and the general practitioner. Evaluation of a simple
      method allowing immediate measurement of compliance with smoking cessation in the
      physicians office].
AB  - Recently, the Swiss Medical Association and the Swiss Federal Office for Public
      Health started a campaign against smoking. Portable carbon monoxide (CO) devices
      measuring alveolar CO concentration are now available. It is important to know
      how accurate they are in discriminating smokers (S) from nonsmokers (NS) in
      different environmental conditions. We administered a smoking questionnaire and
      measured alveolar CO concentration in 241 people living in an urban area (PU) and
      112 people living in a mountain area (PM). Smoking prevalence was 39% in PU and
      17% in PM. Alveolar CO concentration was significantly higher in S than in NS (27
      +/- 11, 11 to 60, vs. 14 +/- 9, 4 to 52, p < 0.01 in PU and 23 +/- 13, 4 to 48,
      vs. 9 +/- 7, 4 to 46, p < 0.01 in PM). We found significantly higher CO-values in
      NF of PU than PM (p < 0.01). This test has a sensitivity of 80%, a specificity of
      78%/79% (PU/PM) and a predictive positive value of 74%/80% (PU/PM). The cut-off
      point has to be adapted depending on the environmental exposure (PU: 15 ppm, PM:
      10 ppm CO). Alveolar CO measurement is a cheap accurate method whose results are
      immediately available to the general practitioner in his fight against smoking.
      This method merits higher application.

PMID- 8272694
TI  - [Gastrointestinal hemorrhage: how much evaluation is necessary?].
AB  - For this study data from a total of 362 patients covering a time period of 10
      years (1979-1989) were analyzed. Referal to the medical outpatient clinic of
      Zurich occurred in over 90% of the cases for evaluation of incidental iron
      deficiency anemia or suspected of gastrointestinal bleeding because of
      melanea/hematemesis. The evaluation comprised endoscopy, in part radiography of
      the upper intestinal tract and rarely angiography and scintigraphic tracer
      studies. 95 patients (26%) had benign lesions in the gastro-intestinal tract, 88
      patients (26%) had endoscopy without abnormal findings. Iron deficiency was
      thought to be due to hypermenorrhea in 45 patients (13%) and to other non
      gastrointestinal causes in 43 patients (13%) by exclusion. A malignancy of the
      gastrointestinal tract was found in 25 patients (7%): 18 carcinomas of the colon,
      6 carcinomas of the stomach and 1 metastasis of a melanoma to the coecum. In 80%
      of the patients with malignancies occult fecal blood was detected. In 154
      patients (42%) extensive diagnostic investigation including sometimes even
      repeated endoscopy could not disclose the cause of blood loss. 88 (24%) of these
      patients had slight iron deficiencies (hemoglobin > 10 g/dl, hemoccult-test
      positive in 65% of cases), 66 (18%) had severe iron-deficiencies (hemoglobin < 10
      g/dl, hemoccult-test positive in 90% of cases). Selective small bowel radiography
      was performed in 36 patients without any positive findings. Patients with gastro
      intestinal bleeding of undetermined etiology present a diagnostic challenge for
      the general practitioner.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272696
TI  - [What is your diagnosis?].

PMID- 8272695
TI  - [Quantitative assessment of the quality of life of patients with a kidney
      transplant].
AB  - Actually three methods are offered for the treatment of patients with chronic
      renal failure: 1. Hemodialysis, 2. chronic peritoneal dialysis for outpatients
      (CAPD) and 3. Transplantation of a kidney. In order to define the optimal therapy
      for these patients not only economic factors but also quantitative evaluation of
      life quality has to be taken into account. To this end a questionnaire called
      "Sickness Impact Profile", that covers most of the relevant features of life and
      is well established in the Anglo-Saxon countries, was translated into German
      language and tested in 34 hemodialysis-patients, 25 CAPD-patients and 29 patients
      with kidney transplant, in order to investigate the applicability. Results showed
      that the German issue can successfully be applied to Swiss patients with renal
      failure and lead to the conclusion that--in accordance to results of similar
      studies in the USA--life quality in patients with kidney transplant is better
      than in patients treated with hemodialysis or CAPD.

PMID- 8272697
TI  - [Morphological basis of atherosclerosis].
AB  - The lesions of atherosclerosis are initiated as a response to some form of injury
      to arterial endothelium. Increase in plasma levels of low-density lipoproteins or
      some components of hyperlipidemic serum may increase the rate of penetration into
      the artery wall. Monocytes adhere to endothelium, emigrate into the intima and
      transform into lipid-laden macrophages. The second component of atherogenesis is
      smooth muscle proliferation in the intima. The proliferating cells originate from
      cells migrating from the media and from myointimal cells. After adhesion to foci
      of injury, platelets release platelet-derived growth factor, a potent mitogen for
      intimal smooth muscle cells. The plaque is increasing, the lumen narrowing. A
      plaque consisting mainly of yellow, grumous fluid is called an atheroma. The oily
      content of this plaque is covered by a fibrous cap that is often thin and prone
      to rupture. An occluding thrombus may result. Lipids and crystalline cholesterol
      initiate a foreign-body reaction, an inflammatory process. Older lesions are
      calcified. Examples from the daily work in the mortuary demonstrate the
      pathogenetic relevance of hypertension, thrombocytes and endothelium.

PMID- 8272698
TI  - [The metabolic syndrome: common etiology for distinct cardiovascular risk
      factors?].
AB  - Hypertension, dyslipidemias, glucose intolerance and obesity are among the most
      important cardiovascular risk factors. There is growing evidence for the concept
      of a relationship between blood pressure regulation and metabolic changes. The
      combination of hypertension and the metabolic changes mentioned above has been
      named metabolic syndrome in the literature. The central role of insulin
      resistance and consecutive hyperinsulinemia in the metabolic syndrome has been
      shown in epidemiological, clinical, genetic and animal studies. The metabolic
      syndrome can be demonstrated in about one half of the hypertensive population.
      This pathophysiological concept has to be taken into consideration in the therapy
      and prevention of the different cardiovascular risk factors.

PMID- 8272699
TI  - [Lipids and blood vessels].
AB  - The key lesion in atherosclerosis is termed atheroma. It consists of
      intracellular and extracellular cholesterol esters. Because atheromas are located
      subendothelially, an interrelation with blood cholesterol has long been
      suspected. In the blood, cholesterol is wrapped in lipoproteins, with the largest
      amount being found in low-density lipoproteins (LDL), whereas a smaller amount is
      found in high-density lipoproteins (HDL). LDL (and their cholesterol) are removed
      from the plasma by receptor-mediated uptake. Impaired LDL-receptor interaction
      results in accumulation of LDL in plasma. LDL now penetrate the endothelial layer
      and become deposited in the arterial intima. This process initiates atheroma
      formation. Excess tissue cholesterol (e.g. in the arterial intima) is returned to
      the liver by HDL. The HDL2 subfraction is particularly effective in this reverse
      cholesterol transport. Patients with coronary atherosclerosis either have a
      defect in reverse cholesterol transport (i.e. low HDL2 levels) or an excess in
      cholesterol load (i.e. high LDL). The ratio between LDL and HDL2 cholesterol
      determines the risk for atherosclerotic disease. Triglycerides lower HDL2 levels
      and thereby exert indirect atherogenicity.

PMID- 8272700
TI  - [Is regression of coronary sclerosis possible?].
AB  - Randomized studies with sequential coronary arteriographies have clearly
      documented that aggressive lipid-lowering therapy and change in life style can
      reduce progression and produce a modest regression of coronary artery lesions.
      The changes in the extent of a stenosis are determined by the level of
      cholesterol and LDL cholesterol achieved during treatment. Three of the
      randomized studies have shown that the lipid-lowering intervention has not only a
      beneficial influence on the coronary arteriographic lesions, but the number of
      clinical events is reduced as well. The calcium blockers nifedipine and
      nicardipine do not influence progression and regression but reduce the de novo
      appearance of coronary stenoses, either expressed as number of lesions per
      patient or as percentage of patients with new stenoses.

PMID- 8272701
TI  - [Treatment strategies in arterial occlusive diseases].
AB  - The risk factors predominating in patients with peripheral arterial occlusive
      disease are cigarette smoking and diabetes. Moreover, hypertension and
      hyperlipidemia play an important role. Especially younger patients profit from
      elimination or treatment (primary or secondary prevention), whereas in elderly
      patients these measures are no longer crucial. In patients with intermittent
      claudication, the quality of life may be improved by physical training,
      vasoactive medicaments, optimal management of concomitant diseases and the
      different modalities of catheter therapy. According to the special situation in
      critical ischemia, surgical or catheter revascularization is preferred. If these
      two techniques cannot be used, intra-arterial or intravenous prostanoids are
      still promising. Aspirin and in second priority ticlopidine are suited for
      secondary prevention of arteriosclerosis not only in the extracranial, but also
      in the peripheral vascular region. After endarterectomy and catheter therapy,
      aspirin improves the long-term outcome by reducing the incidence of restenoses.
      Better results are obtained by oral anticoagulation in patients with emboli and
      after local thrombolysis.

PMID- 8272702
TI  - [Heureka study: prevalence of overweight and obesity in Switzerland].
AB  - Overweight and obesity as well as associated metabolic disorders belong to the
      most important risk factors. During the exhibition 'Heureka' in Zurich data on
      body weight and size as well as on other clinical and biochemical parameters were
      collected by a questionnaire. Age- and gender-specific prevalence rates were
      calculated. Between 10 and 41% of the visitors showed a body-mass index of > or =
      25 kg/m2, as a function of age and gender -0.7 to 6.2% showed a body-mass index
      of > or = 30 kg/m2. The most important increase in body weight was found in the
      age groups between 20 and 40 years. The presented epidemiologic data show that
      overweight is common in Switzerland, too. Prevention of overweight is still one
      of the most rational medical strategies and should be intensified in the age
      group between 20 and 40.

PMID- 8272703
TI  - [Newer test discovers HIV and genetic defects].

PMID- 8272704
TI  - [What is your diagnosis? Right-sided lumboradicular inflammation syndrome with
      synovial cyst (sacral cyst)].

PMID- 8272705
TI  - [Ethical problems in geriatrics].

PMID- 8272706
TI  - [Significance of after care by family practitioner following myocardial infarct
      from the patient's viewpoint].
AB  - In this study a questionnaire has been sent to 118 male patients about 21 months
      after the first myocardial infarction. The patients in question have suffered a
      first acute myocardial infarction in the second half-year of 1987 and have been
      hospitalized in ten different clinics around Zurich. 80 (72%) of the patients not
      older than 62 years have answered; 4 patients died. The results indicate that the
      treatment by the general practitioner has been assessed mostly positively; 63.7%
      of the patients were very content with the care provided by their general
      practitioner, 32.5% were rather content and only 3.8% were rather discontent.
      Only 5% changed to another general practitioner out of discontentment within the
      mentioned period. 91.2% of the patients taxed the expended time by the general
      practitioner as just about sufficient. Results concern the influence of the
      general practitioner on modification of habits after the myocardial infarction:
      former smokers indicated more often, that the advice of the general practitioner
      has helped them (p < 0.01), those patients who changed their eating habits talked
      more often with their physician about this subject (p < 0.05), respective
      counselling by the general practitioner had an evident influence on the sportive
      activities of the patients (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272707
TI  - [Arthropathy in hemochromatosis].
AB  - Early diagnosis of hemochromatosis may prevent the numerous risks of iron
      overload. One of the most common early manifestations of this disease is
      arthropathy. The clinical and radiologic findings of hemochromatosis arthropathy
      are discussed. Diagnosis is suggested by simple laboratory tests and confirmed by
      liver biopsy with measurement of hepatic iron content. Treatment includes the
      removal of the excess body iron by phlebotomy. Unfortunately, symptoms of
      arthropathy tend to be resistant to phlebotomy.

PMID- 8272708
TI  - [Confronted with mono-arthritis: which tests?].
AB  - A monoarthritis may correspond to a localized inflammatory process or to the
      onset of rheumatoid disease that may later on spread over few or several of the
      other joints. In this article the different diagnostic and therapeutic steps to
      approach monoarthritis are presented. One of the first investigations consists in
      an analysis of the synovial fluid. It should take place before any therapeutic
      step is initiated and may allow to diagnose a microcrystalline or a septic
      arthritis. By means of a literature review monoarthritis is described as a
      disease, whose cause remains often undisclosed inspite of intensive
      investigations, whose further course, however, is often favorable.

PMID- 8272709
TI  - [Abdominal pain, fresh blood in the anus].
AB  - A 60-year-old lady with type II diabetes, arterial hypertension and 'melancholia'
      was treated with Lithium, a neuroleptic (Leponex) and an ACE inhibitor (Reniten).
      She was referred to our hospital because of abdominal pain, subfebrile
      temperatures, diarrhea and hematochezia. The radiological and sonographic
      examinations showed a thickened wall of the left hemicolon. Colonoscopy revealed
      a sharply delineated segment with pronounced inflammation in the descending colon
      and the proximal sigmoid colon, suggestive for an ischemic colitis. Histology of
      the inflamed colon was compatible with this diagnosis. Under suspended enteral
      feeding and antibiotic therapy the symptoms disappeared within two weeks, and a
      control colonoscopy six weeks later was completely normal. 1 1/2 years later the
      patient suffered from a second episode of ischemic colitis exactly a the same
      site. Again, complete cure was achieved by conservative treatment.

PMID- 8272710
TI  - [A case from practice (282). Oncocytoma of the left kidney. Status following
      enucleation 5/92. Atrophic right kidney of unclear etiology. DD: congenital,
      vascular, status following early-childhood recurrent pyelonephritis. Proteinuria
      with intermittent nephritic urinary sediment. Hypertension ].

PMID- 8272711
TI  - [Peters N.: Use of rubber comforter: distribution, causes and sequelae. Schweiz.
      Rundschau Med. (praxis) 82, No.33, 885-887, 1993].

PMID- 8272712
TI  - [Secondary polycythemias: the role of erythropoietin].
AB  - The discovery of high hemoglobin and hematocrit values in a patient necessitates
      the determination of the red blood cell mass in order to confirm the absolute
      character of the polycythemia. If a true polycythemia is confirmed, its etiology
      must then be established. The diagnostic approach of polycythemia is presented in
      this paper. It is illustrated by a case presentation in which a polycythemia
      secondary to a renal carcinoma is discussed. Erythrocytosis is a classical,
      albeit rare manifestation of this type of tumor, and has the advantage of
      allowing early detection. Thus, it permits a prompt treatment plan, thereby
      improving the prognosis of such a neoplasia. The usefulness of a serum level of
      erythropoietin (EPO) is subsequently discussed. The diagnostic value of EPO
      remains controversial because of the overlapping values recorded amongst healthy
      patients, patients with polycythemia vera and others with secondary polycythemia.
      Finally, we discuss the presence of substances in paraneoplastic polycythemias
      whose biological activity is close to that of EPO. However, this molecules of a
      different structure would not be detected by the radioimmunoassay used to measure
      erythropoietin level.

PMID- 8272713
TI  - [Neurological manifestations of Lyme disease].
AB  - Lyme's disease, transmitted by Borrelia Burgdorferi (BB), is a polymorphic and
      multisystemic illness. Its neurological manifestations are encountered in 10-50%
      of cases and occur in the acute disseminated stage as well as in the late stage.
      This article initially reviews the principal clinical pictures of the
      neuroborreliosis and distinguishes them from neurological disorders whose
      association with BB infection is not proven. The paper then discusses the
      relative usefulness of the different ancillary tests in the diagnostic workup. We
      hope to stimulate interest in the research of intrathecal specific antibody
      production (especially in the early central nervous system diseases), instead of
      measuring levels of anti-BB antibodies in the serum and in the cerebrospinal
      fluid. Finally, a treatment plan is proposed, whose efficiency constitutes
      another argument in favor of the correct diagnosis but whose failure may reflect
      a diagnostic error.

PMID- 8272714
TI  - [Chronic urticaria: evaluation and long-term follow-up].
AB  - Two major difficulties occur as soon as one is confronted to a patient suffering
      from chronic urticaria: the determination of an etiology that might be amenable
      to treatment and the establishment of an efficient treatment and satisfying
      follow-up for the patient. After having reviewed the different possible
      etiologies of chronic urticaria, this paper attempts to propose a logical
      diagnostic approach for the primary care physician. This will allow him to
      identify the etiologies that are the most common and responsive to a specific
      treatment and then to detail the modalities of this treatment.

PMID- 8272715
TI  - [Polyglandular autoimmune syndrome].
AB  - Polyglandular autoimmune syndrome (PGA's) are defined as the coexistence of one
      or several primary endocrine gland autoimmune insufficiencies, possibly
      associated with other immunological pathologies. We present the case of a female
      patient suffering from a primary thyroid failure associated with Biermer anemia
      and hypophysitis with secondary adrenal insufficiency. We then describe the
      PGA's, focusing on their interest to the pediatrician, internist, and primary
      case physician. The three types of polyglandular syndromes, types I and II with
      adrenal insufficiency, and type III without it, are discussed. (Classification of
      Neufeld et al.).

PMID- 8272716
TI  - [Importance of infectious diseases and role of the infection specialist in a non
      university hospital].
AB  - More than 3000 infectious diseases treated in the past 10 years at the Department
      of Medicine of the Cadolles Hospital in Neuchatel (Switzerland) have been
      gathered from a computer data base. The infectious disease specialist is directly
      involved in the diagnosis and treatment of the most severe or rare affections.
      However, he influences in a more general fashion the management of anti
      infectious treatments by directing the treatment plan and helping to choose the
      proper antibiotics. He also is responsible for the prevention of nosocomial
      infections. The role and function of the infectious disease specialist as well as
      the importance of this specialty in a community hospital are discussed.

PMID- 8272717
TI  - [Esophageal perforation in a fruitless attempt at endotracheal intubation].
AB  - Esophageal perforation is a rare but potentially serious complication of
      endotracheal intubation, often leading to mediastinitis. The diagnosis should be
      performed rapidly, based on suggestive clinical signs as well as on plain chest
      roentgenograms and contrast esophagogram. The usual treatment consists of broad
      spectrum antibiotherapy, prompt surgical closure of the perforation and adequate
      drainage of the area. The overall mortality rate of about 50% is significantly
      reduced if therapy is begun within the first 12 hours. A number of ancillary
      tests and clinical criteria have been proposed in order to assess difficult
      intubations. The authors report a case of esophageal perforation following a
      difficult intubation, resulting in acute respiratory distress, subcutaneous
      emphysema and bilateral pneumothorax. An early diagnosis and prompt surgical
      treatment facilitated a successful outcome.

PMID- 8272718
TI  - [Late post-traumatic pericardial effusion. Identification of promoting conditions
      and literature review apropos of 2 cases].
AB  - The authors report two cases of post traumatic haemopericardium discovered 18
      days after a iatrogenic penetrating trauma (sternal puncture) for the first one,
      and 102 days after a fall with blunt thoracic trauma and multiple associated
      injuries, for the second one. After admission, the first case rapidly developed a
      severe tamponade requiring a pericardial drainage, of 420 ml of non coagulated
      blood. The second case, in spite of a volume of liquid of more than 1000 ml,
      showed only a fatigue and a dyspnea, without any sign of haemodynamic failure. A
      literature review allows to be more specific about the characteristics of the
      tamponade and the different mechanisms responsible for cardiac injuries connected
      to thoracic traumas. For many reasons, the cardiac damages and/or their
      complications are often misjudged, particularly in thoracic traumas associated
      with multiple lesions. Among the sequelae, pericarditis, with or without
      effusion, is particularly frequent and it is essential to systematically look for
      it before dismissing a patient who went through a thoracic trauma. As for the
      bone marrow sampling, the sternal puncture generates a great number of injuries
      and must be proscribed. The iliac crest puncture should take its place.

PMID- 8272719
TI  - [Myocardial lesion secondary to defibrillation. Literature review and practical
      implications].
AB  - A 39 years old patient was defibrillated during the acute stage of an inferior
      myocardial infarction. He presented an elevation of the ST segment in the right
      precordial leads immediately after resuscitation. The evolution of the
      electrocardiographic changes were characterised by the development of a septo
      apical subepicardial necrosis, whose sequelae remained nine months after the
      initial event. In the absence of any stenosing lesion of the anterior
      interventricular coronary artery, this necrosis can be attributed to the
      electrical shocks. The close position of the defibrillator paddles on the thorax
      certainly played a determining role, exposing the underlying myocardial tissue to
      an excessive electrical intensity. The authors point out the importance of the
      technical modalities of defibrillation that are likely to ensure the best chances
      of success with a minimum of secondary myocardial damage.

PMID- 8272720
TI  - [10 years of medical-hospital data processing. Returns, answers, hazards or
      benefits of technology serving mankind].
AB  - The medical data processing has been introduced 10 years ago in the city hospital
      of Neuchatel. The application includes a problem oriented electronic medical
      record, software assistance for diagnoses coding, diagnostic and therapeutic
      files, access to Medline, specific applications for intensive care and
      neonatology, and also a medical server meant for exchanging data with general
      practitioners and other hospitals. The reliability, the security and the
      usefulness of the application are discussed, as well as the orientation of the
      new application, being developed at present, is described. The physicians, i.e.
      today users, must prepare themselves the applications for the coming years. The
      treatment of the medical data must be optimal and also make the personal
      relationship between the physician and his patient easier.

PMID- 8272721
TI  - [Anorexia!].

PMID- 8272722
TI  - [Which treatment can be proposed to a diabetic patient presenting with secondary
      failure of oral antidiabetics?].

PMID- 8272723
TI  - [Bucco-linguo-facial apraxia].

PMID- 8272724
TI  - [The Swiss Society of Internal Medicine changes its statutes--a change in
      convictions?].

PMID- 8272725
TI  - [Should Tolosa-Hunt syndrome still be an exclusion diagnosis?].
AB  - Since Hunt et al's description (1961) Tolosa-Hunt syndrome has been a matter of
      controversies about its nosological identity and differential diagnosis. We
      report 7 cases diagnosed between 1979 and 1990. Four of them had a low-resolution
      CT and the diagnosis was made after a long follow-up, according to classical
      criteria of exclusion. The last 3 cases had a modern high-resolution CT or a MRI
      (2 cases) and the diagnosis was established in a few days. MRI has considerably
      simplified the differential diagnosis but it has not completely resolved it.
      Alterations of shape and signal of the cavernous sinus are similar to those of
      lymphoma, sarcoidosis and meningioma. When MRI is normal diabetic
      ophthalmoplegia, migrainous ophthalmoplegia and giant-cell arteritis must also be
      considered. We conclude that the diagnosis of the Tolosa-Hunt syndrome can
      generally be made in a few days, without a cavernous sinus biopsy. There is no
      reason to doubt that this syndrome is a specific nosological entity.

PMID- 8272726
TI  - [Demyelinating involvement in Borrelian neuropathies].
AB  - Five patients (4 men, 1 woman, aged 51-67), were hospitalized for peripheral
      painful neuropathies. The serological survey and the dramatic responses to
      penicillin confirmed the responsibility of Borrelia burgdorferi in all 5 cases.
      Electromyographical studies showed evidence of demyelination: prolonged distal
      latency, slowing down of nerve conduction velocity. In 3 patients this pattern
      was related to axonal degeneration as shown by fibrillation potentials and
      reduced voluntary motor unit potentials recorded on needle examination. The other
      two showed no axonal degeneration. One also had motor conduction blocks. Such a
      demyelination could be due to vasculitis of the vasa nervorum described in tick
      bone meningoradiculitis.

PMID- 8272727
TI  - [Neurological form of cryptococcosis. Apropos of 2 atypical cases in non HIV
      infected patients].
AB  - Cryptococcal infection is the most common fungal infection of the central nervous
      system. More than 50% of the cases of cryptococcal infection are superimposed on
      an immunosuppressive or other general debilitating condition. Cerebral
      cryptococcosis usually presents as meningitis or meningoencephalitis, although
      cerebral granuloma has also been reported. Hydrocephalus is the most common
      neurosurgical complication of cerebral cryptococcosis. The majority of patients
      require only medical treatment with antifungal drugs. However, when complications
      ensue, surgical intervention is mandatory. We suggest that chronic meningitis be
      ruled out in all patients prior to the placement of shunts. In the two cases
      reported here treatment of cryptococcal meningitis was a combination of
      amphotericin B and flucytosine for six weeks. Fluconazole is a new alternative
      and at least as effective as amphotericin B.

PMID- 8272728
TI  - [Unconjugated pteridines and neuromeningeal infections].
AB  - Concentrations of unconjugated pteridines (neopterin, monapterin, biopterin,
      pterin) were measured in the cerebrospinal fluid (CSF) of 310 patients, using a
      high performance liquid chromatography (HPCL) method. Our cohort included 209
      controls (C), 15 patients with meningism (M), 22 with viral meningitis (VM), 17
      with bacterial meningitis (BM), 9 with herpetic meningoencephalitis (HME), 2 with
      tuberculous meningoencephalitis (TME) and 36 with peripheral systemic infections
      (PI). These measurements, expressed as nmol/litre, showed a gradation of
      neopterin concentrations according to the type of infection: 20.1 + 6.5 in group
      C; 46.9 +/- 29.9 in group PI; 274.3 +/- 231.7 in group VM; 699.2 +/- 711.2 in
      group BM, 1,101.9 +/- 1,107.9 in group HME and 1,169 +/- 1,171.9 in group TME.
      There was no such gradation with biopterin. Comparisons of means showed that
      total concentrations in the pathology groups were very different from those
      observed in controls and in the neuromeningeal infections of the PI group. There
      was no correlation between the number of lymphocytes and the concentrations of
      neopterin or biopterin in the CSF. It is concluded that the concentration of
      neopterin in the CSF is a sensitive but little specific marker of infection,
      independent of CSF cellular reaction. Measuring this concentration makes it
      possible: 1) to evaluate the status of immune defences; 2) to predict that a
      meningitis will become chronic, and 3) to detect a possible parenchymal
      participation in a meningeal infection.

PMID- 8272729
TI  - [Ischemic encephalopathy in primary antiphospholipid syndrome].
AB  - A 39-year-old man with livedo reticularis, optic neuropathy and acute ischemic
      encephalopathy (Sneddon's syndrome) had antiphospholipid antibodies. This primary
      antiphospholipid antibody syndrome was unsuccessfully treated by anticoagulation,
      corticosteroids and plasma exchanges. Despite a frank reduction of the
      circulating antibody titers after plasma exchanges, no improvement of the
      neurological symptoms was observed. Death was related to a systemic complication
      when the antibody titer was at its lowest level. This case provides further
      evidence that effective treatment for stroke associated with antiphospholipid
      antibodies is still wanting.

PMID- 8272730
TI  - [Incidents of brain tumors observed in the Grenoble area (canton of Meylan) 1979
      1990].
AB  - A high excess of risk (standardized incidence ratio S.I.R.: 320 [190-490]) of
      intracranial tumors among men living within the county of Meylan, in the suburb
      area of Grenoble, as compared with the overall population was shown by the Isere
      Cancer Registry, for the period 1979-1984. There has been no change of this
      excess of risk between 1979 and 1990 (S.I.R. = 190). The pathological homogeneity
      of this cluster (neuroglial tumors) among men is noticeable. This county is known
      as a concentration of high-tech and intellectual professional activities. A
      descriptive study was conducted on the 24 cases diagnosed between 1979 and 1990,
      based on retrospective interviews of patient's family. Ethnical origins, blood
      groups, personal and familial medical history (with special interest in cranial
      injuries), socio economic status, chemicals, radiations and electro-magnetic
      exposures, acoustic and visual exposures (such as noises and T.V.), drinking
      water, tobacco and food consumptions, were investigated. Educational level,
      occupation, and European ethnic origin are all pointing to the same direction: a
      higher risk in high level social classes and high level professions. An
      analytical study is going on, that would give a deeper insight in these
      phenomenons.

PMID- 8272731
TI  - [Central pontine myelinolysis with cerebellar ataxia and dystonia].
AB  - A 46-year-old alcoholic woman presented with dementia, chronic cerebellar ataxia
      and diffuse dystonia. Neurological examination also demonstrated emotional
      lability and a pyramidal signs on the four limbs. CT showed mild cerebellar and
      frontal atrophy. The diagnosis of central pontine myelinolysis was confirmed by
      MRI. The centropontine lesion gave an hyposignal on T1-weighted sequences and a
      hypersignal on T2-weighted sequences. It was shaped as a trident and symmetrical,
      sparing the tegmentum and the ventro-lateral regions of the pons. Cerebellar
      ataxia was related to cerebellar atrophy and extension of myelinolysis to the
      middle cerebellar peduncles. Dystonia, rarely reported in central pontine
      myelinolysis, was not associated with striatal lesions on MRI. The
      pathophysiology of these movement disorders in central pontine myelinolysis
      remains unclear. This case shows that central pontine myelinolysis is a rare
      cause of dystonia and can be diagnosed by MRI.

PMID- 8272732
TI  - [Functional hemispheric arousal and egocentric reference. An experimental study
      in 20 normal subjects].
AB  - The aim of this study was to evaluate the influence of each hemispheric
      functional arousal (right or left) on the designation of a subjective egocentric
      reference. The subjective designation of a egocentric reference was measured and
      compared in 20 right-handers healthy volunteers in cognitive tasks concerning
      either the right or the left hemisphere. The location of the egocentric reference
      was different during right or left hemispheric arousal. The hemispheric arousal
      induce a displacement of the egocentric reference to the contralateral space.
      These results are compared with clinical and neurophysiological studies and
      suggest new explorations to the mechanisms of heminegligence.

PMID- 8272733
TI  - [Association of amyotrophic lateral sclerosis and multiple sclerosis].
AB  - A twenty-five year old woman developed a progressive right hemiparesis which
      remitted within three months, without treatment. The diagnosis was a first
      relapse of multiple sclerosis. After a 10 year fully asymptomatic period, the
      patient developed weakness of the legs with falls and swallowing difficulties.
      Fasciculations and amyotrophy were present in the limbs and the tongue. There
      were no sensory abnormalities. The electromyogram confirmed the peripheral
      neurogenic degeneration with signs of anterior horn involvement. Motor and
      sensory nerve conductions were normal. Muscle weakness and atrophy increased in
      the limbs and the bulbar territory and the patient died nine months later. The
      autopsy showed characteristic "old" plaques of multiple sclerosis in the cerebrum
      with anterior horn cell and pyramidal tracts degeneration, typical of amyotrophic
      lateral sclerosis, in the spinal cord. Although exceptional, this association of
      amyotrophic lateral sclerosis and multiple sclerosis leads to the discussion of
      an etiological immunological dysregulation common to these two diseases.

PMID- 8272734
TI  - [Jugular foramen syndrome caused by herpes zoster].
AB  - Multiple cranial nerve palsies frequently occur in patients with cephalic zoster.
      Nevertheless, to our knowledge, involvement of the glossopharyngeal (IXth), vagus
      (Xth) and accessory (XIth) nerves has not yet been reported. We report a case of
      jugular foramen syndrome with palatolaryngeal herpetic eruption, aseptic
      meningitis and a high level of serum antibody to varicella-zoster virus.

PMID- 8272735
TI  - [Post-traumatic syringomyelobulbia and inferior vertical nystagmus].
AB  - A case of post-traumatic cervico-thoracic syringomyelia was complicated, 3 years
      after the injury, by a bulbar extension manifested by a downbeat vertical
      nystagmus which became a source of disabling oscillopsia. The syringobulbia was
      visualized at MRI. The usefulness of syringostomy in such a case is discussed.

PMID- 8272736
TI  - [Neuropathy caused by necrotizing vasculitis in HIV-1 infection].
AB  - A 33 year-old male homosexual infected with human immunodeficiency virus type I
      developed an asymmetrical and painful neuropathy in the lower limbs. Neuro
      muscular biopsy showed a necrotizing vasculitis. There were no clinical features
      indicative of systemic vasculitis. Prednisone therapy dramatically improved the
      neuropathy, without adverse effects. Although rare, necrotizing arteritis must be
      considered in HIV-1 patients with neuropathy, especially in case of
      mononeuropathy multiplex and when immunodepression is mild or absent, since a
      successful corticosteroid therapy can be prescribed.

PMID- 8272737
TI  - [Confrontation at the Salpetriere hospital. May 1991. Cephalalgia developing in
      depressive background and sudden death in a 26 year-old woman].

PMID- 8272738
TI  - [Cytological study of deep lung in spondyloarthritis. Apropos of 34 cases].
AB  - Bronchoalveolar lavage (BAL) was performed in 34 consecutive patients with
      spondyloarthropathy (SA) compared with 9 controls. Lymphocytic alveolitis was
      found in the SA group with decrease in the ratio of the CD4/CD8 subsets in both
      lung and blood. Neutrophilic alveolitis was also found in 5 patients with SA of
      long duration. As with other inflammatory diseases, it seems that a subclinical
      alveolitis is present in SA patients.

PMID- 8272739
TI  - [Pneumoblastoma. Apropos of a case].
AB  - The authors report a case of pulmonary blastoma, a rare type of pulmonary
      malignant tumour. The patient was treated by pneumonectomy combined with
      chemotherapy and radiotherapy. The outcome was favourable, and during an 11-year
      follow-up there was no sign of recurrence.

PMID- 8272740
TI  - [Radiological case: a developing nodule of the right lower lung].

PMID- 8272741
TI  - [Failure and success of pulmonary scintigraphy. Embolism has not said its last
      word...].

PMID- 8272742
TI  - [Apropos of the management of HIV-infected patients].

PMID- 8272743
TI  - [Synthesis of recommendations for the management of HIV-infected patients].

PMID- 8272744
TI  - [Treatment by antiviral drugs of HIV-infected patients].

PMID- 8272746
TI  - [Recommendations for the prevention of tuberculosis transmission in health care
      facilities].

PMID- 8272745
TI  - [Prophylaxis of opportunistic infections in HIV-infected patients].

PMID- 8272747
TI  - [Medical value of a respiratory mixture of oxygen and helium (Heliox)].
AB  - Lighter and more viscous than air, the oxygen-helium mixtures (heliox), well
      known to respiration physiologists, are used for functional exploration in the
      diagnosis of airways obstructions; they are also administered to deep-sea divers.
      However, it is usually little known that heliox can be used as therapeutic agent
      in the treatment of acute respiratory distress or severe disorders of ventilation
      caused by obstruction (e.g. inflammation). Heliox reduces the ventilatory work
      and increases alveolar ventilation, thereby improving haematosis and carbon
      dioxide elimination. The English-speaking authors, in particular, have a large
      experience of oxygen-helium mixtures in the treatment of such pathologies as
      severe asthma, small airways obstruction, cystic fibrosis, bronchoalveolitis,
      post-extubation pathologies, pharyngo-laryngeal oedema and drowning. The oxygen
      helium mixture, therefore, participates efficiently, simply and inaggressively in
      the treatment of airway obstruction and acute respiratory distress.

PMID- 8272748
TI  - CAD/CAM and its effect on the future of dental laboratory technology.

PMID- 8272749
TI  - Conversion of a conventional crown and bridge prosthesis to an implant supported
      restoration.

PMID- 8272750
TI  - Shortage of qualified dental technicians.

PMID- 8272751
TI  - Dental Laboratory Regulation: yes or no?

PMID- 8272752
TI  - The crown was beautiful--but!

PMID- 8272753
TI  - Determination of iron by the Ferrochem II: interference by tuberculostatics.
AB  - Iron levels in samples from certain treated tuberculous patients are
      underestimated by the Ferrochem II analyser. Of the tuberculostatic drugs
      examined for a possible interference, isoniazid, ethambutol, rifampicin,
      pyrazinamide and Rifater (a mixture of rifampicin, isoniazid and pyrazinamide),
      only pyrazinamide and Rifater (due to its pyrazinamide content) were associated
      with iron levels differing significantly (p < 0.001) from those of controls, with
      means of -317.2 and -185.6 mumol l-1 for pyrazinamide and Rifater respectively as
      against 9.91 mumol l-1 for the controls. The negative interference (I) due to
      pyrazinamide was independent of iron level in the samples but dependent on
      pyrazinamide concentration in the same (P) (r = 0.9993), I = -0.4380P-0.4276.

PMID- 8272755
TI  - A simplified method to determine galactose elimination capacity in patients with
      liver disease.
AB  - Galactose elimination capacity (GEC) is one of the most widely used liver
      function tests. It is relatively simple but still involves a number of capillary
      blood samples and is therefore fairly expensive. In the current study we present
      a simplified formula, based on GEC investigations in 103 cirrhotic patients, with
      which it is possible to estimate the GEC with one or two blood samples. Using
      this formula: GEC = [7.422--corrected B-galactose60 min]/4.575, we could
      accurately predict GEC in 24 additional patients.

PMID- 8272754
TI  - Haemostatic activation in patients with head injury with and without simultaneous
      multiple trauma.
AB  - In a prospective study including 16 patients with multiple trauma and head injury
      and 14 patients with isolated head injury we measured plasma levels of
      prothrombin fragment 1 and 2 (F1 + 2) and thrombin/antithrombin III complex (TAT)
      on admission and on days 1, 2, 3, and 7 after the incident. On admission, all
      patients had values of F1 + 2 and TAT above the reference range. Admission levels
      of both F1 + 2 and TAT were significantly higher compared with levels on the
      following days. Admission levels of F1 + 2 was significantly correlated to the
      Injury Severity Score. TAT was higher in patients with multiple trauma than in
      patients with isolated head injury and were significantly correlated to the
      Injury Severity Score on admission and on day 3. Levels of F1 + 2 were
      significantly lower on day 1 in four patients with post-traumatic pulmonary
      dysfunction compared with patients without pulmonary dysfunction. With respect to
      levels of TAT, no differences were detected between patients with and without
      pulmonary dysfunction.

PMID- 8272756
TI  - Diagnostic performance and prognostic value of serum troponin T in suspected
      acute myocardial infarction.
AB  - Cardiac troponin T (TnT) is a new serological marker for use as a diagnostic tool
      for myocardial damage. A blinded prospective multicentre study representing 298
      patients suspected of having acute myocardial infarction (AMI), and admitted to
      the coronary care units of six Scandinavian Hospitals was undertaken to assess
      the diagnostic performance and prognostic efficacy of a new cardiospecific TnT
      immunoassay. We used a discriminator TnT value of 0.20 microgram l-1. One hundred
      and fifty five patients (52%) had definite AMI, based on WHO criteria (all had
      peak S-TnT values of > or = 0.20 micrograms l-1); 127 patients (43%) had
      ischaemic heart disease (IHD) without AMI; and 16 patients (5%) had non-IHD (all
      had peak S-TnT values of < 0.20 microgram l-1). The 127 IHD-patients without
      definite AMI could be subdivided into a group of 44 patients with S-TnT peak
      values of > or = 0.20 microgram l-1, and a group of 83 patients with TnT below
      this level. An equal identification of these patients among the centres was seen
      (mean +/- SD 35 +/- 13%; range 20-55%). A follow-up study was able to define the
      clinical significance of these findings. The cumulative 6 months probability of
      suffering cardiac death or AMI was significantly higher in the subgroup with
      increased TnT values (14% (6/44)) as compared to the other subgroup (4% (3/83))
      (Log-rank test, p = 0.025). The probability of cardiac events was 15% for the
      patients with definite AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272757
TI  - Diagnostic accuracy evaluation using ROC curve analysis.
AB  - The diagnostic accuracy of a biochemical quantity is inversely related to the
      overlapping zone between the values of the population suffering from a disease
      and the population which does not. The ROC curves are an indirect measure of the
      overlapping zone between both populations. Specimens (plasma and urine) taken
      from 928 patients with symptoms of acute abdominal pain were used and the
      catalytic concentration of alpha-amylase, pancreatic alpha-amylase and
      triacylglycerol lipase (determined by two methods) were measured. Definitive
      diagnosis was obtained by following the directives of expert groups on the
      evaluation of diagnostic tests. Diagnostic accuracy was characterized by
      calculating the diagnostic sensitivity and specificity, by representing the ROC
      curves and by quantifying the areas under the ROC curves. The catalytic
      concentration of pancreatic alpha-amylase in plasma was the quantity with a
      greater area under the ROC curve (A = 0.9740) and then the one which had greatest
      diagnostic accuracy. If we considered the upper limit of the reference interval
      to be the cut-off value, the catalytic concentration of pancreatic alpha-amylase
      in plasma had a diagnostic sensitivity and specificity values of 0.96 and 0.88
      respectively for the acute pancreatitis.

PMID- 8272758
TI  - Rabbit lung macrophages stimulate platelets in vitro as observed by density
      gradient centrifugation and transmission electron microscopy.
AB  - Both platelets and macrophages play a role in the pathogenesis of
      atherosclerosis. To examine whether they may interact and, if they do, to
      elucidate the mechanisms of such an interaction, suspensions of the two cell
      types from rabbits were mixed together, then subjected to Stractan density
      gradient centrifugation and transmission electron microscopy. Suspensions of only
      one cell type served as controls. When otherwise unstimulated platelets and
      macrophages came into contact with each other, the platelets became less dense.
      Ultrastructurally, the platelets underwent shape changes without losing their
      granules, and were often arranged around the macrophages like a rosette. The
      processes of the macrophages became elongated. ADP caused a similar shift in
      platelet density and, when the cell types were together, increased this shift.
      With ADP the rosetting was abolished, but platelet aggregates were found to be in
      superficial contact with the macrophages. With thrombin the contact between the
      platelet aggregates and macrophages was close. Addition of platelet antagonists
      showed that the shift in platelet density and the rosetting upon contact with
      macrophages are dependent on divalent cations. Neither ADP, nor thrombin, nor PAF
      seem to be involved in the reactions.

PMID- 8272759
TI  - The cost of screening for hypercholesterolaemia--results from a clinical trial in
      Swedish primary health care.
AB  - The cost of screening for hypercholesterolaemia in a clinical trial was
      investigated at a primary health care centre. A convenience sample of the
      population was screened for inclusion in a study of the effectiveness of a lipid
      lowering programme. Included in the study were adults 30-59 years of age with a S
      Cholesterol of 6.50-7.79 mmol l-1 at randomization, plus two previous values > or
      = 6.50 mmol l-1 at screening and selection, with at least two other
      cardiovascular risk factors. In total 447 persons were screened and 37 were
      randomized into the lipid lowering programme. The mean cost per randomized person
      was estimated at about SEK 7500 (Swedish Crowns). An analysis of different
      inclusion criteria for treatment was also carried out. The cost of finding a
      patient to treat in the clinical trial was estimated to be more than three times
      as high with a total cholesterol cut-off point of 7.80 mmol l-1 compared with a
      cut-off point of 5.20 mmol l-1.

PMID- 8272760
TI  - Increased lipolytic activity of sera from pre-eclamptic women due to the presence
      of a lysophospholipase.
AB  - Sera from pre-eclamptic women exhibit an increased lipolytic activity compared to
      sera of women with normal pregnancies. The null hypothesis of this study was that
      the increased release of free fatty acids (FFA) was due to hydrolysis of
      circulating triglycerides. The nature of the increased lipolytic activity was
      investigated by incubating sera from pre-eclamptic (PE) and normal pregnant women
      (C) with various lipid substrates radiolabeled in the FFA position. The release
      of FFA in PE-sera was not due to hydrolysis of triglycerides or diglycerides.
      Lysophosphatidylcholine, however, served as substrate for the enhanced lipolytic
      activity. By using lysophosphatidylcholine with radiolabeled FFA in the sn-1
      position we found that 32 +/- 10 nmol FFA ml-1 h-1 was released in PE-sera,
      compared to 10 +/- 4 nmol FFA ml-1 h-1 in C-sera. This lysophospholipase activity
      appears independent of Ca2+ and other divalent cations. The increased release of
      FFA in sera of pre-eclamptic women can be explained by the presence of a
      lysophospholipase which releases the remaining fatty acid of
      lysophosphatidylcholine.

PMID- 8272761
TI  - Pre-operative plasma tetranectin as a prognostic marker in ovarian cancer
      patients.
AB  - Plasma tetranectin (TN) was tested as a biochemical prognostic marker in ovarian
      cancer on 39 patients. In stage I + II the 5-year survival was 33% (2/6) if
      plasma TN was < or = 6.7 mg l-1 and 100% (15/15) with plasma TN > 6.7 mg l-1. For
      stage III + IV the survival was 0% (0/11) at 26 months for patients with plasma
      TN < or = 6.7 mg l-1 and 29% (2/7) after 5 years with plasma TN > 6.7 mg l-1. By
      multivariate testing the relative hazard (RH) of death was found to be 73 times
      higher in patients with plasma TN < or = 6.7 mg l-1 compared to patients with
      values above 6.7 mg l-1 (p < 0.001). For comparison, the maximal RH for the other
      tested variables were: 15 for advanced stage, 2.5 for grade, four for residual
      tumour and 2.5 for younger age.

PMID- 8272762
TI  - Gender difference in red blood cell thiopurine methyltransferase activity.
AB  - High red blood cell (RBC) thiopurine methyltransferase (TPMT) activity is
      associated with a higher relapse rate in children with acute lymphoblastic
      leukaemia on 6-mercaptopurine therapy. RBC TPMT activity is subject to genetic
      polymorphism and inter-ethnic variation. Higher TPMT activity in male subjects
      has previously been reported in RBC and liver tissue, but only in non-healthy
      subjects. In this healthy, drug-free study group the gender difference in the RBC
      TPMT high activity subgroup was confirmed with 8.3% higher TPMT activity in male
      subjects (n = 105).

PMID- 8272763
TI  - Modelling of serial carcinoembryonic antigen changes in colorectal cancer.
AB  - Carcinoembryonic antigen (CEA) is a tumour marker mainly used for detection of
      recurrent colorectal cancer. CEA series in 295 patients, who had a macroscopic
      radical resection of a primary colorectal cancer were studied. A kinetic model
      was fitted to CEA series of individual patients. Applying the kinetic model
      recurrences were identified with a sensitivity of 70-80% and specificity of 80
      90%. Simulations were performed in order to find the optimal sampling strategy
      for CEA during follow-up. Simulations showed that CEA determinations at a few
      weeks interval between would be optimal for early detection of recurrences.

PMID- 8272764
TI  - Total protein in common duct bile measured by acetonitrile precipitation and a
      micro bicinchoninic acid (BCA) method.
AB  - Bile protein assays are complicated due to interference by other bile substances.
      In the present study we describe a microtiter plate method for the purification
      and quantification of bile proteins. The method is based on addition of
      acetonitrile in three steps to reconstituted freeze-dried bile, followed by
      ethanol washing of the precipitated proteins. Finally, protein in the precipitate
      is quantitated by two-point colour development using micro BCA reagents. Overall
      recoveries of protein in reconstituted bile spiked with exogenous protein
      (Seronorm) ranged from 91.0% (coefficient of variation; CV = 7.0%) to 97.1% (CV =
      2.4%) by recoveries of 125I-Fibrinogen and 125I-Albumin. Bile pigments were
      largely removed during precipitation and washing, as verified by high pressure
      liquid chromatography (HPLC). Preferably the samples should be freeze-dried
      initially, as this lowered the blank readings. Two-point colour development with
      the BCA reagents were identical for standards assayed directly and standards
      added to protein depleted bile, and processed through all steps. Hence, no
      interference by either residual bile constituents nor the reagents upon the BCA
      protein assay could be detected. Standard curves ranged from 0.05 to 5.0 gl-1 (r
      > 0.98). Within day reproducibility (n = 15) was 7.8% (CV) and day to day (n =
      10) was 12.1% (CV). Mean protein concentration in common duct bile from 30
      patients was 1.20 gl-1 (range 0.34-3.87 gl-1). The method appears suitable for
      assay of bile protein, requires only limited sample volumes and allows processing
      of many samples within a short time.

PMID- 8272765
TI  - Altered erythrocyte transmembrane transport of sodium and potassium in patients
      with conventional or reservoir ileostomy.
AB  - After proctocolectomy, the loss of the colonic absorptive capacity of sodium is
      compensated for by increased small intestine sodium absorption and renal
      conservation of Na by enhanced tubular reabsorption. These processes entail
      increased cellular sodium transport in the enterocytes and in the renal tubular
      cells. In order to evaluate if there is a general increase in cellular transport
      of Na after proctocolectomy for inflammatory bowel diseases erythrocyte Na and K
      contents and the transmembrane Na fluxes were determined in 35 patients with
      conventional ileostomy, 23 of which were reinvestigated after conversion to
      continent reservoir ileostomy. A selected group of another 12 patients having
      high output from their reservoir ileostomy and low urinary Na were studied
      concomitantly and 33 healthy subjects served as controls. The intracellular Na
      content did not differ between the groups while the intracellular K levels were
      higher in patients with conventional or continent ileostomy compared to controls.
      In addition, the Na influx and the efflux rate constant of Na were both increased
      after conversion to reservoir ileostomy. Na influx correlated positively with
      intake and urinary excretion of Na in conventional ileostomy patients. The
      results suggest that patients with ileostomy have an increased cellular K uptake
      and that construction of a reservoir ileostomy further alters cell cation
      transport by increasing the transmembrane Na turnover.

PMID- 8272766
TI  - The effects of venous blood, silicone gel and prilocaine on capsular contraction
      around silicone implants studied with a new method in the rat.
AB  - The pressure exerted by wound tissue on a subcutaneously implanted silicone
      expander was studied in rats. A significant increase in pressure was noted four
      and eight weeks postoperatively when venous blood was instilled into the cavity
      around the expander, but this increase was significantly reduced at eight weeks
      if 1.0 ml of prilocaine 5 mg/ml with adrenaline 4 micrograms/ml was instilled at
      the same time as the blood. Instillation of silicone gel outside the expander
      tended to increase the pressure eight weeks postoperatively, but there was no
      increase when silicone gel was given together with prilocaine and adrenaline. The
      next step is to investigate whether prilocaine with adrenaline instilled around
      an implanted mammary prosthesis in humans is not only capable of reducing pain
      and bleeding but can also inhibit capsular contracture.

PMID- 8272767
TI  - Changes in adrenergic nerves and tissue perfusion after freezing injury to the
      ear skin of rabbits.
AB  - The aim of the present study was to investigate by a combined trypan blue and
      catecholamine fluorescence technique the sequential changes in cutaneous
      adrenergic nerves, the distribution of blood flow, and vascular permeability at
      the demarcation line that occurred after experimental cold injury. Nine New
      Zealand white rabbits weighing 4.0-4.4 kg had frostbite induced by pressing the
      bottom of a glass bottle 2 cm in diameter filled with liquid nitrogen against the
      shaved skin of the ear. All the rabbits were anaesthetised with ketamine
      hydrochloride (Ketamine) and xylazine hydrochloride (Rompun). Specimens were
      taken one and three days, and two weeks after frostbite. Control samples were
      taken from the opposite normal ear. Trypan blue was injected into a saphenous
      vein just before the specimens were taken. The specimens were always taken in the
      same way and selected so that the probable demarcation line of the frostbite ran
      across the middle. The glyoxylic acid-induced fluorescence method was used to
      show the adrenergic nerves. There were no adrenergic nerves around the vessels
      and no arteriovenous anastomoses in the central area of the injury after one day,
      but catecholamines had started to accumulate in the adrenergic nerve endings at
      the margins of the injured area. This accumulation was still more obvious three
      days after frostbite. Some fluorescent regenerating adrenergic nerves could
      already be seen at the probable demarcation line two weeks after frostbite. There
      was increased trypan blue fluorescence near the margin of the injured area after
      one day, indicating extravasation and vascular damage.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8272768
TI  - A new partly external device for extension of skin before excision of skin
      defects.
AB  - Tissue expansion is a well established method for reconstructive surgery. As a
      complement, a new technique of skin extension has been developed, and tested
      clinically. The device consists of two holding bars with several straps placed
      between them, which usually is applied under local anaesthesia. It is an
      efficient, rapid, and inexpensive way of expanding skin before excision of skin
      defects. Thirty-two patients have been treated, three patients have had
      complications, and length of follow up ranged from 2-12 months.

PMID- 8272769
TI  - Nasal malformations associated with unilateral cleft lip. Accurate diagnosis and
      management.
AB  - The results of correction of nasal defects in patients with unilateral cleft lip
      are often disappointing because the malformation has not been clearly understood.
      Many illustrations of deformity of the lower lateral cartilage are anatomically
      incorrect. To understand the true nature of the deformity, the surgeon must have
      a fundamental knowledge of the musculature of the region, particularly the
      nasolabial portion of the orbicular muscle and the nasal muscle complex.
      Correction of the nose must establish a physiological nasal airway, which is
      necessary for good subsequent facial growth. This can be accomplished without
      either excessive scarring or a cartilage graft, by careful reconstruction of
      nasolabial muscular integrity with the anterior nasal spine and the
      septopremaxillary ligament, functional repair of the orbicular muscle, and
      finally by raising and rotating the displaced alar cartilage. These principles
      apply equally to both primary and secondary operations.

PMID- 8272770
TI  - Oronasal fistulas in cleft palate patients and their influence on speech.
AB  - The size, site, and influence on speech of oronasal fistulas were studied in 12
      patients with unilateral and 32 with bilateral cleft lip and palate. There were
      more and larger fistulas in the bilateral group. The series was divided into:
      those with fistulas that affected speech (group A, n = 18) and those with
      fistulas that did not affect their speech (group B, n = 26). Group A had
      significantly larger fistulas than group B, but there were no differences in the
      sites of the fistulas, either between the bilateral and unilateral groups or
      between groups A and B. Most fistulas were located in the region of the incisive
      foramen or in the hard palate. Judgements by listeners and analyses by the NORAM
      instrument were made of the speech of 12 of the patients in group A before and
      after temporary covering of the fistulas. Significant differences in
      hypernasality, according to both listener's judgments and instrumental analyses
      were found. This finding is further evidence that an oronasal fistula can
      influence and contribute to velopharyngeal dysfunction.

PMID- 8272771
TI  - Surgical treatment of developmental asymmetry of the breast. Long term results.
AB  - To evaluate our operative techniques for the treatment of breast asymmetry, 30
      patients were interviewed and examined three to 16 years after correction of
      developmental asymmetry. Breast symmetry was assessed by linear measurements and
      by subjective evaluation. The most satisfactory long term results were found in
      the patients who had undergone bilateral reduction mammaplasty or unilateral
      reduction mammaplasty combined with a contralateral mastopexy. In some cases
      longer lasting symmetry could be achieved by operating on both breasts using
      similar techniques. Long term results were not significantly better in those
      patients who had been operated after reaching the age of 18 years, compared with
      those of patients operated on at the age of 17 years or younger. To avoid
      psychological consequences therefore it is not always justifiable to delay
      operation until the breasts have matured.

PMID- 8272772
TI  - Neurophysiological investigation of hands damaged by vibration: comparison with
      idiopathic carpal tunnel syndrome.
AB  - Forty-seven men with numbness and paresthesiae in their hands after long-term
      occupational exposure to vibrating hand-held tools were examined
      neurophysiologically and clinically. The vibration thresholds of the finger tips
      were assessed and fractionated neurography of the median nerve motor and sensory
      fibres carried out. They were compared with control groups of healthy subjects
      and patients with idiopathic carpal tunnel syndrome. The patients exposed to
      vibration had major increases in their finger vibration thresholds, shown with
      both the Goldberg-Lindblom vibrameter and the Lundborg vibrogram. They also had a
      moderately increased motor distal latency at the wrist, but significantly less
      than patients with idiopathic carpal tunnel syndrome. Similar changes were seen
      in the sensory conduction velocities from finger to wrist. Measurement of
      fractionated conduction velocity across the carpal tunnel showed a bimodal
      distribution; one group of patients exposed to vibration had a significant
      reduction in conduction velocity similar to that in the genuine carpal tunnel
      syndrome, and one group had no localised affection at the carpal tunnel,
      suggesting more distal dysfunction at the level of palm or finger, or at the
      receptor level. A careful neurophysiological assessment of these cases is
      necessary before treatment is planned. It is particularly important to confirm
      median nerve damage at the wrist level if the carpal tunnel ligament is to be
      sectioned.

PMID- 8272773
TI  - Replacement of the os trapezium by polyurethane implants.
AB  - Twenty-five patients with arthrosis of the first carpometacarpal joint had the os
      trapezium replaced by a polyurethane implant (Tecoflex), and the results were
      evaluated after three years (range 28-47 months). There were three failures in
      which the implants had been removed because of dislocation with pain. The
      clinical results in the remaining 22 cases in terms of relief of pain and thumb
      function were comparable with previous series of silicone implants. Radiographic
      examination showed no signs of bone resorption or other unfavourable tissue
      reactions around the implants, but subluxation of the implants was seen in half
      of the cases. Implant subluxation might be caused by poor design of the implant
      or the limited amount of fibrous foreign-body reaction around the polyurethane
      material that resulted in less firm encapsulation than occurred around silicone
      implants.

PMID- 8272774
TI  - Treatment of large congenital naevi. A review and report of six cases.
AB  - To minimize the significant risk of early malignancy, and to obtain acceptable
      cosmetic results we have treated five infants with large congenital naevi by full
      thickness resection of the thickest part and superficial excision of the
      remaining parts of the naevus. The treatment was followed by rapid healing with
      little pigmented skin and minimal scarring. One patient treated at the age of six
      years showed a less favourable cosmetic result. Our experience confirms that the
      major part of the potentially malignant tissue can be removed and a greatly
      improved appearance achieved by early surgery. Additional surgery is usually
      necessary and should be completed before school age to prevent permanent
      psychological and social effects. Large congenital naevi are rare and difficult
      to treat. Their treatment should be centralised to regional hospitals that serve
      large populations.

PMID- 8272775
TI  - Double dislocation of the interphalangeal joints in the finger. Case report and
      review of publications.
AB  - A 66-year-old woman presented with a painful swollen finger and was shown
      radiographically to have dorsal dislocation of both interphalangeal joints, which
      responded to immobilisation and physiotherapy. Unlike single dislocations of
      finger joints double dislocations are rare, only 52 cases have been reported
      between 1874 and 1992 to our knowledge.

PMID- 8272776
TI  - Chronic erosion of a digit caused by a ring. Case report.
AB  - A 36-year-old woman had worn a small ring all the time since she was 5 years old.
      The ring caused chronic erosion through skin, extensor tendon, and most of the
      bone of the fourth digit of the right hand. The ring caused an infection and was
      removed; two years later the eroded bone had healed but she had a persistent
      extension contracture of the proximal interphalangeal joint.

PMID- 8272777
TI  - [Role of radiology in the diagnosis of aortic dissection].
AB  - Aortic dissection requires a prompt diagnosis and must be treated without delay
      in order to reduce the mortality rate. Whereas aortic dissection involving the
      ascending aorta (type A) requires immediate surgery, aortic dissection involving
      the descending aorta (type B) will usually be treated conservatively. This review
      article reevaluates the respective efficiency of conventional and modern
      radiological means offered in a well equipped university hospital.

PMID- 8272778
TI  - [Role of echocardiography in the diagnosis of aortic dissection].
AB  - Since the introduction of transesophageal transducers, Doppler echocardiography
      allows to detect aortic dissection with high sensitivity. The extent of the
      dissection can be determined accurately and the possibility of conducting the
      examination at bedside is particularly advantageous. Caution is advisable in
      interpreting doubtful observations in the distal part of the ascending aorta,
      which often ist incompletely visualized.

PMID- 8272779
TI  - [Clinical assessment of the patient with suspected dissecting aneurysm].
AB  - The clinical picture of aortic dissection is dominated by severe pain. In
      differential diagnosis the far more frequent acute myocardial infarction should
      chiefly be considered. Further evaluation is therefore only indicated when, in
      addition to pain, there are no signs of infarction in the ECG, additional aortic
      incompetence, pericardial effusion or history of hypertension. In recent years,
      in addition to contrast angiography, three non-invasive methods for this
      diagnosis have been developed: computer tomography, biplane esophageal
      echocardiography and magnetic resonance imaging. The sensitivity, specificity,
      advantages and disadvantages of these four methods are compared. In the
      individual center, according to the availability and expertise of the
      investigators, one method should be used as the first diagnostic tool. Only in a
      minority of patients should a second method be necessary until the diagnosis is
      confirmed or excluded, as is shown in our own series. A limitation to one, and in
      difficult situations possibly two, methods is not only important from the
      economic point of view but also to save time, since in aortic type A dissection
      surgery should be performed without delay.

PMID- 8272780
TI  - [Long-term treatment of patients with dissection of the thoracic aorta].
AB  - Thoracic aortic dissection is an extremely serious vascular accident which must
      be treated immediately. While ascending aortic dissection requires surgery as
      soon as possible, descending aortic dissection is only treated surgically when
      complications such as aortic ectasia, hemorrhage or ischemia occur. Late
      complications most often lead either to the patient's death or to reoperation.
      Late death occurs in 4-6% patients/year and about 3% patients/year undergo late
      reoperation. In our own experience these figures amount to 2 and 0.8%
      respectively.

PMID- 8272781
TI  - [Congenital heart defects--what happens in childhood?].

PMID- 8272782
TI  - Reparative cardiac surgery in the very young.
AB  - In addition to primary circulatory disturbance, the presence of congenital heart
      disease may compromise the development of organ systems including the myocardium,
      the pulmonary vasculature and the central nervous system. Therefore, early
      elective repair of complex congenital heart defects is desirable. Today repair of
      complex congenital heart defects in the neonate can be achieved at low early and
      late mortality and morbidity with favorable long-term functional results.
      However, much remains to be learnt about the cellular and molecular effects of
      open heart surgery and hypothermia on the neonate.

PMID- 8272783
TI  - [Interventional catheter therapy in childhood].
AB  - The paediatric therapeutic heart catheterization becomes more and more important
      in the treatment of congenital heart disease. Depending on the situation,
      interventional therapy can become an alternative or a replacement or supplement
      to surgical intervention. The methods of interventional therapy include the
      balloon valvuloplasty of stenotic valves or vessels, the implantation of stents
      and the occlusion of defects as well as of unwanted vascular structures with coil
      embolisation or umbrella devices. The balloon valvuloplasty of pulmonary valve
      stenosis or the embolisation of small vessels have become the treatment of
      choice. Valvuloplasty of aortic stenosis, angioplasty of residual coarctation,
      balloon dilatation of peripheral pulmonic stenosis and occlusion of a patent
      ductus arteriosus with a Rashkind PDA-occluder are now a valuable alternative to
      surgical procedure although studies of long-term results are not yet available.
      Occlusions of atrial or ventricular septal defects as well as the implantation of
      stents are still investigational tools, but give enormous hope for the future.

PMID- 8272784
TI  - Congenital heart disease in the adult: problems for the adult cardiologist.
AB  - Adult congenital heart patients form a growing group of patients. General
      principles of diagnostic and therapeutic needs in this group are discussed
      including the special organizational requirements for this new medical community.

PMID- 8272785
TI  - [Arrhythmias in the adolescent and adult with a congenital heart defect].
AB  - Rhythm disturbances may be observed in the natural history of congenital heart
      defects, as well as after open heart surgery. About 40-50% of adults with
      congenital heart defects will experience some type of arrhythmia. In the growing
      population of postoperative patients, the type of rhythm disturbance depends on
      the type of heart surgery: after operation at ventricular level, conduction
      disturbances and ventricular arrhythmias are quite common. After surgery at
      atrial level (e.g. closure of ASD, but much more after atrial correction of
      transposition), sick sinus syndrome and supraventricular arrhythmias are chiefly
      observed. Conduction disturbances may be subdivided into the very common
      intraventricular conduction defects (right bundle branch block, sometimes with
      left anterior hemiblock) and complete A-V block. Complete heart block has become
      less frequent in recent years since surgeons have learnt to avoid the bundle of
      His during VSD closure. All patients with postoperative complete heart block need
      a permanent pacemaker. Ventricular arrhythmias after ventricular surgery are
      commonly found if Holter recordings are done, particularly after correction of
      tetralogy. They are often asymptomatic but may be a cause of late sudden death (1
      3% of patients operated on for tetralogy). Antiarrhythmic treatment is indicated
      if symptoms are present, or in selected asymptomatic patients with a poor
      hemodynamic result (severe residual pulmonary stenosis or ventricular
      dysfunction). Sinus node dysfunction and sick sinus syndrome are common after
      atrial repair of transposition (Mustard or Senning operation). The manifestations
      are either sinus bradycardia and sinus arrest with long pauses, or atrial reentry
      tachycardia (Flutter); these may combine, so that antiarrhythmic medication must
      be associated with permanent pacemaker implantation.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8272786
TI  - [The antiphospholipid syndrome: fact or fancy?].

PMID- 8272787
TI  - [Antiphospholipid syndrome: a new clinical entity? Part 1: antiphospholipid
      antibodies: specificity and methodological problems].
AB  - A new clinical entity, the antiphospholipid syndrome, has recently been
      described. It is based on the detection of antiphospholipid antibodies either by
      coagulation tests or by ELISA assay. The precise epitopes towards which these
      antibodies are directed is a matter of controversy. It is even possible that the
      name antiphospholipid is inappropriate. The diagnosis of lupus like anticoagulant
      (LA) detected by coagulation tests requires a three step procedure after
      appropriate processing of plasma samples. Antiphospholipid antibodies can also be
      identified by ELISA; this assay is simpler, but there is still a need for
      standardization. LA and antiphospholipid antibodies identified by ELISA are
      similar, but not identical; they have similar clinical implications. Due to the
      heterogeneity of the antibodies and the antigens it is necessary to use a panel
      of tests to establish or exclude the presence of antiphospholipid antibodies. In
      the future a better knowledge of antibodies' specificity should help in selecting
      the most useful test for clinical purposes.

PMID- 8272788
TI  - [Antiphospholipid syndrome: a new clinical entity? Part 2: pathophysiological
      aspects and treatment possibilities].
AB  - Antiphospholipid antibodies are immunoglobulins of the IgG, IgM or rarely IgA
      class directed against phospholipids or phospholipid-protein complexes of the
      coagulation cascade. They were first described in patients with systemic lupus
      erythematosus, but are also frequent in other autoimmune diseases,
      lymphoproliferative and malignant disorders, some bacterial and viral infections,
      and after drug exposure. Their mechanism of action is considered multiple,
      disturbing various natural inhibitory pathways of coagulation. Clinically they
      have been associated with a thrombotic tendency without a proven direct causal
      role. Both arterial and venous thromboses, as well as habitual abortion in
      pregnant women, are reported. A variety of treatment measures have been tried
      against these associated clinical manifestations.

PMID- 8272789
TI  - [CT-guided percutaneous puncture-biopsy of the spine. Review of 104 cases].
AB  - Percutaneous biopsies (PB) of the spine under CT guidance have become an
      important diagnostic tool in managing tumoral or infectious disease of the spine.
      This retrospective review reports the results of 104 biopsies of the spine,
      except the cervical spine, performed in 98 patients (66 females and 55 males),
      aged from 3 to 92 years, without complications. The overall accuracy is 71% but
      it must be emphasized that the diagnostic accuracy in tumoral lesions is 100%
      whereas in the case of suspected infectious lesions the accuracy falls to 61.5%.
      Our view is that the negative results are independent of the technique and we
      propose a second biopsy before considering a surgical approach. We conclude that
      this technique is safe, accurate and easy to perform, not only due to the
      advantages of CT but also to the improvement in biopsy needles and
      histocytological techniques.

PMID- 8272790
TI  - [Lead poisoning following administration of "home specialties"].
AB  - Three cases of lead intoxication after the administration of "house specialties"
      are illustrated. The lead source could be traced to a lead-containing ointment in
      all three patients. Two of them suffered lead intoxication as a result of topical
      application to the lips, while the third had ingested the ointment orally.
      Clinical signs, diagnosis and therapy of lead poisoning are described in the
      light of the case reports. The patients were treated with various drugs (N
      acetylcysteine and the complex chelators D-penicillamine and 2.3
      dimercaptosuccinic acid (2.3-DMSA). The therapeutic effects were determined on
      specific laboratory features in blood and urine. N-acetylcysteine was not
      absolutely confirming in our case. D-penicillamine was effective, but only after
      removal of the source of exposure. Because of its known adverse drug reactions,
      we preferred the oral lead chelator 2.3-DMSA. Treatment with DMSA resulted in a
      considerable decrease in the blood lead concentration and in increase in urinary
      lead output. The urinary excretion of aminolevulinic acid and coproporphyrin
      normalized under DMSA. The treatment was well tolerated and no appreciable side
      effects were noticed. The literature on metabolism and the characteristic effects
      of lead intoxication is reviewed and the production, qualities and administration
      of emplastrum plumbi are described. All three lead-containing ointments are
      summarized by the characterizing term "house specialties". One wonders whether it
      is justified that there is still control and registration of such "house
      specialties" in Switzerland.

PMID- 8272791
TI  - [Internal medicine at the crossroads].

PMID- 8272792
TI  - The role of internal medicine and its specialties research, education and patient
      care.

PMID- 8272793
TI  - Fluor in the treatment of osteoporosis. An overview of thirty years clinical
      research.
AB  - It has long been known that fluoride "hardens" mineralized tissues. Fluoride
      ingestion through drinking water in areas naturally rich in fluoride leads to
      osteosclerosis, known as endemic fluorosis. The first suggestion that fluoride be
      used in the treatment of osteoporosis was made in 1964. However, despite 30 years
      of research, the treatment remains controversial. Fluoride has a dual effect on
      osteoblasts. On the one hand, it increases the birthrate of osteoblasts at tissue
      level by a mitogenic effect on precursors of osteoblasts, while on the other hand
      it has a toxic effect on the individual cell with mineralization impairment and
      reduced apposition rate resembling osteomalacia. Fluoride has a positive effect
      on axial bone density, but the axial bone gain is not matched by similar changes
      in cortical bone. Furthermore, approximately one third of patients are non
      responders. The effect of the addition of fluoride to the drinking water on
      fracture rate is not clear. It probably only has a small relative impact on total
      hip fracture rates. In two controlled fluoride therapy studies the incidence of
      vertebral fractures decreased, while in two other studies it increased.
      Experience teaches that denser bones are not necessarily better bones. The major
      side effects of fluor therapy are skeletal fluorosis, gastrointestinal
      intolerance, and painful lower extremity syndrome. Fluoride is the single most
      effective agent for increasing axial bone volume in the osteoporotic skeleton;
      however, its therapeutic window is narrow. The best candidates for fluoride
      therapy are patients with axial osteoporosis but with good peripheral bone
      density. They should have a good renal function and vitamin D status.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8272794
TI  - [Current treatment concepts in primary osteoporosis: calcitonin].
AB  - The beneficial effect of calcitonin treatment on osteoporosis is generally
      accepted. Analgetic potency and inhibition of osteoclasts are well documented for
      both the injectable and the nasally applicable hormone. Preventive and
      therapeutic long-term application is followed by a significant increase in bone
      density at different axial and peripheral sites of the skeleton both in
      postmenopausal and in corticoid-induced osteoporosis. According to recent data
      these increases run parallel to a decrease in fracture incidence. When treating
      patients with calcitonin, different aspects must be taken into consideration,
      some of which need further clinical investigation. Patients with high-turnover
      osteoporosis generally show a better response to therapy. Data concerning the
      advantages and disadvantages of different calcitonins are lacking. Most clinical
      studies were done with salmon calcitonin. The lowest effective dosage of
      subcutaneously or nasally administered hormone should be further investigated.
      Secondary resistance after long-term use may be avoided by intermittent
      administration. An optimal schedule concerning treatment and free intervals has
      to be determined. A schedule with three months on an three months off is at
      present proposed by different groups. Combination with calcium can be
      recommended. Continuous or cyclical combinations with other drugs are under
      investigations.

PMID- 8272795
TI  - [Duality of the analgesic effect of tramadol in humans].
AB  - Tramadol is a central analgesic with low affinity for opioid receptors. A major
      active metabolite (O-desmethyl-tramadol) shows a higher affinity for opioid
      receptors than tramadol. The influence of naloxone and quinidine (a selective
      P450DB1 or CAP2D6 inhibitor) on tramadol effect was investigated crossover and
      double-blind vs placebo in healthy subjects. They received tramadol (100 mg
      p.o.), tramadol+naloxone (0.8 mg i.v.) and tramadol+quinidine (50 mg p.o.).
      Analgesia was assessed, after transcutaneous electrical stimulation, by a
      categorical numerical scale and by measurement of the antinociceptive effect at
      spinal level by R-III reflex. Analgesia peaked at 3 hours and lasted about 6
      hours. The mean decrease in peak tramadol analgesia by naloxone was only 31%.
      Quinidine had no effect on the extent of tramadol analgesia, but inhibited
      tramadol induced myosis. We therefore conclude that tramadol analgesia is only
      partially mediated by a mu opioid agonist effect. Tramadol analgesia thus results
      from an action on opioid receptors other than the mu subtype and/or from
      nonopioid effects (monoaminergic system). Quinidine blockade of tramadol myosis
      suggests that the mu agonist component of tramadol effect results from its O
      demethylation by the polymorphic P450DB1 enzyme.

PMID- 8272796
TI  - [Mycoplasma hominis empyema following pleuropneumonia in late pregnancy].
AB  - Mycoplasma hominis (M. hominis) frequently colonizes the genital tract, but is
      rarely isolated from the respiratory tract. Dissemination of M. hominis has been
      documented in women with a febrile illness after delivery. Spontaneous recovery
      is the rule. A 32-year-old woman in the 29th week of pregnancy was hospitalized
      for pneumonia. She had to be ventilated for respiratory insufficiency and
      thoracic empyema. The child was delivered by section due to signs of stress in
      cardiotocography. In the ensuing days the mother's condition worsened, with
      fever, weight loss and persistent pleural effusion. Even after decortication and
      treatment with ceftriaxone fever and pleural effusion persisted. M. hominis was
      found in pleural fluid cultures. Treatment with doxycycline led to rapid
      defervescence and an improvement of the patient's condition.

PMID- 8272797
TI  - [Prevalence of diabetes in Switzerland: calculation based on drug sales].
AB  - Data on prevalence of diabetes mellitus in Switzerland are scarce. In connection
      with a EURODIAB project the prevalence of diabetes was assessed in a standardized
      form, based on sales data for antidiabetic drugs. The prevalence of diabetes
      treated by specific drugs was calculated on the basis of Swiss sales data for
      antidiabetic drugs (corrected for combination therapies), the average prescribed
      daily dosages of insulin and oral antidiabetic drugs (OAD) defined by an inquiry
      in 38 pharmacies, and the mean annual population of Switzerland. The following
      prevalence rates were obtained (patients per 1000 inhabitants): [table: see text]
      Prevalence data obtained by the same, standardized method are higher in France
      (1.3%), Belgium (1.64%), Sweden (1.7%), and much higher in Italy (2.2%).
      Calculation based on drug sales data is an easy method of obtaining prevalence
      rates of diabetes mellitus. In comparison with field studies, discompliance and
      non-inclusion of diabetics treated only with diet do admittedly lead to low
      prevalence rates. Nevertheless, the chosen method is very useful for longitudinal
      observations and for international comparisons.

PMID- 8272798
TI  - [Drug prices in Switzerland: European comparison of "comfort" drugs].
AB  - We compared the average Swiss prices of so-called "comfort medicines" with the
      prices operating in several other European countries. These drugs, which are
      numerous in Switzerland, were defined as having no demonstrable efficacy or as
      being prescribed for physiopathological entities of uncertain scientific basis.
      The comparison shows that the average price of comfort medicines in Switzerland
      is not different from the German price (-17%, ns), but is higher than in Sweden
      (+35%, p < 0.05), France (+61%, p < 0.01) and Italy (+65%, p < 0.01).
      Furthermore, the average price of innovative new chemical entities is strongly
      correlated with that of the comfort medicines in all the countries considered and
      despite the vastly different therapeutic value of these two categories of drugs.

PMID- 8272799
TI  - [Pretransplant activity of cytotoxic T-lymphocytes in non-related bone marrow
      donor/recipient combinations with a perfect HLA match].

PMID- 8272800
TI  - [A new method of HLA-DR typing using molecular biology: 1-year experience in bone
      marrow transplantation].

PMID- 8272801
TI  - [Direct genetic diagnosis in Huntington's chorea].
AB  - Huntington's disease is a late manifesting autosomal dominant neurodegenerative
      disorder. It is characterized by motor disturbance, loss of cognitive functions
      and psychiatric manifestations. Recently, the disease causing mutation, an
      unstable DNA sequence in the coding region of the Huntington gene on chromosome
      4p, has been identified. A trinucleotide (CAG) repeat is expanded over the normal
      range and can easily be detected by standard laboratory methods. Accurate genetic
      testing can now be offered in clinically questionable cases and to subjects at
      risk for Huntington's disease. Furthermore, there seems to be a correlation
      between the size of the expanded CAG repeat and the age of onset in affected
      individuals. We have investigated more than 130 individuals from different
      affected families and illustrate the advantages and the clinical application of
      the new method.

PMID- 8272802
TI  - [Transient eosinophilia in primary biliary cirrhosis].
AB  - We reviewed 144 differential white blood cell counts from 23 patients with
      primary biliary cirrhosis (PBC, 21 females, 2 males) for occurrence of
      eosinophilia. Over an average observation time of 43 +/- 9 months, 9/23 (39%, 9
      female) patients were found to have transient absolute (> 500/mm3, n = 5) or
      relative (> or = 6%, n = 4) blood eosinophilia. The maximum value of eosinophilic
      granulocytes observed was 1385/mm3 (19%). Other causes of eosinophilia had been
      ruled out. Eosinophilia was transient, disappearing without treatment.
      Significantly younger patients with eosinophilia also had a tendency to
      prognostically more favourable values for serum albumin, prothrombin time,
      bilirubin and galactose elimination capacity. None had edema, compared to two
      patients with edema in the group without eosinophilia. Two patients died during
      the observation period; both were from the group without eosinophilia. The
      average 5- and 7-year survival probability, calculated on the Mayo survival
      model, tended to be higher for patients with eosinophilia (92% and 87%) compared
      to patients without eosinophilia (79% and 72%). In patients with eosinophilia,
      disease stage I (5/6 vs 1/9) and epitheloid cell granuloma (4/6 vs 1/9) were
      significantly more frequent. Blood eosinophilia in PBC seems to be an indicator
      of an early disease state with florid bile duct lesions. Primary biliary
      cirrhosis should therefore be considered--with other hepatopathies--as a possible
      cause of eosinophilia of otherwise unknown origin. These observations could be of
      importance for future therapeutic concepts, at least for patients in early
      disease states.

PMID- 8272803
TI  - [HIV prevention in HIV-positive drug addicts. A methadone-supported model].
AB  - In Switzerland, an estimated 15-25% of intravenous drug users (IVDUs) are
      infected with human immunodeficiency virus (HIV). It has been suggested that
      reduction of HIV-transmission-prone behavior could be achieved in so-called
      "early intervention programs". Few public prevention programs have so far been
      targeted to HIV-infected IVDUs. Socially marginalized, jobless, street-based, HIV
      infected IVDUs are those hardest to reach for education programs: it was the
      hypothesis that they can be motivated for HIV-prevention efforts by methadone
      based comprehensive social and medical care. The program was established by
      integrating one additional social worker in an outpatient clinic for infectious
      diseases in St. Gallen, a city with a population of 70,000 inhabitants in eastern
      Switzerland. Access to the 29 clients of this study (10 women, 19 men) was
      facilitated by offering methadone treatment (follow-up 5 to 29 months).
      Abstinence from additional illegal drugs was not required. Methadone, plus social
      care and medical treatment was provided by a small team consisting of a social
      worker, a physician and a nurse. A gradual approach was chosen to establish a
      working relationship with clients. The first attempt was to satisfy basic medical
      needs, housing, and financial support as well as to strengthen relevant personal
      relationships. Once trusting cooperation was established, reduction of
      transmission-prone behavior was targeted. The results show that social
      performance can be greatly improved by integrated social, psychological and
      medical assistance: for the 16 initially homeless housing was found, 14 found a
      job and for all but 2 basic financial support was eventually guaranteed. Self
      reported drug abuse was markedly reduced, as was transmission-prone behavior by
      prostitution, unsafe sex practices, needle sharing and improper disposal of used
      syringes. Breaking the isolation of socially marginalized IVDUs seems to be the
      important move to enhance their social responsibility as carriers of HIV.

PMID- 8272804
TI  - [Demonstration of intrathecal antibody formation against Borrelia burgdorferi in
      Lyme neuroborreliosis].
AB  - Neurologic complications are common in Lyme borreliosis. In adults in particular,
      detection of intrathecally formed antibodies to B. burgdorferi is a decisive
      diagnostic criterion. As in neurosyphilis diagnosis, the specific antibody titer
      against B. burgdorferi in the CSF is compared with the serum titer by calculating
      the specific antibody indices, taking into account the disturbed blood/CSF
      barrier. Deriving from these specific indices, we adapt by dilution the serum IgG
      level to that in the CSF of the same day, thus allowing for passive diffusion of
      antibody through the blood/CSF barrier. Determination of the specific antibody
      titer by indirect immunofluorescence demonstrates intrathecal synthesis of
      specific antibodies against B. burgdorferi if the CSF titer is higher than in the
      diluted serum tested in parallel. The individual methods are presented in a group
      of patients.

PMID- 8272805
TI  - [Splenectomy in unrecognized portal hypertension: a risky undertaking].

PMID- 8272807
TI  - [Micro-insemination--a novel treatment method for sterility in severe male
      subfertility].
AB  - Microinsemination is a new method of treating sterility. It improves the chance
      of fertilization in cases of severe male subfertility and of unexplained
      infertility. Fertilization is assisted by opening the zona pellucida with a
      microneedle (PZD), by introducing a small number of sperms with a micropipette
      into the perivitelline space (SUZI) or by direct insertion of a spermatozoon into
      the ooplasm (ICSI). We report on the first delivery achieved by microinsemination
      (SUZI) at the University Hospital Zurich and, as far as we know, in Switzerland.

PMID- 8272806
TI  - [Portal venous thrombosis following splenectomy in portal hypertension: risks and
      management].
AB  - Splenectomy intended to treat hypersplenism can, in the presence of portal
      hypertension (PTH), lead to extrahepatic portal and mesenteric vein thrombosis.
      The management of possible variceal bleeding in patients with extrahepatic portal
      vein occlusion following splenectomy in portal hypertension is a problematic and
      challenging undertaking. We report on the management of variceal bleeding in 2
      noncirrhotic patients with PTH who developed portal vein thrombosis following ill
      advised splenectomy. It must be stressed again that splenectomy alone intended to
      control hypersplenism in portal hypertension is to be avoided at all costs.
      Options for the treatment of portal and mesenteric vein thrombosis and variceal
      bleeding are proposed.

PMID- 8272808
TI  - [Psyche and immunity. A selected literature study of psychoneuroimmunology in
      healthy persons].
AB  - In the new field of psychoneuroimmunology essential ground has already been
      broken. Precisely in man, however, only hypotheses are possible in important
      areas: one that is commonly voiced is that stress weakens the immune system and
      would favour the onset of disease. A situation report is presented which
      summarizes, classifies and compares all 67 published studies relating psychic
      influences to immunologic factors in healthy human beings. A notable proportion
      turned out to be doubtful from the formal standpoint, e.g. no controls (40
      publications) or with fewer than 30 probands (19). In 13 of these studies
      neuroendocrinologic parameters were taken into account and in 14 biological
      (health/disease) parameters. 42 studies were based on "externally defined" stress
      situations (partner loss, examinations, care of severely ill family members,
      space shuttle mission, etc.), 16 on specific personality traits and 9 on
      experimental stress situations or relaxation efforts. Since the studies varied
      widely in design, psychic starting position, psychic assessment (91 different
      methods) and immunity (68 varying parameters) and also in regard to the
      biological result (various "endpoints" of health/disease), only a few general
      conclusions can be drawn. Subjective or objective stress can be associated with
      diminished lymphocyte functions such as reduced mitogen stimulation and natural
      killer cell activity, elevated antibody titers against some latent and/or
      ubiquitous viruses, and reduced immunoglobulin A in saliva. This is confirmed to
      varying degrees, usually on a shortterm basis and not in all studies. Others
      contain evidence that the immunologic changes mentioned may be associated with
      particular personality traits (anxiety, depression, loneliness, good coping,
      power motive syndrome, social support, etc.). What the immunologic changes had in
      common was that they moved within a relatively narrow range and overstepped the
      norm little or only marginally. Whether the immunologic "anomalies" observed
      reflect a weakened immune system or an adequate "homeostatic" immune modulation
      by psychic signals, or point to adequate immune defence in an altered "antigen
      situation" arising from a changed lifestyle in stress situations, cannot be said.
      There is little evidence of a relationship to disease onset. While the present
      review shows certain relationships between psychic and immunologic factors, their
      biological relevance remains unclear. The often voiced hypothesis that stress
      weakens the immune system and a larger number of diseases therefore ensue cannot
      be confirmed or denied by the available data. The results permit other,
      contradictory hypotheses.

PMID- 8272809
TI  - [Concerning: Briner V: Hypertensive crisis. Schweiz Med Wochenschr 1993; 123: 844
      852].

PMID- 8272810
TI  - [Therapy of resistant gram-positive infection: value of glycopeptide antibiotics
      vancomycin and teicoplanin].

PMID- 8272811
TI  - [Surgical laparoscopy in tumors of the adnexa].
AB  - OBJECTIVES: The laparoscopic management of adnexal masses is still controversial.
      The main problems are preoperative diagnosis, operative technique and the
      possibility of compromising the prognosis by spillage of cancer cells when
      operating on a hitherto unrecognized early stage ovarian cancer. We report on our
      experience with minimal invasive surgery of adnexal masses. METHOD: From June
      1989 to July 1992, 375 patients underwent surgery for adnexal tumors at the
      University Hospital, Zurich. In 112 cases a laparoscopic operation was performed.
      The indications were unilateral or bilateral masses in the adnexal region with or
      without clinical symptoms. The preoperative workup included patient's history,
      clinical examinations, vaginal sonography and intraoperative evaluation of the
      tumor. RESULTS: In 72% (83) of cases the organs were preserved by the
      laparoscopic procedure while in 28% (32) salpingo-oophorectomy, ovariectomy or
      salpingectomy was performed. The histopathologic findings included cystadenomas,
      cystadenofibromas, benign cystic teratomas, simple and functional cysts,
      mesothelium cysts, tubo-ovarian abscesses, endometriomas, and torqued tubes
      and/or ovaries. In no patient was a malignant process found. Only one
      postoperative complication was noted in a patient who had to be relaparoscoped
      due to adhesions to the operated ovary. One recurrence occurred in a
      hydrosalpinx. CONCLUSIONS: Adnexal masses may safely be managed laparoscopically,
      with all the advantages of minimal invasive surgery, provided that strict
      diagnostic and therapeutic rules are observed.

PMID- 8272812
TI  - [Seasonal variations in arterial pressure in hypertensive patients].
AB  - Blood pressure (BP) was measured once every month during one year in 80
      hypertensive outpatients. An orthostatic test was performed in winter and another
      during summer. The collective was aged 65 +/- 13 years (m +/- SD) and presented
      an elevated prevalence of diabetes mellitus, cardiac failure, and coronary,
      cerebral and arterial insufficiency. Diuretics, betablockers, converting enzyme
      inhibitors and calcium channel blockers were used by 31 patients as monotherapy
      and by 49 patients in association. During summer a significantly lower seated BP
      was found (144.1/79.4 mm Hg vs 150.8/82.9 mm Hg in winter, p < 0.001). One fourth
      of the patients did not show this diminution. On the basis of the WHO criteria of
      BP definition, 31% of the patients could be considered hypertensive in winter vs
      16% in summer and 28% as normotensive in winter vs 43% in summer (p < 0.05). The
      summer reduction in BP depended on position. It was less marked in seated
      position (-5.3/-2.7 mm Hg) than in lying (-6/-5.1 mm Hg) or even in standing
      position (-10.8/-5.1 mm Hg). The orthostatic test induced a greater immediate
      fall in systolic BP in summer than in winter (-14.4 vs -9.6 mm Hg, p < 0.001),
      more orthostatic hypotensive episodes defined as a systolic BP fall of 20 mm Hg
      or more (34% of patients vs 20% in winter, p = 0.05) and more signs of reduced
      cerebral perfusion (14% vs 7.5% in winter, NS). Diabetic patients and patients
      treated by diuretic and vasodilator drugs are particularly exposed to orthostatic
      hypotension in summer. Betablockers can minimize this risk.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8272813
TI  - [Brucellosis: case report and synopsis of 10 cases (1973-1992) in the Chur canton
      hospital].
AB  - A 33-year-old patient from former Yugoslavia presented with low back pain and
      fever. Plain X-rays and myelography were normal, but a technetium-99m scan was
      suspect for vertebral osteomyelitis. Serology and blood cultures were positive
      for Brucella (melitensis). Antibiotic therapy with tetracycline and rifampicine
      rapidly improved the signs and symptoms of the infection. A retrospective
      analysis of 11 cases of Brucellosis treated in the Kantonsspital, Chur, over the
      years 1973 to 1992 revealed that 9 patients were foreign workers from rural areas
      in the Mediterranean region (Spain, Portugal, Italy, Yugoslavia, Greece). The
      majority had a history of consuming milk and dairy products from their own farm
      animals up to a few months before the onset of symptoms. Blood cultures were
      positive in 5 cases (B. melitensis) while the remaining 6 had high titers of
      agglutinating antibodies. A diagnostic delay of several weeks to months was
      typical. Because Brucellosis usually presents with unspecific often flu-like
      symptoms, with unspecific laboratory findings, and with a varying array of organ
      manifestations a high index of suspicion is essential for a timely diagnosis.

PMID- 8272814
TI  - [Concerning: Gluck U: Is Chinese medicine reconcilable with our viewpoint?
      Schweiz Med Wochenschr 1993; 123: 1005-1012].

PMID- 8272815
TI  - [Abstracts of the 57th and 58th annual meetings of the Swiss Society for
      Gastroenterology and Hepatology. Lugano, 10-12 September 1992 and Interlaken, 23
      25 September 1993].

PMID- 8272816
TI  - Psychological aspects of ethical decision making.

PMID- 8272817
TI  - An analysis of the medical problems causing Medicaid patients to present at a
      community hospital emergency room.

PMID- 8272818
TI  - The musical instrument museum.

PMID- 8272820
TI  - Biological environmental specimen banking. Papers presented at the 1st
      International Symposium on Biological Environmental Specimen Banking, Vienna,
      Austria, 22-25 September 1991.

PMID- 8272819
TI  - Current activities within the National Biomonitoring Specimen Bank.
AB  - The National Institute of Standards and Technology (NIST) has been involved in
      biological environmental specimen banking activities since 1979. These
      activities, which are known collectively as the National Biomonitoring Specimen
      Bank (NBSB), include the banking of a variety of specimens (human liver,
      sediment, mussels/oysters, fish tissue and marine mammal tissues) from several
      different projects supported by different government agencies. The two most
      recent projects, the Alaska Marine Mammal Tissue Archival Project (AMMTAP) and
      the National Marine Mammal Tissue Bank (NMMTB), focus on the collection, banking
      and analysis of marine mammal tissues and they are part of a comprehensive plan
      to address marine mammal monitoring, specimen banking and quality assurance of
      analytical measurements associated with contaminant analyses in marine mammals.

PMID- 8272821
TI  - Canadian Human Specimen Bank: an emerging Great Lakes health effects program.
AB  - Plans for establishing a Canadian human specimen bank as part of the Great Lakes
      Health Effects program initiated by the Environmental Health Directorate, Health
      and Welfare Canada, have been under consideration since 1990. This presentation
      delineates the program rationale, our objectives in establishing the bank and the
      progress we have made to-date in achieving our goal. This paper is intended to be
      a planning document.

PMID- 8272822
TI  - Human organ specimen banking--15 years of experience.
AB  - As a reaction to the lack of information concerning ranges of a 'normal
      xenobiotic burden' within the population and also the aquatic, terrestrial and
      atmospheric environments, the sampling and storage of environmental materials in
      Germany in 1974 as a possible tool for environmental observation and early
      recognizing of hazards was proposed. During subsequent years the collection of
      human specimens was undertaken in Munster. In a pilot phase (1978-1983)
      conditions of optimized storage were investigated, including reliable storage
      temperature and container materials. Since 1985 the Environmental Specimen Bank
      for Human Tissue in Munster has been institutionalized under the auspices of the
      Federal Ministry of Environment, Nature Protection and Nuclear Safety as well as
      the Federal Environmental Agency in Berlin. Up to 1991 about 300,000 samples had
      been collected and stored at -85 degrees C in a walk-in deep-freezer of 34 m3
      comprising autopsy material as well as 'available' organs form living persons
      (e.g. blood, urine, hair, human milk, saliva, seminal plasma, sweat). Having
      fulfilled the tasks within the scope of environmental banking the Munster
      institution has proved to be an adequate scientific tool. It has been integrated
      into the logistic system of the Environmental Specimen Bank in Germany having the
      following main tasks (a) the development of Standard Operation Procedures (SOP)
      for sampling and sample handling, (b) evaluation of reliable analytical methods
      for inorganic and organic sample characterization, (c) collection of a sufficient
      data pool for reference ranges of xenobiotics, which are essential for
      environmental risk assessment, and (d) the evaluation of the efficacy of
      legislative xenobiotic restrictions: this could be proved for lead and some
      organochlorine pesticides.

PMID- 8272823
TI  - Implementation of specimen banking concepts in developing countries. First trial-
      Sri Lanka.
AB  - The necessity to establish a small scale Environmental Specimen Bank projects in
      tropical countries is stressed. An example from Sri Lanka demonstrates the needs,
      the benefits and the prospects of such an integrated research project.

PMID- 8272824
TI  - Biological environmental specimen banking in Slovakia.
AB  - Biological environmental specimens, including samples of human tissues, were
      stored for 5-10 years after solubilizing by mineralization in boiling nitric
      acid. The sampling procedure, transport treatment and storing was standardized.
      Documentation identifying the sample and its origin were used. Data on toxic
      metals in dust-fall, in the individual components of the environment as soil,
      air, ground and surface water, plants, animals, food and human tissues (liver,
      kidney, lung, brain, heart and plasma) are reported for the 6 most heavily
      contaminated regions of Slovakia. In some areas xenobiotics in the environment
      seriously affected the flora and fauna, including man. Banking of specimens has
      been stressed as the necessity for future analyses.

PMID- 8272825
TI  - The Swedish Environmental Specimen Bank with reference to the National
      Contaminant Monitoring Programme in Sweden.
AB  - The environmental Specimen Bank (ESB) at the Swedish Museum of Natural History
      constitutes the base for the National Contaminant Monitoring Programme in Sweden.
      This is a part of the Swedish Environmental Monitoring Programme (PMK). Since the
      beginning of the 1960s more than 120,000 organisms have been collected and stored
      in the Swedish ESB. The present PMK-programme started in 1978 under the authority
      of the Swedish Environmental Protection Agency. The present paper gives a brief
      presentation of main types of material and species annually collected for storage
      in the Swedish ESB, with special reference to the Contaminant Monitoring
      Programme.

PMID- 8272826
TI  - Biological specimen bank for smelter workers.
AB  - The biological specimen bank was initiated by the department of Environmental
      Medicine and the department of Medicine at the University of Umea in 1975. The
      aims of the bank are to collect information on trace elements in human organs.
      Special attention is focused on the influence of occupational exposure. Tissue
      samples are taken from deceased workers from a copper and lead smelter in
      northern Sweden. Control specimens have been collected from deceased normal
      individuals from four control areas. Lung, liver and kidney samples are collected
      with quartz instruments and stored in quartz ampoules to avoid contamination.
      Other samples, e.g. bone, brain, fat, hair, heart muscle, nails, skin and stomach
      are taken with common autopsy instruments and stored in acid-washed polyethene
      vessels. The samples are stored at -20 degrees C. The elements Sb, As, Cd, Cr,
      Co, La and Se are analyzed by neutron activation analysis, Pb and Zn by atomic
      absorption spectrophotometry. The findings over time can be related to a number
      of factors: normal values in tissues, airborne exposure and causes of death.
      Special attention is paid variation over time, reevaluation of threshold limit
      values and risk assessment.

PMID- 8272827
TI  - US-Canada Great Lakes Regional Specimen Bank Feasibility Study.
AB  - A study to examine the feasibility of establishing a Regional Specimen Bank in
      the Great Lakes area of the United States and Canada has recently been initiated
      by the Michigan Audubon Society. There are several existing formal and informal
      specimen banking facilities active in the region but their combined adequacy has
      not been evaluated. This feasibility study will establish the need and use of a
      regional bank and the institution(s) necessary to satisfy this need will be
      recommended. The study will address the scope required to meet present and future
      needs including the types of specimens to be represented in the bank, geographic
      coverage and protocols for collection, shipping, processing, analysis and
      storage. A management policy of the bank will be developed encompassing business
      operation, costs, governing structure and personnel requirements. The legal
      requirements of the bank will be determined with regards to the acquisition of
      samples, transport across national boundaries, access to specimens and
      information, and liability during operation. An effective information
      dissemination network will be recommended that is compatible with national and
      international partners, will facilitate technology and information transfer and
      support the quality and status of the bank. Determination of secure, long-term
      funding sources will be one of the key elements to ensuring a safe repository.
      This feasibility study is funded by the Great Lakes Protection Fund.

PMID- 8272828
TI  - A proposal for the establishment of the National Center for Phytogenetic Resource
      Conservation in the Venezuelan Republic.
AB  - The conservation of biodiversity, a valuable natural resource, is considered
      essential. In the face of continued threats to this resource the establishment of
      a National Center for Phytogenetic Resource Conservation in Venezuela is
      proposed. The proposed center would have the following main objectives: inventory
      of resources, establishment of a plant gene bank, basic ecological research,
      promotion of cultivation of useful but endangered species, promotion of national
      and international information-exchange, and protection of natural habitats. The
      organizational structure of the proposed center is outlined.

PMID- 8272829
TI  - Development of requirements for environmental specimen banking in ecological
      monitoring (exemplified by the Chernobyl NPP accident area).
AB  - Development of requirements for a data bank for natural media as a system of
      intercorrelated parameters to estimate system states are determined. The problems
      of functional agreement between experimental and calculation methods are analysed
      when organizing the ecological monitoring. The methods of forming the
      environmental specimen bank to estimate and forecast radioactive contamination
      and exposure dose are considered to be exemplified by the peculiarities of the
      spatial distribution of radioactive contamination in fields. Analysed is the
      temporal dynamics of contamination for atmospheric air, soil and water.

PMID- 8272830
TI  - The animal specimens of terrestrial and limnetic ecosystems in the environmental
      specimen banking programme of Germany.
AB  - In the terrestrial and limnetic sampling areas of the Environmental Specimen
      Banking Programme of Germany five animal species were collected. The goal of this
      paper is to show first the concept and criteria of the specimen selection for
      Environmental Specimen Banking with regard to the function of the specimens in
      the concept of ESB which refers to the role of the species in the trophic levels
      of the different ecosystems. Secondly, the substantial parts of the sampling
      operation procedures like the sampling design and the procedure of sampling are
      shown for five animal specimens.

PMID- 8272831
TI  - Banking of environmental samples for short-term biochemical and chemical
      monitoring of organic contamination in coastal marine environments: the GICBEM
      experience (1986-1990). Groupe Interface Chimie Biologie des Ecosystemes, Marins.
AB  - The GICBEM (Groupe Interface Chimie Biologie des Ecosystemes Marins) program
      consists of an evaluation of the ecosystem health status in the Mediterranean Sea
      mainly based on chemical and biochemical approaches. Specific chemical
      contaminants (polycyclic aromatic hydrocarbons (PAH), polychlorobiphenyls (PCB),
      heavy metals) in waters, sediments, and related biotransformation indicators in
      target organisms (mussels, fish) have been selected for a complete survey of the
      coastal waters. In order to provide an appropriate sampling program for
      standardization for each sampling cruise, various aspects have been studied: (a)
      parameters for the choice of the sample sites; (b) ways of collection the samples
      (waters, sediments, marine organisms); and (c) preparation of the samples for a
      short term storage on board ship and for further analyses in the ground
      laboratory. Methods of preparation and storage of the samples are described and
      could be used to initiate an environmental banking program including both
      possible retrospective analyses of chemical pollutants and biochemical
      indicators. Moreover, the correlation between chemicals (PAH) and biochemical
      (mixed function oxygenase activities) parameters has been studied and this
      demonstrates the capability of the enzyme activities as reliable pollution
      biomarkers.

PMID- 8272832
TI  - Investigation of roe deer--criteria for use as a bioindicator in specimen
      banking.
AB  - Some results are given for a 5-year study to establish standard operation
      procedures for roe deer (Capreolus capreolus). The criteria for bioindication of
      roe deer are listed for three forestry districts in the east of Lower Saxony
      (Braunschweig, Fallersleben, Lappwald). The organs investigated for use are
      liver, kidney, kidney fat, brain and were collected from animals with an intact
      abdomen and were packed in Teflon bags after being shot. The fresh samples are
      kept at +4 degrees C and prepared in a laboratory within 24 h. The organs were
      investigated for 20 organic and 15 inorganic constituents. Twenty-two detectable
      contaminants from different collections are evaluated by using a personal
      computer (PC) with a Statistical Package of Social Science (SPSS) program. The
      results show that liver is a good accumulating organ; organ size and the regular
      distribution of the contaminants throughout the organ are an advantage.
      Significant variations in concentrations of contaminants are observed in May
      until August; levels stabilize in September to November. Animals < 18 months of
      age should be selected from rather narrow and uniform biotopes for specimen
      banking during the periods of autumn to winter or May. Pooling of the samples is
      not recommended.

PMID- 8272833
TI  - Feathers of the magpie (Pica pica) as a bioindicator material for heavy metal
      pollution assessment.
AB  - This study examined the lead and cadmium content of external tail feathers of
      magpies from 15 localities in Poland, differing in degree of industralization and
      urbanization. Extremely high levels (up to 1500 micrograms/g dry wt. Pb and about
      40 micrograms/g dry wt. Cd) were found in samples from areas surrounding two zinc
      smelting works. The correlation between metal content in feathers and size of
      immission (mg/m2/y) at the sites of capture was 0.96 for Pb and 0.97 for Cd.
      Magpie tail feathers are recommended as a material for environmental
      biomonitoring.

PMID- 8272834
TI  - Bird feathers as bioindicators in areas of the German Environmental Specimen Bank
      -bioaccumulation of mercury in food chains and exogenous deposition of
      atmospheric pollution with lead and cadmium.
AB  - Feathers of selected bird species are used as pollution integrating biomonitors
      in areas of the German Environmental Specimen Bank. Lead, cadmium and mercury are
      analysed by Zeeman Solid Sampling AAS in feather vanes of selected bird species
      with different ecologies. In feather vanes there are quite different distribution
      patterns of lead and cadmium on the one hand and mercury on the other: lead and
      cadmium show strong gradients with respect to feather parts with high exposure to
      atmospheric influences. In contrast to this, mercury is distributed
      homogeneously. These different distribution patterns of lead and cadmium in
      feather vanes, in contrast to mercury, show that there are quite different
      incorporation paths. Cadmium and lead are deposited exogenously and indicate
      atmospheric pollution. Mercury in feathers is caused endogenously by food and
      physiology. Most of the mercury analysed in bird's feathers is in the ecotoxic
      methylated form and the contents in feathers depend on bioaccumulation in food
      chains. Feathers are suitable indicators for monitoring heavy metal pollution and
      give us information about incorporation paths and ecotoxic effects.

PMID- 8272835
TI  - The Julich Environmental Specimen Bank.
AB  - The environmental specimen bank of the Federal Republic of Germany represents the
      modern form of a systematically designed archive for the preservative storage of
      selected environmental specimens. Major aims of environmental specimen banks are:
      (i) retrospective identification and quantification of environmental chemicals
      including those not known at the time of storage; (ii) retrospective replicate
      analysis of samples stored under preservative conditions for the determination of
      inorganic elements or organic compounds already examined; and (iii) retrospective
      control of the success of legislative environmental protection measures in
      handling chemicals regarded as hazardous for man and the environment. Results of
      the environmental specimen bank at Julich by the Institute of Applied Physical
      Chemistry, Research Centre Julich, KFA, obtaining the initiated legislative
      regulations providing environmental pollution, are already proved for various
      compartments.

PMID- 8272836
TI  - Using a bank of predatory fish samples for bioindication of radioactive
      contamination of aquatic food chains in the area affected by the Chernobyl
      accident.
AB  - From the analysis of experimental data on radioactive contamination of various
      fish, it is suggested that predatory fish specimens can be used as bioindicators
      of radionuclide accumulation in reservoir food chains of the Chernobyl emergency
      area. The increased content of cesium radionuclides were detected in the muscle
      tissue of predatory fish collected in various regions of the Chernobyl emergency
      area. In most of the water bodies studied, maximum contamination levels of
      predatory fish by radionuclides of cesium occurred in 1987-1988, whereas in
      'nonpredatory' fish the concentration of cesium was maximum, as a rule, in the
      first year following the accident. The exposure doses of fish of various
      ecological groups and ages are estimated. The exposure doses of various
      population groups, using fish from contaminated water bodies, are also estimated.
      When forming the environmental data bank for the Chernobyl accident zone it is
      suggested that perch, pike-perch and pike be used as bioindicators of radioactive
      contamination of food chains.

PMID- 8272837
TI  - Monitoring heavy metals in the Gulf of Thailand using mussel watch approach.
AB  - Concentration of zinc, manganese, copper, chromium, nickel and cadmium were
      determined in the whole soft parts of the mussel, Perna viridis, collected along
      the coast of the Gulf of Thailand. Mussels were sampled from 10 locations, during
      1989-1990, following an earlier study in 1986. The trends of accumulations of
      investigated metals in the mussel were not higher than the previous study, except
      for the concentration of manganese and nickel. The levels of manganese and nickel
      in the mussel in 1989 and in 1990 were much higher than those reported previously
      for 1986. In addition, the level of cadmium, manganese and chromium in mussels
      from the western coast of the Gulf was higher than that from the other parts of
      the Gulf. However, the levels of such metals were within the acceptable limits
      with respect to the public health standards.

PMID- 8272838
TI  - Determination of PCBs and chlorinated hydrocarbons in marine mammal tissues.
AB  - Selected tissues (blubber, liver, kidney and muscle) from marine mammals, which
      were collected as part of the Alaska Marine Mammal Tissue Archival Project
      (AMMTAP), were analyzed for polychlorinated biphenyl (PCB) congeners and
      chlorinated pesticides. Concentrations of these compounds in the different
      tissues were compared and blubber was selected as the primary tissue for organic
      contaminant analyses for the AMMTAP based on higher levels (1-2 orders of
      magnitude) in this tissue compared to liver, kidney and muscle. Concentrations
      for 15 PCB congeners and 12 chlorinated pesticides are reported for 10 different
      animals of three species (northern fur seal, ringed seal and belukha whale) from
      five different sites.

PMID- 8272839
TI  - Contemporary and retrospective investigations of human milk in the trend studies
      of organochlorine contaminants in Sweden.
AB  - Milk from the Mothers' Milk Centre in Stockholm has been analysed for
      organochlorine contaminants in different time periods between 1967 and 1989. The
      contemporary investigations showed a decrease of the levels of certain pesticides
      and polychlorinated biphenyls (PCBs). The changes were related to the
      prohibitions and restrictions applied on the usage of the compounds. Milk
      samples, remaining from the contemporary studies, were archived from 1972 and
      onward. These samples were later reanalyzed and the investigations were extended
      to also include polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs)
      and specific congeners of PCBs, including non-ortho and mono-ortho coplanar PCBs.
      These retrospective investigations, of the same milk, showed a time related
      decrease in the concentrations also for these compounds. Calculating the levels
      by toxic equivalency factors relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (TCDD) it was found that PCBs contributed the major part of the toxic equivalents
      in milk.

PMID- 8272840
TI  - Ecological assessment of a region with PCB emissions using samples of soil,
      vegetation and breast milk: a case study.
AB  - An ecological assessment is performed by using a data bank of air, soil,
      vegetation and biology data from the area of a capacitor plant in Serpukhov,
      Russia. Over a number of years the use of PCBs for filling capacitors has brought
      about environmental contamination beyond the plant's sanitary zone, in particular
      along a stream where vegetables and berries are grown commercially. A correlation
      has been found between abnormally high concentrations of PCBs in breast milk of
      women living in the proximity of the plant and the occurrence of diathesis in
      babies. A number of remedial measures have been developed in conjunction with the
      city's sanitary service.

PMID- 8272841
TI  - Determination of inorganic constituents in marine mammal tissues.
AB  - Analyses of selected tissues from the Alaska Marine Mammal Tissue Archival
      Project (AMMTAP) have provided comprehensive information related to levels of 36
      trace elements and methyl-mercury in marine mammal tissues. Liver, kidney and
      muscle tissues from two northern fur seals, four ringed seals and six belukha
      whales were analyzed. The bulk of the investigated tissues and additional tissues
      from a total of 65 marine mammals are banked in the AMMTAP. The results are
      compared to literature values for trace element concentrations in marine mammal
      tissues and their relevance to environmental studies is discussed.

PMID- 8272842
TI  - Coordination of environmental specimen banking in the Nordic countries, its
      mission and strategy.
AB  - Under the authority of the Nordic Council of Ministers and their Working Group
      for Environmental Monitoring, a project for coordination of environmental
      specimen banking in the Nordic countries started in 1991. The project covers the
      established and planned central environmental specimen banks in Sweden, Norway,
      Denmark and Finland. The aim of the project is to coordinate and harmonize
      procedures and methods used in specimen banking such as, collection of material,
      transport, preparation and storage. In order to increase the possibilities for
      future international cooperation in monitoring and ecotoxicological scientific
      work, the Project Group will form the strategy for the continuing work in the
      Nordic countries. The Project Group will propose adaptation to commonly utilized
      methods for morphometric measurements of specimens and collection of some common
      species for future monitoring. The national responsibility for specimen banking
      in an international perspective will be emphasized.

PMID- 8272843
TI  - Herring gull eggs as bioindicators for chlorinated hydrocarbons (contribution to
      the German Federal Environmental Specimen Bank).
AB  - From its position in the marine food chain, the herring gull (Larus argentatus)
      is a suitable indicator for the level of contamination of its habitats with
      lipophilic chemicals, especially the chlorinated hydrocarbons. The gull's utility
      as an indicator is demonstrated by investigations performed at Trischen island in
      the Elbe estuary and Alte Mellum island situated in the Weser estuary, when
      judged by their ability to reflect variations in pollution levels. The use of the
      analysis technique developed and standardized for the German Environmental
      Specimen Bank gives comparable results for both temporal and spatial variations
      for contamination levels on the different islands in the Wadden Sea area (North
      Sea coast) of Germany.

PMID- 8272844
TI  - Concentration of elements in human brain: glioblastoma multiforme.
AB  - In this paper the results of two coordinated biomedical research projects are
      presented. The first project involves the determination of the average values of
      elements in normal human brain (20 individuals, age-group 65-75). 21 brain parts
      were selected from both hemispheres. Determinations were carried out by ICP-AES
      and INAA methods. The main (Na, K, Mg, Ca, Fe, P, S) and trace elements (Al, B,
      Ba, Co, Cr, Mn, Ni, Pb, Sr, Zn) were investigated. Quality control was ensured by
      using NBS Bovine Liver SRMs. On the basis of our investigations the regional
      distribution of elements can be given. The second goal was to detect the possible
      trace element changes in histopathologically selected brain regions from patients
      with glioblastoma multiforme. The majority of elements displayed no statistically
      significant differences between the studied groups, except the reduced levels of
      B and Zn and the increased level of Sr compared to the tissue from control
      individuals.

PMID- 8272845
TI  - Effective tools for the trace element characterization of tissues: neutron
      activation analysis and voltammetry.
AB  - The National Biomonitoring Specimen Bank at the National Institute of Standards
      and Technology applies a variety of techniques for extensive characterization of
      banked samples. To determine a large number of trace elements in small samples at
      low levels, instrumental neutron activation analysis has been combined with
      voltammetry. The two methods produce high quality data for thirty pollutant and
      biological trace elements. Results on archived specimens of human livers and
      intercomparisons of the two methods are reported.

PMID- 8272846
TI  - Prompt and delayed NAA techniques for the characterization of specimen bank
      materials.
AB  - The combined application of instrumental-, radiochemical- and prompt gamma
      neutron activation analysis to two spruce shoot materials from the German
      Environmental Specimen Bank (ESB) resulted in information on 50 elements,
      covering more than 50% of the total mass. Comparison of the element
      concentrations in the 'fingerprint' mode clearly indicated a different status of
      heavy metal pollution at the two distinct collecting sites.

PMID- 8272847
TI  - Radiochemical neutron activation analysis of Fe, Co, Zn, Sb and Se in biomedical
      and environmental samples.
AB  - A radiochemical neutron activation method has been developed for the simultaneous
      determination of Fe, Co, Zn, Sb and Se levels in cancerous breast tissue, milk
      samples and fugitive cement dust particulates. Various Standard Reference
      Materials from NIST, USA (Bovine Liver 1577a, Milk Powder 1549, Coal Fly Ash
      1633a and Urban Particulate Matter 1648), IAEA Vienna (Animal Muscle H-4, Milk
      powder A-11 and Soil-5) and NIES Japan (Pond Sediment) were also analysed for
      quality control. Samples together with standards were irradiated at a thermal
      neutron fluence of 10(13) ncm-2s-1 for 2 weeks. After dissolution/fusion together
      with carriers, the Fe was first separated by extracting with diethyl ether
      followed by extraction with cupferron in chloroform. From the aqueous phase Co
      and Zn were extracted using alpha-nitroso-beta-naphthol in chloroform and 2
      thenoyltrifluoroacetone in isobutylmethyl ketone, respectively. From another
      aliquot, Se was first complexed with o-phenylenediamine and extracted in benzene.
      Later Sb was extracted using KI and 4-(2-pyridylazo)-resorcinol (PAR) in benzene.
      The method yields reasonably accurate data for monitoring of trace elements in
      biomedical and environmental specimens.

PMID- 8272848
TI  - Levels of cesium-137 in seawater and fish from the Brazilian coast.
AB  - Considering environmental pollution problems and their impact on man, we have
      developed a research programme on environment monitoring. The aim of this work
      was to develop and to apply radiochemical methods for the analysis of cesium-137
      in marine samples, such as seawater and fish. Cesium-137 levels in surface
      seawater from the coastal region of Sao Paulo State range from 1.7 to 1.9 Bq.m-3.
      Samples of the five species of fish most consumed by local population were taken
      for the analysis of cesium-137. Levels for fish varied from 0.1 to 0.3 Bq.kg-1 of
      edible part. Data were used to calculate dose assessment.

PMID- 8272849
TI  - Reference materials and environmental specimen banking.
AB  - The preservation and protection of the environment has become a major challenge
      of our times since this has to be compatible with the ecological needs. The
      concept of Environmental Specimen Banking (ESB) acquires importance in providing
      the data base for deeper insight into ecochemical processes. Methodological
      development and preparation of reference materials (RMs) are also essential to
      such studies. Systematic efforts are to be made to acquire a good number of
      reference materials to be useful for analysis of toxic as well as essential
      components. Our experience has shown that it is possible to procure worthy and
      scientifically valuable specimens from soils and leafy food substances. Exploring
      preparation of suitable specimens from a country such as India might be a worthy
      exercise since it is possible to obtain clean specimens in this part of the
      world. Analytical data for determination of some trace and major elements in
      prepared RMs are presented.

PMID- 8272850
TI  - Use of DNA probes and plasmid capture in a search for new interesting
      environmental genes.
AB  - Adaptation to a stressed environment leads to organisms bearing DNA, encoding
      defense mechanisms. These mechanisms can be heavy metal resistance, catabolism of
      organic xenobiotics or stress reactions. Genes responsible for these mechanisms
      can be used for monitoring changing environments and therefore it can be
      important to store such bacteria in a bank. DNA-probing will be presented by the
      use of DNA fragments (of Alcaligenes eutrophus) coding for heavy metal resistance
      or xenobiotic degradation. Some strains do not grow on petri dishes and
      accordingly cannot be isolated from soils. In order to isolate plasmids from such
      strains, coding for heavy metal resistances or xenobiotic degradations, an
      exogenous plasmid isolation method was developed. In this method, the endogenous
      population is conjugated with Pseudomonas or Alcaligenes strains bearing a
      retrotransfer plasmid like RP4. In that way new plasmids from various sources
      including non-culturable strains could be obtained. With these methods, a large
      number of specimens adapted to stressed situations can be isolated or constructed
      (in the case of the exogenous plasmid isolation method). They form a source of
      interesting genetic material that can be used to restore polluted areas in
      natural areas, if necessary with the aid of genetic engineering (in vitro or in
      vivo techniques). Full knowledge of such bacteria and their resistance mechanisms
      or degradation pathways, can lead to new constructions able to attack
      recalcitrant mixtures of different organics and to resist heavy metals.

PMID- 8272851
TI  - Surfactants and complexing agents: new tasks for specimen banking?
AB  - Surfactants and complexing agents are chemical products that are released into
      the environment in large amounts after being used in cleaning processes, mineral
      flotation, pesticide formulations, etc. Although these compounds are largely
      degraded during sewage treatment in industrialized countries, significant amounts
      will be found in sediments or sewage sludges. Furthermore, large concentrations
      of these compounds can be found in small rivers and brooks in the vicinity of
      outfalls of sewage treatment plants. Since these compounds can be expected to
      alter the organic matrix of the soil (surfactants) or to remobilize heavy metals
      from soils or sediments (complexing agents), their occurrence in the environment
      and their effects have to be investigated to estimate their long-term risk
      potential. This could be a new task for specimen banking. To this end, (a)
      sensitive and specific detection methods for surfactants and complexing agents
      have to be developed at concentrations relevant to environmental occurrence, and
      (b) the effect of surfactants and complexing agents on the distribution of
      organic and inorganic pollutants in environmental compartments has to be
      investigated. Preliminary investigations show significant synergistic or
      antagonistic effects of various surfactants on the adsorption of pollutants at
      clay minerals.

PMID- 8272852
TI  - Activities related to environmental specimen banking in Japan.
AB  - Some experiments on the preservability of chemicals in environmental samples such
      as atmospheric particulate matters and mussel meat have been conducted by
      National Institute for Environmental Studies (NIES), Japan, as a preliminary
      study for future establishment of environmental specimen bank. NIES also has been
      operating a small experimental sample bank, storing several kinds of
      environmental samples. Closely cooperating with NIES, Environment Agency of Japan
      has been performing several types of nationwide environmental monitoring of
      chemical substances and some parts of the collected samples have been stored in
      the cold storage room for future use. A retrospective analysis of TBT and TPT in
      the fish using these stored samples showed an availability and usefulness of
      specimen bank for the long term monitoring of pollutants.

PMID- 8272853
TI  - Analytical and biological data of banked samples--a requirement to interpret
      accumulation and leaching of pollutants in biological specimens.
AB  - The accumulation of organic and inorganic pollutants in biological specimens
      depends, in many cases, not only on the atmospheric deposition or immission and
      contamination of the biotop, but also on the dynamic properties of the indicator.
      Thus the analytical data assume properties of process variables. In order to
      compare them in relation to space and time, it is often practical to refer them
      to defined conditions of the indicator (stationary phases, time cycles of low
      dynamics). If the accumulation varies consistently under identical conditions of
      contamination and if clear functional relations exist to the features of the
      indicator, for instance age, weight or ecological processes, it is necessary to
      normalize the analytical data, i.e. to refer them to a condition of the indicator
      which is defined meaningfully with regard to the ecology. Interactions with other
      inputs of substances may result in a differentiation of accumulation and leaching
      processes which is more or less specific for each element. Such knowledge is
      important for specifying the standard operation procedures and the evaluation as
      well as interpretation of analytic data, in particular, in the clarification of
      the ecotoxicological relations between the pollutant accumulation and the
      reaction of populations and ecosystems.

PMID- 8272854
TI  - Environmental specimen banking and poisons control--a new challenge.
AB  - Today clinical toxicology and poisons control are widely lacking objective
      criteria, e.g., analytical data, figures of kinetics and metabolism in acute and
      chronic poisoning. Co-operation between clinical toxicology and an environmental
      specimen bank for human tissue will help to overcome many difficulties and
      complement one another. The possible power of such a co-operation is demonstrated
      by the example of the institutions in Munster, Germany. The successful strategies
      used for setting-up an environmental specimen bank for human tissue may also be
      applied in clinical toxicology and experimental toxicology. The frame of a
      university medical clinic seems to be the ideal basis of an effective co
      operation of an Environmental Specimen Bank for Human Tissue, a Poisons Control
      Centre and clinical toxicology. In general a co-operation of an environmental
      specimen bank for human tissue and a poisons control centre will be cost-saving
      and beneficial to both and an environmental specimen bank for human tissue will
      gain the status of a unique tool for risk assessment of xenobiotics.

PMID- 8272855
TI  - Photon transmission tomography techniques for screening organs in biological
      specimen banking.
AB  - Biological specimen banking methodology dictates that when a number of specimens
      of a particular type are available then the selected specimen be representative
      of the population in question. It is apparent though that this sorting process
      may present a formidable task which can be facilitated by employing tomographic
      transmission techniques using photons. Thus it is possible to discriminate
      between and discern abnormalities in specimens by obtaining the distribution of
      the photon linear attenuation coefficient, a function of atomic number and
      physical density, in sections through the specimen whilst maintaining its
      integrity. Fresh and freeze-dried specimens of porcine kidney were initially
      examined under differing temperature conditions using a single point photon
      transmission method, which was not successful due to the heterogeneity of the
      tissues. Whereas photon transmission tomography is shown to be well suited in
      testing for homogeneity, highlights the importance of scanning before cryogenic
      treatment and provides the possibility of monitoring tissue status over storage
      period by observing small changes in linear attenuation coefficient.

PMID- 8272856
TI  - The JANUS serum bank.
AB  - The on-going JANUS project was initiated by the Norwegian Cancer Society in 1973.
      The serum bank comprises close to 0.5 million serum samples collected from
      170,000 donors. From 2-16 consecutive samples are available from each donor. The
      sera are stored at -25 degrees C. At regular intervals the JANUS-collection is
      matched against the files of the Norwegian Cancer Registry. From 1973 to 1991
      almost 5000 of the donors have developed some form of cancer. Frozen serum
      samples collected from a few months to 18 years prior to clinical recognition of
      their disease are consequently available for research purposes. The aim of the
      JANUS-project is to search in these premorbid sera for chemical, biochemical,
      immunological or other changes that might be indicative of cancer development at
      early stages. Gas chromatography-mass spectrometry and two-dimensional protein
      electrophoresis have been used to evaluate the stability of the frozen sera. Some
      recent findings are: CA125 is elevated several months prior to diagnosis of
      ovarian cancer; serum thyroglobulin may be a preclinical tumour marker in
      subgroups of thyroid cancer; low level of selenium in serum reflects increased
      risk of thyroid cancer; and raised antibodies in serum against Epstein-Barr virus
      is a risk factor for development of Hodgkin's disease. On-going research includes
      trace elements and cancer, and studies on lipid-profiles, diet and cancer. The
      serum bank may in principle be used for other purposes, e.g. in environmental
      studies. Analysis of sequential sera may determine chemical substances in the
      sera that might reflect differences in exposure to environmental pollutants in
      the period 1973-1991.

PMID- 8272857
TI  - The Danish Environmental Specimen Bank--status of establishment.
AB  - In 1988 the Ministry of Environment, Denmark appointed a committee with the
      purpose of investigating the need for and the requirements of a Danish
      Environmental Specimen Bank. The purpose of the Danish Specimen Bank will be to
      collect and store samples from the Danish environment in order to make
      retrospective studies. The sampling strategy is to select various biotopes and
      from each biotope to sample at least one species of plant, one species of
      invertebrate and one species of vertebrate. Six basic types including all
      fourteen subdivisions of biotopes were selected. Seven species of plants, four
      species of invertebrates and eleven species of vertebrates were selected. The
      number of biotic samples in all will be 119 every second year. No abiotic
      sampling strategy has yet been selected. Samples will be stored in containers
      cooled with liquid nitrogen, to preserve them for at least 50-100 years. The
      capital investment and the annual operating cost for the Danish Specimen Bank are
      estimated to 2,500,000 DKr. (350,000 $US) and 550,000 DKr. (70,000 $US),
      respectively.

PMID- 8272858
TI  - Biological specimen banking in Arctic research: an Alaska perspective.
AB  - The cryogenic archival of biological specimens for retrospective analysis is of
      significant value for present and future research on population genetics,
      pathology, systematics, toxicology and environmental monitoring. This realization
      is emphasized by the increasing support of this activity by various government
      agencies, institutions and international groups. The international Arctic
      community is no exception. Canada has been conducting such activities in
      association with environmental monitoring programs for many years. Similar
      efforts appear to be underway in other polar nations. From the perspective of the
      United States Arctic, the Alaska Marine Mammal Tissue Archival Project (AMMTAP)
      was the earliest organized effort to develop an environmental specimen bank
      specifically designed for longterm archival of biological specimens under
      cryogenic conditions. The AMMTAP emphasizes use of standardized rigorous sampling
      and archival protocols, procedures that minimize contamination of samples during
      collection and maintaining a detailed record of sample history. The development
      of this specimen bank, recent activities of this project and other cryogenic
      specimen banks being developed in Alaska are described.

PMID- 8272859
TI  - Development of the National Marine Mammal Tissue Bank.
AB  - The National Marine Mammal Tissue Bank (NMMTB) has been established as part of a
      comprehensive effort to obtain reliable information on contaminant levels in
      marine mammal tissues. A four component program consisting of the NMMTB,
      stranding networks, monitoring and quality assurance has been developed. The
      development and current status of the NMMTB and its relationship to the other
      three components will be described.

PMID- 8272860
TI  - Is dioxin a human carcinogen?

PMID- 8272861
TI  - The aftermath of the Gallo case.

PMID- 8272862
TI  - Regulation. German geneticists get some relief.

PMID- 8272863
TI  - A hearty endorsement for aspirin.

PMID- 8272864
TI  - Fighting HIV: a clue from hemophilia.

PMID- 8272865
TI  - Genes point to a new identity for Pacific pioneers.

PMID- 8272866
TI  - Fluorescent X-ray interference from a protein monolayer.
AB  - Fluorescent x-ray interference patterns have been observed from monolayers of
      both a metal-containing protein (ferritin) and a nonmetal-containing protein
      [bovine serum albumin (BSA)] bound on a gold substrate. These interference
      patterns have been used to determine structure data. The nonmetal-containing
      protein was first reacted with metal ions by means of a chelate compound to place
      the necessary chromophore in the molecule. The size of the ferritin core measured
      by a scanning electron microscope agrees with the value obtained from the x-ray
      interference experiments. In the BSA molecule, the measured interference fringe
      is consistent with the model in which the short axes of BSA molecules are
      perpendicular to the surface substrate.

PMID- 8272867
TI  - Target of the transcriptional activation function of phage lambda cI protein.
AB  - Activation of transcription initiation by the cI protein of phage lambda is
      thought to be mediated by a direct interaction between cl and RNA polymerase at
      the PRM promoter. Two negatively charged amino acid residues in the DNA binding
      domain of cI play a key role in activation, suggesting that these residues
      contact RNA polymerase. The subunit of RNA polymerase involved was identified by
      selecting polymerase mutants that restored the activation function of a mutant
      form of cI protein. Although previous studies suggest that several activators
      interact with the alpha subunit of RNA polymerase, the results here suggest that
      cI interacts with the sigma subunit. An arginine to histidine change near the
      carboxyl terminus of sigma specifically suppresses an aspartic acid to asparagine
      change in the activation region of cI. This finding supports the direct-contact
      model and suggests that a cluster of positively charged residues near the
      carboxyl terminus of sigma is the target of the negatively charged activation
      region of cI.

PMID- 8272868
TI  - Catalytic activity of an RNA domain derived from the U6-U4 RNA complex.
AB  - U6 RNA contains two regions that are essential for proper splicing of nuclear
      precursor messenger RNA (pre-mRNA). A comparison of putative secondary structures
      of the U6-U4 RNA complexes from different phyla revealed a conserved domain that
      is similar to the catalytic hammerhead RNA motif. Although no catalytic activity
      was detected in the mammalian U6-U4 RNA complexes, two nucleotide changes in U6
      RNA and one in U4 RNA conferred cleavage activity to the complex. Furthermore,
      the highly conserved domain of the wild-type complex, without the accompanying
      flanking regions, cleaved an RNA substrate and exhibited other characteristics of
      the hammerhead ribozyme. The possible involvement of this structure in pre-mRNA
      splicing is also discussed.

PMID- 8272869
TI  - Mitotic repression of RNA polymerase III transcription in vitro mediated by
      phosphorylation of a TFIIIB component.
AB  - Interphase cytosol extracts prepared from Xenopus laevis eggs are active in RNA
      polymerase III (Pol III) transcription. Addition of recombinant B1 cyclin to
      these extracts activates mitotic protein kinases that repress transcription.
      Affinity-purified p34cdc2-cyclin B kinase (mitosis-promoting factor) is
      sufficient to effect this repression in a simplified Pol III transcription
      system. This mitotic repression involves the direct phosphorylation of a
      component of the Pol III transcription initiation factor TFIIIB, which consists
      of the TATA box-binding protein (TBP) and associated Pol III-specific factors.
      The transcriptional activity of the TFIIIB-TBP fraction can be modulated in vitro
      by phosphorylation with mitotic kinases and by dephosphorylation with immobilized
      alkaline phosphatase.

PMID- 8272870
TI  - Location of cAMP-dependent protein kinase type I with the TCR-CD3 complex.
AB  - Selective activation of cyclic adenosine 3',5'-monophosphate (cAMP)-dependent
      protein kinase type I (cAKI), but not type II, is sufficient to mediate
      inhibition of T cell replication induced through the antigen-specific T cell
      receptor-CD3 (TCR-CD3) complex. Immunocytochemistry and immunoprecipitation
      studies of the molecular mechanism by which cAKI inhibits TCR-CD3-dependent T
      cell replication demonstrated that regulatory subunit I alpha, along with its
      associated kinase activity, translocated to and interacted with the TCR-CD3
      complex during T cell activation and capping. Regulatory subunit II alpha did
      not. When stimulated by cAMP, the cAKI localized to the TCR-CD3 complex may
      release kinase activity that, through phosphorylation, might uncouple the TCR-CD3
      complex from intracellular signaling systems.

PMID- 8272871
TI  - A transforming growth factor beta type I receptor that signals to activate gene
      expression.
AB  - Transforming growth factor beta (TGF-beta) is a multifunctional factor that
      regulates many aspects of cellular functions. TGF-beta signals through a
      heteromeric complex of the type I and type II TGF-beta receptors. However, the
      molecular mechanism of signal transduction by this receptor complex remains
      unresolved. The type II receptor belongs to a transmembrane receptor serine
      threonine kinase family. A new member of this receptor family (R4) was identified
      and shown to be a functional TGF-beta type I receptor on the basis of its ability
      to restore a TGF-beta-induced gene response in mutant cell lines lacking
      endogenous type I receptor. Both ligand binding and signaling of the R4 protein
      were dependent on the presence of a functional type II receptor. The type I
      receptor has an intrinsic serine-threonine kinase activity, which was essential
      for signal transduction.

PMID- 8272872
TI  - Association of transcription factor APRF and protein kinase Jak1 with the
      interleukin-6 signal transducer gp130.
AB  - Interleukin-6 (IL-6), leukemia inhibitory factor, oncostatin M, interleukin-11,
      and ciliary neurotrophic factor bind to receptor complexes that share the signal
      transducer gp130. Upon binding, the ligands rapidly activate DNA binding of acute
      phase response factor (APRF), a protein antigenically related to the p91 subunit
      of the interferon-stimulated gene factor-3 alpha (ISGF-3 alpha). These cytokines
      caused tyrosine phosphorylation of APRF and ISGF-3 alpha p91. Protein kinases of
      the Jak family were also rapidly tyrosine phosphorylated, and both APRF and Jak1
      associated with gp130. These data indicate that Jak family protein kinases may
      participate in IL-6 signaling and that APRF may be activated in a complex with
      gp130.

PMID- 8272873
TI  - Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor
      components.
AB  - A recently defined family of cytokines, consisting of ciliary neurotrophic factor
      (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), and interleukin-6
      (IL-6), utilize the Jak-Tyk family of cytoplasmic tyrosine kinases. The beta
      receptor components for this cytokine family, gp130 and LIF receptor beta,
      constitutively associate with Jak-Tyk kinases. Activation of these kinases occurs
      as a result of ligand-induced dimerization of the receptor beta components.
      Unlike other cytokine receptors studied to date, the receptors for the CNTF
      cytokine family utilize all known members of the Jak-Tyk family, but induce
      distinct patterns of Jak-Tyk phosphorylation in different cell lines.

PMID- 8272874
TI  - Targeting of G alpha i2 to the Golgi by alternative spliced carboxyl-terminal
      region.
AB  - Heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins) may
      participate in membrane traffic events. A complementary DNA (cDNA) was isolated
      from a mouse pituitary cDNA library that corresponded to an alternatively spliced
      form of the gene encoding the G protein alpha subunit G alpha i2. The cDNA was
      identical to that encoding G alpha i2 except that the region encoding for the
      carboxyl-terminal 24 amino acids was replaced by a longer region encoding 35
      amino acids that have no sequence similarity with G alpha i2 or other members of
      the G protein family. This alternative spliced product and the corresponding
      protein (sGi2) were present in several tissues. Specific antibodies revealed that
      sGi2 was localized in the Golgi apparatus, suggesting a role in membrane
      transport. Thus, alternative splicing may generate from a single gene two G
      protein alpha subunits with differential cellular localization and function.

PMID- 8272875
TI  - "Primum, non nocere".

PMID- 8272876
TI  - Malignancies may be treated by surgical, radiation, or medical oncologists.

PMID- 8272877
TI  - Case of the season. Silo filler's disease in a patient with prior Swyer-James
      syndrome.

PMID- 8272878
TI  - Basic mechanisms and general morphology of radiation injury.

PMID- 8272879
TI  - Radiation changes in the lung.

PMID- 8272880
TI  - Radiation-induced heart disease: imaging features.

PMID- 8272881
TI  - Imaging findings in postradiation changes of the thyroid and parathyroid glands.

PMID- 8272882
TI  - Radiation changes in the breast.

PMID- 8272883
TI  - Magnetic resonance findings in skeletal muscle tears.
AB  - Magnetic resonance (MR) images of skeletal muscle tears can clearly delineate the
      severity of muscle injury. Although MR imaging is seldom necessary in patients
      with acute muscle trauma, it can be helpful in deciding on clinical management.
      The two major MR findings in acute muscle tears are deformity of the muscle and
      the presence of abnormal signal reflecting hemorrhage and edema. In acute tears,
      methemoglobin within the extravascular blood causes high-signal areas on both T1-
      and T2-weighted images. With partial tears, the blood may dissect in a
      distinctive linear pattern along the muscle bundles and fibers. As healing
      begins, the muscle signal diminishes, first on the T1-weighted images and then on
      the T2-weighted images. When there is residual abnormal signal on images obtained
      more than several months after the injury, it is presumed to represent hemorrhage
      from recurrent tears. In patients with a questionable history of a remote injury,
      the clinical presentation may be that of persistent pain or a soft tissue mass.
      In these cases MR imaging may identify the cause of the pain and can exclude a
      neoplasm by proving that the mass is a hypertrophied or retracted muscle. Thus,
      MR imaging has a limited, but occasionally important role in selected patients
      with skeletal muscle tears.

PMID- 8272885
TI  - MRI of soft tissue abnormalities: a primary cause of sickle cell crisis.
AB  - The early manifestations of sickle cell crisis in soft tissues are important to
      recognize, though rarely manifest on radiographs and difficult to evaluate on
      computed tomography and bone scans. Documentation is critical, however, if
      appropriate judgments as to emergency treatment versus conservative measures are
      to be made. Seventeen adults seen in the emergency room or hospitalized in
      presumed sickle cells crisis underwent magnetic resonance imaging within 24-72 h
      of presentation. Results indicate that magnetic resonance imaging is a sensitive
      modality for documenting early soft tissue pathology which may be the predominant
      or sole cause of sickle cell crisis.

PMID- 8272886
TI  - SLAP lesions of the glenoid labrum diagnosed with MR imaging.
AB  - Tears of the superior portion of the glenoid labrum in patients without shoulder
      instability have recently been described. These tears, which include the "anchor"
      of the biceps tendon to the labrum, have been labeled "SLAP lesions" (superior
      labrum anterior to posterior). This study was performed to determine the magnetic
      resonance (MR) findings in patients with SLAP lesions. Retrospective review of
      the shoulder arthroscopy reports on patients who underwent MR imaging using a 1.5
      T unit and subsequent arthroscopy by a single surgeon identified six patients
      with SLAP lesions (average age 36 years, range 17-65 years). MR images
      demonstrated atypical morphology indicative of tear in the superior portion of
      the labrum in four of the six patients, but only one tear had been identified
      preoperatively. Radiologists interpreting MR images of the shoulder should be
      aware of the MR findings of SLAP lesions as these tears can be a significant
      cause of patient disability and are difficult to diagnose clinically.

PMID- 8272884
TI  - Benign bone-forming lesions: osteoma, osteoid osteoma, and osteoblastoma.
      Clinical, imaging, pathologic, and differential considerations.
AB  - The benign bone lesions--osteoma, osteoid osteoma, and osteoblastoma--are
      characterized as bone-forming because tumor cells produce osteoid or mature bone.
      Osteoma is a slow-growing lesion most commonly seen in the paranasal sinuses and
      in the calvaria. When it occurs in the long bones, it is invariably juxtacortical
      and may need to be differentiated from, among others, parosteal osteosarcoma,
      sessile osteochondroma, and a matured juxtacortical focus of myositis ossificans.
      Osteoid osteoma and osteoblastoma appear histologically very similar. Their
      clinical presentations and distribution in the skeleton, however, are distinct:
      osteoid osteoma is usually accompanied by nocturnal pain promptly relieved by
      salicylates; osteoblastoma arises predominantly in the axial skeleton, spinal
      lesions constituting one-third of reported cases. This review focuses on the
      application of the various imaging modalities in the diagnosis, differential
      diagnosis, and evaluation of these lesions. Their histopathology also is
      discussed, and their treatment briefly outlined.

PMID- 8272887
TI  - Hydatid disease of the soft tissues of the lower limb: findings in three cases.
AB  - Three cases of hydatid disease are reported, all presenting as soft tissue
      lesions in the lower extremities. All three cases were studied with ultrasound
      (US), two with computed tomography (CT), and two with magnetic resonance (MR)
      imaging techniques. Two patients presented with multivesicular lesions which were
      considered diagnostic of hydatid disease. The third patient showed a lesion with
      a predominantly solid pattern, closely mimicking a soft-tissue neoplasm. US was
      not diagnostic, but MR outlined vesicular structures and a fibrous pericyst.
      Hydatid disease presenting in the soft tissues can therefore be diagnosed with
      confidence when it shows multivesicular lesions but MR may be the most useful
      imaging technique when a complex or solid pattern is present.

PMID- 8272888
TI  - Fatigue fractures of the sacrum in children: two case reports and a review of the
      literature.
AB  - We present the clinical and radiological features of two children with fatigue
      fractures of the sacrum. Both patients were active, had no underlying bone
      disease and presented with insidious onset of low back pain. Plain radiography
      was non-contributory to the diagnosis. In both patients a focal area of increased
      activity was present in the lateral aspect of the sacrum on bone scintigraphy,
      which corresponded to linear medullary sclerosis in the sacral ala demonstrated
      by computed tomography. Magnetic resonance imaging in one patient revealed a
      linear signal void in the sacral ala on T1- and T2-weighted images. This was
      surrounded by diffuse low marrow signal on T1-weighted images, and increased
      marrow signal on T2-weighted images. Fatigue fractures of the sacrum should be
      considered in the differential diagnosis of low back pain in children. An
      awareness of their appearance on magnetic resonance imaging is important as this
      modality is increasingly utilised, particularly in children.

PMID- 8272889
TI  - Klippel-Feil syndrome: patterns of bony fusion and wasp-waist sign.
AB  - Cervical spine radiographs of 33 patients with Klippel-Feil syndrome were studied
      for patterns of bony fusion and presence of wasp-waist sign. Five patients were
      found to have the classic features of massive cervical fusion. Two patients with
      two adjacent levels of bony fusion showed a wasp-waist sign. Fusion at one level
      of the cervical spine accounted for 26 remaining cases. The wasp-waist sign was
      observed in 14 of the cases in which there was complete vertebral interbody
      fusion, making this finding a valuable radiologic sign. Partial anterior or
      posterior vertebral interbody fusion, or isolated fusion of the neural arch,
      however, may or may not be associated with the wasp-waist sign. Klippel-Feil
      syndrome, easy to recognize when presenting with classic features or when
      associated with the wasp-waist sign, may be confused with a variety of other
      entities.

PMID- 8272890
TI  - Os odontoideum in identical twins: perspectives on etiology.
AB  - Most authorities favor the hypothesis of an acquired etiology of os odontoideum.
      We present the cases of identical twin sisters with os odontoideum in association
      with a congenital partial fusion of the posterior elements of the second and
      third cervical vertebrae, and discuss the implications. We believe that this is
      the first report of familial os odontoideum in a context which suggests a genetic
      etiology.

PMID- 8272891
TI  - Case report 789: Dorsal defect of the left patella.
AB  - Dorsal defect of the patella is an uncommon but well known abnormality. It is
      believed to be an incidental finding that should not merit further intervention.
      However, the association of patellofemoral symptoms and a dorsal defect of the
      patella suggests abnormality of the cartilage overlying the defect. Resection of
      this area of abnormal cartilage has resulted in relief of symptoms in some
      patients. A patient who had a dorsal defect of the patella and persistent
      symptoms had MR imaging. The MR scans showed signal inhomogeneity with streaks of
      high signal in the cartilage overlying the lesion on both T1-weighted and T2
      weighted images. Drilling of the defect relieved his pain.

PMID- 8272892
TI  - Case report 807: Infantile desmoid-type fibromatosis.
AB  - A case of infantile desmoid-type fibromatosis has been described and discussed.
      The clinical and pathological features were described, and the interrelationship
      of this entity with others, together with the wide range of benign structures,
      was discussed. Other cases resembling this one have been described.

PMID- 8272893
TI  - Case report 808: Avulsion fracture of the greater trochanter.
AB  - The differential diagnosis of unexplained hip pain after trauma in patients with
      normal radiographs includes both soft tissue and bony abnormalities. We have
      presented a case of an isolated fracture of the greater trochanter in an adult
      with normal radiographs where the diagnosis was made by MRI.

PMID- 8272895
TI  - Case report 810: Giant cell tumor of the first metatarsal.
AB  - And unusual case of giant cell tumor in a 3-year-old girl has been presented. The
      topic of giant cell tumors has been discussed at length. The pathology and the
      differential diagnosis have been considered. The incidence of giant cell tumors
      in children and adolescents has also been reviewed and proved to be extremely
      rare.

PMID- 8272894
TI  - Case report 809: Squamous cell carcinoma of the skin invading the shoulder.
AB  - Bone invasion by squamous cell carcinoma (SCC) is very rare in locations other
      than the head and neck region. The case of a 30-year-old man with slow-growing
      SCC of the shoulder region, aggressively invading neighboring bony structures,
      was presented.

PMID- 8272896
TI  - Case report 811: Avulsion injury of radical tuberosity (avulsion of the distal
      attachment of the biceps brachii).

PMID- 8272897
TI  - Case report 812: Well-differentiated osteosarcoma arising in the right third rib.
AB  - A rare case of intraosseous well-differentiated osteosarcoma in a 9-year-old boy
      arising in the rib is reported. A bone scintiscan was found to be useful in
      accurately diagnosing this lesion as malignant tumor, because plain films and CT
      scan seemed to indicate a benign tumorous condition.

PMID- 8272898
TI  - Medically unnecessary cesarean section births: introduction to a symposium.
AB  - Between 1965 and 1986, the United States cesarean section rate increased from 4.5
      to 24.1%. Increasingly, childbearing women and their advocates, along with many
      others, have recognized that a large proportion of cesareans confers a broad
      array of risks without providing any medical benefit. A growing literature
      examines the diverse causes of medically unnecessary cesareans and the diverse
      effects of surgical birth on women, infants, and families. Various programs and
      policies have been proposed or implemented to reduce cesarean rates. In recent
      decades, many other nations have also experienced a sharply escalating cesarean
      section rate. It is reasonable to conclude that a largely uncontrolled
      international pandemic of medically unnecessary cesarean births is occurring. The
      level of political, analytic, and programmatic activity that has occurred in the
      U.S. regarding medically unnecessary surgical births does not seem to be
      paralleled in other nations with sharply escalating rates. This symposium was
      organized with the objective of presenting the U.S. experience with various
      dimensions of the problem of medically unnecessary cesareans to an international
      audience. Although preliminary and inadequate, it is hoped that this experience
      will encourage policy leaders and investigators throughout the world to recognize
      and address the problem of run-away cesarean section births. The first section of
      this introduction summarizes the U.S. experience with medically unnecessary
      cesareans from the perspective of trends, causes, consequences, and solutions.
      The second section covers the same topics, presenting selected material from
      various other nations throughout the world. In the course of these overviews, I
      introduce the symposium's seven contributions, most of which focus on
      circumstances in the U.S.

PMID- 8272899
TI  - Caesarean section in Britain and the United States 12% or 24%: is either the
      right rate?
AB  - The rate of caesarean section (CSR) in Great Britain (GB) and the U.S.A., 12% in
      England in 1989 ascertained from a survey performed by the authors, and 24%
      according to official U.S. figures, is higher than warranted by the known and
      agreed obstetric indications for this operation, which suggest a rate of 6-8%
      would be adequate. It is argued that the fall in perinatal mortality which has
      occurred over the period during which the CS rate has risen is not the main
      reason for this fall. The training of obstetricians to deal with anxiety,
      provision of primary maternity care by appropriately trained midwives and general
      or family practitioners, and changes in management protocols could cut the CSR.
      The number of women undergoing surgery every year in the U.K. could be reduced by
      20,000 and in the U.S.A. by 470,000 if the rate of 6% were achieved. In studies
      of midwifery care the CSR is even lower and it is possible that labour proceeds
      more efficiently if the woman knows her caregivers and labours at home, as in The
      Netherlands. Although CS is much safer than in the past it is still more likely
      to result in the death of the woman and has significant morbidity for the woman
      and economic costs for society.

PMID- 8272900
TI  - The Mount Sinai cesarean section reduction program: an update after 6 years.
AB  - A six year follow-up evaluation of our original cesarean section reduction
      program is presented. While establishing obstetric practice guidelines was
      accomplished, two prerequisites remain critical: lowering cesarean utilization
      was to be accomplished without harm to mother or fetus, and a target rate was
      prospectively determined. The results after 6 years indicate that total cesarean
      rates of 10-12% can consistently be achieved without adverse outcome.
      Additionally, operative vaginal procedures were employed less that 3% of cases.
      Separate analysis of 580 breech deliveries failed to show an effect of route of
      delivery on mortality. This effort indicates that long-term reductions and
      cesarean utilization are possible with a comprehensive departmental program
      designed to accomplish achieving a target rate of 11%.

PMID- 8272901
TI  - Cesarean section: medical benefits and costs.
AB  - Cesarean section rates have risen dramatically in the U.S. over the past 20
      years. Although infant mortality has declined during the same period, there is
      little evidence that more frequent cesarean surgery is the cause. Cesareans save
      lives or benefit health in certain circumstances, but the incidence of those
      indications has not increased. Cesarean section also has risks, the most
      significant for the infant being iatrogenic prematurity or respiratory disease.
      Maternal mortality is 2-4 times higher and morbidity is 5-10 times higher after a
      cesarean compared to vaginal birth. The four indications responsible for most of
      the rise in cesarean rates--previous cesarean, dystocia, breech presentation, and
      fetal distress--are those conferring the least clear-cut benefit.
      Demographically, women who are most likely to experience pregnancy complications,
      low birth weight births, or infant mortality are least likely to have a cesarean.
      Social, economic, and other factors seem to have a greater influence on the
      decision to perform a cesarean than does expected medical benefit. The
      development of neonatal intensive care, expanded access to prenatal care, and
      greater availability of abortion and family planning have contributed more to
      falling infant mortality. It has been estimated that approximately half the
      cesareans currently performed in the U.S. are medically unnecessary, resulting in
      considerable avoidable maternal mortality and morbidity, and a cost of over $1
      billion each year.

PMID- 8272902
TI  - Midwifery care and out-of-hospital birth settings: how do they reduce unnecessary
      cesarean section births?
AB  - In studies using matched or adjusted cohorts, U.S. women beginning labor with
      midwives and/or in out-of-hospital settings have attained cesarean section rates
      that are considerably lower than similar women using prevailing forms of care-
      physicians in hospitals. This cesarean reduction involved no compromise in
      mortality and morbidity outcome measures. Moreover, groups of women at elevated
      risk for adverse perinatal outcomes have attained excellent outcomes and cesarean
      rates well below the general population rate with these care arrangements. How do
      midwives and out-of-hospital birth settings so effectively help women to avoid
      unnecessary cesareans? This paper explores this question by presenting data from
      interviews with midwives who work in home settings. The midwives' understanding
      of and approaches to major medical indications for cesarean birth contrast
      strikingly with prevailing medical knowledge and practice. From the midwives'
      perspective, many women receive cesareans due to pseudo-problems, to problems
      that might easily be prevented, or to problems that might be addressed through
      less drastic measures. Policy reports addressing the problem of unnecessary
      cesarean births in the U.S. have failed to highlight the substantial reduction in
      such births that may be expected to accompany greatly expanded use of midwives
      and out-of-hospital birth settings. The present study--together with cohort
      studies documenting such a reduction, studies showing other benefits of such
      forms of care, and the increasing reluctance of physicians to provide obstetrical
      services--suggests that childbearing families would realize many benefits from
      greatly expanded use of midwives and out-of-hospital birth settings.

PMID- 8272903
TI  - The effect of physician characteristics on clinical behavior: cesarean section in
      New York State.
AB  - This study examines 65,784 obstetric deliveries occurring in 1986 in New York
      State, attended by 1740 different physicians. Cesarean section rates, and rates
      of reporting of dystocia and fetal distress, are calculated by physicians' year
      of graduation from medical school, U.S. or foreign medical graduate (FMG),
      physician sex, board certification, and professorial appointment. Probit
      regressions are estimated, in which the dependent variable is whether an
      individual delivery is vaginal or cesarean section. Crude cesarean section rates,
      cross-tabulations, and probit regressions all show physician characteristics to
      influence cesarean section rates significantly. FMGs are significantly more
      likely to deliver by cesarean section, both overall and when all other relevant
      factors are controlled for. Cesarean section rates by FMGs vary somewhat
      according to U.S. vs non-U.S. birthplace, and country or area where educated.
      Unlike others, the authors fail to find more recently graduated physicians to
      have higher cesarean section rates. Indeed, their rates for dystocia are
      significantly lower, when other factors are controlled for. Women physicians have
      a slightly lower cesarean section rate overall when other factors are controlled
      for, but a higher rate for dystocia. Board certified obstetricians have
      significantly higher, and physicians with professorial appointments lower
      cesarean section rates, though the direction of causation is not always clear.
      The authors conclude that the effect of physician characteristics on clinical
      behavior is a fruitful line of inquiry, and that in particular the results
      pertaining to FMGs warrant further investigation.

PMID- 8272904
TI  - Explaining excessive rates of cesareans and other childbirth interventions:
      contributions from contemporary theories of gender and psychosocial development.
AB  - The current rate of cesarean sections in the U.S. is too high. Numerous mothers
      and babies are being placed at unnecessary risk of medical, behavioral and
      psychological complications. The problem has proven resistant to solution on a
      large scale, despite serious efforts on the part of a variety of individuals and
      groups. This paper considers reports on the interactions between obstetricians
      and mothers in labor in light of findings and theory in the areas of gender and
      psychosocial development. Examination of processes and standards of care in light
      of these findings and theory leads to the conclusion that the present model of
      obstetric services is consistent with a masculine style, and offers far less than
      optimal care for women. In fact, the gender-inappropriate elements of the model
      itself probably contribute to the excessive rates of interventions in labor.
      Social, political and historical factors are seen to support the obstetric model
      as is, leading to some pessimism about the possibility that the model could be
      modified sufficiently without major social change. The obstetric model is
      compared briefly with the more gender appropriate model of care provided by
      midwives.

PMID- 8272905
TI  - Psychosocial impact of cesarean section on the family: a literature review.
AB  - This paper reviews the literature linking cesarean section with maternal,
      paternal and infant/child/familial psychosocial impact. Cesarean section is
      discussed as both major surgery, with concomitant physical and psychosocial
      ramifications, and as an increasingly and routinely utilized method of birthing.
      Also considered are factors associated with the current high cesarean birthrate,
      as well as socio-cultural based factors contributing to varying parental
      conceptualizations and expectations of birthing. Empirical research published
      during the past 14 years associates cesarean section with adverse maternal and
      paternal psychosocial outcome and with possible negative consequences for the
      infant/child. Weaknesses/flaws of psychosocial impact studies are discussed,
      including timing and location of data collection, sample bias, and the
      difficulties of analyzing vast arrays of complex variables. Enumeration of both
      physical/environmental variables and psychosocial/cultural variables of maternal
      psychosocial impact are included. A number of these variables form a profile of a
      woman at relatively high risk of adverse psychosocial outcome. This profile is
      useful in identification of approaches and strategies for the prevention of
      adverse psychosocial outcome as well as in the identification of women who might
      benefit from focused perinatal psychotherapeutic services. The importance of
      psychotherapeutic services for cesarean families, including local, national and
      international cesarean support networks, is discussed. Emphasis is given to the
      importance of increased awareness of psychosocial issues and of current research
      on the part of medical care providers and health policy experts.

PMID- 8272906
TI  - Think melanoma.
AB  - Every physician's office should be a melanoma detection station. Identification
      and surgical excision of early melanoma is today's best answer to reducing the
      death rate from this treacherous disease. Public awareness of melanoma is gaining
      momentum. Melanoma education for physicians is vital if the battle against
      melanoma is to be successful. This presentation is a challenge to all physicians
      and students of medicine to identify patients at risk for melanoma and to follow
      up with a skin scan to search for suspicious spots on all patients with risk
      factors for melanoma as a part of their physical examination. We need to teach
      individuals at risk to do self-examination, to report immediately any recent
      growth changes in an existing mole or any recently acquired pigmented lesion, and
      to practice the rules of safe sun exposure. Because securing a suitable specimen
      of tissue for biopsy and proper interpretation of sections are paramount in
      patient management and understanding prognosis, we present guidelines for
      performing a proper biopsy.

PMID- 8272907
TI  - Drug abuse in an obstetric population of a midsized city.
AB  - Drug abuse during pregnancy has attracted national attention, but most studies
      are from large cities. This study is concerned with the indigent pregnant
      patients in a midsized city in the southeastern United States. In a 23-month
      study, 2,442 patients were delivered of neonates. Using specific criteria, 511
      patients were tested for drug abuse. A positive test was identified in 156 (31%),
      cocaine being the most common agent. During 2 months of random testing, 15
      patients (16%) had positive drug screens. Comparison of drug-positive pregnant
      patients with general obstetric patients identified many adverse obstetric and
      perinatal outcome data. Drug-positive patients weighed less, were older, were
      prone to not seek prenatal care, and were more likely to deliver prematurely and
      have a growth-retarded infant. Drug abuse in this population had significant
      impact on the health of the patient and her unborn infant.

PMID- 8272908
TI  - Transportation of children with special seating needs.
AB  - As of 1986, all 50 states had implemented mandatory child restraint laws. When
      used correctly, restraint systems have been proven to reduce the number of
      fatalities, hospitalizations, and injuries. To date, there is little information
      regarding compliance with restraint systems for disabled children. There are no
      data available on fatalities of or injuries to disabled children. This study
      assessed the restraint system (if any) used in the transportation of disabled
      children with special restraint needs. We conducted a survey to determine the
      restraint practices used in transporting these children to school, to our
      outpatient clinic, and around home. Our survey found that two thirds of the
      handicapped children reviewed were transported unsafely in at least one mode of
      transportation. We recommend that health care providers review the transportation
      needs of their handicapped patients in order to ensure safe transportation.

PMID- 8272909
TI  - Needs assessment for reducing infant mortality in Baltimore City: the Healthy
      Start Program.
AB  - Needs assessments are essential for policy formulation and the appropriate design
      of intervention programs. Recent nationwide data show that among large
      metropolitan areas of the United States, Baltimore has one of the highest infant
      mortality rates and ranks in the worst top 10 for blacks and the top 5 for whites
      for most indicators of poor pregnancy outcome. In this paper, we present the
      methods and results of a needs assessment that used multiple sources of routinely
      collected data and was conducted for the purpose of identifying intervention
      factors contributing to infant mortality in Baltimore City. This needs assessment
      was used by the Baltimore City Health Department to successfully secure funding
      for the federal Healthy Start Infant Mortality Prevention Initiative. We present
      the results of the analyses, along with some of the proposed interventions that
      resulted from the needs assessment. We also discuss the limitations of this type
      of needs assessment as well as suggestions for future needs assessments for the
      design of interventions to improve perinatal health.

PMID- 8272910
TI  - Outbreak of gastroenteritis due to Salmonella enteritidis from locally produced
      grade A eggs, South Carolina.
AB  - Recent investigations of outbreaks of Salmonella enteritidis gastroenteritis
      among humans, especially in the northeastern United States, implicate grade A
      shell chicken eggs as the likely vehicle of transmission. In April 1991 we
      investigated an outbreak of S enteritidis infections after a wedding anniversary
      celebration in Beaufort, South Carolina. Sixty-eight percent of persons who ate a
      macaroni and cheese dish, but none of the 16 attendees who did not, became ill (P
      < .001). The chef used six grade A eggs in the macaroni and cheese and may have
      undercooked it. The egg supplier processed eggs exclusively from farms in South
      Carolina and North Carolina. This outbreak suggests that the epidemic of S
      enteritidis in flocks of laying hens the consequent threat of human infection has
      spread to the Carolinas.

PMID- 8272911
TI  - Chronic gastritis associated with infection due to Helicobacter pylori in
      southern Appalachian veterans with dyspepsia.
AB  - A prospective study of infection due to Helicobacter pylori in 104 Southern
      Appalachian veterans with upper gastrointestinal symptoms revealed a prevalence
      of 67%. There was no age difference observed between those with and without H
      pylori. The organism was shown to be present in 12 of 13 patients with duodenal
      ulcer (92%), 6 of 10 with gastric ulcer (60%), and 52 of 81 with nonulcer
      dyspepsia (64%). Using culture as standard, the urease test showed a sensitivity
      of 76% and specificity of 100%, while the biopsy stain had a sensitivity of 97%.
      The presence of acute inflammation in the antrum and body of the stomach closely
      correlated with the presence of the organism. Somewhat at variance with previous
      studies, our study indicated that H pylori in the body mucosa was strongly
      associated with chronic superficial gastritis with and without acute
      inflammation. Such a finding may reflect the natural history of infection due to
      H pylori and the advanced age of our patients.

PMID- 8272912
TI  - Necrotizing surgical infection and necrotizing fasciitis in obstetric and
      gynecologic patients.
AB  - Necrotizing fasciitis (NF) is a rapidly progressive disease characterized by
      extensive necrosis of the skin, fascia, and subcutaneous tissue, with sparing of
      the underlying muscle. Diabetes mellitus, Bartholin's gland abscess, and recent
      surgical procedures (including episiotomy) are factors often found in obstetric
      and gynecologic patients. Mortality in this group of patients is higher than in
      the general surgical population. Death is usually due to overwhelming sepsis,
      renal and respiratory failure, and multiple organ failure. The infections are
      usually polymicrobial, with alpha-hemolytic streptococci, gram-negative
      coliforms, and anaerobic bacteria. Lower survival has been reported in large
      series when the groin is involved or when the general nutritional state is poor.
      From October 1988 to August 1990, we treated five patients with necrotizing
      fasciitis. Certain important characteristics of such patients have not been
      discussed in the obstetric and gynecologic literature. Nutritional status, with
      special emphasis on total protein, albumin, and the effects of alcoholism, has a
      significant impact on mortality. Nutritional support of these patients may
      improve survival. To limit the impact of secondary infections, surgical
      approaches should be modified by the anatomic location of the initial lesions.
      More frequent debriding in the operating room and early fecal diversion are
      recommended.

PMID- 8272913
TI  - Neonatal fungemia and amphotericin B.
AB  - Disseminated candidemia is a common nosocomial infection in the neonatal
      intensive care unit, though only a few studies have reported the outcome of
      amphotericin B therapy in neonatal candidiasis. Our treatment regimen consisted
      of an initial daily amphotericin B dose of 0.5 mg/kg. (For infants weighing > 1
      kg, the second dose was increased to 1 mg/kg.) At 3 to 5 days, if the blood
      culture was negative, amphotericin B therapy was changed to every other day and
      continued for a total of 10 doses. Records of 36 patients given this regimen were
      reviewed for signs of toxicity or treatment failure. The mean birth weight was
      988 +/- 510 g, and the gestational age was 28 +/- 3.9 weeks. The patients were
      ventilated for 13 +/- 15 days and had central lines for 6.7 +/- 9.3 days before
      development of candidemia. The mean age at onset of candidemia was 29.1 +/- 19.8
      days. The interval from culture to treatment was 2.9 days. Six of 36 patients
      died, 2 of candidal meningitis and 4 of complications unrelated to candidal
      infection. Thirteen (36%) of the patients had candidal pustules during the course
      of their disease; 1 had osteomyelitis. There was no evidence of toxicity from
      this drug regimen and no apparent treatment failures. There were no changes in
      BUN and creatinine before or during therapy and no change in total urinary
      output. Blood cultures became sterile except in one patient who died on the first
      day of therapy. Most of the patients in this study had candidemia in the absence
      of a central indwelling catheter. Further prospective pharmacokinetic and
      therapeutic studies are warranted for this regimen of amphotericin B, which
      carries a low risk for toxicity.

PMID- 8272914
TI  - Frequency and correlates of bacteriuria among children with neurogenic bladder.
AB  - Bacteriuria is a common clinical problem among children with neurogenic bladder
      due to meningomyelocele or traumatic spinal cord injury. To determine the
      frequency of bacteriuria among affected children at our institution, we obtained
      257 urine specimens from 105 children being seen as outpatients for routine care
      over a 2-year study period. Specimens were obtained via catheterization. Almost
      half of these specimens (110/257 or 43%) yielded positive results when tested for
      urinary pathogens. To assess whether any characteristics of these children were
      related to the likelihood of bacteriuria, we analyzed further a subgroup of 46
      children with normal renal ultrasonography from whom two to five specimens were
      obtained. There were no statistically significant associations between the
      likelihood of bacteriuria and the following characteristics: age, gender,
      socioeconomic status, level of spinal cord lesion, voiding technique, and use of
      prophylactic antibiotics. Children with neurogenic bladder are at high risk for
      bacteriuria. The pathogenesis of this bacteriuria, its part in deterioration of
      the urinary tract, and the possible means of its prevention in this special
      population all deserve further study.

PMID- 8272915
TI  - Overlapping sphincteroplasty for acquired anal incontinence.
AB  - Overlapping sphincter repair is the operation of choice for incontinence due to
      obstetric injuries, trauma, or previous anorectal surgery. We present our
      experience from 1981 to 1990 using the overlapping sphincter repair for anal
      incontinence resulting from childbirth in 21 patients (58%), previous anorectal
      surgery in 7 (19%), trauma in 1 (3%), gynecologic surgery in 1 (3%),
      multifactorial causes in 1 (3%); the incontinence was idiopathic in 5 (14%). All
      36 patients were operated on by one surgeon and had identical care. There were no
      deaths. Two patients required colostomy for wound sepsis. Two additional patients
      (with idiopathic incontinence) elected to have a colostomy after failure of
      sphincter repair. Long-term follow-up was possible in 33 patients (92%). Twenty
      four patients (73%) were considered to have good to excellent results.
      Eliminating those patients with idiopathic anal incontinence improved the results
      significantly. Twenty-two patients (85%) reported good to excellent results.
      Twenty-four patients (92%) consider their continence better now than before
      surgery and 25 patients (96%) would undergo the procedure again. In conclusion,
      overlapping sphincteroplasty has a definite role in treatment of anal
      incontinence due to obstetric injury, anorectal surgery, and trauma, but a more
      limited role in treatment of idiopathic anal incontinence.

PMID- 8272916
TI  - Stereotactic brain biopsy for diagnosis of progressive multifocal
      leukoencephalopathy.
AB  - We describe three patients in whom the diagnosis of progressive multifocal
      leukoencephalopathy (PML) was made by stereotactic biopsy. All three patients had
      a rapidly progressive clinical course pathologically characterized by
      demyelination, Alzheimer I astrocytes, and basophilic intranuclear inclusions in
      oligodendrocytes. In each case, the diagnosis was confirmed with
      immunohistochemical staining of oligodendrocytes for the JC virus and in one case
      by electron microscopy. Determination of the adequacy of tissue received at the
      time of frozen section is critical and can direct the appropriate submission of
      tissue to maximize available diagnostic procedures.

PMID- 8272917
TI  - Effect of citrate on serum aluminum concentrations in hemodialysis patients: a
      prospective study.
AB  - Twenty hemodialysis patients were prospectively evaluated to determine if
      concomitant citrate and aluminum administration enhances the absorption of
      aluminum, thereby increasing the possibility of toxicity. The four-phase study
      consisted of phase I, a washout phase; phase II, an aluminum treatment phase;
      phase III, a treatment phase combining aluminum and soluble calcium citrate; and
      phase IV, a treatment phase with the patient's original prestudy phosphate
      binder. Results disclosed a progressive rise in serum aluminum levels
      (microgram/L) from 47 +/- 8 (phase I) to 62 +/- 12 (phase II) to 74 +/- 13 (phase
      III) and a drop to 58 +/- 12 (phase IV). The difference in levels between phases
      I and III was significant. Additionally, and despite the fact that serum calcium
      concentrations did not change, serum phosphate and immunoreactive parathyroid
      hormone concentrations were significantly lower when aluminum and citrate were
      used together. This suggests that citrate enhances the absorption of aluminum and
      therefore increases the possibility of toxicity in the patient with end-stage
      renal disease.

PMID- 8272918
TI  - The German health care system: model or mirage?
AB  - Rising costs have spurred America's leaders to look abroad for a model upon which
      to pattern reform of our health care system. On the surface, at least, Germany
      would appear to have an ideal system combining universal access, high quality,
      free choice of physicians, and cost control. Germany has been particularly
      effective in curbing pharmaceutical and administrative expenses, and has avoided
      the progressive imbalance between primary care providers and medical specialists
      seen in America. However, Germany lags behind the US in emphasizing preventive
      services and in shifting services to the ambulatory setting. Also, an oversupply
      of physicians, lack of incentives to limit the volume of services, and a global
      budget cap have combined to induce physicians to do more while their incomes were
      falling sharply relative to those of other workers. Although selected elements of
      the German health care system could be beneficial to America, full-scale adoption
      of the German system is neither realistic nor desirable.

PMID- 8272919
TI  - Autoimmune hypothyroidism in a patient with generalized resistance to thyroid
      hormone.
AB  - Generalized resistance to thyroid hormone is a rare condition; affected
      individuals have elevated serum levels of free thyroxine and free
      triiodothyronine with inappropriately normal or slightly elevated levels of
      thyrotropin, yet are generally clinically euthyroid. However, responsiveness to
      thyroid hormone varies from tissue to tissue, and some patients may benefit from
      treatment with exogenous hormone. We have described the case of a patient with
      this disorder who initially had a mildly elevated serum thyrotropin level and was
      clinically euthyroid but in whom symptomatic autoimmune hypothyroidism
      subsequently developed. The serum free thyroxine level, although diminished from
      its previously elevated value, remained within the normal range. The patient
      required substantial doses of levothyroxine to return basal and stimulated TSH to
      their prior levels. Criteria for the treatment of adults with this disorder have
      not been firmly established. This case suggests that one indication for thyroid
      hormone supplementation may be the presence of high-titer serum antithyroid
      antibodies in patients who initially have mildly elevated thyrotropin values;
      they could be at increased risk for progression to overt hypothyroidism.

PMID- 8272920
TI  - Inadvertent puncture of the urinary bladder by a peritoneal dialysis catheter.

PMID- 8272921
TI  - Elevated parathyroid hormone-related protein and hypercalcemia in a patient with
      cutaneous squamous cell carcinoma complicating hidradenitis suppurativa.
AB  - We have described the case of a patient with long-standing hidradenitis
      suppurativa in whom associated cutaneous squamous cell carcinoma developed; this
      was complicated by hypercalcemia. Serum PTH-RP levels were elevated to 14.8
      pmol/L. This is the third case report of hypercalcemia associated with squamous
      cell carcinoma complicating hidradenitis suppurativa and the first in which an
      elevated serum PTH-RP level has been documented in cutaneous squamous cell
      carcinoma.

PMID- 8272922
TI  - Achalasia mistakenly diagnosed as eating disorder and prompting prolonged
      psychiatric hospitalization.
AB  - We have reported a rather extreme instance in which achalasia was misdiagnosed as
      a primary eating disorder. Our patient spent 2 months in a psychiatric
      institution before the correct diagnosis was made. Misdiagnosis in this case
      could have been avoided (1) if the symptoms of dysphagia had been elicited as
      part of her history, (2) if it had been recognized that the vomiting (her
      dominant symptom) was involuntary and not self-induced, (3) if the absence of
      disturbed body image had been appreciated, or (4) if it had been recognized that
      she did not meet accepted criteria for anorexia nervosa or bulimia. Our case and
      others like it in the literature also illustrate that achalasia frequently
      remains an elusive diagnosis.

PMID- 8272923
TI  - Saccular aortic aneurysm causing complete distal esophageal obstruction.
AB  - We have reported a case of progressive dysphagia and complete esophageal
      occlusion due to a saccular aortic aneurysm. Aortic aneurysm should be an initial
      consideration in the differential diagnosis and investigation of dysphagia.
      Complete esophageal occlusion is a rare and late manifestation of a saccular
      thoracic aortic aneurysm and has been fatal in two of the three reported cases.
      Prompt preoperative diagnosis and aortic repair has not yet been reported.

PMID- 8272924
TI  - L-carnitine as a treatment for Rett syndrome.
AB  - A 17-year-old girl with Rett syndrome, who was taking no other medications, was
      treated with L-carnitine (50 mg/kg/day). Within 2 months of initiation of
      treatment, she became much more alert, developed good eye contact, started
      reaching for objects with both hands, and answered simple questions with one or
      two words. L-carnitine was discontinued and within 1 week she lapsed into her
      pretreatment condition of lethargy with no interest in her environment, not
      reaching for objects, poor eye contact, and not speaking. One week after L
      carnitine was resumed, she again became alert, started reaching for objects, and
      saying one or two words. Her serum carnitine levels (free and total) were within
      normal limits before and after L-carnitine treatment, but were higher while she
      was taking L-carnitine. Her serum ammonia was within normal limits prior to
      starting L-carnitine. L-carnitine appears to be an effective treatment for this
      girl with advanced Rett syndrome.

PMID- 8272925
TI  - Unusual cutaneous adverse reaction to warfarin therapy.
AB  - We have described a patient who had an extensive maculopapular pruritic rash
      after a single dose of warfarin. Although dermatologic reactions have been
      reported with this drug, the pathogenesis of these reactions remains unknown.

PMID- 8272926
TI  - Ribavirin and intravenous immune globulin therapy for measles pneumonia in HIV
      infection.
AB  - We have described a patient, immunocompromised from an infection with the human
      immunodeficiency virus, who had rapidly progressive measles complicated by
      measles pneumonia and respiratory failure. Rapid improvement in the patient's
      condition followed therapy with inhaled ribavirin and intravenous immune
      globulin. Patients who have measles pneumonia associated with respiratory failure
      may benefit from combination therapy with ribavirin and IV immune globulin.

PMID- 8272927
TI  - Large asymptomatic carcinoid tumor in an HIV-infected man.
AB  - Many different tumor types have been described in patients with AIDS; carcinoid
      tumors, however, are a distinct exception to this phenomenon. Our case
      illustrates the asymptomatic presentation of a large abdominal carcinoid in an
      HIV-infected man, and further expands the list of neoplasms that have been found
      in this population.

PMID- 8272928
TI  - NSAID nephrotoxicity revisited: acute renal failure due to parenteral ketorolac.
AB  - The success of ketorolac as a nonnarcotic analgesic is likely to propagate its
      widespread use to control moderate to severe postoperative pain. Indeed, of the
      patients treated with ketorolac and described in the medical literature, nearly
      90% had had a major surgical procedure. Since any such procedure may be
      associated with significant third-spacing of the fluid and result in renal
      hypoperfusion, care must be taken in administering ketorolac. Close attention to
      urine output and parameters of renal function must be maintained. Moreover,
      postoperative ketorolac therapy should be avoided in patients who have conditions
      that predispose to NSAID nephrotoxicity (as in our Case 1). Likewise, in
      nonsurgical patients the same degree of caution should be used with ketorolac as
      with any oral NSAID. Finally, since ketorolac is excreted almost entirely by the
      kidney, either elderly patients or patients with underlying renal insufficiency
      must have an adjustment of the dosing interval, or this medication should be
      avoided in such patients altogether.

PMID- 8272929
TI  - Multiple Beau's lines in a patient with fever of unknown origin.
AB  - We describe a case of fever of unknown origin (FUO) of 9 months' duration in
      which the finding of regularly spaced multiple Beau's lines (the "ladder nail"
      sign) pointed to the possibility of a relapsing fever of the Pel-Ebstein variety
      and an underlying lymphoma. Subsequent investigation confirmed the association of
      the Beau's lines and fever, as well as the diagnosis of Hodgkin's disease as the
      cause of the FUO. In this setting, Beau's lines may provide an important
      diagnostic clue and should be carefully looked for on physical examination.

PMID- 8272930
TI  - Toxic shock syndrome mimicking pelvic inflammatory disease presumably resulting
      from tattoo.
AB  - The female patient with a variety of genital tract symptoms offers a distinct
      challenge to the gynecologist. We report a case that on initial examination was
      thought to be pelvic inflammatory disease (PID). After further evaluation, our
      patient was found to be suffering from toxic shock syndrome, which in many ways
      may resemble PID. This case demonstrates the importance of a careful and thorough
      evaluation of the gynecologic patient who has several nonspecific signs and
      symptoms.

PMID- 8272931
TI  - Angiotropic lymphoma manifested by fever and painful swollen legs.
AB  - In summary, angiotropic lymphoma is generally of B-cell origin and can be
      manifested by isolated cutaneous lesions. More commonly, however, the disease
      involves the CNS. Angiotropic lymphoma should be included in the differential
      diagnosis of patients with clinical features of panniculitis or diffuse
      multisystem vasculitis.

PMID- 8272932
TI  - Renal infarction associated with cocaine use and latent protein C deficiency.
AB  - We have described the case of a patient with a renal thrombosis and renal
      infarction associated with cocaine use and protein C deficiency. We propose that
      patients with similar presentations receive a thorough evaluation for a
      hypercoagulable state, including protein C levels. Once the diagnosis is made,
      immediate intervention is required to protect renal function.

PMID- 8272933
TI  - Apparent culture-negative endocarditis of the prosthetic valve caused by
      Cardiobacterium hominis.
AB  - To date, there have been fewer than 50 reported cases of endocarditis caused by C
      hominis. Only six of these involved prosthetic heart valves. To our knowledge, in
      no previous case has the organism been cultured directly from the valve, an
      aspect we believe gives our case special relevance. Our case also illustrates the
      fact that whenever a fastidious organism is thought to be responsible for
      infective endocarditis, not only blood cultures but also cardiac tissue cultures
      should be held beyond the customary period of time.

PMID- 8272934
TI  - Melanoma matters.

PMID- 8272935
TI  - Chemotherapy-induced alopecia.

PMID- 8272936
TI  - Multicentric granular cell tumors.

PMID- 8272938
TI  - Cervical Spine Research Society. 20th Annual Meeting, Palm Desert, California,
      December 3-5, 1992. Proceedings.

PMID- 8272937
TI  - Tentacle elbow (to replace tennis elbow)

PMID- 8272939
TI  - Surgically related upper cervical spine canal anatomy in children.
AB  - MRI studies of the upper spines of 121 children were evaluated to precisely
      define the sagittal anatomy at C1 in the pediatric population. The diameters of
      the spinal cord, bony canal, space available for the cord (SAC), dens+atlanto
      dens interval (ADI), and "free" space were measured. The results demonstrate an
      accelerated growth in the C1 canal, dens + ADI, and SAC during the first four
      years after birth. Steel's rule of thirds was shown to roughly hold true
      throughout childhood. Neonates have an average SAC diameter of 12.4 mm, a value
      less than the 13 mm dimension commonly used to define relative stenosis in
      children.

PMID- 8272940
TI  - The trabecular anatomy of the axis.
AB  - This article describes the internal anatomy of C2. Although some C2 specimens
      showed a high density of trabecular bone throughout, a feature noted in all
      specimens was a void or very hypodense area of bone located immediately beneath
      the dens. The observed nonuniform distribution of trabecular bone within the axis
      is considered to have an effect on internal fixation of this bone. The good
      cancellous bone quality consistently observed in the lateral masses and beneath
      the facets, as well as near the bony end plates, suggests that these areas may be
      reasonable sites for the insertion of internal fixation devices. The hypodense
      area observed in the upper portion of C2 would suggest that fixation devices
      inserted through this area may obtain relatively poor purchase and may be prone
      to cut-through failure.

PMID- 8272941
TI  - Biomechanics of odontoid fracture fixation. Comparison of the one- and two-screw
      technique.
AB  - Direct anterior screw fixation of odontoid fractures has become more prevalent
      clinically. No biomechanical study, however, has determined whether one or two
      screws should be used. This study measured the stability of the odontoid process
      after fracture and internal fixation with one or two screws. Internal fixation of
      Type II odontoid fractures did not restore the original stability of the intact
      specimen, direct internal fixation with one or two screws provided 50% of the
      stability of the unfractured odontoid, and no significant differences between the
      one- and two-screw technique was found under loading to failure, although the two
      screw technique provided increased stiffness in extension loading.

PMID- 8272942
TI  - Atypical hangman's fractures.
AB  - Nineteen cases of traumatic spondylolisthesis of the axis, including 13 standard
      hangman's fractures and 6 anterolistheses of the C2 vertebral body associated
      with Effendi's atypical hangman's fractures, were studied. Unlike the standard
      Effendi Type I or Type II fractures, atypical hangman's fractures, occurring
      through the posterior aspect of the vertebral body with unilateral or bilateral
      continuity of the posterior cortex or pedicle, routinely narrow the spinal canal
      because of the fracture pattern and degree of subluxation. These atypical C2
      injuries were more frequent and more often accompanied by paralysis (33%) than
      was previously anticipated. Because of their greater potential for neurologic
      compromise, it is essential that these fractures be recognized as distinct from
      standard Types I and II C2 fractures. Larger series should clarify both the true
      incidence of paralysis and long-term results from these unique C2 injuries.

PMID- 8272943
TI  - Predictability of operative results of cervical compression myelopathy based on
      preoperative computed tomographic myelography.
AB  - The transverse area and flattening ratio of the spinal cord were determined with
      preoperative computed tomographic myelography in 103 patients with cervical
      compression myelopathy: cervical spondylotic myelopathy (n = 44); ossification of
      the posterior longitudinal ligament (n = 39); and cervical disc herniation (n =
      20). With these values and other clinical items (eg, age, duration of symptoms,
      preoperative severity), a linear model to predict postoperative recovery was
      attempted by multiple regression analysis. In cervical spondylotic myelopathy and
      ossification of the posterior longitudinal ligament, the transverse area of the
      spinal cord and the duration of symptoms were accepted as effective explanatory
      variables to predict recovery. In cervical disc herniation, regardless of the
      transverse area or duration, the recovery was good, and pathologic state was
      considered essentially different.

PMID- 8272944
TI  - Dissociated motor loss in the upper extremities. Clinical features and
      pathophysiology.
AB  - Dissociated motor loss occurring in the upper extremities with and without lower
      extremity myelopathy was evaluated in patients with cervical spondylosis. The
      presence of dissociated motor loss without attendant myelopathy was correlated
      with selected compression of the anterior nerve root in the lateral spinal canal,
      close to the intervertebral foramen. The clinical and radiologic feature
      differentiating these two dissociative syndromes were reviewed.

PMID- 8272945
TI  - Anterior surgery in four consecutive technical phases for cervical spondylotic
      myelopathy.
AB  - Between 1960 and 1990, 175 patients having anterior operations for cervical
      spondylotic myelopathy were evaluated during the course of four operative phases.
      Specific attention was paid to spine and spinal cord morphologic changes
      occurring in 52 patients, who were followed up for more than 12 years. Although
      overall outcomes were satisfactory, a disturbing incidence of neurologic
      deterioration caused by spondylolisthesis at levels adjacent to fused segments,
      kyphosis, and altered cord morphology was noted 10 years after surgery. These
      changes, observed in patients with multilevel pathology and a narrowed spinal
      canal, promoted the adoption of more stringent operative criteria, including
      ultrasonically confirmed 16-mm or greater anterior trough decompressions and the
      performance of long fusions with vascularized fibular struts.

PMID- 8272946
TI  - Anterior cervical discectomy, fusion, and plating. A comparative animal study.
AB  - Thirty-five goats were used as animal models for three-level anterior cervical
      discectomy and fusion. The goats were divided equally into five experimental
      groups: Group I, three-level anterior cervical discectomy without fusion; Group
      IIa, three-level discectomy with autogenous bone (Smith-Robinson technique);
      Group IIb, autogenous bone grafting plus anterior plate application; Group III,
      three-level discectomy and fusions with fresh frozen allograft bone; Group IIIa,
      graft only; and Group IIIb, anterior plating. The goats were killed, and spines
      were removed and analyzed for evidence of fusion. Radiographic union was judged
      to have occurred in 0% of Group I disc spaces, 48% of Group IIa, 52% of Group
      IIb, and 38% of Groups IIIa and IIIb. Histologic fusion was judged to have
      occurred in 0% of Group I specimens, 38% of Group IIa, 45% of Group IIb, 0% of
      Group IIIa, and 19% of Group IIIb. The histologic fusion rate was significantly
      higher in Groups IIa and IIb than in Groups I and IIIa. There was no
      statistically significant increase in the histologic fusion rate between goats
      with anterior cervical plating and goats without plating. Biomechanically, the
      spines in Groups IIb and IIIb, ie, those with anterior plates applied, were
      stiffer in axial load, torsion, and flexion/extension. Peri-end-plate vascularity
      was significantly diminished in those groups that had anterior plates applied.
      Qualitative analysis of fluorochrome labels showed that autografts revascularized
      more rapidly than did allografts in both the nonplated and plated groups.
      Histomorphometric analysis failed to reveal any significant device-related
      osteopenia in those vertebrae spanned by the anterior plate. We found that
      although autograft bone led to a significantly higher rate of union than did
      allograft bone, the addition of anterior plate fixation did not significantly
      increase union rate. Biomechanical rigidity was significantly increased in all
      modes of testing by the use of an anterior plate. The decreased vascular response
      seen in spines that underwent plating may be responsible for the lack of
      increased union. The increased rigidity found with anterior plating supports its
      use in traumatic conditions. The failure, however, to increase significantly the
      union rate in this model fails to lend support to the use of anterior cervical
      plating for degenerative discectomy and fusion procedures.

PMID- 8272947
TI  - Occipitocervical arthrodesis using contoured plate fixation. An early report on a
      versatile fixation technique.
AB  - A simple, inexpensive, and rigid technique for occipitocervical fixation was
      evaluated in 14 patients with occipitocervical instability. Posterior arthrodeses
      of the occipitocervical region were performed using pelvic reconstruction plates
      and screws as internal fixation devices. At follow-up, which averaged 11.7
      months, all patients had fused with minimal complications. This versatile
      technique, readily adapted to complex deformities and extensible for subaxial
      fixation, was reviewed.

PMID- 8272948
TI  - A biomechanical evaluation of magnetic resonance imaging-compatible wire in
      cervical spine fixation.
AB  - In a bovine cervical spine model, the ultimate and fatigue strengths as well as
      relative magnetic resonance imaging artifact produced by titanium, cobalt chrome,
      and stainless-steel wires in various gauges were assessed. Single-cycle and
      fatigue strength of wire constructs were measured. Although larger wires
      generally had greater static strength, fatigue strength was mixed. Sixteen-gauge
      titanium, and all stainless-steel models (22-gauge braided, 18-gauge, and Songer
      cable) withstood 10,000 cycles without failure, whereas all other constructs
      rarely could withstand a similar 10,000 cycles. Magnetic resonance imaging was
      performed on calf cervical spines instrumented with the various materials.
      Titanium exhibited the least artifact, stainless-steel showed the greatest
      artifact, and cobalt chrome an intermediate amount. Although titanium wire
      produces the least amount of magnetic resonance imaging artifact, it remains a
      poor choice for implant fixation because its notch sensitivity reduces its
      fatigue resistance compared with stainless steel, which remains the more
      dependable choice.

PMID- 8272949
TI  - A biomechanical comparison of cervical laminaplasty and cervical laminectomy with
      progressive facetectomy.
AB  - The effects of multilevel cervical laminaplasty and laminectomy with increasing
      amounts of facetectomy on stability of the cervical spine were tested with
      physiologic loading in nine cadaveric specimens. Cervical spines, levels C2-C7,
      were tested with physiologic loading in a constraint-free test system, the motion
      of each body being tracked in a three-dimensional coordinate system. Cervical
      laminectomy with 25% or more facetectomy resulted in a highly significant
      increase in cervical motion compared to the intact specimens for the dominant
      motions of flexion/extension (P < 0.003), axial torsion (P < 0.001), and lateral
      bending (P < 0.001). Cervical laminaplasty was not significantly different from
      the intact control, except for a marginal increase in axial torsion. Coupled
      motion did not change with laminaplasty or laminectomy with progressive
      facetectomy. As little as 25% facetectomy adversely affects stability after
      multilevel cervical laminectomy. Cervical laminaplasty avoids this problem, while
      still affording multilevel decompression. Therefore in patients undergoing
      cervical laminectomy accompanied by more than 25% bilateral facetectomy,
      concurrent arthrodesis should be performed.

PMID- 8272950
TI  - Cervical stability after sequential capsule resection.
AB  - A portion of the cervical facet joint must be resected to expose and decompress
      cervical nerve roots from a posterior approach. When posterior fusion is
      performed, it is common to remove the facet capsule only for the joints being
      fused. This study was performed to examine the effect of resection of the facet
      capsule alone, without disruption of the bony facet to determine what degree of
      facet-capsule resection leads to acute instability. Seven human cervical
      cadaveric spines were used in the experiment. Nondestructive biomechanical
      testing was performed in axial load, flexion, extension, and torsion. Each
      specimen was tested intact and after sequential resection of 25%, 50%, 75%, and
      100% of the C5-6 facet capsules. Axial stiffness changed very little during the
      experiment. In torsion, the displacement increased 1% after a 25% capsule
      resection, 19% after a 50% resection, and 25% after a 75% or 100% resection. No
      gross subluxation was seen during the torsional test. In the flexion test,
      posterior displacement increased 4% after a 25% resection, 5% after a 50%
      resection, 32% after a 75% resection, and 22% after a 100% resection. There was a
      statistically increased displacement seen during the flexion test after 75% or
      100% of capsule resection. Thus, significant hypermobility did occur during both
      torsion and flexion testing with greater than 50% resection of the facet
      capsules. Great care should be taken when exposing an unfused facet to limit
      facet-capsule resection to less than 50%. With resection of greater than 50% of
      the capsule, postoperative hypermobility can occur and may require stabilization.

PMID- 8272951
TI  - The pathomechanics of compression injuries in the cervical spine. Nondestructive
      and destructive investigative methods.
AB  - Biomechanical analysis using nondestructive and destructive investigative methods
      was performed to evaluate the mechanisms of cervical compression injuries. These
      injuries produce two basic modes of failure: 1) anterior dislocation; and 2)
      rupture of the anterior ligamentous complex of the vertebral body. Distribution
      of these two failure patterns was determined by the initial cervical spine
      position; translational alignment did not have a significant effect. Different
      results were observed between spines positioned in flexion and extension,
      indicating that the most important factor determining the mode of failure was
      rotational alignment in the sagittal plane.

PMID- 8272952
TI  - A methodology to evaluate motion of the unstable spine during intubation
      techniques.
AB  - Airway management in patients with an unstable cervical spine remains a
      challenge. A video fluoroscopic technique that transfers the image to a floppy
      disk for direct measurement is described. This technique enabled standardized,
      direct measurement of the cervical spine during airway maneuvers before and after
      a C5-6 posterior instability was surgically created in five cadaveric specimens.
      Unsupported direct oral techniques often can cause more motion than do indirect
      nasal techniques, and chin lift/jaw thrust and cricoid pressure can cause as much
      motion as do some of the intubation techniques.

PMID- 8272953
TI  - Magnetic resonance imaging study on the results of surgery for cervical
      compression myelopathy.
AB  - The morphologic changes and signal intensity of the spinal cord on preoperative
      magnetic resonance images were correlated with postoperative outcomes in 74
      patients undergoing decompressive cervical surgery for compressive myelopathy.
      The transverse area of the spinal cord on T1-weighted images at the level of
      maximum compression was closely correlated with the severity of myelopathy,
      duration of disease, and recovery rate as determined by the Japanese Orthopaedic
      Association score. In patients with ossification of the posterior longitudinal
      ligament or cervical spondylotic myelopathy, the increased intramedullary T2
      weighted magnetic resonance imaging signal at the site of maximal cord
      compression and duration of disease significantly influenced the rate of
      recovery. A multiple regression equation was then developed with these three
      variables to predict surgical outcomes.

PMID- 8272954
TI  - Magnetic resonance imaging study of experimental acute spinal cord injury.
AB  - Magnetic resonance imaging (MRI) has been used widely in the diagnosis of acute
      spinal cord injuries. The association between MRI findings and histologic
      changes, however, remains unclear. Using a rabbit spinal cord injury model, the
      authors compared the MRI and histologic abnormalities as they evolved over the
      first post-trauma month. Bleeding in the gray matter, visualized as a low
      intensity area on T1-weighted views and high-intensity area on T2-weighted views,
      observed immediately after injury, disappeared within the first week. Edema,
      appearing 6 hours after the initial injury and seen as a high-intensity T2
      weighted MRI image, became maximal 1 week later and gradually decreased
      thereafter. Also appearing 1 week later, were necrotic changes in the gray
      matter, corresponding to low signals on T1-weighted studies but high signals on
      T2-weighted studies. MRI therefore helped differentiate hemorrhage and necrosis,
      presumably irreversible lesions, from the more reversible findings related to
      edema.

PMID- 8272955
TI  - Cervical discography complications and clinical efficacy.
AB  - To determine the incidence and magnitude of complications of cervical discography
      as well as to assess the clinical results of operative treatment based on
      discographic findings, a series of 31 patients who underwent cervical discography
      was reviewed. Twenty-six patients (84%) experienced provocative concordant
      symptomatology and were considered positive. The overall complication rate was
      13% (4/31), including the development of an acute epidural abscess that led to
      myelopathy and eventual quadriplegia. Of the twenty-two patients who underwent
      anterior cervical discectomy and fusion on the basis of cervical discography, one
      patient had an excellent result (5%), nine patients had good results (41%), and
      six patients each had fair and poor results (54%). Diagnostic cervical
      discography was found not to provide the degree of clinical predictive value
      necessary to substantiate its potential risks and complications.

PMID- 8272956
TI  - Penetration of glycopeptide antibiotics in nucleus pulposus.
AB  - The penetration of the glycopeptide antibiotics vancomycin and teicoplanin into
      the nucleus pulposus of rabbits was studied. Blood samples were obtained at 0.5,
      1, 4, 8, and 24 hours after intravenous administration of 30 mg/kg vancomycin or
      16 mg/kg teicoplanin. Concentrations of antibiotics were determined in tissue
      specimens and serum samples by fluorescence polarization immunoassays.
      Antimicrobial activity in the nucleus pulposus was determined with an agar
      diffusion method using a strain of Micrococcus luteus as the indicator organism.
      A peak concentration of vancomycin in the nucleus pulposus was attained 8 hours
      after drug administration. Teicoplanin reached its maximum level and plateaued 1
      and 2 hours, respectively, after injection, and it remained unchanged for the
      rest of the study. This microbiologic analysis showed that the nucleus pulposus
      contained an antimicrobial level of glycopeptide antibiotics after
      administration. Because rabbit nucleus pulposus is similar anatomically to that
      of humans, these results may have implications regarding the timing and choice of
      antibiotic administration.

PMID- 8272957
TI  - Ideal thickness of Smith-Robinson graft for anterior cervical fusion. A cadaveric
      study with computed tomographic correlation.
AB  - To establish the optimal thickness for Smith-Robinson anterior cervical fusion
      grafts, anterior C4-5 discectomy and fusions were performed on six fresh, frozen
      cadavers. Plain radiographs and computed tomographic scans then were employed to
      correlate graft placement with changes in disc space height, foraminal height,
      and foraminal areas after 3-, 5-, 7-, and 9-mm interbody fusions. The ideal graft
      thickness appeared to be directly related to the preoperative baseline disc
      height. For a preoperative disc height of 3.5-6.0 mm, an interbody graft of 2 mm
      above baseline thickness was most appropriate. A thicker graft was required when
      the baseline disc height was smaller (2.0 mm) and a thinner graft when the disc
      height was larger (7.4 mm). No significant correlation was noted between disc
      space distraction at C4-5 and disc height, foraminal height, or foraminal area at
      adjacent levels.

PMID- 8272958
TI  - Iliac crest bone graft. Osteotome versus saw.
AB  - The strength of saw-harvested vs. osteotome-harvested Smith-Robinson iliac crest
      grafts from five fresh frozen cadavers was compared. Matched pairs of grafts were
      harvested, one with a saw and the other with an osteotome from equivalent
      locations on the two iliac crests of each pelvis. Grafts were tested to failure
      in axial compression, and load-displacement curves were recorded for each test.
      Yield load and displacement, ultimate load, and stiffness were calculated, and
      statistical analysis was performed with the Student t test and three-way analysis
      of variance. Evaluation of the 66 pairs of grafts revealed that saw-harvested
      grafts were consistently stronger than were matched grafts harvested with an
      osteotome. The middle third of the iliac crest produced significantly stronger
      grafts, and those harvested from younger donors were significantly stronger than
      those obtained from older donors. Of even greater clinical relevance, saw
      harvested grafts were stiffer than osteotome-harvested grafts. Based on these
      findings, it is recommended that iliac crest grafts harvested for spine fusion be
      obtained with an oscillating saw rather than with an osteotome.

PMID- 8272959
TI  - Pain and the nerve root. An interdisciplinary approach.
AB  - Based on the experimental and clinical results in the literatures and the
      author's experience, a working hypothesis for the pathomechanism of radicular
      pain is proposed. When the nerve root is involved, mechanical and circulatory
      changes are produced. Inflammatogenic materials may leak from the degenerative
      disc and facet into the nerve root, causing chemical radiculitis. These changes
      can be followed by nerve fiber and cell changes including blockage of axonal flow
      and demyelination, causing ectopic discharges and cross talk. Disturbed or
      enhanced synthesis and transport of neuropeptides can also be elicited. These
      multifactorial changes may finally result in sensitization of both the central
      and peripheral nervous systems, causing radicular pain.

PMID- 8272960
TI  - Monitoring of lumbosacral nerve roots during spinal instrumentation.
AB  - A technique is described for intraoperative, multimodality electrophysiologic
      monitoring of the spinal cord and lumbosacral nerve roots (cauda equina).
      Simultaneous monitoring with the techniques of electromyography, compound muscle
      action potentials, and somatosensory evoked potentials is found to provide highly
      useful information to the surgeon during lumbar spine instrumentations. Compound
      muscle action potential recordings are used to identify nerve roots in the
      lumbosacral region, especially when visual identification of the nerve is
      hindered by scarring or distortion of the anatomy. Electromyography continuously
      monitors nerve roots at risk by revealing neurotonic discharges when the nerve
      roots are irritated during surgical dissection or placement of the fixation
      device. The early warning provided by this technique enables the surgeon to avoid
      irreversible neurologic damage.

PMID- 8272961
TI  - Percutaneous nucleotomy in lumbar disc herniation. A prospective study.
AB  - The purpose of this article is to present the clinical results of the prospective
      series of studies on percutaneous nucleotomy (PN) for lumbar disc herniation and
      to introduce current criteria of patient selection for PN. Since 1983, 107
      patients were treated with PN (Hijikata's method), 85 of whom had a follow-up
      period of more than 2 years. Of these 85 patients, 54 had successful results.
      Clinical findings and various imaging evaluations (eg, magnetic resonance imaging
      and computed tomography after discography) before PN, as well as operative
      findings, were used to study the surgical outcomes of both the successful and
      unsuccessful groups. The results yielded the following new criteria for patient
      selection for PN: 1) age less than 40 years; 2) no perforation of the posterior
      longitudinal ligament and no degenerative canal stenosis detected by computed
      tomography after discography; 3) no malformation of the neural structure; 4) more
      than Grade 4 on manual testing of innervated muscles; and 5) more than 6 months
      of conservative treatment before PN.

PMID- 8272962
TI  - Nine-year mean follow-up of one-stage anteroposterior excision of hemivertebrae
      in the lumbosacral spine.
AB  - Six patients with lumbosacral hemivertebrae were treated by one-stage anterior
      and posterior excision of the hemivertebrae. Long-term follow-up is reported.
      Overall, correction of the lumbosacral curve was 46%, including one case of
      pseudarthrosis and subsequent loss of correction. More importantly, truncal
      imbalance was restored unless other congenital thoracic anomalies were present.
      New methods of calculating rib cage shift on the pelvis as well as vertebral
      column displacement from the sagittal plane are presented.

PMID- 8272963
TI  - The natural history of radiographic instability of the lumbar spine.
AB  - The natural history of radiographic instability of the lumbar spine was
      determined by reexamination of 50 patients who had been diagnosed with this
      condition at least 10 years previously and correlation of these findings with
      changes in the clinical condition. The initial diagnosis and follow-up
      examination was performed by dynamic radiography, and the following observations
      were made: 1) radiographic instability resolved spontaneously in 20% of cases; 2)
      radiographic instability due to isolated posterior opening (asymmetric anterior
      collapse of the intervertebral disc in flexion) usually was self-limited; and 3)
      combined posterior opening and forward translation in flexion was associated with
      chronic instability and debilitating symptoms. The functional prognosis, whether
      or not symptoms are improved, in patients with radiographic lumbar instability
      depends primarily on developmental narrowing of the spinal canal, rather than on
      the existence or type of radiographic instability.

PMID- 8272964
TI  - Early stabilization and decompression for incomplete paraplegia due to a thoracic
      level spinal cord injury.
AB  - All patients treated between 1985 and 1990 for acute incomplete spinal cord
      injury between T2 and T11 were retrospectively studied. This level was chosen for
      study because by excluding cervical cord, conus, and cauda equina injuries,
      neurologic improvement could be attributed to improvement of spinal cord
      function. Only 14 patients with incomplete thoracic level paraplegia were
      identified, representing 1.2% of all spinal injuries. All 14 patients were
      treated by early operative reduction, stabilization, or decompression. Twelve
      patients had surgery within 24 hours of neurologic injury, one at 36 hours, and
      one at 5 days. Twelve patients had initial posterior instrumentation and fusion,
      one of whom subsequently had an anterior decompression. Two patients had initial
      anterior decompression and fusion. Both later had posterior instrumentation and
      fusion to treat progressive deformity. Follow-up averaged 20 months (range, 9-65
      months). Neural function before surgery and at follow-up was given a Frankel
      grade and lower extremity motor index score. Of 13 surviving patients, seven were
      initially Frankel B and six Frankel C. Of the seven patients initially Frankel B,
      four recovered to Frankel E, two improved to Frankel D, and one remained Frankel
      B. Of the six patients originally Frankel C, five recovered to Frankel E and one
      improved to Frankel D. Average neurologic improvement was 2.2 Frankel grades per
      patient, lower extremity motor index improved from an average of 7 to 44. Early
      surgical reduction, stabilization, and decompression is safe and improves
      neurologic recovery in comparison to historical controls treated by postural
      reduction or late surgical intervention.

PMID- 8272965
TI  - Finite-element stress analysis of the normal and osteoporotic lumbar vertebral
      body.
AB  - A finite-element model of an isolated elderly human L3 vertebral body was
      developed to study how material properties and loading conditions influence end
      plate and cortical-shell displacements and stresses. The model consisted of an
      idealized geometric representation of an isolated vertebral body, with a 1-mm
      thick end plate and cortical shell. For uniform compression, large tensile
      stresses occurred all around the cortical shell just below the end plate as a
      result of bending of the cortical shell as it supported the end plate. Large
      tensile bending stresses also developed in the inferior surface of the end plate.
      Equal reductions in both trabecular and cortical bone moduli increased
      displacements but did not affect peak stresses. A 50% reduction in trabecular
      bone modulus alone increased peak stresses in the end plate by 74%. Elimination
      of the cortical shell reduced peak stresses in the end plate by approximately
      20%. For nonuniform, anteriorly eccentric compression, peak stresses everywhere
      changed by less than 11% but moved to the anterior aspect. When material
      properties were adjusted to represent osteoporosis with disproportionate
      reductions in trabecular (50% decrease) and cortical (25% decrease) bone moduli,
      anterior compression increased peak stresses by up to 250% compared to uniform
      compression. If fractures are initiated in regions of large tensile stresses, the
      results from this relatively simple model may explain how central end-plate and
      transverse fractures initiate from uniform compression of the end plate.
      Furthermore, for anterior compression, disproportionate modulus reductions in
      trabecular and cortical bone may substantially increase end plate and cortical
      shell stresses, suggesting a cause of age-related spine fractures.

PMID- 8272966
TI  - The development of response strategies in preparation for sudden loading to the
      torso.
AB  - Sudden and unexpected loading to the torso has been reported in the literature as
      a potential cause of low-back disorders. When such loadings occur, it is
      hypothesized that the body's response is designed to minimize the destabilizing
      postural disturbance, and to minimize the mechanical loading of the
      musculoskeletal system. This study tested hypotheses regarding the role of task
      experience in the development of preparatory strategies that potentially minimize
      the postural disturbance to the body and minimize the mechanical loading of the
      spine. These strategies were hypothesized to consist of muscle pretensioning,
      postural changes, and intra-abdominal pressure (IAP). Four subjects participated
      in five to six experimental sessions in which a sudden load was applied by
      dropping a weight once a minute for 30 minutes. Electromyographic (EMG) data from
      10 trunk muscles, IAP data, and postural data were collected during the initial
      session and final sessions for each subject. The results indicate where each
      subject developed a unique preparatory strategy. The preparation always involved
      the pretensioning of the erector spinae muscles, although the coactivation of the
      other trunk muscles was quite variable across subjects. During the sudden loading
      the overall postural disturbance was not consistently reduced; however, the trunk
      flexion was significantly reduced in most subjects. Furthermore, the estimated
      spinal compression due to muscle loading was significantly reduced in all
      subjects.

PMID- 8272967
TI  - A carbon fiber implant to aid interbody lumbar fusion. Two-year clinical results
      in the first 26 patients.
AB  - The success of posterior lumbar interbody fusion (PLIF) has been limited by
      mechanical and biologic deficiencies of the donor bone. The authors have designed
      a carbon fiber-reinforced polymer implant that separates the mechanical and
      biologic functions of PLIF. The cagelike implant provides an actual device
      designed to meet the mechanical requirements of PLIF and replaces the donor bone
      with autologous bone, the best possible bone for healing. The authors report 2
      year follow-up results for their first 26 consecutive patients, 18 of whom were
      postsurgical failed backs with a total of 37 previous surgeries. At 2 years, 28
      of 28 PLIF cage fusion levels and 6 of 11 (54.5%) allograft levels exhibited
      radiographic fusion, a statistically significant difference at P = 0.0002.
      Clinical results were excellent in 11/26, good in 10/26, fair in 3/26, and poor
      in 2/26. Fair and poor results were attributable to objective identifiable
      problems unrelated to the carbon cage. The carbon implant achieved successful
      fusion in 6/6 (100%) of followed patients treated for a failed ETO allograft
      interbody fusion. A prospective controlled multi-centered study is being
      initiated.

PMID- 8272968
TI  - Intramedullary spinal cord sarcoidosis. Report of two cases.
AB  - Two cases of intramedullary spinal cord sarcoidosis are reported. These lesions
      could not be differentiated from neoplastic spinal cord tumors by clinical
      findings or imaging studies. In magnetic resonance imaging, the lesions were
      enhanced around the gray matter with gadlinium diethylene triamine pentaacetic
      acid (Gd-DTPA). The true diagnosis was established only by histologic examination
      of the surgical specimen. The possibility of intramedullary sarcoidosis
      presenting as a tumor should be included in the differential diagnosis of mass
      lesions of the spinal cord.

PMID- 8272969
TI  - The sickle ligament revisited. Release of the lumbosacral ligament via an
      anterior approach.

PMID- 8272970
TI  - Conus medullaris syndrome secondary to an L1 burst fracture in osteoporosis. A
      case report.

PMID- 8272971
TI  - Multiple cervical spine fractures without neurologic deficit after a helicopter
      crash. Case report.
AB  - The case of a soldier with multiple cervical fractures without neurologic deficit
      sustained after a helicopter crash during Operation Desert Storm is presented.
      The fractures involved the C2 body and the right facet joint and pedicle of C4.
      This fracture pattern, in association-with lack of neurologic deficit, is the
      first such case reported in the literature.

PMID- 8272972
TI  - Idiopathic spinal cord herniation. Report of two cases and review of the
      literature.
AB  - The authors experienced unique cases of spinal cord herniation. Only eight cases
      of spinal cord herniation have been reported formerly. The authors report two
      cases of spinal cord herniation accompanied with double structure of dura mater
      (duplicated dura mater). The causes of their condition are discussed in this
      report.

PMID- 8272973
TI  - Toxicological aspects of firesmoke: polymer pyrolysis and combustion.
AB  - Combustion toxicology is a complex field, and predicting the thermal breakdown
      products of natural and synthetic polymers is an inexact science. Practitioners
      of emergency medicine, occupational and environmental medicine, industrial
      hygiene, and toxicology must keep in mind a wide range of potential combustion
      and pyrolysis products when dealing with clinical and regulatory issues in fire
      safety.

PMID- 8272974
TI  - Clinical smoke inhalation injury: pulmonary effects.
AB  - Smoke-inhalation injury may range from lethal effects of entrapment in a burning
      closed structure to a minor exacerbation of preexisting asthma or bronchitis
      following a transient whiff of smoke. This article reviews the pathophysiology of
      smoke-inhalation injury and the clinical pattern of respiratory tract injury.
      Various diagnostic tools are used to determine the presence and severity of
      respiratory injury in order to guide management decisions. Despite improved
      understanding of the pathogenesis of smoke-inhalation injury, there is no proven,
      specific treatment which offers superior outcomes, and management focuses on the
      nonspecific effects of smoke inhalation on respiratory function, general support
      of the patient, and avoidance of iatrogenic problems.

PMID- 8272975
TI  - Clinical smoke inhalation injury: systemic effects.
AB  - Exposure to asphyxiant gases is a ubiquitous feature of the fire environment,
      particularly in structural (or closed-space) fires. The clinician evaluating the
      smoke-inhalation patient must keep in mind the manifold actions of systemic
      toxicants upon an individual whose pulmonary gas exchange may be compromised and
      whose circulatory and metabolic status may be stressed by burns, hypo- or
      hypervolemia, and intercurrent disease. Also to be considered is the likelihood
      of exposure to multiple toxicants whose physiologic effects may be synergistic
      and whose therapeutic demands may be conflicting. As newer therapeutic regimens
      and rapid laboratory tests become available, the clinician should be prepared to
      evaluate their strengths and limitations for the complex task of evaluating and
      treating smoke-inhalation patients.

PMID- 8272976
TI  - Metal fume fever.
AB  - Metal fume fever is an acute self-limited illness induced most commonly by
      inhalation of zinc oxide fumes. The affected individual characteristically
      experiences the rapid onset of intense shaking chills, fever, and body aches a
      few hours after exposure, and symptoms dissipate spontaneously. While the
      occurrence of metal fume fever appears to be widespread and the current TLV/PEL
      of 5 mg/m3 and STEL of 10 mg/m3 may not be fully protective, no chronic health
      sequelae have been documented to date. Nonetheless, as any worker who has
      experienced a full-blown case will likely testify, metal fume fever remains one
      of the more noxious short-term illnesses contracted in the workplace, and its
      prevention deserves serious attention.

PMID- 8272977
TI  - Polymer fume fever and other fluorocarbon pyrolysis-related syndromes.
AB  - Polymer fume fever usually occurs as a self-limited systemic illness with only
      minor pulmonary symptoms. Like metal fume fever, constitutional signs and
      symptoms typically present several hours after initial exposure, often giving
      rise to a misdiagnosis of viral "flu." Compared to metal fume fever, polymer fume
      fever has a more varied clinical presentation, the severity of which depends upon
      the specific conditions of exposure. When higher temperatures and/or longer
      durations of exposure are involved, significant pulmonary involvement, including
      radiographic consolidation, is a potential complication. Although a number of
      industrial outbreaks have implicated the smoking of contaminated cigarettes as a
      vehicle of exposure, any industrial or household activity in which PTFE is heated
      above 350-400 degrees C puts nearby workers or residents at risk of illness and
      is to be avoided without strict industrial hygiene controls.

PMID- 8272978
TI  - Toxic pyrolysis products of solvents, paints, and polymer films.
AB  - The organic chemicals used for solvents, paint, and polymer films are resistant
      to heat, but if the temperature is raised sufficiently, all will pyrolyze or
      degrade thermally to form new, lower-molecular-weight chemical species. The
      solvents include nonhalogenated and halogenated varieties, and their possible
      occupational exposures and reaction products are described. Paint and paint-like
      coatings, when pyrolyzed, always produce smoke, but toxic metals included as
      pigment may produce hazardous fumes. The condition "meat wrapper's asthma" is
      described to illustrate the effects once believed due to PVC pyrolysis.

PMID- 8272979
TI  - Environmental activation of pesticides.
AB  - Spray drift from application sites, runoff from agricultural fields, leftover
      products from home use, and accidental spills have made pesticide contamination
      ubiquitous in the environment. As a pesticide moves through the environment, it
      may react through chemical and biotic processes such as hydrolysis, oxidation, or
      reduction, or be metabolized in microorganisms, animals, plants, and humans. Most
      reactions will be inactivations, forming degradation products less toxic or
      persistent than the parent compound. However, some reactions are activations,
      creating breakdown products equally or more toxic, persistent, or mobile than the
      parent and posing a greater threat to nontarget organisms and the environment.
      Examples are drawn from the major classes of pesticides including organochlorine
      compounds (DDT and aldrin), organophosphorus pesticides (malathion), carbamate
      pesticides (aldicarb), and fungicides to illustrate the various activation
      routes.

PMID- 8272980
TI  - Environmental transformation of toxic metals.
AB  - Because toxicity varies enormously with the chemical state of metals,
      transformations in the environment control the level of the human health hazard.
      Important transformation processes include adsorption and desorption from soils
      and sediments, oxidation and reduction (redox) reactions, biotic metabolism,
      formation of organic metal compounds, and bioaccumulation. The six metals
      detailed in this chapter--arsenic, cadmium, chromium, lead, mercury, and selenium
      -were chosen because of their toxicity, frequency of occurrence at hazardous
      waste sites, and involvement in environmental contamination.

PMID- 8272981
TI  - Hazardous combustion products from municipal waste incineration.
AB  - Metropolitan areas are experiencing waste management problems due to the
      considerable volume of municipal waste generated and the limited space for
      landfills. Some communities are including incineration as part of their waste
      management strategy. Incineration is the destruction of materials by the
      controlled application of heat and is a chemically complex process that leads to
      the de novo formation of a large number of compounds, many of which have known
      toxicologic properties. This article explores some of the de novo toxicants
      formed during incineration of municipal waste and hazardous waste.

PMID- 8272983
TI  - A personal perspective on growing old.

PMID- 8272982
TI  - Atmospheric formation and fates of toxic ambient air pollutants.
AB  - Concentrations of de novo toxicants in ambient air are typically in the ppb
      range, compared to ppm for occupational exposures. Despite this, some species
      such as ozone, alone or in combination with other pollutants, have significant
      health impacts, especially on populations such as children, the elderly, and
      asthmatics. Reaction products in the atmosphere include gases such as ozone and
      nitric acid, as well as polar organic species such as aldehydes, acids,
      hydroperoxides, and peroxides. A brief discussion of indoor vs outdoor levels of
      several acids/toxicants is included. Emphasis is on homogeneous, gas-phase
      processes with some examples of gas/solid heterogeneous processes. A brief
      discussion is included on the role of chlorofluorocarbons in the catalytic
      destruction of stratospheric ozone in the context of the resulting expected
      increase in ultraviolet radiation at the earth's surface.

PMID- 8272985
TI  - A prospective survey of hospital ambulatory dental emergencies. Part 1: Patient
      and emergency characteristics.
AB  - Part 1 of this study describes the dental disorders and patient characteristics
      of 253 patients who presented as dental emergencies to the University Hospital
      dental clinic, Vancouver, BC, during a three-month period. Most patients had a
      true perception of what constitutes a dental emergency. Dental pain was the
      predominant reason for seeking help, and the pain existed for more than seven
      days prior to contact in more than 50% of patients. Patients were not always able
      to identify the number and location of painful teeth, and a perceived low cost
      for treatment was a major reason for contacting the hospital. Reliability of
      emergency patients in keeping scheduled appointments was very high. Almost 69% of
      patients did not see a dentist regularly. Referrals to the hospital dental
      service were most numerous in the summer months. Diagnosis of the complaints
      revealed infection to be the cause of pain in 76.7% of patients.

PMID- 8272984
TI  - Comparisons between dentist ratings and self-ratings of dental appearance in an
      elderly population.
AB  - Little is known about dental appearance in terms of the elderly population. The
      purpose of this paper is to compare self-reported dental appearance with dentist
      rated appearance for individuals over 65. The subjects (N = 550) were
      participants in the Los Angeles based Medicare Screening and Health Promotion
      Trial. Most were female (57.3%), white (89.0%), and married (62.0%), with a mean
      age of 74.5 years. About one-third had incomes greater than $25,000. Results are
      based on a 45 minute telephone interview and onsite dental screening. Findings
      show that 40% of the self-ratings on a five point scale were higher than the
      dentist ratings, and 22% were lower. Bivariate analyses showed that both sets of
      ratings were related to dental status variables, self-reported health, and
      education. High self-ratings were also associated with being white and having a
      positive mental health status, while high dentist ratings were associated with
      patients who were younger, married, and who had higher income and social network
      scores. Comparison of results from two multiple regressions showed unique
      predictors for the self-ratings (marital status and GOHAI scores) and for the
      dentist ratings (sex and income). These discrepancies can raise barriers to
      effective treatment planning in the elderly, which could affect utilization and
      satisfaction.

PMID- 8272986
TI  - The dental status of dentate institutionalized older adults: consideration of
      retained roots.
AB  - Many studies have described the general dental findings in institutionalized
      older patients, but few studies have used standard dental indices to describe the
      dental status of these populations. Eighty-five dentate nursing home residents
      were examined by a single dentist. Dental findings were reported by means of the
      DMFS, DMFT, and RCI indices along with the D/DFS ratio for coronal and root
      caries. The mean DMFS, DMFT, and RCI were 97.0, 22.9, and 28.7%, respectively.
      The percentages of untreated coronal and root caries lesions, as measured by the
      D/DFS ratios were 65.4% and 85.4%, respectively. Forty-eight percent of the
      subjects had at least one retained root, with a mean of 1.0 for all 85 subjects.
      None of the dental findings was statistically significant in association with
      age, gender, or length of stay in the institution. In the population examined, no
      statistical or clinical differences in relation to age, gender, or length of stay
      in the institution were found. The dental status of a dentate older adult
      population can be accurately described by means of the standardized indices of
      DMFS, DMFT, and RCI along with the D/DFS ratios, with the caveat that these
      indices must be interpreted differently than when used with pediatric
      populations. Retained roots present a fifth surface at risk for root caries, the
      occlusal surface. The role of the occlusal root surface in the dental status of a
      population needs to be reported and analyzed.

PMID- 8272987
TI  - Dental management of a child with Huntington's disease: case report.
AB  - Huntington's Disease is a chronic, progressive, hereditary disorder of unknown
      etiology. Onset occurs between 35 and 42 years of age and is characterized by
      chorea, behavioral changes, dementia, and irregular gait. Dyslalia is a common
      feature due to the severe darting movements of the tongue and head. Huntington's
      Disease is rarely diagnosed in children (less than 1% of all cases are documented
      in children under 10 years of age). This is a case report of an 11 year 5 month
      old white male, diagnosed at age 5, who was brought to the University of
      Minnesota Hospital Dental Clinic for an oral examination. The findings are
      presented, and the management of patients with Huntington's Disease is discussed.

PMID- 8272988
TI  - A review of liver transplantation for the dentist and guidelines for dental
      management.
AB  - The number of recipients of liver transplants has grown rapidly in the last few
      years and is likely to continue to do so in the future. The dentist should be
      prepared to see individuals who are contemplating or have had liver transplants.
      The major goal of dental intervention, before and after liver transplantation, is
      the prevention of bacteremia from an oral source that could lead to systemic
      infection. In addition, pre-transplant medical conditions of concern to the
      dentist include poor drug metabolism, bleeding disorders, poor wound healing, and
      an inability to metabolize swallowed blood. Post-transplant dental treatment must
      take into consideration immunosuppressive drugs and the potential for infections.
      Dental treatment should include a thorough dental examination, elimination of
      dental problems that could cause medical problems, and an intensive preventive
      dentistry program to minimize the occurrence of dental disease.

PMID- 8272989
TI  - Use of the SADP for measurement of attitudes of Chinese dental students and
      dental surgery assistants toward disabled persons.
AB  - The purpose of this study was to determine the attitudes of Chinese dental
      students and dental surgery assistants toward disabled persons using the Scale to
      Determine Attitudes Toward Disabled Persons, the SADP. A group of 99 Hong Kong
      University psychology students, 50 male and 49 female, was used as the control
      and to determine the internal consistency and reliability of the Chinese version
      of the scale. A group of 4th year (n = 25) and a group of 3rd year (n = 46)
      dental students and a group of in-house dental surgery assistants (n = 86) at the
      Prince Philip Dental Hospital, Hong Kong, were asked to complete a Chinese
      translation of the SADP. Results showed that there was no significant difference
      between attitude scores of 3rd and 4th year dental students (p = 0.06). There was
      a significant difference in attitude scores between dental students and the
      dental surgery assistants (p < 0.001), with those of dental students being lower.
      In the control group, there was no significant difference between female control
      and dental surgery assistant scores (p = 0.289). There was a significant
      difference between dental students and male control scores (p < 10(-6)). Not only
      did the dental students score lower than the dental surgery assistants, but they
      also scored significantly lower than a group of non-dental students of the same
      University.

PMID- 8272991
TI  - Surgical endoscopy--a worldwide phenomenon.

PMID- 8272990
TI  - Portal hypertension management.
AB  - Injection sclerotherapy is the mainstay of treatment for acute variceal bleeding
      and for long-term management after a variceal bleed. In those few patients in
      whom sclerotherapy fails to control acute bleeding, either a surgical shunt or a
      simple esophageal transection is recommended. A surgical shunt or a more
      extensive esophagogastric devascularization and transection operation is
      advocated for the failures of long-term sclerotherapy management. The role of
      pharmacological agents in acute variceal bleed management remains in question,
      and the use of propranolol in long-term management, either as an alternative to
      sclerotherapy or in combination with sclerotherapy, is controversial. The
      definitive roles of the newly described variceal banding and transjugular
      intrahepatic porto-systemic shunts (TIPS) procedures have yet to be established.
      All patients presenting with end-stage liver disease and esophageal variceal
      bleeding should be evaluated for a liver transplant, although few will qualify. A
      possible future transplant should be kept in mind when emergency treatment is
      planned. Any form of prophylactic therapy for patients with esophageal varices
      that have not yet bled will remain unjustified until those patients at high risk
      of a first variceal bleed can be identified. The gastric mucosal lesion, portal
      hypertensive gastropathy, has been underdiagnosed in the past. Although bleeding
      does occur, it is seldom a major clinical problem. When necessary, bleeding can
      be controlled by propranolol or a surgical shunt.

PMID- 8272992
TI  - Preincisional local anesthesia with bupivacaine and pain after laparoscopic
      cholecystectomy. A double-blind randomized clinical trial.
AB  - The aim of this study was to investigate whether local anesthesia of abdominal
      wall wounds prior to laparoscopic cholecystectomy leads to decreased pain beyond
      the immediate postoperative period and thus improves the comfort of the patient.
      In a randomized, double-blind study 50 patients scheduled for laparoscopic
      cholecystectomy were divided into two groups. In one group (n = 25) the skin,
      subcutis, fascia, muscle, and preperitoneal space were infiltrated with 8 ml of
      bupivacaine 0.5% 5 min before each abdominal wall incision. The control group (n
      = 25) received normal saline. The intensity of pain was assessed by a 100-point
      visual analogue scale (VAS) at rest and during movement and by the consumption of
      analgesics. Analgesic therapy was provided by on-demand analgesia with
      piritramide intravenously for 24 h and continued by ibuprofen orally on request.
      The mean intensity of pain at rest and during movement was lower but not
      statistically significant in patients who received bupivacaine compared to the
      control group up to the second postoperative day. The difference was between 4
      and 9 VAS points and therefore of doubtful clinical relevance. Similar
      statistically nonsignificant results were found for the mean consumption of
      piritramide up to 16 h after the operation. Three patients (12%) in the
      bupivacaine group localized the most severe pain up to the second postoperative
      day to the right lower abdominal wall wound where the gallbladder had been
      extracted compared to 11 patients (44%) of the control group (P = 0.012). These
      results indicate that bupivacaine was effective at the site where it was
      administered.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272993
TI  - Laparoscopic cholecystectomy produces less postoperative restriction of pulmonary
      function than open cholecystectomy.
AB  - This study was undertaken to determine whether laparoscopy produces less
      postoperative decrease in pulmonary function than does open operation. Ten
      elective laparoscopic cholecystectomy patients (LC group) were compared to 10
      elective open cholecystectomy patients (OC group). Spirometry was performed
      preoperatively and then postoperatively as soon as each patient was awake and
      cooperative. The two groups were similar with respect to age, gender, and
      preexisting medical illness. No patient had underlying cardiopulmonary disease.
      Postoperatively, forced vital capacity, forced expiratory volume in 1 s, and
      maximum forced expiratory flow decreased to 56%, 55%, and 43% of preoperative
      values in the OC group and to 72%, 76%, and 81% of preoperative values in the LC
      group. These decreases were significantly greater in the OC group as compared to
      the LC group, P values < or = 0.05. Cholecystectomy had a significant restrictive
      effect on immediate postoperative pulmonary function. Laparoscopic
      cholecystectomy produced significantly less restriction.

PMID- 8272994
TI  - Hemodynamic events in the peritoneal environment during pneumoperitoneum in dogs.
AB  - The purpose of this experimental study was to determine the hemodynamic
      conditions of intraperitoneal viscera during pneumoperitoneum by using either CO2
      gas or helium (He) for insufflation. In 16 mongrel dogs (divided into a CO2 group
      and an He group) subjected to 14 mmHg pneumoperitoneum for 60 min, the following
      parameters were assessed at times before and 1, 2, 5, 15, 30, 45, and 60 min
      thereafter: (1) intestinal mucosal blood flow, by means of a laser-Doppler probe
      inplanted into a jejunal loop; (2) portal pressure and portal blood pCO2, through
      a catheter inserted via a mesenteric jejunal vein; (3) intramural jejunal pH
      (pHi), by means of a Tonometer, which expresses the degree of tissue ischemia;
      (4) inferior vena cava pressure and blood pCO2, through a catheter inserted via a
      femoral vein; and (5) from the systemic circulation pulse rate, arterial blood
      pressure, CO, CVP, PVP, SaO2, pCO2, and paO2 were measured through a catheter
      placed into a femoral artery and a Swan-Ganz thermodilution catheter inserted via
      external jugular vein: CI and SVR were then calculated. Jejunal mucosal blood
      flow was found decreased (P < 0.0001) and pHi revealed gut mucosal ischemia.
      Portal and inferior vena cava pressures were found to be elevated (P < 0.0001),
      as was blood pCO2 of these vessels (P < 0.001), in only the CO2 group. From the
      systemic circulation, arterial blood pressure, CO, CI, SaO2, and paO2 revealed a
      decrease (P < 0.001) while arterial pCO2 (only CO2 group), CVP, SVR, and PVP
      revealed an increase (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8272995
TI  - Alterations in respiratory function and hemodynamics during laparoscopic
      cholecystectomy under pneumoperitoneum.
AB  - Respiratory function and hemodynamics were studied during laparoscopic
      cholecystectomy (LC) under a 10 mmHg pneumoperitoneum (PP) by carbon dioxide
      insufflation. Blood-gas analysis and measurement of cardiac function by using a
      Swan-Ganz catheter were performed. Creatinine clearance rate was measured
      preoperatively and intraoperatively. Compared with values obtained before the
      institution of PP, blood-gas analysis showed a significant increase in PCO2 (P <
      0.01), and a significant decrease in pH (P < 0.01) and base excess (P < 0.05)
      during PP. With respect to cardiac function, there was no significant change in
      cardiac output, pulmonary arterial pressure, and pulmonary arterial wedge
      pressure. Intraoperative creatinine clearance rate (Ccr) was decreased in 29 of
      48 cases, increased in 18 cases, and unchanged in 1 case, resulting in no
      significant difference overall between the values measured preoperatively and
      intraoperatively. However, in eight individual cases, the Ccr was found to have
      decreased significantly. Although alterations in respiratory function were
      observed, LC at 10 mmHg PP did not cause any crucial problems in respiratory or
      cardiac function. It should be kept in mind, however, that renal blood flow may
      decrease in some cases even at intraabdominal pressures under 10 mmHg.

PMID- 8272996
TI  - Multicenter prospective evaluation of laparoscopic antireflux surgery.
      Preliminary report.
AB  - BACKGROUND: A prospective study of 116 patients undergoing laparoscopic
      antireflux surgery was undertaken in four centers in the United Kingdom and the
      United States. METHODS: Patients with a hiatal hernia (n = 80) underwent total
      Rosetti-Hell fundoplication, whereas those without a hiatal defect (n = 36) were
      treated by a partial fundoplication (Toupet). The follow-up period ranged from 3
      to 24 months; median was 13 months. RESULTS: The median duration of the
      operations was 2.5 h. Intraoperative complications were encountered in 16
      patients (14.0%) and conversion to laparotomy was necessary for esophageal
      perforation in one. The postoperative recovery of gastrointestinal function was
      rapid and the median hospital stay from the time of the operation to discharge
      was 2 days, range 1-10. A good symptomatic result (> 70% reduction of
      preoperative symptom score) was observed in 106 patients (91%). There were no
      postoperative deaths but 15 patients (13.0%) developed complications in the
      immediate postoperative period. At 3 months, complete endoscopic healing of the
      esophagitis was observed in 65/92 patients (71%) and improvement by at least one
      grade was seen in 19 patients (21%). Twenty-four-hour pH monitoring, which was
      abnormal preoperatively in 93% of patients, was normal after surgery in 95%.
      There were 10 symptomatic failures (persistent reflux symptoms) and 14 patients
      (12%) developed adverse symptoms related to the procedure (gas-bloat 8, dysphagia
      9, gastroparesis 1, explosive diarrhoea 1). Readmission to hospital within 3
      months was necessary in 9 patients. CONCLUSIONS: Laparoscopic antireflux surgery
      can be performed with a low morbidity. In the short term, 83% of patients were
      rendered symptom free. These results are similar to those reported after the
      equivalent open operations.

PMID- 8272997
TI  - Experimental videothoracoscopic cannulation of the left atrial appendix. A
      feasible rapid approach for initiating left heart bypass?
AB  - Rapid implementation of left ventricular assistance without thoracotomy for
      temporary support of patients with severe, life-threatening, acute cardiac power
      failure potentially expands applications of such support devices. A thoracoscopic
      technique for direct cannulation of the left atrium is described. In healthy
      closed-chest pigs, it proved a feasible method for effective volume unloading of
      the left ventricle.

PMID- 8272998
TI  - Laparoscopic transcystic duct balloon dilatation of the sphincter of Oddi.
AB  - Balloon dilatation of the sphincter of Oddi has been performed via a laparoscopic
      transcystic duct technique. Small common duct stones and stone debris have been
      successfully lavaged into the duodenum in 17 of 20 cases (85%) by this method.
      Postoperative hyperamylasemia was noted in four patients. Mild clinical
      pancreatitis was observed in three patients (15%). Further evaluation of this
      technique as an adjunct to laparoscopic common bile duct stone extraction is
      warranted.

PMID- 8272999
TI  - Long-term clinical and endoscopic assessment after total gastrectomy for cancer.
AB  - Progressive malnutrition has been reported as a long-term consequence of total
      gastrectomy (TG), possibly related to the mode of reconstructing the intestine.
      In reviewing our personal experience (1975-Sept. 91), we attempted to correlate
      the reconstructive technique used with the subsequent course of the patient. A
      consecutive series of 62 TGs (59 adenocarcinomas, 3 lymphomas) in 38 males and 24
      females 59 +/- 11 (m Mean +/- SD) years old was reviewed. Preoperative and
      "follow-up" evaluations, including upper gastrointestinal series and/or
      endoscopic examination, complete blood count, serum and liver biochemistry
      profiles, serum iron and plasma transferrin, oral GTT, USG or CT scan, actual and
      ideal body weight (IBW Life Extension Institute of New York), and "performance
      status" assessments, were prospectively documented. The follow-up symptoms were
      classified as per Cuschieri's scoring system. The endoscopic esophageal mucosa
      assessments were documented as well. Among 56 patients surviving operation, 34
      were available, without tumor recurrence, for long-term (12-132 months)
      evaluation. A Roux-en-Y loop reconstruction had been performed in 23, 5 with a
      Hunt-Lawrence pouch; an isoperistaltic, esophagoduodenal, jejunal interposition
      (IR) was performed in 9, 4 with a Kock pouch; and an omega loop reconstruction
      was performed in 2. A 60-70-cm-long jejunal limb was always utilized.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8273000
TI  - Endoscopic ultrasonography verifies effect on endoscopic treatment of reflux in
      dogs and man.
AB  - We have previously reported that endoscopic sclerosis of the gastric cardia is an
      effective treatment for experimental gastroesophageal reflux in dogs. The
      histologic effect of endoscopic sclerosis is limited to the proximal stomach;
      mucosal deformity provides endoscopic evidence of sclerosis, and the intramural
      effects are shown by ultrasonographic technique. This report describes histologic
      and ultrasonographic results in the dogs at the completion of endoscopic
      sclerosis. This report also describes the endoscopic ultrasound results in the
      first two patients who have completed endoscopic treatment for reflux by means of
      endoscopic sclerosis of the gastric cardia. All canine and human subjects had
      sonodense lesions involving all layers of the proximal stomach at the injection
      site at the conclusion of treatment. Histologic examination of canine tissues
      showed dense submucosal and muscularis fibrosis in the stomach; the esophagus was
      normal. Endoscopic ultrasound demonstrates the effect of endoscopic sclerosis;
      this technique may be useful in the evaluation of symptomatic responses after
      this treatment.

PMID- 8273001
TI  - Nonoperative management of esophageal perforation secondary to balloon
      dilatation.
AB  - Esophageal perforation is usually considered a surgical emergency. However,
      esophageal perforation after therapeutic endoscopic manipulation is a different
      entity. This type of perforation occurs in a controlled environment and the
      perforation is usually detected early. Three documented cases of perforation
      during endoscopic balloon dilatation are described. They were successfully
      treated nonoperatively.

PMID- 8273002
TI  - Rotation of the terminal ileum in laparoscopic right hemicolectomy.
AB  - This case report describes rotation of the terminal ileum in a patient who had a
      laparoscopic right hemicolectomy. To prevent this complication, the terminal
      ileum should be inspected laparoscopically for rotation before exteriorization of
      the terminal ileum and, in addition, after completion of the anastomosis.

PMID- 8273003
TI  - Entrapment of small bowel after laparoscopic herniorrhaphy.
AB  - As laparoscopic hernia repair continues to evolve as an operative procedure,
      papers will continue to be published discussing new variations and new techniques
      which will better the operative procedure as a whole and quite possibly decrease
      its associated complications (i.e., morbidity and mortality). We present a case
      of laparoscopic bilateral herniorrhaphy in which after uncomplicated surgery and
      an immediate, uneventful postoperative course, the patient returned to our
      institution with both a rectus sheath hematoma and small bowel obstruction. The
      patient, who was initially treated conservatively, ultimately required laparotomy
      for persistent small bowel obstruction. Laparotomy revealed incarcerated small
      bowel in a cavity between the posterior rectus fascia and the rectus muscle
      proper. The patient did well after laparotomy and was discharged home with no
      further complications.

PMID- 8273004
TI  - Laparoscopic cholecystectomy. Leave no (spilled) stone unturned.
AB  - Stones are sometimes spilled at the time of cholecystectomy. Retrieval may be
      difficult, especially during laparoscopic cholecystectomy. Little is known about
      the natural history of missed stones which are left behind in the peritoneal
      cavity. We present a case in which a patient developed an intraabdominal abscess
      around such a stone. The abscess recurred after drainage and removal of the stone
      was needed for resolution. This case suggests that care should be taken to avoid
      stone spillage, and that stones which are spilled into the abdomen should be
      retrieved.

PMID- 8273005
TI  - Lap simulator, animal studies, and the Laptent. Bridging the gap between open and
      laparoscopic surgery.
AB  - In an effort to ensure proper training and to establish a routine amongst the
      surgical team right from the start, we began practicing laparoscopic techniques
      with the lap simulator. After having acquainted ourselves with the fundamentals
      of this minimal-invasive method, we applied our newfound experience to the animal
      model. Even though the subsequent studies with pigs were the best learning model
      in which to practice different surgical techniques--e.g., ureter clipping and
      renal vessel triple stapling with the Endo-GIA--various problems can arise in a
      true clinical situation since anatomical diversity exists between an animal and
      human situs. We found that a compromise could be reached by simulating
      laparoscopic conditions during open surgery without endangering the safety of the
      patient during any point of the operation. After open surgical exposure of the
      Gerota fascia was carried out, the operative site was completely covered with the
      Laptent. From this moment on, all operative steps were performed with
      laparoscopic instruments under continuous video monitoring. Our step-by-step
      training program has exposed the surgeon and OR staff to the complexity of this
      new surgical technique. The use of the Laptent has successfully bridged the gap
      between open and laparoscopic surgery. Most important of all, those surgical
      centers without access to extensive experimental studies will realize that
      Laptent-assisted surgery can be of benefit and facilitate the clinical
      introduction of this minimal-invasive method.

PMID- 8273006
TI  - Technique of ultrasound examination during laparoscopic cholecystectomy.
AB  - Intracorporeal ultrasonography was used as a new method to examine the bile ducts
      during laparoscopic cholecystectomy. A prototype rigid 7.5-MHz ultrasound probe,
      10 mm in diameter and 50 cm in length, was introduced during 25 laparoscopic
      cholecystectomies. A dual scanning technique was developed for complete
      examination of the bile duct. This entailed transverse scanning via the
      subxyphoid trocar and longitudinal scanning via the umbilical trocar. The
      intrahepatic ducts were also visualized by placing the probe on the liver
      surface. Color Doppler imaging was useful to quickly distinguish the duct from
      vascular structures. Laparoscopic ultrasonography clearly delineated the bile
      ducts in all operations except one. The time required for imaging was
      significantly shorter for ultrasonography than for cholangiography. Our
      preliminary experience demonstrates that a complete examination of the bile ducts
      can be performed with intracorporeal ultrasonography in a relatively short period
      of time.

PMID- 8273007
TI  - Laparoscopic herniorrhaphy. A preperitoneal tension-free approach.
AB  - At the present time laparoscopic herniorrhaphy appears to be successfully
      performed by utilizing a preperitoneal approach. The major indications are
      bilaterals hernia and the recurrent hernia. Other routine hernias may be done at
      the decision of the surgeon and patient depending upon the necessity of rapid
      return to work and desire to minimize pain. Utilizing this approach, the
      recurrence rate at the present time is less than 1%, which compares favorably
      with all other types of repair.

PMID- 8273008
TI  - 3-D imaging in gastrointestinal laparoscopy.

PMID- 8273009
TI  - The vertical infraumbilical incision for laparoscopic surgery.

PMID- 8273010
TI  - More on ERCP and laparoscopic cholecystectomy.

PMID- 8273011
TI  - [Magnetic resonance morphologic changes in shoulder joints of world class water
      polo players].
AB  - In a prospective study we examined the dominant shoulder of 11 athletes from the
      1992 German Olympic water polo team. Their mean age was 25.4 +/- 3.5 years. Water
      polo had been practised generally for 14.1 +/- 4.3 years and professionally for
      11.6 +/- 3.9 years. The weekly training amounted to between 12.5 and 19.5 hours.
      All athletes were submitted to standardised clinical, sonographical and MRI
      tests. In 5 cases we found anamnestic and/or clinical indications of rotator cuff
      pathology. In all 5 cases the supraspinatus tendon was affected, and in three
      cases both the supra- and the infraspinatus tendon were involved.
      Sonographically, no specific pathology except a thickened rotator cuff was seen.
      Remarkable changes were revealed by magnetic resonance imaging. In 8 cases
      changes were present in the insertion of the rotator cuff at the humeral head.
      The subacromial bursa was not pathologic. The tendon of the long head of the
      biceps was pathologically changed in 9 cases. In 7 athletes a so-called biceps
      halo and in two an osteophyte in the area of the bicipital groove was visible. In
      all of the 11 dominant shoulder joints massive hypertrophy of the articular
      capsule and pathologic changes of the anterior glenoid labrum existed. Occult
      osseous lesions were detected in 5 athletes, and osseous lesions of the humeral
      head in 8 athletes. In all athletes we could document degenerative changes at the
      acromioclavicular joints such as effusion in 7 cases, arthritis in two cases, and
      evident synovitis in two cases. CLINICAL RELEVANCE: Many of the changes detected
      by MRI were not symptomatic.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273012
TI  - [Instability and impingement of the shoulder of the high performance athlete in
      overhead stress].
AB  - The present prospective study was performed on 89 competitive sportsmen (league
      players of handball, basketball, volleyball and water polo). The evaluation was
      based on information obtained from a review of training methods, a standardised
      anamnestic, physical and sonographic examination directed at pain, function,
      flexibility and all signs of impingement and instability of the shoulder counted
      in a score. The incidence of shoulder pain, which handicapped during training and
      play within the last 6 months was for water polo 60%, handball 40%, volleyball
      25% and basketball 3.5%. Analysing these problems we found severe problems
      predominantly in handball, fewer in water polo or volleyball. According to data
      obtained from sports with throwing activity we found a high incidence of shoulder
      disorders. Using basketball players as a control group with less throwing
      activity our results would suggest that this mechanism seems to be the most
      important. The high incidence of severe disorders in handball players is
      additionally caused by traumatic injuries. Ultrasonography shows predominantly
      incomplete tears of the deep surface of the supraspinatus tendon near to the
      insertion with exception of the basketball players. Only in 5 shoulders (2.8%) we
      found the coincidence of clear signs of instability and subacromial pathology.
      The term "instability impingement" has not proved to be very helpful and has
      turned out to be far too diffuse to establish a diagnosis.

PMID- 8273013
TI  - [EMG-assisted functional analysis within the scope of follow-up of
      arthroscopically managed injuries of the anterior cruciate ligament].
AB  - The rehabilitative course of anterior cruciate ligament ruptures was followed up
      at 16.6 months postoperatively be measuring clinical parameters, isokinetic power
      values and by means of electromyographic leads. The injured side has
      significantly looser ligaments than the non-injured one (p = < 0.01). The
      circumferential measures differ from each other, pointing to a reduction in
      muscular circumference at the measuring points 10 cm and 20 cm above the medial
      joint cavity (p = < 0.05). The isokinetic measurements had selective deficits of
      the knee-joint extensor at 60 degrees W/S (p = < 0.01) and at 180 degrees W/S (p
      = < 0.05), whereas the flexors did not show any difference, irrespective of the
      side. EMG measurements after 16.6 months via superficial leads applied to the
      synergistic compound of the extensors of the knee joint did not confirm any
      weakness of the m. vastus medialis although such weakness has often been claimed
      to exist. Laterally changed electromechanical coupling was seen, as well as a
      changed muscular fatigue pattern. The changed synergistic functional capacity of
      the m. quadriceps femoris could be of pathogenetic importance for further, e.g.
      retropatellar, subsequent damage. The author discusses the question whether
      laterally equal muscular conditions based on traumatically changed conditions in
      the joints should be treated at all.

PMID- 8273014
TI  - [Surgical treatment of soccer player's ankle joint].
AB  - In experienced football players spurring and calcifications of the ankle joint's
      capsule attachments may be found more often than in other sportsmen. Basing on
      functional and sometimes already established ankle joint instability pain may
      develop. Out of 374 football players throughout 1989-1992 with injuries to the
      ankle joint 49 were operated on. These showed chronical instability and
      radiologically visible alterations in accordance with the imaging of footballer's
      ankle joint. 40 of these patients could be followed up. 16 exact fibular ligament
      repairs and 19 reconstructions were performed, 15 tibioventral, 6 talodorsal, 12
      fibular and three medial capsule calcifications and spurs were excised, 8 loose
      bodies removed, three cases of osteochondritis dissecans drilled. After an
      average follow up of 25.6 months we saw stable ankle joints in all patients with
      resting local pain in 15 patients, among them 7 load dependent and 6 with slight
      limitation of dorsiflexion. Sport activity level showed 25 patients improved, 11
      equal, one worse and three with changed disciplines.

PMID- 8273015
TI  - [Compression neuropathy of the suprascapular nerve in high performance volleyball
      players].
AB  - Individual observations during the course of the medical care of the German men's
      national volleyball team in international tournaments gave cause to investigate
      more thoroughly the increasing occurrence of an atrophy of the infraspinatus m.
      in volleyball players at international level. An examination of three men's
      national teams specially slanted to throw light on this problem revealed that 28%
      (10 out of 36 players) had an atrophy of the infraspinatus m. On the basis of
      these findings, a prospective study was carried out, with the object of
      clarifying to what extent a developing or manifest compression neuropathy of the
      suprascapularis n. was present in a defined population of high-level volleyball
      players (1st National League, men). 32 players were examined as to the extent to
      which a functional impairment of the suprascapularis n. occurred in the pursuit
      of the competitive sport of volleyball. The study revealed a functional
      impairment of the suprascapular n. in 45% of the both clinically and
      neurophysiologically examined sportsmen. It follows in consequence that a control
      examination is advisable in the case of a latent disorder, so as to detect any
      continuation or possible deterioration. In the event of a developing or manifest
      atrophy of the infraspinatus m. the operative relief of the suprascapular n. in
      the region of the scapular incisure may be considered in addition to conservative
      therapy.

PMID- 8273016
TI  - [Creative medicine--from risk to innovations].

PMID- 8273017
TI  - Fort Worth District Dental Society mass disaster dental team's Mt. Carmel fire
      experience: clinical overview.

PMID- 8273019
TI  - Change impacts dental program.

PMID- 8273018
TI  - New drugs from 1991-1992.

PMID- 8273020
TI  - [From Aristotle to the cochlear implant. A contribution to the history of hearing
      disorders].

PMID- 8273021
TI  - [Hearing disorders in childhood].
AB  - Hearing impairment in children may severely affect language acquisition.
      Therefore, early identification and expedient auditory rehabilitation is
      important. Hearing impairment should be diagnosed within the first year of life.
      Unfortunately, hearing handicap is still recognized at an average age of two
      years. In 70% of the cases, the hearing impairment is first suspected by the
      parents. The hearing of children at risk should be assessed using systematic
      screening programs. Parents who suspect that their child is hearing impaired must
      be taken seriously, and a thorough pedaudiologic evaluation is necessary. The
      principles of auditory rehabilitation are outlined.

PMID- 8273022
TI  - [Presbycusis].
AB  - Hearing loss in the elderly is the most common type of hearing impairment. The
      term presbyacusis has been used to describe this category of hearing loss when
      there are no other etiological factors. However, the term is not precise, because
      any of several locations along the auditory pathway may be involved to produce
      the symptoms. The diagnosis is based more on the course of the hearing loss and
      the associated biological signs of aging than on specific criteria. The loss of
      speech-understanding ability is one of the most important indicators for a
      therapeutic intervention, which generally aims at amplification using a personal
      hearing aid. An improvement in speech-understanding ability with a hearing aid
      depends on several complex factors, and there is a large amount of intersubject
      variability in the benefit derived from amplification, even when the magnitude of
      the hearing loss is comparable. The aim of research on presbyacusis over the next
      several years--keeping in mind the demographic development in the industrialized
      countries--will be to further the differential analysis of the factors
      contributing to auditory communication disorders in the aging population.

PMID- 8273023
TI  - [Retrocochlear hearing disorders].
AB  - Sensorineural hearing loss is a common disorder that results from damage to the
      inner ear in over 95% of all cases; therefore, retrocochlear hearing disorders
      are rare and cannot be differentiated from sensory losses by clinical symptoms
      alone. Associated vestibular and other neurotological symptoms must lead to
      appropriate diagnostic procedures. Besides audiological and neurotological tests,
      e.g. auditory-evoked potentials, otoacoustic emissions or electronystagmography,
      modern imaging methods are the most valuable tools to detect tumorous, vascular
      and inflammatory processes. Acoustic neuromas, which are the most frequent
      causes, require otoneurosurgery with the attempt to preserve hearing and facial
      nerve function. Multiple sclerosis and vascular lesions of the vertebral arteries
      or their branches require an interdisciplinary approach. Due to recent advances
      in diagnostics, imaging and management, retrocochlear disorders have gained much
      interest from otologists in the last few years. They provide new insight into the
      physiology and pathophysiology of hearing.

PMID- 8273024
TI  - [Sudden deafness].
AB  - Sensorineural hearing loss with rapid onset occurring without obvious reasons is
      considered a clinical entity called sudden hearing loss. Such hearing
      dysfunctions must be rated as severe handicaps, comparable to a sudden loss of
      vision. Neither the patient nor the physician should regard sudden deafness as a
      minor incident. An immediate and meticulous search for possible causes is
      mandatory. As a first step, an otoscopic examination should be carried out, and
      the hearing loss must be documented by an audiometric evaluation. Further steps
      of management will be tailored according to the results of these examinations. In
      some cases, immediate therapeutic measures must be taken to improve the patient's
      hearing loss. Therefore, an emergency referral of the patient to an otologist is
      to be recommended in all cases of sudden hearing loss.

PMID- 8273025
TI  - [Extensive hearing loss and deafness in adults].
AB  - Hearing and understanding are two related, yet different processes. Hearing is
      the perception of sound. It can be of enormous value to patients with severely
      impaired hearing, as it facilitates acoustic orientation. An understanding of
      speech, however, remains virtually impossible for most of these patients.
      Nevertheless, early habituation to their acoustic situation makes lip-reading
      much easier, thus enabling conversations to be possible in good listening
      environments. Severely impaired patients, however, are still not in a position to
      follow conversation in larger groups. Even with hearing aids and the deployment
      of the latest technology, sufficient help is not always given. Before making a
      decision on the use of these technical aids, the ENT specialist should discuss
      the needs of the particular individual with the hearing-aid specialist. Provided
      that residual hearing can be used to understand speech with the help of a hearing
      aid, intracochlear implantation of an electronic prosthesis is not indicated. A
      cochlear implant is indicated when there is a complete hearing loss on both
      sides. Such a profound loss means that sufficient understanding of speech is no
      longer possible, even with the assistance of the latest hearing aids. For most
      adults, deafness is a postlingual phenomenon. Adults who were born deaf or who
      lost their hearing in childhood tend to be unsuitable for cochlear implantation.
      Up to the age of six years, however, children born deaf can benefit considerably
      from a cochlear implant. Children who are provided with a cochlear implant
      shortly after becoming deaf also have a good chance of being capable of learning
      and understanding speech.

PMID- 8273026
TI  - [Surgical treatment possibilities of middle ear hearing loss].
AB  - Otological surgery is performed under the operating microscope with special
      microinstruments. The introduction of new technical means such as the argon
      laser, equipped with a fiberoptic handpiece, and the sceeter microdrill have
      improved the results according to the statistic of Berne. An important aspect is
      the approach to the structures in the temporal bone. The classical retroauricular
      and endaural incisions are replaced whenever possible by the less traumatic
      transmeatal approach directly through the external ear canal without external
      skin lesion. Ear drum perforations and cholesteatomas with and without ossicular
      lesions are repaired by different types of tympano-ossiculoplasty. Destroyed
      ossicles are replaced by allogenic prostheses or homologous ossicles.
      Otosclerosis is treated by a 'small-fenestra' stapedotomy with insertion of a
      teflon-platinum wire piston. Bone conduction hearing aids with conventional
      mastoid vibrators can be replaced by more efficient bone-anchored hearing aids
      directly fixed in the skull. The teamwork between ear surgeon, audiologist and
      electronical engineer has turned out to be important for the implantation of
      hearing aids.

PMID- 8273027
TI  - [Hearing aid rehabilitation of hearing disorders in adults].
AB  - Hearing-aid provision is still partly a medical task, in spite of technological
      progress and a confusing variety of types and models of devices. The diagnosis of
      the underlying disease, the appreciation of the consequences of hearing loss and
      the counseling of the hearing impaired person are prerequisites of the treatment.
      The physician should try to determine the etiology of the hearing loss. Also, a
      state-of-the-art otologic examination should be performed and the physician
      should be sensitive to the psychological and social consequences of the patient's
      hearing loss. For the assessment of fitted hearing aids, basic knowledge of the
      technical background is required. To measure hearing-aid benefit in the ENT
      office, suprathreshold and speech audiometry are indispensable tools.

PMID- 8273029
TI  - [Quality assurance in transfusion medicine].

PMID- 8273028
TI  - [Misconduct in research and scientific dishonesty. The academic system of
      qualifications must be revised].

PMID- 8273030
TI  - [Acute laparoscopic surgery].

PMID- 8273031
TI  - [Interruption of pregnancy after prenatal diagnosis--obligation and failure to
      report].

PMID- 8273032
TI  - [Apparent decrease in the occurrence of anencephalus in Norway 1967-90].
AB  - The occurrence of anencephalus as reported to the Norwegian Medical Birth
      Registry has fallen from 4.9 per 10,000 births in 1967-71 to 2.7 in 1987-90. The
      decrease is particularly noticeable for births with a gestational length of 28
      weeks or more. On the other hand, there has been a significant increase in the
      number of cases of anencephalus with a gestational age less than 28 weeks. The
      occurrence of meningomyelocele has remained relatively stable throughout the same
      period. Ascertainment error could explain these contrasting trends, since cases
      of anencephalus detected on ultrasound screening may lead to early termination of
      pregnancy without notification to the Medical Birth Registry. Better routines for
      notification of malformations are needed to improve the basis for surveillance in
      Norway.

PMID- 8273033
TI  - [Cesarean section and quality assurance].
AB  - An increasing number of Caesarean sections at the maternity ward (17.1%) in 1991
      led to a retrospective analysis as part of the quality assurance at the clinic.
      The main indications were mechanical (21.7%), maternal (21.1%), foetal distress
      (20.5%) and foetal presentation (19.4%). After procuring a new cardiotocograph at
      the clinic, with ST-analysis, reintroducing monthly cardiotocography meetings and
      adopting a more critical attitude towards performing Caesarean section, the rate
      decreased to 12.2% in 1992.

PMID- 8273034
TI  - [Primary sclerosing cholangitis. Illustrated by an unselected hospital material].
AB  - During the period from 1985 to 1993 primary sclerosing cholangitis was diagnosed
      in 16 patients, five females and 11 males, mean age 43 years. 12 of the patients
      (75%) had inflammatory bowel disease. Among 262 patients with ulcerative colitis,
      cholangitis was found in ten, whereas the disease was diagnosed in only two
      (1.9%) of the 108 patients with Crohn's disease. In eight patients (50%) no
      progression of the cholangitis was observed. However, six patients (38%) died
      during the observation period, three 19% due to cholangiocarcinoma and one due to
      liver failure. Cholangiocarcinoma is frequently found in patients with primary
      sclerosing cholangitis. A mortality of 38% indicates a serious clinical course in
      many patients.

PMID- 8273035
TI  - [Spontaneous esophageal rupture. Differential diagnosis from acute myocardial
      infarction].
AB  - Chest pain is a common cause of hospitalization. Occasionally, chest pain is due
      to spontaneous perforation of the oesophagus, a dangerous condition that is often
      misdiagnosed. This case illustrates different aspects of Boerhaave's syndrome. In
      patients with chest pain of uncertain etiology, chest radiographs or CT scan of
      the thorax should be performed. If pneumo-(hydro) thorax and/or mediastinal air
      is observed, oesophageal contrast studies must be carried out to verify
      perforation of the oesophagus. The preferred treatment is immediate operation and
      closure of the defect.

PMID- 8273036
TI  - [Lupus vulgaris. Cutaneous tuberculosis in a Vietnamese refugee].
AB  - Since 1990 there has been a slight increase in the number of cases of
      tuberculosis in Norway. Tuberculosis can affect the skin with or without apparent
      involvement of internal organs. A case of lupus vulgaris in a 13 year-old male
      Vietnamese refugee is described. The Pirquet test was strongly positive. However,
      no involvement of lungs or other internal organs was found. Clinical remission
      was achieved using isoniazide and rifampicin.

PMID- 8273037
TI  - [Hybris and crisis. The 19th century and transition to modern medicine].
AB  - Medicine declared itself to be a scientific discipline in the 19th century, and
      radically cut off its former links with the Hippocratic-Galenic tradition after
      the French Revolution in 1789. Owing to the great progress made in physics and
      chemistry, these disciplines came to be regarded as the only ones capable of
      solving medical problems. This is a reductionist view, in contrast to the
      vitalist view, which still believed in the existence of the Hippocratic physis or
      life force. Reductionist medicine led to great advances, though in the 19th
      century much of the wisdom of earlier times tended to be forgotten, to the
      detriment of medicine as a whole. It was believed that medicine and science could
      solve all the world's problems, a belief that, in modern times, has been
      abandoned as invalid. We now need a new medical anthropology, or rather medicine
      that is anthropological in its thinking.

PMID- 8273038
TI  - [Psyche and soma--Descartes in our hearts?].
AB  - The essay deals with the mind-body problem. The first part describes the
      different views held by philosophers from Plato up to modern times, stressing the
      standpoint of Rene Descartes for medical philosophy and dualism. The author
      outlines the new research field of psychoneuroimmunology, and asks whether this
      could be one of the keys to the mind-body problem. The concept of anomaly is
      discussed, taking placebo and nocebo as prominent examples. Finally the author
      outlines modern holistic thinking based on a general systems theory, with biology
      as a dynamic interplay of culture, ecology, mind, and body in an open non-lineary
      system.

PMID- 8273039
TI  - [Sclerotherapy of spermatoceles and hydroceles. Long-term results of polidocanol
      use].
AB  - Treatment of hydroceles and spermatoceles with evacuation, followed by injection
      of the sclerosing agent Polidocanol 3% (Aetoxysklerol), is a simple, low cost
      alternative to surgery. For the patient, it is also less painful compared to
      sclerotherapy using tetracycline. This article shows that the long term results
      are very promising. 28 patients, of whom two were treated for bilateral celes,
      gave us a total of 30 treatments. We interviewed the patients 62 months (52-67
      months) after treatment, and found that in 24 of the 30 treatments there were no
      sign of relapse. In three cases the patient had noticed a small relapse, but had
      no pain. Three have later been treated with surgery.

PMID- 8273040
TI  - [Dishonesty in medical research. A questionnaire study among project
      administrators in Health Region 4].
AB  - During the period 1986-92, a questionnaire survey was conducted among research
      project administrators whose study protocols were assessed by the ethical
      committee for biomedical research in Health region 4 (Central Norway). The
      questions referred to the scientists' attitudes towards medical research ethics
      in general, and their views on the work of the committee. They were also asked to
      comment on seven statements about scientific fraud and misconduct. This paper
      presents data on misconduct from the 119 scientists who completed the
      questionnaire, i.e 70% of the 159 recipients. Some 40% claimed that scientific
      fraud is a problem in Norway, but 46% maintained that it is less so than in other
      countries. More than every fourth researcher (27%) knew of one or more cases of
      scientific misconduct, 42% stated that their knowledge was not publicly known.
      18% felt that they had been exposed to misconduct themselves. A majority (60%)
      stated that a better system is needed to investigate claims of scientific fraud.
      The authors discuss these findings in relation to the personal characteristics
      and scientific qualifications of the researchers, and the current knowledge about
      the extent of scientific fraud in medicine.

PMID- 8273041
TI  - [External cephalic version of breech presentation].
AB  - External cephalic version of the breech presentation has long traditions. Earlier
      this was practised to improve the baby's prognosis. Today most breech
      presentations are delivered by Caesarean section, and external cephalic version
      of the breech presentation is done to reduce the number of Caesarean sections.
      External cephalic version of breech presentation reduces the total rate of
      Caesarean sections by 1-2%. If the breech deliveries are carefully selected at
      term, they become comparable with cephalic presentation, both in terms of
      mortality and morbidity. Although the complications associated with external
      cephalic version of the breech presentation are considered minimal they cannot be
      ruled out. Therefore systematic external cephalic version of the breech
      presentation should not be encouraged.

PMID- 8273042
TI  - [External national quality control of blood group typing 1983-92. Significance
      for quality assurance in transfusion medicine].
AB  - A programme for external quality control in blood group serology has been run in
      Norway since 1983 by the National Institute of Public Health. Uncomplicated AB0
      and Rh(D) grouping, including Du typing, has been performed satisfactorily. Rh(D)
      grouping of presensitized, Rh (D) negative cells is still a problem, but one
      which has been reduced significantly. Both indirect and direct antiglobulin
      reactions have given about 15% false negative results, mainly with weak
      antibodies and weakly sensitized cells. Poor training of technicians in reading
      weak agglutination reactions may be an important source of error. The importance
      of post-graduate training of blood bank staff is emphasized.

PMID- 8273043
TI  - [Fibromyalgias--we should use our experiences].

PMID- 8273044
TI  - [Prednisolone-induced obsessive-compulsive behavior in a child].

PMID- 8273045
TI  - [A computer program for simulation of two-group experiments].

PMID- 8273046
TI  - [Vascular surgery in Norway].

PMID- 8273047
TI  - [Mental disorders increase length of stay and use of resources in somatic
      hospitals].

PMID- 8273048
TI  - [Infrared tympanic thermometry--worse than reported?].

PMID- 8273049
TI  - [Physicians who come to Norway as refugees].

PMID- 8273050
TI  - [Self evaluation of prescription practice].

PMID- 8273051
TI  - [Russia is not a country, not a nation, but a thousand years old disease].

PMID- 8273052
TI  - [It is better to prevent than to treat, but do we know how?].

PMID- 8273053
TI  - [Prioritizing is a solution--but of which problems? When physicians are
      transferred from a "good" team to a "bad" one].

PMID- 8273054
TI  - [With DNA at the court].

PMID- 8273055
TI  - [Myocardial scintigraphy. Is Norway sufficiently supplied?].

PMID- 8273056
TI  - [Thallium scintigraphy in the diagnosis of coronary disease].
AB  - A retrospective analysis was performed in 371 patients who underwent stress
      thallium scintigraphy over a three-year period. The patient-group was highly
      selected. The majority had normal or uninterpretable exercise EKG. The purpose
      was to assess the clinical value of thallium scintigraphy, and to determine the
      accuracy of the test compared with coronary arteriography for diagnosis of
      coronary artery disease in 108 of the patients who had undergone cardiac
      catheterisation. For 79 patients (73%), the scintigraphic results were in
      complete accordance with the coronary arteriograms. Furthermore, critical review
      of the arteriograms showed discrete stenosis of less than 50% in another 12 of
      the patients with abnormal scans. This yields an overall diagnostic accuracy of
      84%. The authors discuss some limitations of the method and possible causes of
      "false" perfusion defects. The results of the analysis are consistent with
      earlier reports, and emphasize thallium scintigraphy as a valuable diagnostic
      tool in coronary heart disease.

PMID- 8273057
TI  - [Are the results of thallium scintigraphy and coronary angiography equivalent? An
      evaluation of thallium scintigraphies performed at Vestfold Central Hospital].
AB  - The value of exercise-redistribution thallium-201 perfusion scintigraphy (SPECT;
      single photon emission computed tomography) in the diagnosis of coronary artery
      disease was evaluated in 23 patients (one patient tested twice) who were
      subsequently submitted to coronary angiography. Reversible perfusion defects
      indicating myocardial ischemia were found in 22 patients, of whom 18 had
      angiographically significant coronary artery stenoses. Two patients had negative
      thallium scans, one had a normal angiogram and one had single vessel disease.
      Thus 18 of 19 patients with angiographically verified coronary heart disease had
      a positive thallium scan. The majority of patients with left main stenosis and
      triple vessel disease had scintigraphic evidence of double or triple vessel
      disease. The scintigraphic method identified the correct anatomical localization
      in 73% of the angiographically verified coronary artery stenoses. In conclusion,
      a positive exercise-redistribution thallium scan had a high predictive value in
      the diagnosis of coronary artery disease, whereas its value in estimating the
      number and localization of stenoses was more limited.

PMID- 8273058
TI  - [Encopresis--in a child psychiatric treatment regime].
AB  - The evidence to date suggests a multi-factoral aetiology for encopresis,
      especially in cases where it is part of a psychiatric disorder. A physiological
      predisposition, the age at which bowel training is begun, the parent-child
      relationship and environmental stresses are influential. Thus no single treatment
      will suffice for the varieties of encopresis encountered in child psychiatric
      practice. This paper presents a programme used at a child psychiatric unit and
      embodying several methods of treatment: use of lavement, laxatives and softeners,
      counselling, behaviour modification and environmental therapy.

PMID- 8273059
TI  - [Retroperitoneal chylous cyst].
AB  - In pathology, cysts of the retroperitoneum are usually classified together with
      omental and mesenteric cysts. Because of risk of complications and malignancy
      these cysts should be extirpated. The frequency of complications and recurrence
      after surgery is significantly higher for retroperitoneal cysts than for the
      other types mentioned above. We describe a patient with a retroperitoneal chylous
      cyst of three litres. Correct diagnosis was made by CT-scan and chemical analysis
      of cyst fluid prior to surgery. The cyst was removed completely using an
      intercostal, retroperitoneal approach. The postoperative course was uneventful,
      and no evidence of recurrence was found after six months.

PMID- 8273060
TI  - [Allogeneic bone marrow transplantation in adult patients with serious
      hematological diseases 1985-1992].
AB  - We present updated results from allogeneic bone marrow transplantation in adult
      patients who received transplants between 1985 and 1992. Of 47 patients, 36 where
      disease-free survivors 8-93, mean 32 months after transplantation. Of these,
      seven had received marrow from unrelated donors. The present treatment capacity
      is insufficient to cover the demand for allogeneic bone marrow transplants for
      Norwegian patients.

PMID- 8273061
TI  - [DNA profiling for identification purposes].
AB  - DNA "fingerprinting" was described for the first time in 1985, and since then DNA
      profiling has been used increasingly to identify the origin of biological
      material, such as blood and semen stains. The method is also used in cases of
      disputed paternity and to help identify dead bodies. In this article we review
      the methods and their practical use, and discuss various aspects of quality and
      security.

PMID- 8273062
TI  - [Prioritizing and righteousness--what do we do when we can't do everything?].
AB  - This article considers the principles for allocating scarce resources in the
      health care sector. The author discusses the conflict between the utilitarian
      principle of welfare maximization and the norm of equality. It is argued that the
      goal of equal health may lead to the problem of "the bottomless pit". That is to
      say, an unreasonable amount of the total health care resources will be
      distributed to those with the most severe conditions. The utilitarian principle
      leads to a more efficient distribution of resources, but in some important cases
      may conflict with the concern for equality or the concern for those who are worst
      off. The problem seems to be that the norm of distributive efficiency and the
      norm of distributive equality are both relevant in society. John Broome's account
      of fairness as equal proportional satisfaction of legitimate claims is presented
      as an interesting approach to this problem. A classification of criteria is also
      presented as a general framework for a debate on the making of priorities in the
      clinical setting.

PMID- 8273063
TI  - [Hypoplastic left heart syndrome. Present experiences and future possibilities].
AB  - The authors report experiences from Norwood's staged palliation for hypoplastic
      left heart syndrome performed in Philadelphia on Norwegian children. Although
      there is no universal agreement that these children should be operated at all,
      the Norwegian health authorities have decided that all expenses for transport,
      examination and treatment shall be covered by the National Health Insurance
      Scheme. Since 1987 a total of 21 children have been transported to USA for
      operation. Eight of these children have completed all the planned stages of the
      operative treatment. Two are waiting for stage 3. 11 children have died. The
      authors discuss how to proceed with regard to treatment of this complicated
      patient group in future.

PMID- 8273064
TI  - [Ultrasonic assessment of gestational age and prolonged pregnancy].
AB  - The benefits of routine use of ultrasound dating of pregnancy have been
      questioned. With ultrasound dating, the expected date of delivery is often
      postponed later than calculated. This means that true post-term pregnancies may
      be undetected and second-trimester determination of gestational age could
      represent a risk to the infants' health. This possibility has been assessed in a
      population of ultrasound screened women with optimal conditions for dating the
      pregnancy by Naegeles rule. No perinatal complications due to undetected post
      term pregnancies were found.

PMID- 8273065
TI  - [Recommendations of the Council for Nutrition on infant nutrition. Norwegian
      National Nutrition Council].
AB  - Because of the high frequency of nursing mothers there is concensus that, in
      general, the diet of Norwegian newborns is good for the first six months of life.
      However, several publications have questioned the recommendations concerning the
      babies' diet from the age of six to 12 months with respect to time of weaning and
      introduction of cow's milk, and intake of energy, fat-soluble vitamins, iron and
      essential fatty acids. The Norwegian National Nutrition Council has therefore
      evaluated the available data, and has adjusted some of the recommendations,
      including the recommendations for energy intake, energy percent from fat and
      essential polyunsaturated fatty acids.

PMID- 8273066
TI  - [Is the main goal of the health care services to produce health?].
AB  - A questionnaire on the relative weight attached to severity of disease and health
      gain when allocating scarce resources between patient groups was answered by 99
      doctors in general practice. The same questionnaire had been previously answered
      by politicians. Doctors and politicians alike tended to emphasize severity of
      disease rather than health gain when allocating scarce resources. Furthermore,
      many did not emphasize either of these factors, but distributed the resources
      equally between the different patient groups. If the patients were equally ill,
      the doctors attached greater weight than the politicians did to health gain. The
      answers to the questionnaire indicate that the obligation to help the most
      seriously ill and to uphold the ideal of equality are regarded as more
      fundamental than the goal of producing health effectively.

PMID- 8273067
TI  - [Impossible office conditions for assisting physicians at the new
      Rikshospitalet].

PMID- 8273068
TI  - [Treatment (and diagnosis) of menorrhagia].

PMID- 8273069
TI  - [Norway, an acyclovir-free region?].

PMID- 8273070
TI  - [Prioritizing in practice. Thinking about it, wishing it, then doing it!].

PMID- 8273071
TI  - [Not wearing seat belts is expensive!].

PMID- 8273072
TI  - [Thrombin-mediated anticoagulation. The protein C/protein S/thrombomodulin
      system].

PMID- 8273073
TI  - [Treatment of anal cancer].

PMID- 8273074
TI  - [Treatment of anal cancer in Trondelag].
AB  - We have retrospectively examined the medical records and prospectively studied
      the survival of 43 patients (37 women and six men) treated for anal cancer in the
      Trondelag region of Norway during the period 1970-89. During this period,
      different strategies were used, ranging from primary surgery to combined chemo
      radiotherapy and sphincter saving therapy. 20 patients were treated with surgery
      alone, nine patients first with surgery and postoperatively with irradiation
      because the surgery was non-radical (histologic), and 14 patients with combined
      chemo- and radiotherapy. The five year cancer ani-specific survival in the whole
      group is 69%. The predicted five year survival in the chemo-radiotherapy group is
      90% versus 61% in the group treated with surgery. Primary chemotherapy combined
      with radiotherapy should be the preferred treatment for carcinoma of the anal
      canal.

PMID- 8273075
TI  - [Etiology and pathogenesis of spontaneous venous thromboembolism].
AB  - Thromboembolic disease is a major clinical problem. This article reviews the
      etiology and pathogenesis of spontaneous venous thromboembolism. There is an
      association between thromboembolism and hereditary deficiency of antithrombin
      III, protein C or protein S. In young patients, impaired fibrinolytic activity
      may represent the most common haemostatic abnormality associated with thrombosis.
      Dysfibrinogenaemia has been related to thrombotic disease in some patients.
      Moreover, the presence of phospholipid directed antibodies is associated with
      thrombosis in patients with connective tissue disorders. Therefore, for young
      patients with spontaneous thromboembolic disease, a thorough laboratory
      investigation is recommended.

PMID- 8273077
TI  - [Achalasia. Diagnosis and therapeutic effect evaluated by esophageal manometry].
AB  - Achalasia was diagnosed in 57 patients from 1982 through 1991. 13 patients were
      evaluated by manometry both before and after pneumatic dilatation of the
      sphincter. There were no serious complications. All but one patient experienced
      good symptomatic effect; one patient was operated after two ineffective
      dilatations. The tonus and length of the lower oesophageal sphincter decreased
      significantly, but dilatation did not improve the swallow-induced relaxation of
      the sphincter, nor peristalsis in the oesophageal body. In three randomly
      selected patients, transcutaneous nervous stimulation did not have any
      symptomatic effects, nor did it affect the motility pattern of the oesophagus.
      Pneumatic dilatation of the lower oesophageal sphincter is a safe and effective
      first-choice treatment for achalasia, with myotomy being reserved for patients
      whose symptoms are not relieved successfully after two dilatations.

PMID- 8273076
TI  - [Familial protein S deficiency].
AB  - Protein S deficiency is an autosomal dominant inherited disease. The authors
      describe a family in which 27 of the 52 members had a deficiency of S protein.
      Eight family members have suffered from thromboembolic disease.

PMID- 8273078
TI  - [The concept of health in the perspective between description and evaluation].
AB  - Discourse on the concepts of health and disease is characterized by the
      differences between two main perspectives: the biostatistic and the holistic.
      This paper describes some of these differences and aims at showing how they can
      illuminate the ongoing debate on criterions for deciding priorities in the health
      services. It is argued that the basic perspective of The Lonning Committee (a
      Government appointed committee to consider criterions for making priorities in
      the medical sector) is holistic, and that its report illustrates how a society
      forms its own practical and evaluative concept of health. This concept seems to
      be based on a complex medical, social and cultural fundament rather than on a
      strictly biomedical one.

PMID- 8273079
TI  - [Standardization, control and approval of surgical implants in Europe].
AB  - The "new approach" policy limits the European Community legislative harmonization
      to adopting essential safety requirements which medical devices brought on the
      market will have to meet, and thereafter obtaining free trade in the European
      market. A set of harmonized standards will explain in detail what the essential
      requirements mean in practice. Therefore, the work being done on standards for
      surgical implants by the European Committee for Standardization (CEN) is
      indispensable. The impact of the "New Approach" on the Norwegian legislation is
      discussed, and it is concluded that the Committee for Single-Use Medical Devices,
      which registers all surgical implants prior to marketing in Norway, will have to
      close down in 1995.

PMID- 8273080
TI  - [Changes in sales of estrogens 1989-1992. Effects of a national consensus
      conference?].
AB  - In November 1990 a consensus conference was held in Norway on the use of
      oestrogens for perimenopausal and postmenopausal complaints, and for preventive
      purposes. The sales statistics reveal an increase in sales of drugs for hormone
      replacement therapy after the conference, but the trend had already started
      before the conference was held. We found the conference had had a statistically
      significant impact on sales of some of the drugs. We also collected information
      on marketing campaigns before and after the conference. Only a modest change was
      found in marketing efforts by the pharmaceutical industry. Presentations in the
      media were considered to have a strong impact on oestrogen promotion.

PMID- 8273081
TI  - [Principles for control of severe meningococcal disease].

PMID- 8273082
TI  - [Do we kill our cardiac patients with statin therapy?].

PMID- 8273083
TI  - [Hospitalization in cases of fetal death].

PMID- 8273084
TI  - [A digital diary for diagnostic lists].

PMID- 8273085
TI  - [Self-control of physicians' charges].

PMID- 8273086
TI  - [AIDS information in Zimbabwe].

PMID- 8273087
TI  - [Continuing education at local hospitals--what now? Consequences of downgrading
      surgical departments in North-Norway].

PMID- 8273088
TI  - [Computer ECG--the technology is new, but is it useful?].

PMID- 8273089
TI  - [Computer technology and electronic medical records in hospitals].

PMID- 8273091
TI  - [Treatment of meniscal injuries--current status].

PMID- 8273090
TI  - [The price of development].

PMID- 8273092
TI  - [Follow-up of sutured meniscus by means of survival analysis].
AB  - We describe a retrospective study of patients operated by meniscal suture at our
      hospital from 1986 through 1992. 63 patients were operated, 50 males and 13
      females. Mean age was 26 years. Complete data were retrieved at follow-up for 57
      patients. Mean observation time was two years. 90% were operated using the
      arthroscopical technique. 25 patients have been re-operated because of meniscal
      rerupture. The cumulative survival rate was 44% five years after operation.
      Survival analysis revealed no significant differences by variables such as sex,
      age, instability and lateral or medial location revealed. Experienced surgeons
      achieved only insignificantly better long-term results than did trainees. There
      was no significant difference in healing rate between displaced bucket-handle and
      non-displaced tears, nor between chronic and acute tears.

PMID- 8273093
TI  - [Electroconvulsive treatment in parkinsonism].
AB  - This article describes three patients with different causes of parkinsonian
      syndromes where electroconvulsive treatment markedly improved their symptoms. The
      results are discussed and compared with those of previously published studies.
      Most of these studies, however, have substantial methodological shortcomings. The
      mechanism inducing the improvement is unknown, but could possibly be increased
      postsynaptic dopamine function. The literature indicates that electroconvulsive
      treatment has antiparkinsonian effects independent of any effect on mental state.
      We suggest that patients with parkinsonian syndromes, who respond
      unsatisfactorily to conventional therapy, as well as patients who develop severe
      neuropsychiatric manifestations, should be considered for a course of
      electroconvulsive treatment.

PMID- 8273094
TI  - [Human herpesvirus 6].
AB  - Human herpesvirus-6 (HHV-6) is the most recently discovered herpesvirus. It
      shares several characteristic properties with the other herpesviruses; the genome
      is large, consisting of approximately 170,000 base pairs and potentially
      containing more than 70 genes. The virus also probably forms latent infections in
      the host. It is widely distributed in the population, and seropositivity reaches
      60-90% by the age of two. HHV-6 is associated with the childhood disease
      exanthema subitum, and probably also causes heterophile antibody-negative
      mononucleosis. Our present knowledge about the virus is reviewed.

PMID- 8273095
TI  - [Tuberculosis and HIV infection in the Kweneng district, Botswana].
AB  - The prevalence of HIV infection in a group of Botswana tuberculosis patients was
      studied in a linked, anonymous survey that included 214 cases. The testing was
      done by ELISA serology. 45 of 214 patients (21%) were HIV positive. The HIV
      seropositivity reached 29% in the age group 15-49 years. 25% of the females
      (average age 34 years) and 18% of the males (average age 39 years) were HIV
      positive. 18 (40%) of the 45 HIV positive patients had AIDS. No significant
      differences were found between HIV positive and HIV negative patients with regard
      to clinical type of tuberculosis. The findings are discussed in relation to other
      studies from Africa.

PMID- 8273096
TI  - ["Wise Men confound the World!". A district physician's struggle against
      superstition and sorcery in the 19th century].
AB  - When Michael Krohn (1822-97) was appointed district physician in Ytre
      Nordhordland in 1855 he had to fight hard against local witchcraft. Health
      education became his main strategy. He gave a series of lectures to the local
      Board of Health and also invited the schoolteachers to the meetings. The
      prejudiced local politicians neglected the school system and actively opposed the
      propositions he put forward. Nevertheless, a generation later the witches had
      disappeared. Health education can take some credit for this result, but probably
      the most important factor was simple trust.

PMID- 8273097
TI  - [Birth of clinical practice--in a historical perspective].
AB  - Modern medicine is rooted in the science and the clinical practice of the 18th
      and 19th century. Here it finds its aims and methods, its view of life and death,
      and of health and disease. The french philosopher Michel Foucault has made an
      original contribution to the understanding of the social and cultural aspects of
      the development of medicine. He seeks its foundation in the classificatory
      medicine of the nosology of the 18th century. The diseases were then organized in
      a botanical model by their essence. The doctor revealed and confirmed the natural
      development of the diseases. He practised an art of medicine founded on local
      conditions. Following the social and political demands for regulation in the 18th
      century, the first grand hospitals were built. Here the doctors had the
      opportunity to study a large number of patients, and the statistical methods led
      to a bloom of clinical medicine. However, before medical science was able to use
      the microscope, before it could find the solution to life and disease in the
      obduced body, much had to change. Man had to alter his view of life and death, of
      subject and object, of doctor and patient. Only then was it possible to carry out
      pathological anatomy. Michel Foucault has presented a view of the history of
      medicine which counterbalances deterministic management of the Asclepian heritage
      by science.

PMID- 8273098
TI  - [New treatment of psoriasis with the vitamin D analogue calcipotriol].
AB  - A new topical treatment for psoriasis was introduced in 1992 when the vitamin D
      analogue calcipotriol was registered in Norway. This is a new therapeutic
      principle for psoriasis. Calcipotriol induces differentiation and inhibits
      proliferation of the keratinocytes. Application twice daily for 6-8 weeks gives a
      60-70% improvement in plaque type psoriasis. No serious side effects have been
      reported when using up to 100 grams of the ointment weekly.

PMID- 8273099
TI  - [The requirement to use the cheapest synonymous preparation--does it work as
      intended?].
AB  - A retrospective analysis of all prescriptions for hypersensitive drugs was
      undertaken at a pharmacy serving 20 general practitioners and 17 temporarily
      employed doctors. The analysis was carried out in 1992 over two three-month
      periods separated by an interval of five months. The Governmental regulations
      aimed at promoting use of the "cheapest synonymous drug" apparently had little
      impact on the doctors' prescriptions. During the 11 months concerned, the
      prescribed antihypersensitive drugs contained an increasing share of expensive
      alternatives with no documented ability to reduce cardiovascular morbidity or
      mortality.

PMID- 8273100
TI  - [The role of the general practitioner in health care].
AB  - The World Health Organization is endorsing the Statement of WONCA, the World
      Organization of Family Doctors: "The considerations are consistent with the
      principles and policy of WHO." All WONCA's national member organizations have
      welcomed the Statement. The Statement seems to have already influenced the
      planning of health services in some countries and has been translated into
      several languages. High quality primary health care depends on the availability
      of well trained general practitioners as members of health care teams in the
      community. To this end, responsible authorities and the World Health Organization
      should adopt policies that will increase the number of trained physicians in
      general/family practice. Such policies will involve placing greater emphasis on
      primary medical care in medical schools, creating better opportunities for
      postgraduate training and research in general/family practice, and providing
      greater incentives for new graduates to choose a career in general practice. One
      of the requirements is strong departments of general practice/family medicine at
      all medical schools. With the aim of encouraging the training of more general
      practitioners/family physicians, this document outlines their role in the health
      care system and the knowledge, skills, and attitudes required.

PMID- 8273101
TI  - [Health survey in Finnmark--health status and risk of cardiovascular diseases
      among fishermen. A survey performed within the Health and Inequality program in
      Finnmark].
AB  - Fishermen were compared with other males aged 30-62 for various risk factors
      associated with arteriosclerotic heart disease. The set of data originated from a
      population study in Finnmark County, Norway. Risk of infarction was higher among
      fishermen; they had significantly higher mean total cholesterol values, drank
      more coffee and less low fat milk, and smoked more cigarettes. The analyses
      revealed, however, a marked variation in risk profile by geographical region. A
      striking reduction in risk of infarction has been experienced among the male
      population of Finnmark during the last 15 years, with fishermen apparently
      lagging somewhat behind. The authors discuss possible explanations for this
      reduction, and preventive strategies relevant to fishermen.

PMID- 8273102
TI  - [When liberalism becomes fanaticism].

PMID- 8273103
TI  - [Blood glucose level is everything! But at what HbA level should therapy be
      considered?].

PMID- 8273104
TI  - [HIV survey].

PMID- 8273105
TI  - [International cooperation in research in alternative medicine].

PMID- 8273106
TI  - [Can health services be distributed better in Africa? WHO's 43rd Regional
      Committee for Africa].

PMID- 8273107
TI  - [Computer technology and medical records in hospitals].

PMID- 8273108
TI  - [A square peg in a round hole? Who should have the responsibility for our
      continuing education and how should it be?].

PMID- 8273109
TI  - [Narcolepsy in horses].
AB  - Narcolepsy is an incurable non-progressive disease of the central nervous system.
      In humans, narcolepsy causes excessive drowsiness during the day (sometimes a
      sleep-attack occurs), cataplexy (sudden loss of muscle tone), hallucinations, and
      sleep paralysis. In the horse and other mammals cataplexy is the most frequently
      observed symptom. Excessive drowsiness can occur but is harder to observe.
      Cataplexy is caused by a fragmentation of the REM sleep. The etiology of
      narcolepsy is still subject to debate, partly because normal sleeping patterns
      are poorly understood. In humans and certain breeds of dogs a hereditary
      background has been demonstrated. In Shetland ponies the disease runs in certain
      families. The role of trauma and infection is the subject of debate. Cataplexy
      (which can be induced by physostigmine injection) confirms the diagnosis. Several
      drugs are available for the treatment of narcolepsy in humans. However there are
      a few data on the results of treatment of narcolepsy in the horse.

PMID- 8273111
TI  - [Regulation Commercial Control of Animal Diseases. A regulation from and for
      commerce].

PMID- 8273110
TI  - [Control of animal morbidity in Belgium and The Netherlands; where lies the
      border?].

PMID- 8273112
TI  - Biosynthetic studies of marine lipids. 42. Biosynthesis of steroid and
      triterpenoid metabolites in the sea cucumber Eupentacta fraudatrix.
AB  - The saponins, conjugated sterols, and free sterols of the sea cucumber Eupentacta
      fraudatrix were examined. A total of 85 steroids, twelve of them new, were
      identified in the free sterol, sulfated sterol, and sterol-xyloside fractions.
      The free sterol fraction contained 4 alpha,14 alpha-dimethylcholest-9(11)-en-3
      beta-ol(6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol(7) together with 18
      minor sterols. Examination of the aglycone moieties of the sterol-beta-xyloside
      fraction afforded 31 different sterols. Cholestan-3 beta-ol (15) and 24
      methylcholesta-7,22-dien-3 beta-ol (20) were the major sterols in this group.
      Cholestanol sulfate (74) and cholesterol sulfate (64) were identified as the
      major components among the 34 different sterol sulfates present. Finally,
      cucumariosides G1 (1), C1 (2), C2 (3), H (4), and G2 (5) were isolated from the
      saponin fraction. Radiolabeling experiments indicated that there are two pathways
      of sterol biosynthesis in E. fraudratix. The first involves transformation of
      squalene to produce lanosta-9(11),24-dien-3 beta-ol(parkeol) which is
      subsequently demethylated to form 4 alpha,14 alpha-dimethylcholest-9(11)-en-3
      beta-ol (6) and 14 alpha-methylcholest-9(11)-en-3 beta-ol (7). The second
      proceeds through squalene to lanosterol which is further metabolized to produce
      the triterpene saponins, 5 alpha-cholest-7-en-3 beta-ol (19) and its xyloside
      (49).

PMID- 8273113
TI  - Synthesis and structure-activity relationships of 14 beta-hydroxy-5 alpha
      pregnanes: pregnanes that bind to the cardiac glycoside receptor.
AB  - 5 alpha-pregnane-3 beta,14 beta,20 beta-triol 3-alpha-L-rhamnopyranoside (8) and
      3 beta-(alpha-L-rhamnopyranosyloxy)-5 alpha-pregn-14-en-20-one (14) were prepared
      from uzarigenin by ozonolysis followed by zinc and acetic acid reduction and
      glycosidation. During the glycosidation reaction leading to (8) the corresponding
      ortho ester (9) was also obtained. Uzarigenin alpha-L-rhamnopyranoside (15) also
      was prepared. Synthesis of 5 alpha-pregnane-3 beta,14 beta,20 beta-triol (20) is
      described. Structures were established by analysis of their NMR spectra. The
      binding affinity of 5 alpha and 5 beta cardenolide and pregnane derivatives as
      measured in a radioligand binding assay was determined and their structure
      activity relationships compared. The receptor binding affinity of the 5 alpha
      derivatives is less than that of the corresponding 5 beta derivatives.

PMID- 8273114
TI  - Synthesis of 7- and 12-hydroxy- and 7,12-dihydroxy-3-keto-5 beta-cholan-24-oic
      acids by reduction of 3,7-, 3,12- and 3,7,12-oxo derivatives.
AB  - 7 alpha-, 12 alpha-, 12 beta-Hydroxy and 7 alpha,12 alpha- and 7 alpha,12 beta
      dihydroxy-3-ketocholanoic acids were prepared in satisfactory yields protecting
      the 3-keto group as dimethyl ketal and subsequent reduction with sodium
      borohydride of the corresponding 7- and 12-oxo functionalities. The same
      procedure gave also 3,12-diketo-7 alpha-hydroxy-cholanoic acid.

PMID- 8273115
TI  - Synthesis and aromatase inhibition by potential metabolites of exemestane (6
      methylenandrosta-1,4-diene-3,17-dione).
AB  - Exemestane (6-methylenandrosta-1,4-diene-3,17-dione; FCE 24304) is an orally
      active irreversible aromatase inhibitor which is in phase II clinical evaluation
      for the potential therapy of postmenopausal breast cancer. A series of exemestane
      analogs, with modifications at the 6-methylene group and with additional
      reduction at the 17-keto group, were synthesized as potential metabolites and
      tested in vitro for their effect on human placental aromatase. All these new
      analogs were found to be less potent in inhibiting aromatase than exemestane. The
      most effective compound was the 17 beta-hydroxy-derivative (compound 2), which is
      2.6-fold less potent than exemestane [50% inhibitory concentration (IC50) 69 and
      27 nM, respectively]. The various C-6 modified derivatives of the 17-oxo series
      were found to inhibit the aromatase enzyme in the following descending order: 6
      methylene (exemestane) > 6-spirooxirane (6) > 6 beta-hydroxymethyl (11) > 6
      hydroxymethyl (7) > 6 beta-carboxy (13), showing IC50 values of 27, 206, 295,
      2,300, and 7,200 nM, respectively. The 17 beta-hydroxy analogs of some of the
      above mentioned compounds were also synthesized (3,4,12) and found to be 3-8-fold
      less potent than the corresponding 17-keto analogs.

PMID- 8273116
TI  - Chiral hydrogenation of estrone-3-methyl ether on modified Raney nickel
      catalysts.

PMID- 8273117
TI  - Serum corticosteroid-binding globulin levels in children undergoing heart
      surgery.
AB  - Serum corticosteroid-binding globulin (CBG) levels were measured in children
      (mean age 4 years) during heart surgery. Considerable decrease in CBG level
      occurred between baseline examination (416 +/- 39 nM) and the day of surgery (314
      +/- 30 nM). Relatively simple closed heart surgery did not influence CBG level
      with maximal cortisol level being 20 +/- 4 micrograms/dl. Open heart surgery
      under conditions of profound hypothermia (26 C, without extracorporeal
      circulation) caused dramatic lowering of CBG level, particularly striking after
      resuscitation (180 +/- 20 nM). At the same time cortisol level reached extremely
      high values (78 +/- 8 micrograms/dl). These data suggest that CBG is likely to
      play an important role in pituitary-adrenal response to surgery under severe
      conditions of hypothermia and cardiac arrest.

PMID- 8273118
TI  - Enzymatic O-methylation of catechol estrogens in red blood cells: differences in
      animal species and strains.
AB  - Enzymatic O-methylation of catechol estrogens in red blood cells has been
      investigated with respect to species difference. In the presence of S
      adenosylmethionine, 2- or 4-hydroxyestradiol (2-OHE2 or 4-OHE2) was incubated
      with blood lysate obtained from rats (five strains), guinea pigs, mice, rabbits,
      dogs, monkeys, and humans, respectively. The yielded guaiacols and unchanged
      substrate were determined by gas chromatography/mass spectrometry in a selected
      ion monitoring mode employing the corresponding 2H4-labeled compounds as internal
      standards. The total amounts of guaiacols formed from 2-OHE2 and 4-OHE2 were
      different, being the highest (79.6% and 38.1%) in monkeys and the lowest (5.1%
      and 1.9%) in humans. The ratios of isomeric guaiacols formed from 4-OHE2
      (4Me/3Me) were 7.6-71, while those from 2-OHE2 (2Me/3Me) were 1.4-3.2. Thus,
      marked differences in O-methylation of catechol estrogens were observed among
      animal species, but no significant strain difference was detected in rats.

PMID- 8273119
TI  - Effects of danazol on endometrial DNA synthesis in rats.
AB  - The suppressive effects of Danazol, an isoxazol derivative of the synthetic
      steroid 17 alpha-ethinyltestosterone, on endometrial DNA synthesis were
      investigated in rats by immunohistochemistry with bromodeoxyuridine (BrdU) and
      DNA-synthesizing enzyme assays. Rats treated with Danazol for 14 days at 17-19
      weeks of age showed a decrease of plasma gonadotropins associated with ovarian
      hypofunction, persistent diestrus, and a smaller number of corpora lutea in
      ovary, resulting in no BrdU-immunoreactive (S-phase) cells in endometrial
      epithelium and lower activity of thymidine kinase in the uterus compared with
      control.

PMID- 8273120
TI  - Sex hormones in male serum.

PMID- 8273121
TI  - Recombinant human erythropoietin and its role in transfusion medicine.

PMID- 8273122
TI  - Monitoring transfusionist practices: a strategy for improving transfusion safety.
AB  - BACKGROUND: Data from New York State indicate that about 1 of every 33,000 red
      cell units transfused is ABO-incompatible with the recipient. National
      application of these data suggests that as many as 360 ABO-incompatible whole
      blood and red cell transfusions might occur annually in the United States.
      Phlebotomy and blood bank laboratory errors cause some of these ABO-incompatible
      transfusions, but the greatest number result either partially or solely from the
      failure of transfusionists to identify properly either a patient or the blood
      component a patient receives. STUDY DESIGN AND METHODS: A quality
      assessment/quality improvement (QA/QI), process is described that allowed for the
      direct oversight (monitoring) of transfusionists' practices and for the
      assessment of institutional policies for blood administration. RESULTS: At the
      beginning of the QA/QI process, monitoring of blood administration practices
      revealed that a variance from institutional blood administration policy occurred
      during 50 percent of blood and component transfusions. As a result of the QA/QI
      process, the percentage of transfusions with an associated variance from
      institutional policy dropped to nearly zero. CONCLUSION: The QA/QI process
      described in this report, or one similar to it, could improve transfusion safety
      and serve as a model for increased involvement by transfusion service medical
      directors in the oversight of transfusionists' practices.

PMID- 8273123
TI  - Monocyte chemoattractant protein production in red cell incompatibility.
AB  - BACKGROUND: Mononuclear phagocytes play a central role in hemolytic transfusion
      reactions by erythrophagocytosis and production of inflammatory mediators.
      Factors that affect the number or function of monocyters would be expected to
      alter the clinical course of hemolytic transfusion reactions, and thus the
      production of monocyte chemoattractant protein-1 (MCP-1), a recently described
      chemotactic and activating cytokine specific for monocytes, was investigated in
      two distinct settings of red cell (RBC) incompatibility. STUDY DESIGN AND
      METHODS: Fresh heparinized whole blood was incubated with ABO-compatible or 
      incompatible RBCs. Isolated peripheral blood mononuclear cells were incubated
      with anti-D-coated or uncoated RBCs. MCP-1 was measured in the plasma or culture
      medium by enzyme-linked immunosorbent assay. MCP-1 gene expression was detected
      by Northern blot analysis of buffy coat or mononuclear cell total RNA. RESULTS:
      Significant levels of MCP-1 protein in plasma or medium were detected 24 hours
      after the addition of incompatible RBCs, but not in the first 6 hours. Nonimmune
      hemolysis of added RBCs did not stimulate MCP-1 production. The inactivation of
      complement by heat treatment of plasma prior to the addition of RBCs to whole
      blood did not prevent MCP-1 production. Nor did neutralizing antibodies to tumor
      necrosis factor prevent MCP-1 production in ABO incompatibility. MCP-1 production
      was associated with increased steady-state levels of white cell MCP-1 mRNA, which
      occurred more rapidly in ABO than Rh incompatibility. CONCLUSION: The monocyte
      specific chemotactic cytokine MCP-1 is produced by peripheral blood leukocytes in
      response to RBC incompatibility. MCP-1 may act in a positive feedback loop to
      recruit and activate monocytes during hemolytic transfusion reactions, thus
      contributing to the maintenance of these reactions.

PMID- 8273124
TI  - Cytokine generation in stored platelet concentrates.
AB  - BACKGROUND: Cytokines, because of the nature of their immunoinflammatory actions,
      are potential mediators of the symptom complex of nonhemolytic transfusion
      reactions. One possible source of cytokines in the transfusion setting is the
      stored blood component itself. STUDY DESIGN AND METHODS: To test this
      possibility, the plasma portion of stored platelet concentrates (PCs) was assayed
      for the presence of interleukins 1 beta (IL-1 beta), 6 (IL-6), and 8 (IL-8) and
      tumor necrosis factor alpha (TNF-alpha). Samples were taken from PCs obtained
      from the inventory of a regional blood center (n = 120; 30 each of 2-, 3-, 4-,
      and 5-day-old units). RESULTS: Detectable levels of IL-8 were measured in 59
      percent of the PCs sampled, ranging from 30 percent of the 2-day-old units to 83
      percent of the 5-day-old units. The median IL-8 concentration ranged from
      undetectable levels in 2-day-old units up to 1100 pg per mL in 5-day-old units.
      The mean IL-8 concentration in 5-day-old units, 11,600 pg per mL, was 100 times
      the mean for 2-day-old units, which was 116 pg per mL (p < 0.0001). The highest
      levels of IL-8, 50,000 to 200,000 pg per mL, in general were found in units with
      the longest storage times and highest white cell counts. Sequential sampling of
      17 individual PCs over 7 days of storage confirmed that IL-8 increases
      progressively with increasing storage time. Parallel, but smaller, increases in
      IL-1 beta were observed in those units with high IL-8 concentrations. TNF-alpha
      was detected in 3 (10%) of 30 five-day-old PCs, but never exceeded 55 pg per mL
      in any unit tested. IL-6 at levels of 740 and 508 pg per mL was detected in two 5
      day-old units with high white cell counts of 9500 and 14,800 per microL,
      respectively, but not in 21 additional units tested with white cells < or = 9200
      per microL or storage time of < or = 2 days. White cell reduction by third
      generation filters on Day 1 of platelet storage prevented the generation of IL-8
      and IL-1 beta to Day 5 of storage. CONCLUSION: Although IL-8 achieved levels in
      some units of PCs that appear capable of causing physiologic changes, the
      potential adverse effect on transfusion recipients of the infusion of cytokines
      in PCs remains to be investigated.

PMID- 8273125
TI  - Quality control of red cell filtration at the patient's bedside.
AB  - BACKGROUND: Concern has been raised about the quality of white cell (WBC)
      reduction in blood components when it is performed by filtration at the patient's
      bedside. Thus, the quality of red cell (RBC) filtration performed at the bedside
      through two new flatbed WBC-reduction filters was evaluated. STUDY DESIGN AND
      METHODS: In the laboratory, 25 and 10 RBC units suspended in additive solution
      were stored for 1 to 2 and 14 to 21 days, respectively, and filtered through each
      filter. At the end of filtration, an automated complete blood count and a manual
      WBC count (Nageotte chamber) were determined in two samples collected from 1) a
      segment clamped at 5 and 25 cm below the filter along the line connecting
      prefiltration and postfiltration bags and 2) the postfiltration bag. In addition,
      10 of the 11 nurses of the hematology outpatient clinic administered to
      hematologic patients 25 RBC units stored for 1 to 2 days through each type of
      filter. At the end of transfusion, a segment was collected from the transfusion
      set and a WBC count was performed as described above. No filter priming or
      rinsing with saline was done. RESULTS: WBC counts obtained after laboratory
      filtration in the segments were similar to those obtained from the postfiltration
      bags and from the segments collected at the bedside in all cases, with the
      exception of 14- to 21-day-old RBCs filtered in the laboratory through one of the
      filters, which produced slightly higher WBC counts in the segments than were seen
      in the postfiltration bags. The difference was not significant. In no case was
      the count in the postfiltration bag higher than that in the segment. Nurse
      training was easy, and bedside filtration was associated with no untoward
      effects. CONCLUSION: The RBC filtration at the patient's bedside can be equal in
      quality to that performed in the laboratory, at least in such clinical settings
      as hematology and oncology departments in which blood transfusion is common
      practice, and if simple training is provided to the nursing staff. Under the
      conditions of this study, it seems that quality control of RBC bedside filtration
      is feasible and simple.

PMID- 8273126
TI  - Low retention of white cell fragments by polyester fiber white cell-reduction
      platelet filters.
AB  - BACKGROUND: There is intense interest in the potential of current white cell
      (WBC)-reduction filters to prevent the alloimmunization of patients by the
      residual donor WBCs in filtered blood components transfused to them. Little
      attention has been paid to the capacity of current synthetic fiber filters to
      remove WBC membrane fragments bearing detectable leukocyte antigens. STUDY DESIGN
      AND METHODS: Fluorescein isothiocyanate-conjugated monoclonal antibody to a
      universal WBC membrane antigen (CD45) and high-speed centrifugation coupled with
      ficoll-hypaque differential sedimentation were used to quantitate low-density WBC
      fragments in single-donor platelet components before and after filtration to
      determine if a polyester fiber filter retained WBC fragments. RESULTS:
      Prefiltration measurements in 25 single-donor platelet components indicated that
      WBC fragments increased with length of storage up to 5 days at room temperature
      (p < 0.0001). When fragments in eight components were measured before and after
      filtration, absolute values for differences were insignificant (p = 0.15).
      CONCLUSION: WBC fragments were poorly retained by these polyester fiber WBC
      reduction filters. The antigenicity of WBC fragments could contribute to the WBC
      alloimmunization of some recipients of WBC-reduced blood components.

PMID- 8273127
TI  - Evaluation of platelet concentrates stored for 5 days with reduced plasma volume.
AB  - BACKGROUND: Currently, platelet concentrates (PCs) are stored in a suspending
      plasma volume of 45 to 65 mL. Previous studies using second-generation containers
      indicated that PCs stored for 5 days at volumes less than 30 mL have reduced in
      vivo percentage recoveries as compared to PCs stored at volumes of 50 mL or more.
      STUDY DESIGN AND METHODS: This study has evaluated the effect of PC plasma volume
      on the maintenance of in vivo and in vitro platelet properties following 5 days
      of storage, with the purpose of establishing the minimum plasma volume in the
      range of 30 to 50 mL. Twenty paired studies were performed in which identical
      populations of platelets from the same donor (obtained by double manual
      apheresis) were stored in a normal volume (55-60 mL, control) and reduced volume
      (30-50 mL, test) of plasma. Comparison of in vivo viability between test and
      control PCs was performed after random radiolabeling of 1 unit with 51Cr and of
      the other with 111In, with simultaneous transfusion and with calculation of
      percentage recovery and the area below the survival curve (integral) as measures
      of viability. RESULTS: When test unit volumes were > or = 35 mL, essentially
      identical platelet survival curves and in vitro results were obtained for test
      and control. The integral and the percentage recovery for the test units were
      (mean, 95% confidence interval) 98.7 (96.3-101.0) and 99.0 percent (94.7-103.3)
      of those values in the control units, respectively. Test units with volume < or =
      34 mL demonstrated reduced in vivo viability with integral and percentage
      recovery of 81.1 (68.9-93.3) and 80.4 (69.3-91.5), respectively, as compared to
      the control units. This loss was associated with increased metabolic activity
      (lactate production), which may suggest platelet activation due to the increased
      surface-to-PC volume ratio. CONCLUSION: These results show that the storage
      volume of PCs may be reduced from 50 to 60 mL to 35 to 40 mL without any
      significant decrease in in vivo or in vitro platelet quality.

PMID- 8273129
TI  - Auditing into compliance.

PMID- 8273128
TI  - Platelet concentrates stored for 5 days in a reduced volume of plasma maintain
      hemostatic function and viability.
AB  - BACKGROUND: Platelet concentrates prepared from whole blood are generally
      suspended in a standard volume of 50 to 60 mL of plasma and can be stored thus at
      20 to 24 degrees C for up to 5 days. In vitro studies suggested that this plasma
      volume could be reduced to 30 to 35 mL without impairing platelet function. STUDY
      DESIGN AND METHODS: This study evaluated whether platelets stored for 5 days in a
      reduced volume (30-35 mL) of plasma maintained their in vivo viability,
      hemostatic function, and recovery in recipients. Paired autologous platelet
      survival studies were done in 20 adult volunteers to assess platelet viability. A
      rabbit ear bleeding-time model was used to compare the hemostatic effectiveness
      of human platelet concentrates stored for 5 days in the standard or reduced
      volume of plasma. Platelet recovery was compared in thrombocytopenic hospital
      patients. RESULTS: Paired platelet survival studies indicated no significant
      difference between the values in platelet concentrates stored for 5 days in the
      reduced volume of plasma and the values in those stored in the standard volume.
      In the animal model, there was no significant difference in the bleeding times
      achieved by either set of platelet concentrates. The platelet count increments in
      thrombocytopenic patients were measured. The platelet count increments in
      patients who received reduced-volume platelet concentrates were as good as the
      increments achieved in patients given standard-volume concentrates. CONCLUSION:
      The in vivo viability, recovery, and hemostatic function of platelets collected
      in polyvinylchloride plastic containers and stored in 30 to 35 mL of plasma for 5
      days are maintained as well as those of platelets stored in 50 to 60 mL of
      plasma.

PMID- 8273130
TI  - A statistical model for estimating donor postdonation platelet counts after
      plateletpheresis.
AB  - BACKGROUND: To avoid the need, in serial apheresis donors, either to delay
      plateletpheresis until a predonation platelet count is completed or to obtain a
      postdonation count after each procedure, a statistical model has been developed
      to predict the postdonation platelet count from the donor predonation platelet
      count, weight, and hematocrit. STUDY DESIGN AND METHODS: Predonation and
      postdonation platelet counts were measured in two groups of approximately 100
      consecutive donors (Group A to test the model and Group B to validate it), and
      the postdonation counts were calculated with the model. Using stepwise multiple
      linear regression from donor data, estimated postdonation platelet counts were
      found to be comparable to the postdonation platelet counts actually measured.
      RESULTS: Estimated postdonation platelet counts x 10(9) per L (mean +/- SD) for
      each group, respectively, were Group A, 195 +/- 35, versus actual platelet counts
      of 195 +/- 39 (p = 0.43), and Group B, 183 +/- 36, versus actual platelet counts
      of 189 +/- 34 (p = 0.14). Sensitivity and specificity, respectively, were Group
      A, 57 and 99 percent and Group B, 62 and 99 percent. CONCLUSION: For most serial
      apheresis donors, application of this predictor model should preclude the need to
      obtain an extra postdonation platelet count.

PMID- 8273131
TI  - The changing activities of a regional marrow donor program.
AB  - BACKGROUND: A regional marrow donor program was established in 1982. Following
      the establishment of the National Marrow Donor Program (NMDP) in 1987, the
      activities of this regional program changed. STUDY DESIGN AND METHODS: To better
      understand the changes that occurred in the regional marrow donor program, its
      donor recruitment and marrow collection activities through 1991 were studied
      retrospectively. Data analyzed included the total number of potential donors, the
      number and types of potential donors recruited each year, the number of searches
      performed, the number of samples collected for HLA-DR typing and mixed lymphocyte
      culture testing, and the number of transplants in both programs from 1987 through
      1991. Statistical analysis was performed by using chi-square. RESULTS: Initially,
      only persons who donated platelets by apheresis were enrolled into the program.
      In 1986, the regional program's first drive to recruit people who were not
      apheresis donors occurred. The number of such drives increased each year, and in
      1991, 12 drives occurred, which resulted in the recruitment of 1313 potential
      marrow donors. From 1987 to 1991, the number of potential donors in the regional
      program grew from 3252 to 9146, but the proportion of apheresis donors in the
      program decreased. In 1987, 91.9 percent of marrow donors at the regional center
      had been apheresis donors, but in 1991, 41.7 percent had been apheresis donors.
      The number of marrows donated at the regional center increased from 11 in 1987 to
      29 in 1989, but then fell to 24 per year in 1990 and 1991. The decrease in the
      number of donations at the regional program was due to the rapid growth in the
      NMDP file of potential marrow donors and the selection of donors whose HLA
      antigens were more compatible with those of the transplant recipients. In 1989,
      the regional program contained 4.6 percent of all HLA-A,B-typed and 11.2 percent
      of all HLA-A,B,DR-typed potential donors in the NMDP and collected 15.3 percent
      of all marrows. However, in 1991, the regional program contained 2.0 percent of
      HLA-A,B-typed donors and 4.1 percent of HLA-A,B,DR-typed donors and collected 5.3
      percent of marrows. In 1987, 18 percent of the people who donated marrow at the
      regional center were phenotypically HLA-A,B,DR identical with the recipient, but
      in 1991, 92 percent of donor-recipient pairs were phenotypically HLA-A,B,DR
      identical. CONCLUSION: Recruitment activities became an increasingly larger part
      of the Regional Marrow Donor Program's activities. Increasing the size of the
      file of potential donors was necessary to maintain a constant number of
      donations. Persons who were not regular blood donors were an important part of
      the marrow donor program.

PMID- 8273132
TI  - Transfusion and second malignancy.
AB  - BACKGROUND: Perioperative blood transfusion has been reported to cause a variety
      of immunosuppressive effects, including increased rates of malignancy recurrence.
      The effect of perioperative transfusion on second malignancy risk has not
      previously been investigated. STUDY DESIGN AND METHODS: Second malignancy risk
      was evaluated in 1053 patients previously operated upon for colon cancer, and
      these findings are related to perioperative transfusion history. RESULTS:
      Transfusion history did not relate to the probability of a patient's remaining
      free of second malignancy. CONCLUSION: An increased risk of total or second
      malignancies (with the possible exception of lung cancer) was not associated with
      transfusion.

PMID- 8273133
TI  - A phase III trial of recombinant human erythropoietin therapy in nonanemic
      orthopedic patients subjected to aggressive removal of blood for autologous use:
      dose, response, toxicity, and efficacy.
AB  - BACKGROUND: Previous clinical trials have shown that the use of recombinant human
      erythropoietin (EPO) can facilitate autologous blood donation and reduce
      allogeneic blood transfusions in autologous blood donors who are anemic at first
      donation. However, the role of EPO therapy in nonanemic patients remains
      undefined. To identify this role, a randomized, controlled, multicenter dose
      escalation trial was conducted in patients whose initial hematocrit was > 39
      percent (0.39). STUDY DESIGN AND METHODS: EPO (150, 300, or 600 units/kg) or
      placebo was administered intravenously at each of six phlebotomy visits over a 3
      week study period. Sixteen (14%) of 116 patients were unable to complete the
      treatment protocol because of adverse events (n = 11) or for personal reasons (n
      = 5); 2 patients (1 EPO and 1 placebo) experienced serious adverse events.
      RESULTS: In 91 evaluable patients, additional red cell production during the
      study period was 440 +/- 176, 621 +/- 215, 644 +/- 196, and 856 +/- 206 mL (mean
      +/- SD), respectively, for patients receiving placebo and EPO at 150, 300, and
      600 units/kg (p < 0.05 for all EPO groups compared to placebo). However, the
      percentages of patients in each group who received allogeneic blood did not
      differ: 2 (9%) of 23 placebo patients and 6 (9%) of 68 EPO patients. CONCLUSION:
      It is concluded that, while EPO therapy increased preoperative red cell
      production, no clinical benefit could be demonstrated in autologous blood donors
      who were not anemic at first blood donation.

PMID- 8273134
TI  - Reappraisal of optimal hemoglobin standards for female blood donors in Canada.
AB  - BACKGROUND: A hemoglobin (Hb) standard of 115 g per L on the copper sulfate test
      has been in use by the Canadian Red Cross Society Blood Services for female blood
      donor predonation screening since 1989. STUDY DESIGN AND METHODS: To determine if
      this lowered Hb standard results in increased iron deficiency in repeat blood
      donors, a study was conducted to evaluate the performance of the copper sulfate
      test and predonation capillary and venous Hb assays in a population of female
      blood donors most at risk of developing iron deficiency. RESULTS: Of the 174
      donors who were of childbearing age, who were not taking iron supplements, and
      who had made at least three blood donations per year, 45 (25.9%) were iron
      deficient, and 64 (36.8%) had reduced iron stores; only 65 (37.3%) had normal
      iron stores. This study showed that capillary blood is more likely to have a
      higher Hb concentration (3.2 +/- 7.8 g/L) than venous blood samples, which could
      affect the performance of predonation screening assays that are based on
      capillary blood samples at a given discriminating value. With an Hb standard of
      115 g per L, both the copper sulfate and capillary Hb assays were not sensitive
      enough to screen for iron deficiency (sensitivity, 27% and 33%; specificity, 96%
      and 93%, respectively) and were comparable only to the performance of a venous Hb
      assay with a cutoff value of 110 g per L (sensitivity, 27%; specificity, 99%). In
      contrast, an Hb standard of 125 g per L in the copper sulfate test could achieve
      a more optimal sensitivity of 79 percent and specificity of 78 percent.
      CONCLUSION: This study supports the use of a higher Hb cutoff value of 125 g per
      L for female blood donors in the predonation fingerstick copper sulfate test.

PMID- 8273135
TI  - Red cell autoantibody production in utero: a case report.
AB  - BACKGROUND: Autoantibody production by the fetus is thought to be extremely
      unlikely. Only one possible case of in utero autoantibody production against red
      cells by the fetus has previously been described. STUDY DESIGN AND METHODS: A
      case of apparent red cell IgG autoantibody production in utero is reported.
      RESULTS: This was established by a positive direct antiglobulin test in a newborn
      infant without evidence of maternal alloantibodies or autoantibodies. There was
      no evidence of clinically significant hemolysis at the infant's birth. After 6
      weeks, his direct antiglobulin test remained strongly positive. The infant
      thrived without evidence of hemolysis, and after 6 months the direct antiglobulin
      test was negative. CONCLUSION: The production of autoantibodies to red cells in
      utero is possible, though rare. This did not result in apparent hemolysis in this
      patient.

PMID- 8273136
TI  - Controversies in transfusion medicine. Is autologous blood transfusion worth the
      cost? Pro.

PMID- 8273137
TI  - Controversies in transfusion medicine. Is autologous blood transfusion worth the
      cost? Con.

PMID- 8273138
TI  - White cell reduction in blood from donors with sickle cell trait.

PMID- 8273139
TI  - Delayed hemolysis of white cell-reduced red cells.

PMID- 8273140
TI  - Use of white cell-reduced red cells for transfusion through peripheral arterial
      lines.

PMID- 8273141
TI  - Chronic hepatitis C after high-dose intravenous immunoglobulin.

PMID- 8273142
TI  - The risk of overt acute hemolytic transfusion reaction following the use of an
      immediate-spin crossmatch.

PMID- 8273143
TI  - Automated microplate ABO and Rh(D) blood grouping.

PMID- 8273144
TI  - Finishing the cell cycle: control of mitosis and cytokinesis in fission yeast.

PMID- 8273145
TI  - A quick method for immunoscreening recombinant bacterial colonies.

PMID- 8273146
TI  - S-300 gel matrix irreversibly binds single-stranded nucleic acids.

PMID- 8273147
TI  - DNA sequencing by the chemical method: a 10 minute procedure for the G+A
      reaction.

PMID- 8273148
TI  - The Runt domain identifies a new family of heteromeric transcriptional
      regulators.

PMID- 8273149
TI  - Something's fishy here--rethinking cell movements and cell fate in the zebrafish
      embryo.
AB  - A recent paper has challenged the prevailing view that zebrafish blastomeres
      undergo extensive cell mixing and are unrestricted in their cell fates during
      early development. Here, we offer a model that resolves apparent contradictions
      between studies that have examined the origins of cell fate in the zebrafish
      embryo. The model reconsiders cell movements during epiboly, and how cell mixing,
      or the lack of it, can affect the predictability of cell fate.

PMID- 8273150
TI  - Radiation hybrids: irradiation and fusion gene transfer.
AB  - Irradiation and fusion gene transfer can be used to construct detailed genetic
      maps of complex genomes. This technique is complementary to mapping methods based
      on both physical distance and genetic recombination.

PMID- 8273151
TI  - Ethylene gas: it's not just for ripening any more!
AB  - Hormones play a central role in regulating plant growth and development. There
      are five well-characterized plant hormones, the chemically simplest of which is
      the gaseous olefin ethylene. Molecular genetic studies of Arabidopsis are
      beginning to reveal the mechanisms controlling ethylene biosynthesis, perception
      and signal transduction.

PMID- 8273152
TI  - Synthetic enhancement in gene interaction: a genetic tool come of age.
AB  - Synthetic enhancement, in which one mutation exacerbates the severity of another,
      is a genetic interaction of increasing importance in biology. This review focuses
      on the logic of interpreting synthetic enhancement, and begins by comparing the
      phenomenon with genetic suppression.

PMID- 8273153
TI  - Sputum smear negative pulmonary tuberculosis.

PMID- 8273154
TI  - Setting standards for primary health services.

PMID- 8273155
TI  - Onchocerciasis and women's reproductive health: indigenous and biomedical
      concepts.
AB  - Women in a rural farming community in Etteh, Nigeria, have traditional beliefs
      about onchocerciasis which differ from the concepts of modern science.
      Recognizing these beliefs may allow health workers to gain the confidence and
      participation of the people and increase the effectiveness of control programmes.

PMID- 8273156
TI  - Anthropometric classifications: measuring success or failure?

PMID- 8273157
TI  - AIDS education is more than telling people what not to do.

PMID- 8273158
TI  - Pilot study of post operative infections in incisional wounds and split skin
      grafts in a provincial hospital in Zimbabwe.

PMID- 8273159
TI  - Prescribing pattern in acute diarrhoea in three districts in Bangladesh.

PMID- 8273160
TI  - Do ascariasis, trichuriasis and hookworm infections predispose to non-specific
      abdominal symptoms among adults in endemic areas?

PMID- 8273161
TI  - Autokeratoplasty in a developing country.

PMID- 8273162
TI  - Significance of bronchial washings smear negativity in 'suspect' pulmonary
      tuberculosis.
AB  - The role of bronchial washings in patients with 'suspect' pulmonary tuberculosis
      was studied in 55 patients. Bronchial washings increased the diagnostic yield of
      tuberculosis by 28%. It was also able to accurately exclude active tuberculosis
      in 94% patients. Hence it is inferred that absence of acid-fast bacilli in smears
      of bronchial washings is equally important to exclude active tuberculosis.

PMID- 8273163
TI  - Low-cost refractometer for measurement of protein concentration and specific
      gravity of body fluids.

PMID- 8273164
TI  - The hospital water still.

PMID- 8273165
TI  - A simple method of securing a cholangiography cannula.

PMID- 8273166
TI  - Sleeve circumcision.

PMID- 8273167
TI  - Suction drainage with limited facilities.

PMID- 8273168
TI  - Nasogastric tube knotting.

PMID- 8273169
TI  - The use of fishing nylon for surgery in rural areas in north east Zaire.

PMID- 8273170
TI  - Urinary tract isolates in rural Africa.

PMID- 8273171
TI  - Mucoid Pseudomonas aeruginosa in urinary tract infection.

PMID- 8273172
TI  - Is fibroid familial?

PMID- 8273173
TI  - Onchocerciasis is more than skin deep.

PMID- 8273174
TI  - Indigenous African healers promote male circumcision for prevention of sexually
      transmitted diseases.

PMID- 8273175
TI  - Volvulus of the sigmoid colon--a re-appraisal: too soon to abandon Hartmann's
      procedure.

PMID- 8273176
TI  - Fatal tetanus following Stevens-Johnson syndrome.

PMID- 8273177
TI  - Hand-feeding practices among mothers in a semi-urban community in Nigeria.

PMID- 8273178
TI  - Use of sugar in infected wounds.

PMID- 8273179
TI  - Entrapment of the fetal head and symphysectomy.

PMID- 8273180
TI  - Live S haematobium miracidia in the urine of a Zambian boy with bilharziasis.

PMID- 8273181
TI  - Expired reagent strips for haematuria.

PMID- 8273182
TI  - Tuberculous osteomyelitis of zygoma.

PMID- 8273183
TI  - [Contribution of transesophageal echography in auricular and mitral pathology].

PMID- 8273184
TI  - [Carpentier's mitral valvuloplasty. Immediate, early, and long term results. 40
      cases].

PMID- 8273185
TI  - [Chronic aortic insufficiency and left ventricular dysfunction: prognostic value
      of echocardiography].

PMID- 8273186
TI  - [Diagnostic value of pericardial biopsy].

PMID- 8273187
TI  - [3 year outcome of percutaneous endoluminal closure of persistent ductus
      arteriosus. 3 first Tunisian cases].

PMID- 8273188
TI  - [Closure of ductus arteriosus by endoluminal technique. 5 cases].

PMID- 8273189
TI  - [Anatomo-clinical particularities of myocardial infarction in young adults. A
      series of 26 cases].

PMID- 8273191
TI  - [The many-sided symptomatology of Parvovirus infections].

PMID- 8273190
TI  - [Pulmonary restenosis after surgical commissurotomy, treated by percutaneous
      valvuloplasty].

PMID- 8273192
TI  - [Human Parvovirus B19 infection and aplastic crisis].
AB  - Human Parvovirus B19 (B19-virus) is the most frequent cause of aplastic crisis in
      patients with underlying hereditary haemolytic anaemia. B19-virus interrupts
      erythropoiesis by lytic damage of erythroid precursors in the bone marrow.
      Patients with hereditary haemolytic anaemia have a shortened red cell life span
      and a compensatory increased activity of the erythroid precursors in the bone
      marrow. Temporary interruption of erythropoiesis leads to a precipitous fall in
      haematocrit and absence of reticulocytes in the circulation. The symptoms of the
      illness are anaemia and fever. The treatment is red cell transfusion. The
      infection is diagnosed either by direct demonstration of B19-virus-DNA or by
      demonstration of specific IgM-antibodies to B19-virus. The natural infectivity of
      B19-virus is high, and infection is presumably followed by lasting immunity.
      Because the infectivity of cases of aplastic crisis caused by B19-virus is
      especially high, control guidelines are necessary for pregnant seronegative
      staff. A review of the literature is presented.

PMID- 8273193
TI  - [Recurrence problems with preventive primaquine treatment in patients with
      malaria].
AB  - Standard treatment of P. ovale and P. vivax malaria is 1500 mg of chloroquine
      base given over three days followed by 15 mg of primaquine base daily for 14
      days. At the Department of Infectious Diseases, Rigshospitalet, Copenhagen an
      increasing number of cases of relative by primaquine-resistant malaria have been
      observed. The side effects of primaquine are mainly gastrointestinal. Primaquine
      may also cause serious toxic side effects, including methaemoglobin formation and
      haemolytic anaemia, especially in individuals with erythrocyte glucose-6
      phosphate dehydrogenase (G-6-PD) deficiency. We present six patients who
      developed relapses of P. vivax after taking standard doses of primaquine. When
      increasing primaquine dosage, patients must be informed about the possibility of
      more severe side effects.

PMID- 8273194
TI  - [Calcium blood changes in septic conditions. A review].
AB  - Hypocalcemia has been reported in critically ill patients over the last 10-15
      years, however, measurements of Ca2+ in blood have not yet became routine in the
      treatment of severely ill patients. In order to stress the importance of calcium
      in such patients, a review of calcium changes in septic conditions is presented.
      In vitro studies show that the intracellular calcium metabolism is disturbed in
      these patients, and that the changes in extracellular calcium are probably
      secondary to the intracellular changes. Parathyroid hormone secretion is
      inappropriate in septic patients. The reason for this is unknown. Administration
      of calcium parenterally does not seem to affect the prognosis, however calcium
      seems to be beneficial in patients with hypotension. Since the level of Ca2+ in
      blood may have prognostic significance in septic patients, measurements of Ca2+
      in blood should be used routinely in these patients, in order to point out "risk"
      patients as early as possible.

PMID- 8273195
TI  - [Laser therapy of ankle sprain].
AB  - The effect of low-power laser therapy on acute ankle sprains was evaluated in a
      double-blind randomised clinical study consisting of 40 patients from the
      casualty ward. All patients received treatment until their ankle joint was
      painless. No statistically significant differences regarding discolouring, pain,
      oedema, and use of analgetics were observed between patients treated with laser
      and placebo. The patients treated with active laser had a significantly longer
      sick leave.

PMID- 8273196
TI  - [Fetal-pelvic disproportion].
AB  - The files of 186 primiparous women with the diagnosis of fetal-pelvic
      disproportion were studied in order to depict maternal and fetal parameters
      determining the course of delivery. Three groups were compared. One group of
      women who delivered vaginally and two groups, that delivered by caesarean
      section, one with a dilated orifice and one with a non-dilated orifice. The
      maternal age, height and pelvic capaciousness as found by clinical examination
      were registered together with cardiotocography, birth weight, labour
      augmentation, instrumental delivery, fetal presentation, gestation age and the
      conjugata vera (measured at caesarian section). It was found that the maternal
      age and the gestational age were lower in the vaginal delivery group compared to
      the two caesarean section groups. There was no difference between all three
      groups with respect to the other parameters. On this basis it was concluded, that
      it was not possible to identify fetal-pelvic disproportion that would result in
      caesarean section in primiparous women.

PMID- 8273197
TI  - [Foot deformities and relation to the length of leg muscles in Danish children
      aged 3-17 years].
AB  - Seven hundred and sixty-nine children and adolescents from three to seventeen
      years of age, being 98% of the pupils in different classes in seven schools and
      ten kindergartens on Funen, Denmark, were examined in 1991. The Triceps Surae
      muscle was found to be too short, if the corrected foot can only be pressed
      slowly to the right angle. The 1520 footprints showed an increase in the number
      of highly-arched feet through the age groups from 2.3% to 7.3% and a decrease in
      flat-footedness from 41.8% to 5.7%. In the two oldest age groups, 39% of those
      with a high arch, 56% of those with a normal arch and 77% of those with flat feet
      had short calf muscles. We therefore conclude, that it is necessary that a few
      minutes be spent daily in Danish kindergartens and schools on stretching the
      triceps surae.

PMID- 8273198
TI  - [Long-term prognosis of patients with suspected myocardial infarction confirmed
      and not confirmed by diagnosis].
AB  - This study prospectively evaluates the long-term prognosis of patients admitted
      with chest pain under suspicion of acute myocardial infarction (AMI) with and
      without confirmed diagnosis. Altogether 275 patients with and 257 patients
      without confirmed AMI (non-AMI) were consecutively included. During seven years
      of follow-up 122 cardiac events occurred in the AMI patients (i.e. 96 cardiac
      deaths and 26 nonfatal-AMI), and 69, occurred in the non-AMI patients (44 cardiac
      deaths and 25 non-fatal AMI). In multivariate Cox-analysis the following risk
      factors contained independent prognostic information for non-AMI patients: 1) a
      history of angina pectoris and 2) ST or T changes in the ECG on admission. In
      patients with AMI the risk factors were 1) previous AMI and 2) clinical heart
      failure. We conclude that a subset of non-AMI patients who have an increased long
      term risk of cardiac events, can be identified from the medical history and the
      ECG at admission. These patients should be carefully evaluated prior to
      discharge.

PMID- 8273199
TI  - [Serum electrolytes and drug therapy of patients admitted to a geriatric
      department].
AB  - The distributions of sodium and potassium in the serum on admission, and the
      types of medicine used were studied retrospectively in hospitalized geriatric
      patients (n = 1418). Sodium concentrations below 130 mmol/l were found in 7.4%
      and potassium concentrations below 3.0 mmol/l in 5.0% of patients. Risk factors
      for low sodium concentrations were treatment with the combination of
      thiazide+amiloride, potassium-sparing diuretics, thiazides, emergency
      hospitalization and low body weight. Risk factors for low potassium
      concentrations were treatment with the combination of thiazide+amiloride,
      thiazides and female gender. On an average, patients were given two different
      drugs from specified groups both on admission and on discharge, but changes in
      medical treatment were often performed during the hospital stay. Prehospital
      treatment with thiazide diuretics and the combination of thiazide+amiloride was
      frequently withdrawn. 38% were given benzodiazepines on discharge. In 40.4% of
      these, treatment had been started during the hospital stay, most often on account
      of insomnia.

PMID- 8273200
TI  - [Use of psychiatric emergency departments by patients with chronic psychotic
      disorders].
AB  - Ninety chronic psychotic patients' use of a psychiatric emergency ward in
      Copenhagen County was examined. Over a one year period most patients came to the
      emergency ward once or twice when other treatment facilities were not open. They
      came because of an exacerbation of symptoms rather than because of social needs.

PMID- 8273201
TI  - [Occult hereditary spherocytosis in aplastic crisis of unknown cause].
AB  - We describe two cases of aplastic crisis of unknown origin, occurring within one
      week in a 49-year old man and his 20 year old son. They both had undiagnosed
      hereditary spherocytosis, and both of them had earlier had a B19-parvo infection
      without having symptoms of aplastic crisis at the same time. Chronic haemolytic
      anaemia should be considered in adult patients with acute severe anaemia caused
      by aplastic crisis.

PMID- 8273202
TI  - [Migration of a Kirschner wire from hand to elbow. A case report].
AB  - A case of migration of a Kirschner-wire from the hand to the elbow is presented.
      The potential ability of metallic fixing pins to migrate within the patient must
      be recognized, and more frequent postoperative examinations and radiographs
      should be performed after the insertion of such pins to permit earlier detection
      of migration, and thereby to permit earlier removal.

PMID- 8273203
TI  - [Severe consequences of delayed diagnosis and treatment of neurosyphilis].
AB  - A case of full-blown neurosyphilis in a 40 year old university man is
      demonstrated. The disease was initially misdiagnosed as Creutzfeldt-Jakob
      disease. Nuclear magnetic resonance scanning supported this diagnosis. One year
      later the patient was hospitalized owing to increasing neurological deficits. For
      the first time he was examined for syphilis, and the disease was confirmed by a
      WR test. Despite lege artis penicillin treatment the patient was left with severe
      deficits, particularly of the intellect. The old phrase that syphilis can mimic
      any form of psychopathology is still true, and WR is still the test of choice
      whenever a neuropsychiatric diagnosis is unclear.

PMID- 8273204
TI  - [Treatment of apoplexy and an "apoplexy department"].

PMID- 8273205
TI  - [The Alzheimer-apoE4 connection].

PMID- 8273206
TI  - [Estrogen therapy as prevention against coronary disease? It is proved that ...].

PMID- 8273208
TI  - [Asthma in schoolchildren].

PMID- 8273207
TI  - [Mupirocin (Bactroban)--a new antibiotic for local use in bacterial infections].

PMID- 8273209
TI  - [Occurrence of asthma in schoolchildren. Is the disease underdiagnosed?].
AB  - A cross sectional study of 1064 unselected school children aged 6-17 years
      obtained the following for 851 of them (80%): complete data from a questionnaire
      on current asthma diagnosed by a physician, information on previous recurrent
      wheezing and present exposure to tobacco smoking combined with measurement of
      peak expiratory flow rate (PEFR) before and after six minutes running. Seventy
      five (8.8%) had had previous periods of recurrent wheezing, and 535 (62.7%) were
      exposed to tobacco smoking at home. A correlation was found between passive
      smoking and previous recurrent wheezing. Thirty-four (4.0%) suffered from current
      asthma. Thirty-one children (3.6%) without an earlier diagnosis of asthma showed
      a significant exercise-induced fall in PEFR) (at least 15%). Thirty of these 31
      children were followed up, and at reinvestigation, 27 (95%) were confirmed to
      suffer from hyperreactive airways based on significant exercise-induced fall in
      PEFR and/or a significantly increased variability of PEFR of at least 15% as
      measured by home recordings of PEFR. In conclusion the point prevalence of asthma
      diagnosed by a physician was 4.0%. In addition at least 3.2% had reproducible
      significant bronchial hyperreactivity indicating a point prevalence of
      asthma/clinically significant bronchial hyperreactivity of at least 7.2%. Asthma
      seems to be underdiagnosed in school children. Furthermore, our results indicate
      an association between passive smoking and recurrent wheezing.

PMID- 8273210
TI  - [Allergy and bronchial reactivity in children and adolescents from Copenhagen].
AB  - The relationship between bronchial responsiveness and the results of a skin prick
      test was studied in 527 children and adolescents from Copenhagen. All
      participants completed a questionnaire concerning birth weight, breastfeeding,
      month of birth, month of examination, allergic symptoms in themselves or their
      parents. Furthermore, skin prick test reactivity to nine common aero-allergens,
      lung function, serum IgE, and bronchial responsiveness to histamine and exercise
      were measured. A total of 158 (30%) subjects showed signs of allergy (defined as
      a positive reaction to the skin prick test), of whom 53 (10%) subjects had
      positive skin reactivity and 105 subjects had moderate skin reactivity; 366 (70%)
      subjects had no signs of allergic disease as measured by the pride test. The most
      important marker for the degree of bronchial responsiveness was asthma (p <
      0.001), month of examination (p < 0.01) and allergy (skin reactivity to one or
      more allergens) (p < 0.05). Furthermore, the degree of bronchial responsiveness
      to inhaled histamine was significantly related to a history of asthma in two
      first degree relatives (p < 0.01) and the skin reactivity to house-dust mites (p
      < 0.01), whereas the degree of bronchial responsiveness to exercise was
      significantly associated with the level of serum IgE (p < 0.05), month of birth
      (p < 0.001) and birth weight (p < 0.05). In conclusion, allergy is an important
      risk factor for the presence of increased degree of bronchial responsiveness to
      inhaled histamine and to exercise.

PMID- 8273211
TI  - [Increasing asthma mortality in Denmark 1969-1988. Not because of changed coding
      practices].
AB  - We have studied asthma mortality in Denmark from 1969 to 1988. Age standardized
      mortality rates calculated in three age groups, 10-34, 35-59, and > 60 years,
      disclosed similar trends. Increasing mortality from asthma in the mid-1970s to
      1988 was seen in all three age groups with higher mortality in 1979-1988 as
      compared with 1969-1978 of 95%, 55%, and 69%, respectively. Since the eighth
      revision of the International Classification of Diseases (ICD-8) was used in
      Denmark over the entire 20-year period, changes in coding practice due to change
      of classification system cannot explain the findings.

PMID- 8273212
TI  - [Transesophageal echocardiography for registration of hemodynamics. A new tool in
      anesthesiology].
AB  - During the last ten years, transesophageal echocardiography has become an
      important tool for cardiac monitoring. In other countries it is widely applied,
      especially in cardiac surgery, but the areas of application are still expanding.
      Transesophageal echocardiography is a non-invasive technique in contrast to most
      other methods available for monitoring central haemodynamics. The complication
      frequency is extremely low. However, correct therapeutic decisions depend on
      profound experience with the equipment and image interpretation. The scope of
      transoesophageal echocardiography as a new tool in haemodynamic monitoring is
      described in this paper together with preliminary results.

PMID- 8273213
TI  - [Calcium signals in blood cells].
AB  - Stimulation of blood cells by binding of agonists to receptors initiates cellular
      calcium signals. The signals appear as transient increases of the cytosolic
      concentration of ionized calcium. The signals influence secretion, adhesion,
      phagocytosis, movements and proliferation of the blood cells. The calcium signals
      are controlled by other signalling systems that regulate calcium transporting
      devices located in the plasma membrane and the membranes that surround the
      cellular calcium stores. Calcium ions are transported through channels, pumps, or
      exchangers located in the cellular membranes. Several calcium transporters are
      subjected to cellular feedback mechanisms. A few pathological disorders of the
      calcium signal system are known.

PMID- 8273214
TI  - [Anal ultrasonography in anal incontinence].
AB  - Endosonography gives detailed information on the internal and external anal
      sphincters. The goals of this study were to evaluate findings on anal
      endosonography in patients with anal incontinence and to study the value of
      endosonography for selecting the most effective surgical treatment. Forty-eight
      patients with incontinence for either gas (17 patients) or faeces (31 patients)
      were studied. Nineteen patients had idiopathic incontinence, 29 were incontinent
      due to previous obstetrical or surgical trauma. Endosonography and measurement of
      anal canal pressures were performed in all patients, 40 had needle
      electromyography. The endosonograms were evaluated without knowledge of the
      clinical findings and correlated with the results of needle electromyography,
      with the anal pressures, and to the type of surgery subsequently performed. In 30
      patients surgery was subsequently planned on the basis of the results of
      endosonography and the anophysiologic examinations. Endosonograms showed defects
      in 27 external sphincters, 12 of whom had internal sphincter defects also. One
      patient had an abnormal thinning of the external sphincter. Eight patients had
      defects of the internal sphincter as the only finding. Twenty-two of the patients
      with sonographically detected defects or thinning of the external sphincter had
      an EMG performed, this showed defects of the external sphincter in 18, four
      defects in the middle and upper anal canal had not been found. There was no
      correlation between the sphincteric defects found by endosonography and the anal
      canal pressures. Sphincter reconstruction was offered to most patients with
      damage to the external sphincter; patients with isolated defects in the internal
      sphincter or intact internal and external sphincters were offered a number of
      other surgical procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273215
TI  - [Intraoperative autotransfusion. Reinfusion of erythrocytes in total hip
      arthroplasty reduces the need for blood from banks].
AB  - We have tested a cell-saver system, which collects, washes, concentrates and
      filtrates red blood cells before autotransfusion. The study consisted of 35
      consecutive patients who had a total hip arthroplasty (THA), 18 using the cell
      saver and 17 not using it. There was no significant difference in the
      peroperative bleeding, or in the total blood loss. The median blood loss was 1950
      ml (925-6337 ml) in the cell-saver group and 2350 ml (1260-4440 ml) in the
      control group. The need for homologous transfusion was significantly higher in
      the control group compared to the cell-saver group, median 500 vs 250 ml of sag-M
      blood. This difference is of the same magnitude as the amount of autotransfused
      red blood cells suspended in saline water, median 398 ml. In the cell-saver group
      nine patients did not need any homologous transfusions at all, whereas in the
      control group only one did not need any transfusion.

PMID- 8273216
TI  - [Acupuncture treatment of knee arthrosis. A long-term study].
AB  - The purpose of this study was to examine acupuncture treatment of patients with
      osteoarthrosis of the knee. Twenty-nine patients with a total of 42
      osteoarthritic knees were randomized to two groups. Group A was treated while
      group B served as a no treatment control group for nine weeks. Analgesic
      consumption, pain and objective measurements were registered. In the second part
      of the study 17 patients (26 knees) continued with treatments once a months.
      Registrations were continued for a total study period of 49 weeks. Comparing
      group A with B, there was a significant reduction in pain, analgesic consumption
      and in most objective measures. In group A + B combined there was an 80%
      subjective improvement, and a significantly increased range of movement of the
      knee. Results were significantly better in those who had not been ill for a long
      time. The second part of the study showed that it was possible to maintain the
      improvements.

PMID- 8273217
TI  - [Detection of morphine after ingestion of poppy seeds].
AB  - The aim of this study was to investigate whether morphine can be detected in
      urine after the ingestion of poppy seeds bought in Denmark. Morphine and codeine
      were determined in 10 different poppy seed specimens bought in Denmark. Ten and
      25 g of the specimens containing the highest amount of morphine and codeine were
      consumed by respectively six and seven volunteers. Urine samples were collected
      for analysis at intervals up to 24 h. All samples were found positive by
      radioimmunoassay up to 24 h after ingestion. Using the less sensitive thin layer
      chromatography method, one of six and two of seven were positive, two to four
      hours after intake of respectively 10 and 25 g of the specimens. We conclude that
      the detection of morphine in urine does not necessarily indicate an illegal drug
      use.

PMID- 8273218
TI  - [Amiodarone-induced skin pigmentation].
AB  - Amiodarone (Cordarone) is used in the treatment of cardiac arrhythmias. A blue
      grey skin pigmentation appears after long term use or a high concentration of
      amiodarone. Two cases are described. Histopathological findings of skin punch
      biopsies from the face showed collections of yellow-brown granula pigment within
      histiocytes throughout the dermis. Sunlight initiates accumulation of the
      pigment. It is recommended to use sunprotection to avoid the pigmentation.

PMID- 8273220
TI  - [Effective prevention of recurrent duodenal ulcer with supplementary antibiotic
      therapy].

PMID- 8273219
TI  - [Seminal vesicle cyst accompanied by unilateral hydronephrosis].
AB  - Seminal vesicle cysts are uncommon. Most often they are benign unilateral and
      associated with anomalies of the ipsilateral kidney. The clinical picture is
      characterized by a retrovesical cystic tumor which may be asymptomatic or cause
      nonspecific symptoms. A case report of most probably bilateral occurrence of
      seminal vesicle cysts accompanied by unilateral hydronephrosis is presented.

PMID- 8273221
TI  - [Hearing loss and spinal anesthesia].

PMID- 8273222
TI  - [The aspect of gender--once again].

PMID- 8273223
TI  - [The intraprostatic spiral. Long-term results in 150 consecutive patients].
AB  - The clinical results of treatment of infravesical prostatic obstruction with an
      intraurethral coil in 150 consecutive patients are reported (previously published
      in (7)). The median follow-up time was 8.6 months (range 0 to 60 months). In 89
      patients the spiral was removed after an average of four months (range 0 to 50
      months); on account of dysfunction of the spiral in 58 cases, planned
      prostatectomy in 17 cases and unrelated to the spiral (stroke etc.) in 14 cases.
      A total of 34 patients died with the coil in situ. Approximately two-thirds of
      the patients had no or few voiding symptoms, while one fourth had moderate
      symptoms, leaving only approximately 10% with severe prostatism. Chronic
      bacteriuria was noted in 51 patients but was not a clinical problem. Migration
      occurred 65 times in 47 patients but this only led to coil removal in eight.
      Calcification of the coil was noted mainly after long-term treatment and we
      recommend replacement of the coil after two years. We conclude that the
      intraprostatic spiral is a useful alternative to an indwelling catheter. Life
      long follow-up is, however, necessary in most patients.

PMID- 8273224
TI  - [Hormone replacement therapy and risk of ischemic heart disease and other causes
      of death. A review of studies published 1970-1992].

PMID- 8273225
TI  - [Is it possible to live with clean intermittent catheterization?].
AB  - In the period 1983 to 1992, 208 patients with bladder dysfunction were introduced
      to clean intermittent self-catheterization. Through questionnaires and
      retrospective study of patient records we found that 57% of the patients were
      very satisfied with this treatment modality. Seventy percent found it easy to
      learn to catheterize themselves and 39% experienced improval of everyday life.
      Thirty-five percent never had bacteriuria. No serious complications were seen.
      Conclusively we found that clean intermittent self-catheterization is a good
      treatment modality for patients with bladder dysfunction. It is easy to learn,
      easy to perform and is very well accepted by the patients.

PMID- 8273226
TI  - [Preoperative or postoperative local anesthesia. Effect on postoperative pain
      treatment].
AB  - A randomized, double-blind trial was conducted to compare the efficacy of
      preincisional and postincisional wound infiltration with 1% lidocaine (40 ml) on
      postoperative pain. Thirty-seven patients scheduled for elective inguinal
      herniotomy participated. The demand for additional postoperative analgesics
      occurred earlier in those who received lidocaine infiltration after incision (165
      min) than in those who received preincisional lidocaine (225 min), p < 0.05). The
      preincisional lidocaine infiltration group also had fewer patients requiring
      supplemental analgesics (58%) than the postincisional group (94%) (p < 0.05). We
      conclude that preincisional infiltration of the surgical wound with lidocaine is
      a more effective method for postoperative analgesia than postincisional
      infiltration.

PMID- 8273227
TI  - [Giardiasis in children with chronic diarrhea. Incidence, growth, clinical
      symptoms and changes in the small intestine].
AB  - During a six-year period, 29 children (aged 0.7-13.5 years, mean 3.3 years)
      suffering from chronic diarrhoea due to giardiasis were studied. The incidence of
      this illness was 81 per 1,000,000 per year among children aged 0- < 7 years.
      According to growth charts, relative height and weight of the patients decreased
      significantly (both approximately 0.5 SD) from before the onset of diarrhoea to
      the time of diagnosis and subsequently increased up to the end of catch-up
      growth. Small intestinal mucosal specimens were studied. Two patients had severe
      villous atrophy, 8 moderate abnormalities, 6 only slight changes and 13 biopsies
      were normal. D-xylose or lactose malabsorption was detected in 25% of the
      patients. The lactose malabsorption was due to hereditary low lactase levels.
      None of the patients with a Danish ethnic background showed lactose
      malabsorption. D-xylose absorption and the relative weight loss of the patients
      correlated with the degree of mucosal damage. Patients with persistent diarrhoea
      (n = 19) were younger and had a shorter duration of diarrhoeal illness and a more
      significant weight reduction than those with intermittent diarrhoea (n = 10).
      However, the age at onset of symptoms was similar in the two groups (medians 1.3
      years). Seven patients contracted the disease abroad. They all developed
      persistent diarrhoea and had a more severe course of the illness than those who
      acquired the disease in Denmark.

PMID- 8273228
TI  - [The Sundholm infirmary. Management of disorders in individuals admitted to an
      institution for homeless persons].
AB  - The aim of this retrospective study was to describe diseases seen and treated at
      the infirmary at Sundholm, an institution for homeless people. In 1991 there were
      124 admissions to the department. The problems treated were in 47 (37.9%) cases
      mainly related to alcohol abuse, in 26 (21%) cases medical or surgical diseases,
      in 12 (9.7%) drug abuse problems, in 10 (8.1%) psychoses and in five (4.0%)
      problems following crisis or trauma. In 24 (19.4%) admissions the health problems
      were due to various combinations of physical and psychiatric diseases and could
      not be classified further. In 96% of the admissions the patient was diagnosed as
      having one or more diagnosis concerning alcohol or drug abuse or major
      psychiatric disease. The infirmaries at the welfare homes in Denmark are a
      specialized alternative to more traditional treatment for the homeless.

PMID- 8273229
TI  - [Use of restraints in a psychiatric department, Frederiksberg Hospital, before
      and after introduction of the new psychiatric law. Restraining devices].
AB  - The purpose of this investigation was to register if the new Danish law
      concerning commitment and compulsory procedures in psychiatry from 1.10.1989
      caused changes in the use of restraints. During the period 1.2.1988-30.9.1991 all
      compulsory procedures in the Department of Psychiatry, Frederiksberg Hospital,
      were registered. A total of 145 patients were restrained during 167 admissions.
      No changes were registered in the number of restraints in connection with the law
      reform, but the duration of the fixations increased by 42%. The number of
      medications given forcibly in connection with the restraints increased
      significantly. One of the purposes of the the law reform was to reduce the number
      and duration of restraints. This purpose has not been fulfilled.

PMID- 8273230
TI  - [Acute suppurative thyroiditis].
AB  - A woman aged 54 years with acute suppurative thyroiditis is described. The
      patient had a well-known non-toxic diffuse goitre with a cyst in the left lobe.
      She was treated with levothyroxine (Eltroxin) for three years before actual
      hospitalization. Four weeks previously she had been treated with sulphamethizole
      for a bladder infection. Antibiotic treatment, surgical drainage and, finally,
      lobectomy of the left thyroid lobe cured the patient, including regression of
      paraesthesia in the left arm. E. coli was found in urine, blood and pus bonum
      from the abscess.

PMID- 8273231
TI  - [Average life expectancy and mortality in Denmark].

PMID- 8273232
TI  - [Does vasectomy increase the risk of prostatic cancer?].

PMID- 8273233
TI  - [Neonatal survival of very low birth weight infants].

PMID- 8273234
TI  - [Nitrosamine formation via non-prescription drugs?].

PMID- 8273235
TI  - [Microalbuminuria--a pawn in several games].

PMID- 8273236
TI  - [Microalbuminuria--a valuable diagnostic parameter].
AB  - The concept of microalbuminuria is reviewed. Measuring the urinary albumin
      excretion rate and testing for microalbuminuria is well established in the
      control and treatment of patients with insulin-dependent diabetes mellitus.
      Microalbuminuria predicts nephropathy and early cardiovascular death. In the
      presence of microalbuminuria, frequent examinations are warranted for early
      detection of retinopathy, hypertension and for optimizing the glycaemic control.
      In patients with non-insulin dependent diabetes, the independent value of
      microalbuminuria as a cardiovascular risk factor is not yet clarified. The
      urinary albumin excretion rate should be measured at diagnosis, because the
      indications are that presence of microalbuminuria reinforces the urge to
      intervene against other well-documented cardiovascular risk-factors
      (hypertension, dyslipidemia, tobacco and obesity). In the non-diabetic population
      there is accumulating evidence that an elevated urinary albumin excretion rate is
      associated with early cardiovascular morbidity and mortality. Large scale cross
      sectional and prospective studies are needed in order to further clarify the role
      of microalbuminuria as an independent risk factor in the background population.

PMID- 8273237
TI  - [Screening of microalbuminuria with the Micral-Test. A semi-quantitative urinary
      dipstick].
AB  - Microalbuminuria, defined as a urinary albumin excretion rate of 20-200
      micrograms/min, predicts diabetic nephropathy and cardiovascular disease in
      diabetic patients. An increased urinary albumin excretion rate is probably also
      associated with cardiovascular disease in non-diabetic subjects. Thus, screening
      for microalbuminuria is of major importance. A semi-quantitative urinary dipstick
      method, Micral-Test, has been developed for this purpose. In a urine sample
      collected overnight from each of 1359 subjects the Micral-Test was evaluated with
      a quantitative ELISA-method as the standard. Sensitivity, specificity and
      diagnostic specificity in detecting microalbuminuria was 92, 58 and 12%
      respectively. The prevalence of microalbuminuria was 5.6%. In conclusion, the
      Micral-Test is highly sensitive in detecting microalbuminuria, but at the expense
      of a relatively high number of false positive tests.

PMID- 8273238
TI  - [Interphase cytogenetics--a new technique for analysis of acquired genetic
      changes in tumor cells].
AB  - Newer genetic investigations of solid tumours by means of in situ hybridization
      (ISH) is reviewed. In situ hybridization, ISH, is a relatively new molecular
      biological method which can be used as a supplement to analysis of chromosome
      aberrations in tumour cells. Labelled DNA or RNA sequences (probes) are bound to
      specific sequences on cell chromosomes. After hybridization, the complementary
      sequences of the probe can be visualized and observed in a microscope. In
      contrast to classical cytogenetics where the chromosomes are studied in the
      mitosis, ISH can also be carried out on non-mitotic cells. The term "interphase
      cytogenetics" refers to this application of ISH, which can demonstrate the
      distribution of cells with different genotype without previous cell culturing.
      Interphase cytogenetics has been used for the analysis of several different
      tumour types where it gives fast and reliable information about specific
      cytogenetic aberrations in tumour cells. It is to be anticipated that this
      laboratory technique will be employed increasingly in the diagnosis and follow-up
      of certain malignancies.

PMID- 8273239
TI  - [Patient satisfaction--a study of patients' assessment of the treatment at a
      department of orthopedic surgery].
AB  - A study among day-case and inpatients on an orthopaedic ward has been carried out
      to assess patient satisfaction. A single-page questionnaire were mailed to 445
      patients, 388 (87.2%) returned the questionnaire. Three hundred and fifty five
      (79.8%) answers were usable. We found an overall rate of satisfaction with the
      given treatment of 71.3%, 20.3% were dissatisfied. We found the group of day-case
      patients more satisfied than the group of inpatients. The group of patients who
      underwent arthroscopic surgery were identified as being the most dissatisfied.
      There were among all patients a large group who were dissatisfied with the amount
      of perioperative information and especially the amount of postoperative out
      patient control. We recommend a higher degree of written information including
      information about risk of complications and failures.

PMID- 8273240
TI  - [Analgesic effect of low-dose intra-articular morphine after ambulatory knee
      arthroscopy].
AB  - The purpose of this study was to demonstrate the effect of intra-articular
      morphine following knee arthroscopy performed in infiltration analgesia. Fifty
      two healthy patients were randomized to receive either morphine 1 mg or placebo.
      The pain was assessed two, five, eight and 24 hours after the procedure by 1) a
      VAS scale and 2) the amount of acetaminophen consumed. Demographic data in the
      two groups were similar. The pain scores at eight and 24 hours and the
      acetaminophen consumption after eight hours were lower in the morphine group (p <
      0.05). Our results confirm the hypothesis of peripherally distributed opioid
      receptors. Stratifying data in therapeutic vs. diagnostic arthroscopy suggests an
      additional effect of morphine in patients undergoing therapy (0.05 < p < 0.10),
      an aspect which supports the hypothesis of peripherally administered morphine
      acting as a potential suppressor of the substance P mediated cytokine cascade.
      Intraarticular morphine 1 mg after knee arthroscopy offers efficient analgesia
      lasting more than 24 hours. The method is devoid of side effects and deserves
      wider recognition.

PMID- 8273241
TI  - [Analgesic effect of 2 different doses of intra-articular morphine after
      ambulatory knee arthroscopy. A randomized, prospective, double-blind study].
AB  - The effect of intra-articular morphine following knee arthroscopy has been
      verified in several studies, but the optimal dose has not been established. An
      earlier study by the authors showed significant effect of one mg morphine versus
      placebo. In this study, fifty patients were randomized to receive either two or
      four mg of intra-articular morphine following day-case knee arthroscopy in
      infiltration analgesia. The injected volume in both groups was five ml. The pain
      was assessed preoperatively, two, four, eight, 24, 36 and 48 hours after the
      procedure by 1) a VAS scale and 2) amount of acetaminophen consumed. Forty-seven
      patients completed the study. Demographic data in the two groups were similar.
      The results showed no significant difference in VAS score between the two dose
      regimes at any time. Onset of pain after cessation of the local analgesia was not
      influenced by the morphine dose. On this basis it is recommended to limit the
      dose of intraarticular morphine, as local adverse reactions to morphine cannot be
      ruled out.

PMID- 8273242
TI  - [Relevance of cultures for the antibiotic treatment in acute perforated
      appendicitis].
AB  - The case records of 71 patients (31 women and 40 men aged 5-76 years, median age
      18) who were registered under the diagnosis of perforated acute appendicitis at
      the Department of Surgery, Frederikssund Hospital between 1 January 1983 to 31
      December 1988 have been reviewed in order to examine the relevance of culturing
      peritoneal swabs for the antibiotic treatment given. Four antibiotic regimens
      were used. In 65% of the cases, the cultured bacteria were completely sensitive
      to gentamycin and metronidazole (82% when cultures where there was no growth are
      included), the corresponding figure for the treatment given was 48% (65%). Thirty
      one percent developed postoperative infections, 20% in the form of abscesses. In
      four percent of the cases where bacterial resistance to the given antibiotic
      treatment was found did this result have a consequence in relation to further
      treatment. The result of culture was on average available 2.1 days after
      antibiotic treatment had been terminated. The cultures could have greater
      relevance if 1) the results were communicated to the ward within one to two days
      2) bacterial type and pattern of antibiotic sensitivity were registered in such a
      manner that the effectivity of the standard antibiotic regime could be controlled
      and 3) if demonstration of possible exogenous contamination were used as a
      parameter in the department's quality control.

PMID- 8273243
TI  - [Benign cerebral gliomas. Clinical and radiological characteristics].
AB  - Between July 1988 and July 1990, 42 patients with low-grade gliomas of the
      cerebrum were treated in our department. Their age ranged from six to 72, there
      were 27 males and 15 females. Seventy-nine percent of the patients had suffered
      from epileptic fits, in 69% it was the presenting symptom. Thirty-one percent had
      normal neurological examination. On CT-scanning most tumours were hypodense, one
      third demonstrated enhancement after intravenous contrast. Midline shift
      suggested a grade two tumour, but otherwise it was not possible to distinguish
      between grade one and grade two tumours on CT or MR. There was an unaccountable
      overweight of tumours on the left side of the brain. Forty patients underwent
      surgery, in one-third a radical extirpation was undertaken. In six patients a
      biopsy was nondiagnostic. Twenty-five percent had postoperative radiation. Adult
      patients who suffer an epileptic seizure without any other obvious aetiology
      should have a CT or MR scan even in cases when the neurological examination is
      normal.

PMID- 8273244
TI  - [Chronic radiation enteropathy. A retrospective study].
AB  - In the period 1968-1989 50 patients, 38 women and 12 men, aged 30-76 years,
      median 58 years, were referred to the Department of Gastroenterology,
      Rigshospitalet for severe chronic radiation enteropathy. Most women had received
      radiation for gynaecological cancer, and most men for urogenital cancer. The
      initial symptoms of the enteropathy were diarrhoea in 74%, abdominal pain in 62%
      and weight loss in 52%. Twelve per cent had visible blood in the stools. Ten per
      cent had fistulas. The symptoms occurred 0-37 years, median ten months after the
      radiation. The radiation enteropathy had necessitated one or more laparotomies in
      35 patients, most often because of subileus/ileus, including resection of the
      small bowel or the colon in 25 patients, and establishment of an ileostomy or a
      colostomy in 11. Seven patients developed new fistulas postoperatively. In 32
      patients one or more tests for malabsorption were performed as a guidance for
      therapy: stool mass (26 patients), faecal fat excretion (26 patients), Schilling
      test (22 patients), lactose absorption (11 patients) and bile acid breath test
      (seven patients). Half of the patients had diarrhoea, including one third of the
      patients without intestinal resection. Two thirds had steatorrhoea, including
      half of the patients without small bowel resection. Three fourths showed
      decreased absorption of vitamin B12, including half of the patients without ileal
      resection. All patients studied had abnormal deconjugation of bile acids and more
      than half of them had bile acid malabsorption. Malabsorption of lactose was found
      in only one patient. There was no correlation between the radiological and
      functional abnormalities of the small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273245
TI  - [Local treatment of non-suppurative otitis externa. A double-blind randomized
      study].
AB  - A comparison between a plain steroid lotion and a steroid lotion with an
      additional keratolytic and antiseptic was conducted in order to assess the value,
      if any, of additives in the treatment of dry external otitis. Sixty patients with
      dry external otitis were treated with either a plain steroid lotion or a steroid
      lotion with additives. Assessments were made prior to and after one week of
      treatment regarding erythema, oedema, secretion, itching, pain and spontaneously
      reported side-effects. No significant differences in efficacy were observed
      between the treatments. Statistically significant differences in favour of the
      plain steroid lotion were found with regard to reduction of erythema and
      occurrence of spontaneously reported side-effects. These findings invalidate the
      demands of additives to steroid lotions in the treatment of dry external otitis.

PMID- 8273246
TI  - [Hydrogen sulfide poisoning in a farmer].
AB  - A case of hydrogen sulfide intoxication in a farmer is described. He collapsed in
      a mobile tank, recently used for spreading manure and was comatose on arrival at
      the hospital. He survived, but still suffers from a toxic/anoxic psychosyndrome.
      On site measurements showed high concentrations of hydrogen sulfide. The
      treatment is controversial and is discussed.

PMID- 8273248
TI  - [Economical laboratories].

PMID- 8273247
TI  - [Firework burns: effect of prevention].

PMID- 8273249
TI  - [Increasing blood pressure and development of microalbuminuria in type I diabetes
      mellitus--which one comes first?].

PMID- 8273250
TI  - [Aminoglycoside single or multiple daily doses?].

PMID- 8273251
TI  - [Significance of the sedative zolpidem in combination with alcohol and
      benzodiazepines in patients with physical dependence].

PMID- 8273252
TI  - [Withdrawal psychosis and zolpidem].

PMID- 8273253
TI  - [Blood transfusion and risk of surgical infection].

PMID- 8273254
TI  - [Effect of synthetic hydroxyapatite ceramics on long-term cultures of isolated
      chondrocytes].
AB  - This study deals with the influence of hydroxyapatite-ceramic on long-term
      cultures of rabbit articular chondrocytes. By additioni of granules of this
      material into the culture wells improval of cell proliferation by factor 12 over
      a period of twelve weeks is found. More important is the maintaining of the
      status of differentiation of the chondrocytes, documented by immunoidentification
      of the expressed collagen I production over collagen II as marker for
      chondrocytes. In controls without addition of hydroxyapatite-ceramic there is a
      dynamic increase of collagen I production over the culture period and
      morphological alteration of the cell shape leading to fibroblast-like cells. As
      this dedifferentiation is the main problem concerning chondrocytes long-term
      cultures, the addition of HAC into the culture medium is a simple and effective
      method enhancing the productivity of the culture system. Moreover this
      experimental design with chondrocytes as cells familiar with mineralized matrix
      gives an important proof of the excellent cytocompatibility of the hydroxyapatite
      ceramic used in this study.

PMID- 8273255
TI  - [The value of closed reduction of fractures of the lower thoracic and lumbar
      spine and computerized tomography follow-up].
AB  - The objectives of this prospective study were to investigate the value of the
      immediate closed reduction following fractures of the thoracolumbar and lumbar
      region. To reach that goal we performed a two stage CAT scan procedure before and
      after the reduction maneuver in a distinct patient population. The aim was not
      only to investigate the biomechanical process but also to evaluate and describe
      certain fracture types which have a good prognosis due to closed reduction
      according to posttraumatic spinal stenosis because of protruding posterior wall
      fragments and those who fail, respectively.

PMID- 8273256
TI  - [Reconstructive surgery of knee para-articular amputation stumps].
AB  - Reconstructive plastic procedures in primary care and in postprimary/secondary
      treatment following below knee and above knee amputation are discussed. Short
      amputation stumps and stumps suffering from insufficient soft tissue coverage
      should be primarily avoided employing salvage replantation techniques.
      Secondarily conventional flaps and grafts, tissue expansion and/or microsurgical
      free tissue transfer all serve for achieving stable skin conditions and preserve
      adequate stump lengths. Interdisciplinary treatment racionale will lead to
      improvement of functional and social rehabilitation.

PMID- 8273257
TI  - [Tibial intramedullary nailing without open drilling].
AB  - By means on the basis of a prospective study of 33 osteosynthesis with the
      unreamed tibia nail (UTN) the following conclusions were found: 1. A technical
      simple, intramedullary solid strength bearing device in only two diameters is
      available, therefore costs for stock keeping are low. Systematic interlocking of
      the nail is necessary. Regarding the multiplicity of indication as well as the
      mechanical character the UTN is close to the principle of the internal fixator.
      2. As a result of its solid constitution remarkable hollow cavities do not exist,
      so that retention of hematoma or secretions is limited (prophylaxis of
      infection). 3. In case of a closed nailing procedure the less rigid fracture
      fixation is favourable for the biology of the bone healing (fracture hematoma,
      less traumatic procedure without reaming of the medullary cavity, etc.). 4. The
      frequently observed breakage of interlocking bolts leads spontaneously to a
      dynamisation favourable as to time and therefore to a better bone healing process
      (callus formation). 5. Time intervals of bony fractures consolidation are
      significantly shorter compared to the exclusive osteosynthesis with the external
      fixator [3]. 6. The unreamed tibia nail is an implant for both primary
      stabilisation of closed diaphyseal fractures of the tibia with soft tissue injury
      and for secondary procedure/treatment for example after external fixator
      osteosynthesis or initial non-operative treatment. Early change of procedure
      seems to be of importance.

PMID- 8273258
TI  - [Surgical intensive care of the elderly].
AB  - Intensive care treatment of elderly patients is discussed controversially.
      Especially the success of maximal therapeutic efforts is questioned in this
      group. Therefore, this paper analyses prospective data of 1572 patients of a
      surgical intensive care unit with respect to age-related outcome. Besides the
      anticipated high proportion of concomitant diseases and an associated increased
      mortality of aged patients, there are no specific age-dependent differences. Old
      patients benefit from maximal therapeutic efforts to the same extent like younger
      patients. The authors conclude from the data that the patient's age per se should
      not influence the indication for intensive therapeutic interventions.

PMID- 8273259
TI  - [Valgisation osteotomy of unstable pertrochanteric femoral fracture. Results of
      92 patients over 7.75 years].
AB  - We report on 92 patients (average age: 76.9 years) with unstable trochanteric
      fractures (Type A2 and subtypes according to the AO/ASIF-Classification) that
      were treated by valgisation/medial displacement osteotomy and 130 degrees-angled
      blade plate fixation during a time period of 7.75 years at the Department of
      Traumatology of the University Clinics of Frankfurt. Average time in the OR was
      106 min, average amount of blood necessary was three units. The rate of
      complications due to the implant was 14.1% taking into account: "cut out" of
      blade (four patients), loosening of plate (three patients), failure of implant
      breakage (two patients)--and development of delayed union (2 patients). There
      were 4.3% hematomas and 3.3% infections that required revisional surgery. 16
      (17.4%) out of 92 patients died during their hospital stay. 77.2% of surviving
      patients regained walking ability during their hospitalization and only 12% had
      to be dismissed to a nursing home. "Pros and cons" of our method of treatment for
      these fracture types against DHS and gamma-nailing are discussed.

PMID- 8273260
TI  - [Amputation injuries of the upper extremity--early complications after
      replantation and revascularization].
AB  - Within a time of ten years 144 patients with difficult injuries on their hands
      were operated. These were 95 replantations and 102 revascularizations. 26
      patients had to be operated again because of arterial and venous thrombosis. 46%
      of our patients had early vascular complications already within 24 hours. The
      frequency of thrombosis was increasing with the accompanying soft tissue injury
      and therefore with the gravity of the trauma. Avulsion injuries had of course the
      worst prognosis. After diagnosis of vascular occlusion within the replanted
      finger there should be a quick surgical revision of the anastomosis. With the
      help of application of urokinase into the artery we could create the circulation
      without any new production of the anastomosis in two cases. With a subtile
      technique of the disposition of the anastomosis and two venous connections to one
      artery with the replanted fingers we could reduce the rate of thrombosis and
      improve the results.

PMID- 8273261
TI  - [Effects of flexed position of the wrist joint after flexor tendon sutures on the
      median nerve].
AB  - Twelve patients with dynamically treated ruptures of finger flexor tendons the
      median nerve was electroneurologically examined at an average of 16 months after
      operation. The parameters were abnormal in about one third to three quarters of
      the patients. In accordance with literature the reason for this is seen in
      pronounced flexion position of the wrist during treatment according to Kleinert.

PMID- 8273262
TI  - [Malleolar fractures with ankle joint instability--experience with the
      positioning screw].
AB  - Malleolar fractures with an unstable ankle joint require additional
      stabilization. Different implants exist: We present the results of 135/155
      patients treated with the so-called positioning screw. In 123 patients the
      positioning screw showed a spontaneous loosening with functional treatment and
      was therefore removed with the rest of the implants after eight to twelve months.
      In twelve cases the screw was broken. In 3/21 patients with the old 3.5 mm
      cortical screw with a core diameter of 1.9 mm in a correct position and in 9/113
      patients with the new 3.5 mm cortical screw with inner core of 2.4 mm in an
      incorrect position. CONCLUSION: Positioning screws require early removal only if
      they fail to loosen or if a persistent limitation of dorsiflexion is still
      present after three months.

PMID- 8273264
TI  - [The physician im malpractice cases].

PMID- 8273263
TI  - [Possibilities for HIV inactivation in homologous bone transplants].
AB  - Recently, the availability of bone allografts has declined dramatically, due to
      the three-month HIV test which is often difficult to obtain. Accordingly, there
      is a search for methods to inactivate HIV in bone allografts without compromising
      the biologic quality of the grafts. Chemical substances require long exposure and
      desorption times, to ensure that no toxic agents remain within the bone before
      actual transplantation. X-ray inactivation leads to complete loss of any
      osteoinductive properties of the allografts, according to some authors. In
      addition, the high doses that are necessary are difficult to apply. Autoclaving
      has been practiced in some instances, but all experimental results and some more
      recent clinical observations warn that osteoinductive properties of the
      allografts are lost during the autoclaving process. Lower temperatures (56
      degrees C) are sufficient to warrant inactivation of HIV, and some experimental
      results and preliminary clinical observations indicate that moderate heat
      treatment of bone allografts in a water bath may become a useful method for virus
      inactivation of bone allografts.

PMID- 8273265
TI  - Definition of the ideal tumor marker.
AB  - It is evident that the ideal tumor marker is not, nor should it be, a perfect
      tumor marker given the present level of our knowledge about prostate cancer.
      Further refinement of our information about prognosis and optimal treatment of
      this disease will ultimately lead to greater utility of many of the features of
      an ideal marker. On the other hand, the perfect tumor marker may become a moot
      issue if its development is overtaken by definitive information about prostate
      cancer etiology and prevention from the realm of molecular biology. Until that
      millennium is reached, we must continue to seek improvement in tumor markers that
      will permit us to take advantage of those features that are clinically useful at
      the current stage of our knowledge.

PMID- 8273266
TI  - Prostatic acid phosphatase. Biomolecular features and assays for serum
      determination.
AB  - Approximately 30 years ago, the finding that prostate acid phosphatase (PAP) was
      antigenically distinct from other acid phosphatases opened an era in the
      measurement of prostate cancer. Many immunoassays have been developed but their
      clinical significance has been limited. Studies comparing one or more assays in
      the same population of men with prostate cancer population have concluded that no
      differences were found in the sensitivities of the assays when the upper limits
      of normal were selected to provide equal specificities.

PMID- 8273267
TI  - Prostatic acid phosphatase in 1993. Its limited clinical utility.
AB  - The principal role of PAP determinations in 1993 with the ready availability of
      reproducible serum PSA determinations would be in the identification of those
      patients with clinically localized prostate cancer who will not be candidates for
      surgical cure because of the high likelihood of having pathologic stage C or D
      disease. However, if you believe that radical prostatectomy offers good local
      control and palliation for clinically localized but pathologic stage C or D
      disease, then preoperative PAP determinations are not necessary. Also, if you
      believe that radical prostatectomy in conjugation with androgen deprivation
      therapy is appropriate for clinically localized but pathologic stage D1 disease,
      then, again, preoperative PAP determinations are not necessary. However, if you
      believe that radical prostatectomy is indicated only for those patients with
      organ-confined cancer, then ordering a preoperative staging Roy enzymatic PAP
      assay is indicated. Therefore, every urologist must know the type of assay and
      the substrate being used by his/her laboratory to interpret the PAP results
      properly; otherwise, patients with potentially curable cancer will not be offered
      a radical prostatectomy. In conclusion, PSA is superior to PAP for diagnosis,
      screening, and monitoring prostate cancer. Even though there are three assays for
      PSA, there is less confusion in interpreting the results than for PAP. The only
      specific area where the enzymatic PAP assay can be useful is in the
      identification of those patients with clinically localized disease but
      pathologically extensive disease; this is not important if you believe that
      radical prostatectomy offers good local control and palliation for pathologic
      stage C and D1 disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273268
TI  - A conjugative plasmid pTE195 coding for drug resistance and virulence phenotypes
      from Salmonella naestved strain of calf origin.
AB  - Salmonella naestved strain AHI-195, of calf origin, harbors a conjugative 95
      megadalton (MDa) plasmid, pTE195, which encodes resistance to tetracycline and
      chloramphenicol and belongs to incompatibility group FII. Moreover, DNA homology
      between pTE195 and the Salmonella dublin virulence plasmid pTE800 was revealed by
      digestion with several restriction endonucleases and confirmed by hybridization
      with different specific probes. These results indicate that pTE195 carries not
      only genes for drug resistance but also genes for virulence phenotypes such as
      serum resistance and mouse lethality.

PMID- 8273269
TI  - Plasmids and outer membrane proteins of Yersinia enterocolitica and related
      species of swine origin.
AB  - Yersinia enterocolitica and other pathogenic yersiniae harbor a plasmid termed
      pYV which is required for the full expression of virulence. The pYV codes for the
      release of a set of proteins called Yops and two outer membrane proteins Yad A
      and Ylp A. In the present study, 80 strains of Y. enterocolitica and related
      species were examined for the possession of the pYV and the ability to express
      Yops and Yad A. Only Y. enterocolitica belonging to serogroups O:1,2,3, O:3,
      O:5,27, O:8, and O:9 harbored the virulence plasmid and were positive for the
      presence of the ancillary proteins. The restriction fragment patterns of the
      pathogenic bioserotypes belonging to the same serogroup affiliation were similar
      irrespective of whether they were of swine origin, reference strains, or human
      clinical isolates. The same was also true of the electrophoretic patterns of the
      Yops. Our findings are in agreement with previous studies and support the view
      that pigs may be an important reservoir of pathogenic Y. enterocolitica.

PMID- 8273270
TI  - Comparison of three biological assays for the detection of toxigenic properties
      of Bordetella bronchiseptica associated with atrophic rhinitis.
AB  - The toxigenic properties of Bordetella bronchiseptica strains associated with
      clinical atrophic rhinitis were compared using three biological assays: the
      guinea pig skin test, the mouse spleen atrophy and the suckling mice mortality
      assay. Forty one sick pigs were cultured and, in 20 of them B. bronchiseptica
      strains were isolated. Eighteen of the strains were toxigenic by at least one
      test. However, positivity did not always coincide amongst assays. This
      discrepancy raises the possibility of either differences in sensitivity between
      assays or the existence of more than one toxin.

PMID- 8273271
TI  - Comparison of serological tests for the diagnosis of Chlamydia psittaci infection
      of sheep.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed and compared with the
      complement fixation test (CFT) and the indirect immunofluorescence antibody test
      (IIFAT) for the detection of antibodies to C. psittaci in sheep. Field sera and
      experimental sera from aborting ewes, subclinically infected sheep and vaccinated
      sheep were used. The ELISA and IIFAT were much more sensitive than the CFT.
      Agreement between the CFT and ELISA varied between 50% and 98%, while agreement
      between the IIFAT and ELISA varied between 70.5% and 94.3%. The specificity of
      IIFAT and ELISA with regard to the identification of animals which may be a
      source of ovine abortion strains of C. psittaci was critically assessed, using
      antigen preparations derived from an abortion isolate and from a non-abortion
      isolate of C. psittaci. Indirect immunofluorescence was shown to be the more
      discerning test.

PMID- 8273272
TI  - The inhibition by ionophores in vitro of an Enterococcus-like pathogen of rainbow
      trout, Oncorhynchus mykiss.
AB  - Streptococcosis is a major disease of several fish species in Australia, Japan
      and South Africa. The minimum inhibitory concentration of some ionophores
      (lasalocid, monensin, narasin and salinomycin) was determined in vitro for an
      Enterococcus-like species pathogenic for rainbow trout (Oncorhynchus mykiss) in
      Australia. Forty isolates of the fish pathogen were tested, together with control
      strains of Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212 and
      Streptococcus bovis ATCC 9809. The minimum inhibitory concentrations (MIC) of
      erythromycin, the drug of choice for controlling streptococcosis, ranged between
      0.1 and 0.8 microgram/ml whereas the MIC values for the ionophores ranged between
      0.2 and 1.5 micrograms/ml. Of the ionophores tested, narasin was the most
      inhibitory (0.2-0.4 microgram/ml), while monensin was the least inhibitory (0.4
      1.5 micrograms/ml). Salinomycin was marginally more inhibitory (0.4-0.8
      microgram/ml) than lasalocid (0.8 microgram/ml).

PMID- 8273273
TI  - Optimalization of the detection of NAD dependent Pasteurellaceae from the
      respiratory tract of slaughterhouse pigs.
AB  - NAD dependent members of the family Pasteurellaceae were cultured from the nasal
      cavity, surface and cut surface of the tonsils, and from the apical and caudal
      lobes of the lungs of 303 slaughterhouse pigs from 5 different herds in order to
      obtain information on the ecology of these bacteria. The specimens were plated on
      two different selective agar media using a special dilution technique that
      resulted in a good separation of individual colonies. Bacteriological results
      were compared with serological and pathological findings. The bacteriological
      examination demonstrated that NAD dependent Pasteurellaceae belonging to the taxa
      previously described could be isolated from the surface and cut surface of the
      tonsils, and from lungs with and without gross pathologic lesions. Haemophilus
      parasuis was detected mainly from the nasal cavity, and Actinobacillus
      pleuropneumoniae mainly from the surface and cut surface of the tonsils (42%).
      From two herds, 19% and 24% respectively of the animals without antibodies
      against A. pleuropneumoniae serotypes 1 and 2 harboured the bacteria mainly in
      the tonsils. This may reflect a very recent infection or may suggest that A.
      pleuropneumoniae can colonize the tonsils without inducing a serologic reaction.
      Serological and bacteriological evidence of more than one serotype in the same
      herd indicates that natural infection with one serotype does not necessarily
      protect against another.

PMID- 8273274
TI  - The efficacy of tinidazole in naturally occurring periodontitis in dogs:
      bacteriological and clinical results.
AB  - The efficacy of tinidazole in addition to a single course of scaling was studied
      in 14 dogs with periodontitis. Three test teeth, two with periodontitis and one
      with healthy periodontium, were selected per dog. Subgingival bacterial samples
      were taken, and clinical examination was carried out at each of four visits (0,
      14, 90 and 180 days). The bacterial samples were cultured anaerobically using
      selective and nonselective media. All teeth in the dentition, except one diseased
      test tooth with periodontitis were scaled at the first visit and tinidazole or
      placebo administered twice a day for 7 days. The mean probing depth of the
      diseased test pockets was significantly more reduced in tinidazole+scaling (T1S1)
      than scaling alone (T0S1) group at all visits compared to baseline values. The
      most significant decreases of bacterial counts in T1 or T0 groups were found in
      agar corroding Gram-negative rods in both diseased and healthy T1S1 pockets and
      in slimy Gram-negative rods in diseased T1S0 pockets between visits 1 and 2. The
      intergroup comparisons showed that Gram-positive cocci decreased significantly
      more in S1 pockets as well as sporeforming Gram-positive rods in diseased S0
      pockets of T1 than T0 group. The highest number of isolates was found in the
      group of pigmented Gram-negative anaerobe rods, mainly Porphyromonas spp. The
      percentage of Porphyromonas gingivalis-like isolates decreased to zero and
      Porphyromonas endodontalis-like isolates increased in all test teeth of T1 group
      at 14 days. It is concluded that tinidazole has good efficacy against P.
      gingivalis-like bacteria which seem to be periodontal pathogens in dogs.

PMID- 8273275
TI  - Adaptation of the Sensititre broth microdilution technique to antimicrobial
      susceptibility testing of Mycoplasma hyopneumoniae.
AB  - A broth microdilution technique is described for determining the antimicrobial
      susceptibility of Mycoplasma hyopneumoniae, using commercially prepared
      Sensititre plates. Twenty-five field isolates and two reference strains (J &
      232), were tested against seven antimicrobials. Field isolates were tested in
      duplicate and reference strains, four times to estimate reproducibility. Ninety
      seven percent of the duplicate MIC results for the field isolates were in
      agreement, or within one log2 dilution. Similar results were obtained with the
      reference strains. The isolates were susceptible to lincomycin-spectinomycin,
      tylosin and oxytetracycline or resistant to amoxycillin, apramycin and
      erythromycin. Susceptibility to furaltadone varied. This method retains the
      accuracy and reproducibility of broth MIC determinations, while avoiding the
      lengthy preparation of antimicrobial dilutions normally associated with more
      traditional methods.

PMID- 8273276
TI  - Antibody response elicited against empty reticuloendotheliosis virus particles in
      two inbred lines of chicken.
AB  - Immunisation of Houghton White Leghorn line 15I and 6(1) chickens with empty
      reticuloendotheliosis virus particles elicited a primary antibody response which
      is probably directed against the viral envelope glycoproteins gp73/71 and gp22.
      Antibodies in line 15I birds were shown to be non-neutralising and did not
      protect against the tumourigenic effects of reticuloendotheliosis virus, strain
      T. However, immunised line 6(1) chicks did not exhibit the runting syndrome
      associated with reticuloendotheliosis virus infection, suggesting that antibody
      against viral coat proteins may play a role in modulating pathogenesis in certain
      lines of chicken.

PMID- 8273277
TI  - Antigenic and biological diversity among transmissible gastroenteritis virus
      isolates of swine.
AB  - Twenty-four field isolates of transmissible gastroenteritis virus (TGEV) were
      isolated and examined for antigenic and biological characteristics. Most TGEV
      isolates produced a typical cytopathic effect (CPE) in swine testis (ST) cell
      culture, which included a ballooning or lifting away of the infected cells from
      the cell monolayer with heavy granulation evident. Minor variations in CPE were
      observed with one isolate, IA-145. Protein profiles of the TGEV isolates as
      determined by SDS-PAGE were essentially identical, with the exception of the
      isolate IA-101. The TGEV isolate IA-101 presented a higher molecular mass M
      protein and lacked an N protein doublet that was present in all other TGEV
      isolates. The TGEV isolates were shown to be closely related antigenically by
      using hyperimmune sera in a virus neutralization (VN) test. Some antigenic
      diversity was detected by utilizing monoclonal antibodies (mAbs) in a VN test.
      Titers of the mAbs were highest with the homologous Miller TGEV, and one virus
      isolate, IA-156, was very poorly neutralized with the mAbs used in this study.
      Indirect immunofluorescence assay (IFA) results were similar to those obtained by
      the VN test. These studies show that some biologic and antigenic diversity exists
      among TGEV isolates.

PMID- 8273278
TI  - Isolation of bluetongue virus serotype 21 from Culicoides spp. in Indonesia.
AB  - The isolation of a bluetongue (BLU) virus from Culicoides spp. in Indonesia is
      reported. BLU serotype 21 was isolated from a mixed pool of C. fulvus and C.
      orientalis of the Avaritia subgenus.

PMID- 8273279
TI  - The effect of the mode of sampling on BHV-1 detection in infected cattle by dot
      blot hybridization.
AB  - The BHV-1 genome in nasal swabs and washings was detected by dot-blot
      hybridization using the 32P-pUR-1 probe (1.8 kb EcoRI-HindIII random fragment of
      BHV-1 DNA ligated into the pUC-9 plasmid) as early as on day 1 after the
      experimental infection of cattle. In dependence on the sampling method,
      differences were observed in the maximum of hybridization signals. During nasal
      swab analyses maximum amounts of BHV-1 differed in the individual samples (day 1
      3). Hybridization signals obtained at the analysis of BHV-1 DNA nasal washings
      did not vary but showed a continuous maximum on day 2 after infection. Nasal
      washings proved to be more advantageous for detection of the BHV-1 genome by the
      hybridization technique.

PMID- 8273280
TI  - Structural difference in the fusion protein among strains of bovine respiratory
      syncytial virus.
AB  - The polypeptides of different strains of bovine respiratory syncytial virus (RSV)
      were compared. Altered electrophoretic migrations were observed in the G, F, P, M
      and 22 kDa polypeptides. The molecular weight of the F2 fragment in human RSV
      (Long strain) and bovine RSV (A51908 and Md-X strains) was approximately 20 kDa
      whereas it was approximately 15.5 kDa in caprine RSV and bovine RSV (FS-1 and VC
      464 strains). The size difference of the F2 subunit was due to difference in the
      extent of glycosylation.

PMID- 8273281
TI  - Polymerase chain reaction and partial sequencing of a British isolate (T637) of
      feline immunodeficiency virus.
AB  - We have used the polymerase chain reaction (PCR) and direct sequencing of the
      amplified products to obtain information of the molecular nature of an FIV
      isolate, T637. Cats experimentally infected with T637 have progressed to clinical
      immunodeficiency disease. The 5' long terminal repeat (LTR), most of the genes
      coding for internal proteins (GAG) and surface proteins (ENV), and part of the
      polymerase (POL) gene have been sequenced. The LTR of T637 has 92% nucleic acid
      identity with the prototype strain, FIV-Petaluma and the Glasgow isolate, FIV-14,
      89% with a Swiss isolate, FIVZ2, and 95% with the PPR isolate. Both GAG and POL
      genes of T637 share extensive homology with Petaluma and PPR. In the ENV gene,
      T637 has 91% nucleic acid homology with Petaluma and 86% with PPR, and an overall
      amino acid homology of between 81-87%. For the surface (SU) region of the ENV
      gene product, T637 has 89% amino acid homology with Petaluma and FIVZ2 and 86%
      with PPR.

PMID- 8273282
TI  - Complement-dependent serum neutralization with virulent and avirulent Bucyrus
      strains of equine arteritis virus.
AB  - Virulent and avirulent strains of Bucyrus equine arteritis virus (EAV) were used
      to raise antiserum in horses. Serum neutralization (SN) tests were performed with
      and without the addition of guinea pig complement. The inclusion of ten percent
      guinea pig serum in the virus suspension was sufficient for optimal enhancement
      of SN titres at any immune stages after immunization. Immune serum prepared
      against avirulent virus reacted only with homologous virus and there was no
      complement enhancement. Immune sera raised against live or inactivated virulent
      virus neutralized both virulent and avirulent virus. The reaction with virulent
      virus demonstrated complement enhancement. There was also moderate potentiation
      in the presence of complement when serum raised against inactivated virulent
      virus reacted with avirulent virus.

PMID- 8273283
TI  - Dipstick enzyme immunoassay for rinderpest antibody in cattle.
AB  - A dipstick enzyme immunoassay (ELISA) has been standardized for the detection of
      rinderpest antibodies. One hundred and thirty bovine serum samples were analysed
      by the dipstick ELISA method and the results compared with the conventional plate
      ELISA method. The sensitivity was found to be similar in both methods. The
      dipstick ELISA does not require expensive micro-plates and an ELISA reader, and
      is recommended for use in field laboratories where the qualitative detection of
      rinderpest antibodies is required.

PMID- 8273284
TI  - Serotonergic, 5-HT2, receptor-mediated phosphoinositide turnover and mobilization
      of calcium in cultured rat retinal pigment epithelium cells.
AB  - Cultured rat retinal pigment epithelium cells are shown to contain serotonergic,
      5-HT2, receptors associated with phosphoinositide turnover and mobilization of
      intracellular calcium. Serotonin at a concentration of 10 microM induced a 2.5
      fold increase in [3H]-inositol phosphates (more than 75% is in the form of [3H]
      inositol-1-phosphate) accumulation within 30 min in cells preincubated in [3H]
      myo-inositol and exposed to 5 mM lithium chloride. The EC50 value of serotonin
      was approx. 0.9 microM and the saturation concentration was 100 microM. Serotonin
      analogues like tryptamine, 5-methoxytryptamine, alpha-methyl-serotonin and the 5
      HT2 agonists quipazine and DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane)
      all stimulated InsPs accumulation to some degree. Carbachol, noradrenaline,
      isoproterenol, dopamine, tryptophan, 5-hydroxytryptophan, 8-hydroxy-2(di-n-propyl
      amino) tetralin, 2-methyl-serotonin and NECA (5'-[N-ethyl]-carboxamidoadenosine)
      were inactive. The serotonin-induced response was blocked most effectively by
      ketanserin and methysergide but not by 5-HT3 or 5-HT1 antagonists. The serotonin
      response was attenuated by the active phorbol ester, 4 beta-phorbol 12-myristate
      13-acetate and this was attenuated by the non-selective protein kinase C
      inhibitor, staurosporine. Pertussis toxin failed to influence the serotonin
      mediated phosphoinositide turnover. Addition of serotonin to cultures loaded with
      Fura-2 showed a transient increase in calcium concentrations in most of the
      cells. This change in calcium was independent of external calcium and the
      serotonin response was attenuated by ketanserin but not by the 5-HT3 antagonist
      granisetron.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273285
TI  - pH regulation in frog cones studied by mass receptor photoresponses from the
      isolated retina.
AB  - Mass cone photoresponses were recorded across the aspartate-treated frog retina
      under treatments chosen to affect putative pH-regulating mechanisms. The
      saturated response amplitude (Umax) was found to be a monotonically increasing
      function of perfusion pH in the range 7-8, and thus presumably of intracellular
      pH (pHi). Accepting that Umax can be used as an index of pHi changes, two results
      indicate the importance of bicarbonate transport for preventing intracellular
      acidification: (1) bicarbonate-buffered (6 mM HCO3- + 6 mM HEPES) perfusate
      increased Umax compared with nominally bicarbonate-free perfusate (12 mM HEPES);
      (2) the anion transport blocker DIDS (0.1 mM) caused a strong decrease in the
      amplitude of photoresponses. Substitution of 95 mM chloride by gluconate in the
      perfusing fluid boosted photoresponses indicating that at least part of the
      bicarbonate transport involves HCO3-/Cl- exchange. Amiloride (2 mM) also caused a
      decrease of photoresponse amplitude, which suggests that Na+/H+ exchange
      contributes to pHi regulation. In all these respects, cones behaved similarly to
      rods. Cones differed from rods (in the intact retina) in that addition of 0.5 mM
      of the carbonic anhydrase inhibitor acetazolamide reduced (never augmented)
      photoresponses. The difference is considered in relation to the presence of
      carbonic anhydrase in cone, as opposed to rod, outer segments.

PMID- 8273286
TI  - Anisotropies in the perception of stereoscopic surfaces: the role of orientation
      disparity.
AB  - We measured stereoscopic slant detection thresholds for surfaces slanting about a
      horizontal or a vertical axis. For random-dot covered surfaces, 1.25 deg of slant
      was required to detect slant about a horizontal axis, whereas 2.1 deg of slant
      was required to detect slant about a vertical axis. This anisotropy could be due
      to the fact that orientation disparities, which contain information about surface
      slant, are generally smaller for surfaces slanting about a vertical axis. To test
      this possibility, slant thresholds were measured for surfaces whose orientation
      disparity content was manipulated independently of the other slant information
      present. When the magnitude of orientation disparity was the same for surfaces
      slanting about a horizontal and a vertical axis, both surface orientations
      required about 1.5 deg of slant to be detected; thus the anisotropy became
      negligible. In contrast, when the orientation disparity content of a surface
      slanting about a vertical axis was zero, 3-4 deg of slant was required for
      detection; thus the anisotropy became larger. Under the conditions of these
      experiments, it appears that the visual system utilizes orientation disparities.

PMID- 8273287
TI  - Cone pathways and the pi 0 and pi 0' rod mechanisms.
AB  - The field-adaptation properties of two scotopic (rod) mechanisms, pi 0 and pi 0',
      were measured to test a two-pathway model that associates the fast temporal
      properties of pi 0' with the processing of rod signals by early cone pathways,
      possibly including cone photoreceptors, and the sluggish temporal properties of
      pi 0 with processing of rod signals by classical rod pathways. This model
      predicts that cone stimulation will differentially affect the flicker sensitivity
      of pi 0' compared to pi 0. Both rod mechanisms are seen in double-branched
      flicker-threshold-vs-intensity (FTVI) curves measured with a 15-Hz, square-wave
      modulated, rod-detected test stimulus. We show that the position of the upper
      branch (pi 0') shifts relative to the lower branch in response to changes of
      background wavelength, indicating that different receptor types regulate
      sensitivity of pi 0 and pi 0'. Field spectral sensitivity (FSS) functions for pi
      0 closely match the scotopic spectral sensitivity function, indicating that only
      rods adapt pi 0 under these conditions. In contrast, fitting of FSS functions for
      pi 0' required a combination of cone and rod spectral sensitivity functions. The
      relative adaptational effect of cone stimulation compared to rod stimulation
      increases with background light level: at highest levels, cone stimulation has
      more influence than rod stimulation. Test additivity experiments assessed the
      degree of additivity between cones and rods to ensure that the pi 0' branch did
      not result from sub-threshold summation between receptor mechanisms.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8273288
TI  - Detection and discrimination of curvature in foveal and peripheral vision.
AB  - Curvature detection and discrimination were measured across the visual field in
      order to determine whether performance at a given eccentricity could be related
      to that at another by a simple change of magnification. Both types of task obeyed
      this concept, the critical variable being the rate at which magnification must
      increase as a function of eccentricity. The situation can be expressed in terms
      of the eccentricity (E2) at which magnification must be doubled to retain
      performance equivalent to that at the fovea. E2 values were 1.84-1.96 deg for the
      detection task and 1.42-2.27 deg for discrimination. These are similar to E2
      values for vernier acuity and orientation discrimination, suggesting that all of
      these tasks share a common determining feature across the visual field, perhaps
      the distribution of neural elements selective for stimulus orientation.

PMID- 8273289
TI  - Spatial localization of motion-defined and luminance-defined contours.
AB  - Thresholds for the vernier alignment of contours defined by luminance and
      coherent random-dot motion were measured. The luminance-defined contours were
      localized with a precision better than the receptor grain, while the motion
      defined contours were localized more poorly than this limit. When motion-defined
      and luminance-defined targets were matched for dot density, vernier thresholds
      were equivalent at low densities. When the targets were also equated for
      perceived contrast, the vernier thresholds became equivalent at higher densities
      as well. These results suggest that the precision with which motion-defined
      contours are localized is contrast and sample limited. Next, the localization
      mechanism for motion-defined targets was investigated. Length summation limits
      were similar for motion-defined and luminance-defined targets, suggesting that
      these targets could be localized by a common mechanism. Vernier targets were then
      flanked by two additional bars. Motion-defined flanks interfered with the
      localization of motion-defined targets and luminance-defined flanks interfered
      with the localization of luminance-defined targets. However, motion-defined and
      luminance-defined bars did not interact to produce spatial interference. This
      result indicates that the mechanisms for localizing luminance-defined and motion
      defined targets are independent. We suggest that parallel mechanisms govern the
      vernier localization of motion-defined and luminance-defined targets.

PMID- 8273291
TI  - The role of edges and line-ends in illusory contour formation.
AB  - Illusory contours can be induced along directions approximately colinear to edges
      or approximately perpendicular to the ends of lines. Using a rating scale
      procedure we explored the relation between the two types of inducers by
      systematically varying the thickness of inducing elements to result in varying
      amounts of "edge-like" or "line-like" induction. Inducers for our illusory
      figures consisted of concentric rings with arcs missing. Observers judged the
      clarity and brightness of illusory figures as the number of arcs, their
      thicknesses, and spacings were parametrically varied. Degree of clarity and
      amount of induced brightness were both found to be inverted-U functions of the
      number of arcs. These results mandate that any valid model of illusory contour
      formation must account for interference effects between parallel lines or between
      those neural units responsible for completion of boundary signals in directions
      perpendicular to the ends of thin lines. Line width was found to have an effect
      on both clarity and brightness, a finding inconsistent with those models which
      employ only completion perpendicular to inducer orientation.

PMID- 8273290
TI  - Transient and sustained components of the pupil response evoked by achromatic
      spatial patterns.
AB  - The present study provides new clues about visual processes underlying the human
      pupillary responses evoked by achromatic spatial patterns. The pupillary
      responses can be modeled as a combination of two processes, a temporally
      transient process which saturates with increasing contrast and a temporally
      sustained process which varies linearly with increasing grating contrast. The
      transient process has low-pass, whereas the sustained process has a middle band
      pass spatial filter characteristic. the results support the hypothesis that the
      visual input to the pupillomotor nuclei is composed of phasic and tonic visual
      neurons that are functionally similar to those in the magno (M)- and parvo (P)-
      cellular layers in the lateral geniculate nucleus.

PMID- 8273292
TI  - Link-specific adaptation in the luminance and chromatic channels.
AB  - We present evidence that adaptation occurs in the separate links that connect the
      receptors to the luminance and the chromatic channels. The relative effectiveness
      of the L and M cone inputs to the luminance and red/green chromatic channels was
      determined by using, respectively, heterochromatic flicker photometry and a
      cancellation technique which maintained a pure yellow. The findings provide
      evidence for a link-specific adaptation model, wherein one receptor system
      provides two separate links to the luminance and chromatic channels and the
      outputs of an individual cone to these two postreceptoral channels can be
      separately attenuated or weighted at each of these links by colored adapting
      lights. One line of evidence for link-specific adaptation is that colored
      adapting fields selectively suppress L and M cone inputs to the red/green
      chromatic channel by a smaller factor than the luminance channel. A second line
      of evidence is that there is not only a magnitude difference but also a dynamic
      difference between adaptive processes operating in the luminance and chromatic
      channels: the luminance channel has a faster gain change and recovery from
      adaptation than does the chromatic channel. The results, together with other
      evidence, make it plausible that an important component of light adaptation in
      cone vision occurs at the cone-bipolar synapse.

PMID- 8273293
TI  - Initial performance, learning and observer variability for hyperacuity tasks.
AB  - Psychophysically-experienced and -inexperienced human observers were tested on 34
      different non-stereo and 49 stereo hyperacuity stimuli. Performance reached
      hyperacuity levels within the first five trials for the non-stereo stimuli. For
      stereoacuity tasks the results were very different. Even extremely experienced
      observers with very low thresholds for certain stereo tasks required considerable
      practice to achieve their best performance for slightly different stereo tasks.
      Performance on both types of tasks showed considerable observer variability.
      These results suggest that adults do not synthesize new visual modules for
      hyperacuity tasks early in the visual pathway on a task-driven basis. We also
      interpret these results to suggest that there can be many equally general models
      of hyperacuity performance that show only the qualitative general trends of a
      "standard" observer. Incorporating individual variability might provide
      sufficient constraints on such models to provide clues about physiological
      mechanisms.

PMID- 8273294
TI  - Contrast sensitivity and vernier acuity in amblyopic monkeys.
AB  - Human psychophysical studies suggest that strabismic and anisometropic amblyopes
      may have characteristically different patterns of visual loss. In particular,
      anisometropic amblyopes often show deficits on spatial localization tasks that
      scale with their spatial resolution losses, whereas strabismic amblyopes can show
      localization deficits that are large relative to their losses in spatial
      resolution. We have compared the performance of non-human primates with
      experimentally-induced anisometropic and strabismic amblyopia on contrast
      detection and vernier acuity tasks. The performance of both groups of animals was
      fundamentally similar: both strabismic and anisometropic monkeys showed deficits
      in spatial localization that were large relative to their resolution losses,
      although the animals with the most disproportionate losses were strabismic. We
      investigated the extent to which contrast sensitivity losses accounted for the
      vernier acuity deficits. The results showed that, in most cases of either
      strabismic or anisometropic amblyopia, when the vernier stimuli for each eye were
      equated in terms of effective contrast, the extent of the vernier acuity deficit
      was reduced to approximately the extent of the spatial resolution deficit. In two
      cases, both of strabismic amblyopia, we found that equating the stimuli in this
      way was not sufficient to make the deficits equal, a pattern that has been
      described for human strabismic amblyopes.

PMID- 8273295
TI  - Color enhances Mach bands detection threshold and perceived brightness.
AB  - We have previously argued that unless color and luminance are shown to be
      processed independently, using isoluminant stimuli may not reveal the full
      contribution of color to visual functioning. Here we study the interaction of
      color and luminance in a task, Mach bands detection and perceived brightness,
      where color by itself is not effective at all. Subjects viewed luminance or
      color/luminance ramps and had to determine in either case the luminance contrast
      necessary for detecting Mach bands and, in another experiment, to compare the
      brightness of the bands in the luminance and in the combined displays.
      Isoluminant color displays did not generate any Mach bands, but the addition of
      color to the luminance display lowered Mach bands detection thresholds and
      enhanced their perceived brightness. It is thus concluded that the failure to
      perceive Mach bands in an isoluminant display is not indicative of the lack of
      color contribution to spatial vision but rather indicates that the strong effect
      that color has on contrast enhancement mechanisms can be revealed if color and
      luminance are allowed to interact.

PMID- 8273296
TI  - Relative contributions of optical and neural limitations to human contrast
      sensitivity at different luminance levels.
AB  - The relative contributions of optical and neural constraints on human contrast
      sensitivity as a function of spatial frequency were assessed for a range of
      luminances. First, the overall two-dimensional contrast sensitivity function
      (CSF) was obtained for three eyes at three luminances (0.05, 0.5 and 20 cd/m2)
      using a standard two-alternative forced-choice procedure. Second, the two
      dimensional modulation transfer function (MTF) of the optics was measured for the
      same eyes and pupil sizes using a hybrid optical-digital method. The two
      dimensional neural transfer function (NTF) was obtained as the ratio between the
      CSF and the MTF. Minor factors, such as the effect of cone aperture, were also
      considered in the computations. Our results show that at all luminances, the fall
      off in contrast sensitivity at high spatial frequencies is mainly due to optical
      factors. The losses in contrast sensitivity with decreasing luminance are,
      however, primarily due to noise limitations.

PMID- 8273297
TI  - Phosphor persistence in oscilloscopic displays.

PMID- 8273298
TI  - Transparent surfaces defined by implicit X junctions.
AB  - An X junction is known to be a strong cue for transparency whereas a T junction
      typically indicates occlusion by an opaque surface. In this article, however, we
      will demonstrate two cases in which special T junctions (implicit X) can support
      the perception of a transparent surface. The T junction is perceived as having an
      additional illusory contour rendering it as an implicit X junction. There is
      physically realizable condition in which transparency can produce a T junction
      and the existence of this special case may explain why T junctions are not
      necessarily taken as cues for opaque surface. The similar processing for X
      junctions and implicit Xs to form transparent surfaces is suggested.

PMID- 8273299
TI  - Local direction of edge motion causes and abolishes the barberpole illusion.
AB  - The perceived direction of motion of a one-dimensional grating is measured in
      straight-edged rectangular and indented rectangular apertures. It is shown that
      the perceived direction of motion of the pattern is largely determined by the
      directions of motion at the edges, rather than by the aspect ratio or global
      shape of the aperture. The edge motion vectors appear to be calculated at a
      remarkably local scale. The barberpole illusion is abolished when indentation
      size equals or exceeds one-quarter of the grating period. This critical size is
      scale invariant with grating period and corresponds well with a quadrature model
      of motion perception.

PMID- 8273300
TI  - An adaptation-induced pop-out in visual search.
AB  - The present study demonstrates that an object embedded in an array of identical
      objects can pop-out. Dependent on the stimuli preceding the search display, local
      (chromatic) adaptation causes an identical object to pop-out because it appears
      to have a colour (Expt 1) or brightness (Expt 2) that is slightly different from
      the colour and brightness of the other objects in the display. Experiment 3 shows
      that this pop-out even occurs when the stimulus preceding the search display is
      presented for only 100 msec.

PMID- 8273301
TI  - Binocular correlates of the direction of motion in depth.
AB  - Two binocular cues to the direction of an object's motion in depth are the ratio
      (phi R/phi L) between the velocities of the object's retinal images in the right
      and left eyes and the ratio (phi/gamma) between the velocity of the binocularly
      fused image of the object and the rate of change of disparity. We report that the
      apparent direction of motion in depth of a monocularly-camouflaged target can be
      varied by altering the ratio phi/gamma. Because no monocular motion signal is
      available in this case, we conclude that the ratio phi/gamma is a sufficient cue
      to the direction of motion in depth. This is not to deny that the phi R/phi L cue
      might be used in the everyday visual situation where monocular velocities phi R
      and phi L are available to the brain.

PMID- 8273302
TI  - Quantitative modeling of responses of anuran retina: stimulus shape and size
      dependency.
AB  - Teeters and Arbib presented a model of the anuran retina which qualitatively
      accounts for the characteristic response properties used to distinguish ganglion
      cell type in anurans. In this paper we test the model's ability to reproduce
      quantitatively tabulated data on the dependency on stimulus shape and size, with
      a new implementation of the model in the neural simulation language NSL. Data of
      Ewert and Hock relating toad R2, R3, and R4 ganglion cell responses to moving
      worm, antiworm, and square-shaped stimuli of various edge lengths are used to
      test stimulus shape and size dependency. A close match to the data can be
      achieved by tuning some of the model parameters while still retaining the
      characteristic responses to the typical stimulus types. We stress here the
      importance of a populational approach to the models. We place more emphasis on
      the variation of response properties in a population of neurons of the same
      class, rather than questing for the neuron of a given type. As an example of the
      populational approach we offer a model for the respiratory R3 response following
      researchers who argue that a subclass of R3 neurons are activated by stationary
      boundaries owing to the anuran's self induced respiratory eye movement.

PMID- 8273303
TI  - [Hypertension in patients with post-streptococcal glomerulonephritis].
AB  - Sixty two patients with poststreptococcal glomerulonephritis (PSGN), aged 18-22
      (mean = 19 +/- 0.5 years) were examined and treated at the Clinic of Nephrology
      of the M.M.A. from the beginning of 1986 to the end of 1990. Hypertension
      (diastolic pressure over 13 kPa, that is, 97.5 mmHg) in the acute phase was found
      in 59 (95.16%) patients, being of milder degree and short-term course. Transient
      increase of blood pressure required sometimes a short therapy (with furosemide
      mainly). With normalization of the glomerular filtration rate, withdrawal of
      edema, and normalization of the plasma volume, the blood pressure has been also
      normalized in the majority of patients (within 3-5 days). Observing PSGN
      evolution in the period from 2 to 5 years, hypertension was found in 3 (6.8%) of
      44 patients. All three patients had the clear clinical evolution (proteinuria and
      erythrocyturia) without signs of renal insufficiency. The rebiopsy of the kidneys
      showed milder morphologic changes which were more manifested compared to the
      group without hypertension. Hypertension was present in the majority of patients
      in acute phase of PSGN while it was rarely found during the evolution of the
      disease and its presence has been poor prognostic sign in evolution since it
      contributed to development of glomerulosclerosis and later on renal
      insufficiency.

PMID- 8273304
TI  - [Frequency of positive ergometric findings in officers of the Yugoslav Army with
      subjective heart problems].
AB  - Ergometric testing was performed in 96 officers of the Yugoslav Army, aged 30-59,
      with subjective troubles in the heart region and normal findings obtained by
      routine diagnostic procedures. In 36 examined officers (37.5%) ergometric finding
      was normal. In the rest of them, four different types of abnormal reactions of
      the cardiovascular system to exercise were recorded: myocardial ischemia (48.3%),
      abnormal reaction of blood pressure (24.1%), abnormal heart rates (16.1%) and
      extrasystoles (11.5%). The statistically significant correlation was found
      between subjective troubles in the heart region and positive ergometric findings.

PMID- 8273305
TI  - [Immediate results of surgical treatment of intracardiac myxomas in 45 patients].
AB  - Between 1961 and 1992, 45 patients with intracardiac myxomas localised in the
      left ventricle--40 (89%) and in the right ventricle--5 (11%) were operated on.
      There were 27 women and 18 men, aged 15-63, mean age, 46.5 years. Three patients
      were asymptomatic while in other dominated different degree of malfunction of the
      corresponding atrioventricular valve, mainly with dominant symptoms and signs of
      stenosis. In 5 patients (11%) myxoma of the left atrium was in question together
      with systemic embolization. The diagnosis was established both by invasive and
      noninvasive methods and the method of choice, very reliable and easy, has proved
      to be echocardiography. All patients were operated on with the use of the total
      cardiopulmonary bypass and induced heart arrest. The histologic verification of
      all excised myxomas was performed. Three early deaths occurred (6.6%), while in
      other patients no postoperative complications developed. It has been concluded
      that echocardiography is very safe diagnostic procedure and results of surgical
      treatment are very good.

PMID- 8273306
TI  - [Clinical characteristics of Lyme disease].
AB  - Clinical characteristics of Lyme disease were analysed in 22 patients. Erythema
      migrans was found in 20 (91%), arthralgia in 18 (81%), neuralgia in 8 (36%),
      encephalitis in 3 (13%), carditis in 2 (9%) and arthritis in 2 (9%) patients. The
      positive antibody titer was found in 14 (63%) patients. Favourable effects of
      antibiotic therapy was achieved in all patients. Erythema migrans has been
      manifested up to 12 days after tick sting and arthralgia, arthritis, neuralgia,
      hepatitis and chronic dermatitis within a year. Carditis and encephalitis have
      been developing from a month to ten years after tick sting. Lyme borreliosis is
      commonly manifested as a systemic disease. Together with the skin, most commonly
      have been involved ankle joints, heart and nervous system. The time from tick
      sting to the onset of first signs of the diseases varies by the involved organs.

PMID- 8273307
TI  - [Determination of albendazole and its main metabolite albendazole sulfoxide in
      the hydatid fluid of human echinococcal cysts using HPLC].
AB  - Concentrations of albendazole and its active metabolite in echinococcal cyst of
      the human liver were determined in order to evaluate drug effects of the decrease
      of protoscolex vitality. Albendazole concentration of 0-64.9 micrograms/ml and
      albendazole sulfoxide of 0-40.8 micrograms/ml were found in cysts. The
      protoscolexes showed markedly manifested morphologic changes up to the
      disintegration. The postoperative follow up of patients within 24 months
      discovered no recidives of the disease and the patients were regarded as cured.
      On the basis of the results obtained it has been concluded that the use of
      albendazole in the dose of 800 mg/day within 28 day is sufficient for achievement
      of therapeutic drug level in vivo conditions.

PMID- 8273308
TI  - [Neurophysiologic tests for the early detection of deafness in children].
AB  - Using brainstem auditory evoked potentials and tympanometry the authors have
      examined 120 children aging from several months to five years and they have found
      a high percentage of children with hearing impairment with sensorineural
      deafness. The children had also secretory inflammation of the middle ear. It has
      been suggested that secretory inflammation of the middle ear deteriorates the
      basic hearing impairment because of which it should be early diagnosed and
      surgically treated. Owing to the complex problem of children deafness, the
      authors recommend that several methods of examination should be applied in the
      diagnostic procedure in order to determine precisely the auditory threshold and
      to initiate in time hearing and speech habilitation.

PMID- 8273309
TI  - [The effect of hypoxia and mental stress on the distribution of energy in the
      phoneme "A"].
AB  - Considering the fact that one of the indicators of effects of hypoxia in pilots
      could be an altered speech we have analysed changes in uttering a sound (A) in
      our examinees, pilot-students, aged 21-23, under effects of hypoxia only, the
      associated effects of hypoxia and mental loading and under conditions of normal
      barometric pressure. In the frequency and three dimensional representation of the
      selected sound, there have been analysed frequency components, intensity,
      duration and quality of the sound. It has been found that acute hypoxia causes
      deep structural and durational changes. During the stay at the simulated altitude
      the contributing factor to these changes which should be taken into account is
      the mental loading--performance of the test. It has been obvious that the same
      degree of hypoxia associated with mental activities during test performance
      causes deeper degradation of the voice structure both in the resistant subjects,
      and especially in individuals sensitive to the lack of oxygen compared to that
      under effects of hypoxia only and that under physiologic conditions.

PMID- 8273310
TI  - [Epidemiologic characteristics of stomach cancer in Belgrade].
AB  - Stomach cancer mortality in the period 1975-1990 in Belgrade has been analysed.
      In a sixteen-year period the mean standardised stomach cancer mortality rate was
      11.4 per 100,000 inhabitants (males-14.8%000: females-8.6%000). The specific
      mortality rate by age shows low values before age 34, then it comes to its sudden
      increase reaching the highest rate in subjects after age 75. Standardised stomach
      cancer mortality rate by age in the observation period 1975-1990 showed a mild
      increase in males (y = 14.16 + 0.08x) and an insignificant decrease in females (y
      = 8.80-0.02x). The percentage of gastric cancer in all causes of death, all
      malignant tumours and malignant tumours of the digestive tract, shows a
      decreasing trend.

PMID- 8273311
TI  - [Classification of injuries--measurement of injury severity].

PMID- 8273312
TI  - [Measurement of severity of war injuries in the field using the Red Cross
      classification system].

PMID- 8273313
TI  - [Rationale for the use of antioxidants in neurology].

PMID- 8273314
TI  - [Retroviruses in dermatology].

PMID- 8273315
TI  - [Diagnosis and surgical treatment of intra-orbital wooden foreign bodies].

PMID- 8273317
TI  - Papillary cystic tumours of the pancreas.
AB  - Papillary cystic tumour is an uncommon neoplasm of the pancreas which has only
      been described recently. This report describes five such cases seen at the
      University Hospital of the West Indies (UHWI). The clinico-pathological features
      were typical in all these cases. The literature of this condition is also
      reviewed.

PMID- 8273316
TI  - Ultrastructure of the islets of Langerhans in protein-energy malnutrition.
AB  - Significant hormonal changes have been reported in childhood malnutrition,
      including high serum levels of growth hormone and cortisol, and low levels of
      circulating insulin. The ultrastructure of the endocrine pancreas in such
      patients has hitherto not been reported. A light microscopy survey of the
      pancreatic islets was carried out on 69 malnourished children dying from protein
      energy malnutrition. In seven of these cases, a rapid autopsy protocol allowed
      tissues to be fixed for electron microscopy within 75 minutes of death. This
      paper presents the first ultrastructural observations on the Islets of Langerhans
      in childhood protein-energy malnutrition. In all cases, there was a variable
      degree of degeneration of all cell types with membrane damage, loss of ribosomes,
      vesiculation and mitochondrial swelling. In addition, the B-cells showed a high
      proportion of precursor granules compared to crystal forms, possibly accounting
      for low insulin serum levels reported by other workers. It is suggested that
      islet cell changes may be related to free radical damage secondary to depletion
      of glutathione and other antioxidants, as well as relative deficiencies of
      cysteine and zinc. In addition, the effects of agonal anoxia, and a short
      fixation delay after death must be considered.

PMID- 8273318
TI  - Evaluation of methods for the laboratory diagnosis of malaria in Guyana.
AB  - When 297 blood samples taken from patients attending a fever clinic in Georgetown
      Public Hospital were examined microscopically, after thick and thin blood films
      had been stained with Giemsa, one hundred and forty-two (47.8%) were
      microscopically positive for malaria. After processing the patient's serum,
      samples by the Indirect Fluorescent Antibody (IFA) technique, specific IgG and
      IgM antibodies were detected in 239 (81.3%) and 179 (60.1%), respectively, of the
      sera. Based on the microscopical findings, the IFAT gave positive predictive and
      negative values of 54.4% and 81.8% (IgG), and 57.5% and 67.8% (IgM), suggesting
      that the IgM would be more useful than the IgG in the diagnosis of current
      malaria. An odds ratio analysis showed that the presence of symptoms, IgG or IgM
      antibodies, as well as visits to endemic regions, could be good indicators of
      current malaria. Age and occupation were not. The microscopical method will
      continue to be the gold standard-the best available criterion for the validation
      of our tests-for diagnosis of acute malaria.

PMID- 8273319
TI  - Fat embolism syndrome following long bone fractures.
AB  - During the period August, 1979 to December, 1992, 14 patients with the Fat
      Embolism Syndrome (FES) were admitted to the University Hospital of the West
      Indies (UHWI). Two were females and 12 males, their ages ranging from 18 to 78
      years, with a median age of 23.5 years. All had lower limb long bone fractures.
      Clinical features included fever, tachypnoea, confusion and drowsiness. They were
      all hypoxaemic; 9 required Intensive Care Unit (ICU) admission and, of these, 4
      needed ventilatory support. Five patients became comatose, 4 of whom developed
      decerebrate posturing. There was one death from Klebsiella septicaemia, and 13
      patients recovered fully. The FES is a serious life-threatening complication of
      long bone fractures whether simple or compound, usually occurring within 72 hours
      of the injury. A high index of suspicion is needed for its prompt detection, and
      early attempts at maintaining adequate tissue oxygenation must be instituted if
      serious neurological complications and death are to be avoided.

PMID- 8273320
TI  - Comparison of three bowel preparations for sigmoidoscopy.
AB  - The efficacy of three lower bowel preparations in 96 patients undergoing rigid
      sigmoidoscopy was studied. The maximal length of insertion and clarity of view
      were assessed in each group and compared to patients without bowel preparation.
      Blood per rectum and diarrhoea were the main indications for sigmoidoscopy. The
      maximal insertion of the instrument was similar for all groups and the
      rectosigmoid junction was examined in the majority. The clarity of view was good
      in 71% of patients receiving Fleet enema, 68% of those receiving Dulcolax micro
      enema, 36% in the Dulcolax suppository group and 16% in the group without bowel
      preparation. There were no adverse effects or complications arising from bowel
      preparation or sigmoidoscopy. Bowel preparation significantly improves the number
      of satisfactory sigmoidoscopic examinations, and the use of simple disposable
      enemas is safe and effective.

PMID- 8273321
TI  - A randomized controlled trial of solcoseryl and duoderm in chronic sickle-cell
      ulcers.
AB  - A randomized controlled trial of Solcoseryl, DuoDerm and conventional
      conservative therapy with Eusol has been performed in 32 patients with homozygous
      sickle-cell (SS) disease. After 12 weeks' baseline observation, patients were
      randomized to one of three therapies and monitored for a further 12 weeks. Of 44
      ulcerated legs, 20 received control treatment, 12 Solcoseryl and 12 DuoDerm.
      DuoDerm was generally unacceptable, and two-thirds of the patients defaulted from
      this treatment. Solcoseryl increased ulcer healing compared to the controls but
      the difference was not significant. Solcoseryl was well tolerated and may have a
      role in the treatment of chronic leg ulcers of sickle-cell disease.

PMID- 8273322
TI  - Hysteroscopic assessment of abnormal uterine bleeding in users of the
      intrauterine contraceptive device.
AB  - Sixty users of the IUD who complained of abnormal menstrual blood loss were
      evaluated by hysteroscopy, and the findings were compared with a matched group
      who had this investigation for "missing strings". Submucous fibroids and
      endometritis were more frequent in the study group whereas malposition of the IUD
      was commoner in the controls (p < 0.05).

PMID- 8273323
TI  - Gender stress: a preliminary survey with specific reference to female physicians.
AB  - Practicing female physicians in Trinidad and Tobago were studied to identify
      major causal factors of negative stress. Results indicated that major stressors
      were as follows: job (36%), finance (32%), children (20%), relationships (20%).
      The minor stressors identified were: children (48%), finance (36%), relationships
      (36%), job (32%), and health (20%). The physicians showed the ability to cope
      with the stress and this was attributed to, inter alia, self-sufficiency,
      empowerment, self-fulfillment and gender.

PMID- 8273324
TI  - Hydrops of the gallbladder.
AB  - Hydrops of the gallbladder is an uncommon condition of infants and children.
      There is acute distension of the gallbladder in the absence of calculi without
      evidence of inflammation in the early stages of the disease. A case of hydrops of
      the gallbladder in a 4-year-old male child is presented. The literature is
      reviewed and the diagnosis and treatment of the condition discussed.

PMID- 8273325
TI  - Fibrodysplasia ossificans progressiva. Report of a case in Trinidad and Tobago.
AB  - A case of fibrodysplasia ossificans progressiva is herein reported in a 27-year
      old black woman. This is a very rare condition, the first to be reported from
      Trinidad and Tobago.

PMID- 8273326
TI  - The malaria situation in the Caribbean region.

PMID- 8273327
TI  - Obstetrics and gynaecology--a Caribbean perspective.

PMID- 8273328
TI  - Progress in medical education in the Faculty of Medical Sciences, University of
      the West Indies: implementation of problem-based learning at the St. Augustine
      Campus.
AB  - This paper reviews some of the developmental procedures regarding changes in
      Medical Education within the Faculty of Medical Sciences, University of the West
      Indies. Discussed are some of the constraints experienced in attempting
      curriculum changes in the established Medical School at Mona, Jamaica, as
      compared with the implementation of a Problem-based Learning Strategy curriculum
      at the Eric Williams Medical Complex, St. Augustine, Trinidad and Tobago. At
      Mona, integration of disciplines, Community-health and other programmes were
      attempted. However, it was at the Eric Williams Complex, a new school, that the
      Faculty of Medical Sciences was able to implement a problem-based programme.

PMID- 8273329
TI  - Aging and left ventricular performance.

PMID- 8273330
TI  - Measles epidemic from failure to immunize.
AB  - During 1988 through 1990, California experienced its worst measles epidemic in
      more than a decade, with 16,400 reported cases, 3,390 hospital admissions, and 75
      deaths. More than half of the patients were younger than 5 years; the highest
      incidence was among infants younger than 12 months. The epidemic centered in low
      income Hispanic communities in southern and central California. The major cause
      of the epidemic was low immunization levels among preschool-aged children and
      young adults. Rates of complications, admission to hospital, and death were
      surprisingly high. Outbreak control efforts met with indeterminate success.
      Problems with these efforts included insufficient funding early in the epidemic
      and disappointing public response to community-based immunization campaigns. The
      cost of medical care and outbreak control for the epidemic is conservatively
      estimated at $30.9 million. Unless the level of immunization in preschool-aged
      children is increased, this type of epidemic will probably recur.

PMID- 8273331
TI  - Amnesia in medical practice.
AB  - This discussion was selected from the weekly staff conferences in the Department
      of Medicine, University of California, San Francisco. Taken from a transcription,
      it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine,
      under the direction of Lloyd H. Smith Jr, MD, Professor of Medicine and Associate
      Dean in the School of Medicine.

PMID- 8273333
TI  - Painful snapping hip in young adults.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following inventory of items of progress in orthopedics. Each item, in the
      judgment of a panel of knowledgeable physicians, has recently become reasonably
      firmly established, both as to scientific fact and important clinical
      significance. The items are presented in simple epitome, and an authoritative
      reference, both to the item itself and to the subject as a whole, is generally
      given for those who may be unfamiliar with a particular item. The purpose is to
      assist busy practitioners, students, researchers, and scholars to stay abreast of
      these items of progress in orthopedics that have recently achieved a substantial
      degree of authoritative acceptance, whether in their own field of special
      interest or another. The items of progress listed below were selected by the
      Advisory Panel to the Section on Orthopedics of the California Medical
      Association, and the summaries were prepared under its direction.

PMID- 8273332
TI  - Prognosis after graft replacement operation for abdominal aortic aneurysm.
AB  - We analyze findings on the long-term survival of patients undergoing elective
      graft replacement operations for abdominal aortic aneurysm. We review the
      principal surgical case series published in peer-reviewed, English-language
      journals over the past 15 years. Preoperative mortality was 4.0%, and 5-year
      survival was 69% in 16 reviewed studies encompassing 4,288 patients. Articles on
      late survival have largely focused on the preoperative assessment of coronary
      artery disease in patients who are candidates for aortic resection. The influence
      of other recognized risk factors, such as advanced age, hypertension,
      cerebrovascular disease, congestive heart failure, diabetes mellitus, and
      multiple aneurysms, is often not well specified in these studies. As a greater
      number of older patients with abdominal aortic aneurysm are seen with serious
      associated disease, knowledge about the expected survival of patients with
      surgically treated aneurysms is becoming more important to both primary care
      physicians and vascular surgeons when eliciting patient preferences for surgical
      treatment.

PMID- 8273334
TI  - Meniscal repair.

PMID- 8273335
TI  - Male adolescent idiopathic scoliosis.

PMID- 8273336
TI  - Physical treatment of soft tissue injuries.

PMID- 8273337
TI  - Surgical management of spinal metastases.

PMID- 8273338
TI  - Arthroscopic shoulder treatment--what can and cannot be done.

PMID- 8273339
TI  - Prophylactic antibiotics in total joint arthroplasty.

PMID- 8273340
TI  - Posterior tibial tendon dysfunction.

PMID- 8273341
TI  - Factitious Cushing's disease.

PMID- 8273342
TI  - Isolated pulmonary metastases from prostatic adenocarcinoma.

PMID- 8273343
TI  - Erythroderma associated with ingestion of an herbal product.

PMID- 8273344
TI  - Anatomy of health care reform proposals.
AB  - The current proliferation of proposals for health care reform makes it difficult
      to sort out the differences among plans and the likely outcome of different
      approaches to reform. The current health care system has two basic features. The
      first, enrollment and eligibility functions, includes how people get into the
      system and gain coverage for health care services. We describe 4 models, ranging
      from an individual, voluntary approach to a universal, tax-based model. The
      second, the provision of health care, includes how physician services are
      organized, how they are paid for, what mechanisms are in place for quality
      assurance, and the degree of organization and oversight of the health care
      system. We describe 7 models of the organization component, including the current
      fee-for-service system with no national health budget, managed care, salaried
      providers under a budget, and managed competition with and without a national
      health budget. These 2 components provide the building blocks for health care
      plans, presented as a matrix. We also evaluate several reform proposals by how
      they combine these 2 elements.

PMID- 8273345
TI  - Aging and the heart.

PMID- 8273346
TI  - Surgical decision making--the repair of abdominal aortic aneurysms.

PMID- 8273347
TI  - Timely reporting of AIDS cases.

PMID- 8273348
TI  - Abnormal mammogram after steering wheel injury.

PMID- 8273349
TI  - Complications of do-not-resuscitate orders.

PMID- 8273350
TI  - Complications of do-not-resuscitate orders.

PMID- 8273351
TI  - The potential effects of enterprise liability.

PMID- 8273352
TI  - Cocaine toxicity in glycogen storage disease.

PMID- 8273353
TI  - Advances in cutaneous laser surgery.

PMID- 8273354
TI  - Audible third heart sound.

PMID- 8273355
TI  - Why physicians retire continued.

PMID- 8273356
TI  - Access to obstetric care--the San Diego experience.

PMID- 8273357
TI  - [Prevalence of Borrelia burgdorferi serum antibodies in 651 patients with
      predominantly neurologic diseases].
AB  - An analysis was undertaken to the records of 651 patients (median age 51 years,
      range 1-91; 334 male and 317 female patients), who were admitted for various
      reasons to the department of neurology and psychosomatics of the county hospital
      in Villach (Karnten, Austria), over the period of one year. The clinical
      diagnoses were mostly neurological and psychiatric (n = 599), involving 25
      different conditions. Other diagnoses (n = 52) comprised a group of 13 various
      conditions. Sera of all these patients were tested for antibodies to Borrelia
      burgdorferi. Overall seropositivity was 37.8%. Seropositivity increased
      significantly with age (p < 0.01). Seroprevalence exceeded 40% in patients with
      meningitis, paresis of the cranial nerves, cervical syndrome, pareses and
      sponylitis. The erythrocyte sedimentation rate (ESR) was raised in 37.9% of cases
      which was not related to seropositivity. ESR was significantly increased in
      patients with lumbago (p < 0.01) and with arthritis (p < 0.05). Antibiotics and
      dosages used were recorded in 164 cases. All these cases improved after therapy.
      Of 81 patients with a history of tick bite, 43 (53%) were seropositive. This is a
      significantly higher incidence than that of patients without tick bites (p <
      0.01). The retrospective evaluation of patients' records showed that anamnestic
      and clinical findings alone do not suffice to establish the specific diagnosis of
      Lyme borreliosis and, hence, do not provide the indication of appropriate
      therapy. Furthermore, the mere demonstration of serum antibodies to Borrelia
      burgdorferi does not give information on the current state of infection. In case
      of a suspected Borrelia burgdorferi infection confirmatory tests are
      needed.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273358
TI  - [Effectiveness of relaxation groups in patients with chronic respiratory tract
      diseases].
AB  - In the long-term treatment of patients with chronic respiratory diseases, patient
      education contributes significantly towards improving the effectiveness of
      conventional drugs in the treatment of asthma-specific complaints and anxiety, as
      well as playing a role in improved disease coping. The aim of this study was to
      verify whether relaxation training programs undertaken subsequent to patient
      education may have an additional effect with regard to both medical and
      psychological variables. Relaxation training encompasses the basic exercises of
      autogenics, as well as exercises of functional relaxation. 49 patients
      participated in the relaxation group (22 male, 27 female). The mean age was 50.5
      +/- 16.5 years. The control group used was made up of 37 patients with chronic
      respiratory diseases (17 male, 20 female) who had received asthma education, but
      no further therapeutic intervention. Prior to and immediately after the
      relaxation training, the following investigations were undertaken: lung function,
      patient diary, Spielberger anxiety scale, Giessen list of complaints (modified
      and augmented) and Ziegler coping questionnaire. The linear rating scale model
      was used for measuring changes. The following significant changes were observed
      in the relaxation group as compared with the control group: decrease of trait
      fear, alleviation of asthma-specific complaints and asthma attacks, decrease in
      sleep disturbances and in morning coughing urge, reduction in the required
      quantities of controlled-dosage aerosol, and a modified attitude toward the
      disease in the sense of an improved subjective coping competence.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8273359
TI  - [Infective pathogens as a possible etiology of idiopathic peripheral facial
      paralysis].
AB  - A prospective clinical study was carried out from 1988 until 1990 on 38
      consecutive patients with Bell's palsy at the Neurological Department of
      Innsbruck University Hospital. The age range was between 16 and 88 years, the
      female:male ratio was 18:20. Serological methods were employed to study the
      impact of infectious agents on the aetiology of this disease. 11 out of 38 cases
      (= 29%) were probably infectious in origin, whereby 6 cases were due to Borrelia
      burgdorferi, 4 to Varicella zoster virus (VZV) and 1 to Herpes simplex virus
      (HSV), as determined by elevation of antibody titre or presence of specific IgM.
      Patients with a significant serological finding were treated with ceftriaxon or
      tetracycline for borreliosis or with acyclovir for VZV or HSV infection.
      Altogether, in 36 of the 38 cases a full recovery was seen at the last follow-up
      investigation.

PMID- 8273360
TI  - Primitive neuroectodermal tumor (PNET) extending into the cerebellopontine angle:
      case report.
AB  - The most common primary tumors of the cerebellopontine angle are growths of the
      8th cranial nerve. The occurrence of other tumors in this area is very rare and
      may cause neuroradiological misinterpretation. We report the findings in a 37
      year-old male patient suffering from a primitive neuroectodermal tumor (PNET)
      extending from the latero-basilar cerebellar hemisphere into the cerebellopontine
      angle (CPA) and causing cerebellar dysfunction as well as symptoms of typical
      cerebellopontine angle lesions. Differential diagnosis of tumors found in this
      area is given as well as a histological description of the tumor along with
      immunohistochemical findings and aspects of possible prognostic relevance.

PMID- 8273361
TI  - [Central labeling of sacculo-cochlear neuronal connection].

PMID- 8273362
TI  - [Interferon--a new therapeutic principle].
AB  - Interferons (IFNs) have already been discovered 35 years ago. In the seventies,
      improvements of blood cell- and tissue culture techniques made it possible to
      obtain sufficient material to be used within clinical therapy studies.
      Recombinant DNA technology allowed large scale production of this protein in
      highly purified form and the development of pharmaceutical specialities. These
      preparations have been used for detailed biological characterisation of IFN.
      Beside antiviral activity IFN has potent antitumoral effects (inhibition of
      proliferation, influence on oncogene expression and growth factor production,
      induction of differentiation, inhibition of transformation). Furthermore, IFNs
      are potent immunomodulating agents as they augment cytotoxic activity of effector
      cells, modulate the expression of membrane proteins (tumor-associated antigens,
      histocompatibility antigens) and have influence on the cytokine cascade. Based on
      these pleiotropic activities IFNs can be considered new therapeutics principles.

PMID- 8273363
TI  - [The therapeutic effect of interferon-alpha exemplified by hairy cell leukemia].
AB  - Hairy cell leukemia (HCL) was one of the first malignancies in which therapy with
      natural interferon-alpha achieved complete remissions. In an early multicenter
      trial we could confirm the efficacy of IFN, especially of recombinant
      preparations. In more than 14 clinical studies using all types of IFN-alpha in
      dose ranges of 2.000,000 to 3.000,000 remission rates of 80 to 90% have been
      documented. The observation that interruption of IFN therapy may result in a
      relapse which responds again to IFN implies the need for continuous therapy with
      IFN at a low dose level in patients with HCL. Refractory relapses might respond
      to adenosine-desaminase-inhibitors. Own investigations show that the pancytopenia
      in HCL is a result of a lack of hematopoietic growth factors with a dominance of
      inhibitory factors such as TNF-alpha. Thus IFN therapy does not directly act on
      hairy cells but rather via influences on other cellular regulatory mechanisms.

PMID- 8273364
TI  - [Interferon-alpha therapy in chronic myeloid leukemia].
AB  - In 1983 was for the first time reported that natural interferon-alpha (IFN-alpha)
      has a cytoreductive effect when used for treatment of chronic myelogenic leukemia
      (CML). The following studies using natural as well as recombinant IFN-alpha
      preparations confirmed the high remission rates with this therapy (70% CR and
      more than 30% cytogenetic responses) in patients with CML. Flu-like symptoms are
      recorded in more than 90% of the patients in the initial therapy phase. IFN-alpha
      seems to have no activity in patients in accelerated phase or blast crisis. High
      doses of IFN, i.e. more than 4,000,000 per day, achieve high response rates.
      Responses correlate with risk factors. New possibilities for improvement of
      therapy results with IFN are the combinations of IFN with other therapy
      modalities or concepts such as chemotherapy and/or bone marrow transplantation.

PMID- 8273365
TI  - [Interferon therapy in essential thrombocythemia].
AB  - Interferon-alpha (IFN-alpha) exhibits a clear platelet reductive effect in
      patients with essential thrombocythemia as well as in other chronic
      myeloproliferative disorders with thrombocytosis. In a total of 51 patients with
      chronic myeloproliferative disorders with thrombocytosis we analyzed the effect
      of IFN-alpha in respect to platelet reduction, remission rates, induction- and
      maintenance dosage, long term tolerance and side effects. According to our
      classification CML 6, chronic mega-karyocytic granulocytic myelosis 5, essential
      thrombocythemia 26 and polycythemia vera 15 patients were treated. Treatment
      consisted of induction with 3 or 5 MU IFN-alpha daily followed by a maintenance
      therapy with 3 or 5 MU thrice weekly. Platelet reduction was found in all
      patients, CR (platelets < 450 G/l) in 78%. Within 2 months of induction therapy,
      CR in patients treated with 5 MU IFN daily was found in 75% compared to 52% in
      patients treated with 3 MU IFN daily. Dosage reduction in maintenance periode
      caused an increase of platelets to more than 450 G/l in 39% of patients. Out of
      40 Philadelphia-negative chronic myeloproliferative disorders treated for more
      than 3 months in 10 patients treatment was disrupted after 5 to 18 months because
      of the following side effects: nausea, fatigue, vertigo, fever, headache,
      diarrhea, anorexia, heartburn, hairloss, myalgia, and thrombocytopenia. Due to
      the mutagenic effect of alkylating cytostatics and Radiophosphorus, IFN-alpha
      treatment represents a first line strategy for chronic myeloproliferative
      disorders with thrombocytosis especially in younger patients who are symptomatic
      and in those who suffered from episodes of bleeding or thrombosis.

PMID- 8273366
TI  - [Interferon therapy in multiple myeloma].
AB  - Multiple myeloma is a B-cell malignancy characterised by a clonal expansion of
      plasma cells. Prognosis of the disease can be based upon clinical stage and
      biological features of myeloma cells as well as of their products. Cytostatic
      therapy is a standard in the treatment of multiple myeloma. A new aspect is the
      therapeutic administration of recombinant interferons (rIFNs). Some experience
      has been gathered that chemotherapy-induced remissions (plateau phase) can be
      maintained by IFN-therapy. In induction therapy, IFN in combination with
      cytostatic agents has some therapeutical relevance, either. The administration of
      IFN in the treatment of multiple myeloma represents a new therapeutic strategy.

PMID- 8273367
TI  - [Interferon-alpha therapy in non-Hodgkin's lymphoma].
AB  - Interferon-alpha (IFN-alpha) has besides its known virostatic effects also
      differentiating, immuno-modulating, and antiproliferative effects. According to
      these effects the place of IFN-alpha has been tested for distinct malignant
      diseases. In the treatment of hematologic diseases IFN-alpha has made substantial
      progress in hairy-cell leukemias and for those IFN-alpha is an established
      indication. For other entities of low-grade non-Hodgkin lymphomas (NHL) IFN-alpha
      is an effective drug, remission rates of 46% in average can be achieved. The
      efficiency is dependent from histologic subtype and tumor mass. The remission
      durations mentioned in the literature are variable, however generally not longer
      than with conventional treatments. Recent studies suggest, that IFN-alpha could
      prolong chemotherapy induced remissions.

PMID- 8273368
TI  - [Interferon-alpha in cutaneous T-cell lymphoma].
AB  - There exists a variety of treatment modalities for cutaneous T-cell lymphoma
      (CTCL) which are used according to localization and extension of the disease.
      Additionally, in the last years it has been demonstrated by several groups that
      interferon-alpha (IFN-alpha) therapy dependent on stage of the disease results in
      response rates of 40 to 50%. We could demonstrate that the combination of low
      dose IFN with retinoids is able to induce long term remissions with low incidence
      of side effects. Other combinations of IFN-alpha with standard therapies and/or
      experimental therapies (Pentostatin) seem to contribute-according to preliminary
      data-to an improvement of remission rates in CTCL.

PMID- 8273369
TI  - [Interferon therapy in malignant melanoma].
AB  - The incidence of malignant melanoma in the Caucasian population is rising
      constantly. As mortality rate, also morbidity rate is elevated. Because of better
      diagnostic tools the curability in early stages is enlarged quantitatively. For
      high risk cases in stage I and II and metastatic disease there exists no
      established therapy regimen. Longtime Interferon-alpha therapy as an adjuvant
      therapeutic tool had shown an improvement of relapse-free interval and survival.
      The combination of chemotherapeutic regimen and Interferon in the interval
      resulted in an increase up to 20% success risk.

PMID- 8273370
TI  - [Interferon-alpha therapy in hypernephroma].
AB  - The prognosis of metastatic renal cell cancer is unfavourable as neither chemo-,
      radiation- nor hormonal therapy achieve tumor remissions in more than 10% of the
      patients. Several methods of immunotherapy so far employed have not led to
      improved treatment results. However, with interferon (IFN) therapy--dependent on
      different prognostic factors--remissions in the range form 15 to 40% have been
      documented. The combination of IFN-alpha with vinblastine seems, according to
      some studies, to increase response rates. There is evidence that IFN-alpha in
      combination with IFN-gamma or interleukin-2 is more effective than monotherapy.
      New treatment possibilities are the combination of IFN with 5-fluorouracil or new
      cytokines.

PMID- 8273371
TI  - [Locoregional interferon therapy in urology].
AB  - Review of loco-regional application of interferon (IFN) in the treatment of
      urological tumors. Only in the recurrence prophylaxis of superficial bladder
      cancer promising results of phase II studies are available. So an ongoing study
      of the Austrian Urology Oncology group (AUO). In general locoregional IFN
      application in the treatment of urological tumors should be restricted to
      clinical trials.

PMID- 8273372
TI  - [Therapy of chronic hepatitis B with interferon].
AB  - Over the last decade several well conducted studies in Europe and North America
      have shown that recombinant interferon-alpha (IFN-alpha) is an effective drug for
      the treatment of chronic hepatitis B. 5 million units given subcutaneously daily
      or every other day for 4 to 6 months will achieve remission in 30% (complete with
      loss of all viral markers) to 40% (incomplete with resolution of hepatitis but
      persistence of viral markers) of patients. High activity of hepatitis and low
      rate of viral replication are favourable prognostic markers. Male sex, infection
      in childhood and superinfection with the delta virus are associated with a low
      response rate. Cirrhotics in particular in the decompensated state of disease
      should be treated in a center with the possibility of liver transplantation.

PMID- 8273373
TI  - [Interferon therapy in hepatitis C].
AB  - Chronic hepatitis C is one of the major causes of liver cirrhosis and seems to
      play a role in the pathogenesis of primary liver cancer. So far, no effective
      therapy--with the exception of some antiviral agents--was available for this
      disease. Interferon-alpha (IFN-alpha) therapy results in about half of patients
      in a normalisation of liver transaminases within 4 weeks. Placebo-controlled
      studies confirm that in about 40% of patients IFN therapy achieves complete
      remissions. Frequently termination of IFN therapy is followed by a relapse.
      Therefore higher IFN doses and longer and/or repeated therapy cycles are
      currently investigated in order to improve treatment results. Furthermore, IFN
      alpha is combined with other therapeutic principles. The possible usefulness of
      IFN-alpha for treatment of acute hepatitis C is under investigation.

PMID- 8273374
TI  - [Interferon in anogenital infections with human papillomavirus].
AB  - Interferons (IFN) provide a systemic alternative for the therapy of human
      papillomavirus (HPV) induced anogenital warts. Local therapy cannot totally
      eliminate latent viral genome in the perilesional epithelium. This causes the
      danger of new exacerbations. Reviewing different reports and by own therapeutic
      experience we think, that IFN treatment may be successful in combination with
      local therapy and for pre-surgical diminution of extended condyloma. Sufficient
      dose is necessary. Poor effects are to be expected if the warts lasted for longer
      than 12 months and in case of severe immunodeficiency.

PMID- 8273375
TI  - WHO Expert Committee on drug dependence.

PMID- 8273376
TI  - Emergency surgical treatment for bleeding duodenal ulcer: oversewing plus
      vagotomy versus gastric resection, a controlled randomized trial. French
      Associations for Surgical Research.
AB  - The best surgical procedure to treat bleeding bulbar peptic ulcer is unknown. The
      rates of postoperative bleeding recurrence, duodenal leakage, and mortality were
      compared in patients undergoing oversewing plus vagotomy (O+V) or gastric
      resection (GR) with ulcer excision. Of 202 patients undergoing emergency surgery
      for massive, persistent, or recurrent bleeding from bulbar peptic ulcer, 120
      patients were enrolled in a prospective randomized trial. Fifty-nine were
      assigned to O+V and 61 to GR. One patient in each group was excluded after
      randomization. The two groups were well matched with respect to clinical and
      prognostic factors. The rate of postoperative bleeding recurrence was 17% after
      O+V and 3% after GR (p < 0.05). The duodenal leak rate was higher after GR than
      after O+V (13% vs. 3%) (p < 0.10) but was not different when the morbidity of
      reoperations for bleeding recurrence after O+V was considered on an "intention to
      treat" basis (12% vs. 13%). Overall postoperative mortality was similar: 22%
      (O+V) versus 23% (GR). Sixteen deaths were unrelated to the surgical procedure
      itself. Of 82 nonrandomized patients, 10 were not analyzed. In the 72 other
      nonrandomized patients, bleeding recurrence, duodenal leakage, and postoperative
      mortality rates were consistent with the results of the controlled trial, as they
      were 29% (O+V 32%; GR 0.7%), 16% (O+V 0.7%; GR 26%) and 27% (O+V 18%; GR 33.3%),
      respectively. We conclude that GR with ulcer excision is the procedure of choice
      for the emergency surgical treatment of bleeding duodenal ulcer because
      postoperative bleeding recurrence is lower, and the overall rates of mortality
      and duodenal leakage are the same as with O+V.

PMID- 8273377
TI  - Correlation of metabolic acidosis with outcome following injury and its value as
      a scoring tool.
AB  - This study looked at preresuscitation arterial pH as a predictor of outcome in
      injury. Seriously injured patients admitted to the Trauma Service over a 5-month
      period were evaluated prospectively. Data collected included basic patient
      demographics, initial arterial blood gas determinations (ABGs) including pH,
      bicarbonate (HCO3), base deficit or excess (BASE), admitting trauma score (TS),
      discharge injury severity score (ISS), total blood products used for initial
      resuscitation (TBP), and outcome. There were 191 patients averaging 34.7 years
      old with average TS 13.6, ISS 19.5, initial pH 7.38 +/- 0.09, HCO3 20.9 +/- 4.0,
      and BASE -3.3 +/- 4.7. The average TBP was 1309 cc, and overall mortality was
      13/191 (6.8%). Comparing survivors to nonsurvivors, the ISS (18.2 vs. 38.3), TS
      (14.1 vs. 7.8), TBP (976 vs. 5881 cc), HCO3 (21.1 vs. 17.6), and BASE (-3.1 vs. 
      5.8) data were significantly different; pH (7.38 vs. 7.36) and age (34.4 vs.
      38.5) were not. Using multiple regression with TBP as the dependent variable,
      BASE, age, TS, and to a lesser extent pH and HCO3 correlated (r = 0.536; p <
      0.001); using outcome as the dependent variable, only TS and age correlated (r =
      0.465; p < 0.0001). Although metabolic acidosis (pH, HCO3, BASE) predicts the TBP
      used, it does not improve on TS and age for predicting outcome.

PMID- 8273378
TI  - Role of parenteral nutrition in preventing malnutrition and decreasing bacterial
      translocation to liver in obstructive jaundice.
AB  - Surgery in patients with obstructive jaundice is associated with significant
      infectious complications probably due to impaired immune function and
      malnutrition. Total parenteral nutrition (TPN) may alleviate malnutrition but may
      also promote bacterial translocation (BT) from the gut. To elucidate if TPN can
      prevent malnutrition without promotion of BT in obstructive jaundice, 40 dogs
      underwent laparotomy for tissue sampling and placement of a central venous line
      and were allocated into one of four groups: I (PO-control) received dog chow and
      water ad libitum; II (PO-CBDL) underwent ligation of common bile duct (CBDL) and
      was fed dog chow; III (TPN-control) received TPN; and IV (TPN-CBDL) underwent
      CBDL and received TPN. Body weight, blood samples for liver function tests and
      bacterial culture, and tissues from liver and mesenteric lymph nodes (MLN) for
      quantitative bacterial culture and for histology were obtained prior to and 2
      weeks after the experiment. The incidence of BT to MLN was 40% in the PO-CBDL and
      TPN-CBDL animals, which was significantly different from the other two groups
      (0%; p < 0.05). The incidence of BT to liver was 70% (7/10) in the PO-CBDL
      animals, which was significantly higher than that in groups I, III, and IV (0%,
      20%, 20%, respectively) (p < 0.05). The PO-CBDL animals showed a significant
      decrease in body weight and prealbumin compatible with malnutrition, whereas the
      TPN-CBDL animals showed a significant increase in alkaline phosphatase and a
      consistent cholestasis on histology. The data suggest that TPN can prevent
      jaundice-associated malnutrition and decrease BT to liver but should be
      administered cautiously because it may precipitate cholestasis.

PMID- 8273379
TI  - Refundoplication for recurrent gastroesophageal reflux.
AB  - Reoperation after a failed antireflux procedure is a surgical challenge. Many
      operative techniques have been proposed, but reports on systematic follow-up with
      endoscopy and esophageal function tests are few. The purpose of the present study
      was to evaluate the results of repeated fundoplication in cases of recurrent
      reflux, including assessment of esophageal function. Of the 18 cases of repeat
      fundoplication performed for recurrent reflux during 1970-1991 at Tampere
      University Hospital, 15 were evaluated a median of 18 (range 5-152) months after
      reoperation. Follow-up studies included endoscopy in all and esophageal function
      tests (esophageal 24-hour pH recording, manometry, and radionuclide transit) in
      14 cases. All the patients had defective fundic wrap before reoperation, whereas
      at follow-up 12 of the 15 wraps were intact. Reflux symptoms were diminished in
      all 15. Six patients (40%), however, had objective recurrence of reflux
      (esophagitis or pathologic pH recording). Three of the recurrences were due to
      slipped fundic wrap, but the others were probably caused by impaired esophageal
      function. By repeat fundoplication the wrap could be repaired as reliably as in
      primary operation. Symptomatic outcome and objective results were reasonable. The
      results were, however, not as good as after primary operation, which was due to
      more impaired esophageal motility caused by prolonged reflux or repeated surgery
      (or both).

PMID- 8273380
TI  - Evaluation of "gastric" emptying time in the J pouch compared with a standard
      esophagojejunal anastomosis.
AB  - Gastric emptying times and symptoms were recorded in 18 patients after total
      gastrectomy and either a 15-cm J-pouch (n = 10) or a standard esophagojejunal
      anastomosis (n = 8). A solid test meal labeled with 99mTc was used to compare the
      emptying times. The postoperative symptoms and nutritional status were also
      assessed. The J-pouch resulted in a prolonged period of food retention in the
      upper jejunum (p < 0.02) compared to that with a standard esophagojejunal
      anastomosis. The patients with a J-pouch had fewer episodes of postprandial pain
      (p < 0.03) or vomiting (< 0.04). They also had fewer dietary restrictions (p <
      0.04) and better nutritional status.

PMID- 8273381
TI  - Endocrine-metabolic response to abdominal aortic surgery: a randomized trial of
      general anesthesia versus general plus epidural anesthesia.
AB  - The influence of epidural anesthesia on the endocrine-metabolic response
      following abdominal aortic reconstruction was studied in a prospective randomized
      trial. Cortisol and catecholamine responses and nitrogen balance were measured in
      two groups of five patients receiving general anesthesia only (group 1) or
      general anesthesia combined with epidural bupivacaine (group 2). The study lasted
      from preoperatively until the first postoperative day. At 2100 hours on the day
      of surgery serum cortisol concentrations were higher in group 1 than in group 2
      (1.41 versus 0.82 mumol/L; p < 0.01). Likewise the total perioperative
      hypercortisolemia, expressed as the area under the curve, was significantly
      higher in group 1 (11.7 versus 5.7 mumol/L/hr, p < 0.01). Intraoperative urinary
      excretion of epinephrine and postoperative norepinephrine excretion were
      significantly higher in group 1 than in group 2. Urinary excretion of free
      cortisol and cumulative nitrogen balance were not different between the groups.
      Although the number of patients was limited and the sensory nerve block level was
      not measured perioperatively, this study suggests that epidural anesthesia
      attenuates the stress response to aortic surgery.

PMID- 8273382
TI  - Expression of a potential metastasis suppressor gene (nm23) in thyroid neoplasms.
AB  - Identification of multiple clinical and pathologic prognostic factors in
      differentiated thyroid cancer has permitted some degree of risk stratification.
      However, these clinical indices fail to distinguish potential intrinsic
      differences in tumor virulence. The nm23 gene has been identified as a potential
      metastasis suppressor gene that is homologous to nucleoside diphosphate kinases.
      Studies in human breast cancer have shown a significant inverse correlation
      between nm23 levels and nodal involvement/tumor recurrence. Given the possible
      clinical utility of a marker of metastatic potential in the management of thyroid
      carcinoma, we examined 34 thyroid neoplasms and a human medullary thyroid cancer
      (MTC) cell line (TT) for nm23 expression. Normalized nm23 expression was assessed
      by Northern analysis of tumor RNA. nm23 Expression (tumor expression/TT cell
      expression, mean +/- SE) was 1.14 +/- 0.15* in MTCs (n = 5), 0.70 +/- 0.10* in
      follicular cancers (n = 6), 0.51 +/- 0.11 in papillary cancers (n = 19), and 0.31
      +/- 0.03 in follicular adenomas (n = 4) (*p < 0.05 when compared to adenomas).
      Within histologic groups, we found no correlation between nm23 expression and
      nodal involvement of distant metastases. Our results indicate that thyroid
      neoplasms of different histologies express varying levels of the nm23 transcript.
      Although nm23 expression seems diminished in metastatic breast cancer, it appears
      not to be the case in metastatic thyroid cancer. The nm23 gene may therefore have
      different roles in the evolution and metastases of different neoplasms.

PMID- 8273384
TI  - Transplantation of human cryopreserved adenomatous and hyperplastic parathyroid
      tissue to the hypocalcemic nude mouse.
AB  - Cryopreserved parathyroid glands from patients operated on for
      hyperparathyroidism were stored for further auto- or allografting. In an attempt
      to better use cryopreserved parathyroid glands in humans, we designed a study
      whose goal was to compare human parathormone (hPTH) secretion from cryopreserved
      parathyroid glands with regard to tissue histology (adenoma or hyperplasia),
      mass, and time of storage in hypocalcemic Nude mice and to be able to better use
      them in humans. A new hypocalcemic experimental model, using parathyroidectomized
      Nude mice was set up. Hypocalcemic mice received calibrated grafts from human
      parathyroid glands cryopreserved between 1982 and 1992 originating from 30
      patients (15 adenomas, 15 hyperplasias). Each parathyroid was grafted into two
      mice under the ratio of one mass-unit (12 mg) and three mass-units (36 mg). The
      hPTH concentration was assessed by an immunoradiometric method 21 days after
      grafting. The mean cryopreservation time was 677 days (54-3187 days). The time of
      cryopreservation was identical in the two kinds of tissue (p = 0.88). The hPTH
      concentration in 59 living mice was 72.2 +/- 271.4 (SD) ng/ml (3-1936 ng/ml).
      This concentration was 7.1 +/- 4.3 ng/L for adenomas versus 139.4 +/- 378.6 ng/L
      for hyperplasias (p = 0.003) and 87.1 +/- 352.6 ng/L for one-unit-mass grafts
      versus 56.7 +/- 152.5 ng/L for three unit-mass grafts (p = 0.824). Hyperplastic
      glands showed more secretion, which was confirmed in both mass related groups (p
      = 0.02, p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273383
TI  - Amiodarone-induced thyrotoxicosis: is there a place for surgery?
AB  - Amiodarone-induced hyperthyroidism has on most instances been reported as mild,
      and thyroid functions return to normal after discontinuation of the drug.
      Nevertheless, life-threatening amiodarone-induced thyrotoxicosis has also been
      described. Conventional treatments such as antithyroid drugs (thionamide) and
      corticosteroids are essentially ineffective or fail to alter the dramatic course
      of the thyroid crisis. This limited effectiveness of medical therapy,
      particularly in patients with previously neglected or unknown thyroid disease,
      prompted us to intervene surgically. We report a series of nine patients who
      underwent total or near-total thyroidectomy as a first-line therapy for five of
      them. Surgery resulted in rapid resolution of thyrotoxicosis with an uneventful
      postoperative course. This approach has the advantage of immediate effectivity,
      low risk of relapse, and appears to be the only treatment that permits continued
      therapy with amiodarone when the drug appears needed to control a life
      threatening arrhythmia.

PMID- 8273385
TI  - Incidentalomas of the adrenal gland: 36 operated patients and review of
      literature.
AB  - Incidental discovery of an adrenal mass during radiologic examinations is common.
      Several recommendations have been made for the management of so-called
      incidentalomas. It has become clear that not all incidentalomas should be
      operated, but the criteria for nonoperative treatment have been under continuous
      debate. In this study 36 operated incidentalomas are presented, and the
      indications for operative treatment are discussed with a review of the recent
      literature on the subject. Four pheochromocytomas and three hormonally active
      cortical adenomas, two producing cortisol and one androgens, were found. In this
      series there were no malignancies. The operation could have been avoided in most
      cases, and patients could have been followed up with repeated radiologic
      examinations. It is suggested that masses smaller than 6 cm in diameter be
      followed radiologically after 3, 9, and 18 months. Masses between 3 and 6 cm
      could be further examined using magnetic resonance imaging and fine needle
      aspiration and then operated if features suggestive of malignancy are found.
      Masses larger than 6 cm in diameter should be treated operatively.

PMID- 8273386
TI  - Operative ultrasonography during hepatobiliary and pancreatic surgery.
AB  - On the basis of our experience with operative ultrasonography during
      hepatobiliary and pancreatic surgery, its indications, benefits, and
      disadvantages are summarized. High-resolution operative ultrasound scanning of
      the liver, biliary tract, and pancreas was performed during 357, 735, and 242
      operations, respectively. The benefits of operative ultrasonography were
      categorized as acquisition of diagnostic information otherwise not available,
      replacement for or complement to operative radiography, and guidance of surgical
      procedures. Operative ultrasonography provided beneficial information during 73
      of 82 hepatic operations (89.0%), 57 of 69 noncalculous biliary operations
      (82.6%), and 177 of 242 pancreatic operations (73.1%). Operative ultrasonography
      was significantly superior (sensitivity 93.3%) to other screening tests for
      diagnosing liver metastasis from colorectal carcinoma evaluated in 189 patients,
      and it detected previously unrecognized metastatic tumors in 18 patients (9.5%).
      For screening common bile duct calculi during 666 operations, operative
      ultrasonography and operative cholangiography were comparable in all indices of
      accuracy except for a higher predictability of a positive test of operative
      ultrasonography (94.8% versus 71.7%). For diagnosing portal vein invasion of
      pancreatic carcinoma, operative ultrasonography provided better overall accuracy
      than preoperative studies (89.7% versus 64.1%). On the basis of operative
      ultrasound findings, previously planned surgical procedures were altered in 32 of
      82 hepatic operations (39.0%) and 24 of 145 pancreatic operations for chronic
      pancreatitis (16.6%). Operative ultrasound guidance of various surgical
      procedures was performed during 88 hepatic and 84 pancreatic operations,
      including 40 ultrasound-guided hepatectomies and 42 pancreatotomies. Operative
      ultrasonography has a number of advantages, such as safety and speed in
      performance, wide application, high diagnostic accuracy, and ability of guiding
      procedures. Its disadvantages are the limitation of the fields of view in certain
      applications, the need for special equipment, and a slow learning curve.

PMID- 8273387
TI  - Role of extracorporeal shock wave lithotripsy in hepato-biliary-pancreatic
      surgery.
AB  - Since the early 1980s extracorporeal shock wave lithotripsy (ESWL) has partially
      replaced major operative procedures in various fields of surgery. In the interest
      of the patient, it is important to determine the exact role of ESWL in surgery.
      Comparing our own prospectively followed patients with other patient series, we
      have tried to assess this role. We treated 133 patients with cholecystolithiasis,
      80 patients with choledocholithiasis, and 17 patients with pancreatic stones
      using a second-generation lithotriptor, the Siemens Lithostar (Siemens, Erlangen,
      Germany). The results suggest a limited role of ESWL for cholecystolithiasis, in
      which it is reserved for patients with high operative risk and patients who
      reject an operation. For choledocholithiasis ESWL seems to become an integral
      part of the treatment in the elderly patient in whom endoscopic stone removal
      proved impossible. Finally, ESWL could become a first option for the treatment of
      intractable pain in patients with chronic calcifying pancreatitis.

PMID- 8273388
TI  - Clinicopathologic factors influencing survival of patients with bile duct
      carcinoma: multivariate statistical analysis.
AB  - To evaluate the influence of various clinicopathologic factors on survival, a
      computer analysis was performed on 70 patients who underwent resection for bile
      duct carcinoma. Univariate analysis of overall survival involving all the
      patients identified 10 factors that were associated with a significant outcome:
      location of primary lesion (p = 0.01), pancreatic invasion (p = 0.004), duodenal
      invasion (p = 0.005), macroscopic and microscopic vascular involvement (p = 0.009
      and p = 0.04), perineural invasion (p = 0.02), lymphatic vessel involvement (p =
      0.04), lymph node metastasis (p = 0.02), histologic type (p = 0.02), and depth of
      cancer invasion (p = 0.04). However, when the interactive effects of these
      factors were taken into account, the pancreatic invasion and perineural invasion
      were selected as the two most significant prognostic factors in a multivariate
      analysis using the Cox stepwise proportional hazards model. The age, sex, size of
      the tumor, macroscopic type of lesions, hepatic infiltration, serosal invasion,
      resected surgical margin at the proximal and distal ends, exposed surgical
      margin, peritoneal dissemination, and hepatic metastasis were not significantly
      associated with prognosis.

PMID- 8273389
TI  - Redo hepatic resection for metastatic colorectal carcinoma.
AB  - Redo hepatic resection for recurrent colorectal metastasis was performed in eight
      patients. There was no operative mortality; major morbidity occurred in 25% and
      minor morbidity in 13% of patients. Four patients are alive and disease-free at
      9, 23, 39, and 49 months, respectively, after their repeat hepatic resection.
      Four patients have died of recurrent disease, with a median time to recurrence of
      6 months and median survival of 15 months. Patterns of failure include hepatic
      failure alone in two patients and pulmonary and hepatic failure in two. Repeat
      liver resection can be performed safely and may be beneficial in some patients
      with recurrent metastases confined to the liver after previous hepatic
      metastasectomy.

PMID- 8273390
TI  - Operative results in 143 patients with hepatocellular carcinoma.
AB  - A total of 143 patients who underwent hepatic resection for hepatocellular
      carcinoma in our department were reviewed. The review was conducted for two
      periods: 1970-1982 (early period) and 1983-1990 (late period), that is, the
      periods before and after introduction of the hepatic surgical technique involving
      the use of a microwave tissue coagulator and ultrasonic dissector. One patient
      underwent extended lobectomy, 12 lobectomy, 9 segmentectomy, and 26 partial
      hepatectomy during the early period. Two patients underwent extended lobectomy, 7
      lobectomy, 9 segmentectomy, 36 subsegmentectomy, and 41 partial hepatectomy
      during the late period. Operative mortality and hospital mortality were 16.7% and
      22.9% during the early period and 1.1% and 8.4% during the late period,
      respectively. The overall mortality rate was significantly lower during the late
      period than during the early period. Postoperative complications developed in
      62.5% of the patients with hepatic resection during the early period and in 48.4%
      of the patients during the late period. The size of tumors during the early
      period was significantly greater than that during the late period. Intraoperative
      blood loss during the late period was significantly lower than that during the
      early period. The survival curve was better among patients who underwent hepatic
      resection during the late period than among those during the early period. The
      satisfactory results during the late period are due to the introduction of
      intraoperative ultrasonography, microwave tissue coagulation, and ultrasonic
      dissection for hepatic surgery.

PMID- 8273391
TI  - Orthotopic liver transplantation in the presence of partial or total portal vein
      thrombosis: problems in diagnosis and management.
AB  - From January 1989 to May 1992, 70 orthotopic liver transplantations (OLT) were
      performed in 69 patients, 53 of whom had cirrhosis (77%). Eleven patients (16%)
      had preoperative partial or total portal vein thrombosis (PVT). Ten of these
      patients had cirrhosis of various causes. PVT was total in three cases and
      partial in eight. Total PVT was detected preoperatively in all three cases. By
      contrast, partial PVT was diagnosed preoperatively in only three of the eight
      cases. In the five other cases of partial PVT, the obstruction was discovered
      intraoperatively during dissection of the portal vein. Surgical management of PVT
      consisted of phlebothrombectomy in ten cases followed by usual end-to-end portal
      anastomosis in nine cases and anastomosis of the graft's portal vein to the
      splenomesenteric confluence in one case. Atypical anastomosis of the graft's
      portal vein to a dilated choledocal vein was performed in one case of total PVT.
      There were no deaths or complications related to the presence of preoperative PVT
      or to its management. One patient died postoperatively of primary graft
      nonfunction at day 5. One patient had arterial thrombosis 3 months after OLT and
      was successfully retransplanted. Two patients died of recurrent carcinoma 3 and 7
      months after OLT. Eight patients are alive 4 to 39 months after OLT. We conclude
      from this series that (1) the prevalence of preoperative PVT among patients
      transplanted for advanced cirrhosis may be high (19% of the cirrhotics in this
      series); (2) PVT is often partial and so difficult to diagnose preoperatively;
      (3) PVT, even when total, can be managed successfully during surgery and does not
      seem to affect survival.

PMID- 8273392
TI  - Electrorectography in chronic proctitis.
AB  - Rectal electrical activity, measured by electrorectography (ERG), was studied in
      18 patients with chronic proctitis (11 ulcerative and 7 bilharzial proctitis).
      Mean age was 36.6 +/- 9.4 (SD) years. Eight healthy volunteers were included as
      controls. Monopolar recordings were made from silver-silver chloride electrodes
      situated 1 cm from the tip of the catheter, which was applied to the rectal
      mucosa. Signals from the electrode were displayed on a U-V recorder. Rectal neck
      and rectal pressures were recorded simultaneously. Pacesetter potentials (PP)
      were also recorded from all subjects. The healthy volunteers had a mean frequency
      of 2.6 +/- 0.6 cycles per minute (cpm), an amplitude of 2.4 +/- 0.5 mV, and a
      velocity of 4.3 +/- 0.5 cm/sec. The potentials had the same frequency and regular
      rhythm when the test was repeated and were followed randomly by bursts of action
      potentials (AP). The rectal pressure increased simultaneously with the AP. In the
      proctitis patients the PP frequency was higher than normal (mean 8.2 +/- 1.6 cpm
      in patients with bilharziasis and 8.9 +/- 2.1 cpm in those with ulcerative
      proctitis) (p < 0.001), whereas the amplitude and velocity were lower than normal
      (p < 0.05 and p < 0.01, respectively). APs had higher frequency and amplitude and
      were accompanied by higher rectal pressure than in the normal volunteers. The
      increased PP, or tachyrectia, may be due to rectal wall or rectosigmoid pacemaker
      irritation caused by proctitis, whereas the diminished amplitude and velocity may
      be caused by a diseased rectal wall. The increased AP frequency and amplitude
      seem to cause increased rectal contractile activity with a resulting
      tenesmus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273393
TI  - Paracolostomal hernia: repair with use of a Dacron prosthesis.
AB  - Several surgical procedures have been described for the repair of paracolostomal
      hernia. We describe a local technique approach using stoma relocation with
      insertion of a Dacron prosthesis. Among 14 patients operated on for
      paracolostomal hernia, this technique was used in 10 patients. There was no
      mortality or morbidity (no prosthesis infection). During follow-up there was one
      recurrence, which was reoperated with a good final result. This technique can be
      recommended for the few patients in whom a surgical repair is mandated.

PMID- 8273394
TI  - A new technique of "Marlex peritoneal sandwich" in the repair of large incisional
      hernias.

PMID- 8273395
TI  - Laparoscopic urology: past, present, and future.

PMID- 8273396
TI  - Carcinoid tumors of the small intestine are uncommon, indolent, slow growing,
      slow metastasizing, neuroendocrine lesions.

PMID- 8273397
TI  - Routine versus selective intra-operative cholangiography during laparoscopic
      cholecystectomy.

PMID- 8273398
TI  - [Immunization with partner lymphocytes: improvement of pregnancy rate in
      sterility patients].
AB  - In a two-centre prospective study 20 patients with a history of unsuccessful
      sterility treatment underwent immunization with paternal lymphocytes to improve
      the pregnancy rate in the subsequent therapeutic AIH or IVF/ET cycle.
      Unsuccessful sterility treatment was defined as no pregnancy after 8 properly
      monitored AIH cycles and at least one diagnostic IVF/ET or more than 3 IVF with
      transfer of 3 embryos. After successful immunization expressed by the induction
      of Fc-receptor blocking antibodies 10/20 patients became pregnant. Nine of these
      patients delivered healthy children, one patient experienced a first trimester
      abortion. A successful second pregnancy occurred in 6 of these patients. No
      significant correlation between the previous history and pregnancy success could
      be found, except a slight advantage for patients with a history other than tubal
      sterility. There were no differences in the anamnestic data as well as in the
      success rate between the two independent centres Gottingen and Leuven (10
      patients each). These data suggest, that adjuvant immunotherapy might improve
      markedly the pregnancy rates in selected cases of sterility.

PMID- 8273399
TI  - [L-carnitine-betamethasone combination therapy versus betamethasone therapy alone
      in prevention of respiratory distress syndrome].
AB  - In this prospective randomised study the effects of antenatal treatment with a
      low dose betamethasone (2 mg/1 day)-L-carnitine (4 g/5 days) combination were
      compared with those of a high dose betamethasone, given alone (8 mg/2 days) on
      the prevention of respiratory distress syndrome (RDS) and mortality in preterm
      infants. One-hundred women entering the trial gave birth to 109 liveborn infants,
      55 in the betamethasone group (A), 54 in the betamethasone-L-carnitine
      combination group (B). Eight of the 55 (14.5%) infants in group A developed RDS,
      four of the 54 (7.3%) in group B, which was significantly more (p < 0.05),
      although in group B the betamethasone dose was dramatically reduced. The
      mortality also was significantly lower after treatment with a betamethasone-L
      carnitine combination compared to betamethasone alone (4 of 55 infants or 7.3% in
      group A versus 1 of 54 infants or 1.8% in group B, p < 0.05). The present results
      demonstrate that in combination with L-carnitine, the betamethasone dose is
      markedly reducible with a concomitant significant reduction of the incidence of
      RDS and mortality of premature newborns.

PMID- 8273400
TI  - [Normal values of color Doppler ultrasound in pregnancy].
AB  - In addition to the flowmetrie of aorta fetalis and a. umbilicalis, color flow
      mapping enables the examination of the renal and middle cerebral arteries in the
      assessment of the fetal blood circulation. The resistance and pulsatility-indices
      of aorta fetalis, umbilical artery, renal artery and middle cerebral artery were
      calculated in a prospective examination of a normal study group of 123 pregnant
      women. Moreover, ratios were established from the pulsatility-indices of renal
      artery and aorta fetalis, renal artery and umbilical artery, middle cerebral
      artery and aorta fetalis, middle cerebral artery and umbilical artery. By the use
      of these ratios, we hope to detect more reliably changes in the fetal blood
      circulation.

PMID- 8273401
TI  - [The value of Doppler ultrasound studies in threatened premature labor].
AB  - 95 patients were investigated using Doppler ultrasound to evaluate its usefulness
      during the clinical management of patients with preterm labor, preterm rupture of
      membranes and incompetent cervix. Cases with additional pregnancy complications
      as preeclampsia or intrauterine growth retardation or infection of the amnion or
      the birth canal were excluded from our study. We examined the umbilical artery
      and the uterine arteries. Predicting preterm birth we found a sensitivity of
      31.4% and a specificity of 70% for the former and a sensitivity of 34.3% and a
      specificity of 83.3% for the latter. As a result of our investigation we have to
      conclude that Doppler ultrasound is not able to predict sufficiently reliable
      preterm birth to use it in clinical management. Normal uterine blood flow in
      cases with preterm labor seems to indicate birth at term in a high degree.

PMID- 8273402
TI  - [Postpartum neonatal weight increase in relation to the course of pregnancy
      (retrospective study of 791 newborn infants)].
AB  - In a retrospective pilot study the weight development of 791 neonates in the
      first five postpartal days was related to clinical and social data relevant for
      the course of pregnancy. I. Pregnancy Course 1. For a variety of reasons,
      neonates of mothers hospitalized for more than two weeks during pregnancy had
      regained their birthweight by the 5th postpartal day significantly less often
      than infants of non-hospitalized women (7% versus 27%). 2. In newborns whose
      mothers had suffered from hyperemesis gravidarum weight loss in the first five
      postpartal days was seen twice as often as in the rest of the group (67% versus
      33%). 3. Postpartal weight loss of infants from gestotic mothers tended to be
      higher and of longer duration compared to the remainder of the group. 4. The same
      phenomenon was seen in diabetic pregnancies. 5. Neonates from smoking mothers had
      a significantly lower postpartal weight loss and had regained their birthweight
      by the 5th postpartal day much more often (35% versus 23). II. Social data 1.
      Newborns from mothers aged up to 18 years reached their birthweight by the 5th
      postpartal day only half as often as infants whose mothers were aged between 18
      and 35 (13% versus 26%). Even if preterm babies were excluded, this trend
      remained. 2. Distinct postpartal weight loss occurred much more often in infants
      of multiparous mothers (3 and more children) compared to the rest of the study
      group (29% versus 18%). 3. Somewhat surprisingly, newborns of mothers from
      islamic countries regained their birthweight earlier than neonates of German
      mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273403
TI  - [Intracerebral subdural hematoma after delivery with peridural catheter
      anesthesia].
AB  - 26 days past an obstetric catheter epidural anesthesia a subdural haematoma right
      fronto-temporal was diagnosed and relieved by operation in a primipara of 19
      years of age. Already several days after the delivery the patient was suffering
      recurrent headaches, at first misinterpreted as post-spinal headaches. Weeks
      later a cranial computer tomography lead to the right diagnosis. Although the
      occurrence of a subdural haematoma after catheter epidural anesthesia is
      extremely rare, untypical headaches following spinal, epidural or caudal
      procedures, should call your attention towards this complication. Because of the
      pressing mechanisms during childbearing, delivering mothers run the risk of a
      subdural haematoma.

PMID- 8273405
TI  - [Abstracts from the fall meeting of the German Association for Heart and
      Circulation Research. Aachen, 23-25 September 1993].

PMID- 8273404
TI  - [Obstetrical management in maternal tuberous sclerosis (Pringle-Bourneville
      syndrome)--a case report].
AB  - The rupture of visceral hamartomas in tuberous sclerosis (Pringle-Bourneville) is
      more likely in pregnancy because of the increased blood volume and can be
      followed by lifethreatening retroperitoneal hemorrhage. To avoid complications
      during delivery the vacuum extraction in epidural anesthesia is recommended.
      Preconceptional genetic counseling in this autosomal dominant disorder is
      obligatory.

PMID- 8273406
TI  - [Social gerontology--a wide field of responsibility].

PMID- 8273407
TI  - [Contribution to the history of gerontology in Germany in the 2nd half of our
      century].
AB  - In this paper some trends of gerontology during the last 45 years in Germany are
      described. A survey of the development of gerontology in the former GDR is
      followed by an analysis of the "Zeitschrift fur Alternsforschung" from 1980-1990.
      The main result is the predominance of publications on the care system since the
      middle of the 1980s. With regard to the development of gerontology in the western
      part of Germany, an analysis of publications in the "Zeitsschrift fur
      Gerontologie" from 1968-1991 shows changes in the main topics during this period.
      Until the middle of the 1970s there was a predominance of publications in the
      field of: intelligence, learning, memory and perception. The emphasis of
      publications from 1977-1985 was on stress and coping. In the middle of the 1980s
      there was an increasing interest in the analysis of social network and competence
      in the elderly. The paper discusses these trends of gerontological research in
      the eastern and western parts of Germany.

PMID- 8273408
TI  - [Social position and life expectancy. A cohort-specific analysis with data of
      socioeconomic factors].
AB  - The impact of social position on mortality has been explained by a variety of
      underlying causes, among which different living conditions and life-styles of
      social strata, different working conditions, and a selection process are the most
      important. This study relies on an indirect method of evaluating cohort mortality
      and life expectancy. The results confirm considerable impact of social status on
      life expectancy. Furthermore, living conditions as well as working conditions
      seem of relevance, whereas a simple selection process is falsified.

PMID- 8273409
TI  - [Successful Aging and social relations: selection and compensation in social
      contact behavior].
AB  - The model of selective optimization with compensation (Baltes & Baltes 1989;
      1990) offers a theoretical concept of successful aging, that aims at the
      adaptivity of older persons in the aging process. The present study proposes an
      empirical operationalization of the model within the domain of social contact
      behavior, and relates this to self-referent knowledge on daily activities. Older
      persons with multiple chronic diseases and those in generally good health are
      compared according to their self-referent knowledge on daily activities and
      social contact behavior. All participants in the study were socially integrated
      and well functioning. A total of 35 subjects (mean age = 74.4 years) kept a
      prestructured dairy about their social contacts for a period of six days.
      Knowledge on daily activities was assessed in a semi-structured interview. The
      interviews and diaries were content analyzed (inter-rater reliability estimated
      via Cohen's Kappa for the interview: M = 0.84; for the diaries: M = 0.93).
      Results show that the highly social integrated subjects with multiple chronic
      disease performed significantly better in selective and compensatory strategies
      than the subjects in good health. Selection was indicated by (a) less family
      contact and a smaller number of group encounters, (b) more emotional support
      exchange, and (c) more knowledge on maintenance of daily activities. Compensation
      was indicated by (d) more frequent use of the telephone and (e) greater knowledge
      of prosthetic resources. It is concluded that social integration and
      participation can be optimized through selective and compensatory strategies in
      the face of chronic diseases in old age.

PMID- 8273410
TI  - [Retention of relevant and irrelevant information in advanced age].
AB  - In the literature on cognitive aging, differences between the cognitive abilities
      of young and older-adults have long been seen as supporting the view of an age
      dependent cognitive deficit. However, findings are equivocal. In the context of
      more recent findings implying an age-dependent change in the efficiency of
      attentional and inhibition processes, the present study compares two groups of
      young and older adults concerning their ability to solve an everyday-like task.
      In order to effectively solve the task, subjects had to focus on goal-relevant
      information and, at the same time, inhibit irrelevant information. Subjects
      selected the relevant items from a shopping list and subsequently participated in
      a word detection experiment. The results demonstrate older adults taking more
      time overall to solve the task. However, they were differentiating and
      maintaining both relevant and irrelevant information in a way comparable to the
      younger adults. This finding indicates a deficit in older adults concerning the
      speed component of information processing. However, older adults do not seem to
      be impaired in their ability to focus on relevant information.

PMID- 8273411
TI  - ["Ageism": prejudice against age].
AB  - Prejudices against the aged are called ageism. A case demonstrates its obscure
      effects. Ageism is seen as antipathy or hate, too. But a common societal reality
      of ageism is not being able to take different perspectives. Seeing the challenge
      of a concrete clinical situation means varying the ethical perspectives both care
      and fairness. According to that, "multidimensional" assessment characterizes
      geriatrics. Examples for not being able to take varying perspectives are given
      when adults are confronted with suicide, sexuality/tenderness, convictions,
      depression, religiosity, reduced memory capacity, quality of life, incontinence,
      dying etc. of the aged. The paper shows three ways of controlling cognitive and
      affective dimensions of prejudices in general.

PMID- 8273412
TI  - [Older employees in job advertisements in regional and national daily newspapers.
      Results of a pilot study].
AB  - The aim of this pilot study is to investigate the importance of chronological
      age, sex, functional and extra-functional qualifications and job experience in
      the advertisements for positions in daily journals. For that purpose a content
      analysis was carried out with 450 advertisements in national and 150
      advertisements in regional papers. The general result is, that persons in the
      second half of their lives are rarely searched and that there are distinct
      differences in the job requirements in the advertisements of national and
      regional journals.

PMID- 8273413
TI  - [Pensions and adjustment to retirement of employed women].
AB  - The process of women's adjustment to retirement has been widely neglected by
      social scientists. Compared to men, women partly experience greater difficulty in
      adjusting to the retirement process, as the few studies on this subject have
      demonstrated. Results of a qualitative study are reported. The processes of early
      versus normal transition to retirement have been studied in former female
      employees of the German Federal Postal Administration. Despite similar life
      styles and work biographies, different patterns of adjustment emerge due to
      health status and social experiences. These results stress the importance of a
      biographically based approach to the process of adjustment.

PMID- 8273414
TI  - [Importance of social volunteering for elderly and aged women].
AB  - Volunteering is not an unproblematic perspective for elderly women. Practical
      experience as well as scientific research point to the ambiguity of this type of
      work. On one hand, the gender-typed division of labour is continued; access to
      social or political voluntary work reflects the unequality of chances. On the
      other hand, volunteering can open up approaches and perspectives to improve one's
      individual life situation, particularly through social integration, giving a
      meaning to life, and thus gaining better health and psychosocial status.
      Especially in biographical phases, which are marked by losses of life-guiding
      functions and contacts, volunteering may become important. But there are a lot of
      women, who does not have the material and social conditions to manage this work.
      Should volunteering be shaped to fit many elderly women, it needs to be listed on
      the agenda on ageing topic of the ageing and women's policy.

PMID- 8273415
TI  - [Sports programs for the elderly in Germany in 1991].
AB  - The percentage of older people in the population will permanently increase. An
      attendant phenomenon is a rising demand for special exercise programs. In 1991, a
      survey of those programs was done in the unified FRG. The investigation was
      ordered by the Sportministerkonferenz der Lander to substantiate further
      promotion. Organizers and sponsors of exercise programs for older people
      originate from public and private non-profit institutions in the fields of sports
      (administration), social welfare, public health, and educational work. Concerning
      the structure and the extent of special exercise programs there exist large
      regional differences between the eastern vs. western part of the FRG and rural
      vs. urban areas. People of over 50 years of age have to be separated into
      different groups corresponding to their age, physical condition, experience, and
      needs; not all of them find appropriate programs. The Deutsche Turner-Bund,
      private charitable institutions, and a few private health-care organizations
      preferentially serve untrained and/or inexperienced women over 60-65 years of age
      with recreationally oriented exercise programs. The younger, more athletic find
      more competitively oriented programs within the scope of other sports
      federations. Recreational sports programs in age-independent groups are often
      attended by older physically fit people.

PMID- 8273416
TI  - [Decline of competence in aging: an evaluation of the literature on "activities
      of daily living" and need for nursing care].
AB  - The results of a quantitative and qualitative analysis of 36 epidemiological
      studies on competence in activities of daily living and basic care needs in old
      age is presented. On the level of basic activities (ADL), the mean portions of
      elderly people in private households receiving help varied between 1.4% (eating)
      and 7.7% (bathing). With respect to the "instrumental" activities (IADL) cooking
      and shopping, the mean percentages were 14.1% and 17.8%, respectively. The mean
      rate of care needs in the elderly at home amounted to 4.7%. These global scores
      are further differentiated with respect to person variables (age, sex) and study
      characteristics (severity of care needs, inclusion of institutionalized elderly).

PMID- 8273417
TI  - [Family care and caregiver careers. Development of a research paradigm on the
      burden on caregivers by chronically ill, elderly humans].
AB  - Caring for chronically ill older persons in need of nursing care in the family
      depends very much on the internal structure of the family, the capabilities of
      those providing the care and the family's decision to opt for nursing care
      facilities. In this context the family and not (just) the patient becomes the
      crucial point of reference for dealing with illness and nursing care requirements
      on a day-to-day basis. The family thus also becomes the object of analysis from
      the point of view of research strategy. An approach to caring for chronically ill
      older persons oriented towards the biographical context/living environment
      utilizing (retrospective or prospective) "longitudinal" analyses is preferred to
      the traditional rather "linear" cross-section surveys of in situ stress aspects.
      A research paradigm can be developed related to day-to-day concerns that
      systematically analyzes as a process the individual stress situations of persons
      nursing a relative on a day-to-day basis. A future research paradigm would have
      to focus on relatives, not those just reacting to the current situation, but
      those active over a period of time--pursuing "careers" as relatives, as active
      subjects involved in nursing chronically ill older persons.

PMID- 8273418
TI  - [Relinquishing the household and admission to an old age home. What becomes of
      the current life style?].
AB  - The contribution deals with the role of lifestyle in changing residence from a
      private household to an old people's home. This transition not only terminates
      many of the household activities that had structured older women's everyday life,
      but also affects the lifestyle. Anticipation and evaluation of the life situation
      in an old people's home induce people to modify their lifestyles in certain
      dimension in order to compensate for restrictions in other dimensions that are
      expected to ensure from the discontinuation of living at home.

PMID- 8273419
TI  - [Perceived stress and need for psychosocial education/supervision in inpatient
      care of the aged].
AB  - 255 staff persons in the inpatient care of the aged, mainly nursing home staff,
      nurses and assisting personnel, were included in a multicenter questionnaire
      study. As expected, the great majority define their job as nursing, but approx.
      20% identify themselves also with the work of a chaplain or a psychologist. Time
      pressure at work (59%) was reported as the main strain, followed by
      organizational deficits (22%) and compassion with the suffering of some
      inhabitants (20%). Among the positive and motivating aspects of the job teamwork
      and contact with the aged was said to be most important (59% and 57%,
      respectively), followed by autonomy and responsibility in the job. Approximately
      half of the staff expressed high job satisfaction, especially with respect to
      teamwork and the relationship with the aged. Actually staff training and
      supervision is reported to be extremely deficient, more than half confirmed that
      psychosocial staff training and supervision is important and necessary and should
      mainly deal with problems of team interaction and ways of emotional release. Main
      issues desired were aspects of interaction with depressive or aggressive persons
      as well as for caring for the terminal patient. The results clearly stress the
      important role of psychosocial staff training and supervision in this field, in
      order to improve competence as well as to achieve an emotional release and to
      prevent "burnout".

PMID- 8273420
TI  - [Life satisfaction of elderly Turkish migrants].
AB  - Based on the widely spread desire to return to their homeland among elderly
      Turkish migrant workers, the hypothesis was tested that those who plan to return
      to Turkey show more life satisfaction than those who plan to stay in Germany.
      Results of an empirical investigation (questionnaire; (N = 62) did not support
      this assumption. Interviewees who plan to stay in Germany are significantly more
      socially integrated, more satisfied with their situation in old age and look back
      in a significantly more positive way on their lives than those who plan to
      return. These results are discussed as an indication of the need to feel socially
      integrated after spending most of one's lifetime in Germany. The wish to return
      to the homeland does not express a real intention, but rather serves to maintain
      ethnical and cultural identity.

PMID- 8273421
TI  - Reactive Maillard intermediates leading to coloured products-5-hydroxymethyl- and
      5-(1,2-dihydroxyethyl)-3(2H)-furanone.
AB  - In the course of the Maillard reaction, labile sugar degradation products are
      formed that are susceptible to secondary reactions and therefore have a decisive
      influence on the product spectrum. Such reactive intermediates may be transformed
      into stable derivatives with trapping reagents, and thus be protected from
      further reactions. Secondary processes may also be forestalled if the primary
      products are removed from the reaction mixture by high-vacuum distillation. By
      this procedure, 5-hydroxymethyl- and 5-(1,2-dihydroxyethyl)-3(2H)-furanone have
      been identified directly from Maillard reaction mixtures for the first time. The
      activated methylene group of these 3(2H)-furanones can easily enter into
      condensation reactions. The coloured condensation products in turn react with
      primary amines to pyrrolinone derivatives, which may also contribute to the
      colouring observed in non-enzymatic browning.

PMID- 8273422
TI  - Automated determination of total polyphenols in apple juice.
AB  - An automated method of total polyphenols analysis in apple juice using the Folin
      Ciocalteu reagent is presented. Chlorogenic acid was selected as the standard
      since a similar kinetic behaviour, standard-sample, was observed. A
      straightforward method with good reproducibility (CV < 1%), sampling frequency
      (48 h-1) and correlation with the traditional batch method (r = 0.9924) is
      proposed.

PMID- 8273423
TI  - [Crude, digestible and indigestible fruit body proteins in oyster mushroom
      Pleurotus ostreatus].
AB  - Different kinds of protein (crude, digestible, non-digestible) were analysed in
      caps and stipe of Pleurotus ostreatus (oyster mushroom) in four phases of
      development. The phases examined were: a (cap diameter < 5 cm); B (diameter 5-8
      cm); C (diameter, 8-10 cm) and D (diameter > 10 cm). The Pleurotus variety
      analysed (the cap and the stipe) has a relative high crude protein content, the
      main part of which is digestible (average, 92%). During the four stages of fruit
      body ripening, stage B was the best, with the highest crude and digestible
      protein concentrations. In stage D the highest non-digestible protein content was
      measured in the cap and stipe. These data can be used for optimal harvesting of
      fruit bodies of cultivated P. ostreatus.

PMID- 8273424
TI  - [ESR and HPLC studies of the detection of gamma irradiation of eggs].
AB  - Two methods for the identification of irradiated eggs are presented. Electron
      spin resonance (ESR) detects radiation-specific radicals in the calcite matrix of
      eggshells. ESR gives unequivocal results for doses clearly below the
      technologically relevant dose. The stability of the radical in the calcite matrix
      was tested over a period of 6 weeks. Products that contain no or only low amounts
      of fat but a high percentage of protein can be identified by HPLC. Only in the
      chromatograms of irradiated samples is a peak of the amino acid ortho-tyrosine
      present. This HPLC method may be of great interest especially for the
      identification of irradiated pasteurized liquid egg white.

PMID- 8273425
TI  - [Determination of minerals and trace elements in selenium tea from the Enschi
      district, People's Republic of China, and in its infusions using inductively
      coupled plasma-atomic emission spectrometry, graphite furnace atomic absorption
      spectrometry and instrumental neutron activation analysis].
AB  - The Enschi district in Hubei province, Peoples Republic of China is geochemically
      one of the two seleniferous regions, producing both selenium (Se) black tea and
      the Se green tea. Three samples of green tea with different Se contents and one
      non-Se tea were analysed. The following mineral and trace elements were
      determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES):
      K, Ca, Mg, Na, P, S, Al, Mn, Fe, Ba, Sr, Co, Ni, Cu, Zn, Mo, and Cr. Except for
      Mo, Co, and Cr, all other elements in infusions of the samples analysed were also
      measured, since their concentrations are lying over their detection limits. The
      Se content in the tea samples and in the infusions were measured with graphite
      furnace atomic absorption spectrometry (GFAAS). The accuracy of Se determination
      was tested by measuring untreated tea samples with instrumental neutron
      activation analysis (INAA). The Se content in the measured samples was 1 to 8.5
      micrograms/g. In addition to Se, 17 other elements were measured in the tea
      samples and 14 others in the infusions. With this data the extractable part of
      this elements in the infusion were calculated. Up to 10% of the Se was found in a
      first infusion.

PMID- 8273426
TI  - Effect of natural fermentation on carbohydrates, riboflavin and trypsin inhibitor
      activity of lentils.
AB  - Lentils were subjected to natural fermentation for 4 days at 30 degrees C. The pH
      value fell to 3.8 during the process. alpha-Galactosides and sucrose were not
      detected in fermented lentils but a significant increase in the fructose content
      was observed. In fermented lentils the neutral detergent fibre, cellulose and
      hemicellulose contents decreased and the lignin content increased. After
      fermentation the riboflavin content was higher and the trypsin inhibitor activity
      decreased.

PMID- 8273427
TI  - [Planning and implementation of research projects in psychosomatic medicine].
AB  - Based on experiences of the author in planning and realization of scientific
      studies the different phases and steps of research process are discussed.
      Especially in the phases of reflecting and planning of a study, a lot of
      essential preliminary tasks are quite often missed. Failures in these initial
      phases of a scientific study lead to difficulties in collecting and evaluating of
      data. Important steps in the different phases of a project are reported in an
      overview. Finally some typical failures and faults in psychosomatic research made
      by physicians and social scientists are mentioned.

PMID- 8273428
TI  - [The dynamics of special forms of self injury].
AB  - The underlying psychodynamics are described on the basis of investigations
      undertaken with a total of 23 out-patients with self-inflicted lacerations of the
      skin. In many cases autoaggression was not the presenting symptom but was only
      mentioned by the patients in passing. The particular trigger factors and their
      effect is shown in two case descriptions. It appears that differences are
      possible between male and female patients. The character structure of the
      patients is usually narcissistic, the type of defence mechanisms being determined
      by the extent of borderline circumstances always present on first occurrence of
      autoaggression. Later, the original dynamics may become over-shadowed by
      obsessive behavior patterns. Self-inflicted wounds are seen to be part of a
      multiphase process which ultimately allows the patient to cope with narcissistic
      crises experienced as conflict situations. Withdrawal into a state of self
      elected autarchy enables the patient to distance him/herself from the formerly
      idealized object now experienced as evil and disappointing. Pathological
      triangular relationships play a role here with the blood representing an
      important ersatz partner.

PMID- 8273429
TI  - [Symptom-centered psychotherapy in patients with functional voice disorders].
AB  - As a disorder of an ego-function, functional voice disorders display a remarkable
      sensitivity and variability towards psychosocial factors and an often immediate
      connection with the underlying psychic conflict constellation. Being concentrated
      on their symptomatics, patients with functional voice disorders command a good
      capacity of observing their complaints and factors affecting them. Symptom
      centered short-term psychotherapy makes use of the particular character of the
      voice symptom and of the patient's capacity in a focal treatment of the symptom.
      First, a symptom-focus is established on the basis of an analysis of speech
      conflict situations which contains essential psychosocial factors and is
      structured by a psychic conflict constellation. In the further course of
      psychotherapy, the symptom focus is used as a heuristic device in the treatment
      of material of the voice symptomatics. In working through present and past speech
      conflict constellations patients reach an understanding of the psychosocial
      conflict contained in the voice symptomatics and are enabled to develop
      alternatives for changing the maladaptive speech interaction patterns.

PMID- 8273430
TI  - [Subjective illness theories: determinants or epiphenomena of coping with
      illness? A comparison of methods in patients with bronchial cancer].
AB  - The present paper analyzes subjective causal models in lung cancer patients. It
      addresses two questions: 1. What method is apt to assess subjective theories of
      illness? 2. What relationships can be found between subjective theories of
      illness on the one hand and emotional status and coping on the other hand.
      Subjective causes of the disease, assessed by a semi-structured interview and by
      a questionnaire respectively, are compared. Some connections with emotional
      status are tested. Univariate analyses show that certain causal models ("air
      pollution", "psychological cause") co-vary with emotional distress. This
      relationship, however, seems to be a result of a specific way of coping that
      works as a intervening variable, with which both subjective theory and emotional
      distress are confounded. The univariate connection can no longer be maintained
      when this way of coping is included in multivariate analysis. The question is
      discussed, whether subjective causal concepts may be determinants or epiphenomena
      of coping.

PMID- 8273431
TI  - [Epidemiologic findings of the etiology of psychogenic diseases].
AB  - In an epidemiological longitudinal field study, a sample of high risk probands
      suffering from medium psychogenic impairment was investigated with regard to the
      etiological relevancy of factors influencing psychogenic disorders
      (psychoneuroses, character neuroses, psychosomatic and/or psychosomatic
      functional diseases). The study focused the question of the etiological impact of
      personality, life events, and social support. With theoretical reference to the
      psychodynamic concept of personality trained physicians and psychologists
      investigated 240 probands in a half standardized psychodynamic interview which
      included psychometric and social empiric instruments. Expert ratings and self
      ratings were used to assess the current psychogenic impairment. The impact of the
      constructs personality, critical life events, and social support on psychogenic
      impairment was specified in two path models. In both models psychodynamic
      personality variables had the highest impact on the criterium. Psychodynamically
      consistent, the ability to establish mature object relations and the maturity of
      ego functions was inversely related to the degree of psychogenic impairment,
      whereas an immature organisation of defense mechanisms exerted an aggravating
      influence on the severity of impairment. The present path analyses altogether
      point to a possible central etiological impact of personality and/or
      psychodynamic variables on the severity of psychogenic impairment.

PMID- 8273432
TI  - The fetal ductus arteriosus, a review.
AB  - The developmental biology of the human ductus arteriosus is reviewed from its
      origins in the 6th branchial arch to its ultimate closure and obliteration in the
      neonatal period. Different concepts of ductal maturation are discussed and the
      role of prostaglandins in this process are highlighted. Recent advances in
      Doppler ultrasound have made it possible to observe and measure fetal ductus
      arteriosus blood flow as early as 11 weeks of gestation. During indomethacin
      tocolysis ductal constriction can be monitored with Doppler ultrasound in order
      to stop indomethacin administration when necessary, thus making indomethacin
      tocolysis safer.

PMID- 8273433
TI  - [Diagnostic problems in HELLP syndrome--presented with reference to 20 case
      reports].
AB  - 15 so-called "definite" cases and five so-called "questionable" cases of HELLP
      Syndrome are reported and discussed. The cases demonstrate the chameleon-like
      behaviour of symptoms and how difficult it can be to avoid it's full
      manifestation even if careful attention is paid to liver enzymes or platelets.
      Elevated liver enzymes and low platelets are also found in normal pregnancies
      making differential diagnosis more difficult as the retrospective analysis of
      laboratory findings of more than 2000 normal pregnancies shows. Even though,
      careful attention should be paid to detect any early laboratory finding or
      clinical sign of HELLP-Syndrome in order to prevent dramatic outcomes. Any
      symptoms of gestosis should be reason to determine not only liver enzymes and
      platelets, but also haptoglobin as the latter seems to detect early hemolysis in
      a beginning HELLP-Syndrome.

PMID- 8273434
TI  - Non-invasive diagnosis of bladder instability using the Bladder Instability
      Discriminant Index (BIDI).
AB  - The purpose of this study was to validate prospectively the BIDI index in the non
      invasive diagnosis of bladder instability, as a procedure for clinical evaluation
      in primary health care of women. 217 patients were studied; 82 with stress
      incontinence, 39 with urge incontinence and 96 with both symptoms. All patients
      were studied by specialist physicians, who conducted a clinical evaluation,
      questionnaire, gynecological and urological examination, stress test, urodynamic
      assessment and a 7 day frequency/volume study, recording each intake and
      micturition; data that were used to calculate the BIDI index. The results
      obtained through the application of the BIDI were compared with the corresponding
      urodynamic diagnoses, achieving 88% sensitivity and 83% specificity. The use of
      the BIDI index is suggested as a non-invasive clinical diagnostic method, of low
      cost and simple performance. It is recommended for treatment control and for
      taking diagnostic and therapeutic decisions in medical centres lacking proper
      urodynamic equipment.

PMID- 8273435
TI  - Late complications of gestational diabetes--maternal effects.
AB  - In the material of the Diabetic Outpatient Department and Consulting Unit of the
      Department of Obstetrics and Gynecology, Debrecen, Medical University, the author
      studied the effects of gestational diabetes on pregnant women and their fetuses
      in 75 cases with repeated gestations. The author observed that 13 out of the 75
      prior gestational diabetic women had manifest diabetes during the second
      pregnancy. Insulin demand increased gradually during the gestational period and
      where therapy was needed the treatment had to be started at the 20th week of
      gestation, instead 27th. In the next pregnancy a higher dose of insulin is
      required (18 and 23 U/day). Finally the author emphasized on the regular follow
      up of such high-risk population.

PMID- 8273436
TI  - [Increased uterine activity through histamine].
AB  - The influence of histamine, a biogenic amine known for many years, on the
      contractility of uterine specimens, was investigated. A highly significant (p >
      0,0001) increase of uterine activity after the application of histamine 10(-6) M
      was observed, caused by a similar increase of frequency, duration and amplitude
      of the contractions.

PMID- 8273437
TI  - [Obstetrical damage to the symphysis].
AB  - Extension or rupture of the symphysis pubis result to obstetrical lesions of the
      symphysis. Causes, diagnostic and treatment are demonstrated on our own 27 cases.

PMID- 8273438
TI  - [Granular cell tumor of the breast].
AB  - Report about a 46 year old women with granular cell tumor of the breast. Clinical
      features, mammography and sonography has appearances highly suspicious for breast
      cancer. Tumorectomy and axillary lymphonodectomy were performed. Estrogen and
      progesterone receptor both were histochemically and biochemically negative.
      Estradiol and prolactin levels in serum were normal. Cathepsin D in cytosol was
      slightly elevated, DNA-flow-cytometry revealed no signs of malignancy. Evident
      was the high content of protein S100 in cytosol of tumor cells.

PMID- 8273439
TI  - [Early cancer detection--advanced vulvar cancer: a contradiction?].
AB  - Gynecologic cancer screening examination is not accepted on a large scale. The
      reasons for this have been discussed by means of an example of a progressive
      vulvar cancer. Women should be urgently referred to self examination.

PMID- 8273440
TI  - [Cardiotocography practice case no. 25. Fetal movements produce reactive changes
      in heart rate].

PMID- 8273441
TI  - Bone remodelling in the presence of chondrosarcoma: histomorphometry.
AB  - Accurate knowledge of tissue changes near bone tumors can contribute to a better
      understanding of tumor behavior. We have used tumor ultrastructure and
      quantitative bone histomorphometry to evaluate local bone/tumor features
      associated with a low grade chondrosarcoma in a 39-year-old male. Three
      noninvolved sites and two sites near the tumor in the proximal femur were studied
      with bone morphometry. Bone near the tumor showed increased percent osteoid
      surface, percent osteoid volume and fraction of osteoid surface lined by
      osteoblasts compared to distant noninvolved sites. Both the number of osteoblasts
      and mean individual osteoblast size were significantly increased compared to
      noninvolved sites. Osteoclast number and percent osteoclast surface were also
      increased near the tumor. Ultrastructural studies of tumor tissue revealed two
      types of tissue: synthetic mesenchymal cells and cartilage tissue. Results
      indicate increased bone formation and resorption near the tumor. These local bone
      changes may possibly reflect responses to local tumor factors and depend on the
      extent of the tumor.

PMID- 8273442
TI  - Effects of clomiphene citrate on vaginal epithelium of ovariectomised rats.
AB  - Scanning electron microscopy and light microscopy have been used to study changes
      to the vaginal epithelium induced by exogenous hormones and clomiphene citrate
      (CC) administered to ovariectomised rats. Oestrogen (E2) administration resulted
      in epithelial cell proliferation and keratinisation. The administration of the
      E2/anti-E2 CC also resulted in the stimulation of cell proliferation, but not to
      the extent produced by E2. Lack of keratinisation, a decreased number of
      epithelial layers and decreased epithelial height were viewed as non-oestrogenic,
      or retarded oestrogenic, effects of CC. Modifications to the surface of vaginal
      luminal cells were also apparent following CC treatment. Cell apices were raised
      and separated by prominent borders; the surface covering consisted of short bulb
      tipped microvilli that clumped together to form rosettes. Individual, elongated
      microvilli were also evident. The results of this study indicate that CC has
      retarded oestrogenic actions, as well as a unique ability to alter cell and
      surface morphology to produce characteristics dissimilar to those seen after
      treatment with E2 and progesterone.

PMID- 8273443
TI  - Effect of maternal phenobarbital consumption on muscle development in mice.
AB  - The effect of prenatal exposure to phenobarbital on muscle development was
      determined in 4 muscles (biceps brachii, triceps brachii, soleus and cranial
      tibial) of 34 mice (16 males, 18 females) at 12 weeks of age. The control group
      received unadulterated food ad libitum throughout the period of study. The
      phenobarbital-exposed group received 3 g of phenobarbital per kilogram of food
      from gestation day 7 to 18 as the only source of food. Outside this period they
      received unadulterated food and water ad libitum. Each mouse was killed at 12
      weeks of age. The muscle mass of control mice was significantly larger than that
      of the phenobarbital-exposed group in both sexes. The smaller muscle mass of the
      phenobarbital-exposed group as observed from the analysis of the soleus muscle
      was due to a smaller number of muscle fibres being present than in the control
      group, since the muscle fibre sizes were similar in both groups. This indicated
      that prenatal administration of phenobarbital inhibits normal hyperplasia of
      muscle fibres.

PMID- 8273444
TI  - The right atrioventricular valvular apparatus in the chick heart.
AB  - The purpose of this study was to describe the detailed anatomy and histology of
      the right atrioventricular valve apparatus in the chicken. Newborn and adult
      chicken hearts were studied by anatomic description, light and scanning electron
      microscopy, and histologic (Masson's trichrome stain) and histochemical (Sirius
      Red stain) techniques. Our findings indicate the presence of an incomplete
      fibrous annulus, a great mural leaflet, and multiple microleaflets in the right
      atrioventricular apparatus of the chicken heart. The great mural leaflet,
      essentially muscular in structure, extended from the anterior and posterior
      juxtaseptal commissures and was subdivided into an anterior and a posterolateral
      region by the attachment of the anterolateral papillary muscle. The
      posterolateral region presented an intermediate cleft, subdividing this region
      into an anterior and a posterior portion. Multiple microleaflets, which adhered
      to the upper right side of the ventricular septum adjacent to the right
      atrioventricular orifice, inserted directly into the ventricular septum via short
      chordae tendineae, without papillary muscles. The microleaflets were composed of
      smooth subendocardial connective tissue, with varying amounts of type I, II and
      III collagen. In addition, we observed a central fibrous body, leading to fibrous
      continuity between the mitral and aortic valves and the mitral and right
      atrioventricular valves. An atrioventricular septum was also present.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8273445
TI  - Serotonin-immunoreactive terminals in the mesencephalic trigeminal nucleus of the
      rat: an electron microscopic immunocytochemical study.
AB  - The morphological characteristics and distribution of serotonin-immunoreactive
      terminals within the rat mesencephalic trigeminal nucleus (Me5) were studied
      using immunocytochemical electron microscopy. Fibers, immunostained by specific
      antibodies raised against serotonin, were distributed throughout the entire
      rostrocaudal portion of the Me5. Examination of 355 serotonergic terminals in the
      caudal part of the Me5 revealed that 93% formed synaptic contacts with dendritic
      shafts: 68% on small (< 1.5 micron diameter) and 25% on large (> 1.5 micron
      diameter) dendrites. The remaining 7% formed axosomatic synapses, about a third
      of which are in contact with small spinous processes (somatic spines). Serotonin
      was also present in vesicle-filled boutons lacking synaptic-membrane
      specializations. Our data indicate that of all the dendritic synaptic and
      nonsynaptic inputs observed in the Me5 nucleus, the serotonergic component
      amounted to between 15 and 27%. More than half (58%) of the somatic synaptic
      input on the Me5 cells appears to be serotonergic. This suggests that, of all the
      somatic synaptic input on the proprioceptive primary sensory neurons of the Me5,
      the serotonergic afferent input probably has the most significance for the
      functioning of Me5 neurons.

PMID- 8273446
TI  - Studies of the motoneurons following the injection of horseradish peroxidase into
      the peripheral branches of the facial nerve in rats.
AB  - With the method of retrograde transport of horseradish peroxidase, the present
      study demonstrated a topographical representation of the peripheral branches of
      the facial nerve within the rat facial nucleus. The labelled neurons relating to
      the different peripheral branches were characterized morphometrically with the
      aid of an image analyser system. While the results were in general agreement with
      the work of other investigators, a striking difference was observed in this study
      with respect to the spatial distribution of the labelled neurons of the cervical
      branch. In the latter, the cells of origin were derived from the dorsal parts of
      the lateral and intermediate division of the facial nucleus. The present study
      further demonstrated that the motoneurons giving rise to the respective
      peripheral branches of the facial nerve varied considerably in cell size. Thus,
      the neurons of the posterior auricular and the mental branches were significantly
      larger than those of the nasolabial and zygomatico-orbital branches. Another
      significant finding in this study was that the neurons supplying the mental
      branch were predominantly spindle-shaped. It is concluded that the heterogeneity
      in size and shape of the motoneurons in the facial nucleus is related to the
      topographical representation of the peripheral branches of the facial nerve.

PMID- 8273447
TI  - Microvascularization of the common tree shrew (Tupaia glis) superior cervical
      ganglion studied by vascular corrosion cast with scanning electron microscopy.
AB  - Microvascularization of the superior cervical ganglion (SCG) of the common tree
      shrew (Tupaia glis) was investigated by the vascular-corrosion-cast technique in
      conjunction with scanning electron microscopy. It was found that the SCG of the
      tree shrew is a highly vascularized organ. It receives arterial blood from
      branches of the external and common carotid arteries which enter the rostral and
      caudal portions of the ganglion. These arteries give rise to a subcapsular
      capillary plexus before branching off to form a group of densely packed
      intraganglionic capillaries. Moreover, the intraganglionic capillaries tend to
      follow a tortuous course that is essentially parallel to the longitudinal axis of
      the ganglion, and they form anastomoses with each other. In addition, the
      intraganglionic capillaries are also connected to a subcapsular capillary plexus.
      The capillaries of the SCG converge into venules and collecting veins which
      subsequently drain rostrally and caudally into the systemic veins. However,
      neither a pattern of blood vessels resembling glomeruli nor a portal-like
      intraganglionic microcirculation was observed.

PMID- 8273448
TI  - Anatomical study of the branches emerging along the intracavernous course of the
      internal carotid artery in humans.
AB  - The introduction in the sixties of magnification tools in surgery has created the
      need for a precise anatomical knowledge of morphological structures that was
      previously unnecessary from a clinical perspective. In the present paper, we have
      centred our attention on the intracavernous portion of the internal carotid
      artery (arteria carotis interna) in humans for applicative purposes. With the aid
      of a surgical microscope and the corresponding microdissecting material we have
      analysed the branches emerging from this arterial segment. Our results are
      compared with previous data appearing in the literature, the latter sometimes
      confusing because of the different terminologies used to refer to these vessels.
      The elements under study varied greatly, but some basic variational parameters
      were deduced.

PMID- 8273449
TI  - An accessory flexor digitorum longus muscle.
AB  - An accessory flexor digitorum longus muscle (M. flexor digitorum longus
      accessorius) in a 60-year-old male cadaver was encountered during routine
      dissections in our laboratory. The muscle originated from the deep transverse
      fascia of the leg, covering flexor digitorum longus, flexor hallucis longus, and
      tibialis posterior muscles, and additionally from some fibres of these muscles.
      After the tendon of the muscle passed behind the medial malleolus, it inserted
      into the tendon of the flexor digitorum longus muscle where the latter separated
      into four digital tendons.

PMID- 8273450
TI  - Apocrine secretion in the infraorbital gland of the Japanese serow, Capricornis
      crispus: a scanning electron-microscopic study.
AB  - The infraorbital gland of the Japanese serow was examined under the scanning
      electron microscope to clarify the nature of apocrine secretion. The size and
      number of apocrine blebs on secretory cells varied markedly from cell to cell; as
      the size of blebs increased, their numbers decreased. After pinching off of
      blebs, crown-shaped structures were retained on the remaining apical surface of
      secretory cells. Detached free blebs in the lumen were spherical in shape with
      smooth surfaces. Secretory cells having blebs of similar size formed small
      clusters in tubules, and these clusters consisted of cells without blebs, cells
      with small blebs, cells with medium-sized blebs and cells with large blebs. The
      present evidence obtained by scanning electron microscopy is very much in harmony
      with results obtained at the light-microscopic level in terms of the sizes and
      numbers of blebs during apocrine secretion. Moreover, our evidence suggests the
      capacity for production of variously sized blebs in secretory cells and the
      presence of segmentary differences, in terms of apocrine activity, in tubules.

PMID- 8273451
TI  - Blood flow and oxygen uptake in the human brain during various states of sleep
      and wakefulness.

PMID- 8273452
TI  - Hydrostatic pressure in the inner ear fluid compartments and its effects on inner
      ear function.
AB  - The present study summarizes the experimental findings obtained on the pressure
      in the inner ear fluids and on the effects of pressure changes on cochlear
      function in the guinea pig. Two types of pressures have to be distinguished in
      the inner ear fluid compartments: (i) hydrostatic fluid pressure and (ii)
      superimposed hydrodynamic high frequency (> 100 Hz) sound pressure oscillations.
      Hydrostatic pressure in the inner ear fluids in guinea pigs is in the order of
      200 Pa (2 cm H2O) and shows slow (< 5 Hz) respiratory and pulsatory oscillations
      as well as considerable physiological variations in the range of -100 to +700 Pa.
      In normal ears, hydrostatic pressure in the perilymph equals pressure in the
      endolymph, and pressure changes applied to one compartment are immediately
      transmitted to the other one. A high compliance of Reissner's membrane seems to
      be the cause of this endolymphatic-perilymphatic pressure equalization. In
      experimental endolymphatic hydrops, a unique animal model for Meniere's disease,
      endolymphatic pressure is higher (100 Pa and above) than perilymphatic pressure.
      These pressure gradients occur only in late stages of hydrops, probably when
      Reissner's membrane has lost its high compliance after long standing distension.
      Positive endolymphatic-perilymphatic pressure gradients are secondary to and not
      the primary cause of hydrops formation. Changes of hydrostatic pressure do not
      affect auditory function as long as they stay in the physiological range. This
      includes the sudden loss of positive inner ear pressure that occurs in perilymph
      fistulas. The rationale for surgical repair of perilymph fistulas in patients in
      order to restore the hearing function thus becomes questionable. Other aspects of
      surgical repair, however, as e.g. prevention of labyrinthitis due to permanently
      open fistula, could not be investigated in this model, because in guinea pigs
      even large fistulas heal spontaneously within a few days. In experimental
      endolymphatic hydrops, deterioration of auditory thresholds was partially
      correlated to the presence of positive endolymphatic-perilymphatic pressure
      gradients. A change in pressure, however, occurred later than the first
      deterioration in auditory function. Therefore positive endo-perilymphatic
      pressure gradients may contribute to, but are not the only cause of hearing
      impairment.

PMID- 8273453
TI  - Effects of an aldose reductase inhibitor, SNK-860, on the histopathological
      changes of retinal tissues in a streptozotocin-induced diabetic rat model.
AB  - In order to clarify the mechanism of retinal tissue damage in diabetes mellitus,
      the effects of the inhibition of aldose reductase on the pathologic changes in
      the retina of streptozotocin-induced diabetic (STZ-diabetic) rats were examined
      histologically and histochemically. The STZ-diabetic animals were maintained with
      and without peroral administration of an aldose reductase inhibitor, SNK-860, and
      their retinas were examined microscopically after 12 months. Several abnormal
      changes observed; folding and edema in the retina, loss of pericytes in the
      retinal capillary walls, and thickening of basement membranes in the retinal
      capillaries, were significantly inhibited by SNK-860. Some of these changes were
      similar to those that had been previously noted in diabetic and galactosemic
      rats. These data suggest that the enhanced polyol metabolism may be involved in
      the diabetic changes of the retina.

PMID- 8273454
TI  - Autoimmune responses as assessed by hypergammaglobulinemia and the presence of
      autoantibodies in patients with chronic hepatitis C.
AB  - We investigated autoimmunity, as assessed by hypergammaglobulinemia and the
      presence of autoantibodies including anti-nuclear antibodies (ANA) and anti-liver
      membrane antibodies (LMA), in 149 patients with chronic hepatitis C, 55 patients
      with chronic hepatitis B and 11 patients with autoimmune hepatitis. There was no
      significant difference in the incidence of these autoantibodies between chronic
      hepatitis C and chronic hepatitis B. Nine patients with chronic hepatitis C
      satisfied the serological criteria of autoimmune hepatitis (ANA positive and
      gammaglobulin or serum IgG greater than 2500 mg/dl), but none of the patients
      with chronic hepatitis B met the criteria. This suggests that autoimmunity is
      greater in chronic hepatitis C than in chronic hepatitis B. Of the 9 patients
      with chronic hepatitis C, all 4 patients tested for human leukocyte antigen (HLA)
      phenotype had HLA-DR4, which is known to be associated with autoimmune hepatitis
      in Japanese patients. We believe that hepatitis C virus (HCV) infection enhances
      the initiation and perpetuation of autoimmunity in susceptible individuals.

PMID- 8273455
TI  - Detection of negative strand RNA of hepatitis C virus in infected liver and
      serum.
AB  - The negative strand RNA of hepatitis C virus, supposed to be a replicative
      intermediate of the virus appears to indicate viral replication. In this study,
      we detected the negative strand RNA by using reverse transcription-polymerase
      chain reaction with RNase A digestion to degrade the remaining positive strand
      genomic sequence of the virus after complementary DNA (cDNA) synthesis. In vitro
      transcribed positive-stranded mutant RNA was not detected by this method. Sample
      sera and liver tissues of 16 patients with chronic hepatitis C virus infection
      (liver fibrosis, 1; chronic hepatitis, 13; liver cirrhosis, 2) were analysed for
      negative strand RNA of hepatitis C virus. The negative strand RNA sequence was
      detected in 15 (93%) of 16 liver tissues and in 11 (78%) of 14 sera. The study
      demonstrated that negative strand RNA of hepatitis C virus in serum and liver
      tissue could be specifically detected.

PMID- 8273456
TI  - Evaluation of the viability of the canine cadaver lung for transplantation.
AB  - We evaluated the viability of the cadaver lung and the effect of lung inflation
      with 100% oxygen using a canine allotransplantation model. Donor animals were
      killed by potassium chloride (KCl) injection and were kept at room temperature
      until lung extraction. The animals were divided into the following 3 groups:
      group 1 (n = 6) in which the donor lungs were retrieved 2h after sacrifice, group
      2 (n = 6) in which the donor lungs were retrieved 3h after sacrifice, and group 3
      (n = 6) in which the donor lungs were retrieved 3h after sacrifice as in group 2
      except that they were kept inflated for 3h with 100% oxygen using a double lumen
      endotracheal tube. Heparin was not given and lungs were not flushed with
      preservation solution. After left lung transplantation, the transplanted lung
      function including gas exchange and pulmonary hemodynamics was assessed for 6h by
      ligating the right pulmonary artery of the recipient animals. All 6 animals in
      groups 1 and 3 survived for 6 h with excellent lung function. Only 2 of 6 animals
      in group 2 survived for 6h with poor lung function. These results led us to
      conclude the following: a) the cadaver lung kept at room temperature for 2h might
      be available for lung transplantation, and b) when the cadaver lung is inflated
      with 100% oxygen, the length of safe ischemic time could be prolonged up to 3h.

PMID- 8273457
TI  - Survival simulation of hepatocellular carcinoma derived from follow-up studies of
      450 patients.
AB  - A simulation model to predict the survival probability of individual patients
      with hepatocellular carcinoma (HCC) after therapy was derived from the results of
      various therapies and follow-up studies of 450 HCC patients. Twenty-two
      prognostically important variables were analyzed by Cox's proportional hazards
      model. The 9 significant variables that were extracted were used to build the
      simulation. In this model, S(t), the expected estimated survival rate for
      individual patient at time t (month), is calculated by the following equation:
      S(t) = (exp (-0.03655t) (exp [0.9479 ([portal vein invasion]-0.222) + 0.3846
      ([tumor number]-2.00) + 0.2578 ([tumor size]-3.231) + 0.0742 ([loge AFP]-5.647) +
      0.8184 ([metastasis]-0.036) + 0.2810 ([Child's class]-1.689)-0.7088
      ([transcatheter arterial embolization]-0.578)-0.9746 ([percutaneous ethanol
      injection]-0.153)-0.5377 ([hepatectomy]-0.109)]) The validity of the model was
      assessed using a split-sample technique. This paper does not discuss the
      superiority or inferiority of the therapies, because some selection bias for
      prognostic factors among the therapies can not be completely excluded. But this
      model is proposed as a practical model to predict the survival of patients with
      HCC.

PMID- 8273458
TI  - Successful pregnancy in renal transplant recipients.
AB  - Three cases of successful pregnancies in renal transplant recipients who had
      undergone transplantation in the Okayama University Medical School Hospital are
      reported. Two of the women had received an organ from a living relative and one
      woman received a cadaveric organ graft. These patients, aged 28-37 at the time of
      the delivery, had received their transplants 2-5 years prior to their conception.
      The periods of gestation ranged between 35 and 40 weeks. The weight of the babies
      at birth ranged from 2,380g to 2,500g and the apgar score at 1 min was 8 or 9.
      None of the infants showed any congenital abnormalities. Lower-segment cesarean
      section was performed in all of three cases. Serum creatinine levels, an
      indicator of renal graft function, did not deteriorate during the pregnancy or
      after delivery. Although further work is needed to solve problems regarding
      pregnancy in renal transplant recipients, these results encouraged us to meet
      their hope for a baby.

PMID- 8273459
TI  - Common bile duct injury during laparoscopic cholecystectomy.
AB  - Bile duct injury can occur more frequently during laparoscopic cholecystectomy
      than in open cholecystectomy. Three cases of common bile or hepatic duct injuries
      occurred in a series of eighty laparoscopic cholecystectomies; In case 1, the
      common bile duct was misidentified as the cystic duct. In case 2, bile
      peritonitis occurred on the fourth postoperative day caused by necrosis of the
      common hepatic duct involving the cautery surrounding it. In case 3, a bile leak
      occurred due to an incision at the confluence of the cystic and common duct.
      Dissection of the cystic duct at the infundibulum of the gallbladder, blunt
      dissection of the Calot's triangle, the handling of clips with special attention
      for safety were thought to be necessary in order to lower the risk of bile duct
      injury. Preoperative endoscopic retrograde cholangiography (ERCP) is recommended
      to avoid bile duct injury.

PMID- 8273460
TI  - Cochlear implants: new perspectives. Symposium, Toulouse, June 2-3, 1992.
      Proceedings.

PMID- 8273461
TI  - Cochlear implants: past, present and future.

PMID- 8273462
TI  - Preoperative electrical nerve stimulation as one of the criteria for selection.

PMID- 8273463
TI  - Ear canal electrodes versus promontory electrodes in preoperative electrical
      stimulation for cochlear implant selection.

PMID- 8273464
TI  - Is the round-window electrical test possible in children?

PMID- 8273465
TI  - Brain stem evoked responses by intracochlear electric stimulation.

PMID- 8273467
TI  - Electrical brain stem responses in cochlear implant patients.

PMID- 8273466
TI  - Auditory brain stem response evoked by electrical stimulation with a cochlear
      implant.

PMID- 8273468
TI  - Application of intraoperative recordings of electrically evoked ABRs in a
      paediatric cochlear implant programme. Nottingham Paediatric Cochlear Implant
      Group.

PMID- 8273469
TI  - Predictive factors in cochlear implant surgery.

PMID- 8273470
TI  - Prognostic factors in 187 adults provided with the Nucleus cochlear mini-system
      22.

PMID- 8273471
TI  - Multivariate predictors of success with cochlear implants.

PMID- 8273472
TI  - Tinnitus suppression in cochlear implant users.

PMID- 8273473
TI  - Three-dimensional reconstruction of the cochlea and temporal bone.

PMID- 8273474
TI  - Sound localization with the Ineraid cochlear implant.

PMID- 8273475
TI  - Cochlear implantation in the deaf blind.

PMID- 8273476
TI  - Ethical and medicolegal aspects of multichannel cochlear implantation in
      children.

PMID- 8273477
TI  - Multichannel cochlear implantation in prelingually and postlingually deaf
      children.

PMID- 8273478
TI  - Interactive software for setting cochlear implants in children.

PMID- 8273479
TI  - Audiovisual test programs in native languages. Test material in Norwegian on a
      video disc controlled by laser bar code.

PMID- 8273480
TI  - An audiovisual feature test for young deaf children in English, French, Spanish
      and German.

PMID- 8273481
TI  - Long-term follow-up of Nucleus cochlear implant patients.

PMID- 8273482
TI  - Cochlear implants in adolescents.

PMID- 8273483
TI  - Curricula objectives for educators of children with cochlear implants.

PMID- 8273484
TI  - Results in patients with congenital profound hearing loss with intracochlear
      multichannel implants.

PMID- 8273485
TI  - Place of 3DFT-MR imaging study on cochlear implant candidates.

PMID- 8273486
TI  - Preliminary speech perception results for children with the 22-electrode
      Melbourne/cochlear hearing prosthesis.

PMID- 8273487
TI  - Total obstructed cochlea and cochlear implant.

PMID- 8273488
TI  - Postoperative speech perception results for 92 European children using the
      Nucleus Mini System 22 cochlear implant.

PMID- 8273489
TI  - Auditory brain stem implant: electrical stimulation of the human cochlear
      nucleus.

PMID- 8273490
TI  - The 8-channel cochlear implant CAP: first results.

PMID- 8273491
TI  - A new behind the ear wearable speech processor for the Vienna cochlear
      prosthesis.

PMID- 8273492
TI  - The Laura cochlear implant programmed with the continuous interleaved and phase
      locked continuous interleaved strategies.

PMID- 8273493
TI  - Experience with four different cochlear implant systems.

PMID- 8273494
TI  - Cochlear implants in Europe: costs and benefits.

PMID- 8273495
TI  - Auditory cortex activities in severely hearing-impaired and cochlear implant
      patients. Positron emission tomographic study.

PMID- 8273496
TI  - The contribution of brain mapping in the wearer of a cochlear implant.
      Preliminary report.

PMID- 8273497
TI  - Responses from single units in the dorsal cochlear nucleus to electrical
      stimulation of the cochlea.

PMID- 8273498
TI  - Steady state evoked potentials: a new tool for the accurate assessment of hearing
      in cochlear implant candidates.

PMID- 8273499
TI  - Multichannel implants in postmeningitic ossified cochleas.

PMID- 8273500
TI  - Surgical difficulties with cochlear implants.

PMID- 8273501
TI  - Intracochlear electrode placement facilitated by Healon.

PMID- 8273502
TI  - Problems in cochlear implant surgery.

PMID- 8273503
TI  - Surgical complications of multichannel cochlear implants in North America.
AB  - By paying careful attention to the details of surgical technique, many of the
      complications which have occurred to date may be avoided. Some, such as late
      electrode and receiver/stimulator migration, device failures, and late flap
      necrosis due to excessive magnetic forces cannot be avoided by the surgeon, but
      may be prevented by further advances in implant designs. Although the incidence
      of life-threatening complications is minimal, and that of major complications is
      acceptable, every effort should be made by the surgeon, audiologist and
      manufacturer to further diminish these problems.

PMID- 8273504
TI  - Implant generated surface potentials and (partial) device failures of the Nucleus
      cochlear implant.

PMID- 8273505
TI  - Comparative reliability of cochlear implants.

PMID- 8273506
TI  - Comparison of current speech coding strategies.

PMID- 8273507
TI  - A study of monopolar and bipolar stimulation modes with a modified Nucleus Mini
      22 cochlear implant.

PMID- 8273508
TI  - A hybrid coding strategy for a multichannel cochlear implant.

PMID- 8273509
TI  - Significance of the promontory test: histological and electrical results.

PMID- 8273510
TI  - Transhepatic solute transport and bile formation.

PMID- 8273511
TI  - Equine fasting hyperbilirubinemia.
AB  - It appears that different mechanisms responsible for fasting hyperbilirubinemia
      may be operative in different mammalian species (and subspecies). An increase in
      bilirubin production does not seem to occur in the horse, but a decrease in the
      hepatic uptake of bilirubin has been supported by a number of studies. Even
      though the delay in plasma elimination could also result from a decrease in
      hepatic blood flow, this possibility does not seem to play a major role since the
      hepatic uptake of compounds with low intrinsic hepatic clearance (e.g., ICG and
      bilirubin) appear to be affected more during fasting than those with higher
      clearances (e.g., BSP, bile acid, antipyrine, acetaminophen, and lidocaine)
      (Table I). Other possibilities such as a decrease in the affinity of
      hepatocellular membrane carriers involved in the uptake of these compounds or
      altered content of intracellular proteins involved in cellular transport or
      storage of bilirubin have not been investigated in horses. Competition with free
      fatty acids for these carrier-mediated events seems likely, particularly because
      horses and ponies experience high degrees of hyperlipidemia during fasting.
      However, studies that have explored the competition hypothesis, while not
      entirely negative, do not fully support it as being the sole mechanism
      responsible for this phenomenon. Hepatocellular UDPGT activities have not been
      adequately investigated in horses, but it is apparent that intraduodenal infusion
      of glucose is effective in reducing fasting hyperbilirubinemia and also in
      increasing biliary bilirubin excretion. It therefore seems possible that UDP
      glucose and UDPGA levels in the livers of horses could be reduced during fasting,
      thus resulting in substrate depletion for the conjugating enzymes. As pointed out
      by Freedland et al. (1991), it is also possible that the horse, like the Bolivian
      squirrel monkey, might also have a relatively high apparent Km and low Vmax for
      UDPGT, thus resulting in high steady-state levels of plasma bilirubin,
      particularly during fasting. Although little is known about the cause of equine
      fasting hyperbilirubinemia and the subtle factors that may be modulating slight
      changes in the production, hepatocellular uptake, binding, conjugation, and/or
      biliary excretion of this pigment, it is known that it can be rapidly reversed by
      refeeding native hay. Perhaps one direction for future research could point
      toward more fully exploring what aspects of feeding are responsible for reversing
      this intriguing physiological phenomenon.

PMID- 8273512
TI  - Fasting hyperbilirubinemia in Bolivian squirrel monkeys with a Gilbert's-like
      syndrome.
AB  - Fasting unconjugated hyperbilirubinemia in Bolivian squirrel monkeys is most
      likely due to two mechanisms. First, a twofold increase in bilirubin
      production/turnover occurs during fasting. Increased bilirubin production is
      subsequently accompanied by increased amounts of unconjugated bilirubin in the
      hepatic cytosol, which requires conjugation for excretion. The presence of a
      twofold greater concentration of bilirubin in the livers of fed BoSM with the
      Gilbert's-like syndrome than in fed control Brazilian squirrel monkeys (BrSM)
      clearly establishes the presence of an innate subspecies difference, even without
      the effects of fasting. A second mechanism, which is responsible in part for FH
      in BoSM, is the presence of a hepatic enzyme, UDP-glucuronyl transferase, which
      has a higher apparent UDPGAKm and a lower Vm; this results in higher steady-state
      plasma and hepatic bilirubin levels during a fast when hepatic UDP-glucuronic
      acid levels are low. The BoSM provides the investigator with an excellent animal
      model for human Gilbert's syndrome type I in which to study rate-limiting
      mechanisms in the transport of bilirubin from plasma to bile.

PMID- 8273513
TI  - Gunn rat: a model for inherited deficiency of bilirubin glucuronidation.
AB  - Experiments in Gunn rats have provided important insights into physiological,
      biochemical, and molecular mechanisms of bilirubin conjugation and disposition.
      The Gunn rat is a natural model for bilirubin encephalopathy, and much of our
      knowledge of bilirubin toxicity and its treatment has come from studies performed
      in Gunn rats. The genetic lesion in Gunn rats closely parallel those in Crigler
      Najjar syndrome, Type I. Presently, the Gunn rat model is being used to develop
      methods for gene therapy for inherited bilirubin-UGT deficiency. Thus, Gunn rats
      continue to be a valuable model for the investigation of inherited UGT deficiency
      and severe nonhemolytic unconjugated hyperbilirubinemia.

PMID- 8273514
TI  - Hereditary conjugated hyperbilirubinemia in Wistar rats: a model for the study of
      ATP-dependent hepatocanalicular organic anion transport.

PMID- 8273515
TI  - Biliary atresia in lampreys.
AB  - The preceding pages have described an organism that is far removed from mammals
      on the taxonomic scale of vertebrates but one that has proven to have a unique
      and most useful system for studies of liver function and, in particular, bile
      product transport and excretion. It is also an organism in which iron loading can
      be studied in the liver and other organs and tissues. Many of the events that
      occur in this animal during its life cycle with regard to bile pigment metabolism
      as normal programmed phenomena are unparalleled among the vertebrates. In the
      larval (ammocoete) period of lampreys, there is an intrahepatic gallbladder and a
      biliary tree that is well equipped for the storage, transport, and elimination of
      bile products into the intestine for ultimate excretion with the feces. The
      importance of the patency of these bile ducts to bile excretion is illustrated in
      one species of lampreys in which the bile ducts of young ammocoetes become
      infested with larval nematodes to a degree that bile pigment regurgitation into
      the blood results in a green serum that is identified as biliverdin. Despite
      having serum levels of biliverdin that would be toxic to humans, these
      individuals live a complete larval life. The larvae of all lamprey species
      undergo a phase of metamorphosis in which they transform into adults. During this
      phase the larval gallbladder, the bile canaliculi of the hepatocytes, and all the
      intrahepatic bile ducts completely regress in a developmental process called
      lamprey biliary atresia. The epithelium of the extrahepatic common bile duct
      transforms and expands into a caudal portion of the endocrine pancreas of the
      adult. Many of the events of lamprey biliary atresia resemble events occurring
      during experimental and pathological conditions of mammalian cholestasis,
      including disruption to the bile-blood barrier (intercellular junctions),
      accumulation of bile components in the cytoplasmic inclusions, and alteration of
      the distribution of membrane enzymes in hepatocytes. Regression of the bile ducts
      and ductules is accompanied by a periductular fibrosis that seems to be a product
      of activity by lipocytes (Ito cells). The regurgitation of bile products into the
      interstitial tissue of the liver during early biliary atresia may be the stimulus
      for both inflammatory (granulomatous) and autoimmune responses. There are no bile
      ducts in adults lampreys, yet they seem to show no immediate consequences of the
      absence of an exocrine mechanism for the elimination of bile products.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8273516
TI  - Animal models of pigment gallstones.

PMID- 8273517
TI  - Cholesterol cholelithiasis.

PMID- 8273518
TI  - Hepatic cell transplantation.

PMID- 8273519
TI  - Animal models of liver fibrosis.

PMID- 8273520
TI  - Animal models of copper toxicosis.

PMID- 8273521
TI  - Animal models in liver research: iron overload.

PMID- 8273522
TI  - Portosystemic hepatic encephalopathy related with congenital and acquired
      hepatopathies in the dog.

PMID- 8273523
TI  - Metabolic fatty liver of ruminants.

PMID- 8273524
TI  - Avian fatty liver hemorrhagic syndrome: a comparative review.
AB  - Metabolic fatty liver syndromes occur in a variety of species including chickens,
      humans, cows, and cats. Both energy excess and deficit appear to initiate the
      accumulation of liver fat. Although the conditions preceding the onset of liver
      steatosis vary, all syndromes share a common basis in altered lipid utilization,
      lipoprotein assembly, and secretion. Laying hens and humans appear to develop
      fatty livers under similar metabolic conditions of energy excess. This similarity
      and the additional structural requirements inherent in yolk deposition make the
      laying hen an exciting model in which to study lipoprotein synthesis, assembly,
      and secretion. The overfed hen provides additional insights into the effects of
      nutrition and hormones on these same processes. Within this model it may be
      possible to distinguish the effects of altered gene expression versus altered
      physical properties (lipids) and postranslational processing (proteins) in
      mediating the observed responses.

PMID- 8273525
TI  - Physiologic jaundice of the newborn: animal models of perinatal development.

PMID- 8273526
TI  - Animal models of bilirubin encephalopathy.

PMID- 8273527
TI  - Development of reconstructive blepharoplasty: the temporofacial rotation flap.
      Was it first conceived on the Spree, on the Seine, or on the Manzanares?
AB  - The development of reconstructive blepharoplasty in the 19th century is analyzed
      and the techniques classified according to their principles. Besides the main
      contributions of French, German, and Italian plastic surgeons, those made by two
      Spanish surgeons are summarized. Argumosa, who published an article on the
      tempororotation flap two years before Dieffenbach, and Hysern, who developed the
      first musculocutaneous transposition flaps for eyelid reconstruction, are usually
      omitted in the literature. After Dieffenbach's publication, German and French
      surgeons argued about who contributed to the development of plastic surgery in
      general and to blepharoplasty in particular, while in Spain controversies arose
      about the importance of Hysern's and Argumosa's contributions. The background and
      causes of these disputes are analyzed and compared with the present day
      dissemination and publication of new techniques.

PMID- 8273528
TI  - Lower blepharoplasty: partially joined skin and muscle flaps.
AB  - As a method of performing a lower blepharoplasty, the author proposes a partially
      joined skin and muscle flap. This procedure allows one to resect separately
      different amounts of skin and muscle for appropriate correction of the lower-lid
      changes that require an aesthetic blepharoplasty. It also promotes muscle raising
      with consequent skin flap lifting. This technique resects a large amount of skin
      in order to achieve a smoother lower eyelid.

PMID- 8273529
TI  - Abdominal etching: differential liposuction to detail abdominal musculature.
AB  - Male athletes seeking improvement in the detail of their abdominal musculature
      have traditionally utilized vigorous exercise and a tightly controlled diet.
      Abdominal etching is a technique devised to enhance the appearance of the
      abdominal musculature by removing fat with liposuction at variable levels. The
      abdominal musculature is topographically visualized as the linea alba, linea
      semilunaris, and the transverse tendinous intersections within the rectus
      abdominous muscle. These landmarks are enhanced with localized superficial
      liposuction to deepen the natural grooves or furrows in these areas. We have
      performed abdominal etching on eight male patients with good to excellent results
      and minimal risks.

PMID- 8273530
TI  - Direct upper-lip lifting: a safe procedure.
AB  - Thin lips and an aging lower third of the face are increasingly the focus for
      surgical improvement. Thin and tightly pursed lips imply a certain resignation or
      even bitterness, especially in older women. Excessive application of lipstick to
      enhance the shape and color of thin lips was a solution but a poor camouflage.
      The desire for well-defined and full lips, as seen today on many models and
      actresses, is the motivation behind the increasing demand of women with
      relatively normal looking lips to turn to cosmetic surgery. They often present
      the surgeon with photographs of the shape and fullness of lips they desire to
      achieve. In this article the author recommends the use of the direct upper-lip
      lifting method as a more effective and successful approach to enhancing the shape
      of the upper lip. For plumping the lower and upper lip, the author recommends
      using autologous collagen augmentation.

PMID- 8273532
TI  - Application and modification of the circular skin excision and pursestring
      procedures.
AB  - The concept of the circular excision is not new. However, it was complicated by
      excessive postoperative areolar stretching and scar hypertrophy. The Benelli
      principle of a permanent subdermal pursestring suture overcame these drawbacks.
      We present our experiences with the circular skin excision for mastopexy
      procedures and for circular skin incision for total mastectomy and immediate
      reconstruction.

PMID- 8273531
TI  - Propofol-ketamine technique.
AB  - Case reports are presented demonstrating a new, safe, and simple intravenous
      technique for outpatient anesthesia. Vinnik's technique requires hypnotic doses
      of diazepam (Valium) to prevent ketamine-induced hallucinations. The initial
      hypothesis tested in this clinical series was whether hypnotic doses of propofol
      would prevent hallucinations from ketamine as satisfactorily as diazepam. Once
      the initial hypothesis was confirmed, consideration was given to moderating the
      cost of propofol by determining the effect of two levels of midazolam
      premedication on propofol requirements. Hypnotic doses of propofol do prevent
      ketamine-induced hallucinations. It is possible to achieve significant propofol
      savings by premedication with midazolam without compromising patient readiness
      for discharge by the end of the first postoperative hour.

PMID- 8273533
TI  - Periareolar techniques for mammary reduction and elevation.
AB  - Between June 1990 and June 1992 we carried out 56 breast operations: 18
      reductions, 32 mastopexies, and 6 implant changes. The surgical techniques used
      in all cases basically consisted of three phases: the periareolar incision, the
      creation of the superior pedicle with two medial and lateral flaps, and the
      "anchoring," crossed by both flaps in order to hold up the mammary gland. The
      diameter of the "doughnut" of skin that we had to deepidermize varied between 5
      and 15 cm, thus raising the nipple-areola complex by as much as 10 cm. The volume
      of tissue removed from the hypertrophic breast ranged from 70 to 520 g. In 24 of
      the 32 mastopexies, the use of a silicone implant was necessary in order to
      provide greater volume, texture, and better mammary contour. In these cases the
      size of the prostheses varied between 120 and 300 cc. All patients completed the
      postop followup in the normal way. Only three patients suffered a slight
      dehiscence of the periareolar suture, which was solved within a few days of the
      operation by means of a Friedreich. The periareolar cutaneous pleats and the
      hardness of the breast gradually disappeared, as predicted, within a period of 3
      4 months; afterward the breast looked perfectly natural.

PMID- 8273534
TI  - Effect of cortisone on capsular contracture in double-lumen breast implants: ten
      years' experience.
AB  - Two groups of patients are compared with respect to capsular contracture after
      insertion of silicone breast prostheses. Six hundred seventy four women received
      single-lumen gel prostheses and 700 received double-lumen prostheses with
      cortisone. The addition of 12.5 mg of prednisolone to double-lumen prostheses
      diminished capsular contracture (Baker II to IV) dramatically; in patients with
      simple augmentation from 19% to 4.9%, in patients with subcutaneous mastectomy
      from 54% to 14.9%, and in patients with breast reconstruction from 64% to 24.4%.
      The use of double-lumen implants has three distinct advantages: (1) There is no
      bleeding and therefore no contact of the body with the silicone gel. (2) There is
      no danger of ruptured implants, even if the outer shell shows leakage. (3) If
      prednisolone is administered, capsular contracture is prevented to a significant
      degree.

PMID- 8273535
TI  - Saline inflatable prostheses: 14 years' experience.
AB  - This article presents the author's experience with saline implants from 1977
      through 1991. One thousand ninety-one women underwent cosmetic breast
      augmentation during that period. The accumulated surgical data represents the
      collective practice of the author during that period. From 1977 through 1981 all
      implants were placed in the submammary position. From 1982 through 1991 all
      implants were placed in the subpectoral position. The author reviews his
      experience including complications and results. The data supports the conclusion
      that saline implants are an effective, viable alternative to gel-filled implants
      for cosmetic breast augmentation.

PMID- 8273536
TI  - A new biologically, osmotically, and oncotically balanced gel that shows
      calcifications blocked by silicone.
AB  - The radiodensity of silicone gel-filled breast implants is well documented. It
      has been suggested that silicone gel may block the transmission of x-rays
      sufficiently to prevent visualization of microcalcifications that are frequently
      an indicator of malignancy. A new biologically, oncotically balanced gel has been
      developed that has increased radiotranslucency to approximately the density of
      normal breast tissue, increased lubrication qualities, and is quickly and safely
      eliminated by the body should the shell rupture. We present a case wherein a
      patient's mammogram was read as negative two years prior to breast reaugmentation
      due to Baker IV capsular contracture. During surgery, complete calcification of
      the capsule was discovered, as well as two ruptured prostheses; neither condition
      had been detected by the mammogram. These capsules, with their calcifications and
      scar intact, were removed in toto and radiographically compared through standard
      silicone gel-filled breast implants and through implants containing the new
      biologically, osmotically, oncotically balanced gel. The calcifications were
      completely obscured by the silicone gel-filled prosthesis and completely visible
      when viewed through the bio-oncotic gel-filled prosthesis. Postoperative
      mammograms confirmed the radiolucency of the new gel-filled prostheses. This new
      gel appears to be a reasonable alternative to silicone gel for filling breast
      implants.

PMID- 8273537
TI  - Local reaction and migration of injected silicone gel: experimental study.
AB  - A study of the local and migratory effects of free silicone gel taken from a
      mammary prosthesis is reported. Thirty eight Wistar rats were injected in their
      subcutaneous space with 1 cm3 of silicone gel. The animals were sacrificed on
      day: 3, 7, 15, 30, 60, 180, 240, 360, 420, 450. The visceral organs (heart,
      kidneys, lungs, stomach, gonads, liver, pancreas, spleen, intestine), as well as
      the tissue adjacent to the region of injection, were histologically analyzed.
      There was no detectable silicone and no damage to the visceral organs based on
      routine histopathological analysis. The greatest fibrosis was observed at the
      extremities of the disk formed by the silicone in the subcutaneous space.

PMID- 8273539
TI  - Patient satisfaction with reduction mammaplasty: an early survey.
AB  - There is an abundant volume of literature available on the varying techniques of
      reduction mammaplasty, possible complications, and long-term evaluations from the
      surgeon's perspective. However, there is very little to be found on the patient's
      perspective and personal experience with this procedure during the perioperative
      and early postoperative period. This article deliberately concentrates on
      patients' experiences and impressions during the first and second postoperative
      months. A prospective study was undertaken to look at patients' personal
      experiences and satisfaction with different aspects of their reduction
      mammaplasty and their overall satisfaction with the procedure. Thirty-one
      consecutive patients were recruited during a six-month period and evaluated one
      month postoperatively. Twenty-seven of these patients were evaluated again two
      months postoperatively. The overall satisfaction rate was high: 80.6% for the one
      month survey group and 88.9% for the two-month survey group. There was a high
      incidence of minor complications (38%) and a significant number of the patients
      (32.3% of the one-month survey group and 33.3% of the two-month survey group)
      felt the need for more preoperative discussion.

PMID- 8273538
TI  - Clinical experience with the Medpor porous polyethylene implant.
AB  - The Medpor porous polyethylene implant is a highly stable and somewhat flexible
      porous alloplast that has been shown to exhibit rapid tissue ingrowth into its
      pores. A total of 116 Medpor implants were placed in 70 patients over a four-year
      period. Implants were used for the chin, malar area, nasal reconstruction, ear
      reconstruction, orbital reconstruction, and the correction of craniofacial
      contour deformities. Many of these implants were placed in areas long considered
      problematic such as areas of thin soft tissue coverage, extensive scarring, and
      severe facial burns. Nine complications occurred including seven exposures, all
      of which occurred in areas of minimal soft tissue coverage. Because of the rapid
      vascularization of the implants, only two implants were removed, both from the
      columella. On the basis of our results, it is felt that the Medpor implant is an
      excellent alternative to existing implant materials. The implant is easy to
      shape; it is strong yet somewhat flexible; it is remarkably stable; and it
      exhibits tissue ingrowth into its pores.

PMID- 8273540
TI  - Homage to an unknown photographer.
AB  - The Daguerreotype is an integral part of modern history as artifact and witness
      to great events and forms the basis on which the first surgical photograph of an
      amputation was taken in North America, during the Mexican-American War between
      1846 and 1847; however, its photographer remains unknown.

PMID- 8273541
TI  - Coagulation effects of cyclosporine in liver transplantation.
AB  - Thromboembolic complications have been described in graft recipients receiving
      cyclosporine (CS). Whether these individuals have a hypercoagulable state when
      compared to healthy controls was evaluated. Recalcification times (RT) of saline
      incubated citrated whole blood and endotoxin-incubated whole blood of both
      control and transplant patients were determined. There was no difference between
      the RT saline or RT endotoxin groups in both patient groups. These data suggest
      that CS alone has no procoagulant effects, but that additional factors such as
      endotoxin and/or graft-induced antigen production may provoke the thrombotic
      complications.

PMID- 8273542
TI  - Prothrombotic effects of endothelin-2 (ET-2).
AB  - In this report we demonstrate that ET-2, in addition to its powerful
      vasoconstrictor properties and its role in hypertension, is capable of creating a
      hypercoagulable (prothrombotic) state. This study was facilitated by the
      utilization of a sensitive modified recalcification time (MRT) test that can
      measure coagulation at all points in the coagulation spectrum. The MRT was
      determined on aliquots (1 ml) of citrated blood which were added to saline
      (MRTS), to 10 micrograms of endotoxin (MRTE), and to 10 pg of ET-2 (MRT ET-2).
      The mean values of MRTS, MRTE, and MRT ET-2 were 4.3 +/- 0.8, 3.7 +/- 1.0, and
      3.9 +/- 0.8 min, respectively. There was a statistically significant difference
      between MRTE vs. MRTS and MRT ET-2 vs. MRTS using the two-tailed t-test (p < 0.02
      and p < 0.005, respectively).

PMID- 8273543
TI  - Procoagulant property of platelet activating factor (PAF).
AB  - Platelet-activating factor (PAF) is known to activate platelets and thus promote
      clot formation in most mammalian species including humans. In this communication,
      the ability of PAF to hasten the overall coagulation process by measuring the
      recalcification time (RT) is described. Assessment of the RT in vitro indicated
      that the RT was significantly reduced by PAF (p < 0.001). This information adds a
      new dimension to the role of PAF in coagulation and also provides an exciting
      lead to the development of drugs for controlling the state of accelerated
      coagulation by pharmacologic means.

PMID- 8273544
TI  - Impaired activity of thiol-dependent ATPases in rheumatoid mononuclear cell
      membranes.
AB  - Ion-motive ATPase play an essential role in many aspects of cell biology,
      including mononuclear cell (MNC) functions relevant to chronic inflammation. For
      example, ouabain, a specific inhibitor of Na+, K+ ATPase, suppresses both T and B
      cell proliferation but induces synthesis of IL-1. Using a cytochemical assay
      quantified by microdensitometry, total and ouabain-sensitive ATPase activities
      have been compared in MNC from rheumatoid and control subjects. The sensitivity
      of these enzymes to inactivation by thiol-blocking reagents has been studied by
      preincubation with an impermeant SH blocker p-hydroxymercuriphenylsulphonate
      (pHMPSA). The results show that rheumatoid MNC have significantly impaired ATPase
      activity compared to healthy cells and that both total and ouabain-sensitive
      ATPase activities are readily inhibited by pHMPSA. The depressed ATPase activity
      in rheumatoid MNC could thus be due to blockade/oxidation of a reactive surface
      thiol, and could contribute to perpetuation of the chronic inflammatory process
      in these patients.

PMID- 8273545
TI  - The design and synthesis of second generation leukotriene B4 (LTB4) receptor
      antagonists related to SC-41930.
AB  - SC-41930, 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-3,4- dihydro-8-propyl
      2H-1-benzopyran-2-carboxylic acid, is a selective, orally active, LTB4 receptor
      antagonist currently in clinical trials for psoriasis and ulcerative colitis.
      Exhaustive SAR studies found a potential backup compound, SC-50605, which was 7
      16 times more potent than SC-41930 in LTB4 receptor binding, chemotaxis and
      degranulation assays. SC-50605 also inhibited LTB4-induced intradermal chemotaxis
      in cavine skin at an oral dose of 0.10 mg/kg and displayed good activity in
      animal models of colitis and epidermal inflammation both orally and topically.

PMID- 8273546
TI  - Suppressive effects of a novel antioxidant compound on human T cell functions in
      vitro.
AB  - The use of antioxidant compounds with differing modes of action has clearly
      demonstrated involvement of oxidative processes in the activation of T
      lymphocytes. In this paper, we show that a novel antioxidant (lazaroid U75412E, a
      free radical scavenger) suppressed mitogen-induced T cell proliferation in vitro.
      Similar results were obtained with diphenylene iodonium (DPI), a known inhibitor
      of NADPH oxidase. The lazaroid was further shown to inhibit IL 2 production but
      to be less potent in suppressing IL 2 receptor expression. Thus, scavenger-type
      antioxidants act on T cells primarily by blocking a signal necessary for the
      induction of IL 2 synthesis such as the activation of NF kappa B. Furthermore,
      the potent inhibition of lymphocyte responses caused by the specific enzyme
      inhibitor DPI provides direct proof of the source of the oxidants involved in
      these processes.

PMID- 8273547
TI  - Immunomodulatory activity of recombinant IL-1 receptor (IL-1-R) on models of
      experimental rheumatoid arthritis.
AB  - Given the role of IL-1 in inflammation and in autoimmune diseases, studies were
      designed to examine the ability of IL-1 receptor (IL-1-R) to suppress
      inflammation in a model of chronic degenerative joint disease of adjuvant
      arthritis (AA) in Lewis rats and to suppress the development of a systemic lupus
      erythematosus (SLE)-like disease in MRL/lpr mice. IL-1-R was able to prevent the
      onset of the AA and, even if therapy started after the establishment of AA, the
      cytokine receptor was still able to reduce the degree of chronic inflammation and
      arrested its progress. Treating MRL/lpr mice with IL-1-R resulted in a decrease
      in the amount of autoantibodies and inhibited joint inflammation. Even in the
      established disease IL-1-R could reduce rheumatoid factors (RF) and
      autoantibodies, and the signs of a polyarthritis were inhibited.

PMID- 8273548
TI  - Immunoregulation of SLE-like disease by the IL-1 receptor: disease modifying
      activity on BDF1 hybrid mice and MRL autoimmune mice.
AB  - Due to the immunopharmacological profile of the recombinant IL-1 receptor (IL-1
      R) and its potential to modulate biological activity in various inflammatory
      autoimmune disease models, we further elucidated its disease modifying activity
      on the development of a systemic lupus erythematosus (SLE)-like disease in BDF1
      hybrid mice and in MRL/lpr autoimmune mice. Treatment of BDF1 mice with the IL-1
      R during the induction phase resulted in a strong inhibition of the development
      of a glomerulonephritis, prolonged the survival time and improved the survival
      rate. Even a therapeutic effect was demonstrated when this receptor was given
      after the appearance of clinical symptoms. Treating MRL/lpr mice, which develop
      spontaneously a SLE-like disease, with the IL-1-R resulted in an inhibition of
      the developing glomerulonephritis and splenomegaly, in a reduction of swollen
      lymph nodes and in a decrease of autoantibody formation. Even in the established
      autoimmune disease of MRL/1 pr mice the IL-1-R reduced proteinuria, the levels of
      autoantibodies and also improved the survival rate.

PMID- 8273549
TI  - Immunosuppressive therapy of organ-specific nephritic autoimmune diseases with 15
      deoxyspergualin.
AB  - According to its immunopharmacological profile, 15-deoxyspergualin (15-DOS) has
      been investigated as to its disease-modifying activity on HgCl2-induced
      glomerulonephritis (GN) and on tubulointerstitial nephritis (TIN) in Brown-Norway
      rats. Both models are induced autoimmune disorders in which afflicted animals
      display high levels of serum autoantibodies directed against the glomerular or
      tubular basement membrane (GBM or TBM), respectively. The diseases are manifested
      by high serum creatinine and urea levels with severe proteinuria. In the model of
      HgCl2-GN, administration of 15-DOS clearly led to a reduction of proteinuria and
      decreased the amount of rat IgG attached to the GBM. Furthermore, a therapeutic
      effect could be demonstrated when 15-DOS was given after the appearance of
      clinical symptoms. Not only urine-protein values but also anti-laminin antibodies
      returned to normal levels. Also in the experimental TIN-model, 15-DOS, either
      given during the induction phase, or even late in the onset of the disease,
      strongly prevented the proteinuria of this autoimmune disease and inhibited the
      formation of autoantibodies to TBN.

PMID- 8273550
TI  - Additive effects of a bradykinin antagonist, NPC 17761, and a leumedin, NPC
      15669, on survival in animal models of sepsis.
AB  - The effects of coadministration of NPC 17761 (D-Arg-Arg-Pro-Hyp-Gly-Phe-Ser-D
      Hype (transthiophenyl)-Oic-Arg), a potent bradykinin antagonist, and NPC 15669 (N
      [9H-(2,7-dimethylfluoren-9-yl-methoxy)carbonyl]-L-leucine), a leukocyte
      recruitment inhibitor, were examined in rodent models of experimental shock. In
      mice, ED50 doses of NPC 17761 (0.12 mg/kg) and NPC 15669 (4 mg/kg), administered
      together, increased survival (83%) and inhibited leukopenia (60% at 4 h) in
      response to a lethal dose of endotoxin. In rats, independent administration of
      NPC 15669 (10 mg/kg, i.v. bolus) or NPC 17761 (0.1 mg/kg/h, 4 h) did not
      significantly increase survival (36 +/- 4 and 46 +/- 9 h, respectively) versus
      controls (27 +/- 1 h). However, co-treatment essentially "cured" (survival > 1
      week) all septic animals, suggesting synergistic effects of the two agents.

PMID- 8273551
TI  - Human eosinophil major basic protein augments bronchoconstriction induced by
      intravenous agonists in guinea pigs.
AB  - The direct effect of intratracheal (IT) administration of human major basic
      protein (MBP) on pulmonary inspiratory pressure (PIP), and the effect on agonist
      induced change in PIP, were determined in anesthetized, ventilated guinea pigs.
      500 micrograms MBP increased PIP from 24.1 +/- 4.3 to 49.8 +/- 7.4 cmH2O (p <
      0.002, n = 10). Maximum PIP was achieved within 30 min after 500 micrograms MBP.
      The direct PIP response to 250 micrograms MBP was not different from vehicle. The
      PIP responses to intravenous (IV) acetylcholine (Ach) and 5-hydroxytryptamine (5
      HT) were measured before and after administration of 250 micrograms MBP (n = 12).
      MBP caused a modest, but significant potentiation of the increase in PIP induced
      by 1, 3 and 10 micrograms/kg Ach (24, 32 and 28%, respectively, p < 0.02) and to
      1 microgram/kg 5-HT (43% p < 0.02). We conclude that MBP at a dose that does not
      directly affect inspiratory pressure is capable of augmenting the PIP response to
      IV Ach and 5-HT in vivo.

PMID- 8273552
TI  - Effect of the 21-aminosteroid, U-74389F, on hyperoxic lung injury in rats.
AB  - Hyperoxia (> 95% oxygen) in rats caused an increase in lung weight and an
      accumulation of fluid in the thorax. The mean lung wet weight of air-breathing
      controls at 60 h was 1.2 +/- 0.01 g, and that of vehicle-treated, oxygen-exposed
      animals was 2.45 +/- 0.05 g. Treatment with the 21-aminosteroid U-74389F, 3, 10,
      and 30 mg/kg twice daily throughout oxygen exposure, produced 8, 42, and 18%
      inhibition of the oxygen-induced increase in lung weight, respectively. However,
      U-74389F did not inhibit the hyperoxia-induced accumulation of neutrophils in
      bronchoalveolar lavage fluid. No pleural fluid could be aspirated from the thorax
      of air-breathing controls. The volume of pleural fluid in oxygen-exposed, vehicle
      treated animals and animals treated with 3, 10, and 30 mg/kg U-74389F b.i.d. was
      6.5 +/- 0.9, 2.6 +/- 0.6, 0.8 +/- 0.3, and 1.3 +/- 0.5 ml, respectively. U-74389F
      or its biologs are of potential value for the treatment of lung diseases in which
      oxidant damage has been implicated.

PMID- 8273553
TI  - Identification of phospholipase D (PLD) activity in mouse peritoneal macrophages.
AB  - It is now believed that PLD may contribute to the sustained generation of
      diacylglycerol (DAG) within activated cells. DAG can be formed from
      phosphatidylcholine by the sequential actions of PLD and phosphatidic acid
      phosphohydrolase. Phorbal myristate acetate (PMA, 1 microM), A23187 (10 microM)
      or platelet-activating factor (PAF, 100 nM) caused significant enhancement of
      intracellular 14C-phosphatidic acid levels 2-5 min after the addition of
      stimulus, in cultures of peritoneal macrophages pre-labelled with 14C-palmitate.
      Bacterial lipopolysaccharide (LPS) (5 micrograms/ml) or zymosan (375
      micrograms/ml) also stimulated the production of 14C-phosphatidic acid, but over
      a longer time course (15-60 min). In the presence of 1% ethanol each stimulus
      caused significant production of 4C-phosphatidylethanol at the expense of 14C
      phosphatidic acid, thus confirming a contribution of PLD in these reactions. This
      is the first report of PLD activity in this cell type.

PMID- 8273554
TI  - Peptides based on the conserved predomain sequence of matrix metalloproteinases
      inhibit human stromelysin and collagenase.
AB  - Prostromelysin, a member of the family of matrix metalloproteinases, is secreted
      as a zymogen which is activated after cleavage of the His81-Phe82 bond. The 82
      amino acid propeptide that is removed during activation contains 12 amino acids,
      MRKPRC75GVPDVG, that are highly conserved in all MMPs. We evaluated a series of
      peptides that span this region for their ability to inhibit stromelysin. The
      hexapeptide, Ac-RCGVPD, and the pentapeptide, Ac-RCGVP had IC50 values of approx.
      10 microM. The tetrapeptide, Ac-RCGV, was somewhat less potent with an IC50 of 60
      microM. Smaller peptides, e.g. Ac-RCG, were significantly less potent as
      inhibitors. Substitutions of Cys75 with Ser resulted in a complete loss of
      inhibitory activity. The peptides in this series also inhibited human fibroblast
      collagenase.

PMID- 8273555
TI  - Comparison of magnetic resonance imaging (MRI) and histopathology in rabbit
      models of osteoarthritis and immune arthritis.
AB  - Osteoarthritis was surgically induced in mature male Dutch Belted rabbits by
      sectioning the fibular collateral and sesamoid ligaments and removal of the
      anterior horn of the lateral meniscus. The site of surgical intervention was
      detectable by MRI. Histopathologic analysis revealed severe focal cartilage
      lesions on opposing surfaces of the tibia and femur. Histology of cartilage
      adjacent to the osteoarthritic lesions appeared normal. In another animal model,
      arthritis was induced by immunization against ovalbumin followed by intra
      articular injection of ovalbumin. MRI of immune arthritic rabbit knees showed
      accumulation of synovial fluid and cartilage degradation. Histopathology was
      characterized by vascular necrosis of the synovium and depletion of cartilage
      proteoglycan. MRI can be used to non-invasively follow the therapeutic effects of
      drug treatment on synovial inflammation and cartilage degradation in rabbit
      knees.

PMID- 8273556
TI  - Release of cell surface proteoglycan from chondrocytes by interleukin-1.
AB  - A cell culture model was developed to assess factors that can protect cartilage
      from recombinant human interleukin-1 alpha (IL-1)-induced breakdown. IL-1 (0.01
      10 ng/ml) caused a dose-dependent release of cell surface proteoglycan into the
      medium of bovine and rabbit articular chondrocytes. Sulfated glycosaminoglycan (S
      GAG) was detected in the medium and on the cell surface by a dimethlymethylene
      blue assay. The redistribution of the cell surface S-GAG to the medium
      compartment required protein synthesis because it was inhibited by cycloheximide
      and was time-dependent (> 5 h). Although the release was most likely due to de
      novo synthesis of proteases, standard protease inhibitors failed to prevent the
      release even when used in combination. TGF-beta and IGF-I increased the amount of
      S-GAG in both the medium and cell surface compartments, but did not protect from
      IL-1-induced release. This method has an advantage over a cartilage model of IL-1
      induced matrix release because the drug and cytokine exposure time is reduced and
      the variability is less.

PMID- 8273557
TI  - Effect of ETH615, an inhibitor of leukotriene synthesis and IL-8 gene expression,
      on murine dermatoses.
AB  - ETH615 (4-[2-quinolylmethoxy]-N-[3-fluorobenzyl]-phenylaminometh yl-4-benzoic
      acid) is a potent inhibitor of leukotriene biosynthesis in A23187-stimulated
      leukocytes, and of IL-8 gene expression in LPS-stimulated PBMC. It shows anti
      inflammatory activity in a canine model of dermal inflammation. A topical
      formulation is present in phase II clinical trials. In the present study the
      effect of ETH615 on oxazolone-induced acute inflammation and phorbol ester
      induced chronic inflammation in the mouse ear was investigated. Betamethasone
      (0.04 mg/ear) and ETH615 (1-1.5 mg/ear) significantly inhibited both the oedema
      formation and the PMN infiltration. The cream and ointment formulations of ETH615
      developed for clinical studies were equally active. ETH615 is thus an anti
      inflammatory agent in these murine models of dermatosis.

PMID- 8273558
TI  - Anti-inflammatory properties of the protein kinase C inhibitor, 3-[1-[3
      (dimethylamino)propyl]-1H-indol-3-yl]-4-(1H-indol-3-yl)-1H- pyrrole-2,5-dione
      monohydrochloride (GF109203X) in the PMA-mouse ear edema model.
AB  - Protein kinase C (PKC) mediates a number of intracellular signal transduction
      pathways implicated in the pathogenesis of inflammation, including phospholipase
      A2-dependent arachidonic acid release and eicosanoid production. Recent studies
      demonstrate that the PKC inhibitor GF109203X significantly reduces a number of
      inflammatory processes resulting from PKC activation by the topical application
      of phorbol myristate acetate (PMA) to mouse ears. In this model, GF109203X
      significantly reduced edema at doses similar to the PKC inhibitor staurosporine,
      and more effectively than indomethacin, zileuton, or sodium meclofenamate.
      Histological and biochemical analysis of biopsies from control and drug-treated
      ears revealed a marked reduction in edema, infiltrating neutrophils, and levels
      of the neutrophil-specific marker, myeloperoxidase, in GF109203X-treated mice.
      Prostaglandin E2 levels were also reduced in ears treated with GF109203X. These
      data suggest that GF109203X is an effective antiinflammatory agent as evaluated
      in the PMA model of edema, and implicates PKC as a potential target in the
      development of novel anti-inflammatory agents.

PMID- 8273559
TI  - Platelet activating factor modulates peptidoleukotriene effects on the
      permeability of bovine aortic endothelial cell to albumin.
AB  - The purpose of the present experiments was to study the potency of various
      inflammatory mediators to modulate the clearance rate of 125I-albumin through
      bovine aortic endothelial cell (BAEC) monolayer on polycarbonate micropore
      membrane. The incubation of BAEC with LTD4 (10(-8)-10(-6) M) increased dose
      dependently the permeability to radioactive albumin. The effect was potentiated
      by addition of PAF (10(-5) M). LTC4 had a less potent action on the clearance
      rate of 125I-albumin, since only the highest dose of LTC4 used (10(-6) M) had a
      significant effect, and it was not potentiated by PAF (10(-5) M). The treatment
      with PAF alone at concentration up to 10(-5) M did not increase the 125I-albumin
      clearance rate. Our results suggest that BAEC may bear specific receptors for
      LTC4 and LTD4 or that LTC4 is not converted to LTD4 by BAEC. Our results also
      suggest that LTD4 could possibly stimulate the expression of PAF receptors on
      BAEC.

PMID- 8273560
TI  - Mechanisms of skin rashes from fenbufen.
AB  - Fenbufen-induced skin rash was investigated by determining the metabolism of the
      drug to reactive products. At least five lipophilic products (unidentified), the
      active metabolite of this drug, biphenyl acetic acid (BPAA), and a gamma
      hydroxylated derivative (gamma-hydroxy[1,1'-biphenyl]-4-butanoic acid) were
      identified in keratinocytes in vitro and in skin of rats and guinea pigs in vivo.
      The gamma-OH derivatives of BPAA and fenbufen were recovered from papain digests
      of the prior ether-extracted keratinocyte proteins. Fenbufen and its gamma-OH
      metabolite stimulated the production of interleukin-1 from keratinocytes exposed
      to UV radiation but BPAA did not. Inflammatory reactions from fenbufen may
      therefore, arise from production of its metabolites which yield IL-1 upon
      exposure to UV radiation.

PMID- 8273561
TI  - VLA-4-dependent adhesion activities of U937 cells and guinea pig bronchoalveolar
      lavage leukocytes.
AB  - VLA-4-dependent binding to fibronectin (FN) and to a human vascular cell adhesion
      molecule (hVCAM-1)-transfected murine cell line was measured using U937 cells and
      guinea pig (GP) bronchoalveolar lavage (BAL) cells. A species cross-reactive,
      blocking monoclonal antibody directed against human VLA-4 (TY 21.6) inhibited
      U937/FN binding by 71 +/- 7%. The presence of TY21.6 inhibited the stimulated
      binding of U937 cells to hVCAM-1 by 84%. However, TY 21.6 was unable to inhibit
      the BAL/FN binding. With the addition of TY 21.6, the binding of PMA-stimulated
      BAL cells to hVCAM-1 was inhibited by 57 +/- 5%. In summary, human and guinea-pig
      leukocytes express binding activity to both FN and hVCAM-1. A specific VLA-4
      blocking monoclonal antibody, TY 21.6, inhibited U937 and BAL cell binding to
      hVCAM-1, but only inhibited FN binding with U937 cells.

PMID- 8273562
TI  - Pathogenesis of Lactobacillus casei-induced polyarthritis in Lewis rats: 1. Time
      related changes in histopathological scores and hematology.
AB  - Intraperitoneal injection of cell wall fragments from L. casei (ATCC 11578)
      induces an acute and a chronic inflammatory arthritis of the distal joints of
      LEW/N female rats. Histopathological changes in four distal joints and
      hematologic changes were analyzed on days 3, 10, 20, 30, 40, 50 and 59. All
      joints were scored for changes in inflammation, pannus, cartilage and bone. The
      acute inflammatory response consisted of fluid exudate, fibrin, neutrophils and
      some macrophages concentrated along the periosteum of the longer bones. The
      disease progressed with synovial fibroblast proliferation and infiltration of
      lymphocytes and macrophages. On day 10, cartilage changes were associated with
      pannus formation and subchondral fibrosis. Both localized bone resorption and
      periosteal new bone formation were features of the chronic phase. Lymphocytes
      were elevated above normal (p < 0.05) on day 3, 10, 20, 30 and 40; returning to
      the normal range on day 50 and 59. Neutrophils were elevated on days 10, 20, 30,
      40 and 59. L. casei-induced polyarthritis in Lewis rats appears to be a
      fibroblast-, macrophage-mediated disease with a prominent lymphoid component.

PMID- 8273563
TI  - Selective effects of some 5-lipoxygenase inhibitors on synovial interleukin-1 (IL
      1) production compared with IL-1 synthesis inhibitors.
AB  - To determine the role of 5-LO regulation of IL-1 in synovial tissues, we examined
      the effects of 5-LO inhibitors compared with standard IL-1 synthesis inhibitors
      on IL-1 production by human synovial tissue explants from patients with
      inflammatory arthropathies. MK886, L-656,224, PF-5901, and tepoxalin all
      inhibited IL-1 production in concentrations up to 10 microM, whereas other 5-LO
      inhibitors (ICI-211,965, zileuton), as well as IL-1 synthesis inhibitors (IX
      207,887, tenidap), were inactive. LT products, thus regulate IL-1 production and
      inhibition thereof is one strategy for inhibiting this cytokine.

PMID- 8273564
TI  - Characterization of a tight-binding MMP-3 inhibitor using improved fluorescence
      spectroscopy techniques.
AB  - Accurate kinetic characterization of stromelysin (MMP-3) inhibitors is critical
      in the design of potent inhibitors of this enzyme. We have successfully modified
      a previously described assay [1] which used an internally quenched peptide
      substrate (Dnp-PYAYWMR) that, upon cleavage by MMP-3, produces the products, Dnp
      PYA (quiet) and YWMR (a fluorophore at 360 nm). This improved assay uses purified
      human MMP-3 in the presence of either 5% methanol or 5% DMSO. Fluorescence
      intensities associated with total hydrolysis of substrate by enzyme have been
      successfully mimicked using a combination of the product peptides as a standard.
      We have determined a Km of 39.2 microM and Kcat/Km of 4.6 microM/h for MMP-3 (in
      5% MeOH) using this peptide substrate. This assay was used successfully to
      characterize Ro 31-4724 ((N-[(N-[2-[(N-hydroxycarbamoyl)methyl]-4-methyl-valeryl]
      L-leucyl ] - L-alanine ethyl ester) as a reversible, tightly binding, inhibitor
      with a Ki of 26 nm.

PMID- 8273565
TI  - Sublethal doses of exogenous hydrogen peroxide prime human neutrophils to formyl
      peptide.
AB  - Hydrogen peroxide (H2O2) is an oxidative agent important in inflammation and
      ischemia. Neutrophils (PMNs) are a main source of H2O2 in the inflammatory focus.
      However, after recruitment into the inflammatory or ischemic zone of the heart,
      the PMN itself might serve as a target for exogenous H2O2. In the present work we
      found that PMNs are very resistant to the cytotoxic action of H2O2 (LD50 for PMNs
      is about 30-50 mM, whereas for endothelial cells it is about 200-300 microM).
      Unexpectedly, treatment of PMNs by H2O2 at a sublethal dose of 10 mM leads to a
      subsequent increase in the generation of superoxide anion in response to the
      chemoattractant peptide FMLP (twofold increase in O2- generation 30 min after
      treatment by H2O2 as compared with nontreated control cells). H2O2 itself does
      not induce O2- generation by PMNs. Therefore, any H2O2 that accumulated in the
      inflammatory or ischemic zone might alter the functional activity of PMNs and
      prime them to subsequent agonist activation.

PMID- 8273566
TI  - Differential antagonism of platelet activating factor-induced neutrophilia and
      gastric hemorrhage in the rat.
AB  - Intravenous injection of platelet activating factor (PAF) in rats produced
      hypotension, neutrophilia, gastric congestion, and sloughing of the gastric
      epithelium. The congestion was quantified by measuring hemoglobin in the gastric
      mucosa. Other lesions were quantified by scores of gross pathology and
      histopathology. PAF-induced changes in neutrophil levels were prevented by
      pretreatment with the PAF-antagonist Ro24-4736, but not by the PAF-antagonist CV
      3988. Both PAF antagonists reduced the hypotension, the amount of hemoglobin in
      the gastric mucosa, and the PAF-induced gastric pathology. These results suggest
      that PAF receptors involved in PAF-induced neutrophil mobilization respond
      differently from PAF receptors in the gastrointestinal and cardiovascular
      systems.

PMID- 8273567
TI  - Pathogenesis of Lactobacillus casei-induced polyarthritis in Lewis rats: 2. Time
      related changes in organ weights and liver enzymes.
AB  - Hepatic enzymes and organ weights were measured in LEW/N female rats during the
      acute and the chronic phases of L. casei-induced arthritis on day 3 and days 30
      and 59, respectively. In the acute phase, day 3, adrenal and spleen weights were
      increased and thymus weights were decreased in L. casei arthritic rats as
      compared to normal control rats. Adrenal, liver, kidney, spleen and thymus
      weights of arthritic rats were in the normal range on days 30 and 59. Liver
      cytochrome P450, aminopyrine N-demethylase and analine hydroxylase were reduced
      in livers of L. casei-treated rats on day 3 as compared to normal controls. On
      days 30 and 59 hepatic enzymes in L. casei-arthritic rats were in the normal
      range. Unlike adjuvant arthritis in which changes in liver enzymes alter drug
      metabolism; after the acute onset of L. casei-induced arthritis, hepatic enzymes
      return to the normal range.

PMID- 8273568
TI  - The pharmacologic evaluation of locomotor activity versus inflammatory parameters
      in rat adjuvant arthritis.
AB  - Adjuvant-induced arthritis (AA) is an experimental model of inflammatory joint
      disease in the rat which mimics rheumatoid arthritis. Although paw inflammation
      (e.g., swelling) is commonly used to monitor the efficacy of antiarthritic drugs,
      a reduction in locomotor function may provide a more sensitive evaluation of
      "functional disability" in AA rats. The purpose of the present study was to
      investigate the effect of dietary therapy with prednisolone or ibuprofen on
      locomotor activity as well as arthritic symptoms in established AA (days 20-42).
      AA rats demonstrated an increase in arthritis scores, spleen weights, fibrinogen,
      and WBC along with a reduction in locomotor function. Prednisolone (2 mg/kg/day)
      exhibited a positive therapeutic effect on all these parameters. Ibuprofen (50
      mg/kg/day) consistently lowered arthritis scores and fibrinogen; however,
      locomotor function only improved on day 35. In conclusion, the measurement of
      locomotor activity in concert with other experimental parameters may provide a
      more meaningful evaluation of disease severity or improvement in AA.

PMID- 8273569
TI  - Studies on the effects of an ornithine decarboxylase inhibitor on lupus nephritis
      reveal a post-transcriptional modification of the enzyme.
AB  - Upregulation of ornithine decarboxylase (ODC) activity and polyamine levels is
      found in the kidney of MRL-lpr/lpr (lpr) mouse, an animal model of lupus. To
      understand the molecular genetics of ODC regulation in lpr mouse, we analyzed ODC
      mRNA and activity in the kidney of lpr and normal BALB/c and MRL(-)+/+ mice.
      Although ODC activity was significantly higher in lpr kidney, its mRNA level was
      lower compared to normal strains, as measured by Northern blot hybridization.
      Treatment of lpr mouse with difluoromethylornithine (DFMO) reduced ODC activity
      in lpr kidney to the level of normal strains. In contrast, ODC mRNA level
      increased 12-fold by DFMO treatment. These results suggest that post
      transcriptional modification of ODC in lpr genetic background might be
      responsible for increased ODC activity and polyamines. The beneficial effect of
      DFMO on murine lupus suggests a pathogenic role for altered ODC regulation in lpr
      mouse.

PMID- 8273570
TI  - Structural characterization of BPI-modulating 15 kDa proteins from rabbit
      polymorphonuclear leukocytes: identification of a novel family of leukocyte
      proteins.
AB  - We have previously described the isolation and initial characterization of 15 kDa
      protein isoforms (p15s) from rabbit polymorphonuclear leukocytes (PMN) that bind
      to Escherichia coli and modulate the antibacterial actions of other leukocyte
      proteins on this gram negative organism. We now report that the p15s differ in
      primary structure. The cloning and sequencing of two distinct p15 cDNAs from a
      rabbit bone marrow library reveal that two of the isoforms are closely similar in
      primary structure differing at only two amino acid positions. The p15 cDNAs
      encode putative signal sequences suggesting a granule-associated localization for
      these proteins. Analysis of the derived p15 primary structures reveals homology
      to two leukocyte proteins: CAP-18, an 18 kD lipopolysaccharide (LPS) binding
      protein from rabbit PMN and cathelin, an 11 kD cysteine protease inhibitor from
      porcine leukocytes. This structural similarity suggests the existence of a novel
      family of low molecular weight leukocyte proteins with potential roles in
      inflammation.

PMID- 8273571
TI  - Effects of chronic NSAIDs on gastric mucosal injury related to mucosal
      prostanoids, and plasma drug concentrations in human volunteers.
AB  - The relationship between endoscopically observed gastric mucosal damage, elicited
      following repeated oral intake for 7 d of four NSAIDs, to their effects on antral
      and fundic production of PGE2, 6-keto-PGF1 alpha and TxB2 (assayed by GC-MS),
      mucosal histology and plasma concentration profiles was studied in 40 normal
      males. Subjects received azapropazone (APZ) 600 mg b.i.d., indomethacin (IND) 50
      mg t.i.d., naproxen (NAP) 500 mg b.i.d., piroxicam (PIR) 20 mg qq.d., or one
      placebo capsule t.i.d. (N = 8/group). Plasma NSAIDs (HPLC) levelled at 7 d.
      Mucosal damage occurred in the antrum region with IND and NAP. APZ and PIR
      exhibited no differences compared to placebo. NAP and IND reduced all three
      prostanoids in the antrum while APZ and PIR were ineffective. Fundic PGE2 was
      reduced by IND, NAP and PIR; APZ had no effects. Thus, mucosal damage relates to
      effects on prostanoid production in the antrum but not in the fundus.

PMID- 8273572
TI  - Modulation of cartilage destruction in murine arthritis with anti-IL-1
      antibodies.
AB  - One of the early events in murine antigen-induced arthritis is the generation of
      IL-1 in the inflamed joint. We investigated the role of IL-1 in the acute phase
      of the arthritic process by selective blockage of IL-1 bioactivity by treatment
      with neutralizing antibodies. Pretreatment with anti-IL-1 antibodies moderately
      suppressed joint swelling. The decrease in chondrocyte proteoglycan synthesis
      seen in the acute phase of arthritis was prevented by treatment with anti-IL-1
      antibodies. IL-1 does not appear to be a major contributor to the accelerated
      breakdown of articular cartilage in this model. The major impact of anti-IL-1
      antibodies was the prevention of proteoglycan synthesis inhibition which clearly
      reduced articular cartilage depletion by maintaining normal proteoglycan
      synthesis.

PMID- 8273573
TI  - The role of AP-1 in matrix metalloproteinase gene expression.
AB  - In an effort to understand the mechanism of matrix metalloproteinase (MMP)
      induction, lapine synoviocytes were isolated and incubated with phorbol myristate
      acetate (PMA) and autocrine "cell-activating factors" (CAF), agents which
      significantly increase MMP mRNA abundance. AP-1 complexes, formed by c-fos and c
      jun which bind to 5' residues of the MMP genes, seem causally related to MMP gene
      expression in response to PMA. However, although AP-1 DNA binding activity is
      strongly induced following exposure of synoviocytes to CAF, MMP gene expression
      in response to CAF does not correlate well with AP-1 activity and is not
      inhibited by antisense DNA to fos and jun. We hypothesize that there is a CAF
      response factor involved in MMP gene expression and that this factor competes
      with the binding of the AP-1 complex to its target response element.

PMID- 8273574
TI  - Cysteine proteinase activity in the development of arthritis in an adjuvant model
      of the rat.
AB  - Cathepsin B and L activity was studied histochemically in arthritic rat ankle
      joints using specific synthetic substrates in a post coupling method on unfixed
      and undecalcified cryostat sections of rat ankle joints. Activity was strongly
      increased in chondrocytes and cells of the inflamed synovium with the development
      of arthritis induced by the synthetic adjuvant CP20961. Activity reached a
      maximum 20 days after induction of arthritis and decreased as the rats entered
      natural remission. Cathepsin B and L were at their highest level when macrophages
      were present in the joint space, as shown by using monoclonal antibody markers
      for rat macrophages (ED1 and ED2) in a biotin-avidin immunoperoxidase assay. This
      suggests that the macrophage infiltrate may have stimulated proteinase production
      in chondrocytes through cytokine release. The profile of appearance of cysteine
      proteinases suggests their involvement in the breakdown of cartilage and bone in
      the arthritic joint.

PMID- 8273575
TI  - Leukotrienes in the pathogenesis of NSAID-induced gastric and intestinal mucosal
      damage.
AB  - Studies in pigs and rats were undertaken to explore further the role of
      leukotrienes following administration of NSAIDs on the development of
      gastrointestinal damage. Increased leukotriene C4 production occurred in the
      gastric circulation in the early stages after administration of a single dose of
      indomethacin (10 mg/kg i.g.) to pigs. Gastric and intestinal mucosal lesions by
      NSAIDs were prevented by both prior (2-5 h)+ 0.25 or 0h oral dosing of the 5
      lipoxygenase inhibitor, MK-886, but not when only one of these doses was given.
      These results show the importance of enhanced peptidoleukotriene production in
      relation to microvascular damage from cyclooxygenase inhibition by NSAIDs.

PMID- 8273576
TI  - Analgesic activities of PEM-420, the active eutomer of pemedolac.
AB  - PEM-420, the active isomer of pemedolac, inhibited the writhing responses induced
      by phenylbenzoquinone (PBQ), acetic acid, and acetylcholine in mice with ED50's
      of 0.80, 0.92, and 0.075 mg/kg p.o., respectively. In the rat acetic acid
      writhing assay, PEM-420 exhibited an ED50 value of 8.4 mg/kg p.o. In the Randall
      Selitto test, PEM-420 raised the pain threshold of the yeast-injected paw (ED50 =
      0.55 mg/kg p.o.). Like other NSAIDs, PEM-420 inhibited the PBQ-induced production
      of PGI2 and PGE2 in the mouse peritoneal cavity, with ED50 values of 0.5 and 1.2
      mg/kg p.o., respectively. It had weak ulcerogenic liability in rats (acute UD50 =
      99 mg/kg p.o. in fasted rats; subacute UD50 = 74 mg/kg/day for 4 days in fed
      rats). The data indicate that PEM-420 is a potent and safe peripheral analgesic.

PMID- 8273578
TI  - Structure-activity relationships leading to WAY-121,520, a tris aryl-type,
      indomethacin-based, phospholipase A2 (PLA2)/leukotriene biosynthesis inhibitor.
AB  - We were intrigued by reports of the inhibition of phospholipase A2 (PLA2) by
      indomethacin. In order to increase the potency of the indomethacin system as an
      inhibitor of PLA2, it was decided to make more lipophilic analogs. Indeed,
      covalent attachment of a quinoline ring to the methoxy substituent of
      indomethacin affords WAY-122,220 which is almost an order of magnitude more
      potent than indomethacin in inhibiting human synovial fluid PLA2 (IC50 = 15 and
      145 microM, respectively). The N-p-chloro-benzyl analog of this compound, WAY
      121,520, was an even more potent inhibitor of PLA2 (IC50 = 4 microM). Structural
      analyses and molecular modeling suggest that these compounds may inhibit PLA2 by
      mimicking arachidonic acid. WAY-121,520 is also a potent leukotriene biosynthesis
      inhibitor both in the rat PMN and mouse macrophage assays (IC50 = 10 and 4 nM,
      respectively), possibly acting via a 5-LO (5-lipoxygenase) translocation
      inhibition mechanism. The multiple actions of WAY-121,520 may contribute to its
      favorable anti-inflammatory profile.

PMID- 8273577
TI  - Pharmacological characterization of WAY-121,520: a potent anti-inflammatory
      indomethacin-based inhibitor of 5-lipoxygenase (5-LO)/phospholipase A2 (PLA2).
AB  - WAY-121,520 inhibited human synovial fluid PLA2 (HSF-PLA2) (IC50 = 4 microM)
      using arachidonic acid-labeled E. coli as substrate. Further biochemical
      characterization of WAY-121,520 demonstrated potent inhibition of 5-lipoxygenase
      (5-LO) activity in the murine macrophage (LTC4, IC50 = 4 nM) and rat PMN (LTB4,
      IC50 = 10 nM) and an ability to antagonize LTD4 binding to isolated guinea-pig
      trachea (pKB = 6.0). In vivo anti-inflammatory activity was noted in murine TPA
      induced (ED50 = 91 micrograms/ear) and arachidonic acid-induced (66% inhibition
      at 400 micrograms/ear) ear edema and in leukotriene-dependent antigen-induced
      bronchoconstriction in the guinea pig (73% inhibition at 50 mg/kg, p.o.). WAY
      121,520 represents a novel series of indomethacin-based inhibitors of PLA2 with
      anti-inflammatory activity resulting from a combination of biochemical activities
      (inhibition of 5-LO and PLA2 and LTD4 antagonism). This agent may provide added
      therapeutic efficacy over more selective inhibitors.

PMID- 8273579
TI  - Anti-colitic efficacy of SC-41930 in colitic cotton-top tamarins.
AB  - To evaluate anti-colitic efficacy, eight cotton-top tamarins (CTTs) with
      histologically confirmed persistent active colitis were given the anti
      inflammatory agent SC-41930 (10 mg/kg BW by gavage BID) for eight weeks. Colonic
      endoscopy and biopsy observations, CBCs and clinical chemistries, and stool
      consistency were evaluated pre-, mid-, and posttreatment. Colitic activity was
      graded histologically from A1 (mild) to A5 (severe); results varied among the
      seven animals that completed the study: five improved, one worsened, and one was
      unchanged. Serum enzyme levels were significantly reduced with treatment. Stool
      condition remained puddly throughout treatment and body weights did not vary from
      pretreatment levels. However, SC-41930 produced histological evidence (reduced
      numbers of polymorphonuclear cells) of anti-colitic efficacy over an eight-week
      treatment period in CTTs with persistent active colitis. These results support
      the use of the CTT colitis model to evaluate efficacy of therapeutic agents and
      provide useful predictive information to aid in the medical management of human
      IBD.

PMID- 8273580
TI  - Secretory phospholipase A2 inhibitors and calmodulin antagonists as inhibitors of
      cytosolic phospholipase A2.
AB  - Human cytosolic phospholipase A2 (cPLA2, 85 kDa) appears to be pharmacologically
      distinct from human secretory phospholipase A2 (sPLA2, 14 kDa). Marine natural
      products and PLA2 substrate and product analogs were potent inhibitors of human
      recombinant sPLA2 (r-sPLA2), whereas these compounds stimulated, weakly
      inhibited, or had no effect on cPLA2 activity from the human monocytic cell line
      U937. In contrast, within a series of seven reported calmodulin (CaM) antagonists
      tested, significant correlations among the rank order of potencies of these
      compounds as inhibitors of cPLA2, r-sPLA2, and a CaM-dependent phosphodiesterase
      were observed. The correlated inhibitory effects of the hydrophobic CaM
      antagonists on cPLA2 and sPLA2 may reflect a common feature (possibly a
      hydrophobic domain) shared by these two types of enzymes.

PMID- 8273581
TI  - Effect of 5-lipoxygenase inhibitors on in situ LTB4 biosynthesis following
      calcium ionophore stimulation in the rat pleural cavity.
AB  - The intrapleural injection of carrageenan in the rat induces exudate formation,
      cellular influx and leukotriene generation in the pleural cavity. We have
      demonstrated that the inflammatory response (exudate volume, and LTB4 levels) is
      increased in situ by the intrapleural administration of calcium ionophore A 23187
      (100 nmol/rat) at 4, 16, 24, 48, and 72 h after the injection of carrageenan and
      that the A 23187-induced increase is dose-dependent. The oral administration of A
      64077 and MK-886, two 5-lipoxygenase inhibitors (5-LOIs), at 10 mg/kg causes
      marked decreases in LTB4 release at the above-mentioned time intervals. However,
      A 23187-induced augmented exudate formation is not affected by the treatment with
      5-LOIs. The results suggest that the use of 5-LOIs to inhibit LTB4 biosynthesis
      may be beneficial in various LTB4-dependent pathological conditions.

PMID- 8273582
TI  - Effect of anti-inflammatory compounds on edema formation and myeloperoxidase
      activity in the arachidonic acid-induced ear model in the mouse.
AB  - The arachidonic acid (AA)-induced ear edema model in the mouse has been
      demonstrated as an effective in vivo experimental tool to screen compounds
      showing anti-inflammatory activity. Since neutrophil influx is a component of the
      inflammatory reaction, we have modified this assay by quantitating
      myeloperoxidase (MPO) levels which reflect neutrophil accumulation in the
      edematous biopsies of the mouse ear. Our work has shown that orally administered
      5-lipoxygenase inhibitors, dual inhibitors (CO/LO), and steroids dose-dependently
      inhibit both edema formation and MPO activity, whereas oral activity is not seen
      with NSAID's. There is a good correlation between the inhibition of edema
      formation and of MPO activity by these compounds. Thus, measurement of MPO, in
      addition to the AA-induced edema in the mouse ear, can provide another parameter
      to profile potential anti-inflammatory compounds.

PMID- 8273583
TI  - Anti-inflammatory properties and inhibition of leukotriene C4 biosynthesis in
      vitro by flavonoid baicalein from Scutellaria baicalensis georgy roots.
AB  - Anti-inflammatory activity of baicalein (5,6,7-trioxyflavone-7-O-beta-D
      glucuronide) was greater in the chronic inflammation model (rat adjuvant
      arthritis, ED50 = 120.6 mg/kg) than observed in the rat carrageenan-induced paw
      edema, ED50 > or = 200.0 mg/kg. A comparative study of the 5-lipoxygenase (5-LO)
      inhibitory activity of baicalein, BW 755 C, and hydroxamic acid arachidonate on
      leukotriene C4 (LTC4) biosynthesis by rat resident peritoneal macrophages
      stimulated with calcium ionophore (A 23186) showed that these drugs significantly
      inhibited LTC4 production, IC50: 9.5, 41.8, and 2.8 microM, respectively. This
      finding suggests that inhibition of the 5-LO pathway of arachidonic acid
      metabolism may be one of the mechanisms of baicalein's anti-inflammatory
      activity.

PMID- 8273584
TI  - Interleukin-1 beta induces cytosolic PLA2 in parallel with prostaglandin E2 in
      rheumatoid synovial fibroblasts.
AB  - We investigated the temporal relationship between the increase in enzymatic
      activity and protein of a high molecular weight (100 kDa), cytosolic PLA2 (cPLA2)
      in interleukin-1 beta (IL-1 beta)-treated rheumatoid synovial fibroblasts (RSF).
      Both of these responses increased according to a similar time-course which
      correlates with PGE2 production by these cells. In contrast, 14 kDa, secreted
      PLA2 (sPLA2), which was also produced by RSF, was not affected by IL-1 beta
      treatment. These findings support that an augmentation of CPLA2 activity, caused
      by an induction of cPLA2 protein, rather than sPLA2, is temporally associated
      with increased PGE2 production in IL-1 beta-treated RSF.

PMID- 8273585
TI  - Inhibition of endotoxin-induced hypothermia and serum TNF-alpha levels in CD-1
      mice by various pharmacological agents.
AB  - Intraperitoneal injection of lipopolysaccharide (LPS) was used to elicit a
      sublethal, shock-like condition in mice. LPS, 2.5 mg/kg i.p., induced
      hypothermia, elevated serum TNF-alpha levels and lethality over a 48 h period in
      male CD-1 mice. The 5-lipoxygenase (LO) inhibitors, WY-50,295 tromethamine and
      zileuton (100 mg/kg p.o), significantly inhibited hypothermia at 4, 24 and 48 h
      after LPS. Interestingly, whereas cyclooxygenase (CO) inhibitors (ibuprofen,
      etodolac, naproxen and tenidap) at 40-80 mg/kg p.o. stimulated hypothermia at 4
      h, they significantly reduced the later stages of hypothermia at 24-48 h.
      Rolipram (PDE-IV inhibitor) and dexamethasone significantly reduced hypothermia
      at 4-24 h and 1-24 h, respectively. All the anti-inflammatory agents
      significantly reduced elevated TNF-alpha levels at approximately 70 min post-LPS,
      except for ibuprofen. In conclusion, these anti-inflammatory standards indicate
      that LPS-induced shock involves multiple lipid mediators (PG's, LT's and possibly
      PAF) and secondary cytokine generation. This sublethal model of LPS-induced shock
      represents a sensitive model for estimating the efficacy of potential drug
      candidates for the treatment of endotoxic shock.

PMID- 8273586
TI  - Effects of pyridinyl imidazole compounds on murine TNF-alpha production.
AB  - The effects of SK&F 86002 and other pyridinyl imidazole compounds on murine
      cytokine production were investigated. In vitro, SK&F 86002 inhibited LPS
      stimulated TNF-alpha production by the RAW 264.7 cell line and by oil elicited
      peritoneal macrophages with an IC50 of 5 microM. In general, the activity was
      reflective of previous results obtained with human monocytes as SK&F 86002 and
      its analogs demonstrated identical rank order potency for TNF-alpha inhibition in
      both species. These compounds also inhibited TNF-alpha in vivo in a murine model
      of endotoxin shock. Following oral administration, SK&F 86002 and its analogs
      reduced serum TNF-alpha levels by > 80% and afforded 100% protection from
      lethality. In contrast, tenidap, a novel anti-inflammatory drug, had minimal to
      no effect on murine TNF-alpha production in the same assays. These data further
      extend the pharmacological profile of the pyridinyl imidazoles by demonstrating
      that these compounds potently inhibit murine TNF-alpha production both in vitro
      and in vivo.

PMID- 8273587
TI  - Adjuvant arthritic (AA) rats exhibit enhanced endotoxin-induced plasma TNF (EIPT)
      levels.
AB  - Adjuvant arthritis (AA) was induced in male Lewis rats by a single FCA (M.
      butyricum) injection into the tail. At various time periods post FCA injection,
      AA and control rats were anesthetized and administered E. coli endotoxin (30
      mg/kg, i.v.). Plasma samples were obtained at 30, 60, 90, 120 and 150 min
      following endotoxin administration and assayed for TNF alpha levels by ELISA.
      Compared to control rats, AA rats exhibited enhanced EIPT levels (706% of
      control, p < 0.05) which was associated with the onset of inflammatory lesions on
      days 12-14 post FCA, and remained significantly elevated (> 300% of control, p >
      0.05) for at least 30 days post FCA. There were no significant correlations
      between EIPT levels and hindpaw volumes or body weights. The results of this
      study support previous observations that AA is associated with macrophage
      activation and suggest that EIPT levels in AA rats may be a useful parameter for
      the evaluation of novel antiarthritic agents.

PMID- 8273588
TI  - Tumour necrosis factor alpha production by rat blood and its ex vivo
      pharmacological modulation.
AB  - Rat blood was investigated as a suitable test system for the discovery of
      inhibitors of tumour necrosis factor alpha (TNF alpha) biosynthesis.
      Lipopolysaccharide (LPS) caused a concentration- and time-dependent stimulation
      of TNF alpha production by heparinised rat blood with peak levels (1000-5000
      U/ml; L929 bioassay) at 6 h. Bioactive material was neutralised with a polyclonal
      rabbit anti-murine TNF alpha antibody which cross-reacts with rat TNF alpha.
      Dexamethasone, pentoxifylline and denbufylline inhibited TNF alpha production
      with IC50s of 6.0 +/- 2.0 nM, 20.6 +/- 8.00 microM and 138.0 nM, respectively.
      When rats were dosed p.o. with dexamethasone or pentoxifylline or i.p. with
      denbufylline and 1.5 h later TNF alpha production was assessed ex vivo by LPS
      stimulated blood, a dose-related inhibition of TNF alpha production occurred with
      ID50s of approximately 0.08, 250.0 and 5.0 mg/kg, respectively. These results
      demonstrate that rat blood provides a useful test system for the detection and ex
      vivo evaluation of inhibitors of TNF alpha biosynthesis.

PMID- 8273589
TI  - Pyridinyl imidazoles inhibit IL-1 and TNF production at the protein level.
AB  - The mechanism by which SK&F 86002 and other pyridinyl imidazoles inhibit the
      production of IL-1 and TNF from LPS-stimulated human monocytes was examined.
      Inhibition of IL-1 and TNF production was found to depend on the time of addition
      of SK&F 86002, with diminishing effect when added more than 2 h after LPS
      stimulation. Analysis of Western blots confirmed that both intracellular IL-1
      beta and extracellular TNF were significantly reduced in response to SK&F 86002,
      but these reductions were not paralleled by changes in IL-1 and TNF mRNA. 35S
      methionine pulse and pulse-chase studies on IL-1 biosynthesis suggest that
      significant inhibition by SK&F 86002 and related compounds occurs at the
      translational level.

PMID- 8273590
TI  - The effects of anti-inflammatory and antiallergic drugs on the release of IL-1
      beta and TNF-alpha in the human whole blood assay.
AB  - Heparinized human whole blood was evaluated as a model to study the effects of
      various classes of anti-inflammatory drugs on IL-1 beta and TNF-alpha release
      from leukocytes. Human whole blood was stimulated with zymosan (1.5 mg/ml) or LPS
      (5 micrograms/ml) to induce significant cytokine release. As previously reported,
      the 5-lipoxygenase/cyclooxygenase (5-LO/CO) inhibitor, SKF86002 (30 microM),
      significantly inhibited both IL-1 beta and TNF-alpha release using either
      stimulus. In contrast, the cyclooxygenase (CO) inhibitors (naproxen and
      ibuprofen) and the lipoxygenase (5-LO) inhibitors (zileuton, L-663536 and BWA4C)
      did not effect IL-1 beta or TNF-alpha release/biosynthesis. Isoproterenol (beta
      agonist), rolipram (a PDE-IV inhibitor), and IBMX (a nonselective PDE inhibitor),
      significantly inhibited TNF-alpha but not IL-1 beta in the LPS model while having
      no effect in the zymosan model. This human whole blood assay is a unique and
      rapid method which can be used to identify novel inhibitors of IL-1 beta and TNF
      alpha release/biosynthesis.

PMID- 8273591
TI  - Effect of protein kinase inhibitors on IL-8/NAP-1 release from human umbilical
      vein endothelial cells.
AB  - Several protein kinase inhibitors (PKIs) were investigated for their effects on
      IL-1 beta, TNF alpha and PMA-induced IL-8 production from human umbilical vein
      endothelial cells (HUVEC). IL-1 beta (ED50 0.07 ng/ml), TNF alpha (ED50 100
      ng/ml) and PMA (ED50 20 ng/ml) induced IL-8 production that could be detected as
      early as 2 h following stimulation. Staurosporine, a potent but non-specific
      inhibitor of protein kinases, inhibited PMA-induced (IC50 2 nM) but not IL-1 beta
      or TNF alpha (IC50 > 200 nM) induced IL-8 production. Neither the cAMP-dependent
      PKI, KT5720, nor the tyrosine PKIs, genistein, tyrphostin (1-100 microM) or
      lavendustin A (0.0001-1 microM), inhibited IL-8 production elicited by IL-1 beta.
      However, the macrolide protein kinase inhibitor geldanamycin (IC50 = 30 nM), but
      not the closely related analog herbimycin A (5-500 nM), inhibited IL-8 production
      by 60%. Northern blot analysis of IL-8 mRNA revealed that staurosporine
      suppressed mRNA increase following stimulation by PMA but not by IL-1. It is
      proposed that a novel protein kinase susceptible to geldanamycin inhibition may
      be involved in IL-1-mediated signal transduction.

PMID- 8273592
TI  - Modulation of TNF alpha and IL-1 beta from endotoxin-stimulated monocytes by
      selective PDE isozyme inhibitors.
AB  - The effect of selective PDE isozyme inhibitors including vinpocetine (PDE-I), CI
      930 and milrinone (PDE-III), rolipram and nitraquazone (PDE-IV) and zaprinast
      (PDE-V) on monocyte viability and production of tumor necrosis factor (TNF alpha)
      and interleukin-1 beta (IL-1 beta) elicited from endotoxin-stimulated human
      monocytes was investigated. None of the inhibitors affected monocyte viability at
      10 microM or lower concentrations. PDE-IV inhibitors and to a lesser extent, PDE
      III inhibitors suppressed TNF alpha production. Only high concentrations of PDE
      IV inhibitors modestly suppressed IL-1 beta. Zaprinast stimulated IL-1 beta and
      to a lesser extent TNF alpha production. These data show that TNF alpha and IL-1
      beta production are differentially regulated, and that PDE III, PDE-IV and PDE-V
      isozymes are functional in endotoxin-stimulated monocytes. Clinical trials will
      be needed to ascertain if PDE-IV inhibitors are able to suppress TNF alpha levels
      in man.

PMID- 8273593
TI  - Inflammatory mediator changes in cotton-top tamarins (CTT) after SC-41930 anti
      colitic therapy.
AB  - Use of the CTT model provides insight into the inflammatory mediator contribution
      in the pathogenesis of idiopathic colitis. To evaluate anti-colitic efficacy, the
      leukotriene B4 receptor antagonist and anti-inflammatory agent, SC-41930, was
      administered (10 mg/kg BW by gavage BID) for 8 weeks to CTTs with histologically
      confirmed persistent and defined active colitis. The inflammatory mediators LTB4,
      PGE2, TXB2, and PAF were assayed in colonic dialysate that was collected after 1
      1/2 h from four CTTs pre-, mid-, and post-treatment, frozen at -70 degrees C, and
      analyzed by RIA after HPLC purification. LTB4 levels were lower at mid- and post
      treatment and had little inter-animal variation post-treatment. PGE2 and PAF
      levels were elevated during SC-41930 treatment, but there was a trend towards
      lower thromboxane B2 levels. Reduced LTB4 (PMN degranulation and chemotaxis) and
      increased PGE2 (mucosal-protective effect) may, in part, explain the observed
      efficacy of SC-41930 in active tamarin colitis.

PMID- 8273594
TI  - The leukocyte recruitment inhibitor, NPC 15669 accelerates healing in acetic acid
      induced colitis.
AB  - The therapeutic efficacy of the leukocyte recruitment inhibitor, NPC 15669 (N-[9H
      (2,7-dimethylfluoren-9-yl-methoxy)carbonyl]-L-leucine), was evaluated through the
      time course of acetic acid colitis in rats. Intrarectal (i.r.) administration of
      dilute acetic acid produced intense inflammation of the colon, neutrophil
      infiltration, hemorrhage, necrosis and denuding of epithelium. Myeloperoxidase
      (MPO) accumulation increased approximately 40-fold (by day 1) and significant
      resolution of the disease occurred by day 9. When NPC 15669 (10 mg/kg, i.r.) was
      administered 24 h after acid, MPO accumulation and colonic lesion scores were
      significantly inhibited (days 3-9) and histological examination revealed the
      absence of hemorrhage, epithelial cell regeneration and complete restoration of
      the mucosal architecture. Thus, NPC 15669 prevents colonic damage and promotes
      healing of ulcers, even when administered at the peak of the inflammatory
      response.

PMID- 8273596
TI  - Modulation of T lymphocyte function by the angiogenesis inhibitor AGM-1470.
AB  - The angiogenesis inhibitor AGM-1470 has recently been reported to inhibit
      collagen-induced arthritis in rats. To determine if the anti-arthritic effects of
      AGM-1470 might be due to T cell inhibition, we have studied its effects on T cell
      responses in vitro. Responses of human cells to tetanus toxoid (TT), and those of
      murine splenocytes to staphylococcal enterotoxin (SE), mitogens or a mls
      difference were inhibited by AGM-1470. Responses of human cells to SE, OKT3 and
      PHA were all partially inhibited on day 2 (d2) but not d3, and in fact were
      augmented on d6-8. The amount of IL-2 in SEA cultures was augmented on d4 and d5.
      There were no differences in the expression of CD3, CD4, CD8, CD25, CD45RA,
      CD45RO, LFA-1, VLA-4 or VLA-6 in inhibited cultures, except for slight decreases
      in CD25 and CD45RO in TT cultures. These results indicated that the angiogenesis
      inhibitor AGM-1470 also modulates human and murine lymphocyte function.

PMID- 8273595
TI  - Prevention and suppression of experimental allergic encephalomyelitis by an
      orally active leukocyte recruitment inhibitor, NPC 16570.
AB  - An orally active leukocyte recruitment inhibitor, NPC 16570 (N-[9H-fluoren-9
      ylethoxycarbonyl]-4-aminobenzoic acid), was evaluated in experimental allergic
      encephalomyelitis (EAE) in rats. The mean time of disease onset in control
      animals was 12 +/- 1 days, with peak average clinical scores of 2.5 +/- 0.2,
      accompanied by perivascular infiltration of inflammatory cells into the CNS.
      Daily administration (p.o.) of NPC 16570 reduced the clinical severity (by 70%)
      at 10 and 30 mg/kg, and at 100 mg/kg, no clinical symptoms were detected. When
      NPC 16570 (100 mg/kg) treatment was initiated 7 days after EAE induction, the
      severity (75% inhibition) and duration of the disease were attenuated; 2 out of 6
      animals showed no overt clinical symptoms and perivascular cell infiltration was
      prevented, suggesting potential utility in autoimmune diseases.

PMID- 8273597
TI  - Effects of rolipram and CI-930 on IL-2 mRNA transcription in human Jurkat cells.
AB  - Interleukin-2 (IL-2) is a major mediator of immunologic responses involved in
      many chronic inflammatory diseases. We have investigated the effects of rolipram,
      a PDE-IV inhibitor, and CI-930, a PDE-III inhibitor, on IL-2 gene expression in
      the Jurkat human T cell line. The immunosuppressant cyclosporin A (CsA) was
      included as a positive control. Jurkat cells were stimulated with 1 microgram/ml
      phytohemagglutinin (PHA) and 50 ng/ml phorbol 12-myristate, 13-acetate (PMA) for
      6 h, and mRNA was analyzed using reverse transcription and polymerase chain
      reaction (RT/PCR). IL-2 transcription was greatly inhibited by 1 microM CsA,
      whereas neither 10 microM rolipram nor 10 microM CI-930 had any effect on steady
      state levels of IL-2 mRNA. Therefore, PDE inhibitors do not affect synthesis of
      IL-2 mRNA in this model of activated T cells. This is of interest given that
      these agents inhibit the proliferation of primary T cells. For murine splenocytes
      stimulated by 2.5 micrograms/ml concanavalin A (Con A), rolipram had an IC50 of
      0.09 microM and CI-930 an IC50 of 4.4 microM. These concentrations are below
      those at which IL-2 mRNA synthesis was shown to be unaffected. Therefore, the
      mechanism by which inhibitors of PDE-III and PDE-IV affect T cell proliferation
      is not likely to involve suppression of IL-2 mRNA transcription.

PMID- 8273598
TI  - The effects of several diphosphonates on murine bone marrow proliferation.
AB  - Six diphosphonates were examined for their ability to alter proliferative
      responses of mouse bone marrow cells to recombinant human M-CSF and recombinant
      murine GM-CSF. Risedronate ([2-(3-pyridinyl)-ethylidene] hydroxy bisphosphonic
      acid) added to in vitro cultures at 10 microM, suppressed the response to M-CSF
      by 58%, but had no significant effect on GM-CSF-induced proliferation. Ethane-1
      hydroxy-1,1-bisphosphonic acid (EHDP), dichloromethylene bisphosphonic acid
      (Cl2MBP), 3-amino-1-hydroxy-propylidene-1,1-bisphosphonic acid (APD), (4
      chlorophenyl)-thiomethylene bisphosphonic acid (tiludronate) and
      (cycloheptylamino)-methylene bisphosphonic acid (YM-175) had no significant
      effect. Treatment of mice for 5 or 14 days with 200 mg/kg/day p.o., Cl2MBP or 3
      mg/kg/day p.o. of risedronate failed to inhibit M-CSF- or GM-CSF-induced
      proliferation by recovered bone marrow cells. Addition of Cl2MBP or risedronate
      in vitro to these cells did not reveal any change in sensitivity to CSFs as a
      result of exposure to diphosphonate in vivo.

PMID- 8273599
TI  - PD 141955 and CI-972: 9-deazaguanine analog purine nucleoside phosphorylase
      inhibitors. I. Suppression of the human mixed lymphocyte reaction (MLR).
AB  - Inhibitors of purine nucleoside phosphorylase (PNP) are of interest as potential
      T-cell-selective immunosuppressive agents and for other uses. PD 141955 (9-deaza
      9-(3-thienylmethyl)guanine; 2-amino-3,5-dihydro-7-(3-thienylmethyl)-4H
      pyrrolo[3,2-d]pyrimidin -4-one) is 12- to 100-fold more potent than CI-972 (8
      amino-9-deaza-9-(3-thienylmethyl)guanine; 2,6-diamino-3,5-dihydro-7-(3
      thienylmethyl)-4H-pyrrolo[3,2-d]pyrim idin-4- one) in PNP enzyme inhibition
      assays. In the human MLR, PD 141955 has IC50s of 2.8 and 12.8 microM in the
      presence and absence, respectively, of 15 microM GdR (means from 10 assays),
      while the IC50s of CI-972 tested in parallel are > 30 microM. Concentration
      dependent accumulation of dGTP occurs in PD 141955-treated MLRs under conditions
      in which CI-972 lacks detectable activity. Thus, consistent with its greater PNP
      inhibitory activity in a cell free system, PD 141955 is significantly more potent
      than CI-972 in its ability to suppress the MLR.

PMID- 8273600
TI  - PD 141955 and CI-972: 9-deazaguanine analog purine nucleoside phosphorylase
      inhibitors. II. Effects on nucleoside catabolism in human and rat blood in vitro.
AB  - Patients with deficiency in purine nucleoside phosphorylase (PNP) have elevated
      levels of the PNP substrates inosine, guanosine, and (rarely) 2'-deoxyguanosine
      (GdR) in their plasma and urine. GdR is critical because it serves as a precursor
      of dGTP, which blocks T-cell replication, thus leading to T-cell-selective immune
      dysfunction. We adapted these findings to the study of PNP inhibitors in human
      and rat blood in vitro. Blood was spiked with GdR (2.5 micrograms/ml) and the
      effects of PD 141955 (9-deaza-9-(3-thienylmethyl)guanine; 2-amino-3,5-dihydro-7
      (3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin -4-one) and CI-972 (8-amino-9-deaza
      9-(3-thienylmethyl)guanine; 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H
      pyrrolo[3,2-d]pyrim idin-4- one) on GdR catabolism were determined. GdR was
      metabolized 89 times faster in human blood than in rat blood (half-life = 12.0 +/
      1.4 s in human blood). When PD 141955 (1 microgram/ml) was added to human blood
      before spiking, the GdR half-life increased to > 60 min. In contrast, CI-972 (1
      microgram/ml) extended the GdR half-life to 7.2 +/- 1.7 min. Both PD 141955 and
      CI-972 at 1 microgram/ml significantly retarded GdR catabolism from rat blood.

PMID- 8273601
TI  - Diagnosis of prostatic carcinoma: value of random transrectal sonographically
      guided biopsies.
AB  - OBJECTIVE: We studied the efficacy of random, transrectal sonographically guided
      biopsies in the diagnosis of prostatic carcinoma in a high-risk population.
      SUBJECTS AND METHODS: During a 2-year period, 570 transrectal sonographically
      guided prostatic biopsies were done because of clinical findings suggestive of
      prostatic carcinoma. Biopsies of hypoechoic lesions that were suggestive of
      carcinoma and segmental random biopsies of normal-appearing lobes of the prostate
      were performed. Transrectal sonographic findings were correlated with results of
      pathologic examination of the biopsy specimen and with surgical results, when
      available. RESULTS: Of the 202 patients found to have carcinoma, the carcinoma
      was detected with directed biopsy in 145 patients (72%). One hundred twenty (71%)
      of 169 carcinomas were detected with random biopsy when that procedure was
      performed. Random biopsies were the only method of diagnosing 57 (28%) of the 202
      carcinomas, increasing the yield by 39%. CONCLUSION: Yield of carcinoma on
      transrectal sonographically guided biopsies increases significantly when
      segmental random biopsies are performed. Transrectal sonographically guided
      biopsies should include cores through hypoechoic lesions that are suggestive of
      carcinoma and bilateral segmental random biopsies.

PMID- 8273602
TI  - MR imaging of patients with lateral epicondylitis of the elbow (tennis elbow):
      importance of increased signal of the anconeus muscle.
AB  - OBJECTIVE: The purpose of this study was to determine what changes might be
      detected on MR images of patients with chronic lateral epicondylitis (tennis
      elbow) that could explain why some cases are resistant to therapy. SUBJECTS AND
      METHODS: Seven consecutive patients with chronic lateral epicondylitis were
      included. The diagnosis was based on symptoms and signs characteristic of the
      disease, as determined by each patient's orthopedic surgeon. Three volunteers
      with normal elbows were control subjects. All patients had MR imaging of the
      involved elbow, and control subjects had MR imaging of the nondominant elbow.
      Short tau inversion-recovery (STIR) MR imaging was chosen because of its
      sensitivity to changes in the water content of muscle and its suppression of the
      fat signal. The images were analyzed visually and on an MR workstation to measure
      the signal intensity of the elbow muscles. RESULTS: In all seven patients, MR
      images showed increased signal intensity of the anconeus muscle. This increase in
      signal intensity was not observed in the control subjects, and to our knowledge
      it has not been reported previously. CONCLUSION: Increased signal intensity of
      the anconeus muscle on MR images in patients with chronic lateral epicondylitis
      suggests involvement of the muscle. Increased signal intensity is seen with
      edema, granulation tissue, and inflammation, which may explain the findings in
      this study. Our results are inconclusive as to whether this increased signal
      intensity contributes to the chronicity of patient symptomatology or is
      associated with abnormal elbow motion because of the symptoms.

PMID- 8273603
TI  - Abdominal complications after bone marrow transplantation in children:
      sonographic and CT findings.
AB  - Bone marrow transplantation is increasingly used in children to treat refractory
      malignant neoplasms, immunodeficiency syndromes, and hematopoietic and genetic
      disorders. In preparation for the transplantation, patients receive high doses of
      chemotherapeutic agents and total-body irradiation to destroy residual malignant
      cells or dysfunctional marrow and to prevent rejection of the graft. A variety of
      abdominal and pelvic complications may occur after transplantation because of
      pancytopenia, the direct toxic effects of the preparative regimen, graft-vs-host
      disease, or immunosuppression. This essay illustrates the CT and sonographic
      appearances of these complications.

PMID- 8273604
TI  - Metaphyseal abnormalities in children: pathophysiology and radiologic appearance.
AB  - The most active site of formation of bone in children is the metaphysis. Systemic
      and local diseases are reflected by alterations in the morphology of this region.
      In this pictorial essay, we examine several patterns of metaphyseal abnormalities
      seen on radiologic images and review the associated pathophysiology. Differential
      diagnosis may be aided by considering the pathologic mechanisms responsible for
      the various metaphyseal alterations.

PMID- 8273605
TI  - The corpus callosum: normal fetal development as shown by transvaginal
      sonography.
AB  - OBJECTIVE: Detection of the corpus callosum in the developing fetus on sonograms
      usually is difficult. We determined the normal appearance and development of this
      structure during the second half of pregnancy, as shown on transvaginal
      sonograms. SUBJECTS AND METHODS: One hundred one fetuses were evaluated with
      transvaginal sonography between 18 and 42 weeks' gestation. The length of the
      corpus callosum and the thicknesses of the genu, body, and splenium were
      measured, and growth tables were produced. RESULTS: The corpus callosum was
      detected in 95% of cases and showed gradual enlargement during pregnancy; growth
      was linear, from nearly 17 mm in length at 18 weeks' gestation to 44 mm at term.
      The ratios of the length of the corpus callosum to the anteroposterior diameter
      of the brain remained relatively constant from 20 to 21 weeks' gestation to term.
      CONCLUSION: Transvaginal sonography can be used to visualize and measure the
      corpus callosum in the developing fetus. Data from this study may be useful as a
      reference for normal development of the corpus callosum.

PMID- 8273606
TI  - Hippocampal sclerosis in children with intractable temporal lobe epilepsy:
      detection with MR imaging.
AB  - OBJECTIVE: Hippocampal sclerosis is the most common lesion associated with
      temporal lobe epilepsy. Temporal lobectomy is effective for the control of
      medically refractory seizures in these patients. Before the advent of MR imaging,
      hippocampal sclerosis was rarely diagnosed preoperatively. The purpose of this
      study was to determine the frequency of hippocampal sclerosis in children with
      intractable temporal lobe epilepsy and the accuracy and reliability with which
      hippocampal sclerosis can be diagnosed on the basis of MR findings in children.
      MATERIALS AND METHODS: We reviewed the MR images of 53 children (mean age, 10
      years) with medically refractory temporal lobe epilepsy. The MR images were
      reviewed blindly and independently by two radiologists on two occasions, and were
      classified as showing hippocampal sclerosis, other lesions, or no abnormality.
      Hippocampal sclerosis was diagnosed when evidence of hippocampal atrophy was
      present or hippocampal signal intensity was abnormal without evidence of a mass
      lesion. RESULTS: MR images showed hippocampal sclerosis in 30 children (57%),
      other lesions in 10 (19%) (tumors in eight, cavernous angioma in one, and ectopic
      gray matter in one), and no abnormality in 13 (24%) (intraobserver agreement:
      kappa = 0.77 and 0.84, interobserver agreement: kappa = 0.76). MR lateralization
      was concordant with ictal EEG in 36 (92%) of 39 children. Hippocampal sclerosis
      was bilateral in one child and associated with extrahippocampal lesions in nine.
      Hippocampal sclerosis was detected on MR images of 11 (85%) of 13 children with
      pathologic confirmation of hippocampal sclerosis. Beneficial results were seen in
      26 (90%) of 29 children who had temporal lobectomy. CONCLUSION: Hippocampal
      sclerosis is the most common lesion in children with intractable temporal lobe
      epilepsy, and it can be detected reliably and accurately on MR images. We suspect
      that hippocampal sclerosis is underdiagnosed in children, possibly leading to
      postponement of surgery in children with refractory seizures.

PMID- 8273607
TI  - Progressive multifocal leukoencephalopathy: contrast enhancement on CT scans and
      MR images.

PMID- 8273608
TI  - His own doctor.

PMID- 8273609
TI  - Efficacy of sonographically guided biopsy of thyroid masses and cervical lymph
      nodes.
AB  - OBJECTIVE: We performed a prospective study in 96 patients to determine accuracy
      of sonographically guided fine-needle aspiration biopsy of thyroid masses and
      cervical lymph nodes. MATERIALS AND METHODS: Real-time sonography was used to
      guide biopsy of 112 cervical masses in 96 patients (71 patients with impalpable
      masses, 16 with failed unguided attempts, patient's or physician's preference in
      nine). The diameters of all masses were less than 3 cm, with a mean of 1.5 cm and
      a median of 1.5 cm. Twenty-nine masses measured 1 cm or less in diameter, 60
      masses between 1.1 and 2.0 cm, and 23 masses between 2.1 and 3.0 cm. Cervical
      masses that were sampled by biopsy included 75 thyroid masses and 37 lymph nodes.
      RESULTS: Diagnostic specimens were obtained in 102 (91%) of 112 masses sampled.
      Sixty-eight (91%) of 75 biopsies of thyroid tissue and 34 (92%) of 37 biopsies of
      lymph nodes were diagnostic. Nondiagnostic thyroid biopsies included four of
      complex cysts and three of solid nodules. Sonographic follow-up (1 year) revealed
      no change or decrease in size of those seven lesions. Sixty of 68 diagnostic
      thyroid biopsies showed benign processes: 42 macrofollicular adenomas, six
      colloid adenomas, five microfollicular adenomas, four probable cases of
      thyroiditis, and three hemorrhagic cysts. The remaining eight diagnostic thyroid
      biopsies showed malignant processes: seven papillary carcinomas and one
      metastatic small-cell carcinoma. Of 34 diagnostic biopsies of lymph nodes, 26
      showed malignant processes and eight showed benign processes. Surgery in the
      three patients with nondiagnostic biopsies of lymph nodes revealed two recurrent
      medullary cancers and one benign node. CONCLUSION: Sonographically guided fine
      needle aspiration biopsy of neck masses has a high sensitivity (91%) and should
      be routinely used to evaluate indeterminate masses in the neck.

PMID- 8273610
TI  - Percutaneous neurolysis of the celiac plexus via the anterior approach with
      sonographic guidance.
AB  - OBJECTIVE: The purpose of this study was to evaluate the usefulness of
      sonographically guided percutaneous neurolysis of the celiac plexus in patients
      with abdominal tumors or chronic pancreatitis in whom systemic analgesics were
      ineffective. SUBJECTS AND METHODS: Neurolysis of the celiac plexus was performed
      in 38 patients, 34 with neoplastic disease and four with chronic pancreatitis.
      Under sonographic guidance, a 22-gauge needle was advanced by the anterior route
      to the area above the celiac plexus, and 30-40 ml of 50% alcohol was injected.
      Pain relief was assessed 1 week, 6 months, and 1 year after the procedure.
      Patients subjectively rated the pain after treatment as totally relieved,
      partially relieved, or unchanged. RESULTS: At 1 week and at 6 months after
      treatment, pain was totally relieved in 61% of patients, partially relieved in
      31%, and unchanged in 8%. After 1 year, pain was totally relieved in 39%,
      partially relieved in 52%, and unchanged in 9%. The complications observed were
      five cases of mild diarrhea and one case of retroperitoneal pain, which subsided
      with conservative treatment. CONCLUSION: The anterior, sonographically guided
      approach appears to be as successful as other percutaneous techniques for
      neurolysis of the celiac plexus.

PMID- 8273611
TI  - The fourth declension.

PMID- 8273612
TI  - Percutaneous ethanol injection of hepatic tumors: single-session therapy with
      general anesthesia.
AB  - OBJECTIVE: We studied the feasibility and the effectiveness of percutaneous
      ethanol injection, performed with general anesthesia in a single session, for
      treating malignant hepatic lesions. SUBJECTS AND METHODS: We treated 30 patients
      with sonographically guided percutaneous injection of ethanol. Twenty had
      hepatocellular carcinoma and cirrhosis, and 10 had hepatic metastases,
      principally from colon cancer. The mean volume of ethanol injected was 57 ml
      (range, 6-165 ml). RESULTS: CT showed complete necrosis (up to 8.2 cm) in seven
      of 10 patients with encapsulated hepatocellular carcinoma and about 90% necrosis
      in the remaining three patients. In four of these patients, the alpha-fetoprotein
      level fell from more than 200 ng/ml to less than 20 ng/ml during treatment. In 10
      patients with infiltrating hepatocellular carcinoma, about 70-90% necrosis was
      achieved; in six of these patients, the alpha-fetoprotein level, which had been
      more than 200 ng/ml, decreased during treatment. In the 10 patients with
      metastases, more than 50% necrosis was always achieved. Levels of
      carcinoembryonic antigen decreased after treatment in all patients. In three
      patients who had cirrhosis with superficial hepatocellular carcinoma, peritoneal
      hemorrhage occurred but did not require transfusion. CONCLUSION: Our results show
      that percutaneous injection of ethanol in a single session with general
      anesthesia is feasible and effective and has several advantages over multisession
      therapy. These include shorter treatment time and the ability to treat larger and
      more numerous lesions.

PMID- 8273613
TI  - Percutaneous injection of ethanol in a patient with a solitary hepatocellular
      carcinoma.

PMID- 8273614
TI  - Lightweight aprons for protection against scattered radiation during fluoroscopy.

PMID- 8273615
TI  - Extraosseous multiple myeloma: imaging features.
AB  - Multiple myeloma is a disseminated malignant neoplasm usually derived from a
      single clone of plasma cells. Patients with myeloma have diverse signs such as
      anemia, hypercalcemia, uremia, pathologic fractures, and recurrent infections.
      Extraosseous manifestations are found in less than 5% of patients with multiple
      myeloma. They can arise in any tissue, and their presence has been associated
      with more aggressive disease. The purpose of this essay is to illustrate the
      imaging findings of extraosseous myeloma and heighten awareness of this unusual
      manifestation of multiple myeloma.

PMID- 8273616
TI  - Adverse reactions to contrast media: factors that determine the cost of
      treatment.
AB  - OBJECTIVE: The purpose of this study was to determine the cost of treating
      adverse reactions to contrast material that occur in patients with different
      clinical characteristics, the characteristics of patients who have adverse
      reactions that are expensive (> $500) to treat, and the types of adverse
      reactions that are expensive to treat. The cost of patient care associated with
      treating complications of medical procedures is an important consideration when
      evaluating the cost effectiveness of medical practices. Information about the
      cost of treating complications can be useful in guiding the development and
      application of new and safer strategies for patient care. SUBJECTS AND METHODS:
      We performed an economic analysis of data collected in a clinical trial comparing
      the safety of low- vs high-osmolality radiologic contrast media in 1004 patients
      who underwent either cardiac angiography or contrast-enhanced body CT; 193 (19%)
      of these patients had at least one adverse reaction. By means of bivariate and
      multivariate analyses, we examined the association between the cost of treating
      adverse reactions to contrast material and the baseline characteristics (age,
      sex, race, radiologic procedure, contrast medium, preexisting disease) of
      patients and clinical features (type and/or number of different types) of these
      reactions. RESULTS: The mean cost per patient to the hospital of treating adverse
      reactions to contrast material among the 193 patients who sustained a reaction
      was $459 (range, $0-39,057). The mean cost varied with the type and number of
      reactions, ranging from $32 (+/- $13) for treatment of increased systolic blood
      pressure to $15,360 (+/- $7994) for treatment of thromboembolism. Bivariate and
      multivariate analyses showed the variables associated with higher cost of
      treating reactions: cardiac angiography vs body CT (mean cost, $476 vs $198), a
      history vs no history of unstable angina (mean cost, $930 vs $208), a history vs
      no history of renal insufficiency (mean cost, $2064 vs $152), two adverse
      reactions (mean cost, $221) or three or more reactions (mean cost, $3585) vs one
      reaction (mean cost, $161), and a thromboembolic reaction (mean cost, $15,360).
      These variables explained 38% of the variation in the costs of treating adverse
      reactions to contrast material (p < .0001). CONCLUSION: Costs of treating adverse
      reactions to contrast material vary, both overall and by type and extent of
      reaction. Cardiac angiography, a history of unstable angina or renal
      insufficiency, multiple (two or more types of) adverse reactions, and
      thromboembolism are major factors that contribute to the cost of such treatment.
      Future strategies of patient care should be directed at reducing the risk of
      adverse reactions to contrast material for patients with these characteristics
      and at reducing the cost of treating these particularly expensive adverse
      reactions.

PMID- 8273617
TI  - Using a personal computer to create anatomic drawings for publication.
AB  - A chronic need exists for anatomic drawings that are suitable for publication.
      The best drawings of this type are the result of close collaboration between a
      trained medical illustrator and the author commissioning the artwork. However,
      high-quality drawings usually command premium prices and are not within
      everyone's budget. Similarly, services that can provide such illustrations are
      not available in all areas. This paper describes several methods of producing
      high-quality anatomic drawings with a personal computer. These drawings can be
      produced from the digital images obtained on one's local CT or MR scanners, or
      from digitized slides and photographs. Other images can be scanned from various
      sources of anatomic line art that are in the public domain. A final source of
      anatomic drawings is commercially available medical clip art. The drawings
      created from any of these sources can be modified to suit one's needs and can
      provide very satisfactory results.

PMID- 8273618
TI  - Quality assurance: a system that integrates a digital dictation system with a
      computer data base.
AB  - One of the most challenging responsibilities for radiologists is assessment of
      the quality of care that they provide. Some parameters of quality, such as false
      negative rate, are almost impossible to calculate with absolute precision. The
      issue is also complicated when one tries to determine exactly what constitutes a
      "discordant" interpretation. However, even when a radiologist discovers that a
      radiographic finding was missed, or that an inappropriate examination was done,
      the steps necessary to perform an analysis of the problem can be very disruptive
      to one's clinical focus at the moment. This suggests that a major obstacle to
      participation in quality assurance by radiologists is the lack of an adequate
      infrastructure. We have integrated our digital dictation system with a personal
      computer data base for tracking cases appropriate for quality assurance, thus
      allowing radiologists to log any examination from any dictation station in our
      department with minimal interruption to their clinical activities. Quality
      assurance and peer review are facilitated by using a personal computer for
      otherwise tedious aspects of information management. Radiology departments that
      have a convenient, department-wide method for entering cases--such as a digital
      dictation system--are ideal for this technique.

PMID- 8273619
TI  - Henry P. Bowditch's forgotten contributions to radiology.

PMID- 8273620
TI  - More on pitfalls in medical writing.

PMID- 8273621
TI  - Clot in the pulmonary artery after pneumonectomy.

PMID- 8273622
TI  - Position-dependent mediastinal mass: aneurysm of the superior vena cava.

PMID- 8273623
TI  - Primary chemodectoma of the lung.

PMID- 8273624
TI  - Relationship of breast compressibility to mammographic pattern of parenchymal
      density.

PMID- 8273625
TI  - Mammographic appearance of tubular carcinoma.

PMID- 8273626
TI  - Subspecialization and women's imaging.

PMID- 8273627
TI  - Historic perspective on the use and misuse of radiologic information.

PMID- 8273628
TI  - Mammography and malpractice litigation: current status, lessons, and admonitions.

PMID- 8273629
TI  - Cardiopulmonary complications of pregnancy: radiographic findings.
AB  - Physiologic changes during pregnancy affect nearly every organ system. In the
      thorax, the diaphragm elevates as much as 4 cm because of displacement of the
      abdominal organs by the gravid uterus, resulting in lower lung volumes. Maternal
      blood volume and cardiac output increase approximately 45% by mid-pregnancy.
      Cardiac output can increase as much as 80% during vaginal delivery and up to 50%
      with cesarean section. These changes result in pulmonary vascular engorgement,
      progressive left ventricular dilatation, and mild hypertrophy (Fig. 1). Pregnant
      patients are also prone to a number of pulmonary insults, including infection,
      aspiration, and neoplastic disease. These abnormalities have several radiographic
      patterns: cardiogenic and noncardiogenic pulmonary edema, focal pulmonary
      abnormalities, and extraalveolar air. Radiologists must recognize not only the
      normal chest radiographic appearance in these patients but also the thoracic
      complications associated with pregnancy.

PMID- 8273630
TI  - Cardioverter-defibrillator systems implanted without thoracotomy: radiographic
      findings.
AB  - Ventricular arrhythmias are the primary cause of sudden death from heart disease
      in the United States. In the past decade, management of these arrhythmias has
      been revolutionized by the development of implantable cardioverter-defibrillators
      (ICDs). Earlier devices required thoracotomy for implantation (Fig. 1).
      Complications associated with the earlier devices include pneumothorax, pleural
      effusion, mediastinal infection, and, notably, crinkling of the patch and
      migration. The morbidity of median sternotomy has led to the development of ICDs
      that can be implanted without thoracotomy. We illustrate the normal radiographic
      appearance and complications of two recently developed ICD lead systems.

PMID- 8273631
TI  - Anastomotic stenosis of the left pulmonary artery after lung transplantation:
      treatment by percutaneous placement of an endoprosthesis.

PMID- 8273632
TI  - Aneurysm of a saphenous vein graft manifested as a mediastinal mass on chest
      radiographs.

PMID- 8273633
TI  - Mammographic surveillance of breast cancer patients: should the mastectomy site
      be imaged?
AB  - OBJECTIVE: This study evaluated the usefulness of routine mammography of the
      mastectomy site in women who have been treated for breast carcinoma. MATERIALS
      AND METHODS: From a retrospective review of medical records and mammographic
      examinations of 827 patients who had mastectomies, the following information was
      obtained: demographic data, type of breast reconstruction (if any), length of
      follow-up after mastectomy, evidence of local recurrence, and results of physical
      examination of the breast and mammography immediately before diagnosis of local
      recurrence. RESULTS: Local recurrences of breast cancer were seen in 39 (4.5%) of
      the 859 breasts in the study group. All patients had a physical examination of
      the breast and mammography within 3 months of the diagnosis of recurrent breast
      carcinoma. Mammography of the mastectomy site did not show any recurrences that
      were not suspected on the basis of physical examination. For two of 20 patients,
      spot-compression views of palpable abnormalities showed thickening of the
      surgical scar. In four patients with pain in the chest wall, no abnormalities
      were found on physical examination or mammograms, but bone scintigrams showed
      metastasis to the ribs. CONCLUSION: Our results indicate that mammographic
      imaging of the mastectomy site does not increase the detection of locally
      recurrent breast cancer.

PMID- 8273634
TI  - Invasive lobular carcinoma of the breast: mammographic findings and extent of
      disease at diagnosis in 184 patients.
AB  - OBJECTIVE: Invasive lobular carcinoma of the breast is a distinct malignant
      neoplasm consisting of small cells that tend to infiltrate in thin strands that
      are often only one cell in width. The objectives of this study were to determine
      if these tumors are more frequently overlooked on mammograms than are other types
      of invasive carcinoma and to evaluate the specific mammographic and pathologic
      findings of this disease at the time of diagnosis. MATERIALS AND METHODS: From
      1983 through 1991, invasive, purely lobular carcinoma of the breast was diagnosed
      in 184 women who had screen-film mammography and biopsy at our institution. We
      examined the initial mammographic reports to determine the principal abnormal
      mammographic findings that supported or prompted biopsy and to distinguish
      abnormalities that were overlooked in breasts with false-negative mammographic
      findings. All mammograms were retrospectively examined for benign or suspicious
      microcalcification in the vicinity of the neoplasm and for breast parenchymal
      patterns. Surgical pathology reports were also reviewed. RESULTS: The rate of
      false-negative findings on initial interpretations of mammograms was 19%. Forty
      six percent of the mammograms with false-negative initial interpretation showed
      no evidence of malignant tumor in retrospect. Ten percent of the neoplasms showed
      suspicious calcification on mammograms, and 1% of patients had biopsy primarily
      because of worrisome calcification. Invasive lobular carcinoma tends to produce
      masses that are of relatively low radiographic opacity, similar to normal
      fibroglandular breast tissue. Forty-four percent of patients had metastases to
      axillary lymph nodes at the time of diagnosis. One patient had bilateral invasive
      lobular carcinoma. CONCLUSION: Our results show that the false-negative rate for
      the diagnosis of invasive lobular carcinoma is higher than that for other
      invasive cancers. The reasons for this difference appear to be the low rate of
      suspicious calcification found with invasive lobular carcinoma and its tendency
      to be of low opacity. We also found a lower rate of bilateral invasive lobular
      carcinoma than has been generally reported. Metastases to lymph nodes were common
      at the time of diagnosis.

PMID- 8273635
TI  - Milk fistula: a complication after core breast biopsy.

PMID- 8273636
TI  - Multicentric granulocytic sarcoma (chloroma) of the breast: mammographic
      findings.

PMID- 8273637
TI  - Antispasmodic drugs to reduce discomfort and colonic spasm during barium enemas:
      comparison of oral hyoscyamine, i.v. glucagon, and no drug.
AB  - OBJECTIVE: Parenterally administered glucagon is currently the agent of choice
      for reducing abdominal discomfort and colonic spasm during a barium enema.
      Because glucagon is expensive and frequently causes nausea, we evaluated the use
      of oral hyoscyamine sulfate as an alternate agent and compared it with IV
      glucagon and no medication. SUBJECTS AND METHODS: A total of 349 adult patients
      undergoing barium enema examinations were randomly assigned in a prospective
      fashion to one of four groups: (1) no medication (87 patients); (2) 1 mg of IV
      glucagon (88 patients); (3) 0.125 mg of oral hyoscyamine sulfate (87 patients);
      and (4) 0.25 mg of oral hyoscyamine sulfate (87 patients). The degree of
      distension of the colon on radiographs obtained after fluoroscopy, the amount of
      abdominal distress after the procedure, and the number of side effects (nausea,
      palpitations, blurred vision, dry mouth) were analyzed. To evaluate the amount of
      abdominal discomfort more completely, we asked the last 248 patients to estimate
      the level of severity of the discomfort (none, mild, moderate, or severe).
      RESULTS: We found no difference in the degree of distension of the colon in the
      four groups (p = .63). Most patients (79%) had some degree of abdominal
      discomfort. Fewer patients in the group who received no medication (10%) had no
      or mild pain compared with those given glucagon (15%, p < .05), 0.125 mg of
      hyoscyamine (14%, p < .05), or 0.25 mg of hyoscyamine (12%, p = .15). Less nausea
      occurred in the group that received 0.125 mg of hyoscyamine than in the other
      groups (p < .03). No patients in any of the groups had allergic or severe side
      effects. CONCLUSION: When compared with IV glucagon, oral hyoscyamine had fewer
      side effects, but the degree of colonic distension or abdominal distress was not
      significantly different. In addition, hyoscyamine is considerably less expensive
      than glucagon and can be given orally. Patients who received medications had less
      discomfort than those who did not. However, the degree of distension was not
      different.

PMID- 8273638
TI  - Contrast examination of the small bowel in patients with small-bowel transplants:
      findings in 16 patients.
AB  - OBJECTIVE: The purpose of this study was to describe the findings on contrast
      examinations of the gastrointestinal tract in patients with small-intestinal
      transplants. SUBJECTS AND METHODS: Sixteen consecutive adult transplant
      recipients received a total of 17 allografts: eight isolated small-bowel, six
      small-bowel and liver, and three multivisceral (stomach, duodenum, pancreas,
      small-bowel, liver). Grafts included the entire mesenteric small bowel.
      Gastrointestinal contrast studies were done in asymptomatic patients according to
      protocol and in patients having clinical indications for examination. Median time
      from transplantation to examination was 78 days (range, 5-768 days). Seventy-five
      gastrointestinal contrast examinations were performed: 53 upper gastrointestinal
      and small-intestinal series, 12 upper gastrointestinal series, eight
      enteroclyses, and two water-soluble contrast enemas. Radiographs were analyzed
      for postsurgical anatomy, integrity of anastomoses, allograft radiologic
      appearance, small-bowel transit time, and rate of gastric emptying. RESULTS:
      Usual postsurgical anatomy included native-to-donor duodenojejunal,
      jejunojejunal, and gastrogastric anastomoses and donor-to-native ileocolonic and
      ileoileal anastomoses. No anastomotic complications were found. Leaks at native
      duodenal and colonic stumps resulted in a duodenocutaneous fistula and an
      abscess, respectively. Moderate to marked thickening of mucosal folds consistent
      with edema was present in nine allografts (53%) and 11 (17%) of 66 upper
      gastrointestinal and small-intestinal examinations, primarily in the early
      postoperative period. Chronic loss of allograft mucosal folds developed in four
      grafts in three patients; pathologic diagnoses included acute and chronic
      rejection and enteric infection; a jejunocutaneous fistula developed in one such
      patient. Transit times of barium through the small intestine ranged from 0.2 to
      17.8 hr (median, 2 hr). Self-limited delayed gastric emptying was present in 14
      patients (88%) and 32 (60%) of 54 upper gastrointestinal and small-intestinal
      examinations. CONCLUSION: Gastrointestinal contrast examinations in recipients of
      small-bowel transplants are useful for assessing graft anatomy, enteric
      anastomoses, and gastrointestinal motor function. Most intestinal grafts showed
      normal caliber and mucosal pattern and exhibited active peristalsis. Abnormal
      findings included self-limited postoperative edema of graft mucosal folds,
      chronic loss of the mucosal folds due to rejection and/or enteric infection,
      delayed gastric emptying that improved with time, leaks from native duodenal and
      colon stumps, and a jejunocutaneous fistula in a failing graft. Small-intestinal
      transit times were similar to those observed in patients not receiving
      transplants, although there was wide variation.

PMID- 8273639
TI  - Local recurrence after surgery for gastric carcinoma: CT findings.
AB  - Local recurrence of gastric carcinoma after surgery is defined as histologic
      evidence of a tumor in the surrounding tissues of the resected stomach. Compared
      with the large number of articles describing tumor recurrence after colectomy for
      colonic carcinoma, few reports have been published on the CT findings after
      gastrectomy. We illustrate the CT features of local tumor recurrence after
      gastrectomy in 36 patients in whom recurrence was confirmed pathologically or by
      definitive findings on CT scans.

PMID- 8273640
TI  - Myxomatous degeneration of renal capsular leiomyoma.

PMID- 8273641
TI  - CT of hypervascular hepatic tumors: are unenhanced scans necessary for diagnosis?
AB  - OBJECTIVE: In most institutions, a combination of unenhanced and contrast
      enhanced CT is used to screen patients for suspected hypervascular hepatic
      neoplasms. Elimination of the unenhanced examination could save time and expense
      and reduce the patient's exposure to radiation. We compared unenhanced and
      incremental bolus dynamic contrast-enhanced CT for detection of hypervascular
      hepatic neoplasms and evaluated the need for preliminary unenhanced hepatic CT.
      SUBJECTS AND METHODS: We prospectively examined 101 consecutive patients with
      hypervascular primary hepatic malignant tumors or suspected hypervascular
      metastases. Primary hepatic neoplasms included hepatocellular carcinoma (seven),
      sarcoma (two), and hemangioendothelioma (one); extrahepatic primary tumors
      included breast (37) and renal cell (24) carcinoma, melanoma (15), carcinoid
      (nine), and endocrine and other tumors (six). All patients had both unenhanced
      and bolus dynamic contrast-enhanced CT with 5-mm collimated sections at 8-mm
      intervals. For contrast-enhanced CT, 150-180 ml of IV contrast material, a
      mechanical power injector, and a scanning protocol that allowed completion of
      liver imaging within 2 min were used. Both unenhanced and contrast-enhanced CT
      scans were compared for detection and conspicuousness of hepatic lesions.
      RESULTS: Hepatic lesions were found in 34 patients. In 21 patients, all hepatic
      lesions seen on unenhanced scans also were apparent on contrast-enhanced scans.
      However, in 12 (57%) of 21 patients, lesions were more conspicuous and better
      defined on contrast-enhanced scans. The absolute number of lesions detected with
      each method of scanning differed in 12 patients. In four patients, the contrast
      enhanced scan showed more lesions; in five patients, the unenhanced scan showed
      more lesions; and in three patients, administration of contrast material obscured
      some lesions shown on unenhanced scans and made others more conspicuous. If only
      a contrast-enhanced CT scan had been obtained, the presence of malignant hepatic
      neoplasm would have been missed in only one case (a patient with a single 2.8-cm
      metastasis from renal cell carcinoma). CONCLUSION: Bolus dynamic contrast
      enhanced CT alone correctly showed the presence or absence of primary or
      metastatic hypervascular hepatic tumors in 100 of 101 cases. If the goal of CT
      examination is detection of hypervascular hepatic lesions, use of contrast
      enhanced CT alone may be adequate and the addition of unenhanced scans is not
      cost-effective.

PMID- 8273642
TI  - Significant disease of the celiac and superior mesenteric arteries in
      asymptomatic patients: predictive value of Doppler sonography.
AB  - OBJECTIVE: The purpose of this study was to assess the frequency of significant
      disease (i.e., occlusion or stenosis > 70%) of the celiac and superior mesenteric
      arteries in asymptomatic patients. SUBJECTS AND METHODS: Using duplex sonographic
      criteria obtained from previous angiographic-duplex Doppler correlation studies,
      we assessed the frequency of significant disease in the celiac and superior
      mesenteric arteries in 184 patients who had no signs or symptoms of mesenteric
      ischemia. RESULTS: For patients less than 65 years old, the frequency of
      significant disease was 3%, and it was isolated to the celiac artery. Significant
      disease was found in 18% of patients more than 65 years old (in 11%, isolated to
      one vessel; in 7%, disease of both vessels). Single-vessel disease was more
      common in the celiac artery (81%) than in the superior mesenteric artery (19%).
      CONCLUSION: These results indicate that the finding of significant abnormality of
      the celiac and superior mesenteric arteries on Doppler sonograms does not
      necessarily indicate mesenteric ischemia.

PMID- 8273643
TI  - Imaging of the portal venous system in patients with cirrhosis: MR angiography vs
      duplex Doppler sonography.
AB  - OBJECTIVE: To determine the relative performances of MR angiography and duplex
      Doppler sonography in the evaluation of the portal venous system in patients with
      portal hypertension, we compared two-dimensional time-of-flight MR angiography
      and duplex Doppler sonography in 60 sequential patients with cirrhosis. All 60
      subsequently underwent liver transplantation. SUBJECTS AND METHODS: MR imaging
      and duplex Doppler sonography were performed on the same day, and in all patients
      the imaging findings were validated at surgical exploration. Five transplantation
      candidates had surgical portosystemic shunts in situ at the time of imaging. MR
      images were acquired during breath-holding, and flow in the portal vein was
      evaluated with presaturation bolus-tracking MR imaging. Sonography included color
      Doppler and pulsed gated Doppler images of the portal vein. MR angiograms and
      sonograms were analyzed independently and prospectively for patency of the portal
      vein, patency of surgical shunts, and grade and distribution of portosystemic
      collateral vessels. Scores on both imaging techniques were compared by using
      regression analysis. RESULTS: MR angiograms showed all five cases of portal vein
      occlusion and all 55 cases of patent portal veins. Sonograms showed three of five
      cases of portal vein occlusion and 52 of 55 cases of patent portal veins. The
      techniques concurred in assessing flow direction in 54 (90%) of 60 patients, and
      both procedures enabled detection of occlusive portal vein thrombus in one
      patient. We found a significant correlation (p < .001) between the grades of
      gastric varices detected with MR angiography and surgery but no significant
      correlation between the grades seen on sonography and found at surgery. Shunt
      patency in four of five patients and shunt occlusion in one were correctly
      assessed on MR angiograms, whereas three of these shunts were not visible on
      sonograms. CONCLUSION: Our results show that MR angiography is more reliable than
      duplex Doppler sonography for evaluating the portal venous system in patients
      with portal hypertension caused by cirrhosis.

PMID- 8273644
TI  - Measurement of normal renal artery blood flow: cine phase-contrast MR imaging vs
      clearance of p-aminohippurate.
AB  - OBJECTIVE: The purpose of this study was to compare cine phase-contrast MR
      imaging with renal clearance of p-aminohippurate for measuring normal renal blood
      flow. A reliable technique for evaluation of renal hemodynamics would be useful
      for studying renal vascular diseases and the effects of treatment. Measurements
      of renal blood flow based on renal clearance of p-aminohippurate are limited in
      that the kidneys are not studied separately, temporal resolution is poor, and
      normal renal function is required. SUBJECTS AND METHODS: Bilateral oblique
      sagittal cine phase-contrast MR images were obtained simultaneously in 10 healthy
      adult volunteers, with the imaging planes oriented perpendicular to the left and
      right renal arteries in order to measure through-plane flow. Velocity encoding
      was 150 cm/sec (seven of 10 volunteers) and 100 cm/sec (eight of 10 volunteers).
      Axial cine phase-contrast images of the abdominal aorta above and below the
      origins of the renal arteries were obtained in six volunteers. In these cases,
      renal blood flow was determined by measuring the difference between suprarenal
      and infrarenal aortic flow. For all volunteers, renal clearance of p
      aminohippurate was determined immediately after MR measurements. RESULTS: Renal
      blood flow measurements determined by using cine phase-contrast MR imaging were
      in close agreement with those determined by using clearance of p-aminohippurate.
      At a velocity encoding of 150 cm/sec, the mean difference was 69 ml/min (95%
      confidence interval, -31 to 169 ml/min). At a velocity encoding of 100 cm/sec,
      the mean difference was 39 ml/min (95% confidence interval, -100 to 177 ml/min).
      Aortic flow measurements using cine phase-contrast MR imaging appeared to be less
      reliable for determining renal blood flow than measurements in the individual
      renal arteries, with a mean difference of -75 ml/min (95% confidence interval, 
      381 to 231 ml/min) compared with renal blood flow determined by using clearance
      of p-aminohippurate. CONCLUSION: We conclude that cine phase-contrast MR imaging
      is a promising technique for noninvasive measurement of renal blood flow.
      Measurements agreed closely with those obtained by using clearance of p
      aminohippurate. In addition, the MR technique is faster, can be used to measure
      unilateral or bilateral renal blood flow, and does not depend on renal function.

PMID- 8273645
TI  - Eugene W. Caldwell Lecture. Clinical efficacy of diagnostic imaging: love it or
      leave it.
AB  - The traditional goal of radiology has been to provide images of the highest
      technical quality that permit the most accurate diagnoses possible. From a more
      global perspective, diagnostic radiology is part of a larger system that has as
      its goal effective and efficient treatment of patients. A six-tiered hierarchical
      model of efficacy that includes this more global view is presented. This model is
      intended to improve understanding of the continuum that efficacy is and to
      conceptually relate efficacy to technology assessment and outcome research.
      Better understanding of efficacy/technology assessment and outcome research
      fostered by the model should encourage radiologists to participate actively in
      federally supported research in these areas. Those radiologists who do so will
      come to understand better how radiology can help patients and society as a whole.
      Use of the model's concepts should also aid radiologists in becoming more
      effective consultants to their clinical colleagues about optimal use of high
      technology imaging from the perspectives of clinical efficacy, patient outcome,
      and societal efficacy.

PMID- 8273646
TI  - Parosteal lipoma: MR imaging characteristics.
AB  - OBJECTIVE: The purpose of this study was to determine the characteristics of
      parosteal lipomas on MR imaging. MATERIALS AND METHODS: We retrospectively
      reviewed the images and medical records of eight patients with surgically and
      pathologically confirmed parosteal lipomas. Radiologic studies performed included
      conventional radiography and MR imaging (n = 8), CT (n = 7), conventional
      tomography (n = 2), and scintigraphy (n = 5). RESULTS: Osseous reaction was
      present in all cases, manifesting as either mild cortical thickening best seen on
      magnification radiographs or larger osseous excrescences seen on all radiologic
      images. These osseous reactions were surrounded by the lipomatous component of
      the neoplasm and created a firm attachment of the neoplasm to the underlying
      bone. The lipomatous component showed typical features of adipose tissue on all
      images and was usually seen on radiographs (n = 7). However, CT or MR imaging was
      needed to determine the anatomic location and relationship to surrounding
      structures before surgery. MR imaging was considered superior to CT for
      preoperative assessment, primarily because of its multiplanar imaging capability.
      In addition, cartilage and fibrous tissue (n = 3) were identified adjacent to
      larger osseous excrescences. Associated muscle atrophy in three cases was caused
      by nerve impingement. These manifestations of parosteal lipoma were also better
      assessed with MR images because of improved contrast resolution. The distribution
      of muscle atrophy could be used to determine the site of nerve involvement
      preoperatively. CONCLUSION: We conclude that MR imaging is the most useful
      adjunct to conventional radiography in the presurgical evaluation of parosteal
      lipomas because of its multiplanar imaging capabilities and improved contrast
      resolution for detecting muscle atrophy and site of nerve involvement when
      present. These factors are important for preoperative assessment to help guide
      surgical intervention.

PMID- 8273647
TI  - Fluid in normal and abnormal ankle joints: amount and distribution as seen on MR
      images.
AB  - OBJECTIVE: The appearance of fluid in tendon sheaths of the ankle joint and in
      ankle articulations seems to vary. To determine the degree of this variability
      and to see if fluid occurs in normal ankles, we evaluated the presence, amount,
      and distribution of joint fluid as seen on MR images of normal and abnormal
      ankles. MATERIALS AND METHODS: The study included 40 normal ankles of volunteers,
      15 ankles of patients with disorders of the posterior tibial tendon, 73 ankles of
      patients with disorders not involving tendons studied (occult fractures,
      osteochondritis dissecans, and Achilles tendon disorders), and 46 asymptomatic
      ankles of patients with disorders of the opposite ankle. We analyzed the MR
      images of these ankles to determine the volume of fluid in the ankle and subtalar
      joints. We also analyzed the relative volumes of fluid in tendon sheaths. We then
      compared the results in patients who had symptoms with those in asymptomatic
      subjects and developed an algorithm of fluid interrelationships. RESULTS: Most
      patients had fluid in the ankle (77%) and subtalar joints (72%). Fluid was common
      around all tendons except the extensor tendons. Large amounts of fluid were
      particularly common around the flexor hallucis longus tendon (14%). No
      statistically significant difference in the prevalence or relative volumes of
      fluid in the subtalar or ankle joints or tendon sheaths was found between normal
      and abnormal ankles. A close relationship was found between volumes of fluid
      between tendons, usually those in close proximity to each other. We found no
      correlation between fluid in the subtalar and ankle joints. CONCLUSION: Our
      results show that fluid in the articulations and tendon sheaths of the ankle is
      common in asymptomatic patients, and the amounts of fluid are not significantly
      different from the amounts in patients with symptoms. There also appear to be
      complex interrelationships between fluid seen in the joint and in tendon sheaths.

PMID- 8273648
TI  - MR diagnosis of tears of anterior cruciate ligament of the knee: importance of
      ancillary findings.
AB  - OBJECTIVE: Detection of tears of the anterior cruciate ligament with MR is
      usually based on the appearance of the ligament. However, other MR findings may
      be useful to establish the diagnosis. We assessed the utility of these ancillary
      MR findings for detecting tears and for differentiating partial from complete
      tears of the anterior cruciate ligament. MATERIALS AND METHODS: MR images of 68
      patients who had arthroscopic correlation were retrospectively reviewed by two
      radiologists who did not know the arthroscopic findings. The reviewers noted the
      presence and location of bone bruises (nonlinear low signal in the bone marrow on
      T1-weighted images), assessed posterior displacement of the posterior horn of the
      lateral meniscus, and measured the posterior cruciate ligament angle. At
      arthroscopy, 39 patients had tears of the anterior cruciate ligament (24
      complete, 15 partial) and 29 had intact anterior cruciate ligaments. RESULTS: The
      presence of bone bruising in the posterolateral tibial plateau had sensitivities
      of 50% and 46%, with corresponding specificities of 97% and 97% for the two
      reviewers. Posterior displacement of the posterior horn of the lateral meniscus
      had a sensitivity of 56% for both reviewers, with 100% and 97% specificities. An
      angle of the posterior cruciate ligament less than 105 degrees had sensitivities
      of 72% and 74%, with corresponding specificities of 79% and 86%. The prevalence
      of these findings was similar in patients with partial tears and those with
      complete tears. CONCLUSION: Ancillary MR imaging findings may be helpful for
      diagnosing tears of the anterior cruciate ligament when diagnosis based on the MR
      appearance of the ligament is equivocal. Ancillary findings cannot be used to
      differentiate patients with partial tears from those with complete tears. The
      presence of bone bruising in the posterior aspect of the tibial plateau and
      posterior displacement of the posterior horn of the lateral meniscus are highly
      specific for a torn anterior cruciate ligament; therefore, the presence of either
      of these findings should be considered strong evidence of a tear of the anterior
      cruciate ligament.

PMID- 8273649
TI  - Radiographic diagnosis of acromioclavicular joint separation without weight
      bearing: importance of internal rotation of the arm.

PMID- 8273650
TI  - Abnormality of cerebellar vermian lobules VI and VII in patients with infantile
      autism: identification of hypoplastic and hyperplastic subgroups with MR imaging.
AB  - OBJECTIVE: Infantile autism is a neurobehavioral disorder that is widely believed
      to have etiologically distinct subtypes, including subtypes with a genetic basis,
      but no neuroanatomic evidence firmly supports this belief. To date, only one type
      of cerebellar abnormality has been identified in patients with autism: hypoplasia
      of the vermis and hemispheres. By using a large sample of autistic patients and
      healthy volunteers along with precise MR imaging and quantitative procedures, we
      sought to replicate previous reports of cerebellar vermian hypoplasia in autism
      and to identify additional subtypes of cerebellar abnormality. MATERIALS AND
      METHODS: Using MR technology, we imaged and measured posterior and anterior
      vermian regions in 50 autistic patients (2-40 years old) and 53 healthy control
      subjects (3-37 years old). The autistic patients had social, language, cognitive,
      behavioral, and medical history characteristics that were typical of the general
      autistic population. By using precise procedures for positioning and aligning MR
      slices, we obtained comparable MR images within and across subject groups.
      RESULTS: Statistical analyses showed two subgroups of autistic patients, one (86%
      of the patients) with findings consistent with vermian hypoplasia and another
      (12% of the patients) with evidence of vermian hyperplasia. The hypoplasia
      subgroup included 43 patients whose mean midsagittal area for vermian lobules VI
      and VII was 237 +/- 38 mm2, and the hyperplasia subgroup included six patients
      whose mean area was 377 +/- 12 mm2. Thus, the area of lobules VI and VII in the
      hypoplasia subgroup was 16% smaller than the mean area in the control subjects
      (282 +/- 42 mm2) (p < .0001), whereas that in the hyperplasia subgroup was 34%
      larger (p < .0001). Analyses showed that these two subtypes of vermian
      abnormalities were present across all ages of autistic patients studied.
      CONCLUSION: Two different subtypes of autistic patients can be identified on the
      basis of the presence of vermian hypoplasia or hyperplasia as seen on MR images.
      Possible origins for vermian hypoplasia include environmental trauma and genetic
      factors.

PMID- 8273651
TI  - MR imaging of the normal meninges: comparison of contrast-enhancement patterns on
      3D gradient-echo and spin-echo images.
AB  - OBJECTIVE: The purpose of this study was to determine the enhancement pattern of
      the normal meninges on T1-weighted three-dimensional Fourier transform gradient
      echo (3DGE) MR images and to compare this pattern with that observed on
      conventional two-dimensional Fourier transform spin-echo (2DSE) images. This will
      serve as a basis for comparison when cases of suspected meningeal pathology are
      evaluated. SUBJECTS AND METHODS: The appearance of the normal meninges after
      administration of gadopentetate dimeglumine was evaluated on 2DSE and 3DGE images
      in 69 patients who had no known or suspected meningeal abnormality. The total
      percentage of meningeal surface area that underwent contrast enhancement and the
      continuity of meningeal enhancement were evaluated at four anatomic levels.
      RESULTS: In most patients, 2DSE images showed short segments (i.e., < 3 cm) of
      meningeal enhancement, with enhancement of less than 50% of total meningeal
      surface area. However, enhancement of 76-100% of total meningeal surface area was
      routinely observed on 3DGE images, with long segments (i.e., > 3 cm) or
      continuous patterns most frequently observed. The differences between 2DSE and
      3DGE sequences were statistically significant for all regions that were assessed.
      CONCLUSION: Continuous meningeal enhancement or enhancement of long segments of
      normal meninges is routinely observed on contrast-enhanced 3DGE images; this
      appearance differs from those of enhanced 2DSE images and should not be
      interpreted as abnormal.

PMID- 8273652
TI  - MR diagnosis of Creutzfeldt-Jakob disease: significance of high signal intensity
      of the basal ganglia.
AB  - OBJECTIVE: Creutzfeldt-Jakob disease is a rare dementing illness that usually
      affects older adults. Currently, neuroradiologic examinations play a minor role
      in the diagnosis of Creutzfeldt-Jakob disease. Several single case reports have
      noted a distinctive finding of hyperintense signal abnormalities in the basal
      ganglia on T2-weighted MR images of patients with Creutzfeldt-Jakob disease. In
      order to assess the diagnostic utility of this finding, we studied the imaging
      features of four patients with Creutzfeldt-Jakob disease in whom this MR finding
      was present. MATERIALS AND METHODS: Two neuroradiologists retrospectively
      reviewed the MR images of four patients who had pathologically proved Creutzfeldt
      Jakob disease and signal abnormalities in the basal ganglia on T2-weighted MR
      images. The patients' clinical findings were also analyzed. RESULTS: The four
      patients had MR examinations between 6 months and 1 year after the onset of
      symptoms. In all four cases, the hyperintense signal abnormalities in the basal
      ganglia on T2-weighted images were diffuse and bilaterally symmetric. The T1
      weighted images were normal. A CT scan was obtained on a single patient and was
      normal. CONCLUSION: Although a lack of signal abnormality in the basal ganglia on
      MR imaging cannot be used to rule out a diagnosis of Creutzfeldt-Jakob disease,
      our experience and review of published reports suggest that in the proper
      clinical setting, bilaterally symmetric, diffuse hyperintense abnormalities in
      the basal ganglia on T2-weighted images may be a specific sign of Creutzfeldt
      Jakob disease.

PMID- 8273653
TI  - Cerebral paragonimiasis in early active stage: CT and MR features.
AB  - OBJECTIVE: Diagnosis of cerebral paragonimiasis in its early active stage is
      important because curative chemotherapy is possible. Accordingly, this study was
      undertaken to evaluate the CT and MR features of early active cerebral
      paragonimiasis. MATERIALS AND METHODS: We retrospectively reviewed the CT scans
      (n = 29) and MR images (n = 7) of the brain in 20 patients between 7 and 59 years
      old who had cerebral paragonimiasis in the early active stage. The diagnosis was
      based on a positive antibody test by enzyme-linked immunosorbent assay (ELISA)
      for paragonimiasis in serum and CSF. The diagnosis was confirmed surgically in
      seven patients. RESULTS: The most common and characteristic imaging finding was a
      conglomerate of ringlike enhancing lesions (grape-cluster appearance) with
      surrounding edema in one cerebral hemisphere in 11 patients (55%). Other
      nonspecific findings included a solitary ringlike lesion (n = 4) or irregular
      enhancing lesions (n = 2), localized hemorrhage with (n = 3) or without (n = 2)
      enhancing lesions, and a poorly defined non-hemorrhagic, nonenhancing lesion (n =
      1). CONCLUSION: CT and MR findings of clustered ring-enhancing lesions, seen in
      approximately half of the cases of early cerebral paragonimiasis, are suggestive
      of cerebral paragonimiasis.

PMID- 8273654
TI  - MR diagnosis of paraganglioma of the head and neck: value of contrast
      enhancement.
AB  - OBJECTIVE: Contrast enhancement with gadopentetate dimeglumine has been advocated
      to increase the efficacy of MR imaging for paragangliomas of the head and neck.
      However, contrast media are expensive, time-consuming to use, and involve minimal
      but not negligible risks. The purpose of this study was to determine if the use
      of contrast material is warranted in patients undergoing MR imaging for the
      diagnosis of paragangliomas of the head and neck. MATERIALS AND METHODS:
      Unenhanced MR images were compared with images obtained after administration of
      gadopentetate dimeglumine in 23 healthy subjects and 37 patients who had a total
      of 71 tumors. Three combinations of sequences were reviewed independently and in
      a random order by four observers who had no clinical information. Combination A
      comprised enhanced and unenhanced T1-weighted sequences, combination B comprised
      unenhanced T1- and T2-weighted sequences, and combination C was a combination of
      all sequences. A four-point scale of certainty was used. CT, scintigraphic,
      angiographic, and surgicopathologic findings were used as the standard of
      reference. Results were subjected to alternative free-response receiver-operating
      characteristic (AFROC) scoring and statistical analysis. RESULTS: The mean areas
      under the AFROC curve for combinations A, B, and C were 0.761, 0.856, and 0.827,
      respectively. Mean sensitivity/specificity values after dichotomizing the scoring
      results were 0.73/0.94, 0.79/0.95, and 0.78/0.94 for combinations A, B, and C,
      respectively. The performance of combinations B and C did not differ markedly,
      but both combinations were significantly better than combination A. In a
      relatively large percentage (36%) of small postoperative tumor residues not
      detected on unenhanced images, however, gadopentetate dimeglumine allowed
      detection. CONCLUSION: The results of this study indicate that, in general, the
      use of gadopentetate dimeglumine is not necessary for the detection of head and
      neck paragangliomas. The addition of contrast-enhanced imaging does not increase
      the sensitivity or specificity compared with imaging without enhancement. Only
      when searching for small postoperative tumor residues is the addition of
      gadopentetate dimeglumine warranted.

PMID- 8273655
TI  - Aspergillosis of the brain and paranasal sinuses in immunocompromised patients:
      CT and MR imaging findings.
AB  - OBJECTIVE: With the increased survival of patients with severe immunosuppression,
      it has become more important to recognize the various forms of cerebral and
      craniofacial aspergillosis. Currently, only small series of patients with this
      infection have been described; the radiographic diagnosis of cerebral and
      craniofacial aspergillosis has varied and has been relatively nonspecific. The
      purpose of our study was to identify neuroimaging patterns in patients with
      cerebral and craniofacial aspergillosis. Recognition of radiographic patterns of
      aspergillosis may facilitate earlier radiologic diagnosis and prompt therapy.
      MATERIALS AND METHODS: The imaging and clinical data of eight immunosuppressed
      patients with cerebral aspergillosis and one patient each with aspergillosis of
      the orbit, paranasal sinus, and calvaria were evaluated retrospectively. All
      patients were at risk of developing infection by virtue of poorly controlled
      diabetes or other types of congenital or acquired immunosuppression (e.g.,
      steroids, chemotherapy). Patients were selected for study if the diagnosis of
      aspergillosis was established by means of biopsy or autopsy and CT scanning or MR
      imaging was available for review. CT scans and MR images were compared by two
      experienced neuroradiologists, who were aware of the diagnosis of aspergillosis,
      to see if common radiographic patterns could be identified that could be used as
      predictors of this type of infection. RESULTS: Five patients with cerebral
      aspergillosis had multiple ring-enhancing lesions consistent with abscesses.
      Characteristic findings were multiple lesions, an irregular ring of contrast
      enhancement, and hypointensity of the ring on T2-weighted MR images. Three
      patients had cortical and subcortical hypodensities on CT scanning or
      hyperintensities on MR imaging consistent with cerebral cortical and subcortical
      infarction. Two of these three had superimposed hematoma formation. Three
      patients had craniofacial aspergillosis. One patient each had enhancing mucosal
      thickening of the paranasal sinus with secondary intracranial dural enhancement,
      abnormal enhancement of the optic nerve and sheath with infiltrating enhancing
      soft tissue within the intraorbital fat, and an enhancing diploetic lesion of the
      calvaria with underlying dural enhancement. CONCLUSION: Three different
      neuroimaging patterns of cerebral aspergillosis were identified in
      immunosuppressed patients. The first pattern was multiple areas of hypodensity on
      CT scans or hyperintensity on T2-weighted MR images involving the cortex and/or
      subcortical white matter consistent with multiple areas of embolic infarction.
      This pattern could be seen with or without superimposed hemorrhage, identified as
      hyperdensity on CT scans or as hyperintensity on T1-weighted MR images. The
      second pattern was multiple intracerebral ring-enhancing lesions consistent with
      abscesses. The ring was irregular and of low signal on T2-weighted MR images. The
      third pattern was dural enhancement associated with enhancing lesions in the
      adjacent paranasal sinus structure or calvaria or dural enhancement of the optic
      sheath with associated optic nerve and intraorbital fat enhancement. Recognition
      of these three patterns of aspergillosis in immunosuppressed patients may lead to
      more effective diagnosis and treatment planning.

PMID- 8273656
TI  - Sonography in optic disk drusen: imaging findings and role in diagnosis when
      funduscopic findings are normal.
AB  - OBJECTIVE: Optic disk drusen are relatively benign lesions of the eye but can
      cause visual symptoms and may occasionally mimic papilledema on funduscopy. We
      studied the range of sonographic findings and determined if sonography can be
      used to diagnose this condition in the absence of typical funduscopic findings.
      SUBJECTS AND METHODS: Sonography of the eyes was performed in 12 patients with
      known or suspected optic disk drusen by using a 10-MHz transducer. Optic disk
      drusen were diagnosed clinically in 16 of the 24 eyes. The funduscopic appearance
      was typical in 11 eyes and atypical in five eyes. In these five patients, the
      diagnosis was made on the basis of an abnormal appearance of the disk and either
      a strong family history of drusen (four patients) or funduscopic findings that
      were typical of drusen in the opposite eye (one patient). RESULTS: The head of
      the optic nerve was abnormal in 19 of 24 eyes on sonography and in 16 on
      funduscopy. In all cases with abnormal findings on sonograms, an ovoid echogenic
      lesion was evident at the junction of the retina and the optic nerve. The lesions
      varied in size from 1.5 to 4.0 mm in diameter and from 1 to 3 mm in thickness and
      projected posteriorly rather than into the vitreous body. Calcification was
      evident on sonograms in 16 cases. The degree of acoustic shadowing was
      proportional to the size of the echogenic focus. In the three cases in which
      funduscopic findings were normal, sonography showed small drusen deposits. In the
      five eyes that showed disk abnormality but were not typical of drusen on
      funduscopy, sonography showed lesions of varying size; cases with typical
      funduscopic appearances tended to show large lesions on sonography. CONCLUSION:
      Optic disk drusen can be diagnosed on the basis of their typical sonographic
      appearance even in the absence of typical funduscopic findings. Optic disk drusen
      may be seen incidentally when sonograms are made for other conditions, and the
      finding should not be confused with more serious lesions of the optic nerve.

PMID- 8273657
TI  - Sialography: a simple cannulation method.

PMID- 8273658
TI  - MR imaging of biliary cysts in children with biliary atresia: clinical
      associations and pathologic correlation.
AB  - OBJECTIVE: We used MR imaging to determine the prevalence of biliary cysts in
      children with end-stage biliary atresia and evaluated the association of cysts
      with cholangitis, choleretic therapy, portoenterostomy, biochemical
      abnormalities, and MR findings of end-stage liver disease. The MR features of
      these cysts were correlated with their gross and histopathologic appearances.
      MATERIALS AND METHODS: We retrospectively reviewed 48 MR studies, clinical
      history, and laboratory data of 44 consecutive children with biliary atresia.
      RESULTS: MR images showed cysts in eight patients (18%). Cysts were statistically
      (p < .04) more common in patients who had a history of cholangitis, but were not
      associated with choleretic therapy or portoenterostomy surgery. Cysts were not
      statistically correlated with abnormalities in hepatic biochemical function or MR
      features of end-stage liver disease. Four livers with cysts were available for
      histopathologic study. Cysts were filled with bile, and most had an epithelial
      lining, consistent with a biliary origin. The epithelium was frequently
      ulcerated, accompanied by periportal extravasation of bile and inflammation.
      These findings suggest chronic obstruction with microscopic perforation.
      CONCLUSION: Biliary cysts are common in biliary atresia and may be related to
      previous episodes of cholangitis with attendant obstruction of biliary radicles.
      The presence of these cysts did not correlate with hepatic function,
      portoenterostomy surgery, or the extent of liver disease.

PMID- 8273659
TI  - Radiation exposure and efficacy of exposure-reduction techniques during cardiac
      catheterization in children.
AB  - OBJECTIVE: The purpose of this study was to measure radiation exposure levels in
      children undergoing cardiac catheterization. This information was used to assess
      methods of reducing exposure and to characterize total exposures. SUBJECTS AND
      METHODS: The radiation exposure area product was determined for a total of 175
      patients during three study intervals over 10 years. Examinations included
      biplane fluoroscopy and cineangiography for the diagnosis and treatment of
      congenital heart disease. RESULTS: The use of pulsed progressive fluoroscopy was
      found to reduce patients' fluoroscopic exposure rates by approximately 40% as
      compared with interlaced mode fluoroscopy. Combining exposures from the frontal
      and lateral projections, the median fluoroscopic time for diagnostic procedures
      was 21 min and the median time for cineangiography was 42 sec. Median total
      exposure area product was 2063 R-cm2 with cineangiography accounting for 44% of
      the total exposure. For an estimated X-ray beam entrance area of 50-100 cm2, the
      median total entrance exposure was in the range of 20-40 R. Fluoroscopy times for
      interventional procedures were found to be 1.5 to 2.5 times longer than for
      diagnostic procedures, with total exposures approximately three times higher.
      CONCLUSION: This study suggests that pulsed progressive fluoroscopy is an
      effective method of reducing radiation exposure in children undergoing cardiac
      catheterization.

PMID- 8273660
TI  - The value of duplex sonography after peripheral artery angioplasty in predicting
      subacute restenosis.
AB  - OBJECTIVE: The purpose of this study was to determine if abnormal findings on
      duplex sonographic examination after peripheral artery angioplasty correlate with
      the subsequent recurrence of a stenosis. SUBJECTS AND METHODS: We used duplex
      sonography to examine 35 stenoses in 23 patients within 48 hr after the patients
      had angioplasty to treat these stenoses. Patients were followed up for 3 years by
      using one or more of the following: assessment of signs and symptoms, monitoring
      of peripheral pulses, pulse volume recordings, and angiography. Life tables were
      constructed to compare long-term patency with the presence of abnormal findings
      seen on duplex sonograms. Abnormal findings at the dilated segment included a
      blood-flow velocity greater than 120 cm/sec or a residual elevated velocity ratio
      greater than 1.4 or 2.0 immediately after angioplasty. RESULTS: Twelve (34%) of
      35 angioplasty sites showed recurrent stenosis before 36 months. Patency at 24
      months was calculated for velocities less than 120 cm/sec vs velocities of 120
      cm/sec or greater (41% vs 68%), for velocity ratios less than 1.4 vs ratios of
      1.4 or greater (63% vs 57%), and for velocity ratios less than 2.0 vs ratios of
      2.0 or greater (54% vs 74%). We found no significant difference in patency
      between those patients with normal findings and those with abnormal findings on
      duplex sonographic examination after angioplasty. CONCLUSION: Abnormal findings
      on duplex sonograms obtained immediately after peripheral angioplasty cannot be
      used to predict subacute restenosis.

PMID- 8273661
TI  - Femoropopliteal angioplasty: can we predict success with duplex sonography?

PMID- 8273662
TI  - Variable color Doppler appearance of pseudoaneurysm in pancreatitis.

PMID- 8273663
TI  - Injuries associated with MR imaging: survey of safety records and methods used to
      screen patients for metallic foreign bodies before imaging.
AB  - OBJECTIVE: The purpose of this study was to survey the methods used by academic
      institutions for identifying patients who might have metallic foreign bodies or
      other contraindications to MR imaging. We also sought to determine the types of
      MR-related injuries and any subsequent legal action that might have occurred at
      these institutions. MATERIALS AND METHODS: A survey on these issues was mailed to
      207 academic institutions listed in the American Medical Association's Directory
      of Graduate Medical Education Programs. Institutions that did not respond by mail
      were contacted by phone. The survey requested information on the use of
      questionnaires, plain radiography, CT, and metal detectors for screening
      potential MR imaging subjects, as well as on any MR-related injuries and
      subsequent legal action. Responses were entered into a data base and response
      percentages were calculated for each question. RESULTS: The overall response rate
      for the survey was 99% (206/207). These 206 institutions have a total of 368 MR
      imaging units, with a mean number of 1.8 MR units per department (range, none to
      nine). Data from a total of 205 different sites revealed that all patients are
      screened before MR imaging with a written questionnaire at 93% of all
      institutions (190/205). For selected indications, 85% of departments (174/205)
      screen with plain film radiography of the orbits. For selected indications, 41%
      of facilities (83/205) screen with CT of the orbits. Patients are sometimes
      screened with a metal detector or magnetometer in 12% of the departments
      (24/205). Ten departments reported serious injuries relating to MR imaging. The
      most serious injury occurred when an oxygen tank near the magnet became a missile
      and struck a patient's face. Most injuries (nine of 14) were burns. Two
      institutions also reported adverse reactions to gadopentetate dimeglumine.
      Injuries prompted legal action against four of the 10 institutions. No injuries
      were related to intraorbital foreign bodies, vascular clips, or pacemakers in
      patients. CONCLUSION: These data demonstrate the lack of consensus on screening
      protocols before MR imaging. Accidents are uncommon, but most accidents that do
      occur are potentially severe and easily preventable. We recommend that all
      patients be screened by a written questionnaire followed by oral questioning
      before imaging to determine those who are at risk. Specific questions should
      investigate the possibility that patients have ferromagnetic foreign bodies or
      implants anywhere in the body that are electrically, magnetically, or
      mechanically activated. All facilities must maintain a high state of vigilance in
      an effort to prevent iatrogenic burns and injuries from ferromagnetic missiles.

PMID- 8273664
TI  - When should third-party payers provide reimbursement for MR angiography of the
      carotid arteries?

PMID- 8273665
TI  - Patient screening prior to MR imaging: a practical approach synthesized from
      protocols at 15 U. S. medical centers.
AB  - The article by Boutin et al. [1] in this issue of the AJR documents a
      surprinsingly great variation in the MR screening procedures used at different
      academic centers throughout the United States. Although considerable literature
      now exists concerning the MR imaging of patients with ferromagnetic implants,
      devices, and foreign bodies [2-4], no uniform screening protocol to identify such
      patients has yet been adopted. The Safety Committee of the Society for Magnetic
      Resonance Imaging (SMRI) has recommended that "each imaging site should develop a
      standardized policy for screening patients with suspected metallic foreign
      bodies" [5]. To date, however, the SMRI has neither proposed nor endorsed a
      specific screening protocol for general use.

PMID- 8273666
TI  - MR lymphography with superparamagnetic iron nanoparticles in rats: pathologic
      basis for contrast enhancement.
AB  - OBJECTIVE: The purpose of this study in rodents was to determine the pathologic
      basis for enhancement patterns of hyperplastic and tumours lymph nodes shown by
      MR lymphography after IV injection of superparamagnetic iron oxide nanoparticles
      (AMI-227). MATERIALS AND METHODS: Hyperplastic and tumorous lymph nodes were
      imaged in vivo at 1.5 T 1 day after IV administration of AMI-227 (40-200 mumol
      Fe/kg) to rats. Inguinal and axillary lymph nodes were surgically resected, and
      in vitro imaging was done by using the same magnet with a prototype coil that
      allowed a pixel size of 70 x 230 microns. Imaging findings were correlated with
      histologic findings and iron staining of the nodes. RESULTS: With all sequences,
      at doses of 80 mumol Fe/kg or higher, the signal intensity of hyperplastic nodes
      was lower than on unenhanced images. The same pattern was seen in the remaining
      normal tissue of tumourous lymph nodes. This T2* effect was a result of clustered
      particles inside macrophages in the lymphatic sinuses. At doses of 200 mumol/kg,
      the tumor itself consistently showed an increase in signal intensity on T1
      weighted images. This T1 effect probably resulted from particles leaking into the
      interstitial spaces of the tumor. CONCLUSION: After IV injection of
      superparamagnetic nanoparticles, a decrease in signal intensity indicates active
      uptake of particles into macrophages, whereas an increase in signal intensity
      indicates altered capillary permeability in tumor. These findings in rats may
      prove to be clinically useful in the future for differentiating benign from
      malignant enlarged lymph nodes.

PMID- 8273667
TI  - Enhancement of MR angiography with iron oxide: preliminary studies in whole-blood
      phantom and in animals.
AB  - OBJECTIVE: We hypothesized that the previously observed T1 effect of a small
      monocrystalline iron oxide preparation can be exploited to decrease T1 relaxation
      time of blood. Such a decrease, particularly if present for a long time, could be
      used to improve the quality of MR angiograms. To test the hypothesis, we
      performed phantom studies and in vivo animal experiments. MATERIALS AND METHODS:
      The effect of the monocrystalline iron oxide preparation on the MR signal
      intensity (spoiled gradient-recalled acquisition in the steady state pulse
      sequences, various timing parameters) of human whole blood was first tested in a
      phantom (dose range of monocrystalline iron oxide preparation, 0-3 mumol Fe/ml).
      Subsequent experiments were performed in rats (n = 7) and in rabbits (n = 6) to
      determine whether predicted changes in signal intensity could be observed in
      vivo. RESULTS: Dose optimization studies in rats indicate that injected doses of
      15-50 mumol Fe/kg (0.8-2.8 mg Fe/kg) of monocrystalline iron oxide preparation
      resulted in threefold to fourfold increases of aortic signal-to-noise ratio.
      Because of its long plasma half-life (180 min in rats), the iron oxide
      preparation markedly improved the quality of images of the vasculature of the
      lungs, abdomen, and extremities. CONCLUSION: Our experimental results suggest
      that this and possibly other iron oxide preparations are alternatives to
      compounds containing macromolecular gadolinium and could be useful for clinical
      MR angiography.

PMID- 8273668
TI  - The language of the lungs.

PMID- 8273669
TI  - MR imaging of bone marrow lesions: relative conspicuousness on T1-weighted, fat
      suppressed T2-weighted, and STIR images.
AB  - OBJECTIVE: Fat-saturation pulse sequences offer important potential advantages
      for depiction of bone marrow lesions on MR images. The objectives of this study
      were to evaluate the relative conspicuousness of bone marrow lesions on images
      obtained by using two of the most widely available fat-suppression techniques,
      short-TI inversion recovery (STIR) and fat-saturation T2-weighted imaging, and to
      analyze the effect of these methods on image quality. In addition, we sought to
      determine if either or both of these sequences provide significant advantages
      relative to conventional T1-weighted spin-echo images for the evaluation of bone
      marrow lesions. SUBJECTS AND METHODS: T1-weighted (600/15 [TR/TE]), STIR
      (2500/20/160 [TR/TE/TI]), and fat-saturation T2-weighted (2500/20-70) MR images
      were obtained with a 1.5-T system in 34 consecutive patients with suspected bone
      marrow lesions. The conspicuousness of 36 lesions was evaluated subjectively by
      three radiologists, who also evaluated the MR images for how well they showed
      margination and extent of the lesion, image uniformity, motion artifacts, and
      overall image quality. In addition, lesion contrast on these sequences was
      compared quantitatively by using percentage contrast measurements. RESULTS:
      Lesions were qualitatively equally conspicuous with all four pulse sequences.
      Quantitative measurements indicated that lesions were more conspicuous on fat
      saturation T2-weighted and STIR images than on T1-weighted images (p < .001).
      Differences between the first two sequences were not significant. Factors related
      to image quality, including reduction in motion artifacts and image uniformity,
      were generally superior on T1-weighted images. CONCLUSION: T1-weighted, fat
      saturation T2-weighted, and STIR sequences all provide a high degree of
      sensitivity for depiction of most types of bone marrow abnormalities. Although
      the conspicuousness of lesions is similar on fat-saturation T2-weighted and STIR
      images, the former sequence has several practical advantages, including
      acquisition of more slices per unit time and improved tissue specificity. The
      combination of T1-weighted and either fat-saturation T2-weighted or STIR images
      is highly effective for the evaluation of bone marrow lesions.

PMID- 8273670
TI  - Color map of contrast enhancement on MR images: use of desktop computers.
AB  - An alternative method of presenting and evaluating unenhanced and contrast
      enhanced MR images is illustrated. We used a desktop computer and commercially
      available software to combine unenhanced and contrast-enhanced images to produce
      a color map of contrast enhancement superimposed on a gray-scale image. The color
      enhanced images increased the conspicuousness of the areas of contrast
      enhancement, which is particularly important if the enhancing structures are
      small or adjacent to fatty tissues. The process has advantages over standard
      subtraction techniques in that gray scale is preserved while areas of subtle
      contrast enhancement are readily seen as areas of color. Although applied to MR
      imaging, this method may also be applicable to other studies that use contrast
      enhancement.

PMID- 8273671
TI  - University of North Carolina Department of Radiology.

PMID- 8273672
TI  - Fatal reaction after intraarterial injection of nonionic contrast medium.

PMID- 8273673
TI  - The Canadian health care system.

PMID- 8273674
TI  - Squamous cell carcinoma of the larynx in a 29-year-old man with AIDS.

PMID- 8273675
TI  - Diverticulum of the superior vena cava.

PMID- 8273676
TI  - Dynamic MR imaging of the pharyngeal airway in patients with obstructive sleep
      apnea: comments on the technique.

PMID- 8273677
TI  - Screening for colon cancer.

PMID- 8273678
TI  - Hemostatic agent and concomitant abdominal abscess.

PMID- 8273679
TI  - Corticocallosal anomalies in Asperger's syndrome.

PMID- 8273680
TI  - A sinus within a sinus.

PMID- 8273681
TI  - Herald hemiparesis of basilar artery occlusion suggested by Doppler sonography.

PMID- 8273682
TI  - Postangioplasty pseudoaneurysm treated with a vascular stent.

PMID- 8273683
TI  - Radiologic appearance of implantable cardiac defibrillators.
AB  - Since the original descriptions of the radiologic appearance of implantable
      cardiac defibrillators by Lurie et al. [1] and Goodman et al. [2] in 1985, rapid
      growth has occurred in the complexity and variety of models available.
      Originally, all devices were surgically placed in or on the pericardium. Now,
      some devices are inserted by intravascular catheters with part of the device
      buried in the chest wall, avoiding the need for thoracotomy. Initially, these
      devices were used as defibrillators for treatment of tachyarrythmia and
      ventricular fibrillation. Now they serve as pacemakers for both tachy- and
      bradyarrhythmias and can act as cardioverters or defibrillators if required.
      Radiologists must be familiar with the appearances of these devices as their use
      becomes more widespread. In this article, the electrophysiology of these devices
      is briefly reviewed and the typical radiologic appearances are presented along
      with common radiologically recognizable complications.

PMID- 8273684
TI  - Bronchioloalveolar carcinoma causing pulmonary hypertension: a unique
      manifestation.

PMID- 8273685
TI  - The efficacy of specimen radiography in evaluating the surgical margins of
      impalpable breast carcinoma.
AB  - OBJECTIVE: The purpose of this study was to determine if the presence or absence
      of tumor at the surgical margin in cases of impalpable breast carcinoma could be
      predicted accurately with specimen radiography. MATERIALS AND METHODS: We
      obtained single-view radiographs of 119 consecutive surgical biopsy specimens of
      impalpable invasive or in situ ductal carcinoma. Radiographic lesions were
      classified as a mass with moderately well defined margins, a mass with poorly
      defined margins, or microcalcifications without an associated mass. The
      radiographic appearance of the impalpable cancer, the margin as judged from the
      specimen radiograph, the tumor's histologic appearance, and the histologic
      appearance of the tumor margin were then correlated. RESULTS: Specimen
      radiographs showed tumor at the surgical margin in 63 cases; 62 of these were
      confirmed histologically (positive predictive value, 98%). Specimen radiographs
      showed tumor-free surgical margins in 56 cases; 18 of these were confirmed
      histologically (negative predictive value, 32%). These results were independent
      of the radiographic appearance of the lesion or the tumor's histologic
      appearance. CONCLUSION: Decisions based on findings on specimen radiographs were
      valid only if the radiographs showed tumor at the margin of the specimen.

PMID- 8273686
TI  - CT of small-bowel obstruction: value in establishing the diagnosis and
      determining the degree and cause.
AB  - OBJECTIVE: The early diagnosis of small-bowel obstruction is critical in
      preventing complications, particularly strangulation. Traditionally, the clinical
      diagnosis of small-bowel obstruction has depended on plain film confirmation.
      Unfortunately, findings on the plain film may not be confirmatory in 20-52% of
      cases. The purpose of this study was to determine whether CT is superior to the
      traditional clinical-radiographic evaluation in prospectively establishing the
      diagnosis, severity, and cause in cases of suspected obstruction of the small
      bowel and to see what impact this information might have on treatment, costs, and
      the need for additional gastrointestinal contrast studies. SUBJECTS AND METHODS:
      Physicians from three surgical services referred all patients with suspected
      small-bowel obstruction for plain film and CT evaluation. Eight-five patients
      were evaluated on 90 occasions during an 11-month period. Obstruction was
      classified on the basis of clinical and plain film findings as absent,
      indeterminate, or present (partial or complete). CT scans were obtained in all
      patients and were interpreted and graded without knowledge of the clinical
      radiographic classification. The results of gastrointestinal contrast studies
      (barium enema, small-bowel series, and enteroclysis) performed in 21 cases were
      also compared. The gold standard for the diagnosis was surgical findings in 61
      cases and clinical course in 29 cases. RESULTS: On the basis of the combined
      clinical-radiographic findings, the diagnosis was complete obstruction in 21 of
      46 cases (sensitivity, 46%; confidence interval (CI), 32-60%). When CT was used,
      the diagnosis was established in all 46 cases (sensitivity, 100%; CI, 86-100%).
      In the 25 cases in which the traditional evaluation failed, the early CT
      diagnosis of complete obstruction prevented a 12-72 hr delay in surgery with its
      attendant increased morbidity, mortality, and costs. On the basis of the combined
      clinical-radiographic findings, partial obstruction of the small bowel was
      diagnosed in six of 20 cases (sensitivity, 30%), whereas all cases were detected
      with CT. False-positive CT findings for complete obstruction of the small bowel
      occurred in three cases of paralytic ileus (one each due to small-bowel
      infarction, lower lobe pneumonia, and peritonitis due to rupture of the urinary
      bladder). One case of colonic obstruction due to carcinoma in the hepatic flexure
      was mistakenly diagnosed as partial obstruction of the small bowel. The clinical
      and plain film evaluation was never precise enough to provide the exact location
      or cause of small-bowel obstruction. Gastrointestinal contrast studies provided
      additional useful information regarding colonic abnormalities (four cases),
      functional grading of partial obstruction of the small bowel (six cases), and
      exclusion of a false-positive CT diagnosis of complete obstruction in a case of
      reflex ileus. CONCLUSION: CT is sensitive for diagnosing complete obstruction of
      the small bowel and for determining the location and cause of obstruction. In
      comparison, the traditional clinical and plain film evaluation is relatively
      insensitive. CT should be used when the results of clinical and plain film
      evaluation are inconclusive. Gastrointestinal contrast studies play an important
      diagnostic role in partial obstruction of the small bowel and in colonic
      obstruction with predominant small-bowel dilatation.

PMID- 8273687
TI  - Efficacy of CT in distinguishing small-bowel obstruction from other causes of
      small-bowel dilatation.
AB  - OBJECTIVE: Dilatation of the small bowel is a common finding on plain abdominal
      radiographs. In such cases, it is often difficult to determine if the cause of
      the dilatation is small-bowel obstruction, paralytic ileus, or another
      intraabdominal disorder. Accordingly, we studied the efficacy of CT in making
      this distinction. MATERIALS AND METHODS: The medical records of 75 patients with
      small-bowel dilatation seen on CT scans (more than three segments > 2.5 cm in
      diameter) were reviewed. The patients were divided into three groups (obstruction
      [27 patients], other surgical diagnosis [16 patients], and no surgery [32
      patients]) on the basis of clinical course, findings at surgery, or both. CT
      scans were retrospectively evaluated by two gastrointestinal radiologists who did
      not know the results of the chart review. They evaluated the images with regard
      to the following specific criteria for obstruction: presence/continuity of
      duodenal, small-bowel, and colonic dilatation; presence of air-fluid levels;
      amount of intestinal fluid; presence of prestenotic dilatation; presence of
      transition zone; and cause of obstruction. In addition, each radiologist gave an
      overall impression regarding the presence or absence of obstruction (criteria not
      specified to the observers) and its site, or other cause of bowel dilatation. The
      CT interpretations of each of the radiologists were compared with the patients'
      subsequent clinical course. RESULTS: Observer A was correct in 89%, 88%, and 72%
      of cases in the obstruction, other surgical diagnosis, and no surgery groups,
      respectively. Observer B was correct in 78%, 81%, and 69% of cases in the
      obstruction, other surgical diagnosis, and no surgery groups, respectively.
      Observer agreement regarding the proposed criteria for obstruction ranged from
      65% to 91%. For both observers, only the presence of continuous small-bowel
      dilatation, prestenotic dilatation, and a transition zone correlated
      significantly with the presence of small-bowel obstruction. CONCLUSION: CT can be
      a useful test for evaluating small-bowel dilatation and can aid both the
      diagnosis of small-bowel obstruction and its differentiation from other
      conditions resulting in small-bowel dilatation.

PMID- 8273688
TI  - Diaphragmlike strictures of the small bowel associated with use of nonsteroidal
      antiinflammatory drugs.

PMID- 8273689
TI  - Esophagoenteric anastomotic leaks: treatment with fluoroscopically guided balloon
      dilatation.
AB  - OBJECTIVE: Disruption of anastomosis soon after esophagectomy and
      esophagoenterostomy is a relatively common complication that leads to chronic
      enterocutaneous fistulous drainage through the surgical wound in the lower part
      of the neck or upper part of the chest. It is believed that narrowing of the
      anastomosis by postsurgical edema and granulation tissue forces the flow of
      swallowed saliva through the disrupted anastomosis and contributes to the
      maintenance of the leakage. We evaluated the role of fluoroscopically guided
      balloon dilatation for treatment of these esophagoenteric anastomotic leaks.
      MATERIALS AND METHODS: Sixteen consecutive patients with leaking esophagoenteric
      anastomoses in the neck or the upper part of the chest underwent fluoroscopically
      guided dilatations of the anastomosis 7-32 days (mean, 13 days) after surgery
      with 15- or 20-mm angioplasty balloons. Dilatation was done empirically,
      regardless of whether the anastomosis was visibly narrowed. Discharge of
      secretions through the surgical drains in the wounds was measured before and
      after the procedure to determine the response to treatment. RESULTS: In 10
      patients whose anastomoses were leaking for an average of 6 days before the
      balloon dilatation, drainage ceased immediately after the procedure. In four
      patients with leakage averaging 13 days, response to dilatation was delayed;
      drainage continued briefly after the procedure but ceased after an average of 5
      days. In one patient, drainage increased after dilatation but ceased after 4
      days. In another patient, drainage continued for more than 2 weeks after the
      procedure, after which a second dilatation was performed without apparent success
      as drainage persisted for another 10 days. In no case was there evidence of
      further disruption of the anastomosis by the balloon dilatation. CONCLUSION:
      Fluoroscopically guided balloon dilatation appears to be an effective and safe
      technique for treatment of leaking esophagoenteric anastomoses. Early
      intervention seems to increase the effectiveness of the procedure.

PMID- 8273690
TI  - Sonographic diagnosis of acute appendicitis: interpretive pitfalls.
AB  - Graded compression sonography has proven to be of significant clinical value in
      the assessment of patients with right lower quadrant pain and possible
      appendicitis [1-3]. Despite its proven utility, a number of imaging pitfalls must
      be kept in mind when sonograms of the right lower quadrant are interpreted. The
      purpose of this pictorial essay is to illustrate a number of important
      limitations and areas of interpretive difficulty in sonography for appendicitis.

PMID- 8273691
TI  - T2-weighted MR imaging of the abdomen: fast spin-echo vs conventional spin-echo
      sequences.
AB  - OBJECTIVE: The purpose of this study was to compare one optimized T2-weighted
      fast spin-echo sequence with one T2-weighted conventional spin-echo sequence to
      determine the impact of fast spin echo on image quality and diagnostic efficacy
      for evaluation of the abdomen. SUBJECTS AND METHODS: A total of 32 patients with
      43 lesions involving various abdominal organs were examined. T2-weighted fast
      spin-echo (4000/119/4, echo train length = 16, matrix = 256 x 256) and T2
      weighted conventional spin-echo (3400-3800/80/2, matrix = 128 x 256) images were
      compared qualitatively and quantitatively to determine whether the two types of
      images differed with respect to tissue contrast, conspicuousness of lesions,
      image quality, and artifacts. RESULTS: The signal intensity of all abdominal
      structures (except gallbladder and fat) was significantly lower on fast spin-echo
      images than on conventional spin-echo images. Qualitative liver-to-spleen
      contrast was significantly reduced on fast spin-echo images, whereas quantitative
      liver-to-spleen contrast was not significantly different. Blurring of anatomic
      structures, vascular pulsation, and chemical-shift misregistration artifacts were
      significantly reduced on fast spin-echo images. The qualitative conspicuousness
      and contrast-to-noise ratio for all lesions evaluated together were not
      significantly different (p = .5 and p = .069, respectively) on fast spin-echo vs
      conventional spin-echo images. However, qualitative conspicuousness and contrast
      to-noise ratio of solid lesions were significantly reduced on fast spin-echo
      images (p = .022 and p = .01, respectively). The contrast-to-noise ratio of
      cystic lesions was significantly better (p = .002) on fast spin-echo images than
      on conventional spin-echo images. CONCLUSION: Although the fast spin-echo
      protocol used in this study provides better image quality and contrast-to-noise
      ratio for cystic abdominal lesions than does conventional spin echo, the
      qualitative conspicuousness and contrast-to-noise ratio of solid abdominal
      lesions are decreased. Fast spin echo provides high-quality images with fewer
      artifacts in significantly less time than is possible with conventional spin-echo
      images. Further evaluation is necessary to determine the optimal protocol for T2
      weighted fast spin-echo MR imaging of the abdomen.

PMID- 8273692
TI  - Insulinoma: diagnosis with fat-suppressed MR imaging.

PMID- 8273693
TI  - Passive hepatic congestion: cross-sectional imaging features.
AB  - Passive hepatic congestion is caused by stasis of blood within the liver
      parenchyma due to compromise of hepatic venous drainage. It is a common
      complication of congestive heart failure and constrictive pericarditis, wherein
      elevated central venous pressure is directly transmitted from the right atrium to
      the hepatic veins because of their close anatomic relationship (Fig. 1). The
      liver becomes tensely swollen as the hepatic sinusoids dilate and engorge to
      accommodate the backflow of blood. A variety of structural and functional hepatic
      derangements develop that have distinctive appearances on sonograms, CT scans,
      and MR images.

PMID- 8273694
TI  - Mesoblastic nephroma.

PMID- 8273695
TI  - Portal vein thrombosis: imaging findings.
AB  - Portal vein thrombosis (PVT) is usually a complication of pre-existing cirrhosis,
      abdominal malignancy (e.g., pancreatic or hepatocellular carcinoma), or abdominal
      inflammation (e.g., appendicitis, diverticulitis, pancreatitis). Less frequently,
      PVT can be associated with myeloproliferative or connective tissue disorders or
      inflammatory bowel disease [1]. PVT can cause or exacerbate portal hypertension;
      variceal bleeding or hypersplenism may then develop acutely or several years
      later. PVT also complicates portosystemic shunt surgery or hepatic
      transplantation. Unfortunately, the signs and symptoms of PVT can be subtle or
      nonspecific and can be overshadowed by the underlying illness. The radiologist
      may be the only physician to suggest the preoperative or premortem diagnosis of
      PVT. Familiarity with the imaging findings of PVT, therefore, is imperative.

PMID- 8273696
TI  - CT of the iliopsoas compartment: value in differentiating tumor, abscess, and
      hematoma.
AB  - OBJECTIVE: The iliopsoas compartment is an extraperitoneal space defined by the
      iliopsoas fascia; its major components include the iliacus, psoas major, and
      psoas minor muscles. Distinction of neoplastic, inflammatory, and hemorrhagic
      conditions of the iliopsoas compartment is often difficult, whether based on
      clinical evaluation or CT findings. The purpose of this study was to determine
      specific CT features that might help differentiate these three abnormalities.
      MATERIALS AND METHODS: We retrospectively reviewed CT scans of 44 patients who
      had abnormalities of the iliopsoas compartment (15 neoplasms, 21 abscesses, and
      eight hematomas). Final diagnoses were established by surgical biopsy (n = 14),
      percutaneous biopsy (n = 18), or clinical evidence (n = 12). Diagnoses were
      correlated with 11 CT features to determine findings that could be used to
      differentiate the three abnormalities. These included enlargement of the
      iliopsoas muscles; extent, margination, and attenuation of the lesion; presence
      of gas, calcification, bone destruction, fat infiltration, and fascial
      disruption; and associated fluid or adenopathy. The radiologist who interpreted
      the scans had no knowledge of the clinical findings. RESULTS: The most reliable
      CT features for each condition were as follows: irregular margins, 67% sensitive,
      52% specific, and 57% accurate for neoplasms; low attenuation, 100% sensitive,
      43% specific, and 70% accurate for abscesses; and diffuse involvement of the
      entire muscle, 88% sensitive, 78% specific, and 80% accurate for hematomas.
      Combinations of individual CT features did not improve the ability to
      differentiate the three conditions. CONCLUSION: Our results show that the
      efficacy of CT, when scans are interpreted without knowledge of the clinical
      history, is poor for differentiating iliopsoas neoplasms, abscesses, and
      hematomas.

PMID- 8273697
TI  - Voiding cystourethrography after radical prostatectomy: normal findings and
      correlation between contrast extravasation and anastomotic strictures.
AB  - OBJECTIVE: Vesicourethral anastomotic strictures are an important complication of
      radical prostatectomy for prostatic cancer. Their formation has been attributed
      to extravasation of urine at the anastomosis and to the surgical technique used
      to construct the anastomosis. Our study examines whether the formation of a
      vesicourethral anastomotic stricture correlates with (a) contrast extravasation
      seen on postoperative voiding cystourethrograms and (b) the surgical technique
      used to construct the vesicourethral anastomosis. We also describe the
      postoperative appearances of the anastomosis. MATERIALS AND METHODS: One hundred
      and forty-two patients who underwent radical retropubic prostatectomy at our
      institution between June 1, 1987, and December 31, 1991, were included in the
      study. Of these, 101 had a direct end-to-end vesicourethral anastomosis, and 41
      had their anastomosis constructed with traction sutures (Vest procedure). Voiding
      cystourethrograms were obtained 3 weeks after the prostatectomy. The appearance
      of the anastomosis, the presence of extravasation of contrast material at the
      anastomotic site, and the relationship of the subsequent formation of an
      anastomotic stricture to extravasation were evaluated. The influence of the
      surgical technique used to construct the vesicourethral anastomosis on the
      development of anastomotic strictures was analyzed. RESULTS: Contrast
      extravasation at the anastomotic site was seen in 14 (14%) of 101 patients who
      had a direct procedure and in three (7%) of 41 patients who had a Vest procedure.
      No relationship was found between contrast extravasation and subsequent formation
      of a stricture. Anastomotic strictures occurred in 16 (16%) of 101 patients who
      had a direct anastomosis and in 12 (29%) of 41 patients who had a Vest procedure.
      The surgical technique used to construct the vesicourethral anastomosis
      influenced the appearance of the vesicourethral anastomosis on cystourethrograms.
      CONCLUSION: Contrast extravasation at the anastomotic site is not infrequently
      seen on voiding cystourethrograms obtained after radical retropubic prostatectomy
      and resolves with continued drainage via a Foley catheter. As long as catheters
      are left in place until anastomotic healing is complete, extravasation of
      contrast material (implying urine extravasation at the anastomotic site) does not
      influence the subsequent formation of anastomotic strictures. Anastomoses that
      heal more slowly are no more likely to develop strictures than normally healing
      ones. Construction of the vesicourethral anastomosis by using the Vest procedure
      is a significant risk factor for stricture formation.

PMID- 8273698
TI  - MR angiography of occlusive disease of the arteries in the head and neck: current
      concepts.
AB  - MR angiography has many applications in the evaluation of cerebrovascular disease
      (aneurysm, vascular malformation, neoplasm, arterial and venous occlusive
      disease) [1]. Of these, the most common application may be in the assessment of
      arterial occlusive disease in patients at risk for stroke [2]. Consequently, the
      accuracy of MR angiography vs conventional angiography in this assessment will
      most likely determine the extent to which MR angiography is routinely used in
      clinical practice. In this paper, we review the results of clinical trials in
      which MR angiography has been used to evaluate arterial occlusive disease in the
      head and neck and describe those recent developments that promise improved
      visualization of the vasculature.

PMID- 8273699
TI  - Endemic fluorosis of the skeleton: radiographic features in 127 patients.
AB  - OBJECTIVE: A wide range of radiographic appearances have been reported in
      skeletal fluorosis, but little has been written about the spectrum of
      radiographic features. We evaluated the spectrum of radiographic appearances in
      this disorder to help with its diagnosis and differentiation from other metabolic
      skeletal disorders. MATERIALS AND METHODS: One hundred twenty-seven patients with
      clinically proved endemic fluorosis had radiographs of the chest, spine, pelvis,
      elbow, forearm, and knee obtained. The radiographic findings were classified as
      osteosclerosis, osteopenia, intermittent growth lines, diaphyseal widening, or
      soft-tissue ossification. Two different osteopenic patterns were defined: an
      osteoporotic pattern with overall decreased bone density and an osteomalacic
      pattern that combines the features of osteoporosis with bone deformity. Soft
      tissue ossification included involvement of ligaments, tendons, and interosseous
      membranes. RESULTS: Ninety-eight of the patients (89% of the adults) had some
      evidence of calcification and/or ossification of the attachments of ligaments,
      tendons, muscles, and interosseous membranes. Osteosclerosis was seen in 54
      patients (43%), and osteopenia was seen in 51 patients (40%). Of the patients
      with osteopenia, the osteoporotic pattern was seen in 28 and the osteomalacic
      pattern in 23. Growth lines were found in 89 patients (70%). Metaphyseal
      osteomalacic zones were found in children. Diaphyseal widening was present in 35
      patients (28%). CONCLUSION: Endemic skeletal fluorosis can have a wide variety of
      radiographic appearances, including calcification and/or ossification of the
      attachments of soft-tissue structures to bone, osteosclerosis, osteopenia, growth
      lines, and metaphyseal osteomalacic zones.

PMID- 8273700
TI  - Severity of articular cartilage abnormality in patients with osteoarthritis:
      evaluation with fast spin-echo MR vs arthroscopy.
AB  - OBJECTIVE: The purpose of this study was to assess the accuracy of fast spin-echo
      MR imaging for depicting the severity of articular cartilage abnormalities in
      patients with osteoarthritis. SUBJECTS AND METHODS: Twenty-three subjects (10
      volunteers less than 35 years old and 13 patients with proved, symptomatic,
      idiopathic osteoarthritis of the knee of 6 months' to 10 years' clinical
      duration) underwent fast spin-echo MR imaging of the knee. Two observers graded
      each articular surface using a five-category scale that took into account
      abnormalities in the signal intensity of cartilage as well as thickness and
      contour. The 13 patients also underwent arthroscopic evaluation (as part of a
      separate protocol) in which cartilage abnormalities were graded by using a
      similar five-category grading scale, without the graders knowing the results of
      MR imaging. Articular cartilage was assumed to be normal in the volunteers.
      RESULTS: One hundred thirty-seven joint surfaces were graded; one surface was
      obscured by artifact and was excluded. The Spearman rank linear correlation
      between arthroscopic and MR grading was highly significant (p < .002) for each of
      the six articular regions evaluated. The MR and arthroscopic grades were the same
      in 93 (68%) of 137 joint surfaces, they were the same or differed by one grade in
      123 surfaces (90%), and they were the same or differed by one or two grades in
      129 surfaces (94%). CONCLUSION: Our results suggest that fat-presaturated fast
      spin-echo MR imaging depicts the severity of articular cartilage abnormalities in
      osteoarthritis with reasonable accuracy, as compared with arthroscopic evaluation
      as the standard of reference.

PMID- 8273701
TI  - The winds of change.

PMID- 8273702
TI  - A description of mothers' questions to their young deaf children during storybook
      reading.
AB  - The frequency and types of questions that four hearing mothers used with their 3-
      and 4-year-old deaf daughters was examined. Relationships between frequency and
      type of question and child mean length of utterance (MLU) measurements were also
      explored. Results indicated that the mothers used fewer questions than hearing
      mothers of hearing children but that the types of questions used were similar.
      Three mothers used text-related indirect commands, a question type not examined
      frequently in previous research. Child MLU measurements appeared to influence the
      amount and types of questions mothers used, although MLU, as measured in this
      study, may not have been a valid descriptor of the children's expressive
      language. Implications for the quality of language during joint book reading with
      young deaf children are discussed.

PMID- 8273703
TI  - Bi-Bi to MCE?
AB  - In the past few years, we have witnessed the introduction of a bilingual
      bicultural approach and an increasing skepticism of the value of manually coded
      English in the education of deaf children. The thrust of bilingual-bicultural
      programs is emphasis on using American Sign Language as the primary language of
      instruction. However, merely advocating something (i.e., the use of American Sign
      Language) in no way guarantees its successful implementation. This paper reviews
      the research on past usage of manually coded English in the classroom for clues
      as to some of the concerns that American Sign Language might face in its
      implementation.

PMID- 8273704
TI  - What deaf and hard-of-hearing adolescents know and think about AIDS.
AB  - AIDS is a major problem for current and future generations. Lack of information
      about it, including how it is transmitted and how it can be prevented, places
      adolescents at risk. This study focused attention on the knowledge and opinions
      of deaf and hard-of-hearing adolescents on the topics of HIV and AIDS. The
      results suggest that the adolescents who participated in the study had a general
      idea about what they are, as well as the potential impact of the disease.
      However, they demonstrated important gaps in their knowledge of how HIV and AIDS
      are transmitted and prevented, and who can get AIDS. We recommend greater
      educational attention to the topic, given the harsh reality that adolescence may
      well be the primary time period for infection, even though the symptoms may not
      appear until many years later.

PMID- 8273705
TI  - The challenge of attention deficit disorder in children who are deaf or hard of
      hearing.
AB  - Attention Deficit Disorder is a common cause of school problems. Yet, the
      condition has not been examined extensively in children who are deaf or hard of
      hearing. In this article, the varying manifestations and subgroups of the
      condition and its impact on the behavior and performance of these children are
      discussed. Its prevalence is examined by a review of the literature and an
      analysis of studies at a state residential school for the deaf. In this
      population, the prevalence appears to be similar to that reported in hearing
      children; however, some subgroups of deaf children, such as those with acquired
      hearing loss, are at greater risk. Recent legislative initiatives concerning the
      condition are discussed, as are challenges for managing the problem and
      directions for future research.

PMID- 8273707
TI  - How hard-of-hearing and deaf children learn their names.
AB  - Data from a qualitative study on the literacy development of preschool hard-of
      hearing and deaf children were analyzed to discover how the children learned to
      read, write, and spell or fingerspell their names. The research was conducted for
      9 months in two preschool classes for hard-of-hearing and deaf children. Four
      hard-of-hearing and three deaf children participated. Data sources included
      extensive descriptive and interpretive field notes on classroom observations of
      the children, and drawing and writing samples from the children. Analysis
      revealed that the children learned that names are powerful expressions of
      identity through teacher demonstrations, immersion in a literacy-rich
      environment, and numerous opportunities to explore written language.

PMID- 8273706
TI  - Evaluating and managing attention deficit disorder in children who are deaf or
      hard of hearing.
AB  - Effective management of children who are deaf or hard of hearing and faced with
      the added challenge of Attention Deficit Disorder requires a comprehensive and
      coordinated spectrum of services. A complex array of underlying or associated
      factors can mimic, cause, or exaggerate the symptoms. Careful diagnosis is thus
      essential and is the prerequisite for developing effective intervention. In this
      article, we present a practical approach to the problem, based on experience with
      a model treatment program at a residential school for the deaf. Suggestions are
      provided regarding the diagnostic work-up of children presenting with attention
      problems. Management approaches are discussed for the classroom, home, and
      residential area as well as specialized therapeutic intervention and the use of
      medication. A model for implementing a treatment program in a school is
      presented, and future challenges are discussed.

PMID- 8273708
TI  - Acquisition and generalization of social behaviors in language-disabled deaf
      children.
AB  - In the present study, the effectiveness of a multifaceted training package on the
      acquisition and generalization of three social behaviors--initiating interaction,
      interacting with others, and turn waiting--was assessed with nine 12- and 13-year
      old language-disabled deaf children. The package included (1) child training and
      (2) supervision, feedback, and goal-setting by teachers and residential staff
      members. Steps were taken to promote generality of the effects and the social
      validity of the procedures. Data were collected within a multiple baseline design
      across behaviors. Visual inspection and statistical analysis showed that
      instances of appropriate target behaviors increased and were generalized across
      settings, activities, and subjects during the training procedure and that the
      effects were maintained following training.

PMID- 8273709
TI  - Hearing status and language fluency as predictors of automatic word and sign
      recognition.
AB  - In previous studies, evidence concerning the extent of automatic word recognition
      in deaf children and the influence of language fluency on word and sign
      recognition (as indexed by the Stroop task) has been contradictory. This study
      examined the effects of English and sign language fluency in the automatic word
      and sign recognition of deaf and hearing adults. Results indicated that
      responding in sign took longer and created more Stroop interference than
      responding orally. Two groups of certified interpreters revealed this finding to
      be independent of hearing status. Most important, deaf subjects showed greater
      automaticity in recognizing signs than words, whereas hearing subjects showed
      greater automaticity in recognizing words than signs. This pattern was unaffected
      by language fluency. The findings clarify the results of previous studies both
      theoretically and methodologically.

PMID- 8273710
TI  - Esophagogastroduodenoscopy for the family physician.
AB  - Esophagogastroduodenoscopy is most commonly performed for evaluation of
      epigastric pain, severe heartburn, chronic nausea and other dyspepsia syndromes
      that are not relieved by medical therapy. It should not be performed as an in
      office procedure in patients with unstable angina, respiratory failure, active
      upper gastrointestinal bleeding or hemodynamic instability. Although office
      esophagogastroduodenoscopy is safe for low-risk patients, the risks associated
      with anesthesia and the need for postprocedure observation may require other
      patients to undergo the procedure in a hospital setting. Use of a local
      anesthetic throat spray reduces the gag response that occurs when the endoscope
      is swallowed. Sedation is commonly achieved with intravenous administration of a
      benzodiazepine plus a narcotic, and the effects of these drugs can be rapidly
      reversed. Complications are rare and most frequently result from medications
      rather than from the procedure itself.

PMID- 8273711
TI  - Childhood sexual abuse.
AB  - Childhood sexual abuse is a common problem. Patients with subacute and nonacute
      injuries may be treated in the physician's office. Patients with acute injuries
      are usually best managed in an emergency department where forensic testing can be
      performed efficiently. Physicians need to know how to appropriately interview
      children with signs of acute and subacute trauma. The physical examination should
      be thorough, nontraumatic and well documented. Evidence of inflammation,
      infection, and acute or healed trauma should be sought. Attention should be paid
      to sexually transmitted diseases, pregnancy prevention and mental health needs.
      Coordination with child welfare services, mental health professionals and law
      enforcement officers is often indicated. Awareness of the various presentations
      of sexual abuse and familiarity with normal and abnormal genital findings are
      necessary for the initial evaluation of these children.

PMID- 8273712
TI  - Health care for the homeless: a family medicine perspective.
AB  - Many factors contribute to the health problems of homeless persons, including
      exposure to adverse weather, trauma and crime, overcrowding in shelters, unusual
      sleeping accommodations, poor hygiene and nutritional status, alcoholism, drug
      abuse and psychiatric illness. It is common for homeless adults to have skin
      ailments, respiratory infections, traumatic injuries and chronic
      gastrointestinal, vascular, dental and neurologic disorders. Homeless children
      may have respiratory, ear and skin diseases, as well as special problems,
      including failure to thrive, developmental delay, neglect and abuse. Important
      questions to ask during history-taking include questions about sleeping
      conditions, sources of food, past psychiatric problems and substance abuse, and
      sources of social support. Special attention should be given to examination of
      the skin, teeth and feet. Supplemental food, immunizations, psychologic
      counseling and social service referrals should be considered for homeless
      pediatric patients.

PMID- 8273713
TI  - Falls in the elderly.
AB  - Falls in the elderly are a common problem with potentially serious consequences.
      Elderly persons who fall may incur physical injuries that result in
      hospitalization or even institutionalization. Fear of falling may cause the
      elderly to restrict their activities and become socially isolated. A fall is
      usually the result of a combination of factors involving the patient and the
      environment. A patient's risk of falls may be assessed on the basis of a complete
      history, including a drug review and an evaluation of the patient's environment,
      as well as a thorough physical examination with emphasis on neurologic components
      and functional performance. Correction or adjustment of even a few of these risk
      factors may allow the elderly patient to avoid falls.

PMID- 8273714
TI  - Nondrug treatment of anxiety.
AB  - Anxiety is the most common mental health problem in the United States. Most
      patients with anxiety seek treatment from primary care physicians, who are
      generally familiar with the pharmacologic management of anxiety. However, many
      problems are associated with the use of antianxiety medications, and increasing
      evidence shows that certain nondrug strategies are effective, particularly in
      patients with mild to moderate symptoms. The key features of nondrug treatment
      can be summarized under the mnemonic "A-E-I-O-U." The physician assesses the
      nature and causes of the anxiety; educates the patient about the causes and
      management of anxiety; intervenes by teaching specific, effective anxiety-control
      techniques; observes and helps the patient monitor progress and, finally, helps
      the patient achieve understanding of anxiety and ways to prevent recurrence.

PMID- 8273715
TI  - Diagnosis, treatment and prognosis in patients with low back pain.
AB  - Patients with chronic low back pain can present a treatment dilemma for the
      family physician. Low back pain is one of the most common symptoms bringing
      patients to physicians. Despite its high prevalence, low back pain is often
      difficult to treat. In most patients, the pain cannot be pinpointed at a specific
      anatomic lesion, and plain radiographs, computed tomographic scans and magnetic
      resonance imaging studies are not useful. While most people with low back pain
      improve regardless of the type of intervention, some evidence shows that McKenzie
      exercises, manipulation and injection therapy are helpful for patients who do not
      recover spontaneously.

PMID- 8273716
TI  - ACP releases guidelines for the treatment of gallstones.

PMID- 8273717
TI  - Family physicians and homelessness.

PMID- 8273718
TI  - The benefits of smoke-free health care campuses.

PMID- 8273719
TI  - Marching in a new parade: family medicine and health care reform.

PMID- 8273720
TI  - On the lookout for child abuse.

PMID- 8273721
TI  - Concerns about universal hepatitis B immunization.

PMID- 8273722
TI  - Concerns about universal hepatitis B immunization.

PMID- 8273723
TI  - Concerns about universal hepatitis B immunization.

PMID- 8273724
TI  - Intramuscular hemangioma of the gastrocnemius.

PMID- 8273725
TI  - Osteopathic manipulation for lumbar disk disease.

PMID- 8273726
TI  - Diary from a week in practice.

PMID- 8273727
TI  - Malignant melanoma.
AB  - Family physicians should be aware of the early signs of malignant melanoma, as
      well as measures that can be taken to prevent the disease. Etiologic factors for
      melanoma include sunburns, particularly those occurring early in life, giant
      congenital nevi, dysplastic nevi and the presence of numerous nevi. The four
      major subtypes of melanoma are lentigo maligna, superficial spreading melanoma,
      acral lentiginous melanoma and nodular melanoma. Diagnosis is based on
      excisional, incisional or punch biopsy. The crude five-year survival rate for
      malignant melanoma is 81 percent, but survival depends on stage of disease,
      anatomic site, the patient's age and sex, histologic factors and clinical
      subtype. Surgical excision is the usual treatment for primary melanoma. Surgery,
      radiation therapy and chemotherapy are used in the management of metastatic
      disease, but the prognosis following the development of metastases remains poor.
      Family physicians can affect survival rates by improving early detection,
      promoting patient awareness and self-examination, and encouraging regular
      physical examination of patients who are at increased risk of melanoma.

PMID- 8273728
TI  - Therapeutic effects of captopril on ischemia and dysfunction of the left
      ventricle after Q-wave and non-Q-wave myocardial infarction.
AB  - Treatment with angiotensin-converting enzyme inhibitors has a beneficial effect
      on myocardial ischemia and left ventricular dysfunction after myocardial
      infarction. The effect of captopril on myocardial ischemia was evaluated in 58
      patients with left ventricular dysfunction (ejection fraction < 45%) after Q-wave
      or non-Q-wave myocardial infarction in a placebo-controlled, parallel, double
      blind study. Patients were randomized on day 7 to either placebo or captopril (50
      mg daily) and monitoring for a period of 180 days by serial echocardiography and
      ambulatory ST-segment monitoring. There was a significant effect of captopril on
      the duration of ambulatory ST depression during the 180 days: The values per day
      were reduced from 28 +/- 5 min at baseline to 2 +/- 1 min on day 180 in the Q
      wave group (p < 0.01) and from 39 +/- 10 min at baseline to 6 +/- 1 min on day
      180 in the non-Q-wave group (p < 0.05). In the placebo group the duration of ST
      depression on day 180 were 21 +/- 8 min in the Q-wave group and 22 +/- 7 min in
      the non-Q-wave group, thus being significantly higher as compared with the
      corresponding captopril groups (p < 0.01 and p < 0.05, respectively). In the
      placebo Q-wave group there was a significant increase in left ventricular end
      diastolic volume index from 74 +/- 3.5 to 89 +/- 4.5 ml/m2 (p < 0.01) during the
      study period, which was in contrast to unchanged values of 75.5 +/- 3.0 and 75.0
      +/- 3.5 ml/m2 (not significant [NS]) in the captopril Q-wave group.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8273729
TI  - Nitroglycerin infusion during upright tilt: a new test for the diagnosis of
      vasovagal syncope.
AB  - The aim of our present study was to assess the value of nitroglycerin infusion
      during upright posture as a new provocative test for diagnosis of vasovagal
      syncope. To this purpose 40 patients with unexplained syncope (17 men and 23
      women, mean age 47 years) and 25 asymptomatic control subjects with negative
      baseline head-up tilt underwent two other tilting tests, one during nitroglycerin
      infusion and one during isoproterenol infusion. The protocol of the nitroglycerin
      test consisted of a maximum of five successive stages of 5 minutes in the supine
      position plus 10 minutes 80-degree upright tilt at progressively increasing
      infusion rates (increments of 0.86 microgram/kg/hr every stage). During the
      nitroglycerin test a positive response (syncope in association with sudden
      hypotension and bradycardia) occurred in 21 (53%) patients with unexplained
      syncope, an exaggerated response (minor symptoms in association with slowly
      increasing hypotension alone) occurred in 10 (25%), a negative response in 9
      (22%), and drug intolerance in 0. During the isoproterenol test these percentages
      were 25%, 25%, 32%, and 18%, respectively. Only 2 (8%) control subjects had a
      positive response to nitroglycerin test and 2 (8%) to isoproterenol test. Thus
      the nitroglycerin test seems to be a useful alternative tool for diagnosis of
      vasovagal syncope; it is equally specific but more sensitive and feasible than
      the isoproterenol test.

PMID- 8273730
TI  - Reduced parasympathetic cardiac control in patients with hypertension at rest and
      under mental stress.
AB  - The neurogenic component in the pathogenesis of essential hypertension has
      predominantly been analyzed with regard to the sympathetic part of the autonomous
      nervous system; the parasympathetic branch has largely been neglected. We
      investigated whether 54 normotensive (mean causal blood pressure [cBP]: 125 +/-
      6/82 +/- 4 mm Hg), 41 borderline hypertensive (cBP: 134 +/- 8/90 +/- 5 mm Hg),
      and 34 hypertensive men (cBP: 152 +/- 13/101 +/- 5 mm Hg) without secondary
      target organ damage differed in parasympathetic cardiac control. Parasympathetic
      cardiac control was assessed via the amount of fast fluctuations (0.15 to 0.40
      Hz; vagus band) and by the amount of respiratory-linked fluctuations (mean
      respiratory frequency +/- 0.03 Hz) in the power spectra of continuously
      registered interbeat intervals under the following conditions: mean of three rest
      phases with 10, 5, and 5 minutes' duration (REST); mean of two modes of a
      reaction time task with 10 and 5 minutes' duration (RTT); mean of 5 minutes'
      mental arithmetic plus noise (MA). Analysis of variance (ANOVA) shows that
      spectral energy in the so-called vagus band reveals the most prominent
      differences between blood pressure groups under all conditions: REST =
      normotensive, 2.70 +/- 0.31; borderline hypertensive, 2.55 +/- 0.33; and
      hypertensive, 2.43 +/- 0.43 (F[2.126] = 6.19; p < 0.01). RTT = normotensive, 2.41
      +/- 0.35; borderline hypertensive, 2.19 +/- 0.33; and hypertensive, 2.17 +/- 0.46
      (F[2.126] = 6.04; p < 0.01); MA = normotensive, 2.69 +/- 0.34; borderline
      hypertensive, 2.52 +/- 0.33; and hypertensive, 2.38 +/- 0.46 (F[2.126] = 7.04; p
      < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273731
TI  - Normalization of circulating atrial natriuretic peptides in cardiac transplant
      recipients.
AB  - To assess whether heart transplantation (Htx) alters the marked elevation of
      circulating atrial natriuretic peptides usually found in patients with congestive
      heart failure (CHF), 14 subjects (nine with compensated and five with
      decompensated CHF), each with an ejection fraction < or = 28%, were evaluated.
      Immediately before and hourly for the first 12 hours after Htx, then daily for 21
      days and every 1 to 4 weeks for 6 months, the circulating concentrations of the N
      terminus (pro atrial natriuretic factor [ANF] 1-98), midportion of the N-terminus
      (pro ANF 31-67), and C-terminus (that is, ANF) of the 126 amino acid prohormone
      were measured. Increased (p < 0.001) levels of these peptides were found in
      superior vena cava, right atrial, and peripheral venous samples 1 hour after Htx
      in all subjects except one. The atrial natriuretic peptide levels correlated only
      with right atrial pressure (p < 0.01) in the first 24 hours. Circulating
      concentrations of these peptides returned to those of healthy adults between 5
      and 12 days after Htx in 11 out of 14 Htx recipients. Thus successful Htx can
      restore the elevated circulating concentrations of atrial natriuretic peptides to
      those of healthy adults.

PMID- 8273732
TI  - Cardiac troponin T and CK-MB mass release after visually successful percutaneous
      transluminal coronary angioplasty in stable angina pectoris.
AB  - The incidence of cardiac troponin T (Tn-T) and creatine kinase (CK) isoenzyme MB
      mass release was studied in 23 patients with stable angina pectoris undergoing
      visually successful percutaneous transluminal coronary angioplasty (PTCA). Serial
      blood samples were drawn for measurement of serum Tn-T, CK-MB mass, total CK
      activity, CK-MB activity, and lactate dehydrogenase isoenzyme (LD-1). ST segment
      monitoring was carried out during PTCA and for the following 24 hours. None of
      the patients showed electrocardiographic (ECG) evidence of myocardial infarction.
      However, Tn-T was elevated in three patients (0.23 to 1.32 micrograms/L), and in
      these three and an additional three patients CK-MB mass was also elevated (7.0 to
      27.5 micrograms/L). Total CK activity and LD-1 were only elevated in one of these
      six patients. None had elevated CK-MB activity. ST segment depression on ECG
      recording was not predictive of Tn-T or CK-MB mass release. Patients with
      elevated Tn-T or CK-MB mass did not differ with respect to demographic data,
      stenosis characteristics, or in the PTCA procedure. We conclude that CK-MB mass
      uncovers clinically and ambulatory electrocardiographically inapparent severe
      myocardial ischemia/minor myocardial damage (microembolization) in 26% (6 of 23)
      of patients after visually successful PTCA; 13% (3 of 23) had elevated Tn-T,
      indicating minor myocardial damage. The application of these markers in the
      future could be of considerable value for determining the efficacy of coronary
      angioplasty and atherectomy, as well as for drug therapy in connection with such
      procedures.

PMID- 8273733
TI  - Diastolic suction in the human ventricle: observation during balloon mitral
      valvuloplasty with a single balloon.
AB  - Diastolic suction has been demonstrated experimentally as a ventricular negative
      pressure when the ventricle is allowed to relax completely in the absence of
      filling, but it has not been extensively studied in the in vivo human heart. In
      balloon mitral valvuloplasty with a single balloon, the mitral orifice is
      occluded and inflow is considered to be completely obstructed during a balloon
      inflation. To demonstrate diastolic suction in the human ventricle, we measured
      left ventricular pressure during valvuloplasty with a high-fidelity catheter tip
      manometer in 17 patients. Left ventricular pressure fell below zero during a
      balloon inflation in all patients (-2 to -12 mm Hg). The peak negative diastolic
      pressure showed significant correlations with end-systolic volume index (r =
      0.53, p = 0.03) and with the ejection fraction (r = 0.80, p = 0.0001). Thus
      diastolic suction was demonstrated in the human beating heart, and the sucking
      effect was potent in the heart with small end-systolic volume and high-ejection
      fraction.

PMID- 8273734
TI  - Assessment of left ventricular enlargement from planar thallium-201 images.
AB  - Although a subjective assessment of left ventricular (LV) size can be made from
      planar thallium images, the validity of this practice had not been critically
      assessed. The objective of this study was to determine the accuracy of planar
      thallium imaging in the assessment of LV size by using two-dimensional guided M
      mode echocardiographic measurements as the standard. Consecutive patients (n =
      100) who had clinically indicated stress thallium and echocardiography done
      within a time interval of 1 month were selected. LV size was classified as
      dilated or normal on immediate and 4-hour-delayed thallium scans by the consensus
      of two blinded observers. When present, perfusion defects were noted. LV end
      diastolic internal diameter (LVIDd) was measured on M-mode images. The mean LVIDd
      was 5.7 cm in patients with dilated LVs compared with 5.0 cm in those with normal
      LVs (p < 0.01). By using an LVIDd of 5.6 cm as the upper limit of normal, the
      sensitivity and specificity of planar thallium imaging for detection of left
      ventricle enlargement were 87% and 86%, respectively. Corresponding positive and
      negative predictive accuracies in this population were 65% and 96%, respectively.
      There was a higher incidence of fixed defects in group 1 (p < 0.01). We conclude
      that LV enlargement can be easily and reliably determined from routine planar
      thallium images.

PMID- 8273735
TI  - Treatment of chronic Chagas' disease with benznidazole: clinical and serologic
      evolution of patients with long-term follow-up.
AB  - Prescribing etiologic treatment for chronic Chagas' disease is highly
      controversial because of the difficulties involved in assessing its therapeutic
      efficacy--the low degree of parasitemia, the persistence of positive immunologic
      reactions, the lack of clinical findings to support each type of treatment, and
      the necessarily prolonged follow-up of the patient. An 8-year average follow-up
      was performed on 131 patients treated with benznidazole (5 mg/kg/day for 30 days)
      (TP) and 70 untreated patients (UTP) by serial electrocardiograms and analysis of
      the cardiomyopathic progress of the clinical groups, and by immunologic tests at
      both the beginning and end of the study. TPs presented less electrocardiographic
      changes during the follow-up period (4.2% vs 30%) and a lower frequency of
      deterioration in their clinical condition (2.1% vs 17%). The percentage of TPs
      who were serologically negative was 19.1% whereas 6% of the UTPs became
      serologically negative, a result that correlated with a lack of progress in the
      cardiomyopathy. Benznidazole treatment significantly decreased serologic titers,
      signifying parasitologic cure in two patients.

PMID- 8273736
TI  - Coronary angioplasty from the perspective of atherosclerotic plaque: morphologic
      predictors of immediate success and restenosis.
AB  - High restenosis rates continue to plague the overall efficacy of percutaneous
      transluminal coronary balloon angioplasty (PTCA). It is not surprising that
      predictions of long-term success or failure of PTCA based on coronary angiography
      are of limited value because these images provide only a circumscribed view of
      the arterial lumen and offer little insight into underlying plaque morphologic
      characteristics. Coronary atherosclerotic lesions are quite diverse with respect
      to plaque characteristics (eccentricity, concentricity, and extent of fibrosis,
      necrosis, and calcification) and cardiac ischemic syndromes (stable angina,
      unstable angina, myocardial infarction, and sudden cardiac death). It could thus
      be expected that dissimilar plaques will respond differently to balloon
      dilatation, and that plaque morphologic features may play an important role in
      the immediate and long-term outcome after PTCA. Histologic evaluation of de novo
      atherosclerotic plaques underscores the heterogeneity of coronary
      atherosclerosis. From pathologic examination of human coronary arteries subjected
      to PTCA during life, expansion of the arterial circumference via medial damage is
      required for an effective increase in lumen size. Eccentric plaques and plaques
      with a large necrotic core are more likely to be successfully dilated compared to
      concentric, fibrotic lesions. Intravascular ultrasound studies of PTCA have
      supported histologic findings. Restenosis involves the complex interaction of
      growth factors and cytokines, cellular elements (endothelial cells, smooth muscle
      cells, platelets, and inflammatory cells), and the extent of arterial injury. The
      effects of underlying plaque morphologic features on the vascular biology of
      restenosis requires further clarification.

PMID- 8273737
TI  - Early cardiac allograft failure after orthotopic heart transplantation.
AB  - Early cardiac graft failure has been reported to occur in 4-25% of patients
      undergoing orthotopic heart transplantation. To further elucidate the
      characteristics and prognosis of patients with graft failure, we retrospectively
      identified 10 patients from a series of 212 consecutive recipients with
      catastrophic graft dysfunction in the absence of acute cellular rejection, right
      ventricular failure secondary to pulmonary hypertension and technical factors. We
      present a case report and the experience from one transplant center, a review of
      the literature and possible strategies for the management of early graft failure.
      Mean onset of graft failure was 6.5 days (range intraoperative to 23 days).
      Multivariable analysis revealed a longer total ischemic time in patients with
      early graft dysfunction (200 +/- 14 vs. 166 +/- 4 min). No episodes of hyperacute
      rejection were observed. Pathologic changes noted on biopsy or autopsy included
      ischemia in 9 and vascular rejection in 1. The mortality at 60 days was 50%.
      Early use of aggressive mechanical and pharmacological support is described and
      appears to be important for graft salvage.

PMID- 8273738
TI  - In vivo angioscopic visualization of right heart structure in dogs by means of a
      balloon-tipped fiberoptic endoscope: potential role in percutaneous ablative
      procedures.
AB  - We designed an angioscopic system that consisted of a fiberoptic endoscope
      enclosed in a polyurethane thin-wall tube with a latex balloon attached to its
      distal end. In 10 anesthetized closed-chest dogs the angioscope was placed in the
      right heart via a femoral vein. By inflating the balloon with 5 to 10 ml of
      normal saline solution to displace the blood, the endocardial structure of the
      right heart was visualized. Under fluoroscopic guidance and direct vision, an
      ablation catheter was placed inside the coronary sinus or in its vicinity, and
      radiofrequency energy was delivered through the catheter tip to create a lesion.
      The appearance and anatomic location of the lesion and the endocardial structure
      as seen through the angioscope correlated well with the results of postmortem
      examination. There were no or minimal changes in heart rate, blood pressure, or
      cardiac output by inflating the balloon to a volume of 15 ml in the right atrium
      or right ventricular cavity. An inflated balloon may produce single or repetitive
      atrial or ventricular arrhythmias, but not sustained tachyarrhythmia. Our study
      demonstrates that in vivo visualization of the interior of the right heart is
      feasible and that our angioscope can be used to assist placement of catheter at a
      specific location in the right atrium and to verify its location with no or
      minimal hemodynamic effects and without causing significant arrhythmias.

PMID- 8273739
TI  - Microwave thermal balloon angioplasty in the atherosclerotic rabbit.
AB  - We evaluated the angiographic and histologic response of the coronary vessels of
      the atherosclerotic rabbit to microwave thermal balloon angioplasty. Sixteen
      rabbits with atherosclerosis of the external iliac arteries following a high fat
      diet and endothelial denudation were treated with either CBA or MBA. Four weeks
      following angioplasty angiography was repeated, and following the death of the
      animals, the vessels treated were excised for histologic evaluation. In vessels
      with MBA with peak temperatures of 85 degrees C there was an increase in luminal
      diameter immediately postangioplasty, from 1.66 +/- 0.32 mm to 2.54 +/- 0.23 mm
      (p < 0.05). The diameter at 4 weeks (2.29 +/- 0.74 mm) remained increased
      compared with the preangioplasty diameter (p < 0.05). With microwave angioplasty
      at 70 degrees C there was an increase in luminal diameter, from 1.92 +/- 0.37 mm
      to 2.40 +/- 0.22 mm (p < 0.05) immediately postangioplasty. This increase in
      diameter was not sustained at 4 weeks (1.86 +/- 0.28 mm). In the vessels treated
      with CBA there was no significant increase in diameter noted either immediately
      postangioplasty or at 4 weeks postangioplasty. In the thermally treated vessels,
      histologic evaluation revealed a loss of lipid-laden cells; it also revealed the
      formation of a concentric hypocellular fibrotic layer. Microwave thermal balloon
      angioplasty at 85 degrees C results in enhancement of the immediate and delayed
      response to angioplasty. Modification of the proliferative response to
      angioplasty may be accomplished with this modality.

PMID- 8273740
TI  - Induction of neointimal hyperplasia by coronary angioplasty balloon
      overinflation: comparison of feeder pigs to Yucatan minipigs.
AB  - We evaluated the use of simple balloon overinflation to induce neointimal
      hyperplasia in a porcine model of coronary artery restenosis. By using standard
      percutaneous transluminal coronary angioplasty techniques, left anterior
      descending (LAD) and/or left circumflex (LCX) coronary arteries of either
      juvenile feeder pigs or adult Yucatan minipigs were intentionally overinflated.
      Four weeks later, resultant neointimal hyperplastic responses (neointima/media
      area; NI/M) were quantitated morphometrically. At all ballooned sites neointimal
      hyperplasia occurred only when the internal elastic lamina (IEL) was ruptured;
      the degree of hyperplasia correlated directly with the injury index, that is, the
      percentage of IEL circumference that fractured (r = 0.74; n = 25; p < 0.05).
      Despite similar injury indexes in the LAD bed, there was a trend (p = 0.07;
      analysis of variance) toward greater NI/M ratios in the Yucatan minipig versus
      the feeder pig group (1.14 +/- 0.21 vs 0.73 +/- 0.09, n = 7/group). We found no
      such trend in the LCX bed, where the injury index (25.7% +/- 3.5%) was
      significantly greater than that of the LAD (18.2% +/- 1.2%, p < 0.05). If
      variations in balloon-induced vascular injury are accounted for, the technique of
      balloon overinflation of coronary arteries should prove useful in testing
      potential antirestenotic agents in either adult or juvenile pigs.

PMID- 8273741
TI  - Restoration of normal phasic flow velocity after multiple coronary artery stent
      placement.

PMID- 8273742
TI  - Syncope with cardiac arrest as the first manifestation of two congenital left
      coronary artery-to-main pulmonary artery fistulae.

PMID- 8273743
TI  - Postinfarction left ventricular rupture: successful surgical intervention after
      percutaneous cardiopulmonary support during mechanical resuscitation.

PMID- 8273744
TI  - Echocardiographic findings of subepicardial aneurysm of the left ventricle.

PMID- 8273745
TI  - Intermittent masked bifascicular block.

PMID- 8273746
TI  - Presumed single-leaflet mitral valve: recognition by transthoracic and
      transesophageal echocardiography.

PMID- 8273747
TI  - Atrial septal dissection after mitral valve replacement demonstrated by
      transesophageal echocardiography.

PMID- 8273748
TI  - Pulsus alternans as a sign of prosthetic valve dysfunction.

PMID- 8273749
TI  - Variant of Lutembacher's syndrome with intact atrial septum.

PMID- 8273750
TI  - Pulmonary arteriovenous malformations with brain abscess.

PMID- 8273751
TI  - Myocardial dysfunction and necrosis after ingestion of thyroid hormone.

PMID- 8273752
TI  - Innovations in the management of ischemic cardiomyopathy.

PMID- 8273753
TI  - Incremental evaluation of exercise capacity as an independent predictor of
      coronary artery disease presence and extent.
AB  - To determine the independent incremental value of exercise capacity (METS)
      concerning the presence and extent of coronary artery disease, we analyzed data
      from 800 patients with suspected coronary disease who underwent both exercise
      testing and coronary angiography. We performed logistic regression analysis of
      clinical and exercise test data with an incremental design to mimic the usual
      flow of data acquisition. Separate analyses were performed concerning coronary
      disease presence (> or = 1 vessel with a > or = 50% lesion) and extent (three
      vessel/left main disease). Diagnostic accuracy was determined by calculating
      receiver operating characteristic (ROC) curve areas. When considered alone, METS
      was a significant predictor of both presence and extent of disease. Multivariate
      analysis revealed that METS was an independent predictor of disease extent but
      not presence. However, comparison of ROC curve areas failed to show any loss of
      accuracy when METS was removed from the coronary disease extent analysis. Despite
      the strong univariate relationship between exercise capacity and coronary disease
      presence and extent and the independence of exercise capacity as a predictor of
      coronary disease extent, the lack of an additional incremental accuracy
      attributed to its consideration virtually cancels its value as a diagnostic
      variable for assessing both coronary disease presence and extent.

PMID- 8273754
TI  - Influence of right coronary artery stenosis on exercise test responses and
      survival in patients with left main or left main equivalent disease.
AB  - Forty-two patients with angiographically documented left main coronary artery
      (LM) disease (luminal occlusion > or = 50%) and 30 patients with left main
      equivalent (LMEQ) disease (> or = 70% luminal occlusion of both the proximal left
      anterior descending artery and proximal left circumflex artery) were studied to
      determine the role of right coronary artery (RCA) involvement on exercise test
      responses and survival. Significant (> or = 70%) RCA stenosis was present in 30
      (72%) of the 42 LM patients and 16 (53%) of the 30 LMEQ patients. No significant
      differences were observed between LM and LMEQ patients in any clinical or
      exercise variables or survival. Thus both groups were combined for analysis of
      the influence of RCA involvement (i.e., LM/LMEQ with RCA versus LM/LMEQ without
      RCA disease). Greater ischemic responses were observed in the LM/LMEQ group with
      significant stenosis of the RCA. The presence of RCA stenosis was associated with
      significantly greater horizontal or downsloping ST-segment depression during
      exercise (2.4 +/- 1.2 mm vs 1.3 +/- 1.4 mm; p < 0.001), and prolonged recovery
      time until normalization of the ST segment (3.2 +/- 1.4 min vs 2.0 +/- 1.9 min; p
      < 0.01). The LM/LMEQ without RCA disease group behaved like the subgroup with two
      vessel disease, and responses of the LM/LMEQ group with RCA disease were similar
      to the group with three-vessel disease. The annual survival in LM/LMEQ with RCA
      disease was worse than that in LM/LMEQ without RCA disease (average annual
      mortality rates = 7.5% vs 1.0%, respectively; p = 0.05). Infarct-free survival in
      LM/LMEQ with RCA disease was also lower than that in LM/LMEQ without RCA disease.
      Thus although patients with LM and LMEQ were similar in terms of survival and
      exercise responses, the presence of RCA stenosis was associated with
      significantly greater ST-segment depression, a prolonged recovery time until
      normalization of the ST segment, a fivefold increase in the death rate, and
      higher morbidity from myocardial infarction over a 5-year period of follow-up.
      Involvement of the RCA should be considered when making decisions concerning
      medical-surgical management of patients with severe coronary artery disease.

PMID- 8273755
TI  - Right ventricular ejection fraction during exercise in patients with recent
      myocardial infarction: effect of the interventricular septum.
AB  - To investigate the effect of interventricular septum (IVS) on right ventricular
      function during exercise, radionuclide angiocardiography was performed in 50
      patients with recent myocardial infarction. Twenty-five patients had involvement
      of IVS according to thallium uptake in IVS (group I), and 25 patients were free
      of IVS involvement (group II). Although there was no statistical difference
      between the two groups in right ventricular ejection fraction (EF) at rest (45%
      +/- 10% vs 48% +/- 8%), patients in group I had significantly lower left
      ventricular (LV) EF (40% +/- 11% vs 53% +/- 11%, p < 0.01) and larger LV end
      diastolic volume (129 +/- 46 vs 106 +/- 31 ml, p < 0.05) than those in group II.
      All parameters increased significantly during exercise in both groups, but
      patients in group I had significantly lower exercise right ventricular EF (50% +/
      10% vs 56% +/- 9%, p < 0.05), LVEF (44% +/- 11% vs 56% +/- 13%, p < 0.01), and
      larger LV end-diastolic volume (155 +/- 44 vs 129 +/- 37 ml, p < 0.05) than those
      of group II. Significant correlations were observed between right ventricular EF
      and LV end-diastolic volume at rest and during exercise (r = -0.48, p < 0.05, and
      r = -0.68, p < 0.01, respectively) in group I, but right ventricular EF
      correlated with LVEF only at peak exercise (r = 0.65, p < 0.01). In contrast,
      right ventricular EF did not correlate with any variables at rest or during
      exercise in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273756
TI  - Assessment of regional myocardial perfusion with myocardial contrast
      echocardiography in a canine model of varying degrees of coronary stenosis.
AB  - Previous studies showed that myocardial contrast echocardiography can be used to
      detect relative regional underperfusion in a canine model of critical coronary
      stenoses. The aim of this study was to determine if myocardial contrast
      echocardiography performed with a sterile sonicated human serum albumin
      preparation (Albunex, Molecular Biosystems, San Diego, Calif.) could detect the
      presence of coronary stenoses of variable degrees of severity. The results were
      compared with myocardial blood flow as assessed by radiolabeled microspheres in
      16 open-chest dogs during baseline, following the creation of a coronary stenosis
      of variable severity and at the peak of dipyridamole-induced hyperemia. When flow
      ratios (that is, flow in the control area/ischemic area) were examined, a good
      correlation was observed between the area under the time-intensity curve and
      radioactive microsphere blood flow (r = 0.94, p < 0.0001), which allowed
      distinction of mild from severe stenosis. However, a consistent underestimation
      of the dipyridamole-induced hyperemia by myocardial contrast echo was seen in the
      control zone. This could be partially explained by a simultaneous increase in
      coronary blood flow and blood volume with dipyridamole and by attenuation of the
      ultrasound signal because of the high concentration of microbubbles at high
      flows. Myocardial contrast echocardiography can quantitate the amount of
      jeopardized myocardium during various degrees of coronary stenoses.

PMID- 8273757
TI  - Prolonged QT interval in hypertrophic and dilated cardiomyopathy in children.
AB  - When the QT interval is prolonged in a patient with structural heart disease,
      there is a question of whether the QT interval prolongation is the result of
      coexistent long QT interval syndrome or ventricular hypertrophy. The purpose of
      this study was to assess whether QT interval prolongation can be attributed to
      ventricular hypertrophy/dilation alone. Electrocardiograms (ECGs) of 25 children
      in each of six echocardiographically proven groups (right ventricular
      hypertrophy, left ventricular hypertrophy, biventricular hypertrophy,
      hypertrophic cardiomyopathy, dilated cardiomyopathy, and normals) were analyzed.
      All patients had QRS interval durations < 100 msec, and patients with
      ventriculotomies were excluded. No patients in the normal group had a QTc
      interval > or = 0.45 sec. Eight (32%) of 25 patients with dilated cardiomyopathy
      had a QTc interval > or = 0.45 sec (p = 0.007 vs normal), 6 (24%) of 25 patients
      with hypertrophic cardiomyopathy had a QTc interval > or = 0.45 sec (p = 0.03 vs
      normal), and 2 of 25 patients each with right ventricular hypertrophy, left
      ventricular hypertrophy, and biventricular hypertrophy had a QTc interval > or =
      0.45 sec (p = NS vs normal). There was no relation of the QTc interval to age,
      QRS duration, T-wave axis, or heart rate in any group. In the dilated
      cardiomyopathy group, there was no relationship of QTc interval to age,
      shortening fraction, or left ventricular end diastolic dimension. In conclusion,
      (1) a significant number of patients (24% to 32%) with dilated or hypertrophic
      cardiomyopathy may have a long QTc interval on the surface ECG, and (2)
      ventricular hypertrophy/dilation may be additional rare causes of acquired
      prolongation of the QT interval.

PMID- 8273758
TI  - Comparisons of paired orthotopic cardiac transplant donor and recipient
      electrocardiograms.
AB  - Electrocardiograms of 20 consecutive donor and paired recipient orthotopic heart
      transplant patients were compared. Recipients were markedly older than donors;
      all patients were males, and both groups had similar body weight. The heart rate
      was faster, QRS was longer, QT was shorter, QRS axis was more shift to the left,
      and precordial voltage was decreased in the recipient ECGs in the first 72 hours
      after transplant. These changes persisted during late follow-up (12 +/- 6 months
      after transplant). Seventy percent and 60% of recipients within the first 72
      hours after transplant and during late follow-up, respectively, had a new RBBB
      delay compared to their paired donor ECG. There was a trend toward less clockwise
      rotation in the ECGs of patients who had a new incomplete RBBB in the late follow
      up compared to patients who did not. Thus new RBBB delays, QT shortening, QRS
      axis left shift, and decrease in precordial voltage are commonly seen on ECGs
      after orthotopic cardiac transplantation. A new heart position and recipient's
      weight do not seem to account for the development of a new RBBB delay and
      decrease in precordial voltage. Other factors, such as mechanical or thermal
      injury and change in donor-to-recipient age, may be involved.

PMID- 8273759
TI  - Risk and benefit of additional aortocoronary bypass grafting in patients
      undergoing cardioverter-defibrillator implantation.
AB  - It is unclear whether additional aortocoronary bypass grafting should be
      performed in patients who need an automatic implantable cardioverter
      defibrillator (ICD) in one- or two-step procedures. Therefore we studied the
      follow-up of 139 patients who underwent epicardial implantation of the
      cardioverter defibrillator (CD). All patients had coronary artery disease and
      recurrent ventricular tachycardia or fibrillation. Eighty-nine patients had
      implantation of the CD without additional surgical approaches (group G1), and 50
      patients had concomitant aortocoronary bypass grafting (group G2). Perioperative
      mortality (within 30 days after CD implant) was 1 (1%) of 89 patients in G1 and 6
      (12%) of 50 patients in G2 (p < 0.01). During the mean follow-up of 26 +/- 20
      months, sudden death occurred in four (4%) of 89 patients in G1 and two (4%) of
      50 patients in G2. Twenty-three (17%) patients died of cardiac failure (18 [20%]
      patients in G1 and 5 [10%] patients in G2). ICD discharges occurred in 69 (78%)
      of 89 patients in G1 and in 36 (72%) of 50 patients in G2. The mean incidence of
      ICD discharges was 23 +/- 69 shocks per patient in G1 and 18 +/- 25 shocks per
      patient in G2 (p = NS). We conclude that concomitant aortocoronary bypass
      grafting during CD implantation leads to a higher perioperative mortality.
      Avoidance of myocardial ischemia does not significantly influence sudden death
      mortality nor markedly reduce the number of ICD discharges.

PMID- 8273760
TI  - Angiographic follow-up after successful percutaneous coronary angioplasty for
      chronic total coronary occlusion: experience in 110 consecutive patients.
AB  - Percutaneous transluminal coronary angioplasty (PTCA) was performed in 110
      consecutive patients (111 vessels) with chronically occluded coronary arteries
      and was successful in 69 patients (69 vessels). Successful initial PTCA was
      related to the extent of coronary artery disease, the morphology of the proximal
      surface of the occlusion site, and the clinical duration of occlusion. Repeat
      angiography was performed for 62 patients, with successful initial PTCA and
      demonstrated restenosis in 34 (55%) patients, of whom 11 had total occlusion.
      Repeat PTCA was performed in 30 patients and was successful in 80%. Follow-up
      angiography after repeat PTCA was carried out in all patients who underwent
      successful second PTCA, and, it demonstrated re-restenosis in 7 (29%) patients.
      In this study, among 111 total occlusions, 28 vessels undergoing successful
      initial PTCA and 17 undergoing successful repeat PTCA were free from restenosis
      or re-restenosis at the time of follow-up angiography.

PMID- 8273761
TI  - Double loop figure-of-8 reentry as the mechanism of multiple atrioventricular
      node reentry tachycardias.
AB  - Seven patients with multiple atrioventricular node reentry tachycardia were
      analyzed to unravel the mechanism of these tachycardias. Six of the seven
      patients showed anterograde dual atrioventricular node pathways and one showed
      anterograde conduction through the fast pathway. Three types of retrograde
      pathways were noted among these seven patients: (1) the fast pathway with the
      earliest atrial activation at the His bundle area; (2) the intermediate pathway
      with the earliest atrial activation at the ostium of the coronary sinus; and (3)
      the slow pathway with the earliest atrial activation at the ostium of the
      coronary sinus. All seven patients used the intermediate pathway for retrograde
      conduction. However, one patient showed evidence of retrograde slow pathway
      conduction with demonstrable retrograde dual pathways, and another showed
      evidence of retrograde fast pathway conduction with a shift of atrial activation
      sequence when conduction switched to the intermediate pathway. Four different
      types of reentry circuits using either the fast or the slow pathway as the
      anterograde limb and one of the three retrograde pathways as the retrograde limb
      were demonstrated in these seven patients, resulting in two types of tachycardias
      in four patients and three types of tachycardias in three patients. A change in
      tachycardia type could be induced with atrial or ventricular stimulation. A
      radiofrequency current delivered to the inferior aspect of Koch's triangle along
      the tricuspid anulus in five patients resulted in selective ablation or
      modification of the intermediate pathway or the slow pathway, with preservation
      of anterograde atrioventricular conduction and abolition of tachycardias. The
      findings suggest that a double loop figure-of-8 reentry circuit including a fast
      pathway, a slow pathway, and an intermediate pathway is responsible for multiple
      atrioventricular node reentry tachycardias.

PMID- 8273762
TI  - Acquired immunodeficiency syndrome in the United States associated with injecting
      drug use, 1981-1991.
AB  - As of June 30, 1991, 182,834 AIDS cases in the United States had been reported to
      the Centers for Disease Control, of which 58,879 (32.2%) were associated with
      illicit drug use. Of these, 39,904 (70.0%) were in both women and heterosexual
      men reported as injecting drug users (IDUs), 11,823 (20.7%) in men who have sex
      with men who are also IDUs, 5,305 (9.3%) in sex partners of IDUs, and 1,847
      (3.1%) in children whose mothers were either IDUs or sex partners of IDUs. From
      1989 to 1990, the increase in the number of United States AIDS cases associated
      with IDU either directly or indirectly was higher in all regions compared with
      the Northeast. The highest percentage increases were in the South, U.S.
      territories, and the North Central. From 1989 to 1990, the percentage of AIDS
      cases attributed directly to IDU increased in women and men (15.3 and 5.9%,
      respectively); however, the increase in sex partners of IDUs was much larger
      (34.5% in men and 29.1% in women). Increases were also higher in sex partners of
      IDUs than in IDUs when compared by race/ethnicity and by region of residence.
      Because HIV can spread rapidly among IDUs and their sex partners, there is an
      immediate need for targeting effective HIV prevention messages to all IDUs and
      their sex partners in communities with high HIV infection rates.

PMID- 8273763
TI  - Predictors of changes in sexual behavior among women on methadone.
AB  - This study identified predictors of reported sexual risk reduction among 109
      female injection drug users enrolled in methadone clinics. Univariate analyses
      were used to examine the individual effects of each variable on the outcome of
      sexual behavior change over the past 6 months. Multiple logistic regression was
      then used to identify which of these variables were independently associated with
      such a change. Women with more than one sexual partner were more likely than
      women with one or no sexual partner to report changing their sexual behavior.
      African-American women were less likely than White Anglo or Latina women to
      report changing their sexual behavior. Women who held stronger beliefs that luck
      plays the largest role in getting AIDS were less likely to report changing their
      sexual behavior. Change in sexual behavior was associated with feeling
      comfortable asking partners to use condoms, higher depression scores, and loss of
      friends or family to AIDS. The observed relationship between personal
      susceptibility and depression suggests that risk reduction interventions should
      also address the depressive symptomatology associated with feelings of
      vulnerability.

PMID- 8273764
TI  - Self-reported drug use data: what do they reveal?
AB  - The purpose of this study is to examine self-reported marijuana and cocaine use
      responses from two nationally representative surveys. We compared prevalence
      rates across birth cohorts for multiple years of the National Household Survey of
      Drug Abuse (NHSDA) and also analyzed longitudinal inconsistencies in self
      reported drug use between two waves of the National Longitudinal Survey Youth
      Cohort (NLS-Y). We found the percentages of respondents admitting use within the
      past month, year, and lifetime were comparable to other findings and were
      consistent with the declining trend in drug use in the late 1980s. A comparison
      of lifetime prevalence rates revealed seemingly inconsistent reports between 1985
      respondents and their birth cohorts in 1990. Using the longitudinal NLS-Y data,
      we found that roughly one-fifth of the people who had admitted using marijuana or
      cocaine in their lifetime on the 1984 survey subsequently denied ever having used
      in 1988. The majority of these cases were people who reported having used
      infrequently. The subsample of women had similar patterns. In addition, we
      discovered that women who had been pregnant between the two surveys were more
      likely to inconsistently deny having ever used, while those who were currently
      pregnant responded more honestly about their past use. Overall, we found that
      although most people are willing to provide accurate accounts of their use, the
      researcher should be aware that under-reporting or complete denial does occur.
      Most importantly, external factors appear to contribute to the rate of inaccurate
      reporting.

PMID- 8273765
TI  - Reported prevalence of drug abuse comorbidity in a city-wide emergency rooms
      system.
AB  - Frequency and results of urine toxicology screens in a state-guided system of
      emergency rooms in a large city were compared with frequency and results of the
      same tests in the same population at a university-run intensive treatment
      psychiatric unit. Differences both in prevalence and in results were noted, with
      the emergency rooms testing significantly less patients than the intensive
      treatment unit and documenting a significantly lower rate of active substance
      abuse comorbidity to psychiatric disorders. Possible explanations for these
      differences are discussed, including clinical, attitudinal, and cost containment
      factors. These findings have a definite impact on treatment decision making,
      diagnostic precision, and validity of epidemiologic reports.

PMID- 8273766
TI  - Effects of acute buprenorphine on responses to intranasal cocaine: a pilot study.
AB  - Five inpatients dependent on both intravenous cocaine and heroin were detoxified
      from opiates. They were then given 5 days of double-blind treatment with active
      or placebo buprenorphine 2 mg/d sublingually, followed by a crossover to the
      converse for 5 days (buprenorphine or placebo). Intranasal cocaine challenges (2
      mg/kg) were performed on Days 3 and 5 of each treatment. Buprenorphine
      significantly enhanced patients' ratings of cocaine-induced pleasurable effects,
      and augmented cocaine-induced pulse increases. The buprenorphine enhancement of
      subjective cocaine effects appeared to be more prominent on Day 3 than on Day 5.
      This reduction from Day 3 to Day 5 suggests that cocaine may interact differently
      with buprenorphine as treatment is more prolonged.

PMID- 8273768
TI  - Attributional style in children of substance abusers.
AB  - This study examined attributional style in children of substance abusers. We
      hypothesized that children of substance abusers are more likely to develop a
      depressogenic attributional style. Forty children between the ages of 8 and 14
      participated in the study. Twenty children were from families with a history of
      substance abuse and 20 were from families without such a history. Each child
      completed self-report measures of depression and attributional style. After
      controlling for depression and other factors, the results revealed that children
      of substance abusers had a more depressogenic attributional style than did
      children without such a family history. Implications of the results for children
      of substance abusers and for hopelessness theory are discussed.

PMID- 8273767
TI  - Do methadone patients substitute other drugs for heroin? Predicting substance use
      at 1-year follow-up.
AB  - Data were analyzed from the nationwide Treatment Outcome Prospective Study (TOPS)
      to assess whether current and former methadone patients substitute other drugs
      for heroin. The sample comprised 513 heroin users who were admitted to methadone
      programs in 10 cities across the United States and followed for at least 1 year.
      Structured face-to-face interviews were administered at admission and at follow
      up to assess use of six substances: cocaine, amphetamines, illegal methadone,
      tranquilizers, marijuana, and alcohol. The study found a decline in the use of
      all substances except alcohol. Patients who substantially reduced or eliminated
      their use of heroin during the follow-up year were more likely to decrease their
      use of other drugs than were patients who continued to use heroin on a weekly or
      more frequent basis. These findings suggest that methadone programs indirectly
      reduce patients' use of cocaine, amphetamines, illegal methadone, tranquilizers,
      and marijuana, insofar as they are successful in eliminating or decreasing heroin
      use. Similar reductions in drug use were found among patients who were not
      enrolled in methadone programs during the follow-up year. These findings do not
      support the commonly held belief that heroin addicts substitute other drugs for
      heroin.

PMID- 8273769
TI  - Substance abuse in borderline personality disorder.
AB  - The impact of substance abuse on patients with borderline personality disorder
      was investigated. Substance abuse was common. Female patients preferred alcohol
      and sedatives. Male patients preferred stimulants. Substance abuse was associated
      with poor school performance, unemployment, and promiscuity. Depersonalization
      derealization was common in nonsubstance using and alcohol-sedative using
      patients, but was rarely found in stimulant users. Substance abuse appears to be
      a devastating complication in the patient with borderline personality disorder.

PMID- 8273770
TI  - Rational recovery: alternative to AA for addiction?
AB  - Rational Recovery (RR) is a new self-help movement for substance abusers, with a
      cognitive orientation. It has been suggested as an alternative to Alcoholics
      Anonymous. This study was designed to examine the nature of RR and its impact on
      those who join. A national sample of 433 substance-abusing people attending 63
      established RR groups was evaluated, using codable self-report questionnaires
      completed at RR meetings. Members were mostly men with college experience who had
      previously attended AA. Among recruits who attended their first RR meeting in the
      last month, 38% were abstinent in the last month. Among members who had joined 3
      or more months before, 73% were abstinent in the last month; they had attended an
      average of 4.1 RR meetings in that month, and carried out exercises at home based
      on Rational Emotive Therapy. Among those who joined 6 or more months before, 58%
      reported at least 6 months of abstinence. Among members with a history of heavy
      cocaine use, the portion reporting abstinence in the last month was not
      significantly different from those who had never used cocaine. The minority of
      members who were engaged for 3 months were still drinking, though, and did so on
      an average of 9.9 days in the last month. RR succeeded in engaging substance
      abusers and promoting abstinence among many of them while presenting a cognitive
      orientation that is different from the spiritual one of AA. Its utility in
      substance abuse treatment warrants further assessment.

PMID- 8273771
TI  - Patterns of polydrug use in adolescent alcohol abusers.
AB  - It is clear that alcohol abuse by adolescents rarely exists today without the
      concurrent use of other drugs. Little is known, however, about the extent and
      patterns of polydrug use in clinical samples of adolescent alcohol abusers. The
      present study examined patterns and correlates of polydrug use in 72 adolescents
      admitted to an inpatient treatment unit with a diagnosis of alcohol abuse. The
      degree of lifetime involvement with 10 different drug classes was assessed in a
      clinical interview. Ninety-six percent of subjects reported use of drugs other
      than alcohol, and there were substantial rates of use for most drug classes.
      Males and females did not differ in the percentage of subjects who used different
      drug classes or in severity of involvement ratings for these drug classes. The
      data suggest a consistent ordering of drug classes, such that the use of drug
      classes later in this order was rare in the absence of the use of drug classes
      earlier in the order. The data suggest that polydrug use characterizes the large
      majority of adolescent alcohol abusers, and that such use is often quite
      extensive. Implications for assessment and treatment are discussed.

PMID- 8273772
TI  - Regional differences in alcohol consumption and drinkers' attitudes toward
      drinking.
AB  - Based on a November 1986 national probability sample of American adults aged 21
      and over (1,069 of whom were deemed "drinkers" on the basis of having consumed at
      least one alcoholic beverage in the 7 days prior to interview), this study
      examines whether region of residence influences drinkers' alcohol consumption
      and/or their perceptions of alcohol use. In addition to examining the main
      effects of the relationship between geographic region of residence and alcohol
      use, four measures of urbanization are also investigated for their influence on
      drinking. Results indicate that geographic region of residence makes little to no
      difference in people's alcohol use and has only a small impact on their drinking
      related attitudes. By and large, urbanization and gender are not influential
      variables in these relationships.

PMID- 8273773
TI  - Understanding the pathophysiology of dysphagia and constipation in neurologic
      disorders.

PMID- 8273774
TI  - Immunohistochemical expression of carbohydrate antigen 19-9 in colorectal
      carcinoma.
AB  - OBJECTIVES: Carbohydrate antigen 19-9 (CA19-9) is one of the most representative
      tumor markers in colorectal carcinomas. We studied the immunohistochemical
      expression of CA19-9 in primary colorectal carcinoma to identify its significance
      as a prognostic factor. METHODS: The avidin-biotin-peroxidase complex method was
      used for CA19-9 staining in sections from 149 patients with primary colorectal
      carcinoma. The data were studied by univariate and multivariate analyses.
      RESULTS: 86 tumors (56%) stained positively. The staining pattern was classified
      into three groups: group I (a stromal type, 22 tumors), group II (an apical
      and/or cytoplasmic type, 64 tumors), and group III (no staining, 63 tumors).
      Eight clinicopathologic variables showed a significant relationship with the
      staining pattern of CA19-9. The 5-yr survival rate of the group I subjects was
      significantly lower than that of the other two groups. With the multivariate
      analysis, the staining pattern of CA19-9 proved to be one of the independent
      prognostic variables. CONCLUSIONS: In addition to conventional prognostic
      factors, the staining pattern of CA19-9 is considered to be of value in
      predicting the prognosis of patients with colorectal carcinomas.

PMID- 8273775
TI  - Idiopathic autoimmune chronic hepatitis triggered by hepatitis A.
AB  - Hepatitis A virus (HAV) infection is a well-recognized cause of acute hepatitis
      with jaundice in adults. However, chronic sequelae of HAV infection are so rare
      and so poorly defined that their existence remains speculative. In this report we
      describe a middle-aged woman in whom serologically defined acute hepatitis A
      appeared to trigger the onset of autoimmune chronic active hepatitis. This and
      two previously reported cases suggest that in certain individuals, presumably
      with a genetic predisposition to the development of autoimmune hepatitis, HAV
      infection may be the precipitating event in the pathogenesis of this disorder.

PMID- 8273776
TI  - Performance of ERCP for symptomatic choledocholithiasis during pregnancy:
      techniques to increase safety and improve patient management.

PMID- 8273777
TI  - Atypical presentation of Crohn's disease: severe, recurrent iron deficiency
      anemia dependent on blood transfusions.
AB  - We report an unusual case of Crohn's disease. Our subject, a 43-yr-old lady,
      presented with severe iron deficiency anemia, hypoproteinemia and
      lymphocytopenia, but without any clinical manifestations of Crohn's disease
      either at presentation or during follow-up. She had recurrent episodes of severe
      iron deficiency anemia, repeatedly requiring blood transfusions (28 units in 20
      months). She was found to have a short stricture with ulceration in the ileum due
      to Crohn's disease, and a blind loop with bacterial overgrowth above it.
      Resection of the affected area prevented further recurrence of anemia and
      corrected hypoproteinemia. We postulate that her anemia and hypoproteinemia were
      due to blood and protein (lymph) loss from the ulcerated area in the ileum. Such
      a presentation has not been described before.

PMID- 8273778
TI  - Superior mesenteric venous thrombosis masquerading as Crohn's disease.
AB  - Superior mesenteric venous (SMV) thrombosis is an uncommon cause of mesenteric
      ischemia, frequently presenting with nonspecific and subacute symptoms. We report
      a case of a 28-yr-old man presenting with symptoms and radiographic changes
      suggestive of Crohn's disease who, upon further evaluation, was found to have SMV
      thrombosis. A search for a precipitating condition revealed a strong family
      history of thromboembolic disease and deficiency of protein C. The patient
      responded to supportive therapy and anticoagulation.

PMID- 8273779
TI  - Adenocarcinoma in strictures of ulcerative colitis without antecedent dysplasia
      by colonoscopy.
AB  - We report three patients with chronic ulcerative colitis and colonic strictures
      that were found to harbor advanced adenocarcinomas despite previous endoscopic
      examinations that had failed to demonstrate dysplasia or carcinoma. This
      experience calls into question the reliability of endoscopic monitoring of the
      subset of ulcerative colitis patients with strictures. Review of the literature
      supports the thesis that the management of these patients requires a high index
      of suspicion of malignancy, and should include timely consideration of surgery.
      It is suggested that evaluation of the effectiveness of endoscopic surveillance
      programs for patients with ulcerative colitis should consider the subset of
      patients with strictures as a separate cohort.

PMID- 8273780
TI  - Multiple large hyperplastic polyps of the colon coincident with adenocarcinoma.
AB  - Diminutive hyperplastic polyps are the most common non-neoplastic lesions of the
      colon. Typically, they are small (< 0.5 cm) sessile lesions, lack cellular
      atypia, and are found predominantly in the rectosigmoid region of the colon.
      Multiple large hyperplastic polyps (> 1 cm) are rare. Although the relationship
      between diminutive hyperplastic polyps and adenomatous polyps or carcinoma is
      controversial, even less data are available on the significance of large
      hyperplastic polyps. We report the case of a 56-yr-old man who was seen because
      of fatigue, anemia, and Hemoccult-positive stool. On air contrast barium enema
      study and colonoscopy, multiple polyps that were similar in appearance were found
      distributed symmetrically throughout the colon. However, histologic examination
      revealed 16 hyperplastic polyps 1-2 cm in size, multiple diminutive hyperplastic
      polyps, one adenomatous polyp, and one adenomatous polyp containing well
      differentiated adenocarcinoma. Because multiple large hyperplastic polyps are
      rare, we suspect this entity may be distinct from diminutive hyperplastic polyps.
      In our patient, large hyperplastic polyps were distributed symmetrically
      throughout the colon and were associated with a synchronous carcinoma. Because
      large hyperplastic polyps may be coincident with adenomatous polyps and carcinoma
      of the colon, we recommend that patients found to have large hyperplastic polyps
      undergo removal of all polyps for histologic study.

PMID- 8273781
TI  - The endoscopic diagnosis of the invaginating ampulla of Vater mimicking
      choledocholithiasis.

PMID- 8273782
TI  - Angioedema of the small bowel caused by an angiotensin-converting enzyme
      inhibitor.

PMID- 8273783
TI  - Polycystic liver disease mimicking sclerosing cholangitis during endoscopic
      retrograde cholangiopancreatography.

PMID- 8273784
TI  - Gastrointestinal histoplasmosis in HIV infection: two cases of colonic
      pseudocancer and review of the literature.
AB  - Primary gastrointestinal infection is an uncommon manifestation of
      histoplasmosis. It is almost always associated with disseminated disease and/or
      an immunocompromised host. The ileum and cecum are the most common sites
      involved. We report two cases of primary gastrointestinal histoplasmosis in HIV
      seropositive men who presented with annular constricting right colon lesions.

PMID- 8273785
TI  - Neoplastic seeding as a complication of percutaneous endoscopic gastrostomy.

PMID- 8273786
TI  - Massive lower gastrointestinal hemorrhage in an AIDS patient: first case report
      of ulcerated lymphoma in a Meckel's diverticulum.

PMID- 8273787
TI  - A good defense, doc?

PMID- 8273788
TI  - Response to editorial by Chobanian et al., and article by Fitzgibbons.

PMID- 8273789
TI  - Re: Endoscopic stent treatment of the sump syndrome.

PMID- 8273790
TI  - Helicobacter pylori infection in infants born from positive mothers.

PMID- 8273791
TI  - Pyrogenic liver abscess following infection of a ventriculoperitoneal shunt.

PMID- 8273792
TI  - Characterization of swallowing and defecation in Parkinson's disease.
AB  - Despite the high prevalence of Parkinson's disease, the pathophysiology of its
      gastrointestinal symptoms remains poorly understood. OBJECTIVES: to evaluate
      swallowing and defecatory function in patients with Parkinson's disease and age-
      and sex-matched controls and to correlate objective findings with subjective
      symptoms. METHODS: The following studies were performed on 13 patients with
      Parkinson's disease and seven controls: extrapyramidal function assessment,
      gastrointestinal symptom survey, videoesophagram, colon transit study,
      defecography, and anorectal manometry. RESULTS: Abnormal salivation (frequency,
      %, control vs. Parkinson's disease: 14 vs. 77, p < 0.05), dysphagia (14 vs. 77, p
      < 0.05), constipation (14 vs. 31, p < 0.05), and defecatory dysfunction (29 vs.
      77, p < 0.05) were more common among Parkinsonian patients. However,
      videoesophagographic abnormalities were equally common in both groups. Colon
      transit time was significantly prolonged in the Parkinson's disease group.
      Altered puborectalis function was noted on defecography in 31% of Parkinson's
      disease subjects, but in none of the controls (p < 0.05). Anorectal manometry
      identified several abnormalities in the Parkinson's disease group, which included
      decreased basal anal sphincter pressures, prominent phasic fluctuations on
      squeeze, and a hyper-contractile external sphincter response to the
      rectosphincteric reflex. Many patients exhibited both slow transit and manometric
      abnormalities, and symptoms were poor predictors of test results. CONCLUSION: In
      this group of patients with mild to moderate Parkinson's disease,
      videoesophagographic abnormalities were not confined to the patients with
      Parkinson's disease. Studies of colonic and anorectal function, in contrast,
      identified a number of abnormalities. Therefore, colonic and anorectal
      dysfunction appears to be an early gastrointestinal manifestation of Parkinson's
      disease, and may represent the direct involvement of the gut by this disease
      process.

PMID- 8273793
TI  - Five-year maintenance treatment with ranitidine: effects on the natural history
      of duodenal ulcer disease.
AB  - In this study, we assessed the effect of a 5-yr maintenance program with
      ranitidine on the natural history of duodenal ulcer disease both during treatment
      and after drug withdrawal. Two groups of patients with duodenal ulcer were
      studied. In group A patients (n = 40), ranitidine (150 mg/day) was given
      continuously for 5 yr; group B patients (n = 40), received seasonal, 8-wk
      prophylactic treatment with ranitidine (300 mg/day), in spring and fall. Routine
      endoscopy was performed every year and whenever ulcer symptoms recurred. After
      the 5-yr study, the drug was discontinued in both groups, and patients underwent
      endoscopy after 3, 6, 12, and 18 months. The probability of duodenal ulcer
      recurrence was significantly lower in patients continuously receiving ranitidine
      (p < 0.001), and ulcer complications were significantly lesser in group A
      patients (p < 0.03). In the 18 months of follow-up after drug discontinuation,
      only 15% (4/26) of patients of group A relapsed, whereas ulcer recurrence was
      diagnosed in 84% (26/32) of group B patients (p < 0.001). We conclude that low
      dose continuous treatment with ranitidine is preferable to seasonal prophylaxis
      for its ability to modify the natural history of duodenal ulcer disease.

PMID- 8273794
TI  - Use of high efficacy, lower dose triple therapy to reduce side effects of
      eradicating Helicobacter pylori.
AB  - OBJECTIVES: To evaluate two triple-therapy (TT) regimens of colloidal bismuth
      subcitrate (CBS), metronidazole, and tetracycline HCl in eradicating Helicobacter
      pylori, with particular attention to the frequency of resulting adverse effects
      of the two therapies. METHODS: A prospective, randomized controlled trial was
      conducted in patients with symptoms of dyspepsia who were positive for H. pylori.
      Subjects received a 14-day course of either 4 x/day therapy of CBS (108 mg),
      tetracycline HCl (500 mg), and metronidazole (250 mg), or 5 x/day therapy of CBS
      (108 mg), tetracycline HCl (250 mg), and metronidazole (200 mg). H. pylori status
      was determined endoscopically by urease test, histology, and culture. Standard
      questionnaires were administered to determine compliance to treatment and side
      effects of therapy. RESULTS: H. pylori was eradicated in 196/213 (92%) patients
      in the 4 x/day group and 202/210 (96%) in the 5 x/day group (p = 0.07). Side
      effects were significantly less frequent and less severe in the 5 x/day group (p
      < 0.01). CONCLUSIONS: We conclude that a lower dose, 5 x/day triple therapy
      treatment of H. pylori is equally efficacious to the standard 4 x/day therapy,
      but is accompanied by fewer and milder adverse effects.

PMID- 8273795
TI  - Medium-term results of oral and intravenous omeprazole/amoxicillin Helicobacter
      pylori eradication therapy.
AB  - OBJECTIVES: The aim of the present study was to examine the effect of the
      application route of the antibiotic amoxicillin in Helicobacter pylori
      eradication, using omeprazole/amoxicillin. METHODS: In a prospective medium-term
      study, 31 patients with H. pylori-positive gastroduodenal ulcer disease were
      treated with a 14-day course of 20 mg omeprazole bid orally, combined with either
      1 g amoxicillin tid intravenously (n = 15) or 500 mg amoxicillin six times daily
      orally (n = 16). RESULTS: H. pylori eradication, defined as negative bacterial
      findings in urease test, culture, and histology at least 4 wk after cessation of
      study medication, was achieved in 93% (14/15) of the patients in the first group
      and in 91% (11/12) of the patients in the second group. To obtain medium-term
      results, patients in whom H. pylori had been successfully eradicated were
      investigated with a 13C-urea breath test at least 6 months later. Medium-term
      eradication rates of 91% (10/11 patients) in the first and 100% (10/10 patients)
      in the second group were observed. CONCLUSIONS: In view of the equally high
      eradication rates obtained by a 14-day course of intravenously administered
      amoxicillin and an oral therapy of the same length and dosage, during the
      necessary induction of luminal hypoacidity by the proton pump inhibitor
      omeprazole, we conclude that the route of administration of amoxicillin does not
      play a decisive role in bacterial eradication.

PMID- 8273796
TI  - Intravenous tobramycin and metronidazole as an adjunct to corticosteroids in
      acute, severe ulcerative colitis.
AB  - OBJECTIVES: The aim of this study was to evaluate the role of metronidazole and
      tobramycin as an adjunct to corticosteroids in acute, severe ulcerative colitis.
      METHODS: Thirty-nine consecutive patients with severe ulcerative colitis were
      randomized on admission to the hospital to receive intravenously either
      metronidazole (0.5g tid) and tobramycin (4 mg/kg tid) (n = 19), or placebo (n =
      20). In addition, they were given parenteral nutrition, intravenous
      hydrocortisone (100 mg qid) and hydrocortisone enemas (100 mg bid). All patients
      were assessed after 10 days of continuous treatment, or at any time a severe
      complication occurred. RESULTS: Twelve of 19 patients (63.15%) treated with
      antibiotics and 13/20 patients (65%) with placebo showed substantial improvement.
      Seven patients in each group did not improve (n = 9), or developed complications
      (n = 5) and underwent emergency colectomy without perioperative deaths or late
      deaths. CONCLUSIONS: These results do not support the routine use of intravenous
      tobramycin and metronidazole in the treatment of severe ulcerative colitis.

PMID- 8273797
TI  - Hepatic osteodystrophy in primary biliary cirrhosis: effects of medical
      treatment.
AB  - OBJECTIVES: Osteoporosis is a frequent extrahepatic complication of primary
      biliary cirrhosis. Although histologically similar to the osteoporosis commonly
      seen in postmenopausal females, the pathogenesis and management of bone disease
      in patients with primary biliary cirrhosis is poorly understood. The experience
      with a subgroup of patients with primary biliary cirrhosis treated with vitamin
      D, calcium, and estrogen supplementation was reviewed to determine the effects of
      medical treatment on hepatic osteodystrophy. METHODS: The records of 203 women
      with the diagnosis of primary biliary cirrhosis were reviewed retrospectively for
      lumbar spine bone mineral density, menopausal status, and supplementation with
      vitamin D, calcium, and estrogen. RESULTS: The 16 postmenopausal patients treated
      with estrogen replacement had a statistically significant increase in the lumbar
      spine bone mineral density at 1 yr (+0.014 +/- 0.049 vs. -0.03 +/- 0.046 g/cm2, p
      < 0.038), without a significant change in the serum bilirubin or alkaline
      phosphatase. In treated patients, vitamin D and calcium supplementation did not
      lead to significant improvement in lumbar spine bone mineral density.
      CONCLUSIONS: Calcium and vitamin D supplementation, even in the presence of
      vitamin D deficiency, do not improve lumbar spine bone mineral density in
      patients with primary biliary cirrhosis. Estrogen replacement in postmenopausal
      patients, however, does appear to improve lumbar spine bone mineral density
      without increasing clinical or biochemical cholestasis, a potential complication
      reported in animal studies. This study should serve as an impetus for a
      controlled trial of estrogen replacement in postmenopausal patients with primary
      biliary cirrhosis.

PMID- 8273798
TI  - Diagnosis of colon cancer by lavage cytology with an orally administered balanced
      electrolyte solution.
AB  - OBJECTIVE: We wished to evaluate the feasibility of colon lavage cytology using
      an orally administered balanced electrolyte solution. METHODS: Thirty-three
      patients undergoing colonoscopy for suspected colorectal cancer were entered into
      the study. Fifteen of these patients eventually had pathological confirmation of
      colorectal cancer, and one patient had prostatic adenocarcinoma with invasion of
      the rectum. The other 17 patients had no colonoscopic evidence of neoplasm and
      therefore served as controls. Prior to colonoscopy, patients received 10 mg of
      bisacodyl by mouth and enough Colyte to produce a clear anal effluent for
      cytological examination. The colon lavage cytology was interpreted by a
      cytopathologist blinded to the clinical features of each case. RESULTS: In 14 of
      15 (93%) cases of biopsy proven colorectal cancer, the lavage cytology was
      positive: 10 cases demonstrated adenocarcinoma cells and four cases showed
      dysplastic cells. In contrast, the cytology was negative for dysplastic or
      malignant cells in the control patients. CONCLUSIONS: Colon lavage cytology using
      an orally administered balanced electrolyte solution provides acceptable
      specimens for cytological evaluation and had a 93% sensitivity and 100%
      specificity in our population.

PMID- 8273799
TI  - Non-A, non-B fulminant hepatitis is also non-E and non-C.
AB  - OBJECTIVES: to define the roles of the hepatitis C and E viruses (HCV and HEV) in
      non-A, non-B (NANB) fulminant hepatitis. METHODS: we utilized the polymerase
      chain reaction to amplify HCV and HEV RNA sequences and assays to detect
      antibodies to HCV and HEV in the acute phase sera of eight presumed viral NANB
      and seven nonviral NANB fulminant hepatic failure (FHF) patients. RESULTS: none
      of the 15 patients had detectable HCV or HEV RNA or elevated HCV and IgM-HEV
      antibody titers in their acute phase sera. Three patients, all with features of
      autoimmune hepatitis, had raised IgG-HEV antibody titers. Due to the possibility
      of serologically undetectable hepatitis B virus (HBV) infection in fulminant
      hepatitis patients, we performed polymerase chain reaction amplification of HBV
      genomic DNA in acute phase sera of the presumed viral NANB FHF patients and
      subsequently found no evidence of HBV DNA. CONCLUSIONS: we did not find evidence
      implicating HCV or HEV in presumed viral NANB FHF or as agents contributing to or
      causing the liver failure in nonviral NANB FHF patients with autoimmune
      hepatitis, drug-induced hepatotoxicity, or halothane hepatotoxicity.

PMID- 8273800
TI  - The "institutional colon": a frequent colonic dysmotility in psychiatric and
      neurologic disease.
AB  - OBJECTIVES: The true existence of a disease entity termed "institutional colon"
      has remained controversial. The present study serves to test whether this entity
      actually exists and how frequently psychiatric and neurologic diseases are
      associated with colonic dysmotility. METHODS: Using the hospital discharge
      records of four million US military veterans, we investigated the comorbid
      occurrence of volvulus, impaction of intestine, constipation, and megacolon with
      any neurologic or psychiatric disease. RESULTS: Comorbidity of colonic and
      neurologic/psychiatric diseases in identical subjects occurred two to three times
      more often than one would expect from the overall distribution of each group of
      diseases alone. Presenile dementia and Alzheimer's disease, Parkinson's disease,
      multiple sclerosis, and quadriplegia were associated significantly with all four
      colonic diseases. The various forms of schizophrenia coincided mostly with
      megacolon and constipation. Major depressive disorder was associated only with
      constipation, but with none of the other colonic diseases. CONCLUSION:
      Psychiatric and neurologic diseases are frequently associated with colonic
      dysmotility. The association raises the possibility of a pathophysiologic link
      involving the neuronal control of colonic motility.

PMID- 8273801
TI  - Effect of cigarette smoking on gallbladder emptying and filling in man.
AB  - OBJECTIVE: The effect of cigarette smoking on gallbladder (GB) emptying and
      refilling after a fatty meal was examined in 10 healthy volunteers (four women
      and six men, mean age 27.6 yr). METHODS: On three different days, the subjects
      underwent in randomized order: a control test without smoking (C), or they smoked
      two cigarettes during the early (0-20 min; S0-20), or late (20-40 min; S20-40)
      phase of the meal-induced GB emptying. GB volumes were measured
      ultrasonographically before the meal and at 10, 20, 30, 40, 60, 90, 120, 150, and
      180 min postprandially. Two-way ANOVA was applied for statistical assessment of
      the results. RESULTS: The fasted GB volumes amounted to 15.7 +/- 1.8 cm3 (C),
      15.0 +/- 1.7 cm3 (S0-20), and 18.4 +/- 2.3 cm3 (S20-40), F2;18 = 1.524, NS.
      Maximum GB emptying was observed until 60 min after the meal, with a nadir of the
      GB volume amounting to 7.3 +/- 1.3 cm3 (C), 6.6 +/- 1.2 cm3 (S0-20), and 7.1 +/-
      1.1 cm3 (S20-40). No significant difference was found between the stimuli tested
      when absolute GB volumes were considered: F2;180 = 2.725, NS. Analysis of the GB
      emptying-refilling curves normalized for the fasted GB volume revealed that a
      significant inhibitory effect was produced by smoking two cigarettes during the
      late phase of GB emptying on the subsequent GB refilling: F2;162 = 11.066, p <
      0.001 for the whole curve, and F2;72 = 7.126, p < 0.005 for the refilling phase.
      A significant contrast was found next between S20-40 and the control day (p <
      0.001 whole curve; p < 0.005 refilling phase only), as well as between S20-40 and
      S0-20 (p < 0.001 whole curve; p < 0.025 refilling phase only). CONCLUSION: We
      conclude that smoking two cigarettes does not disturb the fatty meal-induced GB
      contraction in healthy humans. Subsequent GB refilling is delayed if smoking
      takes place during the late phase of the postprandial GB contraction.

PMID- 8273802
TI  - Organic nitrates in portal hypertension.
AB  - In conclusion, chronic administration of organic nitrates, allowing for a nitrate
      free interval each day, to cirrhotic patients reduces portal pressure with a
      variable, dose-dependent effect on azygos blood flow. The mechanisms of portal
      pressure reduction may vary according to the different doses and severity of
      liver disease. No studies to date have used dose-titration to determine the
      optimal beneficial effects in an individual patient, but some have at least
      compared the effect of different doses. Perhaps an end-point of mean arterial
      blood pressure reduction to 70 mm Hg could be suggested for future studies. The
      prophylactic benefit of nitrates for variceal bleeding still remains to be tested
      by controlled clinical trials. However, several problems in this evaluation need
      to be addressed, including patient compliance, selection of responders,
      evaluation of treatment, dose, and the duration of treatment. In contrast to the
      diminished expectations of propranolol for the prevention of rebleeding, there is
      mounting evidence of a major role for nitrates.

PMID- 8273803
TI  - Biphasic diurnal periodicity in bleeding from peptic ulcer.
AB  - OBJECTIVE: To evaluate if there was periodicity in the manifestations of
      gastrointestinal bleeding (hematemesis and melena). METHOD: This is a multicenter
      prospective study carried out in the Endoscopy Units of eight hospitals. At the
      time of the emergency endoscopy, the following data were collected: age, sex,
      endoscopic diagnosis, solar hour of the first hematemesis (vomiting of bright red
      or tarry black material) and of the first melena (black or bloody soft stools),
      and any drugs taken during the week before the bleeding episode, regardless of
      the dose. RESULTS: 806 patients were studied. Bleeding was from peptic ulcer in
      405 patients (50%), from esophageal varices in 197 (24%), and from other sources
      in the remainder. Analysis using single cosinor statistics showed a nonrandom
      distribution in bleeding from peptic ulcer, whether presenting first with
      hematemesis (p = 0.02) or melena (p = 0.03). There were two peaks at 6:45 AM and
      6:45 PM for hematemesis and at 7:25 AM and 7:25 PM for melena, representing a
      biphasic diurnal (ultradian) rhythm. CONCLUSIONS: This study shows that bleeding
      due to peptic ulcer has a biphasic diurnal periodicity. This has potential
      importance for the pathogenesis of bleeding, for the management of
      gastrointestinal hemorrhage and the administration of drugs known to cause peptic
      ulcer bleeding.

PMID- 8273804
TI  - Identification of gastric contractions from the cutaneous electrogastrogram.
AB  - OBJECTIVE: The objective of this study was to investigate whether gastric
      contractions in the fasting and fed state can be identified from the cutaneous
      electrogastrogram. METHODS: Simultaneous measurements of gastric myoelectrical
      and manometric activities were made in 10 healthy female volunteers from 1:00 AM
      to 9:45 AM. For manometric recording, a catheter incorporating solid state
      transducers was used. Cutaneous electrogastrography (EGG) was used for
      myoelectrical recording. All EGG data from 1:00 AM to 7:30 AM that occurred
      during motor quiescence, all EGG data that occurred during antral contractions,
      and 2-h EGG data after breakfast given at 7:30 AM were quantitatively analyzed
      and compared with each other. The EGG in three specific periods (fasting without
      antral contractions, fasting with contractions, and postprandial) was
      characterized by four parameters that include frequency, power, and stabilities
      of the frequency and power. RESULTS: 1) the peak power of the postprandial EGG
      was, respectively, 12.5 dB (about 2-fold increase in amplitude) and 6.8 dB (about
      1-fold increase in amplitude) higher than that during motor quiescence (p < 0.05)
      and motor activity in the fasting state; 2) the dominant frequency of the
      postprandial EGG was, respectively, 6% and 13% higher than that during motor
      quiescence and motor activity (p < 0.05) in the fasting state; 3) the peak power
      of the fasting EGG was 48% more unstable during motor activity than motor
      quiescence (p < 0.05); 4) the stability of the EGG frequency was not
      significantly different during the three different periods. CONCLUSION: The EGG
      provides important and useful information for the assessment of gastric motility.
      An unstable EGG peak power is indicative of gastric contractions in the fasting
      state. An increase in EGG peak power and/or dominant frequency after a solid test
      meal suggests a normal postprandial gastric motility.

PMID- 8273805
TI  - Measurement of portal systemic shunting by oral and per-rectal administration of
      [123I]iodoamphetamine, and clinical use of the results.
AB  - OBJECTIVE. We used a method by which the portal shunt index via the superior
      mesenteric vein (SI-S) and that via the inferior mesenteric vein (SI-I) could be
      evaluated simultaneously. The clinical usefulness of the method was studied.
      METHODS: Scintigraphy was done 3 h after subjects took an enteric-coated capsule
      containing [123I]iodoamphetamine. At that time, the radionuclide was injected
      into the rectum. Counts for the lungs and the liver were used to calculate the
      two shunt indices. RESULTS: The mean SI-S and SI-I tended to be higher for
      disorders that were more severe, increasing in the order of chronic persistent
      hepatitis, chronic aggressive hepatitis, and cirrhosis. In cirrhotic patients,
      the SI-I was higher than the SI-S (p < 0.001). The SI-S and SI-I were both higher
      in cirrhotic patients with esophageal varices than in such patients without
      varices (p < 0.05 and < 0.001). The SI-S and SI-I were higher in cirrhotic
      patients with ascites than in such patients without ascites (p < 0.001 and <
      0.01). Correlation between either of these indices and classical indicators of
      functional reserve was high. The correlation of SI-S with the Child-Turcotte
      classification and total bilirubin level was higher than the correlation of the
      SI-I and these indicators of functional reserve. CONCLUSIONS: This method permits
      assessment of the portal hemodynamics in a relatively noninvasive way, and is
      clinically meaningful.

PMID- 8273806
TI  - Interferon-gamma production specific for hepatitis B virus antigen by
      intrahepatic T lymphocytes in patients with acute and chronic hepatitis B.
AB  - OBJECTIVES: Studies were undertaken to determine whether intrahepatic lymphocytes
      have a greater cellular immune response specific for hepatitis B virus (HBV)
      antigen than peripheral blood lymphocytes in HBV-infected man. METHODS: HB
      nucleocapsid antigen-stimulated interferon-gamma (IFN-gamma) production of
      lymphocytes was measured in acute self-limited hepatitis (AH) (eight cases) and
      chronic hepatitis (CH) (14 cases). RESULTS: In both patient groups, basal IFN
      gamma levels without any stimulation were higher in the hepatic T cells than in
      the peripheral T cells. The values in cultures from blood and liver were larger
      in AH than in CH. Alternatively, IFN-gamma response to HBcAg and HBeAg was less
      in hepatic T cells than in the corresponding blood cultures; T cell response was
      HLA class II restricted. Cell flow cytometry study showed that in all patient
      groups, percentages of CD3+, CD8+, and HLA-DR+ cells were significantly greater
      in liver than in peripheral blood, whereas the proportion of hepatic CD4+ cells
      was decreased, compared with that in peripheral CD4+ cells. CONCLUSIONS: These
      findings suggest that liver infiltrates are already activated in vivo to produce
      IFN-gamma, particularly in patients with AH. The changes in the proportion of
      lymphocyte subsets may be responsible for the altered IFN-gamma response of
      hepatic T cells.

PMID- 8273807
TI  - The effect of indomethacin on the secretion of human salivary epidermal growth
      factor.
AB  - Ulceration associated with nonsteroidal anti-inflammatory drug (NSAID) use is a
      common problem in elderly patients. The postulated cause of NSAID ulceration is
      multifactorial but is probably related to the inhibition of the cyclo-oxygenase
      pathway and a subsequent decrease in mucosal prostaglandin levels. Epidermal
      growth factor (EGF), on the other hand, has been shown to be gastroprotective,
      stimulating DNA synthesis, and preventing ASA-induced gastric ulceration. Since
      EGF is important in gastric mucosal protection, we questioned whether the
      potential ulcerogenic properties of indomethacin were related in part to
      decreasing salivary EGF. Twenty healthy male volunteers with no gastrointestinal
      complaints received indomethacin 50 mg P.O. t.i.d. for 3 consecutive days. Saliva
      and serum were collected before indomethacin treatment and repeated 2 h after the
      last indomethacin dose. Stimulated salivary samples were collected for 15 min in
      fasted subjects and assayed for EGF, whereas serum indomethacin levels were
      determined by high-performance liquid chromatography. EGF levels significantly
      decreased by 33% after indomethacin (p < 0.03), and this decrement was linearly
      related to serum indomethacin concentrations (r = 0.58; p < 0.048). Salivary
      output did not change after indomethacin treatment. Based on this data, we
      concluded that indomethacin's ulcerogenic properties may be related to its
      prostaglandin inhibitory properties as well as its ability to decrease salivary
      EGF output.

PMID- 8273808
TI  - Shared strengths.

PMID- 8273809
TI  - Hospital smoking bans may help patients quit.

PMID- 8273810
TI  - Adjusting priorities, PRN.

PMID- 8273811
TI  - Breaking the silence.

PMID- 8273812
TI  - Decoding the ACLS algorithms.

PMID- 8273813
TI  - Obtaining a urine specimen from a conduit urostomy.

PMID- 8273814
TI  - The nurse intrapreneur. How to innovate from within.

PMID- 8273815
TI  - Viral hepatitis. Anatomy of a diagnosis.

PMID- 8273816
TI  - Johnny comes home.

PMID- 8273818
TI  - Books of the year.

PMID- 8273817
TI  - When the family can't let go.

PMID- 8273819
TI  - New changes from within.

PMID- 8273820
TI  - Memoirs of a traveling nurse.

PMID- 8273821
TI  - Confusion over illegible orders.

PMID- 8273822
TI  - Decimal point dangers.

PMID- 8273824
TI  - Society of Perinatal Obstetricians 14th Annual Meeting. Las Vegas, Nevada,
      January 24-29, 1994. Abstracts.

PMID- 8273823
TI  - Rebecca's ride.

PMID- 8273825
TI  - Hominid enamel thickness: I. The Krapina Neandertals.
AB  - Dental x-rays were taken of isolated and in situ adult molar teeth of the Krapina
      Neandertal (n = 63) and of recent and contemporary molars (n = 423). The
      radiographs were digitized at high resolution (1,024 x 1,520 x 8 bits) with a 35
      mm solid state scanner. Ratios of enamel cap area to the underlying dentinal
      pulpal area were determined and comparisons were made between average ratios for
      the Neandertal and contemporary molars. Neandertal molars had significantly
      smaller ratios than did contemporary teeth (P < 0.05). It is suggested that the
      smaller ratios represent relatively thinner enamel for Neandertals and that the
      thin enamel may have been caused by a metabolic depression that resulted in
      reduced enamel quantity (hypoplasia). Alternatively, the observed differences may
      be related to expanded pulps seen in various stages of taurodontism.

PMID- 8273826
TI  - Hominid radius from the middle Pliocene of Lake Turkana, Kenya.
AB  - A nearly complete left radius, KNM-ER 20419, was recovered from middle Pliocene
      sediments east of Lake Turkana, Kenya in 1988. Ape-like characteristics of the
      fossil include an eccentrically positioned articular fovea, relatively long
      radial neck, wide distal metaphysis, and large brachioradialis crest. The
      robustness of the radial neck in proportion to the radial head, and the semilunar
      shape of the distal diaphysis, however, clearly distinguish KNM-ER 20419 as
      hominid. The distal articular surface possesses a larger area for radius-lunate
      articulation than for radius and scaphoid, a radiocarpal arrangement that is
      associated with increased wrist adduction among quadrumanous climbers. Since this
      morphology is also found in hylobatids, Pongo, and other early
      australopithecines, it is argued to be plesiomorphic for hominoids. This further
      supports the argument that vertical climbing was an important locomotor behavior
      among both early hominoids and our more immediate prebipedal ancestors.

PMID- 8273827
TI  - Hypertrophy of the acetabulo-cristal buttress in Homo sapiens.
AB  - In the early 1970s, excavation at the King site, a contact period Mississippian
      village in northwest Georgia, yielded the skeletal remains of a robust male (King
      65) possessing marked hypertrophy of the acetabulo-cristal buttress. The buttress
      is morphologically similar to that of Plio-Pleistocene Homo but it is accompanied
      by an anatomically modern degree of thickening of the gluteal table of the ilium.
      Although the degree of cortical thickness of the gluteal table of the ilium is
      apparently species-specific, hypertrophy of the acetabulo-cristal buttress is
      developmental and may be expressed in all species of Homo.

PMID- 8273828
TI  - Sex hormone levels and body hair growth in !Kung San and Kavango men from
      Namibia.
AB  - The relation between hair growth and levels of sex hormones in serum and saliva
      was investigated in 256 !Kung San and Kavango men (ages 18 to 39 years) from
      Namibia/Southern Africa. Serum concentrations of total testosterone (Tser), 5
      alpha-dihydrotestosterone (DHT), and estradiol (E2) as well as the level of
      bioavailable non-SHBG-bound testosterone in the saliva (Tsal) were determined by
      radioimmunoassay. The distribution and density of scalp and facial hair as well
      as the development of terminal hair on the chest, abdomen, pubic area, arms,
      fingers, and legs were categorized using objective criteria. Covariance analyses
      revealed marked differences in the distribution of body hair in the San and the
      Negro sample. This is partly explained by a significant influence of androgen and
      estrogen levels on the growth of terminal hair. DHT and the ratio DHT/Tser are
      significantly positively related to midphalangeal hair growth and negatively to
      pubic hair development. Tsal, the bioavailable fraction of total testosterone,
      exerts a weak positive influence on the degree of arm and leg hair growth; the
      most significant positive effect on the growth of abdominal, arm, and leg hair in
      our samples is caused by E2. The ratio Tser/E2 correlates significantly
      negatively with the arm and leg hair development and the ratio DHT/E2 with the
      degree of abdominal, pubic, arm, and leg hair, whereas lower DHT concentrations
      occur in men with stronger hair development.

PMID- 8273829
TI  - Sexual dimorphism in schoolchildren of the Villa IAPI neighborhood (Quilmes,
      Buenos Aires, Argentina).
AB  - Villa IAPI is a poor neighborhood of about 5,000 inhabitants in the overpopulated
      conurbano bonaerense at the outskirts of the city of Buenos Aires. Most of the
      adult male residents are construction workers; the rest are temporary workers,
      underemployed, or unemployed. The inhabitants of Villa IAPI suffer the effects of
      many adverse socio-economic conditions, including poor nutrition, deficient
      sanitation, and inadequate medical care. Seven anthropometric variables were
      measured on 765 children from 6 to 14 years old to test for the presence of an
      altered pattern of sexual dimorphism. It was found that there were practically no
      sex differences in standing height and upper-arm muscle circumference. In some
      age groups, there was a weak but significant sexual dimorphism in body weight and
      sitting height. The greatest and most persistent dimorphism was found in head
      circumference, and in triceps and subscapular skinfolds. In all except two age
      groups, head circumference in males was significantly greater than in females.
      The other dimorphic variables (body weight, sitting height, and triceps and
      subscapular skinfolds) showed the opposite relationship. Essentially, females
      showed increments in subcutaneous fat, while reduced growth in muscle and bone
      was evident in males. The hypothesis of "better female canalization" can explain
      the altered dimorphic pattern found in the malnourished Villa IAPI population.

PMID- 8273830
TI  - Accuracy tests of tooth formation age estimations for human skeletal remains.
AB  - Estimations of age from tooth formation standards for a large (n = 282) sample of
      subadult skeletal remains from a 19th century historic cemetery sample were
      analyzed. The standards of Moorrees et al. (1963a,b) for the permanent and
      deciduous teeth, and Anderson et al. (1976) for the formation of permanent
      dentition were employed in a variety of combinations to calculate mean dental
      ages. Tests of accuracy and bias were made on a small sample (n = 17) of
      personally identified individuals, and age of attainment scores were compared to
      age of prediction scores for each individual. The resulting dental age
      distributions for the skeletal sample were compared to documented burial records
      for the cemetery to determine the representativeness of the skeletal sample.
      These comparisons showed little difference between age of attainment versus age
      of prediction methodologies. The standards of Moorrees et al. (1963a,b) were
      observed to provide the most accurate estimates of age with a standard deviation
      of one-half year. The standards of Anderson et al. (1976), while easier to use
      and more extensive, are problematic in that the original reference sample begins
      at three years of age, while the sample used by Moorrees and colleagues begins at
      birth. The skeletal age distributions compare well to the overall chronological
      age distribution for the cemetery. These results affirm that tooth formation age
      estimates for subadult skeletal remains from archaeological or forensic samples
      provide accurate assessments of age at both the individual and population level.

PMID- 8273831
TI  - Enamel thickness of human maxillary molars reconsidered.
AB  - Forty-four modern human maxillary molars (M1 = 21, M2 = 12, and M3 = 11) were
      sectioned through the mesial cusps in a plane perpendicular to the cervical
      margin of the crown. Eight measurements of enamel thickness as well as bucco
      lingual (BL) and mesio-distal (MD) diameters were recorded for each tooth in
      order to investigate differences in these dimensions between tooth categories.
      Uni- and multi-variate analyses revealed first maxillary molars to have generally
      thinner enamel than second or third upper molars, especially with regard to the
      occlusal basin. Furthermore, the decrease of MD diameters from anterior to
      posterior is greater than that of BL diameters. Principal Component Analysis
      using enamel thickness measurements resulted in complete separation of first
      molars, while second and third maxillary molars showed a certain amount of
      overlap. This finding casts doubt on using an overall measure of "molar enamel
      thickness" derived from mixed samples of molars for taxonomic purposes. There
      appears to be a relationship between bite force and enamel thickness such that
      posterior molars, where masticatory forces are stronger, have thicker enamel than
      anterior teeth. It is suggested that the gradient of enamel thickness between
      (and within) teeth in extant and extinct species may thus provide further
      information about relative wear resistance as well as the biomechanical
      constraints of the orofacial skeleton.

PMID- 8273832
TI  - Canine size and shape in male anthropoid primates.
AB  - While studies of canine dimorphism in primates are common, only a few have
      examined canine tooth size independently within each sex. Recently, Greenfield
      and Washburn (Am. J. Phys. Anthropol. 84:17-34, 1991) proposed that there are two
      types of male canines which reflect different allometric scaling patterns of
      canine crown height against canine occlusal dimensions. They also suggest that
      proportional canine shape, measured as canine crown height (or projection)
      relative to the occlusal dimensions, provides an estimate of the canine's
      function as a weapon, though they provide no test of this hypothesis. This
      analysis critically examines the claim that there are two types of male canines
      among anthropoids. It then tests the hypothesis that relative male canine size
      (measured against body weight) and proportional canine shape are related to
      estimates of intermale competition, diet, and substrate (used as a surrogate
      measure of predation pressure). While there is strong taxonomic variation in
      canine size and shape among male anthropoids, no evidence is found for two
      discrete canine types. Rather, within families and subfamilies, canine dimensions
      scale isometrically against body weight and against each other, with a continuum
      of canine shapes among different taxa. While variation in male canine size is
      associated with intermale competition and substrate, even when taxonomic
      variation is controlled, variation in proportional canine shape is not. Neither
      canine size nor shape are generally associated with variation in diet.

PMID- 8273833
TI  - Enamel microstructure and molar wear in the greater galago, Otolemur
      crassicaudatus (Mammalia, Primates).
AB  - This study describes the molar enamel microstructure of the greater galago, based
      on SEM study of four individuals. Galago molar enamel consists primarily of
      radially oriented Pattern 1 prisms. However, the most superficial enamel is
      characterized by regions of poorly developed prisms or nonprismatic enamel, and
      Pattern 3 prisms can be found at depths intermediate and deep to the enamel
      surface. Orientations of prism long axes relative to wear surfaces differ among
      functionally distinct regions (cuspal facets, Phase I/II facets, and crushing
      basins). Consequently, orientations of enamel crystallites relative to these
      surfaces also differ. Because crystallites are the structural unit involved in
      enamel abrasion, these differences in orientation may have important effects on
      molar wear patterns. Crystallite orientations differ most between cuspal facets
      and Phase I/II facet surfaces. Cuspal facets are characterized by near surface
      parallel interprismatic and surface-oblique prismatic crystallites. Previous
      experimental studies suggest that this arrangement is most resistant to wear when
      surface-normal (compressive) loads predominate. In contrast, prismatic and
      interprismatic crystallites intercept Phase I/II facet surfaces obliquely, an
      arrangement expected to resist abrasion when surface-parallel (shearing) loads
      predominate. Superficial enamel is preserved at most basin surfaces, indicating
      that these regions are subject to comparatively little abrasive wear. These
      results support the hypothesis that galago occlusal enamel is organized so as to
      resist abrasion of different functional regions, a property that may prove
      important in maintaining functional efficiency. However, this largely reflects
      constraints of occlusal topography on a microstructure typical of many mammals
      and thus does not appear to represent a structural innovation.

PMID- 8273834
TI  - Health care issues of the 1990s: what are our responsibilities as surgeons?

PMID- 8273835
TI  - The 1942 fire at Boston's Cocoanut Grove nightclub.
AB  - The year 1992 marked the 50th anniversary of one of the worst civilian disasters
      in American history. On November 28, 1942, fire destroyed Boston's Cocoanut Grove
      nightclub, killing 491 people and sending hundreds more to area hospitals. The
      disaster came at a unique time in the history of burn care and resulted in a
      number of important advances in burn treatment, including the first comprehensive
      descriptions of inhalation injury, improvements in topical treatment of burn
      wounds, resuscitation of shock, use of antibiotics, and understanding of the
      metabolic response to injury. In addition, the fire stimulated organization of
      burn care facilities, public safety legislation, and burn prevention. The history
      of the fire is reviewed, emphasizing its role in stimulating advances that formed
      some of the foundations of modern burn treatment.

PMID- 8273836
TI  - Etiology and consequences of respiratory failure in thermally injured patients.
AB  - Inhalation injury predisposes burn patients to pneumonia, respiratory failure,
      and death, but the incidence and consequences of respiratory failure in the
      absence of inhalation injury are not well known. In a review of 529 burn patients
      admitted over a 4-year period, patients with inhalation injury had a 73%
      incidence of respiratory failure (hypoxemia, multiple pulmonary infections, or
      prolonged ventilator support) and a 20% incidence of adult respiratory distress
      syndrome (ARDS). In patients without inhalation injury, respiratory failure
      developed in 5% of patients and ARDS in 2% (both p < 0.001). Patients with
      respiratory failure display a high incidence of multiple organ failure and
      mortality (27% to 50%), regardless of the presence of inhalation injury. All
      patients who died had multiple organ failure. This review demonstrates that
      respiratory failure, regardless of its cause, frequently leads to multiple organ
      failure and death. Inhalation injury, in the absence of respiratory failure, does
      not appear to contribute to mortality.

PMID- 8273837
TI  - Pneumonia: cause or symptom of postinjury multiple organ failure?
AB  - Recent studies have shown that selective gut decontamination can reduce the
      incidence of pneumonia, but this does not decrease multiple organ failure (MOF)
      or mortality. These findings have prompted the hypothesis that pneumonia is an
      inconsequential symptom of MOF. To test this, we prospectively evaluated 123 high
      risk trauma patients (mean Injury Severity Score = 36.2 +/- 1.5). Organ
      dysfunction, scored daily according to a 12-point scale, ultimately developed in
      28 (23%) patients. Major infections were diagnosed, based on strict criteria, in
      59 patients (48%), and pneumonia developed in 52 patients (43%). Pneumonia was
      significantly associated with MOF (82% of patients with MOF versus 30% of
      patients without MOF, p < 0.0001). In 14 (50%) of the patients with MOF,
      pneumonia preceded a significant rise (greater than or equal to 3) in serial MOF
      scoring. Of note, 10 (71%) of these patients died. Among the remaining 14
      patients with MOF, 10 developed pneumonia, but this was associated with a minimal
      increase (less than or equal to 2) in MOF scoring (3 patients died). These data,
      by temporal association with MOF scoring, implicate pneumonia in precipitating or
      significantly worsening organ failure in 50% of the patients who developed MOF.

PMID- 8273838
TI  - Continuous arteriovenous hemodiafiltration in postoperative and traumatic renal
      failure.
AB  - Management of acute renal failure (ARF) in surgical patients has relied on
      supportive measures including hemodialysis and peritoneal dialysis. An
      alternative technique currently available is continuous arteriovenous
      hemodiafiltration (CAVH-D). Records of 44 surgical patients with ARF who were
      treated with CAVH-D in our surgical intensive care unit from 1989 to 1992 were
      reviewed. Thirty-five patients underwent emergency operations, and 4 patients
      underwent elective operations. Thirty-three patients were hemodynamically
      unstable immediately prior to the institution of CAVH-D, making hemodialysis a
      contraindication. A total of 565 CAVH-D days with an average of 13 days per
      patient were evaluated. Seventeen patients survived, with recovery of renal
      function in 13 patients. Vascular access was obtained via 227 percutaneous
      femoral catheters and 4 Scribner shunts. Seven vascular complications occurred,
      including arteriovenous fistula, pseudoaneurysm, limb ischemia, femoral artery
      hemorrhage, and femoral vein thrombosis. Based on these data, we conclude that
      CAVH-D is a safe and effective alternative in surgical patients with ARF.

PMID- 8273839
TI  - Candida sepsis in surgical patients.
AB  - Candidemia in critically ill patients is a significant source of mortality. To
      identify perioperative risk factors accounting for patient death, we performed a
      retrospective study of 46 surgical patients with fungemia during the period from
      1981 to 1990. Twenty patients survived (43%), and 26 died (57%). Mortality was
      associated with age older than 46 (p < 0.02, unpaired Student's t-test) and
      concomitant renal failure, hepatic failure, postoperative shock, or adult
      respiratory distress syndrome (p < 0.0001, p < 0.0001, and p < 0.05,
      respectively, chi 2 test). Survival was not influenced by the presence of
      diabetes, chronic obstructive pulmonary disease, gastrointestinal hemorrhage,
      pneumonia, alcohol consumption, steroid use, or enteral/parental nutrition.
      Bacterial speticemia developed in 26 patients (11 lived, 15 died) and typically
      preceded or was concomitant with the onset of fungal sepsis (88%). Candida
      albicans was the fungal species most commonly isolated from blood cultures (30 of
      46). Its was cultured from other sites in addition to blood in 30 patients.
      Candidemia carries a higher risk of mortality in older patients and in those with
      multiple organ dysfunction. Other immunocompromised conditions such as diabetes
      and steroid use did not increase mortality. These findings suggest that the
      pathogenicity of Candida sepsis is not solely related to opportunistic
      superinfections but may reflect failure of other host defense mechanisms.
      Moreover, the frequent occurrence of bacterial septicemia prior to the
      development of Candida sepsis further emphasizes the importance of fungal
      surveillance cultures to detect early fungal colonization in the critically ill.

PMID- 8273840
TI  - Comparison of an intravenous bolus of famotidine and Mylanta II for the control
      of gastric pH in critically ill patients.
AB  - The effects of the intravenous bolus administration of famotidine versus the
      administration of Mylanta II liquid every 2 hours on the pH of the gastric
      antrum, body, and fundus for 24 hours were compared in 10 critically ill patients
      admitted to the intensive care unit with isolated cranial trauma. Patients
      received 30 mL of Mylanta II every 2 hours via nasogastric tube for 24 hours,
      followed by administration of 20 mg of intravenous bolus famotidine every 12
      hours for the subsequent 24-hour period. pH of the gastric antrum, body, and
      fundus was monitored continuously using a three antimony pH electrode/nasogastric
      tube assembly. Gastric pH data were analyzed for the percentage of time pH was
      less than 4 and median pH for the antrum, body, and fundus for each 24-hour
      period. The percentage of time pH was less than 4 was significantly less in the
      antrum and body of the stomach during famotidine therapy (8.9% +/- 3.6% and 24.9%
      +/- 6.9%, respectively) compared with Mylanta II (39.1% +/- 6.7% and 57.6% +/-
      8.5%, respectively, both p < 0.005), but was not significantly different in the
      fundus (famotidine: 25.3% +/- 7.8%; Mylanta II: 28.3% +/- 6.5%). Median gastric
      pH for 24 hours was significantly greater in the antrum and body of the stomach
      during famotidine therapy (7.8 +/- 0.2 and 6.8 +/- 0.6, respectively) compared
      with Mylanta II (4.5 +/- 0.6 and 3.7 +/- 0.9, respectively, p < 0.005 and p <
      0.01, respectively), but was not significantly different in the fundus
      (famotidine: 5.9 +/- 0.8; Mylanta II: 5.4 +/- 0.7). The data indicate that an
      intravenous bolus of famotidine every 12 hours is more effective than Mylanta II
      liquid every 2 hours administered via a nasogastric tube in maintaining gastric
      pH above 4 in critically ill patients. Famotidine produces a uniform increase in
      gastric pH throughout the stomach, whereas Mylanta II controls only proximal
      gastric pH, probably related to fundic pooling of antacid in the supine position.

PMID- 8273841
TI  - Transrectal ultrasound of rectal tumors.
AB  - Since preoperative staging of rectal tumors is important in planning treatment,
      we evaluated transrectal ultrasound (TRUS) staging of rectal neoplasms. In 35
      consecutive rectal tumors, we compared TRUS staging results with final pathologic
      staging. TRUS predicted the degree of tumor invasion in 19 of 24 patients (79%)
      and the presence or absence of lymph node metastasis in 11 of 15 patients (73%).
      TRUS overestimated the degree of tumor invasion in four patients (17%) and
      underestimated invasion in one patient (4%). The depth of tumor invasion was
      correctly predicted in all 14 tumors located within 6 cm from the anal verge,
      but, beyond 6 cm, only 5 of 10 tumors (50%) were staged correctly (p = 0.005). In
      the group of 11 patients who underwent preoperative radiotherapy, pretreatment
      TRUS predicted the depth of tumor invasion in only six patients (55%) and
      overestimated tumor invasion in five patients (45%), suggesting that nearly half
      of these tumors were downstaged by radiotherapy. TRUS accurately predicts the
      degree of tumor invasion, especially in tumors closer to the anal verge, allowing
      for better treatment planning in patients with low to middle rectal neoplasms.

PMID- 8273842
TI  - Establishing a histologic basis for false-negative mammograms.
AB  - In order to explore the histology of false-negative mammograms, 264 consecutive
      patients with breast cancer were retrospectively reviewed until 100 patients with
      palpable cancers were identified. These patients were imaged by a dedicated
      mammographer within 6 months prior to biopsy. Nine of the 100 patients had
      "negative" readings originally, with 6 of the 9 still regarded as negative when
      re-examined after full knowledge of the tumor location. Histologic review of
      these six tumors showed a diffusely infiltrative pattern in five patients (three
      with invasive lobular carcinomas and two with multifocal, invasive ductal
      carcinomas). Although background breast density always serves in a critical
      relationship with tumor density on film, only one of these six patients showed a
      severe degree of mammographic breast density. Diffuse histology should be
      recognized as a principal cause of false-negative mammograms. Since mammography
      is based solely on anatomic contrasts, diffuse histology could easily prevent the
      perfection of this modality, calling attention to the need for improved adjunct
      imaging techniques.

PMID- 8273843
TI  - Prognostic implications of DNA index in patients with stage III cutaneous
      melanoma.
AB  - DNA flow cytometry of the lymph node metastases from 56 patients was used to
      retrospectively evaluate the prognostic significance of DNA ploidy in patients
      with stage III melanoma. The findings were correlated with traditional prognostic
      factors and patient survival. Multivariate regression analysis revealed that, in
      addition to the number of positive lymph nodes and patient gender, the DNA index
      was a significant predictor of patient survival (all p < 0.03). Within this
      cohort of patients, the patients with the poorest prognoses were those with DNA
      indices greater than 2 (at least tetraploid), more than three positive lymph
      nodes, and male gender. There was a significant survival difference among the
      patients having zero, one, or two of these risk factors (p < 0.001). Our results
      indicate that DNA analysis of melanoma metastases by flow cytometry provides an
      additional discriminating factor for predicting patient outcome after therapeutic
      lymph node dissection. This information may be useful in directing patients with
      stage III melanoma at higher risk for recurrence into clinical trials of more
      aggressive systemic adjuvant therapy.

PMID- 8273844
TI  - Outcome effect of adherence to operative principles of Nissen fundoplication by
      multiple surgeons. The Department of Veterans Affairs Gastroesophageal Reflux
      Disease Study Group.
AB  - Fifty-eight patients participated in a multi-institutional study designed to
      assess the outcome of Nissen fundoplication when performed for complicated
      disease by a variety of surgeons with varied skill and experience with compliance
      to established technical principles. All patients had an abnormal 24-hour pH
      study and mucosal injury on endoscopy. The surgical procedures were performed in
      8 Veterans Administration hospitals by surgical residents supervised by surgical
      faculty, after initial agreement on 10 operative principles for the Nissen
      fundoplication. The mean symptomatic scores at 52 and 104 weeks improved
      significantly compared with the preoperative score (p < 0.0001). There was
      significant improvement in total percent time at pH below 4 at 52 weeks (p <
      0.01) and 104 weeks (p < 0.01). There was significant improvement in the grade of
      esophagitis at 1 year (p < 0.0001). Compliance was greater than 90% for 7 of 10
      principles of repair. In conclusion, a Nissen fundoplication resulted in relief
      of symptoms in 93% of patients and a 77% rate of healing of esophagitis. These
      results in complicated reflux disease were achieved by a variety of surgeons with
      varied experience in antireflux surgery.

PMID- 8273845
TI  - Impact of adjunctive testing on the diagnosis and clinical course of patients
      with acute appendicitis.
AB  - The diagnosis of acute appendicitis is usually made from the history and physical
      examination. Recently, abdominal ultrasonography (US), laparoscopy, computerized
      tomography (CT), and barium enema (BE) have been used in the preoperative
      evaluation of patients with presumed appendicitis in order to improve the
      diagnostic accuracy. However, the usefulness of these tests in verifying the
      diagnosis of appendicitis has not been established. We reviewed the medical
      records of 203 patients who underwent appendectomy. One hundred patients were
      surgically treated before 1984 (group I) and 103 patients underwent surgery after
      1988 (group II). Patients in group II were more likely to have preoperative US,
      laparoscopy, CT, or BE (24 in group II versus 3 in group I, p < 0.05). When
      groups I and II were compared, the rates of perforation (27% versus 20%), normal
      appendectomy (8% versus 11%), and the interval between admission and operation
      (12.2 hours versus 10.7 hours) and length of hospitalization (5.0 days versus 5.1
      days) were not significantly different. We concluded that although adjunctive
      testing may be beneficial in selected patients, its routine use in patients
      suspected of having appendicitis cannot be advocated at present.

PMID- 8273846
TI  - Surgical management of cecal diverticulitis.
AB  - Ninety surgical cases of cecal diverticulitis at the University of Hawaii
      hospitals were reviewed from 1980 to 1991. Seventy-eight percent of the study
      group were of Asian descent, with a mean age of 41.7 years. Right lower quadrant
      pain and tenderness were the only constant findings, occurring in 86 and 87 of
      the 90 patients, respectively. The most common preoperative diagnosis was acute
      appendicitis, occurring in 73% of patients. A right colectomy or cecectomy was
      performed in 49 patients, an appendectomy in 29, and a diverticulectomy in 10.
      Seventeen complications occurred, only 1 of which was in the appendectomy group.
      Follow-up of up to 10 years was successful in 27 of 29 appendectomy patients,
      only 4 of whom had recurrent pain. There were no instances of a missed cecal
      carcinoma. We concluded that in those patients in whom carcinoma can be ruled out
      and in whom there is no evidence of abscess formation, appendectomy combined with
      postoperative antibiotics is a safe and effective method for the treatment of
      cecal diverticulitis.

PMID- 8273847
TI  - Abnormal gallbladder nuclear ejection fraction predicts success of
      cholecystectomy in patients with biliary dyskinesia.
AB  - The management of patients with symptoms consistent with biliary tract disease
      who do not have gallstones is difficult. We retrospectively reviewed the charts
      of 18 patients who underwent cholecystokinin cholescintigraphy at our institution
      to determine if this procedure was reliable in identifying patients who would
      benefit from cholecystectomy. All patients underwent biliary screening, and a
      gallbladder ejection fraction of less than or equal to 35% was considered
      abnormal. None of the patients had evidence of gallstones by ultrasound. There
      were 11 patients with abnormal ejection fractions. All 11 patients (100%) had
      "classic" biliary colic and underwent cholecystectomy. The pathologic diagnosis
      was chronic cholecystitis in every patient. All patients had complete relief of
      their symptoms postoperatively with a mean follow-up of 10 months. There were six
      patients with normal ejection fractions. Only one patient in this group had
      "classic" biliary colic. This patient had a gallbladder ejection fraction of 38%
      and endoscopic evidence of gastritis. This patient remains symptomatic despite H2
      blockade. The remaining five patients had nonspecific right upper quadrant or
      epigastric pain. These patients had endoscopic evidence of gastritis, and
      symptoms were relieved with H2 blockade. The remaining patient had an
      indeterminate scan due to radioactivity in the duodenum overlying the gallbladder
      and was excluded from this analysis. Cholecystokinin cholescintigraphy is a
      useful test in identifying those patients with biliary dyskinesia or acalculous
      cholecystitis who will benefit from cholecystectomy.

PMID- 8273848
TI  - The questionable utility of mandatory screening for the human immunodeficiency
      virus.
AB  - Trauma patients have been identified as a high-risk group for human
      immunodeficiency virus (HIV) infection, particularly those patients with
      penetrating injuries from urban violence. We prospectively evaluated more than
      2,000 trauma patients for HIV infection at our ACS-certified trauma center and
      report the results. Between September 1987 and December 1991, 2,004 patients were
      admitted to our trauma unit. All patients underwent HIV antibody assay by
      protocol. Three patients had positive test results, and all were confirmed as
      true positives. Two patients were known at the time of their trauma to be HIV
      positive, and the third had engaged in high-risk behavior. No health care worker
      reported inoculation with or mucosal exposure to HIV from any of these patients.
      In our trauma unit, the prevalence of HIV infection was only 0.15%. More than
      $74,000 was spent on screening without demonstrable benefit to the patients or
      increased protection for the trauma team. Routine testing of patients for HIV can
      be justified to establish epidemiologic parameters and in the case of high-risk
      groups, but it is not cost-effective in low-risk groups. Persistent testing of
      populations at low risk is a futile expenditure of precious health care dollars
      and is of questionable utility.

PMID- 8273849
TI  - Oral contrast is not necessary in the evaluation of blunt abdominal trauma by
      computed tomography.
AB  - The administration of oral contrast (OC) is widely recommended for computed
      tomography (CT) of the abdomen in patients with blunt trauma. The purpose of this
      study was to determine whether routine abdominal CT scans performed without OC
      were associated with diagnostic error in patients with blunt trauma. Four hundred
      ninety-two patients were identified from our Trauma Registry who had CT scans for
      the evaluation of blunt abdominal trauma between January 1988 and December 1991.
      Seventy-six percent (372) of the CT scans were interpreted as negative, and 24%
      (120) were considered positive. OC was used in 8 (1.6%) of 492 patients. Only 1
      of 372 patients whose initial non-OC--enhanced scan was negative subsequently
      required surgery. There were 5 bowel injuries among the 42 patients who underwent
      an abdominal operation; in none would the use of OC have ensured the preoperative
      diagnosis. We found that the omission of OC did not represent a disadvantage to
      patients with blunt trauma undergoing a routine abdominal CT scan. Potential time
      delays and the hazards associated with the use of OC were minimized.

PMID- 8273850
TI  - Risk of abdominal septic complications after feeding jejunostomy placement in
      patients undergoing splenectomy for trauma.
AB  - Compared with total parenteral nutrition, enteral feeding via jejunostomy reduces
      septic complications in patients with severe trauma. However, violation of the
      bowel with insertion of a jejunostomy tube may increase the risk of intra
      abdominal abscess (IAA), particularly if no simultaneous gastrointestinal tract
      injury exists. The records of 123 patients requiring splenectomy for trauma at a
      level I trauma center during a 6-year period (1986 to 1992) were reviewed to
      examine the incidence of IAA in patients with and without simultaneous
      jejunostomy placement in the presence and absence of gastrointestinal tract
      injuries. Thirty patients had jejunostomies placed (J), and 93 did not (NoJ).
      There were no significant differences between the groups in age, Abdominal Trauma
      Index, Injury Severity Score, or transfusion requirements. The incidence of IAA
      was not significantly different between the J and NoJ groups in the presence or
      absence of gastrointestinal tract injuries. Thus, jejunostomy placement does not
      increase the incidence of IAA after splenectomy regardless of the presence of a
      gastrointestinal tract injury.

PMID- 8273851
TI  - Preliminary report on videothoracoscopy in the evaluation and treatment of
      thoracic injury.
AB  - A prospective trial of videothoracoscopy was conducted at an urban trauma center
      between February 1992 and February 1993 to determine the efficiency of this less
      invasive method of evaluation and treatment. Twenty-four consecutive patients
      with chest trauma (penetrating, n = 22; blunt, n = 2) were examined
      thoracoscopically for clotted hemothorax that otherwise would have been treated
      with thoracotomy (n = 9), suspected diaphragmatic injury (n = 10), and continued
      bleeding (n = 5). To ensure maximal exposure, general anesthesia with a double
      lumen endotracheal tube was used in each patient. Clotted hemothorax was
      successfully evacuated in eight of nine patients (89%). Diaphragmatic laceration
      was suspected in 10 patients (2 abnormal chest radiographs, 8 proximity
      penetrating wounds) and confirmed thoracoscopically in 5. In four patients,
      diaphragmatic lacerations were successfully repaired with thoracoscopic
      techniques. Five patients underwent thoracoscopy for continued hemorrhage
      (greater than 1,500 mL per 24 hours) after tube thoracostomy. Intercostal artery
      injury was confirmed in all patients, and diathermy provided hemostasis in three
      patients without thoracotomy. No complications occurred. These data suggest the
      following: (1) Videothoracoscopy is an accurate, safe, and minimally invasive
      method for the assessment of diaphragmatic injuries, control of continued chest
      wall bleeding, and early evacuation of clotted hemothorax. (2) This technique
      should be used more frequently in patients with thoracic trauma. (3) Technical
      advances may expand the therapeutic role of thoracoscopy.

PMID- 8273852
TI  - Diagnostic and therapeutic thoracoscopy: lessons from the learning curve.
AB  - A variety of video-assisted thoracic operations are being reported with
      increasing frequency. Problems encountered during the development of this
      technology have received less attention. During the course of 27 months, 69
      consecutive patients underwent minimally invasive procedures at our institution.
      Conversion to thoracotomy was required in 16 of 49 (33%) patients undergoing
      diagnostic procedures and 1 of 20 (5%) patients undergoing therapeutic
      interventions. Fewer complications occurred in those patients with diagnostic
      procedures (10 of 49, 20%) versus therapeutic interventions (10 of 20, 50%; p =
      0.01). Logistic regression analysis showed chronic obstructive pulmonary disease
      to be an independent risk factor for complications. The mean postoperative stay
      was 7.9 +/- 6.8 days for diagnostic and 12.8 +/- 9.7 days for therapeutic
      interventions (p = 0.02). As new technologic improvements were introduced, the
      mean hospital stay decreased (first 10 months: 14.6 +/- 10.0 days, 10 to 20
      months: 9.8 +/- 9.6 days, more than 20 months: 5.2 +/- 3.0 days, p < 0.004). The
      surgeon's thoracoscopic experience was not as strongly predictive (5 or fewer
      cases: 8.9 +/- 5.9 days, 6 to 15 cases: 13.1 +/- 12.6 days, more than 15 cases:
      5.0 +/- 2.0 days). Although thoracoscopic surgery is promising, the potential for
      problems requires careful surgical judgment and expertise in dealing with
      thoracic complications.

PMID- 8273853
TI  - Combined laparoscopic and endoscopic management of cholelithiasis and
      choledocholithiasis.
AB  - With the advent of laparoscopic cholecystectomy, optimal management of common
      duct stones remains controversial. Seven hundred six patients underwent
      laparoscopic cholecystectomy in our institution from January 1990 through January
      1992. From this group of patients, 50 were identified as having clinical or
      radiographic evidence of common duct stones. Thirty-one patients demonstrated
      preoperative risk factors for common duct stones and underwent preoperative
      endoscopic retrograde cholangiopancreatography (ERCP). The risk factors included
      jaundice (19%), pancreatitis (23%), elevated liver function tests (52%), and
      ultrasound evidence of choledocholithiasis (6%). Preoperative ERCP was performed
      in 94% of patients. There were two failures due to periampullary diverticula.
      Common duct stones were identified in 18 patients (62%) and successfully removed
      by endoscopic sphincterotomy in all of these patients. Nineteen patients were
      found to have unsuspected common duct stones on intraoperative cholangiography.
      Eighteen patients (95%) underwent successful ERCP and endoscopic sphincterotomy
      with stone extraction. Overall, major morbidity was 2% and included one patient
      who experienced endoscopic sphincteroplasty. The three endoscopic failures were
      managed by open common duct exploration, laparoscopic duct exploration, and
      combined laparoscopic and open common duct exploration. We conclude that combined
      laparoscopic and endoscopic therapy is a viable option for the management of
      cholelithiasis with choledocholithiasis.

PMID- 8273854
TI  - Role of laparoscopy in the evaluation of abdominal trauma.
AB  - This prospective study was designed to determine if laparoscopy is a safe and
      accurate method for abdominal evaluation in the trauma patient. Thirty-two
      patients who presented with blunt or penetrating trauma and who were scheduled
      for celiotomy based on clinical evaluation constituted the study group. The
      patients underwent diagnostic laparoscopy prior to exploratory celiotomy. One of
      6 (16%) patients with blunt abdominal trauma and 5 of 26 (19%) patients with
      penetrating abdominal trauma had significant injuries that were found at the time
      of operation but not visualized during laparoscopy. The missed injuries involved
      the liver, pancreas, stomach, duodenum, small bowel, small bowel mesentery,
      ureter, and urinary bladder. The correlation between the laparoscopist and the
      trauma surgeon as to the need to perform a celiotomy was 97%. Complications
      occurred in 2 of 32 patients. Eleven patients with anterior abdominal penetrating
      injuries had no evidence of penetration of the abdominal cavity at laparoscopy,
      and had no evidence of injury at celiotomy. We concluded that (1) there are areas
      within the abdominal cavity that cannot be accurately visualized with
      laparoscopy; (2) the evaluation of penetration of the peritoneal cavity from
      anterior penetrating injury appears to be accurate; (3) a number of injuries were
      not identified; and (4) further investigation of this procedure for the
      evaluation of abdominal trauma is required to assess its safety and accuracy.

PMID- 8273855
TI  - Impact of endoscopic therapy on outcome of operation for bleeding peptic ulcers.
AB  - Since elective surgery for bleeding peptic ulcer disease has declined, the
      surgical opinion is that patients who undergo emergency operation have more
      advanced disease and possibly a poorer outcome. We examined current mortality for
      surgical correction of upper gastrointestinal (UGI) bleeding from peptic ulcer
      disease. Between July 1, 1986, and December 31, 1990, 1,213 patients had
      esophagogastroduodenoscopy for UGI bleeding (659 with peptic ulcer disease, 219
      with gastroesophageal varices, 152 with esophagitis, 83 with other causes, and
      100 with no source found). Of 110 patients with peptic ulcer disease treated by
      endoscopic methods, bleeding was controlled in 90, and 20 required operation for
      failed endoscopic control. Another 22 patients had primary operation for exigent
      bleeding with diagnostic endoscopy only. The overall results in our series
      compared favorably with two pre-therapeutic endoscopy index series (Nottingham,
      1982; University of Pittsburgh, 1982). Our operation rate was 6%, with a
      mortality rate of 7%, compared with operation rates of 15% to 27%, with mortality
      rates of 21% to 22% in the historical control series. In conclusion, we found
      that: (1) endoscopic control of UGI bleeding from peptic ulcer disease has
      decreased the incidence of operation compared with historical series; (2) overall
      operative mortality is decreasing; and (3) the major postoperative complication
      is rebleeding.

PMID- 8273856
TI  - Thrombolytic therapy for catheter-related thrombosis.
AB  - Thrombosis of the central venous system (CVT) occurs in 20% to 30% of patients
      with indwelling catheters. This complication is usually treated with
      anticoagulation, extremity elevation, and catheter removal. Thirty-eight patients
      with CVT at our institution were treated with thrombolytic therapy to rapidly
      resolve symptoms and avoid removal of the catheters. Complete clot lysis occurred
      in 36 of 38 patients (95%) within 1 to 5 days (mean: 2.4 days). Symptoms resolved
      with clot resolution. Thrombolytic therapy detected stenoses in 22 patients.
      Angioplasty was successful in 64% of these patients. Five catheters were removed.
      Complications occurred in six patients: nonfatal pulmonary embolus, three
      bleeding episodes, pain with infusion of urokinase, and an episode of septic
      phlebitis. This experience suggests that thrombolytic therapy is safe, rapidly
      resolves symptoms of thrombosis, uncovers anatomic abnormalities amenable to
      angioplasty, and allows central venous catheters to remain in place despite
      central venous thrombosis.

PMID- 8273857
TI  - Rational approach to postoperative transfusion in high-risk patients.
AB  - An appropriate threshold for transfusion in patients with coronary artery disease
      has not been defined. Our purpose was to determine: (1) the effects of
      preoperative volume loading; (2) postoperative function and oxygen delivery
      (DO2); (3) an appropriate transfusion threshold based on observed DO2 in high
      risk patients undergoing abdominal aortic aneurysm (AAA) repair, bypass of
      aortoiliac disease (AOD), distal bypass, or carotid endarterectomy (CEA).
      Preoperative volume loading increased cardiac output (CO) in all groups by 15% to
      22%. Postoperative CO was unchanged from optimal preoperative values except in
      the CEA group, in which it decreased. Systemic vascular resistance decreased in
      the AAA and AOD groups. The decrease in postoperative DO2 in all groups (25% to
      31%) was related to a decrease in hemoglobin. Despite marginal (less than 11
      mL/kg/min) postoperative DO2 in more than a third of patients, there was no
      compensatory increase in CO. Thus, after optimization of function by volume
      loading, red cell transfusion may be the only way to increase DO2. Hemoglobin
      levels of 10 to 12 g/dL may be required for adequate DO2 when ventricular
      function is markedly impaired.

PMID- 8273858
TI  - Simultaneous surgical management of aortic and renovascular disease.
AB  - The results of simultaneous elective infrarenal aortic reconstruction and
      renovascular surgery were retrospectively reviewed in 102 patients who
      consecutively underwent operation. The perioperative mortality rate (0 to 54
      days) was 5% (5 of 102). Renal function had returned to baseline or was improved
      at discharge in 89 of 97 (92%) surviving patients. The intraoperative use of
      renal hypothermia was an independent predictor of improved postoperative renal
      function, by multivariate analysis. Twenty-five of 29 (86%) patients with severe
      hypertension had improvement in their blood pressure on the same or fewer
      medications postoperatively (p = 0.0005). A retroperitoneal incision was
      associated with less intraoperative crystalloid fluid administration (p = 0.03),
      more rapid postoperative resumption of an oral diet (p = 0.04), and better long
      term survival (p = 0.02) when compared with a transperitoneal incision. We
      conclude that the simultaneous repair of infrarenal aortic pathology and
      renovascular lesions is associated with an acceptable perioperative morbidity and
      preserves or improves renal function in the majority of patients. The frequent
      use of renal hypothermia and careful consideration of the route of operative
      exposure will lead to optimal results.

PMID- 8273859
TI  - Randomized, prospective comparison of first- and second-generation cephalosporins
      as infection prophylaxis for cardiac surgery.
AB  - Surgical wound infections after cardiovascular surgery may be life threatening
      and are resource intensive. Second-generation cephalosporins are purported to
      have a broader antimicrobial spectrum than first-generation cephalosporins and,
      therefore, may be more efficacious for infection prophylaxis. We have conducted a
      randomized prospective study of 702 patients undergoing open heart surgery to
      test the hypothesis that the second-generation cephalosporin, cefuroxime, will be
      more efficacious for infection prophylaxis than the first-generation
      cephalosporin, cefazolin. Patients were randomized to receive cefazolin 1 g
      intravenously every 8 hours for 48 hours begun 1 hour preoperatively plus 1 g
      after 4 hours of surgery (8 doses, n = 425) or cefuroxime 1.5 g 1 hour prior to
      surgery plus 1.5 g every 12 hours for 3 additional doses (4 doses, n = 277).
      Infection was defined as a draining wound with or without a positive culture.
      There was no difference in the wound infection rate between the groups (p =
      0.68). Chest wound infections occurred in 2.1% of patients treated with cefazolin
      and 2.9% of patients treated with cefuroxime (p = 0.79). The rate of true
      mediastinitis requiring exploration and drainage was 0.7% in both groups (p =
      0.084). Leg infections occurred in 6.6% of cefazolin-treated patients and 5.6% of
      cefuroxime-treated patients (p = 0.83). The second-generation cephalosporin,
      cefuroxime, did not reduce the incidence of wound infection when compared with
      the first-generation cephalosporin, cefazolin. Since institutional antibiotic
      acquisition and administration costs vary, careful analysis of these factors will
      allow determination of the most cost-effective infection prophylaxis regimen in
      cardiac surgery.

PMID- 8273860
TI  - Confirmation of the association of human papillomavirus with human colon cancer.
AB  - The human papillomavirus (HPV) has been shown to be associated with neoplasms of
      the human colon using immunohistochemistry and in situ hybridization. We now
      report our use of the polymerase chain reaction and Southern blotting to
      investigate that same association. We selected 38 carcinomas, 21 adenomas, and 24
      normal mucosal samples for the current study. Tissue sections were prepared, and
      then DNA was extracted and subjected to 40 cycles of amplification using Thermus
      aquaticus DNA polymerase and a set of degenerate primers. Amplified products were
      analyzed by agarose gel electrophoresis and Southern blotting. The L1 region of
      the HPV genome was identified in 13 of 38 carcinomas (32%), 8 of 21 adenomas
      (38%), and 2 of 24 normal biopsy specimens (8%). These observations validate our
      previous results and confirm the presence of HPV in human colon mucosa and tumors
      of that mucosa.

PMID- 8273861
TI  - Adjuvant hepatic arterial infusion chemotherapy after curative resection of
      colorectal liver metastases.
AB  - We performed a prospective study of adjuvant hepatic arterial infusion
      chemotherapy after resection of colorectal liver metastases. We placed hepatic
      arterial infusion ports in 20 consecutive patients undergoing curative resection
      of colorectal liver metastases. The chemotherapy regimen was a weekly bolus of 5
      fluorouracil (15 mg/kg) for 6 months. The median follow-up has been 33 months.
      Nine of the 18 evaluable patients (50%) have developed recurrent colorectal
      cancer. The liver was the only site of failure in 3 of 18 patients (17%), and
      extrahepatic recurrences occurred in 6 of 18 patients (33%). All patients without
      recurrence are alive. The median survival of the patients without recurrent
      disease is 39 months, compared with 27 months for those with recurrent metastatic
      disease (p < 0.01). In patients who received adjuvant hepatic arterial infusion
      chemotherapy compared with historical controls treated with surgery alone, we
      have observed a decreased incidence of recurrent disease after liver resection
      for metastases. We recommend that patients who undergo hepatic resection for
      colorectal metastases be considered for postoperative adjuvant chemotherapy to
      decrease the likelihood of recurrence and to improve survival.

PMID- 8273862
TI  - New horizons in the diagnosis and treatment of breast cancer using magnetic
      resonance imaging.
AB  - A new nuclear magnetic resonance imaging (MRI) technique, Rotating Delivery of
      Excitation Off-resonance (RODEO), has been developed to assist surgeons in the
      diagnosis and treatment of breast cancer. A nonrandomized, prospective study of
      100 patients with a high suspicion of breast cancer was conducted; these patients
      were examined by RODEO and conventional breast imaging, including mammography.
      Forty-one breasts were removed by mastectomy; each pathologic specimen was
      examined by sectional analysis. This study was undertaken to determine the extent
      that RODEO can aid in detecting breast tumors (including multicentric disease)
      and in evaluating candidates for conservative breast surgery. RODEO detected 85
      pathologically confirmed lesions, 64 of which proved to be malignant. RODEO had a
      sensitivity of 95%, compared with a sensitivity of 58% for conventional imaging.
      More study is needed to determine distinguishing MRI characteristics that are
      suspicious for malignancy. RODEO may be used clinically to assess multicentricity
      and response to chemotherapy.

PMID- 8273863
TI  - Revascularization of the limbs with urokinase and TEC catheter endarterectomy for
      occluded bypass grafts.
AB  - Occlusion of a femoral-popliteal or a femoral-tibial bypass graft on a prior
      occluded superficial femoral artery or the popliteal artery (in cases of ischemia
      of the legs) creates a complicated problem that may result in limb loss. The
      revascularization of such limbs with a repeat femoral-tibial or peroneal bypass
      is difficult and results in a high rate of limb loss from failure of the repeat
      grafts. Therefore, attempts were made to re-open the grafts through urokinase
      administration and thrombolysis for the grafts. To address the distal critical
      stenosis, or occlusion, the urokinase administration and thrombolysis were
      followed by endovascular endarterectomy using a thromboembolytic catheter (TEC).
      From 1990 to 1992, the above protocol was followed with 15 patients. In all
      patients, the protocol included 24 to 48 hours of urokinase administration with
      60,000 to 120,000 U of urokinase per hour. A distal pathology was detected in all
      15 patients, of whom 8 had complete occlusion at the site of distal anastomosis,
      7 had critical stenosis ranging from 90% to 99%, and 1 was found to have a
      proximal critical stenosis at the femoral-graft junction. TEC catheter
      endarterectomy was performed to address the problem of occlusion and critically
      stenosed distal anastomotic lesions; a 100% success rate was immediately
      achieved, with flow being re-established to the distal limb. Fourteen of 15
      patients remained well revascularized for more than 1 year. One patient
      experienced re-occlusion after 8 months; the occlusion was re-opened using the
      same technique of urokinase administration and the use of the TEC catheter, in
      which case the graft subsequently remained open. The longest follow-up of one
      patient is more than 2 years, during which time the graft has stayed open. With
      the aforementioned results, after revascularization of the ischemic limbs from
      occluded bypass grafts, it is strongly recommended that urokinase administration,
      along with TEC endovascular endarterectomy, be used to establish the circulation
      when occluded grafts threaten limb loss.

PMID- 8273864
TI  - Rectal tumors: treatment with a posterior approach.
AB  - Treatment of large sessile polyps or tumors of the rectum is a challenging
      surgical problem. A retrospective review of the posterior surgical approach for
      the treatment of rectal tumors was conducted to assess the efficacy of this
      operative technique. Thirty-three patients were reviewed. Thirteen patients
      underwent transanal excision, and 3 of these patients had malignant disease. One
      patient returned to the operating room because of postoperative bleeding. Twelve
      patients underwent transsacral excision of tumors, 6 of which were malignant
      lesions in the mid to high rectum. One patient developed a fistula. One benign
      tumor recurred. Eight patients underwent abdomino-sacral excision, and seven of
      these were for rectal cancer. Local control was unsuccessful with this technique
      in one patient. There were no deaths in this series. The complication rate was
      acceptable, and the morbidity of local pain was offset by sphincter preservation
      and return of normal bowel function. This approach seems very useful for a
      variety of rectal tumors.

PMID- 8273865
TI  - Colorectal cancer in patients under 30 years of age. Contributors to the
      Southwestern Surgical Congress Unusual Case Registry.
AB  - The Southwestern Surgical Congress (SWSC) recently initiated a registry of
      unusual cases. The registry was created to collect information on patients with
      uncommon conditions treated by members of the Congress. The registry is intended
      to be a source of clinical information for the members, as well as a tool for the
      conduct of retrospective and prospective clinical and epidemiologic studies. As
      the first project, we collected data on patients with colorectal cancer who were
      30 years of age or less at the time of diagnosis. Letters were sent to all
      members of the SWSC soliciting information about such patients. Data collection
      sheets were subsequently mailed to those who responded to the letter. The data
      sheets asked for demographic data, as well as pertinent anamnestic, clinical, and
      staging information. Operative reports, pathology reports, and paraffin-embedded
      tissue blocks were also requested. Twenty-four members contributed a total of 55
      patients to the registry. There were 23 males (age range: 14 to 30 years) and 32
      females (age range: 16 to 30 years). In 37 patients, factors assumed to
      predispose to colorectal cancer were identified. The most common predisposing
      factor was smoking. There were 12 right colon tumors, 24 left colon tumors, and
      11 rectal tumors. According to the TNM classification, 6 patients had stage I
      disease, 15 patients had stage II disease, 17 patients had stage III disease, and
      17 patients had stage IV disease. Tissue blocks from tumor and adjacent bowel
      will be examined to address the issue of a possible genetic predisposition for
      cancer at the molecular level, in these young patients. We will also assess the
      independent influence of age on prognosis by comparing the actuarial survival and
      recurrence rates in patients from the registry with data from older patients who
      are matched for the presence of other known prognostic factors. The Unusual Case
      Registry will provide the members of the Congress with a valuable database of
      clinical information. Furthermore, this method of compilation will facilitate the
      collection of relatively large patient samples over a short period of time. This
      will greatly facilitate the conduct of original and relevant collaborative
      prospective studies of uncommon diseases within the framework of the SWSC.

PMID- 8273866
TI  - Is liver transplantation indicated for cholangiocarcinoma?
AB  - Liver transplantation for unresectable primary liver cancer has met with
      skepticism due to early aggressive recurrences occurring in early series from
      many centers. The primary tumors for which transplantation has been performed
      have been hepatocellular carcinoma and cholangiocarcinoma. In an attempt to
      improve these poor results, we instituted a protocol with adjuvant chemotherapy
      and radiotherapy after liver transplantation for cholangiocarcinoma. Between
      December 1984 and December 1992, 701 patients underwent 795 liver transplants.
      Seventeen patients had a diagnosis of cholangiocarcinoma and form the basis of
      this review. Three patients were excluded from the study, two because of early
      postoperative deaths, and one because of an unknown bony metastasis present at
      the time of transplant. Eleven patients have experienced a recurrence, and 7 of
      these died secondary to their recurrence. Three patients are alive with no
      evidence of disease 44 months, 31 months, and 28 months, respectively, after
      transplant. The 1-year survival rate in these patients is 53%, and the disease
      free survival rate is 40%. Patients were able to tolerate the adjuvant
      chemotherapy and radiotherapy without apparent morbidity or mortality.
      Unfortunately, this protocol does not appear to provide significant benefit.
      Until a better adjuvant therapy protocol is developed, it is questionable whether
      unresectable cholangiocarcinoma should be considered an indication for liver
      transplantation.

PMID- 8273867
TI  - Metastatic carcinoma in the cirrhotic liver.

PMID- 8273868
TI  - The Weller-Ash nitrous oxide apparatus.

PMID- 8273869
TI  - Symposium--The Australian Incident Monitoring Study.

PMID- 8273870
TI  - The Australian Incident Monitoring Study. Errors, incidents and accidents in
      anaesthetic practice.
AB  - Human error is a pervasive and normal part of everyday life and is of interest to
      the anaesthetist because errors may lead to accidents. Definitions of, and the
      relationships between, errors, incidents and accidents are provided as the basis
      to this introduction to the psychology of human error in the context of the work
      of the anaesthetist. Examples are drawn from the Australian Incident Monitoring
      Study (AIMS). An argument is put forward for the use of contemporaneous incident
      reporting (eliciting relevant contextual information as well as details of use to
      cognitive psychologists), rather than the use of accident investigation after the
      event (with the inherent problems of scant information, altered perception and
      outcome bias). A classification of errors is provided. "Active" errors may be
      classified into knowledge-based, rule-based, skill-based and technical errors.
      Different strategies are required for the prevention of each type and it may now
      be useful to place more emphasis in anaesthetic practice on categories to which
      little attention has been directed in the past. "Latent" errors make an enormous
      contribution to problems in anaesthesia and several categories are discussed
      (e.g. environment, physiological state, equipment, work practices, personnel
      training, social and cultural factors). An approach is provided for the
      prevention and management of errors, incidents and accidents which allows
      clinical problems to be categorized, the relative importance of various
      contributing factors to be established, and appropriate preventative strategies
      to be devised and implemented on the basis of priorities determined from the AIMS
      data. Accidents cannot be abolished; however, an understanding of the factors
      underlying them can lead to the rational direction of resources and effort to
      prevent them and minimise their effects.

PMID- 8273871
TI  - The Australian Incident Monitoring Study: an analysis of 2000 incident reports.
AB  - The Australian Patient Safety Foundation was formed in 1987; it was decided to
      set up and co-ordinate the Australian Incident Monitoring Study as a function of
      this Foundation; 90 hospitals and practices joined the study. Participating
      anaesthetists were invited to report, on an anonymous and voluntary basis, any
      unintended incident which reduced, or could have reduced, the safety margin for a
      patient. Any incident could be reported, not only those which were deemed
      "preventable" or were thought to involve human error. The Mark I AIMS form was
      developed which incorporated features and concepts from several other studies.
      All the incidents in this symposium were reported using this form, which contains
      general instructions to the reporter, key words and space for a narrative of the
      incident, structured sections for what happened (with subsections for circuitry
      incidents, circuitry involved, equipment involved, pharmacological incidents and
      airway incidents), why it happened (with subsections for factors contributing to
      the incident, factors minimising the incident and suggested corrective
      strategies), the type of anaesthesia and procedure, monitors in use, when and
      where the incident happened, the experience of the personnel involved, patient
      age and a classification of patient outcome. Enrollment, reporting and data
      handling procedures are described. Data on patient outcome are presented; this is
      correlated with the stages at which the incident occurred and with the ASA status
      of the patients. The locations at which the incidents occurred and the types of
      procedures, the sets of incidents analysed in detail and a breakdown of the
      incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273872
TI  - The Australian Incident Monitoring Study. Which monitor? An analysis of 2000
      incident reports.
AB  - The role of monitors in patients undergoing general anaesthesia was studied by
      analysing the first 2000 incidents reported to the Australian Incident Monitoring
      Study; 1256 (63%) were considered applicable to this study. In 52% of these a
      monitor detected the incident first; oximetry (27%) and capnography (24%)
      detected over half of the monitor detected incidents, the electrocardiograph 19%,
      blood pressure monitors 12%, a low pressure (circuit) alarm 8%, and the oxygen
      analyser 4%. Of the other monitors used, 5 first detected 1-2% of incidents, and
      the remaining 8 less than 0.5% each. The oximeter would have detected over 40% of
      the monitor detected incidents had its more informative modulated pulse tone
      always been relied upon instead of the "bleep" of the ECG. A theoretical analysis
      was then carried out to determine which of an array of 17 monitors would reliably
      have detected each incident had each monitor been used on its own and had the
      incident been allowed to evolve. To facilitate "scoring" of monitors, the
      incidents were categorized empirically into 60 clinical situations; 40% of
      applicable incidents were accounted for by only 5 clinical situations, 60% by 10
      and nearly 80% by 20. 98% were accounted for by the 60 situations. A pulse
      oximeter, used on its own, would theoretically have detected 82% of applicable
      incidents (nearly 60% before any potential for organ damage). These figures for
      capnography are 55% and 43% and for oximetry and capnography combined are 88% and
      65%, respectively. With the addition of blood pressure monitoring these become
      93% and 65%, and of an oxygen analyser, 95 and 67%. Other monitors, including the
      ECG, each increase the yield by by less than 0.5%. The international monitoring
      recommendations and those of the Australian and New Zealand College of
      Anaesthetists are thoroughly vindicated by the patterns revealed in this study.
      The priority sequence of monitor acquisition for those with limited resources
      should be stethoscope, sphygmomanometer, oxygen analyser if nitrous oxide is to
      be used, pulse oximeter, capnograph, high pressure alarm, and, if patients are to
      be mechanically ventilated, a low pressure alarm (or spirometer with alarm); an
      ECG, a defibrillator, a spirometer and a thermometer should be available.

PMID- 8273873
TI  - The Australian Incident Monitoring Study. The pulse oximeter: applications and
      limitations--an analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      were analysed with respect to the role of the pulse oximeter. Of these 184 (9%)
      were first detected by a pulse oximeter and there were a further 177 (9%) in
      which desaturation was recorded. Of the 1256 incidents which occurred in
      association with general anaesthesia 48% were "human detected" and 52% "monitor
      detected". The pulse oximeter was ranked first and detected 27% of these monitor
      detected incidents; this figure would have been over 40% if an oximeter had
      always been used and its more informative modulated pulse tone relied upon
      instead of that of the "bleep" of the ECG. The pulse oximeter is the "front-line"
      monitor for endobronchial intubation, the fourth most common incident in
      association with general anaesthesia (it detected 87% of the 76 cases in which it
      was in use). It also played an invaluable role as a "back-up" monitor in 40 life
      threatening situations in which "front-line" monitors (e.g. oxygen analyser, low
      pressure alarm, capnograph) were either not in use, were being used incorrectly
      or failed. Other situations detected, in order of frequency of detection, were:
      circuit disconnection, circuit leak, desaturation (severe shunt), oesophageal
      intubation, aspiration and/or regurgitation, pulmonary oedema, endotracheal tube
      obstruction, severe hypotension, failure of oxygen delivery, hypoxic gas mixture,
      hypoventilation, anaphylaxis, air embolism, bronchospasm, malignant hyperthermia,
      and tension pneumothorax.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273874
TI  - The Australian Incident Monitoring Study. The capnograph: applications and
      limitations--an analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      were analysed with respect to the role of the capnograph. One hundred and fifty
      seven (8%) were first detected by a capnograph and there were a further 18 (1%)
      in which capnography was contributory. Of the 1256 incidents which occurred in
      association with general anaesthesia 48% were "human detected" and 52% "monitor
      detected". The capnograph was ranked second and detected 24% of these monitor
      detected incidents; this figure would have been nearly 30% if a correctly
      checked, calibrated capnograph had always been used. The capnograph is a "front
      line" monitor for oesophageal intubation, failure of ventilation, anaesthetic
      circuit faults, gas embolism, sudden circulatory collapse and malignant
      hyperthermia. It is a valuable "back-up" monitor when other monitors (e.g. low
      pressure alarm, pulse oximeter) are not in use, are being used incorrectly or
      fail. Such situations, in order of frequency of detection were: circuit-leak,
      overpressure of the breathing circuit, bronchospasm, leak of ventilator-driving
      gas into the patient circuit, aspiration and/or regurgitation and
      hypoventilation. There were 20 reports of "failure", over two-thirds of which
      would not have occurred with appropriate checking and calibration. Seven were due
      to gas sampling problems and 6 to apnoea alarm failure. Two circuit leaks and 2
      faulty unidirectional valves were not detected; on 3 occasions problems occurred
      due to power failure, calibration problems, or misinterpretation of an
      alarm.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273875
TI  - The Australian Incident Monitoring Study. The electrocardiograph: applications
      and limitations--an analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      (AIMS) were analysed with respect to the role of the electrocardiograph (ECG). Of
      these, 138 (7%) were first detected by the ECG. Of the 1256 incidents which
      occurred in association with general anaesthesia (GA incidents) 48% were "human
      detected" and 52% "monitor detected", the ECG was ranked third and detected 121
      (19%) of these monitor detected GA incidents. However over 98% of incidents first
      detected by the ECG were heart rate changes; they would also have been detected
      by a pulse meter or pulse oximeter which would have supplied additional
      information about the adequacy of peripheral perfusion. The ECG is a "first-line"
      monitor in situations with the potential for myocardial ischaemia, complex
      dysrhythmias or altered myocardial conduction and should be used in all
      critically ill patients as well as those at significant risk of these problems.
      The ECG frequently detects incidents involving minor physiological trespass, such
      as simple heart rate and rhythm changes associated with anaesthetic agents. These
      incidents are generally detected relatively early in their evolution. AIMS data
      has confirmed, however, that the ECG has such poor sensitivity for serious
      physiological changes such as hypoxia, hypercarbia and hypotension that it cannot
      even be regarded as a useful "back-up" monitor for these problems. Indeed a
      "normal" ECG in a dangerous situation may lead to a degree of
      complacency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273876
TI  - The Australian Incident Monitoring Study. Blood pressure monitoring--applications
      and limitations: an analysis of 2000 incident reports.
AB  - Of the first 2000 incidents reported to the Australian Incident Monitoring Study,
      1256 occurred in relation to general anaesthesia and 81 of the latter were first
      detected by blood pressure (BP) monitoring. A further 25 incidents not associated
      with general anaesthesia were first detected by blood pressure monitoring, giving
      a total of 106. In the monitor detection of incidents in relation to general
      anaesthesia, BP monitoring ranked fourth after oximetry, capnography and low
      pressure alarms. On the other hand, 38 incidents in which the problem was
      primarily one of significant change in BP were first detected by means other than
      the BP monitor (20 clinically, 12 by pulse oximetry and 6 by ECG). Early
      detection rates of hypotension were 60% for invasive methods, 40% for automated
      non-invasive (NIBP) devices and 30% for manual sphygmomanometry. There were 21
      reports of BP monitor "failure"; the 11 of these which occurred with NIBPs
      involved unexplained false "low" or "high" readings and failure to detect
      profound hypotension, and led to considerable morbidity and at least one death.
      The 10 cases of invasive monitoring failure were predominantly due to mains power
      loss, hardware breakage or operator error. In a theoretical analysis of the 1256
      GA incidents, it was considered that on its own, BP monitoring would have
      detected 919 (73%), but in the vast majority, by the time this detection has
      occurred, potential organ damage could not be excluded. It is recommended that BP
      be measured at regular intervals dictated by clinical requirements (usually at
      least every five minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273877
TI  - The Australian Incident Monitoring Study. The oxygen analyser: applications and
      limitations--an analysis of 200 incident reports.
AB  - The first 2000 incidents reported to the Australian INcident Monitoring Study
      were analysed with respect to the role of the oxygen analyser; 27 (1%) were first
      detected by the oxygen analyser. All of these were amongst the 1256 incidents
      which occurred in association with general anaesthesia, of which 48% were "human
      detected" and 52% "monitor detected". The oxygen analyser was ranked 7th and
      detected 4% of these monitor detected incidents. This figure would have been much
      higher had the oxygen analyser been correctly used on more occasions. The oxygen
      analyser detected 10 ventilator-driving-gas leaks into the circuit, 6 hypoxic
      mixtures due to rotameter settings, 3 inappropriate nitrous oxide concentrations,
      2 disconnections and 1 leak at the common gas outlet, and 2 partial and 1 total
      failure of ventilation. In a theoretical analysis of these 1256 incidents it was
      considered that the oxygen analyser, used on its own, would have detected 114
      (9%), had they been allowed to evolve (3% before any potential for organ damage).
      In 4 incidents an oxygen analyser gave faulty readings, in 3 caused a leak and in
      one a total circuit obstruction; 5 incidents were not detected because the alarm
      had been disabled. Despite the advent of piped gas supplies, failure of gas
      delivery or delivery of a "wrong" gas mixture still occurs surprisingly
      frequently in current anaesthetic practice; hypoxic mixtures were supplied on 16
      occasions, other "wrong" mixtures on 23 and the oxygen supply failed on 7
      occasions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273878
TI  - The Australian Incident Monitoring Study. The stethoscope: applications and
      limitations--an analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      (AIMS) were analysed with respect to the role of the oesophageal or precordial
      stethoscope as a continuous monitor. There were 1099 of the 1256 incidents during
      general anaesthesia in which one might have been used in this way, but use was
      reported in only 65 cases (5%), predominantly during paediatric cases. In only
      one report, a cardiac arrest, was the stethoscope the first to detect the
      incident. In a theoretical analysis it was considered that the stethoscope, used
      on its own for continuous monitoring, could have detected 54% of the 1256
      incidents (almost 25% before any potential for organ damage), had they been
      allowed to evolve. However, AIMS data suggest that the actual yield using a
      stethoscope as a continuous monitor may be much lower than this, and that even
      the use of a "mobile" stethoscope can not be relied upon to detect oesophageal or
      endobronchial intubation. These reports confirm that there is limited use of the
      stethoscope for continuous monitoring in current anaesthetic practice in
      Australia; it has been superseded by the sophisticated electronic monitors now
      available. However, in areas with limited resources continuous auscultation with
      a stethoscope remains a basic requirement.

PMID- 8273879
TI  - The Australian Incident Monitoring Study. Crisis management--validation of an
      algorithm by analysis of 2000 incident reports.
AB  - Anaesthetists are called upon to manage complex life-threatening crises at a
      moment's notice. As there is evidence that this may require cognitive tasking
      beyond the information-processing capacity of the human brain, it was decided to
      try and develop a generic crisis management algorithm analogous to the "Phase I"
      immediate response routine used by airline pilots. Such an algorithm, based on
      the mnemonic "COVER ABCD, A SWIFT CHECK", was developed and refined over 3
      meetings, each attended by 60-100 anaesthetists and aviation psychologists. It
      was validated against 1301 relevant incidents among the first 2000 incidents
      reported to the Australian Incident Monitoring Study. It proved sufficiently
      robust and safe to recommend its general use as an initial response to any
      incident or crisis which occurs when a patient is breathing gas from an
      anesthetic machine. It requires a limited knowledge base and is easily learnt and
      rehearsed during the anaesthetist's working day. It will provide a functional
      diagnosis in over 99% of cases and will correct 62% of the problems in 40-60
      seconds. In the remaining 37% it will allow the anaesthetist to proceed with a
      "sub-algorithm", confident in the knowledge that some important step has not been
      missed. In just over 30% of incidents this will be for a problem familiar to all
      anaesthetists (e.g. laryngospasm, bradycardia); in just over 6% it will be for a
      less common, more complex, but finite, set of problems (3% cardiac arrest, 1% air
      embolism, 1% anaphylaxis, 1% for the remaining desaturations); in less than 1%
      diagnosis and correction will require a more complex checklist (e.g. for
      malignant hyperthermia, pneumothorax). The next stage, the development of
      specific sub-algorithms and a structured team approach for ongoing problems, is
      in progress.

PMID- 8273880
TI  - The Australian Incident Monitoring Study. Problems before induction of
      anaesthesia: an analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring study
      (AIMS) were examined to identify those incidents which occurred preoperatively
      (defined as occurring prior to the commencement of general or regional
      anaesthesia). The 35 incidents, representing 1.7% of the total, which occurred in
      this time period were analysed with a view to identifying areas in which current
      practice could be improved. Almost all incidents led to significant delays in
      operating lists, and 9 resulted in cancellation of surgery. A number of areas of
      concern specific to the preoperative period were identified. Inadequate
      coordination between surgical and anaesthetic staff in patient preparation was a
      frequent cause of preoperative incidents. Improvement in this area may reduce
      surgical delays and patient morbidity. Problems with premedication drugs resulted
      in 8 of the 35 incidents, and care must be taken in the prescription and
      administration of these drugs to minimise adverse effects on patients. Only 2
      cases of incorrect patient identification were reported. However, in view of its
      disastrous consequences, vigilance in patient identification by all members of
      the operating team, including the anaesthetist, is essential.

PMID- 8273881
TI  - The Australian Incident Monitoring Study. The "wrong drug" problem in
      anaesthesia: an analysis of 2000 incident reports.
AB  - Amongst the first 2000 incidents reported to the Australian Incident Monitoring
      Study, there were 144 incidents in which the "wrong drug" was nearly or actually
      administered to a patient. Thirty-three percent of the incidents involved
      ampoules and just over 40% syringes; in over half of the latter the syringes were
      of the same size, and also, in over half, they were correctly labelled. In 81% of
      the 144 incidents the "wrong drug" was actually given. This was more common with
      syringes (93%) than ampoules (58%). Thus the most common error was actually
      giving the wrong drug from a correctly labelled syringe. The most common drug
      involved was a muscle relaxant in both ampoule and syringe incidents. In 74% of
      all reports, there was the potential for serious harm to the patient; however no
      deaths were reported. Factors which contributed significantly to the incidents
      were similar appearance, inattention and haste. "Failure of communication" was a
      significant factor in syringe incidents when two or more staff were involved. The
      only significant factor which minimised the outcome was rechecking of the syringe
      or drug ampoule before giving the drug. Strategies suggested to address the
      "wrong drug" problem include education of staff about the nature of the problem
      and the mechanisms involved; colour coding of selected drug classes for both
      ampoules and syringes; the use of standardised drug storage, layout and selection
      protocols; having a drawing up and labelling convention; and the use of checking
      protocols.

PMID- 8273882
TI  - The Australian Incident Monitoring Study. Difficult intubation: an analysis of
      2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      were analysed with respect to the incidence and circumstances of problems with
      endotracheal intubation; 85 (4%) indicated difficulties with intubation. One
      third of these were emergency cases, one third involved an initially unassisted
      trainee and one fifth were outside normal working hours. Failure to predict a
      difficult intubation was reported in one third of the cases, with another quarter
      presenting serious difficulty despite preoperative prediction. Difficulties with
      ventilation were experienced in 1 in 7 of the 85 reports; there was one cardiac
      arrest, but no death. Endotracheal intubation was not achieved in one fifth of
      the cases. The commonest complications reported amongst the 85 incidents were
      oesophageal intubation (18 cases), arterial desaturation (15 cases), and reflux
      of gastric contents (7 cases). Emergency trans-tracheal airways were required in
      5 cases. Obesity, limited neck mobility and mouth opening, and inadequate
      assistance together accounted for two thirds of all the contributing factors. The
      most successful intubation aid in this series was a gum elastic bougie. A
      capnograph contributed to management in 28% and a pulse oximeter in 12% of the
      cases in which they were used. The most serious desaturations were associated
      with accidental oesophageal intubation. These data suggest a lack of reliable
      preoperative assessment techniques and skills for the prediction of difficult
      intubations. They also suggest the need for a greater emphasis on ensuring that
      the necessary equipment is available, and on teaching and learning drills for
      difficult intubation and any associated difficulty with ventilation.

PMID- 8273883
TI  - The Australian Incident Monitoring Study. Oesophageal intubation: an analysis of
      2000 incident reports.
AB  - There were 35 oesophageal intubations in the first 2000 incidents reported to the
      Australian Incident Monitoring Study (AIMS). These reports confirm existing
      impressions that misplacement of the endotracheal tube can occur in trained as
      well as untrained hands, and that auscultation is an unreliable test. On the
      other hand, the value of capnography is emphasised, with no false positives in
      the 16 cases in which the instrument was used. There was one false negative. Over
      the 4 years of the AIMS study, reports have declined in frequency. It is possible
      that the early detection of oesophageal intubation by capnography has altered its
      status to the extent that anaesthetists no longer regard it as a "critical"
      incident. It is highly recommended that the presence of the expected
      concentration of carbon dioxide in expired air be confirmed by capnography
      immediately after any endotracheal intubation.

PMID- 8273884
TI  - The Australian Incident Monitoring Study. Problems related to the endotracheal
      tube: an analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      were analysed with respect to problems with the endotracheal tube; 189 (9%) were
      reported. The most common problem was endobronchial intubation which accounted
      for 42% of these 189 reports; endobronchial intubation was the most common cause
      of arterial desaturation in the 2000 incidents. Obstructions and oesophageal
      intubation each accounted for 18% of the 189 problems with tubes. The remainder
      was made up of disconnections and leaks (7% each), misplacements other than
      endobronchial or oesophageal (4%), inappropriate choice of tube (3%), cuff
      herniation (1%), failure to deflate the cuff and foreign body in the tube (0.5%
      each). The pulse oximeter and capnograph first detected 58% of these incidents; a
      further 25% were detected clinically. The pulse oximeter is the "front-line"
      monitor for endobronchial intubation, and the capnograph the "front-line" monitor
      for oesophageal intubation, disconnection and obstruction. Recommendations are
      made for how to prevent problems and how to determine the nature of those that do
      occur.

PMID- 8273885
TI  - The Australian Incident Monitoring Study. Problems with ventilation: an analysis
      of 2000 incident reports.
AB  - A review of the first 2000 incidents reported to the Australian Incident
      Monitoring Study found 317 incidents which involved problems with ventilation.
      The major portion (47%) were disconnections; 61% of these were detected by a
      monitor. Monitor detection was by a low circuit pressure alarm in 37% but this
      alarm failed to warn of non-ventilation in 12 incidents (in 6 because it was not
      switched "on" and in 6 because of a failure to detect the disconnection). Failure
      of detection was usually with ventilator bellows descending in expiration.
      Complete failure to ventilate occurred in 143 incidents, most commonly because of
      a disconnection. Disconnection was associated, in one-third of the cases, with
      interference to the anaesthetic circuit by a third party and in nearly half with
      surgery on the head and neck. Leaks affected ventilation in 129 incidents, but in
      only 19 was ventilation totally lost; leaks associated with seal failure of the
      absorber were common. Misconnections occurred in 36 incidents, most commonly
      involving the scavenging system. The frequency of a complete failure to check an
      anaesthetic machine was greater when an induction room was involved than when
      only the operating theatre was the site of the incident. These incidents suggest
      that meticulous checking and monitoring for failure of ventilation, preferably
      using at least two separate, self-activating systems is highly desirable. The
      Australian and New Zealand College of Anaesthetists' policy on low circuit
      pressure alarms, oximetry and capnography is vindicated by these reports.

PMID- 8273886
TI  - The Australian Incident Monitoring Study. Clinical anaphylaxis: an analysis of
      2000 incident reports.
AB  - There were 57 reports of possible allergic reactions in the perioperative period
      in the first 2000 incidents reported to the Australian Incident Monitoring Study.
      These were examined and classified with respect to presentation, clinical course,
      agents implicated and management strategies employed. Reactions were graded as to
      probability of allergic aetiology and severity of systemic disturbance. Two
      deaths were reported. A method of determining an "allergy score" was devised as
      an indication of which reactions may be most deserving of further investigation.

PMID- 8273887
TI  - The Australian Incident Monitoring Study. Cardiac arrest--an analysis of 2000
      incident reports.
AB  - Eighty-seven cases of cardiac arrest from the first 2000 incidents reported to
      the Australian Incident Monitoring Study were reviewed. "Cardiac arrest" was
      taken to include patients who were either pulseless or had electrocardiographic
      asystole or ventricular fibrillation. Cases were grouped by primary cause--drug
      administration (19), vagal stimulation (16), hypoventilation (15), bleeding (13),
      anaphylaxis (6), direct cardiac stimulation (4) and miscellaneous (14). Overall,
      20 patients died (23% of the 87 cases); all of these were in the hypoventilation,
      bleeding, or miscellaneous groups (4, 9 and 7 patients, respectively). Cardiac
      compression was performed in 66% of patients; 20% were defibrillated; adrenaline
      was given to 42% and bicarbonate to 3%. There was a clear anaesthetic cause for
      46% of this series of arrests, and with hindsight, a preventable factor was
      present in over half (58%) of these. Preventative strategies regarding staffing,
      equipment, policy and procedures are suggested.

PMID- 8273888
TI  - The Australian Incident Monitoring Study. Air embolism--an analysis of 2000
      incident reports.
AB  - There were 19 cases of air embolism (1%) among the first 2000 incidents reported
      to the Australian Incident Monitoring Study. No embolism-induced fatalities were
      reported. Serious acute systemic effects occurred in 14 incidents; one
      circulatory arrest required electrical counter-shock. The surgical field was the
      entry route for the air in 63% of the incidents; 47% of the cases occurred during
      head and neck surgery. Capnography was the most successful first detector (26%)
      and it confirmed the diagnosis in another 26%. Invasive blood pressure
      monitoring, the electrocardiograph and the pulse oximeter played a useful role in
      detecting and/or confirming air embolism. Doppler monitoring was not reported in
      this series. A successful first response for management included head-down
      posture, manual ventilation, 100% oxygen and control of the air entry site.
      Cerebral arterial gas embolism may induce vascular endothelial damage and
      possible delayed neurological sequelae; hyperbaric oxygen therapy should be
      considered.

PMID- 8273889
TI  - The Australian Incident Monitoring Study. Pneumothorax: an analysis of 2000
      incident reports.
AB  - Eighteen (1%) of the first 2000 incidents reported to the Australian Incident
      Monitoring Study (AIMS) involved actual or suspected pneumothoraces; 17 were
      confirmed. Eleven of the patients were seriously ill beforehand. Four developed
      tension pneumothoraces, and in 2 incidents (1 tension) the pneumothoraces were
      bilateral. Nine of the 17 were iatrogenic; 6 (35%) followed neck vein
      cannulation, and 3 (18%) were surgical complications of tracheotomies. No death
      was attributed to a pneumothorax. In 8 of the 17 incidents, diagnostic delay or
      difficulties occurred. Contributing factors identified included urgency,
      distorted anatomy, failure to check, and haste on the part of the anaesthetist.
      Desaturation detected by pulse oximetry and hypotension detected by invasive
      blood pressure monitoring warned the anaesthetist on 2 occasions each.
      Indications for central vein cannulation or trans-tracheal airway manoeuvres must
      be firm. Such procedures should always be followed by a closely scrutinised erect
      chest X-ray as soon as practicable. The possibility of a pneumothorax must always
      be considered when unexpected cardiorespiratory deterioration occurs.

PMID- 8273890
TI  - The Australian Incident Monitoring Study. Problems with regional anaesthesia: an
      analysis of 2000 incident reports.
AB  - There were 160 incidents associated with regional anaesthesia amongst the first
      2000 incidents reported to the Australian Incident Monitoring Study. They were
      categorised into 6 groups; epidural anaesthesia (83), spinal anaesthesia (42),
      brachial plexus blocks (14), intravenous local anaesthesia (4), ocular blocks
      (3), and local infiltration (14). The largest single cause of incidents involved
      circulatory problems; these occurred in all the groups except brachial plexus
      block (30 cases of hypotension, 7 of arrhythmias, 3 of cardiac arrest, 2 of
      hypertension and 1 of myocardial ischaemia). There were 24 drug errors, of which
      10 involved the "wrong drug" and 4 "inappropriate use". With the exception of
      these, all the remainder involved problems specific to regional anaesthesia: 26
      inadvertent dural punctures; 19 failed or inadequate blocks; 14 dural puncture
      headaches (all cured by blood patches); 10 inadvertent total or high spinal
      blocks (of which 7 required artificial ventilation); 5 blocks on the wrong side
      or in the wrong patient; 3 late hypoxic incidents and a variety of miscellaneous
      problems. Three-quarters of all incidents occurred in the presence of an
      anaesthetist and over 90% in patients of ASA Groups I-III. Rapid recognition by
      the anaesthetist prevented many potentially life threatening events, and the only
      death was as a result of surgical bleeding.

PMID- 8273891
TI  - The Australian Incident Monitoring Study. Recovery room incidents in the first
      2000 incident reports.
AB  - Of the first 2000 incidents reported to the Australian Incident Monitoring Study
      120 (6%) occurred in the recovery room after general, regional or local
      anaesthesia. Over two thirds (69%) of these involved the respiratory system, 19%
      were cardiovascular, 3% involved the central nervous system and 9% were
      miscellaneous in nature. These recovery room incidents were associated with
      significantly more adverse outcomes (56%) than incidents in the operating theatre
      (24%). The types and relative frequencies of these recovery room incidents were
      similar to those of serious recovery complications in a recent analysis of closed
      malpractice claims; this suggests that incident monitoring may be useful in the
      study and prevention of recovery room complications. Over three quarters (77%) of
      all recovery incidents (and 88% of respiratory incidents) were detected
      clinically; the remainder were first detected by a monitor. A theoretical
      analysis showed that over 95% of respiratory events, had they been allowed to
      evolve, would have been detected by pulse oximetry before organ damage occurred,
      emphasising the potential importance of pulse oximetry in reducing adverse
      outcome from any complication in the recovery ward which might be "missed" by
      clinical observation. The findings of this study underline the importance of
      having an adequate number of trained recovery nursing staff supported by the
      availability of a pulse oximeter for each patient at least until the return of
      protective reflexes and the ability to maintain adequate arterial saturation has
      been established.

PMID- 8273892
TI  - The Australian Incident Monitoring Study. Patient awareness during anaesthesia:
      an analysis of 2000 incident reports.
AB  - Amongst the first 2000 incidents reported to the Australian Incident Monitoring
      Study were 16 cases in which patient recall of perioperative events was
      consistent with awareness. Awareness that occurred in 3 of 10 cases during
      anaesthesia was attributed to low concentrations of volatile anaesthetic agent;
      the conduct of anaesthesia appeared to be unremarkable in the other 7. The
      remaining 6 cases involved the inadvertent paralysis of patients prior to
      induction of anaesthesia, most commonly by "syringe swap" when suxamethonium was
      given instead of fentanyl. Some of these patients were significantly distressed.
      These preliminary findings suggest that incident monitoring should be useful in
      the study of awareness associated with anaesthesia and the development of
      strategies to prevent it.

PMID- 8273893
TI  - The Australian Incident Monitoring Study. Paediatric incidents in anaesthesia: an
      analysis of 2000 incident reports.
AB  - The first 2000 incidents reported to the Australian Incident Monitoring Study
      (AIMS) were analysed to compare anaesthetic incidents in infants and children
      with those in adults. Of the 2000, 1790 (90%) involved adults, 151 (7%) children
      and 56 (3%) infants. Healthy children (ASA I) generated a greater proportion of
      incidents in this group than adults and infants, emphasizing the need for
      maintaining the same standards for children in this group as for infants and
      higher risk groups. The AIMS results are similar to those of the United States
      (US) paediatric "closed claims" studies; the paediatric subset in both the US
      study and AIMS made up 10% of the total. Also, in both studies, incidents
      involving the respiratory and breathing circuit systems accounted for nearly half
      the problems, and cardiovascular problems and problems with the anaesthetic
      machine each accounted for 10-14% of incidents. In the AIMS study procedures on
      the head and neck yielded proportionately more incidents in the infant/child
      group than in the adult group, as did incidents involving the respiratory and
      breathing circuit systems. Incidents in the child group were often detected
      clinically; however, there were no differences between the three age groups in
      the way monitors were used or performed; hence the same monitoring
      recommendations apply to all groups. Combined oximetry and capnography would have
      detected nearly 90% of all applicable problems in the AIMS study and could have
      prevented nearly 90% of the claims arising from inadequate ventilation in the US
      "closed claims" study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273894
TI  - The Australian Incident Monitoring Study. Physical injuries and environmental
      safety in anaesthesia: an analysis of 2000 incident reports.
AB  - Of the first 2000 incidents reported to the Australian Incident Monitoring Study,
      56 (3%) involved environmental hazards or injuries to patients or staff. There
      were 17 cases of oral trauma (14 of tooth loss or damage, in 7 of which poor
      dentition played a role), 10 incidents involving problems with the operating
      table, 6 cases of skin or eye damage and 6 cases in which an electrical hazard
      was identified. Five incidents occurred during transport, and there were 4 cases
      of monitor induced trauma, 4 "needlestick" injuries and 4 miscellaneous
      incidents. Recommendations are made for trying to avoid or reduce the incidence
      of some of these problems.

PMID- 8273895
TI  - The Australian Incident Monitoring Study. Problems associated with vascular
      access: an analysis of 2000 incident reports.
AB  - There were 65 incidents involving access to the vascular system amongst the first
      2000 reported to the Australian Incident Monitoring Study. Thirty-three involved
      peripheral venous access (14 cases of extravascular extravasation, 8 of
      unintended arterial cannulation, 6 of disruptions to intravenous lines, and 5 of
      problems with infusion lines, taps, pumps and connectors). Eighteen cases
      involved central venous access (9 cases of arterial puncture with haematomas, 5
      with morbidity and/or prolonged admission), 5 of catheter misplacement and pneumo
      or hydro-thorax and 4 of problems arising from operator inexperience. Thirteen
      cases involved peripheral arterial access (5 involved equipment problems (3 with
      possible air embolism), 3 of mistaking an arterial for a venous line (drugs were
      injected in 2), 3 of losing arterial lines or signals, and 2 in which the
      presence of an arterial line placed the patient at risk). The anaesthetist should
      always question the continued integrity of any vascular access system, even when
      it has recently been shown to be functioning, and the possibility of later
      "migration" and misplacement should always be borne in mind. Whenever possible,
      correct placement of the tip should be checked (e.g. by visual inspection of the
      site, use of test doses, aspiration of blood, pressure measurement, X-rays). When
      there is more than one line, all lines and sites of access (e.g. 3-way taps)
      should be clearly labelled and checked before anything is injected or infused.

PMID- 8273896
TI  - Evaluation of safety procedures in anaesthesia and intensive care.
AB  - A study was conducted to determine the ability of junior anaesthetists to check
      the anaesthetic machine, demonstrate a knowledge of a multifunction monitor and a
      defibrillator, and know the hospital fire drill. The subjects were 38 junior
      anaesthetists working in a large multi-disciplinary teaching hospital. 45% were
      able to check the anaesthetic machine according to the guidelines of the
      Australian and New Zealand College of Anaesthetists, and 16% had a complete
      working knowledge of the monitor. All subjects could use the defibrillator but
      only 24% could adequately solve the problem of malfunction. Only one subject had
      a working knowledge of the fire drill; excluding knowledge of the fire drill only
      3 subjects (8%) satisfactorily completed all aspects of the assessment. As a
      result of this study structured checking routines are being introduced into
      anaesthetic teaching and practice and a similar multi-center study of specialist
      anaesthetists is being planned.

PMID- 8273897
TI  - The Australian Incident Monitoring Study. Equipment failure: an analysis of 2000
      incident reports.
AB  - Of the first 2000 incidents reported to the Australian Incident Monitoring Study,
      177 (9%) were due to "pure" equipment failure according to pre-defined criteria.
      Of these 107 (60%) involved anaesthetic equipment, 42 (24%) involved monitors, 17
      (10%) other theatre equipment and 11 (6%) the gas or electricity supply. Ninety
      seven (55% of the 177) were potentially life-threatening; of these two-thirds
      would be detected by the array of monitors recommended by the Australian and New
      Zealand College of Anaesthetists and all but 9 of the remainder would be handled
      by application of the crisis management algorithm recommended elsewhere in this
      symposium. Of the 9 remaining, 2 were electrical shock, 3 overheating of a
      humidifier or blood warmer, 2 the unavailability of a spare laryngoscope and 1
      the consequence of a power failure. Meticulous adherence to the equipment
      checking and monitoring guidelines of the Australian and New Zealand College of
      Anaesthetists and application of a suitable crisis management algorithm should
      protect the patient from potentially life-threatening equipment failure in
      virtually all cases except electric shock, power failure and overheating of
      warming devices.

PMID- 8273898
TI  - The Australian Incident Monitoring Study. Human failure: an analysis of 2000
      incident reports.
AB  - Information of relevance to human failure was extracted from the first 2,000
      incidents reported to the Australian Incident Monitoring Study (AIMS). All
      reports were searched for human factors amongst the "factors contributing,"
      "factors minimising", and "suggested corrective strategies" categories, and these
      were classified according to the type of human error with which they were
      associated. In 83% of the reports elements of human error were scored by
      reporters. "Knowledge-based errors" contributed directly to about one-quarter of
      incidents; the outcome of one third of incidents was thought to have been
      minimised by prior experience or awareness of the potential problems, and in one
      fifth some strategy to improve knowledge was suggested. Correction of "rule-based
      errors" or provision of protocols or algorithms were thought, together, to have a
      potential impact on nearly half of all incidents. Failure to check equipment or
      the patient contributed to nearly one-quarter of all incidents, and inadequate
      crisis management contributed to a further 1 in 8. "Skill-based errors" (slips
      and lapses) were directly responsible for 1 in 10 of all incidents, and were
      thought to make an indirect contribution in up to one quarter. "Technical errors"
      were responsible for about 1 in 8 incidents. Analysing the relative contribution
      of each type of error for each type of problem allows the development of rational
      preventative strategies.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273899
TI  - The Australian Incident Monitoring Study. System failure: an analysis of 2000
      incident reports.
AB  - Although 70-80% of problems have some component of human error, its overall
      contribution to many problems may be small; studies of complex systems have
      revealed that up to 85% are primarily due to deficiencies in the lay-out and
      processes of the system. The anaesthetist has to operate in a complex system;
      many problems originate from deficiencies in this system. Information of
      relevance to system failure was extracted from the first 2000 incidents reported
      to the Australian Incident Monitoring Study (AIMS). A system-based deficiency
      directly contributed to one-quarter of problems (four-fifths if human factors are
      included), some aspect of the system minimized the adverse outcome in over half
      of all cases (four-fifths if human factors are included), and in two-thirds
      (three-quarters if human factors are included) a system-based strategy would have
      been helpful; the system was implicated in 90% of all incidents (97% if human
      factors are included). Regardless of whether or not all human error should be
      regarded as part of the "system", attempts to modify its incidence and nature
      have to emanate from the system. AIMS reporting pathways and the organizations
      involved in developing and implementing strategies to improve the system operate
      at four levels. Level I involves the use of AIMS reports by hospitals and group
      practices for audit at a local level. Level II involves AIMS participants sending
      forms to the AIMS central office; collated information is then sent back to
      contributors by newsletter. Level III involves interaction between AIMS and the
      major professional bodies and level IV interaction between AIMS, these bodies and
      a variety of national and international agencies. Over 100 topics were identified
      from the AIMS data for consideration at one or more of these levels. AIMS has the
      potential not only to play a vital practical role in the continued enhancement of
      the quality of anaesthetic practice, but also to provide a valuable resource for
      research at the increasingly important interface between human behaviour and
      complex systems.

PMID- 8273900
TI  - Towards optimal analgesia after caesarean section: comparison of epidural and
      intravenous patient-controlled opioid analgesia.
AB  - The provision of optimal analgesia after caesarean section remains a challenge as
      satisfactory pain relief must be combined with patient satisfaction, including
      the ability to care for the newborn. In a prospective study of 132 patients, we
      have compared epidural analgesia with intravenous patient-controlled analgesia
      (IVPCA) after either epidural or general anaesthesia. Different bolus doses of
      opioid (pethidine 10 mg and 20 mg) in the IVPCA group were also compared.
      Although epidural morphine provided the greatest efficacy (average pain score out
      of 10 was 1.8 v. 2.9-3.4 for the other groups), IVPCA, especially with a bolus
      dose of 20 mg, and especially after epidural anaesthesia, provided the greatest
      patient satisfaction with the least side-effects.

PMID- 8273901
TI  - Acute renal failure associated with intramuscular ketorolac.

PMID- 8273902
TI  - Anaphylactoid reaction to ranitidine in an obstetric patient.

PMID- 8273903
TI  - One-way valve and inadvertent arterial cannulation.

PMID- 8273904
TI  - Extravasation of propofol.

PMID- 8273905
TI  - Teflon bougies to assist difficult intubations.

PMID- 8273906
TI  - Air entrainment through needle-free injection ports.

PMID- 8273907
TI  - Cataract surgery and the laryngeal mask airway.

PMID- 8273908
TI  - Characterization of planar concentration gradients in a sequential-injection
      system for cell-perfusion studies.
AB  - This paper describes the characterization of a perfusion chamber that is coupled
      with a sequential-injection system and is being designed for live-cell perfusion.
      The apparatus consists of a multi-port valve, a peristaltic pump, a perfusion
      chamber and an epifluorescence microscope. The entire system is computer
      controlled and temperature regulated. The parameters discussed are the
      concentration-time profiles with regard to the volume of reagent used and the
      position of the cell in the perfusion chamber. Other parameters discussed include
      the stopped-flow compliance, reproducibility and symmetry of the concentration
      gradients formed. The system is shown to be suitable for two modes of perfusion;
      the first in which all cells are exposed to the same concentration of reagent,
      and the second in which cells are exposed to a gradient of concentrations. All
      characterization is performed with use of bulk fluorescein as a tracer, and a
      correlation is made between the bulk flow and the response within the cellular
      environment by using 5-[N-(octadecanoyl)amino]fluorescein.

PMID- 8273909
TI  - Determination of nanogram amounts of iodine in foods by radiochemical neutron
      activation analysis.
AB  - Three different neutron activation analysis methods have been developed for the
      determination of ppb levels of iodine in food samples. The methods are based on
      the separation of iodine using (i) toluene extraction followed by bismuth sulfide
      coprecipitation; (ii) bismuth sulfide coprecipitation followed by radiochemical
      purification with palladium iodide; and (iii) radiochemical isolation by bismuth
      sulfide coprecipitation. The accuracy of these methods was evaluated by analysing
      replicate samples of reference materials. The measured values of iodine in A-11
      Milk Powder, H-4 Animal Muscle and H-9 Mixed Human Diet from the International
      Atomic Energy Agency (IAEA) are statistically indistinguishable from the IAEA
      recommended values, and those for the Standard Reference Materials 1571 Orchard
      Leaves and 1577 Bovine Liver from the National Institute of Standards and
      Technology (NIST) are in good agreement with the NIST information values. The
      precision, in terms of relative standard deviation, is 5% at 50-100 ppb and 10%
      at 5-20 ppb levels of iodine. The absolute detection limits of these methods vary
      between 0.5 and 10 ng of iodine. All three methods were used to measure the
      iodine content of several food samples. The method involving bismuth sulfide
      coprecipitation followed by radiochemical purification provides the best
      detection limit and highest precision.

PMID- 8273910
TI  - Rapid screening of fish tissue for polychlorinated dibenzo-p-dioxins and
      dibenzofurans.
AB  - A rapid, simple method for screening polychlorinated dibenzo-p-dioxin and
      dibenzofuran classes in shellfish tissue at pg g-1 wet mass concentrations is
      described. The method does not require a clean room facility and is based on
      saponification followed by extraction into hexane, clean-up using gel-permeation
      chromatography and sulfuric acid treatment, and measurement using capillary gas
      chromatography-low resolution mass spectrometry with selected ion monitoring.
      Selected ion monitoring using multiple ions eliminates interferences not removed
      by clean-up or chromatography. The detector response factor is constant for
      isomers within a class, e.g., tetrachlorodibenzo-p-dioxin isomers gave a mean
      response of 0.977 +/- 0.075 area counts fg-1, but varied significantly between
      classes. Thus one isomer serves as a 'standard' for all members of its class.
      Recoveries of added polychlorinated dibenzo-p-dioxins and dibenzofurans (20-500
      pg g-1 wet mass) averaged 95.6 +/- 6.9 and 99.0 +/- 5.7%, respectively. The
      limits of detection (five times the noise level) are 20 pg g-1 tetrachlorodibenzo
      p-dioxins and dibenzofurans, 20 pg g-1 pentachlorodibenzo-p-dioxins and
      dibenzofurans, 40 pg g-1 hexachlorodibenzo-p-dioxins and dibenzofurans, 40 pg g-1
      heptachlorodibenzo-p-dioxins and dibenzofurans, and 100 pg g-1 octachlorodibenzo
      p-dioxin and dibenzofuran. Above the limits of detection, the method gave results
      for polychlorinated dibenzo-p-dioxin and dibenzofuran classes in shellfish tissue
      comparable to those obtained by gas chromatography-high resolution mass
      spectrometry.

PMID- 8273911
TI  - Characterization of trace amounts of aluminium in biological reference materials
      by electrothermal atomic absorption spectrometry.
AB  - The homogeneity of aluminium at the ppm level in a set of reference materials
      provided by Agriculture Canada was determined by electrothermal atomic absorption
      spectrometry. The materials included bran, wheat flour, gluten, whole egg powder,
      whole milk powder, meat powder, starch, cellulose, corn kernel and corn stalk.
      Reproducible values were obtained, which indicated that all of the materials
      studied can be considered to have a homogeneous distribution of aluminium between
      samples at test portion sizes of 250 mg. All of the materials, except milk, egg
      and meat, required HF in addition to HNO3 to effect complete dissolution,
      indicating the presence of mineral matter.

PMID- 8273912
TI  - Determination of mercury levels in human urine and blood by ultraviolet-visible
      spectrophotometry.
AB  - A method for the determination of mercury levels in biological samples, i.e.,
      human urine and blood, has been developed using an incomplete cubane-type sulfur
      bridged molybdenum aqua complex, Mo3S4(4+)(aq), with analysis by
      spectrophotometry. The primary advantage of the method is that when the 'complex'
      is dissolved in sulfuric acid it reacts directly with mercury, produced by the
      addition of a reducing agent to samples containing mercury(II), giving an intense
      coloration. Levels of mercury in the biological samples can be determined using
      the 'complex' dissolved in sulfuric acid. The detection limit for mercury(II) in
      urine and blood was 0.05 ppm at the wavelength of maximum absorption (lambda max
      = 556 nm).

PMID- 8273913
TI  - Biochemical characterization of the feline AB blood group system.
AB  - The biochemical nature of the feline AB blood group system was characterized by
      analysing red blood cells from homozygous (genotype A/A) and heterozygous (A/B)
      type A, type B (B/B), and type AB cats. High performance thin layer
      chromatography (HPTLC) of red cell glycolipids revealed that specific neuraminic
      acids (NA) on gangliosides, containing ceramide dihexoside (CDH) as a backbone,
      correlated with the feline AB blood group antigens. Although disialogangliosides
      predominated, mono- and trisialogangliosides were also isolated. B cats expressed
      solely N-acetyl-NA (NeuNAc) on these gangliosides. In addition to expressing N
      glycolyl-NA (NeuNGc) containing gangliosides, A red cells have gangliosides with
      only NeuNAc or mixtures of both NA. HPTLC profiles of disialogangliosides from
      homozygous and heterozygous A cats differed slightly in the quantity of
      disialogangliosides. Equal amounts of NeuNAc and NeuNGc containing
      disialogangliosides, as well as two intermediary forms, were recovered from AB
      erythrocytes. Analysing disialogangliosides from red cells belonging to 17
      genetically related cats, we consistently obtained the expected
      disialoganglioside profile, based on blood typing and pedigree information. SDS
      PAGE of red cell membrane proteins and blotting with Triticum vulgaris, a lectin
      recognizing NeuNAc, revealed glycoproteins of approximately 51, 53, and 80 kD in
      B and AB cats but only a faint band of approximately 53 kD in A cats. By
      haemagglutination, Triticum vulgaris could also distinguish different blood types
      by specifically binding to B and AB cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273914
TI  - A novel molecular fingerprint probe based on the endogenous avian retroviral
      element (EAV) of chickens.
AB  - We have developed a novel molecular probe that is useful for DNA fingerprint
      analysis in chickens. The probe is based on the middle-repetitive, chicken
      endogenous retroviral (EAV) element. It consists of 1503 bp of the 3' portion of
      the EAV element, extending from the down-stream end of the envelope gene to the
      beginning of the downstream long terminal repeat (LTR). Unlike other probes that
      are currently in use for fingerprint analysis with chicken DNA, the EAV-based
      probe works well at normal levels of stringency, and with standard hybridization
      buffers. Digestion of chicken genomic DNA with a variety of restriction enzymes
      routinely yields up to 30 resolvable bands per bird in the 500 bp to 20 kbp
      range. In order to test the efficacy of the EAV-based fingerprint probe, we have
      used it to estimate the degree of inbreeding in the inbred WG strain of White
      Leghorns. We find that the estimates derived with the EAV probe are very similar
      to those reported previously for the WG strain. These results suggest that
      molecular probes based on endogenous retroviruses and other middle-repetitive DNA
      elements should be useful for fingerprint analysis in chickens, and in
      vertebrates in general.

PMID- 8273915
TI  - Mapping of MYF5, C1R, MYHL, TPI1, IAPP, A2MR and RNR onto sheep chromosome 3q.
AB  - Five new loci, myogenic factor 5 (MYF5), complement 1 receptor (CIR), myosin-like
      heavy chain (MYHL), islet amyloid polypeptide (IAPP), and alpha-2-macroglobulin
      receptor (A2MR), were mapped onto sheep chromosome 3q by Southern hybridization
      to a panel of chromosomally characterized sheep x hamster cell hybrid lines. The
      location of the triose phosphate isomerase (TPI1) gene and one of the nucleolar
      organizer regions (RNR) on sheep 3q was confirmed by Southern analysis. This
      study provides further evidence for the existence of a large conserved
      chromosomal segment comprising much of sheep chromosome 3q, cattle chromosome 5,
      and human chromosome 12. The distal evolutionary breakpoint on human chromosome
      12, producing the chromosomal segment U23 in cattle marked by aldehyde
      dehydrogenase (ALDH2), also produces a separate segment in sheep. Neither ALDH2
      nor pancreatic lipase (PLA2), which is also distally located on human chromosome
      12, were mapped onto sheep chromosome 3q.

PMID- 8273916
TI  - 1D-IEF analysis of BoLA class I expression using allo-antisera reveals additional
      complexity.
AB  - The use of the bovine allo-antisera in lymphocyte microcytotoxicity assays
      suggests that there is a single highly polymorphic class I product expressed by
      the BoLA system encoded by one locus. In contrast, biochemical techniques, such
      as 1D-IEF, reveal a complex pattern of bands for BoLA class I molecules from each
      animal. In order to understand the origins of this heterogeneity bovine allo
      antisera were used in the immunoprecipitation step of 1D-IEF and the results
      compared with those from immunoprecipitation using the monoclonal antibody W6/32.
      By modifying existing protocols to include Gammabind G a range of bovine allo
      antisera were used successfully to immunoprecipitate bovine MHC class I
      molecules. The results indicate that the bovine allo-antisera do not recognize
      all molecules previously assigned to BoLA class I serotypes by 1D-IEF.
      Furthermore, some of the allo-antisera immunoprecipitated molecules are not
      recognized by W6/32 and vice versa. This suggests that more than one polymorphic
      locus is expressed from the bovine MHC and that each allo-antiserum recognizes
      molecules encoded by different loci. Examination of the results also suggests the
      existence of linkage disequilibrium in the BoLA class I region.

PMID- 8273917
TI  - Equine plasminogen polymorphism: allelic frequencies in 23 breeds.
AB  - A modified procedure for detection of the two alleles of equine plasminogen using
      Western blotting methods following polyacrylamide gel isoelectric focusing is
      described. Gene frequencies in 23 breeds and Equus przewalskii are provided.

PMID- 8273918
TI  - Genetic polymorphism of transferrin (TF) and the haemoglobin alpha chain (HBA) in
      the brown hare (Lepus europaeus).
AB  - Genetic polymorphism in transferrin (TF) and in the haemoglobin alpha chain (HBA)
      was detected in the brown hare (Lepus europaeus) from Austria and Czechoslovakia
      by means of horizontal agarose and starch gel electrophoresis, respectively.
      Genetic analyses of complete families suggest that the TF and the HBA systems are
      each controlled by one autosomal gene locus with two codominant alleles. The
      distribution of both polymorphisms among some free-ranging Austrian brown hare
      populations was examined and the observed genotypes were in good agreement with
      the Hardy-Weinberg expectations. A comparison between the brown hare and the
      rabbit revealed no bands in common. The HB beta-chain was monomorphic in all
      specimens investigated.

PMID- 8273919
TI  - Highly polymorphic microsatellite markers in poultry.
AB  - Microsatellite markers have been established for a large number of species, but
      up till now very few polymorphic microsatellite markers have been reported in
      poultry. We have isolated 34 polymorphic chicken microsatellite markers of the
      poly(TG) type. The number of repeats varied from 9 up to 33. Often, other repeats
      such as poly(T) or poly (GAA) were present adjacent to the poly (TG) repeat.
      Polymerase chain reaction amplification of the microsatellites resulted in
      detection of three or more alleles in a test panel of five different animals for
      75% of the microsatellites. Segregation of five microsatellite markers has been
      tested in a small family.

PMID- 8273920
TI  - A new lipoprotein allotype Lpr3 and allele Lpr1,3 in the pig.
AB  - Specific alloprecipitins were found in blood plasma of pigs, immunized by sera of
      Lpr1 positive donors. These precipitins detected a new allotype of the
      lipoprotein Lpr system which was designated Lpr3. Genetic studies confirmed its
      codominant inheritance and subgroup character. This linear subgroup of allotype
      Lpr1 is controlled by the allele Lpr1,3. Investigations in populations of 14 pig
      breeds showed significant interbreed differences in the frequencies of alleles
      Lpr1, Lpr2 and Lpr1,3.

PMID- 8273921
TI  - [Jean-Marie Picard (1925-1992)].

PMID- 8273922
TI  - [Peroperative perfusion of fentanyl or sufentanil: plasma concentrations and
      postoperative respiratory changes].
AB  - This study was designed to assess postoperatively the time course of respiratory
      depression due to fentanyl (F) or sufentanil (S), as well as the plasma
      concentrations. Seventy patients scheduled for orthopaedic surgery lasting more
      than 3 hours were randomly assigned to two groups, F (n = 8) or S (n = 9).
      Anaesthesia was induced with etomidate (0.3 mg.kg-1), droperidol (0.15 mg.kg-1),
      vercuronium (0.1 mg.kg-1), a loading dose of either F (10 micrograms.kg-1) or S
      (1 microgram.kg-1), and maintained with 60% nitrous oxide in oxygen, and an
      infusion of F (6 micrograms.kg-1.h-1) or S (0.6 microgram.kg-1.h-1). Mechanical
      ventilation was maintained postoperatively in the recovery room until the patient
      could be extubated. PetCO2, SpO2, fR and F and S plasma concentrations were
      assessed at the end of the opioid infusion, at extubation, every hour for the
      first 6 hours, and thereafter every 2 h for a further 10 and 18 h. Time to
      extubation was the same in both groups (301 +/- 141 and 307 +/- 148 min). At the
      time, plasma concentrations of F and S were 1.35 +/- 0.9 ng.ml-1 and 0.14 +/-
      0.07 ng.ml-1 respectively. Secondary peaks in plasma concentration (78% mean
      increase in comparison to the previous figure) were observed in 6 patients in
      group F. No similar peaks occurred in group S. Mean elimination half-life was
      shorter with sufentanil (457 +/- 130 min) than with fentanyl (325 +/- 132 min)
      (not significant). The results of this study suggest that sufentanil results less
      frequently in postoperative secondary peaks than fentanyl.

PMID- 8273923
TI  - [Biological changes in intra-uterine resections under glycine irrigation].
AB  - This study was carried out to assess the relations between plasma glycine
      concentrations and the biochemical changes occurring during intra-uterine
      resections (IUR) under glycine irrigation. Sixty patients with benign uterine
      conditions were included. They were all ranked ASA 1 or 2. The biological
      parameters were assessed before surgery (T0), at the end of surgery (T1) and 60
      min afterwards (T2). They included the blood count and blood concentrations of
      sodium, potassium, chloride, proteins, bicarbonates, glucose, urea nitrogen,
      creatinine and glycine. Plasma osmolarity was calculated. The irrigation of the
      uterine cavity resulted in an increase of glycine concentrations (28% of cases),
      and a decrease of sodium (22% of cases), proteins and haematocrit (32% of cases).
      Mean osmolarity remained unchanged. Blood glycine concentrations were directly
      correlated with the volume of irrigating solution, as well as with the duration
      of surgery. Protidaemia was inversely related to the blood glycine concentration.
      Multiparous patients had lower glycine concentrations than nulliparous patients.
      This was probably due to the uterine cavity being less compliant in the latter.
      On the other hand, there was no correlation with the uterine pathological
      condition. In this series, five cases of uterine perforation occurred with very
      large biological variations, especially a decrease in haematocrit and osmolarity.
      In these cases a clinical and biological water intoxication syndrome may occur as
      a result of large volumes of irrigating fluid passing into the peritoneal cavity.

PMID- 8273924
TI  - [Comparison of hemodynamic effects of the laryngeal mask and the orotracheal
      tube].
AB  - This prospective study was designed to compare the haemodynamic response to
      insertion of either a laryngeal mask or an orotracheal tube. Twenty patients
      scheduled for orthopaedic surgery were randomly assigned to two groups :
      laryngeal mask group (n = 10) and orotracheal tube group (n = 10). Patients were
      premedicated with flunitrazepam (1 mg i.m.) and anaesthesia was induced with
      propofol (bolus of 2.5 mg.kg-1, followed by a continuous infusion of 10 mg.kg-1.h
      1) and vecuronium (0.1 mg.kg-1). Heart rate and mean arterial pressure were
      assessed non-invasively before and after induction of anaesthesia and immediately
      after tube or laryngeal mask insertion. Orotracheal intubation elicited a
      significant increase in heart rate (92 +/- 16 vs 77 +/- 19 b.min-1, p < 0.05) and
      in mean arterial pressure (117 +/- 21 vs 85 +/- 16 mmHg, p < 0.05), whereas there
      was significant increase in heart rate (74 +/- 11 vs 72 +/- 12 b.min-1) and mean
      arterial pressure (86 +/- 8 vs 81 +/- 10 mmHg) after insertion of the laryngeal
      mask. In both groups, plasma catecholamine concentrations were not significantly
      modified after tube or laryngeal mask insertion. It is concluded that, under
      propofol anaesthesia, laryngeal mask insertion does not induce any significant
      haemodynamic response in ASA 1 patients. In the opposite, orotracheal intubation
      increases both heart rate and mean arterial pressure.

PMID- 8273925
TI  - [Block of spermatic cord in surgery of the testis].
AB  - This study analyses 25 cases of spermatic cord blockade for scrotal surgery
      (hydrocele, spermatocele, tumor of epididymis). The spermatic cord was
      infiltrated, after identification of the pubic tubercle, with a mean total dose
      of 17 +/- 3 ml of a 2% lidocaine solution not containing adrenaline. The scrotal
      skin was infiltrated separately at the site of incision. Analgesia was excellent
      in 22 patients. The duration of analgesia was 82 +/- 33 min. No adverse effects
      occurred. It is concluded that the blockade of the spermatic cord is a convenient
      anaesthesia technique for testicular surgery.

PMID- 8273926
TI  - [Invasive aspergillosis in surgical intensive care patients].
AB  - Aspergillosis is a rare event in intensive care patients. Three cases of invasive
      aspergillosis due to Aspergillus fumigatus were diagnosed in a surgical critical
      care unit. Risk factors for aspergillosis were found in two liver transplanted
      patients. One of them had a primitive cutaneous aspergillosis, and the other,
      treatment difficulties due to the unavailability of an injectable preparation of
      itraconazole, a new triazole antifungal agent efficient against Aspergillus
      species. The third case occurred in a patient who had had surgery for gastric
      carcinoma with liver metastasis. The mycological examination of the air and
      workbench in the patients' rooms disclosed between 2 and 13 CFU.mm-3 of different
      Aspergillus species. Plasma itraconazole concentrations were measured in one
      patient only. They were below the therapeutic range, probably because of
      intestinal disturbances. The oral administration of itraconazole capsules through
      gastro-intestinal feeding tubes results in a poor availability of the drug. Such
      a technique of administration should therefore be undertaken with larger doses
      than those commonly recommended. Moreover, itraconazole plasma concentrations
      should be monitored. The association with amphotericin B is recommended until
      normal intestinal absorption has been obtained.

PMID- 8273927
TI  - [Anesthesia for surgery of degenerative and abnormal cervical spine].
AB  - A feature common to all congenital or inflammatory abnormalities of the cervical
      spine is an actual or potential reduction in the lumen of the spinal canal. The
      spinal cord and nerve roots are at risk. During intubation, and positioning the
      patient on the table, all untoward movements of the cervical spine may lead to
      spinal cord compression. Abnormalities of the cervical spine carry the risk of a
      difficult intubation. If there is much debate as to what constitutes optimum
      management of the airway, there is no evidence that any one method is the best.
      Recognizing the possible instability and intubating with care, are probably much
      more important in preserving neurological function than any particular mode of
      intubation. During maintenance of anaesthesia, the main goal is to preserve
      adequate spinal cord perfusion in order to prevent further damage. Spinal cord
      blood flow seems to be regulated by the same factors as cerebral blood flow.
      Hypercapnia increases cord blood flow while hypocapnia decreases it. Therefore,
      normocapnia or mild hypocapnia is recommended. Induced hypotension is frequently
      used to decrease blood loss. However, in patients with a marginally perfused
      spinal cord, the reduction in blood flow may cause ischaemia of the spinal cord
      and may therefore be relatively contraindicated. In addition to standard
      intraoperative monitoring, spinal cord monitoring is almost mandatory. Monitoring
      somatosensory evoked potentials is used routinely. However, the major limitation
      is that this technique only monitors dorsal column function; theoretically, motor
      paralysis can occur despite a lack of change in recorded signals. Neurogenic
      motor evoked potentials may now be used to monitor anterior spinal cord
      integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273928
TI  - [Continuous monitoring of mixed venous blood oxygen saturation].
AB  - Mixed venous oxygen saturation (SvO2), measured on pulmonary artery blood, is a
      convenient indicator of matching between O2 transport (TaO2) and O2 body
      consumption (VO2). The measurement technique is based on the haemoglobin
      reflection spectrophotometry principle using two or three wave lengths. The Fick
      principle points out that SvO2 depends on five parameters: SvO2 = SaO2 - (VO2/CI
      x Hb x PO) where SaO2, CI and PO respectively represent arterial O2 saturation,
      cardiac index and O2 affinity. SvO2 does not always reflect tissue O2 tension:
      when considering a given value of SvO2, PvO2 will depend upon the position of the
      oxyhaemoglobin dissociation curve. It is impossible to establish in the absolute
      a "normal" value of SvO2. However, in most clinical circumstances, an SvO2
      ranging from 60 to 80% attests that O2 tissue delivery is appropriate. Under
      certain conditions a continuous monitoring of SvO2 allows to assess another index
      such as ventilation-perfusion index or the O2 tissue extraction index. Usually
      SvO2 variations are more informative than the absolute SvO2 value. However, their
      interpretation should be cautious. First and foremost, the ability of each of the
      four main SvO2 determinants to influence the SvO2 is unequal as the numerical
      ranges of variation of these determinants are very different. Moreover, the
      attribution of a variation of SvO2 to one of its determinants implies that each
      of them is independent from the others, a feature which is very rarely seen in
      clinical practice. Finally as the mathematical relationship between SvO2 and its
      determinants is linear (SaO2 and VO2), or hyperbolic (CI and Hb), the weight of
      SaO2 or VO2 is independent of their absolute value, whereas CI or Hb weights will
      depend on their value. The limits of SvO2 monitoring are linked first to the
      occurrence of an anaerobic metabolism state when TaO2 becomes too low; SvO2 then
      just provides informations on the aerobic part of the metabolism. Moreover, SvO2
      is just a global indicator for tissue O2 oxygenation status which does not give
      any indication about regional flow distribution. Therefore, SvO2 enables systemic
      imbalance supervision only. Finally, the existence of a right-to-left shunt will
      modify the SvO2 values through various mechanisms. However the SvO2 measured, in
      the pulmonary artery, remains reliable, whereas the presence of a left-to-right
      shunt will highly alter SvO2 basal value, only its time course remaining
      significant. SvO2 monitoring, element of diagnosis and monitoring, as well as a
      warning signal, has a priori specific indications poorly assessed, so far.
      (ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8273929
TI  - [Value of thallium-dipyridamole myocardial scintigraphy in coronary patients in
      non cardiac surgery].
AB  - Cardiac assessment is of particular importance in patients with documented or
      suspected coronary artery disease (CAD) as well as in all those patients
      undergoing vascular surgery. Use of dipyridamole thallium scintigraphy (DTS) in
      this population could help to detect significant coronary artery narrowing,
      together with the location and quantification of the areas of myocardium in
      jeopardy. Such information might lead to changing the surgical procedure, or to
      starting other treatment, such as coronary angioplasty or bypass graft surgery,
      thereby diminishing the morbidity and mortality associated with surgery in these
      high-risk patients. The ability of DTS to predict acute postoperative ischaemic
      events has been suggested by several studies. Various shortcomings of DTS used as
      a preoperative screening test have been pointed out in some recent papers.
      Therefore it is concluded that: 1) DTS should not be used as a routine
      preoperative test in vascular surgical patients. DTS is not accurate enough when
      used in patients without any clinical findings suggestive of CAD, 2) DTS may
      prove more useful in stratifying patients with an intermediate probability of
      developing cardiac complications. In such patients, the test will not provide a
      linear "all or nothing" result, but, when taken together with the clinical
      findings and the nature of the surgical procedure, a complex stratification, 3)
      Because of progress in the perioperative management of high-risk patients,
      positive findings on preoperative DTS may not correlate perfectly with
      perioperative cardiac events, 4) As several factors influence thallium uptake
      after dipyridamole, DTS does not have a perfect specificity, thus leading to
      order an excessive number of coronary angiographies. Some patients will be seen
      as having a false-positive DTS, 5) Preoperative screening DTS leads to cardiac
      catheterization and hence to revascularisation, independently of symtomatology.
      Further studies must be undertaken to determine whether this approach will
      improve short and long term patient survival.

PMID- 8273930
TI  - [AIDS and non Hodgkin's malignant lymphoma disclosed by massive hematemesis].
AB  - A 40-year-old man was admitted for a major haemorrhage from the upper gastro
      intestinal tract. An emergency gastrectomy was performed to control the bleeding.
      The histopathological study revealed a non-Hodgkinian lymphoma associated with an
      AIDS, which had remained unknown. The postoperative period was complicated by
      several infections. The patient died 2 1/2 months after the hematemesis. Such
      major haemorrhage from the upper gastro-intestinal tract as the presenting
      symptom of AIDS is very rare, although this has been described during the course
      of the disease. This case illustrates the importance in reminding operating
      theater staff (anaesthetists, surgeons, nurses) of the risk of viral
      contamination when treating a young patient with hematemesis and the necessity of
      wearing gloves, face masks and glasses.

PMID- 8273931
TI  - [Hyperthyroidism induced by molar pregnancy].
AB  - A case is reported of a Senegalese patient admitted for hydatiform mole. The
      serum human chorionic gonadotrophin concentration (hCG) was 900,000 UI.l-1. The
      patient was recognized to be clinically hyperthyroid with raised T4 and T3
      values, but a very low TSH concentration. After two days of beta adrenergic
      blockade and carbimazole, a suction curettage was performed under general
      anaesthesia. Propranolol was again administered 6 hours after the surgery.
      Thyroid function returned to normal level two weeks after removal of the mole,
      suggesting that hCG was responsible for the thyrotoxicosis. Serum hCG
      concentrations closely paralleled those of free thyroxine, but the correlation
      was difficult to assess because of carbimazole. Clinical thyrotoxicosis is rare
      in molar pregnancy. The diagnosis being made in semi-urgent conditions, this
      raises the question of how to obtain rapid stabilization of the disease before
      surgery.

PMID- 8273932
TI  - [Subarachnoid hematoma after spinal anesthesia and low molecular weight heparin].
AB  - A case is reported of spinal subarachnoid haematoma occurring after spinal
      anaesthesia. The patient was given prophylactic pre and postoperative low
      molecular weight heparin. On the second postoperative day, he complained of
      backache and got a partial cauda equina syndrome. Magnetic resonance imaging
      carried out on the 6th day confirmed the presence of a spinal haematoma, which
      was removed surgically. One year later, the bilateral motor palsy which had
      involved several roots, had completely regressed. It remained a severe sensory
      loss associated with a loss of sphincter control. This case highlights the role
      of predisposing factors and the importance of early diagnosis.

PMID- 8273933
TI  - [Cerebral pneumocephalus after epidural anesthesia: a rare complication?].
AB  - A case is reported of pneumoencephalus occurring after an accidental dural
      puncture during a cervical epidural puncture using the loss of resistance
      technique. Six ml of air were injected intrathecally. The patient recovered
      spontaneously within five days. This complication may occur more frequently than
      commonly admitted. It may be difficult to differentiate between headache due to
      pneumoencephalus and that by stretching of the meninges due to cerebrospinal
      fluid leakage. Only a CT scan can help to answer this question.

PMID- 8273934
TI  - [Difficult intratracheal intubation: value of combination of laryngeal mask and
      fibroscopy].

PMID- 8273935
TI  - [Traumatic dissection of the internal carotid artery. Apropos of a case
      successfully treated without surgery].

PMID- 8273937
TI  - [Limits of postoperative autotransfusion].

PMID- 8273936
TI  - [Purulent pneumococcal pericarditis].

PMID- 8273938
TI  - [Rhabdomyolysis after opiate poisoning: an often missed diagnosis].

PMID- 8273939
TI  - [Pulse oximetry in pulseless patients].

PMID- 8273940
TI  - [10th Consensus Conference on Resuscitation and Emergency Medicine. Gastric
      lavage in acute poisoning, 27 November 1992 Nimes].

PMID- 8273941
TI  - Health care cost containment: an overview of policy options.
AB  - While health care has become one of the leading policy concerns of the American
      public, cost containment has emerged as the most prominent underlying factor.
      Components of health care cost escalation include societal problems, consumer
      demand, an aging population, the technology explosion, administrative
      inefficiencies, the malpractice crisis, fraud and abuse, the lack of health
      promotion and disease prevention, the rising number of uninsured, and regulatory
      issues. The three major categories of health reform proposals, with
      characteristic cost containment features, are discussed. A comprehensive listing
      of available cost containment interventions is summarized in ten categories.

PMID- 8273942
TI  - Prototype core content for a fellowship in emergency medical services.

PMID- 8273943
TI  - Morals and mortals in the emergency department.

PMID- 8273944
TI  - Acute pyloric perforation after prolonged crack smoking.
AB  - A 28-year-old homosexual man, previously healthy, presented with an acute abdomen
      on the fifth day of his crack binge. Abdominal free air was demonstrated by
      radiographic studies. Exploratory laparotomy discovered a clean, ulcer-free,
      pyloric perforation. This unusual case underscores the possibility of a life
      threatening visceral perforation after cocaine use.

PMID- 8273945
TI  - Pneumocephalus following an epidural blood patch procedure: an unusual cause of
      severe headache.
AB  - Pneumocephalus is a rare complication of anesthetic procedures involving the
      epidural space. We report the case of a 36-year-old woman who developed a severe
      headache due to pneumocephalus that occurred during an epidural blood patching
      procedure. This report reviews the blood patch procedure and its attendant
      complications. Emergency physicians should be aware of the potential
      complications of this commonly performed procedure and include iatrogenic
      pneumocephalus in the differential diagnosis of severe headache in the proper
      clinical scenario.

PMID- 8273946
TI  - Supralevator anorectal abscess presenting as acute low back pain and sciatica.
AB  - Anorectal abscess is a suppurative process that begins in the anal glands.
      Clinical presentation is variable and depends on the direction and tissue plane
      along which the infection tracks. All cases require urgent incision and drainage.
      We report an unusual case of a supralevator abscess in a man who presented to the
      emergency department on two occasions with acute low back pain and sciatica. The
      case demonstrates the importance and difficulty of identifying the exceptional
      case among the numerous routine cases of mechanical low back pain. Attentiveness
      to atypical features should direct the clinician to a more extensive evaluation
      for serious illness. The case also illustrates that sciatica is not a diagnostic
      end-point but rather a label for a pain syndrome that encompasses a long
      differential diagnosis.

PMID- 8273947
TI  - Pacemaker-twiddler's syndrome: a rare cause of lead displacement and pacemaker
      malfunction.
AB  - Pacemaker-twiddler's syndrome is characterized by spontaneous, subconscious,
      inadvertent, or deliberate rotation of the pulse generator by the patient
      resulting in lead dislodgement and pacemaker malfunction. We present a case of
      pacemaker-twiddler's syndrome that involved an atrioventricular sequential
      pacemaker. It resulted in failure of atrial lead capture and phrenic nerve
      stimulation but without loss of ventricular lead capture. A search of the
      literature revealed only ten previous cases reported; none were in the emergency
      medicine literature, and none involved an atrioventricular sequential pacemaker.

PMID- 8273948
TI  - Intramuscular ketamine and apnea.

PMID- 8273949
TI  - Intramuscular ketamine and apnea.

PMID- 8273950
TI  - ACEP policy statement on pediatric sedation and analgesic.

PMID- 8273951
TI  - Missed MI diagnosis.

PMID- 8273952
TI  - Evaluation of ST segment elevation criteria for the prehospital
      electrocardiographic diagnosis fo acute myocardial infarction.
AB  - STUDY OBJECTIVE: To determine retrospectively the diagnostic accuracy of various
      ECG ST segment elevation criteria for the prehospital ECG diagnosis of acute
      myocardial infarction. DESIGN AND SETTING: During a six-month period, paramedics
      acquired prehospital 12-lead ECGs on adult chest pain patients. Investigators
      interpreted ECGs independently, retrospectively, and blinded to patient outcome.
      ECGs were classified as meeting or not meeting the six ST segment elevation
      criteria regardless of ECG morphology if the criteria were present in two or more
      anatomically contiguous leads: 1 mm or more ST segment elevation; 2 mm or more ST
      segment elevation; 1 mm or more ST segment elevation in the limb leads or 2 mm or
      more ST segment elevation in the precordial leads; and the first three criteria
      with the simultaneous presence of reciprocal changes. ECGs that did not meet any
      ST segment elevation criteria were classified as normal, nonspecific ST/T wave
      changes, abnormal but not ischemic, and ischemic. Hospital charts were reviewed
      for final cardiac diagnosis. TYPE OF PARTICIPANT: Four hundred twenty-eight
      stable adult prehospital chest pain patients in whom paramedics acquired
      prehospital 12-lead ECGs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of
      the 428 cases, 123 (29%) met 1 mm or more ST segment elevation criteria. Sixty
      three (51%) of these 123 patients did not have myocardial infarctions. ECG
      characteristics most frequently associated with these non-myocardial infarction
      ECGs were left bundle branch block (21%) and left ventricular hypertrophy (33%).
      The three criteria that required the presence of reciprocal changes had the
      highest positive predictive values (93% to 95%), with sensitivities ranging from
      20% to 33%. The criteria of 1 mm or more ST segment elevation with the
      simultaneous presence of reciprocal changes had a positive predictive value of
      94% and included 18 of the 21 (86%) myocardial infarction patients who had ST
      segment elevation and received thrombolytic therapy within five hours after
      hospital arrival. Of the 428 cases, 305 (71%) did not meet any ST segment
      elevation criteria and had a sensitivity of 81% and a negative predictive value
      of 49% for the absence of acute myocardial infarction. CONCLUSION: Fifty-one
      percent of patients whose prehospital 12-lead ECG met 1 mm or more ST segment
      elevation criteria had non-myocardial infarction diagnoses. ST segment elevation
      alone lacks the positive predictive value necessary for reliable prehospital
      myocardial infarction diagnosis. Inclusion of reciprocal changes in prehospital
      ECG myocardial infarction criteria improved the positive predictive value to more
      than 90% and included a significant majority (62% to 86%) of acute myocardial
      infarction patients with ST segment elevation who received thrombolytic therapy
      within five hours after hospital arrival. ST segment elevation criteria that
      include reciprocal changes identify patients who stand to benefit most from early
      interventional strategies.

PMID- 8273953
TI  - Out-of-hospital quantitative monitoring of end-tidal carbon dioxide pressure
      during CPR.
AB  - STUDY OBJECTIVE: To assess the feasibility and potential usefulness of
      quantitative measurement of end-tidal carbon dioxide pressure (PETCO2) during out
      of-hospital cardiac arrest. DESIGN: Emergency medical technician-paramedics (EMT
      Ps) were instructed in the operation of a portable battery-powered capnograph,
      the sensor for which was attached to the endotracheal tube following intubation.
      This was a preliminary pilot study limited to defining feasibility and potential
      utility in a small group of patients. SETTING: City with population of 70,745
      served by an advanced life support emergency medical services system.
      PARTICIPANTS: Initial group of four patients who experienced out-of-hospital
      cardiac arrest and who were treated by EMT-Ps trained in operation of the
      capnograph. INTERVENTIONS: As soon as possible following endotracheal intubation
      a mainstream sensor was connected to the endotracheal tube and digital and
      capnographic waveform data obtained for the remainder of the resuscitation. Data
      were stored in memory and subsequently retrieved for the entire event, with
      digital readings at eight-second intervals. RESULTS: Capnographic measurements
      were obtained immediately after endotracheal intubation in all four patients. The
      capnograph was operated without difficulty throughout the resuscitations. Changes
      in performance of chest compression or changes in cardiac rhythm were reflected
      immediately in changes in (PETCO2). Persistent excretion of carbon dioxide during
      pulselessness was observed in two patients, consistent with "pseudo
      electromechanical dissociation." CONCLUSION: These preliminary pilot observations
      confirm the feasibility of quantitative capnography during out-of-hospital
      cardiac arrest and indicate that early institution of this noninvasive procedure
      may provide insight into pathophysiologic mechanisms such as pseudo
      electromechanical dissociation and may also track changes in pulmonary blood flow
      during chest compressions or during spontaneous circulation.

PMID- 8273954
TI  - XAP--an alternative to cocaine for topical anesthesia.

PMID- 8273955
TI  - Safety of prehospital nitroglycerin.
AB  - STUDY OBJECTIVE: To define changes in vital signs and cardiac rhythm in
      prehospital patients given sublingual nitroglycerin. DESIGN: A five-month
      prospective observational study with nitroglycerin administration as the
      independent variable. SETTING: Five independent advanced life support services.
      TYPE OF PARTICIPANT: Three hundred prehospital patients who were given
      nitroglycerin by advanced life support personnel for presumed myocardial ischemia
      or congestive heart failure; excluded were those without repeat vital signs or
      ECG monitoring and those given additional medications. INTERVENTION:
      Nitroglycerin was administered by regional emergency medical services protocols
      or by the order of an on-line medical command physician. RESULTS: Four study
      patients (1.3%) had adverse effects: One became asystolic and apneic for two
      minutes, two experienced profound bradycardia with hypotension, and one became
      hypotensive while tachycardic. All recovered. The 95% confidence interval for
      adverse effects was 0.5% to 3.4%. Mean fall in systolic blood pressure for the
      other 296 patients was 14 mm Hg for one dose (confidence interval, 11 to 16 mm
      Hg) and 8 mm Hg (confidence interval, 2 to 13 mm Hg) for a second dose. Heart
      rate changed minimally with nitroglycerin administration. The blood pressure drop
      was linearly correlated with initial systolic pressure (r = -.44; P < .001) but
      not correlated with number of prior doses of nitroglycerin, initial heart rate,
      advanced life support time interval, age, or sex. CONCLUSION: Nitroglycerin seems
      to be a relatively safe advanced life support drug; however, a few patients
      experience serious adverse effects. Most of the adverse effects we observed were
      bradycardic-hypotensive reactions, which appeared to be unpredictable by
      pretreatment characteristics. Emergency personnel should have an increased
      awareness of this danger when considering the use of prehospital nitroglycerin.

PMID- 8273956
TI  - Neuromuscular blockade-assisted oral intubation versus nasotracheal intubation in
      the prehospital care of injured patients.
AB  - STUDY OBJECTIVE: To compare nasotracheal intubation (NTI) to neuromuscular
      blockade-assisted oral intubation (NMB-assisted oral intubation) in the
      prehospital care of injured patients. DESIGN: Prospective, randomized study
      conducted over 21 months. SETTING: A university hospital-sponsored helicopter
      service. PARTICIPANTS: Consecutive adult (more than 12 years old) injured
      patients at the accident scene with an initial Glasgow Coma Scale of 8 or less in
      whom the airway was not managed immediately by unrelaxed oral intubation or
      cricothyrotomy. Subjects were randomized by 24-hour time blocks into NTI or NMB
      assisted oral intubation treatment groups. Forty-four were entered into the NTI
      group (39 randomized, two crossed over to NMB-assisted oral intubation), and 33
      were entered into the NMB-assisted oral intubation group (38 randomized, seven
      crossed over to NTI). INTERVENTIONS: NMB-assisted oral intubation
      (succinylcholine 1.5 mg/kg IV) or NTI was carried out according to standard
      protocols. RESULTS: The success rate for NTI was 79.5% (35 of 44) and was similar
      to that of NMB-assisted oral intubation, 75.8% (25 of 33; chi 2 = .16; P = .69).
      There were no significant differences between the NTI and the NMB-assisted oral
      intubation groups with regard to sex, age, outcome, and Glasgow Coma Scale. For
      those patients in whom the initial technique was successful, NTI was
      significantly quicker than NMB-assisted oral intubation (mean time of NTI, 2.9
      minutes; mean time of NMB-assisted oral intubation, 5.9 minutes; Mann-Whitney U,
      168.0; P < .01). CONCLUSION: In the prehospital management of severely injured
      patients, there is no significant difference between NMB-assisted oral intubation
      and NTI in the rate at which endotracheal intubation is achieved. However,
      practitioners may prefer NTI because it requires significantly less time to
      perform than NMB-assisted oral intubation.

PMID- 8273957
TI  - No place to unload: a preliminary analysis of the prevalence, risk factors, and
      consequences of ambulance diversion.
AB  - STUDY OBJECTIVE: To study the prevalence, risk factors, and consequences of
      ambulance diversion. DESIGN: Observational cohort analysis from January 1, 1986,
      to December 31, 1989. SETTING: Population-based study of a large urban region
      located in Northern California. PATIENTS: Individuals transported by ambulance to
      any of 13 hospitals in the region (n = 153,167). MEASUREMENTS: Diversion defined
      as the patient not being transported to their initially intended hospital because
      the hospital was unable to accept patients because of temporary emergency
      department closure. Ambulance run time recorded by radio contact was documented
      in ambulance registry. "Transport-associated deaths" were measured as any deaths
      occurring in the field, while en route, or soon after arriving at the ED.
      RESULTS: During the four-year interval, total diversions increased by 453% (n =
      718 in 1986 versus 3,973 in 1989; P < .005), thereby affecting one in nine
      transports during the last quarter of 1989. Diversion was more common in elderly
      patients (odds ratio, 1.17; 95% confidence interval, 1.11, 1.23), during the
      winter (odds ratio, 1.36; 95% confidence interval, 1.31, 1.44), and at night
      (odds ratio, 1.30; 95% confidence interval, 12.4, 1.37). Compared with their
      nondiverted counterparts, diverted transports had longer times at the scene (13.5
      versus 12.4 minutes; P < .005) and greater transport times (13.3 versus 11.6
      minutes; P < .005). We did not find a significant increase in the rate of
      transport-associated deaths (0.460 deaths per 1,000 population in 1986 versus
      0.464 deaths per 1,000 population in 1989; P = NS). CONCLUSION: Ambulance
      diversion is a common and increasing event that delays emergency medical care.

PMID- 8273958
TI  - The effect of spinal immobilization on healthy volunteers.
AB  - STUDY OBJECTIVE: To determine the effects of standard spinal immobilization on a
      group of healthy volunteers with respect to induced pain and discomfort. DESIGN:
      Prospective study. SETTING: University teaching hospital. TYPE OF PARTICIPANTS:
      Twenty-one healthy volunteers with no history of back disease. INTERVENTIONS:
      Subjects were placed in standard backboard immobilization for a 30-minute period.
      Number and severity of immediate and delayed symptoms were determined.
      MEASUREMENTS AND MAIN RESULTS: One hundred percent of subjects developed pain
      within the immediate observation period. Occipital headache and sacral, lumbar,
      and mandibular pain were the most frequent symptoms. Fifty-five percent of
      subjects graded their symptoms as moderate to severe. Twenty-nine percent of
      subjects developed additional symptoms over the next 48 hours. CONCLUSION:
      Standard spinal immobilization may be a cause of pain in an otherwise healthy
      subject.

PMID- 8273959
TI  - Intraosseous infusion: success of a standardized regional training program for
      prehospital advanced life support providers.
AB  - STUDY OBJECTIVE: To evaluate a standardized training program in intraosseous (IO)
      infusion for prehospital providers. DESIGN: Prospective multicenter 24-month
      study. SETTING: IO infusions were performed by prehospital providers from eight
      advanced life support units serving 14 hospitals within nine counties.
      PARTICIPANTS: Field advanced life support providers (paramedics and registered
      nurses). INTERVENTIONS: All providers participated in a one-hour standardized
      training session and supervised hands-on simulation. Providers completed a data
      sheet on all IO infusions performed. Data sheets were collected and summarized.
      RESULTS: One hundred thirty-four prehospital providers completed the training
      session and were approved to perform the procedure. Fifteen patients requiring IO
      infusion were encountered during the study period. Thirteen (87%) had IO infusion
      completed successfully. Clinical indications included 11 patients in cardiac
      arrest, two trauma resuscitations, one seizure, and one toxic ingestion. Patient
      ages ranged from 1 to 24 months. Seven patients were initially resuscitated. Four
      survived to hospital discharge. Procedural complications included one incidence
      of local fluid extravasation and one IO line that became dislodged en route.
      There were no complications at time of discharge in the four survivors. All
      procedures were performed in less than two minutes. CONCLUSION: A one-hour
      standardized training session was successfully used to train prehospital
      providers in the procedure of IO infusion. IO infusion then was implemented into
      their clinical practice with a satisfactory success rate and few complications.

PMID- 8273960
TI  - The efficacy of an ACLS training program for resuscitation from cardiac arrest in
      a rural community.
AB  - STUDY OBJECTIVE: To determine whether an advanced cardiac life support (ACLS)
      course in a rural hospital will improve resuscitation success from cardiac
      arrest. DESIGN: A retrospective case review of all patients in cardiac arrest
      during a 13-month period before and after the institution of an ACLS training
      program. SETTING: Emergency department of a 42-bed rural, community hospital in a
      community with no prehospital advanced life support or early defibrillation.
      PARTICIPANTS: All patients in cardiac arrest were entered into the data base.
      Twenty-nine patients were included in the pre-ACLS period and 35 in the post-ACLS
      period. There were no significant differences in age, gender, initial rhythm,
      comorbid diseases, witnessed versus unwitnessed arrest, or total arrest time in
      the patients in the pre-ACLS period compared with those in the post-ACLS period.
      INTERVENTION: ACLS provider training. MAIN RESULTS: Patients in cardiac arrest
      who had ventricular fibrillation/tachycardia as their initial rhythm had
      significant improvement in resuscitation success compared with patients in
      ventricular fibrillation/tachycardia in the pre-ACLS period (six of 15 versus
      none of nine, P < .05). Out-of-hospital cardiac arrest resuscitation was more
      successful in the post-ACLS period than in the pre-ACLS period (five of 30 versus
      none of 25, P < .05). Overall, seven of 35 patients (20%) were resuscitated
      successfully in the post-ACLS period, with two patients surviving to hospital
      discharge. This was not significantly different than the two of 29 patients (7%)
      resuscitated in the pre-ACLS period, with one patient surviving to discharge.
      CONCLUSION: The institution of an ACLS-provider course in a rural community
      hospital was associated with improvement in initial resuscitation for patients
      with ventricular fibrillation/tachycardia and out-of-hospital arrest.

PMID- 8273961
TI  - Importance of emergency physicians as referral sources for academic medical
      centers. The Gallup Organization Healthcare Group.
AB  - STUDY OBJECTIVE: To identify physician referral patterns and factors involved in
      the patient referral process. DESIGN: A telephone survey conducted on a
      systematic sample of physicians who referred at least one patient a month to a
      tertiary care center. SETTING: A major southeastern tertiary care academic
      medical center. TYPE OF PARTICIPANTS: Self-identified emergency physicians,
      family physicians, general surgeons, internists, obstetrician-gynecologists, and
      pediatricians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Emergency
      physicians comprised 6% of the surveyed sample. Emergency physicians referred the
      largest number of patients each month to a tertiary care center (40 patients per
      month) compared with the other target specialists, who referred an average of 16
      patients per month (P < .05). Specialty services most often requested by
      emergency physicians were internal medicine, trauma, and cardiology. CONCLUSION:
      Emergency physicians refer more patients to academic medical centers than any
      other specialty. Academic medical centers should target emergency physicians if
      they wish to increase their patient referral base.

PMID- 8273962
TI  - A retrospective analysis of institutional review board and informed consent
      practices in EMS research.
AB  - STUDY OBJECTIVE: To assess the frequency of institutional review board (IRB)
      review and informed consent in emergency medical services (EMS) research. DESIGN:
      Two-year, retrospective review of published EMS research. MEASUREMENTS AND MAIN
      RESULTS: One hundred two studies were analyzed. Seventy-one (70%) were exempt
      from IRB review; 31 (30%) were not exempt. Seventeen nonexempt studies (55%) did
      not obtain IRB review. Eight of these did not specify a consent method; one used
      implied consent and eight used volunteers. Volunteers gave informed consent in
      one study. Of the 14 nonexempt studies with IRB approval, seven did not specify a
      consent method. Two used informed consent, one received an informed consent
      waiver, one used verbal consent, and three involved volunteers. Written parent
      permission was used once when volunteers were minors. CONCLUSION: IRB review is
      often omitted by EMS investigators. This raises ethical concerns about EMS
      research. Investigators should document their consent method or approval to use
      an informed consent waiver in their manuscripts. A consent method should be
      specified for volunteers.

PMID- 8273963
TI  - Non-normality of distribution of Glasgow Coma Scores and Revised Trauma Scores.
AB  - STUDY OBJECTIVE: Inferential and descriptive statistics continue to be used
      incorrectly when analyzing biomedical data. Glasgow Coma Score (GCS) and Revised
      Trauma Score (RTS) data have recently been described and analyzed using
      parametric statistical methods in several studies despite the ordinal nature of
      these data scales. The objective of this study was to determine whether GCS and
      RTS data are normally distributed, despite their ordinal nature. HYPOTHESIS:
      Neither GCS nor RTS data are normally distributed. DESIGN: A retrospective review
      of GCS and RTS data obtained at a medical school teaching and county hospital
      that is a Level I trauma center. PARTICIPANTS: Patients who met criteria for
      trauma team activation at the hospital. METHODS: GCS and RTS data distributions
      were compared to a standard normal distribution using the chi 2 goodness of fit
      test. RESULTS: GCS and RTS data distributions differed significantly from the
      normal distribution for all data sets examined. CONCLUSION: Parametric
      statistical descriptors and inferential methods are inappropriate for use with
      GCS and RTS data. Ordinal data should be tested for normality before statistical
      analysis with parametric statistical methods.

PMID- 8273964
TI  - Characteristics influencing career decisions of academic and nonacademic
      emergency physicians.
AB  - STUDY OBJECTIVE: To determine characteristics motivating physicians to choose
      careers in academic and nonacademic emergency medicine. DESIGN: A written survey
      of 1,017 active members of the Society for Academic Emergency medicine and of a
      random sample of 2,000 members of the American College of Emergency Physicians
      was performed. Questions were asked regarding medical school, residency, and
      fellowship training; the importance of specific factors in influencing career
      decisions; and perceived obstacles to emergency medicine research. Responses from
      nonfaculty and adjunct, clinical, and research faculty were compared using chi 2
      analysis for discrete variables and a four-group analysis of variance for
      continuous variables. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Responses were obtained from 1,203 physicians (41.3%). Those choosing academic
      careers were significantly more likely to complete a residency in emergency
      medicine or internal medicine and fellowship training in research or toxicology
      compared with nonacademic physicians. Nonfaculty and clinical faculty considered
      family obligations, leisure time, and personal income to be the most important
      factors influencing their career decisions; research faculty considered role
      models and the value of research to be most important. There was no difference in
      indebtedness among the groups. Finding time and funding, administrative
      obligations, and pressures to do clinical work were the most important obstacles
      to research productivity. CONCLUSION: Factors influencing career decisions can be
      used to plan strategies to meet the future needs of academic emergency medicine.

PMID- 8273965
TI  - Lack of uniform definitions and reporting in laboratory models of cardiac arrest:
      a review of the literature and a proposal for guidelines.
AB  - BACKGROUND: Researchers are interested in improved uniformity of definitions and
      standards of reporting data for human CPR studies, and international guidelines
      (Utstein style) have been developed. However, no guidelines exist for animal CPR
      investigations. OBJECTIVE: To assess published animal CPR studies for adequacy of
      reporting and uniformity of methods and definitions regarding such important
      factors as the interval from the onset of ventricular fibrillation to the start
      of CPR (the nonintervention interval), ventilation, chest compression, coronary
      perfusion pressure, and return of spontaneous circulation. DESIGN: A blinded
      review of the methodology described in 42 articles concerned with animal CPR
      research published during the last ten years. An article had to report cardiac
      arrest and CPR as part of the protocol and return of spontaneous circulation as
      one of the outcome variables in order to be included in this study. We excluded
      abstracts, nonresuscitation models, and human CPR studies. MEASUREMENTS AND MAIN
      RESULTS: There was wide variation in the experimental methods reported in the
      studies. The nonintervention interval ranged from 0 to 15 minutes. The majority
      of studies initiated CPR within three minutes after the onset of ventricular
      fibrillation. Twenty-two percent of studies reported tidal volume, and 18%
      reported minute ventilation. Of the 14 studies that used blood pressure or
      coronary perfusion pressure as a target for titration of chest compression force,
      12 used different target blood pressure values. We found 29 different definitions
      of return of spontaneous circulation. The duration of return of spontaneous
      circulation ranged from 30 seconds to 60 minutes; however, 52% of studies did not
      report a duration. CONCLUSION: Important differences exist in animal CPR research
      methodology among laboratories. Failure to define or report minute ventilation,
      coronary perfusion pressure, and return of spontaneous circulation made it
      difficult to compare studies. In order to make valid comparisons of studies,
      blood flow and ventilation should be measured and controlled when they are not
      experimental variables. Uniform definitions and guidelines for reporting should
      be developed for laboratory CPR research.

PMID- 8273966
TI  - Model curriculum for physician training in emergency ultrasonography.
AB  - A model curriculum for the implementation and training of physicians in emergency
      medicine ultrasonography is described. Widespread use of limited bedside
      ultrasonography by emergency physicians will improve diagnostic accuracy and
      efficiency, increase the quality of care, and prove to be a cost-effective
      technique for the practice of emergency medicine.

PMID- 8273967
TI  - The white water rapids of the 90s.

PMID- 8273968
TI  - Impact of technetium-99m-sestamibi localization on operative time and success of
      operations for primary hyperparathyroidism.
AB  - Intraoperative identification of abnormal parathyroid glands during initial neck
      exploration for primary hyperparathyroidism is challenging and may require
      extensive dissection of the neck and mediastinum. We, therefore, evaluated the
      impact of preoperative localization with Technetium-99m-sestamibi (Tc-99m
      sestamibi) and Iodine-123 radionuclide subtraction imaging on operative time and
      success of initial operation for primary hyperparathyroidism. From January 1989
      to September 1992, 42 patients underwent neck exploration for primary
      hyperparathyroidism; 21 patients underwent neck exploration without preoperative
      radionuclide scanning, and 21 patients were operated upon following radionuclide
      Tc-99m-sestamibi localization. In the control group, pathologic exam revealed 15
      patients had solitary adenomas, and six patients had diffuse hyperplasia. In the
      Tc-99m-sestamibi group, 16 patients had solitary adenomas, four had diffuse
      hyperplasia, and one had multiple adenomas. Analysis of patient demographic data
      revealed no differences between the control group and the Tc-99m-sestamibi group
      in mean age (56 vs 59 years), mean intact PTH levels (249 vs 234 pg/mL), mean
      total calcium (11.3 vs 12.0 mg/dL), and mean ionized calcium (6.19 vs 6.28
      mg/dL). Comparison of operative data revealed no differences between groups in
      the mean number of parathyroid glands identified and biopsied per patient (3.1 vs
      3.3), the mean largest diameter of the resected adenomas (19.6 vs 20.0 mm), and
      the number of patients requiring thymectomy, thyroid resection, retroesophageal
      exploration, mediastinal exploration, or carotid sheath exploration. The
      operative success rate was 90 per cent for the control group versus 100 per cent
      for the Tc-99m-sestamibi group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273969
TI  - Therapeutic manipulation of cytokines: transforming growth factor beta-1 protects
      mice treated with lethal doses of cytarabine.
AB  - We have developed a mouse model to utilize the specific regulatory effects of
      Transforming Growth Factor Beta-1 (TGF beta 1), the prototype for a family of
      growth inhibitory cytokines. A vital factor in the regulation of normal cellular
      growth for many cell types, TGF beta 1 prevents proliferation by reversibly
      arresting cells at the G1/S border of the cell cycle, thus delaying DNA synthesis
      and cell division. Since the dose of cytotoxic chemotherapy is limited by its
      adverse effects on bone marrow and gut cells, we proposed that a TGF beta 1
      induced block at G1/S would diminish the S phase toxicity of high dose cytarabine
      (ara-C). The dosage of ara-C required to kill 90 per cent of 4-week old DBA/2
      males was determined to be 3200 mg/kg every 12 hours x 2. Pretreatment with TGF
      beta 1 6-24 hours before the first dose of ara-C proved to be significantly
      protective; 8/9 TGF beta 1-pretreated mice survived versus 1/9 treated with TGF
      beta 1 for 3 hours or less or with ara-C alone (chi2 = 10.89 P = 0.001). A second
      experiment confirmed this effect; TGF beta 1 pretreatment for 6-24 hours
      protected 9/9 versus 0/9 survivors in the group treated with TGF beta 1 for 3
      hours or less or with ara-C alone (chi2 = 18.0, P < 0.001).(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8273970
TI  - Heparin-induced thrombocytopenia.
AB  - Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin with
      significant morbidity and mortality. In this study, a retrospective review of all
      patients referred to the platelet study lab at East Carolina University who
      tested positive for heparin-induced platelet aggregation was performed. From May
      1988 through March 1991, 40 patients with clinically suspected HIT were referred
      for platelet aggregation studies. Ten patients tested positive for in-vitro
      platelet aggregation in the presence of heparin. The clinical characteristics of
      these patients are reviewed. Results show a preponderance of surgical patients
      with 8/10 patients having undergone a primary major surgical procedure. Six of
      the eight surgical patients underwent a major vascular or cardiac procedure. The
      mortality rate for patients with heparin-induced in-vitro platelet aggregation
      was 30 per cent. Major thromboembolic morbidity was substantial (80%) with 5/10
      patients requiring an extremity amputation. The estimated incidence of HIT in
      surgical patients in this series was 0.3 per cent. HIT is an unusual complication
      of heparin therapy with devastating morbidity and mortality. Patients undergoing
      a major vascular or cardiac procedure appear to be at increased risk. Increased
      awareness of the syndrome and careful monitoring of platelet counts in patients
      at high risk may reduce the morbidity and mortality.

PMID- 8273971
TI  - Laparoscopic appendectomy: is it worth it?
AB  - Data on all laparoscopic appendectomies (LA) were collected prospectively from
      June 1990 through July 1992 and compared retrospectively with all open
      appendectomies (OA) done at the same hospital during the same time period.
      Laparoscopic appendectomies were performed in 29 patients (ages 15-47, mean 25.3
      years) and OA in 77 patients (ages 18-71, mean 31.9 years, P < 0.01).
      Preoperative findings were similar in the two groups. Acute appendicitis was
      confirmed in 22 (76%) LA and in 57 (74%) OA; of these, 9/22 (41%) LA and 23/57
      (40%) OA were gangrenous or perforated. A normal appendix was removed in seven
      (24%) LA and in 20 (26%) OA. Three patients (10%) required conversion of LA to an
      open procedure. Operative time was significantly longer for LA (mean 105 minutes)
      compared with OA (mean 69 minutes; P < 0.001). Postoperative complications
      requiring further intervention (wound infection or intraabdominal abscess)
      occurred in three LA (10%) and in 23 OA (30%, P < 0.05). Wound morbidity as
      measured by number of wounds left open at surgery or opened for infection was
      significantly less after LA (14% LA, 39% OA, P < 0.001). Hospital stay was
      significantly shorter after LA (mean 4.2 days) compared with OA (mean 6.3 days; P
      < 0.05). Hospital charges and professional fees were not significantly different
      between the two groups. In selected patients, LA is a safe, effective alternative
      to OA, with fewer complications and shorter hospital stay. In addition, hospital
      charges are similar, making an investment of more time in the operating yield an
      outcome equal or superior to OA.

PMID- 8273972
TI  - A prospective reappraisal of primary repair of penetrating duodenal injuries.
AB  - Based on a retrospective analysis of 100 penetrating duodenal injuries, the role
      of primary repair or resection and anastomosis was assessed prospectively in 66
      patients (1986-1992). Duodenal exclusion was reserved for extensive combined
      pancreato-duodenal injuries. Seven of the 66 patients died from extensive
      abdominal trauma (mean Abdominal Trauma Index, ATI 70) within 48 hours of
      admission. Fifty-six patients had primary repair, while pyloric exclusion was
      performed for three patients with extensive pancreatico-duodenal injuries. Three
      patients (5.1%) developed duodenal fistula, two being in the primary repair group
      (3.6%). All three patients had associated injury to the head of the pancreas.
      Four of the 59 patients died, one attributed to the duodenal repair, for a
      duodenal mortality of 1.7 per cent. Of the anatomic (ATI, duodenal, vascular, and
      pancreatic injury scores) and physiologic variables (shock, transfusions)
      analyzed, the ATI, the Duodenal Injury Score, and the Colon Injury Score were
      significantly higher in the fistula group. We conclude that the vast majority of
      penetrating duodenal injuries should be managed by primary repair or resection
      and anastomosis. Complex duodenal decompression or diverticulization rarely are
      necessary. Complex procedures should be considered for patients with ATI > 40,
      Duodenal Injury Score > 12, and the presence of injury to the head of the
      pancreas.

PMID- 8273973
TI  - Colonic complications of pancreatitis.
AB  - A retrospective review of 296 patients referred for surgical management of
      pancreatitis from 1964 to 1992 revealed that 18 (6.1%) had colonic complications.
      Of seven patients with chronic pancreatitis, six developed pancreatocolonic
      fistulas. One had stenosis of the transverse colon, which resolved after
      pancreatic cystjejunostomy, three were managed with local fistula excision and
      simple colon closure, three had segmental colectomy, and in one the fistula
      closed spontaneously with expectant management. Three patients had concomitant
      lateral pancreaticojejunostomy, and two had a cystjejunostomy. There were two
      postoperative complications, but no mortality. Eleven patients had acute
      necrotizing pancreatitis. Seven developed segmental colonic infarction that
      required partial colectomy. Four had colonic fistulas, two managed with partial
      colectomy and colostomy, and two managed nonoperatively. Eleven patients
      developed major postoperative complications; four died, two from sepsis and
      multiorgan failure and two from recurrent hemorrhage from a necrotic pancreatic
      bed. Our findings indicate that the presentation, management, and outcome of
      colonic complications differ in chronic and acute pancreatitis. In chronic
      pancreatitis, pancreatocolonic fistula predominated and could be managed either
      with local excision or segmental resection of the colon with excellent results.
      Simultaneous surgical correction of associated pancreatic pathology was possible
      in five patients. In acute necrotizing pancreatitis, colonic infarction secondary
      to the necrotizing inflammatory process was frequent and required colon
      resection. There was substantial morbidity and mortality in spite of treatment
      with colectomy.

PMID- 8273974
TI  - The mangled lower extremity: can salvage be predicted?
AB  - The ability to predict amputation following combined orthopedic, vascular and
      soft tissue trauma to an extremity could eliminate prolonged attempts at salvage
      of a doomed limb. We reviewed our experience with 48 mangled lower extremities in
      46 patients. Twenty-one penetrating wounds and 25 blunt injuries occurred in 37
      men and nine women ranging in age from 3 to 59 years. Severity of injuries to
      muscle, skin, and major nerves were strongly interrelated (r = 0.49 to 0.74, P <
      0.001), but there were no correlations between injuries to these tissues and
      severity of bone injury (r < 0.19, P > 0.20). Twenty-four limbs were salvaged,
      and 24 were amputated. Increased severity of soft tissue injury was associated
      with a greater probability of limb loss (P < 0.001), but limb salvage or
      amputation could not be predicted accurately by any variable or group of
      variables such as age, mechanism of injury, Injury Severity Score, presence of
      shock, level of injury, venous injury or repair, sequence of repair (vascular vs
      skeletal), time of fasciotomy, arteriography, blood requirement, or duration of
      ischemia. Amputation was best predicted by severity of injury to the sciatic or
      tibial nerves (P < 0.001), and by failure of arterial repair (P < 0.01). Severe
      extremity injuries require a coordinated approach and decisions regarding
      amputation require careful judgement. These decisions cannot always be made at
      the time of presentation or during the initial operation. If after
      revascularization and skeletal stabilization the extremity is clearly nonviable
      or remains insensate, then delayed amputation can be performed under more
      controlled circumstances.

PMID- 8273975
TI  - A comparison of patient charges associated with percutaneous transluminal
      coronary angioplasty and coronary artery bypass grafting.
AB  - Appropriate interventional treatment for coronary artery disease is an important
      component in controlling health care expenditures. We conducted a retrospective
      study to compare the patient charges associated with percutaneous transluminal
      coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG). All
      patients underwent treatment for left anterior descending coronary artery
      stenosis over a 3 year 9 month time period from March 1987 to December 1990 and
      were followed for 7-58 months (median 43 months) after treatment. The two groups
      were constructed in such a way that they were balanced for common vessels
      diseased, number of vessels diseased, sex, age, and ejection fraction (EF). The
      study included 26 PTCA patients between the ages of 33 and 86 years, 18 males and
      eight females, with a mean EF of 58 per cent, and 26 CABG patients from 39 to 80
      years of age, 18 males and 8 females, with a mean EF of 61 per cent. Charges were
      categorized as to hospital, professional, cardiac medication, follow-up, and
      total costs. While CABG was initially more expensive, nine of the PTCA patients
      (38%) required further interventional treatment (3 PTCA, 5 CABG, 1 PTCA and
      CABG), whereas none of the CABG patients required further intervention (P <
      .001). This short-term follow-up demonstrated, that although initially less
      expensive, repeat interventional charges are significantly higher in PTCA
      patients. With the escalating costs of health care, the appropriate initial
      interventional therapy for coronary artery disease must be carefully selected to
      reduce long-term health care expenses.

PMID- 8273976
TI  - Management of infected pancreatic fluid collections.
AB  - Percutaneous drainage of pancreatic collections has recently been advocated as a
      means of diagnosis of bacterial contamination, for temporizing unstable patients,
      and as definitive treatment in itself. In order to assess its efficacy, the role
      of percutaneous drainage of infected pancreatic fluid collections was
      retrospectively reviewed by a single surgical practice. Seventeen patients were
      treated over a 5-year period from 1987 to 1992. All patients admitted or referred
      with a diagnosis of infected peripancreatic fluid collection were included in the
      review. The group consisted of eleven males and six females; mean age was 55.2
      years (range 28 to 70). Patients were stratified into one of two groups based on
      initial treatment modality. Group A consisted of eight patients treated initially
      with percutaneous drainage as presumed definitive management. Eight patients in
      Group B were treated initially with surgical debridement and drainage. APACHE II
      scores on admission were 5.62 +/- 3.66 for Group A and 9.12 +/- 3.87 for Group B
      (N.S.). Mean hospital stay was 100 days (range 13-311) for Group A and 71 (range
      25-149) for Group B (N.S.). Despite initial percutaneous drainage, six of eight
      (75%) patients in Group A required operative debridement because of clinical
      deterioration. APACHE II scores in this subset went from 6.83 +/- 3.43 to 9.83 +/
      5.04 (N.S.) despite a total of 18 preoperative percutaneous procedures (2.25 per
      patient; range 1-7). The number of complications for this group totaled 15. Five
      of the six patients with positive cultures from their initial aspiration failed
      percutaneous drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273977
TI  - The anatomy of appendicitis.
AB  - Acute appendicitis is a common disorder and, ideally, should be diagnosed prior
      to the onset of gangrene or perforation. Nonetheless, the goal of early diagnosis
      remains elusive. In a prospective study, 100 appendectomies were performed for
      suspected acute appendicitis over 19 months. The location of the appendix was
      noted by the operating surgeon and was listed as anterior intraperitoneal,
      retrocecal, pericolic gutter, retroileal, pelvic, or retroperitoneal. The latter
      four positions were regarded as sites in which the appendix was hidden from the
      anterior parietal peritoneum. Fifteen patients did not have appendicitis. Of the
      85 inflamed appendices, 25 were indurated, 19 were suppurative, and 41 were
      gangrenous or perforated. Patients with gangrene or perforation were more likely
      to have pain and tenderness at a site other than the right lower quadrant and had
      a higher mean heart rate on admission than patients with simple appendicitis, but
      there were no other differences in symptoms, signs, or laboratory findings among
      the groups. The appendix was in a hidden location in 15 per cent of patients with
      simple appendicitis or without appendicitis, compared with 68 per cent of
      patients with gangrenous or perforative appendicitis (P < 0.001). Complications
      were more frequent, and hospital stays were longer in patients with advanced
      appendicitis (P < 0.001). Patients and physicians were equally responsible for
      delays in treatment, but the high incidence of hidden appendices in those with
      advanced appendicitis resulted in less severe symptoms and signs than expected.
      Anatomic variations in the location of the appendix are often responsible for
      delays in the diagnosis of appendicitis.

PMID- 8273978
TI  - Splenocytes from bile duct ligated rats do not elicit a normal immune response in
      the intact host.
AB  - Previous studies have shown impaired immune function in biliary obstruction, and
      our earlier investigations have demonstrated impaired response to alloantigens in
      the jaundiced rat host. The present study uses the graft versus host (GVH)
      popliteal lymph node assay to assess the ability of lymphocytes from bile duct
      ligated animals to elicit an immune response in normal rats. Female Lewis rats
      underwent bile duct ligation and transection (BDL) or sham celiotomy. A third
      group of rats served as normal controls. The animals were killed at intervals
      from 1 to 6 weeks after surgery, and spleen cell preparations were made.
      Splenocytes (5 x 10(6) from BDL, sham celiotomy, or normal control rats were
      injected into the hind footpads of LBNF1 hybrid rats. The contralateral hind
      footpads were injected with media as controls. The popliteal lymph nodes were
      removed and weighted 7 days after injection. The BDL rats were clinically
      jaundiced. GVH response was normal at 1 week and decreased at 2 weeks, remaining
      depressed through 6 weeks. Contralateral control lymph node weights were similar
      in all groups. Obstructive jaundice not only impairs host immune defense, but
      also significantly decreases splenocyte GVH capability.

PMID- 8273979
TI  - Alternative therapy for elderly patients with breast cancer.
AB  - Breast cancer treatment has undergone significant changes in concept, concurrent
      with alterations in our understanding of cancer biology and natural history.
      Within the last 10 years, oncologists have brought into question the traditional
      Halstedian concepts of the natural history of breast cancer and its appropriate
      management. The goal of treatment, once a primary cancer is detected in the
      breast, is to prevent metastasis and subsequent death of the patient. One hundred
      forty-two female patients over the age of 65 with histologically confirmed breast
      cancer were treated at Lankenau Hospital from 1982 to 1990. We treated 32 women
      over the age of 65 with quadrantectomy and tamoxifen as the sole form of therapy.
      No radiation, standard chemotherapy, nor axillary dissection was utilized. A
      cohort of 110 women of similar age, treated for breast cancer with "standard
      therapy" (total mastectomy or "segmental resection" and radiation with axillary
      nodal dissection) during the same time period, were also analyzed
      retrospectively. All segmental resections were followed by standard radiation
      doses to the ipsilateral breast and draining nodal basins with a local boost.
      Twenty-nine of 32 patients in the quad + tam group were available for follow-up 1
      to 8 years following treatment (mean 52 months). The cumulative overall survival
      was 67 per cent and disease-free survival 92 per cent. No patient developed local
      recurrence. Follow-up analysis of the 110 women treated in "standard fashion" was
      complete in 88 patients 1 to 8 years post-treatment (mean 56 months). Cumulative
      overall survival was 82 per cent and disease-free survival 83 per cent. Local
      recurrence was noted in five per cent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8273980
TI  - The identification of the caustic agent in gastric juice.

PMID- 8273981
TI  - Dose effects of aspirin on gastric prostaglandins and stomach mucosal injury.
AB  - OBJECTIVE: To determine if a dose of aspirin exists that might inhibit
      thromboxane-dependent platelet function without causing gastric mucosal injury,
      we studied the effects of a wide range of doses of aspirin (3 mg/d to 2600 mg/d)
      on gastric juice prostaglandins (PGE2 and PGF2 alpha), on serum thromboxane B2,
      and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA
      concentrations. DESIGN: A randomized, placebo-controlled study. SETTING: Research
      laboratory at a Veterans Affairs medical center. PARTICIPANTS: 16 healthy
      volunteers (5 men and 11 women). INTERVENTION: In the first part of the study,
      volunteers received placebo; aspirin, 324 mg/d; 1300 mg/d; or 2600 mg/d for 2
      days. In the second part, volunteers received placebo; aspirin, 3 mg/d; 10 mg/d;
      30 mg/d; or 81 mg/d for 8 days. MEASUREMENTS: Gastric juice PGE2 and PGF2 alpha,
      hemoglobin and DNA concentrations; gastric juice volume and acidity; and serum
      salicylate and thromboxane B2 concentrations. RESULTS: In the first part,
      significant and similar (approximately 50%) inhibition of gastric juice
      prostaglandin output was observed with daily aspirin doses of 324 to 2600 mg.
      However, a significant increase in gastric juice hemoglobin output occurred only
      with 2600 mg/d. In the second part, significant inhibition (approximately 50%) of
      gastric PGE2 output was noted at a daily aspirin dose of 30 mg. Lower aspirin
      doses did not reduce PGE2 output significantly, although these doses did
      significantly reduce serum thromboxane B2 in a dose-related manner. CONCLUSIONS:
      Aspirin can significantly reduce serum thromboxane B2 at doses of 3 mg/d or 10
      mg/d, which are significantly below the threshold dose for significant gastric
      prostaglandin inhibition and acute stomach mucosal injury.

PMID- 8273982
TI  - The booster effect in two-step tuberculin testing among young adults in Montreal.
AB  - OBJECTIVES: No consensus exists regarding the definition and interpretation of a
      significant boosting reaction after sequential tuberculin testing. The booster
      phenomenon is thought to represent remote tuberculous infection where tuberculin
      reactivity has waned, but it has also been described among persons with previous
      exposure to other mycobacteria or Bacille Calmette-Guerin (BCG) vaccine. We
      studied the factors affecting the booster phenomenon among Canadian-born young
      adults to determine the definition that would maximize sensitivity and
      specificity of a positive booster reaction in these persons. DESIGN: Point
      prevalence survey of initial tuberculin reactions and response to repeated
      tuberculin testing after 1 to 4 weeks. SETTING: Community-based study of all
      students entering health professional training programs at six post-secondary
      institutions. MEASUREMENTS: In 1989, 1990, and 1991, students completed self
      administered questionnaires, underwent two-step tuberculin testing with purified
      protein derivative-tuberculin (PPD-T), and had their childhood BCG vaccination
      status verified. In 1991, students were also tested with purified protein
      derivative-Battey (PPD-B) (for Mycobacterium intracellulare). RESULTS: Overall,
      74 students (5.2%) had positive booster reactions, which were significantly
      associated with older age (P < 0.001), larger initial tuberculin reactions (P <
      0.001), previous BCG vaccination (P < 0.001), older age when vaccinated (P <
      0.02), longer interval from vaccination to testing (P < 0.01), and sensitivity to
      PPD-B (P < 0.001). Boosting was not associated with the number of BCG
      vaccinations, sex, or risk factors for tuberculous infection. The pattern, mean,
      and mode of the frequency distributions of booster reactions among those with BCG
      vaccination and sensitivity to PPD-B were similar to those with assumed
      tuberculous infection. CONCLUSIONS: In young adults, booster reactions due to
      previous tuberculous infection are uncommon and cannot be distinguished from
      false-positive reactions due to past exposure to other mycobacteria.

PMID- 8273983
TI  - Effect of glucocorticoid replacement therapy on bone mineral density in patients
      with Addison disease.
AB  - OBJECTIVE: To study the influence of glucocorticoid replacement therapy on bone
      mineral density. DESIGN: Cross-sectional. SETTING: University hospital in the
      Netherlands. PATIENTS: 91 patients with Addison disease who had been receiving
      glucocorticoid replacement therapy for a mean of 10.6 years (range, 0.5 to 36.5
      years). MEASUREMENTS: Bone mineral density of the lumbar spine and both femoral
      necks using a dual-energy x-ray absorptiometer and basal serum concentrations of
      adrenocorticotropin, gonadal hormones, and adrenal androgens. RESULTS: Decreased
      bone mineral density (less than 2 standard deviations [SD] of the mean value of
      an age-matched reference population) was found in 10 of 31 men (32%; 95% Cl, 17%
      to 51%) and in 4 of 60 women (7%; Cl, 2% to 16%). No statistically significant
      differences were found between men and women with regard to age, duration of
      glucocorticoid substitution, or glucocorticoid dose, either in absolute
      quantities or when expressed per kilogram of body weight. However, in men with
      decreased bone mineral density, the daily hydrocortisone dose per kilogram of
      body weight (0.43 +/- 0.08 mg/kg; mean +/- SD) was significantly (P = 0.032)
      higher than in men with normal bone mineral density (0.35 +/- 0.10 mg/kg). After
      correction for possible confounding variables, a significant linear correlation
      was found between hydrocortisone dose per kilogram of body weight and bone
      mineral density of the lumbar spine in the men (regression coefficient, -0.86;
      Cl, -1.60 to -0.13; P = 0.029) but not in the women. CONCLUSIONS: Long-term
      treatment with standard replacement doses of glucocorticoids may induce bone loss
      in men with Addison disease. Adjustment of glucocorticoid therapy to the lowest
      acceptable dose is mandatory in Addison disease, and regular measurement of bone
      mineral density may be helpful in identifying men at risk for the development of
      osteoporosis.

PMID- 8273984
TI  - Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12)
AB  - OBJECTIVE: To evaluate protein-bound cyanocobalamin (vitamin B12) absorption
      before and after omeprazole (Prilosec) therapy in healthy male volunteers.
      DESIGN: Clinical trial in which each volunteer served as his own control.
      SETTING: Outpatient department of a university medical center. PARTICIPANTS: Ten
      healthy, male volunteers 22 to 50 years old. INTERVENTION: Each participant had a
      modified Schilling test (protein-bound cyanocobalamin) and a gastric analysis, as
      well as measurements of serum vitamin B12, gastrin, and folate levels. Five
      patients were then randomly assigned to take either 20 mg or 40 mg of omeprazole
      daily. After 2 weeks of omeprazole therapy, these tests were repeated.
      MEASUREMENTS: The modified Schilling test, gastric analysis, serum gastrin level,
      folate level, and cyanocobalamin level. RESULTS: At the end of the 2-week
      treatment period, cyanocobalamin absorption decreased from 3.2% to 0.9% (P =
      0.031) in participants receiving 20 mg of omeprazole daily. In patients taking 40
      mg of omeprazole daily, cyanocobalamin absorption decreased from 3.4% to 0.4% (P
      < 0.05). CONCLUSIONS: Omeprazole therapy acutely decreased cyanocobalamin
      absorption in a dose-dependent manner.

PMID- 8273985
TI  - Postpartum coma and death due to carbamoyl-phosphate synthetase I deficiency.

PMID- 8273986
TI  - Glycogen storage disease in adults.
AB  - OBJECTIVE: To identify complications amenable to prevention in adults with
      glycogen storage disease (GSD) types Ia, Ib, and III and to determine the effect
      of the disease on social factors. DESIGN: Case series and clinical review.
      SETTING: Referral medical centers in the United States and Canada. PATIENTS: All
      patients with GSD-Ia (37 patients), GSD-Ib (5 patients), and GSD-III (9 patients)
      who were 18 years of age or older. MEASUREMENTS: Ultrasound or radiographic
      studies identified liver adenomas, nephrocalcinosis, or kidney stones.
      Radiographic studies identified osteopenia. Reports of the clinical examination,
      serum chemistry results, and social data were obtained. RESULTS: For patients
      with GSD-Ia, problems included short stature (90%), hepatomegaly (100%), hepatic
      adenomas (75%), anemia (81%), proteinuria or microalbuminuria (67%), kidney
      calcifications (65%), osteopenia or fractures or both (27%), increased alkaline
      phosphatase (61%) and gamma-glutamyltransferase (93%) activities, and increased
      serum cholesterol (76%) and triglyceride (100%) levels. Hyperuricemia was
      frequent (89%). Patients with GSD-Ib had severe recurrent bacterial infections
      and gingivitis. In patients with GSD-III, 67% (6 of 9) had increased creatinine
      kinase activity. Four of these patients had myopathy and cardiomyopathy.
      CONCLUSIONS: For GSD-Ia, hyperuricemia and pyelonephritis should be treated to
      prevent nephrocalcinosis and additional renal damage. For GSD-Ib, granulocyte
      colony-stimulating factor may prevent bacterial infections. For GSD-III, more
      data are required to determine whether the myopathy and cardiomyopathy can be
      prevented. Most of the patients with GSD-I and GSD-III had 12 or more years of
      education and were either currently in school or employed.

PMID- 8273987
TI  - Nitric oxide: a physiologic messenger.
AB  - PURPOSE: To review the physiologic role of nitric oxide, an unusual messenger
      molecule that mediates blood vessel relaxation, neurotransmission, and pathogen
      suppression. DATA SOURCES: A MEDLINE search of articles published from 1987 to
      1993 that addressed nitric oxide and the enzyme that synthesizes it, nitric oxide
      synthase. STUDY SELECTION: Animal and human studies were selected from 3044
      articles to analyze the clinical importance of nitric oxide. Descriptions of the
      structure and function of nitric oxide synthase were selected to show how nitric
      oxide acts as a biological messenger molecule. DATA EXTRACTION: Biochemical and
      physiologic studies were analyzed if the same results were found by three or more
      independent observers. DATA SYNTHESIS: Two major classes of nitric oxide synthase
      enzymes produce nitric oxide. The constitutive isoforms found in endothelial
      cells and neurons release small amounts of nitric oxide for brief periods to
      signal adjacent cells, whereas the inducible isoform found in macrophages
      releases large amounts of nitric oxide continuously to eliminate bacteria and
      parasites. By diffusing into adjacent cells and binding to enzymes that contain
      iron, nitric oxide plays many important physiologic roles. It regulates blood
      pressure, transmits signals between neurons, and suppresses pathogens. Excess
      amounts, however, can damage host cells, causing neurotoxicity during strokes and
      causing the hypotension associated with sepsis. CONCLUSIONS: Nitric oxide is a
      simple molecule with many physiologic roles in the cardiovascular, neurologic,
      and immune systems. Although the general principles of nitric oxide synthesis are
      known, further research is necessary to determine what role it plays in causing
      disease.

PMID- 8273989
TI  - Flogging trolls.

PMID- 8273988
TI  - Evidence of hypertrophic osteoarthropathy in human skeletal remains from pre
      Hispanic Mesoamerica.
AB  - Hypertrophic osteoarthropathy is one of the earliest recognized disease entities
      in the history of medicine. It has a peculiar periosteal proliferation
      distinctive from other bone diseases. In its advanced stage, it leaves an
      indelible mark on the skeleton. It has been recently shown that digital clubbing
      is accompanied by a bone remodeling process of the underlying phalanges. Thus,
      theoretically, this entity can be recognized in ancient human skeletal remains.
      We studied part of the collection of skeletal remains from pre-Hispanic
      Mesoamerica preserved at the National Museum of Anthropology of Mexico City. We
      examined 1000 specimens and found 2 skeletons with widespread, bilateral,
      symmetric periosteal proliferation of the tubular bones in addition to the bone
      remodeling changes of the distal phalanges. One of the specimens was from the
      Formative period (2000 B.C. to 100 A.D.). We conclude that hypertrophic
      osteoarthropathy can be recognized in ancient human skeletal remains and that
      this disease was present in Mesoamerica near the time of the original description
      of clubbing by Hippocrates about 2500 years ago.

PMID- 8273990
TI  - Rheumatic heart disease in developing countries: the consequence of inadequate
      prevention.

PMID- 8273991
TI  - Inborn errors of metabolism: a new purview of internal medicine.

PMID- 8273992
TI  - Digoxin immune Fab therapy for digoxin toxicity.

PMID- 8273993
TI  - Controversy over multiple chemical sensitivities.

PMID- 8273994
TI  - Controversy over multiple chemical sensitivities.

PMID- 8273995
TI  - Controversy over multiple chemical sensitivities.

PMID- 8273996
TI  - Controversy over multiple chemical sensitivities.

PMID- 8273997
TI  - Controversy over multiple chemical sensitivities.

PMID- 8273998
TI  - Influence of growth conditions on production of capsular and extracellular
      polysaccharides by Rhizobium leguminosarum.
AB  - The influence of growth rate and medium composition on exopolymer production by
      Rhizobium leguminosarum was studied. When grown in medium containing 10 g/l
      mannitol and 1 g/l glutamic acid, Rhizobium leguminosarum biovar trifolii TA-1
      synthesized up to 2.0 g/l of extracellular polysaccharide (EPS), and up to 1.6
      g/l of capsular polysaccharide (CPS). Under non-growing cell conditions in medium
      without glutamic acid, CPS synthesis by strain TA-1 could proceed to 2.1 g/l,
      while EPS-production remained relatively low (0.8 g/l). Maximal CPS-yield was 2.9
      g CPS/l medium in a medium containing 20 g/l mannitol and 2 g/l glutamic acid.
      The EPS-deficient strain R. leguminosarum RBL5515, exo4::Tn5 was able to produce
      CPS to similar levels as strain TA-1, but CPS-recovery was easier because of the
      low viscosity of the medium and growth of the cells in pellets. With strain TA-1
      in nitrogen-limited continuous cultures with a constant biomass of 500 mg cell
      protein/l, EPS was the most abundant polysaccharide present at every dilution
      rate D (between 0.12 and 0.02 h-1). The production rates were 50-100 mg/g
      protein/h for EPS and 15-20 mg/g protein/h for CPS. Only low amounts of cyclic
      beta-(1,2)-glucans were excreted (10-30 mg/l) over the entire range of growth
      rates.

PMID- 8273999
TI  - Nutritional physiology and selective isolation of Exophiala dermatitidis.
AB  - The nutritional physiology of ten strains of Exophiala dermatitidis was
      investigated. The growth reactions to lactose, citrate, nitrate, nitrite, lysine,
      creatine and creatinine differ from those found in closely related black yeasts.
      In addition, it is the only Exophiala species which is able to grow at 40 degrees
      C. A selective medium containing meso-erythritol as sole carbon source was
      evaluated. This medium is particularly useful for the isolation of black yeasts
      from lungs of patients with cystic fibrosis as well as from the environment.

PMID- 8274000
TI  - Nikkomycin-resistant mutants of Mucor rouxii: physiological and biochemical
      properties.
AB  - We isolated three nikkomycin-resistant mutants of the dimorphic fungus M. rouxii
      which were physiologically characterized regarding their response to yeast-phase
      inducing conditions and their sensitivity to bacilysin. Mutant strains G21 and
      G23, showed a qualitatively normal, though delayed, dimorphic transition and
      partial cross-resistance to bacilysin. Mutant strain G27 showed an altered
      dimorphism, producing a high proportion (50%) of hyphal cells, and a wild-type
      sensitivity to bacilysin. Cell-free extracts from this mutant exhibited an
      activity of both basal and protease-activated chitin synthetase which was
      overexpressed as compared with the parental strain and mutants G21 and G23.
      Results are discussed in terms of the different genetic background of the
      mutants.

PMID- 8274001
TI  - N-terminal amino acid sequence of mutant strain Brevibacterium sp. adipamidase.
AB  - The adipamidase of a mutant strain Brevibacterium sp. R312 involved in the
      degradation of adiponitrile to adipic acid was purified. Its N-terminal amino
      acid sequence was shown to be identical to Brevibacterium sp. R312 enantio
      selective amidase and Rhodococcus sp. N-774 amidase.

PMID- 8274002
TI  - Adherence of Streptococcus gordonii HG 222 in the presence of saliva.
AB  - The influence of the presence of saliva from different salivary glands on the
      adherence of Streptococcus gordonii strain HG 222 to saliva-coated polystyrene
      surfaces was tested. In the presence of undiluted parotid saliva or diluted
      whole, submandibular and sublingual saliva the adherence of HG 222 was enhanced
      by the formation of small aggregates on the attachment surface. In the presence
      of undiluted whole, submandibular and sublingual saliva large aggregates were
      formed and the adherence to saliva-coated polystyrene surfaces was inhibited.
      Adherence in the presence of whole saliva compared to adherence in buffer was
      decreased when lower densities of bacterial suspension were used, although in
      this case in the presence of whole saliva smaller bacterial aggregates were
      formed. In conclusion, these results suggest that the presence of saliva in
      solution may both enhance and decrease the adherence of S. gordonii HG 222 to
      saliva-coated polystyrene surfaces, partly depending on the size of bacterial
      aggregates that are formed in the presence of saliva.

PMID- 8274003
TI  - Characterization of the heat shock response in Enterococcus faecalis.
AB  - We have characterized the general properties of the heat shock response of the
      Gram-positive hardy bacterium Enterococcus faecalis. The heat resistance (60
      degrees C or 62.5 degrees C, 30 min) of log phase cells of E. faecalis grown at
      37 degrees C was enhanced by exposing cells to a prior heat shock at 45 degrees C
      or 50 degrees C for 30 min. These conditioning temperatures also induced ethanol
      (22%, v/v) tolerance. The onset of thermotolerance was accompanied by the
      synthesis of a number of heat shock proteins. The most prominent bands had
      molecular weights in the range of 48 to 94kDa. By Western blot analysis two of
      them were found to be immunologically related to the well known DnaK (72kDa) and
      GroEL (63kDa) heat shock proteins of Escherichia coli. Four other proteins
      showing little or no variations after exposure to heat are related to DnaJ, GrpE
      and Lon (La) E. coli proteins and to the Bacillus subtilis sigma 43 factor.
      Ethanol (2% or 4%, v/v) treatments elicited a similar response although there was
      a weaker induction of heat shock proteins than with heat shock.

PMID- 8274004
TI  - Effect of digitonin on membrane-bound and chitosomal chitin synthetase activity
      in protoplasts from yeast cells of Candida albicans.
AB  - The effect of digitonin on chitin synthetase present in membrane (MMF) and
      cytoplasmic fractions (chitosomes) (CF) from C. albicans yeast protoplasts has
      been determined. The zymogen is preferentially, but not exclusively, solubilized
      by digitonin from MMF. Centrifugation of distinct solubilized preparations,
      containing either zymogen, in vivo active enzyme and/or trypsin activated enzyme,
      on linear sucrose gradients suggests that both zymogen and trypsin activated
      enzyme sediment slightly slower than the active enzyme, pointing out differences
      between the activation processes in vivo and in vitro or, alternatively, that
      both enzyme activities (active in vivo and zymogenic) correspond to different
      gene products. The detection of a zymogenic activity under certain conditions
      (0.5 mg ml-1 of digitonin and 64 micrograms ml-1 of trypsin) also suggests the
      existence of more than one pool of zymogenic enzyme in the MMF. Digitonin
      sensitizes the chitosomal (CF) proenzyme to trypsin: activation is enhanced by
      low digitonin concentrations in the presence of 8 micrograms ml-1 of protease,
      whereas activity strongly decreases in the presence of 64 micrograms ml-1 of
      trypsin. Digitonin does not produce zymogen activation per se in absence of
      exogenous protease. Furthermore, chitosome structure is modified into particles
      with low buoyant densities.

PMID- 8274005
TI  - Properties of polyphosphatase of Acinetobacter johnsonii 210A.
AB  - Polyphosphatase, an enzyme which hydrolyses highly polymeric polyphosphates to
      Pi, was purified 77-fold from Acinetobacter johnsonii 210A by Q-Sepharose,
      hydroxylapatite and Mono-Q column chromatography. The native molecular mass
      estimated by gel filtration and native gel electrophoresis was 55 kDa. SDS
      polyacrylamide gel electrophoresis indicated that polyphosphatase of
      Acinetobacter johnsonii 210A is a monomer. The enzyme was specific for highly
      polymeric polyphosphates and showed no activity towards pyrophosphate and organic
      phosphate esters. The enzyme was inhibited by iodoacetamide and in the presence
      of 10 mM Mg2+ by pyro- and triphosphate. The apparent Km-value for polyphosphate
      with an average chain length of 64 residues was 5.9 microM and for tetraphosphate
      1.2 mM. Polyphosphate chains were degraded to short chain polymers by a
      processive mechanism. Polyphosphatase activity was maximal in the presence of
      Mg2+ and K+.

PMID- 8274006
TI  - Purification and characterization of the E1 component of the Clostridium magnum
      acetoin dehydrogenase enzyme system.
AB  - In Clostridium magnum strain Wo Bd P1 the formation of the enzyme components of
      the acetoin dehydrogenase enzyme system E1 (acetoin:2,6-dichlorophenolindophenol
      oxidoreductase Ao:DCPIP OR), E2 (dihydrolipoamide acetyltransferase DHLTA) and E3
      (dihydrolipoamide dehydrogenase DHLDH) were induced during growth on acetoin.
      Ao:DCPIP OR was purified from acetoin-grown cells in two steps by chromatography
      on DEAE-Sephacel and on Mono Q HR. Native Ao:DCPIP OR exhibited a M(r) of
      138,000; it consisted of two different subunits of M(r) alpha 38,500 and M(r)
      beta 34,000, and it occurred most probably in a tetrameric alpha 2 beta 2
      structure. The N-terminal amino acid sequences of the alpha- and beta-subunits
      revealed homologies to the N-termini of the corresponding subunits of Ao:DCPIP OR
      from Pelobacter carbinolicus and from Alcaligenes eutrophus; furthermore, the N
      terminus of the beta-subunit exhibited homologies to the N-termini of beta
      subunits from different 2-oxo acid dehydrogenases.

PMID- 8274007
TI  - Endosomal proteolysis precedes ricin A-chain toxicity in macrophages.
AB  - Ricin A-chain is delivered into macrophages via receptor-mediated endocytosis. We
      have found that following uptake via the mannose receptor, ricin A-chain is
      rapidly cleaved by endosomal proteases. Inhibition of endosomal proteases such as
      cathepsin D and B leads to the accumulation of toxin inside the cell. Inhibition
      of cathepsin D reduces ricin A-chain cytotoxicity, while blocking cathepsin B
      enhances cytotoxicity. Similar results were obtained using fibroblasts
      transfected with the mannose receptor. Our data strongly suggest that the
      activation or membrane translocation of ricin A-chain is dependent upon the
      action of specific proteases.

PMID- 8274008
TI  - Development of surrogate substrates for juvenile hormone esterase.
AB  - Twenty-nine thioester compounds were synthesized to test their effectiveness as
      surrogate substrates for the insect enzyme, juvenile hormone esterase (JHE).
      Substrates were designed that resembled the endogenous substrate juvenile hormone
      (JH), with one common factor being a thioester instead of carboxyl ester found in
      JH. The principle of the spectrophotometric assay is based on a modification of
      Ellman's method. Characterization of the substrates showed that replacement of
      the carbon atom by a sulfur or oxygen beta to the carbonyl of the acyl group of
      the substrates resulted in an approximate five- to sixfold increase in the rate
      of hydrolysis by JHE. The specific activities of JHE, porcine liver
      carboxylesterase, and acetylcholinesterase were determined for the surrogate
      substrates. While JHE and porcine liver carboxylesterase hydrolyzed several of
      the substrates, acetylcholinesterase did not produce any detectable hydrolysis of
      the substrates. Michaelis-Menten kinetic parameters of the surrogate substrates
      when compared to a previously reported partition assay, utilizing radiolabeled
      [3H]JH III, indicated that the surrogate substrates have lower affinity as
      indicated by higher Km values but are more easily hydrolyzed (Vmax) by JHE.
      Furthermore, optimal reaction conditions for substrate hydrolysis and the
      spectrophotometric reaction were determined. In addition, first order rate
      constants for base hydrolysis and critical micelle concentrations were determined
      for several surrogate substrates. The spectrophotometric assay was also compared
      with a Vmax and research spectrophotometer, and these two instruments produced
      almost identical slopes. The relative potency of four transition state inhibitors
      of JHE was found to be similar with those of the surrogate substrates and the
      [3H]JH III substrate.

PMID- 8274009
TI  - Radioligand exchange binding cannot directly determine the dissociation constant
      (Kd) of the rat ventral prostate nuclear androgen receptor: valid Kd
      determinations require additional uptake binding data.
AB  - Radioligand exchange was examined for its ability to derive the dissociation
      constant (Kd) of the rat ventral prostate nuclear androgen receptor. In one 24-h,
      12 degrees C incubation, Scatchard plot analysis of [3H]dihydrotestosterone
      ([3H]DHT) exchange binding produced a Kd of 6.9 x 10(-9) M. Specific binding of
      [3H]DHT ranged from 114 to 758 pM, and the extrapolated value for the total
      number of binding sites (n) was 1320 pM. When aliquots from the same receptor
      pool were incubated with unlabeled DHT, and bound androgen was measured by
      radioimmunoassay, each titration point held a concentration of specifically bound
      unlabeled DHT little different from the preincubation value of bound endogenous
      ligand (1338 pM), suggesting that few, if any, unoccupied sites were created
      during the incubation. In a second radioligand exchange assay, unoccupied
      receptor sites were measured at the end of incubation. Virtually no unoccupied
      sites were found, though the range of predicted values was 124 to 383 pM (n = 425
      pM). The data, in toto, suggest that although radioactive ligand exchanges with
      bound unlabeled ligand, the dynamics of the process do not include the creation
      of unoccupied sites. Since the Kd is determined by measuring the concentrations
      of unoccupied sites, free ligand, and receptor sites bound to ligand, the absence
      of unoccupied sites suggests that radioligand exchange cannot be used to directly
      determine the Kd of the prostate nuclear androgen receptor. The numerical value
      obtained from radioligand exchange, therefore, instead of being a Kd, is very
      likely the result of a graphic plot of the increase in specific activity of bound
      radioligand as [3H]DHT is titrated to higher levels. In the last phase of the
      study a technique was developed which allows for the correct determination of the
      Kd of the rat ventral prostate nuclear androgen receptor. For the determination,
      data from an experiment measuring uptake binding into unoccupied sites were
      combined with data obtained from radioligand exchange binding. From this, the Kd
      of the receptor was calculated to be 1 x 10(-12) M.

PMID- 8274010
TI  - Identification of the major regulatory phosphorylation site in sucrose-phosphate
      synthase.
AB  - Sucrose-phosphate synthase (SPS; EC 2.4.1.14) is regulated in part by reversible
      protein phosphorylation. When dephospho-SPS is partially purified from
      illuminated spinach leaves and incubated with [gamma-32P]ATP the enzyme is
      phosphorylated by a copurifying protein kinase. In this report, 32P
      phosphopeptides from tryptic digests of in vitro phosphorylated SPS were purified
      by metal-ion affinity chromatography and reversed-phase high-performance liquid
      chromatography. Three distinct 32P-phosphopeptides were resolved. Edman
      sequencing of the major phosphopeptide (which contained > 80% of the total 32P)
      identified the amino acid sequence as Ile-Ser-Ser(P)-Val-Glu-Met-Met-Asp-Asn-Trp
      Ala-Asn-Thr-Phe-Lys. This sequence corresponds to residues 156 to 170 of the
      deduced amino acid sequence of spinach SPS [Klein, R. R., Crafts-Brandner, S. J.,
      and Salvucci, M. E. (1993) Planta 190, 498-510, and Sonnewald, U., Quick, W. P.,
      MacRae, E., Krause, K.-P., and Stitt, M. (1993) Planta 189, 174-181].
      Identification of the phosphoseryl residue was accomplished by manual Edman
      sequencing. The two other phosphopeptides, which each contained less than 10% of
      the total 32P, were not sequenced. An Escherichia coli expressed, 26-kDa fragment
      of SPS which contains the major phosphorylation site was a substrate for the
      protein kinase which copurifies with SPS. Two-dimensional peptide mapping
      analysis of this fragment showed the major phosphopeptide was present but not the
      other site(s), suggesting that other peptides are derived from a site other than
      Ser158. These results provide additional indirect evidence for the presence of
      multiple phosphorylation sites in SPS.

PMID- 8274011
TI  - cDNA cloning and characterization of a novel member of steroid-induced cytochrome
      P450 3A in rats.
AB  - A unique cDNA clone, termed cDEX, coding for dexamethasone-inducible novel rat
      cytochrome P450 was isolated and characterized. The restriction enzyme map of the
      cDEX was slightly different from the reported two CYP3A1 sequences, and several
      nucleotide substitutions were found. Compared to the CYP3A1 sequence reported as
      P450pcn1 by F. Gonzalez et al. (J. Biol. Chem. 1985, 260, 7435-7441), there were
      26 substitutions of nucleotides leading to 11 amino acid changes and a six-base
      (two amino acid)-long deletion in the open reading frame. Comparison with the
      sequence of pP450IGC2 reported by V. Ribeiro and M. C. Lechner (Arch. Biochem.
      Biophys., 1992, 293, 147-152) showed 18 nucleotide changes resulting in eight
      amino acid substitutions and the six-base-long deletion in the coding region.
      cDEX and these clones shared 97.8 and 98.4% similarity in deduced amino acid
      sequences, respectively, while only 86.3% similarity with P450pcn2 (CYP3A2). RNA
      blot hybridization analysis indicated that the mRNA corresponding to cDEX was
      mainly induced in rat liver by the administration of steroidal agents.

PMID- 8274012
TI  - Enzyme-kinetic and immunochemical characteristics of mouse cDNA-expressed,
      microsomal, and purified CYP1A1 and CYP1A2.
AB  - Kinetics of benzo[alpha]pyrene hydroxylase (AHH), 7-methoxyresorufin o
      demethylase (MROD), and 7-ethoxyresorufin o-deethylase (EROD) were estimated in
      microsomes of Hep G2 cells infected with a recombinant vaccinia virus bearing
      mouse CYP1A1 or CYP1A2 cDNAs. The kcat and Km values obtained were compared with
      those of liver microsomal and purified mouse CYP1A1 and CYP1A2. In the matter of
      AHH activity, the kcat CYP1A1/CYP1A2 ratios were 21.2, 12.3, and 1.5 for
      expressed, microsomal, and purified CYPs, respectively. As to MROD activity, the
      kcat CYP1A2/CYP1A1 ratio was 3.0 for both expressed and microsomal CYPs and was
      8.0 for purified CYPs. As regards EROD activity, the kcat CYP1A2/CYP1A1 ratios
      were 1.0, 1.1, and 6.25 for expressed, microsomal, and purified CYPs,
      respectively. Whereas furafylline displayed an isozyme-specific inhibition of
      CYP1A2-catalyzing MROD and EROD activities, alpha-naphthoflavone was an equally
      strong inhibitor of AHH activity of the CYP1A1s and MROD activities of the
      CYP1A2s. Immunodepleted polyclonal anti-CYP1A1(-A2) and anti-CYP1A2(-A1) showed
      an isozyme-specific immunoblotting and inhibition of mouse CYP1A1 and CYP1A2
      while monoclonal antibody (Mab) 1-7-1 displayed a striking difference between its
      immunoblotting and inhibitory effects. Western blot/densitometry analysis
      revealed a 4.8 times lower binding of Mab 1-7-1 to cDNA-expressed CYP1A2 than to
      CYP1A1. The results demonstrate the reliability of the vaccinia virus expression
      system for studies on the enzymology of mouse CYP1A1 and CYP1A2.

PMID- 8274013
TI  - ATP sulfurylase from higher plants: kinetic and structural characterization of
      the chloroplast and cytosol enzymes from spinach leaf.
AB  - Two forms of ATP sulfurylase were purified from spinach leaf. The major
      (chloroplast) form accounts for 85 to 90% of the total leaf activity (0.03 +/-
      0.01 adenosine-5'-phosphosulfate (APS) synthesis units x gram fresh weight-1).
      Both enzyme forms appear to be tetramers composed of 49- to 50-kDa subunits with
      the minor (cytosolic) form being slightly larger than the chloroplast form. The
      specific activities (units x milligram protein-1) of the chloroplast form at pH
      8.0, 30 degrees C, were as follows: APS synthesis, 16; molybdolysis, 229; ATP
      synthesis, 267; selenolysis, 4.1; fluorophosphate activation, 11. Kinetic
      constants for the physiological reaction were as follows: KmA = 0.046 mM, K(ia) =
      0.85 mM, KmB = 0.25 mM, KmQ = 0.37 microM, K(iq) = 64-85 nM, and KmP = 10 microM,
      where A = MgATP, B = SO4(2-), P = total PPi at 5 mM Mg2+, and Q = APS. The
      kinetic constants for molybdolysis were similar to those of the APS synthesis
      reaction. The kinetic constants of the minor (cytosol) form were similar to those
      of the major form with two exceptions: (a) The molybdolysis activity was 120
      units x milligram protein-1, yielding a Vmax (ATP synthesis)/Vmax (molybdolysis)
      ratio close to 2 (compared to about unity for the chloroplast form) and (b) KmA
      was greater (0.24 and 0.15 mM for APS synthesis and molybdolysis, respectively).
      Initial velocity measurements (made over an extended range of MgATP and SO4(2-)
      concentrations), product inhibition studies (by initial velocity methods and by
      reaction progress curve analyses), dead end inhibition studies (with monovalent
      and divalent oxyanions), and kcat/Km comparisons (for SO4(2-) and MoO4(2-)
      support a random AB-ordered PQ kinetic mechanism in which MgATP and SO4(2-) bind
      in a highly synergistic manner. Equilibrium binding studies indicated the
      presence of one APS site per subunit. HPLC elution profiles of chymotryptic and
      tryptic peptides were essentially the same for both enzyme forms. The N-terminal
      sequence of residues 5-20 of the cytosol enzyme was identical to residues 1-16 of
      the chloroplast enzyme.

PMID- 8274014
TI  - Monkey 3-deoxyglucosone reductase: tissue distribution and purification of three
      multiple forms of the kidney enzyme that are identical with dihydrodiol
      dehydrogenase, aldehyde reductase, and aldose reductase.
AB  - 3-Deoxyglucosone (3DG) is a reactive intermediate in the glucose-mediated cross
      linking of proteins. An enzyme catalyzing the reduction of 3DG is thought to
      prevent the damage to protein by the formation of 3DG. The NADPH-dependent enzyme
      activity was detected in the extracts of various monkey tissues, among which
      kidney exhibited the highest specific activity. One dimeric enzyme with subunit
      M(r) of 39,000 and two monomeric enzymes with M(r) of 38,000 and 34,000 were
      purified from monkey kidney. The dimeric enzyme exhibited high dihydrodiol
      dehydrogenase activity and was immunochemically identical to dimeric dihydrodiol
      dehydrogenase of monkey kidney. The two monomeric enzymes exhibited aldehyde
      reductase activity, but were clearly distinct from each other in substrate
      specificity, inhibitor sensitivity, and effect of sulfate ions. One enzyme was
      immunologically cross-reacted with human liver aldehyde reductase, whereas
      sequence data of digested peptides from the other enzyme revealed > 97% identity
      with human placental aldose reductase. Comparison of kinetic constants among the
      monkey kidney enzymes and aldoketo reductases from several mammalian tissues
      indicated that dimeric dihydrodiol dehydrogenase and aldose reductase exhibited
      higher catalytic efficiency for 3DG than did aldehyde reductase, carbonyl
      reductase, and monomeric dihydrodiol dehydrogenase.

PMID- 8274015
TI  - sn-1,2-diacylglycerol cholinephosphotransferase from pig liver: mixed micellar
      assay and kinetic analysis of the partially pure enzyme.
AB  - sn-1,2-Diacylglycerol cholinephosphotransferase from pig liver microsomes was
      partially purified through a procedure involving solubilization with sodium
      cholate and chromatography on Sepharose 6B. The resulting preparation was 19-fold
      enriched with respect to microsomes and was shown to be very sensitive to
      different detergents. Sodium cholate gave the best yields in activity. In a mixed
      micellar assay with Triton X-100 a strong dependence of the enzyme activity on
      the concentration of mixed micelles was observed, due to Triton X-100 acting as
      an inactivator. Soja phosphatidylcholine added exogenously protected the enzyme
      against detergent inactivation and stimulated the enzyme activity. Dioleoyl
      phosphatidylcholine had a similar stimulatory effect, whereas didecanoyl- or
      dioctanoyl-phosphatidylcholine did not; thus long-chain phosphatidylcholines seem
      to be essential in the activation of cholinephosphotransferase. In a mixed
      micellar assay with sodium cholate no inactivation of the enzyme could be
      detected and it was found that soja phosphatidylcholine stimulates the activity
      in a greater extent than in Triton X-100 mixed micelles. The phospholipid
      activates the enzyme in a noncompetitive way with an activation constant of 176
      mol%. Km was estimated as 1.54 mol% with a Vmax = 30 nmol/min/mg protein. Those
      results support an activation mechanism by phosphatidylcholine interacting at
      sites different from the active center. The high activation constant led to the
      conclusion that cholinephosphotransferase requires a lipidic boundary for full
      activation. No activation by substrate was observed. Short-chain diacylglycerides
      such as dihexanoyl-, dioctanoyl-, or didecanoylglycerol can be used as substrates
      although the enzyme in this case has only 5 to 10% of the activity it has for
      dioleoylglycerol or egg diglycerides.

PMID- 8274016
TI  - Kallidin-releasing enzyme from Bitis arietans (puff adder) venom.
AB  - A kallidin-releasing enzyme with arginine ester hydrolytic activity was isolated
      from Bitis arietans venom by Sephadex G-75, DEAE-cellulose, and Sephadex G-100
      column chromatography. This enzyme was shown to be homogeneous as demonstrated by
      a single band on polyacrylamide gel electrophoresis, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and NH2-terminal sequence analysis. The
      molecular weight was determined to be 58,000 Da with an isoelectric point of 4.4.
      Kallidin-releasing enzyme possesses proteolytic activity demonstrated by the
      hydrolysis of Gly(8)-Ser(9), Ala(14)-Leu(15), Tyr(16)-Leu(17), and Phe(25)
      Tyr(26) bonds of oxidized insulin B chain. This enzyme did not convert fibrinogen
      to fibrin, yet it did hydrolyze the A alpha, B beta, and gamma chains of
      fibrinogen. The enzyme was shown to cleave a kininogen analog with the release of
      kallidin. Arginine ester hydrolytic activity of the preparation was inhibited by
      diisopropyl fluorophosphate and benzamidine hydrochloride, suggesting that serine
      and glutamic acid or aspartic acid are involved in this activity. This protein
      was stable to heat and over the pH range of 3-12.

PMID- 8274017
TI  - Structural study of the sugar chains of porcine factor VIII--tissue- and species
      specific glycosylation of factor VIII.
AB  - The asparagine-linked sugar chains of blood coagulation factor VIII purified from
      porcine plasma were released as oligosaccharides by hydrazinolysis. These sugar
      chains were converted to radioactive oligosaccharides by reduction with sodium
      borotritide and separated into neutral and acidic fractions by paper
      electrophoresis. Most of the acidic oligosaccharides were converted to neutral
      ones by sialidase digestion, indicating that they are sialyl derivatives. The
      neutral and the sialidase-treated acidic oligosaccharides were fractionated by
      serial chromatography on immobilized lectin columns. Structural study of each
      oligosaccharide by sequential exoglycosidase digestion and by methylation
      analysis revealed that porcine factor VIII contains high mannose-type and bi-,
      tri-, and tetraantennary complex-type sugar chains. Sixty-seven percent of the
      complex-type sugar chains contained the Gal alpha 1-->3Gal group, and 23% of the
      biantennary complex-type sugar chains contained the bisecting N-acetylglucosamine
      residue. These structures were not detected in the sugar chains of human plasma
      factor VIII. An in vitro competition study of von Willebrand factor and anti-Gal
      antibody for binding to factor VIII revealed that von Willebrand factor prevented
      antibody binding to Gal alpha 1-->3Gal groups in porcine factor VIII sugar
      chains. This suggests that anti-Gal antibody present in human plasma may not
      interact with the sugar chains of therapeutic porcine factor VIII. Reverse
      transcription polymerase chain reaction was used to identify porcine tissues
      producing FVIII mRNA. These studies revealed that the kidney is one of the major
      tissues expressing factor VIII which may contain the sugar chains with the
      bisecting N-acetylglucosamine residue.

PMID- 8274018
TI  - Ascorbic acid and collagen synthesis: rethinking a role for lipid peroxidation.
AB  - Ascorbic acid positively affects the synthesis of collagen, the most abundant
      extracellular protein. The mechanism by which ascorbate mediates the increased
      synthesis is debated. One recent hypothesis suggests that ascorbic acid induces
      an increase in lipid peroxidation and that this increase, in some manner, up
      regulates collagen gene expression. Evidence is presented that indicate increases
      in lipid peroxidation [thiobarbituric acid (TBA)-reactive material] is
      coincidental to collagen increases in ascorbate-treated cells, not a causal
      factor. Thus, cell impermeable iron chelators totally abolish ascorbate-mediated
      lipid peroxidation but do not affect collagen synthesis in the least. Decreases
      in TBA-reactive products seen at higher ascorbate levels (indicative of the well
      known pro- to antioxidant conversion of ascorbate in vitro) are paralleled by
      decreases in collagen synthesis. The decrease seen in collagen is completely
      reversed by treatment of the cell cultures with superoxide dismutase and catalase
      while the measure of lipid peroxidation is unaffected by coincubation with these
      antioxidant enzymes. Additionally, incubation conditions used to measure
      ascorbate induction of TBA-reactive material (buffers vs media, adherent vs
      detached cells) were found to be very important and results support the thesis
      that lipid peroxidation and collagen synthesis can be dissociated. While these
      results do not rule out a role for lipid mediators in regulating collagen
      synthesis at some level, they suggest this mechanism need not be involved for
      collagen increases seen in ascorbic acid-treated cells.

PMID- 8274019
TI  - Vanadate-mediated hydroxyl radical generation from superoxide radical in the
      presence of NADH: Haber-Weiss vs Fenton mechanism.
AB  - The mechanism of hydroxyl (.OH) radical generation from O2- and H2O2 by vanadate
      [V(V)] and the role of NADH in this reaction have been investigated using
      electron spin resonance (ESR) and spin trapping techniques. The results show that
      the reaction of V(V) with O2- (generated via xanthine/xanthine oxidase) does not
      generate any ESR detectable V(IV) ion or .OH radical and the addition of H2O2 has
      little effect on the radical yield. In the presence of NADH, however, the
      xanthine/xanthine oxidase/V(V) system generates .OH as well as V(IV), the
      formation of both of which could be suppressed by superoxide dismutase. Catalase
      inhibits the .OH formation but enhances V(IV) generation. Reaction of V(V) with
      NADH alone in the presence of phosphate buffer also causes .OH radical generation
      albeit at a much reduced rate, and superoxide dismutase reduces the .OH yield.
      These observations indicate, in contrast to earlier reports, that O2- does not
      reduce V(V) to V(IV) in the absence of NADH. It is concluded that vanadate
      generates the .OH radical via not a Haber-Weiss but a Fenton-like reaction [V(IV)
      + H2O2-->V(V) + .OH+OH-], the V(IV) and H2O2 being generated by V(V)-stimulated,
      O(2-)-dependent NADH oxidation.

PMID- 8274021
TI  - Site-specific mutagenesis of the metal binding sites of porcine fructose-1,6
      bisphosphatase.
AB  - Mutations in the metal binding sites of porcine fructose-1,6-bisphosphatase were
      carried out by site-specific mutagenesis based on the crystal structure of the
      enzyme. The mutant and wild-type enzymes have been characterized by circular
      dichroism spectrometry and initial-rate kinetics. One of the mutant forms of
      fructose-1,6-bisphosphatase (Glu280Gln) is associated with a single metal site,
      whereas two other mutants (Glu97Gln and Asp118Asn) ligate two metal ions. The
      mutant enzymes exhibit very large decreases in kcat relative to the wild-type
      enzyme; however, other kinetic parameters, such as Km values, are not greatly
      altered. Metal binding cooperativity and binding affinity is decreased in the
      mutants compared to wild-type fructose-1,6-bisphosphatase. Mutations in the metal
      binding sites greatly enhance the enzyme's affinity for AMP, a potent regulator
      of fructose-1,6-bisphosphatase activity. The results of these investigations are
      fully consistent with predictions made on the role of specific amino acid
      residues at the metal binding sites in porcine fructose-1,6-bisphosphatase from X
      ray diffraction studies [Zhang, Y., Liang, J.-Y., Huang, S., Ke, H., and
      Lipscomb, W.N. (1993) Biochemistry, 32, 1844-1857].

PMID- 8274020
TI  - Molecular cloning of a novel isotype of Mg(2+)-dependent protein phosphatase beta
      (type 2C beta) enriched in brain and heart.
AB  - Two complementary DNA (cDNA) clones (pTK-1 and -2) encoding two distinct isotypes
      of mouse Mg(2+)-dependent protein phosphatase beta (MPP beta-1 and -2,
      respectively) were isolated from a melanocyte cDNA library. Although mouse pTK-1
      is orthologous to the rat cDNA (JW5) reported previously [Wenk, J., Trompeter,
      H.I., Pettrich, K.G., Cohen, P.T.W., Campbell, D.G., and Mieskes, G. (1992) FEBS
      Lett. 297, 135-138], pTK-2 is a novel cDNA clone. It was strongly suggested that
      the pTK-1 and -2 cDNAs are splicing variants of a single pre-mRNA. The difference
      in the amino acid sequences between MPP beta-1 and -2 was observed only at the
      carboxy-terminal regions. Both the recombinant MPP beta-1 and -2 expressed in
      Escherichia coli cells were immunoreactive to an anti-MPP beta antibody and
      exhibited Mg(2+)-dependent and okadaic acid-insensitive protein phosphatase
      activities with similar substrate specificities. Although the mRNA of MPP beta-1
      was expressed ubiquitously in various mouse tissues, that of MPP beta-2 was
      expressed exclusively in brain and heart. These results suggest the difference in
      the physiological roles of these two enzyme isotypes.

PMID- 8274022
TI  - Inhibitors of the proton-sucrose symport.
AB  - Sucrose transporters are important components of the assimilate partitioning
      pathway in many plants. In the results reported here, we examined the effect of
      several inhibitors on proton-coupled sucrose transport into plasma membrane
      vesicles isolated from sugar beet leaf tissue. Three compounds that are
      reversible inhibitors of glucose transporters, phlorizin, cytochalasin B, and
      forskolin, also inhibited the proton-sucrose symport. Additionally, several
      reagents that covalently modify specific amino acid residues, including p
      chloromercuribenzenesulfonic acid (PCMBS), N-ethylmaleimide (NEM), diethyl
      pyrocarbonate (DEPC), and Hg2+, were also examined. NEM was not an effective
      inhibitor of the symport under both energized (pH 6.0) and unenergized (pH 7.7)
      conditions. In contrast, PCMBS, DEPC, and Hg2+ blocked sucrose transport
      activity. However, in control experiments it was discovered that Hg2+, but not
      PCMBS or DEPC, dissipated the proton electrochemical potential difference (delta
      mu H) that drives sucrose accumulation. It was further demonstrated that Hg2+
      dissipated an imposed delta mu+H in protein-free liposomes, thus obscuring its
      effect on the sucrose symport. In time- and concentration-dependent inactivation
      experiments, it was shown that DEPC binding was substrate protectable, thereby
      implicating binding at or near the active site of the carrier. In contrast, PCMBS
      activity was not linked to substrate binding. DEPC activity was partially
      reversed with hydroxylamine. This is consistent with specific modification of a
      histidine residue. Preloading purified vesicles with free histidine did not slow
      the DEPC-dependent inactivation kinetics. Since these membrane vesicles are
      predominantly right-side out, the last observation is consistent with a DEPC
      sensitive site which is accessible from the outside face of the vesicle. The
      results with DEPC suggest that a histidine residue is at or near the active site
      of the sucrose symport and that this amino acid plays a critical role in the
      reaction mechanism.

PMID- 8274023
TI  - Cloning two isoforms of rat cyclooxygenase: differential regulation of their
      expression.
AB  - Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells:
      COX-1 encoded by a 2.8-kb mRNA, and a mitogen-inducible COX-2 encoded by a 4-kb
      mRNA. We have cloned the COX-1 and COX-2 cDNAs from the cDNA library constructed
      from lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages. The deduced
      amino acid sequence showed that COX-1 contained 602 amino acids, whereas COX-2
      contained 604 amino acids. There is 95% conservation of the nucleotide sequence
      in the open reading frame of COX-1 between the rat and the mouse, while the
      homology of the 3' untranslated region is 68% except for a 150 bp segment
      adjacent to the stop codon which is nonhomologous with the mouse. Transfection of
      both COX cDNAs into Cos-7 cells resulted in increased COX activity. In rat
      vascular smooth muscle cells, interleukin-1 beta selectively increased the
      expression of COX-2, but not that of COX-1, as assessed by enzyme activity,
      immunoprecipitation of COX proteins, and mRNA analysis. Only the brain among
      tissues tested exhibits basal expression of COX-2 as the major form of the
      enzyme. However, COX-2 mRNA was expressed in vivo in the lung and kidney, but not
      in the heart, after systemic administration of LPS, suggesting that COX-2 but not
      COX-1 plays a major role in producing COX-derived products of arachidonic acid
      during endotoxic shock. Thus, the two COX isoforms were differentially expressed,
      and COX-2 was selectively induced in response to inflammatory stimuli in rats.

PMID- 8274024
TI  - Denitrosation of the anti-cancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea
      catalyzed by microsomal glutathione S-transferase and cytochrome P450
      monooxygenases.
AB  - The alkylating agent BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] can be
      inactivated through denitrosation reactions catalyzed by both cytosolic and
      microsomal enzymes. While previous studies have identified a class mu glutathione
      S-transferase [rat transferase 4-4 (Yb2)] as a major catalyst of the cytosolic
      denitrosation reaction, the enzymatic catalysts of BCNU denitrosation in
      microsomal membranes have not been identified. In the present study, both NADPH
      and glutathione (GSH) were found to support BCNU denitrosation catalyzed by
      isolated rat liver microsomes. Treatment of rats with the microsomal enzyme
      inducers phenobarbital and dexamethasone increased NADPH-dependent liver
      microsomal BCNU denitrosation up to fivefold without major effect on the GSH
      dependent denitrosation activity. Although the NADPH-dependent activity was fully
      inhibited by antibody to NADPH-P450 reductase, purified NADPH-P450 reductase
      catalyzed BCNU denitrosation at rates that could only account for approximately 2
      3% of the microsomal activity. Other experiments, including selective inhibition
      of NADPH-dependent microsomal BCNU denitrosation by chemical and antibody
      inhibitors of cytochrome P450, competitive inhibition of P450-catalyzed
      cyclophosphamide and ifosfamide activation by BCNU, and reconstitution of the
      denitrosation reaction by purified P450 enzyme 2B1 (major phenobarbital-inducible
      P450 form), established an important role for cytochrome P450 in BCNU
      denitrosation. By contrast, GSH-dependent microsomal BCNU denitrosation was
      unaffected by cytochrome P450 inhibitors, but was inhibited, with varying degrees
      of selectivity, by the microsomal glutathione S-transferase inhibitors ethacrynic
      acid, bromosulfophthalein, and indomethacin. These studies establish that BCNU
      inactivation can be catalyzed by two independent microsomal enzyme systems and
      suggest that therapeutically useful improvements in BCNU antitumor activity might
      be achieved through differential inhibition of these enzyme systems in tumor as
      compared to extratumoral sites.

PMID- 8274025
TI  - Regulation of proliferation in JEG-3 cells by a 500-kDa Ca2+ sensor and
      parathyroid hormone-related protein.
AB  - JEG-3 cells are derived from human trophoblasts and demonstrated to express a 500
      kDa Ca2+ sensing protein, which elicits biphasic elevations of cytoplasmic Ca2+
      concentrations ([Ca2+]i) and mediates Ca2+ regulation of parathyroid hormone
      related protein (PTHrP) release from placental cytotrophoblasts. Cytocentrifuged
      JEG-3 cells were immunostained by monoclonal and polyclonal antiserum toward
      PTHrP (1-34) and (38-64). Elevation of external Ca2+ from 0.5 to 3.0 mM induced
      only a sluggish rise in [Ca2+]i and no stimulation of cAMP production despite a
      more than twofold elevation of PTHrP(1-34) release. Monoclonal antibodies
      recognizing functionally discrepant epitopes of the Ca2+ sensor protein
      substantiated uncoupling of this sensor in the Ca(2+)-regulated PTHrP release.
      Exogenous activation of protein kinase C by a phorbol ester strongly augmented
      the secretion of PTHrP(1-34), whereby uncoupling of the Ca2+ sensor was partially
      reversed. This functional differentiation was associated with reduced
      [3H]thymidine incorporation in JEG-3 cells. Proliferation of these cells was
      inhibited by 71% upon rise of extracellular Ca2+ from 0.5 to 3.0 mM, and this
      inhibition was abolished by antibody-mediated interference with the Ca2+ sensor
      function. PTHrP(1-86) and PTH(1-34) at concentrations up to 10(-7) M decreased
      proliferation and stimulated the cAMP content of JEG-3 cells. The findings
      support concomitant Ca2+ sensor and PTH/PTHrP receptor expression in JEG-3 cells,
      and that Ca2+ inhibits proliferation by actions on the Ca2+ sensor as well as by
      stimulation of PTHrP release possibly mediating autocrine growth inhibition.

PMID- 8274026
TI  - Expression of a male-specific cytochrome P450 isozyme (CYP2C11) in fa/fa Zucker
      rats: effect of phenobarbital treatment.
AB  - The present study determined the effect of genetic obesity and phenobarbital (PB)
      treatment on the expression and regulation of the hepatic cytochrome P450 enzyme
      (CYP2C11) in Fa/? and fa/fa Zucker rats. Hepatic CYP2C11 levels as determined by
      Western immunoblotting and associated enzymatic activity (testosterone oxidation
      at the 2 alpha position) were significantly lower in untreated fa/fa Zucker rats
      compared with that observed in Fa/? Zucker rats. There was no significant
      difference in the constitutive CYP2C11 steady-state mRNA level hybridizable to
      the cDNA (P450 16 alpha) or specific oligonucleotide probe (Northern and slot
      blot analyses) between fa/fa and Fa/? Zucker rats. The depressed constitutive
      CYP2C11 protein levels in fa/fa rats may be attributed to their low plasma
      testosterone and growth hormone levels; however, lack of differences in CYP2C11
      steady-state mRNA suggest post-transcriptional regulatory mechanism(s). Treatment
      with PB further suppressed hepatic CYP2C11 protein levels and activities in both
      fa/fa and Fa/? Zucker rats in comparison with that seen in controls. The level of
      CYP2C11 steady-state mRNA was significantly higher after treatment with PB in
      Fa/? Zucker rats, while no change was observed in fa/fa animals. The mechanism by
      which PB treatment fails to increase CYP2C11 steady-state mRNA levels in the
      fa/fa Zucker rat is unknown; however, it may share a common molecular basis with
      the defect in nuclear transcription rate previously observed with CYP2B1/2B2.

PMID- 8274027
TI  - Uronic acid-containing glycosaminoglycans and keratan sulfate are present in the
      tectorial membrane of the inner ear: functional implications.
AB  - The tectorial membrane is a gel-like, acellular connective tissue overlying the
      microscopic organ of Corti--the auditory sensory structure. It is instrumental in
      the sound-synchronous deflection of the stereocilia of the hair cells, a central
      event in auditory transduction. It is well established that collagen, primarily
      type II, constitutes the major protein of the tectorial membrane, with smaller
      amounts of types IX and XI also present. However, conclusive information on the
      proteoglycans in this structure is lacking. Tectorial membranes were extracted
      with a 4 M guanidine--HCl solvent, and proteoglycans isolated after ethanol
      precipitation and collagenase treatment. A colorimetric assay based on the
      binding of the cationic dye safranin O to glycosaminoglycans, in combination with
      enzymatic techniques, detected significant amounts of chondroitin sulfate and
      keratan sulfate (0.29 and 0.17% on a wet weight basis, respectively). Agarose
      polyacrylamide electrophoresis of chondroitinase-digested samples revealed a core
      protein with a similar molecular mass to that of the large cartilage proteoglycan
      aggrecan. This proteoglycan reacted with the antibody 3-B-3 (recognizing modified
      chondroitin 6-sulfate linkage region oligosaccharides). Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis revealed several low molecular mass proteins
      which reacted with 5-D-4, specific for keratan sulfate, one of which showed
      characteristics of fibromodulin. Comparison of the quantitative aspects of
      various connective tissue components of tectorial membrane with other type II
      collagen-containing structures revealed that this tissue resembles highly
      hydrated cartilage.

PMID- 8274028
TI  - Irreversible inactivation of monoterpene cyclases by a mechanism-based inhibitor.
AB  - Monoterpene synthases (cyclases) catalyze the divalent metal ion-dependent
      transformation of geranyl pyrophosphate to representative of the various
      monocyclic and bicyclic skeletal types by an electrophilic reaction mechanism
      involving coupled isomerization and cyclization steps. An analogue of the geranyl
      substrate, in which the terminal gem-dimethyl groups were joined to form a
      cyclopropyl function (6-cyclopropylidene-3E-methyl-hex-2-en-l-yl pyrophosphate)
      was shown to be a potent inhibitor of (-)-4S-limonene synthase from Mentha
      spicata and of several other monoterpene cyclases from diverse plant species.
      Inhibition was concentration and time dependent (pseudo-first-order kinetics), as
      well as absolutely contingent on the presence of the divalent metal ion cofactor.
      A double reciprocal plot of kinactivation versus inhibitor concentration gave an
      apparent Ki of approximately 0.3 microM and a maximum rate of inactivation of
      about 0.3 min-1 with limonene synthase. As expected for an active-site-directed
      process, the natural substrate, geranyl pyrophosphate, afforded protection
      against inactivation by the cyclopropylidene analogue. Selectivity of the
      inhibition was demonstrated with [1-3H]6-cyclopropylidene-3E-methyl-hex-2-en-1-yl
      pyrophosphate by specific labeling of limonene synthase in crude enzyme extracts
      as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, radio
      fluorography, and immunoblotting. The radioactive cyclase-inactivator complex was
      formed with 1:1 stoichiometry and was stable to extended dialysis and boiling in
      2% sodium dodecyl sulfate, suggesting irreversible covalent modification of the
      enzyme involving a chemical reaction between cyclase and inhibitor. Thermally
      denatured limonene synthase and synthase that had been inactivated with the
      histidine-directed reagent diethylpyrocarbonate or the cysteine-directed reagent
      p-hydroxymercuribenzoate (two reagents known to modify the active site of the
      enzyme and inhibit catalysis) were not labeled when treated with the [1-3H]
      analogue, indicating that the functional enzyme was necessary to effect complex
      formation. All of the evidence is consistent with the analogue serving as a
      mechanism-based inactivator that must undergo both ionization-dependent
      isomerization and cyclization steps to reveal an allylic cation which alkylates
      the protein. In addition to furnishing supporting evidence for the electrophilic
      reaction sequence, this mechanism-based inactivator provides a powerful new
      approach for the examination of cyclase active sites.

PMID- 8274029
TI  - Identification, cloning, and expression of the gene for adenylate kinase from the
      thermoacidophilic archaebacterium Sulfolobus acidocaldarius.
AB  - An adenylate kinase gene from a member of the archaebacterial kingdom, the
      thermoacidophilic archaebacterium (archaeon) Sulfolobus acidocaldarius, has been
      cloned and sequenced for the first time. Two degenerate oligonucleotide probes,
      based on the N-terminal amino acid sequence information, led to the amplification
      of a gene-specific DNA fragment, used to screen subgenomic libraries. Comparing
      the DNA-derived amino acid sequence of total 194 residues with those of known
      procaryotic and eucaryotic adenylate kinases revealed only a low degree of
      similarity, except for a glycine-rich region close to the N-terminus, the so
      called P-loop. Using inducible expression systems catalytically active S.
      acidocaldarius adenylate kinase was produced in large amounts. Although the total
      length of the protein and the results of alignment procedures suggest a closer
      relation to eucaryotic than to procaryotic sequences, the archaebacterial enzyme
      may represent a novel class of adenylate kinases. This is corroborated by the
      finding that an antiserum against this protein does not cross-react with
      Escherichia coli nor yeast or rabbit adenylate kinases for example.

PMID- 8274030
TI  - Structural and biologic properties of a human aspartic acid-126 interleukin-2
      analog.
AB  - Point mutations at position 141 in the murine interleukin-2 (IL-2) sequence have
      been reported to generate proteins with full antagonist activity on some IL-2
      dependent cell lines. To evaluate the potential therapeutic utility of this
      observation, we have prepared recombinant human IL-2 with a point mutation at the
      corresponding position (Asp for Gln 126) and examined its structural and biologic
      properties. This mutation apparently induces minor changes in tertiary
      conformation accompanied by an increased sensitivity to changes in pH. The
      biologic activity of this analog is greatly reduced, primarily as a result of
      decreased affinity to the beta/gamma IL-2 receptor complex; however, it is only
      weakly antagonistic to the IL-2 response of normal peripheral blood lymphocytes.

PMID- 8274031
TI  - Resolution and identification of C4 phosphoenolpyruvate-carboxylase protein
      kinase polypeptides and their reversible light activation in maize leaves.

PMID- 8274032
TI  - Monohydroxy fatty acids esterified to phospholipids are decreased in lesional
      psoriatic skin.
AB  - Because of the increasing number of reports of the important roles of monohydroxy
      derivatives of poly-unsaturated fatty acids in the regulation of cell function,
      we determined the pools of unesterified and esterified monohydroxy fatty acids
      (MHFAs) in keratomed epidermal slices, taken from lesional and non-lesional
      psoriatic skin. Extracted phospholipids were separated by thin-layer
      chromatography. The isolated fractions of phosphatidylcholine (PC),
      phosphatidylinositol (PI) and phosphatidyl-ethanolamine (PE) were treated with
      phospholipase A2 to release fatty acids in the sn-2 position. Released MHFAs were
      separated by reversed-phase and straight-phase high-performance liquid
      chromatography and identified as the linoleic acid derivatives 9-hydroxy
      octadecadienoic acid (9-HODE) and 13-hydroxy-octadecadienoic acid (13-HODE) and
      as the arachidonic acid derivative 15-hydroxy-eicosatetraenoic acid (15-HETE).
      These findings are consistent with the presence of unesterified 9-HODE, 13-HODE
      and 15-HETE. In contrast, 12-hydroxy-eicosatetraenoic acid (12-HETE), although
      found to be present in high amounts as unesterified 12-HETE, was not detectable
      in the phospholipids. When compared with non-lesional psoriatic skin, the levels
      of 9-HODE, 13-HODE and 15-HETE esterified to the sn-2 position of PC, PI and PE
      in lesional psoriatic skin were significantly decreased (to 28-78% of those in
      non-lesional skin). This depletion of MHFAs in specific phospholipids may be due
      to an imbalance between phospholipase and acyltransferase activities. Because the
      levels of esterified MHFAs may influence signal transduction and eicosanoid
      metabolism the described changes may be relevant for the inflammatory processes
      occurring in psoriasis.

PMID- 8274033
TI  - Co-culture of human melanocytes and keratinocytes in a skin equivalent model:
      effect of ultraviolet radiation.
AB  - Melanocytes grown in pure monolayer culture lack the three-dimensional
      organization and many of the cellular interactions that exist in vivo. This can
      be partially overcome by growing melanocytes together with other epidermal cells
      in skin equivalent models. In this study skin equivalents were prepared by
      seeding mixtures of cultured human keratinocytes and melanocytes in various
      ratios onto de-epidermized dermis. They were cultured in DMEM/Ham's F12 (3:1) for
      3 days and then lifted to the air-liquid interface and maintained for 11 days.
      Histological examination revealed a structure that closely resembled human
      interfollicular epidermis. Melanocytes, identified by their dendritic appearance,
      positive dopa reaction and positive staining with a melanocyte-specific antibody
      (MEL5), were located in the basal layer. Melanin was seen both in melanocytes and
      in neighbouring keratinocytes. Whilst the skin equivalent became more pigmented
      following UV irradiation (total UVB 4760 J/m2 over 3 days), the quantity and
      distribution of melanin at the light microscopic level appeared to be unchanged.
      However, the number and dendricity of melanocytes increased, as did their
      staining with dopa and MEL5. These results indicate that melanocytes are
      functional and capable of responding to UV irradiation.

PMID- 8274034
TI  - Characterization and analysis of human papillomaviruses of skin warts.
AB  - We analysed human papillomavirus (HPV) infections in 61 tissue specimens of skin
      warts of Taiwanese patients by DNA hybridization. The prevalence of HPV infection
      was 69% by Southern blot hybridization. The typing of HPVs was performed by dot
      blot hybridization under highly stringent conditions with each probe separately.
      The prevalence of HPV-1, 2/3, 4, 5, 8, 11, 16 and 18 in skin warts was 13, 7, 16,
      2, 0, 5, 2 and 8%, respectively. Chi-squared analysis revealed that there was a
      correlation between HPV type and copy number. Most HPV-4-induced warts were
      verruca vulgaris. HPV-1 DNA was detected in verruca plantaris and verruca
      vulgaris. No specific histopathological features were found to be indicative of
      the presence or absence of HPV, or of the various types of HPV infection.

PMID- 8274035
TI  - Development of a stratum corneum and barrier function in an organotypic skin
      culture.
AB  - The stratum corneum of human skin is responsible for maintaining the epidermal
      permeability barrier. We have developed a bilayered skin culture (SC) which forms
      a corneum 35 +/- 1 cell layers thick 21 days after being raised to the air-liquid
      (A/L) interface. By the 7th day after raising to the A/L interface the
      corneocytes were irregularly shaped and had cross-sectional areas (CSA) of > or =
      300 microns 2. By the 21st day the corneocytes had assumed polygonal shapes and
      had a CSA (100-250 microns 2) similar to that of human foreskin. The total lipid
      (TL) content of the corneum averaged 5-7% of the lyophilized weight. Ceramide
      content increased from 20% of TL at day 7 of A/L interface culture to 30% at day
      21. Triglycerides decreased from 43% to 17% of TL during the same period. Free
      fatty acids comprised 5.5% of TL at day 21 of A/L interface culture. The
      intercorneocyte spaces contained stacks of lipid lamellae. However, the stacks
      lacked the Landmann unit repeat. Abnormal lamellar structures were observed in
      both the intra- and extracorneocyte spaces. Transepidermal water loss (TEWL) was
      > 4 mg/cm2 per h throughout the culture period. Lipid supplementation of the
      culture medium and culturing in a low humidity environment improved barrier
      function by 50%. However, the effects were not additive. The SC developed a near
      normal corneum, but did not achieve barrier competence, due at least partially to
      abnormalities in lipid composition and organization.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8274036
TI  - Morphometry of human epidermis in vivo by real-time confocal microscopy.
AB  - Real-time confocal microscopy has brought substantial improvements to the imaging
      of the human skin in vivo. On early images, the stratum corneum could be
      distinguished from the living epidermis and the circulatory network of the
      superficial dermis. We have adapted the Tandem Scanning Microscope to obtain
      images of the living skin, showing thinner structures such as the stratum lucidum
      and the dermo-epidermal junction, both of which are essential markers for micron
      order measurements of the thickness of the stratum corneum and living epidermis.
      The measurements were corrected for the differences in the refractive index of
      the various cutaneous layers, and the undulation of the dermo-epidermal junction.
      Furthermore, nucleus size and number could be assessed from horizontal optical
      sections. To illustrate the sensitivity of the thickness measurements, changes in
      the thickness of the epidermis were recorded during and after stripping of the
      horny layers. This non-invasive methodology is a very promising tool for
      morphometric studies of the living human skin at the cellular level.

PMID- 8274037
TI  - Loricrin immunoreactivity in human skin: localization to specific granules (L
      granules) in acrosyringia.
AB  - Loricrin is a major component of the cornified cell envelope and is also
      expressed in the granular layer of human epidermis. In newborn mouse epidermis,
      loricrin accumulates in small round granules (L-granules) in the granular layer
      before being incorporated into the cornified cell envelope, but the expression of
      L-granules has not yet been demonstrated in human skin. In the present study we
      used postembedding immunoelectron microscopy to examine loricrin expression in
      normal human skin. We observed diffuse loricrin staining in the uppermost
      granular cell layer in interappendageal epidermis, that was not associated with
      any granular structures. In the cornified cells, most of the labelling was on the
      inner face of cornified cell envelopes. By contrast, in the upper segment of
      acrosyringia there were small granules (L-granules) that specifically labelled
      for loricrin. In the outer ductal cells, L-granules with a highly osmiophilic
      electron density were apparent in the nucleus as well as in the cytoplasm. In the
      inner ductal cells, L-granules were round or oval, less electron-dense and larger
      than the outer ductal L-granules, and present only in the cytoplasm. Some of the
      outer ductal L-granules and most of the inner ductal L-granules formed composite
      granules with filaggrin immunoreactive granules. These results suggest that in
      human interappendageal epidermis, loricrin might be rapidly incorporated into the
      cornified cell envelope without prior accumulation in any type of granule. By
      contrast, in acrosyringia loricrin accumulates in granules, perhaps reflecting
      increased synthesis or slower processing. The significance of the different
      morphological features of the L-granules in inner and outer acrosyringial cells
      remains to be clarified.

PMID- 8274038
TI  - Fractionation of Paget cells in extramammary Paget's disease.

PMID- 8274039
TI  - Gene expression of tumour necrosis factor-alpha (TNF-alpha) and heat-shock
      protein (HSP) 70 in patients with Behcet's disease.

PMID- 8274040
TI  - Heparin as a chemoattractant for mouse spermatozoa.

PMID- 8274041
TI  - Sperm morphology in fertile men.
AB  - Sperm morphology was assessed in 78 fertile men according to the Dusseldorf
      classification. There were 30% normal forms on average, which conforms with the
      new World Health Organization guidelines. This differs from the strict criteria
      of the Tygerberg group [9] probably due to the fact that these criteria were
      established under in vitro conditions.

PMID- 8274042
TI  - Specificity of ATP for the initiation of flagellar motility of hamster sperm.
AB  - Hamster sperm collected from the cauda epididymis were washed and the pellet
      diluted in a medium containing Triton x 100 (Sigma, Saint Louis, MO, USA) to
      dissolve the cell membrane and then reactivated with various concentrations of
      ATP (0-3 mM). Spermatozoal axonemes were initially immotile but the maximal
      percentage motility was obtained almost immediately following addition of 1 mM
      ATP. A stepwise increase in the concentration of ATP caused a 5-min delay in
      development of maximal reactivation and a change in the beating pattern as
      indicated by a decrease in the percentage of reactivating sperm. Under the same
      experimental condition GPT, UTP, CTP, and AMP failed to initiate the axonemal
      motility. In demembranated sperm reactivated by ADP, however, the beat frequency
      was lower compared with that reactivated by ATP. Pretreatment of the sperm with
      the mitochondrial phosphorylation blockers oligomycin and 2'4'-DNP
      (dinitrophenol) failed to inhibit the axonemal movement, although the presence of
      the dynein ATPase inhibitor, vanadate, was able to inhibit the reactivation.
      These results suggest that the exogenous ATP, but not the mitochondrial ATP, is
      responsible for axonemal motility.

PMID- 8274043
TI  - Effect of IR laser radiation on germ cell DNA content after one cycle of the
      seminiferous epithelium.
AB  - The effect of IR laser radiation on rat germ cells was investigated by
      cytophotometric quantification of the nuclear DNA content after a 15-day resting
      period. Two different doses of radiation energy were applied: 28.05 J/cm2 and
      46.80 J/cm2. Both doses were found to increase the percentages of both
      spermatogonia with a 4c DNA content and primary spermatocytes with a > 4c DNA
      content. The elongating and elongated spermatids had a c DNA nuclear content,
      except for a small proportion (5%) of elongating cells that displayed a 2c DNA
      content at 28.05 J/cm2. Results revealed an increase in the germ cell DNA content
      after one cycle of the seminiferous epithelium after in vivo exposure to IR laser
      light. The laser sensitivity of the germ cells appeared to be related to their
      stage of differentiation and to the radiation energy applied, and the
      spermatogonia were the most sensitive. In all cases the lowest dosage induced the
      highest alteration.

PMID- 8274044
TI  - Human sperm function after coculture with human fallopian tubal epithelial cell
      monolayers: in vitro model for studying cell interactions in early human
      conception.
AB  - It has been difficult to study the behavior of sperm in the tubal environment in
      vivo. Human tubal epithelial cells were therefore cultured in vitro to simulate
      tubal conditions and human sperm function was assessed in the presence of such
      cells in vitro. Ampullary epithelial cell lines were established from fallopian
      tubes collected from premenopausal women undergoing hysterectomy. Approximately 1
      x 10(5) cells/mL from monolayers of the third passage were seeded with 1 mL of
      culture medium into each well of 4-well plastic dishes. Sperm from 10 ejaculates
      of 10 different oligoasthenozoospermic men 30-41 years of age were recovered by
      the swim-up method and 200,000 sperm from each ejaculate were added into each
      well at the time of cell seeding. Control wells were treated the same but without
      cells. All dishes were incubated at 37 degrees C in 5% CO2, and sperm motility,
      acrosome reaction, and sperm-cell binding assessed at 1, 5, and 24 h. Curvilinear
      velocity and mean amplitude of lateral head displacement were significantly
      different in ampullary cultures as compared with controls for all three time
      periods: 1 h (67 +/- 5.2 vs 58 +/- 4.9 microns/s, p < 0.05; 4.48 +/- 0.4 vs 3.29
      +/- 0.3 microns; p < 0.05), 5 h (75 +/- 5.8 vs 64 +/- 5.0 microns/s, p < 0.05;
      4.92 +/- 0.5 vs 3.68 +/- 0.3 microns, p < 0.05), and 24 h (70 +/- 4.8 vs 59 +/-
      4.2 microns/s, p < 0.05; 4.36 +/- 0.4 vs 3.11 +/- 0.3 microns, p <
      0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274045
TI  - Role of the spermatic artery in spermatogenesis and sex hormone synthesis.
AB  - This study was conducted to determine whether the spermatogenesis of testes and
      the serum sex hormone synthesis are influenced by the ligation of spermatic
      arteries. Sixteen adult male dogs were randomly divided into four groups. From
      our preliminary data the spermatogenic arrest and decrease of testicular volume
      were noted prominently in dogs after ligation of spermatic arteries. The serum
      testosterone level decreased and the serum luteinizing hormone level increased
      significantly in the same groups, while no significant changes were found in the
      dogs with preserved spermatic arteries. There were no significant differences in
      the epididymis and serum follicle-stimulating hormone among the four groups. This
      study attempted to establish the critical role of spermatic arteries in
      testicular function.

PMID- 8274046
TI  - Effect of heparin on capacitation/acrosome reaction of equine sperm.
AB  - The onset of sperm capacitation/acrosome reaction was evaluated using heparin.
      Equine semen was incubated at 38 degrees C for 4.5 h in culture medium with and
      without 10 micrograms/mL heparin and with and without 0.1 microM of Ca2+
      ionophore. Sperm acrosome reaction was detected using chlortetracycline
      fluorescence (CTC) and transmission electron microscopy (TEM). The CTC assay
      provided staining patterns that corresponded with the capacitation/acrosome
      reaction in other mammalian species (man, mouse, guinea pig). The percentages of
      incapacitated sperm (PUC), capacitated acrosome-intact sperm (PC), and acrosome
      reacted sperm (PAR) were evaluated following incubation times of 0.5 and 4.5 h in
      heparin-free and heparinized medium, and at 4.5 h only in sperm exposed to Ca2+
      ionophore. The CTC assay was highly correlated with TEM for estimation of PAR. At
      4.5 h, heparinized medium reduced PUC and increased PC and PAR, in comparison
      with heparin-free medium. Addition of Ca2+ ionophore to the medium reduced PUC
      and increased PC and PAR at 4.5 h, as compared with sperm in ionophore-free
      medium. Incubation time also affected PUC, PC, and PAR in heparin-free and
      heparinized medium without ionophore. The PUC was greater at 0.5 h than at 4.5 h,
      and PC and PAR were less at 0.5 h than at 4.5 h. It would appear that the
      initiation of capacitation/acrosome reaction of equine sperm in vitro is
      accelerated by heparin.

PMID- 8274047
TI  - Epididymal markers in an andrology clinic.
AB  - The ability of the markers alpha-glucosidase, carnitine, and
      glycerylphosphorylcholine to indicate epididymal obstruction was studied. alpha
      Glucosidase was found to be the best discriminant, with 93.4% correct
      classifications. The possible interrelationship between alpha-glucosidase
      activity, sperm ATP, and epididymal function was then studied. alpha-Glucosidase
      correlated positively with the percentage of motile sperm (p = 0.0212) and with
      the percentage of sperm with good forward progression (p = 0.0374), but
      correlated negatively with the sperm ATP (p < 0.0500). It was concluded that
      lower ATP and higher alpha-Glucosidase may be markers of efficient epididymal
      function. The possible epididymal origin of detached ciliary tufts (DCTs) was
      studied by determining ATP and alpha-glucosidase activity in patients with DCTs.
      The mean ATP in patients with DCTs was significantly higher (p = 0.009), but the
      alpha-glucosidase activity significantly lower (p = 0.0412) than in the control
      group. These results seem to support the epididymal origin of DCTs.

PMID- 8274048
TI  - Concentrations of vasoactive intestinal polypeptide in corpus cavernosum and
      peripheral venous blood during prostaglandin E1-induced erection.
AB  - Vasoactive intestinal polypeptide (VIP) has been suggested to play a role as a
      nonadrenergic, noncholinergic neurotransmitter or neuromodulator involved in the
      process of erection. Until now, data about fluctuating concentrations of VIP in
      corpus cavernosum (CC) blood have been controversial. The present study describes
      a modified radioimmunoassay method that was developed in our laboratory for the
      determination of VIP in plasma. Examination of 12 patients suffering from
      impotentia coeundi (6 men with psychogenic impotence, 2 with induratio penis
      plastica, and 4 with impotence of vascular origin) showed that the concentrations
      of VIP in corpus cavernosum blood during pharmacologically induced erection did
      not increase in organically healthy men or in men with impotentia coeundi of
      vascular origin. The VIP concentrations in peripheral venous blood and those in
      CC blood were similar.

PMID- 8274049
TI  - Comparative evaluation of three sperm-washing methods to improve sperm
      concentration and motility in frozen-thawed oligozoospermic and normozoospermic
      samples.
AB  - Three sperm-washing methods (direct layering without centrifugation, DL; ficoll
      entrapment, F; and percoll gradient, P) were evaluated for sperm recovery and
      motility using computer-automated semen analysis on frozen-thawed samples from
      normozoospermic and oligozoospermic men. The motile sperm recovery after freeze
      thawing was significantly greater for normozoospermic compared with
      oligozoospermic samples (43 +/- 5.08% vs 15.76 +/- 3.53%; p < 0.001). The P
      separated prelayer gave significantly higher recovery of motile sperm than the DL
      and F methods for both oligozoospermic (0.51 +/- 0.14 vs 0.19 +/- 0.05; p < 0.05)
      and normozoospermic samples (9.74 +/- 3.11 to 43 +/- 6.01 vs 0.88 +/- 0.23 to
      15.30 +/- 3.12; p < 0.001). The P-separated postlayer had higher curvilinear
      velocities than the DL, F, and prelayered P methods for oligozoospermic samples
      only (71 +/- 5.13 microns/s vs 53 +/- 3.67 to 59 +/- 2.72 microns/s; p < 0.05).
      Mean amplitude of lateral head displacement values were significantly different
      for postlayered P-treated sperm compared with DL, F, and prelayered P-treated
      sperm for normozoospermic samples only (4.25 +/- 0.16 to 4.67 +/- 0.32 vs 3.01 +/
      0.14 to 3.67 +/- 0.19; p < 0.05). Percoll separation without layering may be the
      best washing method for both normozoospermic and oligozoospermic frozen-thawed
      sperm, and the treatment of such recovered sperm with a motility-enhancing agent
      such as pentoxyfylline may yield optimum fertilization rates.

PMID- 8274050
TI  - [Gene therapy in the CNS].

PMID- 8274051
TI  - Studies on early enteral nutrition for patients with gastric cancer from the view
      of immunity.
AB  - The enteral nutrition after operation for gastric cancer patients with special
      reference to its immunological improving effect was examined. The subjects were
      25 patients who underwent an operation and they were classified into 2 groups by
      the postoperative nutritional control method. E group: patients who received
      enteral nutrition after operation (n = 12) and T group those who reviewed TPN
      postoperatively (n = 13). In the 25 subjects the serum proteins, nitrogen balance
      and 3-methylhistidine (3-Mehis) were measured before and after the operation. The
      total lymphocyte counts were measured before and after operation. The total
      lymphocyte subsets and NK cell activity were determined with monoclonal
      antibodies. Nutritionally, there was no significant difference in the serum
      proteins and nitrogen balance and 3-Mehis/Cr ratio also showed no significant
      difference. Immunologically, an improving effect was observed in E group
      postoperatively with CD4+CD45R-Leu8- (helper T) cell subpopulation, CD8+CD11b-
      (cytotoxic T) cell subpopulation and CD3-CD16+CD56+ (NK-LAK) cell subpopulation.

PMID- 8274052
TI  - Study of effect of surgical stress on immunity in patients with gastrointestinal
      cancer.
AB  - We investigated the effect of surgical stress on immunity in patients with
      gastrointestinal cancer by three color flow cytometry centering on lymphocyte
      subsets. The control group consisted of patients with cholelithiasis as a benign
      disease and the cancer groups consisted of patients with gastric cancer and those
      with colorectal cancer. Total lymphocyte in peripheral blood, lymphocyte subsets
      by monoclonal antibody and NK cell activity were measured before and after
      operation in the target patients. The cell ratio of CD4+CD45R+Leu8+ (suppressor
      inducer T), CD8+CD11b+ (suppressor T) were significantly higher in the
      gastrointestinal cancer group when lymphocyte subsets were investigated after
      operation. Further, the cell ratio of CD3+CD16-CD56+ (T-LAK) was significantly
      lower. These findings suggest that decrease in immunity as a result of surgical
      stress is greater in patients with gastrointestinal cancer than in those with a
      benign disease.

PMID- 8274053
TI  - Relation of epidermal growth factor receptor concentration to growth of human
      esophageal cancer cell lines.
AB  - The relation between the concentration of epidermal growth factor (EGF) receptor
      and the effects of EGF on cell proliferation were studied using 16 newly
      established human esophageal cancer cell lines. According to 125I-EGF binding
      assay, the amount of EGF receptor was found to vary from 6 x 10(4) to 1.2 x 10(7)
      (sites/cell). Changes in EGF-stimulated tyrosine-specific protein kinase activity
      almost paralleled changes in the number of EGF receptors per cell. Amplification
      of EGF receptor gene was detected in only one cell line. Under monolayer culture
      conditions, we found three types of growth responses of esophageal cell lines to
      EGF; growth in 5 cell lines was inhibited and that in 4 cell lines was stimulated
      while that in the other 7 cell lines remained unaffected. Relation was observed
      between the number of EGF receptors per cell and the growth response to EGF. On
      the other hand, cell lines whose growth was inhibited by EGF in monolayer culture
      were stimulated by EGF in soft agar culture, though the opposite was not
      necessarily true.

PMID- 8274054
TI  - Leiomyosarcoma of the colon in a newborn: a case report and review of the
      literature.

PMID- 8274055
TI  - [Symptoms and natural history of cardiovascular diseases: obsolete?].
AB  - The role of symptoms in establishing a diagnosis in cardiovascular diseases has
      decreased. Treatment privileges action and underestimates the potentially
      favourable spontaneous outcome of the treated condition. The object of this
      article is not to question the progress made in presymptomatic diagnosis of
      certain cardiovascular diseases or the benefits of treatment prescribed for some
      a- or paucisymptomatic patients: recent reports, particularly in asymptomatic
      aortic regurgitation, silent ischemia and subclinical left ventricular
      dysfunction of cardiomyopathy have confirmed the utility of therapy in these
      cases. However, the risks of misinterpreting a symptom and the natural history
      should be underlined: the "complaint" of the patient not properly assessed;
      cascades of "complementary investigations" of debatable utility and uncertain
      interpretation, when taken out of context; substitution of the medical
      therapeutic offer on demand of the patient and inadequate patient education
      concerning possible therapeutic approaches: the quest for intermediary objectives
      (anatomic, physiologic, biologic), which have not been shown to increase the
      quality or duration of life; the disproportion between the small number of
      validated therapies and the ever increasing range of interventional audacities in
      asymptomatic patients... It is important that general pathology and the natural
      history of cardiovascular diseases are taught again in France. With respect to
      symptoms, proper assessment no longer depends on "clinical judgment"; it should
      have a greater role in diagnosis of cardiovascular diseases by the understanding
      of the physiopathological mechanisms, Bayesian assessment of its predictive
      value, and accurate inclusion in multiparameter scores derived from recent large
      scale epidemiologic and therapeutic trials.

PMID- 8274056
TI  - [Failure and complications of transesophageal echocardiography. Apropos of 1500
      consecutive cases].
AB  - Transesophageal echocardiography (TEE) requires the introduction of a flexible
      probe into the oesophagus and therefore cannot be strictly considered to be non
      invasive. This manipulation exposes the patient to complications which are benign
      in the large majority of cases. The authors report their experience in a
      prospective study analysing the failures and complications of TEE in the first
      1,500 cases performed in their laboratory between May 1988 and May 1992, in
      mainly adult and ambulatory patients. The probe could not be introduced in 24
      patients (1.6%), including 5 cases during the initial learning period. No serious
      complications were observed during of after TEE. Minor incidents were noted in 28
      cases (1.9%) intolerance of the probe (12 cases), nausea and/or vomiting (4
      cases), dyspnea (4 cases) due to tracheal intubation in 2 patients, laryngeal in
      1 patient and to cardiac failure in 1 case. Pharyngeal haemorrhage (2 cases),
      atrial fibrillation (3 cases), vertigo (1 case), mandibular dislocation (1 case)
      and salivary hypersecretion affecting the quality of the imaging (1 case), were
      also observed. The investigation had to be interrupted prematurely in 12 cases
      (0.8%) usually because of intolerance of the probe. These results show that TEE
      is not dangerous in trained hands. Failure to introduce the probe is usually
      encountered during the learning period, which reinforces the need for
      apprenticeship in a teaching center. The safety of this technique, plus its
      considerable diagnostic value in many clinical indications, justify its present
      role in everyday cardiological practice.

PMID- 8274057
TI  - [Early clinical, electrocardiographic and biological criteria of reperfusion
      after intravenous fibrinolysis during the acute phase of myocardial infarction].
AB  - Between May 1991 and February 1992, 31 consecutive patients were included in a
      prospective study, the aims of which were to determine the criteria of early
      coronary revascularisation after intravenous thrombolysis in the acute phase of
      myocardial infarction. The rise in serum myoglobin, the ST segment elevation,
      accelerated idioventricular rhythm and the evolution of chest pain were analysed.
      All patients underwent coronary angiography. Twenty-six were revascularized and 5
      remained with coronary occlusion. Two types of serum myoglobin curves were
      demonstrated. Those with a sudden , decrease and a well defined peak in the first
      4 hours were specific for revascularisation and easily identified (Group A: 16
      patients). The graphs with a progressively rising slope to a peak after the 4th
      hour were observed in patients with coronary occlusion, but also in 10 patients
      with recanalized arteries (Group B). No significant difference was demonstrated
      with regards to the clinical and coronary angiographic parameters between
      patients in Group A and Group B. On the other hand, the time between the onset of
      chest pain and peak myoglobin was shorter in Group A (298 +/- 81 min) than in
      recanalised patients in Group B (380 +/- 54 min) (p < 0.05). The difference in
      the profile of the serum myoglobin could therefore reflect restoration of
      arterial flow in myocardial cells which had not suffered the same period of
      ischemia. ST segment elevation may increase, decrease of remain stable at 120
      minutes in patients revascularised and those remaining occluded. In 9 patients,
      the ST elevation increased compared with the initial electrocardiogram .(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8274058
TI  - [8 years outcome of 243 trials of coronary angiography performed in the Montreal
      Institute of Cardiology].
AB  - This study reports the long-term outcome of the first 243 patients who underwent
      coronary angioplasty at the Montreal Heart Institute between February 1980 and
      March 1983. The average age of the patients was 50 +/- 9 years; one quarter of
      cases were unstable angina; three quarters of the patients were men. Single
      vessel coronary disease was present in 83% of patients; the mean ejection
      fraction was 62%. One segment was dilated in 216 patients and 2 segments in 27
      patients. The LAD was dilated in 179 patients, the right coronary in 63 and the
      left circumflex artery in 20 patients. The average severity of stenosis was 83 +/
      9.5%. Angioplasty was successful in 68.7% of patients. There were no fatalities:
      25.5% of patients underwent coronary bypass surgery; 6.2% of patients suffered
      myocardial infarction. Restenosis was observed in 28% of patients. The average
      follow-up period was 99 +/- 10 months (average 8 years) and ranged from 7 to 10
      years. The survival rate was 98.4% and 90.5% at 5 and 10 years respectively.
      Survival rates without infarction were 91.8% and 81.3% at 5 and 10 years, and
      survival without infarction or revascularisation was 73.2% and 60.3% at 5 and 10
      years, respectively. During follow-up, 80% of patients were asymptomatic. Nearly
      a half of patients required antianginal therapy (monotherapy in 65.7% of them).
      Factors associated with absence of mortality infarction or revascularisation
      were: female sex, absence of restenosis and less severe stenosis before
      angioplasty. Using a multivariate analysis, only the degree of stenosis was
      correlated to the absence of these complications.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8274059
TI  - [Immediate and long-term results of coronary transluminal angioplasty in patients
      under 35 years of age].
AB  - Over an eleven year period, 57 patients under 35 years of age underwent
      percutaneous transluminal coronary angioplasty (PTCA). The features of the study
      population were: 55 men and 2 women, average age 32 +/- 3 years; unstable angina
      in 30%, previous myocardial infarction in 53%, average left ventricular ejection
      fraction 59 +/- 12%, single vessel disease in 84%. A total of 63 vessels were
      dilated. The primary success rate was 81% (72% in the first 29 patients compared
      with 89% in the latter 28 patients, p = 0.1). The following complications were
      observed: peri-procedural infarction (4 cases), emergency coronary bypass surgery
      (4 cases), no fatalities. During follow-up (average 6 +/- 3 years), of the 43
      patients who underwent control coronary angiography in the last 6 months, 14
      (33%) had angiographic restenosis. The long-term outcome was marked by 5 coronary
      bypass operations (3 for restenosis, 1 after failure of PTCA and 1 for
      progression of the coronary disease), 8 PTCAs for a new lesion due to progression
      of the coronary disease, 2 deaths and 2 non-lethal infarctions. The 10 year
      survival was 96 +/- 3% and the survival rate without cardiac events (infarction,
      surgical revascularisation or repeat PTCA) was 62 +/- 10% at 10 years. Of the 54
      survivors, 50 (92%) have no angina, and 44 (81%) continue to take antiischaemic
      drug therapy. Of the 50 patients who were in full employment, 37 (74%) have gone
      back to full-time working and 8 (16%) have taken part-time jobs. (ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8274060
TI  - [Effects of intracoronary injection of SIN-1 on vasoconstriction of epicardial
      arteries induced by acetylcholine].
AB  - Linsidomine or SIN-1, a vasodilator of epicardial arteries, is the active
      metabolite of Molsidomine which is regularly used for intracoronary injection.
      Although its vasodilatory action has been demonstrated on the large coronary
      vessels, it is not known whether this molecule can vasodilate epicardial coronary
      arteries which have been vasoconstricted with acetylcholine. Twelve patients with
      left anterior descending artery (LAD) disease were studied. Intracoronary flow
      velocity was measured with a Doppler catheter (Millar) placed in the proximal
      segment of the LAD and the diameter of the artery was evaluated by quantitative
      angiography. After recording the basal haemodynamic parameters, 12 mg of
      papaverine were injected into the left main coronary artery. After regaining the
      basal state, three incremental doses of acetylcholine (5 x 10(-7), 1(-6) and 5 x
      10(-6) M) were selectively injected into the LAD over a 3 minute period for each
      injection. Then, during continuous infusion of 5 x 10(-6) of acetylcholine, 1 mg
      of SIN-1 was injected in a bolus into the left coronary ostium. After the
      papaverine, the coronary flow velocity increased by 199 +/- 8% associated with a
      vasoconstrictive tendency in the proximal and distal segments of the LAD (NS). In
      response to acetylcholine a dose-dependent vasoconstriction vas observed
      attaining 50 +/- 21% at the last injection in the distal segment of the LAD (p <
      0.001). After an initial increase in coronary flow velocity of 46 +/- 11% (p =
      0.004) and of 26 +/- 11% (p < 0.05) after the first two doses of acetylcholine,
      it decreased after the final injection to close to basal values (NS).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8274061
TI  - [Cardiac arrest reversed: causes and treatments].
AB  - The aim of this study was to report the probable mechanism of resuscitated
      cardiac arrest without acute myocardial infarction. Fifty-seven cases were
      recensed but the arrest was only documented in 44 subjects. Systematic non
      invasive investigations and programmed stimulation showed that the diagnosis of
      cardiac arrest was probably false in 5 patients and, in the others, that a
      ventricular arrhythmia was probably the cause (63%). The occurrence of cardiac
      arrest under antiarrhythmic therapy may reveal an underlying abnormality
      requiring specific therapy (3/8). The absence of cardiac disease did not exclude
      the risk of VF (3 cases). When reproducible, ventricular arrhythmias were present
      during programmed stimulation, the prognosis was good if the arrhythmia could not
      be induced under antiarrhythmic therapy. It was easier to find an effective
      treatment for inducible ventricular fibrillation-flutter (13/17) than for
      inducible ventricular tachycardia (7/17). The prognosis was poor if the
      arrhythmia was unchanged during programmed stimulation under antiarrhythmic
      therapy and non-pharmacological treatment was required.

PMID- 8274062
TI  - [Acute effects of nicardipine on the vascular reactivity of oxygen in patients
      with respiratory insufficiency and pulmonary hypertension].
AB  - Pulmonary vascular response to the inhalation of various concentrations of oxygen
      (FIO2) was studied under basal conditions and after nicardipine in 10 patients
      with pulmonary hypertension secondary to chronic bronchitis. Hemodynamic data and
      blood gases were measured during inhalation of 3 gas mixtures: hypoxia (FIO2 =
      0.15), normoxia (FIO2 = 0.21) and hyperoxia (FIO2 = 0.30). Each gas mixture was
      administered for 20 minutes, initially during an infusion of placebo and then of
      nicardipine giving a steady plasma concentration of 29 +/- 4 ng/ml. This was
      obtained by continuous I.V. infusion of 0.06 mg/kg/hour. Under basal conditions
      with placebo, the heart rate, cardiac output and pulmonary hypertension increased
      with decreasing concentrations of inhaled oxygen. The systemic blood pressure was
      unchanged with hypoxia but decreased during hyperoxia. Nicardipine increased the
      heart rate and the cardiac output but reduced the blood pressure with every
      inhaled oxygen mixture. The blood pressure was independent of FIO2 and the
      reduction observed during hyperoxia with placebo no longer occurred with
      nicardipine. However, the pulmonary hypertension was unaffected. At the dosage
      used in this study, nicardipine modified the systemic vascular response to oxygen
      but not the pulmonary vascular response. The vasodilation induced was much
      greater in the systemic than in the pulmonary circulation. In relation to the
      absence of significant pulmonary vasodilation, no changes in blood gases, due to
      a possible pulmonary shunting effect, were observed. At this dosage, nicardipine
      is ineffective in reducing pulmonary hypertension. However, its systemic
      hypotensive action may be used in patients with respiratory failure due to
      chronic bronchitis without deleterious effects on blood gases.

PMID- 8274063
TI  - [Ablation of accessory pathways by radiofrequency current. Towards a simplified
      approach of Wolff-Parkinson-White syndrome?].
AB  - From December 1990 to April 1992, 41 consecutive patients (22 men and 19 women
      with an average age of 35 +/- 16 years -6-72) underwent ablation of accessory
      atrioventricular conduction pathways (Bundles of Kent) for poorly tolerated
      and/or medically resistant supraventricular tachycardias. In 33 cases, the
      arrhythmia was a paroxysmal SVT, in 7 cases atrial fibrillation, and in 1 patient
      incessant junctional tachycardia causing left ventricular dysfunction. The Wolff
      Parkinson-White syndrome was apparent in 30 patients and concealed in 11 cases.
      The location of the Kent bundle was left lateral in 22 cases (53.7%), posterior
      paraseptal in 9 cases (21.9%), right lateral in 5 cases (12.2%) and anterior
      paraseptal in 5 cases (12.2%). The Kent bundles were ablated by radiofrequency
      currents in 38 cases (92.7%); in 2 patients (4.9%) in whom radiofrequency could
      not be used (increased impedance) high energy electrical shock was successful. In
      one patient (2.4%), it was not possible to suppress the Kent bundle. A single
      session of radiofrequency ablation was sufficient in 33 cases: 7 cases (17.5%)
      required 2 (4) or 3 (3) sessions. The average number of sites of application per
      patient was 8.8 +/- 8.8. The duration and intensity were respectively 32.2 +/-
      9.3 (5-60) seconds and 25 +/- 15 (20-30) watts. With an average follow-up of
      tachycardia or of ventricular preexcitation have been observed in the 40
      patients. In addition, in 36 patients, electrophysiological control studies
      confirmed the initial result with absence of any disturbance of nodohisian
      conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274064
TI  - [Effects of ultrasonic energy on blood clots in vitro].
AB  - Ultrasound may be used to dissolve arterial and venous thrombi. Its effects
      depends on the mode of ultrasonic vibration and on the length of the guide wire.
      The authors studied the in vitro effects of an ultrasonic angioplasty device
      coupled with a 130 cm long titanium flexible guide wire. The system comprises an
      automatic scanning function to determine the optimal frequency of resonance and
      works in the continuous mode of emission. Sixteen thrombi were studied of which 8
      were acellular and 8 whole blood. In each group, 4 were treated in association
      with streptokinase and 4 by ultrasound alone. The ages of the thrombi in each
      subgroup were 1, 3, 7 and 15 days. All the thrombi were dissolved in 6 minutes or
      less (3'15" +/- 1'35") at an average optimal frequency of resonance of 19,444 Hz.
      Ninety six per cent of the debris had a diameter less than 10 microns. Less than
      1% of the debris had a diameter larger than 100 microns. These large particles
      were observed in cellular thrombi and were almost completely absent in dissolved
      acellular thrombi. They were very fragile. The dissolution of the thrombi was not
      accelerated by the association of streptokinase. The ultrasonic energy did not
      induce D-dimer production and its action was probably due to cavitation.
      Ultrasonic energy could provide an alternative treatment for thrombotic vascular
      occlusion provided that more flexible guide wires could be designed.

PMID- 8274065
TI  - [Simultaneous thrombosis of the left anterior interventricular and right coronary
      arteries in a 27 year-old patient with protein S deficiency].
AB  - The authors report a case of myocardial infarction in a 27 year old patient by
      simultaneous thrombosis of the left anterior descending and right coronary
      arteries in an angiographically normal coronary circulation. The young age of the
      patient, the absence of the usual risk factors and a normal angiographic network
      after arterial recanalisation by angioplasty led to the search for a risk factor
      of thrombosis. This showed a qualitative deficiency of protein S and the absence
      of any other abnormality of coagulation or fibrinolysis. This case raises the
      question of a causal relationship between a hereditary protein S deficiency and
      thrombotic arterial occlusion.

PMID- 8274066
TI  - [Bacterial vegetation on a permanent endocavitary stimulation probe. Apropos of a
      case].

PMID- 8274067
TI  - [Myxoma of the tricuspid valve. Apropos of a case].
AB  - The authors report the case of a chance echocardiographic finding of a tricuspid
      valve myxoma. Transesophageal echocardiography provided valuable complementary
      information concerning the precise location of the tumour. Tricuspid valve myxoma
      is a very rare condition: a review of the literature recensed 16 other cases.
      This case is of particular interest because of the associated pathological signs:
      erythemato-papular skin lesions which regresses after ablation of the tumour and
      a multinodular goitre with a cold isthmic nodule which raised the possibility of
      the diagnosis of Carney's complex.

PMID- 8274068
TI  - [Successful pregnancy after Fontan procedure complicated by recurrent junctional
      tachycardia].
AB  - A woman had a successful pregnancy with a normal delivery at 33 weeks seven years
      after a modified Fontan procedure for tricuspid atresia. This pregnancy was
      associated with aggravation of attacks of junctional tachycardia which became
      symptomatic and recurrent despite prescription of several antiarrhythmic agents.

PMID- 8274069
TI  - [Can the molecular biology of pharmacy be expanded?].

PMID- 8274070
TI  - New 4-amino-7,8-dimethoxy-5H-pyrimido[5,4-b]indole derivatives: synthesis and
      studies as inhibitors of phosphodiesterases.
AB  - A series of 4-amino-7,8-dimethoxy-5H-pyrimido[5,4-b]indole derivatives has been
      synthesized. These compounds resemble carbazeram and other pyridazino compounds
      with activity in the cardiovascular system. Some of these new compounds possess
      inotropic activity (Table 2), with a complementary effect on the inhibition of
      different CGI-PDE (Table 3). The most active compounds 5, 6d, and 7 also possess
      activity as vasodilators (Table 4). Some of these new compounds inhibit blood
      platelet aggregation induced by ADP and AA and are active as inhibitors of human
      platelet PDEs (Tables 5 and 6).

PMID- 8274071
TI  - Selectivity of sterically fixed tryptamine and 5-methoxytryptamine derivatives
      for serotonin receptor subtypes, II: Structure-activity relationships and in
      vitro pharmacology of N-alkyl- and N,N-dialkyl-3- indolylbicyclo-[2.2.1]-heptane
      2-amines.
AB  - Twenty-four norbornane analogues of tryptamine and 5-methoxytryptamine were
      investigated for affinity at 5-HT2 receptors of the rat tail artery and proved to
      be weak non-competitive antagonists of 5-HT. Compound 12 which displayed a marked
      depression of the concentration-effect curves, was examined for potential
      interaction with the allosteric binding site of the 5-HT2 receptor. The effects
      elicited by 12, in the presence and absence of the allosteric activator
      ketanserin, were atypical and must be attributed to a mechanism, unknown up to
      now. In radioligand displacement experiments binding data for a set of nine
      compounds were determined at 5-HT1-like, 5-HT2 and 5-HT3 receptors, indicating
      subtype selectivity for some analogues. The binding affinity of 8 at 5-HT3
      receptors which was comparable with the affinity of the selective 5-HT3 agonist 2
      methyl-5-HT, could not be demonstrated on the longitudinal muscle strip of the
      guinea-pig ileum, partially due to the M3 antimuscarinic activity of 8.
      Functional studies on the rat oesophageal tunica muscularis mucosae did not
      reveal 5-HT4 agonist properties for two analogues of 5-methoxytryptamine (8, 16).

PMID- 8274072
TI  - Lactones, XXVII: "Lactonized" pimocide--stability and dopamine receptor affinity
      of its enantiomers and ring open derivatives.

PMID- 8274073
TI  - Dengue. Muscle biopsy findings in 15 patients.
AB  - Dengue is known to produce a syndrome involving muscles, tendons and joints. The
      hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash,
      and headache. The neuromuscular aspects of this infection are outlined only in
      isolated reports, and the muscle histopathological features during myalgia have
      not been described. In order to ascertain the actual neuromuscular involvement in
      dengue and better comprehend the histological nature of myalgia, we performed a
      clinical and neurological evaluation, a serum CPK level and a muscle biopsy (with
      histochemistry) in 15 patients (4 males), median age 23 years (range 14-47) with
      classic dengue fever, serologically confirmed, during the brazilian dengue
      epidemics from September 1986 to March 1987. All patients had a history of fever,
      headache and severe myalgia. Upon examination 4 had a cutaneous rash, 3 had
      fever, and 3 a small hepatomegaly. The neurological examination was unremarkable
      in all and included a manual muscle test. CPK was mildly elevated in only 3
      patients. Muscle biopsy revealed a light to moderate perivascular mononuclear
      infiltrate in 12 patients and lipid accumulation in 11. Mild mitochondrial
      proliferation was seen in 3, few central nuclei in 3, rare foci of myonecrosis in
      3, and 2 patients had type grouping. Dengue in our patients, produced myalgia but
      no detectable muscle weakness or other neuromuscular involvement. The main
      histopathological correlation with myalgia seems to be a perivascular mononuclear
      infiltrate and lipid accumulation.

PMID- 8274074
TI  - Midazolam daytime residual effect evaluated by the Multiple Sleep Latency Test.
AB  - Daytime sleepiness after ingestion of midazolam as a hypnotic was quantitatively
      studied employing the Multiple Sleep Latency Test (MSLT). We evaluated 20 healthy
      volunteers, 10 of which received a single oral dose of midazolam (15 mg, one
      tablet) and 10 of which received placebo, in a double-blind design. Tablets were
      administered at 2200 h, bedtime. On the following day, all subjects were
      submitted to a clinical evaluation, a subjective checklist and the MSLT. The mean
      age was 34.7 +/- 8.9 years in the midazolam and 38.0 +/- 10.6 years in the
      placebo groups (n.s.). Sex and weight distributions were similar in both groups
      (n.s.). Clinical evaluation and subjective symptom checklist did not make evident
      significant differences between midazolam and placebo groups (n.s.). The MSLT was
      performed at 0900, 1100, 1300, 1500 and 1700 h. Mean sleep latencies were 12.0,
      12.7, 8.0, 13.5, 17.0 min in the midazolam group; mean sleep latencies were 13.8,
      9.0, 6.9, 9.5, 13.6 min in the placebo group (n.s.). In the single dose, double
      blind design here evaluated, midazolam did not show differences in relation to
      placebo on the following day, detectable by the MSLT.

PMID- 8274075
TI  - Electroencephalogram base rhythm in AIDS patients.
AB  - We studied the EEG of 73 patients diagnosed with HIV infection, with or without
      secondary complications. Sixty-eight belonged to CDC (Center for Disease Control)
      group IV and 38 presented signs or symptoms of encephalic neurological
      impairment. Rhythms constituting base activity were alpha (65.75%), beta
      (13.70%), theta (12.33%), and delta (8.22%). The alpha rhythm presented two
      modes: slow (8 to 9 Hz) in 25/48 or 52.08% of the cases and not-slow (> 9 to 13
      Hz) in 23/48 or 47.92% of the cases. The alpha slow-mode has been observed in
      about 10 to 15% of the normal population, with the 8 Hz frequency being found in
      only 1% of the normal adult population, which suggests that in some manner HIV is
      implicated in the slowing-down of the EEG base rhythm in AIDS patients. The
      patients from CDC group IV with encephalic neurological involvement presented a
      base rhythm significantly lower than those with non-encephalic involvement or the
      absence of neurological impairment.

PMID- 8274076
TI  - [Alzheimer's disease. Relationship between time of disease and its staging].
AB  - Forty-nine patients with clinical diagnosis of Alzheimer's disease were submitted
      to neuropsychological evaluation for staging the disease. The time of the initial
      symptoms was correlated to the stage of the disease. The evolution was protracted
      in 28.5% of the patients with only insidious memory deterioration. For another
      group of patients (12.2%) the evolution was serious since the beginning of the
      disease, with apraxo-agnosic signs. For the 34 patients with apraxo-agnosic
      impairment, in 50% this manifestation began in the first two years of the
      disease. Data suggest the occurrence of two subgroups. In the first the evolution
      of the disease is rapid, and in the second it is protracted. Also, they suggest
      that the evolution in the first two years is critical for characterizing the
      severity of progression in the clinical manifestations of Alzheimer's disease.

PMID- 8274077
TI  - [Neurologic evaluation of 118 patients in the first postoperative period of
      cardiovascular surgery].
AB  - 118 patients (79 mean and 39 women, mean age of 50.7 years) who underwent
      cardiovascular surgery and extracorporeal oxygenation were prospectively
      evaluated for neurologic complication and its correlation with risk factors. 71
      were submitted to coronary artery graft by-pass (RM), 18 to valve replacement
      (TV), 6 to prosthetic valve replacement (RV), 11 to commissurotomy(Co), 5 to
      thoracic aortic aneurysm correction (An Ao T) and 7 to other surgeries (OT). All
      of them received extracorporeal oxygenation. No deaths were registered; 14
      (11.9%) patients had neurologic abnormalities: delirium in 7 cases, ischemic
      stroke in 6, epileptic seizure in 3. Patients with systemic arterial hypertension
      and older patients exhibited a statistically significant (p < 0.05) higher risk
      of complication. Compared to data of the literature, we had a lower index of
      morbidity and mortality.

PMID- 8274078
TI  - [Lobar cerebral hemorrhage. Clinical aspects, etiology and course. Review of 58
      cases].
AB  - Fifty eight patients with spontaneous lobar hemorrhage of a 264 patients series
      with intracerebral hemorrhage seen during a six years period are reviewed. Twenty
      nine had arterial hypertension, 9 had other etiologies, and in the remaining 20
      cases no apparent etiology was detected. Headache was a prominent symptom and
      occurred in 56%. Seizures occurred in 12%. Coma was infrequent. Clinical findings
      on admission depended on the location of the hematoma. Lobar hemorrhage occurred
      most commonly in the parietal region. Mortality rate was 8.6%. Size of hematoma
      (larger than 4 cm) on CT and altered consciousness on admission correlated with
      poor outcome.

PMID- 8274079
TI  - [Value of the smear in the peroperative diagnosis of tumors removed in
      neurosurgeries].
AB  - The smear technique has been used for rapid diagnosis of tumors removed in
      neurosurgeries in many neuropathological centers. In order to assess the
      diagnostic accuracy of this technique, we examined 137 smears and made a
      cytohistological correlation. Our cases include 12 astrocytomas, 4 anaplastic
      astrocytomas, 26 glioblastomas, 7 oligodendrogliomas, 5 medulloblastomas, 8
      schwannomas, 17 meningiomas, 13 pituitary adenomas, 20 metastatic tumors and 18
      assorted tumors and non neoplastic lesions. The correct diagnosis was made in
      91.2% of the cases which coincides to the literature. The knowledge of the
      localization and the characteristic morphologic features of some tumors were
      important for the diagnosis. The ability to recognize normal nervous tissue in
      smears was important even to help the surgeon to reach the tumor. We believe that
      the use of smears should be encouraged in our country in view of the simplicity
      of its preparation and accuracy of results.

PMID- 8274080
TI  - [Cytologic aspects of intracranial and spinal canal tumors].
AB  - We present the cytologic aspects of 137 tumors operated by neurosurgeons,
      including 12 astrocytomas, 4 anaplastic astrocytomas, 26 glioblastomas, 7
      oligodendrogliomas, 5 medulloblastomas, 8 schwannomas, 17 meningiomas, 13
      pituitary adenomas, 20 metastatic tumors and 18 assorted tumors and nonneoplastic
      lesions. We have also analysed cytologically samples of normal nervous tissue
      obtained from autopsies, aiming at its recognition and distinction from the
      neoplastic tissue in biopsies. The tumors were analysed in smears which were
      subsequently compared with the histological sections. Although it is important to
      observe cytological details in the tumor, occasionally cells are arranged in such
      a way, that an overview of the smear practically allows the diagnosis of the
      tumor.

PMID- 8274081
TI  - [Lumbar microdiscectomy. Technique and results in 80 cases].
AB  - The results of treatment for 80 patients with lumbar disc disease who undergone
      microdiscectomy were reviewed. Low rate of post-operative complications, short
      hospital stay and early return of the patients to their normal activities were
      observed.

PMID- 8274082
TI  - [Histoplasmosis of the central nervous system. Clinical aspects in 8 patients].
AB  - Clinical approach has been made in eight patients with histoplasmosis of the
      central nervous system. All patients had no evidence of immunodepression. Time
      disease at diagnosis ranged from 6 to 108 months (median 36 months). Main signs
      and symptoms were: intracranial hypertension in 6 patients; impairment of memory
      in 4; confusion in 4; seizures in 2; urinary incontinence in 2; sexual impotency
      in 1. Meningo-encephalitic form was present in 6 patients, while the
      granulomatous form was found in 2. Diagnostic confirmation was based on: biopsy,
      in 1 case; necropsy, in 2 cases; cerebrospinal fluid (CSF) sediment culture, in
      1; detection of antibodies against Histoplasma capsulatum in the CSF, in 5 cases.
      There was, in all patients, an expressive difference between CSF alterations
      (intense, merging acute and chronic phase elements) and clinical symptomatology
      (patients in general oligosymptomatic).

PMID- 8274083
TI  - [Microanatomy of the cerebellopontine angle with morphometric analysis of the
      internal acoustic meatus].
AB  - Twelve cerebello-pontine angles of the corpses of six adults were dissected with
      the aid of a surgical microscope. The following parameters were analyzed: the
      superior-inferior (vertical) and the anterior-posterior (horizontal) dimensions
      of the internal acoustic meatus (IAM); and the distances from the IAM to the
      Meckel's cave, the superior jugular foramen (SJF) and the inferior jugular
      foramen (IJF). We used a mathematical formula to calculate the area of the IAM.
      Important variations in the IAM's measurements were found, mainly concerning its
      area. This study contributes to a better understanding of cerebello-pontine angle
      (CPA) structures and their relationships with osseous parameters in Brazilian
      individuals.

PMID- 8274084
TI  - [Intraneural distribution of the arteries in the cauda equina of newborn
      infants].
AB  - Mesoscopic study of the irrigation of the lumbosacral segment of the spinal cord
      and the roots of the cauda equina was carried out in corpses of 18 Brazilian
      newborns of either sex. Through the abdominal portion of the aorta nine newborns
      were injected with neoprene latex and the others were injected with a 5% solution
      of gelatin coloured with black Indian ink. The latter were cleared by the
      Spalteholz technique. Two types of arterial distribution were determined: (a)
      proximal and distal radicular arteries supplying the corresponding roots, which
      presented in their middle third an arterial low density, that is, hypo
      irrigation; (b) segmental spinal arteries, varying in number, more frequent on
      the left side and having a larger caliber than that of the radicular arteries,
      accompanying the roots without providing collateral branches to the neural roots
      and anastomosed with the spinal arteries.

PMID- 8274085
TI  - [Anatomic and quantitative study of the human pterygopalatine ganglion.
      Morphometry and stereology].
AB  - The pterygopalatine ganglion is important in the regulation of the intraocular
      pressure and in the cerebral vasodilatation connected with headache of vascular
      origin. Four human ganglia were dissected, fixed in formalin and serially
      sectioned with a 6 microns thickness. The volume of the ganglion was calculated
      by point-counting and stereological parameters were determined using the test
      system M42 with light microscopy. The PG volume was (mean +/- standard error of
      the mean) 5.6 +/- 0.5 mm3. The volume density of neurons was 51.1% +/- 3.4%, and
      the unitary volume of the neurons was 41,200.0 +/- 2,250.0 microns. The numerical
      density was 12,600.0 +/- 677.0 neurons by mm3, therefore approximately 70,560
      neurons by ganglion.

PMID- 8274086
TI  - Breathing frequency in sleep related respiratory disturbances.
AB  - In normal adults, breathing frequency (f) is highly reproducible within an
      individual ranging from 8 to 25 min-1; during sleep, f is known to change only
      minimally. This variable is rarely reported in studies of adults with various
      sleep related respiratory disturbances (SRRD). We occasionally observed a
      spectacular increase of f during sleep in patients with SRRD associated with
      hypopnea and 02 desaturation. We undertook a retrospective study of 650
      consecutive all-night polysomnographic recordings, in order to evaluate how often
      such an increase in breathing frequency occurs and with which factors it is
      associated. We excluded patients with major respiratory failure. We found 16
      patients (11 males; mean +/- SD, age: 45 +/- 13 yrs; body mass index (BMI): 44 +/
      11 kg/m2) with f > 25 min-1 during sleep (tachypneic group, T). We performed a
      one-for-one matching for sex, age and BMI between the T and a control (C) group
      (age: 45 +/- 12 yrs; BMI 44 +/- 10 kg/m2), with similar sleep disturbances but
      normal f during sleep. We compared the f in each vigilance state by averaging
      five measurements of f, each of one minute duration in a stable period. We
      observed that: C patients showed no significant change in f in any vigilance
      state; T patients showed a higher f already during wakefulness (p < 0.05) and f
      increased significantly in all sleep stages (< 0.01). We compared the two groups
      for many clinical and polysomnographic variables.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8274087
TI  - [Sporadic amyotrophic lateral sclerosis. Diagnostic criteria].
AB  - The authors report two cases of amyotrophic lateral sclerosis (ALS) misdiagnosis
      (a craniocervical junction disorder, and a cervical spinal cord ependymoma). They
      review some causes of ALS-like syndrome and propose a protocol to be adopted for
      the study of all patients who present clinical abnormalities suggesting ALS.

PMID- 8274088
TI  - [Extradural hematoma of the posterior fossa. Report of 7 cases].
AB  - Hematomas of the posterior fossa are an uncommon complication of head injury.
      Almost invariably they occur after trauma of the occiput, and are associated with
      skull fracture. Their diagnosis and management have been greatly improved by CT
      scanning. In the present series, the majority of patients had acute evolution
      indicating the potential hazard of conservative treatment. Our results (29%
      mortality) are similar to those previously reported in other series.

PMID- 8274089
TI  - [Multiple meningiomas and neurofibromatosis. Report of 3 cases].
AB  - Multiple intracranial meningiomas (MIM) may be a specific pathological entity. In
      general these lesions are associated with neurofibromatosis. The classical
      clinical picture of neurofibromatosis, as described by von Recklinghausen, may
      not necessarily be associated with MIM. This possibility is a direct result of
      the variable penetrability of chromosomic aberrations connected with the
      chromosome 22. Molecular studies of these tumors confirmed this finding. In our
      series of 108 patients with intracranial meningiomas only three cases were
      multiple. In only one of them external stigmata of von Recklinghausen's disease
      were detected. In the absence of skin manifestations of neurofibromatosis in
      patients with MIM it is very difficult to diagnosis von Recklinghausen's disease,
      and the so called "true multiple meningiomas". The authors believe that there are
      no justificative findings to consider MIM as an independent pathological entity.

PMID- 8274090
TI  - [Cerebral metastasis from prostatic neoplasm simulating meningioma. Report of a
      case].
AB  - The clinical aspects of the meningiomas are well described. However, there is an
      important number of reports on a variety of other lesions simulating meningioma,
      including the prostate cancer. The authors describe one additional patient with
      prostate cancer who at presentation had clinical and radiographic signs
      suggesting meningioma. The literature on the subject is reviewed and summarized.

PMID- 8274091
TI  - [High medular compression caused by neurenteric cyst. Report of a case].
AB  - The authors report the case of a child with a neuroenteric cyst compressing the
      high cervical spinal cord at the level of C1 to C3. The tumor was completely
      excised through a laminotomy with good results. The literature is revised, and
      the embryology, symptomatology, treatment and results are discussed.

PMID- 8274092
TI  - Creutzfeldt-Jakob disease. A case report, with special attention to the
      electroencephalogram in this disorder and to its possible relationships to kuru,
      scrapie and "mad cow disease".
AB  - A case of Creutzfeldt-Jakob disease in a 58-year-old Brazilian cattle rancher and
      businessman is presented. The EEG was normal, which is consistent with the fact
      that it was made during the first half of his illness; in a later stage
      suppression of normal rhythms by slow moderate voltage waves would be expected.
      The resemblances of kuru, scrapie and "mad cow disease" to C-J disease are
      discussed. In each of these 4 illnesses the patient or affected animal (scrapie
      and "mad cow disease") (a) has a widespread spongiform encephalopathy and
      consequent dementia, myoclonic epilepsy and cerebellar and corticospinal
      symptoms. (b) Each illness is caused by a virus (or virus-like organism called a
      PrP or prion) which is unusually resistant to heat and entirely resistant to
      ultraviolet light and x-rays. (c) This causative agent can be transmitted to
      other mammals by intracerebral injection or, in the proved cases of 3 of them, by
      the oral route. Unresolved questions about C-J disease include the following: Are
      C-J disease, kuru, scrapie and "mad cow disease" essentially similar illnesses
      caused by the same virus or by subtle variants of it? What is the incubation
      period of C-J disease, and does its virus exist for long periods of time in some
      asymptomatic persons, some of whom may never become neurologically ill? How does
      this virus enter the bodies of most persons with C-J disease, and why does the
      clinical disease characteristically occur only in middle age?

PMID- 8274093
TI  - Chorea as a sign of systemic lupus erythematosus activity. Case report.
AB  - Chorea may occur as a neurological manifestation of systemic lupus erythematosus
      and is often associated with detection of antiphospholipid antibodies. No
      evidence of chorea as a sign of lupus activity has been established. We describe
      a patient with systemic lupus erythematosus associated with antiphospholipid
      antibodies who developed chorea, which has been considered a sign of lupus
      activity.

PMID- 8274094
TI  - Hypothalamic tumor associated with atypical forms of anorexia nervosa and
      diencephalic syndrome.
AB  - We report the case of a 10-year-old girl with a mature teratoma in the
      hypothalamic region. The patient presented a 2-month history of anorexia, psychic
      disturbances and a 37% loss of body weight. These symptoms had led initially to a
      diagnosis of major depression and atypical anorexia nervosa. She also presented
      some signs and symptoms of diencephalic syndrome. This case illustrates the
      importance of considering a slow-growing mass as a rare but real possibility in
      the differential diagnosis of anorexia nervosa, mainly in atypical cases.

PMID- 8274095
TI  - Cerebral metastasis from choriocarcinoma and oncotic aneurysms. Case report.
AB  - Cerebral metastasis occur in 10 to 20% of patients with choriocarcinoma. We
      describe the twelfth patient with oncotic aneurysms from choriocarcinoma verified
      by cerebral angiography. The importance to consider this disease in a woman of
      childbearing age who develop an intracerebral hemorrhage or a lesion with mass
      effect is emphasized, as well as laboratial and radiological characteristics.
      Therapeutic approaches with chemotherapic agents, surgery and irradiation are
      discussed.

PMID- 8274096
TI  - [Brown-Sequard syndrome in schistosomiasis. Report of a case].
AB  - The authors report a case of schistosomiasis mansoni with intraspinal
      localization on a 39 year old man who presented neurologic manifestation likely a
      Brown-Sequard syndrome. Cerebrospinal fluid examination showed positive
      immunofluorescent test for schistosomiasis, and treatment was started at once.

PMID- 8274097
TI  - Therapeutic effects of flunitrazepam in dystonias and torticollis. Preliminary
      communication.
AB  - A new form of clinical treatment is proposed for dystonias and torticollis using
      flunitrazepam (FN), a powerful agonist of all benzodiazepine receptors of GABA
      neurons. FN has a specific effect in dystonic patients, specially those in which
      the hypnotic effect of this drug is absent or diminished, thus suggesting the
      existence of two different neurochemical categories of dystonias.

PMID- 8274098
TI  - Preservation of the medical centers of excellence.

PMID- 8274099
TI  - Artificial heart: past, present, and future.

PMID- 8274100
TI  - Peritoneal dialysis for the removal of protein-bound markers of hepatic
      insufficiency.
AB  - The addition of human serum albumin (HSA) to peritoneal dialysate increases the
      clearance of bilirubin in rats suffering from obstructive jaundice. The acceptor
      properties of the fluid can be enhanced by using HSA that does not contain
      standard stabilizing additives and has been purified by further adsorption on
      activated carbon. Bilirubin-containing dialysate fluid, as well as the ascitic
      fluid of cirrhotic patients, can be regenerated by a combination of membrane
      ultrafiltration and carbon adsorption. These observations suggest a potentially
      useful scheme for continuous, regenerative peritoneal dialysis in the treatment
      of hepatic insufficiency.

PMID- 8274101
TI  - Granulocyte superoxide anion and elastase release during cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) is known to induce several pathogenic responses in
      cardiovascular surgery. To explore leukocyte activation during PCB, we
      investigated superoxide anion (O2-) production by granulocytes in 6 patients
      undergoing aortocoronary bypass surgery. O2- production was determined with
      chemiluminescence amplified by a cypridina luciferin analogue. Granulocytes
      collected from the blood in the arterial site of the CPB circuit were stimulated
      by phorbol myristate acetate, n-formyl-methionyl-leucyl-phenylalanine, and
      opsonized zymosan. All the stimulators failed to disclose a significant
      difference between the magnitude of chemiluminescence during and after CPB.
      However, significant complement activation was detected, and the plasma level of
      granulocyte elastase increased gradually during and after CPB. This discrepancy
      between the unchanged O2- production by stimulated granulocytes and the increase
      in inflammatory mediators including granulocyte elastase may be due to
      sequestration of activated granulocytes in extravascular tissues. Namely, it was
      highly likely that activated granulocytes responsible for the increased plasma
      elastase level were sequestered and remained outside the blood circulation.

PMID- 8274102
TI  - Evaluating the flow characteristics of artificial pumping devices using nuclear
      scintigraphy.
AB  - The design and development of artificial blood pumps require qualitative and
      quantitative data relative to pump filling, ejection, and wall motion in order to
      optimize the design and maximize the pattern of blood flow through the pump. To
      assist in the development of an artificial heart, we utilized radionuclide
      scintigraphy and a high-resolution gamma camera to evaluate the flow patterns
      through the pump. We performed a comparative analysis of the flow patterns in a
      pneumatically driven ventricular assist device (Sarns/3M VAD) and the
      electrically driven Milwaukee Heart. These analyses disclose some significant
      differences between the two devices with regard to the blood sac compression
      patterns and ejection as well as valvular regurgitation. On the basis of these
      findings, nuclear scintigraphy for analyzing fluid shear stress and flow dynamics
      seems a useful technique for evaluating blood flow through artificial blood
      pumps. Because the procedure does not require a translucent casing or direct
      contact with the device being studied, it would be especially useful in
      evaluating artificial blood pumps implanted in patients with heart failure.

PMID- 8274103
TI  - Plasmapheresis: historical perspective, therapeutic applications, and new
      frontiers.

PMID- 8274104
TI  - The development of a safe and highly durable balloon catheter for the IAB.

PMID- 8274105
TI  - Is heparin really indicated in bacterial meningitis?

PMID- 8274106
TI  - Survival in amyotrophic lateral sclerosis. The role of psychological factors.
AB  - OBJECTIVE: Examining the relationship between psychological status and survival
      in amyotrophic lateral sclerosis. Our hypothesis is that psychological distress
      is associated with greater mortality and shorter survival time than psychological
      well-being. DESIGN: Cross-sectional, longitudinal. The baseline evaluations used
      were disease severity and 10 psychometric tests. A psychological status score was
      derived from these tests. Survival status was monitored for 3.5 years.
      Interviewers were blinded to other interviews and data analysis. SETTING:
      Patient's residence. PATIENTS: The criteria for eligibility were diagnosis of
      amyotrophic lateral sclerosis by a neurologist, dementia or alcoholism absent,
      communication in English, and any severity or length of disease. It was a
      volunteer sample consisting of 144 patients from amyotrophic lateral sclerosis
      clinics or community-based amyotrophic lateral sclerosis support groups. In this
      sample 66% were men, 94% were white, mean age at diagnosis was 55 years, 79% were
      married, 60% had some college education, and 61% died during the study.
      INTERVENTIONS: None. MAIN OUTCOME MEASURES:  END POINTS: mortality during study,
      survival time from intake to last follow-up. RESULTS: Comparison between high and
      low psychological score groups: 32% of high and 82% of low died; survival curves
      were significantly different. Controlling for confounding factors (length of
      illness, disease severity, age), patients with psychological distress had a
      greater risk of mortality (relative risk, 6.76; 95% confidence limits, 1.69 to
      27.12) and greater likelihood of dying in any given time period (relative risk,
      2.24; 95% confidence limits, 1.08 to 4.64) than those with psychological well
      being. CONCLUSION: Adjusting for confounding factors, psychological status is
      strongly related to outcome in amyotrophic lateral sclerosis. Further studies on
      psychological status should be done to confirm its prognostic value.

PMID- 8274107
TI  - Normal activation of frontotemporal language cortex in dyslexia, as measured with
      oxygen 15 positron emission tomography.
AB  - OBJECTIVE: To assess the ability of dyslexic men to activate left middle to
      anterior language cortex normally. DESIGN: Positron emission tomography using
      oxygen 15-labeled water as a tracer during rest and during a syntax task
      involving sentence comprehension. SETTING: Research hospital. PATIENTS OR OTHER
      PARTICIPANTS: Fifteen right-handed, severely dyslexic men (mean [+/- SD] age, 27
      +/- 5 years) and 20 matched controls. INTERVENTIONS: None. MAIN OUTCOME MEASURE:
      Cerebral blood flow. RESULTS: During rest, dyslexics showed reduced blood flow
      (relative to controls) in one left parietal region near the angular/supramarginal
      gyri, but otherwise normal flow. During syntactic processing, dyslexics and
      controls showed similar, significant activation of left middle to anterior
      temporal and inferior frontal cortex. CONCLUSIONS: These results, together with
      the previously reported failure of dyslexics to activate left temporoparietal
      cortex during phonologic processing, argue for dysfunction of left cortical
      language areas restricted to posterior language regions in dyslexia.

PMID- 8274108
TI  - Severe impairment battery. A neuropsychological test for severely demented
      patients.
AB  - OBJECTIVE: Patients with progressive dementia invariably evolve to a stage where
      they can no longer be tested by standard neuropsychological tests. We studied the
      use of the Severe Impairment Battery (SIB) in such patients. DESIGN: Case series.
      SETTING: Geriatric long-term facility. PATIENTS: Sixty-nine patients who met the
      criteria of the Diagnostic and Statistical Manual for Mental Disorders, Revised
      Third Edition, for dementia were selected. The diagnosis of probable Alzheimer's
      disease was established according to the guidelines suggested by the National
      Institute of Neurologic and Communicative Diseases and Stroke/Alzheimer's Disease
      and Related Disorders Association. There were 18 men and 51 women. The mean age
      of the population was 82.99 +/- 5.66 years. The mean Mini-Mental State
      Examination (MMSE) score was 10.71 +/- 6.14. MAIN OUTCOME MEASURE: To
      characterize the cognitive profile and evolution of severely demented patients by
      means of the SIB. RESULTS: The mean score on the SIB was 92.52 +/- 31.92, with a
      possible maximum of 133 points. Subgroups of patients with the most severe degree
      of dementia (MMSE scores of 0 to 5 and 6 to 11) showed significant differences in
      their scores on the SIB. In contrast, no differences were found between subgroups
      with MMSE scores of 6 to 11, 12 to 17, and greater than 17. Fifteen patients who
      had MMSE scores of less than 6 had SIB scores ranging from 7 to 81. All cognitive
      domains showed a deterioration across the four severity groups as determined by
      the MMSE scores and also during a longitudinal study performed on 26 patients.
      CONCLUSION: Our study indicates that the SIB is useful for the neuropsychological
      evaluation of severely demented patients and for their follow-up.

PMID- 8274109
TI  - Effect of diagnostic testing for multiple sclerosis on patient health
      perceptions. Rochester-Toronto MRI Study Group.
AB  - BACKGROUND AND METHODS: We examined the effect on health perceptions of a
      diagnostic workup in 172 patients with suspected multiple sclerosis (MS) using
      two questionnaires (Mishel, Rand Medical Outcome Study) and three visual analogue
      scales measuring distress. Patients were categorized into "MS," "not MS," or
      "still uncertain" groups. RESULTS: Patients with a definitive diagnosis reported
      a significant decrease in uncertainty (analysis of variance [ANOVA] P = .0004).
      The Medical Outcome Study showed a slightly worsened perceived current health
      status (ANOVA P = .02) and future health outlook (ANOVA P = .001) in the MS group
      compared with the other two groups. Distress over physical symptoms decreased in
      all three groups and anxiety was more likely to decrease than increase even in
      those with MS. Prognostic uncertainty distress decreased in the not MS group and
      still uncertain groups, whereas it remained unchanged in the MS group (P =
      .9156). CONCLUSION: Significant and generally beneficial changes in patient
      health perceptions are seen associated with a neurologic workup in suspected MS,
      irrespective of the final diagnosis.

PMID- 8274110
TI  - A randomized trial of test result sequencing in patients with suspected multiple
      sclerosis. Rochester-Toronto MRI Study Group.
AB  - BACKGROUND AND METHODS: We performed a randomized trial of the incremental impact
      of high-volume contrast computed tomographic scan of the brain plus trimodal
      evoked potentials vs magnetic resonance imaging of the brain on neurologists'
      diagnostic labeling of patients with suspected multiple sclerosis (MS). Two
      hundred and four patients with suspected MS (clinically possible 59% or probable
      41%-McAlpine criteria) were assessed by two neurologists. Patients were
      diagnostically categorized after reviewing the results of the tests presented in
      random order. RESULTS: Most of the change in diagnostic categorization occurred
      after presenting the first test result irrespective of result sequence (chi 2 =
      0.01, P = .99). The diagnoses became more definitive when all test results were
      available (P < .001). Magnetic resonance imaging and evoked potential were
      suggestive of MS equally frequently (chi 2 = 0.57, P = .45). CONCLUSION: In
      suspected MS, there is no difference in diagnostic effect between brain magnetic
      resonance image scanning and computed tomography plus trimodal evoked potentials.

PMID- 8274111
TI  - Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance
      imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group.
AB  - OBJECTIVE: Magnetic resonance imaging, computed tomography, cerebrospinal fluid
      analysis, and evoked potential testing are used to assist in the diagnosis of
      patients suspected to have multiple sclerosis (MS). The impact of these tests on
      a clinician's diagnosis of patients suspected to have MS has not been studied
      systematically. DESIGN: Clinicians made a diagnosis of each patient following
      clinical evaluation, again after reviewing the results of magnetic resonance
      imaging, and finally after reviewing information from other laboratory testing.
      These diagnoses were compared with the criterion standard of a masked "gold
      standard" panel reviewing all information after a mean follow-up of 0.9 year.
      SETTING: The General Neurology Clinic and Multiple Sclerosis Clinic of the
      University of Rochester (NY). PATIENTS: A consecutive sample of 62 patients
      diagnosed as having either possible or probable MS following clinical evaluation.
      MAIN OUTCOME MEASURE: Changes in diagnostic certainty of clinicians following
      incremental presentation of new laboratory data and the accuracy of such
      diagnoses. RESULTS: Clinicians used magnetic resonance imaging findings to
      diagnose definite MS or to eliminate MS from diagnostic consideration in 44% of
      cases. In these cases, further laboratory testing did not alter clinicians'
      decisions. In the remaining 56% of cases, in which magnetic resonance imaging did
      not lead to a diagnosis of definite MS or eliminate MS from diagnostic
      consideration, further laboratory testing led to such diagnoses in an additional
      13% of cases. Gold standard diagnoses were in agreement with the clinician's
      assessments. CONCLUSIONS: Magnetic resonance imaging aids in the evaluation of
      patients suspected to have MS; other subsequent studies (computed tomography,
      cerebrospinal fluid analysis, and evoked potential testing) have less impact.
      After all studies are performed, about half of such patients still have a
      tentative diagnosis.

PMID- 8274112
TI  - The value of diagnostic information to patients with suspected multiple
      sclerosis. Rochester-Toronto MRI Study Group.
AB  - OBJECTIVE: To determine the value of diagnostic information to patients with
      suspected multiple sclerosis (MS). Because treatment choices would be only
      minimally affected by earlier diagnosis for most patients with this clinical
      problem, this study assessed the "nondecisional" value of diagnosis. DESIGN:
      Prospective survey of patients before and after diagnostic workup, including
      imaging with magnetic resonance scanning. We assessed the effect of diagnostic
      information on patients' sense of well-being, as well as direct measures of the
      utility of information (using time trade-off and willingness-to-pay techniques).
      SETTING: Patients referred from primary care practices for diagnostic workup for
      suspected MS to neurology clinics and practices. PATIENTS: Sixty-eight
      individuals, mean age 37.5 years, 53 female and 15 male. Thirty-one patients were
      classified as having "probable MS," and 37 were classified as having "possible
      MS" by the examining neurologist before workup. MEASUREMENTS: Present and future
      health perception, uncertainty about diagnosis-prognosis, and level of anxiety.
      Willingness to pay for diagnostic information, quality of life as measured by the
      time trade-off technique, and psychological state of the patient before and after
      diagnosis. RESULTS: Diagnostic uncertainty fell significantly as a result of the
      diagnostic workup. Most patients (59/62) said that they were better off having
      received diagnostic information. Although anxiety seemed to be reduced by
      testing, overall anxiety levels did not decrease as much as anticipated. Patients
      also became less optimistic about their future health after testing. On average,
      patients were willing to forgo 4.5 quality-adjusted life days to receive an
      earlier diagnosis and their quality of life after diagnosis improved slightly.
      Subgroups of patients differed in their response to diagnostic information. Those
      in whom no definitive diagnosis emerged tend to be more anxious rather than being
      reassured by the "negative" workup. Individuals with "positive" workups became
      less anxious and expressed favorable feelings about the diagnostic workup even
      though they often faced a chronic disease. CONCLUSIONS: Overall, the diagnostic
      workup seemed to benefit patients and improve their sense of well-being. However,
      whether the effects were beneficial or not depended on the results of the
      diagnostic workup itself. In clinical practice the decision to undergo testing in
      situations in which definitive treatment is unavailable should be individualized.
      The potential for negative as well as positive consequences should be recognized.

PMID- 8274113
TI  - Tuberous sclerosis in Western Sweden. A population study of cases with early
      childhood onset.
AB  - OBJECTIVE: To study the prevalence of tuberous sclerosis in children and
      adolescents. DESIGN: Previously published diagnostic criteria for tuberous
      sclerosis were used. All physicians likely to encounter young patients with
      tuberous sclerosis were contacted by way of a screening questionnaire. SETTING:
      The study was performed in a circumscribed geographic area (western Sweden).
      PATIENTS AND OTHER PARTICIPANTS: The sample was population based. However, only
      patients with such severe and early symptoms that referral to a physician had
      been considered necessary and relatives of these patients with tuberous sclerosis
      could be included. This was because there is currently no diagnostic marker for
      tuberous sclerosis that could be used as a screening tool. RESULTS: The peak
      prevalence (one in 6800 individuals) for tuberous sclerosis was found in the 11-
      to 15-year-old age group. For the whole age cohort, 0 to 20 years, the prevalence
      was one in 12,900 individuals. CONCLUSIONS: The prevalence for the school-age
      group was the highest ever reported in the literature on tuberous sclerosis.
      However, it is likely that the true prevalence of tuberous sclerosis in the
      general population is even higher.

PMID- 8274114
TI  - The importance of Spratling.
AB  - William P. Spratling made important contributions to American epileptology at the
      beginning of this century. He was the first medical superintendent of Craig
      Colony for Epileptics from 1893 to 1908, cofounder and president of the National
      Association for the Study of Epilepsy, and first editor of its scholarly journal,
      Transactions. During his tenure at Craig Colony, Spratling established standards
      for safe and humane public care of epileptics. He started the first American
      residency training program emphasizing epileptology. Spratling conducted the
      first American multicenter research on the causes of death in epilepsy. The
      dosage of bromide therapy, which he empirically determined, remains correct. In
      his book Epilepsy and Its Treatment, Spratling substantiated the cortical origin
      theory of epilepsy developed by Jackson and Gowers. He was the first American to
      postulate and investigate a biochemical etiology of generalized seizures in the
      absence of anatomic lesions. Despite signal accomplishments, his untimely, tragic
      death may explain why he remains obscure.

PMID- 8274115
TI  - One-and-a-half syndrome, type II.
AB  - OBJECTIVE: To describe a second type of the one-and-a-half syndrome in which
      adduction rather than abduction of one eye is the preserved horizontal movement.
      DESIGN AND PATIENT SETTING: A patient experiencing mucormycosis of the cavernous
      sinus suffered a sixth-nerve palsy and simultaneous carotid artery occlusion with
      infarction and a contralateral horizontal gaze palsy. RESULTS: The patient
      experienced an eye movement syndrome with complete paralysis of horizontal eye
      movement in the ipsilateral eye and paralysis of horizontal eye movement in one
      direction, in this case abduction due to the gaze palsy, in the contralateral
      eye. Adduction of the contralateral eye was the only remaining horizontal eye
      movement. CONCLUSION: A lesion in the cavernous sinus producing occlusion of the
      internal carotid artery and a sixth-nerve palsy may produce a second type of one
      and-a-half syndrome. Adduction rather than abduction of one eye is the preserved
      horizontal eye movement. This combination of eye movement deficits is unlikely to
      be produced by a lesion in any other location. Mucormycosis, with its propensity
      to produce vascular occlusion, is a likely, although not specific, cause.

PMID- 8274116
TI  - Dementia of adult polyglucosan body disease. Evidence of cortical and subcortical
      dysfunction.
AB  - OBJECTIVES: To characterize the dementia associated with adult polyglucosan body
      disease (APBD) and to correlate the cognitive deficits with abnormalities found
      on magnetic resonance imaging (MRI). METHODS: Quantitative neuropsychological
      testing and MRI in one man with APBD and a review of the literature. RESULTS: The
      dementia of APBD affects cortical and subcortical functions. The cognitive
      deficits correlate with MRI findings of cortical atrophy and white-matter
      abnormalities. CONCLUSION: Neuropsychological testing and MRI are helpful in the
      evaluation of patients with APBD.

PMID- 8274117
TI  - A longitudinal examination of crossed aphasia.
AB  - OBJECTIVE: To longitudinally examine neuropsychological performance in an adult
      dextral man with crossed aphasia after cerebrovascular accident. DESIGN: Case
      report using longitudinal neuropsychological, neurological, and radiological
      examinations performed in close temporal proximity to one another. SETTING: The
      patient was seen on both an inpatient and an outpatient basis by members of the
      Department of Neurology and Radiology of the University of Miami (Fla) School of
      Medicine. PATIENT: Thirty-four-year-old right-handed monolingual Hispanic man
      without family history of left-handedness. RESULTS: Initial neuropsychological
      testing revealed classic Broca's dysphasia, visual neglect, and visuospatial
      disturbances. The visuospatial disturbance resolved within 6 months whereas
      expressive language remained severely impaired. There was a dissociation between
      praxis and language. Mood was jovial with indifference toward his neurologic and
      cognitive limitations. Serial magnetic resonance imaging studies unequivocally
      localized the lesions to the right hemisphere, involving the right frontal,
      anterior parietal, and subcortical white matter. CONCLUSIONS: The clinicoanatomic
      correlation is compatible with the view that crossed aphasia is a "mirror"
      representation of that seen in cases of uncrossed aphasia. The course of recovery
      suggests complete lateralization of language to the right hemisphere with
      bilateral or crossed representation of nonverbal skills.

PMID- 8274118
TI  - The relationship between regional blood flow and absorption of lignocaine.
AB  - With the increasing application of certain surgical procedures to 'day surgery'
      cases, there has been greater utilization of local anaesthetic agents. Such
      procedures are undertaken using single infiltration dosage recommendations for
      lignocaine, both with and without adrenaline. The present paper describes results
      obtained from a sheep model that considers the role of the regional blood flow of
      the injected site as a determinant of lignocaine absorption and resultant
      pharmacokinetics. The peak concentration of lignocaine in plasma following
      administration to two selected sites of different vascularity (as determined by a
      technetium99 washout method), as well as the effect of concomitant adrenaline
      administration, was shown to correlate with the regional blood flow to the site
      (rs = 0.73, P = 0.008). Extrapolating these animal data to the clinical situation
      suggests that larger dosages of lignocaine could be used safely for infiltration
      anaesthesia in regions of poor regional blood flow without posing a threat of
      lignocaine-induced toxicity, and that the current dosage recommendations could be
      modified in respect of the regional blood flow of the particular site to be
      infiltrated.

PMID- 8274119
TI  - Ten year review of thoracic and abdominal penetrating trauma management.
AB  - A ten year review of penetrating thoracic and abdominal trauma examined pattern
      of injury, patient management and outcome. Ninety-six patients were included in
      the study, 55 with injury to the abdomen, 31 the thorax and 10 with injury to
      both areas. Fifty-eight cases were managed non-operatively; 5 combined abdominal
      and thoracic injuries, 26 thoracic and 27 abdominal. Two cases went on to require
      operative management for intra-abdominal injury. Thirty-eight cases were managed
      operatively; 5 combined cavity injuries, 5 thoracic and 28 abdominal. Injuries
      were found in all of the combined cavity and thoracic cavity cases. Of the 28
      abdominal cases, nine were found on laparotomy to have no significant visceral or
      vessel injury, one, however, was performed for omentum protruding through the
      wound. While a negative laparotomy was a relatively safe procedure, non-operative
      management had the advantages of a shorter hospital stay without wound-related
      morbidity. Selective non-operative management was found to be a relatively safe
      approach in this series.

PMID- 8274120
TI  - Delayed traumatic extradural haematomas.
AB  - A total of 76 patients with traumatic extradural haematoma were treated within a
      period of 3 years. Four patients developed delayed extradural haematomas. These
      cases are reported in view of the unusual sequence and the importance of early
      diagnosis.

PMID- 8274121
TI  - Sports-related facial fractures: a review of 137 patients.
AB  - One hundred and thirty-seven patients with sports-related facial fractures were
      reviewed. These made up 16.3% of 839 patients with facial fractures seen at the
      Department of Plastic and Reconstructive Surgery, Royal Adelaide Hospital,
      between June 1989 and June 1992. Males made up 93.4% of patients and 89.1% were
      aged below 35 years. There was an intent to injure in 11%. Australian Rules
      football was the causative sport in 52.6%, all the injuries being the result of
      human contact. Orbitozygomatic fractures were the most frequently observed
      overall (62%) as well as in Australian Football (58.3%). Cricket contributed to
      14.6%, the ball being the agent of injury in all but one of the patients. Horse
      riding injuries were the most severe. 89.1% of the patients required surgery and
      hospital stays ranged from 0 to 18 days with an average stay of 4.7 days. Sports
      activities, although a significant source of enjoyment, are a significant cause
      of facial fractures with their attendant morbidity.

PMID- 8274122
TI  - Helicopter retrieval of primary trauma patients by a paramedic helicopter
      service.
AB  - All trauma cases flown over a 3.5 year period by the Metropolitan Helicopter
      Ambulance (MHA) from the accident scene to the Alfred Hospital were analysed. The
      MHA carries paramedics trained in advanced life support and is not under direct
      medical control. There were 254 patients (226 males, 28 females, mean age 34
      years) of whom 242 had sustained blunt trauma. The mean distance from the
      accident scene to hospital was 28 nautical miles. The mean time from dispatch of
      the MHA to arrival at the Alfred was 82 min. The mean ground time at the scene
      was 32 min. Major trauma (an injury severity score (ISS) of 15 or more) was
      present in 62% of patients, and the mean ISS was 22.4. The major treatments at
      the accident scene by the paramedics were insertion of an intravenous (i.v.)
      cannula (242 cases), application of splints (197 cases), endotracheal intubation
      (35 patients) and needle thoracostomy to exclude tension pneumothorax (18 cases).
      There were 25 patients with a Glasgow Coma Score (GCS) less than 8 who were not
      intubated at the scene. Review of paramedic management identified four cases
      where prehospital care could have been improved but it is unlikely the final
      outcome would have changed: delay in transport (1 case), inadequate i.v. fluid
      resuscitation (2 cases) and delay in intubation (1 case). There was 1 case of
      undiagnosed tension pneumothorax that contributed to the patient's death and 1
      case of non-intubation where the outcome may have been altered. Overall there
      were 38 deaths (14% mortality), which was not significantly different from the
      predicted mortality of 17%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274123
TI  - Plastic adhesive drapes and wound infection after hip fracture surgery.
AB  - One hundred and twenty patients with acute hip fractures treated operatively were
      randomized into two groups. In the 'drape' group (n = 65) the operation site was
      covered with plastic adhesive drape after preparation. In the 'no drape' group (n
      = 55) the operation site was left uncovered. The two groups were otherwise
      matched. Swabs for culture were taken from skin adjacent to the wound before
      closure. The drape group had four positive wound swabs. There was only one
      positive wound swab for the no-drape group. There was no difference in the post
      operative wound infection rates.

PMID- 8274124
TI  - Mirizzi's syndrome: identification and management strategy.
AB  - Fourteen cases of Mirizzi's syndrome are presented here. Clinical presentation
      was pain (14), jaundice (14), fever (10) and peritonitis (1). A clinical
      diagnosis of choledocholithiasis was considered in all the patients. Pre
      operative diagnosis of Mirizzi's syndrome was made in five patients on the basis
      of cholangiogram and the remaining cases were diagnosed at surgery. The stage
      (type) of Mirizzi's syndrome was based on the extent of erosion of the common
      bile duct. Four patients had type I, seven type II and three type III lesions.
      Associated choledocholithiasis was present in five and acute free perforation of
      the gall-bladder in one. The operative procedures performed were partial
      cholecystectomy for type I, partial cholecystectomy, choledochoplasty and T-tube
      choledochostomy for type II and bilioenteric anastomosis for type III lesions.
      Two patients had retained common bile duct stones. Mean follow up was 14 months
      (range 1-27 months). One patient with secondary biliary cirrhosis continues to
      have persistently elevated serum alkaline phosphatase levels without any
      demonstrable biliary obstruction. Diagnostic and operative strategies are
      discussed and a follow up protocol for such patients is suggested.

PMID- 8274125
TI  - Tuberculosis of the thyroid gland: a clinicopathological profile of four cases
      and review of the literature.
AB  - Four cases of tuberculosis of the thyroid with different presentations including
      chronic sinus (following drainage of thyroid abscess), thyrotoxicosis, severe
      dysphagia clinically mimicking malignancy and euthyroid multinodular goitre are
      described. Except in the case presenting with chronic sinus (discharging acid
      fast bacilli), the diagnosis was a pathological surprise (cytopathology in one
      and histopathology in two). Only in one case was there evidence of disease
      outside the cervical region. All cases showed multiple coalescing and caseating
      epitheloid cell granulomas along with giant cells, which are considered as
      diagnostic of tuberculous thyroiditis even if acid fast bacilli cannot be
      demonstrated. The literature is reviewed and the pathogenesis discussed.

PMID- 8274126
TI  - Obturator foramen bypass in the management of infected prosthetic vascular
      grafts.
AB  - The obturator foramen bypass graft remains an excellent option for
      revascularizing the lower extremity when dealing with an infected prosthetic
      vascular graft in the groin. In this series, six obturator foramen bypass grafts
      were performed in five patients for infectious groin complications following
      vascular surgery. Conservative measures such as local antibiotic irrigation and
      abscess drainage designed to preserve the graft in situ had failed to eradicate
      the infection in all instances and was complicated by suture-line haemorrhage in
      three instances. An aggressive approach should be adopted, aimed at excision of
      the infected graft. The obturator foramen bypass graft remains a durable graft
      for limb salvage. Five out of six obturator foramen bypass grafts were patent
      after 11-26 months follow up.

PMID- 8274127
TI  - The evolution and development of the urinary catheter.
AB  - The urinary catheter is one of the most frequently used medical devices and has a
      long and intriguing history of development. This paper describes the catheter
      from its simple beginnings through the subtle but important changes it has
      undergone paralleling the advances in plastics technology witnessed this century.
      The changes have not been without controversy and the recent association of
      catheters with tissue toxicity, which has forced the implementation of strict
      guidelines for their manufacture and use, is described.

PMID- 8274128
TI  - Malignant melanoma of the penis.

PMID- 8274129
TI  - Torsion of the fundus of the gall-bladder.
AB  - A rarely described form of gall-bladder torsion is presented where only the
      distal fundus underwent torsion and subsequently infarcted. This case highlights
      the need to be aware of the diagnosis in order to enable early surgical
      intervention to be undertaken and thus avoid morbidity.

PMID- 8274130
TI  - Ilioinguinal nerve entrapment from laparoscopic hernia repair.

PMID- 8274131
TI  - Primary torsion of the greater omentum.

PMID- 8274132
TI  - Perforation of the stomach by fish bone producing delayed transient obstructive
      jaundice.

PMID- 8274133
TI  - Central acetabular fracture with ipsilateral displaced fracture of the femoral
      neck.

PMID- 8274134
TI  - Effects of the residue adjacent to the reactive serine on the substrate
      interactions of Drosophila esterase 6.
AB  - Esterase 6 from Drosophila melanogaster is a carboxylesterase that belongs to the
      serine esterase multigene family. It has a basic histidine (His) at residue 187,
      adjacent to the reactive serine (Ser) at residue 188, whereas most other
      characterized members of the family have an acidic glutamate (Glu) in the
      equivalent position. We have used site-directed in vitro mutagenesis to replace
      the His codon of the esterase 6 gene with either Gln or Glu codons. The enzymes
      encoded by these active-site mutants and a wild-type control have been expressed,
      purified, and characterized. Substitution of Gln for His at position 187 has
      little effect on the biochemical properties of esterase 6, but the presence of
      Glu at this position is associated with three major differences. First, the pH
      optimum is increased from 7 to 9. Second, the mutant enzyme shows decreased
      activity for beta-naphthyl esters and p-nitrophenyl acetate but has gained the
      ability to hydrolyze acetylthiocholine. Finally, the Gibb's free energy of
      activation for the enzyme is increased. These results suggest that residue 187
      interacts directly with the substrate alkyl group and that this interaction is
      fully realized in the transition state. We further propose that the presence of
      His rather than Glu at position 187 in esterase 6 contributes significantly to
      its functional divergence from the cholinesterases and that this divergence is
      due to different interactions between residue 187 and the substrate alkyl group.

PMID- 8274135
TI  - Esterase-30 (ES-30) of the house mouse: biochemical characterization and genetics
      of a new carboxylesterase isozyme linked to cluster-2 loci on chromosome 8.
AB  - A new carboxylesterase isozyme (EC 3.1.1.1), designated ES-30, is described in
      mouse liver. Two phenotypes were distinguished, ES-30A, a possible null type, was
      found in SPE/Pas and in other lines derived from Mus spretus, and ES-30B was
      found in BALB/cJ and other laboratory inbred strains. ES-30B is characterized by
      a distinct electrophoretic band when stained using 5-bromoindoxyl acetate as the
      substrate. After isolation and purification from other esterases by ion-exchange
      chromatography and molecular sieving, the molecular mass was estimated by two
      independent methods to be 62 and 64 kDa, respectively. The activity of ES-30B is
      higher in adult males than in females and can be stimulated in vivo by
      testosterone. The distribution of phenotypes on the progeny of a backcross series
      suggests a separate locus, Es-30, with the allele a for absence and b for
      presence of the isozyme. Locus Es-30 is shown to be closely linked to Es-2 and to
      Es-7 of cluster-2 on chromosome 8. The gene order Es-9--Got-2--(Es-2, Es-7, Es
      30) is suggested.

PMID- 8274136
TI  - Latitudinal allozymic variability in natural populations of Zaprionus indianus
      from India.
AB  - Twelve natural populations of Z. indianus from India, collected along lines of
      latitude, were analyzed electrophoretically and the geographical pattern of
      variation was compared at 15 allozyme loci. Except for Mdh-2, all the loci
      revealed extensive polymorphism. The allele frequency variation revealed a
      statistically significant correlation as well as regression coefficients with the
      latitude. The populations revealed extensive clinical variation at all the
      polymorphic loci, which depicted moderate to higher FST values. Thus, the
      observed genetic divergence in colonizing populations of Z. indianus shows the
      role of natural selection that varies spatially along the north-south axis of the
      Indian subcontinent.

PMID- 8274137
TI  - The amino acid sequence of the alpha subunit of mouse salivary androgen-binding
      protein (ABP), with a comparison to the partial sequence of the beta subunit and
      to other ligand-binding proteins.
AB  - It has been suggested that three distinct genes, Abpa, Abpb, and Abpg, determine
      the three subunits of mouse salivary androgen-binding protein (ABP) (Dlouhy, S.
      R., et al., Genetics 115, 535, 1987). We report the putative amino acid sequence
      of the subunit common to all forms of ABP, the Alpha subunit, and the partial
      amino acid sequence of the Beta subunit. These sequences have little in common,
      supporting the notion of at least two distinct genes coding for the subunits of
      the most common form of salivary ABP, the A:B dimer. A search of GenBank showed
      that these sequences have not been reported previously. The Beta subunit shows
      significant homology with helospectin, a member of the glucagon superfamily, but
      not enough homology to assign it to the family. No homology exists between ABP
      subunits and members of the ligand-binding carrier family of proteins nor does
      ABP show homology with other androgen-binding proteins. Particularly interesting
      is the observation that there is no relationship to rat prostatic steroid binding
      protein (PBP), given the similarities in protein tertiary structure, the numbers
      of subunits and their genes, and the earlier observation of ABP cross-reactive
      material in mouse prostate.

PMID- 8274138
TI  - DNA isolation by a rapid method from human blood samples: effects of MgCl2, EDTA,
      storage time, and temperature on DNA yield and quality.
AB  - The isolation of DNA from whole blood by a modified rapid method (RM) was tested
      using various detergents and buffer conditions. Extraction of DNA with either NP
      40 or Triton X-100 gave a high yield of undegraded DNA in less than an hour. The
      concentration of magnesium ion in the buffers was critical to obtaining intact,
      high molecular weight (HMW) DNA. Greater than 10 mM MgCl2 led to degradation.
      Addition of EDTA to the buffer inhibits this degradation. Preparation of DNA from
      blood stored at room temperature or incubated at 37 degrees C for 24 hr resulted
      in the same amount and quality of DNA as from samples frozen at -70 degrees C.
      DNA from blood samples that had undergone more than four freeze-thaw cycles was
      found to be partially degraded. The modified RM can be applied to extract DNA
      from as little as 10 microliters of blood (340 ng of DNA) and from dried blood
      samples. DNA samples remained intact and undegraded for longer times when DNA was
      dissolved in higher concentrations of EDTA.

PMID- 8274139
TI  - A Drosophila homologue of the Schizosaccharomyces pombe act2 gene.
AB  - Diverse proteins that are 35% to 55% identical to actins have been discovered
      recently in yeasts, nematodes, and vertebrates. In order to study these proteins
      systematically and relate their functions to those of conventional actins, we are
      isolating the corresponding genes from the genetically tractable eukaryote,
      Drosophila melanogaster. Here we report the isolation and partial
      characterization of a Drosophila homologue of the Schizosaccharomyces pombe act2
      gene. Degenerate oligonucleotide primers specifying peptides that are highly
      conserved within the actin protein superfamily were used in conjunction with
      polymerase chain reaction (PCR) to amplify a portion of the Drosophila gene that
      we have named actr66B. The corresponding full-length cDNA sequence encodes a
      protein of 418 residues that is 65% identical to the product of the S. pombe act2
      gene, 80% identical to the bovine act2 homologue, but only 48% identical to the
      principal Drosophila cytoplasmic actin encoded by the Act5C actin gene. Alignment
      of the yeast, bovine, and Drosophila actin-related proteins shows that they have
      four peptide insertions, relative to conventional actins, three of which are well
      placed to modify actin polymerization and one that is likely to perturb the
      binding of myosin. Locations of two of the five actr66B introns are conserved
      between Drosophila and yeast genes, further attesting that they evolved from a
      common ancestor and are likely to encode proteins having similar functions. We
      demonstrate that the Drosophila gene is located on the left arm of chromosome 3,
      within subdivision 66B. Finally, we show by RNA blot-hybridization that the gene
      is expressed at low levels, relative to conventional nonmuscle actin, in all
      developmental stages. From these and other observations we infer that the actr66B
      protein is a minor component of all cells, perhaps serving to modify the
      polymerization, structure, and dynamic behavior of actin filaments.

PMID- 8274140
TI  - Gamma-tubulin: the hub of cellular microtubule assemblies.
AB  - In eukaryotic cells a specialized organelle called the microtubule organizing
      center (MTOC) is responsible for disposition of microtubules in a radial,
      polarized array in interphase cells and in the spindle in mitotic cells.
      Eukaryotic cells across different species, and different cell types within single
      species, have morphologically diverse MTOCs, but these share a common function of
      organizing microtubule arrays. MTOCs effect microtubule organization by
      initiating microtubule assembly and anchoring microtubules by their slowly
      growing minus ends, thus ensuring that the rapidly growing plus ends extend
      distally in each microtubule array. The goal is to define molecular components of
      the MTOC responsible for regulating microtubule assembly. One approach to
      defining the molecules responsible for MTOC function is to look for molecules
      common to all MTOCs. A newly discovered centrosomal protein, gamma-tubulin, is
      found in MTOCs in cells from many different organisms, and has several properties
      which make it a candidate for both initiation of microtubule assembly and
      anchorage. The hypothesis that gamma-tubulin plays a role in MTOCs in microtubule
      initiation and anchorage is currently being tested by a variety of experimental
      approaches.

PMID- 8274141
TI  - Common mechanisms for the control of eukaryotic transcriptional elongation.
AB  - Regulation of transcriptional elongation is emerging as an important control
      mechanism for eukaryotic gene expression. In this essay, we review the basis of
      the current view of the regulation of elongation in the human c-myc gene and
      discuss similarities in elongation control among the c-myc, Drosophila hsp70 and
      the HIV-1 genes. Based upon these similarities, we propose a model for control of
      expression of these genes at the elongation phase of transcription. This model
      suggests that distinct promoter elements direct the assembly of RNA polymerase II
      transcription complexes which differ in their elongation efficiency.

PMID- 8274142
TI  - Protein splicing: excision of intervening sequences at the protein level.
AB  - Protein splicing is an extraordinary post-translational reaction that removes an
      intact central "spacer" domain (Sp) from precursor proteins (N-Sp-C) while
      splicing together the N- and C-domains of the precursor, via a peptide bond, to
      produce a new protein (N-C). All of the available data on protein splicing fit a
      model in which these intervening sequences excise at the protein level via a self
      splicing mechanism. Several proteins have recently been discovered that undergo
      protein splicing, and in two such cases, the excised spacer protein is an
      endonuclease. Such endonucleases are capable of conferring genetic mobility upon
      the intervening sequences that encodes them. These intervening sequences define a
      new family of mobile genetic elements that are translated yet remain
      phenotypically silent by excising at the protein rather than the RNA level.

PMID- 8274143
TI  - The aminoacyl-tRNA synthetase family: modules at work.
AB  - The combined use of molecular and structural biology techniques has proved very
      efficient in elucidating structure-function relationships in aminoacyl-tRNA
      synthetases. Our present understanding of this family of enzymes is based on two
      main unifying principles: (i) division into two different classes, corresponding
      to two different modes of ATP binding and attachment of the activated amino acid
      to the last nucleotide of tRNA (either 2'OH or 3'OH of the ribose) by two
      different catalytic mechanisms and two structural domains with completely
      different folding, and (ii) the modular organization into separate and additional
      domains that we are just beginning to understand. Sequence analysis complements
      very nicely existing structural, biochemical and genetic results and makes them
      more general, leading to verifiable predictions.

PMID- 8274144
TI  - Lipoprotein oxidation and gene expression in the artery wall. New opportunities
      for pharmacologic intervention in atherosclerosis.

PMID- 8274145
TI  - Glutathione transferase isoenzymes in olfactory and respiratory epithelium of
      cattle.
AB  - Glutathione transferase (GST) was investigated in the olfactory and respiratory
      epithelium of cattle. A significantly more abundant GST in terms of either
      protein amount or activity was found in the olfactory rather than in the
      respiratory epithelium. No apparent qualitative differences in the isoelectric
      focusing, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE)
      and HPLC profiles were noted in the reduced glutathione (GSH) affinity purified
      GST pool of olfactory and respiratory epithelium. Both tissues have at least six
      GST isoenzymes with isoelectric point values of 4.9 (peak I), 5.3 (peak II), 5.95
      (peak III), 6.5 (peak IV), 7.1 (peak V) and 9.3 (peak VI). From both tissues at
      least seven different GST subunits can be resolved by HPLC analysis. The GST
      isoenzymes having pI at 5.3 and 9.3 were predominantly expressed in the olfactory
      than in the respiratory epithelium. These latter forms conjugate GSH efficiently
      with alkenals and hydroperoxides, respectively. Kinetic, immunological and
      structural properties, including HPLC analysis and N-terminal region amino acid
      sequence seem to indicate that the bovine nasal mucosa tissue in addition to a
      GST subunit which is orthologue to rat subunit 8 (alpha class) express tissues
      specific subunits.

PMID- 8274146
TI  - Inhibition of aldehyde dehydrogenases by methylene blue.
AB  - The effect of the redox dye methylene blue on the stability of NADH and on the
      activity of the enzyme aldehyde dehydrogenase (ALDH; EC 1.2.1.3) was examined.
      NADH was measured by HPLC with fluorometric or spectrophotometric detection. The
      ALDH activity assays were carried out by following the formation of 3,4
      dihydroxyphenylacetic acid (DOPAC) from 3,4-dihydroxyphenylacetaldehyde (DOPAL)
      using HPLC and electrochemical detection. Incubation of NADH solutions in the
      presence of methylene blue resulted in a time-dependent direct oxidation of NADH.
      Methylene blue inhibited the human erythrocyte and leukocyte ALDHs and the rat
      liver mitochondrial low-Km ALDH in a concentration-dependent manner. The
      inactivation was reversible by dilution, and kinetic analysis indicated that
      methylene blue inhibits the rat liver mitochondrial low-Km and human erythrocyte
      ALDHs competitively with respect to DOPAL, while no effect of the NAD+
      concentration was apparent. For the rat liver low-Km ALDH, a Ki of 8.4 +/- 2.8
      microM (mean +/- SD; N = 5) was calculated. The inhibition of ALDH and the
      resulting decrease in the redox effect on the NAD system bound to alcohol
      dehydrogenase (EC 1.1.1.1) could explain the protective effect of methylene blue
      against metabolic redox effects of ethanol.

PMID- 8274147
TI  - Inhibition of poly(ADP-ribose) polymerization preserves the glutathione pool and
      reverses cytotoxicity in hydrogen peroxide-treated lymphocytes.
AB  - DNA damage caused by oxygen radicals activates poly(ADP-ribosyl) polymerase
      (pADPRP), a nuclear enzyme that utilizes NAD+ as substrate. It has been
      demonstrated that pharmacological inactivation of pADPRP rescues human
      lymphocytes damaged by oxygen radicals, but not those damaged by equitoxic doses
      of ionizing radiation. In the present paper we demonstrate that the NAD+ pool
      decreases after both damaging treatments and is preserved in a similar fashion by
      pADPRP inhibition. On the contrary, the ATP pool, cell energy charge and reduced
      thiols are decreased only by the administration of oxygen radicals, and are
      preserved if poly(ADP)ribosylation is inhibited. In fact, treatment with oxidant
      agents depletes the cell energy pools owing to the simultaneous demands of the
      glutathione (GSH)/NADPH cycle and pADPRP-driven NAD+ consumption, while in
      irradiated cells only the latter mechanism operates. We suggest that, when pADPRP
      is inhibited, enough energy is available for the preservation of cell thiols,
      thereby allowing oxidant-treated cells to survive and undergo mitosis. Thus, GSH
      and energy shortage appear to be the main cause of cell death in oxidant-injured
      cells.

PMID- 8274148
TI  - C-terminal modifications of pertussis toxin-sensitive G-protein alpha-subunits
      differentially affect immunoreactivity. Evidence against endogenous ADP
      ribosylation in human heart, lung, thrombocytes and adipose tissue.
AB  - Immunochemical detection of pertussis toxin-sensitive guanine-nucleotide binding
      proteins has been suggested to represent the most direct approach to quantitate
      the protein than pertussis toxin-catalysed [32P]ADP-ribosylation. The latter
      technique is potentially hampered by pre-existing covalent modification of the C
      terminus. However, limited data exist as to whether and in what way modifications
      of the C-terminus affect immunoreactivity of Gi alpha (alpha-subunit of the
      inhibitory G-protein of adenylyl cyclase). Membranes from human myocardium,
      thrombocytes, adipose tissue and lung were treated with pertussis toxin or N
      ethylmaleimide. Both, conditions prevented high affinity agonist binding to m
      cholinoceptors and inhibited [32P]ADP-ribosylation by pertussis toxin consistent
      with the notion that the modifications took place at the C-terminus. Pertussis
      toxin treatment increased immunoreactivity to different antisera raised against
      the C-terminal decapeptide of transducin alpha (KENLKDCGLF, DS 1-4, AS). N
      Ethylmaleimide reduced immunoreactivity towards all antisera studied. Pertussis
      toxin reduced the mobility of Gi alpha on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis (SDS-PAGE) depending on the presence of the toxin and
      sensitivity to inhibition of ADP-ribosylation by nicotinamide. In native
      membranes from none of the tissues studied, immunoreactive material comigrating
      with pertussis toxin-modified form of Gi alpha was detected. It is concluded that
      modification of the C-terminus by pertussis toxin or N-ethylmaleimide resulting
      in the same functional consequence, i.e. prevention of high affinity agonist
      receptor binding, is capable of producing opposite changes of immunoreactivity.
      Pertussis toxin treatment reduces the electrophoretic mobility on SDS-PAGE.
      Separation of the native and pertussis toxin-modified form of Gi alpha on SDS
      PAGE demonstrates that endogenously ADP-ribosylated Gi alpha is lacking in
      membranes from human myocardium, thrombocytes, lung and adipose tissue.

PMID- 8274149
TI  - Comparative cytotoxicity of angiotensin-converting enzyme inhibitors in cultured
      rat hepatocytes.
AB  - Captopril and enalapril, angiotensin-converting enzyme inhibitors (ACEIs), have
      been associated with idiosyncratic hepatotoxicity. Such drug reactions may be
      caused by the formation of reactive metabolites by cytochrome P450 isozymes,
      which can then cause direct or immune-mediated toxicity. Previously, we have
      demonstrated that enalapril cytotoxicity in primary cultures of rat hepatocytes
      was due, at least in part, to cytochrome P450-dependent metabolism, and that
      glutathione was involved in the detoxification process. In the present study, we
      extended our investigations into mechanisms of cytotoxicity, using rat hepatocyte
      cultures, to captopril and three recently marketed ACEIs: fosinopril, lisinopril
      and quinapril. After 24 hr of exposure to lisinopril or enalaprilat (the
      deesterified metabolite of enalapril), hepatocytes did not show any evidence of
      cytotoxicity, measured by lactate dehydrogenase leakage, even at 10 mM drug
      concentrations. The other ACEIs were toxic to the liver cells, with the rank
      order of toxicity as quinapril (LC50 = 0.28 mM) > fosinopril (LC50 = 0.4 mM) >
      enalapril (LC50 = 2.0 mM) > captopril (LC50 = 20 mM). In vivo pretreatment of
      rats with pregnenolone-16 alpha-carbonitrile to induce isozymes of the P450 3A
      subfamily significantly enhanced the cytotoxicities of quinapril, fosinopril and
      enalapril but did not affect captopril cytotoxicity. Pretreatment with P450
      inducers selective for other isozyme subfamilies (ethanol, beta-naphthoflavone
      and phenobarbital) did not alter the in vitro toxicity of any of the ACEIs. Co
      incubation with SKF525-A (15 microM) or troleandomycin (0.1 mM) reduced the
      hepatocidal toxicities of quinapril, fosinopril and enalapril. Preincubation with
      buthionine sulfoximine (2 mM) enhanced the cytotoxicities of quinapril,
      fosinopril, enalapril and captopril. The results of this study indicate that like
      enalapril, quinapril and fosinopril can also undergo P450 3A-dependent
      bioactivation and require maintenance of glutathione status for detoxification,
      and that captopril causes cytotoxicity independent of cytochrome P450 metabolism.

PMID- 8274150
TI  - Cimetidine-induced seizures in mice. Antagonism by some GABAergic agents.
AB  - The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid
      (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone
      and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine
      (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA
      and DABA effectively protected mice against cimetidine-induced seizures.
      Bicuculline and picrotoxin significantly potentiated the seizures induced by
      cimetidine and effectively antagonized the protective effects of muscimol, AOAA
      and DABA against the seizures. Diazepam and phenobarbitone significantly
      protected the mice against cimetidine-induced seizures while phenytoin and
      strychnine did not significantly alter the seizures. These results indicate that
      the attenuation of central gamma-aminobutyric acid neurotransmission may underlie
      cimetidine-induced seizures in mice.

PMID- 8274152
TI  - Regulation of renal cytochrome P450s by thyroid hormone in diabetic rats.
AB  - Effects of thyroid hormone treatment on renal P450 expression in the diabetic
      rats were investigated. Diabetes produced by streptozotocin induced CYP4A2 and
      P450 K-2 (similar form with CYP2C23) but not P450 K-4 (similar form with CYP4A8)
      and induced lauric acid hydroxylation activity. The serum thyroid hormone level
      was decreased with diabetes. Treatment of diabetic rats with thyroid hormone (T3)
      as well as with insulin reversed the increase in the levels of CYP4A2 and P450 K
      2. Thyroidectomy also induced CYP4A2 and P450 K-2 in the rat kidney. The increase
      was reversed by treatment of thyroidectomized rats with T3. These findings
      suggest that expression of CYP4A2 and P450 K-2 in rat kidney is suppressively
      regulated by thyroid hormone and the decrease in thyroid hormone level in the
      diabetic state affects the levels of CYP4A2 and P450 K-2.

PMID- 8274151
TI  - Structural and metabolic requirements for activators of the peroxisome
      proliferator-activated receptor.
AB  - Fatty acids have recently been demonstrated to activate peroxisome proliferator
      activated receptors (PPARs) but specific structural requirements of fatty acids
      to produce this response have not yet been determined. Importantly, it has
      hitherto not been possible to show specific binding of these compounds to PPAR.
      To test whether a common PPAR binding metabolite might be formed, we tested the
      effects of long-chain omega-3 polyunsaturated fatty acids, differentially beta
      oxidizable fatty acids and inhibitors of fatty acid metabolism. We determined the
      activation of a reporter gene by a chimaeric receptor encompassing the DNA
      binding domain of the glucocorticoid receptor and the ligand binding domain of
      PPAR. The omega-3 unsaturated fatty acids were slightly more potent PPAR
      activators in vitro than saturated fatty acids. The peroxisomal proliferation
      inducing, non-beta-oxidizable, tetradecylthioacetic acid activated PPAR to the
      same extent as the strong peroxisomal proliferator WY 14,643, whereas the
      homologous beta-oxidizable tetradecylthiopropionic acid was only as potent as a
      non-substituted fatty acid. Cyclooxygenase inhibitors, radical scavengers or
      cytochrome P450 inhibitors did not affect activation of PPAR. In conclusion, beta
      oxidation is apparently not required for the formation of the PPAR-activating
      molecule and this moiety might be a fatty acid, its ester with CoA, or a further
      derivative of the activated fatty acid prior to beta-oxidation of the acyl-CoA
      ester. These data should aid understanding of signal transduction via PPAR and
      the identification of a receptor ligand.

PMID- 8274153
TI  - Metabolism of 5'-ether prodrugs of 1-beta-D-arabinofuranosyl-E-5-(2
      bromovinyl)uracil in rats.
AB  - 1-beta-D-Arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU) is a selective
      antiherpesviral agent that has been shown to be metabolically stable in mice.
      However, E-5-(2-bromovinyl)uracil (BVU) is the major metabolite found after oral
      dosing in animals other than mice. When BV-araU was given orally to germ-free
      rats, only small amounts of BVU were found in the plasma, suggesting an important
      role of enterobacteria in the formation of BVU. Then, the metabolism of BV-araU
      prodrugs was studied in specific-pathogen free rats to select oral prodrugs of BV
      araU with enhanced metabolic stability. 5'-O-Ethyl BV-araU (Et-BV-araU) gave
      about a 2-fold higher BV-araU blood concentration 3 and 6 hr after administration
      than after oral dosing of BV-araU, while the level of BVU was lower. Other
      aliphatic alkyl prodrugs also gave a lower level of BVU, but did not give the
      same elevation in blood concentration of BV-araU as did Et-BV-araU. Dosing of 5'
      O-acetyl BV-araU resulted in blood concentrations of BV-araU and BVU similar to
      those after oral administration of BV-araU. 5'-O-Aromatic alkyl prodrugs showed
      poor bioavailability. A nearly 2-fold higher urinary recovery rate was seen for
      Et-BV-araU than for BV-araU or 5'-O-acetyl BV-araU. The conversion of Et-BV-araU
      to BV-araU was demonstrated in vitro using rat liver extract in the presence of
      co-factors, although the reaction was slow. The 5'-O-aliphatic alkyl prodrugs
      were completely resistant to degradation by enterobacteria, whereas the esters
      were partially degraded to BVU. Et-BV-araU may be a useful oral prodrug of BV
      araU due to its increased metabolic stability and bioavailability.

PMID- 8274154
TI  - Varicella-zoster virus thymidine kinase. Characterization and substrate
      specificity.
AB  - The varicella-zoster virus (VZV) thymidine kinase (TK) EC 2.7.2.21) catalyzes the
      phosphorylation of many anti-VZV nucleosides. Purified, bacterially expressed VZV
      TK was characterized with regard to N-terminal amino acid sequence, pI value, pH
      optimum, metal ion requirement, phosphate donor and acceptor specificity, and
      inhibition by dTTP. Initial velocities of thymidine phosphorylation with variable
      MgATP concentrations fit a two-site model with apparent Km values for MgATP of
      0.10 and 900 microM. dTTP was a noncompetitive inhibitor of thymidine
      phosphorylation but was competitive with MgATP. Phosphate donor and acceptor
      specificities of the bacterially expressed enzyme were indistinguishable from
      those of VZV TK purified from infected cells. Detailed studies of the nucleoside
      specificity with the bacterially expressed enzyme showed that, for a given sugar
      moiety, thymine nucleosides were the most efficient substrates followed by
      nucleosides of cytosine, uracil, adenine, and with some exceptions, guanine. For
      a given pyrimidine or purine (except guanine), 2'-deoxyribonucleosides were the
      most efficient substrates, followed by arabinosides, ribonucleosides, 2',3'
      dideoxyribonucleosides, and the acyclic moiety of acyclovir.

PMID- 8274155
TI  - Calcium as a permissive factor but not an initiation factor in DNA synthesis
      induction in cultured rat hepatocytes by the peroxisome proliferator
      ciprofibrate.
AB  - The non-genotoxic hepatocarcinogen and peroxisome proliferating agent,
      ciprofibrate, is a liver mitogen both in vivo and in cultured adult rat
      hepatocytes, but the mechanisms of its mitogenicity have not been elucidated. We
      previously observed that ciprofibrate rapidly increased hepatocyte free
      intracellular Ca2+ concentration ([Ca2+]i), suggesting that this effect may play
      a role in the initiation of DNA synthesis. In the present study, we have
      identified a relationship between Ca2+ and the stimulation of hepatocyte DNA
      synthesis by ciprofibrate. Exposure of cultured adult rat hepatocytes to
      ciprofibrate (200 microM) for 48 hr increased DNA synthesis by approximately 2
      fold, and this response was attenuated in a Ca(2+)-deficient medium and by the
      Ca2+ channel blockers nicardipine and verapamil. To examine the relationship
      between the stimulation of hepatocyte DNA synthesis and increases in [Ca2+]i by
      ciprofibrate, the intracellular Ca2+ chelator 5,5'-dimethyl-1,2-bis(2
      aminophenoxyethane)-N,N,N',N'-tetraacetic acid (dimethyl-BAPTA) was employed.
      Pretreatment of hepatocytes with dimethyl-BAPTA blocked ciprofibrate-induced
      [Ca2+]i increase, but did not block ciprofibrate-induced hepatocyte DNA
      synthesis. Dimethyl-BAPTA was only effective in reducing ciprofibrate-induced DNA
      synthesis when present during the latter 24 hr of a 48-hr culture period. These
      data suggest that the early mobilization of hepatocyte [Ca2+]i by ciprofibrate
      does not play an initiating role in the induction of hepatocyte DNA synthesis but
      rather may operate as a permissive factor for the entry of ciprofibrate-treated
      adult rat hepatocytes into S-phase.

PMID- 8274156
TI  - The in vivo metabolic stability of dipeptide analogues of the quinazoline
      antifolate, ICI 198583, in mice.
AB  - In the search for quinazoline thymidylate synthase inhibitors that are not
      subject to intracellular polyglutamation, a class of dipeptide analogues of the
      diglutamate of 2-desamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI
      198583-gamma-L-glu) has been evaluated for their stability to in vivo hydrolysis.
      Replacement of the second glutamate with another amino acid, e.g. alanine,
      prevented polyglutamation in vitro but such compounds were subject to hydrolysis
      when injected into mice. The extent of hydrolysis was measured in plasma, liver
      and kidney by HPLC analysis of tissue removed from mice 1 hr after i.p.
      injection. The enzyme responsible for this hydrolysis is thought to be a gamma
      glutamyl hydrolase which hydrolyses the amide bond, releasing ICI 198583 which
      may then be polyglutamated. Development of stable dipeptide compounds was
      achieved by structural modification in two principal ways: either by replacement
      of the second amino acid (e.g. glutamate or alanine) with its D-enantiomer or
      removal of the carboxyl on the alpha-carbon of the second amino acid (alpha'
      COOH). In this second approach two series of compounds were investigated.
      Monocarboxylate-derived dipeptides, e.g. ICI 198583-gamma-L-phenylalanine or ICI
      198583-gamma-phenylglycine, resulted in stable compounds after removal of the
      alpha'-COOH (to give -ethylamide and -benzylamide derivatives, respectively).
      However, for the dicarboxylic amino acids a less clear picture emerged. Although
      removal of the alpha'-COOH from ICI198583-gamma-L-glutamate to give ICI 198583
      gamma-gamma-aminobutyric acid resulted in a stable compound, the corresponding
      aspartate analogue (-beta-alanine) was subject to hydrolysis.

PMID- 8274157
TI  - Urinary porphyrins as biological indicators of oxidative stress in the kidney.
      Interaction of mercury and cephaloridine.
AB  - Reduced porphyrins (hexahydroporphyrins, porphyrinogens) are readily oxidized in
      vitro by free radicals which are known to mediate oxidative stress in tissue
      cells. To determine if increased urinary porphyrin concentrations may reflect
      oxidative stress to the kidney in vivo, we measured the urinary porphyrin content
      of rats treated with mercury as methyl mercury hydroxide (MMH) or cephaloridine,
      both nephrotoxic, oxidative stress-inducing agents. Rats exposed to MMH at 5 ppm
      in the drinking water for 4 weeks showed a 4-fold increase in 24-hr total urinary
      porphyrin content and a 1.3-fold increase in urinary malondialdehyde (MDA), an
      established measure of oxidative stress in vivo. Treatment with cephaloridine
      alone (10-500 mg/kg, i.p.) produced a dose-related increase in urinary MDA and
      total porphyrin levels up to 1.6 and 7 times control values, respectively.
      Injection of MMH-treated rats with cephaloridine (500 mg/kg) caused a synergistic
      (20-fold) increase in urinary porphyrin levels, but an additive (1.9-fold)
      increase in the MDA concentration. Studies in vitro demonstrated that
      cephaloridine stimulated the iron-catalyzed H2O2-dependent oxidation of
      porphyrinogens to porphyrins in the absence of either microsomes or mitochondria.
      Additionally, porphyrinogens were oxidized to porphyrins in an iron-dependent
      microsomal lipid peroxidation system. Moreover, porphyrinogens served as an
      effective antioxidant (EC50 approximately 1-2 microM) to lipid peroxidation.
      These results demonstrate that MMH and cephaloridine synergistically, as well as
      individually, promote increased oxidation of reduced porphyrins in the kidney and
      that this action may be mechanistically linked to oxidative stress elicited by
      these chemicals. Increased urinary porphyrin levels may, therefore, represent a
      sensitive indicator of oxidative stress in the kidney in vivo.

PMID- 8274158
TI  - 5-Ethynyluracil (776C85): inactivation of dihydropyrimidine dehydrogenase in
      vivo.
AB  - 5-Ethynyluracil (776C85), a potent, mechanism-based, irreversible inactivator
      (Porter et al., J Biol Chem 267:5236-5242, 1992) of purified dihydropyrimidine
      dehydrogenase (DPD, uracil reductase, EC 1.3.1.2), readily inactivated DPD in
      vivo. DPD was assayed in tissue extracts by measuring the release of 14CO2 from
      [2-14C]uracil with an improved method. Specific activities from 0.1 to > 1000
      U/mg protein were reproducibly measured. After rats were orally dosed with 20
      micrograms/kg 5-ethynyluracil, liver, intestinal mucosa, lung, and spleen DPD
      were inactivated by 83-94%. The dose required to inactivate rat liver, rat brain,
      and mouse liver DPD by 50% was 1.8, 11, and 8.9 micrograms/kg, respectively. Rat
      liver DPD was inactivated completely within 25 min after an oral dose of 500
      micrograms/kg 5-ethynyluracil. New DPD was synthesized with a half-time of 63 hr.
      We also developed an assay based on stoichiometric inactivation of DPD by 5
      ethynyluracil to measure 5-ethynyluracil in plasma samples. Samples containing 5
      ethynyluracil were incubated with rat liver extract for 24 hr at 12 degrees and
      then assayed for DPD. DPD activity decreased linearly with the concentration of 5
      ethynyluracil (between 0 and 20 nM 5-ethynyluracil). The assay could detect 5
      ethynyluracil at concentrations as low as 6 nM in human plasma and was not
      affected by high concentrations of uracil.

PMID- 8274159
TI  - Cytochrome P450 dependent N-hydroxylation of a guanidine (debrisoquine),
      microsomal catalysed reduction and further oxidation of the N-hydroxy-guanidine
      metabolite to the urea derivative. Similarity with the oxidation of arginine to
      citrulline and nitric oxide.
AB  - The microsomal N-hydroxylation of the strongly basic guanidinium group
      (debrisoquine) to N-hydroxyguanidine (N-hydroxydebrisoquine) and the
      retroreduction of the N-hydroxyguanidine are demonstrated for the first time. The
      reduction of the N-hydroxyguanidine by liver homogenates and hepatocytes is
      catalysed by a microsomal NADH-dependent system that is strongly inhibited by
      hydroxylamine or N-methylhydroxylamine. In the presence of these alternate
      substrates for the reductase the microsomal catalysed N-hydroxylation of
      debrisoquine is readily characterized. The oxidation was inhibited by antibodies
      against NADPH cytochrome P450 reductase and the role of the P450 monooxygenase
      was further verified by studies with partially purified and purified P450 2C3
      reconstituted systems. The transformation of N-hydroxydebrisoquine to the
      corresponding urea derivative was also detected in in vitro experiments with
      microsomal fractions and enriched P450 fractions as well as with flavin
      containing monooxygenase (FMO). Experiments with catalase, superoxide dismutase
      and H2O2 have shown that the H2O2 or O2-, respectively, formed from the
      respective enzyme and the substrate, apparently participated in the reaction.
      Whereas the N-hydroxylation of the guanidine involves the usual monooxygenase
      activity of cytochrome P450 the resultant N-hydroxyguanidine decouples
      monooxygenases (cytochrome P450, FMO) and the H2O2 and, above all, O2- thus
      formed transform the N-hydroxyguanidine further to the corresponding urea
      derivative. The possibility for the N-hydroxylation of non-physiological
      guanidines to N-hydroxyguanidines and subsequent oxidative conversion to the
      respective urea is comparable to the physiological transformation of arginine to
      citrulline via N-hydroxyarginine with the liberation of nitric oxide (endothelial
      derived relaxing factor) and could, therefore, contribute to the efficacy of
      drugs containing guanidine and similar functional groups.

PMID- 8274160
TI  - Effect of sodium orthovanadate on the hepatobiliary clearance of rose bengal in
      streptozotocin-induced diabetic rats.
AB  - Sodium orthovanadate is known to promote glucose uptake in muscle and adipose
      tissues and has been suggested as a possible oral hypoglycemic agent. In
      addition, insulin-dependent diabetes has been shown to alter the hepatobiliary
      clearance of several drugs in rats. This study has determined whether
      orthovanadate, like insulin, can reverse diabetes-induced changes in the biliary
      excretion of endogenous bile acids and in the hepatobiliary clearance of rose
      bengal. Six groups of male Sprague-Dawley rats were used; normal, insulin-treated
      normal, vanadate-treated normal, diabetic, insulin-treated diabetic, and vanadate
      treated diabetic. Diabetes was induced by injection of streptozotocin (45 mg/kg,
      i.v.). One week later, insulin (2-4 U/day, s.c.) and sodium orthovanadate (877 +/
      82 mumol/kg/day, p.o.) treatments were initiated. After 4 weeks, the clearance
      and biliary excretion of rose bengal (60 mumol/kg, i.v.) were determined for 3
      hr. Bile flow rate, rose bengal excretion, and excretion of endogenous bile acids
      were unchanged in the two treated normal groups and in the insulin-treated
      diabetic rats. These parameters were increased in untreated diabetic and vanadate
      treated diabetic rats as compared with normal. Pharmacokinetic analyses indicated
      that total and biliary clearances of rose bengal were increased in diabetic rats
      and that orthovanadate did not reverse these changes. However, liver weight and
      serum glucose concentrations were reduced by orthovanadate treatment. These data
      indicate that the oral insulinomimetic chemical sodium orthovanadate effectively
      reversed some, but not all, of the diabetes-induced alterations of hepatic
      function.

PMID- 8274161
TI  - Effect of BOF-4272 on the oxidation of allopurinol and pyrazinamide in vivo. Is
      xanthine dehydrogenase or aldehyde oxidase more important in oxidizing both
      allopurinol and pyrazinamide?
AB  - Allopurinol or pyrazinamide was administered to rats treated with BOF-4272 (a
      potent xanthine oxidase inhibitor) to investigate to what degree xanthine
      dehydrogenase participates in the oxidation of these agents. BOF-4272 markedly
      decreased the plasma concentration and the urinary excretion of both oxypurinol
      and 5-hydroxypyrazinamide. It also decreased the sum of the urinary excretion of
      allopurinol and oxypurinol and that of pyrazinamide and its metabolites, although
      it did not affect the sum of the plasma concentrations of allopurinol and
      oxypurinol at 105 min after administration of allopurinol or the plasma
      concentration of pyrazinamide during the period after the administration of
      pyrazinamide. These results suggested that BOF-4272 almost completely inhibited
      the oxidation of allopurinol and pyrazinamide and had some effect on the
      excretion and/or the tissue incorporation of these two compounds. Since the in
      vitro study demonstrated that BOF-4272 did not inhibit the activity of aldehyde
      oxidase, which oxidized both allopurinol to oxypurinol and pyrazinamide to 5
      hydroxypyrazinamide, the results suggested that xanthine dehydrogenase was the
      more important enzyme in converting allopurinol to oxypurinol and pyrazinamide to
      5-hydroxypyrazinamide.

PMID- 8274162
TI  - Bioactivation of S-methyl N,N-diethylthiolcarbamate to S-methyl N,N
      diethylthiolcarbamate sulfoxide. Implications for the role of cytochrome P450.
AB  - Diethyldithiocarbamate (DDTC), diethyldithiocarbamate methyl ester (DDTC-Me), S
      methyl N,N-diethylthiolcarbamate (DETC-Me) and S-methyl N,N-diethylthiolcarbamate
      sulfoxide (DETC-MeSO) are all metabolites of disulfiram. All inhibit rat liver
      low Km aldehyde dehydrogenase (ALDH) in vivo, with the order of potency being
      DETC-MeSO > DETC-Me > DDTC-Me > DDTC. Studies were carried out both in vivo and
      in vitro to further investigate the role of bioactivation as a requirement for
      the action of disulfiram as a liver ALDH inhibitor. The cytochrome P450 inhibitor
      1-benzylimidazole (NBI) was employed as a pharmacological tool to study the
      metabolism of DETC-Me to DETC-MeSO. Administration of NBI to rats prior to DETC
      Me treatment blocked the inhibition of liver mitochondrial low Km ALDH by DETC
      Me. This was accompanied by an increase in plasma DETC-ME and a decrease in
      plasma DETC-MeSO. Pretreatment of rats with NBI prior to DETC-MeSO administration
      did not block the inhibition of liver mitochondrial low Km ALDH by DETC-MeSO. In
      in vitro studies, the inclusion of NBI in an incubation containing rat liver
      microsomes, mitochondria and an NADPH-generating system blocked the formation of
      DETC-MeSO and inhibition of liver mitochondrial low Km ALDH by DETC-Me. DETC-MeSO
      was found to be a potent inhibitor of rat liver mitochondrial low Km ALDH both in
      vivo and in vitro. The data suggest that the metabolism of DETC-Me to DETC-MeSO
      is mediated by cytochrome P450, and that inhibition of cytochrome P450 by
      inhibitors such as NBI block the inhibition of low Km ALDH by DETC-Me.

PMID- 8274163
TI  - Role of flavin-dependent monooxygenases and cytochrome P450 enzymes in the
      sulfoxidation of S-methyl N,N-diethylthiolcarbamate.
AB  - Disulfiram is bioactivated to S-methyl N,N-diethylthiolcarbamate sulfoxide (DETC
      MeSO), the metabolite proposed to be responsible for the action of disulfiram as
      an aldehyde dehydrogenase inhibitor. This bioactivation process includes a
      reduction, an S-methylation, and two successive oxidations. Sulfur-containing
      functional groups are substrates for cytochrome P450 enzymes or flavin-containing
      monooxygenases (FMO). In the present study, we investigated the contribution of
      these monooxygenases to the formation of DETC-MeSO from its immediate precursor S
      methyl N,N-diethylthiolcarbamate (DETC-Me). Liver microsomes obtained from mature
      male rats were incubated with DETC-Me. The formation of DETC-MeSO was blocked
      completely by solubilization of the microsomes with the detergent Emulgen 911, or
      by the presence of the cytochrome P450 inhibitor 1-benzylimidazole. However,
      thermal-inactivation of FMO resulted in only a partial loss in DETC-MeSO
      formation. Liver microsomes from phenobarbital-treated rats showed a 4- to 5-fold
      increase in the rate of formation of DETC-MeSO, compared with controls. Liver
      microsomes from pyrazole-treated rats showed a 50% decrease in the sulfoxidation
      of DETC-Me compared with controls. In a purified reconstituted system, cytochrome
      P450 2B1 (CYP2B1) catalyzed the formation of DETC-MeSO at a rate of 51 nmol DETC
      MeSO formed/min/nmol cytochrome P450. Antibodies to CYP2B1 caused a 60%
      inhibition of DETC-MeSO formation by liver microsomes from phenobarbital-treated
      rats. These results suggest that in male rat liver microsomes, cytochrome P450
      plays a major role in catalyzing the sulfoxidation of DETC-Me, whereas FMO plays
      a minor role (< 10%). Also, in liver microsomes from phenobarbital-treated rats,
      CYP2B1 is the major catalyst for the sulfoxidation of DETC-Me.

PMID- 8274164
TI  - Differential susceptibilities of the prosthetic heme of hemoglobin-based red cell
      substitutes. Implications in the design of safer agents.
AB  - One approach to the development of an effective red cell substitute has been
      chemical modification of human hemoglobin to optimize oxygen transport and plasma
      half-life. Human hemoglobin A0 and two of these modified hemoglobins, one
      prepared from the cross-linking of the alpha-chains at lysine residue 99 by
      bis(3,5-dibromosalicyl)fumarate (Hb-DBBF) and the other by acylation of lysine
      residue 82 of the beta-chain by mono-(3,5-dibromosalicyl)fumarate (Hb-FMDA), were
      tested by HPLC for their susceptibility to oxidative damage caused by H2O2. Such
      oxidative insult may occur during ischemia and reperfusion of tissues after
      transfusion of red cell substitutes to patients with hypovolemic shock and
      trauma. Hb-DBBF was extremely susceptible to damage of its heme and protein
      moieties with stoichiometric amounts of H2O2, whereas Hb-FMDA was highly
      resistant, even at 10-fold molar excess and at an acidic pH of 4.7. Hemoglobin A0
      was of intermediate susceptibility, exhibiting alteration of heme and protein
      moieties at acidic but not neutral pH. Since the degradation of heme can release
      the potentially toxic agent iron, Hb-FMDA may be a more promising candidate than
      Hb-DBBF for development as a red cell substitute. A similar approach may be used
      to assess the susceptibility of other hemoglobin-based red cell substitutes to
      oxidative damage in order to determine the molecular basis of heme and protein
      alteration.

PMID- 8274165
TI  - Effect of sodium tanshinone IIA sulfonate in the rabbit myocardium and on human
      cardiomyocytes and vascular endothelial cells.
AB  - Sodium tanshinone IIA sulfonate (STS) is a derivative of tanshinone IIA. The
      latter is a pharmacologically active component isolated from the rhizome of the
      Chinese herb Salvia miltiorrhiza. Liquid chromatographically pure STS was found
      to reduce myocardial infarct size by 53.14 +/- 22.79% relative to that in the
      saline control in a rabbit 1 hr-ischemia and 3 hr-reperfusion model. This effect
      was comparable to that of Trolox (a better characterized antioxidant serving as a
      reference cytoprotector), which salvaged the myocardium in the same infarct model
      by 62.13 +/- 18.91%. Also, like Trolox, STS did not inhibit oxygen uptake by
      xanthine oxidase (XO), a key enzyme in free radical generation. However, in
      contrast to Trolox, STS significantly prolonged the survival of cultured human
      saphenous vein endothelial cells but not human ventricular myocytes in vitro when
      these cells were separately exposed to XO-generated oxyradicals. Note that the
      endothelium is recognized to be a key site of oxidant generation and attack. Our
      findings in vitro and in vivo support the interpretation that STS is a
      cardioprotective substance, and that it may exert a beneficial effect on the
      clinically important vascular endothelium.

PMID- 8274166
TI  - Stereoselective S-oxygenation of an aryl-trifluoromethyl sulfoxide to the
      corresponding sulfone by rat liver cytochromes P450.
AB  - Toltrazuril sulfoxide (TZR.SO) is the metabolite of the antiparasitic drug
      toltrazuril (TZR; 1-methyl-3-[3-methyl-4-[4-[trifluoromethyl]thio]phenoxy]phenyl-
      1,3,5-triazine-2,4,6(1H,3H,5H)-trione). The results of the present paper
      demonstrate that TZR.SO was metabolized by rat liver microsomes to the
      corresponding sulfone (TZR.SO2). The reaction was mediated almost exclusively by
      different cytochromes P450, the most active being cytochromes P450 3A. TZR.SO
      exists as a racemic mixture; when each enantiomer was incubated separately in the
      presence of untreated rat liver microsomes, a 7.3-fold difference in the rate of
      S-oxygenation was found, indicating a marked substrate enantioselectivity for the
      reaction.

PMID- 8274167
TI  - [Aln1 and Aln5--new oligonucleotide primers for Alu-PCR analysis of human DNA].

PMID- 8274168
TI  - [Interaction of the outer membrane pore-forming protein of Yersinia
      pseudotuberculosis with lipid A and its synthetic analogs].
AB  - Interaction of the major outer membrane protein form Yersinia pseudotuberculosis
      with lipid A was investigated by intrinsic fluorescence, CD spectroscopy and CsCl
      gradient centrifugation methods. The protein was shown to have two independent
      binding sites with an association constant 6.1 x 10(4) M-1. The interaction
      depends on both the type of the glycoside bond and hydrophilic--hydrophobic
      balance of the glycolipid molecule.

PMID- 8274169
TI  - [Preparation of monoclonal antibodies to phenobarbital].
AB  - Monoclonal antibodies to phenobarbital have been developed. Spleen cells of
      BALB/c mouse immunized with conjugate keyhole limpet haemocyanin and
      phenobarbital were fused with P3-X63-Ag8.653 mouse myeloma cells. Three
      monoclonal antibodies, selected by indirect ELISA, were produced in mouse ascite
      fluids, purified and analyzed. Antibody 1A9 was selected for use in immunoassay,
      its association constant being 1.6 x 10(9) M-1.

PMID- 8274170
TI  - [Determination of cardenolides in Digitalis lanata by a solid-phase immunoenzyme
      method].
AB  - A competitive solid-phase EIA technique using high-affinity digoxin-specific
      monoclonal antibodies has been developed to determine cardenolides in Digitalis
      lanata. The test-system can detect digoxin and closely related compounds in
      concentration of 0.1 nmol/ml. The content of cardenolides, tested by ELISA,
      correlated well with the total content of digoxin, deslanoside C and lanatoside C
      as analysed by HPLC. The test-system is useful in estimating the productivity of
      large series and samples of tissue clones of Digitalis lanata.

PMID- 8274171
TI  - [Analysis of the secondary structure of the regulatory region of mRNA of the
      Escherichia coli rpsA gene].
AB  - The rpsA gene of E. coli coding for the ribosomal protein S1 was inserted into
      the plasmid pGEM-3Z under the control of a T7 promoter. The resulted plasmid was
      used for mRNA preparation in vitro. The toeprint analysis of the rpsA mRNA
      revealed a strong S1 dependence: 30S ribosomal subunits lacking S1 were inactive
      in the 30S initiation complex formation; addition of the free S1 restored
      subunits' ability to bind mRNA; a molar excess of the free S1 over ribosomes was
      inhibitory. The secondary structure of the rpsA mRNA in the vicinity of the
      initiation codon was probed with the use of specific ribonucleases. Basing on the
      experimental data obtained we suggest a model for the structural organisation of
      the rpsA mRNA translation initiation region.

PMID- 8274172
TI  - [3'-Fluoro-deoxythymidine-5-fluorophosphate--an effective inhibitor of
      reproduction of human immunodeficiency virus in cell cultures].

PMID- 8274173
TI  - Assessment of MRI criteria for a diagnosis of MS.
AB  - To test the reliability of four previously proposed MRI criteria for the
      diagnosis of MS, we reviewed 1,500 consecutive brain scans for the presence,
      number, size, and location of areas of increased signal (AIS) on proton-density
      and T2-weighted images, unaware of the patients' clinical presentations and ages.
      This series included 134 subjects with a clinical diagnosis of MS. Relying
      exclusively on the presence of at least three or four AIS for a positive
      diagnosis of MS resulted in high sensitivity (90% for three AIS and 87% for four)
      but inadequate specificity (71% for three AIS and 74% for four) and positive
      predictive value (23% for three AIS and 25% for four). If one of these lesions
      was required to border the lateral ventricles, specificity was 92% and positive
      predictive value was 50% at a sensitivity of 87%. Using the Fazekas criteria (at
      least three AIS and two of the following features: abutting body of lateral
      ventricles, infratentorial lesion location, and size > 5 mm) led to a further
      highly significant improvement of specificity (96%; p = 0.0000) and increase of
      the positive predictive value (65%) at the expense of a less significant decrease
      in sensitivity (81%; p < 0.01).

PMID- 8274174
TI  - Oligonucleotide analogs containing dephospho-internucleoside linkages.

PMID- 8274175
TI  - Effect of acute ethanol dosage on nucleotide levels in the rat jejunum:
      relationship to protein synthesis.
AB  - The effects of an acute dose of ethanol (75 mmol/kg body weight; i.p.) on
      nucleotide levels in the rat jejunum were investigated. After 2.5 hr, ethanol
      exposure significantly reduced ATP and GTP contents and increased ADP and GDP
      contents. There were no statistically significant effects on pyrimidine
      nucleotides or IMP. Fractional rates of jejunal protein synthesis were also
      significantly reduced by ethanol. It was concluded that purine nucleotides are
      sensitive to acute ethanol administration in the rat jejunum. This may explain
      why rates of protein synthesis are decreased in the jejunum, as these nucleotides
      play a key role in polypeptide formation.

PMID- 8274176
TI  - Lack of effect of acetaldehyde on the cardiovascular system in rats.
AB  - The present study was designed to evaluate the kinetics of acetaldehyde (ACT) and
      and its action on the cardiovascular system in rats. ACT (3, 6, 12 mg/kg i.p.)
      causes accumulation of this metabolite in the blood, at a concentration
      corresponding to that obtained from ethanol metabolism after its administration
      in doses of 1, 2, 4 g/kg p.o., respectively. After intraperitoneal injection of
      ACT there were no significant changes in blood pressure and heart rate in
      comparison to the control group. It appears that, in rats, ACT has no influence
      on the function of the cardiovascular system after the ingestion of ethanol.

PMID- 8274177
TI  - Problems involved in the determination of endogenous acetaldehyde in human blood.
AB  - Little is known about the possible existence of endogenous acetaldehyde in human
      blood. This has partly been due to analytical difficulties preventing accurate
      determination of blood acetaldehyde levels with and without the presence of
      ethanol. In the present study the possible existence of endogenous acetaldehyde
      in human blood was investigated with headspace gas chromatography using three
      different procedures for the treatment of samples: (1) no treatment of whole
      blood, cells, or plasma (direct headspace method), (2) hemolysation, and (3)
      perchloric acid (PCA) precipitation, prior to the headspace determinations. In in
      vitro experiments, with the direct headspace and the hemolysation methods, higher
      acetaldehyde peaks were obtained depending on the headspace incubation time,
      temperature and ethanol concentration. Both methods displayed about the same
      values of acetaldehyde in blood cells, ranging between 0 and 40 microM, at
      incubation times between 15 and 180 min, an incubation temperature of 65 degrees
      C, and ethanol concentrations less than 5 microM. Less acetaldehyde formation (0
      15 microM) was obtained with PCA precipitates of whole blood and cell components.
      Very low acetaldehyde levels (0-1 microM) were obtained in the supernatants
      without precipitates from either whole blood or cells after headspace
      equilibration. Substantially less acetaldehyde was formed in plasma preparations
      than with whole blood and cell fractions. In human experiments, the disturbance
      of endogenous or exogenous ethanol was minimized by separating and washing the
      blood cells followed by PCA treatment. No differences in acetaldehyde
      concentrations were observed in blood samples taken before, during, or after
      ethanol intoxication (1.5 g/kg dose) of four healthy non-alcoholic
      volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274178
TI  - Relationship between ethanol-related diseases and nutritional status in
      chronically alcoholic men.
AB  - Two-hundred and fifty chronically alcoholic men (mean age, 41 +/- 11 years)
      entering an alcoholism treatment program were studied. Detailed clinical history,
      nutritional assessment and measurement of muscle strength by electronic myometer
      were performed in each case. In addition, hepatic ultrasonography and liver
      biopsy, echocardiography and radionuclide cardiac scanning, and
      electrophysiologica testing of peripheral nerves were performed when there was
      clinical evidence of liver disease, cardiomyopathy or neuropathy, respectively.
      Alcoholic cirrhosis was diagnosed in 20 cases, skeletal myopathy in 117, dilated
      cardiomyopathy in 20 and peripheral neuropathy in 41 cases. No patients with
      chronic myopathy or cardiomyopathy showed either clinical or laboratory evidence
      of malnutrition. Patients with cirrhosis showed a significantly lower lean body
      mass than controls (P = 0.03) and significantly lower nutritional protein levels
      than those alcoholics without cirrhosis. Alcoholics with peripheral neuropathy
      had significantly lower anthropometric parameters and nutrition protein levels
      than their counterparts (P < 0.001). However, in the multivariate analysis, the
      only independent factor for developing these complications of alcoholism was the
      total lifetime dose of ethanol (P < 0.001). We conclude that alcohol-related
      diseases are common in asymptomatic alcoholic men and these diseases appear to be
      due to an accumulative toxic effect of ethanol. Age and nutritional status do not
      seem to play a part in the development of such diseases.

PMID- 8274179
TI  - Nutritional status in chronically alcoholic men from the middle socioeconomic
      class and its relation to ethanol intake.
AB  - To determine the relationship between nutritional status and ethanol consumption,
      250 chronically alcoholic men (mean age 41 +/- 11 years) entering an alcoholism
      treatment program were studied. A control group of 100 male volunteers (mean age
      40 +/- 10 years) was also evaluated. Detailed clinical history, laboratory
      analysis and nutritional status assessment were carried out in each case and
      control. In addition, ethanol-related diseases such as liver disease, chronic
      pancreatitis, cardiomyopathy, myopathy and peripheral neuropathy were ruled out
      in all patients. The mean daily ethanol consumption of the alcoholics was 235 +/-
      62 g over an average of 19 years. All of them belong to a very stable, middle
      class working group of men. Only 25 (10%) alcoholics showed evidence of energy
      malnutrition, 15 (6%), of protein malnutrition, and 6 (2%) of both. In the
      multivariate analysis, the only independent factors for the development of
      malnutrition were the total lifetime dose of ethanol and calorie intake (ethanol
      excluded) (P < 0.01; both), as well as cirrhosis (P < 0.01) when protein
      malnutrition was considered. Alcoholic cirrhosis was diagnosed in 20 cases,
      skeletal myopathy in 117, dilated cardiomyopathy in 20 and peripheral neuropathy
      in 41. When patients with ethanol-related diseases were excluded, no significant
      differences in nutritional parameters were observed between chronic alcoholics
      and controls. We conclude that malnutrition is not as frequent as previously
      thought in middle socioeconomic class male alcoholics and its existence may be
      considered as another consequence of ethanol intake or secondary to the alcohol
      related diseases.

PMID- 8274180
TI  - Chronic ethanol exposure increases lipopigment accumulation in human heart.
AB  - The amount and distribution of myocardial lipopigments ('age pigments') were
      studied in alcoholic and control human hearts, to test the hypothesis of ethanol
      induced long-term oxidative damage in myocardium. The amount of myocardial
      lipopigments was measured by image analysis in six men (age 34-60 years) who had
      a history of chronic alcohol misuse and who died of acute ethanol intoxication,
      and in their age-matched, non-alcoholic controls. Lipopigmentation in the
      intoxication cases was 33.5 +/- 2.8% (mean +/- SEM) higher compared to the
      controls in the eight myocardial areas studied (P < 0.001). A linear correlation
      of myocardial lipopigmentation with age was noticed in both the intoxication
      group (R = 0.894) and the controls (R = 0.927). The amount of lipopigments varied
      largely from one myocardial area to another, being highest in the most strained
      areas (left ventricle, interventricular septum). The accumulation of lipopigments
      is considered a marker of oxidative stress and ageing in the myocardium. The
      results support the role of free radical-induced oxidative stress in the
      pathogenesis of ethanol-induced cardiac abnormalities.

PMID- 8274181
TI  - Mineral metabolism, osteoblastic function and bone mass in chronic alcoholism.
AB  - The role of ethanol as a risk factor for osteopenia was studied in alcoholic
      subjects without liver cirrhosis. The study was carried out in 58 male subjects
      classified into three groups: (1) 26 heavy drinkers, alcohol intake more than 100
      g ethanol/day for more than 10 years; (2) 13 moderate drinkers, 60-100 g
      ethanol/day; (3) 19 healthy non-drinkers who served as control subjects. None of
      the drinkers had liver cirrhosis (normal clinical and biochemical data and/or
      liver biopsy). Mineral metabolism and serum bone Gla-protein (BGP) were studied
      while they were active drinkers and after they had abstained from ethanol for 7
      days. Bone mineral density (BMD) was determined at the beginning of the study.
      Osteopenia was observed in 23% of the heavy drinkers. We found a significant
      inverse correlation between BMD and an index of cumulative alcohol intake. Heavy
      and moderate drinkers had significantly lower mean BGP values (1.6 +/- 0.4 and
      1.9 +/- 0.3 ng/ml) (P < 0.01 for both) than controls (3.5 +/- 0.4 ng/ml); these
      values increased significantly (2.9 +/- 0.4 ng/ml; P < 0.01) after 7 days of
      abstinence. The data show that chronic ethanol ingestion can induce osteopenia
      regardless of the absence of liver cirrhosis, and that some relationship can be
      expected between the amount and duration of ethanol consumption and the degree of
      bone loss. The low serum BGP levels in drinkers are reversible upon withdrawal of
      ethanol, suggesting that reduction of osteoblastic activity is probably the main
      factor responsible for alcohol-associated bone disease.

PMID- 8274182
TI  - Prevalence of cholelithiasis in alcoholic and genetic haemochromatotic cirrhosis.
AB  - The prevalence of cholelithiasis and possible related factors was evaluated in
      350 consecutive patients with alcoholic cirrhosis (218 cases, 174 male and 44
      female, mean age 58 +/- 9 years) or genetic haemochromatotic cirrhosis (132
      cases, 115 male and 17 female, mean age 53 +/- 10 years). At enrollment patients
      with alcoholic cirrhosis were significantly older than those with genetic
      haemochromatotic cirrhosis (P < 0.01), and their clinical status was more severe
      (Child's class B/C in 99 alcoholic cirrhosis cases versus 27 genetic
      haemochromatotic cirrhosis cases, P < 0.01). The overall frequency of
      cholelithiasis was 31% (67 cases) in the alcoholic cirrhosis group and 30% (40
      cases) in the genetic haemochromatotic cirrhosis group, without differences
      according to gender, classes of age (< or = 49, 50-59, > or = 60 years), or HBsAg
      positivity in either group. In addition, in the genetic haemochromatotic
      cirrhosis group the presence of diabetes (45 cases), alcohol misuse (38 cases)
      and beta-thalassemia trait (13 cases) did not influence the prevalence of
      cholelithiasis. Body mass index, serum cholesterol and triglycerides, and the
      severity of the underlying liver disease (Child's class) did not distinguish
      patients with or without cholelithiasis. In conclusion, the frequency of
      cholelithiasis was high in both alcoholic cirrhosis and genetic haemochromatotic
      cirrhosis, and was three times higher than that reported in controls from the
      general population of the same area.

PMID- 8274183
TI  - Question-asking strategies in abstinent alcoholics: a study of learning
      potential.
AB  - The question-asking strategies of 90 Finnish alcoholics were measured on a
      Vygotskian version of the Twenty Questions procedure. There were two questions to
      analyse: (1) can the performance of alcoholics be improved by means of
      instruction in question-asking; and (2) how does the duration of abstinence
      affect test performance? The results indicated that instruction had a positive
      effect on the performance of alcoholics. The duration of abstinence had no
      general effect; its effect was evident only in one type of question, i.e.,
      pseudoconstraint questions. There were marked interindividual differences in both
      the pre-test and the post-test. About 15% of the subjects showed no noticeable
      improvement in their post-test performance in spite of the instruction they
      received.

PMID- 8274184
TI  - The kindling hypothesis: further evidence from a U.S. national study of alcoholic
      men.
AB  - A sample of 6818 alcoholic men participating in a short in-patient detoxification
      episode was studied to examine the kindling effect of repeated prior alcohol
      withdrawals on occurrence of seizures or severe withdrawal problems observed
      during the hospitalization. Subjects studied were hospitalized in one of 172 U.S.
      Department of Veterans Affairs medical centers. Patients with seizures and
      withdrawal problems had more prior detoxifications and other alcohol-specific
      hospitalizations. They were also more likely to be later readmitted for an
      alcoholism diagnosis. Patients with withdrawal problems during the detoxification
      episode studied were more likely to have such problems again as well as seizures
      during the readmission; those with seizures during the index detoxification were
      more likely to have repeated seizures during the readmission. These results
      confirm the kindling effect in a large, multi-site patient sample and suggest
      that alcohol detoxification programs may need to consider anticonvulsant therapy
      in patients with many prior detoxifications or withdrawals.

PMID- 8274185
TI  - An inventory of the alcohol research literature.
AB  - This paper provides an inventory of the literature on alcohol research. The aim
      is to provide the readers of this literature with data on the quantity and types
      of papers published. For this purpose, over 4000 scientific papers on biomedical
      and social aspects of alcohol consumption, which had been collected in our
      Alcohol Documentation Centre over the past 2 years, were surveyed. They were
      classified according to three criteria: (1) the subject under investigation, (2)
      the type of study, and (3) whether the study concerned normal consumption,
      alcohol misuse or both. Furthermore, information is given on sources of alcohol
      research literature, authorship, and countries of origin.

PMID- 8274186
TI  - Dietary fatty acids and alcohol: effects on cellular membranes.

PMID- 8274187
TI  - Does endogenous glycosylation prevent the use of mouse monoclonal antibodies as
      cancer therapeutics?
AB  - Monoclonal antibodies have many potential therapeutic benefits. However, when
      applied to humans, mouse monoclonal antibodies have several disadvantages. Here
      Carl Borrebaeck and colleagues describe a strategy to overcome the anti-Gal
      activity, thought to be one of the reasons why mouse mAbs have a limited half
      life.

PMID- 8274188
TI  - S-type mammalian lectins in allergic inflammation.
AB  - Our understanding of the mechanisms of allergic disease is continuously
      influenced by new developments in the bio-medical sciences. The studies of
      glycoconjugates and animal lectins have emerged as an exciting new frontier. One
      family of animal lectins, soluble lactose-binding lectins, has been studied
      extensively by a number of laboratories. Evidence is mounting that members of
      this family of lectins exist in the extracellular space and may be capable of
      affecting functions of various cells. In this article Fu-Tong Liu presents a
      revised view of allergic inflammation with emphasis on the modulatory effect of
      soluble lectins on mast-cell function.

PMID- 8274189
TI  - Natural history of HLA expression during tumour development.
AB  - HLA expression is frequently altered in tumours compared to the tissue from which
      they originate. Given the central role of MHC products in the restriction of T
      cell recognition, regulation of tumour HLA expression might be a strategy for the
      evasion of immune surveillance by the malignant cells. Federico Garrido, Peter
      Stern and colleagues present data from a variety of tumour types, suggesting that
      HLA class I alterations may occur at a particular step between the development of
      an in situ lesion and an invasive carcinoma.

PMID- 8274190
TI  - Role of heparan sulfate in immune system-blood vessel interactions.
AB  - Heparan sulfate proteoglycan, a component of endothelial cell membranes and
      extracellular matrices, is involved in a number of the critical functions of
      endothelium and of antigen-presenting cells. This review discusses how heparan
      sulfate is released from endothelial cells during inflammation, how the loss of
      heparan sulfate potentially alters endothelial cell physiology, and how the
      presence of heparan sulfate in a soluble form might regulate the functioning of
      lymphocytes at sites of inflammation.

PMID- 8274191
TI  - Are lymphocytes concerned with our definition of idiotypes?
AB  - For some, idiotypes are interesting as markers of individual molecules, providing
      the basis for a taxonomy of B- and T-cell clones. For us, idiotypes are
      components of a larger network structure of variable regions, and their shapes
      are of significance because they establish connectivity. Each unique specificity
      per se is less interesting, for it is interchangeable without altering network
      organization. These issues are critical for delineating concepts of autoimmunity
      and for choosing between 'nonspecific' and 'targeted' approaches of
      immunoglobulin therapy in autoimmune diseases.

PMID- 8274192
TI  - Scope and perspectives of intravital microscopy--bridge over from in vitro to in
      vivo.
AB  - As observations in vitro become more sophisticated, it is increasingly important
      to be able to assess their relevance to the intact animal. Intravital microscopy
      provides an advanced set of tools for the dissection of the in vivo situation.

PMID- 8274193
TI  - Saying the 'S' word in public.
AB  - The mechanism by which self-reactive, peripheral lymphocytes are prevented from
      causing overt autoimmune disease is the subject of much debate. A recent meeting
      examined the evidence to support a role for T-cell mediated suppression in
      maintenance of peripheral tolerance.

PMID- 8274194
TI  - A possible role for bcl-2 in regulating T-cell memory--a 'balancing act' between
      cell death and survival.
AB  - One of the central questions in T-cell immunity is how the generation of T-cell
      memory may proceed simultaneously with the maintenance of T-cell homeostasis. In
      this article, we present a hypothesis that the regulation of bcl-2 gene
      expression within the activated CD45RO+ T-cell population may be one of the key
      factors in the balance between death and survival of these activated mature T
      cells, both in vitro and in vivo.

PMID- 8274195
TI  - Retroviruses, apoptosis and autogenes.
AB  - Autoimmunity and autoimmune disease are not the same. Autoimmunity is a normal
      consequence of aging, potentially reversible and possibly physiological.
      Autoimmune disease is dependent on genetic, viral, hormonal and
      psychoneuroimmunological factors. Aside from the apparently normal regulation of
      autoimmune responses by immune response genes, little is known about other
      genetic factors. Here, Norman Talal and John Mountz propose the term autogene to
      describe non-MHC genes which directly or indirectly interfere with important
      immunoregulatory actions. When mutated or otherwise genetically altered (e.g. by
      retrotransposon insertion), these genes predispose to immune dysregulation,
      lymphoproliferation and autoimmunity.

PMID- 8274196
TI  - Tumor immunity as autoimmunity: tumor antigens include normal self proteins which
      stimulate anergic peripheral T cells.
AB  - Oncogenic transformation is often accompanied by a significant overproduction of
      otherwise normal cellular proteins. Because of the low expression of such self
      components during thymic development, T cells specific for these antigens can
      escape deletion and progress to the periphery. In this viewpoint, Giorgio
      Parmiani discusses the concept that these T cells can be harnessed to provide an
      effective anti-tumor response.

PMID- 8274197
TI  - Structural compartmentalization of MHC class II signaling function.
AB  - Major histocompatibility complex (MHC) class II molecules are critical
      restricting elements in the generation of thymus-dependent immune responses.
      Recent studies indicate that in addition to providing a composite epitope for
      recognition by T-cell antigen receptors, MHC class II molecules function in
      signal transduction through interaction with other cellular proteins. Mutational
      analyses indicate that structural information necessary for these functions is
      compartmentalized in different aspects of the molecular complex. Here, William
      Wade and colleagues review the structural basis of this MHC class II function as
      defined in the I-A alpha and -beta chains.

PMID- 8274198
TI  - X-linked agammaglobulinemia--gene cloning and future prospects.
AB  - The btk gene has recently been identified as the causative gene in X-linked
      agammaglobulinemia (XLA). This has opened up many new possibilities for the
      treatment of this B-cell immunodeficiency. Christine Kinnon and colleagues review
      the high degree of sequence of homology of btk to the non-receptor tyrosine
      kinases and speculate on putative roles for this gene in B-cell development.

PMID- 8274199
TI  - How to write the recent history of immunology--is the time really ripe for a
      narrative synthesis?
AB  - In June 1992 historians and immunologists met at the International School of
      Biological Sciences on Ischia, Italy to discuss aspects of the recent history of
      immunology. This paper takes issue with some of the historiographical
      recommendations in the report from the meeting by Horace F. Judson and Ian Mackay
      ('History in the Bay of Naples', Immunology Today, November 1992).

PMID- 8274200
TI  - MHC heterozygosity and autoimmunity.

PMID- 8274201
TI  - The crystal and molecular structure of trichosanthin at 2.6 A resolution.
AB  - The crystallographic refinement of trichosanthin has been performed at 2.6 A
      resolution. The crystal and molecular structure of trichosanthin is described in
      detail in this paper. On summarizing the regularity of the amino acid sequences
      of eight kinds of ribosome inactivating proteins and combining with the crystal
      and molecular structure of trichosanthin, fifteen most conservative amino acid
      residues are analyzed. It is found that four most conservative polar amino acid
      residues Gln156, Glu160, Arg163 and Glu189 gather on the molecular surface on the
      boundary of the large and small domains, thus forming the active center of the
      protein molecule.

PMID- 8274202
TI  - Expression of human factor IX cDNA in mice by implants of genetically modified
      skin fibroblasts from a hemophilia B patient.
AB  - Double-copy retroviral vector containing human factor IX cDNA driven by human
      cytomegalovirus enhancer-promoter was constructed. The vector was introduced into
      the amphotropic packaging cell line PA317. The recombinant virus produced in
      PA317 was used to transduce skin fibroblasts from a hemophilia B patient. The
      infected cells produced high levels of biologically active human factor IX at a
      rate of 3420 ng/10(6) cells/24 h. These cells were embedded in a collagen matrix
      and implanted into the peritoneal cavity or subcutaneous space of mice. It was
      demonstrated that human factor IX was produced by the implants for at least 12
      days in vivo, reaching a peak of 105 ng/ml plasma. Over 90% of the protein was
      functionally active. This technique has the potential to be developed into a new
      approach for gene therapy for hemophilia B.

PMID- 8274203
TI  - Molecular study on the chromosome 15 breakpoints in the translocation t(15; 17)
      in acute promyelocytic leukemia (APL).
AB  - Chromosomal translocation t(15; 17) is a specific marker of acute promyelocytic
      leukemia (APL). In this study, molecular cloning of the t(15; 17) breakpoint was
      carried out in a Chinese APL patient. It has been shown that the retinoic acid
      receptor alpha (RARA) gene, normally located on chromosome 17, was fused with a
      new transcription unit PML, normally localized on chromosome 15. We have
      subsequently cloned a portion of the PML gene and generated a panel of probes. A
      PML gene rearrangement was detected in 33 out of 36 APL cases studied. 24
      rearrangements were clustered in a 4.4 kb region, designated here as PMLbcr1
      whereas 9 rearrangements were concentrated in a 6.5 kb region, defining another
      breakpoint cluster region (PMLbcr2). These two types of rearrangement constitute
      the basis for the heterogeneity of the PML-RARA fusion gene and its possible
      biological significance remains to be explored.

PMID- 8274204
TI  - The effects of glutamate and GABA (gamma-amino-butyric-acid) on spontaneous
      acetylcholine release at the neuromuscular junction in Xenopus laevis embryo cell
      cultures.
AB  - The miniature endplate currents (MEPC's) were recorded at the neuromuscular
      junction of Xenopus laevis embryo neuron-muscle co-cultured cells. These MEPC's
      were due to the spontaneous release of acetylcholine from the nerve terminal.
      After perfusion with glutamate (10 mumol/L), both frequency and amplitude of the
      MEPC's increased. After washing away of glutamate, this effect persisted. We
      named this phenomena "Long-Term Facilitation". GABA (20 mumol/L) on the other
      hand had an inhibitory effect on both frequency and amplitude of the MEPC's.
      After washing away of GABA, the MEPC frequency and amplitude increased. We named
      this effect "Post-Potentiation". Local perfusion experiments furthermore
      indicated that the effect of glutamate was restricted to the neuromuscular
      junction, the effect of GABA was restricted to the soma.

PMID- 8274206
TI  - [Ecogeographical distribution, utilization and protection of rare and precious
      traditional Chinese drug Changium smyrnioides Wolff].

PMID- 8274207
TI  - [Thin layer chromatographic fingerprint of Rhizomata of Coptis spp].
AB  - This paper introduces the use of optimized solvent system with twice-ascending
      development in twin trough chamber on TLC silica gel plate for the separation of
      protoberberine-type alkaloids contained in Rhizomata of Coptis spp. Nine to
      eleven spots including the main and the 'minor' alkaloids in the samples can be
      observed on the chromatograms obtained under controlled conditions. The
      fluorescence and UV-absorption TLC scanning profile can serve as fingerprint for
      the analysis of commercial samples of Rhizomata of Coptis spp.

PMID- 8274205
TI  - [Recent progress in the study of anti-PAF (platelet activating factor)
      constituents of medicinal herbs].
AB  - This paper deals with the recent progress in the study of anti-PAF constituents
      of medicinal herbs. The structural modification, synthesis of analogs and
      pharmacophore model are also introduced in brief.

PMID- 8274208
TI  - [Multivariate quantitative correlation analysis of chemical constituents of peony
      root in different collecting seasons].
AB  - Computer-aided multivariate quantitative correlation analysis was applied to the
      glucoside and benzoic acid contents of peony root in different collecting
      seasons. 4 independent and 11 dependent variables were taken to calculate the
      correlation coefficient and multi-correlation coefficient. The comparison of
      correlation coefficients shows that the contents are conditioned primarily by the
      ontogenetic stages in the plant itself and secondarily by external factors such
      as air temperature and rainfall, etc.

PMID- 8274209
TI  - [Cause of leaf yellowing of Amomum villosum Lour. from Yunnan and its
      prevention].
AB  - The results of the experiment showed that manganese deficiency in soil is one of
      the main causes of leaf yellowing of Amomum villosum and applying trace element
      fertilizer can make up deficiency. Manganese sulphate can effectively prevent the
      leaf yellowing.

PMID- 8274210
TI  - [Effect of processing on phospholipid of Dioscorea opposita Thunb].
AB  - A study of the chemical changes of phospholipid in crude and seven processed
      samples of Dioscorea opposita was carried out by molybdenum blue colorimetry and
      TLCS. The result shows that the total phospholipid content in the sample
      processed by honey bran comes out the highest (180.31 mg/100g).

PMID- 8274211
TI  - [Comparison of trace elements in muli before and after processing].
AB  - Determination and comparison of 34 kinds of trace elements in 5 samples of muli
      before and after processing have been conducted by ICP-AES. The result shows that
      all the elements have changed in contents.

PMID- 8274212
TI  - [Stability of liensinine injection].
AB  - The stability of liensinine injection was studied by accelarating test with
      classical isothermal method. Results of the study showed that the decomposition
      of the injection was found to be a first-order reaction. The activation energy
      was 75030 J.mol-1. The shelf life at 10 degrees C and 25 degrees C was predicted
      to be about 15 months and 3 months respectively. This experiment provides a
      reference for the storage of the injection.

PMID- 8274213
TI  - [Extraction of berberine hydrochloride from Mahonia bealei (Fort.) Carr].
AB  - The article reports the processing methods for extracting berberine hydrochloride
      from Mahonia bealei by means of regressive test. The result shows that
      A2B3C1D2E3F2 is the best way, namely, extractive solvent--0.5% sulfuric acid,
      salting out--24% salt, soaking temperature--25 degrees C, soaking time--48 hours,
      pH = 1.5, precipitation time--24 hours. The recovery is 1.45%-1.47%.

PMID- 8274214
TI  - [Chemical constituents of fresh bulbs of Fritillaria thunbergii Miq].

PMID- 8274215
TI  - [Chemical constituents of Eupolyphaga sinensis Walkre].

PMID- 8274216
TI  - [Analgesic effect and gastro-intestinal motility inhibitory action of 3-hydroxy-4
      methoxy-acetophenone from Cynanchum paniculatum (Bunge) Kitagawa].
AB  - 3-Hydroxy-4-methoxy-acetophenone (HMA) isolated from Cynanchum paniculatum was
      found to have analgesic effect and inhibitory action on the gastro-intestinal
      motility. The effect and action were equivalent to that of paeonol, HMA displayed
      a very low degree of antibacterial activity against Escherichia coli and Shigella
      flexneri.

PMID- 8274217
TI  - [A preliminary observation on the pharmacological effect of huoxue zhitong
      powder].

PMID- 8274218
TI  - [Blood-lipid decreasing action of total saponins of Panax notoginseng (Burk.)
      F.H. Chen].
AB  - Blood-lipid decreasing action of total saponins of Panax notoginseng was studied.
      The results showed that after the saponins were given po 100 mg/kg and 200 mg/kg
      to rats and quails, two high lipid model animals, for seven days, their TCH and
      TG were evidently decreased (P < 0.05).

PMID- 8274219
TI  - Multifunctional roles of glycosyl-phosphatidylinositol lipids.
AB  - The results presented here indicate that GPI lipids are a structurally and
      functionally diverse molecular family. Despite new detailed information on the
      structures of GPI-anchored proteins, there is relatively scant information on the
      structure of free-GPI. Thus, little is known of the relationships between GPI
      structures and the mechanism of their biological effects. For example, there is
      no distinction at the structural level between hormone-sensitive free-GPI and
      those that serve as precursors for protein-GPI. Nor is there precise biochemical
      data on the mechanism and importance of free-GPI in hormone signaling, or the
      signaling roles that GPI anchors play in protein function. The T-cell activation
      cascade is an ideal system for studying both forms of GPI and their derivatives.
      The study of GPI molecules in T lymphocytes offers the exciting possibility of
      addressing questions on the structure, function, genesis, and regulation of both
      free- and protein-GPI molecules in a single cell type. The detection of multiple
      protein-GPI and free-GPI forms, and of hormone-sensitive GPI, provides the first
      approach to these issues. For the moment, the potential for biochemical signaling
      by intact GPI or its metabolites is enormous. If significant progress is to be
      made, the structures of hormone sensitive free-GPI must be elucidated. Only then
      can we precisely define the roles of these molecules in the regulation of cell
      metabolism and proliferation.

PMID- 8274220
TI  - Expression of human bone morphogenetic proteins-2 or -4 in murine mesenchymal
      progenitor C3H10T1/2 cells induces differentiation into distinct mesenchymal cell
      lineages.
AB  - The cDNAs encoding the human bone morphogenetic proteins BMP-2 and BMP-4 in an
      eukaryotic expression vector were permanently transferred into the murine
      mesenchymal progenitor cell line C3H10T1/2. Originally, these cells are known to
      differentiate into myotubes, adipocytes, and chondrocytes upon the addition of
      azacytidine. Permanent transfection of genes encoding human BMP-2 and BMP-4
      induces differentiation into the osteogenic lineage. The osteogenic
      differentiation potential of C3H10T1/2 cells is substantiated by histochemical
      and genetic analyses of marker genes typical or specific for osteogenesis,
      including the parathyroid hormone receptor, alkaline phosphatase, osteopontin,
      osteonectin, and osteocalcin. In addition to osteoblast formation, development
      into adipocytes and chondrocytes is also observed, suggesting that BMP-2 and BMP
      4 induce differentiation into three mesenchymal lineages.

PMID- 8274221
TI  - Cloning and genetic characterization of the human kinesin light-chain (KLC) gene.
AB  - We report the isolation, sequence, and identification of a cDNA encoding the
      human kinesin light-chain (KLC) protein. The cDNA molecule consisted of 276
      nucleotides of 5' untranslated region, the complete coding sequence of 1,710
      nucleotides, and 322 nucleotides of 3' untranslated region. It encoded a
      polypeptide of 569 amino acids and a deduced molecular mass of 64,789 daltons.
      The predicted secondary internal structure of the KLC molecule consisted of about
      27 contiguous repeats, each of approximately 21 amino acid residues, and could be
      divided into three domains. The amino-terminal domain consisted of heptad repeats
      typical of the rod domain of several cytoskeletal proteins. The central and
      carboxy-terminal domains consist of 21-mer repeats. KLC mRNA was expressed in
      most tissues analyzed. The gene, which was expressed in bacteria and Chinese
      hamster ovary cells, was provisionally assigned to the long arm of human
      chromosome 14.

PMID- 8274222
TI  - Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid
      omega-hydroxylase expressed in human kidney.
AB  - A cDNA was isolated from a human kidney lambda gt10 library using the rat CYP4A3
      cDNA as a probe. The cDNA-deduced amino acid sequence encoded a protein of 519
      amino acids that was designated CYP4A11 (Nelson et al., 1993) and exhibited 76%,
      72%, 80%, and 53% similarities to rat CYP4A1, rat CYP4A3, rabbit CYP4A6, and
      human CYP4B1, respectively. The deduced amino-terminal amino acid sequence of
      this cDNA agreed with the amino-terminal amino acid sequence of a major P450
      protein purified from human renal microsomes. A second variant form of CYP4A11
      cDNA, designated CYP4A11v, was isolated from the same library and had a deletion
      of a single adenine residue, thereby extending the reading frame and resulting in
      a protein of 591 amino acids. CYP4A11v is probably encoded by a rare allelic
      variant of CYP4A11, since no mutant alleles were uncovered in 15 normal
      individuals, as determined by a polymerase chain reaction (PCR) diagnostic test.
      Baculovirus-mediated cDNA expression of CYP4A11 yielded a P450 protein having a
      lambda max of 452 nm when reduced and complexed with carbon monoxide. The
      expressed enzyme efficiently catalyzed omega-hydroxylation of lauric acid. No
      detectable activity was uncovered toward arachidonic acid and prostaglandin E1.
      The cDNA-expressed variant, CYP4A11v, was found to be unstable and not to
      efficiently metabolize lauric acid, as assessed by both baculovirus and monkey
      kidney COS cell cDNA expression systems. These studies indicate that CYP4A11 is a
      major fatty acid-metabolizing P450 that is expressed in human kidney.

PMID- 8274223
TI  - Kinesin light chains: identification and characterization of a family of proteins
      from the optic lobe of the squid Loligo pealii.
AB  - Multiple transcripts coding for kinesin light chain isoforms are present in the
      tissues of the squid Loligo pealii. Isoform diversity arises through alternative
      RNA splicing in the amino and carboxyl termini of the putative proteins.
      Comparison to rat and Drosophila proteins demonstrates a remarkable conservation
      of structural domains and regulatory motifs. We have identified a PEST domain
      that may be the site of degradative uncoupling of kinesin functions. Selective
      transcript distribution occurs in disparate tissues, suggesting an adaptation
      toward specialized functions. Expression is highest in the nervous system and
      some evidence for neural-specific transcripts is provided. In neurons, this may
      relate to the differential targeting of specific membrane-bound organelles such
      as synaptic vesicles.

PMID- 8274224
TI  - Unusual gene organization in the protozoan parasite Entamoeba histolytica.
AB  - We have analyzed three independent genomic loci of the protozoan parasite
      Entamoeba histolytica that contain coding regions for the iron-containing
      superoxide dismutase, the pore-forming peptide, and the galactose-inhibitable
      lectin. All of the three structural genes were found to be closely linked
      unidirectionally to other coding sequences. The intergenic regions did not exceed
      1,350 nucleotides. Nuclear run-on data demonstrated that at least the galactose
      inhibitable lectin gene is transcribed in a monocistronic fashion. Comparison of
      the genomic sequences described here with several others reported previously for
      E. histolytica revealed a number of invariable peculiarities for the gene
      organization of this parasite: (i) Coding sequences are not interrupted by
      introns; (ii) 5' untranslated regions are rather short and transcription starts
      at the consensus sequences ATTCA or ATCA; (iii) an unusual TATA-motif is located
      about 30 nucleotides upstream of the start of transcription and comprises the
      sequence TATTTAAA, which reveals protein binding activity as determined by gel
      retardation assays; (iv) the conserved pentanucleotide motif TAA/TTT is found
      within the relatively short 3' untranslated regions and functions putatively as
      the transcription termination signal; and (v) a stretch of up to 12 pyrmidine
      residues is located at the end of transcribed sequences.

PMID- 8274225
TI  - Rapid transcriptional assay for the expression of two distinct reporter genes by
      microinjection.
AB  - We have developed a technique in which gene expression from multiple reporter
      plasmids introduced by needle microinjection can be monitored simultaneously in
      individual cells by double-label indirect immunofluorescence. With constitutively
      active viral promoters, expression from lacZ or chloramphenicol acetyl
      transferase (CAT) reporter genes can be detected within as little as 30 min after
      injection. Expression from such strong promoters reaches a maximum level after
      about 2 hr. In place of the constitutive promoter, promoters containing different
      enhancer elements respond as expected to different stimuli, allowing for the
      comparison of two defined transcriptional control elements in living cells.
      Reporter expression can be analyzed temporally and can be compared to expression
      of endogenous genes. This technique is complementary to transfection and allows
      for the targeted analysis of expression in specific cells, for example, in a
      mixed cell population, and for the analysis of expression in cells that are
      available only in small numbers.

PMID- 8274226
TI  - Analysis of sequence contexts flanking T.G mismatches leads to predictions about
      reactivity of the mismatched T to osmium tetroxide.
AB  - Osmium tetroxide and hydroxylamine are used to detect mutations in DNA and RNA
      after hybridization of mutant and wild-type DNA. Mismatched T and C bases,
      respectively, are modified by these reagents and the DNA strand cleaved at the
      mismatched bases by subsequent treatment with piperidine. This allows detection
      and location of the mutation. Although most T.G mismatches have been reported to
      be reactive to osmium tetroxide, some have been reported to be unreactive. The
      aim of this study was to collect and analyze the reactive and unreactive T.G
      mismatches. We have collected sequence contexts of all reactive and unreactive
      T.G mismatches for analysis. This involves 10 unreactive T.G mismatches (plus one
      T.C) and 19 reactive T.G mismatches. Sequence effects of bases surrounding these
      mismatches must influence this reactivity. There must be many types of such
      sequence effects. We postulate that because of the dominance of 5' G bases near
      the T of unreactive T.G mismatches and the absence of 5' G bases in reactive T.G
      mismatches that the stacking of the 5' G on the mismatched T is the reason for
      this lack of reactivity in the majority of the cases studied here.

PMID- 8274227
TI  - [Prevalence of fascioliasis in humans, horses, pigs, and wild rabbits in 3
      Chilean provinces].
AB  - This study sought to estimate for the first time the prevalence of fascioliasis
      among the rural population in the Chilean provinces of Curico, Talca, and
      Linares, while also determining the disease's prevalence among horses and wild
      rabbits in Curico and Talca and among pigs in Talca. From January 1986 to
      December 1990 a randomly selected sample of 5,861 persons in the three provinces
      was given intradermal, complement-fixation, double-diffusion, and
      immunoelectrophoresis tests to detect antibody to Fasciola hepatica. In addition,
      the ELISA test was used in Talca and Linares. Fecal specimens from horses and
      pigs were inspected for eggs, and the liver and bile ducts of rabbits were
      examined histopathologically. The overall prevalence of infection among the human
      subjects was 0.70%, with rates of 0.6% in Curico, 0.75% in Talca, and 0.71% in
      Linares. The prevalences of infection in horses, rabbits, and pigs were 13.5%,
      6.1%, and 20.6%, respectively. It is estimated that some 2,000 people are
      infected in the study area. It is recommended that rabbits be taken into account
      in all control programs for this zoonosis.

PMID- 8274228
TI  - [The National Program to Control Diarrheic Diseases. Its successes and outlook].

PMID- 8274229
TI  - [The development of a clinical scale for the diagnosis of cholera in infants with
      acute watery diarrhea].
AB  - The diagnosis of cholera in infants based on clinical grounds is often difficult
      because other enteropathogens such as rotavirus or enterotoxigenic Escherichia
      coli (ETEC) can produced a very similar clinical picture. We studied 147 infants
      admitted consecutively to the Rehydration Unit of Cayetano Heredia Hospital in
      Lima, Peru, trying to identified those characteristics significantly associated
      with the isolation of Vibrio cholerae 01 on the admission stool culture. After a
      univariate comparison of cases and controls were selected those characteristics
      that showed a significantly different distribution. These were entered in a
      logistic regression model to analyze their interactions. After this analysis four
      variables remain significantly associated to cases: no history of fever,
      dehydration greater than 7%, fecal pH greater than 7 and no glucose in feces.
      Were developed a diagnostic score with these variables, which had a sensitivity
      of 77.6% and a specificity of 73.6%. It is important to prospectively validate
      the utility of this score.

PMID- 8274230
TI  - [Cholera in children. A report of 8 cases].
AB  - Cholera is an acute intestinal infection caused by Vibrio cholerae 01. When an
      infected person presents severe dehydration and is not adequately treated, he or
      she will develop hypovolemic shock and eventually could died. There is scarce
      information concerning this disease in the Pediatric group. Herein we report on
      eight cases of Pediatric cholera, in children 17 month to four years of age.
      Seven patients out of eight were admitted presenting dehydration. Four presenting
      mild or moderate dehydration and three presenting hypovolemic shock. These three
      patients were rehydrated by intravenous route and thereafter the hydration was
      maintained by oral therapy. The outcome was uneventful in six patients. One
      patient developed abdominal distention probably due to hypopotassemia, and
      another patient presented hyponatremia and seizures. All the patients recovered
      within five days after admission.

PMID- 8274231
TI  - [Oral rehydration therapy: an analysis of its results and impact on the
      hospitalization and mortality of children with diarrhea].
AB  - We present results of four years in oral rehydration therapy (ORT) in the
      Hospital Infantil del Estado de Sonora. There was 10.2 consults by diarrhoea for
      day. Children lower of one year old received oral rehydration therapy in 86.8%,
      were included 11% of prolonged diarrhoea and 32.3% of children with malnutrition.
      During the procedure diarrhoea there was complicated in 3% with paralytic ileus
      sepsis and pneumonia. Effectivity of ORT was in 90.9%; 92.8% in light dehydration
      and 78.7% moderate. Failure in 8.6% was due to vomitus, no acceptation of the
      oral solution, abundant evacuations and other complication presented. Were
      observed reduction in hospitalization, rate of 19.2% in 1986 to 38.4% in 1989.
      The diarrheal mortality decreased in the Urgence Department in 42% and in the
      Infectology Department in 54%. We considered these results as satisfactory, but
      are susceptible to better when we diffuse more the oral rehydration therapy in
      own region.

PMID- 8274232
TI  - [Polydactyly in 26,670 consecutive births. The clinical characteristics,
      prevalence and risk factors].
AB  - OBJECTIVE: The purpose of the study is to determine the prevalence of
      polydactyly, its clinical characteristic and its association with some risk
      factors. MATERIAL AND METHODS: A retrospective, case-control study, of 45 newborn
      with polydactyly and their controls, in 26,670 consecutive births in the Nuevo
      Hospital Civil de Guadalajara, with 20 weeks or more of gestational age, and
      birth weight greater than 500 g, since November of 1988 to October of 1992. The
      information were obtained from the database of the Congenital External
      Malformation Register, carried out by the University of Guadalajara. The
      prevalence of polydactyly was obtained and clinical characteristic were
      documented. Continuous variables were compared using t Student test. For discrete
      variables, analysis were carried out using X2 test and the odds ratio. RESULTS:
      The prevalence of polydactyly was of 1.73 x 1,000 alive newborn. The polydactyly
      of the hands in 26 newborn; preaxial in five and 21 was postaxial. The
      polydactyly in the foot was present in 19 newborn. The only statistics
      differences with control group were: low length and the antecedent of other
      malformation in the family. CONCLUSION: The found prevalence is different to the
      one informed in the literature. The association with antecedent of another
      malformation in the family, support the role of hereditary factors in etiology.

PMID- 8274233
TI  - [The echographic dimensions of the liver in the term newborn and its relation to
      anthropometric variables].
AB  - We decided to undergo a study looking for normal liver size in relation with
      other anthropometric measures. Fifty healthy, appropriate for gestational age
      term-babies, born at the Hospital de Ginecopediatria Numero 48, Centro Medico
      Nacional del IMSS, Leon, Guanajuato, Mexico, were examined by hepatic ultrasound.
      The vertical diameter was 6.0 +/- 0.75 cm, transverse 8.26 +/- 0.72 cm, AP 5.44
      +/- 0.5 cm. The longitudinal cross section area was 16.21 +/- 2.5 cm2, and the
      transverse cross section area 22.53 +/- 3.4 cm2. We found most important
      correlation between vertical diameter and longitudinal cross section area with
      the anthropometric measures. The hepatic measures correlate better with the
      weight. Ultrasound provides a rapid, accurate and convenient method for study the
      liver size and morphology in the neonate.

PMID- 8274234
TI  - [Zygomycosis in childhood. A report of 2 cases].
AB  - Zygomycosis is a fungal infection which shows a definitive predisposition to
      attack the compromised host. It is usually associated with poorly controlled
      diabetes mellitus (DM). In the early infancy the cutaneous and gastrointestinal
      forms are the most frequent, in older children the most recognized form is that
      in which the primary impact of the infection is upon facial and intracranial
      structures. We report two cases of zygomycosis, the first patient was a 15 years
      old girl with a know systemic lupus erythematosus, and the second was a 14 years
      old boy with a insulin-dependent type I DM. Both were treated with anphotericin B
      and aggressive surgical intervention. The favorable outcome was attributed to a
      prompt diagnosis, early initiation of anphotericin B, surgical intervention and a
      control of the underlying illness.

PMID- 8274235
TI  - [Acute postinfectious encephalomyelitis. A case report].
AB  - Acute disseminated encephalomyelitis, an infrequent demyelinating disease,
      complicates some common infections of childhood and is sometimes seen after
      vaccination particularly after rabies vaccination. We describe a six years old
      girl who had an upper respiratory tract infection two weeks prior to death. In a
      retrospective analysis we found that she also had received 14 doses of rabies
      vaccine eight months before her illness. The clinical and pathological features
      of this disease and its relationship with experimental allergic encephalomyelitis
      are analyzed.

PMID- 8274236
TI  - [The split notochord syndrome. A report of 2 cases].
AB  - Split notochord syndrome has been described in several previous case reports;
      however, we recently treated two patients with a previous undescribed variant of
      this syndrome. A 2,800 g male baby was admitted to the neonatal patients room
      with a non covered mass on the lumbo-sacral region, and a portion of intestine,
      with meconium being passed attached to it the legs were equine-varus and the anus
      was absent. Radiographs were consistent with a double spine defect (lumbar and
      sacral split notochord), and the patient was taken to the operating room for
      closure. A 2,600 g male baby was first seen in other hospital, and was admitted
      with a circular defect in the mid-line of the lumbosacral region. This defect was
      conformed by knee, leg, ankle and fingers. Radiographs showed bony structures
      consistent with incomplete lower extremity. During surgery, the skin overlying
      the mass was excised, showing a wide spine defect including stomach, duodenum,
      jejunum, ileum and colon, covered by a peritoneal membrane; there was not
      communication between this structure and the normal digestive tract.

PMID- 8274237
TI  - [Hodgkin's disease with the nephrotic syndrome. A case report].
AB  - It is presented a child with Hodgkin's disease which at diagnosis present
      associated at nephrotic syndrome. Male of nine years old which present a
      ganglionic growing of left jugular chain of one year evolution without systemic
      symptoms and anasarca. Were underwent a ganglionic biopsy with histopathology
      report of Hodgkin's disease mixed cellular variety and renal biopsy with
      histopathology report of minimal change disease. The patient present remission of
      nephrotic syndrome in simultaneous form at the control of the disease. In the
      reported cases of nephrotic syndrome associated with Hodgkin's disease it not
      clear the physiopathology. In this patient were realized immunologic studies of
      renal tissues to treat to find a possible mechanism of action of the neoplastic
      cells on the basal glomerular membrane but we can not found.

PMID- 8274238
TI  - [Asthma: bronchial inflammation and hyperreactivity].
AB  - There is not a clear definition of asthma, actually most of specialist consider
      to asthma how a reversible bronchial obstruction with an increased responsiveness
      (bronchial hyperreactivity, BHR), and inflammation. These inflammation can cause
      increase of the BHR and worseness the process. The new tendencies are to treat
      these BHR and control the two faces of asthma (early and late face). In the early
      or immediate face, bronchodilators are the most use full medicine meanwhile; the
      antiinflammatory drugs (sodium cromoglycate and inhaled steroids) are the best
      option for management of inflammation with reduction of BHR.

PMID- 8274239
TI  - [The system of evaluating the specialty of pediatrics in the Instituto Mexicano
      del Seguro Social].
AB  - A system of evaluation applied to pediatric residents at the Mexican Institute of
      Social Security (IMSS) is presented. Historical precedents; deficiencies and
      modifications of the system are commented. Also institutional system of
      evaluation is described, with emphasis in education strategies: teaching
      attendance-research. Usefulness of knowledge tests, supervision, and assessment
      of evaluation, are mentioned. Finally extrainstitutional evaluation strategies
      are considered.

PMID- 8274240
TI  - Dendritic arborization patterns of cortical interneurons labeled with the lectin,
      Vicia villosa, and injected intracellularly with Lucifer yellow in aldehyde-fixed
      rat slices.
AB  - Neurons whose cell bodies had been stained by a lectin, Vicia villosa, which
      recognizes terminal N-acetylgalactosamine residue, were intracellularly injected
      with Lucifer yellow (LY), in aldehyde-fixed slices of the parietal cortex of
      rats. LY was subsequently visualized immunocytochemically. All injected neurons
      had smooth or only sparsely spiny dendrites and resembled the various forms of
      gamma-aminobutyric acid-ergic neurons previously described in rat neocortex. In
      layers II/III, IV and V, most injected neurons were multipolar. In layer VI, most
      had vertically elongated dendritic fields. Some injected neurons in layer IV had
      an oval or vertically elongated soma and a bitufted dendritic arborization
      pattern. There was a gradual increase in the overall dendritic extent in deeper
      layers of the cortex.

PMID- 8274241
TI  - Autoradiographic localization of [3H]-L-glutamate binding sites in a model of
      cerebellar granule cell ectopia generated by methylazoxymethanol treatment.
AB  - The distribution of [3H]glutamate binding sites was studied in a model of altered
      cerebellar development obtained by injecting methylazoxymethanol (MAM) in 5-day
      old mice. In these mice, at the 25th postnatal day, cerebella were smaller than
      normal, stratification was normal except for the presence in some lobes of a thin
      ectopic granule cell layer in the middle of the molecular layer, the proportion
      of the distribution of [3H]glutamate binding sites between molecular and internal
      granule cell layers was maintained but site density of both quisqualate- and NMDA
      sensitive types was increased in the two layers. In the molecular layer, this
      increase was uniform in spite of the presence of the ectopic cell layer. In the
      internal granular layer, the increase of quisqualate-sensitive and NMDA-sensitive
      [3H]glutamate binding sites is topographically segregated and the first
      corresponds to areas of lesser cellular density. These results show that MAM
      treatment induces persistent alterations of the cerebellar glutamatergic system,
      which consist of receptor over-expression, possibly due to deficit of
      innervation, reactive gliosis and immaturity of surviving granule cells.

PMID- 8274242
TI  - Tumor necrosis factor as a mediator of shock, cachexia and inflammation.
AB  - Tumor necrosis factor is a cytokine made by macrophages, monocytes and T cells
      that has been formed to play an important role in shock, cachexia and
      inflammation. The importance of this cytokine eliciting shock and cachexia in
      mammals is reviewed.

PMID- 8274243
TI  - Blocking interleukin-1 in disease.
AB  - Numerous studies implicate a role for cytokines in the pathogenesis of disease.
      These are primarily derived from experiments in which cytokines are injected into
      experimental animals and disease activity is monitored. Other studies measure
      elevated cytokines in either animals or humans during the development of disease.
      Although cytokines are thought to play a role in the outcome of various diseases,
      only a few have been directly implicated as mediators of the pathogenic
      mechanisms of illness and death of the host. Recent studies using specific
      cytokine antagonism have shed considerable light on which cytokines appear to be
      playing a critical role.

PMID- 8274244
TI  - Interleukin-1, TNF alpha and their naturally occurring antagonists in sepsis.
AB  - Recent evidence has demonstrated that specific inhibitors of the proinflammatory
      cytokines, IL-1 and TNF alpha, circulate in the blood of healthy individuals and
      concentrations of these inhibitors are elevated in inflammation. Initial
      characterization reveals that one of the classes of IL-1 inhibitors that
      circulates is the newly described IL-1 receptor antagonist (IL-1ra). A class of
      newly described TNF inhibitors is the soluble type I (p55) and type II (p75) TNF
      receptor (sTNFR). In patients with nonlethal infections, both IL-1ra and sTNFR
      appear to circulate at levels that can block the quantities of IL-1 and TNF alpha
      produced. However, such concentrations of inhibitors are inadequate to prevent
      the deleterious host responses to exaggerated proinflammatory concentrations seen
      in lethal septic shock. Nevertheless, administering either IL-1ra or soluble TNF
      receptors to raise plasma concentrations 1,000-fold can prevent the pathologic
      sequelae associated with excessive cytokine production.

PMID- 8274245
TI  - Dialysis-induced hypotension: a fresh look at pathophysiology.

PMID- 8274246
TI  - Drug clearance by continuous haemodiafiltration. Analysis of sieving coefficients
      and mass transfer coefficients of diffusion.
AB  - In patients who were treated with continuous arteriovenous haemodiafiltration
      (CAVHD), using the AN-69 capillary dialyser, we measured the clearance rates of
      uraemic solutes and drugs at dialysate flow rates of 0, 1 and 3 l/h. By using a
      mathematical model of CAVHD, we analysed the data in terms of sieving
      coefficients and diffusive mass transfer coefficients. These parameters proved to
      be related to drug protein binding and molecular weight. The parameter values may
      be used to calculate the expected drug clearance rate under different operating
      conditions.

PMID- 8274247
TI  - Pathologic quiz case 2. Oncocytic schneiderian papilloma.

PMID- 8274248
TI  - Pathologic quiz case 1. Wegener's granulomatosis.

PMID- 8274249
TI  - Reconstructive surgery papers presented at the Academy's fall meeting.

PMID- 8274250
TI  - Preoperative thyroid scanning in presumed thyroglossal duct cysts.

PMID- 8274251
TI  - Sinus neoplasia.
AB  - After an overview of the epidemiology, histology, and evaluation of nasal and
      sinus neoplasms, this article discusses surgical advances in facial
      translocation, skull base dissection, and defect reconstruction. With the
      aforementioned, the question of what is technically resectable vs what is curable
      has become an important but as yet unanswered question. Radiation therapy,
      combined with surgery or as palliation, presents special challenges in the head
      and neck, and ports must be carefully defined to minimize damage to vision and
      adjacent cranial structures. Chemotherapy is usually reserved for palliation,
      though some report favorable results with induction treatment of squamous cell
      carcinomas with platin-based regimens.

PMID- 8274252
TI  - A new bilobed design for the sensate radial forearm flap to preserve tongue
      mobility following significant glossectomy.
AB  - OBJECTIVE: A new bilobed design of the sensate radial forearm flap is presented
      for reconstruction of the oral cavity following significant glossectomy. One lobe
      of the flap is used to restore the shape and volume of the tongue, while the
      second lobe is used to resurface the floor of the mouth and the gingiva. SETTING:
      Tertiary referral center. PATIENTS: Ten patients who underwent significant
      glossectomy for squamous cell cancer were included in this study. Patients were
      deemed candidates for this form of reconstruction when at least one half of the
      mobile tongue was resected and the residual tongue had an intact motor nerve
      supply. RESULTS: In addition to the thin, pliable, and sensate tissue of the
      radial forearm skin, the bilobed design helps to prevent tethering of the root of
      the tongue to the inner table of the mandible. This factor is felt to be
      important in maximizing the mobility of the residual tongue. There were no flap
      failures or partial necroses. Tongue mobility, oral alimentation, articulation,
      and return of sensation are described.

PMID- 8274253
TI  - The platysma myocutaneous flap. Indications and caveats.
AB  - The platysma myocutaneous flap has enjoyed limited popularity despite its
      versatility, dependability, and ease of harvesting. In this article, we describe
      12 consecutive patients who underwent platysma flap reconstruction of various
      oral cavity and oropharyngeal defects. Complications included loss of one skin
      paddle, one pharyngocutaneous fistula, and one intraoral wound dehiscence. In all
      patients, bare bone was covered or appropriate spacing between the tongue and
      other structures was maintained to avoid ankyloglossia. We discuss specific
      indications and caveats.

PMID- 8274254
TI  - Vascularized bone flaps in oromandibular reconstruction. A comparative anatomic
      study of bone stock from various donor sites to assess suitability for enosseous
      dental implants.
AB  - OBJECTIVE: To identify donor sites from which vascularized bone may be harvested
      capable of accepting osseointegrated implants of the minimum dimensions required
      to ensure long-term implant stability. DESIGN: An anatomic study of the most
      commonly employed donor sites for vascularized bone in oromandibular
      reconstruction was conducted on 28 cadavers. SETTING: Academic tertiary referral
      center. PARTICIPANTS: Twenty-eight freshly embalmed, adult white cadavers (16
      male, 12 female) were dissected. INTERVENTION: The ipsilateral fibula, iliac
      crest, radius, and lateral border of the scapula were harvested and multiply
      sectioned at predetermined sites. OUTCOME MEASURE: Implantability was determined
      for each section based on measurements of height, width, and cross-sectional area
      utilizing computer planimetry. RESULTS: The iliac crest was the most consistently
      implantable donor site, followed by the scapula, fibula, and radius (83%, 78%,
      67%, and 21% of sections from each donor site satisfying the criteria for
      implantability). Consistent regional differences in implantability were
      encountered at each donor site except the scapula. CONCLUSIONS: Following
      ablation of oromandibular malignant neoplasms, restoration of stable retentive
      dentition is a prerequisite to a successful functional oral rehabilitation. This
      is best achieved with enosseous implants, capable of supporting a stable dental
      prosthesis, placed directly into vascularized bone flaps at the time of
      mandibular reconstruction. The implications of the results obtained in this study
      for gender, donor site selection, and orientation of the vascularized bone flap
      are discussed.

PMID- 8274255
TI  - Management of mandibular fractures.
AB  - The complex physiology of the masticatory system is extremely sensitive to its
      intricate anatomic relationships. With the ever-increasing number of patients
      admitted to our institution with traumatic facial injuries, it seemed an
      appropriate time to evaluate the most widely employed treatment modalities
      available for the management of mandibular fractures. Maxillomandibular fixation
      remains the mainstay of mandible fracture stabilization. Within recent years,
      rigid internal fixation with miniplates and screws has become popular. This study
      compares the results of the most commonly used treatment modalities available for
      the repair of acute mandibular fractures.

PMID- 8274256
TI  - Bone graft implantation for correction of the anophthalmic orbit.
AB  - Prosthetic rehabilitation of the anophthalmic orbit may result in a syndrome
      characterized by retrodisplacement and tilt of the prosthesis, deepening of the
      upper eyelid sulcus, retraction of the upper eyelid, and stretching of the lower
      eyelid. Patients requiring enucleation of the orbit following trauma can also
      have accentuation of the enophthalmos, with hypophthalmos and displacement of the
      malar eminence. These cosmetic defect are difficult to manage, and a number of
      corrective surgical techniques have been described. In this study we review the
      pathophysiology of the anophthalmic orbit and present our recent experience
      utilizing the strategic placement of iliac crest bone grafts to compensate for
      the bony and soft-tissue injuries associated with traumatic loss of the globe.
      All six patients experienced subjective and objective improvement
      postoperatively. Results are presented as case presentations with accompanying
      photographs and follow-up data.

PMID- 8274257
TI  - Pharmacologic enhancement of random skin flap survival by prostaglandin E2.
AB  - This study evaluated the effect of prostaglandin E2 on skin flap survival in the
      porcine model. Dorsal random skin flaps on hypopigmented 15- to 25-kg pigs were
      used. Prostaglandin E2 (10 ng/kg per minute) was infused for 2 days prior to
      surgery and continued during the 7-day postoperative period. Mean flap survival
      was 52.58% +/- 3.62% for the control group and 68.51% +/- 3.34% for the
      experimental group (P < .05). A moderate correlation existed between
      prostaglandin E2 serum levels and flap viability. A strong correlation was noted
      between red blood cell flexibility and the amount of flap survival (r = .86). As
      red blood cell flexibility increased, the survival percentage also increased.
      Although prostaglandin E2 reduced adenosine diphosphate-induced platelet
      aggregation from a baseline of 86.08% +/- 8.33% to 54.61% +/- 17.21%, no
      correlation was noted between the amount of platelet aggregation and percent flap
      survival (r = .52).

PMID- 8274258
TI  - Long-term pretreatment with pentoxifylline increases random skin flap survival.
AB  - Optimizing survival of random skin flaps is essential to ensure successful
      rehabilitation of patients in whom flap reconstruction is necessary. This study
      tested the hypothesis that pentoxifylline improves random skin flap survival in
      porcine dorsal flank flaps when administered for at least 2 weeks preoperatively.
      Specific aims included establishing the mechanisms by which pentoxifylline
      enhanced survival. Treatment with pentoxifylline (25 mg/kg per day) for 14 days
      before surgery and for 7 days thereafter significantly increased mean flap
      survival to 73.2% +/- 4.5% compared with mean flap survival of 49.6% +/- 2.2% in
      untreated pigs. Increased flap survival was associated with a parallel increase
      in red blood cell flexibility. Plasma concentration of pentoxifylline ranged from
      92.9 to 122.7 ng/mL but did not correlate directly with the improved flap
      survival. Likewise, pentoxifylline decreased platelet aggregation; there was a
      trend toward increased flap survival in those pigs with the least amount of
      aggregation. Thus, pentoxifylline improves random flap survival but only after a
      sufficient pretreatment period of at least 14 days.

PMID- 8274259
TI  - The effects of the inhalational anesthetic agent combination, isoflurane-nitrous
      oxide, on survival in a pig random skin flap model.
AB  - Using a dorsally based, random skin flap model in 14 swine, the influence on skin
      flap survival of isoflurane used with nitrous oxide as maintenance anesthetic
      agents was examined. The mean area of skin flap survival was 54.9% for the
      experimental group compared with 28.6% in the control group. Arterial blood gas
      content (PO2, PCO2, and HCO3-), respiratory rate, acid-base balance, blood
      pressure level, pulse rate, and temperature were monitored. Improved survival of
      the isoflurane-nitrous oxide group was independent of these parameters. These
      data support the findings of a previous study that isoflurane positively affects
      random skin flap survival in a swine model. Furthermore, the addition of nitrous
      oxide partially reduces isoflurane's beneficial effects.

PMID- 8274260
TI  - Clinical results of percutaneous implants in the temporal bone.
AB  - The bone-anchored hearing aid is an alternative to the conventional bone
      conduction hearing aid, without the disadvantages of pressure pain or skin
      irritation and with direct sound transmission to the skull. The bone-anchored
      hearing aid is coupled to a percutaneous titanium implant, which is placed in the
      mastoid process in two surgical stages. We analyzed the clinical results of 68
      percutaneous implants in 65 patients. After a follow-up period of 8 to 45 months,
      97% of the implants were anchored in the bone. In 86% of the implants, no
      potentially dangerous skin reactions occurred. The occurrence of skin reactions
      was not time dependent. Movement of the skin, thick skin, and poor skin condition
      around the implant were related to the onset of skin reactions. This study showed
      that the percutaneous titanium implant forms a stable link between the bone
      anchored hearing aid and the skull.

PMID- 8274261
TI  - Cisplatin, fluorouracil, and leucovorin. Increased toxicity without improved
      response in squamous cell head and neck cancer.
AB  - OBJECTIVE: To evaluate the activity and toxicity of the drug combination
      cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin
      calcium (PFL) as induction chemotherapy in patients with advanced and untreated
      squamous cell head and neck (SCHN) cancer. DESIGN: Nonrandomized, prospective
      trial. SETTING: Referral center (comprehensive cancer center). PATIENTS: Twenty
      two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx
      (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment
      would have required total laryngectomy. INTERVENTIONS: Three cycles of PFL were
      administered prior to local-regional therapy (concomitant cisplatin and radiation
      and/or neck dissection, with total laryngectomy reserved for nonresponse or
      relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short
      intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous
      infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL
      combination was administered every 21 days. MAIN OUTCOME MEASURES: Clinical
      response to chemotherapy and observed toxic effects during chemotherapy. RESULTS:
      Five patients were inevaluable for response, with three early deaths (infection
      in two and sudden death in one), one cerebrovascular accident, and one patient
      declining further chemotherapy. Of the remaining 17 patients, 10 had a major
      response to chemotherapy, but in only five patients (29%) was this complete (95%
      confidence interval, 8% to 51%). Other significant toxic effects included grade 3
      to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10. CONCLUSIONS:
      While PFL is active in patients with SCHN cancer, we were unable to reproduce the
      high complete response rates reported by other centers. Its use can be associated
      with significant toxic effects. We do not recommend the use of PFL for the
      treatment of patients with SCHN cancer outside the context of a clinical trial
      until there is further critical assessment of its activity and toxicity.

PMID- 8274262
TI  - A prospective study of ingested foreign bodies in Singapore.
AB  - OBJECTIVE: To evaluate the following: the symptoms, physical signs,
      investigation, and treatment of impacted foreign bodies (FBs); the dimensions of
      FBs according to site of impaction; and epidemiology, risk factors, and
      complications of FB ingestion. DESIGN: Prospective analysis of 397 patients with
      a history of FB ingestion. SETTING: Department of Otolaryngology, Tan Tock Seng
      Hospital, Singapore, a referral center with institutional practice. PATIENTS: Of
      the 397 patients treated between May and December 1991, ingested FBs were found
      in 197 patients. INTERVENTION: Foreign bodies were removed with forceps under
      direct or indirect vision; if this was impossible, removal was done
      endoscopically. RESULTS: Dysphagia, positive laryngeal rub, and drinking water
      tests had high sensitivity and specificity for esophageal FBs. Large and rigid
      FBs of various shapes tend to lodge in piriform fossae and esophagus and might
      cause complications if not removed early. The risk factors of FB ingestion were
      use of dentures and Chinese method of cooking and eating. The complication rate
      of impacted FBs was 5.1% and increased with the delay in seeking treatment.
      Flexible esophagoscope was found to be as effective as rigid esophagoscope in
      retrieving esophageal FBs. Lesions simulating impacted FBs were found in nine
      patients. In 162 patients in whom no FB was found, the symptoms resolved
      spontaneously within 16 days. CONCLUSION: Dysphagia, positive laryngeal rub, and
      drinking water tests are indicative of impacted FBs that must be removed early to
      prevent complications. Ability to use both rigid and flexible esophagoscopes is
      advantageous in FB retrieval.

PMID- 8274263
TI  - Inhibition of alpha-adrenergic responses in the rat liver by lipophilic K+
      channel blockers or depolarizing Cl- gradients. Evidence for a potential
      sensitive step in the signal transduction path.
AB  - To study the role of K+ channels and membrane potential in alpha-adrenergic
      responses of the rat liver, lipophilic K+ channel blockers quinidine and 4
      aminopyridine were used or external Cl- was replaced with gluconate, an
      impermeant ion. Glucose release, O2 uptake, portal pressure, and K+ flux were
      measured in the isolated perfused liver. The alpha-agonist phenylephrine caused
      biphasic changes in each parameter, a fast transient followed by sustained
      elevated responses. Infusion of 5 mM 4-aminopyridine, 0.1 mM quinidine, or
      gluconate prior to phenylephrine inhibited each parameter, with the greatest
      inhibition occurring during the second phase. A similar pattern was seen with 2
      mM EGTA. This contrasts with the full inhibition of all responses following
      exposure to the alpha-antagonist phentolamine. Infusion of each inhibitor at the
      peak of the sustained phase inhibited all responses. Phenylephrine-stimulated
      release of K+ was augmented in the presence of EGTA and was inhibited by 4
      aminopyridine or quinidine. In contrast, beta-adrenergic stimulation of glucose
      release and K+ flux were not affected by the K+ channel blockers. Phenylephrine
      stimulated glucose release from hepatocyte suspensions decreased by about 50% in
      the presence of 4-aminopyridine, EGTA, or gluconate. The results are discussed in
      terms of a potential role for K+ channels in alpha-adrenergic signal transduction
      in the liver.

PMID- 8274264
TI  - Synthesis and characterization of a fragment of an ice nucleation protein.
AB  - Synthetic peptides were used as models for studying the conformation of ice
      nucleation proteins. We chemically synthesized four peptides (16-, 24-, 32-, and
      48-mer) that consisted of two to six repeats of the consensus repeating
      octapeptide unit of ice nucleation proteins and evaluated their conformation by
      circular dichroism spectroscopy. These model peptides exist predominantly as
      random coils in aqueous solution, but adopt alpha-helical structures in the
      presence of trifluoroethanol. The stability of their secondary structures was
      investigated by monitoring the pH and time dependence of their circular dichroism
      spectra. Our results indicated that the alpha-helical content of the 48-mer
      exhibited a significant pH dependence, while that of the 24- and 32-mer peptides
      did not. The 32-mer was the only peptide that transformed from the alpha-helical
      to a beta-sheet structure upon storage. We suggest that the overall conformation
      of the ice nucleation protein could be a beta-sheet.

PMID- 8274265
TI  - Ontogeny of hepatocyte proliferation inhibitor activity during human liver
      development and its effect on cell proliferation in in vivo and in vitro studies.
AB  - Ontogeny of hepatocyte proliferation inhibitory (HPI) activity was studied during
      human liver development. HPI activity was first noticed in the cytosolic fraction
      of 20-week-old fetal liver and thereafter it began to increase with the liver
      maturation. An inverse correlation between the ontogeny of HPI activity and
      mitotic counting of the hepatocytes during human liver development was
      established. The crude HPI fraction from fetal and adult human liver inhibited
      the incorporation of [3H]thymidine into the DNA of 2-day-old rat liver and HepG2
      cells and the inhibitory effect was directly proportional to the age of the HPI
      source. Prolonged exposure of HepG2 cells to the HPI fraction was also found to
      be cytotoxic. Preliminary characterization of the crude HPI fraction revealed an
      age-dependent increase in proteins of 18, 28, and 60 kilodaltons following silver
      chloride staining of sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      and densitometric scanning.

PMID- 8274266
TI  - Substrate- and effector-induced conformational changes in phosphofructokinase
      from white muscle of rainbow trout (Oncorhynchus mykiss): a fluorescence study.
AB  - Results of activity and spectral studies using fluorescence show that AMP and
      fructose 2,6-bisphosphate (F2,6P2) activate muscle phosphofructokinase (PFK) from
      rainbow trout (Oncorhynchus mykiss) through specific and similar conformational
      changes. Inorganic compounds, such as ammonium and phosphate ions, also increase
      enzyme activity allosterically; however, the structural alterations in the enzyme
      caused by these effectors are quite different from those caused by AMP and
      F2,6P2. No effects of the inorganic compounds on the environment of tryptophan
      residues of the enzyme were observed. Mg-ATP, a substrate of the enzyme, acts as
      an allosteric inhibitor at high concentrations. Although Mg-ATP and citrate
      inhibit the enzyme activity in a synergistic way, the conformational effects of
      these negative effectors are different. Mg-ATP caused a drastic decrease in
      fluorescence intensity of the enzyme, whereas citrate did not.

PMID- 8274267
TI  - Expression of the protooncogene c-jun is maintained during myogenic
      differentiation in rat L6 myoblasts.
AB  - Skeletal myoblasts undergo terminal differentiation when maintained under low
      mitogen conditions. We have examined the expression of c-jun, one of the growth
      factor-inducible immediate-early genes, during myogenic differentiation of L6
      myoblasts. The steady-state levels of c-jun mRNA, c-Jun polypeptide, and
      activator protein 1 binding activity were not markedly altered in L6 cells
      undergoing myogenic differentiation. Although expression of c-jun is induced by
      serum mitogens in fibroblasts and other cell lines, addition of high serum to
      proliferating myoblasts resulted in the activation of another immediate early
      gene junB, but not c-jun mRNA expression. These results indicate that regulation
      of c-jun may differ from that of other immediate early genes in L6 cells.
      Manipulation of myogenesis by exposing L6 cells to dimethyl sulfoxide also
      suggested that expression of myogenin and muscle differentiation could occur in
      the presence of high levels of c-Jun. Furthermore, expression of c-jun from
      Moloney murine leukaemia viral long-terminal repeat in transfected L6 cells
      confirmed that constitutive expression of c-jun does not interfere with
      myogenesis in L6 myoblasts. Therefore, regulation of c-jun expression in rat L6
      cells differs from that in the mouse C2 cell line.

PMID- 8274268
TI  - Nucleosides and glutamine are primary energy substrates for embryonic and adult
      chicken red cells.
AB  - It has been assumed that glucose is a major energy yielding substrate for chicken
      red blood cells. In this report we show that glucose fails to maintain cellular
      ATP levels in embryonic and mature chicken erythrocytes during overnight
      incubation. Of over a dozen metabolites tested, inosine, guanosine, and glutamine
      were the most efficacious ATP-sustaining substrates. Of seven potential citric
      acid cycle substrates, only glutamine significantly sustained ATP levels.
      Incubation with inosine plus glutamine sustained the ATP level at over 70% of the
      initial value found in embryonic chicken red cells. Uridine, cytidine,
      xanthosine, glutamate, and pyruvate were ineffective substrates. Similar results
      were obtained with adult erythrocytes, except that glutamine plus inosine fully
      sustained ATP levels during long-term incubation. Adenosine did not sustain ATP
      levels. Below 1 mM, the adenosine level was rapidly exhausted and above 1 mM its
      presence led to cell lysis. The ability of some nucleosides to maintain ATP
      levels is consistent with the high numbers of nitrobenzylthioinosine binding
      sites (nucleoside transporter sites) both in mature chicken red cells
      (approximately 10,000 sites/cell) and in embryonic red cells (approximately
      30,000 sites/cell). Unlike pig red cells which switch from glucose to nucleosides
      at the erythrocyte stage, chicken cells show primary dependence on nucleoside
      metabolism at the embryonic stage.

PMID- 8274269
TI  - Equine ovarian aromatase: evidence for a species specificity.
AB  - Mare granulosa cells and cyclic corpus luteum microsomes are reported to
      aromatize 19-norandrogens more efficiently than androgens. However, 16 alpha
      hydroxytestosterone and epitestosterone were not aromatized by the equine corpus
      luteum microsomal estrogen synthetase. These results indicate that the equine
      aromatase system would be different from the human placental microsomal estrogen
      synthetase, which aromatizes 16 alpha-hydroxyandrogens and epitestosterone but
      not 19-norandrogens. Furthermore, our data show that the rates of aromatization
      of androgens and 19-norandrogens were not additive and that 19-norandrogens
      competitively inhibited the aromatization of androgens, suggesting that a single
      enzymic system would be involved in the aromatization of androstenedione, 19
      norandrostenedione, testosterone, and 19-nortestosterone. Our findings, which are
      identical to those previously reported for stallion testis and mare placental
      estrogen synthetases, provide evidence for a strong species specificity of the
      equine aromatase system.

PMID- 8274270
TI  - In vitro growth-stimulatory property of pigeon milk.
AB  - Five cell lines were employed to test the growth-stimulating property of pigeon
      milk in vitro. All the cell lines except A431 showed good growth response to
      crude homogenates of pigeon milk. Enhancement of DNA synthesis in quiescent
      Chinese hamster ovary (CHO) cells by pigeon milk was dose dependent up to a
      concentration of 1%. In vitro growth stimulation by 1% pigeon milk was
      approximately equal to that by 2% foetal bovine serum (FBS) when CHO cells were
      used, growth stimulation of Vero cells by 1% pigeon milk was roughly three times
      of that by 2% FBS. In contrast, 1% pigeon milk was only half as active as 2% FBS
      on NIH/3T3 cells and five times less active than 2% FBS on human foetal lung
      fibroblast cells. After dialysis using a relative mass (M(r)) cutoff of 3500, the
      pigeon milk mitogenic activity was retained in the dialyzed solution, although it
      decreased by 40-60% when dialyzed with M(r) cutoffs of 8000 and 12,000-14,000.
      The growth-stimulating activity of pigeon milk was resistant to heat, acid,
      alkali, and the action of urea, guanidine hydrochloride, dithiothreitol, and
      trypsin. We suggest that pigeon milk is a new source of growth factor(s) capable
      of stimulating in vitro the growth of many mammalian cell types.

PMID- 8274271
TI  - Purification and molecular properties of glycogen phosphorylase b from trout
      white muscle.
AB  - Glycogen phosphorylase b (EC 2.4.1.1) was isolated from white skeletal muscle of
      rainbow trout (Oncorhynchus mykiss) and purified 214-fold to a final specific
      activity of 135 U/mg protein (assayed in the direction of glycogen breakdown at
      21 degrees C) by using glycogen--concanavalin A, DEAE-Sephadex, and 3',5'-cAMP
      affinity chromatography. Purified phosphorylase b was a dimer with a native
      molecular weight of 193,000 and a subunit molecular weight of 87,000. Michaelis
      constants for glycogen, phosphate, and AMP were 128 microM, 31 mM and 142 microM,
      respectively, at pH 7.2; maximum activity of the enzyme was obtained at pH 7.5
      and 25 degrees C. Glucose and ATP behaved as phosphorylase b inhibitors; glucose
      inhibition decreased at lower pH values. IMP did not affect the enzyme. The
      catalytic properties of trout phosphorylase b indicate that the enzyme would be
      virtually inactive at the physiological concentration of substrates and
      activators found in resting trout white muscle, but changes in cellular pH, ATP,
      Pi, and AMP levels during burst muscle work could allow phosphorylase b to
      augment phosphorylase a activity and make a substantial contribution to overall
      glycogenolysis in working trout white muscle.

PMID- 8274272
TI  - Single calcium channels and acetylcholine release at a presynaptic nerve
      terminal.
AB  - The relationship between calcium influx and the gating of transmitter release was
      examined at the release face of a cholinergic presynaptic nerve terminal using a
      technique that allows the simultaneous recording of both calcium channels at the
      single-channel level and quantal acetylcholine secretion. Acetylcholine release
      occurred during large inward calcium currents through many simultaneously open
      channels but was also gated by very small calcium transients, admitting less than
      200 ions, when only one channel was open at a time. These findings provide
      functional support for a highly structured model of the transmitter release face
      in which the synaptic vesicle release mechanism is closely tethered to one or
      more presynaptic calcium channels and the opening of only one of these may be
      sufficient to trigger quantal secretion.

PMID- 8274273
TI  - Molecular localization of regions in the L-type calcium channel critical for
      dihydropyridine action.
AB  - Sensitivity to dihydropyridines (DHPs) is a distinct characteristic that
      differentiates L-type Ca2+ channels from T-, N-, and P-type Ca2+ channels. To
      identify regions necessary for the functional effects of DHPs, chimeric Ca2+
      channels were constructed in which portions of motif III or motif IV of a DHP
      insensitive brain Ca2+ channel, BI-2, were introduced into the DHP-sensitive
      cardiac L-type Ca2+ channel. The resultant chimeric Ca2+ channels were expressed
      in Xenopus oocytes, and the effects of a DHP agonist and antagonist were studied.
      The results show that the linker region between S5 and S6 in motif IV of the L
      type Ca2+ channel is a major site for DHP action. The DHP agonist and antagonist
      molecules interact with distinct sites on the alpha 1 subunit of the L-type Ca2+
      channel. The data further show that the SS2-S6 region of motif III is not
      involved in DHP action but may be an important structural component of
      inactivation.

PMID- 8274274
TI  - PKA mediates the effects of monoamine transmitters on the K+ current underlying
      the slow spike frequency adaptation in hippocampal neurons.
AB  - The Ca(2+)-activated K+ current IAHP, which underlies spike frequency adaptation
      in cortical pyramidal cells, can be modulated by multiple transmitters and
      probably contributes to state control of the forebrain by ascending monoaminergic
      fibers. Here, we show that the modulation of this current by norepinephrine,
      serotonin, and histamine is mediated by protein kinase A in hippocampal CA1
      neurons. Two specific protein kinase A inhibitors, Rp-cAMPS and Walsh peptide,
      suppressed the effects of these transmitters on IAHP and spike frequency
      adaptation. The effects of the cyclic AMP analog 8CPT-cAMP were also inhibited,
      whereas muscarinic and metabotropic glutamate receptor agonists had full effect.
      Intracellular application of protein kinase A catalytic subunit or a phosphatase
      inhibitor mimicked the effects of monoamines or 8CPT-cAMP. These results
      demonstrate that monoaminergic modulation of neuronal excitability in the
      mammalian CNS is mediated by protein phosphorylation.

PMID- 8274275
TI  - A heart-like Na+ current in the medial entorhinal cortex.
AB  - Acutely dissociated neurons from the superficial layers of the medial entorhinal
      cortex of the rat were studied under voltage clamp using the whole-cell patch
      clamp configuration. Neurons from the medial entorhinal cortex exhibit a
      tetrodotoxin (TTX)-resistant Na+ current (ITTX-R; IC50 approximately 146 nM), in
      addition to the normal TTX-sensitive Na+ current (ITTX-S; IC50 approximately 6
      nM). ITTX-R was found in both putative stellate and putative pyramidal neurons
      from the medial entorhinal cortex. ITTX-R is kinetically indistinguishable from
      ITTX-S, but can be distinguished from ITTX-S based on its enhanced sensitivity to
      block by Cd2+, La3+, and Zn2+. ITTX-R is kinetically and pharmacologically
      similar to the TTX-resistant Na+ current found in cardiac muscle.

PMID- 8274276
TI  - Assembly of the inhibitory glycine receptor: identification of amino acid
      sequence motifs governing subunit stoichiometry.
AB  - The inhibitory glycine receptor (GlyR) is a pentameric protein composed of two
      types (alpha and beta) of membrane-spanning subunits. Coexpression in Xenopus
      oocytes of a low affinity mutant of the alpha 2 subunit with the alpha 1 and beta
      subunits indicated that GlyRs assembled from alpha 1 and alpha 2 polypeptides
      contain variable subunit ratios, whereas alpha/beta hetero-oligomers have an
      invariant (3:2) stoichiometry. Analysis of different alpha/beta chimeric
      constructs revealed that this difference in assembly behavior is mediated by the
      N-terminal extracellular regions of the receptor subunits. Substitution of
      residues diverging between the alpha and beta subunits identified combinations of
      sequence motifs determining subunit stoichiometry.

PMID- 8274277
TI  - Heterogeneity in presynaptic regulation of GABA release from hippocampal
      inhibitory neurons.
AB  - Release of GABA from the terminals of hippocampal inhibitory neurons is inhibited
      by activation of GABAB autoreceptors and mu opioid receptors. However, it is not
      known whether these presynaptic processes affect all inhibitory synapses equally.
      We examined the effects of the GABAB receptor agonist baclofen and the mu opioid
      receptor agonist DAGO on postsynaptic currents evoked by minimal stimulation of
      inhibitory fibers (meIPSCs) in area CA3. Baclofen reversibly depressed
      approximately half of the meIPSCs evoked in the stratum pyramidale. The remaining
      meIPSCs were unaffected despite a coincident depression of spontaneous IPSCs. In
      contrast, all meIPSCs were depressed by DAGO. In addition, minimal stimulation in
      the stratum radiatum evoked meIPSCs that were always depressed by baclofen. These
      results indicate that regulation of GABA release by GABAB autoreceptors occurs at
      a subset of inhibitory synapses and that GABAB-resistant inhibitory synapses are
      located on pyramidal neuron somata. Hippocampal inhibitory neurons may be
      heterogeneous with respect to presynaptic receptor-mediated regulation of GABA
      release.

PMID- 8274278
TI  - Induction of axonal growth by heterophilic interactions between the cell surface
      recognition proteins F11 and Nr-CAM/Bravo.
AB  - F11 and Nr-CAM/Bravo are two axon-associated glycoproteins belonging to different
      subgroups of the immunoglobulin superfamily. In this report we have investigated
      the interaction of both proteins using neurite outgrowth and binding assays.
      Antibody blocking experiments demonstrate that neurite extension of tectal cells
      on immobilized F11 is mediated by Nr-CAM/Bravo. Binding studies further reveal a
      direct heterophilic interaction between F11 and Nr-CAM/Bravo. This activity can
      be mapped to the amino-terminal second or third immunoglobulin-like domain within
      F11 with domain-specific monoclonal antibodies and deletion mutant proteins
      expressed on COS cells. Furthermore, perturbation experiments with domain
      specific monoclonal antibodies demonstrate that this region is required for
      adhesion and neurite extension.

PMID- 8274279
TI  - Cytokine-induced programmed death of cultured sympathetic neurons.
AB  - Programmed cell death (PCD) of sympathetic neurons is inhibited by nerve growth
      factor. However, factors that induce PCD of these cells are unknown. Leukemia
      inhibitory factor (LIF) and ciliary neurotrophic factor, neuropoietic cytokines
      known to regulate sympathetic neuron gene expression, were examined for effects
      on survival of cultured sympathetic neurons. Treatment with LIF or ciliary
      neurotrophic factor caused neuronal death in a dose-dependent fashion. Inhibition
      of RNA or protein synthesis, or treatment with potassium, all of which prevent
      PCD after nerve growth factor deprivation, prevented LIF-induced death. The
      morphologic and ultrastructural characteristics of the neuronal death induced by
      LIF and by nerve growth factor deprivation were similar. Furthermore, LIF
      treatment resulted in DNA fragmentation with a characteristic "ladder" on
      Southern blot analysis. These observations suggest that neuron numbers may be
      regulated by factors which initiate PCD, as well as by factors which prevent it.

PMID- 8274280
TI  - Delayed formation of the floor plate after ablation of the avian notochord.
AB  - We have examined the long-term effects of notochord ablation at chick stages 9-10
      on formation of the floor plate and motor neurons. Although missing or reduced 2
      days postablation, the floor plate and motor neurons were morphologically normal
      by 4 postoperative days. When isolated whole or ventral, but not lateral, neural
      plate fragments from stage 9 embryos were cultured for 4 days in collagen gels,
      floor plate and neural markers were observed. Our results suggest that floor
      plate and motor neurons can form in a delayed fashion in vivo after notochord
      ablation and in vitro from isolated neural plates. This suggests that either
      there is an early induction of floor plate by the chordamesoderm of Hensen's
      node, or only limited interactions between the neural plate and notochord
      immediately after neurulation are required for floor plate determination.

PMID- 8274281
TI  - Genetic deletion of a neural cell adhesion molecule variant (N-CAM-180) produces
      distinct defects in the central nervous system.
AB  - N-CAM is abundantly expressed in the nervous system in the form of numerous
      structural variants with characteristic distribution patterns and functional
      properties. N-CAM-180, the variant having the largest cytoplasmic domain, is
      expressed by all neurons. The N-CAM-180-specific exon 18 has been deleted to
      generate homozygous mice unable to express this N-CAM form. The most conspicuous
      mutant phenotype was in the olfactory bulb, where granule cells were both reduced
      in number and disorganized. In addition, precursors of these cells were found to
      be accumulated at their origin in the subependymal zone at the lateral ventricle.
      Analysis of the mutant in this region suggests that the mutant phenotype involves
      a defect in cell migration, possibly through specific loss of the polysialylated
      form of N-CAM-180, which is expressed in the migration pathway. Subtle but
      distinct abnormalities also were observed in other regions of the brain.

PMID- 8274282
TI  - Identification of a seven transmembrane helix receptor for corticotropin
      releasing factor and sauvagine in mammalian brain.
AB  - We have identified and characterized cDNAs encoding a novel receptor that is a
      member of a distinct class of seven transmembrane helix, Gs-coupled receptors.
      This receptor mediates ligand-dependent stimulation of intracellular cAMP levels
      in response to physiologic concentrations of corticotropin-releasing factor (CRF)
      and to the related frog skin peptide, sauvagine. The pattern of CRF receptor mRNA
      expression in the brain, pituitary gland, and other organs corresponds precisely
      to that predicted for the classic CRF receptor, suggesting that this receptor
      serves to mediate the known biological effects of CRF on behavior, stress, and
      homeostasis. Alternative splicing events generate a second, relatively abundant
      gene product expressed in a distinct ontogenic pattern. These findings serve to
      identify the receptor for an important neuropeptide.

PMID- 8274283
TI  - A CNS-specific POU transcription factor, Brn-2, is required for establishing
      mammalian neural cell lineages.
AB  - The pluripotent embryonal carcinoma cell line P19 can differentiate in vitro into
      neurons and astrocytes. By employing this neural cell differentiation system, we
      have studied the expression and function of a POU transcription factor implicated
      in mammalian neurogenesis. When P19 cells differentiated to the neural cells, one
      of the CNS-specific POU genes (Brn-2) was selectively induced. The induction of
      Brn-2 was specific to the neural cell lineages and took place at the early stage
      of differentiation. When the Brn-2 induction was blocked/delayed by antisense
      RNA, such cells were unable to differentiate to neurons and astrocytes. Instead
      they differentiated to nonneural cells, including smooth and skeletal muscle
      cells. Furthermore, with reduced levels of antisense RNA, differentiation to
      neural cells occurred. These results indicate that Brn-2 is essential for the
      neural cell differentiation of P19 cells and suggest that Brn-2 is one of the
      genes required for establishing neural cell lineages in mammals.

PMID- 8274284
TI  - Drug addiction: a model for the molecular basis of neural plasticity.

PMID- 8274285
TI  - Interleukin-8 production from cultured human dermal fibroblasts by stimulation
      with supernatant of cultured human epidermal cells.
AB  - There is much evidence to support the theory that keratinocytes and dermal
      fibroblasts actively participate in inflammatory reactions by the production of
      proinflammatory mediators or cytokines. We investigated the neutrophil
      chemotactic activity in conditioned media of cultured epidermal cells and dermal
      fibroblasts, and found that an epidermal cell-derived factor induced fibroblasts
      to produce a neutrophil chemotactic factor. This neutrophil chemotactic factor
      was identified as interleukin-8 (IL-8) by the elution position on HPLC and by a
      neutralization test that uses monoclonal anti-IL-8 antibody (14E4). The epidermal
      cell-derived factor was fractionated together with thymocyte-proliferating
      activity on Sephadex G-75 gel chromatography followed by HPLC. It was blocked
      specifically by anti-interleukin-1 (IL-1) alpha antibody, which indicates that
      this factor was IL-1 alpha. Since a variety of inflammatory dermatoses is
      characterized by the infiltration of neutrophils into the skin, induction of IL-8
      production in fibroblasts by epidermal cells may play an important role in
      inflammatory skin diseases.

PMID- 8274286
TI  - Potassium channel openers stimulate DNA synthesis in mouse epidermal keratinocyte
      and whole hair follicle cultures.
AB  - We have conducted studies using primary mouse epidermal keratinocyte and whole
      hair follicle cultures to investigate the mechanism of the hypertrichotic
      activity of potassium channel openers. In a time course study, the extent of
      stimulation of epidermal keratinocyte DNA synthesis by minoxidil increased as the
      rate of DNA synthesis in control cultures declined. Minoxidil stimulation of DNA
      synthesis in 7-day cultures required prolonged (> 1 day) exposure to the agent.
      Pinacidil and diazoxide also stimulated DNA synthesis in mouse epidermal
      keratinocyte cultures. In addition, minoxidil, pinacidil, diazoxide, and
      cromakalim stimulated DNA synthesis in whole-organ cultures of mouse hair
      follicles. These results suggest that potassium channel openers retard the loss
      of proliferative activity of differentiating keratinocytes and support the
      hypothesis that these agents stimulate hair growth through a direct effect on
      hair follicles.

PMID- 8274287
TI  - Studies on the pharmacokinetics and metabolism of prednicarbate after cutaneous
      and oral administration.
AB  - Prednicarbate (PC) is a nonhalogenated derivative of prednisolone which is used
      for the local treatment of corticoid-sensitive skin diseases. In this study, the
      pharmacokinetics and the metabolism of PC in humans are investigated after
      cutaneous ointment application (75 mg PC) and after systemic oral administration
      (40 mg PC) in 8 healthy volunteers. In addition, the possible suppression of
      endogenous cortisol secretion by both application forms was monitored. After oral
      administration no intact PC, but significant levels of the first metabolite
      prednisolone-17-ethylcarbonate (PRED-17-EC) were determined. PRED-17-EC was
      further metabolized with a half life of 1.6 h to prednisolone. After percutaneous
      administration neither PC nor other known metabolites could be detected
      systemically. The low systemic bioavailability after dermal application was also
      reflected in an unchanged cortisol secretion pattern. According to animal studies
      our metabolic studies in humans suggest that the prednisolone-17-ester PRED-17
      EC, which has a receptor binding affinity comparable to that of dexamethasone is
      the pharmacologically active compound. As PRED-17-EC subsequently undergoes an
      inactivation step to the low active prednisolone this may be the reason for the
      dissociation of good local efficacy and low systemic side effects.

PMID- 8274288
TI  - Comparison of the bioactivity of mometasone furoate 0.1% fatty cream,
      betamethasone dipropionate 0.05% cream and betamethasone valerate 0.1% cream in
      humans. Inhibition of UV-B-induced inflammation monitored by laser Doppler blood
      flowmetry.
AB  - The bioactivity of a novel topical glucocorticosteroid, mometasone furoate 0.1%
      fatty cream was compared with betamethasone dipropionate 0.05% cream and
      betametasone valerate 0.1% cream. An ultraviolet light (UV-B)-induced
      inflammation assay in humans was used, and the combined effect of a single, open
      application of the corticosteroids was evaluated. Reduction of UV-B induced
      inflammation was monitored by laser Doppler blood flowmetry, clinical skin
      scoring and skin reflectance spectrophotometry. Skin scoring and reflectance
      spectrophotometry were found unsuitable because one of the cream vehicles
      contained titanium dioxide which shielded skin erythema. Laser Doppler blood
      flowmetry showed that mometasone furoate 0.1% fatty cream was more than twofold
      better in reducing UV-B-induced inflammation than betamethasone dipropionate
      0.05% cream and betametasone valerate 0.1% cream, and that the effect was
      sustained for at least 24 h after a single application.

PMID- 8274289
TI  - Effects of sphingosine, isoquinoline and tannic acid on the human tape-stripping
      model and the psoriatic lesion.
AB  - Published data (mainly from rodent skin) suggest a correlation between compounds
      which inhibit protein kinase C (PKC), have anti-inflammatory or antitumor
      characteristics and possess antipsoriatic potential. We have investigated the
      effects of topical application of sphingosine (a naturally occurring PKC
      inhibitor), isoquinoline (a component of coal tar which showed antipsoriatic
      capacities in the mouse tail model) and tannic acid (a plant phenol with
      antitumor activity) on human skin. In each case we have assessed (a) the level of
      induction of ornithine decarboxylase (ODC) following Sellotape stripping as an
      indicator for potential PKC inhibition in vivo, and (b) its effects on the
      lesions of chronic plaque psoriasis. The control group consisted of 18 healthy
      volunteers, used for the ODC induction experiments (0.0/0.1/0.2 M sphingosine in
      ethanol, 100% coal tar and 0/50 mM tannic acid in acetone) and 17 psoriatic
      patients used for double-blind scoring of two randomly selected lesions (0.0/0.1
      M sphingosine in ethanol, 0.0/0.2% isoquinoline in white vaseline/lanette wax
      cream 50%/50% and 0/10% tannic acid in lanette wax cream) and also for some of
      the ODC induction experiments (0.0/0.2% isoquinoline and 0/10% tannic acid).
      Biopsies were taken 8 h after stripping and ODC activity was assessed by
      measurement of 14CO2 release. Lesions were scored with a modified psoriasis area
      and severity index on days 0, 7 (isoquinoline and tannic acid), 13 (sphingosine)
      and 21 (isoquinoline and tannic acid). Application of 0.1 or 0.2 M sphingosine
      resulted in a decrease of ODC activity of 52% and 66%, respectively (p < 0.01),
      but histologic sections showed intraepidermal necrosis.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8274290
TI  - In vivo evaluation of the stratum corneum barrier function in blacks, Caucasians
      and Asians with two noninvasive methods.
AB  - This study compared in man the in vivo barrier function of stratum corneum in
      three racial groups: black, Caucasian and Asian, by two noninvasive technics.
      They were transepidermal water loss (TEWL) determination measured with an
      evaporimeter and laser Doppler velocimetry (LDV) to measure the lag time before
      the vasodilation induced by application of methyl nicotinate (10 microliters of
      0.5% solution in ethanol/propylene glycol 95/5 v/v). Both methods were performed
      simultaneously on each forearm of 7 black, 8 caucasian and 6 Asian subjects
      before and after removal of the stratum corneum by stripping. TEWL measurements
      were higher (p < 0.01) in Asians and Blacks compared to Caucasians. Stripping (8
      or 12 strips) increased TEWL in all groups; TEWL increase percentage was higher
      (p < 0.05) in Asians compared to Caucasians. Vasodilatation lag times assessed by
      LDV showed that skin permeability was more important in Asians (p < 0.01) and in
      Caucasians (p < 0.05) than in blacks. Lag times decreased with stripping. After 8
      or 12 strips, the order of sensitivity was: Asian > Caucasian > black. Our study
      showed that, with both noninvasive methods, removal of the stratum corneum
      increased permeability, with racial differences.

PMID- 8274291
TI  - Comparative study of the activity and lingering effect of topical antifungals.
AB  - We present a combined method of culturing pathogenic dermatophytes and yeasts on
      human stratum corneum. Topical marketed antifungals are applied in vivo, and the
      stratum corneum is removed by cyanoacrylate skin surface strippings. After
      inoculation of the test organism, the extent of fungal growth is measured,
      indicating by comparison with controls the level of inhibitory effect of the
      antifungal. Other samples of stratum corneum collected at different time
      intervals after the arrest of antimicrobial treatment are used to evaluate the
      lingering effect of the drug. The combination of the data gained by these
      approaches close to the in vivo situation is used to introduce a classification
      of antifungals.

PMID- 8274292
TI  - Influence of ageing on the in vivo mechanics of the skin.
AB  - The response of the skin to common in vivo tests (in-plane uniaxial stretch,
      torsion, indentation and levarometry) is analyzed in terms of their suitability
      for ageing studies. The analysis suggests that low-load indentation and small
      deformation levarometry are well suited for ageing studies since the skin
      response under these tests can be directly related to its structure and
      constituent properties (known to be affected by ageing). The measured forehead
      skin response under these tests in 'young' (20-26 years) and 'old' (64-80 years)
      subjects is presented and compared with predictions of corresponding models. The
      results show that levarometry is more sensitive to ageing than indentometry.

PMID- 8274293
TI  - Effects of the Avene spring water on the dynamics of lipids in the membranes of
      cultured fibroblasts.
AB  - In this preliminary report, dealing with the biological properties of Avene
      spring water, we investigated its effects on membrane properties of cultured
      human skin fibroblasts used as a model cell system. It is shown that incubation
      of these cells in the presence of Avene spring water brings about an increase in
      the fluidity of plasma membrane. This effect was evidenced by a decrease in the
      fluorescence anisotropy of the lipophilic probe diphenylhexatriene and by a 3
      fold increase in the lateral diffusion coefficient of the lipophilic probe 5-(N
      hexadecanoyl)-aminofluorescein, as measured through fluorescence recovery after
      photobleaching experiments. This effect reached a maximum for incubation times
      longer than 30 min and for a dilution of Avene water in laboratory water to about
      20-25%. As discussed, changes in the hydrodynamic properties of cell membranes
      induced by Avene water provide a plausible explanation for some of the biological
      events this spring water is known to trigger.

PMID- 8274294
TI  - Selection and characterization of a variant of human melanoma cell line, A375
      resistant to growth inhibitory effects of oncostatin M (OM): coresistant to
      interleukin 6 (IL-6).
AB  - Human melanoma cell line A375 is extremely sensitive to growth inhibitory effects
      of oncostatin M (OM). A375 cells resistant to the antiproliferative effect of OM
      were isolated by exposing OM-sensitive cells to ethyl methane sulfonate (EMS) for
      24 h followed by continuous exposure to OM. An A375 subline resistant to OM
      induced growth inhibition was selected by a limiting dilution technique and
      designated 4-1.10". The resistant cells were completely refractory to OM even up
      to a concentration of 500 ng/ml. Interestingly, the resistant cells were also
      nonresponsive to the growth inhibitory effects of interleukin-6 (IL-6). Other
      cytokines such as transforming growth factor beta (TGF-beta), interleukin-1 (IL
      1), and tumor necrosis factor alpha and beta (TNF-alpha and TNF-beta) exhibited
      similar growth inhibitory effects on OM-sensitive or -resistant cells. OM
      resistant cells were found to possess approximately 20% of OM receptors with the
      same affinities as compared to the parental OM-sensitive cells. However, the
      affinities and number of receptors for IL-6 were the same on both cell types. The
      OM treatment did not alter the cyclic AMP (cAMP) level of either the parental or
      the resistant cells. The OM-resistant cell line will be very useful in
      elucidating the mechanism of OM-elicited growth inhibition.

PMID- 8274295
TI  - Prevention of the hematopoietic toxicity associated with zidovudine in vivo with
      IL-1 alone or in combination with GM-CSF administered to normal mice.
AB  - We studied the effect of interleukin-1 (IL-1 alpha) either alone or administered
      with GM-CSF on the induction of hematopoietic toxicity associated with zidovudine
      (AZT) in vivo, as determined by peripheral blood indices, and assays of
      hematopoietic progenitors, i.e., erythroid (BFU-E), myeloid (CFU-GM), and
      megakaryocyte (CFU-Meg) cultured from bone marrow and spleen. Previous results
      reported from this laboratory have established dose-escalation of zidovudine to
      normal mice induced a dose-dependent decrease in hematocrit, WBC, and platelets
      with altered populations of marrow and splenic erythroid, myeloid and
      megakaryocyte progenitors. Daily administration of IL-1 alpha (recombinant
      murine, 5 u/animal) with or without GM-CSF (recombinant murine (10
      micrograms/kg/bw) was associated with reduced AZT-toxicity as measured by
      increases in peripheral blood indices and progenitor stem cells, i.e., CFU-GM,
      CFU-Meg and BFU-E cultured from either bone marrow and spleen. The presence of GM
      CSF amplified the effect observed with IL-1 especially with respect to
      myelopoiesis. These results demonstrate IL-1 with or without GM-CSF reverses AZT
      hematopoietic toxicity when used in vivo.

PMID- 8274296
TI  - Transforming growth factor-beta accelerates osteoinduction in a craniofacial
      onlay model.
AB  - Recombinant human transforming growth factor beta 1 was added to a demineralized
      bone matrix (DBM) paste, formed into cylinders and implanted onto the cranial
      periosteum of New Zealand White rabbits. The TGF-beta was added at doses of 0,
      0.3, 3, 30 and 75 micrograms per implant. When the implants were removed after
      six weeks, histomorphometric analysis of the implants showed that TGF-beta
      induced significantly higher levels of trabecular bone formation than in the
      controls (mineralized bone area 6.0 +/- 0.8, 6.0 +/- 1.2, 5.6 +/- 1.0, 10.1 +/-
      1.5, and 10.8 +/- 1.4 mm2, respectively, P < 0.05), TGF-beta also caused greater
      resorption of the demineralized bone matrix carrier (matrix area 7.2 +/- 0.9, 6.8
      +/- 1.4, 3.7 +/- 0.9, 2.7 +/- 1.2, 0.9 +/- 0.5 mm2, respectively, P < 0.02).
      Measurements of the osteoid demonstrated a more active bone surface and there was
      evidence of rapid bone remodeling. Similar results were obtained using TGF-5
      beta, a new hybrid molecule. These results demonstrate the capacity of
      transforming growth factor beta in accelerating osteoinduction.

PMID- 8274297
TI  - Cell density regulates differential production of bFGF transcripts.
AB  - In vitro cultures of human retinal pigment epithelial (RPE) cells were used to
      study the regulation of basic fibroblast growth factor (bFGF) gene expression.
      Four transcripts of 7.0, 3.7, 2.2, and 1.2 kB are produced from the bFGF gene.
      Increasing cell density has a profound effect on the expression of the 7.0 kB
      transcript relative to the 3.7 kB transcript. Here, evidence is presented
      suggesting that posttranscriptional processing events are responsible for
      differential expression of the 7.0 and 3.7 kB bFGF transcripts as a function of
      cell density. Primer extension analysis demonstrates that these two transcripts
      originate from a single transcription initiation site. Determination of the half
      lives of the 7.0 and 3.7 kB transcripts at confluent cell density did not explain
      the relative expression of these mRNAs. These differences may arise from the use
      of alternative polyadenylation sites in the 3' untranslated region (UTR) as a
      function of cell density. Polysomal analysis indicates no selective translation
      of any of the four bFGF transcripts in RPE cells.

PMID- 8274299
TI  - Secretion of epidermal growth factor-like molecular species by lung parenchymal
      macrophages: induction by interferon-gamma.
AB  - A population of cells enriched for pulmonary interstitial macrophages was
      obtained by differential adherence of lung parenchymal cells released by
      dissociation with trypsin. These cells secreted a molecule or molecules that
      bound to epidermal growth factor (EGF) receptors expressed on pulmonary
      fibroblasts. Secretion was reproducibly stimulated by exposure of the macrophages
      to interferon-gamma. Binding to EGF receptors could be blocked by a polyclonal
      antibody to EGF. It could also be partially blocked by incubation with heparin,
      suggesting that at least a component of the activity might be due to a member of
      the heparin-binding subgroup of the EGF family of growth factors. Because
      pulmonary fibrosis is consistently associated with inflammatory accumulation of
      activated T-lymphocytes, induction by interferon-gamma of growth factor secretion
      by macrophages could have pathogenetic importance. We speculate that similar
      cellular interactions may play a role in the progression of other chronic
      inflammatory lesions to fibrosis.

PMID- 8274298
TI  - Multiple transcription start sites in the rat insulin-like growth factor-I gene
      give rise to IGF-I mRNAs that encode different IGF-I precursors and are processed
      differently in vitro.
AB  - Two distinct class 1 and class 2 rat liver IGF-I mRNAs contain different 5'
      leader exons, 1 and 2. RNase protection, primer extension, RACE PCR and
      ribonuclease H mapping established the complete structure of the 5' end of class
      1 and class 2 IGF-I mRNAs. Two major transcription start sites in exon 1 yield
      class 1 IGF-I mRNAs, including 345 or 245 bases of exon 1. Multiple, clustered
      transcription start sites in exon 2 yield class 2 IGF-I mRNAs with 84-50 bases of
      exon 2. Cell-free translation of in vitro transcribed IGF-I mRNAs suggests that
      class 1 and class 2 mRNAs preferentially initiate translation at distinct AUG
      codons to result in IGF-I precursors with either 48 residue class 1 pre-peptides
      or 32 residue class 2 pre-peptides. Some translation initiation also occurs at a
      downstream AUG common to class 1 and 2 mRNAs to yield IGF-I precursors with a 22
      residue pre-peptide. Inclusion of microsomal membranes in translations suggests
      that the three different pre-peptides each function as co-translationally cleaved
      signal peptides. However, treatment of processed precursors with endoglycosidase
      H indicates that co-translational processing of precursors with 22 and 32 residue
      pre-peptides leads to glycosylation of downstream IGF-I precursor sequences
      whereas co-translational processing of precursors with 48 residue pre-peptide is
      not associated with glycosylation.

PMID- 8274300
TI  - Constitutive and inducible expression of PDGF in the human basophilic cell line,
      KU 812.
AB  - The human basophilic cell line KU 812, that also has some mast cell
      characteristics, was found to express the PDGF-A gene and secrete PDGF-A like
      activity. After treatment with IL-6+ TNF-alpha, the PDGF-A mRNA expression
      increased as did cytoplasmic immunostaining with anti-PDGF antibodies. Secretion
      of PDGF-A was visualized by immunoprecipitation. An augmentation of non-secreted
      PDGF-like activity after IL-6+ TNF-alpha treatment was not accompanied by
      induction of the long splice variant of the PDGF-A-chain mRNA. Treatment with TPA
      caused an increase in PDGF-A expression and in addition, an induction of PDGF-B
      transcripts were seen. Staining of cytospin preparations with anti-PDGF
      antibodies visualized a substantial increase in immunostaining of the TPA treated
      cells and both intracellular and secreted PDGF-AA-like activity was substantially
      increased as compared to untreated control cultures. There was a concomitant
      induction of exon 6 specific mRNA, corresponding to a cellular retention signal
      after TPA treatment. Our results show that PDGF can be produced by a cell line of
      the basophilic/mast cell lineage, i.e. cells involved in allergic disorders and
      inflammation.

PMID- 8274301
TI  - European Guidelines for Quality Assurance in Cervical Cancer Screening. Europe
      against cancer programme.

PMID- 8274302
TI  - Basic biomechanical measurements of bone: a tutorial.
AB  - Although bone densitometry is often used as a surrogate to evaluate bone
      fragility, direct biomechanical testing of bone undoubtedly provides more
      information about mechanical integrity. Like any other specialized field,
      biomechanics contains its own techniques and vocabulary. This article serves as a
      guide to biomechanical principles and testing techniques for bone specimens.

PMID- 8274303
TI  - Nongenomic regulation of chondrocyte membrane fluidity by 1,25-(OH)2D3 and 24,25
      (OH)2D3 is dependent on cell maturation.
AB  - 1,25-(OH)2D3 and 24,25-(OH)2D3 regulate rat costochondral chondrocyte cultures in
      a metabolite-specific manner; 1,25-(OH)2D3 targets primarily growth zone cells
      (GC) and 24,25-(OH)2D3 targets primarily resting zone cells (RC). Some of the
      effects are nongenomic, since incubation of isolated membrane fractions with the
      metabolites results in regulation of enzyme activities comparable to that seen in
      culture. This study examined whether changes in membrane fluidity might be one
      mechanism involved in the nongenomic regulatory pathway. Chondrocyte cultures
      were incubated with the vitamin D metabolites and changes in plasma membrane
      fluidity monitored using the fluorophore, TMA-DPH, which is specific for
      membranes exposed to external fluids. Isolated matrix vesicles were also
      incubated directly with the metabolites and anisotropy of the membrane, as well
      as alkaline phosphatase-specific activity, determined. 1,25-(OH)2D3 caused a
      rapid and constant increase in alkaline phosphatase-specific activity in GC
      matrix vesicles; 24,25-(OH)2D3 caused an increase in RC matrix vesicle enzyme
      activity that was both dose- and time-dependent. Matrix vesicles produced by GC
      had a lower degree of fluidity than their parent plasma membranes or RC plasma
      membranes and matrix vesicles. Fluidity of the GC membrane fractions was
      increased by 1,25-(OH)2D3 in a dose- and time-dependent manner. 1,25-(OH)2D3 had
      no effect on the fluidity of the RC membranes. 24,25-(OH)2D3 caused a decrease in
      fluidity in GC at later time points. This metabolite caused an increase in
      fluidity of RC plasma membranes that returned to normal levels by 6 h; however,
      the increase induced in the matrix vesicles remained elevated throughout the 24-h
      experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274304
TI  - 3-Amino-1-hydroxypropylidine-1-bisphosphonate (AHPrBP) suppresses not only the
      induction of new, but also the persistence of existing bone-forming surfaces in
      rat cancellous bone.
AB  - Although bone formation is coupled to resorption in both man and the rat, it is
      not known whether similar mechanisms are involved in these two species. To
      investigate this, we have attempted to further characterise the suppression of
      bone formation by the potent bone resorption inhibitor 3-amino-1
      hydroxypropylidine-1-bisphosphonate (AHPrBP) in ovariectomised adult female rats.
      To see whether AHPrBP affects the activity of preexisting bone forming surfaces,
      as opposed to preventing the induction of new forming surfaces, three consecutive
      fluorochrome labels were administered 3, 10, and 17 days prior to sacrifice. The
      percentage of trabecular surface covered by first and second labels only
      (arrested surface), second and third labels only (induction surface), and all
      three labels (persisting surface) were recorded at the secondary spongiosa of the
      proximal tibial metaphysis. As expected, ovariectomy increased the proportion of
      induction surfaces, with AHPrBP preventing this increase. However, AHPrBP also
      reduced the proportion of persisting surfaces, implying inhibition of the
      activity of preexisting bone-forming surfaces. We conclude that resorption
      inhibitors such as AHPrBP inhibit bone formation in the rat in a manner which
      appears inconsistent with the site-specific coupling seen in the adult human
      skeleton.

PMID- 8274305
TI  - Recovery from disuse osteopenia coincident to restoration of muscle strength in
      mdx mice.
AB  - The objective of this study was to compare the tibial structure and the strength
      of the tibia during muscle weakness and after recovery in mdx mice (which
      demonstrate X-linked muscular dystrophy and subsequent muscle regeneration) and
      age-matched control mice. The extent of disuse atrophy produced by muscle
      weakness and recovery following restoration of normal muscle strength could then
      be determined. The tibiae adjacent to weakened tibialis anterior muscles of 4
      week-old mdx mice had significantly reduced radiographic density (p < 0.05) and
      cortical thickness (p < 0.001), and increased porosity (p < 0.001) compared to
      age-matched controls, suggesting development of disuse osteopenia. Significantly
      less force was required to break mdx tibiae than age-matched control tibiae (p <
      0.05). In addition, Sharpey's fiber density was reduced (p < 0.001), suggesting a
      weakened attachment of the tibialis anterior muscle to bone. At 12 weeks, during
      the period of muscle regeneration, mdx tibial cortical thickness (p < 0.001) and
      porosity (p < 0.01) remained significantly lower, but percent calcium and
      Sharpey's fiber and radiographic densities were significantly greater (p < 0.001)
      than in age-matched controls, suggesting that bone mineralization and muscle
      attachment strength had increased to above normal levels in parallel with
      recovery of strength by the attached muscle. By 18 weeks, mdx tibial cross
      sectional area, cortical thickness, and porosity remained significantly less (p <
      0.001) than normal. Although Sharpey's fiber density was greater than in age
      matched controls (p < 0.001) by 18 weeks, mdx tibial percent calcium (p < 0.005)
      and Sharpey's fiber density (p < 0.001) were significantly reduced from levels in
      12-week-old mdx animals. There was significantly less deformation of the tibia
      prior to fracture in mdx than control tibiae at 18 weeks of age, suggesting
      tibial brittleness. Thus, at the site of attachment of mdx muscle to osteopenic
      bone, the remodelling which accompanies recovery of muscle strength is atypical,
      and produces an attachment of greater strength than function appears to require.
      These observations suggest that data are needed regarding bone mass and muscle
      bone attachments in humans with disuse osteopenia, DMD, and other neuromuscular
      diseases.

PMID- 8274306
TI  - Mechanobiologic influences in long bone cross-sectional growth.
AB  - We developed a computer model to simulate the interaction of biological and
      mechanobiological factors in the development of the cross-sectional morphology of
      long bones. The model incorporated a strong influence of biologically induced
      bone formation during early development. In addition, an assumed mechanical
      loading history during growth and development corresponding to age-related
      changes in body weight and muscle mass was applied. Based on the bone stress
      stimulus generated by the assumed loads, mechanically induced apposition and
      resorption rates were calculated at the periosteal and endosteal surfaces using a
      previously developed bone modeling theory. These methods successfully emulated
      the growth-related changes seen in long bone diaphyseal structure as well as
      changes observed in mature bones during aging. The simulations recreated the
      rapid increase in bone dimensions during development, stabilizing at maturity,
      and then the gradual, age-related subperiosteal expansion and cortical thinning.
      Throughout the growth, development, and aging simulations, the values of the bone
      radii, area, moments of inertia, and apposition rates corresponded well with
      measurements documented by other researchers.

PMID- 8274307
TI  - Secular increase and geographical differences in hip fracture incidence in
      Norway.
AB  - In 1988 and 1989, 2790 hip fractures were reported from the urban population of
      Oslo (annual incidence per 10,000 in the age group 50 years and older: women
      118.7, men 45.4). For the same period, 385 fractures were reported from the rural
      population of the county Sogn og Fjordane (annual incidence per 10,000 in the age
      group 50 years and older: women 74.6, men 36.7). The hip fracture incidence in
      Oslo had increased for all sex and age groups above 50 years (except women 50-59
      years) in the 10-year period 1978/79 to 1988/89. The incidence of hip fractures
      in Sogn og Fjordane was only 65% of the incidence in Oslo. These results support
      previous reports on a secular increase and geographical differences in hip
      fracture incidence.

PMID- 8274308
TI  - Adaptations of immature trabecular bone to moderate exercise: geometrical,
      biochemical, and biomechanical correlates.
AB  - Strenuous endurance exercise can adversely affect the mechanical integrity of
      immature bone, but it is unclear whether a more moderate exercise regimen would
      have a positive effect. Thus, to investigate the response of immature trabecular
      bone to moderate exercise, we randomly assigned female Sprague-Dawley rats (8
      weeks old) to either a basal-control, exercise, or age-matched control group. The
      basal-control rats were killed at 8 weeks of age, while the other two groups were
      killed at 18 weeks of age. Between 8 and 18 weeks, one group remained sedentary,
      while another group was trained progressively on a motor-driven treadmill at a
      moderate level of intensity. Rat femoral necks (FN) were tested in cantilever
      bending to failure, and the sixth lumbar vertebral bodies (L6) were compressed to
      50% of their initial height. Both tissues were analyzed for calcium,
      hydroxyproline, and collagen-crosslinking concentrations, and for changes in
      geometry. The adrenal mass per unit body mass was significantly greater in the
      exercised group, compared to the age-matched controls. L6 calcium content,
      compressional stress, and elastic modulus were significantly less in the exercise
      group as compared to the age-matched control group. Nonreducible collagen
      crosslinks (hydroxylysylpyridinoline [HP] and lysylpyridinoline [LP]) were
      significantly greater in the older exercise and age-matched control L6 and FN. In
      the weightbearing FN--but not L6--the LP concentration of the exercise group was
      significantly greater than the age-matched controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8274309
TI  - Systematic assessment of bone resorption, collagen synthesis, and calcification
      in chick embryonic calvaria in vitro: effects of prostaglandin E2.
AB  - A systematic method has been developed to assess bone resorption, matrix
      formation, and calcification in a single calvarial culture from 20-day-old chick
      embryos. The bones were prelabeled with 45Ca by an injection into the egg white
      before culture. In the last 2 h of incubation, the bones were further labeled
      with both 3H-proline and 3H-tetracycline. Bone resorption was assessed as 45Ca
      release into the medium. Collagen synthesis was measured by the incorporation of
      3H-proline into collagenase-digestible protein (CDP). Since tetracycline has been
      commonly used as an in vivo marker for osteoid calcification, we assessed in
      vitro calcification as the uptake of 3H-tetracycline into bone. By using this
      method, we studied the effects of prostaglandin E2 (PGE2) and indomethacin, which
      inhibits biosynthesis of PGE2, on bone resorption and formation. The cultured
      bone synthesized approximately 300 ng of PGE2 during every 24 h of incubation,
      and indomethacin (10(-6) M) completely inhibited the synthesis. In indomethacin
      treated cultures, % 45Ca release and the labeling of CDP were significantly
      reduced. These reductions were not seen when exogenous PGE2 (10(-9) M) comparable
      to its endogenous level was added along with the indomethacin. Furthermore, 10(
      8) to 10(-5) M PGE2 increased % 45Ca release and the CDP labeling. In addition,
      the uptake of 3H-tetracycline into the cultured bone was also enhanced by PGE2.
      In devitalized calvaria, PGE2 had no effect on 3H-tetracycline uptake, suggesting
      that the stimulative effect on PGE2 was cell-mediated.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8274310
TI  - The culture of human osteoblasts upon bone graft substitutes.
AB  - In order to assess the ability of six potential bone graft substitutes to support
      the growth of human osteoblasts, these cells were grown in culture and then
      plated onto fragments of the six materials and cultured for a further period of
      15 days. Tests to confirm the osteoblastic phenotype of the cells included
      spectrophotometric alkaline phosphatase assay; Western blotting of secreted
      osteocalcin, osteonectin, bone sialoprotein, and collagen type I; and
      mineralization within the cultures provided with a supplemented medium. Cells
      were seeded onto the materials in 24-well plates (Nunc, Naperville, IL) at
      density levels 12,500 cells/cm2 and 25,000 cells/cm2. Specimens were examined
      after the 15-day culture period by scanning electron microscopy. At a seeding
      density of 12,500 cells/cm2 results showed that the human osteoblasts had
      greatest affinities for demineralized rat bone and demineralized Surgibone,
      whilst few osteoblasts were found attached to Pyrost, Surgibone, or coral. The
      collagen matrix of Callopat hydrated in the culture media exposing the
      hydroxyapatite crystals within it, and these became the foci for cell attachment
      and growth. At a seeding density of 25,000 cells/cm2 the osteoblasts had attached
      to and proliferated upon the surfaces of all the materials, forming multilayers,
      with the exception of Surgibone. These experiments demonstrated that all the
      materials, with the exception of nondemineralized Surgibone, were biocompatible
      for human osteoblasts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274311
TI  - Estimation of vertebral body strength by dual photon absorptiometry in elderly
      individuals: comparison between measurements of total vertebral and vertebral
      body bone mineral.
AB  - The aim of the present study was to investigate the predictive value of bone
      mineral measurements by dual photon absorptiometry (DPA) in vitro for strength
      and ash weight of lumbar vertebral bodies in elderly, otherwise nonselected
      individuals. The material comprised 46 individuals: 26 males (43-95 years) and 20
      females (63-95 years) without malignant diseases. Spinal segments, including L2,
      L3, and L4, were removed en bloc at autopsy. Bone mineral content (BMC)
      measurements imitating the normal DPA procedure were performed on the segments
      suspended in a water bath. The segments were measured in toto (BMCT) and
      remeasured after removal of the posterior elements (BMCB). The second lumbar
      vertebral body (L2) was then dissected and sawed below the endplates to obtain
      samples with planoparallel ends before compression in a materials testing
      machine. Finally, the bone specimens were incinerated for ash weight estimations.
      BMCT showed significant correlations to vertebral body ash weight (r = 0.79),
      compressive strength (load, r = 0.69), and stress (load per unit area, r = 0.47).
      The correlations were improved by removing the posterior elements (BMCB-ash
      weight, r = 0.86, BMCB-load, r = 0.74, BMCB-stress, r = 0.49). Correction of BMC
      for differences in vertebral body height (BMC/cm) further increased the
      correlation coefficients (BMCB/cm-ash weight, r = 0.92, BMCB/cm-load, r = 0.78,
      BMCB/cm-stress, r = 0.55). We conclude that lumbar BMC is predictive for lumbar
      vertebral body compressive strength in vitro and ash weight. The correlation
      coefficient is improved by removing the posterior non-weight-bearing
      element.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274312
TI  - The skeletal effects of colony-stimulating factor-1 in toothless (osteopetrotic)
      rats: persistent metaphyseal sclerosis and the failure to restore subepiphyseal
      osteoclasts.
AB  - Toothless (tl), one of four osteopetrotic mutations in the rat, is characterized
      by few osteoclasts, undetectable bone resorption, and failure of correction by
      bone marrow transplantation. We recently reported that CSF-1 treatment improves
      these skeletal problems but that metaphyseal sclerosis persists. In the present
      study we demonstrate that optimal reduction of the skeletal sclerosis in tl rats
      following CSF-1 treatment has lower and upper dosage thresholds and that skeletal
      sclerosis returns after CSF-1 withdrawal. Osteoclasts increase significantly in
      tl rats after CSF-1 treatment, but compared to untreated normal littermates,
      histochemical staining for characteristic enzymes and osteoclast number is
      reduced and no osteoclasts appear in the subepiphyseal areas of long bones. These
      data are interpreted to mean that there are dosage limits to the beneficial
      skeletal effects of CSF-1, that persistent sclerosis is related to the failure to
      restore subepiphyseal osteoclasts, that osteoclast or progenitor populations may
      be deficient or differ in their responses to CSF-1, and that the defect in tl
      rats is not merely lack of a circulating, biologically active form of CSF-1.

PMID- 8274314
TI  - Transiliac bone biopsy.

PMID- 8274313
TI  - Age- and sex-related changes in iliac cortical bone mass and remodeling.
AB  - Iliac crest bone biopsies were obtained from 64 normal individuals (41 women and
      23 men) aged 19-90 (mean 48.2) years. Thirty-four were double-labeled with
      tetracycline before biopsy. The following variables were measured in all
      biopsies: biopsy core width (C.Wi), absolute (A.Ct.Wi) and fractional (F.Ct.Wi)
      cortical width, absolute (A.Cn.Wi) and fractional (F.Cn.Wi) cancellous width,
      cortical porosity (Ct.Po), osteon diameter (On.Dm), Haversian canal diameter
      (Ha.Ca.Dm), and wall thickness (W.Th). In the tetracycline-labeled biopsies the
      typical cortical remodeling cycle was reconstructed and the activation frequency
      was estimated. A negative cortical bone balance with aging was found in both
      sexes. In females F.Ct.Wi decreased (p < 0.02) with aging because of marrow
      expansion (p < 0.05). Furthermore, Ct.Po increased (p < 0.001) because of a
      decrease in W.Th (p < 0.01) and an increase in H.Ca.Dm (p < 0.001). In males the
      negative cortical bone balance with aging was exclusively caused by an increase
      in Ct.Po (p < 0.001) partially explained by an expanding H.Ca.Dm (p < 0.01). The
      On.Dm increased with aging (p < 0.01), but surprisingly, no fall in W.Th was
      observed. Reconstruction of the remodeling cycle did not reveal any significant
      difference between younger women and men. However, the activation frequency rose
      from 0.5 per year in premenopausal to 1.0 per year in postmenopausal women (p <
      0.001), giving rise to a high turnover state, an increase in the remodeling
      space, and thereby the porosity in the cortical bone immediately after menopause.
      The present study has shown a reduction in cortical bone mass in elderly people,
      compared with younger, which may be explained by an age-related remodeling
      imbalance. This reduction is further increased in women in the postmenopausal
      state because of a postmenopausal accelerated bone turnover.

PMID- 8274315
TI  - Presenting expert evidence in criminal proceedings.

PMID- 8274316
TI  - Research in general dental practice--problems and solutions.

PMID- 8274317
TI  - 'Postgraduate problems'.

PMID- 8274318
TI  - 'Periapical metastasis'.

PMID- 8274319
TI  - 'The amalgam controversy'.

PMID- 8274320
TI  - Partial-partial dentures!

PMID- 8274321
TI  - 'Active learning in the UK undergraduate dental course'.

PMID- 8274322
TI  - Oral economics.

PMID- 8274323
TI  - Host genes and dental caries.
AB  - With the attention now being given to molecular genetic analysis of cariogenic
      microorganisms, the role of host genes in influencing susceptibility to caries
      should not be forgotten. Increasing knowledge in this field will lead to
      identification of individuals at particular risk of dental decay and will help in
      planning rational strategies for management and prevention.

PMID- 8274324
TI  - The effect of two different local anaesthetic solutions on pain experience
      following apicectomy.
AB  - Post-operative pain experience following apicectomy of a single maxillary
      anterior tooth was compared in two groups of patients having this treatment under
      local anaesthesia. Twenty patients received 3.6 ml of 2% lignocaine with 1:80,000
      adrenaline and 23 patients the same volume of 1.5% etidocaine with 1:200,000
      adrenaline, as the local anaesthetic agent. Although soft tissue anaesthesia
      lasted significantly longer when etidocaine with adrenaline was used, pain
      experience and analgesic intake did not differ between regimens. Lignocaine with
      adrenaline produced better operating conditions as haemorrhage control was more
      effective and the quality of operative anaesthesia was more satisfactory than
      with etidocaine and adrenaline. The use of etidocaine with adrenaline offered no
      advantages over lignocaine with adrenaline when administered as infiltration
      anaesthesia for apical surgery.

PMID- 8274325
TI  - The use of adhesively retained gold onlays in the management of dental erosion in
      a child: a 4-year case report.
AB  - Tooth erosion, particularly in young people, presents a considerable challenge to
      restorative dentistry. A case of a 12-year-old is described where the use of
      minimal tooth preparation, precious metal onlays and a 4-META bonding system,
      together with dietary counselling, have provided a satisfactory result over 4
      years.

PMID- 8274326
TI  - Familial cold urticaria--a rare cause of lip swelling.
AB  - Cold urticaria is an unusual condition characterised by wealing of the skin or
      mucous membranes following exposure to cold. This report describes a presentation
      with recurrent lip swelling.

PMID- 8274327
TI  - Cutaneous horn occurring on the vermilion border of the lower lip.
AB  - A case of cutaneous horn of the lower lip is presented. The paper highlights the
      need for careful management of such lesions due to the high incidence of
      malignant or premalignant histology.

PMID- 8274328
TI  - Reflections of an MCCD/MGDS course participant 1991-92.

PMID- 8274329
TI  - [Watchdog shows claws. Interview by Kjell Arne Bakke].

PMID- 8274330
TI  - [Nursing is "big sister" in the health care system. Interview by Kjell Arne
      Bakke].

PMID- 8274332
TI  - [Nurses have poorest working environment].

PMID- 8274331
TI  - [Don't leave practical studies to the nurses. Interview by Kjell Arne Bakke].

PMID- 8274333
TI  - [Spokesman for patients. Interview by Siv Barstad].

PMID- 8274334
TI  - [Reform 94: new education in health care occupation].

PMID- 8274335
TI  - [Nursing under a different sky: West Kenya].

PMID- 8274336
TI  - [Nursing services omitted in parliamentary report. Interview by Kjell Arne
      Bakke].

PMID- 8274337
TI  - [Community must have its own midwife].

PMID- 8274338
TI  - Eight sources of manager derailment.

PMID- 8274339
TI  - Delegating responsibility for financial operations.

PMID- 8274340
TI  - Patient-centered unit redesign: an action approach.

PMID- 8274341
TI  - Assuring competence: building skills validation labs.

PMID- 8274342
TI  - Words of the '80s define the '90s.

PMID- 8274343
TI  - Nurses' guide to the drug development process and the current regulatory
      environment.
AB  - Health care professionals are frequently asked to answer patients' questions
      about how medications reach the market and the lengthiness of the process.
      Misconceptions about the process require nurses to understand how the Food and
      Drug Administration (FDA) enforces its laws, and how the agency works in the
      enforcement of its responsibilities. The purpose of this article is to
      familiarize nurses' with the FDA's history and the drug development process. In
      addition, nurses need to be familiar with the current environment at the agency
      and issues that are currently under debate (Franke, 1992).

PMID- 8274344
TI  - The use of alginates in the management of exudating, infected wounds: case
      studies.
AB  - The purpose of this article is to illustrate the use of alginate wound packing on
      difficult-to-manage wounds. Three case studies are presented with 18 photographs
      that illustrate the various stages of healing. All wounds were infected,
      malodorous, and heavily exudative when treatment was initiated.

PMID- 8274345
TI  - Genital herpes: clinical features, sources of information, recurrences, and
      treatment in young adults.
AB  - A descriptive study of 252 young adults with genital herpes recruited from
      newspaper advertisements in a metropolitan area on the West coast revealed gender
      differences in clinical features of the disease, perceived causes of recurrences,
      and treatments used. Stress was the most frequently perceived cause of
      recurrences. Although 68% of participants perceived nurses to be a source of
      information about the disease, only 25% perceived nurses as a source of the best
      information they had received. Development of nursing interventions based on the
      experience and perceptions of patients is needed.

PMID- 8274346
TI  - What's your assessment? Kaposi sarcoma.

PMID- 8274347
TI  - When the pregnant woman experiences itching.
AB  - It is important for dermatology nurses to know the presentation and outcome of
      the various dermatoses which are unique to pregnancy so that they may identify
      potential risks to the mother and fetus and evaluate future pregnancies.
      Differentiating features, adjunctive laboratory studies, and the medical
      implications regarding the risk of recurrence in a future pregnancy are examined
      in this article.

PMID- 8274349
TI  - Smoke and mirrors.

PMID- 8274348
TI  - Clinical application of the Braden Scale in the acute-care setting.
AB  - The Braden Scale for Predicting Pressure Sore Risk was designed to predict
      patients at risk of forming pressure sores and has been tested in a variety of
      settings. In two studies with a cumulative n of 199, the sensitivity was 100%
      using 16 as a cut-off and the specificity ranged from 64% to 90%. In this study
      of 361 patients in a large, tertiary, acute-care facility, the Braden Scale
      sensitivity was 73% and specificity was 91%. Using 16 as the cut-off point, this
      instrument would have over-predicted pressure sore formation, but, more
      importantly, inadequate preventative measures would have been provided for 27% of
      the patient population.

PMID- 8274350
TI  - Understanding Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos syndrome is an inherited condition in which the body produces
      defective collagen. Manifestations are highly variable, and include numerous skin
      abnormalities. Nurses play an important role in helping patients and their
      families live with this unusual disorder.

PMID- 8274351
TI  - Comparison of two devices for wound measurement.
AB  - Sixty leg ulcers were measured with two techniques, a common paper tape measure
      and a new technique, a plastic grid device. The plastic grid proved to be a
      reliable, valid, and feasible method to quickly assess wounds in a busy
      outpatient setting. The grid was superior to the tape measure in assessing large
      and/or irregular ulcers.

PMID- 8274352
TI  - Laser treatment of cutaneous malignancies.
AB  - The unique characteristics of lasers and their effects upon tissue form the basis
      for the medical use of lasers. As laser technology makes rapid strides and
      advances, it is important for dermatology nurses to understand the usefulness of
      the currently available lasers and the limitations and potentials of this mode of
      therapy for cutaneous malignancies.

PMID- 8274353
TI  - Skin lesions in Behcet's disease.
AB  - Behcet's disease is a rare, chronic disorder involving the small blood vessels.
      It is difficult to recognize and diagnose. Some manifestations of this disease
      include skin lesions, some of which are particular to Behcet's in conjunction
      with its other symptoms.

PMID- 8274354
TI  - What's your assessment? Pyogenic granuloma.

PMID- 8274355
TI  - Scabies: diagnosis and treatment.
AB  - Scabies is a common, severely pruritic, contagious disorder. Treatment must be
      careful and methodical to avoid continuing infestation. Patients and their
      contacts must be treated, and clothing changed. Failure to discover all the
      contacts leads to continuing spread of the disease.

PMID- 8274356
TI  - Role of magnesium as radiosensitizer in the in vitro radiolysis of aqueous
      solutions of guanosine-5'-monophosphate disodium.
AB  - A combination of Fourier Transform Infrared (FT-IR) spectroscopy and mass
      spectrometry (MS) was used to investigate the role of Mg2+ ions in gamma
      radiolysis of aqueous solutions of guanosine-5'-monophosphate disodium salt. The
      FT-IR intensity changes together with the mass spectra suggest the interaction of
      the magnesium atom with the base guanine at the N7 site. The decomposition
      limiting yield G(-5'-GMPNa2) in deaerated as well as in nitrous oxide saturated
      solutions, determined by measuring the absorbance at 253 nm, was found to be 0.6
      and 1.2 respectively. Comparison of these values with the corresponding limiting
      yields of 0.3 and 0.6 that were found in the absence of Mg2+ ions shows the
      sensitizing role of this ion in the radiolysis of the mononucleotide. This in
      vitro behaviour may result in more effective local therapy of tumour by gamma-ray
      irradiation in the presence of Mg2+, due to the 100 per cent sensitization of the
      radiolysis reaction. It remains to be seen whether this is also true in vivo.

PMID- 8274357
TI  - Modifying effect of 26-hydroxycholesterol on low-magnesium-induced
      atherosclerotic changes in the cultured human arterial smooth muscle cell.
AB  - This study investigated the modifying effect of 26-hydroxycholesterol (26-OHC) on
      low-Mg(2+)-induced atherosclerotic changes in human arterial smooth muscle cells.
      Cells were exposed to a medium containing a concentration of 142, 332, 665 and
      949 microM Mg2+ (as control) for the designed periods. Half the cells were
      simultaneously exposed to 10 micrograms/ml of 26-OHC. The results showed that the
      cytotoxicity of low Mg2+ and the stimulating effect of low Mg2+ on cytosolic free
      Ca2+ level and 45Ca2+ uptake were accentuated by 26 microns OHC. The significant
      increase of [3H]thymidine incorporation by Mg2+ level at and lower than 332 was,
      however, counteracted by 26-OHC. While an increased [3H]leucine incorporation
      occurred only at a level of 665 microM Mg2+, an additional increase of
      [3H]leucine incorporation also occurred at a level of 142 microM Mg2+ in the
      presence of 26-OHC. We suggest that 26-OHC could modify the atherogenic effect of
      low Mg2+.

PMID- 8274358
TI  - Oxalate metabolism in magnesium-deficient rats.
AB  - Male weanling rats were maintained on magnesium-deficient diet for 30 d and
      compared with pair-fed control rats fed magnesium-supplemented diet. Magnesium
      deficiency led to slow growth and finally to a significant decrease in body
      weight (P < 0.001) accompanied by a significant hypomagnesaemia, hypomagnesuria
      and hyperoxaluria (P < 0.001 in each case) in experimental rats as compared to
      the control rats. Magnesium deficiency altered the glyoxylate metabolism in the
      liver and kidney mitochondria by significantly decreasing glyoxylate oxidation
      (by 26 per cent in liver and 17 per cent in kidney) and activity of alpha
      ketoglutarate:glyoxylate carboligase enzyme (by 35 per cent in liver and 27 per
      cent in kidney) in the experimental animals. A significant increase in the
      specific activities of glycolic acid oxidase (P < 0.001) and glycolic acid
      dehydrogenase (P < 0.01) and a significant decrease in alanine transaminase (P <
      0.01) was also observed in magnesium-deficient rats. No change in liver and
      kidney lactate dehydrogenase was observed. Thus magnesium deficiency in rats
      leads to accumulation of glyoxylate in the tissues, a part of which is converted
      into oxalate, thereby promoting hyperoxaluria.

PMID- 8274359
TI  - Prophylactic effect of high magnesium intake in rabbits exposed to prolonged lead
      intoxication.
AB  - The ability of magnesium to prevent chronic lead intoxication was investigated by
      simultaneous oral treatment with lead and magnesium. Rabbits were intubated
      daily, for 28 d, with aqueous solutions of lead nitrate and magnesium acetate to
      give a lead dose level of 20 mg/kg and a magnesium dose level of 40 mg/kg body
      weight per day. A control group was treated only with lead. Supplementation with
      magnesium was found to be effective in reducing the lead content in blood and
      enhancing lead elimination via the urine. Results suggest that oral treatment
      with magnesium could possibly prevent deposition of lead in the body.

PMID- 8274360
TI  - Is magnesium content in erythrocytes suitable for evaluating cation retention
      after oral physiological supplementation in marginally magnesium-deficient
      subjects?
AB  - In this study, the effects of oral magnesium supplementation were evaluated on
      plasma, erythrocyte, and urinary cation levels. The study was carried out with an
      open, cross-over and randomized design. Healthy subjects received two sachets per
      day of magnesium (366 mg Mg2+/d) for two 28 d cycles, separated by a 3-week
      washout interval. Magnesium concentrations were measured before the
      supplementation and at weekly intervals during the treatment. Urinary excretion
      of Mg was significantly increased during supplementation, with no differences
      among the weeks examined. Only small increases in plasma magnesium occurred, and
      values returned to the prestudy levels before the end of supplementation. The
      increase in erythrocyte magnesium, however, was statistically significant; this
      trend suggests the existence of a saturable mechanisms, which prevents any
      possible magnesium overload during oral supplementation. We conclude that
      erythrocytes might be considered a suitable index for evaluating the
      bioavailability of magnesium salts in marginally magnesium-deficient subjects.

PMID- 8274362
TI  - Absence of correlation between magnesium and riboflavin status.
AB  - Erythrocyte magnesium and glutathione reductase activity coefficient (EGR-AC),
      reflecting vitamin B-2 status, were assessed in 11 athletes, 20 patients with
      fibromyalgia, 18 patients with hypothyroidism, and 13 controls. No correlation
      was demonstrated between erythrocyte magnesium and EGR-AC.

PMID- 8274361
TI  - Trabecular bone density in a two year controlled trial of peroral magnesium in
      osteoporosis.
AB  - Since magnesium regulates calcium transport, and magnesium replacement in
      magnesium-deficient postmenopausal patients resulted in unexpected improvement in
      documented osteoporosis, we investigated the effect of magnesium treatment on
      trabecular bone density in postmenopausal osteoporosis. Thirty-one postmenopausal
      patients (mean age +/- SD = 57.6 +/- 10.6 years), consecutively admitted to the
      Back Rehabilitation Unit with musculoskeletal pain of non-malignant origin and
      bone density values of < or = 1.19 g/cm3 (measured by Compton Bone Densitometer),
      received two to six tablets daily of 125 mg each of magnesium hydroxide
      (Magnesium Magma USP/; 'Mazor', Israel) for 6 months and two tablets for another
      18 months in a 2 year, open, controlled therapeutic trial. Twenty-three symptom
      free postmenopausal women (mean +/- SD = 61.2 +/- 6.2 years) whose bone density
      was concurrently assessed at the same laboratory and who were found to have
      osteoporosis but refused treatment, served as controls. No new fractures
      occurred. Twenty-two patients (71 per cent) responded by a 1-8 per cent rise of
      bone density. The mean bone density of all treated patients increased
      significantly after 1 year (P < 0.02) and remained unchanged after 2 years (P >
      0.05). The mean bone density of the responders increased significantly both after
      one year (P < 0.001) and after 2 years (P < 0.02), while in untreated controls,
      the mean bone density decreased significantly (P < 0.001). The disparity between
      the initial mean bone density and bone density after one year in all osteoporotic
      patients and in the responders differed significantly from that of the controls
      (both P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274363
TI  - Regulation of sodium and potassium pathways by magnesium in cell membranes.
AB  - Magnesium plays an important role in a large number of cellular processes by
      acting as a cofactor in enzymatic reactions and transmembrane ion movements.
      Magnesium is a modulator of Na,K ion transport systems in numerous tissues. In
      this study, the interactions between magnesium and Na,K pathways are described.
      In the paracellular pathway, Na,K transports are generally increased by Mgo. In
      the cellular pathway, there are various processes: (1) Potassium channels-Mgi
      blocks the outward currents, first by interfering with the passage of K+ ions and
      inducing rectification of the channel current-voltage relationship, and secondly
      by completely blocking the channel pore and reducing the channel open
      probability: Mgo increases the K+ channel permeability in a leaky membrane. (2)
      Sodium channels-Mgi blocks outward currents in a voltage- and dose-dependent
      manner, acts as a fast blocker by screening of surface charges, and produces an
      open channel block in several Na+ channels; Mgo increases Na+ transport in toad
      bladder and human amnion at high concentration by acting on the driving force of
      the sodium pump. (3) Na/K pump-Mgi and Mgo stimulate the Na/K exchange at low
      concentration and inhibit it at high concentration, by a stabilization of E2
      forms of the enzyme which would reduce the rate of turnover of the pump. (4) Na-K
      2Cl cotransport increasing Mgo concentration stimulates this system in red cells
      and human amnion, and the bumetadine-sensitive K+ transport is sensitive to Mgi
      (5) Kcl cotransport-The increase in Mgi inhibits this cotransport. (6) Na-H
      antiport-Na/H exchange responds to manipulations of cell magnesium but the effect
      is probably not a direct one; magnesium is required not for the transport process
      per se, but for the transduction of the volume stimulus (7) H-K pump Mg activates
      this system. (8) Na-Ca antiport-The activity of this antiporter is inhibited by
      Mgo; the inhibition by magnesium is competitive with calcium. (9) Na-Mg exchange
      in this system, the Na+ gradient provides the energy for net Mg2+ extrusion. In
      conclusion, intracellular and extracellular magnesium may be an important
      physiological regulator of the sodium and potassium pathways in the cell.

PMID- 8274364
TI  - Magnesium and arachidonic acid metabolism.
AB  - The arachidonic acid content of plasma lipoproteins is altered during dietary
      magnesium deficiency, although the tissue arachidonic acid content seems to be
      unchanged. The primary event triggering these changes is probably the loss of
      extracellular Mg2+, as it is not clear whether dietary magnesium deficiency
      produces loss of intracellular Mg2+. In the isolated rabbit heart, in vitro
      perfusion conditions which produce loss of intracellular Mg2+ also result in
      disturbances of arachidonic acid metabolism. The metabolism of exogenous
      arachidonic acid to prostaglandins is increased without changing the Km or Vmax
      of cyclo-oxygenase. The incorporation of arachidonic acid into tissue
      phospholipids is significantly reduced, although the incorporation of oleate,
      stearate, and linolenate is either increased or unchanged. These data indicate
      that the activity of the enzymes (CoA synthetases and acyl transferases) which
      mediate arachidonate incorporation is reduced during Mg2+ depletion. Since
      protein-kinase-C-mediated phosphorylation of both CoA synthetase and acyl
      transferase reduces their activity, and since protein kinase C has an Mg2+
      binding site, it is possible to speculate that loss of intracellular Mg2+ may
      lead to the activation of protein kinase C, with the consequent reduction of
      arachidonic acid reacylation enzyme activity.

PMID- 8274365
TI  - Fatty acid profile, fibre content and high magnesium density of nuts may protect
      against risk of coronary heart disease events.

PMID- 8274366
TI  - Guidelines NCI Cancer Education Grant Program. National Cancer Institute.

PMID- 8274367
TI  - Abraham Flexner--a crusader against medical maleducation.
AB  - The Flexner Report, one of the most cited publications in medical education,
      describes the site-visits to 163 medical schools in 40 American states, in terms
      of admission requirements, number of students, number of faculty, etcetera. The
      Flexner Reports (there are three!) are still worth reading. For instance, Flexner
      holds a plea for problem orientation. "The student is to collect and to evaluate
      facts. The facts are locked up in the patient. To the patient, therefore, he must
      go." The impossibility of obtaining encyclopaedic knowledge requires medical
      students to adopt a scientific attitude; this calls for dedicated teachers, not
      necessarily from the research establishment. Flexner recommended the closing down
      of 124 medical schools, not only because of the deplorable quality, but also
      because of the disproportionate geographical distribution, and (most of all)
      because of the enormous overproduction of medical doctors. Flexner's significance
      as a medical educator is illustrated by a discussion of the role of the teacher
      and the nature of medical education. Learning, not teaching, is what it is all
      about. It is argued that cancer education can learn from Flexner's insights.

PMID- 8274368
TI  - Efficacy of interactive, automated programmed instruction in nutrition education
      for cancer prevention.
AB  - Ninety-two undergraduates were assigned into groups to evaluate the effectiveness
      of interactive, computer-delivered programmed instruction for nutrition education
      on the topic of diet and cancer compared to traditional passive modes of
      instruction. Students were monitored for knowledge gains by means of a single 50
      item test and an application task, using a 4-day diet record, administered 4
      weeks prior to and 3 weeks after intervention. Results indicated that although
      subjects in the interactive group took nearly twice as long to complete the
      program, having the opportunity to respond to program blanks, this group produced
      significantly greater knowledge gains and lowered their fat intake by 41.8%
      compared to 26.1% reduction in fat intake in the noninteractive computer group
      and 18.6% in the passive prose text groups. Results suggest that interactive,
      computer-delivered, programmed instruction can be a very important adjunct to
      health care and cancer prevention programs at high schools and university
      settings.

PMID- 8274369
TI  - Problems encountered in teaching the use of the 65 cm flexible sigmoidoscope in a
      surgical oncology training program.
AB  - Flexible sigmoidoscopy after age 50 has been recommended by the American Cancer
      Society for colorectal cancer screening. A questionnaire to assess the
      difficulties encountered in learning to perform this procedure was given to 19
      surgical oncology fellows after a 3-month rotation in the Division of Colorectal
      Surgery. Sixteen (84%) trainees related that between 10-20 flexible
      sigmoidoscopies were necessary before they felt competent. The most difficult
      aspect of learning flexible sigmoidoscopy was the torquing technique followed by
      the ability to determine the location of the proximal bowel lumen. All 19
      trainees rated the ability to recognize pathology as not difficult. In this group
      of surgical trainees, the mean number of flexible sigmoidoscopy performed before
      competency was established was 15; torquing the shaft of the sigmoidoscope was
      the most difficult aspect to learn. The majority of the trainees recorded that
      following the performance of 15-20 endoscopies, torquing became easier.

PMID- 8274370
TI  - The clinical use of genealogical techniques in cancer investigations: a
      questionnaire survey.
AB  - This survey of physicians covered their attitudes toward, knowledge of, and
      diligence in the integration of family history and its application to the care of
      patients with multiple atypical nevi. The respondents recognized the importance
      of a personal or family history of malignant melanoma and a medical genealogical
      investigation of the kindred, but they gave little attention to pursuing an in
      depth genetic investigation of their patients' kindred. The data suggest that
      curricula in medical schools need to include not only the clinical expressions of
      genetic disorders but must emphasize the physicians' behavior skills pursuing
      genealogical investigative techniques in the preventive health care of patients
      and their kindred with hereditary cancers.

PMID- 8274371
TI  - The Ohio Cancer Information Service: technology transfer on clinical trials and
      other measures of cancer control.
AB  - We examined trends in caller queries on tobacco, mammography, Pap tests, and
      clinical trials to the NCI-sponsored Cancer Information Service (CIS) of Ohio via
      its toll free telephone number (1-800-4-CANCER) during 1986-1991. Calls on NCI
      approved clinical trials and treatment protocols tripled during the study period
      (from 6% in 1986 to 20% in 1991, p < 0.01) primarily due to counselor-initiated
      (proactive) recommendations and actions. Calls on breast cancer showed a
      significant increase whereas calls on respiratory system cancers showed a decline
      over the time period. There was also a dramatic increase in calls on mammography,
      reflecting the impact of national and local promotion of breast screening.
      Queries on tobacco use and Pap tests declined, perhaps due to a perceived
      saturation effect of public education on these two topics. Our results support
      the use of CIS as a technology transfer system.

PMID- 8274372
TI  - A breast cancer support group: activities and value to mastectomy patients.
AB  - This study surveys the reasons women attend a breast cancer support group as well
      as the perceived benefits of attending one. The hope of receiving and giving
      emotional support and of obtaining increased information were the largest single
      factors in attendance. Our results indicate that these hopes are realized.
      Patients should be offered the opportunity to attend support groups, as they
      provide added and needed assistance, especially in the areas of new information
      on cancer and coping with its psychosocial sequelae.

PMID- 8274373
TI  - Magnetic resonance imaging of the foot and ankle.
AB  - Magnetic resonance imaging (MRI) of the foot and ankle is useful for the
      diagnosis and staging as well as the surgical planning of multiple disorders:
      first, for osseous injury, particularly stress fractures and occult fractures,
      which appear like bone bruises but behave more like fractures. Then, for the
      Achilles tendon, MR is useful for staging the chronicity and extent of damage, as
      well as whether the tendon can be surgically repaired or reconstructed. For the
      diagnosis of posterior tibialis tendon tears and injuries, MR is an important
      tool in surgical planning. Often, MR is helpful for the diagnosis of peroneal
      tendon injury, including dislocations and peroneal splits, two entities that are
      seen to affect only the peroneal tendons. MR helps in the evaluation of avascular
      necrosis in any bone secondary to various systemic causes, particularly following
      talus fractures. MR has also been utilized to assess ankle sprains with
      complications, such as the ankle impingement syndrome, the sinus tarsi syndrome,
      and chronic instability, and to diagnose osteomyelitis (since the typical patient
      also has neuropathic disease bone, scintigraphy is invariably abnormal). MR is
      promising for the evaluation of reflex sympathetic dystrophy and is as useful for
      the evaluation of bone and soft tissue tumors as it is elsewhere in the skeleton.
      MR helps to characterize the biological aggressiveness of the tumor as well as
      its extent and therefore aids in surgical planning.

PMID- 8274374
TI  - Magnetic resonance imaging of urinary bladder cancer: an overview and new
      developments.
AB  - The role of magnetic resonance (MR) imaging in the management of carcinoma of the
      urinary bladder is reviewed and illustrated. In vivo and in vitro MR images of
      the normal urinary bladder, carcinoma, and surrounding structures are presented.
      Factors for optimal MR imaging of urinary bladder carcinoma are reviewed. Pulse
      sequence optimization, (endorectal) surface coils, and other new developments
      such as fast spin echo, subtraction turbo-fast low angle shot (FLASH), three
      dimensional rapid acquisition gradient echo sequences, and the use of contrast
      agents are discussed. Finally, the value of MR imaging in staging urinary bladder
      carcinoma is compared with clinical staging, staging based on findings from
      computed tomography and intravesical sonography.

PMID- 8274375
TI  - Imaging at high magnetic fields: initial experiences at 4 T.
AB  - This article reviews the preliminary experiences and the results obtained on the
      human brain at 4 T at the University of Minnesota. Anatomical and functional
      images are presented. Contrary to initial expectations and the early results, it
      is possible to obtain high-resolution images of the human brain with exquisite T1
      contrast, delineating structures especially in the basal ganglia and thalamus,
      which were not observed clearly in 1.5-T images until now. These 4-T images are
      possible using a new approach that achieves maximal contrast for different T1
      values at approximately the same repetition time and has built-in tolerance to
      variations in B1 magnitude. For functional images, the high field provides
      increased contribution from the venuoles and the capillary bed because the
      susceptibility-induced alterations in 1/T2* from these small-diameter vessels
      increase quadratically with the magnitude of the main field. Images obtained with
      short echo times at 4 T, and by implication at lower fields with correspondingly
      longer echo times, are expected to be dominated by contributions from large
      venous vessel or in-flow effects from the large arteries; such images are
      undesirable because of their poor spatial correspondence with actual sites of
      neuronal activity.

PMID- 8274376
TI  - Normal venous anatomy and physiology of the lower extremity.
AB  - Venous disease of the lower extremities is common but is often misunderstood. It
      seems that the focus is on the exciting world of arterial anatomy and pathology,
      while the topic of venous anatomy and pathology comes in second place. However,
      venous diseases such as chronic venous insufficiency, leg ulcers, and varicose
      veins affect much of the population and may lead to disability and death. Nurses
      are often required to answer complex questions from the patients and his or her
      family about the patient's disease. Patients depend on nurses to provide accurate
      information in terms they can understand. Therefore it is important to have an
      understanding of the normal venous system of the legs before one can understand
      the complexities of venous diseases and treatments. This presents an overview of
      normal venous anatomy and physiology.

PMID- 8274377
TI  - The management of chronic venous disease.
AB  - Chronic venous disease represents a spectrum of problems ranging from the merely
      cosmetic to disabling venous ulcers. Chronic venous insufficiency can result in
      disfigurement, disability, and a financial burden on the patient and society.
      Delivery of optimal care of patients with venous disease requires a thorough
      understanding of this complex system and of current methods of diagnosis and
      treatment. Successful outcome of treatment depends on appropriate patient
      selection, meticulous surgery, outstanding nursing care, and patient education.

PMID- 8274378
TI  - Vascular consequences of smoking and benefits of smoking cessation.
AB  - Cigarette smoke contains more than 4000 active compounds. The most common of
      these are nicotine and carbon monoxide. The inhalation of these compounds causes
      an immediate and active response in the human body. Atherosclerosis is thought to
      be related to smoking in some direct or indirect manner. Although no direct link
      has been proved, the risk for experiencing atherosclerotic changes in vessel
      walls seems to increase with smoking, especially in the presence of other risk
      factors. These include a high-fat diet, heredity, and diabetes. The relationship
      between smoking and coronary artery and peripheral vascular disease has been
      suggested by clinical studies with animals and human subjects. Although the
      smoking population in the United States has diminished in size, the number of
      teen and women smokers has continued to increase. Resources for those who desire
      to quit smoking are available in most health care settings. Success depends on
      many factors, including support networks, patient knowledge, and the method
      selected for cessation. The vascular nurse can support the patient in choosing a
      healthier life-style that is free of smoking.

PMID- 8274379
TI  - The research process.

PMID- 8274380
TI  - Vascular rehabilitation: structured, yet flexible and creative.

PMID- 8274381
TI  - Vertebral artery reconstruction in a setting of extensive cerebrovascular
      disease.

PMID- 8274382
TI  - Message from the president--nursing and industry: opportunity or opposition?

PMID- 8274383
TI  - Evaluation of a protocol on the care and management of a neurological patient
      with seizures.
AB  - In the hope of discovering a user friendly resource applicable to the Clinical
      practice of all nurses, staff at Vancouver General Hospital experiment with the
      use of nursing protocols. Last year nurses on the neurological unit proposed that
      effective management of seizure patients could be further facilitated when
      expected standards of care were properly developed, implemented, utilized and
      evaluated in the form of a nursing protocol. A two phase study was conducted
      attempting to compare those patients admitted to the unit one year prior to the
      use of the protocol, with those admitted for one year following its
      implementation. The results of this study will be presented in relation to the
      effectiveness of the protocol on patient outcomes. As well, the unit nurses'
      response to working with the protocol will be reviewed.

PMID- 8274384
TI  - Headache--defined.
AB  - Headache is one of man's most common afflictions. Increasing interest from the
      general population has contributed to the recent surge in research. This research
      relates to etiology or pathophysiology, treatment and impact of society. Headache
      can be a minor symptom or a symptom of serious underlying disease. As nurses,
      either in a health care facility or in our communities, we have a responsibility
      to keep abreast of current theories and treatments. Both presenters are currently
      involved in clinical trials of new headache medications for both children and
      adults. Behavioural Objectives: 1. Understand when a headache is a serious
      symptom and warrants further investigation. 2. Identify the different types of
      headache. 3. Describe the etiology of headache and its physical and psychological
      manifestations in child and adults with a particular emphasis on migraine. 4.
      Gain appreciation for the role of the clinical trials nurse.

PMID- 8274385
TI  - I have been asked to testify as an expert witness in a neuroscience lawsuit
      involving the standard of nursing care delivered.

PMID- 8274386
TI  - Neurosurgical short term rehabilitation on an acute neurology unit.
AB  - The need for a focused rehabilitation program for neurosurgical clients was
      identified when the Regional Neurosurgical Service was developed at The
      Mississauga Hospital. This paper will discuss the development, implementation and
      evaluation of a Neurosurgical Short-Term Rehabilitation program. Objectives 1.
      Describe the development of a Neurosurgical Short-Term Rehabilitation program. 2.
      Identify criteria for admission and discharge to the program. 3. Describe the
      role of the primary care giver in the rehabilitation setting. 4. Outline the role
      of the R. N. as the coordinator of the multidisciplinary team. 5. Analyze the
      results of the patient questionnaire as an evaluation tool.

PMID- 8274387
TI  - Local treatment of dystonia and spasticity with injections of botulinum-A toxin.
AB  - The use of botulinum-A toxin will be described in two conditions--the
      extrapyramidal syndrome of dystonia and the pyramidal deficit, spasticity. There
      is no cure for dystonia and its cause is unknown. Drug therapy is unpredictable
      and dose-limiting side effects frequently occur with little or no alleviation of
      symptoms. Spasticity of adductor muscles in the lower limbs causes profound
      disability and major nursing problems in patients with chronic disorders of the
      pyramidal tract. As in the case with dystonia, drug therapy is unsatisfactory. At
      the UBC Movement Disorders Clinic treatment with botulinum-A has been applied to
      over 400 patients since 1985. The results of the first studies using this
      treatment in spasmodic torticollis (the most common form of focal dystonia) and
      spasticity (in late stage multiple sclerosis) will be discussed. As well the
      effects of long term treatment will be addressed. Botulinum-A toxin is approved
      treatment for strabismus, blepharospasm and hemifacial spasm. Approval for its
      use in other focal dystonias is anticipated. The very nature of the agent used
      for treatment requires that patients be well prepared and reassured before they
      undergo their first treatment. There is a wide gulf between the patients'
      preconceived notions about the treatment and reality.

PMID- 8274389
TI  - How acceptable are "cover orders"?

PMID- 8274388
TI  - Tourette syndrome: a psychoeducational presentation.
AB  - Tourette Syndrome (TS) is a neurological disorder with onset prior to age 21. The
      wide range of difficulties associated with TS present significant barriers to
      both the positive school functioning of students with TS and the ability of their
      teachers and peers to cope with the sometimes difficult classroom behavior which
      results from this syndrome. Since TS children with teachers knowledgeable about
      TS and its effects on learning fare better than those whose teachers are not
      knowledgeable, dissemination of this information to school personnel is crucial.
      Health teaching is a significant contribution within the nursing role. In order
      to ameliorate some of the stressors and academic problems experienced by children
      and adolescents with TS, the TS Clinic of St. Boniface General Hospital is
      composed of a multidisciplinary team whose mandate includes the provision of
      educational awareness audiovisual presentations to schools and the general
      community throughout Manitoba. This presentation will include the historical,
      psychosocial, educational, symptomatological, and treatment aspects of TS.

PMID- 8274390
TI  - What is "nursing malpractice"?

PMID- 8274391
TI  - When neurological symptoms are not what they appear: the challenge of caring for
      patients with conversion disorders.
AB  - Conversion Disorders involve the psychogenic loss or disturbance of sensory,
      motor or other physical functions in a manner suggestive of neurologic or other
      somatic disease but without any actual finding of the latter. These problems are
      subconscious, with patients not being able to control their symptoms. Jean-Marie
      Charcot, in the 19th century, was fascinated with this disorder and his work,
      followed by that of Sigmund Freud, laid the foundation for our modern concept of
      Conversion Disorder. Multiple Sclerosis, with its fluctuating and unpredictable
      symptoms has frequently been erroneously diagnosed in these cases. The often
      bizarre, flamboyant presentations, while interesting, pose many difficult and
      complex management problems. This paper will describe three of the more severe
      and disabled examples of this condition seen in the London Multiple Sclerosis
      Clinic and an attempt will be made to uncover common patient characteristics.
      Current thoughts regarding the management of these patients will be outlined, the
      emphasis being on helping neuroscience nurses develop an approach which is
      informed, positive and compassionate.

PMID- 8274392
TI  - New developments in the treatment of SAH-induced cerebral vasospasm.

PMID- 8274393
TI  - Quadriplegia: focus on rehabilitation.
AB  - Spinal cord injury resulting in quadriplegia is one of the most devastating types
      of injury. The rehabilitation process actually begins at the time of injury.
      Emphasis on independence, however, is usually not a major factor until the client
      reaches the rehabilitation unit. This paper will focus on the rehabilitation
      management of a client with quadriplegia. Nursing interventions and teaching
      related to skin care, bowel and bladder care, nutrition, mobility, hygiene, and
      dressing will be discussed. Discharge planning, an integral component of the
      rehabilitation process, will also be addressed.

PMID- 8274394
TI  - Oh, Suzanna! A nursing challenge.
AB  - Suzie, a ten year old child well known on our pediatric neuroscience ward at a
      children's hospital in British Columbia, was admitted in August 1991 for
      continuing seizures and unmanageable behaviour after her fourth epilepsy surgery.
      She was to remain with us for a total of nine months. Very soon, it became
      apparent that we had an untenable situation on the ward. On the one hand, seizure
      control was poor and Suzie required hospitalization to adjust her medications and
      to treat frequent episodes of status epilepticus. On the other hand, her
      behaviour was seriously disruptive to other patients and staff, as well as
      presenting a safety concern. Negative behaviours fell into three categories-
      disinhibition, aggression and hyperactivity. Through slides and video tape, we
      will introduce Suzie and describe the progression of her disease. We will
      discuss, using a Nursing Case Management Model, how we took over her care,
      accessed community resources and eventually even accompanied her to Montreal for
      a right hemispherectomy. The "Suzie Experience" forced administration and staff
      to devise creative solutions and empowered nurses on the ward to implement new
      and unique strategies.

PMID- 8274395
TI  - Hyperventilation in head injury does it do more harm than good?
AB  - During the past decade the management of clients with severe head injuries has
      been influenced by the use of hyperventilation. Increased intracranial pressure
      (I.C.P.) is the major cause of death following head injury and outcome has been
      linked to the ability of the practitioner to control intracranial hypertension.
      Hyperventilation is one method that is frequently employed to control increases
      in I.C.P. There is no doubt that hyperventilation effectively reduces
      intracranial pressure, but controversy surrounds the influence that this
      procedure may inflict upon the cerebral hemodynamic reserve (C.H.R.). The
      literature indicates that in spite of normal cerebral perfusion pressure,
      associated with raised I.C.P., that C.H.R. may be compromised. This paper will
      examine the controversy that surrounds the use of hyperventilation in the client
      with severe head injury.

PMID- 8274396
TI  - Posttraumatic seizures: consensus and controversies.
AB  - Seizures after traumatic brain injury may cause acute deterioration in level of
      consciousness, signal the presence of significant intracranial pathology, herald
      potentially lethal status epilepticus and carry some risk for the development of
      a chronic disorder. Specific implications of immediate, early and late seizures
      are different and vary across age groups. While there is a consensus to manage
      status epilepticus aggressively, and some agreement to treat a seizure once it
      has begun, no such unanimity exists about management of patients who have one or
      more seizures after injury. This article identifies controversies about seizures
      that occur after traumatic brain injury in paediatric and adult populations. It
      concludes with a summary of research imperatives for the future.

PMID- 8274397
TI  - Hope as a coping strategy for the spinal cord injured individual.
AB  - This case study described how one spinal cord injured individual used hope as a
      coping strategy. Using observations and unstructured interviews, the indicators
      of hope were explored, as well as how hope was sustained over time and during
      crises. Data were gathered while nursing the individual, and his family using the
      McGill Model of Nursing. Qualitative data analysis revealed four categories which
      reflected indicators of hope (focusing on progress, positive interpretation,
      selective attention, goal setting), and seven categories of how hope was
      sustained (family responsibility, meaning in life, significant others,
      uncertainty of physiological status, past experience, goal attainment). Analysis
      of data also revealed that hope was goal directed, and hope was based on the
      reality perceptions of the individual. Over time, all indicators of hope were
      gradually displayed more often, and there was a gradual increase in focus on the
      meaning in life, family responsibility and goal achievement to sustain hope.
      Implications for nursing and research are suggested.

PMID- 8274398
TI  - What are the legal requirements for documenting nurse's notes in the patient's
      hospital chart?

PMID- 8274399
TI  - Ligand-dependent conformational changes in thyroid hormone and retinoic acid
      receptors are potentially enhanced by heterodimerization with retinoic X
      receptor.
AB  - Recently, many lines of evidence have been accumulated indicating that thyroid
      hormone receptor (TR) and retinoic acid receptor (RAR) undergo a ligand-dependent
      conformation change. Since most of these results were obtained by either gel
      shift assay or circular dichroism spectroscopic studies, it was not clear which
      part of the receptor bore the major conformational change. Moreover, it is not
      clear whether the formation of heterodimer between TR or RAR and retinoic X
      receptor (RXR) has any effects on this structural change. Utilizing partial
      proteolytic analysis, we demonstrated that thyroid hormone and retinoic acid
      induce a specific protease-resistant conformation to their cognate receptors.
      Studies of various deletion mutants reveal that the entire ligand binding domain
      of these receptors is involved in this change, and suggest that ligand may induce
      a more compact structure in its binding domain. Evidence from native gel
      electrophoresis supports this notion. This conformational change occurs in the
      absence of DNA and occurs independently of other domains in the receptor.
      Heterodimerization between TR or RAR and the RXR has little effect on receptor
      conformation in the absence of hormone but does enhance the ligand-dependent
      structural change. Interestingly, dual hormone treatment, i.e. thyroid hormone
      and 9-cis RA, intensifies this enhancement. We suggest that the observed protease
      resistant conformation may introduce a different configuration to the receptor
      and therefore may affect the receptor in various ways, but most likely is
      involved in converting the receptor from a negative regulator to a positive
      activator.

PMID- 8274400
TI  - An assessment of the role of domain F and PEST sequences in estrogen receptor
      half-life and bioactivity.
AB  - The estrogen receptor (ER) is a rapidly turning over protein, with a half-life of
      ca. 3-4 h in estrogen target cells. Sequence analysis of the human ER reveals a
      putative PEST sequence, sequences rich in proline (P), glutamic acid (E), serine
      (S) and threonine (T), in the carboxy-terminal F domain of the protein. Since
      PEST sequences have been implicated in the rapid turnover of some proteins, we
      have used site-directed mutagenesis to investigate the role of the F region
      containing PEST residues in the stability and bioactivity of the receptor. A
      truncated form of ER lacking the last 41 amino acids of the protein and
      encompassing the PEST sequences (amino acids 555 to 567) was made by mutagenesis
      of the ER cDNA. Pulse-chase experiments, involving immunoprecipitation of
      [35S]methionine/[35S]cysteine labeled receptors or of receptors covalently
      labeled with tamoxifen aziridine followed by gel electrophoresis, were used to
      determine the half-life of the wild-type and truncated ERs. These experiments
      showed that the turnover rate of the receptors expressed in Chinese hamster ovary
      and monkey kidney (COS-1) cells was 3 to 5 h and that elimination of the PEST
      residues did not have a significant effect on the degradation rate of the
      protein. Moreover, deletion of the last 41 amino acids (F domain) of the ER did
      not affect transactivation ability, ligand binding affinity, or the
      phosphorylation pattern of the receptor. Therefore, the role of domain F in ER
      function remains unclear, but it is not a determinant of the relatively rapid
      rate of ER turnover in cells.

PMID- 8274401
TI  - Molecular cloning of multiple cDNAs encoding human enzymes structurally related
      to 3 alpha-hydroxysteroid dehydrogenase.
AB  - Rat liver 3 alpha-hydroxysteroid dehydrogenase cDNA was previously cloned by us.
      In this study, we used the rat cDNA as the probe to screen a human liver lambda
      gt11 cDNA library. A total of four different cDNAs were identified and sequenced.
      The sequence of one of the cDNAs is identical to that of the human chlordecone
      reductase cDNA except that our clone contains a much longer 5'-coding sequence
      than previously reported. The other three cDNAs display high degrees of sequence
      homology to those of both rat 3 alpha-hydroxysteroid dehydrogenase and human
      chlordecone reductase. Because 3 alpha-hydroxysteroid dehydrogenase and human
      chlordecone reductase belong to the aldo-keto reductase superfamily, we named
      these human clones HAKRa to HAKRd. Northern blot analysis showed that the liver
      expresses the highest levels of all four clones. Expression of all four clones
      was also detected in the brain, kidney, lung, and testis, whereas the placenta
      expressed only the messenger RNA for HAKRb. Genomic blot analysis using HAKRb as
      the probe detected multiple DNA fragments hybridized to the probe and a high
      degree of restriction fragment length polymorphism, suggesting the complexity of
      this supergene family.

PMID- 8274402
TI  - Localization of the approximately 12 kDa M(r) discrepancy in gel migration of the
      mouse glucocorticoid receptor to the major phosphorylated cyanogen bromide
      fragment in the transactivating domain.
AB  - The intact wild-type mouse glucocorticoid receptor has a theoretical molecular
      weight of approximately 96 kDa based on amino acid sequence, but on SDS
      polyacrylamide gel electrophoresis it migrates as a protein of approximately 98
      kDa. It is not known where the unusual primary structure or covalent modification
      responsible for this anomalous migration is located within the amino acid chain.
      In the course of examining the pattern of fragmentation of 32P-labeled
      glucocorticoid receptors from Chinese hamster ovary (CHO) cells containing
      amplified mouse receptor cDNA, we have found a localized region in the amino
      terminal half of the receptor that accounts for this anomalous behavior. Cyanogen
      bromide treatment of the intact receptor produces a 23.4 kDa (theoretical)
      fragment consisting of residues 108-324 and containing all of the identified
      phosphorylated serines within the receptor. We find that the only large
      resolvable 32P-labeled receptor fragment produced after complete cyanogen bromide
      cleavage of intact receptors migrates with an apparent molecular weight of
      approximately 35 kDa. Because the apparent difference between the theoretical and
      the experimentally observed molecular weights of this cyanogen bromide fragment
      is essentially the same as the difference between the theoretical and
      experimental molecular weights of the intact mouse glucocorticoid receptor, we
      propose that some feature lying within this fragment accounts for slower
      migration. Although the existence of an additional phosphorylation site lying
      within the 15 kDa tryptic receptor fragment containing the DNA-binding domain has
      been contested, we also demonstrate that this fragment of the mouse
      glucocorticoid receptor is phosphorylated in vivo upon incubation of CHO cells in
      growth medium containing [32P]orthophosphate.

PMID- 8274403
TI  - Regulation of estrogen receptor protein and messenger ribonucleic acid by
      estradiol and progesterone in rat uterus.
AB  - The objective of this study was to examine the mechanisms of estrogen receptor
      (ER) processing and replenishment in the uterus of ovariectomized rats after
      estradiol and progesterone treatment. Uterine ER binding activity, ER protein and
      ER mRNA were measured by receptor binding exchange assay, Western blot and slot
      blot, respectively. The regulation of ER levels in rat uterus by estradiol and
      progesterone was very dramatic. Changes in ER protein were faithfully reflected
      by changes in binding activity. Estradiol caused receptor "processing" within 4 h
      of administration followed by recovery or "replenishment" of ER levels to the
      initial level by 20 h. The term "processing" has previously been used to describe
      the loss of ER binding activity in the early phase of estradiol-action, but it
      was never clear whether the ligand binding site was inactivated by processing or
      if the receptor molecule actually disappeared. This study shows that receptor
      "processing" constitutes disappearance of receptor protein and the later
      "replenishment" phase represents new ER protein rather than recycling of
      "processed" receptor. Progesterone-action, on the other hand, influenced only the
      "replenishment" phase by blocking recovery of ER protein. ER mRNA was suppressed
      by estradiol at 8 h, after the receptor was "processed" and "replenishment"
      already initiated. Progesterone, on the other hand, did not alter the steady
      state level of the message. Other mechanisms, such as regulation of translation
      rate of existing mRNA and changes in the rate of degradation of ER proteins are
      more likely involved in acute regulation of ER by these ovarian steroid hormones.

PMID- 8274404
TI  - Interaction of antiandrogen-androgen receptor complexes with DNA and
      transcription activation.
AB  - Human androgen receptor (hAR) is a ligand-dependent transcription factor that
      mediates androgen-induced actions on target tissues. Transfection studies in
      receptor deficient monkey kidney cells CV-1 in culture examine the ability of
      dihydrotestosterone (DHT) and of the antiandrogens hydroxylflutamide (HO-FLU),
      cyproterone acetate (Cypro.A) and RU 23908-10 to stimulate or to inhibit the
      transcription activation of mouse mammary tumor virus-bacterial chloramphenicol
      acetyltransferase (MMTV-CAT). CV-1 cells cotransfected with wild type hAR (hAR1
      910) and MMTV-CAT, were treated with varying concentrations of DHT. DHT
      stimulated transcription activation of MMTV-CAT gene in a dose-dependent fashion.
      Cypro.A though only partially, also stimulated the transcription activation of
      MMTV-CAT. In the absence of steroids, HO-FLU induced the MMTV-CAT transcription
      in transfectants only 4% above the basal level. RU 23908-10 revealed the least
      agonistic activity at concentrations between 10 nM and 1 microM. Despite this,
      100- to 1000-fold molar excess of all antiandrogens inhibited the agonistic
      activity of 10 nM DHT in this system. Receptor binding assays confirmed that HO
      FLU, Cypro.A and RU 23908-10 competed with [3H]DHT for AR binding with hAR
      expressed in CV-1 cells. Western blot analysis using AR antipeptide antibodies
      raised in rabbits revealed the presence of two AR protein bands in extracts
      prepared from hAR1-910 transfected CV-1 cells. Incubation of labeled synthetic
      palindromic androgen responsive element (ARE) with the hAR containing CV-1 cell
      extracts followed by u.v. cross-linking demonstrated the specificity of AR-DNA
      interaction. Analysis by gel mobility shift assays showed that the interaction of
      AR-antiandrogen complexes with labeled ARE was specific.

PMID- 8274405
TI  - Differential impact of flanking sequences on estradiol- vs 4-hydroxytamoxifen
      liganded estrogen receptor binding to estrogen responsive element DNA.
AB  - The mechanism by which antiestrogens antagonize the ability of estrogen receptor
      (ER) to induce the transcription of estrogen-regulated genes is only partially
      understood. To examine the effect of estrogen responsive element (ERE)
      stereoalignment and flanking sequences on estradiol-liganded ER (E2-ER)-ERE and
      antiestrogen-liganded ER (4-hydroxytamoxifen-liganded ER or 4-OHT-ER)-ERE
      binding, several dimeric EREs, containing a perfect inverted repeat (5'
      GGTCAgagTGACC-3') but lacking the AT-rich flanking sequences typical of highly
      estrogen-responsive promoters, were cloned into a plasmid vector. The ERE centers
      of symmetry were spaced 1.5, 2.0, 3.0, 6.4 and 6.7 helical turns apart. E2-ER and
      4-OHT-ER binding to these constructs was specific and saturable, but orientation
      independent and, in contrast to our earlier work with E2-ER binding to AT-rich
      EREs, not cooperative. The affinity of E2-ER binding decreased as the distance
      between adjacent EREs was increased, suggesting that E2-ER binding to closely
      spaced EREs is more stable (Kd = 0.38, 0.58, 0.83, 1.23, and 0.96 nM,
      respectively, for the above spacings). In contrast, the affinity of 4-OHT-ER
      binding increased with increased ERE spacing (Kd = 2.90, 4.79, 1.39, 1.77, and
      0.92 nM, respectively). The presence of AT-rich sequences flanking the ERE
      increased the binding affinity of E2-ER and 4-OHT-ER, an increase reflected in
      slower dissociation rates of ER from these EREs. The AT-rich sequence also
      enhanced the binding capacity of E2-ER but not 4-OHT-ER. Since the binding
      capacity of 4-OHT-ER is identical with or without an AT-rich region, we suggest
      that flanking sequences are more important in stabilizing E2-ER binding and may
      be critical for cooperative binding to stereoaligned EREs.

PMID- 8274406
TI  - Effects of antiandrogens on transformation and transcription activation of wild
      type and mutated (LNCaP) androgen receptors.
AB  - LNCaP cells contain androgen receptors with a mutation in the steroid binding
      domain (Thr 868 changed to Ala) resulting in a changed hormone specificity. Both
      the wild-type and mutated androgen receptors were transfected into COS cells.
      Transcription activation was studied in cells co-transfected with an androgen
      sensitive reporter (CAT) gene. The wild-type androgen receptor was activated by
      the agonist R1881, but the antiandrogens did not enhance transcription apart from
      a partial agonistic effect at high concentrations of cyproterone acetate. The
      mutated androgen receptor was fully activated by R1881, cyproterone acetate and
      hydroxyflutamide, but not by ICI 176,334. Receptor transformation to a tight
      nuclear binding state was studied by preparation of detergent washed nuclei and
      Western blotting with a specific antibody against the androgen receptor. Nuclei
      of COS cells transfected with wild-type receptor retained the receptor when the
      cells had been treated with the agonist R1881, partially retained receptors when
      treated with antiandrogen cyproterone acetate, but did not retain receptor when
      treated with hydroxyflutamide or ICI 176,334. The cells transfected with the
      mutated receptor additionally retained nuclear receptors after treatment with
      hydroxyflutamide. We conclude that each one of the three antiandrogens tested
      displayed different characteristics with respect to its effect on transformation
      and transcription activation.

PMID- 8274407
TI  - Influence of gender and the endocrine environment on the distribution of androgen
      receptors in the lacrimal gland.
AB  - Androgens are known to regulate both the structure and function of lacrimal
      tissue in a variety of species. To explore the endocrine basis for this hormone
      action, the following study was designed to: (1) determine the cellular
      distribution of androgen receptors in the lacrimal gland; and (2) examine the
      influence of gender and the endocrine environment on the glandular content of
      these binding sites. Lacrimal glands were obtained from intact, castrated,
      hypophysectomized, diabetic or sham-operated male or female adult rats, mice or
      hamsters, as well as from orchiectomized rats exposed to placebo compounds or
      physiological levels of testosterone. The cellular location of androgen receptors
      was evaluated by utilizing an immunoperoxidase protocol, in which a purified
      rabbit polyclonal antibody to the rat androgen receptor was used as the first
      antibody. Our findings with lacrimal glands showed that: (1) androgen receptors
      are located almost exclusively in nuclei of epithelial cells; (2) the cellular
      distribution or intranuclear density of these binding sites is far more extensive
      in glands of males, as compared to females; (3) orchiectomy or hypophysectomy,
      but not sham-surgery or diabetes, lead to a dramatic reduction in the
      immunocytochemical expression of androgen receptors; and (4) testosterone
      administration to orchiectomized rats induces a marked increase in androgen
      receptor content, relative to that in placebo-exposed glands. Our results also
      reveal that a 10 kb androgen receptor mRNA exists in the rat lacrimal gland.
      Overall, these findings demonstrate that gender and the endocrine system may
      significantly influence the distribution of androgen binding sites in rat
      lacrimal tissue. Moreover, our results show that androgens up-regulate their own
      lacrimal gland receptors.

PMID- 8274408
TI  - Messenger RNA phenotyping for semi-quantitative comparison of glucocorticoid
      receptor transcript levels in the developing embryonic mouse palate.
AB  - A specific complex of glucocorticoid and receptor interacts with responsive genes
      in target tissues of developing palate and controls its morphogenesis. In order
      to examine developmental changes in glucocorticoid receptor gene expression
      during embryonic palate formation, variations in transcript levels have been
      determined using a simple semi-quantitative reverse transcription-polymerase
      chain reaction (PCR) procedure. Oligo (dT)16 was used as the primer for reverse
      transcription, and the amount of PCR product for glucocorticoid receptor was
      normalized against those for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and
      beta-actin. We found that either GAPDH or beta-actin were suitable internal
      standards, and that the mRNA levels of glucocorticoid receptor undergoes a
      significant decrease of 30% at the developmental stage of embryonic mouse palatal
      shelf re-orientation. Immunolocalization of the receptor demonstrated a
      significant change in the distribution pattern of glucocorticoid receptor during
      the re-orientation stage of secondary palate formation. Our present data suggest
      that developmental variations in glucocorticoid receptor level control
      morphogenetic events of secondary palate formation.

PMID- 8274410
TI  - Involvement of GABAB receptors in the regulation of the hypothalamo-pituitary
      adrenocortical (HPA) axis in rats.
AB  - Previous experiments have shown that the GABAB receptor agonist L-baclofen given
      subcutaneously to male rats significantly enhanced plasma concentrations of
      adrenocorticotropic hormone (ACTH) and the adrenocortical hormones corticosterone
      and aldosterone. The goal of the present study was to investigate whether the
      stimulatory effects on adrenocortical steroids elicited by L-baclofen in vivo
      could be reversed by the selective GABAB antagonist CGP 35 348. One hour before
      subcutaneous administration of 3 mg/kg L-baclofen, a dose of 600 mg/kg CGP 35 348
      or saline was administered intraperitoneally. The stimulatory effect of L
      baclofen on ACTH, corticosterone and aldosterone was significantly reduced by 60%
      after pretreatment with CGP 35 348. The GABAB antagonist CGP 35 348 by itself had
      no effect on ACTH or the adrenocortical hormones. These results indicate that
      GABAB receptors are involved in the L-baclofen-induced activation of the HPA axis
      in rats. In vitro, however, neither L-baclofen nor CGP 35 348 had any effects on
      corticosterone and aldosterone release from perifused adrenal cells. These
      results suggest that the participation of GABAB receptors in the activation of
      the HPA axis induced by L-baclofen in vivo does not occur at the level of the
      adrenal gland, and therefore must occur at the level of the pituitary or the
      brain.

PMID- 8274409
TI  - Androgen receptor gene mutations in human prostate cancer.
AB  - To investigate the structural abnormality of the androgen receptor (AR) in human
      prostate cancers, exons B-H encoding DNA- and hormone-binding domains were
      examined by single-strand conformation polymorphism analysis of polymerase chain
      reaction products using originally designed oligoprimers. Tissues from 7 cases of
      untreated stage B prostate cancer surgically removed and from 8 cases of
      endocrine therapy-resistant cancers obtained at autopsy were used in the study.
      Two different mutations were identified in exons D and H in the different cancer
      foci of the same cancer death patient. One mutation in exon D (at codon 701, Leu
      to His) was detected in the prostate, and the other in exon H (at codon 877, Thr
      to Ala) was found in metastatic tissues. In untreated cancer tissues and the
      other autopsy samples, no mutations were detected. The mutation in exon H was
      identical to that reported in LNCaP cells. These results indicate that AR gene
      mutations occur in relation to endocrine therapy-resistance, although the
      mutation was found in 1 out of 8 resistant cases (12.5%) at autopsy.

PMID- 8274411
TI  - Dual subcellular localization of the 3 beta-hydroxysteroid dehydrogenase
      isomerase: characterization of the mitochondrial enzyme in the bovine adrenal
      cortex.
AB  - The enzyme 3 beta-hydroxysteroid dehydrogenase isomerase (3 beta-HSD/I) is an
      essential step in the biosynthesis of steroid such as progesterone, mineralo- and
      gluco-corticoids, estrogens and androgens in steroidogenic tissues. It is
      considered to be mainly localized in microsomes; however, 3 beta-HSD/I activity
      has also been described to be associated with mitochondrial preparations. In this
      study, we examined the subcellular distribution of 3 beta-HSD/I in bovine
      adrenocortical tissue and we characterized the catalytic properties of the enzyme
      present in the various cell compartments. About 30% of the total 3 beta-HSD/I
      activity was found to remain tightly associated with the purified mitochondrial
      pellet. The 3 beta-HSD/I and 3-ketoreductase activities were found in microsomes
      as well as in mitochondria. The 3 beta-HSD/I associated with the mitochondrial
      fraction did not require addition of exogenous NAD+. When the pyridine nucleotide
      was reduced following addition of substrates of the tricarboxylic acids cycle,
      the mitochondrial 3 beta-HSD/I activity decreased, suggesting that the enzyme
      utilizes NAD+ available from the matrix space. By contrast, the microsomal enzyme
      was inactive in the absence of exogenous NAD+. Submitochondrial fractionation
      disclosed that 3 beta-HSD/I was associated (i) with the inner membrane and (ii)
      with a particulate fraction sedimenting in a density gradient between inner and
      outer membranes. This fraction was characterized as contact sites between the two
      membranes. 3 beta-HSD/I specific activity was much higher in this fraction than
      in the inner mitochondrial membrane. Altogether, these observations suggest that
      these mitochondrial intermembrane contact sites may represent a special
      organization of functional significance, facilitating both the access of
      cholesterol to the inner membrane where cytochrome P-450scc is located and the
      rapid transformation of its product, pregnenolone, to progesterone, through 3
      beta-HSD/I activity.

PMID- 8274412
TI  - Catecholestrogens are MCF-7 cell estrogen receptor agonists.
AB  - Catecholestrogens are important metabolites of estradiol and estrone in the
      human. Considerable interest has focused on the catecholestrogens 2-hydroxy- and
      4-hydroxyestradiol since they bind to the estrogen receptor with an affinity in
      the range of estradiol. Using the MCF-7 cell line, we analysed the capacity of
      purified catecholestrogens to transform the estrogen receptor into its high
      affinity nuclear binding form and to affect receptor-dependent processes such as
      proliferation and expression of the progesterone receptor (PR). Incubations with
      2-hydroxy- and 4-hydroxyestradiol at 10(-8) M for 1 h resulted in tight nuclear
      binding of the estrogen receptor. During treatment of the cells with
      catecholestrogens we obtained a marked increase in proliferation rate of 36 and
      76% for 2-hydroxy- and 4-hydroxyestradiol, respectively, relative to the
      inductive effect of estradiol (100%). The PR level, was slightly increased by
      treatment with 2-hydroxyestradiol (10%), whereas treatment with 4
      hydroxyestradiol increased the PR level at 28%, compared to estradiol (100%).
      From these results we conclude that the 2- and 4-hydroxylated derivatives of
      estradiol are active hormones and are able to initiate estrogen receptor mediated
      processes in MCF-7 cells.

PMID- 8274413
TI  - Influence of indole carbinols and growth hormone on the metabolism of 4
      androstenedione by rat liver microsomes.
AB  - The effect of indole-3-carbinol (IC), an anticarcinogen present in cruciferous
      vegetables, to alter the metabolism of 4-androstenedione (AD) by female rat liver
      microsomes was investigated and compared to that of its main gastric conversion
      product, diindolylmethane (DIM) as well as other specific cytochrome P450
      inducers. DIM was a more potent inducer of the hydroxylase which converts
      androsterone to its 6 beta-hydroxylated derivative 3 alpha, 6 beta-dihydroxy-5
      alpha-androstan-17-one (A) than IC after either oral or intraperitoneal
      administration and was also a better in vitro inhibitor. Isosafrole (ISF), which
      like IC and DIM, induces CYP1A2 as well as gestodene, were powerful inhibitors of
      the in vitro reaction. Naringenin produced only a weak inhibitory effect while 3
      methylcholanthrene was inactive. SKF-525A, a prototypic hydroxylase inhibitor, or
      17 beta-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androst-1-ene-3-one which
      inhibits steroid 5 alpha-reductase, also decreased the formation of A from AD by
      liver microsomes. The infusion of human growth hormone by osmotic minipump, which
      feminizes hepatic steroid metabolism, increased the ability of male rat liver
      microsomes to convert AD to A and to respond to induction by IC. The identity of
      A, the main polar derivative of AD, induced by IC, DIM and ISF, was tentatively
      assigned by a combination of GC-MS and results from metabolic studies with
      intermediates in the pathway leading to its formation. It is proposed that the
      protective role of indole carbinols against mammary carcinoma due to decreased
      formation of 16 alpha-hydroxyestrone from estrone may be further enhanced by the
      diminished availability of AD for aromatization to estrone.

PMID- 8274414
TI  - Reversal of sexual impotence in male patients with chronic obstructive pulmonary
      disease and hypoxemia with long-term oxygen therapy.
AB  - Erectile impotence is commonly encountered in male patients with respiratory
      failure and hypoxia. In this study, 42% of the patients experienced reversal of
      sexual impotence during long-term oxygen therapy (LTOT). We examine the
      association between sexual impotence, gonadal axis hormones, hypoxia, and oxygen
      therapy. Nineteen sexually impotent male patients eligible for LTOT (pO2 < 7.3
      kPa during stable disease) and with sexual impotence received oxygen therapy for
      1 month (n = 12) or 24 h (n = 7). pO2, LH, FSH, testosterone, and SHBG (sex
      hormone binding globulin) were monitored. Five of 12 patients receiving oxygen
      for 1 month regained sexual potency. The responders showed a significant increase
      in arterial pO2 and serum testosterone, and a decline in SHBG compared to non
      responders. None of the patients receiving oxygen for 24 h experienced reversal
      of sexual impotence, despite a significant increase in pO2. In these patients,
      serum testosterone did not increase significantly. Reversal of sexual impotence
      may be achieved in some patients with respiratory failure. The oxygen therapy
      must, however be administered for an adequate length of time.

PMID- 8274415
TI  - 18-Ethynyl-deoxycorticosterone inhibition of steroid production is different in
      freshly isolated compared to cultured calf zona glomerulosa cells.
AB  - The inhibiting effects of 18-ethynyl-deoxycorticosterone (18-E-DOC) as a
      mechanism-based inhibitor on the late-steps of the aldosterone biosynthetic
      pathway were examined in calf adrenal zona glomerulosa cells in primary culture
      and in freshly isolated calf zona glomerulosa cells. 18-E-DOC inhibited the
      stimulated secretion of aldosterone and 18-hydroxycorticosterone in a similar
      dose-response and time fashion. No significant differences were found between the
      inhibition in cultured and freshly isolated cells (Ki of 0.25 vs 0.26 microM)
      Corticosterone secretion stimulated by ACTH or angiotensin II was also cultured
      in freshly isolated zona glomerulosa and fasciculata cells, but was not inhibited
      in cultured calf adrenal cells. Cortisol secretion stimulated by ACTH was not
      inhibited by 18-E-DOC in cultured zona fasciculata adrenal cells, but was
      inhibited in freshly isolated zona fasciculata cells with a Ki of 48 microM. The
      secretion of 18-hydroxyDOC or 19-hydroxyDOC stimulated by ACTH was not inhibited
      by 18-E-DOC. The bovine adrenal has been reported to have cytochrome P-450 11
      beta-hydroxylases that can perform the various hydroxylations required for the
      synthesis of cortisol and aldosterone in the different areas of the adrenal. In
      other species a distinct 11 beta-hydroxylase which participates in the
      biosynthesis of aldosterone and is located in the zona glomerulosa has been
      described. These studies with the mechanism-based inhibitor, 18-E-DOC, suggest
      that the bovine adrenal functions in a manner very similar to that of other
      species and raises the possibility that a distinct 11 beta-hydroxylase with
      aldosterone synthase activity might be present, but has not been cloned as yet.

PMID- 8274416
TI  - Testosterone and progesterone metabolism in the human neuroblastoma cell line SH
      SY5Y.
AB  - The ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens
      and progesterone was studied by incubating the cells in the presence of labeled
      testosterone (T) or progesterone (P) to measure, respectively, the formation of
      dihydrotestosterone (DHT) or dihydroprogesterone (DHP) (5 alpha-reductase
      activity). The 3 alpha-hydroxysteroid dehydrogenase activity was studied by
      evaluating the conversion of labeled DHT into 5 alpha-androstan-3 alpha, 17 beta
      diol (3 alpha-diol). The results show that undifferentiated neuroblastoma cells
      possess a significant 5 alpha-reductase activity, as shown by the considerable
      conversion of T into DHT; moreover, this enzymatic activity seems to be
      significantly stimulated following cell differentiation induced by the phorbol
      ester TPA, but not after differentiation induced by retinoic acid (RA). The 5
      alpha-reductase(s) present in SH-SY5Y cells is also able to convert P into DHP.
      In undifferentiated cells, this conversion was about 8 times higher than that of
      T into DHT. Under the influences of TPA and RA, the formation of DHP followed the
      same pattern observed for the formation of DHT. SH-SY5Y cells also appear to
      possess the enzyme 3 alpha-hydroxysteroid dehydrogenase, since they are able to
      convert DHT into 3 alpha-diol. This enzymatic activity is not altered following
      TPA-induced differentiation and appears to be decreased following treatment with
      RA. It is suggested that the SH-SY5Y cell line may represent a useful "in vitro"
      model for the study of the mechanisms involved in the control of androgen and P
      metabolism in nervous cells.

PMID- 8274417
TI  - Changes of [3H]naloxone binding in oestrogen stimulated rat uterus.
AB  - Effects of a single dose of oestradiol (Oe) on [3H]naloxone (Nal) binding in
      ovariectomized rat uterus were studied. Specific [3H]Nal binding was assessed by
      saturation analysis in 800 g supernatants and pellets of uterine homogenates. Two
      binding sites with higher (Kd approximately 1 nM) and lower affinity (Kd
      approximately 15 nM) for Nal were observed, their binding capacities and
      affinities have changed after Oe treatment in a time-dependent manner. The high
      affinity binding sites, detected only in the cytoplasmic fraction, disappeared
      after 1 h and only became detectable again at 24 h after hormone treatment, the
      lower affinity binding sites, after an initial drop, slowly increased, peaking at
      the 9th hour of hormone injection. The competition experiments indicate the
      involvement of different opiate receptor subpopulations in Oe induced changes. In
      the nuclear fraction, the Bmax values started to increase at 15 h, reaching the
      highest level at 18 h. The Kd values of lower affinity sites, in both studied
      compartments, were increased, i.e. the affinity decreased in the second half of
      the examined period.

PMID- 8274418
TI  - Cortisol metabolism in vitro--III. Inhibition of microsomal 6 beta-hydroxylase
      and cytosolic 4-ene-reductase.
AB  - The in vitro metabolism of cortisol in human liver fractions is highly complex
      and variable. Cytosolic metabolism proceeds predominantly via A-ring reduction
      (to give 3 alpha,5 beta-tetrahydrocortisol; 3 alpha,5 beta-THF), while microsomal
      incubations generate upto 7 metabolites, including 6 beta-hydroxycortisol (6 beta
      OHF), and 6 beta-hydroxycortisone (6 beta-OHE), products of the cytochrome P450
      (CYP) 3A subfamily. The aim of the present study was, therefore, to examine two
      of the main enzymes involved in cortisol metabolism, namely, microsomal 6 beta
      hydroxylase and cytosolic 4-ene-reductase. In particular, we wished to assess the
      substrate specificity of these enzymes and identify compounds with inhibitory
      potential. Incubations for 30 min containing [3H]cortisol, potential inhibitors,
      microsomal or cytosolic protein (3 mg), and co-factors were followed by
      radiometric HPLC analysis. The Km value for 6 beta-OHF and 6 beta-OHE formation
      was 15.2 +/- 2.1 microM (mean +/- SD; n = 4) and the Vmax value 6.43 +/- 0.45
      pmol/min/mg microsomal protein. The most potent inhibitor of cortisol 6 beta
      hydroxylase was ketoconazole (Ki = 0.9 +/- 0.4 microM; n = 4), followed by
      gestodene (Ki = 5.6 +/- 0.6 microM) and cyclosporine (Ki = 6.8 +/- 1.4 microM).
      Both betamethasone and dexamethasone produced some inhibition (Ki = 31.3 and 54.5
      microM, respectively). However, substrates for CYP2C (tolbutamide), CYP2D
      (quinidine), and CYP1A (theophylline) were essentially non-inhibitory. The Km
      value for cortisol 4-ene-reductase was 26.5 +/- 11.2 microM (n = 4) and the Vmax
      value 107.7 +/- 46.0 pmol/min/mg cytosolic protein. The most potent inhibitors
      were androstendione (Ki = 17.8 +/- 3.3 microM) and gestodene (Ki = 23.8 +/- 3.8
      microM). Although both compounds have identical A-rings to cortisol, and undergo
      reduction, inhibition was non-competitive.

PMID- 8274419
TI  - Cortisol metabolism by human liver in vitro--IV. Metabolism of 9 alpha
      fluorocortisol by human liver microsomes and cytosol.
AB  - The oxidative and reductive biotransformations of 9 alpha-fluorocortisol
      (fluorocortisol) by human liver microsomes and cytosol have been characterized. 9
      alpha-Fluorination greatly simplified cortisol metabolism in microsomes:
      dehydrogenation of the 11 beta-hydroxyl group and A-ring (4-ene-5 beta and 3
      alpha-keto) reduction, the principle pathways, were completely blocked.
      Fluorocortisol was essentially metabolized by the remaining pathways, 20 beta
      reduction and 6 beta-hydroxylation. In cytosol, 20 beta-reduction replaced the A
      ring reduction of cortisol as the sole biotransformation. The major structure
      metabolism relationships of fluorocortisol in man, i.e. complete and extensive
      inhibition of 11 beta-dehydrogenation and 4-ene-5 beta-reduction, respectively,
      were attributed to hepatic enzyme systems. Their mechanistic basis is discussed
      with reference to the electronic and conformational changes induced by 9 alpha
      fluorination.

PMID- 8274420
TI  - Bromocriptine-induced inhibition of hydroxylase/lyase activity of adult rat
      Leydig cells.
AB  - The present in vitro studies using a suspension of Leydig cells from adult rat
      testis demonstrated that bromocriptine (BR, 2 x 10(-5)M) inhibits hCG-stimulated
      testosterone production (in the presence of submaximal and maximal doses of hCG),
      while basal production was unaffected. When the cells were exposed to 8-bromo
      cAMP either in the presence or absence of hCG, the inhibitory effect of BR was
      not reversed. In intact cells, BR inhibited conversion of progesterone and 17
      hydroxy-progesterone to testosterone while conversion of androstenedione was not
      affected. Incubation of homogenates of Leydig cells in the presence of limiting
      NADPH concentrations (< or = 0.1 mM) resulted in significant BR-induced
      inhibition of conversion of progesterone (10 microM) to testosterone, while in
      the presence of "high" concentrations of NADPH (> or = 0.5 mM) BR was without
      effect. Present results suggest that BR inhibits androgen production at the level
      of the microsomal enzymes 17 alpha-hydroxylase and/or 17,20-lyase. The inhibitory
      effect of BR using homogenates of Leydig cells was evident only in the presence
      of limiting NADPH concentrations that suggests a competitive-like pattern of
      inhibition, but mechanisms by which BR decreases activity of microsomal enzymes
      remain to be determined.

PMID- 8274421
TI  - Relevance of oestrone presentation to the specificity of the elicited antisera,
      as revealed by affinity separation.
AB  - Polyclonal antisera raised against two different azobenzoyl-oestrone derivatives
      were analysed to investigate both the latency/intensity relationship of the
      immune response and the influence of antigen presentation on the specificity of
      the antisera elicited. Elongation of the azo-bridge of the hapten
      ([p(carboxyphenyl)-azo]-1,3,5[10]- oestratrien-3 ol-17 one) with a short
      aliphatic chain (4-amino-n-butyric acid) resulted in a marginal increase in the
      antibody yield, without affecting the time required to attain the maximum titre.
      The increased flexibility and mobility of the extended azo-bridge was shown to
      result in the appearance of antisera which cross-reacted with oestrogens with D
      ring structures different to that of oestrone. Antiserum fractionation by
      affinity chromatography through a stationary phase exposing the carrier protein
      determinants, as modified by the addition of the coupling bridge and the phenol
      ring, resulted in a reduction in its specificity. These findings are discussed
      with regard to the phenomena underlying the specificity of a polyclonal
      antiserum.

PMID- 8274422
TI  - Chromatin structure modulates transcription factor binding to the mouse mammary
      tumor virus (MMTV) promoter.
AB  - The MMTV promoter contains a complex hormone responsive region (HRR) upstream of
      a binding site for the transcription factor nuclear factor I (NFI). Hormonal
      induction of MMTV expression requires the integrity of both the HRR and the NFI
      binding site. However, in vitro NFI acts as a basal transcription factor on the
      MMTV promoter that does not cooperate but rather competes with the hormone
      receptors in terms of binding to MMTV-DNA. Fragments that contain the HRR and the
      NFI binding site have been reconstituted into mononucleosomes. Steroid hormone
      receptors bind efficiently to these nucleosomes, NFI does not. Therefore it has
      been postulated that the chromatin structure may be responsible for the inability
      of NFI to bind to the chromosomally organized inactive MMTV promoter. In vivo
      DNaseI and methidium-propyl-EDTA-Fe(II) (MPE) digestion pattern indicate the
      presence of a nucleosome covering the HRR and the NFI binding site. Genomic
      footprinting shows that in vivo the rotational setting of the MMTV promoter DNA
      in this nucleosome is identical to that previously reported for reconstituted
      nucleosomes in which the major grooves of the NFI half palindromes are facing
      towards the histone octamer and appear not to be accessible to NFI. These results
      indicate that MMTV promoter sequences are determining nucleosome positioning in
      vivo and supports the concept that rotational positioning of DNA in this
      nucleosome constitutively represses the MMTV promoter.

PMID- 8274423
TI  - Are breast tumours resistant to tamoxifen also resistant to pure antioestrogens?
AB  - A substantial proportion of patients with breast cancer are treated with the
      antioestrogen tamoxifen. As with other endocrine therapies, clinical experience
      has shown that some tumours in which growth is initially attenuated by tamoxifen
      treatment become resistant to continued drug treatment and resume growth. The
      mechanisms underlying the development of tamoxifen resistance have yet to be
      described but represent an important focus of research with the aim of defining
      what other therapies might be effective following tamoxifen treatment. Secondly,
      an understanding of tamoxifen resistance might suggest means to develop more
      effective agents for primary treatment of the disease. The development of pure
      antioestrogens, for example ICI 164,384 and ICI 182,780, which differ
      pharmacologically from tamoxifen in being entirely free of oestrogen partial
      agonist activity, together with cell and animal models of tamoxifen resistant
      human breast cancer, has revealed one mechanism which might be of considerable
      clinical significance. Pure antioestrogens were shown to inhibit the
      proliferation of a greater proportion of tumor cells than tamoxifen in vitro, a
      differential effect that was attributed to the oestrogenic activity of tamoxifen.
      Subsequently, cell culture studies have shown that breast cancer cell lines
      selected for resistance to tamoxifen can still remain sensitive to the growth
      inhibitory action of pure antioestrogens. Similarly, the growth of human breast
      tumours in nude mice, which is initially attenuated by tamoxifen but then
      resumes, can be inhibited by pure antioestrogens. Both types of experiment are
      consistent with the view that tamoxifen resistance in these model systems is due
      to the oestrogenic action of tamoxifen. Thus, it can be predicted that in some
      patients whose tumours recur during tamoxifen therapy, a further response to pure
      antioestrogen treatment might occur. Studies to examine this hypothesis are
      currently being undertaken with ICI 182,780. One mechanism which might account
      for the experimental observations is an intrinsic heterogeneity amongst breast
      tumour cells in their response to tamoxifen, i.e. that there are at least two
      different populations of cells; one population which responds to tamoxifen as an
      antioestrogen and one which "reads" tamoxifen as an oestrogen. The growth
      advantage thus conferred on the latter population would lead to its predominance.
      If this is what actually happens in a proportion of human tumours, it can be
      argued that primary treatment of the tumour with a pure antioestrogen, rather
      than tamoxifen, would be preferred since a more complete and longer-lasting
      response would be predicted. Recent comparative studies with human breast tumours
      grown in nude mice support these predictions.

PMID- 8274424
TI  - Structure and function of the glucocorticoid receptor.
AB  - Glucocorticoids cause changes in the expression of target genes via interaction
      with an intracellular receptor protein, the glucocorticoid receptor. This signal
      transduction process can be divided into a number of steps, each of which
      represents a functional facet of the receptor protein. These steps include (i)
      receptor transformation to an active form resulting from specific interaction
      with glucocorticoid steroid hormones, (ii) homo-dimerization, (iii) DNA-binding
      to specific hormone response elements in the genome and (iv) modulation of the
      expression levels of linked genes. These aspects of glucocorticoid receptor
      function have been studied using a combination of tertiary structure
      determination, biochemical assays and a genetic approach using a yeast system to
      screen for mutant receptors that are altered in function. The results show that
      contacts involving both the DNA and steroid binding domains are involved in
      dimerization and high affinity DNA binding. Genetic experiments have illuminated
      the role of amino acids within the recognition helix of the DNA-binding domain in
      discriminating between cognate DNA response elements for the glucocorticoid
      receptor and closely related binding sites for other nuclear receptors.
      Squelching experiments suggest that the N-terminal transactivation domain of the
      receptor contacts components of the general transcriptional machinery that appear
      to be distinct from the TATA binding protein, TFIID, during transactivation of
      gene expression by the DNA-bound receptor.

PMID- 8274425
TI  - Direct effect of gonadotropins on decidualization of human endometrial stroma
      cells.
AB  - Decidualization of stromal cells isolated from proliferative human endometrium
      was achieved by adding to the culture medium human gonadotropins (FSH, FSH + LH,
      hCG). In addition to changes in the morphology of the stromal cells to the
      decidual phenotype, decidualization was evident from the expression of prolactin
      (PRL), demonstrated immunocytochemically, by Western blotting analysis, and by
      measuring its output into the medium through solid phase enzyme immunoassay.
      Gonadotropins also induced cAMP formation in the endometrial stromal cells under
      the same experimental conditions. This finding suggests that the mechanism by
      which gonadotropins promote decidualization of human endometrial stromal cells in
      vitro involves the introduction of cAMP, a compound that we have found to elicit
      the expression of PRL in this system. PRL is likely to be a key intermediate in
      the process of decidualization since it is by itself capable of inducing
      differentiation of the endometrial stromal cells to the decidual phenotype.
      Awareness of direct actions of gonadotropins on the endometrial cells and, in
      particular, of the decidualizing effects of FSH (Metrodin), FSH+LH (Pergonal) and
      hCG may contribute to the understanding of physiologic as well as
      pathophysiologic conditions relevant to endometrial functions and fertility.

PMID- 8274426
TI  - Mechanism of synergistic action of all-trans- or 9-cis-retinoic acid and
      interferons in breast cancer cells.
AB  - Combination of all-trans-retinoic acid (RA) with either interferon-alpha or 
      gamma resulted in a synergistic amplification of the anti-proliferative effect on
      cultured breast cancer cells. RA could be replaced by other biologically active
      retinoids. The synergism was also observed for the induction of 2'-5'
      oligoadenylate synthetase, an enzyme which is involved in anti-viral activity of
      interferons and possibly in growth regulation of tumor cells. Combination of RA
      with interferon-gamma increased the down-regulation of specific binding sites for
      [125I]interferon-gamma. On the other hand interferons had no effect on the
      cytoplasmic binding protein for RA. Comparing all-trans- with 9-cis-RA, the
      latter was more effective in inhibiting tumor cell growth and in inducing
      synergism with interferon-gamma. This would indicate that retinoic X receptors
      are more important in mediating these effects than the RA receptors (RARs). This
      assumption is also supported by the failure of Ro-415253, a specific RAR-alpha
      antagonist, to reduce the synergistic interaction of RA with interferon with
      respect to growth inhibition.

PMID- 8274427
TI  - Characterization of two point mutations in the androgen receptor gene of patients
      with perineoscrotal hypospadia.
AB  - Perineoscrotal hypospadia is a major sign of sexual ambiguity due to inadequate
      androgen action in genetic and gonadal males. In patients showing these symptoms
      we have detected two androgen receptor gene mutations. In consequence we
      characterized the properties of the mutant receptors with respect to hormone
      binding, transactivation and DNA-binding. An amino acid substitution alanine-596-
      >threonine in the D-box of the androgen receptor was detected in 3 and 2
      brothers, respectively. This mutant receptor, AR-thr596, bound ligand in a normal
      fashion. It showed a promoter-dependent defect of transactivation and was unable
      to induce transcription of a promoter containing one androgen responsive element
      but showed almost wild-type transactivation of a promoter containing two closely
      spaced androgen-responsive elements. The complex promoter of the human prostate
      specific antigen gene was induced with intermediate efficiency. In
      electrophoretic mobility shift assays AR-thr596 was unable to form a complex with
      oligonucleotides containing 1 or 2 androgen responsive elements, however its DNA
      binding activity was restored by an anti-androgen receptor antibody in the
      presence of ligand. A point mutation which caused substitution of serine-703 in
      the hormone-binding domain with glycine was detected in a new-born male with
      ambiguous genitalia. This mutant receptor, AR-gly703, showed a reduced ligand
      affinity. The total amount of specific androgen binding sites in genital
      fibroblasts of the patient was reduced. Transactivation activity of AR-gly703 was
      dependent on hormone concentration. It was inactive at low levels of androgens
      but was fully activated in the presence of high androgen concentrations. The
      nature of the promoter had no effect on transactivation properties of this mutant
      androgen receptor. Its DNA-binding activity in gel shift experiments was normal.

PMID- 8274428
TI  - Hormonal regulation of transforming growth factor beta-2 expression in human
      prostate cancer.
AB  - We have previously shown that a transforming factor-beta species (TGF beta) is a
      hormonally regulated negative growth factor in estrogen responsive MCF-7 human
      breast cancer cells. We now demonstrate that androgen withdrawal leads to a
      significant stimulation of TGF beta-2 mRNA in the androgen-responsive human
      prostate carcinoma cell line LNCaP. These data indicate that TGF beta-2 is a
      marker of (anti)androgen action in human prostate cancer in vitro. Based on these
      results we addressed the question of whether TGF beta-2 represented a marker of
      (anti)androgen action in prostate cancer in vivo: expression of TGF beta mRNA was
      determined by RNAase protection analysis in normal and malignant prostate tissue
      obtained from 9 prostate carcinoma patients without endocrine therapy. In
      parallel, the nuclear dihydrotestosterone (DHT) concentration was measured as an
      indicator of androgen stimulation in the same tissues. The following results were
      obtained. Both normal and cancerous tissues show nuclear accumulation of DHT
      indicating a functional androgen receptor system. TGF beta-2 is equally expressed
      in both normal and cancerous tissue. Expression of TGF beta-2 and nuclear DHT
      concentrations are correlated in both benign and malignant tissue. We conclude
      that TGF beta-2 is a marker of (anti)hormonal action in androgen-dependent
      tissue.

PMID- 8274429
TI  - Estradiol regulation of secretory component: expression by rat uterine epithelial
      cells.
AB  - Sex hormones are known to play an important role in the regulation of mucosal
      immunity in the female reproductive tract. The purpose of this study was to
      examine the effect of estradiol (E2) on secretory component (SC) expression by
      epithelial cells in the rat uterus and to determine whether SC mRNA is present in
      uterine tissues and is under hormonal control. When ovariectomized rats treated
      with E2 for 3 days and sacrificed 12 h after the last injection, expression of SC
      on luminal and glandular epithelial cells, as determined by immunohistochemistry,
      was elevated when compared to control animals. To determine whether E2 regulation
      of SC involves mRNA synthesis, uterine RNA was extracted and analyzed by Northern
      blot. These experiments demonstrated that SC RNA is present in uteri from intact
      rats and markedly increased when ovariectomized animals are treated with E2. In
      other studies, uterine epithelial cells from adult rats were isolated and grown
      on permeable membranes for 5 to 10 days. Under these conditions, isolated
      epithelial cells grow to confluence, form tight junctions, and preferentially
      secrete SC into the apical medium. These studies identify epithelial cells as a
      key target cell in the uterus for the regulation of mucosal immunity by E2, which
      we postulate will play an important role in studies to prevent and/or control the
      spread of sexually transmitted diseases.

PMID- 8274430
TI  - Regulation of expression of the 3 beta-hydroxysteroid dehydrogenases of human
      placenta and fetal adrenal.
AB  - The appropriate expression of 3 beta-hydroxysteroid dehydrogenase/delta 5-->4
      isomerase (3 beta-HSD) is vital for mammalian reproduction, fetal growth and life
      maintenance. Several isoforms of 3 beta-HSD, the products of separate genes, have
      been identified in various species including man. Current investigations are
      targeted toward defining the processes that regulate the levels of specific
      isoforms in various steroidogenic tissues of man. High levels of expression of 3
      beta-HSD were observed in placental tissues. It has been generally considered
      that the multinucleated syncytiotrophoblastic cells are the principal sites of 3
      beta-HSD expression and, moreover, that 3 beta-HSD expression is intimately
      associated with cyclic AMP-promoted formation of syncytia. Herein we report the
      presence of 3 beta-HSD immunoreactive and mRNA species in uninucleate
      cytotrophoblasts in the chorion laeve, similar to that in syncytia but not
      cytotrophoblast placenta. In vitro, 3 beta-HSD levels in chorion laeve
      cytotrophoblasts were not increased with time nor after treatment with adenylate
      cyclase activators, whereas villous cytotrophoblasts spontaneously demonstrated
      progressive, increased 3 beta-HSD expression. Moreover, 3 beta-HSD synthesis
      appeared to precede morphologic syncytial formation. Thus high steroidogenic
      enzyme expression in placenta is not necessarily closely linked to formation of
      syncytia. Both Western immunoblot and enzymic activity analyses also indicated
      that the 3 beta-HSD expressed in these cytotrophoblastic populations was the 3
      beta-HSD type I gene product (M(r), 45K) and not 3 beta-HSD type II (M(r), 44K)
      expressed in fetal testis. In cultures of fetal zone and definitive zone cell of
      human fetal adrenal, 3 beta-HSD expression was not detected until ACTH was added.
      ACTH, likely acting in a cyclic AMP-dependent process, induced 3 beta-HSD type II
      activity and mRNA expression. The higher level of 3 beta-HSD mRNA in definitive
      zone compared with fetal zone cells was associated with parallel increases in
      cortisol secretion relative to dehydroepiandrosterone sulfate formation.

PMID- 8274431
TI  - The role of estrogen in the feedback regulation of follicle-stimulating hormone
      secretion in the female rat.
AB  - Letrozole (CGS 20267) is a non-steroidal aromatase inhibitor which, at its
      maximally effective dose of 1 mg/kg p.o., elicits endocrine effects equivalent to
      those seen after ovariectomy. Adult, female cyclic rats were administered
      letrozole (1 mg/kg p.o.) once daily for 14 days. A control group of animals was
      ovariectomized on day 1 of treatment and a third group of animals served as
      untreated controls. During the experiment, vaginal smears were taken daily and at
      the end of 14 days all animals were sacrificed, trunk blood was taken for serum
      estradiol, LH and FSH measurements and the uterus and ovaries were removed and
      weighed. The ovaries were then fixed and prepared for histological examination.
      Serum hormone measurements showed that after treatment with letrozole, serum
      estradiol levels were reduced by 76% of untreated controls and serum LH was
      elevated to 378% of control values. These compared favorably with those seen
      after ovariectomy, serum estradiol was reduced by 78% and serum LH was elevated
      to 485% of untreated controls. However, FSH was unchanged after letrozole
      treatment (125% of control), whereas after ovariectomy FSH rose to 398% of
      control. Uterine weight was suppressed in the letrozole-treated animals as well
      as the ovariectomized animals by 60 and 70%, respectively. The histology of the
      ovaries of animals treated with letrozole were consistent with the serum hormone
      findings. Except for the effects on serum FSH, these results confirm previous
      findings that treatment with letrozole elicits endocrine effects similar to those
      seen after ovariectomy. Furthermore, these results demonstrate that FSH secretion
      is not under the control of estradiol whereas LH secretion is under feedback
      control of ovarian estrogen.

PMID- 8274432
TI  - Sterol carrier protein 2: a role in steroid hormone synthesis?
AB  - The intracellular movement of cholesterol is an important regulated step in the
      process of steroidogenesis. However, the molecular mechanisms by which
      cholesterol is translocated to key organelles, including the mitochondria,
      remains poorly understood. Lipid transfer proteins may have an important function
      in this process. One candidate lipid transfer protein is sterol carrier protein 2
      (SCP2). This 13.2 kDa protein enhances the movement of cholesterol between
      vesicles and isolated mitochondria. It also stimulates mitochondrial pregnenolone
      synthesis. When introduced into intact cells, anti-SCP2 antibodies reduce steroid
      secretion. Moreover, expression of SCP2 in COS cells engineered to produce
      progestins increases steroid formation. SCP2 is abundant in steroidogenic glands
      and the pattern of SCP2 gene expression is consistent with a role for the protein
      in hormone synthesis: SCP2 transcripts are more prominent in the most
      steroidogenic compartments of the ovary and tropic hormones that stimulate
      steroidogenesis increase SCP2 gene expression. Other evidence that suggests that
      SCP2 plays important roles in cellular function includes a remarkable
      conservation of primary structure across species. The mechanisms by which SCP2
      promotes intracellular sterol movement have not been elucidated. The protein
      appears to bind sterols and is synthesized with a 20 amino acid N-terminal "pro-"
      sequence that may serve to target SCP2 to mitochondria. In addition, the C
      terminus of SCP2 contains a peroxisome-targeting sequence. SCP2 is derived from a
      large gene that encodes transcripts that are translated into larger proteins of
      30 and 58 kDa. The 58 kDa protein, which has some structural homologies with
      thiolases, seems to be specifically targeted to peroxisomes whereas SCP2 has a
      broader subcellular distribution. The significance of the peroxisome association
      of SCP2 and steroidogenesis has not been disclosed. However, diseases of
      peroxisome function, including adrenoleukodystrophy and Zellweger syndrome, have
      notable deficits in steroid and bile acid metabolism, thus linking peroxisomes
      and steroidogenesis. SCP2 is deficient in fibroblasts of patients with these
      diseases.

PMID- 8274433
TI  - The ontogeny of gene expression of progestin receptors in the female rat brain.
AB  - The postnatal development of the progestin receptor (PR) system in the rat brain
      is a region-specific and stage-related process. In an attempt to analyze the
      molecular mechanism by which the dramatic change of gene expression of the PR
      occurs we have examined the level of PR mRNAs in the hypothalamus-preoptic area
      (HPOA) and cerebral cortex in development from fetal to postnatal stages of
      female rats. We used polymerase chain reaction to clone, from uterine cDNA, the
      cDNA corresponding to the steroid-binding domain of the PR forms 'A' and 'B' mRNA
      as well as the region around the translation-initiation site (ATG1) of the
      putative PR form 'B' mRNA. A quantitative reverse transcription-polymerase chain
      reaction assay was used to measure the level of mRNAs for PR forms 'A' and 'B'
      (total PR mRNAs) and PR form 'B'. There was a regional difference in the
      intracerebral distribution between the total and form 'B' mRNAs, indicating
      possible distinct mechanisms responsible for regulating the expression of the PR
      mRNAs. The PR mRNAs in the brain, already detectable 2 days before birth,
      increased at early neonatal stages. The total PR mRNAs in the cortex developed in
      a manner essentially similar to the PR protein at the early stages, but,
      surprisingly, unlike the receptor, the messages remained high at the later stages
      from day 18 to 8 weeks of life. On the other hand, the ontogeny of the cortical
      mRNA for form 'B', which predominantly existed in the region, resembled that of
      the cortical PR protein. In the HPOA the postnatal development of the form 'B'
      mRNAs was also roughly similar to the PR. These results suggest region-specific
      and stage-related gene expression of the PR isoform system in the developing
      brain: gene expression of form 'B' seems to be predominantly, first, "turned on"
      around birth, followed by form 'A' mRNA expression around days 8-12. Moreover,
      lowered levels of the cortical PR mRNAs in the propylthiouracil-induced
      hypothyroid rat, together with suppressed PR level, indicate a possible
      regulatory role of thyroid hormone on gene expression of the cortical receptor.

PMID- 8274434
TI  - Brain mineralocorticoid receptor diversity: functional implications.
AB  - Mineralocorticoid receptors (MRs) in neurons of the anterior hypothalamus and the
      periventricular brain regions mediate aldosterone-selective actions on sodium
      homeostasis, salt appetite and cardiovascular regulation. Corticosterone is not
      effective in these neurons, possibly because it is enzymatically inactivated.
      However, MRs in limbic brain regions, notably in the hippocampal neurons, do
      already respond to very low concentrations of both corticosterone and
      aldosterone. The MR-mediated effects stabilize neuronal transmission and appear
      critical for neuronal integrity of a sub-region of the hippocampus: the dentate
      gyrus. Higher concentrations of corticosterone induced by stress and the
      circadian rise progressively activate the lower affinity glucocorticoid receptors
      (GRs), which in coordination with MR-mediated actions then facilitate adaptive
      processes required for recovery of homeostasis. It is postulated that this
      balanced MR- and GR-mediated action of corticosterone is of critical importance
      for regulation of the stress response and behavioural adaptation.

PMID- 8274435
TI  - Regulation of cytochrome P450 in the central nervous system.
AB  - The role of brain P450 in the physiology, pharmacology and toxicology of the
      brain is the subject of this study. Cytochrome P450 was isolated from the brains
      of rats and quantitated spectrally. The contribution of the known hepatic forms
      of the enzyme to the forms constitutive in the brain as well as those which are
      induced by hormones are xenobiotics were characterized on Western blots. We have
      found that the level of P450 in the brain is increased during pregnancy and
      lactation, by partial hepatectomy and by ethanol. In each case the profile of
      P450s induced is different. In pregnancy and lactation the P450 content of the
      hypothalamic preoptic area and olfactory lobes were increased up to 10-fold and
      the only subfamily identified on Western blots was 4A. There was no detectable
      1A, 2A, 2B, 2C, or 2E1. Ethanol increases the level of brain P450 3- to 5-fold
      and P450 2C, 2E1 and 4A are induced. Upon partial hepatectomy P450 1A, 2C and 4A
      were detected on Western blots but there was no 2E1. The inducibility of these
      forms of P450 in the brain suggests that there is in situ metabolism of steroids,
      fatty acids, prostaglandins, ethanol and other xenobiotics in the brain and
      raises questions about the role of brain P450 in the development of tolerance to
      drugs and the neurotoxicity of xenobiotics. More importantly, the action of
      neurotransmitters such as dopamine which utilize fatty acids metabolites as
      intracellular mediators, could be influenced by the levels of 2C and 4A P450s.

PMID- 8274436
TI  - Androgen and progesterone metabolism in the central and peripheral nervous
      system.
AB  - This paper summarizes the most recent data obtained in the authors' laboratory on
      the metabolism of testosterone and progesterone in neurons, in the glia, and in
      neuroblastoma cells. The activities of the 5 alpha-reductase (the enzyme that
      converts testosterone into dihydrotestosterone, DHT), and of the 3 alpha
      hydroxysteroid dehydrogenase (the enzyme that converts DHT into 5 alpha
      androstane-3 alpha, 17 beta-diol, 3 alpha-diol) have been first evaluated in
      primary cultures of neurons, oligodendrocytes and type-1 and -2 astrocytes,
      obtained from the fetal or neonatal rat brain. All the cultures were used on the
      fifth day. The formation of DHT of 3 alpha-diol was evaluated incubating the
      different cultures with labeled testosterone or DHT as substrates. The results
      obtained indicate that the formation of DHT takes place preferentially in
      neurons; however, type-2 astrocytes and oligodendrocytes also possess
      considerable 5 alpha-reductase activity, while type-1 astrocytes show a much
      lower enzymatic concentration. A completely different localization was observed
      for 3 alpha-hydroxysteroid dehydrogenase; the formation of 3 alpha-diol appears
      to be prevalently, if not exclusively, present in type-1 astrocytes; 3 alpha-diol
      is formed in very low yields by neurons, type-2 astrocytes and oligodendrocytes.
      The compartmentalization of two strictly correlated enzymes (5 alpha-reductase
      and 3 alpha-hydroxysteroid dehydrogenase) in separate central nervous system
      (CNS) cell populations suggests the simultaneous participation of neurons and
      glial cells in the 5 alpha-reductive metabolism of testosterone. Subsequently it
      has been shown that, similarly to what happens when testosterone is used as the
      substrate, the 5 alpha-reductase which metabolizes progesterone into 5 alpha
      pregnane-3,20-dione (DHP) shows a significantly higher activity in neurons than
      in glial cells; however, type-1 and -2 astrocytes as well as oligodendrocytes
      also possess some ability to 5 alpha-reduce progesterone. On the other hand, 3
      alpha-hydroxysteroid dehydrogenase, the enzyme which converts DHP into 5 alpha
      pregnane-3 alpha-ol-20-one, appears to be present mainly in type-1 astrocytes;
      much lower levels of this enzyme are present in neurons and in type-2 astrocytes.
      At variance with the previous results obtained using androgens as precursors,
      oligodendrocytes show considerable 3 alpha-hydroxysteroid dehydrogenase activity,
      even if this is statistically lower than that present in type-1 astrocytes. The
      existence of isoforms of the enzyme involved in androgen and progesterone
      metabolism is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8274437
TI  - The activated mammary gland specific nuclear factor (MGF) enhances in vitro
      transcription of the beta-casein gene promoter.
AB  - The hormonal induction of the beta-casein gene in mammary epithelial cells is
      dependent on the action of peptide and steroid hormones. Epidermal growth factor,
      insulin, glucocorticoids and prolactin act in a sequential manner to regulate the
      transcription of the gene. We have studied the hormonal requirements as well as
      the nuclear proteins which are involved in the induction process. In vitro
      transcription in cell free nuclear extracts has been used to demonstrate the
      central role of the mammary gland specific nuclear factor, MGF, in the mediation
      of the hormonal signals to the transcription machinery. A gene construct
      comprising 344 nucleotides of wild type beta-casein promoter sequence and a G
      free cassette of 220 nucleotides was used to test the activity of nuclear
      extracts in the in vitro transcription experiments. A construct in which the
      proximal MGF binding site in the beta-casein promoter region has been inactivated
      by mutation and a construct regulated by the adenovirus major late promoter
      served as controls. Nuclear extracts were prepared from Sf insect cells, HeLa
      cells and mammary epithelial cells of lactating rats. Strong transcription of the
      wild type beta-casein promoter construct was observed in the mammary cell
      extract, weak transcription in the extracts of Sf insect cells and the HeLa
      cells. The mutation of the MGF binding site drastically reduced the in vitro
      transcription in the mammary gland cell extract. Beta-casein promoter activity
      was also compared in nuclear extracts from uninduced and lactogenic hormone
      induced HC11 mammary epithelial cells. Extracts from induced cells are more
      efficient in the support of beta-casein gene transcription.

PMID- 8274438
TI  - Separate induction of the two isozymes of cytochrome P-450(11) beta in rat
      adrenal zona glomerulosa cells.
AB  - In the rat adrenal cortex, two isozymes of cytochrome P-450(11) beta (CYP11B1 and
      CYP11B2) have been identified. They are encoded by two different genes with a
      homology much higher in their coding than in their 5'-flanking regions. CYP11B1
      is found in all the zones of the gland and catalyzes a single hydroxylation of
      deoxycorticosterone (DOC) in the 11 beta- or the 18-position. CYP11B2 is produced
      exclusively in the zona glomerulosa and catalyzes all three reactions involved in
      the conversion of DOC to aldosterone. In vivo and in vitro, the expression of the
      genes encoding CYP11B1 and CYP11B2 is regulated by two separate control systems
      which appear to operate both independently and interdependently. In vivo zona
      glomerulosa expression of CYP11B1 was enhanced by ACTH treatment or potassium
      depletion and was lowered by potassium repletion. CYP11B2 expression disappeared
      upon potassium depletion or ACTH treatment, but reappeared during potassium
      repletion. In vitro, only CYP11B1 activity was detectable and responsive to ACTH
      treatment in zona glomerulosa cells cultured at a potassium concentration of 6.4
      mmol/l. Aldosterone biosynthetic activity and mRNA encoding CYP11B2 could be
      detected only after at least 1 day of exposure to a high extracellular potassium
      concentration (> or = 12 mmol/l).

PMID- 8274439
TI  - Glucocorticoid receptors: ATP-dependent cycling and hormone-dependent
      hyperphosphorylation.
AB  - The dependence of hormone binding to glucocorticoid receptors (GRs) on cellular
      ATP levels led us to propose that GRs normally traverse an ATP-dependent cycle,
      possibly involving receptor phosphorylation, and that without ATP they accumulate
      in a form that cannot bind hormone. We identified such a form, the null receptor,
      in ATP-depleted cells. GRs are basally phosphorylated, and become
      hyperphosphorylated after treatment with hormone (but not RU486). In mouse
      receptors we have identified 7 phosphorylated sites, all in the N-terminal
      domain. Most are on serines and lie within a transactivation region. The time
      course of hormone-induced hyperphosphorylation indicates that the primary
      substrates for hyperphosphorylation are the activated receptors; unliganded and
      hormone-liganded nonactivated receptors become hyperphosphorylated more slowly.
      After dissociation of substrates for hyperphosphorylation are the activated
      receptors; unliganded and hormone-liganded nonactivated receptors become
      hyperphosphorylated more slowly. After dissociation of hormone, most receptors
      appear to be recycled and reutilized in hyperphosphorylated form. From these and
      related observations, we have concluded that the postulated ATP-dependent cycle
      can be accounted for by hormone-induced or spontaneous dissociation of receptor
      Hsp90 complexes, followed by reassociation of unliganded receptors with Hsp90 via
      an ATP-dependent reaction like that demonstrated in cell-free systems. Other
      steroid hormone receptors might traverse a similar cycle. Four of the 7
      phosphorylated sites in the N-terminal domain are in consensus sequences for
      p34cdc2 kinases important in cell cycle regulation. This observation, along with
      the known cell cycle-dependence of sensitivity to glucocorticoids and other
      evidence, point to a role for receptor phosphorylation in controlling responses
      to glucocorticoids through the cell cycle.

PMID- 8274440
TI  - Hormone binding and transcription activation by estrogen receptors: analyses
      using mammalian and yeast systems.
AB  - We have used affinity labeling, site-directed mutagenesis and regional chemical
      mutagenesis in order to determine regions of the human estrogen receptor (ER)
      important in hormone binding, ligand discrimination between estrogens and
      antiestrogens, and transcriptional activation. Affinity labeling studies with the
      antiestrogen, tamoxifen aziridine and the estrogen, ketononestrol aziridine have
      identified cysteine 530 in the ER hormone binding domain as the primary site of
      labeling. In the absence of a cysteine at 530 (i.e. C530 mutant), C381 becomes
      the site of estrogen-compatible tamoxifen aziridine labeling. Hence these two
      residues, although far apart in the primary linear sequence of the ER protein,
      must be close in the three-dimensional structure of the protein, in the ER ligand
      binding pocket, so that the ligand can reach either site. Site-directed
      mutagenesis of selected residues in the ER and region-specific chemical
      mutagenesis of the ER hormone binding domain with initial phenotypic screening in
      yeast have enabled the identification of a region near C530 important in
      discrimination between estrogens and antiestrogens and of other residues
      important in hormone-dependent transcriptional activation. Some ER mutants with
      alterations in the carboxy-terminal portion of the hormone binding domain are
      transcriptionally inactive yet bind hormone and also function as potent dominant
      negative ERs, suppressing the activity of wild-type ER at low concentrations.
      These studies reveal a separation of the hormone binding and transcription
      activation functions of the ER. They are also beginning to provide a more
      detailed picture of the ER hormone binding domain and amino acids important in
      ligand binding and discrimination between different categories of agonist and
      antagonist ligands. Such information will be important in the design of maximally
      effective antiestrogens. In addition, since there is now substantial evidence for
      a mixture of wild-type and variant ERs in breast cancers, our studies should
      provide insight about the bioactivities of these variant receptors and their
      roles in modulating the activity of wild type ER, and should lead to a better
      understanding of the possible role of variant receptors in altered response or
      resistance to antiestrogen and endocrine therapy in breast cancer. In addition,
      some dominant negative receptors may prove useful in examining ER mechanisms of
      action and in suppressing the estrogen-dependent growth of breast cancer cells.

PMID- 8274441
TI  - Expression of the mouse glucocorticoid receptor and its role during development.
AB  - Genes encoding enzymes involved in gluconeogenesis are activated in liver shortly
      after birth by the synergistic effect of glucagon and glucocorticoids. This
      induction is achieved by the synergistic action of hormone responsive and liver
      specific enhancer elements. In the case of glucocorticoids, this enhancer is
      composed of a glucocorticoid-response element (GRE) and a number of cell-specific
      hepatocyte nuclear factor 3 (HNF-3) binding sites. The GRE binds the ligand
      activated glucocorticoid receptor (GR) which is ubiquitously expressed and the
      HNF-3 element binds a cell-specific protein factor. To further understand the
      role of cell-specific glucocorticoid signalling in the perinatal period and
      earlier during development we have studied the expression of the mouse GR gene.
      The gene has been cloned and fully characterized. Expression of the gene is
      controlled by at least three promoters, one of which is only active in T
      lymphocytes. Expression of GR mRNA has been detected back to day 9.5 of mouse
      development. The role of GR during mouse development has been further analysed by
      disruption of the GR gene in vivo by homologous recombination in mouse embryonic
      stem cells.

PMID- 8274442
TI  - Glucocorticoid receptor conversion to high affinity nuclear binding and
      transcription enhancement activity in Chinese hamster ovary cells subjected to
      heat and chemical stress.
AB  - The untransformed glucocorticoid receptor (GR) is a heteromeric complex
      containing two molecules of the 90-kDa heat shock protein (hsp90) and one
      molecule of the 56-kDa heat shock protein (hsp56). In the absence of hormone,
      this complex is found in the cytosolic fraction of cells, and upon hormone
      binding the complex dissociates and the GR is recovered in the nuclear pellet
      fraction. Given the association of heat shock proteins with the cytosolic form of
      the GR, we have examined the effects of heat shock on GR subcellular localization
      and transcription enhancement activity in a series of Chinese hamster ovary (CHO)
      cells which express either low levels of endogenous GR (CHOd cells), high levels
      of the mouse GR (WCL2 cells), or high levels of mutated mouse GR unable to bind
      DNA (NB cells). It was found that heat shock treatment of WCL2 cells results in
      wild-type mouse GR that is recovered almost entirely within the nuclear pellet
      fraction, a response similar to that seen in hormone-treated cells. In contrast,
      heat shock treatment of NB cells results in complete loss of GR from the
      cytosolic fraction, but almost no shift of GR to the nuclear nuclear pellet.
      These results indicate that heat shock-mediated conversion to high-affinity
      nuclear binding by the wild-type GR requires a functional DNA-binding domain, and
      that heat shock will result in loss of GR to proteolysis in the absence of
      nuclear sequestration. Analysis of MMTV-CAT reporter gene expression in these
      cells revealed that heat or chemical shock, in comparison to hormone-treatment,
      results in a small induction of MMTV-CAT expression in the WCL2 cells, but not in
      the CHOd or NB cells. These results indicate that cellular stress can cause at
      least a partial induction of hormone-independent GR-mediated gene expression.

PMID- 8274443
TI  - Xenopus peroxisome proliferator activated receptors: genomic organization,
      response element recognition, heterodimer formation with retinoid X receptor and
      activation by fatty acids.
AB  - Peroxisome proliferator activated receptors are ligand activated transcription
      factors belonging to the nuclear hormone receptor superfamily. Three cDNAs
      encoding such receptors have been isolated from Xenopus laevis (xPPAR alpha,
      beta, and gamma). Furthermore, the gene coding for xPPAR beta has been cloned,
      thus being the first member of this subfamily whose genomic organization has been
      solved. Functionally, xPPAR alpha as well as its mouse and rat homologs are
      thought to play an important role in lipid metabolism due to their ability to
      activate transcription of a reporter gene through the promoter of the acyl-CoA
      oxidase (ACO) gene. ACO catalyzes the rate limiting step in the peroxisomal beta
      oxidation of fatty acids. Activation is achieved by the binding of xPPAR alpha on
      a regulatory element (DR1) found in the promoter region of this gene, xPPAR beta
      and gamma are also able to recognize the same type of element and are, as PPAR
      alpha, able to form heterodimers with retinoid X receptor. All three xPPARs
      appear to be activated by synthetic peroxisome proliferators as well as by
      naturally occurring fatty acids, suggesting that a common mode of action exists
      for all the members of this subfamily of nuclear hormone receptors.

PMID- 8274444
TI  - Glucocorticoid receptor binding sites in the promoter region of milk protein
      genes.
AB  - The action of glucocorticoids on the induction of the two milk protein genes beta
      casein and whey acidic protein (WAP) is delayed and appears to be indirect. The
      response requires a co-stimulation of cells with prolactin, is restricted to
      mammary epithelial cells and is dependent on cis-acting sequences localized in
      the promoter region of the two genes. We have searched for glucocorticoid
      receptor (GR) binding sites in these hormone response regions. In vitro DNaseI
      footprinting experiments were performed with a purified preparation of the GR
      from rat liver. The sequences between -231 and -7 and between -250 and -79 of
      mouse WAP and rat beta-casein gene promoter, respectively, were found to contain
      multiple sites which were protected from the attack of DNaseI by the GR
      preparation. The sites comprise sequence motifs related to the delayed secondary
      glucocorticoid response elements described (Chan et al., J. Biol. Chem. 266,
      22,634-22,644, 1991), which represent half sites of classical GR binding sites.
      In the WAP gene promoter, the motifs are arranged head to tail with irregular
      spacing. The GR binding sites are in close proximity or even overlap with the
      bindings sites for candidate factors involved in mammary cell specific gene
      expression. The results suggest a direct co-operation between GR and mammary cell
      specific transcription factors in mediating the expression of milk protein genes.

PMID- 8274445
TI  - Mechanisms for tamoxifen resistance in breast cancer: possible role of tamoxifen
      metabolism.
AB  - Potential mechanisms for tamoxifen resistance include loss or alteration in
      estrogen receptor or other transcription factors and altered tamoxifen
      pharmacology. Using an experimental model, we have previously demonstrated that
      one form of tamoxifen resistance is related to the acquired ability of tamoxifen
      to stimulate tumor growth. These tamoxifen-stimulated tumors contain a reduced
      tamoxifen concentration and an altered metabolite profile suggesting that
      accumulation of more estrogenic metabolites could explain this phenomenon.
      However, in vivo treatment of nude mice carrying tamoxifen-stimulated tumors with
      fixed ring non-isomerizable analogs, or other analogs resistant to conversion to
      metabolite E (a full estrogen), still resulted in tumor growth stimulation.
      Growth of these tamoxifen-stimulated tumors was inhibited by a pure steroidal
      antiestrogen, ICI 182,780, suggesting that this drug should be investigated in
      patients with tamoxifen resistance. These tamoxifen-stimulated tumors could be
      further stimulated by estrogen replenishment, and estrogen stimulation was
      blocked by tamoxifen, indicating that tamoxifen has both agonist and antagonist
      properties in these tumors. Our data suggest that although tamoxifen-stimulated
      tumors display a markedly altered metabolite profile, isomerization or metabolism
      of tamoxifen does not fully explain the development of tamoxifen-stimulated
      growth. The mechanisms by which tamoxifen acquires more potent in vivo agonist
      properties over time remains to be defined.

PMID- 8274446
TI  - Androgen-induced growth factor and its receptor: demonstration of the androgen
      induced autocrine loop in mouse mammary carcinoma cells.
AB  - SC-3 cells derived from mouse mammary carcinoma (Shionogi carcinoma 115) exhibit
      remarkable growth enhancement and cell morphology change in response to androgen
      stimuli. These events are mediated through an androgen-induced growth factor
      (AIGF). Amino acid sequence deduced from cDNA reveals that AIGF has 215 amino
      acids with a signal peptide and scattered regions homologous to fibroblast growth
      factor (FGF) family proteins. The biological ability of AIGF to stimulate SC-3
      cell growth is inhibited by heparin or suramin. More importantly, antisense
      oligodeoxynucleotide of AIGF can block androgen-induced growth of SC-3 cells.
      Upon synthesis under the control of androgen, AIGF is immediately secreted into
      the extracellular space without intracellular accumulation. At the early phase
      (18-24 h) of androgen stimulation, however, AIGF is mainly associated with the
      glycosaminoglycan on the cell surface or extracellular matrix. In addition,
      treatment of SC-3 cells with sulfation blocker (chlorate) or heparitinase results
      in the abolishment of their ability to respond to androgen or AIGF, indicating
      that heparan sulfate has important roles for condensing AIGF on or near the cell
      surface as well as potentiating the biological activity of AIGF. Then, AIGF can
      bind to the FGF receptor. Northern blot analysis and cDNA cloning indicate that
      SC-3 cells predominantly express the FGF receptor 1 with some altered amino acid
      sequences. Transfection of expression vectors of AIGF and this variant form of
      FGF receptor 1 into FGF receptor-negative myoblast cells (L 6 cells) confirms
      that a variant form of FGF receptor 1 is a receptor of AIGF. These results
      clearly demonstrate that an autocrine mechanism is operating in androgen-induced
      growth of SC-3 cells.

PMID- 8274447
TI  - Cyclin gene expression and growth control in normal and neoplastic human breast
      epithelium.
AB  - Recent advances in defining the molecular mechanisms of cell cycle control in
      eukaryotes provide a basis for better understanding the hormonal control of cell
      proliferation in normal and neoplastic breast epithelium. It is now clear that a
      number of critical steps in cell cycle progression are controlled by families of
      serine/threonine kinases, the cdks. These kinases are activated by interactions
      with various cyclin gene products which form the regulatory subunits of the
      kinase complexes. Several families of cyclins control cell cycle progression in
      G1 phase, cyclins C, D and E, or in S, G2 and mitosis, cyclins A and B. Recent
      studies have defined the expression and regulation of cyclin genes in normal
      breast epithelial cells and in breast cancer cell lines. Following growth arrest
      of T-47D breast cancer cells by serum deprivation restimulation with insulin
      results in sequential induction of cyclin genes. Cyclin D1 mRNA increases within
      1 h of mitogenic stimulation and is followed by increased expression of cyclins
      D3 and E in G1 phase, cyclin A in late G1/early S phase and cyclin B1 in G2.
      Similar results were observed following epidermal growth factor stimulation of
      normal breast epithelial cells. Other hormones--oestrogens and progestins--and
      growth factors--insulin-like growth factor-I and basic fibroblast growth factor-
      with actions in G1 were also investigated for their effects on G1 cyclin gene
      expression. In all cases there was an excellent correlation between the induction
      of cyclin D1 mRNA and subsequent entry into S phase. Furthermore, growth
      inhibition by antioestrogens and concurrent G1 arrest were preceded by an acute
      decrease in cyclin D1 gene expression. These observations suggest a likely role
      for cyclin D1 in mediating many of the known hormonal effects on cell
      proliferation in breast epithelial cells.

PMID- 8274448
TI  - Transformation-sensitive localization of alpha-protein kinase C at cell-cell
      contacts in rat renal proximal tubule epithelial cells.
AB  - Immunocytofluorescence studies were used to compare alpha-protein kinase C (PKC)
      localization in primary cultures of renal proximal tubule epithelial cells (RPTE)
      with E1A-immortalized and SV40-transformed derivatives. Both cytosolic and
      nuclear staining were apparent in all of the RPTE. In primary RPTE, Triton X-100
      insoluble alpha-PKC was also apparent and was concentrated in cell junctions.
      Cell junction alpha-PKC was diminished in E1A-immortalized and absent from SV40
      transformed RPTE, even though total cellular content was not decreased. These
      results emphasize that subcellular location may play an important role in
      regulating signal transduction through PKC-dependent pathways. Phorbol ester
      treatment induced cell membrane ruffling in primary RPTE, and alpha-PKC was
      redistributed to membrane ruffles. However, the redistributed alpha-PKC was
      Triton soluble and, therefore, was distinct from cell junction alpha-PKC. The
      loss of alpha-PKC from cell junctions in phorbol ester-treated and oncogene
      altered cells suggests that there are cellular determinants regulating alpha-PKC
      association with junctional complexes.

PMID- 8274449
TI  - Human lung cancer cell lines exhibit resistance to retinoic acid treatment.
AB  - Retinoic acid (RA) and nuclear retinoic acid receptors (RARs) have been
      implicated in a variety of human malignancies including lung cancer, and RA has
      been proposed as a chemopreventive agent for bronchogenic carcinoma. Normal human
      tracheobronchial epithelial cells show dramatic induction of RAR-beta mRNA and
      significant growth inhibition after RA treatment. In contrast, 17 of 22 small
      cell lung cancer (SCLC) and 9 of 15 non-SCLC lines treated with 1 microM RA
      showed no significant growth inhibition. Of interest, 5 SCLC lines with high
      levels of myc gene family expression related to c-, N-, or L-myc gene
      amplification exhibited growth inhibition (28-87%), whereas 2 non-SCLC lines
      actually showed growth stimulation after treatment with 1 microM RA. The lines
      varied greatly in their constitutive expression of RAR-beta mRNA, and 15 of 20
      SCLC and 8 of 15 non-SCLC lines failed to show RAR-beta mRNA induction after RA
      treatment. Six cell lines showed possible alterations in the coding region of RAR
      beta by complementary DNA (cDNA)/polymerase chain reaction (PCR) analysis using
      primers common to the RAR-beta1,2,3 isoforms, since other regions would undergo
      cDNA/PCR amplification whereas the DNA binding domain would not. Nonetheless, no
      abnormal band shift patterns in cDNA amplified by PCR were found by single strand
      conformation polymorphism analysis covering all 1344 base pairs of the RAR-beta
      open reading frame. Finally, no abnormalities in RAR-alpha gene structure or
      expression were identified by Southern and Northern blot analysis, including
      lines with cytogenetic abnormalities of 17q21. We conclude that abnormalities of
      the RAR-beta system are common in human lung cancer cell lines.

PMID- 8274450
TI  - p53 mutations in mouse mammary epithelial cells: instability in culture and
      discordant selection of mutations in vitro versus in vivo.
AB  - The phenotypes of p53 mutations found in human and murine tumors often are
      analyzed using a variety of transformation assays in vitro, but data have not
      been available to correlate in vitro effects with in vivo activities. We have
      assessed the effects of p53 mutations using mouse mammary epithelial cell lines
      which can be analyzed both in vitro and in vivo. Parental mammary epithelial cell
      lines (FSK series) injected into cleared mammary fat pads of syngeneic mice
      frequently give rise to preneoplastic lesions (HAN) which can be reestablished in
      culture (TM lines) to permit analysis of genetic changes important in the
      development of preneoplasia. Characterization of the FSK3 cell line revealed a
      cell population mixed with respect to p53 genotypes. One subpopulation of mutant
      (Ser233-234) p53-expressing cells was selected in a preneoplastic mammary
      outgrowth in vivo (TM3), whereas another minor population of mutant (Pro135) p53
      expressing cells was selected during culturing of FSK3 cells in vitro. When FSK3
      cells were subdivided and passaged in parallel in vitro, p53 genotypes continued
      to evolve and diverge. These findings reveal that selective pressures exerted on
      mammary epithelial cell populations in vivo are different from pressures present
      in vitro. Selective forces may vary from one cell culture environment to another.
      The growth advantage conferred by a specific p53 mutation appears to differ in
      vivo versus in vitro. We propose that caution should be exercised when attempting
      to correlate the effects of p53 mutations assayed in cell culture systems with
      the in situ phenotypes of mutant p53 in cancer.

PMID- 8274451
TI  - Identification of 21 novel human protein kinases, including 3 members of a family
      related to the cell cycle regulator nimA of Aspergillus nidulans.
AB  - The nimA gene encodes a protein-serine/threonine kinase that is required along
      with the p34cdc2 kinase for mitosis in Aspergillus nidulans. We have searched for
      human protein kinases that are related to the NIMA protein kinase using the
      polymerase chain reaction. Different pairs of degenerate oligonucleotides
      specific for conserved amino acid motifs in the catalytic domain of NIMA were
      used as primers in the polymerase chain reaction to amplify partial complementary
      DNAs (cDNAs) of protein kinases expressed in the promyelocytic leukemia cell line
      HL-60. Forty-one distinct cDNAs representing a broad spectrum of serine/threonine
      and tyrosine-specific protein kinases were identified, and the sequences for 21
      of these protein kinases were found to be unique. Three of these cDNAs represent
      a family of protein kinases whose members are related to NIMA and the murine nimA
      related protein kinase Nek1. We discuss the success of this polymerase chain
      reaction approach with respect to the use of multiple primer pairs, the influence
      of primer degeneracy, and the tolerance of cDNA amplification to mismatches
      between primers and template mRNA.

PMID- 8274452
TI  - Human papillomavirus-immortalized keratinocytes are resistant to the effects of
      retinoic acid on terminal differentiation.
AB  - In order to study how human papillomaviruses (HPVs) can alter normal epithelial
      cell differentiation, we looked at the response to retinoic acid (RA) of HPV
      immortalized keratinocytes grown on organotypic cultures. Ten- to 30-fold higher
      concentrations of RA were required to block terminal differentiation in these
      cultures when compared to organotypic cultures of control cells. This resistance
      to RA was associated with maintained expression of differentiation-specific
      markers and, for keratin K1, Northern analysis showed that K1 mRNA was also
      detectable at 30-fold higher concentrations of RA in HPV organotypic cultures
      when compared to controls. These differences were reproducible and characteristic
      of all HPV cell lines studied, including very early passage HPV16-containing cell
      lines, suggesting that expression of HPV genes leads to this phenotype.
      Expression of epithelia-specific components of the RA response pathway was also
      studied by Northern analysis. At all RA concentrations, there were no detectable
      differences in overall levels of retinoic acid receptor gamma or cytosolic RA
      binding protein II mRNA found. Retinoid X receptor alpha expression was also
      evaluated, and, in two of three HPV-immortalized cell lines, it was found to be 2
      to 3 times as abundant as in controls. Although this difference in retinoid X
      receptor alpha expression could contribute to RA resistance, the mechanism
      involved in producing this resistance could not be fully elucidated in these
      studies. However, resistance to the effects of RA on epithelial differentiation
      is demonstrated in organotypic cultures of HPV-containing cells, and it is shown
      that this is associated with maintenance of RNA and protein expression of
      differentiation-associated genes at abnormally high concentrations of RA.

PMID- 8274453
TI  - Immortal cell lines isolated from heart differentiate to an endothelial cell
      lineage in the presence of retinoic acid.
AB  - Previously, we isolated a single line of transgenic mice which develop an
      enlarged heart due to the expression of the immortalizing gene, polyomavirus
      large T antigen. Immortal cell lines were isolated from adult transgenic but not
      from nontransgenic hearts. All of the 24 cell lines expressed vimentin and
      fibronectin but not desmin or myosin heavy chain. We conclude that the cell lines
      are of non-muscle origin. Six cell lines were chosen for further study. All six
      cell lines demonstrate profound morphological and biochemical effects when
      incubated with 10(-4) M to 10(-7) M retinoic acid. The retinoic acid-treated cell
      lines showed arrested cellular proliferation and aligned to form rows and vesicle
      like structures. Cycloheximide inhibited these retinoic acid-induced changes,
      indicating a need for continued protein synthesis. Retinoic acid-treated, but not
      untreated, cells lost expression of vimentin and fibronectin, gained the ability
      to incorporate acetylated low density lipoprotein, and expressed Factor VIII
      related antigen. Retinoic acid did not induce expression of desmin or myosin
      heavy chain. Incubation of the cell lines with transforming growth factor beta 1,
      dimethyl sulfoxide, or phorbol esters had no biochemical or morphological effect.
      We conclude that these cell lines differentiate to an endothelial lineage in the
      presence of retinoic acid.

PMID- 8274454
TI  - Expression of the nontransmembrane tyrosine phosphatase gene erp during mouse
      organogenesis.
AB  - We have studied the expression of the nontransmembrane tyrosine phosphatase gene
      erp during mouse development using in situ hybridization analysis. The results
      show that during the early postimplantational stages of development, erp
      expression is observed only in maternally derived decidual cells surrounding the
      developing embryo. At day 10.5, erp is weakly expressed in the embryo in the
      neural tube, hind gut, and other embryonic structures. However, in 12.5-day
      embryos, erp is present in most organs, with the highest expression restricted to
      the developing neural system. During later development, at day 17.5, the levels
      of erp decline in some neural structures but remain high in others, like the
      dorsal root ganglia. High levels of erp expression are maintained in several
      parts of adult brain, such as cortical layers, thalamus, hypothalamus, and
      hippocampus. High levels of erp transcripts are also observed in the cerebellar
      cortex, in the Purkinje cell layer, and in the granular cell layer. In all
      tissues analyzed, the expression of erp corresponds to regions undergoing
      terminal cell differentiation and/or regions where cell proliferation has
      declined.

PMID- 8274455
TI  - Functional interaction of wild-type and mutant p53 transfected into human tumor
      cell lines carrying activated ras genes.
AB  - We have analyzed the antiproliferative activity of the p53 tumor suppressor gene
      in human tumor cell lines harboring activated ras genes. The levels of p53
      protein and incorporation of bromodeoxyuridine in transiently transfected cells
      were determined simultaneously by flow cytometry. The human HT1080 fibrosarcoma,
      EJ bladder carcinoma, and SW480 colon carcinoma cell lines were equally sensitive
      toward wild-type p53-mediated inhibition of DNA synthesis, independent of the
      state of the endogenous p53 protein. Overexpression of p53 genes mutated at amino
      acid codon 143 resulted in increased proliferation of SW480 cells, which have two
      mutated endogenous p53 alleles. To mimic the genetic constitution of an evolving
      tumor cell that has sustained a mutation in one p53 allele, we coexpressed both
      wild-type and mutant p53 genes controlled by strong viral promoters in HT1080
      cells. Transiently transfected cells showed a reduced bromodeoxyuridine uptake
      similar to cells into which only wild-type p53 had been introduced. The wild-type
      p53 gene is a dominant growth suppressor over the mutant in all three different
      cell lines analyzed. By immunoprecipitation with antibodies PAb 122, PAb 420, and
      PAb 1620, we demonstrate the presence of both the mutant and wild-type
      conformations of the p53 protein in the transfected cells.

PMID- 8274456
TI  - Regulation of platelet-derived growth factor A messenger RNA translation in
      differentiating F9 teratocarcinoma cells.
AB  - We have monitored production of platelet-derived growth factor (PDGF) in F9
      teratocarcinoma cells. We show that undifferentiated F9 cells express PDGF A mRNA
      and produce biologically active PDGF AA homodimers. When differentiation is
      induced by treatment with retinoic acid and cyclic AMP, the production of PDGF AA
      protein is terminated. Contrary to expectation, inhibition of PDGF synthesis is
      exerted at a posttranscriptional level. Both undifferentiated and differentiated
      (1 day) F9 cell cultures contain comparable amounts of PDGF A mRNA. However, this
      mRNA becomes dissociated from polysomes during F9 cell differentiation.

PMID- 8274457
TI  - Molecular evidence for a clonal relationship between lymphomatoid papulosis and
      Ki-1 positive large cell anaplastic lymphoma.
AB  - Currently, considerable controversy surrounds questions about the clonal
      evolution of lymphomas in patients with lymphomatoid papulosis. In order to
      analyze a possible clonal relationship between lesions of lymphomatoid papulosis
      and a Ki 1+ large cell anaplastic lymphoma in the same patient, a highly specific
      molecular probe for the malignant lymphoid clone of the large cell anaplastic
      lymphoma was developed. As a clone specific molecular marker, highly variable
      junctional sequences of rearranged T-cell receptor-gamma genes were used. An
      oligonucleotide primer complementary to these sequences was synthesized and,
      using the polymerase chain reaction, clone specific DNA was detected in all
      lesions of lymphomatoid papulosis of the patient. These results provide evidence
      for a clonal relationship between lesions of lymphomatoid papulosis and large
      cell anaplastic lymphoma developing in the same patient.

PMID- 8274458
TI  - Activated keratinocytes present bacterial-derived superantigens to T lymphocytes:
      relevance to psoriasis.
AB  - In the past, epidermal keratinocytes were felt to be primarily concerned with the
      barrier function of skin. During inflammatory and immune-mediated skin diseases,
      keratinocytes were only portrayed as being passive/inert targets for noxious
      agents produced by infiltrating leukocytes. This innocent bystander and/or 'brick
      and mortar' conceptualization of the keratinocyte must now be significantly
      modified to take into account the growing body of experimental in vitro and in
      vivo results that substantiate re-classification of keratinocytes as fully
      fledged members of the immune system (i.e. immunocytes). Because keratinocytes
      produce important primary cytokines, adhesion molecules, and mononuclear cell
      chemotactic factors; as well as functioning as accessory cells for resting T
      lymphocytes, they can initiate and perpetuate the inflammatory and immunological
      reactions in the skin which contribute to the pathobiology of psoriasis. This
      review will emphasize the dynamic contribution that epidermal keratinocytes make
      to cutaneous immunohomeostasis, with particular focus on the potential role of
      bacterial derived superantigens and their ability to stimulate resting T cell
      proliferation when presented by cytokine-activated keratinocytes.

PMID- 8274459
TI  - T-cell receptor gene rearrangement in cells infiltrating skin eruptions specific
      to adult T-cell leukemia.
AB  - We examined T-cell receptor gene rearrangement in skin lesions and peripheral
      blood from 6 patients with adult T-cell leukemia (ATL) using the Southern blot
      method and a c beta 1 probe. A rearrangement signal common to skin lesions of all
      6 patients was observed. One patient (Case 4) exhibited another rearrangement
      signal in the skin lesion and an identical signal was detected in the peripheral
      blood. This is the first report describing a specific pattern of T-cell receptor
      gene rearrangement in ATL. The signal obtained is assumed to represent receptors
      of T cells involved in surveillance of HTLV-I infected T cells.

PMID- 8274460
TI  - Histamine stimulates normal human melanocytes in vitro: one of the possible
      inducers of hyperpigmentation in urticaria pigmentosa.
AB  - Isolated normal human melanocytes became enlarged and more dendritic in
      association with an increase in the activity of tyrosinase and the amount of b
      locus protein when they were cultured with 0.1-10 microM histamine in vitro.
      However, histamine did not exert a proliferative effect on them. The stimulatory
      effect of histamine was observable even 6 h after starting the treatment. This
      stimulation seems not to be pharmacologically mediated through histamine
      receptors, because it was inhibited neither by pyrilamine, a histamine H-1
      antagonist, nor by cimetidine, a H-2 antagonist. Imidazole derivatives that are
      rapidly metabolized from histamine in vivo and in vitro also stimulated the
      melanocytes. We propose that high concentrations of histamine and its imidazole
      metabolites continuously produced in the lesions of urticaria pigmentosa are
      probable causative factors of its characteristic skin pigmentation.

PMID- 8274461
TI  - Nickel sulfate-specific suppressor T cells induced by nickel sulfate in drinking
      water.
AB  - Suppressor T cell function was studied in nickel sulfate (NiSO4) delayed type
      hypersensitivity (DTH). NiSO4 in drinking water administered orally to normal
      mice for 10 weeks elicited no significant footpad swelling. However, after
      drinking water for 7 weeks, suppression of footpad swelling response was not
      detected. Suppression of footpad swelling response was mediated by CD4-8+ T
      cells. However, these suppressor T cells did not overcome CD4+8- helper T cells
      by co-transfer to recipient mice. Unresponsiveness to NiSO4 by oral
      administration of antigen was due to suppressor T cells.

PMID- 8274462
TI  - The acute effects of ultraviolet-B radiation on c-myc and c-Ha ras expression in
      normal human epidermis.
AB  - It is well known that ultraviolet radiation (UVR) causes DNA damage due to the
      formation of photoproducts which result in the inhibition of DNA synthesis. It
      has been reported that DNA damage by physical agents such as UVR and chemical
      carcinogens induces alteration of certain gene expressions. Recently the
      transient induction of c-myc and c-Ha ras proto-oncogene expressions has been
      observed in a human keratinocyte cell line in vitro. The present study was
      designed to investigate whether the induction of these proto-oncogenes occurs in
      normal human epidermis after UVR in vivo and to relate these findings to DNA
      synthesis. C-myc and c-Ha ras transcripts were detected throughout human
      epidermis before and after UVR. C-myc expression increased significantly 5 h
      after two times the minimal erythema dose (2 x MED) of UVR, while DNA synthesis
      of the irradiated skin had recovered from the UVR-induced inhibition. The
      intensity of c-Ha ras expression remained unchanged at both 5 and 24 h after UVR.
      These results suggest that the c-myc gene plays an important role in the recovery
      of keratinocytes from acute damage following UVR.

PMID- 8274463
TI  - Gene expression of collagenase and stromelysin in skin fibroblasts derived from
      dystrophic epidermolysis bullosa.
AB  - We studied expression of collagenase gene and stromelysin gene in skin
      fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa
      (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Northern blot
      analyses revealed that collagenase gene expression was markedly increased in two
      of four RDEB cells, as compared with three normal control cells. Moreover,
      stromelysin gene expression was also markedly increased in two RDEB cells, as
      compared with normal controls. In contrast, collagenase and stromelysin gene
      expression levels in three DDEB cells did not show any significant difference
      from those of normal controls, except one cell line which showed mild increase of
      both collagenase and stromelysin mRNA. Quantitative estimates of collagenase mRNA
      (U/micrograms RNA) determined by slot blot hybridizations showed that those of
      RDEBs: 0.92-1.81 (mean 1.3 +/- 0.45); DDEBs: 0.18-0.73 (mean 0.60 +/- 0.37);
      normal controls: 0.26-0.93 (mean 0.64 +/- 0.34). Stromelysin mRNA levels showed
      that those of RDEBs: 1.75-6.62 (mean 4.06 +/- 2.00); DDEBs: 0.55-3.78 (mean 1.69
      +/- 1.81); normal controls: 1.27-2.08 (mean; 1.55 +/- 0.45). These data
      demonstrated that collagenase and stromelysin gene expression was increased in
      some, but not all, RDEB cell lines. Our data suggested that collagenase and/or
      stromelysin could play a certain role for blister formation in RDEB, coordinately
      or in a distinct manner.

PMID- 8274464
TI  - The effect of three serum basic proteins on the mass of lipids in normal and
      hyperapoB fibroblasts.
AB  - We studied whether serum basic proteins (BPs) produce abnormal changes in the
      mass of cellular lipids in fibroblasts from patients with
      hyperapobetalipoproteinemia (hyperapoB) and if inhibition or stimulation of
      protein kinase C affects these processes. In normal cells, BP I increased the
      mean mass of triglycerides about twofold, whereas there was significantly less
      stimulation in hyperapoB cells (P < .005). The increase in the mass of cell
      cholesteryl esters seen in normal cells with BP I was also significantly reduced
      in hyperapoB cells (P < .005). In contrast, BP II abnormally stimulated the mass
      of cell cholesteryl esters sixfold in hyperapoB cells (P < .005). BP I also
      stimulated the mass of total phospholipids about twofold in normal cells, an
      effect that was reduced by about one third in hyperapoB cells (P = .08). No
      abnormality was found in hyperapoB cells with BP III. H-7, an inhibitor of
      protein kinase C, decreased the effects of BP I and BP II in normal and hyperapoB
      cells. C:8, an analogue of diacylglycerol, activated protein kinase C and
      stimulated triglyceride formation in normal (fourfold) and hyperapoB (fivefold)
      cells in the absence of BP I. When added with C:8, BP I further increased
      triglyceride production 1.5-fold in normal cells but not in hyperapoB cells. Two
      cellular abnormalities in lipid metabolism in hyperapoB fibroblasts were found,
      one with BP I, another with BP II. Protein kinase C activity was not deficient in
      hyperapoB cells, and the defect(s) may occur at another, perhaps earlier, step in
      the pathway.

PMID- 8274465
TI  - Cholesterol-fed and casein-fed rabbit models of atherosclerosis. Part 2:
      Differing morphological severity of atherogenesis despite matched plasma
      cholesterol levels.
AB  - One-month-old male New Zealand White rabbits were fed either a cholesterol-free
      casein diet (n = 10) or low-level cholesterol-supplemented chow (n = 10) for 24
      weeks, during which total plasma cholesterol levels were matched. After perfusion
      fixation, aortic tissue samples were taken from six predetermined locations and
      embedded in epoxy resin for examination by light and electron microscopy. Frozen
      sections were also obtained for histochemical demonstration of collagen and
      elastin. Lesion morphology was classified in toluidine blue-stained, semithin
      epoxy sections as early fatty streaks (round foam cells with little intervening
      extracellular matrix); advanced fatty streaks (foam cells with extracellular
      lipid); fibrous plaques (spindle-shaped cells within extracellular matrix); or
      atheromatous lesions (presence of an atheromatous core). In representative
      specimens, electron microscopy showed that the ultrastructure of round foam cells
      was consistent with macrophage derivation, whereas most spindle-shaped cells were
      clearly smooth muscle cells. Fibrous plaques were more common in the distal than
      the proximal aorta. Lesions in the casein-fed animals were essentially equally
      distributed among the four morphological categories, whereas lesions in the
      cholesterol-fed rabbits were predominantly of the atheromatous type. Thus,
      cholesterol-fed rabbits had, in general, more advanced lesions than casein-fed
      rabbits with matched total plasma cholesterol levels. Moreover, the feeding of a
      low-level cholesterol diet (0.125% to 0.5% by weight) to rabbits for a relatively
      short time (6 months) led to the development of advanced lesions similar to those
      seen in humans.

PMID- 8274466
TI  - Glycosaminoglycan fractions from human arteries presenting diverse
      susceptibilities to atherosclerosis have different binding affinities to plasma
      LDL.
AB  - The topographic distribution of atherosclerotic lesions is influenced by
      biochemical factors intrinsic to the arterial wall. In the present work we have
      investigated whether the composition/chemical structure of glycosaminoglycans
      constitutes one of these factors. Normal human arteries were obtained at
      necropsy, and in order of decreasing susceptibility to atherosclerosis, consisted
      of the abdominal and thoracic aortas and the iliac and pulmonary arteries. The
      results showed similar concentrations of total glycosaminoglycan and collagen. Of
      the glycosaminoglycans known to interact with low-density lipoprotein (LDL),
      dermatan sulfate was present in all arteries in comparable concentrations, but
      the aortas had a 30% higher content of chondroitin 4/6-sulfate, which in turn was
      slightly enriched in 6-sulfated disaccharide units. LDL-affinity chromatography
      with dermatan sulfate+chondroitin 4/6-sulfate fractions demonstrated that
      increasing affinity to LDL matched an increasing susceptibility to
      atherosclerosis. Analysis of glycosaminoglycans in the eluates indicated a
      positive correlation between affinity to LDL and increasing molecular weight and
      the existence of a fraction of glycosaminoglycans of high affinity to LDL in the
      aortas only. These results suggest that arterial glycosaminoglycans participate
      in the multifactorial mechanisms that modulate the differential localization of
      atherosclerotic lesions.

PMID- 8274467
TI  - Polymorphonuclear leukocytes enhance release of growth factors by cultured
      endothelial cells.
AB  - Porcine aortic endothelial cells (PAECs) in culture constitutively secrete
      polypeptide (endothelium-derived) growth factors (EDGFs) into the surrounding
      medium. Incubation of PAECs with human peripheral blood polymorphonuclear
      leukocytes (PMNs) caused a significant increase in EDGF release as assessed by
      [3H]thymidine incorporation into BALB/c 3T3 mouse fibroblasts and cell
      proliferation assay. The effect was time dependent and correlated with the number
      of PMNs, reaching a maximum with a 1:1 PAEC to PMN ratio. Generation of mitogenic
      activity was prevented by cycloheximide, indicating a requirement for de novo
      protein synthesis. Antibody-mediated inhibition assays suggested that mitogenic
      activity was due to platelet-derived growth factor and basic fibroblast growth
      factor. When supernatant from N-formyl-methionyl-leucyl-phenylalanine-stimulated
      PMNs was substituted for PMNs during incubation with PAECs, powerful mitogenic
      activity was generated, indicating the involvement of soluble mediators. A role
      for free oxygen radicals was ruled out by experiments in which superoxide
      dismutase and catalase did not prevent the increase in mitogenic activity. By
      contrast, serine protease inhibitors such as soybean trypsin inhibitor, alpha 1
      antitrypsin, and eglin C reduced the PMN-stimulating activity by 70%, 80%, and
      100%, respectively. The possible involvement of cathepsin G and elastase was
      investigated. Cathepsin G and elastase, when substituted for PMNs, increased the
      release of EDGFs in a dose-dependent fashion, mimicking the effect of PMNs. These
      findings suggest a new role for leukocyte-vessel wall interactions in the
      proliferative feature of atherosclerosis.

PMID- 8274468
TI  - ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout
      the arterial tree.
AB  - Initial description of apolipoprotein (apo) E-deficient transgenic mice
      demonstrated the development of severe hypercholesterolemia due to probable
      delayed clearance of large atherogenic particles from the circulation.
      Examination of these mice demonstrated foam cell accumulation in the aortic root
      and pulmonary arteries by 10 weeks of age. In the present study, the animals were
      fed either chow or a high-fat, Western-type diet and examined at ages ranging
      from 6 to 40 weeks. Gross examination by dissection microscopy revealed a
      predilection for development of lesions in the aortic root, at the lesser
      curvature of the aortic arch, the principal branches of the aorta, and in the
      pulmonary and carotid arteries. Monocyte attachment to endothelial cells was
      observed by light and electron microscopic examination at 6 weeks, the earliest
      time point examined. Foam cell lesions developed as early as 8 weeks, and after
      15 weeks advanced lesions (fibrous plaques) were observed. The latter consisted
      of a fibrous cap containing smooth muscle cells surrounded by connective tissue
      matrix that covered a necrotic core with numerous foamy macrophages. Mice fed the
      Western-type diet generally had more advanced lesions than those fed a chow diet.
      The apoE-deficient mouse contains the entire spectrum of lesions observed during
      atherogenesis and is the first mouse model to develop lesions similar to those in
      humans. This model should provide numerous opportunities to study the
      pathogenesis and therapy of atherosclerosis in a small, genetically defined
      animal.

PMID- 8274469
TI  - Serum estrone concentrations and coronary artery disease in postmenopausal women.
AB  - Little is known about the relation between serum sex hormones and either coronary
      heart disease or the development of atherosclerosis in women. We measured serum
      estrone concentrations in 87 postmenopausal women (age, 50 to 81 years) who were
      admitted for diagnostic cardiac catheterization. None of the women were on
      estrogen replacement therapy. Cases (n = 62) were defined as those women who had
      > or = 1 coronary artery with > or = 50% occlusion. All control subjects (n = 25)
      had 0% to 24% occlusion of all coronary arteries. Estrone concentrations, as
      measured by a combination of extraction, column chromatography, and
      radioimmunoassay, showed little difference between cases and control subjects. A
      difference of 6 pg/mL in the estrone level was not associated with a
      significantly increased risk of coronary artery disease (odds ratio [OR], 1.85;
      95% confidence intervals [CI], 0.60, 5.2). Examination of mean estrone levels on
      the basis of the number of occluded vessels was also not significant. The primary
      predictors of coronary artery disease in this population were a history of
      diabetes (OR, 8.8; CI, 1.5, 51.4) and age (5-year increments; OR, 2.1; CI, 1.2,
      3.8). There was also some suggestion that women who reported higher lifetime
      physical activity levels were at a reduced risk for developing coronary artery
      disease (OR, 0.18; CI, 0.05, 0.65). These preliminary results do not support the
      hypothesis that serum estrogens are related to coronary artery disease in older
      women, but these findings need to be replicated in larger populations of older
      women.

PMID- 8274470
TI  - Atherosclerosis in mice lacking apo E. Evaluation of lesional development and
      progression.
AB  - Apolipoprotein E-deficient mice have spontaneous elevations of total plasma
      cholesterol and triglycerides and reduced high-density lipoprotein. The mice
      develop arterial lesions in a time-dependent manner. Lesional distribution was
      centered in the aortic sinus in young mice, and the lesions were widely
      distributed throughout the arterial tree in mice at 8 to 9 months of age. In
      young mice, subendothelial foam cell deposits were present in the aortic sinus
      adjacent to valve-attachment sites. By 5 months of age, foam cell deposits, free
      cholesterol, and admixed smooth muscle cells composed the developing
      atherosclerotic lesions. After 8 to 9 months of age, the arterial lesions showed
      increased complexity, and fibrous cap lesions were present. Transmission electron
      microscopy showed foam cells, smooth muscle cells (both contractile and synthetic
      varieties), cellular debris, and acicular cholesterol deposits within the
      plaques. By scanning electron microscopy, subendothelial collections of foam
      cells were present within the aortic sinus and ascending aorta. The results show
      that the complexity of the atherosclerotic lesions that develop in these apo E
      deficient-mice are similar to those described in other species and therefore
      represent an important model for studies of genetic and environmental influences
      on the atherosclerotic process.

PMID- 8274471
TI  - Anatomic barriers influence the distribution of in vivo gene transfer into the
      arterial wall. Modeling with microscopic tracer particles and verification with a
      recombinant adenoviral vector.
AB  - We evaluated the extent to which anatomic barriers to vector penetration might
      influence the distribution of successful in vivo gene transfer into the normal
      arterial wall. A double-balloon catheter technique with infusion pressures of 100
      to 400 mm Hg was used to infuse microscopic tracer particles of the size range of
      liposomes and viral vectors into normal elastic arteries of sheep. Localization
      of the tracer particles in tissue sections by light, fluorescence, and electron
      microscopy suggested that vector-sized particles were delivered to the intima by
      direct infusion and to the adventitia via the arterial vasa vasorum. Particles
      were virtually absent from the arterial media. To test the predictions made from
      the particle studies, we repeated the infusion protocol with high-titer
      adenoviral vectors. Gene transfer occurred at high levels in the intima and along
      the adventitial vasa vasorum but again was virtually absent within the media. The
      ability of medial smooth muscle cells to be transduced was established in
      separate experiments with a high-pressure (5 atm) porous balloon infusion
      catheter. We conclude that (1) the anatomy of the normal elastic arterial wall
      imposes significant limitations on the penetration of particles in the size range
      of most gene-transfer vectors and (2) the distribution of in vivo gene transfer
      with adenoviral vectors is correctly predicted by the distribution of inert
      tracer particles. These findings have important implications for the design of
      arterial gene-transfer and gene-therapy protocols.

PMID- 8274472
TI  - Probucol reduces the cellularity of aortic intimal thickening at anastomotic
      regions adjacent to prosthetic grafts in cholesterol-fed rabbits.
AB  - Intimal hyperplasia is a persistent problem after implantation of prosthetic
      grafts. Although the mechanisms underlying this hyperplastic response are
      unknown, it has been proposed that such responses may be due to chronic vascular
      injury similar to that of atherogenesis. Thus, the role of oxidation was explored
      using the potent antioxidant drug probucol. Adult New Zealand White rabbits fed a
      modestly (0.25%) cholesterol-enriched diet had a polytetrafluoroethylene
      prosthetic graft placed into the lower aorta. After the grafting procedure, a
      group of 11 rabbits was placed on the cholesterol-enriched diet supplemented with
      1% wt/wt probucol while a control group of 10 rabbits was placed on the
      cholesterol-enriched diet alone. The rabbits were maintained for a further 10
      weeks before histological examination of the area surrounding the graft. Although
      administration of probucol did not significantly alter the dimensions of lesions
      at the anastomotic sites, the drug promoted striking histological changes in the
      surrounding tissue. Both groups of rabbits had a similar intimal hyperplastic
      response of the aortic tissue surrounding the graft. The vascular lesions present
      in the perigraft region of the control group consisted of a normal-appearing
      media but a thickened intima. The thickened intima contained numerous smooth
      muscle cells in a network of extracellular matrix. Regions in the neointima that
      were rich in smooth muscle cells exhibited modest staining for proliferating cell
      nuclear antigen. A few macrophages were present in the control group as
      determined by immunostaining with the monoclonal antibody RAM-11. In contrast,
      administration of probucol led to a marked reduction in the presence of RAM-11
      staining macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274473
TI  - Hypercholesterolemic effect of dietary cholesterol in diets enriched in
      polyunsaturated and saturated fat. Dietary cholesterol, fat saturation, and
      plasma lipids.
AB  - Within the context of reduced-fat diets, the effects of incorporating a fat high
      in stearic acid and adding moderate amounts of dietary cholesterol were examined
      in 14 middle-aged and elderly women and men (range, 46 to 78 years) with low
      density lipoprotein cholesterol (LDL-C) concentrations > 130 mg/dL (range, 133 to
      219 mg/dL) at screening. The subjects consumed each of the five diets, which were
      as follows: (1) a baseline diet (35% fat with 13% saturated fatty acids [SFAs],
      12% monounsaturated fatty acids [MUFAs], and 8% polyunsaturated fatty acids
      [PUFAs], and 128 mg cholesterol/1000 kcal); (2) a reduced-fat diet, in which two
      thirds of the fat was provided as corn oil (corn oil-enriched diet: 29% fat with
      7% SFAs, 9% MUFAs, and 11% PUFAs and 85 mg cholesterol/1000 kcal), which met the
      National Cholesterol Education Program (NCEP) Step 2 guidelines; (3) a reduced
      fat diet, in which two thirds of the fat was provided as beef tallow (beef tallow
      enriched diet: 31% fat with 13% SFAs, 11% MUFAs, and 3% PUFAs and 109 mg
      cholesterol/1000 kcal); and two reduced-fat diets, one (4) enriched in corn oil
      and the other (5) enriched in beef tallow, to which moderate amounts of
      cholesterol in the form of egg yolk were incorporated (197 or 226 mg
      cholesterol/1000 kcal final cholesterol content in corn oil- or beef tallow
      enriched diets, respectively). All diets were isocaloric and all food and drink
      were provided by the metabolic kitchen. Reducing the fat content of the diet
      resulted in decreased concentrations of LDL-C and high-density lipoprotein
      cholesterol (HDL-C).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274474
TI  - Lack of association between sex hormones and Lp(a) concentrations in American and
      Finnish men.
AB  - Sex hormones may play a role in the determination of cardiovascular disease.
      Recently lipoprotein(a) (Lp[a]) has been recognized as a risk factor for coronary
      heart disease. Estrogens and anabolic steroids have been reported to alter Lp(a)
      levels, yet no data are available on the association between in vivo
      concentrations of sex hormones and Lp(a) concentrations. We examined the possible
      associations of sex hormone-binding globulin, total and free testosterone,
      estradiol, and dehydroepiandrosterone sulfate to Lp(a) concentrations in men in
      two population-based studies (San Antonio Heart Study [n = 178] and a Finnish
      study on the association between insulin resistance and atherosclerosis [n =
      87]). In neither study were sex hormones significantly related to Lp(a)
      concentrations. In addition, Lp(a) was significantly related to apolipoprotein(a)
      molecular weight (which was measured in the Finnish study only). These results
      were unchanged when Lp(a) concentrations were adjusted for apolipoprotein(a)
      molecular weight (a strong correlate of Lp[a] concentrations). We conclude that
      in vivo concentrations of sex hormones are unlikely to be associated with Lp(a)
      concentrations in men.

PMID- 8274475
TI  - Microvascular endothelial cell sodding of 1-mm expanded polytetrafluoroethylene
      vascular grafts.
AB  - The formation of an endothelial cell lining on the inner surface of polymeric
      grafts may reduce the inherent thrombogenicity of synthetic implants. Endothelial
      cell transplantation onto the luminal surface of grafts has been suggested as one
      method of creating new endothelial cell linings on grafts. The purpose of this
      study was to morphologically evaluate the very early events of healing (between 4
      and 14 days) of 1-mm-internal-diameter expanded polytetrafluoroethylene (ePTFE)
      grafts that were treated with autologous microvessel endothelial cells at the
      time of graft implantation. We evaluated the development of new intimal linings
      in microvascular endothelial cell-sodded 1-mm ePTFE vascular grafts and compared
      their healing characteristics with non-cell-treated grafts by using a rat aortic
      graft model. Endothelial cells were isolated from intraperitoneal fat pads of
      female rats and transplanted onto the grafts by using a pressure sodding method.
      One-centimeter-long grafts were immediately implanted as interpositional grafts
      in the aorta. Non-cell-treated grafts were also implanted. Grafts were explanted
      4, 7, and 14 days after implantation and were evaluated by light and scanning
      electron microscopy. Morphometric analysis of the graft surfaces revealed the
      cellular coverage in sodded grafts to be 93.7 +/- 8.7% and in nonsodded grafts,
      1.1 +/- 1.9%. Areas not covered by cells exhibited thrombus and bare graft. The
      luminal lining of cells exhibited morphological characteristics, indicating they
      were antithrombogenic, based on morphological criteria, and exhibited
      characteristics of endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274476
TI  - LDLs increase the exposure of fibrinogen binding sites on platelets and secretion
      of dense granules.
AB  - Because previous studies show that lipoproteins affect platelet aggregation, we
      studied the effect of low-density lipoprotein (LDL) and high-density lipoprotein
      (HDL) on the binding of fibrinogen, which mediates platelet-platelet contact.
      Neither LDL nor HDL induced 125I-fibrinogen binding at concentrations up to 2 g
      protein/L. In contrast, platelets stimulated with 10 mumol/L ADP bound 63 734 +/-
      2453 molecules of fibrinogen per platelet. A 5-minute preincubation with LDL (0.5
      to 2 g/L protein) induced a dose-dependent increase to 91 307 +/- 2164 molecules
      of fibrinogen per platelet at 1.5 g/L, which is in the range found after optimal
      stimulation with alpha-thrombin. The increased fibrinogen binding in the presence
      of LDL resulted in faster aggregation with a 16% increase in single platelet
      disappearance and a faster optical aggregation at 5 mumol/L ADP and 1.5 g
      protein/L LDL. Inhibition of prostaglandin G2/H2-thromboxane A2 formation with
      indomethacin (30 mumol/L) did not change the stimulation by LDL. In contrast,
      modification of lysine residues of LDL, which is known to prevent specific
      binding to platelets, completely abolished the effect of LDL. Under the same
      conditions HDL did not change fibrinogen binding or aggregation. LDL also
      enhanced alpha-thrombin-induced [14C]serotonin secretion, but this property was
      not affected by lysine modification of LDL. These data indicate that LDL enhances
      platelet aggregation by stimulating the mechanisms that control exposure of
      fibrinogen binding sites on the glycoprotein IIB/IIIA complex via a mechanism
      that differs from the effect of LDL on secretion.

PMID- 8274477
TI  - Oxidized LDL induces monocytic cell expression of interleukin-8, a chemokine with
      T-lymphocyte chemotactic activity.
AB  - T lymphocytes, macrophages, and oxidized low-density lipoprotein (Ox-LDL) are
      collocalized in early atherosclerotic lesions. Using a low-endotoxin in vitro
      system, we observed that Ox-LDL but not native LDL induced the production, by
      both freshly adherent human peripheral blood monocytes and human monocytic THP-1
      cells, of the alpha chemokine interleukin (IL)-8, a potent chemoattractant for T
      lymphocytes. Marked IL-8 induction by Ox-LDL did not require IL-1 beta generation
      in THP-1 cells. Ox-LDL-induced chemokine production was selective, as Ox-LDL did
      not stimulate the production by THP-1 cells of the T-lymphocyte chemotactic beta
      chemokine macrophage inflammatory protein (MIP)-1 alpha. IL-8 induction increased
      in proportion to the extent of oxidation of LDL as measured by the content of
      lipid oxidation end products. To identify potentially active components of Ox
      LDL, we tested malondialdehyde, an arachidonate-derived lipid oxidation product,
      and 9-hydroxyoctadecadienoic acid, an oxidation product of linoleate, the major
      polyunsaturated fatty acid in LDL, and observed that they induced IL-8 generation
      in the absence of Ox-LDL. Furthermore, when most free lipid oxidation products
      were removed from Ox-LDL by dialysis, some IL-8-inducing activity was released
      into the dialysate. However, the major IL-8-inducing activity was not dialyzable.
      To address the nature of the LDL particle modification required to induce IL-8,
      acetylated or malondialdehyde-treated native LDL particles were monitored for
      activity. Neither procedure rendered LDL capable of inducing IL-8. However,
      phospholipase A2-treated LDL induced THP-1 cell expression of IL-8.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8274478
TI  - Fibrinogen and factor VII in the prediction of coronary risk. Results from the
      PROCAM study in healthy men.
AB  - Coronary thrombosis is regarded as the final occlusive event in the progress of
      coronary heart disease (CHD). Disturbances of the hemostatic system may favor
      this process and thus may indicate increased risk of myocardial infarction.
      Coagulation and lipid factors were measured in 2116 healthy male participants of
      the Prospective Cardiovascular Munster (PROCAM) study. After 6 years of follow
      up, 82 coronary events (9 sudden cardiac deaths and 14 fatal and 59 nonfatal
      myocardial infarctions) were observed. The mean plasma fibrinogen levels of the
      event and nonevent groups differed by 0.25 g/L (2.88 [SD, 0.68] versus 2.63 [SD,
      0.63] g/L, respectively; P = .001). The incidence of coronary events in the upper
      tertile of the plasma fibrinogen distribution was 2.4-fold higher than in the
      lower tertile. By multiple logistic function analysis, plasma fibrinogen was
      found to be an independent risk indicator for CHD (P < .05). Individuals in the
      high serum low-density lipoprotein (LDL) cholesterol tertile who also showed high
      plasma fibrinogen concentrations had a 6.1-fold increase in coronary risk.
      Unexpectedly, individuals with low plasma fibrinogen had a low incidence of
      coronary events even when serum LDL cholesterol was high. The mean factor VIIc
      activities in the event and nonevent groups did not differ significantly (112.3%
      [SD, 19.9] versus 108.4% [SD, 21.6]; P = .09). There was, however, a trend toward
      higher factor VIIc values when only fatal events were taken into account. Thus,
      higher levels of plasma fibrinogen markedly increased the predictive power of
      high serum LDL cholesterol. Low plasma fibrinogen is associated with low coronary
      risk even when LDL is raised.

PMID- 8274479
TI  - Activation of coagulation factor VII during alimentary lipemia.
AB  - Dietary studies have established a connection between plasma lipoproteins and
      coagulation factor VII. The present study was undertaken to specifically examine
      whether factor VII is activated during alimentary lipemia and to investigate the
      relations of factor VII mass and activity state with fasting and postprandial
      lipoproteins and free fatty acids (FFAs). Factor VII levels were therefore
      determined in plasma samples taken before and after intake of a standardized,
      oral fat load of a mixed-meal type in 33 men (mean age +/- SD, 48.8 +/- 3.2
      years) with a previous myocardial infarction at a young age and 10 healthy, age
      matched control subjects. A panel of methods for factor VII determination was
      used to ensure that changes in all potentially existing forms of the factor
      during alimentary lipemia would be included. Substantial activation of factor VII
      was found to occur during alimentary lipemia, whereas the number of factor VII
      molecules remained constant or even appeared to decrease after the test meal.
      Activation of factor VII was more pronounced in control subjects than patients,
      and the proportion of activated factor VII molecules was higher in control
      subjects. Interestingly, factor VII activation, which correlated quantitatively
      with the degree of postprandial triglyceridemia, seemed to be related to FFA
      production during lipolysis of triglyceride-rich lipoproteins that were generated
      in response to fat intake. Postheparin plasma lipoprotein lipase activity was
      lower in patients, which could offer one explanation why factor VII activity was
      lower during alimentary lipemia in these subjects despite their exaggerated
      postprandial triglyceridemia. Thus, activation of coagulation factor VII during
      alimentary lipemia may result in a procoagulant state that is likely to promote
      the formation of a coronary thrombus in individuals with established coronary
      artery disease.

PMID- 8274480
TI  - Recombinant human macrophage colony-stimulating factor reduces plasma cholesterol
      and carrageenan granuloma foam cell formation in Watanabe heritable
      hyperlipidemic rabbits.
AB  - Previous studies have demonstrated that short-term administration of recombinant
      human macrophage colony-stimulating factor (rhM-CSF) reduces plasma cholesterol
      in rabbits, nonhuman primates, and human subjects. This study extended the dose
      schedule of rhM-CSF to 8 weeks of continuous intravenous infusion (CIV) in the
      Watanabe heritable hyperlipidemic (WHHL) rabbit and expanded the scope to include
      an assessment of macrophage-derived foam cell development. Ten male WHHL rabbits
      were injected subcutaneously with 1% carrageenan to promote formation of a
      macrophage-rich foam cell granuloma. Rabbits were infused with either vehicle or
      rhM-CSF at 100 micrograms/kg per day (weeks 1 through 5) followed by 300
      micrograms/kg per day (weeks 6 through 8). rhM-CSF (100 micrograms/kg per day)
      decreased total plasma cholesterol by 45% at 2 weeks compared with controls. The
      gradual return of plasma cholesterol toward control concentrations over the
      subsequent 3 weeks correlated with the appearance of circulating antibodies
      specific to rhM-CSF. Granuloma weights at harvest (8 weeks after infusion) were
      significantly lower (2.8 +/- 0.7 g, mean +/- SEM) in rhM-CSF-treated rabbits
      relative to controls (7.1 +/- 1.5 g, P < .05). Granulomas from rabbits treated
      with rhM-CSF contained lower concentrations of cholesterol (2.0 +/- 0.7 versus
      6.1 +/- 1.5 micrograms/mg, P < .03) and cholesteryl ester (0.7 +/- 0.4 versus 3.9
      +/- 1.2 micrograms/mg, P < .03) than controls. Histological evaluation revealed
      that granulomas from the rhM-CSF-treated rabbits were more fibrous and contained
      fewer foam cells than those from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274481
TI  - Cytokines decrease apolipoprotein accumulation in medium from Hep G2 cells.
AB  - Cytokines, important biochemical mediators of inflammation, cause a rapid fall in
      the plasma concentration of cholesterol in vivo. One mechanism by which cytokines
      may cause acquired hypocholesterolemia is by decreasing the hepatic synthesis and
      secretion of apolipoproteins. To test this hypothesis, we incubated Hep G2 cells
      with human recombinant tumor necrosis factor-alpha, interleukin-1 beta, and
      interleukin-6. Each of the cytokines resulted in a dose-related reduction in the
      concentrations of apolipoprotein (apo) A-I, apoB, and lecithin:cholesterol
      acyltransferase (LCAT) activity in the medium after 24 hours of incubation. The
      effect of cytokines on apolipoprotein accumulation was not affected by
      preincubation of Hep G2 cells with fatty acids. Cytokines decreased the
      concentration of cellular apoA-I mRNA in a dose-related fashion but did not
      affect cellular concentrations of apoB mRNA. The concentrations of triglyceride
      and cholesterol were also reduced in the medium of cells incubated with
      cytokines. Total cell sterol synthesis rates were calculated by [14C]acetate
      incorporation. Cells incubated with interleukin-6 had a 31% increase in sterol
      synthesis rate but a 41% decrease in sterol secretion. These data suggest that
      these cytokines can decrease the hepatic synthesis and/or secretion of
      apolipoproteins and that this may explain, in part, the acquired
      hypocholesterolemia seen during acute and chronic inflammation.

PMID- 8274482
TI  - Cholesterol-fed and casein-fed rabbit models of atherosclerosis. Part 1:
      Differing lesion area and volume despite equal plasma cholesterol levels.
AB  - One-month-old male New Zealand White rabbits were fed either a cholesterol-free
      casein diet (CAS; n = 10); low-level cholesterol-supplemented (0.125% to 0.5% by
      weight) chow (CH; n = 10); or standard laboratory rabbit chow (n = 3) for 24
      weeks, during which total plasma cholesterol (TPC) levels were matched for the
      two experimental groups (TPCCAS = 475 +/- 39 mg/dL; TPCCH = 515 +/- 70 mg/dL).
      The percentage of cholesterol partitioned into each of the lipoprotein fractions
      except high-density lipoprotein (HDL) was significantly different for the
      experimental groups: casein-fed rabbits had a primarily low-density lipoprotein
      (LDL) hypercholesterolemia while cholesterol-fed rabbits had approximately equal
      levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein
      (IDL), and LDL cholesterol. Despite matched TPC, lesions in CH animals covered
      twice the luminal surface area (as detected by oil red O staining; P < .05) and
      had three times the total volume compared with lesions in the CAS group (P <
      .05). Lesion volume was positively correlated with TPC and IDL and LDL
      cholesterol for the CAS group and with TPC and IDL cholesterol for the CH group.
      When the experimental groups were combined, TPC and VLDL and IDL cholesterol were
      positively correlated with the lesion volume. Probability of occurrence maps
      revealed, however, that both groups were virtually identical with respect to the
      topographic distribution of lesions in the thoracic and abdominal aortas. The
      data suggested that the differential partitioning of cholesterol into the
      lipoprotein fractions seen in CAS and CH rabbits influenced lesion area and
      volume but not topographic distribution.

PMID- 8274483
TI  - Characterization of 5-fluorouracil loaded liposomes prepared by reverse-phase
      evaporation or freezing-thawing extrusion methods: study of drug release.
AB  - Entrapment of the anti-tumoral drug 5-fluorouracil (5-FU) in unilamellar
      liposomes prepared by freeze-thawing extrusion technique (FATVET) and the reverse
      phase evaporation method (REV) from natural (bovine brain) sphingomyelin (SM) and
      synthetic distearoylphosphatidylcholine (DSPC) phospholipids was studied. Reverse
      phase evaporation vesicles obtained from DSPC sized through polycarbonate
      membranes of 0.2 micron pore size were found to entrap roughly double amounts of
      drug than did extruded liposomes (0.1 micron pore size); however, s-REV in these
      preparations were more heterogenous in vesicle size than FATVET. The rate of in
      vitro drug release from the liposomes was found to be dependent of the bilayer
      composition and the method used to prepare the vesicles. The permeability
      coefficient P obtained was approx. 10(-11) m/s. The results suggest that 5-FU
      release is kinetically controlled by an interfacial process seemingly dependent
      on the surface activity of the drug. Also, the physical state of the bilayer
      determines the retention capacity of the vesicles. Thus, liposomes consisting of
      distearoylphosphatidylcholine whose acyl chains were in a gel state at the
      working temperature (37 degrees C) retained 70% of encapsulated 5-FU after 1 h,
      whereas liposomes composed of natural bovine brain sphingomyelin retained only
      15% over the same period.

PMID- 8274484
TI  - Absence of lipid gel-phase domains in seven mammalian cell lines and in four
      primary cell types.
AB  - Fluorescence properties of 6-lauroyl-2-dimethylaminonaphthalene (Laurdan) are
      used to explore gel and liquid-crystalline phase domains coexistence in membranes
      of various cell types and in erythrocyte ghosts. Experiments and simulations were
      performed using liposomes composed of equimolar gel and liquid-crystalline phases
      in the absence and in the presence of 30 mol% cholesterol. In this model system
      two distinct coexisting phases can be easily recognized in the absence of
      cholesterol. When cholesterol is added to this phospholipid mixture, Laurdan
      parameters characteristic of the gel and of the liquid-crystalline phase are no
      longer resolvable. Coexisting domains of gel and liquid-crystalline phase were
      not detected in any of the examined cell membranes as judged by Laurdan
      excitation and emission Generalized Polarization (GP) spectra. Both in liposomes
      and in cell membranes, the behaviour of GP values as a function of excitation and
      emission wavelength corresponds to a homogeneous liquid-crystalline phase,
      despite the absolute GP values being relatively high, closer to the values
      observed in gel phase phospholipids. The presence of cholesterol appears to be
      the major cause for the homogeneity of phospholipids' dynamical properties in
      natural membranes, properties that appear close to the liquid-ordered phase
      state, defined to describe model systems with cholesterol concentration > or = 30
      mol%.

PMID- 8274485
TI  - Amino acid substitutions in the membrane-binding domain of cytochrome b5 alter
      its membrane-binding properties.
AB  - The structure-function relationships of the 43-amino-acid membrane-binding domain
      of cytochrome b5 have been examined in two mutant forms of the protein. In one
      mutant, two tryptophans in the membrane-binding domain, at positions 108 and 112,
      were replaced by leucines, and in the second mutant, in addition, aspartic acid
      103 was also replaced by leucine. The fluorescence emission spectra of the three
      proteins and their degree of quenching by brominated lipids indicate that the
      mutations are not producing major conformational changes or allowing a deeper
      degree of penetration of the domain into the bilayer. The hydrophobicities of the
      three proteins were compared, by determining strengths of self-association and
      membrane affinities, and it was found that the protein with two additional
      leucines was much less hydrophobic and the one with three additional leucines was
      much more hydrophobic than the native cytochrome. It appears that small changes
      in amino acid composition, which produce no gross changes in the structure of the
      membrane-binding domain, will nevertheless produce very large changes in the
      strengths of self- and membrane-association. These differences in self
      association had profound effects on the times required for membrane-association
      to reach equilibrium.

PMID- 8274486
TI  - Kinetics of incorporation of porphyrins into small unilamellar vesicles.
AB  - The kinetics of hematoporphyrin or deuteroporphyrin incorporation in egg
      phosphatidylcholine small unilamellar vesicles have been investigated by
      fluorescence stopped-flow measurements. The processes can be described by a fast
      equilibrium. The on-rate constant is nearly diffusion controlled regardless of
      the compound used and the pH. The affinity of these porphyrins for the vesicles
      is merely governed by the exit rate which depends on the structure of the
      porphyrin and on its charge determined by pH.

PMID- 8274487
TI  - A membrane-bound form of protein disulfide isomerase (PDI) and the hepatic uptake
      of organic anions.
AB  - Protein disulfide isomerase (PDI) was considered to be involved in the hepatic
      uptake of certain organic anions because the protein is photoaffinity labeled by
      photolabile derivatives of the bile acid taurocholate. Several lines of evidences
      including photoaffinity labeling experiments indicated a close relationship
      between the uptake of bile acids and the organic anion bumetanide. The possible
      involvement of PDI in hepatic transport processes of these organic anions was
      tested with polyclonal antibodies raised against a PDI-beta-galactosidase fusion
      protein. Western blot analysis and immunofluorescence of intact hepatocytes
      showed that protein disulfide isomerase is located in sinusoidal rat liver plasma
      membranes. This protein is immunologically identical with microsomal PDI prepared
      from bovine liver. The plasma membrane form of PDI is, however, not labeled by
      photoactivated bumetanide as revealed by two-dimensional gel electrophoresis.
      These results indicate that, although a membrane-bound form of the PDI is present
      in the sinusoidal plasma membrane of rat hepatocytes, this protein is not
      involved in the hepatocellular uptake of the organic anion bumetanide.

PMID- 8274488
TI  - Rabbit skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase activity: stimulation
      in vitro by thyroid hormone analogues and bipyridines.
AB  - Sarcoplasmic reticulum-enriched membranes from rabbit skeletal muscle contained
      Ca(2+)-ATPase activity which was significantly enhanced (26% increase, P < 0.001)
      in vitro by physiological concentrations (10(-10) M) of L-thyroxine (T4) and
      3,3',5-triiodo-L-thyronine (T3). In contrast, the biologically inactive
      iodothyronine analogues D-T4 and 3,3',5,5'-tetraiodothyroacetic acid (Tetrac)
      (10(-10) M) were without effect on enzyme activity. 3,5-Dimethyl-3'-isopropyl-L
      thyronine (Dimit), a bioactive analogue, was highly effective as a Ca(2+)-ATPase
      stimulator, increasing enzyme activity by 43% (P < 0.02 vs. T4 effect). A
      bipyridine cardiac inotropic agent, milrinone, has been reported to be
      thyromimetic in a myocardial membrane Ca(2+)-ATPase system, and in concentrations
      from 10(-10) to 10(-5) M enhanced skeletal muscle SR membrane Ca(2+)-ATPase
      activity in vitro (P < 0.001). Milrinone analogues which have been previously
      shown to enhance rabbit myocardial membrane Ca(2+)-ATPase activity, and which
      have a twist relationship of the pyridine rings, were also striated muscle Ca(2+)
      ATPase stimulators. We conclude that (1) striated muscle is a mammalian tissue in
      which physiological levels of biologically relevant thyroid hormone analogues,
      particularly Dimit, stimulate Ca(2+)-ATPase activity in vitro by a non-genomic
      mechanism; (2) cardiac bipyridine analogues which are thyromimetic in vitro in
      rabbit heart, and which have structural homologies with thyroid hormone, are
      stimulators of rabbit striated muscle sarcoplasmic reticulum Ca(2+)-ATPase
      activity.

PMID- 8274489
TI  - Static and dynamic studies of the potential-sensitive membrane probe RH421 in
      dimyristoylphosphatidylcholine vesicles.
AB  - The dynamics of the potential-sensitive styryl dye RH421 in
      dimyristoylphosphatidylcholine vesicles have been investigated above and below
      the main phase transition temperature using iodine-laser temperature-jump
      relaxation spectrophotometry and time-resolved fluorescence lifetime
      measurements. Equilibrium fluorescence titrations have shown that the affinity of
      the dye for the membrane is much higher in the liquid-crystalline state than in
      the gel state. The interaction can be described by either a partition or a
      binding model and a theory is presented providing a relation between these two
      approaches. In the liquid-crystalline state bound dye exhibits steady-state
      fluorescence relaxation processes in the submicrosecond and millisecond time
      range following a temperature jump. Time-resolved fluorescence measurements show
      a variation in the fluorescence lifetime across the emission spectrum, suggesting
      an excited-state process occurring on the subnanosecond time scale. These
      processes are most likely related to dye and/or lipid reorientation following the
      temperature jump or excitation pulse. Temperature-dependent changes in the
      fluorescence excitation spectrum of bound dye suggest that the dye exists in at
      least two different sites within the membrane.

PMID- 8274490
TI  - Intracellular pH regulation in cecal epithelial cells from the chick.
AB  - Intracellular pH (pHi) regulation has been investigated in cells isolated from
      the proximal ceca of the chicken. pHi was measured with the pH-sensitive dye,
      2',7'-bis(carboxyethyl)-5 (6)-carboxyfluorescein in nominally HCO(3-)-free
      solutions. Under resting conditions the pHi was 7.08. Removal of extracellular
      Na+ decreased pHi by approx. 0.24 pH units and the subsequent addition of Na+
      increased pHi towards the control value. This Na(+)-dependent pHi recovery was
      inhibited by 5-(N-ethyl-N-isopropyl)amiloride (EIPA). Following an intracellular
      acidification, by abrupt withdrawal of NH4Cl, pHi alkalinized in the nominally
      absence of Na+. Rotenone, N-ethylmaleimide, N,N'-dicyclohexylcarbodiimide, 4
      chloro-7-nitrobenz-2-oxa-1,3-diazole, iodoacetic acid and SCH 28080 inhibited the
      Na(+)-independent pHi recovery rate by 82, 82, 67, 74, 77 and 50% respectively.
      Bafilomycin A1 was without effect. Na(+)-independent cell alkalization was
      stimulated by external K+. In the presence of N-ethylmaleimide addition of Na+
      induced a rapid pHi recovery. The initial rate of this recovery exhibited first
      order dependence on Na+ concentration and it was inhibited by EIPA. The initial
      rate of Na(+)-dependent cell alkalization increased with a Hill coefficient
      greater than one when pHi was reduced from 7.2 to 6.2. The 'set point' for the
      exchanger is approx. 7.5. These studies demonstrate that in cecal epithelial
      cells exist at least two mechanisms for proton secretion: a Na(+)-H+ exchanger
      and a Na(+)-independent proton transport system.

PMID- 8274491
TI  - Deregulation by zinc of the sodium efflux in barnacle muscle fibers.
AB  - Single muscle fibers from the barnacle Balanus nubilus were employed to study the
      behavior of the resting Na+ efflux toward external and internal application of
      zinc (Zn2+). This involved both unpoisoned and ouabain-poisoned fibers. The
      results obtained are as follows: (i) External application of Zn2+, e.g., 2 mM (a
      maximal dosage) in 10 mM Hepes-ASW (pH 7.3) causes a fall in the resting Na+
      efflux which exceeds that caused by 10(-4) M ouabain in companion controls. (ii)
      The buffer of choice is found to be Hepes, rather than HCO3- or imidazole. (iii)
      The observed fall in the resting Na+ efflux caused by external application of
      Zn2+ is concentration-dependent, the IC50 being 10 microM. (iv) The inhibitory
      effect of Zn2+ is partially reversible; occasionally, however, reversibility is
      not seen. (v) The Zn(2+)-insensitive component of the Na+ efflux is reduced by
      10(-4) M ouabain. (vi) The ouabain-insensitive component of the Na+ efflux is
      reduced by external application of Zn2+. This response is concentration
      dependent. (vii) Preinjection of EGTA reduces the sensitivity of the Na+ efflux
      to external application of Zn2+. This is true of both unpoisoned and ouabain
      poisoned fibers. (viii) (a) The resting Na+ efflux is reduced by injecting Zn2+.
      Ouabain application reduces the remaining Na+ efflux. (b) Injection of Zn2+
      reduces the ouabain-insensitive component of the Na+ efflux. (c) External
      application of Zn2+ following the injection of Zn2+ reduces the remaining Na+
      efflux. Ouabain is ineffective when applied after both maneuvers. (d) Injection
      of Zn2+ after its external application is without effect. Subsequent application
      of ouabain is also without effect. (e) Injection or external application of Zn2+
      reduces the ouabain-insensitive Na+ efflux. Whereas in the former case subsequent
      external application of Zn2+ reduces the remaining Na+ efflux, in the latter case
      Zn2+ injection after external application of Zn2+ is ineffective. Collectively,
      these results provide evidence in support of the hypothesis that Zn2+ is a potent
      inhibitor of the ouabain-sensitive and ouabain-insensitive components of the Na+
      efflux, and that the inhibitory effect is partly due to the entry of Zn2+ into
      the myoplasm. They also raise the possibility that the inhibitory effect caused
      by Zn2+ injection may be the result of Zn2+ leakage from the fiber interior.

PMID- 8274492
TI  - Transport of choline by Madin-Darby canine kidney cells.
AB  - Choline is an essential precursor for the synthesis of phosphatidylcholine, the
      most abundant phospholipid classes in renal cells, as well as for the synthesis
      of the osmolyte glycerophosphorylcholine. The characteristics of choline uptake
      in the renal epithelial cell line MDCK were investigated. In the range of
      physiological concentrations, choline entered MDCK cells, grown as a monolayer on
      solid support, via a specific sodium-independent transport system (apparent Km =
      43 microM, apparent Vmax = 284 pmol/mg protein per 5 min). Cell ATP depletion,
      addition of KCl to the medium to reduce the cell membrane potential, and
      hemicholinium-3 (HC-3) inhibited choline uptake. Specific binding of [3H]HC-3 was
      detected on the apical membrane of cells grown on plastic dishes, whereas it
      occurred only on the basolateral domain of cells grown on permeant support. When
      growing cells on filter, choline uptake from the basolateral side was 10-times
      the apical uptake. This suggests that the choline carrier present at the apical
      domain of cells grown on solid support is either inactivated or no longer
      targeted to the apical but to the basolateral membrane of MDCK cells grown on
      filter.

PMID- 8274493
TI  - Electrical impedance and erythrocyte sedimentation rate (ESR) of blood.
AB  - The electrical impedance of blood is primarily determined by plasma resistance
      Rp, cell interior resistance Ri, and cell membrane capacitance Cm. These
      impedance parameters were measured for 62 samples with various erythrocyte
      sedimentation rates (ESR = 1-150 mm/h). A formula for estimating ESR by Rp and Cm
      was obtained by linear regression as: In (ESR) = 10.16-0.016 x f0, (r = 0.974, P
      < 0.001), where f0 = 10(9)/(2 pi.Rp100.Cm100) defined as the effective
      characteristic frequency in kHz, Rp100 = Rp/h in omega cm, Cm100 = Cm/h in pF/cm,
      h is the haematocrit in decimal. The 95% confidence intervals for the
      coefficients in the above equation were 9.73 to 10.59 and -0.017 to -0.015. The
      origin of the association was found reasonable since factors increasing the ESR,
      i.e., the concentration of some plasma proteins and the size of the blood cells,
      also elevate the capacitance. The results imply that the impedance measurement
      might be an alternative method for fast determination of the ESR.

PMID- 8274494
TI  - A voltage-dependent and a voltage-independent potassium channel in brown
      adipocytes of the rat.
AB  - Single-channel recordings of a voltage-dependent potassium channel in brown
      adipocytes of the rat confirm recordings of macroscopic currents. Single-channel
      conductance (gamma) is 8 pS at 20 degrees C in KF solution inside vs. a modified
      Ringer's solution outside. With KCl solution outside, gamma is 17 pS for outward
      currents and 21 pS for inward currents. The majority of the channels inactivate
      with a time constant around 200 ms; deactivation occurs within milliseconds. The
      channel is blocked by tetraethylammonium (TEA) with an inhibiting constant of 1.8
      mM. The type of block is fast. Selectivity sequence for monovalent cations is K+
      > Rb+ >> NH4+ >> Li+ > or = Na+ approximately Cs+. Cs+ at the outside causes a
      voltage-dependent block of inward currents. This channel is remarkably similar to
      the delayed rectifier of the F-type in the node of Ranvier. Occasionally, an
      additional K+ channel was found. This channel is voltage-insensitive, not blocked
      by 10 mM TEA, and has not been recorded in brown adipocytes before. Physiological
      relevance of this channel could be the steady-state membrane potential.

PMID- 8274495
TI  - The membrane potential has no detectable effect on the phosphocholine headgroup
      conformation in large unilamellar phosphatidylcholine vesicles as determined by
      2H-NMR.
AB  - In this study the effect of a transmembrane electrical potential on the
      phospholipid headgroup conformation was investigated using the 2H-NMR technique.
      Large unilamellar vesicles were prepared of dioleoylphosphatidylcholine,
      specifically 2H-labeled at the alpha- or beta-position of the choline group. No
      conformational change of the phosphocholine headgroup could be detected after
      induction of a valinomycin-induced K(+)-diffusion potential across the bilayer.
      However, this method could be used to measure the redistribution of
      tetraphenylphosphonium across the bilayer in response to delta psi, which
      reorients the phosphocholine headgroups in the opposite bilayer-water interfaces.

PMID- 8274496
TI  - Determination of the intracellular free chloride concentration in rat brain
      synaptoneurosomes using a chloride-sensitive fluorescent indicator.
AB  - The chloride-sensitive fluorescent indicator MQAE (N-(6-methoxyquinolyl)
      acetoacetyl ester) has been used for determination of the intracellular free
      chloride concentration in rat brain synaptoneurosomes. Loading of the
      synaptoneurosomes with MQAE occurs by transmembrane diffusion. Calibration of the
      intracellular MQAE was done by determining the correlation between fluorescence
      intensity and intrasynaptoneurosomal Cl- concentration in the presence of the Cl
      /OH- exchanger tributyltin and the K+/H+ exchanger nigericin, starting from zero
      Cl- concentration. The total quenchable signal of MQAE was determined by adding
      KSCN in the presence of the K+ ionophore valinomycin. The correlation between the
      reciprocal of the fluorescence intensity and the chloride concentration was
      linear at least up to 50 mM Cl-. The fluorescence of freshly prepared
      synaptoneurosomes was then measured and the obtained value was plotted into the
      calibration curve and the corresponding Cl- was read. The mean
      intrasynaptoneurosomal chloride concentration was 14 +/- 4 mM. We also
      quantitatively estimated the Cl- flux after addition of the barbiturate,
      pentobarbitone that opens GABAA receptor-Cl(-)-channels, to the
      synaptoneurosomes. An addition of 1 mM pentobarbitone corresponded to an approx.
      0.59 mM change in the intrasynaptoneurosomal free chloride concentration. The
      results show that the chloride-sensitive fluorescent indicator MQAE is a useful
      tool when determining intracellular chloride activity, and in quantitative
      determination of chloride fluxes in living cells and subcellular preparations.

PMID- 8274497
TI  - Overexpression of the ER-membrane protein P-450 CYP52A3 mimics sec mutant
      characteristics in Saccharomyces cerevisiae.
AB  - High expression of microsomal cytochrome P-450 CYP52A3 from Candida maltosa
      induces the formation of membrane stacks in Saccharomyces cerevisiae. Membrane
      proliferation is accompanied by coinduction of the ER proteins KAR2p and SEC61p
      and accumulation of precursor forms of proteins that have to translocate across
      the ER membrane (KAR2p, alpha factor). Cytosolic proteins (SSA1p and 2p) and
      mitochondrial proteins (CYT c1p and F1 beta p) are not affected. N-terminal
      truncated P-450 proteins remain in the cytoplasm and fail to induce membrane
      proliferation, KAR2p/SEC61p expression, and precursor accumulation. Membrane and
      precursor protein accumulation are typical features of sec mutants. We assume
      that the high amounts of P-450p block one or more factor(s) of the transport
      machinery and thereby cause the observed phenomena.

PMID- 8274498
TI  - Heteroacid phosphatidylcholines with different amounts of unsaturation respond
      differently to cholesterol.
AB  - The effectiveness of cholesterol in removing the gel to liquid crystal phase
      transition of dispersions of pure molecular species of phosphatidylcholines (PC)
      that is detectable by differential scanning calorimetry (DSC) has been explored.
      The effect of cholesterol on 16:0-18:0 PC, 16:0-18:1 PC, 16:0-18:2 PC, 16:0-20:4
      PC and 16:0-22:6 PC has been determined. Cholesterol caused a concentration
      dependent removal of the detectable phase transitions in all cases. It required
      very little cholesterol to remove the phase transition 16:0-18:2 PC (< 17 mol% of
      cholesterol in PC). It required > or = 35 mol% cholesterol to remove delta H for
      16:0-18:0 PC and 16:0-22:6 PC. About 20-25 mol% cholesterol caused disappearance
      of the transitional endotherm of 16:0-18:1 PC and 16:0-20:4 PC. The findings
      indicate that the magnitude of the influence of cholesterol on phospholipid is
      dependent on the degree of unsaturation in the lipid.

PMID- 8274499
TI  - ATP activation of plasma membrane yeast H(+)-ATPase shows complex kinetics
      independently of the degree of purification.
AB  - ATP stimulation of plasma membrane H(+)-ATPase activity from a wild baker's yeast
      (Saccharomyces cerevisiae) was followed under conditions of progressive degrees
      of purification. A particular emphasis was put to cover a wide range of
      concentrations which went from 2 microM up to 3000 microM ATP. The preparations
      used were (i) crude membrane fraction, (ii) untreated plasma membrane fraction
      obtained by differential centrifugation, (iii) residual plasma membrane treated
      with Triton X-100, (iv) enzyme solubilized with either Zwittergent 3-14 alone or
      after Triton X-100 treatment. Under all conditions the fitting of the dose
      response curves required an equation composed by the sum of two Michaelian terms.
      Depending on the treatment, the Km values and Vmax values varied. The fitted
      curves displayed a high affinity-low Vmax (Km values of 7-60 microM and Vmax
      values of 0.03-0.50 mumol P(i)/mg per min) and a low affinity-high Vmax component
      (Km values of 408-1960 microM and Vmax values of 0.26-5.82 mumol P(i)/mg per
      min). The complex ATP activation curve of the yeast plasma membrane H(+)-ATPase
      is in line with similar behavior found for the H(+)-ATPase of higher plants and
      all known animal cation transport ATPases.

PMID- 8274500
TI  - Enhanced permeation and stratum corneum structural alterations in the presence of
      dithiothreitol.
AB  - Stratum corneum protein biochemical and biophysical structural contributions to
      the barrier properties of human epidermis were determined in the presence of the
      reducing agent dithiothreitol (DTT). Mannitol and sucrose permeation through
      human epidermis in the presence of 0 to 50 mM DTT in PBS (pH 7.4) was measured in
      symmetric, side-by-side diffusion cells (32 degrees C). DTT enhancement ratios,
      KP(DTT)/KP(PBS), ranging from 1.6 to 32, were dependent on skin donor and DTT
      concentrations. DTT did not alter stratum corneum uptake of mannitol or sucrose
      nor mannitol solubility in DTT/PBS solutions. Stratum corneum biophysical
      structure was ascertained by FTIR in solvent replacement experiments. DTT-induced
      protein conformational alterations were apparent in the emergence of an Amide I
      band near 1615 cm-1, which is generally associated with beta-sheet-like
      conformers. Therefore, DTT alters stratum corneum biophysical structure through
      interactions with proteins. After exposure of stratum corneum protein sheets to
      DTT/PBS solutions, the free thiol concentration increased from < 1 nmol SH/mg
      protein sheet to approx. 130 nmol/mg. The enhanced permeation which increased
      with increasing concentrations of DTT, was associated with diffusion mechanisms
      involving the cornified cells of the stratum corneum. These results indicate that
      corneocyte protein integrity does contribute to barrier function of the skin and
      influences the transport of polar solutes.

PMID- 8274501
TI  - Ontogeny of Na+/D-glucose cotransport in guinea-pig jejunal vesicles: only one
      system is involved at both 20 degrees C and 35 degrees C.
AB  - The kinetic parameters of Na+/D-glucose cotransport were examined in fetal,
      newborn and adult guinea-pig jejunal brush-border membrane vesicles using a
      displacement curve and non-linear regression procedure. Our data indicated the
      presence of a single system with a Km of 0.34 +/- 0.04 mM at both 20 degrees C
      and 35 degrees C. Vmax was increased by about 4-fold when the kinetic experiments
      were performed at 35 degrees C. Since our results were not in agreement with the
      findings of Brot-Laroche et al. (J. Biol. Chem. (1986) 261, 6168-6176) which
      indicated the existence of a distinct D-glucose transport system in the adult
      guinea-pig jejunum at 35 degrees C, we verified the influence of their
      experimental conditions on initial rate uptake measurements. In the presence of D
      sorbitol instead of D-mannitol in the transport media, 70% inhibition of D
      glucose uptake was observed, an effect which was attributable to contamination of
      sorbitol preparations by D-glucose. After removal of glucose contamination D
      sorbitol did not significantly reduce the initial rate of D-glucose transport.
      These results led us to conclude the existence of a single D-glucose transport
      system in the guinea-pig small intestine and to stress the choice of experimental
      conditions as being crucial for an accurate estimation of kinetic parameters.

PMID- 8274502
TI  - The active metabolite hydroxytamoxifen of the anticancer drug tamoxifen induces
      structural changes in membranes.
AB  - The effects of hydroxytamoxifen (OHTAM) on lipid organization of pure
      phospholipid liposomes, native sarcoplasmic reticulum (SR) membranes and
      liposomes of SR lipids were evaluated by intramolecular excimer formation of 1,3
      di(1-pyrenyl)propane (Py(3)Py) and by fluorescence polarization of 1,6-diphenyl
      1,3,5-hexatriene (DPH) and its derivative 3-[p-(6-phenyl)-1,3,5
      hexatrienyl]phenylpropionic acid (DPH-PA). OHTAM promotes alterations in the
      thermotropic profiles of DMPC, DPPC and DSPC. As detected by Py(3)Py and DPH-PA,
      OHTAM induces an ordering effect in the fluid phase and a fluidizing effect in
      the temperature range of the cooperative phase transition. In the gel phase, no
      significant effects are noticed, except for DSPC bilayers, where Py(3)Py and DPH
      PA detect a disordering effect. In the hydrophobic region of the above membrane
      systems probed by DPH, OHTAM induces only a slight fluidizing effect in the range
      of the phase transition and a small ordering effect in the fluid phase. As
      detected by all probes, the drug broadens the transition profile of DMPC and
      shifts the main transition temperature to lower values. However, these effects,
      and so those observed for the fluid phase, decrease as the fatty acyl chain
      length increases. Moreover, the drug removes the pre-transitions of DPPC and DSPC
      bilayers, as probed by Py(3)Py. In fluid SR native membranes and liposomes of SR
      lipids, OHTAM induces a moderate ordering effect in the outer regions of the
      lipid bilayer, as monitored by Py(3)Py and by DPH-PA, DPH failing to detect any
      apparent effect, as observed for the fluid phase of pure phospholipids.
      Apparently, OHTAM distributes preferentially in the outer region of the lipid
      bilayer, without significant effect in the bulk lipid organization of the bilayer
      interior. The changes of OHTAM in the bilayer dynamic properties and the
      different location across the bilayer thickness relative to its drug promoter
      (Custodio et al. (1993) Biochim. Biophys. Acta 1150, 123-129) may be involved in
      the cytostatic activity of tamoxifen.

PMID- 8274503
TI  - A model of mitochondrial creatine kinase binding to membranes: adsorption
      constants, essential amino acids and the effect of ionic strength.
AB  - The quantitative aspects of mitochondrial creatine kinase (mitCK) binding to
      mitochondrial membranes were investigated. A simple adsorption and binding model
      was used for data fitting, taking into account the influence of protein
      concentration, pH, ionic strength and substrate concentration on the enzyme
      adsorption. An analysis of our own data as well as of the data from the
      literature is consistent with the adsorption site of the octameric mitCK being
      composed of 4 amino acid residues with pK = 8.8 in the free enzyme. The pK value
      changes to 9.8 upon binding of the protein to the membrane. Lysine is suggested
      as the main candidate to form the adsorption site of mitCK. Deprotonated
      octameric mitCK easily dissociated from the membrane (Ka = 0.39 mM at ionic
      strength I = 7.5 mM and 5 degrees C); after protonation its affinity increased
      many times (Kah = 39 nM). Determination of mitCK adsorption capacity by another
      method at pH 7.4, when the enzyme is almost protonated, gave Kah = 15 nM. The
      effect of ionic strength on mitCK adsorption may be described in terms of Debye
      Huckel's theory for activity coefficients assuming the charges of the interacting
      species to be +4 and -4. The dissociation constant for the mitCK-membrane complex
      at pH 7.4 and I = 0 was evaluated by different approaches as approx. 1 nM.
      Extramitochondrial ATP (or ADP) shifted greatly the equilibrium between the
      adsorbed and the free mitCK towards the solubilized state, since in the adsorbed
      protein the external ligands had access to four binding sites and in the free
      protein to eight sites.

PMID- 8274504
TI  - Interactions of liposomes and hydrophobically-modified poly-(N
      isopropylacrylamides): an attempt to model the cytoskeleton.
AB  - The interactions of small unilamellar vesicles (SUV) and water-soluble copolymers
      were studied by fluorescence spectroscopy, differential scanning calorimetry
      (DSC) and quasi-elastic light scattering (QELS). The anchoring onto liposomal
      bilayer membranes of copolymers of N-isopropylacrylamide, N-(2-(1-naphthyl)ethyl)
      N-n-octadecylacrylamide and or N-[4-(1-pyrenyl)butyl]-N-n-octadecylacrylamide
      (0.5 mol% of the octadecylacrylamide comonomer) was monitored by non-radiative
      energy transfer between excited naphthalene and pyrene. The anchoring process
      occurred on zwitterionic lecithin liposomes and on negatively charged
      phosphatidic acid liposomes, whether the bilayer was in the crystalline or the
      liquid-crystalline phase. Insertion of the copolymer octadecyl groups within
      crystalline bilayers was attributed to the presence of packing defects. Aqueous
      solutions of poly-(N-isopropylacrylamide) and of its hydrophobically-modified
      copolymers exhibit a lower critical solution temperature (LCST). The coil to
      globule collapse of the polymer chains which is known to occur as the aqueous
      solution is heated through the LCST, also took place when the copolymers were
      anchored onto vesicular bilayers. The copolymers remained anchored during this
      collapse and the liposomes were not destroyed. The process was thermo-reversible.
      Detailed aspects of the reversibility of the phenomenon depended on the relative
      values of the phase transition temperatures of the liposomes and of the polymer
      LCST.

PMID- 8274505
TI  - An Escherichia coli gene showing a potential ancestral relationship to the genes
      for the mitochondrial import site proteins ISP42 and MOM38.
AB  - An ORF (OrfT) of 1911 base pairs, upstream of the hip operon in Escherichia coli
      at map position 33.82 has been identified. The protein encoded by this sequence
      is predicted to have a molecular mass of 68,249 Da and the carboxyterminal 276
      residues shows 26.8% and 25.4% identity with the import site proteins ISP42 and
      MOM38 from the mitochondrial outer membrane of Saccharomyces cerevisiae and
      Neurospora crassa, respectively. These mitochondrial membrane proteins have been
      shown to be essential components of the protein translocation apparatus in yeast.
      These similarities raise the possibility that OrfT might represent the bacterial
      gene from which these eukaryotic genes evolved.

PMID- 8274506
TI  - [Modeling the phytochrome structure].
AB  - Secondary structures of phytochromes from five plant species have been calculated
      by the method based on the theory of short- and long-range interactions in
      proteins. It has been shown that the predicted content of the elements of
      secondary structure in different phytochrome molecules varies at standard
      conditions for alpha-helix (33-38%), beta-sheet (15-23%), beta-turn (14-16%), and
      random coil (24-33%). A model for the fragment of the oat phytochrome consisting
      of amino-acid residues from 205 to 350 has been proposed.

PMID- 8274507
TI  - [Dual-impact mechanism of photosensitized cell damage].
AB  - Dose dependencies of the rate of hematoporphyrin sensitized photolysis of
      erythrocytes and leucocytes have been investigated. It has been shown that power
      index of dose dependency for erythrocytes equal 2, while for leucocytes it lies
      between 1 and 2, suggesting heterogeneity of total leucocyte fraction in
      photosensitivity.

PMID- 8274508
TI  - [Membrane control of the photodeblocking reaction of cytochrome oxidase in the
      mitochondrial electron transport chain].
AB  - Hyperosmotic shrinkage and hypoosmotic swelling of the internal mitochondrial
      membrane decrease considerably the efficiency of the reaction of the cyanide
      photodissociation from the cytochrome oxidase. The osmotic effect increases after
      the reduction of the membrane potential by a protonophore uncoupler. This
      suggests that the local photochemical reaction is subject to membrane control.

PMID- 8274509
TI  - [Use of kinetics of Fe+2-induced chemiluminescence in a tris-buffer liposome
      suspension for studying the antioxidant activity of blood plasma].
AB  - In order to evaluate antioxidant activity (AOA) of different preparations in
      respect to Fe(2+)-induced lipid peroxidation (LPO) chemiluminescence (CL)
      kinetics in tris-buffer liposome suspension was proposed. For studying AOA stages
      of fast flash, latent period and slow flash related to LPO reaction development
      were used. The measurement of CL kinetic parameters along with malondialdehyde
      accumulation makes it possible to determine also the mechanism of antioxidant
      effect on the preparations under consideration. The mechanism of AOA of the blood
      plasma is mainly due to transferrin, ceruloplasmin and HCO3- interaction with
      Fe2+ leading to abstraction of some part of ferrous ions participated in LPO
      reactions. In the case of albumin the change of CL kinetic parameters was
      proposed to be conditioned by the competition with ferrous ions for binding sites
      on liposomes. The effect of a-tocopherol at physiological concentrations compared
      with other blood plasma components in this system was negligibly small.

PMID- 8274511
TI  - [Membrane potentials and adaptive abilities of lymphocytes and erythrocytes in
      various states of mammalian activities].
AB  - The hypothesis about system of bioelectrical regulation of life activities by
      single parameter was proposed at the beginning of our century. To check this
      hypothesis at cellular level the simultaneous research of average values of
      membrane potential (MP) and regulatory capacities of erythrocytes and lymphocytes
      of mice at two different levels of life activities of organisms (mice without
      diseases and mice, in organisms of which inflammatory process develops) was
      carried out. It was shown, that average values of MP of these cells, as far as
      their regulatory capacities under hypotonic conditions, were different at the
      different levels of life activities of mice, but were similar for erythrocytes
      and lymphocytes at each tested level. The identical behaviours of the cells of
      two populations in spite of functions they fulfil in organism convince, that the
      hypothesis about system of bioelectrical regulation of life activities by single
      parameter (i.e. MP) may be true.

PMID- 8274510
TI  - [Photobiological processes in biomembranes under the effect of ultraviolet
      radiation on animal cells, tissues, and organs].
AB  - The current knowledge about the mechanisms of the lipid photoperoxidation (LPPO)
      and the role of the process in the effects of the UV-irradiation of cells and
      tissues is reviewed. The LPPO in biomembranes occurs as a result of the lipid
      hydroperoxide phototransformation to free radicals and the antioxidant
      photolysis. The LPPO significantly depends on the structural state of
      biomembranes. The UV-radiation stimulates the two types of dark lipid
      peroxidation (LPO): the free radical non-enzymatic peroxidation, and the
      cyclooxygenase peroxidation. The UV-radiation produces increase of the membrane
      ion permeability, decrease (or enhancement) of the aggregatory interaction of
      cells, and changes of the membrane enzymatic activity. The LPPO and the dark non
      enzymatic LPO play an important role in the changes of the membrane functions
      under the UV-irradiation. The dark non-enzymatic LPO is important for the
      development of UV erythema. The cyclooxygenase LPO may be responsible for the
      curative properties of the UV-irradiated blood.

PMID- 8274512
TI  - Synthesis and characterization of a penicillin-poly(L-lysine) which recognizes
      human IgE anti-penicillin antibodies.
AB  - Conjugates of poly(L-lysine) containing a penicillin or a penicilloyl residue
      were prepared and characterized by 1H NMR and by size-exclusion HPLC. These
      conjugates and conjugates with human serum albumin were used in
      radioallergosorbent tests (RAST) for the determination of allergy toward
      penicillins.

PMID- 8274513
TI  - Protected thiol-polyethylene glycol: a new activated polymer for reversible
      protein modification.
AB  - Monomethoxypolyethylene glycol (mPEG) of average molecular weight 5000 was
      transformed in a series of synthetic steps to a new activated form of PEG, a
      stable thiol-protected intermediary, for reaction with cysteine residues in
      proteins under mild conditions to produce PEG--protein conjugates as possible
      candidates for therapeutics. The modified protein has PEG polymer molecules
      attached to the backbone by the newly formed disulfide bonds, which are readily
      cleaved to regenerate the native protein under mild reducing conditions. The
      model protein papain, which has seven cysteine residues including a lone cysteine
      in its active site, was modified through the free available thiol. The resulting
      PEG--papain was characterized by matrix-assisted laser desorption mass
      spectrometry, SDS-PAGE, and high performance gel filtration chromatography. The
      major modified PEG--papain variant was demonstrated to be 5000 Da larger than the
      unreacted papain.

PMID- 8274514
TI  - Oligonucleotide derivatives bearing reactive and stabilizing groups attached to
      C5 of deoxyuridine.
AB  - Oligonucleotides bearing an aliphatic amino group at the C5-position of
      deoxyuridine (ULNH2TCCCA, TULNH2CCCA, ULNH2CCACTT, where L = -CH2-, -CH2OCH2CH2-
      or -CH2NHCOCH2CH2-) have been synthesized. The photoactive (p
      azidotetrafluorobenzamido, 2-nitro-5-azidobenzamido, or p-azidobenzamido),
      alkylating [4-[N-(2-chloroethyl)-N-methylamino]benzyl], or intercalating [N-(2
      hydroxyethyl)phenazinium] groups were attached to the amino linker of
      oligonucleotides. The Tm values were determined for the duplexes formed by the
      above oligonucleotide derivatives. The alkylating group does not change the
      melting temperature of the corresponding duplex. The duplex stability is
      increased a little in the case of photoactive groups. The influence of the
      phenazinium residue on the duplex stability strongly depends on its location in
      the oligonucleotide. The spacer length between the C5 atom of deoxyuridine and
      the photoactive or phenazinium group was shown to influence the complementary
      duplex stability.

PMID- 8274515
TI  - Synthesis, characterization, and in vitro evaluation of nitroimidazole--BATO
      complexes: new technetium compounds designed for imaging hypoxic tissue.
AB  - Several technetium-99 BATO (boronic acid adduct of technetium dioximes) complexes
      TcX(dioxime)3BR (X = Cl) that contain a boron cap R which bears a 2- or 4
      nitroimidazole moiety have been prepared from either TcCl(dioxime)3 or from
      Tc(dioxime)3(mu-OH)SnCl3 [dioxime = dimethyl glyoxime (DMG) or cyclohexanedione
      dioxime (CDO)]. Two hydroxy analogs (X = OH) were isolated by treatment of the
      corresponding chloro complexes with aqueous NaOH. The complexes have been
      characterized by elemental analysis, mass spectrometry, NMR, UV/vis spectroscopy,
      and high-performance liquid chromatography. These complexes have the potential
      for selective retention in hypoxic tissue, by a mechanism believed to be the
      result of nitro reduction. The electrochemistry and enzymatic reduction of these
      complexes was studied to assess the potential for reduction in vivo. The
      nitroreductase enzyme xanthine oxidase was shown to reduce the nitroimidazole
      group on the complexes 99TcOH(DMG)3BBNO2 and 99TcOH(DMG)3BprenNO2 under anaerobic
      conditions in the presence of hypoxanthine. However, the results indicated that
      the rate of reduction might be slow in vivo, limiting the suitability of these
      compounds for imaging of regions of hypoxia.

PMID- 8274516
TI  - Antitumor activities of a cephalosporin prodrug in combination with monoclonal
      antibody-beta-lactamase conjugates.
AB  - 7-(Phenylacetamido)cephalosporin mustard (CM) and 7-(4
      carboxybutanamido)cephalosporin mustard (CCM) were developed as anticancer
      prodrugs that could be activated site selectively by monoclonal antibody-beta
      lactamase conjugates targeted to antigens present on tumor cell surfaces. Both CM
      and CCM were hydrolyzed by purified beta-lactamases from Escherichia coli (EC
      beta L), Bacillus cereus (BC beta L), and Enterobacter cloacae (ECl beta L). This
      resulted in the release of phenylenediamine mustard (PDM), a potent cytotoxic
      drug. The Km and kcat values of the reactions were determined, and it was found
      that ECl beta L effected the hydrolysis of CM and CCM more rapidly than the other
      enzymes. Conjugates of ECl beta L were prepared by reacting maleimide-substituted
      F(ab')2 fragments of the monoclonal antibodies L6 and P1.17 to ECl beta L that
      had been modified with sulfhydryl groups. In vitro experiments indicated that CCM
      (IC50 = 25-45 microM) was less toxic than PDM (IC50 = 1.5 microM) to H2981 lung
      adenocarcinoma cells (L6 antigen positive, P1.17 antigen negative) and that
      immunologically specific prodrug activation took place when the cells were
      treated with L6-ECl beta L. In vivo experiments in nude mice demonstrated that
      CCM was less toxic than CM, and that both prodrugs were much less toxic than PDM.
      Neither CCM nor PDM exerted antitumor activity on subcutaneous H2981 tumors in
      vivo. However, a significant antitumor effect was obtained in mice that received
      L6-ECl beta L 96 h prior to the administration of CCM. The effect was
      immunologically specific (P < 0.05), since a smaller degree of antitumor activity
      was obtained in mice that received the nonbinding control conjugate P1.17-ECl
      beta L prior to CCM.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274517
TI  - Temperature-responsive bioconjugates. 2. Molecular design for temperature
      modulated bioseparations.
AB  - We have synthesized carboxyl semitelechelic oligo(N-isopropylacrylamide) (OIPAAm)
      using radical telomerization with 3-mercaptopropionic acid. This telomerization
      is also effective for the synthesis of carboxyl semitelechelic co-oligomers of
      IPAAm with butyl methacrylate (BMA) as hydrophobic or N,N-dimethylacrylamide
      (DMAAm) as hydrophilic comonomers. All co-oligomers are highly water-soluble at
      lower temperatures and exhibit phase separation with increasing temperature. Pure
      OIPAAm exhibits a lower critical solution temperature (LCST) at 32 degrees C, and
      the LCST for co-oligomers can be controlled to increase over 32 degrees C with
      increasing DMAAm composition and to decrease below 32 degrees C with increasing
      BMA composition. OIPAAm was grafted to bovine serum albumin (BSA) and bovine
      plasma fibrinogen (BPF) by activated ester-amine coupling. These OIPAAm
      biomolecule conjugates maintain their temperature responses, are soluble in cold
      water, and precipitate over a range of temperatures related to oligomer content.
      Conjugates could be selectively precipitated and independently separated from
      conjugate solution mixtures with increasing temperature. In this case, the number
      of OIPAAm molecules attached to a conjugate affects the aggregate sizes of
      precipitated conjugates in mixtures. Both conjugate mixture ratios and solution
      concentrations influence the contamination of oligo(IPAAm-co-DMAAm)-BSA
      conjugates in precipitated oligo(IPAAm-co-BMA)-BPF conjugates. Furthermore,
      precipitated conjugates separated using centrifugation and filtration redissolve
      in water and maintain their biofunctionality, indicating the potential of
      strategy in reversible bioreactors and protein separations.

PMID- 8274518
TI  - Antibody-magnetite nanoparticles: in vitro characterization of a potential tumor
      specific contrast agent for magnetic resonance imaging.
AB  - Target-specific superparamagnetic contrast agents may allow the localization of
      specific tissues such as tumors by magnetic resonance imaging (MRI). In this
      report the preparation and in vitro characterization of tumor-specific
      superparamagnetic particles (SMP) are described. Particles of uniform size (9.6
      +/- 0.8 nm) were prepared from an alkaline solution of ferric and ferrous ions
      and isolated by differential centrifugation. The resulting nanoparticle
      suspension is stabilized in buffer using a polypeptide coat to which a monoclonal
      antibody, specific to carcinoembryonic antigen (CEA), was covalently attached at
      the hinge region. The resulting anti-CEA SMP have a hydrodynamic radius of less
      than 50 nm, and specifically bind to CEA in vitro. The visualization of epitopes,
      present on a cell surface in very low density as expected for tumor antigens or
      receptors, may be achieved due to the high R2 relaxivity of 300 L mmol-1s-1 of
      the contrast agent described here. Furthermore, the polypeptide coat chosen
      provides an ideal platform for the attachment of biological modifiers needed for
      the reduction of the antigenicity and blood clearance rate of anti-CEA SMP.

PMID- 8274519
TI  - Application of monoclonal antibodies against cytosine deaminase for the in vivo
      clearance of a cytosine deaminase immunoconjugate.
AB  - The selective delivery of anticancer drugs to tumors vs normal tissue using
      targeted antibody-enzyme conjugates for prodrug activation is limited by the
      amount of drug generated by blood-borne enzyme. Clearance of non-tumor-associated
      conjugate would increase the tumor/blood conjugate ratio, and enable larger
      amounts of prodrugs to be administered. A method for clearing the monoclonal
      antibody (mAb) conjugate L6-cytosine deaminase (L6-CD) was established by using
      an antibody raised against CD. The mAb 102-26 was obtained by immunizing BALB/C
      mice with CD conjugated to keyhole limpet hemocyanin. 102-26 was able to
      precipitate purified CD from solution as assessed by radioimmune precipitation
      and recognized CD in Western blot analyses. Similar studies were used to
      establish that 102-26 also recognized CD when conjugated to the L6 and 1F5 mAbs.
      Selective removal of L6-CD from the circulation of nude mice bearing H2981 human
      lung adenocarcinoma (L6-antigen positive) was achieved by injecting 102-26 24 h
      after L6-CD administration. High T/B ratios were obtained by clearance of a L6-CD
      (38:1 compared to 1.3:1 without clearance).

PMID- 8274520
TI  - Trypsin modification by vinyl polymers with variable solubilities in response to
      external signals.
AB  - Trypsin was modified with various vinyl polymers by the graft polymerization of
      vinyl monomers using a trypsin derivative containing aliphatic azo groups as the
      initiator. The graft polymers were chosen to be sensitive to external signals,
      e.g., a redox-sensitive poly[3-carbamoyl-1-(p-vinylbenzyl)pyridinium chloride]
      and a pH-sensitive poly(methacrylic acid-co-methyl methacrylate). The trypsin
      modified with the redox-sensitive polymer became insoluble in water in the
      presence of Na2S2O4, and redissolved when H2O2 was added. However, the enzymatic
      activity of the homogeneous solution was not proportional to the concentration of
      the modified trypsin remaining in the solution. The trypsin modified with the pH
      sensitive polymer was insoluble and soluble in acidic and neutral solutions,
      respectively. The enzymatic activity of the homogeneous solution changed
      reversibly with pH in proportion to the concentration of the modified trypsin
      remaining in the solution.

PMID- 8274521
TI  - Bisulfite ion-catalyzed transamination of cytosine residues with alpha, omega
      alkanediamines: the effect of chain length on the reaction kinetics.
AB  - Pseudo-first-order rate constants for the bisulfite ion-catalyzed transamination
      of cytidine with 1,2-ethanediamine, 1,3-propanediamine, 1,4-butanediamine, and
      1,6-hexanediamine have been determined. Hydrolytic deamination has been shown to
      compete with transamination under acidic conditions, but is of minor importance
      at pH > 5.3 when the total concentration of diamine is greater than 0.2 mol dm-3.
      The dependence of the transamination rate on pH and the concentration of diamine
      and bisulfite ion indicates that the major reaction involves nucleophilic attack
      of the diamine monocation on the N3 protonated bisulfite adduct of cytidine. The
      effect of the chain length of the diamine on the rate of transamination is
      discussed, and the results are compared with those obtained by reacting single
      stranded DNA with the same diamines and labeling the transaminated product with a
      europium chelate.

PMID- 8274522
TI  - Preparation of hybrid "DNA cleaver-oligonucleotide" molecules based on a
      metallotris(methylpyridiniumyl)porphyrin motif.
AB  - Methods are reported for conjugating a cationic tris(methylpyridiniumyl)porphyrin
      manganese(III) complex to oligonucleotides. The DNA cleaver motif used in the
      present work is related to Mn-TMPyP, a highly efficient artificial endonuclease
      able to hydroxylate C-H bonds of DNA sugars at nanomolar concentrations. A
      general coupling method has been developed by using porphyrin precursors having a
      linker attached at the para position of the meso phenyl group of the macrocycle
      and terminating with an activated ester of 1-hydroxybenzotriazole. Coupling
      reactions were monitored by HPLC. Purification of metalloporphyrin
      oligonucleotide conjugates was performed by HPLC and desalting on Bio-Gel P-2.
      The purity of conjugates was always above 95%.

PMID- 8274523
TI  - Polyamidoamine cascade polymers mediate efficient transfection of cells in
      culture.
AB  - Cascade polymers also known as Starburst dendrimers are spheroidal polycations
      that can be synthesized with a well-defined diameter and a precise number of
      terminal amines per dendrimer. We show, using luciferase and beta-galactosidase
      containing plasmids, that dendrimers mediate high efficiency transfection of a
      variety of suspension and adherent cultured mammalian cells. Dendrimer-mediated
      transfection is a function both of the dendrimer/DNA ratio and the diameter of
      the dendrimer. Maximal transfection of luciferase are obtained using a diameter
      of 68 A and a dendrimer to DNA charge ratio of 6/1 (terminal amine to phosphate).
      Expression is unaffected by lysomotrophic agents such as chloroquine and only
      modestly affected (2-fold decrease) by the presence of 10% serum in the medium.
      Cell viability, as assessed by dye reduction assays, decreases by only 30% at 150
      micrograms dendrimer/mL in the absence of DNA and about 75% in the presence of
      DNA. Under similar conditions polylysine causes a complete loss of viability.
      Gene expression decreased by 3 orders of magnitude when the charge ratio is
      reduced to 1:1. When GALA, a water soluble, membrane-destabilizing peptide, is
      covalently attached to the dendrimer via a disulfide linkage, transfection
      efficiency of the 1:1 complex is increased by 2-3 orders of magnitude. The high
      transfection efficiency of the dendrimers may not only be due to their diameter
      and shape but may also be caused by the pKa's (3.9 and 6.9) of the amines in the
      polymer. The low pKa's permit the dendrimer to buffer the pH change in the
      endosomal compartment. The characteristics of precise control of structure,
      favorable pKa's, and low toxicity make the dendrimers suitable for gene-transfer
      vehicles.

PMID- 8274524
TI  - End attachment of phenol-oligonucleotide conjugates to diazotized cellulose.
AB  - The synthesis of a novel phosphoramidite reagent with a hexanediol backbone is
      described. This reagent has been used to incorporate a phenol moiety on an
      oligonucleotide (ODN) directly in the course of its automated synthesis. Multiple
      phenol attachments can be achieved by repetitive coupling cycles. A simple and
      rapid immobilization method is described where phenol-modified ODNs are
      covalently attached to diazotized cellulose. The binding capacity of the membrane
      can be modulated, depending on the ODN concentration used, to ca. 180 pmol/cm2.
      There is at least 80% end attachment of the ODN through the phenol group. In
      addition, the phenol residue can be used as a carrier for the radiolabeling with
      125I. The non-nucleosidic hexanediol derivative incorporated at the 5'-end of the
      ODN is recognized as a substrate by the T4 polynucleotide kinase and the terminal
      hydroxyl group is successfully phosphorylated allowing its 32P labeling.

PMID- 8274525
TI  - Automated synthesis of oligodeoxyribonucleoside methylphosphonates having [N-(3
      aminoprop-1-yl)-N-(2-hydroxyethyl)-2-aminoethyl] phosphate or methylphosphonic
      acid at the 3' end using a modified controlled pore glass support.
AB  - To provide a solid support for automated synthesis of 3'-(aminoalkyl)-modified
      oligonucleoside methylphosphonates, controlled pore glass beads were
      functionalized with a protected N-(3-aminoprop-1-yl)-N-(2-hydroxyethyl)-2
      aminoethyl ester of succinic acid. This "Aha-CPG" was used for automated
      synthesis of oligo-2'-deoxyribonucleoside methylphosphonates having either of two
      distinct 3' terminal modifications. If the first coupling to the beads was of a
      base-protected 5'-(dimethoxytrityl)-2'-deoxyribonucleoside 3'-(beta-cyanoethyl
      N,N-diisopropylphosphoramidite) synthon, then, upon completion of
      methylphosphonate oligomer synthesis and deprotection, the 3'-[N-(3-aminoprop-1
      yl)-N-(2-hydroxyethyl)-2-aminoethyl] phosphate] derivative of an oligonucleoside
      methylphosphonate was produced and was shown to be a stable structure which
      affords a primary alkylamine group suitable as a site for further conjugations.
      If the first coupling was of a 5'-(dimethoxytrityl)-2'-deoxyribonucleoside 3'
      (N,N-diisopropylmethylphosphonamidite) synthon, the initial product of synthesis
      and deprotection underwent a spontaneous, regiospecific ester cleavage in aqueous
      solution to produce an oligonucleoside methylphosphonate 3'-(methylphosphonate).
      An application of the Aha-CPG to the synthesis of rhodamine-conjugated
      oligonucleoside methylphosphonates is described in a companion paper [Thaden, J.
      and Miller, P. S. (1993) Bioconjugate Chem., preceding paper in this issue].

PMID- 8274526
TI  - Synthesis of 3-(triethylstannyl)propanoic acid: an organotin mass label for DNA.
AB  - The synthesis of 3-(triethylstannyl)propanoic acid (TESPA), an organometallic
      reporter group that enables the mass labeling of oligonucleotides with stable
      isotopes of tin, is described. Synthesized from commercially available
      isotopically-enriched SnO2 in a five step process, the NHS ester of TESPA is
      produced with an overall yield of 40%. This simplification of the standard
      synthetic scheme, with two less synthetic steps and a coincident 60% yield
      increase, is accomplished through the use of the reagent N-(acryloxy)succinimide
      and the free radical initiator AMPN. The conditions for the attachment of the
      reporter group to priming oligonucleotides and the subsequent HPLC isolation of
      the labeled primers are also detailed.

PMID- 8274527
TI  - A mechanism for valine-resistant growth of Escherichia coli K-12 supported by the
      valine-sensitive acetohydroxy acid synthase IV activity from ilvJ662.
AB  - Acetohydroxy acid synthase (EC 4.1.3.18; AHAS) isozymes I and III are expressed
      in Escherichia coli strain K-12 and, when inhibited by L-valine, cannot support
      cell growth. AHAS IV, expressed from mutation at ilvJ662, exhibits valine
      sensitivity similar to that of AHAS III, yet AHAS IV does support cell growth in
      valine minimal medium. Rate equations were derived for AHAS III and AHAS IV
      reaction in crude extracts and for partially purified AHAS IV. Values of kinetic
      constants in these equations were determined in order to model a probable
      reaction mechanism. Computer modeling of initial velocity reactions at
      physiological substrate concentrations simulated consequences of valine
      inhibition and revealed that AHAS IV synthesized AHB at a maximal rate over four
      times faster than AHAS III under these conditions. The simulations predicted that
      cells depending upon AHAS III for growth in valine minimal medium would
      accumulate higher levels of 2-ketobutyrate than cells using AHAS IV. Experiments
      on growth inhibition by valine revealed more than a five-fold difference in 2
      ketobutyrate accumulation, thus confirming these predictions. These data support
      the hypothesis that valine inhibition of growth is a consequence of 2
      ketobutyrate accumulation to toxic levels. We propose that the valine-inhibited
      AHAS IV activity prevents growth inhibition by keeping 2-ketobutyrate
      accumulation to a lower level than resulting from AHAS III activity.

PMID- 8274528
TI  - Iron: metabolism, toxicity and therapy.
AB  - This paper is an overview on iron metabolism, iron toxicity and therapeutics
      against this toxicity. The attention has been focused on: i) the solubilization
      of iron by living organisms; ii) the iron metabolism in human; iii) the toxicity
      of iron (Fe-catalyzed reduction of oxygen, Fenton reaction, decomposition of
      lipid peroxides); iv) the natural protective mechanisms; v) the relations between
      iron, free radicals and human diseases; and vi) the iron overload and its
      treatment.

PMID- 8274529
TI  - Expression of the recA gene in recombination-deficient (rec-) strains of
      Escherichia coli.
AB  - Basal and induced levels of recA expression in wild-type and isogenic derivatives
      of Escherichia coli carrying various rec mutations were measured using a low-copy
      number recApo-lacZ fusion, pKLC3.2. Basal recA expression in wild-type and
      isogenic derivatives containing single rec- mutations, as well as in the
      recBCsbcA strain and isogenic recA, recF and recJ derivatives, ranged from 1000
      to 3900 units. In the recBCsbcBC strain and isogenic recL and recN derivatives
      basal recA expressions were 3- to 5-fold higher than that of wild-type cells and
      were inducible by mitomycin C. Except for the recA and lexA3(lnd-) mutants, recA
      expression was induced by mitomycin C in wild-type cells and its isogenic recB,
      recD, recF, recG, recJ, recL, recN, recO and ruv derivatives. RecF was required
      for induction of recA expression by mitomycin C, but not by naladixic acid in the
      recBCsbcA and recBCsbcBC genetic backgrounds. In wild-type cells, induction of
      recA expression by naladixic acid required the recBC, but not the recD function
      of the RecBCD enzyme. This requirement is suppressed by either an additional sbcA
      or sbcC mutation, but not by an sbcB mutation.

PMID- 8274530
TI  - The complete nucleotide sequence of chicken ribosomal protein L7a gene and the
      multiple factor binding sites in its 5'-flanking region.
AB  - The nucleotide sequence of the gene encoding chicken ribosomal protein L7a was
      determined. The gene contains eight exons and seven introns, which spread over
      3613 nucleotides. The transcription initiation sites were located on four
      consecutive nucleotides GCCC, which are at the 5' terminus of a short
      polypyrimidine tract of eight base-pairs flanked by G + C-rich regions. Neither a
      canonical TATA nor a CAAT box was found in the 5'-flanking region. Instead, a
      short A + T-rich stretch was found at the position where the TATA box is expected
      to be. There is an intensive nuclear protein binding motif repeated four times in
      the region -134 to -50. This motif is common to many ribosomal protein genes and
      may play an important role in the control of ribosomal protein gene expression.

PMID- 8274531
TI  - Pyruvate kinase from Lactobacillus bulgaricus: possible regulation by competition
      between strong and weak effectors.
AB  - The pyruvate kinase from Lactobacillus bulgaricus has been purified to
      homogeneity. The native enzyme is composed of four probably identical subunits of
      relative molecular mass M(r) 72,000 +/- 4,000. The unique N-terminal amino acid
      sequence is homologous to those of other pyruvate kinases, especially of type I
      and II enzymes from Escherichia coli. The saturation of the pyruvate kinase from
      Lactobacillus bulgaricus is hyperbolic for ADP and cooperative for the other
      substrate phospho-enol-pyruvate. The enzyme is strongly activated by glucose-6
      phosphate, ribose-5-phosphate, and fructose-6-phosphate, which increase the
      affinity for phospho-enol-pyruvate. These activators seem to stabilize the same
      state of the enzyme, since their maximum activations are not additive, but their
      partial activations can be cumulated. Pyruvate kinase is also weakly activated by
      AMP and inhibited by fructose-1,6-bisphosphate. However, both AMP and fructose
      1,6-bisphosphate act as strong inhibitors in the presence of a strong activator,
      because these weak effectors suppress the activation by glucose-6-phosphate,
      ribose-5-phosphate, or fructose-6-phosphate. This mutual exclusion of strong and
      weak effectors, which appears as an original regulatory mechanism, could reflect
      either the binding of different effectors to different interacting sites or their
      competition for a unique polyvalent regulatory site in the pyruvate kinase from
      Lactobacillus bulgaricus.

PMID- 8274532
TI  - Purification and properties of bovine thioredoxin system.
AB  - Using a variety of chromatographic techniques, a crude extract from bovine liver
      was fractionated to obtain pure preparations of thioredoxin reductase,
      thioredoxin, glutaredoxin and glutathione reductase with good yields. The
      turbidimetric assay of thioredoxin with insulin as the disulfide substrate was
      optimized; by incorporation of the lag time (tau) into the calculations,
      linearity was maintained for a wider range of thioredoxin concentrations, and a
      distinction could be made between reduced and non-reduced forms. Subunit
      composition and molecular mass, absorption spectrum and kinetic parameters of
      thioredoxin reductase were similar to those of other mammalian thioredoxin
      reductases. By chromatofocusing, two peaks of activity were detected at pH 5.5
      and 5.8. Structural changes undergone by the thioredoxin molecule upon oxido
      reduction were detected by isoelectric focusing, with a shift of 0.1 pH unit of
      its pI, and by analytical anion exchange chromatography, with a conspicuous shift
      of its retention time. These two methods also revealed the presence of a form of
      thioredoxin not undergoing the above mentioned redox-mediated structural shifts
      that accounted for > 75% of the total activity.

PMID- 8274533
TI  - Evidence for up-regulated low density lipoprotein receptor in human lung
      adenocarcinoma cell line A549.
AB  - Human lung adenocarcinoma cell line A549 was studied with respect to the
      metabolism of human low density lipoprotein (LDL) and 3-hydroxy-3-methyl-glutaryl
      coenzyme A reductase (HMGR) activity. After incubation in medium containing
      lipoprotein-deficient serum (LPDS) for 24 h, the A549 cell line expresses a
      single class of high affinity LDL binding sites (KD at 37 degrees C of 15.1 +/-
      0.7 nM and capacity of 118 +/- 2.8 ng/mg cell protein) and an HMGR activity of
      111.4 +/- 7 pmol/min/mg cell protein. After binding, the LDLs were internalized
      and degraded by a common saturable process. The HMGR activity was higher in A549
      cells than in fibroblasts but LDL affinity and binding capacity were similar in
      both cell types. However, in the presence of lipoproteins, A549 cells showed a
      two-fold higher binding capacity than fibroblasts. When the cells were deprived
      of cholesterol, the amount of LDLR sites increased but the extent of stimulation
      was lower in A549 than in fibroblast cells (2.5-fold versus six-fold
      respectively). This increase was accompanied by a similar increase in the
      specific LDLR mRNA cellular levels (two-fold versus six-fold respectively). When
      cells were deprived of exogenous and endogenous cholesterol (biosynthesis blocked
      by compactin), the binding capacity and the LDLR mRNA levels were yet again
      increased in A549 cells but not in fibroblasts. Taken together these results
      suggest that the level of expression of the LDLR is up-regulated in A549 cells
      compared to fibroblasts.

PMID- 8274534
TI  - Individual levels of activity of O6-alkylguanine-DNA alkyltransferase in monkey
      gastric mucosa during chronic exposure to a gastrocarcinogen N-ethyl-N'-nitro-N
      nitrosoguanidine.
AB  - The activity of a DNA repair enzyme, O6-alkylguanine-DNA alkyltransferase (AGT),
      was studied in gastric mucosa of 15 Macaca fascicularis monkeys before and during
      chronic oral exposure to the ethylating carcinogen N-ethyl-N'-nitro-N
      nitrosoguanidine (ENNG) in order to investigate possible causes of inter
      individual differences in susceptibility to its gastrocarcinogenic effect. A wide
      range of AGT activity (307-1903 fmol/mg protein, mean 695) was found before
      treatment and it decreased during the first year of exposure (means 627, 479 and
      452 fmol/mg protein respectively at 6, 12 and 18 months after the beginning of
      the experiment). The carcinogenesis study is under way and to date four monkeys
      with low initial AGT level in gastric mucosa died of gastric cancer. The
      relevance of AGT level measurement for prediction of individual susceptibility to
      ENNG is discussed.

PMID- 8274535
TI  - Influence of glucose on the deoxyglucose metabolism in S cerevisiae: detection
      and identification of deoxyglucose and trehalose derivatives by 1H- and 13C-NMR
      spectroscopy.
AB  - The metabolism of 2-deoxy-D-glucose (DG) in glucose grown repressed Saccharomyces
      cerevisiae cells was studied in the absence and presence of glucose (Glc) at 30
      degrees C in a standard pyrophosphate medium containing 4.5 x 10(7) cells/ml. 1H-
      and 13C-NMR spectroscopy were successfully used to distinguish and identify
      several derivatives of DG and trehalose. Using [1-13C]DG, alpha- and beta-DG,
      alpha- and beta-DG6P, dideoxy-trehalose (DG-DG) and deoxy-trehalose (DG-Glc) can
      be simultaneously observed in the intracellular medium. The [DG6P]/[DG] ratio is
      about 5-6. The results seem to indicate the existence of an equilibrium between
      DG and DG6P, which limits the production of DG6P in cells. Glucose was found to
      exert a great influence on the metabolism of DG. It favours the formation of DG
      DG and DG-Glc.

PMID- 8274537
TI  - Frequency and burst duration in oscillating neurons and two-cell networks.
AB  - We study the relationship of injected current to oscillator period in single
      neurons and two-cell model networks formed by reciprocal inhibitory synapses.
      Using a Morris-Lecar-like model, we identify two qualitative types of oscillatory
      behavior for single model neurons. The "classical" oscillator behavior is defined
      as type A. Here the burst duration is relatively constant and the frequency
      increases with depolarization. For oscillator type B, the frequency first
      increases and then decreases when depolarized, due to the variable burst
      duration. Our simulations show that relatively modest changes in the maximal
      inward and outward conductances can move the oscillator from one type to another.
      Cultured stomatogastric ganglion neurons exhibit both A and B type behaviors and
      can switch between the two types with pharmacological manipulation. Our
      simulations indicate that the stability of a two-cell network with injected
      current can be extended with inhibitory coupling. In addition, two-cell networks
      formed from type A or type B oscillators behave differently from each other at
      lower synaptic strengths.

PMID- 8274536
TI  - Virtual trajectory and stiffness ellipse during multijoint arm movement predicted
      by neural inverse models.
AB  - We predict the virtual trajectories and stiffness ellipses during multijoint arm
      movements by computer simulations. A two-link manipulator with four single-joint
      muscles and two double-joint muscles is used as a model of the human arm.
      Physical parameters of the model are derived from several experimental data.
      Among them, special emphasis is put on low values of the dynamic hand stiffness
      recently measured during single-joint and multijoint movements. The feedback
      error-learning scheme to acquire the inverse dynamics model and the inverse
      statics model is utilized for this prediction. The virtual trajectories are much
      more complex than the actual trajectories. This indicates that planning the
      virtual trajectory is as difficult as solving the inverse dynamics problem for
      medium and fast movements, and simply falsifies the advocated computational
      advantage of the virtual trajectory control hypothesis. Thus, we conclude that
      learning inverse models is essential even in the virtual trajectory control
      framework. Finally, we propose a new computational model to learn the complicated
      shape of the virtual trajectories by integrating the virtual trajectory control
      and the feedback-error-learning scheme.

PMID- 8274538
TI  - Transient analysis of vestibular nystagmus.
AB  - The significance of a nystagmus-dependent, transient component in the overall
      slow-phase response of the vestibulo-ocular reflex (VOR) is brought into focus.
      First, a simulated example is presented that shows how this transient component
      can bias current algorithms for the estimation of VOR parameters. Second, new
      algorithms are proposed that are able to estimate VOR parameters regardless of
      the presence of transients. Third, the new algorithms are applied to experimental
      data, and the results are compared with those from current algorithms. The
      results clearly show that the transient component can significantly alter the
      apparent VOR time constant, particularly when the reflex has been lesioned. The
      algorithms open new areas of research on the possible role of nystagmus in
      enhancing the compensatory function of the VOR.

PMID- 8274539
TI  - Modelling spatiotemporal properties of directionally sensitive multi-input single
      output systems.
AB  - The dynamics of directionally tuned linear multi-input single-output systems
      varies generally as a function of the spatial orientation of the inputs. A linear
      system receiving directionally specific inputs is represented by a linear
      combination of the respective input transfer functions. The input-output
      behaviour of such systems can be described by a vector transfer function which
      specifies the polarization directions of the system in real space. These
      directions, which can be either one (undirectional vector transfer function) or
      two (bidirectional vector transfer function) but never three, are obtained by
      computing the eigenvectors and eigenvalues of the system matrix that is defined
      by the gain and phase values of the system's response to harmonic stimulation
      directed along three orthogonal directions in space. The spatial tuning behaviour
      is determined by the quadratic form associated with the system matrix. Neuronal
      systems with bidirectional vector transfer functions process input information in
      a plane-specific way and exhibit novel characteristics, very much different from
      those of systems with unidirectional vector transfer functions.

PMID- 8274540
TI  - Adaptive orthogonalization of opponent-color signals.
AB  - This paper concerns the processing of the outputs of the two opponent-color
      mechanisms in the human visual system. We present experimental evidence that
      opponent-color signals interact after joint modulation even though they are
      essentially independent under neutral steady adaptation and after exclusive
      modulation of each mechanism. In addition, prolonged modulation linearizes the
      response function of each mechanism. The changes in interaction serve to
      orthogonalize opponent signals with respect to the adapting modulation, and the
      changes in response functions serve to equalize the relative frequencies of
      different levels of response to the adapting modulation. Adaptive
      orthogonalization reduces sensitivity to the adapting color direction, improves
      sensitivity to the orthogonal direction, and predicts shifts in color appearance.
      Response equalization enhances effective contrast and explains the difference
      between the effects of adaptation to uniform versus temporally or spatially
      modulated stimuli.

PMID- 8274541
TI  - A Bonhoeffer-van der Pol oscillator model of locked and non-locked behaviors of
      living pacemaker neurons.
AB  - A recent investigation of the influence of periodic inhibitory trains on a
      crayfish pacemaker neuron showed not only well-known locked periodic responses
      but also intermittent, messy, and hopping responses. This communication studies
      the responses of the Bonhoeffer-van der Pol (BVP) model with self-sustained
      oscillation when exposed to periodic pulse trains inputs. The analysis is similar
      to that used in crayfish and reveals interesting features, both comparable and
      complementary to those seen in the living preparation.

PMID- 8274542
TI  - Nonlinear terms produced by passing amplitude-modulated sinusoids through a hair
      cell transducer function.
AB  - We derive mathematically the output of Corey and Hudspeth's hair cell transducer
      function for the following cases: (1) the input is a single carrier whose output
      is modulated by the sum of two sinusoids; (2) the input is the sum of two
      carriers, each of which is amplitude-modulated by a single sinusoid. The
      theoretical results are similar to the results of an experiment in which field
      potentials were recorded from the human scalp while one ear was stimulated with
      auditory waveform (1) and with auditory waveform (2) of the cases above.

PMID- 8274543
TI  - Reverse correlation analysis of the stretch response of primary muscle spindle
      afferent fibers.
AB  - The nonlinear responses of deefferented primary muscle spindle afferent fibers to
      muscle stretching consisted of a train of action potentials which was analyzed
      when random changes in muscle length (band-limited gaussian white noise) were
      applied in cats. The upper cutoff frequency of the applied noise (the source
      stimulus) was varied between 1.6 and 570 Hz; the amplitude of the random input
      was varied between 0.002 and 1.2 mm. In a previous report the reverse correlation
      of 1st and 2nd order was studied for its ability to analyze data of a continuous
      input signal and pulsatile events in the output. Computations of the Wiener
      kernels h1 and h2 or their equivalents, the perispike averages of the 1st and 2nd
      order, were computed from the random stretch responses of muscle-spindle
      afferents. Then the 1st- and the 2nd-order predictions and the summation of both
      to random muscle stretch was estimated. A general finding was that the 1st-order
      component was approximately 10 times that of the 2nd-order component, when both
      were combined in approximation procedures to give the closest prediction of
      observed responses to random test stimuli. The approximation was poor when the
      source stimulus was less than 0.03 mm and improved when it was greater. With the
      increase in the upper cutoff frequency of the random source input, the
      approximation worsened continuously. Predictions to ramp-and-hold stimuli were
      computed, as well as responses to random stimulation. Limiting the upper cutoff
      frequency did not diminish the value of the techniques applied.

PMID- 8274544
TI  - Different ways of modeling spatial-frequency uncertainty in visual signal
      detection.
AB  - Inferior human signal-detection behavior compared with that of ideal observers
      has been explained by intrinsic uncertainty of the human observer with respect to
      certain signal parameters. One way to model this uncertainty is to assume that
      the observer simultaneously monitors multiple channels, corresponding to possible
      parameters. However, it is also conceivable to assume that an observer, uncertain
      about which channel to monitor, chooses a suboptimally tuned single filter.
      Finally, uncertainty may also cause the filter underlying a single channel to
      broaden. In this paper these different models are investigated with respect to
      spatial-frequency uncertainty for matched filters detecting Gabor signals. All
      three mechanisms predict a decrease in detection performance. However, it is
      shown that the resulting psychometric functions are different. While the slopes
      increase with uncertainty for the multiple-channel models, they decrease for a
      randomly chosen single channel. Broadening a single filter leads to parallel
      psychometric functions.

PMID- 8274545
TI  - Dynamic properties of cortical evoked (10 Hz) oscillations: theory and
      experiment.
AB  - Experiments probed the dynamic properties of stimulus-evoked (approximately 10
      Hz) oscillations in somatosensory cortex of anesthetized rats. Experimental
      paradigms and statistical time series analysis were based on theoretical ideas
      from a dynamic approach to temporal patterns of neuronal activity. From the
      results of a double-stimulus paradigm we conclude that the neuronal response
      contains two components with different dynamics and different coupling to the
      stimulus. Based on this result a quantitative dynamic model is derived, making
      use of normal form theory for bifurcating vector fields. The variables used are
      abstract, but measurable, dynamic components. The model parameters capture the
      dynamic properties of neuronal response and are related to experimental results.
      A structural interpretation of the model can be given in terms of the collective
      dynamics of neuronal groups, their mutual interaction, and their coupling to
      peripheral stimuli. The model predicts the stimulus-dependent lifetime of the
      oscillations as observed in experiment. We show that this prediction relies on
      the basic concept of dynamic bistability and does not depend on the modeling
      details.

PMID- 8274546
TI  - Simulated fovea of the human retina: psychophysical data confirming the model's
      ability to accurately predict resolution.
AB  - A series of psychophysical tests were designed to determine whether a computer
      simulation of the human retina could accurately predict the geometry of various
      stimuli that were optimally resolved for human foveal vision. Stimuli were used
      that were of the order of the grain of the cone mosaic, i.e., of the order of 2 x
      2'. In the first set of experiments, resolution was tested using a two-bar
      stimulus. In one experimental series the gap between the two bars was varied, and
      in a second series the gap was kept constant and the width of the bars varied. In
      a second set of experiments, various block letters and a number of series for
      each letter were used; in each experimental series a single parameter was
      systematically varied. The same stimuli were also used as inputs for the computer
      simulation. When proper controls were used, the psychophysical data and computer
      simulation gave remarkably comparable results. Care was taken to differentiate
      between simple detection of a pattern, and resolution, which involved proper
      identification of the image.

PMID- 8274547
TI  - Kinematic description of variability of fast movements: analytical and
      experimental approaches.
AB  - Analysis of variability of fast aimed movements predicts the properties of
      trajectory variance. The analysis is based on a kinematic model with nonlinear
      changes in "internal time". The purpose of the work was to identify different
      sources of variability and their influence on the trajectory variance. An
      analytical expression for the speed-accuracy trade-off is introduced. Experiments
      were performed with subjects making single-joint elbow flexion movements over
      different distances as fast as possible with their eyes closed to memorized
      targets. Standard deviation of movement trajectory increased during the first
      part of the movement and subsequently decreased. The variance peaked after the
      time of peak velocity, close to the time of peak deceleration. A dependence of
      the trajectory variance on movement distance (speed-accuracy trade-off) was seen
      during the movement (at times of peak velocity and peak deceleration) but not
      after the movement termination. We conclude that the previously reported drop in
      the variability of movement trajectory during the deceleration phase does not
      necessarily mean a compensation by the control system but may result from purely
      kinematic properties of the movement. The importance of the time of measurement
      for analysis of the speed-accuracy trade-offs is emphasized.

PMID- 8274548
TI  - Optimization by hierarchical mutant production.
AB  - Inspired by the successful description of the first steps of molecular evolution
      by the quasispecies theory and the successful application of quasispecies-like
      algorithms to optimization problems, we propose a hierarchically organized
      algorithm. This new algorithm is able to solve a spin glass and a travelling
      salesman problem using only point mutations. Furthermore, it performs better
      under comparable circumstances than the ordinary quasispecies algorithm.
      Depending on the structure of the fitness landscape of the examined problem under
      consideration the hierarchically organized algorithm proves to be much more
      suitable than a simple quasispecies algorithm, especially in clustered
      landscapes. Tuning the error rates reveals the critical minimum copy fidelity
      necessary to guarantee optimization. We propose to incorporate hierarchical
      concepts into optimization algorithms inspired by biological evolution, such a
      genetic algorithms.

PMID- 8274549
TI  - A dynamical neural network model for motor cortical activity during movement:
      population coding of movement trajectories.
AB  - As a dynamical model for motor cortical activity during hand movement we consider
      an artificial neural network that consists of extensively interconnected neuron
      like units and performs the neuronal population vector operations. Local
      geometrical parameters of a desired curve are introduced into the network as an
      external input. The output of the model is a time-dependent direction and length
      of the neuronal population vector which is calculated as a sum of the activity of
      directionally tuned neurons in the ensemble. The main feature of the model is
      that dynamical behavior of the neuronal population vector is the result of
      connections between directionally tuned neurons rather than being imposed
      externally. The dynamics is governed by a system of coupled nonlinear
      differential equations. Connections between neurons are assigned in the simplest
      and most common way so as to fulfill basic requirements stemming from
      experimental findings concerning the directional tuning of individual neurons and
      the stabilization of the neuronal population vector, as well as from previous
      theoretical studies. The dynamical behavior of the model reveals a close
      similarity with the experimentally observed dynamics of the neuronal population
      vector. Specifically, in the framework of the model it is possible to describe a
      geometrical curve in terms of the time series of the population vector. A
      correlation between the dynamical behavior of the direction and the length of the
      population vector entails a dependence of the "neural velocity" on the curvature
      of the tracing trajectory that corresponds well to the experimentally measured
      covariation between tangential velocity and curvature in drawing tasks.

PMID- 8274550
TI  - Antibiotics in abdominal surgery: the less the better.

PMID- 8274551
TI  - Laparoscopy in the diagnosis and treatment of acute abdominal conditions.
      Clinical review.

PMID- 8274552
TI  - A comparison between scalpel and electrocautery in modified radical mastectomy.
AB  - OBJECTIVE: To compare the effects of a conventional cold scalpel and
      electrocautery in modified radical mastectomy. DESIGN: A non-randomised
      controlled trial. SETTING: Teaching hospital in Southern Taiwan. SUBJECTS: 101
      consecutive patients with primary breast cancer who underwent modified radical
      mastectomy between July 1987 and June 1989. INTERVENTIONS: The 44 patients during
      the first year were allocated to have skin flaps fashioned conventionally with a
      cold scalpel and the 57 patients during the second year, by electrocautery. MAIN
      OUTCOME MEASURES: Morbidity and mortality among the 101 patients who underwent
      modified radical mastectomy. RESULTS: The groups were comparable in regard to
      age, menopause, cancer stage, weight of specimen and histological type of cancer.
      The mean blood loss was 567 ml when scalpel was used and 150 ml when
      electrocautery was used (p < 0.001). The postoperative fall in packed cell volume
      was significantly greater in the scalpel group (0.75 [0.26] compared with 0.28
      [0.15], p < 0.001) and more patients in this group required transfusion (9
      compared with 0, p < 0.01). There were no deaths in either group. There were no
      significant differences in operation time, total post-operative Hemovac drainage,
      postoperative hospital stay, the number of lymph nodes removed, the number of
      metastatic lymph nodes, and postoperative complications between the groups.
      CONCLUSION: Electrocautery is a safe, convenient and rational method for
      constructing skin flaps in modified radical mastectomy, and patients do not need
      blood transfusions.

PMID- 8274553
TI  - Expansion pattern and risk of rupture of abdominal aortic aneurysms that were not
      operated on.
AB  - OBJECTIVE: To analyse the outcome of selective management of patients with
      abdominal aortic aneurysms, the expansion patterns of the aneurysms, and the
      factors that influenced the rate of rupture. DESIGN: Retrospective study.
      SETTING: Malmo General Hospital, Lund University, Malmo, Sweden. SUBJECTS: 155
      patients (96 men and 59 women) with abdominal aortic aneurysms who were not
      selected for operation for whatever reason were included in the study immediately
      after their first ultrasound scan. MAIN OUTCOME MEASURES: Mortality, expansion
      rate (mm/year) measured on ultrasound scan, and rate of rupture of aneurysm.
      RESULTS: Median aneurysmal diameter was 40 mm (range 20-80), and length (n = 106)
      70 (range 28-140). The patients were followed up for a median of 3.4 years (range
      0-10.2). A total of 107 patients died and in 21 the aneurysms ruptured (4 were
      operated on and survived). Thirteen patients were re-evaluated and operated on
      electively. Ultrasonography was repeated in 98 patients, the median expansion
      rates (mm/year) were 3.1 (diameter) and 1.9 (length). There was a significant
      linear relationship between initial size (diameter and length) and rate of
      expansion of diameter. The risk of rupture was greater in larger aneurysms that
      were expanding more quickly. The cumulative mortality was not affected by the 21
      aneurysms that ruptured. CONCLUSION: Selective management of patients with aortic
      aneurysms is justified.

PMID- 8274554
TI  - Changes in the number of lower limb amputations during a period of increasing
      vascular surgical activity. Results of a nation-wide study, Denmark, 1977-1990.
AB  - OBJECTIVE: To find out if the number of lower limb amputations for peripheral
      occlusive arterial disease increased during the period of increased vascular
      surgical activity 1977-1990. DESIGN: Retrospective review of a database covering
      all admissions to Danish hospitals. SUBJECTS: All patients admitted to Danish
      hospitals with peripheral occlusive disease during the period 1977-1990. MAIN
      OUTCOME MEASURES: Numbers, and age and sex specific incidence rates for
      admission, arterial reconstruction and amputation. RESULTS: The number of
      admissions during which arterial reconstruction for OAD was done increased from
      963 in 1977 to 2311 in 1990 (p < 0.001). The number of admissions during which a
      diagnosis of OAD was made and an amputation done increased from 1290 in 1977 to a
      maximum of 1609 in 1983 (p < 0.001). The number remained nearly constant in the
      mid-1980s but decreased during last part of the period to 1181 in 1990 (p <
      0.001). CONCLUSION: The reduction in the number of amputations may indicate that
      vascular surgery even on a national scale is effective in preventing amputations
      for OAD.

PMID- 8274555
TI  - Concentrations of cytokines in peritoneal fluid after abdominal surgery.
AB  - OBJECTIVE: To assess the role of concentrations of cytokines in peritoneal fluid
      in estimating the severity of the host's response to the stress of abdominal
      operations. DESIGN: Prospective study. SETTING: University hospital, Japan.
      SUBJECT: 49 patients who underwent various abdominal operations. Main outcome
      measures--Correlations between concentrations of tumor necrosis factor-alpha (TNF
      alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) in peritoneal
      fluid measured on the first postoperative day on the one hand, and peritoneal
      bacterial count, length of operation, and operative blood loss, on the other.
      RESULTS: The concentrations of all three peritoneal cytokines correlated
      significantly with length of operation; those of TNF-alpha and IL-1 beta also
      correlated significantly with peritoneal bacterial count, and that of IL-1 beta
      with operative blood loss. There were significant correlations between the
      concentrations of the three cytokines. CONCLUSION: These correlations suggest
      that monitoring of the peritoneal concentrations of TNF-alpha, IL-1 beta, and IL
      6 may be helpful in estimating the severity of stress caused by abdominal
      operations.

PMID- 8274556
TI  - Risk factors associated with inguinal hernias: a case control study.
AB  - OBJECTIVES: To assess reported risk factors for the development of inguinal
      hernias, to develop a method of quantifying physical effort, and to correlate
      them. DESIGN: Case control study. SETTING: District hospital, Valencia, Spain.
      SUBJECTS: 290 selected patients who had undergone inguinal hernia repair, and 290
      age and sex matched controls. INTERVENTIONS: Each patient was interviewed and
      data collected on a specially designed questionnaire, and an "effort score"
      calculated. MAIN OUTCOME MEASURES: Incidence of specified risk factors. RESULTS:
      The only significant risk factor was physical effort (lifting heavy objects
      repeatedly over long periods of time), relative risk 2.92, 95% confidence
      interval 2.11 to 4.04. In addition, there were significant differences between
      index cases and controls in standard of education (p < 0.001), consumption of
      alcohol (p = 0.02), chronic cough (p < 0.001), net monthly income (p = 0.04), and
      amount of physical effort expended (p < 0.001). Patients with indirect hernias
      expended significantly more physical effort and were both heavier and taller, and
      patients with femoral hernias waited significantly longer than the others before
      having their hernias repaired. CONCLUSION: Inguinal hernias are associated with
      the expenditure of a considerable amount of physical effort, and are commoner
      among younger, poorly educated manual workers.

PMID- 8274557
TI  - Swenson's operation for neonatal Hirschsprung's disease.
AB  - OBJECTIVE: To describe our experience with Swenson's operation for Hirschsprung's
      disease done during the neonatal period. DESIGN: Retrospective study. SETTING:
      University department of paediatric surgery. SUBJECTS: 10 Neonates with
      Hirschsprung's disease. INTERVENTIONS: Rectosigmoidectomy and pull through
      (Swenson's operation), with covering transverse colostomy. MAIN OUTCOME MEASURES:
      Mortality, morbidity, and continence. RESULTS: The median age at definitive
      operation was 25 days (range 15-35). There was one late death three weeks after
      discharge from hospital of respiratory and cardiac failure. Two patients
      presented with caecal perforation and two with intestinal obstruction; in all
      four Hirschsprung's disease was diagnosed on frozen section, a transverse
      colostomy was done, and the Swenson's operation was done electively. The other
      six were diagnosed by barium enema examination and biopsy, and underwent total
      bowel irrigation followed by Swenson's operation and transverse colostomy. The
      colostomies were closed three to four weeks later. There were no postoperative
      complications. All nine surviving patients were continent (3-4 stools/day), at a
      mean (SD) follow up of 21 (5) months. CONCLUSION: With the current high standards
      of anaesthesia and neonatal intensive care, and an experienced surgeon, Swenson's
      operation for neonatal Hirschsprung's disease is safe and the procedure of choice
      for this condition.

PMID- 8274558
TI  - Proximal gastrectomy reconstructed by interposition of a jejunal pouch. Surgical
      technique.

PMID- 8274559
TI  - Stylet with a curved tip to facilitate introduction of new Tenckhoff catheters
      and reposition of displaced ones. Surgical technique.

PMID- 8274560
TI  - Cystic abdominal lymphangioma in children. Case report.

PMID- 8274561
TI  - Primary hydatid cyst of the breast. Case report.

PMID- 8274562
TI  - Subcutaneous lateral disruption of the abdominal wall with intestinal prolapse
      caused by a seat belt injury. Case report.

PMID- 8274563
TI  - Save the appendix: a useful conduit for reconstructive surgery.

PMID- 8274564
TI  - Liz's two hats. Interview by Darlene Small.

PMID- 8274565
TI  - Quality improvement and enterprise: working together in a hospital environment.

PMID- 8274566
TI  - Standards in action: supporting the advocacy role.

PMID- 8274567
TI  - Organizational downsizing: a health care trend of the '90s.

PMID- 8274568
TI  - We all have a choice.

PMID- 8274569
TI  - Nurses helping nurses.

PMID- 8274570
TI  - Have nurses become too task oriented?

PMID- 8274571
TI  - Try on someone else's shoes for a change.

PMID- 8274572
TI  - Physicians peer review. Values and inadequacies in monitoring quality of care.

PMID- 8274573
TI  - Feasting on simplicity.

PMID- 8274574
TI  - Avoid the risk of practicing law without a license.

PMID- 8274575
TI  - Expert affidavits and LNCs.

PMID- 8274576
TI  - Heterophobia: horror feminae and horror viri.

PMID- 8274577
TI  - Methylphenidate increases thought disorder in recent onset schizophrenics, but
      not in normal controls.
AB  - The effects of apomorphine and methylphenidate on thought disorder, as measured
      by the Thought Disorder Index, in schizophrenic patients and in normal controls
      were evaluated. Methylphenidate, but not apomorphine, increased thought disorder
      in patients. Neither drug significantly increased thought disorder in controls.

PMID- 8274578
TI  - CSF diazepam binding inhibitor and schizophrenia: clinical and biochemical
      relationships.
AB  - Diazepam-binding inhibitor (DBI) is a 9-kD neuropeptide that interacts with the
      benzodiazepine (BZD) binding sites of the neuronal gamma-aminobutyric acid type A
      (GABAA) receptor and with the glial mitochondrial BZD receptor (MBR). We explored
      the involvement of CSF DBI-LI in schizophrenia, based on the potential role of
      GABA in the negative symptoms associated with schizophrenia, the relationship of
      its receptors with dopamine and norepinephrine release, and the proposed
      therapeutic efficacy of BZDs in schizophrenia. Clinical data, CSF DBI-LI and CSF
      monoamine measures were obtained in 65 drug-free male chronic (DSM-IIIR)
      schizophrenic patients, 53 of whom were also tested prior to haloperidol
      withdrawal. Following haloperidol withdrawal, CSF DBI-LI increased significantly.
      Drug-free CSF DBI-LI did not correlate with CSF monoamines. CSF DBI-LI was
      significantly higher in paranoid compared to chronic undifferentiated
      schizophrenic patients. The data suggest that DBI may have a symptom modulatory
      rather than an etiological role in schizophrenia.

PMID- 8274579
TI  - Plasma homovanillic acid in neuroleptic responsive and nonresponsive
      schizophrenics.
AB  - Changes in plasma homovanillic acid (HVA) were investigated in neuroleptic
      responsive and nonresponsive schizophrenics in order to delineate parameters of
      dopamine regulation, which may underlie differences in neuroleptic responsivity.
      Nineteen schizophrenics were treated with haloperidol for 6 weeks. HVA was
      sampled at baseline, 24 hr after initial neuroleptic dose, and after 6 weeks of
      treatment. Subjects were pretreated with debrisoquin in order to reduce the
      peripheral production of HVA. The responders had an initial rise in HVA at 24 hr
      after first neuroleptic dose, followed by a decline back to baseline over the 6
      weeks of treatment. The nonresponders' HVA failed to rise at 24 hr after first
      neuroleptic dose. At 6 weeks of treatment their HVA had fallen to significantly
      below baseline. Thus, a rise in HVA 24 hr after the first dose of neuroleptic
      predicted treatment response; a fall in HVA at 6 weeks to below pretreatment
      values was associated with neuroleptic nonresponse.

PMID- 8274580
TI  - Significant reductions in synapsin but not synaptophysin specific activity in the
      brains of some schizophrenics.
AB  - The levels of the synaptic vesicle-associated proteins, synapsin and
      synaptophysin, were examined in human postmortem hippocampus from the brains of
      schizophrenics and age-matched controls using a quantitative western blot
      analysis. The schizophrenic samples had significantly lower levels of synapsin I
      than controls. In individual data, five of the seven schizophrenic samples had
      extremely low levels of synapsin, whereas two of the schizophrenic samples had
      normal levels of synapsin. This deficit in synapsin does not appear to be due to
      some non-specific neuronal loss as the levels of the other synaptic vesicle
      marker, synaptophysin, were near normal in all seven schizophrenics. Given that
      synapsin is thought to regulate neurotransmitter release, it is possible that
      this deficit in synapsin could result in abnormal processing of neuronal
      information as is seen in various sensory processing abnormalities associated
      with schizophrenia.

PMID- 8274581
TI  - Effects of clozapine on hematopoiesis and the cytokine system.
AB  - Using a bioassay for hematopoietic progenitor cells we looked for mechanisms
      causing clozapine induced neutropenia and agranulocytosis. Micro-agar-cultures of
      normal peripheral blood mononuclear cells (MNC) of eight patients currently
      treated with clozapine and of eight probands not receiving any kind of
      pharmacological treatment were incubated with increasing concentrations of
      clozapine (0, 7.5, 15, 30 micrograms/ml). Erythropoiesis and megakaryopoiesis
      were totally unaffected by clozapine. A biologically relevant suppression of
      granulopoiesis (CFU-GM) could only be shown in cultures incubated with 30
      micrograms/ml clozapine. Cytokine analysis presented a strictly dose-dependent
      suppression of GM-CSF and neopterin release in all cultures. There was no
      difference between patients and controls at any clozapine concentration. The data
      support a possible role for cytokines as one mediator of the agranulocytosis
      producing effects of clozapine.

PMID- 8274582
TI  - Treatment with carbamazepine may enhance alpha 2-noradrenergic autoreceptor
      sensitivity.
AB  - Chronic, not acute treatment with carbamazepine enhanced the hypothermic response
      to a dose of clonidine thought to exert its predominant effect on the presynaptic
      alpha 2-autoreceptor. This response was markedly elevated both during the course
      of and 10 days after the discontinuation of treatment with carbamazepine.
      Sensitivity to clonidine returned to baseline 10 to 21 days after the
      discontinuation of treatment. Carbamazepine is the first treatment for the
      disorders of mood that has been demonstrated to enhance a physiological response
      to clonidine. The authors discuss the theoretical relationship between increased
      sensitivity of the presynaptic alpha 2-autoreceptor and the usefulness of
      carbamazepine in the treatment of bipolar disorder.

PMID- 8274583
TI  - Noradrenergic response to intravenous yohimbine in patients with depression and
      comorbidity of depression and panic.
AB  - Adrenergic response following infusions of yohimbine or normal saline was
      evaluated in 9 control subjects, 8 patients suffering from a major depressive
      episode (MDE), and 12 patients suffering from concurrent MDE and panic disorder
      (MDE + P). Blood was drawn at -20, 0, 5, 10, 20, 45, and 90 min following the
      infusions, and assayed for norepinephrine (NE) and 3-methoxy-4-hydroxy-phenyl
      glycol (MHPG). Although the patient groups exhibited higher baseline NE
      concentrations, and a greater NE area under the plasma concentration versus time
      curve (AUC0-90) during the yohimbine infusion, the differences were not
      statistically significant. Baseline NE was significantly correlated with the NE
      AUC0-90 in all three groups, suggesting that, although the NE system may be
      dysregulated in the MDE and MDE + P patients, the NE system still appears to
      respond somewhat predictably following a challenge, even though the actual
      magnitude of response may vary.

PMID- 8274584
TI  - Changes in urinary MHPG during treatment of depression with imipramine.

PMID- 8274585
TI  - Elevated intracellular calcium levels after 5-HT2 receptor stimulation in
      platelets of depressed patients.

PMID- 8274587
TI  - A biological difference between panic disorder and generalized anxiety disorder.

PMID- 8274586
TI  - Response to SSRI antidepressants correlates with reduction in plasma HVA: pilot
      study.

PMID- 8274588
TI  - Withdrawal from chronic cocaine enhances behavioral sensitivity to the 5-HT2/1C
      agonist DOI.

PMID- 8274589
TI  - Changes in regional cerebral blood flow in patients with anorexia nervosa
      detected through single photon emission tomography imaging.

PMID- 8274590
TI  - Linkage of a normal personality trait to the color-blindness gene: preliminary
      evidence.

PMID- 8274591
TI  - Psychotic patients with increased plasma HVA and MHPG or increased HVA alone.

PMID- 8274592
TI  - Melatonin and jet lag: treatment schedule.

PMID- 8274593
TI  - Fluvoxamine treatment of dementia: tryptophan levels.

PMID- 8274594
TI  - History of opportunistic infection in the immunocompromised host.

PMID- 8274595
TI  - The changing epidemiology of infections at cancer hospitals.
AB  - Intensive chemotherapy regimens, widespread prophylactic and therapeutic
      administration of antibiotics, reliance on intravascular catheters, increased use
      of immunomodulators, and increased outpatient management have altered the
      epidemiology of infections in patients with neoplastic disease. At many centers,
      bacteremias due to gram-positive organisms have replaced bacteremias due to gram
      negative organisms as the most frequent infections in patients with cancer.
      Isolation of gram-negative bacilli other than Enterobacteriaceae and Pseudomonas
      aeruginosa has increased in frequency, and these organisms have become important
      pathogens. Fungal infections have become a leading cause of morbidity and
      mortality, and nosocomial fungemias have become more common than nosocomial
      bacteremias due to gram-negative bacilli in some centers. Mycobacterium
      tuberculosis, Pneumocystis carinii, and rubeola virus have reemerged as disease
      causing entities in patients with cancer. Multiresistant organisms have developed
      over the past decade. Anticipated trends in infections in patients with cancer
      also are discussed.

PMID- 8274596
TI  - AIDS in the developing world: an epidemiologic overview.
AB  - The pandemic of human immunodeficiency virus (HIV) infection is rapidly becoming
      a tropical disease. Sub-Saharan Africa alone currently accounts for approximately
      60% of the estimated > 11 million infections worldwide. In Africa the virus is
      transmitted heterosexually and in many areas is now widely dispersed in the
      general population. Spread of HIV in Asia has been more recent, with current
      estimates of 2 million infections, but has been very rapid in South and Southeast
      Asia. In Thailand extensive transmission of the virus has occurred over the last
      5 years. Initially, infections were seen in users of intravenous drugs and in
      commercial sex workers; now, however, HIV has spread to the general population.
      Recent, although incomplete, data from India suggest an epidemic curve
      reminiscent of the early epidemic in Africa and Thailand. With this rapid spread
      of the infection, there may be as many as 26 million infections--most in
      developing countries--by the year 2000.

PMID- 8274597
TI  - AIDS in the Republic of China, 1992.
AB  - From May 1985 to December 1992, a total of 5,931,032 serum samples from eight
      population groups were tested for antibody to human immunodeficiency virus type 1
      (HIV). Mandatory testing is carried out for blood donors, military recruits,
      immigrants, and prisoners. The other population groups were tested anonymously
      with consent. A total of 407 samples were seropositive. Of those HIV carriers, 63
      developed AIDS: 37 were homosexuals, 6 were hemophiliacs, 1 was an intravenous
      drug user, 15 were heterosexuals, and 4 had no known risk factors. Although the
      prevalence of HIV infection and AIDS in Taiwan has remained low, the increase
      since 1988 has been rapid. Before 1987, all of the 48 persons with HIV infection
      were homosexuals or hemophiliacs. Thereafter, the risk groups diversified, with
      the main group shifting from homosexuals to heterosexuals and the number of
      intravenous drug users surpassing the number of hemophiliacs. Among the 63
      patients with AIDS, 59 were male and only 4 were female; 53 have died (3
      committed suicide).

PMID- 8274598
TI  - AIDS in Haiti: 1982-1992.
AB  - Haiti was one of the first countries where AIDS was recognized, a burden that led
      to the stigmatization of an entire nation resulting in serious long-term
      economic, social, and psychological consequences. Sixty percent of urban hospital
      beds are now occupied by patients infected with human immunodeficiency virus
      (HIV). AIDS is the leading cause of death in sexually active adults and
      increasingly has become a disease of women and children. AIDS threatens to
      reverse the decrease in infant mortality achieved during the past decade. In
      spite of educational efforts, the "silent epidemic" continues in all parts of the
      country and within all strata of society. The current HIV seroprevalence is 10%
      in urban areas and 5% in rural areas. AIDS is known but not understood;
      counseling modifies behavior in only 10%-20% of at-risk persons. This distressing
      situation is likely to worsen in view of the ongoing political crisis since
      almost all AIDS-education programs are dependent on foreign support.

PMID- 8274599
TI  - Use and misuse of antibiotics in Latin America.
AB  - Some common characteristics that distinguish antibiotic use in Latin America are
      a high incidence of infections that are treatable with antibiotics, extensive use
      and frequent misuse of antibiotics, and frequent self-medication and
      nonprofessional prescription in the outpatient setting. Community-acquired
      organisms are generally more antibiotic-resistant in Latin America than in more
      industrialized countries. Antibiotics also are used extensively in hospitals,
      largely for surgical prophylaxis and for nosocomial infections, which occur more
      frequently (in 15%-20%) in hospitalized patients. Prophylactic use of antibiotics
      is largely inappropriate--i.e., indiscriminate, inopportune, and prolonged. A
      frequent outcome of this inappropriate use is the occurrence of nosocomial
      infections due to strains that are much more drug resistant than those
      encountered in industrialized countries. The great number of pharmaceutical
      products available, and the lack of stringent policies regarding drug sales and
      advertising often result in pressure to prescribe and in confusion not only among
      the public at large but among physicians themselves. Coordinated efforts to
      educate health care professionals, campaigns against self-medication, stricter
      rules for drug sales and advertising, and restricted use of certain antibiotics
      in hospitals may contribute to rational antibiotic use.

PMID- 8274600
TI  - Prevention of infections in patients with neoplastic disease: use of a historical
      model for developmental strategies.
AB  - Infections associated with neoplastic disease and its treatment are well
      described. Associations between specific infections and particular immune defects
      have also been defined. Despite the awareness that certain patient populations
      are at risk, potential prophylactic regimens for many of these infections have
      not been studied. The development of isoniazid for the prevention of tuberculosis
      is reviewed. The requirements for the study of prophylactic antibiotics in
      patients with neoplastic disease are discussed based on this example. Specific
      infections associated with neoplastic disease are suggested as candidates for
      multicenter controlled trials of prophylactic regimens.

PMID- 8274601
TI  - Prevention of infections in the neutropenic patient.
AB  - Infections are still a frequent cause of morbidity in patients with hematologic
      malignancies. Until 10 years ago the microorganisms most frequently encountered
      were aerobic gram-negative bacilli, which in many centers were responsible for,
      on average, one infection per neutropenic period. Many different approaches to
      the prevention of these infections have been designed. Patients have been kept in
      strict isolation and given broad-spectrum antibiotics prophylactically. This
      approach has led to a decrease in the incidence of infections in these patients,
      but compliance and emergence of resistance have been important limiting factors.
      The rationale of selective decontamination with trimethoprim-sulfamethoxazole or
      quinolones was that the elimination of potentially pathogenic aerobic gram
      negative bacilli from the gastrointestinal tract would prevent colonization and
      subsequent infection. The use of these antibiotics has led to a shift in the
      spectrum of infections. Infections due to gram-negative bacilli have been
      virtually eliminated, but the number of infections caused by gram-positive
      bacteria is rapidly increasing; however, the latter infections are most often
      only minor. In some centers quinolones are now used together with agents active
      against these gram-positive bacteria. The approach of selective decontamination
      has not led to fewer febrile episodes or to a lower mortality in neutropenic
      patients. Future studies should be directed towards identifying the cause of
      febrile episodes and the epidemiology of gram-positive bacterial infections.

PMID- 8274603
TI  - Prevention of infection in patients with B cell defects: focus on intravenous
      immunoglobulin.
AB  - Data with regard to B lymphocyte defects in patients with nonhematologic
      malignancies are limited. The incidence of bacterial infections following
      cytotoxic chemotherapy and major surgery appears to be higher for some patients
      with malignancies, but the infecting organisms are different than those found in
      patients with primary antibody deficiency. An exception to this are bacterial
      infections associated with hematologic malignancies, which usually are due to
      encapsulated bacteria. Antibody replacement therapy with intravenous
      immunoglobulin may reduce the frequency of infections in patients with
      hematologic malignancies or in those who have received chemotherapy or undergone
      major surgery for other malignancies. Better definition of B lymphocyte defects
      and additional trials of intravenous immunoglobulin therapy to define its role,
      particularly in relation to other methods of reducing infections, such as
      antibiotic prophylaxis, are needed.

PMID- 8274602
TI  - Prevention of infections in patients with T cell defects.
AB  - Although no specific infection is limited entirely to hosts with T-lymphocyte
      defects, certain microbial organisms have an affinity for such individuals.
      Effective, safe, and feasible methods are available for the prevention of two of
      the major life-threatening infections in patients with T-lymphocyte defects,
      although none of these methods is ideal. Trimethoprim-sulfamethoxazole
      administered orally daily or thrice weekly is highly effective for the prevention
      of Pneumocystis carinii pneumonia. For patients who cannot tolerate this drug
      combination, monthly inhalation of aerosolized pentamidine is an alternative
      prophylactic approach. Additional drugs in clinical or preclinical trials offer
      promise for use in preventing this pneumonitis. Varicella is one of the most
      frequent serious viral infections in patients with cancer, especially children.
      Varicella-zoster immune globulin (VZIG) has proven effective in reducing the
      frequency of infection in exposed susceptible individuals; however, breakthrough
      infections are not uncommon. Of 358 children with acute lymphoblastic leukemia,
      62 received VZIG following exposure to varicella, and 16 (26%) of these had
      breakthrough varicella. A live attenuated varicella-zoster virus vaccine offers
      promise, especially for the universal immunization of individuals before
      immunocompromise occurs.

PMID- 8274604
TI  - Empirical antibiotic therapy for fever in neutropenic patients.
AB  - The necessity for administering empirical antibiotic therapy to febrile
      neutropenic patients has been well-established; however, no single regimen has
      been uniformly accepted. During the past decade, gram-positive organisms, often
      methicillin-resistant, have emerged as significant pathogens. The routine use of
      vancomycin may be appropriate at some institutions, but its widespread use may
      lead to resistance. The role of aminoglycosides as part of routine empirical
      regimens is controversial, and single extended-spectrum beta-lactam agents are
      often adequate therapy. Not all beta-lactam agents are equally effective, and
      some gram-negative pathogens, such as Xanthomonas maltophilia, are resistant to
      many of them. Pneumonia is frequent, the infecting pathogen is often
      undetermined, and therapy is unsatisfactory. Outpatient antibiotic therapy can be
      used in selected neutropenic patients. Empirical antibiotic regimens should be
      selected on the basis of knowledge about predominant pathogens and antibiotic
      susceptibilities at each institution as much as on the basis of studies from
      other institutions reported in the literature.

PMID- 8274605
TI  - Prevention and treatment of cytomegalovirus pneumonia in transplant recipients.
AB  - The prevention of cytomegalovirus (CMV) infection in individuals at the highest
      risk, such as CMV-seronegative recipients of allogeneic bone marrow transplants
      or of CMV-positive solid organ transplants, involves the use of blood products
      obtained from CMV-seronegative donors or the use of filtered blood products. In
      addition, the use of ganciclovir is becoming increasingly important as an early
      means of preventing serious disease. The options for use of ganciclovir include
      conventional prophylaxis early after engraftment or preemptive use after
      documented infection. Evidence is reviewed for selected use of this drug in only
      the highest-risk subjects to avoid unnecessary adverse effects. The optimal use
      of ganciclovir in specific patient groups needs to be evaluated, and general
      recommendations that fit all groups cannot be made at this time. Although the use
      of intravenous immunoglobulin (IVIG) in transplantation remains controversial,
      there is increasing evidence to support a recommendation of the use of IVIG as
      general support for the allogeneic bone marrow transplant recipient and of CMV
      antibody-enriched immunoglobulin in selected renal transplant recipients. For the
      treatment of CMV-associated pneumonitis, it is recommended that ganciclovir and
      IVIG be used in combination for the bone marrow transplant recipient and that
      ganciclovir be used with or without IVIG in patients in other transplantation
      groups.

PMID- 8274606
TI  - Cytokines as antimicrobial therapy for the T cell-deficient patient: prospects
      for treatment of nonviral opportunistic infections.
AB  - Patients rendered T cell-deficient by advanced disease due to human
      immunodeficiency virus, an underlying neoplastic disorder, or immunosuppressive
      therapy are vulnerable to a select group of opportunistic infections. These
      infections, which often fail to respond to conventional therapy, provide the
      clinical setting in which the efficacy of treatment with cytokines can be tested.
      Particularly pertinent cytokines are those that activate macrophages and
      monocytes or enhance T-cell function. Experimental observations and emerging data
      from patients with intact T-cell function suggest that treatment with at least
      three cytokines, interferon-gamma, interleukin-2, and granulocyte-macrophage
      colony-stimulating factor (GM-CSF) may be of benefit. Each of these cytokines is
      already in clinical use, and each has therapeutic potential in a variety of
      different infectious disease. Patients with infections caused by opportunistic
      intracellular pathogens appear to be the most appropriate candidates for
      adjunctive cytokine therapy.

PMID- 8274607
TI  - Pneumocystis carinii pneumonia in patients without AIDS.
AB  - In the 1980s, tens of thousands of cases of Pneumocystis carinii pneumonia (PCP)
      occurred in persons with AIDS, making it the most common opportunistic infection
      encountered in this patient population. Thus, the presentation and clinical
      course of PCP became well-known to many physicians. Overshadowed by this epidemic
      was the continued occurrence of PCP in persons not infected with the human
      immunodeficiency virus, most notably those receiving immunosuppressive therapy
      for neoplastic disease or other indications. A review from Memorial Sloan
      Kettering Cancer Center has demonstrated that, in addition to those patients
      previously defined as at risk--those with acute lymphocytic leukemia or
      allogeneic bone marrow transplantation--patients receiving corticosteroid therapy
      for a primary or metastatic brain neoplasm are at risk for PCP and should receive
      prophylaxis. Among patients with neoplastic disease, the disease may be more
      fulminant and the mortality rate higher--approaching 50% in most series. Wider
      use of prophylaxis should decrease the frequency of this disease, while prompt
      initiation of therapy in patients with a compatible syndrome should help to lower
      mortality rates.

PMID- 8274608
TI  - Toxoplasmosis in patients with cancer.
AB  - The unusual occurrence, protein manifestations, and often devastating
      consequences of toxoplasmosis in patients with cancer emphasize the need for
      clinical acumen in the diagnosis and management of this disorder. Toxoplasmosis
      in patients with cancer has most commonly been described in association with
      Hodgkin's disease. It has also been reported, usually in the setting of treatment
      with antineoplastic agents, in patients with other lymphoproliferative disorders,
      hematologic malignancies, and solid tumors. In this review, among patients for
      whom the diagnosis was made early enough to begin specific treatment, conditions
      of 68% improved; this finding was in marked contrast to the severe morbidity and
      mortality observed for untreated individuals. The high mortality in the untreated
      group reflects the general debilitation and severe immunocompromise of these
      patients. Therefore, although toxoplasmosis contributed to a poor prognosis, it
      was not necessarily always the proximate cause of death.

PMID- 8274609
TI  - Mycobacterial diseases and the compromised host.
AB  - Tuberculosis due to Mycobacterium tuberculosis and other mycobacteria should be
      considered in the diagnostic approach to febrile immunocompromised patients. In
      patients with AIDS, organisms of the Mycobacterium avium complex (MAC) are the
      most common bacterial causes of disseminated infection. Effective means of both
      treating and preventing disseminated MAC infections have been developed that use
      regimens including the new macrolides, aminoglycosides, and rifamycins.
      Antimicrobial agents active against M. tuberculosis are not usually active
      against MAC organisms, and the converse may also be true. With the advent of more
      cases of drug-resistant tuberculosis, however, the urgency regarding development
      of new therapeutic approaches for tuberculosis is widely appreciated. Research
      into the pathogenesis and treatment of infections due to M. tuberculosis and MAC,
      which has been much neglected, is likely to provide new knowledge that will
      benefit the clinical approach to all mycobacterial diseases.

PMID- 8274610
TI  - Drug-resistant tuberculosis.
AB  - Multidrug-resistant tuberculosis (MDRTB) is an iatrogenic disease that is
      emerging as a major infectious disease problem throughout the world. The AIDS
      pandemic, increased incidence of tuberculosis in populations with easy access to
      antituberculosis medications, the deterioration of the public health
      infrastructure, and inadequate training of health care providers in the
      epidemiology of tuberculosis are some of the factors contributing to the
      increased incidence of MDRTB. Mortality from MDRTB exceeds 80% in persons
      infected with human immunodeficiency virus (HIV) but is also high in patients
      free of HIV. The management of MDRTB is complicated by the lack of methods for
      rapid detection of resistant strains of Mycobacterium tuberculosis. The risk of
      infection among close contacts of patients with MDRTB, the probability of the
      development of active MDRTB after infection, and the likelihood of cure of MDRTB
      need to be determined quantitatively. Attributable risk estimates for factors
      associated with MDRTB should be calculated for each community as part of the
      strategies to prevent MDRTB. Issues regarding chemoprophylaxis in newly infected
      contacts of MDRTB cases remain unanswered. Basic research on the mechanisms of
      action of existing antituberculosis drugs may contribute to an understanding of
      the mechanism of resistance in M. tuberculosis. There is an urgent need to expand
      the scope of epidemiological, clinical, and laboratory research to address these
      problems.

PMID- 8274611
TI  - The diagnostic mycobacteriology laboratory of the 1990s.
AB  - The diagnostic mycobacterial laboratory of the 1990s must respond to a change in
      the clinical spectrum of mycobacterial infections brought about by an increase in
      the number of patients who are immunocompromised, are indigent, or have temporary
      or permanent implanted devices. Emerging pathogens such as Mycobacterium
      haemophilum and Mycobacterium genavense, multidrug-resistant strains of
      Mycobacterium tuberculosis, and catheter infections with rapidly growing
      mycobacteria are examples of new issues. Fortunately, new methods for detection
      and identification of microbes have been or are being developed. Procedures that,
      when applied directly to clinical specimens or actively growing cultures,
      dramatically reduce the time to diagnosis of mycobacterial infections include
      radiometric broth, lysis-centrifugation, and biphasic systems for specimen
      culture, and DNA probes, high-performance liquid chromatography, DNA
      hybridization, restriction fragment length polymorphism, and gene amplification
      for organism detection and identification. At present, in vitro antimicrobial
      susceptibility tests are most helpful in guiding treatment of infections caused
      by M. tuberculosis and rapidly growing mycobacteria.

PMID- 8274612
TI  - Severe candidal infections in neutropenic patients.
AB  - The incidence of candidal infections in patients with cancer is increasing, and
      drug-resistant fungi are being isolated more frequently. Diagnosis of
      hematogenously disseminated candidiasis remains difficult. Characteristic
      clinical presentations, such as endophthalmitis and chronic hematogenously
      disseminated candidiasis, are inconstant and may not develop until after
      neutrophil recovery. Blood cultures are insensitive for detecting candidemia.
      Growth of Candida species in even one blood culture is strongly suggestive of
      hematogenously disseminated candidiasis. Serological tests to diagnose this
      disease remain experimental. Whenever feasible, central venous catheters should
      be removed from patients with candidemia. Amphotericin B is the treatment of
      choice for acute and chronic hematogenously disseminated candidiasis. The roles
      of azoles and liposomal amphotericin B in treating these diseases are currently
      undefined. Prophylactic use of antifungal agents decreases the incidence of
      documented fungal infections in neutropenic patients but does not improve overall
      survival and may increase the likelihood of infections by resistant fungi.

PMID- 8274613
TI  - Prevention of invasive fungal infections in patients with neoplastic disease.
AB  - Invasive fungal infections are important causes of morbidity and mortality among
      patients with neoplastic diseases, particularly those with protracted
      granulocytopenia, those receiving corticosteroids, and those undergoing
      allogeneic bone marrow transplantation. These mycoses are often difficult to
      diagnose early, and their treatment is frequently unsuccessful. Antifungal
      compounds have been used in studies of a variety of preventive strategies
      including prophylaxis, early empirical therapy, empirical therapy, and secondary
      prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated
      the most promising activity in prevention of invasive candidiasis, particularly
      in adult allogeneic bone marrow transplant recipients. However, fluconazole does
      not have activity at currently approved dosages against Candida krusei,
      Torulopsis glabrata, and most filamentous fungi, including Aspergillus species.
      Empirically administered amphotericin B significantly decreases the frequency of
      invasive fungal infections in persistently or recurrently febrile
      granulocytopenic patients. The use of itraconazole for prevention of
      aspergillosis warrants study. The current lack of reliable preventive regimens
      against infections due to Aspergillus and against those due to several emerging
      fungal pathogens presents an ongoing challenge. The use of recombinant human
      cytokines, transfusion of effector cells, and administration of newer antifungal
      compounds are new potential modalities for prevention of invasive mycoses.

PMID- 8274614
TI  - Infections with Aspergillus species.
AB  - Invasive aspergillosis is a common infection in patients who are
      immunocompromised. The diagnosis of invasive aspergillosis is difficult in the
      absence of confirmation by tissue biopsy and histological studies. Therefore,
      recent advances that may be important for the development of highly sensitive and
      specific serodiagnostic tests for the early diagnosis of invasive aspergillosis
      are reviewed. The inability of the detection of antibody to Aspergillus to lead
      to early diagnosis of invasive aspergillosis also is emphasized. However,
      sensitive methods that reliably detect significant amounts of aspergillus antigen
      in body fluids of high-risk patients are currently being evaluated and may
      provide a noninvasive early diagnostic test that is both sensitive and specific.
      Also, current antifungal agents with anti-aspergillus activity that have
      potential as therapeutic or prophylactic agents are reviewed briefly.

PMID- 8274615
TI  - Emerging fungal pathogens in immunocompromised patients: classification,
      diagnosis, and management.
AB  - Fungi such as Fusarium species, Trichosporon species, Curvularia species, and
      Alternaria species previously were thought to represent contamination or harmless
      colonization when isolated from immunocompromised patients. More recently, the
      pathogenic role of these and other fungi has been clearly established. Three
      diverse groups of fungi are responsible for these emerging infections: the agents
      of phaeohyphomycosis and hyalohyphomycosis and certain yeasts. Reports of the
      emergence of these organisms as significant pathogens may be ascribed to
      increasing awareness by physicians and microbiologists, aggressive culture of
      patient specimens, increasingly cytotoxic chemotherapy, and selection of
      resistant organisms by the widespread empirical use of amphotericin B. Infections
      with these fungi tend to be disseminated and are frequently fatal in
      immunocompromised hosts. Treatment of these infections is not standardized.
      Experimental therapy in murine models of fungal infections suggests a role for
      newer agents, combination antifungal chemotherapy, and immunotherapy.

PMID- 8274616
TI  - Antifungal susceptibility testing of yeasts: a brief overview.
AB  - Antifungal susceptibility testing of yeasts has lacked reproducibility because of
      the absence of universally accepted guidelines. The major sources of variation in
      susceptibility testing have been attributed to the choice of medium and pH,
      inoculum preparation and size, incubation temperature and time, and end-point
      criteria. These parameters have been addressed by the National Committee for
      Clinical Laboratory Standards (NCCLS) Subcommittee on Antifungal Susceptibility
      Testing, and proposed guidelines have recently been published. Although major
      advances in antifungal susceptibility testing have been achieved, particularly
      through the efforts of the NCCLS subcommittee, the results of studies to date do
      not support a correlation between the results of in vitro susceptibility testing
      and in vivo response. Routine antifungal susceptibility testing of yeasts should
      therefore be discouraged until the methodology is standardized such that it
      predicts clinical outcome.

PMID- 8274617
TI  - New methods of delivery of amphotericin B.
AB  - Fungal infections continue to be a major problem in the management of
      immunocompromised patients. Despite its formidable toxicity and treatment
      failures, amphotericin B is still the drug of choice for most of these
      infections. One strategy for reducing the toxicity of amphotericin B and thus
      permitting administration of higher doses is that of using less toxic
      formulations. Entrapping amphotericin B into liposomes or binding it to other
      substances reduces its toxicity to host cells, whereas the selective binding of
      amphotericin B to ergosterol preserves its toxicity to fungal cells. Adding
      fungus-specific antibodies to such liposomes may further increase the efficiency
      of drug targeting. The initial unpublished data from controlled clinical trials
      of various liposomal preparations of amphotericin B are less encouraging than
      anticipated, but additional trials are needed for a proper evaluation. Another
      strategy for improving efficacy of amphotericin B is that of bringing it directly
      into contact with the body sites most likely to be infected. Intranasal delivery
      of amphotericin B for prevention of invasive aspergillosis has been evaluated in
      at least three different clinical trials with conflicting results; no controlled
      trials are available. Prophylactic administration of low doses of amphotericin B
      as an aerosol was the most effective of the regimens tested in an animal model of
      pulmonary aspergillosis and was also judged to be effective in a clinical trial
      using historical controls. Independent of the route of administration, in both an
      animal model was various clinical studies, early administration of amphotericin B
      was more effective than late administration.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274618
TI  - Therapy with antibody to tumor necrosis factor in sepsis.
AB  - Recent data indicate that proinflammatory cytokines mediate pathophysiological
      events during clinical sepsis. The cytokine tumor necrosis factor (TNF) has been
      closely associated with adverse outcome from sepsis, both in animal models and in
      the clinical setting. Accordingly, monoclonal antibodies with the capacity to
      neutralize TNF in vitro have been developed for evaluation as therapeutic agents
      in clinical sepsis. Preclinical studies in animal models of sepsis due to gram
      negative as well as to gram-positive bacteria suggest that monoclonal antibodies
      to TNF may have potential as a therapeutic agent. Clinical trials to test this
      hypothesis are under way.

PMID- 8274619
TI  - The economic impact and cost-effectiveness of monoclonal antibody therapy for
      sepsis.
AB  - Monoclonal antibodies directed against the endotoxins produced by gram-negative
      organisms have been developed for the treatment of patients with sepsis. Phase 3
      clinical trials in which two of these agents, E5 and HA-1A, have been evaluated
      have suggested possible benefit in terms of improved survival and reversal of
      organ dysfunction for certain subgroups. Since monoclonal antibodies are expected
      to be expensive, cost-effectiveness analysis is necessary to assess the joint
      clinical and economic impact. Cost-effectiveness studies based on the clinical
      data from these phase 3 trials have suggested that monoclonal antibodies may
      represent a cost-effective approach to the treatment of sepsis. However, an
      increase in the number of questions concerning the clinical efficacy of these
      agents and their ultimate impact on survival mandates the need for further
      clinical and economic investigation.

PMID- 8274620
TI  - Emerging antimicrobial resistance and the immunocompromised host.
AB  - Infections caused by gram-positive bacteria have become the most important cause
      of infectious morbidity among some groups of immunocompromised patients over the
      last decade. Among the gram-positive bacteria, the emerging problems of
      resistance to antimicrobial agents include the development of resistance to beta
      lactam and aminoglycoside drugs among the enterococci, making synergistic
      bactericidal therapy impossible; the continued spread of methicillin-resistant
      staphylococci; resistance to both vancomycin and teicoplanin among enterococci
      and staphylococci; the emergence of intrinsically vancomycin-resistant species as
      important pathogens; and resistance to the fluoroquinolones. It is unlikely that
      new therapeutic classes of antibacterial drugs will be released this decade.
      Therapeutic alternatives now include unusual combinations of antibiotics to which
      the strains may appear resistant but that exhibit synergistic activity, although
      this area has not yet been thoroughly explored. Therefore, control of emergence
      and spread of resistance through the more judicious use of existing agents, good
      infection control practices, and the use of imaginative combination therapy for
      those infected with resistant strains seem to be our best alternatives.

PMID- 8274621
TI  - Adjunctive therapy for bacterial meningitis: rationale for use, current status,
      and prospects for the future.
AB  - Despite the introduction of numerous therapeutic advances, the morbidity and
      mortality associated with bacterial meningitis remain significant. Research into
      the pathophysiology of bacterial meningitis has revealed that the inflammatory
      response resulting from bacterial invasion of the subarachnoid space is due in
      large part to the activity of host-derived mediators. This inflammatory response
      is ultimately responsible for the long-term neurological sequelae and death
      associated with bacterial meningitis. In vitro and in vivo models of bacterial
      meningitis have identified several points in the inflammatory cascade that may be
      amenable to therapeutic intervention. Numerous potential therapeutic agents that
      may limit inflammation of the subarachnoid space have been and are being
      developed, and trials in animal models and in humans are under way. The judicious
      use of safe and effective agents with demonstrated efficacy as adjuncts to
      bactericidal antimicrobial agents in the therapy for bacterial meningitis in
      humans may improve the prognosis of this disease.

PMID- 8274622
TI  - Role of intracellular Ca2+ in EDRF release in rat aorta.
AB  - In rings of rat aorta, cyclopiazonic acid (CPA), a selective inhibitor of the
      internal membrane Ca(2+)-pump ATPase, gradually initiated a concentration
      dependent contraction which was much less in endothelium-intact than in
      endothelium-denuded rings. In phenylephrine-precontracted rings with intact
      endothelium, CPA, like acetylcholine, produced endothelium-dependent relaxations
      in a concentration-dependent manner. These were nearly abolished by methylene
      blue (MB) or NG-nitro-L-arginine methylester (L-NAME). This inhibitory effect of
      L-NAME was reversed by L-arginine but not by D-arginine, indicating that CPA
      induced a release of endothelium-derived relaxing factor (EDRF) from endothelial
      cells leading to smooth muscle relaxation. Concentration-dependent relaxations
      induced by sodium nitroprusside, which is thought to act by releasing nitric
      oxide, were not inhibited by L-NAME, but were inhibited similarly by MB in
      endothelium-intact and -denuded rings. These results indicate that CPA causes
      EDRF-release from endothelial cells and support the recent hypothesis that
      release of intracellular Ca from stores is the initiating factor in EDRF release,
      possibly allowing ongoing Ca entry to sustain release.

PMID- 8274623
TI  - Contractile responses of caudal arteries from diabetic rats to adrenergic nerve
      stimulation.
AB  - The effect of 12-14 weeks streptozotocin-induced diabetes on contractile
      responses of the highly innervated caudal artery to adrenergic nerve stimulation
      was studied. The maximum contractile response and sensitivity (as reflected by
      the pD2 value) to noradrenaline (NA) was significantly greater in diabetic than
      in control caudal arteries. The maximum contractile response, but not
      sensitivity, to tyramine was significantly enhanced in diabetic compared with
      control caudal arteries when expressed as stress (mN/mm2), but not when expressed
      as a percentage of the maximum NA response obtained between the responses of
      control and diabetic caudal arteries to electrical field stimulation of
      adrenergic nerves, when expressed either as stress or as a percentage of the
      corresponding NA response. Pretreatment with phentolamine markedly inhibited the
      contractile responses to field stimulation of both diabetic and control caudal
      arteries, while 6-hydroxydopamine essentially abolished responses to electrical
      field stimulation and tyramine in both tissues. Finally, pretreatment with
      hydrocortisone, timolol, and desipramine increased sensitivity to NA in control
      and diabetic caudal arteries by a similar magnitude. Thus, the enhanced
      contractile responses of caudal arteries from diabetic rats to NA do not appear
      to be associated with the development of autonomic neuropathy.

PMID- 8274624
TI  - Lipid peroxidation and oxidative stress during acute allylamine-induced
      cardiovascular toxicity.
AB  - Allylamine is an aliphatic amine that causes vascular lesions in aorta and medium
      sized arteries. This primary amine has been shown to be metabolized to acrolein
      both in vivo and in vitro. Acrolein may cause allylamine's toxic effects, since
      it acts as a strong peroxidizing agent itself; in addition, deamination of
      allylamine is accompanied by production of hydrogen peroxide. To investigate the
      relative roles of oxidative stress and lipid peroxidation in allylamine
      intoxication, we conducted an acute in vivo time-course study following
      administration of allylamine (150 mg/kg) to rats by gavage. Animals were
      sacrificed at 1, 3 and 5 h after allylamine treatment, and subcellular fractions
      of aorta, epicardium and endocardium were assayed for enzymes of the oxidant
      defense system and thiol (-SH) status, capacity for lipid peroxidation, and .OH
      radical generation. Results suggest that in vivo treatment with allylamine causes
      preferential damage to aortic mitochondria. A marked depletion of total and free 
      SH content was found in aorta, epicardium and endocardium, with a striking
      increase in the formation of thiobarbiturate-reactive substance by aortic
      mitochondria at all time points. A significant increase in the capacity to
      generate .OH was found in aorta (with lesser increases in epicardium and
      endocardium) after allylamine treatment. Levels of defense system enzymes were
      not consistently altered, however. In a totally in vitro experiment, liposomes
      incubated with acrolein (0.2-2 mM) showed a proportional increase in lipid
      peroxidation of liposomal membrane. A likely basis of allylamine's cardiovascular
      toxicity is acrolein-induced lipid peroxidation, especially in mitochondria.

PMID- 8274625
TI  - Identification of a nonendothelial cell thromboxane-like constrictor response and
      its interaction with the renin-angiotensin system in the aorta of spontaneously
      hypertensive rats.
AB  - Aortic ring preparations from spontaneously hypertensive rats (SHR) and
      normotensive Wistar Kyoto (WKY) rats were treated with N omega-nitro-L-arginine
      (NOLA, 10(-4) M). This produced a sustained contraction in preparations from SHR
      but not WKY rats. A similar contraction in aortic ring preparations from the SHR
      was produced with methylene blue (10(-5) M) and NG-monomethyl-L-arginine (10(-5)
      M). The NOLA-induced contraction was reversed with indomethacin (8 x 10(-6) M),
      ridogrel (10(-5) M) and SQ 29548 (10(-6) M) thus confirming the involvement of
      thromboxane A2/prostaglandin H2 processes. Subsequent experiments demonstrated
      that the thromboxane-like contraction was not dependent upon the presence of
      endothelial cells and occurred in preparations from young, prehypertensive (5
      week) and older (17 week) SHRs. The thromboxane-like contraction was markedly
      suppressed with chronic captopril treatment and reinstated 4 weeks after
      withdrawal from captopril. The addition of saralasin (10(-6) M) or captopril (10(
      6) M) to aortic ring preparations did not suppress the thromboxane-like
      contractions. The foregoing findings support the presence of a nonendothelial
      cell thromboxane-like constrictor agent in the aorta of the SHR that is revealed
      after impairment of nitric oxide production. The activity of the thromboxane-like
      constrictor process is not tightly linked to prevailing blood pressure, but is
      reduced with chronic in vivo inhibition of the angiotensin-converting enzyme.

PMID- 8274626
TI  - Analysis of relaxation processes helps to define molecular states in biological
      systems.

PMID- 8274627
TI  - Filling the gaps in Ca2+ channel regulation.

PMID- 8274628
TI  - Calcium oscillations and waves: is the IP3R Ca2+ channel the culprit?

PMID- 8274629
TI  - Lipid molecular shape and high curvature structures.

PMID- 8274630
TI  - The effect of a variable dielectric coefficient and finite ion size on Poisson
      Boltzmann calculations of DNA-electrolyte systems.
AB  - The results of variable dielectric coefficient Poisson-Boltzmann calculations of
      the counter-ion concentration in the vicinity of an all-atom model of the B-form
      of DNA are presented with an emphasis on the importance of spatial variations in
      the dielectric properties of the solvent, particularly at the macro-ion-solvent
      interface. Calculations of the distribution of hard-sphere electrolyte ions of
      various dimensions are reported. The presence of a dielectric boundary
      significantly increases the magnitude of the electrostatic potential with a
      concomitant increase in the accumulation of small counter-ions in the groove
      regions of DNA. Because ions with radii greater than 2 A have restricted access
      to the minor groove, the effect there is less significant than it is within the
      major groove. Changes in the dielectric coefficient for the electrolyte solution,
      allowing variation from 10 to 25, 40, 60, and 78.5 within the first 7.4 A of the
      surface of DNA, substantially increases the calculated surface concentration of
      counter-ions of all sizes. A lower dielectric coefficient near the macro-ion
      surface also tends to increase the counter-ion density in regions where the
      electrostatic potential is more negative than -kT. Regardless of the choice of
      dielectric coefficient, the number of ions in regions where the electrostatic
      potential is less than -kT remains the same for 0.153 M added 1-1 monovalent
      electrolyte as for the case without added salt. The strong dependence of the
      calculated distribution of counter-ion density on the choice of dielectric
      coefficients representing the solvent continuum suggests that care must be taken
      to properly characterize the physical system when studying electrostatic
      properties using these methods.

PMID- 8274631
TI  - A novel method to study the electrodynamic behavior of actin filaments. Evidence
      for cable-like properties of actin.
AB  - Actin, one of the most abundant intracellular proteins, forms long linear
      polyelectrolytic polymers in solution. A novel technique to handle single actin
      filaments in solution was developed that allows the study of ionic currents
      elicited along the surface of electrically stimulated actin filaments. Electrical
      currents were observed about the polymer's surface under both high (100 mM KCl)
      and low (1 mM KCl) ionic strength conditions. The data are consistent with a
      dynamic behavior of the counterionic cloud surrounding the actin filaments that
      support ionic movements along their longitudinal axis upon electrical
      stimulation. Counterionic waves were highly nonlinear in nature and remained long
      after the electrical stimulation of the actin filaments ceased. In this report
      therefore, we demonstrate that actin filaments can function as biological
      "electrical wires" and can thus be conceptualized as nonlinear inhomogeneous
      transmission lines. This ability of actin filaments to conduct electrical signals
      may have important implications in the coupling of intracellular signals.

PMID- 8274632
TI  - Gating kinetics of the quisqualate-sensitive glutamate receptor of locust muscle
      studied using agonist concentration jumps and computer simulations.
AB  - Outside-out patches excised from extrajunctional membrane of locust muscle were
      subjected to "concentration jumps" of L-glutamate, using the liquid filament
      switch technique, to study channel opening and closing rates, desensitization
      onset, and recovery from desensitization of a quisqualate-sensitive glutamate
      receptor (qGluR). Based on data obtained from these experimental studies,
      computer modeling techniques have been used in an attempt to simulate the
      behavior of qGluR during a concentration jump of L-glutamate. A linear model with
      three closed states (one unliganded, one monoliganded, and one biliganded), one
      open state (binding two molecules of L-glutamate), and two desensitization states
      (the one monoliganded, the other biliganded) leading from the unliganded closed
      state simulated all of the experimentally observed behavior. The results are
      discussed in the context of previous equilibrium studies in which desensitization
      was inhibited with concanavalin A and for which a ten-state model was required to
      simulate the behavior of qGluR.

PMID- 8274633
TI  - Budding and fission of vesicles.
AB  - We report on budding and fission of protein-free vesicles swollen from a natural
      lipid mixture of bovine brain sphingomyelins. Budding was induced by increasing
      the area-to-volume ratio through heating. Morphological changes were monitored by
      phase contrast microscopy and correlated with the thermal behavior of the bilayer
      by differential scanning calorimetry. Freeze fracture electron microscopy
      revealed that budding and fission are not restricted to giant vesicles but also
      occur on length scales relevant for cellular processes. We also observed
      osmotically induced budding and fission in mixtures of dimyristoyl
      phosphatidylcholine with cholesterol. We find that these shape transitions are
      driven by liquid/gel domain formation and/or coupling of the spontaneous
      curvature of the membrane to the local lipid composition. Our results provide
      evidence that coat proteins are not necessary for budding and fission of
      vesicles. The physics of the lipid bilayer is rich enough to explain the observed
      behavior.

PMID- 8274635
TI  - Energy-minimized structures and packing states of a homologous series of mixed
      chain phosphatidylcholines: a molecular mechanics study on the diglyceride
      moieties.
AB  - Phosphatidylcholines or C(X):C(Y)PC, quantitatively the most abundant lipids in
      animal cell membranes, are structurally composed of two parts: a headgroup and a
      diglyceride. The diglyceride moiety consists of the glycerol backbone and two
      acyl chains. It is the wide diversity of the acyl chains, or the large variations
      in X and Y in C(X):C(Y)PC, that makes the family of phosphatidylcholines an
      extremely complex mixture of different molecular species. Since most of the
      physical properties of phospholipids with the same headgroup depend strongly on
      the structures of the lipid acyl chains, the energy-minimized structure and
      steric energy of each diglyceride moiety of a series of 14 molecular species of
      phosphatidylcholines with molecular weights identical to that of
      dimyristoylphosphatidylcholine without the headgroup are determined in this
      communication by molecular mechanics (MM) calculations. Results of two types of
      trans-bilayer dimer for each of the 14 molecular species of phosphatidylcholines
      are also presented; specifically, the dimeric structures are constructed
      initially based on the partially interdigitated and mixed interdigitated packing
      motifs followed subsequently by the energy-minimized refinement with MM
      calculations. Finally, tetramers with various structures to model the lateral
      lipid-lipid interactions in a lipid bilayer are considered. Results of laborious
      MM calculations show that saturated diacyl C(X):C(Y)PC with delta C/CL values
      greater than 0.41 prefer topologically to assemble into tetramers of the mixed
      interdigitated motif, and those with delta C/CL values less than 0.41 prefer to
      assemble into tetramers with a repertoire of the partially interdigitated motif.
      Here, delta C/CL, a lipid asymmetry parameter, is defined as the normalized acyl
      chain length difference between the sn-1 and sn-2 acyl chains for a C(X):C(Y)PC
      molecule; an increase in delta C/CL value is an indication of increasing
      asymmetry between the two lipid acyl chains. These computational results are in
      complete accord with the calorimetric data presented previously from this
      laboratory (H-n. Lin, Z-q. Wang, and C. Huang. 1991. Biochim. Biophys. Acta.
      1067:17-28).

PMID- 8274634
TI  - Effects of alcohol-induced lipid interdigitation on proton permeability in L
      alpha-dipalmitoylphosphatidylcholine vesicles.
AB  - 6-Carboxyfluorescein was employed to examine the effect of alcohol-induced lipid
      interdigitation on proton permeability in L-alpha-dipalmitoylphosphatidylcholine
      (DPPC) large unilamellar vesicles. Proton permeability was measured by monitoring
      the decrease of 6-carboxyfluorescein fluorescence after a pH gradient from 3.5
      (outside the vesicle) to 8.0 (inside the vesicle) was established. At 20 degrees
      C and below 1.2 M ethanol, the fluorescence decrease is best described by a
      single exponential function. Above 1.2 M ethanol, the intensity decrease is
      better described by a two-exponential decay law. Using the fitted rate constants
      and the vesicle radii determined from light-scattering measurements, the proton
      permeability coefficient, P, in DPPC vesicles was calculated as a function of
      ethanol concentration. At 20 degrees C, P increases monotonically with increasing
      ethanol content up to 1.0 M, followed by an abrupt increase at 1.2 M. The vesicle
      size also exhibits a sudden increase at around 1.2 M ethanol, which has been
      shown to result from vesicle aggregation rather than vesicle fusion. The abrupt
      increases in P and in vesicle size occur at the concentration region close to the
      critical ethanol concentration for the formation of the fully interdigitated gel
      state of DPPC. At 14 degrees C, the abrupt change in P shifts to 1.9-2.0 M
      ethanol, completely in accordance with the ethanol-temperature phase diagram of
      interdigitated DPPC. Effects of methanol and benzyl alcohol on lipid
      interdigitation have also been examined. At 20 degrees C, DPPC large unilamellar
      vesicles exhibit a dramatic change in P at 3 M methanol and at 40 mM benzyl
      alcohol. These concentrations come close to the critical methanol and benzyl
      alcohol concentrations for the formation of fully interdigitated DPPC structures
      determined previously by others. It can be concluded that proton permeability
      increases dramatically as DPPC is transformed from the noninterdigitated gel to
      the fully interdigitated gel state by high concentrations of alcohol. This marked
      increase in proton permeability can be attributed to the combined effect of the
      changes in membrane thickness and surface charge density, due to the ethanol
      induced lipid interdigitation. The possible effects of the increased proton
      permeability caused by ingested ethanol on gastric mucosal membranes are
      discussed.

PMID- 8274636
TI  - Support for the shape concept of lipid structure based on a headgroup volume
      approach.
AB  - Headgroup volumes of seven dioleoyl lipid species, calculated from covalent
      radii, are shown to correlate linearly (r = 0.95) with the ability of those
      lipids to alter the midpoint temperature of the lamellar to inverted hexagonal
      phase transition (L alpha-->HII) of a 95 mole fraction percent
      phosphatidylethanolamine matrix. The results illustrate the utility of the shape
      concept and basic considerations of headgroup volume as a predictive tool for the
      determination of lipid structure.

PMID- 8274637
TI  - Transient kinetics of the interaction of actin with myosin subfragment-1 in the
      absence of nucleotide.
AB  - The kinetics of the association of actin with myosin subfragment-1 (S1) has been
      studied by using S1 labeled at the sulfhydryl group SH1 with 5
      (iodoacetamido)fluorescein (S1-AF). Upon rapid mixing in a stopped-flow
      apparatus, the fluorescence intensity of the fluorescein moiety increased by 50%,
      followed by a slower increase that was well resolved. This slow phase of the
      fluorescence change could not be fitted to either a monoexponential or a
      biexponential function, but it could be fitted to a sum of three exponential
      terms yielding three observed first-order rate constants (lambda i). The
      dissociation of acto.-(S1-AF) was studied by displacement of S1-AF from the
      complex with native S1. The dissociation kinetics was characterized by a single
      rate constant (approximately 0.012 s-1 at 20 degrees C), and this constant was
      independent of S1 concentration. Together with previous equilibrium data that
      were obtained under identified conditions for formation of acto-subfragment-1
      (Lin, S.-H., and H. C. Cheung. 1991. Biochemistry. 30:4317-4323), a six-state two
      pathway model is proposed as a minimum kinetic scheme for formation of rigor
      acto.S1. In this model, unbound subfragment-1 exists in two conformational states
      (S1' and S1) which are in equilibrium with each other, one corresponding to the
      previously established low-temperature state and the other to the high
      temperature state. Each subfragment-1 state can interact with actin to form a
      collision complex, followed by two isomerizations to form two acto-subfragment-1
      states (A.S1' and A.S1). Both isomerizations were visible in stopped-flow
      experiments. Two special cases of the model were considered: 1) a rapid pre
      equilibration of the initial collision complex with actin and S1, and 2) trace
      accumulation of the collision complex. The first case required that the three
      combinations of the three observed rate constants be independent of actin
      concentration. The data were incompatible with this approximation. The other
      special case required that the sum of the lambda i vary linearly with actin
      concentration and the other two combinations of lambda i vary with actin
      concentration in a quadratic fashion. The present data were in agreement with the
      second case. At 20 degrees C and in 60 mM KCl, 2 mM MgCl2, 30 mM 2-([-hydroxy-1,1
      bis(hydroxymethyl)ethyl]amino)ethanesulfonic acid, and pH 7.5, the biomolecular
      association rate constants for the interaction of actin with S1' and S1 were 8.58
      x 10(5) and 1.11 x 10(6) M-1 s-1, respectively.

PMID- 8274638
TI  - Calcium ion regulation of chirality of beating flagellum of reactivated sea
      urchin spermatozoa.
AB  - Near an interface, sea urchin spermatozoa swim almost in circles. The direction
      is usually clockwise at the lower surface of a coverslip and counterclockwise at
      the upper surface of a glass slide, when viewed from above. Examination of
      demembranated spermatozoa has shown that Ca2+ regulates the direction of the
      circular motion of spermatozoa reactivated with adenosine triphosphate (ATP).
      This finding suggests that Ca2+ changes the chirality of the three-dimensional
      bending waves of sperm flagella.

PMID- 8274639
TI  - Photochemical conversion of the O-intermediate to 9-cis-retinal-containing
      products in bacteriorhodopsin films.
AB  - The photochemical activity of the O-state was investigated in bacteriorhodopsin
      (BR) films containing wildtype BR at pH 6.5 in the presence of glycerol. The
      formation of a photoproduct of O with an absorption maximum at 490 nm and 9-cis
      retinal configuration was found. This 490-nm product was named P and shows a slow
      thermal reaction into a compound with a maximal absorption at 380 nm which was
      named Q and contains free 9-cis-retinal in the proteins binding site. The
      photoproducts of O, i.e., P and Q, are very similar, or even identical, to those
      previously observed in blue membranes. Common to the O-state and blue membrane
      forms of bacteriorhodopsin is a protonated aspartic acid 85, and we suggest that
      it is the reduced negative charge around the Schiff base which is responsible for
      the 9-cis photoisomerization. The release of a proton from aspartic acid 85 is
      linked to the conversion of the O-state back to the initial state of BR.
      Therefore the conditions of low proton mobility in BR films containing glycerol
      favor the accumulation of the O-state. For optical and holographic applications
      such BR films are very attractive. It is possible to create photoproducts with
      red light which are thermally stable at room temperature and that can be
      photochemically erased. Dependent on the light composition both properties can be
      realized in the same sample material. This feature may bridge the gap between
      information processing and short-term and long-term storage of information with
      BR.

PMID- 8274640
TI  - Simulation of NMR data from oriented membrane proteins: practical information for
      experimental design.
AB  - Several hundred solid state NMR dipolar couplings and chemical shift anisotropies
      were simulated for the polytopic membrane protein, bacteriorhodopsin, and for an
      idealized transmembrane peptide conforming to several different secondary
      structures (alpha- and 3(10)-helices and parallel and antiparallel beta-sheets),
      each at several tilt angles with respect to the bilayer normal. The use of
      macroscopically oriented samples was assumed. The results of these simulations
      suggest: (i) Because of the r-3 dependence of dipolar coupling, it is likely to
      prove difficult to successfully execute uniform isotopic enrichment strategies to
      generate large numbers of quantitatively interpretable structural measurements in
      oriented sample NMR studies of membrane proteins. (ii) There are a number of
      readily implementable specific isotopic labeling schemes which can yield data
      patterns sufficient to identify local secondary structure for transmembrane
      segments of idealized proteins which are tilted by < 10 degrees with respect to
      the bilayer normal. (iii) The measurement of dipolar coupling constants between
      13C-, 19F-, and/or 3H-labeled side chains of proximal residues may prove
      effective as routes to long range tertiary structural data constraints.

PMID- 8274641
TI  - Structural heterogeneity of the Fe(2+)-N epsilon (HisF8) bond in various
      hemoglobin and myoglobin derivatives probed by the Raman-active iron histidine
      stretching mode.
AB  - We have examined the Fe(2+)-N epsilon (HisF8) complex in hemoglobin A (HbA) by
      measuring the band profile of its Raman-active nu Fe-His stretching mode at pH
      6.4, 7.0, and 8.0 using the 441-nm line of a HeCd laser. A line shape analysis
      revealed that the band can be decomposed into five different sublines at omega 1
      = 195 cm-1, omega 2 = 203 cm-1, omega 3 = 212 cm-1, omega 4 = 218 cm-1, and omega
      5 = 226 cm-1. To identify these to the contributions from the different subunits
      we have reanalyzed the nu Fe-His band of the HbA hybrids alpha(Fe)2 beta(Co)2 and
      alpha(Co)2 beta(Fe)2 reported earlier by Rousseau and Friedman (D. Rousseau and
      J. M. Friedman. 1988. In Biological Application on Raman Spectroscopy. T. G.
      Spiro, editor, 133-216). Moreover we have reanalyzed other Raman bands from the
      literature, namely the nu Fe-His band of the isolated hemoglobin subunits alpha
      SH- and beta SH-HbA, various hemoglobin mutants (i.e., Hb(TyrC7 alpha-->Phe),
      Hb(TyrC7 alpha-->His), Hb M-Boston and Hb M-Iwate), N-ethylmaleimide-des(Arg141
      alpha) hemoglobin (NES-des(Arg141 alpha)HbA) and photolyzed carbonmonoxide
      hemoglobin (Hb*CO) measured 25 ps and 10 ns after photolysis. These molecules are
      known to exist in different quaternary states. All bands can be decomposed into a
      set of sublines exhibiting frequencies which are nearly identical to those found
      for deoxyhemoglobin A. Additional sublines were found to contribute to the nu Fe
      His band of NES-des(Arg141 alpha) HbA and the Hb*CO species. The peak frequencies
      of the bands are determined by the most intensive sublines. Moreover we have
      measured the nu Fe-His band of deoxyHbA at 10 K in an aqueous solution and in a
      80% glycerol/water mixture. Its subline composition at this temperature depends
      on the solvent and parallels that of more R-like hemoglobin derivatives. We have
      also measured the optical charge transfer band III of deoxyHbA at room
      temperature and found, that at least three subbands are required to fit its
      asymmetric band shape. This corroborates the findings on the nu Fe-His band in
      that it is indicative of a heterogeneity of the Fe(2+)-N epsilon(HisF8) bond.
      Finally we measured the nu Fe-His band of horse heart deoxyMb at different
      temperatures and decomposed it into three different sublines. In accordance with
      what was obtained for HbA their intensities rather than their frequencies are
      temperature-dependent. By comparison with VFe-His bands of some Mb mutants (i.e.,
      Mb(His E7.->Gly) and Mb(HisE7__*Met) we suggest that these sublines may be
      attributed to different conformations of the heme pocket. Our data show, that the
      V Fe-His band is governed by at least two different coordinates x and y
      determining its frequency and intensity, respectively. While the former can be
      assigned to the tilt angle theta between the Fe2+-NJ(HisF8) bond and the heme
      normal and/or to the displacement delta of the iron from the heme plane,
      variations in the intensity may be caused by changes of the azimuthal angle phi
      formed by the projection of the proximal imidazole and the N(l)-Fe2+-N(III) line
      of the heme. The sublines are therefore interpreted as resulting from different
      conformational substates of the Fe2+-N(HisFa) complex which differ in terms of x
      (theta and/or delta). Each of them may further be subdivided in sub-substates
      with respect to the coordinate y (theta). Quaternary and tertiary transitions of
      the protein alter the population of these substates thus giving rise to a
      redistribution of the VFe-HiS sublines which shifts the corresponding peak
      frequency to higher values.

PMID- 8274642
TI  - Rotational and translational water diffusion in the hemoglobin hydration shell:
      dielectric and proton nuclear relaxation measurements.
AB  - The dynamic properties of water in the hydration shell of hemoglobin have been
      studied by means of dielectric permittivity measurements and nuclear magnetic
      resonance spectroscopy. The temperature behavior of the complex permittivity of
      hemoglobin solutions has been measured at 3.02, 3.98, 8.59, and 10.80 GHz. At a
      temperature of 298 K the average rotational correlation time tau of water within
      a hydration shell of 0.5-nm thickness is determined from the activation
      parameters to be 68 +/- 10 ps, which is 8-fold the corresponding value of bulk
      water. Solvent proton magnetic relaxation induced by electron-nuclear dipole
      interaction between hemoglobin bound nitroxide spin labels and water protons is
      used to determine the translational diffusion coefficient D(T) of the hydration
      water. The temperature dependent relaxation behavior for Lamor frequencies
      between 3 and 90 MHz yields an average value D(298K) = (5 +/- 2) x 10(-10)m2 s-1,
      which is about one-fifth of the corresponding value of bulk water. The decrease
      of the water mobility in the hydration shell compared to the bulk is mainly due
      to an enhanced activation enthalpy.

PMID- 8274643
TI  - Ligand binding to heme proteins: II. Transitions in the heme pocket of myoglobin.
AB  - Phenomena occurring in the heme pocket after photolysis of carbonmonoxymyoglobin
      (MbCO) below about 100 K are investigated using temperature-derivative
      spectroscopy of the infrared absorption bands of CO. MbCO exists in three
      conformations (A substrates) that are distinguished by the stretch bands of the
      bound CO. We establish connections among the A substates and the substates of the
      photoproduct (B substates) using Fourier-transform infrared spectroscopy together
      with kinetic experiments on MbCO solution samples at different pH and on
      orthorhombic crystals. There is no one-to-one mapping between the A and B
      substates; in some cases, more than one B substate corresponds to a particular A
      substate. Rebinding is not simply a reversal of dissociation; transitions between
      B substates occur before rebinding. We measure the nonequilibrium populations of
      the B substates after photolysis below 25 K and determine the kinetics of B
      substate transitions leading to equilibrium. Transitions between B substates
      occur even at 4 K, whereas those between A substates have only been observed
      above about 160 K. The transitions between the B substates are nonexponential in
      time, providing evidence for a distribution of substates. The temperature
      dependence of the B substate transitions implies that they occur mainly by
      quantum-mechanical tunneling below 10 K. Taken together, the observations suggest
      that the transitions between the B substates within the same A substate reflect
      motions of the CO in the heme pocket and not conformational changes. Geminate
      rebinding of CO to Mb, monitored in the Soret band, depends on pH. Observation of
      geminate rebinding to the A substates in the infrared indicates that the pH
      dependence results from a population shift among the substates and not from a
      change of the rebinding to an individual A substate.

PMID- 8274644
TI  - Nonlinear kinetics of ferritin adsorption.
AB  - The adsorption of ferritin at a methylized quartz surface was measured with off
      null ellipsometry and transmission electron microscopy. An initial lag-phase was
      seen, followed by an accelerating adsorption leading to mass transport limitation
      of the reaction. The rate of adsorption then decreased at a surface concentration
      far below monolayer coverage, and a continuously decreasing rate of binding was
      seen. The slope of the binding rate was linear with the logarithm of time
      (fractal kinetics). The adsorbed ferritin molecules were distributed in clusters
      as seen by transmission electron microscopy. Clusters grown during the mass
      transport limited adsorption had crystalline structure at short range and low
      fractal dimensions (df = 0.89) over long range. Clusters grown during adsorption
      with fractal kinetics showed random structure at short range and a high fractal
      dimension df = 1.86 over all ranges. These findings indicate some new important
      mechanisms responsible for the complex kinetics of macromolecular reactions at
      solid-liquid interfaces. The results are discussed in relation to recently
      developed theories of self-organized criticality.

PMID- 8274645
TI  - Structural and dynamic characterization of the aromatic amino acids of the human
      immunodeficiency virus type I nucleocapsid protein zinc fingers and their
      involvement in heterologous tRNA(Phe) binding: a steady-state and time-resolved
      fluorescence study.
AB  - The steady-state and time-resolved fluorescence properties of two zinc-saturated
      18-residue synthetic peptides with the amino acid sequence of the NH2-terminal
      (NCp7 13-30 F16W, where the naturally occurring Phe was replaced by a Trp
      residue) and the COOH-terminal (NCp7 34-51) zinc finger domains of human
      immunodeficiency virus type I nucleocapsid protein were investigated.
      Fluorescence intensity decay of both Trp 16 and Trp 37 residues suggested the
      existence of two fully solvent-exposed ground-state classes governed by a C = 2.2
      equilibrium constant. The lifetimes of Trp 16 classes differed from those of Trp
      37 essentially because of differences in nonradiative rate constants. Arrhenius
      plots of the temperature-dependent nonradiative rate constants suggested that the
      fluorescence quenchers involved in both classes and in both peptides were
      different and the collisional rate of these quenchers with the indole ring was
      very low, probably because of the highly constrained peptide chain conformation.
      The nature of the ground-state classes was discussed in relation to 1H nuclear
      magnetic resonance data. Using Trp fluorescence to monitor the interaction of
      both peptides with tRNA(Phe) we found that a stacking between the indole ring of
      both Trp residues and the bases of tRNA(Phe) occurred. This stacking constituted
      the main driving force of the interaction and modified the tRNA(Phe)
      conformation. Moreover, the binding of both fingers to tRNA(Phe) was
      noncooperative with similar site size (3 nucleotide residues/peptide), but the
      affinity of the NH2-terminal finger domain (K = 1.3 (+/- 0.2) 10(5) M-1) in low
      ionic strength buffer was one order of magnitude larger than the COOH-terminal
      one due to additional electrostatic interactions involving Lys 14 and/or Arg 29
      residues.

PMID- 8274646
TI  - Topological mechanisms involved in the formation of clathrin-coated vesicles.
AB  - By examining the basic characteristics of clathrin lattices, we discover that
      simple topological rules impose strict constraints on clathrin lattice
      transformations. These constraints require that internal bond rearrangements take
      place in conjunction with the addition or removal of pairs of clathrin
      triskelions within the interior of existing clathrin lattice patches. Similar
      constraints also are relevant to coated-vesicle shape changes and their budding
      off from pit lattices. Via specific illustrations, successive vesicles with
      hexagonal-barrel and other coats are shown to grow out from the interior of a
      initially flat clathrin-coated pit so long as free triskelions are available from
      cytoplasm. Concomitantly, we present mathematical derivations of several simple
      and useful topological equations. These equations govern the numbers of
      nonhexagonal clathrin lattice facets and their variations during internal shape
      transformations and justify the proposed mechanisms of triskelion pair insertion
      and removal.

PMID- 8274647
TI  - Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons.
AB  - The oscillatory properties of single thalamocortical neurons were investigated by
      using a Hodgkin-Huxley-like model that included Ca2+ diffusion, the low-threshold
      Ca2+ current (lT) and the hyperpolarization-activated inward current (lh). lh was
      modeled by double activation kinetics regulated by intracellular Ca2+. The model
      exhibited waxing and waning oscillations consisting of 1-25-s bursts of slow
      oscillations (3.5-4 Hz) separated by long silent periods (4-20 s). During the
      oscillatory phase, the entry of Ca2+ progressively shifted the activation
      function of lh, terminating the oscillations. A similar type of waxing and waning
      oscillation was also observed, in the absence of Ca2+ regulation of lh, from the
      combination of lT, lh, and a slow K+ current. Singular approximation showed that
      for both models, the activation variables of lh controlled the dynamics of
      thalamocortical cells. Dynamical analysis of the system in a phase plane diagram
      showed that waxing and waning oscillations arose when lh entrained the system
      alternately between stationary and oscillating branches.

PMID- 8274648
TI  - Cooperative behavior of K+ channels in the tonoplast of Chara corallina.
AB  - Spontaneous cooperatively of K+ channels is studied in excised patches of Chara
      corallina tonoplasts. Bar histograms (dwell time versus number of open channels)
      are constructed from the time series of current by means of the higher-order
      Hinkley detector (R. Schultze and S. Draber. 1993. J. Membr. Biol. 132:41-52). A
      statistical test, based on these bar histograms, shows that the channels are not
      independent. Further analysis reveals that the channels are cooperatively
      changing their open probability, which leads to the idea of cooperative mode
      shifting.

PMID- 8274649
TI  - Thermodynamic entropy of two conformational transitions of single Na+ channel
      molecules.
AB  - Single cardiac Na+ channel currents were recorded with improved resolution
      (bandwidth up to 20 kHz) at two temperatures, 10 and 25 degrees C. The mean open
      time was determined at voltages between -50 and 0 mV by evaluation of the
      distribution of the event-related gaps in the center of the baseline noise. Fit
      of the voltage-dependent reciprocal mean open times at both temperatures allowed
      even for a single channel molecule to separate an entropic from an enthalpic part
      of activation energy for both deactivation and inactivation. Both entropies are
      positive and the entropy of deactivation exceeds that of inactivation by more
      than twice.

PMID- 8274650
TI  - Trans-unsaturated lipid dynamics: modulation of dielaidoylphosphatidylcholine
      acyl chain motion by ethanol.
AB  - Acyl chain dynamics of the trans-unsaturated lipid, dielaidoylphosphatidylcholine
      (DEPC), were studied by conventional and saturation transfer electron
      paramagnetic resonance spectroscopy of aqueous dispersions of DEPC spin labeled
      with lecithins having doxyl groups at positions 5, 10, and 14 on the sn-2 chain.
      The gel to liquid crystalline transition is concerted with simultaneous increases
      in rotational motion about the long axis of the acyl chain (libration) and in
      gauche-trans conformational interconversions (wobble). Relative to saturated
      lecithins at similar reduced temperatures the double bond (a) slowed libration by
      an order of magnitude in both phases, while wobble motions were several times
      slower, and (b)-produced a pronounced stiffness of the acyl chain near the double
      bond. Ethanol (0-1.6 M), in addition to its well-known colligative effect on the
      phase transition, was found to decrease the bilayer order in a concentration
      dependent manner. This effect was smaller in the gel than in the liquid
      crystalline phase, most pronounced next to the double bond, and weakest deep in
      the bilayer. Ethanol affected slow motions little in the gel phase but wobble and
      libration correlation times were markedly decreased in the liquid crystalline
      phase.

PMID- 8274651
TI  - Ca2+ transients in cardiac myocytes measured with high and low affinity Ca2+
      indicators.
AB  - Intracellular calcium ion ([Ca2+]i) transients were measured in voltage-clamped
      rat cardiac myocytes with fura-2 or furaptra to quantitate rapid changes in
      [Ca2+]i. Patch electrode solutions contained the K+ salt of fura-2 (50 microM) or
      furaptra (300 microM). With identical experimental conditions, peak amplitude of
      stimulated [Ca2+]i transients in furaptra-loaded myocytes was 4- to 6-fold
      greater than that in fura-2-loaded cells. To determine the reason for this
      discrepancy, intracellular fura-2 Ca2+ buffering, kinetics of Ca2+ binding, and
      optical properties were examined. Decreasing cellular fura-2 concentration by
      lowering electrode fura-2 concentration 5-fold, decreased the difference between
      the amplitudes of [Ca2+]i transients in fura-2 and furaptra-loaded myocytes by
      twofold. Thus, fura-2 buffers [Ca2+]i under these conditions; however, Ca2+
      buffering is not the only factor that explains the different amplitudes of the
      [Ca2+]i transients measured with these indicators. From the temporal comparison
      of the [Ca2+]i transients measured with fura-2 and furaptra, the apparent reverse
      rate constant for Ca2+ binding of fura-2 was at least 65s-1, much faster than
      previously reported in skeletal muscle fibers. These binding kinetics do not
      explain the difference in the size of the [Ca2+]i transients reported by fura-2
      and furaptra. Parameters for fura-2 calibration, Rmin, Rmax, and beta, were
      obtained in salt solutions (in vitro) and in myocytes exposed to the Ca2+
      ionophore, 4-Br A23187, in EGTA-buffered solutions (in situ). Calibration of fura
      2 fluorescence signals with these in situ parameters yielded [Ca2+]i transients
      whose peak amplitude was 50-100% larger than those calculated with in vitro
      parameters. Thus, in vitro calibration of fura-2 fluorescence significantly
      underestimates the amplitude of the [Ca2+]i transient. These data suggest that
      the difference in amplitude of [Ca2+]i transients in fura-2 and furaptra-loaded
      myocytes is due, in part, to Ca2+ buffering by fura-2 and use of in vitro
      calibration parameters.

PMID- 8274652
TI  - Acid-induced dissociation of alpha A- and alpha B-crystallin homopolymers.
AB  - Homopolymers were constructed from the alpha A and alpha B polypeptides isolated
      from the lens protein alpha-crystallin. As the pH is lowered from 7.0 to 3.4,
      these homopolymers dissociate to smaller species with molecular masses ranging
      from 80 to 250 kDa for the alpha A and around 140 kDa for the alpha B
      dissociation products. The pKa for this dissociation was 3.8 +/- 0.2 for alpha A
      and 4.1 +/- 0.1 for alpha B homopolymers. Further decreases in pH, to 2.5,
      resulted in the presence of only denatured alpha B polypeptides, whereas the
      alpha A dissociation products remained intact. Fractionation of the acid
      dissociation products from the alpha A homopolymer at pH 2.5 yielded stable
      species with molecular masses of 220 +/- 30, 160 +/- 20, and 90 +/- 10 kDa. The
      majority of the population at acid pH consisted of the 160 kDa species.
      Conformational analysis of these species revealed that most of the secondary
      structure of the original alpha A homopolymer was retained but that the tertiary
      structure was perturbed. Fluorescence quenching and energy transfer measurements
      suggested that the molecule had undergone acid expansion, with the greatest
      perturbation observed in the smallest particles. The results from this work
      suggest that alpha A homopolymers are heterogeneous populations of aggregates of
      a "monomeric" molecule with a molecular mass of 160 kDa. This "monomeric"
      molecule may be formed from the association of two tetrameric units.

PMID- 8274653
TI  - Multiple hydration layers in cubic insulin crystals.
AB  - Cubic insulin crystals contain approximately 30-A-diameter channels filled with
      aqueous solvent, providing a useful system in which to analyze hydration
      structure at a variety of distances from protein surfaces. Beginning with an
      atomic model for the protein and ordered water molecules, the density
      distribution in the solvent volume of the phasing model was iteratively refined
      to improve the fit of calculated structure factors with x-ray diffraction data.
      The free R value, which compares calculated structure factors with a subset of
      observed structure factors deliberately omitted from the refinement, was used to
      provide an objective confirmation of the effectiveness of the refinement
      procedure. Electron density maps of the solvent, computed using the solvent
      refined phases and complete low-resolution diffraction data, reveal multiple
      hydration layers around the protein.

PMID- 8274654
TI  - A photoacoustic calorimetry study of horse carboxymyoglobin on the 10-nanosecond
      time scale.
AB  - The development of a photoacoustic calorimeter with a time resolution of 10 ns is
      presented, and the dynamics of the enthalpy and volume changes found in the
      photodissociation of CO from horse carboxymyoglobin are examined. With this
      enhanced time resolution a new transient species, the lifetime of which is 29 ns
      at 20 degrees C, is observed in the ligand dissociation process.

PMID- 8274655
TI  - Using large organic cations to probe the nature of ryanodine modification in the
      sheep cardiac sarcoplasmic reticulum calcium release channel.
AB  - We have reported that the large impermeant organic cations tetrabutyl ammonium
      (TBA+), tetrapentyl ammonium, and the charged local anesthetic QX314 produce
      unique reduced conductance states in the purified sheep cardiac sarcoplasmic
      reticulum Ca2+ release channel when present at the cytoplasmic face of the
      channel. We have interpreted this as a form of partial occlusion by the blocking
      cation in wide vestibules of the conduction pathway. Following modification with
      ryanodine, which causes the channel to enter a reduced conductance state with
      long open dwell time, these cations block the receptor channel to a level that is
      indistinguishable from the closed state. The voltage dependence of TBA+'s
      interaction with the Ca2+ release channel is the same before and after ryanodine
      modification. The concentration dependence is different, in that the ryanodine
      modified channel has one-third the affinity for TBA+, which is accounted for
      predominantly by changes in the TBA+ on rate. The data are compatible with a
      structural change in the vestibule of the conduction pathway consequent upon
      ryanodine binding that reduces the capture radius for blocking ion entry.

PMID- 8274656
TI  - Study of mechanisms of electric field-induced DNA transfection. V. Effects of DNA
      topology on surface binding, cell uptake, expression, and integration into host
      chromosomes of DNA in the mammalian cell.
AB  - Neumann and coworkers (Neumann, E., M. Schaefer-Ridder, Y. Wang, and P. H.
      Hofschneider. 1982. EMBO J. 1:841-845) have shown that the efficiency of pulsed
      electric field (PEF)-induced DNA transfection of mouse L-cells by the thymidine
      kinase gene is several times higher for the linear DNA than for the closed
      circular DNA. Transfection of Escherichia coli bacteria by several plasmids
      indicates that the transfection efficiency was much higher for the closed
      circular/supercoiled (sc-) and circular/relaxed (cr-) DNA than for the linearized
      (In-) DNA (Xie, T. D., L. Sun, H. G. Zhao, J. A. Fuchs, and T. Y. Tsong. 1992.
      Biophys. J. 63:1026-1031). To resolve these conflicting observations, we have
      systematically examined electrotransfection of NIH3T3 mouse fibroblast by the
      plasmids, pRSVcat, pRSVneo, and pRSVgpt. Mg(2+)-facilitated surface binding of
      DNA before, and DNA uptake by 3T3 cells after treatment with PEF, were monitored
      by 3H-labeled plasmids. Transfection efficiency was evaluated by both the
      transient expression of chloramphenicol acetyltransferase (cat) activity 2-3 days
      after, and the permanent expression of neomycin phosphotransferase (neo) and
      xanthine-guanine phosphoribosyltransferase (gpt) genes in the transformants 2
      weeks after the PEF treatment. Our results indicate that cell surface binding and
      PEF-induced cell uptake of DNA did not depend on the topology of DNA. However,
      both the transient and the permanent expression of the plasmids were three to
      five times more efficient for the cr-DNA and the sc-DNA than for the in-DNA.
      These results indicate that electrotransfection of cells involves several steps:
      the cation-dependent binding of DNA to the cell surface, the electric field
      driven DNA entry into the cells, the transient expression of DNA, and the
      integration of DNA into the host chromosomes. For understanding mechanisms of
      electrotransfection, only the DNA binding to the cell surface and the electric
      field assisted membrane-crossing of DNA are relevant. Both the expression of the
      loaded DNA and the DNA integration into the host chromosomes depend more on the
      properties of the cell and its interactions with a foreign gene. Since these
      properties and interactions will be similar irrespective of the method chosen to
      facilitate DNA transfer, they are not relevant for the study of mechanisms of
      electrotransfection. Our results also support the idea that the PEF-induced
      cellular uptake of DNA is mainly by the electrophoresis of the surface bound DNA
      across the plasma membrane.

PMID- 8274657
TI  - Chromatin changes in cell transformation: progressive unfolding of the higher
      order structure during the evolution of rat hepatocyte nodules. A differential
      scanning calorimetry study.
AB  - Using differential scanning calorimetry and complementary ultrastructural
      observations, we have characterized the status of chromatin during the
      transformation of rat hepatocytes in the resistant hepatocyte model of Solt and
      Farber (1976. Nature (Lond.). 263:701-703). Differential scanning calorimetry
      affords a measure of the degree of condensation of chromatin in situ and has
      therefore been used in this work for the purpose of establishing the nature of
      the structural changes associated with the emergence of successive cellular
      populations. Since the resistant hepatocyte model generates a series of
      synchronous phenotypic changes, it was possible to determine unambiguously the
      content of heterochromatin at each step of the process. The higher-order
      structure undergoes a partial relaxation in early developing nodules, isolated 16
      weeks after initiation; the thermal transition at 90 degrees C, which is
      characteristic of noninteracting core particles, increases with respect to
      control hepatocytes. Dramatic changes occur in persistent (46-week) nodules. The
      90 degrees C endotherm dominates the thermogram, while the transition at 107
      degrees C, corresponding to the denaturation of the core particle packaged within
      the heterochromatic domains, disappears. The complete loss of the higher-order
      structure at this stage of transformation has been further verified by
      ultrastructural observations on thin nuclear sections. Ten-nm filaments, having a
      beaded appearance, are scattered throughout the nucleoplasm and clearly result
      from the decondensation of 30-nm-thick fibers. This catastrophic relaxation
      process cannot be related to an effective increase in gene activity. Rather, our
      observations suggest that during transformation chromatin is in a state of high
      transcriptional competence associated with the alert of general cellular
      programs. This view is consistent with the finding that in persistent nodules the
      DNA is extensively hypomethylated with respect to normal liver.

PMID- 8274658
TI  - Composite cylinder models of DNA: application to the electrostatics of the B-Z
      transition.
AB  - We develop and test a Poisson-Boltzmann model of the electrostatics of the B-Z
      transition of DNA. Starting from the detailed geometries of the two forms, we
      compute at each radius the fractions of DNA matter, of volume forbidden (for
      nonpoint-like ions), and of volume accessible to the center of ions. These radial
      distributions are incorporated in a composite cylinder model; availability to
      ions (porosity) and the dielectric constant at each radial distance are then
      obtained. The phosphate charge is distributed with cylindrical symmetry on two
      layers at the appropriate radial distances. The porous sheath, between the axis
      and the charge distribution, provides much more room for ions in B-DNA than in Z
      DNA. By using previously developed methods, the Poisson-Boltzmann problem of such
      cylinders is easily solved. The computational load is small, so that results can
      be obtained for a large set of salt concentrations and for a number of ionic
      radii. The variation of the electrostatic free energy difference with salt
      concentration compares favorably with the experimental value (it is half as
      large). There is also qualitative agreement with experiments on supercoiled DNA,
      including a maximum of the free energy difference at submolar salt
      concentrations. The results for this cylinder with porous sheath are in line with
      those of the earlier simple planar model and of a plain cylinder with sheath,
      which is also presented here. They are thus insensitive to details of the model.
      They support the proposition that the main electrostatic feature of the B-Z
      transition is the better immersion of the B-DNA phosphates into the solution.
      They also give confidence in the validity of the Poisson-Boltzmann approach,
      despite the large salt concentrations involved. Prior studies using an approach
      based on the potential of mean force are discussed.

PMID- 8274659
TI  - Two-dimensional crystallization of streptavidin by nonspecific binding to a
      surface film: study with a scanning electron microscope.
AB  - A two-dimensional (2D) crystal of streptavidin has been obtained by a nonspecific
      binding method. The protein molecules were bound and formed a dense packing on
      the film of poly(1-benzyl-L-histidine) spread at the surface of protein solution.
      The surface film was moderately heated to stimulate crystallization of bound
      streptavidin. A potential of this method for obtaining 2D crystals of soluble
      proteins is demonstrated. The present 2D crystal structure of streptavidin
      resembles that previously obtained by specific binding to biotinylated lipid. We
      show in addition that the 2D array of protein with usual size approximately 50 A
      can be imaged using a high resolution scanning electron microscope (HR-SEM) and
      subject to structural analysis at low resolution. Various limitations in HR-SEM
      degrade considerably the image quality. However, the usability of a bulk plate as
      specimen support would make HR-SEM a convenient tool, when such a substrate must
      be considered in application of protein arrays, and if an intrinsic low
      resolution is acceptable.

PMID- 8274660
TI  - Time-resolved absorption and magnetic circular dichroism spectroscopy of
      cytochrome c3 from Desulfovibrio.
AB  - The UV-visible absorption and magnetic circular dichroism (MCD) spectra of the
      ferric, ferrous, CO-ligated forms and kinetic photolysis intermediates of the
      tetraheme electron-transfer protein cytochrome c3 (Cc3) are reported. Consistent
      with bis-histidinyl axial coordination of the hemes in this Class III c-type
      cytochrome, the Soret and visible region MCD spectra of ferric and ferrous Cc3
      are very similar to those of other bis-histidine axially coordinated hemeproteins
      such as cytochrome b5. The MCD spectra indicate low spin state for both the
      ferric (S = 1/2) and ferrous (S = 0) oxidation states. CO replaces histidine as
      the axial sixth ligand at each heme site, forming a low-spin complex with an MCD
      spectrum similar to that of myoglobin-CO. Photodissociation of Cc3-CO (observed
      photolysis yield = 30%) produces a transient five-coordinate, high-spin (S = 2)
      species with an MCD spectrum similar to deoxymyoglobin. The recombination
      kinetics of CO with heme Fe are complex and appear to involve at least five first
      order or pseudo first-order rate processes, corresponding to time constants of
      5.7 microseconds, 62 microseconds, 425 microseconds, 2.9 ms, and a time constant
      greater than 1 s. The observed rate constants were insensitive to variation of
      the actinic photon flux, suggesting noncooperative heme-CO rebinding. The growing
      in of an MCD signal characteristic of bis-histidine axial ligation within tens of
      microseconds after photodissociation shows that, although heme-CO binding is
      thermodynamically favored at 1 atm CO, binding of histidine to the sixth axial
      site competes kinetically with CO rebinding.

PMID- 8274661
TI  - A single-pool model for intracellular calcium oscillations and waves in the
      Xenopus laevis oocyte.
AB  - We construct a minimal model of cytosolic free Ca2+ oscillations based on Ca2+
      release via the inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ channel (IP3R)
      of a single intracellular Ca2+ pool. The model relies on experimental evidence
      that the cytosolic free calcium concentration ([Ca2+]c) modulates the IP3R in a
      biphasic manner, with Ca2+ release inhibited by low and high [Ca2+]c and
      facilitated by intermediate [Ca2+]c, and that channel inactivation occurs on a
      slower time scale than activation. The model produces [Ca2+]c oscillations at
      constant [IP3] and reproduces a number of crucial experiments. The two
      dimensional spatial model with IP3 dynamics, cytosolic diffusion of IP3 (Dp = 300
      microns 2 s-1), and cytosolic diffusion of Ca2+ (Dc = 20 microns 2 s-1) produces
      circular, planar, and spiral waves of Ca2+ with speeds of 7-15 microns.s-1, which
      annihilate upon collision. Increasing extracellular [Ca2+] influx increases wave
      speed and baseline [Ca2+]c. A [Ca2+]c-dependent Ca2+ diffusion coefficient does
      not alter the qualitative behavior of the model. An important model prediction is
      that channel inactivation must occur on a slower time scale than activation in
      order for waves to propagate. The model serves to capture the essential
      macroscopic mechanisms that are involved in the production of intracellular Ca2+
      oscillations and traveling waves in the Xenopus laevis oocyte.

PMID- 8274662
TI  - Substitution of a hydrophobic residue alters the conformational stability of
      Shaker K+ channels during gating and assembly.
AB  - A leucine residue at position 370 (L370) in 29-4 Shaker K+ channels resides
      within two overlapping sequence motifs conserved among most voltage-gated
      channels: the S4 segment and a leucine heptad repeat. Here we investigate the
      effects observed upon substitution of L370 with many other uncharged amino acid
      residues. We find that smaller or more hydrophilic residues produce greater
      alterations in both activation and inactivation gating than does substitution
      with other large hydrophobic residues. In addition, subunits containing less
      conservative substitutions at position 370 are restricted in their assembly with
      wild-type subunits and are unlikely to form homomultimeric channel complexes.
      Consistent with the idea that L370 influences the tertiary structure of these
      channels, the results indicate that L370 undergoes specific hydrophobic
      interactions during the conformational transitions of gating; similar
      interactions may take place during the folding, insertion, or assembly of Shaker
      K+ channel subunits.

PMID- 8274663
TI  - Determination of Ki67 growth fraction and oestrogen receptors in screen-detected
      breast cancer using cytological preparations.
AB  - Oestrogen receptor (ER) status of 77 cases of screen-detected breast cancer has
      been determined using cytological preparations. In 48% ER status was positive,
      which was the same proportion as that formed in a control group of age-matched
      patients with symptomatic breast carcinoma. Since the screen-detected group
      contained more low grade tumours, the percentage of ER-positive cases would be
      expected to be higher. The reasons for the discrepancy are discussed. Ki67 score
      has been determined for 41 cases of screen-detected cancer. Ki67 score showed a
      positive correlation with histological tumour grade and a negative correlation
      with ER status. However, there was no correlation with tumour size or lymph node
      status. The Ki67 scores in the screen-detected cancers were essentially similar
      to those found in an age-matched symptomatic group, but the very low scores were
      only found in the screened group.

PMID- 8274664
TI  - Comparison of monoclonal antibodies AUA1 and BER EP4 with anti-CEA for detecting
      carcinoma cells in serous effusions and distinguishing them from mesothelial
      cells.
AB  - Commercially available monoclonal antibodies AUA1, BER EP4 and carcinoembryonic
      antigen (CEA) were applied to cell blocks from 95 serous effusions. AUA1 and BER
      EP4 were reactive with 89% of effusions known to contain carcinoma cells, and
      anti-CEA with 71%. They also reacted with cells in two effusions from patients
      with malignant disease which were regarded as negative on conventional
      cytological examination of Papanicolaou-stained smears. They were negative in all
      but one of the benign effusions. Using all three antibodies, 95% of effusions
      containing carcinoma cells were detected. Use of these antibodies could improve
      the cytological diagnosis of serous effusions.

PMID- 8274665
TI  - Patients with various types of human papillomavirus: covariation and diagnostic
      relevance of cytological findings in Papanicolaou smears.
AB  - Human papillomavirus (HPV) infection in the genital tract is associated with a
      number of cytological changes which are accepted as standard criteria for a
      cytological diagnosis. We evaluated the covariation and diagnostic accuracy of
      these criteria in 210 patients, i.e. 150 cases who were positive for HPV types 6,
      11, 16, 18, 31, 33 or 35, and 60 cases who were HPV-negative by simultaneous
      Southern blot analysis. This was done by re-examining cervical smears obtained at
      the same time, without knowing the results of the Southern blot analysis, for the
      presence of koilocytosis, dyskeratosis-parakeratosis, nuclear smudging,
      hyperchromasia, binucleation, multinucleation, karyorrhexis and macrocytosis. We
      found that all these cytological changes correlated with the presence of an HPV
      infection. However, analysis of variance showed that koilocytosis, dyskeratosis
      parakeratosis and karyorrhexis were of particular diagnostic value, while the
      other features provided little or no additional information. By omitting these
      features and making the diagnosis when two out of three of the key criteria, i.e.
      koilocytosis, dyskeratosis-parakeratosis and karyorrhexis were present, we
      diagnosed HPV infection with a specificity of 100% in 36% of the 150 cases, which
      were positive by Southern blot analysis. The various HPV types produced different
      morphological patterns which may reflect differences in action on the host cell.
      In the individual patient, however, such differences in cytology do not provide a
      sound basis for distinguishing between viral types.

PMID- 8274666
TI  - Cellular differences between true negative and false negative Papanicolaou
      smears.
AB  - A matched case-control study of 123 false negative Papanicolaou smears and 488
      true negative Papanicolaou smears was undertaken to determine the association
      between the types of cells present on the smear and the correctness of the
      cytology report. The false negative slides were significantly more likely to
      include endocervical columnar cells than the true negative slides (odds ratio
      1.90, 95% confidence interval (CI) 1.21-3.01). No statistically significant
      difference in metaplastic cell status was evident (odds ratio 1.48, 95% CI 0.95
      2.30). When considered together, metaplastic and/or columnar cells were
      significantly more likely to be present in false negative smears than in true
      negative smears (odds ratio 1.87, 95% CI 1.13-3.08). The implications of these
      findings for improving the accuracy of cervical cytology for the detection of
      precancerous lesions are discussed.

PMID- 8274667
TI  - An experience with ultrasonically guided liver aspirates from south India.
AB  - Fine needle aspiration (FNA) was performed on 102 hepatic lesions under
      ultrasound control. Eighty-eight lesions were solid and 14 were cystic. Ninety
      aspirates provided adequate material for cytodiagnosis. Aspirates from the solid
      lesions were assessed for the presence or absence of 20 cytological features. It
      was found that on a univariate statistical analysis, 11 of the features were
      significantly associated with hepatocellular carcinomas. Five of these 11 were
      considered diagnostic of the lesion on a step-wise multiple linear regression
      analysis. Two other features (not included among the 11) were found to be
      significantly associated with metastatic neoplasms. Cystic lesions were diagnosed
      as being either abscesses, hydatid cysts or congenital cysts. The physical
      appearance of the cyst fluid proved to be of diagnostic value in many cases.

PMID- 8274668
TI  - Comparison of fine needle sampling by capillary action and fine needle
      aspiration.
AB  - Fine needle aspiration (FNA) and non-suction fine needle sampling (FNS) were
      performed consecutively in 107 lesions from 100 patients. The quality of
      diagnostic material was assessed using a scoring system based on the cellularity
      and amount of blood in the smear. The total score in the FNS group was
      significantly higher (P < 0.05) than that of FNA technique. The FNS procedure is
      less traumatic and equally cost effective and can be safely undertaken in liver,
      orbital and thyroid lesions. In lymph nodes, especially in children, FNS gives an
      excellent cellular yield. However, this procedure can not be advocated in cystic,
      bony and fibrous lesions.

PMID- 8274669
TI  - Nodular fasciitis: a case with unusual clinical presentation initially diagnosed
      by aspiration cytology.

PMID- 8274670
TI  - Sacrococcygeal chordoma: fine needle aspiration cytological findings and
      differential diagnosis.

PMID- 8274671
TI  - Cytodiagnosis of rhabdomyosarcoma in serous effusions: cytological and
      immunocytochemical findings of two unusual clinical cases.

PMID- 8274672
TI  - [Cardiodynamics and cardiac pump function in hyperthermia].
AB  - Breaking of myocardial pumping function was shown in experiments in anesthesized
      dogs under hyperthermia. The end-systolic, end-diastolic and stroke volume was
      decreased under those conditions. The effectiveness of Frank-Starling mechanism
      was reduced in severe hyperthermia.

PMID- 8274673
TI  - [The parameters of grooming in the ontogeny of rats].
AB  - The grooming behaviour of rats includes different kinds of movements: scratching,
      licking, washing, shaking down, stinging out. All the parameters of these
      movements (their quantity, duration, and rhythm) were registered by graphic
      recording and may be objective indices of ontogenic development of grooming and
      the basis for the study of the mechanisms of grooming regulation.

PMID- 8274674
TI  - [The effect of the electrical stimulation of the superior colliculli on focal
      epileptic activity in the cerebral cortex ].
AB  - Acute experiments in rats showed that SC electrical stimulation (ES) (100 Hz, 5
      V, 0.25 ms) resulted in suppression of the epileptic activity in contralateral
      strychnine-induced (0.1%; 1.0%) focus and shortening of the focus existence time.
      After electrocoagulation of SC ES-zone the EpA in the focus was restored. ES of
      SC ipsilateral to strychnine-induced (0.1%) focus caused an increase in the spike
      frequencies but significant part of the antiepileptic system.

PMID- 8274675
TI  - [The effect of synthetic enkephalin analogs on the development of traumatic brain
      edema].
AB  - Experiments in rats showed i. p. injections of a dose of 0.1 mg/kg of highly mu
      selective agonist DAGO, relatively selective delta-receptor agonist DSLET and Tyr
      D-Ala-Gly-MePhe-Leu-Arg-NH-Et to attenuate markedly the development of cerebral
      edema 24 hours after brain injury. The same effect was found with administration
      of DSLET 4 days after trauma. Naloxone (1 mg/kg, i. p.) had no effect on this
      process, but completely blocked protective effect of peptides. These data
      demonstrate that both mu and delta opioid receptors are involved in the
      pathogenesis of traumatic cerebral edema.

PMID- 8274676
TI  - [A new natural model of elevated anxiety in rats].
AB  - The levels of anxiety were determined in male Wistar rats using a complex
      multiparameter method for evaluating anxiety-phobic states in rats based on
      ranged scale. The effects of psychotropic drugs differed in rats with innate high
      and low levels of anxiety. Anxiolytics sodium valproate (200 mg/kg), phenazepam
      (0.05 mg/kg) and diazepam (0.1 and 0.6 mg/kg) reduced anxiety in rats with innate
      high level of anxiety and prevented increase of anxiety induced by saline in rats
      with innate low level of anxiety. Pentylenetetrazol (10 mg/kg) and haloperidol at
      a large dose (0.5 mg/kg) increased anxiety in rats with either high or low innate
      levels of anxiety. However sodium lactate (600 mg/kg) increased anxiety only in
      rats with innate high level of anxiety. Haloperidol at a small dose (0.01 mg/kg)
      and melipramin (10 mg/kg) were uneffective in rats with innate high level of
      anxiety. Results believed the rats with innate high level of anxiety to be used
      as a new natural animal model of anxiety.

PMID- 8274677
TI  - [Individual differences in the reactions to acute stress related to behavioral
      type. Resistance (predisposition) to behavioral and sleep disorders].
AB  - Resistance (predisposition) to behavior and sleep disturbances after acute stress
      was studied in rats with different types of behavior in open field and forced
      swimming tests. The highest resistance to stress (the least alterations of
      behavior and sleep parameters) was found in rats with the active type of
      behavior, the least resistance to stress--in the middle group, and rats with the
      passive type of behavior held the intermediate position. The comparison of the
      present data with previously obtained results showed a positive correlation
      between the resistance to stress and the resistance to circulatory cerebral
      hypoxia induced by bilateral common carotid arteries occlusion. The biological
      significance of the association of resistance to stress and to cerebral hypoxia
      with the type of behavior is discussed.

PMID- 8274678
TI  - [The correction of postvagotomy disorders of the motor function in the small
      intestine by using antihypoxants and antioxidants].
AB  - Study of the electric activity of small intestine smooth muscle in vagotomized
      rats demonstrated diminution and disturbance of intestinal motility. These
      changes were most expressed within 30 days after vagotomy. Injection of
      antihypoxant sodium gamma-oxybutyrate and antioxidant dibunol to the vagotomized
      rats resulted in normalization of intestinal motility.

PMID- 8274679
TI  - [The dynamics of the development and regression of the phenomenon of adaptive
      structural stabilization correlates with a change in the hsp70 content in the
      myocardium].

PMID- 8274680
TI  - [A comparative analysis of the generalized activation of stress protein synthesis
      during adaptation to stress and hypoxia].

PMID- 8274681
TI  - [Changes in the efficacy of vasoconstrictor stimuli in acute and chronic
      hypotension in the microcirculatory bed of rat skeletal muscle].
AB  - Microvascular diameters in m. extensor hallucis proprius of rats were measured by
      the image split method. The baseline diameters and responses to the electrical
      stimulation (20 Hz, 10 s) of the sympathetic tract were obtained in arterioles i.
      d. 7.8-88 microns. Measurements were made under baseline pressure into the right
      femoral artery, 1 min after local blood pressure drop (LBPD) produced by
      inflation of the cuff around descending aorta and in the rats with the chronic (1
      2 months) regional hypotension (CRH) produced by implantation of a metal coil
      narrowing the aorta. Thirty five arterioles out of 45 showed reduction of
      responsiveness to sympathetic stimulation after LBPD (mean-19.1 +/- 2.1%), 6
      arterioles reacted by insignificant enhancing of the constrictor responses and
      the reactions of 3 vessels were more pronounced (mean-21.1 +/- 9.1%). The
      responsiveness to sympathetic stimulation of the skeletal muscle arterioles i. d.
      10-20 microns exposed to CRH did not differ from that in the sham-operated rats
      (11.6 +/- 1.3% vs 10.4 +/- 0.1%).

PMID- 8274682
TI  - [The intensification of nitric oxide synthesis in the aortic wall in experimental
      myocardial infarct].
AB  - The effect of experimental myocardial infarction on endothelium-dependent
      relaxation of isolated rat aorta and generation of nitric oxide in the aortic
      wall was studied. Three hours following myocardial infarction, the endothelium
      dependent relaxation induced with acetylcholine was increased to 61 +/- 2% as
      compared with 41 +/- 4% in control (r < 0.05). The nitric oxide generation (EPR
      assay) was 2.5 times increased in the aortic wall of animals subjected to
      myocardial infarction as compared with the control. The activated generation of
      nitric oxide may be provoked by the reduced minute volume of the heart and
      concomitant transient hypovolemia.

PMID- 8274683
TI  - [Intravascular measurements of the blood flow in rats].
AB  - The blood flow velocity in aorta was measured in rats with intravascular probes.
      Ultrasonic probes was fixed at the end of polyethylene tubing 0.6 mm in diameter.
      Miniature piezoelectric crystal worked on 33 MHz frequency. Simultaneously
      cardiac output were measured with cuff probes placed on ascending aorta.
      Correlative coefficient between them was 0.96 in static experiments. Dynamics of
      cardiac output process was caused by injection of vasoactive agents and asphyxia.
      The difference between intravascular probes and cuff probes blood flow parameters
      were 6-9%, strike volume 4-6%, cardiac output 5-7%. In ten cases intravascular
      probes was implanted in ascending aorta for hemodynamics study on conscious rats.

PMID- 8274684
TI  - [The role of the liver in regulating the blood iron biorhythms of rabbits with
      acute alcoholic intoxication].
AB  - Experiments with male California rabbits were carried out different intervals of
      acute alcohol intoxication induced by intragastric administration of 40% ethanol
      solution in a dose of 10 ml/kg to examine daily changes of concentration of iron,
      alpha-tocopherol and lipid peroxidation products in the blood plasma from vena
      portal and vena hepatis. Acute alcohol intoxication was demonstrated to be
      accompanied by inversion in temporal organization of lipid peroxidation products,
      sideremia and alpha-tocopherol levels in the blood of vena hepatis. The
      invariability of the circadian rhythms of iron, alpha-tocopherol and lipid
      peroxidation products levels in vena portal blood a considered to prove
      participation of the liver in regulation of iron metabolism temporal organization
      in California rabbits with acute alcohol intoxication.

PMID- 8274685
TI  - [The effect of the blood serum from patients subjected to intravenous laser
      therapy on the parameters of synaptic transmission].
AB  - The effect of serum of patients with myocardial ischemia after low-level laser
      therapy on parameters of synaptic conductance of rat hippocampal neurons was
      investigated. The serum from patients with an initially low level of neuronal
      activity obtained after determination of laser irradiation increased the
      amplitude and that from patients with high activity. Thus the process of
      normalization of these parameters was observed. Our results may help to optimize
      the course of medical treatment, and subsequently give an insight to
      understanding of the mechanism of therapeutic effect of laser irradiation.

PMID- 8274686
TI  - [The additive synthesis of a regulatory peptide in vivo: the administration of a
      vaccinal Francisella tularensis strain that produces beta-endorphin].
AB  - It has been shown, that vaccine strain of tularemia microbe, F.T.ISE., which
      produced recombinant beta-endorphin, when administered to CBA mice. It was shown
      to increase in the threshold level of pain sensitivity and is associated with
      peptides associated changes the stereotypic behavior. The observed correlated in
      time with the pattern of the dynamics of culture in the experimental animals and
      were associated with the level of recombinant beta-endorphin synthesis.

PMID- 8274687
TI  - [A spin-probe study of the structural change in human blood lipoproteins under
      the action of sodium hypochlorite].
AB  - The spin-probe technique was used to study structural changes in the surface
      proteolipid layer of human blood low-density lipoproteins (LDL) peroxidized to
      different degree by sodium hypochlorite (NaOCl). The paramagnetic analogs of
      stearic acid were employed as spin labels that contained nitroxide groups
      localized at different distances from the LDL surface. In addition, a positively
      charged spin label was used which was distributed at the lipid-water interface,
      in the area of polar phospholipid groups. NaOCl was shown to induce the lipid
      peroxidation of LDL. It diminished the mobility of polar "heads" as well as of
      acyl phospholipid chains up to 1.7 nm from the LDL particle surface and increased
      the polarity of lipid phase in this region. In the deeper layers (2.0-2.2 nm) the
      structural alterations in LDL were registered only at NaOCl concentration more
      than 1 mM.

PMID- 8274688
TI  - [The behavioral effects of beta-casomorphin-7 and its des-Tyr analogs].
AB  - The effects of intraperitoneal administration of the heptapeptide beta
      casomorphin-7 (beta-K-7) and its des-Tyr analogues (beta-K-6 and beta-K-4) on
      spontaneous locomotor activity were investigated in rats using "Opto-Varimax",
      "RODEO-2" and "open field" tests. At 20 mg/kg 5 minutes prior to the beginning of
      measurements beta-K-7 produced a significant decrease in linear locomotion and
      rearing. As for beta-K-6 and beta-K-4, their influence on locomotion of the
      experimental animals was less evident. In contrast to beta-K-7, its des-Tyr
      analogues (20 mg/kg) produced a marked decrease in nose-poking behavior. Beta-K-7
      in doses that had no effect on spontaneous behaviour (1 and 5 mg/kg) attenuated
      extreme behavioural displays under stress conditions. The experimental results
      suggest the advisability of further investigations of neurotropic properties of
      beta-K-7 and related peptides.

PMID- 8274689
TI  - [The effects of enkephalins on the water-salt metabolism of rats in ontogeny].
AB  - The experiments were carried out in white Wistar rats of three ages: 25-30 days
      (Group 1, n = 102), 45-50 days (group 2, n = 62), over 180 days (group 3, n =
      115). The water loading was given through a gastric tube in an amount of 5% of
      the body weight. A synthetic analogue of leu-enkephalin (SAE) was injected
      intraperitoneally in a dose of 100 mg/kg. The control animals received
      physiological saline. In the baby rats of group 1, administration of SAE slowed
      down the polyuric and ionouretic reactions in response to the water loading. In
      older rats of group 2 administration of SAE enhanced water elimination but with
      this the osmolarity of the blood plasma increased together with the content of
      potassium and sodium ions in it. In adult rats (group 3) injections of SAE
      produced a smooth diuretic reaction which retained constant ion levels in the
      blood plasma.

PMID- 8274690
TI  - [Changes in the neural activity of the blood serum from patients with ischemic
      heart disease].
AB  - The isolated neurons of snail (Lymnaea stagnalis) were as test object for the
      evaluation of the blood serum neuroactivity. The blood serum was tested before
      treatment and after six applications of intravenous laser therapy (ILT). All
      blood serum specimens produced depolarization of the cell membrane potential. The
      quantitative comparison of membrane toxicity of control and experimental blood
      serum specimens permitted to divide the patients into three groups. Blood serum
      (after six applications of ILT of patients from the first and second groups
      produced a lower membrane toxicity effect on neurons. In the groups the membrane
      toxicity effect decrease by 43% +/- 10.3 and 7.3 +/- 2.2% respectively. In third
      group the membrane toxicity effect increased by 21.5 +/- 4.5. All patients from
      the third group had myocardial infarction less than one year before being given a
      course on the treatment. The ILT was found to be able to decrease the activity of
      the blood serum components disrupting normal functioning of the ionic mechanisms
      of cell membranes.

PMID- 8274691
TI  - [The costimulating effect of chorionic gonadotropin on lymphokine-activated
      splenocytes. A new aspect of the immunomodulating action of the pregnancy
      hormone].
AB  - An immunodepressive effect of chorionic gonadotropin (CG) low (40IU) and high
      (200IU) doses on the processes of lymphocyte antigen-independent differentiation,
      realizing the primary immune response has been established in the short-term
      culture of mice splenic intact cells. Splenocyte activation by Con-A or human
      recombinant IL-2 does not show an expressive immunostimulating effect on the
      processes of plaque forming cells (PFC) formation. While the immunomodulating
      effect of CG on the background of these activators changes. In the presence of
      Con-A or IL-2, hormone in the dose of 40 IU can't effectively suppress the PFC
      formation processes. On the background of IL-2, CG-200IU shows an expressed
      opposite effect, increasing the splenocyte ability to form PFC twice as much. It
      is suggested, that CG appears to be a cofactor, intensifying the processes of
      immunocompetent cell proliferation and differentiation, connected with this
      lymphokine. A new aspect of the CG immunomodulating effect during pregnancy is
      being discussed now.

PMID- 8274692
TI  - [The effect of pro-oxidants on insulin secretion by the isolated rat pancreas].
AB  - The effect of pro-oxidants (tert-butyl peroxide and FeSO4) on rats perfusing
      isolated pancreas insulin secretion was studied. Pro-oxidants (10(-4) M)
      preperfusion during 20 minutes did not change significantly the basal insulin
      secretion and decreased glucose-stimulated secretion of the one. The content of
      pancreas TBA-active products increased twice after pro-oxidants effect and ratio
      of reduced and oxidized glutathiones liberation rates decreased from 2 to 0.5.
      The disturbance of hormone secretion as a result of decrease of Langerhans islets
      B-cells reduced glutathione pool is suppose to be one of the mechanisms of
      hypoinsulinemia development at host's states characterizing with lipids
      peroxidation activation.

PMID- 8274693
TI  - [The effect of using enalapril in experimental chronic kidney failure in
      spontaneously hypertensive rats].

PMID- 8274694
TI  - [The effect of nonsteroidal anti-inflammatory agents on erythrocyte osmotic
      resistance].
AB  - Effects of voltaren, surgam and isamben on erythrocyte membrane were studied.
      Voltaren and suggam, in dmM concentrations were to decrease, but in mM
      concentrations to increased hypotonic erythrocyte lysis. The role of erythrocyte
      membrane fluid is discussed with regard to this effect of the drugs, since
      voltaren or surgam, erythrocyte lysis even in isotonic medium at mM
      concentrations. In contrast to voltaren and surgam samben as had no effect on
      erythrocyte lysis in hypotonic or isotonic medium. In this connection, the
      relationship between membrane lytic effect and ulcerogenic potency of non
      steroidal anti-inflammatory drugs is discussed.

PMID- 8274695
TI  - [A pharmacological analysis of pentagastrin-modulated behavior evoked by
      stimulation of the ventromedial hypothalamus].
AB  - The purpose of the present investigations was to examine the neurochemical
      mechanisms of modulatory effect of pentagastrin (PG) on escape reaction elicited
      by the threshold electrical stimulation of the ventromedial hypothalamus (VMH) in
      rabbits. PG administration (35 mcg/kg intraventricularly) was found to transform
      escape into feeding. This phenomenon was shown to begin at 20 min and to last to
      150 min after PG injection. The animals were treated with various antagonists to
      some classic neurotransmitters of the central nervous system. Kalipsol (0.25, 0.5
      mg/kg intravenously) and ketanserin (0.1 mg/kg intravenously) were found to
      restore feeding into escape. GABA-ergic antagonist baclofen (0.25, 0.5 mg/kg) was
      demonstrated to shorten to about 30 min the time of feeding after PG
      administration. Both inderal-beta-adreno-blocker (0.25, 0.5, 1.0 mg/kg) and M
      choline antagonist atropine (0.25, 0.5 mg/kg) were found to be ineffective in
      escape restoration in response to VMH stimulation. The experimental results
      suggest the important role of N-cholinergic and serotoninergic brain structures
      in PG transformation of escape elicited from the VMH into feeding.

PMID- 8274696
TI  - [The mechanisms of the immunotropic effects of organophosphorus compounds].
AB  - The effects of acute poisoning with anticholinesterase insecticide
      dimethyldichlorvinylphosphate (DDVP) in doses 0.25; 0.5 and 1.0 LD 50,
      immobilisation stress (6-hour), hydrocortisone (100 mg/kg) and acetylcholine--A
      (5 mg/kg) on the basic immune responses were investigated in experiments on CBA
      mice. It was shown that increased migration of founder hemopoietic cells from the
      bone marrow was caused by the effect of A and that of T-cells from the thymus was
      induced by the actions of corticosterone (CS) and A. Suppressions of delayed-type
      hypersensitivity reaction, natural and antibody-dependent cellular cytotoxicity
      humoral immune response were directly associated with concentration of CS in the
      blood and inhibition of alpha-naphthylbutyratesterase in spleen cells. The
      function of nonspecific and specific mechanisms in the formation of
      immunodeficiency after intoxication with organophosphates chemicals was found to
      differ in immune resections under study.

PMID- 8274697
TI  - [The effect of interleukin-2 on rosette formation and its dependence on the
      serotonin level].
AB  - The analogy of the immunomodulating effects of the mediators of functionally
      coupled immune and serotoninergic systems was demonstrated in CBA mice immunized
      with sheep erythrocytes. Both agents in low doses stimulated and in high doses
      suppressed the response of the host to the antigen. Combined use of IL-2 and
      serotonin in optimal doses of similar action was shown to revert the effect into
      the opposite one. These data attest to the relationship of serotonin and IL-2 in
      the process of immunomodulation and to the importance of the balance of the
      substances in the environment at the moment of exposure to the antigenic
      information.

PMID- 8274698
TI  - [The activation of the proliferation of human corneal endothelium in malignant
      tumors of various sites and diabetes mellitus].
AB  - The morphological investigation of corneal endothelium was carried out in 205
      human eyes of patients with malignant tumors of different localization including
      the eye, and also with diabetes mellitus. The investigation was performed in flat
      specimens by electron microscopy. In all types of pathology mitotic figures were
      found in endothelial population, most frequently in cases of diabetes of moderate
      and severe degree. Simultaneously the endothelial cell density increased
      significantly comprising in case of choroidal melanoma 2416 cell/mm2, in cancer
      of different localization 2916 cell/mm2; in the control group in 40-60-year-old
      patients 2160 cell/mm2; in diabetes mellitus of moderate and severe degree 2770
      cell/mm2, in the control group in 60-80-year-old patients 1975 cell/mm.
      Simultaneously the endothelial cell area decreased significantly, the number of
      small unchanged cells of mitosis product increased and that of large cells
      diminished. Therefore, it growth factors in the host are more active, mitotic
      division of corneal endothelial cells will become more active as well.

PMID- 8274699
TI  - [A difference in the growth-controlling action of Syrian hamster fibroblasts from
      early and late embryogenesis on tumor cells with different degrees of
      malignancy].
AB  - The difference in the effect of embryo fibroblasts from early (EHEF) and late
      (LHEF) embryos on the proliferative activity (PA) of transformed and tumour cells
      of different degree of malignancy was demonstrated in culture. The dense
      monolayer of EHEF cells exerted stronger growth-inhibitory influence on the PA of
      all tested strains of the transformed and tumour cells as compared to the LHEF
      cells.

PMID- 8274700
TI  - [The subfractional composition of the blood plasma in benign tumors and cancer of
      the breast based on the data from laser correlational spectroscopy].
AB  - LCS was performed in 35 patients with mammary cancer, 59 patients with benign
      breast tumours and 35 healthy people. 39 samples were taken from inhabitants of
      Odessa, 89 from St.-Petersburg. Differences were discovered between blood plasma
      spectra of Odessa and St.-Petersburg residents. Spectra of blood plasma in
      patients with mammary tumours differed from those of healthy people. LCS may be
      used for screening, for forming the groups of risk and for diagnosis of mammary
      gland tumours.

PMID- 8274701
TI  - [The dynamic hematological indices in alcoholic intoxication in relation to the
      ecological situation].
AB  - Comparative investigations of conventional male rat red blood with modelling of
      chronic alcohol-toxic influence of different types were carried out. Even a short
      alcohol intoxication developing against the background of ecologically
      unfavourable factors of the environment was shown to cause rapid development of
      decompensation of the blood system protective mechanisms. In these cases
      hematologic picture resembled that after long and hard alcohol abuse.

PMID- 8274702
TI  - [Chronobiological patterns in the course of amphibian metamorphosis].
AB  - Metamorphic rates in Rana temporaria larvae treated with thyroxine and prolactin
      were observed in different phases of the light-dark cycle. Different hormonal
      effects on tadpole development were demonstrated depending on the light-dark
      phases. Thyroxine always accelerated the development. Thyroxine employed at L-D
      and D-L phases was more effective than in T and D phases. Prolactin retarded
      metamorphosis in D phase and accelerated in L-D phase. This work demonstrated
      some temporal relief of hormonal sensitivity of anuran metamorphosis.

PMID- 8274703
TI  - [The microcirculatory bed of the rabbit pinna under increased blood
      concentration].
AB  - Microvessels of rabbit left and right ear chamber and blood samples drawn from
      the internal ear vein in response to hemoconcentration were studied. The apparent
      viscosity of the outflowing blood in the left side was shown to be preserved with
      an increase of hemoconcentration. In the right one episode of increasing
      occurred. The invariance of the total area of perfused microvessels to increased
      hemoconcentration in the right side was fixed, whereas in left side it changed.
      The variation of regional resistance was analysed on the basis of our data
      according to Poiseuille's [correction of Puazeil] equation.

PMID- 8274704
TI  - [The reaction of the nonapeptidergic neurosecretory cells of the hypothalamic
      accessory groups to cold and immobilization stresses in rats].
AB  - Male Wistar rats were subjected to stresses of two different kinds: cooling (2 h
      at 4 degrees C) or immobilization (20 min). In the rat hypothalamus,
      oxytocinergic (OTE) and vasopressinergic (VPE) cells were studied
      immunohistochemically (PAP-method) in following magnocellular accessory groups:
      circular (CG), perifornical (PFG), ventrolateral (VLG), dorsolateral (DLG),
      extrahypothalamic (EHG), and periventricularly localized OTE cells (PVC). In
      cooled rats, sizes of cellular nucleoli increased significantly in both OTE and
      VPE cells of the CG, EHG and PVC indicating activation of hormone production. The
      immobilization stress caused the reverse changes of morphometric characteristics
      in the groups. Signs of VPE cell activation were revealed after both cooling and
      immobilization in the PFG only. The cells of VLG and DLG did not change
      significantly under both stresses. It is concluded that the accessory groups of
      nonapeptidergic cells in the hypothalamus are functionally different and each of
      them is of particular significance in the organism. The role of the accessory
      groups for peripheral endocrine gland regulation is discussed.

PMID- 8274705
TI  - [A morphofunctional study of the hypothalamic postoptic nucleus after
      hypophysectomy, cooling and immobilization in rats].
AB  - Response of the vasopressin (VP) and oxytocin (OT) cells of hypothalamic post
      optical nucleus (PON) was studied in male Wistar rats under various experimental
      conditions. Seven days after hypophysectomy, the majority of both VP- and OT
      cells became pyknomorphic which seemed to be the result of transsection of the
      PON-cell axons and indicated that the PON-cells released neurohormones from the
      posterior pituitary into the blood. When rats were cooled (2 h at 4 degrees C),
      the size of nucleoli in VP-cells diminished significantly, but in rats stressed
      by severe immobilization (20 min) these cells revealed clear signs of activation.
      In contrast to that, no changes were observed in the OT-cells after these
      treatments. The functional relation of the PON and thyroid gland is discussed.

PMID- 8274706
TI  - [The comparative characteristics of the antiatherogenic effect of xymedon and
      parmidine].
AB  - We've studied xymedon (30 mg/kg, 12 m) and parmidin (pyridinolcarbamate 30 mg/kg,
      12 m.) effects on the development of experimental cholesterol atherosclerosis on
      rabbits. It was demonstrated that after the use of xymedon aorta damage reduces
      twice. Xymedon also prevents accumulation of cholesterol and fatty degeneration
      of the liver. Antiatherogenic effect of xymedon resulted comparable with the
      effect of parmidin. As it was demonstrated in the present investigation and in
      the previous ones in contrast to parmidin, xymedon normalizes the lipoproteins
      balance owing to increase of HDL cholesterol. It also has regenerative activity
      on endotheliocytes and immunomodulator properties. That can be of great
      importance for the anti-atherosclerotic effects of the medicine.

PMID- 8274708
TI  - [Individual differences in the reactions to acute stress related to behavioral
      types. The structural changes in the brain].
AB  - Structural alterations in the brain after stress were studied in rats with
      different behavior type in open field and forced swimming tests. The most typical
      brain reaction to acute stress was a combination of reactive (hypertrophy and
      fission of mitochondria, hyperplasia of rough reticulum) and destructive
      (disintegration of mitochondria and rough reticulum) alterations which were
      different in rats with various behavior types. Thus, in rats with the active type
      of behavior showing the greatest resistance to stress (see report 1) the reactive
      processes were more manifest, while the the rats with the passive type of
      behavior showing lower resistance to stress developed destructive processes. Rats
      of the middle group with the least resistance to stress differed from the other
      two groups by vague structural alterations, i.e. by the lack of evident
      predominance of any definite process. It is assumed that individual differences
      in the resistance to acute stress are associated with individual differences in
      the manifestation of reactive alterations in the brain which can be regarded as a
      structural component of the urgent adaptation to stress.

PMID- 8274707
TI  - [The morphological mechanism of the development of myosatellitocytes from the
      structural elements of the muscle fiber during increased functional activity of
      the skeletal muscles].
AB  - Under increased muscular activity in some muscular fibers disintegration areas of
      myofibrillar apparatus has been revealed. Migration of myonuclei into these
      microregions starts the mechanism of their segregation due to plasmolemma
      produced from the reticulum sarcoplasmaticum and triad systems surface. After
      plasmolemma production in "sarcocytes" intensive development and differentiation
      of organellae occur. As a result of differentiation "sarcocytes" transform in to
      myosatellitocytes of type-2 and migrate under lamina externa muscular fibers. So,
      a hypothesis about formation of myogenic tissue's cellular phase from the
      myosymplastic one has been confirmed.

PMID- 8274709
TI  - [The mechanism of the development of the synapse as the basis for its
      involution].
AB  - The electron microscopic investigation of human brain synaptic organization in
      normal aging and in ischemic heart pathology in different life periods was
      performed. A significant quantity of desmosome-like and mixed contacts was shown.
      Their ultrastructural organization was similar to that of developing synapses
      during prenatal ontogenesis and in newborn rats. The analysis of the experimental
      results suggests that an appearance of desmosome-like contacts in the human brain
      results from synapse involution. This is supported by the observation of
      formation of mixed contacts which may be a transitional stage between symmetrical
      or asymmetrical specialized synapse and desmosome. Thus, the mechanism of
      synaptic involution appears to be a mirror reflection of the mechanism of its
      development.

PMID- 8274710
TI  - [Sex differences in the grooming parameters in rat ontogeny].
AB  - The analysis of sex differences in the total amount of grooming movements showed
      that sex differences first appeared in the 2nd month of rats' life because of
      great increase of grooming movements in females. During the 1st month of immature
      rat life sex differences were observed in the rate of increase of frequency of
      grooming movements and of their duration.

PMID- 8274711
TI  - [The effect of carnosine on the intracellular pH in cultured human embryonic lung
      fibroblasts].
AB  - Dipeptide carnosine effect on fibroblast proliferation was assessed by changes in
      intracellular pH (pHi) in human cultivated lung embryonal fibroblasts. pHi was
      defined by means of fluorescein diacetate (FDA) during 1-7 days of the culture
      growth. The investigation showed changes in pHi depending on dipeptide
      concentration and the presence of additives in it. In some cases rat carnosine
      caused acidification of cells assumed to be a reaction and the presence of
      additives of metals in the drug. Sometimes an increase in pHi was observed
      immediately or shortly after acidification of the cells. In this case dipeptide
      was assumed to have a stimulating influence on fibroblast pHi due to a low
      concentration of additives in the drug and fast adaptation of cells. Purified
      carnosine increased pHi immediately after its addition to the incubation medium.
      The maximum effect was observed after addition of 10 mkg/ml carnosine, delta of
      pHi was on the average of 0.22. An increase of carnosine concentration to 50-100
      micrograms/ml did not lead to increased effect. So, the increase of fibroblast
      pHi upon introduction of carnosine may be one of the causes of activation of
      fibroblast proliferation. The pH-metry method may be recommended as an express
      test for the evaluation of the degree of a drug purification.

PMID- 8274712
TI  - [Laser correlational spectroscopy in studying the subfractional composition of
      the blood plasma of patients with gastric hemorrhage, craniocerebral trauma and
      intoxication].
AB  - LCS presents information on the size distribution of particles in analysed
      objects. LCS of blood plasma was performed in 26 patients with stomach bleedings,
      19 with brain injuries, 13 with chronic hepatitis, 149 with chronic chlorophos
      intoxication and 45 healthy subjects. Spectra of blood plasma from patients with
      stomach bleeding differed significantly from those of healthy subjects. Spectra
      of blood plasma from patients with brain injuries differed from those of alcohol
      poisoning patients. The size distribution of particles in the blood plasma
      alcohol poisoning patients was similar to that of the patients with chronic
      hepatitis or chronic chlorophos intoxication perhaps because of liver function
      disturbances in all these cases. These results allow LCS to be offered as a
      diagnostic method.

PMID- 8274713
TI  - Modification of opioid receptors and uncoupling of receptors from G proteins as
      possible mechanisms underlying suppression of opioid binding by cholecystokinin
      octapeptide.
AB  - Previous studies have shown that central cholecystokinin (CCK) octapeptide (CCK
      8) suppresses the binding of opioid receptors to the opioid agonists. In the
      present study, tritium-labelled etorphine (opioid agonist) and naloxone (opioid
      antagonist) as well as guanosine-5'-0-(3-thiotriphosphate) (GTPrS) were used to
      investigate the possible mechanisms underlying the suppression of opioid binding
      by CCK-8 in rat brain membranes. CCK-8 at a concentration range of 10 nmol/L to 1
      mumol/L dose-dependently suppressed the binding of [3H]-naloxone to opioid
      receptors, with a decrease in Bmax and an increase in Kd. GTPrs was found to
      reduce the affinity of [3H]-etorphine binding in a dose-dependent manner. This
      effect was markedly diminished in the presence of 10 nmol/L of CCK-8. These
      results suggest that CCK-8 might suppress opioid binding at both the receptor and
      post-receptor levels; that is, 1) by reducing the number and affinity of opioid
      receptors, and 2) by uncoupling opioid receptors from their G proteins.

PMID- 8274714
TI  - The role of activated neutrophils and free radical in the pathogenesis of
      pulmonary hypertension.
AB  - In in situ perfused rat lungs, it was demonstrated that the perfusing pressure
      and permeability of pulmonary capillaries were obviously increased after
      activated neutrophils (PMNs) were added to the perfusate. The effect of free
      radicals generated by the xanthine-xanthine oxidase system on isolated rabbit
      pulmonary arterial ring tension was also observed, and the contractile response
      was found to be dose dependent: The smaller the vessel diameter, the higher the
      contractile response. Superoxide dismutase and catalase were able to obviously
      attenuate the contractile response. The response was endothelium independent, and
      was influenced neither by indomethacin (cyclooxygenase inhibitor) nor by
      nordihydroguaiaretic acid (lipoxygenase inhibitor), while removal of Ca from the
      bath solution or addition of the protein kinase C (PKC) inhibitor "H7" or an
      antiinflammatory drug (764-3, the effective component of Radix Salvia
      miltiorrhizae) could significantly inhibit the contractile response. The results
      suggest that activated PMNs may play an important role in the pathogenesis of
      pulmonary hypertension.

PMID- 8274715
TI  - Effect of intra-vas deferens injection of gossypol-polylactic acid on fertility
      and spermatogenesis in rats.
AB  - In order to reduce gossypol's side effects, we applied a controlled drug release
      system. In this system gossypol is carried on a polymer of polylactic acid which
      controls drug release and can also be injected into the vas deferens so that the
      drug can act continuously and directly on spermatogenesis. We used a single dose
      of gossypol-polylactic acid (0.35 mg/0.1 ml for each vas deferens) which is only
      0.2% of the usual antifertility dose. Fertility tests showed that male rats
      became infertile 4 weeks after intravasal injection of gossypol-polylactic acid.
      Gross and microscopic findings in the heart, liver, kidneys and lungs revealed no
      evidence of pathologic change. Treated rats gained body weight as fast as did the
      controls. The majority of spermatozoa showed breakage of the axial fibers,
      indicating that gossypol had diffused into the testes. The fertility of the
      treated rats recovered four to eight months after treatment. Gossypol-polylactic
      acid injected into the vas deferens exhibited a low degree of toxic side effects
      and a high antifertility activity, and is therefore an important approach to
      decreasing the side effects while enhancing the antifertility specificity of
      gossypol.

PMID- 8274716
TI  - Nude mouse interim host model for human parathyroid grafts. Part III. Mechanism
      of modification of allograft antigenicity.
AB  - The alterations of number and DR antigen expression of antigen presenting cells
      (APCs) in human PTG grafts during the interim hosting period were analyzed. The
      results were as follows: 1) In C-PTG grafts, the APC number was reduced obviously
      within 100 days in the interim host. In F-PTG and A-PTG grafts, the APC number
      was increased at 30 d of interim hosting, and then decreased gradually. 2) No
      obvious change in D-related (DR) antigen expression of individual APCs was seen
      in C-PTG and F-PTG grafts. In A-PTG grafts, DR antigen expression was increased
      at 30 d of interim hosting, but then dropped gradually and asynchronously.

PMID- 8274717
TI  - Nude mouse interim host model for human parathyroid grafts. Part IV. Human PTG
      xenograft rejection in a mouse B lymphocyte system.
AB  - An interim host model for human parathyroid gland (PTG) grafts has been
      established. In this experiment, the proliferation of mouse blood vessels and
      infiltration of mouse B lymphocytes into human PTG grafts were successively
      observed. The results showed that within 10 d of interim hosting, when PTG grafts
      were still nourished by permeable factors, scattered mouse B lymphocyte
      infiltration was already apparent. As time went by, B lymphocyte infiltration and
      IgG secretion became more obvious. At 60-90 d interim hosting, an intact human
      mouse tissue "chimera" was formed. Thereafter, human PTG grafts were gradually
      fragmented and absorbed. The theoretical significance and clinical value of this
      rejection phenomenon are discussed.

PMID- 8274718
TI  - Bacterial plaque and enamel caries.
AB  - A series of five experiments were done to investigate the relationship between
      bacterial plaque and enamel caries: 1) Topographic examination of the
      distribution of plaque and initial enamel caies demonstrated a close relationship
      between these two. 2) By using a method of caries-like lesion production in
      vitro, it was shown that plaques collected from caries-active, caries-free and
      periodontal diseased persons could produce caries-like lesions, but the lesions
      produced by periodontal plaque were shallower than others. 3) In testing the
      cariogenicity of different phases of plaque, it was found that the liquid phase
      is the active phase in the carious process. 4) Examination of the proteolytic
      action of plaque fluid showed no reaction between plaque fluid and proteinous
      substances in enamel. This result does not support Gottleib's proteolysis theory,
      especially as it applies to enamel cares. 5) An in vitro model of multibacterial
      artificial plaque was established. Caries-like lesions were produced in this
      model, and the structure of the plaque was found to be very similar to that
      produced naturally.

PMID- 8274719
TI  - An analysis of the correlation between angiographic and clinical findings in
      cerebral arteriovenous malformations.
AB  - One hundred and sixty-seven cases of cerebral arteriovenous malformations (AVMs)
      confirmed by digital subtract angiography (DSA) and surgery were analyzed to find
      the correlation between clinical and angiographic findings with regard to sex,
      age, size of angioma, and number of drainage veins and feeding arteries.
      Statistical analysis showed that the risk of hemorrhage was highest in small AVMs
      with only one drainage vein, and decreased with increases of volume and number of
      AVMs. Statistics also demonstrated that small AVMs usually have one drainage vein
      and so have a high risk of hemorrhage.

PMID- 8274720
TI  - Treatment of herpes zoster: recombinant alpha-2a-interferon versus acyclovir and
      vitamin therapy. Clinical Study Group on Interferon.
AB  - The efficacy of r-interferon alpha 2a (IFM) versus acyclovir (ACV) and vitamin
      therapy in the treatment of herpes zoster is reported. A total of 305 patients
      were randomly divided into 3 groups. One million units of IFN were administered
      i.n. once a day for 6 days in 223 cases, oral ACV 200 mg five times daily for 7
      days in 34 cases, and vitamin B12, B1 and B2 therapy at conventional doses for 7
      14 days in 48 cases. The results showed that both IFN and ACV could reduce pain
      in patients with herpes zoster and cut the total duration of symptoms, in
      comparison with vitamin therapy (P < 0.01). In the IFN group, 45 patients (20.2%)
      experienced side effects, including mild fever in 35 cases (15.7%) and a slightly
      depressed leukocyte count or increased serum ALT level (3 cases each). In the ACV
      group, one complained of discomfort in the gastroenteric tract, and another
      patient reported lumbodynia.

PMID- 8274721
TI  - Surveillance and care of four Chinese hemophiliacs with human immunodeficiency
      virus (HIV) infection.
AB  - Four Chinese hemophiliacs with HIV infection have been followed up in Zhejiang
      Province since 1985. A plan for optimal care of HIV seropositive patients was
      proposed, including surveillance and care; clinical follow-up and preventive
      education of asymptomatic HIV seropositive patients; keeping the disease
      confidential so as not to stir up unnecessary social unease; propaganda and
      health education about acquired immunodeficiency syndrome (AIDS); treatment with
      traditional Chinese medicines; and regular surveillance of family members and
      medical personnel. This plan is regarded as feasible and effective for the
      prevention and control of AIDS in China.

PMID- 8274722
TI  - The influence of electromagnetism on genes.
AB  - This paper reviews recent clinical and experimental work in the area of
      bioelectromagnetics. New insights into the possibilities of electromagnetism in
      therapeutics as well as diagnostics are proposed.

PMID- 8274723
TI  - Thymic carcinoid tumor--a report of 7 cases.
AB  - The thymic carcinoid tumor is a rare neoplasm which is often clinically
      misdiagnosed as thymoma. But the two differ in origin, biological behavior,
      accompanying syndromes, pathological features, and prognosis. The characteristics
      of the thymic carcinoid tumor are: difficulty in diagnosis, high malignancy,
      frequent recurrence and extrathoracic metastasis over a prolonged period
      postoperatively. Complete surgical resection of original and recurrent tumors is
      the important treatment. Microscopic, electron microscopic and
      immunohistochemical examinations may be required in making an accurate
      pathological diagnosis. This paper reports 7 cases of thymic carcinoid tumor.

PMID- 8274724
TI  - Effects of iontophoretically applied morphine on respiration related units in the
      medial part of the nucleus retrofacialis region in rats.
AB  - The effects of morphine on 108 spontaneously discharging units in the medial part
      of the nucleus retrofacialis (mNRF) were studied in 13 SD rats anesthetized with
      urethane and allowed to breathe spontaneously. A 5-barrelled microelectrode was
      inserted into the mNRF region to record discharges of respiration related units
      (RRUs) and nonrespiration related units (NRRUs), and then morphine was
      administered by iontophoresis. Among the 27 inspiration related units (InRUs)
      recorded, morphine exerted an inhibitory effect on 8 units and an excitatory
      effect on 6 units; while among the 36 expiration related units (ExRUs), the
      excitatory effect was much more obvious than the inhibitory effect (12 vs 2).
      This difference was statistically significant. The results revealed a difference
      between the effects of morphine on InRUs and ExRUs in the mNRF region. The
      excitatory effect of morphine on ExRUs in the mNRF region might play a role in
      the mechanism by which morphine depresses respiration.

PMID- 8274725
TI  - A strain of urease negative Cryptococcus neoformans isolated from the environment
      in China.
AB  - This is the first report of a strain of urease negative Cryptococcus neoformans
      isolated from the environment in China. The colonies of this isolate showed brown
      pigmentation on cornmeal agar with 300 micrograms/ml caffeic acid, but failed to
      hydrolyze urea. Microbiological identification and pathogenicity tests in mice
      confirmed this as a strain of C. neoformans. A similar strain had reportedly been
      isolated from an AIDS patient.

PMID- 8274726
TI  - Detection of anti-SSB antibodies in patients with rheumatic diseases.
AB  - Anti-SSB antibodies were measured by ELISA in patients with various kinds of
      connective tissue diseases using SSB antigen purified from fresh rabbit thymus.
      The SSB antigen reacted with anti-SSB standard serum, and the positive rates in
      SS, SLE, RA, PBS and MCTD were 55.1%, 48.3%, 32.8%, 30.8% and 26.3%,
      respectively. The titers of anti-SSB antibodies were higher in SS and SLE
      patients than in other connective tissue disease patients. However, 10% of normal
      individuals were found to have anti-SSB antibodies with low titers. The anti-SSB
      antibodies detected were mainly of IgG isotype. Preliminary analysis of clinical
      data showed no relationship between anti-SSB and systemic involvement in SS.

PMID- 8274727
TI  - The beginnings of the Peking Union Medical College.

PMID- 8274728
TI  - Evolving understanding of the cellular defect in polycythemia vera: implications
      for its clinical diagnosis and molecular pathophysiology.

PMID- 8274729
TI  - Acute promyelocytic leukemia: from genetics to treatment.

PMID- 8274730
TI  - Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating
      IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55.
AB  - The aim of this study was to investigate whether interleukin (IL)-6 induces the
      production of IL-1 and tumor necrosis factor (TNF) antagonists. Serial plasma
      samples were obtained from cancer patients participating in phase I and II trials
      of recombinant IL-6 administered as a 120-hour continuous intravenous (IV)
      infusion. Plasma IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor p55
      (TNFsRp55) levels were measured by specific radioimmunoassays (RIAs). IL-1Ra
      levels increased rapidly, reaching peak values (9.6 +/- 1.7 ng/mL) within 2 to 4
      hours of beginning treatment. Thereafter, levels promptly declined, reaching near
      baseline within 24 hours despite continuation of IL-6. TNFsRp55 plasma levels
      increased within 4 to 8 hours after initiating treatment and increased
      progressively throughout the duration of therapy. IL-1 beta and TNF-alpha plasma
      levels were below the detection limit in all samples tested. Peripheral blood
      mononuclear cells (PBMC) exposed to IL-6 produced only small amounts (1.56 +/-
      0.3 ng/mL) of IL-1Ra, even in the presence of exogenous soluble IL-6 receptor
      (gp80). TNFsRp55 levels measured in the supernatants of IL-6-stimulated PBMC were
      below the detection limit of the assay. Macrophages generated by culturing
      monocytes in granulocyte-macrophage colony-stimulating factor (GM-CSF) were much
      more responsive to IL-6 than freshly isolated unfractionated or adherent PBMC and
      synthesized almost as much IL-1Ra when stimulated with IL-6 as with endotoxin.
      These results suggest that the antinflammatory properties of IL-6 may be due; in
      part, to the induction of IL-1Ra synthesis and the release of soluble TNF
      receptors. Our findings also suggest that tissue macrophages may be an important
      source of IL-6-induced IL-1Ra.

PMID- 8274731
TI  - Granulocyte colony-stimulating factor receptor mRNA upregulation is an immediate
      early marker of myeloid differentiation and exhibits dysfunctional regulation in
      leukemic cells.
AB  - The identification of early markers of myeloid differentiation can facilitate an
      understanding of how differentiation is arrested in leukemogenesis. Using murine
      bone marrow and the granulocyte-precusor cell line 32Dc13, we show that message
      for the granulocyte colony-stimulating factor receptor (G-CSFR) is upregulated by
      G-CSF in an immediate early fashion that is specific to the differentiation
      pathway and is antagonized by interleukin-3. We further show that G-CSFR message
      is superinduced by cycloheximide and that these patterns of regulation are
      altered in leukemic cell lines. In particular, the v-abl oncogene product
      supresses both ligand-mediated upregulation and superinduction of the G-CSFR
      gene.

PMID- 8274732
TI  - Antithrombin-Gly 424 Arg: a novel point mutation responsible for type 1
      antithrombin deficiency and neonatal thrombosis.
AB  - Inherited type 1 antithrombin (AT) III deficiency is characterized by a decrease
      of immunoreactive and functional protein levels to about 50%. The disorder is
      associated with a significantly increased risk of thromboembolism. We have
      investigated the molecular basis of type 1 AT deficiency in a Belgian family. The
      diagnosis of the disease was primarily made in a newborn girl with unusually
      severe thrombotic complications. Using the polymerase chain reaction and single
      strand conformation polymorphism analysis, followed by direct sequencing of AT
      gene fragments, we identified a novel point mutation in exon 6. We detected a G
      to C substitution in the first position of codon 424 leading to a glycine to
      arginine substitution. The modification at this highly conserved position in the
      serine protease inhibitor gene family probably leads to an unstable mutant-gene
      product. The mutation creates a unique restriction site for the enzyme Hha I in
      exon 6. This change permitted a rapid and accurate screening of the kindred with
      identification of the molecular defect in five other family members.

PMID- 8274733
TI  - Effect of human recombinant cytokines on the induction of macrophage procoagulant
      activity.
AB  - A panel of human recombinant cytokines was tested for induction of procoagulant
      activity (PCA) in human monocyte-derived macrophages. Nonadherent culture
      conditions were used, and PCA was determined with whole cells rather than cell
      lysates. It was assured by Limulus amebocyte lysate assay that tested cytokines
      displayed low levels of endotoxin activity within the range of biologic activity.
      Additional evidence to rule out an endotoxin effect was provided by heat
      inactivation experiments. Interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1
      beta), and tumor necrosis factor-alpha (TNF-alpha) were strong macrophage PCA
      inducers. The low level of PCA induced by IL-2, granulocyte-macrophage colony
      stimulating factor (GM-CSF), M-CSF, IL-4, IL-6, IL-10, and IFN-alpha could not be
      distinguished from that induced by traces of endotoxin contaminating the
      preparations. Transforming growth factor-beta decreased constitutively expressed
      PCA within 24 hours of exposure. PCA induced by IFN-gamma, IL-1 beta, and TNF
      alpha depended largely on tissue factor expression, as evidenced by experiments
      with factor X-deficient plasma and antitissue factor antibodies. In macrophages
      subcultured in adherence, IL-1 beta was a strong PCA inducer, whereas IFN-gamma
      and TNF-alpha promoted little PCA increase. This observation and different
      kinetics of PCA induction suggested that mechanisms of PCA induction are distinct
      for the three cytokines. Thus, we showed that well-characterized cytokines
      critically involved in the promotion of cell-mediated antimicrobial
      defense/delayed-type hypersensitivity and considered for clinical application
      promote local fibrin deposition by a direct effect on macrophages.

PMID- 8274734
TI  - Alterations of the p53 tumor suppressor gene in diffuse large cell lymphomas with
      translocations of the c-MYC and BCL-2 proto-oncogenes.
AB  - Diffuse large cell lymphomas are aggressive tumors of B-cell origin. In some
      cases they arise from low-grade follicular lymphomas carrying the t(14;18)
      translocation, an event that leads to the overexpression of the BCL-2 gene
      product. More frequently, however, they lack the t(14;18) translocation.
      Rearrangements of the c-MYC proto-oncogene and mutations of the p53 tumor
      suppressor gene have also been documented in these lymphomas. This study examines
      the extent to which alterations in the BCL-2, c-MYC, and p53 genes co-exist
      within individual lymphomas. Eight diffuse large cell lymphoma cell lines and 11
      diffuse large cell lymphoma tumors were assessed for genetic alterations in these
      three genes. Our results indicate that there is a heterogeneity in the
      oncogene/suppressor gene profile among diffuse large cell lymphomas. Two cell
      lines and one tumor carried alterations in all three genes, one cell line carried
      alterations of c-MYC and p53, and one primary tumor and one cell line carried p53
      mutations and the t(14;18). Single alterations of BCL-2 and p53 were also
      observed. Another cell line had no alterations in any of these genes. The
      heterogeneity indicates that varied mechanisms may be involved in the generation
      of diffuse large cell lymphomas.

PMID- 8274735
TI  - Consistent loss of the D5S89 locus mapping telomeric to the interleukin gene
      cluster and centromeric to EGR-1 in patients with 5q- chromosome.
AB  - Interstitial deletions of the long arm of chromosome 5 are common in a number of
      disorders of leukemic and preleukemic myeloid disorders. Although the limits of
      these deletions vary among patients, a region of cytogenetic overlap that
      includes band 5q31 is deleted consistently, suggesting loss of 5q31 loci critical
      for normal myeloid differentiation and leukemogenesis. An anonymous genomic DNA
      segment D5S89, previously mapped to 5q21-31, detects consistent loss of alleles
      in cases showing the 5q- chromosome at presentation or relapse. Analysis of a
      panel of natural-deletion somatic-cell hybrids in conjunction with irradiation
      hybrids containing fragments of human chromosome 5q shows that the D5S89 locus is
      telomeric to the interleukin (IL) genes (IL-3, IL-4, IL-5, IL-9, and granulocyte
      macrophage colony-stimulating factor [GM-CSF]) and interferon response factor-1
      (IRF-1) gene and centromeric to the early response transcription factor (early
      growth response gene-1 [EGR-1]) on 5q31. To further define the principal region
      of loss, we have isolated and characterized yeast artificial chromosomes (YACs)
      spanning D5S89. The presence of several CpG islands within the 300-kb YAC is
      suggestive of multiple transcription units. However, IL-4, IL-5, IRF-1, IL-3, GM
      CSF, and EGR-1 genes were not detected in the YAC clone spanning D5S89, implying
      that none of these genes are in the vicinity of the D5S89 marker. Further
      characterization of these YACs should facilitate the isolation of novel candidate
      genes that may play a role in the evolution of the abnormal phenotype associated
      with 5q- chromosome.

PMID- 8274736
TI  - Molecular cloning of the breakpoint for 3q27 translocation in B-cell lymphomas
      and leukemias.
AB  - Reciprocal exchanges between chromosomal region 3q27 and three loci of the Ig
      genes have been reported in cases of B-cell type non-Hodgkin's lymphoma. We have
      cloned a region containing a breakpoint junction of 3q27 from a cell line
      established from a patient with Burkitt's lymphoma carrying t(3;22)(q27;q11). The
      region cloned was shown to contain an Ig lambda light chain gene fused to a gene
      on chromosome 3q27. This finding was subsequently confirmed by fluorescence in
      situ hybridization. Extra nucleotides were present at the joining site. The
      heptamer-like and nonamer-like sequences separated by an intervening 24 bp were
      present in the region corresponding to the breakpoint of 3q27, suggesting that a
      misrecombination in Ig gene rearrangement may be involved in the translocation.
      Southern blot analysis with a 3q27-specific probe showed rearrangements in three
      additional patients with B-cell malignancies with the t(3;14)(q27;q32). The
      breakpoints of all four cases clustered within a limited 3-kb region on
      chromosome 3q27. The region of 3q27 involved in the translocation was designated
      as the BCL5 locus. The transcripts from the BCL5 locus were detected in normal
      tissues and hematopoietic cell lines, and the increased expression of transcript
      of aberrant size was detected in the established cell line carrying t(3;22).
      These observations suggest that a gene located at 3q27 is involved in the
      translocation and that its deregulation plays a role in the malignant
      transformation of B cells.

PMID- 8274737
TI  - The bcl-2 oncogene in Hodgkin's disease arising in the setting of follicular non
      Hodgkin's lymphoma.
AB  - Expression of the bcl-2 proto-oncogene on chromosome 18 is deregulated by the 14;
      18 chromosomal translocation, an abnormality that is consistently associated with
      follicular non-Hodgkin's lymphomas (NHL). Because bcl-2 is believed to function
      by prolonging cell survival rather than by increasing proliferation, the presence
      of t(14; 18) in Hodgkin's disease (HD) would have profound implications for the
      pathogenesis of this neoplasm. We evaluated 32 cases of HD for t(14; 18) by
      polymerase chain reaction (PCR). These results were correlated with expression of
      bcl-2 oncogenic protein by Hodgkin cells and with the presence of Epstein-Barr
      virus (EBV), as determined by immunohistochemistry or in situ hybridization. PCR
      provided evidence of t(14; 18) in only 2 HD cases (6%), both of which were
      associated with a prior history of follicular lymphoma, and both of which were
      among the 7 cases (22%) with strong bcl-2 expression in Hodgkin cells. In at
      least 1 of the cases, the translocation involved identical chromosomal
      breakpoints in both types of lymphoma. Furthermore, 7 additional cases of
      combined follicular NHL and HD showed strong bcl-2 staining in Hodgkin cells.
      Although EBV was detected in 6 of 30 cases, it was not associated with t(14; 18)
      and usually not with strong bcl-2 expression. These results suggest that a small
      proportion of HD cases might evolve from follicular NHL, possibly through
      molecular events superimposed on the t(14; 18). High-level bcl-2 expression in
      Hodgkin cells is a potentially useful but not definitive marker for these cases.

PMID- 8274738
TI  - The 47-kD protein increased in neutrophil actin dysfunction with 47- and 89-kD
      protein abnormalities is lymphocyte-specific protein.
AB  - A male child born of related parents suffered recurrent infections because of
      neutrophil actin dysfunction with increased amounts of a 47-kD protein and
      decreased amounts of an 89-kD protein (NAD 47/89). The patient and family members
      were studied to define the nature of the abnormal proteins and to examine their
      role in the functional defects of neutrophil actin dysfunction (NAD) 47/89
      polymorphonuclear neutrophils (PMNs). NAD 47/89 PMNs are defective in motility,
      microfilamentous cytoskeletal structure, and formyl peptide-induced actin
      polymerization and express increased amounts of a 47-kD protein and decreased
      amounts of an 89-kD proteins intermediate abnormality in amount of 47-kD and 89
      kD proteins in PMNs from parents and a female sibling suggest the disease is an
      autosomal recessive disorder. Immunoblots with monoclonal antibody (MoAb1) and
      polyclonal antibody raised to 47-kD protein showed the 89-kD protein is
      antigenically distinct from the 47-kD protein and the 89-kD protein is not
      gelsolin. 125I-actin binding to one-dimensional (1 D) and 2 D gels of PMN
      proteins from NAD 47/89 proband, family members, and controls showed the 47-kD
      protein binds actin, is acidic (pl = 4.5 to 4.7), is recognized by the MoAb1,
      exists on 2-D gels as three distinct actin binding species (MWapp 52 kD, 47-kD,
      and 44-kD), and is present in control PMNs in lesser amount than in PMNs of NAD
      47/89 proband or parents. Immunoaffinity purification of the 47 kD actin binding
      protein on MoAb1 matrix yielded a multimolecular complex with proteins of MWapp
      180 kD, 71 kD, 47 kD and actin. Cloning, sequencing, and expression of a 1.58-kb
      cDNA selected for MoAb1 reactivity from a HL60 expression library and
      microsequence of native PMNs, 47-kD actin binding protein showed the
      overexpressed 47-kD protein is lymphocyte-specific protein 1 (LSP1), which is a
      known actin binding protein. The results show LSP1 is expressed in PMNs and
      suggest overexpression of LSP1 is related to the motility and cytoskeletal
      abnormalities in NAD 47/89 PMNs.

PMID- 8274739
TI  - Denaturing interaction between sickle hemoglobin and phosphatidylserine
      liposomes.
AB  - It is hypothesized that abnormal interaction between sickle hemoglobin (HbS) and
      erythrocyte membrane lipid might promote deposition of denatured hemoglobin
      (hemichrome) on the membrane. We compared the interaction of HbS and normal HbA
      with large unilamellar phosphatidylserine (PS) liposomes under low salt/pH
      conditions. Admixture of oxyHb and dioleoyl-PS resulted in loss of absorbance at
      412 nm, the apparent first order rate constant for which was .25 +/- 0.02 hour-1
      for HbA and .85 +/- 0.18 hour-1 for HbS. This was ascribable largely to formation
      of metHb and hemichromes and was accompanied by some actual transfer of heme from
      hemoglobin to lipid phase. By comparison, admixture of oxyHb with liposomes made
      from bovine brain PS having unsaturated acyl chains promoted even faster
      absorbance loss if the starting liposomal material contained detectable
      peroxidation by-product. In such cases, actual heme destruction developed with
      accompanying liberation of free iron and promotion of lipidperoxidation.
      Fluorescence quenching experiments indicate that hemoglobin/lipid interaction is
      characterized by very rapid initial electrostatic interaction, followed by
      development of irreversible changes. Similar changes still occur under conditions
      of physiologic salt/pH, but they develop much more slowly. The 3.4-fold faster
      oxidation of HbS versus HbA on lipid observed here represents an additional
      augmentation of the disparity in oxidation rates for hemoglobins in solution (1.7
      fold faster for HbS than for HbA) observed previously. The accelerated promotion
      of Hb denaturation resulting from lipid contact may help explain deposits of
      hemichrome on sickle red blood cell membranes, particularly because these cells
      are in double jeopardy by virtue of having both the mutant HbS and abnormal
      amounts of peroxidized membrane lipid.

PMID- 8274740
TI  - Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5,
      encodes a Kruppel-like zinc-finger protein.
AB  - Chromosomal translocations involving band 3q27 are the recently described
      nonrandom cytogenetic abnormalities in B-cell malignancies. We have previously
      cloned the breakpoint region of 3q27, designated as the BCL5 locus, from the B
      cell line carrying the t(3;22). The cDNA for the BCL5 gene was cloned from the
      human liver cDNA library. The nucleotide sequencing analysis showed that the BCL5
      gene encodes a potential transcription factor containing six repeats of the Cys2
      His2 zinc-finger motif resembling the Drosophila segmentation gene Kruppel. The
      calculated molecular weight was 78.8 kD, which was supported by an in vitro
      transcription and translation experiment. A part of the sequence was essentially
      identical to that of a genomic fragment, ZNF51, previously reported to be located
      at 3qter. The translocation occurred in the 5' region of the BCL5 gene, and the
      protein-coding exons were fused to the Ig-lambda gene in a head-to-head
      configuration in the cell line carrying t(3;22). The BCL5 cDNA probe detected a
      major transcript of 3.8 kb in Burkitt's lymphoma cell lines and an aberrant
      transcript in the t(3;22) cell line, whereas no transcript was detected in
      myeloid, monocytoid, erythroid, T-lymphoid, and Epstein-Barr virus-immortalized B
      lymphoblastoid cell lines.

PMID- 8274741
TI  - Detection of hepatitis C virus RNA in peripheral blood mononuclear cells of
      infected patients by in situ hybridization.
AB  - We used in situ hybridization to detect hepatitis C virus (HCV) infection of
      peripheral blood mononuclear cells (PBMNC) from 11 patients with chronic active
      hepatitis. Using 35S-labeled HCV-RNA probe, HCV-RNA-positive and -negative
      strands were observed in unstimulated PBMNC from three patients, all of whom were
      receiving immunosuppressive drugs after orthotopic liver transplantation (OLT).
      HCV-RNA sequences were also identified in PBMNC from three patients who were not
      undergoing immunosuppression, after stimulation with either phytohemagglutinin
      (PHA) or pokeweed mitogen (PWM). In contrast, HCV-RNA was not found in the
      remaining five patients, who had not undergone OLT and whose cells were not
      stimulated with mitogens. These results show that mononuclear cells can be
      infected by HCV and that mitogenic stimulation of infected cells increases HCV
      RNA replication.

PMID- 8274742
TI  - Thrombocytopenia after bone marrow transplantation caused by a recipient origin
      Br(a) allo-antibody: presence of mixed chimerism 3 years after the graft without
      hematologic relapse.
AB  - We report a case of mild, clinically asymptomatic, immune thrombocytopenia after
      allogenic bone marrow transplantation (BMT) for chronic myeloid leukemia (CML)
      caused by the presence of a recipient-origin Br(a) antibody that recognized the
      donor platelets. Although the antibody titer decreased, it remained detectable
      more than 3 years after BMT. Chimerism studies were performed combining
      cytogenetics, blood cell phenotype studies, and genomic amplification of
      hypervariable sequences. Cytogenetic studies and molecular analysis of peripheral
      blood cells, purified B- and T-lymphocyte subpopulations, and bone marrow
      colonies showed the hematopoiesis to be of donor origin, but absorption-elution
      experiments with peripheral RBCs showed a small amount of recipient RBCs. The CML
      chimeric transcript was also detected by means of polymerase chain reaction on
      samples collected until day +867 post-BMT. This case shows that recipient-origin
      platelet alloantibodies can cause thrombocytopenia after BMT and that the
      persistence of small numbers of recipient cells (even leukemic) is not
      necessarily associated with hematologic relapse.

PMID- 8274743
TI  - Frequent HLA class I and DP sequence mismatches in serologically (HLA-A, HLA-B,
      HLA-DR) and molecularly (HLA-DRB1, HLA-DQA1, HLA-DQB1) HLA-identical unrelated
      bone marrow transplant pairs.
AB  - The rates of graft-versus-host disease (GVHD) and rejection are significantly
      higher among recipients of unrelated donor marrow (BM) than in recipients of
      marrow from HLA-identical siblings, even when donors and recipients are mixed
      lymphocyte culture (MLC) compatible and serologically and Dw identical. It has
      been hypothesized that phenotypically silent HLA class I and DP sequence
      mismatches might be associated with these differences, but little is known about
      their incidence. We have sequenced the HLA-A, HLA-B, HLA-C, HLA-DPA1, and HLA
      DPB1 genes expressed by 12 unrelated marrow transplant pairs, 11 of whom were
      molecularly matched at DRB, DQA1, and DQB1 loci. Nine of these pairs were also
      HLA-A and HLA-B matched by serology. Six of these nine "HLA-identical" pairs were
      HLA-A (2 of 6), HLA-B (1 of 6), and HLA-C (6 of 6) mismatched at the sequence
      level. The mismatched class I alleles of all these pairs had strikingly different
      sequence motifs in the six specificity pockets of their antigen recognition site,
      and in five pairs they also had sequence differences at positions implicated in T
      cell receptor (TCR) binding. Two of the three pairs who were serologically
      mismatched for one HLA-A or HLA-B antigen were also sequence mismatched at HLA-C.
      Finally, 10 of 11 pairs tested expressed different DP sequences. These data
      indicate that HLA class I, especially HLA-C, and DP sequence mismatches are
      frequent among unrelated subjects defined as HLA identical by current typing
      methods. We speculate that these sequence differences may explain, at least in
      part, the higher incidence of acute GVHD and rejection in unrelated BM
      transplantation as opposed to transplantation between HLA-identical siblings.
      Because of their high frequency, the role of HLA-A, HLA-B, HLA-C, and HLA-DP
      mismatches in transplantation outcome is now amenable to direct study.

PMID- 8274744
TI  - Attenuation of graft-versus-host disease and graft rejection by ex vivo
      immunotoxin elimination of alloreactive T cells in an H-2 haplotype disparate
      mouse combination.
AB  - A mouse anti-interleukin-2 receptor A-chain-specific PC61-immunotoxin (PC61-IT)
      strongly inhibited a primary mixed lymphocyte culture and major
      histocompatibility complex (MHC)-restricted cytotoxicity. The allodepleted T
      cells retained their proliferative and cytotoxic capacities in response to third
      party stimulation, showing that PC61-IT specifically deleted recipient antigen
      specific T-cell clones from the donor mouse. The ability of this specific
      allodepletion to prevent graft-versus-host disease (GVHD) and graft rejection was
      investigated in vivo. IT-depleted, activated parental T lymphocytes (C3H/eB) were
      intravenously injected into lethally irradiated CDF1 mice. GVHD was evaluated
      after 6 days on the severity of gut lesions. PC61-IT-treated cells significantly
      reduced both donor T-cell infiltration and acceleration of epithelial renewal (a
      sensitive index of gut damage) as compared with those for the corresponding
      untreated controls. The effect of selective allo-depletion on prevention of GVHD
      and graft rejection was further studied after MHC-haploincompatible bone marrow
      (BM) transplantation. A significant increase in survival was observed in mice
      receiving 2 x 10(6) T-cell-depleted BM cells and 0.5 x 10(6) PC61-IT-treated T
      cells, because one-third were alive without GVHD (and with stable full or partial
      engraftment) after 100 days, whereas all the mice infused with BM and sham
      treated T cells died within 80 days from GVHD, and all the mice infused with BM
      cells alone rejected grafts. Furthermore, specific tolerance in chimeras towards
      donor cells could be shown. These results as observed in an experimental in vivo
      model corroborate previous results obtained in vitro in humans and lead us to
      consider the use of this selective allodepletion in human BM transplant from
      donors other than identical familial siblings.

PMID- 8274745
TI  - Platelet aggregation abnormalities after cardiopulmonary bypass.

PMID- 8274746
TI  - Disorders of large granular lymphocytes and natural killer-associated cells.

PMID- 8274747
TI  - Lupus anticoagulant and increased thrombin generation in patients with systemic
      lupus erythematosus.

PMID- 8274748
TI  - A 20q deletion originating in a pluripotent stem cell.

PMID- 8274749
TI  - A bone marrow stromal-derived growth factor, interleukin-11, stimulates recovery
      of small intestinal mucosal cells after cytoablative therapy.
AB  - The proliferation of epithelial cells lining the small intestinal mucosa may be
      regulated by microenvironmental signals leading to differentiation of precursor
      cells in the small intestinal crypts. Proliferation of hematopoietic cells within
      the hematopoietic microenvironment is known to be regulated by a growing number
      of glycoprotein growth factors in a hierarchial fashion. We studied the effects
      of administration of the microenvironment-derived hematopoietic growth factor
      interleukin-11 (IL-11) on mice given combination radiation/chemotherapy.
      Treatment of such mice with IL-11 led to significantly increased survival and
      evidence of rapid recovery of the small intestinal mucosa, which is severely
      damaged by these cytoxic agents. This recovery was associated with an increase in
      the mitotic index of crypt cells and an increased frequency of staining of these
      cells with a monoclonal antibody to proliferating cell nuclear antigen, a member
      of the cyclin family of nuclear antigens.

PMID- 8274750
TI  - Human monocytes support factor X activation by factor VIIa, independent of tissue
      factor: implications for the therapeutic mechanism of high-dose factor VIIa in
      hemophilia.
AB  - High doses of recombinant factor VIIa are useful in managing bleeding in
      hemophiliacs with inhibitors. Whether this therapeutic effect of factor VIIa is
      dependent on tissue factor (TF) is a matter of debate. We examined the ability of
      freshly isolated human monocytes (which lack TF) to support the activation of
      coagulation-factor X by factor VIIa. The rate of factor-X activation by factor
      VIIa was accelerated in the presence of monocytes compared with the rate of X
      activation in solution. This activation of factor X on monocytes was saturable
      with a K1/2 of about 400 to 600 pmol/L factor VIIa. The rate of activation was
      not inhibited by an excess of inhibitory anti-TF antibody or a Gla-containing
      fragment of prothrombin. In contrast to monocytes, an endothelial cell line did
      not support activation of factor X by factor VIIa. Our findings suggest that at
      least one cell type can accelerate activation for factor X by factor VIIa in the
      absence of TF. This activity requires higher concentrations of factor VIIa than
      does the TF mechanism. The concentrations of VIIa required are of a similar order
      of magnitude to those required for a therapeutic effect of VIIa in bleeding
      hemophiliacs with inhibitors.

PMID- 8274751
TI  - kat: a high-efficiency retroviral transduction system for primary human T
      lymphocytes.
AB  - We describe a novel retroviral packaging system in which high titer amphotropic
      retrovirus was produced without the need to generate stable producer clones. kat
      expression vectors, which produce high levels of retroviral vector transcripts
      and retroviral packaging functions, were transfected into 293 cells followed by
      virus harvest 48 hours posttransfection. Viral titers as high as 3.8 proviral
      copies/cell/mL of frozen supernatant in 3T3 cells were obtained, 10- to 50-fold
      greater than transient viral titers reported using 3T3-based retroviral packaging
      lines. Cocultivation of primary human CD8+ T lymphocytes after transient
      transfection of 293 cells with kat plasmids resulted in transduction efficiencies
      of 10% to 40%, 5- to 10-fold greater compared to cocultivation with a high titer
      PA317 producer clone and significantly greater than previously reported results
      for transduction of primary human T lymphocytes with retroviral vectors. Virus
      produced using the kat system was shown to be free of detectable replication
      competent retrovirus by an extended provirus mobilization assay, demonstrating
      that this system is as safe as currently available stable packaging lines. The
      kat virus production system should be of general use for the rapid production of
      high titer viral supernatants, as well as for high-efficiency transduction
      hematopoietic cell types refractory to retroviral transduction.

PMID- 8274752
TI  - Cancer genes and hematopoiesis.

PMID- 8274753
TI  - Expression of platelet-derived growth factor and its receptors by two pre-B acute
      lymphocytic leukemia cell lines.
AB  - Platelet-derived growth factors (PDGF) are potent regulators of cell
      proliferation. The three isoforms of PDGF AA, AB, and BB are encoded by two
      genes: PDGF A and PDGF B. The v-sis oncogene is homologous to the PDGF-B gene. v
      sis can transform cells that express the appropriate PDGF receptors. Two
      different types of receptors, PDGF-alpha and PDGF-beta, also encoded by two
      genes, have been identified. We show that two cell lines. SMS-SB and NALM-6, both
      derived from pre-B-cell acute lymphocytic leukemias, express the PDGF-A chain
      gene, and one of them, SMS-SB, releases PDGF-A chains into the media. The SMS-SB
      cells also express the PDGF-beta receptor, whereas NALM-6 cells express the PDGF
      alpha receptor and bind PDGF. This extends the possible targets for PDGF to the B
      cell lineage lymphocytes.

PMID- 8274754
TI  - Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha
      and anti-GD3 ganglioside monoclonal antibody in patients with metastatic
      melanoma.
AB  - Hemorrhagic tumor necrosis is an inflammatory event that leads to selective
      destruction of malignant tissues, with both potentially toxic and beneficial
      consequences. A pilot clinical trial was undertaken combining tumor necrosis
      factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3
      ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to
      recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to
      activate leukocytes. Eight patients were treated and seven patients had mild
      toxicity. One patient with extensive metastatic melanoma developed tumor lysis
      syndrome within hours after treatment with almost complete necrosis of bulky
      tumors in multiple visceral sites. To our knowledge, this is the first documented
      case of hemorrhagic tumor necrosis in a patient with metastatic cancer in
      multiple visceral sites.

PMID- 8274755
TI  - Protection of murine bone marrow by dexamethasone during cytotoxic chemotherapy.
AB  - Corticosteroids have the ability to suppress the production of growth factors and
      cytokines and are thus implicated in the negative regulation of hematopoiesis. We
      have shown that the corticosteroids, prednisolone and dexamethasone, were able to
      effectively protect progenitor cells in four strains of mice against cell-cycle
      specific antimetabolic chemotherapy agents. The highest levels of protection
      against 5-fluorouracil (FU; 200 mg/kg) were achieved when two or three
      intraperitoneal injections of dexamethasone were administered between -7 and +3
      hours at a dose of 7.5 mg/kg/injection (optimal dose) or by continuous infusion
      between -4 and +20 hours. This protective effect is manifested as an increase in
      the number of high proliferative potential colony-forming cells that survive in
      the bone marrow 3 days after treatment with FU from between 0.5% and 11% to
      between 10% and 34% of normal. The bone marrow progenitors and blood cell numbers
      return to normal from 3 to 5 days and 1 to 2 days earlier, respectively. Less
      dexamethasone than prednisolone is required to give an equivalent protective
      effect, which is consistent with their anti-inflammatory potency. These findings
      are further evidence of the negative regulatory role played by corticosteroids,
      and indicate that the treatment schedules of corticosteroids during cancer
      therapy need to be reexamined to obtain the maximum benefit from their use.

PMID- 8274756
TI  - Circulating erythroid progenitors in polycythemia vera are hypersensitive to
      insulin-like growth factor-1 in vitro: studies in an improved serum-free medium.
AB  - We have investigated the question of erythropoietin (Epo) hypersensitivity versus
      Epo independence as the basis for the endogenous erythroid bursts (EEBs) that
      develop in cultures without added Epo from hematopoietic cells of polycythemia
      vera (PV) patients. Using an improved serum-free (SF) medium containing
      interleukin (IL)-3, but no insulin-like growth factor-1 (IGF-1), and devoid of
      contaminants that influence erythropoiesis, we compared circulating normal and PV
      early erythroid progenitors (BFU-E) with respect to their responses in vitro to
      recombinant human (rHu) Epo. Cultures were seeded with Ficoll-Hypaque density
      separated peripheral blood (PB) mononuclear cells (MNCs), and erythroid bursts,
      together with their component colonies of > or = 50 cells, were scored in situ at
      13 to 16 days of culture. The Epo dose-response curve of BFU-E from PV patients
      was found to be statistically indistinguishable from that of normal subjects.
      This observation provides compelling evidence against the Epo-hypersensitivity
      hypothesis. In the complete SF medium minus Epo, the sensitivity of BFU-E to IGF
      1 was much greater in PV than in normals, the dose-response curve being shifted
      to the left by at least 2 orders of magnitude. These data show that the erythroid
      progenitor cell response in PV is hypersensitive to IGF-1, and independent of
      Epo. The data also emphasize the importance of truly SF medium conditions for
      assessment of progenitor cell sensitivities to recombinant growth factors.
      Depletion of adherent cells totally prevented erythroid burst formation by normal
      circulating progenitors, but did not prevent the hypersensitive response to IGF-1
      of such cells from PV patients. Hence, again unlike its normal counterpart, the
      progenitor cell response in PV appears to be independent of adherent cell
      control.

PMID- 8274757
TI  - Special issue: Neural mechanisms of the mammalian circadian system.

PMID- 8274758
TI  - Photoreceptors regulating circadian behavior: a mouse model.
AB  - Our recent studies have examined circadian photoreception in mice with hereditary
      retinal disorders (rd/rd and rds/rds). Despite the loss of visual function in
      these mice, circadian responses to light remain unaffected. Using c-fos
      expression within the suprachiasmatic nuclei (SCN) as a marker of neural
      activation of the circadian entrainment pathway, we have found identical levels
      of Fos in the SCN of rd/rd and +/+ mice in response to retinal illumination. On
      the basis of action spectrum studies, and measurements of photopigment retinoids
      using high-pressure liquid chromatography, we believe that the photopigment
      mediating circadian responses to light is based upon an opsin, and that 11-cis
      retinaldehyde is the photopigment chromophore. Preliminary measurements of mouse
      rod opsin, blue cone, and green-red cone opsin messenger RNA in retinally
      degenerate mice suggest that none of these opsins is exclusively used to mediate
      circadian responses to light. Collectively, our data suggest that circadian
      photoreception can be maintained by a very small number of rod or cone cells
      without outer segments, or, alternatively, is performed by an unrecognized class
      of photoreceptive cell within the mammalian retina.

PMID- 8274759
TI  - Molecular approach to hypothalamic rhythms: isolation of novel indoleamine
      receptor genes.
AB  - We have utilized polymerase chain reaction with primers corresponding to
      conserved amino acid sequences within membrane-spanning regions of known
      serotonin receptors to identify clones of four putative new indoleamine
      receptors. We have determined complete amino acid sequences of these four
      receptors, which fall into three subfamilies; two of these subfamilies are novel.
      The sites of expression within the brain have been determined for each of the
      genes. Expression in mammalian cells demonstrates that each new protein is a
      receptor for serotonin and that each has a distinct pharmacology when compared to
      known receptors. Two of the new receptors are coupled to cyclic adenosine
      monophosphate, one negatively (Gi) and one positively (Gs). The latter is a
      candidate for the serotonin receptor that mediates phase advances in circadian
      rhythms of the suprachiasmatic nucleus.

PMID- 8274760
TI  - Organization of the primate circadian system.
AB  - The circadian timing system has three principal elements: the retina, the
      intergeniculate leaflet (IGL) of the thalamus, and the suprachiasmatic nucleus
      (SCN). Since the human circadian timing system cannot be studied experimentally,
      we have used another primate, the macaque monkey, to help provide insight into
      the organization of the human circadian system. The retinohypothalamic tract
      (RHT) in the monkey projects to the SCN, the anterior and lateral hypothalamic
      areas, and the retrochiasmatic area in a pattern very similar to that in the rat.
      The monkey SCN has a population of vasoactive intestinal polypeptide-containing
      (VIP+) neurons in a zone that overlaps the RHT termination and the termination of
      neuropeptide Y-containing (NPY+) axons arising in the IGL. This zone is
      surrounded by a population of vasopressin-containing (VP+) neurons. The human SCN
      is similar to that of other mammals with populations of VIP+ and VP+ neurons, but
      it differs in having a large population of neurotensin-containing (NT+) neurons
      that extends over the entire nucleus, and a moderate population of NPY+ neurons
      located centrally in the nucleus in the presumed area of RHT termination. The
      lateral geniculate nucleus in the monkey and human is quite different from that
      in rodents, but contains an area in the pregeniculate nucleus that receives
      bilateral retinal projections in the monkey and is characterized in both the
      monkey and human by a population of NPY+ neurons and a plexus of enkephalin- and
      substance P-containing axons. This nucleus appears homologous to the rodent IGL.

PMID- 8274761
TI  - Electrophysiology of the suprachiasmatic nucleus: synaptic transmission, membrane
      properties, and neuronal synchronization.
AB  - Knowledge of the neuronal membrane properties and synaptic physiology of the
      suprachiasmatic nucleus (SCN) is critical for an understanding of the cellular
      basis of circadian rhythms in mammals. The hypothalamic slice preparations from
      rodents and a combination of electrophysiological techniques (i.e., extracellular
      single- and multiple-unit recording, intracellular recording, and whole-cell
      patch clamp) were used to study (1) the role of excitatory and inhibitory amino
      acids (i.e., glutamate and gamma-aminobutyric acid [GABA] in synaptic
      transmission, (2) the membrane properties of SCN neurons, and (3) the mechanisms
      of neuronal synchronization. Antagonists for N-methyl-D-aspartate (NMDA)
      receptors and non-NMDA receptors blocked excitatory postsynaptic potentials
      (EPSPs) evoked by stimulation of the optic nerve or other sites when SCN cells
      were depolarized or at rest, respectively. Bicuculline blocked inhibitory
      postsynaptic potentials (IPSPs) that were evoked by local stimulation or that
      occurred spontaneously. The IPSP reversal potential was near the Cl- equilibrium
      potential, and was shifted to depolarized levels by raising intracellular [Cl-].
      Thus, glutamate and GABA appear to mediate fast excitatory and inhibitory
      synaptic transmission in the SCN. Some SCN neurons, but not all of them, had low
      threshold Ca2+ spikes and time-dependent inward rectification, thus indicating
      that the electrical properties of SCN neurons are not homogenous. Neurons with a
      firing rate of > 6 Hz had a regular pattern, and neurons with a rate of < 4 Hz
      had an irregular pattern; since both the firing rate and pattern could be
      modified with injected currents, SCN neurons with different firing patterns are
      unlikely to represent distinct classes of cells.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274762
TI  - Neurophysiological analysis of circadian rhythm entrainment.
AB  - We review recent studies in our laboratory that have investigated the neural
      mechanisms underlying photic entrainment of the mammalian circadian system. The
      results from studies of extracellular single-unit recordings and of photic
      induction of Fos-like immunoreactivity (Fos-lir) indicate that excitatory amino
      acid (EAA) transmission, and particularly activation of the N-methyl-D-aspartate
      (NMDA) receptor subtype, is important for conveying photic information to
      suprachiasmatic nucleus (SCN) cells. We have also found that a subregion of the
      SCN still shows Fos-lir after blockade of EAA receptors, and we have evidence
      suggesting that these cells are innervated by a distinct subdivision of the
      retinal projection to the SCN. In addition, we have found that photic responses
      of cells in the intergeniculate leaflet (which projects to the SCN) and of SCN
      cells are modulated by serotonin (5-HT) via a receptor that resembles the 5-HT1A
      subtype.

PMID- 8274763
TI  - Is Fos expression necessary and sufficient to mediate light-induced phase
      advances of the suprachiasmatic circadian oscillator?
AB  - Photic stimulation during the subjective night induces the expression of Fos
      among a discrete population of cells in the suprachiasmatic nuclei (SCN) region
      of the Syrian hamster. Light appears to stimulate Fos expression only when
      administered at circadian times (CTs) at which exposure causes a phase shift.
      Different populations of SCN cells express Fos in response to light pulses that
      result in phase advances versus phase delays, raising the possibility that
      different cell populations in the suprachiasmatic hypothalamus participate in
      light-induced phase advances and delays of the circadian oscillator.
      Microinjection of excitatory amino acid (EAA) antagonists into the region of the
      SCN attenuates light-induced phase advances of the free-running activity rhythm
      and light-induced Fos expression in the hamster SCN. However, injection of N
      methyl-D-aspartate (NMDA) at CT 18, which results in a widespread pattern of Fos
      expression in the hypothalamus that includes the retinorecipient zone of the SCN,
      does not produce phase advances of the circadian oscillator. The results
      demonstrate that both light-induced Fos expression and light-induced phase
      advances are dependent upon EAA neurotransmission within the SCN region. However,
      expression of Fos in the SCN induced by the EAA agonist NMDA is not sufficient to
      cause phase advances of the SCN oscillator.

PMID- 8274764
TI  - Circadian regulation of c-fos expression in the suprachiasmatic pacemaker by
      light.
AB  - The primary objective of this research was to examine expression of the immediate
      early gene c-fos within the suprachiasmatic nucleus (SCN) for evidence of
      circadian regulation by photic stimuli. In vivo and in vitro analyses demonstrate
      that photic signals have an inductive effect on c-fos expression in the SCN, but
      only at critical times when light is capable of phase-shifting circadian rhythms.
      This evidence for correlative relations between the effects of light signals in
      inducing c-fos gene expression in the SCN and modulating the circadian period of
      the SCN pacemaker suggests that immediate-early genes may be components of the
      signal transduction cascade by which light entrains circadian rhythms. In
      addition, dual-immunostaining methods were utilized to examine neurochemical
      identity of SCN cells that exhibit this circadian induction of c-fos expression
      in response to light. Within the ventrolateral SCN, the photic induction of Fos
      expression occurred in neurons expressing gastrin-releasing peptide (GRP), but
      not in those containing vasoactive intestinal polypeptide (VIP). This finding
      suggests that SCN neurons containing GRP may be involved in the transduction of
      photic signals mediating circadian entrainment.

PMID- 8274765
TI  - Melatonin, the pineal gland, and circadian rhythms.
AB  - Amniote circadian organization derives from the interactions of circadian
      oscillators and photoreceptors located in the hypothalamic suprachiasmatic nuclei
      (SCN), the pineal gland, and the eyes. In mammals, circadian organization is
      dominated by the SCN, which serve as "master pacemakers" in the control of a wide
      array of behavioral and physiological rhythms (including locomotion, sleep-wake,
      thermoregulation, cardiovascular function, and many endocrine processes). Among
      the rhythms under SCN control in mammals are the circadian synthesis and
      secretion of the pineal hormone melatonin, which relies on a multisynaptic
      pathway via the sympathetic nervous system to maintain and entrain rhythmicity in
      this hormone. Several studies have indicated that pineal melatonin feeds back on
      SCN rhythmicity to modulate circadian patterns of activity and other processes.
      However, the nature and system-level significance of this feedback are unknown.
      Recently published work indicates that although pinealectomy does not affect rat
      circadian rhythms in light-dark cycles or constant darkness, wheel-running
      activity rhythms are severely disrupted in constant light. These data suggest
      that either (1) pineal feedback regulates the light sensitivity of the SCN,
      and/or (2) it affects coupling among circadian oscillators within the SCN or
      between the SCN and its output. Research in our laboratory is currently
      addressing each of these hypotheses.

PMID- 8274766
TI  - Culture and transplantation of the mammalian circadian pacemaker.
AB  - In transplantation studies using the tau mutation in the golden hamster, it has
      been demonstrated that suprachiasmatic nucleus (SCN) pacemaker cells and
      mechanisms of communication with the host brain are retained even after tissue
      dissociation and maintenance for many weeks in primary cell culture. Brain grafts
      of cultured SCN cells are capable of restoring overt rhythms of locomotor
      activity, and preliminary studies where cells from two tau genotypes are combined
      in a single graft demonstrate that pacemaker cells may communicate with each
      other to produce coherent rhythms with intermediate periods. The opportunity is
      presented, therefore, to study pacemaker-pacemaker communication in circadian
      chimeras produced by SCN transplantation. Immunocytochemical analysis of graft
      host interactions requires the positive identification of host versus donor
      cells. Although grafted blocks of tissue are easily recognized during
      immunocytochemical analysis, implants of dissociated and cultured cells may be
      more diffusely located and are not as readily identified. Unless distinct strain-
      or species-specific markers are available, it is difficult to identify
      connections that may carry timing information to the host organism. We have taken
      an anatomical approach that utilizes cell-labeling techniques for hamster tissue
      along with foreign protein expression in transgenic mice to identify patterns of
      communication among graft and host cells, focusing specifically on SCN-SCN
      communication. The data indicate the usefulness of these transgenes as markers in
      transplantation studies where communication between graft and host is addressed.

PMID- 8274767
TI  - Efferent signals of the suprachiasmatic nucleus.
AB  - It is well established that the mammalian suprachiasmatic nucleus (SCN) is a
      biological pacemaker that entrains the activity of organisms to their environment
      and controls circadian rhythmicity. However, neither the nature of these coupling
      signal or signals from the SCN, nor their target or targets in the brain, are
      well understood. Fiber efferents from the SCN reach nearby hypothalamic regions,
      suggesting a coupling role for neural efferent pathways. The SCN produces
      diffusible signals that reach nearby hypothalamic sites and the cerebrospinal
      fluid, suggesting a role for a diffusible efferent pathway. We consider the
      possibility of redundant coupling signals of the SCN, and review evidence
      suggesting that diffusible elements may be sufficient to sustain locomotor
      rhythmicity in adult animals and to restore locomotor rhythmicity in lesioned
      hamsters bearing SCN grafts. We also provide data for the occurrence of signals
      that synchronize oscillators, regardless of initial phase. The distinct role of
      neural and diffusible SCN coupling signals, and the role of SCN-driven rhythmic
      systems (pineal melatonin rhythms, body temperature), remain to be explored.

PMID- 8274768
TI  - Mutant circadian period as a marker of suprachiasmatic nucleus function.
AB  - Fetal suprachiasmatic nucleus (SCN) tissue transplanted into the third ventricle
      of hamsters bearing complete SCN lesions restores the circadian locomotor rhythm
      with a period that depends exclusively on the genetically determined period of
      the tissue donor. If the host is only partially lesioned and thus retains
      rhythmicity with its own genetically determined period, an implant from an animal
      of a different genotype can induce a second rhythm with a period determined by
      the donor genotype. Both rhythms can be present simultaneously in the record of
      such a "temporal chimera," interacting only superficially (i.e., not at the level
      of the pacemaker). Our data support the interpretation that under such
      circumstances the graft is able to capture part of the locomotor output of the
      circadian system, but does not make functional connections with the host SCN
      pacemaking system.

PMID- 8274769
TI  - Preliminary studies on the immediate phase-shifting effects of light and exercise
      on the human circadian clock.
AB  - The aim of the present research was to determine the magnitude and direction of
      immediate phase shifts of human rhythms following a single exposure to a 3-hr
      pulse of bright light or physical activity. The pulse of light or activity was
      presented under "constant-routine" conditions, and measurements of the resultant
      phase shifts were performed under the same constant-routine conditions on the
      first day following pulse presentation. Four overt rhythms that are strongly
      dependent on circadian timing--namely, the rhythms of plasma cortisol, plasma
      thyroid-stimulating hormone (TSH), plasma melatonin, and body temperature--were
      monitored. The analysis of the TSH profiles indicated that exposure to light at
      about the time of the minimum of body temperature resulted in phase advances
      averaging less than 1 hr in magnitude. Exposure to light approximately 3 hr
      before the time of the minimum of body temperature resulted in phase delays of 1
      2 hr. Preliminary analyses of the melatonin profiles have confirmed these
      observations. Our findings regarding the effects of exercise are still
      inconclusive.

PMID- 8274770
TI  - Nucleotide sequence and properties of the hrmA locus associated with the
      Pseudomonas syringae pv. syringae 61 hrp gene cluster.
AB  - The hrmA locus, isolated from Pseudomonas syringae pv. syringae 61, is essential
      for phenotypic expression of the P. s. pv. syringae 61 hrp cluster in Escherichia
      coli strains and enables bacteria carrying the hrp/hrm gene cluster to elicit the
      hypersensitive response (HR) associated with plant disease resistance. The
      phenotype of P. s. pv syringae 61 hrmA mutants (pathogenicity+, delayed HR) was
      distinct from that of hrp mutants. The locus was localized to a 3.6-kb BamH1
      EcoR1 fragment whose nucleotide sequence was determined. A single open reading
      frame was identified that encodes for a 41,457-Da protein of unknown biochemical
      function. Production of the deduced protein product was confirmed by using T7 RNA
      polymerase-directed expression of the locus and N-terminal sequence analysis of
      the isolated HrmA. The deduced protein product did not exhibit homology with any
      of the characterized avr genes or the hrpN product of Erwinia amylovora.
      Transcription was shown to initiate 37 nucleotides upstream of the translational
      start from an apparent sigma 70 promoter. Two hrp genes were shown to act as
      positive transcriptional factors for hrmA expression. Expression of hrmA in P.
      syringae pv. glycinea race 4 did not exhibit the phenotypic properties of an avr
      gene or HrpN, but suggested that this locus may serve a regulatory function. A
      homolog to hrmA was present in strains of only three of the 23 P. syringae
      pathovars tested.

PMID- 8274771
TI  - A gene encoding a host-specific elicitor protein of Phytophthora parasitica.
AB  - Extracellular elicitor proteins (elicitins) from Phytophthora species induce
      local and distal defense responses specifically in plants of the Solanaceae and
      Cruciferae. Based on elicitin amino acid sequences, elicitin-coding sequences
      from P. parasitica were amplified by the polymerase chain reaction. A genomic
      clone containing a complete elicitin gene, parA1, was isolated and sequenced.
      Elicitin was confirmed to be encoded as a precursor protein containing a 20-amino
      acid signal peptide that is processed before secretion. Bacterial expression of
      the cloned elicitin gene as a translational fusion protein containing glutathione
      S-transferase yielded a biologically active protein capable of inducing a
      hypersensitive response in tobacco, suggesting that fungus-specific
      postranslational modifications of elicitin are not required for its activity.
      Southern blot analysis indicated that elicitin genes occur as a multigene family
      (at least two to 10 copies) in P. parasitica, P. capsici, P. citricola, P.
      citrophthora, P. cryptogea, P. drechsleri, P. megasperma, and P. palmivora. Some
      isolates of P. parasitica that did not produce elicitins still contained elicitin
      coding sequences but did not accumulate elicitin mRNA.

PMID- 8274772
TI  - Recognition of the avirulence gene avrB from Pseudomonas syringae pv. glycinea by
      Arabidopsis thaliana.
AB  - The response of Arabidopsis thaliana land race Columbia to the bacterial pathogen
      Pseudomonas syringae pv. maculicola 4326 harboring cloned avirulence genes avrB
      and avrC from P. syringae pv. glycinea and avrA and avrD from P. syringae pv.
      tomato was examined. Only avrB was recognized by Columbia, as evidenced by
      attenuation of disease symptoms, slower bacterial multiplication in planta, and
      differentially greater induction of mRNA for several defense-related genes. This
      contrasts with two A. thaliana land races where P. s. pv. maculicola strains
      containing avrB were not recognized. These plants showed typical disease
      symptoms, and bacterial multiplication in planta was not reduced in response to
      P. s. pv. maculicola containing avrB. In addition, there was no differential
      induction of defense-related mRNAs in these susceptible land races after
      infiltration with bacteria containing or lacking avrB. These results extend
      previous observations that avirulence genes from pathogens of one host plant can
      be recognized by "nonhost" plants and provide the genetic framework for analysis
      of the plant-specified response to the bacterial avrB gene product in A.
      thaliana.

PMID- 8274773
TI  - Avirulence gene avrRxv from Xanthomonas campestris pv. vesicatoria specifies
      resistance on tomato line Hawaii 7998.
AB  - The molecular and genetic control of the interaction between tomato races of
      Xanthomonas campestris pv. vesicatoria (XcvT) and tomato was studied. Based on
      inoculation phenotype and analysis of in planta bacterial growth, tomato line
      Hawaii 7998 is resistant to XcvT race 1 75-3 but not to XcvT race 2 89-1. Two
      cosmid clones from a genomic library of XcvT race 1 75-3 converted the normally
      virulent race 2 89-1 to avirulence on Hawaii 7998. The two clones contained the
      previously isolated, nonhost avirulence gene avrRxv, and their activity was
      localized to a 2.1-kbp subclone of avrRxv. avrRxv inhibits growth of race 2 89-1
      in the resistant line Hawaii 7998 and an insertional mutation in avrRxv prevents
      this inhibition. In addition, a dramatic increase in electrolyte leakage of
      leaves of Hawaii 7998 occurred after 12-hr postinfiltration with race 2 89-1
      carrying avrRxv. The nucleotide sequence of avrRxv revealed one major open
      reading frame (ORF) that accords well with activity analysis of nested deletions.
      ORF 2-2 encodes a putative protein of 374 amino acids with a molecular weight of
      42.1 kDa and a pI of 10.7. Inheritance of the avrRxv-specific resistance in
      Hawaii 7998 was studied in a total of 587 F2 individuals from crosses between
      Hawaii 7998 and susceptible lines. The inheritance of avrRxv-specific resistance
      in Hawaii 7998 appears to be governed by more than one locus.

PMID- 8274774
TI  - Broad resistance to tobamoviruses is mediated by a modified tobacco mosaic virus
      replicase transgene.
AB  - Tobacco plants made transgenic to express the wild type tobacco mosaic virus
      (TMV) 183-kDa replicase gene were not resistant to TMV. However, transgenic
      plants containing essentially the same sequences, but with an additional
      insertion that would terminate translation in the middle of the 183-kDa gene,
      were highly resistant to systemic infection by TMV and other tobamoviruses. The
      1.4-kbp insertion in the replicase open reading frame (ORF) of the resistant
      plants was shown by DNA sequencing to be an IS10-like transposable element, which
      apparently inserted itself into the TMV sequence at nucleotide 2875 sometime
      during the propagation of this replicase ORF plasmid (pREP21). Because of four
      stop codons, in frame with the TMV replicase ORF on the immediate 5' border of
      the IS insertion, REP21 effectively represents domain 1 (putative methylase
      domain) and a portion of domain 2 (putative helicase domain) of the TMV replicase
      ORF. REP21 Xanthi tobacco plants had a level of resistance to TMV similar to
      other reported transgenic replicase plants. No TMV was detected in upper leaves
      of these plants at 1-mo postinoculation. In addition, REP21 plants were resistant
      to an unusually broad range of tobamoviruses including tomato mosaic virus,
      tobacco mild green mosaic virus, TMV-U5, green tomato atypical mosaic virus, and
      ribgrass mosaic virus. These plants were not resistant to cucumber mosaic
      cucumovirus. The lack of systemic infection by TMV was due to reduced
      multiplication in inoculated leaves rather than complete prevention of
      replication.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274775
TI  - Pathological and molecular characterizations of alfalfa interactions with
      compatible and incompatible bacteria, Xanthomonas campestris pv. alfalfae and
      Pseudomonas syringae pv. pisi.
AB  - We report on the interactions of alfalfa with Xanthomonas campestris pv. alfalfae
      and Pseudomonas syringae pv. pisi. A hypersensitive response was observed when
      leaves were infiltrated with P. s. pv. pisi, which remained strictly limited to
      the injected zone. The compatible interaction with X. c. pv. alfalfae was
      characterized by water-soaking symptoms and the spreading of the bacterium into
      the leaf blade. Analyses of transcript accumulation were conducted with cDNAs
      encoding enzymes involved in phytoalexin synthesis: chalcone synthase (CHS),
      chalcone isomerase (CHI), and isoflavone reductase (IFR). In incompatible
      interactions the maximum accumulation of the CHS, CHI, and IFR transcripts was
      observed 6 hr postinfection. In the compatible interaction, the induction of
      these transcripts was delayed until 25-30 hr postinfection, and the level of
      their accumulation was considerably lower. Extending this molecular analysis to
      the root system showed that the reaction of roots during an incompatible
      interaction was quite comparable to that of leaves. To complete these analyses,
      expression of genes encoding pathogenesis-related (PR) proteins in leaves was
      also analyzed by polymerase chain reaction. High-level accumulation of a 0.8-kb
      transcript encoding a PR protein was observed 6 to 30 hr postinfection in the
      incompatible interaction.

PMID- 8274776
TI  - The persistence of engineered Agrobacterium tumefaciens in agroinfected plants.
AB  - Several plant species, including tomato (Lycopersicon esculentum), Gynura
      aurantiaca, avocado (Persea americana), and grapefruit (Citrus paradisi) grafted
      on Troyer citrange (Poncirus trifoliata x C. sinensis) were "agro-infected" with
      Agrobacterium tumefaciens strain LBA-4404, carrying a mini-Ti plasmid with a
      dimeric cDNA of citrus exocortis viroid (CEVd). Extracts prepared from tissues of
      the agroinfected plants 38-90 days after inoculation were plated on selective
      media and found to contain large amounts of the engineered bacteria. These
      observations suggest the need for more stringent quarantine measures when
      handling A. tumefaciens cells harboring constructs for "agroinoculation" with
      plant viruses or viroids.

PMID- 8274777
TI  - Hair growth evaluation in clinical dermatology.

PMID- 8274778
TI  - Topical iontophoretic drug delivery in vivo: historical development, devices and
      future perspectives.
AB  - Iontophoresis increases penetration of charged substances through the skin under
      a potential gradient. In spite of a century of publication, widespread use of the
      technique for enhancing percutaneous penetration has not yet been made. Knowledge
      of the mechanism and instrumentation increased exponentially in the last decade.
      In vivo iontophoretic devices vary in complexity from household current used in
      the past to a simple battery-and-rheostat type to modern electronic circuit
      devices. Extensive research is still required in the area of material science,
      electronics and skin toxicology to maximize this technique for controlled
      systemic transdermal administration of charged, hydrophilic and large drug
      molecules.

PMID- 8274779
TI  - Polyester but not cotton or wool textiles inhibit hair growth.
AB  - The effect of different types of textile fabrics on hair growth was investigated
      in 40 mongrel dogs divided into 5 groups. An area of 10 x 20 cm on the dog's back
      was shaved; half of this area was covered by a textile patch of 100% polyester
      material in the 1st group, 100% cotton in the 2nd group, 100% wool in the 3rd
      group and a 50%/50% polyester/cotton blend in the 4th group. The remaining half
      of the shaved area in the 4 groups as well as the whole area in the 5th group
      (control) were left uncovered. The textile patch was worn for 2 months. The
      polyester-covered hair grew at a significantly lower rate and density than in the
      uncovered area of the same animal and the controls (p < 0.01). The hair color was
      similar to that of the surrounding uncovered hair. This is in contrast to cotton-
      and wool-covered skin area which showed nonsignificant differences in hair
      density, growth rate and color (p > 0.05) against the uncovered area and
      controls. In the polyester-covered skin, a thinning of the epidermis of the skin
      was noted microscopically with fragmentation and vacuolation of the hair follicle
      pulp. The study has shown that the polyester material generated electrostatic
      potentials, which may have inhibited hair growth, whereas cotton and woolen
      textiles did not. Friction between the polyester textile and the skin generates
      electrostatic charges which are suggested to create an 'electrostatic field' that
      seems to be responsible for the inhibited hair growth.

PMID- 8274780
TI  - Diffuse partial woolly hair.
AB  - We report 4 new cases presenting with the characteristics of a recently described
      pilar dysplasia entitled 'diffuse partial woolly hair'. Two of our cases were
      familial (mother and daughter), while the 2 other were sporadic. Scalp hair of
      all the patients exhibited two hair shaft populations intermingled throughout the
      scalp. The first hair type was straight, normally pigmented and of normal length,
      while the second type was wavy and the shafts were hypopigmented, thinner,
      shorter and easily pluckable. One of our patients presented with a diffuse hair
      thinning due to a progressive loss of wavy hairs. Under reflected light, both
      hair populations displayed alternating dark and bright segments. Scanning
      electron microscopic analysis of straight and wavy hairs revealed comparable
      lesions: torsions, angular kinks, weathering as well as grooved segments
      alternating with the normal ones. These changes were the most severely expressed
      in the shortest and the waviest hairs. Taken together, the clinical and
      microscopic characteristics of this pilar dysplasia justify its introduction as a
      separate entity into the woolly hair group.

PMID- 8274781
TI  - Hermansky-Pudlak syndrome in a Swiss population.
AB  - Tyrosinase-positive albinism, previously diagnosed as Hermansky-Pudlak Syndrome
      (HPS), has been examined in four generations from a village of the canton Valais,
      Switzerland. Homozygotes, obligate heterozygotes and putative heterozygotes in
      this geneology yielded lower than normal membrane-associated thioredoxin
      reductase (TR) activities compared with normal family members and controls. All
      of the homozygotes and 50% of each the obligate and putative heterozygotes showed
      an increase in bleeding time associated with storage-pool-deficient platelets
      lacking dense bodies. The TR activity profile and the platelet-dense body
      deficiency in the Swiss albinos was the same as that in the HPS population from
      Puerto Rico. However, in albinos from Puerto Rico, there is an accumulation of
      ceroid/lipofuscin-like pigment in lysosomal structures causing tissue damage,
      and, upon kidney involvement, this leads to increased urinary dolichol excretion.
      Approximately half of the Puerto Rican HPS cases had clinical evidence of storage
      disease with restrictive lung disease, granulomatous colitis, kidney failure and
      cardiomyopathy. By comparison, the Swiss HPS geneology had a normal life
      expectancy with no significant evidence for ceroid accumulation or urinary
      dolichol excretion. An examination of antioxidant enzymes, catalase, TR and
      glutathione reductase in epidermal suction blisters from Swiss HPS homozygotes
      showed a similar result for catalase and TR levels to the depigmented epidermis
      of patients with vitiligo, except that intracellular TR was found to be calcium
      free in HPS compared with vitiligo. Intracellular glutathione reductase levels
      were highest in HPS. Both the Swiss and Puerto Rican HPS homozygotes and
      heterozygotes have giant melanosomes in skin melanocytes.

PMID- 8274782
TI  - Treatment of eczema with a mixture of triamcinolone acetonide and retinoic acid:
      a double-blind study.
AB  - Dermo-epidermal atrophy is one of the main side effects of long-term treatment
      with topical corticosteroids (TC). Retinoic acid (RA) may prevent and even
      reverse these effects in animals. It has been previously established that topical
      RA (TRA) does not inhibit corticosteroid-induced vasoconstriction in humans, thus
      suggesting that RA, combined with TC, does not interfere with its anti
      inflammatory property. The next step was to test this association in patients
      with inflammatory skin disorders. In this symmetrical double-blind study,
      triamcinolone acetonide (TA) cream 0.1% and a cream containing TA 0.1% plus RA
      0.025% (TARA) were compared in 18 subjects with eczema. No statistical difference
      between both treatments was observed after 1, 2 and 3 weeks, although on the TARA
      treated sides the anti-inflammatory responses were slightly less pronounced.
      Subjective irritation was significantly more frequent in TARA-treated side (3/17,
      p = 0.05) but did not lead to interruption of the treatment. This indicates that
      addition of RA 0.025% to a medium-range potency topical steroid does not abrogate
      the anti-inflammatory property of the latter and that the association can be
      tolerated by inflamed skin.

PMID- 8274783
TI  - Fluconazole-induced toxic epidermal necrolysis in a patient with human
      immunodeficiency virus infection.
AB  - Patients with human immunodeficiency virus (HIV) infection are prone to severe
      drug reactions, mainly from sulfonamides. We report the case of a 33-year-old
      male patient with HIV infection (group IV C-2 of CDC staging system) that
      developed a toxic epidermal necrolysis (TEN) affecting more than 70% of the body
      surface area and severe mucosal involvement after starting fluconazole for a
      recurrent oral thrush with dysphagia. This is to our knowledge the first reported
      case of TEN due to fluconazole.

PMID- 8274784
TI  - Spindle cell carcinoma arising in a port-wine stain.
AB  - We report a 75-year-old man with a port-wine stain (PWS) in whom spindle cell
      carcinoma (SCC) arose within a hemangiomatous area. Although reports on basal
      call carcinoma in association with a PWS exist, no literature is available about
      the development of an SCC within a PWS.

PMID- 8274785
TI  - Mycosis fungoides and eruptive epidermoid cysts: a unique response of follicular
      and eccrine structures.
AB  - A case of a patient who developed simultaneously mycosis fungoides (MF) and
      multiple, tiny eruptive cutaneous cysts on the face, neck and upper part of the
      trunk is reported. Histologically and immunohistochemically MF infiltrate was
      recognized not only in the upper part of the dermis and in the epidermis but also
      around and within the walls of cystic lesions. Furthermore, the eccrine
      structures were also involved by MF infiltrate. We emphasize that MF infiltrate
      can affect the follicular and eccrine structures inducing the formation of
      keratinous cysts. The clinical appearance of the facial lesions may be confused
      with Favre-Racouchot disease.

PMID- 8274786
TI  - 'Nose sign' in dermatology.

PMID- 8274787
TI  - Hiccup--a side-effect of pulse therapy.

PMID- 8274788
TI  - Interferon-induced psoriasis in a patient with chronic hepatitis C.

PMID- 8274789
TI  - Pulse of methylprednisolone in alopecia areata.
AB  - In an attempt to stop the evolution of recent-onset severe alopecia areata (AA),
      we tested pulse corticotherapy on 9 patients. Acceptance into the study was based
      on the following criteria: recent-onset AA (< 1 year), AA in an active state,
      bald surface > 30% of the scalp, no contraindication to pulse corticotherapy.
      Each patient was given 250 mg i.v. of methylprednisolone twice a day on 3
      successive days. In 8 patients the course of the ongoing episode of AA was
      stopped. At the 6-month follow-up, a regrowth on 80-100% of the bald surface was
      observed in 6 patients. One patient did not respond to treatment, and 2 had less
      than 50% of regrowth. This open study suggests that pulse corticotherapy: (1) can
      stop the course of severe AA in an active state, (2) is well tolerated without
      major side effects and (3) does not permit a stable control of AA of more than 1
      year duration. This treatment seems to be indicated for severe AA of recent
      onset.

PMID- 8274790
TI  - Serious long-term complication following silicone injection of the face.
AB  - Following liquid silicone injections of the face, a 48-year-old patient developed
      a more and more serious painful swelling during a period of 3 years. The
      diagnosis of a local long-term complication after silicone injection could be
      established. There were no signs of a systemic complication.

PMID- 8274791
TI  - Pigmentation following long-term bismuth therapy for pneumatosis cystoides
      intestinalis.
AB  - In the recent literature, only a few reports deal with generalized pigmentation
      caused by bismuth treatment. We report a patient developing generalized
      pigmentation of the skin and mucous membranes without further signs of chronic
      bismuth poisoning following long-term administration of bismuth for pneumatosis
      cystoides intestinalis. Bismuth deposits were documented in a skin biopsy.

PMID- 8274792
TI  - Disulfite-induced acute intermittent urticaria with vasculitis.
AB  - Recognition of sulfite sensitivity by the practicing dermatologist has become
      increasingly important. A wide spectrum of anaphylactoid reactions can occur
      after ingestion of sulfite additives in foods and medications. We report the case
      of a 47-year-old man with severe acute intermittent urticaria. A placebo
      controlled oral challenge test with 50 mg sodium disulfite resulted in an acute
      urticaria attack. A biopsy taken 5 h after the appearance of the urticaria
      demonstrated a leukocytoclastic vasculitis with eosinophilia. Avoiding foods and
      drugs containing sulfites is often difficult due to its widespread use.
      Therefore, the patient should be equipped with a medical emergency kit.

PMID- 8274793
TI  - Collision dermatosis: angiolymphoid hyperplasia with eosinophilia developing
      within a congenital port wine nevus.
AB  - This is the report on a 22-year-old man suffering since birth from a port wine
      nevus at his left shoulder, which at the age of 21 showed slight thickening in
      the central area of the lesion. Histology revealed typical features of nevus
      flammeus at the border zone and in the newly developing central area
      proliferation of dilated vessels with prominent endothelial walls surrounded by
      dense lymphoid cell infiltrates containing many eosinophils and lymph-follicle
      like structures in the mid and deep dermis, compatible with angiolymphoid
      hyperplasia with eosinophilia (ALHE). This is the first report of ALHE occurring
      in a congenital port wine nevus indicating microenvironmental importance for
      vascular reactive or neoplastic proliferations. The relationship to Kimura's
      disease will be discussed.

PMID- 8274794
TI  - Pili trianguli et canaliculi: a distinctive hair shaft defect leading to
      uncombable hair.
AB  - Uncombable hair syndrome refers to a clinical disorder characterized by scalp
      hairs arranged in bundles in all directions that resist to brush and comb.
      Several entities may lead to spun-glass hair. As a rule the syndrome becomes
      obvious during the first years of life. The hair is normal in quantity, and
      increased fragility is not a common feature. The hair is often dry with silvery
      blond color. Under the light microscope the hairs may appear normal. Scanning
      electron microscopy shows a characteristic triangular, kidney- or heat-shaped
      diameter with typical longitudinal canalicular deformation. We present a 9-year
      old girl with the typical clinical features of pili trianguli et canaliculi.
      Investigation by scanning electron microscopy confirmed the diagnosis. In
      addition the girl had enamel defects of the teeth and nail abnormalities that
      classify for a subtype of ectodermal dysplasia.

PMID- 8274795
TI  - Mycobacterium chelonae infection of lymph nodes in an HIV-infected patient.
AB  - A case of a 28-year-old African HIV-1 positive patient is presented. After an
      abscess following an intragluteal injection in Africa the patient developed an
      enlargement of the inguinal lymph nodes. Mycobacterium chelonae was isolated from
      the enlarged lymph nodes.

PMID- 8274796
TI  - Chronic cutaneous infection caused by Mycobacterium gordonae.
AB  - We report on a patient with a chronic nodular cutaneous infection histologically
      presenting with tuberculoid granulomas and growing Mycobacterium gordonae in
      culture from a biopsy. The lesions were treated surgically. M. gordonae is a
      potentially pathogenic environmental mycobacterium only rarely causing skin
      infections.

PMID- 8274797
TI  - The incidence of Sweet's syndrome in Geneva. A retrospective study of 29 cases.
AB  - Over a 12-year period (1979-1991), 29 cases of Sweet's syndrome (SS) were
      detected in the area of Geneva; 24 patients (82%) could be contacted for follow
      up. The majority of SS occurred between 1979 and 1986, then from 1991 on. The
      annual distribution and especially the absence of cases during 4 years suggest an
      environmental or even infectious factor in SS. Only 4 cases had an underlying
      disease (ulcerative colitis, polycythemia, lymphoma, sarcoidosis) whereas in the
      other, a long-term follow-up, including iterative hematological evaluation, did
      not reveal any underlying condition. Twelve patients were treated by colchicine,
      9 by potassium iodide and 5 by prednisone; in 3 patients remission was
      spontaneous. Nine patients (28%) relapsed; there was no relationship between the
      type of drugs used and the frequency of relapses.

PMID- 8274798
TI  - Bullous systemic lupus erythematosus. Report of a case with lupus erythematosus
      cells in the dermis.
AB  - A 20-year-old black patient with bullous systemic lupus erythematosus developed
      papular and vesicular lesions on the extensor surfaces of the extremities.
      Histologically, subepidermal blisters and papillary neutrophilic abscesses with a
      striking number of lupus erythematosus cells were observed. No circulating anti
      basal-membrane-zone antibodies were found. By Western immunoblotting, the
      patient's serum showed no reactivity against epidermal or dermal extracts.

PMID- 8274799
TI  - Keratosis extremitatum (Greither's disease): clinical features, histology,
      ultrastructure.
AB  - Keratosis palmoplantaris progrediens et transgrediens (Greither's disease) was
      first described by Greither in 1952. The inheritance pattern is autosomal
      dominant with variable expression. The clinical manifestation is characterized by
      diffuse palmoplantar keratoderma associated with hyperhidrosis and progressive
      extension of keratoderma to the dorsum of the hands and feet. In addition,
      hyperkeratotic plaques may occur on the elbows and knees. We describe a 44-year
      old patient with typical features of Greither's disease. Immunohistologic and
      ultrastructural investigations are presented.

PMID- 8274800
TI  - Superficial granulomatous pyoderma.
AB  - We report the case of a 66-year-old man presenting 2 chronic, slowly expanding
      skin lesions having clinical and histopathological characteristics of superficial
      granulomatous pyoderma. Sulfone treatment induced healing with scar formation.

PMID- 8274801
TI  - Relationship between blood pressure and smooth muscle tone in aortae of
      hypertensive rats: roles of [Ca2+].
AB  - Spontaneously developed tension (active tone) and intracellular Ca2+ level of
      aortae from spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP),
      malignant SHRSP (M-SHRSP) and control Wistar Kyoto rats (WKY) were compared.
      Systolic blood pressure of WKY, SHR, SHRSP and M-SHRSP was 130 mmHg, 200 mmHg,
      250 mmHg and 260 mmHg, respectively. Preparations from all strains of
      spontaneously hypertensive rats exhibited active tone which was abolished by the
      removal of extracellular Ca2+ or by the application of verapamil. The active tone
      was greater in the order of aortae from SHR < SHRSP < M-SHRSP. Intracellular Ca2+
      level measured by Fura-2 method decreased by the removal of extracellular Ca2+.
      The degree of the decrease was greater as the blood pressure of the rats
      increased, indicating the greater elevation of intracellular Ca2+ level in the
      pressure of extracellular Ca2+. A correlation was obtained between the active
      tone, intracellular Ca2+ level and blood pressure. Thus, it was demonstrated that
      the development of the active tone is brought about by the changes in Ca2+ influx
      of smooth muscle cell membrane and the degree of the change is positively related
      to the degree of hypertension.

PMID- 8274802
TI  - [Studies on interdigestive intestinal motility of the orthotopic allotransplanted
      canine small bowel].
AB  - We evaluated interdigestive motor patterns in the allotransplanted small bowel,
      in comparison with orthotropic allotransplanted canine jejunoileum and
      orthotropicaly autotransplanted canine jejunoileum or intact ones by using strain
      gage force transducers which were sewn to the serosal surfaces of the duodenum,
      jejunum and ileum. Interdigestive intestinal motility of each conscious dogs was
      recorded at 2 weeks, 4 weeks and 8 weeks after each operation. 1. No significant
      differences were recognized on the mean durations of Interdigestive migrating
      contractions (IMC) of the duodenum among three groups. 2. Interdigestive
      migrating contractions (IMC) appeared at the autotransplanted jejunoileum with
      shorter duration than duodenum, and lacked of coordination between the intact
      duodenum and the transplanted jejunoileum for at least 8 weeks after the
      operation. 3. IMC also appeared at the allotransplanted jejunoileum with shorter
      duration than duodenum and lacked of coordination between the intact duodenum and
      the transplanted jejunoileum for at least 8 weeks after the operation. These
      characteristic motor patterns were similar to those of autotransplanted dogs.
      These observations suggest that intrinsic nervous system, believed to be
      important for initiation of the IMC of small bowel, were preserved even in the
      allotransplanted small bowel. Thereafter, effective immunosuppression must allow
      small bowel allotransplantation to become clinical reality.

PMID- 8274803
TI  - Anterior occipital cervical reconstruction with a free vascularized
      osteocutaneous graft: a case report.
AB  - Free vascularized osteocutaneous bone grafts are an unusual but effective method
      to reconstruct complex and extensive defects of skin and bone of the extremities
      due to trauma, tumor, or infections. Many recent publications support their
      utility in these situations. In distinction, little literature exists to document
      the use of free vascularized osteocutaneous flaps in the spine. This is likely
      due to the infrequent occurrence of concomitant skin and osseous defects that are
      not manageable by routine spinal and plastic surgical approaches. We recently
      managed a particularly challenging patient in whom six prior operations--three
      anterior and three posterior--to decompress and stabilize the occipital-cervical
      junction had failed. We used a free vascularized distal radius osteocutaneous
      flap for three purposes: to provide the patient with an optimal chance to obtain
      an extensive and critically important anterior occipital-cervical arthrodesis, to
      supply a stable soft tissue envelope for protection of a tenuous dural repair,
      and to reconstruct an atrophic and scarred posterior pharyngeal wall. We are
      unaware of any report to date that documents the use of a graft of this type in
      the spine. We wrote this brief article to document the indications for this
      operation, to illustrate the problems we encountered in this difficult
      reconstructive situation, and to report on the progress of our patient to date.

PMID- 8274804
TI  - Cotrel-Dubousset hook and screw combination for spine fractures.
AB  - A review of 14 patients treated for spinal fracture using lumbar pedicle screw
      and thoracic pediculotransverse claw "hybrid" Cotrel-Dubousset fixation was
      performed. Pedicle screw fixation was used one level below the most inferiorly
      injured vertebrae. Pediculotransverse claw constructs were used for thoracic
      level fixation three segments above the superior injured vertebrae. Fractures
      were classified as burst (n = 9), burst dislocation (n = 3), and thoracic facet
      dislocation (n = 2). Complications included one patient who increased his
      kyphosis postoperatively before stabilizing at 3 months and one patient with a
      single screw breakage noted at 1 year. Both patients are asymptomatic. Early
      results demonstrate that this hybrid pedicle screw and pediculotransverse claw
      fixation is a satisfactory alternative to other posterior distraction methods.
      The use of the claw fixation superiorly allows for safe instrumentation in the
      thoracic spine, where pedicle screw placement is hazardous or may not be possible
      due to the small pedicle diameter.

PMID- 8274805
TI  - Magnetic resonance imaging findings of lumbar spine in the young: correlation
      with leisure time physical activity, spinal mobility, and trunk muscle strength
      in 15-year-old pupils with or without low-back pain.
AB  - From a population of 1,503 schoolchildren, 38 15-year-old children reporting
      recurrent or continuous low-back pain and 38 asymptomatic controls (34 boys and
      42 girls) matched for age, sex, and school class were selected for tests of
      spinal mobility and trunk muscle strength, and for a magnetic resonance imaging
      (MRI) study of the lumbar spine. In addition, the subjects were asked about
      leisure time physical activities in an interview preceding the measurements.
      Spinal muscular atrophy was the only finding that was more common among
      physically inactive subjects (p = 0.005). Moreover, increased occurrence of disk
      degeneration (DD) was observed in the low-activity group. However, the difference
      was not significant. Neither Scheuermann-type changes nor DD were related to
      spinal mobility or trunk muscle strength. Children with disk protrusion were, on
      the average, taller (p = 0.044), and their lumbar flexion measured by flexicurve
      was decreased (p = 0.043). Our results strengthen further the evidence that MRI
      is a sensitive measure and that imaging findings must be interpreted carefully
      with respect to pain and physical impairment of the lumbar spine. Furthermore, no
      clear evidence of the association between physical activity and early DD could be
      found.

PMID- 8274806
TI  - Jefferson fractures: the role of magnification artifact in assessing transverse
      ligament integrity.
AB  - Thirty-five consecutive odontoid views were taken using a standardized technique.
      A 10-mm radiographic marker was positioned lateral to the tip of the C-1
      transverse process. Data from three independent readers showed an 18%
      magnification error inherent to anteroposterior open-mouth odontoid radiographs.
      Integrity of the transverse ligament after Jefferson fractures has been inferred
      from the separation of the lateral masses measured on the odontoid view. Spence's
      anatomic study showed that lateral mass separation of > 6.9 mm implied rupture,
      but radiograph magnification was not taken into account. Transverse ligament
      rupture should not be inferred with lateral mass separation of < 8.1 mm.

PMID- 8274807
TI  - Odontoid fractures in the elderly.
AB  - A review of 35 patients > 60 years of age with odontoid fractures showed that a
      type II injury (Anderson and D'Alonso) was the most common fracture pattern (82%
      of cases). On the basis of mechanism of injury and sex incidence, we deduced that
      osteopenia is a contributory factor in the occurrence of odontoid fractures. A
      fall in a domestic setting was the cause in 53%. The peg was posteriorly
      displaced in 88% of type II fractures, and primary union occurred in 23%. The
      incidence of concomitant spinal cord injury with type II fractures was higher in
      older patients than it was in those < 60 years of age. The outcome for these
      patients was largely determined by their neurological status at presentation.
      Myelopathy as a late complication of nonunion was not observed in nine patients
      with an average follow-up of 21 months. The data suggest that vigorous attempts
      to secure both primary union and a sound arthrodesis for non-union are
      questionable in the elderly except in unusual circumstances.

PMID- 8274808
TI  - Micturitional disturbance in radiation myelopathy.
AB  - Detailed micturitional histories and urodynamic studies were performed in five
      patients with radiation myelopathy. All patients had micturitional symptoms that
      were irritative in five and obstructive in four, and four had urinary
      incontinence. Urodynamic studies showed that three patients had residual urine of
      158 ml on average. Cystometry showed that four patients had detrusor
      hyperreflexia and one had low compliance cystometrogram. External sphincter
      electromyography showed that four patients had detrusor-sphincter dyssynergia.
      These results indicated that micturitional disturbance seemed to be common and
      severe in storage as well as evacuation function. The main responsible sites of
      lesions seemed to be supranuclear parasympathetic and somatic nervous systems
      regulating the lower urinary tract. Two of three patients who underwent
      combination of steroid pulse therapy and hyperbaric oxygen therapy experienced
      improvement of micturitional disturbance and other neurological deficits.

PMID- 8274809
TI  - Defects of pars interarticularis in athletes: a protocol for nonoperative
      treatment.
AB  - The purpose of this study was to report the results of a specific treatment
      protocol for athletes with spondylolysis or spondylolisthesis of the lumbar
      spine. A retrospective study with recent follow-up was performed on 82 patients
      treated with restriction of activity, bracing, and physical therapy. All of the
      patients were involved in sports at first onset of symptoms. Sixty-six patients
      were boys and 16 were girls. Activities involving repetitive hyperextension
      and/or extension rotation of the lumbar spine were described as painful in 98% of
      the patients. Of the 62 patients with spondylolysis, 53 (85%) had an L5 defect
      and nine (15%) an L4 defect (90% of these 62 patients' defects were located in
      the most caudad mobile vertebra). Thirty-seven patients had bilateral pars
      defects, and 25 had unilateral defects. Eight patients had normal roentgenograms,
      but these eight had abnormal bone scans. Nine patients with spondylolysis
      underwent posterolateral fusion. Average follow-up was 4.2 years. Fifty-two (84%)
      had excellent results, eight had good results, and two had fair results. Twenty
      patients had a spondylolisthesis: 12 were grade I, six were grade II, and two
      were grade III. Twelve patients (60%) required surgery; 9 had excellent results,
      one had good results, one had a fair result, and one had a poor result. Pars
      defects must be suspected in the differential of low back pain in young athletes.
      Oblique radiographs are frequently diagnostic; however, if the history and
      examination are suggestive despite normal plain films, a bone scan should be
      obtained. Nonoperative management of pars defects is frequently
      successful.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8274810
TI  - Toward the elimination of homologous blood use in elective lumbar spine surgery.
AB  - Two hundred twenty-four consecutive patients underwent elective posterior lumbar
      spinal surgery over a 3 1/2-year span at the University of Miami/Jackson Memorial
      Medical Center. Patients ranged in age from 17 to 87 years, and 58% were male.
      Fifty-eight patients underwent revision surgery, and 65 patients required
      fusions, including 35 necessitating internal fixation. One hundred seventy-four
      patients (78%) were requested to participate in a preoperatively donated
      autologous blood (PDAB) program. Six of these patients were excluded from
      participation, and 168 patients banked 425 U of autologous blood. Eighty percent
      of the patients participating in the PDAB program received some or all of their
      donated blood. Intraoperative blood salvage was used in 37% of cases. Seven
      patients received homologous blood: four in addition to salvaged and donated
      blood, two that were unable to donate blood due to positive hepatitis B serology,
      and one erroneously. The combined use of PDAB and intraoperative salvage program
      allowed autologous blood replacement to meet the total transfusion requirements
      of 96% of the patients who predeposited blood, including 94% of those undergoing
      spinal fusions. Autologous blood comprised 99% of the total blood replacement
      used in this series, and 95% of the patients requiring blood transfusions
      received only autologous blood. Establishment of a protocol judiciously using
      PDAB in conjunction with intraoperative blood salvage can result in virtual
      elimination of the need for homologous blood transfusion in elective lumbar spine
      surgery.

PMID- 8274811
TI  - Evaluation of cervical diskography in pain origin and provocation.
AB  - The purpose of this article is to analyze the role of cervical diskography as a
      diagnostic method via reproduced pain. A nonionic contrast medium (Iohexol) that
      does not harm normal tissue was used in this series to prevent false-positive
      provocative pain. One hundred forty-four patients (128 with cervical spondylotic
      myelopathy, eight with cervical spondylotic radiculopathy, and eight with
      cervical spondylotic amyotrophy) were studied. Among 72 patients in the
      symptomatic neck pain group who complained of neck pain before diskography, 65%
      showed reproduced pain. However, in the control group (neurologic symptoms only)
      50% of the patients complained of provocative neck pain during dye injection.
      These results demonstrated that this provocation technique appeared unreliable
      for diagnosing symptomatic disk levels.

PMID- 8274812
TI  - Thermography as a diagnostic aid in sciatica.
AB  - Thermography has been proposed as a diagnostic aid in patients with sciatica.
      Supporters of thermography state that: (a) normal patients have normal
      thermograms of their lower extremities, and (b) abnormal patients (with disk
      ruptures causing sciatica) have abnormal thermograms. To test these two
      hypotheses, 56 patients with clinically documented acute sciatica, with a
      supporting diagnostic study [computed tomography (CT), CT/myelography, and/or
      magnetic resonance imaging] showing a ruptured disk, had presurgical thermograms.
      One year after surgical intervention, they had to have had a documented success
      to surgical treatment intervention to stay in the study. These 56 patients were
      then matched with 56 control (normal) patients who had electronic thermograms.
      The 112 thermograms were then interpreted blindly by two thermographers. The
      sensitivity and specificity of thermography as a diagnostic aid in sciatica were
      statistically analyzed. The sensitivity of thermography (its ability to be
      positive when sciatica was clinically obvious) was 60% and 50% for the two
      thermographic readers. The specificity of thermography (its ability to be
      negative in asymptomatic patients) was 45% and 48% for the two thermographers.
      Our conclusions are no different than those published in 1985: thermography is
      not useful as a diagnostic aid in sciatica.

PMID- 8274813
TI  - The surgical management of ossification of the posterior longitudinal ligament in
      51 patients.
AB  - Ossification of the posterior longitudinal ligament (OPLL) in the cervical spine
      warrants unique clinical, radiographic, and surgical management. OPLL patients
      presenting with severe myelopathy require full assessment with both magnetic
      resonance imaging (MRI) and computed tomography-based (noncontrast CT, myelo-CT,
      three-dimensional CT) examinations to document the full extent of their disease.
      Whether better surgical outcomes are attained after anterior resection
      (diskectomy/corpectomy), rather than posterior decompression
      (laminectomy/laminoplasty) of OPLL remains controversial. However, our recent
      experience with 51 OPLL patients indicates superior results after anterior (41
      patients) versus posterior (10 patients) surgery. Continuous intraoperative
      somatosensory evoked potential (SSEP) monitoring also appears to limit operative
      morbidity.

PMID- 8274814
TI  - Cervical intramedullary hemorrhage as a result of anticoagulant therapy.

PMID- 8274815
TI  - Drugs of choice in pregnancy: primary prevention of birth defects.

PMID- 8274816
TI  - An international collaborative study of the epidemiology of esophageal atresia or
      stenosis.
AB  - Epidemiologic data were analyzed for a total of 2,693 infants with esophageal
      atresia registered in nine congenital malformation registries around the world.
      The average recorded prevalence at birth was 2.6 per 10,000 births, with a
      significant variability among programs--and sometimes within a program--and a
      maximum prevalence of above 3 per 10,000 births. Clusters of infants with
      esophageal atresia were observed but may be random. An increasing rate was seen
      during the period 1965 to 1975 (Norway, South America, Sweden). The type of
      esophageal atresia was specified in only 439 cases, but no major differences were
      seen in the epidemiologic characteristics of infants with the most common type
      (distal fistula) and infants with other types. There was an excess of low birth
      weight and preterm birth, and infants with esophageal atresia had a birth weight
      500 to 1,000 g less than normal infants in each gestational week. There was an
      excess of twins, apparently mainly or exclusively due to monozygotic twinning,
      but in only two pairs did both twins have esophageal atresia. There was no effect
      seen of maternal age, but low parity, irrespective of maternal age, was
      associated with an increased risk for esophageal atresia. Infant survival varied
      among programs and depended heavily on associated malformations. Among 1,107 sibs
      born before the proband and 385 born after the proband, only 25 (1.7%) had a
      serious malformation; three had esophageal atresia. In 57.3% of the infants with
      esophageal atresia, no other malformations were present, in 36.4% other major
      malformations were recorded, and in 6.3% there were chromosomal anomalies. The
      malformations present associated with esophageal atresia were analyzed: a large
      proportion entered the constellation sometimes called "caudal mesoderm spectrum
      of malformations": VATER, Potter, and caudal regression sequences.

PMID- 8274817
TI  - Decreased teratogen susceptibility in mouse fetuses obtained from delayed mating.
AB  - We examined whether the susceptibility of fetuses to a teratogen differs between
      fetuses from delayed mating and those from normal mating. Mitomycin-C (MMC; 2.5
      mg/kg or 5.0 mg/kg) was administered to pregnant mice intraperitoneally on day 10
      of gestation after either normal or delayed mating (6 h). The incidence of MMC
      induced malformations in fetuses from delayed mating was significantly lower than
      in those from the normal mating group when the treatment time was adjusted to be
      at the same critical period according to the "catch-up" phenomenon of
      developmental progression in the delayed mating group.

PMID- 8274818
TI  - Pharmacokinetics of cocaine in pregnant and nonpregnant rhesus monkeys.
AB  - To determine pharmacokinetic parameters for cocaine in rhesus monkey plasma,
      samples were taken over several hours after i.m. administration of cocaine plus a
      tritiated cocaine tracer. Cocaine and its metabolites, benzoylecgonine and
      norcocaine, were isolated via HPLC and quantitated using liquid scintillation
      spectrometry. Pregnant subjects were dosed with cocaine at 0.3 (n = 3) or 1.0 (n
      = 3) mg/kg, whereas nonpregnant female subjects were dosed with 1.0 mg/kg (n =
      3). For the pregnant subjects, pharmacokinetic studies were conducted on about
      gestational day 125 and areas under the concentration versus time curve (AUCs,
      ng/mL x h) were 64 +/- 26 (+/- SEM) and 143 +/- 12; half-lives (t1/2s, h) were
      1.9 +/- 0.6 and 1.1 +/- 0.1 after 0.3 and 1.0 mg/kg i.m., respectively. For
      nonpregnant subjects dosed acutely with 1.0 mg/kg, the AUC was 262 +/- 63 and the
      t1/2 was 1.4 +/- 0.3. There appear to be few differences in the pharmacokinetic
      parameters of cocaine and benzoylecgonine between pregnant and nonpregnant
      monkeys in this study.

PMID- 8274819
TI  - Differences in the patterns of phenytoin-induced malformations following
      stiripentol coadministration in three inbred mouse strains.
AB  - Differences in the patterns of congenital malformations observed in three inbred
      mouse strains (SWV, LM/Bc, and C57BL/6J) were compared following exposure to
      phenytoin monotherapy and a polytherapeutic regimen of phenytoin and stiripentol.
      Treatment groups containing no fewer than 10 dams were chronically exposed to the
      test compound(s) prior to and throughout gestation. The pattern of fetal defects
      observed included abnormalities of the neural, cardiac, urogenital, and skeletal
      systems. The coadministration of the cytochrome P-450-inhibiting antiepileptic
      drug stiripentol significantly reduced the incidence of fetal malformations in
      all three strains, primarily by reducing phenytoin's deleterious effects on
      congenital abnormalities related directly to fetal growth and development. In the
      SWV fetuses, there were significantly more soft tissue defects (neural and renal)
      than were evident in the LM/Bc fetuses. Overall, the C57BL/6J fetuses were the
      most sensitive to the induction of skeletal defects, with a preponderance of
      defects in the ossification of the craniofacial bones. It is hypothesized that
      the reduction in fetal defects was the result of limiting the biotransformation
      of phenytoin to highly teratogenic oxidative metabolites, which interfere with
      normal fetal growth.

PMID- 8274820
TI  - Caffeine exposure in utero increases the incidence of apnea in adult rats.
AB  - Caffeine abuse during pregnancy may be a factor in the development of long-term
      breathing abnormalities. Therefore, the objective of the present study was to
      monitor adult breathing patterns after in utero exposure to caffeine. This was
      done by isolating episodes of apnea of more than 6-s duration from the breathing
      data as obtained by the Cotwatch breathing monitors adapted for rat use. The
      breathing record obtained over 6 consecutive days was expressed as daily weighted
      apnea-hypopnea density (WAHD) values. It was shown that administration of
      caffeine in moderate (30 mg/kg daily) or high (60 mg/kg daily) doses throughout
      gestation resulted in a significant dose-dependent increase in the WAHD value.
      The experimental offspring were significantly growth retarded in utero and their
      subsequent growth rates were also affected. The caffeine-exposed pups grew more
      slowly with growth plateauing at the same age, resulting in smaller adults. A
      link was suggested between infants with apnea of prematurity, when occurring
      after the first week, and an increased risk for later apnea and sudden infant
      death syndrome.

PMID- 8274821
TI  - Effect of testosterone on diethylstilbestrol toxicity and comparison to a
      recovery study in the rat epididymis and vas deferens.
AB  - Effects of diethylstilbestrol (DES) treatment (30 daily i.m. injections) in
      reproductive function in the male rat were investigated. These functions were
      evaluated with sperm counts, motility, fertility, morphology, serum testosterone,
      and a number of biochemical tests in rat epididymis and vasa deferentia. DES
      treatment resulted in a 15% loss of body weight and a 60 to 90% loss of weight of
      testes, epididymis, and vas deferens. Sperm parameters and fertility were reduced
      to nil by DES treatment. Likewise, the majority of the biochemical measures were
      severely depressed by the DES treatment. In general, the measured parameters were
      less affected or recovered with either testosterone cotreatment or 60 days of
      recovery, showing the role of androgen in maintaining functional integrity and
      metabolism. However, sperm parameters and fertility did not recover with
      testosterone cotreatment, which differs from withdrawal of treatment.

PMID- 8274822
TI  - Synergistic embryotoxicity of combination pyrimethamine and folic acid in rats.
AB  - The increased embryotoxicity of pyrimethamine (PYM) with concomitant oral dosing
      of folic acid (FA) was examined in rats. The preventive effects of folinic acid
      (FNA) on PYM embryotoxicity were also examined. Six groups were constructed: PYM
      I (PYM 1.2 mg/kg/day), FA (FA 50 mg/kg/day), PYM I+FA (1.2 and 50 mg/kg/day,
      respectively), PYM II (2.7 mg/kg/day), PYM II+FNA (2.7 and 12 mg/kg/day,
      respectively), and a vehicle control group. The agents were administered for 11
      days from day 7 throughout 17 of gestation. PYM and FA were administered by
      gavage and FNA was administered intraperitoneally. Visceral and skeletal
      malformations were observed in the fetuses of both PYM I+FA and PYM II groups;
      these included dilatation of the lateral ventricle and fused ribs. No malformed
      fetuses were observed in the fetuses of the other four groups. External
      malformations were observed only in the fetuses of PYM II groups; these included
      cleft palate, cleft lips, and brachygnathia, among others. These results show
      that the concomitant gavage dosing of FA augments PYM embryotoxicity. The
      preventive effects of FNA were also confirmed.

PMID- 8274823
TI  - Autometallographic detection of mercury in testicular tissue of an infertile man
      exposed to mercury vapor.
AB  - A 25-year-old male patient presented with unexplained infertility. Semen analysis
      showed azoospermia or severe oligoasthenoteratospermia with elevated serum FSH.
      The history revealed that he had been employed in a chemical factory for 5 years
      working with chloralkali-electrophoresis. Mercury concentrations in hair, blood,
      and urine samples were considerably above levels of unexposed controls. Bilateral
      testicular biopsies revealed marked interstitial lymphatic infiltration. About
      33% of the tubules analyzed showed a Sertoli-cell-only (SCO) syndrome and tubular
      atrophy. Fewer than 4% of tubules showed qualitatively intact spermatogenesis.
      Autometallographic (AMG) analysis of the biopsy material yielded silver-enhanced
      mercury grains, primarily in the interstitial Leydig cells. Sections from a
      control patient not exposed to mercury were devoid of mercury grains.

PMID- 8274824
TI  - Excess choline availability: a transient effect on spermatogenesis in the rat.
AB  - The reproductive effects of choline (trimethyl-beta-hydroxyethylammonium) are
      unknown. Excess dietary intake of choline may occur in humans. Adult male rats
      were administered i.p. aqueous choline chloride (25 mg/rat, daily for 12 or 24
      days). Administration of excess choline for 12 days did not significantly alter
      spermatogenesis. Administration for 24 days depleted pachytene spermatocytes
      until posttreatment day 5, while slight proliferation of spermatogonia was noted
      from day 5 onwards. By day 12, the tubules showed almost normal cellular
      associations. It is suggested that perhaps a prolonged administration of excess
      choline may prove to be toxic to male reproduction.

PMID- 8274825
TI  - Diagnosis and treatment of psychiatric and behavioural disorders in mentally
      retarded individuals: the state of the art.
AB  - It is now well known that a higher proportion of people with mental retardation
      show behavioural and psychiatric disorders compared to their non-mentally
      retarded counterparts. However, the exact relationship between psychiatric
      illness and behavioural disorder in this population is far from clear. There are
      problems of using the standard diagnostic and classification categories in this
      population, particularly in those who are severely and profoundly mentally
      retarded. Recently, there have been many novel approaches to this diagnostic
      dilemma, including 'developmental approach' and 'psychodynamic approach'. In the
      Netherlands, the so-called 'developmental-dynamic' approach has been used in the
      diagnosis and treatment of behavioural and psychiatric disorders in the mentally
      retarded. There have also been many treatment approaches, including drug therapy,
      behavioural treatment, psychotherapy, cognitive and social learning. Also the
      Dutch, Swiss and German traditions have extensive experience in the directive
      pedagogical treatment of the mentally retarded.

PMID- 8274826
TI  - Symposium of the European Association for Mental Health in Mental Retardation:
      the mental health of Europeans with learning disabilities. Veldhoven, The
      Netherlands, 8-9 October 1992. Proceedings.

PMID- 8274827
TI  - Mental illness-mental retardation in the United States: policy and treatment
      challenges.
AB  - The purpose of this paper is to present an overview of current trends in the
      field of dual diagnosis in the United States. Policy, programme, diagnostic and
      treatment issues are reviewed. The paper will examine the effects of the social
      policy of deinstitutionalization on people who have a dual diagnosis and will
      offer policy ideas for ameliorating some of the significant obstacles facing this
      population. Exemplary programme models are briefly discussed to illustrate the
      development of effective services. The challenges of assessing psychopathology in
      people with mental retardation are addressed. Several therapy and treatment
      modalities that have proven to be effective with people who have a dual diagnosis
      are also discussed. Lastly, this paper mentions a new community ideology driven
      by the values of consumers choice and satisfaction.

PMID- 8274828
TI  - Mental health services for people with mental retardation: a framework for the
      future.
AB  - The mental health needs of mentally retarded people cannot be met satisfactorily
      with generic mental health services. Specialized services are required. A number
      of different service models have evolved which require evaluation. They include
      subregional units, community-based services with a small admission facility,
      integrated services and specialist teams. Staff working in specialist mental
      health services must be appropriately trained.

PMID- 8274829
TI  - Communicating to care.

PMID- 8274830
TI  - Core temperature measurement: a comparison of rectal, axillary and pulmonary
      artery blood temperature.
AB  - This research study was undertaken to determine the relationship between
      pulmonary artery (PA) blood temperature, rectal temperature and axillary
      temperature for adult patients admitted to an intensive care unit (ICU). 31
      adults had their temperatures monitored. Simultaneous recordings of PA blood
      temperature, rectal temperature and axillary temperature were taken every 4h for
      up to 7 days. The mean difference between rectal and axillary temperature for all
      31 patients was 0.32 degree C. Of the 16 patients who had their PA blood
      temperature monitored mean rectal temperature was 0.1 degree C above PA blood
      temperature and mean axillary temperature was 0.19 degree C below PA blood
      temperature. Very high statistical correlations were obtained which demonstrate
      the strength of the relationships between the three sites (rectal-axillary
      temperature difference R = 0.97; PA blood-rectal temperature difference R = 0.99;
      PA blood-axilla temperature difference R = 0.97). The linear relationship between
      the three sites studied was not found to be affected by age, gender, number of
      temperature samples taken, post/non-operative admission or peripheral
      temperature.

PMID- 8274831
TI  - Application of a pressure area risk calculator in an intensive care unit.
AB  - This study describes the use of a pressure area risk calculator designed
      specifically for intensive care (ICU) patients; the calculator used was that
      developed by Cubbin & Jackson (1991) (Table 1). This scale is a modified Norton
      scale with lower scores indicative of increased risk of pressure sore formation.
      The unit on which this study was undertaken is a six-bedded general adult ICU. A
      highly significant difference in lowest recorded scores was found between the
      group of patients who developed pressure sores compared with the group that did
      not (Mann-Whitney test, p < 0.01). The differences in scores between the two
      groups suggest that the calculator was measuring something useful, but it should
      be stressed that 40% (n = 100) of patients had scores below the threshold value
      and did not develop scores. Risk calculations were decisive in increasing the
      profile of pressure area care within the ICU and for this reason alone their use
      can be justified. There was a pressure sore incidence of 13% with 7% of patients
      having sores prior to admission to the ICU. Of the sores that were noted the
      commonest sites to be affected within intensive care were heels. The sacrum was
      the commonest site for sores that had occurred prior to admission. Pressure sore
      incidence can prove a useful audit tool in the management of pressure area care
      in intensive care, but variations in incidence over time must be examined with
      caution.

PMID- 8274832
TI  - The lecturer practitioner role and the development of intensive care nursing
      practice.

PMID- 8274833
TI  - The management of acute renal failure in the intensive therapy unit.
AB  - The intensive care setting is well recognised as a highly technical area, and
      intensive care nurses are regularly introduced to new and increasingly more
      sophisticated and complicated equipment. The aim of this article is to eliminate
      some of the confusion surrounding the choice of dialysis treatment in acute renal
      failure by reviewing the different types of continuous renal replacement therapy
      (CRRT). Explanation of the principles behind CRRT is expanded by identification
      of the main differences between continuous haemofiltration and continuous
      haemodialysis. Some of the more common problems encountered are discussed and
      suggestions for nursing practice included.

PMID- 8274834
TI  - Nurses' attitudes toward computerised care plans in intensive care. Part 1.
AB  - The purpose of this quantitative study was to measure nurses' attitudes towards
      the use of computerised nursing care plans in intensive care. 41 nurses, working
      in an adult intensive care unit (ICU), completed the closed-structured
      questionnaire. The results of the study revealed that age, type of shift worked,
      length of time qualified and length of time employed on the unit influenced
      nurses' attitudes towards computerised care plans. It was concluded that prior to
      the introduction of a computerised care planning system, it is essential that
      nurses' attitudes are identified. In so doing, a system can be introduced that
      will match the capabilities of and acceptance by the nursing staff.

PMID- 8274835
TI  - Mouth care in an intensive care unit: a review.

PMID- 8274836
TI  - Pre-operative visits by ITU nurses: recommendations for practice.
AB  - Pre-operative visiting by theatre nurses is now policy in many hospitals,
      following an explosion of research studies outlining the benefits to the patient.
      However, the author could find very little available literature on pre-operative
      visiting by intensive therapy unit (ITU) nurses, to patients electively admitted
      to ITU following surgery. The purpose of this project is to explore the need for
      patient information, outline the aims of an ITU nurse's pre-operative visit, and
      discuss the timing of the proposed visit, the information to give the patient,
      the inclusion of the patient's family and the provision of printed literature.
      Finally, recommendations are made for implementing a pre-operative visiting
      service by ITU nurses.

PMID- 8274837
TI  - Cross-cultural communication in an intensive therapy unit.
AB  - Communication should have no barriers, but in an intensive therapy unit (ITU) a
      human's ability to communicate effectively is often severely disrupted due to
      disease and treatment. This is further highlighted in patients who do not speak
      the native language of the place where they are nursed. Problems of this nature
      have been emphasised as more patients are contracted for specialist surgery from
      countries where it is less possible to perform the surgery required, due to
      economic, social or cultural reasons. Patients' and nurses' opinions on
      communications are discussed and a translation booklet is suggested as an aid to
      communication cross-culturally.

PMID- 8274838
TI  - Post-pump delirium.
AB  - Cardiac surgery has many associated complications but the psychological problems
      that can occur are rarely discussed. This literature review focuses on both the
      physiological and psychological causes of post-pump delirium and suggests
      possible recommendations for nursing practice.

PMID- 8274839
TI  - Endotracheal suction for adult, non-head-injured, patients. A review of the
      literature.
AB  - The procedure for endotracheal suctioning was perceived as a problem by the
      members of a quality circle in the intensive care unit (ICU). Endotracheal
      suction, when performed in the unit, appeared to be carried out according to the
      nurses' experience and expertise, and had no formal research backing. An
      extensive literature search was undertaken, and a framework for endotracheal
      suction was formulated based on the available evidence. Some of the aspects of
      endotracheal suction represented in the research evidence appear contradictory,
      and nurses must make a professional judgement about their suction technique based
      on the individual circumstances of patients. The wealth of evidence available
      regarding endotracheal suctioning allows nurses to make an informed decision
      about care.

PMID- 8274840
TI  - Studies on the mechanism of biotin uptake by brush-border membrane vesicles of
      hamster enterocytes.
AB  - Several studies on biotin intestinal transport in the hamster have shown a biotin
      specific carrier, but there are conflicting reports on whether it is transported
      actively, or by facilitated diffusion and on its Na+ dependence. We have studied
      it for the first time using brush-border membrane vesicles (BBMV), with
      concentrations in a more physiological (nanomolar) range and found an overshoot
      component, evidencing a carrier-mediated active process, driving the vitamin
      against a concentration gradient. Uptake was substantially reduced when potassium
      substituted for sodium. When the vesicles were treated with trypsin, Na(+)
      dependent uptake was markedly reduced and the overshoot phenomenon was abolished,
      providing additional evidence for the carrier-mediated transport. The amount of
      uptake in a K+ gradient was considered due to passive diffusion and was about 30%
      of that observed in a Na+ gradient. A similar amount was observed when
      trypsinized vesicles were incubated in this latter gradient. Our results indicate
      that in the hamster's brush border intestinal epithelium, Na(+)-dependent active
      transport is the most important component in the intestinal uptake of biotin at
      nanomolar concentrations.

PMID- 8274841
TI  - Influence of sympathetic tone on the reactivity to indorenate in the external
      carotid vascular bed of the dog.
AB  - The present study was designed to analyze the effects of drugs that interfere
      with sympathetic transmission on the external carotid vasodilator response
      induced by the 5-HT1A receptor agonist, indorenate, in pentobarbital-anesthetized
      dogs. Intracarotid (i.c.) infusions of indorenate (1000 micrograms/l min)
      produced an increase in external carotid blood flow (external C.B.F.) without
      modifying mean arterial blood pressure or heart rate. This effect of indorenate
      was dose-dependently antagonized by intravenous (i.v.) administration of the
      alpha 1-adrenoceptor antagonist, prazosin (1, 3.1, 10, 31 and 100 micrograms/kg),
      the ganglionic blocking agent, mecamylamine (0.031, 0.1, 0.31, 1, 3.1 and 10
      mg/kg) or the 5-HT2 receptor and alpha 1-adrenoceptor antagonist, ketanserin (10,
      31 and 100 micrograms/kg). It is concluded that indorenate-induced increase in
      canine external C.B.F. is dependent on the vascular neurogenic tone.

PMID- 8274842
TI  - Male rat pelvic copulatory movements: computerized analysis of accelerometric
      data.
AB  - Three specifically made computational programs are described. These programs were
      developed in order to delimitate and analyze the accelerometric signals generated
      in relation to the pelvic thrusting performed by the male rat during its
      mounting, intromission, and ejaculation copulatory responses. This methodology
      has allowed us to perform quantitative analysis, not only about duration and
      frequency but also about amplitude or vigor of pelvic thrusting trains. We found
      that during long ejaculation, the extravaginal pelvic movement had a
      significantly higher amplitude than that of the intravaginal movements.

PMID- 8274843
TI  - Vascular effects of ipsapirone are related with subtypes of alpha 1-adrenergic
      receptors.
AB  - The aim of this study was to provide further evidence about the participation of
      alpha 1-adrenoceptors in the vascular responses elicited by ipsapirone. This 5
      HT1A agonist displayed vasodilator activity only when aortic rings were
      precontracted by alpha-adrenergic compounds. The relaxant effect was particularly
      evident when rings were precontracted with methoxamine (selective alpha 1A
      adrenergic agonist). On the other hand, ipsapirone but not chloroethylclonidine
      (selective alpha 1B-adrenergic antagonist), clearly displaced norepinephrine and
      methoxamine vasocontractile concentration-response curves to the right. Finally,
      ipsapirone protected the alpha-adrenoceptors form the irreversible blockade
      provoked by phenoxybenzamine, as judged by the norepinephrine contraction and
      stimulated phosphatidylinositil labeling. Accordingly the relaxant effect
      elicited by ipsapirone in aortic rings precontracted with alpha-adrenergic
      agonists and the protective action against blockade by phenoxybenzamine shown by
      this agent are proof of its ability to occupy alpha 1-adrenoceptors.
      Specifically, alpha 1A-adrenergic receptors seem to be involved in ipsapirone
      vascular effects, since this agent selectively relaxed aortic preparation
      precontracted with methoxamine and unlike chloroethylclonidine, clearly inhibited
      the contractile effect of this agonist. In summary, the present findings can be
      explained by accepting that ipsapirone may act as an antagonist at alpha 1A
      adrenoceptors.

PMID- 8274844
TI  - Effects of acute and chronic toluene inhalation on behavior, monoamine metabolism
      and specific binding (3H-serotonin and 3H-norepinephrine) of rat brain.
AB  - The present study deals with the effect of chronic toluene inhalation (30,000
      40,000 ppm in air, 15 min/day for 30 days) that induced abnormal behavior states
      resembling the serotonin syndrome in rats: resting tremor, hindlimb abduction,
      Straub tail, head weaving and rigidity. The head weaving latencies were
      significantly decreased when assessed at 15 and 30 days of exposure to toluene
      vapors. The sequence pattern signs of serotonin syndrome were changed after 15
      and 30 days of exposure, indicating possible cumulative effects and/or tolerance
      development. There were no changes in concentrations of indolamine and
      catecholamine compounds in different parts of the rat brain (cerebral cortex,
      midbrain, brainstem and cerebellum) as influence of chronic toluene exposure.
      Examination of specific serotonin ((3H)-5HT) to crude synaptic membranes prepared
      from rat brains and subjected to chronic toluene inhalation revealed a very high
      increased value in apparent Kd (30.7 +/- 15) with respect to its air control (9.7
      +/- 2.3) and baseline control (5.8 +/- 3.2). This difference was highly
      significant (p < 0.02). There were no changes in apparent Bmax of specific (3H)
      5HT binding sites. On the other hand (3H)-NE binding of rat brain studies did not
      show any difference either in apparent Kd or apparent Bmax. These results
      indicate that serotonin syndrome may be a consequence of changes of serotonergic
      mechanism, specifically a reduced affinity in specific (3H)-5HT binding sites.

PMID- 8274845
TI  - Cardiodepressor effects of 7-O-demethylisothalicberine, bisbenzylisoquinoline
      alkaloid isolated from Berberis chilensis.
AB  - 7-O-demethylisothalicberine (7-O-DI), an alkaloid isolated from Berberis
      chilensis Gillies ex Hook, induces a negative inotropism and chronotropism on
      guinea pig isolated atria (IC50 = 1.5 x 10(-4) and 1.8 x 10(-4) M, respectively).
      As these effects were not antagonized by propranolol, 7-O-DI inhibition of
      isoproterenol-induced atrial activation seems to be attained through a mechanism
      distinct of beta-receptor blockade. A probable cholinergic mechanism of action
      was also ruled out. 7-O-DI atrial effects were completely reversed by a 50%
      increase of calcium concentration. The spontaneous frequency of rat sinus node
      was also deeply modified by 7-O-DI, in accordance with previous results obtained
      in frog cardiac pacemaker cells. It is concluded that 7-O-DI should perform its
      pharmacological action through calcium entry blockade. These results open
      expectations for future research about probable therapeutic use for 7-O-DI.

PMID- 8274846
TI  - Entamoeba histolytica: inhibition of malic enzyme and alcohol dehydrogenase by
      (+/- )-, (+)-, and (-)- gossypol.
AB  - Gossypol, a natural racemic mixture with action on NADP- and NAD-oxidoreductases
      from diverse species, has been proposed as a possible antiamebic medication
      considering several of its pharmacological properties. In this study it was found
      that malic enzyme and alcohol dehydrogenase from Entamoeba histolytica are
      strongly inhibited by (+/-)-gossypol, and both (+)- and (-)- enantiomers. The
      inhibition was of the noncompetitive type among their respective substrates in
      all cases. The (+/-), (+)-, (-)-gossypol half-maximal inhibitory concentrations
      (IC50) for the malic enzyme were 3.71, 13.37 and 1.03 microM, and against the
      alcohol dehydrogenase 79.64, 124.43 and 42.56 microM, respectively. Therefore,
      the (-) enantiomer resulted 3.6 and 13.0 times more potent than the racemic
      mixture and (+)-gossypol, respectively, to inhibit the malic enzyme, and 1.9
      times and 2.9 times more potent than the racemic mixture and (+)-gossypol,
      respectively, against the alcohol dehydrogenase. Accordingly, one possible
      mechanism of the antiamebic effect of gossypol could be the inhibition of vital
      NADP-dependent enzymes as those analyzed in this study.

PMID- 8274847
TI  - Tru-cut needle biopsy of subcutaneous fat in the diagnosis of secondary
      amyloidosis in rheumatoid arthritis.
AB  - In order to investigate the presence of secondary amyloidosis in patients with
      rheumatoid arthritis (RA), we performed an abdominal subcutaneous fat biopsy with
      a tru-cut needle in 50 patients. The tissue was stained with Congo red and was
      observed with polarized light microscopy. We found amyloid deposits in 78% of our
      patients. We randomly selected ten patients with a positive biopsy and a second
      procedure was performed. Tissues were studied with electron microscopy. We found
      unbranched fibrils characteristic of amyloid in all of them. We found a direct
      correlation with rheumatoid factor titers: the more intense the amyloid deposit,
      the higher the rheumatoid factor titers (p < 0.001). We did not find any
      correlation between amyloid deposits and clinical manifestations of disease.
      Amyloid deposits in RA are more frequent than previously thought, and their
      clinical importance remains to be determined.

PMID- 8274848
TI  - Family study of obsessive-compulsive disorder in a Mexican population.
AB  - Twenty seven obsessive-compulsive disorder (OCD) patients were studied at the
      Instituto Mexicano de Psiquiatria in Mexico City. This is the first sample of OCD
      patients studied in Latin America. There was a significant sex ratio difference
      and a significant difference in the type of obsessions and compulsions displayed
      by males and females. Co-morbidity data demonstrated a high frequency of
      obsessive-compulsive personality disorders, depression, sexual abuse, suicidal
      attempts and neurological damage. Approximately one third of OCD cases
      demonstrated a positive family history. There was a higher than expected
      frequency of first degree relatives affected with OCD. In addition, this study
      may support the hypothesis that OCD and tics are genetically related.

PMID- 8274849
TI  - Modification of the Smith and Naylor technique for the identification of
      ferruginous bodies.
AB  - Smith and Naylor's technique has been successfully used by many authors around
      the world to recover inorganic particles from the lungs. In this short report we
      compare the results of counting inorganic particles recovered from human lung
      tissue by two different methods: Smith and Naylor's technique and a modification
      to it. We used ferruginous bodies (FB) as markers for inorganic particles and we
      compared the results of the FB counts in both methods. In the traditional
      technique the interface formed in the 1:1 ethanol-chloroform mixture is
      discharged and FB are counted only in the formed pellet. Our modification also
      quantified FB in the interface fraction. Post-mortem samples from each of the
      lung lobes were taken from 22 individuals, totalling 198 samples. Each sample was
      digested in liquid commercial bleach and processed by both techniques. Our
      results showed that the modified technique was more sensitive in the detection of
      FB than the traditional method, with 16 out of 22 individuals showing positive
      identification against 14 out of 22, respectively. Furthermore, the modified
      technique proved not only to be more sensitive, but also almost twice as
      accurate: 49 FB/g vs. 26.7 FB/g of dry tissue.

PMID- 8274850
TI  - Decreased adenosine deaminase activity in peripheral lymphocytes of patients
      suffering from amebic liver abscess.
AB  - Amebic liver abscess (ALA) is associated with a state of transient suppression of
      cell-mediated immunity (CMI). T4 helper-inducer cell number is reported to be
      reduced. However, little is known of the reason for such reduction. Adenosine
      deaminase (ADA), an enzyme of salvage pathway in purine metabolism, is reported
      to be essential for the normal growth, differentiation and proliferation of T
      lymphoid cells. In a pilot study we estimated the ADA levels in the peripheral
      lymphocytes of ALA patients. It was observed that the mean enzyme level in
      patients was 223.98 +/- 51.81 as against 405 +/- 38.12 in controls. The
      significantly low levels (p < 0.05) of enzyme in patients' lymphocytes may
      possibly explain the reduction of T4 helper-inducer cells reported in these
      cases. This parameter, if further evaluated, can serve as a differentiation
      marker between helper and suppressor T-cell subsets.

PMID- 8274851
TI  - Mechanistic and structural complexity in the site-specific recombination pathways
      of Int and FLP.
AB  - This review focuses on two of the approximately 30 members of the diverse Int
      family of site-specific recombinases. The lambda recombination system represents
      those reactions involving accessory proteins and a complex higher-order
      structure. The FLP system represents the most streamlined reactions and has been
      the subject of detailed and informative studies on the mechanisms of DNA cleavage
      and ligation.

PMID- 8274852
TI  - Protein-DNA assemblies controlling lytic development of bacteriophage Mu.
AB  - Recent analysis of the mechanism and regulation of transposition by bacteriophage
      Mu has emphasized the importance of controlled assembly of specific protein-DNA
      complexes. Both the Mu transposase and the Mu repressor engage in multiple
      protein-protein and protein-DNA interactions that modulate the outcome of a phage
      infection.

PMID- 8274853
TI  - SOS mutagenesis.
AB  - In Escherichia coli, UV and many chemicals appear to cause mutagenesis by a
      process of translesion synthesis that requires some form of DNA polymerase III
      and the SOS-regulated proteins UmuD, UmuC and RecA. An analysis of SOS
      mutagenesis offers insights into the molecular basis of induced mutagenesis and
      into mechanisms of DNA damage tolerance.

PMID- 8274854
TI  - Restructuring of DNA sequences in the germline genome of Oxytricha.
AB  - Most genes in the germline genome of hypotrichous ciliates are crippled by the
      presence of interrupting sequences. Some genes are additionally impaired because
      their sequences are in disorder. These gene defects are corrected when germline
      chromosomal DNA sequences are amplified, cut, spliced, reordered, and eliminated
      to produce somatic DNA.

PMID- 8274855
TI  - Developmentally regulated processing and replication of the Tetrahymena rDNA
      minichromosome.
AB  - The ribosomal DNA locus of Tetrahymena thermophila undergoes a dramatic series of
      developmentally regulated processing events to generate the amplified rDNA
      minichromosome during formation of the somatic macronucleus. DNA transformation
      and classical genetic approaches have identified cis-acting elements that
      regulate rDNA processing in the developing macronucleus and subsequent vegetative
      rDNA maintenance.

PMID- 8274856
TI  - Meiotic recombination in yeast.
AB  - Over the past several years, the yeast Saccharomyces cerevisiae has proven to be
      an extremely useful model system for understanding how cells acquire high
      recombinational ability during meiosis. Due to recent advances in the physical
      monitoring of DNA intermediates during meiosis, new cytological methods for
      visualization of chromosomes during pairing and exchange, and progress in the
      identification and analysis of recombination-defective mutants, a general picture
      of the order and dependencies of specific recombination events is now emerging.

PMID- 8274857
TI  - Lineage-dependent mating-type transposition in fission and budding yeast.
AB  - The basis of cellular differentiation is perhaps best understood in the yeast
      mating-type switching system. The yeast cell produces daughter cells that differ
      from each other or from their parent cell via developmentally regulated genomic
      rearrangements. Recent experiments on cell-type determination in fission yeast
      have revealed that this process is determined by the inheritance of specific
      parental chromosome strands by the progeny cells.

PMID- 8274858
TI  - The structure and function of yeast ARS elements.
AB  - The past year has seen significant advances in our understanding of the structure
      and function of yeast ARS elements. These elements, some of which function as
      chromosomal origins of DNA replication, are modular in structure. An essential
      domain, the ARS consensus sequence, binds a multiprotein complex that might be
      the long-sought initiator protein. The flanking domain contains a DNA unwinding
      element and a binding site for a multifunctional protein that acts as a
      replication enhancer.

PMID- 8274859
TI  - Telomeres and telomerases.
AB  - The ends of eukaryotic chromosomes are defined by specialized nucleoprotein
      complexes called telomeres. Telomeres impart stability to the genome and are of
      general interest due to their unique structure and unconventional mode of
      synthesis. Recent work has identified new components of the telomere complex and
      expanded our understanding of the role of terminal structures in maintaining cell
      viability.

PMID- 8274860
TI  - Transcription and DNA supercoiling.
AB  - Transcription and supercoiling of the DNA template are interrelated. This review
      summarizes recent progress in the study of how template topology affects
      transcription, and how transcription affects template topology inside wild-type
      and DNA topoisomerase mutant cells. The interplay between DNA supercoiling and
      transcription raises interesting questions on the regulation of adjacent genes,
      the organization of intracellular DNA, and the coupling between transcription and
      other cellular processes involving DNA.

PMID- 8274861
TI  - Conserved features of yeast and mammalian mitochondrial DNA replication.
AB  - Mammalian mitochondrial DNA replication is initiated by the processing of RNA
      transcripts derived from an upstream promoter to create RNA primers for DNA
      replication. In the yeast Saccharomyces cerevisiae, mitochondrial ori/rep
      sequences contain a transcription promoter upstream of the site of transition
      from RNA to DNA synthesis, suggesting a common mode of replication initiation.
      Recent research has identified features in the mode and machinery of DNA
      replication conserved from yeast to mammals.

PMID- 8274862
TI  - Bacterial chromosome origins of replication.
AB  - Bacteria regulate chromosomal replication from one specific origin. We compare
      the regulatory requirements, DNA structures, and biochemical properties of the
      prototypic Escherichia coli origin with those of evolutionarily distant Bacillus
      subtilis and Caulobacter crescentus origins. The ubiquitous DnaA protein is a
      major regulator of all three bacterial origins. Unique features of these origins,
      however, may reflect specific regulatory requirements placed on them.

PMID- 8274863
TI  - Escherichia coli cell division.
AB  - Recent progress in the molecular analysis of bacterial septation and chromosome
      partitioning suggests that these processes may involve cytoskeletal elements
      previously thought to be present only in eukaryotic cells. The continued
      biochemical and genetic analysis of key proteins, such as the tubulin-like FtsZ,
      should lead to further unravelling of the regulation and mechanism of bacterial
      cell division.

PMID- 8274864
TI  - Chromosome partition in Escherichia coli.
AB  - The past year has seen important genetic and biochemical advances in our
      understanding of the mechanisms that are involved in chromosome partition into
      two daughter cells in Escherichia coli. Topoisomerase IV and XerCD recombinase
      have been shown to be required for the unlinking of replicated chromosomes. MukB,
      an alpha-helical coiled-coil protein, has been shown to be involved in chromosome
      partition, and this is the first candidate for a bacterial motor protein. Another
      protein, FtsZ, has been shown to form a constriction ring in cell division and
      may also relate to chromosome partition.

PMID- 8274865
TI  - Regulation of chromosome dynamics in microorganisms.

PMID- 8274866
TI  - The politics of abortion: a historical perspective.
AB  - An analysis of the capture of the Republican party and the national agenda from
      the late 1970s into the 1990s by a coalition of political and religious
      conservatives.

PMID- 8274867
TI  - Religion and abortion: Roman Catholicism lost in the pelvic zone.

PMID- 8274868
TI  - Life on the front lines.

PMID- 8274869
TI  - Antiabortion violence: causes and effects.

PMID- 8274870
TI  - Providing controversial health care: abortion services since 1973.

PMID- 8274871
TI  - Who will do the abortions?

PMID- 8274872
TI  - Beyond Roe, after Casey: the present and future of a "fundamental" right.

PMID- 8274874
TI  - Medical schools and abortion.

PMID- 8274873
TI  - Mifepristone (RU 486) for induced abortion.

PMID- 8274875
TI  - Bone mineral density of female athletes in different sports.
AB  - Anthropometry, training history, cardiorespiratory and muscular performance
      capacity, and bone mineral density (BMD) were studied in female orienteers (n =
      30), cross-country skiers (n = 28), cyclists (n = 29), weight lifters (n = 18)
      and in a reference group (n = 25). BMD was measured at lumbar spine, femoral
      neck, distal femur, patella, proximal tibia, calcaneus and distal radius by dual
      energy X-ray absorptiometry. The weight lifters had significantly higher weight
      adjusted BMD (P < 0.001) than the referents at all sites (9-26%) except in
      femoral neck and calcaneus. Of the endurance athletes, the orienteers were the
      only group which had significantly higher BMD (P < 0.05) than referents, only at
      distal femur (5%) and proximal tibia (5%). BMD did not differ significantly at
      any skeletal site between subjects with different calcium intake. Weight training
      seems to provide more effective osteogenic stimulus than endurance training. The
      differences in BMD at different sites between the groups were consistent with
      specificity of the stimulus to the training of the studied sports.

PMID- 8274876
TI  - Inhibition of 1,25(OH)2D production by hypercalcemia in osteitis fibrosa cystica:
      influence on parathyroid hormone secretion and hungry bone disease.
AB  - Primary hyperparathyroidism is usually associated with normal or elevated serum
      1,25-dihydroxyvitamin D [1,25(OH)2D] levels. We report a 63-year-old patient with
      extreme hypercalcemia (ionized serum calcium, 2.51 mmol/l; normal range, 1.19
      1.36), very high serum concentrations of intact immunoreactive parathyroid
      hormone (iPTH) (145 pmol/l; normal range, 1-6.8), radiological lesions of
      osteitis fibrosa cystica, only mildly impaired renal function (creatinine
      clearance, 69 ml/min/m2) and very low serum levels of 1,25(OH)2D (28.8 pmol/l;
      normal range, 72-120). Presurgery normalization of the calcemia with normal
      saline, salmon calcitonin and pamidronate caused an increase in 1,25(OH)2D serum
      concentration to 228.3 pmol/l. A negative correlation could be established
      between ionized calcium and 1,25(OH)2D levels during that period (r2 = 0.80, P <
      0.04). While serum calcium decreased with treatment, serum iPTH also decreased to
      48.6 pmol/l, suggesting some 1,25(OH)2D inhibition of parathyroid adenoma
      function. Serum alkaline phosphatase also rose from 309 to 390 units/l (normal
      range, 25-97), suggesting the beginning of resolution of her osteitis fibrosa
      cystica prior to surgery. Surgical removal of a parathyroid adenoma was
      associated with a decrease in serum calcium and iPTH levels. To our surprise, the
      hypocalcemia could be managed easily with 1500 mg of oral calcium carbonate
      daily, even if the hungry bone disease became more active with an increase in
      alkaline phosphatase to 486 units/l. This was explained by the very high levels
      of serum 1,25(OH)2D (> 200 pmol/l) which prevailed in the postsurgery period and
      were probably related to decreased bone resorption and increased bone formation.
      This case illustrates that normalizing serum calcium prior to surgery in patients
      with primary hyperparathyroidism and osteitis fibrosa cystica can be highly
      beneficial.

PMID- 8274877
TI  - Comparison between the lengths of individual osteoid seams and resorption
      cavities in human iliac crest cancellous bone.
AB  - The current concept of bone remodelling is based on the belief that bone
      resorption and formation are coupled both in time and space; this implies that
      the surface extent of bone eroded in a bone remodelling unit would approximate to
      the surface extent of the osteoid seam formed subsequently. The greater total
      surface extent of osteoid as opposed to erosion is generally attributed to the
      longer life-span of bone formation, but no comparison of the length of eroded
      surface and osteoid seam within individual bone remodelling units has been
      reported. In this study we have compared the length of individual osteoid seams,
      resorption cavities and bone structural units in iliac crest trabecular bone
      obtained from normal subjects and from patients with renal osteodystrophy. Values
      for osteoid seam and bone packet length were significantly greater than
      resorption cavity length in both the normal and patient groups (P < 0.001), the
      ratio of osteoid seam and eroded length being similar in the two groups (1:0.44
      and 1:0.40, respectively). These results indicate that the discrepancy between
      total osteoid and eroded surface extent cannot be wholly explained on the basis
      of a longer formation life-span. Possible additional explanations include
      underestimation of eroded surface by light microscopic techniques, initiation of
      bone formation within a cavity before the completion of resorption, the presence
      of arrested resorption cavities, non-random distribution of resorption cavities
      on the trabecular surface and bone formation on quiescent bone surfaces.

PMID- 8274878
TI  - Modulation of parathyroid hormone-sensitive adenylate cyclase in ROS 17/2.8 cells
      by dexamethasone 1,25-dihydroxyvitamin D3 and protein kinase C.
AB  - We tested whether the protein kinase C (PKC) modulation of PTH-sensitive
      adenylate cyclase in ROS 17/2.8 cells is affected by the glucocorticoid
      dexamethasone and the vitamin D hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3].
      Basal and PTH- and forskolin-stimulated adenylate cyclase activities were
      determined in the presence or absence of 100 nM phorbol 12-myristate 13-acetate
      (PMA), the activator of PKC, in ROS 17/2.8 cells that had been previously
      cultured with or without dexamethasone or 1,25(OH)2D3. Dexamethasone treatment
      increased the basal, PMA-, PTH-, (PTH + PMA)- and (forskolin + PMA)-sensitive
      adenylate cyclase while 1,25(OH)2D3 decreased these effects. The stimulatory and
      inhibitory effects were dose-dependent with respect to dexamethasone and
      1,25(OH)2D3, respectively. Dexamethasone increased, while 1,25(OH)2D3 decreased
      the maximal activity of both PTH-sensitive and PKC-modulated PTH-sensitive
      adenylate cyclase without affecting the half-maximal concentration (ED50) of PTH
      required for the activation of the enzyme. Additionally, dexamethasone,
      1,25(OH)2D3 and PKC did not affect each other's ED50. Our results suggest that
      the effects of dexamethasone, 1,25(OH)2D3 and PKC on PTH-sensitive adenylate
      cyclase in ROS 17/2.8 cells are independent of each other.

PMID- 8274879
TI  - Bone mineral deposition in mice selected for body conformation.
AB  - Bone mineral content was investigated in 2 lines of mice (CBi/C and CBi/L) that
      carry different biomasses per unit of skeletal weight. These lines also differ in
      their femoral histomorphometry and bone biomechanics. The logarithmic form of the
      allometric equation describing the relationship between ash weight and body
      weight was used to compare the mineral content in both sexes of these genotypes.
      No statistical difference was observed in the slopes of the curves describing the
      changes in bone mineral content as a function of age. Both lines had greater
      values than the line for control animals. The selected lines did differ
      significantly in the intercepts of the curves on the y-axis. An independent
      determination of both allometric parameters by genetic factors is proposed. Genes
      or groups of genes could affect mineral deposition in two ways: one could produce
      positional changes of the allometric curves in the embryo but leave their
      postnatal slopes unchanged; another could modify the postnatal slope of the
      curve. The combined expression of these different genes should be important in
      preserving homeostatic functioning of the organism.

PMID- 8274880
TI  - Cross-mating study on bone mass in the spontaneously osteoporotic mouse (SAM
      P/6).
AB  - Genetic control of bone mass in the spontaneously osteoporotic mouse (SAM-P/6)
      was examined by classical cross-mating experiments, in which SAM-P/2 with a high
      bone mass was used as a control. Femoral bone mass corrected by size (= bone
      density) was assayed photometrically. F1 hybrids exhibited intermediate values
      between those of the two parental strains, i.e. higher than SAM-P/6 and lower
      than SAM-P/2. F2 hybrids showed a more widely distributed pattern with a mean
      value quite similar to that of F1 hybrids. The values for backcrosses were
      between those of F1 and the respective parental strains. They did not show
      segregations expected in cases of a single-gene control. Numerical analysis of
      data distribution in each generation suggested that strain-specific bone mass in
      these strains of mice is inherited as a polygenic characteristic and controlled
      by a relatively small number of genes.

PMID- 8274881
TI  - Characterization of calcium transport in the luminal and the basolateral membrane
      from kidney cortex of hypercalcemic rats bearing the Walker 256 carcinosarcoma.
AB  - The Walker 256 (W256) carcinosarcoma did not significantly modify calcium uptake
      by brush border membrane (BBM) vesicles in the kidney of the host rat, compared
      with that in membranes isolated from control animals. However, it showed a
      tendency to increase at near equilibrium in W256 tumor-host rats, associated with
      a decreased BBM protein content. ATP-dependent calcium influx by basolateral
      membrane (BLM) vesicles from W256 tumor-bearing rats was also increased compared
      with that in control BLM. This stimulation was due to a decreased Km for calcium.
      Passive calcium permeability or the Na+/Ca2+ exchanger were unchanged in BLM from
      W256 tumor-host rats compared with control BLM. Pre-stimulation of control rat
      cortical tubules with either 10(-7) M parathyroid hormone-related protein (PTHrP)
      (1-34) or 10(-4) M N6,2'-O-dibutiryl cyclic AMP before BLM isolation, did not
      modify the ATP-dependent calcium uptake by BLM vesicles compared with control
      membranes. However, our results do not rule out that the stimulated ATP-dependent
      calcium influx in BLM from W256 tumor-host rats could be mediated by the
      interaction among PTHrP and other humoral factors. Our findings suggest a
      possible mechanism for the increased renal calcium reabsorption in this animal
      model for humoral hypercalcemia of malignancy.

PMID- 8274882
TI  - Third World debt.

PMID- 8274883
TI  - Prostitution: would legalisation help?

PMID- 8274884
TI  - How safe is tamoxifen?

PMID- 8274885
TI  - Long term management of patients after splenectomy.

PMID- 8274886
TI  - Alcohol and heart disease: the implications of the U-shaped curve.

PMID- 8274887
TI  - Brief interventions for alcohol misuse.

PMID- 8274888
TI  - WHO to concentrate HIV strategy on vaginal microbicide.

PMID- 8274889
TI  - Interactions between people's diet and their smoking habits: the dietary and
      nutritional survey of British adults.
AB  - OBJECTIVE: To compare diet, nutrient intakes, and biochemical measures between
      smokers and non-smokers. DESIGN: Analysis of data collected in cross sectional
      survey conducted in 1986 and 1987. Subjects were recruited from electoral wards
      in England, Wales, and Scotland to reflect the regional distribution of the
      population. SUBJECTS: 2197 subjects (70% of those asked) aged between 16 and 64
      undertook dietary assessment. Of these, 1842 subjects were considered to have
      kept a record typical of their usual dietary intake and had given data on
      smoking, and their results were analysed: 1224 non-smokers (631 men), 359 light
      smokers (166 men), and 259 heavy smokers (153 men). MAIN OUTCOME MEASURES:
      Differences in dietary, nutrient, and biochemical measures between nonsmokers and
      smokers. RESULTS: Smokers ate more white bread, sugar, cooked meat dishes,
      butter, and whole milk and less wholemeal bread, high fibre breakfast cereals,
      fruit, and carrots. Smokers had lower intakes of polyunsaturated fat, protein,
      carbohydrate, fibre, iron, carotene, and ascorbic acid. Adjusting for other
      covariates did not substantially alter the pattern of intakes. At the same
      dietary intake of carotenoids smokers were more likely to have lower circulating
      serum beta carotene concentrations than non-smokers. CONCLUSIONS: The diet and
      nutrient intakes and circulating levels of nutrients of smokers were different
      from those of non-smokers. Smokers were more likely to have an imbalance between
      the dietary intake of antioxidant nutrients and the metabolic demand for
      antioxidant protection. This imbalance is likely to make smokers more susceptible
      to oxidative damage. Smokers are at increased risk of chronic disease because
      their diets are different and because smoking creates an altered pattern of
      demand for specific nutrients. The diets of smokers not only fail to meet the
      unusual requirements for specific nutrients to satisfy the altered pattern of
      demand but are likely to exacerbate the damage caused by smoking.

PMID- 8274890
TI  - Associations of serum lipid concentrations and obesity with mortality in women:
      20 year follow up of participants in prospective population study in Gothenburg,
      Sweden.
AB  - OBJECTIVE: To examine association of different measures of serum lipid
      concentration and obesity with mortality in women. DESIGN: Prospective
      observational study initiated in 1968-9, follow up examination after 12 years,
      and follow up study based on death certificates after 20 years. SETTING:
      Gothenburg, Sweden. SUBJECTS: 1462 randomly selected women aged 38-60 at start of
      study. MAIN OUTCOME MEASURES: Total mortality and death from myocardial
      infarction as predicted by serum cholesterol and triglyceride concentrations,
      body mass index, and ratio of circumference of waist to circumference of hips.
      RESULTS: 170 women died during follow up, 26 from myocardial infarction. Serum
      triglyceride concentration and waist:hip ratio were significantly associated with
      both end points (relative risk of total mortality for highest quarter of
      triglyceride concentration v lower three quarters 1.86 (95% confidence interval
      1.30 to 2.67); relative risk for waist:hip ratio 1.67 (1.18 to 2.36)). These
      associations remained after adjustment for background variables. Serum
      cholesterol concentration and body mass index were initially associated with
      death from myocardial infarction, but association was lost after adjustment for
      background variables. Serum triglyceride concentration and waist:hip ratio were
      independently predictive of both end points (logistic regression coefficient for
      total mortality for triglyceride 0.514 (SE 0.150), p = 0.0006; coefficient for
      waist:hip ratio 7.130 (1.92), p = 0.0002) whereas the other two risk factors were
      not (coefficient for total mortality for cholesterol concentration -0.102
      (0.079), p = 0.20; coefficient for body mass index -0.051 (0.027), p = 0.05).
      CONCLUSIONS: Lipid risk profile appears to be different in men and women given
      that serum triglyceride concentration was an independent risk factor for
      mortality while serum cholesterol concentration was not. Consistent with previous
      observations in men, localisation of adipose tissue was more important than
      obesity per se as risk factor in women.

PMID- 8274891
TI  - Case-control study of prostatic cancer in employees of the United Kingdom Atomic
      Energy Authority.
AB  - OBJECTIVE: To investigate the relation between risk of prostatic cancer and
      occupational exposures, especially to radionuclides, in employees of the United
      Kingdom Atomic Energy Authority. DESIGN: Case-control study of men with prostatic
      cancer and matched controls. Information about sociodemographic factors and
      exposures to radionuclides and other substances was abstracted and classified for
      each subject from United Kingdom Atomic Energy Authority records without
      knowledge of who had cancer. SUBJECTS: 136 men with prostatic cancer diagnosed
      between 1946 and 1986 and 404 matched controls, all employees of United Kingdom
      Atomic Energy Authority. MAIN OUTCOME MEASURES: Documented or possible
      contamination with specific radionuclides. RESULTS: Risk of prostatic cancer was
      significantly increased in men who were internally contaminated with or who
      worked in environments potentially contaminated by tritium, chromium-51, iron-59,
      cobalt-60, or zinc-65. Internal contamination with at least one of the five
      radionuclides was detected in 14 men with prostatic cancer (10%) and 12 controls
      (3%) (relative risk 5.32 (95% confidence interval 1.87 to 17.24). Altogether 28
      men with prostatic cancer (21%) and 46 controls (11%) worked in environments
      potentially contaminated by at least one of the five radionuclides (relative risk
      2.36 (1.26 to 4.43)); about two thirds worked at heavy water reactors (19 men
      with prostatic cancer and 32 controls (relative risk 2.13 (1.00 to 4.52)).
      Relative risk of prostatic cancer increased with increasing duration of work in
      places potentially contaminated by these radionuclides and with increasing level
      of probable contamination. Prostatic cancer was not associated with exposure to
      plutonium, uranium, cadmium, boron, beryllium, or organic or inorganic chemicals.
      CONCLUSIONS: Risk of prostatic cancer risk was increased in United Kingdom Atomic
      Energy Authority workers who were occupationally exposed to tritium, 51Cr, 59Fe,
      60Co, or 65Zn. Exposure to these radionuclides was infrequent, and their separate
      effects could not be evaluated.

PMID- 8274892
TI  - Antibiotic induced fatigue.

PMID- 8274893
TI  - Pneumococcal vaccination after splenectomy: survey of hospital and primary care
      records.

PMID- 8274894
TI  - Organising midwifery led care in The Netherlands.
AB  - The growing pressure for changes in the care available for pregnant women at low
      risk found a voice in the report on maternity services from the House of Commons
      Health Committee published in February 1992. The demand for greater autonomy and
      responsibility by midwives and the need to rationalise medical working practices
      in the light of changes in junior doctors' hours adds urgency to the need to find
      ways of instituting change while maintaining safety. A visit to the Netherlands
      allowed first hand evaluation of aspects of the Dutch model of maternity care of
      relevance to establishing midwifery led care for women with uncomplicated
      pregnancies in the United Kingdom.

PMID- 8274895
TI  - Filling the lacuna between research and practice: an interview with Michael
      Peckham. Interview by Richard Smith.

PMID- 8274896
TI  - Increased risk of sepsis after splenectomy.

PMID- 8274897
TI  - ABC of emergency radiology. The abdomen--II.

PMID- 8274898
TI  - Treatment of urinary tract stones.
AB  - Replacement of open surgery with minimally invasive techniques for treating
      stones in the renal tract has greatly reduced patients' morbidity and mortality
      and the period of hospitalisation and convalescence. Extracorporeal shockwave
      lithotripsy does not require anaesthesia and requires little analgesia so that
      treatment can be given on an outpatient basis, and there is no wound to heal.
      Only a small puncture site is needed for percutaneous endoscopic lithotomy, and
      with the advent of prophylactic antibiotics there are few complications. Of renal
      stones, about 85% can now be successfully treated by extracorporeal lithotripsy
      alone, and almost all of the stones too large or hard for lithotripsy can be
      treated endoscopically, with ultrasonic or electrohydraulic probes being used to
      fragment the stone. Stones in the upper and lower thirds of the ureter can be
      treated by extracorporeal lithotripsy, but stones in the middle third, which
      cannot normally be visualised to allow focusing of the shockwaves, usually
      require ureteroscopy. Nearly all bladder stones can be treated by transurethral
      endoscopy with an electrohydraulic probe. Only the largest renal tract stones
      still require open surgery.

PMID- 8274899
TI  - German blood scandal.

PMID- 8274900
TI  - Impact of menopausal symptoms. Effect on quality of life exaggerated.

PMID- 8274901
TI  - Impact of menopausal symptoms. Study perpetuates false impression.

PMID- 8274902
TI  - Free radicals and vascular disease.

PMID- 8274903
TI  - Intraoperative use of thrombolytic agents. Procedure requires appropriate
      imaging.

PMID- 8274904
TI  - Taking babies' rectal temperature.

PMID- 8274905
TI  - Community treatment of severe psychiatric illness.

PMID- 8274906
TI  - Zidovudine dosage.

PMID- 8274907
TI  - Which insufflation gas for laparoscopy.

PMID- 8274908
TI  - Oral cholera vaccine well tolerated.

PMID- 8274909
TI  - Chronic constipation in elderly patients.

PMID- 8274910
TI  - Value of confidential inquiries.

PMID- 8274911
TI  - Fatal anaphylaxis due to food.

PMID- 8274912
TI  - Acromegaly: treatment after 100 years.

PMID- 8274913
TI  - Genetic testing and insurance.

PMID- 8274914
TI  - Benign paroxysmal positional vertigo.

PMID- 8274915
TI  - Sunbeds and the pursuit of the year round tan.

PMID- 8274916
TI  - Making murder sound respectable.

PMID- 8274917
TI  - Revised guidelines on preoperative autologous blood donation.

PMID- 8274918
TI  - France rejects HIV screening.

PMID- 8274919
TI  - Excluding blood donors at high risk of HIV infection in a west African city.
AB  - OBJECTIVE: To examine the potential impact of deferral of blood donors at high
      risk of HIV infection in a west African city where blood is screened for HIV
      antibodies but no other special measures are taken to protect the blood supply.
      DESIGN: Cross sectional study. SETTING: National Blood Transfusion Centre and
      Project RETRO-CI, an international collaborative AIDS research project, Abidjan,
      Cote d'Ivoire. SUBJECTS: 1257 male first time blood donors. INTERVENTIONS: Blood
      donors were interviewed about demographic and behavioural characteristics and
      tested for HIV antibodies by enzyme immunoassay and, if positive, synthetic
      peptide based tests. MAIN OUTCOME MEASURES: HIV antibody status in relation to
      presence of behavioural risk factors; calculation of sensitivity, specificity,
      and predictive values of specific criteria for excluding HIV infected donors.
      RESULTS: The overall prevalence of HIV infection was 11.4%. The most important
      risk factors for HIV positivity were prostitute contact and being aged 30-39
      years. For identifying seropositive donors individual criteria had sensitivity,
      specificity, and positive predictive values ranging from 15% to 98%, 38% to 91%,
      and 17% to 30% respectively. Prostitute contact in the past five years would have
      excluded 31% of all donors and 73% of HIV infected donors. 27% of those excluded
      would have been HIV positive. CONCLUSIONS: The widespread assumption that donor
      deferral is not feasible in sub-Saharan Africa needs reassessment. In Abidjan
      this approach was well accepted and potentially effective. Donor deferral
      requires evaluation as a strategy for improving blood safety in resource poor
      areas with high rates of HIV infection.

PMID- 8274920
TI  - Early growth and death from cardiovascular disease in women.
AB  - OBJECTIVE: To determine whether the link suggested between growth in utero and
      during infancy and death from cardiovascular disease in men is also present in
      women. DESIGN: Follow up study of women and men whose birth weight and weight at
      1 year of age had been recorded. SETTING: Hertfordshire, England. SUBJECTS: 5585
      women and 10,141 men born during 1911-30. MAIN OUTCOME MEASURES: Standardised
      mortality ratios for cardiovascular disease. RESULTS: Among women and men death
      rates from cardiovascular disease fell progressively between the low and high
      birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for
      men). Cardiovascular deaths in men but not women were also strongly related to
      weight at 1 year, falling progressively between the low and high weight groups
      (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were
      among those with below average birth weight but above average weight at 1 year.
      In men the highest rates were among those with below average birth weight and
      below average weight at 1 year. CONCLUSION: Relations between cardiovascular
      disease and birth weight are similar in men and women. In men cardiovascular
      disease is also related to weight gain in infancy.

PMID- 8274921
TI  - Growth in utero and serum cholesterol concentrations in adult life.
AB  - OBJECTIVE: To see whether reduced rates of fetal growth are related to raised
      serum cholesterol concentrations in adult life. DESIGN: Follow up study of men
      and women whose size at birth had been recorded. SETTING: Jessop and Northern
      General Hospitals, Sheffield. SUBJECTS: 219 men and women born in the Jessop
      Hospital during 1939-40. MAIN OUTCOME MEASURES: Serum concentrations of total
      cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS:
      Men and women who had had a small abdominal circumference at birth had raised
      serum concentrations of total and low density lipoprotein cholesterol and
      apolipoprotein B. This was independent of the duration of gestation. Serum
      concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval
      0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The
      corresponding figure for serum low density lipoprotein cholesterol was 0.26
      mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07).
      Small head and chest circumferences at birth and short length were each
      associated with raised serum low density lipoprotein cholesterol concentrations
      but the trends disappeared in a simultaneous regression with abdominal
      circumference at birth. The association between abdominal circumference at birth
      and low density lipoprotein cholesterol concentration was independent of social
      class, current body weight, cigarette smoking, and alcohol consumption.
      CONCLUSION: Raised serum cholesterol concentrations in adult life are associated
      with impaired growth during late gestation, when fetal undernutrition has a
      disproportionate effect on liver growth. Impaired liver growth may permanently
      alter low density lipoprotein cholesterol metabolism.

PMID- 8274922
TI  - Reliability of reported family history of myocardial infarction.
AB  - OBJECTIVE: To assess the reliability of reported family histories of myocardial
      infarction. DESIGN: A case-control study in which reported histories of first
      degree relatives were validated from death certificates, general practitioners'
      records, and hospital notes. SETTING: Participants enrolled in the Belfast centre
      of the World Health Organisation's study monitoring trends and determinants in
      cardiovascular disease (MONICA). SUBJECTS: 200 men who survived myocardial
      infarction and 200 age matched controls drawn randomly from the population. MAIN
      OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, and
      proportion of overall agreement with validated records of reported family
      histories of myocardial infarction in first degree relatives; odds ratios for
      myocardial infarction, given at least one reported relative or at least one
      verified relative being affected. RESULTS: 349 of the 400 probands provided
      detailed family histories, reporting on 2812 first degree relatives. The overall
      sensitivity, specificity, and positive predictive value of reported histories
      were 67.3%, 96.5%, and 70.5% for cases and 68.5%, 97.7%, and 73.8% for controls.
      The kappa coefficients were modest: 0.65 for cases and 0.68 for controls. The
      odds ratios for myocardial infarction, given at least one affected relative, were
      not substantially inflated by recall bias. Some recall bias was evident for the
      probands' reports of their siblings' histories of myocardial infarction, the odds
      ratio for a reported history being 1.67 (95% confidence interval 1.09 to 2.57)
      and for the validated history 1.54 (1.01 to 2.37). CONCLUSIONS: Although the
      relative risk of disease is correctly estimated, the predictive accuracy of a
      casual family history of myocardial infarction may limit the effectiveness of
      targeted screening programmes. They may, however, complement other strategies
      based on genetic testing.

PMID- 8274923
TI  - Further follow up of mortality and incidence of cancer in men from the United
      Kingdom who participated in the United Kingdom's atmospheric nuclear weapon tests
      and experimental programmes.
AB  - OBJECTIVES: To study the long term effects of participation in the United
      Kingdom's atmospheric nuclear weapon tests and experimental programmes and to
      test hypotheses generated by an earlier report, including the possibility that
      participation in tests caused small hazards of leukaemia and multiple myeloma.
      DESIGN: Follow up study of mortality and cancer incidence. SUBJECTS: 21,358
      servicemen and civilians from the United Kingdom who participated in the tests
      and a control group of 22,333 non-participants. MAIN OUTCOME MEASURES: Numbers of
      deaths; standardised mortality ratios; relative risks of mortality from all
      causes and 27 types of cancer. RESULTS: During seven further years of follow up
      the numbers of deaths observed in participants were fewer than expected from
      national rates for all causes, all neoplasms, leukaemia, and multiple myeloma
      (standardised mortality ratios 0.86, 0.85, 0.57, and 0.46); death rates were
      lower than in controls (relative risks 0.99, 0.96, 0.57, and 0.57; 90% confidence
      intervals all included 1.00). In the period more than 10 years after the initial
      participation in tests the relative risk of death in participants compared with
      controls was near unity for all causes (relative risk 0.99 (0.95 to 1.04) and all
      neoplasms (0.95 (0.87 to 1.04)); it was raised for bladder cancer (2.69 (1.42 to
      5.20)) and reduced for cancers of the mouth, tongue, and pharynx (0.45 (0.22 to
      0.93)) and for lung cancer (0.85 (0.73 to 0.99)). For leukaemia mortality was
      equal to that expected from national rates but greater than in controls for both
      the whole follow up period (1.75 (1.01 to 3.06)) and the period 2-25 years after
      the tests (3.38 (1.45 to 8.25)). CONCLUSION: Participation in nuclear weapon
      tests had no detectable effect on expectation of life or on subsequent risk of
      developing cancer or other fatal diseases. The excess of leukaemia in
      participants compared with controls seems to be principally due to a chance
      deficit in the controls, but the possibility that participation in the tests may
      have caused a small risk of leukaemia in the early years afterwards cannot be
      ruled out.

PMID- 8274924
TI  - Unemployment rate as predictor of rate of psychiatric admission.
AB  - OBJECTIVE: To examine the relation between rates of psychiatric admissions and
      both the rate of unemployment and the underprivileged area score within small
      areas. DESIGN: Calculation of correlation coefficients and explanatory power by
      using data on psychiatric admissions from April 1990 to March 1992. Crude and age
      standardised rates were used based on all admissions and also on the number of
      people admitted regardless of the number of times each person was admitted.
      SETTING: Sectors with an average population of 45,000 consisting of aggregations
      of neighbouring wards in Bristol and District Health Authority and electoral
      wards with an average population of 9400 in the city of Bristol. RESULTS:
      Unemployment rates explained 93% of the variation in the crude person based
      admission rates standardised for age for those aged under 65 in the sectors.
      Person based rates correlated more strongly with unemployment than did rates
      based on all separate admissions. Inclusion of people aged 65 and over weakened
      the relation. Within electoral wards unemployment rates explained only about 50
      60% of the variation but were still more powerful than the underprivileged area
      score. There was a significant negative correlation between average length of
      stay and readmission rates--that is, sectors with short lengths of stay were more
      likely to have patients readmitted (r = -0.64, 95% confidence interval -0.25 to 
      0.85). CONCLUSIONS: Unemployment rates are an extremely powerful indicator of the
      rates of serious mental illness that will need treatment in hospital in those
      aged under 65. This should be considered in the process of resource allocation,
      particularly to fundholders in general practice, or people with serious mental
      illness living in areas of high unemployment could be considerably disadvantaged.

PMID- 8274925
TI  - Screening migrants at risk of tuberculosis.

PMID- 8274926
TI  - Summary of 1993 World Health Organisation-International Society of Hypertension
      guidelines for the management of mild hypertension. Subcommittee of WHO/ISH Mild
      Hypertension Liaison committee.
AB  - As part of the ongoing process of issuing guidelines for managing hypertension
      the World Health Organisation and International Society of Hypertension present a
      summary of the latest guidelines for the management of mild hypertension. In both
      young and elderly people this condition is a risk factor for cardiovascular
      disease and should be treated. Information is presented on methods of diagnostic
      evaluation and assessment of risk. Methods of treatment, including changes in
      lifestyle, are covered.

PMID- 8274927
TI  - Minimally invasive surgery. Implications for hospitals, health workers, and
      patients.
AB  - Minimally invasive surgery is one of the great innovations of health care in the
      20th century. It promises to revolutionise surgery by allowing many more
      operations to be performed with minimal hospitalisation. Pressure from patients
      has caused many techniques to spread rapidly before they have been adequately
      assessed. This must be resisted, and policy makers must pay more attention to
      minimally invasive surgery to ensure that good assessments are made. The
      widespread use of minimally invasive techniques has important implications for
      hospitals and health workers. As more patients are treated on an outpatient
      basis, fewer hospital beds will be needed, and traditional operating rooms will
      have to adapt to a greater turnover of patients. Surgeons will have to acquire
      new operating skills, possibly requiring formal training and accreditation, and,
      as different specialties fight for control of new technologies, surgery may
      eventually be merged with internal medicine so that specialists will deal with
      organ systems. Postoperative care will have to be carried out in the community
      rather than in hospitals, and policy makers will need to reorganise their health
      systems to cope with these developments.

PMID- 8274928
TI  - Senior house officers: the lost tribes.
AB  - There are more senior house officers than doctors in any other training grade in
      Britain but nobody knows what they do in hospitals or has a clear idea what
      skills they should be learning. Nobody is responsible for them and they suffer
      from having a poor career structure and inadequate training. Now that there are
      government initiatives to reduce the hours that junior doctors work and to limit
      the time it takes to train to become a specialist, the problems that senior house
      officers face can no longer be ignored. A conference for senior house officers
      held last week talked about the problems that they face and tried to find some
      solutions.

PMID- 8274929
TI  - ABC of emergency radiology. Thoracic and lumbar spine.

PMID- 8274930
TI  - Disease of the rotator cuff. Rotator cuff syndrome does not exist.

PMID- 8274931
TI  - Selective decontamination of the digestive tract. Benefit remains unproved.

PMID- 8274932
TI  - Selective decontamination of the digestive tract. Bronchoalveolar lavage valid
      for diagnosing pneumonia.

PMID- 8274933
TI  - Postpartum contraception. Unnecessary before three weeks.

PMID- 8274934
TI  - Market penetration of new drugs. ACE inhibitors prescribed for heart failure.

PMID- 8274935
TI  - Market penetration of new drugs. Compare Britain with other national markets.

PMID- 8274936
TI  - Routine measurement of fibrinogen concentration. Clinically feasible.

PMID- 8274937
TI  - Routine measurement of fibrinogen concentration. Fibrinogen may be just a marker.

PMID- 8274938
TI  - Pain control in children. Guidelines help.

PMID- 8274939
TI  - Pain control in children. Parents underestimate children's pain.

PMID- 8274940
TI  - Underenumeration in 1991 census. Census inaccurate for many ethnic groups.

PMID- 8274941
TI  - Malaria prophylaxis. Mefloquine should be first choice.

PMID- 8274942
TI  - Underenumeration in 1991 census. Forms not retrieved.

PMID- 8274943
TI  - Clinical freedom and drug dependence. Treatment of American was legitimate.

PMID- 8274944
TI  - Undergraduate medical education. Teaching deserves better recognition.

PMID- 8274945
TI  - Undergraduate medical education. Too many facts not enough innovation.

PMID- 8274946
TI  - Undergraduate medical education. Core curriculum should remain flexible.

PMID- 8274947
TI  - Undergraduate medical education. Improve teaching of practical skills.

PMID- 8274948
TI  - Writing wreadable wreports.

PMID- 8274950
TI  - Seven guidelines for testifying in a deposition.

PMID- 8274949
TI  - Computers: questions to ask the vendors.

PMID- 8274951
TI  - Improving ambulatory nursing care.

PMID- 8274952
TI  - Seven steps to simplify charting.

PMID- 8274953
TI  - Indicators for an inpatient psychiatric unit.

PMID- 8274954
TI  - Ten tips for initiating a QIT.

PMID- 8274955
TI  - An analogy to teach quality concepts.

PMID- 8274956
TI  - Nursing quality professionals: what do you need to know?

PMID- 8274957
TI  - The Safe Medical Devices Act: what it means in practice.

PMID- 8274958
TI  - Writing valid and reliable indicators.

PMID- 8274959
TI  - Primary care: moving from QA to QI.

PMID- 8274960
TI  - Hints for carrying out action plans.

PMID- 8274961
TI  - Applying the AHCPR guideline.

PMID- 8274962
TI  - QI tools. Pareto charts.

PMID- 8274963
TI  - Improving documentation: three ways.

PMID- 8274964
TI  - The use of a digitizer to measure area in dermatology.
AB  - The accuracy and reproducibility of area measurements made with a computerized
      digitizer were studied. Known areas were measured varying the way in which the
      system was operated, altering the characteristics of the shapes being measured
      and varying the ways in which the image on the computer screen was formed.
      Accuracy and reproducibility were dependent on all these factors; altering the
      operating technique caused the mean measured area to vary from 76% to 124% of the
      actual area, with the greatest inaccuracies being produced by altering the
      computer screen image. The accuracy and reproducibility of results obtained using
      a digitizer are critically dependent on the way in which it is used.

PMID- 8274965
TI  - A model of the instantaneous pressure-velocity relationships of the neonatal
      cerebral circulation.
AB  - The instantaneous relationship between arterial blood pressure (BP) and cerebral
      blood flow velocity (CBFV), measured with Doppler ultrasound in the anterior
      cerebral artery, is represented by a vascular waterfall model comprising vascular
      resistance, compliance, and critical closing pressure. One min recordings
      obtained from 61 low birth weight newborns were fitted to the model using a least
      squares procedures with correction for the time delay between the BP and CBFV
      signals. A sensitivity analysis was performed to study the effects of low-pass
      filtering (LPF), cutoff frequency, and noise on the estimated parameters of the
      model. Results indicate excellent fitting of the model (F-test, p < 0.0001) when
      the BP and CBFV signals are LPF at 7.5 Hz. Reconstructed CBFV waveforms using the
      BP signal and the model parameters have a mean correlation coefficient of 0.94
      with the measured flow velocity tracing (N = 232 epochs). The model developed can
      be useful for interpreting clinical findings and as a framework for research into
      cerebral autoregulation.

PMID- 8274966
TI  - Bandwidths of respiratory gas flow and pressure waveforms in mechanically
      ventilated infants.
AB  - The frequency content of airway pressure and gas flow in mechanically ventilated
      infants (MVIS) has not been adequately investigated. Pressure-cycled infant
      ventilators generate pressure pulses with short rise-times. Gas flow is
      approximately equal to the derivative of pressure when lung compliance is low,
      and hence contains high-frequency components. We defined bandwidth as that
      frequency fm below which 99.9% of the energy of the signal resided. Simulation of
      the measurement process using measurement systems with frequency response similar
      to sixth-order Bessel filters and a lung model comprising series resistance,
      inertance and compliance showed that measurement systems with frequency response
      flat +/- 10% to fm yield time domain errors less than 3% of the peak value. We
      digitized pressure and flow signals from 10-20 ventilator (Healthdyne 105)
      breaths in 33 stable MVIS. The transducers' (Gould P50, Hans Rudolph 8300 screen
      pneumotach) frequency responses had been measured between 1 Hz and 100 Hz and
      phase matched at 10 Hz. We calculated total respiratory resistance R and
      elastance E using multiple linear regression, and ensemble-average power spectral
      density using the FFT with a rectangular time window and padding to 2048 points.
      Power spectra were compensated for non-unity transducer and anti-alias filter
      responses up to 60 Hz. Measured data sequences that were not self-windowing due
      to spontaneous breathing efforts, that yielded regression R2 < 0.95 or that
      contained flow oscillations due to secretions in the airway were discarded.
      Satisfactory results were obtained from more than eight breaths in 18 infants.
      Mean bandwidths (+/- SD) of pressure and flow waveforms were 4.7 +/- 0.7, range
      3.5-5.9 and 19.6 +/- 6.5, range 10.8-32.1 Hz, respectively. Flow bandwidths B
      correlated with the respiratory time constant tau (B = -77.2 tau + 26.8, R2 =
      0.55, P < 0.0002), and with elastance E (B = 61.4E + 10.1, R2 = 0.74, P <
      0.0001). We conclude that the bandwidth of the flow waveform increases with
      decreasing compliance and mechanical time constant. The frequency response of
      pressure and flow measurement systems should be flat +/- 10% at least up to 6 and
      32 Hz respectively to obtain data with dynamic errors less than 3% in infants
      with low-compliance lung disease.

PMID- 8274967
TI  - Nocturnal end-tidal PCO2 to detect apnoeas and hypopnoeas in sleep-disordered
      breathing.
AB  - In this study, the end-tidal PCO2 (PETCO2) during the night was measured. The
      PETCO2 signal was obtained by introducing a cannula through the nose into the
      nasopharyngeal cavity. The usefulness of this method to identify nocturnal
      hypoventilation was studied in 29 patients with chronic obstructive pulmonary
      disease (COPD) with and without oxygen supplementation. The results showed that
      27 patients with COPD developed 67 nocturnal oxygen desaturations which were all
      accompanied by raised PETCO2. During oxygen therapy in all COPD patients
      nocturnal episodes with increased PETCO2 occurred. Furthermore, the detection of
      nocturnal apnoeas and hypopnoeas was assessed in 19 subjects who were referred to
      the sleep laboratory for snoring and daytime sleepiness. In this group episodes
      of disordered breathing could easily be assessed. The PETCO2 signal was
      especially useful to identify hypopnoeas that were accompanied by only small dips
      in SaO2 (< 3%). It is concluded that PETCO2 measurement is useful in the
      detection of hypoventilation during sleep in COPD patients, especially when they
      receive supplemental oxygen. PETCO2 recording detects obstructive apnoeas and
      hypopnoeas and is especially helpful to identify hypopnoeas which are accompanied
      by only small dips in oxygen saturation.

PMID- 8274968
TI  - Use of the frequency-tracking locus in estimating the degree of respiratory
      entrainment in preterm infants.
AB  - In order to define the complex interactions between external stimuli and non
      linear physiological systems, a technique (the frequency-tracking locus, FTL) was
      devised that describes the cycle-by-cycle changes in phase angle and amplitude
      between two signals. Qualitative assessment of the nature of interactions between
      the signals can be made by examining the FTL. Quantitation of the extent of
      entrainment of the spontaneous physiological rhythm is possible after deriving a
      numerical index (the path-length index, PLI) describing the departure of the
      system from a fully entrained state. The FTL was applied to the study of
      interactions between spontaneous respiratory effort and mechanical inflation in
      preterm newborn babies undergoing mechanical ventilation. Stable and unstable
      states of 1:1 interaction were noted while integer-ratio relationships were seen
      at low rates of mechanical ventilation. Stable states of entrainment corresponded
      to a PLI value near unity, and the value of PLI increased rapidly as interactions
      became unstable. The FTL may be used to describe complex interactions in
      physiological systems, and may be used as a guide to baby-ventilator matching
      during mechanical ventilation of the newborn.

PMID- 8274969
TI  - Can bio-electrical impedance be used to measure total body water in dialysis
      patients?
AB  - The measurement of total body water (TBW) by bio-electrical impedance (BEI) in a
      group of renal patients was evaluated against the tritium dilution method. The
      effect of haemodialysis and the presence of peritoneal dialysate on the impedance
      were also investigated. The correlation between the two methods was r = 0.9, with
      the standard deviation of the differences being 3.66 l (TBW typically 40 l). The
      BEI method overestimated the actual weight loss after haemodialysis, but
      underestimated the volume of peritoneal dialysate in situ. The BEI method would
      not be appropriate for use in assessing total body water and monitoring acute
      volume changes in patients with renal failure who are on strict fluid
      restriction.

PMID- 8274970
TI  - Contactless impedance measurement by magnetic induction--a possible method for
      investigation of brain impedance.
AB  - Using a primary coil that induces eddy currents in a volume conductor, and a pair
      of secondary coils configured to form a differential transformer, it is possible
      to measure the conductivity of a volume conductor by the magnetic fields of the
      induced eddy currents. This method is especially favourable for measuring
      impedance of the brain, as the low conductance of the surrounding skull
      interferes only very slightly with the measuring process. In a simulation
      experiment a life-size skull model was filled with NaCl solutions of different
      concentrations in each half, so as to model the impedances of a normal and an
      oedematous hemisphere. The impedance differences could be clearly detected by a
      coil system of 25 mm diameter.

PMID- 8274971
TI  - A comparison of four commercial systems used to measure whole-body electrical
      impedance.
AB  - Four commercial whole-body impedance measuring systems (Holtain, RJL, Bodystat
      and EZcomp) were compared on two separate occasions for a group of normal
      subjects. The first set of readings in 21 subjects demonstrated a significant
      difference of approximately 6% between the Holtain measurement and the higher
      readings from the Bodystat or RJL systems. The differences between the RJL and
      Bodystat readings were much less (mean difference 0.6%). Similar differences
      between the Holtain and EZcomp or Bodystat measurements were demonstrated on a
      second occasion for a group of 11 subjects. Given that these devices operate by
      supplying a constant current, the differences may be explained by the results
      from a series of measurements on a whole-body resistance simulator in which it
      appears that for skin contact resistance > 200 omega the Holtain device is unable
      to sustain a constant current and therefore records a lower impedance than the
      true value.

PMID- 8274972
TI  - An experimental single-sideband acoustical re-injection test method for Doppler
      systems.
AB  - An experimental acoustical re-injection system based on a wideband single
      sideband generator has been developed. This has been used to present a clinical
      Doppler system with a simulated Doppler shift, as would be obtained from a
      unidirectional moving reflector. Development of this approach should permit
      independent electronic testing of forward and reverse channels, including mean
      and peak frequency calculations and measurement of channel separation. Sideband
      suppression of 28 dB minimum has been obtained for a range of ultrasound
      frequencies from 2.5 MHz to 10 MHz and audio frequency shifts up to 10 kHz.

PMID- 8274973
TI  - Arterial closing or re-opening pressure?

PMID- 8274974
TI  - Neuromagnetism: theory, technology and applications. Workshop, 25-28 October
      1990, Erlangen, Germany. Proceedings.

PMID- 8274975
TI  - A comparison of different numerical methods for solving the forward problem in
      EEG and MEG.
AB  - In view of the complexity of the conductivity and the geometry of the human head,
      a numerical method would appear to be necessary for the adequate calculation of
      the electric potential and the magnetic induction generated by electric sources
      within the brain. Four numerical methods that could be used for solving this
      problem are the finite-difference method, the finite-element method, the boundary
      element method, and the finite-volume method. These methods could be used to
      calculate the electric potential and the magnetic induction directly.
      Alternatively, they could be applied to the electric potential or the electric
      field and the magnetic induction could then be determined by numerical
      integration of the Biot-Savart law. In this paper the four numerical methods are
      briefly reviewed. Thereafter the relative merits of the methods and the various
      options for using them to solve the EEG and MEG problem are evaluated.

PMID- 8274976
TI  - The MEG in evaluation of generalized epilepsy.
AB  - This review looks at the magnetoencephalogram (MEG) studies on generalized
      epilepsy starting from the first cases investigated up to the most recent
      contributions regarding the photoconvulsive response and the results obtained
      applying the template analysis. As far as the spike-and-wave complex is
      concerned, in the cases both of photoconvulsive response and of non-generalized
      epilepsy, a primary multiregional participation of the cerebral cortex is shown,
      which, variable in time and often with a side prevalence, is alternated by
      bisynchronous epileptiform activity starting from midline structures.

PMID- 8274977
TI  - Multichannel magneto-electroencephalography recordings of interictal and ictal
      activity.
AB  - A lobar or even a intralobar congruence was found when comparing the findings of
      magnetic source localization with presurgical evaluation (EEG, MRI and
      intraoperative ECoG) in temporal lobe epilepsy. The first dipolar activity that
      can be recognized during a spike-wave event (primary focal epileptic activity
      (PFA)) was localized in temporal neocortical or mesial regions. Further centres
      of epileptic activity could be localized by the method of spike averaging by
      correlation. This was interpreted as propagation of the electric activity. The
      comparison of interictal and ictal MEG localization results showed congruency in
      a patient with temporal lobe epilepsy. The combination of MEG and MRI helps to
      build a bridge between morphological and functional localization. MEG can serve
      as a pointer to discrete lesions in MRI.

PMID- 8274978
TI  - Identification of discrete regions of activity using correlation coefficient
      scanning of distributed current maps.
AB  - Biomagnetic measurements of the brain are often analysed in terms of a number of
      discrete primary generators. In this paper we describe an objective method of
      identifying the number of approximate location of such generators. The method is
      based on the matching of an instrument-independent representation of the data
      with a template whose pattern is characteristic of a localized primary source.
      The method is shown to be insensitive to severe noise and to be capable of
      resolving closely spaced generators.

PMID- 8274979
TI  - Sources of electric brain activity: intracortical current dipoles.
AB  - Intracortical evoked potentials after electrical stimulation of the optic nerve
      were simultaneously recorded from the different layers of the rabbit's visual
      cortex. The averaged potentials were subjected to current source density
      analyses. The results show that the first event after the stimulus is a current
      sink in layer VI according to the excitatory terminations of the specific
      afferent fibres of the geniculate body. Since the largest part of the specific
      afferents terminates in layers IV and V, the sink in those layers may be due to
      excitatory synaptic events there. The corresponding current sources are situated
      in the upper layers and are most probably passive sources due to the active
      sinks. This example demonstrates that the generation of intracortical electric
      potentials can be explained by vertically oriented current dipoles according to
      the anatomical peculiarities.

PMID- 8274980
TI  - Localization of sources of brain alpha/theta/delta activity and the influence of
      the mode of spontaneous mentation.
AB  - A method is described that accounts for multichannel brain field data (EEG)
      epochs, after transformation into the frequency domain, by a single oscillating
      dipole source in terms of phase angles. The method produces a potential
      distribution for each frequency point ('FFT dipole approximation'). These maps
      can be subjected to conventional equivalent dipole source fittings in terms of
      amplitudes. We studied the equivalent source locations for the different temporal
      EEG frequency bands (delta/theta/alpha) in 12 normal subjects during the
      collection of reports of spontaneous thoughts. Some of the thought reports were
      classed into two modes, 'visual imagery' and 'abstract', and the associated
      equivalent source locations during the 2 s immediately prior to these reports
      were computed. Different equivalent source locations were found for the different
      spectral components of the EEG, implying that different neural generator
      populations generate the different frequencies. Further, the different types of
      spontaneous thought, i.e. different modes of cortical functioning, were found to
      be associated with the activity of different neuronal generator sources that
      operated at the same frequency at different source locations.

PMID- 8274981
TI  - Separation of sources of neuromagnetic examinations.
AB  - Phantom experiments and computer simulations in combination with the Wiener
      Helstrom filter reconstruction technique demonstrate the ability of the
      improvement of source separation in distributed current arrangements. A spatial
      region of interest (ROI), in which the current distribution is expected, is
      defined and discretized into three-dimensional voxel elements. Inside the ROI the
      number and spatial extension of the current sources are determined by
      reconstructing the impressed current density distribution separately from volume
      conductor effects. The volume currents can be determined depending on the actual
      head shape and the location of the ROI using finite difference methods before the
      reconstruction of the impressed current density. As a result the reconstruction
      procedure is very fast. Without a priori information about the number of active
      generators and the spatial extension inside the ROI, the method improves the
      separation of simultaneously active sources and distributed sources in comparison
      with the reconstruction of the total current density. However, with increasing
      depth of the sources (deeper than 5-6 cm) the intrinsic smoothing properties of
      the inverse magnetic problem prevent the separation. The resolution is better in
      the case of distributed sources in comparison with multiple point-like
      generators.

PMID- 8274982
TI  - Somatosensory evoked potentials and magnetic fields: separation of multiple
      source activities.
AB  - Median nerve somatosensory evoked potentials (SEP) and magnetic fields (SEF) were
      recorded in two subjects with multichannel (32 SEP, 24 SEF channels) devices in
      Aachen and Helsinki. Single-moving- and multiple-stationary-dipole models were
      compared with the brain electric source analysis (BESA) program of Scherg.
      Subcortical sources, reflecting the afferent neural volley when entering the
      brainstem and leaving the thalamus, were found only in the SEP. The analysis of
      SEF and SEP revealed a minimum of four overlapping source activities in the
      region of the contralateral post-and precentral cortical projection areas. Two
      sources in the depth of the central sulcus could not be resolved unambiguously.
      The third, more superficial source, which probably reflects activation of area 1,
      was better defined in the source analysis of the SEP, because dipole orientation
      was close to radial. The fourth source was more posterior. Its initial activity
      around 30 ms was seen consistently in SEP and SEF. Several problems observed in
      the analysis of the present MEG and EEG data suggest that the simultaneous
      measurement and analysis of multichannel EEG and MEG data will substantially
      increase spatio-temporal resolution.

PMID- 8274983
TI  - The dipole density plot (DDP), a technique to show concentrations of dipoles.
AB  - To analyse spontaneous multichannel slow-wave MEG activity a tool was developed
      to extract focal abnormal activity with a higher spatial dipole density across
      time. The first version works on discrete volume units, the second version avoids
      a possible location error, works continuously and can be adjusted for individual
      slices three-dimensionally. The first version is used for screening and the
      second version is used to go into more detail. The dipole density plot (DDP) is
      not limited to single foci, nor to the single-dipole model; neither is it limited
      to the MEG. The DDP seems to be a valuable tool for detecting and locating
      lesions three-dimensionally within the brain.

PMID- 8274984
TI  - First experiences with a multichannel software gradiometer recording normal and
      tangential components of MEG.
AB  - We describe a 28-channel magnetometer that operates as a 22-channel 'software
      gradiometer'. Gradiometer function is achieved by subtraction of weighted signals
      representing the noise field along three orthogonal axes as detected by six
      compensation channels. The instrument measures both normal and tangential field
      components; the user can select a total of 22 normal and/or tangential measuring
      sites from two arrays of 16 sites each. First experiences indicate that the
      combination of a shielded room with a software suppression of the residual field
      entering the room is amply sufficient to allow biomagnetic measurements in a
      hospital environment.

PMID- 8274985
TI  - Auditory evoked magnetic fields in stroke.
AB  - Auditory magnetic fields evoked by noise/square-wave sequences, presented once
      every 2.2 s, were recorded in eight subjects who had had a stroke in the auditory
      cortex or in its vicinity. In two subjects with large temporoparietal lesions,
      the magnetic 100 ms deflection (N100m) was absent over the damaged side. In one
      subject with a large but less deep temporoparietal lesion, a small N100m could be
      discerned on the defective side. The latency of N100m was increased in patients
      with frontal lesions. Small damages in the vicinity of the supratemporal plane
      had no effect on N100m. Magnetoencephalography is particularly applicable to
      outpatient studies of stroke.

PMID- 8274986
TI  - Experience with a multichannel system for biomagnetic study.
AB  - The components of the biomagnetic multichannel system Krenikon are described. The
      combination of biomagnetically yielded localizations with anatomic images gained
      from MR or CT is discussed as well as the enhancement of the signal-to-noise
      ratio by using a correlation technique. The overall localization accuracy is
      tested with technical phantoms. With volunteers measurements of auditory, visual
      and somatosensory evoked fields are performed to evaluate the system performance
      in vivo. Clinical studies were performed mainly with partners from the
      Universities of Erlangen-Nunberg and Ulm. The data acquisition time typically is
      2-10 min which is tolerable both for the patient and the clinical staff. Electric
      potentials even with invasive electrodes can be recorded simultaneously with the
      magnetic fields. MEG gives important information for the presurgical diagnosis of
      epileptic patients and for the understanding of the epilepsy genesis. With MCG,
      centres of biologic excitation such as ventricular ectopies or accessory bundles
      in WPW syndrome have been successfully localized.

PMID- 8274987
TI  - Magnetocardiography: clinical investigations with a biomagnetic multichannel
      system.
AB  - The magnetic fields caused by the human heart's electrical activity were
      simultaneously recorded with a multichannel superconducting quantum interference
      device (SQUID) system (Krenikon) for 1-10 min in 45 patients. 31-37 magnetic
      channels were recorded simultaneously with the electrocardiogram (ECG) and
      respiration. Comparison of a magnetic index and the Sokolow-Lyon index with
      echocardiographic findings in the quantification of left ventricular hypertrophy
      demonstrated the superiority of the magnetocardiogram (MCG) as compared with the
      ECG. The magnetocardiographic investigation of patients with Wolff-Parkinson
      White (WPW) syndrome, ventricular extrasystoles, ventricular tachycardia, and
      paced ventricular arrhythmias demonstrated that multichannel magnetocardiography
      permits the non-invasive three-dimensional localization of arrhythmogenic tissue
      with high spatial accuracy.

PMID- 8274988
TI  - Auditory evoked magnetic fields: analysis of the N100/P200 signal.
AB  - We propose a method to analyse the N100/P200 structure observed in auditory
      evoked magnetic fields. Based in linear cable theory for passive dendritic
      conduction we assume an expression for the time-course of the equivalent current
      dipole moment and show that good agreement can be obtained with experimental
      results. The analysis leads to realistic values for the membrane time constant
      (approximately 30 ms) and the reduced dendritic length (approximately 2).

PMID- 8274989
TI  - Brain function as revealed by current density analysis of magnetoencephalography
      signals.
AB  - Magnetoencephalography signals are used to extract two-dimensional estimates of
      the cortical current density associated with spontaneous and steady state brain
      activity as well as auditory and visual evoked responses. The results provide
      clues about the organization of the electrical activity across wide cortical
      regions. Similarities and differences in spontaneous and evoked responses are
      highlighted and related to findings from other techniques, raising the
      possibility that volume conduction currents may play some role in coordinating
      brain function across widely separated cortical regions.

PMID- 8274990
TI  - Auditory magnetic fields in cochlear-implant patients.
AB  - Neuromagnetic recordings were used to check if electrical stimulation of the
      auditory nerve in cochlear-implant patients activates cortical auditory areas in
      a similar manner as acoustic stimulation in normal hearing subjects or whether
      the excitation processes are different. The waveform of the evoked magnetic field
      complex elicited by electrical stimulation of the auditory nerve as well as the
      distribution of the magnetic responses over the head resemble that of auditory
      evoked fields elicited by acoustic stimulation of normal subjects. The location
      and direction of the equivalent dipole are consistent with activation of the
      auditory cortex. Neuromagnetic recordings could be used in the future (i) to
      check activation of the auditory cortices in cochlear-implant patients; (ii) to
      gather information about the functional properties of this activity, and (iii) to
      study the integrity of central auditory pathways in totally deaf patients.

PMID- 8274991
TI  - Multichannel magnetic recording of P300 activity.
AB  - The magnetic correlate of the P300 wave was registered using a seven-channel
      detector. The spatial variation of the corresponding field suggests the
      contribution of outer brain layers to the neural activity of M300.

PMID- 8274992
TI  - Nerve, plexus and spinal cord: possible targets for non-invasive neuromagnetic
      measurements in man.
AB  - Somatosensory evoked neuromagnetic fields are recorded from peripheral nerves in
      the upper arm, from plexus brachialis at the ventral and dorsal thorax and from
      the dorsal horn of the cervical spinal cord ('P13m') at the upper lateral neck.
      Some perspectives for clinical applications are suggested.

PMID- 8274993
TI  - Electrical source analysis by brain mapping techniques.
AB  - Brain EEG mapping techniques are employed in our department as a preliminary
      device for the selection of patient tributaries for more complex
      neurophysiological techniques: EEG combined with video-filming, foramen ovale
      electrodes, depth and subdural electrodes etc. Different methods of brain EEG
      mapping may be employed for the localization of the origin of epileptic
      discharges: power maps based on a FFT method; power maps based on instantaneous
      EEG amplitude; and in the last few years, new dipole programs working with the
      dipole localization method, the so-called 'inverse solution', that indicates the
      existence of one or more dipoles as sources of discharges, and their localization
      in a coordinate axis oriented in the three space directions. Brain EEG mapping
      has the advantage of low cost, but its main inconvenience is the relatively low
      level of accuracy in the localization of the sources. Neuromagnetic techniques
      give the best level of accuracy in source localization, but their cost is very
      high. The final considerations would be how much neuromagnetic techniques improve
      the results obtained by brain mapping techniques, and the specific areas where
      these techniques should be assigned.

PMID- 8274994
TI  - MEG and EEG in epilepsy: is there a difference?
AB  - Interictal epileptiform activity recorded by scalp EEG, foramen ovale electrodes
      and MEG is discussed. Gross differences in waveform between the electric and
      magnetic records are discussed in the light of intracranial depth recordings.

PMID- 8274995
TI  - Redesigning needs assessment for new JCAHO standards.

PMID- 8274996
TI  - Self-directed learning: teaching by testing.

PMID- 8274997
TI  - Joy in your job.

PMID- 8274998
TI  - Tips for applying TQM in shared governance settings.

PMID- 8275000
TI  - Fun teaching strategies for medical terminology.

PMID- 8275001
TI  - Competencies for staff development.

PMID- 8274999
TI  - Coaching staff to write exemplars or nursing narratives.

PMID- 8275002
TI  - Take N.O.T.E.S.--a business education partnership.

PMID- 8275003
TI  - Does your organization have a learning disability.

PMID- 8275004
TI  - Competency validation: are you in the line of fire?

PMID- 8275005
TI  - Interdisciplinary education solves a utilization review problem.

PMID- 8275006
TI  - Survey nightmares.

PMID- 8275007
TI  - Tips for choosing a consultants.

PMID- 8275008
TI  - Revisiting old change theories.

PMID- 8275009
TI  - [Determination of the melanin level in human melanosomes in the pigment
      epithelium of the eye depending on age].

PMID- 8275010
TI  - Isolation and characterization of laminin binding protein from regenerating rat
      liver plasma membrane.
AB  - Interaction of rat hepatocytes with laminin, the major basement membrane adhesive
      glycoprotein was studied. Rat fetal hepatocytes attached more to laminin than
      adult hepatocytes. Laminin promoted attachment of fetal hepatocytes in a
      concentration dependent manner and showed saturable binding pattern. Hepatocytes
      from CCl4 induced regenerating rat liver also attached more to laminin. The
      pentapeptide YIGSR derived from laminin promoted attachment of adult and fetal
      hepatocytes, but to a lesser extent. A 67 kDa protein was isolated from the
      hepatic plasma membrane of CCl4 induced regenerating rat liver by affinity
      chromatography over laminin sepharose. This protein appeared to be relatively
      abundant in regenerating liver than in normal liver. The radioiodinated 67 kDa
      protein could be inserted into liposomes and these liposomes attached to
      coverslips coated with laminin in a concentration dependent manner in a divalent
      cation free medium. Its specificity for laminin was also revealed by absence of
      significant binding to fibronectin and collagen.

PMID- 8275011
TI  - Effects of prolactin and androgens on enzymes of carbohydrate metabolism in
      seminal vesicles of castrated mature bonnet monkeys, Macaca radiata.
AB  - Effects of prolactin(Prl), bromocriptine(Br), testosterone propionate (TP),
      dihydrotestosterone (DHT) and combinations of these androgens with Prl/Br on the
      maximum catalytic capacities of seminal vesicular enzymes involved in the
      glycolytic and pentose phosphate pathways in castrated mature monkeys were
      studied. Castration decreased the activities of all of the enzymes studied such
      as hexokinase(HK), 6-phosphofructokinase(PFK), glyceraldehyde-3-phosphate
      dehydrogenase(G3PD), pyruvate kinase(PK), glucose 6-phosphate dehydrogenase
      (G6PD) and 6-phosphogluconate dehydrogenase(6PGD) in the seminal vesicles. Prl
      restored the activities of all of the enzymes to their normal values except G3PD.
      TP/DHT maintained all the enzyme activities at the normal tissue intact level.
      Prl given along with androgens further enhanced the androgen action with regard
      to all the enzymes activities except G3PD. Br decreased all of the enzymes but Br
      with androgens maintained all the enzyme activities at the normal level.
      Castration decreased significantly serum T/DHT titres but Prl did not alter Prl
      levels. Prl+TP/DHT elevated Prl levels. Br alone decreased serum Prl, T and DHT
      titres, but Br+TP/DHT decreased only Prl, elevated T and maintained DHT levels.
      These results suggest that Prl has a direct as well as a synergistic action with
      androgens on the activities of the enzymes of glycolysis and pentose phosphate
      pathways in the seminal vesicles of castrated monkeys.

PMID- 8275012
TI  - Degradation of the arginyl-tRNA synthetase protein during purification by
      affinity chromatography on immobilized total tRNA and immobilized tRNA, specific
      for arginyl-tRNA synthetase.
AB  - Arginyl-tRNA synthetase was prepared from Bom:NMRI mouse liver postribosomal
      supernatants. Purification was performed by either gel filtration on Sephadex G
      200 or chromatofocusing before affinity chromatography on immobilized total tRNA
      (mixture of tRNA's, specific for all aminoacyl-tRNA synthetases), followed by
      affinity chromatography on immobilized tRNA, specific for arginyl-tRNA
      synthetase. The purification factor for arginyl-tRNA synthetase activity was
      16700x. Following sodium dodecyl sulphate polyacrylamide electrophoresis several
      protein bands were found in the purified material. All these protein bands were
      shown to possess arginyl-tRNA synthetase activity.

PMID- 8275013
TI  - Autophosphorylation of degradation products of arginyl-tRNA synthetase protein,
      isolated from Bom:NMRI mouse liver.
AB  - Proteins of M(r) 140, 60, 57, 50, 22, and 14 kDa, all possessing arginyl-tRNA
      synthetase activity, were subjected to phosphorylation without addition of
      exogenous protein kinase activity. All proteins except the 14 kDa were shown to
      contain endogenous protein kinase activity. The product of autophosphorylation of
      the 60, 57, 50, and 22 kDa proteins was identified as a phosphorylated 14.9 kDa
      molecule. In some cases higher molecular weight phosphorylated proteins were also
      detected. Properties of the 60 kDa species are described.

PMID- 8275014
TI  - Molecular activation of a trehalase purified from the fat body of a coleopteran
      insect (Tenebrio molitor), by an endogenous insulin-like peptide.
AB  - Trehalase is the major factor involved in the release of glucose in the various
      insects organs. During physiological regulatory processes, and particularly
      during the induction or breaking of diapause, insulin-like factors are involved.
      Then, by contrast with the classical hypoglycemic role of insulin, the insulin
      like peptide isolated from the insect (brain and/or fat body) is also able to
      activate the fat body trehalase in vitro, through a direct molecular interaction.
      The mechanism involves the binding of the activator to the "trehalase-trehalose
      complex", rather than on the free enzyme, without change in the Hill coefficient
      nor in the maximum velocity (Vmax). The rate constant KR is conversely
      proportional to the activator concentration. This mechanism can be totally
      quenched by adding an anti-serum anti-insulin-like factor in the reaction medium.

PMID- 8275015
TI  - Studies of biochemical changes in cultured skin fibroblasts derived from sporadic
      and familial Alzheimer's disease individuals: qualitative and quantitative
      changes in double-stranded DNA-stimulated phosphorylation of endogenous
      nucleoproteins.
AB  - Endogenous proteins phosphorylated in vitro with nuclear extracts prepared from
      skin fibroblasts of familial and sporadic AD subjects and age/sex-matched
      controls show qualitative/quantitative changes which were dependent upon the
      addition of natural and synthetic double-stranded DNA (dsDNA) to assay mixtures.
      Control and AD cell-free homogenates showed a pronounced increase in four
      proteins migrating with molecular weights of 180- (p180), 75-(p75), 65- (p65),
      and 34-kD (p34). Optimal stimulation of each protein required a different
      concentration of dsDNA. In AD samples, an additional dsDNA-stimulated protein,
      p40, was observed. In extracts prepared from sporadic AD individuals, synthetic
      dsDNA stimulated the phosphorylation of two additional proteins, with molecular
      weights of 73- and 37-kD, which were not found in familial AD or control samples.
      These results suggest that dsDNA-stimulated phosphoprotein changes may be used to
      distinguish between familial and sporadic forms of AD.

PMID- 8275016
TI  - A mechanism of vitamin E-enhanced active oxygen formation in concanavalin A
      stimulated alveolar macrophage.
AB  - Vitamin E had an enhancing effect on active oxygen generation in concanavalin A
      (Con A)-stimulated alveolar macrophages (AMs) of rats. An inhibitor against
      protein kinase C (PKC) 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7)
      suppressed a large part of this vitamin E-related effect, but a calmodulin
      antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) did not
      inhibit the increase of active oxygen formation by vitamin E treatment. These
      results suggest that the activation of PKC presumably relates to the enhancing
      effect of vitamin E on active oxygen formation in Con A-stimulated AMs.

PMID- 8275017
TI  - Increased oxidative stress in the liver of mice treated with trichloroethylene.
AB  - In this study the trichloroethylene treatment-associated production of oxidative
      stress in mouse liver by measurements of changes in oxygen consumption, the
      disappearance of beta-nicotinamide adenine dinucleotide reduced form (NADPH), and
      the rate of malondialdehyde formation have been investigated. The treatment of
      mice with trichloroethylene (TCE), trichloroacetic acid (TCA), a metabolite of
      TCE, or clofibrate, a peroxisome proliferator, resulted in an increase in the
      oxygen consumption of liver microsomes compared to the values of the untreated
      controls. A maximum increase in the level of oxygen consumption in liver
      microsomes was observed in the mice treated with TCE, followed by clofibrate and
      TCA treatments. All three agents also increased the rate of NADPH oxidation in
      mice liver microsomes compared with untreated controls. NADPH oxidation was
      increased four fold by TCE or clofibrate (38 or 37 nmol/min) and two fold by TCA
      treatment (17 nmol/min) over that of the control animals (9 nmol/min). The
      concentration of malondialdehyde was higher in all three treated groups in
      comparison with control values. Malondialdehyde levels were elevated by 227%,
      191%, and 118% by treatment with TCE, clofibrate, and TCA, respectively.
      Increases in the levels of oxygen consumption, NADPH disappearance, and
      malondialdehyde production in microsomes from liver of mice treated chronically
      with TCE or TCA are all indicative of elevated levels of oxidative stress.
      Increased oxidative stress may be involved in the induction of TCE-associated
      hepatotoxicity.

PMID- 8275018
TI  - Synthesis and distribution of rat Sertoli cell proteoglycans are modulated by
      linoleate and vitamin E.
AB  - In rat Sertoli cells, linoleate addition modified cell membrane fatty acid
      composition and changes depended on linoleate concentrations. In presence of the
      lowest 18:2 n-6 concentrations (2.5 and 7.5 microM), decrease in proteoglycan
      synthesis paralleled increase in n-6 linoleate-derived metabolites. At high
      concentration (21 microM), linoleate accumulated in membranes and level of n-6
      linoleate-derived metabolites returned to basal value, without change in
      proteoglycan synthesis. Linoleate modified proteoglycan distribution in Sertoli
      cells by an increase in peripheral proteoglycans and a concomitant decrease in
      medium proteoglycans. Vitamin E (100 microM) did not alter fatty acid composition
      in control and linoleate-treated cells, but enhanced proteoglycan production.
      Furthermore, this agent counteracted linoleate-induced modifications in
      proteoglycan cell distribution.

PMID- 8275019
TI  - Interaction of cholesterol containing liposomes with blood serum lipoproteins.
AB  - The interaction of liposomes containing different amounts of cholesterol with
      human serum low density lipoproteins was investigated. Efficiency of the
      interaction depended on the cholesterol content of liposomes and was highest for
      liposomes with the maximal cholesterol/phospholipid molar ratio. The latter
      selectively and effectively interacted with low density lipoproteins, with up to
      90% of lipoprotein particles interacting with liposomes in serum. Fusion of the
      particles with liposomes was observed during the interaction.

PMID- 8275020
TI  - Fumarate catabolism in Helicobacter pylori.
AB  - The metabolism of fumarate by Helicobacter pylori was investigated employing one-
      and two-dimensional 1H and 13C nuclear magnetic resonance spectroscopy.
      Metabolically competent cells generated malate and succinate from fumarate as the
      sole substrate indicating the presence of fumarase and fumarate reductase
      activities in the bacterium. In incubations of fumarate with cell lysates
      accumulation of lactate, acetate, formate and alanine was observed after the
      initial production of malate and succinate. The results indicate the existence of
      active fumarate catabolism in H. pylori and suggest the possibility of an ATP
      generating mechanism which may play an important role in the bioenergetics of the
      bacterium.

PMID- 8275021
TI  - Isolation and characterization of siderophores and envelope proteins from
      mycobacteria.
AB  - Mycobacteria produce two types of siderophores, the exochelins and the
      mycobactins under iron-starved conditions. Attempts were initiated to separate
      the exochelins and mycobactins isolated from four strains of mycobacteria grown
      under iron-deficient conditions by chromatographic procedures. The expression of
      iron-regulated envelope proteins were also studied. Autoradiography of exochelins
      labelled with 55Fe indicates that three M. tuberculosis strains produce similar
      kinds of exochelins but they are different from the exochelins produced by M.
      Smegmatis. The mycobactins from the three M.tuberculosis strains are identical
      but they are different from the mycobactins produced by M. Smegmatis. SDS-PAGE
      electrophoresis of membrane and cell-wall fractions from four strains of
      mycobacteria revealed a number of proteins under iron-deficient conditions.

PMID- 8275022
TI  - Effect of iron on the growth and siderophore production of mycobacteria.
AB  - To gain a better understanding of the role of iron in the pathogenesis of
      tuberculosis, the growth and production of siderophores were studied in the
      presence of different concentrations of free iron in vitro with M. smegmatis and
      virulent, avirulent and low virulent strains of M. tuberculosis. Increase in the
      concentrations of iron caused an appreciable increase in the growth (as assessed
      by cell dry-weight and log viable counts) of all 4 strains. This was, however
      accompanied by a significant decrease in the production of both exochelins and
      mycobactins, suggesting that these siderophores are necessary only under iron
      deficient conditions. The growth and production of siderophores were
      significantly higher with the virulent strain of M.tuberculosis than with the
      avirulent (or) the low virulent strains.

PMID- 8275023
TI  - Sub-retroviral particles as gene transfer vectors that by-pass retrovirus
      receptor interaction restrictions.
AB  - Retroviral infection initiates with the binding of the virus envelope protein to
      cell membrane receptors. However, it is unclear whether this interaction is
      necessary for subsequent events required to establish infection. To address this
      problem subretroviral particles containing a retroviral vector genome carrying a
      beta-galactosidase (beta-gal) gene have been microinjected into cells. Here we
      show that such cells become infected as judged by expression of beta-gal
      activity, suggesting that virus-receptor interaction is not required for
      infection. Such subretroviral particles lacking an envelope may be useful both
      for safer gene transfer procedures and gene transfer to cells that do not express
      the cognate virus receptor.

PMID- 8275024
TI  - Sequential deletion of DNA by use of remodeled pUC18 and pUC19 vectors.
AB  - pUC18 and pUC19 vectors were remodeled by replacement of their EcoO109I-NdeI
      portion with a "buffer sequence" of approximately 2.3 kilobase pairs derived from
      human genomic DNA. By use of the resulting plasmids, one can delete a target DNA
      that has been inserted into the polycloning site, deleting the buffer sequence at
      the same time, after linearization with an appropriate restriction enzyme that
      cleaves at the polycloning site. After the undeleted portion of the buffer
      sequence is cleaved off at the unique EcoRV site existing at its end, the plasmid
      can be recircularized for nucleotide sequencing from the deleted end of the
      target DNA. Thus the remodeled vectors enable deletion of DNAs by this simple
      method.

PMID- 8275025
TI  - In vitro protein synthesis in Hymenolepis diminuta, a rat intestinal cestode.
AB  - Helminth parasitic infestations are of great concern to the health of man and
      other animals. Limited studies have been carried out on the process of protein
      synthesis which, apart from having academic importance, could possibly provide a
      target for drug attack. In the present study distribution pattern of newly
      synthesized proteins in Hymenolepis diminuta, a rat intestinal cestode, has been
      worked out. The worms absorbed and incorporated about 21% and 3.8% of the amino
      acids added to the incubation medium, respectively. In other words, 18.3% of the
      absorbed amino acids was incorporated into proteins. Absorbed amino acids were
      distributed between washed cell debris (unbroken cells, nuclei, etc.) and crude
      extract in a ratio of 1:12. Cytosolic, microsomal and mitochondrial fractions
      received 72%, 3.2% and 6.6% amino acids, respectively. The mitochondrial
      membranes and the matrix shared equally the absorbed amino acids. The
      distribution pattern of amino acid incorporation was, however, different from
      that of absorption. The incorporation ratio between washed cell debris and crude
      extract was 1:3.7. The cytosolic, microsomal and mitochondrial fractions received
      32.8%, 8.6% and 18.4% of the incorporated amino acids, respectively. Within
      mitochondria incorporation was more in membranes than in the matrix. The ratios
      of incorporated versus free-pool amino acids in different fractions varied widely
      from 1:0.54 to 1:11.

PMID- 8275026
TI  - Effect of ADP-ribosylation reaction on bull testis chromatin.
AB  - Polynucleosomes prepared from bull testis nuclei were characterized: DNA length,
      by agarose gel electrophoresis, and distribution of poly(ADP-ribose)polymerase
      activity, by incubation with 0.64mM NAD were determined. Maximal activity was
      found in nucleosome fractions of 3-5 units. Chromatin fragments (5-2 kbp
      polynucleosomes) were analysed by circular dichroism in both native and ADP
      ribosylated forms. The spectrum of the endogenously ADP-ribosylated
      polynucleosomes, compared to the native fraction, exhibited a higher ellipticity
      value and a shift of the cross-over point towards the lowest wavelengths,
      behaving like an H1-depleted chromatin.

PMID- 8275027
TI  - Mapping of the region of the heavy chain of myosin subfragment 1 that can be
      crosslinked to the alkali light chains.
AB  - Earlier studies have shown that the presence of MgATP considerably diminishes the
      efficiency of crosslinking of the alkali light chains to the heavy chain of
      myosin subfragment 1 (S1) with dithiobis (succinimidylpropionate) (DSP). To
      localize the region of the nucleotide-induced change, a non-cleavable analog of
      DSP, disuccinimidyl suberate (DSS) was used. The products of crosslinking between
      the alkali light chains and the 27 kDa tryptic fragment of the heavy chain were
      isolated and further cleaved with N-chlorosuccinimide (NCS) or with formic acid.
      Mapping of the resulting peptides on SDS gels locates the crosslinking site(s) in
      the heavy chain region spanning residues 42-112.

PMID- 8275028
TI  - Simple purification and secondary structure evaluation of Sendai virus
      neuraminidase water soluble fragment.
AB  - We have developed a quick and simple method to purify the water soluble fragment
      of Sendai virus neuraminidase (cHN). We used the trifluoperazine (TFP) as
      detergent because of its ability to selectively solubilize the HN (Baiocchi et
      al., (1988) FEBS Lett. 238, 171-174). Here we describe conditions by which
      trypsin produces the cHN from the TFP treated virions. The cHN is further
      purified by size exclusion chromatography and it fully retains the neuraminidase
      activity and the allosteric inhibitory site as described in (Dallocchio et al.,
      (1991) Biochem. Int. 25, 663-668). Both circular dichroism (CD) spectra, analyzed
      by deconvolution methods and secondary structure prediction were used to assess
      the secondary structure of cHN.

PMID- 8275029
TI  - Promotion of fetal liver cell engraftment in irradiated mice by activated T
      lymphocytes.
AB  - The promoting effect of T lymphocytes on hematopoietic cell engraftment was
      studied in lethally irradiated CBA and Balb/c mice by transplantation of either
      liver cells from Balb/c fetuses (FLBalb) or FLBalb plus Balb/c T lymphocytes
      (TBalb). Additional groups of lethally irradiated CBA and Balb/c mice received T
      lymphocytes only, either from CBA (TCBA) or from Balb/c donors. Injection of
      TBalb lymphocytes had no effect on the splenic indices (SI) nor on the numbers of
      colony-forming units in the spleens (CFU-S) of FLBalb-transplanted Balb/c mice on
      day 7. In contrast, it increased these parameters in the CBA recipients of FLBalb
      in a T cell-dose dependent fashion and it stimulated their hematologic recovery
      on day 20 following irradiation. TCBA and TBalb lymphocytes transplanted alone
      did not induce CFU-S in syngeneic recipients but promoted the development of CFU
      S of endogenous origin in the histoincompatible mice. The development of CFU-S
      was enhanced in the FLBalb-transplanted Balb/c mice by injection of TBalb
      lymphocytes previously stimulated in vitro with irradiated CBA splenocytes,
      phorbol myristate acetate (PMA), phytohemagglutinin (PHA) or concanavalin A
      (conA). This effect was associated with an increased survival rate of the
      recipient mice. Daily injections for 6 days of a culture supernatant from a
      mixture of TBalb cells and irradiated CBA splenocytes, but not from irradiated
      CBA splenocytes alone, promoted the development of CFU-S in FLBalb-transplanted
      Balb/c recipients. However, the supernatant of stimulated TBalb cells was less
      efficient than the stimulated T cells themselves.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8275030
TI  - Autologous bone marrow transplantation for acute lymphoblastic leukemia.
AB  - Between December 1979 and February 1991, 89 patients with ALL received autologous
      BMT. Median patient age was 18.4 years. Ten patients were in first remission, 52
      were in second or greater remission and 27 were in relapse at the time of
      transplant. Conditioning regimens utilized chemotherapy alone (5 patients) or in
      combination with 10-15.75 Gy total body irradiation (84 patients). Disease-free
      survival at 1 year is 50% for patients transplanted in first remission, 27% for
      those in > or = second remission and 8% for patients in relapse. Pre- and post
      transplant variables were evaluated in univariate and multivariate analyses for
      their effect on survival and relapse. Factors significantly associated with
      improved survival were being transplanted in first remission and achieving a self
      sustained platelet count > or = 20 x 10(9)/l in a shorter period of time. A
      decreased relapse rate after transplant was associated with a lower white blood
      count at diagnosis, being transplanted in first remission and not being
      transplanted in relapse.

PMID- 8275031
TI  - Busulphan and melphalan prior to autologous bone marrow transplantation.
AB  - Twenty-four patients with a variety of malignant diseases (13 lymphoma, 4
      myeloma, 1 ALL, 6 solid tumours) were treated with the alkylating agents
      busulphan and melphalan as a preparative regimen for autologous BMT. Thirteen
      males and 11 females, aged 27-53 years (median 39.5 years) received oral
      busulphan 1 mg/kg q6 h on days -6 to -3, followed by i.v. melphalan 140 mg/m2 on
      day -2 and infusion of cryopreserved haemopoietic cells on day 0. The major
      toxicity seen was gastrointestinal with nausea, vomiting and diarrhoea in 17
      patients and severe mucositis in 22. There was no evidence of cardiotoxicity,
      nephrotoxicity, haemorrhagic cystitis or clinical signs of hepatic veno-occlusive
      disease. Twenty-three patients engrafted with the median duration of neutropenia
      (< 0.05 x 10(9)/l) 10 days (range 5-63 days) and thrombocytopenia (< 50 x
      10(9)/l) 43 days (range 5-350 days). Three patients died of transplant-related
      complications. Of 15 evaluable patients with active disease at BMT, 9 responded
      and 6 were refractory. Sixteen evaluable patients were in CR after BMT. Seven
      relapsed, 1 died in remission and 8 remain in CR 12-46 months (median 29 months)
      later. Of the group of 13 lymphomas, overall and relapse-free actuarial survival
      at 36 months was 64% and 58%, respectively, while for the entire group of 24
      patients these values were 39% and 34%. Busulphan and melphalan is a safe and
      inexpensive conditioning regimen for autologous BMT with acceptable toxicity and
      substantial antitumour activity particularly against lymphomas.

PMID- 8275032
TI  - Serum cytokine levels in patients undergoing bone marrow transplantation.
AB  - Daily serum samples collected during 6 autologous and 13 allogeneic BMT were
      assayed retrospectively for tumour necrosis factor-alpha (TNF), interleukin-6 (IL
      6) and C-reactive protein (CRP). In addition, for 6 allogeneic transplant
      patients soluble TNF receptor (sTNFR) levels were determined. IL-6 levels were
      regularly raised during febrile episodes and closely mirrored changes in serum
      CRP but were not predictive for non-infectious major transplant-related
      complications (TRC). Levels of TNF showed no such close association with
      infection and in contrast to previously reported data for allogeneic transplants
      having TRC, TNF levels were consistently detectable in only 3 of 9 patients. Pre
      transplant levels were not predictive for the development of TRC and no profile
      was recognized to be specific for a particular complication. In transplants with
      only minor complications TNF levels remained consistently undetectable. sTNFR
      levels increased in a more stable manner in association with TRC, suggesting that
      they may be a more suitable marker to monitor major TRC.

PMID- 8275033
TI  - Factors affecting hair regrowth after bone marrow transplantation.
AB  - Permanent alopecia after BMT has been reported as a side-effect associated with
      GVHD or after busulphan conditioning therapy, primarily in adults. We have
      reviewed children undergoing BMT to document the frequency of incomplete hair
      regrowth and to evaluate factors associated with this problem. Hair regrowth was
      studied in 74 children who survived > 6 months following BMT undertaken for
      malignant and non-malignant diseases. Alopecia was categorised as severe (< 50%
      of pre-transplant status), moderate (50-75%) or mild (> 75% but less than
      normal). Overall, 18 (24.3%) of 74 patients had mild (n = 5), moderate (n = 4) or
      severe (n = 9) alopecia. Risk factors for alopecia were presence of chronic GVHD
      (67%; p < 0.001), older age (p < 0.001) and prior cranial irradiation (42%; p =
      0.03). Alopecia occurred in children receiving either busulphan (31%) or total
      body irradiation (16%; p = 0.15) as conditioning therapy. The highest frequency
      was seen in patients conditioned with busulphan with or without melphalan and who
      received prior cranial irradiation and/or developed chronic GVHD (75%). These
      data indicate that alopecia after BMT in children is a significant problem and
      confirm, in children, the previously noted association between alopecia and
      chronic GVHD and busulphan. Further risk factors of older age and prior cranial
      irradiation are identified. Consideration needs to be given to the use of an
      alternative to busulphan in children who are of older age, have received prior
      cranial irradiation and/or are at increased risk of GVHD.

PMID- 8275034
TI  - The MHC influences acute graft versus host disease in MHC matched adults
      undergoing allogeneic bone marrow transplantation.
AB  - To determine whether the MHC plays an antigen non-specific role in the
      development of acute GVHD, the prevalence of acute GVHD in relation to MHC
      genotype was examined in 51 adult patients undergoing allogeneic BM grafting. The
      majority of patients received grafts from HLA-identical siblings. HLA-B7
      haplotypes were associated with a decreased risk of acute GVHD (2 of 15, p =
      0.005) whereas HLA-B44 haplotypes were associated with a higher risk of acute
      GVHD (11 of 14, p = 0.02). As these alleles have been reported previously as
      having opposite effects in relation to inflammatory mediators, these findings may
      have important implications with respect to donor selection and patient
      management.

PMID- 8275035
TI  - Intravenous pentoxifylline failed to prevent transplant-related toxicities in
      allogeneic bone marrow transplant recipients.
AB  - Based on encouraging results of a recently published study on the clinical
      usefulness of oral pentoxifylline (PTX) to reduce transplant-related toxicities,
      prophylactic pentoxifylline was administered to 31 consecutive allogeneic BMT
      recipients with hematological malignancies. Patients received PTX as a continuous
      infusion at increasing dose levels (0.50, 0.75, 1.00 and 1.25 mg/kg/h) starting 1
      day prior to the conditioning regimen. At all dose levels, PTX was well tolerated
      with no significant side-effects. When compared with a historical control group
      of 61 consecutively transplanted allogeneic BMT recipients, PTX patients did not
      appear to experience less gastrointestinal (moderate and severe mucositis: 100%
      vs 68%, p < 0.001), hepatic (hyperbilirubinemia > 1.5 mg/dl: 84% vs 30%, p <
      0.001) or renal (creatinine > 1.5 mg/dl: 16% vs 27%, NS) toxicity or to have a
      lower incidence of GVHD > or = grade III (21% vs 22%, NS). Using i.v. PTX, we
      were unable to reproduce the reduction in morbidity and mortality in patients
      undergoing BMT which has been described for prophylactic oral PTX.

PMID- 8275036
TI  - Constant intravenous pentoxifylline infusions in allogeneic marrow transplant
      recipients: results of a dose escalation study.
AB  - An uncontrolled open prospective dose escalation study of daily constant-rate 24
      h i.v. pentoxifylline (PTX) infusions was performed in 24 consecutive adult
      patients with hematologic malignancies undergoing allogeneic BMT. The objective
      of this study was to determine the maximum tolerable dose and to evaluate steady
      state plasma concentrations of PTX and its major active 5-hydroxylated metabolite
      (MI) with this application route. On each of three dose levels of PTX (10, 15 and
      20 mg/kg/day), eight patients were enrolled in this study. The prominent dose
      dependent and dose-limiting adverse effect attributable to PTX infusions was
      moderate to severe nausea and vomiting which occurred on the 15 mg/kg and 20
      mg/kg dose levels. In addition, one patient on each of the higher doses developed
      central nervous system toxicity which manifested as acute obtundation and
      myoclonias. Monitoring of steady-state plasma concentrations revealed that
      metabolite MI contributed 70-80% to both active compounds with a dose-dependent
      increase of parent drug and metabolite MI concentrations. In patients pretreated
      by high-dose busulfan and cyclophosphamide (CY), steady-state plasma
      concentrations of metabolite MI were significantly increased on all dose levels
      over those of patients who received total body irradiation and CY as a
      preparative regimen. Furthermore, impairment of excretory liver function led to
      significant accumulation of parent drug and metabolite MI. In conclusion,
      constant i.v. PTX infusions in allogeneic marrow transplant recipients are
      limited by dose-dependent nausea and vomiting with an estimated maximum tolerable
      dose in the range of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275037
TI  - Prospective evaluation of unrelated donor bone marrow transplantation. The
      International Marrow Unrelated Search and Transplant (IMUST) Study.
AB  - The International Marrow Unrelated Search and Transplant (IMUST) Study has
      prospectively assessed outcome of unrelated donor BMT (UD-BMT) in comparison with
      a matched cohort of patients treated by HLA-identical sibling BMT (ID-BMT). We
      report an interim analysis of the first 165 UD-BMT and 368 ID-BMT. Eighty-two
      percent of UD-BMT pairs were matched by serology for HLA-A, B and DR, 10% were
      less well matched and HLA matching data was incomplete in 8%. The Kaplan-Meier
      estimated probability of survival until day 400 was 0.42 (95% confidence limits
      0.33-0.51) after UD-BMT and 0.62 (0.56-0.68) after ID-BMT (p = < 0.001).
      Probability of engraftment by day 100 was 0.90 (0.85-0.95) and 0.95-0.99) after
      UD-BMT and ID-BMT, respectively (p = < 0.001). Cumulative probability of acute
      GVHD by day 100 was 0.52 (0.45-0.60) and 0.42 (0.37-0.47) after UD-BMT and ID
      BMT, respectively (p = 0.009). After UD-BMT, 52% of patients with early disease
      survived until day 400 (40-64%) and 27% (14-40%) with advanced disease (p = <
      0.001). Multifactorial analysis of survival showed success was related to the
      centre's experience of UD-BMT and this effect was modified by conditioning
      protocol. Increased probability of survival after UD-BMT in centres with most
      experience of the procedure is novel finding. We conclude UD-BMT is a more
      difficult procedure than ID-BMT but results are acceptable in patients with early
      disease and when UD-BMT is carried out in experienced centres.

PMID- 8275038
TI  - Growth hormone function and treatment following bone marrow transplant for
      neuroblastoma.
AB  - Previously, we reported that 26 children with stage III or IV neuroblastoma (NBL)
      treated with BMT grew poorly post-BMT and significantly worse than a comparison
      group of hematologic BMT patients. Furthermore, unlike the hematologic patients,
      there was no apparent catch-up growth. Six of these previously reported long-term
      (> 2 years) NBL patients surviving BMT were evaluated with growth hormone (GH)
      provocative testing, frequent (every 20 min) overnight GH sampling and IGF-1
      determinations. Three of 6 patients were GH deficient based on subnormal
      responses to provocative stimuli and subnormal pooled 12 h GH values. Only one
      child had completely normal GH testing and his growth was normal. Four patients
      were tested with recombinant GH for a period of 12-21 months. Three patients
      demonstrated an improvement in their growth velocity on therapy. However, the
      overall response to GH treatment was significantly less than the growth response
      in children who are GH-deficient due to causes other than BMT. In summary, GH
      deficiency may be a frequent complication of BMT treatment of NBL. It also
      appears that the BMT treatment protocol employing total body irradiation and high
      dose melphalan may induce GH resistance.

PMID- 8275039
TI  - B cell reconstitution after human bone marrow transplantation: recapitulation of
      ontogeny?
AB  - Patients undergoing BMT have a long-lasting defect of B cell-mediated immunity,
      especially if chronic GVHD ensues. It has been postulated that the post
      transplant B cell abnormalities can be explained by the recapitulation of B cell
      ontogeny. To test this hypothesis, we studied the quantitative and phenotypic
      reconstitution of circulating B cells in 24 transplant recipients and compared it
      with normal ontogeny. The results confirm that a second round of ontogeny occurs
      in transplant recipients without chronic GVHD. This was evidenced by the pattern
      of quantitative B cell reconstitution (low-->high-->normal B cell counts), large
      B cell size and a high proportion of B cells overexpressing CD38, membrane IgM
      (mIgM) and membrane IgD (mIgD). The recapitulation of ontogeny was blunted in
      most patients with chronic GVHD, as evidenced by the absence of the overshoot of
      total B cells and by the relative lack of CD38high, mIgMhigh and mIgDhigh B
      cells. We conclude the post-transplant B cell development in patients without
      chronic GVHD parallels ontogeny. The limited ability of patients with chronic
      GVHD to re-enact B cell ontogeny may contribute to their longer-lasting and more
      severe humoral immunodeficiency.

PMID- 8275040
TI  - Practices for cytomegalovirus diagnosis, prophylaxis and treatment in allogeneic
      bone marrow transplant recipients: a report from the Working Party for Infectious
      Diseases of the EBMT.
AB  - During the past few years major progress has been made in the diagnosis and
      therapy of CMV infection after allogeneic BMT. The aim of this survey was to
      investigate the use of diagnostic techniques, use of prophylaxis and the
      therapeutic strategies among members of the EBMT. Seventy centers from 20
      countries responded to the survey. Sixty-seven centers (96%) routinely tried to
      diagnose CMV from the blood. Fifty-seven centers used standard or rapid isolation
      techniques. Thirty-seven centers used one of the newly developed techniques,
      antigenemia detection in leukocytes or PCR together with isolation, while 10
      centers used one of these two techniques without standard isolation. Fifty-five
      centers regularly performed bronchoscopy and bronchoalveolar lavage on the
      suspicion of CMV pneumonia but only 12 centers required detection of CMV in
      specimens from the lavage or lungs as the indication to start therapy; 31 centers
      started therapy on symptoms of pneumonia combined with CMV detection from any
      site. Prophylaxis was used in 54 centers (84%). The most commonly used regimen
      was high-dose acyclovir which was used by 42 centers, while seven centers used
      ganciclovir. The strategy of early therapy was used by 53 centers (76%) and was
      most frequently based on detection of viremia or CMV antigen in the blood. CMV
      pneumonia was treated by a combination of ganciclovir and i.v. immunoglobulin by
      64 centers, by foscarnet and immunoglobulin in 5 centers and by ganciclovir alone
      in 5 centers. CMV gastrointestinal disease was treated by antiviral therapy alone
      in 18 centers and by a combination of antiviral therapy and iv immunoglobulin in
      46 centers.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275041
TI  - Reinduction of remission of chronic myeloid leukemia by donor leukocyte
      transfusion following relapse after bone marrow transplantation: recovery
      complicated by initial pancytopenia and late dermatomyositis.
AB  - A significant proportion of patients relapse after allogeneic BMT for CML. These
      relapses have been treated by induction of a graft-versus-leukemia effect by
      transfusing donor leukocytes. We have treated a 27-year-old woman with interferon
      and donor leukocyte transfusion and a complete haematological and cytogenetic
      remission was obtained coincident with the onset of GVHD. Her course was
      complicated by prolonged and profound pancytopenia which was fully reversed by
      the administration of rGM-CSF. She remains in CR with mild dermatomyositis due to
      chronic GVHD 17 months after the procedure.

PMID- 8275042
TI  - Severe adenoviral nephritis following bone marrow transplantation: successful
      treatment with intravenous ribavirin.
AB  - Invasive adenovirus infection is recognized as an unusual cause of serious end
      organ sequelae following BMT. Because symptomatic therapy may be inadequate for
      more serious infections, the use of investigational agents is justified. We
      describe a case of severe, progressive nephritis secondary to adenovirus serotype
      11 following BMT. Treatment with i.v. ribavirin led to prompt clinical
      improvement and resolution of adenovirus excretion.

PMID- 8275043
TI  - Severe idiopathic congenital aplastic anemia: role of hematopoietic growth
      factors.
AB  - A baby boy with constitutional aplastic anemia refractory to treatment with
      hematopoietic growth factors underwent BMT from an unrelated HLA-compatible
      donor. The BM failed to engraft but the combination of a conditioning regimen,
      immunosuppression and hematopoietic growth factors resulted in a recovery of the
      patient's own BM and a good outcome.

PMID- 8275044
TI  - Successful allogeneic bone marrow transplantation in an adult with aplastic
      anemia following orthotopic liver transplantation for non-A, non-B, non-C
      hepatitis.
AB  - A 29-year-old male patient presented with acute liver failure from non-A, non-B
      and non-C hepatitis, necessitating orthotopic liver transplantation. After
      operation he developed progressive pancytopenia on the basis of aplastic anemia,
      which was probably hepatitis associated. After therapy with GM-CSF had failed, he
      underwent allogeneic BMT from his HLA genotypically identical brother following a
      conditioning regimen of CY 50 mg/kg x 4 and 500 cGy total lymphoid irradiation.
      He engrafted promptly but transfusion dependency did not resolve until CMV
      viremia was treated with ganciclovir. The patient is alive and well 2 years after
      BMT.

PMID- 8275045
TI  - Successful treatment of Mucor pneumonia in a patient with relapsed lymphoblastic
      leukemia after bone marrow transplantation.

PMID- 8275046
TI  - Recombinant human erythropoietin for long-term persistent anemia after major ABO
      incompatible bone marrow transplantation.

PMID- 8275047
TI  - Cytomegalovirus mortality after bone marrow transplantation for thalassaemia.

PMID- 8275048
TI  - Effects of ageing on the motor unit: a brief review.
AB  - This review briefly summarizes the current state of knowledge regarding age
      related changes in skeletal muscle, followed by a more in-depth review of ageing
      effects on animal and human motor units (MUs). Ageing in humans is generally
      associated with reductions in muscle mass (atrophy), leading to reduced voluntary
      and electrically evoked contractile strength by the 7th decade for most muscle
      groups studied. As well, contraction and one-half relaxation times are typically
      prolonged in muscles of the elderly. Evidence from animal and human studies
      points toward age associated MU loss as the primary mechanism for muscle atrophy,
      and such losses may be greatest among the largest and fastest MUs. However, based
      on studies in animals and humans, it appears that at least some of the surviving
      MUs are able to partially compensate for MU losses, as indicated by an increase
      in the average MU size with age. The fact that muscles in the elderly have fewer,
      but on average larger and slower, MUs has important implications for motor
      control and function in this population.

PMID- 8275049
TI  - Physiological responses to specific maximal exercise tests for cross-country
      skiing.
AB  - The present study attempted to quantify differences in peak physiological
      responses to pole-striding (PS), double poling on roller skis (DP), and diagonal
      striding on roller skis (DS) during maximal exercise. Six expert cross-country
      ski racers (3 M, 3 F) with a mean age of 20.2 +/- 1.3 yrs served as subjects.
      Testing was conducted on a motorized ski treadmill with a tracked belt surface.
      Expired air was analyzed continuously via an automated open-circuit system and
      averaged each 20 s. Heart rate was monitored via telemetry and arterialized blood
      was collected within 1 min of test termination and analyzed immediately for
      lactate. Peak values for heart rate and blood lactate did not differ among
      techniques. Peak oxygen uptake was higher for PS and DS versus DP whereas no
      difference was found between PS and DS. The VO2peak for DP was 77 and 81% of
      VO2peak for PS and DS, respectively. It was concluded that despite similar peak
      heart rate and blood lactate values, DP elicits a lower VO2peak than DS or PS and
      that PS responses appear to closely reflect those of DS.

PMID- 8275050
TI  - Metabolic adaptations to endurance training in older individuals.
AB  - The purpose of this study was to describe the effects of moderate intensity
      exercise training on the muscle energy utilization, blood flow, and exercise
      performance of four sedentary older individuals (58 +/- 4 yrs). Subjects trained
      the dominant forearm each day for 12 weeks. The nondominant arm was not trained
      and served as a within-subject control. 31P nuclear magnetic resonance
      spectroscopy (31P NMRS) was used to identify the power output in watts (W) at the
      onset, or threshold, of intracellular acidosis (IT) in the exercising muscle
      during progressive exercise tests to fatigue. After 6 weeks of training, power
      output at the IT increased by 14% (p < 0.05) in the dominant arm; however, an
      additional 6 weeks of the same exercise program failed to produce a further
      increase in IT power. IT power of the nondominant forearm was not changed. In the
      dominant forearm, endurance time for a submaximal wrist flexion test was
      increased 34% and 58% at 6 and 12 weeks, respectively. Maximal voluntary strength
      was not affected by training, nor was resting or exercising blood flow. The
      training program delayed the onset of intracellular acidosis during progressive
      exercise and increased the capacity for submaximal work. These effects did not
      appear to depend on an increase in muscle blood flow.

PMID- 8275051
TI  - Effect of cardiac-locomotor coupling on the metabolic efficiency of pedalling.
AB  - Coupling between cardiac and locomotor rhythms (CLC) has been reported while
      subjects exercise at cadences that are natural to them. The hypothesis that
      oxygen consumption (VO2) would be lower when subjects pedalled at the rate
      producing 1:1 coupling of heart and pedalling rates than when they pedalled at
      noncoupled rates was tested with 12 men on a cycle ergometer. At a moderate power
      output based on their VO2max, subjects pedalled at six different pedalling rates
      while VO2 and heart rate were measured. The pedalling rates were the preferred
      frequency, frequencies 15 and 30% above and below the preferred frequency, and
      the 1:1 coupled frequency. In 8 of the 12 subjects it was possible to fit their
      data with significant regression equations relating VO2 to pedalling rate, but in
      no subject was the 1:1 coupled state energetically beneficial, suggesting that
      any functional significance of CLC is unrelated to metabolic efficiency.

PMID- 8275052
TI  - Production and characterisation of monoclonal antibodies to the principle
      sonicate antigens of Porphyromonas gingivalis w50.
AB  - Protein antigens from whole cell sonicates of Porphyromonas gingivalis W50,
      previously shown to be discriminatory antigens for patients with adult
      periodontitis, were purified using SDS-PAGE. Electroeluted proteins were used to
      immunize mice for the production of monoclonal antibodies (mAbs). A combination
      of enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to
      screen hybridoma supernatants for mAbs. MAbs were successfully raised against
      M(r) 115,000, M(r) 55,000 and M(r) 47,000 antigens together with a second M(r)
      55,000 polypeptide which was a contaminant of the M(r) 55,000 antigen. No
      immunological cross-reactivity was found between these four proteins. The mAbs
      were used to examine the distribution of these antigens among fifteen P.
      gingivalis strains together with related oral bacteria using immunostaining of
      dot blots and Western blots. The antigens were confined to P. gingivalis with the
      M(r) 115,000 and M(r) 47,000 antigens being present in all strains tested. The
      distribution of the M(r) 55,000 antigens were slightly more restricted: one M(r)
      55,000 (outer membrane location) was present in nine of the fifteen P. gingivalis
      strains tested, while the other M(r) 55,000 (location unknown) was only absent
      from one strain. Whole cell ELISA demonstrated that the M(r) 115,000 and the
      outer membrane M(r) 55,000 antigen possess epitopes which are located on the
      surface of the bacterium.

PMID- 8275053
TI  - MDHM, a macrophage-activating product of Mycoplasma fermentans, stimulates murine
      macrophages to synthesize nitric oxide and become tumoricidal.
AB  - In continuation of previous work on macrophage activation by a Mycoplasma
      fermentans-derived product, originally named "mycoplasma-derived high mol. wt.
      material" (MDHM), we have investigated whether MDHM was capable of inducing
      synthesis of the reactive nitrogen intermediate nitric oxide (NO), thus rendering
      macrophages cytocidal. Mycoplasmas were first delipidated with acetone, and MDHM
      activity was then extracted with 50 mM 1-O-octyl-beta-D-glucopyranoside to yield
      a particularly active new preparation of MDHM which we have named MDHM-D (D for
      detergent). In combination with IFN-gamma, MDHM-D activated macrophages to
      produce reactive nitrogen intermediates and kill P815 mastocytoma cells in co
      culture. P815 target cells were chosen because they are TNF-resistant.
      Macrophages from the LPS-low responder strain C3H/HeJ were used to minimize
      interference from possible LPS contamination. MDHM-D activity in this system was
      strictly IFN-gamma-dependent. In the presence of 25 U/ml IFN-gamma MDHM-D gave a
      half maximal response at a dilution of 1/100,000, showing a parallel
      concentration dependency for nitrite production and cytocidal activity.

PMID- 8275055
TI  - Monitoring of early events of experimental woodchuck hepatitis infection: studies
      of peripheral blood mononuclear cells by cytofluorometry and PCR.
AB  - The peripheral blood mononuclear cells (PBMC) of woodchucks experimentally
      infected by woodchuck hepatitis virus (WHV) were examined simultaneously for the
      presence of membrane associated WHV antigens by cytofluorometry, and for WHV DNA
      and RNA sequences by the polymerase chain reaction (PCR). Four woodchucks were
      inoculated: two with a well-defined infectious inoculum and two with an inoculum
      obtained from an animal at the late incubation phase, which was positive for WHV
      DNA by PCR but still devoid of WHV markers. Infection was demonstrated in all
      four inoculated woodchucks by the appearance at different times of WHV DNA and
      WHV antigens in both leucocytes and serum. WHV DNA was first detected by PCR
      either in the serum (two cases) or in leucocytes (two cases). The mean percentage
      of cells positive for membrane associated WHsAg or WHcAg detected by
      cytofluorometry were 37% +/- 25 and 17% +/- 15 respectively. After 8 weeks, all
      inoculated animals were WHsAg positive in serum. These data suggest that PBMC are
      involved in the early events of hepadnavirus infection. They also show that sera
      which are positive by PCR for WHV DNA may transmit viral infection even while
      still seronegative for WHV markers and for WHV DNA by dot blot.

PMID- 8275054
TI  - Susceptibility of chicken embryos to group A streptococci: correlation with
      fibrinogen binding.
AB  - One problem in investigating group A streptococcal infections and virulence is
      the lack of appropriate in vivo models. In this study we introduce the chicken
      embryo model for determining virulence of Streptococcus pyogenes. We found that M
      protein positive strains, if administered intravenously, were highly virulent for
      12-day-old chicken embryos. The LD50 of the strains tested could be correlated
      directly with the amount of cell wall exposed M protein, which has been
      determined by the capacity of streptococci to bind fibrinogen and by the ability
      of streptococci to survive in fresh normal human blood. The number of colony
      forming units (cfu) of M+ strains necessary to kill 50% of embryonated eggs was
      significantly lower (< 10(2) cfu) than for M-variants (> 10(4) cfu). Albumin
      and/or IgG binding streptococcal cells, which can also take place in proteins of
      the M protein family which do not bind to fibrinogen, did not show that clear
      correlation to the virulence in chicken embryos that did fibrinogen binding.
      Application of anti-streptococcal M protein antisera from chicken and rabbit
      reduced the lethality of the chicken embryos. In contrast, no correlation was
      found between lethality of chicken embryos and the in vitro production of
      erythrogenic toxins by the administered strains. Thus the results indicate that
      the presence of M-protein with its fibrinogen binding activity on the
      streptococcal cell surface is necessary for virulence of group A streptococci in
      the chicken embryo model.

PMID- 8275056
TI  - The ability of peripheral blood mononuclear cells of rabbits infected with
      Treponema pallidum to produce IL-2.
AB  - It was previously found that the cell-mediated immune response involved in
      protection against Treponema pallidum is distinctly suppressed during some
      periods in the course of syphilis infection in rabbits. This may be a result of
      the weak ability of cells to produce Interleukin-2 (IL-2) as well as of IL-2
      absorption. The ability of peripheral blood mononuclear cells (PBMC) of
      syphilitic rabbits to produce IL-2 develops within the first two weeks after
      infection reaching a maximum in about the eleventh week. In infection of longer
      duration, this capability was distinctly lowered. This low level of activity (no
      higher than in PBMC of normal rabbits) was maintained for 31 weeks. The ability
      of PBMC to absorb IL-2, in parallel with its production, was found at the same
      time in the course of syphilis infection (7-11 weeks). In long-lasting syphilis
      (more than 12 weeks) both abilities seem to be inhibited. Sera of syphilitic
      rabbits were found to have a higher level of IL-2 inhibitor than those of normal
      rabbits. Only in syphilis lasting 9 to 11 weeks, when the production of IL-2 was
      the greatest, was the level of IL-2 inhibitor nearly the same as in normal rabbit
      sera. In syphilis lasting longer, the increased level of inhibitor was
      accompanied by a decreased ability of cells to produce IL-2. These findings
      suggest that IL-2 inhibitor may be bound to IL-2 or IL-2 receptor on T
      lymphocytes and in this way would lead to weakening of T cell function and
      resistance against Treponema pallidum infection.

PMID- 8275057
TI  - Specificity of rabbit antisera against the rough lipopolysaccharide of Salmonella
      minnesota strain R7 (chemotype Rd1P-).
AB  - Rabbit polyclonal antibodies against the lipopolysaccharide (LPS) of the Rd1P-
      mutant strain R7 of Salmonella minnesota were serologically characterized using
      R7 LPS, dephosphorylated LPS, deacylated LPS, deacylated, dephosphorylated and
      reduced LPS, and synthetic partial structures. The latter comprised partial
      structures of the core region of Rd1P- LPS bound to the beta 1-->6-linked
      glucosamine dissacharide with two amide-linked 3-hydroxytetradecanoic acid
      residues or artificial glycoconjugates comprised of the synthetic
      oligosaccharides coupled to bovine serum albumin. Using a passive hemolysis and
      an enzyme immunoassay, absorption and inhibition experiments, the antibody
      specificites present could be determined. One group of antibodies required
      components of the core region and the phosphorylated glucosamine disaccharide of
      the lipid A moiety for binding. The majority of phosphate-independent antibodies
      was directed against the trisaccharide L-glycero-alpha-D-manno-heptopyranose(1-
      >3)- L-glycero-alpha-D-manno-heptopyranose(1-->5)3-deoxy-D-manno-oct ulo sonic
      acid. Antibodies against the 1-->3- and 1-->7-linked heptose disaccharides and
      against a single heptose were also detected, however, with low titers. No
      antibodies were found which required the presence of fatty acids.

PMID- 8275058
TI  - The effect of cytokines on bactericidal activity of murine neutrophils.
AB  - A range of recombinant cytokines have now been shown to modify aspects of the
      phenotype and function of human and murine neutrophils. However, few reports
      describe modification of the bactericidal activity of neutrophils. We therefore
      examined the recombinant murine cytokines tumor necrosis factor-alpha (TNF-alpha,
      10-1000 ng ml-1) and granulocyte macrophage-colony stimulating factor (GM-CSF, 10
      1000 U ml-1) for their ability to increase the bacterial killing capacity of
      murine neutrophils. Neutrophils from either bone marrow (fresh or cultured), or
      peritoneal exudates, or abscesses, were pre-incubated with either cytokine for 30
      60 min and the killing of Proteus mirabilis, Escherichia coli, or Bacteroides
      fragilis was examined in the presence or absence of serum over a 90 min period.
      Only for one combination was a small but significantly enhanced level of
      bacterial killing observed, the phagocytic killing of P. mirabilis by peritoneal
      exudate neutrophils in the presence of GM-CSF and serum. With this exception
      there was no enhancement of bacterial killing for the range of combinations of
      neutrophils and bacterial species tested. In contrast, at the concentrations
      tested for effect on bactericidal activity, TNF-alpha and GM-CSF were able to
      significantly upregulate CR3 (but not Fc gamma RII) expression on mouse
      neutrophils. These results indicate that upregulation of CR3 as an index of
      neutrophil activation does not necessarily correlate with increased bactericidal
      activity.

PMID- 8275059
TI  - Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human
      monocytes to release tumour necrosis factor-alpha, interleukin-1 beta and
      interleukin-6.
AB  - Cytokines play a major role in the pathophysiology of septic shock. In this
      study, human peripheral blood monocytes were stimulated with peptidoglycan and
      teichoic acid, purified from a strain of Staphylococcus epidermidis. Polymyxin B
      (PM-B) was added to avoid the effects of possible contamination with endotoxin.
      Tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6
      (IL-6) in the supernates were measured by enzyme-linked immunosorbent assays.
      Peptidoglycan and teichoic acid induced TNF, IL-1, and IL-6 in a concentration
      dependent manner. Teichoic acid was a weaker inducer than peptidoglycan,
      especially for IL-1. Lipopolysaccharide from an E. coli strain was used as a
      control, being 100-1000 times more potent than peptidoglycan and teichoic acid.

PMID- 8275060
TI  - A review of the controlled trials of pharmacotherapy and psychotherapy in the
      treatment of bulimia nervosa.
AB  - The treatment literature on bulimia nervosa includes several double-blind placebo
      controlled studies, the majority of which examine the use of antidepressants in
      bulimia nervosa. The psychotherapy literature has focused heavily on the use of
      cognitive behavioral therapy (CBT) in the treatment of this eating disorder. Some
      studies have compared CBT to other types of therapy or waiting list controls. The
      following review will examine the methodology and outcome of the pharmacotherapy
      and psychotherapy treatment studies of bulimia nervosa. The authors conclude that
      while the studies indicate treatment is somewhat effective, there remains
      uncertainty regarding the long-term effectiveness of most of the reported
      treatments.

PMID- 8275061
TI  - Why and how do women recover from bulimia nervosa? The subjective appraisals of
      forty women recovered for a year or more.
AB  - As part of a larger study of recovery in bulimia nervosa, 40 women recruited by
      local advertisement and referral who were recovered from the disorder for a year
      or more (median recovery = 36 months) participated in semistructured interviews
      regarding factors they believed to be related to their recovery process. We asked
      how life experiences and important persons in their lives had helped or hindered
      their recovery, what aspects of bulimia nervosa they found hardest to change and
      what they would still like to change, what they felt they gave up by recovering,
      and their beliefs about the potential for full, lasting recovery. We further
      inquired about professional and nonprofessional treatments utilized, our
      subjects' satisfaction with care, and specific helpful and harmful elements in
      treatment. Spontaneous answers were coded from audiotaped interviews. The women
      reported diverse experiences, many of which were consistent with clinical and
      empirical accounts. Almost 90% had received some treatment by a mental health
      professional, and many also had utilized nonprofessional treatments, particularly
      Overeaters Anonymous; these treatments were described as helpful by the majority
      using them. Of note, although parents often provided some practical support for
      treatment, the majority of subjects reported that their mothers and fathers were
      more harmful than helpful in the recovery process.

PMID- 8275062
TI  - A follow-up study of 33 subdiagnostic eating disordered women.
AB  - Thirty-three female subjects with subdiagnostic DSM-III-R anorexia nervosa (SAN)
      and/or subdiagnostic bulimia nervosa (SBN) were reinterviewed 24 to 52 months
      (mean 41 months) after seeking treatment for an eating disorder. Subjects were
      administered a semistructured interview by telephone and assessed for level of
      functioning, eating disorder symptoms, course of illness, and treatment sought.
      During the course of the follow-up, 15 (46%) subjects went on to meet full DSM
      III-R criteria for AN and/or BN. At follow-up, 4 (12%) met full DSM-III-R
      criteria for AN and/or BN, 22 (67%) were subdiagnostic, and 6 (18%) had
      recovered. The high percentage of subdiagnostic women that eventually develop
      full DSM-III-R criteria for AN and/or BN and the low rates of recovery at 2 to 4
      years suggest that the current diagnostic criteria may be too restrictive.

PMID- 8275063
TI  - Prognostic value of pretreatment social adaptation in bulimia nervosa.
AB  - We evaluated several indices of pretreatment social adaptation (social and
      vocational adjustment, DSM-III-R Axis-V ratings, and "object-relations"
      capacities) as predictors of the response of 44 completers of a multimodal
      therapy for bulimia nervosa. Response was assessed using standard measures of
      eating and psychiatric symptoms. Hierarchical regressions revealed that
      pretreatment social adjustment explained substantial (and significant)
      proportions of variance in posttreatment binge/purge symptoms, after variance
      associated with (a) initial severity of eating symptoms and (b) concurrent
      psychiatric symptoms (at posttreatment) was accounted for. Hence, social
      adjustment emerged as a somewhat specific predictor of response of bulimic
      behaviors. Possible clinical implications of this apparent predictive effect are
      discussed.

PMID- 8275064
TI  - Cognitive-behavioral group psychotherapy of bulimia nervosa: importance of
      logistical variables.
AB  - Although much of the psychotherapy for psychiatric disorders is conducted on a
      weekly basis, several researchers in the field of bulimia nervosa have utilized a
      more intensive approach as a means to strengthen treatment effects. A second
      issue concerns the amount of emphasis that should be placed on encouraging the
      interruption of bulimic symptoms early in treatment. In the current study we
      systematically studied these two issues. Subjects were randomly assigned to one
      of four forms of cognitive-behavioral group psychotherapy, the four cells
      differing on the variables of intensity and emphasis on abstinence. The results
      indicate that a high intensity approach, an early abstinence approach, or a
      combination of these two approaches are all significantly more effective in
      inducing remission in patients with bulimia nervosa compared with a weekly
      psychotherapy that uses the same manual-based cognitive-behavioral therapy
      approach.

PMID- 8275065
TI  - Diagnosing binge eating disorder: level of agreement between self-report and
      expert-rating.
AB  - We assessed the correlation between a self-report questionnaire and an expert
      rating including an initial interview and a longitudinal evaluation on the
      diagnosis of binge eating disorder (BED) in a sample of 100 obese women
      participating in a treatment program for weight reduction. The level of
      diagnostic agreement between patient-rating and expert-rating with regard to the
      presence or absence of BED was modest, with a kappa value of .57. According to
      Shrout, Spitzer, and Fleiss (Archives of General Psychiatry, 44, 172-177, 1987)
      this represents fair to good agreement beyond chance. The self-report instrument
      did not produce higher estimates of the frequency of BED in this selected sample
      of treatment seekers than the expert-rating, as observed in studies on the
      epidemiology of bulimia nervosa in community samples. The questionnaire
      identified 40 cases of BED, the expert-rating 43 cases. The results indicate that
      the disagreement between self-report and interview was mainly due to discordances
      in three of the diagnostic criteria of BED--namely loss of control, marked
      distress regarding binge eating, and the frequency requirement of two binge
      eating episodes per week for a 6-month period. Inconsistencies between subjects
      and clinicians with regard to the definition of an overeating episode and with
      regard to the behavioral indicators of loss of control did not lead to
      differences between self-report and observer-rating in the final diagnosis of
      BED.

PMID- 8275066
TI  - Anorexia nervosa and total parenteral nutrition.
AB  - Anorexia nervosa can have a devastating outcome. There is a high rate of
      treatment failures and recidivism among anorectic patients. Further, it is
      generally accepted that unless one can effectuate a significant weight gain in
      these patients, treatment is even more likely to fail. Total parenteral nutrition
      (TPN) offers an alternative mode of treatment to be used in the armamentarium to
      successfully treat anorexia nervosa.

PMID- 8275067
TI  - Are the eating disorders related to obsessive compulsive disorder?
AB  - The evidence supporting the idea that the eating disorders of anorexia and
      bulimia nervosa may be related to obsessive compulsive disorder is reviewed with
      respect to studies in phenomenology, comorbidity, neurotransmitters, central
      nervous system functional metabolism, and treatment and outcome. Although no
      definitive conclusion can be drawn, research generated from the idea has refined
      our thinking on the eating disorders.

PMID- 8275068
TI  - Cognitive processes in dieting disorders.
AB  - This study is an empirical investigation of the prevailing notion that dieting
      disorder patients have more dysfunctional cognitions and cognitive styles than
      the nonclinical population. Groups of anorexics, bulimics, normal restrainers,
      and normal nonrestrainers completed three questionnaires and two repertory grids.
      Overall, the data supported a cognitive model of dieting disorders. Patients
      exhibited a lack of awareness of the role played by inner sensations in
      regulating weight and eating behavior, and emphasized black and white rules
      instead. Anorexic patients tended to evaluate self-worth almost entirely in terms
      of self-control. Both patient groups evidenced extreme negativity in their views
      of themselves, but anorexics showed a particularly severe sense of self
      isolation. Unlike bulimics, they extended a tendency to think in absolute terms
      from the area of eating to the rest of their lives. Thus, the psychopathology of
      the anorexic patient group appeared more severe than that of bulimics.

PMID- 8275069
TI  - Cephalic phase insulin release in bulimia.
AB  - Cephalic phase secretions are associated with the sight, smell, and taste of
      food, as opposed to its postingestional consequences. These secretions are
      thought to influence metabolism and eating behavior. Cephalic phase insulin
      release (CPIR), in particular, might be related to hunger and overeating. It was
      hypothesized that bulimics, who often show endocrine abnormalities, may have an
      altered CPIR that, in turn, might be related to the precipitation and maintenance
      of binges. This study investigated whether (1) the profile or magnitude of the
      CPIR in bulimics differs from that of non-eating disordered controls, (2) food
      ingestion alters subsequent CPIR, and (3) mood and desire to binge are related to
      CPIR. Findings indicated little abnormality in bulimics' profile of insulin
      secretion. Although biological variables were not related to hunger or desire to
      binge, for bulimics, dysphoric moods were. The results may suggest more complex
      determinants of binge eating than physiological state alone.

PMID- 8275070
TI  - Oral and dental complications in dieting disorders.
AB  - This study investigated the oral status and dental complications in patients with
      both anorexia and bulimia nervosa. Results revealed that prolonged periods of
      dietary restraint in anorexic patients did not result in changes to bacteria
      associated in dental caries. Furthermore, patients did not have lower decay rates
      or salivary flow but did have more acidic saliva. Moreover, both groups of
      patients revealed changes indicative of gingivitis and gingival recession but not
      necessarily of periodontitis when compared to control subjects.

PMID- 8275071
TI  - Feelings of Fatness Questionnaire: a measure of the cross-situational variability
      of body experience.
AB  - The Feelings of Fatness Questionnaire (FOFQ) was developed to assess the
      variability of bodily feelings of thinness-fatness across life situations. The
      FOFQ, three other conventional measures of perceptual and cognitive-affective
      body experience, the Beck Depression Inventory, and the Eating Attitudes Test
      were administered to 132 undergraduate women. The FOFQ demonstrated acceptable
      construct validity and revealed considerable variation in "felt" body experience
      across psychosocial contexts. Problems with summary measures of body experience
      and possible cognitive processes mediating the relationship between context and
      subjective body experience are discussed.

PMID- 8275072
TI  - Is the selective information processing of food and body words specific to
      patients with eating disorders?
AB  - The selective processing of food- and body size-related information was
      investigated using a modified version of the Stroop task. Anorexic and bulimic
      patients and matched female controls were compared on the basis of categorical
      (diagnosis), dimensional (restraint and drive for thinness) criteria, or both.
      The findings suggest that the phenomenon assessed by the Stroop paradigm is not
      exclusive to patients with a clinical eating disorder, but patients and those
      control subjects who are restrained eaters with a high drive for thinness share a
      selective processing of information related to shape and eating. The discussion
      focuses on the implications of these findings.

PMID- 8275073
TI  - Correspondence between the clinical assessment of eating-disordered patients and
      findings derived from questionnaires at follow-up.
AB  - Questionnaire scores were compared across three outcome groups in a follow-up of
      eating-disordered patients with onset of the disease during adolescence. Among a
      total of 40 patients, 7 continued to suffer from either anorexia or bulimia
      nervosa. Seven additional patients displayed partial syndromes and 26 had
      recovered. Both a semantic differential measuring body image and the Eating
      Attitudes Test (EAT) demonstrated limited evidence of clinical sensitivity by
      differentiating the three outcome groups. The Eating Disorders Inventory (EDI)
      did not discriminate the three outcome groups. Obviously, clinical interviews and
      self-report questionnaires tackle different facets of the eating disorders and,
      therefore, both should be used in outcome studies.

PMID- 8275074
TI  - Prevalence of self-induced vomiting and laxative/medication abuse among female
      adolescents: a longitudinal study.
AB  - In order to assess the prevalence and stability of weight reduction techniques
      utilized by adolescent females, three comprehensive samples of middle school and
      high school students (ages 12-18) were surveyed in the springs of 1984, 1989, and
      1992. All participants were enrolled in the same school district to ensure that
      the groups were demographically equivalent. The results demonstrated a
      significant decrease in the use of appetite suppressants among high school
      students. However, middle school females reported a significant increase in
      medication use and self-induced vomiting during the same 7-year period. Laxative
      abuse has persisted unchanged for a small segment of both populations.

PMID- 8275075
TI  - A case of Munchausen's syndrome in anorexia nervosa.
AB  - To the authors' knowledge this is the first report of a patient with Munchausen's
      syndrome occurring as comorbidity with anorexia nervosa. The Munchausen's
      symptoms, together with other self-damaging and addictive behaviors, were used
      interchangeably to avoid anorexic feelings. The Munchausen's syndrome and self
      damaging behavior in anorexia nervosa are discussed.

PMID- 8275076
TI  - Restricter anorexia nervosa in a thirteen-year-old sheltered Muslim girl raised
      in Lahore, Pakistan: developmental similarities to westernized patients.
AB  - An academically perfectionistic and interpersonally compliant 13-year-old girl
      raised in a traditional, sheltering Muslim home in Lahore, Pakistan developed
      restricter anorexia nervosa in the context of being teased about her weight by
      her closest friend and younger brother, and in a context of family weight
      preoccupation. Similarities to current pathogenetic hypotheses among Western
      adolescents are discussed.

PMID- 8275077
TI  - Human genetics at the Whitehead.

PMID- 8275078
TI  - Experimental models of human carcinogenesis.

PMID- 8275080
TI  - Is MHC matching as a primary criterion in kidney allocation justified?

PMID- 8275079
TI  - Flipping the tip of the X.

PMID- 8275081
TI  - The case for matching MHC genes in human organ transplantation.

PMID- 8275082
TI  - Site of (CCG) polymorphism in the HD gene.

PMID- 8275083
TI  - Mitotic errors in trisomy 21.

PMID- 8275084
TI  - Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver
      nuclear abnormalities and die before weaning.
AB  - Defects in nucleotide excision repair are associated with the human condition
      xeroderma pigmentosum which predisposes to skin cancer. Mice with defective DNA
      repair were generated by targeting the excision repair cross complementing gene
      (ERCC-1) in the embryonic stem cell line, HM-1. Homozygous ERCC-1 mutants were
      runted at birth and died before weaning with liver failure. Examination of organs
      revealed polyploidy in perinatal liver, progressing to severe aneuploidy by 3
      weeks of age. Elevated p53 levels were detected in liver, brain and kidney,
      supporting the hypothesised role for p53 as a monitor of DNA damage.

PMID- 8275085
TI  - Spontaneous and carcinogen-induced tumorigenesis in p53-deficient mice.
AB  - Using gene targeting techniques, mice that have been generated with two germ-line
      p53 null alleles (homozygotes) develop normally but are highly susceptible to
      early onset spontaneous tumours. Here, we show that mice with a single null p53
      allele (heterozygotes) produced in the same way are also susceptible to
      spontaneous tumours, but with a delayed onset compared to homozygotes. The most
      frequent tumour type in homozygotes was malignant lymphoma; in heterozygotes,
      osteosarcomas and soft tissue sarcomas predominated. Heterozygous mice treated
      with a liver carcinogen, dimethylnitrosamine, showed a decreased survival time in
      comparison to treated wild type mice, suggesting that the p53-deficient mice may
      be useful for some in vivo carcinogenesis assays.

PMID- 8275086
TI  - Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar
      rhabdomyosarcoma.
AB  - We have examined the structure and expression of the products associated with the
      t(2;13)(q35;q14) translocation associated with alveolar rhabdomyosarcoma. The
      chromosome 13 gene (FKHR) is identified as a member of the fork head domain
      family of transcription factors characterized by a conserved DNA binding motif.
      Polymerase chain reaction analysis demonstrates that a 5'PAX3-3' FKHR chimaeric
      transcript is expressed in all eight alveolar rhabdomyosarcomas investigated.
      Immunoprecipitation experiments detect the predicted fusion protein. These
      findings indicate that the t(2;13) generates a potentially tumorigenic fusion
      transcription factor consisting of intact PAX3 DNA binding domains, a truncated
      fork head DNA binding domain and C-terminal FKHR regions.

PMID- 8275087
TI  - Inversions disrupting the factor VIII gene are a common cause of severe
      haemophilia A.
AB  - Mutations in the factor VIII gene have been discovered for barely more than half
      of the examined cases of severe haemophilia A. To account for the unidentified
      mutations, we propose a model based on the possibility of recombination between
      homologous sequences located in intron 22 and upstream of the factor VIII gene.
      Such a recombination would lead to an inversion of all intervening DNA and a
      disruption of the gene. We present evidence to support this model and describe a
      Southern blot assay that detects the inversion. These findings should be valuable
      for genetic prediction of haemophilia A in approximately 45% of families with
      severe disease.

PMID- 8275088
TI  - Nonsense mutations in the C-terminal SH2 region of the GTPase activating protein
      (GAP) gene in human tumours.
AB  - GTPase Activating Protein (GAP) is involved in down-regulating normal ras
      proteins and in the signal transduction pathway of some growth factors. We have
      screened 188 human tumours for mutations in the catalytic domain and at the C
      terminal SH2 region GAP. Three nonsense mutations in basal cell carcinomas were
      detected in the SH2 region and no mutations could be demonstrated in the
      catalytic domain. We conclude that mutations in the SH2 region of GAP may play a
      role in tumorigenesis and that inactivating mutations of the GAP catalytic domain
      do not contribute to tumour development.

PMID- 8275089
TI  - A complex mutable polymorphism located within the fragile X gene.
AB  - While studying founder chromosomes in the fragile X syndrome, we have
      unexpectedly found linkage equilibrium to FRAXAC2, an Alu-associated
      microsatellite within the defective gene, FMR-1. DNA sequencing of 265
      chromosomes revealed 39 alleles and a complex microsatellite of form (GT)x-C
      (TA)y-(T)z. A mutation rate of 3.3% was observed but only among fragile X
      maternally derived meioses. Finding a second mutable locus within FMR-1 suggests
      that the target for tandem repeat instability may not be confined to the (CGG)n
      repeat alone and raises the possibility of an FMR-1 mutation mechanism involving
      microsatellites.

PMID- 8275090
TI  - Evidence for a mechanism predisposing to intergenerational CAG repeat instability
      in spinocerebellar ataxia type I.
AB  - Spinocerebellar ataxia type I (SCAI) is an autosomal dominant neurodegenerative
      disease caused by the expansion of a CAG trinucleotide repeat on chromosome 6p.
      Normal alleles range from 19-36 repeats while SCA1 alleles contain 43-81 repeats.
      We now show that in 63% of paternal transmissions, an increase in repeat number
      is observed, whereas 69% of maternal transmissions showed no change or a decrease
      in repeat number. Sequence analysis of the repeat from 126 chromosomes reveals an
      interrupted repeat configuration in 98% of the unexpanded alleles but a
      contiguous repeat (CAG)n configuration in 30 expanded alleles from seven SCA1
      families. This indicates that the repeat instability in SCA1 is more complex than
      a simple variation in repeat number and that the loss of an interruption
      predisposes the SCA1 (CAG)n to expansion.

PMID- 8275091
TI  - Widespread expression of the human and rat Huntington's disease gene in brain and
      nonneural tissues.
AB  - We have used RNA in situ hybridization to study the regional expression of the
      Huntington's disease gene (HD) and its rat homologue in brain and selected
      nonneural tissues. The HD transcript was expressed throughout the brain in both
      rat and human, especially in the neurons of the dentate gyrus and pyramidal
      neurons of the hippocampal formation, cerebellar granule cell layer, cerebellar
      Purkinje cells and pontine nuclei. Other brain areas expressed lower levels of
      the HD transcript without pronounced regional differences. Neuronal expression
      predominated over glial expression in all regions. HD mRNA was also expressed in
      colon, liver, pancreas and testes. The regional specificity of neuropathology in
      HD, which is most prominent in the basal ganglia, thus cannot be accounted for by
      the pattern of expression of HD.

PMID- 8275092
TI  - Dejerine-Sottas syndrome associated with point mutation in the peripheral myelin
      protein 22 (PMP22) gene.
AB  - Dejerine-Sottas syndrome is a hypertrophic, demyelinating neuropathy which
      appears to demonstrate autosomal recessive inheritance in most pedigrees.
      Clinical symptoms are similar but more severe than Charcot-Marie-Tooth disease
      type 1 (CMT1), of which the major subtype, CMT1A, results either from duplication
      of a 1.5-megabase DNA region in chromosome 17p11.2-p12 containing the myelin gene
      PMP22, or from PMP22 point mutation. Mutational analysis of the PMP22 coding
      region in two unrelated Dejerine-Sottas patients identified individual missense
      point mutations present in the heterozygous state. These findings suggest that
      Dejerine-Sottas syndrome can result from dominant point mutation alleles of
      PMP22.

PMID- 8275093
TI  - Localization of a gene for Fukuyama type congenital muscular dystrophy to
      chromosome 9q31-33.
AB  - Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive
      severe muscular dystrophy associated with an anomaly of the brain. Twenty-one
      FCMD families, 13 of them with consanguineous marriages, were analysed by genetic
      linkage analyses with polymorphic microsatellite markers to map the FCMD gene.
      Significant lod scores were obtained with the markers D9S58 (Zmax = 5.81 at theta
      = 0.06), D9S59 (Zmax = 4.33 at theta = 0.02), and HXB (Zmax = 3.28 at theta =
      0.09) on chromosome 9q31-33. Multipoint analysis placed FCMD between D9S58 and
      D9S59, with a maximum lod score of 16.93. These markers will be useful for
      presymptomatic, prenatal and carrier diagnosis of family members carrying FCMD,
      and they represent important resources for the identification of a gene
      responsible for FCMD.

PMID- 8275094
TI  - A homozygous insertion-deletion in the type VII collagen gene (COL7A1) in
      Hallopeau-Siemens dystrophic epidermolysis bullosa.
AB  - The Hallopeau-Siemens type of recessive dystrophic epidermolysis bullosa (HS
      RDEB) is a life-threatening autosomal disease characterized by loss of dermal
      epidermal adherence with abnormal anchoring fibrils (AF). We recently linked HS
      RDEB to the type VII collagen gene (COL7A1) which encodes the major component of
      AF. We describe a patient who is homozygous for an insertion-deletion in the FN
      4A domain of the COL7A1 gene. This defect causes a frameshift mutation which
      leads to a premature stop codon in the FN-5A domain, resulting in a marked
      diminution in mutated mRNA levels, with no detectable type VII collagen
      polypeptide in the patient. Our data suggest strongly that this null allele
      prevents normal anchoring fibril formation in homozygotes and is the underlying
      cause of HS-RDEB in this patient.

PMID- 8275095
TI  - Deletion of Y chromosome sequences located outside the testis determining region
      can cause XY female sex reversal.
AB  - An approach designed to map and generate mutations in the region of the short arm
      of the mouse Y chromosome, known to be involved in sex determination and
      spermatogenesis, is described. This relies on homologous Yp-Sxra pairing and
      asymmetrical exchange which can occur at meiosis in XY males carrying Sxra on
      their X chromosome. Such exchange potentially generates deficiencies and
      duplications of Yp or Sxra. Three fertile XY females were found out of about 450
      XY offspring from XSxra/Y x XX crosses. In all three, despite evidence for
      deletion of Y chromosomal material, the Sry locus was intact. Each deletion
      involved a repeat sequence, Sx1, located at a distance from Sry. Since expression
      of Sry was affected these results suggest that long range position effects have
      disrupted Sry action.

PMID- 8275096
TI  - A gene for Stargardt's disease (fundus flavimaculatus) maps to the short arm of
      chromosome 1.
AB  - Stargardt's disease (fundus flavimaculatus) is one of the most frequent causes of
      macular degeneration in childhood and accounts for 7% of all retinal dystrophies.
      It is an autosomal recessive condition characterized by a bilateral loss of
      central vision occurring at age 7-12 years. Genetic linkage analysis of eight
      families has assigned the disease locus to chromosome 1p21-p13. Multipoint
      linkage analysis and haplotype analysis has allowed us to establish the best
      estimate for location of the gene over the locus D1S435 (maximum lod score of
      12.66). Our results are consistent with the genetic homogeneity of this
      condition.

PMID- 8275097
TI  - Tobacco plants transformed with the O-acetylserine (thiol) lyase gene of wheat
      are resistant to toxic levels of hydrogen sulphide gas.
AB  - O-acetylserine (thiol) lyase (EC4.2.99.8) is the key enzyme in the cysteine
      biosynthetic pathway of plants and prokaryotes. The gene, cys1, encoding this
      enzyme was isolated from a wheat (Triticum aestivum L.) cDNA library, and its
      deduced amino acid sequence found to show 53% sequence identity with the O-acetyl
      serine (thiol) lyase of Escherichia coli and Salmonella typhimurium. The deduced
      peptide consists of 325 amino acids (34.1 kDa), contains a conserved motif for
      the binding of pyridoxal phosphate, a co-factor required for enzymatic activity,
      and an N-terminal region of 37 amino acid residues resembling chloroplast transit
      peptides. The identity of cys1 was further demonstrated through complementation
      of an E. coli cysteine auxotroph, which lacks O-acetylserine (thiol) lyase, by
      expression of the wheat gene. Northern blot analysis showed that cys1 is highly
      expressed in green vegetative and reproductive tissues and in the roots of wheat,
      as well as in the leaves of several plant species. Southern blot analysis
      demonstrated that the gene exists as a single copy in the wheat genome. Tobacco
      plants transformed with cys1 in the sense orientation (sense plants) or antisense
      orientation (antisense plants), under the control of the CaMV 35S promoter,
      showed high levels of transcripts. The O-acetylserine (thiol) lyase activity in
      transgenic plants was determined, and found to be three- to fivefold higher in
      sense plants than in control plants, but unaffected in antisense transformants.
      Fumigation experiments with toxic levels of hydrogen sulphide (H2S) gas showed
      that while sense transformants were highly resistant, control and antisense
      plants were severely damaged by the treatment.

PMID- 8275098
TI  - The ubiquitous presence of exopolygalacturonase in maize suggests a fundamental
      cellular function for this enzyme.
AB  - Exopolygalacturonase (exoPG) is a pectin-degrading enzyme abundant in maize
      pollen. Using immunochemistry and in situ hybridization it is shown that in
      addition to its presence in pollen, exoPG is also present in sporophytic tissues,
      such as the tapetum and mesophyll cells. The enzyme is located in the cytoplasm
      of pollen and of some mesophyll cells. In other mesophyll cells, the tapetum and
      the pollen tube, exoPG is located in the cell wall. The measurement of enzyme
      activity shows that exoPG is ubiquitous in the vegetative organs. These results
      suggest a general function for exoPG in cell wall edification or degradation.
      ExoPG is encoded by a closely related multigene family. The regulation of the
      expression of one of the exoPG genes was analyzed in transgenic tobacco. Reporter
      GUS activity was detected in anthers, seeds and stems but not in leaves or roots
      of transgenic plants. This strongly suggests that the ubiquitous presence of
      exoPG in maize is the result of the expression of different exoPG genes.

PMID- 8275099
TI  - Vesicle transport and processing of the precursor to 2S albumin in pumpkin.
AB  - Cell fractionation of pulse-chase-labeled developing pumpkin cotyledons
      demonstrated that proprotein precursor to 2S albumin is transported from the
      endoplasmic reticulum to dense vesicles and then to the vacuoles, in which pro2S
      albumin is processed to the mature 2S albumin. Immunocytochemical analysis showed
      that dense vesicles of about 300 nm in diameter mediate the transport of pro2S
      albumin to the vacuoles. The primary structure of the precursor (16,578 Da) to
      pumpkin 2S albumin has been deduced from the nucleotide sequence of an isolated
      cDNA insert. The presence of a hydrophobic signal peptide at the N-terminus
      indicates that the precursor is a pre-proprotein that is converted into pro2S
      albumin after cleavage of the signal peptide. N-terminal sequencing of the pro2S
      albumin in the isolated vesicles revealed that the signal peptide is cleaved off
      cotranslationally on the C-terminal side of alanine residue 22 of prepro2S
      albumin. By contrast, posttranslational cleavages occur on the C-terminal sides
      of asparagine residues 35 and 74, which are conserved among precursors to 2S
      albumin from different plants. Hydropathy analysis revealed that the two
      asparagine residues are located in the hydrophilic regions of pro2S albumin.
      These findings suggest that a vacuolar processing enzyme can recognize exposed
      asparagine residues on the molecular surface of pro2S albumin and cleave the
      peptide bond on the C-terminal side of each asparagine residue to produce mature
      2S albumin in the vacuoles.

PMID- 8275100
TI  - Identification of a disease resistance locus in Arabidopsis that is functionally
      homologous to the RPG1 locus of soybean.
AB  - A new disease resistance locus in Arabidopsis, RPS3, was identified using a
      previously cloned avirulence gene from a non-Arabidopsis pathogen. The avrB
      avirulence gene from the soybean pathogen Pseudomonas syringae pv. glycinea was
      transferred into a P. syringae pv. tomato strain that is virulent on Arabidopsis,
      and conversion to avirulence was assayed on Arabidopsis plants. The avrB gene had
      avirulence activity on most, but not all, Arabidopsis ecotypes. Of 53 ecotypes
      examined, 45 were resistant to a P. syringae pv. tomato strain carrying avrB, and
      eight were susceptible. The inheritance of this resistance was examined using
      crosses between the resistant ecotype Col-0 and the susceptible ecotype Bla-2. In
      F2 plants from this cross, the ratio of resistant:susceptible plants was
      approximately 3:1, indicating that resistance to P. syringae expressing avrB is
      determined by a single dominant locus in ecotype Col-0, which we have designated
      RPS3. Using RFLP analysis, RPS3 was mapped to chromosome 3, adjacent to markers
      M583 and G4523, and < or = 1 cM from another disease resistance locus, RPM1. In
      soybean, resistance to P. syringae strains that carry avrB is controlled by the
      locus RPG1. Thus, RPG1 and RPS3 both confer avrB-specific disease resistance,
      suggesting that these genes may be homologs.

PMID- 8275101
TI  - Functional expression of the Erwinia uredovora carotenoid biosynthesis gene crtl
      in transgenic plants showing an increase of beta-carotene biosynthesis activity
      and resistance to the bleaching herbicide norflurazon.
AB  - Among the enzymes involved in carotenoid biosynthesis, phytoene desaturase is
      considered to be a rate-limiting enzyme in this pathway and is also the target of
      many bleaching herbicides. This enzyme shows diversity concerning its function
      and amino acid homology among various organisms. The phytoene desaturase gene
      crtl of Erwinia uredovora was expressed, the 5'-region of which was fused to the
      sequence for the transit peptide of a pea Rubisco small subunit, in tobacco
      plants under the control of the CaMV 35S promoter. This chimeric gene product was
      targeted into chloroplasts and processed in the transgenic plants. The production
      and processing of the corresponding protein could be demonstrated by Western
      blotting. Immunogold localization showed that the location of the gene product
      Crtl was preferentially in the thylakoids. A radioactive labeling study using the
      leaves demonstrated enhanced activity for the synthesis of beta-carotene. In
      addition, the transgenic tobacco acquired elevated resistance to the bleaching
      herbicide norflurazon.

PMID- 8275102
TI  - The carrot secreted glycoprotein gene EP1 is expressed in the epidermis and has
      sequence homology to Brassica S-locus glycoproteins.
AB  - Non-embryogenic carrot suspension cells secrete the EP1 glycoprotein. A cDNA
      clone encoding EP1 was isolated and sequenced. The EP1 sequence revealed a region
      of homology with Brassica S-locus glycoprotein genes, an Arabidopsis S-like gene
      and putative S-like receptor protein kinases from maize and Arabidopsis. EP1 gene
      expression, analysed by in situ mRNA localization, was detected in cells located
      at the surface of the seedling: in the epidermis of the root, the hypocotyl and
      the cotyledons, in the root cap, and in a crescent of cells in the apical dome of
      the shoot. In developing seeds, expression was most pronounced in both the inner
      and outer integument epidermis.

PMID- 8275103
TI  - Differential gene expression in nematode-induced feeding structures of transgenic
      plants harbouring promoter-gusA fusion constructs.
AB  - Sedentary plant-parasitic nematodes are able to induce specialized feeding
      structures in the root system of their host plants by triggering a series of
      dramatic cellular responses. These changes presumably are accompanied by a
      reprogramming of gene expression. To monitor such changes, a variety of promoter
      gusA fusion constructs were introduced into Arabidopsis and tobacco. Transgenic
      plants were analysed histochemically for GUS activity in the nematode feeding
      structures after infection with either Heterodera schachtii or Meloidogyne
      incognita. Promoters of the Cauliflower Mosaic Virus 35S gene, the bacterial
      nopaline synthase, rooting loci (rol) and T-cyt genes and the plant-derived
      phenylalanine ammonia-lyase I gene, which are highly active in non-infected
      roots, were all downregulated in the feeding structures as indicated by the
      strong decrease of GUS activity inside these structures. Less stringent
      downregulation was observed with chimeric gusA fusion constructs harbouring
      truncated rolB and rolC promoter sequences. Similar observations were made with
      transgenic Arabidopsis lines that carried randomly integrated promoterless gusA
      constructs to identify regulatory sequences in the plant genome. Most of the
      lines that were selected for expression in the root vascular cylinder
      demonstrated local downregulation in feeding structures after infection with H.
      schachtii. The reverse pattern of GUS activity, a blue feeding structure amidst
      unstained root cells, was also found in several lines. However, GUS activity that
      was entirely specific for the feeding structures was not observed. Our data show
      that the expression of a large number of genes is influenced during the
      development of the nematode feeding structures.

PMID- 8275104
TI  - Four members of the maize beta-tubulin gene family are expressed in the male
      gametophyte.
AB  - Four different beta-tubulin cDNA clones have been identified in maize pollen cDNA
      libraries. Three of the four cDNA clones represent new maize beta-tubulin genes
      that have been designated tub3, tub4 and tub5. It is shown that the beta-tubulin
      gene family in maize is more complex than originally anticipated and more complex
      than those in vertebrates. In the maize beta-tubulin gene family the tub3, tub4
      and tub5 genes are shown to represent small beta-tubulin gene subfamilies.
      Differences in the abundance of the tub3, tub4 and tub5 transcripts are seen
      among vegetative and reproductive tissues. The tub3 and tub4 transcripts are most
      abundant in pollen. In spikelet development, abundance of the tub3 transcript
      increases markedly from the 0.7 cm to the 1.0 cm spikelets whilst the levels of
      tub4 transcript closely resemble those of total beta-tubulin transcript in the
      organs examined. The tub3 and tub4 genes appear to have diverged recently in the
      evolution of the maize beta-tubulin gene family. The tub5 gene is expressed in
      pollen but its transcript is most abundant in maize vegetative tissues.

PMID- 8275105
TI  - Detection of antisense transcripts in transgenic plants by RT-PCR.
AB  - A reverse transcriptase-polymerase chain reaction (RT-PCR) where one
      oligonucleotide primer is end-labelled has been used to analyse expression in
      transgenic plants carrying antisense gene constructs. Specific detection of both
      sense and antisense RNA transcripts of the spliceosomal protein gene, U2B'', was
      achieved using the same pair of oligonucleotide primers. To maintain specificity,
      a reaction step in which reverse transcriptase was inactivated and RNA digested
      was found to be essential.

PMID- 8275106
TI  - An improved method of plant megabase DNA isolation in agarose microbeads suitable
      for physical mapping and YAC cloning.
AB  - The isolation of high quality megabase DNA from plant cells that is susceptible
      to a variety of molecular reagents is a critical first step in the physical
      analysis of complex genomes. A method for the isolation of such DNA by
      encapsulating plant protoplasts in agarose microbeads is presented. In comparison
      with the conventional agarose plug method, microbeads provide a dramatic increase
      in the surface area yielding megabase DNA that can be treated essentially as an
      aqueous DNA solution. Examples of the utility of DNA prepared by this technique
      for physical mapping, partial restriction enzyme digestion and cloning of large
      inserts as YACs are presented.

PMID- 8275107
TI  - PCR amplification of microdissected wheat chromosome arms in a simple 'single
      tube' reaction.
AB  - A novel method for the adaptor-mediated PCR amplification of microdissected
      chromosome arms is described. This simple and versatile protocol eliminates the
      need for enzymatic micromanipulation in nanoliter volumes and permits the
      efficient amplification of as little as two wheat chromosome arms in a 'single
      tube' reaction.

PMID- 8275108
TI  - [Diffuse suffering. Rehabilitation of patients with fibromyalgia].

PMID- 8275109
TI  - [Diffuse suffering. Fibromyalgia--just hysterical women?].

PMID- 8275110
TI  - [Diffuse suffering. Research as participation].

PMID- 8275111
TI  - [Diffuse suffering. Various professional groups' viewpoint on fibromyalgia--a
      cross-professional Scandinavian pilot study].

PMID- 8275112
TI  - [Quality assurance: toward total quality in health services].

PMID- 8275113
TI  - [Diffuse suffering. Suspect behavior of patients with illness without objective
      medical findings].

PMID- 8275114
TI  - [Nursing research: focus on quality of life in nursing--something new?].

PMID- 8275115
TI  - [Professional development through guidance].

PMID- 8275116
TI  - [Psychiatric nursing homes in Rogaland--before, now and in the future].

PMID- 8275117
TI  - [Who is the patient?].

PMID- 8275118
TI  - [Pilot project in Ulleval--early rehabilitation of elderly patients with femoral
      neck fractures].

PMID- 8275119
TI  - [Screening of child development--a possible aid in Norwegian health centers?].

PMID- 8275121
TI  - [Nursing education and clinical studies].

PMID- 8275120
TI  - [Care of the aged. Elderly immigrants--what happens to them?].

PMID- 8275122
TI  - [Diffuse suffering. The new "war sailors"? Results of 2 studies].

PMID- 8275124
TI  - Where are the primary care physicians?

PMID- 8275123
TI  - From hospital to system. How Sister Ellen Lawlor made the leap. Interview by Jill
      E. Sherer.

PMID- 8275125
TI  - The voices of reform. The final stretch. Interview by Renee Blankenau.
AB  - Following a complex research and development process last year that led to the
      drafting of a comprehensive health care reform proposal, President Bill Clinton
      presented the U.S. Congress and the nation with an outline for reform in
      September, and followed up with a detailed plan and with a reform bill in
      October. Now it's Congress' turn to respond. Hospitals & Health Networks' senior
      editor Renee Blankenau interviewed 11 members of Congress whose views represent a
      broad spectrum of congressional opinion. What version of federal reform will
      emerge this year? These legislators have the inside track.

PMID- 8275126
TI  - Voices of reform. The AHA: policy, advocacy and the tools for reform.
AB  - In three thoughtful essays, with an introduction by president Dick Davidson,
      executives at the AHA discuss the policy and political aspects of the reform
      process, and the organization's reform vision, including the development of tools
      for its membership.

PMID- 8275127
TI  - Voices of reform. The stakeholders. Leaders of special-interest groups outline
      their ideas on reform.

PMID- 8275128
TI  - The AHA's NOVA awards. Making collaboration work.
AB  - What do communities as diverse as Akron, OH, Colville, WA, Laconia, NH, Denver
      and Philadelphia have in common? They all have health care organizations involved
      in collaborative activities among providers and between providers and community
      groups. And for their achievements, those organizations are recipients of the
      AHA's NOVA Award.

PMID- 8275129
TI  - Physicians. Profiling in practice.

PMID- 8275130
TI  - Fighting AIDS at home. Hospitals, physicians seek community AIDS strategies.
AB  - Experts say collaboration and coordination of AIDS services among providers and
      agencies can improve and streamline the delivery of care, as well as reduce
      unnecessary costs. Meanwhile, White House AIDS policy coordinator Kristine Gebbie
      has definite ideas about the next steps in handling the AIDS crisis.

PMID- 8275131
TI  - Seattle. Reform law motivates providers and payers to form networks.

PMID- 8275132
TI  - Data watch. Outcomes on the upswing.

PMID- 8275133
TI  - Medical center gets facility face-lift, attitude adjustment.

PMID- 8275134
TI  - Proposed CDC rule on TB masks leaves hospitals gasping.

PMID- 8275135
TI  - Laws sought to guard health data from falling into the wrong hands.

PMID- 8275136
TI  - Could federal regs changes spell trouble for foreign therapists?

PMID- 8275137
TI  - Managing costs means managing resource utilization.

PMID- 8275138
TI  - Preventing stagnation of a CE department.

PMID- 8275139
TI  - On acknowledging prior publication.

PMID- 8275140
TI  - User facility reporting requirement update. Interview by Mary Beth Hatem.

PMID- 8275141
TI  - Using laptop computers as a BMET field service tool.
AB  - This system has been in operation for approximately two years at the time of this
      writing, and involves more than a dozen laptop computers. The true test of
      whether something is successful is the degree of acceptance that is generated by
      the people who must use it. Approximately two months after beginning this
      process, our biomedical equipment technicians (BMETs) asked us to expand
      utilization of this system to a greater segment of our client base because it was
      so much simpler than our prior paper method. Our ability to track events that
      occur in the field is much improved with any problems identified in procedures
      being communicated through the private comments. Not only are the printed PM
      forms far more legible than the prior hand-entered results, but the concept of
      test-to-standards now is far more practical because the testing protocols are a
      keypress away, and the question of whether the technician would take the time to
      look up in the cumbersome procedure manuals those things that he or she was only
      slightly unsure of is addressed. Additionally, we have seen more than a 25%
      reduction in data-handling associated with the processing of the PM inspections
      in this fashion. Even with the time necessary to create the data disks, upload
      them, and process them through the filter, we are still saving substantial time
      over the manual handling of paper.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275142
TI  - Case study: patient-coupled device interaction produces arrhythmia-like artifact
      on electrocardiographs.

PMID- 8275143
TI  - Application of polytetrafluoroethylene (PTFE) membranes to control interference
      effects in a glucose biosensor.
AB  - The implantable feedback-controlled insulin delivery system provides the greatest
      potential for the control of certain types of diabetes mellitus. The development
      of an implantable glucose sensor is thus a prerequisite. A glucose biosensor
      using the enzyme glucose oxidase immobilized on fine carbon powder has been
      developed. Its in-vitro behavior is investigated in the presence of interfering
      substances commonly encountered in human blood and other body fluids. Here, in
      vitro interference tests carried out on this sensor with polytetrafluoroethylene
      (PTFE) membranes are described. The authors used PTFE membranes (pore size 0.02
      micron), some of which were coated with positively and negatively charged
      hydrogel layers. The sensors showed a stable and linear response to glucose
      concentrations > 300 mg/dL, in the presence of glucose alone in the phosphate
      buffer medium and in the presence of interferences. The interference effects of
      ascorbic acid, bilirubin, creatinine, L-cystine, glycine, uric acid, and urea on
      the amperometric signal of the sensor were studied. The PTFE membrane coated with
      the negatively charged hydrogel layer provided good protection for the enzyme
      electrode, especially in the presence of ionic interferants such as ascorbic acid
      and uric acid.

PMID- 8275144
TI  - Comparative in-vitro fluid dynamics 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 to evaluate the fluid dynamics characteristics of 12 cardiac
      bioprostheses. Pressure differences and pulsatile flow rates across the valves,
      as well as machine rates, were measured using a real-time on-line data
      acquisition system. All other valve hydrodynamic parameters were internally
      calculated. For the same pressure difference, the pulsatile flow rate was higher
      at higher pulse rates. Regurgitation fraction values were higher for valves
      tested at higher speeds. Closing volumes, however, remained fairly constant. Mean
      transvalvular pressure difference (delta p) and root mean square pulsatile flow
      rate (QRMS) under accelerated testing conditions were related according to the
      particular case of a parabolic regression through the origin of the form (type
      1), delta p = Co Q2RMS. Prosthetic valves tested in the fatigue tester presented
      in general a more effective area for flow than did valves tested in the pulse
      duplicator. Calculated discharge coefficients and performance indexes were
      accordingly higher. In both testing devices pericardial valves had higher
      effective orifice areas, discharge coefficients, and performance indexes than did
      porcine xenografts, and large valves performed more efficiently than small
      valves. Differences among regression coefficients for the same valves tested in
      both machines appeared to be significant in 100% of the cases. There were
      differences in the degrees of stenosis among valves tested in the pulse
      duplicator and in the fatigue tester. Understanding of fluid dynamics data
      obtained for undamaged valves at accelerated speeds and their relation to data
      obtained at physiologic speeds permitted the detection and quantification of
      rupture and malfunctioning of these valves without removing them from the fatigue
      tester.

PMID- 8275145
TI  - Temperature distribution beneath pediatric electrosurgical dispersive electrodes:
      a model study.
AB  - Concerns have been raised about the safety and the thermal performances of
      commercially available electrosurgical dispersive electrodes. A model system was
      designed to simulate the thermal effects observed in humans. The following
      critical factors affecting the thermal performances of pediatric electrodes were
      investigated: the intensity and duration of the applied current, the electrical
      resistivity of the test medium, the contact interface area between the electrode
      and the test medium, and the water content of the adhesive gel of the electrode.
      The maximum temperature rises (delta Tm) under the electrodes were 0.6 +/- 0.1
      degrees C, 2.8 +/- 0.2 degrees C, and 5.2 +/- 0.3 degrees C when 60 s of 1 A, 2
      A, and 3 A currents, respectively, were applied. delta Tm increased linearly with
      the increase of the duration of applied current and the resistivities of the test
      medium. When dispersive electrodes with reduced areas or reduction of water
      content of the adhesive gel of the electrodes were used, delta Tm increased with
      the areas or the water contents decreased. The currents and durations used in
      this study were in excess of those routinely used in electrosurgery. The study
      confirmed that the maximum temperature increase under the electrode is inversely
      proportional to the square of the perimeter of the electrode, rather than the
      square of the surface area. The test methods described can be used to evaluate
      the thermal performances of other electrosurgical dispersive electrodes.
      Monitoring the impedance at the interface between the dispersive electrode and
      the tissue in contact would reduce the risk of burns.

PMID- 8275146
TI  - 1993: a precarious year for critical care.

PMID- 8275147
TI  - Scoring acuity hours and costs of nursing for trauma care.
AB  - OBJECTIVE: To determine nursing resource utilization (acuity hours and dollars)
      by trauma patients based on analysis of a nursing acuity system and five trauma
      scoring systems. METHODS: Retrospective review of 448 trauma patients who
      required transport by aircraft to a level I trauma center. Values from the
      institution's automated nursing acuity system were compared with the Glasgow Coma
      Scale score, trauma score, revised trauma score, CRAMS score and injury severity
      score to obtain acuity hours and financial cost of care for trauma patients.
      RESULTS: Consistently, analysis of scores computed by five scoring instruments
      confirmed that nursing resource utilization is greatest for patients who are
      severely injured but likely to recover. For example, patients with a trauma score
      of 1 required 49 (+/- 66) mean acuity hours of care; those with a trauma score of
      8 needed 189 (+/- 229) mean acuity hours; and those with a trauma score of 16
      used 73 (+/- 120) mean acuity hours. Mean dollar costs were $980 (+/- 1293),
      $3812 (+/- 4518) and $1492 (+/- 2473), respectively. CONCLUSIONS: Nursing
      resource utilization can be determined for trauma patients by using an automated
      nursing acuity system and trauma scoring systems. Data acquired in this way
      provide a concrete basis for healthcare and reimbursement reform, for
      administrators who design nursing allocations and for nursing educators who
      prepare graduates to meet the needs of healthcare consumers.

PMID- 8275148
TI  - A collaborative practice model for critical care.
AB  - Collaborative practice behavior is a concern for healthcare providers and
      administrators, because it is associated with positive outcomes for both patients
      and staff in the intensive care unit. Despite the documented benefits derived
      from collaborative practice, it remains the exception rather than the dominant
      pattern for nurse-physician interactions. National concern for quality care and
      rising healthcare costs mandates that collaborative practice behaviors between
      nurses and physicians replace competition as the means for resolving differences.
      The purpose of this article is to describe collaborative practice, propose a
      theoretical framework for collaborative practice and discuss the development,
      implementation and evaluation of a collaborative practice model.

PMID- 8275149
TI  - A pilot study: responses to chest pain following coronary angioplasty.

PMID- 8275150
TI  - Age differences in patient recovery patterns following coronary artery bypass
      surgery.
AB  - OBJECTIVE: The purpose of this study was to determine whether physical,
      psychological and social recovery within the first 6 weeks following coronary
      artery bypass surgery varied by age. METHODS: A repeated measures design was used
      for this study. Data were collected from a convenience sample of three age groups
      of patients at the following times: prior to hospital discharge and at 1, 3 and 6
      weeks after discharge. The three age groups studied were less than 60 years, 60
      to 70 years and more than 70 years. Data were collected by interview and mail
      questionnaires. The initial sample consisted of 258 patients, of whom 184
      completed the study. Eleven instruments were used to measure recovery including
      the Sickness Impact Profile, Beck Depression Inventory, Rosenberg Self-Esteem
      scale and the Symptom Inventory. RESULTS: No significant differences were found
      among the age groups for any of the physical, psychological or social recovery
      measures. Within each age group physical, psychological and social recovery
      improved significantly over time. Although patients more than 70 years of age
      remained in the hospital significantly longer, once discharged, they did not have
      more difficulty with recovery than the other age groups. DISCUSSION: As expected,
      all age groups experienced significant improvement in recovery over time.
      CONCLUSIONS: Contrary to what past research about cardiac surgery and the elderly
      might lead one to expect, in this study, the oldest patients did not have the
      poorest recovery patterns. Persons more than 70 years had recovery patterns
      similar to those of younger age groups.

PMID- 8275151
TI  - Urinary creatinine excretion in the ICU: low excretion does not mean inadequate
      collection.
AB  - BACKGROUND: It has been assumed that a urinary creatinine excretion rate of less
      than 10 mg/kg per day means an inadequately collected urine sample. OBJECTIVE: To
      determine the frequency of a urinary creatinine excretion rate of less than 10
      mg/kg per day in intensive care unit patients with an adequately collected urine
      sample. METHOD: In a prospective study of creatinine excretion rates, 24-hour
      urine samples were evaluated for urinary creatinine in 209 critically ill
      patients with indwelling Foley catheters. Patients from three adult intensive
      care units in New York City were divided into two groups. Group 1 patients
      excreted less than 10 mg/kg per day of urinary creatinine, and group 2 patients
      excreted at least 10 mg/kg per day. Groups 1 and 2 were first evaluated by
      dividing the creatinine excretion data by actual body weight. Since actual body
      weight may overestimate body weight in the critically ill patient, data from
      groups 1 and 2 were also evaluated using lean body weight. RESULTS: Urinary
      creatinine excretion was less than 10 mg/kg per day in 36.8% of patients using
      actual body weight and 29.7% of patients adjusted for lean body weight. The
      average age of patients in group 1 was 74 +/- 17 years for both actual body
      weight and lean body weight. The average age of group 2 patients was 60 +/- 19
      years for actual body weight and 62 +/- 19 years for lean body weight. There was
      a significant difference in age between group 1 and group 2 patients for both
      actual body weight and lean body weight. The proportion of female vs male
      patients with reduced creatinine excretion was significantly greater, whether the
      actual body weight or lean body weight adjustment was used. CONCLUSIONS: A
      urinary creatinine excretion rate of less than 10 mg/kg per day occurs in about
      one third of critically ill patients, who are more likely to be elderly and
      female.

PMID- 8275152
TI  - Comparison of tidal volumes obtained by one-handed and two-handed ventilation
      techniques.
AB  - OBJECTIVES: To compare tidal volumes delivered by one- vs two-handed compressions
      of a manual resuscitation bag and assess the effects of subject characteristics
      on those tidal volumes. DESIGN: Subjects (108 healthcare providers from a 500-bed
      teaching hospital) were assigned randomly to one of two procedures: one- followed
      by two-handed compression or two- followed by one-handed compression. A 1-liter
      resuscitation bag, lung performance analyzer and Wright spirometer were used to
      measure tidal volume. Data collection occurred in a simulated situation. RESULTS:
      There was a significant difference in tidal volume delivered by one-handed (mean
      = 694 mL, SD = 111) vs two-handed compressions (mean = 827 mL, SD = 113). Hand
      size, grip strength, height and weight were correlated with tidal volumes
      generated by one-handed and two-handed procedures. No other subject
      characteristics were correlated with tidal volumes. CONCLUSIONS: Tidal volumes
      delivered by healthcare providers using one- vs two-handed compressions were
      found to be significantly different, with those delivered by two hands
      significantly greater than those delivered by one hand. Strength of hand grip was
      the best predictor of volume delivered and was more strongly correlated with
      volumes delivered by one rather than two hands.

PMID- 8275153
TI  - A stabilization period of 5 minutes is adequate when measuring pulmonary artery
      pressures after turning.
AB  - OBJECTIVE: To compare hemodynamic measurements made before turning and at 5 and
      30 minutes after turning, and to determine whether the stabilization period
      affects the difference between supine and side-lying pulmonary artery pressures.
      METHODS: This study was performed in the cardiothoracic surgical intensive care
      unit of a midwestern university hospital. The 31 postoperative open-heart
      surgical patients, 26 men and 5 women aged 41 to 76 years (64 +/- 9.3, mean +/-
      SD) with pulmonary artery catheters in place, were divided into two groups to
      compare supine to side-lying pressures and the time intervals between the
      position changes. The supine-first subjects (Group A) were placed in the supine
      position for baseline measurements and turned to either the right or left side
      lying position for the 5- and 30-minute pulmonary artery pressure measurements.
      The side-first subjects (Group B) were placed in either the right or left side
      lying position for baseline measurements and then in the supine position for the
      5- and 30-minute pulmonary artery pressure measurements. RESULTS: Pulmonary
      artery pressures, heart rate and arterial pressure were not significantly
      different at 5 and 30 minutes. Supine pulmonary artery pressures in Group A were
      not significantly different from supine pressures in Group B. Side-lying
      pulmonary artery pressures in Group A were not significantly different from side
      lying pressures in Group B. Side-lying vs supine pulmonary artery pressures were
      significantly different in both Group A and Group B. CONCLUSION: The current
      practice of turning and settling the patient, zeroing the transducer and
      proceeding to make the pulmonary artery pressure readings appears to be valid.
      The stabilization period after turning does not explain the differences found
      between side-lying and supine pulmonary artery pressures.

PMID- 8275154
TI  - Nursing care of the patient with an intravascular oxygenator.
AB  - Conventional therapy in the management of adult respiratory distress syndrome is
      often associated with an increased mortality rate. Several methods to improve
      survival in patients with severe respiratory insufficiency are under evaluation.
      One recently developed method of treatment is an implantable intravascular
      oxygenator, which provides supplemental gas exchange for failing lungs. This
      device can provide temporary ventilatory support in patients with acute,
      potentially reversible respiratory insufficiency. Reduction in ventilator
      settings such as airway pressure, oxygen concentration, positive end-expiratory
      pressure and minute volume can be achieved, decreasing the likelihood of oxygen
      toxicity and barotrauma. Success of the intravascular oxygenator in adult
      respiratory distress syndrome is dependent in part on critical care staff
      expertise. Therefore, a thorough understanding of the operation of this device
      and its role in acute respiratory failure is necessary for optimal care.

PMID- 8275155
TI  - Professional nurse caring as perceived by critically ill patients: a
      phenomenologic study.
AB  - BACKGROUND: Critically ill patients have received little attention in the caring
      literature and yet are a population for whom caring behaviors are particularly
      important. OBJECTIVES: To describe patients' perceptions of caring exhibited by
      professional nurses in a critical care unit and to describe the meaning to the
      patients of these demonstrations of caring. METHODS: We used a phenomenologic
      approach for this descriptive study, which was conducted on 13 patients
      hospitalized in a critical care unit for at least 48 hours within 48 hours of
      their transfer from the unit. We asked them to respond to two open-ended
      questions and recorded all interviews on audio tapes that were transcribed
      verbatim. RESULTS: Caring in a critical care unit is attentive, vigilant behavior
      on the part of the nurse. This vigilance embodies nurturance and incorporates
      highly skilled, technical practices, as well as basic nursing care and beyond.
      Caring is a healing process of which lifesaving actions by the nurse are a part.
      Identifying the characteristics of the individuals involved in this healing
      process was one way of describing caring. Personal attributes of nurses, family
      members, and patients themselves are important in the descriptions of the caring
      process. These attributes are incorporated into the concept of mutuality.
      CONCLUSIONS: Caring is descriptive of a mutual process in which intentions are
      joined to form a shared experience. In this mutual process, healing is an outcome
      that might otherwise be elusive.

PMID- 8275156
TI  - Radiofrequency catheter ablation for supraventricular tachycardias: Part I.
AB  - Ablative therapy in the treatment of arrhythmias is an exciting development of
      the last decade. Although direct-current, high-energy shock can be effective
      treatment for many supraventricular tachycardias, clinicians are concerned about
      potential problems associated with its use. Drug therapy for arrhythmias has been
      inadequate, ineffective, poorly tolerated and fraught with toxic or proarrhythmic
      reactions. Because of its relative technical ease, high success rate and low
      complication rate, RFCA remains the therapeutic procedure of choice for patients
      with atrioventricular nodal reentrant supraventricular tachycardia. Other
      catheter ablation techniques such as laser, cryocatheter and microwave catheter
      are still being tested.

PMID- 8275157
TI  - Flow resistance in mechanically ventilated patients with severe neurological
      injury.
AB  - In 5 mechanically ventilated patients with severe neurological injury (SNI), we
      measured the respiratory system's flow resistance (Rrs) over a range of
      inspiratory flows between 0.2 to 2 L/s, at inflation volumes (delta V) ranging
      from 0.1 to 1 L. Under baseline ventilatory conditions (V = 1 L/s; delta V = 0.95
      L), we also partitioned Rrs into airway resistance (Raw) and the additional
      resistance offered by the tissues of the lung and chest wall (delta Rrs). At all
      inflation volumes, Rrs decreased hyperbolically with increasing flow but was
      higher than in normal anesthetized paralyzed subjects (N). At V of 1 L/s and
      delta V of 0.5 L, Rrs was significantly greater in SNI than in N (7.7 +/- 1.5 v
      4.2 +/- 0.5 cm H2O/L/s; P < .01). This discrepancy was due to higher Raw in SNI.
      Indeed, at V of 1 L/s, Raw (mean +/- SEM) was significantly higher in SNI than in
      N (4.0 +/- 0.9 v 2.4 +/- 0.2 cm H2O/L/s; P < .001), whereas delta Rrs did not
      differ significantly. The increased Raw in SNI was due to the fact that these
      patients were therapeutically hyperventilated (PaCO2 = 30.4 +/- 4.2 mm Hg) and as
      a result their airways were bronchoconstricted. We conclude that in the intensive
      care unit setting, hyperventilated patients with severe neurological injury can
      not be considered to be adequate controls in terms of Rrs and Raw, because
      hypocapnia induces an increase of Raw and consequently also in Rrs (= Raw+delta
      Rrs).

PMID- 8275158
TI  - Acute renal failure in the critically ill: management by continuous veno-venous
      hemodiafiltration.
AB  - The consequences of newer techniques of continuous renal replacement therapy in
      critically ill patients are not yet fully known. The clinical and biochemical
      impact of continuous veno-venous hemodiafiltration (CVVHD) was, therefore,
      prospectively studied in 60 critically ill patients with acute renal failure.
      Prospective clinical, biochemical, and hematological data were collected from
      patients receiving CVVHD. Over the initial 24 hours of therapy, CVVHD resulted in
      a decrease in mean plasma urea from 34.5 mmol/L (95% confidence interval [CI],
      29.4 to 39.6) to 25 mmol/L (95% CI, 21.8 to 28.2). With continued CVVHD, the mean
      plasma urea reached a plateau level of 17.6 mmol/L (95% CI, 15.8 to 19.4) at 72
      hours. This degree of azotemia control was achieved with ease and essentially
      without complications during 8,360 hours of therapy despite the presence of multi
      organ failure and the aggressive administration of protein nitrogen (0.25 to 0.35
      g/kg/day). No abnormalities of serum electrolytes developed during treatment.
      Survival to intensive care discharge was 46.6% and to hospital discharge 41.6%,
      despite a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score
      at presentation of 27.7. Continuous veno-venous hemodiafiltration offers superior
      azotemia control and a safe approach to renal replacement therapy in critically
      ill patients. Its use is associated with a comparatively favorable outcome. CVVHD
      may be regarded as the treatment of choice in such patients.

PMID- 8275160
TI  - Postreperfusion syndrome: hypotension after reperfusion of the transplanted
      liver.
AB  - Sixty-nine patients undergoing liver transplantation were evaluated to elucidate
      the relationship between hypotension and physiological changes seen on
      reperfusion of the grafted liver. Measured variables included hemodynamic
      profiles, core temperature, serum potassium, ionized calcium levels, arterial
      blood-gas tensions, and acid-base state. Measurements were taken 60 minutes after
      skin incision (baseline), 5 minutes before reperfusion, and 30 seconds and 5
      minutes after reperfusion. On the basis of changes in mean arterial pressure
      (MAP) patients were divided in two groups. Group 1 (n = 49) maintained MAP
      greater than 70% and group 2 (n = 20) had MAP less than 70% of the baseline value
      for at least 1 minute within 5 minutes after reperfusion. On reperfusion, changes
      common to both groups were 27% increase in cardiac filling pressures, 23% base
      deficit, and 30% serum potassium level and a decrease of 16% in cardiac output
      and 9% in temperature. Compared with group 1, group 2 had greater decrease in
      systemic vascular resistance (SVR) (1097 +/- 868 and 741 +/- 399 dyn.s-1. cm-5,
      respectively, P < .05) and higher potassium level (4.5 +/- 0.8 and 5.3 +/- 0.8
      mmol/L, P < .05). Collectively in both groups, there was no correlation between
      MAP and physiological variables; however, there was a poor correlation with SVR
      (r = .32, P < .01). Reperfusion hypotension seen in group 2 patients correlated
      only with a decrease in systemic vascular resistance (r = .5, P < .05). Acute
      hyperkalemia, hypothermia, and acidosis do not appear to be major causes of
      reperfusion hypotension.

PMID- 8275159
TI  - Prevalence and prediction of multiple organ system failure and mortality in acute
      pancreatitis.
AB  - We studied the prevalence of multiple organ system failure (MOSF), the relations
      between age, pre-existing chronic conditions, local complications, systemic
      infection, organ system failure, and mortality in patients with acute
      pancreatitis. During the study period, 267 consecutive patients were admitted to
      a tertiary hospital with acute pancreatitis. Multivariate analyses were used to
      identify factors predictive of MOSF occurrence and mortality. Using a previously
      developed MOSF scoring system at our center, MOSF (> or = 2 organ systems) was
      found to occur in 63 (24%) of the patients. Cardiovascular, pulmonary, renal, and
      hepatic failure predominated. Advanced age (> 55 yr) and chronic disease were
      related to local complications and systemic infection (both, P < .001). Local
      complications and systemic infection occurred in 68% and 75% of patients,
      respectively. In multiple logistic regression, advanced age, chronic disease,
      local complications, and systemic infection independently contributed to the
      development of MOSF. Overall mortality was 19%. MOSF accounted for 96% of deaths;
      mortality increased from 1% to 79% in patients without and with MOSF,
      respectively. In multiple logistic regression, advanced age, chronic disease,
      local complications, failure of the cardiovascular, renal, hepatic,
      gastrointestinal, and neurological systems independently contributed to mortality
      prediction. Advanced age and prior chronic disease may reflect diminished
      physiological reserve and predispose to local complications, systemic infection,
      and MOSF. Although local complications and systemic infection are important
      predisposing factors for MOSF, a host-dependent response to unknown specific or
      nonspecific factors may have a role in the pathogenesis of the syndrome in 25% of
      patients.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275161
TI  - Infusion of ultrafiltrate from endotoxemic pigs depresses myocardial performance
      in normal pigs.
AB  - We previously showed a beneficial effect of hemofiltration on hemodynamics of
      endotoxic shock pigs. To test the hypothesis that this effect of hemofiltration
      is caused by convective removal of factors that adversely affect hemodynamics
      during endotoxemia, we infused ultrafiltrate from endotoxic shock pigs into
      healthy pigs. Their hemodynamics were compared with those of pigs who were
      infused with ultrafiltrate from healthy pigs. Twelve anesthetized and ventilated
      pigs were hemodynamically monitored for 150 minutes following the infusion of 2 L
      of ultrafiltrate from 12 donor pigs. The acceptor pigs were randomly divided into
      two groups; group 1 received ultrafiltrate from pigs who were hemofiltered after
      the infusion of 0.5 mg/kg endotoxin over 30 minutes; group 2 served as a control
      group, receiving ultrafiltrate from healthy donor pigs. Group 1 showed a decrease
      in mean arterial pressure of 28 +/- 7 mm Hg (mean +/- SEM) versus an increase of
      17 +/- 3 mm Hg in group 2 (P < 0.4). Mean pulmonary artery pressure increased
      more in group 1 than in group 2 (9 +/- 2 mm Hg versus 1 +/- 1 mm Hg, P < .04).
      The decrease in cardiac output in group 1 was greater than in group 2 (3.3 +/-
      0.2 L/min v 0.3 +/- 0.3 L/min, P < .02) and was due to a decrease in stroke
      volume. The decrease in right ventricular ejection fraction was also greater
      (0.15 +/- 0.02 v 0.01 +/- 0.00, P < .01). Systemic vascular resistance, right
      atrial pressure, right ventricular end-diastolic volume, pulmonary wedge pressure
      and heart rate did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275162
TI  - The ethics of letting go.
AB  - Emphasis in medical training is laid on therapeutic approaches that prolong life
      at all costs. This training is reinforced by current medical practices in the
      United States and by an ever-expanding medical technology, such that it becomes
      difficult, if not impossible, to "let the patient go." In response, individuals
      promote the "right-to-die" and euthanasia, so that patients may maintain their
      human dignity during the dying process. A more rational and nonpolarized approach
      to this issue would be to strive for the preservation of human function, not
      physiological function alone. The goal would include helping patients advance
      their life plans and values. On this basis, therapies can be withheld and
      withdrawn when they no longer reflect these goals. Caution regarding potential
      abuses of this approach need to be raised, however, when considering care for the
      very vulnerable of society. In that regard, therapeutic goals directed at
      maintaining human function need to be developed in parallel with global societal
      values regarding quality of life issues.

PMID- 8275163
TI  - Deciding to terminate treatment: a practical guide for physicians.
AB  - Providing house officers and practicing physicians with annotated, concise,
      practical guidelines for decisions to terminate treatment is the objective of
      this report. The study selection and data extraction focused on statutes,
      regulations, court decisions, medicolegal analyses, clinical studies, and
      position papers addressing termination-of-treatment issues. To foster a
      systematic approach, we developed a laminated, pocket-sized card containing a
      series of questions to be asked by any physician confronted with termination-of
      treatment decisions. Systematic identification and deliberate assessment of (1)
      brain death; (2) the nature, extent, cause, prognosis, and reversibility of
      impairment; (3) the type of treatment to be withheld or withdrawn; (4) the
      futility of any proposed intervention; (5) the capacity of the patient for health
      care decision-making; (6) the evidence of patient's wishes; (7) the proper roles
      of family members, surrogate decision makers, and other health professionals (eg,
      ethics committees); and (8) applicable policies, ethics, laws, and potential
      conflicts of interest will enhance efficiency and add value to the decision
      making process at the end of life.

PMID- 8275164
TI  - Controlling health care: from economic incentives to micro-clinical regulation.

PMID- 8275165
TI  - Clinical importance, statistical significance and the assessment of economic and
      quality-of-life outcomes.
AB  - The assessment of economic and quality-of-life outcomes of health care
      interventions is moving into a new era, with such assessments increasingly being
      made within the context of controlled clinical trials. Traditionally the
      measurement of many variables in economic evaluations, particularly costs, has
      been deterministic. In the context of clinical trials the measurement of
      variables is stochastic, with the standard principles of statistical inference
      being applied to analyse differences between treatments in terms of
      effectiveness. Economists participating in clinical research are therefore being
      called upon to specify the sample size for the economic component of the
      evaluation and to undertake statistical tests for differences in cost or cost
      effectiveness. This paper discusses the current methodological issues surrounding
      stochastic measurement in clinical trials, discusses the additional issues raised
      by the assessment of economic and quality-of-life outcomes and specifies the
      challenges facing economists if they are to answer the questions now being posed
      about economic analysis by statisticians and clinical researchers. It is
      concluded that application of the standard principles of statistical inference to
      economic data is not straightforward and will require value judgements to be made
      about statistical significance and economic importance, which may differ from
      those already made in purely clinical studies.

PMID- 8275166
TI  - The SF-36 health survey questionnaire--a tool for economists.

PMID- 8275167
TI  - The RAND 36-Item Health Survey 1.0.
AB  - Recently, Ware and Sherbourne published a new short-form health survey, the MOS
      36-Item Short-Form Health Survey (SF-36), consisting of 36 items included in long
      form measures developed for the Medical Outcomes Study. The SF-36 taps eight
      health concepts: physical functioning, bodily pain, role limitations due to
      physical health problems, role limitations due to personal or emotional problems,
      general mental health, social functioning, energy/fatigue, and general health
      perceptions. It also includes a single item that provides an indication of
      perceived change in health. The SF-36 items and scoring rules are distributed by
      MOS Trust, Inc. Strict adherence to item wording and scoring recommendations is
      required in order to use the SF-36 trademark. The RAND 36-Item Health Survey 1.0
      (distributed by RAND) includes the same items as those in the SF-36, but the
      recommended scoring algorithm is somewhat different from that of the SF-36.
      Scoring differences are discussed here and new T-scores are presented for the 8
      multi-item scales and two factor analytically-derived physical and mental health
      composite scores.

PMID- 8275168
TI  - Convergent validity of two measures of the quality of life.
AB  - In the paper, a test of convergent validity is undertaken for two methods of
      quality of life assessment, one based on a shortened version of the Health
      Measurement Questionnaire and the other based on professional clinical judgement.
      The Nottingham Health Profile is used as the comparator, and the data derive from
      a sample of colorectal cancer patients. Criteria for convergent validity are
      established and both methods yield outcomes broadly consistent with such
      criteria.

PMID- 8275169
TI  - Generalizability of valuations on health states collected with the EuroQolc
      questionnaire.
AB  - PROBLEM: Non-response and non-usable response were found in population surveys on
      valuation of health states. If non-response is selective regarding valuations,
      then generalization of the resulting values to the whole survey population is not
      permitted. This could limit the use of empirical utility values in resource
      allocation in health care. METHODS: Response behaviour of a sample of 1400 from
      the Dutch general population to the mailed EuroQolc-questionnaire was analyzed by
      four methods. I. Phoning resolute non-respondents; II. comparison of zip code
      characteristics of respondents and non-respondents (because individual data on
      background characteristics were not available for the non-respondents); III.
      analysis of response over time (wave-analysis); IV: comparison of background
      variables of successful (less than two valuations missing) and unsuccessful
      respondents, combined with analysis of the effect of these background variables
      on valuations. RESULTS: No indications for selective non-response were found,
      although the phenomenon appeared hard to investigate. The successful response
      came from a slightly younger and better educated subsample. However, a general
      influence of age and educational level on valuations could not be shown. This
      finding is consistent with the literature. CONCLUSION: Although the existence of
      selective non-response cannot be excluded, its relevance can be considered to be
      small. This finding is encouraging for the use of empirical utility values in
      allocative decisions.

PMID- 8275171
TI  - Time preferences for health gains: an empirical investigation.
AB  - The purpose of this study was to elicit the implied discount rates to be used in
      economic evaluations of health care programmes. The paper presents results from
      two Norwegian surveys in which a random sample of the population and a sample of
      health planners were asked to prioritise between alternative health care
      programmes, and make trade-offs between future health gains and more immediate
      gains. The questionnaire had four hypothetical choice situations; two for life
      saving and two for health improvement.

PMID- 8275170
TI  - A cost function analysis of residential services for adults with a learning
      disability.
AB  - Successive UK governments have pursued a policy of community care for people with
      learning disabilities which, in the past ten years, has led to a marked change in
      the nature of residential provision. Research evidence on the costs and quality
      of alternative forms of community provision is inconclusive and contradictory. It
      is therefore timely to consider whether or not community residential facilities
      have delivered the expected quality of service at appropriate cost. The paper
      presents the results of a cost function analysis of a random stratified sample of
      staffed community facilities in England excluding London. Both costs and quality
      of care were found to vary greatly amongst community residential facilities. The
      most important factors explaining differences in cost were case-mix factors
      relating to client age, dependency and length of stay. Facility characteristics
      such as the type of building, the internal layout and the structural quality were
      not significant. Quality of service measures such as the extent to which care
      regimes were client orientated and made use of local community services were
      positively and significantly associated with costs. Type of provider had no
      impact on costs independent of differences in case-mix and quality of care with
      the exception of the private for profit sector which appeared less expensive than
      other agencies. The shortcomings of the methods and implications of these
      findings for policy makers are discussed.

PMID- 8275172
TI  - Expected social utility of life time in the presence of a chronic disease.
AB  - Interventive action aimed at reducing the incidence of an irreversible chronic
      noncommunicable disease in a population has various effects. Hopefully, it
      increases total longevity in the population and it causes the disease to develop
      later in time in a smaller portion of the population. In this paper a statistical
      model is built by which these effects can be estimated. A three dimensional
      probability density function that underlies this model is changed by the
      interventive action. It is shown how a three dimensional utility function can be
      defined to appropriately judge this change.

PMID- 8275173
TI  - Have procompetitive changes altered hospital provision of indigent care?
AB  - In the past decade alone there have been numerous changes in the financial and
      competitive environment of hospitals in the United States. Some examples include
      the advent of Medicare's Prospective Payment System, growth in managed care
      options, relaxation of states' Certificate of Need (CON) regulations, and court
      cases questioning the tax-exempt status of nonprofit hospitals. In this paper we
      attempt to reveal how hospitals alter their provision of care to the poor in a
      more cost conscious and competitive environment. Using hospital data from the
      State of California for the fiscal years ending in 1983 and 1987, estimates
      explaining uncompensated care commitments are presented. In particular, this
      study illustrates how hospitals under different ownership control varied their
      provision of uncompensated care over the period studied on average and by
      profitability level. Other factors, such as hospital location, teaching status,
      medicare patient load, and contractual adjustments, are also included in the
      analysis. A number of interesting trends are detected. Moreover, the results are
      found to be compatible with a quid pro quo hypothesis which states that hospital
      regulators reward large uncompensated care providers with profitable CON
      licenses.

PMID- 8275174
TI  - Comparing steady counterflow separation with differential chromatography.
AB  - Separation of closely related solutes by steady solid-fluid counterflow is
      compared with differential separation in a fixed chromatographic bed. Analogous
      expressions for exit concentration and mean residence time in the two systems are
      presented. A counterpart to chromatographic resolution is derived for binary
      steady counterflow separations. Estimated counterflow savings in product
      concentration dilution, solvent volume requirement and solid-phase volume
      requirement obtained with these expressions relative to comparable
      chromatographic operations are compared with experimental results from
      adsorptive, simulated moving beds. Analysis of a size-exclusion protein
      separation suggests counterflow substantially decreases solvent and resin usage
      relative to conventional, batch operation.

PMID- 8275175
TI  - Chiral ion-exchange chromatography. Correlation between solute retention and a
      theoretical ion-exchange model using imprinted polymers.
AB  - Mobile phase effects were studied in the separation of D- and L-phenylalanine
      anilide (D,L-PA) on an imprinted chiral stationary phase (CSP). Using an aqueous
      organic mobile phase, an improved column performance was seen, reflected in a two
      fold decrease in the reduced plate height and an almost doubling of the
      resolution as compared to when a pure organic mobile phase was used. A strong
      dependence of retention (k') and enantiomer selectivity (alpha) on mobile phase
      pH was observed. k' reached a maximum at a pH close to the pKa value of the
      solute and alpha was high at low pH value but decreased when pH exceeded the
      solute pKa. Potentiometric titration data allowed estimation of the state of
      protonation of both the carboxylic acid containing CSP and the amino group
      containing solutes. The data are analyzed using a simple cation-exchange model to
      allow simulation of the retention as a function of mobile phase pH. The close
      agreement between the simulated and experimental curves for retention versus pH
      suggests that a simple cation-exchange mechanism controls the retention in this
      system. Moreover, the slightly lower average pKa of the imprinted polymer
      compared to that of a corresponding blank polymer explains the high selectivity
      seen at low pH values. Based on these findings, a model describing the events
      controlling binding and selectivity as a function of pH is proposed.

PMID- 8275176
TI  - Rapid capillary gel electrophoresis of proteins.
AB  - The rapid separation of sodium dodecyl sulphate-protein complexes according to
      their molecular masses (M(r)) by capillary gel electrophoresis is described.
      Using commercial equipment, standard proteins with M(r) in the range 29,000
      97,400 were resolved to the baseline in less than 2 min by utilizing a separation
      distance of 7 cm. A linear relationship between migration time and log M(r) was
      found and rapid determination of the molecular mass of light and heavy chains of
      human immunoglobulin G is reported. The results are compared with applications
      using longer separation distances, showing that rapid and efficient analysis and
      adequate resolution can be obtained by using short separation distances.

PMID- 8275177
TI  - Characterization and application of strong ion-exchange membrane adsorbers as
      stationary phases in high-performance liquid chromatography of proteins.
AB  - Filtration membranes carrying strong cation- or anion-exchange groups on their
      surface were evaluated for their potential as membrane adsorber stationary phases
      in the high-performance liquid chromatography of proteins. The membranes are
      commercially available and can be obtained inserted into ready-to-use filter
      holders. Owing to their thinness (170-190 microns), the pressure drop of the
      membranes is extremely low. Flow-rates of up to 65 ml min-1 per unit became thus
      possible. The low pressure drop of a single membrane layer also permitted an
      effortless scaling up, as a stack of several membranes or filter units could be
      used, if necessary. Sample distribution, protein binding capacity, elution
      conditions, separation efficiency and recovery were investigated as a function of
      the flow-rate. The time required for the separation of certain protein mixtures
      could be reduced to less than 1 min. Appropriate conditions were defined for the
      separation of human serum and for the isolation of subtilisin Carlsberg and beta
      galactosidase from cell culture supernatants.

PMID- 8275178
TI  - Resolution of chiral cannabinoids on amylose tris(3,5-dimethylphenylcarbamate)
      chiral stationary phase: effects of structural features and mobile phase
      additives.
AB  - The separation of six pairs of chiral cannabinoids was achieved using a
      dimethylphenylcarbamate derivative of amylose, immobilized on silica gel
      (ChiralPak AD, Daicel), using 2-propanol and ethanol as the modifiers of n-hexane
      in the mobile phase. Good separation was achieved for most of the solutes in both
      solvent systems under various conditions. The chromatographic parameters of
      various cannabinoids in the two solvent systems were determined. The pairs differ
      from each other in small structural features such as the degree of saturation,
      position of a double bond and closure of a pyran ring. Therefore, a comparative
      study could give some clues regarding the mechanism of discrimination between the
      enantiomeric pairs on the chiral stationary phase. Preliminary measurements of
      limit of determination showed that it was possible to assess 99.9% enantiomeric
      purity of the cannabinoids, owing to the high efficiency of the separation.
      Enantiomers of two monoterpenes, used as intermediates or as starting materials
      in the chiral synthesis of cannabinoids, were also separated, hence the described
      procedure is capable of assessing whether the chiral centres in the molecules
      were sustained throughout the synthetic procedures.

PMID- 8275179
TI  - Sensitive and selective liquid chromatographic postcolumn reaction detection
      system for biotin and biocytin using a homogeneous fluorophore-linked assay.
AB  - A homogeneous fluorophore-linked assay was used to develop a postcolumn reaction
      detection system for high-performance liquid chromatography (HPLC). Biotin and
      biocytin were chosen as the model analytes. The effluent from the HPLC column was
      merged with a reagent stream containing avidin that was labeled with fluorescein
      isothiocyanate (avidin-FITC). The binding of the separated analytes by the
      labeled avidin was accompanied by an enhancement of the fluorescence intensity at
      520 nm. This increase in fluorescence was proportional to the concentration of
      the analytes and constituted the analytical signal. The procedure was optimized
      with respect to the reagent concentration and the flow-rate of the reagent
      solution. Analytical characteristics of the method were determined. The procedure
      was highly selective for biotin and its derivatives. The detection limits for
      biotin and biocytin were 89 and 94 pg, respectively, for 20-microliters
      injections. The developed postcolumn reaction detection system was validated by
      determining biotin in a liquid vitamin preparation and a horse-feed supplement.

PMID- 8275180
TI  - Speciation of inorganic and organotin compounds in biological samples by liquid
      chromatography with inductively coupled plasma mass spectrometric detection.
AB  - This paper describes the effect of inorganic tin chloride on the separation of
      trimethyl-, tributyl- and triphenyltin-chlorides by reversed-phase ion-pair high
      performance liquid chromatography with detection by inductively coupled plasma
      mass spectrometry. The detection limits are 1.6 pg, 1.5 pg and 2.3 pg as tin for
      trimethyltin, tributyltin and triphenyltin, respectively. The relative standard
      deviation for ten injections of 20 ng of the tin compounds was less than 5%.
      Inorganic tin was held strongly on the columns used, to a greater extent on the
      silica column compared to the polymer column. Extraction and determination of
      tributyltin and triphenyltin as chlorides in fish tissue (certified reference
      material) and tuna fish (grocery store) were performed. The recovery study from
      fish tissue showed an efficiency of over 90% for both tributyltin and
      triphenyltin and over 60% recovery for spiked tuna.

PMID- 8275181
TI  - A frontier of family medicine. The revival of obstetrics.

PMID- 8275182
TI  - The Munchhausen of Munchausen syndrome. A historical perspective.

PMID- 8275183
TI  - Clinical follow-up of cervical sampling with the Ayre spatula and Zelsmyr
      cytobrush.
AB  - OBJECTIVE: To determine if cervical smears obtained with an Ayre spatula and a
      cytobrush are better detectors of atypia and dysplasia than the modified Ayre
      spatula alone, as determined by a 2-year clinical follow-up study. METHOD: Paired
      cervical samples were obtained, one using a modified Ayre spatula and the other a
      cytobrush. In those smears with any abnormality, follow-up after 2 years
      documented subsequent cytologic and/or histologic diagnosis. The statistical
      relationship between the screening tests and follow-up cytologic diagnosis was
      investigated. SETTING: Seven hundred ninety-two women, aged 18 years and older,
      who presented to a family practice residency clinic for Papanicolaou tests.
      RESULTS: The correlation coefficient for the diagnoses obtained using the
      modified Ayre spatula and the clinical follow-up was .40 (P = .0008), while the
      correlation coefficient between the cytobrush samples and the clinical follow-up
      diagnoses was .25 (P = .04). The kappa statistics indicate statistically
      significant concordance only between the spatula and the follow-up diagnoses.
      CONCLUSIONS: Cervical smears obtained with a modified Ayre spatula correlated
      significantly with the follow-up diagnoses. As cervical sampling tools emerge,
      they need to be evaluated on the basis of accurate identification of significant
      clinical disease, not only on the basis of obtaining endocervical cells to avoid
      unnecessary repetition of screening tests and diagnostic workups.

PMID- 8275184
TI  - Predicting exercise and smoking behaviors in diabetic and hypertensive patients.
      Age, race, sex, and psychological factors.
AB  - OBJECTIVE: To predict exercise and smoking behaviors in primary care patients
      with chronic diseases (insulin-dependent diabetes mellitus [IDDM], non-insulin
      dependent diabetes mellitus [NIDDM], and hypertension) using standardized
      measures of stress, affect, and family function. DESIGN: Survey by a self
      administered health risk appraisal and the Family APGAR Scale (measuring family
      function), the Brief Encounter Psychosocial Instrument (measuring coping with
      psychological stress), and the Affect Balance Scale (measuring positive and
      negative affect). SETTINGS: Large family practice center, university medical
      center pediatrics clinic, and community health center. PARTICIPANTS: Volunteers
      meeting World Health Organization criteria for IDDM (n = 83) or NIDDM (n = 322),
      and volunteers with documented hypertension (n = 140). MAIN OUTCOME MEASURES:
      Exercise levels at or above 2510 kJ/wk; smoking status; and number of cigarettes
      consumed per day. RESULTS: Smoking status in all groups was lower than that
      measured nationally. Stepwise logistic regression showed a correlation between
      positive affect and higher exercise levels among patients with IDDM and NIDDM,
      but lower levels among hypertensives. Psychological stress correlated with
      current smoking among patients with IDDM. In pooled models, whites were much more
      likely than blacks to exercise at higher levels and to be former or nonsmokers;
      however, among smokers, whites consumed more cigarettes per day. Among smokers
      with IDDM, males were much more likely to be moderate to heavy smokers.
      CONCLUSIONS: Among patients with IDDM, NIDDM, and hypertension, psychosocial
      stress, affect, age, race, and sex differentially predict exercise and smoking
      behaviors. The lower-than-national prevalence of smoking in these groups may
      indicate increased responsiveness to the stop-smoking message. Black diabetic and
      hypertensive patients, in particular, may require increased health promotion
      efforts.

PMID- 8275185
TI  - Primary care of patients with human immunodeficiency virus infection. The
      physician's perspective.
AB  - OBJECTIVE: To examine physicians' perceptions, motivations, and influences on
      their willingness to care for patients with human immunodeficiency virus (HIV).
      DESIGN: Interviews with 30 physicians. Qualitative content and narrative analyses
      were performed. SETTINGS: Community-based primary care practices in six moderate
      sized cities in the northeastern United States with at least a moderate incidence
      or prevalence of reported acquired immunodeficiency syndrome cases. PARTICIPANTS:
      Thirty community-based primary care physicians who had cared for at least two
      patients with HIV during the previous 2 years. MAIN OUTCOME MEASURE: Qualitative
      study designed to provide rich descriptive data. RESULTS: Care of patients with
      HIV was regarded as part of the scope of primary care, and was perceived to be
      similar to the care of patients with other chronic illnesses. Many physicians
      were motivated by personal rewards in taking care of patients, intellectual
      challenge, and desire to serve the underserved. Most believed that practicing
      physicians have an ethical obligation to care for all patients, regardless of
      diagnosis. No one "type" of physician could be identified who provides care to
      patients with HIV. CONCLUSIONS: Primary care physicians can apply their skills in
      the management of other chronic diseases to the care of patients with HIV.
      Practicing physicians can find caring for patients with HIV rewarding,
      stimulating, and enjoyable. Educational programs for physicians need to emphasize
      psychosocial aspects of HIV care. In addition, physicians need opportunities to
      recognize and deal effectively with their own emotional responses to the care of
      patients with HIV.

PMID- 8275186
TI  - Immobility in the aged.
AB  - Bed rest has historically been used therapeutically in the management of many
      chronic maladies prevalent in elderly persons. Unfortunately, the deleterious
      consequences of immobility predispose elderly persons to significant functional
      decline and reduced quality of life. Prolonged inactivity reduces the physiologic
      reserve of most organ systems, particularly the musculoskeletal and
      cardiopulmonary systems. Consequently, muscle weakness, contracture formation,
      postural hypotension, and thrombogenic events are common in bed-bound patients.
      Fortunately, contemporary studies have dispelled the myth that inactivity fosters
      healing and have suggested techniques that may prevent immobility-induced
      dysfunction and ensure beneficial outcome in fragile and aging populations.

PMID- 8275187
TI  - Unproven diet therapies in the treatment of the chronic fatigue syndrome.
AB  - This report is a review of the unproven diet therapies recommended for
      individuals with chronic fatigue syndrome (CFS). Diet therapies promoted for the
      relief of CFS symptoms by the authors of five CSF self-help books were evaluated
      on the basis of nutritional adequacy and scientific rationale. Unproven diet
      therapies for patients with CFS include megavitamin/mineral supplements; royal
      jelly and other dietary supplements; and elimination, avoidance, and rotation
      diets. Claims that these therapies relieve CFS symptoms and promote recovery are
      anecdotal and have not been substantiated by clinical research. The yeast
      avoidance and sugar-free diets, both promoted to combat Candida albicans
      overgrowth, are of questionable value in treating patients with CFS. The rotation
      diet is not balanced and does not meet the current recommended dietary intake
      levels. Diet strategies that call for the avoidance of food additives,
      preservatives, sweeteners, and other ingredients are not supported by available
      evidence and are not practical for patients with CFS. A diet plan for patients
      with CFS should be based on sound nutritional principles and common sense. Until
      the results of studies demonstrating the benefits of particular diet therapies in
      the management of CFS are available, patients with CFS are advised to eat a
      varied diet selected from among and within the basic food groups to ensure an
      adequate nutrient intake and to reach and maintain a reasonable body weight.

PMID- 8275188
TI  - Hepatic abscess presenting as severe fatigue and anemia.
AB  - We describe a 54-year-old woman who had severe anemia as the initial presentation
      of a pyogenic hepatic abscess. She was afebrile and denied any gastrointestinal
      symptoms other than anorexia. We discovered her hepatic abscess when we evaluated
      her for an occult malignancy as the cause of her anemia. She was treated with
      percutaneous drainage of her abscess and parenteral antibiotic therapy. We
      searched MEDLINE, a computerized database, to find other patients whose hepatic
      abscesses presented as anemia. Although mild anemia is a common accompaniment of
      pyogenic hepatic abscesses, we found no reports of patients who presented with
      fatigue and anemia without any of the more common symptoms of hepatic abscess,
      such as fever, right upper quadrant pain, malaise, or nausea. We conclude that
      anemia without fever or abdominal symptoms is a rare presentation of pyogenic
      hepatic abscess.

PMID- 8275189
TI  - Guidelines for the medical management of the home-care patient. American Medical
      Association Home Care Advisory Panel.
AB  - Increasing numbers of patients of all ages are receiving needed health care
      services in non-institutional settings. Acute, subacute, rehabilitative,
      preventive, long-term, and hospice services are provided in the home under the
      physician's supervision. The safe and appropriate treatment of these patients
      involves the physician in a team effort as most home care is provided by nurses,
      other allied health professionals, and family members. The guidelines cover such
      areas as the role of the physician; the physician-patient relationship; the
      elements of medical management in home care, including the evaluation/assessment
      process, the selection of the interdisciplinary team, and the development of the
      care plan; patient's rights and responsibilities; the coordination of care; and
      the use of community resources.

PMID- 8275190
TI  - Food safety. Federal inspection programs. Council on Scientific Affairs, American
      Medical Association.
AB  - Concern about the safety of the US food supply has stimulated criticism of the
      present system for assuring safe food in American markets. This report was
      prepared in response to resolutions introduced at the American Medical
      Association House of Delegates' December 1990 Interim Meeting. The resolutions
      requested the AMA to study the plans and procedures needed to improve the federal
      inspection of meat, poultry, and shellfish. To put these issues into perspective,
      an overview of food safety is presented. This report is not intended, however, to
      be a broad review of the Food and Drug Administration's and the US Department of
      Agriculture's responsibilities for food safety.

PMID- 8275191
TI  - A prospective study of diet, smoking, and lower urinary tract cancer.
AB  - The association of diet and smoking with bladder cancer was investigated in a
      cohort study conducted in Hawaii. The study included 7995 Japanese-American men
      who were born between 1900 and 1919, and were examined from 1965 to 1968. After
      22 years of follow-up, 96 incident cases of bladder cancer were diagnosed.
      Current cigarette smokers had a 2.9-fold risk of bladder cancer, compared with
      nonsmokers. A direct dose-response relation was observed, based on pack-years of
      cigarette smoking. Consumption of fruit was inversely associated with the risk of
      bladder cancer (P = 0.038). The relative risk was 0.6 among subjects who had the
      most frequent (> or = 5 times/wk) intake of fruits compared to those with the
      least intake (< or = 1 time/wk). A weaker inverse association with milk intake
      was also observed (P = 0.07). Frequent consumption of fried vegetables, pickles,
      or coffee increased the risk of bladder cancer, but none of these foods showed a
      significant dose-response relationship. There was no association of other
      selected foods, alcohol, total calories, protein, fat, or carbohydrates with
      bladder cancer risk.

PMID- 8275192
TI  - Vitamin A, Vitamin E or beta-carotene status and hepatitis B-related
      hepatocellular carcinoma.
AB  - A case-control study was carried out in 59 patients with newly diagnosed
      hepatocellular carcinoma and 101 control subjects, who were all male hepatitis B
      carriers. The odds ratios of hepatocellular carcinoma occurring among hepatitis B
      carriers in the lowest quartile and those highest quartile of dietary and serum
      status were 5.3 (1.9 to 15.0) and 86.9 (20.0 to 377.2), respectively. The odds
      ratios for hepatitis B carriers in the lowest quartile and those in the highest
      quartile of dietary and serum beta-carotene status were 1.7 (0.7 to 4.1) and 5.0
      (1.9 to 13.2). Vitamin E status did not differ in case patients and control
      subjects. Low education level, heavy consumption of alcohol, and smoking status
      were also associated with increased odds of hepatocellular carcinoma. Serum
      retinol, positively associated with dietary retinol, demonstrated an independent
      effect on hepatocellular carcinoma. This effect may reflect changes in the
      physiologic condition of the patients at the time of entering the hospital.

PMID- 8275193
TI  - Chemoprevention of oral leukoplakia and chronic esophagitis in an area of high
      incidence of oral and esophageal cancer.
AB  - This intervention trial carried out in Uzbekistan (former USSR) in an area with a
      high incidence of oral and esophageal cancer involved random allocation of 532
      men, 50 to 69 years old, with oral leukoplakia and/or chronic esophagitis to one
      of four arms in a double-blind, two-by-two factorial design, with active arms
      defined by the administration of (a) riboflavin; (b) a combination of retinol,
      beta-carotene, and vitamin E; or (c) both. Weekly doses were 100,000 IU of
      retinol, 80 mg of vitamin E, and 80 mg of riboflavin. The dose of beta-carotene
      was 40 mg/d. Men in the trial were followed for 20 months after randomization.
      The aim of the trial was to determine whether treatment with these vitamins or
      their combination could affect the prevalence of oral leukoplakia and/or protect
      against progression of oral leukoplakia and esophagitis, conditions considered to
      be precursors of cancer of the mouth and esophagus. A significant decrease in the
      prevalence odds ratio (OR) of oral leukoplakia was observed after 6 months of
      treatment in men receiving retinol, beta-carotene, and vitamin E (OR = 0.62; 95%
      confidence interval (CI): 0.39 to 0.98). After 20 months of treatment, no effect
      of vitamin supplementation was seen when the changes in chronic esophagitis were
      compared in the four different treatment groups, although the risk of progression
      of chronic esophagitis was lower in the subjects allocated to receive retinol,
      beta-carotene and vitamin E (OR = 0.65; 95% CI: 0.29 to 1.48) A secondary
      analysis not based on the randomized design revealed a decrease in the prevalence
      of oral leukoplakia in men with medium (OR = 0.45; 95% CI: 0.21 to 0.96) and high
      (OR = 0.59; 95% CI: 0.29 to 1.20) blood concentrations of beta-carotene after 20
      months of treatment. Risk of progression of chronic esophagitis was also lower in
      men with a high blood concentration of beta-carotene, odds ratios being 0.30 (95%
      CI: 0.10 to 0.89) and 0.49 (95% CI: 0.15 to 1.58) for medium and high levels,
      respectively. A decrease in risk, also statistically not significant, was
      observed for high vitamin E levels (OR = 0.39; 95% CI: 0.14 to 1.10). These
      results were based on levels of vitamins in blood drawn after 20 months of
      treatment.

PMID- 8275194
TI  - Diet and melanoma. An exploratory case-control study.
AB  - This population-based case-control study contrasted nutrient intakes of 41 women
      with cutaneous malignant melanoma to those of 297 women sampled from the same
      community (Brisbane, Australia). Diet was assessed by a comprehensive food
      frequency questionnaire. The strong inverse relation we observed between high
      intakes of polyunsaturated fatty acids and melanoma (P < 0.01) adds sufficient
      weight to prior findings for this persisting causal hypothesis to be abandoned. A
      relatively strong association with alcohol was observed: Women drinking 20 g or
      more (two or more drinks) daily had 2.5 (odds ratio) times the risk of melanoma
      as nondrinkers (95% confidence interval, 0.87 to 7.4). However, previous data are
      inconsistent. With regard to potential protective factors, our data fit with
      prior speculation that antioxidants (beta-carotene and vitamin E), zinc, and iron
      warrant further investigation. The nonsignificant (P = 0.18) 40% reduction in
      risk seen for those eating the most fish (> or = 15 g daily versus < 5 g)
      suggests the effects of marine oils and omega-3 fatty acids may deserve specific
      attention.

PMID- 8275195
TI  - Cigarettes, alcohol, coffee, and caffeine as risk factors for colorectal
      adenomatous polyps.
AB  - The possible association of colorectal adenomatous polyps, a precursor lesion for
      colorectal cancer, with cigarette smoking, alcohol consumption, and coffee and
      caffeine consumption was investigated in a case-control study. Between April 1986
      and March 1988, 271 cases of patients with pathologically confirmed incident
      colorectal adenomatous polyps and 457 control subjects were collected from three
      colonoscopy practices in New York City. Information on exposure was obtained by
      structured interviews. After adjustment of age, statistically significant odds
      ratios (highest-lowest quartile) were found for cigarette smoking in males (2.2;
      95% confidence interval (CI), 1.2 to 3.8) and coffee consumption in females
      (2.0%; 95% CI, 1.0 to 3.9). No significant associations were obtained for
      cigarette smoking in females, for coffee consumption in males, or for alcohol or
      caffeine consumption. After adjustments for alcohol, coffee, and caffeine
      consumption, the association of adenomas with cigarette smoking remained in males
      and significant associations were also observed in subcategory analysis for both
      left-side and right-side adenomatous polyps. Adjustment for cigarette smoking
      eliminated the association between colorectal adenomatous polyps and coffee
      consumption in females. Cigarette smoking appears to be a significant risk factor
      for colorectal adenomatous polyps in males.

PMID- 8275196
TI  - Alcohol and blood pressure. The effects of age. Findings from the Italian Nine
      Communities Study. The Research Group ATS-RF2 of the Italian National Research
      Council.
AB  - This report analyzes the role age in the association between alcohol consumption
      and blood pressure in a large sample (n = 6165) of Italian men and women, aged 20
      to 59 years, who participated in a multicenter study on risk factors for
      arteriosclerosis. Age-stratified analysis indicated that both men and women aged
      50 to 59 years showed the strongest positive association between alcohol
      consumption and blood pressure. While in men the association between systolic
      blood pressure and alcohol consumption increased linearly with age, in women the
      association between systolic blood pressure and alcohol increased sharply in the
      oldest (50 to 59 year) age group.

PMID- 8275197
TI  - Coffee and serum lipids: findings from the Olivetti Heart Study.
AB  - The relationship between coffee consumption and blood lipids was analyzed in a
      sample of 900 male workers of southern Italy participating in the Olivetti Heart
      Study. In the univariate analysis, coffee drinkers (n = 856) had higher values
      for body mass index (P < or = 0.05) and number of cigarettes smoked per day (P <
      or = 0.001) and lower levels of serum high-density-lipoprotein cholesterol (P <
      or = 0.05), compared to noncoffee drinkers (n = 44). In addition, coffee
      consumption (cups/d) was positively related to serum triglyceride levels (r =
      0.105, P < or = 0.01) and cigarette smoking (r = 0.491, P < or = 0.01), and was
      inversely related to age (r = -0.122, P < or = 0.01). After multivariate
      adjustment, coffee consumption remained significantly related to age, cigarette
      smoking, and body mass index (data not shown). After stratification for smoking
      status, a significant positive linear trend between coffee consumption and serum
      total cholesterol was observed only in smokers. No significant trend was observed
      for serum triglycerides and high-density-lipoprotein cholesterol with coffee
      intake according to smoking status. This finding suggests that the relationship
      between coffee consumption and serum total cholesterol may change with the
      smoking status.

PMID- 8275198
TI  - A longitudinal study of the determinants of bone mass in Chinese women aged 21 to
      40. I. Baseline association of anthropometric measurements with bone mineral
      density.
AB  - The bone mineral density of the lumbar spine (L2 to L4) and neck of the femur of
      293 Chinese women aged 21 to 40 years was measured using a dual x-ray
      densitometer. The participants were recruited from subjects registered with the
      University Family Medicine Clinic in Hong Kong. Our cross-sectional data showed
      that maximal bone mass occurs in the early 30s. Both the spine and hip bone
      masses were observed to decline at a rate of around 1% per annum from the early
      30s onward. Body weight, lean body mass, and body fatness were significantly
      associated with the mineral density of the spinal and femoral bones after or
      around the attainment of peak bone mass, while no correlation of these data was
      observed in the younger age group (20 to 28 years). Other factors may play a more
      important role than body mass in influencing bone mineral density before
      attainment of peak bone mass.

PMID- 8275199
TI  - An epidemiologic study of osteoporosis in Taiwan.
AB  - In 1989, a cross-sectional study was carried out in Taiwan to understand the
      distribution of bone mineral density (BMD) in the lumbar spine of Chinese people
      and to identify the risk factors associated with osteoporosis. BMD of the lumbar
      spine was measured by dual-photon absorptiometry in 404 healthy volunteers (266
      women and 138 men, aged 15 to 83 years) living in Lin-Kou Township. The age
      specific mean values of lumbar spine BMD were higher for men than for women after
      age 60. Furthermore, the BMD of women declined significantly after age 40.
      However, the BMD of men did not show a downward trend with age. In a multiple
      logistic regression analysis of fracture risk expressed as a categorical level of
      BMD, age, diabetes, and years since menopause were associated with lower BMD,
      while body mass index was associated with higher BMD. In a multiple linear
      regression analysis of BMD, significant variables were years since menopause,
      age, body mass index, and seaweed diet. Variables that were significant in
      bivariate analysis, but not multiple variable analysis were education, milk
      consumption, breast-feeding, frequency of pregnancy, and age at first
      menstruation. However, cigarette habits, alcohol consumption, and physical
      activity were not associated with the BMD level in any of these analyses.

PMID- 8275200
TI  - Ongoing high-risk sexual behaviors in relation recreational drug use in sexual
      encounters. Analysis of 5 years of data from the Toronto Sexual Contact Study.
AB  - The current study investigated the association between the use of recreational
      drugs at the time of sexual activity and high-risk sexual behavior in a Toronto
      cohort of 249 homosexual and bisexual men over a 5-year period commencing in 1984
      to 1985 and concluding in 1989 to 1990. The main analysis was based on a total of
      2536 visits. Univariate and multivariate Liang-Zeger regression models were used
      to relate the log of the sexual activity score (SARS) to the independent
      variables over the 20 follow-up visits while controlling for intercorrelations
      between variables from the same respondent. We found that there was a significant
      decline, over time, in the sexual activities that pose a higher risk of infection
      with human immunodeficiency virus. Recreational drugs still appear to be playing
      an important role in the continuation of higher-risk sexual activities. The use
      of poppers in conjunction with sex is a strong predictor of high-risk activity,
      as is use of alcohol and marijuana in conjunction with sex. Also, simultaneously
      strongly associated with higher-risk score is the Centers for Disease Control
      classification II. More emphasis needs to be placed on educating the population
      about the potential risks of combining reactional drugs with sexual activity.

PMID- 8275201
TI  - HIV seroprevalence in sexually transmitted disease clients in a low-prevalence
      southern state. Evidence of endemic sexual transmission.
AB  - We studied human immunodeficiency virus (HIV) seroprevalence and risk factors in
      3052 clients attending three large public, sexually transmitted disease (STD)
      clinics in central North Carolina in mid-1988. Anonymous self-administered
      questionnaires linked to HIV serologies obtained by testing extra blood from
      syphilis serologies without personal identifiers showed the following
      characteristics of the respondents: 60% were men, 81% were black, the median age
      was 24 years, 5% were injecting drug users since 1978, 7% reported a history of
      syphilis, and 8% of men were homosexual or bisexual. HIV seropositivity was found
      in 76 subjects (2.5%), including 46% of the homosexual men, 25% of the bisexual
      men, 1.6% of the heterosexual men, and 0.6% of the women. Elevated HIV
      seroprevalence rates were found in subjects with a history of or seroreactivity
      for syphilis (HIV-positive rate of 53% in homosexual or bisexual men, 9% in
      heterosexual men, 3% in women) and with histories of gonorrhea (HIV-positive rate
      of 37% in homosexual or bisexual men, 2.6% in heterosexual men, 1% in women), and
      intercourse (41% in homosexual or bisexual men, 2% in women), prostitute contact
      (5% in heterosexual men), and sex with casual partners (2% in women). Even a
      state with a low incidence of acquired immunodeficiency syndrome can include
      subpopulations with a high HIV seroprevalence, apparently disseminated
      endemically in association with bacterial STDs.

PMID- 8275202
TI  - Inferences on the potential effects of presumed nondifferential exposure
      misclassification.
AB  - In the presentation and discussion of epidemiologic study results, investigators
      often argue that their results have to be viewed as conservative due to the
      occurrence of presumedly nondifferential exposure misclassification. Sometimes
      attempts are made to correct for this supposed bias toward the null.
      Particularly, various dual exposure measurement strategies that may eliminate or
      at least reduce the bias if the exposure misclassification is truly
      nondifferential have gained much popularity in recent years. However, even in
      cohort studies, it is often questionable whether the exposure misclassification
      rates are completely independent of measured disease risk. In this article, I
      assess the effects of violating the assumption of nondifferential
      misclassification on the direction and magnitude of bias and on the
      misclassification correction procedures. Even slight violation of the
      nondifferentiality assumption can lead to large bias away from the null or to
      crossover bias, particularly if dual measurement procedures are used to correct
      for exposure misclassification. Consequently, inferences on the potential effects
      of presumedly nondifferential exposure misclassification in any given study
      should only be made after careful sensitivity analyses that take into account the
      full range of plausible misclassification rates as well as of plausible
      deviations from nondifferentiality.

PMID- 8275203
TI  - Waist-hip ratio measurement location influences associations with measures of
      glucose and lipid metabolism. The San Luis Valley Diabetes Study.
AB  - The ratio of waist to hip circumference is widely used to characterize fat
      distribution patterns but the locations for measurement are not standardized.
      Between 1986 and 1988, we measured two waist and two hip circumferences on 616
      Hispanic and non-Hispanic white subjects, aged 30 to 74 years. Intraclass
      correlation coefficients, based on repeat measurements of 38 subjects, showed
      that minimum waist and maximum hip circumferences attained or exceeded the level
      of repeatability seen with the landmark-based circumference measures. Sex
      specific partial correlation coefficients, adjusted for age and body mass index,
      indicated wide variation in the magnitudes of associations of the two waist-hip
      ratios with measures of insulin, high-density-lipoprotein cholesterol,
      triglycerides, and diastolic blood pressure. Models with simple waist
      circumference generally produced partial correlation coefficients of equal or
      greater magnitude compared to the coefficients seen with the waist-hip ratio.

PMID- 8275204
TI  - Performance of semiquantitative food frequency questionnaires in international
      comparisons. Mexico City versus San Antonio, Texas.
AB  - International dietary comparisons present a number of methodologic difficulties.
      We developed two semiquantitative food frequency questionnaires for use in Mexico
      City and San Antonio, Texas. The Mexico City questionnaire contained 85 food
      items and the San Antonio questionnaire contained 108. Thirty-six items were
      common to both questionnaires. The questionnaires were administered to 128
      Mexican Americans, 35 to 64 years old, residing in a low-income barrio
      neighborhood of San Antonio and to 644 similarly aged Mexicans residing in a low
      income "colonia" of Mexico City. Major differences in fat and carbohydrate intake
      as a percent of total kilocalories were observed between the two study groups,
      with Mexico City residents consuming approximately 18 to 21% of calories from fat
      and 68 to 72% from carbohydrate compared to 29 to 33% from fat and 48 to 52% from
      carbohydrate for Mexican Americans from San Antonio. Both of these differences
      were highly statistically significant (P < 0.001). A number of arguments support
      the validity of these findings. First, the distribution of high- and low-fat
      foods was similar on both questionnaires. Also, of the top-ten foods (as
      contributors to total kilocalorie intake) in San Antonio, seven were high in fat
      (> 30% of kilocalories), whereas this was true of only three of the top-ten foods
      in Mexico City.

PMID- 8275205
TI  - Postmenopausal unopposed estrogens. Characteristics of use in relation to the
      risk of endometrial carcinoma.
AB  - To determine whether treatment regimens for unopposed estrogens can be tailored
      so as to minimize the excess risk of endometrial cancer, results from 19
      published studies of the association between unopposed estrogen use and
      endometrial cancer were compiled. We sought to examine the influence of duration
      of use, recency, dose, type of estrogen preparation, and periodic interruption of
      use on cancer incidence. Estrogen use for 5 years or longer was examined in 18
      studies and was associated with a large increase in the risk of endometrial
      cancer in each one (range in relative risk, 1.8 to 36). Use for shorter durations
      also was observed to increase risk; however, among women who used estrogens for
      less than 6 months, any increased risk that may exist appears to be very small in
      size (six studies; range, 0.6 to 1.4). Risk consistently was seen to decrease
      with increasing time since cessation of use, although there is evidence from
      seven of eight studies that some residual excess risk remains long after
      estrogens have been discontinued. In each of 12 studies that examined the
      influence of dose, all dose levels of conjugated estrogens increased risk of
      endometrial cancer substantially. Four of five studies found no differences
      between oral synthetic estrogens and conjugated estrogens with respect to cancer
      risk, and all of eight studies found no difference between cyclic and continuous
      regimens. Based on our review, we conclude that apart from minimizing the
      duration of use, there is no way of taking unopposed postmenopausal estrogens
      that reduces their potential to cause endometrial cancer.

PMID- 8275206
TI  - The role of environmental epidemiology in public policy.

PMID- 8275207
TI  - Intercommunity variations in the association between social ties and mortality in
      the elderly. A comparative analysis of three communities.
AB  - Identical measures of social ties obtained from three community-based cohorts
      aged 65 and over from East Boston, MA; New Haven, CT; and two rural counties in
      Iowa permit the first direct cross-community comparison of the hypothesis that
      social isolation increases 5-year mortality risks (1982 to 1987) for older men
      and women. In sex-specific proportional hazards analyses, social ties were
      significantly and inversely related to mortality independently of age in all
      three cohorts (e.g., relative hazard (RH) = 1.97 to 3.06 for men and women,
      comparing those with no ties to those with four types of ties). After controlling
      for age, pack-years of smoking, body mass, chronic conditions, angina, and
      physical and cognitive disability, social ties remain significant predictors of
      mortality risk for the men and women in New Haven (RH = 2.4 and 1.8) and for
      women in Iowa (RH = 1.9). For the men in Iowa (RH = 1.4) and the men and women in
      East Boston (RH = 1.0 and 1.3), the associations are weaker and nonsignificant.

PMID- 8275208
TI  - Glucose tolerance and mortality from ischemic heart disease in an elderly
      population. Impact of repeated glucose measurements.
AB  - The impact of glucose tolerance, measured repeatedly, on the mortality from
      ischemic heart disease (IHD) was assessed in a cohort of 202 elderly patients,
      aged 64 to 84 years in 1971, from a general practice. During the period from 1971
      to 1975 the participants were examined annually. The area under the glucose
      tolerance curve (AUC) was used as a summary index, and for every subject the mean
      AUC over the 5-year period was calculated. This index was most strongly
      correlated with the mean 60-minute glucose level (r = 0.96). Between 1975 and
      1987, 125 participants died, 28.8% of whom died from IHD. No association between
      a single measurement of glucose tolerance and IHD mortality was observed.
      However, using the mean AUC over the 5-year period, a positive association was
      observed, independent of age, sex, and other potential confounders (P = 0.04).
      These results indicate that glucose tolerance independently predicts mortality
      from coronary heart disease in an elderly cohort, provided that information on
      repeated measurements is taken into account. A continuous risk gradient is
      suggested.

PMID- 8275209
TI  - Modification of the relationship between the Quetelet index and mortality by
      weight-loss history among older women.
AB  - The effect of weight on mortality was examined using data from the first National
      Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow-up Study
      for white women aged 65 to 74 years at baseline. There was a U-shaped curve
      relating the Quetelet index categories to total mortality, with increased risk
      for both lean and heavy women. However, the increased risk to lean subjects
      occurred only among those who had lost more than 8.55% from their reported
      lifetime maximum weight. Controlling for baseline medical conditions, excluding
      early years of follow-up, and limiting the analysis to never-smokers did not
      greatly change the results. Lean women with stable weight have the lowest risk of
      mortality, while those who have lost weight have a high risk. Heavy women have a
      high risk of mortality regardless of weight-loss history. Thus, the effect of
      weight on mortality is modified by history of weight loss in older women, even
      when accounting for factors associated with weight loss and increased mortality
      risk.

PMID- 8275210
TI  - Physical activity and its association with plasma lipids and lipoproteins in
      elderly women.
AB  - The association of physical activity to plasma lipid and lipoprotein levels was
      examined cross-sectionally in 634 elderly, postmenopausal women whose mean age
      was 70.7 years. Leisure-time physical activity in kilocalories per week was
      assessed by the Paffenbarger Questionnaire, a composite index of
      sports/recreation, stair climbing, and walking. Subjects were categorized by
      tertile of kilocalories per week from total physical activity, number of flights
      of stairs climbed, and number of blocks walked. After adjustment for age, body
      mass index, education, and oral estrogen use, no significant differences were
      noted in total cholesterol, high-density-lipoprotein cholesterol (HDL-C), HDL2-C,
      HDL3-C, low-density-lipoprotein cholesterol (LDL-C), or triglycerides across
      tertile of total activity or number blocks walked. Total cholesterol was
      significantly different across tertile of number of flights of stairs climbed (P
      < 0.05), and only a borderline association was noted with LDL-C (P < 0.08). The
      study suggests that leisure-time physical activity, as measured by the
      Paffenbarger Questionnaire, is not associated with a favorable lipid profile in
      elderly, postmenopausal women. Failure to find an association may reflect the
      relatively small number of women who engaged in moderate- or high-intensity
      activity.

PMID- 8275211
TI  - Recruitment of adults 65 years and older as participants in the Cardiovascular
      Health Study.
AB  - Few large-scale epidemiologic studies have enrolled older adults; hence, little
      is known about the feasibility of recruiting this group for long-term population
      based studies. In this article we present the recruitment experience of the
      Cardiovascular Health Study (CHS), a population-based, longitudinal study of
      cardiovascular diseases in adults 65 years and older. Participants were sampled
      from the Health Care Financing Administration's (HCFA) Medicare eligibility lists
      in four US communities. Letters were mailed to 11,955 sampled individuals.
      Persons recruited were required to complete an extensive home interview and then
      a 4-hour in-clinic examination. Excluded were persons who were expected to be
      able to complete the baseline examination and who were not expected to return for
      the 3-year follow-up. Some 3654 participants were recruited from those randomly
      selected from the Medicare sampling frame. In addition, 1547 other age-eligible
      persons living in the household with the sampled individuals also participated,
      yielding a total of 5201 participants. Of those who were contacted, 9.6% were
      ineligible and 34.9% refused participation. Among those eligible, 38.6% refused
      and 57.3% were enrolled (the remaining did not refuse but were not enrolled
      before the recruitment ended). Data from a subsample indicate that compared to
      those who were ineligible or who refused, enrolled participants were younger,
      more highly educated, more likely to be married, and less likely to report
      limitations in activity. Compared to those who were eligible but refused,
      enrolled participants were less likely to have high blood pressure and stroke and
      more likely to have quit smoking and to perceive their health status as very good
      or excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275212
TI  - Gender differences in health indicators by longest-held occupation and industry
      of longest employment.
AB  - As more women enter the work force, they may increasingly come into contact with
      occupational and industrial hazards. The distribution of longest-held occupation
      and industry of longest employment and selected health indicators are presented
      for US men and women. These data are based on the National Center for Health
      Statistics' 1980 National Health Interview Survey, the first survey to collect
      data on longest-held, in addition to current, occupation and industry of
      employment. Data on limitation of activity, disability days, and physician and
      dentist visits are presented by categories of longest-held occupation and
      industry of longest employment. Overall, more men than women (except for younger
      female farm laborers and farm foremen) reported a limitation of activity due to
      chronic conditions; however, more women reported days of restricted activity.
      Female private household workers reported over a month of restricted activity.
      This study suggests the need to further investigate more direct health measures
      of female farm and agriculture workers and female private household workers.

PMID- 8275213
TI  - Coffee, tea, and mortality.
AB  - Except for conflicting evidence about coffee and risk of coronary disease, coffee
      and tea are not linked to major causes of death. Because of widespread use of
      both beverages and limitations of prior studies, concern persists. Using Cox
      models (ten covariates) we studied relations in 128,934 persons to 4501
      subsequent deaths. Except for slightly increased risk from acute myocardial
      infarction among heavier (> or = 4 cups/d) coffee users (relative risk versus
      nondrinkers = 1.4, 95% confidence interval = 1.0 to 1.9, P = 0.07), there was no
      increased risk of mortality for all deaths (relative risk per cup of coffee per
      day = 0.99, 95% confidence interval = 0.97 to 1.01; relative risk per cup of tea
      per day = 0.98, 95% confidence interval = 0.96 to 1.00) or major causes in
      adjusted analyses. Coffee was related to lower risk of liver cirrhosis death
      (relative risk per cup of coffee per day = 0.77, 95% confidence interval = 0.67
      to 0.89). Use of both beverages was related to a lower risk of suicide,
      progressively lower at higher coffee intake (relative risk per cup of coffee per
      day = 0.87, 95% confidence interval = 0.77 to 0.98). We conclude that coffee and
      tea have no overall relation to mortality risk. If coffee increases coronary
      risk, this is balanced by an unexplained lower risk of other conditions, notably
      cirrhosis and suicide.

PMID- 8275214
TI  - Gender and age differentials in risk factors for childhood malnutrition in
      Bangladesh.
AB  - A case-control study of risk factors of clinical marasmus was undertaken to
      determine which factors differed according to gender and age groups. Case
      patients were children whose mid-upper arm circumference measured less than 110
      mm and control subjects were children matched for age and sex with an arm
      circumference more than 120 mm. Between June 1988 and June 1989, 164 such pairs
      of children aged 1 to 4 years were studied. The effect of various demographic,
      socioeconomic, environmental, and health factors was investigated in a
      multivariate analysis using conditional logistic regression. Results showed an
      increased risk of marasmus among children with siblings under 5 years old. This
      increased risk was observed irrespective of gender or age. Children who consumed
      formula foods also had an increased risk of marasmus. Again, this elevated risk
      was maintained for boys and girls. Overall, higher maternal education was
      associated with a reduced risk of marasmus; however, this was only statistically
      significant for boys and for children 18 months or older. Religion was also
      associated with marasmus but only in older children (> or = 18 months). These
      results indicate that better strategic planning is necessary to formulate
      effective interventions to reduce severe malnutrition, particularly in societies
      where strong age- and sex-preferential behavior exists.

PMID- 8275215
TI  - Breast-feeding and maternal smoking in the etiology of Crohn's disease and
      ulcerative colitis in childhood.
AB  - Medical records concerning pediatric or adolescent patients first diagnosed with
      Crohn's disease or ulcerative colitis in two New York hospitals during a 5-year
      period (1986 to 1990) were abstracted, and information concerning sex, age, race,
      birthplace, sibship size, birth order, maternal age at birth, month of birth,
      duration of breast-feeding, and maternal smoking was recorded. Medical records of
      patients presenting at the respective pediatric gastroenterology departments
      immediately before or after the patients with inflammatory bowel disease were
      seen were also abstracted in order to generate a control series. Data concerning
      68 patients with Crohn's disease, 39 patients with ulcerative colitis, and 202
      control patients were analyzed through multiple logistic regression. Breast
      feeding was negatively associated with Crohn's disease (P approximately 0.04) and
      ulcerative colitis (P approximately 0.07), with relative risk point estimates
      around 0.5 and with evidence of duration-dependent trends in both instances.
      There was no evidence of association of either disease with maternal age at
      birth, birth order, maternal smoking, or season of birth.

PMID- 8275216
TI  - Dietary intervention study in children (DISC) with elevated low-density
      lipoprotein cholesterol. Design and baseline characteristics. DISC Collaborative
      Research Group.
AB  - The Dietary Intervention Study in Children (DISC) is a multicenter prospective
      study designed to assess the efficacy and safety of a lipid-lowering diet in 8-
      to 10-year-old children with moderately elevated low-density-lipoprotein
      cholesterol (LDL-C) levels. Six-hundred sixty-three children were randomized to a
      dietary intervention group (n = 334) and a usual-care group (n = 329). At
      baseline, mean LDL-C levels, nutrient intakes, anthropometric measures, and blood
      pressures were similar in the two groups. The intervention consists of a series
      of group and individual sessions to teach children and their families to follow a
      diet containing 28% of calories as total fat (< 8% as saturated fat, up to 9% as
      polyunsaturated fat, 11% as monounsaturated fat) and dietary cholesterol intake
      less than 75 mg/1000 kcal (< 150 mg/d) and designed to meet nutritional
      requirements of growing children. The usual-care group was provided with a packet
      of general dietary information only. Efficacy of the intervention will be
      assessed by comparing changes in LDL-C levels between the two groups at 36
      months. Primary safety outcome assessments will involve comparisons of linear
      growth and serum ferritin levels. Secondary safety outcomes include serum zinc,
      folate, retinol, and albumin levels; ratio of LDL-C to high-density-lipoprotein
      cholesterol; sexual maturation; cognitive development; and child behavior. Thus,
      DISC aims to address long-term efficacy and concerns about the overall safety of
      dietary modifications in growing children.

PMID- 8275217
TI  - Subarachnoid hemorrhage, cerebral hemorrhage, and serum cholesterol concentration
      in men and women.
AB  - The role of serum cholesterol in predicting the risk of stroke is unclear and may
      depend on the subtype of the disease. In 1964 to 1965, 54,385 Swedish men and
      women participated in a health survey with serum cholesterol and diastolic blood
      pressure determinations. The Swedish mortality register was used to identify
      causes of death in this cohort during 20.5 years of follow-up (1964 to 1985). A
      person-year-based Poisson model was used for multivariate analysis. Relative risk
      increased with decreasing serum cholesterol level for subarachnoid hemorrhage in
      men and for cerebral hemorrhage in women but not for subarachnoid hemorrhage in
      women. For cerebral hemorrhage in men, the risk function was U-shaped. Adjustment
      for diastolic blood pressure did not significantly change the relation between
      the risk for any of the different stroke types and the cholesterol level. A low
      cholesterol level predicts death from intracranial bleeding, but the data suggest
      that there is differing risk pattern for men and women.

PMID- 8275218
TI  - Five-year changes in population blood pressure and hypertension prevalence.
      Results from the MONICA Augsburg surveys 1984/85 and 1989/90.
AB  - Two cardiovascular risk factor surveys were carried out in 1984/85 and 1989/90 in
      the Augsburg study region of the international World Health Organization (WHO)
      Monitoring Trends and Determinants of Cardiovascular Disease (MONICA) project.
      Independent random samples of the 25- to 64-year-old population were examined at
      each survey. Five-year changes in blood pressure (BP) and hypertension parameters
      were monitored in a population not targeted by any formal intervention program.
      Response rates in both surveys ranged close to 80%. Evaluation of selected
      quality indicators confirmed comparability of the two surveys in terms of BP
      measurement quality. Small but consistent decreases in mean systolic and
      diastolic BP were observed, particularly for women 35 years and older, whereas BP
      changes in men were less pronounced and inconsistent. Likewise, downward shifts
      of the 10th, 50th, and 90th percentiles of systolic and diastolic BP occurred in
      women and their slopes of BP rise with age decreased while such changes were less
      clear in men. The age-standardized prevalence of men and women with hypertensive
      BP (HBP; > or = 160/95 mm Hg) decreased slightly. This contrasted with rises in
      the prevalence of actual hypertension (those with HBP plus those taking
      antihypertensive drugs) for 45- to 64-year-old men, which originated from changes
      in hypertension management involving a more frequent drug treatment of borderline
      hypertensive men (140 to 159/90 to 94 mm Hg) in 1989/90. There were notable
      overall increases in the awareness, treatment, and control of men and women with
      hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275219
TI  - The health risks of smoking. The Framingham Study: 34 years of follow-up.
AB  - This study summarizes the effects of both the rate and the cumulative dose of
      cigarette smoking on the health of the original Framingham cohort, 5209
      individuals aged 30 to 62 years at entry. After 34 years of follow-up, it was
      observed that cigarette smoking was the prime determinant of chronic cough, and
      reduced both forced vital capacity and the 1-second forced expiratory volume. A
      significant relationship was observed between cigarette smoking and the incidence
      of cancer of the lung, stroke and transient ischemic attacks, intermittent
      claudication, and total cardiovascular disease, and most especially the average
      annual death rate. Cigarette smoking was significantly related to coronary heart
      disease in men 45 to 64 years old, although not related in women or older men.
      The data confirm and extend the evidence of the detrimental influence of
      cigarette smoking on health.

PMID- 8275220
TI  - Cigarette smoking, leukemia, and multiple myeloma.
AB  - To evaluate previously reported associations with cigarette smoking, the
      incidence of leukemia and multiple myeloma was determined with follow-up of up to
      24 years of 57,224 never-smokers, 20,928 former smokers, and 64,839 current
      cigarette smokers who received multiphasic health checkups. Cigarette smoking was
      associated with the development of acute nonlymphocytic leukemia in men only
      (relative risk, 2.8; 95% confidence interval, 1.2 to 6.4). Chronic myeloid
      leukemia showed an association with smoking of borderline significance in men
      only. Chronic lymphocytic leukemia and multiple myeloma were not related to
      cigarette smoking. In the men with acute nonlymphocytic leukemia there was a
      suggestion of a dose-response relation but it was not statistically significant.
      The association of cigarette smoking with acute nonlymphocytic leukemia was not
      explained by alcohol or coffee consumption or exposure to occupational hazards.
      This study adds to the growing body of evidence that cigarette smoking
      predisposes to acute nonlymphocytic leukemia in men.

PMID- 8275221
TI  - The association of bladder cancer risk with ethnicity, gender, and smoking.
AB  - This study examined patterns of invasive bladder cancer by ethnicity and gender.
      Odds ratios were computed by comparing 593 patients of known smoking status and
      diagnosed during the period from 1984 to 1988 with a randomly selected referent
      group using a logistic regression model that adjusted for differences in age and
      current occupation. Age-adjusted incidence rates for non-Hispanic whites were
      approximately twice those of Hispanics and Asian and Pacific Islanders. After
      adjustment for smoking and occupational exposures, the risks did not differ
      significantly, indicating that ethnic differences in bladder cancer incidence may
      be related to smoking and occupational exposures. The odds ratio for males
      relative to females was 5.95 (95% confidence interval (CI), 4.36 to 8.12), after
      adjustment for ethnicity, smoking status, occupation, and age, suggesting that
      gender differences not previously identified may play an important role in the
      etiology of bladder cancer. Odds ratios associated with amount smoked per day,
      for current smokers relative to nonsmokers, ranged from 1.04 for those smoking
      less than 1 pack per day (95% CI, 0.62 to 1.71) to 6.84 for those smoking 2 or
      more packs per day (95% CI, 4.67 to 10.03).

PMID- 8275222
TI  - A comparison of risk factors for human immunodeficiency virus and hepatitis B
      virus infections in homosexual men.
AB  - We analyzed cross-sectional data from 1062 homosexual men recruited in Baltimore
      during 1984, to directly compare risk factors for human immunodeficiency virus
      (HIV) and hepatitis B virus (HBV). Using polychotomous logistic regression, risk
      factor odds ratios (ORs) and 95% confidence intervals were determined for men
      with HIV alone, men with HBV alone, and men with both HIV and HBV, compared to
      seronegative men, and paired comparisons among these subgroups. Factors
      associated with the serologic prevalence of HIV alone and HBV alone (with
      respective ORs) included and receptive intercourse (HIV OR = 1.23; HBV OR =
      1.12), history of gonorrhea (HIV OR = 4.58; HBV OR = 2.52), and rectal douching
      (HIV OR = 1.41; HBV OR = 1.20). Additional factors associated with HBV alone were
      years of homosexual activity (OR = 1.65), sexual activity with a person who
      developed acquired immunodeficiency syndrome (AIDS) (OR = 1.98), and lifetime
      number of male sex partners (OR = 1.25). HIV and HBV coprevalence was associated
      with anal receptive intercourse (OR = 1.36), history of gonorrhea (OR = 2.94),
      rectal douching (OR = 1.45), sexual activity with a person who developed AIDS (OR
      = 3.87), lifetime number of male sex partners (OR = 1.21), and the lifetime sum
      of sexually transmitted diseases (OR = 1.47). These findings reinforce the need
      for following safer-sex guidelines to prevent both infections and in the case of
      HBV, the prevention strategies should include vaccination.

PMID- 8275223
TI  - Validity of physicians' self-reports of cardiovascular disease risk factors.
AB  - To determine the accuracy of self-reported risk factors in 78 physicians, self
      reported information was compared to findings on a standardized examination.
      Measured weight (r = 0.98), height (r = 0.95), body mass index (r = 0.96),
      systolic blood pressure (SBP) (r = 0.72), and diastolic blood pressure (DBP) (r =
      0.60) were highly correlated with self-reported values (all P < 0.0001). Mean
      self-reported SBP and DBP did not differ from measured values; measured weight
      was 1.5 kg greater and measured height 1.4 cm less than self-reported values
      (both p < 0.0001). Regression of measured on self-reported values indicated
      excellent agreement except for DBP and heart rate. Differences between measured
      and self-reported values were not associated with a variety of variables except
      for a greater difference in SBP at higher levels of SBP. None of the 60 self
      reported nonsmokers had expired carbon monoxide levels greater than 10 ppm. These
      results indicate that physicians' self-reports of height, body mass index, SBP,
      and smoking are extremely accurate and suitable for research purposes.

PMID- 8275224
TI  - Epidemiology of aging comes of age.

PMID- 8275225
TI  - Rising trends in melanoma--an hypothesis concerning sunscreen effectiveness. The
      Photobiology Committee of the Skin Cancer Foundation.

PMID- 8275226
TI  - Failure to induce long-term depression by an anti-correlation procedure in area
      CA1 of the rat hippocampal slice.
AB  - We have independently in our two laboratories re-examined the report by Stanton
      and Sejnowski (Nature, 339, 215-218, 1989) that single stimuli to a test pathway
      in area CA1 of the hippocampal slice, when delivered between short bursts of
      stimuli to a second, convergent pathway, produce an associative long-term
      depression (LTD) in the test pathway. While robust associative LTP was observed
      when stimuli to the two inputs were correlated in time, the anti-correlation
      procedure failed to induce LTD; rather, a trend towards potentiation was
      observed. This result was obtained using both submerged and interface chambers,
      and in two different strains of rat. A transient depression lasting for a few
      minutes could usually be elicited by strong tetanic stimulation; this depression
      was not restricted to activated pathways.

PMID- 8275227
TI  - In vitro and in vivo analysis of a rat bipotential O-2A progenitor cell line
      containing the temperature-sensitive mutant gene of the SV40 large T antigen.
AB  - Primary cultures from neonatal optic nerve contain pluripotential O-2A progenitor
      cells that are capable of differentiating into oligodendrocytes, type-2
      astrocytes or adult O-2A progenitors (O-2Aadult). Since primary optic nerve
      cultures contain a mixture of glial cell types of which only a small number are O
      2A progenitors, experiments on cell lineage and differentiation carried out using
      these cultures are both intrinsically limited and difficult to interpret.
      Ideally, cells from a clonal cell population would provide the optimal starting
      material for biological studies. In this paper we describe the creation of an O
      2A progenitor cell line using a retrovirus carrying a temperature-sensitive
      mutant SV40 large T antigen gene. This cell line has provided sufficient numbers
      of cells to allow analysis of their in vitro properties and their behaviour
      following transplantation into an in vivo environment. At the non-permissive
      temperature (39 degrees C), these cells differentiate into oligodendrocytes and
      type-2 astrocytes in a similar fashion to O-2A progenitor cells from primary
      cultures (O-2Aprim). When grown in media containing platelet-derived growth
      factor and basic fibroblast growth factor, the cell numbers can be expanded in
      culture without differentiating, consistent with the behaviour of O-2Aprim
      progenitor cells. By exploiting this property, it has been possible to culture
      large numbers of O-2A progenitors for in vivo analysis. In this study we have
      shown that transplantation of this O-2A cell line into glia-free areas in adult
      rat spinal cord results in differentiation of a proportion of cells into
      oligodendrocytes which are capable of myelinating axons. Furthermore,
      differentiation of O-2A cells into astrocytes was also observed, indicating that
      the bipotentiality of these cells in vitro can also be demonstrated in vivo.

PMID- 8275228
TI  - Role of voltage-gated Ca2+ channels and intracellular Ca2+ in rat sympathetic
      neuron survival and function promoted by high K+ and cyclic AMP in the presence
      or absence of NGF.
AB  - We have examined how NGF-dependent rat sympathetic neurons maintain Ca2+
      homeostasis when challenged with high K+ or 8-(4-chlorophenylthio)cyclic AMP
      (CPTcAMP), two survival factors. In the presence of NGF, high K+ (55 mM) caused a
      stable, 65% reduction in the density of cell soma voltage-sensitive Ca2+ channels
      within 2 days. Although resting [Ca2+]i was elevated by 1.6-fold, this was 50%
      less than the rise in [Ca2+]i measured before down-regulation occurred,
      suggesting that down-regulation may help prevent the toxic effects of
      persistently elevated [Ca2+]i. Inhibition of protein synthesis by cycloheximide
      blocked recovery from down-regulation. Moreover, treatment with cycloheximide or
      actinomycin-D caused a 2-fold rise in the peak Ca2+ current, suggesting that
      voltage-sensitive Ca2+ channel activity may be tonically attenuated during normal
      growth. In the absence of NGF, neurons survived for several days in high K+
      medium with no significant rise in resting [Ca2+]i, although neurites did not
      grow. Neither Ca2+ channel density nor resting [Ca2+]i were altered in neurons
      surviving with CPTcAMP. Moreover, CPTcAMP lowered the dependence on extracellular
      Ca2+. However, the dihydropyridine antagonist nitrendipine blocked both high K(+)
      and CPTcAMP-dependent survival although it had no effect in the presence of NGF.
      Thus, in the absence of NGF, sympathetic neurons do not require elevation of
      [Ca2+]i above resting levels to survive with either high K+ or CPTcAMP, but
      dihydropyridine-sensitive Ca2+ channel activity may be essential for their
      survival promoting actions.

PMID- 8275229
TI  - Taurine release evoked by NMDA receptor activation is largely dependent on
      calcium mobilization from intracellular stores.
AB  - It is known that the activation of N-methyl-D-aspartate (NMDA) receptors leads to
      an increase in extracellular taurine concentration in different brain regions.
      The mechanism that mediates this effect is not totally understood. In this study,
      rat hippocampal slices were used to determine the dependence of NMDA-induced
      taurine release on extracellular calcium and/or on calcium mobilization from
      intracellular stores. NMDA was administered through a microdialysis probe
      inserted into the slice, at the level of CA1 stratum radiatum, which was also
      used to collect amino acids from the extracellular space. Field potentials evoked
      by stimulation of the Schaffer collaterals and recorded in the stratum pyramidale
      of CA1 were used as a control of NMDA receptor activation. NMDA induced a marked
      increase in extracellular taurine levels and a decrease in field potential
      amplitude, and both effects were suppressed in the presence of MK-801, a blocker
      of the NMDA receptor-linked channel. Dantrolene, an inhibitor of calcium release
      from intracellular stores, partially inhibited the extracellular taurine
      increase, while 2-nitro-4-carboxyphenyl-N,N-diphenyl carbamate (NCDC), an
      inhibitor of phosphatidylinositol-specific phospholipase C activation, had no
      effect. Removal of extracellular calcium diminished, but did not abolish, the
      extracellular taurine increase caused by NMDA. The remaining taurine response was
      totally suppressed by dantrolene, and also by NCDC. These results demonstrate
      that the release of taurine induced by NMDA receptor activation is triggered by
      the increase in cytoplasmic calcium concentration. We suggest that, under
      physiological conditions, calcium influx provides the signal for NMDA-induced
      taurine release, which is amplified by calcium-dependent calcium mobilization
      from intracellular stores.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275230
TI  - Methoxyverapamil reduction of nicotine-induced catecholamine release involves
      inhibition of nicotinic acetylcholine receptor currents.
AB  - The mechanism by which the putative Ca2+ channel blocker methoxyverapamil (D600)
      inhibits nicotine-induced catecholamine release was investigated in bovine
      adrenal chromaffin cells and in neurons from paravertebral sympathetic ganglia of
      chick embryos. We found D600 to prevent catecholamine release evoked by 30 s
      applications of nicotine with a significantly higher potency than the release
      induced either by 30 s K+ depolarizations or by electrical field stimulation of
      sympathetic neurons. Like the use-dependent action of D600 upon Ca2+ channels,
      the magnitude of inhibition of the K(+)-evoked secretion depended on the duration
      of stimulation (10 s to 5 min). Data on catecholamine release were supplemented
      by patch-clamp recordings. We found whole-cell currents in chromaffin cells
      evoked by (extrapolated) 0.5 s applications of nicotine to be significantly more
      sensitive to D600 than Ca2+ currents induced by a 0.5 s depolarization from -80
      to 0 mV. In both instances, the potency of D600 depended on the duration of the
      (nicotinic and depolarizing) stimuli. Our data suggest that D600 inhibits
      nicotine-induced catecholamine release by reducing nicotinic acetylcholine
      receptor currents rather than voltage-gated Ca2+ currents. Hence, in chromaffin
      cells as well as in sympathetic neuronal preparations, D600 does not appear to be
      a suitable tool to investigate the part voltage-activated Ca2+ currents play in
      cellular events induced by nicotine.

PMID- 8275231
TI  - Adenoviral vector as a gene delivery system into cultured rat neuronal and glial
      cells.
AB  - Previous studies have demonstrated that a defective recombinant adenovirus can
      infect a wide range of postmitotic and slowly proliferating cell types such as
      hepatocytes, myotubes, pneumocytes and intestinal cells (Stratford-Perricaudet et
      al., Hum. Gene Ther., 1, 241-256, 1990; Quantin et al., Proc. Natl. Acad. Sci.
      USA, 89, 2581-2584, 1992; Jaffe et al., Nature Genetics, 1, 372-378, 1992). We
      have used a defective recombinant adenovirus, Ad.RSV beta gal, containing the
      Escherichia coli beta-galactosidase gene targeted to the nucleus under the
      transcriptional control of the Rous sarcoma virus long terminal repeat promoter
      (Stratford-Perricaudet et al., J. Clin. Invest., 90, 626-630, 1992) to infect non
      dividing neural cells in primary culture. We show that 80-100% of neuronal and
      astroglial cells infected with a viral titre lower than 10(9) p.f.u./ml express
      beta-galactosidase for at least 1 month without cell damage. These results
      demonstrate the potential usefulness of recombinant adenovirus infection for the
      analysis of brain-specific gene regulation and for the transfer of genes into
      neural cells before their transplantation into the brain.

PMID- 8275232
TI  - Ribosome-inactivating proteins from plants as agents for suicide transport and
      immunolesioning in the nervous system.

PMID- 8275233
TI  - Distribution and characterization of neuropeptide FF-like immunoreactivity in the
      rat nervous system with a monoclonal antibody.
AB  - Monoclonal antibodies against neuropeptide FF were produced and characterized.
      The antibodies are directed and highly specific to neuropeptide FF, and
      reactivity requires the C-terminal dipeptide of neuropeptide FF (Arg-Phe-NH2).
      Tissue extracts from bovine spinal cord, rat spinal cord and hypothalamus were
      analysed by high-pressure liquid chromatography coupled with radioimmunoassay
      using the characterized monoclonal antibody. Only one immunoreactive peptide was
      detected and it coeluted with authentic neuropeptide FF. Using this highly
      specific monoclonal antibody, the distribution of neuropeptide FF-like
      immunoreactivity was further studied by indirect immunohistochemistry.
      Immunoreactivity was seen in two major cell groups in the rat brain. The largest
      cell group was located in the medial hypothalamus between the dorsomedial and
      ventromedial nuclei. The other one was found in the nucleus of the solitary
      tract. Fibres immunoreactive for neuropeptide FF were located in the lateral
      septal nucleus, amygdala, different hypothalamic areas, nucleus of the solitary
      tract, ventral medulla, trigeminal complex and the dorsal horn of the spinal
      cord. Spinal and sympathetic ganglia were non-reactive. No neuropeptide FF
      immunoreactivity was seen in the gut autonomic nervous system or endocrine cells.
      The results show that neuropeptide FF-like immunoreactivity has a clearly more
      limited distribution in the nervous system than typical brain-gut peptides.

PMID- 8275234
TI  - The contribution of intracortical connections to horizontal spread of activity in
      the neocortex as revealed by voltage sensitive dyes and a fast optical recording
      method.
AB  - Coronal slices from guinea-pig visual neocortex were stained with voltage
      sensitive fluorescence dyes RH414 or RH795. Activity was evoked by electrical
      stimulation of either the white matter or layer I. Emitted light intensity
      changes representing summated changes of membrane potential were recorded by a 10
      x 10 photodiode array with a temporal resolution of 0.4 ms and a spatial
      resolution of 94 microns. The distribution and spread of activity in the
      horizontal direction was analysed. Following stimulation of the white matter or
      layer I, two regions of activity were differentiated in the medio-lateral
      direction: a central region (approximately 1 mm wide) of high-amplitude activity
      close to the stimulation electrode and, distant from the stimulation electrode,
      peripheral regions of low-amplitude activity. Central and peripheral regions
      differed in their rates of decline, their relative extent with stimulation of
      different sites and within different layers. The total extent of non-synaptic
      evoked activity did not exceed that of the central region of high-amplitude
      activity. Along the extent of non-synaptic activity, onset latencies of
      potentials were almost constant. Thus, activity of high amplitude in the central
      region was likely mediated by simultaneous activation of distributed afferent
      fibres. In contrast, no non-synaptic activity was found in peripheral regions.
      Therefore it is suggested that this low-amplitude activity was mediated without
      direct afferent activation but via long-distance intracortical horizontal
      pathways. These pathways are known to terminate in layer III, and accordingly
      latencies of responses in the periphery were shortest in upper cortical layers,
      whereas in the central region, latencies increased from lower to upper cortical
      layers.

PMID- 8275235
TI  - A study of the barium-sensitive and -insensitive components of the action of
      thyrotropin-releasing hormone on lumbar motoneurons of the rat isolated spinal
      cord.
AB  - The electrophysiological action of thyrotropin-releasing hormone (TRH) on rat
      spinal motoneurons was studied in vitro using single-electrode voltage- and
      current-clamp techniques. In current-clamp conditions TRH elicited a slowly
      developing depolarization, associated with a large input resistance increase and
      sustained neuronal firing; the primary metabolites of TRH were ineffective. Under
      voltage-clamp conditions in the presence of tetrodotoxin, TRH evoked a large
      inward current (ITRH; peaking at approximately -40 mV) associated with a large
      input conductance fall. Only 44% of cells displayed ITRH reversal; when the chord
      conductance values of these cells were plotted against membrane potential, a bell
      shaped relation occurred, indicating voltage-dependent block by TRH of a
      persistent conductance active over a wide range of membrane potentials. ITRH
      reversal values were shifted to more positive levels in high K+ solution in
      Nernstian fashion; hence a large proportion of the TRH response is suggested to
      be mediated by the block of a K+ conductance (IK(T)). IK(T) (and its voltage
      dependent block by TRH) was resistant to certain K+ channel antagonists
      (tetraethylammonium, Cs+, 4-aminopyridine or apamin), but was depressed by Ba2+.
      The Ba(2+)-resistant fraction of ITRH was attenuated by Cd2+, Mn2+ or Co2+,
      indicating that it probably involved a Ca(2+)-sensitive inward current.
      Concomitant application of Ba2+ and Cd2+ induced a near-total block of the
      response to TRH. It is suggested that suppression of IK(T), associated with the
      onset of a Ca(2+)-sensitive current, can explain the excitatory effect of TRH on
      rat spinal motoneurons.

PMID- 8275236
TI  - Heterogeneity of metabotropic glutamate receptors in the striatum:
      electrophysiological evidence.
AB  - In order to investigate the functional role of metabotropic glutamate receptors
      (mGluRs) in the striatum we performed extracellular and intracellular recordings
      from a corticostriatal brain slice preparation. The effects of L-2-amino-3
      phosphopropionic acid (L-AP3), an antagonist of mGluRs, were studied both on long
      term synaptic depression (LTD) and on presynaptic inhibition of excitatory
      postsynaptic potentials (EPSPs) induced by different agonists of mGluRs. L-AP3
      produced a dose-dependent (3-30 microM) reduction of the LTD evoked in the
      striatum by the tetanic stimulation of the corticostriatal pathway. In contrast
      to this action, L-AP3 (10-100 microM) did not significantly affect the
      presynaptic inhibitory effect of 1-amino-cyclopentyl-trans-dicarboxylic acid (t
      ACPD), an agonist of mGluRs, on corticostriatal transmission. Higher
      concentrations of L-AP3 (0.3-1 mM) reduced by themselves the EPSP amplitude. The
      inhibitory effect of t-ACPD on the cortically evoked EPSPs was mimicked either by
      the active stereoisomer 1S,3R-ACPD or by amino-4-phosphonobutyric acid (L-AP4), a
      glutamate autoreceptor agonist. In some neurons, these inhibitory actions were
      coupled with membrane depolarizations. The depression of synaptic transmission
      caused by t-ACPD, 1S,3R-ACPD and L-AP4 was not altered following the induction of
      LTD. Chronic lithium treatment of the animals (60-120 mg/kg i.p. for 10 days)
      blocked striatal LTD but not presynaptic inhibition mediated by mGluR agonists.
      The present findings show that the mechanisms underlying LTD and the presynaptic
      inhibition induced by different agonists of mGluRs exhibit functional and
      pharmacological differences. These data suggest heterogeneity of mGluRs in the
      striatum.

PMID- 8275237
TI  - Excitatory drive from deep cerebellar neurons to the superior colliculus in the
      rat: an electrophysiological mapping study.
AB  - The cerebello-tectal projection arising from the interpositus nucleus was
      investigated electrophysiologically to test the hypothesis that the deep
      cerebellar nuclei constitute a source of tonic excitation in the superior
      colliculus. A total of 117 spontaneously active collicular neurons were recorded
      during GABA microinjection into 26 interpositus sites, where tonic single-cell
      deep cerebellar activity was also simultaneously recorded. GABA injection always
      led to suppression of interpositus activity, while in the colliculus a clear
      pattern of results emerged. 58% of superior colliculus cells showed no response
      to suppression of interpositus activity, 35% showed a frequency decrease and 7%
      showed a frequency increase. The majority of these responsive cells were found in
      a laterally located sheet of cells mainly restricted to the intermediate white
      layer, in close register with the known cells of origin of the predorsal bundle
      and completely overlapping the terminals of the nigrotectal pathway originating
      in dorsolateral substantia nigra pars reticulata. The implications of these
      results for cooperative theories of head movement control involving the superior
      colliculus, cerebellum and precerebellar nuclei are discussed.

PMID- 8275238
TI  - Covariations between hippocampal mossy fibres and working and reference memory in
      spatial and non-spatial radial maze tasks in mice.
AB  - Male mice from nine inbred mouse strains were tested at the age of 3 months in
      either a spatial or a non-spatial version of the radial maze. Only four out of
      eight arms contained food rewards, permitting simultaneous assessment of working
      and reference memory in both situations. Other animals from the same strains were
      processed histologically to estimate the strain-specific extents of the mossy
      fibre projections. No significant between-task correlations were obtained for
      either working or reference memory. However, measures of working and reference
      memory correlated with each other within tasks. This suggests that these concepts
      may perhaps not be validly used in the mouse. Large, positive correlations of the
      size of the intra- and infrapyramidal mossy fibre projection with both working
      and reference memory were obtained in the spatial radial maze task, but not in
      the non-spatial one. We conclude that heritable variations of the hippocampal
      intra- and infrapyramidal mossy fibre projection influence processes related to
      spatial learning capabilities in radial mazes.

PMID- 8275239
TI  - Introduction to special issue on vestibular control of posture and gait.

PMID- 8275240
TI  - Spatial stability, voluntary action and causal attribution during self
      locomotion.
AB  - Adaptive changes in locomotory control and perception occur in environments where
      the normal relationship between effort and body displacement is altered (1,2). We
      have further investigated this plastic relationship by altering visual feedback
      during voluntary walking in place on a rotary treadmill. When the velocity of
      optical flow was increased or reversed relative to normal for the steps being
      made, subjects reported changes in perceived self-motion, the size, rate, and/or
      direction of their voluntary steps, the extent of voluntary effort required, and
      the apparent stability of a hand-held support bar. The floor and the visual
      environment were perceived as stable. We will show that these perceptual
      remappings obey "terrestrial constraints."

PMID- 8275242
TI  - Vestibular falls.
AB  - Vestibular dysfunction is a significant differential diagnosis in patients who
      have unexpected falls without: loss of consciousness, paresis, sensory loss, or
      cerebellar deficit. Either peripheral or central vestibular disorders cause
      postural instability with preferred directions of falling, some of which can be
      attributed to either the particular plane of the affected semicircular canal or a
      central pathway mediating the 3-dimensional vestibulo-ocular reflex in yaw,
      pitch, and roll. Ipsiversive falls occur in vestibular neuritis or in
      Wallenberg's syndrome--where they are known as lateropulsion. Contraversive falls
      are typical for the otolith Tullio phenomenon, vestibular epilepsy, and thalamic
      astasia. Predominant fore-aft instability is observed in bilateral
      vestibulopathy, benign paroxysmal positioning vertigo, as well as in downbeat or
      upbeat nystagmus syndrome. Falls can be diagonally forward (or backward) and
      toward or away from the side of the lesion, depending on the site of the lesion
      (the ocular tilt reaction is ipsiversive in medullary lesions, but contraversive
      in mesencephalic lesions) and on whether vestibular structures are excited or
      inhibited.

PMID- 8275241
TI  - Influence of expectation and arousal on center-of-pressure responses to transient
      postural perturbations.
AB  - Central modulation of postural responses to external perturbations appears to be
      a function of subject expectation, which in turn depends on: 1) prior experience
      within the testing paradigm, and 2) available information specific to the
      impending perturbation. Conceivably, the effects of expectation could be
      mediated, in part, through arousal-related mechanisms. This study investigated
      the influence of expectation of "postural threat" on center-of-pressure responses
      to transient translational platform perturbations in 23 healthy young males. The
      influence of prior experience was assessed first by performing a series of
      repeated trials using moderately large perturbations. The effect of providing
      specific prior information was then evaluated by administering small "low-threat"
      and large "high-threat" perturbations, with and without prior precued information
      about the perturbation magnitude. Also assessed were the associations between the
      postural responses and changes in arousal, the latter indicated by heart rate and
      skin conductance measures. The results showed that prior testing experience had a
      profound influence on postural strategy selection and execution, whereas the
      influence of precued prior information was rather more subtle. A tendency to lean
      forward prior to perturbation was influenced both by experience and prior
      information. Marked decreases in arousal occurred over the course of the earliest
      trials, and there was also some evidence that prior information affected arousal.
      Although causal relationships cannot be established, the results did show
      evidence of association between arousal and postural responses, suggesting that
      arousal could have affected postural strategy selection and execution.

PMID- 8275243
TI  - Interaction of vestibular and proprioceptive inputs.
AB  - The study investigates the interaction of leg proprioceptive and vestibular
      afferents for human self-motion perception in space. Stimulation consisted of
      sinusoidal (0.025-0.4 Hz) and transient horizontal rotations of trunk and head in
      space (vestibular stimulus, VEST) and of the feet relative to the trunk (leg
      proprioceptive stimulus, LEG-PROP). Measures of the perception were obtained with
      the help of a pointing procedure. Leg proprioception. The perception of relative
      motion between feet and trunk during LEG-PROP was veridical across the
      frequencies tested and had a low detection threshold (0.2 degree/s). Perception
      of trunk turning in space. Trunk turning during VEST was underestimated,
      especially at low frequencies, and the threshold of the perception was > or = 1.0
      degree/s. LEG PROP evoked an illusion of trunk turning, which reached a
      considerable magnitude at low frequencies. During VEST-LEG-PROP combinations, the
      perception varied monotonously as a function of both inputs. Reflecting the
      deficiencies of its constituents, it was erroneous with 1 exception. During trunk
      rotation about the stationary feet, the perception was approximately veridical
      across frequency and its threshold was down to 0.2 degree/s, suggesting that it
      was determined essentially by leg proprioception in this condition. These
      findings resemble those previously obtained for neck proprioception and,
      therefore, were incorporated into a conceptual model of vestibular-proprioceptive
      interaction in general. In this model, first an internal notion of foot in space
      is created by summing the following high-threshold signals: head in space
      (vestibular), trunk relative to head (neck proprioceptive), and foot relative to
      trunk (leg proprioceptive). Second, further addition of low-threshold
      proprioceptive signals of trunk on foot and head on trunk yields the perception
      of trunk in space and head in space, respectively. Not included in the model is
      the finding that subjects' perceptual mode may change in certain conditions. When
      foot excursion exceeds a certain magnitude, for instance, vestibular input alone
      may determine the self-motion perception.

PMID- 8275244
TI  - Vestibular and proprioceptive modulation of postural synergies in normal
      subjects.
AB  - One way of investigating different muscle synergies underlying human balance
      control is to assume that only 1 or 2 centrally preprogrammed synergies are
      available to reestablish upright stance when it is perturbed. According to this
      hypothesis, the many, apparently different, synergies elicited by rotation or
      translation of a support-surface on which test subjects stand, in fact, result
      from a modulation of muscle responses induced by different amplitudes of afferent
      inputs. To test this hypothesis, we probed the balance control of 16 normal
      subjects with 5 combinations of rotation and translation of the support surface.
      Each combination yielded a constant angle (3 or 4 degrees) and angular velocity
      (18 and 36 degrees/s, respectively) over the first 120 ms of ankle dorsiflexion
      but resulted in differing velocities of upper leg, trunk, and head movements.
      These first 120 ms of link movements and the resulting muscle responses were
      analysed for amplitude and timing modulation using 3 techniques. First,
      velocities of initial link movements and areas of muscle EMG activity were
      examined separately for the minimum number of descriptors, which would optimally
      describe the linear variation of the interlink amplitude synergy with respect to
      the amount of support-surface rotation or translation employed to perturb
      balance. Initial trunk angular velocity, which was highly correlated with head
      linear acceleration (r = 0.9), provided the first best descriptor of initial link
      movements. Ankle angular velocity provided the second descriptor because it was
      not correlated with trunk angular velocity. The amplitude modulation synergy of
      EMG responses could be characterised by the modulation of tibialis anterior and
      paraspinal muscles between 160 and 240 ms and by that of soleus between 80 and
      120 ms after stimulus onset. The linear combination of these best descriptors of
      link movements and that for EMG response amplitudes changed continuously in an
      identical manner with changes in the stimulus combination. Second, multivariate
      linear correlations between the amplitudes of initial link velocities and muscle
      EMG response areas best describing the response amplitude synergy were examined.
      Several significant correlations (r > 0.6) were obtained between leg and trunk
      muscle activity 120 ms after stimulus onset and trunk, or upper leg angular
      velocity, or head linear velocity, prior to 120 ms. Finally, crosscorrelations
      between muscle responses were examined for consistent interlink timing synergies
      between muscle responses.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8275245
TI  - Postural consequences of long duration centrifugation.
AB  - In the present paper a series of experiments will be described in which the
      postural consequences of long (up to 1.5 h) duration 3G-centrifugation have been
      subject to investigation. A vestibular model is presented in order to explain for
      the postural imbalance found in specific conditions after the centrifuge run, and
      for the often concomitant feelings of motion sickness (50% of the subjects suffer
      from Sickness Induced by long duration Centrifugation). Finally, the possible
      relation between SIC and the Space Adaptation Syndrome is discussed.

PMID- 8275246
TI  - Vestibular bibliography.

PMID- 8275247
TI  - Visual-vestibular interaction in humans during active and passive, vertical head
      movement.
AB  - We studied visual-vestibular interaction (VVI) in 9 normal human subjects using
      active and passive vertical head rotations. Gain and phase of the vertical
      vestibulo-ocular reflex (VOR) and visually enhanced vestibulo-ocular reflex
      (VVOR) were measured for single frequency sinusoidal motion, as well as for
      sinusoidal motion of continuously increasing frequency, over the range of 0.4 to
      4.0 Hz. In addition to measurement of VVOR during normal vision, telescopic
      spectacles having a magnification of 1.9x were used to challenge VVI to
      facilitate measurement of visual enhancement of VOR gain. In the mid-frequency
      range (1.6 to 2.4 Hz), the active VOR exhibited gain closer to compensatory than
      did the passive VOR; at other frequencies, active and passive VOR gains were
      similar. VVOR gain during normal vision was compensatory for both active and
      passive motion throughout the frequency range tested. VVOR gain with 1.9x
      telescopic spectacles was greater than VOR gain at all frequencies tested,
      including up to 3.2 Hz for passive head movements, and up to 4.0 Hz for active
      head movement. However, gain enhancement with telescopic spectacles was
      consistently greater during active than during passive head movement. Phase
      errors for the VOR and VVOR were small under all testing conditions. Although
      active VOR and VVOR were directionally symmetrical, gain of upward slow phases
      differed from that of downward slow phases for passive VOR and VVOR in a manner
      depending on rotational frequency. For both active and passive testing, gain and
      phase values obtained during swept frequency rotations were similar to those
      obtained during single frequency sinusoidal testing. These data indicate that VVI
      can enhance gain of the passive vertical VOR even at frequencies above what is
      usually considered to be the upper limit of visual pursuit tracking. The
      additional enhancement observed during active head movements at these high
      frequencies is attributable to use of efference copy of the skeletal motor
      command to neck musculature.

PMID- 8275248
TI  - Loss of ipsidirectional quick phases of torsional nystagmus with a unilateral
      midbrain lesion.
AB  - We report a patient with a long-standing, unilateral lesion of the midbrain who
      showed ipsidirectional loss of torsional quick phases, impairment of all vertical
      eye movements and normal horizontal eye movements. The findings are consistent
      with recent reports of the effects of experimental lesions, in monkeys, of the
      rostral interstitial nucleus of the medial longitudinal fasciculus and the
      interstitial nucleus of Cajal.

PMID- 8275249
TI  - Three dimensional eye movements of squirrel monkeys following postrotatory tilt.
AB  - Three-dimensional squirrel monkey eye movements were recorded during and
      immediately following rotation around an earth-vertical yaw axis (160 degrees/s
      steady state, 100 degrees/s2 acceleration and deceleration). To study
      interactions between the horizontal angular vestibulo-ocular reflex (VOR) and
      head orientation, postrotatory VOR alignment was changed relative to gravity by
      tilting the head out of the horizontal plane (pitch or roll tilt between 15
      degrees and 90 degrees) immediately after cessation of motion. Results showed
      that in addition to post rotatory horizontal nystagmus, vertical nystagmus
      followed tilts to the left or right (roll), and torsional nystagmus followed
      forward or backward (pitch) tilts. When the time course and spatial orientation
      of eye velocity were considered in three dimensions, the axis of eye rotation
      always shifted toward alignment with gravity, and the postrotatory horizontal VOR
      decay was accelerated by the tilts. These phenomena may reflect a neural process
      that resolves the sensory conflict induced by this postrotatory tilt paradigm.

PMID- 8275250
TI  - A multidimensional model of the effect of gravity on the spatial orientation of
      the monkey.
AB  - A "sensory conflict" model of spatial orientation was developed. This
      mathematical model was based on concepts derived from observer theory, optimal
      observer theory, and the mathematical properties of coordinate rotations. The
      primary hypothesis is that the central nervous system of the squirrel monkey
      incorporates information about body dynamics and sensory dynamics to develop an
      internal model. The output of this central model (expected sensory afference) is
      compared to the actual sensory afference, with the difference defined as "sensory
      conflict." The sensory conflict information is, in turn, used to drive central
      estimates of angular velocity ("velocity storage"), gravity ("gravity storage"),
      and linear acceleration ("acceleration storage") toward more accurate values. The
      model successfully predicts "velocity storage" during rotation about an earth
      vertical axis. The model also successfully predicts that the time constant of the
      horizontal vestibulo-ocular reflex is reduced and that the axis of eye rotation
      shifts toward alignment with gravity following postrotatory tilt. Finally, the
      model predicts the bias, modulation, and decay components that have been observed
      during off-vertical axis rotations (OVAR).

PMID- 8275251
TI  - The vestibular system modulates masseter muscle activity.
AB  - The aim of this study was to investigate whether, and in what way, the vestibular
      input may influence the activity of the masseter muscles. The variations in the
      spontaneous electrical activity and the evoked responses in the masseter motor
      units to natural or electrical activation of the vestibular afferents were
      recorded in anesthetized guinea pigs. The effects of a unilateral lesion of the
      labyrinth on the firing rate of the masseter motor units were also studied.
      Results show that: 1) vestibular input elicited an excitatory tonic control on
      masseter muscle activity; 2) a faster labyrinthine control is driven to the
      contralateral than the homolateral masseter muscles; 3) vestibular macular input
      does exert an asymmetrical control on masseteric muscles of both sides, in
      relation to the head displacement in space. The latencies of responses recorded
      from the masseter motor units suggest that polysynaptic pathways are involved in
      connecting the vestibular system to the trigeminal complex. The possible
      anatomical substrates for this vestibulomasseteric reflex are discussed.

PMID- 8275252
TI  - Postural control reduced by subanesthetic nitrous oxide narcosis.
AB  - The effects of subanesthetic (21%) nitrous oxide (N2O) narcosis on postural
      control, as measured by posturography were studied in 12 subjects. Vibration
      induced body sway, with open and closed eyes, and body sway induced by a visual
      stimulus were evaluated. Adaptation was measured as the quotient of body sway
      variance between the second and first halves of each trial. Change in postural
      strategy was evaluated as change in the variance of shear forces relative to
      change in body sway. Subjective evaluation of narcosis was recorded. Body sway
      variance increased significantly during exposure to N2O, and equally for all body
      sway inducing stimuli. With the eyes open, adaptation to vibratory perturbation
      was significantly reduced by N2O. Postural strategy was unaffected by N2O, but
      differed significantly between stimuli, with relatively less involvement of shear
      forces during vibratory perturbation in the eyes open condition than during the
      other body sway inducing stimuli. Subjective evaluation of narcosis correlated
      with body sway variance during the visual stimulus. The present findings indicate
      that subanesthetic N2O narcosis reduces postural control. Adaptation to a balance
      disturbing stimulus, with undisturbed vision, is decreased by N2O. Visual clues
      are shown to be crucial to the postural strategy adopted to maintain balance. The
      effects of N2O are assumed to be due to impairment of sensorimotor integration in
      the CNS.

PMID- 8275254
TI  - Vestibular bibliography.

PMID- 8275253
TI  - Adaptation of the vestibulo-ocular reflex with the head in different orientations
      and positions relative to the axis of body rotation.
AB  - We investigated the influence of static head orientation and position, relative
      to the axis of body rotation, upon vestibular adaptation. With the head centered,
      displaced anterior to the axis of body rotation, or tilted 40 degrees to 45
      degrees in roll or pitch, the gain of the vestibulo-ocular reflex (VOR) was
      trained (to go either up or down) for one hour using artificial manipulation of
      the visual surround to produce a visual-vestibular mismatch. Before and after
      each training session, the VOR was measured in darkness with the head in the
      training as well as in several non-training positions. We found that transfer of
      VOR adaptation to non-training positions was almost complete when comparing head
      eccentric versus head-centered rotations. For tilts, however, transfer of VOR
      learning was far less complete suggesting that static otolith signals provide a
      strong contextual cue that gates the expression of an adaptive VOR response.
      Finally, following training to increase the VOR, gain was greater for
      centripetally than centrifugally directed slow phases. Centripetally directed
      postsaccadic drift also developed. These findings imply that the gain increase
      paradigm also leads to abnormal function of the velocity-to-position neural
      integrator, which holds eccentric positions of gaze.

PMID- 8275255
TI  - Vestibular bibliography.

PMID- 8275256
TI  - Space and the vestibular system: what has been learned?

PMID- 8275257
TI  - Evaluation of the torsional VOR in weightlessness.
AB  - The experimental concept and findings from a recent manned orbital spaceflight
      are described. Together with ongoing terrestrial and parabolic studies, the
      present experiment is intended to further our knowledge of the sensory
      integrative processing of information from the semicircular canals and the
      otolithic receptors, and to quantify the presumed otolithic adaptation to altered
      gravito-inertial force environments in a more reliable manner than to date. The
      experiment included measurement of the basic vestibulo-oculomotor response during
      active head rotation about each of the three orthogonal axes. Priority was given
      to the recording of ocular torsion, as elicited by head oscillation about the
      roll axis, and thus due to the concomitant stimulation of the semicircular canals
      and otolith receptors. Videooculography was employed for the measurement of eye
      movements; head movement was measured by three orthogonally arranged angular rate
      sensors and a triaxial linear accelerometer device. All signals were recorded
      synchronously on a video/data recorder. Preliminary results indicate alterations
      in the torsional VOR under zero-g conditions, suggesting an adaptive modification
      of the torsional VOR gain over the course of the 6-day orbital flight. In
      addition, the inflight test findings yielded discrepancies between intended and
      performed head movement, indicating impairment in sensorimotor coordination under
      prolonged microgravity conditions.

PMID- 8275258
TI  - Vestibular function and sensory interaction in space flight.
AB  - The vestibular system and vestibulo-visual interaction were examined in 11
      astronauts by the electrooculographic (EOG) method during short- and long-term
      flights on days 2, 3, 5, 9, 22, 50, 164, and 169 (experiments OPTOKINES and
      LABYRINTH). In space (flight days 2 and 3), they showed enhanced spontaneous
      vertical nystagmus, and disorders of tracking of vertical and diagonal movements
      of the stimulus which improved after active head movements. Early increasing of
      the reactivity of the cupulo-endolymphatic system (flight days 2-3) was replaced
      after 5 days of flight with a reduction of the vestibular function and an
      increase of the significance of the visual input in the formation of oculomotor
      responses to combined vestibulo-optokinetic stimulation. The type of spontaneous
      ocular reaction and vestibular stimulation of oculomotor activity under the
      conditions of weightlessness represented, on one hand, the general responses of
      sensory systems to weightlessness and, on the other hand, specificity of
      integrating and adaptive processes.

PMID- 8275259
TI  - Spatial orientation and posture during and following weightlessness: human
      experiments on Spacelab Life Sciences 1.
AB  - The 4 payload crew members of the Spacelab Life Sciences 9-day space flight in
      1991 were subjected to limited vestibular testing in flight as well as pre and
      post flight. Major differences in individual "perceptual style" appeared in their
      reaction to the visual-vestibular stimuli in the rotating dome experiment, and
      especially in the extent to which nondirectional tactile cues served to anchor
      the subjective vertical and body postural reactions. The ability of subjects to
      point to remembered target positions was degraded in space, which produced a
      tendency to point low in some subjects in flight. The eye movements and
      subjective response to sudden stops and head pitching following continuous
      spinning (dumping) were measured both in space and on the ground. Although
      subjective duration of inflight rotation for the dumping tests was shorter than
      that for the preflight tests, the postrotatory nystagmus, with or without head
      pitch, was lengthened in time constant relative to preflight. Ground tests, in
      addition to the flight experiments, investigated the changes following
      weightlessness in subjective and oculomotor reactions to whole body tilt, the
      ability to balance with eyes open and closed; leg muscles strength and stamina as
      related to posture; visual field dependence; and the perceptual and oculomotor
      reactions to horizontal linear acceleration. Several of these tests, as well as
      post-flight measures of motion sickness susceptibility, revealed subtle evidence
      of neurovestibular alterations that lasted a week or more following the 10-day
      orbital exposure.

PMID- 8275260
TI  - Vestibular endorgan of the frog after the space flight and postural alteration of
      the neurectomized frog--its morphological and functional resilience.
AB  - The vestibular organ of frogs returned from space were observed by SEM.
      Morphology of the sensory epithelia was normal, including ultrastructure, such as
      tip links and side links. The frogs' behavior and vestibular morphology after
      various types of vestibular neurectomy were studied. Vestibular neurectomy
      resulted in tilting posture toward that side. This tilting gradually decreased to
      zero and the nerve regenerated. When the same nerve was cut again after postural
      recovery, the tilting angle was smaller and recovery period was shorter than
      after the first neurectomy. When the bilateral nerves were cut and neural
      regeneration was inhibited on one side, tilting slowly developed toward that
      side. These results show that frogs' postural change is modified by both central
      compensation and peripheral vestibular function.

PMID- 8275261
TI  - Sensorimotor and perceptual function of muscle proprioception in microgravity.
AB  - Adaptive properties of the human proprioceptive systems were studied during the
      French-Soviet orbital flight (Aragatz mission, December 1988). The present space
      experiment investigated the hypothesis that the modifications of both
      biomechanical and physiological conditions occurring under microgravity involve
      considerable reorganization of body perception and postural control. The
      proprioceptive information originating in muscles is known to contribute,
      together with visual, vestibular, and sole cutaneous information to postural
      regulation. Moreover, by specifically activating the proprioceptive channel,
      muscle vibration is able to elicit both illusory movement sensations and postural
      responses. This experimental tool was used in microgravity in order to test
      various aspects of muscle sensory function. Ankle flexor and extensor vibration
      was applied under different experimental conditions. Quantitative analysis of
      motor responses was carried out on leg muscle EMG, goniometric, and kinesigraphic
      recordings. Joystick recordings and astronauts' comments were used to describe
      the kinaesthetic sensations. The main results were as follows: 1) Under
      microgravity, the sensitivity of muscle receptors remains unchanged. 2) During
      the flight, the tonic vibration reflexes (TVR) increased significantly in flexor
      muscles, which exhibited a sustained tonic activity. 3) The whole-body postural
      responses normally induced by ankle flexor muscle vibration were suppressed,
      whereas they remained unchanged or were only reduced when vibrations were applied
      to the ankle extensor muscles. In all cases, the postural response velocity
      decreased. 4) A disfacilitation of the vibration-induced postural illusions was
      observed to occur during long-term exposure to microgravity. These illusions
      became atypical however. For example: body lift illusion could be induced by
      tibialis anterior muscle vibration, whereas it was never induced in the controls.
      The characteristics of the illusory body movements described under normal gravity
      can be restored by artificially increasing the axial foot support forces during
      the flight. In conclusion, these data suggest that a functional reorganization of
      the proprioceptive information processing occurs in microgravity, affecting both
      perceptual and motor aspects of behavior. It is possible that these
      proprioceptive adaptations may be partly attributable to the new whole-body
      propulsive foot functions imposed by exposure to weightlessness and to the
      adaptation of motor behavior to the third dimension of space.

PMID- 8275262
TI  - Axial synergies under microgravity conditions.
AB  - Fast forward and backward upper trunk movements were analyzed and compared under
      microgravity and under preflight and postflight conditions. The kinematic
      analysis showed that the upper trunk movements were accompanied by hip and knee
      movements in the opposite direction both under microgravity and under normal
      gravitational conditions. This suggests that the center of mass position with
      respect to the feet is still regulated under microgravity when the feet are
      attached to the floor. The EMG analysis during backward movements shows that
      under preflight conditions a set of muscles (ErSp, BF, Sol) in the back of the
      body are activated early on. Under microgravity, the early Sol activation was
      replaced by an early TA activation, which was still present at the first
      postflight recording and was then replaced by the early Sol activation observed
      under preflight conditions. This finding shows that the EMG pattern underlying
      the axial synergies is flexible and that adaptive changes take place both under
      microgravity and after return to Earth.

PMID- 8275263
TI  - A predictive test for space motion sickness.
AB  - Eye torsion was examined in 13 astronaut subjects, tested during repeated
      episodes of 0 G and 1.8 G in parabolic flight aboard NASA's KC-135. Four findings
      are included. 1) A strong relationship between previous history of SMS and ocular
      torsional disconjugacy in novel gravitational states. 2) Responses were unchanged
      in 4 subjects retested a year later. 3) Ocular torsional disconjugacy scores
      increased as exposure to 0 and 1.8 G increased. This was particularly evident in
      subjects who had had SMS. 4) Torsional studies during 10 to 20 parabolas are
      required to accurately predict SMS. The hypothesis of otolith asymmetry,
      compensated in 1 G but becoming unmasked in novel gravitational states, is
      proposed to explain the torsional disconjugacy and ensuing SMS.

PMID- 8275264
TI  - Perceived self-orientation and self-motion in microgravity, after landing and
      during preflight adaptation training.
AB  - The research described in this paper is intended to support development and
      evaluation of preflight adaptation training (PAT) apparatus and procedures.
      Successful training depends on appropriate manipulation of visual and inertial
      stimuli that control perception of self-motion and self-orientation. For one part
      of this process, astronauts are trained to report their self-motion and self
      orientation experiences. Before their space mission, they are exposed to the
      altered sensory environments produced by the PAT trainers. During and after the
      mission, they report their motion and orientation experiences. Subsequently, they
      are again exposed to the PAT trainers and are asked to describe relationships
      between their experiences in microgravity and following entry and their
      experiences in the trainers.

PMID- 8275265
TI  - Crucial effects of weightlessness on human orientation.
AB  - This contribution examines the consequences of two remarkable experiences of
      subjects in weightlessness, 1) the missing of sensations of trunk tilt and of the
      respective concomitant reflexes when the head is tilted with respect to the
      trunk, and 2) the persistence of a perception of "up" and "down," that is, of the
      polarity of the subjective vertical (SV) in the absence of, as well as in
      contradiction to, visual cues. The first disproves that the necessary head-to
      trunk coordinate transformation be achieved by adding representations of the
      respective angles gained by utricles and neck receptors, but corroborates an
      extant model of cross-multiplication of utricular, saccular, and neck receptor
      components. The second indicates the existence of force-independent components in
      the determination of the SV. Although the number of subjects is still small and
      experimental conditions are not as homogeneous as desired, measurements and/or
      reports on the ground, in parabolic, and in space flight point to the decisive
      role of the saccular z-bias, that is, of a difference of the mean resting
      discharges of saccular units polarized in the rostrad and the caudad (+/- z-)
      direction.

PMID- 8275266
TI  - Horizontal angular VOR, nystagmus dumping, and sensation duration in spacelab SLS
      1 crewmembers.
AB  - In 1G, the apparent time constant (Td) of postrotatory SPV decay with the head
      tilted face down is 55% of that with head erect (Te). This phenomenon is called
      "nystagmus dumping" and has been attributed to G effects on VOR velocity storage.
      Similarly, postrotatory sensation duration with head tilted (Dd) is 32% of that
      when head erect (De). In parabolic flight, Te and De are 70% of 1-G values, but a
      pitch back dumping movement produces no further change. Te, Td, and Dd have not
      previously been measured in orbital flight. VOR and sensation duration was tested
      in 4 crewmembers in 4 preflight, 1 inflight (days 4 or 5) and 4 post flight
      sessions. Bitemporal EOG was recorded with eyes open in darkness. Instructions
      were to "gaze straight ahead," and indicate when "rotation sensation disappears
      or becomes ambiguous". Subjects were rotated CW and CCW head erect for 1 min at
      120 degrees/s, stopped, and EOG was recorded for another 1 min. This procedure
      was then used to study dumping, except that immediately after chair stop,
      subjects pitched their head forward 90 degrees. SPV was calculated using order
      statistic filtering, and dropouts removed using an iterative model fitting
      method. Te and Td were determined by logarithmic linear regression of mean SPV
      for each subject. In orbit, 90 degrees pitch movement produced rapid subjective
      dumping, but not nystagmus dumping. Dd was noticeably shorter ("almost
      instantaneous") compared to preflight Dd. Te and Td in orbit were similar to
      preflight Te for 3/4 subjects (rather than to preflight Td as expected). No
      consistent VOR gain changes were seen in orbit. Although Te is known to decrease
      acutely in parabolic flight, a longer time constant was measured in 3/4 subjects
      after 4-5 days adaptation to weightlessness, suggesting a return of angular
      velocity storage.

PMID- 8275267
TI  - Gaze control in microgravity. 1. Saccades, pursuit, eye-head coordination.
AB  - During the long-duration spaceflight Aragatz on board the Mir station, an
      experiment exploring the different oculomotor subsystems involved in gaze control
      during orientation to a fixed target or when tracking a moving target was
      executed by two cosmonauts. Gaze orientation: with head fixed, the "main
      sequence" relationships of primary horizontal saccades were modified, peak
      velocity was higher and saccade duration was shorter in flight than on earth,
      latency was decreased and saccade accuracy was better in flight. With head free,
      gaze orientation toward the target was achieved by coordinated eye and head
      movements, their timing was maintained in the horizontal plane; when gaze was
      stabilized on the target, there was a trend of a larger eye than head
      contribution not seen in preflight tests. Pursuit: Horizontal pursuit at 0.25 and
      0.5 Hz frequency remained smooth with a 0.98 gain and minor phase lag, on earth
      and in flight. In the vertical plane, the eye did not track the target with a
      pure smooth pursuit eye movement, but the saccadic system contributed to gaze
      control. Upward tracking was mainly achieved with a succession of saccades,
      whereas downward tracking was due to combined smooth pursuit and catch-up
      saccades. This asymmetry was maintained during flight in head fixed and head free
      situations. On earth, head peak velocity was maximal upward, and in flight it was
      maximal downward.

PMID- 8275268
TI  - Gaze control in microgravity. 2. Sequences of saccades toward memorized visual
      targets.
AB  - The reproduction, in complete darkness, of sequences of 5 horizontal saccades
      towards previously presented visual targets has been investigated in human
      subjects on the ground (control subjects) and one cosmonaut in microgravity. The
      incidence of corrective saccades during the execution of the memory-guided
      saccades in darkness has been examined. It was quite large for the control
      subjects (more than half of all saccades), and increased during the flight, while
      the corrective visually guided saccades incidence decreased. Direction errors
      occurred in about the third of all sequences on the ground, and this parameter
      also increased in microgravity. Memory-guided sequences were mostly hypermetric.
      Whereas the absolute error continuously increased with the target rank, it was
      not the case with the amplitude ratio, which presented a peak at the third rank,
      that is, at the middle of the sequence. The accuracy of the reproduction of the
      sequences did depend on the sequence pattern as much as on the subject. Some
      learning was observed in repeated reproduction of the same pattern. Although the
      average error did not change in microgravity, the linear regression coefficient
      between the visually guided and memory-guided saccades decreased.

PMID- 8275269
TI  - Multisensory, cognitive, and motor influences on human spatial orientation in
      weightlessness.
AB  - Exposure to weightlessness affects the control and appreciation of body position
      and orientation. In free fall the perception of one's own orientation and that of
      the surroundings is dependent on the presence or absence of contact cues, whether
      part of the body is visible in relation to the architecturally defined verticals
      of the space craft, cognitive factors, and exposure history. Sensations of
      falling are not elicited in free fall when the eyes are closed or the visual
      field is stabilized. This indicates that visual and cognitive factors as well as
      vestibular ones must be implicated in the genesis of such sensations under normal
      circumstances. Position sense of the limbs is also degraded in free fall. This
      may be due to alterations in skeletal muscle spindle gain owing to a decreased
      otolith-spinal activation. We provide evidence that during initial exposure to
      weightlessness there is a decrease in muscle stiffness which affects movement
      accuracy. The altered loading of the skeletal muscles due to the head and body
      being weightless are shown to be significant etiological factors in space motion
      sickness.

PMID- 8275270
TI  - Vestibular bibliography.

PMID- 8275271
TI  - Current view of the mechanism of benign paroxysmal positioning vertigo:
      cupulolithiasis or canalolithiasis?
AB  - Theoretical evidence is presented that all the typical features of BPPV (benign
      paroxysmal positioning vertigo) cannot be explained by cupulolithiasis in that
      otoconial debris become settled on the cupula of the posterior semicircular
      canal. A free floating clot of inorganic particles (heavier than endolymph) in
      the ampullofugal branch of the posterior semicircular canal is more likely to
      cause the syndrome. The clot always gravitates to the most dependent part of the
      canal as soon as the patient's head is moved in a way that alters the angle
      between the canal's plane and the gravity vector. As compared to a plunger
      (depending on the direction it moves) the clot produces push or pull forces on
      the cupula, thereby eliciting the BPPV attack. This clot-induced endolymph flow
      mechanism is compatible with all features of BPPV such as latency, limited
      duration, fatigability, change in direction of the induced nystagmus, and the
      efficacy of physical therapy in both posterior and horizontal semicircular canal
      BPPV. The floating clot is only activated by changes in position of the head
      relative to the gravitational vector (positioning vertigo) but not by prolonged
      static positions of the head (positional vertigo), which fits clinical
      experience. Therefore, canalolithiasis rather than cupulolithiasis provides a
      better definition of the underlying mechanism in BPPV.

PMID- 8275272
TI  - Dynamic posturography among patients with common neck disorders. A study of 15
      cases with suspected cervical vertigo.
AB  - We have studied a consecutive series of 15 patients with long-lasting common neck
      pain combined with vertigo and/or unsteadiness by dynamic posturography with the
      head in different positions. The evaluation of disturbed equilibrium was done in
      the anteroposterior direction. Results were compared with 15 sex- and age-matched
      healthy controls and 10 patients with long-lasting neck complaints without
      vertigo or unsteadiness. The otoneurological, audiometrical, and
      electronystagmographical examination was normal in all individuals. The dynamic
      posturography on a sway-referenced forceplate showed significantly lower
      equilibrium scores in the patients with vertigo/unsteadiness than in the controls
      when recorded in neutral position of the head, in rotation and in lateral
      flexion. The patients with vertigo also had significantly lower equilibrium
      scores in the position most prone to elicit their vertigo/unsteadiness as
      compared with the patients with only neck pain. Dynamic posturography was found
      to be of diagnostic value, indicating the presence of vertigo of cervical origin.

PMID- 8275273
TI  - Somatotopical effects of local microinjection of GABAergic agents in Deiters
      nucleus on the posturokinetic responses to cortical stimulation.
AB  - The postural adjustments that accompany the limb flexion following stimulation of
      the motor cortex in the cat are in part at least mediated by the lateral
      vestibular nucleus (LVN). In fact, inactivation of vestibulospinal (VS) neurons
      by unilateral injection of GABA agonists into the LVN decreased the early
      component of the responses in all of the postural limbs without modifying the
      threshold, latency, or amplitude of the cortically induced flexion movement. Just
      the opposite result was obtained after injection into the same structure of GABA
      antagonists. Experiments were performed to find out whether these VS influences
      were somatotopically organized. Microinjection of 0.25 microL of the GABA-A
      agonist muscimol or the GABA-B agonist baclofen (at 1.5 to 4 micrograms/microL
      saline) into the rostroventral part of the LVN (rvLVN) of one side produced
      hypotonia in the ipsilateral and hypertonia in the contralateral forelimb. The
      same injection also reduced the early component of the postural responses to
      cortical stimulation in both forelimbs, but not in the hindlimbs. On the other
      hand, unilateral injection of the same agents into the dorsocaudal part of the
      LVN (dcLVN) produced similar effects, but they were limited to the hindlimbs. The
      results obtained, which lasted for about 2 to 3 h, were not only site-specific
      but were also dose-dependent. Injection into the rvLVN or dcLVN of 0.25 microL of
      the GABA-A antagonist bicuculline or the GABA-B antagonist phaclofen (at 8 or 5
      micrograms/microL saline) produced localized changes in posture as well as in the
      post-urokinetic responses to cortical stimulation. These were opposite in sign to
      those elicited by the corresponding agonists. In conclusion, it appears that: 1)
      the motor cortex utilizes descending volleys passing through the LVN in order to
      elicit the early postural adjustments during a cortically induced limb movement;
      2) the resulting VS influences are somatotopically organized; 3) the amplitude of
      these postural responses can be affected by inhibitory influences probably
      exerted by Purkinje cells of the cerebellar vermis on the related VS neurons
      through both GABA-A and GABA-B receptors.

PMID- 8275274
TI  - Effect of sway-referenced visual and somatosensory inputs on human head movement
      and postural patterns during stance.
AB  - The purposes of this study were to (1) evaluate the effects of sway-referenced
      visual and ankle somatosensory inputs on head movement and body sway during
      stance and (2) determine how sway-referenced sensory inputs might influence the
      selection of postural patterns. Seventeen healthy adult subjects were evaluated
      while attempting to maintain standing balance. Ankle somatosensory inputs were
      altered during stance by creating support surface rotations which were
      continuously adjusted ("referenced") to the center of force. In selected trials,
      ankle somatosensory or visual inputs were distorted further by increasing the
      platform/body sway gain or by increasing the sway-referenced gain of a rotating
      visual enclosure. The results showed that spontaneous body sway in a given
      direction was generally associated with head displacement in the opposite
      direction. The slope of the sway vs. sagittal head position linear regression
      line was statistically greater at a sway-referenced gain of 1.5 compared to a
      gain of 1.0. This finding was observed specifically when mechanical compliance of
      the support surface was increased and occurred whether the eyes were open or
      closed. Horizontal shear force was generated in the same direction as head
      displacement and the linear regression slope was greatest with eyes open and at a
      sway gain of 1.5. These findings indicate that (1) destabilization of the ankles
      altered displacement of the head independently from visual input, and (2) visual
      information was necessary to produce specific postural patterns utilizing
      horizontal shear forces to maintain stance on a mechanically compliant surface.
      The results provide evidence for a neural mechanism linking ankle somatosensory
      inputs and head control.

PMID- 8275275
TI  - Predictors of less stable postural responses to support surface rotations in
      healthy human elderly.
AB  - Balance corrections elicited in response to a rotation of the support-surface
      were compared between healthy elderly and young normal subjects using surface EMG
      records from the soleus, tibialis anterior, and neck extensor muscles, and
      measurements of trunk angular acceleration and ankle torque. Three differences
      were observed. First, EMG response latencies were significantly longer in the
      elderly. Second, the normal linear correlation between stabilizing ankle muscle
      activity and ankle torque was disturbed. These two differences were presumably
      responsible for the diminished ankle torque exerted on the support surface by the
      elderly subjects. Third, the magnitude of neck muscle activation was increased in
      elderly subjects, indicating an increased compensation at the head for trunk
      angular acceleration. The findings suggest that there are both neural and
      mechanical changes that may impact on postural corrections in elderly subjects,
      and that more than one factor needs to be identified when predicting an
      individual's risk for falling.

PMID- 8275276
TI  - Non-corticotropic ACTH peptides modulate nerve development and regeneration.
AB  - Short peptide sequences of ACTH 1-39 (the ACTH 4-9 analog Org 2766, ACTH 4-10 and
      its analog BIM 22015, and ACTH 1-13 [alpha-MSH]), which do not stimulate the
      adrenal cortex, have profound effects on the developing and regenerating
      neuromuscular system, in neonatal and in adult rats. Both development and
      regeneration are accelerated, as indicated by improved morphological,
      electrophysiological, behavioral and biochemical parameters. Regeneration in the
      central nervous system is problematic but the ACTH peptides may provide
      protection for CNS neurons, enhance denervation sensitivity or permit
      compensatory processes which facilitate functional recovery. Neuronal cells in
      culture respond to ACTH peptides by greater neurite outgrowth, and in some cell
      types, by increased B-50 expression. In all cases, susceptibility to ACTH peptide
      treatment varies with cell type, age, the specific peptide administered, its
      dosage and pattern of administration. External stress and the gender of the
      animal are additional factors that interact with the neurotrophic actions of the
      melanocortins.

PMID- 8275277
TI  - Physiological consequences of the passage of peptides across the blood-brain
      barrier.
AB  - Peptides given peripherally have been shown to affect the central nervous system
      (CNS). Peptides are also capable of crossing the blood-brain barrier (BBB). It is
      unclear, however, whether such crossing underlies the ability of peptides to
      affect the CNS. We review specific examples in which a peptide must cross the BBB
      to produce its effect. The effect elicited by passage often duplicates the effect
      elicited at peripheral sites of action. Other examples, however, are reviewed in
      which peptides have opposite effects after central and peripheral administration.
      Such paradoxical effects suggest that passage of peptides may be involved in
      feedback or counter-regulatory loops.

PMID- 8275278
TI  - Involvement of opioid mechanisms in the dorsal periaqueductal gray in drug abuse.
AB  - The opiate abstinence syndrome is comprised of motivational symptoms and physical
      correlates. In rats, physical correlates have been characterized as intense
      hyperactivity together with jumping, ptosis, teeth chattering, wet dog shakes,
      and diarrhea. Motivational symptoms have often been associated with the
      development of place aversions. The search for the neural substrates for the
      motivational symptoms and physical correlates of the opiate withdrawal syndrome
      has not reached a consensus as to the existence of a common or separate neural
      basis responsible for them. In our laboratory, we have gathered evidence that
      microinjection of morphine into the DPAG inhibits defensive behaviors. However,
      DPAG microinjections of high doses may produce a 'fearful' hyperactivity as
      measured in a circular arena or produce anxiogenic-like effects as measured in
      the elevated plus maze. The antiaversive effects of morphine result from its
      action on mu receptors and the aversive ones may be associated with its action on
      other opiate receptors. These findings implicate the PAG as an important
      structure of the neurobiological substrate of the emotional and physical
      correlates of the opiate abstinence syndrome.

PMID- 8275279
TI  - Application of confocal laser scanning microscopy to analysis of H2O2-induced DNA
      damage in human cells.
AB  - Confocal laser scanning microscopy (CLSM) offers improved depth discrimination
      and spatial resolution to the analysis of biologic samples. We demonstrate in
      this paper that such technology is valuable in examining DNA single-strand breaks
      in human cells. The single-cell-gel (SCG) assay is a new technique for measuring
      DNA strand breaks in individual cells. Cells embedded in low-melting-point
      agarose are treated with varying concentrations of hydrogen peroxide to induce
      DNA strand breaks. Following cell lysis and alkaline electrophoresis, which
      enables single-stranded break detection, analysis of the resulting "comets"
      provides an accurate method of comparing changes in DNA migration patterns, which
      have been shown to reflect the DNA damage levels. A statistically significant
      difference (p < 0.01) in single-stranded DNA damage levels was detected in cells
      exposed to hydrogen peroxide concentrations as low as 10 nm for 2 min. LSM
      analysis of the SCG technique allows rapid, sensitive, and reproducible
      quantitation of single-stranded breaks of cellular DNA.

PMID- 8275280
TI  - Accreditation of psychotherapists.

PMID- 8275281
TI  - Psychological impact of chronic neurological disease.

PMID- 8275282
TI  - Management of the child with cystic fibrosis.
AB  - The association between salty skin and early death has been recognized since
      medieval times but the first description of cystic fibrosis was not published
      until 1938 by Anderson. Over teh last 53 years attitudes to the disease have
      changed radically and modern aggressive care involving a wide variety of
      professionals has contributed to the improved life expectancy.

PMID- 8275283
TI  - Preventing strokes in non-rheumatic atrial fibrillation.
AB  - Almost 1 in 10 patients with non-rheumatic atrial fibrillation is at risk of
      stroke. This article describes the risk factors and assesses the role of aspirin
      and warfarin in stroke prevention.

PMID- 8275284
TI  - Medical approach to rhinitis.
AB  - Rhinitis is a common and important cause of morbidity and impairment of quality
      of life. An accurate diagnosis, although usually straightforward, is important
      before commencing treatment. There have been major advances in diagnostic aids,
      including specific allergen extracts for skin testing, computed tomography of the
      nose and paranasal sinuses and the availability of flexible and rigid
      rhinoscopes. Advances in treatment include the availability of topical
      corticosteroids and non-sedative antihistamines, and the use of minimally
      invasive surgical techniques. Immunotherapy retains a place in carefully selected
      pollen-sensitive patients.

PMID- 8275285
TI  - Emla cream and its current uses.
AB  - The use of Emla cream in the 1980s has enabled many procedures to be carried out
      without unnecessary pain or discomfort. Its various potential uses have been
      evaluated in many different specialties. This article reviews the application of
      Emla that have been found to be effective.

PMID- 8275286
TI  - A reappraisal of steroid-induced osteoporosis.
AB  - The anti-inflammatory and immunosuppressive effects of corticosteroids were first
      recognized by Hench and colleagues in 1949. It soon became apparent that
      supraphysiological doses were associated with numerous side effects, particularly
      osteoporosis and skeletal failure. In spite of this, the pathogenesis of steroid
      osteoporosis remains unclear and its prevention and treatment controversial.

PMID- 8275287
TI  - Objectives of basic surgical training.
AB  - There are a range of skills to be learned in basic surgical training. These
      include communication and patient management, operating and other technical
      skills, and audit. Surgical tutors might use such a framework to facilitate
      education and assessment of their trainees.

PMID- 8275288
TI  - Principles of patient management.
AB  - The more satisfied the patient is with the consultation the higher the
      probability that he will comply with the doctor's advice. Doctors should
      therefore be familiar with the principles of patient management and how to
      implement them during the consultation.

PMID- 8275289
TI  - Giant epidermoid cyst near the anterior fontanelle.

PMID- 8275290
TI  - Hazards of fad diets in patients treated with ACE inhibitors.

PMID- 8275291
TI  - Resuscitation in a shocked infant.

PMID- 8275292
TI  - Potential problems in the day surgery unit.

PMID- 8275293
TI  - The incontinent woman: 2.
AB  - The second article in this two-part series deals with the diagnosis and treatment
      of urinary incontinence in women. This encompasses genuine stress incontinence,
      detrusor instability and sensory urgency. These can be effectively treated with
      careful understanding of the patient's symptomatology and objective diagnosis.

PMID- 8275294
TI  - Direct delivery of health services to children.

PMID- 8275295
TI  - Hormonal management of prostatic cancer.

PMID- 8275296
TI  - No smoke without ire.

PMID- 8275297
TI  - Stimulus speed and order of presentation effect the visually released predatory
      behaviors of the praying mantis Sphodromantis lineola (Burr.).
AB  - To assess the role of stimulus speed and order on the predatory behaviors of the
      praying mantis Sphodromantis lineola (Burr.), tethered adult females were
      presented with various flat black stimuli (lures) by means of a variable speed
      mechanical arm. Lure speed had a dramatic effect on mantis behavior: mantises
      emitted significantly more strikes to a 6 x 6 mm square and to 'worm' lures (i.e.
      length > width = 6 mm) moving at 34.3 cm/sec than they did to 'antiworm' lures
      (i.e. width > length = 6 mm), or to slower moving lures. These effects were
      consistent over lure directions (0-75 degrees relative to the mantis' long axis),
      and background patterns. On the other hand, mantises emitted significantly more
      approaching behavior to lures moving at 12 cm/sec than to lures moving at 36
      cm/sec. This suggests that S. lineola extract distance information from retinal
      image velocity, as do other insects. Stimulus order also effected mantis
      predatory behavior: for instance, mantises were more likely to track a lure
      without striking at it on the first trial than on subsequent trials. However,
      after the first trial, they were also more likely to freeze (become immobile)
      when a lure was presented. Mantises were also less likely to strike at a
      preferred lure if it was preceded by one or two non-preferred lures. In a final
      experiment, intact, freely moving mantises were placed in an arena, presented
      with adult crickets, and video taped. The behaviors of the freely moving mantises
      were congruent with those of the tethered mantises in the previous experiments.
      This series of experiments demonstrates that the information processing
      capabilities of S. lineola are more complex than generally depicted, however,
      they can be explained by assuming a neural organization similar to that of other
      insects such as flies (Diptera) and dragonflies (Odonata).

PMID- 8275298
TI  - The visual system of the Florida garfish, Lepisosteus platyrhincus (Ginglymodi).
      III. Retinal ganglion cells.
AB  - The vitreal vascularization, optic nerve fiber layer and the retinal ganglion
      cells are examined in the Florida garfish, one of the two surviving genera of the
      ginglymode group of actinopterygian fishes. In the absence of a choroidal gland,
      a well developed system of hyaloid blood vessels overlie the inner retina. The
      optic nerve fiber and ganglion cell layers are integrated to form a series of
      alternating columns or fascicles emanating from an elongated optic nerve head.
      Horseradish peroxidase or cobaltous lysine infusion from the optic nerve reveals
      seven ganglion cell classes based on soma size and position, dendritic field
      size, retinal coverage and terminal stratification. Two discrete populations of
      giant ganglion cells with large somata and large dendritic fields stratify either
      within the sclerad region (type I cells) and/or within the middle region (type 2
      cells) of the inner plexiform layer. Both giant ganglion cell populations (1% of
      total) form evenly distributed arrays with the dendritic arbor of each type
      covering the retina completely. Between seven and nine type 2 cells overlap the
      dendritic field of a single type 1 cell. Type 3 cells are small and located in
      the inner nuclear layer with a multistratified dendritic field terminating
      throughout the inner plexiform layer. Topographic analysis of the population of
      type 3 cells (4% of total) reveals a temporal area centralis (6.25 x 10(2) cells
      per mm2) and a ventral horizontal streak (6.25 x 10(2) cells per mm2). The large
      population of cells within the ganglion cell layer are classified as types 4, 5
      and 6 based on soma size, dendritic field size and dendritic stratification and
      collectively these cells match the distribution of ganglion cells within the
      inner nuclear layer with 5.3 x 10(3) cells per mm2 in the temporal area centralis
      and 8.6 x 10(3) cells per mm2 in the horizontal streak. Type 7 cells possess
      small somata and send branches into both the inner and outer plexiform layers and
      have been termed biplexiform ganglion cells. Phylogenetic comparisons of several
      morphological features of the garfish retina reveals the polarity, conservation
      and the evolution of a number of visual characters.

PMID- 8275299
TI  - Areal, modular, and connectional organization of visual cortex in a prosimian
      primate, the slow loris (Nycticebus coucang).
AB  - Slow lorises (Nycticebus coucang) are nocturnal prosimian (i.e. strepsirhine)
      primates, closely related to bushbabies (Galago spp.). We examined the
      organization of visual cortex in four hemispheres from two slow lorises, using
      connectional and architectonic techniques. All hemispheres were flattened and
      sections stained for myelin and cytochrome oxidase (CO). Our results indicate,
      first, that the primary visual area (V1) in slow lorises has a system of small CO
      dense blobs, as has been described in most other anthropoid and prosimian
      primates examined to date. The second visual area (V2) is characterized by broad,
      stripe-like zones of dense CO staining separated by zones of lighter staining.
      Loris V2 stripes are less distinct than those of anthropoid primates, and
      separate classes of thin and thick dark stripes are not apparent. However, V2
      stripes are much better developed than in Galago, where they are virtually
      absent. Injections of wheat-germ agglutinin conjugated to horseradish peroxidase
      (WGA-HRP) in area V1 revealed reciprocal connections with area V2, and the middle
      temporal (MT) and dorsolateral (DL) extrastriate areas. Area MT was also
      identified by its distinctive, dense myelination. As has been reported in
      anthropoids, DL can be divided into separate caudal and rostral divisions, which
      differ in myelin and CO staining, and in the strength of their connections with
      V1. Taken together, our results suggest that many of the features that
      characterize visual cortex organization in anthropoid primates are present in
      prosimians and thus probably evolved early in primate history, prior to the
      diversification of modern primate groups.

PMID- 8275300
TI  - The ontogeny of inter- and intrasexual vocal muscle dimorphisms in a sound
      producing fish.
AB  - This study documents the development of inter- and intrasexual dimorphisms in the
      vocal ('sonic') muscles of the swimbladder in the plainfin midshipman fish,
      Porichthys notatus. Midshipman have two male reproductive morphs, Types I and II.
      Only Type I males build nests and generate mate calls to attract females; Type II
      males sneak or satellite spawn. Vocal muscles in the mate-calling Type I males
      were 25-fold larger in absolute size (sixfold larger when scaled to body size)
      compared with females or non-calling Type II males. Dimorphisms in muscle mass
      were correlated with dimorphisms in fiber number and diameter. Only nascent Type
      I males experienced a pre-maturational, fourfold increase of fiber number
      followed by a rapid, fivefold increase in fiber cross-sectional area at sexual
      maturity. Also specific to Type I males was a striking change in cell structure:
      the ratio of sarcoplasm to myofibril area increased fivefold. By contrast, Type
      II males and females matured without showing any of these changes in sonic muscle
      -the trajectories which described juvenile growth continued to hold through
      maturity and adulthood. The results indicate distinct, non-sequential,
      ontogenetic trajectories for Type I and Type II males. The origin of the Type II
      male morphotype is described as paedomorphosis by progenesis: size distributions
      of free-living animals suggest that Type II males can mature precocially as one
      year-old fish, whereas Type I males defer reproduction until they are at least
      two years of age.

PMID- 8275301
TI  - Unchanged [3H]MK-801 binding and increased [3H]flunitrazepam binding in turtle
      forebrain during anoxia.
AB  - In order to determine if functional changes in N-methyl-D-aspartate receptors and
      GABAA receptors play a role in the remarkable anoxia tolerance of freshwater
      turtle brain, we used autoradiographic techniques to assay [3H]MK-801 and
      [3H]flunitrazepam binding in turtle forebrain after turtles had been subjected to
      anoxia for 2 or 6 h. The effects of glutamate, glycine, competitive N-methyl-D
      aspartate antagonists, glycine antagonists, polyamines, magnesium, and zinc on
      [3H]MK-801 binding were the same in anoxic and control turtle forebrains. These
      results indicate that NMDA receptor regulation plays no role in the adaptive
      responses to anoxia in turtle brain. In contrast, [3H]flunitrazepam binding was
      significantly increased in the anoxic dorsal cortex and striatum. The most
      parsimonious explanation for elevated benzodiazepine receptor binding is that the
      rise in extracellular GABA levels known to accompany anoxia enhances
      benzodiazepine receptor affinity. It is possible, however, that GABAA receptor
      upregulation during anoxia increases the effectiveness of the inhibitory action
      of released GABA and contributes to the anoxia tolerance of turtles.

PMID- 8275302
TI  - MHC class II antigen expression and T-cell infiltration in the demyelinating CNS
      and PNS of the twitcher mouse.
AB  - The expression of the major histocompatibility complex class II antigens (Ia) was
      investigated in the central and peripheral nervous systems of the twitcher mouse,
      an authentic murine model of globoid cell leukodystrophy (Krabbe disease) in
      humans. In this mutant, demyelination is noted as early as postnatal day 10 in
      the peripheral nerve and day 20 in the spinal cord. Emergence of Ia antigen
      expressing cells (Ia+ cells) was largely coincident with the initiation of
      demyelination, suggesting the importance of local factors for the induction of Ia
      antigens. Ia+ cells gradually increased in number with the progression of
      demyelination, but reached a plateau between postnatal days 30 and 40, then
      rapidly decreased despite continuous demyelination in both central and peripheral
      nervous systems. The only exception was in the spinal cord where Ia+ cells were
      numerous even at postnatal day 50. The cells expressing L3T4 antigen (L3T4+
      cells), which is a mouse CD4 antigen, and the interleukin-2 receptor antigen
      expressing cells (IL-2R+ cells), also appeared in the regions where Ia+ cells
      were observed. L3T4+ cells were still abundant after P45, when Ia+ and IL-2R+
      cells decreased. Combined autoradiographic and immunocytochemical studies
      demonstrated mitotic activity in a few Ia+ cells. However, low labeling indices
      of Ia+ cells in both cerebrum and sciatic nerve suggest that the increase of Ia+
      cells was largely due to either induction of Ia antigens on local cells or new
      recruitment of Ia+ cells from the circulation. Expression of Ia antigens
      associated with an emergence of L3T4+ or IL-2R+ cells in the demyelinating
      lesions may indicate involvement of immunological responses in the pathogenesis
      of this metabolic demyelinating disorder. Alternatively, these apparent
      immunological phenomena may be tentative and non-specific local reactions to
      degenerating tissue components such as myelin. The mechanism(s) regulating the
      expression of Ia antigens in this genetic metabolic demyelinating disease is yet
      to be determined.

PMID- 8275303
TI  - Effect of protein malnutrition on CA3 hippocampal pyramidal cells in rats of
      three ages.
AB  - Prenatal and postnatal protein deprivation effects on CA3-hippocampal pyramidal
      cells were investigated in 30-, 90- and 220-day-old rats. Female rats were fed
      either a 6% or a 25% casein diet 5 wk before conception and the litters were
      maintained on their respective diet until sacrificed. In 216 rapid Golgi
      impregnated cells, we measured somal size, length and diameter of apical
      dendrite, number of apical dendrites intersecting 10 concentric rings 38 microns
      apart, thorny excrescence area and length, head diameter and density of synaptic
      spines on 50-microns segments of apical dendrite. The present experiments showed
      that malnutrition produced significant reductions of somal size in animals at 220
      days of age. There were significant reductions of apical dendrite diameters in
      animals of 30 and 90 days, and of density and head diameter of synaptic spines at
      the three ages studied, and significant decrease of the thorny excrescence area
      at 220 days of age. At this latter age, dendritic branching was significantly
      decreased in the last four rings representing the area into which the perforant
      pathway projects. In 30-day malnourished rats, dendritic branching showed a
      significant increase in rings 4-6 representing the area in which the Schaffer
      collaterals synapse. The location of the deficit in dendritic spines corresponds
      to the sites where mossy fibers synapse on the apical dendrites of CA3 neurons.
      Age-related changes normally observed in control rats (e.g., the 30-day-old
      control group showed the smallest somal size and 220-day-old controls the largest
      size) failed to occur in the malnourished rats. The deficits in spine density and
      dendritic branching (in animals of 220 days old) were similar to those found in
      our previous studies on fascia dentata.

PMID- 8275304
TI  - Corticotropin-releasing hormone microinfusion in the central amygdala diminishes
      a cardiac parasympathetic outflow under stress-free conditions.
AB  - The central nucleus of the amygdala (CeA) is known to be involved in the
      regulation of autonomic, neuroendocrine and behavioural responses in stress
      situations. The CeA contains large numbers of corticotropin-releasing hormone
      (CRH) cell bodies. Neuroanatomical studies revealed that the majority of the CRH
      fibres from the CeA have direct connections with autonomic regulatory nuclei in
      the brainstem. In the present study, the effects of locally infused CRH (30 ng)
      into the CeA, in freely moving male Wistar rats under stress-free conditions,
      were examined. Heart rate, endocrine parameters and behavioural activity were
      repeatedly measured before, during and after local administration of CRH,
      pretreated with either artificial CSF or the CRH-receptor antagonist, alpha
      helical CRH (alpha-hCRH). CRH infusion alone caused a long-lasting increase in
      heart rate without affecting plasma adrenaline and noradrenaline as indicators of
      sympathetic activity. This CRH-induced tachycardia was effectively blocked by
      pretreatment with a high dose (1 microgram) alpha-hCRH locally into the CeA,
      while the pretreatment with low dose (0.1 microgram) of the alpha-hCRH caused a
      minor blockade of the CRH-induced tachycardia. The results suggest that CRH
      mechanisms in the CeA regulate the autonomic changes probably only by affecting
      parasympathetic but not sympathetic output systems. Because CRH is given at the
      level of the cell body of the CRH neurons in the CeA, we suggest that the
      reduction of the parasympathetic output may be explained as an autoreceptor
      mediated inhibition of CRH neurons from the CeA with parasympathetic-regulating
      brainstem nuclei.

PMID- 8275305
TI  - Identification and distribution of axonal dystrophic neurites in Alzheimer's
      disease.
AB  - Dystrophic neurites (DNs) are one of the neuropathological characteristics of
      Alzheimer's disease (AD). Previously, it has been suggested that tau
      immunoreactive DNs are of dendritic origin and that axonal and dendritic
      dystrophic neurites are morphologically indistinguishable. In the present study,
      two monoclonal antibodies, tau-1 and PHF-1, were used to examine sections of the
      hippocampal formation from AD and normal aged brains. Both antibodies stained
      dendritic DNs as well as axonal DNs. Axonal DNs were clearly seen in axonal fiber
      tracts, white matter and hippocampal terminal regions. Axonal DNs arising from
      neurofibrillary tangles were easily detected in CA3 and CA1. The morphological
      appearance of axonal DNs varied with the neuron type from which it originated.
      The most distinctive feature of tau-1 or PHF-1 immunostained axonal DNs was their
      uneven contour, alternating swollen and shrunken segments and short rod or cone
      shaped fragments. In contrast, dendritic dystrophic neurites are thicker and more
      tortuous. It appears that while DNs are both dendritic and axonal in origin,
      axonal DNs are more prevalent and widespread in the AD brain than previously
      realized and may represent one of the main pathological lesions in AD.

PMID- 8275306
TI  - Neuronal beta-amyloid precursor protein gene expression: regulation by
      aurintricarboxylic acid.
AB  - beta-Amyloid precursor protein (beta-APP) and its derivative, amyloid beta
      protein (beta-A4), may cause death of differentiated neurons and
      aurintricarboxylic acid (ATA), a metabolic inhibitor, improves neuronal survival.
      Therefore, we studied the effect of ATA on neuronal beta-APP gene expression. ATA
      decreased beta-APP mRNA levels by increasing its degradation, without changing
      the rate of transcription. ATA decreased both steady state and interleukin-1
      (IL1)-induced increase in beta-APP mRNA levels. These effects of ATA were
      associated with rounding of cells suggestive of decreased cell adhesion or
      neurite retraction that was completely reversible when ATA was removed. However,
      beta-APP mRNA levels continued to remain suppressed in neurons that were actively
      regrowing neurites following discontinuation of ATA. In studies carried out upto
      24 h, ATA did not damage cells as determined by Trypan blue exclusion, lactate
      dehydrogenase (LDH)-release and transmission electron microscopy. The findings
      suggest that constitutive or steady state levels of beta-APP mRNA may not be
      essential for the survival and growth of neurons and that ATA suppresses beta-APP
      expression without causing cell damage. These observations may be a basis for
      studying whether ATA or a related compound could beneficially regulate beta-APP
      levels in vivo.

PMID- 8275307
TI  - Age-related changes of noradrenergic-NPY interaction in rat brain:
      norepinephrine, NPY levels and alpha-adrenoceptors.
AB  - Noradrenergic-neuropeptide Y interaction, which is implicated in different
      physiological functions, was studied in senescent rats. Norepinephrine (NE) and
      neuropeptide Y (NPY) levels were measured in brainstem and hypothalamus, and
      alpha-adrenergic binding was investigated in brainstem in young (4 months) and
      old (34 months) Wistar rats. NE concentration was the same in senescent rats,
      whereas NPY concentration was decreased both in brainstem and hypothalamus
      compared to levels in young rats. [3H]prazosin binding to alpha 1-adrenoceptors
      was not modified, but [3H]rauwolscine binding to alpha 2-adrenoceptors was
      altered with age. In fact, the density of alpha 2-adrenoceptors (Bmax) was lower,
      while the binding affinity (Kd) was increased in old compared to young rats.
      These results suggest that the decrease of NPY levels could be one of the
      possible reasons for changes in [3H]rauwolscine binding to alpha 2-adrenoceptors
      in old rats. The G-protein-adenylate cyclase system, which is impaired in
      senescent rats, could be involved in the disorganization of noradrenergic-NPY
      interaction.

PMID- 8275308
TI  - Serotonergic lesions decrease mu- and delta-opiate receptor binding in discrete
      areas of the hypothalamus and in the midbrain central gray.
AB  - Serotonergic nerve terminals in the brain were lesioned by intraventricular
      infusion of the selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) and levels
      of mu- and delta-opiate binding were measured in brain areas implicated in
      reproductive behavior and gonadotropin secretion. The lesion decreased mu
      receptor binding in the preoptic area (mPOA) and the midbrain central gray, while
      delta-receptor binding was decreased in the mPOA and the dorsomedial nucleus of
      the hypothalamus. Hypothalamic serotonergic lesions also attenuated morphine
      inhibition of female sexual behavior. These results indicate the existence of
      serotonergic-opiate interactions in select regions of the brain and suggest that
      these interactions may be important in the regulation of lordosis behavior.

PMID- 8275309
TI  - Changes in brain dopamine receptors in MPTP parkinsonian monkeys following L-dopa
      treatment.
AB  - Twenty-two monkeys (Macaca fascicularis) were utilized in this study. Ten animals
      were rendered parkinsonian with serial injections of MPTP (1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine). Five of these parkinsonian monkeys received L
      dopa/carbidopa treatment, and five animals did not. The remaining twelve animals
      did not receive MPTP. Eight of these animals received no L-dopa treatment, two
      animals were treated chronically with L-dopa/carbidopa and two animals received L
      dopa/carbidopa only on the day of sacrifice. All animals were given weekly scored
      neurologic examinations throughout the study. Their movement was quantitated in
      an activity box. All animals were sacrificed by an overdose of sodium
      pentobarbital. The parkinsonian animals were sacrificed 107-355 days after their
      last MPTP injection. The brains were removed and frozen. Punch samples were taken
      from the caudate and putamen for tissue dopamine determination. Selected areas of
      the basal ganglia were cut into 20 microns sections for quantitative receptor
      autoradiography. The density of D1 and D2 receptors was evaluated in the basal
      ganglia of these animals at the level of the anterior commissure. For the D2
      assay, total binding was determined using various concentrations of [3H]spiperone
      in buffer containing 300 nm mianserin. For the D1 assay, total binding was
      determined using various concentrations of [3H]SCH-23390. Tissue isotope
      concentration was determined from the autoradiographs. The MPTP parkinsonian
      monkeys showed a mean striatal dopamine depletion of 93.5% and a mean clinical
      score of 9.0. The untreated parkinsonian monkeys demonstrated an increase in the
      number of D2 sites as compared to controls. This increase was greatest in the
      lateral putamen.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275310
TI  - The ontogeny of seizures in a rat model of limbic epilepsy: evidence for a
      kindling process in the development of chronic spontaneous seizures.
AB  - Kindling is an experimental model for epilepsy in which repeated stimuli induce
      longer electrographic seizures and eventually cause behavioral convulsions.
      Although kindling has some features that are similar to chronic human epilepsy,
      it is not known whether this process plays a role in the development of chronic
      seizure disorders. We have recently described a rat model of chronic spontaneous
      limbic seizures that has a number of similarities to human limbic epilepsy. To
      determine whether a kindling process is involved in the ontogeny of the seizures
      in this animal model, we continuously monitored 16 rats with EEG and closed
      circuit television until they had experienced a minimum of 5 and as many as 10
      seizures following the first motor seizure. All animals had at least one non
      motor seizure before the first motor event (mean 5.1 +/- 0.9 S.E.M. initial non
      motor seizures, range 1-12). In addition the seizures significantly lengthened in
      duration with succeeding events (mean 90 s for the first motor seizure to mean
      110 s for the tenth subsequent seizure). These data demonstrate that there is a
      kindling process involved in the early development of chronic limbic seizures.

PMID- 8275311
TI  - Effect of nimodipine on the autoregulation of cerebral blood flow studied by
      laser-Doppler flowmetry.
AB  - The present work examines whether nimodipine impairs autoregulation of CBF during
      hypotension. The CBF of 16 anesthetized rabbits was measured with a laser-Doppler
      flowmetry probe placed on the external surface of a plexiglas window, chronically
      inserted in the skull. Autoregulation was triggered by aortic bleeding. First,
      the effects of three doses of nimodipine (1, 3 and 10 micrograms/kg) and the
      solvent were studied in 10 rabbits in which MABP was maintained at 50 mmHg for
      one minute. Second, 10 micrograms/kg i.v. nimodipine was administered to 6
      rabbits in which MABP was kept at 30 mmHg for one minute. Before bleeding, the 10
      micrograms/kg dose significantly decreased MABP (from 96 +/- 11 mmHg to 81 +/- 11
      mmHg, P < 0.01) and increased CBF (from 104 +/- 20% to 147 +/- 25%, P < 0.01) as
      compared to the solvent. In the first set of experiments, only the 10
      micrograms/kg dose suppressed the autoregulatory vasodilation, but CBF was not
      different from control (84 +/- 17% versus 87 +/- 12%), probably because of the
      previous induced vasodilation. In the second set of experiments, active
      vasodilation occurred and the CBF during hypotension was not different from
      control (72 +/- 26% versus 65 +/- 11%). We conclude that under nimodipine the
      triggering of the active autoregulatory vasodilation is dependent on both the
      severity of hypotension and the previous nimodipine-induced vasodilation.

PMID- 8275312
TI  - Paralytic tremor (pt) rabbit: a sex-linked mutation affecting proteolipid protein
      gene expression.
AB  - Paralytic tremor (pt) is a neurological sex-linked recessive mutation in rabbits
      which is characterized by a coarse body tremor and limb paresis. Morphological
      studies showed that this mutation affects CNS myelination. Although the number of
      oligodendrocytes is not reduced, myelination is slower, irregular and defective.
      We have made a biochemical and molecular analysis of 4-wk-old mutant and normal
      rabbits. The amount of myelin in the mutant represents only approximately 25% of
      the normal level. Radioimmunoassay for myelin basic protein showed a reduction to
      approximately 40% in pt whole-brain homogenate but the difference was not
      significant in purified myelin. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis of brain homogenates followed by immunoblotting showed that all
      major myelin proteins are affected by the pt mutation, although to different
      degrees. While most of the myelin proteins are reduced to approximately 60-80% of
      the normal level, an important reduction to approximately 30%, was measured for
      the proteolipid protein (PLP). In purified myelin, the difference in PLP
      concentration was significant while the other specific proteins were less
      affected. A similar reduction in myelin-protein gene expression was detected at
      the mRNA level. Sex-linked transmission, low concentrations of PLP and its
      specific mRNA in the CNS indicate that the pt mutation primarily affects the
      expression of the Plp gene.

PMID- 8275314
TI  - Heparin prevents M-current over-recovery but not M-current suppression in
      bullfrog sympathetic ganglion neurones.
AB  - The excitatory actions of G-protein-coupled agonists on amphibian sympathetic
      ganglion cells involve suppression of a voltage and time dependent, non
      inactivating K(+)-current called the M-current. Suppression of this current by
      muscarine or peptides is followed by a phase of 'over-recovery' during which the
      M-current exceeds its original level. Whilst it has been suggested that release
      of intracellular Ca2+ following the agonist-induced liberation of inositol 1,4,5
      trisphosphate is involved in the suppression phase of the response, another
      hypothesis suggests that the agonist-induced elevation of intracellular Ca2+ may
      account for M-current 'over-recovery'. The present study supports the latter
      hypothesis because intracellular application of the inositol 1,4,5-trisphosphate
      antagonist, heparin (150 microM), had little or no effect on muscarine-induced M
      current suppression whilst the 'over-recovery' phase of the response was markedly
      attenuated.

PMID- 8275313
TI  - Morphological differentiation of neuropeptide Y neurons in aggregate cultures of
      dissociated fetal cortical cells: a model system for glia-neuron paracrine
      interactions.
AB  - The temporal changes in the morphological profiles of neuropeptide Y (NPY)
      neurons and their topographical relationship with glial cells (astrocytes) were
      characterized in aggregate cultures derived from fetal cortical tissue using
      immunocytochemical procedures. On day 6 of culture, structures labelled with NPY
      antibodies were small and uneven in size but many resembled neuronal cell bodies.
      On day 14, neuronal perikarya were well defined and several morphological types
      of NPY neurons could be distinguished most of which gave rise to beaded
      processes: unipolar or multipolar bitufted neurons whose processes branch in
      close proximity to the cell body; bipolar neurons; and multipolar neurons. On day
      23, heavily punctate and asymmetrically labelled cell bodies were dispersed
      throughout the aggregate; neuronal processes were less conspicuous. At 14 and 23
      days, cells expressing glial fibrillary acidic protein (GFAP) and neuronal
      specific enolase (NSE) were abundantly distributed throughout the aggregate.
      Using a double immunoreaction on 14-day-old aggregates revealed that GFAP+ cells
      and their processes were in close apposition to and engulfing the NPY neurons.
      Thus, dissociated fetal NPY neurons undergo morphological differentiation in
      culture along with astrocytes (GFAP+) and other neuronal cell types (NSE+). Based
      on the topographical association of astrocytes and neurons, particularly NPY
      neurons, we propose that the aggregate culture system can serve as a model to
      study the role of paracrine interactions in the regulation of the expression of
      NPY.

PMID- 8275315
TI  - Cholinergic neurons contain Calbindin-D28k in the monkey medial septal nucleus
      and nucleus of the diagonal band: an immunocytochemical study.
AB  - The distribution patterns of choline acetyltransferase (CAT), as a marker for
      cholinergic neurons, and Calbindin-D28k (CaBP) immunoreactivities in the
      forebrain basal ganglia of the Japanese monkey Macaca fuscata were compared.
      Similar distribution patterns of CAT and CaBP immunoreactivities were found in
      the medial septal nucleus (MS) and the nucleus of the diagonal band of Broca
      (DBB). Double-labeling fluorescence immunocytochemistry revealed that most, but
      not all, cholinergic neurons were CaBP-immunoreactive in the MS and DBB. The
      results suggest that CaBP may play a role in the septohippocampal cholinergic
      neuron system of the monkey.

PMID- 8275316
TI  - MK-801-induced symptoms of sensitization. The lack of correlation with the
      extracellular concentration of dopamine in the rat prefrontal cortex.
AB  - It was found that MK-801 evoked signs of behavioral sensitization to its own
      behavioral effects. A second injection of MK-801 (0.4 mg/kg) given 24 h after the
      first one (also 0.4 mg/kg) evoked stronger behavioral effects than the first
      dose. MK-801 (0.4 mg/kg) enhanced the extracellular concentration of dopamine
      (DA) in the prefrontal cortex (PFC). A second dose of MK-801 (0.4 mg/kg) given 24
      h after the first one, evoked a quantitatively similar effect on the
      extracellular concentration of DA. The above results indicate that, at least in
      the PFC, the enhanced behavioral responsiveness to subsequent doses of MK-801 is
      not correlated with alterations in the extracellular concentration of DA.

PMID- 8275317
TI  - Inhibition of nitric oxide formation does not protect murine cortical cell
      cultures from N-methyl-D-aspartate neurotoxicity.
AB  - We examined the role of nitric oxide in N-methyl-D-aspartate (NMDA) receptor
      mediated neurotoxicity in rat and mouse primary cortical cell cultures. In rat
      and mouse cultures, the NO synthase inhibitor, NG-Nitro-L-arginine, blocked cGMP
      formation but not neuronal cell death following a 5-10 min exposure to 300-500
      microM NMDA. NG-Monomethyl-L-arginine was also unable to prevent neuronal death.
      In contrast, the non-competitive NMDA receptor antagonist, dextrorphan, prevented
      both cGMP formation and cell death. While other data suggest that the synthesis
      of nitric oxide can mediate NMDA receptor-mediated neurotoxicity, present results
      suggest that such synthesis is not necessarily required.

PMID- 8275318
TI  - Interleukin-1 beta has excitatory effects on neurons of the bed nucleus of the
      stria terminalis.
AB  - Arginine vasopressin (AVP) is an endogenous antipyretic which acts in the ventral
      septal area (VSA) of the brain following its release from terminals of neurons
      from the bed nucleus of the stria terminalis (BST). The neurochemical mechanisms
      involved in the activation of these BST neurons are unknown. The present study
      was conducted to determine whether a naturally occurring brain cytokine
      (interleukin-1 beta, IL-1) selectively activates the population of BST neurons
      projecting to the VSA or another locus known to receive vasopressinergic input
      from the BST, the habenular nuclei (HAB). Single unit extracellular recordings
      were made from identified BST neurons in urethane-anesthetized rats. Human
      recombinant IL-1 applied iontophoretically or by micropressure, evoked marked
      excitations of long duration in 24% of all BST cells observed (n = 102 cells).
      Iontophoresis of sodium salicylate attenuated or reversed the effects of the
      cytokine in all cases tested. The selective and long-lasting excitatory actions
      of IL-1 on BST neurons are consistent with a direct CNS function for this
      cytokine. In addition, these results are compatible with a role for IL-1 in
      evoking AVP release from BST neurons during fever.

PMID- 8275319
TI  - Interleukin-2 promotes survival and neurite extension of cultured neurons from
      fetal rat brain.
AB  - We investigated the effects of interleukin-2 (IL-2) on the survival and
      morphology of primary cultured neurons from fetal rat brain. Addition of
      recombinant human IL-2 significantly supported the survival of brain neurons in
      high cell density culture, but did not show any effect on the neuronal survival
      in low cell density culture. In addition, IL-2 significantly promoted the neurite
      elongation and branching of hippocampal neurons in low cell density culture.
      These results suggest that IL-2 supports neuronal survival indirectly and
      promotes neuritogenesis by directly acting on brain neurons.

PMID- 8275320
TI  - Locomotor activity in the ischemic gerbil.
AB  - Previous studies have shown that within 24 h after ischemic insult, gerbils
      exhibit an increase in locomotor activity. Because activity gradually diminishes
      to normal levels with repeated testing, it has been argued that this behavior
      represents a reversible or transient effect of ischemia. The present study
      challenged this notion by testing ischemic gerbils at a time when increased
      activity is not observed with repeated testing. Ischemic (5-min bilateral carotid
      occlusion) and sham gerbils were tested for 14 consecutive days after reperfusion
      in an open-field apparatus (n = 6/condition). As previously reported, ischemic
      gerbils exhibited a significant increase in activity (days 1 and 2) which
      returned to control levels with repeated testing (days 13 and 14). A second group
      of ischemic and sham gerbils (n = 6/condition) were tested only on days 13 and 14
      after reperfusion. In contrast to those tested repeatedly, these ischemic gerbils
      displayed increased locomotor activity as compared with sham controls. In
      addition, gerbils in the repeated testing conditions were evaluated in a semi
      novel testing environment on days 15 and 16 after surgery. The locomotor activity
      of ischemic gerbils significantly increased in response to the semi-novel
      environment. These results suggest that the effects of ischemia on locomotor
      activity are not limited to a brief period after occlusion and may represent a
      permanent deficit. In addition, as previously suggested, this behavior may
      represent a deficit in habituation or spatial mapping rather than motor
      hyperactivity.

PMID- 8275321
TI  - Genetically epilepsy-prone rodents show some changes of ion levels in the brain.
AB  - In the present study the water and ion (Na+, K+, Ca2+, Fe3+, Se4+, Mg2+, Mn2+,
      Mn2, Se4+, Cu2+) content in the brain of genetically epilepsy-prone rats (GEPRs)
      and of 21-, 45-, and 60-day-old DBA/2 mice were determined, and compared with
      those measured in normal controls (Sprague-Dawley rats and Swiss mice), to verify
      whether the predisposition to audiogenic seizures (AGS) may be partially related
      to changes in the cerebral osmotic and ionic state. Our findings clearly
      evidenziate two points: a) a more complex shift in brain ionic balance (rather
      than a peculiar modification in the concentration of a single ion) seems very
      likely involved in AGS susceptibility; (b) brain Ca2+ and Se4+ amounts, together
      with the water content, appear to be really important factors to which a role in
      abnormal seizure predisposition may be attributed.

PMID- 8275322
TI  - A motor-driven miniature multiple microelectrode manipulator for recording from
      the cortical neuropile of the awake monkey in operant behavior paradigms.
AB  - An improved version of the Blum and Feldman multiple microelectrode manipulator
      is described. The main innovation is a design based on miniaturization and light
      weight (75 g), which allows head mounting with minimal disturbance to the animal
      in awake monkey operant behavior studies. The major features of the previously
      described model are preserved: simultaneous independent manipulation of four
      microelectrodes, in order to record from at least four single units, that may be
      crosscorrelated. With the new design better adjustment of intermicroelectrode
      distances for studies of interneural distances of 300 microns to 7 mm, and an
      easier automatic, computer-controlled monitoring of distances transversed into
      the brain are possible.

PMID- 8275323
TI  - Opioid receptor-dependent long-term potentiation at the lateral perforant path
      CA3 synapse in rat hippocampus.
AB  - The involvement of opioid receptors in the induction of long-term potentiation
      (LTP) was investigated in the lateral and medial perforant path projections to
      area CA3 of the hippocampus in anesthetized rats. The opioid receptor antagonist
      naloxone (10 nmol), applied to the hippocampal CA3 region 10 min prior to
      tetanization, blocked the induction lateral perforant path-CA3 LTP induced by
      high-frequency stimulation. By contrast, LTP induction in medial perforant path
      CA3 was not attenuated by a 10 nmol quantity of naloxone. (+)-Naloxone (10 nmol),
      the inactive stereoisomer of naloxone, was without effect on the induction of
      lateral perforant path-CA3 LTP. Naloxone applied 1 h following LTP induction did
      not reverse established lateral perforant path-CA3 LTP, indicating that opioid
      receptors are involved in the induction but not the maintenance of LTP in this
      pathway. LTP of medial perforant path responses developed immediately, while LTP
      of lateral perforant path responses was slow to develop. The latter pattern is
      similar to the time course of the development of LTP observed at the mossy fiber
      CA3 synapse and suggests that lateral and medial perforant path synapses may use
      distinct mechanisms of both induction and expression of LTP. These data extend
      previous findings demonstrating opioid receptor-dependent mechanisms of LTP
      induction at both the mossy fiber-CA3 synapse and the lateral perforant path
      dentate gyrus synapse. We suggest that lateral perforant path and mossy fiber
      synapses may utilize similar, opioid receptor-dependent, mechanisms of LTP
      induction and expression.

PMID- 8275324
TI  - Behavioral and electrophysiological aspects of nitrous oxide dependence.
AB  - We examined the effect of 70% nitrous oxide (N2O) on locomotion and visual-evoked
      potentials (VEP) in rats. The animals exposed to N2O showed an initial decrease
      of locomotion, followed by development of tolerance and unaltered motor activity
      during N2O withdrawal. Similarly, an initial decrease of VEP amplitudes was
      followed by tolerance to N2O. In addition, some amplitudes (N2-P3, P3-N3, and N3
      P4) exceeded the control values, indicating an increase of neuronal excitability
      of the visual system during a long lasting exposure to N2O. The increase of VEP
      amplitudes was further potentiated by cessation of this gas. The VEP latencies
      after initial increase, returned to normal and remained unaltered during N2O
      withdrawal suggesting that the speed of neurotransmission is not essentially
      changed during chronic exposure to N2O. However, a significant increase of
      neuronal excitability during chronic N2O exposure, which further increased by
      cessation of N2O, could be of clinical importance. Therefore, monitoring of VEP,
      particularly the amplitude values, may significantly improve a detection of
      altered neuronal excitability during anaesthesia and drug withdrawal.

PMID- 8275325
TI  - Hypothalamic stimulation induces vagally mediated hypocalcemia in the rat.
AB  - To elucidate hypothalamic involvement in blood calcium homeostasis, the effects
      of unilateral electrical stimulation (0.1 mA, 0.5 ms, 30 Hz, 60 min) of the
      lateral hypothalamic area (LHA), the paraventricular nucleus (PVN), and the
      ventromedial nucleus of the hypothalamus (VMH) on the blood concentration of
      ionized calcium were examined in the anesthetized rats. LHA stimulation induced a
      sustained decrease (0.05-0.07 mM fall) in the blood calcium level during the
      period of 60 to 150 min (end of the measurements) after stimulation. In contrast,
      PVN stimulation elicited a transient hypocalcemia (0.07 mM decrease) 60 min after
      stimulation. The hypocalcemic effects of LHA and PVN stimulation were eliminated
      by vagotomy of the gastric branches and the thyroid/parathyroid branches,
      respectively. VMH stimulation, using the same parameters, did not induce any
      significant change in blood calcium. The results suggest that the LHA and the PVN
      have a hypocalcemic function that is mediated, at least in part, by the vagus
      nerve innervating the stomach and the thyroid/parathyroid glands, respectively.

PMID- 8275326
TI  - Visual and vestibular projections to tongue motoneurons.
AB  - The rabbit hypoglossal neurons, localized in the mediocaudal part of the XIIth
      nucleus, receive visual and vestibular inputs able to induce reflex responses
      functionally driven both to prepare the oral cavity for food reception and to
      ensure a correct postural arrangement of the tongue. The aim of the present
      research was to show a possible convergence of visual input on the hypoglossal
      neurons modulated by the vestibular system and, thus, demonstrate that visual
      input plays a part in the control of the tongue posture. It was found that 78% of
      tested neurons responded to both photic stimulation of the retinae, performed by
      a conventional strobe unit, and electrical stimulation of the labyrinth, with
      different patterns of response. Moreover, visual input significantly modified
      both the hypoglossal neuron response and the electromyographic genioglossal
      response to caloric stimulation of the labyrinth. Because a significant visual
      influence on the hypoglossal nucleus response and the genioglossal muscle
      response to labyrinthine stimulation was observed, it can be concluded that
      vision does integrate the spatial information of the labyrinth to modulate the
      postural tone of the tongue muscles.

PMID- 8275327
TI  - Effects of systemic clonidine on auditory event-related potentials in squirrel
      monkeys.
AB  - Event-related potential (ERP), electroencephalographic (EEG), and behavioral data
      were collected from squirrel monkeys (Saimiri sciureus) in a 90-10 auditory
      oddball paradigm. Background or target tones were presented once every 2 s, and
      responses to the targets were rewarded. ERPs were recorded from epidural
      electrodes following systemic administration of clonidine (0.1 mg/kg) or a saline
      placebo. EEG power spectral and behavioral performance were assessed
      simultaneously as indices of behavioral state. Clonidine significantly decreased
      the area and increased the latency of a P300-like potential. The amplitude and
      areas of the earlier P1, N1, and P2 components and a later slow wave-like
      potential were not reduced, nor were ther latencies altered. Clonidine produced
      increased EEG power in the alpha range (7.5-12 Hz) and decreased power in the
      upper beta range (20-40 Hz) but did not affect performance in the oddball task.
      Because two major effects of clonidine are to substantially reduce activity in
      the noradrenergic nucleus locus coeruleus (LC) and to reduce norepinephrine (NE)
      release from axons, the present results support the hypothesis that the LC and
      its efferent projection system are important in modulating the activity of P300
      like potentials.

PMID- 8275328
TI  - Long-term adrenalectomy reduces hippocampal granule cell excitability in vivo.
AB  - Ten days after bilateral adrenalectomy (ADX), neural transmission between the
      perforant path and hippocampal dentate granule cells was severely impaired in the
      anaesthetized rat, in that the slope of the stimulus-response curve was reduced
      to less than half the value in sham controls, the stimulation current necessary
      to elicit a standard population spike (PS) field potential was increased
      approximately threefold, the amplitude of PS and its ratio to the slope of the
      field excitatory postsynaptic potential (EPSP) were reduced, and high-frequency
      tetanization (TET) of the perforant path resulted in potentiated PS with smaller
      amplitude and higher onset latency in ADX rats than in sham controls. However,
      the fractional increase of PS amplitude and its decay following TET were similar
      in 10 day-ADX and sham groups, from which it is inferred that long-term ADX
      entails a general decrease of dentate granule cell excitability, particularly at
      somatic membrane level, without specifically affecting the mechanism of long-term
      potentiation. None of the above changes occurred 24 h after ADX.

PMID- 8275329
TI  - Determination of the structural requirements for the inhibitory action of gastrin
      releasing peptide on growth hormone release.
AB  - We have previously determined that gastrin-releasing peptide (GRP) suppresses
      plasma growth hormone (GH) levels and blocks the response to growth hormone
      releasing factor (GRF) following its injection into the third ventricle (3V) of
      conscious male rats. To determine the portion of the peptide required for this
      action, fragments of the peptide were injected at various doses to determine
      their effect on plasma growth hormone and the response to a test dose of GRF (1
      microgram/kg IV). The GRP 1-16 lowered plasma GH and blocked the response to GRF
      following an intraventricular injection of 2 micrograms but not 0.2 microgram of
      the peptide. Carboxy-terminal fragments were more effective. AcGRP20-27 was
      partially effective at a 100 times lower dose of 2.0 ng, a result similar to that
      obtained with the related peptide, bombesin. Even the C-terminal heptapeptide
      AcGRP-27 was effective at a dose of 2 ng. The results indicate that the C
      terminal heptapeptide is the minimal requirement for intraventricularly injected
      GRP to suppress plasma GH levels and block the response to GRF.

PMID- 8275330
TI  - Efficacy of a putative GABA analog on synaptic transmission in the cat spinal
      cord.
AB  - 4-Hydroxy-4-phenylcaproamide (HPhCA), at high doses or rates of IV injection
      depressed the ventral root reflexes elicited by nerve or dorsal root stimulation.
      The D (direct) and I (synaptic) ventral root waves and the antidromic (A) dorsal
      root wave evoked by intraspinal stimulation were also depressed. Similar effects
      were produced when HPhCA was applied topically on the cord dorsum. At 80 mg/kg
      and 8 mg/kg/min, the spinal reflexes and the I wave were facilitated for 4 to 6
      h, but the D and A waves were depressed. Intracellular recordings from
      motoneurons showed that HPhCA injection produced: hyperpolarization that lasted
      several hours, short lasting (< 20 min) facilitation of both EPSPs and IPSPs as
      well as spike-like potentials (SLPs) that were triggered by EPSPs even though the
      neuron was hyperpolarized. SLPs may reach the threshold for full spikes. Our
      results suggest that the spinal depression results from hyperpolarization of
      motoneurons and the initial facilitation appears to be presynaptic. The late
      facilitation may be produced by SLPs. HPhCA does not appear to mimic the actions
      of GABA in primary afferents fibers and motoneurons.

PMID- 8275331
TI  - Fibers immunoreactive for nerve growth factor receptor in adult rat cortex and
      hippocampus mimic the innervation pattern of AChE-positive fibers.
AB  - Numerous reports have indicated that nerve growth factor (NGF) exerts
      neurotrophic effects on the cholinergic neurons of the basal forebrain. Receptors
      for NGF (NGFR) have been demonstrated on cholinergic perikarya in the medial
      septum, diagonal band of Broca, and basal nucleus of Meynert. These neurons
      provide the major cholinergic innervation to the cerebral cortex and hippocampus,
      and previous studies have shown that their terminal plexuses also possess NGFR.
      However, these studies have shown only isolated examples of immunoreactive
      fibers. In the present paper we confirm and extend the observation of the
      presence of NGFR immunoreactivity in the hippocampus and cortex of adult rat by
      showing the entire plexus and demonstrating that the plexus is strikingly similar
      to the pattern of cholinergic innervation. Fibers stained for
      acetylcholinesterase (AChE) and NGFR immunoreactivity were found in all layers of
      the parietal cortex. Within the hippocampus, fibers were observed in all regions,
      but were most dense in the strata oriens, pyramidale, and radiatum of hippocampal
      subfields CA1 and CA3. Particularly intense staining was found throughout the
      dentate gyrus. Partial transections of the fimbria-fornix, which disrupt fibers
      projecting from the medial septum to the hippocampus, concomitantly abolish the
      innervation pattern of both NGFR and AChE. These results provide additional
      evidence that NGFR are associated with septohippocampal and basocortical
      cholinergic fibers.

PMID- 8275332
TI  - Chemoarchitectonics of axonal and perikaryal acetylcholinesterase along
      information processing systems of the human cerebral cortex.
AB  - The distribution of axonal and perikaryal acetylcholinesterase (AChE) was studied
      in whole-brain sections. All cytoarchitectonic sectors and cortical layers of the
      human cerebral cortex contained AChE-rich axons. These axons displayed multiple
      varicosities which appeared to come in contact with AChE-rich and AChE-poor
      cortical perikarya. The upper layers of cortex tended to contain the highest
      density of AChE-rich axons. The AChE-rich axons were more dense in limbic
      paralimbic areas of cortex than in primary sensory-motor and association areas.
      Within unimodal sensory association areas, the parasensory (upstream) sectors had
      a slightly lesser density of AChE-rich axons than the downstream sectors. Within
      paralimbic areas, the nonisocortical sectors displayed a distinctly higher
      density of AChE-rich axons than the more differentiated isocortical sectors.
      These observations indicate that the distribution of AChE-rich axons displays
      orderly variations that obey the organization of information processing systems
      in the cerebral cortex.

PMID- 8275333
TI  - Differential distribution of tau proteins in developing cat cerebellum.
AB  - The differential distribution and phosphorylation of tau proteins in cat
      cerebellum was studied with two well characterized antibodies, TAU-1 and TAU-2.
      TAU-1 detects tau proteins in axons, and the epitope in perikarya and dendrites
      is masked by phosphorylation. TAU-2 detects a phosphorylation-independent epitope
      on tau proteins. The molecular composition of tau proteins in the range of 45 kD
      to 64 kD at birth changed after the first postnatal month to a set of several
      adult variants of higher molecular weights in the range of 59 kD to 95 kD. The
      appearance of tau proteins in subsets of axons corresponds to the axonal
      maturation of cerebellar local-circuit neurons in granular and molecular layers
      and confirms previous studies. Tau proteins were also identified in synapses by
      immunofluorescent double-staining with synapsin I, located in the pinceau around
      the Purkinje cells, and in glomeruli. Dephosphorylation of juvenile cerebellar
      tissue by alkaline phosphatase indicated indirectly the presence of
      differentially phosphorylated tau forms mainly in juvenile ages. Additional TAU-1
      immunoreactivity was unmasked in numerous perikarya and dendrites of stellate
      cells, and in cell bodies of granule cells. Purkinje cell bodies were stained
      transiently at juvenile ages. During postnatal development, the intensity of the
      phosphate-dependent staining decreased, suggesting that phosphorylation of tau
      proteins in perikarya and dendrites may be essential for early steps in neuronal
      morphogenesis during cat cerebellum development.

PMID- 8275334
TI  - Ontogenic development of brain asymmetry in dopaminergic neurons.
AB  - In the present study the right-left brain asymmetry of central dopamine (DA)
      systems during postnatal brain development is evaluated. DA and
      dihydroxyphenylacetic acid (DOPAC) levels increased from neonatal to adult life
      in both the forebrain and mesencephalon. This increase was not similar in the
      right and left brain sides. From neonatal life to adulthood a fall was observed
      in (a) DA percentage in the DA high-brain side in the mesencephalon and (b) DOPAC
      percentage in the DOPAC high-brain side in both the forebrain and mesencephalon.
      The percentage of lateralized rats (more than 65% of DA or DOPAC levels in either
      brain side) also decreased during ontogeny. Thus, biochemical lateralization
      decreases during ontogeny. The right-left brain correlation for DA level and DA
      turnover was used to evaluate the inter-hemispheric regulation of dopaminergic
      systems. The correlation coefficient was near to 0 during postnatal life and
      around -0.8 during adulthood in both forebrain and mesencephalon. Taken together,
      these data suggest that the ontogenic decrease of in brain asymmetry for DA or
      DOPAC levels is related to the postnatal development of an inter-hemispheric
      regulatory system that control dopaminergic neurons activity.

PMID- 8275335
TI  - Cold water swimming stress alters NGF and low-affinity NGF receptor distribution
      in developing rat brain.
AB  - We have previously shown that the nerve growth factor (NGF) is released into the
      bloodstream following intraspecific fighting behaviour and that the level
      released correlates with the number of fighting episodes. We subsequently
      reported that NGF and its messenger RNA are present in identified hypothalamic
      nuclei and increase following intermale fighting behaviour. This report provides
      data showing that in 16-day-old rats cold water swimming stress (CWSS) alters the
      distribution of low-affinity NGF-Receptors (p75NGFR) and NGF levels in the
      central nervous system. A significant increase of NGF level was observed in the
      cortex, while the p75NGFR immunoreactivity decreased in neurons of the septum,
      nucleus basalis and striatum. Choline acetyltransferase activity in forebrain
      tissues remained at baseline levels. Our result suggests that NGF and p75NGFR,
      involved in the development and differentiation of the nervous system, are
      affected by stress.

PMID- 8275336
TI  - Prenatal cocaine eliminates the sex-dependent differences in activation observed
      in adult rats after cocaine challenge.
AB  - In the adult rat, acute administration of cocaine results in enhanced expression
      of certain behaviors. This activation is often referred to as "stereotypy"
      because of its repetitive nature. Repeated exposure to the same dose of cocaine
      does not result in tolerance or a dimunition of these behavioral responses.
      Rather, an increased responsiveness to cocaine, termed "sensitization," is
      observed. Female rats, in comparison to male rats, display greater activation to
      a given dose of cocaine and greater sensitization with repeated exposure. As
      prenatal cocaine exposure can involve repeated exposure to the drug, we examined
      the behavioral activation induced by an acute dose of cocaine. Young adult rats
      of both sexes received a challenge dose of cocaine to determine the long-term
      effects of repeated in utero exposure to cocaine (30 mg/kg daily, SC) given
      between gestational days 8-20. As expected, female offspring of dams exposed to
      saline in utero displayed greater activation to a 20 mg/kg SC dosage of cocaine
      than their male counterparts. However, these sex differences were completely
      eliminated by prenatal exposure to cocaine. That is, female rats receiving
      cocaine during the prenatal period showed no more activation to an acute dose of
      cocaine as young adults than either control males or those males receiving
      cocaine in utero. Males exposed in utero to cocaine showed activation to cocaine
      challenge equivalent to that displayed by males exposed to saline in utero.
      Prenatal exposure to cocaine may alter sexual differentiation of the brain.

PMID- 8275337
TI  - Characterization of high voltage spindles and spatial memory in young, mature and
      aged rats.
AB  - EEG was recorded from rats of three age groups, and high voltage spindles (HVS)
      were measured during waking immobility. Total mean spindling times in 4- (young),
      10- (mature) and 22- (aged) month-old rats were 0.3 +/- 0.1, 20.4 +/- 7.4 and
      33.4 +/- 14.9 s, respectively. Spatial memory was assessed in these rats using a
      discrimination version of the Morris water maze. Performance (as measured by
      number of choice errors) was compared with the extent of HVS activity by
      characterizing rats as "spindling" if the total average duration of HVS
      discharges exceeded 5 s, and "non-spindling" if these discharges averaged less
      than 5 s. Spindling and nonspindling rats had similar performance during
      training; however, on a 14-day retention trial, spindling rats had a
      significantly higher mean error score of 2.8 +/- 0.5 compared with 1.2 +/- 0.3
      for nonspindling rats (p = 0.011). These results show that spindling activity
      increases in mature and aged rats, and that HVS discharges may be an
      electrophysiological change that parallels the progression of brain dysfunction
      associated with memory impairment.

PMID- 8275338
TI  - Habituation and generalization of phobic responses to cat odor.
AB  - Rats exposed to a cloth impregnated with the odor of a cat made fewer contacts
      with the cloth and spent more time sheltering under the food and water hopper
      than did rats exposed to a neutral odor. In two experiments there was little
      evidence of between-trial habituation of these responses to cat odor. The pattern
      of within-session changes depended on the trial duration (15 or 60 min) and the
      initial level of the avoidance responses. In order to test for conditioned
      generalization of the avoidance responses to the test situation, rats with two
      previous exposures to cat odor were given a third trial in which they were
      exposed to a neural odor. Experiment 1 showed that those previously exposed to
      cat odor for two 15 min trials spent more time sheltering when exposed to the
      neutral odor cloth than those previously exposed to the neutral odor. Experiment
      2 confirmed this effect and found that the increase in sheltering was even more
      marked for a group exposed to cat odor for 60 min on trial 1. The number of
      contacts with the neutral odor cloth on trial 3 was reduced only in the group of
      high avoiders (defined as making no contacts with the cat odor cloth in the first
      5 min of trial 1). Thus, both the duration of exposure to cat odor and the
      initial response level were important in determining the conditioned
      generalization of the responses to a phobic stimulus.

PMID- 8275339
TI  - Cocaine exposure during pregnancy affects rat neonate and maternal brain
      glycosphingolipids.
AB  - Behavioral dysfunctions in offspring exposed in utero to cocaine have been
      observed, along with alterations in dopamine systems, but few studies of the
      underlying biochemistry have been conducted. Because of their documented roles in
      neuronal maturation, glycosphingolipids were analyzed in whole brains of
      offspring exposed gestationally to cocaine. Rat offspring exposed to cocaine in
      utero exhibited markedly elevated levels of both total gangliosides (p < 0.001)
      and neutral glycosphingolipids (p < 0.01) at postnatal day 1. However, by
      postnatal day 11 levels of gangliosides and neutral glycosphingolipids returned
      to control values. These effects were not restricted to chronic cocaine exposure
      early in life, in that ganglioside content of whole maternal brains was also
      elevated (p < 0.001), though less than that observed with the neonate brains.
      Qualitatively, no differences in ganglioside nor neutral glycolipid structure
      distribution were observed between cocaine-exposed and normal animals following
      separation by HPTLC and HPLC. These elevations are in contrast to those following
      alcohol exposure, where decreases in brain gangliosides have been observed.
      Neurochemical consequences of prenatal exposure to cocaine may be far-reaching
      and may not be restricted to the dopamine system.

PMID- 8275340
TI  - Involvement of the serotonergic system in the hypoactive and antinociceptive
      effects of nicotine in mice.
AB  - Pretreatment with the 5-HT2 antagonist ketanserin and the 5-HT1A/2 antagonist
      spiperone did not reduce nicotine-induced hypomotility in mice, nor did MDL 7222,
      a selective 5-HT3 antagonist. In addition, 8-OH-DPAT and buspirone, 5-HT1A
      agonists, had no significant effects on nicotine-induced hypomotility. However, 8
      OH-DPAT and buspirone did reduce the antinociceptive effects of nicotine in a
      dose-dependent manner. 8-OH-DPAT blockade of this nicotine effect was reversed by
      spiperone, a 5-HT1A/2 antagonist. Nicotine's ED50 was increased from 1.00 mg/kg
      (0.90-1.68) to 2.00 mg/kg (1.6-2.55) and 2.66 (1.7-3.51) by buspirone and 8-OH
      DPAT, respectively. Ketanserin, spiperone and MDL 7222 had no significant effect
      on nicotine-induced antinociception. The present data suggest an important role
      of 5-HT1A receptors in the modulation of antinociceptive actions of nicotine.

PMID- 8275341
TI  - Dihydrotestosterone-sensitive neurons in the male rat ventromedial hypothalamus.
AB  - Electrical stimulation of the midbrain central gray caused antidromic activation
      in 273 neurons in and around the hypothalamic ventromedial nucleus in 40 urethan
      anesthetized male rats. The latency (range: 2-39 ms) and threshold (100-1,600
      microA) of the responses were compared among intact males and orchidectomized
      males, which received either no treatment, daily injections of testosterone
      propionate or dihydrotestosterone, or a combined estradiol benzoate and
      progesterone injection. Recordings were from comparable neuronal pools, because
      probability distribution for the latency as well as histological localization of
      each response were not different among groups. Orchidectomy decreased the mean
      threshold, and either treatment reversed the effect. Dihydrotestosterone
      increased the mean threshold by reducing the number of cells with thresholds
      below 600 microA, to a level as in intact males. Estrogen reduced the number of
      cells responding at 300-900 microA, but at lower thresholds, fell short of
      replicating the distribution in intact males. Testosterone reinstated the
      distribution as in intact males. It was concluded that different subgroups of
      ventromedial hypothalamic neurons with specific sensitivity to metabolites of
      testosterone project to the central gray.

PMID- 8275342
TI  - Systemic signals contribute to induced morphological changes in the hypothalmo
      neurohypophysial system.
AB  - A systemic injection of hypertonic saline causes morphological changes in the
      supraoptic nucleus (SON) of the hypothalamus and the posterior pituitary,
      including withdrawal of astrocytic glial processes from among magnocellular
      neuroendocrine cells (MNCs) in the SON and increases in neural apposition with
      the basal lamina (BL) in the posterior pituitary. This study investigated whether
      systemic adrenalin provides a signal for these changes. Three groups of rats were
      given intraperitoneal injections of hypertonic (1.5 M) or normal (0.15 M) NaCl
      and were sacrificed 5 h after injection. One group was given no additional
      treatment, one group was anesthetized from prior to injection through perfusion,
      and one group was bilaterally adrenal-medullectomized several days prior to
      injections. Morphometric analysis of electron micrographs revealed rats given 1.5
      M NaCl with no additional treatment showed expected changes in the SON and
      pituitary. Rats given 1.5 M NaCl and anesthetized showed diminished responses in
      the SON, and no changes in the pituitary compared to anesthetized rats given 0.15
      M NaCl. No changes in withdrawal of glial processes from among MNCs or in neural
      apposition with the BL were seen in medullectomized animals. Thus, both
      anesthesia and adrenal-medullectomy interfere with signals for glial retraction
      and suggest that these responses are mediated by adrenalin.

PMID- 8275343
TI  - Prenatal cocaine exposure: increased striatal dopamine transporter binding in
      offspring at 3 and 6 months of age.
AB  - Prior studies indicate that prenatal cocaine exposure can alter dopamine
      transporter binding in mature mice. To determine the persistence of these
      effects, pregnant mice were treated with cocaine, 10 mg/kg/d, during days 13 to
      20 of gestation and dopamine transporter binding was evaluated in offspring at 3
      and 6 months of age. In contrast to prior studies, binding in striatum was
      significantly increased at both time points in cocaine-exposed mice compared to
      controls.

PMID- 8275344
TI  - Localization of dipole by boundary element method in three dimensional
      reconstructed monkey brain.
AB  - The boundary element method was applied to 3-dimensionally reconstructed monkey
      brain to localize a current source generator (dipole) of somatosensory evoked
      potentials (SEPs) recorded from epidural electrodes under assumption that a brain
      is electrically homogeneous and is bounded by a high resistant substance (skull).
      Absolute mean deviation of estimated dipoles from actual dipoles artificially
      generated by electrical stimulation at known coordinates in the brain were within
      1-3 mm. The estimated dipole computed from SEPs by right median nerve stimulation
      at latency of P10-N10 waves was located in area 3b of the somatosensory hand area
      in monkey. Our data suggest that this technique of locating dipoles by the
      boundary element method applied to a reconstructed brain allows accurate
      determination of the 3-dimensional coordinates of a dipole.

PMID- 8275345
TI  - Dipole tracing of monkey somatosensory evoked potentials.
AB  - Current source generators (dipoles) of somatosensory evoked potentials (SEPs) in
      response to electrical stimulation of the median nerve in anesthetized monkeys
      were localized by the dipole tracing method (DT) which can approximate surface
      potential distributions to an equivalent dipole. The locations and latencies of
      dipoles estimated by DT were confirmed by recording multiple unit activities from
      the parietal cortices of the same monkeys investigated by DT. Loci of generators
      for each SEP component were: P10 and N10, area 3b; P12, areas 1 and 2; P18, area
      5. The results indicate that DT could trace the successive movement of generators
      of SEPs from the primary somatosensory area to area 5, which has been suggested
      in neuroanatomical studies to be part of the hierarchical sequence of
      somatosensory processes.

PMID- 8275346
TI  - Opioid antagonist-induced receptor upregulation: effects of concurrent agonist
      administration.
AB  - The present study examined whether opioid antagonist-induced receptor
      upregulation could be antagonized by simultaneous treatment with opioid agonists.
      Mice were treated concurrently with opioid agonists (morphine, fentanyl,
      etorphine) and antagonists (naloxone, naltrexone) over a period of 7-8 days.
      Concurrent morphine (1 or 4, 75 mg SC implanted pellets), fentanyl (5.0
      mg/kg/day, infusion) or etorphine (0.25 mg/kg/day, infusion) administration were
      unable to inhibit upregulation of mu opioid (DAMGO) receptors by either naloxone
      (1 mg/kg/day, infusion) or naltrexone (15 mg or 2 mg SC implanted pellet). Only a
      very high infusion dose of etorphine (10 mg/kg/day) inhibited upregulation by
      naltrexone (2mg SC implanted pellet). These results indicate that antagonist
      induced upregulation is a robust, receptor-mediated phenomenon.

PMID- 8275347
TI  - Dental complications of Paget's disease: the need for hard facts about hard
      tissues.

PMID- 8275348
TI  - Site of bone density measurement may affect therapy decision.
AB  - The purpose of this study was to determine whether bone mineral density (BMD)
      measurements at the lumbar spine and femoral neck provided comparable information
      to women planning to use that knowledge to help them make a decision about
      hormone replacement therapy. Eighty-eight healthy Caucasian women, aged 44-59 and
      within 0 to 5 years of menopause, participated in the study. BMD measurements
      were performed at the lumbar spine (L1-L4) and the femoral neck by dual energy X
      ray absorptiometry (DXA). Criteria suggested by the National Osteoporosis
      Foundation were used to categorize women as "at risk" for osteoporosis, bone
      density more than one standard deviation (SD) below the young adult mean, or as
      "low risk", bone density at or above this level. The results indicated that 46
      women would be classified into the low risk category on the basis of spinal BMD
      alone. However, 28 of these 46 women would fall into the at risk category when
      the femoral neck BMD was measured. Sixty-one percent of women informed they were
      at low risk on the basis of spinal BMD would be considered at risk based on
      femoral neck BMD. When femoral neck BMD was used as the primary risk indicator,
      14% of the women classified as low risk would be at risk if spinal BMD were
      added. These results suggest that both lumbar spine and proximal femur
      measurements should be made when women are using bone density measurements as an
      aid in deciding whether or not to use hormone therapy in their postmenopausal
      years.

PMID- 8275349
TI  - Individuals who sustain nonosteoporotic fractures continue to also sustain
      fragility fractures.
AB  - This retrospective case control study was done in order to investigate whether
      patients who sustain a "nonosteoporotic fracture" early in life also continue to
      sustain fragility fractures later in life. All patients who had been treated at
      the Department of Orthopedics in Malmo with a tibial shaft fracture from 1949 to
      1963 (n = 767) or an ankle fracture from 1961 to 1965 (n = 786) were included in
      this study. At the time of follow-up in 1992, 231 of the patients who sustained a
      tibial shaft fracture and 260 of the patients who sustained an ankle fracture
      were still living in the city of Malmo. Objective registration was done of all
      subsequent fractures that these former patients had sustained. Comparison was
      done with corresponding data from double numbers of age- and sex-matched controls
      who at that time (1950s and 1960s) had no such fractures. At the time of the
      fracture as well as today, the controls were living in the area of Malmo.
      Individuals with earlier tibial or ankle fractures had an increased incidence of
      fractures generally classified as fragility fractures. There was no difference in
      this respect between men and women, nor whether the initial fracture had been
      diaphyseal or metaphyseal. We conclude that sustenance of fractures early in life
      may serve as a predictor for fragility fractures later in life.

PMID- 8275350
TI  - Acute effects of nasal salmon calcitonin on calcium and bone metabolism.
AB  - Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium
      metabolism and biochemical markers of bone turnover were investigated in 12
      healthy male volunteers in a randomized, placebo-controlled, cross-over design.
      The nasal spray was given in the morning, and subsequently blood and urine
      samples were collected for 26 hours. There was a significant decrease in serum
      ionized calcium with a nadir 4 hours after administration of nasal SCT
      accompanied by a significant increase in serum parathyroid hormone (P = 0.01) and
      serum calcitriol (P = 0.04). Nasal SCT did not reduce urinary
      hydroxyproline/creatinine. Urinary deoxypyridinoline/creatinine was lowered
      significantly 2 hours after administration of nasal SCT and throughout the first
      24 hours, but remained unchanged for the last 2 hours. On a 24-hour basis,
      urinary deoxypyridinoline/creatinine decreased from 14.1 (3.5) nmol/mmol to 11.7
      (3.2) nmol/mmol after nasal SCT (P = 0.04). Nasal SCT did not change the serum
      levels of alkaline phosphatase, osteocalcin, and the carboxyterminal propeptide
      of type 1 procollagen. The results indicate that nasal SCT given as a single dose
      provokes a modest decrease in bone resorption lasting several hours, but leaves
      bone formation unaffected.

PMID- 8275351
TI  - Pamidronate is effective for Paget's disease of bone refractory to conventional
      therapy.
AB  - Paget's disease of bone is characterized by primary osteoclastic dysfunction and
      prolonged treatment with conventional medications including calcitonin and
      etidronate, results in a number of patients becoming refractory to treatment. We
      have evaluated the effectiveness of three dosage regimes of
      aminohydroxypropylidene bisphosphonate (pamidronate) in 15 patients with
      extensive Paget's disease who had become refractory to conventional therapy. Nine
      patients had pamidronate (intravenous infusion of 30 mg over 4-5 hours at monthly
      intervals) for 6 months. A further four patients received 30 mg of pamidronate
      infusion daily for 6 consecutive days and another two patients, 60 mg on 3
      consecutive days (total dose of 180 mg/patient). In all three groups the bone
      specific alkaline phosphatase and urinary hydroxyproline excretion both fell by
      75% (P < 0.001). All but one patient showed a marked improvement in clinical
      symptomatology (pain and mobility) and biochemical parameters indicating
      decreased bone turnover. Remissions achieved (> 12 months) with all three
      regimens were comparable. The pagetic bone pain was reduced and the mobility was
      significantly improved after 3 months of therapy and was continued for up to 1
      year. Currently, it may be difficult to justify the use of intravenous
      bisphosphonate as the first line of therapy for Paget's disease, but it does seem
      to have a definite place in patients with severe Paget's disease who do not
      respond to other therapeutic agents. Here we demonstrate that pamidronate is
      highly effective in patients with extensive Paget's disease who became refractory
      to conventional treatment. Further studies are necessary to optimize the dosage
      and frequency of administration of pamidronate.

PMID- 8275353
TI  - Epitaxial overgrowth of apatite crystals on the thin-ribbon precursor at early
      stages of porcine enamel mineralization.
AB  - The aim of the present work was to investigate changes in cross-sectional
      morphologies of enamel crystallites as a function of location in secretory
      porcine enamel. Enamel tissues were obtained from 5- to 6-month-old slaughtered
      piglets. For examination by electron microscopy, a portion of the secretory
      enamel was embedded in resin and ultrathin sections were prepared with a diamond
      knife. In parallel studies, compositional and structural changes of enamel
      mineral were assessed by chemical analysis and Fourier transform infrared (FTIR)
      spectroscopy. For this purpose, two consecutive layers of the outer secretory
      enamel, each approximately 30 microns thick, were separated from the labial side
      of permanent incisors. Using high-resolution electron microscopy, early events of
      enamel crystal growth were characterized as the epitaxial growth of small apatite
      units on the lateral surfaces of the initially precipitated thin ribbon. These
      apatite units had regular triangle or trapezoid cross-sections. After fusions of
      those isolated trapezoids on both lateral sides of the platy template, the
      resulting enamel crystallites had the well-documented flattened-hexagonal shapes
      in cross-sections. The initially precipitated thin plate was buried inside the
      overgrown apatite lamella and then retained as a central dark line. Similar
      morphological evidence for the epitaxial nucleation and overgrowth of
      carbonatoapatite on the platy template was obtained in vitro. Chemical and FTIR
      analyses of the enamel layer samples showed that the characteristics of the
      youngest enamel mineral were distinct from those of enamel crystals found in
      older secretory enamel.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275352
TI  - The effect of warfarin on urine calcium oxalate crystal growth inhibition and
      urinary excretion of calcium and nephrocalcin.
AB  - Urine contains inhibitors of calcium oxalate (CaOx) crystal growth. One such
      inhibitor is nephrocalcin (NC), a glycoprotein which is made in the kidney and
      contains several residues of gamma-carboxyglutamic acid (Gla) per molecule. The
      presence of Gla may be important to its ability to inhibit crystal growth.
      Several studies suggest that vitamin K-dependent proteins may also play a role in
      renal calcium (Ca) handling, and that vitamin D deficiency may lead to excess
      urinary Ca loss, but the effect of the vitamin K antagonist warfarin on urinary
      Ca excretion and CaOx growth inhibition in humans is not known. We studied 11 men
      while they were taking warfarin for a mean of 252 days, and again a mean of 64
      days after its discontinuation. Urinary Ca excretion did not differ between those
      on or off warfarin, or between those on warfarin and normal controls. The ability
      of the subjects' urine to inhibit CaOx crystal growth did not differ on or off
      warfarin, or from that of control urine, and the excretion of immunoreactive NC
      also did not differ between these groups. NC was found to be responsible for
      approximately 16% of the CaOx growth inhibition seen. These results do not
      suggest that vitamin K-dependent proteins play a major role in renal Ca excretion
      in men, or that interference with vitamin K alters NC excretion or inhibitory
      activity of the urine.

PMID- 8275354
TI  - Enamelins in the newly formed bovine enamel.
AB  - The possibility of using the antisera raised in rabbits against the porcine 25
      kDa amelogenin, 32 and 89 kDa enamelins, and the 13-17 kDa nonamelogenin for the
      differentiation and identification of the protein components in bovine immature
      enamel was examined. Although the immunoreactivities of these antisera against
      bovine enamel proteins were weaker than those against the porcine proteins, it
      was found that these antisera could differentiate and demonstrate
      immunohistochemically a characteristic distribution of three different kinds of
      enamel protein components in the bovine secretory stage enamel similar to those
      observed in the porcine immature enamel. Of the several high molecular weight
      proteins being reactive to the anti-porcine 32 and 89 kDa enamelin sera, the 130
      kDa protein, having the highest molecular weight, was extracted and purified from
      the bovine enamel sample which was obtained by peeling approximately 30-microns
      thickness of the outermost layer of the secretory stage enamel. The amino acid
      composition of the 130 kDa protein was similar to the known bovine enamelins, and
      was rich in aspartic acid, glutamic acid, proline, and glycine. The results could
      suggest that the enamelins of lower molecular weight than this protein, which are
      found in the bovine secretory stage enamel, are derived from this precursor
      protein.

PMID- 8275355
TI  - Temporal changes during bone regeneration in the calvarium induced by osteogenin.
AB  - Repair of rat craniotomy defects, 8 mm in diameter, was compared with that of
      defects treated with either rat insoluble collagenous bone matrix (ICBM) or
      partially purified bovine osteogenin, a bone-inductive protein, reconstituted
      with ICBM (OG/ICBM). Repair of all defects was similar histologically throughout
      the first 3 days, characterized by acute, then chronic inflammation and
      granulation tissue formation. In defects treated with OG/ICBM, cartilage and
      osteoblasts were present at day 5. By day 9, cartilage and osteoid production
      were active. New bone showed hematopoietic tissue by day 11; a complete bone
      bridge was established by day 21. By day 42, fatty marrow was present. Defects
      treated with ICBM alone showed islands of cartilage and bone embedded in
      connective tissue at day 9, which reached peak maturity by day 14. In these and
      in untreated defects, significant osteoblastic and osteoclastic activity, located
      primarily at the margins of the defects, subsided by day 28. Untreated defects
      gradually filed in with fibrous connective tissue which matured throughout 156
      days. Radiopacity, quantified by computerized image analysis, increased
      significantly between days 9 and 11 in OG/ICBM-treated defects, and remained
      greater (P < 0.05) than that of the ICBM-treated defects. There was a more
      gradual increase in radiopacity in ICBM-treated defects. The sequence of
      morphologic events during calvarial bone regeneration was very similar to that
      described previously for heterotopic bone formation induced by demineralized bone
      matrix.

PMID- 8275356
TI  - Mechanical properties, bone mineral content, and bone composition (collagen,
      osteocalcin, IGF-I) of the rat femur: influence of ovariectomy and nandrolone
      decanoate (anabolic steroid) treatment.
AB  - Nandrolone decanoate (ND) is an anabolic steroid with a positive effect on bone
      mass in osteoporotic patients. The mechanism of action, (i.e., reduction of bone
      resorption and/or stimulation of bone formation), the ultimate effect on
      mechanical properties, and the most effective dosage are not yet clear. To
      address these issues, dose-related effects of the long-term effect of ND on serum
      and bone biochemistry, bone mineral content, and bone mechanical properties in
      ovariectomized (OVX) rats (12 weeks old at the start of the experiment) were
      studied for 6 months. The results were compared with those obtained in age
      matched, intact, and OVX rats. OVX caused in the femur a significant increase in
      net periosteal bone formation and net endosteal bone resorption of bone collagen
      content and torsional strength, and of serum alkaline phosphatase, osteocalcin,
      and insulin-like growth factor-I (IGF-I) levels, whereas cortical bone density
      and calcium/creatinine and phosphorus/creatinine in 24-hour urine were
      significantly reduced. Treatment of OVX rats with 1 mg ND/14 days resulted in a
      significant increase in periosteal bone formation, femur length, cortical and
      trabecular bone mineral content and density, torsion stiffness and strength, and
      bone IGF-I content, and a decrease in serum osteocalcin, urinary
      calcium/creatinine levels, and bone collagen content compared with OVX controls.
      The higher ND dosage of 2.5 mg/14 days did not improve the results. ND treatment
      did not reverse all changes induced by OVS to the level of the intact controls.
      These results indicate that ND acts as an antiresorptive drug and as a home
      formation stimulating drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275357
TI  - The effects of the aminobisphosphonate alendronate on thyroid hormone-induced
      osteopenia in rats.
AB  - Hyperthyroidism, either endogenous or iatrogenic, leads to increased bone
      turnover and osteopenia. This study was conducted to examine (1) whether thyroid
      hormone excess in rats causes bone changes similar to those seen in patients with
      hyperthyroidism, and (2) the effects of the aminobisphosphonate alendronate on
      the thyroid hormone-induced bone changes. Sprague-Dawley male rats, divided into
      four groups, received L-thyroxine (T4) 250 micrograms/kg/day (+T4) or vehicle (
      T4) subcutaneously six times per week and alendronate 1.75 mg/kg (+ALN) or
      vehicle (-ALN) orally twice a week. Rats were sacrificed after 3 weeks of
      treatment, blood samples were analyzed for serum T4, triiodo-L-thyronine (T3),
      and osteocalcin, and the proximal tibiae were processed for histomorphometric
      analysis. Serum T4 and T3 levels measured 20-24 hours after the last injection
      were 2 to 2.5-fold higher in +T4 groups than in -T4 groups. Serum osteocalcin was
      significantly (P < 0.05) higher in +T4/-ALN group than in the other groups, which
      were not statistically different from each other. T4 treatment (+T4/-ALN)
      significantly decreased the amount of cancellous bone volume (-45%) and increased
      osteoid surface (+254%), osteoblast surface (+111%), and osteoclast surface
      (+176%) relative to control values. Alendronate increased the bone volume above
      control values in both T4-treated (+T4/+ALN) and untreated (-T4/+ALN) rats, and
      prevented the T4-induced increase in bone turnover in +T4/+ALN rats. It is
      concluded that (1) excess thyroid hormone induces cancellous bone loss associated
      with high bone turnover in the rat, and (2) this bone loss can be prevented by
      alendronate through the inhibition of osteoclastic activity.

PMID- 8275358
TI  - Continuous alendronate treatment throughout growth, maturation, and aging in the
      rat results in increases in bone mass and mechanical properties.
AB  - Alendronate (4-amino-1-hydroxybutylidene bisphosphonate) is a novel amino
      bisphosphonate that is being developed for the treatment of osteolytic bone
      disorders such as osteoporosis. As part of a 2-year carcinogenicity study, we
      investigated the morphologic and biomechanical effects of long-term alendronate
      (ALN) therapy, given throughout skeletal growth, maturation, and aging, on rat
      vertebrae and femora. Three treatment groups, receiving either deionized water,
      low- (1.00 mg/kg), or high-dose (3.75 mg/kg) ALN, were given daily oral treatment
      for 105 weeks. Results from mechanical tests indicate that ALN therapy (in males)
      increased the vertebral ultimate compressive load by 96% in the high- and 51% in
      the low-dose groups when compared with controls. ALN similarly increased the male
      ultimate femoral bending load by 59% in the high- and 31% in the low-dose groups.
      Vertebrae and femora from female rats treated with both high- and low-dose ALN
      also failed at significantly higher loads than controls, but no differences were
      seen between low- and high-dose groups. Morphologic analysis of both male and
      female vertebrae revealed a dose-dependent increase in area fraction of bone.
      Rats receiving high-dose ALN had a greater area fraction of bone than those
      receiving low doses. Both groups were greater than controls. Thus, the
      administration of ALN resulted in increased femoral cortical bending load when
      compared with control animals, as well as increased vertebral ultimate
      compressive load commensurate with a dose-related preservation of vertebral
      bone.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275359
TI  - On fluoride and bone strength.

PMID- 8275360
TI  - Aging and bone quality: an underexplored frontier.

PMID- 8275361
TI  - NIA workshop on aging and bone quality. Bethesda, September 3-4, 1992.
      Proceedings.

PMID- 8275362
TI  - Osteocytes, strain detection, bone modeling and remodeling.
AB  - One of the characteristic features of mammalian and avian bone is a population of
      live cells of the osteoblast lineage distributed both on the surface and
      throughout the matrix. These cells communicate with one another via gap
      junctions. A number of roles have been proposed for both osteocytes and the
      lacunar/canalicular labyrinth they occupy. These include arrest of fatigue
      cracks, mineral exchange, osteocytic osteolysis, renewed remodeling activity
      after release by resorption, stimulation, and guidance of osteoclastic cutting
      cones involved in mineral exchange and the repair of microdamage, strain
      detection, and the control of mechanically related bone modeling/remodeling. The
      question of whether osteocytes control or influence modeling and remodeling is of
      major importance. Such influence could be crucial in relation to three importance
      consequences of remodeling activity: calcium regulation, microdamage repair, and
      mechanically adaptive control of bone architecture. Mechanically adaptive control
      of bone architecture requires feedback concerning the relationship between
      current loading and existing architecture. This feedback is most probably derived
      from the strain in the matrix. The arrangement of the osteocyte network seems
      ideally suited to both perceive strain throughout the matrix and to influence
      adaptive modeling and remodeling in a strain-related manner. The hypothesis that
      osteocytes perform this role has growing experimental support.

PMID- 8275363
TI  - Bone remodeling in hip fracture.
AB  - Hip fracture incidence has shown strong upward secular trends in many societies
      with wide differences in age adjusted incidence between nations. Falls and
      reduced physical activity have emerged as the strongest risk factors in
      epidemiological studies, while clinical investigations have pointed to secondary
      hyperparathyroidism as an important candidate cause of the loss of femoral
      cortical bone in old age. Until recently there have been few studies performed
      directly on the region of interest in the proximal femur. Non-invasive
      methodology using 85Sr has now been developed by our group for measuring bone
      formation and (with concurrent serial DXA densitometry) resorption in the femoral
      neck. Bone turnover averaged about 8% annually in controls. A group of younger
      cases of femoral fracture showed similar indices of total and regional bone
      formation to a control group; but their resorption was higher. To further
      investigate this, a femoral neck bone biopsy technique has been developed which
      can be applied to fracture cases treated by arthroplasty. Preliminary studies
      have established that the anatomical asymmetry of the neck in cross-section is
      considerable and imposes restraints on the interpretation of smaller or
      incomplete femur biopsies. Prospects are quite good that, in the absence of
      tetracycline pre-labeling, mineralization can be studied by assessment of
      alkaline phosphatase-positive surfaces in cryostat sections. Moreover, such
      sections will permit study of other anatomically localized metabolic activities
      as well as antigen expression and osteocyte viability. Candidate mechanisms for
      the regional decline in bone quality as well as bone mass in subjects suffering
      hip fracture can now be investigated more effectively.

PMID- 8275364
TI  - Osteocyte death and hip fracture.
AB  - The viability of osteocytes can be demonstrated in sawn decalcified sections of
      bone by their lactate dehydrogenase activity. In the cancellous bone of the
      femoral head, the proportion of lacunae containing viable osteocytes decreased
      from 88 +/- 7% (mean +/- SD) at 10-29 years to 58 +/- 12% (P < 0.001) by 70-89
      years. Viability in the second lumbar vertebra was 88 +/- 3% in subjects aged 25
      90 years and did not decrease with age. Mean osteocyte viability in the femoral
      head of 21 hip fracture patients aged 72-94 years was 58 +/- 21%, similar to
      controls of a similar age, though there was greater variation and, in five
      patients, osteocyte viability was less than 25%. In hip fracture patients,
      microfracture callus incidence correlated positively with osteocyte viability,
      with little or no fracture callus observed if the bone viability was low.
      Ultimate compressive strength did not correlate with osteocyte viability. In the
      femoral head there is gradual, age-related reduction in osteocyte viability that
      can be more pronounced in hip fracture. Osteocyte death may affect bone quality
      by impairing repair of fatigue damage.

PMID- 8275365
TI  - Vertebral structure and strength in vivo and in vitro.
AB  - The incidence of vertebral fragility fractures has increased 2-4-fold during the
      past 30 years and the rate of increase is the same for both men and women. To
      arrest or reverse this increase, thorough understanding of normal, age-related
      changes in bone structure and strength is crucial. The human vertebral body is
      constructed to provide maximum strength with minimum bone mass. The strength is
      the sum of bone size, cortical thickness, trabecular architecture, and bone mass.
      With age, all these factors change due to the remodeling process, but the decline
      in bone strength is much more pronounced than the decline in mass. In individuals
      with very low bone mass, this discrepancy between mass and strength is even more
      marked. Structural studies have all shown a disruption of the trabecular network
      with age--mainly caused by perforation of horizontal supporting struts. These
      changes begin in the vertebral center. Later, a decline in cortical thickness is
      disclosed. The biomechanical consequence of this is a 4-6-fold decrease in
      vertebral strength during normal aging. As the structural changes cannot be
      reversed, it is difficult to increase bone strength by therapeutic regimens.
      Focus should therefore be placed on prevention. Three avenues are suggested: (1)
      to use the vast amount of existing biological data in a computer model to
      increase the understanding of the relationship among bone structure, mass, and
      strength, and to help identify the intervention regimens offering the best
      prospects of success; (2) to investigate characteristics of load-bearing
      trabecular bone that does not fracture; and (3) to focus more on life-style
      factors.

PMID- 8275366
TI  - Measurement and significance of three-dimensional architecture to the mechanical
      integrity of trabecular bone.
AB  - The mechanical properties of trabecular bone have been shown to vary
      significantly with age, anatomic location, and metabolic condition. Efforts
      towards predicting its behavior have been extensive, and significant relationship
      between measures of density and mechanical integrity have been reported.
      Unfortunately, the significant heterogeneity in trabecular bone anisotropy
      contributes to significant unexplained variance in its strength and modulus when
      predicted using scalar measures of mass or density. As a result, numerous
      investigators have attempted to include measures of architecture in an effort to
      more rigorously investigate potential physiologic optimization strategies, as
      well as account for the increased fragility associated with advancing age. In our
      laboratories we have utilized a unique three-dimensional, microcomputed
      tomography system to measure trabecular plate thickness, trabecular plate
      separation, trabecular plate number, surface to volume ratio, bone volume
      fraction, anisotropy, and connectivity in isolated specimens of trabecular bone.
      The results of these studies demonstrate that in normal bone, more than 80% of
      the variance in its mechanical behavior can be explained by measures of density
      and orientation. The independent measures of connectivity and trabecular plate
      number were found to be significantly correlated with bone volume fraction,
      suggesting a potential strategy in the formation of trabecular bone. It might be
      hypothesized, however, that the relationship between bone volume fraction and
      connectivity may be substantially altered under conditions associated with aging,
      fragility, or metabolic bone disease. This hypothesis would be consistent with
      the histologic evidence of reduced connectivity in osteopenic patients.

PMID- 8275367
TI  - Bone mass and beyond: risk factors for fractures.
AB  - Numerous prospective studies have demonstrated a strong relationship between bone
      mass and fracture risk. The fact that the bone mass distributions of fracture and
      nonfracture cases overlap does not necessarily indicate a shortcoming of bone
      mass, but might instead be due to the sporadic nature of falls and the influence
      of other fracture risk factors. The recent finding that prevalent fractures are
      strong predictors of fracture risk, independent of bone mass, suggests (but does
      not prove) that there may be other, potentially measurable fracture risk factors
      that complement, and act independently of, bone mass. This paper reviews possible
      mechanisms by which prevalent fractures might serve as etiologic risk factors, or
      as surrogate indicators of other risk factors. Potential risk factors other than
      bone mass and prevalent fractures are also considered. Whether or not etiologic
      fracture risk factors other than bone mass can be identified, it appears that
      treatments that influence bone will be most effective if begun early, before bone
      strength becomes impaired and fractures begin to occur.

PMID- 8275368
TI  - Architecture and vertebral fracture.
AB  - Bone strength is determined by mass density, structural arrangement, and the
      presence of microdamage. This presentation focuses on trabecular microstructure
      as an element of bone strength, particularly in the syndrome of vertebral
      compression fracture. The base material comes from transilial biopsies from 90
      patients with the crush fracture syndrome and from 34 normal volunteers who
      underwent transilial biopsy. Trabecular connectivity was compared in these two
      groups. Patients and normals were then matched for trabecular bone volume
      (BV/TV). To highlight measures of trabecular connectivity, three general methods
      for examining trabecular connectivity were applied to the 23 patient-control
      pairs matched for BV/TV. The conventional method of Parfitt showed that
      trabecular number was decreased by 11%, trabecular separation was increased by
      9%, and trabecular thickness was increased by 9% in patients compared with
      controls. The method of counting trabecular nodes and trabecular free ends showed
      that in the patients, free ends were decreased by 37% and nodes were decreased by
      37%. The marrow space star volume (the average volume of marrow measured from
      radii placed at random points within the marrow and extending to trabecular
      surface) was 36% greater in the patients. All three methods are measures of
      trabecular connectivity (the density of connections between trabeculae). All
      three demonstrated less trabecular connectivity in the patients versus controls
      for identical BV/TV. Patients with vertebral fractures had fewer trabecular
      elements rather than global thinning of trabeculae. Differences in measures or
      connectivity were not accompanied by significant differences in any of the
      measures of bone remodeling dynamics, as examined by tetracycline
      labels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275369
TI  - Role of trabecular morphology in the etiology of age-related vertebral fractures.
AB  - Osteoporotic compression fractures of the spine differ from most other age
      related fractures in that they usually are associated with minimal trauma and
      with loads no greater than those encountered during normal activities of daily
      living. With aging and osteoporosis, there is progressive resorption of bone,
      resulting in reductions in bone density, thinning of trabeculae, and loss of
      trabecular contiguity. These changes in trabecular bone structure are associated
      with losses in bone strength which are disproportionate to the reductions in bone
      mass alone. To explain this disproportionate loss of bone strength, the
      prevailing opinion is that density reductions in the vertebral centrum are
      accompanied by a reduction in the number of trabeculae, by preferential
      resorption of horizontal trabeculae, and by hypertrophy of the remaining vertical
      trabeculae. To evaluate this view of vertebral morphology, we performed three
      dimensional stereological analysis of trabecular bone extracted from midsagittal
      sections of first lumbar vertebral bodies from 12 donors spanning an age of 27-81
      years. We found that both the number (R2 = 0.63, P < 0.01) and thickness (R2 =
      0.91, P < 0.01) of trabeculae decreased linearly with density (as expressed by
      bone volume fraction) whereas the spacing between the trabeculae (R2 = 0.61, P <
      0.01) increased reciprocally. There were more vertical trabeculae with transverse
      trabeculae at all densities, and the number of vertical trabeculae changed with
      density at twice the rate of the number of transverse trabeculae (P < 0.001).
      These data do not support the prevailing view that there is preferential
      resorption of horizontal trabeculae or hypertrophy of the remaining vertical
      trabeculae.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275370
TI  - Trabecular microfracture.
AB  - Healing trabecular microfractures are a common feature in cancellous bone. These
      lesions, when observed in macerated cancellous bone slices, measure about 500
      microns in diameter and surround fractures in trabeculae with microcallus.
      Whether microcallus is a structure acting primarily as a transient brace,
      preventing relative movement of the fragmented segments and enabling the
      trabecula to heal, or whether it is a permanent buttress reducing the stress on
      the fractured strut, preventing the healing process, is not known. Microfractures
      are the result of normal physical activity. Hence, the widespread occurrence of
      trabecular microfracture in cancellous bone implies that a reasonable rate of
      microfracture is physiologically tolerable. There are three putative effects for
      trabecular microfracture. One is that, in response to impulse loading, cancellous
      subchondral bone increases its rigidity due to osteosclerosis resulting from bone
      formed around microfractures. Another hypothesis is that, if sufficient
      trabecular microfractures occur, they will compromise the trabecular structure of
      the vertebra and the proximal femur leading to osteoporotic fracture. By inducing
      remodeling changes, microfractures have an effect on the maintenance of joint
      structure. There are two histological patterns for microfractures: an early
      stage, when actively forming woven bone is bridging the fracture; and a more
      common late stage, when woven bone is inactive. Femoral studies fail to
      demonstrate that an increasing number of healed or healing microfractures in
      osteoarthrosis causes the increase of bone in the head of femur. Only one study
      has reported a significant increase in the number of trabecular microfractures in
      osteoarthritic femoral heads compared with normal controls. This significant
      increase was in patients taking antiinflammatory drugs.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8275371
TI  - Clinical determination of bone quality: is ultrasound an answer?
AB  - Progress in clinical characterization of bone relies on developing a means to
      clinically assess all of the important determinants of bone quality,
      specifically, the intrinsic material properties of a bone (stiffness and
      brittleness) versus the macroscopic structural properties [apparent mass density
      (g/cc), structural shape and distribution of cortical mass, trabecular
      architecture, extent of unrepaired microdamage, and defects associated with the
      accelerated remodeling in early menopause]. Ultrasound devices currently measure
      parameters related to either of only two basic properties: bone ultrasound
      attenuation (BUA) or the apparent velocity of wave propagation (AVU). Theory and
      repeated corroboration in the laboratory have shown that the velocity of sound in
      solids such as bone has a quantitative relationship to the elastic modulus (or
      stiffness) and mass density. Although no comparable physical model exists for
      BUA, growing in vitro and in vivo empirical evidence shows a relationship to
      stiffness and mass density as well. Therefore, the question of ultrasound's
      ability to provide additional, clinically useful information about bone quality
      reduces to this: Does bone quality depend significantly on bone stiffness and
      does stiffness depend on factors other than bone mass alone? Clinical study
      results provide mounting evidence of ultrasound's abilities. (1) Numerous studies
      compare either velocity or BUA with BMC or BMD. The correlation coefficients vary
      widely between studies, even when repeated by the same investigators and
      laboratories. Two studies demonstrated this by comparing groups of subjects who
      are indistinguishable by BMD at the lumbar spine, but whose mean AVU readings are
      significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275372
TI  - Ultrasound study of bone in vitro.
AB  - Ultrasound has been investigated as a tool for characterizing the biomechanical
      competence of bone. The rationale for using ultrasound rests on two points.
      First, its interaction with tissues can be used to measure their density,
      velocity, and structure, and thus to characterize the elasticity and to infer the
      strength of bone. Second, ultrasound may be used to characterize tissue
      properties over a wide range of spatial dimensions and organizational levels,
      ranging from its constituents (e.g., trabeculae for cancellous bone) to the
      entire organ. Different ultrasound techniques can be used to investigate diverse
      bone properties, but two techniques have emerged as having the potential for
      providing useful information on problems of current biomedical interest. These
      measure two parameters, density and velocity, which correlate with the elastic
      and ultimate properties of bone. In particular, the elasticity E is formally
      related to the product of density and velocity squared, E = rho v2. Moreover, it
      has been shown by mechanical testing that there is a single linear correlation
      between elasticity and strength at all orientations, both in cortical and in
      cancellous bone, materials with a strong intrinsic anisotropy. At the tissue
      level, it may therefore be expected that the ultrasound parameters will prove to
      be useful predictors of bone strength and of its dependence on orientation. In
      vitro ultrasound studies have shown that these properties can be measured
      specifically and quantitatively, and that they vary under different physiological
      conditions.

PMID- 8275373
TI  - Potential role of nuclear magnetic resonance for the evaluation of trabecular
      bone quality.
AB  - This paper discusses two novel applications of nuclear magnetic resonance (NMR)
      as an investigational tool for the assessment of cancellous bone
      microarchitecture. It further outlines extensions of the method for in vivo
      clinical evaluation of bone strength in patients with skeletal disorders such as
      osteoporosis. The first method relies on the hypothesis that the presence of two
      phases of different magnetic permeability, i.e., bone and bone marrow, causes a
      spatial nonuniformity of the magnetic field across the measurement volume. The
      resulting spread in resonance frequency shortens the decay time constant (T2*) of
      the time domain proton signal in bone marrow or its substitute (water). Increased
      trabecular spacing, such as it occurs in osteoporosis, reduces the spatial field
      inhomogeneity and thus prolongs T2*, which has been shown both in vitro and in
      vivo. Subjects with osteoporosis, characterized by either low bone mineral
      density and/or spine compression fractures, have T2* values that are
      significantly prolonged. The second method focuses on a direct measurement of
      micromorphometric parameters of cancellous bone, using the principles of proton
      NMR microscopy in conjunction with computer processing of the resulting digital
      images. Image contrast between the trabeculae and the intertrabecular space is
      based on the marrow protons providing a signal, as opposed to bone, which appears
      with background intensity. Once tissues have been classified (into bone and
      marrow), for example, by means of a histogram-based segmentation algorithm, bone
      area fraction, mean trabecular plate density (MTPD), and mean trabecular plate
      thickness (MTPT) can be computed without the need for further operator
      intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275374
TI  - The assessment of vertebral bone macroarchitecture with X-ray computed
      tomography.
AB  - On a macroscopic scale, the structural characteristics of whole bone are likely
      dependent on the distribution of typically applied loads to the bone surface, the
      full bone shape, the thickness of the cortex at the various surface positions,
      and the distribution of cancellous bone material. X-ray computed tomography is
      presently the best available method for assessing the macroarchitecture of bone
      in-vivo. Fine detail, three-dimensional CT methods are available to measure
      regional bone mineral density (rBMD) in contiguously spaced small volumes and
      have been applied to the assessment of macroarchitecture in vertebrae. The more
      detailed rBMD methods produce radiation exposures to the subject similar to
      lumbar radiography and substantially higher than traditional QCT. The cancellous
      bone within lumbar vertebral bodies has been found in cross-sectional studies to
      have increased density in the inferior, posterior and lateral regions. Notably,
      regions with higher density at age 40 have a larger decline with age. The
      vertebral body cortex declines with age at a slower rate than observed for
      cancellous bone; however, the decline with age of cortical bone appears to vary
      substantially amongst subjects. The amount of cortical bone in the anterior
      portion of the body is less than in the lateral portion, which may explain
      previous discrepancies in assessing the fraction of vertebral body bone in the
      cortex.

PMID- 8275375
TI  - The epidemiology of fragility fractures: is there a role for bone quality?
AB  - Fragility fractures, particularly those of the hip, vertebrae, and distal
      forearm, constitute a major public health problem. The two ultimate determinants
      of fracture are bone strength and propensity to trauma. Bone strength depends not
      only upon bone mass but also upon a variety of qualitative aspects of bone
      structure. These include its architecture, the amount of fatigue damage it has
      sustained, and changes in its bulk material properties, indices that are
      collectively subsumed into the term "bone quality." Fragility fractures show
      differences in their patterns of incidence by age, sex, ethnic group, geographic
      area, and season. Many of these differences are currently unexplained, and
      disorders of bone quality might contribute to them. There are two fracture sites
      at which evidence implicates bone quality more directly--the spine and proximal
      femur. Many vertebral compression fractures follow minimal trauma, and controlled
      studies suggest that vertebral microarchitecture contributes to fracture risk
      independently of vertebral bone mass. At the hip, observational studies have
      pointed to a role for disordered trabecular architecture, accumulation of
      microfractures (fatigue damage), and the accumulation of osteoid. The extent to
      which these phenomena act independently of bone mass, however, remains uncertain.

PMID- 8275376
TI  - Bone quality: a determinant for certain risk factors for bone fragility.
AB  - Low bone quantity alone is insufficient cause for fragility fractures. This paper
      examines the role of bone quality in the fracture risk associated with age, sex,
      and race. Aspects of bone quality to be considered are bone architecture, matrix,
      mineralization, and fatigue damage. The trabecular network becomes progressively
      disconnected and weaker with age. Death of old osteocytes leads to
      hypermineralization and brittleness of bone. The stability of bone collagen
      declines with age, and unremodeled bone accumulates fatigue damage. The lower
      bone fragility rates in males than in females may be due to a combination of the
      larger male skeleton, greater cortical bone density after age 60 years, and
      greater bone turnover which would replace fatigue damaged bone. Fragility
      fracture rates in American and African blacks are lower than in whites, bone
      mineral density (BMD) is greater in American but not in African blacks (except
      for hip BMD), and American blacks have lower and African blacks higher bone
      turnover compared to whites. In South African blacks, trabeculae are thicker and
      better connected and trabecular bone undergoes less destructive age changes than
      in whites. To reconcile the disparate findings in American and African blacks we
      suggest that both groups have a genetic tendency to greater BMD than whites;
      American blacks realize this potential and African blacks do not, possibly
      because of calcium deficiency. Consequent high turnover removes fatigue damage
      and so improves bone quality. Weight-bearing activity in African blacks may be
      responsible for good hip bone density and thick trabeculae.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8275377
TI  - Is there a role for bone quality in fragility fractures?

PMID- 8275378
TI  - Aging and strength of bone as a structural material.
AB  - There is a general, age-related reduction in the material strength and stiffness
      of bone in both men and women. Between the ages of 35 and 70, cortical bone
      strength in bending is diminished by about 15-20%, and cancellous bone strength
      in compression is reduced about 50%. In addition, bone becomes increasingly
      brittle and fractures with less energy. It is hypothesized that this tendency is
      driven by the need for remodeling to repair fatigue damage, and the fact that
      most osteonal and endotrabecular remodeling events fail to replace all the bone
      that they remove. Each remodeling event also introduces cement line interfaces,
      which although affording protection against fatigue failure, weaken bone for
      monotonic loading. Remodeling also affects collagen fiber orientation,
      mineralization, and the amount of unrepaired fatigue damage, which are additional
      determinants of bone strength and stiffness. Mechanical factors apparently
      inhibit age-related bone loss where stresses are higher by reducing remodeling
      rates and/or the deficit at each remodeling site. They may also stimulate
      modeling responses, primarily in the form of periosteal bone formation, which, in
      men more than women, alter bone size and shape to effectively compensate for loss
      of material strength. Suggested directions for future research include
      elucidation of the relationships between (1) histologically observable
      microcracks and bone fragility, (2) remodeling and the repair of fatigue damage,
      and (3) estrogen and other hormones and mechanically adaptive responses.

PMID- 8275379
TI  - Age-related changes in female femoral neck geometry: implications for bone
      strength.
AB  - Bone strength is a function of both bone mass and its geometric distribution, a
      factor that is obscured in the conventional bone mineral analysis. Structural
      geometry is particularly important in areas such as the femoral neck that are
      exposed to bending loads in vivo. Here we present results of a study examining
      age changes in the structural geometry of the female femoral neck derived from
      dual photon absorptiometry (DPA) data. In a previous study, differences in the
      aging patterns of males and females over the entire adult age range were
      demonstrated. In that study, only males showed "compensatory" geometric
      restructuring of the femoral neck which tended to offset loss of bone mineral
      with age. In the present study, femoral neck structural properties from 1044
      women were examined for aging trends before and after the approximate age of
      menopause (50 years). Women in the premenopausal age range showed a 4% decline
      per decade in femoral neck BMD, but no change in the femoral neck cross-sectional
      moment of inertia (CSMI). This aging pattern is similar to that of males in our
      earlier study, and in both cases resulted in little or no increase in femoral
      neck bending stresses. After age 50, however, women show a more rapid decline in
      femoral neck BMD (7% per decade) accompanied by a decline in CSMI of 5% per
      decade. These changes result in increases in femoral neck stresses of 4-12% per
      decade due to the apparent lack of compensatory restructuring to offset the loss
      of bone mineral.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275380
TI  - A new theory of bone lamellation.
AB  - A comparative polarized light (PLM), scanning (SEM), and transmission (TEM)
      electron microscopy study was carried out on cross- and longitudinal sections of
      human lamellar bone in the tibiae of four male subjects aged 9, 23, 45, and 70
      years. SEM analysis was also performed on rectangular-prismatic samples in order
      to observe each lamella sectioned both transversely and longitudinally. The
      results obtained do not confirm the model hitherto suggested to explain the
      lamellar appearance of bone. In particular, the classic description by Gebhardt
      (still accepted by the majority of bone researchers), which suggests that
      collagen fibers alternate between longitudinal and transversal in successive
      lamellae, or that they have spiral paths of different pitches, appears to be no
      longer acceptable in the light of our findings. In fact, SEM and TEM observations
      here reported agree in demonstrating that lamellar bone is made up of alternating
      collagen-rich (dense lamellae) and collagen-poor (loose lamellae) layers, all
      having an interwoven arrangement of fibers. No interlamellar cementing substance
      was observed between the lamellae, and collagen bundles form a continuum
      throughout lamellar bone. Preliminary measurements of lamellar thickness indicate
      that dense lamellae are significantly (P < 0.001) thinner than loose lamellae.
      Compared with the classic model of Gebhardt, the dense lamellae correspond to the
      transverse lamellae and are birifringent under PLM, whereas the loose lamellae
      correspond to the longitudinal lamellae and are extinguished. Collagen-fiber
      organization in dense and loose lamellae is discussed in terms of bone
      biomechanics and osteogenesis.

PMID- 8275381
TI  - Age and disease-related changes in the mineral of bone.
AB  - Bone mineralization changes with age and disease. The distribution of mineral
      particles in a given bone (mineralization profile) has been studied using density
      fractionation as well as microradiography and electron backscattering imaging.
      The biological determinant of mineralization is the rate of turnover. During
      rapid growth and periods of high remodeling, mineralization is shifted towards
      lower mineral density (hypomineralization). During aging and periods of low
      remodeling, mineralization is shifted towards higher mineral densities
      (hypermineralization). Chemicals can also influence the mineralization profile of
      bone. Fluoride induces hypermineralization by stabilizing the apatite lattice and
      reducing bone mineral solubility, whereas strontium induces hypomineralization by
      loosening the apatite lattice and increasing bone mineral solubility. Drugs such
      as bisphosphonates induce hypermineralization by inhibiting resorption and acting
      as crystal poison. Finally, mineralization can be impaired by defects as in
      rickets and osteomalacia or made excessive by continuous accretion of mineral
      without resorption as in osteopetrosis.

PMID- 8275382
TI  - Safety factors in bone strength.
AB  - Functional in vivo strain data are examined in relation to bone material
      properties in an attempt to evaluate the relative importance of osteoporotic bone
      loss versus fatigue damage accumulation as factors underlying clinical bone
      fragility. Specifically, does the skeleton have a sufficiently large safety
      factor (ratio of bone failure strain to maximum functional strain) to require
      that fatigue damage accumulation is the main factor contributing to increased
      risk of fracture in the elderly? Existing methods limit in vivo strain
      measurements to the surfaces of cortical bone. Peak principal compressive strains
      measured at cortical sites during strenuous activity in various mammalian and
      avian species range from -1700 to -5200 mu epsilon, averaging -2500 mu epsilon (
      0.0025 strain). Much of this threefold variation reflects differences in the
      intensity of physical activity, as well as differences among species and bones
      that have been studied. Peak strains can also vary as much as tenfold at
      different cortical sites within the same bone. No data exist for cortical bone
      strain during strenuous activity in humans, but it is likely that human bones
      experience a similar range of peak strain levels. Compact bone fails in
      longitudinal compression at strains as high as -14,000 to -21,000 mu epsilon, but
      begins to yield at strains between -6000 and -8000 mu epsilon. Given that
      yielding involves rapid accumulation of microdamage within the bone, it seems
      prudent to base skeletal safety factors on the yield strain, rather than the
      ultimate failure strain of bone tissue. Safety factors to yield failure therefore
      range from 1.4 to 4.1.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275384
TI  - Remodeling and the repair of fatigue damage.
AB  - This paper reviews the direct and indirect evidence for and against the idea that
      bone remodeling repairs fatigue damage. It defines experiments that should be
      performed to determine whether the accumulation and repair of fatigue damage is
      relevant to the pathogenesis of osteoporotic fracture. The experimental evidence
      favors the hypothesis that microdamage evokes local remodeling. The data suggest
      that the balance between the microdamage burden and bone repair is nearly
      constant. The indirect evidence comes from clinical observations that show
      positive relationships between depressed bone formation rate or prolonged
      remodeling period with bone fracture. More compelling indirect evidence comes
      from studies in which bone remodeling was pharmaceutically depressed, and
      fracture incidence rose in direct proportion. Data on microdamage accumulation
      were not collected in these studies. Conversely, some experimental evidence
      disputes a direct relationship between fatigue microdamage and repair. In these
      studies, increased amounts of bone microdamage in hyperadrenocortical dogs, and
      in irradiated dogs, could not be demonstrated even though bone fragility
      increased without associated osteopenia. Finally, the indirect evidence that
      argues that microdamage does not initiate repair is based on inference and does
      not provide an adequate test of the hypothesis. In balance, the current body of
      evidence favors the contention that bone remodeling repairs fatigue damage and
      thereby prevents fracture. Future studies should verify that microdamage
      accumulates when bone fracture occurs in conjunction with depressed remodeling
      activation frequency.

PMID- 8275383
TI  - When bone mass fails to predict bone failure.
AB  - New technology for noninvasive measurement of bone mass has enabled many studies
      of bone mass and its relationship to fracture, which challenge the view that bone
      mass is the only relevant factor in the etiology of fractures. Several studies
      have reported ROC curves that generally show values of about 80%. No convincing
      evidence suggests that one technique is superior to another. The reported
      relative risks or odds ratios for a fracture usually range between 1.2 and 2.5
      per SD. There is no doubt that the risk of a fracture increases as the bone
      density decreases. However, even with a low bone mass, the risk of not fracturing
      a bone over the next year is over 90%. Most of the data suggest that patients
      with severe vertebral fractures have lower bone mass than those with mild
      fractures, but some women with similarly low bone mass have mild or no fractures.
      The weight of the evidence suggests that age has an effect on fracture incidence
      which is independent of bone mass. Trauma is such a major factor that it is
      surprising to find almost no studies that have controlled for it. The
      relationship between bone mass and bone failure is strong, but other factors must
      also be contributing to the bone failure which, like heart failure or renal
      failure, is a complex, multifactorial disease.

PMID- 8275385
TI  - Bone age, mineral density, and fatigue damage.
AB  - The most plausible purpose for bone remodeling is to prevent excessive aging of
      bone, which can cause osteocyte death and increase susceptibility to fatigue
      microdamage. The age of any particular volume of bone depends on two factors: the
      probability of remodeling beginning on the nearest bone surface, which is given
      by the local activation frequency; and the probability of a particular remodeling
      event penetrating to a specified distance from the surface. These two
      probabilities can be combined in a mathematical model. According to the model,
      within about 40 microns from the surface, the rate of surface remodeling is the
      main determinant of bone age, but beyond 40 microns, the distance from the
      surface becomes progressively more important. Beyond 75 microns, the bone is
      essentially isolated from surface remodeling. Application of the model to
      subjects with and without vertebral fracture indicated that the proportion of
      iliac cancellous bone with a mean age greater than 20 years was less than 20% in
      all the control subjects without fracture, but was more than 20% in about one
      third of the patients with fracture. Bone age is a major determinant of the
      degree of mineralization, so that osteoporotic patients with prolonged bone age
      should have bone of higher true mineral density. Accordingly, mineral density
      distribution was determined by scanning electron microscopy with backscattered
      electron imaging, calibrated in terms of atomic number.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8275386
TI  - Systemic and local factors and the maintenance of bone quality.
AB  - Bone formation, an essential process for the maintenance of bone mass and
      strength, depends on changes in osteoblast number or function. Bone formation is
      modified by systemic hormones such as parathyroid hormone, growth hormone,
      insulin and steroids, and by local factors that act in an antocrine or paracrine
      fashion on the osteoblast. Skeletal cells synthesize platelet-derived growth
      factors and fibroblast growth factors, agents which affect osteoblast cell
      replication. In addition, skeletal cells synthesize insulin-like growth factors
      and transforming growth factors beta, agents which also affect the differentiated
      function of the osteoblast. Systemic and local factors that modify bone formation
      are likely critical in the maintenance of normal bone.

PMID- 8275388
TI  - [Diet of dental students entering university].
AB  - As there are not a lot of data available on the diet of the young adult
      population, we perceived that it would be interesting to study the diet of dental
      students entering university, and to determine if their diet differs according to
      sex. From 1986 to 1992, participating students completed three-day lists of the
      foods they consumed. These lists were reviewed according to the energy content
      and the distribution of proteins, glucides and lipids in the diet. The calcium
      and iron content were calculated, as was the body weight index (P/T2), and then
      compared to the Canadian recommendations and averages. For both males and
      females, the average energy content was slightly lower than recommended. The
      proportion of energy derived from glucides, lipids and proteins was more or less
      the same for both groups, but the glucide content was lower than recommended. The
      ingestion of lipids was just above the national recommendation, while the
      ingestion of proteins, calcium and iron was higher. A similar proportion of
      individuals to the one identified in studies by Health Promotion Canada and Sante
      Quebec was found to be in the lower range of the body weight index (< 20). Many
      fewer, however, were in the 25+ section. As a significant number of female
      students from Asia were in the low body weight index group, it was assumed that
      this index might not be valid for this population.

PMID- 8275389
TI  - Planning pays.

PMID- 8275387
TI  - Role of cytokines in the regulation of bone resorption.
AB  - The process of bone remodeling involves complex interactions between the
      osteoclast, the primary bone-resorbing cell, and other cells in its
      microenvironment. These interactions can regulate bone resorption through two
      processes: (1) effects on the number of osteoclasts present at a given site and
      (2) effects on the bone-resorbing capacity of individual osteoclasts. Cells
      present in the osteoclast microenvironment include marrow stromal cells,
      osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells, as well
      as the osteoclast itself, produce cytokines that can affect osteoclast formation
      and osteoclast activity. In vitro model systems using rodent organ cultures or
      long-term marrow culture systems, and in vivo models have demonstrated that
      cytokines such as interleukin-1, M-CSF, tumor necrosis factor, and interleukin-6
      can stimulate the formation and bone-resorbing capacity of osteoclasts. In
      contrast, cytokines such as interleukin-4, gamma-interferon, and transforming
      factor-beta inhibit both osteoclast formation and osteoclast activity. The
      relative proportions of these cytokines in the marrow microenvironment may play a
      critical role in regulating osteoclast activity. Knowledge of cytokines that
      affect osteoclast formation and activity and their capacity to modulate the bone
      resorbing process should provide critical insights into normal calcium
      homeostasis and disorders of bone turnover such as osteoporosis and Paget's
      disease of bone.

PMID- 8275390
TI  - Dental fraud--a betrayal of trust.

PMID- 8275391
TI  - State of affairs: examining your financial status.

PMID- 8275392
TI  - AIDS and dentistry: a retrospective analysis of the Florida case.

PMID- 8275393
TI  - The fourth canal: its incidence in maxillary first molars.
AB  - The purpose of this study was to determine the frequency with which a fourth
      canal is clinically located, instrumented and obturated in maxillary first
      molars. The results indicate that it can be located, instrumented and filled at
      least 77 per cent of the time. This is an important finding for the general
      practitioner and endodontist alike, as clinical success is directly related to
      the complete debridement and obturation of the root canal system.

PMID- 8275394
TI  - Quantification of the lamina dura.
AB  - The lamina dura continues to be an enigma. It is typically described in the
      scientific literature as being present or absent. This study used digitized
      radiographs in an attempt to quantify the thickness of the lamina dura in
      different regions of the oral cavity in healthy adult patients. Even with the
      potential for multiple variables that could affect the appearance of the lamina
      dura, the results show measurable differences in the thickness of the lamina dura
      in the anterior and posterior teeth, with average widths ranging from 0.22-0.54
      mm.

PMID- 8275395
TI  - Nursing informatics as a needed emphasis in graduate nursing administration
      education: the student perspective.
AB  - The faculty of Northeastern University College of Nursing in Boston, MA have
      initiated a nursing informatics emphasis within the graduate nursing
      administration specialization. This article describes the increasing need for an
      aggregate of information systems educational opportunities for the nursing
      managers of the future, followed by a detailed appraisal of the new informatics
      courses offered in the nursing administration curriculum from the perspective of
      this learner. In addition, the author also describes the merits of pursuing a
      Directed Study practicum, which focused on learning the role accountabilities of
      a hospital-based nursing information systems manager.

PMID- 8275396
TI  - Guidelines for the evaluation of instructional software by hospital nursing
      departments.
AB  - Hospital nursing departments are becoming more receptive to the use of computer
      assisted instruction to facilitate and augment educational requisites for both
      staff and client. Numerous guidelines exist for software assessment, but none has
      been devised specifically for the often inexperienced hospital nursing committee
      charged with software review. This paper introduces the Hospital Oriented
      Instructional Software Evaluation, guidelines developed specifically for hospital
      use.

PMID- 8275397
TI  - Loading a nursing expert system from text: a case study.
AB  - A major bottleneck in the construction of expert systems has traditionally been
      the solicitation and formalization of expertise from the "human expert." As a
      means of reducing this bottleneck, the authors propose the use of "text" as a
      source of knowledge. Acquisition of knowledge from text has not been successful
      thus far, primarily because most text is not presented in a format (rules,
      frames, or logic) that can be directly used to load a knowledge base. The authors
      propose techniques to overcome these inherent problems. This article introduces a
      model for building an expert system that relies on "text" as the source of
      knowledge. The model is introduced via a case study involving the building of a
      nurse expert system designed to replicate the medical diagnostic activities of
      professional nurses.

PMID- 8275398
TI  - Description and initial applications of the Staggers & Parks Nurse-Computer
      Interaction Framework.
AB  - The authors developed a nurse-computer interaction framework by integrating
      concepts from human-computer interaction, nursing informatics, and developmental
      psychology. In this framework, nurses and computers interact in a system of
      mutual influences, with information being the medium of exchange between them.
      Nurse behaviors and computer interface actions occur according to their
      respective characteristics. In turn, the nurse-computer dyad is embedded within a
      nursing context and moves along a nursing informatics developmental trajectory. A
      sample of findings from empirical studies is placed in the framework, and
      framework uses are described.

PMID- 8275400
TI  - Bedside/point-of-care technology: the 'window' into the integrated clinical
      database, Part 6.

PMID- 8275399
TI  - Prototyping a bedside documentation system.
AB  - The implementation of a comprehensive bedside documentation system is a major
      project that demands careful analysis and planning. Since the cost of a typical
      bedside system can easily exceed $3 million, a design oversight could have
      disastrous effects on the benefits of the system.

PMID- 8275402
TI  - Blood donation and HIV.

PMID- 8275401
TI  - Blood transfusion in Canada.

PMID- 8275403
TI  - The Part II examination: more thoughts.

PMID- 8275404
TI  - Local adverse effects of meningococcal vaccine.

PMID- 8275405
TI  - Canadian self-sufficiency in physician resources.

PMID- 8275406
TI  - Role of whole-cell pertussis vaccine in severe local reactions to the preschool
      (fifth) dose of diphtheria-pertussis-tetanus vaccine.
AB  - OBJECTIVE: To estimate the contribution of whole-cell pertussis vaccine to severe
      local reactions after the preschool (fifth) dose of adsorbed diphtheria toxoid
      pertussis vaccine-tetanus toxoid (DPT) vaccine. DESIGN: Double-blind randomized
      controlled trial. SETTING: Urban community. PARTICIPANTS: Volunteer sample of 200
      healthy children 4 to 6 years old who were eligible for the fifth dose of DPT
      vaccine. INTERVENTIONS: Children received, in both arms, either diphtheria toxoid
      tetanus toxoid (DT) and monovalent pertussis vaccines (group A, 99 children) or
      DPT and meningococcal vaccines (group B, 101 children). All were licensed
      products from single lots. The children were assessed 24 hours later by a trained
      observer. Serum samples obtained before vaccination were tested for antibodies to
      tetanus and diphtheria toxins and five pertussis antigens by means of enzyme
      linked immunosorbent assay. MAIN OUTCOME MEASURES: Rates of severe local
      reactions (an area of redness or swelling or both of 50 mm or greater) 24 hours
      after vaccination. Relation between serum antibody levels before vaccination and
      rates of severe local reactions to corresponding vaccines. RESULTS: All of the
      subjects were followed up 24 hours after vaccination. Severe redness was present
      in 38% given DPT vaccine, 29% given intramuscular pertussis vaccine and 9% given
      DT vaccine (p < or = 0.002, three-way comparison). Severe swelling was common
      after vaccination with all three products. After intramuscular pertussis
      vaccination a relation was evident between the prevaccination levels of antibody
      to whole-cell pertussis bacteria and the rates of redness (p < 0.02) but not
      between the prevaccination subcellular antibody levels and the rates of redness.
      CONCLUSION: That pertussis vaccine resembled the DPT vaccine in causing severe
      redness suggests that it is the principal cause of such reactions after DPT
      vaccination. The DT vaccine was also reactogenic; thus, cumulative sensitization
      to one or more of its constituents may be a factor.

PMID- 8275407
TI  - Radioallergosorbent testing for penicillin allergy in family practice.
AB  - OBJECTIVES: To determine (a) the prevalence of patients supposedly allergic to
      penicillin who have a positive radioallergosorbent test (RAST) result for
      penicillin G or V and (b) the predictive power of family physicians' clinical
      judgement that a patient who is supposedly allergic to penicillin will have a
      positive RAST result. DESIGN: Prospective multicentre cross-sectional
      observational study. SETTING: Eleven primary care practices in Newfoundland; 10
      were in a rural setting. PATIENTS: Of 110 consecutive adult patients with a
      supposed allergy to penicillin 97 agreed to participate in the study; 92
      underwent RAST. INTERVENTIONS: Patients helped physicians complete a
      questionnaire and had a venous blood sample taken for the RAST. Physicians
      examined the clinical history and judged whether the patient was likely to have a
      positive RAST result. MEAN OUTCOME MEASURES: Rates of positive and negative RAST
      results for penicillin V and G. RESULTS: Of the 92 patients 8 had a positive RAST
      result and 84 a negative one. The positive predictive power of a "good" clinical
      history (e.g., urticaria, swollen eyes, tongue or lips, or an anaphylactic
      reaction witnessed by a physician) was low (10%); the negative predictive power
      of a "poor" clinical history (e.g., nausea, vomiting, diarrhea, fever,
      nonspecific rash or fainting) was 92%. CONCLUSIONS: Less than 10% of primary care
      patients with a supposed allergy to penicillin will have a positive RAST result.
      In addition, physicians' predictions of allergy in such patients are imprecise.

PMID- 8275408
TI  - Intentional iron overdose: an institutional review.
AB  - OBJECTIVE: To document the frequency of admissions and the outcome of patients
      with a diagnosis of intentional iron overdose to a large urban hospital. DESIGN:
      Retrospective review of hospital records. SETTING: Health Sciences Centre,
      Winnipeg, an 1100-bed primary and tertiary care centre serving a regional
      population of about 1.2 million. PATIENTS: All patients with a discharge
      diagnosis of iron overdose who were admitted from Jan. 1, 1979, to July 1, 1991.
      Of these 113 cases 66 (58%) represented an intentional iron overdose on the basis
      of information derived from the patient, family or friends. MAIN OUTCOME
      MEASURES: Frequency of admissions, length of hospital stay and survival rate.
      RESULTS: Most (53 [80%]) of the 66 patients were females. The mean age was 19.8
      (standard deviation [SD] 6.1) years (range 9 to 48 years). One third of the cases
      were associated with excess alcohol intake. The frequency of hospital admissions
      increased during the study period (1.4 cases per year in the first 5 years and
      9.8 cases per year in the last 5; 5.3 cases per year overall). The mean length of
      hospital stay was 6.8 (SD 12.1) days, and the mortality rate was 10%.
      CONCLUSIONS: Hospital admissions because of intentional iron overdose are
      becoming more frequent in this centre and are associated with appreciable
      morbidity and mortality rates. Prospective studies are required to delineate
      clearly the signs, symptoms and abnormal laboratory findings associated with this
      problem.

PMID- 8275409
TI  - Genetic diagnosis: present and prospects.

PMID- 8275410
TI  - Medicine in the Terezin ghetto: commitment to care amidst a concentration camp's
      horrors.

PMID- 8275411
TI  - Isle of Man provides unique forum for presenting health care grievances.

PMID- 8275412
TI  - MDs should assume more responsibility for managing health care, Royal College
      audience told.

PMID- 8275413
TI  - Epidemic of childhood obesity may cause major public health problems, doctor
      warns.

PMID- 8275414
TI  - The effect of age at diagnosis on outcome in rhabdomyosarcoma.
AB  - BACKGROUND: Survival for rhabdomyosarcoma appears to be more favorable in
      children and adolescents compared with adults. To determine the significance of
      age at diagnosis as a prognostic indicator in rhabdomyosarcoma, we performed a
      retrospective analysis of a combined pediatric and adult rhabdomyosarcoma data
      base. METHODS: Pertinent prognostic variables, including age, TNM stage,
      histopathologic subtype, anatomic site, resectability, radiation to the primary
      site, and dose intensity of chemotherapy, were compared in a Cox proportional
      hazards model with mortality as the outcome variable. RESULTS: Age at diagnosis
      (P = 0.0001) and local tumor invasiveness (P < 0.0001), distant parenchymal
      metastases (P < 0.0001), regional lymph node involvement (P = 0.0027), and
      histopathologic subtype (P = 0.0446) contributed information to the proportional
      hazards model. CONCLUSIONS: Age at diagnosis is an independent predictor of
      outcome in patients with rhabdomyosarcoma along with tumor invasiveness,
      metastases, regional lymph node involvement, and histopathologic subtype.

PMID- 8275415
TI  - Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions.
AB  - BACKGROUND: The increased prevalence of ductal carcinoma in situ (DCIS) has
      produced a growing awareness of the importance of its diverse patterns. These
      differences in pattern have become clinically significant as predictive
      indicators of success for planned local excisions of small DCIS lesions. METHODS:
      The authors reviewed 100 sequentially collected DCIS cases from a consultation
      practice. Recognizing the bias of such a series toward exclusion of easily
      recognizable comedo DCIS, the authors investigated the spectrum of mixed pattern
      lesions to identify variations and common features in the architectural
      arrangement of the various histologic patterns. RESULTS: Patterns of atypical
      ductal hyperplasia (ADH) with specific criteria of recognition were intermixed in
      17 cases (11 cribriform, 1 solid, 1 micropapillary, 4 mixed). Thirty-three cases
      of DCIS consisted of mixed patterns of comedo and noncomedo types. No case of
      comedo DCIS with associated areas of ADH was identified. In all cases of combined
      DCIS and ADH, the more advanced patterns of DCIS were present in the central
      portion of the lesion, with the ADH components arranged peripherally. This
      tendency for the more severely atypical areas to be located centrally was present
      throughout the study. CONCLUSIONS: Different patterns of DCIS are frequently
      present within individual lesions (46 of 100), and the more advanced features of
      architectural atypia are regularly present centrally. This strongly supports the
      hypothesis that these lesions develop from a central focus and expand
      peripherally. Also, those lesions with low-grade DCIS at the periphery may be as
      amenable to local excision for cure as purely low-grade lesions.

PMID- 8275416
TI  - Survival trend after invasive cervical cancer diagnosis in Sweden before and
      after cytologic screening. 1960-1984.
AB  - BACKGROUND: Cytologic screening can reduce mortality from cervical cancer by
      detection and removal of premalignant lesions. Conceivably, mortality is further
      reduced because more women with invasive disease are diagnosed at an earlier,
      curable stage. This hypothesis can be assessed in Sweden, where population-based
      screening programs were introduced successively over about a decade starting in
      1964. METHODS: Record linkages permitted complete follow-up through 1986 of all
      17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960
      through 1984. We analyzed relative survival rates that describe the survival of
      patients after elimination of the effects of causes of death other than cancer of
      the cervix. RESULTS: Prognosis improved substantially in patients younger than
      age 50 years at diagnosis; from 1960-1964 to 1980-1984, the 5-year relative
      survival rate increased from 69.8% to 88.8% at age 20-29 years, from 71.7% to
      85.5% at age 30-39 years, and from 68.6% to 77.9% at age 40-49 years. The excess
      mortality was thus reduced by more than half in patients diagnosed when younger
      than 40 years. In contrast, only slight or no improvement was noted in those
      diagnosed at older ages when screening was less extensive. In all time periods, a
      strong association was found between older age at diagnosis and poorer prognosis.
      CONCLUSION: Although alternative explanations for our findings must be seriously
      considered, the most obvious interpretation is that cytologic screening reduces
      mortality from cervical cancer by earlier diagnosis of invasive disease.

PMID- 8275417
TI  - Clinicopathologic differences between carcinoma in the gastric remnant stump
      after distal partial gastrectomy for benign gastroduodenal lesions and primary
      carcinoma in the upper third of the stomach.
AB  - BACKGROUND: This study evaluated the prognosis of patients with carcinoma in the
      gastric remnant stump after distal gastrectomy for benign disease (stump cancer).
      METHODS: Twenty patients with resected stump cancer were studied and compared
      with 266 patients with resected primary cancer in the upper third of the stomach
      (primary cancer). RESULTS: The percentages of lymph nodes with metastases located
      at the lesser curvature and the left gastric artery, respectively, were 50.0% and
      25.2% in patients with primary cancer and 15.0% and 5.0% in patients with stump
      cancer. In patients with remnant gastric cancer, lymph node metastases at jejunal
      mesentery near anastomotic site were found in 2 of 20 (10.0%). The 5-year
      survival rates were 62.1% and 52.5% for patients with curatively resected primary
      cancer (n = 203) and stump cancer (n = 17), respectively, and there was no
      statistical difference between the two groups. There was a distinct difference in
      terms of patterns of recurrence between patients with curatively resected primary
      cancer and those with stump cancer. The percentages of peritoneal and hematogenic
      metastases, respectively, were 40.6% and 31.3% in primary cancer and 0% and 83.3%
      in stump cancers. CONCLUSION: The lymph flow from the remnant stomach seems to be
      changed by the initial operation, and as a result, in stump cancer, metastatic
      lymph nodes are located at different places from those associated with primary
      cancer. Even when curative surgery is performed in patients with stump cancer, it
      is important to follow up patients and check for possible metastasis to the
      liver.

PMID- 8275418
TI  - Partial nephrectomy for renal cell carcinoma with a normal opposite kidney.
AB  - BACKGROUND: The role of nephron-sparing surgery in patients with unilateral renal
      carcinoma and a normal opposite kidney is controversial. METHODS: The number and
      selection criteria of patients undergoing a partial nephrectomy versus radical
      nephrectomy from 1979 to 1991 were compared. RESULTS: Of 230 patients having
      curative surgery for unilateral renal cell carcinoma, 41 had a partial
      nephrectomy. The percentage of partial compared with total nephrectomies
      performed increased from 8% in 1979-84, to 20% in 1984-88, and 30% in 1989-91.
      The increased number of partial versus radical nephrectomies performed reflected
      an increased detection of small (3.5 cm) incidental renal tumors by radiologic
      imaging. The local recurrence rate was 2.4% (one patient), and the survival rate
      was 95% (average, 3 years). CONCLUSION: Complete local excision of the small
      serendipitous renal tumor is feasible and reasonable in the patient with an
      otherwise normal opposite kidney.

PMID- 8275419
TI  - Hurthle cell carcinoma metastatic to the uvea.
AB  - BACKGROUND: The authors present a case of Hurthle cell carcinoma metastatic to
      the uvea in a patient with known Hurthle cell tumor of the thyroid. The
      fluorescein angiogram suggested a neoplastic lesion, and the collar-button
      configuration resembled a malignant melanoma. However, standardized echography
      revealed high internal reflectivity and an irregular acoustic structure
      suggestive of a metastatic carcinoma. METHODS: The clinical history and
      examination were consistent with the diagnosis of metastatic Hurthle cell
      carcinoma of the eye. Results of a fine-needle aspiration biopsy and
      histopathology of the intraocular lesion confirmed the diagnosis. RESULTS:
      Because this was the patient's better-seeing eye, the tumor was treated with an
      125I radioactive episcleral plaque. Over the subsequent 27 months, the lesion
      demonstrated a gradual regression. CONCLUSIONS: We have not found any previously
      reported cases of Hurthle cell carcinoma of the thyroid metastatic to the eye.
      The diagnosis may be confirmed safely by intraocular aspiration biopsy. The
      lesion is responsive to radioactive plaque application. The origin, pathology,
      and management of this unusual tumor are reviewed.

PMID- 8275420
TI  - The radiographic diagnosis and treatment of paraneoplastic central nervous system
      disease.
AB  - Paraneoplastic nervous system syndromes are being identified with increasing
      frequency because of greater physician awareness and the availability of
      serodiagnostic tests for some syndromes. Frequently, paraneoplastic syndromes
      develop in the setting of an indolent, limited stage, or otherwise occult
      malignancy. As a result, the paraneoplastic disorder often becomes the most
      disabling part of a patient's disease. Effective treatment appears to require
      early identification. For these reasons, the ability to diagnose a paraneoplastic
      syndrome, follow its course, and treat it successfully are important. The authors
      describe four patients with neurologic paraneoplastic syndromes and identical
      magnetic resonance imaging abnormalities. Three patients responded to
      immunosuppressive or immunomodulatory therapy, and in one, corresponding
      radiographic improvement was documented. Strategies for early diagnosis and
      options for treatment of paraneoplastic nervous system disorders are discussed.

PMID- 8275421
TI  - Low rate of ret proto-oncogene activation (PTC/retTPC) in papillary thyroid
      carcinomas from Saudi Arabia.
AB  - BACKGROUND: The ret proto-oncogene activation (PTC/retTPC oncogene) in thyroid
      papillary carcinoma has been reported in different populations with different
      frequencies. Thyroid papillary carcinoma appears to behave more aggressively in
      the Persian Gulf region than elsewhere. In the current study, the frequency of
      PTC/retTPC oncogene in thyroid tumors from Saudi Arabia was investigated.
      METHODS: PTC/retTPC oncogene transcripts were analyzed by the polymerase chain
      reaction amplification of cDNA synthesized by treatment of total RNA with reverse
      transcriptase. Seven multinodular goiters, 1 follicular adenoma, 4 follicular
      carcinomas, 40 papillary carcinomas, and 5 anaplastic carcinomas were studied.
      RESULTS: Only one papillary carcinoma specimen was found to have PTC/retTPC
      oncogene transcripts. The breakpoint of the rearranged PTC/retTPC oncogene is
      identical to that previously described. The PTC/retTPC-positive sample was also
      examined for p53 tumor suppressor gene mutations in exons 5-8. One transitional
      point mutation was detected at codon 161 (GCC to ACC), changing Ala to Thr.
      CONCLUSIONS: This study questions the relevance of PTC/retTPC oncogene in the
      carcinogenesis of thyroid papillary carcinomas in the Saudi population. Genetic
      background among races may contribute to the different frequencies of PTC/retTPC
      oncogene in thyroid papillary carcinoma.

PMID- 8275422
TI  - p53 tumor suppressor oncogene expression in squamous cell carcinoma of the
      hypopharynx.
AB  - BACKGROUND: Although abnormalities of the p53 tumor suppressor oncogene system
      are being detected in many human cancers, the frequency and prognostic
      significance of such events in squamous cell cancer of the head and neck remain
      unknown. METHODS: Immunohistochemical studies were performed on archival tumor
      tissue taken from 43 patients with squamous cell carcinoma of the hypopharynx.
      Statistical analyses examining potential associations between p53 oncoprotein
      accumulation and various clinicopathologic parameters (including survival) were
      conducted. RESULTS: Sixteen (37%) tumors demonstrated strong specific staining
      for p53. Patients whose tumors stained strongly for p53 were significantly
      younger, presented at a more advanced clinical disease stage, and tended to have
      increased expression of epidermal growth factor receptor (P = 0.056). There was
      no correlation between p53 expression and the incidence of multiple primary
      cancers, tumor grade, DNA ploidy, or percent of S-phase. Median survival times
      were 11.6 months and 18.0 months for the p53-positive and p53-negative groups
      (NS). A Cox regression analysis confirmed the lack of significance of p53 in
      overall survival. CONCLUSIONS: These data suggest that although abnormalities of
      the p53 oncoprotein are common in this cancer, this finding is of little clinical
      significance.

PMID- 8275423
TI  - Recurrence at the primary site in head and neck cancer and the significance of
      neck lymph node metastases as a prognostic factor.
AB  - BACKGROUND: Biologic aggressiveness of head and neck carcinoma is reflected in
      its capability to metastasize to regional lymph nodes and its propensity to recur
      after treatment. METHODS: The authors report on 244 patients treated at the
      Department of Otolaryngology-Head and Neck Surgery of the Free University
      Hospital, Amsterdam, The Netherlands, with excision of primary tumor with
      incontinuity neck dissection with or without postoperative radiation therapy
      between January 1973 and July 1986. All patients had surgical margins free of
      tumor. RESULTS: The overall recurrence rate was 12.3%. Stages T3-4 and the
      presence of more than three positive nodes on histopathologic examination were
      associated with a 16.2% and 26.2% incidence in recurrence at the primary site,
      respectively. No prognostic influence arose from primary tumor localization,
      three or fewer positive nodes, extranodal spread, and postoperative radiation
      therapy. CONCLUSIONS: Patients with T3-4 disease and those with more than three
      positive lymph nodes may benefit from novel adjuvant treatment modalities.

PMID- 8275424
TI  - Endothelin-1 as an aggravating factor of disseminated intravascular coagulation
      associated with malignant neoplasms.
AB  - BACKGROUND: Vascular endothelial damage may play an important role in the
      pathophysiology of disseminated intravascular coagulation (DIC), a frequent
      complication of malignant neoplasms. It may mediate a variety of triggering
      events to initiate DIC and platelet aggregation, which in turn leads to
      additional endothelial destruction. If so, endothelin-1 (ET-1), the most potent
      vasoconstrictor of naturally occurring pressor substances known, may leak from
      injured endothelial cells and aggravate the disease process. METHODS: The study
      included 36 patients with various malignant neoplasms in whom DIC developed. The
      authors measured plasma levels of ET-1 and big ET-1, a precursor peptide of ET-1,
      in these patients and compared them with other laboratory abnormalities during
      the course of DIC. RESULTS: Plasma ET-1 and big ET-1 levels were elevated in most
      patients with DIC. When compared with the results of other diagnostic tests,
      elevated plasma big ET-1 was the most frequently found abnormality associated
      with DIC. Elevation of plasma ET-1 and big ET-1 levels was closely related to the
      initiation and progression of DIC and provided a higher degree of sensitivity and
      specificity than did other indicators in assessing patients with cancer and DIC.
      CONCLUSIONS: Vascular endothelial damage with the resultant increases in plasma
      ET-1 and big ET-1 levels is universally associated with DIC caused by malignancy.
      Excessive secretion or leakage of ET-1 and big ET-1 from injured endothelial
      cells may cause vasospasm and aggravate the DIC process by facilitating the
      formation of intravascular microthrombi, ultimately leading to ischemic end-organ
      dysfunction. Plasma ET-1 and big ET-1 are sensitive and specific markers for
      vascular endothelial injury in DIC.

PMID- 8275425
TI  - Cyclosporin enhancement of cisplatin chemotherapy in patients with refractory
      gynecologic cancer. A Gynecologic Oncology Group Study.
AB  - BACKGROUND: Cyclosporin has been demonstrated to reverse resistance to several
      antineoplastic agents including cisplatin in vitro. The purpose of this Phase I
      trial was to study the potential clinical application of cyclosporin modulation
      of cisplatin and to establish a tolerable dose of cyclosporin when combined with
      a standard dose of cisplatin of 75 mg/m2. METHODS: A course of therapy consisted
      of two cyclosporin infusions over 2 hours each, 24 hours apart, with cisplatin
      given 6 hours after the first dose. Treatment was repeated every 21 days.
      Cyclosporin was studied in a Phase I fashion at five different levels, from 1-5
      mg/kg per dose. Twenty patients with refractory gynecologic cancer received 81
      courses of therapy. All patients had received extensive prior chemotherapy
      containing cisplatin. RESULTS: Grade 4 nephrotoxicity was seen in 4 of 20
      patients: 1 treated at 1 mg/kg, 1 at 2 mg/kg, and 2 at 5 mg/kg of cyclosporin.
      The patient treated at the 1 mg/kg level was a partial clinical responder and
      tolerated six courses. The patient at the 2 mg/kg level had received 14 prior
      courses of cisplatin and tolerated only two additional courses before a Grade 4
      renal toxicity developed. Grade 4 nephrotoxicity developed in the two patients
      receiving 5 mg after two courses of chemotherapy. Two of the 20 patients achieved
      a complete response (CR) and 3 patients achieved a partial response (PR), for a
      total response rate of 25% (5 of 20). The two women who achieved CR started
      treatment with symptomatic ascites; one of whom also had multiple pulmonary
      lesions that were no longer evident after three courses of therapy. CONCLUSIONS:
      Cyclosporin at a dose of 4 mg/kg per day given for 2 consecutive days in
      association with 75 mg/m2 of cisplatin can be given with reasonable assurance of
      safety.

PMID- 8275426
TI  - Thyroid lymphoma. The case for combined modality therapy.
AB  - BACKGROUND: Radiation therapy with or without surgery is generally considered
      standard treatment for lymphoma of the thyroid. Because of the small number of
      cases, the role of chemotherapy or combined modality treatment is difficult to
      determine. METHODS: The published literature was analyzed, supplemented by a
      series from Yale, for the incidence of local and distant relapse after radiation
      therapy, chemotherapy, or combined modality treatment for Stage I-II thyroid
      lymphoma. Patients with advanced disease or in whom radiation was probably
      inadequate were excluded. Only patients receiving an anthracyline-based regimen
      were considered in the group with chemotherapy. Patients receiving single agents
      or non-anthracycline-based regimens were excluded from analysis or, if they also
      received radiation, were included in the group that received radiation only.
      RESULTS: Including a series from Yale, a total of 211 patients with Stage IE and
      IIE thyroid lymphoma were identified. Distant and overall relapse rate were
      significantly lower in the group that received combined modality treatment. Local
      relapse was also less, but the difference was not statistically significant. In a
      small number of patients with disease confined to the neck, the results with
      radiation were similar to combined modality treatment if the mediastinum was
      included in the treatment port. CONCLUSION: Although mucosa-associated lymphoma
      tissue lymphomas are thought to have a low distant recurrence rate and are
      therefore often treated with local therapy alone, a review of the published
      literature suggests that 30% of thyroid lymphomas with clinically localized
      disease will have a distant relapse. The addition of chemotherapy to radiation
      significantly lowered distant and overall recurrence.

PMID- 8275427
TI  - Lymph node classification systems in cutaneous T-cell lymphoma. Evidence for the
      utility of the Working Formulation of Non-Hodgkin's Lymphomas for Clinical Usage.
AB  - BACKGROUND: This study was undertaken to compare three classification schemes
      used to evaluate lymph nodes (LN) obtained from patients with cutaneous T-cell
      lymphoma (CTCL): a modified Rappaport classification, the National Cancer
      Institute-Veterans Administration (NCI-VA) classification based on the relative
      numbers of cerebriform cells in the paracortical areas, and the Dutch
      classification based on the presence of cerebriform cells with large nuclei in
      mycosis fungoides (MF) and diffuse infiltration by cerebriform cells in Sezary
      syndrome. METHODS: A study set of 195 LN obtained from patients with CTCL (MF,
      Sezary syndrome, and nonepidermotropic T-cell lymphomas) and 14 LN from patients
      with benign dermatoses was reviewed independently by three groups of pathologists
      familiar with each classification system. RESULTS: Each classification system
      provided useful prognostic information. However, contrary to prior reports, no
      significant difference in survival was apparent in patients with uneffaced LN
      when classified according to the NCI-VA (LN0-2 versus LN3) or Dutch (Gr0-1 versus
      Gr2) ratings. In addition, all classification systems demonstrated a poor
      survival time associated with effaced LN. By combining results from the modified
      Rappaport and Dutch classifications, three prognostic groups could be identified
      based on cell morphology: a low-grade category with a small cell histologic
      subtype (median survival time, 40 months); a high-grade immunoblastic subtype
      (median survival time, 9 months) composed of cells with an oval nucleus
      containing a large, usually solitary central nucleolus; and an intermediate-grade
      category composed of all cases without the distinctive small cell and
      immunoblastic morphologies (median survival time, 26 months). CONCLUSIONS: The
      authors propose that clearly involved LN in CTCL can be categorized on the basis
      of cell morphology into prognostic groups analogous to what has been proposed for
      the Working Formulation for Non-Hodgkin's Lymphomas for Clinical Usage.

PMID- 8275428
TI  - Treatment of overt isolated testicular relapse in children on therapy for acute
      lymphoblastic leukemia. A report from the Childrens Cancer Group.
AB  - BACKGROUND: Fifty-seven children with acute lymphoblastic leukemia (ALL)
      receiving therapy who experienced overt isolated testicular relapse while in bone
      marrow remission were entered into a study that featured an intensive retreatment
      regimen. METHODS: The objective was to determine whether a change in chemotherapy
      and local irradiation would prevent subsequent marrow relapse and increase the
      survival rate. The regimens used (modified Berlin-Frankfurt-Munster or modified
      New York) delivered acceptable therapy based on analyses of toxicity data.
      RESULTS: Overall survival at 5 years from the time of testicular relapse was 47%,
      with an event-free survival of 43%. Events have been documented in 28 of 55
      evaluable children. Analysis of these patients revealed that 23 children had bone
      marrow relapse, 4 children had central nervous system relapse, and 1 child had
      testicular relapse. In addition, two patients were removed from the study for
      toxicity, one child for infection (mucormycosis), and five children had a bone
      marrow transplantation while in remission and became ineligible to continue in
      the study. Two children were removed at the request of their parents, and nine
      children were lost to follow-up. CONCLUSION: Because of their high risk of
      developing systemic relapse, boys with ALL who experience isolated overt
      testicular relapse during active therapy should be retreated with intensive
      treatment.

PMID- 8275429
TI  - Defining the invasive phenotype of proximal gastric cancer cells.
AB  - BACKGROUND: Adenocarcinoma of the proximal stomach is now the most rapidly rising
      cancer among men in the United States. The development of metastases is the major
      cause of morbidity and mortality for this aggressive disease. The mechanisms by
      which tumor cells invade the basement membrane are unknown for this disease. We
      have identified and established 5 invasive and noninvasive adenocarcinoma cell
      lines arising from the proximal stomach, which can be used to examine the
      mechanisms involved in tumor cell invasion. METHODS: The expression of factors
      associated with tumor cell attachment, proteolysis, and inhibition of proteolysis
      was determined by reverse transcription of mRNA to cDNA and subsequent
      amplification by the polymerase chain reaction. In addition, cells were examined
      for morphologic changes by scanning electron microscopy. RESULTS: Invasive
      proximal gastric cancer cells express the 72-kD form of collagenase type IV,
      whereas the noninvasive cells do not. Other factors examined (including the
      laminin receptor, cathepsin B, cathepsin L, urokinase-type plasminogen activator,
      and tissue inhibitor metalloproteinases) are expressed by both invasive and
      noninvasive gastric cancer cells, whereas collagenase type IV 92-kD form is not
      expressed by any of the cells examined. In addition, scanning electron microscopy
      revealed that all the invasive cell lines exhibit long cytoplasmic extensions.
      The noninvasive cells express short cytoplasmic projections and are rounder than
      the invasive proximal gastric cancer cell lines. CONCLUSIONS: There are distinct
      phenotypic differences between invasive and noninvasive proximal gastric cancer
      cell lines both at the level of expression of mRNA for collagenase Type IV 72-kD
      and at the level of scanning electron microscopy with the expression of
      cytoplasmic projections. Clinical outcome may be associated with these phenotypic
      differences.

PMID- 8275430
TI  - Non-Hodgkin's lymphoma in four children infected with the human immunodeficiency
      virus. Association with Epstein-Barr Virus and treatment.
AB  - BACKGROUND: Reports on lymphoid malignancy and its treatment in children infected
      with human immunodeficiency virus (HIV) are limited. METHODS: Antibodies to
      Epstein-Barr virus (EBV) were detected by indirect immunofluorescence. DNA was
      extracted from peripheral blood lymphocytes or biopsy specimens. Polymerase chain
      reaction was run using primers for EBV. Reaction products underwent Southern blot
      analysis to confirm EBV specificity. Tumor clonality was assessed by
      immunohistochemistry and by Southern blot analysis of immunoglobulin heavy-chain
      and T-cell receptor beta-gene rearrangement. RESULTS: Within 1 year, non
      Hodgkin's lymphoma (NHL) was diagnosed in four children infected with HIV. All
      four were EBV-seropositive and had detectable EBV DNA in peripheral blood
      lymphocytes. The EBV-linked disorders lymphoid interstitial pneumonia and
      recurrent parotid enlargement preceded NHL in three and two of the children,
      respectively. In all four patients, NHL involved at one time the central nervous
      system (CNS). All three tested NHL tissues were positive for EBV DNA: A 12-week
      course of chemotherapy given to two children resulted in rapid tumor regression.
      One of these children experienced meningeal relapse and died 16 months after
      diagnosis. The other child, who in addition received local irradiation of the
      affected eye and who underwent surgical removal of the involved ovaries, has been
      in continuous remission for 20 months. CONCLUSIONS: EBV-associated NHL may be
      seen more frequently in pediatric patients with HIV. Treatment protocols taking
      into account NHL propensity for the CNS in this age group need to be developed.

PMID- 8275431
TI  - Cancer-associated fasciitis panniculitis.
AB  - BACKGROUND: Eosinophilic fasciitis and the related fasciitis panniculitis
      syndrome (FPS) are the clinical and morphologic expression of a variety of
      disorders, of which chronic inflammation and fibrous thickening of the
      subcutaneous septa, fascia, and perimysium are common. FPS in patients with
      cancer has been reported sporadically. METHODS: In the course of our studies of
      FPS we have encountered three patients who had an associated neoplasia. Nine
      reports of patients have been taken from the literature. The clinical and
      histologic data of FPS in the 12 patients were analyzed in the search of
      distinctive features from FPS in patients with no evidence of malignancy.
      RESULTS: Among patients with cancer-associated FPS there was a female
      predominance (8 patients), predilection for hematolymphatic malignancies (9
      patients), precedence of the FPS to cancer diagnosis (10 patients) by a median
      lag time of 1 year, and unresponsiveness to prednisone therapy in most patients
      (7 of 8 patients). CONCLUSIONS: Cancer-associated FPS has several characteristics
      of a paraneoplastic syndrome: it occurs at a distance from the tumor, certain
      types of tumors are overrepresented among patients with FPS, it evolves in
      concert with the neoplasia, and it sometimes remits after successful cancer
      surgery. In contrast to idiopathic FPS, cancer-associated FPS shows a female
      predominance, and it usually fails to respond to corticotherapy.

PMID- 8275432
TI  - A phase I trial of weekly lomustine in patients with advanced cancer.
AB  - BACKGROUND: Lomustine is a commercially available chloroethyl nitrosourea
      compound whose antitumor activity in vitro and in animal tumor models exceeds its
      activity in humans. Part of the poor clinical performance of this drug may be
      explained by dose-limiting subjective toxicity observed with the standard
      schedule of one oral dose of approximately 130 mg/m2 every 6-8 weeks. METHODS:
      Twenty patients were enrolled in a Phase I clinical trial of weekly oral
      lomustine. The first dose level was 24 mg/m2, with subsequent dose increases in
      increments of 6 mg/m2. Intrapatient dose escalations were allowed if there were
      no toxic reactions noted after 12 weekly doses. RESULTS: The dose-limiting toxic
      effect was the development of thrombocytopenia in 35% of patients (6 of 17)
      treated at 30 mg/m2 after a median of 12 weekly doses (range, 5-20 weeks),
      whereas in 18% of patients (3 of 17), neutropenia developed after a median of 12
      weeks (range, 9-22 weeks). Grade 3 or Grade 4 hematologic toxicity developed in
      three of three patients whose doses were escalated to 36 mg/m2/week after showing
      no evidence of toxicity for 12-16 weeks at 30 mg/m2/week. Partial remission was
      observed in two patients with malignant melanoma, and stable disease was observed
      in two patients with hypernephroma. Nausea, vomiting, and malaise were not
      significant complications of treatment. CONCLUSION: Lomustine can be administered
      at a dose of 30 mg/m2/week for 12+ weeks to patients with cancer who have
      received previous treatment with minimal toxicity while retaining antitumor
      activity.

PMID- 8275433
TI  - Ifosfamide-induced hyperpigmentation.

PMID- 8275434
TI  - High frequency of allelic deletion on chromosome 17p in advanced colorectal
      cancer.
AB  - BACKGROUND: Colorectal cancers often show allelic loss of chromosomes 5q and 17p,
      regions where the tumor suppressor genes p53 and adenomatous polyposis coli are
      known to reside. Currently, the inactivation of tumor suppressor genes and the
      activation of oncogenes are considered major events involved in tumor
      development. According to a recent genetic model, ras gene mutations and allelic
      deletion of chromosome 5q are early changes, whereas chromosome 17p and 18q
      deletions are late changes in colorectal tumorigenesis. It has been shown that
      17p and 18q deletions are associated with an increased tendency of disease
      dissemination in colorectal cancer. Most of the studies on allelic deletion in
      colorectal cancer were undertaken with Western population cohorts. The authors
      examined the association of chromosomes 5q and 17p deletions with clinical
      parameters, including metastasis in a predominantly Chinese population with a
      high incidence of colorectal cancer. METHOD: Allelic deletion was studied with
      the restriction fragment length polymorphism technique in tumors from 102 and 100
      sporadic colorectal cancer cases for chromosomes 5q and 17p, respectively. Probes
      pi 227 and ECB27 were used for chromosome 5q, and probe YNZ22.1 was used for
      chromosome 17p. RESULTS: 5q Deletion was found in 33% of informative cases,
      whereas 17p deletion was seen in 69% of informative cases. 17p Allelic loss
      showed significant association with Dukes' Stage D as well as the presence of
      distant metastasis, whereas 5q deletion showed no such association. CONCLUSION:
      Allelic loss on chromosome 17p may be a useful prognostic marker in cases of
      colorectal cancer.

PMID- 8275435
TI  - Elevated content of phospholipase C-gamma 1 in colorectal cancer tissues.
AB  - BACKGROUND: Phospholipase C isozymes (PLC) play a role in ligand-mediated signal
      transduction for cellular activity, such as proliferation and differentiation.
      However, the biologic significance of their molecules in carcinogenesis or tumor
      progression is yet to be determined. METHODS: Using PLC isozyme-specific
      antibodies, the relative content of PLC in human colorectal carcinomas and in
      normal colonic mucosa was examined. RESULTS: Immunoreactive analysis revealed
      considerably higher levels of PLC-gamma 1 protein in 15 of 17 colorectal
      carcinomas and little difference in PLC-beta 1 or PLC-gamma 1 content compared
      with normal colorectal tissues. By radioimmunoassay and Western blotting, PLC
      gamma 1 showed three-fold to fourfold more expression in carcinomas than that in
      normal tissues. CONCLUSION: Although factors that might influence the level of
      PLC-gamma 1 expression in colorectal carcinomas still remain obscure, the fact
      that most colorectal carcinomas display elevated levels of PLC-gamma 1 expression
      implies that PLC-gamma 1 may play an important role in proliferation of
      colorectal carcinoma cells.

PMID- 8275436
TI  - Detection of minus-strand hepatitis C virus RNA in tumor tissues of
      hepatocellular carcinoma.
AB  - BACKGROUND: Recently, the detection of hepatitis C virus (HCV) antibody has been
      widely performed for clinical serum testing of HCV infection and can be
      identified in most hepatocellular carcinoma (HCC) cases in Japan. In the current
      study, the authors detected not only plus-strand but also minus-strand HCV RNA as
      a template for RNA replication in hepatocytes in the resected tumors of HCC, and
      they investigated those significant for HCC. METHODS: The plus-strand and minus
      strand HCV RNA were detected using reverse transcription-polymerase chain
      reaction after the extraction of RNA from the tumor and nontumor tissues of
      hepatectomized liver, respectively. RESULTS: The detection of HCV RNA in liver
      tissues from hepatectomized specimens of 20 cases was as follows: in nontumor
      regions, both of the plus- and minus-strand HCV RNA were detected in 14 cases.
      Among those cases, plus- and minus-strand HCV RNA were detected in 11 cases, and
      in another 2 cases, only plus-strand HCV RNA was found in the tumor regions.
      CONCLUSIONS: These results suggest that HCV RNA is able to replicate in tumor
      tissues of HCC and may be involved in the development of HCC and also that HCV in
      remnant hepatocytes may cause the recurrence of HCC as secondary carcinogenesis
      after hepatectomy.

PMID- 8275437
TI  - Phase II trial of gemcitabine in patients with advanced gastric cancer.
AB  - BACKGROUND: Approximately 22,000 new cases of gastric cancer are diagnosed each
      year in the United States, most of which are advanced disease and thus are not
      curable by surgery. Chemotherapy has had little impact on patient survival.
      Consequently, the evaluation of new agents is needed. Gemcitabine, a cytosine
      arabinoside analogue, was evaluated in a Phase II trial to assess its efficacy in
      previously untreated patients with advanced gastric cancer. METHODS: Patients
      were treated with weekly gemcitabine, 800 mg/m2, for 3 consecutive weeks,
      followed by a 1-week rest period. Eighteen patients were enrolled. Fifteen
      patients were evaluable for response; 2 patients refused therapy before the
      completion of one cycle of treatment, and one patient was found to have
      nonmeasurable disease. RESULTS: No major objective responses were seen. Two minor
      responses occurred. One patient with a minor response was removed from the study
      at his request after ten cycles of treatment. The other patient remains on the
      study with stable disease at more than 17 months. Toxicities on this study were
      mild. Median leukocyte count and platelet nadirs were 5.0 (range, 2.2-51.0) and
      234,000/microliters (range, 59,000-554,000/microliters), respectively.
      CONCLUSION: Gemcitabine at this dose and schedule has no significant antitumor
      activity in gastric cancer.

PMID- 8275438
TI  - Interleukin-6 in transcatheter arterial embolization for patients with
      hepatocellular carcinoma. Effects of serine protease inhibitor.
AB  - BACKGROUND: Modulation of serum levels of circulating cytokines and inflammatory
      responses with a serine protease inhibitor was studied in 34 patients with
      hepatocellular carcinoma (HCC) after transcatheter arterial embolization (TAE).
      METHODS: The 34 patients were randomly divided into two groups: 17 patients
      received 500 mg gabexate mesilate, a serine protease inhibitor, intravenously
      twice a day for 5 days after TAE, and the remaining 17 patients did not receive
      the drug. RESULTS: In the patients not given the drug, circulating interleukin-6
      (IL-6) markedly increased 1 day after TAE, reached a peak (approximately 8 times
      the pretreatment value) after 4 days, and remained elevated 7 days after TAE. In
      comparison, in the patients given the drug, circulating IL-6 was at a
      significantly lower level at 4 and 7 days after TAE (P < 0.05, respectively).
      Both groups did not show significant change in circulating interleukin-1 beta (IL
      1 beta) and tumor necrosis factor alpha (TNF alpha) during the week after TAE.
      The drug also showed a tendency to keep patient temperature below 38 degrees C,
      and the elevation of serum C-reactive protein (CRP) concentration to less than 1
      mg/dl after TAE (P < 0.05, respectively). CONCLUSIONS: The serum level of
      circulating IL-6 can be modulated by serine protease inhibitor, and this may
      contribute to suppressing inflammatory responses, such as fever and acute-phase
      protein synthesis, in the liver after TAE.

PMID- 8275439
TI  - Factors influencing survival after resection of pancreatic cancer. A DNA analysis
      and a histomorphologic study.
AB  - BACKGROUND: The influence of DNA content on prognosis in stomach cancer has been
      investigated rarely, and the results are controversial. METHOD: The prognostic
      relevance of the DNA content and histomorphologic parameters was evaluated in 41
      patients after resection of pancreatic cancer. RESULTS: In the univariate
      analysis, the DNA content, tumor size, lymph node status, tumor stage, nuclear
      grade, and type of resection had a statistically significant influence on the
      prognosis. No association was found between the DNA content and the
      histomorphologic features. Apart from the operative procedure, the DNA content
      was the strongest indicator of prognosis in the multivariate analysis.
      CONCLUSIONS: Further investigations are necessary to find out if DNA analysis can
      be performed preoperatively on material obtained by fine-needle aspiration.

PMID- 8275440
TI  - Cardiac synovial sarcoma with translocation (X;18) associated with asbestos
      exposure.
AB  - A primary cardiac spindle cell tumor with immunoreactivity for keratin proteins
      is reported. Cytogenetic analysis of the tumor demonstrated a translocation
      (X;18), an aberration almost exclusively reported in synovial sarcomas.
      Postmortem examination revealed amphibole asbestos within the lungs and
      diaphragmatic pleural plaques indicative of asbestos exposure. These findings
      raise questions about the possible causation of this tumor.

PMID- 8275441
TI  - High doses of intrapleural cisplatin in a case of malignant pleural mesothelioma.
      Clinical observations and pharmacokinetic analyses.
AB  - BACKGROUND: The authors report a feasibility study of intrapleural cisplatin in a
      patient with inoperable malignant pleural mesothelioma. METHODS: Total and
      filterable platinum in pleural effusion and in plasma were monitored for two
      intrapleural courses of 120 mg/m2 cisplatin, and a weekly schedule was adopted.
      Platinum concentrations in pleural effusion, plasma, and urine were determined by
      flameless atomic absorption spectroscopy. RESULTS: A lower peak of filterable
      platinum in plasma, a decrease in systemic filterable platinum exposure (AUC
      [area under the concentration-time curve]), and a greater pleural exposure to
      filterable platinum were observed after Course 2 compared with Course 1. After
      the second cycle of intrapleural treatment, the systemic AUC for filterable
      platinum was reduced by 40%. CONCLUSIONS: The authors' findings may have some
      implications for the clinical use of intrapleural chemotherapy with high doses of
      cisplatin. Both infusions of cisplatin were generally well tolerated by the
      patient and were associated with the local pharmacologic advantage of sustained
      exposure to cisplatin of the pleural cavity. No sign of myelosuppression,
      neuropathy, or ototoxicity was observed, and acute toxicity consisted of mild
      nausea, vomiting, and prolonged anorexia. A transient presence of granular casts
      was the only observed nephrotoxic effect of cisplatin. Excellent local control of
      the disease with absence of recurrence of the effusion was observed.

PMID- 8275442
TI  - Nativity, complications, and pathology are determinants of surgical results for
      gastric cancer.
AB  - BACKGROUND: About half the patients involved in the current study were born
      outside of the United States. Epidemiologic and histologic features and survival
      estimates were compared with persons born in the United States. Results of
      gastrectomy with lymph node dissection were studied. METHODS: Records of 187
      patients with adenocarcinoma of the stomach were reviewed. Seventy-six with a
      curative gastrectomy were staged retrospectively. Univariate and multivariate
      analyses were done. RESULTS: Seventy-six percent of histologically reviewed
      curative resections had the intestinal subtype with the same frequency in U.S.
      born and foreign-born patients. Fewer patients with proximal third lesions were
      foreign born. Thirty-six percent had complications. The overall 5-year Kaplan
      Meier survival estimate was 46%: 77% for patients with negative nodes and 33% for
      patients with positive nodes. N1 survival estimate was 44%; N2, 25%; N3(M1), 0%.
      All six patients with early gastric cancer are alive 50-147 months after surgery.
      Other stage I patients had estimated survival of 65%; Stage II, 52%; Stage III,
      40%; and Stage IV, 0%. Multivariate analysis revealed four significant prognostic
      variables: nativity, histologic subgroup, presence of complications, and number
      of positive nodes. CONCLUSIONS: Proximal gastric cancer was more common in U.S.
      born persons. Gastric cancer may be more malignant in U.S.-born persons than in
      foreign-born persons because their survival was significantly poorer.
      Complications, a significant adverse factor, were more common in U.S. series.
      Pancreatectomy with gastrectomy is rarely indicated, because microscopic
      involvement is rare and complications frequent. The prognostic advantage of a
      regional lymphadenectomy remains unclear.

PMID- 8275443
TI  - Prognostic significance of the blast self-renewal capacity in patients with acute
      myeloid leukemia.
AB  - BACKGROUND: The proliferation of leukemic cells in acute myeloid leukemia (AML)
      is supported by a small subpopulation of leukemic blast progenitors, which can be
      detected in methylcellulose and suspension cultures. It is important to determine
      the association between the biologic properties of leukemic blast progenitors and
      the clinical prognosis of patients with AML. METHODS: Ninety-five patients with
      AML and two patients with chronic myelocytic leukemia in blast crisis were
      studied. T-cell depleted mononuclear cells obtained from the peripheral blood
      cells were cultured in both methylcellulose and suspension cultures. In
      methylcellulose culture, primary blast colony formation (PE1) and secondary blast
      colony formation (PE2) were enumerated. The recovery of clonogenic cells was
      determined in suspension culture. The association between PE1, PE2, or clonogenic
      cell recovery in suspension and the remission induction outcome or survival
      duration of the patients were examined. RESULTS: PE1 was not associated with the
      remission induction outcome. PE2 and clonogenic cells recovered in suspension
      were significantly associated with the remission induction. Furthermore, the
      survival duration of the patients who achieved complete remission was associated
      significantly with the number of clonogenic cells recovered in suspension.
      CONCLUSIONS: PE1 reflects the terminal divisions of leukemic blast progenitors,
      whereas PE2 and the recovery of clonogenic cells in suspension culture are
      considered to reflect the self-renewal of leukemic blast progenitors. The results
      suggest that the self-renewal capacity of leukemic blast progenitors is
      predictive of not only remission induction outcome but also survival duration of
      patients with AML.

PMID- 8275444
TI  - Chemohormone therapy of metastatic melanoma with megestrol acetate plus
      dacarbazine, carmustine, and cisplatin.
AB  - BACKGROUND: Chemotherapy with dacarbazine, carmustine, and cisplatin produces a
      modest objective response rate in melanoma. Megestrol acetate may ameliorate
      cachexia, abrogate drug resistance, and increase survival time in melanoma.
      METHODS: Nineteen patients with metastatic melanoma (16 evaluable) treated with
      dacarbazine (220 mg/m2/day for 3 days, intravenously [IV]), cisplatin (25
      mg/m2/day for 3 days IV) every 3 weeks, and carmustine (150 mg/m2 IV single dose
      every 6 weeks) together with megestrol acetate (160 mg/day by mouth continuously)
      starting 2 days before chemotherapy. RESULTS: This regimen was well tolerated and
      resulted in a mean net weight gain of 1.45 kg. A 47% objective response rate was
      observed in all patients, including visceral sites of response, with a 39+ week
      median duration of response and median survival time of 16.7+ months in all
      evaluable patients. CONCLUSIONS: In this small Phase II study, the authors showed
      that megestrol acetate may contribute to a high objective response rate and
      prolonged median survival when used with a chemotherapy regimen of dacarbazine,
      carmustine, and cisplatin.

PMID- 8275445
TI  - Deletion 7q22 in uterine leiomyoma. A cytogenetic review.
AB  - The cytogenetic patterns of uterine leiomyomas have been extensively
      investigated, and cases characterized by specific clonal changes have been
      documented in detail. In these tumors one of the cytogenetic changes frequently
      observed has been a del(7), particularly del(7)(q22), usually as a sole anomaly.
      This is confirmed by our experience and by reports in the literature. The fact
      that del(7) is one of the most common abnormalities in leiomyoma raises the
      question of its role in tumor development. The main purpose of this review is to
      analyze the above aspect and to interpret its possible meaning. Our findings on
      cytogenetic abnormalities of chromosome 7 in leiomyoma, together with those
      reported in the literature, are reviewed and discussed. A listing of the genes
      located at 7q22 is also presented.

PMID- 8275447
TI  - A case of ins(3;4) in myelogenous leukemia.

PMID- 8275446
TI  - Inversion (14)(q11q32) in a case of acute myeloid leukemia expressing lymphoid
      associated antigens.

PMID- 8275448
TI  - Cloning and characterization of the human t(3;6)(p14;p11) translocation
      breakpoint associated with hematologic malignancies.
AB  - The t(3;6)(p14;p11) chromosome translocation was identified in a family in which
      three members developed hematologic malignancies. To help characterize the region
      on chromosome 3 surrounding this translocation breakpoint, two flanking lambda
      clones, MS156 and MJ1525, were linked by pulsed-field gel electrophoresis to the
      same 510-kb NotI fragment on chromosome 3. MS156 was localized to a region
      proximal to the breakpoint of a der(3) chromosome somatic cell hybrid (derived
      from the t(3;6) cell line), and MJ1525 localized distal to the breakpoint. MJ1525
      was used to screen the CEPH yeast artificial chromosome (YAC) library, which
      revealed a YAC, 195F3, that spanned the breakpoint. Subcloning into Lambda DASH
      II and production of a contiguous array of overlapping lambda clones revealed a
      clone, L17, that spanned the breakpoint. A rare restriction endonuclease map for
      the YAC 195F3 was constructed, and multiple clusters of rare restriction sites
      within the YAC were identified, possibly indicating the disruption of a gene by
      the t(3;6) translocation breakpoint.

PMID- 8275449
TI  - Jumping translocations of 1q in Burkitt lymphoma and acute nonlymphocytic
      leukemia.
AB  - "Jumping translocations" have been observed mostly in cultured cells. Reports of
      such translocations in hematologic malignancies are few, and the associated
      clinical picture is unclear. We report three cases of hematologic malignancies
      with various unbalanced translocations (so-called jumping translocation)
      involving trisomy of the long arm of chromosome 1. The first case was a 13-year
      old boy with Burkitt lymphoma who showed a very aggressive clinical course. The
      second case was a 10-month-old girl with acute nonlymphocytic leukemia [ANNL,
      French-American-British (FAB) classification M0] who had high risk factors,
      including hyperleukocytosis with a peripheral white blood cell (WBC) count of
      300,000/microliters, and who died 7 months after diagnosis. The third case was a
      6-year-old boy with Burkitt-like leukemia whose first remission lasted only 1
      month. Only 10 cases with jumping translocations, including two cases with
      Burkitt-like leukemia/lymphoma, have been reported previously. This rare
      phenomenon may occur with increased frequency in Burkitt-like leukemia/lymphoma
      and may be an adverse prognostic factor.

PMID- 8275450
TI  - Chromosome instability and the FAMMM syndrome.
AB  - Our study involved two extended familial atypical multiple mole melanoma (FAMMM)
      kindreds wherein a sufficient number of informative, high genetic risk, and
      affected patients enabled collection of pertinent tissue samples (normal
      skin/fibroblasts and atypical nevi/melanocytes) for cytogenetic analysis, and
      peripheral blood lymphocytes for DNA usage for linkage studies. We observed
      marked chromosome instability, as evidence by increased frequencies of cells with
      chromosomal rearrangements (translocations, deletions, and inversions) in cell
      cultures from atypical nevi and normal skin. There was no evidence of linkage of
      the FAMMM disease locus to any of the markers for the short arm of chromosome 1p
      in these two families. Well-characterized FAMMM kindreds provide an opportunity
      for biomarker investigations for elucidating heterogeneity and, ultimately,
      improving cancer control.

PMID- 8275451
TI  - Cytogenetic analysis of 109 pediatric central nervous system tumors.
AB  - Reports of cytogenetic abnormalities in pediatric central nervous system (CNS)
      tumors are important for collection and comparison of large numbers of karyotypes
      of primary CNS neoplasms to produce statistically significant correlations. We
      report cytogenetic results of 119 samples of pediatric CNS tumors from 109
      patients. Tumors included 33 low-grade astrocytomas, 18 high-grade astrocytomas,
      14 gangliogliomas, 13 ependymomas, 17 primitive neuroectodermal tumors (PNET),
      three choroid plexus papillomas and carcinomas, and a miscellaneous group of 20
      rare primary CNS tumors and metastases. In each group, cytogenetic results were
      correlated with histologic subtype and survival. The study indicated specific
      chromosome abnormalities in different groups of tumors. Low-grade astrocytomas
      showed mostly numeric abnormalities with gains of chromosome 7, high-grade
      astrocytomas showed differences from karyotypic changes observed in adults in
      lacking double minutes (dmin) and monosomy 10. The ependymoma group showed the
      largest proportion of abnormal karyotypes with frequent involvement of chromosome
      6 and 16. Chromosome 6 was the single most common abnormal chromosome in this
      study, closely followed by chromosomes 1 and 11. Pediatric CNS neoplasms differ
      from adult tumors cytogenetically as well as histologically and biologically.

PMID- 8275452
TI  - Tetrasomy 8 in acute monoblastic leukemia (AML-M5a) with myelosarcomatosis of the
      skin.
AB  - We report a new case with isolated tetrasomy 8, an 82-year-old female patient in
      whom multiple disseminated nodular skin infiltrations up to 5 cm in diameter
      preceded acute monoblastic leukemia (AML-M5a). Despite an initial response to
      chemotherapy and radiotherapy, the patient died 1 year after diagnosis of
      relapsed leukemia. To assess the size of the tetrasomic clone, fluorescence in
      situ hybridization (FISH) analysis with a centromere-specific chromosome 8 probe
      was performed. Seventy percent of interphase cells showed four signals and 22%
      showed three signals. Because this trisomic clone was not detected by
      conventional cytogenetics, tetrasomic cells may have a proliferation advantage in
      vitro. Whether tetrasomy 8 arises from a simultaneous mitotic nondisjunction of
      both chromosomes 8 during one cell division or evolves secondarily from trisomy 8
      through a second mitotic error is not known. Alternatively, trisomy 8 may
      originate from tetrasomy 8 by loss of one chromosome 8.

PMID- 8275453
TI  - Cell lines derived from ultraviolet radiation-induced benign melanocytic nevi in
      Monodelphis domestica exhibit cytogenetic aneuploidy.
AB  - The gray short-tailed opossum, Monodelphis domestica, develops dermal melanocytic
      nevi (MN) after long-term chronic exposure to UVB (midwavelength ultraviolet
      radiation) alone. We developed cell lines from six UVB-induced dermal benign
      melanocytic lesion biopsies. One of the MN was determined histologically to be a
      benign melanoma (BM), whereas the remainder were benign melanocytic hyperplasias
      (MH). The cell lines were not tumorigenic when injected subcutaneously into
      athymic nude mice. Protein extracts prepared from these cell lines were analyzed
      electrophoretically on polyacrylamide gels and protease zymograms in preliminary
      attempts to identify protein and protease markers for pathogenesis. Cytogenetic
      analyses showed that half (three of six) of the MN cell lines exhibited
      aneuploidy involving extra copies of chromosomes 3, 5, 7, and/or 8. This result
      suggests that nonrandom aneuploidy can be an early event in chronic UVB induction
      of benign dermal melanocytic lesions. Karyotyping also showed a centromeric
      variant of chromosome 7 in some animals, which was confirmed to be
      constitutional. These Monodelphis cell lines will be valuable reagents for future
      studies of UVB-induced damage to mammalian skin.

PMID- 8275454
TI  - Partial trisomy of 3q detected by chromosome painting in a case of juvenile
      chronic myelomonocytic leukemia.
AB  - Juvenile chronic myelomonocytic leukemia (JCMMoL) is a rare disease with no
      specific type of chromosome aberration yet delineated. We report a 2-year-old boy
      who had in his leukemic bone marrow (BM) and peripheral blood (PB) cells the
      46,XY,der(15)t(3;15)(q13.1;q26) karyotype. Phytohemagglutinin (PHA)-stimulated
      lymphocytes of peripheral blood had a normal 46,XY karyotype. The origin of the
      duplicated part of 3q was proved by fluorescence in situ hybridization (FISH)
      with the pHSR(sat III 15p) DNA probe and a chromosome 3-specific DNA library
      (i.e., chromosome painting). The chromosome finding in our case provides further
      proof of the close relationship between the rearrangement in region 3q13-->3q26
      and the pathogenesis of acute myeloid leukemia (AML). Our patient has transformed
      into erythroleukemia [M6 according to the French-American-British (FAB)
      classification] during the course of the disease.

PMID- 8275455
TI  - The application of fluorescent in situ hybridization to detect Mbcr/abl fusion in
      variant Ph chromosomes in CML and ALL.
AB  - We investigated the usefulness of fluorescent in situ hybridization with
      different-colored major breakpoint cluster region (Mbcr) and Abelson oncogene
      (abl) probes in clinical practice. In standard Ph chromosomes with a Mbcr
      breakpoint, these probes produced a fusion of Mbcr and abl signals that was
      visible in interphase and metaphase cells. The normal range for apparent Mbcr/abl
      fusion signals in interphase nuclei was established in bone marrow from 25 normal
      controls. We tested the probes on 35 bone marrow specimens from five normal
      subjects and 29 patients with various kinds of Ph chromosomes and chronic
      myelogenous leukemia or acute lymphocytic leukemia. This method produced Mbcr/abl
      fusion signals in patients with a standard Ph chromosome, simple or complex
      variants of Ph chromosomes, and "Ph-negative chronic myelogenous leukemia." In
      metaphase cells of patients with acute lymphocytic leukemia, this method
      established Ph chromosomes with minor bcr (mbcr) breakpoints. Fluorescent in situ
      hybridization is a relatively inexpensive and rapid method. When this method is
      used in conjunction with conventional chromosome analysis, the cytogeneticist can
      combine the power of complete karyotype studies and the resolution of molecular
      techniques for patients suspected of having a Ph chromosome.

PMID- 8275456
TI  - Trisomy 4 in a case of acute myelogenous leukemia accompanied by subcutaneous
      soft tissue tumors. Report of a case and review of the literature.
AB  - We report a patient with acute myelogenous leukemia [AML, French-American-British
      classification (FAB) M2] with trisomy 4, who developed subcutaneous soft tissue
      tumors at the time leukemia was diagnosed. A review of the literature on AML with
      trisomy 4 suggests a relation between trisomy 4 and tumor formation of leukemic
      cells.

PMID- 8275458
TI  - Comparison of clinical and biologic features between myeloid and lymphoid
      transformation of Philadelphia chromosome positive chronic myeloid leukemia.
AB  - Analysis of clinical and biologic features of chronic myeloid leukemia (CML) in
      blast crisis (BC) was performed on 36 patients: 25 had myeloid and 11 had
      lymphoid transformation. The median duration from diagnosis to onset of BC was
      significantly shorter in patients with lymphoid BC (6 months) than in those with
      myeloid BC (41 months). Patients in lymphoid transformation showed better
      response to therapy and had a significantly longer median survival time after BC
      than patients with myeloid transformation (56% vs 0% and 10 months vs 4 months,
      respectively). The leukemic cells from all the patients with lymphoid BC showed B
      cell immunophenotype, confirmed by the presence of immunoglobulin (Ig) heavy
      chain gene rearrangements in the five patients studied. Two of the eight patients
      with complete marker study expressed myeloid-associated antigens on the blasts. A
      high incidence of CD7 expression (7/17 or 41%) was found in patients with myeloid
      BC, but none of the patients who had DNA analysis showed rearrangement of T-cell
      receptor beta chain gene. Chromosomal abnormalities +8, +19, +21, and i(17q) were
      detected only in the patients with myeloid BC but not in those with lymphoid BC.
      Combined analysis of the patients in this series and those reported previously
      has revealed a statistically significant difference in the distribution of bcr
      breakpoints between myeloid and lymphoid BC: the bcr breakpoints in more than
      half of the patients with myeloid crisis were mapped to Zone 2 while those in
      patients with lymphoid crisis occurred most frequently in Zone 3.

PMID- 8275457
TI  - Cytogenetic studies of epithelial ovarian carcinoma.
AB  - We performed cytogenetic studies of 36 human epithelial ovarian carcinomas using
      in situ culture and robotic harvest. We obtained analyzable metaphases of all 36
      tumors (100%). One or more chromosomally abnormal clones were observed in 80% of
      tumors. Common clonal chromosome gains (each occurring in six or more cases)
      included +1, +2, +3, +6, +7, +9, and +12. Common clonal chromosome losses
      (occurring in 12 or more cases) included -X, -4, -8, -11, -13, -15, -17, and -22.
      Common clonal structural abnormalities (occurring in four or more cases) involved
      regions 1p36, 1q32, 1q42, 3p13-->p26, 3q26-->q29, 7p22, 9q34, 11p13-p15, 17q21-
      >q23, 19p13.3, and 19q13.3. Trisomy 12 was noted as the sole anomaly in three of
      five borderline and grade 1 tumors. Two grade 2 tumors contained i(1q), -14, -15
      and -22. The results suggest that the pathogenesis of borderline and low-grade
      tumors may differ from that of higher grade tumors. Two high-grade tumors had an
      apparent translocation between 17q21 and 19p13.3, two chromosome regions believed
      to be critical to ovarian carcinogenesis.

PMID- 8275459
TI  - Translocation (12;13) in a case of infantile fibrosarcoma.
AB  - Cytogenetic analysis of an infantile fibrosarcoma showed the presence of a
      t(12;13) and numerical changes of chromosomes 15 and 20. Until now only non
      random gain or loss of total chromosomes as well as one case with a deletion at
      17p have been reported for this kind of tumor. This report represents the first
      cytogenetic description of an aggressive infantile fibrosarcoma with a
      translocation.

PMID- 8275460
TI  - Concordance between karyotyping and in situ hybridization procedures in the
      detection of monosomy 9 in bladder cancer.
AB  - Twenty-three cases of transitional cell carcinoma (TCC) with a diploid model
      chromosome count as selected after karyotyping were analyzed by fluorescence in
      situ hybridization (FISH), using a probe for the heterochromatic region of
      chromosome 9. A monosomy for chromosome 9 was detected in 50% by karyotyping and
      after FISH in 52% of the cases. A full concordance between FISH and conventional
      karyotyping was found. We concluded that FISH can be reliably applied to
      interphase nuclei of TCC for the detection of numerical chromosome 9 aberrations.

PMID- 8275461
TI  - Activation of p53 gene expression in premalignant lesions during head and neck
      tumorigenesis.
AB  - With the goal of identifying a potential intermediate biomarker in the multistep
      process of head and neck cancer development, we conducted immunohistochemical
      analyses for p53 expression in 33 patients with head and neck squamous cell
      carcinomas whose tissue sections contained adjacent normal epithelium,
      hyperplastic, and/or dysplastic lesions. Fifteen of 33 (45%) squamous cell
      carcinomas of the head and neck expressed p53, but none of four normal control
      patients (cancer-free nonsmokers) expressed detectable p53 in oral mucosa
      specimens. To determine when p53 expression is initiated during head and neck
      tumorigenesis, we examined the normal and premalignant lesions adjacent to the
      tumors. Five of 24 (21%) samples of normal epithelium adjacent to tumors, 7 of 24
      (29%) samples of hyperplasia, and 9 of 20 (45%) samples of dysplasia expressed
      p53. Quantitative image analysis demonstrated not only a gradual increase in the
      amount of p53 expression as tissue abnormalities progressed but also a
      topological change in expression. Whereas p53 expression, when present, was
      limited to the basal layer in normal epithelium adjacent to tumor, the expression
      of p53 expanded into the parabasal and superficial layers in hyperplasia and
      dysplasia. We conclude that p53 expression can be altered in very early phases of
      head and neck tumorigenesis. Thus, it may be an excellent candidate for risk
      assessment and may serve as an intermediate biomarker in chemoprevention trials.

PMID- 8275462
TI  - Inhibition of human O6-methylguanine-DNA methyltransferase by 5-methylcytosine.
AB  - The ability of cloned human O6-methylguanine-DNA methyltransferase to repair a
      methylated guanine in a CpG-containing sequence, i.e., island, was studied by
      using a synthetic double-stranded 20-mer oligonucleotide from codon 248 of the
      p53 gene and another designed sequence. The double-stranded oligonucleotides
      incorporating 5-methylcytosine (5mC) and O6-methylguanine (O6mG) in various
      combinations in a CpG site were 5' labeled with 32P and incubated with
      recombinant O6-methylguanine-DNA methyltransferase. The rate constant for O6
      methylguanine-DNA methyltransferase repair of O6mG in this oligomer was always
      higher with the substrate which contained only the O6mG, as compared to the
      oligomer that included a 5mC adjacent in the 5'-position to the methylated
      guanine. The reduction in substrate activity ranged from 75% (modified p53
      sequence) to 100% (in the designed oligomer). A 5mC opposite the O6mG reduced the
      rate slightly. These results suggest that O6-methylation of the guanine moiety at
      CpG islands may not be efficiently repaired when normal 5mC is present and this
      may contribute significantly to an increase in mutagenesis of p53 and like
      molecules.

PMID- 8275463
TI  - Isolation and identification of fresh tumor-derived endothelial cells from a
      murine RIF-1 fibrosarcoma.
AB  - Tumor vasculature is anatomically heterogeneous and distinct from the vasculature
      found in normal mature tissues. Examination of the differences between tumor and
      normal vasculature is critical to the future design of therapeutic modalities
      which either target tumor vasculature or potentially enable more efficient
      delivery of tumor cytotoxic agents. Such efforts to date have been hampered due
      to the inability to isolate live endothelial cells from solid tumors. We report
      here the isolation of fresh, noncultured endothelial cells from a C3H/HeJ RIF-1
      murine fibrosarcoma through the use of fluorescence-activated cell sorting based
      on antibody staining for angiotensin-converting enzyme with further
      characterization by uptake and metabolism of acetylated low-density lipoprotein,
      factor VIII staining, and electron microscopy.

PMID- 8275464
TI  - Evidence for the existence of a third progesterone receptor protein in human
      breast cancer cell line T47D.
AB  - We have used a new monoclonal antibody, designated C-262, directed against the
      last 14 amino acids of the carboxy-terminus of human progesterone receptors (N.L.
      Weigel et al., Mol. Endocrinol., 6: 1585-1597, 1992) to analyze progesterone
      receptor structure. This new antibody recognizes the previously described B
      receptors (M(r) 120,000) and the naturally occurring N-terminal truncated A
      receptor (M(r) 94,000). In addition to B- and A-receptors, C-262 detects a third
      progestin-binding protein with a molecular weight of approximately 60,000 in the
      progestin-responsive human breast cancer cell line, T47D. The 60,000 dalton
      protein is predominantly found in the cytosolic fraction of untreated T47D cells
      and binds tightly to the nucleus following progesterone or R5020 treatment of
      T47D cells. These dynamics are similar to the previously described progesterone
      receptor isoforms. The 60,000 dalton protein binds the synthetic progestin,
      [3H]R5020, which competes with cold R5020 as determined with the technique of in
      situ photoaffinity labeling. Prolonged incubation of nuclear extracts at elevated
      temperatures does not result in accumulation of the 60,000 dalton protein, yet
      the level of photoaffinity-labeled B- and A-receptors declines. These data
      support our hypothesis that the 60,000 dalton protein is not a degradation
      product of the two larger progesterone receptor isoforms but a distinct progestin
      binding protein. This is further supported by our previous study identifying at
      least two progesterone receptor mRNAs that do not code B- or A-receptors. These
      two transcripts are not unique to T47D cells and also are present in human breast
      cancer cells, MCF-7, and normal human endometrium. Taken together, these data
      provide evidence for the existence of a third progesterone receptor isoform in
      progestin-responsive tissues.

PMID- 8275465
TI  - Distinct deletions of chromosome 9p associated with melanoma versus glioma, lung
      cancer, and leukemia.
AB  - Deletions of DNA on chromosome 9p21-22 are frequently observed in cells derived
      from melanomas, gliomas, non-small cell lung cancers, and acute lymphoblastic
      leukemia. The minimal deletion shared by the latter three cancers extends from
      the interferon-alpha locus towards the centromere; its centromeric end is flanked
      by the gene encoding methylthioadenosine phosphorylase. We have determined that
      the telomeric end of the minimal homozygous deletion shared by two melanoma cell
      lines does not include the methylthioadenosine phosphorylase locus. Thus, a
      distinct region of DNA is lost in melanoma. The physical size of this region
      remains to be defined precisely, but it may extend over several million base
      pairs.

PMID- 8275466
TI  - Estrogen receptor mutations in tamoxifen-resistant breast cancer.
AB  - Clinical resistance to antiestrogens like tamoxifen is a major problem in the
      treatment of hormone-dependent breast cancers. Since the estrogen receptor plays
      a central role in mediating the effects of estrogens and antiestrogens, we
      hypothesized that mutations in the estrogen receptor could be one mechanism by
      which breast tumors evolve from a hormone-dependent to a hormone-independent
      phenotype. The eight exons of the estrogen receptor complementary DNA from 20
      tamoxifen-resistant and 20 tamoxifen-sensitive tumors were screened by Single
      Strand Conformation Polymorphism (SSCP), and the variant conformers were
      sequenced to identify the nucleotide changes. A 42-base pair replacement was
      found in exon 6 of a tamoxifen-resistant tumor. A single base pair deletion in
      exon 6 of a tamoxifen-resistant metastatic tumor but not in the primary tumor was
      detected in another case. If translated, both these mutations could generate
      truncated receptors with an intact DNA-binding domain and a defective hormone
      binding domain that could constitutively activate transcription of previously
      estrogen-responsive genes. The remaining 18 of 20 tamoxifen-resistant tumors did
      not contain mutations in any of the 8 exons of the estrogen receptor
      complementary DNA. These results suggest that mutations in the estrogen receptor
      occur at a low frequency and do not account for most estrogen-independent,
      tamoxifen-resistant breast tumors.

PMID- 8275467
TI  - Expression of the neuroectodermal intermediate filament nestin in human
      melanomas.
AB  - Nestin is a newly identified intermediate filament expressed in proliferating
      neuronal progenitor cells, but not in the adult brain. Nestin expression
      reappears in many tumors of the central nervous system and has in human
      glioblastomas been associated with a high degree of malignancy. Because
      melanocytes are of neuroectodermal origin, we studied nestin expression in benign
      and malignant cells of the melanocytic lineage using Northern blot and
      immunohistochemical analyses. Nestin mRNA was detected in 24 of 34 metastatic
      melanomas and in 1 of 4 benign nevi, whereas the protein was expressed in 10 of
      15 primary melanomas, in 29 of 34 metastatic tumors, and in 3 of 4 nevi. Neither
      normal melanocytes nor any of 4 basal cell carcinomas showed detectable levels of
      the protein. The high fraction of melanocytic tumors which express nestin,
      particularly the metastatic melanomas, suggests that nestin may be a useful
      marker for such malignancies. Furthermore, although no significant correlation
      between nestin expression and tumor malignancy was observed, the protein was most
      abundantly expressed in the infiltrating part of the tumors, indicating a
      possible involvement of nestin in tumor invasion.

PMID- 8275468
TI  - Overexpression of multidrug resistance-associated protein (MRP) increases
      resistance to natural product drugs.
AB  - Amplification of the gene encoding multidrug resistance-associated protein (MRP)
      and overexpression of its cognate mRNA have been detected in multidrug-resistant
      cell lines derived from several different tumor types. To establish whether or
      not the increase in MRP is responsible for drug resistance in these cell lines,
      we have transfected HeLa cells with MRP expression vectors. The transfectants
      display an increase in resistance to doxorubicin that is proportional to the
      levels of a M(r) 190,000, integral membrane protein recognized by anti-MRP
      antibodies. The transfectants are also resistant to vincristine and VP-16 but not
      to cisplatin. The results demonstrate that MRP overexpression confers a multidrug
      resistance phenotype similar to that formerly associated exclusively with
      elevated levels of P-glycoprotein.

PMID- 8275469
TI  - Percentage of embryonal carcinoma and of vascular invasion predicts pathological
      stage in clinical stage I nonseminomatous testicular cancer.
AB  - We analyzed 92 clinical stage I nonseminomatous testicular germ cell tumors for
      primary tumor histological factors that would distinguish true pathological stage
      I disease (N = 54) from those patients who harbored occult disease and actually
      were later found to have pathological stage II disease (N = 38). Primary tumor
      pathological material was analyzed for vascular invasion, lymphatic invasion,
      tunical invasion, and quantitative determination of percentage of the primary
      tumor composed of embryonal carcinoma, yolk sac carcinoma, teratoma, and
      seminoma. Univariate logistic regression analyses revealed that vascular invasion
      (P = 0.0001), percentage of embryonal carcinoma (P = 0.0001), lymphatic invasion
      (P = 0.0001), and tunical invasion (P = 0.0013) were higher in pathological stage
      II and that percentage of teratoma (P = 0.0001) and of yolk sac carcinoma (P =
      0.0174) were higher in stage I. Percentage of seminoma was not significant.
      Individually, these parameters were able to correctly predict occult disease 66.3
      to 80.4% of the time. In multivariate logistic regression analysis, only vascular
      invasion and percentage of embryonal carcinoma remained significant, and a model
      using these two variables was able to correctly predict stage 85.9% of the time.
      Vascular invasion and determination of percentage of embryonal carcinoma should
      be assessed for all clinical stage I nonseminomatous germ cell tumor patients and
      the model presented herein can be used clinically to predict the likelihood of
      occult disease and dictate therapy.

PMID- 8275470
TI  - Fetal isoform of human retinoic acid receptor beta expressed in small cell lung
      cancer lines.
AB  - The retinoic acid receptor type beta (RAR beta) complementary DNA from a small
      cell tumor line was amplified, sequenced, and found to be homologous to the
      murine RAR beta 1. Seventeen lung tumor lines were analyzed. Five of seven small
      cell lung carcinoma lines expressed RAR beta 1, but only one other line
      (epidermoid) expressed the isoform, and this was at trace levels. Two other
      epidermoid lines, as well as three adenocarcinoma, two adenosquamous, and two
      large cell-derived lines did not express RAR beta 1. Nine adult human tissues,
      including lung, were analyzed, and in contrast to what has been reported for the
      mouse, undetectable or barely detectable levels were observed. On the other hand,
      a total of 13 different fetal tissues, at three different developmental stages,
      all expressed RAR beta 1. RAR beta 1 may be a master developmental gene in
      humans, and the remarkably specific association with small cell lung carcinoma
      suggests a molecular link between this type of cancer and development.

PMID- 8275471
TI  - Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without
      cytogenetic evidence of 11q23 chromosomal translocations.
AB  - Translocations which involve chromosome band 11q23 are frequently found in
      infants and adults with acute myeloid leukemia (AML) or acute lymphoblastic
      leukemia. We previously cloned a gene called ALL-1 which spans the 11q23
      breakpoint and is rearranged in most cases of leukemia with 11q23 abnormalities.
      In the present report, we have investigated the occurrence of ALL-1 rearrangement
      in cases of AML without cytogenetic evidence of 11q23 abnormalities. We detected
      molecular rearrangements of the ALL-1 gene in 3 of 4 patients with de novo AML
      and trisomy 11 as a sole chromosomal abnormality. Furthermore, we found DNA
      rearrangements of ALL-1 in 2 of 19 patients with de novo AML and normal
      cytogenetics. We conclude that molecular rearrangement of ALL-1 often can be
      detected in de novo AML, despite the absence of cytogenetic abnormalities
      involving 11q23.

PMID- 8275472
TI  - Ultraviolet radiation induces phosphorylation of the epidermal growth factor
      receptor.
AB  - Ultraviolet light in solar radiation is responsible for more than 600,000
      malignancies each year in the United States alone, making it the most efficient
      environmental carcinogen known. Ultraviolet radiation-induced direct DNA damage
      is thought to be responsible for its initiating properties, while the promotional
      aspects of such radiation are poorly defined and only recently gaining attention.
      We show here for the first time that physiologically relevant doses of
      ultraviolet radiation induce phosphorylation of the epidermal growth factor
      receptor in A431 keratinocytes at tyrosine sites within 30 min. Such alteration
      of this major signal transduction system is probably an important step in the
      ultraviolet radiation-induced, epidermal cell-signalling cascade.

PMID- 8275473
TI  - Messenger RNA levels of five genes located at chromosome 11q13 in B-cell tumors
      with chromosome translocation t(11;14)(q13;q32).
AB  - To identify genes activated by chromosome translocation t(11;14)(q13;q32), mRNA
      levels of five genes (cyclin D1, EXP1, MB38, HST1, and INT2) at chromosome 11q13
      were investigated. The cyclin D1 mRNA increased in BCL-1-rearranged B-cell tumor
      cell lines SP-49, NOP-2, FLAM-76, KMS-12-PE, and KMS-12-BM cells, while it was
      not detected in cell lines without the translocation, Raji, U266, and HEL cells.
      A significant amount of the MB38 mRNA was detected irrelevantly to the
      translocation in all of these cell lines. The mRNAs of EXP1, HST1, and INT2 were
      undetectable in these cells. The results suggested that the translocation
      activates cyclin D1 alone, while the mRNA levels of the other four genes are
      regulated independently of the translocation.

PMID- 8275474
TI  - Transforming growth factor beta-treated normal fibroblasts eliminate transformed
      fibroblasts by induction of apoptosis.
AB  - Transforming growth factor beta (TGF-beta) induces normal fibroblasts to perform
      an inhibitory effect directed against transformed cells (P. Hofler, I. Wehrle,
      and G. Bauer, Int. J. Cancer, 54: 125-130, 1993). Coculture of normal fibroblasts
      with transformed cells, either resistant to G 418 or expressing Mx antigen
      detectable by specific immunofluorescence, allowed discrimination between three
      theoretical mechanisms of inhibition: irreversible inhibition of proliferation;
      reversion to the nontransformed phenotype; or elimination of transformed cells.
      Our data demonstrate that normal fibroblasts treated with TGF-beta are able to
      eliminate transformed cells by induction of apoptosis. Sensitivity against TGF
      beta-induced elimination seems to be a general feature of in vitro-transformed
      cell lines. TGF-beta-induced elimination of transformed fibroblasts by their
      untransformed counterparts is proposed as a potential potent control point in
      carcinogenesis, which may lead to the suppression of transformed cells.

PMID- 8275475
TI  - Abnormal bone marrow B-cell differentiation in pre-B lymphoma-prone SL/Kh mice.
AB  - SL/Kh mice spontaneously develop pre-B lymphomas with surface phenotypes of
      B220+, BP-1+, Thy-1-, and surface immunoglobulin negative. The immunoglobulin
      heavy chain of lymphoma is clonally rearranged but the light chain gene remains
      in germline configuration. Studying prelymphoma stage SL/Kh bone marrow (BM), we
      found unusual multiclonal expansion of BP-1+ pre-B cells [34.8 +/- 5.8% (mean +/-
      SD)] by 4 weeks of age, whereas there were far fewer of such cells in most other
      laboratory strains (8 +/- 5%). The BP-1+ cells did not express surface
      immunoglobulin, Thy-1.1, or c-kit. Therefore, they seemed to belong to the pre-B
      II category. Increased numbers of BP-1+ cells were seen in F1 hybrids between
      SL/Kh and NFS/N; thus it was apparently a dominant heritable property of SL/Kh
      mice. Emergence of this population was independent of expression of endogenous
      ecotropic virus, since they were present in BMs of the F1 hybrid to C4W (Fv-4')
      and were not inhibited by neonatal injection of maternal resistance factor. In
      the radiation chimeras SL/Kh-->BALB/c, BP-1+ cells appeared abundantly (29.0 +/-
      3.8%), whereas in the reciprocal chimeras BALB/c-->SL/Kh, for fewer (5.5 +/-
      2.3%) appeared. Therefore, expansion of BP-1+ cells in prelymphomatous BM is a
      property of SL/Kh stem cells rather than BM microenvironments.

PMID- 8275476
TI  - Genetic predisposition to pre-B lymphomas in SL/Kh strain mice.
AB  - Genetic predisposition of SL/Kh mice to spontaneous pre-B lymphomas was
      investigated in crosses between SL/Kh and NFS/N, another inbred strain of mice
      lacking endogenous ecotropic provirus and spontaneous lymphoma. (SL/Kh x NFS/N)
      F1 hybrids developed lymphomas similar to those in SL/Kh but at a lower frequency
      and with a longer latent period. Of 83 backcross mice to NFS/N, 22 developed
      hemopoietic tumors: 8 were diffuse lymphoblastic lymphomas; 2 were myeloid
      leukemias arising by 12 months of age; and 12 were follicular center cell
      lymphomas found later in life. Of 6 endogenous ecotropic proviruses in SL/Kh, 2
      were expressed in (SL/Kh x NFS) F1 backcrossed to NFS. One, encoded by a 27
      kilobase EcoRI fragment, was closely linked to Gpi-1a on chromosome 7 and its
      expression seemed to be a prerequisite for the occurrence of all types of
      hemopoietic tumors. Microsatellite analysis of the backcross generation revealed
      multiple host genetic factors determining susceptibility to tumors. An allele
      derived from SL/Kh, mapped in the major histocompatibility locus on chromosome
      17, was essential for development of early onset tumors. This locus was
      designated as Esl-1 (early lymphoma of SL-1). On the other hand, follicular
      center cell lymphomas developed mostly in the backcross mice homozygous for the
      NFS/N derived allele at the D4MIT17-linked locus, designated as foc-1 (follicular
      center cell lymphoma-1), on chromosome 4.

PMID- 8275477
TI  - Investigation of a new pure antiestrogen (ICI 182780) in women with primary
      breast cancer.
AB  - We have conducted a clinical trial of a novel pure antiestrogen, 7 alpha-[9
      (4,4,5,5,5-pentafluoropentylsulfinyl)nonyl]estra-1,3,5,(1 0)-triene-3,17 beta
      diol (ICI 182780), to assess its tolerance, pharmacokinetics, and short term
      biological effects in women with primary breast cancer. Fifty-six patients were
      randomized to either a control group (n = 19), in which they received no
      preoperative treatment, or a treatment group (n = 37), in which they received
      daily i.m. injections of ICI 182780 at doses of 6 mg (n = 21) or 18 mg (n = 16)
      for 7 days prior to primary breast surgery. Serum drug concentrations,
      gonadotropin levels, and sex hormone-binding globulin levels were measured during
      the study period by radioimmunoassay. Expression of estrogen receptors (ER),
      progesterone receptors, the estrogen-induced protein pS2, and the cell
      proliferation-related antigen Ki67 was determined immunocytochemically in pre-
      and poststudy tumor samples. Treatment with ICI 182780 caused no serious drug
      related adverse events and had no effect on serum gonadotropin or sex hormone
      binding globulin levels. Minor adverse events occurred in 5 patients receiving
      the 6-mg dose and 3 patients receiving the 18-mg dose. The serum concentration of
      ICI 182780 was dose dependent but showed variation between individuals. There was
      evidence of an approximately 3-fold drug accumulation over the short treatment
      period but steady state levels were not reached by the end of the 7 days. In
      patients with ER-positive tumors, treatment with ICI 182780 was associated with
      significant reductions in the tumor expression of ER (median ER index, 0.72
      before versus 0.02 after treatment; P < 0.001), progesterone receptor (median
      progesterone receptor index, 0.50 before versus 0.01 after treatment; P < 0.05),
      and Ki67 (median Ki67 labeling index, 3.2 before versus 1.1 after treatment; P <
      0.05). Treatment with ICI 182780 also resulted in a significant reduction in pS2
      expression (P < 0.05) but this appeared unrelated to tumor ER status. In
      conclusion, ICI 182780 was well tolerated after short term administration and
      produced demonstrable antiestrogenic effects in human breast tumors in vivo,
      without showing evidence of agonist activity. These properties identify ICI
      182780 as a candidate agent with which to evaluate whether a pure estrogen
      antagonist offers any additional benefit in the treatment of human breast cancer
      over conventional nonsteroidal antiestrogens, typified by tamoxifen, which
      exhibit variable degrees of agonist activity.

PMID- 8275478
TI  - Kinetics of the immune response and regression of metastatic lesions following
      development of humoral anti-high molecular weight-melanoma associated antigen
      immunity in three patients with advanced malignant melanoma immunized with mouse
      antiidiotypic monoclonal antibody MK2-23.
AB  - Active specific immunotherapy has been implemented in patients with advanced
      malignant melanoma, utilizing the mouse antiidiotypic (anti-id) monoclonal
      antibody (mAb) MK2-23 which bears the internal image of high molecular weight
      melanoma associated antigen (HMW-MAA). In a previous study, development of anti
      HMW-MAA immunity in patients with advanced malignant melanoma immunized with anti
      id mAb MK2-23 was found to be associated with a statistically significant
      survival prolongation. Since no information is available about the relationship
      between development of immunity and clinical response in patients immunized with
      anti-id mAb, the present study has characterized the kinetics of the immune
      response in three patients with advanced malignant melanoma who experienced
      regression of metastatic lesions following immunization with the anti-id mAb MK2
      23. The three patients developed anti-mouse IgG antibodies, anti-anti-id
      antibodies and anti-HMW-MAA antibodies. The anti-HMW-MAA antibodies are mainly
      IgG, suggesting that the immune response elicited by anti-id mAb MK2-23 is T-cell
      dependent. The development of anti-HMW-MAA immunity preceded the reduction in the
      size of metastatic lesions. This temporal relationship suggests but does not
      prove that the anti-HMW-MAA immunity elicited by anti-id mAb MK2-23 has a
      beneficial effect on the clinical course of the disease in patients with
      malignant melanoma. This finding in conjunction with minor side effects
      associated with repeated administrations of mouse anti-id mAb MK2-23 suggest that
      active specific immunotherapy with anti-id mAb which bear the internal image of
      melanoma-associated antigen represents a viable therapeutic approach to malignant
      melanoma.

PMID- 8275479
TI  - Phase I and pharmacological study of the novel topoisomerase I inhibitor 7-ethyl
      10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) administered
      as a ninety-minute infusion every 3 weeks.
AB  - 7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11;
      Irinotecan), a semisynthetic analogue of camptothecin (CPT) with broad
      preclinical antitumor activity, has demonstrated impressive activity in phase II
      trials in Japan in advanced small and non-small cell lung, colorectal, cervical,
      and ovarian carcinomas, as well as in refractory lymphomas and leukemias. In this
      phase I and pharmacological study, 90-min infusions of CPT-11 were administered
      every 3 weeks at doses ranging from 100 to 345 mg/m2 to patients with solid
      malignancies. Acute, severe, and refractory vomiting, diarrhea, and/or abdominal
      cramps associated with flushing, warmth, and diaphoresis occurred in the
      immediate posttreatment period at the 240-mg/m2 dose level in several patients
      who were not treated with premedications. The characteristics and temporal nature
      of these toxicities, the prompt resolution of symptoms following treatment with
      diphenhydramine, and the successful use of a premedication regimen consisting of
      ondansetron and diphenhydramine in preventing these acute effects suggest that
      vasoactive substances are involved in the mediation of these acute toxicities.
      With the routine use of these premedications, there was no single toxicity type
      that limited the escalation of CPT-11 doses. Instead, a constellation of severe
      hematological and gastrointestinal effects precluded the repetitive
      administration of CPT-11 at doses above 240 mg/m2, the maximum tolerated dose and
      recommended phase II dose on this schedule. Major responses were observed in
      patients with advanced colorectal, cervical, and renal cancers. The disposition
      of total CPT-11 in plasma was fit by a biexponential kinetic model with renal
      elimination accounting for 37 +/- 4% (SE) of total drug disposition. The Cmax for
      the active metabolite of CPT-11, 7-ethyl-10-hydroxycamptothecin (SN-38), was
      achieved at 2.2 +/- 0.1 h after treatment, and mean residence times for both CPT
      11 and SN-38 were long, 9.1 and 10.0 h, respectively. Compared with topotecan,
      another CPT analogue under development, a larger proportion of total drug
      exposure was accounted for by the active lactone (closed-ring) forms of CPT-11
      and SN-38; areas under the time-versus concentration curve for their respective
      lactone were 44 and 50% of areas under the time-versus-concentration curve for
      total CPT-11 and SN-38. Although intermittent dosing schedules appear to be
      superior to single dosing schedules for CPT and some CPT analogues in preclinical
      tumor models, the maintenance of biologically relevant concentrations of SN-38
      for relatively long durations may negate the potential pharmacological benefits
      of intermittent and continuous administration schedules for CPT-11.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8275480
TI  - DNA repair related to multiple skin cancers and drug use.
AB  - Defective repair of sunlight-induced DNA photodamage, coupled with an unusually
      high occurrence of multiple primary basal cell carcinomas (BCCs), is the major
      characteristic of xeroderma pigmentosum. Our recent work has indicated that this
      etiological paradigm may apply to skin cancer patients without an apparent
      hereditary disease. The present study reports on an investigation of whether
      medications such as photosensitizing drugs (antibiotics, corticosteroids, and
      aspirin) modulate skin cancer risk through alterations in DNA repair capacity
      (DRC). Using a new DNA repair (host cell reactivation) assay with peripheral T
      lymphocytes, we tested DRCs of 88 Caucasian BCC patients and 135 cancer-free
      controls. Subjects were between 20 and 60 years of age and free of known
      hereditary skin diseases. The age-adjusted means of DRC were calculated to
      compare repair levels associated with the use of specific drugs and hormones.
      Multiple linear regression models were used to correlate DRC with the number of
      skin cancers. The estimated odds ratio was used to describe the risk of BCCs. The
      distribution of DRCs of subjects was approximately normal, with a 5-fold
      variation between individuals. DRCs below the upper 30th percentile of controls
      were associated with an estimated 2.3-fold (95% confidence interval, 1.17-4.54
      fold) increased risk for the occurrence of BCCs. The lower the DRC was, the
      greater the number of skin tumors in individuals (P < 0.05), after adjustment for
      age. Although supplemental vitamin use was associated with reduced risk of skin
      cancer, it was not associated with differences in subjects' DRCs. However,
      individuals who reported taking either tetracycline or estrogen, two
      photosensitizing drugs, had higher DRCs, compared with those who had not used
      these drugs. Low DRC or a family history of skin cancer increased the probability
      that patients who were overexposed to sunlight would have multiple BCCs. DNA
      repair levels may be influenced by the use of selected photosensitizing drugs and
      estrogen.

PMID- 8275481
TI  - The herbal medicine sho-saiko-to inhibits proliferation of cancer cell lines by
      inducing apoptosis and arrest at the G0/G1 phase.
AB  - Water-soluble ingredients of the herbal medicine sho-saiko-to dose-dependently
      inhibited the proliferation of a human hepatocellular carcinoma cell line (KIM-1)
      and a cholangiocarcinoma cell line (KMC-1). Fifty % effective doses on day 3 of
      exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/
      26.5 micrograms/ml for KMC-1. However, almost no suppressive effects were
      detected in normal human peripheral blood lymphocytes or normal rat hepatocytes.
      Sho-saiko-to suppressed the proliferation of the carcinoma cell lines
      significantly more strongly than did each of its major ingredients, i.e.,
      saikosaponin a, c, and d, ginsenoside Rb1 and Rg1, glycyrrhizin, baicalin,
      baicalein, and wogonin, or another herbal medicine, juzen-taiho-to (P < 0.05 or
      0.005). Because such ingredients are barely soluble in water, there could be
      synergistic or additive effects of the ingredients in sho-saiko-to.
      Morphological, DNA, and cell cycle analyses revealed two possible modes of action
      of sho-saiko-to to suppress the proliferation of carcinoma cells; (a) it induces
      apoptosis in the early period of exposure and (b) it induces arrest at the G0/G1
      phase in the late period of exposure.

PMID- 8275482
TI  - Rapid tumor imaging by active background reduction using biotin-bearing liposomes
      and avidin.
AB  - Tumor imaging with labeled liposomes is slow; although they reach the tumor
      quickly, their blood clearance is slow, and the high blood background hinders
      early imaging. We have developed a rapid tumor imaging technique based on the
      active removal of liposomes from the circulation by using the avidin-biotin
      system. 67Ga- or 111In-labeled liposomes with biotin molecules bound on the
      surface were administered to mice bearing sarcoma 180, and avidin was
      administered 2 h later. The strong affinity between biotin and avidin initiated
      the aggregation of liposomes, resulting in their rapid removal from the
      circulation by the reticuloendothelial system, and the blood level of
      radioactivity was dramatically reduced without any change of the tumor level.
      Consequently, the tumor:blood ratio reached 14-18 only 2.5 h after liposome
      injection. Increased accumulation in the liver was also observed. By this method,
      an acceptable tumor image could be obtained no more than 2 h after administration
      of labeled liposomes.

PMID- 8275483
TI  - Potentiation of radiation-induced regrowth delay in murine tumors by fludarabine.
AB  - Fludarabine (9-beta-D-arabinofuranosyl-2-fluoroadenine-5'-monophosphate), an
      adenine nucleoside analogue, has previously been shown to inhibit the repair of
      radiation-induced chromosome damage. Thus fludarabine may have therapeutic
      utility in combination with photon irradiation. The purpose of this study was to
      determine whether fludarabine could enhance radiation-induced murine tumor
      regrowth delay and to determine the most effective dose and schedule of the
      combination. A significant (P < 0.05) absolute regrowth delay enhancement was
      observed in three murine tumor models (SA-NH, a sarcoma; and MCA-K and MCA-4,
      mammary carcinomas) when fludarabine (800 mg/kg) was given 1 h prior to 25 Gy
      gamma-irradiation. While fludarabine enhanced radiation-induced tumor regrowth
      delay when given between -36 h and +6 h of radiation (SA-NH tumor), the greatest
      enhancement was observed when fludarabine was given at -24 h prior to irradiation
      (radiation dose modification factor of 1.82 at -24 h compared to 1.57 at -3 h
      prior to radiation). The degree of fludarabine enhancement (at -3 or -24 h) was
      dose dependent at doses above 200 mg/kg. When fludarabine and radiation were
      administered on a fractionated schedule (fludarabine given 3 h prior to radiation
      each day for 4 days), the dose modification factor increased to 2.14 (1.63 if the
      effect of fludarabine alone is subtracted). These results suggest that
      fludarabine enhances radiation-induced tumor regrowth delay in a more than
      additive fashion after both single and fractionated treatments, and the degree of
      enhancement is dependent on the sequence and timing of administration, the
      fludarabine dose, and the tumor type. Thus, fludarabine may have clinical
      potential as a radiation enhancer in the treatment of solid tumors.

PMID- 8275484
TI  - Combination versus single agent therapy in effecting complete therapeutic
      response in human bladder cancer: analysis of cisplatin and/or 5-fluorouracil in
      an in vivo survival model.
AB  - An in vivo study of cisplatin (CDDP) and 5-fluorouracil (5FU) cytotoxicity was
      performed using a multidose matrix with a human bladder transitional cell
      carcinoma xenograft tumor line (DU4284) tested by subrenal capsule assay in 154
      nude mice (NM-SRCA). Statistical analysis of initial growth inhibition at 20 days
      and host survival demonstrates therapeutic, cooperative interaction. Toxic doses
      of either CDDP or 5FU alone as well as low-dose combinations provided modest or
      no survival benefit. The single dose of CDDP (7 mg/kg) and of 5FU (100 mg/kg) was
      best (by analysis of efficacy and toxicity) of those tested and caused > 97%
      initial regression. While 94% of controls incurred tumor deaths by 225 days, 75%
      treated at this dose were tumor free and likely cured. Our conclusions were: (a)
      NM-SRCA human xenograft testing is excellent for rapid in vivo screening of
      promising treatment strategies to evaluate for efficacy at acceptable toxicity,
      but confirmation of true therapeutic impact should be sought by correlating
      initial growth inhibition with host survival; (b) enhanced survival seen only
      when CDDP/5FU are used together (versus either single agent) supports the value
      of pursuing histiotype-specific screening of potentially synergistic drug
      combinations; and (c) of clinical relevance, human transitional cell carcinoma is
      now identified as a histiotype in which a therapeutic, cooperative interaction
      between CDDP/5FU has been demonstrated in vivo.

PMID- 8275485
TI  - Activity of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin in sensitive and
      resistant L5178Y lymphoblasts in vitro.
AB  - An L5178Y murine lymphoblast cell line resistant to 3'-(3-cyano-4-morpholinyl)-3'
      deaminoadriamycin (MRA-CN), L5178Y/MRA-CN, was isolated and characterized.
      L5178Y/MRA-CN cells were 9.6-fold resistant to MRA-CN compared with parental
      cells. The resistant cell line also displayed 2-fold resistance to 3'-(4
      morpholinyl)-3'-deaminoadriamycin but was not cross-resistant to Adriamycin or
      chlorambucil. Uptake of MRA-CN was slightly reduced in the resistant cells
      compared to sensitive cells, but the distribution of the drug within the cells
      was unchanged. DNA interstrand cross-linking by MRA-CN was not significantly
      different in the sensitive and resistant cell lines, but MRA-CN was slightly less
      effective in inhibiting both DNA and RNA synthesis in L5178Y/MRA-CN cells
      compared with parental cells. NADPH cytochrome P-450 reductase activity was
      increased in L5178Y/MRA-CN cells compared to parental cells, while the activity
      of DT-diaphorase was decreased in the resistant cells. The levels of glutathione
      and glutathione S-transferase activity were increased in the resistant cells
      compared to sensitive cells; however, pretreatment of L5178Y/MRA-CN cells with
      buthionine sulfoximine to reduce the glutathione level did not reverse the
      resistance of these cells to MRA-CN. MRA-CN induced DNA fragmentation that was
      characteristic of apoptosis in both L5178Y and L5178Y/MRA-CN cells at equitoxic
      drug concentrations. However, apoptosis occurred more rapidly in L5178Y/MRA-CN
      cells compared with parental cells. Thus, MRA-CN induces apoptosis in L5178Y
      cells, and this effect may be important for the anti-tumor activity of this
      agent. In contrast, DNA interstrand cross-linking does not appear to be the
      primary mechanism responsible for the cytotoxicity of MRA-CN in these cells.

PMID- 8275486
TI  - Characterization of resistance mechanisms to cis-diamminedichloroplatinum(II) in
      three sublines of the CC531 colon adenocarcinoma cell line in vitro.
AB  - Cisplatin resistance was developed in sublines of the CC531 rat colon
      adenocarcinoma cell line by continued low level drug exposure. Two relatively
      stable lines were obtained (RL2 and RL4) which were 6- and 20-fold more resistant
      to cisplatin. In addition, a subline more sensitive than the parent line by a
      factor of 2 (RLS) was obtained by subculture from a treated tumor. Mechanisms of
      resistance to cisplatin were investigated in these four lines, with the aim of
      determining the relative contributions of different resistance mechanisms at
      various resistance levels. Drug accumulation linearly decreased with increasing
      drug resistance. A 20-fold resistance was associated with only a 5-fold decrease
      in accumulation, suggesting that other resistance mechanisms may be involved in
      the total degree of resistance. Intracellular glutathione, measured
      fluorometrically, also increased with increasing resistance, varying by a factor
      of 4 between the most and least resistant lines. Reduction of glutathione levels
      by buthionine sulfoximine to parent line levels increased sensitivity but the
      cells remained considerably more resistant than parent cells. Resistant lines
      cultured in the absence of drug became progressively more sensitive, without
      accompanying changes in total glutathione levels. DNA-drug adducts, the presumed
      toxic lesion, were measured immunocytochemically. Initial levels decreased with
      increasing platinum resistance, although not proportional to resistance (factor
      of 5 decrease for 20-fold resistance). Drug dose ratios for equal initial adducts
      were similar to dose ratios for equal drug accumulation, implying that
      intracellular concentrations solely determine DNA adduction and that differences
      in glutathione level had little influence on the proportion of drug which
      eventually formed adducts. After 48 h, a better correlation between remaining
      adducts and resistance was found (factor 12 less adducts for 20-fold resistance).
      This implies that repair of adducts was important in determining survival. These
      data indicate that decreased drug accumulation played a proportionally greater
      role in the moderately resistant cell line and that adduct repair played a
      progressively greater role in the highly resistant cell line.

PMID- 8275487
TI  - Negative regulation of histone H1 kinase expression by mimosine, a plant amino
      acid.
AB  - The plant amino acid mimosine has been shown to reversibly arrest mammalian cells
      in late G1 phase of the cell cycle. However, the underlying molecular mechanisms
      of this block are not as yet understood. Here we show that mimosine prevents the
      serum-stimulated synthesis and activation of histone H1 kinase, a crucial
      regulator of cell cycle progression. The same effect is observed in
      logarithmically growing primary cells as well as transformed cells.
      Concomitantly, hyperphosphorylation of the retinoblastoma tumor suppressor gene
      product is partially inhibited. These effects are fully reversible, because
      removal of mimosine restores histone H1 kinase activity and the cells resume
      growth. Because the activity of histone H1 kinase has been shown to be absolutely
      required for cell cycle progression, it is conceivable that the cytostatic effect
      of mimosine is due to its negative effects on synthesis and activity of this
      enzyme.

PMID- 8275488
TI  - Loss of heterozygosity and p53 gene mutations in breast cancer.
AB  - Immunopositivity for the p53 tumor suppressor gene product was evaluated in 133
      breast cancers and compared to loss of heterozygosity (LOH) at various
      chromosomal loci. The validity of p53 immunopositivity as an indicator for p53
      mutations was verified using two molecular assays of p53 mutations: single
      stranded conformational polymorphism (32 cases) and/or direct sequencing (14
      cases). Immunopositivity was highly specific for mutations, since all of 15
      strongly immunopositive tumors (> 10% of the cells are positive) and seven of
      nine cases with borderline immunopositivity had mutations by molecular analysis
      but were somewhat lower in sensitivity, p53 mutations being also detected in
      three of 23 (13%) immunonegative cases. LOH was measured at loci on the following
      chromosomes (1p,q; 2p; 3p; 7q; 11p,q; 13q; 16q; 17p; 18p,q; and 22q) by Southern
      blotting, polymerase chain reaction amplification of restriction fragment length
      polymorphisms, or repetitive cytidine and adenine stretches (CA repeats). There
      was no association between p53 mutations and one measure of genomic instability,
      namely, high incidence of overall LOH. In contrast, p53 mutations strongly
      associated with LOH at two specific loci, 3p24-26 (P < 0.001) and 7q31 (P <
      0.05). There was no association between p53 mutations and LOH at 17p (site of the
      p53 gene), suggesting that breast cancers often have only one defective allele of
      the p53 gene.

PMID- 8275489
TI  - Allele loss on chromosome 16q24.2-qter occurs frequently in breast cancers
      irrespectively of differences in phenotype and extent of spread.
AB  - Loss of heterozygosity on chromosomal arm 16q has been shown to be a frequent
      event in sporadic breast cancer and is suggested to be involved in cancer
      development through inactivation of a tumor-suppressor gene. To specify the
      commonly deleted region in which the unknown tumor-suppressor gene is located, a
      deletion map of chromosome 16 was constructed for 78 breast cancers, using 27
      polymorphic DNA markers. Loss of heterozygosity on chromosome 16q was detected in
      38 of the tumors. From the deletion map, the incidence of the loss of
      heterozygosity was deduced to be > or = 36% in the region distal to 16q12 and was
      most frequent in the 16q24.2-qter region. Then, association of the loss of
      heterozygosity in the 16q24.2-qter region with clinicopathological parameters of
      the tumors was examined for a total of 234 tumors, to reveal its biological
      significance in breast cancer development. The total incidence of loss of
      heterozygosity in the 16q24.2-qter region was 52% (118 of 225), and loss of
      heterozygosity was frequent irrespectively of the presence of invasion and
      metastasis, differences in clinical stage, tumor size, histological grade, or
      type, or amounts of estrogen receptor. Inactivation of an unknown tumor
      suppressor gene on 16q24.2-qter was thus suggested to be involved commonly in the
      genesis of sporadic breast cancer, irrespectively of the extent of tumor spread
      or grade of aggressiveness of the cancer cells. On the other hand, eight cases
      revealed loss of heterozygosity not at 16q24-qter but in more proximal regions.
      Therefore, it appears that multiple tumor-suppressor genes are located on
      chromosome 16q.

PMID- 8275490
TI  - Preferential expression of the third immunoglobulin-like domain of K-sam product
      provides keratinocyte growth factor-dependent growth in carcinoma cell lines.
AB  - Previously, we identified an amplified gene in a stomach cancer cell line, KATO
      III, and designated it K-sam. This gene was later found to be identical with a
      gene for a receptor tyrosine kinase, bek/FGFR2. One of the characteristics of the
      K-sam gene is structural diversity of its transcripts; K-sam complementary DNA
      (cDNA) cloned from human brain (K-sam-I) has a completely different sequence at
      the third extracellular immunoglobulin-like domain as compared to that of the K
      sam cDNA derived from KATO-III cells (K-sam-II). Recent study has revealed that
      this difference signifies a differential ligand affinity; the receptor encoded by
      the K-sam-I cDNA has a high affinity for basic fibroblast growth factor (bFGF),
      while the K-sam-II cDNA corresponds to a receptor with the high affinity for
      keratinocyte growth factor (KGF). Reverse transcription-polymerase chain reaction
      and RNA blot analysis showed that the K-sam-II-type transcript was present in
      carcinoma cell lines but not in any of the sarcoma cell lines examined. The K-sam
      I-type transcript was expressed in both carcinoma and sarcoma cell lines.
      Furthermore, KGF enhanced the DNA synthesis of the esophageal cancer cells, TE-1,
      in a dose-dependent manner, while the effect of bFGF was not substantial. In
      contrast, the glioblastoma cell line, A-172, that expressed the bFGF receptor
      showed a mitogenic response to bFGF but not to KGF. These data suggest that KGF
      is a growth factor used preferentially in cancer cells, and this preference is
      based on the presence of the K-sam-II-type receptor in carcinoma cells but not in
      sarcoma cells due to alternative splicing.

PMID- 8275491
TI  - Allelotype of human bladder cancer.
AB  - To identify common regions of deletion in human bladder tumors, we have screened
      83 cases of transitional cell carcinoma for loss of heterozygosity (LOH) on all
      autosomal chromosome arms. Seventy-two restriction fragment length polymorphism,
      variable number of tandem repeats, and minisatellite markers and 18
      microsatellite markers were used to obtain a minimum of 50% informative results
      for each chromosome arm. A mean of 29.6 informative results per patient was
      obtained from 39 chromosome arms studied, representing information for 76% of
      chromosome arms. The most frequent losses were apparent monosomies of chromosome
      9 (9p, 51%; 9q, 57%). Other frequent losses were on chromosomes 11p (32%), 17p
      (32%), 8p (23%), 4p (22%), and 13q (15%). LOH of 4p has not been reported
      previously in bladder carcinoma. The frequency of LOH on all other chromosome
      arms was < 12%. LOH on chromosome 8p showed a significant association with both
      high tumor grade and stage, and LOH on 13q showed a significant association with
      high tumor grade. Fractional allelic loss was calculated for all tumors and had a
      mean of 0.125 and a median of 0.110. A significant association was found between
      increased fractional allelic loss and higher tumor grade. An association was also
      found between LOH of chromosomes 8p and 9q and values for fractional allelic loss
      > or = the median value. No associations were found between LOH on different
      pairs of chromosome arms.

PMID- 8275493
TI  - Differential expression of heat shock proteins in pancreatic carcinoma.
AB  - In the present study we sought to determine by Northern blot analysis and mRNA in
      situ hybridization whether gene expression of heat shock proteins (HSPs) (HSP 89
      alpha, HSP 89 beta, HSP 70, and ubiquitin) is altered in pancreatic carcinoma,
      compared to control tissues (normal pancreas and chronic pancreatitis tissue).
      HSP 89 alpha was selectively overexpressed in pancreatic carcinoma, and tumor
      cells were shown to contain the largest amount of HSP 89 alpha mRNA. Steady state
      levels of HSP 70 mRNA were increased in pancreatic carcinoma (tumor and
      connective tissue cells) and in chronic pancreatitis (connective tissue cells and
      residues of exocrine acinar cells). HSP 89 beta and ubiquitin B were
      constitutively expressed at high levels in pancreatic tissue from all three
      groups; HSP 89 beta mRNA was found in cells of parenchymal and stromal origin. A
      strong correlation was found between the expression of HSP 70 and the expression
      of transforming growth factor beta 1. The finding that HSPs are differentially
      expressed in pancreatic cancer, compared to normal pancreas and chronic
      pancreatitis tissue, and the cancer specificity of HSP 89 alpha suggest that HSPs
      play a specific role in the pathogenesis of pancreatic cancer, e.g., by
      participating in regulatory processes or in tumor immunity, as proposed
      previously.

PMID- 8275492
TI  - Elevation of topoisomerase I messenger RNA, protein, and catalytic activity in
      human tumors: demonstration of tumor-type specificity and implications for cancer
      chemotherapy.
AB  - Topoisomerase I has been identified as an intracellular target of camptothecin, a
      plant alkaloid with anticancer activity. Various lines of evidence suggest that
      the sensitivity of cells to this drug is directly related to the topoisomerase I
      content. In humans, the levels of topoisomerase I have been shown to be elevated
      in colorectal tumors, compared to normal colon mucosa. The aim of our study was
      to determine whether (a) topoisomerase I levels are elevated in other solid
      tumors, (b) the elevated enzyme is catalytically active in these tumors, and (c)
      the increase in topoisomerase I levels in colorectal tumors is a result of
      increased transcription or translation. Topoisomerase I levels were quantitated
      in crude extracts from colorectal, prostate, and kidney tumors and their matched
      normal counterparts by Western blotting and by direct determination of catalytic
      activity, and mRNA levels were determined by Northern blotting. By Western
      blotting, colorectal tumors showed 5-35-fold increases in topoisomerase I levels,
      compared to their normal colon mucosa. In the case of prostate tumors, the
      increase was 2-10-fold, compared with benign hyperplastic prostate tissue from
      the same patients. However, no difference was observed in topoisomerase I levels
      in kidney tumors, compared to their normal counterparts. The catalytic activity
      of topoisomerase I was determined by a quantitative 32P-transfer assay in crude
      homogenates, without isolating nuclei. Colorectal and prostate tumors exhibited
      11-40- and 4-26-fold increases, respectively, in catalytic activity. However,
      kidney tumors did not show any alteration in catalytic activity, compared to
      their normal matched samples. Thus, for all three tumor types there was a good
      correlation between enzyme levels and catalytic activity. Finally, colorectal
      tumors were analyzed for steady state mRNA levels. A 2-33-fold increase in mRNA
      levels was found in colorectal tumors, compared to normal colon mucosa. These
      results suggest that alterations in topoisomerase I expression in humans are
      tumor type specific and that the increase in topoisomerase I levels results from
      either increased transcription of the topoisomerase I gene or increased mRNA
      stability.

PMID- 8275494
TI  - Analysis of the tumor suppressor activity of the K-rev-1 gene in human tumor cell
      lines.
AB  - Overexpression of the human K-rev-1 gene in v-Ki-ras-transformed NIH 3T3 cells
      has been reported to result in the reversal of transformation and tumor
      suppression. To address whether human K-rev-1 is a tumor suppressor gene of human
      tumor cells, we have systematically transfected epitope-tagged wild-type or
      activated mutant K-rev-1 complementary DNA expression vectors into a series human
      tumor cell lines that express an activated ras oncogene, namely HT1080, EJ, and
      SW480. Using the epitope-tag-specific monoclonal antibody, it is shown that the K
      rev-1 protein localizes to the medial/trans-Golgi network. Ectopic expression of
      the wild-type or activated mutant K-rev-1 protein did not significantly affect
      the morphology or in vitro growth of any clones. Furthermore, all clones
      expressing the wild-type or activated mutant K-rev-1 protein were tumorigenic.
      Western blot analysis of tumor reconstitutes demonstrated that there was no
      decrease or loss of introduced K-rev-1 protein expression. The results in the
      present study demonstrate that expression of K-rev-1 does not reverse the
      transformed phenotype or significantly affect the tumorigenic phenotype of human
      tumor cell lines that express endogenous ras oncogenes.

PMID- 8275495
TI  - Tumor cell-derived 12(S)-hydroxyeicosatetraenoic acid induces microvascular
      endothelial cell retraction.
AB  - Our previous work demonstrated that the 12-lipoxygenase metabolite of arachidonic
      acid, 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE] induced a nondestructive
      and reversible retraction of cultured endothelial cells. In the current study we
      tested the hypothesis that tumor cells produce 12(S)-HETE during their
      interactions with endothelial cells which in turn induces endothelial cell
      retraction. Coincubation of Lewis lung carcinoma cells or elutriated B16
      amelanotic melanoma (B16a) cells but not 3T3 fibroblasts with microvascular
      endothelial cells (CD3) resulted in a time- and concentration-dependent
      retraction of the CD3 monolayers as revealed by quantitative binding assays and
      phase contrast microscopy. Lewis lung carcinoma cell-induced endothelial cell
      retraction was blocked by specific lipoxygenase inhibitors but not by
      cyclooxygenase inhibitors, suggesting the involvement of a lipoxygenase
      metabolite(s). Radioimmunoassay and high-performance liquid chromatography
      analysis of tumor cell extracts identified 12(S)-HETE as the major lipoxygenase
      metabolite of arachidonic acid and tumor cell generation of 12(S)-HETE was
      specifically blocked by a select 12-lipoxygenase inhibitor N-benzyl-N-hydroxy-5
      phenyl-pentamide. The identity and stereochemistry of tumor cell-derived 12-HETE
      was substantiated by gas chromatography-mass spectrometry analysis and chiral
      phase high-performance liquid chromatography, respectively. Lewis lung carcinoma
      cell adhesion to CD3 monolayers was accompanied by an enhanced 12(S)-HETE
      biosynthesis by tumor cells, which paralleled the tumor cell-induced endothelial
      cell retraction in a cell number-dependent manner. Pretreatment of tumor cells
      with N-benzyl-N-hydroxy-5-phenylpentamide inhibited both increased 12(S)-HETE
      biosynthesis and tumor cell-induced endothelial cell retraction. Highly
      metastatic variants of elutriated B16a cells which had been shown to produce
      large quantities of 12(S)-HETE induced significant CD3 cell retraction, while low
      metastatic subpopulations of B16a cells which synthesized no or little 12(S)-HETE
      did not induce endothelial cell retraction. These results suggest that 12(S)-HETE
      synthesis during tumor cell-endothelial cell interactions may represent a key
      contributory factor in cancer metastasis.

PMID- 8275496
TI  - Transforming growth factor beta production and responsiveness in normal human
      melanocytes and melanoma cells.
AB  - Previous studies have shown that some human melanoma cells express transforming
      growth factor beta (TGF-beta) mRNA and are growth inhibited by exogenous TGF
      beta, suggesting a possible negative autocrine role for this melanoma-derived
      growth factor. To better understand the role of endogenous TGF-beta in the
      development of melanoma, we investigated patterns of TGF-beta protein production
      and responsiveness of human melanoma cells as compared to normal melanocytes.
      Both cultured melanoma cells and normal melanocytes secreted biologically
      inactive, latent TGF-beta protein which, upon acid treatment, became biologically
      active. In melanoma cells, TGF-beta production occurred constitutively, i.e., in
      the absence of exogenous polypeptide growth factors. By contrast, in melanocytes,
      TGF-beta production depended on stimulation by exogenous growth factors such as
      insulin-like growth factor I. Exogenous, bioactive TGF-beta 1 at picomolar
      concentrations inhibited tritiated thymidine uptake of normal melanocytes,
      whereas melanoma cells demonstrated various degrees of resistance to TGF-beta
      induced inhibition of DNA synthesis. Five of six cell lines were less sensitive
      than any of the melanocyte lines tested, and one cell line was completely
      resistant to inhibitory effects of TGF-beta on DNA synthesis. In vivo selection
      of melanoma cells for metastatic ability in athymic mice produced a variant cell
      line that was resistant to TGF-beta 1-induced inhibition of DNA synthesis and
      proliferation. Development of TGF-beta resistance in the variant cell line was
      not associated with changes in TGF-beta cell surface binding. Stable transfection
      of melanocytes with a plasmid expressing the Simian Virus 40 large T-antigen
      rendered these cells resistant to growth inhibition by TGF-beta, suggesting that
      TGF-beta inhibits melanoma/melanocyte growth via interaction with Simian Virus 40
      large T-antigen-responsive transcription elements.

PMID- 8275497
TI  - The involvement of "tumor suppressor" p53 in normal and chronic myelogenous
      leukemia hemopoiesis.
AB  - We investigated the expression of p53 in paraformaldehyde-lysine-periodate fixed
      normal and chronic myelogenous leukemia (CML) hemopoietic cells with flow
      cytometry and two monoclonal antibodies, PAb1801 and the mutant-conformation
      associated PAb240. With both antibodies p53 proteins were detected in more than
      50% of CD34+ cells and in more than 95% neutrophils but were undetectable in the
      CD34- myeloid precursors. The expression of a p53 protein reactive with PAb240
      was closely associated with CD34+/HLA-DR+ cells and with cells in active cell
      cycle, while the p53 protein recognized by PAb1801 was mainly found in CD34+/HLA
      DR- cells and in cells in the G0/G1 phases of the cell cycle. Treatment of
      chronic-phase CML cells with p53 antisense oligonucleotides resulted in
      significantly increased numbers of granulocyte-macrophage colony-forming unit
      colonies in 12 of 17 cases studied. Slightly reduced granulocyte-macrophage
      colony-forming unit colony numbers were observed in one case and no change in the
      four others. In eight samples of normal bone marrow cells, treatment with
      antisense oligonucleotides showed no consistent changes in granulocyte-macrophage
      colony-forming unit numbers. Our data suggest that the expression of the tumor
      suppressor p53 is involved in the regulation of both normal and CML hemopoiesis
      and that the inhibition of p53 expression could modulate the proliferation of CML
      hemopoietic cells and possibly of normal cells.

PMID- 8275498
TI  - Vascularization of carcinomas of the esophagus and its correlation with tumor
      proliferation.
AB  - Vascularization and tumor cell proliferation were analyzed in 33 resected human
      squamous cell carcinomas of the esophagus using the endothelium-specific antibody
      BW 200 and the proliferation-associated antibody Ki-67. Vascular parameters
      (relative capillary volume, relative total vessel volume, vascular surface area,
      and vascular length) as well as the percentage of proliferating tumor cells (Ki
      67 index) were evaluated on frozen sections by a morphometric method. Vascular
      parameters of the normal mucosa exceeded those of tumors significantly, by a
      factor of 1.4-2.3. The mean distance between tumor capillaries and the onset of
      necrosis was 92 +/- 34 microns. Global vascular density did not correlate with
      TNM stage, tumor diameter, or overall tumor proliferation (mean Ki-67 index,
      35.1%; range, 14.2-64.1%). However, a significant negative correlation existed
      between the percentage of proliferating tumor cells per tumor cord and the
      intercapillary distance between capillaries located at the edges of these cords.
      This observation points to the fact that the esophageal cancers were composed of
      multiple tumor cords and that each of these cords possessed its own supply
      capillaries at the base of the cord. The sum of these "supply units" thus
      constitutes an esophageal cancer. The intercapillary distance may reflect the
      oxygenation status of tumor cells, which cannot be predicted on the basis of
      tumor staging or grading.

PMID- 8275500
TI  - Crosstalk at La Bretesche.

PMID- 8275499
TI  - Inhibition by interleukin 4 of leukemia inhibitory factor-, interleukin 6-, and
      dexamethasone-induced differentiation of mouse myeloid leukemia cells: role of c
      myc and junB proto-oncogenes.
AB  - Interleukin 4 (IL-4) inhibited the differentiation of mouse myeloid leukemia M1
      cells induced by leukemia inhibitory factor (LIF), interleukin 6, or
      dexamethasone and conversely enhanced the induction of M1 cell differentiation by
      1 alpha,25-dihydroxyvitamin D3. IL-4 blocked LIF-induced differentiation of M1
      cells when it was added to the culture medium within 10 h after LIF, but IL-4 did
      not block differentiation when it was added 12 h after LIF. These results
      indicate that IL-4 inhibited a critical intermediate step in myeloid leukemia
      cell differentiation. LIF markedly stimulated the expression of junB mRNA within
      2 h but suppressed the expression of c-myb and c-myc after 2- and 12-h treatment,
      respectively. IL-4 did not significantly affect LIF-induced junB expression or
      suppression of c-myb expression. However, it interfered significantly with the
      LIF-induced suppression of c-myc gene expression. Similar results were obtained
      when interleukin 6 was used to induce differentiation of M1 cells. Dexamethasone
      and 1 alpha,25-dihydroxyvitamin D3 did not induce junB gene expression but
      suppressed the expression of c-myb and c-myc. IL-4 also interfered with
      dexamethasone-induced suppression of c-myc gene expression. On the other hand, IL
      4 enhanced 1 alpha,25-dihydroxyvitamin D3-induced down-regulation of c-myc gene
      expression, consistent with its enhancement of differentiation. These results
      indicate that the change in c-myc expression induced by IL-4 in M1 cells is
      closely associated with the effect of IL-4 on the induction of differentiation of
      M1 cells.

PMID- 8275501
TI  - (13C)-substituted sucrose: 13C-1H and 13C-13C spin coupling constants to assess
      furanose ring and glycosidic bond conformations in aqueous solution.
AB  - Sucrose (beta-D-fructofuranosyl alpha-D-glucopyranoside, 1), methyl alpha-D
      fructofuranoside (2), and methyl beta-D-fructofuranoside (3) have been prepared
      by chemical and/or enzymic methods with single sites of 13C-substitution at C-1,
      C-2, C-3, and C-6 of the fructofuranosyl ring. 1H (500 MHz) and 13C (75 and 125
      MHz) NMR spectra of 1-3 have been obtained, yielding 1H-1H, 13C-1H, and 13C-13C
      spin coupling constants that were used to assess furanose ring and glycoside bond
      conformations in aqueous (2H2O) solution. Results show that the conformational
      mobility of the furanosyl ring in 3 is altered when incorporated into 1.
      Furthermore, 13C-13C and 13C-1H spin couplings across the glycosidic linkage
      suggest a psi torsion angle different from that observed in the crystal (phi
      appears similar). Interplay between the strength of the exoanomeric effect and
      hydrogen bonding in solution may be responsible, in part, for the apparent
      conformational flexibility of 1. In addition, spin couplings in 2 and 3 have been
      compared to those measured previously in alpha-D-threo-pentulofuranose (4) and
      beta-D-threo-pentulofuranose (5), respectively, as a means to study the effect of
      glycosidation and hydroxymethyl substitution on the solution conformation of the
      2-ketofuranose ring. The conversion of 4 to 2 is accompanied by minimal
      conformational change, whereas a significant change accompanies the conversion of
      5 to 3, showing that the effect of substitution on ring conformation depends
      highly on ring configuration before and after substitution.

PMID- 8275502
TI  - Solid-state conformations of 2,6-cis- and 2,6-trans-substituted dihydropyran-3
      ones.
AB  - 2,6-Dihydropyran-3-ones carrying substituents at C-2 and C-6 in cis-arrangement
      invariably adopt half-chair conformations in which the ring oxygen and the carbon
      atom next to the carbonyl group are above and below, respectively, the plane
      formed by the other four carbon atoms, i.e., the 2Ho or oH2 conformation. In the
      case of a trans-arrangement of 2,6-substituents, the geometry of the pyranoid
      ring falls into the Bo,6<-->Eo<-->2Ho or thet inverse o,6B<-->oE<-->oH2 section
      of the conformational cycle, depending on the absolute configuration of the
      compound; for two of the dihydropyranones, 4B and 6, a unique skew-boat (SBo,6)
      conformation, fixed between the Bo,6 and Eo geometries, was ascertained, which
      previously has only been observed for pyranoid enelactones.

PMID- 8275503
TI  - Crystal structures of cyclomaltoheptaose (beta-cyclodextrin) complexed with
      ethylene glycol.8.0H2O and glycerol.7.2H2O.
AB  - Single-crystal X-ray diffraction studies were carried out for the title compounds
      at room temperature. The crystal packings are of the cage-type and isomorphous to
      that of beta-cyclodextrin (beta CD) hydrate. In both crystal structures, disorder
      and extensive thermal vibrations of the complexed guest molecules are observed.
      In beta CD-ethylene glycol.8H2O, one ethylene glycol molecule (disordered over
      two discrete sites) and three water molecules (four discrete sites) are included
      in the beta CD cavity. Within the beta CD cavity, all oxygen sites (ordered and
      disordered) are in positions occupied by water molecules in beta CD.12H2O; this
      is only possible because the ethylene glycol molecule adopts the low-energy
      conformation with the O-C-C-O torsion angle approximately 60 degrees and an O...O
      separation of 2.9 A, in which its hydroxyl groups can directly substitute for two
      hydrogen-bonding water molecules. In beta CD-glycerol.7.2H2O, one glycerol
      molecule (disordered over two discrete sites) and two water molecules (two fully
      occupied sites) are included in the beta CD cavity. The general situation in both
      compounds parallels that found earlier in beta CD-ethanol.8H2O. It is assumed
      that the disorder is dynamic, i.e., associated with jumps between the partially
      occupied molecular sites.

PMID- 8275504
TI  - Mode of action of (1-->4)-beta-D-arabinoxylan arabinofuranohydrolase (AXH) and
      alpha-L-arabinofuranosidases on alkali-extractable wheat-flour arabinoxylan.
AB  - Arabinoxylan-derived oligosaccharides were treated with (1-->4)-beta-D
      arabinoxylan arabinofuranohydrolase (AXH) and two types of alpha-L
      arabinofuranosidase, A and B. Analysis of reaction products by high performance
      anion-exchange chromatography indicated the removal of arabinofuranosyl groups
      from singly substituted xylopyranosyl residues. In addition, differences in the
      specificity of these enzymes towards the various differently substituted
      oligosaccharides were observed. 1H NMR spectroscopy and methylation analysis of
      alkali-extractable wheat-flour arabinoxylan treated with AXH confirmed the
      specificity of AXH towards (1-->3)-linked arabinofuranosyl groups on singly
      substituted xylopyranosyl residues. With these techniques, alpha-L
      arabinofuranosidase B was found to cause minor changes in (1-->2)- and (1-->3)
      linked arabinofuranosyl groups on doubly substituted xylopyranosyl residues.

PMID- 8275505
TI  - Mode of action of the xylan-degrading enzymes from Aspergillus awamori on alkali
      extractable cereal arabinoxylans.
AB  - Alkali-extractable cereal arabinoxylan and oligosaccharides of known structure
      derived from it by enzymic hydrolysis were treated with endo-(1-->4)-beta-D
      xylanases I and III from Aspergillus awamori CMI 142717 and the digests subjected
      to analysis by high performance anion-exchange chromatography. Clear differences
      in the mode of action of the two endo-(1-->4)-beta-D-xylanases were observed.
      When counting from the reducing end, at least one unsubstituted xylopyranosyl
      residue adjacent to singly substituted xylopyranosyl residues or two
      unsubstituted xylopyranosyl residues adjacent to doubly substituted xylopyranosyl
      residues cannot be removed by endo-(1-->4)-beta-D-xylanase I. At least two
      unsubstituted xylopyranosyl residues adjacent to singly or doubly substituted
      xylopyranosyl residues cannot be removed by endo-(1-->4)-beta-D-xylanase III.
      beta-D-Xylosidase from the same xylanolytic system was able to remove terminal
      xylopyranosyl residues from the nonreducing end of branched oligosaccharides only
      when two contiguous unsubstituted xylopyranosyl residues were present adjacent to
      singly or doubly substituted xylopyranosyl residues.

PMID- 8275506
TI  - Characterisation by 1H NMR spectroscopy of oligosaccharides derived from alkali
      extractable wheat-flour arabinoxylan by digestion with endo-(1-->4)-beta-D
      xylanase III from Aspergillus awamori.
AB  - Alkali-extractable wheat-flour arabinoxylan, treated with endo-(1-->4)-beta-D
      xylanase III from Aspergillus awamori CMI 142717, was fractionated by Bio-Gel P-2
      size exclusion chromatography at 60 degrees C. Column fractions, corresponding to
      oligosaccharides with degrees of polymerisation from 5 to 10, were collected, and
      subfractionated by high performance anion-exchange chromatography on CarboPac PA
      1. The structures of the oligosaccharides thus obtained were elucidated by 1H NMR
      spectroscopy, showing chains of (1-->4)-linked beta-D-xylopyranosyl residues
      differently substituted at O-3 and/or O-2,3 with alpha-L-arabinofuranosyl groups.
      The structures were different from those obtained with endo-(1-->4)-beta-D
      xylanase I of the same xylanolytic enzyme system.

PMID- 8275507
TI  - Major structural features of the cell wall arabinogalactans of Mycobacterium,
      Rhodococcus, and Nocardia spp.
AB  - The cell wall arabinogalactans of strains of Mycobacterium, Rhodococcus, and
      Nocardia were per-O-methylated, partially hydrolyzed with acid, and the resulting
      oligosaccharides were reduced and per-O-ethylated to yield per-O-alkylated
      oligoglycosyl alditol fragments. Analyses of these fragments by gas
      chromatography-mass spectrometry and of the intact solubilized polysaccharides by
      1H and 13C NMR revealed the major structural features of the different
      arabinogalactans from representatives of the different genera. All of the
      mycobacterial products contained a homogalactan segment of alternating 5-linked
      alpha-galactofuranosyl (Galf) and 6-linked beta-Galf residues. The arabinan
      segment consisted of three major domains, linear 5-linked alpha-arabinofuranosyl
      (Araf) residues and branched (3-->5)-linked Araf units substituted with either 5
      linked Araf or the disaccharide beta-Araf-(1-->2)-alpha-Araf at both branched
      positions. The recognition of these features in in vivo grown Mycobacterium
      leprae is an important development. The arabinan from strains of Nocardia
      contains a nonreducing-end motif composed of the linear trisaccharide, beta-Araf
      (1-->2)-alpha-Araf-(1-->5)-Araf, attached to linear 5-linked alpha-Araf units.
      The galactan segment of the arabinogalactan of Nocardia sp. is composed of linear
      5-linked beta-Galf units substituted in part at O-6 with terminal beta-glucosyl
      units. The two representative strains of Rhodococcus also differed in the
      composition of the galactan moiety; in addition to the 5-linked Galf, 2- and 3
      linked beta-Galf units are present. The reducing end of the galactans, and
      therefore, apparently, of the entire arabinogalactans from all species from all
      genera, are apparently composed of the unit, rhamnosyl-(1-->3)-N-acetyl
      glucosamine, which, in turn, is apparently attached to peptidoglycan via
      phosphodiester linkage.

PMID- 8275508
TI  - Glucuronoxylomannan of Cryptococcus neoformans obtained from patients with AIDS.

PMID- 8275509
TI  - Multistage carcinogenesis--genetic and epigenetic mechanisms in relation to
      cancer prevention.
AB  - The prevention of cancer is, at our present state of knowledge, the most
      effective and inexpensive mode of controlling this disease. Passive cancer
      prevention is practiced voluntarily or, in part, through governmental regulation
      in many parts of the world. However, active cancer prevention by the
      administration of vaccines, dietary factors, antihormones, or other agents is
      likely to be the most effective mechanism of cancer prevention in humans.
      Carcinogenesis develops in three defined stages--initiation, promotion, and
      progression--the first and third resulting from irreversible genetic changes in
      the cell, whereas the intermediate stage of promotion involves an epigenetic
      alteration of the expression of the genome and cell division. Thus, the stage of
      promotion is the most effective site to target for both active and passive cancer
      prevention. A review of the modalities presently used in cancer prevention, both
      active and passive, demonstrates that all such methods involve an inhibition
      and/or reversal of this intermediate stage, thus preventing the development of
      the malignant process. Future advances in cancer prevention will depend on better
      knowledge of the mechanisms of the stages of carcinogenesis in order that
      rational preventive agents and formats may be used in altering or modifying the
      appropriate stage(s) of neoplastic development.

PMID- 8275510
TI  - Detection of c-Ha-ras oncogene expression in pleural and peritoneal smear
      effusions by in situ hybridization.
AB  - This study was undertaken to determine the presence of the c-Ha-ras protooncogene
      in pleural and peritoneal effusions. Cells from 40 pleural and peritoneal fluids
      from patients with malignant and nonmalignant diseases were studied by in situ
      DNA hybridization utilizing a biotinylated probe. The results were correlated
      with those obtained by conventional cytological methods. A cytological diagnosis
      of metastatic carcinoma was established in 67% of the patients with malignancy
      and effusion, and in 6% of the patients with benign disease accompanied by
      effusion. On the other hand, a relatively high proportion of ras expression was
      observed in 38% of the cases representing benign and reactive effusions and as
      high as 88% in the cases with malignant tumor and effusion. These results suggest
      that the ras oncogene may have an important role in differentially diagnosing
      benign and reactive mesothelial cells from malignant cells.

PMID- 8275511
TI  - The misuse of attributable and prevented fractions in the evaluation of screening
      in case-control studies.
AB  - Methodological problems of evaluating screening programs in case-control studies
      have been the subjects of controversial discussion in recent years. The
      increasing number of published papers presenting results of case-control studies
      on the evaluation of cancer screening during the last few years demonstrate that
      this design has rapidly gained popularity in cancer epidemiology, although the
      methodological criticism has not been solved yet and is usually not reflected in
      the interpretation of the study results. A new development in this area has been
      the incorporation into the evaluation of some measure of the population impact of
      screening programs. This paper discusses the application of these measures
      (attributable and prevented fractions) to screening situations. The implicit
      assumptions required for their valid interpretation are delineated. Primarily, it
      is our intention to raise the flag of caution against the naive practical
      application and overoptimistic interpretation of attributable and prevented
      fraction estimates derived from case-control studies on the evaluation of
      screening.

PMID- 8275512
TI  - A case-control study of malignant melanoma of the trunk among white males in
      upstate New York.
AB  - To address the increase in the incidence of cutaneous melanoma in upstate New
      York in recent decades, a case-control study was conducted of the constitutional
      and environmental risk factors for malignant melanoma of the trunk among white
      males. Cases were identified from the New York Cancer Registry from 1977 through
      1979 (the period of the greatest relative increase in incidence), and controls
      were selected using random digit dialing methods. A total of 324 cases or their
      next-of-kin and 415 controls were interviewed regarding physical and
      sociodemographic characteristics, lifestyle habits, and medical histories. The
      following variables were statistically significant in the final logistic
      regression analysis: birthmarks (O.R. = 3.87); sunburn easily (O.R. = 1.83); fair
      skin tone (O.R. = 1.63); northern European ancestry (O.R. = 1.51); blue eye color
      (O.R. = 1.46); and participation in water sports (O.R. = 2.02). Interaction terms
      between constitutional and environmental variables resulted in a significant
      relationship between the presence of freckles and bathing two or more times per
      day. Among freckled individuals, those who bathed more than once per day had a
      sixfold elevation in the risk compared to those who bathed less often. In
      comparison, the odds ratio for frequent bathing among men without freckles was
      only 1.24. The data suggest the following hypothesis for further study: the
      possibility that frequent bathing may be deleterious, especially among freckled
      individuals or those with pigmented nevi.

PMID- 8275513
TI  - Surveillance for colorectal neoplasia: is patient adherence following treatment a
      problem?
AB  - This study was conducted in order to assess prospective adherence to surveillance
      colonoscopy and fecal occult blood testing (FOBT) at 1 year following treatment
      for an index lesion among colorectal cancer and polyp patients. The investigation
      was carried out in cooperation with two gastroenterology and two surgical
      practices in Philadelphia and surrounding communities. Subjects in this study
      were patients who were treated for colorectal cancer (N = 9) or polyps (N = 169)
      and were recommended to undergo surveillance colonoscopy at 12 months following
      treatment. Overall, 96 (54%) subjects underwent surveillance colonoscopy. Of the
      178 subjects included in the study, 52 (29%) were willing to participate in an
      assessment of FOBT sensitivity in surveillance. Of the 52 subjects who were
      mailed an FOBT packet, 24 (46%) actually returned specimen. Of the 24 patients
      who returned FOBTs, 17 (71%) also underwent colonoscopy, whereas only 10 (36%) of
      26 patients who did not do FOBTs underwent colonoscopy. These findings indicate
      that adherence to surveillance is low, and that adherence to FOBT may be a marker
      for adherence to colonoscopy.

PMID- 8275514
TI  - Attenuated veterinary virus vaccine for the treatment of cancer.
AB  - Attenuated (nonpathogenic) avian viruses have been used as a form of nonspecific
      immunological treatment for advanced human cancer. For this study, we used
      Newcastle disease virus (NDV) vaccine MTH-68/N in an open phase II/B, placebo
      controlled (26 patients), multicenter clinical trial for the treatment of 33
      patients with advanced cancers. NDV (4000 U/day) or placebo was administered by
      inhalation twice weekly. During the 6-month trial, the size and presence of
      primary tumors and metastases were objectively monitored at five institutions by
      radiologists unaware of the type of treatment that was given. Regression of
      tumor(s) and/or metastases were observed in eight cases treated with virus (vs.
      none in the placebo group; p < 0.01). Ten additional patients treated with NDV
      had no further progression of their tumor sizes, whereas tumor stabilization was
      noted in only two control patients. Objective, favorable responses (regressions
      plus stabilization) to virus therapy thus occurred in a total of 18 patients
      (55%) compared to 2 patients in the placebo group (8%; p < 0.01). Two cases of
      complete remission were noted in the group treated with NDV. Patients receiving
      virus therapy had a higher rate of survival at 1 to 2 years. Of 33 patients
      receiving virus vaccine, 22 survived 1 year, compared to only 4 of 26 patients in
      the control group (p < 0.02). After 2 years, all seven survivors in the study
      were in the virus therapy group. There were no 2-year survivors in the control
      group (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275515
TI  - Spotlight on excitation-contraction coupling in the mammalian myocardium.
      International symposium, Leeds, 26-29 July 1992. Proceedings.

PMID- 8275516
TI  - Reconstructing the heart: a challenge for integrative physiology.

PMID- 8275517
TI  - Sodium/calcium exchanger in heart muscle: molecular biology, cellular function,
      and its special role in excitation-contraction coupling.
AB  - The Na/Ca exchanger has been examined with respect to its molecular biology, its
      cellular function, and its role in excitation-contraction coupling. The Na/Ca
      exchanger plays a central part in excitation-contraction coupling, setting the
      level of sarcoplasmic reticular calcium and contributing to the triggering of
      sarcoplasmic reticular calcium release. Functional biophysical studies with
      isolated single cells and caged calcium provide evidence that the Na/Ca exchanger
      works as a two step sequential transporter. In the heart there are about 250
      exchangers.mu-2, operating at a turnover rate of up to about 2500.s-1, with the
      exchanger carrying -2.56 charges under normal conditions. The Na/Ca exchanger has
      been recently cloned from diverse mammalian species and several tissues and is
      largely conserved. It is clear, however, that the function of the Na/Ca exchanger
      is different in the different tissues. Thus work is in progress in several
      laboratories, including ours, to determine how the Na/Ca exchanger achieves its
      tissue specific function. Several modulatory motifs have been seen in studies of
      the exchanger that may explain some of the tissue specific differences.
      Interestingly the modulation of the Na/Ca exchanger (for example, by protons,
      sodium, calcium, ATP, calmodulin) seems to arise from interactions with the
      intracellular loop.

PMID- 8275518
TI  - Modulation of cardiac contractility by alpha 1 adrenoceptors.

PMID- 8275519
TI  - One hump or two? The triggering of calcium release from the sarcoplasmic
      reticulum and the voltage dependence of contraction in mammalian cardiac muscle.
AB  - We have examined the hypothesis that the sarcolemmal Na/Ca exchanger is able to
      trigger calcium release from the sarcoplasmic reticulum in a direct fashion. We
      propose that when the cardiac muscle membrane is depolarised, for instance during
      the upstroke of the action potential or a square voltage clamp pulse, the voltage
      dependent Na/Ca exchanger generates an initial "spike" of calcium entry which is
      sufficient to trigger a fraction of the normal sarcoplasmic reticular calcium
      release, via calcium induced calcium release. For the last 20 years, it has been
      widely considered that calcium entry through L-type calcium channels is the only
      trigger for calcium release from sarcoplasmic reticulum in cardiac muscle. In the
      first section of this review, we examined some of the earlier studies of
      excitation-contraction coupling which used multicellular preparations of cardiac
      muscle. We suggested that these earlier studies do not support the idea that
      calcium entry via the calcium current (ICa) is the only trigger for sarcoplasmic
      reticular release. In contrast, more recent studies using isolated myocytes have
      supported ICa as the only trigger. However, these were performed mostly with a
      low or absent sodium inside the cell, or with an increased intracellular calcium
      buffering, or with other altered internal ions (eg, high magnesium or caesium in
      the pipette) or at a relatively low temperature. All these factors may have
      reduced or abolished the initial spike of calcium entry which the Na/Ca exchanger
      is expected to generate at the start of depolarisation. New studies on myocytes
      are presented, using conditions where cells are dialysed minimally, or where a
      normal level of internal sodium is preserved deliberately.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8275520
TI  - Mechanisms of excitation-contraction coupling studied using the principle of
      transient perturbation.
AB  - We have studied the responses to a brief interruption of a train of steady state
      beats, namely: (1) a single prolonged depolarisation within the train; (2) a
      single short interval within the train; (3) a single long interval within the
      train. These responses are predicted by a two compartment model of intracellular
      calcium handling. They are characterised by the following phenomena. (1)
      Prolongation of one depolarisation/action potential in the steady state train
      causes potentiation of the following beat. We postulate on the basis of the
      published evidence that this may be due to "reversed" sodium/calcium exchange
      during late systole leading to extra calcium entry during the prolonged
      depolarisation. (2) Postextrasystole potentiation is postulated to share this
      mechanism when a depolarisation (extrasystole) is introduced immediately after
      one of the steady state depolarisations (single short interval). The
      postextrasystolic beat is then potentiated. (3) A single short interval during
      the steady state train also leads to attenuation of contractile force on the beat
      immediately after the short interval, that is, the extrasystole. Mechanical
      restitution is the term applied to the recovery of this force with increasing
      interval. This consists of two phases. The initial rapid phase is ryanodine and
      caffeine insensitive, indicating possible independence of sarcoplasmic reticular
      function. We postulate that a "membrane compartment" of internal calcium may be
      responsible. The second, slower, phase of mechanical restitution is ryanodine and
      caffeine sensitive, indicating that it is likely to be a property of the
      sarcoplasmic reticulum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275521
TI  - Control of the calcium pump of cardiac sarcoplasmic reticulum. A specific role
      for the pentameric structure of phospholamban?
AB  - Intracellular sources of calcium provide most of that required for cardiac muscle
      contraction. Regulation of the filling of these calcium stores by control of the
      enzyme responsible for calcium uptake, the sarcoplasmic reticular calcium pump,
      provides a mechanism by which the contractile properties of the heart can be
      adapted. In fact, this single biochemical event accounts for most of the changes
      in calcium handling associated with beta adrenergic stimulation. The calcium pump
      of cardiac sarcoplasmic reticulum is regulated by the phosphorylation status of a
      second sarcoplasmic reticular component, phospholamban. This is a low molecular
      weight membrane protein which assembles as an oligomer (homopentamer) and
      inhibits pump function by physical interaction with a "regulatory" motif on the
      pump. This interaction (and the state of inhibition) is broken following
      phosphorylation of phospholamban by cAMP-, cGMP, or Ca2+/calmodulin dependent
      protein kinases. This model of pump control shares a number of features
      associated with control of the plasma membrane calcium pump; however, the
      oligomeric arrangement of the regulator is specific for the sarcoplasmic
      reticular ATPase. The functional significance of the oligomer is currently
      unknown, but this format may provide functional advantages such as (1) offering
      an effective substrate structure for kinase/phosphatase, promoting rapid changes
      in phosphate status; (2) facilitating intrapentamer cooperation, translating low
      stoichiometric phosphorylation into large changes in pump function; or (3)
      coordinating multiple pump units around a single pentamer thus restricting
      conformational freedom and suppressing enzyme activity.

PMID- 8275522
TI  - Competition and redistribution among calcium transport systems in rabbit cardiac
      myocytes.
AB  - Normally the sarcoplasmic reticular calcium pump and sarcolemmal Na/Ca exchange
      compete and are the primary mechanisms responsible for reducing [Ca]i during
      cardiac relaxation. The sarcolemmal calcium pump and mitochondrial calcium uptake
      are much slower, but may also participate in [Ca]i regulation. The aim of this
      study was to provide a clearer understanding of the interaction of these
      mechanisms. Myocyte shortening and [Ca]i transients (using indo-1 fluorescence)
      were measured in rabbit ventricular myocytes, with similar results. The t1/2 of
      twitch relaxation was 0.17(SEM 0.03) s. Contractures induced by 10 mM caffeine
      (caffeine contraction) relaxed more slowly [t1/2 = 0.54(0.07) s] due to
      prevention of sarcoplasmic reticular calcium uptake. When the Na/Ca exchange was
      also blocked by perfusion with 0Na,0Ca solution, the peak of the caffeine
      contraction was increased (by 44%) and relaxation was slowed about 16-fold [t1/2
      = 8.8(0.8) s]. Blocking mitochondrial calcium uptake by including 1 microM FCCP +
      1 microM oligomycin in the 0Na,0Ca solution slowed the relaxation of the caffeine
      contraction further [t1/2 = 19.7(3.2) s]. Inhibition of the sarcolemmal calcium
      pump by perfusion with 0Na, 10 mM Ca during caffeine contraction also increased
      the relaxation t1/2 to 27.5(6.9) s. Inhibition of all four calcium transport
      systems almost abolished relaxation. It is also shown that calcium which was
      taken up by the mitochondria during relaxation of the caffeine contraction in
      0Na,0Ca gradually redistributed (with tau = 41 s) back to the sarcoplasmic
      reticulum after caffeine was removed. A second caffeine contraction could then be
      elicited.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275523
TI  - Calcium and the oxygen paradox.
AB  - When myocardial cells are reoxygenated after a prolonged period of energy
      depletion, they rapidly hypercontract. In tissue, hypercontracture induced by
      reoxygenation is accompanied by cytolysis ("oxygen paradox"). Recent studies have
      indicated that severe cytosolic Ca2+ overload and reactivation of energy
      production represent the causal key factors for the deleterious hypercontracture,
      through the following mechanism: prolonged energy depletion leads to a
      progressive cytosolic Ca2+ overload in cardiomyocytes; when oxidative
      phosphorylation is then resumed with the resupply of oxygen, activation of the
      myofibrils at (still) increased cytosolic Ca2+ concentrations provokes a
      sustained maximal force development and consecutive mechanical cell injury. This
      injury can largely be prevented when the contractile machinery is inhibited
      during the initial phase of reoxygenation. In the model of isolated cells it has
      been shown that a normal cytosolic Ca2+ control can be reestablished upon
      reoxygenation. This seems to explain why contractile blockade is needed only
      temporarily for the prevention of reoxygenation induced hypercontracture and
      cellular deterioration. Temporary contractile blockade at the onset of
      reperfusion has also been shown to protect the heart in vivo against lethal
      reperfusion injury.

PMID- 8275524
TI  - Arrhythmogenicity of the hypertrophied and senescent heart and relationship to
      membrane proteins involved in the altered calcium handling.
AB  - The high incidence of arrhythmias in human left ventricular hypertrophy has been
      well established but the mechanisms of arrhythmias are not well defined. In
      attempt to clarify these mechanisms, we tried to determine if a relationship
      might exist in the hypertrophied or senescent hearts between the incidence of
      arrhythmias and alterations in the gene expression of the main membrane proteins
      involved in the regulation of calcium movements. Holter monitoring was used in
      young and senescent rats where hypertrophy had been induced by aortic stenosis
      and hyperthyroidism (young rats) or by DOCA-salt treatment (senescent rats).
      Different types of spontaneous arrhythmias were detected. In the aortic stenosis
      group, the heart rate and the number of supraventricular premature beats were
      increased significantly, whereas the number of ventricular premature beats was
      increased in some animals but not in all. In senescent rats, the numbers of
      ventricular and supraventricular premature beats and the incidence of
      atrioventricular block were very high. At the cellular level, the density of
      calcium channels from the sarcolemma and of the alpha 1 subunit of the Na+/K(+)
      ATPase were unchanged in the hypertrophied and senescent hearts but most of the
      proteins involved in the regulation of calcium movements (calcium release channel
      and Ca(2+)-ATPase from the sarcoplasmic reticulum, Na+/Ca2+ exchange, and beta
      adrenergic and muscarinic receptors from the sarcolemma) have a decreased density
      or activity. These changes might account for the slowing of the maximum
      shortening velocity and the impaired contractility of the hypertrophied and
      senescent hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275525
TI  - On the involvement of a cyclosporin A sensitive mitochondrial pore in myocardial
      reperfusion injury.
AB  - Mammalian cardiomyocytes may withstand prolonged periods of ischaemia, only to
      die on reperfusion. We review data that implicate mitochondrial dysfunction as a
      basis for reperfusion induced cell injury, and present some new evidence that
      suggests that such a mechanism operates in intact cardiomyocytes. The
      mitochondrial dysfunction is the consequence of the opening of high conductance
      pores in the inner mitochondrial membrane, which uncouple mitochondrial oxidative
      phosphorylation, promoting ATP hydrolysis. The conditions required to open the
      pores correlate closely to conditions that prevail upon reperfusion of the
      ischaemic heart: a high [Ca2+]i and Pi, low [ATP], and oxidative stress. Pore
      opening is suppressed by physiological concentrations of ATP. Pore opening may be
      prevented by cyclosporin A. Studies in isolated myocytes show that mitochondria
      become uncoupled after reoxygenation, and that this is associated with the
      hypercontracture that signals cell death. Cyclosporin A reduces the proportion of
      hypercontracted myocytes in populations of cells rendered anoxic.

PMID- 8275526
TI  - Heterogeneity of action potential waveforms and potassium currents in rat
      ventricle.
AB  - OBJECTIVE: The ionic mechanisms for differences in action potential waveforms in
      rat left ventricle were studied by recording L-type Ca2+ current, transient
      outward K+ current, and inwardly rectifying background K+ current in single
      myocytes. METHODS: Single cells were obtained from adult rat hearts by enzymatic
      dispersion of tissue segments from the epicardium at the apex and the endocardium
      at the base of the left ventricle. Whole cell voltage clamp methods together with
      cell shortening measurements were used to identify the K+ currents involved in
      early and late repolarisation and to correlate changes in action potential shape
      with inotropic responses. 4-Aminopyridine was used to block the transient outward
      K+ current, I(t), to evaluate the contribution of this current to repolarisation.
      RESULTS: Action potential recordings demonstrated that cells from endocardial
      tissue at the base of the left ventricle have a considerably longer action
      potential than those from epicardial tissue at the apex. 4-Aminopyridine had a
      much more pronounced action potential lengthening and inotropic effects on cells
      from epicardium than on myocytes from endocardium suggesting that I(t) is larger
      in the epicardium. Voltage clamp measurements confirmed this. In contrast, the L
      type Ca2+ current, the resting membrane potential, and the inwardly rectifying
      background K+ current were very similar in these two regions of left ventricle.
      CONCLUSIONS: One significant factor contributing to the heterogeneity of action
      potential waveforms in rat left ventricle is a differential distribution of a Ca+
      independent transient outward K+ current, I(t). Regional differences in action
      potential duration have important implications for the gradient of repolarisation
      in rat left ventricle, for the genesis of the T wave of the electrocardiogram,
      and for both electrical and mechanical restitution (refractoriness).

PMID- 8275527
TI  - Changes in mitochondrial calcium concentration during the cardiac contraction
      cycle.
AB  - OBJECTIVE: The aim was to examine whether mitochondrial Ca2+ fluxes are high
      enough to change mitochondrial and cytosolic calcium concentration during the
      contraction cycle. METHODS: Isolated guinea pig ventricular myocytes were
      stimulated with paired voltage clamp pulses until contractions were maximal (2 mM
      [Ca2+]o, 36 degrees C). At defined times of diastole or systole, the cells were
      shock frozen. Electron-probe microanalysis measured the concentration of total
      calcium in mitochondria (sigma Ca(mito)) and surrounding cytosol (sigma Cac).
      Other experiments were performed to evaluate DNP sensitive mitochondrial Ca2+
      uptake from depolarisation induced [Ca2+]c transients (K5indo-1 fluorescence).
      RESULTS: At end of diastole, sigma Ca(mito) was 446 mumol.litre-1. During
      systole, sigma Ca(mito) increased with a 20 ms delay. A peak sigma Ca(mito) of
      1050 mumol.litre-1 was measured 40 ms after start of systole, while 95 ms after
      start of systole sigma Ca(mito) had fallen to 530 mumol.litre-1. From the changes
      in sigma Ca(mito) the rates of net mitochondrial Ca2+ flux were estimated at 100
      nmol.s-1 x mg-1 protein for Ca2+ influx and 36 nmol.s-1 x mg-1 protein for Ca2+
      egress. Decay of sigma Ca(mito) was coupled to a rise in sigma Na(mito). sigma
      Cl(mito) and sigma K(mito) rose and fell in parallel with sigma Ca(mito),
      suggesting Ca2+ activation of mitochondrial anion and cation channels. Activation
      of the non-specific permeability can be excluded. Block of mitochondrial Ca2+
      uptake with DNP (100 microM) or FCCP (10 microM) increased the amplitude of the
      [Ca2+]c transients for 1-3 min by about 50%; evaluation of mitochondrial Ca2+
      uptake from DNP sensitive difference signals, however, was hampered by
      sequestration of mitochondrial Ca2+ into the sarcoplasmic reticulum. CONCLUSIONS:
      Mitochondrial calcium content changes during each individual contraction cycle; a
      substantial amount of calcium is taken up during the systole and released during
      later systole and diastole.

PMID- 8275528
TI  - Changes in the principal free intracellular amino acids in the Langendorff
      perfused guinea pig heart during arrest with calcium-free or high potassium
      media.
AB  - OBJECTIVE: Many amino acids have been shown to be cotransported with Na+ in a
      variety of tissues but evidence for an Na+ dependent efflux in the heart is
      restricted to taurine. The aim of this study was to determine the intracellular
      levels of the principal amino acids, alanine, glutamine, glutamate, and
      aspartate, when the heart was beating at normal or low temperature, during
      exposure to strophanthidin, and when the heart was arrested with either
      Ca2+,Mg(2+)-free Tyrode solution (a condition known to raise intracellular Na+)
      or with a high K+ Tyrode solution. METHODS: Guinea pig hearts, mounted on a
      Langendorff apparatus, were perfused with a variety of media and the level of
      amino acids in the ventricles determined using high performance liquid
      chromatography. RESULTS: During perfusion with normal Tyrode solution a time
      dependent fall in tissue glutamine, glutamate, and aspartate, but not alanine,
      was observed. Exposure of the beating heart to strophanthidin (0.2 mM) or cooling
      to 20 degrees C, which should induce a similar increase in [Na+]i but have
      opposite effects on metabolism, had different effects on tissue amino acids.
      Cooling did not affect the level of amino acids whereas strophanthidin produced
      an effect consistent with an activation of a glutamate-alanine aminotransferase.
      Arresting the heart with Ca2+,Mg(2+)-free Tyrode solution provoked a marked fall
      in all amino acids which was associated with their appearance in the effluent.
      This loss of the amino acids was antagonised by conditions known to reduce the
      rise in intracellular Na+ concentration and increased by inhibition of the Na+
      pump. Comparison of the beating heart with the heart arrested with high K+ Tyrode
      solution showed no difference in the levels of glutamate or aspartate, with a
      small fall in alanine and taurine and raised glutamine. CONCLUSIONS: The data
      from beating or arrested hearts are consistent with the presence of amino
      acid/Na+ cotransport systems but the levels of amino acids free in the sarcoplasm
      depend on an interaction between amino acid transport driven by the changes in
      the Na+ gradient and the effects of metabolism.

PMID- 8275529
TI  - Cation conduction in the calcium release channel of the cardiac sarcoplasmic
      reticulum under physiological and pathophysiological conditions.
AB  - OBJECTIVE: The aim was to perform a theoretical and experimental study of the
      possible variations in Ca2+ current through the open cardiac sarcoplasmic
      reticular Ca2+ release channel under the ionic conditions associated with
      physiological and pathophysiological states. METHODS: The sheep cardiac
      sarcoplasmic reticular Ca2+ release channel was purified and reconstituted into
      planar phospholipid bilayers for study under voltage clamp conditions. Single
      channel current-voltage relationships were measured under putative physiological
      conditions with 1, 5, and 10 mM intraluminal Ca2+. The mathematics of a computer
      model based on Eyring rate theory were extended to include the interactions of
      three permeant ions. RESULTS: A model used previously to describe ionic
      conduction under simpler ionic conditions was able to predict the interaction of
      Ca2+, Mg2+, and K+ in the probable physiological range over the voltage range of
      interest. The predicted Ca2+ current under ionic conditions proposed to occur at
      the end of diastole is sensitive to relatively small changes in holding potential
      which suggests the need for adequate charge compensation across the sarcoplasmic
      reticular membrane. Theoretically, it was predicted that variations in
      intraluminal Ca2+, such as may occur in Ca2+ overload and other conditions, and
      variations in cytosolic Mg2+, which may occur in myocardial stunning, may
      significantly affect Ca2+ flux through the open Ca2+ release channel.
      CONCLUSIONS: Variations in permeant ion concentration such as may occur in
      physiological and pathophysiological states may significantly affect the quantity
      of Ca2+ released from the cardiac sarcoplasmic reticulum.

PMID- 8275530
TI  - The relative contributions of different intracellular and sarcolemmal systems to
      relaxation in rat ventricular myocytes.
AB  - OBJECTIVE: The aim was to estimate the relative contributions of the various
      intracellular and sarcolemmal systems to the relaxation of the systolic calcium
      transient. METHODS: The experiments were performed on isolated rat ventricular
      myocytes. The cells were loaded with the fluorescent indicator indo-1 in order to
      measure [Ca2+]i. RESULTS: The application of caffeine to release calcium from the
      sarcoplasmic reticulum produced a rise of [Ca2+]i which decayed about 7-8 times
      more slowly than the electrically stimulated calcium transient. This suggests
      that the sarcoplasmic reticulum accounts for about 87% of the calcium removal.
      The rate of decay of the caffeine response was decreased to about 33% of the
      control by inhibiting the Na-Ca exchange with Ni2+. In the presence of Ni2+ the
      rate could be inhibited further by inhibiting either the sarcolemmal Ca-ATPase
      (by increasing extracellular calcium concentration, [Ca2+]o) or the mitochondria
      (with FCCP and oligomycin). The relative contributions of the various processes
      were estimated to be: sarcoplasmic reticulum 87%, mitochondria 1.7%, Na-Ca 8.7%,
      sarcolemmal Ca-ATPase 2.6%. CONCLUSIONS: These experiments show that the Na-Ca
      exchange accounts for 67% of the calcium removal not mediated by the sarcoplasmic
      reticulum. This is a smaller fraction than in rabbit cardiac cells and highlights
      the importance of the Ca-ATPase in the rat heart.

PMID- 8275531
TI  - Triggered propagated contractions in human atrial trabeculae.
AB  - OBJECTIVE: Mechanical stretch and rapid release of locally damaged regions of rat
      cardiac trabeculae due to contraction of undamaged cells during the regular
      twitch have been shown to trigger local aftercontractions in the damaged region.
      These aftercontractions appear to propagate along the length of the trabeculae
      and to precede triggered arrhythmias. The aim of this study was to determine
      whether triggered propagated contractions can also be elicited in human cardiac
      tissue. METHODS: Trabeculae were dissected from a biopsy of the right atrial
      appendage which was obtained during cardiac surgery. They were mounted
      horizontally, superfused with a modified Krebs-Henseleit solution, and monitored
      with a video system. Force was measured with a silicon strain gauge; sarcomere
      length was measured with laser diffraction techniques. Triggered contractions
      were elicited in 10 trabeculae following trains of 15 stimuli at a rate of 2 Hz,
      separated by 15 s rest intervals, at 21 degrees C and a [Ca2+]o above 5.0 mM.
      RESULTS: Both video analysis and sarcomere length recordings showed that the
      contractions started at one end of the trabeculae and travelled from there as a
      localised contraction along the muscle. Increasing [Ca2+]o or the number of
      conditioning stimuli increased force of the stimulated twitches up to a maximum;
      further increase of [Ca2+]o or the number of stimuli was accompanied by a
      decrease of force. Force of the triggered propagated contractions increased
      monotonically with increasing [Ca2+]o and number of stimuli, while the interval
      between last stimulus and the peak of the force transient (or latency) decreased
      progressively, and propagation velocity increased monotonically. Propagation
      velocity was calculated from the interval between peak sarcomere shortening at
      two sites and the distance between these sites, as well as from the ratio between
      the length of the muscle and the duration of the force transient in the remainder
      of the trabeculae. With increasing temperature at constant [Ca2+]o twitch force
      increased while latency, force, and duration of the force transient decreased. At
      37 degrees C, localised contractions travelling along the muscle could still be
      induced at sufficiently increased [Ca2+]o. For all interventions, propagation
      velocity varied from 0.8 to 3.9 mm.s-1. CONCLUSIONS: Contractions can be elicited
      in human atrial cardiac trabeculae. These contractions have the same basic
      characteristics as the triggered propagated contractions that have been described
      previously in rat ventricular trabeculae.

PMID- 8275532
TI  - Continuous measurements of cytoplasmic ATP in single cardiomyocytes during
      simulation of the "oxygen paradox".
AB  - OBJECTIVE: It is now possible to monitor cytoplasmic ATP in single cardiomyocytes
      and it has recently been shown that cardiomyocytes exposed for several minutes to
      metabolic inhibitors undergo an abrupt rigor mediated shortening which coincides
      with a sudden fall in cytoplasmic ATP, from approximately 150 mumol.litre-1 to a
      few micromolar or less. The objective of this work was to monitor cytoplasmic ATP
      during simulated reoxygenation of a poisoned cardiomyocyte. METHODS: Firefly
      luciferase was injected into a single cell and the light signal generated when
      luciferin was superfused was monitored. Calibration of the signal is complicated
      by a transient enhancement of the signal (possibly the result of complex
      luciferase kinetics), and by uncertainties about cytoplasmic pH. RESULTS: The
      data indicate that millimolar levels of cytoplasmic ATP are restored within 1-2
      min of cyanide removal. CONCLUSIONS: Cytoplasmic free calcium is known to rise
      after poisoned cells undergo shortening, so it is conceivable that the
      restoration of cytoplasmic ATP in a cell in which free calcium is at micromolar
      levels may provide a plausible cellular mechanism for the "oxygen paradox".
      Reoxygenation induces large amplitude, but slow, oscillations in free calcium
      which, together with the millimolar levels of ATP indicated here, could provide
      the stimuli for generating the uncoordinated mechanical forces that are prevalent
      in the oxygen paradox.

PMID- 8275533
TI  - Intramitochondrial free calcium in cardiac myocytes in relation to dehydrogenase
      activation.
AB  - OBJECTIVE: The aim was to quantitate intramitochondrial free Ca2+ ([Ca2+]m) in
      cardiac myocytes under conditions of stimulation previously shown to cause
      activation of pyruvate dehydrogenase. METHODS: [Ca2+]m was monitored in single,
      isolated rat cardiac myocytes using fluorescence microscopy following the loading
      of the cells with the fluorescent chelating agent indo-1, in its permeant
      acetoxymethylester form, and the selective quenching of cytosolic fluorescence
      with MnCl2. The extent of contraction upon electrical stimulation was also
      measured. RESULTS: Electrical stimulation at 2 Hz and higher frequency raised
      [Ca2+]m significantly, and this was potentiated by exposure to isoprenaline.
      However, isoprenaline had no effect in quiescent cells, in which [Ca2+]m was
      raised above resting values by partial replacement of Na+ in the medium. The
      mitochondrial uncoupling agent carbonylcyanide p-trifluoromethoxyphenylhydrazone
      (FCCP) raised [Ca2+]m in unstimulated cells, but lowered it in cells subjected to
      electrical stimulation at 2 Hz or more, to partial Na+ replacement, or to the
      alkaloid veratridine. CONCLUSIONS: The values of [Ca2+]m in quiescent myocytes
      (approximately 100 nmol.litre-1) would be associated with very little activation
      by Ca2+ of pyruvate dehydrogenase phosphatase, based on determination of K0.5
      value of 650 nmol.litre-1 in work with mitochondrial suspensions. By contrast,
      the values of [Ca2+]m associated with electrical stimulation at 2 Hz or greater
      in the presence of beta adrenergic activation (> 500 nmol.litre-1) would be
      associated with significant dehydrogenase activation. The effect of beta
      adrenergic activation is only seen in the presence of electrical stimulation and
      probably involves enhancement of systolic transients in cytosol [Ca2+]. Effects
      of uncoupling agents validate the conclusions on the direction and magnitude of
      the mitochondrial Ca2+ gradient in situ in living myocytes.

PMID- 8275534
TI  - Excitation-contraction coupling in rat heart: influence of cyclosporin A.
AB  - OBJECTIVE: The aim was to investigate the steps in the excitation-contraction
      coupling process by which chronic exposure to cyclosporin A (cyclosporin) affects
      twitch force development by rat cardiac trabeculae. METHODS: The interval
      dependence and [Ca2+]o dependence of twitch force development by intact
      trabeculae isolated from myocardium of untreated rats and rats treated with
      cyclosporin (15 mg.kg-1.d-1 for 21 d) were studied in Krebs-Henseleit solution (K
      H; pH 7.4 and 25 degrees C) and the force-pCa relation was examined in all
      trabeculae. RESULTS: The force-[Ca2+]o relation of cyclosporin treated trabeculae
      was shifted leftward compared to that of controls, but these trabeculae generated
      35% less stress (force/cross sectional area) at optimal [Ca2+]o. Unlike control
      trabeculae, cyclosporin treated trabeculae showed spontaneous activity at all
      diastolic intervals, even at low [Ca2+]o. Treated and control trabeculae
      generated the same maximum stress [control: 78.1 (SEM 7.7) mN.mm-2, cyclosporin
      treated: 70.2(7.4) mN.mm-2] in the presence of extracellular Sr2+ ions in the
      Krebs-Henseleit medium. Maximum stress observed in the presence of Sr2+ was
      similar to the stress generated by maximum activation of chemically skinned
      trabeculae in both groups [control: 70(4.6) mN.mm-2; cyclosporin treated: 73(6.2)
      mN.mm-2). The force-pCa relation of cyclosporin treated muscles and control
      muscles after skinning were also indistinguishable [control pCa50 = 5.56(0.04);
      cyclosporin treated pCa50 = 5.58(0.03)]. The twitch force-interval relation at
      0.7 mM [Ca2+]o in intact control trabeculae revealed postrest potentiation with a
      maximum [equivalent to 70% of twitch force at optimal [Ca2+]o -61.0(2.1) mN.mm-2]
      at 100 s and subsequent rest depression. Under the same conditions, twitch force
      development by cyclosporin treated trabeculae was closer to optimal force
      [41.4(7.1) mN.mm-2] at all intervals, and rest potentiation was reduced.
      Pronounced rest potentiation (as well as postextrasystolic potentiation) was
      still observed in cyclosporin treated trabeculae at [Ca2+]o < 0.7 mM.
      Postextrasystolic potentiation was reduced at 0.7 mM [Ca2+]o in these trabeculae,
      but the rate of decay of postextrasystolic potentiation and the rate of
      relaxation of the twitch force were unaffected. CONCLUSIONS: These results
      suggest that the changes in the sensitivity of intact rat myocardium to [Ca2+]o
      and in maximum force development induced by cyclosporin are not due to changes in
      myofilament properties. The increased twitch force development as well as the
      spontaneous activity at low [Ca2+]o may be due to facilitated Ca2+ release from
      the sarcoplasmic reticulum due to altered properties of the sarcoplasmic
      reticular Ca2+ release channel, as both are observed when twitch force is
      submaximal, suggesting that the sarcoplasmic reticulum was not overloaded with
      Ca2+. The decline in peak stress with cyclosporin at [Ca2+]o > approximately 1.0
      mM can be explained on the basis of spontaneous release of Ca2+ during the
      interval between twitches which leaves less Ca2+ for release from the
      sarcoplasmic reticulum with each action potential.

PMID- 8275535
TI  - Characterisation and localisation of a 67 kDa calcium binding protein (p67)
      isolated from bovine hearts.
AB  - OBJECTIVE: A 67 kDa Ca2+ binding protein (p67) from bovine hearts has recently
      been purified. It bound Ca2+ in vitro and localised at the sarcolemma of both
      striated and smooth muscle cells. In this study, further biochemical and
      morphological experiments were carried out to examine whether the p67 is a member
      of the annexin family of proteins and how the protein is associated with the
      sarcolemma membrane. METHODS: Phospholipid and biological membrane binding assays
      were used to determine if p67 has the properties of the annexin family of
      proteins. Extraction experiments with Triton X-114 and Na2CO3 were carried out to
      examine potential association of p67 with sarcolemma membrane vesicles isolated
      from bovine hearts. For characterisation of the protein, actin binding assays and
      immunoelectron microscopy were performed. RESULTS: The p67 bound to acidic
      phospholipids and biological membranes in a Ca2+ dependent manner. The protein
      was exclusively recovered in the aqueous phase after Triton X-114 phase
      separation and it was released from sarcolemma membranes by Na2CO3 treatment. It
      bound to membrane cytoskeletons insoluble in Triton X-100 but failed to bind to F
      actin at physiological free Ca2+ concentrations. Immunoelectron microscopy showed
      that p67 seemed to be localised at the cytoplasmic side of the cardiac
      sarcolemma. CONCLUSION: The p67 that was purified from bovine hearts could be a
      member of the annexin family of proteins. It might be a peripheral membrane
      protein associated with the cytoplasmic side of sarcolemma membranes.

PMID- 8275536
TI  - Fluorocarbon simulation of myocardial ischaemia and reperfusion: studies of
      relationships between force and intracellular calcium.
AB  - OBJECTIVE: The aim was to compare the effects of simulated ischaemia-reperfusion
      with those of hypoxia-reoxygenation in isolated muscle preparations from the
      ferret right ventricle. METHODS: Ischaemia was simulated using fluorocarbon
      immersion plus hypoxia. Intracellular calcium transients were determined from
      aequorin luminescence during isometric contractions. RESULTS: Hypoxia in
      fluorocarbon and physiological saline solution resulted in a similar reversible
      depression of the peak of the calcium transient. Peak active tension, however,
      was more depressed in fluorocarbon than in physiological salt solution. The
      dissociation between peak light and peak active tension was most pronounced on
      reoxygenation, with near complete recovery of peak light, while there was little
      recovery of tension in fluorocarbon. When fluorocarbon was then replaced by
      physiological salt solution, peak active tension recovered promptly. A
      prolongation of the decay of the calcium transient was seen in both fluorocarbon
      and physiological salt solution during hypoxia, which shortened promptly on
      reoxygenation. The time to the peak of the calcium transient was most prolonged
      during hypoxia in fluorocarbon and there was gradual recovery on reoxygenation.
      CONCLUSIONS: While some changes in the calcium transient during simulated
      ischaemia are rapidly reversible with reoxygenation (in fluorocarbon), suggesting
      an effect of hypoxia, others are incompletely reversed or only reversed with
      physiological salt solution, suggesting an effect of metabolite accumulation. The
      pronounced dissociation between peak light and peak active tension during
      reoxygenation in fluorocarbon is promptly reversed by changing to physiological
      salt solution, suggesting that metabolite retention in the postischaemic period
      may contribute to depressed myocardial function after reperfusion.

PMID- 8275537
TI  - Alterations in cardiac myosin isozymes associated with aging and chronic
      hypertension: their modulation with nifedipine.
AB  - OBJECTIVE: Pressure induced left ventricular hypertrophy is associated with
      alterations in distribution of cardiac myosin isozymes. This study evaluated the
      influence of aging, superimposed chronic hypertension on aging, and treatment
      with nifedipine on cardiac myosin isozyme proportions. METHODS: Myosin isozyme
      (V1, V2, and V3) proportions were investigated by pyrophosphate gel
      electrophoresis, and left ventricular to body weight ratio was studied in two
      subgroups each of hypertensive and normotensive rats, with and without nifedipine
      treatment. Nifedipine treatment was started at 48 weeks and concluded at 60
      weeks. RESULTS: For all four groups, the V1 level was the lowest (range 15%-24%),
      V3 was the highest (47%-60%), and V2 was intermediate (25%-29%). The left
      ventricular weight to body weight ratio was 25% higher (p < 0.001) in the
      untreated old hypertensive v old rats, but V1 level was of the same magnitude in
      both these groups. The left ventricular weight to body weight ratio was 18% lower
      (p < 0.001) in the old hypertensive treated v untreated rats. The V1 level was
      higher in both treated groups; old normotensive as well as old hypertensive rats.
      The changes in V1 were not statistically correlated with arterial pressure and
      left ventricular to body weight ratio. CONCLUSIONS: The profound decrease in V1
      myosin isozyme proportion acquired with aging is not accentuated by superimposed
      chronic hypertension. The aging process, and not the left ventricular hypertrophy
      by itself, seems to be the principal determinant of the myosin isozyme shift. The
      myosin isozyme shift that occurs with aging is not fixed, and can be partially
      reversed or prevented by nifedipine.

PMID- 8275539
TI  - ATP-dependent potassium channel openers and preconditioning.

PMID- 8275538
TI  - Effect of extracellular ions and modulators of calcium transport on survival of
      tert-butyl hydroperoxide exposed cardiac myocytes.
AB  - OBJECTIVE: The aim was to investigate the effects of extracellular ions and
      agents that modify calcium translocating pathways on oxidative stress induced
      cell injury. METHODS: Survival of cardiac myocytes exposed to tert-butyl
      hydroperoxide (t-BHP, 0.2 to 2 mM) was estimated by their ability to maintain rod
      shaped morphology and exclude trypan blue, and by the release of lactate
      dehydrogenase (LDH). Mean life time (mu) of a myocyte was analysed in accordance
      with the Weibull distribution. RESULTS: In pCa 3.0 Ringer's solution, t-BHP
      exposed myocytes underwent time and concentration dependent hypercontracture. The
      fraction of rod shaped cells excluding trypan blue correlated with LDH release.
      The lifetime of a cell was increased upon reduction of [Ca]o. Myocytes exposed to
      t-BHP in pCa 7.0 or 8.0 Ringer's solution attained a rigor state and became
      permeable to trypan blue. t-BHP-induced hypercontracture was delayed on
      increasing [K]o or [Na]o. Reduction of [Na]o to 67.5 mM, but not to 13.5 mM,
      accelerated t-BHP induced hypercontracture. Early reduction of [Ca]o to a pCa of
      8.0 had no protective effect if 1 mM calcium was reintroduced after half the
      duration of exposure. Verapamil (10 microM), nifedipine (1 microM), butanedione
      monoxamine (20 mM), and caffeine (10 mM) accelerated t-BHP-induced loss of rod
      shaped morphology. Ryanodine (1 microM), Trolox-C (1 microM), and butylated
      hydroxytoluene (BHT, 500 microM) had no effect on survival of t-BHP exposed
      myocytes. Survival was prolonged upon preincubation of the myocytes with BAPTA-AM
      or desferrioxamine or when the cells were exposed to t-BHP in the presence of La
      (1 mM) or N-propyl gallate (10 microM). CONCLUSIONS: Ferrous catalysed free
      radical reactions initiated by t-BHP lead to hypercontracture or rigor shortening
      of myocytes, depending upon [Ca]o. It is unlikely that t-BHP-induced
      hypercontracture is mediated by Ca influx through L- or T-type Ca channels or due
      to release of Ca from intracellular stores. Activation of Ca influx via Na-Ca
      exchange and/or increase in the passive membrane permeability to Ca is consistent
      with the observations reported. Myocyte rigor observed upon attenuation of Ca
      overload suggests contribution of Ca-independent processes.

PMID- 8275540
TI  - ATP-dependent potassium channel openers and preconditioning.

PMID- 8275541
TI  - Na+/H+ exchange and regulation of intracellular Ca2+.

PMID- 8275542
TI  - Alpha 1 adrenergic stimulation, calcium, and arrhythmias.

PMID- 8275543
TI  - Influence of mold materials and heat treatment on tensile properties of Ni-Ti
      alloy castings.
AB  - The influence of mold materials and heat treatment on the tensile properties and
      the transformation temperatures of Ni-Ti alloy castings was investigated by
      tensile test and differential scanning calorimetry (DSC) in order to apply the
      special properties of the alloy to dental field. The compositions of the two
      alloys examined were 49.0 and 49.2 at % Ti. A silica investment and a magnesia
      investment were used as the mold materials. Heat treatment at 440 degrees C for
      1.8 ks was performed. Apparent proof strength decreased in both compositions, and
      residual strain increased in Ni-49.2Ti by the heat treatment. Elongation
      increased in Ni-49.0Ti with use of the magnesia mold or by the heat treatment.
      The transformation temperatures of Ni-49.2Ti increased with use of the magnesia
      mold. The change by the heat treatment suggested a structural change. The
      development of a suitable method for the casting of the alloy is expected to
      bring about the development of new devices and therapy in dentistry.

PMID- 8275544
TI  - The long term durability of bond strengths to dentin.
AB  - The aim of this study was to investigate the durability, throughout one year, of
      tensile bond strengths (TBS) to bovine dentin using various commercial and
      experimental bonding systems. Specimens were stored in a controlled solution of
      ion-exchanged water containing plaster chips and sodium azide. From the results
      it was concluded that the changes in TBS were not uniform over time, but a
      significant decrease was usually observed. For Super Bond D-liner and KB-100, the
      TBS were the highest and exhibited remarkable stability over the test period. The
      mode of fracture was noted to vary depending on the treatment system used, and
      was independent of TBS. Generally, the fracture mode tended to show increases in
      adhesive/cohesive failures within the resin over time. Super Bond D-liner always
      exhibited adhesive type failure at the tooth interface, and later involved
      failure in the hybrid layer. KB-100 showed very little change in failure over one
      year, being usually adhesive between bonding resin and resin composite. The
      results from this study indicate the need to carry out durability studies for the
      basic evaluation of all bonding systems. It was shown that the use of a
      controlled storage solution is important.

PMID- 8275545
TI  - Observations on structural features and characteristics of biological apatite
      crystals. 7. Observation on lattice imperfection of human tooth and bone crystals
      II.
AB  - In a series of studies to investigate the structural features of the biological
      crystal, such as the tooth and bone, using an electron microscope, we examined
      the ultrastructure of the human enamel, dentin, and bone crystals at near atomic
      resolution and showed the configuration of the hydroxyapatite structure through
      the cross and longitudinal sections of the enamel, dentin, and bone crystals.
      Subsequently, based on the results of our observations of the ultrastructure of
      the tooth and bone crystals, we attempted to clarify the essential structural
      features and characteristics of the lattice imperfections in the hydroxyapatite
      structure composing of the human enamel, dentin, and bone crystals from the
      morphological viewpoint. Therefore, using the same approach, we examined the
      images of the lattice imperfection of the normal human enamel, dentin, and bone
      crystals. In this report, following the previous observation of the lattice
      imperfection on the point defect structure and the dislocations appearing in the
      inner structure of the crystal, we describe the image of the face defect
      structure obtained by using the same approach from the sections of the human
      enamel, dentin, and bone crystals, such as the stacking fault, grain boundary,
      and others. The materials used for this study were the human enamel, dentin, and
      bone crystals. The small cubes of the material were fixed in glutaraldehyde and
      osmium tetroxide and embedded in epoxy resin using the routine methods. The
      ultrathin sections were cut with a diamond knife without decalcification. The
      sections were examined with the HITACHI H-800 H and H-9000 type transmission
      electron microscopes operated at 200 kV and 300 kV respectively. Each crystal was
      observed at an initial magnification of 300,000 times and at a final
      magnification of 10,000,000 times and over. We sincerely believe that the
      electron micrographs shown in this report are the first to show the images of the
      lattice imperfections from the sections obtained from the hydroxyapatite crystal
      composing of the human enamel, dentin, and bone tissue, such as the grain
      boundary, stacking fault, and others, at near atomic resolution.

PMID- 8275546
TI  - Observations on structural features and characteristics of biological apatite
      crystals. 8. Observation on fusion of human enamel crystals.
AB  - In a series of studies to investigate the basic structural features and
      characteristics of the biological apatite crystals, using a transmission electron
      microscope, we examined the ultrastructure of the human enamel, dentin, and bone
      crystals at near atomic resolution and showed the configuration of the
      hydroxyapatite structure through the cross and longitudinal sections of the
      crystals. Subsequently, based on the results of the observations by the authors
      of the ultrastructure of the tooth and bone, using the same approach, we have
      been able to directly examine the images of the lattice imperfections in the
      human tooth and bone crystals, such as the point defect structure, line defect,
      and face defect, in the crystals. In this report, we describe the images of the
      crystal fusion obtained by using the same approach from the sections of the human
      enamel crystals. The materials used for this study were the noncarious enamel
      from the freshly extracted human erupted lower first molars. The small cubes of
      the material were fixed in glutaraldehyde and osmium tetroxide and embedded in
      epoxy resin using the routine methods. The ultrathin sections were cut with a
      diamond knife without decalcification. The sections were examined with the
      HITACHI H-800 H and H-9000 type transmission electron microscopes operated at 200
      kV and 300 kV. Each crystal was observed at an initial magnification of 300,000
      times and at a final magnification of 10,000,000 times and over. We are,
      therefore, able to confirm that the fusion between the adjacent crystals can
      occur at some time during the life history of the human enamel. We sincerely
      believe that the electron micrographs shown in this report are the first to show
      the ultrastructures of the crystal fusion in the human enamel crystals at near
      atomic resolution.

PMID- 8275547
TI  - Stress of tooth and PDL structure created by bite force.
AB  - Stress is created by the bite force and distributed along the tooth towards the
      PDL structure. It is of interest to investigate the complex tooth structure,
      consisting of enamel, dentine, pulp, and thin cementum layer and how it functions
      in stress distribution. This study was intended to analyze the role of the tooth
      and PDL structures in stress distribution, by using a three-dimensional finite
      element method. A mandibular first molar was constructed for the finite element
      model. The bite forces were measured by Pressensor, and these bite force values
      were programmed to load down upon the occlusal surface of the model. The results
      were expressed by stress contours and principal stress graphs. The stress was
      found to decrease as it distributed from the occlusal surface towards the
      cervical portion in the dentine and the pulp. In contrast, the stress, especially
      a compressive stress, increased gradually in the enamel layer in the lower half
      of the crown, in the same direction. It was apparent in displayed pattern of
      stress that the stress distributed outward towards the surrounding portion of the
      lower half of the crown. This resulted in a uniform magnitude of the principal
      stresses for all aspects of the mesial and distal roots. The stresses of both
      roots were generally compressive stress. When comparing the stress values of
      sampling points positioned between the root surfaces and the periphery of the PDL
      (the alveolar wall), all principal stresses for those of the PDL (periodontal
      ligament) were less than those of the root surfaces. These findings revealed that
      the PDL, the dentine, and the pulp functioned in cooperation in stress reduction;
      and the sequences of enamel, dentine, and pulp influenced the pattern of stress
      distribution. The different material properties of the tooth structure in
      sequence was considered a very important factor for stress reduction and for the
      pattern of stress distribution, especially in the root.

PMID- 8275548
TI  - Intracellular calcium mobilization is triggered by clustering of membrane
      glycoproteins in concanavalin A-stimulated platelets.
AB  - Stimulation of human platelets with concanavalin A resulted in a significant
      increase in the concentration of cytoplasmic free Ca2+. This effect was due to
      two different processes: Ca2+ mobilization from internal stores and Ca2+ influx
      from the extracellular medium. Kinetic analysis revealed that the release of Ca2+
      from internal storage sites occurred sooner than the opening of plasma membrane
      Ca2+ channels. The ability of concanavalin A to induce a sustained increase in
      cytoplasmic Ca2+ concentration was antagonized and reversed by methyl alpha-D
      mannopyranoside, demonstrating that it was promoted by the interaction of the
      lectin with cell surface glycoproteins. Succinyl-concanavalin A, a dimeric
      derivative of the lectin, that does not promote patching/capping of the receptor,
      was able to bind to the platelet surface, and antagonized the effects of native
      concanavalin A. In addition, succinyl-concanavalin A, per se, was unable to
      induce Ca2+ mobilization in human platelets. Therefore, the action of the native
      concanavalin A was mediated by receptor clustering events. Concanavalin A
      mobilized Ca2+ from the same internal stores from which Ca2+ was mobilized in
      response to strong platelet agonists, such as thrombin and arachidonic acid.
      However, while thrombin was ineffective in inducing Ca2+ release after
      stimulation of platelets with ConA, ConA was able to cause a full discharge of
      Ca2+ from internal stores even in platelets previously stimulated with thrombin.
      These results demonstrate for the first time that the clustering of specific
      membrane glycoproteins can trigger platelet activation. The physiological
      implications during platelet aggregation are discussed.

PMID- 8275549
TI  - Thioglycollate stimulus modifies lymphocyte metabolism and proliferation. A
      comparison with lymphocyte activation by Walker 256 tumour implantation.
AB  - Key enzyme activities of glycolysis, the pentose-phosphate pathway, the Krebs'
      cycle and glutaminolysis were measured in lymphocytes obtained from the control
      (CC), thioglycollate-injected (TG) and Walker 256 tumour-implanted (WT) groups,
      non-immune and immune inflammatory stimuli, respectively. The rates of
      incorporation of [2-14C]-thymidine and [5-3H]-uridine into cultured lymphocytes
      were also determined. The results indicated that the rates of both [2-14C]
      thymidine and [5-3H]-uridine incorporation were enhanced in lymphocytes obtained
      from thioglycollate-injected (by an average of 80 per cent) and tumour-implanted
      animals (by 2.4-fold) as compared to control rats. Lymphocyte hexokinase activity
      diminished both in the TG (23 per cent) and WT (61 per cent) groups, whereas
      glucose 6-phosphate dehydrogenase activity was not altered due to the non-immune
      inflammatory stimulus, being reduced (23 per cent) in WT rats as compared to CC.
      The activity of lymphocyte citrate synthase was lowered by thioglycollate (39 per
      cent) and tumour-implantation (46 per cent). In contrast, glutaminase activity
      was augmented in lymphocytes from the TG (41 per cent) and was not modified in
      the WT groups. Taken as a whole, the presence of the Walker 256 tumour did not
      affect the capacity for glutamine utilization but depressed glucose metabolism in
      these cells. On the other hand, the non-immune inflammatory stimulus suppressed
      the activities of glycolysis and the Krebs' cycle and enhanced that of
      glutaminolysis in lymphocytes.

PMID- 8275550
TI  - PTH induces modification of transductive events in otosclerotic bone cell
      cultures.
AB  - We studied the effect of PTH (10-100 nM) on transductive mechanisms (adenylate
      cyclase activity, Ca2+ metabolism, IP3 levels) in cell cultures derived from
      normal and otosclerotic human bone fragments. The cultured cells were osteoblast
      like but with calcitonin-receptors still present and with PTH receptors coupled
      with the adenylate cyclase system. The results showed that PTH activated
      adenylate cyclase and increased the intracellular Ca2+ levels with qualitative
      and quantitative differences between the two cellular populations. In particular,
      otosclerotic cells responded less to hormone stimulation, which is in accord with
      the current hypothesis of a desensitization of the receptor/enzyme complex
      associated with the pathological status.

PMID- 8275551
TI  - Modifications of proteoglycans produced by human skin fibroblast cultures during
      replicative senescence.
AB  - The properties of proteoglycans (PGs) produced by normal human skin fibroblasts
      were investigated with increasing passage. The increase of subculture number was
      associated with a constant increase in PG molecular size, which was particularly
      evident in cell layer extracts. In the cell layer, the ratio of DS-PGs/HS-PGs was
      markedly higher in early passage cultures. Moreover, the cell layer from young
      cells contained lower amounts of radioactivity incorporated into the most
      hydrophobic PG populations, suggesting that the PG core protein might also
      undergo significant modification with increasing subcultures. There was no
      significant difference in energy charge value between early and late passage
      cultures, whereas the NAD/NADH ratio was found to decrease markedly in senescent
      cells.

PMID- 8275552
TI  - Characterization of over-expressed alkaline phosphodiesterase I in tumour-derived
      fibroblasts from patients with neurofibromatosis.
AB  - Alkaline phosphodiesterase I from cultured fibroblasts from patients with
      neurofibromatosis was partially purified and characterized following extraction
      with Triton X-100, and fractionation with high-performance liquid chromatography.
      Some properties were compared with the enzyme extracted from normal-appearing
      fibroblasts. The isoelectric points of both the tumour and normal-appearing cell
      enzymes were 6.0. The enzyme required Zn2+ for its activity, was heat labile, and
      nicked superhelical covalently closed circular phi X174 DNA. The activity was
      inhibited by GTP, DTT and EDTA. The native molecular weight of alkaline
      phosphodiesterase I was determined to be 430,000. No differences were found in
      properties of the tumour-derived and normal cell enzymes. On purification it was
      observed that the peak pattern of enzyme activity corresponded to that of 125 kDa
      protein, which was more abundant upon SDS-PAGE analysis in tumour cells than in
      normal cells. The most active fraction of isoelectric focusing, which was
      performed using disulfide cross-linked polyacrylamide gel, was used to produce an
      antibody. The bands of 125, 60 and 40 kDa were immuno-stained in tumour cell
      preparation. These results indicate that alkaline phosphodiesterase I, of which
      the molecular weight is probably 125 kDa, is over-expressed in tumour-derived
      fibroblasts from neurofibromatosis patients.

PMID- 8275553
TI  - Stimulation of HeLa cell growth by physiological concentrations of 4
      hydroxynonenal.
AB  - The aim of this study was to analyze the growth response of HeLa cells over a
      prolonged period of time to a single exposure of physiological and
      supraphysiological concentrations of 4-hydroxynonenal (HNE), a peroxidation
      product of omega-6-polyunsaturated fatty acids. Furthermore, the growth
      modulating effect of serum factors, particularly albumin, on the growth pattern
      was examined. The effects of HNE on the growth rate and viability of the cells,
      as well as on the incorporation of labelled amino acids were monitored daily over
      a period of four days. Fetal calf serum not only had a growth stimulating effect
      but also modulated the action of HNE. In neither respect was albumin able to
      substitute for serum indicating that the influence of serum was not exerted via
      an albumin-HNE conjugate. HNE had a clear dose-dependent effect and a distinction
      could be made between a supraphysiological concentration (100 microM), which was
      primarily cytotoxic and a physiological range (below 10 microM) which showed
      growth modulatory effects. These effects consisted of a transient inhibition in
      the initial phase of the cell growth, which under optimal conditions (in presence
      of serum) was followed by a period of increased proliferation, compared to
      untreated control cultures, until confluence was attained. It is suggested that
      HNE is not only a toxic product of lipid peroxidation, but a physiological growth
      regulating factor as well.

PMID- 8275554
TI  - On the association of DNA primase activity with the nuclear matrix in HeLa S3
      cells.
AB  - We have reinvestigated the association of DNA primase activity with the nuclear
      matrix prepared from exponentially growing HeLa S3 cells. We have found that 25
      30 per cent of the nuclear primase activity resists extraction with 2 M NaCl and
      digestion with Dnase I. Unlike previous investigations, done with the same cell
      line, the results showed that nuclear matrix-bound DNA primase activity
      represented less than 10 per cent of the total cell activity. Association of high
      levels of primase activity with the nuclear matrix was strictly dependent on a 37
      degrees C incubation of isolated nuclei prior to subfractionation. Evidence was
      obtained that the method used for preparing nuclei can have a dramatic effect on
      the amount of primase activity which is recovered both in the postnuclear
      supernatant and in isolated nuclei, thus seriously affecting the interpretation
      of the results about the quantity of DNA primase activity bound to the nuclear
      matrix.

PMID- 8275555
TI  - The Shock Society membership directory.

PMID- 8275556
TI  - Prenatal screening for cystic fibrosis: attitudes and responses of participants.
AB  - A screening programme to detect cystic fibrosis heterozygotes has been running in
      the antenatal clinics of a major Edinburgh maternity hospital for more than 2
      years. A questionnaire was used to assess participants' knowledge of the genetics
      of the disorder and their attitudes to being screened. The respondents were 64
      female heterozygotes and 63 of their non-heterozygous male partners, 101 female
      controls and 100 male controls. Although the two groups of controls received far
      less direct information than the carriers and their partners, all four groups
      were well informed about the genetics of cystic fibrosis and the significance of
      being a gene carrier. A majority of each group felt that adequate information had
      been given in the information leaflet, that they understood the purpose of
      screening and that they were glad to have participated. There was a consensus
      that CF carrier testing should be routinely offered to pregnant women, and also
      that it should be available in family planning clinics and GP health centres, but
      not in schools.

PMID- 8275557
TI  - Ridge hypoplasia and ridge dissociation: minor physical anomalies in autistic
      children.

PMID- 8275558
TI  - 46XY/47XYY mosaicism and fragile X.

PMID- 8275559
TI  - Short report on DNA marker at candidate locus.

PMID- 8275560
TI  - Parental origin of the supernumerary chromosome in trisomy 18.
AB  - The parental origin of an extra chromosome in Edwards syndrome has been
      investigated in 23 families by the combination of the VNTR probe pERT25, two
      microsatellite polymorphisms for D18S34 and D18S40, and several two-allele
      polymorphisms. Of the 23 cases, 22 were informative, with 17 (77%) being maternal
      and 5 (23%) paternal in origin. These results support the previous
      investigations, suggesting that trisomy 18 is predominantly of maternal origin,
      although a higher rate of paternally derived cases was observed than previously
      reported. A significant increase in maternal age was found to be associated with
      meiotic nondisjunction. Parental age was increased in both the maternally and
      paternally derived cases, but the size of the latter class was small and did not
      reach statistical significance.

PMID- 8275561
TI  - Retinitis pigmentosa: problems associated with genetic classification.
AB  - Genetic classification of retinitis pigmentosa (RP) can be problematic, due to a
      large number of isolated cases, reduced penetrance, and considerable variation in
      expressivity. Another confounder is a high proportion of affected female carriers
      in X-linked RP. Based on the genetic definitions of five different authors, a
      reclassification experiment was conducted with 350 Danish families. Agreement
      existed about a small "nucleus" of familial cases. Most definitions favored
      autosomal dominant inheritance at the expense of X-linked. The experiment
      revealed that methodological differences to a large extent might explain the
      considerable variation among reported genetic frequencies of retinitis
      pigmentosa.

PMID- 8275562
TI  - Infertility in carriers of two bisatellited marker chromosomes.
AB  - Two unrelated sterile patients, a male and a female, with karyotypes
      characterized by the presence of two supernumerary bisatellited marker
      chromosomes, were studied with the aid of fluorescence in situ hybridization
      (FISH). Using alphoid centromeric specific probes, the markers were identified as
      an idic (15) (pter-q11) and a mar (14). In both cases a single accessory
      bisatellited marker was present in the karyotype of one of the parents. A
      possible correlation between the excess of constitutive heterochromatin and
      meiotic disturbances in the two patients is discussed.

PMID- 8275563
TI  - Association of Shokeir syndrome (congenital universal alopecia, epilepsy, mental
      subnormality and pyorrhea) and giant pigmented nevus.
AB  - The second case of Shokeir syndrome (congenital total permanent alopecia,
      psychomotor epilepsy, mental retardation and pyorrhea) is described in a
      Hungarian boy. This syndrome was associated with a giant pigmented nevus in this
      case.

PMID- 8275564
TI  - Slipped capital femoral epiphysis associated with Rubinstein-Taybi syndrome.
AB  - The association of Rubinstein-Taybi syndrome (RTS) and slipped capital femoral
      epiphysis (SCFE) is described in a girl aged 9 years and 10 months. SCFE has
      never been reported associated with RTS, neither as an isolated anomaly, nor in a
      familial pedigree. However, a "stiff gait" is frequently described in RTS
      patients and, furthermore, obesity is a frequent feature of RTS patients. Some
      reports in the literature suggest the need for an early diagnosis of SCFE among
      adolescent relatives of patients with SCFE. Since many SCFEs are asymptomatic and
      an early diagnosis is essential for a favorable prognosis, we suggest an annual
      echotomographic or radiological examination of the hips in RTS patients.

PMID- 8275565
TI  - Effect of the fragile X anomaly on body proportions estimated by pedigree
      analysis.
AB  - The purpose of this study was to determine the effect of the fragile X syndrome
      on limb (upper limb length) and facial (ear length) measurements in relation to
      body height, which was considered as a covariate. The analysis was performed in
      52 fragile X Caucasian families, including affected individuals as well as their
      normal relatives. The maximum likelihood analysis of complex pedigrees, under the
      assumption of multivariate normality, was used to select the best genetic model
      and to estimate model parameters. This method allowed us to test various
      assumptions concerning the effect of normal hereditary variation, as well as of
      genetic anomaly and other relevant factors, in the mean and variance of a
      quantitative trait, and to obtain the maximum likelihood parameters for these
      effects. The results demonstrated that, if the family factor is accounted for in
      a model, the fragile X condition affects growth of both upper limb length and ear
      length, disproportionately to body height.

PMID- 8275567
TI  - Kaufman oculocerebrofacial syndrome: report of two new cases and further
      delineation.
AB  - Two unrelated Mexican girls, aged 14 months and 6 years respectively, with
      Kaufman oculocerebrofacial syndrome, are reported. Both showed psychomotor
      retardation, microcephaly, blepharophimosis and delayed growth as the main
      features; the infant also presented preauricular tags and large clitoris.
      Comparative analysis with previous cases reveals a heterogeneous syndrome in
      which the micro-brachycephaly, the mongoloid slanted eyes with different
      anomalies, the micrognathia and the neonatal respiratory distress are the most
      typical characteristics of this mental retardation syndrome.

PMID- 8275566
TI  - Frontonasal dysplasia, lipoma of the corpus callosum and tetralogy of Fallot.
AB  - A 6-year-old Egyptian boy with frontonasal dysplasia (FND) and lipoma of the
      corpus callosum associated with tetralogy of Fallot is reported. The main
      features were severe hypertelorism, downward slanted palpebral fissures,
      bilateral epicanthal folds, a grossly deformed nose with notched alae nasi,
      absent nasal tip and long philtrum. A computerized tomography (CT) scan of the
      brain showed cerebral atrophy and lipoma of the corpus callosum. While marked
      neurological symptoms have been reported in cases with lipoma of the corpus
      callosum in the absence of FND, the present case and previous reports showed
      minor neurological alterations when lipoma of the corpus callosum was associated
      with FND. From the findings in this case and previous reports, it is possible to
      conclude that lipoma of the corpus callosum associated with FND is always located
      in the anterior part of the corpus callosum. The etiology of FND remains
      uncertain. While multifactorial inheritance has been proposed, parental
      consanguinity with young parental age in the present case cannot exclude
      autosomal recessive inheritance.

PMID- 8275568
TI  - DNA polymorphisms of the apolipoprotein B gene are associated with obesity and
      serum lipids in healthy Indians in Singapore.
AB  - Three DNA polymorphisms (Ins/Del, XbaI and EcoRI) of the apolipoprotein B gene
      and their influence on body-mass index, serum lipids and apolipoprotein levels
      were studied in 181 healthy Indians of both sexes (121 males and 60 females),
      aged between 17 and 71 years. The frequencies of X+ (XbaI) and Del (Ins/Del) of
      the signal peptide region in Indians were found to be significantly lower (0.17
      and 0.11, respectively) compared to the frequencies in Caucasians (0.50 and 0.32,
      respectively) (P < 0.025). The frequency of E- (EcoRI) was similar to that in
      Caucasians (0.10 vs 0.15). A highly significant linkage disequilibrium was
      observed between the XbaI site and Ins/Del polymorphism of the apo B gene in this
      sample (X2 = 31.9, P < 0.001). The simultaneous presence of Del and X+ allele was
      significantly associated with higher body mass index (X2 = 11.43, P < 0.005),
      serum total cholesterol (X2 = 5.11; P < 0.025) and triglyceride (X2 = 6.42; P <
      0.025) levels. Mean values of adjusted BMI and serum triglyceride levels were
      found to be 29.0 +/- 1.92 vs 23.7 +/- 0.67 (P < 0.025) and 278.0 +/- 60.78 vs
      140.4 +/- 15.43 mg/dl (P < 0.05), respectively, in subjects with Del and X+
      compared to others. The multiple regression tests showed that 3.3 and 5.8% of the
      total variability of BMI is explained by Ins/Del and XbaI polymorphism,
      respectively, in this sample (P = 0.06 and 0.02), while 3.8% of serum
      triglyceride levels was explained by Ins/Del polymorphism of the apo B gene (P =
      0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275569
TI  - Ambras syndrome: delineation of a unique hypertrichosis universalis congenita and
      association with a balanced pericentric inversion (8) (p11.2; q22)
AB  - Congenital hypertrichosis universalis is a rare autosomal dominant disease. We
      report the further development of a Greek girl, now aged 3 years, the first case
      associated with a balanced structural chromosomal aberration. She was described
      as a neonate by Sigalas et al. (1990). Her persistent generalized hypertrichosis
      is most excessive on the face, ears and shoulders. Her fine silky hair is of the
      vellus, not the lanugo type. The syndrome features are characterized, referring
      to nine further published case reports. It is distinguished from other types of
      congenital hypertrichoses, which have been described in the literature under
      different synonyms. To avoid confusion in the terminology, we propose to name
      this type of hypertrichosis Ambras syndrome in reference to the first documented
      family with congenital hypertrichosis universalis in the 16th century.

PMID- 8275570
TI  - Anthropometric and craniofacial patterns in mentally retarded males with emphasis
      on the fragile X syndrome.
AB  - Anthropometric and craniofacial profile patterns indicating the percent
      difference from the overall mean were developed on 34 physical parameters with 31
      white, mentally retarded males (23 adults and 8 children) with the fra(X)
      syndrome matched for age with 31 white, mentally retarded males without a known
      cause of their retardation. The fra(X) syndrome males consistently showed larger
      dimensions for all anthropometric variables, with significant differences for
      height, sitting height, arm span, hand length, middle finger length, hand
      breadth, foot length, foot breadth, and testicular volume. A craniofacial pattern
      did emerge between the two groups of mentally retarded males, but with overlap of
      several variables. Significant differences were noted for head circumference,
      head breadth, lower face height, bizygomatic diameter, inner canthal distance,
      ear length and ear width, with the fra(X) syndrome males having larger head
      dimensions (head circumference, head breadth, head length, face height and lower
      face height), but smaller measurements for minimal frontal diameter, bizygomatic
      diameter, bigonial diameter, and inner canthal distance. Several significant
      correlations were found with the variables for both mentally retarded males with
      and without the fra(X) syndrome. In a combined anthropometric and craniofacial
      profile of 19 variables comparing 26 white fra(X) syndrome males (13 with high
      expression (> 30%) and 13 with low expression (< 30%), but matched for age), a
      relatively flat profile was observed with no significant differences for any of
      the variables. Generally, fra(X) syndrome males with increased fragile X
      chromosome expression have larger amplifications of the CGG trinucleotide repeat
      of the FMR-1 gene. No physical differences were detectable in our study between
      fra(X) males with high expression and apparently larger amplifications of the CGG
      trinucleotide repeats compared with those patients with low expression. Our
      research illustrates the use of anthropometry in identifying differences between
      mentally retarded males with or without the fra(X) syndrome and offers a
      comprehensive approach for screening males for the fra(X) syndrome and selecting
      those individuals for cytogenetic and/or molecular genetic testing.

PMID- 8275571
TI  - Prenatal detection of an inverted X chromosome in a male.
AB  - An unusual case of an X chromosome with a pericentric inversion (p11.3q21.3) was
      detected prenatally in a male fetus. This inversion has not been previously
      characterized. Although the inverted chromosome was transmitted through the
      mother, no living males on the maternal side were detected with the aberrant
      chromosome. Replication studies were performed on cultures of maternal peripheral
      blood lymphocytes, and it was determined that the inverted X chromosome was early
      replicating in approximately half of the cells. Following genetic counseling, the
      pregnancy was continued and a healthy male infant was delivered at term.
      Cytogenetic analysis of peripheral blood performed in the newborn period
      confirmed the prenatal findings. The child is developing normally at 3 years of
      age.

PMID- 8275572
TI  - Y chromosome mosaicism in the gonads, but not in the blood, of a girl with the
      Turner phenotype and virilized external genitalia.
AB  - We describe a girl with virilized external genitalia and phenotypic features of
      Turner syndrome whose blood karyotype is 45,X. The presence of dysgenetic
      testicular tissue was confirmed by pathology. Using PCR and primers for the
      distal long arm, centromere and short arm of the Y chromosome, Y chromosome
      material was detected in her gonads but not in blood.

PMID- 8275573
TI  - MCA/MR syndrome with features of Hallermann-Streiff syndrome and 4q
      deficiency/14q duplication.
AB  - In this report we present the clinical history and findings in a female newborn
      with 4q deficiency/14q duplication, the unbalanced product of a paternal
      t(4;14)(q33;q32). The clinical symptoms and signs observed in this child up to
      the age of 14 months were most compatible with the diagnosis of Hallermann
      Streiff syndrome.

PMID- 8275574
TI  - Further evidence for the location of the blepharophimosis syndrome (BPES) at
      3q22.3-q23.
AB  - We report a 6-year-old, mentally retarded boy with typical clinical signs and
      symptoms of the blepharophimosis syndrome (blepharophimosis, ptosis, epicanthus
      inversus syndrome (BPES)), born to normal parents. Chromosome studies revealed an
      interstitial deletion in the long arm of chromosome 3: del(3)(q22.3-->q23). This
      observation reinforces previous suggestions that the location of the BPES gene is
      at 3q2, i.e. 3q22.3-q23.

PMID- 8275575
TI  - Progressive pseudorheumatoid arthritis of childhood (PPAC) and normal adult
      height.
AB  - Two brothers and a sister presented with spondyloepiphyseal dysplasia and
      progressive arthropathy. Stiffness and restricted mobility of several large
      joints had been present since childhood. Their adult height was normal, and
      skeletal radiography showed mild platyspondyly, abnormal epiphyses and severe
      osteoarthrosis with extensive synovial osteochondromatosis. This autosomal
      recessive type of spondyloepiphyseal dysplasia tarda must be distinguished from
      other forms of spondyloepiphyseal dysplasia, rheumatoid arthritis in childhood
      and osteoarthrosis in adults.

PMID- 8275576
TI  - Molecular cytogenetic analysis of a familial pericentric inversion of chromosome
      12.
AB  - We describe the application of multi-color fluorescence in situ hybridization
      (FISH) in the characterization of a familial pericentric inversion. Using
      chromosome 12 short- and long-arm specific DNA probes, fast and reliable
      discrimination between normal and inversion chromosome 12 or recombinant
      inversion chromosome 12 was possible. FISH thus provides a reliable means for
      prenatal detection of balanced or unbalanced chromosome 12 rearrangements in this
      family. This approach is possible for identification of similar chromosome
      rearrangements provided that probes for the putatively involved chromosome region
      are available.

PMID- 8275577
TI  - Bilateral vocal cord paralysis in Williams syndrome.
AB  - Williams syndrome was first described in 1961 (Williams et al. 1961) and is a
      well-recognised clinical syndrome characterised by growth deficiency, learning
      difficulties and a typical facies. We describe a 9-year-old girl with classical
      features of Williams syndrome who presented with acute vocal cord paralysis for
      which no other cause was found.

PMID- 8275578
TI  - Case of human chimerism detected by unbalanced chromosome translocation?

PMID- 8275579
TI  - De novo DNA rearrangement in atypical facioscapulohumeral muscular dystrophy.

PMID- 8275580
TI  - Hypertension and the antiphospholipid antibodies.

PMID- 8275581
TI  - Use of the Stoke Index to differentiate between disease-modifying agents and non
      steroidal anti-inflammatory drugs in rheumatoid arthritis.
AB  - The Stoke Index is a validated composite algorithm that has been designed to give
      a global measure of disease activity in rheumatoid arthritis (RA). The use of
      this single measure of disease activity in RA simplifies the critical evaluation
      of drug therapy. 368 patients with RA of varying duration and severity, entered
      into comparative drug trials between 1980 and 1987, had the algorithm calculated
      four weeks prior to therapy, at the start of treatment, and bi-monthly to six
      months. The index score was significantly improved by drugs with known slow
      acting anti-rheumatic drug (SAARD) activity and improvement could be seen as
      early as two months after the beginning of treatment. Non-steroidal anti
      inflammatory drugs (NSAIDs) did not improve the score. The index differentiates
      between treatments in patients with minor or major disease activity. We conclude
      that this composite index of disease activity provides a sensitive, meaningful
      measure for the evaluation of therapy in RA.

PMID- 8275582
TI  - Malignant hypertension in antiphospholipid syndrome without overt lupus
      nephritis.
AB  - The antiphospholipid syndrome is usually defined by the association of a clinical
      manifestation (recurrent venous and/or arterial thrombosis, recurrent spontaneous
      miscarriages) and a biological abnormality (anticardiolipin antibody, lupus
      anticoagulant). We retrospectively analyzed the records of 5 patients (4 females,
      1 male, aged 30 +/- 12 years) with antiphospholipid syndrome, primary (n = 1) or
      secondary to systemic lupus erythematosus (n = 4), who developed malignant
      systemic hypertension with renal insufficiency, in the absence of lupus
      nephritis. Before the episode of malignant hypertension, all patients had normal
      systemic blood pressure and renal function. During malignant hypertension the
      systolic pressure was 206 +/- 39 mmHg and the diastolic pressure 130 +/- 25 mmHg,
      peak serum creatinine was 204 +/- 95 mumol/l, daily proteinuria was 1.1 +/- 0.8
      gr, and complement serum levels were normal in all patients. Renal angiography
      found normal proximal renal arteries. Renal biopsy showed ischaemic glomeruli
      without proliferative lesions (n = 5), focal intimal fibrosis either isolated (n
      = 3) or associated with thrombosis (n = 2) of the intrarenal vessels, and the
      absence of vasculitis. Immunofluorescence study did not reveal typical lupus
      deposits. Patients were treated with antihypertensive agents, increasing doses of
      prednisone (n = 3), and anticoagulant (n = 2) or anti-aggregant therapy (n = 1).
      After a mean follow-up of 6.8 +/- 5.2 years, 4 patients were still alive with
      normal blood pressure and renal function, whereas 1 patient died of a probable
      catastrophic antiphospholipid syndrome. Patients with antiphospholipid syndrome,
      primary or secondary to systemic lupus erythematosus, may develop malignant
      hypertension with renal insufficiency and intrarenal vascular lesions, in the
      absence of lupus nephritis.

PMID- 8275583
TI  - Treatment of the cutaneous lesions of systemic lupus erythematosus with
      thalidomide.
AB  - Twenty three patients with SLE and cutaneous lesions not responsive to
      chloroquine, photoprotectors and corticosteroid in doses < 0.5 mg/kg/day were
      treated with thalidomide 300 mg/day. Three patients presented side effects and
      had to discontinue treatment. Eighteen of the remaining 20 patients (90%) had
      complete remission of the cutaneous lesions and 2 had partial improvement.
      Another important parameter of improvement was a reduction in the average
      prednisone dose required from 40.5 mg/day to 17.4 mg/day. The most frequent side
      effects were drowsiness in 52% of cases and abdominal distention in 22%. These
      symptoms were reversed by dose reductions in all but one patient. Thalidomide was
      shown to be efficient in the treatment of cutaneous lesions unresponsive to more
      usual treatments.

PMID- 8275584
TI  - Severity of rheumatoid arthritis, function and quality of life: sub-group
      comparisons.
AB  - The main purpose of this study was to explore whether people with more severe
      rheumatoid arthritis, as diagnosed by increasing functional disability, also
      exhibit a poorer quality of life, being more negatively affected by the disease,
      than individuals with less severe rheumatoid arthritis. A cross-sectional survey
      was carried out on 169 females and 53 males with rheumatoid arthritis (RA).
      Functional status was measured according to the Stanford Health Assessment
      Questionnaire (HAQ), overall ill-health was assessed by the Sickness Impact
      Profile (SIP) and the quality of life assessment was performed using a generic
      quality of life assessment package (QLsc). The severity of RA, as measured by
      HAQ, correlated both with changes due to disease and the quality of life status,
      and with SIP. The intrusion of the disease appeared to be greatest within the
      physical life domain, followed by the psychological and social domains.
      Correlations between the physical, psychological and social life domains were
      high. Although the relationship between the various life domains is complex, the
      present study confirms a significant relation between physical and psycho-social
      dysfunction.

PMID- 8275585
TI  - Down-regulation by eel calcitonin of interleukin-1 release and production by
      peripheral blood monocytes from patients with rheumatoid arthritis.
AB  - To clarify the reason for the therapeutic efficacy of Elcatonin (eCT), an eel
      calcitonin derivative, in rheumatoid arthritis (RA), we studied the effect of eCT
      on the extracellular (EC) release and intracellular (IC) production of
      interleukin-1 (IL-1) by peripheral blood monocytes from patients with RA. In
      vitro treatment of RA monocytes with eCT reduced predominantly the EC release of
      both IL-1 alpha and IL-1 beta. Moreover, EC release and IC production of IL-1
      alpha and IL-1 beta by monocytes from RA patients who received non-steroidal anti
      inflammatory drugs (NSAIDs) plus eCT (CT group) were significantly lower than in
      those who received NSAIDs only (NSAID group). The anti-rheumatic effect of eCT
      may be mediated via the inhibition of EC release and the IC production of IL-1
      from RA patients.

PMID- 8275586
TI  - The effect of D-penicillamine on lung function parameters (diffusion capacity) in
      rheumatoid arthritis.
AB  - Sequential lung function tests were performed on 28 rheumatoid arthritis (RA)
      patients who were treated with D-penicillamine (total of 101 treatment years) and
      on 42 control RA patients who were not treated or who were treated with NSAIDs,
      chloroquine, gold salts, corticosteroids, salazopyrine or methotrexate. A decline
      in lung function parameters was found in both groups, although it was only
      significant for the carbon monoxide diffusing capacity corrected for lung volume
      (DLCO/VL). This decrease in DLCO/VL was less pronounced in the D-penicillamine
      group (mean -6.9%) than in the control group (mean -11.3%). This difference could
      not be attributed to smoking, which was more frequent in the control group. When
      reviewing only the patients with an initial DLCO/VL < 80% of the predicted value
      and having, with some exceptions, chest X-ray abnormalities, we even observed an
      amelioration in the mean DLCO/VL in the D-penicillamine group, in contrast with a
      deterioration in the control group (+5.1% versus -5.6%).

PMID- 8275587
TI  - Neutralization of interleukin-1 beta activity in vivo with a monoclonal antibody
      alleviates collagen-induced arthritis in DBA/1 mice and prevents the associated
      acute-phase response.
AB  - Interleukin-1 (IL-1) has been implicated in the development and progression of a
      variety of acute and chronic inflammatory diseases. Due to its pro-inflammatory
      and tissue-degrading activities, IL-1 is regarded as a major mediator of chronic
      inflammatory joint diseases, including rheumatoid arthritis in man, adjuvant
      arthritis in rats and collagen-induced arthritis in mice. However, conclusive
      experimental evidence for the crucial role of IL-1 in the development of joint
      destruction has not been presented as yet. In the present study, we investigated
      the effect of a neutralizing monoclonal mouse antibody against mouse IL-1 beta
      (IgG1 isotype) on the development and progression of collagen-induced arthritis
      in DBA/1 mice. The antibody was injected intraperitoneally 3 times a week, either
      from day 3 or from day 21 after primary immunization, to day 60. In the positive
      control group an arthritis incidence of 80% was observed after 60 days. The
      injection of a control antibody of the same isotype did not influence the
      incidence of arthritis, whereas injection of anti-IL-1 beta from day 21 reduced
      the arthritis incidence to about 30%. Injection of anti-IL-1 beta starting at day
      3 totally prevented both the development of arthritis and the associated increase
      of the acute phase protein serum amyloid P (SAP). Anti-collagen antibody titers,
      which increased significantly after immunization, were not influenced by the
      injection of anti-IL-1 beta antibodies, in spite of the suppressive effect on
      arthritis development.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275588
TI  - Reappraisal of tests for xerostomia.
AB  - Our goal was to establish the practical usefulness of combinations of tests
      (saliva flow rate, SFR; salivary lysozyme, Lys; salivary lactoferrin, Lf;
      sialography, SG; salivary gland scintigraphy, SGS; and labial salivary gland
      biopsy, SGB) for the oral component of Sjogren's syndrome (SS). These tests were
      applied to 40 patients with primary SS (group A, defined by the presence of
      keratoconjunctivitis sicca, a positive response to two of three selected
      questions for xerostomia and the presence of two of four autoantibodies), 16
      patients with secondary SS (group B), 16 patients with connective tissue disease
      but no evidence of secondary SS (group C) and 14 normal controls (to establish
      the threshold of the six tests). SFR was decreased in 68, 56 and 19% of the
      patients in groups A-C respectively [sensitivity (sens) 68%, specificity (sp)
      81%, positive predictive value (PPV) 90% and negative predictive value (NPV) 50%
      for primary SS]. Lys was elevated in 3, 0 and 0% of the patients in groups A-C
      (sens 3%, sp 100%, PPV 100% and NPV 66%). Lf was reduced in 58, 69 and 25% of the
      patients in groups A-C (sens 58%, sp 75%, PPV 82% and NPV 53%). SG was positive
      in 74, 27 and 13% of the patients (sens 74%, sp 87%, PPV 93% and NPV 41%). SGS
      was positive in 75, 63 and 25% of the patients (sens 75%, sp 75%, PPV90% and NPV
      45%). SGB was abnormal in 95, 94 and 25% (sens 95%, sp 75%, PPV 90%, NPV
      14%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275589
TI  - Immunogenetics of polymyalgia rheumatica.
AB  - The distribution of HLA-D region antigens was studied in 17 patients with well
      documented polymyalgia rheumatica (PMR). HLA-D region antigens were defined by
      the oligonucleotide typing of polymerase chain reaction (PCR)-amplified genomic
      DNA. The results demonstrate that the prevalence of DR4 was significantly higher
      (p < 0.0002; RR = 8.10) in patients (70.6%) compared to normal controls (22.9%),
      and the frequency of DR1 and/or DR4 in patients (82.4%) was also higher (p <
      0.0006; RR = 8.40) than that in normal healthy controls (35.7%). Of the subtypes
      of DR4,Dw13 was significantly higher (p < 0.002; RR = 9.30) in patients (29.4%)
      than in normal controls (4.3%). However, these data must still be confirmed by
      other investigators. The distribution of the remaining DR antigens and of the DQ
      and DP alleles in patients did not differ significantly from those in controls.
      The results suggest immunogenetic similarity between PMR and late onset
      rheumatoid arthritis in elderly populations.

PMID- 8275590
TI  - Serum levels of secretory IgA and in vitro production of IgA in rheumatoid
      arthritis.
AB  - Twenty-three per cent of rheumatoid arthritis (RA) patients show an increase of
      serum IgA concentrations. To determine the role of mucous-associated lymphoid
      tissue (MALT) in the elevation of serum IgA in RA, we studied the serum secretory
      IgA (s-IgA) in 63 RA patients and in 30 healthy controls. We also analysed the
      secretion of circulating B cells producing IgA, which is known to reflect mucous
      tissue activity, in a subgroup of 15 patients with increased serum IgA
      concentrations, and in control patients. The mean s-IgA in the RA patients was
      0.046 mg/ml +/- 0.064, versus 0.002 +/- 0.004 mg/ml in controls (not
      significant). Active disease defined by clinical criteria was associated with an
      increase in serum s-IgA (p < 0.001). Furthermore, in a subgroup of RA patients
      with high serum IgA levels, we found an increase in in vitro IgA production by
      circulating blood lymphocytes (17.39 +/- 15.2 micrograms/ml), versus RA patients
      with normal serum IgA levels or controls (p < 0.001). These results were not
      modified by LPS or PWM. Our results further support the hypothesis of primary
      MALT activation following environmental antigenic stimulation in RA patients.

PMID- 8275591
TI  - Scleromyxedema associated with arthritis and myopathy: a case report.
AB  - Herein we report a patient with scleromyxedema associated with seronegative
      polyarthritis and proximal myopathy. The histopathologic and electron microscopic
      features are described and compared with previously reported patients with
      documented scleromyxedema and myopathy.

PMID- 8275592
TI  - Iliopsoas bursitis in rheumatoid arthritis.
AB  - A 58-year-old woman with rheumatoid arthritis (RA) presented with persistent hip
      pain and an inguinal mass. Considerable liquid had collected inside the iliopsoas
      bursa, apparently not in communication with the hip joint, as shown by
      ultrasonography and computed tomography (CT). After one month of systemic
      steroidal therapy (25 mg/day prednisone), the palpable inguinal mass and pain had
      disappeared. Iliopsoas bursitis should be suspected in RA patients with a long
      history of disease presenting with an inguinal mass, persistent groin pain or
      unilateral leg swelling. The lack of communication between the hip joint cavity
      and bursa may be considered as a favourable prognostic index. Steroid treatment
      should be always attempted in order to avoid surgery.

PMID- 8275593
TI  - Acute myositis and dermatitis as the initial presentation of sarcoidosis.
AB  - We report a case of a patient who presented with symptoms of acute debilitating
      proximal muscle weakness, which mimicked acute polymyositis, accompanied by a
      hypopigmented papular rash. The histology of the skin and muscle demonstrated
      sarcoidosis. A review of the literature of acute sarcoid myositis and the various
      other myopathies of sarcoidosis is presented.

PMID- 8275594
TI  - Osteoporosis in rheumatoid arthritis.
AB  - Osteoporosis is recognised as a common complication of rheumatoid arthritis, with
      two characteristic patterns--juxta-articular and generalized bone loss.
      Increasingly sophisticated means of measuring bone turnover and identifying
      inflammatory mediators which affect bone resorption have enhanced our
      understanding of the disease process. The aetiology is multifactorial, involving
      disease-specific and general factors, but the relative importance of the various
      risks remains uncertain. The evidence for a protective role for oestrogens and
      the detrimental effect of low dose corticosteroids will be discussed. Biochemical
      assessment of bone loss lacks sensitivity and specificity, but the rapid
      improvement in radiological techniques for measuring bone mineral density have
      improved our ability to diagnose and assess disease progression. The diagnosis
      and treatment of specific risk factors, such as testosterone or vitamin D
      deficiency, may be helpful in a few patients, but the ultimate aim must be the
      early diagnosis and prevention of this potentially catastrophic complication.

PMID- 8275595
TI  - Prevalence of inflammatory rheumatic diseases in an adolescent urban student
      population, age 12 to 18, in Belgium.
AB  - In order to determine the prevalence of inflammatory rheumatic diseases in an
      urban secondary school student population, a questionnaire dealing with past or
      present joint, tendon, axial, gastrointestinal, ocular and dermatological
      symptoms was completed by 2,990 students of secondary schools in Antwerp and
      Ghent. The parents were asked to complete a questionnaire regarding the family
      medical history. From these 2,990 students, 524 were selected for further
      investigation by a rheumatology resident, who checked the answers to the first
      questionnaire and performed a clinical examination. Forty-one adolescents with a
      presumptive history or present symptoms of inflammatory rheumatic diseases were
      retained. These students were examined by the medial staff of the rheumatology
      department; if necessary, a complementary biochemical and radiological
      examination was performed. Five cases of definite juvenile chronic arthritis
      (JCA) (with polyarticular onset in 1 case and late pauciarticular onset in 4
      cases) and 4 cases of presumptive late pauciarticular onset JCA were detected,
      resulting in a prevalence of 167 per 100,000 for definite JCA and of 301 per
      100,000 for possible JCA. This prevalence rate is higher than that generally
      described. This method of investigation effectively allows the detection of
      milder and spontaneously remitting cases of JCA. It further enabled us to
      definite case and 4 presumptive cases of various previously undiagnosed forms of
      JCA.

PMID- 8275596
TI  - Measurement of functional status in juvenile chronic arthritis: evaluation of a
      Swedish version of the Childhood Health Assessment Questionnaire.
AB  - Few well-validated self-and/or parent-administered instruments are available for
      measuring functional status in children with rheumatic diseases. Parts of the
      Stanford Health Assessment Questionnaire (HAQ) have been adapted for use in
      children in the so-called Child HAQ. The aim of this study was to investigate the
      validity of this instrument in a Swedish setting. The Child HAQ was administered
      to 186 patients and 211 patients participating in a population-based follow-up
      study of juvenile chronic arthritis (JCA) in southwestern Sweden. The EULAR
      criteria were used for inclusion. Children who were 9 years of age or older self
      reported. Reliability, evaluated by test-retest, inter-observer correlations and
      internal reliability, was excellent. Convergent validity was demonstrated by
      strong correlations of the disability index, pain, and morning stiffness with
      disease activity and the Steinbrocker functional classes. Discriminant validity
      was evidenced by the capacity of the instrument to evaluate patients as being
      active or in remission. Thus, the Child HAQ showed excellent measurement
      performance in a Swedish setting when using parents or children more than 9 years
      old as responders.

PMID- 8275597
TI  - Lack of evidence for a defect in major histocompatibility complex class I
      expression in rheumatoid arthritis.

PMID- 8275598
TI  - Familial Mediterranean fever is not associated with the antiphospholipid
      syndrome.

PMID- 8275599
TI  - Brachial artery aneurysm and peripheral gangrene in a patient with Behcet
      disease.

PMID- 8275600
TI  - Anti-lactoferrin autoantibodies in rheumatoid arthritis.

PMID- 8275601
TI  - Pericardial disease in scleroderma: prognosis and clinical associations.

PMID- 8275602
TI  - Investigation of the anti-Ro autoantibody levels in patients with systemic lupus
      erythematosus.

PMID- 8275603
TI  - Morbidity and mortality patterns of ventilator-dependent children in a home care
      program.
AB  - We evaluated the effectiveness of the Home Care Program of Children's Hospital of
      Winnipeg for ventilator-dependent children by retrospectively examining morbidity
      and mortality from February 1, 1979, to July 31, 1992. For the 22 study subjects,
      the cause of chronic respiratory failure was neurologic disorders for 14 (64%)
      (group A) and pulmonary disorders for eight (36%) (group B). There were no
      significant differences between groups A and B in the average number of hospital
      days, readmission rate, or length of stay per admission. Eleven patients have
      remained ventilator-dependent at home, four no longer require mechanical
      ventilation, and seven died. Factors such as diagnosis, type of family, home
      location, age at initiation of mechanical ventilation, and initial duration of
      hospital stay did not influence morbidity or mortality in either group. Within
      the overall mortality rate of 32% is a higher rate among patients whose disorders
      initially carried a poor prognosis. Ventilator-dependent children can be
      successfully managed at home, with few nonelective hospital readmissions, through
      a well-organized home care program.

PMID- 8275604
TI  - Ethical and quality-of-life issues in ventilator-dependent children.

PMID- 8275605
TI  - Physicians' attitudes toward and knowledge of child care.
AB  - A questionnaire designed to elicit information about training in child-care
      issues, frequency of discussion during office visits, and attitudes regarding
      specific medical and developmental issues of child care was sent to randomly
      chosen board-certified family practitioners and pediatricians in District 3 of
      the American Academy of Pediatrics. Among respondents, 39% said they felt
      uncomfortable discussing child-care issues and 85% felt that their training in
      this area was inadequate. Forty-three percent reported rarely or never discussing
      child care during an initial visit. More formal training is needed to address
      issues of child care.

PMID- 8275606
TI  - Adolescent Sexuality: Part 2. Contraception.
AB  - The United States has the highest rate of teen pregnancy in the Western world.
      Although abstinence may be the ideal solution for the prevention of this problem,
      one half of adolescents in the United States are sexually active. This article
      reviews the epidemiology of contraception among adolescents, barriers to
      effective use of contraception, and ways to improve efficacy. Major methods of
      contraception, including oral contraceptive pills, Norplant, Depo-Provera,
      condoms, spermicide, sponge, intrauterine device (IUD), diaphragm, and
      rhythm/periodic abstinence, are discussed along with method-specific issues
      related to adolescents.

PMID- 8275607
TI  - Acute renal failure following amoxicillin overdose.

PMID- 8275608
TI  - Severe intracranial hemorrhage in a term neonate associated with maternal
      acetylsalicylic acid ingestion.

PMID- 8275609
TI  - Erythromycin. Still a good choice for strep throat.

PMID- 8275610
TI  - Cocaine poisoning: an easily missed diagnosis in an infant.

PMID- 8275612
TI  - Pilomatrixoma: patient report of a common childhood tumor.

PMID- 8275611
TI  - Endobronchial tuberculosis presenting as respiratory failure in an infant.

PMID- 8275613
TI  - Clostridium septicum sepsis and meningitis as a complication of the hemolytic
      uremic syndrome.

PMID- 8275614
TI  - Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics.
AB  - The bioavailability of some dihydropyridine calcium antagonists can be markedly
      augmented by grapefruit juice and may involve the bioflavonoid naringin. The
      pharmacokinetics of nisoldipine coat-core tablet were studied in a Latin square
      designed trial in which 12 healthy men were administered the drug with water,
      grapefruit juice, or encapsulated naringin powder at the same amount as that
      assayed in the juice. Compared with water, grapefruit juice increased the maximum
      concentration of nisoldipine to 406% +/- 73% (mean +/- SEM; range, 107% to 836%;
      p < 0.001), increased the area under the plasma concentration-time curve to 198%
      +/- 46% (range, 81% to 682%; p < 0.001), and reduced time to reach maximum
      nisoldipine concentration to 58% +/- 9% (range, 13% to 100%; p < 0.01), probably
      by inhibition of presystemic metabolism and possibly by enhancement of drug
      dissolution. The interaction could not be predicted from baseline
      pharmacokinetics with water and resulted in greater interindividual variability.
      The naringin capsule did not change nisoldipine pharmacokinetics. All treatments
      produced minor effects on supine blood pressure and heart rate, probably because
      subjects were normotensive. Current information supports the cautioning of
      patients about concomitant ingestion of grapefruit juice and nisoldipine.

PMID- 8275615
TI  - Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single-
      and multiple-dose administration to normal volunteers.
AB  - The pharmacokinetics and safety of the L-valyl ester pro-drug of acyclovir,
      valaciclovir (256U87), were investigated in two phase I, placebo-controlled
      trials in normal volunteers. These included a single-dose study with doses from
      100 to 1000 mg (single cohort) and a multiple-dose investigation with doses from
      250 to 2000 mg (five separate cohorts). In each cohort, eight subjects received
      valaciclovir and four subjects received placebo. Pharmacokinetic findings for
      valaciclovir and acyclovir were consistent in the two studies. Valaciclovir was
      rapidly and extensively converted to acyclovir, resulting in significantly
      greater acyclovir bioavailability (approximately threefold to fivefold) compared
      with that historically observed with high-dose (800 mg) oral acyclovir. At the
      higher valaciclovir doses, acyclovir maximum concentration and daily area under
      the concentration-time curve approximated those obtained with intravenous
      acyclovir. The favorable safety profile and enhanced acyclovir bioavailability
      from valaciclovir administration has prompted additional clinical evaluations for
      zoster and herpes simplex virus treatment, as well as cytomegalovirus suppression
      in immunocompromised patients.

PMID- 8275616
TI  - Decreased acetylation of isoniazid in chronic renal failure.
AB  - Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were
      compared with parameters obtained from 14 patients with chronic renal failure. In
      the 29 normal rapid acetylators and eight normal slow acetylators, the mean
      plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours,
      respectively. The plasma half-life values of isoniazid in patients with chronic
      renal failure varied widely from 1.30 to 10.13 hours, but the values were
      significantly longer than those of normal subjects. Because isoniazid clearance
      is governed mainly by hepatic metabolism, such a significant prolongation of
      plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of
      isoniazid were reevaluated in the same patients with chronic renal failure after
      the kidney transplantation. After successful kidney transplantation, the
      shortening of isoniazid half-life was pronounced and the nonrenal clearance was
      markedly increased. These findings indicate that decreased isoniazid clearance in
      chronic renal failure is caused in minor part by the decreased renal excretion of
      isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.

PMID- 8275617
TI  - Absence of correlations among three putative in vivo probes of human cytochrome
      P4503A activity in young healthy men.
AB  - In vitro studies with human liver microsomes have shown that erythromycin N
      demethylation, dapsone N-hydroxylation, and the 6 beta-hydroxylation of cortisol
      are all primarily mediated by P4503A4. Trait measurements to assess the in vivo
      level of activity of these separate oxidations have also been developed
      previously. This study investigated the relationships among the three phenotypic
      trait measurements in 30 young healthy white men. The frequency distributions of
      the trait values were all unimodal, with a twofold range for the erythromycin
      breath test and the urinary dapsone recovery ratio; the urinary 6 beta
      hydroxycortisol/cortisol ratio was more variable, with a 17-fold range of values.
      No statistically significant correlations were observed among any of the trait
      measurements (dapsone recovery ratio versus erythromycin breath test: r = -0.07,
      p = 0.7; urinary 6 beta-hydroxycortisol/cortisol ratio versus erythromycin breath
      test: r = -0.12, p = 0.6; urinary 6 beta-hydroxycortisol/cortisol ratio versus
      dapsone recovery ratio: r = 0.13, p = 0.5. This lack of any relationship was
      unexpected and the reason(s) is unknown; however, it is possible that factors
      such as route of administration and extrahepatic metabolism in the intestinal
      epithelium and kidney are involved. Further studies are required to identify and
      validate the use of an appropriate in vivo probe of P4503A4 in humans.

PMID- 8275618
TI  - Triazolam in cirrhosis: pharmacokinetics and pharmacodynamics.
AB  - Although it is frequently stated that patients with cirrhosis are more sensitive
      to benzodiazepines, the relative roles of impaired elimination and altered
      responsiveness have not been clarified. We evaluated the pharmacokinetics,
      pharmacodynamics, and sensitivity to triazolam in six patients with clinically
      stable cirrhosis and six age-matched control subjects. Our findings show that
      there were no significant differences between the patients with cirrhosis and the
      control subjects in any of the pharmacokinetic parameters. Drug effect, measured
      as postural sway, was also similar in the patients with cirrhosis and control
      subjects; therefore the ratio of effect area under the curve to concentration
      area under the curve, a measure of sensitivity, did not differ significantly
      between the patients with cirrhosis and the control subjects. Because triazolam
      is metabolized by P4503A, we hypothesized that the effects of cirrhosis on drug
      metabolism may differ with respect to the specific P450 responsible for the
      oxidation of this drug. These effects may differ because of the relative sparing
      of a specific P450 and because of an extrahepatic site of metabolism.

PMID- 8275619
TI  - Single-dose pharmacodynamics of diazepam and pentobarbital in substance abusers.
AB  - The likelihood that a given drug will be misused is related to its ability to
      alter mood, feeling, thinking, and perception in a manner that is liked by
      substance abusers. The subjective and behavioral effects of diazepam (10, 20, and
      40 mg), pentobarbital (120 and 240 mg as a positive control), and placebo
      (negative control), were evaluated in 12 subjects with histories of substance
      abuse by use of a double-blind, Latin square crossover study design. Drug
      administration was separated by a minimum of 3 days. Pharmacodynamic measures
      included subjective (euphoria, subject liking, sedation, and symptoms) and
      behavioral (signs and observed liking) responses. The time course and profile of
      subjective and behavioral responses were similar for diazepam and pentobarbital.
      Valid relative potency estimates for the pharmacodynamic measures indicated that
      diazepam is approximately 10 times as potent as pentobarbital. The study
      indicates that the reinforcing effects of diazepam are similar to pentobarbital
      in substance abusers.

PMID- 8275620
TI  - Beta-adrenergic responsiveness is regulated selectively in hypertension.
AB  - beta-Adrenergic receptor responsiveness is impaired in hypertension. A low-sodium
      diet both corrects this defect and lowers blood pressure. To determine whether
      upregulation of beta-adrenergic receptor function in hypertension might be
      related nonspecifically to lowering of blood pressure, vascular beta-adrenergic
      response was assessed after pharmacologic antihypertensive treatment by use of
      dorsal hand vein linear differential transformer techniques in patients with
      hypertension. Subjects were studied after randomized treatments with placebo and
      verapamil and after randomized treatments with verapamil and hydrochlorothiazide.
      After 2 weeks of treatment, verapamil lowered blood pressure in the subjects with
      hypertension but did not significantly upregulate vascular beta-adrenergic
      response (58% +/- 8% to 68% +/- 8%; p > 0.2 versus placebo). Further vascular
      beta-adrenergic responsiveness after treatment with hydrochlorothiazide did not
      significantly differ from that with verapamil (hydrochlorothiazide, 68% +/- 9%;
      verapamil, 53% +/- 7%; n = 8, p > 0.3). Thus, reduction of blood pressure with
      either verapamil or hydrochlorothiazide did not correct the defect in beta
      adrenergic responsiveness in hypertension. Vascular beta-adrenergic response
      appears to be regulated selectively in hypertension, not simply by lowering of
      blood pressure.

PMID- 8275621
TI  - Dose-ranging effects of candoxatril on elimination of exogenous atrial
      natriuretic peptide in chronic heart failure.
AB  - Seven patients with chronic heart failure were treated in single-blind crossover
      fashion with placebo and 10 mg, 50 mg, and 200 mg doses of the neutral
      endopeptidase inhibitor candoxatril to determine the effects of candoxatril on
      the elimination kinetics of exogenously infused atrial natriuretic peptide (ANP).
      An incremental dose-response effect was observed on the mean maximum observed
      plasma concentration (Cmax) of the active metabolite candoxatrilat (107.4, 453.5,
      and 1584 ng/ml in response to 10, 50, and 200 mg candoxatril, respectively).
      Pooled active versus placebo comparisons showed that candoxatril reduced the
      clearance (p = 0.021) and elimination rate constant (p = 0.006) and increased
      Cmax (p = 0.002) and time to reach Cmax (p = 0.01) of exogenous ANP.
      Individually, both 50 mg and 200 mg but not 10 mg candoxatril significantly
      altered the elimination kinetics of ANP. The most favorable effects were observed
      in response to 200 mg candoxatril, although even this dose may not have achieved
      the maximal modulating effect on elimination of circulating ANP.

PMID- 8275622
TI  - Smoking cessation, clonidine, and vulnerability to nicotine among dependent
      smokers.
AB  - OBJECTIVE: This study examines the efficacy of clonidine in smoking cessation and
      the influence of gender, history of major depression, and measures of nicotine
      dependence. METHODS: The study was designed as a 10-week double-blind randomized
      comparison stratified for gender and major depression. Three hundred subjects who
      smoked cigarettes heavily were enrolled in the study. Abstinence from smoking was
      evaluated by self-report and verified by serum cotinine levels. RESULTS: Gender,
      major depression recurrent type, and measures of nicotine addiction were risk
      factors for treatment failure. There was no clonidine effect in men, but there
      was a modest effect in women (odds ratio, 2.01; 95% confidence interval, 1.00 to
      4.10) that was most pronounced (odds ratio, 8.5; 95% confidence interval, 1.67 to
      43.62) among women with the highest risks. CONCLUSION: Measures of addiction and
      major depression predict treatment failure. Together they are stronger predictors
      of outcome than drug. Clonidine is a limited aid in cessation, and drug effects
      come primarily from women at high risk for treatment failure. An increased risk
      for psychiatric complications after smoking cessation was apparent among smokers
      with histories of major depression, particularly bipolar disease.

PMID- 8275623
TI  - Trial of oral physostigmine in amyotrophic lateral sclerosis.
AB  - We evaluated a double-blind, placebo-controlled, and double-crossover trial of
      oral physostigmine salicylate for a 9-month period in 13 of 25 patients with
      sporadic amyotrophic lateral sclerosis (ALS). A large dropout rate of 48% was
      secondary to eight deaths and four exclusions attributed to the incapability to
      swallow the tablets (physostigmine) and capsules (lecithin) or to attend the
      clinic. Parameters used for assessment of the drug efficacy included body weight,
      ALS score, Jamar grip strength, forced vital capacity, and maximum voluntary
      ventilation. It revealed slight benefit in reduced loss of grip strength compared
      with the pretrial and placebo periods. However, the rates of decline for body
      weight, ALS score, forced vital capacity, maximum voluntary ventilation, and
      megascore did not differ significantly between the pretrial, placebo, and
      physostigmine periods. We therefore concluded that overall no significant
      alteration in the clinical course was gained by oral physostigmine therapy in the
      13 patients with ALS who were included in this study.

PMID- 8275624
TI  - Ganciclovir in newborns.

PMID- 8275625
TI  - Introduction, clefts 1993. Past, present, and future.

PMID- 8275626
TI  - Facial clefting. Etiology and developmental pathogenesis.
AB  - This article has provided an overview of normal and abnormal facial morphogenesis
      and the factors that govern this process. Etiologic heterogeneity among patients
      encountered in treatment clinics has been emphasized. The implications of this
      information with respect to treatment, reproductive counseling, and prenatal
      diagnosis have been reviewed.

PMID- 8275627
TI  - Assessment of the patient with cleft lip and palate. A developmental approach.
AB  - Children with cleft lip and palate require interdisciplinary team care from
      infancy through adolescence. An understanding of developmental stages allows the
      cleft palate team to adapt and integrate its services into the rapidly changing
      life of the child. This article discusses the maturational, developmental stages
      of childhood and the services the child with cleft lip and palate and the child's
      family deserve through each stage. Health care providers in all settings may
      continue to provide appropriate care for all patients with cleft lip and palate,
      despite the challenges of a changing health care environment, by emphasizing the
      needs of the child in all developmental stages.

PMID- 8275628
TI  - Clefting and psychosocial adjustment. Influence of facial aesthetics.
AB  - This article briefly reviewed the research literature on the psychosocial
      correlates of facial clefts and described a program of research to study the
      relationship between severity of cleft impairment and psychosocial adjustment. In
      the past 40 years, there has been increasing recognition and research literature
      on the psychologic implications of facial clefts to patients and their families.
      Advances in both the knowledge base and the science of the psychologic correlates
      of facial clefts have been made. Children with clefts are not at greater risk for
      psychopathology than are individuals without clefts; however, they are at
      significant risk for social competence problems relating to development of
      friendships, progress in school, and participation in organizations. Problems
      with social competence have a negative effect on development. The ability of all
      children to make friends and to be liked by others is considered by most parents,
      teachers, and child development specialists to be a major developmental
      milestone. Not having friends and social withdrawal can cause parents or teachers
      to refer noncleft children to mental health professionals and is a predictor of
      impaired adult social competence and mental health. Studies of adults with clefts
      are consistent with studies of adults without clefts. Adults with repaired clefts
      are less likely to marry than are their noncleft siblings, and they have more
      problems with social withdrawal. Because facial attractiveness is well-known to
      affect peer acceptance, we hypothesized that the severity of the cleft deformity
      may have a significant impact on social competence. Consequently, we undertook a
      program of research to examine this question.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275629
TI  - Rotation-advancement repair of the unilateral cleft lip. One center's
      perspective.
AB  - Most surgeons agree that the Millard rotation-advancement is the procedure of
      choice for treatment of the incomplete cleft lip and milder complete cleft forms.
      It has been found to be an effective procedure for essentially all cleft cases,
      regardless of width, when the staged approach described is employed. To reach the
      goal of establishing near-perfect anatomy and function, a protocol, which
      capitalizes on the strengths of Millard's repair while minimizing its weaknesses,
      has been adopted. Three aspects of the protocol are emphasized in this article:
      (1) presurgical manipulation of the maxillary alveolar segments via passive
      molding appliances; (2) a staged approach to lip repair for wide complete clefts,
      which includes preliminary lip adhesion; and (3) adherence to a standardized
      technique, which will allow for a long-term clinical study.

PMID- 8275630
TI  - Unilateral cleft lip repair. Z-plasty.
AB  - All unilateral clefts of the lip are not alike. The deficiencies that exist,
      especially in the lateral lip element, can vary considerably. Because of these
      differences, it is unreasonable to expect one technique of repair to satisfy all
      situations. In more difficult complete unilateral cleft lip deformity, the Z
      plasty repairs described in this article better satisfy the goals of this
      surgery.

PMID- 8275631
TI  - Bilateral cleft lip. An unorthodox management.
AB  - Successful repair of bilateral cleft lip requires attention to the soft-tissue
      anomalies of the lip and nose and the hard-tissue defects of the maxilla. An
      algorithm for the management of the infant with bilateral cleft lip is presented.
      A multidisciplinary approach that uses lip adhesion and passive alveolar molding
      plates to set the stage for subsequent definitive lip and columellar
      reconstruction is discussed. This approach differs from most others because of
      reliance on the mucosal circulation of the prolabium.

PMID- 8275632
TI  - Issues and controversies in the management of cleft palate.
AB  - Cleft palate management is complex. There is no current agreement on the
      appropriate treatment strategy. Extensive disagreement on the pathophysiology,
      timing of intervention, and techniques of surgical repair have added to the
      confusion. To provide a comprehensive guide to the management of cleft palate is
      difficult. However, several main points should be emphasized. Normal speech
      should be the most important consideration in the therapeutic plan. Growth
      disturbance should be minimized, but not at the expense of speech impairment,
      because the facial distortion can be satisfactorily managed with further surgery,
      whereas speech impairment can often be irreversible. We believe repair of cleft
      palate to establish a competent velopharyngeal sphincter should be completed from
      6 to 12 months of age. This is done early enough to minimize the development of
      an often irreversible pathologic compensatory speech pattern, but late enough not
      to increase significantly the surgical risk to the infant. Surgical interventions
      should be designed to cause minimal disruption of the palate, to decrease the
      severity of subsequent growth problems. There is a need for well-controlled,
      prospective studies to establish the validity of the widely different claims of
      superior results from various techniques. We believe strongly that cleft patients
      should be managed in a center with a multidisciplinary team. The benefits of
      these teams have been elaborated. Cleft palate embodies one of the major tenets
      of plastic surgery, the achievement of an aesthetic result with minimal
      interference with function. Cleft palate remains a significant and interesting
      challenge for current and future plastic surgeons.

PMID- 8275633
TI  - Primary (early) alveolar bone grafting.
AB  - Early primary bone grafting is successful when performed as a separate operative
      procedure after lip repair and before palate closure. It must be done in
      conjunction with neonatal orthopedics. The graft is placed only after the
      alveolar segments have molded and grown to a butt joint. Minimal soft-tissue
      dissection of the alveolus and maxilla are performed. The graft stabilizes arch
      form, allows for tooth migration and eruption through its site, and decreases
      anterior and posterior crossbite. There is no facial growth attenuation, and a
      good foundation for further soft-tissue growth is provided.

PMID- 8275634
TI  - Secondary (intermediate) alveolar bone grafting.
AB  - Secondary bone grafting of the maxilla and the residual alveolar clefts at the
      stage of transitional dentition, and in conjunction with orthodontic treatment,
      has become a well-accepted treatment modality. This article discusses the goals
      of the procedure, the timing of the bone graft, and the design of the flap for
      soft-tissue coverage of the bone graft.

PMID- 8275635
TI  - Velopharyngeal insufficiency and secondary palatal management. A new look at an
      old problem.
AB  - The main objective of primary palatoplasty is to achieve adequate velopharyngeal
      (VP) function and normal oral-nasal resonance. Many children, however, who
      undergo cleft palate repair fail to develop normal VP function. Symptoms of
      velopharyngeal insufficiency (VPI), such as hypernasality and audible nasal air
      emission, may have a variety of causes, which underscores the need for
      comprehensive evaluation. This article focuses on the problem of VPI and
      emphasizes the need for differential diagnosis at the most critical step in
      management planning. The challenge of the future is to implement the team
      approach, integrating the expertise of speech scientists and plastic surgeons, so
      that differential diagnosis can and will lead to differential management.

PMID- 8275636
TI  - Maxillary orthopedics.
AB  - Although there may never be uniformity of opinion on the use of maxillary
      orthopedic appliances or definitive data supporting their universal use in
      treatment regimens, they are an integral part of cleft lip and palate care. Many
      appliances, both active and passive, are used by teams of highly skilled
      specialists to normalize the congenital alveolar defect. The major difficulty in
      reaching a consensus among care providers is due to maxillary orthopedics being
      but one interventional aspect of a sequence of events in the habilitation effort.
      Cleft care begins in infancy and extends throughout the developmental years. The
      period of assessment of treatment regimens and outcomes extends almost over a
      researcher's lifetime. By placing the cleft structures in a more favorable oral
      configuration in concert with the oral environment, the greatest growth potential
      can be achieved.

PMID- 8275637
TI  - Orthodontic management of the cleft lip and palate patient.
AB  - The importance of the dentition and contribution of the orthodontist to the care
      of cleft patients from infancy to adulthood are presented. Close communication
      between orthodontists and surgeons is emphasized. The orthodontic treatment plan
      is developed around the anatomic, functional, and developmental needs of the
      patient.

PMID- 8275638
TI  - Orthognathic surgery in the cleft lip and palate patient.
AB  - Orthognathic surgery for the cleft lip and palate patient should be designed to
      achieve good facial aesthetics and a stable, functional occlusion. Maxillary and
      mandibular osteotomies, which benefit cleft lip and palate patients with
      associated dentofacial deformities, should be modified to meet the needs of the
      individual patient. Soft-tissue correction of the upper lip and nose adds to the
      overall aesthetic result, but should be performed as a separate procedure.

PMID- 8275639
TI  - Cleft nose. Form and function.
AB  - Clefts of the lip and palate frequently produce nasal deformities that tend to
      reduce the size of the nasal airway. Surgical correction of nasal, palatal, and
      pharyngeal structures may compromise breathing further. A significant number of
      individuals with cleft noses mouthbreathe to some extent because of the high
      prevalence of airway compromise.

PMID- 8275640
TI  - Primary nasoplasty in unilateral and bilateral cleft nasal deformity.
AB  - A six-step nasoplasty for the primary correction of the unilateral and bilateral
      cleft nasal deformity is presented. A review of the evolution of primary nasal
      reconstruction and preliminary results of the method are described and
      illustrated.

PMID- 8275641
TI  - Correction of secondary cleft lip and nasal deformities.
AB  - Surgical techniques for the correction of commonly seen secondary cleft
      deformities of the lip and nose are reviewed. These techniques include revision
      of the vermilion, vermilion--cutaneous junction, philtrum, nasal base, and nasal
      tip. Timing of intervention and coordination with other orofacial therapies are
      emphasized.

PMID- 8275642
TI  - Craniofacial clefts.
AB  - No major breakthroughs have occurred since Kawamoto last discussed this topic in
      the Clinics in 1976. Advances such as early surgery, cranial bone grafting,
      modern methods of fixation, and tissue expansion have been applied with success
      to craniofacial clefts as in the treatment of other craniofacial deformities.
      Twenty years have passed since Tessier first presented his classification of
      craniofacial clefts, and that interval has served to reinforce the magnitude of
      Tessier's contribution to craniofacial surgery.

PMID- 8275643
TI  - Prospectives in cleft lip and palate repair.
AB  - A recent focus on fetal surgery has raised the possibility of fetal cleft lip and
      palate repairs. Because of the fetus's marked plasticity, fetal repairs may have
      results that more closely approximate normality. Furthermore, the impact on cost
      management could be dramatic with a decreased need for extensive postoperative
      care, orthodontia, and speech therapy. This article considers the future
      prospects of intrauterine cleft lip repair as the next generation of surgical
      advances.

PMID- 8275644
TI  - Levomethadyl acetate to be used in narcotic treatment programs.

PMID- 8275645
TI  - Three categories of nonprescription drug products to carry new warnings.

PMID- 8275646
TI  - Ketoconazole and gastric acidity.

PMID- 8275647
TI  - Prophylaxis with aztreonam plus metronidazole during appendectomy.

PMID- 8275648
TI  - Zolpidem: a nonbenzodiazepine hypnotic for treatment of insomnia.
AB  - The pharmacology, pharmacokinetics, and clinical efficacy of zolpidem tartrate, a
      new hypnotic agent, are described. Zolpidem belongs to the imidazopyridine class.
      It exhibits high-affinity binding at a benzodiazepine-receptor subtype that is
      located in the cerebellum and cerebral cortex but not in the spinal cord or
      peripheral tissues. It decreases sleep latency and increases total sleep time and
      sleep efficiency without affecting sleep architecture. Zolpidem tartrate is
      absorbed rapidly. Bioavailability is 67% after oral doses of 5-20 mg.
      Pharmacokinetics show age-related and sex-related variations. The disposition of
      zolpidem is reduced in hepatically and renally impaired patients. Clinical
      studies have shown effectiveness of zolpidem in increasing sleep time and
      decreasing sleep latency. It has demonstrated efficacy equal to that of
      benzodiazepines without causing rebound insomnia or withdrawal effects.
      Comparative trials have found zolpidem as effective as flunitrazepam, flurazepam,
      and triazolam. The optimum dose of zolpidem tartrate is 10 mg at bedtime; 5 mg
      for elderly patients. Adverse reactions to zolpidem are dose-related and have
      primarily CNS and gastro-intestinal manifestations. Zolpidem exhibits similar
      efficacy to the benzodiazepines in the treatment of insomnia. Zolpidem's
      advantages over benzodiazepines are that it does not lead to tolerance,
      withdrawal phenomena, or REM rebound; however, for short-term, as-needed use,
      these advantages are not relevant.

PMID- 8275649
TI  - Comparative efficacy of glycerin enemas and suppository chips in neonates.

PMID- 8275650
TI  - Bezoar formed by fragments of extended-release nifedipine tablets.

PMID- 8275651
TI  - Criteria for use of aldesleukin in adults.

PMID- 8275652
TI  - [Man, changing society and medicine of the future].

PMID- 8275653
TI  - [Radiographic examination of the pelvis in patients under periodic hemodialysis
      for terminal uremia].
AB  - Significant signs of uremic osteodystrophy were found at Rx examination of the
      pelvis in 29 out of 72 uremic patients (40%) undergoing maintenance hemodialysis.
      It is therefore thought that Rx of the pelvis, although it is more significant
      for some signs (brown tumors, alterations of the trabecular structure,
      enlargement of Ward's triangle) than for others, such as subperiosteal
      resorption, should not be neglected in these patients.

PMID- 8275655
TI  - [Physiological and psychopathological aspects of eating behavior].
AB  - Eating behaviour variations are often observed in medical practice. Sometimes
      they are physiological manifestations, rarely they are paraphysiological, many
      times they amount to pathological behaviour. Their heterogeneity could account
      for treatment problems met by the family doctor. Our study was aimed to increase
      the family doctor's attention to the eating behaviour of their patients. Greater
      awareness in family doctors of problems in their patients' eating behaviour may
      be apt to lead to an improvement in dietary habits and consequently to greater
      psychologic and physical wellbeing of the patients.

PMID- 8275654
TI  - [Clinical evaluation of DHEA-S plasma levels and possible therapeutic value of
      the hormone in the third trimester].
AB  - Three groups of women were studied. The first included women without obstetric or
      systemic pathology; in these, plasma concentrations of progesterone, E, and DHEA
      S were assayed at 30-40 weeks of pregnancy. The second group comprised women
      after physiological first delivery at term, and in these the plasma levels of the
      same hormones were assessed. In the third group, comprising women at 38 weeks of
      pregnancy with unripened cervix and DHEA-S plasma levels that were by 1-2 weeks
      below those of women with ripened cervix of the same gestational age, the effect
      of repeated perfusion with DHEA-S was examined.

PMID- 8275656
TI  - [Short-term antibiotic prophylaxis in surgery].
AB  - This clinical study was carried out in our division on 106 patients undergoing
      surgery for various pathologies in the period from May to September 1991; the aim
      of this study was the evaluation of short-term antibiotic prophylaxis before and
      after surgery: either imipenem-cilastatin, or cephalosporin or no treatment.
      Imipenem-cilastatin was found to be the antibiotic of choice for short-term
      prophylaxis.

PMID- 8275657
TI  - [The importance of follow-up of colorectal polyps].
AB  - In this paper, we have considered the indications for coloscopy for the screening
      of colon polyposis. On the basis of its sensitivity in detection and follow-up of
      colo-rectal cancer, we tried to determine the exact procedure to be followed
      subsequent to the discovery and ablation of a polyp. We have outlined the
      following parameters to be observed during the period of follow-up: dimension,
      number, histologic features of the polyp, age, general conditions and familiarity
      of the patient for colorectal cancer.

PMID- 8275658
TI  - [Effects of thermal balneo-fangotherapy on extra-articular rheumatic diseases in
      relation to sports activity].
AB  - Therapeutic muds have been applied-at "Terme dei Papi", Viterbo-to 30 subjects
      with subchronic extra-articular rheumatism (S.I.R., Italy 1986). Favourable
      effects have been obtained in a great majority of subjects treated. Improvement
      was obtained concerning provoked pain, spontaneous pain as well as function of
      sprained joints.

PMID- 8275659
TI  - [Tauro-ursodeoxycholic acid vs. ursodeoxycholic acid in the dissolution of
      biliary calculi. Results of a single blind study].
AB  - Out of 34 patients enrolled and randomized, 31 completed the 6 months study
      period. Fifteen were treated with TUDCA, and 16 with UDCA. Dosage for both drugs
      was 10 mg/kg body weight daily. Superiprisingly, TUDCA was not found to be more
      active than UDCA in dissolving, totally or partially, the gallbladder stones;
      indeed, total dissolution was more frequent in the UDCA group. Since the two
      groups were similar as to number and size of the stones, the better results with
      UDCA cannot be attributed to the characteristics of the calculosis but must be
      ascribed to the molecule used. Both drugs induced an improvement in dyspeptic
      symptoms, but from this point of view, too, UCDA was more effective than TUDCA (p
      < 0.01). Finally, tolerability was also significantly better for UDCA, although
      TUDCA was altogether acceptable.

PMID- 8275660
TI  - [Role of magnetic resonance in the evaluation of testicular diseases].
AB  - The above paper was intended to evaluate the usefulness of MRI in the study of
      pathologies involving the testis, on the basis of the authors' experience and of
      the relevant literature. Pathologies considered included cryptorchidism, torsion
      of the spermatic cord, epididymitis, orchitis, and testicular tumors. MRI proved
      very useful in cryptorchidism, thanks to the multiple planes and good contrast
      resolution between different tissues. It also yields valuable information
      allowing to distinguish between malignant transformation of the retained testicle
      and its fibrotic involution. In malignant pathologies, MRI is useful for
      differential diagnosis between seminomatous and non-seminomatous tissues, while
      for purposes of staging its accuracy is only 36% but is nevertheless superior to
      that of U.S. (45%). In the case of other pathologies, MRI findings are non
      specific, and the technique should therefore be employed only when U.S. findings
      are unsatisfactory.

PMID- 8275661
TI  - [A case of fulminating hepatitis C].
AB  - The case is described of a young drug addict suffering from acute viral hepatitis
      type C evolving towards coma and fatal outcome. The clinical features were those
      typical of fulminant hepatitis which so far have been considered infrequent in
      infections due to HCV.

PMID- 8275662
TI  - [To hear better is to feel better].

PMID- 8275663
TI  - Is cancer another "disease of adaptation"? Some insights into the role of stress
      and civilization.

PMID- 8275664
TI  - Molecular biology of viral hepatitis and hepatocellular carcinoma.
AB  - Five viruses are the major causes of hepatitis. These viruses are totally
      unrelated to each other in structure and mode of replication despite the
      similarity in the acute syndrome produced by each virus. HAV is a single-stranded
      RNA virus that has a very stable capsid and whose proteins are derived from a
      single polyprotein. HBV is a DNA virus that replicates through an RNA
      intermediate. HCV is a labile single-stranded RNA virus whose proteins are
      derived from a polyprotein. HDV is a defective RNA virus related to viroids that
      encodes a capsid antigen, delta antigen, and requires the envelope protein of HBV
      (HBsAg) for its propagation. HEV is a labile RNA virus that is unrelated to other
      known viruses. Hepatitis B, C, and D can cause chronic hepatitis. Both chronic
      hepatitis B and C virus infections are associated with primary hepatocellular
      carcinoma. The most likely mechanism for hepatitis B and C promotion of primary
      hepatocellular carcinoma in that these viruses cause chronic inflammation and
      increased mitotic activity of the pluripotent oval cells of the liver. Most
      likely, primary hepatocellular carcinoma arises out of synergy between chronic
      viral infection and some other carcinogenic stimulus such as exposure to a
      hepatotoxin.

PMID- 8275665
TI  - Management of thyroid cancer.

PMID- 8275666
TI  - The role of the primary physician in detecting cancer.

PMID- 8275667
TI  - Diagnosis and treatment of sarcoidosis.

PMID- 8275668
TI  - Evaluation of thyroid nodules.

PMID- 8275669
TI  - Cutaneous malignant melanoma--the party line and more--with a word on "safe sun".
AB  - Although the incidence of melanoma in adults seems to be increasing in recent
      decades, the survival rate has improved too, largely because of early diagnosis.
      Early diagnosis results in definition of a low risk primary group, for which
      conservative therapy is warranted. High risk primary patients still face
      controversial decisions regarding more radical surgery, a topic for another
      opinion paper. Patients with recurrences where fresh tissue can be made available
      should be considered for autologous tumor vaccine.

PMID- 8275670
TI  - Functioning tumors of the adrenal gland.

PMID- 8275671
TI  - Surgical treatment of solitary and multiple metastatic tumors to the lung.

PMID- 8275672
TI  - An evaluation of the safety of low energy emission therapy.

PMID- 8275673
TI  - Re-inventing progressive community psychiatry: the use of history.
AB  - Over the last half-century progressives in community psychiatry have challenged
      the social order while addressing the needs of persons with psychiatric
      disorders. Recently, however, their vision and energy has faltered. A re
      evaluation of the progressive position is essential, beginning with a review of
      its historical experience. Unfortunately, modern psychiatry has become
      increasingly ahistorical. Those histories that do exist reveal little about the
      experiences of progressive practice and tend to attack it from the right or from
      the left. There is a tremendous need to synthesize new socially-oriented
      histories of the progressive movement in community psychiatry.

PMID- 8275674
TI  - The biomedicalization of psychiatry: a critical overview.
AB  - The biomedical model currently dominates psychiatric clinical practice and
      research. Unfortunately, this dominance had led increasingly to biological
      reductionism. This paper examines the historical and sociopolitical underpinnings
      of the biomedical model, and illustrates some of the common scientific
      distortions of reductionistic thinking. These observations are applied to recent
      directions in mental health policy and are used to provide a basis for
      alternative perspectives of mental illness and psychiatric research.

PMID- 8275675
TI  - Psychotherapy, neutrality, and the role of activism.
AB  - Was the sixties activist merely acting out unresolved Oedipal conflicts? Is the
      analyst who interprets the activist's neurotic conflicts actually "neutral"?
      Issues from the sixties debate are relevant to today's discussion of activism in
      public mental health. For instance, why, at a time of shrinking public service
      budgets and unprecedented suffering on the part of mental patients, have the
      providers and consumers of public mental health services not become more active
      in struggles to reorder our unfortunate social priorities? The discussion
      proceeds to an exploration of the therapeutic effect of activism.

PMID- 8275676
TI  - Community empowerment: the alternative resources movement in Quebec.
AB  - In order to achieve true community participation in mental health care, a
      redistribution of decision-making power is needed. Currently, this power is
      almost exclusively in the hands of psychiatric institutions and the state.
      Community participation would require greater representation from community
      organizations. This paper describes the history of the alternative resources
      movement in Quebec. This movement has challenged the health care system and
      promoted innovative therapeutic approaches. In this process, community
      organizations have been faced with the difficult task of gaining more power while
      maintaining strong links with the communities they serve.

PMID- 8275677
TI  - Rethinking work with "multicultural populations".
AB  - This article examines the importance of ethnic and cultural factors in mental
      health and mental illness, through consideration of race and culture in the
      diagnosis and treatment of mental illness, by examining patterns of service
      utilization by multicultural populations, and by advocating for policies which
      support multicultural initiatives in public mental health.

PMID- 8275678
TI  - Progressive psychiatry: a research agenda.
AB  - It is possible to create a new research agenda based on an alternative
      perspective of human behavior and mind. After describing the theoretical tenets
      of this alternative perspective, illustrations of a new research agenda are
      presented. Such a research agenda would: (1) create new points of departure; (2)
      examine social relations underlying all variables; (3) more fully explore
      "unexplained variance;" (4) focus on the adaptive interaction of individuals
      within their world. Such research aims towards enhancing human uniqueness,
      action, and spirit.

PMID- 8275679
TI  - Methods in heart rate variability analysis: which tachogram should we choose?
AB  - We investigated the practical impact of the representation of the cardiac rhythm-
      the cardiotachogram--on two elementary spectral indexes in heart rate variability
      analysis: the low-frequency (0.07-0.14 Hz) and high-frequency (0.14-0.40 Hz)
      powers. Five commonly used tachograms (inter-beat interval function/series,
      counts, instantaneous heart rate function/series) were compared. Measurements
      were done on seven volunteers in the supine and standing positions. Ratios, and
      their deviations from 100%, of alternative power values were calculated. Mean low
      frequency and high-frequency ratio deviations ranged from 0 to 5% and from 6 to
      37%. The spectrum of counts yielded on average more (15-37%) high-frequency
      power. Spectra were incomparable without normalization of the tachogram with
      respect to heart rate. In conclusion, (i) the choice of a particular spectrum may
      lead to differing conclusions on the vagal contribution to heart rate variability
      and (ii) inconclusive results from studies using different tachogram variants can
      partly be due to the omission of normalization.

PMID- 8275680
TI  - A method for measuring and reporting manual data extraction reliability.
AB  - As health care costs have risen dramatically, the use of clinical data to analyze
      the quality of health care provided has increased. Central to this analysis is
      the means by which the clinical data itself is obtained. The reliability and
      validity of the data must be established in order to insure credible use of the
      data. The Wisconsin Ambulatory Review Project (WARP) is a three-year study of the
      nature of care in the ambulatory setting based on clinical data extracted
      retrospectively from written medical charts. This paper focuses on the method
      used to measure and report the reliability of the extraction process in the WARP
      study. The implementation of this methodology as a custom C program is described
      in detail.

PMID- 8275681
TI  - A model of human microvascular exchange: parameter estimation based on normals
      and nephrotics.
AB  - A mathematical model is formulated and used to describe the distribution and
      transport of fluid and albumin in the human circulation, interstitium and
      lymphatics. Two transcapillary mass exchange mechanisms are investigated: a
      homoporous 'coupled Starling model', in which transcapillary albumin diffusion
      and convection occur within the same pathway, and a heteroporous 'plasma leak
      model', in which variations in structure and pressure are permitted along the
      length of the capillary. Parameters used in the transport models are determined
      based on statistical fitting of simulation predictions to experimental data from
      normal humans and nephrotic patients. The data consists of interstitial fluid
      volumes and interstitial colloid osmotic pressures as functions of plasma colloid
      osmotic pressure. Model validation is carried out based on comparison of (i)
      simulation predictions with experimental data used in parameter estimation, (ii)
      estimated transport parameters with experimentally determined values, and (iii)
      simulation predictions with a set of dynamic data from an albumin infusion study.
      While both models with their best-fit parameter estimates provide a good
      representation of experimental data, the drawbacks of the plasma leak model are
      three-fold: it requires more estimated parameters than the coupled Starling
      model, little experimental information exists with which to compare these
      parameters and, with the best fit values obtained, the plasma leak mechanism
      becomes insignificant. The model that employs a Starling-type exchange mechanism
      will therefore be favoured in future applications.

PMID- 8275682
TI  - A PC-based on-line system for physiological in vivo and in vitro experiments.
AB  - A PC-based system for data acquisition, control of experiments and analysis of
      physiological signals has been developed. The system has a flexibility that makes
      it useful for many different types of study, e.g. hemodynamics, electrophysiology
      and in vitro studies of organ contractile functions. The experimental set-up is
      specified in a number of tables, which can be modified with a table editor. The
      specifications can be stored in file and used for other experiments with an
      identical experimental set-up. The recording of data can be done either
      intermittently or continuously, and the intermittent recordings are initiated
      automatically at predefined times, or manually. With a tape recorder utility,
      data can be recorded during an experiment and analyzed at a later time. The
      signal analysis module has a high degree of flexibility, achieved by parameters
      defining preprocessing, heartbeat detection, heartbeat selection and analysis.
      Data is presented on the display in three types of window, showing phasic
      signals, derived parameters in trend graphs and derived parameters in numerical
      form. Data is saved on disk in two types of file: sampled raw data or derived
      parameters (ASCII file). An Ethernet-based network is used to send data to a VAX
      cluster, where it is further processed in RS/1 or the BIOLAB analysis program.
      The source code has been written in Ada, and the compiler generated a 32-bit
      code, which facilitated the development of a large program with large data
      buffers.

PMID- 8275683
TI  - The estimation of population pharmacokinetic parameters using an EM algorithm.
AB  - An EM algorithm was used to analyse data arising from non-linear mixed-effects
      models. The fixed parameters were determined by maximum likelihood using simplex
      minimization, and the random effects were estimated using the EM algorithm after
      linearization with respect to the random effects. Applications to a simple linear
      model and population pharmacokinetics are described. The use of posterior
      parameter estimates to investigate covariate relationships is briefly described.
      The implementation of the estimation-maximization (EM) algorithm described here
      has proved in practice to be robust but slow. We intend to use a Newton-Raphson
      minimization routine in place of the simplex method to hasten convergence. The
      alternative linearization of the non-linear mixed effects model suggested by
      Lindstrom and Bates (Biometrics 46 (1990) 673-687) is much more unstable than the
      usual linearization, especially during the initial iterations. In the case of
      indomethacin the two linearizations produced very similar results. The individual
      posterior parameter estimates provided by the program are very useful for the
      detection of covariate relationships in population pharmacokinetic studies. In
      addition, the posterior means can be used in the estimation of pharmacokinetic
      pharmacodynamic relationships from sparse pharmacokinetic data where individual
      modelling is impossible.

PMID- 8275684
TI  - Acute tumor lysis syndrome complicating fludarabine treatment of prolymphocytic
      leukemia.
AB  - Tumor lysis syndrome rarely occurs during chemotherapy treatment of indolent
      lymphoid tumors. This report describes for the first time a case of acute tumor
      lysis syndrome complicating fludarabine treatment of prolymphocytic leukemia. In
      this particular case the patient had an unexpectedly rapid response to
      fludarabine 15 days after initiation of the first chemotherapy cycle, which was
      subsequently complicated by the development of tumor lysis syndrome. Until more
      data are known concerning fludarabine treatment of prolymphocytic leukemia,
      cautious monitoring of patients treated with fludarabine should be undertaken,
      even after completion of the chemotherapy course.

PMID- 8275685
TI  - Prevalence of maternal drug use near time of delivery.
AB  - Prenatal substance abuse is a problem of growing concern because of the negative
      effects it has on the health of the woman and developing fetus. To evaluate the
      prevalence of this problem in our community, anonymous toxicology studies were
      performed on 1,003 maternal urines. Samples were connected at time of delivery
      and selection bias was addressed. Results indicated that cocaine or marijuana
      metabolites were present in 4% of all urines. Among clinic patients, 12.4% tested
      positive (7.3% cocaine; 5.1% marijuana) and 1.3% tested positive among private
      patients (0.7% cocaine; 0.7% marijuana). Poor prenatal care was positively
      associated with substance use regardless of clinic or private care: 50% of those
      with fewer than three prenatal visits tested positive for cocaine or marijuana
      compared with 2% of those with more than three prenatal visits. Maternal age < 18
      years did not predict substance use. Program planning in Connecticut should
      progress with these data in mind.

PMID- 8275686
TI  - Public awareness of Lyme disease in obstetric, pediatric, and student settings in
      northwestern Connecticut.
AB  - The purpose of this study has been to survey the attitudes and understandings of
      Lyme disease by pregnant women, mothers, and ninth-grade students in Northwestern
      Connecticut. A sample of 100 obstetrical patients from two private obstetric
      offices, 100 mothers from four private pediatric offices, and 200 students from
      four secondary schools was asked to complete a 15 question survey about Lyme
      disease. In all groups, the responses indicated some misconceptions or a lack of
      knowledge about the manifestations, diagnosis, and treatment of Lyme disease, as
      well as about the transmission of Borrelia burgdorferi. This information
      indicates that better public education about Lyme disease is important.

PMID- 8275687
TI  - Cutaneous metastasis of colon carcinoma: a case report.

PMID- 8275688
TI  - Comments of Connecticut State Medical Society concerning proposed practitioner
      fee schedule regulations before the Workers' Compensation Commission 23 September
      1993.
AB  - The Connecticut General Assembly passed legislation last session reforming the
      workers' compensation system. One provision of that legislation mandated the
      establishment of a medical fee schedule for the workers' compensation system by 1
      October 1993. In response to that mandate, Workers' Compensation Commission
      Chairman Jesse Frankl relied upon the work and advice of his Medical Fee Advisory
      Group, of which the Connecticut State Medical Society was a member, and published
      proposed regulations for a medical fee schedule in the 31 August 1993 Connecticut
      Law Journal. A public hearing on those regulations was held on 23 September 1993.
      The following is testimony submitted by the Connecticut State Medical Society at
      that public hearing in support of those regulations.

PMID- 8275689
TI  - The name of the game is outcome research.

PMID- 8275690
TI  - Health reform: first moves on the board.

PMID- 8275691
TI  - In response to Dr. Arthur Koffler's article.

PMID- 8275692
TI  - In response to Dr. King's article.

PMID- 8275693
TI  - Clinical pharmacology of RU 486--an antiprogestin and antiglucocorticoid.

PMID- 8275695
TI  - The effect of nifedipine, a calcium channel blocker, on human spermatozoal
      functions.
AB  - In vitro addition of 0.1-100 microns of a calcium channel blocker, Nifedipine,
      resulted in a significant non-competitive inhibition in the uptake of Ca++. The
      activity of Ca(++)-dependent ATPase enzyme was also decreased. Motility of the
      spermatozoa was significantly arrested following incubation with different doses
      of the drug at 37 degrees C for different durations. The pattern of motility
      changed within two hours from rapid and linear progression to slow or sluggish
      linear or non-linear movement and finally to non-progressive motility or even
      immotility. Scanning electron microscopic studies revealed disruptive changes in
      the head as well as tail region and coiling of spermatozoa after Nifedipine
      treatment. An increase in the formation and release of malonyldialdehyde was
      observed following Nifedipine addition in a dose-dependent fashion. The membrane
      cholesterol and phospholipid contents were considerably lowered in the treated
      samples. The potential of such calcium channel blocking agent in the designing of
      male contraceptive programme is discussed.

PMID- 8275694
TI  - Bone metabolism in young women taking a monophasic pill containing 20 mcg
      ethinylestradiol: a prospective study.
AB  - The present one-year prospective study was performed to evaluate the effects of
      an oral contraceptive containing 20 mcg ethinylestradiol plus 0.150 mg
      desogestrel on bone metabolism in young women. Nineteen women aged 20 to 30 years
      completed the trial. Bone density was measured in the distal radius by dual
      photon absorptiometry before starting pill use and at the 3rd, 6th and 12th
      cycle. At the same time intervals, urinary hydroxyproline-to-creatinine ratio and
      serum alkaline phosphatase were evaluated. Bone density showed a slight, but not
      significant, increase at the end of the trial. Both urinary hydroxyproline-to
      creatinine ratio and serum alkaline phosphatase showed a significant decrease.
      The results suggest that bone resorption is reduced, although bone density in the
      distal radius is not significantly increased in young women using an oral
      contraceptive containing only 20 mcg ethinylestradiol for one year.

PMID- 8275696
TI  - The long-term effects of copper surface area on menstrual blood loss and iron
      status in women fitted with an IUD.
AB  - The long-term effects of copper surface area on menstrual blood loss (MBL) and
      iron status (hemoglobin, hematocrit, red cell count and indices, and serum
      ferritin) were evaluated in 25 healthy women who were observed for a period of 3
      years following insertion of an intrauterine device. MBL was determined
      objectively by the alkaline hematin method. The women (mean age 37.2 +/- 1.6 yr,
      range 27-46 yr) were fitted with a Multiload intrauterine device (IUD) with a
      copper surface area of either 250 mm2 (MLCu-250, n = 13) or 375 mm2 (MLCu-375, n
      = 12). MBL prior to IUD insertion was 55 +/- 8 ml for women subsequently fitted
      with a MLCu-250 and 59 +/- 9 ml for women fitted with a MLCu-375. An increase in
      MBL was recorded at all measurement points following IUD insertion (MLCu-250/MLCu
      375: 3 months: 55/49%; 6 months: 58/49%; 12 months: 64/41%; 24 months: 55/49%; 36
      months: 47/39%, NS). There were no significant differences in iron status
      parameters before IUD insertion between groups nor were there any significant
      changes recorded in any of these parameters after IUD insertion. Our findings
      that the increase in copper surface area from 250 mm2 to 375 mm2 had no effect on
      MBL were thus substantiated by the hematological findings. Based on the results
      of the present study, women from developed countries apparently tolerate an
      increased MBL of approximately 45% without developing anemia. Iron stores were
      unchanged indicating an adequate adaptive increase in intestinal iron absorption.

PMID- 8275697
TI  - Effect of the intrauterine contraceptive device on protein components of human
      uterine fluid.
AB  - The albumin, immunoglobulin G (IgG), immunoglobulin A (IgA), lysozyme,
      lactoferrin, alpha 1-antitrypsin, alpha 1x-antichymotrypsin, and neutral
      proteinase levels of uterine fluid and serum of IUD-bearing women were studied in
      relationship to the phase of the menstrual cycle, the length of IUD implantation
      and the presence of reported side effects. Selection of these proteins was based
      on their potential importance in IUD-induced contraceptive action and/or side
      effects. Generally, only small differences were found in the serum levels of
      these proteins during the cycle, with different length of implantation or between
      patients with and without side effects. However, transudation of proteins
      (albumin, IgG, alpha 1-antitrypsin, alpha 1x-antichymotrypsin) from blood into
      the uterine cavity was enhanced by the IUD, especially during the postmenstrual
      and premenstrual periods. The IUD enhanced the local secretory response even
      more, i.e., the increased release of proteins from the endometrium (lysozyme,
      neutral proteinase, IgA) and from leukocytes (lysozyme, lactoferrin). Protein
      changes occurred as the period of insertion increased. These changes in the
      uterine milieu may account in part for the contraceptive action of the IUD. The
      secretory proteins rather than the transudation products differed between
      patients who showed IUD-associated side effects vs. those who did not, implying
      that IUD-related pathology is primarily associated with changes in local
      secretory response. The possible role of each protein in the mechanism of IUD
      action is presented in view of the present findings.

PMID- 8275698
TI  - Effect of potassium deficiency and gossypol on urinary N-acetyl-beta
      glucosaminidase excretion in the rat.
AB  - Some men receiving gossypol in China developed elevated urinary N-acetyl-beta
      glucosaminidase (NAG) levels and hypokalemia. Since idiopathic hypokalemia occurs
      in China, hypokalemic nephropathy may have caused the elevated NAG levels. To
      learn if gossypol is directly nephrotoxic, we treated rats with a normal or low
      potassium diet with or without gossypol. The low potassium diet produced high NAG
      levels rather than the gossypol. This indicates the importance of differentiating
      hypokalemic nephropathy from drug nephrotoxicity in regions where idiopathic
      hypokalemia occurs.

PMID- 8275699
TI  - New developments: pediatric surgery.

PMID- 8275700
TI  - The RAP1GA1 locus for human Rap1-GTPase activating protein 1 maps to chromosome
      1p36.1-->p35.
AB  - Using a panel of somatic cell hybrids we have mapped the locus for Rap1-GTPase
      activating protein 1 (RAP1GA1) to human chromosome 1. Fluorescence in situ
      hybridization experiments independently confirmed the chromosomal localization
      and refined it to 1p36.1-->p35.

PMID- 8275701
TI  - Report of the first international workshop on human chromosome 14 mapping 1993.

PMID- 8275702
TI  - Nonrandom inactivation of the Y-bearing X chromosome in a 46,XX individual:
      evidence for the etiology of 46,XX true hermaphroditism.
AB  - We previously reported a subject with 46,XX true hermaphroditism who had a
      46,X,del(X) karyotype and Y-chromosomal sequences in genomic DNA. We hypothesized
      that the Y-chromosomal sequences were translocated to the deleted X chromosome
      and that the incomplete testis determination of this individual was the result of
      inactivation of the translocated X chromosome. In situ hybridization studies
      demonstrated that the Y-chromosomal sequences were located on the distal portion
      of the short arm of the deleted X chromosome. Investigation of the replication of
      the X chromosome, using a modified R-banding technique and localization of Y
      chromosomal sequences by in situ hybridization, showed that the translocated X
      chromosome was late replicating in all 100 EBV-transformed lymphoblasts that were
      examined. By contrast, when cells from a subject with 46,XX maleness were
      studied, the translocated X chromosome was late replicating in only 21 of 47
      cells. As the late-replicating X chromosome is presumed to be the inactive X
      chromosome, selection of cells in which the Y-bearing X chromosome has been
      inactivated may play a role in the incomplete testis determination in subjects
      with "Y-positive" 46,XX true hermaphroditism.

PMID- 8275703
TI  - Molecular cloning of an equine satellite-type DNA sequence and its chromosomal
      localization.
AB  - We have molecularly cloned portions of equine satellite-type DNA and investigated
      the organization of the DNA sequence of the cloned segments. Sequence analysis
      and dot-blot analysis, using the cloned sequence (ES200) as a probe, indicate
      that the satellite-type DNA sequence consists mainly of 221-bp tandem repeats and
      represents 3.7-11% of the equine genome. Southern blot analysis further shows
      that (1) no sequences homologous to ES200 exist in the human, swine, and bovine
      genomes and that (2) the fragment pattern of the satellite-type DNA produced by
      ApaI cleavage shows a slight difference among equine DNA samples, indicating a
      slight sequence variation between individual horses. To localize the satellite
      type DNA in the horse genome, chromosome spreads on glass slides were first
      subjected to G-banding to identify each chromosome and then hybridized in situ
      with biotin-labeled ES200. The chromosome banding, together with the
      hybridization, demonstrates that the satellite sequences are preferentially
      localized on the centromeric regions of all chromosomes except chromosomes 2, 9,
      and 11.

PMID- 8275704
TI  - Spontaneous sister chromatid differentiation (SCD) and sister chromatid exchange
      (SCE) in mouse blastocyst chromosomes.
AB  - The phenomenon of spontaneous differentiation (without bromodeoxyuridine in the
      culture medium) of sister chromatids of mouse chromosomes at the blastocyst stage
      of embryogenesis is described. The frequency of sister chromatid exchanges in
      such differentiated chromosomes was calculated.

PMID- 8275705
TI  - Regional localization of loci on chromosome 14 using somatic cell hybrids.
AB  - We have used a panel of human x rodent somatic cell hybrids containing
      translocations involving chromosome 14 to regionally localize 17 genes and 5
      random segments previously mapped to chromosome 14. Each hybrid cell line
      contains a specific fragment of chromosome 14, with breakpoints at 14q11.2,
      14q21, 14q22, 14q24.3 or in two different regions of 14q32.1. The enzyme
      deficient in glycogen storage disease type VI, liver glycogen phosphorylase
      (PYGL), has been localized by in situ hybridization to 14q21-->q22, near the q21-
      >q22 band interface. Four additional genes, chromogranin A (CHGA), myosin (MYH7),
      tRNA proline 2 (TRP2) and c-FOS (FOS) and four random segments, D14S26, D14S12,
      D14S14 and D14S13 have been more precisely localized. This study also defines a
      hybrid cell panel with seven mapping intervals, that will be useful for further
      physical mapping of new loci.

PMID- 8275706
TI  - Localization of the human alpha-fodrin gene (SPTAN1) to 9q33-->q34 by
      fluorescence in situ hybridization.
AB  - Using fluorescence in situ hybridization, the human alpha-fodrin gene
      (nonerythroid alpha spectrin, SPTAN1), a member of the spectrin gene superfamily,
      was mapped to 9q33-->q34. This locus is near the translocation breakpoint region
      in the Philadelphia (Ph1) chromosome, t(9;22)(q34;q11). In a human chronic
      myelogenous leukemia cell line with the Ph1 chromosome, K562, the alpha-fodrin
      gene mapped centromeric to the translocation breakpoint, indicating that the
      alpha-fodrin gene is not translocated to the Ph1 chromosome in this cell line.

PMID- 8275707
TI  - Multicolour fluorescence in situ hybridisation to order small, single-copy probes
      on metaphase chromosomes.
AB  - In constructing complete human chromosome maps, the relative order of markers and
      their precise chromosomal location will be combined. Multicolour in situ
      hybridisation, in which two probes are simultaneously hybridised to chromosomes
      and subsequently distinguished, potentially will provide both types of
      information. Using this technique, we have produced an ordered map of eight human
      chromosome 3 DNA markers, using small, single-copy probes that can detect target
      sequences ranging in size from 4 kb to as little as 500 bp.

PMID- 8275709
TI  - Segregation analysis of the mouse Rb(6.16) translocation in zygotes produced by
      heterozygous female carriers.
AB  - The segregation products in zygotes of females heterozygous for the mouse
      Rb(6.16) translocation were studied. Of 191 first-cleavage metaphase zygotes
      recovered from 16 females mated to chromosomally normal males, 132 were
      cytogenetically analyzed after sequential G- and C-banding. There were no
      products of adjacent segregation, since the six chromosomal imbalances were
      unrelated to the translocation. Alternate segregation was seen in 126 (95.5%) of
      the zygotes, with 85 being chromosomally normal and 41 carrying the
      translocation. These results indicate preferential alternate segregation and a
      significant deviation from the Mendelian 1:1 ratio (P < 0.005) for reciprocal
      alternate segregants, as seen earlier for males with this translocation. However,
      the approximately 2:1 ratio for normal-to-balanced segregants in females is lower
      than the ratios consistently seen for males. This supports the notion that there
      are different underlying causes of the distortion in the sexes.

PMID- 8275708
TI  - Regional mapping of the human NSP gene to chromosome region 14q21-->q22 by
      fluorescence in situ hybridization analysis.
AB  - Genetic sequences of the novel NSP gene, which encodes neuroendocrine-specific
      proteins, were isolated from cDNA libraries constructed with mRNA isolated from
      human lung carcinoma cells. Hybridization analysis of a panel of human x mouse
      cell hybrids with an 0.8-kb NSP cDNA probe indicated that the human NSP gene is
      probably located on chromosome 14. Fluorescence in situ hybridization analysis of
      metaphase chromosomes using overlapping genomic clones of NSP as a probe
      localized the NSP gene to chromosome region 14q21-->q22.

PMID- 8275710
TI  - A mouse chromosome 11 library generated from sorted chromosomes using linker
      adapter polymerase chain reaction.
AB  - We describe the generation of a mouse whole chromosome library using sequence
      independent polymerase chain reaction (PCR) to amplify sequences contained in DNA
      extracted from flow sorted chromosomes. DNA in sorted chromosomes from a human x
      mouse hybrid cell line was digested with a frequent four-cutter restriction
      enzyme, Sau3AI, and the ends were ligated to an adapter oligonucleotide. The
      ligated DNA fragments were amplified using PCR primers homologous to the linker
      adapter oligonucleotide. PCR-generated products were characterized by gel
      electrophoresis. The size of the amplified DNA ranged from 100 to more than 1,000
      bp with a relatively high proportion of products at approximately 400 bp.
      Biotinylated PCR products used for FISH showed specific hybridization to murine
      metaphases and no hybridization to human lymphocyte and hamster metaphase cells.
      Banding analysis indicated that the probes were specific for mouse Chromosome 11.
      We anticipate that availability of painting probes for specific murine
      chromosomes will facilitate cytogenetic studies in the mouse.

PMID- 8275711
TI  - A transfected human ribosomal RNA gene is present in the nucleolus of human
      cells.
AB  - Intraspecies transfection of ribosomal RNA genes (rDNA) into human fibroblasts
      was used to reexamine characteristics of the rDNA complex which lead to
      participation in nucleolar formation. Two constructs of human rDNA were analyzed.
      One included an intact transcribed spacer and promoter region and most of the
      nontranscribed spacer (NTS) region. The second contained the transcribed spacer
      and much of the NTS region, but lacked the transcription initiation region.
      Transfected rDNA, shown to be present in single or low copy number and containing
      the promoter region, was present in nucleoli. In contrast, transfected rDNA
      lacking the promoter did not participate in nucleolar organizing region (NOR)
      formation. We conclude from this study that tandem repetition, a feature of rDNA
      organization, is not an absolute requirement for rDNA function and that the
      presence of the rDNA transcription initiation region and promoter is necessary in
      establishing an active NOR.

PMID- 8275712
TI  - Transcription of rDNA is essential for satellite association.
AB  - A nonacrocentric human chromosome containing transfected human ribosomal DNA was
      analyzed for participation in nonrandom satellite associations with acrocentric
      chromosomes. Two constructs were tested. The first contained the complete rDNA
      transcriptional unit plus flanking DNA and was inserted at chromosome 3p13-->p12
      following transfection. The region was silver-positive indicating active
      transcription. The transcriptionally active rDNA participated in satellite
      association with other rDNA-bearing chromosomes at a rate 15% above random
      background associations. The second construct lacked the promoter region. This
      rDNA integrated at chromosome 4q31-->q32, and was silver stain-negative. Non
      random associations with other rDNA-bearing chromosomes were not observed. The
      study demonstrates that the DNA critical to nonrandom satellite associations is
      rDNA per se and that active transcription is a requirement.

PMID- 8275713
TI  - Chromosomal localization of two genes encoding human ras exchange factors: SOS1
      maps to the 2p22-->p16 region and SOS2 to the 14q21-->q22 region of the human
      genome.
AB  - The human SOS1 and SOS2 genes encode proteins that control GDP-->GTP exchange on
      ras proteins and are involved in signal transduction by tyrosine kinase
      receptors. In situ hybridization shows that SOS1 maps to 2p22-->p16 and SOS2 to
      14q21-->q22 in the human genome.

PMID- 8275714
TI  - The fucosyltransferase locus FUT1 maps distal to apolipoprotein loci E and C2 on
      human chromosome 19.
AB  - The location of the fucosyltransferase locus FUT1 relative to the apolipoprotein
      E/C2 loci on human chromosome 19 has remained unclear. We determined by a
      combination of physical mapping and fluorescence in situ hybridization that this
      fucosyltransferase gene maps distal to the apolipoprotein loci.

PMID- 8275716
TI  - High resolution mapping of the MYCN proto-oncogene at human chromosome 2p24.3 by
      fluorescence in situ hybridisation.
AB  - The MYCN proto-oncogene was previously mapped to human chromosome 2p24.1 by
      analysis of mouse x human somatic cell hybrids and radioactive in situ
      hybridisation to normal human chromosomes. However, using fluorescence in situ
      hybridisation (FISH) and high resolution chromosome banding techniques MYCN has
      been reassigned to 2p24.3.

PMID- 8275715
TI  - Chromosomal mapping of human CDK2, CDK4, and CDK5 cell cycle kinase genes.
AB  - Cyclin dependent kinases (CDK's) are kinases that interact with cyclins and
      regulate cell division. Genomic clones encoding human CDK2, CDK4, and CDK5 were
      obtained and mapped to their respective chromosomal loci using fluorescence in
      situ hybridization on human lymphocyte metaphase spreads. Interestingly, CDK2 and
      CDK4 were located at the same position, 12q13, and CDK5 was mapped to 7q36. 12q13
      has been shown to be associated with chromosome alterations such as
      amplifications and translocations in solid tumors. 7q36 does not appear to be a
      major site of chromosome alterations in tumors. As CDK2 and CDK4 appear to be
      important in regulating the human cell cycle, it is possible that the alterations
      of the 12q13 locus in tumors may involve changes in the regulation of CDK2 and
      CDK4 genes.

PMID- 8275717
TI  - Continuing medical education.

PMID- 8275718
TI  - Nasal intermittent positive pressure ventilation. Long-term follow-up in patients
      with severe chronic respiratory insufficiency.
AB  - Prior studies have shown that nasal intermittent positive pressure ventilation
      (NIPPV) can improve arterial blood gas values, prevent symptoms resulting from
      alveolar hypoventilation, and decrease hospitalization in patients with chronic
      respiratory failure. Most studies have involved small samples of patients
      followed up for a limited time. This study reviews our experience during 5 years
      use of NIPPV in 276 patients with kyphoscoliosis, posttuberculosis sequelae,
      Duchenne-type muscular dystrophy, COPD, and bronchiectasis followed up for > or =
      3 years while receiving NIPPV. Outcomes were compared for patients who survived
      short term eg, died or converted to management with a tracheostomy and
      intermittent positive ventilation (TIPPV) during year 1 or year 2 on a regimen of
      NIPPV and long term, eg, survived more > or = 2 years on a regimen of NIPPV. The
      most favorable outcome was achieved by patients with kyphoscoliosis and
      posttuberculosis sequelae with improvement in PaO2 and PaCO2 (p < 0.0001) and a
      reduction in days of hospitalization for respiratory illness (p < 0.0001) for >
      or = 2 years while receiving NIPPV. Patients with Duchenne-type muscular
      dystrophy also had fewer hospital days during NIPPV (p < 0.003) but only 9 of 16
      patients (56 percent) continued using NIPPV for the duration of followup. Benefit
      was also more short term for patients with COPD and bronchiectasis. NIPPV can
      sustain improvement in gas exchange, while reducing hospitalization for
      substantial periods of time. NIPPV can be an attractive and effective alternative
      to other methods of assisted ventilation such as TIPPV.

PMID- 8275719
TI  - Operating characteristics of 18 different continuous-flow jet nebulizers with
      beclomethasone dipropionate liposome aerosol.
AB  - A study of 18 different commercially available continuous-flow, jet nebulizers
      was performed with a standard liposomal formulation of beclomethasone
      dipropionate (Bec-DP) prepared with dilauroyl phosphatidylcholine (Bec-DLPC). The
      analysis compared the total Bec-DP output from aqueous suspensions of Bec-DLPC
      containing an initial starting reservoir concentration of 0.5 mg/ml. Aerosols
      from each nebulizer tested were characterized by the mass median aerodynamic
      diameter, geometric standard deviation, drug output, and the predicted percentage
      regional deposition of inhaled Bec-DLPC liposomes within the human respiratory
      tract. These data can provide a basis for the selection of commercially available
      jet nebulizers for use with glucocorticoid liposome aerosols for treatment of
      asthma and other inflammatory lung diseases.

PMID- 8275720
TI  - Medical personnel's knowledge of and ability to use inhaling devices. Metered
      dose inhalers, spacing chambers, and breath-actuated dry powder inhalers.
AB  - BACKGROUND: Current treatment strategies for asthma and chronic obstructive
      pulmonary disease (COPD) emphasize the inhalation route, yet patients often
      misuse metered-dose inhalers (MDI). To address this problem, patient education by
      medical personnel has been recommended and a variety of alternate inhaler devices
      have been developed. METHODS: We surveyed medical personnel to assess their
      knowledge of and ability to use three widely used inhaler devices; MDI, MDI with
      a spacing chamber (Aerochamber, Trudell Medical, Canada), and a breath-actuated
      multidose dry powder inhaler (Turbuhaler, Astra Pharmacy, Inc., Conada). Thirty
      respiratory therapists (RT), 30 registered nurses (RN), and 30 medical house
      staff physicians (MD) were asked to demonstrate the use of each device using
      placebo inhalers and to answer 11 clinically relevant questions related to the
      use and maintenance of the tested devices. RESULTS: The RT's percent mean
      knowledge score (67 +/- 5 percent) was significantly higher than those achieved
      by either the RNs (39 +/- 7 percent) or the MDs (48 +/- 7 percent) (for all p <
      0.0001). Similarly, percent mean demonstration scores for each device were
      significantly higher for RTs than either RN or MD groups; for MDI, 97 +/- 3
      percent versus 82 +/- 13 percent and 69 +/- 24 percent, respectively (p <
      0.0001); for the Aerochamber, 98 +/- 2 percent versus 78 +/- 20 percent and 57 +/
      31 percent (p < 0.0001); and for the Turbuhaler, 60 +/- 30 percent versus 12 +/-
      23 percent and 21 +/- 30 percent (p < 0.0001). Knowledge of and practical skills
      with the devices were roughly proportional to the length of time the device had
      been in clinical use, Turbuhaler demonstration scores being lower than either MDI
      or Aerochamber scores (p = 0.05 and p = 0.09, respectively). More RTs (77
      percent) had received formal instruction on the use of devices at school than
      either RNs (30 percent) or MDS (43 percent) (p < 0.05). CONCLUSION: We conclude
      that (1) many medical personnel responsible for monitoring and instructing
      patients in optimal inhaler use lack rudimentary skills with these devices, (2)
      nurses and physicians seldom receive formal training in the use of inhaling
      devices, and (3) newer inhaling devices designed to obviate problems of technique
      are at present less likely to be used well by medical personnel soon after their
      introduction.

PMID- 8275721
TI  - Changes in frequency spectra of breath sounds during histamine challenge test in
      adult asthmatics and healthy control subjects.
AB  - Air-flow standardized breath sounds were recorded at the chest and at the trachea
      during histamine challenge test and after subsequent bronchodilation in 12
      asthmatics and 6 healthy controls for spectral analysis, to be compared with
      simultaneous changes in spirometric variables. Of all the lung sound variables
      measured, the changes in median frequency of the power spectrum (F50) of tracheal
      expiratory sounds were found to correlate best (r = 0.853, p < 0.0001) with
      changes in FEV1. The increase of F50 during histamine challenge was significantly
      larger in asthmatics than in healthy control subjects (p < 0.005). The
      provocative dose of histamine inducing a decrease of 15 percent in FEV1
      (PD15FEV1) and the provocative dose causing an increase of 30 percent in tracheal
      expiratory F50 (PD30F50) were significantly related (r = 0.754, p = 0.012). In
      asthmatics, the breath sound frequency distribution in terms of median frequency
      reflected acute changes in airways obstruction with high sensitivity and
      specificity. The present method for breath sound analysis can be applied for
      patients with limited cooperation during bronchial challenge tests.

PMID- 8275722
TI  - Pleural plaques and risk for bronchial carcinoma and mesothelioma. A prospective
      study.
AB  - From the general population in the county of Uppsala, Sweden, 1,596 men with
      pleural plaques fulfilling strict radiologic criteria were identified from 1963
      until June 1985. The men have been followed prospectively for 16,369 person
      years. The number of mesotheliomas and bronchial carcinomas was compared with the
      age- and year-specific expected incidence from the official cancer registry of
      Sweden. Fifty bronchial carcinomas occurred, while 32.1 were expected after
      correction for smoking habits, a difference which was statistically significant.
      Patients with radiologic asbestosis were overrepresented among those with
      bronchial carcinoma. The risk for patients with pleural plaques without
      asbestosis was increased 1.4 times, which was statistically significant. There
      were 9 mesotheliomas, while only 0.8 were expected. The mean latency time from
      first exposure to diagnosis of bronchial cancer was 44.1 years and for
      mesothelioma was 48.1 years. Thus, pleural plaques on the chest roentgenogram
      indicate significant exposure to asbestos, with an increased risk for
      mesothelioma and possibly also for bronchial carcinoma. Any person found to have
      plaques on chest roentgenogram should be informed of them and should be persuaded
      to stop smoking.

PMID- 8275723
TI  - The relation of sleep complaints to respiratory symptoms in a general population.
AB  - Based on data obtained from the Tucson Epidemiologic Study of Chronic Lung
      Disease that included body weight, questionnaire responses, and spirometry, we
      found that among subjects with no respiratory symptoms, 28.0 percent reported
      insomnia (difficulty initiating or maintaining sleep) and 9.4 percent reported
      daytime sleepiness. Among subjects with respiratory symptoms, cough and/or
      wheeze, the rates of sleep complaints increased. With one symptom, 39.1 percent
      reported insomnia and 12.4 percent reported daytime sleepiness. With both
      symptoms, the rates were 52.8 percent and 22.8 percent, respectively. Overall, we
      found significant relationships between rates of respiratory symptoms and sleep
      complaints (trend chi 2 = 73.9, p < 0.001 for insomnia; trend chi 2 = 37.9, p <
      0.001 for daytime sleepiness). In separate analyses, obesity, snoring, and a
      diagnosis of lung disease also influenced the rate of sleep complaints but, when
      we employed logistic regression, we found that obesity, respiratory symptoms,
      gender, and age were the only variables related to the risk of insomnia or
      daytime sleepiness.

PMID- 8275724
TI  - Long-term survival of patients with obstructive sleep apnea treated by
      uvulopalatopharyngoplasty or nasal CPAP.
AB  - Patients with obstructive sleep apnea (OSA) have decreased long-term survival.
      Treatment of OSA with either nasal continuous positive airway pressure (CPAP) or
      tracheostomy improves survival, but the effect of uvulopalatopharyngoplasty
      (UPPP) on survival is unclear. We attempted to contact all patients with OSA
      treated with either UPPP or nasal CPAP over a 6-year period to compare long-term
      survival between these two treatments. One hundred fifty-four patients had a UPPP
      during this period. Five of these patients were later treated with nasal CPAP and
      were excluded from the analysis. Twelve of the remaining 149 were unavailable for
      follow-up but were included in the analysis. Follow-up polysomnography was
      performed on 140 (94 percent) of these patients; 114 (81 percent) had either a
      postoperative apnea index < 5/h or > 50 percent reduction in apnea index. Two
      hundred eight patients were started on a regimen of nasal CPAP during the same
      period. Eighty-two patients discontinued nasal CPAP therapy and were excluded
      from analysis. Nine of the remaining 126 were unavailable for follow-up but were
      included in the analysis. Six patients treated with UPPP died. Three of these six
      patients had a 3-month follow-up polysomnogram that revealed apnea indices of
      1/h, 5/h, and 23/h. Three patients treated with nasal CPAP died. There was no
      difference in the long-term survival between the two treatment groups. We
      conclude that there may be no difference in the long-term survival of patients
      with OSA between those treated with UPPP and those treated with nasal CPAP. This
      study emphasizes the importance of follow-up polysomnography in all patients
      after UPPP.

PMID- 8275725
TI  - A laboratory validation study of a portable system for remote recording of sleep
      related respiratory disorders.
AB  - This study represents the validation of an out-of-laboratory recording system for
      screening sleep disorders by comparing it to an in-laboratory system which
      accomplishes complete polysomnography. Forty patient cases were collected. Each
      patient slept in the sleep laboratory with the simultaneous monitoring of eight
      channels from the Sleep I/T (CNS, Inc), as well as complete polysomnographic
      monitoring comparable to that which accomplishes routine patient evaluations
      utilizing the Sleeplab (CNS, Inc) system. The data collected on the Sleeplab
      system were analyzed in a computer-assisted manner followed by manual overreading
      of the raw data. The Sleep I/T data analysis was performed automatically using
      default parameters. The results revealed no significant differences in the
      determination of sleep efficiency, respiratory disturbance index (RDI), periodic
      leg movement (PLM) index, or the desaturation index. For the RDI, the sensitivity
      was 100 percent and the specificity was 93 percent for correctly detecting an RDI
      of 15 per hour, and the PLM index had a sensitivity of 89 percent and specificity
      of 97 percent in detecting episodes greater than 20 per hour. These data
      demonstrate excellent agreement between this out-of-laboratory system and
      polysomnography in its ability to detect accurately RDI, PLM index, and
      saturation levels.

PMID- 8275726
TI  - Reanalysis of the 12-minute walk in patients with chronic obstructive pulmonary
      disease.
AB  - The purpose of this study was to determine the correlation between different
      intervals in the 12-min walk test, to determine which of the intervals best
      correlated with maximal oxygen intake (VO2max) and maximal CO2 expelled (VCO2max)
      and to determine the degree of correlation between changes in the VO2max and
      changes in the walk test and spirometry. Nine elderly (age, 67 +/- 4 years)
      patients with moderate COPD (FEV1, 1.32 +/- 0.28 L) who were ventilatory limited
      were seen 6 times over a 14-week period. At each visit they performed spirometry,
      a 12-min walk, and a symptom-limited maximal exercise test. During the 12-min
      walk the distances traversed in each 2-min interval were recorded. A Borg score
      was obtained at the end of each 2 min. The distances that the patients walked in
      each 2-min interval were very similar, but the mean Borg score became higher the
      longer the patient walked. The Borg score after 2 min was 1.64 +/- 1.15, while
      the Borg score after 12 min was 5.70 +/- 3.59. The correlation coefficients
      between the distance walked at various intervals and the oxygen consumption
      (VO2)/kg (approximately 0.65) and the VCO2/kg (approximately 0.52) were very
      similar. However, changes in the VO2/kg were more closely correlated with changes
      in the 12-min walk (r = 0.72), than with changes in the 6-min walk (r = 0.64),
      the 4-min walk (r = 0.59), or the 2-min walk (r = 0.53). This latter observation
      suggests that the 12-min walk may be preferable to tests in which the patient
      walks 4 or 6 min for documenting changes in the exercise capabilities.

PMID- 8275728
TI  - Ontogeny of a human polychlorinated biphenyl-binding protein. Level of expression
      in tracheal aspirates in bronchopulmonary dysplasia.
AB  - A human lung polychlorinated biphenyl binding protein (PCB-BP,M(r) 13 kd) has
      recently been purified from lavage fluid. Polyclonal monospecific antibodies
      against PCB-BP were produced and used for immunohistochemical staining in
      sections of human lung tissue. PCB-BP was found to localize preferentially to the
      nonciliated (Clara) cells of the lung, whereas the alveolar cells and ciliated
      cells of the larger airways were devoid of staining. Tracheal aspirates from
      infants receiving mechanical ventilation were subjected to sodium dodecyl sulfate
      polyacrylamide gel electrophoresis separation and Western immunoblotting. The
      antibodies to human PCB-BP detected a single band of the expected molecular
      weight, and a quantitative analysis of the ontogeny of PCB-BP in tracheal
      aspirates was performed by construction of Western immunoblot standard curves. A
      significant increase in the levels of PCB-BP in late gestation (gestational weeks
      39 to 41) was demonstrated. In similar experiments, levels of PCB-BP in tracheal
      aspirates obtained from infants with bronchopulmonary dysplasia (BPD) at the
      postconceptional age of less than 38 weeks were found to be significantly
      elevated as compared with a normal study group of similar gestational age (21.8
      +/- 4.8 vs 3.1 +/- 0.8 ng of PCB-BP per microgram of total protein, p < 0.005).
      It is suggested that the high levels of PCB-BP at the postconceptional age of
      less than 38 weeks observed in infants with BPD may reflect inflammatory injury
      and regeneration of airway epithelium, associated with proliferation of Clara
      cells.

PMID- 8275727
TI  - Graded comprehensive cardiopulmonary exercise testing in the evaluation of
      dyspnea unexplained by routine evaluation.
AB  - The evaluation of dyspnea is problematic when a cause is inapparent after initial
      diagnostic studies. We examined the results and role of cardiopulmonary exercise
      testing (CPET) in 50 patients with a mean 23 months of dyspnea and normal FEV1
      and FVC. The CPET studies were interpreted by a panel and a consensus reached.
      Subsequent tests ordered by the primary physician were reviewed, and a final
      diagnosis was agreed on by the panel. Seven of 50 patients had cardiac
      limitation, 17 of 50 had pulmonary limitation, 14 of 50 had obesity and/or
      deconditioning, 1 of 50 had gastroesophageal reflux, and 16 of 50 had either
      psychogenic dyspnea or no identifiable disease. Five patients had more than one
      clinical diagnosis accounting for 55 diagnoses in the 50 patients. Those with a
      normal CPET had a higher VO2max and O2 pulse than those with cardiac disease,
      deconditioning, or hyperactive airways disease (HAD) (p < 0.05).
      Electrocardiographic changes identified cardiac disease while studies
      demonstrating ventilatory limitation identified a pulmonary process. In 24,
      deconditioning could not be distinguished from cardiac limitation. Of these, 14
      responded to exercise training and/or weight loss, whereas 3 had cardiac disease,
      7 had HAD, and 4 had psychogenic dyspnea (4 had more than one clinical
      diagnosis). In the 13 patients with normal CPET results, one had gastroesophageal
      reflux, two had HAD, four had psychogenic dyspnea, and six had no identifiable
      disease. We conclude that a diagnosis can be made in most patients with chronic
      dyspnea; however, further studies including bronchoprovocation are often
      required. Cardiopulmonary exercise testing is useful in identifying a cardiac or
      pulmonary process, but it is insensitive in distinguishing cardiac disease from
      deconditioning.

PMID- 8275729
TI  - Spirometric impairments in long-term insulators. Relationships to duration of
      exposure, smoking, and radiographic abnormalities.
AB  - A study of 2,611 long-term asbestos insulators was well suited to provide
      information on (1) the prevalence of spirometric impairments in a large, well
      defined population and (2) the effects of cigarette smoking, radiographic
      abnormalities, and duration from onset of exposure on pulmonary function.
      Prevalences are reported by a mutually exclusive classification of impairments
      (normal, restrictive, obstructive, small airways, and combined) as well as by
      abnormality of specific spirometric tests (FVC, FEV1/FVC, and midexpiratory
      time). Only 3 percent of nonsmokers (NS) had obstruction and 6 percent a
      decreased FEV1/FVC. Frequency of restriction did not vary by smoking history; it
      was 31 percent in NS and current smokers (CS) and 34 percent in ex-smokers (XS).
      Obstruction (present in 17 percent) and combined impairment (in 18 percent) were
      most common in CS. The FEV1/FVC was decreased in 35 percent of CS and 18 percent
      of XS. The FVC was decreased in 49 percent of CS, 44 percent of XS, and 33
      percent of NS. Normal spirometry was most common when the radiograph was normal
      (almost half the workers with normal radiographs had normal spirometry).
      Nevertheless, FVC was reduced in 27 percent of those with normal radiographs and
      a normal radiograph was seen in 11 percent of workers with restriction.
      Restrictive and combined impairments were most frequent when both parenchyma and
      pleura were abnormal. Restriction was more frequent in isolated pleural disease
      (seen in 34 percent such subjects) than in isolated parenchymal disease (22
      percent). The contribution of pleural fibrosis to reduced FVC and of asbestos
      exposure and smoking both to reduced FVC and to reduced FEV1/FVC was confirmed by
      regression analysis. That reduced FVC and reduced FEV1/FVC are both more frequent
      in insulators who have smoked (compared with NS insulators or smokers in the
      general population) suggests an interaction between asbestos and smoking in
      producing both these physiologic abnormalities.

PMID- 8275730
TI  - Dead space loading and exercise limitation in patients with interstitial lung
      disease.
AB  - STUDY DESIGN: We tested the hypothesis that maximal exercise performance in
      subjects with interstitial lung disease (ILD) is limited by respiratory factors.
      Assuming this is so, ventilatory stimulation by added dead space (VD) should
      impair exercise capacity. METHODS: Six subjects with ILD each underwent three
      maximal incremental exercise studies on a bicycle ergometer; control 1, added VD,
      and control 2. During the VD study, external VD (500 ml) was added to the
      circuit, and results obtained were compared with the mean results from the
      control studies. RESULTS: Exercise duration (TLIM) was significantly less in the
      VD study when compared to the control study (369 +/- 50 vs 439 +/- 55, p < 0.05),
      as was work rate (102 +/- 13 vs 125 +/- 14 W, p < 0.05) and peak oxygen uptake
      per minute (VO2) (1.08 +/- 0.09 vs 1.43 +/- 0.14 L/min, p < 0.05). At end
      exercise, the Borg scale was higher in the VD study when compared to the control
      study (6 +/- 1 vs 5 +/- 1, p < 0.05), while no significant difference in minute
      ventilation (VI) or oxygen desaturation was noted. When compared to the control
      study at matched times during exercise, the addition of VD resulted in a
      significant increase in VI while no significant change was noted in VO2, carbon
      dioxide output (VcO2), or heart rate (HR). CONCLUSION: The decrease observed in
      TLIM, work rate, and peak VO2 with added VD, associated with a lack of change in
      VI or oxygen desaturation at end-exercise, suggests that exercise limitation in
      ILD is primarily due to respiratory factors.

PMID- 8275731
TI  - N-acetylcysteine enhances recovery from acute lung injury in man. A randomized,
      double-blind, placebo-controlled clinical study.
AB  - OBJECTIVE: To determine the effects of intravenous N-acetylcysteine (NAC) on the
      development of severe adult respiratory distress syndrome (ARDS) and mortality
      rate in patients with mild-to-moderate acute lung injury and to analyze the
      duration of ventilatory support and FIO2 required as well as the evolution of the
      lung injury score. SETTING: Three university hospital ICUs and one regional ICU
      in Switzerland. PATIENTS: Sixty-one adult patients presenting with mild-to
      moderate acute lung injury and various predisposing factors for ARDS received
      either NAC, 40 mg/kg/d, or placebo intravenously for 3 days. MEASUREMENTS:
      Respiratory dysfunction was assessed daily according to the need for mechanical
      ventilation and FIO2, the evolution of the lung injury score, and the PaO2/FIO2
      ratio. The cardiovascular state, liver function, and kidney function were also
      monitored. Data were collected at admission (day 0), during the first 3 days, and
      on the day of discharge from the ICU. RESULTS: The NAC and placebo groups (32 and
      29 patients, respectively) were comparable at ICU admission for severity of
      illness assessed by the simplified acute physiology score (SAPS) (10.8 +/- 4.6 vs
      10.9 +/- 4.8) and lung injury score (LIS) (1.39 +/- 0.95 vs 1.11 +/- 1.08) (mean
      +/- SD). Three patients in each group developed ARDS. The 1-month mortality rate
      was 22 percent for the NAC group and 35 percent for the placebo group (difference
      not statistically significant). At admission, 22 of 32 patients (69 percent) in
      the NAC group were mechanically ventilated compared with 22 of 29 (76 percent) in
      the placebo group. At the end of the treatment period (day 3), 5 of 29 (17
      percent) in the NAC group and 12 of 25 (48 percent) in the placebo group were
      still receiving ventilatory support (p = 0.01), The FIO2 was 0.37 less than
      admission value (day 0) in the NAC group, and 0.20 less in the placebo group (p <
      0.04); the oxygenation index (PaO2/FIO2) improved significantly (p < 0.05) from
      day 0 to day 3 only in the NAC-treated group. The LIS showed a significant
      regression (p = 0.003) in the NAC-treated group during the first 10 days of
      treatment: no change was observed in the placebo group. No adverse effects were
      observed during the treatment with NAC. CONCLUSIONS: Intravenous NAC treatment
      during 72 h improved systemic oxygenation and reduced the need for ventilatory
      support in patients presenting with mild-to-moderate acute lung injury subsequent
      to a variety of underlying diseases. Development of ARDS and mortality were not
      reduced significantly by this therapy.

PMID- 8275732
TI  - Chylothorax in Gorham's syndrome. A common complication of a rare disease.
AB  - One hundred forty-six cases of Gorham's syndrome are documented in the
      literature. Twenty-five (17 percent) patients have been reported to have
      chylothorax as a complication. To our knowledge, this high incidence of
      chylothorax has not been reported previously. We describe two such patients
      treated by thoracic duct ligation and compared our results with others to support
      early surgical intervention via a low right-sided thoracotomy in these cases.

PMID- 8275733
TI  - Efficiency of bronchodilator aerosol delivery to the lungs from the metered dose
      inhaler in mechanically ventilated patients. A study comparing four different
      actuator devices.
AB  - STUDY OBJECTIVE: To compare aerosol delivery to the lungs in ventilated patients
      from two devices with holding chamber and two devices without holding chamber.
      DESIGN: A controlled clinical trial with randomization to one of four delivery
      devices. SETTING: An academic university-affiliated Canadian ICU. PATIENTS: Forty
      eight patients undergoing mechanically assisted ventilation for a variety of
      clinical reasons and each judged to require inhaled bronchodilator therapy by the
      attending physician. INTERVENTIONS: Patients received 4 puffs of fenoterol
      labeled with technetium 99m pertechnetate delivered by metered-dose inhaler via 1
      of the following: A, a 167-ml chamber device; B, a 700-ml chamber device; C, a
      nonchamber device (A, B, and C, all in the ventilator inspiratory line); and D, a
      nonchamber device on the end of the endotracheal tube. MEASUREMENTS AND RESULTS:
      One-minute images of the thorax were made by a portable gamma camera at the
      bedside. Deposition of radioactivity in the lungs (uncorrected for tissue
      absorption and calculated as a percentage of the radioactivity delivered from 4
      puffs) was 5.53 +/- 0.72 (mean +/- 1 SEM), 6.33 +/- 1.16, 1.67 +/- 0.43, and 3.89
      +/- 0.52 percent for devices A, B, C, and D, respectively (p = 0.004). Subgroup
      analysis showed a statistically significant difference in delivery between
      devices A and C and between devices B and C only. CONCLUSION: There were
      statistically significant differences between delivery from both chamber devices
      and the inline nonchamber device, but not between delivery from other devices.
      Further work will be necessary to determine the effect of device position in the
      ventilator circuit on aerosol delivery.

PMID- 8275734
TI  - Relationship between expired capnogram and respiratory system resistance in
      critically ill patients during total ventilatory support.
AB  - To examine the relationship of expired capnograms and respiratory system
      resistance (Rrs) in intubated critically ill patients, we consecutively studied
      41 mechanically ventilated patients to (1) analyze the association between
      expired CO2 slope and auto-positive end-expiratory pressure (auto-PEEP), between
      Rrs and auto-PEEP, between Rrs and expired CO2 slope, and between Rrs and
      arterial minus end-tidal PCO2 gradient (PaCO2-PETCO2 gradient) and (2) to
      investigate the capacity of the expired CO2 slope and PaCO2-PETCO2 gradient to
      predict Rrs during mechanical ventilation. Regression analysis found a close
      correlation between Rrs and expired CO2 slope (r = 0.86; p < 0.001), between Rrs
      and auto-PEEP (r = 0.75; p < 0.001), and between auto-PEEP and expired CO2 slope
      (r = 0.74; p < 0.001). Weak correlation was found between Rrs and PaCO2-PETCO2
      gradient (r = 0.48; p < 0.01). Prediction interval limits at 95 percent
      confidence level for Rrs are approximately +/- 7.39 cm H2O/L/s from the predicted
      value obtained by the regression equation, where Rrs = 11.42 + 2.28 expired CO2
      slope. These observations suggest that CO2 elimination in critically ill patients
      is strongly modulated by lung, airway, endotracheal tube, and ventilator
      equipment resistances. Although continuous capnogram waveform monitoring at the
      bedside might be useful to assess Rrs, very accurate predictions could be done
      only in determinate patients.

PMID- 8275735
TI  - Risk factors for early onset pneumonia in trauma patients.
AB  - STUDY OBJECTIVES: The aim of the study was to identify risk factors for early
      onset pneumonia (EOP) in trauma patients, in order to seek possible intervention
      strategies. STUDY POPULATION: Participants included 124 consecutive trauma
      patients admitted to a general intensive care unit (ICU) of a university hospital
      from December 1990 to February 1992 inclusive. DATA COLLECTION: The following
      data were prospectively collected for each patient: demographics, severity of
      trauma according to the abbreviated injury scale (AIS), severity of coma
      according to the Glasgow coma scale (GCS), presence of pneumothorax, pulmonary
      contusion, rib fractures, hemothorax, and mechanical ventilation. All patients
      were monitored daily during the ICU stay for the onset of pneumonia, sepsis
      syndrome, septic shock, and adult respiratory distress syndrome (ARDS). Criteria
      for the diagnosis of pneumonia were: core temperature of greater than 38.3
      degrees C, a WBC count of 10,000 cells/mm3, purulent tracheobronchial secretions,
      a worsening of pulmonary gas exchange, and persistent pulmonary infiltrates. All
      patients with suspected pneumonia underwent quantitative bronchoalveolar lavage
      (BAL) as well as blood cultures; BAL cultures were considered positive when they
      showed bacterial growth greater than 1 x 10(5) colony-forming unit (cfu)/ml, or
      less than 10(5), but with the same microorganism isolated in blood cultures.
      Pneumonia occurring within the first 96 h after trauma was considered EOP. DATA
      ANALYSIS: A stepwise logistic regression analysis was carried out in order to
      identify factors independently associated with an increased risk of EOP and late
      onset pneumonia (LOP). RESULTS: Overall mortality was 43.5 percent: mortality
      increased by age and AIS score. Forty one patients (33.1 percent) developed
      pneumonia: 26 (63.4 percent) were EOP and 15 (36.6 percent) were LOP. In the
      univariate analysis, an age greater than 40 years, the presence of pulmonary
      contusion, AIS of more than 4 for thorax and of more than 9 for abdomen, and the
      absence of mechanical ventilation (MV) during the first 4 days of hospitalization
      or MV lasting less than 24 h were significantly associated with an increased risk
      of acquiring EOP. Logistic regression analysis showed that the strongest risk
      factor for EOP was a combined severe abdominal and thoracic trauma, which
      increased the risk of EOP by 11 times; an age of more than 40 years and MV of
      less than 24 h during the first 4 days of hospitalization were also independent
      risk factors for EOP. Factors associated with LOP were an AIS score of more than
      4 for abdomen and a length of MV of more than 5 days. CONCLUSION: In a trauma
      population, a combined severe abdominal and thoracic trauma represents a major
      risk factor for EOP. Mechanical ventilation administered during the first days
      after trauma seems to reduce the risk of EOP. As reported in previous studies,
      mechanical ventilatory support lasting more than 5 days is associated with an
      increased risk of LOP.

PMID- 8275736
TI  - Management of acute respiratory failure due to pulmonary edema with nasal
      positive pressure support.
AB  - The management of patients with respiratory failure from cardiogenic pulmonary
      edema may require intubation and mechanical ventilation. This provides both
      ventilatory assistance as well as the beneficial hemodynamic effects of positive
      intrathoracic pressure. As the need for ventilation is usually short term,
      noninvasive ventilatory support may be adequate. We report the use of biphasic
      positive airway pressure by nasal mask (BiPAP system) to successfully manage two
      patients with respiratory failure due to pulmonary edema.

PMID- 8275737
TI  - The effects of biofeedback assisted breathing retraining on lung functions in
      patients with cystic fibrosis.
AB  - This study examines the effects of respiratory muscle feedback and breathing
      retraining (BRT) on lung function in patients with cystic fibrosis (CF). Twenty
      six patients with CF were matched for age and severity of disease. Standard
      respiratory spirometry was performed on all subjects before and after biofeedback
      training. Thirteen experimental subjects underwent eight sessions of
      pneumographic or strain-gauge feedback from the abdominal muscles and
      electromyogram feedback from accessory respiratory muscles to assist in learning
      diaphragmatic and pursed-lips breathing maneuvers. Control subjects received
      biofeedback-assisted (hand warming) relaxation training. Results revealed a
      significant improvement in FEV1 and mean forced expiratory flow during the middle
      half of forced vital capacity (FVC) for the biofeedback group, while the control
      group showed no change. A similar trend was noted for FVC. These data suggest
      that respiratory muscle feedback and BRT may improve lung function in patients
      with CF.

PMID- 8275738
TI  - Urine hydrogen peroxide during adult respiratory distress syndrome in patients
      with and without sepsis.
AB  - BACKGROUND: The lung injury in adult respiratory distress syndrome (ARDS) has
      been associated with increased expiratory hydrogen peroxide (H2O2)
      concentrations. Furthermore, patients with sepsis and ARDS are reported to have
      greater serum scavenging of H2O2 than patients with ARDS only. We hypothesized
      that the systemic presence of H2O2 would be detectable in the urine of these two
      groups of patients and that, in the case of ARDS sepsis, the relative
      contribution of each disease to the production this analyte would be discernible.
      Accordingly, we used an in vitro radioisotope assay to follow the weekly course
      of urine H2O2 levels in ARDS patients with and without sepsis, and in samples
      from control non-ARDS patients with sepsis with indwelling urinary catheters and
      in samples provided by healthy volunteers. METHODS: Thirty patients with ARDS
      were included in the study: 23 had sepsis and 7 were sepsis free. An indwelling
      catheter was used to collect urine from each patient over a 24-h period, first
      within 48 h of ICU admission and then every seventh day over the course of their
      illness. Urine H2O2 was measured by competitive decarboxylation of 1-14C-alpha
      ketoglutaric acid by H2O2. Urine samples were provided by 20 healthy volunteers
      while, in 10 non-ARDS patients with sepsis, urine was collected over one 24-h
      period following a 5-day minimum with an indwelling urinary catheter. RESULTS:
      Urine H2O2 concentration in healthy control subjects (88 +/- 4 mumol/L) and non
      ARDS patients with urinary catheters (96 +/- 5 mumol/L) was not significantly
      different. During the first 48 h in the ICU, urine H2O2 in patients with ARDS
      only (295 +/- 29 mumol/L) was significantly lower (p < 0.05) than patients with
      ARDS and sepsis (380 +/- 13 mumol/L); however, the lung injury scores of these
      two groups did not differ. Furthermore, within the first 48 h, the urine H2O2 of
      the patients with ARDS and sepsis who did not survive (427 +/- 19 mumol/L; n = 7)
      was significantly higher than that in patients who survived sepsis (352 +/- 14
      mumol/L; n = 15). Thereafter, the lung injury scores and urine H2O2 levels of the
      nonsurvivor ARDS-sepsis group remained significantly higher compared with the
      other two groups. At lung injury scores of 3 and 2, regardless of days in ICU,
      the patients with ARDS only had significantly lower urine H2O2 (266 +/- 30
      mumol/L and 167 +/- 24 mumol/L, respectively) compared with the survivor ARDS
      sepsis group (376 +/- 19 mumol/L and 250 +/- mumol/L). When the patients with
      ARDS (both ARDS only and with sepsis) recovered, their urine H2O2 concentration
      did not differ from the control groups (healthy donors and patients without
      ARDS). CONCLUSION: Lung injury scores did not differentiate patients with ARDS
      and sepsis from patients with ARDS only during the first 10 days in the ICU;
      however, urine H2O2 levels were significantly greater in the patients with ARDS
      and sepsis. Moreover, despite no initial difference in lung injury, patients who
      did not survive ARDS and sepsis had consistently greater urine H2O2 concentration
      than patients who survived sepsis. The urine H2O2 level in the ARDS-only group
      was about 70 percent of the level in the survivor ARDS and sepsis group,
      suggesting that ARDS alone is the major contributor to the H2O2 oxidant processes
      during combined ARDS and sepsis. Furthermore, these studies demonstrate that
      urine H2O2 may be a useful analyte to differentiate the severity of oxidant
      processes in patients with ARDS and sepsis albeit the prognosis appears to be
      survival or nonsurvival.

PMID- 8275739
TI  - Mucociliary transport in ICU patients.
AB  - OBJECTIVES: The objectives of this study were to determine the bronchial mucus
      transport velocities in ventilated ICU patients and to study the possible role of
      impaired mucus transport in the development of retention of secretion and
      pneumonia. DESIGN: The patients were studied prospectively in a convenience
      sample trial. SETTING: The study took place at a university hospital. PATIENTS:
      Thirty-two ventilated patients in a surgical ICU were included in the study. The
      study was approved by the Ethics Committee of the University of Ulm.
      INTERVENTIONS: Bronchial mucus transport velocity (BTV) was measured with a small
      volume of technetium 99m-labeled albumin microspheres within the first 3 days of
      mechanical ventilation. The radiolabeled bolus was deposited at the distal end of
      the right and left main bronchus via flexible bronchoscopy. The movement of the
      microspheres toward the trachea was visualized and recorded using a scintillation
      camera. After determination of BTV, the patients were examined daily for 4 days
      to record pulmonary complications (defined as retention of secretion and
      nosocomial pneumonia). MAIN MEASUREMENTS AND RESULTS: The median BTV in the right
      primary bronchus was 0.8 mm/min and in the left it was 1.4 mm/min. In nine
      patients both radioactive drops remained at the application site. In 14 patients,
      a total of 19 pulmonary complications occurred (10 times retention of secretion,
      9 times pneumonia). Patients with pulmonary complications had statistically
      significant lower BTV compared with patients without pulmonary complications; in
      the left bronchus 0 (0 to 6.5) mm/min (median with range) vs 3.5 (0 to 10.5)
      mm/min (p < 0.01) and in the right bronchus 0 (0 to 3.0) mm/min vs 4.7 (0 to
      11.7) mm/min (p < 0.01). CONCLUSIONS: Ventilated patients in the ICU frequently
      have impaired mucus transport, which is associated with the development of
      retention of secretion and pneumonia.

PMID- 8275740
TI  - Peak airway pressure: why the fuss?
AB  - The preponderance of evidence indicates that high airway pressure is not by
      itself injurious to the lung. Rather, overdistention of the lung appears to be
      the fundamental mechanism underlying VALI. The physician must bear in mind the
      factors (ie, flow-resistive pressure losses, respiratory muscle activity, and
      abnormalities in rib cage or abdominal compliance) that may alter the
      relationship between PAP and lung volume. Under some circumstances, high PAP may,
      in fact, reflect lung overdistention, and maneuvers that minimize overdistention
      may also reduce PAP. Similarly, the goal of improving oxygenation may sometimes
      entail strategies (such as prolonging inspiratory time) that lower PAP. In these
      settings, however, the reduction in PAP should be regarded as a by-product of
      achieving another therapeutic goal and not an end point in and of itself. In
      other settings, such as the mechanically ventilated patient with severe airflow
      obstruction, measures that lower PAP by reducing inspiratory flow rate may worsen
      pulmonary hyperinflation, and thereby increase the risk of complications.

PMID- 8275741
TI  - Oxygen conserving methods for adults.

PMID- 8275742
TI  - A large air-filled cyst in a patient with migratory infiltrates.

PMID- 8275743
TI  - University of Wisconsin solution extends lung preservation after prostaglandin E1
      infusion.
AB  - University of Wisconsin (UW) solution has been demonstrated to enhance and extend
      the preservation of the hepatic, pancreatic, renal, and cardiac allografts.
      Prostaglandin E1 (PGE1), which has been used to produce pulmonary vasodilatation,
      has improved preservation in lung transplantation. Experiments were designed to
      evaluate their potential role in 24-h preservation of the allografts in lung
      transplantation. Thirty-six dogs underwent left lung transplantation. The donor
      lungs (n = 6 in each group) were flushed with UW solution (group 1 and 2) or
      modified Euro-Collins (EC) solution (group 3) after PGE1 infusion (500
      micrograms). In group 1, donor lungs were transplanted immediately. Lung
      allografts of group 2 and 3 were cold stored (4 degrees C) in the same
      preservation solution for 24 h in the inflated state and then transplanted. The
      right pulmonary artery and right main bronchus were ligated 1 h after completion
      of the transplantation, forcing the recipient dogs to survive with the
      transplanted left lung. The recipients were ventilated with an inspired oxygen
      fraction of 0.4 and end-expiratory pressure 10 cm H2O. Two dogs died prematurely
      in group 3, whereas all dogs in group 1 and 2 survived the experimental period.
      The arterial oxygen tension and saturation and dynamic lung compliance were
      significantly higher in dogs of group 1 and 2. Transplanted lungs of group 1 and
      2 had significantly lower pulmonary vascular resistance, alveolar-arterial oxygen
      difference, and wet/dry lung weight ratio. Histologically, pulmonary edema,
      congestion, sloughing of bronchial mucosa, and peribronchial and peripulmonary
      arterial hemorrhage were shown in lungs of group 3, but not in those of group 1
      and 2. Airway mucosa and pulmonary vascular structure were well preserved in
      lungs of group 1 and 2. There was no significant difference between group 1 and 2
      in lung functions, hemodynamics, or morphologic features. We concluded that PGE1
      and UW solution could effectively extend lung preservation up to 24 h in this in
      vivo canine lung allotransplantation model.

PMID- 8275744
TI  - Trainability of arms versus legs in men previous myocardial infarction.

PMID- 8275745
TI  - Dyspnea, cough, and interstitial lung disease in a 32-year-old smoker.

PMID- 8275746
TI  - Role of the coagulation system in ARDS.

PMID- 8275747
TI  - Uvulopalatopharyngoplasty and inferior sagittal mandibular osteotomy with
      genioglossus advancement for treatment of obstructive sleep apnea.
AB  - We prospectively studied nine patients with the obstructive sleep apnea (OSA)
      syndrome with polysomnography before and after combined (seven simultaneous and
      two sequential) uvulopalatopharyngoplasty and inferior sagittal mandibular
      osteotomy with genioglossus advancement as treatment for OSA. All patients had
      failed to tolerate nasal continuous positive airway pressure and had a
      respiratory disturbance index (RDI) > or = 20. All patients were found to have
      disproportionate pharyngeal anatomy with airway narrowing by cephalometrograms
      and/or fiberoptic nasopharyngoscopy. Following surgery there were significant
      reductions in the average numbers of respiratory events and significant
      improvements in average oxygen saturation measurements. When RDIs < or = 5 and <
      or = 10 are chosen as objective success benchmarks, the success rates are 67
      percent (6/9) and 78 percent (7/9), respectively.

PMID- 8275748
TI  - Gossypibomas mimicking echinococcal cyst disease of the lung.
AB  - Gossypibomas, masses of retained cotton materials, may produce a variety of
      postoperative complications. This case report of hemoptysis of 18 months'
      duration and cavitating chest masses in a 62-year-old man with previous cardiac
      operations illustrates several salient features about the presentation,
      differential diagnosis, and management of gossypibomas.

PMID- 8275749
TI  - Transesophageal echocardiographic assessment of aortic coarctation using color,
      flow-directed Doppler sampling.
AB  - We report the use of color, flow-directed transesophageal Doppler in the
      evaluation of aortic coarctation. Transesophageal echocardiography (TEE) was used
      to define the aortic shelf in two adults with mild and moderate postductal
      coarctation, respectively. The color mosaic pattern aided in identification of
      the coarctation location and orifice diameter. Continuous wave and pulsed cursors
      were steered to provide sampling parallel to the color jet direction and
      gradients calculated by the modified Bernoulli formula, excluding prestenotic
      velocities. Measured pressure gradients were equivalent to those determined at
      catheterization. We conclude that color, flow-directed TEE Doppler sampling can
      aid in the identification and characterization of adult patients with aortic
      coarctation.

PMID- 8275750
TI  - Mucosa-associated lymphoid tissue lymphoma of the lung with cold-reacting
      autoantibody-mediated hemolytic anemia.
AB  - Mucosa-associated lymphoid tissue lymphoma (MALT-oma) of the lung is a rare low
      grade B cell lymphoma arising from bronchus-associated lymphoid tissue. This
      report concerns a 39-year-old woman with bilateral diffuse alveolar
      consolidations and cold-reacting autoantibody-mediated hemolytic anemia. Open
      lung biopsy showed angulated lymphoid cells with lymphoepithelial lesions.
      Immunocytochemistry revealed that the lymphoid cells were positive for CD19,
      CD20, and IgM (lambda), which was consistent with immunophenotype of MALToma. The
      serum immunoelectrophoresis demonstrated IgM (lambda) monoclonal gammopathy. The
      association of cold-reacting auto-antibody-mediated hemolytic anemia with
      MALToma, to our knowledge, has never been reported before in the English
      language.

PMID- 8275751
TI  - Transient swelling of the costochondral and sternal region in infants.
AB  - Four children aged 9 months, 11 months, 1 year, and 1 year 4 months,
      respectively, presented to the emergency room with an acute tender swelling of
      the sternum or sternocostal cartilage. Three of these resolved spontaneously
      within a few weeks of presentation, and in one curettage was carried out. We were
      unable to find any other references in the literature of this condition occurring
      in infants. Acute swelling of the chest wall frequently is due to neoplastic or
      infectious disease, and culture of aspirated material and possibly biopsy has
      been recommended in all cases. Our experience suggests that this may not always
      be necessary.

PMID- 8275752
TI  - Double outlet right ventricle associated with cor triatriatum sinistrum.
AB  - Echocardiographic examination of a newborn infant showed a double outlet right
      ventricle with subpulmonary ventricular septal defect. The left atrium was
      divided by a membrane-like structure into a proximal chamber receiving pulmonary
      veins and a distal compartment containing left atrial appendage. To our
      knowledge, this is the first report of cor triatriatum sinistrum associated with
      double outlet right ventricle.

PMID- 8275753
TI  - Two cases of scimitar variant.
AB  - The scimitar sign is characteristic of partial anomalous pulmonary venous
      drainage into the inferior vena cava (IVC). We encountered two variant cases of
      scimitar sign. In one case, the scimitar vein entered both the IVC and the left
      atrium (LA) without any intracardiac shunts. Surgical repair was made by simple
      ligation of the scimitar vein to correct the left to right shunt. Retrograde
      balloon occlusion angiography of the scimitar vein was diagnostic. In the other
      case, the scimitar vein showed a meandering course, and then drained into the LA
      without any connection with the IVC, and surgical intervention was not required.

PMID- 8275754
TI  - Scimitar sign with normal pulmonary venous drainage and systemic arterial supply.
      Scimitar syndrome or bronchopulmonary sequestration?
AB  - The classic definition of the scimitar syndrome is a triad of hypoplasia of the
      right lung with anomalous venous drainage and a systemic arterial supply of a
      variable degree. We report a case in which a scimitar-shaped anomalous vein was
      observed on the plain chest radiograph, but subsequently a pulmonary angiogram
      showed that it drained normally into the left atrium.

PMID- 8275755
TI  - Diffuse alveolar hemorrhage due to antibasement membrane antibody disease
      appearing with a polyglandular autoimmune syndrome.
AB  - We describe a patient with type 3-C polyglandular autoimmune syndrome who
      presented with diffuse alveolar hemorrhage and normal renal function. The
      diagnosis of antibasement membrane antibody disease was established by
      immunofluorescent staining of transbronchial biopsy specimens. We suggest the
      incorporation of antibasement membrane antibody disease into the spectrum of
      diseases that define the polyglandular autoimmune syndromes.

PMID- 8275756
TI  - Acute reversible cardiomyopathy associated with the systemic inflammatory
      response syndrome.
AB  - In the absence of ischemic heart disease, severe acute reversible myocardial
      dysfunction is uncommon, with sepsis most often being implicated in the ICU. We
      report a 38-year-old woman who developed profound transient myocardial depression
      due to nonseptic systemic inflammatory response syndrome caused by a necrotic
      kidney. Hemodynamic parameters and echocardiographic findings improved
      dramatically following nephrectomy. Other causes of acute myocardial suppression,
      including electrolyte abnormalities, drugs, catecholamine excess, and endocrine
      disease were excluded.

PMID- 8275757
TI  - The ECG in acute myocardial infarction.

PMID- 8275758
TI  - Multiple pulmonary chondromata. A rare cause of neonatal respiratory distress.
AB  - A neonate with respiratory distress due to a right pneumothorax is presented.
      After drainage of the pneumothorax, atelectasis of the entire right lung
      developed. Because the atelectasis persisted, bronchoscopy was performed. On
      bronchoscopy the carina and right main-stem bronchus could not be visualized.
      Thoracotomy showed that the right main-stem bronchus was obstructed by a space
      occupying lesion that was originating from the right upper lobe. Therefore, a
      sleeve resection of the right upper lobe was performed, and the right main-stem
      bronchus was reconstructed. Microscopic examination of the resected right upper
      lobe showed multiple chondromata. The lesions were located both in the lung
      parenchyma immediately beneath the pleura and in the bronchial wall. Pulmonary
      chondromata are rarely diagnosed in children. To our knowledge, this is the
      youngest patient ever presented with pulmonary chondromata.

PMID- 8275759
TI  - Sarcoid cardiomyopathy precipitated by pregnancy with cocaine complications.
AB  - We report the case of a 27-year-old previously healthy multiparous black woman
      who developed congestive heart failure 5 days postpartum. It was initially
      diagnosed and treated as idiopathic peripartum cardiomyopathy. Five weeks later,
      pulmonary sarcoidosis was diagnosed by transbronchial biopsy specimen, and
      steroid therapy was begun. An endomyocardial biopsy specimen 1 month later
      indicated cardiac sarcoidosis. She responded well to steroid therapy; however, 16
      months later, she had a cardiac arrest and died. Autopsy confirmed the diagnosis
      of cardiac sarcoidosis.

PMID- 8275760
TI  - Amiodarone-associated hemoptysis.
AB  - The manifestations of amiodarone pulmonary toxicity (APT) are generally
      nonspecific, and a diagnosis requires appropriate clinical history, laboratory
      testing consistent with toxicity, and exclusion of other disease entities. To our
      knowledge, hemoptysis associated with APT has not been described before; the
      following report describes such a case. We suggest that APT should be considered
      among the differential diagnosis of hemoptysis in a patient receiving amiodarone.

PMID- 8275761
TI  - Successful pregnancy after curative therapy for advanced lung cancer.
AB  - We report a single case in which two successful pregnancies occurred in a young
      woman following curative management of an advanced adenocarcinoma of the lung
      with resectional surgery and high-dose postoperative radiotherapy. This is the
      first case of advanced lung cancer with a favorable outcome.

PMID- 8275762
TI  - Bronchorrhea from diffuse lymphangitic metastasis of colon carcinoma to the lung.
AB  - Bronchorrhea, defined as watery sputum of 100 ml or more per day, was seen in a
      52-year-old female patient with diffuse lymphangitic metastasis of colon
      carcinoma to the lung. For 5 months before the visit to our clinic, she
      complained of progressive worsening of the cough, watery sputum, and shortness of
      breath. On admission to our hospital, she expectorated large amounts of
      nonpurulent watery sputum (150 to 300 ml/d), and showed diffuse reticular and
      linear shadows in both lungs on chest radiograph and severe obstructive
      impairment (FEV1 percent, 35 percent) in lung function tests. Histologic findings
      obtained from both surgical specimens at abdominal operation for ileus and lungs
      at the autopsy revealed lymphangitic metastasis of ascending colon carcinoma to
      the lung. At autopsy, histologically the lungs showed diffuse infiltrations of
      mucus-secreting adenocarcinoma cells to both lung parenchyma and airway
      submucosa.

PMID- 8275763
TI  - Lung transplantation for chemotherapy-induced pulmonary fibrosis.
AB  - A 26-year-old man cured of childhood acute lymphoblastic leukemia underwent a
      single lung transplant for drug-induced pulmonary toxicity 9 years after the
      completion of chemotherapy. It is not known whether patients cured of a
      malignancy who undergo organ transplantation are at increased risk of malignancy
      as compared to other organ transplant recipients. There was no evidence of
      recurrent or secondary malignancy in this case. Since single lung transplantation
      has been effective for idiopathic pulmonary fibrosis, it should be considered for
      patients cured of a malignancy who develop chemotherapy-induced pulmonary
      fibrosis.

PMID- 8275764
TI  - Lethal pulmonary embolism in a patient with primary antiphospholipid syndrome and
      a vena caval filter.
AB  - A 61-year old Hispanic woman with a history of primary antiphospholipid syndrome
      with pulmonary emboli and who was status post a vena caval filter placement to
      prevent recurrent pulmonary emboli, presented with acute onset of right upper
      quadrant abdominal pain. Acute cholecystitis was diagnosed and she underwent a
      surgically uncomplicated cholecystectomy. The postoperative course was
      complicated by new, massive pulmonary emboli despite prophylactic treatment with
      aspirin and low-dose heparin. Patient died en route to surgery for emergency
      embolectomy. This case suggests that a regimen of low-dose heparin and aspirin
      therapy in patients with primary antiphospholipid syndrome and a previously
      placed vena caval filter is not effective in preventing postoperative
      thromboembolic complications; more aggressive anticoagulation therapy is
      required.

PMID- 8275765
TI  - Talc pleurodesis during videothoracoscopy for Pneumocystis carinii pneumonia
      related pneumothorax. A new technique.
AB  - Pneumocystis carinii pneumonia in AIDS patients represents a growing problem for
      chest physicians. For thoracic surgeons, spontaneous pneumothorax and recurrent
      or persistent pneumothoraces can complicate this disease, requiring surgical
      intervention. Minimally invasive videothoracoscopy has now become a standard form
      of surgery for these patients, and we present a technique of talc insufflation
      that we believe is safe, simple, cost-effective, and reliable.

PMID- 8275766
TI  - Doppler analysis of pulmonary venous flow in left atrial myxoma.
AB  - In a patient with obstructive left atrial myxoma, we analyzed by pulsed Doppler
      echocardiography the flow pattern through the mitral valve and in the pulmonary
      veins. Two mitral flow patterns were observed: the first was present near the
      medial commissure and along the anterior leaflet and was characterized by the
      absence of mid-to-late diastolic filling flow; the second was found near the
      lateral commissure and was characterized by the obstruction of mid-to-late
      diastolic filling flow, mimicking mitral stenosis. The pulmonary vein flow showed
      brief and rapidly decelerating anterograde diastolic flow wave and an early
      systolic retrograde flow wave. These waves were respectively related to the
      diastolic forward and the systolic backward movement of the tumor. This case
      report shows that pulmonary vein flow analysis may give new insights into left
      atrial filling and emptying dynamics in left atrial myxoma.

PMID- 8275767
TI  - Role of Candida albicans in chronic hypersensitivity pneumonitis.
AB  - An autopsy was performed on a patient who had chronic hypersensitivity
      pneumonitis that was observed for 9 years. The patient was a farmer who developed
      symptoms every March through July during the use of moist hay that was infected
      heavily with Candida. Precipitins and an inhalation challenge test to C albicans
      were positive. We interpret the role of C albicans in this case.

PMID- 8275768
TI  - Endoscopic classification of tracheobronchial tuberculosis with healing
      processes.
AB  - We established an endoscopic classification of tracheobronchial tuberculosis with
      healing processes. According to this classification, the period of time needed
      for healing was found to be shorter in patients who were treated by aerosolized
      streptomycin than in those treated with the conventional triple-drug oral
      regimen.

PMID- 8275769
TI  - Allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.
AB  - In order to determine the incidence of allergic bronchopulmonary aspergillosis
      (ABPA) in patients with cystic fibrosis (CF), we reviewed the records of 236
      patients followed up at the Duke CF Center. Sixty patients (25 percent) had
      colonies of Aspergillus fumigatus. These patients were older and had more severe
      disease as assessed by lower Shwachman-Kulczycki (S-K) scores than the patients
      who did not have evidence of A fumigatus. In 15 of the patients with A fumigatus
      (6.5 percent of the total population), the diagnosis was ABPA. Age and S-K scores
      were not significantly different from those of the patients with A fumigatus
      without ABPA. Diagnostic features of the affected patients included wheezing
      refractory to bronchodilator therapy, persistent pulmonary infiltrates,
      peripheral eosinophilia, positive skin reactivity to an A fumigatus antigen and
      elevated total serum IgE levels. Steroid therapy was started for all patients,
      and clinical improvement was noted within 1 month as evidenced by decreased
      symptoms and weight gain. Chest x-ray films usually showed improvement. Vital
      capacity improved in all but two patients. Total IgE did not consistently
      decrease in response to therapy. Although the diagnosis of ABPA may be difficult
      to establish, ABPA commonly is associated with CF. Most patients respond to
      steroid therapy; however, the effect of therapy on the course of the disease is
      difficult to assess.

PMID- 8275770
TI  - Obstructive sleep apnea syndrome.

PMID- 8275771
TI  - Subcutaneous emphysema: spontaneous or iatrogenic?

PMID- 8275772
TI  - Role of closed-needle biopsy in the diagnosis of malignant mesothelioma of the
      pleura.

PMID- 8275773
TI  - Discordance between cardiopulmonary physiology and physical therapy.

PMID- 8275774
TI  - Mycobacterium kansasii infection following primary pulmonary malignancy.

PMID- 8275775
TI  - The wonderful floating features in medical imaging of chronic aspirated motor oil
      in the lung.

PMID- 8275776
TI  - Public health and tuberculosis.

PMID- 8275777
TI  - Lung transplants in patients with prior bone marrow transplants.

PMID- 8275778
TI  - Oral anticoagulant therapy recommendations.

PMID- 8275779
TI  - Pulmonary aspergillosis in patients with AIDS. Clinical and radiographic
      correlations.
AB  - OBJECTIVE: To evaluate the clinical and radiographic features of pulmonary
      aspergillosis as they present in AIDS patients; in particular, to determine
      similarities and differences between Aspergillus infection in patients with AIDS
      vs those without AIDS. SUBJECTS AND METHODS: Six new cases of confirmed or
      probable pulmonary aspergillosis were discovered during a search of hospital
      records. These are reviewed with 30 previously reported cases with special
      attention to radiographic appearance of disease and how radiographic appearance
      influences clinical outcome. RESULTS: Symptoms of pulmonary aspergillosis in AIDS
      were nonspecific, most often including fever, cough, and dyspnea, and less
      commonly, chest pain or hemoptysis. Major risk factors for the development of
      pulmonary aspergillosis in patients with AIDS were steroid administration and
      neutropenia. Neutropenia was often a complication of therapies for AIDS, in
      particular, ganciclovir and zidovudine. Radiographic appearance of disease could
      be divided into three general categories. One third of the patients (13/36)
      presented with cavitary upper lobe disease resembling noninvasive or chronic
      necrotizing aspergillosis. Fatal hemoptysis occurred in 42 percent of patients
      with this form of disease. Twenty-two percent (8/36) of the cases presented as a
      nondescript focal alveolar opacity similar to invasive aspergillosis. In several
      patients, the focal infiltrate remained stable for several months, a feature that
      is unusual for aspergillosis in non-AIDS patients. The air crescent sign was
      present in none of the 36 reported cases. Patients with only focal disease had
      the best prognosis of patients with pulmonary aspergillosis. Bilateral alveolar
      or interstitial disease similar to invasive aspergillosis was present in 23
      percent (9/36) of the patients. Bilateral disease appears to be a marker for
      disseminated infection and was associated with a high mortality due to
      aspergillosis. Two new forms of bronchial aspergillosis (5/36 cases) have been
      described previously. These patients presented with either obstructing fungal
      casts or bronchial pseudomembranes demonstrated bronchoscopically. In some
      patients with the bronchial forms of aspergillosis, transient alveolar opacities
      were seen on chest radiographs. These opacities may represent regions of
      atelectasis due to airway obstruction. One patient who had bilateral
      pneumothoraces without parenchymal opacities did not correspond to any of the
      three previously mentioned categories. Mortality due to aspergillosis was greater
      than 50 percent among AIDS patients. Death was subsequent to fatal hemoptysis or
      widespread pulmonary or systemic infection. CONCLUSION: Unlike other risk groups
      that tend to contract only one form of pulmonary aspergillosis, AIDS patients can
      develop the whole spectrum of aspergillosis-related pulmonary disorders,
      including chronic cavitary, invasive, and bronchial forms of aspergillosis.
      Clinical symptoms are nonspecific and major risk factors include neutropenia,
      which is often a side effect of various therapies for AIDS, and steroid
      administration. Patients with the chronic cavitary form of disease have an
      unusually high mortality due to fatal hemoptysis. Patients with bilateral
      pulmonary infiltrates and aspergillosis have a high mortality due to disseminated
      infection.

PMID- 8275780
TI  - High-technology home care. The need for a creative management approach.

PMID- 8275781
TI  - The third epidemic--multidrug-resistant tuberculosis.
AB  - We recently observed a striking increase in multidrug-resistant tuberculosis (MDR
      TB) among patients admitted to the Chest Service at Bellevue Hospital Center in
      New York. We reviewed the laboratory susceptibility test results of 4,681
      tuberculosis (TB) cases over the past 20 years, Combined resistance to isoniazid
      and rifampin increased from 2.5 percent in 1971 to 16 percent in 1991 with higher
      rates noted for individual drugs. We reviewed the medical records of 100 patients
      with drug-resistant TB, finding that these individuals were predominantly less
      than 40 years of age, minority, male, jobless, undomiciled, with a high
      percentage of drug abuse and human immunodeficiency virus infection. We conclude
      that the epidemics of AIDS and TB are complicated by a third epidemic of MDR-TB.
      This third epidemic requires urgent attention to achieve more rapid diagnosis, to
      develop new therapeutic regimens, and to address the social and hospital
      environment ot care for these individuals.

PMID- 8275782
TI  - Computed tomographic diagnosis of Mycobacterium avium-intracellulare complex in
      patients with bronchiectasis.
AB  - We tested the hypothesis that bronchiectasis and multiple small lung nodules seen
      on chest computed tomography (CT) are indicative of Mycobacterium avium
      intracellulare complex (MAC) infection or colonization by reviewing CT scans and
      histories of 100 outpatients with CT diagnosis of bronchiectasis. Of the 24
      patients with multiple pulmonary nodules, 19 had lung nodules and bronchiectasis
      in the same lobe. Mycobacterial cultures were performed on 63 of the 100
      patients, including 15 of the 24 patients with lung nodules and 48 of the 76
      patients with no lung nodules. Of the 15 patients with lung nodules, 8 (53
      percent) had cultures positive for MAC, as did 2 of the 48 (4 percent) patients
      with no CT evidence of lung nodules. The number of cultures positive for fungi
      was approximately the same in both groups. In our outpatient population, CT
      prediction of cultures positive for MAC in bronchiectatic patients with multiple
      small lung nodules has a sensitivity of 80 percent, a specificity of 87 percent,
      and an accuracy of 86 percent.

PMID- 8275783
TI  - Lobar pentamidine levels and Pneumocystis carinii pneumonia following aerosolized
      pentamidine.
AB  - Recent studies have suggested that failure of pentamidine prophylaxis against
      Pneumocystis carinii pneumonia (PCP) may be due to reduced deposition of
      pentamidine in the upper lobes. In this study, we performed bronchoalveolar
      lavage from the apical segment of the upper lobe and the middle lobe in 51 HIV
      positive patients, all of whom were receiving prophylaxis with aerosolized
      pentamidine, who had presented with acute respiratory symptoms. Lavage fluid from
      each lobe was assayed for pentamidine using high-performance liquid
      chromatography (HPLC). The number of clusters of P carinii were counted after
      staining with a Wright-Giemsa stain. The patients were subclassified as PCP
      positive (32 patients) and PCP-negative (19 patients) on the basis of the
      presence/absence of P carinii clusters in their BAL fluid. The concentration of
      pentamidine in the upper lobe compared with the middle lobe was no different
      (using paired Student's t tests) for either PCP-positive patients or PCP-negative
      patients. In comparing the positive with the negative subjects, using unpaired
      Student's t test, there was no difference in the concentration of pentamidine in
      the upper lobe or the middle lobe. For PCP-positive patients, the numbers of P
      carinii clusters were on average higher in the upper lobes (mean +/- SD: upper =
      14.9 +/- 16.6, middle 7.5 +/- 10.8, p = 0.013, paired Student's t test), but
      there was no correlation between lobar P carinii cluster counts and pentamidine
      levels. We conclude that the absence of a relationship between cluster count and
      pentamidine level, the similarity in regional pentamidine levels between upper
      and middle lobes, as well as the similarity in pentamidine levels between the PCP
      positive and PCP-negative groups indicate that the regional dose of pentamidine
      is not the determining factor as to whether aerosolized pentamidine prophylaxis
      will succeed or fail.

PMID- 8275784
TI  - Cardioprotective effect of unstable angina prior to acute anterior myocardial
      infarction.
AB  - To evaluate the difference in the process of left ventricular functional recovery
      after successful percutaneous transluminal coronary angioplasty (PTCA), 25
      patients with sudden onset of acute Q wave anterior myocardial infarction (MI
      [group 1]) and 28 patients with unstable angina prior to MI (group 2) were
      investigated in the late hospital phase. The circumferential extent of left
      ventricular dysfunction was significantly larger in group 1 than in group 2. The
      left ventricular ejection fraction (EF) and the ratio of systemic arterial
      systolic blood pressure to left ventricular end-systolic volume (P/V ratio) were
      significantly lower in group 1 compared with group 2. The P/V ratio had nonlinear
      relationships with left ventricular end-diastolic volume (LVEDV) in both groups
      and the P/V ratio in group 1 was significantly lower than those in group 2 at any
      given LVEDV. Thus, in patients with successful PTCA, unstable angina prior to
      acute MI had better left ventricular pump function in the course of left
      ventricular remodeling.

PMID- 8275785
TI  - Mycobacterium avium complex lung disease and women. Now an equal opportunity
      disease.

PMID- 8275786
TI  - Amrinone: its effect on vascular resistance and capacitance in human subjects.
AB  - Reports evaluating amrinone's effects in normal (intact) human subjects are
      complex and difficult to interpret because of the drug's diverse effects on
      myocardial function, resistance vessels, and vascular capacitance. In this study,
      1.5 mg/kg of amrinone was administered as an intravenous bolus to cardiac
      surgical patients during constant flow cardiopulmonary bypass to determine its
      isolated effects on venous capacitance and vascular resistance. We noted a
      significant decrease in vascular resistance up to 8 min after injection and a 460
      +/- 160 ml (mean +/- SD) decrease in venous reservoir volume 10 min after
      injection. Amrinone has potent venous and arterial vasodilating properties that
      make it a unique drug for treating congestive heart failure in addition to its
      reported positive inotropic effects.

PMID- 8275787
TI  - Familial cardiac myxoma. A study of relatives of patients with myxoma.
AB  - PURPOSE: Cardiac myxomas are rare benign tumors of the heart. Although most cases
      are sporadic, rare familial occurrence has been described. The aim of this study
      was to evaluate tumor involvement in family members of patients with cardiac
      myxoma and to compare familial vs nonfamilial cardiac myxoma in relation to age,
      sex, site and multichamber involvement, endocrine abnormality, embolism, presence
      of vascular aneurysms, and tumor recurrence. PATIENTS AND METHODS: We studied 38
      family members of 14 patients with cardiac myxoma by two-dimensional
      echocardiography and whenever possible on an annual basis. Patients with cardiac
      myxoma were then divided into familial cardiac myxoma (6 patients) and
      nonfamilial cardiac myxoma (12 patients) for the above comparison. RESULTS: Four
      family members (10.5 percent) were found to have cardiac myxoma from two
      different families. The first included a brother and a sister, both with
      acromegaly, and the second included a mother, daughter, and two sons, in one of
      whom the tumor was detected on the second annual sons, in two-dimensional study.
      The patients with familial cardiac myxoma were younger (34.8 years vs 54 years, p
      < 0.001) than the nonfamilial cases. Right chamber involvement was more common in
      the familial cases (67 percent vs 8 percent, p < 0.05) and had more frequent
      recurrence (67 percent vs none, p < .05). There was no difference in endocrine
      abnormality, vascular aneurysms, or embolism between familial and nonfamilial
      cases. CONCLUSION: Cardiac myxoma is relatively frequent in family members with a
      higher yield of detection in family members of patients with right-sided or
      bilateral myxoma. Patients with familial cardiac myxoma are younger and have more
      frequent right-side involvement and long-term recurrence. Screening by
      echocardiography of family members of patients with cardiac myxoma is
      recommended. Annual studies are recommended for relatives of patients with
      familial cardiac myxoma.

PMID- 8275788
TI  - Reliability of the radial arterial pressure during anesthesia. Is wrist
      compression a possible diagnostic test?
AB  - STUDY OBJECTIVE: To evaluate wrist compression as a test to identify low radial
      from low systemic pressure and to see if the gradient found after cardiopulmonary
      bypass is also present whenever hand vascular resistance may decrease. DESIGN:
      This was a prospective study. SETTING: Operating room area of a university
      medical center. PARTICIPANTS: (1) Forty patients undergoing coronary bypass
      grafting studied at discontinuation of cardiopulmonary bypass. (2) Twenty-six
      patients received isoflurane anesthesia before major noncardiac operations. (3)
      Hydraulic model: a fluid container with a tube 66-cm long, 6- to 1.8-mm internal
      diameter, connected at its base. INTERVENTIONS: Before induction of anesthesia,
      the radial artery was cannulated and, in the first group, the aorta or femoral
      arteries as well. The radial pressure was compared consecutively with and without
      wrist compression. In the model, the pressure was recorded simultaneously at
      three sites along the tube while different flows ran through its distal end.
      MEASUREMENTS AND RESULTS: Overall, wrist compression increased radial (p < 0.001)
      systolic, diastolic, and mean arterial pressures. In the first group, compression
      reduced the femoral/aortic-radial mean pressure difference by 50 percent and
      never produced higher radial than central mean pressure. Plot of the pressure
      difference produced by wrist compression against the average of the (compared)
      radial pressures and considering increases > or = 4 mm Hg as real, showed that,
      in the first group, systolic arterial pressure (SAP) increased 13 +/- 1.4 mm Hg
      in 22 of 40 patients; diastolic arterial pressure (DAP) increased 7.8 +/- 1.1 mm
      Hg in 4; and mean arterial pressure (MAP) increased 7.7 +/- 1.6 mm Hg in 9
      patients. In the second group, SAP increased 16.0 +/- 1.7 mm Hg in 24 of 26
      patients, DAP increased 6.0 +/- 1.4 mm Hg in 5, and MAP increased 7.0 +/- 0.7 mm
      Hg in 18 of 26 patients. In the model, base pressure at 94 mm Hg, the pressures
      were 1.2 to 28.1 mm Hg lower for flows ranging from 10 to 122 ml/min at the 54-cm
      distance (wrist equivalent). CONCLUSION: The systemic-radial artery pressure
      gradient seen at the end of cardiopulmonary bypass seems to be a phenomenon
      common to patients with decreased hand vascular resistance. Wrist compression
      decreases or abolishes the gradient in most cases. It does not produce false
      positives, so an increase indicates a greater aortic than radial pressure. The
      difference is likely to be only temporary.

PMID- 8275789
TI  - A new look at dopamine and norepinephrine for hyperdynamic septic shock.

PMID- 8275791
TI  - Plaques, cancer, and confusion.

PMID- 8275790
TI  - Early sepsis treatment with immunoglobulins after cardiac surgery in score
      identified high-risk patients.
AB  - In patients at risk for sepsis after cardiac surgery, the efficacy of intravenous
      immunoglobulin (Ig) treatment was compared with a historical control population,
      equivalent in patient characteristics and disease severity. Using APACHE II
      scores, especially in the high-risk group (IgG), we could discriminate between
      low-risk patients (score < 19; mortality 1 percent) and the small groups at risk
      (score 19 to 23) and high risk (score > or = 24) with a significantly higher
      mortality (14 percent and 76 percent, respectively) [corrected]. Subsequently,
      among 1,341 consecutive patients we prospectively identified and treated (IgG n =
      41 IgGMA: n = 25) these at-risk groups. In contrast to controls (risk: n = 21;
      high-risk; n = 21), we found a marked fall in APACHE II scores, especially in the
      high-risk group (IgG, n = 26: p < 0.05; IgGMA, n = 13: p = 0.08) [corrected]. In
      this group, Ig therapy produced higher (p < 0.05) response rates (score decrease
      7 within 4 days: IgG: 54 percent, IgGMA: 62 percent; controls: 19 percent) and
      reduced mortality (IgG: 46 percent, IgGMA: 46 percent; controls: 76 percent),
      statistically significant (p < 0.05) for Ig treatment overall. Thus, early Ig
      treatment improves disease severity and may improve prognosis in prospectively
      score-identified high-risk postcardiac surgical patients.

PMID- 8275792
TI  - Comparison of cardiac pacing modes in patients with chronic obstructive pulmonary
      disease.
AB  - STUDY OBJECTIVE: This study compares the relative benefits of dual chamber
      adaptive rate pacing (DDDR) with ventricular adaptive rate pacing (VVIR) in
      patients with chronic obstructive pulmonary disease (COPD). STUDY DESIGN: Cardiac
      hemodynamics were evaluated with serial exercise tests. A minimum of 2 h was
      allowed between studies. Pulmonary gas exchange was measured and cardiac output
      (CO) was determined at rest and immediately after maximum exercise by Doppler
      echocardiography. PATIENTS: Sixteen patients with DDDR pacemakers were studied.
      Eight patients had COPD and eight patients had normal lung function (NLF).
      Baseline lung function was documented with spirometry. INTERVENTIONS: The
      patients with NLF functioned as a control group. Prior to entry into the study,
      the rate-modulated parameters of the pacemaker were programmed to a clinically
      determined optimal set of parameters for each individual patient. These were not
      changed for the duration of the study. RESULTS: Both groups showed a
      statistically significant improvement in exercise duration, CO at maximum
      exercise, and cardiac output difference (CODiff) with the dual chamber adaptive
      rate pacing mode (DDDR). (COdiff is the change in CO from rest to maximum
      exercise.) Patients with NLF also showed a significant improvement in anaerobic
      threshold (AT) and VCO2 max with DDDR. Patients with lung disease showed a
      statistically significant improvement at all levels of exercise in the
      ventilatory equivalent for oxygen. CONCLUSION: In this study, those patients with
      chronic lung disease who required cardiac pacing performed significantly better
      in the DDDR mode as compared with the VVIR mode. Therefore, the DDDR pacing mode
      should provide an improved quality of life for the patient with COPD who also
      requires cardiac pacing.

PMID- 8275793
TI  - Four-week negative pressure ventilation improves respiratory function in severe
      hypercapnic COPD patients.
AB  - Studies on respiratory muscle resting by negative pressure ventilation (NPV) in
      patients with stable COPD have given conflicting results. Probable explanations
      lie in criteria of patients' selection, method of NPV application, and lack of
      supervision of respiratory muscle rest. Thirteen hypercapnic patients with COPD
      were, therefore, randomly assigned to either a NPV group or a control group. The
      NPV was applied by an airtight jacket (pneumosuit), 5 h a day, 5 consecutive days
      a week for 4 weeks. Both NPV group and control group performed in-hospital
      pulmonary rehabilitation program for a 4-week period. Arterial blood gases,
      spirometry, maximal inspiratory pressure (MIP) and maximal expiratory pressure
      (MEP), breathing pattern, and electromyogram (EMG) of the diaphragm and
      parasternal intercostal muscles were measured on the preintervention day, and at
      the end of the second and fourth weeks of treatment (days 13 and 27,
      respectively). The short-term effect of NPV on EMG suppression was also checked
      throughout the ventilatory sessions in three different days (1, 12, and 26,
      respectively). A 6-min walking test (WT) and level of dyspnea by a modified Borg
      scale were evaluated on the preintervention and the last days. Negative pressure
      ventilation resulted in a significant reduction in EMG activity of both diaphragm
      and parasternal muscles, associated with significant increase in MIP, tidal
      volume, and ventilation, and increase in PaO2 and decrease in PaCO2. A
      significant relationship between change in MIP and change in PaCO2 was observed
      (r = 0.72, p < 0.01). Improve-ment in 6-min WT and dyspnea sensation was also
      observed, both being the sole changes in the control group. These data seem to
      indicate a beneficial role of respiratory muscle rest in improving respiratory
      function. Adequate supervision by personnel familiar with the equipment is likely
      to contribute to successful treatment.

PMID- 8275794
TI  - The effect of intermittent negative pressure ventilation and long-term oxygen
      therapy for patients with COPD. A 4-year study.
AB  - We evaluated retrospectively the effect of long-term oxygen therapy (LTOT) on the
      prognosis of 35 patients with chronic obstructive pulmonary disease (COPD) and
      chronic respiratory insufficiency (group A) who were admitted to our respiratory
      intensive care unit from 1984 to 1986 for acute respiratory failure (ARF). All
      subjects were given intermittent negative pressure ventilation (INPV) by means of
      an iron lung to overcome the acute episode and were treated with LTOT after
      discharge. Forty-four patients with COPD who were treated with the same
      ventilatory method to overcome an acute disease exacerbation and who were not
      given LTOT were used as controls (group B). Both groups were followed up for at
      least 48 months. All relapses of ARF were treated by iron lung in both groups A
      and B. The overall survival was significantly better in group A than in group B
      (p = 0.05 by F test) indicating that LTOT improves survival in patients with COPD
      after a bout of ARF treated with mechanical ventilation. Therefore, combining
      INPV with LTOT for overcoming acute episodes and relapses of ARF appears to
      improve the prognosis of patients with COPD.

PMID- 8275795
TI  - Epinephrine stimulates Na-K pump by mediation of alpha-and beta-adrenoceptors in
      canine cardiac Purkinje fibers.
AB  - The effects of epinephrine on the twitch tension, intracellular Na+ activity
      (aiNa), and action potential were simultaneously investigated in an electrically
      driven canine Purkinje fiber. Epinephrine (0.3 microM) increased the twitch
      tension, duration of action potential (APD), and plateau height with a fall in
      aiNa. The twitch force increased during exposure and decreased during recovery.
      Propranolol (3 microM) or lidocaine (10 microM) decreased the twitch tension,
      APD, and aiNa when added to the bathing solution alone. They partially inhibited
      the effects of epinephrine (0.3 microM) on the development of the twitch tension
      and action potential and on the decrease of aiNa. Phentolamine (2 microM) reduced
      the twitch tension and plateau height of the action potential but failed to
      eliminate the action of epinephrine on the fibers. The combined action of
      phentolamine and epinephrine abbreviated the APD. The effect of epinephrine on
      the decrease of aiNa was entirely suppressed when the fiber was pretreated with
      propranolol (1 microM) and phentolamine (1 microM) or in a potassium-depleted
      solution. The results indicate that epinephrine exerts effects on the canine
      Purkinje fiber by the mediation of alpha-and beta-adrenoceptors. Adrenoceptor
      stimulation of both types is involved in the positive inotropic effect and the
      activation of the sarcolemmal Na-K pump.

PMID- 8275796
TI  - Sensitivity to dopamine blocking in rat licking behavior: function of taste
      stimuli, response difficulty, and response measures.
AB  - The behavioral circumstances determining the efficacy of DA blocking was studied
      by observing the effects of pimozide, tastes and effort required to ingest liquid
      on consummatory licking responses. The microstructure of ingestive behavior was
      obtained to delineate differential behavioral adjustments. Twelve water-deprived
      rats were trained to lick water, 2.00% sucrose, and 0.01% quinine from a spout
      located either at a down position of 7 cm above (low effort) or an up position of
      24 cm above the floor (high effort). They were injected with pimozide (0.25
      mg/kg, ip) or its vehicle and licking responses were observed. Results indicated
      that the pimozide effect was dependent on tastes and positions as well as the
      behavioral aspects observed. Pimozide affected ingestion of quinine in many ways,
      but did not affect that of sucrose solution. The position affected ingestion of
      quinine in more ways than that of sucrose solution. The taste effect of quinine
      was more complex than that of sucrose. The complex behavioral adjustment to the
      reduced incentive support with quinine probably rendered the behavior vulnerable
      to interference by DA blocking and effort requirement.

PMID- 8275797
TI  - Neurons in the pressor sites of dorsal and ventrolateral medulla mediate pressor
      actions of the periaqueductal grey of midbrain.
AB  - In 14 cats anesthetized with chloralose (40 mg/kg) and urethane (400 mg/kg) the
      pressor area in the ventrolateral periaqueductal grey (PAG) of midbrain was
      activated by rectangular pulses. The induced increases of systemic arterial
      pressure (SAP) and plasma norepinephrine (NE) and epinephrine (EPi) were compared
      before and after destructing portion of cell bodies (sparing passing fibers) in
      the pressor sites of dorsal (DM) and rostral ventrolateral medulla (VLM) by
      microinjection of kainic acid. Destruction on VLM or DM reduced the PAG-induced
      pressor responses and increases in plasma NE and EPi. The reduction of pressor
      responses, however, was more predominant following VLM than DM destruction. On
      the other hand, the decrease in plasma NE, was slightly more apparent following
      DM than VLM destruction.

PMID- 8275798
TI  - Platelet-activating factor receptor-mediated calcium influx in NG 108-15 cells.
AB  - Platelet-activating factor (PAF) elicited an increase in intracellular Ca2+
      concentration, [Ca2+]i, in neuroblastoma x glioma hybrid NG 108-15 cells as
      measured by fura-2 fluorescence method. The rise in [Ca2+]i was primarily due to
      the influx of Ca2+ from extracellular source. Preincubation of cells with the
      Ca(2+)-ion channel blockers, including verapamil, nifedipine and conotoxin, did
      not affect the Ca(2+)-response stimulated by PAF, indicating that the PAF
      elicited Ca(2+)-influx is not mediated through the classical voltage-dependent
      Ca(2+)-ion channels. In contrast, SK&F 96365, which is an inhibitor of receptor
      operated calcium channel, blocked the PAF-elicited Ca(2+)-response dose
      dependently. When cells were pretreated with the protein kinase C activator,
      phorbol 12-myristate 13-acetate (PMA), PAF-elicited Ca(2+)-signal was diminished
      substantially. In contrast, the protein kinase A activator, forskolin, has no
      effect on the Ca(2+)-response induced by PAF. Further experiment demonstrated
      that genistein, an inhibitor of tyrosine kinase, also caused inhibition on PAF
      induced Ca(2+)-response significantly. There results suggest that the PAF
      receptor-coupled Ca(2+)-ion channel is subjected to the modulation by protein
      kinase C and tyrosine-specific kinase. Pretreatment of cells with PAF resulted in
      the desensitization of the Ca(2+)-response following further stimulation with the
      same agonist. The heterologous desensitization of the PAF-induced Ca2+ influx was
      also observed in cells pretreated with bradykinin or to a less extent with ATP.
      Conversely, pretreatment of cells with PAF affected only partially the Ca(2+)
      response elicited by bradykinin or ATP. Additive response was observed when PAF
      and ATP were added together but not PAF and bradykinin.

PMID- 8275799
TI  - Effect of hypothyroidism on the in vitro release of atrial natriuretic peptide in
      response to sodium challenge in rats.
AB  - The release of atrial natriuretic peptide (ANP) in vitro in response to the
      challenge of sodium chloride was investigated in hypothyroid rats. Male rats were
      injected with propylthiouracil (PTU, 20mg/kg BW, intraperitoneally), or PTU and
      thyroxine (T4, 20 micrograms/kg BW, subcutaneously) once daily for 14 days before
      decapitation. Rats injected with saline were used as control. The plasma samples
      were collected and extracted by Sep-Pak C18 cartridge. The concentrations of ANP
      in extracted plasma were measured by a radioimmunoassay (RIA). PTU-induced
      hypothyroidism resulted in decreased concentrations of plasma ANP. Replacement of
      T4 in PTU-treated hypothyroid rats restored the plasma concentrations of ANP to
      normal levels. Furthermore, we examined the right atrial ANP contents and the in
      vitro release of ANP in PTU-treated rats and control animals. The right atrium
      was excised and divided into 5 equal pieces, one was homogenized with 0.1 N HCl
      and extracted by Sep-Pak C18 immediately, and the others were incubated with
      Locke's solution at 37 degrees C. After basal incubation for 30 min, rat atrial
      tissues were then incubated with 154, 160, or 165 mM NaCl for 30 min. The
      concentrations of ANP in extracted atrial tissue and medium samples were also
      measured by RIA. Decreased atrial contents of ANP were noted in hypothyroid rats.
      The in vitro release of ANP in response to 165 mM sodium ion was significantly
      lower in PTU than in saline-injected animals. These results suggest that lower
      concentration of plasma ANP in hypothyroid rats is at least in part due to
      impairment of stimulation-secretion responses of right atria during thyroid
      hypofunction in rats.

PMID- 8275800
TI  - Directional sensitivity of inferior collicular neurons of the big brown bat,
      Eptesicus fuscus, to sounds delivered from selected horizontal and vertical
      angles.
AB  - Under free field stimulation conditions, directional sensitivity of 336 inferior
      collicular (IC) neurons of 6 Eptesicus fuscus was studied by recording the
      minimum threshold (MT) and number of impulses of each neuron to a best frequency
      (BF) sound delivered from selected horizontal and vertical angles. An auditory
      response center was determined for each neuron by delivering a BF sound from a
      specific point of the bat's frontal auditory space. At the response center, the
      neuron had maximal directional sensitivity and lowest MT. Auditory response
      centers of all 336 IC neurons studied were located in the contralateral frontal
      auditory space and they shifted from lateral angles toward the midline with
      increasing BF. Sound direction affected the sharpness of frequency tuning (i.e.
      Q10-dB value) but not the BF and overall shape of the frequency threshold curve
      of a neuron. Sound direction also affected the MTs, number of impulses and
      intensity-rate functions but not the discharge patterns of IC neurons. High BF
      neurons generally had sharper directional sensitivity than low BF neurons.
      Bending downward the pinna contralateral to the recording site increased a
      neuron's MT and shifted its response center downward and toward the midline of
      the bat's frontal auditory space. The effect of pinna bending on a neuron's MT
      and impulse directional curves can be explained on the basis of variation of its
      auditory response area and its MT.

PMID- 8275801
TI  - [Salivary duct carcinoma (clinicopathologic study of 11 cases)].
AB  - Eleven cases of salivary duct carcinoma were studied clinicopathologically. The
      clinical features are as follows: men outnumber women; arise most frequently
      within the parotid glands; rapidly enlarging mass; obvious symptoms of invading
      nerves; high rates of cervical lymph node and distant metastases; poor patient's
      prognosis. Its histologic features were shown by the various stages of
      development of duct carcinoma including dysplasia, carcinoma in situ, papillary,
      cribriorm, solid and commedo patterns. In addition to the intraductal carcinoma,
      there is the invasive carcinoma with obvious infiltration into the surrounding
      tissues. Its treatment requires the combination of radical surgery with
      postoperative radiotherapy.

PMID- 8275802
TI  - [Maxillofacial tomography (MT tomography) in the diagnosis of diseases on the
      middle 1/3 of the face].
AB  - Maxillofacial tomography apparatus (MT tomography) is a panoramic tomographic
      unit, radiographing in recumbent position. Its image can show most of the
      anatomic structures of maxillofacial bones. Through comparative examination
      between the conventional roentgenograms (general radiographs, pantomographs and
      laminagrams) and MT tomography of 48 patients, it is found that MT tomography has
      certain advantages for the diagnosis of the range, extent and quality of
      fracture, tumour and tumour like disease in maxillofacial bones and that MT
      tomography can serve as an effective auxillary method of diagnosis for the
      conventional roentgenograms used for maxillofacial bones.

PMID- 8275803
TI  - [A quantitative study of the ranges of mandibular movement in normal subjects
      with the digital sirognathograph (D-SGG)].
AB  - This paper is to study the mandibular border movement showing in three different
      direction observations, mandibular tapping movement showing in two different
      direction observations and the mandibular movement of two types of foods by using
      D-SGG which is an accurate and convenient measurement system of mandibular
      movement tracks. The results are as follows: 1. a normal ranges of the mandibular
      border movement are made and the variations of the ranges are quite small in
      normal subjects, no significant difference is found. 2. the variations of mouth
      opening are greater in tapping movement than in border movement. The
      distributions of the tracks of tapping movement are about 4.0 mm, but the
      coefficient of variation is considerable. 3. The quality and quantity of test
      foods effect the ranges of mouth opening in chewing movement.

PMID- 8275804
TI  - [A comparative study on the nasolance and graph pattern of cleft palate patients
      before and after operation].
AB  - The aim of the present study is to compare the nasolance score and graphic
      pattern of the nasometric registration before and after cleft palate repair.
      Sixty cleft palate patients were studied with nasometer. One month after
      operation the nasolance is significantly lower as compared with the preoperation
      sequence and the number of "up and down" pattern has increased significantly.
      These results indicate that the velopharygeal function starts to recover one
      month after operation and the speech training can be given at the mean time. The
      speech results should be assessed at least three months after operation.

PMID- 8275805
TI  - [Familial cherubism (report of 10 cases)].
AB  - 10 cases of familial cherubism were presented. Of them, there were 7 patients
      under 9 years of age. Painless swelling of the mandible was exclusively
      complained. The lesions often occurred bilaterally (9/10), resulting in "square
      jaw" deformity. The radiographs usually revealed multicystic appearance with
      various opacities (8/10) and widen, sclerotic margins (7/10). Other common
      manifestations included impaction and absence of teeth (7 for each) and twisted
      roots (6/10). At follow up for 3 years and 5 months, the lesions in 2 cases
      without operation tended to be steady or unchanged radiographically. In 3 cases
      treated by enucleation, no recurrence was noted at follow-up for 1 year and 2
      months, 10 years and 9 months, and 15 years and 4 months after operation
      respectively.

PMID- 8275806
TI  - [Experimental study on the effect of unilateral mastication on the morphology of
      mandibular joint].

PMID- 8275807
TI  - [The measurement and the correlative and regressive analysis on the development
      of tooth hard tissue from human fetus].

PMID- 8275808
TI  - [Experimental study on the interaction of fibronectin with oral Streptococci].
AB  - Interaction of fibronectin (Fn) with Streptococcus mutans, S. sorbrinus, and S.
      milleri is demonstrated by an enzyme-linked immunosorbent assay (ELISA). The
      results show that the three strains are able to adhere to Fn. The interaction may
      be strengthened while the concentration of Fn increases (q test P < 0.01). The
      ability of adherence among S. mutans, S. sorbrinus and S. milleri is different in
      Fn high concentration (q test P < 0.01). It is speculated the free Fn in saliva
      may serve as an agglution for elimination of the organisms from the oral cavity,
      or as a receptor when immobilized on the tooth surface for cariogenic
      streptococci to form plaque. A balance between these two functions of Fn may play
      a role in modulating the microbial ecological environment of the oral cavity.

PMID- 8275809
TI  - [The effect of antibody to Streptococcus mutans in saliva on caries activity and
      S. mutans adhering].
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) was used for measuring IgA
      antibody to whole cell of Streptococcus mutans (serotype c) in saliva. 36 parotid
      salivary samples of human were collected from two groups: Caries free (CF) and
      caries sensitive (CS). The result shows that the IgA antibody to S. mutans in CF
      group was higher than those in CS group (P < 0.05). The saliva antibody was
      gained from the rabbits by injection with S. mutans (serotype c), and the
      adhesion of S. mutans--3H on the surface of hydroxylapatite beads treated by
      rabbit's saliva was measured. The results show that the saliva with immunity
      could inhibit the S. mutans to adhere on the HA beads (P < 0.05). It means saliva
      antibody may prevent caries through inhibition of S. mutans from adhesion.

PMID- 8275810
TI  - [Isolation and purification of the glucosyltransferases from Streptococcus
      mutans].

PMID- 8275811
TI  - [A study of skeletal types of class III malocclusion].
AB  - 300 class III cases of mixed dentition, early permanent dentition were
      discriminated quantitatively according to their SNA, SNB and SN-MP angles. Six
      quite different types were grouped: 1. Mandibular prognathism with normal
      maxilla. Most common type, in which about 40% are "high angle" or "low angle"
      cases, which show more severe class III skeletal face than normal SN-MP angle
      ones; 2. Maxillary retrognathism with normal mandible. More than 50% cases are
      with high SN-MP angle, which show less severe class III skeletal face than those
      with normal one; 3. Normal maxilla and mandible type, the "high" and "low" angle
      cases are fewer. The severity of class III skeletal face is slight; 4. Maxillary
      retrognathism and mandibular prognathism type, the class III skeletal face,
      especially for those with high SN-MP angle cases is most severe; 5. Bimaxillary
      prognathism type, it is the expression of racial feature of Chinese face and 6.
      Bimaxillary retrognathism.

PMID- 8275812
TI  - [Observation of morphology of microvessels in periodontal tissue before and after
      orthodontic treatment were compared using vessel casting technique with scanning
      electron microscopy].

PMID- 8275813
TI  - [Experimental study on the skeletal and periodontal alterations induced by rapid
      maxillary expansion].

PMID- 8275814
TI  - [Effect of class II elastics on the moving pattern of anterior teeth].

PMID- 8275815
TI  - [Current status of orofacial granuloma].

PMID- 8275817
TI  - [A new recognition of re-expansion pulmonary edema].

PMID- 8275816
TI  - [Occlusal factors in temporomandibular joint disorder syndrome].

PMID- 8275818
TI  - [The importance of etiologic diagnosis of infectious diseases].

PMID- 8275819
TI  - [The effect of low doses of recombinant human erythropoietin on renal anemia in
      predialysis patients with chronic renal failure].
AB  - Subcutaneous (s.c.) administration of recombinant human erythropoietin (rHuEPO)
      has been proven to be effective in anemia of predialysis patients with chronic
      renal failure (CRF). However, the optimal dosage and frequency of administration
      have not been established. We use low dose (< 100U.kg-1.w-1) of s.c. rHuEPO to
      treat renal anemia in two groups (group A: n = 18, twice a week; group B; n = 14,
      once a week) of nondialytic CRF patients. Hb and Hct gradually increased 1-3
      months aftes rHuEPO treatment in the two groups. The incidence of hypertension,
      one of the main side effects, was lower (4/18 in Group A, 4/14 in Group B) than
      that reported in the literature. These results showed that either twice weekly or
      once weekly s.c. injection of low dose rHuEPO is effective and there will be less
      side effects treating predialysis patients with CRF.

PMID- 8275820
TI  - [Histological classification of uremic bone disease and clinical significance of
      bone biopsy].
AB  - Bone biopsy was performed in 429 cases of uremic bone disease and they were
      classified histologically into 3 groups--high turnover 129 (30%), low turnover
      102 (24%) and mixed type 198 (46%) cases. The histological features of the high
      turnover type were increased corrected mineralization rate (CMR) and osteoclast
      member and decreased mineralization lay time (MLT), while those of the low
      turnover type were on the contrary. In the mixed there were decrease of CMR and
      increase of MLT and osteoclast number. Bone aluminum positive rate was
      determined; it was 75% and 80% respectively in the low turnover and mixed type
      and 29% in high turnover. Biochemical study showed that significantly higher
      levels of serum PTH and alkaline phosphate in the high turnover type and low
      levels of serum 1,25(OH)2D3 and 25(OH)D3 in the low turnover. These results
      suggested that high turnover uremic bone disease is caused by secondary
      hyperthyroidism and low turnover mainly related to aluminum toxicity or other
      causes such as vitamin D deficiency.

PMID- 8275821
TI  - [A pathological analysis of 51 cases of renal osteodystrophy].
AB  - Renal osteodystrophy is a metabolic bone disease of chronic renal failure. The
      long-standing alterations in mineral metabolism generated by renal failure have a
      profound effect on the skeleton and induce severe systemic metabolic bone
      disease. Iliac crest biopsy was performed in 51 patients of chronic renal failure
      and examined with microscopy. The histological bone changes are characterized by
      ostitis fibrosa, increased resorption of bone and number of osteoclasts,
      increased osteoid volume (osteoblastic osteoid and acellular osteoid), active
      remodelling of bone and aluminum deposition in bone. According to the
      histological appearance, advanced renal bone disease can be subdivided into three
      major histological groups: secondly hyperparathyroid bone disease (high turnover
      uremic osteodystrophy), osteomalacia (low turnover uremic osteodystrophy) and
      mixed uremic osteodystrophy consisting of mild to moderate hyperparathyroid bone
      disease and defective mineralization. Aluminum-related bone changes can be seen
      in varying degrees in all these groups. Even though these groups do not fully
      represent separate entities and transformation from one form to another can
      occur, it is essential to distinguish them since therapy can be tailored
      according to the predominant histologic findings.

PMID- 8275822
TI  - [Serum apolipoproteins in uremic patients].
AB  - Serum Apolipoproteins (Apo) and lipids were determined in 20 patients with
      uremia. The results were compared with those obtained in sex and age matched
      controls. The patients had significantly reduced level of Apo AI and ratio of Apo
      AI/Apo B100, and increased levels of Apo CII, Apo CIII. It was also found that
      the patients had normal levels of TC, TG and significant decrease of HDL-C, HDL2
      C. These findings suggested that Chinese uremic patients had wide extensive Apo
      abnormalities which could induce disturbances of lipid metabolism and development
      of atherosclerosis although serum lipid levels were normal, and that Apo might be
      better predicators of cardiovascular complications than lipids in Chinese
      patients with uremia.

PMID- 8275823
TI  - [A study of left ventricular function in normal persons and patients with old
      myocardial infarction with three dimensional echocardiography (3-DE)].
AB  - The accuracy of 3-DE in evaluating the volumes of left ventricule (LV) and volume
      changes in cardiac cycle was discussed. The LV volumes measured with 3-DE in
      porcine hearts is more closely to the real volumes directly measured (P > 0.05 r
      = 0.93). The EF value measured with radionuclide has higher correlation with that
      of 3-DE (r = 0.88) in patients. In a quantitative analysis of LV volume changes
      in cardiac cycles, we found that the decrease of EF in patients with old
      myocardial infarction (OMI) occurs mainly at the early stage and lasts to middle
      stage of systole in anterior myocardial infarction. Dysfunction of filling in OMI
      took place at the early and middle stages of diostole. Segmental shortening of LV
      was analysed quantitatively by percentage and pseudocolour mark. The reference
      values of 3DE in cardiac function were shown.

PMID- 8275824
TI  - [Evaluation of endoscopic retrograde cholangiopancreatography in diagnosis of
      chronic pancreatitis].
AB  - 155 cases of chronic pancreatitis in PUMC hospital from 1952 to 1990 were
      investigated. Because endoscopic retrograde cholangiopancreatography (ERCP) and
      exocrine pancreatic function tests have been used since 1974, the diagnostic rate
      of chronic pancreatitis during 1974-1990 is 6.6 fold as that during 1952-1974.
      The pancreatic duct in 97 cases among 105 cases with chronic pancreatitis
      examined by ERCP was compared with CT and ultrasonography in diagnosis of chronic
      pancreatitis. The accuracy of diagnosis for ERCP is 84.8%, and is significantly
      higher than that for CT (56.0%, P < 0.01) and ultrasonography (37.8%, P < 0.001).
      The detective rate of abnormal pancreatic duct for ERCP is 91.4%, and is also
      significantly higher than that for CT (80.0%) and ultrasonography (79.7%, P <
      0.05). These data indicated that the clinical features of chronic pancreatitis in
      China is more related to biliary diseases, rather than alcoholism. BT-PABA test
      and ultrasonography are valuable screen examinations, and ERCP is credible
      important examination in diagnosis of chronic pancreatitis.

PMID- 8275825
TI  - [Ventricular late potentials in patients with diabetes mellitus].
AB  - Ventricular late potentials (VLP) was measured in 31 normal subjects, 31 coronary
      heart disease (CHD) patients and 31 diabetic patients whose ECG and UCG were
      normal. Matched control study was used. The result revealed that the positive
      rates of VLP of CHD group (45.16%) was significantly higher than that of diabetic
      group without clinical cardiomyopathy (19.35%, P < 0.05), and diabetic group was
      significantly higher than that of normal subjects (0%, P < 0.05). Although
      electrocardiogram and echocardiography were normal in all the diabetic patients,
      the VLP positive rate was 19.35%. Experimental and clinical studies had shown a
      positive correlation between the duration of late potentials, malignent
      ventricular arrhythmia and sudden cardiac death so that measurement of VLP might
      be a new and valuable technique to detect subclinical diabetic cardiomyopathy,
      and to predict ventricular arrhythmia attack and sudden cardiac death in diabetic
      patients.

PMID- 8275826
TI  - [Antibodies to Klebsiella pneumoniae in ankylosing spondylitis].
AB  - This study was performed to evaluate the involvement of Klebsiella pneumoniae
      (Kp) in ankylosing spondylitis. Serum IgA, IgG and IgM antibodies to Kp were
      measured with ELISA in 60 patients with ankylosing spondylitis (AS), 28 patients
      with rheumatoid arthritis (RA) and 45 healthy individuals. A marked elevation of
      IgA antibody to Kp was detected in the sera of patients with AS, compared to that
      in patients with RA (P < 0.02) and healthy controls (P < 0.001). The positive
      rate of antibodies to Kp was 55% in patients with active AS, significantly higher
      than that in patients with inactive AS (16.7%, P < 0.01), patients with RA
      (17.8%, P < 0.05) and healthy controls (4.4%, P < 0.001). Stool culture for Kp
      was carried out in 15 of the 60 patients with AS simultaneously, 3 (20%) of them
      were positive. Our results are in line with the previously published findings
      suggesting that Kp may play a role in the pathogenesis of AS.

PMID- 8275827
TI  - [HATP chemotherapy combined with Chinese traditional medications in treating
      acute promyelocytic leukemia].
AB  - 18 patients with acute promyelocytic leukemia (APL) were treated with HATP
      (Harringtonine, Adriamycin, Thioguanine, Prednisone) chemotherapy combined with
      chinese traditional medications. These medications are known to strengthen vital
      energy, promote blood circulation, remove stasis and clear toxic materials. 16
      patients had complete remission (88.8%) and one partial remission with a total
      effective rate of 94.4%. Complete remission (CR) was achieved after 3 to 4
      courses of treatment in most of the cases. 14 patients were still in CR at the
      completion of this study and the average duration of survival was 40.5 months.
      With the various therapeutic actions mentioned above, the traditional medications
      might decrease the toxicity of chemotherapy, reduce its side effects and prevent
      the occurrence of DIC. The combined use of traditional medications with
      chemotherapy may increase the rate and duration of CR as well as prolong the
      survival.

PMID- 8275828
TI  - [Current status of research in ultraviolet blood irradiation therapy].

PMID- 8275829
TI  - [Auranofin in the treatment of rheumatoid arthritis: a multicenter double-blind
      prospective clinical trial].

PMID- 8275830
TI  - [Portal high flow state in dogs].
AB  - To make an animal model of portal high blood flow, a retrograde portacaval shunt
      (PCS) was designed. A regular side-to-side PCS with large stoma was performed
      first, followed by the ligation of the vena cava just proximal to the
      anastomosis. Thus the whole amount of blood of the lower half body turned its
      flow into the portal system. Portal hypervolemic model was made in 11 dogs, The
      portal hemodynamics was studied by duplex before operation and 10 days, 20 days
      and 4 months after operation. In the 10th day the 20th day and the 4th month
      after operation, laparotomy was done again for observing FPP, portal collateral
      circulation, and liver biopsy. The portal high flow state was maintained
      constantly and FPP elevated in different degrees. The portal collateral
      circulation and the pathological change of the liver was not remarkable. The
      function of the liver was not damaged. The portal high flow state was proved not
      to cause real clinical portal hypertension, while the elevation of portal
      resistance was the important initiating factor for formation of portal
      hypertension.

PMID- 8275831
TI  - [Hemodynamics of portal system using color ultrasonography and direct pressure
      measurement before and after pericardial devascularization].
AB  - Controlled study on the portal hemodynamics was carried out before and after
      pericardial devascularization in 23 patients with portal hypertension. Color
      ultrasonography detected LGV in 87% of the patients, total prehepatic shunt
      volume was larger than 46.92%, That through SV more than 15. 48%, and LGV about
      15.97%. Hence the total volume shunted through gastrosplenic region was more than
      31.45%. Postoperative FPP was significantly decreased (P < 0.05) and SOPP and
      gastris wall venous pressure increased (P < 0.01). Postoperative PVF did not
      change significantly. When the ratio of SAV to SVF was less than 1.0,
      postoperative PVF was significantly increased (P < 0.05). Shunt surgery is the
      treatment of choice. In the case when the ratio in larger than 1.0, PVF may,
      decrease (P < 0.01); Patients should receive devascularization. When SVF plus
      SMVF is greater than PVF, patients should be operated on only with splenectomy or
      devascularization.

PMID- 8275832
TI  - [Hemodynamic changes after combination operation in cirrhotic patients with
      portal hypertension].
AB  - Hemodynamic changes of the portal system were investigated with pulsed Doppler
      ultrasound device in normal controls and patients with portal hypertension
      treated by combination surgical technique. It was found that the diameter and
      blood flow of the portal vein, splenic vein and superior mesenteric vein were
      larger than those of normal controls. Whereas the velocity of blood flow was
      lower than that of normal controls. FPP decreased by 31.3% after combination
      operation: 7.3% after splenectomy; There was a positive correlation between FPP
      and blood flow of splenic artery. The portal blood flow decreased by 42% after
      disconnection and 62.6% after combination operation. The blood flow of superior
      mesenteric vein after disconnection increased by 38%. The decrease of portal
      blood flow after disconnection was positively correlated with the blood flow of
      the splenic vein. Combination operation is a simple and rational procedure with a
      good effect in stopping hemorrhage, reducing portal vein pressure, and preventing
      recurrence of esophageal varices.

PMID- 8275833
TI  - [The effects of cimetidine on splanchnic hemodynamics in cirrhotic patients with
      portal hypertension].
AB  - The effects of histamine H2-receptor antagonist cimetidine on the splanchnic
      hemodynamics were investigated in 24 cirrhotic patients with portal hypertension
      and on cardiac output (CO) in 12 of the 24 patients. Cimetidine given
      intravenously at a dose of 0.4g significantly decreased wedged hepatic venous
      pressure (-19%, P < 0.01) and hepatic venous pressure gradient (-29%, P < 0.01).
      The drug also slightly increased left ventricular ejection fraction (+4.1%, P <
      0.01). These results show that cimetidine effectively reduce portal venous
      pressure and not hinder the pump function of the heart.

PMID- 8275834
TI  - [Pressure topography of the portal vein system and its clinical implications].
AB  - Pressure topography of the portal vein system was investigated in 10 healthy dogs
      and 26 patients with portal hypertension. The pressure in all of the tributaries
      of the portal vein was significantly higher than that of the portal trunk in
      healthy dogs, with the pressure of left gastric vein being the highest. The
      normal pressure gradient and the hepatopetal blood flow were evidently shown. In
      case of portal hypertension, the pathophysiologic pressure topography of the
      portal venenous system was miscellaneous with the pressure of left gastric vein
      being lower than that of the portal trunk in 41.7% of the 26 patients, a
      phenomenon suggestive of effective decompression of the portal vein by the
      development of esophagogastriv varix.

PMID- 8275835
TI  - [Preliminary study on hemodynamics in post hepatitic cirrhotic patients with
      portal hypertension (PCPH) using Doppler ultrasound].
AB  - Hemodynamics was studied in normal volunteers and pre- and postoperative patients
      with PCPH using Doppler ultrasound. There was a systemic hyperdynamic circulatory
      state in patients with PCPH derived mainly from hyperdynamic splenic circulatory
      state. Congestion index (CI) of portal vein greater than 0.1cm. s, splenic vein
      cross section area greater than 0.6cm2, and SVF/PVF greater than 50%, all of
      these are the hemodynamic diagnostic criterion of PCPH. Both portasystemic shunt
      and porta-azygous devascularization lowered the hyperdynamic circulatory state of
      PCPH.

PMID- 8275836
TI  - [Endoscopic sclerotic therapy for ruptured esophageal varix: an analysis of 73
      cases].
AB  - Seventy-three patients with bleeding esophageal varices were treated by
      transesophageal injection of sclerosing agent through fiberoptic gastroscope
      (EIS). Hemostasis was noted in 63 cases (86.3%). The success rate was 100% among
      those classified as Child A & B and 79.59% in Child C patients. Hemostasis was
      achieved after repeated EIS in 90.2% of the patients. Bleeding stopped in 82.14%
      of the patients who failed to respond to balloon tamponade and in 95.65% of the
      patients with recurrent bleeding after open surgery. The recurrence rate of
      bleeding esophageal varices after EIS was 13.7% and the mortality rate was
      15.07%. EIS was generally performed in the first week of hemorrhage, thereafter,
      it was repeated at a 4-14 days interval. EIS was a simple and safe procedure with
      a high percentage of immediate hemostasis and a comparatively low mortality. It
      could be used to tide some poor risk patients over the crisis for possibly
      further surgery.

PMID- 8275837
TI  - [Endoscopic ligature of the esophageal varix].
AB  - 85 Patients with esophageal varix were treated by endoscopic ligature. Immediate
      hemostasis was obtained after the procedure in 36 of 39 patients with active
      bleeding esophageal varix (92.3%). The varix disappeared in 50 (58.5%) of the 85
      patients after consecutive 3 to 4 procedures and ameliorated in the remaining
      patients.

PMID- 8275838
TI  - [Fourteen cases of Riedel's struma: review of the literature].
AB  - Riedel's struma, a disorder of unknown aetiology, shows that aggressive fibrosis
      replaces the normal structure of the thyroid. The fibrosis characteristically
      spreads beyond the capsule with involvement of the adjacent structures. Fourteen
      patients were encountered from 4501 thyroidectomies at this hospital in a period
      of 33 years. The aetiology, pathology, clinical features and methods of treatment
      were discussed.

PMID- 8275839
TI  - [Diagnosis and treatment of causes of fever after open heart surgery].
AB  - The causes of fever in 171 cases 10 days after 1527 cases of open heart surgery
      were analysed. The common noninfectious causes of fever were postpericardiotomy
      syndrome (35.8%) and drug fever (26.9%). The infectious causes of fever were
      respiratory system infection (18.1%), chest wall and incision infection (9.9%),
      infectious endocarditis (7.0%) and transfusion malaria (2.4%). In this paper, the
      diagnosis, prevention and treatment of common causes of fever after open heart
      surgery were discussed. The authors believed that etiologic diagnosis of fever
      and reasonable antibiotic use were key measures.

PMID- 8275840
TI  - [Diagnosis and surgical management of gastroesophageal reflux disease].
AB  - Fifty-four patients with gastroesophageal reflux disease were treated surgically.
      Fourty-six patients were sliding hiatal hernia and 8 were short esophagus. In
      addition to barium meal exam, endoscopic examination and esophageal function
      testing were also helpful in clinical evaluation of patients and selection of
      antireflux surgery. Nissen fundoplication was the most use in this series.
      Following-up showed that 64.8 percent completely relieved and 31.5 percent
      improved.

PMID- 8275841
TI  - [Management of variceal ulcer in lower extremities].
AB  - Percutaneous ligation around the main nutritional skin area or variceal ulcer
      instead of avulsion and phlebectomy was performed in 194 of 196 lower extremities
      with great saphenous varix after proper dealing with the primary lesion in the
      profound veins. All patients were followed up from 6 months to 6 years with no
      recurrence.

PMID- 8275842
TI  - [Transplantation of free medial leg skin flap to bridge over electric burns at
      wrist].
AB  - Twelve wrists (in 11 patients) with electric burns were covered by the
      transplantation of free medial leg skin flaps. It was successful in 10 but failed
      in 2. Our experience is summarized as following: 1. The skin flaps can serve as
      bridge to allow blood to go through as well as good coverage for the wound. When
      the ulnar artery and the radial artery are injured, we can obtain a long segment
      of the posterior tibial artery, and portions of it can be used to repair these
      arteries. In this series two hands were saved with good function in three years
      follow-up. 2. The sites of the skin flaps are concealed. Harvesting of the flaps
      does not impaired the function of the donor site. Thickness of the flaps is
      adequate. The flaps are not excessively bulky. The anatomical site of the
      posterior tibial artery is constant. The calibre of the posterior tibial artery
      is similar to that of the radial arteries. The rate of success of the operation
      is high.

PMID- 8275843
TI  - [Preparation and clinical application of human dermis collagen protein-membrane].
AB  - The discarded human dermis was collected after skin grafting and the collagen was
      extracted by using pepsin-controlling degration method. Under vacuum and frozen
      condition, the white-clear, frothy, pliable collagen membrane of the human dermis
      was obtained. The collagen membrane can be easily stored, transported, and used
      under normal temperature. The collagen membrane with spongiform structure has
      better water-permeability, adhesiveness, flexibility and less antigen. It was
      used to cover the wound surface of crust-excised in 7 cases of burn with
      satisfactory results.

PMID- 8275844
TI  - [Management of primary retroperitoneal tumors].
AB  - Of 78 patients with primary retroperitoneal tumors, 38 were male and 40 female on
      the average 41 years age. Twenty-seven patients (35%) had benign tumors, 51 (65%)
      malignant. The biggest tumor weighted 28.5 kg. Complete resection was performed
      in 57 patients (73.1%), palliative in (11.5%). 64.7% of the patients with
      malignant tumor underwent complete resection with 1, 3, 5 year survival rates of
      84.9%, 72.6% and 62.2%, respectively. Our experience showed that CT not only
      detected the mass, but also clearly defined its relationship to the adjacent
      viscera and vessel. It is suggested that embloc resection of the entire tumor
      with involved organs and tissues be used to decrease local recurrence and enhance
      the survival rate. The importance of aggressive reoperation for recurrence was
      also emphasized.

PMID- 8275845
TI  - [Postoperative pulmonary tissue changes after autogenous lung and artificial lung
      bypass].
AB  - The changes in autogenous lung oxygenation and artificial lung during
      cardiopulmonary bypass (CPB) were compared. The results of our investigation
      showed that autogenous lung oxygenation is less injurious to the lung than bubble
      oxygenation and is more physiological. We think that during autogenous lung
      bypass and open heart surgery, the lung is functioning physiologically and is
      supplied with normal amount of oxygen, while using bubble oxygenation for CPB the
      native lung is the only nonperfused organ and lung function being insulted by
      pulmonary ischemia which is one of the most important reason for pulmonary injury
      after CPB.

PMID- 8275846
TI  - [Morphological study of the microcirculation in regional cortical bones affected
      by internal fixation plates].
AB  - In order to elucidate the potential role of bone microcirculation in the
      development of plate-induced regional osteoporosis, microangiography was used to
      observe the morphological changes of microcirculation in cortical bones obtained
      from intact rabbit tibiae on which plates of two different stiffness had been
      fixed for comparison. The results indicated that both rigid stainless steel
      plates and less rigid methyl methacrylate plates could induce the bone
      microcirculation under and opposite the plate to undergo a changing process from
      early depression to later reactive recruitment. The features of the
      microcirculation recruitment as shown in vascular number, arrangement and
      dilatation varied with different stiffness plates and in different locations, and
      might also have bearing on the formation of osteoporosis.

PMID- 8275847
TI  - [Effect of radix salviae miltiorrhizae on the mitotic activity of osteoblast-like
      cells isolated from chicken embryo calvariae cultured in vitro].
AB  - Chicken embryo calvariae cultured in vitro, could yield 3 types of osteoblast
      like cells, which differed in morphology. They were the spindle-shaped cells,
      globular cells, and squamous cells. Of these, the squamous cell was the chief
      cellular component, while both the spindle-shaped cells and the globular cells
      gradually transformed into squamous cells. Administration of Radix Salviae
      Miltiorrhizae rendered more rapid growth of the osteoblast-like cells in the
      early stage of culture. After 17-day of culture, when both the control group
      cells and the treated, group cells became quite confluent, 3H-Thymidine labelling
      and radioautographic study revealed a very statistically significant increase in
      the number of cells, bearing silver grains over the nucleus area in the treated
      group, as compared with the control (P < 0.001). Since osteoblasts play a pivotal
      role in fracture healing, administration of Radix Salviae Miltiorrhizae can exert
      favourable influence on bone repair through increasing the number of osteoblasts.

PMID- 8275848
TI  - [A new technique for colon-anal anastomosis by intra-anal circular ligation].
AB  - Using self-made supporting tube, we performed colon-anal anastomosis in 48
      radical resections of low rectal carcinoma, to save the anal canal and sphincter.
      The anastomoses were completed without suturing and the results were
      satisfactory. Postoperative follow up revealed that the bowel movement and
      sphincteric function were all satisfactory. The rate of anastomotic leak was
      about 4% and there was no operative mortality. This new technic is simple, safe
      and easy to perform, and is considered to be a promising procedure for colon-anal
      anastomosis after resection of low rectal cancer.

PMID- 8275849
TI  - Interaction between splotch (Sp) and curly tail (ct) mouse mutants in the
      embryonic development of neural tube defects.
AB  - The mouse mutations splotch (Sp) and curly tail (ct) both produce spinal neural
      tube defects with closely similar morphology, but achieve this by different
      embryonic mechanisms. To determine whether the mutants may interact during
      development, we constructed mice carrying both mutations. Double heterozygotes
      exhibited tail defects in 10% of cases, although the single heterozygotes do not
      express this phenotype. Backcrosses of double heterozygotes to ct/ct produced
      offspring with an elevated incidence of neural tube defects, both spina bifida
      and tail defects, compared with a control backcross in which Sp was not involved.
      Use of the deletion allele Sp2H permitted embryos carrying a splotch mutation to
      be recognised by polymerase chain reaction assay. This experiment showed that
      only embryos carrying Sp2H develop spina bifida in the backcross with ct/ct,
      suggesting that the genotype Sp2H/+, ct/ct is usually lethal around the time of
      birth as a result of severe disturbance of neurulation. The interaction between
      Sp and ct was investigated further by examining embryos in the backcross for
      developmental markers of the Sp/Sp and ct/ct genotypes. Sp/Sp embryos
      characteristically lack neural crest derivatives, such as dorsal root ganglia,
      and die on day 13 of gestation. Double mutant embryos from the backcross did not
      exhibit either of these characteristics suggesting that homozygosity for ct does
      not cause Sp/+ embryos to develop as if they were of genotype Sp/Sp. The angle of
      ventral curvature of the posterior neuropore region is enhanced in affected ct/ct
      embryos whereas it was found to be reduced in Sp/Sp embryos compared with their
      normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275850
TI  - The role of the ovarian tumor locus in Drosophila melanogaster germ line sex
      determination.
AB  - The locus ovarian tumor (otu) is involved in several aspects of oogenesis in
      Drosophila melanogaster. The possible role of otu in the determination of the
      sexual identity of germ cells has not been extensively explored. Some otu alleles
      produce a phenotype known as ovarian tumors: ovarioles are filled with numerous
      poorly differentiated germ cells. We show that these mutant germ cells have a
      morphology similar to primary spermatocytes and that they express male germ line
      specific reporter genes. This indicates that they are engaged along the male
      pathway of germ line differentiation. Consistent with this conclusion, we found
      that the splicing of Sex-lethal (Sxl) pre-mRNAs occurs in the male-specific mode
      in otu-transformed germ cells. The position of the otu locus in the regulatory
      cascade of germ line sex determination has been studied by using mutations that
      constitutively express the feminizing activity of the Sxl gene. The sexual
      transformation of the germ cells observed with several combinations of otu
      alleles can be reversed by constitutive expression of Sxl. This shows that otu
      acts upstream of Sxl in the process of germ line sex determination. Other
      phenotypes of otu mutations were not rescued by constitutive expression of Sxl,
      suggesting that several functions of otu are likely to be independent of sex
      determination. Finally, we show that the gene dosage of otu modifies the
      phenotype of ovaries heterozygous for the dominant alleles of ovo, another gene
      involved in germ line sex determination. One dose of otu+ enhances the ovoD
      ovarian phenotypes, while three doses partially suppress these phenotypes.
      Synergistic interaction between ovoD1 and otu alleles leads to the occasional
      transformation of chromosomally female germ cells into early spermatocytes. These
      interactions are similar to those observed between ovoD and one allele of the
      sans fille (snf) locus. Altogether, our results imply that the otu locus acts,
      along with ovo, snf, and Sxl, in a pathway (or parallel pathways) required for
      proper sex determination of the female germ line.

PMID- 8275851
TI  - cAMP-dependent protein kinase differentially regulates prestalk and prespore
      differentiation during Dictyostelium development.
AB  - We and others have previously shown that cAMP-dependent protein kinase (PKA)
      activity is essential for aggregation, induction of prespore gene expression and
      multicellular development in Dictyostelium. In this manuscript, we further
      examine this regulatory role. We have overexpressed the Dictyostelium PKA
      catalytic subunit (PKAcat) in specific cell types during the multicellular
      stages, using prestalk and prespore cell-type-specific promoters to make PKA
      activity constitutive in these cells (independent of cAMP concentration). To
      examine the effects on cell-type differentiation, we cotransformed the PKAcat
      expressing vectors with reporter constructs expressing lacZ from four cell-type
      specific promoters: ecmA (specific for prestalk A cells); ecmB (specific for
      prestalk B and anterior-like cells in the slug); ecmB delta 89 (specific for
      stalk cells); and SP60 (prespore-cell-specific). By staining for beta
      galactosidase expression histologically at various stages of development in
      individual strains, we were able to dissect the morphological changes in these
      strains, examine the spatial localization of the individual cell types, and
      understand the possible roles of PKA during multicellular development. Expression
      of PKAcat from either the ecmA or ecmB prestalk promoters resulted in abnormal
      development that arrested shortly after the mound stage, producing a mound with a
      round apical protrusion at the time of tip formation. Prestalk A and prestalk B
      cells were localized in the central region and the apical mound in the terminal
      differentiated aggregate, while prespore cells showed an aberrant spatial
      localization. Consistent with a developmental arrest, these mounds did not form
      either mature spores or stalk cells and very few cells expressed a stalk-cell
      specific marker. Expression of PKAcat from the prespore promoter resulted in
      abnormal morphogenesis and accelerated spore cell differentiation. When cells
      were plated on agar, a fruiting body was formed with a very large basal region,
      containing predominantly spores, and a small, abnormal sorocarp. Mature spore
      cells were first detected by 14 hours, with maximal levels reached by 18-20
      hours, in contrast to 24-26 hours in wild-type strains. When cells were plated on
      filters, they produced an elongated tip from a large basal region, which
      continued to elongate as a tubular structure and produce a 'slug-like' structure
      at the end. The slug was composed predominantly of prestalk cells with a few
      prespore cells restricted to the junction between the 'slug' and tube. As the
      slug migrated, these prespore cells were found in the tube, while new prespore
      cells appeared at the slug/tube junction, suggesting a continual differentiation
      of new prespore cells at the slug's posterior.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8275852
TI  - Size regulation and morphogenesis: a cellular analysis of skeletogenesis in the
      sea urchin embryo.
AB  - The formation of the skeleton is a central event in sea urchin morphogenesis. The
      skeleton serves as a framework for the larval body and is the primary determinant
      of its shape. Previous studies have shown that the size of the skeleton is
      invariant despite wide experimentally induced variations in the number of
      skeleton-forming primary mesenchyme cells (PMCs). In the present study, we have
      used PMC transplantation, fluorescent cell markers and confocal laser scanning
      microscopy to analyze cellular aspects of skeletal patterning. Labeling of
      embryos with 5-bromodeoxyuridine demonstrates that the entire embryonic phase of
      skeletal morphogenesis occurs in the absence of PMC division. During
      embryogenesis, skeletal rods elongate by one of two mechanisms; either preceded
      by a cluster (plug) of PMCs or by extending along an existing PMC filopodial
      cable. Elongation of skeletal rods occurs exclusively by the addition of new
      material at the rod tips, although radial growth (increase in rod thickness)
      occurs along the length of the rods. Photoablation of a distinctive region of
      ectoderm cells at the arm tip results in an inhibition of skeletal rod
      elongation, indicating that a local ectoderm-PMC interaction is required for
      skeletal growth. The regulation of skeletal patterning was also examined in
      embryos that had been microinjected with additional PMCs and in half-sized larvae
      derived from blastomeres isolated at the 2-cell stage. Microinjection of 50-100
      PMCs into the blastocoel at the mesenchyme blastula stage leads to an increase in
      the numbers of PMCs along all skeletal rods and a two-fold increase in the number
      of cells in the plugs, yet no increase in the length of the skeletal rods. The
      length of the anal rods can, however, be increased by microinjecting
      developmentally 'young' PMCs into the arm tips of late stage embryos. We find
      that the rate of skeletal rod elongation is independent of both the mode of rod
      growth (chain or plug) and the number of PMCs in the plug at the growing rod tip.
      Instead, the rate of elongation appears to be strictly regulated by the quantity
      of ectodermal tissue present in the embryo. These studies provide new information
      concerning normal mechanisms of skeletal growth and patterning and lead us to
      propose a model for the regulation of skeleton size based upon an intrinsic PMC
      'clock' and an ectoderm-derived signal that regulates the rate of skeletal rod
      elongation.

PMID- 8275853
TI  - Multiple RNA regulatory elements mediate distinct steps in localization of oskar
      mRNA.
AB  - Pattern formation in the early development of many organisms relies on localized
      cytoplasmic proteins, which can be prelocalized as mRNAs. The Drosophila oskar
      gene, required both for posterior body patterning and germ cell determination,
      encodes one such mRNA. Localization of oskar mRNA is an elaborate process
      involving movement of the transcript first into the oocyte from adjacent
      interconnected nurse cells and then across the length of the oocyte to its
      posterior pole. We have mapped RNA regulatory elements that direct this
      localization. Using a hybrid lacZ/oskar mRNA, we identify several elements within
      the oskar 3' untranslated region that affect different steps in the process: the
      early movement into the oocyte, accumulation at the anterior margin of the oocyte
      and finally localization to the posterior pole. This use of multiple cis-acting
      elements suggests that localization may be orchestrated in a combinatorial
      fashion, thereby allowing localized mRNAs with ultimately different destinations
      to employ common mechanisms for shared intermediate steps.

PMID- 8275854
TI  - Fertilisation and thimerosal stimulate similar calcium spiking patterns in mouse
      oocytes but by separate mechanisms.
AB  - Exposure of freshly ovulated mouse oocytes to a fertilising spermatozoon,
      thimerosal, Sr2+ or acetylcholine induced similar Ca2+ spiking responses. We
      propose that each of the four agents reduces the threshold for Ca2+ release from
      internal stores, but by different mechanisms. All agents except thimerosal
      stimulated oocyte activation, but thimerosal caused dissassembly of the meiotic
      spindle and thus prevented progress into interphase. Dithiothreitol (DTT)
      completely blocked and reversed the spiking responses induced by thimerosal, but
      facilitated and accelerated those induced by spermatozoa, Sr2+ and acetylcholine.
      The stimulatory effect of DTT was not simply a consequence of progress into
      interphase, but was attributable, at least in part, to an enhancement of divalent
      cation entry, as measured by Mn2+ quench analysis of fura-2 in both fertilised
      and unfertilised oocytes. Possible mechanisms by which DTT might achieve its
      effects are discussed.

PMID- 8275855
TI  - Preimplantation mouse embryos express a cell surface receptor for tissue
      plasminogen activator.
AB  - The serine protease tissue-plasminogen activator (t-PA) has previously been shown
      to be intracellular in mouse secondary oocytes and extracellular in fertilized
      eggs. Here we demonstrate that extracellular t-PA activity is bound to the
      surface of the fertilized egg. The level of t-PA activity associated with
      preimplantation mouse embryos decreases in the 2-cell stage embryo, then
      increases in 4-cell and morula stage embryos. However, morulae grown in culture
      from fertilized eggs lack t-PA activity but are able to bind exogenously added
      mouse t-PA. Additionally, northern analysis indicates that preimplantation
      embryos do not contain detectable levels of t-PA mRNA. Therefore, the enzyme
      activity associated with 4-cell and morula stage embryos in vivo is derived from
      t-PA present in the oviduct lumen that binds the embryo, and not from protein
      produced from translation of embryonic mRNA. The binding activity is species and
      protein specific in that neither mouse urokinase-type plasminogen activator (u
      PA) nor human t-PA bind to cultured morulae. Furthermore, binding activity is
      dose-dependent and saturable, and does not require the active site of t-PA. These
      data indicate that a cell surface-specific t-PA-binding activity exists in the
      preimplantation mouse embryo and may localize function and concentrate the
      proteolytic activity of t-PA in early mouse development.

PMID- 8275856
TI  - FGF-4 maintains polarizing activity of posterior limb bud cells in vivo and in
      vitro.
AB  - The polarizing region is a major signalling tissue involved in patterning the
      tissues of the vertebrate limb. The polarizing region is located at the posterior
      margin of the limb bud and can be recognized by its ability to induce additional
      digits when grafted to the anterior margin of a chick limb bud. The signal from
      the polarizing region operates at the tip of the bud in the progress zone, a zone
      of undifferentiated mesenchymal cells, maintained by interactions with the apical
      ectodermal ridge. A number of observations have pointed to a link between the
      apical ectodermal ridge and signalling by the polarizing region. To test this
      possibility, we removed the posterior apical ectodermal ridge of chick wing buds
      and assayed posterior mesenchyme for polarizing activity. When the apical
      ectodermal ridge is removed, there is a marked decrease in polarizing activity of
      posterior cells. The posterior apical ectodermal ridge is known to express FGF-4
      and we show that the decrease in polarizing activity of posterior cells of wing
      buds that normally follows ridge removal can be prevented by implanting a FGF-4
      soaked bead. Furthermore, we show that both ectoderm and FGF-4 maintain
      polarizing activity of limb bud cells in culture.

PMID- 8275857
TI  - Distribution of tudor protein in the Drosophila embryo suggests separation of
      functions based on site of localization.
AB  - Mutations in the tudor locus of Drosophila affect two distinct determinative
      processes in embryogenesis; segmentation of the abdomen and determination of the
      primordial germ cells. The distribution of tudor protein during embryogenesis,
      and the effect of various mutations on its distribution, suggest that tudor
      protein may carry out these functions separately, based on its location in the
      embryo. The protein is concentrated in the posterior pole cytoplasm (germ plasm),
      where it is found in polar granules and mitochondria. Throughout the rest of the
      embryo, tudor protein is associated with the cleavage nuclei. Mutations in all
      maternal genes known to be required for the normal functioning of the germ plasm
      eliminate the posterior localization of tudor protein, whereas mutations in genes
      required for the functioning of the abdominal determinant disrupt the
      localization around nuclei. Analysis of embryos of different maternal genotypes
      indicates that the average number of pole cells formed is correlated with the
      amount of tudor protein that accumulates in the germ plasm. Our results suggest
      that tudor protein localized in the germ plasm is instrumental in germ cell
      determination, whereas nuclear-associated tudor protein is involved in
      determination of segmental pattern in the abdomen.

PMID- 8275858
TI  - XASH-3, a novel Xenopus achaete-scute homolog, provides an early marker of planar
      neural induction and position along the mediolateral axis of the neural plate.
AB  - We have isolated a novel Xenopus homolog of the Drosophila achaete-scute genes,
      called XASH-3. XASH-3 expression is neural specific and is detected as early as
      stage 11 1/2, making it one of the earliest markers of neural induction so far
      described. Moreover, XASH-3 expression within the neural plate is regionally
      restricted. Transverse bands of XASH-3 mRNA mark discrete positions along the
      anteroposterior axis, while longitudinal bands mark a discrete position along the
      mediolateral axis. This latter site of XASH-3 expression appears to demarcate the
      prospective sulcus limitans, a boundary zone that later separates the
      functionally distinct dorsal (alar) and ventral (basal) regions of the spinal
      cord. In sandwich explants lacking any underlying mesoderm, XASH-3 is expressed
      in longitudinal stripes located lateral to the midline. This provides the first
      indication that planar or midline-derived inductive signals are sufficient to
      establish at least some aspects of positional identity along the mediolateral
      axis of the neural plate. By contrast, the transverse stripes of XASH-3
      expression are not detected, suggesting that this aspect of anteroposterior
      neural pattern is lost or delayed in the absence of vertically passed signals.
      The restricted mediolateral expression of XASH-3 suggests that mediolateral
      patterning of the neural plate is an early event, and that this regionalization
      can be achieved in the absence of inducing signals derived from underlying
      mesoderm.

PMID- 8275859
TI  - Even-numbered rhombomeres control the apoptotic elimination of neural crest cells
      from odd-numbered rhombomeres in the chick hindbrain.
AB  - Neural crest cells originate at three discontinuous levels along the rostrocaudal
      axis of the chick rhombencephalon, centred on rhombomeres 1 and 2, 4 and 6,
      respectively. These are separated by the odd-numbered rhombomeres r3 and r5 which
      are depleted of migratory neural crest cells. Here we show elevated levels of
      apoptosis in the dorsal midline of r3 and r5, immediately following the formation
      of these rhombomeres at the developmental stage (10-12) when neural crest cells
      would be expected to emerge at these neuraxial levels. These regions are also
      marked by their expression of members of the msx family of homeobox genes with
      msx-2 expression preceding apoptosis in a precisely colocalised pattern. In vitro
      and in ovo experiments have revealed that r3 and r5 are depleted of neural crest
      cells by an interaction within the neural epithelium: if isolated or distanced
      from their normal juxtaposition with even-numbered rhombomeres, both r3 and r5
      produce migrating neural crest cells. When r3 or r5 are unconstrained in this
      way, allowing production of crest, msx-2 expression is concomitantly down
      regulated. This suggests a correlation between msx-2 and the programming of
      apoptosis in this system. The hindbrain neural crest is thus produced in discrete
      streams by mechanisms intrinsic to the neural epithelium. The crest cells that
      enter the underlying branchial region are organised into streams before they
      encounter the mesodermal environment lateral to the neural tube. This contrasts
      sharply with the situation in the trunk where neural crest production is
      uninterrupted along the neuraxis and the segmental accumulation of neurogenic
      crest cells is subsequently founded on an alternation of permissive and non
      permissive qualities of the local mesodermal environment.

PMID- 8275860
TI  - Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS
      and limb buds.
AB  - Mutation and expression studies have implicated the Wnt gene family in early
      developmental decision making in vertebrates and flies. In a detailed comparative
      analysis, we have used in situ hybridization of 8.0- to 9.5-day mouse embryos to
      characterize expression of all ten published Wnt genes in the central nervous
      system (CNS) and limb buds. Seven of the family members show restricted
      expression patterns in the brain. At least three genes (Wnt-3, Wnt-3a, and Wnt
      7b) exhibit sharp boundaries of expression in the forebrain that may predict
      subdivisions of the region later in development. In the spinal cord, Wnt-1, Wnt
      3, and Wnt-3a are expressed dorsally, Wnt-5a, Wnt-7a, and Wnt-7b more ventrally,
      and Wnt-4 both dorsally and in the floor plate. In the forelimb primordia, Wnt-3,
      Wnt-4, Wnt-6 and Wnt-7b are expressed fairly uniformly throughout the limb
      ectoderm. Wnt-5a RNA is distributed in a proximal to distal gradient through the
      limb mesenchyme and ectoderm. Along the limb's dorsal-ventral axis, Wnt-5a is
      expressed in the ventral ectoderm and Wnt-7a in the dorsal ectoderm. We discuss
      the significance of these patterns of restricted and partially overlapping
      domains of expression with respect to the putative function of Wnt signalling in
      early CNS and limb development.

PMID- 8275861
TI  - Heterotopic transplantation of presumptive placodal ectoderm changes the fate of
      sensory neuron precursors.
AB  - The placode-derived cranial sensory neurons of the vestibular and nodose ganglia
      in avian embryos exhibit differences in neurite growth rate and the duration of
      neurotrophin-independent survival in vitro that arise prior to gangliogenesis and
      target contact (Davies, A. M. (1989) Nature 337, 553-555; Vogel, K. S. and
      Davies, A. M. (1991) Neuron 7, 819-830). To ascertain the state of commitment of
      presumptive placodal ectoderm to differentiate into neurons of the vestibular or
      nodose type, we performed heterotopic transplantation of labelled presumptive
      placodal ectoderm at E1.5 in the chicken embryo. We then assayed transplant
      derived neurons for hindbrain innervation patterns, neurite growth and survival
      at E3.5. We show that presumptive placodal ectoderm is not determined to give
      rise to neurons of the vestibular or nodose phenotype at E1.5. Explantation of
      presumptive placodal ectoderm at E1.5 showed that this ectoderm is also not
      specified to differentiate into neurons at this stage. In addition, we
      demonstrate that non-neurogenic ectoderm from the trunk can give rise to nodose
      type neurons when transplanted heterotopically to the nodose region.

PMID- 8275862
TI  - Cortical cytoplasm, which induces dorsal axis formation in Xenopus, is
      inactivated by UV irradiation of the oocyte.
AB  - Localized maternal determinants control the formation of dorsal axial structures
      in Xenopus embryos. To examine the spatial distribution of dorsal determinants,
      we injected cytoplasm from various regions of the egg and 16-cell embryo into the
      ventral vegetal cells of a 16-cell recipient embryo. Cortical cytoplasm from the
      egg vegetal surface induced the formation of a secondary dorsal axis in 53% of
      recipients. In contrast, animal cortical, equatorial cortical and vegetal deep
      cytoplasm never induced secondary axis formation. We also compared the axis
      inducing ability of animal versus vegetal dorsal cortical cytoplasm from 16-cell
      embryos. Significantly more dorsalizing activity was found in vegetal dorsal
      cytoplasm compared to animal dorsal cytoplasm at this stage. Previous work has
      shown that UV irradiation of the vegetal surface of either prophase I oocytes, or
      fertilized eggs, leads to the development of embryos that lack dorsal structures.
      Egg vegetal cortical cytoplasm was capable of restoring the dorsal axis of 16
      cell recipient embryos derived from UV-irradiated oocytes or fertilized eggs. We
      also tested the axis inducing ability of cytoplasm obtained when UV-irradiated
      oocytes and eggs were treated as donors of cytoplasm. While vegetal cortical
      cytoplasm from UV-irradiated fertilized eggs retains its dorsalizing activity,
      cytoplasm obtained from eggs, UV irradiated as oocytes, does not. The egg vegetal
      cortex provides a suitable source for the isolation of maternal dorsal
      determinants. In addition, since UV irradiation of the oocyte vegetal surface
      destroys the dorsalizing activity of transferred cytoplasm, UV can be used to
      further restrict possible candidates for such determinants.

PMID- 8275863
TI  - Cardiovascular development in the zebrafish. I. Myocardial fate map and heart
      tube formation.
AB  - We have analyzed the origin of cardiac progenitors in the zebrafish embryo by
      injection of single blastomeres with a lineage tracer dye, and examined the
      formation of the zebrafish heart tube by serial sectioning of immunostained
      embryos. At the 512-cell stage (early blastula), most cardiac progenitors lie in
      a marginal zone that extends from 90 degrees longitude (midway between the future
      dorsal and ventral axis) through 180 degrees longitude (the future ventral axis)
      to 270 degrees longitude. By focusing on myocardial progenitors located at 90
      degrees (and 270 degrees) longitude, we found that a single cell injected in the
      early blastula can contribute progeny to both the atrium and ventricle. A cell
      injected in the midblastula contributes progeny to either the atrium or
      ventricle, but not both. This analysis suggests that, at least for these
      myocardial progenitors, the atrial and ventricular lineages separate in the
      midblastula. Precardiac cells involute early during gastrulation and turn towards
      the animal pole with other early involuting cells. These cardiogenic cells reach
      the embryonic axis around the 8-somite stage, and there they coalesce to form a
      pair of myocardial tubular primordia on either side of the midline. By the 21
      somite stage, the tropomyosin-immunoreactive myocardial tubes have moved closer
      to each other, and a distinct group of cells, the endocardial progenitor cells,
      sits medially between them. The myocardial tubes then fuse to enclose the
      endocardial cells and form the definitive heart tube. By 22 hours
      postfertilization (26-somite stage), the heart tube is clearly beating. The
      regionalization of cardiac myosin heavy chain expression distinguishes the
      cardiac chambers at this stage, although they are not morphologically delineated
      until 36 hours. This work shows that cardiogenic regions can be identified in the
      early blastula, and that chamber restriction seems to arise in the midblastula.
      Additionally, it provides the basis for embryological perturbation at the single
      cell level, as well as for the genetic analysis of heart tube formation in the
      zebrafish.

PMID- 8275864
TI  - Root development in Arabidopsis: four mutants with dramatically altered root
      morphogenesis.
AB  - A genetic analysis of root development in Arabidopsis thaliana has identified
      mutants that have abnormal morphogenesis. Four of these root morphogenesis
      mutants show dramatic alterations in post-embryonic root development. The short
      root mutation results in a change from indeterminate to determinate root growth
      and the loss of internal root cell layers. The cobra and lion's tail mutations
      cause abnormal root cell expansion which is conditional upon the rate of root
      growth. Expansion is greatest in the epidermal cells in cobra and in the stele
      cells in lion's tail. The sabre mutation causes abnormal cell expansion that is
      greatest in the root cortex cell layer and is independent of the root growth
      rate. The tissue-specific effects of these mutations were characterized with
      monoclonal antibodies and a transgenic marker line. Genetic combinations of the
      four mutants have provided insight into the regulation of growth and cell shape
      during Arabidopsis root development.

PMID- 8275865
TI  - Cellular organisation of the Arabidopsis thaliana root.
AB  - The anatomy of the developing root of Arabidopsis is described using conventional
      histological techniques, scanning and transmission electron microscopy. The root
      meristem is derived from cells of the hypophysis and adjacent cells of the embryo
      proper. The postembryonic organization of the root is apparent in the mature
      embryo and is maintained in the growing primary root after germination. Cell
      number and location is relatively invariant in the primary root, with 8 cortical
      and endodermal cell files but more variable numbers of pericycle and epidermal
      cells. The organisation of cells in lateral roots is similar to that of the
      primary root but with more variability in the numbers of cell files in each
      layer. [3H]thymidine labeling of actively growing roots indicates that a
      quiescent centre of four central cells (derived from the hypophysis) is located
      between the root cap columella and the stele. This plate of four cells is
      surrounded by three groups of cells in, proximal, distal and lateral positions.
      The labeling patterns of these cells suggest that they are the initials for the
      files of cells that comprise the root. They give rise to four sets of cell files:
      the stele, the cortex and endodermis, the epidermis and lateral root-cap and the
      columella. A model of meristem activity is proposed based on these data. This
      description of Arabidopsis root structure underpins future work on the
      developmental genetics of root morphogenesis.

PMID- 8275866
TI  - Asymmetric patterns of gap junctional communication in developing chicken skin.
AB  - To study the pattern of gap junctional communication in chicken skin and feather
      development, we injected Lucifer Yellow into single cells and monitored the
      transfer of the fluorescent dye through gap junctions. Dye coupling is present
      between cells of the epithelium as well as between cells of the mesoderm.
      However, dye transfer did not occur equally in all directions and showed several
      consistent patterns and asymmetries, including: (1) no dye coupling between
      mesoderm and epithelium, (2) partial restriction of dye coupling at the feather
      bud/interbud boundary during early feather bud development, (3) preferential
      distribution of Lucifer Yellow along the anteroposterior axis of the feather
      placode and (4) absence of dye coupling in some epithelial cells. These results
      suggest the presence of preferential pathways of communication that may play a
      role in the patterning of chicken skin.

PMID- 8275867
TI  - Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression
      in embryos of Xenopus laevis.
AB  - To contribute to an understanding of the roles and mechanisms of action of Wnts
      in early vertebrate development, we have characterized the normal expression of
      Xenopus laevis Wnt-5A, and investigated the consequences of misexpression of this
      putative signalling factor. Xwnt-5A transcripts are expressed throughout
      development, and are enriched in both the anterior and posterior regions of
      embryos at late stages of development, where they are found primarily in
      ectoderm, with lower levels of expression in mesoderm. Overexpression of Xwnt-5A
      in Xenopus embryos leads to complex malformations distinct from those achieved by
      ectopic expression of Xwnts -1, -3A, or -8. This phenotype is unlikely to result
      from Xwnt-5A acting as an inducing agent, as overexpression of Xwnt-5A does not
      rescue dorsal structures in UV-irradiated embryos, does not induce mesoderm in
      blastula caps, and Xwnt-5A does not alter the endogenous patterns of expression
      of goosecoid, Xbra, or Xwnt-8. To pursue whether Xwnt-5A has the capacity to
      affect morphogenetic movements, we investigated whether overexpression of Xwnt-5A
      alters the normal elongation of blastula cap explants induced by activin.
      Intriguingly, Xwnt-5A blocks the elongation of blastula caps in response to
      activin, without blocking the differentiation of either dorsal or ventral
      mesoderm within these explants. The data are consistent with Xwnt-5A having the
      potential activity of modifying the morphogenetic movements of tissues.

PMID- 8275868
TI  - How normal is variable, or how variable is normal?
AB  - Variability is an important property of the central nervous system, and it shows
      characteristic changes during infancy and childhood. The large amount of
      variations in the performance of sensomotor functions in infancy is called
      indiscriminate or primary variability. During toddling age the child develops the
      capacity to select adaptive variations, and then automatize them: secondary or
      adaptive variability. The latter is required for the development of motor skills
      during later preschool age and school age. The question 'How normal is variable
      or how variable is normal is a wrong question, as any form of variability must be
      interpreted according to its extent, type and age adequacy.

PMID- 8275869
TI  - Festschrift for Heinz F. R. Prechtl. Papers presented at the Symposium
      Development Neurology--Where Research and Clinical Meet, 17-19 September 1992,
      Groningen, The Netherlands.

PMID- 8275870
TI  - Computer-simulated neural networks: an appropriate model for motor development?
AB  - The idea of an artificial neural network is introduced in a historical context,
      and the essential aspect of it, viz., the modifiable synapse, is compared to the
      aspect of plasticity in the natural nervous system. Based on such an artificial
      neural network, a model is presented for the way in which (the path along which)
      the connectivity in the spinal cord is modified during the period that a newborn
      'learns' to control the movement of his forearm. In this way an automatic
      calibration of the receptors and the antagonists' recruitment of motor units is
      represented. The learning process is described in non-mathematical terminology.
      The model is then shown to be able after learning to reach target angles outside
      the training set of angles, and to be able to relearn when an important receptor
      has been made inoperative. In this way it is shown that the model is able to
      generalize, and that it is robust against at least some damage.

PMID- 8275871
TI  - Mental and motor development in preterm infants: the issue of corrected age.
AB  - This paper addresses the question of whether corrected age needs to be applied to
      both the mental and motor development of preterm infants during the whole of the
      first year. A neglected problem in this respect is that a precise developmental
      index cannot be found with very low or very high raw scores. Using an alternative
      measure of performance (age equivalent deviation score), 36 preterm infants
      without serious medical or neurological problems were compared with 21 full-term
      infants on the Dutch version of the Bayley Mental Scale at the corrected ages of
      12, 18, 24, 39 and 52 weeks and the Psychomotor Scale at 24, 39 and 52 weeks. Our
      findings suggest that full correction should be used in assessing the mental
      development of relatively healthy preterm infants during the second half of the
      first year. Assessments at earlier ages seem to overestimate the mental abilities
      of preterm infants, thus indicating that partial correction should be applied at
      these ages. For motor development during the second half of the first year a
      partial correction would seem more appropriate. The clinical implications of our
      findings are discussed.

PMID- 8275872
TI  - SIDS--a developmental neurological perspective.
AB  - Most SIDS deaths occur between 2 and 4 months of age. Neural transformations may
      be important in SIDS. Evidence of delayed myelination has been found in SIDS
      victims. However a simple neuro-developmental model is insufficient to explain
      SIDS. The age of death profile is reportedly similar for pre-term and full-term
      SIDS victims. Another developmental change is that IgG levels are lowest when
      SIDS risk peaks, and there is data linking SIDS and infections. Prone position
      may also increase risk. While a developmental model emphasizing neural
      transformation is useful, other factors affect risk also.

PMID- 8275873
TI  - Studies on fetal motor behaviour in normal and complicated pregnancies.
AB  - The possibility of studying fetal motor behaviour by ultrasound techniques has
      provoked research on its potential application for assessment of prenatal
      neurological conditions. The characteristics ('quality') of one particular
      movement pattern, the 'general movement', has been shown to be discriminative
      between uncomplicated pregnancy and major pathology of the developing central
      nervous system. Some recent studies have investigated whether the quality and/or
      the quantity of fetal movements correlated with other clinical variables during
      complicated pregnancies, and whether they provided prognostic information for the
      neurological outcome. Longitudinal research encompassing the pre- and postnatal
      periods was performed on uncomplicated pregnancies and on pregnancies complicated
      by intrauterine growth retardation, oligohydramnios (due to premature rupture of
      the amniotic membranes), or fetal breech position. Although the quantity of both
      fetal general movements and fetal breathing movements were found to be related to
      clinical variables of the fetal condition (such as heart rate variability, heart
      rate decelerations), clinical application seems limited due to large inter- and
      intra-individual variabilities. In contrast, the quality of fetal general
      movements appeared highly correlated with parameters of fetal clinical condition
      in individual cases and fulfilled several prerequisites for serving as a reliable
      diagnostic tool for prediction of the fetal condition and for assessment of the
      integrity of the central nervous system.

PMID- 8275874
TI  - The optimality concept and its clinical value.
AB  - To verify the clinical usefulness of the optimality concept in general and its
      prognostic value for later outcome, all babies born at all 14 maternity hospitals
      in Slovenia in the period from 1987 to 1991 (124,759 newborns) have been
      screened. In order to get an estimate of their condition Prechtl's original list
      of optimality has been adapted to 51 items representing mostly obstetric
      variables. The median of perinatal optimality scores for all newborns was 45 (six
      negative points) in mature, and 41 (10 negative points) in premature infants.
      Girls born at term scored better than mature boys, whereas there was no sex
      difference in the median score in prematures. Analysis of the data has shown that
      the majority of items which were non-optimal and which were associated with the
      greatest number of other non-optimal factors had to do with disturbances in
      oxygen supply. Children who developed cerebral palsy had a lower optimality score
      at birth than the remainder of the newborns. In these children the difference
      between the sexes is even more pronounced, to the advantage of the girls.
      Prematurely born children with spastic diplegia had a lower optimality score than
      mature children with diplegia. The opposite was noticed in children born
      prematurely and at term who developed spastic tetraparesis or dyskinesia. The
      present follow-up study has shown that predictions of disability were most
      accurate in the group of newborns who were clinically at risk at birth and who
      also had a low optimality score. The combination of both appraisals is the best
      way to identify newborns who need special attention.

PMID- 8275875
TI  - Transitory neurological findings in a population of at risk infants.
AB  - Two-hundred fifty infants with high and no risk history transitory neurological
      findings (TNF) were examined during the first year of life. The neurological
      situation and the developmental progress were reconsidered in these children at
      2.5-4.5 and 5-7 years of age. TNF were diagnosed mainly during the first two
      trimesters. Hyperirritability and asymmetries resolved to about 70% during the
      first half of the first year of life. In contrast, isolated central hypotonia
      resolved over a much longer period. No correlations of distinct types of TNF
      could be found with VLBW and LBW-infants, with fullterm infants, with
      birthweights, nor with risk factors. Children who developed spastic CP presented
      permanent hypertonia beside other specific neurological symptoms during the
      second half of the first year of life. Children with lasting non-spastic
      handicaps showed permanent hypotonia combined with other neurological
      abnormalities and symptoms of psychomotor retardation, which evolved also during
      the second half of the first year. From these results the question arises: which
      parts of TNF are essentially neurobiological findings indicating processes of
      transformation of the sensory motor system from non-intentional fetal to
      intentional motor behaviour of early infancy. TNF, then, should not longer be
      looked at as symptoms of pathological value only.

PMID- 8275876
TI  - Developmental features of the brain in preterm and fullterm infants on MR
      imaging.
AB  - Normal development and maturation in pre- and postnatal periods were studied
      using MR imaging. For this purpose, we performed MR imaging at a postmenstrual
      age of 37-44 weeks in both low-risk preterm and fullterm infants and assessed the
      myelination pattern and the dimension of the pituitary gland, corpus callosum,
      pons and cerebellar vermis. There were no differences in stages of myelination
      and the size of these structures in both groups. MR imaging was also performed in
      infants with various cerebral injuries. Focal or diffuse areas of hyperintensity
      on T2-weighted images and delayed myelination were the commonly observed abnormal
      findings in these infants.

PMID- 8275877
TI  - The developmental approach to psychopathology in childhood and adolescence.
AB  - The task of developmental psychopathology is to integrate biological processes of
      maturation with psychological interactions and social influences. Attempts to
      explain behavioural maladaptation during childhood therefore require multi-level
      models. Examples are given in which structural lesions are obvious (fetal alcohol
      syndrome) or less clear (learning disabilities) and in which the expression of
      psychopathology varies with development. Recent work suggest adult schizophrenia
      to be related to prenatal neuropathology, thereby opening new perspectives for
      developmental studies.

PMID- 8275878
TI  - Neurobehavioural relationships in children: new facts, new fictions.
AB  - An overview is given of recent research developments with respect to the two main
      derivates of MBD, namely ADHD and clumsiness. Some conceptual and methodological
      issues of longitudinal and cross-sectional studies on early risk for
      neurobehavioural disorders are discussed.

PMID- 8275879
TI  - Heart rate variation during fetal behavioural states 1 and 2.
AB  - Fetal heart rate (FHR) variation was numerically assessed in relation to
      behavioural states in 34 normal near term fetuses, in order to study the normal
      ranges of FHR variation during state 1F and 2F and to determine possible factors
      influencing variation in these states. In all individuals 2-h recordings were
      made of fetal heart rate, and body and eye movements. FHR variation was
      quantified using the Sonicaid System 8000. During both 1F and 2F there was a
      large range in variation, with a wide overlap in variation between both states
      (mean 1-min range in pulse intervals 16-53 ms and 36-97 ms, respectively). In all
      fetuses variation was higher during 2F than during 1F. The large ranges in
      variation were mainly caused by differences in basal heart rate and the
      correlation coefficients between rate (beats/min) and variation were -0.68 and 
      0.49 for 1F and 2F, respectively. Other reasons for a relatively high FHR
      variation during 1F included 'pseudo' sinusoidal patterns related to fetal
      sucking or mouth movements and relatively flat periods sporadically interrupted
      by an acceleration. With the System 8000, periods of low and high variation are
      identified using fixed criteria. Because of the large overlap in variation
      between both states, these episodes poorly correlated with the underlying
      behavioural states. Objective identification of the heart rate patterns during
      states 1F and 2F requires incorporation of heart rate itself in the analysis. As
      yet, 'global' visual identification of heart rate patterns is superior to
      computer analysis in identifying the underlying fetal behavioural states.

PMID- 8275880
TI  - General movements in early infancy: what do they tell us about the nervous
      system?
AB  - Developmental changes in muscle coordination patterns of normal and abnormal
      general movements (GMs) are described. GMs were studied simultaneously with video
      recording and polymyography (polyEMG). GMs of normal full-term infants gradually
      lose their neonatally slow and 'writhing' character, to be turned into the
      elegant flow of small movements of 'fidgety' GMs at the age of 2-3 months. This
      transformation coincides with changes in the polyEMG. Tonic background activity
      decreases concurrent with a reduction in amplitude and duration of phasic bursts.
      The coordination between antagonistic muscles does not change, co-activation
      remains the prevailing pattern. Secondly, preliminary results on healthy preterms
      (n = 6) are presented. At the examination age of 33-34 weeks postmenstrual age
      the preterms showed so-called 'preterm' GMs, which are characterized by variation
      and graceful complexity. EMG burst duration was significantly longer during
      'preterm' GMs than during 'writhing' GMs of full-term newborns. The percentage of
      co-activation during 'preterm' GMs varied considerably. The polyEMG of 'writhing'
      GMs of two preterms, who were followed longitudinally, differed from that of
      'writhing' GMs of full-terms. At 'fidgety' age the EMG differences between
      preterms and full-terms had disappeared. Finally the first results on abnormal
      GMs are reported. A synchronized onset of muscle activity in all extremity
      muscles and 'packaging' of EMG-bursts into subunits of 5-8 Hz. seemed to be
      specific properties of these abnormal GMs. This could indicate a loss of
      supraspinal control.

PMID- 8275881
TI  - Differential effects of brain lesions and systemic disease on the quality of
      general movements: a preliminary report.
AB  - Assessment of the quality of general movements in preterm infants by means of 1-h
      video recordings is a sensitive method for investigating the integrity of the
      central nervous system. In two preterm infants, who were followed weekly until
      term, an abnormal quality of general movements was found, presumably due to
      systemic disease (bacterial and fungal infections). Both children were
      neurologically normal at the age of 6 (case A) and 12 months (case B) corrected
      age. In contrast to abnormal general movements due to a brain lesion, the
      abnormal quality of general movements in systemic disease is not consistently
      observable, not even during the 1 h of video recording. The presence, in
      otherwise abnormal general movements, of remaining rotations, superimposed on
      flexion and extension of the limbs, appears to be a reliable indication for a
      favourable outcome. Another abnormality seen in one of the infants was a severe
      reduction in the number of general movements, but with a normal quality in the
      remaining few general movements. This indicates that a reduction in quantity of
      general movements is prognostically not a bad sign, at least not if the quality
      of the remaining movements is normal. Although the underlying pathophysiologic
      mechanisms remain unclear, these findings are important in clinical practice. It
      means that it is possible to discriminate between abnormal general movements due
      to a cerebral lesion, and abnormal general movements due to systemic disease
      (infection), provided that the observation period is sufficiently long and a
      longitudinal developmental trajectory is obtained.

PMID- 8275882
TI  - Neurological development during toddling age in normal children and children at
      risk of developmental disorders.
AB  - Toddling age (1.5-4 years) is a period in which the quality rather than the
      quantity of motor functions changes. We examined 305 normal and 43 so called
      'risk' children with an examination technique which concentrates on observations
      of motor functions (grasping, sitting, crawling, standing and walking) in a
      standardized free field situation. Examples of the changes during toddling age
      are presented such as the decrease of yoke movements (i.e. shoulder movements
      during reaching), the increase of trunk motility, of variability of speed during
      crawling, narrowing of gait width, and an increased ability to avoid objects on
      the floor and to show maneuverability during walking. All changes occurred in the
      normal children between the ages of 2 and 3 years. They reflect a
      'transformation' of neural functions. Many of the 'risk' children show
      qualitatively different motor behaviour, which is interpreted as non-optimal and
      which can be an early sign of neurological impairment. The transformation in
      neural functions is discussed in terms of neuroanatomical changes during toddling
      age.

PMID- 8275883
TI  - Neurobehavioral relationships and puberty: another transformation?
AB  - In a follow-up study of the Groningen Perinatal Project (GPP) on minor
      neurological dysfunction (MND) at 12 and 14 years the onset of puberty appeared
      to play a role. The children were selected on the presence (n = 185) and absence
      (n = 185) of MND at 9 years. Puberty was defined by the presence of three or more
      physical puberty signs. With the onset of puberty the incidence of MND decreased.
      The neurobehavioral relationships became more explicit after the onset of
      puberty. All types of MND were related to behavioural and cognitive problems at
      this developmental stage. In normal children, boys showed an increase of strength
      during puberty whereas the movements of girls became more fluent. The apparent
      changes in neurological function during puberty were interpreted as a
      transformation of the central nervous system. The possible causes are discussed.
      The conclusion is that gonadal hormones and especially oestrogens, play a role.
      The fact that two-thirds of the children with MND and behavioural problems
      outgrow the problems during puberty, can be of great help. Finally, any
      longitudinal study of brain function, which includes the age of puberty, should
      pay attention to the pubescent stage.

PMID- 8275884
TI  - Information processing in children with minor neurological dysfunction:
      behavioural and neurophysiological indices.
AB  - Minor neurological dysfunction (MND) refers to deviant function of the central
      nervous system in the absence of localizable neurological disorders. Children
      with no signs (n = 28) and with varying grades of MND (n = 48), classified
      according to failure on circumscript neurological subsystems, were administered
      selective and sustained attention tasks at the age of twelve. During the
      execution of one of the tasks, electrocortical activity of the brain was recorded
      at the Fz, Cz, Pz and Oz scalp locations. Of main interest were behavioural and
      electrophysiological indices of deficits in attentional control. With respect to
      the latter category, the investigation was focused on differences in event
      related potential amplitudes reflecting subprocesses of cognitive processing
      (processing negativity, P300). Following a linear stage model of information
      processing, it was found that children who failed on three or more neurological
      subsystems (in particular on fine manipulation and coordination), exhibited
      deficits in the encoding, search and decision stages of processing. Furthermore,
      the children with MND showed a reduced positive parietal shift on target
      presentation. Under complex task conditions, children without MND showed a
      decrease in P300 amplitude which reflects the impact of processing negativity as
      a result of increased task demands; this effect was absent in children with MND.
      These electrocortical differences suggest imbalances in the external and internal
      neural regulation of the flow of information in the brain.

PMID- 8275885
TI  - Consequences of cerebellar lesions at early and later ages: clinical relevance of
      animal experiments.
AB  - Animal experiments demonstrated that reactions of the brain after early lesions
      differ from those after lesions at adult age. Detailed knowledge on the
      neuroanatomical and neurophysiological consequences of brain lesions was obtained
      in humans and will be gained from lesion experiments in animals. Prerequisites
      for extrapolating animal data to the clinical situation are discussed: knowledge
      on the maturational stage at which the lesion occurs and the behavioral
      expression of the damaged neural system. The extensive remodelling after early
      unilateral cerebellar hemispherectomy and its consequences for behavioural
      development in the rat are presented and discussed.

PMID- 8275886
TI  - Development of locomotion in the rat: the significance of early movements.
AB  - The development of the nervous system is determined by an interaction between
      genetic and epigenetic factors. We investigated the possible role of
      proprioceptive afferent input in the development of locomotion in the rat.
      Kinematic analysis of locomotion in normal rats reveals a marked transition from
      immature overground locomotion into the adult pattern around the 15th postnatal
      day. Around this age, the timing of EMG activity in the tibialis anterior and the
      gastrocnemius muscle in the hindpaw gains accuracy and the intensity of the EMG
      increases. In the soleus muscle we observed an increased regularity in the shape
      of individual motor unit potentials. Neuroanatomical research revealed the
      occurrence of dendrite bundles in the motoneuronal pool of the soleus muscle pool
      from the 16th day as the result of a reorganisation. Immobilisation of one
      hindlimb in an extended position by casts around the leg from the first till the
      20th postnatal day does not interfere with the development of dendrite bundles in
      the soleus motoneuronal pool. However, we demonstrated long lasting abnormalities
      in the timing of the EMG activation patterns in the gastrocnemius and the
      tibialis anterior muscles. It is conceivable that the experimental interference
      with afferent feed back is the causative factor of these functional
      abnormalities.

PMID- 8275887
TI  - [Study of the remission period (between crises) of unipolar and bipolar manic
      depressive disorders. Personal study of 95 patients].
AB  - The personality abnormalities observed during unipolar and bipolar manic
      depressive disorders are known for years by german psychiatry as depressive
      temperament. In USA many works based on DSM III criteria have studied personality
      abnormalities coexisting with depression. The most frequently abnormalities are
      dependent, avoidant, compulsive, border line personality, observed with a
      frequency of 48% (P.A. Pilkonis) to 74% of patients (T.M. Shea et al.). But the
      personality traits or disorders are not the disorders only observed during
      remissions and intercrisis. Our personal work have studied the other disorders.
      This work concern pre-morbid period and intercrisis of 95 manic-depressed
      patients (45 unipolar and 50 bipolar patients). The time of remission is at least
      three months. Remission is certified by maximum scores of 10 on MADRS, 12 on Bech
      Rafaelsen scale. The study of personality traits and other mental disorders is
      based on DSM III-R criteria. It is completed by Hamilton-Anxiety-Scale, Eysenck
      Personality Inventory and Beth-Israel Questionnaire of Sifneos. This study shows
      the following results. In pre-morbid period, the anxiety disorders are
      statistically more frequent in unipolar patients: generalized anxiety (35%),
      panic disorder (27%), psychosomatic disorders (30.5%). During intercrisis, the
      anxiety disorders are statistically more frequent in unipolar patients:
      generalized anxiety (51.1%), agoraphobia (31.1%) obsessive disorders (26.6%),
      panic disorder (18.2%). But this co-morbidity with anxious disorders is highly
      correlated with the incomplete characteristic of remission. During remission the
      personality abnormalities are similar to american studies, more frequent in
      unipolar patients, particularly obsessive personality (22.2 to 4%).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8275888
TI  - [Anticipatory Cognitions Questionnaire (ACQ). Presentation and validation].
AB  - The capacity of anticipation is fundamentally disturbed in depressed patients.
      These patients make negative predictions. Anticipation disturbances are reflected
      in different symptoms but also in the patient's cognitions. The cognitive
      approach is an operational way to deal with the concept of anticipation. The
      cognitive model of depression has been extensively studied and cognitive
      therapies have been validated as effective treatments of depression. A self
      questionnaire has been elaborated, taking into account the different cognitive
      mechanisms disturbed in depressed patients. The "Anticipatory Cognitions
      Questionnaire" (ACQ) explores patient's cognitions in concrete daily life
      situations that require anticipation. The first version of this questionnaire
      contained 18 items. A previous study had led to reduce the number of items and to
      modify the form of the questionnaire. In its final version, the ACQ has 8 items.
      Each of them refers to a concrete situation (i.e. "I have no news from a loved
      one") and the patient is asked to say how a proposed cognition (i.e. "I will call
      him to get in touch") applies to him, choosing one of the four answers "true",
      "rather true", "rather wrong" and "wrong". The validation of this questionnaire
      has been carried out, in comparison with the MADRS and Pichot's QD2A. 151
      subjects were included in this validation study, 72% of them meeting with the DSM
      III-R diagnostic criteria of clinical depression and 28% not having any
      psychiatric disorder. Statistical analysis shows that the ACQ is more sensible
      than the QD2A but less than the MADRS.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275889
TI  - [Translation and application of the Simpson and Angus Scale of Extrapyramidal
      Symptoms].
AB  - Extrapyramidal side effects of neuroleptics are important in clinical practice.
      Study of extra-pyramidal side effects is also of importance for researchers who
      test new antipsychotic agents or study tardive dyskinesia. A french translation
      of the Simpson-Angus Rating Scale of extra-pyramidal side effects thus appeared
      useful. This scale contains 10 items: Gait, Arm dropping, Shoulder shaking. Elbow
      rigidity, Wrist rigidity, Leg pendulousness, Head dropping, Glabella Tap, Tremor,
      Salivation. Each item is rated between 0 and 4. A total score is obtained by
      adding the items and dividing by 10. Scores of up to 0.3 are considered within
      the normal range. The scale original has been validated in a population of
      fourteen psychotic inpatients taking, in a double-blind procedure, placebo,
      haloperidol 6 mg/day or haloperidol 30 mg/day. Patients receiving haloperidol 30
      mg/day presented more extrapyramidal symptoms than patients under placebo. The
      Simpson Angus rating scale has also been shown to have clinical validity and high
      inter-rater reliability. It can be routinely used in clinical drug evaluation.
      The french version was used in a population of 30 psychotic inpatients fulfilling
      the DSM III-R criteria of schizophrenic disorder. Patients were treated for at
      least two weeks, orally, either with a phenothiazine (chlorpromazine 350 mg) or a
      butyrophenone (haloperidol 15 mg). 10 of the 30 patients received, in addition,
      anticholinergic agents (trihexiphenidyl, 5 mg). The french version of The Simpson
      Angus Rating Scale appeared to be easy to use and not time-consuming. Interraters
      correlation was high. Patients receiving butyrophenones or phenothiazines had no
      significantly different ages and sociodemographic characteristics.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8275890
TI  - [Mortality and cause of death in schizophrenia. Review of the literature].
AB  - Through a review of the literature, the average mortality in schizophrenia is
      twice higher than among the population. This over mortality is highest among the
      20-40 years range of age and added risk tends to disappear after 60 years. All
      studies stress the unnatural causes of death, suicide or accidental deaths.
      However several studies found an over mortality caused by natural death. The
      pathologies most often involved are: infections, lung, gastrointestinal,
      urogenital and cardiovascular diseases. Cancer mortality in schizophrenic
      patients is still debated. Some studies point out a reduced mortality compared to
      the general population whereas other studies find similar or over mortality.
      Nevertheless mortality ratio is found to be near 1 in the majority of studies. So
      it can be admitted that schizophrenic patient do really not differ from the
      general population in regard to cancer mortality. Premature death is highly
      linked to suicide. The epidemiological indicators that enable us to estimate the
      importance of suicide mortality are: the rate of suicide per 105 patients per
      year varies between 150 and 500, the percentage of death by suicide range between
      10 and 15 percent. Suicide risk factors are numerous. Some of them are accepted
      as valid and others are still discussed. The former are: male gender, young and
      medium age ten first years of the illness course, associated depressive symptoms,
      past history of suicide attempts, iterative relapses and post hospital discharge
      period. The latter are: social isolation, celibacy, unemployment, high level of
      instruction, delusional and hallucinatory activity and familiar rejection.

PMID- 8275891
TI  - [Value of NMR spectroscopy in exploring the cerebral metabolism of patients
      affected by Alzheimer's disease].
AB  - Besides imaging NMR can obtain spectrum reflecting brain tissues components able
      to resound. Some of these take an active part in a CNS metabolism: such are H (in
      water) and P (in MPA-TPA, etc.). This new investigating method already showed
      interest in vitro (tissues cultures) and in vivo (muscular metabolism) studies.
      Its application to cerebral metabolism studies are going to spread thanks to
      technological advances (magnetic field more powerful: air gap broad enough for
      human head passage). The first results of this investigation, in 5 SDAT patients
      diagnosed with respectively international inclusion criteria (NINCDS-ADRDA) and
      exclusion ones (such as XR Scan and SPECT exploration), are presented; they are
      divided into two different groups showing PME (phosphomonoesters) peak dropped to
      3.2 or 1.8 in one part, and raised to 15.5 till 27 ppm (parts by million:
      conventional unit dealing with substances concentration) as the normal range is
      set at about 7 +/- 4.5 ppm. Such PME changes have showed in an other B. Roussel's
      study to be a good biological index correlated with the age and the CNS state;
      these results seem to be of interest, mainly (that must be emphasized) as this
      technique is quite non intrusive and non irradiating.

PMID- 8275892
TI  - [Hypothetical model of serotonin deficit in the aged subject. Development and
      validation of a clinical scale].
AB  - Few works exist about specific abnormalities of neurotransmission, therefore
      noticeable and with important clinical consequences in elderly patients.
      Specially serotonin, which neurotransmission is lower, seems to have a wide
      influence. The symptomatology of the serotonin shortage is well known in the
      young adult (Asberg and Van Praag). The aim of this study is to apply those
      hypothesis and to look for a particular clinical expression of symptoms usually
      related to a low level of serotonin in an older population, and this in a
      transnosographic way. We built up a clinical scale gathering different symptoms
      supposed to be related to a defect in the serotonin transmission in elderly
      subjects. From a first factor analysis, a dimensional scale of ten items as been
      settled and validated in 75 inpatients over 60 years old; each patient has also
      been assessed by a series of tests (MMS of Folstein, Hamilton Depression Rating
      Scale, Jouvent mood scale, Widlocher Retardation Scale). Factor analysis results
      show an homogeneous factorial structure and highly selective items and had a
      three factors dispatching (a "main" factor, a "depression" factor, and "sleep"
      factor). Those subgroups of symptoms have a clinical meaning and fit the
      litterature. We also find a good specificity: the factor analysis on added items
      of depressive semiology (Hamilton scale) and serotonin related semiology shows
      the splitting of the Hamilton items, whenever the 5-HT- Scale items keep a steady
      factorial repartition. Those preliminary results deserve further studies; and
      external validation of the scale remains to be done. Nevertheless, the structure
      of this scale shows a beginning of internal validation and seems to be
      interesting in the elderly clinical evaluation.

PMID- 8275893
TI  - [Specifics of cognitive behavioral therapy in schizophrenia. Integrated program
      of psychological therapy].
AB  - According to the authors, information processing disorders contribute essentially
      to the vulnerability of the schizophrenic patient. Attentional/perceptual and
      cognitive disorders exert a pervasive influence on more complex levels of overt
      behavior in schizophrenia. Conversely, behavioral deficits influence cognitive
      functioning as well. Psychosocial rehabilitation of patients with schizophrenia
      must therefore address the impact of disordered attentional/perceptual and
      conceptual processes and their integrating organization on behavior as well as
      the effects of behavioral dysfunctions on cognition. The Integrated Psychological
      Treatment Program (IPT) for schizophrenic patients provides means of addressing
      these interactions. The designation "integrated" implies that the treatment is
      directed at cognitive disorders as well as behavioral/social deficits by using
      highly structured interventions, and is carried out with "reality-oriented"
      material. This treatment approach has been developed by Brenner and al., since
      1976. The original IPT includes five subprograms: Cognitive Differentiation,
      Social Perception, Verbal Communication, Social Skills and Interpersonal Problem
      Solving. Patients first work on improving disordered basic cognitive functions in
      the Cognitive Differentiation subprogram. Exercises are directed at impairments
      in attentional/perceptual and conceptual processes. Mastery of this subprogram
      leads to the Social Perception subprogram, which aims at disturbances in
      processes of stimulus discrimination and interpretation on perceiving and
      assessing social interactions. The Verbal Communication subprogram follows
      successful completion of the previous subprograms and trains associative-semantic
      processes as well as basic skills necessary for conversation. In the Social
      Skills subprogram, interpersonal behaviors and self-instructions required for
      gaining instrumental and emotional aims are taught.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8275894
TI  - [Fluoxetine and extrapyramidal symptoms. Two case reports].

PMID- 8275895
TI  - [Hyperthymic disorders].
AB  - Hyperthymia, as referring to the book by J. Delay: "les dereglements de l'humeur"
      (1946), means from a clinical point of view, an exaggeration of the level of
      mood, as well on the one hand, expansive and joyful, as, on the other hand,
      distressing, within a withdrawn self. K. Schneider had described an hyperthymic
      personality in 1923: optimist, dynamic, taking initiatives, or more simply
      hypomanic. He opposed this type of personality to depressive personality types.
      Delay unified these two pathologic evolutions within a physiopathological and
      psychopathological unique concept. Conversely, H. Ey denied this unique affective
      conceptualization of the disease. From his physiopathologic jacksonian point of
      view, a certain level of destruction of consciousness explains, solely, both
      affective and noetic disorganization of these so called hyperthymias. Since the
      early eighties, Angst, Akiskal, Cassano, brought up to date the adjective
      hyperthymic. They assessed the correlation between premorbid personality disorder
      and mood disorder: a number of bipolar disorders are linked with premorbid
      hyperthymic disorders. This was the K. Schneider' position who linked traits and
      states, as Kraepelin did for the manic premorbid disposition. Choosing a
      dimensional approach, one question has to be asked: can hyperthymia be found as a
      previous personality trait of different other diseases? An anxious hyperthymia
      can be found linked to some panic attacks and other neurotic symptoms. A
      delusional hyperthymia is described by Janzarik who thinks that delusional ideas
      are linked to a kind of delusional mood. G. Petit, in 1933, subsumed the
      existence of a paranoid hyperthymia within the more general concept of the
      passional psychoses described by de Clerambault, Delmas and Borel.

PMID- 8275896
TI  - [J. Delay hypothymic disorder. Current aspects and pertinence of the concept in
      schizophrenic states].
AB  - In the first part, the authors re-examined the concept of "hypothymie" described
      by J. Delay in 1946. "Hypothymie" is characterized by a mood disorder and
      particularly by an absence of mood and it is a fundamental syndrome of
      hebephrenia. From this syndrome "hypothymie", others signs will appear such as
      schizophrenic symptoms (characterized by attention disorder and formal thought
      disorder), paranoid symptoms or catatonic ones. Several authors, like J. Delay,
      had emphasized the importance of the mood disorder (an absence) in this
      pathology. It is the case of Kretschmer, Dide and Guiraud (who evoked the
      "athymhormie"), Bleuler, Kraepelin and also Stransky, Griesinger and at the
      beginning of the XIXth century, Haslam in England and Pinel in France. In the
      present time, "hypothymie" is related to some current concepts, especially the
      deficit forms of schizophrenia described by Carpenter and the schizophrenia type
      II defined by Crow. In the second part, the relationships between paranoid
      symptoms, depression and "hypothymie" were studied. The authors stressed the fact
      that there is an overlap between depressive and paranoid symptoms at the acute
      phase. They gave an illustration including 51 patients in an acute phase and in a
      stabilized one. In the acute phase, there was a negative correlation between
      positive symptoms and depressive symptoms in particular between conceptual
      disorganization, suspiciousness/persecution, positive formal thought disorder and
      depression (r = -0.65, p < 0.01; r = -0.57, p < 0.01; r = -0.66, p < 0.01
      respectively). These correlations disappeared at discharge of the hospital and
      did not exist in the stabilized group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275897
TI  - [The concept of mood in psychology].
AB  - The concept of mood is complex and difficult to establish. It reflects a moving
      notion that cannot be easily grasped. It has always been a fundamental concept in
      the history of philosophy and medicine. The origin of mood relies on the theory
      of the four humours: blood, phlegma, yellow and black bilious. Mood can be
      balanced by the equilibrium of these four liquids. Mood is also difficult to
      define because one's judgment depends on the perception of mood in other people.
      It is a highly subjective concept which is backed by personal references. Mood
      can be expressed with different tonalities. Its panel of expressions can likely
      explain the different definitions and analysis of this notion. The first part of
      this report tends to clarify the definition of mood regarding emotion, feeling or
      affect. Emotion is an instantaneous perception of a feeling. Affect corresponds
      to a freudian notion of drives. In the second part different conceptions of mood
      in psychology are treated. Some of them have been derived from philosophical
      conceptions of mood e.g. the cognitive theory and ethological conception. Others
      are based on the pathological model of manic depressive psychosis e.g.
      phenomenological and psychoanalytic views of mood theory. Moreover this analysis
      will attempt to show the interest of psychological tests to confirm mood troubles
      or to substantiate a clinical diagnosis of mood disorders. The conception of mood
      in cognitive psychology is derived from the analysis of emotion. Mood is
      considered as a group of persisting feelings associated with evaluative and
      cognitive states which influence all the future evaluations, feelings and
      actions.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275898
TI  - [Unidimensionality of the Yesavage and Brink Geriatric Depression Scale].

PMID- 8275899
TI  - Pharmacological treatment of child and adolescent major depression.
AB  - Controlled studies of the pharmacological treatment of child and adolescent major
      depression have lagged significantly behind adult studies. To date, definitive
      results demonstrating efficacy or the lack thereof for heterocyclic
      antidepressants do not exist for depression during either childhood or
      adolescence. This article reviews the available literature and suggests
      directions for future studies. In addition, the very few non-controlled studies
      of lithium and MAOIs in this population are also discussed.

PMID- 8275900
TI  - [Pharmacologic treatment of obsessive compulsive disorder in the child and
      adolescent].
AB  - Although obsessive compulsive disorder (OCD) was considered as a rare and
      treatment-refractory syndrome, research findings from the past decade have
      focused new interest on the disorder. Epidemiological studies have shown that
      prevalence rate of OCD was much higher than previously thought (1% of the general
      adolescent population), and the discovery of a class of psychiatric drugs
      specific for OCD has brought new therapeutic options as well as
      pathophysiological hypotheses for the disorder. Rigorous treatment studies have
      demonstrated that most OCD patients respond to specific pharmacological
      therapies. The most studied treatment so far has been clomipramine, which
      appeared superior to placebo and to other antidepressant drugs (amitriptyline,
      imipramine, desipramine and clorgyline) in a large number of independent
      controlled studies. In one placebo-controlled study and one study versus
      desipramine, clomipramine administered to children and adolescents aged 6 to 18,
      at mean doses of 141 mg/day and 150 mg/day respectively, was well tolerated and
      had a significant anti-obsessional effect. The novel antidepressant drugs
      fluvoxamine and fluoxetine are currently under investigation for the treatment of
      OCD, especially in children. First results indicate a clinical efficacy similar
      to that of clomipramine, with lower incidence of side-effects. The few drugs that
      have been demonstrated to be anti-obsessional share a high potency for the
      blockade of serotonin reuptake. A serotonergic mechanism has therefore been
      proposed for anti-obsessional drug action and further strengthened by studies
      demonstrating correlations between clinical response and changes in several
      serotonergic markers with clomipramine treatment.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8275901
TI  - [Indications for clonidine in child psychiatry].
AB  - The two principal indications of clonidine in child psychiatry are the "attention
      deficit hyperactivity disorder" (ADHD) and Tourette's disorder. In the first case
      (ADHD), clonidine (4 to 5 micrograms/kg/day) is efficient (25 to 50% of
      improvement) with minimal untoward effects. The comparison between clonidine and
      methylphenidate (MPH) in this disease showed different actions of these two drugs
      on target symptoms: MPH preferentially acts in children with major attention
      deficit and moderate hyperactivity whereas clonidine is more advocated in ADHD
      children with hyperarousal, hyperactivity and aggressivity symptoms. In
      Tourette's disorder, clonidine improves 30-50% of cases. Many studies have
      compared the efficiency of clonidine, neuroleptics and clonazepam. Clonidine is
      less efficient than neuroleptics such as haloperidol or fluphenazine but it is
      more efficient than clonazepam. Clonidine seems to be a good alternative to
      neuroleptics when these are not tolerated. Some authors recommend the association
      clonidine-clonazepam. Clonidine is very useful in Tourette's disorder associated
      with other syndromes such as obsessive-compulsive disorder, ADHD or withdrawal
      symptoms of neuroleptics. In contrast, clonidine has to be avoided in a
      depressive child. Clonidine in other psychiatric disorders such as infantile
      psychosis with hyperactivity, bipolar disorder, panic disorder, aggressivity and
      post-traumatic stress disorder has not been studied in children, but could be
      worth investigating.

PMID- 8275902
TI  - Clinical efficacy of methylphenidate in children and adolescents.
AB  - The efficacy of methylphenidate (MTP) is amply documented for children with ADHD.
      In addition to modifying the central features of the disorder, inattention,
      impulsive behavior and excessive motor activity, the medication has been shown
      also to improve social behavior with peers and adults, as well as academic
      performance. The concerns that these benefits may not extend beyond the period of
      active intervention, and that treatment efficacy in only partial in some
      children, has led to the development of other, psychosocial interventions.
      Behavioral treatment by itself is ineffective, but contributes significantly to
      clinical change in children who derive incomplete gains from MTP alone. Cognitive
      training has not been shown to have therapeutic impact either as a single
      treatment, or as an adjunct to MTP. Clinical indications for MTP extend to
      children and adolescents with Conduct disorders. Treatment affects antisocial
      behavior regardless of the concurrent presence of hyperactivity symptomatology.
      Extended treatment with MTP alone is difficult to implement in older children due
      to lack of cooperation. MTP has been shown to be safe. Deceleration of growth
      velocity is the only identified long-term side effect. It occurs after more than
      one year of treatment at greater than low doses. It appears completely reversible
      with treatment cessation prior to the adolescent growth spurt. Efficacy in
      Attention Deficit-Hyperactivity Disorder (ADHD) is especially well demonstrated
      in preadolescents, with only sparse evidence for efficacy in adolescents.

PMID- 8275904
TI  - [Biological factors in psychological change, or psychological factors between the
      impossible and the prohibited].

PMID- 8275903
TI  - [Opiate hypothesis in infantile autism? Therapeutic trials with naltrexone].
AB  - The opioid hypothesis suggests that childhood autism may result from excessive
      brain opioid activity during neonatal period which may constitutionally inhibit
      social motivation, yielding autistic isolation and aloofness (Panksepp, 1979).
      This hypothesis has now received strong support and is currently based on three
      types of arguments: (1) similarity between autistic symptomatology and abnormal
      behaviors induced in young animals by injections of exogenous opioids, such as
      increasing social aloofness and decreasing social vocalization; (2) direct
      biochemical evidence of abnormalities of peripheral endogenous opioids being
      reported in autism and (3) therapeutic effects of the long lasting opioid
      receptor blocking agent naltrexone in autism. In this article, we give
      description of open and double-blind studies of naltrexone in autism. Naltrexone
      has been tested in several open studies. We performed an open trial with
      naltrexone in 2 autistic girls, displaying serious self-injurious behavior,
      reduced crying and a marked preference for salty and spicy foods, symptoms that
      could be related to a dysfunction of the opioid system. With dosages of 1
      mg/kg/day, we observed an immediate reduction of hyperactivity, self-injurious
      behavior and aggressiveness, while attention improved. In addition, social
      behaviors, smiling, social seeking behaviors and play interactions increased
      (Leboyer, Bouvard et Dugas, 1988). Campbell et al. (1988) has also reported a
      tranquilizing and a stimulating effect in 6 out of 8 children with autism. We did
      confirm these preliminary results in a double-blind study performed on 4 children
      with autism. In a cross-over double-blind study, three dosages of naltrexone
      (0.5, 1 and 2 mg/kg/day) and placebo were compared.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8275905
TI  - [Regulation of the dopamine D2 receptor gene and the early genes in the CNS by
      neuroleptics].
AB  - The interaction of a ligand with its cognate receptor not only activates signal
      transduction pathways but also determines adaptive responses affecting key
      elements in these pathways, in particular the cell surface receptor. Such is the
      case for G protein-linked receptors, the expression and functional status of
      which are highly regulated. The regulatory mechanisms involved can be divided
      according to two distinct time frames, acute and chronic. In the short-term,
      posttranslational mechanisms alter the functional status of the elements without
      changing steady-state levels or gene expression. Protein phosphorylation plays a
      prominent role in these acute adaptive responses. Thus agonists promote
      phosphorylation and the desensitization of several G protein-linked receptors.
      And we have shown in the case of the dopamine D2 receptor that protein kinase C
      modulates receptor coupling to its G-protein. Longer-term regulation involves
      transcriptional (gene expression), posttranslational (mRNA stability), and
      posttranslational (protein phosphorylation) regulation of the turnover of the
      elements in the information transduction pathway. In the case of G protein-linked
      receptors, long-term regulation is often reflected in changes in steady-state
      levels of mRNA (which can be quantified by techniques such as northern blot
      analysis, solution hybridization or in-situ hybridization). For dopamine D2
      receptors, prolonged administration of neuroleptic drugs induces an up-regulation
      of receptor mRNA in various brain regions, probably through an increase in gene
      transcription. Receptor-transduced extracellular stimuli are converted into long
      term changes in gene expression through specific nuclear transcription
      factors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275906
TI  - [Fundamental aspects of molecular biology. The multigene family of 5-HT1
      receptors].
AB  - Genes, constituted by the deoxyribonucleic acid (DNA) contain all the genetic
      information of a cell. DNA is a double helix consisting of two antiparallel
      polynucleotide chains where each nucleotide is composed of the association
      between a base, a sugar and a phosphate group. The chains are associated by
      hydrogen bonds between the bases. Guanine bonds specifically with cytosine while
      adenine bonds specifically with thymine. The sequence of DNA is related to the
      sequence of protein by the genetic code. Each aminoacid is represented by a codon
      that consists of a nucleotide triplet. Information is expressed by a two-step
      process. The first step, transcription generates a single-stranded ribonucleic
      acid called messenger RNA (mRNA) (where a uracil base is present instead of a
      thymine) which acts as an intermediate molecule. In this step, RNA splicing is
      one of the maturation processes consisting of joining the exons by removing the
      introns of the precursor RNA molecule. The second step, translation, converts the
      nucleotide sequence into the sequence of aminoacids. Since the 1970s, the
      progress in DNA technology consisting of the development of molecular cloning,
      DNA library construction and sequencing methods, has made it possible to isolate
      and analyze specific genes directly from the genome. A sequence of genomic or
      complementary DNA (cDNA) is cloned by inserting it into a vector (plasmid or
      phage) that can replicate independently in bacteria. Before cloning, genomic DNA
      is digested into fragments by restriction enzymes (endonucleases cleaving
      specific sequences within double-stranded DNA) whereas RNA sequences are copied
      into cDNA by reverse transcriptase.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275907
TI  - [The P 300 potential in schizophrenia].
AB  - The P3 component of the event-related potential (E.R.P.) is an endogenous
      positive wave with a latency of approximately 300 msec, which is typically
      elicited by rare target stimuli in a detection task. The P3 has been applied to
      the study of cognitive impairments. One of the most consistently replicated
      biologic observation in schizophrenia is the P3 amplitude reduction. More
      recently, a prolonged P 3 latency has been observed by some authors.
      Nevertheless, when the heterogeneity of the schizophrenic syndrome is taken into
      consideration, results reported in the literature do not show much agreement. In
      the present study, we attempted to explore the P 3 component in a group of
      schizophrenic patients with a precisely defined clinical symptomatology. METHODS:
      Subjects. The study included 19 inpatients and 19 healthy control subjects age
      and sex-matched. Patients were medication-free for at least 15 days prior
      recording. According to the DSM III-R diagnosis criteria, 10 patients were
      classified as "paranoid subtype" and 9 as "disorganized subtype". Furthermore, on
      the day of the neurophysiological examination, the patients were interviewed
      using the Scale of the Assessment of Positive Symptoms (S.A. P.S.) and the Scale
      of the Assessment of Negative Symptoms (S.A.N.S.). The median age (SD) of the
      patients was 35.3 +/- 8 years, with a median duration of illness 12.5 +/- 7.2
      years, a median duration of hospitalization 4.2 +/- 4.3 years and a median IQ
      82.8 +/- 13.7. E.R.P. Recording. Subjects performed a two-tone auditory
      discrimination task: they were instructed to count silently infrequent high
      pitched tones of 2000 Hz randomly presented within a serie of low-pitched tones
      of 1000 Hz. E.R.P. were recorded from 16 scalp electrodes (international 10-20
      system) referred to nose. The P 3 was defined as the most positive wave between
      250 and 500 msec after the stimulus onset. The amplitude was measured referred to
      the prestimulus baseline; the latency was measured at the point of maximum
      amplitude. Statistical analysis. The data were submited to a statistical analysis
      (ANOVA, Student's t-test, Fisher PLSD and Scheffe F-test, Spearman's correlation
      and linear regression analysis). RESULTS: 1) The schizophrenic group (N = 19)
      showed both a significantly prolonged latency and a reduced amplitude, compared
      to the control group (p < 0.01). 2) In the paranoid subgroup (N = 10), P 3
      response was later and smaller than in the control group (p < 0.05). The P 3
      latency and amplitude were not significantly different between the two groups of
      disorganized schizophrenics and controls. 3) A significant correlation between
      the global score of the S.A.P.S. and the P 3 amplitude was found (r = -0.67).
      There was no significant correlation between the P 3 parameters and a) the global
      score of the S.A.N.S. and b) the different items of each evaluation scale. 4) The
      P 3 amplitude showed a trend toward a negative correlation with the duration of
      hospitalization. 5) The duration of hospitalization was more important and the
      global score of the S.A.P.S. was higher in the paranoid than in the disorganized
      subgroup. There were no significant differences concerning the global score of
      the S.A. N.S., age, duration of illness, duration of hospitalization, IQ and
      performances in the detection task between the two subgroups of patients.
      DISCUSSION: We confirmed the P 3 parameters modifications in schizophrenic
      patients. The P 3 reduced amplitude and prolonged latency only in the paranoid
      subgroup, while the disorganized subgroup had both values comparable to those of
      the controls, is the main finding in our study. Kutcher or Louza studies tend to
      the same results. Furthermore, we showed that task performances or clinical
      measures such as age, duration of illness, duration of hospitalization or IQ did
      not account as biases of P 3 parameters. These results could be a further
      indication that different subtypes of schizophrenia may have different biological
      substrates.

PMID- 8275908
TI  - [Negative schizophrenic symptomatology and the P 300 potential].
AB  - We studied the latency and amplitude of the P 300 wave of event-related
      potentials (P 3) in 19 hospitalised schizophrenic patients. We used an odd ball
      paradigm procedure in acoustic stimulation. We found a negative correlation
      between the amplitude of P 3 and negative schizophrenic symptomatology, measured
      by the negative BPRS score and the SANS score. However, no link would appear to
      exist in our study between positive symptomatology and P 3 amplitude. The
      correlation with the negative BPRS score is found in both evaluations, at the
      beginning and at the end of the period of hospitalisation. P 3 latency would
      appear to be independent of either positive or negative schizophrenic
      symptomatology. It would thus appear to us that the negative symptomatology,
      rather than the positive, could be at the origin of marked changes in P 3,
      observable fro relatively simple experimental but parameters such as reaction
      time or error scores remain to be specified, even if they appear to intervene
      infrequently. The use of event-related potentials would thus appear pertinent in
      clinical research and could help in the homogenisation of schizophrenic
      populations studied.

PMID- 8275909
TI  - [The basal forebrain. Neuroanato-physiology and neurologic applications].
AB  - The Basal Forebrain region comprises the heterogeneous set of telencephalic
      structures on the medial and ventral aspects of the cerebral hemisphere. Basal
      Forebrain structures include the septal areas, olfactory tubercule, substantia
      innominata, and parts of the amygdala. The basal forebrain region is the site of
      a system of cholinergic neurons projecting to the entire cortical surface. The
      Basal Forebrain is a site of convergence of sleep and thermoregulatory functions.
      Portions of the basal forebrain play prominent roles in the control of the body
      temperature. The medial preoptic/anterior hypothalamic areas have both
      thermosensiting and thermointegrating functions. Cholinergic neurons intrinsic to
      the Basal Forebrain play a fundamental role in sleep onset and maintenance.
      Neurons of the nucleus basalis of Meynert undergo a profound degeneration in
      patients with Alzheimer's disease and provide a pathological substrate of the
      cholinergic deficiency in their brain. Behavior changes and amnesic syndrome may
      complicate surgery for ruptured anterior communicating artery aneurysms.
      Disruption of the blood supply through the perforating branches of the anterior
      communicating artery may probably cause the amnesic syndrome.

PMID- 8275910
TI  - [Self-evaluation of obsessive-compulsive disorder. Adaptation and validation of
      two psychometric scales to the French version].
AB  - Reliable and valid measures of obsessive-compulsive behaviors are essential to
      investigation of obsessive-compulsive disorder (OCD). With observer-rated scales,
      accurate self-assessment is also required in the evaluation of OCD. In a
      collaborative study, two psychometric instruments for self assessment of OCD were
      translated and adapted into a french version: The Maudsley Obsessive-Compulsive
      Inventory (MOCI). and the Lynfield Obsessional-Compulsive Questionnaire (LOCQ)
      with 2 scores generated for "resistance" (LOCQ-R) and "interference" (LOCQ-I).
      The validity and the reliability of these two instruments were studied within
      different selected psychiatric groups, OCD, Panic disorder with or without
      Agoraphobia, Major Depression, and in a control group. Between-groups comparison
      showed that MOCI and LOCQ global scores (respectively 17 +/- 3.9 for MOCI global
      score, p < 0.01; and 40.3 +/- 11.0 for LOCQ-R, 43.1 +/- 12.0 for LOCQ-I global
      scores, p < 0.0001) can differentiate between the obsessional patients and the
      other groups. An overlap between OCD and Major Depression groups was observed on
      MOCI "doubting" and "slowness" sub-scores. By comparing MOCI and LOCQ global
      scores with observer-rated scales of obsessive-compulsive behaviour, we found
      adequate correlations: CPRS-OC (subscale of Comprehensive Psychiatric Rating
      Scale for Obsessions and Compulsions) (r > 0.5; p < 0.01), CAC (Compulsive
      Activities Check-list) (r > 0.6; p < 0.01), and global time spent on rituals (r >
      0.5; p < 0.01). The total MOCI and LOCQ scores were significantly, but weakly
      correlated with depression and anxiety measures (r = 0.30-0.49).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8275912
TI  - [Multicenter double-blind study comparing the efficacy and tolerance of
      paroxetine and clomipramine in reactive depression in the elderly patient].
AB  - This multi-centre, double-blind study, carried out in France, was designed to
      compare the efficacy and tolerability of paroxetine and clomipramine in elderly
      patients, aged 60 or above, with reactive depression according to Feighner's
      criteria. Patients were randomly allocated to treatment with either paroxetine
      (20 mg o.d.), 41 patients, or clomipramine (increasing from 20 mg o.d. to 20 mg
      tds), 42 patients, for 5 weeks. Placebo tablets were used to maintain blinding.
      The degree of depression was determined using the Montgomery-Asberg and the Zung
      self-rating scales, and also assessed on a visual analogue scale. After 5 weeks
      of treatment both treatment groups showed a similar degree of improvement on all
      rating scales. There were no significant differences between the groups. Adverse
      events occurred in 26 and 28 patients in the paroxetine and clomipramine groups,
      respectively. In the paroxetine group, many of the events were typical of the
      gastrointestinal side-effects associated with 5-HT uptake inhibitor therapy.
      Patients receiving clomipramine experienced events of the type commonly reported
      with tricyclic antidepressants. There were no significant differences between the
      groups for either total number of events or for number of patients with specific
      events. Clinical and laboratory monitoring showed that both drugs were well
      tolerated.

PMID- 8275911
TI  - [Value of local cerebral hypoperfusion in the diagnosis of frontal syndromes.
      Importance in medical expert assessment of head injuries].
AB  - The importance of the symptoms linked to a frontal disorder in the intellectual
      and behavioral sequelas of severe cranial trauma, is now measured carefully
      because these troubles are one of the most important obstacle to the social and
      professional come-back. The handicap linked to a disorder of the frontal lobe is
      not well known in all its neurological, mental and sociological dimensions
      because the diagnosis is not easy. To help to this diagnosis, the study of
      cerebral blood flow with SPECT is usefull in medical practice. We present here 4
      clinical cases of post-trauma frontal syndrome not easy to measure. With a
      measure of cerebral blood flow with SPECT, it was observed a decrease of frontal
      blood flow, that allowed to link the neuropsychological symptom to a frontal lobe
      disorder. It seems that in these conditions the post-trauma frontal syndrome is
      not so uncommon.

PMID- 8275913
TI  - [Essay on pain].
AB  - The classical conception of pain, considering it as pertaining to a specific
      sensation, called pain or nociceptive sensation, ie capable of differentiating
      between all informations those which are detrimental to the organism, is
      unsatisfactory. The organization of somesthetic pathways allows to say that this
      pain sensation, associated with temperature sensation, stems from the most
      archaic nervous sensation: that of the most primitive organisms, for whom contact
      provokes a flight reaction. This leads to consider the presence of a "contact"
      sensation, thermic as well as mechanical, "existential" so to speak, far
      different from touch sensation which is a discriminatory sensation. Pain appears
      at one end of a chain, the other end corresponding to cutaneous contacts. These
      latter contacts are pleasurable or very pleasurable, as typified by sexual
      contacts. Beyond pain, the archaic nervous function is the origin of a whole
      defense and protection system for the organism. Pain constitutes the subjective
      alarm mechanism, triggered off in case of lesion or break of the primitive
      envelope or of its by-products. This existential sensation, with pain as its most
      blatant manifestation, has held a central place in the course of evolution: our
      organism could in this way become aware of its own existence. For all of us it
      plays an important role in the organization and structuring of our personality.

PMID- 8275914
TI  - [Hypofrontality and schizophrenia].

PMID- 8275915
TI  - [Epidemiologic research, disorders of eating behavior and addictive behavior].
AB  - The tremendous increase in interest in eating disorders, and especially in
      bulimia nervosa, that has occurred since the last 1970s has resulted in a large
      and contradictory literature about the relationships between eating disorders and
      addictive disorders, especially alcohol and drug abuse. At first sight, according
      to the differences observed between these disorders in most of their
      phenomenological characteristics (age, sex, socio-cultural factors), it may seem
      difficult to draw a parallel between them. However, studies showed that eating
      behavior problems, alcohol and drug abuse nowadays shared some common features in
      adolescents and young people. However that may be, epidemiological studies
      demonstrated a high prevalence of substance abuse among patients with bulimia. In
      anorexia nervosa, this prevalence seemed to be lower. However, significant
      differences have been observed between bulimic and restricting anorexics:
      substance abuse occurred significantly more frequently in bulimic anorexics than
      in restricting anorexics and this characteristic was associated with a higher
      prevalence of impulsive behaviors (i.e. stealing, self-mutilation and suicide
      attempt), laxative or diuretic use and impairments in social relationships. These
      clinical features are quite similar to those observed in bulimic patients with
      substance abuse problems. Follow-up studies also showed that substance abuse
      problems in anorexia nervosa were associated with the occurrence of bulimic
      behaviors. On the other hand, family studies reported that a high prevalence of
      patients with bulimia had at least one first degree relatives with substance
      abuse problems or an affective disorder. In anorexia nervosa, the prevalence of
      substance abuse or depression among the family members seemed to be higher in
      bulimic anorexics than in restricting anorexics.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275916
TI  - [Validation of a French version of the General Health Questionnaire (GHQ-28) in a
      diabetic population].
AB  - The contrast between the great importance of psychiatric disorders and the fact
      that they are often not identified as thus in medical and surgical units has been
      emphasized during the last ten years. The prevalence of depression disorders in
      an hospitalised population of medical patients is generally estimated between 15%
      and 30%. It is admitted that one third to two third of theses cases are not
      diagnosed by non psychiatrist physicians. It is the reason why self
      questionnaires have been finalized in order to detect psychiatric troubles in
      medical populations. The General Health Questionnaire (GHQ), constructed by
      Goldberg, is surely the most internationality used, but no validation study has
      yet been undertaken in France. This study means the validation of a french
      version of GHQ-28 items, set on 46 diabetics (type 1 and type 2) selected in a
      week hospital. This validation is based on the comparison of the two principal
      scoring methods: "GHQ" (0,0,1,1); "CGHQ" (0,1,1,1 for negative items) and the
      determination of the best cut-off score in this specific population. The
      referring DSM III-R diagnoses were assessed by the Composite International
      Diagnostic Interview (CIDI; Robins et al., 1988), which is a highly structured
      psychiatric interview developed by the World Health Organisation. Sixteen
      patients out of the 46 diabetics showed criterions of depressive and/or anxious
      disorders, 6 of them presenting both. The analysis of the answers to the
      questionnaires was based upon the technic of the Relative Operating
      Characteristic (ROC) curves which takes all the sensitivity-specificity couples
      bound to each of the possible threshold-score into account.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8275917
TI  - [Psychometric study in Huntington disease].
AB  - Thirty-two patients suffering from Huntington's disease (HD) were tested with a
      short neuropsychological tests battery in order to make a global evaluation of
      their cognitive functions, and to ascertain whether the tests would be sensitive
      enough, even in the first stages of the disease, and whatever the individual
      neuropsychological profile, to be, possibly, an assessment tool for treatment
      efficacy. Nineteen HD presented with a "mild" form of the disease [stage I and II
      of Shoulson and Fahn (1979)], 7 men and 12 women, with a duration of illness of
      nearly 5 years and 13 HD presented with a "moderate" form (stage III and IV), 5
      men and 8 women, with a duration of illness of nearly 8 years. These 2 groups had
      a comparable age at the assessment time (nearly 47) and did not differ,
      significantly, for the age at onset (39 and 43 respectively), duration of illness
      or psychiatric disorders. Each test result was reduced to its number of standard
      deviations apart the normal mean-value for the same sex, age and study level
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275918
TI  - [Obstetrical complications and schizophrenia. Comparative study of obstetric
      antecedents in schizophrenic and bipolar patients].
AB  - Information on pregnancy and birth complications was recorded for 46 patients
      with DSM III-R schizophrenia or bipolar disorder. The biological mothers of the
      patients were interviewed personally to obtain obstetric information. There were
      no significant differences between schizophrenic and bipolar patients in age at
      the assessment, distribution of sex, paternal social class, age of the mother at
      birth, and birth order. Biological mothers of schizophrenics had more often than
      mothers of bipolar patients an history of miscarriage, but this trend failed to
      reach statistical significance. Pregnancy complications and birth weight were not
      significantly different between schizophrenic and bipolar patients. Birth
      complications were scored according to the method described by Parnas et al.
      (1982). Three scores were obtained for each patient: a frequency score, a
      severity score, and a total score. All the scores were significantly higher in
      the schizophrenic than in the bipolar group (frequency score p < 0.011; severity
      score p < 0.015; total score p < 0.01). Surprisingly, birth complications were
      more severe in female than in male schizophrenics (p < 0.017). The two groups of
      patients could not be differentiated by specific birth complication. The
      schizophrenic patients with a history of birth complication and those without
      such an history did not differ in age at onset, age at first hospitalization,
      family history of schizophrenic or non-affective psychotic disorder, neuroleptic
      resistance, and type of schizophrenia. Because of the small number of subjects in
      each group a type II error cannot be excluded for these negative
      results.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275919
TI  - [Erythrocyte/plasma ratio of lithium. Determination method and individual
      stability].
AB  - Lithium is a very efficient drug for the treatment of maniac-depressive
      psychosis, but its therapeutic index is narrow. Moreover, even with lithium
      plasmatic concentrations in the therapeutic range, some patients showed toxic
      signs when others seemed not to be efficiently treated. The measurement of
      erythrocyte lithium concentration might provide a more rational method than the
      measurement of plasma lithium for monitoring the course of lithium therapy, since
      the mechanisms of lithium transfer across red blood cells resemble those for
      neurons. Toxic effects could then be related to high lithium erythrocyte
      concentrations or a high erythrocyte/plasma lithium ratio (EPR). The
      intracellular lithium concentration depends mainly on the Li(+)-Na+
      countertransport, which is genetically determined. We wondered therefore whether
      the EPR is a specific characteristic of each patient and how long it requires to
      stabilise when lithium therapy is started. The EPR was determined by directly
      measuring the plasma and erythrocyte concentrations with a carefully standardised
      assay (lithium carbonate administered at 7 pm, blood sample taken at 7 am the
      next day). Potassium edetate was preferred as anticoagulant to sodium heparinate,
      which gave an overestimation of EPR. Plasma trapped in the red cell column, with
      polyfructosan as marker, was found to average 4% in our assay conditions
      (centrifugation at 3,200 g, 15 min, 4 degrees C). This standardised assay makes
      it possible to determine the EPR very accurately with an inter-assay variation
      coefficient of about 2.4%. Following the start of lithium therapy, the EPR
      stabilised very quickly, mainly within two days (three out of four patients), at
      a time when lithium erythrocyte and plasma concentrations were still
      increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275920
TI  - [Analgesic effects of a raw extract of Ageratum conyzoides in the rat].
AB  - Ageratum conyzoides (AC) is a plant used in traditional medicine for mental and
      infection diseases, cephalgia, dyspnea, enteralgia and fever. The objective of
      this study is to investigate the antinoceptive properties of Ageratum conyzoides
      in the rat. The raw extract of AC is constituted by a lyophilisated powder
      obtained from leaves juice extract by using a crusher. A dilution of 1% in NaCl
      0.9% is prepared with the lyophilisat. Several doses of this preparation; 25, 50,
      100, 125, 150 mg/kg are injected intraperitonealy in animals. The wistar rats of
      both sexes weighting between 200-250 g are used for this study. Animal's
      behaviour is observed macroscopically; the spontaneous motor activity is measured
      by using Martin et al. method (1990), slightly modified. The number of squares
      crossed by animal is measured every ten minutes during thirty minutes. The rectal
      temperature is sampled and analgesic activity evaluated by the hot plate method
      and by the writhing syndrome induced by acetic acid. AC is compared here with
      morphine 7.5 mg/kg sc and control 0.9% NaCl ip. The student--Fisher t test is
      used for the statistical analysis of the results. The results obtained
      demonstrate that all doses equal or higher than 125 mg/kg cause mortality of rat.
      The doses of 50 and 100 mg/kg are selected for experiments. At these doses, AC
      cause: a precocious ataxia, a sedation and a slight ptosis. Six hours after
      injection, those effects disappear; a reduction of spontaneous motor
      activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275921
TI  - [Randomized double-blind comparative study of the efficacy and tolerance of
      medifoxamine and imipramine in depressed patients].
AB  - Medifoxamine (Cledial TM), a non tricyclic non MAOI antidepressant drug with a
      dopaminergic and serotoninergic mechanism of action, was compared to imipramine
      in a multicenter double blind trial. Patients suffering from DSM III-R major
      depression (without psychotic features), with a minimum inclusion score of 25 at
      the MADRS after an initial 7-day wash-out period, were randomly assigned to a 4
      week treatment by either imipramine or medifoxamine, with flexible doses of at
      least 100 mg after 2 weeks of treatment. No associated treatment was permitted
      except for lorazepam 2 to 5 mg per day. Ninety eight patients were recruited by
      20 centers throughout France. Eighty four terminated the 4-week protocol. Early
      terminations were due to serious adverse events (3), death on imipramine (1),
      protocol violation (1), refusal to continue (1), loss to follow up (1). The 2
      groups of patients were comparable on inclusion. In the medifoxamine group
      (receiving a daily dose of 194 mg at day 28) the percentage of improvement in
      MADRS scores, the number of patients with a MADRS improvement of a least 50% and
      a final MADRS score inferior to 8, were not significantly different from the
      imipramine group (daily dose: 161 mg at day 28). No more difference appeared when
      several clinical variables were analyzed, in particular the DSM III-R
      melancholic, the Newcastle endogenous subtypes and the in or out patient status.
      The two treatment groups were also comparable on other scales (HDRS, HARS
      assessing anxiety, CGI).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275922
TI  - [Double-blind study of mianserin and fluoxetine in ambulatory therapy of
      depressed patients].
AB  - A double blind controlled trial was carried out in 65 depressed out-patients to
      compare the efficacy and tolerance of mianserin with fluoxetine. The two
      compounds present very different pharmacological activities. Mianserin is an
      antagonist of the alpha 2-adrenergic receptors, while fluoxetine is an inhibitor
      of recapture specific to serotonin. Requirements for inclusion were: depressive
      episode of less than 2 months duration, meeting the criteria for one of the sub
      types of depression described in DSM III, with a minimum score of 25 on the
      Montgomery Asberg Depressive Rating Scale (MADRS). The patient's ages ranged from
      18 to 65. The only psychotropic medication allowed in association to the
      treatment was prazepam (up to 40 mg/day). Patients gave their written consent to
      the study. Assessment, using the Montgomery Asberg Depression Rating Scale
      (MADRS), the HARD diagram, the check list for somatic symptoms and side-effects
      was carried out before treatment and at the end of weeks 2, 4, 8. Assessment of
      anxiety using the Hamilton Anxiety Rating Scale (HARS) and of sleep disturbances
      using a sleep questionnaire was carried out before treatment and at week 4. The 8
      items of the sleep questionnaire covers the complaints listed in criteria for
      insomnia disorders (307.42 DSM III-R). Clinical Global Impression (CGI),
      Therapeutic Index (TI), Tolerance Global Impression were assessed at end-point.
      The 2 groups were strictly comparable in respect to the clinical status at base
      line (diagnosis, history and duration of the depressive illness, MADRS and HARD
      diagram scores).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275923
TI  - [Subsequent manic onset caused by association of vigabatrin-clomipramine].

PMID- 8275924
TI  - Induction of immature thymocyte proliferation after castration of normal male
      mice.
AB  - The physiological basis and immunological significance of thymic enlargement in
      castrate male animals is not known. We used normal male C57 Bl/6 mice to examine
      the contribution of in situ thymocyte proliferation to castration-induced
      enlargement of the thymus. Animals castrated at 8-10 weeks of age were compared
      to normal intact males. Thymocytes were examined 4-120 days after castration
      using flow cytometry to determine DNA content and thus the number of cells in
      active phases of the cell cycle. These properties were examined in unseparated
      thymocytes and in phenotypic subpopulations defined by expression of CD3, CD4,
      and CD8. For thymocytes obtained from intact control glands, a mean of 11.0 +/-
      1.0% were in active phases of the cell cycle. The percentage of cycling
      thymocytes was increased to a mean of 22.5 +/- 1.9% in the week after castration
      (P < 0.001). This change occurred in the absence of significant thymic
      enlargement. At 8-10 days after castration, thymic weight increased abruptly to a
      new steady state which was double that of intact controls (78.0 +/- 4.1 vs. 39.1
      +/- 2.6 mg; P < 0.001). In these enlarged glands, only 9.9 +/- 0.8% of cells were
      cycling, which was not significantly different than controls (P > 0.3).
      Proliferating cells identified in fixed thymus tissue sections after in vivo
      administration of bromodeoxyuridine were located in the subcapsular cortex and
      medulla. Analyses of thymocyte subpopulations indicated that most cycling cells
      had immature phenotypes (CD4+CD8+, CD4-CD8+, and CD3lo or CD3-). Castrate glands
      studied in the steady state period 8-120 days after surgery contained
      significantly fewer CD3+ cells than intact controls (P < or = 0.045). The
      findings suggest an intrathymic role for androgens in affecting generation of the
      mature T cell repertoire.

PMID- 8275925
TI  - Prolactin-releasing activity of neurohypophysial hormones: structure-function
      relationship.
AB  - Oxytocin (OT) and arginine vasopressin (AVP) have been reported to release PRL
      both in vivo and in vitro. The objectives of this study were 1) to compare the
      potencies of the PRL-releasing activities of OT and TRH using cultured anterior
      pituitary (AP) cells, and 2) to assess the PRL-releasing activity of naturally
      occurring neurohypophysial hormones and selected analogs. AP cells were incubated
      with peptides for 15 min, and medium PRL concentrations were determined by enzyme
      linked immunosorbent assay. OT at 25, 100, and 400 nM increased PRL release by
      110%, 175%, and 270%, respectively; higher concentrations (1600 and 6400 nM) did
      not cause a further increase in PRL release. TRH was 5-10 times more potent than
      OT on a molar basis. GH3 cells, a somatommamotroph tumor cell line, did not
      respond to OT and related compounds, but showed a similar responsiveness to TRH
      as AP cells. Twelve neurohypophysial peptides and selected analogs were incubated
      with AP cells, and their relative PRL-releasing activities were compared. OT and
      arginine vasotocin (AVT) showed the highest PRL-releasing activity. T4-G7
      oxytocin, mesotocin, isotocin, lysine vasotocin, and AVP showed a moderate PRL
      releasing activity, whereas, lysine vasopressin, desmopressin, tocinoic acid,
      pressinoic acid, and oxytocin free acid showed very low or no PRL-releasing
      activity. Coincubation of OT, AVT, or AVP with a specific OT receptor antagonist
      abolished their PRL-releasing activity. We conclude that 1) OT and related
      peptides are capable of stimulating PRL release in vitro, but their potencies are
      significantly lower than that of TRH; 2) unlike primary AP cells, GH3 cells are
      unresponsive to OT and related peptides; 3) AVT and AVP probably stimulate PRL
      release by acting via an OT receptor; and 4) the amino acid residues in positions
      3 and 8 in the peptide chain and an amidated C-terminus are critical for the PRL
      releasing activity of the neurohypophysial peptides.

PMID- 8275926
TI  - Activin modulates the intracellular signaling system activated by gonadotropin
      releasing hormone: dual effect on calcium messenger system and protein kinase-C
      pathway.
AB  - This study was performed to assess the effects of activin on intracellular
      mechanisms involved in GnRH action. When rat pituitary cell cultures were
      pretreated with activin-A (5-80 ng/ml) for 3 days, subsequent FSH and LH release
      (percentage of total cellular FSH and LH released during 4 h) in response to GnRH
      (10(-10)-10(-6) M) was not significantly different from that in cells pretreated
      with medium alone. In contrast, activin pretreatment increased the potency of
      both A23187 (Ca2+ ionophore) and phorbol 12-myristate 13-acetate [a protein
      kinase-C (PKC) activator] as secretagogues for FSH and LH release. FSH or LH
      release in response to another Ca(2+)-mobilizing secretagogue, maitotoxin (an
      activator of the GnRH receptor-associated Ca2+ channel), was not increased by
      activin. Although PKC is capable of influencing the actions of Ca2+, which is
      believed to be the second messenger for GnRH action, neither GnRH- nor maitotoxin
      stimulated gonadotropin release was increased by activin even when the influence
      of activin on PKC was eliminated by the addition of a PKC inhibitor
      (staurosporine; 100 nM) during the final 30 min of the 3-day pretreatment period.
      These results indicate that although activin does not influence GnRH action with
      regard to gonadotropin release, it increases the sensitivity of the system
      regulating gonadotropin release to increases in cytosolic Ca2+ concentrations and
      PKC activation. Furthermore, activin appears to exhibit an inhibitory effect(s)
      at some point(s) in GnRH action in a PKC-independent manner, which could be
      responsible for opposing the increased sensitivity of the gonadotrope to Ca2+.
      The differential effects of activin on gonadotropin release in response to Ca(2+)
      mobilizing secretagogues (ionophore and maitotoxin) raise the possibility that
      the activity of the GnRH receptor-associated Ca2+ channel may be suppressed by
      activin.

PMID- 8275927
TI  - Activation of the Ca2+ message system by parathyroid hormone is dependent on the
      cell cycle.
AB  - To verify whether the heterogeneous intracellular calcium ([Ca2+]i) responses to
      PTH observed in the UMR 106-01 osteogenic sarcoma cells are secondary to cell
      cycle asynchrony or to genotypic differences within the population, we
      synchronized cell monolayers at the G1/S boundary using a sequential thymidine
      aphidicolin block. Video image analysis of fura-2-loaded cells revealed that PTH
      (10(-7) M) induced transient increases of [Ca2+]i preferentially in cells in S
      phase (82% response frequency, n = 63; 286 +/- 33% of baseline, n = 29), whereas
      cells in G1 phase responded poorly to PTH (10% response frequency, n = 51; 140 +/
      8% of baseline, n = 5). In contrast, cell exposure to 2% fetal calf serum was
      followed by [Ca2+]i transients in 83% (n = 42) of cells in G1 phase, but in only
      25% (n = 63) of cells in S phase, with similar response amplitude. Hormonal
      responsiveness was heterogeneous in small clones obtained from single UMR 106-01
      cells, with response frequency similar to that observed in nonsynchronized
      cultures. Pretreatment with either La3+, nifedipine, or pertussis toxin reduced
      both frequency and amplitude of PTH response in S phase to levels close to G1
      phase, whereas there was no significant difference in inositol trisphosphate
      generated by PTH stimulation in either phase. Therefore, the heterogeneous
      [Ca2+]i responses of UMR 106-01 cells to hormonal stimulation is dependent on the
      phase of the cell cycle, rather than on genotypic heterogeneity. The switch from
      the G1 to the S phase mode of response is driven by active coupling between the
      PTH receptor and a Ca2+ channel through a pertussis toxin-sensitive G protein.

PMID- 8275928
TI  - An oxytocin receptor antagonist infused into the supraoptic nucleus attenuates
      intranuclear and peripheral release of oxytocin during suckling in conscious
      rats.
AB  - We tested the hypothesis that oxytocin (OXT) released within the supraoptic
      nucleus (SON) during suckling in lactating rats facilitates its own intranuclear
      release and thereby stimulates its secretion into blood during the milk ejection
      reflex. In the first study, to examine the positive feedback action of OXT
      released within the SON, microdialysates of the SON area were sampled before and
      during suckling. Either vehicle (1.0 microliter) or an OXT receptor antagonist
      (50 ng/microliters) was infused adjacent to the microdialysis probe into the SON
      area before suckling began. Compared to the corresponding presuckling values
      (100%), the OXT content in microdialysates sampled during the suckling period
      increased after vehicle treatment (to 501 +/- 174%; P < 0.01), whereas infusion
      of the OXT antagonist significantly (P < 0.05) attenuated the rise in the release
      of OXT during suckling (130 +/- 22.0%). In the second study, the influence of
      intranuclear OXT on release of OXT into the blood during suckling was examined.
      Compared to those in rats infused with vehicle into both SON before suckling
      started (100%), injection of the OXT antagonist decreased the concentration of
      OXT in plasma (to 32.1 +/- 5.50%; P < 0.05) and the milk transfer to the pups
      during the suckling period (to 30.2 +/- 13.3%; P < 0.01). Although the
      neuroendocrine response to suckling was attenuated in rats receiving the OXT
      antagonist, maternal behavior, assessed as the time at which six to eight pups
      began suckling and the time from the onset until the occurrence of the third milk
      ejection reflex, was unaffected. These findings provide evidence for a receptor
      mediated positive feedback action of OXT on its own release within the SON during
      suckling. The amplification of intranuclear release of OXT is needed for the
      release of appropriate amounts of OXT into the bloodstream to stimulate milk
      transfer to the suckling pups.

PMID- 8275929
TI  - Corticosterone in vivo increases pituitary follicle-stimulating hormone (FSH)
      beta messenger ribonucleic acid content and serum FSH bioactivity selectively in
      female rats.
AB  - Experimental objectives were to determine: 1) if the native glucocorticoid,
      corticosterone (B), can selectively increase pituitary FSH and FSH beta messenger
      RNA (mRNA) in the presence or absence of a GnRH signal; and 2) if B affects the
      biological activity of the gonadotropins. Metestrous female rats were implanted
      with cholesterol or B. Each implant group received 100 micrograms GnRH antagonist
      or control injections every 48 h beginning at the time of implantation, and were
      killed 5 days later. B significantly increased bioactive serum FSH, with or
      without GnRH antagonist. GnRH antagonist decreased bioactive serum FSH.
      Immunoreactive serum FSH was not affected by any treatment. B did not affect
      bioactive serum LH, but GnRH antagonist significantly suppressed bioactive serum
      LH. Immunoreactive serum LH was significantly lowered by either B or GnRH
      antagonist. Neither bioactive nor immunoreactive pituitary FSH or LH content were
      affected by B, GnRH antagonist, or combined treatments, and no treatment affected
      alpha or LH beta mRNA. B significantly increased FSH beta mRNA specifically, in
      the presence or absence of GnRH antagonist. These results demonstrate that
      corticosterone can increase biological activity of secreted FSH and increase FSH
      beta mRNA in the absence of a GnRH signal, suggesting a direct effect on the
      anterior pituitary gland.

PMID- 8275930
TI  - Osteoblasts mediate thyroid hormone stimulation of osteoclastic bone resorption.
AB  - Thyroid hormones increase bone turnover in vivo and stimulate bone resorption in
      vitro. Clinical states associated with excess circulating thyroid hormone levels
      are known to produce osteoporosis. To determine the effect of T3 on bone
      resorption, we used an isolated rat osteoclast bone resorption assay in the
      absence or presence of added osteoblasts. This makes it possible to distinguish
      between direct and indirect effects of thyroid hormones on osteoclasts. In short
      settlement osteoclast cultures, which contain relatively few osteoblasts, 24-h
      treatment with T3 (10(-10)-10(-8) M) produced no stimulation of bone resorption.
      However, after 48-h incubation in the presence of T3, an increase in resorption
      was observed (2.3-fold at 10(-9) M). In cocultures of osteoclasts and osteoblasts
      (UMR 106-01 osteoblast-like cells or long settlement cultures), T3 stimulated
      resorption at 24 h. Furthermore, stimulation of resorption occurred when
      osteoblasts (UMR 106-01 or rat calvarial cells) were pretreated with T3 and the
      subsequent osteoblast-osteoclast cocultures conducted for 24 h in the absence of
      T3. Thus, direct exposure of osteoclasts to T3 was not required for the
      stimulatory effect. Treatment for 48 h with T3 (10(-9) M) or PTH (10(-8) M) had
      no effect on bone resorption in osteoblast-free cultures derived from human
      osteoclastoma tumours. T4 was 100-fold less potent than T3 as a stimulator of
      osteoclast activity, and rT3 had no effect. T3-induced stimulation was inhibited
      by salmon calcitonin (10(-10) M). These findings indicate that thyroid hormone
      can act on osteoblasts to indirectly stimulate osteoclastic bone resorption.

PMID- 8275931
TI  - Calmodulin-binding peptides interfere with melanocyte-stimulating hormone
      receptor activity and stimulate adenosine 3',5'-monophosphate production in M2R
      mouse melanoma cells.
AB  - The MSH receptor belongs to a unique class of G-protein-coupled receptors, in
      which calcium ions control the binding affinity of MSH by a yet unknown
      mechanism. Possible involvement of a calcium-binding protein [e.g. calmodulin
      (CaM)] in the regulation of MSH receptor activity has been studied in the M2R
      mouse melanoma cell line. In this study, we tested the inhibitory effects of a
      group of calmodulin-binding peptides (CBPs) on MSH receptor activities in intact
      M2R cells and membrane preparations derived from them. We also report here on
      stimulatory effects of CBPs on cAMP production in M2R cells that could not be
      produced in other cell lines lacking MSH receptors. This group of CBPs includes
      synthetic peptides comprising the CaM-binding domains of Ca2+/CaM-dependent
      enzymes, cytotoxic venom peptides, and peptide hormones that have been reported
      to directly interact with CaM. The results show that CBPs, at micromolar
      concentrations, inhibit MSH binding and consequent adenylate cyclase stimulation
      in a specific and concentration-dependent manner, but have no effect on adenylate
      cyclase stimulation by prostaglandin E1. On the other hand, when MSH was omitted
      and forskolin (0.5-1 microM) was added instead, CBPs had the opposite effect on
      cAMP production, stimulating it in M2R cells, but not in other cell types tested.
      Thus, these peptides can be considered as antagonists of MSH receptor and partial
      agonists of M2R adenylate cyclase. In contrast to MSH, the stimulatory effects of
      CBPs were unaffected by EGTA, suggesting a Ca(2+)-independent action of these
      peptides. Using phospholipid vesicles and M2R cells, we recently showed that CBP
      activity in M2R cells may include direct partition into the lipid bilayer of the
      cell membrane, permitting interaction with hydrophobic lipid-inserted domains of
      components of the signal transducing machinery. Based on these findings, we
      suggest that the mechanism of action of CBPs in the M2R cells includes two major
      components: 1) interaction with the cell surface membrane and penetration into
      the lipid milieu, and 2) interaction with exposed or lipid-embedded protein
      epitopes intrinsically associated with the MSH-receptor system, thereby affecting
      the MSH receptor cascade.

PMID- 8275932
TI  - Pituitary adenylate cyclase-activating polypeptide regulation of AtT-20/D16v
      corticotrope cell proopiomelanocortin expression and secretion.
AB  - The hypothalamic peptides pituitary adenylate cyclase-activating polypeptides
      (PACAPs) may play central roles in the regulation of anterior pituitary gland
      function. The two pro-PACAP-derived peptides, PACAP38 and PACAP27, are
      posttranslationally processed from a common precursor molecule and share amino
      acid sequence homology with vasoactive intestinal peptide (VIP). To further
      evaluate and compare the physiological roles of these peptides, we have examined
      the short and long term effects of PACAP38, PACAP27, and VIP on POMC-related
      peptide production in the mouse AtT-20/D16v corticotrope cell line. Short term
      (0.5- to 5-h) treatment of AtT-20/D16v cells with PACAP38, PACAP27, or VIP
      elicited similar concentration-dependent and biphasic stimulation of ACTH
      release. Half-maximal stimulation of the higher potency phase was attained with 1
      2 nM peptide; maximal secretion was observed at peptide concentrations greater
      than 100 nM. Similar 2- to 3-fold maximal stimulation of ACTH secretion was
      elicited by all three bioactive peptides; linear sustained ACTH secretion was
      observed. Long term (12- to 72-h) treatment of AtT-20/D16v cultures with these
      peptides resulted in substantially decreased rates of cellular division, with a
      concomitant increase in cell size and formation of cell processes characteristic
      of cellular differentiation. These morphological changes coincided with a
      sustained 2-fold increase in AtT-20 corticotrope intracellular hormone content
      and secretion. Northern blot analysis demonstrated a parallel induction of POMC
      mRNA expression by the PACAP38, PACAP27, and VIP peptides. These results suggest
      that AtT-20/D16v cells possess primarily the type II PACAP receptor subtype,
      which binds PACAP38, PACAP27, and VIP with apparent equal affinity. Furthermore,
      the long term effects of these peptides implicate a potentially significant role
      for PACAP and VIP peptides in the mediation of altered pituitary gland functions.
      In this vein, the PACAPs may prove to be unique regulators of neuroendocrine
      function and development.

PMID- 8275933
TI  - Characterization of different sizes of rat luteinizing hormone/chorionic
      gonadotropin receptor messenger ribonucleic acids.
AB  - The LH/CG receptor is uniquely expressed in the gonads of both sexes at specific
      stages of development. In ovaries, its expression marks particular steps of the
      ovulation cycle. An enigmatic aspect of expression of the LH/CG receptor is the
      dramatically diverse transcript sizes [from 7 to < 1 kilobase (kb)] and
      development-dependent expression of different sizes of mRNAs. It has been thought
      that mRNAs larger than 2.1 kb encode full-length receptors, whereas those smaller
      than 2.1 kb encode truncated receptor, because the full-length coding sequence is
      2.1 kb. As a first step in elucidation of these diverse mRNAs and corresponding
      proteins, we have produced a series of cDNA clones and determined their DNA
      sequences and deduced the amino acid sequences of the resulting proteins. Our
      data demonstrate that variant mRNAs are produced by alternate splicing and
      polyadenylation, and they encode significantly shorter truncated receptor
      peptides. Surprisingly, many of these variant mRNAs are larger than 2.1 kb, and
      some are 4.2 kb. Some of them are polyadenylated in introns 3, 4, and 10. These
      alternate mRNAs were successfully expressed in 293 cells to produce receptor
      peptides 81, 116, and 294 amino acids in length compared to the wild-type
      receptor, which consists of 674 amino acids. Although these receptor peptides are
      not secreted, they are capable of binding the hormone, indicating the presence of
      a hormone contact site(s) in the short peptide fragments, particularly the N
      terminal 81-amino acid segment. The data presented here will be helpful for
      understanding the functions of different sizes of mRNAs and also be valuable in
      studies designed to investigate whether individual cells express a specific
      message or multiple messages and how different classes of LH/CG receptor mRNAs
      are selectively expressed dependent on differentiation and development of the
      gonads.

PMID- 8275934
TI  - Anterior pituitary proopiomelanocortin expression is decreased in hypertensive
      rat strains.
AB  - Studies comparing neuroendocrine differences between the spontaneously
      hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY) strains have
      suggested altered anterior pituitary corticotrope expression of POMC associated
      with the development of hypertension in SHR animals. One major difficulty in
      comparing the SHR and WKY strains is that the two strains exhibit genetic
      differences unrelated to blood pressure status, because inbred in the SHR genome
      is a profile of behavioral characteristics different from those in the WKY,
      including hyperactivity in a novel environment and hyperreactivity in responding
      to stress. The present studies examine two new inbred rat strains, the WKHT and
      WKHA, which independently express the hypertension and behavioral traits,
      respectively. Together with the SHR and WKY, these genetically related,
      homozygous strains permit a more definitive means of examining the neuroendocrine
      correlates of either hypertension or behavior. The adult (5-month-old) male
      anterior pituitary gland content of the POMC peptides beta-endorphin and ACTH was
      decreased approximately 50% in the SHR and WKHT strains compared to that in the
      WKY strain, whereas hormone levels in the WKHA strain were not significantly
      different from those in the WKY strain. Reduced POMC peptide levels were,
      therefore, specifically associated with the hypertensive trait. Hormone content
      in prehypertensive weanling (5- to 7-week-old) SHR and WKHT animals was also
      reduced approximately 35% compared to that in WKY animals. Northern blot analysis
      identified a 45% decrease in POMC mRNA expression in the hypertensive SHR and
      WKHT strains, which paralleled the changes in tissue hormone content. Using both
      immunocytochemistry and in situ hybridization histochemistry, the number of
      labeled cells per unit area of tissues section was reduced approximately 45% in
      anterior pituitary tissues from SHR and WKHT rats compared to that in WKY
      tissues. The levels of POMC mRNA per cell, determined by quantitative
      densitometry, were not statistically different in the anterior pituitaries of
      WKHT, SHR, and WKY rats. The decrease in hormone content and POMC mRNA levels
      may, thus, reflect decreased anterior pituitary gland corticotrope populations.
      Although POMC peptide levels in the anterior pituitaries of adult WKHA animals
      were not significantly different from those in WKY animals, the morphological
      studies demonstrated a 30% increase in the corticotrope population in the WKHA
      strain. In contrast, POMC mRNA levels in WKHA animals were decreased 30%, and the
      amount of POMC mRNA per corticotrope was decreased approximately 35% compared to
      that in WKY, SHR, and WKHT tissues.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8275935
TI  - Expression of tumor necrosis factor-alpha (TNF alpha) receptors and selective
      effect of TNF alpha on the inner cell mass in mouse blastocysts.
AB  - The presence of tumor necrosis factor-alpha (TNF alpha) receptors was
      demonstrated at the cell surface of mouse blastocysts by indirect
      immunofluorescence. Amplification of total cDNA from these embryos indicated that
      only the p60 form of the TNF alpha receptor was expressed. Amplification of the
      p80 form remained negative. Blastocysts were cultured with 0.5, 5.0, or 50 ng/ml
      TNF alpha and examined for their morphology and cell proliferation rate. Doses of
      5.0 and 50 ng/ml delayed the morphological development after 24 h, but this
      effect was no longer detected after 48 h. Overall cell proliferation was
      decreased by 15% with 50 ng/ml TNF alpha after 24 h and with all three
      concentrations after 48 h. Differential staining of the two embryonic cell
      lineages revealed that the reduction in cell number was at the expense of the
      inner cell mass, the cell group responsible for forming the fetal layers after
      implantation. This inhibition was not mediated by cytotoxicity, as the proportion
      of dead ICM cells remained low in the presence of TNF alpha. Our data indicate
      that the expression of TNF alpha receptors is developmentally regulated before
      implantation, and that preimplantation embryos are responsive to TNF alpha.

PMID- 8275937
TI  - Phenotypic change of endothelin receptor subtype in cultured rat vascular smooth
      muscle cells.
AB  - An endothelium-derived vasoactive peptide, endothelin (ET)-1, is a potent
      constrictor and mitogen for vascular smooth muscle cells (VSMC). To determine
      whether vascular ET receptor subtypes phenotypically change during in vitro
      culture conditions, we studied the expression of ET receptor subtypes, ET-induced
      phosphoinositide breakdown, and DNA synthesis in cultured rat VSMCs during serial
      passages. Binding studies using [125I]ET-1 as a radioligand revealed that the
      early passage (10th-15th) VSMCs possess predominantly ETA receptors, whereas the
      late passage (30th-35th) VSMCs possess predominantly ETB receptors in addition to
      ETA receptors. Northern blot analysis using cDNAs for rat ETA and ETB receptors
      as probes also demonstrated the predominant expression of ETA receptor mRNA in
      the early passage and ETB receptor mRNA in the late passage, whereas only ETA
      receptor mRNA was expressed in intact medium of rat aorta. ET-1 had a greater
      effect than ET-3 in stimulating inositol 1,4,5-trisphosphate formation, whereas
      ET-1 and ET-3 almost equipotently stimulated insitol 1,4,5-trisphosphate
      formation in the late passage VSMC even in the presence of an ETA receptor
      antagonist. ET-1-induced DNA synthesis was almost completely inhibited by an ETA
      receptor antagonist in the early passage VSMC. In contrast, ET-1, ET-3, and an
      ETB receptor agonist remarkably stimulated DNA synthesis in the late passage
      VSMC, which was completely inhibited by a nonselective ET receptor antagonist,
      but not by an ETA receptor antagonist. Our data provide the first evidence that a
      phenotypic change in VSMC in culture is concomitantly associated with a change in
      the ET receptor subtype that potentiates mitogenic activity and suggest that
      switching the ET receptor subtype from ETA to ETB during phenotypic change may in
      part contribute to the development of vascular lesions, such as in
      atherosclerosis.

PMID- 8275936
TI  - Expression of metalloproteinases and tissue inhibitors of metalloproteinases in
      human osteoblast-like cells: differentiation is associated with repression of
      metalloproteinase biosynthesis.
AB  - To more clearly define the expression of metalloproteinases and tissue inhibitors
      of metalloproteinases (TIMPs) within the human osteoblast (hOB) lineage, normal
      hOB and human osteogenic sarcoma cells possessing various levels of alkaline
      phosphatase (a marker of commitment to the osteoblast lineage) were treated with
      bone-resorbing agents to determine their effect on the production of interstitial
      collagenase, stromelysin, 72-kilodalton (kDa) gelatinase, 92-kDa gelatinase, TIMP
      1, and TIMP-2. The results revealed that 1) normal hOB release copious amounts of
      72-kDa gelatinase, TIMP-1, and TIMP-2; 2) hOB production of 72-kDa gelatinase and
      TIMP-2 is not regulated by agents that promote bone resorption (e.g. phorbol-12
      myristate 13-acetate, recombinant human interleukin-1 beta, tumor necrosis factor
      alpha, PTH, and vitamin D3); 3) normal hOB fail to secrete collagenase,
      stromelysin, or 92-kDa gelatinase when cultured on plastic or a type I collagen
      substratum, even in response to bone-resorptive agents or mononuclear cell
      conditioned medium; 4) in contrast, certain of the osteogenic sarcoma cell
      populations produce collagenase, stromelysin, and 92-kDa gelatinase, especially
      when exposed to bone-resorbing stimuli; 5) in general, the capacity for
      metalloenzyme production by osteogenic sarcoma cell lines varies inversely with
      their alkaline phosphatase expression; and 6) the most committed (highest
      alkaline phosphatase) osteogenic sarcoma cell line, SAOS-2, precisely mimics the
      metalloproteinase profile of normal hOB. The results suggest that the expression
      of most metalloproteinases is under strict repression within the differentiated
      normal hOB, and cellular development is associated with diminished capacity to
      elaborate such enzymes.

PMID- 8275938
TI  - Effect of antiinsulin-like growth factor 1 on epidermal proliferation of human
      skin transplanted onto nude mice treated with growth hormone.
AB  - Recently it has been demonstrated that long-term administration of GH leads to
      increase of skin thickness. The aim of the present study was to determine whether
      this effect of GH is mediated by insulin growth factor 1 (IGF-1), which enhances
      epidermal proliferation. In order to address this question, human split-thickness
      grafts obtained from aged skin were grafted onto nude mice. One group of mice was
      treated systemically with GH, whereas a second group was treated with intradermal
      graft injections of anti-IGF-1 in addition to GH. A third group received
      distilled water and served as a control group. Histological and autoradiographic
      analyses were performed before and after engraftment. The GH-treated mice showed
      a significant increase in epidermal proliferation measured by epidermal thickness
      (analysis of variance with repeated measurements, P < 0.01) and labeled index
      (analysis of variance, P < 0.01) as compared to the control group. The
      intradermal injections of anti-IGF-1 reduced significantly the proliferative
      stimulatory effect of GH (P < 0.01). The present study emphasizes the role of IGF
      1 in the increased skin thickness observed after GH administration and provides a
      useful model for determining the effect of various compounds, including GH, on
      human skin.

PMID- 8275939
TI  - Cellular variations in heterotrimeric G protein localization and expression in
      rat pituitary.
AB  - The secretory cells of the anterior pituitary are regulated by hypothalamic and
      target endocrine hormones. In many cases, intracellular signaling after ligand
      binding to cell surface receptors is mediated by heterotrimeric G proteins. In
      this study, cells from the rat pituitary and two pituitary cell lines (GH3 and
      AtT-20 cells) were doubly labeled by immunofluorescence with specific rabbit
      antibodies to the alpha-subunits of G proteins (Gs, Gi1-3, or Gq) and monoclonal
      antibodies against pituitary hormones (GH, PRL, beta LH, beta TSH, or beta FSH)
      to identify specific cell types. Gs, Gi, and Gq were detected in all secretory
      types, but differences were found in their levels of expression and cellular
      distribution. The cell periphery was the predominant site of localization of all
      these G proteins. In addition, both Gi3 and at least one member of the Gq family
      were seen by immunofluorescence on intracellular sites typical of the Golgi
      region. By immunogold labeling, alpha i3 was localized to membranes of Golgi
      cisternae in sections of rat pituitary and GH3 cells, where it was concentrated
      on the cis-side of the Golgi stack. These findings demonstrate that G proteins
      are widely expressed in anterior pituitary cells and further support a role for
      Gi alpha 3, and possibly Gs, in intracellular membrane trafficking.

PMID- 8275940
TI  - Gonadotropin-releasing hormone directly induces apoptotic cell death in the rat
      ovary: biochemical and in situ detection of deoxyribonucleic acid fragmentation
      in granulosa cells.
AB  - The majority of ovarian follicles undergo atresia through a mechanism involving
      apoptotic cell death. Although GnRH and its agonists have been shown to suppress
      ovarian growth and differentiation in hypophysectomized rats, studies on the
      induction of follicle atresia by GnRH are contradictory. In the present study,
      the direct effect of GnRH on the occurrence of apoptosis in the ovary was
      investigated in hypophysectomized estrogen-treated immature rats. Starting 2 days
      after operation and estrogen capsule implantation, rats were treated with a GnRH
      agonist (GnRHa; [desGly10,D-Phe6,Pro9-N-ethylamide] GnRH; 50
      micrograms/injection, twice daily). Total ovarian DNA was isolated 48 h later,
      labeled at the 3'ends with [32P]dideoxy ATP, and size-fractionated. Compared to
      that in control animals, treatment with GnRHa increased DNA fragmentation in
      multiples of 180 basepairs, a hallmark of apoptosis, demonstrating that GnRH
      directly increases ovarian apoptotic cell demise. In contrast, FSH treatment (10
      micrograms/injection, twice daily) decreased apoptotic DNA fragmentation, and the
      antiapoptotic effect of FSH was partially blocked by concomitant treatment with
      GnRHa. The apoptosis-inducing effect of GnRHa was time and dose dependent, with a
      significant increase seen after 24 h of treatment and a maximal 5.5-fold increase
      with 10 micrograms GnRHa/injection. Similar to studies using DNA isolated from
      whole ovaries, DNA obtained from isolated granulosa cells also showed a time- and
      dose-dependent increase in DNA fragmentation after GnRHa treatment. The effect on
      DNA fragmentation by GnRHa was mediated by ovarian GnRH receptors, because a
      potent GnRH receptor blocker, Azaline B, prevented GnRHa action. In addition, in
      situ end labeling of DNA using digoxigenin-dideoxy-UTP showed that DNA
      fragmentation was confined to the granulosa cells of preantral and antral
      follicles. No GnRHa-induced apoptosis was detected in granulosa cells of primary
      follicles or in thecal and interstitial cells. These data suggest that GnRH
      directly increases apoptotic cell death in the ovary, and the GnRH action is
      confined to the granulosa cells. These data provide a basis for future studies on
      the mechanism of follicular atresia and the regulation of ovarian endonuclease by
      GnRH.

PMID- 8275941
TI  - Effects of nephrectomy and adrenalectomy on the renin-angiotensin system of
      transgenic rats TGR(mRen2)27.
AB  - The transgenic rat TGR(mRen2) develops severe hypertension with high renin
      activity in the adrenal and low renin activity in the kidney. To clarify the role
      of the adrenal gland as a source of circulating renin in TGR rats, we
      investigated the effects of nephrectomy (NEPEX) and adrenalectomy (ADX) on the
      adrenal and plasma renin-angiotensin system. TGR rats had a high basal plasma
      renin concentration (PRC; 18.2 +/- 1.0 ng angiotensin-I (AngI)/ml.h) compared
      with Harlan Sprague-Dawley (SD) rats (7.4 +/- 0.5 ng AngI/ml.h; P < 0.01) and SD
      rats of the Hannover strain from which the TGR rat was derived (5.3 +/- 0.6 ng
      AngI/ml.h, P < 0.01); TGR rats also had high adrenal renin (83.3 +/- 8.9)
      compared with Harlan SD rats (5.5 +/- 0.7; P < 0.01) and Hanover SD rats (6.1 +/-
      0.6 ng AngI/ml.h). NEPEX markedly increased PRC (82.4 +/- 18.8 ng AngI/ml.h, P <
      0.01) and adrenal renin levels (386.3 +/- 43.9 ng AngI/adrenal.h; P < 0.01) in
      TGR rats. ADX significantly lowered control levels of PRC and plasma AngII in the
      TGR rats (19.0 +/- 1.2 to 7.7 +/- 1.2 ng AngI/ml.h and 33.5 +/- 5.6 to 12.8 +/-
      2.1 pg/ml, respectively) and suppressed the increases in PRC (119.4 +/- 20.2 to
      61.8 +/- 4.0 ng AngI/ml.h) and plasma AngII (95.8 +/- 9.8 to 55.1 +/- 4.3 pg/ml;
      P < 0.01) caused by NEPEX in TGR rats. However, the levels of PRC and plasma
      AngII remained high after NEPEX/ADX in TGR rats. Our results suggest that the
      adrenal gland is one of the main sources of circulating renin in the TGR rat, but
      other extrarenal sources of plasma renin also exist in these animals.

PMID- 8275942
TI  - Altered gene expression for tumor necrosis factor-alpha and its receptors during
      drug and dietary modulation of insulin resistance.
AB  - As obesity is a major risk factor for noninsulin-dependent diabetes mellitus,
      adipose tissue may generate a mediator that influences the activity of insulin on
      various target tissues. Recent evidence suggests that a cytokine, tumor necrosis
      factor-alpha (TNF alpha), may serve this role. This study investigates whether
      the expression of TNF alpha and its receptors is modulated during drug treatment
      to reduce insulin resistance. The effects of moderate weight loss by dietary
      restriction were also examined. We show here that a marked induction of TNF alpha
      mRNA occurs in adipose tissues from a mouse model of obesity-linked diabetes
      (KKAy) compared to that in nondiabetic mice (C57). Likewise, RNA transcripts
      encoding TNF R2 receptors (p75) were significantly increased in fat tissues of
      the obese diabetic animals. In muscle from these diabetic animals, RNA
      transcripts encoding both TNF R1 (p55) and R2 were significantly elevated,
      although R2 transcript abundance was less elevated than in fat. We also observed
      that the overexpression of mRNA for TNF alpha and both of its receptors could be
      at least partly normalized by treatment of the diabetic animals with the insulin
      sensitizing agent pioglitazone. Treating of the obese diabetic animals by food
      restriction reduced the expression of mRNA for TNF R2 in muscle, but not fat.
      These results clearly indicate that gene expression for the TNF systems can be
      regulated by an insulin-sensitizing drug and reduction of body weight. Such
      findings support a role for this cytokine in the insulin-resistant diabetic state
      and show its modulation by therapies that reverse the disorder.

PMID- 8275943
TI  - Threonine for alanine substitution at position 109 of transthyretin
      differentially alters human transthyretin's affinity for iodothyronines.
AB  - The heterozygous substitution of threonine for alanine at amino acid 109 of human
      transthyretin (TTR) increases its affinity for T4. We compared the affinity of
      recombinant wild-type (WT) and Thr109-TTRs for various iodothyronines in an
      attempt to elucidate how this mutation alters the T4-binding site. Homozygous WT
      and Thr109-TTRs were expressed recombinantly in Escherichia coli, and
      heterozygous Thr109-TTR was purified from plasma. The affinities of the
      iodothyronines for TTR were determined by measuring [125I]T4 bound by TTR in the
      presence of increasing concentrations of unlabeled iodothyronines. Homozygous
      Thr109-TTR bound T4 with an affinity slightly, but not significantly, greater
      than that of heterozygous Thr109-TTR. The affinity of Thr109-TTR for all
      iodothyronines was higher than that of WT TTR. However, the Thr109 mutation
      increased TTR's affinity for T4, Triac (triiodothyroacetic acid), and T3 to a
      greater extent than it did for Tetrac (tetraiodothyroacetic acid), EMD21388
      (3',5'-dibromo-4',6'-dihydroxy-3-methylflavone), and dextro-T4. These data
      demonstrate that a subtle change in the structure of the T4-binding channel in
      TTR differentially alters the affinity of binding of various iodothyronines and
      suggests that site-directed mutagenesis of residues within the binding channel
      might clarify the relative importance of specific domains of this binding
      channel.

PMID- 8275944
TI  - Regulation of c-fos expression in adipose and muscle tissue of diabetic rats.
AB  - Insulin treatment of control rats demonstrated a marked 8-fold transient increase
      (15 min) in c-fos mRNA in white adipose tissue, which returns to basal levels by
      5 h. Similarly, insulin treatment resulted in a rapid 9-fold increase in cardiac
      muscle c-fos mRNA, which also returned to control values by 1 h. By contrast,
      insulin treatment resulted in only a small increase in c-jun mRNA levels in both
      adipose tissue and cardiac muscle. Similarly, the expression of c-jun mRNA was
      only slightly responsive to insulin in these tissues from streptozocin-induced
      insulin-deficient diabetic rats. However, insulin treatment of insulin-deficient
      diabetic rats resulted in a prolonged increase in c-fos message levels in adipose
      tissue without any significant change in the time course of c-fos mRNA
      induction/repression in cardiac muscle. These data demonstrate that in contrast
      to c-jun, c-fos is transiently increased in both cardiac muscle and adipose
      tissue by insulin treatment. Furthermore, transrepression of the c-fos gene is
      specifically attenuated in adipose tissue of insulin-deficient diabetic rats, but
      not in cardiac muscle.

PMID- 8275945
TI  - Differentiation of human bone marrow osteogenic stromal cells in vitro: induction
      of the osteoblast phenotype by dexamethasone.
AB  - Human bone marrow stromal cells were examined for their osteogenic potential in
      an in vitro cell culture system. Dexamethasone (Dex) treatment induced
      morphological transformation of these cells from an elongated to a more cuboidal
      shape, increased their alkaline phosphatase activity and cAMP responses to PTH
      and prostaglandin E2, and was essential for mineralization of the extracellular
      matrix. Dex-induced differentiation of human bone marrow stromal cells was
      apparent after 2-3 days of treatment and reached a maximum at 7-14 days, as
      judged by alkaline phosphatase activity, although induction of osteocalcin by
      1,25-dihydroxyvitamin D3 was attenuated by Dex. Withdrawal of Dex resulted in an
      enhancement of the 1,25-dihydroxyvitamin D3-induced secretion of osteocalcin,
      whereas alkaline phosphatase activity and the cAMP response to PTH remained at
      prewithdrawal levels. The steady state mRNA level of osteonectin was not affected
      by Dex. Our results, which demonstrate that Dex conditions the differentiation of
      human bone marrow osteogenic stromal cells into osteoblast-like cells, support
      the hypothesis of a permissive effect of glucocorticoids in ensuring an adequate
      supply of mature osteoblast populations. Furthermore, the established human bone
      marrow stromal cell culture provides a good model of an in vitro system to study
      the regulation of differentiation of human bone osteoprogenitor cells.

PMID- 8275946
TI  - The relationship between 3',5'-cyclic adenosine monophosphate and calcium in
      mediating follicle-stimulating hormone signal transduction in Sertoli cells.
AB  - FSH signal transduction in Sertoli cells involves the generation of cAMP and
      calcium as second messengers; however, the relationship between these two signals
      is not clear. In order to determine whether these were serial or parallel
      signals, we studied cytosolic calcium levels in freshly isolated rat Sertoli
      cells using maneuvers to dissociate generation of endogenous cAMP from cytosolic
      calcium. Pretreatment with 1 mM MDL 12,330A, an adenylate cyclase inhibitor,
      reduced by greater than 90% increases in cytosolic calcium induced by FSH (97 +/-
      6 vs. 213 +/- 16 nM), whereas, despite adenylate cyclase blockade, 1 mM (Bu)2cAMP
      continued to elevate cytosolic calcium (from 87 +/- 6 to 182 +/- 23 nM),
      indicating the involvement of adenylate cyclase in the FSH-induced rise of
      cytosolic calcium. A cAMP antagonist, 1 mM Rp-cAMP, reduced by 75% the FSH
      induced rise of cytosolic calcium (115 +/- 14 vs. 213 +/- 16 nM), suggesting that
      endogenous cAMP levels generated by FSH are sufficient to activate the cytosolic
      calcium response to FSH. Pretreatment with pertussis toxin (1 mg/liter) to
      dissociate the FSH-receptor interaction from its G-protein-mediated linkage to
      adenylate cyclase also suppressed the FSH-induced rise in cytosolic calcium (97
      +/- 11 vs. 213 +/- 16 nM). Sertoli cells preincubated with 1 mM staurosporine, an
      inhibitor of protein kinases, exhibited a reduced calcium response to FSH (125 +/
      14 vs. 213 +/- 16 nM), suggesting that FSH-induced calcium flux might be
      mediated by protein kinase, presumably cAMP-dependent protein kinase A. The
      present findings therefore strengthen the premise that the cytosolic calcium
      response to FSH in Sertoli cells is predominantly attributable to serial
      signaling after the generation of endogenous cAMP.

PMID- 8275947
TI  - Implementing Ethical Guidelines for Publication of Research in Endocrine Society
      journals.

PMID- 8275948
TI  - Subcellular distribution of the long and short isoforms of the growth hormone
      (GH) receptor in rat adipocytes: both isoforms participate in specific binding of
      GH.
AB  - In rodents the GH receptor gene encodes long and short isoforms of the receptor
      that arise from alternate splicing of the mRNA transcript. To determine whether
      the long and short isoforms reside on the plasma membrane, we compared their
      sensitivity to mild digestion of adipocytes with trypsin. Immunofunctional assays
      were used to measure each isoform in adipocyte extracts. The GH-binding capacity
      of the short isoform in cell extracts was more than 5 times that of the long.
      Digestion of freshly isolated adipocytes with trypsin decreased the specific
      binding of [125I]human GH by 77%. The GH-binding capacities of the long and short
      isoforms in cell extracts were diminished by 68% and 18%, respectively. The
      relative insensitivity of the short isoform to digestion with trypsin suggests
      that much of it may be inaccessible to trypsin because it is located within the
      cell. When cells were allowed to recover for 2 h after digestion with trypsin, GH
      binding was restored. Analysis of cell extracts indicated net synthesis of the
      long isoform and further loss of the short. Adipocytes lost more than half of the
      short isoform during a 2-h incubation in vitro regardless of whether the cells
      were first digested with trypsin. Loss of the short isoform during this period
      appeared to be limited to the intracellular component, as the amount of the
      trypsin-sensitive component remained constant. The abundance of RNA transcripts
      that encode the long and short isoforms of the GH receptor remained unchanged
      when adipocytes were incubated in vitro for 3 h in the presence or absence of
      actinomycin-D. Therefore, the acute changes seen in these experiments do not
      reflect regulation of GH receptor gene transcription. Adipocytes appear to
      maintain a fixed ratio of the long and short isoforms of the GH receptor on their
      surface. Each isoform accounts for approximately half of the cell's GH-binding
      capacity.

PMID- 8275949
TI  - Molecular cloning of an ovine ovarian tissue inhibitor of metalloproteinases:
      ontogeny of messenger ribonucleic acid expression and in situ localization within
      preovulatory follicles and luteal tissue.
AB  - Secretion of a tissue inhibitor of metalloproteinases (TIMP-1) is initiated by
      ovine preovulatory follicles after the gonadotropin surge. In addition, TIMP-1 is
      a major secretory product of ovine corpora lutea. We have isolated an
      approximately full-length cDNA clone for TIMP-1 from an ovine luteal cDNA
      library. The 887-basepair cDNA obtained was 95%, 86%, and 77% identical to the
      reported nucleotide sequences of bovine, human, and mouse TIMP-1 cDNAs,
      respectively. Total cellular RNA was isolated from preovulatory follicles
      collected before (presurge; n = 5) or 12-14 h after (postsurge; n = 4) a LHRH
      induced gonadotropin surge (36 h after prostaglandin F2 alpha-induced
      luteolysis); from luteal tissue collected on days 3, 7, 10, 13, and 16 postestrus
      (n = 5, 5, 4, 5, and 5, respectively); and from purified populations of small (n
      = 4) and large (n = 3) luteal cells. Concentrations of TIMP-1 mRNA (picograms per
      micrograms tissue DNA) were increased in preovulatory follicles after exposure to
      a gonadotropin surge (P < or = 0.01). TIMP-1 mRNA was localized primarily to the
      granulosa layer of postsurge follicles by in situ hybridization. Concentrations
      of TIMP-1 mRNA in luteal tissue did not differ throughout the luteal phase (P =
      0.07). However, TIMP-1 mRNA was localized predominantly to specific cells located
      in the connective tissue surrounding and within day 3 corpora lutea. In situ
      hybridization of day 10 corpora lutea localized TIMP-1 mRNA predominantly to
      specific cells that were randomly dispersed throughout the luteal tissue. TIMP-1
      mRNA was expressed by purified populations of both small and large luteal cells
      collected from day 10 corpora lutea. Concentrations of TIMP-1 mRNA (picograms per
      micrograms DNA) were greater in the large luteal cell populations (P < or =
      0.0001). We conclude that 1) expression of TIMP-1 mRNA by the granulosa layer of
      ovine preovulatory follicles increased after the gonadotropin surge, whereas TIMP
      1 mRNA concentrations during the luteal phase remained constant; 2) during the
      luteal phase, TIMP-1 mRNA was localized to specific cells surrounding (day 3) or
      located within (day 10) the corpus luteum; and 3) expression of TIMP-1 mRNA was
      greatest in large luteal cells.

PMID- 8275950
TI  - Tumor necrosis factor-alpha inhibits the synthesis and release of human decidual
      prolactin.
AB  - Bone marrow-derived cells are major cellular components of human decidua, with
      macrophages comprising about 30% of the cells in term tissue. Because cytokines
      released by bone marrow-derived cells are known to affect hormone release in many
      tissues, we examined whether cytokines affect the release of PRL from human
      decidual cells. Exposure of primary decidual cell cultures from term pregnancies
      to tumor necrosis factor-alpha (TNF alpha), interleukin-1 alpha (IL-1 alpha), IL
      1 beta, transforming growth factor-beta (TGF beta), and IL-8 caused dose
      dependent inhibition of PRL release. Initial inhibition by each of the cytokines
      was noted after 24 h of exposure, and maximal inhibition of 33-60% occurred after
      3 or 4 days. The maximal inhibitions by TNF alpha, IL-1 alpha, IL-1 beta, TGF
      beta, and IL-8 were 60%, 55%, 46%, 36%, and 33%, respectively, and the half
      maximal effective doses of TNF alpha, IL-1 alpha, IL-1 beta, and TGF beta were
      70, 2.8, 0.6, and 40 pM, respectively. The cytokine-induced decrease in decidual
      PRL release was accompanied by a decrease in PRL synthesis. In contrast to the
      other cytokines, IL-6 had no effect on basal PRL release. TNF alpha, IL-1 alpha,
      IL-1 beta, and IL-8 also inhibited stimulation of the synthesis and release of
      PRL and PRL mRNA levels in response to insulin. The effect of the cytokines was
      not due to inhibition of cell proliferation, because the DNA content of the cells
      was not affected by cytokine treatment. These results strongly suggest that
      cytokines released by decidual macrophages and other bone marrow-derived cells
      may have a paracrine role in the regulation of decidual PRL expression.

PMID- 8275951
TI  - Influence of hypophysectomy on renal proteoglycans and their modulation by
      insulin-like growth factor-I and its receptor.
AB  - Hypophysectomy leads to growth retardation of the animals, which is believed to
      be related to the deficiency of certain growth factors influencing the metabolism
      and synthesis of glycoproteins. Conceivably, the extracellular matrix proteins
      (ECM) are also affected, in particular the sulfated proteoglycans (PGs). In this
      study, we investigated the status of the ECM proteins and sulfated PGs, and the
      expression and de novo synthesis of insulin-like growth factor-I (IGF-I) receptor
      (IGF-IR) in hypophysectomized (Hx) rats. The studies were extended to ascertain
      the effect of IGF-I on the de novo synthesis of glomerular ECM glycoproteins in
      Hx rats. An organ perfusion system was used in which isolated rat kidneys were
      radiolabeled with either [35S]sulfate or [35S]methionine, after which IGF-IR and
      ECM macromolecules were isolated and characterized by biochemical and tissue
      autoradiographic procedures. Hypophysectomy resulted in a fall in IGF-I levels in
      serum and isolated renal glomeruli. Reduced synthesis of ECM proteins, i.e. type
      IV collagen, laminin, and sulfated PGs, and reduced synthesis and mRNA expression
      of IGF-IR were observed in the glomeruli of the Hx rats. Tissue autoradiographic
      studies revealed a reduced grain density (concentration of radiation) over
      various cell types of the glomerulus. After inclusion of IGF-I in the perfusion
      medium not only was synthesis restored to normal in Hx rats, but it far exceeded
      the control basal values in the intact animals. Under the influence of IGF-I, the
      magnitude of increased synthesis of the ECM proteins, in particular the sulfated
      PGs, was highly accentuated in the kidneys of the Hx group compared to the
      controls. Also, a remarkably increased [35S]sulfate incorporation was observed in
      the glomerular mesangial cells. The analysis of IGF-IR by specific binding
      studies revealed a decreased concentration of the receptors, but an increased IGF
      I-binding affinity, the latter of which probably contributed to the IGF-I-induced
      accentuated synthesis of renal glomerular PGs in the Hx group.

PMID- 8275952
TI  - Suppression of follicle-stimulating hormone by the gonadal- and neurosteroid 3
      alpha-hydroxy-4-pregnen-20-one involves actions at the level of the gonadotrope
      membrane/calcium channel.
AB  - We have previously shown that the gonadal- and neurosteroid 3 alpha-hydroxy-4
      pregnen-20-one (3 alpha HP) suppresses FSH release in cultures of anterior
      pituitary cells. We undertook exploration of the mechanisms of this suppression
      by examining the possible sites of 3 alpha HP action in isolated anterior
      pituitary cells of rats. The specific objective of this study was to determine if
      3 alpha HP suppresses FSH by action at the level of the gonadotrope membrane
      and/or calcium channels. Pituitary cells from adult randomly cycling female rats
      were precultured for 72 h and then treated for 4 h with 10 nM GnRH and 0.1 nM 3
      alpha HP with or without Ca2+ channel agonists or antagonist. In other
      experiments, cells were treated with BSA-conjugated 3 alpha HP, progesterone, or
      3 beta HP (the stereoisomer of 3 alpha HP). Levels of FSH were determined by RIA
      in media and cells. GnRH-stimulated FSH release and the total FSH (released plus
      cellular) were significantly suppressed by 3 alpha HP. The Ca2+ ionophore A23187
      induced FSH release and 3 alpha HP significantly suppressed both released and
      total FSH in its presence. In combination with a high dose (100 microM) of the
      dihydropyridine-sensitive Ca2+ channel antagonist nifedipine, 3 alpha HP
      suppressed FSH secretion to a greater extent than the antagonist alone. Cellular
      content of FSH was also decreased by nifedipine (100 microM) and was further
      suppressed in the presence of 3 alpha HP. The phenylalkylamine-sensitive Ca2+
      channel antagonist methoxyverapamil (D600) suppressed GnRH-induced FSH release,
      and 3 alpha HP significantly potentiated the suppression. Released and cellular
      FSH were increased by the dihydropyridine-sensitive agonist BAYK 8644, whereas
      0.1 nM 3 alpha HP suppressed this agonist-induced FSH to a greater extent than
      the maximum dose (100 microM) of nifedipine. In order to test for direct action
      at the level of the gonadotrope membrane, 3 alpha HP was conjugated to BSA (3
      alpha HP-BSA) and administered to cultured pituitary cells. The 3 alpha HP-BSA
      conjugate (but not progesterone-BSA or 3 beta HP-BSA) significantly suppressed
      release of FSH. The results of the study suggest that 3 alpha HP may be
      interacting with the Ca2+ channel component of the GnRH signal transduction
      mechanism; in addition, 3 alpha HP may also suppress FSH release (and possibly
      synthesis) through direct action at the level of the gonadotrope membrane.

PMID- 8275953
TI  - Suppression in gonadotropes of gonadotropin-releasing hormone-stimulated follicle
      stimulating hormone release by the gonadal- and neurosteroid 3 alpha-hydroxy-4
      pregnen-20-one involves cytosolic calcium.
AB  - The gonadal- and neurosteroid 3 alpha-hydroxy-4-pregnen-20-one (3 alpha HP)
      suppresses FSH release in cultures of anterior pituitary cells. In a previous
      report, we showed that this suppression is achieved at least in part by an
      interaction at the plasma membrane level. We undertook to examine the possible
      interaction of 3 alpha HP at the level of intracellular Ca2+. Anterior pituitary
      cells from adult randomly cycling female rats were treated for 4 h with 10 nM
      GnRH and 0.1 nM 3 alpha HP with or without protein kinase C activator (SC10),
      antagonist (H-7), intracellular Ca2+ chelator (TMB-8), and intracellular Ca2+
      mobilizer (glutamate), and with or without EGTA and Ca2+ in the medium. FSH
      content in media and cells was determined by RIA. The protein kinase C (PKC)
      activator, SC10, increased basal levels of secreted FSH. 3 alpha HP suppressed (P
      < 0.05) SC10-stimulated basal FSH release. The PKC inhibitor, H7, decreased GnRH
      induced FSH release; FSH was further suppressed (P < 0.05) by 3 alpha HP in the
      presence of H7. These results were interpreted to indicate that 3 alpha HP may
      act in part at the level of PKC and also at another site(s). The intracellular
      Ca2+ chelator, TMB-8, suppressed released and cellular GnRH-stimulated FSH to the
      same extent as 3 alpha HP; FSH was not further decreased by 3 alpha HP in the
      presence of TMB-8. 3 alpha HP suppressed glutamate-stimulated FSH release in
      Ca(2+)-free medium (P < 0.01). Moreover, GnRH-induced release of FSH was
      suppressed to the same degree by 10(-10) M 3 alpha HP as by 10(-4) M EGTA. In
      pituitary cell suspensions, the GnRH-induced [Ca2+]i elevations were
      significantly (P < 0.05) attenuated by 3 alpha HP. From these and previous
      results, a model is proposed for the action of 3 alpha HP. The model suggests
      that 3 alpha HP may interact with gonadotropes at the level of the PKC cell
      signaling pathway and intracellular Ca2+ mobilization, in addition to the plasma
      membrane/calcium channel. The interaction effects a decrease in intracellular
      Ca2+, leading to decreases in FSH release from those pituitary gonadotropes that
      are responsible for FSH. The consistent decrease in total FSH (released plus
      cellular content) by 3 alpha HP suggests that this neurosteroid may also suppress
      FSH synthesis.

PMID- 8275954
TI  - Expression, purification, and characterization of recombinant rat placental
      lactogen-I: a comparison with the native hormone.
AB  - Rat placental lactogen-I (rPL-I), a member of the PRL/GH gene family, is produced
      by giant cells in the early trophoblast. The small amount of early placental
      tissue has limited the purification of rPL-I from this source. To obtain
      sufficient material for in vitro studies we have used a rPL-I cDNA to express
      this protein in Chinese hamster ovary (CHO) cells and in these studies have
      compared the recombinant protein with the native rPL-I. Using an affinity column
      composed of monoclonal antibody to rPL-I coupled to Sepharose 4B, we have
      purified rPL-I from four sources: 1) recombinant rPL-I produced and secreted in
      rPL-I-transfected CHO cells, 2) nonglycosylated recombinant PL-I produced by
      adding tunicamycin (10 microM/ml medium) to rPL-I-transfected CHO cells, 3)
      native rPL-I secreted by rat choriocarcinoma (RCHO) cells, and 4) serum rPL-I
      isolated from day 12 pregnant rats. Analysis by two-dimensional polyacrylamide
      gel electrophoresis and Western blotting revealed nine subforms with increasing
      mol wt [approximately 34 kilodaltons (kDa)] and acidic pI for recombinant rPL-I
      and RCHO-derived rPL-I. Four major species of lower mol wt (approximately 23 kDa)
      were evident in the nonglycosylated rPL-I, suggesting additional peptide cleavage
      sites. Serum rPL-I contained four additional forms of higher mol wt
      (approximately 37 kDa) and more acidic pI. When analyzed by the Nb2 lymphoma cell
      bioassay, RCHO rPL-I, serum rPL-I, and nonglycosylated rPL-I were equipotent with
      ovine and human PRL. Recombinant rPL-I was 1.5-2.0 times as active as ovine PRL
      in the Nb2 assay. A RIA was established for rPL-I. The variant rPL-Iv, displayed
      nonparallel displacement of [125I]rPL-I from the antibody. There was no cross
      reactivity with other pituitary or placental members of the GH/PRL family.
      Measurement of serum levels of rPL-I by RIA after the injection of recombinant
      rPL-I into adult female Sprague-Dawley rats revealed a half-life of 9 min for the
      recombinant protein compared to 7.8 min for the choriocarcinoma-derived hormone.
      In conclusion, we have shown that although CHO cells will glycosylate the
      recombinant protein differently than normal placental cells, the biological
      properties of our recombinant rPL-I are similar to those of the native, placenta
      cell-derived hormone.

PMID- 8275955
TI  - Follicle-stimulating hormone (FSH) increases FSH receptor messenger ribonucleic
      acid while decreasing FSH binding in cultured porcine granulosa cells.
AB  - The goal of the present studies was to compare direct effects of porcine FSH
      (pFSH) on [125I]pFSH-binding sites with effects of pFSH on FSH receptor mRNA in
      cultured porcine granulosa cells. Cells from immature follicles were cultured on
      laminin-coated plates in serum-free medium for up to 6 days in the absence or
      presence of pFSH (1-100 ng/ml) or cholera toxin (0.04-400 ng/ml), which activates
      adenylyl cyclase independently of the FSH receptor. RRA indicated that [125I]
      pFSH binding to cells cultured without stimulator increased more than 10-fold
      with time in culture. Addition of pFSH to cultures resulted in a dose-dependent
      decrease in binding, assessed after removal of bound pFSH. Equilibrium saturation
      binding analysis indicated that pFSH (10 ng/ml) caused a 39% decrease in binding
      sites in cells cultured for 6 days. At the same time, pFSH increased progesterone
      production 9.5-fold. Cholera toxin (4 ng/ml) increased [125I]pFSH binding 110%
      and progesterone production 8.9-fold. Northern hybridization analysis of cultured
      granulosa cell mRNA using a porcine FSH receptor cDNA revealed three transcripts
      for the FSH receptor [2.2, 3.5, and 4.2 kilobases (kb)], with the major
      transcript being 4.2 kb in length. Addition of either pFSH (10 ng/ml) or cholera
      toxin (10 ng/ml) to cultures of granulosa cells increased the intensity of pFSH
      receptor transcripts compared with control values, with the 4.2-kb message
      remaining predominant. Hybridization with a porcine LH receptor cDNA revealed
      different transcripts (2.4, 4.0, 4.7, 7.0, and 11.0 kb), with the major
      transcript being 4.7 kb in length. Addition of either pFSH or cholera toxin to
      the cultures increased the intensity of all LH receptor transcripts; however,
      cholera toxin was more effective than pFSH. pFSH and cholera toxin increased the
      intensity of each species to different extents, although the 4.7-kb transcript
      remained predominant. These results indicate that exposure to FSH in culture
      results in down-regulation of the FSH receptor. Down-regulation is accompanied by
      increased FSH receptor mRNA levels, suggesting that FSH enhances FSH receptor
      synthesis.

PMID- 8275956
TI  - Estradiol transcriptionally and posttranscriptionally up-regulates thyrotropin
      releasing hormone receptor messenger ribonucleic acid in rat pituitary cells.
AB  - 17 beta-Estradiol (E2) has been shown to up-regulate the binding activity of the
      TRH receptor in rat pituitary cells. In this report, we investigated whether and
      how E2 alters TRH receptor expression at the mRNA level using the oocyte mRNA
      expression system, Northern blot analysis, and nuclear run-on assay. In oocytes
      injected with mRNA from the anterior pituitaries or GH3 cells, a TRH-induced
      45Ca2+ efflux appeared. This efflux was dependent on the amount of TRH and
      injected RNA, and was inhibited by simultaneous addition of chloridazepoxide, an
      antagonist of the TRH receptor. Treatment of GH3 cells with E2 increased TRH
      receptor mRNA activity, as assessed in the oocyte expression system; the E2
      effect became apparent after 3 h of treatment and reached a maximum (3- to 4
      fold) between 6-72 h after addition. Northern blot analysis with a 412-basepair
      cDNA fragment or 3.7-kilobasepair full-length cDNA of the TRH receptor as a probe
      showed that E2 maximally (5-fold) increased the TRH receptor mRNA level of GH3
      cells, with a half-maximal concentration of 0.1 nM after 6 h of treatment. The
      elevated level of mRNA induced by E2 was augmented, rather than impeded, by
      cycloheximide, indicating that ongoing protein synthesis was not required for the
      induction. The rate of transcription of the TRH receptor gene in isolated nuclei
      taken from GH3 cells was increased 3-fold by 2 h of treatment with E2.
      Furthermore, the half-life of the TRH receptor mRNA in GH3 cells was prolonged by
      E2 (from 2.3 to 4.4 h). These results demonstrate that E2 up-regulates the TRH
      receptors of the pituitary cells at the mRNA level by increasing both the
      transcription rate and stability.

PMID- 8275957
TI  - Parathyroid hormone induces sequential c-fos expression in bone cells in vivo: in
      situ localization of its receptor and c-fos messenger ribonucleic acids.
AB  - Localization of PTH/PTH-related peptide (PTH/PTHrP) receptor mRNA and PTH
      induction of c-fos expression were examined in bones of 4-week-old rats by in
      situ hybridization. Receptor transcripts were most highly expressed by growth
      plate chondrocytes from lower proliferating to upper hypertrophic cell layers.
      PTH/PTHrP receptor mRNA also was expressed in osteoblasts as well as in some bone
      marrow stromal cells. Subcutaneous administration of human PTH-(1-84) (225
      micrograms/kg) induced rapid, transient, and sequential expression of the
      protooncogene c-fos mRNA in cells in bone. Osteoblasts and chondrocytes
      expressing PTH/PTHrP receptor transcripts as well as some stromal cells expressed
      c-fos mRNA first (15-60 min), followed by transient expression in the majority of
      stromal cells and in osteoclasts (1-2 h). Delayed and transient induction of c
      fos in cells with few or no detectable receptor transcripts suggests that PTH
      acts indirectly on stromal cells and osteoclasts by either stimulating
      osteoblasts to secrete a substance(s) that acts locally and/or inducing changes
      in cell-cell contacts between osteoblasts and adjacent cells.

PMID- 8275958
TI  - Regulation of parathyroid hormone (PTH)/PTH-related peptide receptor messenger
      ribonucleic acid by glucocorticoids and PTH in ROS 17/2.8 and OK cells.
AB  - To study mechanisms controlling the expression of PTH/PTH-related peptide (PTHrP)
      receptors in ROS 17/2.8 and OK cells, we investigated the regulation of PTH/PTHrP
      receptor availability and receptor mRNA levels by glucocorticoids and PTH.
      Treatment of ROS 17/2.8 cells with dexamethasone (1 microM) for 2, 4, and 6 days
      increased specific binding of PTH to 148 +/- 12%, 203 +/- 10%, and 344 +/- 9%
      (mean +/- SD), respectively, compared to that in untreated control cells. PTH
      stimulated cAMP accumulation also increased with dexamethasone treatment (1
      microM) from 230 +/- 15%, 382 +/- 9%, and 820 +/- 9% after 2, 4 and 6 days,
      respectively, compared to that in untreated cells. Treatment of ROS 17/2.8 cells
      with [Nle8,Nle18,Tyr34]bovine PTH-(1-34) amide (NlePTH; 100 nM) alone or together
      with dexamethasone (1 microM), however, markedly decreased PTH binding and PTH
      stimulated cAMP accumulation. Northern blot analysis showed that dexamethasone
      dramatically increased steady state levels of PTH/PTHrP receptor mRNA in a time-
      and dose-dependent manner, which did not occur when NlePTH (100 nM) was added
      concomitantly to the cultures. As previously reported, daily NlePTH treatment of
      ROS 17/2.8 cells reduced PTH/PTHrP receptor availability and PTH-stimulated cAMP
      accumulation markedly within 2 days, which remained at these low levels during
      continued PTH treatment. In contrast, the identical treatment reduced steady
      state levels of PTH/PTHrP receptor mRNA in ROS 17/2.8 transiently and to only a
      slight extent, which then returned to pretreatment levels. Treatment of OK cells
      with NlePTH (100 nM) for 1, 2, and 4 days decreased PTH binding to 56 +/- 6%, 44
      +/- 4%, and 64 +/- 4% (mean +/- SD) and PTH-stimulated cAMP accumulation to 42 +/
      6%, 19 +/- 4%, and 21 +/- 3% (mean +/- SD), respectively, compared to values in
      untreated control cells. The same treatment, however, had no significant effect
      on steady state levels of PTH/PTHrP receptor transcripts. In contrast to its
      effects in ROS 17/2.8 cells, dexamethasone (1 microM) treatment of OK cells for 1
      4 days did not affect PTH binding, nor did it significantly affect steady state
      levels of PTH/PTHrP receptor mRNA, although the latter was slightly lowered by
      dexamethasone treatment. PTH-stimulated cAMP accumulation was unchanged after 1
      day treatment with dexamethasone and modestly rose to 142 +/- 4% of the control
      value by day 4 of glucocorticoid exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8275959
TI  - Interleukin-1 beta stimulates interleukin-6 production in placental villous core
      mesenchymal cells.
AB  - Interleukin-6 (IL-6) is a pleiotropic mediator of immune function and a growth
      factor for a variety of hematopoietic cell types. Because IL-1 beta is known to
      induce IL-6 production in nonplacental mesenchymal cells and is locally produced
      by maternal decidua, this study was designed to determine whether IL-1 beta could
      regulate IL-6 production by second trimester placental villous core mesenchymal
      cells (VCMC) in vitro. VCMC were prepared for culture by enzymatic digestion of
      placentas (14-20 weeks gestation; n = 7). Immunohistochemistry performed on the
      confluent cells demonstrated that more than 95% of the cells had a fibroblast
      like morphology and were vimentin positive, less than 5% were leukocyte common
      antigen (CA-45) positive, and no trophoblast contamination was demonstrated by
      the lack of cytokeratin staining. In dose-response experiments, a specific dose
      response induction of IL-6 mRNA expression and IL-6-immunoreactive protein
      production by IL-1 beta was demonstrated; this was first seen at 100 pg/ml IL-1
      beta [455 +/- 191 ng/ml (+/- SEM); controls, 42 +/- 16 ng/ml; P < 0.05]. In time
      course studies, the addition of 10 ng/ml IL-1 beta significantly increased IL-6
      production rates; this was first seen at 8 h of culture and increased in a linear
      fashion up to 48 h. At 48 h of culture, IL-6 levels were 17 times higher in
      treated VCMC (861 +/- 179 ng/ml) compared to those in nontreated VCMC (51 +/- 14
      ng/ml). In summary, IL-1 beta stimulates VCMC IL-6 production in a specific dose-
      and time-dependent manner. From these results, we conclude that VCMC are an
      important source of IL-6 in second trimester placenta and that production of
      placental IL-6 be may regulated by decidual IL-1 beta.

PMID- 8275960
TI  - The number and distribution of detectable luteinizing hormone (LH)-releasing
      hormone cell bodies changes in association with the preovulatory LH surge in the
      brains of young but not middle-aged female rats.
AB  - The population of LHRH neurons was examined in young and middle-aged female rats
      at two different time points associated with the LH surge on proestrus. More
      immunopositive LHRH neurons were detected in the brains of young but not middle
      aged females killed on the evening of proestrus (1830-2030 h) compared with those
      killed earlier in the afternoon (1300-1430 h). To facilitate the investigation of
      potential regional differences within the population, sections through the basal
      forebrain were divided into four areas based upon their rostral-caudal position.
      Whereas no change in detectability was observed in the most rostral subset of
      LHRH neurons, more LHRH perikarya were observed at the later compared to the
      earlier time point in the other three areas surveyed in the brains of young
      females. Only the increase observed in sections through the preoptic area,
      however, reached statistical significance. Computer assisted three-dimensional
      reconstruction of all LHRH neurons in sections through the preoptic area revealed
      a marked increase in a subgroup of LHRH neurons in the dorsomedial aspect of this
      region of the population. Changes in detectability of LHRH neurons in association
      with the LH surge suggest that these neurons may be involved in regulating
      preovulatory LH release. Examination of additional time points could reveal
      changes in other subgroups of LHRH neurons as well as significant changes in
      detectability of LHRH neurons in aging brains.

PMID- 8275961
TI  - Lipopolysaccharide induces proenkephalin gene expression in rat lymph nodes and
      adrenal glands.
AB  - The proenkephalin gene encodes a family of neuropeptides that was originally
      identified in brain tissue and adrenal glands. Recently, it was shown that
      proenkephalin is also expressed in cultured lymphoid cells. To elucidate the
      physiological significance of this expression, we examined the in vivo expression
      of proenkephalin in lymphoid tissues. We show here that exposing rats to the
      endotoxin lipopolysaccharide induces an intense and transient expression of
      proenkephalin in adrenal glands and lymph nodes. By using combined in situ
      hybridization and immunohistochemistry on tissue slices, we identified
      proenkephalin expression in macrophages located within the lymph nodes and in
      chromaffin cells within the adrenal glands. This in vivo expression of
      proenkephalin was enhanced by adrenaline. The present observations demonstrate
      that the immune system is a site of significant expression of proenkephalin and
      provide a basis for neuroimmune interactions.

PMID- 8275962
TI  - The effect of the nonselective opioid antagonist diprenorphine on vasopressin
      secretion in the rat.
AB  - Although endogenous opioids are thought to be involved in the regulation of
      vasopressin secretion, their precise role is unclear. We studied the effect of
      the potent nonselective opioid antagonist diprenorphine on the vasopressin
      response to osmotic (hypertonic saline, ip), hypovolemic (polyethylene glycol,
      ip), and hypotensive (sodium nitroprusside, sc) stimuli in male rats. We found
      that diprenorphine sc produced a time- and dose-dependent inhibition of the
      plasma vasopressin response to the hypovolemic stimulus. This inhibition was
      greatest 30 min after injection of the drug, but lasted for at least 4 h, was
      evident at doses as low as 0.0022 mumol/kg, and reached a maximum of about 85% of
      the stimulated control at a dose of 2.2 mumol/kg. Diprenorphine also inhibited
      the vasopressin response to an osmotic or a hypotensive stimulus, but the effect
      was less complete (approximately 50%), required 100-fold higher doses of the
      drug, and appeared to be bimodal. The potent kappa 1-selective opioid agonist U
      50,488H also suppressed the vasopressin response to these stimuli, but the effect
      was not selective for hypovolemia, and the doses required (0.135-13.5 mumol/kg)
      were about 10- to 100-fold higher than those of diprenorphine. We postulate,
      therefore, that diprenorphine potently and preferentially inhibits the
      vasopressin response to an acute hypovolemic stimulus by antagonizing the effect
      of some endogenous opioidergic system critical in the volume control system.

PMID- 8275963
TI  - Histamine stimulates c-fos expression in hypothalamic vasopressin-, oxytocin-,
      and corticotropin-releasing hormone-containing neurons.
AB  - The stimulatory action of centrally administered histamine (HA) on secretion of
      the anterior pituitary hormones ACTH, beta-endorphin, and PRL is indirect, and
      previous studies have suggested that hypothalamic neurons containing CRH,
      arginine vasopressin (AVP), and oxytocin (OT) are involved in this response. We
      studied the effect of HA on neuronal activation in the hypothalamus by
      investigating the expression of c-fos, which is a protooncogene activated early
      when neurons are stimulated. The expression of c-fos was evaluated by detection
      of c-fos immunoreactivity (c-fos-IR) using immunohistochemistry and by
      measurement of c-fos mRNA using in situ hybridization techniques. In addition,
      the identity of the HA-stimulated neurons was investigated by dual antigen
      immunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons showing
      increased c-fos expression. HA (270 nmol) infused intracerebroventricularly
      increased c-fos-IR in the hypothalamus, especially in the periventricular
      hypothalamic areas and certain hypothalamic nuclei, including the paraventricular
      nucleus (PVN) and supraoptic nucleus (SON). c-fos-immunoreactive nuclei were
      observed throughout the SON, whereas in the PVN, c-fos-IR was particularly
      pronounced in the subnuclei known to contain AVP, OT, and CRH neurons. Double
      labeling experiments confirmed that c-fos was expressed in AVP-, OT-, and CRH
      immunoreactive as well as other neurons. In addition, HA
      intracerebroventricularly induced a moderate expression of c-fos-IR in the
      arcuate nucleus. In situ hybridization showed increased levels of c-fos mRNA in
      both the PVN and SON after HA infusion. We conclude that HA-induced secretion of
      ACTH, beta-endorphin, and PRL may be mediated via activation of hypothalamic AVP,
      OT, and CRH neurons.

PMID- 8275964
TI  - Characterization and localization of gonadotropin-releasing hormone receptors in
      the adult female sea lamprey, Petromyzon marinus.
AB  - Quantitative in vitro autoradiography was used to characterize and localize
      putative GnRH receptors in the anterior pituitary of the adult female sea
      lamprey, Petromyzon marinus. Pituitaries were sectioned at 20 microns and
      incubated for 3 h at 4 C with DAla6,Pro9 NEt mammalian GnRH as both the labeled
      and unlabeled ligand. Scatchard analysis revealed two classes of high affinity
      binding sites with Kds of 1.5 x 10(-12) M and 5 x 10(-9) M. Binding to the GnRH
      receptors was saturable, reversible, tissue specific, and time and temperature
      dependent. Displacement studies showed that labeled peptide could be displaced by
      chicken GnRH-I, chicken GnRH-II, synthetic mammal, salmon, lamprey GnRH-I,
      lamprey GnRH-III, DAla6,Pro9 NEt mammalian GnRH and DPhe2,6,Pro3 lamprey GnRH.
      The proximal pars distalis region of the anterior pituitary contained most of the
      GnRH binding sites with slight binding in the rostral pars distalis. These data
      provide direct evidence of GnRH activity on the Agnathan pituitary and are the
      first to demonstrate that a vertebrate pituitary contains two high affinity
      binding sites for GnRH.

PMID- 8275965
TI  - A role for nitric oxide in the regulated expression of the 25-hydroxy-vitamin D-1
      hydroxylation reaction in the chick myelomonocytic cell line HD-11.
AB  - We have recently described the existence of a cytochrome P450-associated,
      mitochondrial-based 25-hydroxyvitamin D (25-OHD)-1-hydroxylation reaction in the
      chick macrophage-like cell line HD-11. Considering that this reaction is
      regulated by the same set of factors (ie. interferon-gamma, lipopolysaccharide,
      and glucocorticoids) that modulate expression of the macrophage nitric oxide
      synthase (mac NOS), we investigated the possibility that endogenous nitric oxide
      (NO) production may be linked to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D) synthesis
      by HD-11 cells in vitro. To test this hypothesis we investigated the effects
      excluding from the extracellular medium the essential amino acid L-arginine,
      substrate for endogenous NO production, on the basal and stimulated expression of
      the HD-11 cell 25-OHD-1-hydroxylation reaction. Depletion of L-arginine from the
      extracellular medium for as little as 6 h resulted in a significant decrease (p <
      0.02) in basal 1,25-(OH)2D synthesis; after 15 h in an L-arginine-free
      environment hormone production was reduced to < 10% of basal levels without any
      adverse affect on cell viability. Reintroduction of L-arginine, but not D
      arginine, into the extracellular medium restored 1,25-(OH)2D3 synthetic capacity
      fully if done after < or = 6 h of incubation in the absence of L-arginine.
      Competitive inhibition of NOS with Nw-nitro-L-arginine methyl ester (p < 0.002)
      and Nw-nitro-L-arginine (p < 0.02) significantly inhibited 1,25-(OH)2D synthesis,
      indicating that macrophage NO generating capacity is functionally linked to
      endogenous synthesis of the active vitamin D metabolite.

PMID- 8275966
TI  - Excessive stimulation is bad, so desensitization is ubiquitous.

PMID- 8275967
TI  - Innervation of the rat anterior and neurointermediate pituitary visualized by
      immunocytochemistry for the growth-associated protein GAP-43.
AB  - Immunocytochemical localization of the neuronal growth associated protein GAP-43
      revealed a dense axonal plexus throughout the neurointermediate lobe of the rat
      pituitary. These axons were fine, presumably monoaminergic fibers, whereas
      magnocellular neurosecretory axons did not appear to contain detectable GAP-43.
      These experiments also revealed the presence of an extensive nerve plexus within
      the anterior lobe. Fine beaded fibers were present throughout the parenchyma of
      the anterior lobe, and punctate staining suggestive of nerve terminals was seen
      surrounding numerous endocrine cells. Nerve fibers did not appear to cross
      directly between the intermediate and anterior lobes, but rather entered the
      anterior lobe directly from its margins or in association with blood vessels.
      Preabsorption of antisera with GAP-43 purified from neonatal rat brain completely
      eliminated immunoreactivity. These findings confirm the existence of a direct
      innervation of the anterior pituitary of the rat; moreover, the presence of GAP
      43 in these fibers suggests that they may be capable of growth and terminal
      reorganization in the adult animal.

PMID- 8275968
TI  - The protein tyrosine phosphatase inhibitor, pervanadate, is a powerful
      antidiabetic agent in streptozotocin-treated diabetic rats.
AB  - The effect of pervanadate, a potent insulinomimetic agent that inhibits insulin
      receptor dephosphorylation in vitro, is now assessed in vivo. A single i.p.
      administration of pervanadate at concentrations as low as 700 micrograms
      vanadium/kg body wt markedly lowered blood glucose levels in streptozotocin
      induced diabetic rats from 430 +/- 28 to 212 +/- 30 mg/100 ml within 3 h. A
      decrease was already observed half hour after treatment, continued in
      accelerating fashion to the 3rd h, and persisted for at least 24 h. The initial
      hyperglycemia reoccurred on the second day and remained thereafter. In comparable
      fashion, pervanadate decreased the blood glucose levels of control healthy rats,
      treated identically. Within this period body wt was not significantly altered in
      either group. This data indicate that rapid and efficient management of glucose
      homeostasis is achieved via inhibiting receptor dephosphorylation. This
      observation may lead to a new therapeutic approach of protein tyrosine
      phosphatase inhibition for future treatment of diabetes in general, and in
      insulin resistant states in particular.

PMID- 8275969
TI  - The effect of selective opioid antagonists on vasopressin secretion in the rat.
AB  - We have shown previously that the nonselective opioid antagonist diprenorphine
      inhibits the vasopressin response to an acute hypovolemic stimulus in rats. To
      elucidate the type of endogenous opioid receptor at which this inhibition occurs,
      we investigated whether more selective antagonists, administered alone or in
      combination with diprenorphine, also inhibited the vasopressin response to
      hypovolemia induced by ip injection of polyethylene glycol. We found that the
      rise in plasma vasopressin was inhibited by the kappa-antagonist Mr 2266 BS at
      doses 30- to 300-fold higher than those of diprenorphine. Over the same dose
      range (0.003-100 mumol/kg), the kappa 1-selective antagonist norbinaltorphimine
      and the mu-selective antagonist naloxone had no effect or enhanced the
      vasopressin response, whereas the delta-antagonist ICI 154,129 had no effect. By
      augmenting the vasopressin response to hypovolemia, higher doses of naloxone or
      nor-binaltorphimine offset the inhibitory effect of concurrently administered
      diprenorphine. Mr 2266 BS did not facilitate, inhibit, or offset the action of
      diprenorphine. The results support the hypothesis that the inhibition of
      vasopressin by diprenorphine is due to antagonism of an opioid receptor and
      suggest that it is one of the recently discovered kappa-subtypes. They also
      suggest that the vasopressin response to acute hypovolemia is normally restrained
      by simultaneous activation of a distinct inhibitory pathway that is blocked by
      kappa 1- or mu-antagonists.

PMID- 8275970
TI  - Physiological relevance of tumor necrosis factor in mediating macrophage-Leydig
      cell interactions.
AB  - Previously, we reported that testicular macrophages constitutively release tumor
      necrosis factor (TNF) in vitro and are unresponsive to bacterial endotoxins
      [lipopolysaccharides (LPS)]. These properties are not typical of other tissue
      macrophages. The goals of the present study were, therefore, to establish 1) if
      testicular macrophages also release TNF in vivo, and 2) if secretion of TNF in
      vitro is influenced by the isolation procedure. In vivo TNF production was
      assessed by assaying testicular interstitial fluid for TNF. Using the L929
      cytotoxicity assay for TNF, we found that interstitial fluid contained a
      cytotoxic factor(s), but this bioactivity was not due to either authentic TNF or
      a TNF-like molecule acting through the TNF receptor. This was established by
      showing that 1) antibodies to TNF alpha and -beta could not neutralize
      interstitial fluid cytotoxicity; 2) interstitial fluid was cytotoxic to TNF
      resistant L929 cells; and 3) there was no detectable TNF immunoreactivity in
      interstitial fluid, as measured by enzyme-linked immunosorbent assay. Therefore,
      we evaluated whether the release of TNF in vitro was induced by the isolation
      procedure, particularly by collagenase, which is used to free interstitial cells.
      Testicular macrophages obtained without the use of collagenase (agitation of
      testes in buffer) did not release TNF, but responded to the TNF-releasing effect
      of LPS. Exposure of peritoneal macrophages to collagenase resulted in
      constitutive TNF release in vitro and lack of responsiveness to LPS. There was no
      evidence that a non-TNF cytotoxic factor was released in the conditioned medium
      by any macrophage preparation. Taken together, our findings show that testicular
      macrophages do not constitutively release TNF, and collagenase has a significant
      activating effect on macrophages. Testicular macrophages will, however, release
      TNF when exposed to LPS, indicating that TNF could be a paracrine regulator of
      testicular steroidogenesis under pathological conditions.

PMID- 8275971
TI  - Evidence that a leukocyte type of 12-lipoxygenase is expressed and regulated by
      angiotensin II in human adrenal glomerulosa cells.
AB  - The 12-lipoxygenase (LO) pathway of arachidonic acid plays an important role in
      angiotensin II (AII)-mediated aldosterone synthesis. Several distinct isoforms of
      12-LO have been cloned. However, in humans only the platelet form of 12-LO has
      been reported to be present. Western immunoblotting analysis in cultured human
      adrenal glomerulosa cells using polyclonal antibodies to porcine leukocyte 12-LO
      enzyme or peptide showed a specific 72-kilodalton band, which is identical to the
      molecular size of the porcine leukocyte form of 12-LO. In addition, AII (10(-7))
      increased the intensity of the 72-kilodalton band nearly 2-fold over basal. In
      situ hybridization analysis indicated a strong positive reaction with the porcine
      leukocyte type of 12-LO antisense riboprobe in the zona glomerulosa of the
      adrenal cortex. The 12-LO probe also recognized a near 4-kilobase messenger RNA
      (mRNA) from human glomerulosa cells in Northern blots. Since the leukocyte type
      of 12-LO is highly homologous to human 15-LO, a reverse transcriptase and
      polymerase chain reaction was used to analyze the specific type of 12-LO mRNA in
      human cells. The mRNA for a porcine leukocyte type of 12-LO was detected in human
      adrenal glomerulosa cells, and the level of 12-LO transcripts was increased
      approximately 60-fold by AII (10(-7) M). The leukocyte type of 12-LO also was
      detected in human monocyte-like U937 cells, but not in IM-9 lymphocytes or human
      erythroleukemia cells. These results suggest that human adrenal glomerulosa cells
      and human monocyte-like U937 cells express a 12-LO which has immunological and
      molecular biological characteristics similar to the porcine leukocyte 12-LO.

PMID- 8275972
TI  - Involvement of protein kinase-C, calpains, and calpastatin in prostaglandin F2
      alpha-induced oxytocin secretion from the bovine corpus luteum.
AB  - An experiment was conducted to determine whether prostaglandin F2 alpha (PGF2
      alpha)-induced secretion of oxytocin (OT) by the bovine corpus luteum (CL) was
      associated with changes in the activities of protein kinase-C (PKC), calpains,
      and calpastatin. On day 8 of the estrous cycle (estrus = day 0), beef heifers
      were restrained and given a 500-micrograms iv injection of cloprostenol, a PGF2
      alpha analog. Corpora lutea were surgically removed from beef heifers 0, 2, 7.5,
      or 30 min (n = 4 animals/time period) after cloprostenol injection. Blood samples
      were collected before injection and at frequent intervals after injection.
      Distribution of PKC activity in cytosol and membrane fractions and activities of
      microcalpain, millicalpain, and calpastatin were determined for all CL. OT was
      measured in plasma and tissue by RIA. Relative to mean plasma levels of OT at
      time zero (85 +/- 7 pg/ml), peak plasma levels occurred between 1.5-10 min (270
      +/- 36 pg/ml) for all animals. The mean luteal concentration of OT was greater at
      0, 2, and 7.5 min (145 +/- 27, 232 +/- 82 and 269 +/- 115 ng/g, respectively)
      than at 30 min (93 +/- 33), but differences in tissue OT over time were not
      significant (P > 0.05). PKC activities (percentage over nonactivated control
      values) in the membrane or cytosolic fractions did not differ significantly among
      the times of CL removal; however, membrane PKC activity was positively correlated
      with the plasma OT level at the time of CL removal (r = 0.82; P < 0.0025). Luteal
      millicalpain activity was approximately twice that of microcalpain at each time
      point (P < 0.001), although the activities of the individual calpains over time
      after PGF2 alpha injection did not change. Calpastatin activity was significantly
      higher at 30 min (515 +/- 28 U/g tissue) than at 0, 2, or 7.5 min (373 +/- 26,
      423 +/- 26, and 426 +/- 24 U/g tissue, respectively). PKC activity in the
      membrane appears to be positively correlated with OT secretion from the bovine
      CL, and increased calpastatin activity after PGF2 alpha injection may inhibit
      calpains present in the CL, thereby maintaining an active pool of PKC.

PMID- 8275973
TI  - Essential role of endogenous estrogen in directly stimulating mammary growth
      demonstrated by implants containing pure antiestrogens.
AB  - The mammogenic actions of estrogen, although undisputed, lack definition due to
      uncertainties concerning the relative importance of systemic vs. local actions of
      the hormone. In addition to its well known, indirect effects on mammary tissue
      through pituitary intermediaries such as PRL and GH, recent evidence points to,
      but does not prove, direct estrogen action on mammary targets. The ability of
      exogenous estrogen to directly and locally stimulate mammary growth in vivo was
      previously shown in endocrine-ablated animals using small plastic pellets
      containing estradiol. The more important question of whether the direct action of
      endogenous estrogen is required for normal mammary growth and morphogenesis in
      the endocrine-intact animal is now investigated using direct-acting, slow-release
      plastic implants containing pure antiestrogens (antiestrogens with no estrogenic
      properties) inserted into the growth region of mammary glands. Local growth
      inhibition only in the immediate vicinity of the implants and not in other glands
      in the same mouse demonstrated the requirement of mammary tissues for endogenous,
      locally acting estrogen. Local actions of antiestrogens on ducts mimicked the
      ovariectomy-induced loss of systemic estrogen with respect to time course and
      morphology, with complete inhibition of ductal growth in 14 days. A second
      effect, in which locally acting antiestrogens simplified the pattern of ductal
      branching, was observed in both immature and mature animals. Two distinct
      mitogenic pathways, one governing ductal elongation and the other ductal
      maintenance, were thus affected. The inhibitory effects of antiestrogen treatment
      were fully reversible and not accompanied by obvious cytotoxicity. We conclude
      from these studies of localized estrogen receptor blockade that with respect to
      ductal mammogenesis, the action of estrogen is direct (acting at the level of the
      gland itself) and not primarily through the stimulation of pituitary mammogens.

PMID- 8275974
TI  - Protein kinase A regulates nicotinic cholinergic receptors and subunit messenger
      ribonucleic acids in PC 12 cells.
AB  - To delineate mechanisms regulating the expression of neuronal nicotinic
      cholinergic receptors (nAcChRs), we studied the cAMP-dependent second messenger
      system. PC 12 cells were grown in (Bu)2cAMP (0.001-1.0 mM) or vehicle for 7 days,
      and specific [3H] nicotine binding was measured. (Bu)2cAMP (0.1 mM) increased
      specific binding 2- and 4-fold at 3 and 7 days, respectively, whereas 1.0 mM
      enhanced binding 4-fold at both time intervals. Cells grown in 8-bromo-cAMP (1.0
      mM) showed a 2-fold increase in [3H]nicotine binding at 3 days. Forskolin (10-100
      microM), in combination with isobutyl-methylxanthine (1.0 mM), enhanced
      [3H]nicotine binding 2- to 3-fold at 7 days; forskolin or isobutyl-methylxanthine
      alone had no effect. Specific [3H] nicotine binding to PC 12 cell mutants
      (A126.1B2 and A123.7), deficient in cAMP-responsive protein kinase A types I and
      II, were unaffected by (Bu)2cAMP. Northern gel analysis of nAcChR subunit
      messenger RNAs showed that the alpha-3, alpha-5, and beta-4 subunits were
      significantly decreased by (Bu)2cAMP at 4 h. However, (Bu)2cAMP caused an
      increase in the beta-2 messenger RNA transcript at 4 h, which returned to
      baseline by 24 h. These studies indicate that the cAMP-protein kinase A system
      regulates expression of nAcChR by PC 12 cells. These studies also suggest that
      enhancement of [3H]nicotine binding by activated protein kinase A may not involve
      synthesis of new receptor subunit proteins.

PMID- 8275975
TI  - Alpha-melanocyte-stimulating hormone and N-acetyl-beta-endorphin
      immunoreactivities are localized in the human pituitary but are not restricted to
      the zona intermedia.
AB  - The adult human pituitary lacks a well defined intermediate lobe, and it is
      uncertain whether the POMC cells that remain in the zona intermedia represent
      melanotropes or corticotropes. In the present study, we investigated whether the
      N-acetylated beta-endorphin- and alpha-MSH-related peptides that are
      characteristically produced by melanotropes in the rat and other species are
      localized in the human pituitary. Sequential gel filtration and ion exchange HPLC
      analysis revealed that small amounts of alpha-N-acetyl-beta-endorphin-(1-31), as
      well as beta-endorphin-(1-27) and beta-endorphin-(1-26), were detectable in human
      pituitary extracts, although beta-endorphin-(1-31) was clearly the major form.
      Consistent with this analysis, low levels of alpha-MSH, but not N,O-diacetyl
      alpha-MSH, were identified by reverse-phase HPLC, although again, the desacetyl
      form of alpha-MSH predominated. Immunohistochemistry revealed that N-acetyl-beta
      endorphin immunoreactivity was colocalized with ACTH and beta-endorphin in a
      subpopulation of zona intermedia cells. Unexpectedly, immunoreactive N-acetyl
      beta-endorphin was also observed in a comparable proportion of corticotropes
      dispersed throughout the anterior lobe. alpha-MSH immunoreactivity was similarly
      distributed. These results indicate that N-acetylation is not restricted to the
      zona intermedia, suggesting that the strict dichotomy between corticotrope and
      melanotrope POMC processing observed in the rat and other species does not extend
      to the human pituitary.

PMID- 8275976
TI  - The prevalence and incidence of convulsive disorders in children.
AB  - Each year, about 150,000 children and adolescents in the United States will come
      to medical attention for evaluation of a newly occurring seizure disorder of some
      type. Between 2% and 4% of all children in Europe and the United States
      experience at least one convulsion associated with a febrile illness before the
      age of 5 years. The cumulative incidence of febrile convulsions among children
      ranges from about 1% in China to more than 8% in Japan and 14% in Guam. The peak
      incidence of a first febrile convulsion occurs in the second year of life.
      Between 0.5% and 1% of children and adolescents experience a seizure associated
      with other acute metabolic or neurologic insults; most of these occur in the
      neonatal period. The incidence of epilepsy (recurrent unprovoked seizures) in
      children and adolescents seems relatively consistent across all populations
      studied, ranging from 50 to 100/100,000. The highest incidence of epilepsy is in
      the first year of life. West syndrome accounts for about 2% of all childhood
      epilepsy. Lennox-Gastaut syndrome for 1-2%, childhood absence epilepsy
      (pyknolepsy) for 10-15%, juvenile myoclonic epilepsy for 5%, and idiopathic
      localization-related epilepsy for 10%. Between 0.5 and 1% of children experience
      a nonrecurrent, single, unprovoked convulsive episode. Following are the
      estimated numbers of children and adolescents with newly diagnosed convulsive
      disorders in the United States for the year 1990: febrile seizures, 100,000;
      neonatal seizures, 4,000; other provoked seizures, 6,000; single unprovoked
      seizures, 10,000; and epilepsy, 30,000.

PMID- 8275977
TI  - Pharmacologic intervention and treatment of childhood seizure disorders: relative
      efficacy and safety of antiepileptic drugs.
AB  - Four antiepileptic drugs (AEDs) represent > 90% of all AEDs prescribed in the
      United States. The efficacies of the available AEDs are surprisingly similar and
      far from complete, and none is entirely safe. Thus, the incidence of side effects
      is often the determining factor in the choice of AED. Clinical decisions about
      which AED to select should be made on the basis of the combination of efficacy
      and toxicity, expressed as a protective or therapeutic index (TI). Efficacy
      seldom comes without some degree of toxicity, whereas toxicity can occur in the
      absence of any efficacy. As the dose of the AED increases, efficacy can reach a
      plateau but toxicity does not. Complete seizure control should not be the final
      goal of epilepsy treatment; optimal AED therapy is equal to the highest possible
      TI, not necessarily to maximal seizure control. Each AED has a different TI, and
      each has a different TI in every patient. This is confounded further when
      combinations of AED are prescribed.

PMID- 8275978
TI  - Investigational antiepileptic drugs for the treatment of childhood seizure
      disorders: a review of efficacy and safety.
AB  - Pediatric epileptology is very different from adult epileptology. Although some
      epileptic disorders occur in both children and adults (e.g., localization-related
      epilepsy with complex partial seizures and primary generalized epilepsy with
      tonic-clonic seizures), other disorders can be called the catastrophic epilepsies
      of childhood (e.g., infantile spasms and the Lennox-Gastaut syndrome). They
      occur, or at least begin, exclusively in childhood and are often associated with
      mental retardation. Many of these pediatric disorders are notoriously
      unresponsive to currently available antiepileptic drugs (AEDs). Although there
      are undoubtedly many reasons for this, one possible explanation is that the
      methods used to screen potential AEDs use animal models of adult epilepsy. No
      screening program uses an animal model of seizures that begin during development
      and lead to functional decline.

PMID- 8275979
TI  - Prognosis of childhood seizure disorders: present and future.
AB  - The prognoses for seizure disorders have been examined since the beginnings of
      epileptology, and only recently has the realization emerged that, ultimately,
      prognosis depends on causation, which, in turn, determines whether a condition is
      self-limited or progressive. This factor is more important than either mode or
      alacrity of therapeutic intervention. The epilepsies are a series of conditions
      that have the final common path of either increasing cerebral irritability or
      synchronizing normally occurring electrical activity in such a manner that
      seizures result. In turn, some seizure disorders are characterized by secondary
      changes in neuronal synaptogenesis, leading to the development of circuits of
      predilection, which then render the process autonomous. Epileptogenesis has then
      become epilepsy, which is the norm in acquired rather than genetic
      epileptogenesis. An understanding of the basic differences between the primary
      (idiopathic) epilepsies and the secondary (acquired or symptomatic) epilepsies is
      basic to a discussion concerning prognosis and to the development of a definitive
      individualized treatment plan. An elucidation of the genetic factors in
      idiopathic epilepsy and their neurochemical consequences represents a major
      frontier in epileptology.

PMID- 8275980
TI  - Diagnosis of childhood seizure disorders.
AB  - Convulsive epilepsies are generally unmistakable. Absence epilepsies, which are
      easily recognized by the provocation of an episode during hyperventilation and by
      the typical features of the EEG, can be overdiagnosed, especially in the child
      who daydreams in class and has scattered, asymptomatic, epileptogenic EEG
      changes. As in adults, complex partial seizures in children can be difficult to
      distinguish from certain behaviors. Several types of benign childhood epilepsies
      need to be distinguished from the more intractable and lesional childhood
      epilepsies. Two common examples, benign rolandic epilepsy and benign occipital
      epilepsy, can be recognized by their unique EEG changes and clinical features.
      Juvenile myoclonic epilepsy generally does not remit spontaneously but should be
      recognized because it appears to respond to valproate. Some recurrent
      nonepileptic events seen in children can be mistaken for seizures, including
      shuddering attacks, paroxysmal vertigo, breath-holding spells, cardiogenic
      syncope, night terrors, and movement disorders, such as paroxysmal kinesigenic
      choreoathetosis.

PMID- 8275981
TI  - Identification and quantification of pollutants that have the potential to affect
      evolutionary processes.

PMID- 8275982
TI  - Toxicity tests in animals: alternative models.

PMID- 8275983
TI  - The Cheshire cat phenomenon: effects of nonionizing electromagnetic radiation.

PMID- 8275984
TI  - Strategic planning: will it influence the future of environmental health
      research?

PMID- 8275985
TI  - The use of transgenic mice for environmental health research.

PMID- 8275986
TI  - Elemental analysis of renal slices by proton-induced X-ray emission.
AB  - We optimized proton-induced X-ray emission (PIXE) for tissue analysis in a
      toxicity-disposition study. We used cultured rabbit renal slices as the
      biological system to demonstrate the use of PIXE analysis. The renal slices were
      exposed to HgCl2, CdCl2, K2Cr2O7, or NaAsO2 alone or in a mixture. The PIXE
      analysis provides information on concentrations of elements above atomic number
      11, and it is the only analytical technique that can determine 20-30 elements
      nondestructively in a single, small sample (approximately 5 mg) with detection
      limits of 1-5 ppm (dry weight). The renal slices are thin targets that yield X
      ray emission spectra with low backgrounds and high elemental sensitivities. The
      nondestructive nature of PIXE and the ability to simultaneously measure uptake of
      multiple metals and endogenous elements are unique to this methodology.

PMID- 8275987
TI  - Identification of 6-hydroxy-trans,trans-2,4-hexadienoic acid, a novel ring-opened
      urinary metabolite of benzene.
AB  - We studied the in vivo metabolism of benzene in mice to ring-opened compounds
      excreted in urine. Male CD-1 mice were treated intraperitoneally with benzene
      (110-440 mg/kg), [14C]benzene (220 mg/kg) or trans, trans-muconaldehyde (MUC; 4
      mg/kg), a microsomal, hematotoxic metabolite of benzene. Urine, collected over 24
      hr, was extracted and analyzed by HPLC with a diode-array detector and by
      scintillation counting. In addition to trans,trans-muconic acid, previously the
      only known ring-opened urinary benzene metabolite, a new metabolite, 6-hydroxy
      trans,trans-2,4-hexadienoic acid, was detected in urine of mice treated with
      either benzene or MUC. We identified the new metabolite based on coelution of
      metabolites and UV spectral comparison with authentic standards in unmethylated
      and methylated urine extracts. Results presented here are consistent with the
      intermediacy of MUC in the in vivo metabolism of benzene to ring-opened
      metabolites.

PMID- 8275988
TI  - Passive cigarette smoke, coal heating, and respiratory symptoms of nonsmoking
      women in China.
AB  - In this study we evaluated data from a sample of 973 never-smoking women, ages 20
      40, who worked in three similar textile mills in Anhui Province, China. We
      compared prevalence rates of respiratory symptoms across homes with and without
      coal heating and homes with different numbers of smokers. Multiple logistic
      regression models that controlled for age, job title, and mill of employment were
      also estimated. Respiratory symptoms were associated with combined exposure to
      passive cigarette smoke and coal heating. Effects of passive cigarette smoke and
      coal heating on respiratory symptoms appeared to be nearly additive, suggesting a
      dose-response relationship between respiratory symptoms and home indoor air
      pollution from these two sources. The prevalence of chest illness, cough, phlegm,
      and shortness of breath (but not wheeze) was significantly elevated for women
      living in homes with both smokers and coal heating.

PMID- 8275989
TI  - Use of personal measurements for ozone exposure assessment: a pilot study.
AB  - During summer 1991, we collected indoor, outdoor, and personal ozone
      concentration data as well as time-activity data in State College, Pennsylvania.
      These concentrations were measured for 23 children and their homes using passive
      ozone samplers. Outdoor concentrations were also measured at a stationary ambient
      monitoring site. Results from this pilot study demonstrate that fixed-site
      ambient measurements may not adequately represent individual exposures. Outdoor
      ozone concentrations showed substantial spatial variation between rural and
      residential regions. Ignoring this spatial variation by using fixed-site
      measurements to estimate personal exposures can result in an error as high as
      127%. In addition, evidence from our pilot study indicates that ozone
      concentrations of a single indoor microenvironment may not represent those of
      other indoor microenvironments. Personal exposures were significantly correlated
      with both indoor (r = 0.55) and outdoor (r = 0.41) concentrations measured at
      home sites. Multiple regression analyses identified indoor ozone concentrations
      as the most important predictors of personal exposures. However, models based on
      time-weighted indoor and outdoor concentrations explained only 40% of the
      variability in personal exposures. When the model included observations for only
      those participants who spent the majority of their day in or near their homes, an
      R2 of 0.76 resulted when estimates were regressed on measured personal exposures.
      It is evident that contributions from diverse indoor and outdoor
      microenvironments must be considered to estimate personal ozone exposures
      accurately.

PMID- 8275990
TI  - Rat pleural mesothelial cells show damage after exposure to external but not
      internal cigarette smoke.
AB  - The combination of cigarette smoke and high-level occupational asbestos exposure
      produces a synergistic increase in the incidence of lung cancer; however, smoking
      does not affect the incidence of mesothelioma. Here we present the results of
      tests of two theories that have been proposed to explain this phenomenon; namely,
      that pleural mesothelial cells are resistant to cigarette smoke-induced damage
      and that the pleural connective tissue acts as a barrier that prevents smoke from
      reaching the mesothelial cells. To test these hypotheses, excised whole rat lung
      preparations were exposed to either internal (intratracheal) or external (pleural
      surface) smoke. For comparison, additional excised lung preparations were exposed
      to solutions of hydrogen peroxide either externally or intratracheally.
      Mesothelial cells exposed to external smoke showed widespread, dose-dependent
      uptake of Trypan blue. Mesothelial cells did not take up Trypan blue after
      exposure to internal smoke. Bronchial epithelial cells exposed to internal smoke
      did show uptake, but to a lesser degree than externally exposed mesothelial
      cells. Examination by scanning and transmission electron microscopy showed that
      internal smoke did not affect mesothelial cell ultrastructure, whereas external
      smoke produced obvious mesothelial cell damage and mesothelial cell detachment.
      Catalase and deferoxamine, scavengers of active oxygen species, provided
      protection against smoke-induced mesothelial cell injury, but inactivated
      catalase did not. External hydrogen peroxide produced a very similar, dose
      dependent pattern of Trypan blue uptake and ultrastructural changes.
      Intratracheal hydrogen peroxide also damaged mesothelial cells, but the extent of
      damage was always less than with comparable concentrations of external hydrogen
      peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8275991
TI  - Relationship between molecular connectivity and carcinogenic activity: a
      confirmation with a new software program based on graph theory.
AB  - For a database of 826 chemicals tested for carcinogenicity, we fragmented the
      structural formula of the chemicals into all possible contiguous-atom fragments
      with size between two and eight (nonhydrogen) atoms. The fragmentation was
      obtained using a new software program based on graph theory. We used 80% of the
      chemicals as a training set and 20% as a test set. The two sets were obtained by
      random sorting. From the training sets, an average (8 computer runs with
      independently sorted chemicals) of 315 different fragments were significantly (p
      < 0.125) associated with carcinogenicity or lack thereof. Even using this
      relatively low level of statistical significance, 23% of the molecules of the
      test sets lacked significant fragments. For 77% of the molecules of the test
      sets, we used the presence of significant fragments to predict carcinogenicity.
      The average level of accuracy of the predictions in the test sets was 67.5%.
      Chemicals containing only positive fragments were predicted with an accuracy of
      78.7%. The level of accuracy was around 60% for chemicals characterized by
      contradictory fragments or only negative fragments. In a parallel manner, we
      performed eight paired runs in which carcinogenicity was attributed randomly to
      the molecules of the training sets. The fragments generated by these pseudo
      training sets were devoid of any predictivity in the corresponding test sets.
      Using an independent software program, we confirmed (for the complex biological
      endpoint of carcinogenicity) the validity of a structure-activity relationship
      approach of the type proposed by Klopman and Rosenkranz with their CASE program.

PMID- 8275992
TI  - Narcolepsy in animals and man.

PMID- 8275993
TI  - Treatment and pathogenesis of navicular disease ('syndrome') in horses.
AB  - The future directions of navicular disease research are unclear. Often
      researchers investigate only one of the multitude of factors likely to be
      important in understanding the disease. Two exceptions to this is work done by
      Wright in this issue of EVJ and by MacGregor (1988) who compared a number of the
      treatment regimens (e.g. rest, warfarin, isoxsuprine, shoeing with egg bars) and
      found that approximately 75% of the horses improved in their performance. Perhaps
      this percentage of 'recovered' horses from this disease is what can be
      realistically expected, as often horses with navicular disease remain undiagnosed
      until the disease has advanced to the stage where problems exist in the foot or
      to where the conformation-balance of the hoof is irrecoverable. Perhaps the key
      to controlling the disease is prevention by maintaining good overall hoof
      husbandry in a conservative and consistent manner. I would advocate that efforts
      be made to evaluate hoof 'balance' and the validity of the hoof wall-pastern axis
      being parallel, as these are clearly of importance in this debilitating disease.

PMID- 8275994
TI  - A study of 118 cases of navicular disease: clinical features.
AB  - The clinical features are reported from 118 horses (mean age 9.2 years) which
      were diagnosed as suffering from navicular disease using predetermined criteria.
      The animals were used for a variety of purposes and had been lame for periods
      between 1 and 72 months. The majority of cases (84.7%) had been treated using
      various techniques before evaluation. The severity of lameness was related to the
      duration of clinical signs: 78% of horses were bilaterally affected but there was
      no left:right limb predominance. Broken foot/pastern axes were recorded in 75% of
      horses while 45% also exhibited mediolateral foot imbalance. Muscle atrophy was
      recognised in 77% of animals which appeared to be related to limb affliction. The
      cranial phase of the stride was reduced in 38% and caudal phase shortened in 16%
      of horses. These abnormalities were related to the degree of lameness. Flexion of
      the distal joints increased the severity of lameness in 64% of the animals while
      extension was positive in 41% of instances. Turning in the direction of the lame
      limb exacerbated lameness in 95% of horses. Only 11% of animals responded to the
      use of hoof testers and 3% to foot percussion. A range of responses to local
      analgesia of the palmar digital nerves was recorded but 91% (of 49) of animals
      exhibited a positive response to local analgesia of the distal interphalangeal
      joint, and 92% (of 23) of horses responded to local analgesia of the navicular
      bursa.

PMID- 8275995
TI  - A study of 118 cases of navicular disease: radiological features.
AB  - Dorsoproximal-palmarodistal oblique, lateromedial and palmaroproximal
      palmarodistal oblique radiographic projections were used with standard techniques
      to examine 118 horses with clinical signs of navicular disease. All radiological
      features which have previously been reported as significant changes in the
      navicular bones of horses with navicular disease were recorded. Comparisons were
      made between these features in lame limbs and sound limbs in unilaterally lame
      horses and most lame limbs and least lame limbs in bilateral but asymmetrically
      lame animals. Their relationship to the degree of lameness was also analysed. No
      relationships were identified between the characteristics of distal border
      synovial invaginations, flattening and/or thinning of the flexor cortex and limb
      distribution or severity of lameness. Defects in the flexor cortex, proximal
      border remodelling, medullary trabecular disruption and medullary sclerosis
      appeared to be related to limb affliction and severity of lameness while proximal
      border enthesophytes, and poor flexor corticomedullary demarcation presented
      evidence of a relationship to the grade of lameness. Poor flexor corticomedullary
      demarcation and fragmentation of the distal border were related to the severity
      of lameness in bilateral but asymmetrically affected horses. The presence of peri
      articular osteophytes and mineralisation of the flexor digitorum profundus were
      too infrequently recognised to permit meaningful data evaluation.

PMID- 8275996
TI  - A study of 118 cases of navicular disease: treatment by navicular suspensory
      desmotomy.
AB  - The 118 horses diagnosed as suffering from navicular disease by prospective
      criteria were treated by desmotomy of the ligamenta sesamoidea collateralia
      (navicular suspensory desmotomy). Three techniques were used and a standard post
      operative programme was followed with clinical and radiological evaluations at 6
      monthly intervals for periods of 6-36 months after surgery. At 6 and 36 months
      after treatment, 76% and 42.9% of horses were sound respectively. The clinical
      features of age, period of lameness, severity of lameness and angular limb
      deformities adversely affected response to surgery. The presence of flexor cortex
      defects, proximal border enthesophytes, mineralisation of the flexor digitorum
      profundus tendon and medullary sclerosis were also associated with a diminished
      response. There were few (1.7%) changes in the radiological appearance of distal
      border synovial invaginations during the follow-up period. By contrast, the
      majority (67.3%) of flexor cortex defects changed. Other radiological features
      changed at a low frequency but there was no association between radiological
      change and clinical outcome.

PMID- 8275997
TI  - Muscular pathology in equine laryngeal neuropathy.
AB  - Three adductor muscles of the larynx, the cricoarytenoideus lateralis (CAL), the
      arytenoideus transversus (AT) and the ventricularis (Ve), from 36 horses were
      examined histologically. The neurogenic changes seen in each muscle were
      evaluated qualitatively. In addition, in 6 horses with clinical and subclinical
      signs of neurogenic atrophy, measurements of muscle fibre area were performed.
      Neurogenic changes observed in the Ve were less than in CAL and AT. Measurements
      of muscle fibre area also demonstrated that CAL and AT showed a wider range of
      pathological changes than did Ve. The results show that denervation does not
      uniformly affect all adductor muscles of the larynx. On the other hand, the
      appearance in some animals of fibre type grouping in the right AT to the same or
      to a greater extent than in the left AT supports the classification of equine
      laryngeal neuropathy as a distal axonopathy.

PMID- 8275998
TI  - Age-related characteristics of gastric squamous epithelial mucosa in foals.
AB  - Specimens of grossly normal gastric stratified squamous epithelial mucosa
      adjacent to the margo plicatus on the right side and along the greater curvature
      were obtained from 7 foetuses, 10 term foals and 12 foals 2-35 days old. Gastric
      squamous epithelium from the foetuses changed markedly during gestation. At 150
      270 days, the epithelium was 8-10 cells thick, with a single layer of basal
      cells. Epithelial cells were polyhedral and had abundant clear or slightly
      stained cytoplasm. In the 300-day foetus the basal layer was thicker, epithelial
      cells were polyhedral, and there was a flattened 1 cell-thick layer
      superficially. In the 335-day foetus, the epithelial cells were flat and there
      was a superficial layer of keratinised cells, 1-2 cells thick. In term foals, the
      gastric epithelium consisted of 10-12 cell layers, with 4-5 thin layers of
      surface keratin. Epithelial projections (papillae) were either absent or not
      pronounced. The gastric epithelium became thicker with increasing age, including
      increased epithelial cell layers, thickening of the keratinised layers, and more
      pronounced papillae. Desquamation was observed in the keratinised layers of
      gastric squamous epithelium from foals > or = 2 days of age.

PMID- 8275999
TI  - Review of 115 cases of colic in the pregnant mare.
AB  - The medical records of pregnant mares over a 3-year period were reviewed. In all
      cases persistent pain or progressive abdominal distension were the main reason
      for referral. The overall survival rate for the 115 mares treated for colic was
      73.9% (85 cases). The abortion rate was 20.5% in surgical patients (34 cases),
      40% (5 cases) for mares with uterine torsions and 10.8% (46 cases) after medical
      treatment. The total abortion rate was 16.4%. Clinical evidence of endotoxaemia
      was, except for 1 mare, present in all the aborting mares after colic treatment.
      Anaesthesia did not appear to be a problem because abortion occurred in 5/46
      medically treated cases as well as in 9/39 mares treated surgically. Abortion
      occurred in 3 mares that suffered intraoperative hypoxia, but fasting for > 30 h
      did not seem to cause prolonged hypoglycaemia and subsequent abortion.
      Clenbuterol hydrochloride was used as a tocolytic agent in 9 mares with uterine
      displacement, abortus imminens and post-operative uterine torsion and 3 mares
      aborted during treatment.

PMID- 8276000
TI  - A review of cytological specimens from horses with and without clinical signs of
      respiratory disease.
AB  - Thirty-six transtracheal washing (TTW) and 12 bronchoalveolar lavage (BAL)
      specimens collected in clinical practice from horses with and without respiratory
      disease were reviewed. Cytological features were considered in accordance with
      the presenting complaint, clinical signs, clinical diagnoses, microbiological,
      radiographic and/or endoscopic findings, therapy, and response to therapy. The
      trichrome-stained TTW and BAL specimens were useful in interpreting the results
      of concurrent microbiological cultures, and determining whether a condition was
      present based on occurrence of typical cytological features of patterns (e.g.
      probable allergy, chronic obstruction, uncomplicated exercise-induced pulmonary
      haemorrhage), determining pathological/anatomical diagnoses (e.g. bronchitis,
      bronchiolitis and/or alveolitis; presence of metaplasia or dysplasia) and
      possible aetiologies (e.g. allergy, bacterial infection). Review of these cases
      confirmed the practicality of using cytological specimens to evaluate the equine
      respiratory tract; there were few unsatisfactory specimens and no reported
      complications. The importance of cytological evaluation of the equine respiratory
      system was emphasised by the identification of 13 cases in which clinical signs
      were not apparent at physical examination. Sequential collections of cytological
      specimens from foals, young horses before and during early training, and mature
      horses in training may provide more information about the response of the equine
      lung to stresses associated with training and/or common environmental exposures.

PMID- 8276001
TI  - Metabolic response to standardised exercise test in standardbred trotters with
      red cell hypervolaemia.
AB  - Plasma concentrations of lactate, amino acids, ammonia and products of purine
      catabolism were studied before, during and after a standardised incremental
      exercise test in 29 Standardbred trotters admitted to the clinic for exercise
      tolerance testing. According to their red cell volume the horses were divided
      into red cell normovolaemic and red cell hypervolaemic (polycythaemic) groups.
      The exercise-response curve for taurine differed significantly in the two groups,
      whereas all the other amino acids behaved similarly. The [branched-chain amino
      acid]/[alanine] ratio, a proposed indicator for the use of amino acids in
      gluconeogenesis, was at rest significantly higher in the polycythaemic horses.
      Post-exercise concentrations of ammonia and allantoin, both end products of ATP
      breakdown, were lower in the polycythaemic horses. No differences were observed
      in the VLA4 and V200 markers for lactate and heart rate responses to incremental
      exercise, the oxidative capacity of the gluteus medius muscle, the enzyme
      activities or the post-exercise concentration of lactate, uric acid and
      hypoxanthine. It is concluded that horses with red cell hypervolaemia behave in a
      submaximal standardised exercise test on a treadmill in the same way as do red
      cell normovolaemic horses. The results suggest that the rate of amino acid
      utilisation in gluconeogenesis and the ability of amino acids to produce energy
      aerobically may be elevated in polycythaemic horses.

PMID- 8276002
TI  - Training-induced modifications in cardiorespiratory and ventilatory measurements
      in thoroughbred horses.
AB  - The effects of training and detraining on ventilation during a standardised
      exercise test were investigated. Ten healthy Thoroughbred horses underwent 5
      standardised treadmill exercise tests (SET): SET1, at the start of the
      experimental period; SET2, after 3 weeks acclimatisation; SET3, after 3 week of
      aerobic training; SET4 after 3 weeks of anaerobic (i.e. interval) training; and
      SET5, after 3 weeks of detraining. The SETs were carried out in an air
      conditioned laboratory on a treadmill inclined at 6 degrees. Respiratory airflow,
      tidal volume (VT), respiratory frequency (RF) and expired minute volume (VE) were
      obtained using a face mask and 2 ultrasonic pneumotachographs. Peak oxygen uptake
      (VO2 peak) and carbon dioxide production (VCO2 peak) values were calculated on a
      breath-by-breath basis, using a mass spectrometer. Heart rate (HR) was
      continuously measured with a polar horse tester. Oxygen pulse (VO2/HR) and
      ventilatory equivalent for O2 were calculated from the collected data. Venous
      blood was sampled before and after the SET for lactate, pH and haemoglobin
      determinations. The results indicated that trained horses showed significant
      modifications of all values, except VT, RF and VE. This study suggests that, in
      horses, the increase in VO2 induced by training seems to be mainly due to
      cardiovascular and haematological changes rather than to ventilatory changes.
      Consequently, while all the other systems implicated in exercise physiology can
      be efficiently improved and trained, the ventilatory capacity has only limited
      ability to adapt to training.

PMID- 8276003
TI  - Are equine 1 influenza viruses still present in horses?

PMID- 8276004
TI  - Use of ultrasonography to evaluate the degree of ossification of the small tarsal
      bones in 10 foals.

PMID- 8276005
TI  - Passage of unfertilised horse eggs transplanted to pig oviducts.

PMID- 8276006
TI  - Alveolar rhabdomyosarcoma: an unusual cause of lameness in a pony.

PMID- 8276007
TI  - Incarceration of the large colon through the epiploic foramen in a horse.

PMID- 8276008
TI  - Massive iron overload and liver fibrosis resembling haemochromatosis in a racing
      pony.

PMID- 8276009
TI  - Urticarial response during anesthesia in a horse.

PMID- 8276010
TI  - Ocular medulloepithelioma in a thoroughbred.

PMID- 8276011
TI  - Clement A. Smith.

PMID- 8276012
TI  - Contribution to scientific research in paediatrics in The Netherlands: evaluation
      according to subspeciality over a 10-year period.
AB  - The board of the Dutch Paediatric Association requested a survey of the
      scientific research performed in all academic and non-academic paediatric
      hospitals, authorized to train medical doctors in paediatrics in the Netherlands.
      Contributions to the international and the Dutch scientific literature, in the
      form of regular publications, chapters in books, contributions to proceedings and
      Ph.D. theses were counted over two 5-year periods, i.e. 1981-1985 and 1986-1990.
      The quality of publications in the international journals was assessed using the
      average impact factor of the journals over the 10-year period. The number of
      publications in the international literature doubled during the observation
      period 1986-1990 compared to the period 1981-1985. Nevertheless, the quality of
      the publications remained the same. Metabolism, oncology/haematology,
      immunology/infectious diseases and cardiology are the subspecializations in which
      scientific research takes place in four or more academic paediatric hospitals. In
      total, 84 Ph.D. theses were produced in which a paediatrician was either the
      project leader (mostly a professor in paediatrics) or the investigator-in-charge.
      Insight into structure and major research efforts of paediatric hospitals in
      other countries of Europe may lead to exchange of views and, maybe, profitable co
      operation.

PMID- 8276013
TI  - Hyperuricaemia in cyanotic congenital heart disease.
AB  - This study examines the exacerbating factors of hyperuricaemia in patients with
      cyanotic congenital heart disease (CCHD). We studied 59 CCHD patients aged 1
      month-30 years. The following variables were assessed: serum uric acid levels,
      red blood cell count, haemoglobin, hematocrit, partial oxygen pressure and
      arterial oxygen saturation. Uric acid excretion and renal function were also
      measured in ten patients with serum levels of uric acid greater than 8 mg/dl
      (hyperuricaemia group). Serum uric acid level correlated significantly with age
      and severity of polycythaemia. However, it did not correlate with partial oxygen
      pressure or arterial oxygen saturation. Uric acid excretion was measured in
      hyperuricaemia group. Urinary uric acid excretion (24 h) was within normal limits
      in infants but markedly lower in patients over 15 years of age. The aetiology of
      hyperuricaemia and decreased uric acid fractional excretion and clearance in
      infants appears to be secondary to diminished excretion of uric acid in concert
      with uric acid overproduction. Hyperuricaemia in adolescents and adults with
      CCHD, however, results mainly from age-related impairment of uric acid excretion.

PMID- 8276014
TI  - Aneurysmal dilatation of ductus arteriosus during lipo-prostaglandin E1 therapy
      for diaphragmatic hernia.
AB  - We report a case of congenital diaphragmatic hernia in which aneurysmal
      dilatation of ductus arteriosus developed after lipo-prostaglandin E1 (PGE1)
      therapy for persistent fetal circulation. After surgery Lipo-PGE1 was used at a
      dosage of 5 ng/kg per minute from days 2-9 during which aneurysmal dilatation (7
      mm in diameter) developed and remained thereafter. Ductus arteriosus ligation was
      then performed. Lipo-PGE1 may promote ductus arteriosus dilatation in cases of
      persistent fetal circulation.

PMID- 8276015
TI  - Gastro-oesophageal reflux in children: comparison of different durations,
      positions and sleep-awake periods of pH monitoring in the same patient.
AB  - A group of 72 children (mean age: 21.7 months, range: 14 days-19 years) with
      symptoms of gastro-oesophageal reflux were investigated by 22 h pH monitoring.
      Using a Proxeda software, we compared, in the same patient, the specificity and
      sensitivity of pH monitoring during 3 h, 6 h, 12 h, 12 nocturnal hours and 3
      postprandial hours, as well as the influence of position and the sleep and alert
      periods. Results showed that all the short pH monitorings were statistically less
      sensitive than 22 h pH monitoring (P < 0.025). As regards specificity, only the
      12 nocturnal hours pH monitoring was not statistically different from the 22 h pH
      monitoring. Gastro-oesophageal reflux was more frequent when the patient was
      awake than during sleep. pH monitoring seemed more reliable in the recumbent than
      in the upright position. We conclude that long-term pH monitoring (22 h) is the
      test of choice to diagnose gastro-oesophageal reflux because it included sleep
      and alert periods as well as different positions.

PMID- 8276016
TI  - Down syndrome and coeliac disease: five new cases with a review of the
      literature.
AB  - We report five new patients with coeliac disease and Down syndrome and review the
      11 cases previously reported in the literature. In 14 of these 16 patients
      diarrhoea was the presenting symptom and in 2 failure to thrive in combination
      with anaemia. The frequency of coeliac disease in children with Down syndrome was
      calculated as being 43 times greater than in children without Down syndrome.
      Delay between first symptoms and diagnosis in patients with combined coeliac
      disease and Down syndrome was 2.5 years, while in the other children with coeliac
      disease it was only 8 months. This distinctive difference could be caused by an
      underestimation of the seriousness of gastro-intestinal complaints in patients
      with Down syndrome. It is stressed that coeliac disease should be strongly
      considered in all children with Down syndrome and either persistent diarrhoea or
      failure to thrive.

PMID- 8276017
TI  - Growth following single fraction and fractionated total body irradiation for bone
      marrow transplantation.
AB  - Total body irradiation (TBI) is used as preparative regimen prior to bone marrow
      transplantation (BMT). Since there are more long-term survivors, follow up
      studies are important. We have performed a retrospective analysis of growth for
      49 children, who had undergone treatment with cyclophosphamide and TBI before
      BMT. Of these patients 26 received single fraction (SF) TBI as a dose of 900-1000
      cGy, whereas 23 received fractionated (FF) TBI as a total dose of either 1200 cGy
      divided in six fractions or 1440 cGy divided in eight fractions over 3 days. Half
      of the patients in the SF-TBI group, and 9 in the FF-TBI group had received low
      dose cranial irradiation prior to TBI. In all groups a decrease in height SDS was
      observed. By evaluating the major factors leading to growth impairment the
      influence of cranial irradiation, which was demonstrable in the 1st year after
      TBI, could not be shown after 3 years. At this time growth was significantly more
      impaired in the SF group with a mean height SDS of -0.9 (+/- SD 0.9) compared to
      a mean height SDS -0.22 (1.02) in the FF group (P < 0.05). Measurement of
      segmental proportions showed a significant difference in SDS for sitting height
      in comparison to SDS for subischial leg length, irrespective of the TBI regimen.
      This was already evident 1 year after TBI and decreased during the following
      years. Twenty four of the patients (17 in the single fraction and 7 in the
      fractionated TBI group) were treated with growth hormone, but demonstrated an
      inappropriate response with absent catch-up growth in their legs.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276018
TI  - The management of chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency disease which
      results from absence of the NADPH oxidase in the professional phagocytic cells
      neutrophils, monocytes, macrophages and eosinophils. Deficiency of this oxidase
      renders the patient liable to infection by bacteria and fungi, and, as the name
      of the disease suggests, to chronic granulomatous inflammation. These patients
      present with a great variety of infections and other complications of their
      disease, which often tax the clinical and therapeutic skill of the doctors
      responsible for their care. Collectively we look after, or advise on the
      management of, over 100 of these subjects, and have developed experience in the
      diagnosis and management of the infections and other clinical problems they
      present. We thought that it might be timely to provide guidelines for their
      management based upon this experience. The numbers of patients are still
      relatively small, and the clinical presentations very varied, so it is impossible
      to provide clear statistical proof of the veracity of this advice. It does,
      however, reflect the working practise of the physicians caring for many of these
      patients in Europe.

PMID- 8276019
TI  - X chromosome inactivation analysis to distinguish sporadic cases of X-linked
      agammaglobulinaemia from common variable immunodeficiency.
AB  - The X chromosome inactivation analysis of eight female relatives was performed to
      elucidate the X chromosome gene defect of six male hypogammaglobulinaemic
      individuals. The patients had diminished numbers of circulating B-cells and no
      relevant family history. The methylation status of three X-linked genes,
      phosphoglycerate kinase, hypoxanthine phosphoribosyl transferase and DXS255, was
      determined on DNA from Epstein-Barr virus-transformed B-cell lines established
      from the female relatives. The methylation pattern of at least one gene was
      informative in all eight females examined. While both alleles were equally
      methylated in four of eight females, the remaining four female relatives of three
      hypogammaglobulinaemia patients exhibited a non-random methylation pattern in
      their B-cells, suggesting that these three patients represented sporadic cases of
      X-linked agammaglobulinaemia (XLA). The clinical or immunological status of these
      three patients did not differ from the remaining two who had early onset
      hypogammaglobulinaemia and who were tentatively diagnosed as having common
      variable immunodeficiency. The sixth patient had recurrent infections after
      undergoing surgical removal of a brain tumour at 22 years of age, although his
      immunological features did not distinguish him from the other patients. X
      chromosome inactivation analysis can be useful in differentiating XLA from
      hypogammaglobulinaemia in male patients.

PMID- 8276020
TI  - Effects of laryngoscopy and tracheal intubation on cerebral and systemic
      haemodynamics in children under different protocols of anaesthesia.
AB  - The effects of laryngoscopy and tracheal intubation on cerebral and systemic
      haemodynamics were studied in 30 children. The objective was to identify
      conditions in which the alterations of cerebral and systemic haemodynamics were
      minimal. The children were intubated after muscular relaxation and following 10
      min of mechanical ventilation with end-tidal halothane concentrations of 1.5%,
      2.0% and 2.5%, respectively. With 1.5%, 2.0% and 2.5% end-tidal halothane, the
      mean flow velocity increased by 26%, 19% and 5%, the mean blood pressure by 14%,
      10% and 1%, and the heart rate by 26%, 8% and 5% respectively after intubation.
      Adverse effects of laryngoscopy and tracheal intubation on cerebral haemodynamics
      in children can be avoided by adequate anaesthetic protocols.

PMID- 8276021
TI  - Mutation analysis in the diagnosis of cystic fibrosis.
AB  - Since the characterization of the gene encoding the cystic fibrosis transmembrane
      conductance regulator protein and identification of its main mutation, delta
      F508, causing cystic fibrosis (CF), more than 150 mutations in this gene have
      been reported, most of them only in a few or even single CF patients. Attempts to
      use mutation analysis in genetic counselling or for the diagnosis of CF depends
      on prevalence data of certain mutations in the respective population, and
      considerable ethnic differences have been reported. In this study we determined
      the prevalence of the mutations delta F508, G551D, R553X, and G542X and of
      genotypes defined by these mutations in 239 CF patients (444 independent CF
      chromosomes) seen in our clinic. The analysis for those four mutations alone now
      permits identification of approximately 75% of all mutations in our CF patients.
      The complete genotype can be resolved in approximately 63% of patients. This
      represents the diagnostic sensitivity which can be achieved by mutation analysis
      in patients without a family history of CF. We conclude that in situations where
      conventional diagnostic tests are not feasible or difficult to interpret,
      mutation analysis using a limited set of mutations can contribute significantly
      to an early and specific diagnosis of CF.

PMID- 8276022
TI  - Calcium metabolism in the Jansen type of metaphyseal dysplasia.
AB  - The Jansen type of metaphyseal dysplasia (JMD) is a rare disorder characterized
      by growth disturbance and progressive metaphyseal changes initially reminiscent
      of rickets or primary hyperparathyroidism. Seven of the 16 patients described
      until now presented with hypercalcaemia of unknown origin. We report studies of
      calcium metabolism in a hypercalcaemic girl with JMD during the first 3 years of
      life. The patient presented with hypercalcaemia, hypercalciuria, elevated urinary
      phosphate and cyclic adenosine monophosphate (AMP) excretion as well as increased
      1,25-dihydroxyvitamin D concentrations in serum despite suppressed or low normal
      values of circulating intact parathyroid hormone (PTH) and PTH related peptide
      (PTHrP). Measurements of biochemical indices of bone turnover indicated increased
      bone resorption without sufficient compensatory bone formation. The study
      suggests that the hypercalcaemia in our patient was caused by an unknown factor,
      which is not PTH or PTHrP, with osteolytic activity and stimulatory effect on the
      proximal kidney tubule.

PMID- 8276023
TI  - Serpentine fibula--polycystic kidney syndrome and Melnick-Needles syndrome are
      different disorders.
AB  - We report on the third patient with serpentine fibula-polycystic kidney syndrome.
      Main features in the three reported cases were growth retardation, abnormal face,
      hirsutism, short neck, bowed forearms and lower legs due to bowed radii and
      elongated serpentine fibulae, and metatarsus adductus. Two patients including our
      own were deaf. All were mentally normal, all were female and sporadic. In
      addition, we report on a girl with Melnick-Needles syndrome and illustrate the
      similarities and differences between these syndromes.

PMID- 8276024
TI  - A new case of short-chain acyl-CoA dehydrogenase deficiency with isolated
      ethylmalonic aciduria.
AB  - A 28-month-old Turkish girl presented with recurrent bronchopneumonia and severe
      muscular hypotonia. Urinary excretion of ethylmalonic acid was persistently
      elevated, methylsuccinate appearing only in stress situations. Studies in
      cultured fibroblasts showed a deficiency of short-chain acyl-CoA dehydrogenase.

PMID- 8276025
TI  - Randomized trial comparing dopamine and dobutamine in preterm infants.
AB  - The aim of this study was to compare the efficacy of two inotropic infusions in
      treating low BP in preterm neonates. Forty infants with median gestational age 27
      weeks (range 23-33) were studied. At trial entry the infants, who all had a
      systolic BP < 40 mmHg despite receiving a colloid infusion, were randomized to
      receive either a dopamine or dobutamine infusion. The infusions were commenced at
      a rate of 5 micrograms/kg per min and, if necessary, this was increased over the
      3 h study period to 15 micrograms/kg per min. There was no significant difference
      in the gestational or postnatal age or baseline BP of the 20 infants who received
      dopamine and those 20 who received dobutamine. Three hours after commencing the
      infusions, although there was no difference in the rate of inotrope infusion
      between the two groups, the infants who received dopamine had a significantly
      higher systolic BP, a median of 39 mmHg (range 30-58) compared to a median of 34
      mmHg (range 21-46) in the dobutamine group, P < 0.05. In addition, 10 infants who
      received dopamine, but only 3 who received dobutamine, had a systolic BP > 40
      mmHg (P < 0.05). We conclude that dopamine rather than dobutamine infusion is
      more efficacious in improving the BP of preterm neonates.

PMID- 8276026
TI  - Endogenous fibrinolysis in neonatal cerebrospinal fluid.
AB  - Although many infants with intraventricular haemorrhage (IVH) recover without
      hydrocephalus, little is known about how blood is cleared from the CSF pathways.
      Fibrinolytic activity was measured by the fibrin plate method in CSF from 11
      normal infants and 17 infants with IVH. Normal CSF showed no fibrinolytic
      activity. All the samples taken less than 17 days from diagnosis of IVH failed to
      show fibrinolytic activity. All but 1 of the CSF samples taken between 17 and 60
      days of IVH showed fibrinolytic activity. In 1 infant where 14 serial samples
      were taken, there was no detectable fibrinolysis up to 16 days after IVH but from
      19 to 52 days there was definite fibrinolytic activity. Delayed endogenous
      fibrinolysis in the CSF is common after IVH but may, in some cases, be
      insufficient to prevent hydrocephalus.

PMID- 8276027
TI  - Ureaplasma urealyticum and chronic lung disease.
AB  - Neonatal lower respiratory tract colonisation with mycoplasma organisms was
      examined for an association with chronic lung disease. Ureaplasma urealyticum
      colonised 9/70 (13%) infants less than 1500 g. Seven (78%) colonised and 33 (54%)
      non-colonised infants developed chronic lung disease. Logistic regression
      analyses revealed early gestation, but not mycoplasma colonisation, was
      independently associated with chronic lung disease.

PMID- 8276028
TI  - Ranitidine-induced bradycardia in a neonate--a first report.
AB  - Bradycardia, an extremely rare side-effect of ranitidine therapy is described in
      a 4-day-old full-term male neonate, who was admitted because of massive gastro
      intestinal bleeding. Two hours after the intravenous injection of 1 mg/kg body
      weight per day, ECG showed sinus bradycardia of 60 beats/min with normal axis and
      QRS complex. The bradycardia gradually resolved in the next 24 h.

PMID- 8276029
TI  - Elevated beta-endorphin immunoreactivity in the cerebrospinal fluid in victims of
      sudden infant death correlates with hypoxanthine in vitreous humour.
AB  - Beta-endorphin (BEND) may induce respiratory depression. Elevated levels of beta
      endorphin immunoreactivity (BENDI) in the CSF are found in children with apnoea
      and in about 50% of sudden infant death (SID) victims. Premortal hypoxia in SID
      victims has been indicated by elevated hypoxanthine (HX) levels in the vitreous
      humour (VH). In this study we correlated BENDI in CSF with HX in VH in SID
      victims (n = 19) and controls (n = 18). BEND in CSF was measured by RIA, and HPLC
      was used for identification of BENDI. HX in VH was measured by HPLC. All the SID
      victims had elevated levels of HX in VH. The BENDI in CSF divided the SID victims
      into two subpopulations (P < 0.01); one with undetectable levels (< 4.3 fmol/ml)
      (n = 10) and one with high levels (160-400 fmol/ml) (n = 9). In the SID
      subpopulation with high levels of BENDI in CSF, we found a correlation between
      BENDI in CSF and HX in VH (r = 0.92). Control infants who died a stressful death,
      such as during heart operations (n = 2), had high levels of BENDI in CSF and low
      levels of HX in VH. Controls who died of infections (n = 11) had low levels of
      BENDI in CSF and elevated levels of HX in VH. Because hypoxia in itself does not
      increase BENDI in CSF, increased BENDI in CSF is probably not secondary to
      hypoxia but may be of aetiological significance.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276030
TI  - Follow up study on children with dyslipidaemia detected by mass screening at 18
      months of age: effect of 12 months dietary treatment.
AB  - The present study was done to evaluate the effect of short-term dietary therapy
      on 148 dyslipidaemic children (24 familial hypercholesterolaemia, 105 non
      familial hypercholesterolaemia and 19 hypertriglyceridaemia), detected by mass
      screening in children at 18 months of age. In the model diet used for treatment,
      15% of the total calories were obtained from protein, 27% from fat and 57% from
      carbohydrate. Cholesterol intake was set at < 200 mg/day and the ratio of
      polyunsaturated to saturated fatty acid (P/S ratio) was 1.2. When compared to the
      composition of the diet ingested by the dyslipidaemic children, only the P/S
      ratio changed from 0.7 to 1.2. During 12 months treatment, levels of total
      cholesterol, low density lipoproteins cholesterol and apoB decreased by 10%-15%
      in children with familial and non-familial hypercholesterolaemia. There was no
      significant change in the levels of high density lipoproteins. In 19 children
      with hypertriglyceridaemia, the intake of carbohydrate was limited to 55% of the
      total calories consumed and after 12 months of treatment, triglyceride levels
      reverted to normal. Throughout the study period, approximately 70% of the
      children on this dietary therapy were seen in our clinics every 3-6 months and
      physical development was within normal ranges. These results, taken together,
      indicate that dietary therapy can be effective for correcting dyslipidaemia, even
      in young children.

PMID- 8276031
TI  - Imidazoline intoxication in children.
AB  - A 15-month-old girl with rhinopharyngitis was treated with a nasal solution
      containing the imidazoline derivative naphazoline. She rapidly developed profound
      CNS depression with stupor, hypothermia, hypoventilation and bradycardia. All
      symptoms disappeared within 24 h. The symptomatology of 18 other paediatric cases
      of naphthylimidazoline exposure reported to the Belgian National Poison Centre,
      is also discussed. Imidazoline intoxication due to overdose or accidental
      ingestion but also after normal therapeutic usage is frequent in children. It can
      cause severe CNS depression, especially in very young children. For these reasons
      vasoconstrictor imidazoline containing solutions should be prescribed with
      caution and kept out of reach of children.

PMID- 8276032
TI  - Obturator internus muscle autotransplantation: a new concept for the treatment of
      obstructive constipation. An anatomical, physiological and pathological study.
AB  - The feasibility of using obturator internus muscle autotransplantation in order
      to construct an anal dilator mechanism for the treatment of obstructive
      constipation was studied anatomically, physiologically and pathologically.
      Electromyographic studies of 15 obturator internus muscles in 10 healthy adult
      male volunteers and 3 other muscles in patients with documented spastic anal
      sphincters demonstrated the ability of the obturator internus muscles to contract
      during straining at stools. The proposed surgical approach was studied in 9
      cadavers (5 stillbirths and 4 adults), followed by formal anatomical dissection
      of the obturator internus muscle and tendon, pudendal nerve and vessels, inferior
      rectal nerve and nerve to the obturator internus. Anatomical studies proved the
      feasibility, ease, rapidity and safety of the technique with or without division
      of the obturator internus tendon with no incidence of injury to the surrounding
      nerves, vessels or muscles using a purely perineal approach.

PMID- 8276033
TI  - Histological studies on postischemic rat skeletal muscles. With emphasis on the
      time of leukocyte invasion.
AB  - Several studies have suggested that the damage after ischemic injuries increases
      during reperfusion and that this reperfusion damage is mediated through
      granulocytes which invade the damaged area. The present study was undertaken to
      test these hypotheses by histological investigations of the anterior tibial
      muscles in a rat hind limb tourniquet model after 4.5 h of complete ischemia and
      graded periods of reperfusion. Uptake of albumin into damaged muscle fibers was
      demonstrated immunohistochemically and used to determine the extent of the
      ischemic lesions. The size of the lesions was measured morphometrically on
      immunostained sections from paraffin-embedded material. Granulocytes in and
      outside the capillaries were counted on slides from historesin-embedded material.
      Generally, there was a compact central area in the muscles which showed necrosis
      of all fibers and many capillaries, little interstitial edema, and little or no
      invasion of granulocytes or macrophages. The central core did not increase in
      size during the postoperative period. Outside this are there was a zone of
      partial tissue destruction with quite marked interstitial edema. This zone also
      remained unchanged in size but it is uncertain whether the number of necrotic
      fibers increased with time. There was an increasing invasion of granulocytes in
      this outer zone from 5 to 24 h after release of the occlusion and
      monocyte/macrophage invasion was seen from 48 h. Outside this zone there was a
      subfacial zone with normal muscle fibers in all cases. It is concluded that the
      central area of complete tissue destruction was present at the time of release of
      the occlusion and did not increase in size during the further postoperative
      course. There was no indication that granulocytes participated in this damage.
      The extent of the partially damaged area also remained unchanged during the
      postoperative course. It is conceivable that granulocytes aggravated the lesions
      by increasing the number of necrotic fibers in this peripheral area but not
      before 5 h after release of the occlusion. This is later than described in
      previous studies.

PMID- 8276034
TI  - Effect of platelet on protein degradation in rat skeletal muscle.
AB  - The effects of activated platelet (Plt) on muscle degradation were investigated,
      employing the in vivo disseminated intravascular coagulation (DIC) model induced
      by thrombin injection and the in vitro tissue culture system of skeletal muscles
      in rats. Both the release of tyrosine and leucine into the culture medium during
      2 h incubation from the muscles harvested 30 min after thrombin injection
      increased by about 50% compared with control muscles. The addition of thrombin
      activated platelet supernatant (TAPS) significantly increased the release of
      leucine into the incubation medium of the soleus muscles dissected from normally
      fed rats by 31% in comparison with the respective controls. No significant effect
      was observed in terms of the release of tyrosine or leucine from the incubated
      muscles by aspirin treatment before obtaining TAPS, or by the addition of
      thrombin itself up to the concentration of 0.67 micron/ml which was contained in
      the incubation medium of TAPS. These data suggest that protein catabolism is
      accelerated in the muscle from the thrombin-treated rats exhibiting DIC. The
      supernatant of activated Plt might contain a factor which modulates protein
      metabolism. That factor is different from prostaglandins or thrombin. Thus,
      active consumption of Plt may contribute to an increase of muscle breakdown in
      various catabolic states.

PMID- 8276035
TI  - Fecal peritonitis--the effect on anastomotic healing.
AB  - The present study evaluates colonic anastomosis healing in the presence of fecal
      peritonitis in rats. After induction of fecal peritonitis, the animals were
      treated by surgery alone or with the addition of systemic supportive treatment.
      It is shown that survival in the latter group was significantly better, while
      burst strength of anastomoses in surviving animals in both groups was identical.
      The results suggest that the outcome of fecal peritonitis depends mainly on fluid
      resuscitation and antimicrobial therapy, but not on primary repair.

PMID- 8276036
TI  - Skin prolylhydroxylase activity and wound healing.
AB  - The relationship between wound healing and skin prolylhydroxylase activity was
      examined in 212 patients undergoing reconstructive procedures and 109 controls
      using skin prolylhydroxylase activity as an index of collagen synthesis. In the
      control group, the median value of skin prolylhydroxylase activity was 360 cpm/mg
      protein. There was a higher skin prolylhydroxylase activity in 274 patients with
      successful healing (368 cpm/mg protein) than there was in 33 patients who
      required local wound care (202 cpm/mg protein) and 14 patients with severe local
      complications (71 cpm/mg protein, p = 0.02). Skin prolylhydroxylase activity was
      also significantly lower (p = 0.002) in patients with laboratory criteria for
      malnutrition (albumin < 3.5 g/dl, 108 cpm/mg protein; total lymphocyte count <
      1,500 mm3, 211 cpm/mg protein, and albumin < 3.5 g/dl + lymphocyte count < 1,500
      mm3, 52 cpm/mg protein), but age, diabetes mellitus, malignancy and wound
      infection did not affect skin prolylhydroxylase activity. These results suggest
      that skin prolylhydroxylase activity is reduced in patients with malnutrition and
      delayed wound healing.

PMID- 8276037
TI  - The rat gastric phospholipids: increased in ulcerated mucosa and decreased after
      healing.
AB  - The composition and content of the gastric phospholipids were followed during
      development and healing of indomethacin-induced chronic, antral ulcers in rats.
      The individual phospholipids were identified by thin-layer chromatography and
      quantitatively estimated by spectrophotometric analysis of phosphate. No changes
      were found in phospholipid composition and content after a 24-hour fast or during
      the first 24 h after indomethacin was given. The total phospholipid content and
      the content of lysophosphatidylcholine and phosphatidylcholine were increased on
      the 5th day, when chronic ulcers were established. After 4 weeks, when the ulcers
      were healed, the total phospholipid content, and content of phosphatidylcholine,
      phosphatidylethanolamine and phosphatidylinositol, respectively, were decreased,
      while the content of lysophosphatidylcholine was increased. In conclusion, the
      composition and content of gastric phospholipids were altered in rats with ulcers
      as well as in rats with healed ulcers.

PMID- 8276038
TI  - Differences in the vascular response to terbutaline in the native and
      transplanted rat pancreas.
AB  - Syngeneic pancreaticoduodenal transplantations were performed in Wistar-Furth
      rats. Fourteen days after implantation, blood perfusion of the whole native and
      transplanted pancreas, the pancreatic islets and the native and transplanted
      duodenum was measured with a microsphere technique 5 min after an intravenous
      injection of 0.5 ml of either saline (n = 6) or terbutaline (1 mg/kg BW; n = 9).
      Terbutaline decreased the mean arterial blood pressure by approximately 30% (p <
      0.001). The substance also decreased the whole pancreatic blood flow of the
      native pancreas (p < 0.05), but not of the transplanted gland. However, the
      vascular conductance of the whole pancreas was unchanged after terbutaline
      administration in both the native and transplanted gland. Islet blood flow (p <
      0.001) and islet vascular conductance (p < 0.01) were markedly decreased in the
      native pancreas. In the transplanted gland, there was, however, no change in
      islet vascular conductance and only a slight decrease in islet blood flow (p <
      0.05). Both the native and transplanted duodenal blood flows were unaffected by
      terbutaline. One likely explanation for the different effects of terbutaline on
      the blood perfusion of the native and transplanted pancreas may be that the
      latter gland is devoid of any physiologically relevant exogenous innervation.

PMID- 8276039
TI  - Improved technique of 70% hepatectomy in dogs.
AB  - An improved anatomical technique for extended hepatectomy in dogs is described as
      a model to study the process of liver regeneration. The crucial steps in the
      technique as well as the site of bile duct ligation and dissection of the left
      hepatic vein are described in detail. Using this method extended hepatectomy was
      done without any mortality or morbidity in more than 20 dogs.

PMID- 8276040
TI  - Anorectal tightening reflex: role in fecal incontinence.
AB  - The present study describes the clinical significance of the anorectal tightening
      reflex (ATR) in normal and incontinent subjects. It was examined in 16 healthy
      volunteers and 11 subjects incontinent to flatus and fluid stools; 5 of the
      latter had in addition fecal soiling. The rectum was distended by a condom
      inflated with carbon dioxide, while the rectal and rectal neck (RN) (anal canal)
      pressures were measured, and the external (EAS) and internal anal sphincter (IAS)
      EMG activity was recorded. The rectum was inflated at two rates: slow and rapid.
      In normal subjects, the RN pressure increased upon slow rectal inflation; the IAS
      EMG was augmented. Pudendal nerve block and phentolamine administration revealed
      that this pressure increase is due to increased IAS tone which tightens the RN
      against the slow rectal filling by the time adaptive reaction occurs. Rapid
      rectal filling evoked Gower's rectoinhibitory reflex. Thus, while increased IAS
      tone in the ATR protects against involuntary incontinence upon 'slow' rectal
      filling, the increased EAS tone of Gower's reflex protects in the case of 'rapid'
      filling. Of the 11 incontinent patients, the 5 with fecal soiling did not show
      ATR, and investigative results pointed to the IAS as being responsible for
      incontinence. The other 6 patients had normal ATR but nonresponsive EAS on rapid
      filling. Findings suggest that the ATR plays a role in maintaining continence
      during slow rectal distension and that a disordered ATR due to IAS dysfunction
      leads to fecal incontinence. Thus ATR may be useful as an investigative tool in
      anorectal disorders.

PMID- 8276041
TI  - Drug related hospital admissions. Results from an intervention program.
AB  - As part of a high-intensity monitoring study of drug events as the cause of
      admission to departments of internal medicine, the effect of an educational
      intervention programme was studied. Two departments were included, one
      specialising in geriatrics and one that received patients by non-selected
      referral. The series consisted of 607 consecutive admissions studied before and
      703 after the intervention. The drug events considered were adverse drug
      reactions and dose-related therapeutic failures, mainly due to non-compliance. A
      modest, statistically non-significant decrease in drug related hospital
      admissions (DRH) was seen, from 14% before to 13% after the intervention period.
      However, DRHs classified as definitely avoidable showed the significant decrease
      of 83%. There was no apparent relationship between the topics selected for the
      intervention programme and changes in the pattern of DRHs. No relationship
      between alterations in sales data and hospital admissions caused by a given drug
      could be demonstrated. A blinded external evaluation of case abstracts did not
      disclose any significant shift in the investigators' assessments. The
      intervention may have had an non-specific effect on avoidable DRHs.

PMID- 8276042
TI  - The use of antidepressant drugs in general practice. A questionnaire survey.
AB  - The aim of this study was to examine the anti-depressant drug prescribing
      preferences and habits of a population of general practitioners. The method used
      was that of a questionnaire survey, including case vignettes. The response rate
      exceeded 70% Data are presented out-lining the attitudes of the respondents to
      the use of antidepressant drugs in the management of common psychiatric
      presentations in the primary care setting. The majority of general practitioners
      (G.P.'s) had received little or no post-graduate education in psychiatry. The
      antidepressants most frequently prescribed were amitriptyline, clomipramine,
      trazodone and lofepramine. Despite recognition of the alarming frequency of
      serious self-poisoning incidents with some of these compounds, 26% of respondents
      confessed to an inability to make an informed choice of antidepressant drug, with
      14% using the same drug with every patient with no attempt to select according to
      individual patient requirements. The management of depressive neurosis generates
      considerable clinical confusion with a variety of interventions favoured. The use
      of a sedating antidepressant is popular. There is greater accord for the
      management of endogenomorphic depression. The use of the benzodiazepine drugs in
      the management of anxiety disorders is infrequent, with appropriate recognition
      of the merits of behavioural approaches. However, the role for antidepressant
      drugs in the management of anxiety disorders is under-recognized. We conclude
      that general practitioners are required to undertake a significant body of work
      for which they may be inadequately trained.

PMID- 8276043
TI  - Actual versus prescribed timing of lovastatin doses assessed by electronic
      compliance monitoring.
AB  - The objective of the study was to compare compliance with and the
      hypocholesterolaemic effect of lovastatin given once daily as a morning or an
      evening dose. Twenty-four out-patients with familial hypercholesterolaemia were
      randomly assigned to receive placebo first, then lovastatin 20 mg, to be taken
      once daily for 4 weeks, either with the breakfast or evening meal, in a single
      blind fashion. Drug compliance was assessed by pill counts and continuous
      electronic monitoring. Two compliance parameters were evaluated, consumption,
      defined as percentage of prescribed doses taken, and time compliance, the
      percentage of total dosing events recorded within defined intervals (6.00-10.00
      h, and 17.00-21.00 h), for the morning and evening regimes. Both regimes
      satisfactorily reduced the total and LDL-cholesterol concentrations, and there
      was no significant difference in the extent of the reductions. Pill counts
      overestimated compliance, as revealed by the monitoring method. The times of
      actual consumption of doses by the patients often differed from that prescribed,
      predominantly in patients who were told to take the evening dose. Partial time
      compliance may have confounded the efficacy of the drugs. Electronic compliance
      monitoring appears to be particularly useful in chronopharmacological studies.

PMID- 8276044
TI  - The effect of prostaglandin E1 during cardiopulmonary bypass on renal function
      after cardiac surgery.
AB  - We have evaluated the effect of prostaglandin E1 (PGE1) on renal function after
      cardiac surgery with cardiopulmonary bypass in 20 patients, ten of whom received
      0.02 microgram.kg-1.min-1 of PGE1 by infusion into the oxygenator during bypass;
      ten patients served as controls. Serum beta 2-microglobulin fell significantly
      and urine beta 2-microglobulin increased significantly after surgery in both
      groups. Urine N-acetyl-beta-D-glucosaminidase was high after surgery in both
      groups, but it was significantly lower in the PGE1 group. Free water clearance
      fell significantly on the 1st, 3rd, and 5th postoperative days compared with
      preoperative values in the control but not in the PGE1 group. These results
      suggest that PGE1 may prevent renal dysfunction after cardiopulmonary bypass.

PMID- 8276045
TI  - Cholic acid and ursodeoxycholic acid therapy in primary biliary cirrhosis.
      Changes in bile acid patterns and their correlation with liver function.
AB  - We treated 6 patients with Stage II primary biliary cirrhosis with cholic acid
      (CA) 10 mg.kg-1 per day for 3 months and then with the same dose of
      ursodeoxycholic acid (UDCA). A matching group of 6 patients was observed for 3
      months without any therapy. Liver function tests and serum and stool bile acids
      were investigated before, during and at the end of CA and UDCA therapy. The
      results of liver function tests deteriorated after 6-8 weeks of CA therapy and
      the changes were correlated (r = 0.92) with an increase in alpha-dihydroxy-bile
      acids (chenodeoxycholic acid and deoxycholic acid) in the serum. The 24 h
      excretion of DCA in 24 h faeces was markedly increased. Ursodeoxycholic acid
      treatment improved liver function tests; after 4 weeks glutamate dehydrogenase
      (GLDH) had decreased. After 8-12 weeks of therapy ursodeoxycholic acid had
      increased to 50-60% of the total serum bile acids whereas the more apolar bile
      acids were significantly decreased. No changes in liver function tests or bile
      acid metabolism were found in the untreated group. Since CA and UDCA are non
      toxic in man, this trial indicates that the apolar bile acids chenodeoxycholic
      acid and deoxycholic acid may be responsible for the deterioration of liver
      function in primary biliary cirrhosis. However, the therapeutic effect of UDCA
      cannot be explained merely by the decrease in alpha-dihydroxy-bile acids in the
      serum, since the laboratory results had improved prior to the decrease in the
      serum apolar bile acids.

PMID- 8276046
TI  - Trials of the bronchodilator activity of the xanthine analogue SDZ MKS 492 in
      healthy volunteers during a methacholine challenge test.
AB  - An approximately steady-state reduction of specific airway conductance was
      induced in healthy human subjects by means of an individualized inhaled
      methacholine loading dose followed by a maintenance dose regime. Tested against
      this background bronchoconstriction, the xanthine analogue SDZ MKS 492, when
      administered as a single oral dose of 40 mg, showed a significant bronchodilator
      action, which lasted for up to 5.5 h. Bronchodilatation was not seen after
      administration of 10 or 20 mg doses. SDZ MKS 492 inhaled as a dry powder had a
      bronchodilator action that was small, most evident with the 12 mg dose and
      transient. The peak relief of imposed bronchoconstriction was 29% and the
      apparent half-time of removal of SDZ MKS 492 from its site of action was 5-6 min.
      Inhaled SDZ 492 had a bitter taste that was not masked by inclusion of menthol
      and aspartame in the formulation. The bronchodilatation seen in laboratory
      animals can also be produced by SDZ MKS 492 in man when administered orally or by
      inhalation. Its magnitude correlates better with the plasma concentration of
      parent drug than with that of either of the identified metabolites. Dispositional
      processes in the lung abbreviate its action after administration by inhalation.

PMID- 8276047
TI  - Amnesic effects and subjective ratings during repeated dosing of flunitrazepam to
      healthy volunteers.
AB  - Flunitrazepam (1 mg) or placebo was administered once daily over a treatment
      period of 8 days to healthy, male volunteers to study the time course of the
      effects on memory functions and on subjective ratings of alertness and tension.
      The plasma level of flunitrazepam increased by approximately 40% (P < 0.05)
      during the treatment period. The mean pre-dose level of flunitrazepam on day 4
      and day 8 was approximately 0.005 microM, and no residual effects on memory
      functions were observed. Intake of flunitrazepam decreased the number of freely
      recalled words by about 85% (P < 0.05) and significantly affected the subjects'
      rating of attention when tested during the first few hours after drug intake on
      day 1 of treatment. However, no significant effect on the subjects' rating of
      relaxation was observed. When tested similarly after 8 days treatment,
      flunitrazepam significantly affected the subjects' rating of relaxation (P <
      0.01). Furthermore, no tolerance developed for the effect of flunitrazepam on
      free recall (P > 0.3) and the subjects' rating of attention (P > 0.7), and these
      effects had nearly equal time courses during the treatment period. This may
      indicate that the amnesic effect of benzodiazepines is at least partially
      mediated through the effects on attention or general arousal. Two of the subjects
      in the active drug group reported adverse reactions or incidents of discomfort
      during the 1st week following the treatment period, whereas none in the placebo
      group reported such reactions.

PMID- 8276048
TI  - Acute haemodynamic effects and pharmacokinetics of ramipril in patients with
      heart failure. A placebo controlled three-dose study.
AB  - The aim of the present study was primarily to evaluate the haemodynamic effects
      of the ACE-inhibitor ramipril which is active via its metabolite ramiprilat.
      Ramipril 1.25, 2.5 and 5 mg and placebo was administered orally to 4 groups of 12
      patients with heart failure (NYHA III) in a double-blind randomised, parallel
      study. Haemodynamics were monitored for 24 h and blood was sampled and urine
      collected for up to 96 h. In the placebo-treated group the cardiac index (CI) was
      significantly increased (15.8%) and right atrial pressure decreased (26.6%).
      Ramipril 1.25 mg had insignificant haemodynamic effects compared to placebo and
      the 2.5 mg dose had significant effects on some haemodynamic variables. Ramipril
      5 mg had pronounced and sustained effects on pulmonary artery pressure, which
      fell by 43.7%, and pulmonary capillary wedge pressure (PCWP; -59.1%); systemic
      vascular resistance was also decreased 21%. A significant effect on CI was only
      seen after 2.5 mg ramipril (+7.4%). The mean maximal degree of ACE inhibition was
      73.2, 90.4 and 98.5%, respectively, after the three doses of ramipril. Complete
      inhibition of ACE-activity was seen at a mean plasma concentration of ramiprilat
      of 4.7 ng.ml-1. The degree of inhibition declined with a half life of about 75 h.
      There was a significant relation between the degree of ACE-inhibition and change
      in PCWP but not with the change in SVR. Ramipril was mainly eliminated in the
      form of ramiprilat and inactive metabolites.

PMID- 8276049
TI  - Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE
      inhibitor spirapril in patients with chronic liver disease.
AB  - The pharmacokinetics and haemodynamic effects of orally administered spirapril, a
      novel angiotensin-converting enzyme (ACE) inhibitor, have been investigated in
      patients with liver cirrhosis (n = 10), in patients with chronic, non-cirrhotic
      liver disease (n = 8) and in a control group of healthy subjects (n = 16). The
      absorption and elimination of spirapril did not differ between patients with
      liver disease and control subjects. In contrast, the bioavailability of
      spiraprilat, the metabolite responsible for the pharmacological action of
      spirapril, was significantly reduced in patients (AUC 820 micrograms.h.l-1, 923
      micrograms.h.l-1 and 1300 micrograms.h.l-1 in patients with cirrhosis, patients
      with non-cirrhotic liver disease and in healthy subjects, respectively. Compared
      to healthy subjects, cirrhotic patients had a reduced rate constant of
      spiraprilat formation (1.10 h-1 in patients vs. 2.00 h-1 in control subjects)
      while the elimination half-life of spiraprilat was not different. The effect of
      spirapril on diastolic blood pressure was decreased in patients with chronic
      liver disease as compared to the controls. Thus, the pharmacokinetics of
      spirapril was unchanged in patients with different types of liver disease,
      including cirrhosis. However, the bioavailability of spiraprilat and hypotensive
      effect of spirapril were reduced in patients.

PMID- 8276050
TI  - The pharmacokinetic and pharmacodynamic interactions of ramipril with
      propranolol.
AB  - We have studied the pharmacodynamic effects of ramipril, propranolol, and their
      combination, as well as the effect of propranolol on the pharmacokinetics of
      ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and
      placebo, ramipril and placebo, or propranolol and ramipril were given orally for
      four days in a crossover, double-blind fashion. The pharmacokinetics of ramipril
      and ramiprilat were investigated on day 4. Effects on plasma renin activity, ACE
      activity, and heart rate and blood pressure both before and after a standardized
      exercise test were measured on days 1 and 4. On day 4 the combination reduced the
      mean arterial pressure by 2.8 mmHg compared with propranolol alone and by 3.7
      mmHg compared with ramipril alone. Ramipril had no effect on the bradycardia
      induced by propranolol. Propranolol reduced exercise mean arterial pressure by 9
      mmHg (day 4) and heart rate by 7 beats.min-1 (day 4) compared with ramipril; this
      was not affected by co-administration of ramipril. On day 4 the average plasma
      renin activity was not significantly higher than after the combination. ACE
      activity was not affected by propranolol. The pharmacokinetics of ramipril and
      ramiprilat were not influenced by propranolol. The combination of ramipril and
      propranolol has additive pharmacodynamic effects that may be useful in the
      treatment of hypertension.

PMID- 8276051
TI  - Interactions of bupranolol with the polymorphic debrisoquine/sparteine
      monooxygenase (CYP2D6).
AB  - The beta-adrenoceptor blocker bupranolol turned out to be a competitive inhibitor
      of the polymorphic cytochrome P450 CYP2D6 of which sparteine is a substrate.
      There was stereo-selectivity of bupranolol involved: (-)-bupranolol was the
      weakest inhibitor with an apparent Ki value of 1.32 microM, (+)-bupranolol was
      the most potent with an apparent Ki value of 0.55 microM, while the
      therapeutically used racemic bupranolol had an intermediate value of 0.88 microM.
      A 10 min pre-incubation of 5 microM bupranolol with the enzyme preparation prior
      to the addition of substrate, reduced the inhibition of sparteine metabolism from
      52 to about 25%. This suggests that--during these inhibition studies--bupranolol
      was much more rapidly metabolized than was sparteine, so that the measured Ki
      values must represent overestimates. The enzyme catalysing bupranolol metabolism
      was CYP2D6: microsomes from a liver with the genetic enzyme deficiency did not
      metabolize bupranolol; in microsomes from livers containing the enzyme and 10
      microM bupranolol, 5 microM quinidine caused a 72% inhibition of bupranolol
      metabolism. Although our methods were not sufficiently sensitive to measure the
      Km of bupranolol directly, it is undoubtedly the beta-adrenoceptor blocker with
      the highest-known apparent affinity for CYP2D6. High affinity and rapid
      metabolism are infrequent combinations in enzymology.

PMID- 8276052
TI  - Role of cytochrome P4502D6 in the metabolism of brofaromine. A new selective MAO
      A inhibitor.
AB  - The metabolic fate of brofaromine (CGP 11 305 A), a new, reversible, selective
      MAO-A inhibitor, has been assessed in poor (PM) and extensive (EM) metabolizers
      of debrisoquine. Compared to EM, PM had significantly longer t1/2 (136%) and
      larger AUC(0-infinity) (110%) of the parent compound brofaromine and a lower Cmax
      (69%) and AUC (0-72 h) (40%) of its O-desmethyl metabolite. The mean
      metabolite/substrate ratio (based on urine excretion) was about 6-times greater
      in EM than in PM. Treatment with quinidine converted all EM into phenocopies of
      PM. All pharmacokinetic parameters of brofaromine and O-desmethyl-brofaromine in
      EM treated with quinidine were similar to those of untreated PM, including the
      metabolite/substrate ratio. Quinidine treatment of PM did not alter the
      pharmacokinetics of brofaromine or of its metabolite, nor the
      metabolite/substrate ratio. The results indicate a role for the debrisoquine type
      of oxidation polymorphism in the O-demethylation and pharmacokinetics of
      brofaromine.

PMID- 8276053
TI  - Dextromethorphan O-demethylation polymorphism in Jordanians.
AB  - The O-demethylation of dextromethorphan (DMT) to dextrorphan (DRP) was studied in
      241 unrelated, healthy Jordanian volunteers (171 males, 70 females). Urine was
      collected for 8 h following a single oral dose of DMT bromhydrate 30 mg. A thin
      layer chromatographic (TLC) technique was used to identify the metaboliser
      phenotype. The frequency of the poor metaboliser phenotype was found to be 2.9%
      (approximate 95% confidence interval 0.8-5.0%). Applying the Hardy-Weinberg Law,
      the frequency of the recessive autosomal gene controlling poor metabolism was
      0.17 (95% confidence interval 0.108-0.232).

PMID- 8276054
TI  - Pharmacokinetics of fenoterol in pregnant and nonpregnant women.
AB  - The pharmacokinetics of the beta 2-adrenergic drug fenoterol, which is used as a
      tocolytic agent in pregnancy, has been investigated in pregnant (n = 9) and
      nonpregnant (n = 5) women during a constant rate intravenous infusion. Clearance
      and mean residence time were found to be 1990 (1879/2220; Median, Q25/Q75) ml/min
      and 9.2 (8.0/14.0) min in the pregnant and 2126 (1915/2130) ml/min and 16.6
      (16.5/32.1) min in the nonpregnant women, respectively. In addition, fenoterol
      clearance was estimated in 88 women from a single blood sample collected at
      steady state during IV therapy and the effect of gestational age on clearance was
      studied. Clearance displayed large interindividual variation. There was no
      apparent correlation between clearance and gestational age. We conclude that
      there is no need to adjust the dose on pharmacokinetic grounds in the course of
      pregnancy.

PMID- 8276055
TI  - Acetylator polymorphism in rheumatoid arthritis.
AB  - Acetylator phenotype has been determined with sulphamethazine (sulphadimidine) in
      69 Spanish patients with rheumatoid arthritis (48 females), all of whom were on
      second line therapy, and in 96 age-matched normal controls (54 females). Thirty
      two patients (46.4%) and 56 controls (58.3%) were classified as slow acetylators.
      On analysing separately the females in both groups, 37.5% of patients and 63% of
      controls were found to be slow acetylators. No difference was found in the males
      (patients 66.3% and controls 52.4% slow acetylators). Rapid acetylator phenotype
      may be a risk factor for the development of severe rheumatoid arthritis in women.

PMID- 8276056
TI  - Changes in plasma and urinary 11-dehydrothromboxane B2 in healthy subjects
      produced by oral CS-518, a novel thromboxane synthase inhibitor.
AB  - When 50 mg CS-518, a novel thromboxane (TX) A2 synthase inhibitor, was orally
      administered to healthy male volunteers, the plasma concentration of CS-518
      peaked after 0.5 h and then decreased with a half-life of 0.44 h. There was no
      significant change in the plasma concentration of circulating TXB2, whereas that
      of circulating 11-dehydrothromboxane B2 (11-dhTXB2), an enzymatic metabolite of
      TXB2, was significantly decreased from 0.5 h to 24 h after administration; the
      maximal decrease to about 25% of the pre-dose value was found at 6 h. After CS
      518 100 mg b.d. for 4.5 days, plasma 11-dhTXB2 was suppressed to the same extent
      as after the single dose of 50 mg from 6 h after the initial dose throughout the
      administration period. The urinary excretion of 11-dhTXB2 corrected for the
      creatinine level was significantly decreased by 70-84% throughout the treatment.
      These results suggest that CS-518 causes long-lasting inhibition of TXA2 synthase
      despite its rapid elimination from plasma, and that circulating 11-dhTXB2 in
      plasma and its urinary excretion can serve as a quantitative index of TXA2
      synthase inhibition in vivo by CS-518.

PMID- 8276057
TI  - Time course of the changes in prednisolone pharmacokinetics after co
      administration or discontinuation of rifampin.
AB  - We have investigated changes in the pharmacokinetics of prednisolone caused by co
      administration or discontinuation of rifampin. Serial IV pharmacokinetic studies
      of prednisolone (1 mg/kg) in groups of 3 patients over a 1 month period of
      rifampin co-treatment or after its withdrawal, revealed significant changes in
      the area under the curve, the total clearance, the non-renal clearance and the
      half-life. The changes in the pharmacokinetic parameters reached a 1.5 to 2-fold
      plateau after 2 weeks and the half maximal effect was attained within 5 days.
      Neither the volume of distribution nor the protein binding of prednisolone were
      significantly altered.

PMID- 8276058
TI  - Moexipril does not alter the pharmacokinetics or pharmacodynamics of warfarin.
AB  - The potential effect of moexipril, a new converting enzyme inhibitor, on the
      pharmacokinetics and pharmacodynamics of a single dose of warfarin has been
      investigated. Ten healthy male volunteers received in a randomised crossover
      fashion a single oral dose of 50 mg warfarin sodium alone and together with the
      first dose of 6 days of oral treatment with moexipril 15 mg o.d. Mean oral plasma
      clearance of (R)-warfarin was 175 ml.h-1 in the absence and 181 ml.h-1 in the
      presence of moexipril, and the corresponding values for (S)-warfarin were 248
      ml.h-1 and 249 ml.h-1. Apparent volume of distribution, peak plasma
      concentration, time to reach peak concentration and area under the plasma
      concentration-time curve both of (R)- and (S)-warfarin were not significantly
      affected. Moexipril did not alter the maximum prothrombin time (20.3 versus 20.1
      s, respectively in the absence and presence of moexipril), time to maximum
      response (48.0 versus 50 h) and area under the prothrombin time versus time
      curve. The results suggest that a clinically important interaction between
      moexipril and warfarin is unlikely to occur in patients treated with both drugs.

PMID- 8276059
TI  - Effect of ICI197067, a kappa-opioid receptor agonist, spinally on A delta and C
      reflexes and intracerebrally on respiration.
AB  - Intrathecal (i.t.) injection of a kappa-opioid receptor agonist, ICI197067,
      caused a similar dose dependent depression of A delta and C fibre mediated
      nociceptive reflexes in renal sympathetic nerves due to supramaximal electrical
      stimulation of tibial nerves in anaesthetized dogs. A total dose of 8 mg i.t.
      abolished these reflexes. When administered into the 4th ventricle (i.c.v.) in a
      total dose range from 0.1-2.5 mg ICI197067 caused no respiratory depression; a
      total dose of 10 mg i.c.v. abolished both phrenic nerve activity and spontaneous
      respiration. The ED50 ratio of ICI197067 for depression of respiration (i.c.v.)
      and somatosympathetic reflexes (i.t.) is approximately 1.5:1 compared with 0.3:1
      for fentanyl. ICI197067 i.c.v. caused a similar reduction in arterial pressure
      compare to fentanyl without comparable changes in heart rate. Thus in terms of
      cardiorespiratory depression and blockade of A delta and C fibre pathways kappa
      opioid receptor agonists may be safer and more effective for producing spinal
      analgesia than mu-opioid receptor agonists.

PMID- 8276060
TI  - Inhibition of cocaine-induced sensitization by the delta-opioid receptor
      antagonist naltrindole.
AB  - The influence of the delta-opioid receptor antagonist naltrindole upon
      sensitization to the locomotor activating effects of cocaine was assessed.
      Activity in response to a challenge dose of cocaine (20 mg/kg, i.p.) was
      significantly increased in rats which had received cocaine (20 mg/kg, i.p.) once
      daily for 3 days as compared to those which had previously received saline. The
      repeated administration of naltrindole (0.3-3.0 mg/kg, s.c.) alone did not affect
      activity. However, in animals which had received both naltrindole and cocaine for
      3 days, no sensitization to the locomotor activating effects of cocaine was
      observed. These data demonstrate that the selective blockade of delta-opioid
      receptors modifies the development of cocaine-induced sensitization and suggest
      an important role of delta-opioid receptor systems in modulating the development
      of drug-induced sensitization.

PMID- 8276061
TI  - Analgesic potency of S-acetylthiorphan after intravenous administration to mice.
AB  - As hydrolysis in serum of acetorphan to acetylthiorphan (N-[(R,S)-3
      acetylmercapto-2-benzylpropanoyl]glycine) has been evidenced, both the neutral
      endopeptidase inhibition in vitro by acetylthiorphan and analgesic potency of
      acetylthiorphan after intravenous administration to mice in two analgesic models,
      the hot-plate and the tail-flick tests, were compared with those of thiorphan and
      acetorphan. Acetylthiorphan showed a decreased degree of neutral endopeptidase
      inhibition (IC50 = 316 +/- 38 nM) compared to thiorphan (IC50 = 1.8 +/- 0.2 nM).
      After intravenous administration followed by the hot-plate jump latency test,
      acetylthiorphan elicited a degree of analgesia equivalent to that with acetorphan
      but longer lasting. Like acetorphan and thiorphan, acetylthiorphan was devoid of
      analgesic activity in the tail-flick test. The results indicated that S
      acetylation of the thiol function in acetylthiorphan ensures sufficient
      lipophilicity to permit crossing of the blood-brain barrier and that
      acetylthiorphan acts via a prodrug mechanism.

PMID- 8276062
TI  - Doridosine derivatives: binding at adenosine receptors and in vivo effects.
AB  - Doridosine, an adenosine analogue, causes, in vivo, hypotension, reduction of
      heart rates, muscle relaxation and anti-inflammatory effects through adenosine A1
      and A2 receptors. A series of doridosine derivatives was synthesized in a search
      for compounds with more selective adenosine A1 receptor activity. These
      derivatives were characterized for binding to the respective adenosine receptors
      and for their cardiovascular effects. We used competition binding studies with
      highly selective radioligands: [3H]cyclohexyladenosine for adenosine A1 and
      [3H]CGS 21680 for adenosine A2 binding assays. The results for eight doridosine
      derivatives revealed that 1-cyclopropylisoguanosine (BN-063) and 1
      allylisoguanosine (AZ-108-1) were more selective for the adenosine A1 receptor.
      In vivo, both BN-063 and AZ-108-1 caused significant bradycardia but no obvious
      effect on blood pressure. The bradycardia was almost completely blocked by 1,3
      dipropyl-8-cyclopentylxanthine (DPCPX, a specific adenosine A1 receptor
      antagonist).

PMID- 8276063
TI  - Reversal of nitroglycerin tolerance in vitro by the cGMP-phosphodiesterase
      inhibitor zaprinast.
AB  - Following in vitro exposure of rat aortic rings to 550 microM nitroglycerin for 1
      h, tolerance was demonstrated by a significant increase in EC50 values for
      nitroglycerin-induced relaxation. However, cross-tolerance to sodium
      nitroprusside was not observed. Co-incubation of aortic rings with the cGMP
      phosphodiesterase (cGMP-PDE) inhibitor zaprinast (10 microM), during incubation
      with 550 microM nitroglycerin, did not prevent the development of tolerance.
      However, the addition of 0.30 or 10 microM zaprinast to tolerant aortic rings did
      restore responsiveness to nitroglycerin. The increase in cGMP in tolerant aortic
      rings in response to 300 nM nitroglycerin (2-4 fmol/micrograms) was significantly
      less than that observed for non-tolerant rings (6.6-12 fmol/micrograms), but cGMP
      levels were restored in tolerant rings by zaprinast (7-12 fmol/micrograms). These
      data suggest that inhibition of vascular cGMP-PDE activity does not prevent the
      development of tolerance in vitro, but does reverse the loss of vasorelaxant
      potency to nitroglycerin via restoration of intracellular cGMP levels.

PMID- 8276064
TI  - The effects of long-term treatment with the 5-HT1A receptor agonist 8-OH-DPAT and
      the 5-HT2/1C receptor agonist DOI in the neonatal rat.
AB  - The rat pup ultrasonic call was used to study the effects of acute and long-term
      treatment with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin
      (8-OH-DPAT) and the 5-HT2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane (DOI) during the neonatal period. Acute administration of 8-OH-DPAT
      and DOI reduced the number of ultrasonic calls. The reduction induced by 8-OH
      DPAT and DOI was antagonized by the 5-HT1A antagonist (S)-5-fluoro-8-hydroxy-2
      (di-n-propylamino)tetralin ((S)-UH-301) and the 5-HT2 antagonist ketanserin,
      respectively. The long-term treatments were started on postnatal day 1. On
      postnatal day 7, the response of the long-term DOI-treated group was clearly
      attenuated in comparison to that of the acute DOI-treated group. In contrast, no
      tolerance to the effect of 8-OH-DPAT was achieved after an analogous treatment.
      The data indicate that there is a diversity in the ontogeny of the ability to
      develop tolerance to 5-HT1A agonists in comparison to 5-HT2/1C agonists.

PMID- 8276065
TI  - Methamphetamine antagonistic property of (+)- and (-)-4
      phenyltetrahydroisoquinoline in rat anococcygeus muscle.
AB  - The antagonistic effects of (+)- and (-)-4-phenyl-1,2,3,4-tetrahydroisoquinoline
      (4PTIQ) on methamphetamine in the rat anococcygeus muscle were compared with
      those of cocaine and nomifensine. Methamphetamine contracted the anococcygeus
      muscle through the release of norepinephrine from noradrenergic nerve terminals.
      (+)-4PTIQ inhibited the methamphetamine-induced contractions more strongly than
      cocaine and nomifensine. (+)-4PTIQ had no potentiating effects on exogenous
      norepinephrine-induced contraction, which was considered to be an index of amine
      neuronal uptake blockade. On the other hand, (-)-4PTIQ, cocaine and nomifensine
      produced a significant leftward shift of the norepinephrine concentration
      response curve, i.e. they showed a strong blocking effect on amine neuronal
      uptake. These results suggest that the inhibitory effects of (+)-4PTIQ on the
      action of methamphetamine are mediated by a mechanism other than inhibition of
      amine neuronal uptake.

PMID- 8276066
TI  - Effects of 7-hydroxy-N,N-di-n-propylaminotetralin on behaviour and blood pressure
      of spontaneously hypertensive rats.
AB  - The in vivo effects of administration of the putative dopamine D3 receptor
      agonist 7-hydroxy-N,N-di-n-propylaminotetralin (7-OH-DPAT) were investigated in
      spontaneously hypertensive rats (SHR) and normotensive wistar-Kyoto controls
      (WKY). The i.p. injection of 7-OH-DPAT induced hyperactivity in WKY at 10 mg/kg,
      but only an inhibition of exploratory locomotor activity was observed in SHR at 1
      mg/kg. In WKY and SHR with unilateral lesions of the nigrostriatal system, s.c.
      injection of 0.01-1 mg/kg of 7-OH-DPAT induced dose-dependent contralateral
      turning behaviour. This response was more pronounced in SHR than in WKY. The s.c.
      injection of 0.03, but not of 0.01 or 0.1 mg/kg, of 7-OH-DPAT induced yawning in
      WKY and SHR. The i.v. injection of 0.1 or 1 mg/kg of 7-OH-DPAT induced an
      immediate rise in blood pressure in both WKY and SHR. Pretreatment with the
      dopamine receptor antagonist haloperidol partially prevented this pressor
      response and, in addition, unmasked a late fall in blood pressure in SHR. The
      s.c. injection of 1 mg/kg of 7-OH-DPAT induced a decrease in body temperature,
      which was more pronounced in SHR than in WKY. This effect could be inhibited by
      pretreatment with haloperidol, but a residual hypothermia remained in SHR. These
      results suggest that 7-OH-DPAT induces a variety of effects in vivo, many of
      which may be mediated by dopamine D2 receptors or non-dopaminergic receptors.
      Thus, more selective dopamine D3 receptor agonists or -antagonists are needed to
      further explore the role of dopamine D3 receptors in vivo.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8276067
TI  - The anti-platelet actions of FR122047, a novel cyclooxygenase inhibitor.
AB  - The anti-platelet actions of 1-[(4,5-bis(4-methoxyphenyl)-2- thiazoyl)carbonyl]-4
      methylpiperazine hydrochloride (FR122047) were investigated in vitro and in vivo.
      FR122047 was 100 times more potent than aspirin against arachidonic acid- and
      collagen-induced human and guinea-pig platelet aggregation in vitro. Its actions
      on platelets were a result of cyclooxygenase inhibition. The single oral dose of
      FR122047 inhibited arachidonic acid- and collagen-induced aggregation with an
      ED50 of 280 micrograms/kg and 530 micrograms/kg, respectively, in guinea-pigs.
      The anti-platelet action was augmented 5-10 times by repeated administration for
      4 days. At 1 mg/kg the inhibitory actions were prolonged for 48 h and the drug
      concentration was < 0.1 ng/ml in platelet-poor plasma at 24 h and 0.282 ng/ml in
      platelet-rich plasma at 48 h. The safety margin in rats (minimum ulcerogenic
      dose/ED50 for anti-platelet aggregation) of FR122047 was more than 70, while that
      of aspirin was only 1.2. These results indicate that FR122047 is concentrated in
      platelets and may be a useful anti-platelet agent.

PMID- 8276068
TI  - Changes in islet glucan-1,4-alpha-glucosidase activity modulate sulphonylurea
      induced but not cholinergic insulin secretion.
AB  - We have previously presented indirect in vivo evidence for the involvement of
      islet acid glucan-1,4-alpha-glucosidase (acid amyloglucosidase), a lysosomal
      glucose-producing enzyme, in certain insulin secretory processes. In the present
      in vitro and in vivo investigation, we studied whether differential changes in
      islet acid amyloglucosidase activity would be related to the insulin secretory
      response induced by two mechanistically different secretagogues, the
      sulphonylurea derivative, glibenclamide and the acetylcholine receptor agonist,
      carbachol. It was observed that the selective alpha-glucosidehydrolase inhibitors
      emiglitate and acarbose markedly reduced glibenclamide-induced insulin release
      from isolated islets. Insulin release stimulated by carbachol or the protein
      kinase C activator TPA (12-O-tetradecanoylphorbol 13-acetate), was not inhibited.
      Basal insulin secretion was unaffected by emiglitate and acarbose. Further,
      pretreatment of mice with emiglitate resulted in a marked reduction of the in
      vivo insulin response to glibenclamide. Moreover, in vivo pretreatment with
      purified fungal amyloglucosidase ('enzyme replacement'), a procedure known to
      increase islet amyloglucosidase activity, greatly enhanced the insulin response
      to i.v. glibenclamide. This insulin release was accompanied by a marked
      depression of the blood glucose levels. In contrast, enzyme pretreatment did not
      influence the insulin response or the blood glucose levels after carbachol. The
      data strongly suggest that islet acid amyloglucosidase is involved in the insulin
      secretory processes induced by glibenclamide but not in those involving
      stimulation of muscarinic receptors or direct activation of protein kinase C. The
      results also indicate separate or at least partially separate pathways for
      insulin release induced by glibenclamide and cholinergic stimulation.

PMID- 8276069
TI  - Endothelial thromboxane production plays a role in the contraction caused by 5
      hydroxytryptamine in rat basilar arteries.
AB  - The goal of the present study was to characterize the role of the endothelium in
      the 5-hydroxytryptamine (5-HT)-induced contraction of the rat basilar artery. Rat
      basilar artery segments were mounted in myographs to study their isometric
      tension development. 5-HT caused dose-dependent contractions that were minimally
      affected by endothelium removal. The dose-response curve obtained with the 5-HT1
      receptor agonist, 5-carboxamidotryptamine (5-CT), was biphasic in arteries with
      endothelium; removal of the endothelium eliminated the first phase of the
      contraction. The 5-HT2 receptor antagonist, ketanserin (30 nM), shifted the dose
      response curve to 5-HT to the right; in arteries with endothelium, the curve
      became biphasic. Ketanserin inhibited the second phase of the dose-response curve
      to 5-CT. The mixed 5-HT1/5-HT2 receptor antagonist, metergoline (30 nM), shifted
      the dose-response curve to 5-HT non-competitively to the right and depressed both
      phases of the dose-response curve to 5-CT. In basilar arteries with endothelium
      and treated with ketanserin, the thromboxane A2 receptor antagonist, ICI 192605
      (1 microM), significantly decreased the responsiveness to 5-HT and the dose
      response curve for 5-HT became monophasic. ICI 192605 and the thromboxane A2
      synthase inhibitor, ridogrel (10 microM), both suppressed the first phase of the
      dose-response curve to 5-CT. These data indicate that both endothelial 5-HT1 and
      smooth muscle 5-HT2 receptors participate in the contractions caused by 5-HT in
      the rat basilar artery.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276070
TI  - Cocaine and several sigma receptor ligands inhibit dopamine uptake in rat caudate
      putamen.
AB  - Cocaine and several sigma receptor ligands inhibit dopamine uptake via a common
      site. This is evidenced by a concentration-dependent inhibition of dopamine
      uptake and displacement of the binding of [3H]WIN 35,428 (also called CFT), a
      cocaine analog with high affinity for the dopamine transporter. Since several
      sigma receptor ligands have been shown to block the stimulant effects of cocaine,
      this site may serve as a target for future drug development to treat cocaine
      abuse.

PMID- 8276071
TI  - Potentiation of norepinephrine-induced contraction by primary prostaglandin
      receptor activation in rat aorta.
AB  - This study investigates the role of primary prostaglandin receptor activation in
      the modulation of agonist-induced vascular smooth muscle contraction.
      Prostaglandin F2 alpha induced a concentration-dependent contraction of the rat
      aorta that was nearly abolished by the thromboxane A2 receptor antagonist,
      SQ29548. Prostaglandin F2 alpha in the presence of SQ29548 induced leftward
      shifts of the norepinephrine and KCl concentration-response curves. Nifedipine
      abolished the leftward shift of the norepinephrine concentration-response curve
      observed in the presence of prostaglandin F2 alpha and SQ29548. These results
      suggest that a function of primary prostaglandin receptor activation may be to
      potentiate agonist-induced contraction. The potentiation is dependent upon the
      opening of dihydropyridine-sensitive Ca2+ channels.

PMID- 8276072
TI  - Differential effects of Mandevilla velutina compounds on paw oedema induced by
      phospholipase A2 and phospholipase C.
AB  - This study compares the effect of Mandevilla velutina compounds with some anti
      inflammatory drugs against phospholipase A2- and phospholipase C-induced rat
      hindpaw oedema. Injection of phospholipase A2 (Naja naja, 2.5-20 U/paw) and
      phospholipase C (Clostridium perfringens, 0.03-0.05 U/paw) caused a dose-and-time
      related increase in paw oedema. Compounds MV 8608 (55 mumol/kg) and MV 8612 (32
      mumol/kg, i.p.) inhibited phospholipase A2-induced paw oedema without interfering
      with phospholipase C-induced oedema. Local injection of both M. velutina
      compounds also partially attenuated the oedema evoked by phospholipases A2 and C.
      Dexamethasone (1.3 mumol/kg, p.o.) suppressed only phospholipase A2-induced paw
      oedema, while indomethacin (11 mumol/kg, p.o.) attenuated only the early phase of
      phospholipase C-induced oedema. By contrast, phenidone (616 mumol/kg, i.p.)
      inhibited only phospholipase C-induced oedema, while cyproheptadine (31 mumol/kg)
      and pyrilamine (100 mumol/kg, p.o.) inhibited only phospholipase A2 oedema.
      Treatment of animals with compound 48/80 markedly suppressed phospholipase A2
      induced paw oedema and to a lesser degree the oedema caused by phospholipase C.
      Our results indicate that there are marked differences regarding the mechanisms
      underlying the paw oedema responses caused by phospholipase A2 and phospholipase
      C. In addition, our data show that M. velutina compounds cause potent and long
      lasting inhibition of the pro-inflammatory action of phospholipase A2, an effect
      which may account for their reported anti-inflammatory activities.

PMID- 8276073
TI  - Involvement of vagal pathway in the anti-secretory effect of a novel xanthine
      derivative.
AB  - The inhibitory action of a novel xanthine derivative, 3-ethyl-1-(6-hydroxy-6
      methylheptyl)-7-propylxanthine (A90 6119) on gastric acid secretion was studied
      in rats. In conscious pylorus-ligated rats, A90 6119 (3 mg/kg intraduodenally,
      i.d.), inhibited gastric acid output stimulated by carbachol and by 2-deoxy-D
      glucose by 49% and 100% respectively. Basal acid secretion was inhibited by 61%
      by 10 mg/kg, i.d. A90 6119. In urethane anesthetized stomach-lumen-perfused rats,
      A 90 6119 at 1 and 3 mg/kg, i.d. significantly reduced the acid secretion
      stimulated by 2-deoxy-D-glucose, by 83% and 100%, respectively. The stable
      thyrotropin-releasing hormone (TRH) analog, RX 77368, injected intracisternally
      (i.c.) at a 30 ng dose, induced concomitant increases in acid secretion and
      gastric mucosal blood flow. A90 6119 (10 micrograms/rat, i.c.) inhibited by 93%
      and 132% the increase in acid secretion and gastric mucosal blood flow induced by
      i.c. injection of TRH analog, respectively. These data suggest that the anti
      secretory effect of A90 6119 involves inhibition of both central and peripheral
      vagal cholinergic pathways.

PMID- 8276074
TI  - 5-HT1A and 5-HT1C/1D receptor agonists produce reciprocal effects on male sexual
      behavior of rhesus monkeys.
AB  - Research has indicated that serotonin (5-HT) is involved in regulating male
      sexual behavior in rodent, as well as primate species. The present study was
      designed to further characterize 5-HT influences on male sexual behavior of
      rhesus monkeys. Experiment 1 examined the effects of 5-HT1A and 5-HT1C/1D
      receptor stimulation on penile erections and yawning behavior. Administration of
      the 5-HT1C/1D receptor agonist, m-chlorophenylpiperazine (m-CPP, 0.8 and 3.0
      mg/kg), facilitated the occurrence of penile erection, and at doses greater than
      0.2 mg/kg stimulated yawning. By contrast, the 5-HT1A receptor agonist, 8-hydroxy
      2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-0.2 mg/kg) did not significantly
      influence penile erections or yawning behavior. Experiment 2 evaluated the
      effects of m-CPP and 8-OH-DPAT on the behavior of male monkeys in the presence of
      a sexually receptive female monkey which the males could see, hear and smell, but
      not physically contact. Administration of m-CPP along with presentation of a
      receptive female stimulated penile erections to a greater extent than they were
      stimulated by either one of these manipulations alone. Administration of 8-OH
      DPAT (0.1 and 0.2 mg/kg) produced a decrease in the percent of monkeys exhibiting
      penile erections in the presence of the female. In this experiment, yawning was
      affected in opposite directions, with m-CPP stimulating and 8-OH-DPAT decreasing
      the frequency of yawning. Experiment 3 assessed the effects of m-CPP on male
      copulatory behavior of rhesus monkeys. Administration of m-CPP (0.8-3.0 mg/kg)
      produced a dose-dependent decline in the percent of males initiating copulation
      and achieving ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276075
TI  - A role for platelet-activating factor in endothelin-1-induced rat mesangial cell
      proliferation.
AB  - Endothelin-1 stimulated the release of bioassayable platelet-activating factor
      like material and the incorporation of acetate to PAF in rat mesangial cells, in
      a dose-dependent manner, with an EC50 of about 10(-9) M. Endothelin-1 also
      stimulated dose dependently [3H]thymidine incorporation into DNA, protein
      synthesis and cell growth. The platelet-activating factor antagonists BN-52021
      (10(-5) M), and alprazolam (10(-5) M), reduced significantly endothelin-1
      stimulated thymidine incorporation into DNA, protein synthesis and cell growth.
      Platelet-activating factor also stimulated significantly thymidine incorporation
      into DNA, cell proliferation and protein synthesis. In conclusion, the present
      results suggest that endothelin-1 induces mesangial cell proliferation through a
      mechanism involving among others, synthesis and release of platelet-activating
      factor by these cells.

PMID- 8276076
TI  - Apparent antioxidant effect of l-deprenyl on hydroxyl radical formation and
      nigral injury elicited by MPP+ in vivo.
AB  - Using a modified microdialysis procedure, we confirmed that intrastriatal
      administration of 1-methyl-4-phenylpyridinium ion (MPP+) induced a sustained
      overflow of dopamine accompanied by increased formation of hydroxyl free radicals
      (.OH) as reflected by salicylate hydroxylation. Pretreatment with l-deprenyl
      (selegiline 60 pmol, intrastriatal perfusion) significantly decreased the .OH
      formation elicited by MPP+ (75 nmol). There was a small decrease of dopamine
      efflux and an insignificant change of the ratio of 3,4-dihydroxyphenylacetic acid
      (DOPAC)/dopamine following l-deprenyl pretreatment. These in vivo findings
      support prior in vitro data that an unique antioxidant property of l-deprenyl may
      be independent of its inhibition of type B monoamine oxidase. In addition,
      intranigral co-administration of l-deprenyl (4.2 nmol) with MPP+ (4.2 nmol)
      completely protected nigral neurons from probable oxidative injuries induced by
      MPP+ (4.2 nmol), as reflected by a near 50% loss of striatal dopamine ipsilateral
      to the side of infusion of drug into the substantia nigra. This apparent
      neuroprotective effect of l-deprenyl on midbrain nigral neurons was also
      confirmed by histological findings. The present in vivo data clearly demonstrate
      that l-deprenyl can protect nigral neurons against dopamine neurotoxicity
      produced by MPP+, as suggested by an earlier in vitro study. Thus, l-deprenyl can
      preserve the function of MPP(+)-damaged nigral neurons perhaps by its apparent
      antioxidant property in addition to its blockade of the bioactivation of 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to toxic pyridinium metabolites by
      type B monoamine oxidase.

PMID- 8276077
TI  - Strain differences in rat brain and liver sigma binding: lack of cytochrome P450
      2D1 involvement.
AB  - Substrates for cytochrome P450-2D1 exhibit a high affinity for sigma binding
      sites suggesting that sigma sites may be associated with the cytochrome P450-2D1
      isozyme. In contrast to Sprague-Dawley, Dark Agouti rat liver does not express
      the P450-2D1 gene product. Therefore, if a subpopulation of sigma sites is
      associated with the P450-2D1 enzyme, then the number (Bmax) of sigma sites is
      predicted to be decreased in Dark Agouti brain and liver compared to Sprague
      Dawley tissues. In the present study, binding of [3H](+)-3-(3-hydroxyphenyl)-N-(1
      propyl)piperidine ([3H](+)3-PPP) in brain and liver from Dark Agouti, Sprague
      Dawley, Long Evans and Wistar rat strains was examined. Results demonstrate
      marked variation in Bmax among the strains, with a consistently lower value for
      Dark Agouti tissues. However, the absolute difference in sigma binding between
      brain and liver for each strain was not consistent with reported differences in
      the activity or levels of P450-2D1. Additionally, the percentage decrease in Bmax
      for Dark Agouti liver was found to be similar to that for Dark Agouti brain.
      Taken together these results suggest that P450-2D1 does not account for the
      strain-related difference in sigma binding; but rather, other genetic factor(s)
      may be responsible for the decrease in the number of sigma sites in the Dark
      Agouti strain compared to the other rat strains examined.

PMID- 8276078
TI  - Effects of GM1 ganglioside on cardiac function following experimental hypoxia
      reoxygenation.
AB  - Rat hearts made hypoxic for 20 min by perfusion with 95% N2/5% CO2 and
      reoxygenated for 20 min in a Langerdorff apparatus showed a dose-dependent
      reduction of lactate dehydrogenase release when incubated with ganglioside GM1
      (0.1-10 microM). The decline of contractile force during hypoxia was also reduced
      dose dependently in the presence of GM1. Similar effects were observed in hearts
      obtained from animals treated i.p. with 40 mg/kg GM1 for 14 days. The levels of
      Na+,K(+)-ATPase in ventricular tissue were also reduced after hypoxia
      reoxygenation and the reduction was prevented in hearts from GM1-treated animals.
      GM1 (1-30 microM) reduced the functional response to field stimulation of
      adrenergic nerve terminals in isolated atria. Rat atria made hypoxic in glucose
      free media maintained normal stores of tissue noradrenaline in the presence of 1
      microM GM1. In the rabbit, GM1 (40 mg/kg i.p. for 4 days) reduced the alterations
      of the ST segment of the ECG during acute occlusion of the left descending and
      circumflex coronaries artery. In conclusion, ganglioside GM1 reduces some effects
      of hypoxia-reoxygenation in the heart, through still unknown mechanisms.

PMID- 8276079
TI  - The role of peripheral opioid receptor subtypes in the modulation of gastric acid
      secretion and plasma gastrin in dogs.
AB  - The peripheral opioid receptor subtypes involved in the regulation of gastric
      acid secretion were studied in dogs with both a gastric fistula and a Heidenhain
      pouch, by using the putative mu-opioid receptor agonist dermorphin, the delta
      opioid receptor agonist [D-Ala2,D-Leu5]enkephalin (DADLE) and the kappa-opioid
      receptor agonist dynorphin-(1-13). Dermorphin caused a significant increase in
      basal acid secretion from both the gastric fistula and the Heidenhain pouch,
      while DADLE and dynorphin-(1-13) did not. Acid secretion stimulated by 2-deoxy-D
      glucose from the gastric fistula was not modified by dermorphin and dynorphin-(1
      13), while DADLE significantly inhibited it; at the same time gastric secretion
      from the Heidenhain pouch was significantly increased by dermorphin and
      unmodified by DADLE and dynorphin-(1-13). Dermorphin, DADLE or dynorphin-(1-13)
      did not modify plasma gastrin during basal or 2-deoxy-D-glucose-stimulated
      conditions. Submaximal bethanechol-stimulated secretion was increased by
      dermorphin and DADLE but unaffected by dynorphin-(1-13). Acid secretion from the
      gastric fistula stimulated by pentagastrin was enhanced by dermorphin, inhibited
      by DADLE and unaffected by dynorphin-(1-13). Dermorphin and DADLE significantly
      increased acid secretion from the Heidenhain pouch stimulated by pentagastrin,
      while dynorphin-(1-13) was ineffective. Naloxone prevented the stimulatory
      effects of dermorphin and DADLE on the Heidenhain pouch, but it reduced acid
      secretion from the gastric fistula further when given with DADLE. The inhibitory
      effects of DADLE on secretion from the gastric fistula were prevented by
      naltrindole, a selective antagonist of delta-opioid receptors.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8276080
TI  - Strong activation of vascular prejunctional beta 2-adrenoceptors in freely moving
      rats by adrenaline released as a co-transmitter.
AB  - The effect of adrenaline on the electrically evoked noradrenaline overflow in the
      portal vein of adrenal demedullated freely moving rats was studied. Adrenaline
      (100 ng/min) was infused for 2 h into the portal vein. After a 1-h interval when
      plasma adrenaline had returned to pre-infusion undetectable levels, the portal
      vein nervus plexus was electrically stimulated. During stimulation (2 Hz, 3 ms, 5
      mA) adrenaline and noradrenaline were released. The stimulus-evoked noradrenaline
      overflow was facilitated to 194% of the control-evoked overflow (infusion of
      saline). Total catecholamine overflow (noradrenaline plus adrenaline) was
      enhanced to 258%. The facilitation of the evoked overflow of both noradrenaline
      and adrenaline was blocked by the selective beta 2-adrenoceptor antagonist, ICI
      118,551 (0.3 mg/kg). Cocaine (2.5 mg/kg plus 0.05 mg/kg per min) infused together
      with adrenaline prevented the evoked release of adrenaline and no facilitation of
      the stimulus-induced noradrenaline overflow occurred. Inhibition of prejunctional
      inhibitory alpha 2-adrenoceptors with yohimbine (0.5 mg/kg) further enhanced, to
      577%, the electrically evoked catecholamine overflow after adrenaline infusion.
      The results demonstrate that adrenaline can be taken up by sympathetic nerve
      endings through cocaine-sensitive uptake carriers, and is released from these
      nerves during electrical stimulation of the portal vein nervus plexus. Neuronally
      released adrenaline can strongly facilitate electrically evoked neurotransmitter
      overflow through activation of prejunctional beta 2-adrenoceptors.

PMID- 8276082
TI  - Fluorine-18 labelled substituted benzazepines as potential radiotracers for
      imaging dopamine D1 receptors by positron emission tomography.
AB  - High affinity and selective fluorinated derivatives of 7-chloro-8-hydroxy-3
      methyl-1-(3'-aminophenyl)-2,3,4,5-tetrahydro-1H-3- benzazepine (SCH 38548) for
      dopamine D1 receptors have been prepared. The derivatives exhibit subnanomolar to
      nanomolar affinities for dopamine D1 receptors and micromolar to millimolar
      affinities for dopamine D2 and 5-HT2 receptors. Biodistribution of N-(3
      [18F]fluoropropyl)SCH 38548 in rats showed specific uptake and retention (0.64%
      injected dose/g at 30 min) of the radiotracer in the striata with striata to
      cerebellum ratios reaching 12 at 2 h post-injection. Preliminary positron
      emission tomography scans in rhesus monkeys indicate selective uptake of the
      radiotracer in the striata.

PMID- 8276081
TI  - Endothelial regulation of coronary vascular tone in vitro: contribution of
      endothelin receptor subtypes and nitric oxide.
AB  - The functional effects of endothelin-1, endothelin-3 and the ETB receptor agonist
      [Ala1,3,11,15]endothelin-1 on pig coronary arteries were characterized in vitro
      by using the ETA receptor antagonist BQ-123 and the nitric oxide synthesis
      inhibitor N-nitro-L-arginine. Endothelin-1 (EC50 value 8.8 nM), endothelin-3
      (EC50 11.6 nM) and [Ala1,3,11,15]endothelin-1 (EC50 42 nM) evoked concentration
      dependent contractions with maximal responses that were 151 +/- 21, 85 +/- 12 and
      11 +/- 2%, respectively, of contractions evoked by 127 mM K+. BQ-123 (0.1-10
      microM) induced concentration-related rightward shift of the response to
      endothelin-1. The response to the highest concentration of endothelin-1 was
      reduced by 62% in the presence of 10 microM BQ-123. Application of BQ-123 to
      vessels precontracted with endothelin-1 caused relaxation by 53%. BQ-123 also
      inhibited the contractile effect of endothelin-3, whereas the contractile
      responses to [Ala1,3,11,15]endothelin-1, serotonin or neuropeptide Y (Y1 receptor
      mediated) were unaffected. In the presence of N-nitro-L-arginine (50 microM) the
      responses to [Ala1,3,11,15]endothelin-1 and low concentrations of endothelin-3
      were significantly enhanced. The present results show that endothelin-induced
      contractions of porcine coronary arteries are efficiently prevented and reversed
      by BQ-123 indicating that the responses are evoked by ETA receptors. A portion of
      the contraction seems to be mediated by ETB receptors. The contractile response
      to ETB stimulation is in part counteracted by release of nitric oxide.

PMID- 8276083
TI  - Mucosal adenosine deaminase activity and gastric ulcer healing.
AB  - Adenosine deaminase activity was studied in gastric corpus mucosa close to an
      ulcer crater. It was found that 6 weeks of therapy with ranitidine was
      accompanied by a decrease in enzyme activity in the mucosa around healed ulcers
      and an increase around those which failed to heal. The different activities of
      adenosine deaminase in the vicinity of healed and unhealed ulcers may indicate
      its possible role in peptic ulcer healing.

PMID- 8276084
TI  - No effect of genetic obesity and mazindol on imidazoline I2 binding sites in the
      brain of Zucker rats.
AB  - The density and affinity states of imidazoline I2 binding sites as well as the
      density of alpha 2-adrenoceptors were quantitated in the brain of lean and obese
      Zucker rats. No significant differences were obtained between Zucker phenotypes
      for these receptors in the cerebral cortex and hypothalamus. Moreover, chronic
      treatment with the anorexic imidazoline derivative, mazindol, did not alter the
      density of brain imidazoline I2 binding sites. It is concluded that this genetic
      model of obesity is not associated with abnormal imidazoline I2 binding sites.

PMID- 8276085
TI  - Inhibition of cholinergic neurotransmission in isolated guinea-pig main bronchi
      by SR 48968.
AB  - SR 48968 (10(-6) to 10(-5) M) inhibited the cholinergic response of the isolated
      guinea-pig main bronchus to electrical field stimulation. Since this effect was
      reversed by naloxone 10(-5) M and since SR 48968 had no effect on the contractile
      response to exogenous acetylcholine, we conclude that SR 48968 acts at a
      prejunctional level and that opioid receptors are involved. This effect was
      observed at concentrations approximately 75,000 times higher than those needed
      for blockade of tachykinin NK2 receptors.

PMID- 8276086
TI  - [Effect of superoxide dismutase on experimental allergic uveitis].
AB  - In this study, experimental allergic uveitis (EAU) in guinea pigs was induced by
      an injection of bovine serum albumin (BSA) into the vitreous after having pre
      immunized them intradermally with BSA plus incomplete Freund adjuvant, and the
      effect of superoxide dismutase (SOD) on EAU was observed. The result showed that,
      histopathologically, the phlogistic cell infiltration and exudation within the
      anterior ocular part of the SOD- treated animals reduced notably. It is suggested
      that SOD which can scavenge the free radical superoxide anion may alleviate the
      cellular reaction in the pathological process of uveitis.

PMID- 8276087
TI  - [A histological study on peripheral iris in primary angle closure glaucoma].
AB  - Iris specimens obtained during the peripheral iridectomy in 12 cases (18 eyes) of
      primary angle closure glaucoma were studied histologically. The iris specimens
      taken during the senile cataract extraction in otherwise normal eyes were used as
      controls. The remarkable differences of the two groups are the changes of the
      quality and quantity of the mitochondria in the cells of iris tissue. The changes
      in primary glaucoma, especially in the intermittent stage of the angle closure
      glaucoma, were found in the mitochondria of the cells.

PMID- 8276088
TI  - [Intraoperative explosive choroidal hemorrhage (report of four cases)].
AB  - Intraoperative explosive choroidal hemorrhage (ECH) is a rare, but severe
      complication of intraocular surgery. This complication often occurs during or
      after intraocular surgery. We report four cases that developed this complication
      during surgery. Once the complication occurs, we should use the dehydration
      medicine intravenously, suture the incision, application of pressure directly to
      the eye and incise the postsclera. If the bleeding can't be stopped, enucleation
      is the indication.

PMID- 8276089
TI  - [Clinical observation of immunotherapy in ocular malignant tumors with lymphokine
      activated killing (LAK) cell].
AB  - In this paper, the authors reported the method of treating ocular malignant
      tumors with lymphokine-activated killing cells which were induced by rIL-2 in
      vitro. Among the sixteen cases of ocular tumors, 4 cases of 5 base cell carcinoma
      (1 case of which was partially extinctive), 4 cases of tarsal gland carcinoma, 2
      cases of squamous cell carcinoma and respectively 1 case of retinoblastoma, non
      Hodgkin's lymphoma, intraorbital hemangiopericytoma, intraorbital fibrous
      histiocytomas and hidradenocarcinoma were completely extinctive. The result shows
      that the immunotherapy method is effective.

PMID- 8276090
TI  - [Anti-retinoblastoma reaction developed in vivo through immunization of retinal
      ganglion neuronotrophic factor].
AB  - Isolated retinal ganglion neuronotrophic factor (RGNTF) was used as an antigen to
      immunize Group A Balb/c mice intraperitoneally prior to the inoculation into the
      anterior chamber of eye with human retinoblastomal cell line Y-79 (Rb). In Group
      B mice, Rb cells were inoculated into the eyes before RGNTF immunization. In
      Group C mice, empty gel without RGNTF was used in immunization 10 days after the
      Rb inoculation, to serve as a control. The results revealed that the inhibitory
      rate of Rb tumor development in Group A was 65% (13/20); in Group B only 10%
      (2/20); and in Group C 0% (0/20). The T-test for difference in the inhibitory
      rate between Group A and B was statistically significant (T > 2.58; P < 0.01).
      Sera were collected from these mice and their content of the anti-RGNTF antibody
      was quantified by ELISA method. The results showed that the anti-RGNTF antibody
      titer in Group A antisera at 1:600 dilution was measured with an average optical
      density of 0.156 +/- 0.015; that in Group B 0.103 +/- 0.016; and that in Group C
      only 0.048 +/- 0.018. Those of controls for normal mouse serum and culture medium
      were 0.050 +/- 0.008 and 0.043 +/- 0.014, respectively. The t test for difference
      in the antibody titer measurements between Group A and B was statistically
      significant (t > t0.05; p < 0.05). Therefore, the above results indicated that
      active immunization of RGNTF can enhance the specific immunity against the
      development of retinoblastomal tumor in Balb/c mice, which may have clinical
      significance in treating human retinoblastoma.

PMID- 8276091
TI  - [CT scan in 52 cases of retinoblastoma].
AB  - The results of CT scan in 52 patients (61 eyes) with retinoblastoma (Rb) managed
      and confirmed by clinical and pathological examination are reported. The features
      and value of imaging of CT scan are described and discussed. In this series,
      96.72% of cases revealed Rb and 90.16% of the cases with Rb tumor showed evidence
      of calcification on CT scan. The contrast enhancement of the tumor was slight.
      19.67% of the cases with Rb tumor showed retrobulbar extension and invaded
      intracranium (including 3 cases of intracranical tumor extension and one case of
      trilateral Rb). We think it is important to perform CT scan in suspected cases of
      Rb, and in patients with Rb invading the orbit or intracranium as well as in
      bilateral Rb. Some problems in the diagnosis and differential diagnosis are
      briefly discussed.

PMID- 8276092
TI  - [Pathologic classification of 435 primary orbital tumors].
AB  - This paper analysed the pathologic classification of 435 primary orbital tumors,
      which were mainly divided into eight types, including 83 cases (19.1%) of cystic
      lesions, 64 cases (14.7%) of vasculogenic lesions, 50 cases (11.5%) of
      mesenchymal tumors, 73 cases (16.8%) of lacrimal gland epithelial lesions, 54
      cases (12.4%) of neural tissue tumors, 55 cases (12.6%) of lymphocytic lesions,
      16 cases (3.7%) of histiocytic lesions and 40 cases (9.2%) of idiopathic orbital
      pseudotumor. The clinicopathologic characteristics of the common orbital tumors
      were also discussed.

PMID- 8276093
TI  - [The clinical use of steady-state flash visual evoked potentials].
AB  - The authors applied 30Hz flash stimuli to record steady-state flash visual evoked
      potentials (FVEP) and extracted the amplitudes and phases of the first and second
      harmonics as the characteristic value by discrete Fourier transform (DFT). 46
      normal controls (89 eyes) and 78 patients (109 eyes) were detected and analysed
      by this method. The result showed that the characteristic values of the normal
      controls are significantly different in three age groups and showed the positive
      in 35 eyes with the optic never diseases (82.9%), 25 eyes with age-related
      macular degeneration (92%), and 9 eyes with retinal detachment involved macular
      (100%). It indicates the method is a sensitive index to evaluate the macular
      visual function. After preliminary observation, the visual acuities of
      postoperation were found above 0.4 in cataracts (28 eyes) or opacities (12 eyes)
      if preoperative FVEP were normal and non-complicated, or less than 0.4 if
      preoperative FVEP were abnormal. This suggests the method is one of the effective
      index to detect the postoperative vision of the media opacities. The advantages,
      disadvantages and the clinical applications were discussed.

PMID- 8276094
TI  - [The multi-channel VEPs topography in optic neuritis].
AB  - The multi-channel VEPs topographies of 20 normal persons and 22 patients suffered
      from optic neuritis were recorded. In normal subjects, the topography showed
      symmetric distribution by full-field stimulation and paradoxical lateralization
      by half-field stimulation. In patients with optic neuritis, it showed asymmetric
      distribution most on the temperal side, some on the nasal side and occasionally
      in the middle by full-field stimulation. The result suggests that the optic nerve
      may be damaged on either temperal or nasal. The effect of the early diagnosis and
      evaluating treatment using topography is also discussed.

PMID- 8276095
TI  - [Clinical application of electro-retinographic C-wave].
AB  - We studied electro-retinographic c-wave in several fundus diseases. Compared with
      the normal controls of 65 eyes, the amplitude extinguished and lowered
      respectively were 71.4% and 25% in retinal detachment (28 eyes), 72.5% and 22.5%
      in tapetal degeneration (40 eyes), 30.8% and 38.4% in uveitis (13 eyes), 18.2%
      and 50% in high myopia (22 eyes), 8.6% and 44.3% in diabetics (70 eyes). We
      conclude that the ERG-C-wave can be a very simple and practical method for
      helping the clinical diagnosis in several obscured fundus diseases, if the
      patient cooperates.

PMID- 8276096
TI  - [Study on human gamma-crystallins: IV. Photooxidation of fetal gamma 2-crystallin
      by ultra-violet irradiation].
AB  - Human fetal gamma 2-crystallin solution was irradiated by ultra-violet (UV)
      (lambda 365 nm) at varying time, and analysed by light scattering, SDS-PAGE with
      DACM, which could specifically combine to free sulphydryl, as well as tryptophan
      fluorescence and its quenching with acrylamide. The results showed that light
      scattering of gamma 2-crystallin solution increased after 24 hour irradiation;
      SDS-PAGE reveled formation of dimer which did not have free sulphydryl and low
      molecular weight peptide of gamma 2-crystallin. The tryptophan fluorescence of
      gamma 2-crystallin decreased, and acrylamide fluorescence quenching effect did
      not show significant change. It suggested that human fetal gamma 2-crystallin
      photooxidized by UV could aggreate by disulfide and degrated to low molecular
      weight peptide, and its tryptophan were also oxidized in some degree.

PMID- 8276097
TI  - [The comparative analysis of the complications of extracapsular cataract
      extraction with and without posterior chamber intraocular lens implantation].
AB  - Three-hundred and fourteen eyes that underwent extracapsular cataract extraction
      (ECCE) were analyzed. ECCE with posterior chamber intraocular lens implantation
      (PC IOL) was performed in 168 eyes and ECCE alone was performed in 146 eyes. The
      complications and visual acuity were compared in the two groups. The PC IOL group
      showed a low incidence of complications. In addition, vitreous loss occurred in
      2.38%, cystoid macular edema occurred in 0.6%, and visual acuity recovered to 0.5
      or better in 97.62% of the eyes. The incidence of complications in the ECCE group
      was slightly higher. The postoperative visual acuity in the ECCE group was lower
      than that in PC IOL group.

PMID- 8276098
TI  - [Pathologic, electron microscopic and experimental examination of band
      keratopathy].
AB  - One hundred and thirteen cases previously diagnosed as band keratopathy were
      reexamined by light microscopy and histochemistry, 10 cases of which were studied
      by TEM and 2 cases were studied by SEM. We find that the calcium deposition
      initially occur as fine calcific particles within the cytoplasm of epithelic
      cells and in the basal membrane and bowman's layer, which aggregated to form
      calcific spherules and large calcific masses extracellularly. When 3 normal
      corneal tissues were frozen and cultured, the calcium deposition occur in the
      superficial layer of bowman's membrane and in the stromal lamellae, Authors
      suggest that the degeneration and calcific abnormal metabolism of the cell caused
      by various factors is the main pathogenesis that leads to the calcific deposit.
      The evaporation and constructive destruction of the corneal surface in the
      interpiperbral area inhibits the formation of the lacrimal membrane and results
      in deposition of calcium salts in the superficial tissue of exposed cornea in a
      band configuration. The combination of glycosaminoglycan with calcium salts is
      the dynamics of aggregation of the fine calcific particles to form the calcific
      spherules and calcific masses.

PMID- 8276099
TI  - [Histochemical studies on the glycoconjugates of experimental alkali burned
      cornea in rabbit].
AB  - The model of experimental alkali burn of cornea in rabbit was obtained using 1
      mol/L NaOH solution. After being burned for 1, 3, 7 and 14 days, the
      histochemical changes of these models were studied by using labelled concanavalin
      A (ConA-FITC) and wheat germ agglutinin (WGA-FITC). The results showed that after
      being burned, the amount of glycoconjugates interacted with these lectins
      decreased, and increased gradually after 7 days, then reached the level higher
      than that in the normal cornea. These changes were related to the recovery of
      alkali burned cornea.

PMID- 8276100
TI  - Electrons generated by photosystem II are utilized by an oxidase in the absence
      of photosystem I in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The reduction and reoxidation kinetics of the first quinone-type electron
      acceptor in photosystem II, QA-, were measured by fluorescence in a light
      tolerant, photosystem I-less strain of the cyanobacterium Synechocystis sp. PCC
      6803. In this strain, which shows excellent amplitudes of variable fluorescence,
      the rate of QA- oxidation after photoreduction of the plastoquinone pool was
      about half of that in the presence of photosystem I. However, upon addition of 5
      mM KCN, QA- decay was very slow, and the rate was comparable to that seen in the
      presence of diuron, which blocks electron transport between QA and QB. The KCN
      imposed block of QA- oxidation was removed efficiently by addition of exogenous
      quinones that can oxidize the plastoquinone pool. These results indicate that, in
      the absence of photosystem I, photosystem II-generated electrons are used very
      effectively by an oxidase located in the thylakoid; this oxidase may be a
      component of the respiratory chain.

PMID- 8276101
TI  - Modifications induced by acylphosphatase in the functional properties of heart
      sarcolemma Na+,K+ pump.
AB  - Acylphosphatase purified from cardiac muscle actively hydrolyzes the
      phosphoenzyme intermediate of heart sarcolemma Na+,K(+)-ATPase. This effect
      occurred with acylphosphatase amounts (up to 800 units/mg membrane protein) that
      fall within the physiological range and the low value of the apparent Km (0.69 x
      10(-7) M) indicates a considerable affinity of the enzyme towards this specific
      substrate. Acylphosphatase addition to purified sarcolemmal vesicles
      significantly increased the rate of Na+,K(+)-dependent ATP hydrolysis. Maximal
      stimulation, observed with 800 units/mg protein, resulted in an ATPase activity
      which was about 2-fold over basal value. The same acylphosphatase amounts
      significantly stimulated, in a similar and to an even greater extent, the rate of
      ATP driven Na+ transport into sarcolemmal vesicles. These findings lead to
      suppose that an accelerated hydrolysis of the phosphoenzyme may result in an
      enhanced activity of heart sarcolemmal Na+,K+ pump, therefore suggesting a
      potential role of acylphosphatase in the control of this active transport system.

PMID- 8276102
TI  - The human HIP gene, overexpressed in primary liver cancer encodes for a C-type
      carbohydrate binding protein with lactose binding activity.
AB  - HIP was originally identified as a gene expression in primary liver cancers, and
      in normal tissues such as pancreas and small intestine. Based on gene data base
      homologies, the HIP protein should consist of a signal peptide linked to a single
      carbohydrate recognition domain. To test this hypothesis HIP and the putative
      carbohydrate recognition domain encoded by the last 138 C-terminal amino acids,
      were expressed as glutathione-S-transferase proteins (GST-HIP and GST-HIP-142,
      respectively). Both recombinant proteins were purified by a single affinity
      purification step from bacterial lysates and their ability to bind saccharides
      coupled to trisacryl GF 2000M were tested. Our results show that HIP and HIP-142
      proteins bind to lactose, moreover the binding requires divalent cations. Thus
      the HIP protein is a lactose-binding lectin with the characteristics of a C-type
      carbohydrate recognition domain of 138 amino acids in the C-terminal region.

PMID- 8276103
TI  - cDNA structure and in situ localization of the Aplysia californica pro-hormone
      convertase PC2.

PMID- 8276104
TI  - Protein uptake into E. coli during Bdellovibrio infection. A process of reverse
      secretion?
AB  - Bdellovibrio bacteriovorus is a small bacterial parasite that infects other Gram
      negative bacteria, resides in the periplasm of the host cell, and utilizes host
      macromolecules as a source of nutrients. Evidence is summarized suggesting that
      B. bacteriovorus secretes proteases and nucleases synthesized in its own
      cytoplasm that are targeted to the cytoplasm of the host cell. Possible
      mechanisms for this trans-trimembrane protein transport process are discussed.

PMID- 8276105
TI  - Limited diffusibility of gene products directed by a single nucleus in the
      cytoplasm of multinucleated myofibres.
AB  - Two types of beta-galactosidase genes, whose products are distributed in the
      nucleus (N beta-gal) or cytoplasm (C beta-gal), were injected with fructose
      intramuscularly into the quadriceps of adult mice. Regionally restricted and
      overlapped distributions of both gene products were observed in the myofibres.
      These findings indicate that N beta-gal is incorporated into the nucleus
      responsible for its synthesis and that C beta-gal becomes located in the vicinity
      of the nucleus after its synthesis. This restricted location of C beta-gal in
      myofibres remained unchanged during the development of infant mouse muscle. Thus,
      the gene products directed by the nucleus of myofibres seem to show limited
      diffusibility, suggesting a universal localization of subcellular domains in
      myofibres.

PMID- 8276106
TI  - A brain-specific gamma subunit of G protein freed from the corresponding beta
      subunit under non-denaturing conditions.
AB  - It has generally been accepted that the beta and gamma subunits of G proteins are
      tightly associated and can only be dissociated under denaturing conditions.
      However, one form of the gamma subunit, free of the beta subunit, was isolated
      under non-denaturing conditions during the purification of beta gamma complexes
      from bovine brain. Amino acid sequence analysis revealed that the N-terminus of
      this gamma subunit was not blocked and its sequence was identical to that of a
      brain-specific gamma subunit, gamma 3. Among three forms of gamma subunits
      observed in bovine brain (gamma 2, gamma 3 and gamma 7), gamma 3 was the only
      form that was not modified at the N-terminus. Although the physiological
      significance of the free form of gamma 3 is not clear, these results suggest that
      N-terminal modification of gamma subunits may be important for interaction with
      beta subunits.

PMID- 8276107
TI  - Production of bioactive gastrin from the non-endocrine cell lines CHO and COS-7.
AB  - We made a mutated progastrin cDNA construct that contains a cleavage site (-Arg(
      4)-Arg(-3)-Lys(-2)-Arg-1) specific for the Kex2-like endoprotease furin, located
      ahead of the bioactive gastrin. For expressing the mutated progastrin cDNA, we
      used two non-endocrine cell lines, CHO and COS-7. CHO cells exhibit amidating
      enzyme activity and levels of amidation enzyme mRNA as high as those in the
      pituitary-derived endocrine cell line GH3, whereas COS-7 cells have far less
      amidating activity and lower amounts of mRNA. Mutant progastrin-expressing CHO
      cells produced mostly amidated gastrin. Gel filtration showed the size of this
      gastrin corresponded to that of the synthetic human gastrin-17. In contrast, COS
      7 cells produced glycine-extended gastrin and only a small amount of amidated
      gastrin. The difference in the amount of amidated gastrin products produced by
      the two non-endocrine cell lines is due to differing amounts of the amidation
      enzyme contained in each cell line.

PMID- 8276108
TI  - Replication of adenovirus DNA in vitro is ATP-independent.
AB  - Using a reconstituted system for adenovirus DNA replication we tested the
      requirements for ATP and divalent cations. At the standard Mg2+ concentration ATP
      stimulated initiation 5 to 10-fold. However, this effect was caused by complexing
      Mg2+. At the optimal Mg2+ concentration ATP was not required for initiation or
      elongation. Besides Mg2+ also Mn2+, Ca2+ and Ba2+ were shown to support
      initiation whereas for elongation only Mg2+ was accepted. Since Mn2+ could
      efficiently be used for DNA chain elongation on synthetic templates we
      hypothesize that Mg2+ is essential for the transition of initiation to
      elongation.

PMID- 8276109
TI  - Determination of the number of detergent molecules associated with the reaction
      center protein isolated from the photosynthetic bacterium Rhodopseudomonas
      viridis. Effects of the amphiphilic molecule 1,2,3-heptanetriol.
AB  - Detergent-free reaction center (RC) proteins from the photosynthetic bacterium
      Rhodopseudomonas viridis were obtained using Bio-Beads SM-2. With these RCs, the
      amount of detergent molecules associated with the protein was measured by
      determining the detergent concentration at which re-solubilization occurred as a
      function of the RC concentration. For N,N-dimethyl dodecylamine-N-oxide (LDAO),
      Triton X-100 and beta-octylglucoside 260 +/- 30,105 +/- 10 and 360 +/- 100
      detergent molecules were necessary to dissolve the protein, respectively. With
      this technique we have studied the effect of the amphiphilic molecule 1,2,3
      heptanetriol, which is essential in the crystallization process of these RCs.
      Addition of 5% 1,2,3-heptanetriol reduces the value for LDAO to 120 +/- 20
      LDAO/RC, supporting the notion that crystallization of the RCs is promoted by
      increasing the number of protein-protein contacts.

PMID- 8276110
TI  - Conformational rearrangements required of the V3 loop of HIV-1 gp120 for
      proteolytic cleavage and infection.
AB  - HIV gp120 is specifically cleaved at a single site in the V3 loop between Arg315
      and Ala316 by thrombin. Previous observations by others have indicated that
      binding to CD4 enhances the rate of V3 loop cleavage, and that this cleavage is a
      prerequisite for HIV infection. Other observations also suggest that the cleavage
      site is in a type II beta-turn centered at Pro313-Gly314. However, our docking
      experiments indicate that this conformation cannot dock to thrombin and other
      trypsin-like serine proteases. Thus, based on the thrombin-bound conformation of
      peptide substrates, we propose that CD4 binding, at a site remote from the V3
      loop, induces and stabilizes a trans to cis isomerization of the highly conserved
      residue Pro313, and that this conformational shift is a prerequisite for cleavage
      by a 'thrombin-like' cellular protease and subsequent infection.

PMID- 8276111
TI  - Intracellular free calcium level and its response to cAMP stimulation in
      developing Dictyostelium cells transformed with jellyfish apoaequorin cDNA.
AB  - A new method is described for measuring intracellular free calcium
      concentrations, [(Ca2+)i], in the cells of Dictyostelium discoideum transformed
      with apoaequorin cDNA of the jellyfish, Aequorea victoria. Aequorin, a calcium
      specific indicator, was regenerated in vivo from apoaequorin produced in the
      cells by incubation with coelenterazine. The results showed that [(Ca2+)i] in
      developing cells markedly increases at the aggregation stage and again at the
      culmination stage after a temporary drop at the migration stage. Except for the
      vegetative stage, the cells at all stages of development exhibit a sharp
      transient increase in [(Ca2+)i] upon stimulation with a cAMP (50 nM) pulse, high
      responses being observed at the migration and culmination stages. Separated
      prestalk cells of migrating slugs contain more than twice as much [(Ca2+)i] and
      show three times as large a response to cAMP stimulation as prespore cells.

PMID- 8276112
TI  - Presence of gene expression of vitamin D receptor and 24-hydroxylase in OK cells.
AB  - We investigated the gene expression of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3)
      receptors (VDR) and 25-hydroxy-vitamin D3-24-hydroxylase (24-hydroxylase) in
      opossum kidney (OK) cells. Reverse transcription-polymerase chain reaction
      demonstrated the presence of VDR gene expression in OK cells. Northern
      hybridization, using rat VDR cDNA, also demonstrated a 4.4 kbp VDR mRNA
      expression which was affected by serum but not by 1,25(OH)2D3 and/or parathyroid
      hormone stimulation. Stimulation with 1,25(OH)2D3 induced 24-hydroxylase mRNA
      expression which peaked at 6 h. This study clearly demonstrates for the first
      time the presence of VDR and 24-hydroxylase gene expression in OK cells,
      suggesting that OK cells are a useful model for investigating the genetic action
      mechanisms of 1,25(OH)2D3.

PMID- 8276113
TI  - A novel plant glutathione peroxidase-like protein provides tolerance to oxygen
      radicals generated by paraquat in Escherichia coli.
AB  - Citrus salt-stress associated protein (Cit-SAP) reveals significant sequence
      homology to mammalian glutathione peroxidase (GP). In an attempt to assign
      biological function to this protein, transformed E. coli cells expressing Cit-SAP
      were examined for their ability to tolerate free radicals formed by paraquat, an
      O2- radical forming agent. In the presence of paraquat, the survival rate of the
      transformed bacteria expressing Cit-SAP was much higher as compared to the wild
      type bacteria. The results support the assumption that Cit-SAP is a plant GP-like
      protein which participate in the enzymatic system aimed at scavenging oxygen free
      radicals in plants.

PMID- 8276114
TI  - Mitochondrial ATP hydrolysis and ATP depletion in thymocytes and Ehrlich ascites
      carcinoma cells.
AB  - When Ehrlich ascites carcinoma (EAC) cells and thymocytes were treated with
      uncoupler or rotenone in glucose-free medium, rapid ATP depletion was observed in
      both types of the cells. Oligomycin slowed down ATP loss in thymocytes, but not
      in EAC cells. Thus, mitochondrial ATP hydrolysis appears to be significant in
      deenergized thymocytes in contrast to EAC cells, in which other ATP consuming
      reactions were prevailing. Complete deenergization of mitochondria by uncoupler
      or rotenone in these cells resulted in inactivation of mitochondrial ATPase by 65
      75%. The effect was observed after complete and rapid (20-30 s) disruption of the
      cells with detergent, Lubrol WX. ATPase was blocked by the specific inhibitor
      protein (IF1) as it was shown by the studies on reactivation of this enzyme. When
      respiration is blocked but ATP content is supported by glycolysis, mitochondrial
      ATPase is not suppressed by IF1, and maintains the energization of mitochondria.
      It is concluded that under complete de-energization of mitochondria IF1
      significantly inhibits mitochondrial ATP hydrolysis and may slow down ATP loss in
      thymocytes and EAC cells.

PMID- 8276115
TI  - Processing of prodynorphin by the prohormone convertase PC1 results in high
      molecular weight intermediate forms. Cleavage at a single arginine residue.
AB  - Processing of rat prodynorphin (proDyn) by the mouse prohormone convertase PC1
      was investigated. Recombinant vaccinia virus vectors were used to coexpress
      proDyn and PC1 in rat PC12 pheochromocytoma and mouse AtT-20 corticotroph cells.
      In vitro experiments were also conducted by co-incubating purified proDyn and
      PC1. The results demonstrate that PC1 cleaves proDyn at pairs of basic residues
      to yield 10 and 16 kDa high molecular weight (HMW) intermediates. Additionally,
      PC1 cleaves proDyn at a single arginine residue to yield an 8 kDa product and the
      C-peptide. This demonstrates that PC1 cleaves proDyn at single and pairs of basic
      residues.

PMID- 8276116
TI  - The transglycosylation reaction of cyclodextrin glucanotransferase is operated by
      a Ping-Pong mechanism.
AB  - A new photometric assay of the disproportionation activity of cyclodextrin
      glucanotransferase (CGTase) using 3-ketobutylidene-beta-2-chloro-4-nitrophenyl
      maltopentaoside as the donor, proved that the transglycosylation reaction of
      CGTase was operated by a Ping-Pong Bi Bi mechanism. The values of the
      kcat/Km(acceptor) proved that the same configurations of free hydroxyl groups
      with those of D-glucopyranose at C2, C3 and C4 positions were required for the
      acceptors used by CGTase. The structure around C6 on acceptors was not essential
      for acceptor function, but it was recognized by CGTase, since the values of
      kcat/Km for D-xylose were smaller than that for D-glucose. The value of kcat/Km
      for maltose was about 20-times larger than that for D-glucose, indicating that at
      least two glucopyranosyl rings are recognized by the acceptor binding sites.

PMID- 8276117
TI  - Cyclic AMP downregulates c-myc expression by inhibition of transcript initiation
      in human B-precursor Reh cells.
AB  - In the human pre-B cell line Reh, activation of the cyclic AMP signal
      transduction pathway induces a rapid, transient 10-fold down-regulation of steady
      state c-myc mRNA. We have investigated the mechanisms involved in this cAMP
      mediated regulation of c-myc expression. Forskolin did not alter c-myc mRNA
      stability. Initiation of c-myc transcripts was strongly inhibited after 1 h of
      forskolin treatment, as measured by nuclear run-on assays. Reinitiation of c-myc
      transcription was apparent after 3-4 h, and full transcriptional elongation was
      detected after 8 h of forskolin treatment. These data suggest that cyclic AMP
      downregulates c-myc expression by inhibition of transcriptional initiation.

PMID- 8276118
TI  - Isolation and characterization of a gene for a ryanodine receptor/calcium release
      channel in Drosophila melanogaster.
AB  - The nucleotide sequence of a 25.7 kilobase Drosophila melanogaster genomic DNA
      segment containing a gene for a ryanodine receptor/calcium release channel
      homologue has been determined. Computer analysis and partial cDNA cloning
      revealed 26 exons comprising the protein-coding sequence in this gene. The
      predicted protein is homologous in amino acid sequence and shares characteristic
      structural features with the mammalian ryanodine receptors. In blot hybridization
      analysis, a approximately 16 kilobase RNA species was identified abundantly in a
      6-12 h embryo as the transcript from this gene. In situ hybridization to polytene
      chromosomes indicated that this gene locates at band position 44F on the second
      chromosome.

PMID- 8276119
TI  - Structure of partially-activated E. coli heat-labile enterotoxin (LT) at 2.6 A
      resolution.
AB  - Biological toxicity of E. coli heat-labile enterotoxin and the closely related
      cholera toxin requires that the assembled toxin be activated by proteolytic
      cleavage of the A subunit and reduction of a disulfide bond internal to the A
      subunit. The structural role served by this reduction and cleavage is not known,
      however. We have crystallographically determined the structure of the E. coli
      heat-labile enterotoxin AB5 hexamer in which the A subunit has been cleaved by
      trypsin between residues 192 and 195. The toxin is thus partially activated, in
      that it has been cleaved but the disulfide bond has not been reduced. The
      structure of the A subunit in the cleaved toxin is substantially the same as that
      previously observed for the uncleaved AB5 structure, suggesting that although
      such cleavage is required for biological activity of the toxin it does not by
      itself cause a conformational change.

PMID- 8276120
TI  - Import of a mitochondrial presequence into P. denitrificans. Insight into the
      evolution of protein transport.
AB  - According to the endosymbiont hypothesis, mitochondria are descended from ancient
      aerobic bacteria that were engulfed by protoeukaryotic cells. Experiments
      described here show that a synthetic peptide corresponding to a yeast
      mitochondrial targeting sequence can be imported into Paracoccus denitrificans, a
      soil bacterium thought to be closely related to the protomitochondrion. The
      import is very similar to that observed with isolated yeast mitochondria. The
      results suggest that the protomitochondrion may have been inherently able to
      translocate mitochondrial presequences. This ability may partly explain the
      development of the protein import process during the evolution of the
      mitochondrion.

PMID- 8276122
TI  - Both type I and type II interferons down-regulate human tumor necrosis factor
      receptors in human hepatocellular carcinoma cell line Hep G2. Role of protein
      kinase C.
AB  - It is well known that interferon-gamma (IFN-gamma; type II) potentiates various
      responses of human tumor necrosis factor (TNF) in a wide variety of cells and
      that this potentiation is accompanied by the up-regulation of TNF receptor
      synthesis. In the present studies we examined the regulation of TNF receptors by
      type I and type II IFNs in a hepatocellular carcinoma cell line, HEP G2. Exposure
      of these cells to IFN-gamma led to a decrease in TNF receptor number (4029 vs.
      2719 sites/cell) without any change in the receptor affinity (0.96 nM vs. 1.1
      nM). The effect was time and dose-dependent. Like IFN-gamma, IFN-alpha and IFN
      beta (type I) down-modulated the TNF receptors on these cells. The effect of IFNs
      on the TNF receptors was inhibited by staurosporin, a protein kinase C (PK-C)
      inhibitor. Furthermore, by the use of receptor-specific antibodies, we found that
      the IFN-dependent decrease was primarily due to the p60 form of the TNF receptor.
      Our results presented are the first to demonstrate that IFNs can also down
      modulate TNF receptors in certain cells and that this effect is mediated through
      PK-C.

PMID- 8276121
TI  - Molecular cloning, nucleotide sequence and expression of a Sulfolobus
      solfataricus gene encoding a class II fumarase.
AB  - Fumarase catalyzes the interconversion of L-malate and fumarate. A Sulfolobus
      solfataricus fumarase gene (fumC) was cloned and sequenced. Typical
      archaebacterial regulatory sites were identified in the region flanking the fumC
      open reading frame. The fumC gene encodes a protein of 438 amino acids (47,899
      Da) which shows several significant similarities with class II fumarases from
      both eubacterial and eukariotic sources as well as with aspartases. S.
      solfataricus fumarase expressed in Escherichia coli retains enzymatic activity
      and its thermostability is comparable to that of S. solfataricus purified enzyme
      despite a 11 amino acid C-terminal deletion.

PMID- 8276123
TI  - Prolactin acts on the extreme 5' portion of MMTV LTR involving a mammary cell
      specific enhancer.
AB  - We have previously shown that a human mammotropic polypeptide hormone, prolactin
      (PRL) can act synergistically with steroid hormones to regulate gene expression
      directed by the long terminal repeat of mouse mammary tumor virus (MMTV LTR) in a
      human ductal carcinoma cell line T47D cells using a chloramphenicol
      acetyltransferase reporter gene system and gene transfection methods. In the
      present study, using various recombinant plasmids we analyzed functional elements
      in the MMTV LTR that is essential for the PRL responses. We show that the PRL
      responsive elements are located in the extreme 5' end of the MMTV LTR, a region
      previously described by others to be a mammary cell-specific enhancer.

PMID- 8276124
TI  - Expression of the genes encoding basic fibroblast growth factor and its receptor
      in human granulosa cells.
AB  - The role of basic fibroblast growth factor (bFGF) in granulosa cell ontogeny has
      been previously demonstrated. In this study we evaluated the possible
      intraovarian origin of bFGF. Human granulosa cells were maintained in primary
      culture and their cytoplasmic extract was purified by affinity chromatography on
      a heparin-sepharose column. The column was then eluted with 10 mM Tris-HCl
      containing increasing concentrations of NaCl. The chromatographic fractions were
      tested in a bioassay using bovine adrenal capillary endothelial cells (ACE) as
      targets. A peak of mitogenic activity was detected in the fraction eluted with
      the highest salt concentration. This chromatographic profile is similar to that
      of bFGF. The in situ synthesis of this bFGF-like protein was then demonstrated by
      reverse transcription-polymerase chain reaction. Using oligonucleotide primers
      specific for the bFGF gene, a single major band of DNA, corresponding to the
      expected size, was amplified. The identity of this fragment with the bFGF
      corresponding sequence was further demonstrated by restriction enzyme analysis.
      Moreover, RT-PCR was also employed to amplify a DNA band specific for the bFGF
      receptor gene. These data indicate that human granulosa cells are able to
      synthesize both bFGF and its receptor and, thus, bFGF might participate to the
      autocrine mechanisms regulating their growth and differentiated functions.

PMID- 8276125
TI  - Vitamin D receptor quantitation in human blood mononuclear cells in health and
      disease.
AB  - Vitamin D receptor (VDR) concentration was quantitated in human peripheral blood
      mononuclear cells (PBMC) from patients with absorptive hypercalciuria (AH) and
      patients with high 1,25(OH)2D3 due to acquired or transient disease states and
      the results compared to those in normal subjects. VDR concentration in resting
      cells was not different between the three groups and represented constitutive
      receptor expression of monocytes. Following activation with phytohemagglutinin,
      patients with hypercalcitriolemia demonstrated significantly greater VDR
      concentrations. Patients with AH demonstrated a normal value for the group, but 6
      patients had significantly greater concentrations of VDR despite normal plasma
      1,25(OH)2D3 in four of the patients. Proliferation, as assessed from
      [3H]thymidine incorporation was inversely correlated with serum 1,25(OH)2D3 and
      was significant (R = -0.299, p = 0.048). Taken together, the results suggest that
      PBMC provide a useful system for studying VDR status in transient or acquired
      states of hypercalcitriolemia. Furthermore, the studies in patients with
      absorptive hypercalciuria disclosed it to be a heterogeneous disorder,
      characterized by both vitamin D-dependent and D-independent forms of receptor up
      regulation.

PMID- 8276126
TI  - Insulin receptor and insulin sensitivity in a chicken hepatoma cell line.
AB  - Insulin receptors have been characterized in a cell line recently isolated from a
      chicken hepatoma (LMH). The binding of 125I-insulin to LMH cells or membranes
      displayed the expected criteria for insulin receptors: affinity, temperature
      dependency, curvilinearity of Scatchard plot, rank order of potency for insulin
      analogs and insulin induced down-regulation. The alpha-subunit of LMH cell
      insulin receptors exhibited a normal size of 135 kDa. Following
      autophosphorylation, LMH WGA-purified receptors revealed a 95 kDa beta-subunit
      and a 72 kDa protein (pp72). Both proteins were phosphorylated in a time-,
      insulin- (and insulin-like growth factor 1; IGF-1) and manganese-dependent
      manner, and were precipitated by antiphosphotyrosine and two anti-insulin
      receptor antibodies. The 72 kDa protein was not present under non-reducing
      condition PAGE or in normal chicken liver. These results strongly suggest that
      pp72 is either a truncated form of the insulin receptor beta-subunit specific to
      LMH cells or a degradation product. Lectin-purified insulin receptors from LMH
      cells or chicken liver membranes exhibited similar tyrosine kinase activity,
      using artificial substrate poly(Glu-Tyr) 4:1. Finally, amino acid uptake by LMH
      cells was insulin stimulatable.

PMID- 8276127
TI  - Triiodothyronine (T3) modulates hCG-regulated progesterone secretion, cAMP
      accumulation and DNA content in cultured human luteinized granulosa cells.
AB  - Ample clinical evidence indicates that women with thyroid disorders frequently
      exhibit menstrual disturbances and impaired fertility. In order to characterize
      the nature of thyroid hormone action in the ovary, the direct effects of
      triiodothyronine (T3) were investigated in vitro using a culture system of human
      luteinized granulosa cells. The presence of T3 receptors was also searched in
      such cells. The cell cultures were maintained in serum-free Ham's F-10 medium in
      the absence or presence of hCG, with or without graded doses of T3 (10(-11)-10(
      7) M), and cell proliferation (assessed by DNA content) as well as cell function
      (cAMP accumulation and progesterone secretion) determined. T3 alone stimulated
      cell proliferation. hCG, on the other hand, was anti-mitogenic and T3 combined
      with hCG inhibited cell growth even further, reaching levels below those reached
      by either control or hCG alone. Exposure of cells to T3 markedly enhanced hCG
      induced cAMP accumulation. Addition of 1-methyl-3-isobutylxanthine (MIX)
      abolished the cAMP-stimulatory effect elicited by T3, suggesting that the thyroid
      hormone may act, as MIX, by inhibiting phosphodiesterase. T3 was devoid of any
      influence on basal progesterone secretion, but inhibited hCG-induced secretion of
      the steroid. The effects of T3 are not accounted for by changes in cell number
      since the influence of thyroid hormone on cAMP and steroid secretion were
      expressed per microgram DNA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276128
TI  - 1,25(OH)2D3 increases cytotoxicity and exocytosis in lymphokine-activated killer
      cells.
AB  - The effect of 1,25-dihydroxyvitamin D3 on lymphokine-activated killer (LAK) cells
      activity was studied. Treatment of LAK cells with 1,25-dihydroxyvitamin D3 for 24
      h increased their cytotoxic activity without affecting cell proliferation. This
      effect was dose-dependent, detectable already at 10(-11) M attaining 44 +/- 7%
      increase at 10(-8) M. 1,25-dihydroxyvitamin D3 increased LAK cell content of the
      cytotoxic granule granzyme A by 21%. Secretion of granzyme A by LAK cells was
      triggered by 12-O-tetradecanoylphorbol 13-acetate and the calcium ionophore
      A23187. 1,25-dihydroxyvitamin D3 decreased the lag preceding secretion, increased
      the rate constant of exocytosis and the fraction of granzyme A cell content
      secreted. The potentiation of exocytosis was more pronounced at suboptimal
      calcium ionophore concentration suggesting that 1,25-dihydroxyvitamin D3 affects
      a calcium-dependent process. Since exocytosis of cytotoxic granules is a pivotal
      event in the killing of tumor cells by LAK cells, it is plausible that the
      enhancement of this process underlies the stimulation of LAK cell cytotoxic
      activity by 1,25-dihydroxyvitamin D3.

PMID- 8276129
TI  - Effects of adenosine analog PIA (n-phenylisopropyladenosine) on FSH-stimulated
      cyclic AMP (cAMP) production in the rat seminiferous epithelium.
AB  - In rat seminiferous epithelium, FSH-stimulated cAMP production is cyclically
      modulated by spermatogenic cells and is highest in stages XIV-V and lowest in
      stages VII-VIII of the epithelial cycle. Adenosine has been proposed to be an
      inhibitory paracrine molecule in Sertoli cells. In this paper the effect of
      adenosine analog n-phenylisopropyladenosine (PIA) on FSH-stimulated cAMP
      production was studied in staged rat seminiferous tubules. In low responsive
      stages VII-VIII of the cycle, 100 nM and 10 microM PIA inhibited FSH-stimulated
      cAMP production by 24% and 28%, respectively. To study whether PIA effect is
      mediated through Gi-protein, pertussis toxin (PT) pretreatment was used to block
      the Gi-protein. PT pretreatments of 3 or 18 h caused 42% or 16% elevation in FSH
      stimulated cAMP production, respectively. PIA blocked the stimulation caused by
      PT pretreatment. At 38 days post irradiation, when spermatocytes and round
      spermatids were decreased in number, in stages VII-VIII of the cycle the
      inhibitory effect of PIA was abolished. In high responsive stages XIV-V of the
      cycle, 100 nM PIA stimulated cAMP production by 27%, while 10 microM PIA had no
      effect. At 38 days post irradiation FSH response was decreased by 19% when
      compared to non-irradiated level, and PIA stimulated FSH-stimulated cAMP
      production by 22%. The results suggest that there are stage-specific mechanisms
      for adenosine-dependent regulation of FSH-stimulated cAMP production in the rat
      seminiferous epithelium. Advanced spermatogenic cells seem to maintain the
      mechanisms that include PIA-mediated inhibition of FSH response. Other mechanisms
      than PT-sensitive Gi-protein seem to be involved in the inhibition.

PMID- 8276130
TI  - Lactogenic hormones and extracellular matrix regulate expression of IGF-1 linked
      to MMTV-LTR in mammary epithelial cells.
AB  - The cell line MD-IGF-1, containing an ovine IGF-1 cDNA driven by the mouse
      mammary tumor virus-long terminal repeat (MMTV-LTR) promoter, was used to study
      expression of IGF-1 linked to the MMTV-LTR in bovine mammary epithelial cells in
      response to various hormonal and substratum stimuli. Acute sensitivity of the
      MMTV-LTR promoter to glucocorticoids and sex steroids was ascertained by
      transient transfection of parental MAC-T cells with an MMTV-CAT construct.
      Specifically, CAT activity was induced by glucocorticoids, but not by 17 beta
      estradiol or progesterone. Induction of MD-IGF-1 cells with dexamethasone (DEX)
      alone triggered a 29.5-fold increase in secretion of recombinant IGF-1 (348.9 vs
      11.8 pg/micrograms DNA), and stimulated a 1.7-fold increase in total DNA within
      72 h. Growth of MD-IGF-1 cells was enhanced by exogenous IGF-1, insulin, and TGF
      alpha. In contrast, TGF-beta inhibited cell proliferation, while epidermal growth
      factor, estrogen, progesterone, and testosterone had no effect. Extracellular
      matrix from the Engelbreth-Holm-Swarm (EHS) tumor, in the presence of DEX,
      prolactin (PRL), and insulin stimulated a 29.4-fold increase in secretion of IGF
      1 (591.9 pg/microgram DNA), compared with cells in absence of hormones (20.1
      pg/micrograms DNA). EHS and DEX plus PRL triggered a 63.2-fold increase in IGF-1
      secretion (689.1 pg/micrograms DNA), compared with MD-IGF-1 cells cultured on
      plastic (10.9 pg/micrograms DNA), in the absence of hormones. These data indicate
      that the MMTV-LTR is regulated by both lactogenic hormones and extracellular
      matrix in MD-IGF-1 cells and that the MMTV-LTR may be a useful regulatory element
      for targeting expression of foreign proteins in bovine mammary epithelial cells.

PMID- 8276131
TI  - Mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated decrease of the
      nuclear estrogen receptor in MCF-7 human breast cancer cells.
AB  - Treatment of MCF-7 cells with 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
      1 nM [3H]17 beta-estradiol resulted in decreased radiolabeled nuclear estrogen
      receptor (ER) levels as determined by velocity sedimentation analysis. In
      parallel studies, nuclear extracts from TCDD-treated cells also exhibited
      decreased binding to a consensus 32P-genomic estrogen responsive element (ERE) as
      determined in a gel mobility shift assay. Time-course studies showed that the
      decreases in nuclear ER and ER-ERE binding in TCDD-treated cells were observed
      within 1 to 3 h after treatment, respectively, and persisted for up to 24 h.
      Cycloheximide (10 microM) did not affect the TCDD-mediated response, whereas 1
      microM alpha-naphthoflavone, an aryl hydrocarbon (Ah) receptor antagonist,
      partially blocked downregulation of nuclear ER binding by TCDD. TCDD did not
      significantly affect steady state ER mRNA levels as determined by Northern
      analysis or the rate of ER gene transcription in a nuclear run-on assay. These
      results suggest that the TCDD-mediated decrease in nuclear ER levels is an Ah
      receptor-mediated response which occurs at the translational or post
      translational level.

PMID- 8276133
TI  - Differential regulation of the estrogen receptor mRNA by estradiol in the trout
      hypothalamus and pituitary.
AB  - In an attempt to understand the molecular mechanisms by which steroids can
      modulate brain functions in fish, we first localized the cells which produce
      estrogen receptor mRNA in the rainbow trout forebrain (Salbert et al., 1991). We
      now report how estradiol itself can alter the estrogen receptor mRNA content of
      these cells in a sterile strain of female rainbow trout. We also examined liver
      and pituitary levels of the estrogen receptor mRNA under the same estrogenic
      treatment. As revealed by slot blot and in situ hybridisations, a single
      injection (1.5 mg/kg) of estradiol can induce a strong increase (about five-fold)
      in the estrogen receptor mRNA levels in the liver, as well as a moderate increase
      (about two-fold) in two nuclei of the hypothalamus/preoptic area: the nucleus
      lateralis tuberis and the nucleus preopticus periventricularis. Conversely, no
      modifications of these levels were observed in the pars intermedia and the
      proximal pars distalis of the pituitary. Moreover, a comparison between estrogen
      receptor mRNA levels in the brain of sexually active female trout and in the
      brain of these sterile animals revealed that, in these latter, estrogen receptor
      mRNA levels are lower but can be increased by a single estradiol injection and
      reached the levels observed in mature females.

PMID- 8276132
TI  - Helix-loop-helix proteins are present and differentially expressed in different
      cell lines from the anterior pituitary.
AB  - The basic-helix-loop-helix (bHLH) class of transcriptional activators, important
      in the establishment of many different cell lineages, share two important
      properties: the ability to heterodimerize with other members of this family and
      to bind DNA containing the loose consensus sequence CANNTG. This study takes
      advantage of these shared characteristics to begin to address whether or not bHLH
      proteins are present in pituitary cells. Gel-shift and Southwestern assays using
      an oligonucleotide containing a bHLH binding consensus sequence demonstrate that
      pituitary-specific proteins are present in extracts from adult pituitary tissue
      and pituitary cell lines and bind specifically to this sequence. Pituitary
      extracts were also found to contain several factors which interact with Id
      protein, a negative regulator of bHLH activity, in Far-Western assays of protein
      protein interactions. Finally, messenger RNA for Id is present in pituitary cell
      lines but is absent in adult pituitary tissue. Together, these studies indicate
      that bHLH proteins are present in pituitary cells and their levels are
      differentially regulated in the separate cell types.

PMID- 8276134
TI  - A tetrapeptide within a receptor-binding region of human follicle-stimulating
      hormone beta-subunit, hFSH-beta-(34-37), regulates sodium-calcium exchange in
      Sertoli cells.
AB  - In a previous study, we showed that binding of FSH by cultured rat Sertoli cells
      significantly inhibited basal levels of Na+/Ca2+ exchange. Similar inhibition was
      observed when proteoliposomes enriched with bovine calf testis follicle
      stimulating hormone (FSH) receptors were stimulated with FSH. In the present
      study, we screened a series of overlapping synthetic peptide amides, representing
      the entire primary structure of the beta-subunit of hFSH, for their effects on
      sodium-dependent calcium uptake (as 45Ca2+) by monolayer cultures of Sertoli
      cells from immature rats. hFSH-beta-(33-53), previously identified as a receptor
      binding region of hFSH-beta-subunit, significantly (P < 0.05) inhibited Na+/Ca2+
      exchange. A tetrapeptide [TRDL, hFSH-beta-(34-37)] contained within this
      sequence, was observed to be equally as active as hFSH-beta-(33-53) at 200
      microM, suggesting that the regulatory effect of hFSH-beta-(33-53) on sodium
      dependent 45Ca2+ influx was due to residues 34-37. hFSH-beta-(81-95) also
      inhibited Na(+)-dependent calcium influx, although to a lesser extent than hFSH
      beta-(33-53) or hFSH-beta-(34-37). Sodium-dependent 45Ca2+ entry into Sertoli
      cells was enhanced in a concentration-related manner when extracellular sodium
      was replaced by equimolar concentrations (up to 135 mM) of choline chloride. hFSH
      beta-(34-37) significantly reduced basal uptake of 45Ca2+ in choline-containing
      buffer, but was without effect in buffer containing 135 mM NaCl.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276135
TI  - The FSH beta-subunit promoter directs the expression of Herpes simplex virus type
      1 thymidine kinase to the testis of transgenic mice.
AB  - The bovine FSH beta-subunit promoter (2.3 kb) was coupled to the coding sequence
      of the Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene and introduced
      into mouse embryos. A full-length tk transcript was found in the pituitary and
      testis. In the testis an additional truncated version of tk mRNA was also
      expressed. Two sets of primer extension fragments were identified, one
      corresponding to transcription initiation at or near the cap site of the FSH-beta
      gene, the other to transcription initiation within the tk gene. Furthermore, the
      latter, shorter transcript contained a 227 bp deletion. Only the long transcript
      was translated into immunoreactive tk in the later stages of developing
      spermatids. The tk protein was also functional in the testes, since
      spermatogenesis was either arrested or the germinal epithelium almost completely
      destroyed in transgenic males treated with the antiherpetic agent. If the FSH
      beta-HSV-tk transgene also functions correspondingly in the pituitary, these mice
      will provide a useful model for studies on FSH.

PMID- 8276136
TI  - Thyroid hormone potentiates estrogen activation of vitellogenin genes and
      autoinduction of estrogen receptor in adult Xenopus hepatocytes.
AB  - Although the important role of thyroid hormones in regulating metamorphosis of
      amphibian larvae is well known, it has not been clearly established if thyroid
      hormones have any function in the activities of adult amphibian tissues. We now
      describe a strong effect of 3,3',5-triiodothyronine (T3) on adult Xenopus liver
      cells. Low doses of T3 rapidly (within 6-12 h) potentiate the activation of
      vitellogenin (Vit) genes by estradiol-17 beta (E2) in primary cultures of adult
      male and female Xenopus hepatocytes. This effect is developmentally regulated and
      is first manifested during metamorphic climax. In an attempt to explain this
      potentiation, we find that T3 also upregulates thyroid hormone receptor beta, but
      not alpha, transcripts and rapidly enhances the autoinduction of estrogen
      receptor (ER) mRNA in adult Xenopus hepatocytes. In transient transfection of the
      Xenopus cell line XTC-2 with an estrogen response element--chloramphenicol
      transacetylase (ERE-CAT) construct T3 was found to potentiate the transcription
      by E2 from the transfected ERE, thus suggesting that it enhances the accumulation
      of functional ER. We conclude that T3 can function in adult amphibian tissues,
      and discuss the significance of thyroid hormone potentiation of responses to
      estrogen in reproductive processes.

PMID- 8276137
TI  - Effect of insulin-like growth factor-I on cholesterol side-chain cleavage
      cytochrome P450 messenger ribonucleic acid expression in ovarian theca
      interstitial cells stimulated to differentiate in vitro.
AB  - Currently available evidence supports the hypothesis that insulin-like growth
      factor-I (IGF-I) may play a role in stimulating ovarian theca-interstitial cell
      (TIC) differentiation in preantral follicles. The purpose of the present studies
      was to examine the potential role of IGF-I in TIC differentiation by determining
      the effects of IGF-I on cholesterol side-chain cleavage cytochrome P450 (P450SCC)
      mRNA expression in TIC stimulated to differentiate in vitro. TIC were isolated
      from the ovaries of hypophysectomized immature rats by Percoll gradient
      centrifugation and cultured in the presence and absence of LH and IGF-I up to 6
      days. At various times cytoplasmic RNA was extracted from the TIC and P450SCC
      mRNA was measured by specific assay using reverse transcription followed by the
      polymerase chain reaction. Increasing concentrations of LH (0-1 microgram/ml)
      stimulated a dose-related increase in P450SCC mRNA (ED50 = 36.2 +/- 5.5 ng/ml)
      which reached maximal levels at 100 ng/ml of LH. Addition of IGF-I (30 ng/ml)
      caused a small increase in P450SCC mRNA over TIC treated with LH alone but did
      not alter the ED50 for LH stimulation. IGF-I alone also stimulated an increase in
      P450SCC mRNA which reached approximately 3-fold over unstimulated levels at 100
      ng/ml. In the presence of LH, IGF-I stimulated a dose-related increase in P450SCC
      mRNA (ED50 = 1.2 +/- 0.05 ng/ml). Time-course studies revealed that expression of
      P450SCC mRNA was greatest at 2 days in TIC treated with IGF-I alone, LH alone or
      LH plus IGF-I and then declined at 4 and 6 days.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276138
TI  - Multiple changes in chromatin structure precede the transcriptional activation of
      the human growth hormone locus in placental cells.
AB  - In addition to the growth hormone gene (hGH-N) itself, the human growth hormone
      (hGH) locus contains four related genes, namely hGH-V and hCS-L, -A and -B, which
      have appeared very recently in evolution and are specifically expressed in
      placenta. With the aim of identifying the regulatory elements responsible for
      this placental-specific expression, we have mapped the DNaseI hypersensitive
      sites present at the hGH gene cluster in a placental cell line (BeWo) that
      expresses the hGH-V and hCS genes. Our results reveal a complex pattern of
      hypersensitive sites distributed along the hGH locus, most of which appear to be
      cell type-specific. Thus, we have identified placental-specific hypersensitive
      sites within the first intron of the hGH-N and hGH-V genes, but not in the
      equivalent regions of the hCS genes. In addition, we have found several placental
      specific hypersensitive sites downstream of the hCS-L and hCS-A genes, which
      might reflect the presence of enhancer elements similar to that located
      downstream of the hCS-B gene (Walker et al. (1990) J. Biol. Chem. 265, 12940).
      Comparison of BeWo cells with a placental cell line (JEG-3) which does not
      express the hGH-V and hCS genes revealed a very similar pattern of hypersensitive
      sites, suggesting that the sites detected are established before the onset of
      transcription. Our results indicate that the transition to an active hGH locus in
      placental cells requires multiple alterations in chromatin structure, and provide
      a framework for the molecular analysis of the regulatory elements and mechanisms
      mediating such processes.

PMID- 8276139
TI  - Fertilization and early development of rat oocytes induced to mature by
      forskolin.
AB  - Forskolin has been shown to successfully induce maturation of rat oocytes as
      assessed by morphological markers. The present study was designed in an attempt
      to elucidate whether oocytes, induced to mature by forskolin (10(-4) M, group A)
      in a follicle-enclosed oocyte culture, are fertilizable and can further develop
      into two-cell embryos. Oocytes exposed in vitro to either luteinizing hormone
      (LH, 5 micrograms/ml, group B) or a GnRH agonist analogue (10(-7) M, group C) as
      well as oocytes that underwent maturation in vivo (group D), served as positive
      controls. We found that similar rates of fertilization were obtained in the
      experimental and all of the above mentioned control groups (A = 78.9 +/- 4.2%, B
      = 77.9 +/- 3.1%, C = 77.5 +/- 5.5% and D = 84.7 +/- 2.7%). Cleavage rate of
      fertilized eggs from group A was significantly higher than that of eggs from
      groups B & C, and similar to that of eggs from group D (A = 63.1 +/- 6.7%, B =
      37.8 +/- 4.9%, C = 50.0 +/- 4.1%, D = 67.8 +/- 4.1%). Using functional parameters
      we hereby demonstrate that forskolin and LH are at least equally potent in
      producing fertilizable eggs that have a high potential of development into two
      cell embryos. These results further support the idea that cAMP is a mediator of
      LH action in inducing oocyte maturation.

PMID- 8276140
TI  - Tissue-specific expression of the rat androgen-binding protein/sex hormone
      binding globulin gene in transgenic mice.
AB  - The testicular Sertoli cell produces an extracellular androgen-binding protein
      (ABP) that binds testosterone and dihydrotestosterone with high affinity. The ABP
      gene also encodes plasma sex hormone-binding globulin (SHBG), which is produced
      by the liver of most species. Unlike the human, adult rats and mice do not
      express SHBG. A 5.5-kb rat genomic DNA fragment was found to contain the entire
      coding regions of ABP and 1.5 kb upstream of the transcription start site. To aid
      in identification of the promoter and enhancer regions of the ABP/SHBG gene, we
      developed transgenic mice that express the rat gene. The 5.5-kb DNA was
      microinjected into the pronuclei of fertilized mice ova, which were transferred
      to the reproductive tract of pseudopregnant females. Three of the offspring were
      identified as carriers of the rat gene by Southern hybridization and these
      founders were bred with normal mice to establish heterozygous transgenic lines.
      Northern blot analysis, RNA-PCR and sequencing of the PCR products from the adult
      transgenic mice revealed extremely high levels of the rat ABP mRNA in the testis,
      but no detectable rat ABP mRNA in liver, kidney or brain. Primer extension
      experiments showed that the correct transcript ion start site is utilized in the
      transgenes. These data demonstrate that the 5.5-kb genomic DNA fragment contains
      an element(s) capable of directing ABP gene expression in the testis. This
      enhancer should prove useful for the targeting of specific gene products to the
      mature Sertoli cell in transgenic animals.

PMID- 8276141
TI  - Functional heterogeneity of gonadotrophs in the ovine fetus: analysis by reverse
      hemolytic plaque assay.
AB  - Stimulation of sheep fetal gonadotrophs with 10(-7) M luteinizing hormone
      releasing hormone (LHRH) for 3 h in culture wells increased luteinizing hormone
      (LH) release over basal values. Using the reverse hemolytic plaque assay (RHPA),
      we demonstrated that this increase was due to a recruitment of LH-secreting
      cells. During gestation, the percentage of LH-containing cells able to release
      and the mean size of plaques were the highest at around 100-130 days and were
      usually lower in females than in males. In an attempt to delineate the
      involvement of protein kinase C (PKC) in LH release, cells were treated with an
      activator of PKC, phorbol 12-myristate 13-acetate (PMA). Stimulation of cells
      with 10(-6) M PMA for 3 h enhanced LH release in culture wells 2- to 3-fold more
      than did 10(-7) M LHRH. This increase was a consequence of an enhanced number of
      LH-secreting cells and, in males only, of an enhancement of the mean plaque size.
      The percentage of LH-secreting cells among LH-containing cells and the plaque
      areas were maximal between 110 and 120 days of gestation in both sexes. They were
      usually lower in females than in males. Stimulation of cells with LHRH plus PMA
      enhanced LH release in culture wells in an additive manner when compared to
      either factor alone in both sexes and at all fetal ages. This additive effect
      reflected an increase in the number of secreting cells. Under these conditions,
      plaque sizes were larger than the plaque sizes obtained with PMA alone in males
      and in females in late gestation. In conclusion, our results show that LHRH
      stimulated LH secretion from sheep fetal cells by recruiting secreting cells when
      compared to controls. Both 100-120 days of gestation and were higher in males
      than in females. Results following treatment of cells with PMA, either alone or
      in combination with LHRH, suggest that these two secretagogues act on two
      different subpopulations of gonadotrophs and probably through different pathways.

PMID- 8276142
TI  - Analysis of Pit-1 in regulating mouse TSH beta promoter activity in thyrotropes.
AB  - TSH beta gene expression is restricted to pituitary thyrotropes. Since Pit-1 is
      present in these cells, we characterized Pit-1 RNA and protein in thyrotropes,
      and tested its function in regulating TSH beta promoter activity. We demonstrate
      that both TtT-97 thyrotropic tumors and pituitaries contain four Pit-1
      transcripts of 3.2, 2.6, 2.4, and 1.9 kb, respectively. Only two transcripts of
      2.7 and 2.1 kb were detected in alpha TSH cells, a thyrotrope derived cell that
      no longer expresses TSH beta. Western analysis revealed Pit-1 protein in TtT-97
      cells but not in alpha TSH cells. DNase I protection assays localized Pit-1
      binding to three areas of the mouse TSH beta promoter. However, basal TSH beta
      promoter activity was minimally stimulated when alpha TSH cells or TtT-97
      thyrotropes were co-transfected with mouse Pit-1 and a mTSH beta luciferase
      construct. These studies suggest that Pit-1 is not limiting for cell-specific
      expression of the TSH beta gene in thyrotrope-derived cells and implies that
      additional thyrotropic factors are likely required.

PMID- 8276143
TI  - Effects of glucagon like peptide-1(7-36) amide on the cytoplasmic Ca(2+)
      concentration in rat islet cells.
AB  - Glucagon like peptide-1(7-36) amide (GLP-1(7-36)amide) stimulates both insulin
      secretion and the efflux of 45Ca2+ from 45Ca(2+)-preloaded rat islets in a Na(+)
      dependent manner. This indicates that the peptide stimulates insulin secretion by
      Na(+)-dependently increasing the intracellular concentration of Ca2+ ([Ca2+]IC).
      However, whether GLP-1(7-36)amide actually affects the [Ca2+]IC in islet cells is
      not known. We therefore preloaded rat islet cells with the Ca(2+)-fluorophor fura
      2-AM and examined the [Ca2+]IC in spectrophotofluorometry. We found that GLP-1(7
      36)amide increased [Ca2+]IC both at 3.3 and 8.3 mM glucose but only in a medium
      containing both Ca2+ and Na+. Also the adenylate cyclase activator, forskolin
      (2.5 microM), increased the [Ca2+]IC but this action was evidenced also in the
      absence of extracellular Na+. Furthermore, the Ca(2+)-channel inhibitor, D-600
      (50 microM), prevented the rise in [Ca2+]IC after both forskolin and GLP-1(7
      36)amide, whereas pertussis toxin had no effect. The results show that GLP-1(7
      36)amide increases the [Ca2+]IC in islets cells by an action that most likely is
      due to uptake of extracellular Ca2+ by a Na(+)-dependent mechanism, whereas
      forskolin increases [Ca2+]IC independently on Na+. It is hypothesized that GLP
      1(7-36)amide stimulates a Na(+)-dependent step prior to the catalytic unit of the
      adenylate cyclase complex in islet cells.

PMID- 8276144
TI  - Rat prolactin-like protein A partial gene and promoter structure: promoter
      activity in placental and pituitary cells.
AB  - Rat prolactin-like protein A (rPLP-A) is a member of a rapidly expanding family
      of prolactin-related proteins that are expressed during pregnancy by the rat
      placenta according to specific developmental patterns. Although the factors
      involved in the pituitary-specific expression of the prolactin and growth hormone
      genes themselves have been extensively studied, essentially nothing is known of
      the factors responsible for the placental expression of these new family members.
      In this paper we describe the isolation of rPLP-A genomic clones, analyze a
      portion of the 5' flanking sequence of this gene and use the recently described
      rat choriocarcinoma cell line, Rcho, in transient transfection studies to show
      that a 975 base-pair (bp) fragment of 5' flanking sequence is sufficient to
      specify placental expression of the rPLP-A gene.

PMID- 8276145
TI  - Transcriptional regulation of human corticotropin releasing factor gene
      expression by cyclic adenosine 3',5'-monophosphate: differential effects at
      proximal and distal promoter elements.
AB  - cAMP participates in the regulation of endogenous hypothalamic and placental CRF
      by increasing levels of both peptide secretion and mRNA expression. In previous
      studies we have shown that stimulation of the protein kinase A-dependent pathway
      by cAMP analogues or forskolin produced a dose-dependent increase in levels of
      CRF mRNA when the intact hCRF gene was stably transfected and expressed in the
      mouse corticotroph AtT20 cell line. In the present study, we explored the
      mechanism of the cAMP-dependent increase in CRF gene expression in the stably
      transfected AtT20 cell line using pharmacologic, slot-blot, and RNase mapping
      methodologies. Following incubation with cAMP, there was a rapid increase in CRF
      mRNA which was completely blocked by pre-treatment with actinomycin D, an
      inhibitor of transcription. Cycloheximide, an inhibitor of protein synthesis,
      produced an independent increase in CRF mRNA, but did not change the relative
      induction of CRF mRNA produced by cAMP. Solution hybridization studies using
      intron- and exon-specific hCRF probes demonstrated a rapid rise in nuclear CRF
      hnRNA, which was apparent within 15 min of cAMP incubation and preceded the rise
      in cytoplasmic CRF mRNA. RNase mapping studies demonstrated that CRF
      transcription was initiated at discrete promoter sites in CRF-AtT20 cells, and
      that this pattern of promoter utilization was similar to that observed in mRNA
      derived from sites of endogenous CRF expression, human placenta and human
      hepatoma NPLC cell line. Treatment with cAMP selectively increased CRF mRNA
      transcripts initiated at the proximal promoter site, but had little or no effect
      on transcripts initiated at the distal promoters. We conclude that cAMP effects
      on CRF gene expression occur rapidly, do not require new protein synthesis, and
      are initiated within the nuclear compartment, consistent with a direct effect on
      CRF gene transcription. This effect is mediated predominantly through the
      proximal promoter element, while more distal promoters are less sensitive to
      transcriptional activation by cAMP.

PMID- 8276146
TI  - [Role of the creatine phosphokinase system in skeletal muscles during adaptation
      of the body to prolonged physical exertion].

PMID- 8276147
TI  - [Age-related features of dopaminergic regulation of thyrotropic hormone secretion
      in boys and youths aged 3 to 15 years and in adult men].

PMID- 8276148
TI  - [Specific spatial relationship of pathologic EEG activity in patients with
      temporal lobe epilepsy].

PMID- 8276149
TI  - [Comparative analysis of optimal regimes of muscular work after adaptation to
      cold and physical exertion].

PMID- 8276150
TI  - [Various reactions to thermal exposure in people with varying levels of thermal
      resistance].

PMID- 8276151
TI  - [Analysis of the work efficiency of a preventive institution using automated
      means of prenosologic diagnosis].

PMID- 8276152
TI  - [Adaptation to hypocaloric diet in obese patients].

PMID- 8276153
TI  - [Functional correlation in chewing musculature and shape change of the human
      lower mandible during osteogenesis].

PMID- 8276154
TI  - [Fibrinolytic and thrombolytic properties of a low-molecular weight heparin
      nicotinamide complex].

PMID- 8276155
TI  - [Physiologic basis for prevention of early aging in man].

PMID- 8276156
TI  - [Response of the human cardiovascular system to dosed exercise depending on the
      type of circulatory self-regulation].

PMID- 8276157
TI  - [Age-related features of hypoxia compensation by means of increased dissociation
      of oxyhemoglobin].

PMID- 8276158
TI  - [Functional asymmetry of the brain and its role in the pathogenesis of arterial
      hypertension].

PMID- 8276159
TI  - [Changes in the success of purposeful human activity in motivationally determined
      states as affected by pain of threshold intensity].

PMID- 8276160
TI  - [Rotatory nystagmus in different variations of afferent pathway interaction].

PMID- 8276161
TI  - [Changes in optical tracking function in opium addicts].

PMID- 8276162
TI  - [Information approach to the analysis of age-related dynamics of EEG in 7-18 year
      old boys and youths during solution of mental arithmetic problems].

PMID- 8276163
TI  - [Symmetric approach to rheovasogram analysis].

PMID- 8276164
TI  - [Individual differences in changes in cardiac rhythmograms after reporting the
      result of activity].

PMID- 8276165
TI  - [Analysis of various qualitative effects associated with forced expiration].

PMID- 8276166
TI  - [Trace processes in memory and body pattern].

PMID- 8276167
TI  - [Influence of interaction between feet and support on tonic activity of leg
      muscles during standing].

PMID- 8276168
TI  - [Functional properties of the neuromuscular system in athletes of various
      specialties].

PMID- 8276169
TI  - Abstracts of selected papers presented at the 34th annual meeting of The Japanese
      Society of Gastroenterology. Utsunomiya, Japan, October 12-14, 1992.

PMID- 8276170
TI  - Application of the crypt-isolation technique to flow-cytometric analysis of DNA
      content in colorectal neoplasms.
AB  - BACKGROUND/AIMS: Conventional flow-cytometric analysis of colorectal tumor DNA
      content includes both tumor and stromal cell DNA. To improve the method, we
      evaluated the DNA content of purified epithelial cells using the crypt-isolation
      technique. METHODS: Normal and neoplastic crypts were isolated from fresh
      resected colorectum nonenzymatically. Isolated crypts were digested into single
      nuclei suspensions and examined by flow cytometry (FCM). Internal controls from
      normal crypts were used to define diploidy. The neoplastic nuclei in the same
      individual and mixtures of both normal and neoplastic nuclei in various ratios
      were analyzed. RESULTS: Tumors having both diploid and aneuploid stemlines were
      found more frequently than that reported using conventional FCM. Near-diploid DNA
      stemlines with DNA indices ranging between 0.90 and 1.10 were detectable. The
      cases of advanced cancer in which the DNA index was between 0.90 and 0.95 were
      associated significantly with Dukes' stage C. CONCLUSIONS: This is the first
      reported analysis of the DNA content of "pure" neoplastic colorectal epithelia
      using FCM. Multiploid and near-diploid stemlines were more accurately analyzed
      than that using conventional FCM.

PMID- 8276171
TI  - Esophageal clearance function following treatment of esophagitis.
AB  - BACKGROUND/AIMS: To investigate whether healing of the esophagitis was associated
      with an improvement in esophageal clearance function, 15 patients with endoscopic
      and histologically confirmed erosive esophagitis were studied both before and
      after 1-month treatment with 40 mg/day of omeprazole. METHODS: All patients were
      studied before and after treatment by perfusion manometry to measure esophageal
      pressures, and a traction measuring device was used to record aboral forces
      generated by graded intraluminal distension. RESULTS: Before treatment, standard
      manometry showed reduced lower esophageal sphincter pressures (4 mm Hg [range, 2
      9] vs. a control of 12 mm Hg [range, 5-25]; P < 0.01) and distal peristaltic
      amplitudes (29 mm Hg [range, 5-57] vs. a control of 55 mg Hg [range, 32-90]; P <
      0.01). Responses to distension were also abnormal with a higher threshold for
      induction of contractile activity (12 mL [range, 8.5-14] vs. control values of 5
      mL [range, 3-10]; P < 0.01) and weaker clearance forces (5 g [range, 0-80] vs.
      control values of 20 g [range, 8-90]; P < 0.01). After treatment, all patients
      showed endoscopic and histological evidence of healing, but not consistent
      improvement in either lower esophageal sphincter pressure (5 mm Hg [range, 3-7];
      P > 0.05 vs. pretreatment) or peristaltic amplitude (35 mm Hg [range, 10-55]) was
      found. However, responses to distension did improve, with a decrease in
      distension threshold to 10 mL (range, 7-14; P = 0.04) and enhancement of traction
      force to 14 g (range, 0-95; P < 0.01). Patients with the worst pretreatment
      distension responses showed the least improvement with therapy. CONCLUSIONS:
      Improvement in esophageal clearance can be achieved by the healing of
      esophagitis, although the capacity for functional benefit appears to be related
      to the degree of dysfunction present before therapy.

PMID- 8276172
TI  - Peanut lectin stimulates proliferation in colonic explants from patients with
      inflammatory bowel disease and colon polyps.
AB  - BACKGROUND/AIMS: The TF antigen (galactose-beta 1,3-N-acetylgalactosamine alpha)
      is overexpressed in malignant and premalignant colonic epithelium. Previous
      studies have shown that peanut lectin (PNA), which binds TF, is mitogenic for
      normal human colonic epithelium. This study aimed to determine its effect on
      abnormal colonic epithelium. METHODS: Crypt cell proliferation rate (CCPR) was
      measured using vincristine arrest and mucus synthesis by incorporation of
      radiolabeled N-acetyl glucosamine in colonoscopic biopsy specimens cultured with
      and without PNA. RESULTS: Unstimulated CCPR was greater in patients with
      ulcerative colitis than in patients with histologically normal colon. PNA (25
      micrograms/mL) produced a 25% average increase in CCPR in tissues from patients
      with ulcerative colitis, Crohn's disease, and colonic polyps. In ulcerative
      colitic biopsy specimens incubated with PNA, CCPR increased to more than double
      that of unstimulated normal colonic epithelium. In controls, the response to PNA
      was greater when adjacent specimens were positive for PNA (avidin-biotin)
      histochemistry than when they were negative. Mucus synthesis was increased by an
      average 75% over 24 hours by PNA. CONCLUSIONS: Increased TF expression by
      premalignant epithelia may allow stimulation of proliferation by dietary
      galactose N-acetylgalactosamine-binding lectins. If the hyperplasia-dysplasia
      cancer hypothesis is correct, this could explain the increased colon cancer risk
      in ulcerative colitis.

PMID- 8276173
TI  - Na+ transport in human proximal colonic apical membrane vesicles.
AB  - BACKGROUND/AIMS: The mechanisms of Na+ movement across colonocyte plasma
      membranes in the human colon are not well understood. Current studies were
      undertaken to investigate Na+ transport pathways in apical membranes of proximal
      organ donor colons. METHODS: Purified apical membrane vesicles and rapid
      filtration 22Na-uptake techniques were used. RESULTS: An outwardly directed H(+)
      gradient (pH 5.5 in/7.5 out) increased 22Na uptake into these vesicles. H+
      gradient-driven 22Na uptake was significantly reduced by voltage clamping with
      K+/valinomycin, but was significantly stimulated by creation of an inside
      negative potential. Potential sensitive 22Na uptake was inhibited by Na+ channel
      inhibitors phenamil and benzamil. Electroneutral 22Na uptake was insensitive to
      phenamil and benzamil, but was inhibited by amiloride, 5-(N,N-dimethyl)amiloride,
      5-(N,N-hexamethylene)amiloride, and 5-(N-ethyl-N-isopropyl)amiloride.
      Electroneutral 22Na uptake showed saturation kinetics with an apparent Michaelis
      constant for Na+ of 11.8 +/- 2.4 mmol/L and a maximal velocity of 2.5 +/- 0.6
      nmol.mg protein-1 x 5 s-1. The mechanism of amiloride inhibition was
      noncompetitive with an inhibitor constant for amiloride of 325 mumol/L.
      Acetazolamide, furosemide, bumetanide, 4-acetamido-4'-isothiocyano-2,2'
      disulfonic acid stibene, and 4,4'-di-isothiocyanatostilbene-2,2'-disulfonic acid
      (1 mmol/L each) failed to inhibit 22Na uptake. Li+ and NH4+ (but not Cs+, K+, or
      choline+) inhibited H(+)-gradient driven 22Na uptake. CONCLUSIONS: Na+ transport
      in human proximal colonic apical membrane vesicles involves both conductive Na+
      transport and an electroneutral Na(+)-H+ exchange.

PMID- 8276174
TI  - Gastroesophageal reflux during gastrostomy feeding.
AB  - BACKGROUND/AIMS: Aspiration pneumonia is one of the most serious complications of
      gastrostomy tube feeding, with a reported incidence of 10%-20% in nursing home
      patients. The aims of this prospective study were to examine lower esophageal
      sphincter (LES) pressure before and after placement of gastrostomy tubes and to
      examine the effects of rapid intragastric bolus and slow, continuous feeding on
      LES pressure. METHODS: Ten subjects were enrolled in the study. Basal LES
      pressure was measured before and after placement of gastrostomy tubes.
      Thereafter, LES pressure was measured for 15 minutes during rapid intragastric
      infusion of 250 mL of an enteral feeding formula and 100 mL water and continuous
      infusion of the enteral feeding formula at 80 mL/h. Scintigrams evaluating
      gastroesophageal reflux were obtained during each method of feeding. RESULTS:
      Placement of gastrostomy tubes had no effect on basal LES pressure. Rapid
      intragastric bolus infusion led to a reduction in LES pressure to incompetent
      levels at 2.1 +/- 2.0 mm Hg (P < 0.001). Free gastroesophageal reflux to the
      sternal notch was shown by scintigraphy. Slow, continuous gastrostomy feedings
      did not alter LES pressure (P > 0.05) or show free gastroesophageal reflux by
      scintigraphy. CONCLUSIONS: Gastroesophageal reflux and aspiration in patients fed
      via the gastrostomy tube may be caused by LES relaxation secondary to gastric
      distention caused by distention of the stomach.

PMID- 8276175
TI  - Kinetics of hepatic bile acid handling in cholestatic liver disease: effect of
      ursodeoxycholic acid.
AB  - BACKGROUND/AIMS: Ursodeoxycholic acid (UDCA) is clinically beneficial in chronic
      cholestatic liver disease, but the underlying mechanisms are unclear. It has been
      suggested that intrahepatic retention of endogenous hydrophobic bile acids
      contributes to cholestasis and that the hydrophilic bile acid UDCA reduces this
      retention; the aim of our study was to test these hypotheses. METHODS: Twelve
      patients with primary biliary cirrhosis (PBC) and 5 with primary sclerosing
      cholangitis (PSC) were studied before and during UDCA (10 mg.kg-1.day-1) and
      compared with 11 healthy controls. Following intravenous 75Se labeled homocholic
      acid taurine (75SeHCAT) in the fasting state, abdominal gamma camera imaging was
      performed for 90 minutes. Initial hepatic uptake, transit time, net, and absolute
      excretory rates for 75SeHCAT were measured. RESULTS: Mean initial hepatic uptake
      was not different between patients and controls (17.2% and 19.9% dose/minute, not
      significant). However, net and absolute excretory rates were significantly
      reduced in patients (1.4% vs. 3.7% dose/minute, P < 0.0001; and 2.35% vs. 3.96%
      dose/minute, P < 0.02, respectively), and hepatic transit time was prolonged
      (18.7 minutes vs. 11.6 minutes, P < 0.002). UDCA improved net and absolute
      hepatic excretory rates and transit time (1.43% to 1.96% dose/minute, P < 0.001;
      2.35% to 3.15% dose/minute, P < 0.005 and 18.7 to 14.7 minutes, P < 0.001,
      respectively). However, UDCA did not alter initial hepatic uptake. CONCLUSIONS:
      In PBC and PSC, there is a defect in hepatic bile acid excretion but not in
      uptake, implying bile acid retention. This retention is reduced by UDCA.

PMID- 8276177
TI  - Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon.
AB  - BACKGROUND/AIMS: Polyunsaturated soybean lecithin (55%-60% phosphatidylcholine
      [PC]) protects against fibrosis in alcohol-fed baboons. The present study was
      undertaken to determine whether PC is the active agent. METHODS: Virtually pure
      PC (equivalent to that contained in the lecithin) was administered for up to 6.5
      years with or without alcohol, and the results were compared with those of
      unsupplemented groups. RESULTS: Control livers remained normal, whereas 10 of 12
      baboons fed alcohol without PC developed septal fibrosis or cirrhosis with
      transformation of 81% +/- 3% of the hepatic lipocytes to collagen-producing
      transitional cells. By contrast, none of the eight animals fed alcohol with PC
      developed septal fibrosis or cirrhosis, and only 48% +/- 9% of their lipocytes
      were transformed, indicating that PC was indeed the protective compound. Ethanol
      feeding also resulted in decreased liver phospholipids and PC, and both were
      corrected by the supplementation. Furthermore, PC stimulated collagenase activity
      in cultured lipocytes. This PC consisted of several species, mainly
      dilinoleoylphosphatidylcholine (40%-52%) and palmitoyl
      linoleoylphosphatidylcholine (23%-24%). Only dilinoleoylphosphatidylcholine
      duplicated the effect of the PC on collagenase. Other species of PC,
      phosphatidylethanolamine, free fatty acids, or choline were without effect.
      CONCLUSIONS: PC prevents alcohol-induced fibrosis and cirrhosis in nonhuman
      primates, and dilinoleoylphosphatidylcholine appears to be the active species,
      possibly by promoting collagen breakdown.

PMID- 8276176
TI  - Prevention of ischemia/reperfusion injury in the rat liver by atrial natriuretic
      peptide.
AB  - BACKGROUND/AIMS: Atrial natriuretic peptide (ANP) protects against
      hypoxia/reoxygenation-induced damage of cultured hepatocytes, thus suggesting a
      therapeutic potential in the liver. Therefore, the effects of ANP on hepatic
      ischemia/reperfusion injury after warm ischemia were studied. METHODS: Livers of
      male Sprague-Dawley rats subjected to 60 minutes of warm ischemia at 37 degrees C
      were perfused in the presence or absence of 200 and 20 nmol/L ANP. RESULTS:
      Sinusoidal lactate dehydrogenase efflux increased to 2000 +/- 264 and 126 +/- 50
      mU.min-1.g liver-1 after 1 minute and 60 minutes of reperfusion, but it only
      increased to 1240 +/- 160 and 22 +/- 16 mU.min-1.g liver-1 in the presence of 200
      nmol/L ANP during the preischemic and postischemic perfusion period. The
      postischemic bile flow (0.67 +/- 0.18 microL.min-1.g liver-1) was significantly
      improved with 200 nmol/L ANP (0.92 +/- 0.05) and showed a linear correlation to
      biliary glutathione excretion. In contrast, 20 nmol/L ANP had no protective
      effects. Administration of 200 nmol/L ANP during the preischemic perfusion period
      alone (but not after starting reperfusion) markedly preserved postischemic liver
      function. CONCLUSIONS: Continuous ANP administration or ANP pretreatment alone
      prevents hepatic ischemia/reperfusion injury, possibly because of influences on
      intracellular signal transduction processes. The correlation between bile flow
      and biliary glutathione excretion supports the hypothesis that biliary
      glutathione transport is one of the osmotic driving forces in postischemic bile
      formation.

PMID- 8276178
TI  - HLA DR4 is a marker for rapid disease progression in primary sclerosing
      cholangitis.
AB  - BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is an inflammatory disease
      of the biliary tree associated with an increase in the HLA alleles DR3, DR52a,
      DR2, Dw2, and a decrease in DR4. However, it is not certain which of these
      alleles provides the primary associations. Our aim was to establish the primary
      HLA associations with PSC and to assess the ability of HLA alleles to mark for
      disease progression. METHODS: By applying molecular techniques to archival
      tissue, we have genotyped 83 PSC patients from two populations and 131 controls
      for the alleles HLA DR2, DR3, DR4, DRw12, DR52a, and Dw2. RESULTS: HLA DR3,
      DR52a, DR2, and Dw2 were all significantly increased in PSC, with the relative
      risk for DR52a and Dw2 being greater than for DR3 and DR2, respectively. HLA DR4
      was significantly decreased, but this may be artifactual to the DR3, DR2
      increase. HLA DR4 and not DR52a marks for rapid disease progression in both our
      PSC populations. CONCLUSIONS: HLA DR52a and Dw2 are the best candidate alleles
      for providing the known HLA association with PSC. HLA DR4 and not DR52a marks for
      rapid disease progression in our two PSC populations.

PMID- 8276179
TI  - Inhibition of nonlysosomal calcium-dependent proteolysis by glycine during anoxic
      injury of rat hepatocytes.
AB  - BACKGROUND/AIMS: The mechanism by which glycine protects against hepatocyte death
      during anoxia remains unclear. Nonlysosomal proteolysis, including calpain
      proteolysis, has been implicated as a mechanism of lethal cell injury. However,
      the effect of glycine on nonlysosomal proteolysis is unknown. The aim of this
      study was to ascertain if glycine cytoprotection is associated with inhibition of
      nonlysosomal proteolysis. METHODS: Rat hepatocyte suspensions were rendered
      anoxic using an anaerobic chamber. Cell viability was measured by propidium
      iodide fluorometry. Nonlysosomal protease activity was quantitated by the release
      of trichloroacetic acid-soluble free amines or tyrosine. Calpain protease
      activity was measured using a fluorogenic substrate. RESULTS: Glycine and alanine
      (but not valine) markedly improved cell viability during anoxia in a
      concentration-dependent manner. During anoxia, the majority of nonlysosomal
      proteolysis (60%) was dependent on extracellular Ca2+. Glycine only inhibited
      that portion of nonlysosomal proteolysis that was dependent on extracellular
      Ca2+. Amino acids inhibited the anoxia-stimulated increase in calpain protease
      activity with the same specificity and concentration-dependence observed for
      cytoprotection. Glycine was more potent in directly inhibiting purified m-calpain
      as compared with mu-calpain protease activity. CONCLUSIONS: Glycine may exert its
      cytoprotective activity during lethal anoxic hepatocyte injury, in part by
      inhibiting Ca(2+)-dependent degradative, nonlysosomal proteases, including
      calpains.

PMID- 8276180
TI  - Induction of heat-shock gene expression in postischemic pig liver depends on
      superoxide generation.
AB  - BACKGROUND/AIMS: Both hemorrhagic and cardiogenic shock are associated with
      hepatic shock gene expression at resuscitation. This study investigated the
      potential role of intravascular superoxide anion as a proximal trigger of heat
      shock protein gene expression. METHODS: Preanesthetized pigs were subjected to
      120 m of total warm hepatic ischemia. The survival model consisted of warm, total
      hepatic ischemia and reperfusion (with active portal-systemic bypass) followed by
      reperfusion and survival for 3 days. Serial hepatic biopsy samples were evaluated
      for the expression of heat shock protein 72 (HSP-72) messenger RNA (mRNA) by
      Northern and Western analysis and by in situ RNA hybridization. The possible role
      of intravascular O2- as a mediator of heat shock response was evaluated by its
      specific inhibition by the intravenous infusion of recombinant human superoxide
      dismutase (SOD). RESULTS: Ischemia for 120 minutes followed by 60 minutes of
      reperfusion caused accumulation of HSP-72 mRNA. Transcripts were localized to
      hepatocytes. HSP-72 mRNA was detected neither following ischemia alone nor when
      SOD was infused for 15 minutes at reperfusion. Three days later, transcripts were
      not detectable, but HSP-72 protein accumulated irrespective of SOD
      administration. CONCLUSIONS: Warm hepatic ischemia induces the hepatocyte
      expression of HSP-72 at reperfusion by a mechanism that is dependent upon the
      superoxide anion, probably generated intravascularly. However, the transient
      dismutation of superoxide is insufficient to suppress subsequent accumulation of
      HSP-72.

PMID- 8276181
TI  - Increased fibronectin-receptor expression in colon carcinoma-derived HT 29 cells
      decreases tumorigenicity in nude mice.
AB  - BACKGROUND/AIMS: Following malignant transformation, epithelial cells of
      colorectal carcinomas, unlike normal colonic epithelial cells, no longer express
      the alpha 5 beta 1 fibronectin receptor. We hypothesized that the loss of alpha 5
      beta 1 expression might facilitate the tumorigenicity of transformed colonic
      cells. METHODS: To examine this hypothesis, we established subclones of the human
      colon adenocarcinoma cell line HT 29, which differ in their fibronectin receptor
      expression and tested their tumorigenicity in nude mice. RESULTS: Our data
      indicate that the capacity to form tumors in nude mice after subcutaneous
      injection was significantly lower for alpha 5-positive than for alpha 5-negative
      cell clones. In addition, tumors from clones expressing no detectable levels of
      alpha 5 beta 1 grew rapidly, whereas tumors expressing elevated levels of
      fibronectin receptor grew slowly. Despite similar rates of adhesion to
      fibronectin for alpha 5-positive and alpha 5-negative cell clones in vitro,
      deposition of fibronectin in tumor-surrounding stroma was increased in tumors
      derived from alpha 5-positive cells. CONCLUSIONS: Our results indicate that an
      increase of the alpha 5 beta 1-mediated interaction of malignant cells with the
      extracellular matrix may be responsible for decreased tumorigenicity of malignant
      transformed cells in colorectal carcinomas.

PMID- 8276182
TI  - Autoantibodies against integral membrane proteins of the nuclear envelope in
      patients with primary biliary cirrhosis.
AB  - BACKGROUND/AIMS: Autoantibodies against nuclear membrane proteins have been
      identified in patients with primary biliary cirrhosis (PBC). The aim of the
      present study was to determine the incidence of these autoantibodies in patients
      with PBC and examine their significance. METHODS: An assay using recombinant
      polypeptides was designed to unequivocally detect autoantibodies against gp210
      and the lamin B receptor, integral proteins of the nuclear membranes. RESULTS:
      Autoantibodies against gp210 were detected in 15 of 159 patients with PBC and 0
      of 46 controls. Autoantibodies against lamin B receptor were detected in 2
      patients with PBC and 0 controls. The presence of these autoantibodies had a
      sensitivity of 11% and specificity of 100% for the diagnosis of PBC.
      Autoantibodies against gp210 were present in 4 of 19 (21%) patients with PBC who
      did not have detectable antimitochondrial antibodies. Patients with PBC and gp210
      autoantibodies had a higher incidence of associated arthritis. CONCLUSIONS:
      Autoantibodies against gp210 and the lamin B receptor are present in
      approximately 10% of patients with PBC. These autoantibodies are highly specific
      for the diagnosis of PBC and may be useful in diagnosing individuals without
      antimitochondrial antibodies and in identifying a subgroup of patients with an
      increased incidence of associated arthritis.

PMID- 8276183
TI  - Intravenous contrast medium accentuates the severity of acute necrotizing
      pancreatitis in the rat.
AB  - BACKGROUND/AIMS: Contrast-enhanced computed tomography (CECT) is used to show
      areas of decreased pancreatic perfusion in severe acute pancreatitis (AP). To
      evaluate possible adverse effects of the contrast medium (CM) on the course of
      AP, the impact of intravenous CM in AP of graded severity in the rat was studied.
      METHODS: Pancreatitis of three levels of severity was induced in Sprague-Dawley
      rats with intravenous cerulein hyperstimulation plus time- and pressure
      controlled intraductal infusion of saline or glycodeoxycholic acid. At 7 hours,
      control and pancreatitis animals received intravenous ionic CM, nonionic CM, or
      saline. The principal outcome measures were 24-hour survival, trypsinogen
      activation peptides (TAP) in ascites, and histological acinar necrosis score.
      RESULTS: There was no measurable effect of CM on the index features in control
      animals or animals with mild or moderate AP. In severe AP, CM caused a
      significant increase in mortality, ascites TAP, and necrosis score. CONCLUSIONS:
      Intravenous CM increases pancreatic injury when administered early in the course
      of severe experimental AP. Because CM may convert borderline ischemia to
      irreversible necrosis, CECT performed early in pancreatitis to show poor
      perfusion and predict areas of necrosis may depict a self-fulfilling prophecy.
      Early CECT should be reconsidered and perhaps avoided.

PMID- 8276184
TI  - Pathogenic factors in early recurrence of cholesterol gallstones.
AB  - BACKGROUND/AIMS: Supersaturation of bile with cholesterol, rapid nucleation of
      cholesterol crystals, and/or incomplete emptying of the gallbladder are believed
      to be required for gallstone formation. The importance of these factors for the
      recurrence of gallbladder stones was studied. METHODS: Twenty patients, untreated
      after successful shock wave therapy, were studied in a matched case-control
      design for bile acid turnover, composition of duodenal bile, and gallbladder
      emptying. In 10 of them, gallstones had recurred within 12 +/- 2 months (X +/-
      SEM); the other 10 had been free of stones since 22 +/- 3 months. RESULTS: In
      each group, duodenal bile was supersaturated with cholesterol in 8 of 10 patients
      and showed abnormal nucleation time of cholesterol crystals in half of the
      patients. Patients with recurrent stones had smaller pool sizes of cholic acid (
      43%) and enhanced conversion of cholic acid to deoxycholic acid. The odds for
      stone recurrence were ninefold increased in the presence of excessive deoxycholic
      acid (exceeding cholic acid) in the bile acid pool or incomplete emptying of the
      gallbladder (residual volume > 5 mL) in response to cholecystokinin. The odds
      ratio was over 20-fold increased when incomplete emptying of the gallbladder
      coincided with supersaturated bile or with excessive deoxycholic acid.
      CONCLUSIONS: Enhanced conversion of cholic acid to deoxycholic acid and
      incomplete emptying of the gallbladder could be important cofactors for the
      recurrence of gallstones.

PMID- 8276185
TI  - Gallstone recurrence after shock-wave therapy.
AB  - BACKGROUND/AIMS: The long-term outcome of nonoperative gallstone therapy depends
      on both absence of stones and absence of biliary pain. The aim of the present
      study was to determine the rate of stone recurrence and the rate of symptoms
      within 5 years after successful shock wave lithotripsy combined with bile acid
      therapy. METHODS: One hundred consecutive patients (single stones, n = 89; 2 or 3
      stones, n = 11) were followed up for a median of 4.3 years after stone
      disappearance and discontinuation of bile acids. RESULTS: Twenty-three of the 100
      patients developed recurrent stones. Calculated by actuarial analysis, the
      recurrence rate was 7% +/- 3%, 11% +/- 3%, 13% +/- 4%, 20% +/- 5%, and 31% +/- 7%
      (mean +/- SD) at 1, 2, 3, 4, and 5 years, respectively. The recurrent stones were
      small (6 +/- 5 mm) and were associated with recurrent biliary pain in 14 (61%) of
      the 23 patients. Repeated shock wave lithotripsy and/or bile acid medication
      resulted in stone disappearance in only 10 of 20 patients with recurrence.
      CONCLUSIONS: The long-term rate of stone recurrence after lithotripsy of
      primarily solitary gallbladder calculi is lower than expected from post-bile acid
      dissolution trials. Recurrence of stones frequently is associated with recurrence
      of biliary pain.

PMID- 8276186
TI  - Identification of human biliary alpha 1-acid glycoprotein as a cholesterol
      crystallization promoter.
AB  - BACKGROUND/AIMS: We have recently outlined the biochemical features of a human 42
      kilodalton biliary glycoprotein that shows concentration-dependent cholesterol
      crystallization-promoting activity. The goal in this work was to establish its
      identity and to examine some aspects of its biochemical properties relative to
      its activity. METHODS: Internal amino acid sequencing following tryptic digestion
      was performed. Based upon this result, immunoreactivity against the 42-kilodalton
      glycoprotein was examined using a relevant antibody. With the same antibody, the
      42-kilodalton glycoprotein was isolated from bile and assayed for activity.
      Sequential enzymatic deglycosylation of successive terminal glycans of the
      purified glycoprotein was performed, and the effects on both reductions in
      molecular radius (M(r)) and on comparative promoter activities were examined.
      RESULTS: Both amino acid sequence and immunochemical data identify the 42
      kilodalton glycoprotein as a biliary form of alpha 1-acid glycoprotein. When
      purified by immunoaffinity chromatography, potent promoting activity shown was
      proportionately reduced by successive removal of terminal glycans that also
      reduced the M(r)s. CONCLUSIONS: The 42-kilodalton cholesterol crystallization
      promoting glycoprotein is now identified as a biliary form of alpha 1-acid
      glycoprotein. Further, some aspects of the important role of glycans in this
      extensively glycosylated protein have been explored.

PMID- 8276187
TI  - Albumin messenger RNA as a marker of circulating hepatocytes in hepatocellular
      carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is one of the most frequent
      malignancies. Liver transplantation is theoretically the treatment of choice
      because it eliminates both the hepatocellular carcinoma and the cirrhosis. High
      frequency of relapse observed after liver transplantation may be explained by the
      existence of undetectable metastasis before transplantation. The aim of this
      study was to determine whether albumin messenger RNA (mRNA), a specifically
      hepatocyte-expressed gene, could be a marker of metastasis in hepatocellular
      carcinoma. METHODS: Albumin mRNA from circulating malignant hepatocytes was
      detected in the blood by reverse transcription followed by enzymatic
      amplification. RESULTS: Albumin mRNA was found in the blood of 3 patients with
      histologically proven metastatic hepatocellular carcinoma and in 9 of 21 patients
      with hepatocellular carcinoma and undetectable metastases, giving a percentage
      rate of 43, similar to the relapse rate following liver transplantation for
      hepatocellular carcinoma. None of the 8 patients with secondary liver cancer had
      detectable albumin mRNA. CONCLUSIONS: These results suggest that patients with
      hepatocellular carcinoma and no detectable albumin mRNA in the blood may be a
      subgroup with a low risk of relapse following liver transplantation.

PMID- 8276188
TI  - The development of a mutation in the precore region of the hepatitis B virus in a
      chronically infected individual.
AB  - Over a 15-year period, a white American woman was observed to have progressive
      hepatitis B that underwent hepatitis Be antigen (HBeAg) positivity to anti-HBe
      positivity with development of cirrhosis. This patient was found to have a non
      sense mutation in the second codon of the pre-C region of the hepatitis B virus
      genome after her anti-HBe seroconversion but not in her serum when she was
      HBeAg+. As controls, serial blood specimens were analyzed from 12 other American
      patients who spontaneously converted from HBeAg to anti-HBe, who underwent an
      interferon alfa-associated HBeAg to anti-HBe seroconversion, and who did not
      seroconvert with interferon alfa therapy. No mutations in the pre-C region were
      observed to arise in these individuals. In conclusion, non-sense mutations that
      occur in the pre-C region in locations other than the 28th codon can be
      associated with HBeAg negative progressive liver disease. This report of a non
      sense mutation occurring over time is unusual in that it occurred in a white
      American patient.

PMID- 8276189
TI  - Cholestatic hepatitis leading to hepatic failure in a patient with organ
      transmitted hepatitis C virus infection.
AB  - A 51-year-old heart transplant recipient who developed subfulminant hepatic
      failure because of organ-transmitted hepatitis C virus (HCV) infection is
      described. He presented with a predominantly cholestatic liver damage after heart
      transplantation. An extensive evaluation, including abdominal ultrasound and
      computed tomography scan and endoscopic retrograde cholangiopancreatography was
      unrevealing. Liver biopsy, however, was suggestive of a large duct obstruction
      with prominent portal and pericellular fibrosis, marked cholestasis,
      pericholangitis with marked ductular proliferation, and diffuse hepatocyte
      degeneration. Antibody to HCV (anti-HCV) was initially negative. He deteriorated
      in the ensuing 3 months. A repeat enzyme immunoassay-2 test for anti-HCV 4 months
      after initial presentation was weakly positive. Quantitation of serum HCV RNA by
      branched DNA assay revealed high level viremia, 547 x 10(6) genome equivalents
      per milliliter. Using in situ polymerase chain reaction, HCV RNA was detected in
      the cytoplasm in > 80% of the hepatocytes. The patient underwent interferon alfa
      therapy, and serum HCV RNA levels were reduced 20-fold after four doses.
      Unfortunately, the patient developed pulmonary aspergillosis and died. This case
      illustrates that in immunosuppressed patients anti-HCV is not a good marker for
      the diagnosis of HCV infection, and HCV can cause a progressive form of
      cholestatic liver disease mimicking a large duct obstruction.

PMID- 8276190
TI  - Cryptosporidiosis: the complexity of intestinal pathophysiology.

PMID- 8276191
TI  - Adherent bacteria: breaching the mucosal barrier?

PMID- 8276192
TI  - Prevention of alcohol-induced hepatic fibrosis by phosphatidylcholine.

PMID- 8276193
TI  - Contrast-enhanced computed tomography in acute pancreatitis: is it beneficial or
      harmful?

PMID- 8276194
TI  - Recurrence of gallstones following nonsurgical therapy with extracorporeal shock
      wave lithotripsy.

PMID- 8276195
TI  - An assay for micrometastatic hepatocellular carcinoma.

PMID- 8276196
TI  - The pathogenesis of gallstone-induced pancreatitis.

PMID- 8276197
TI  - Maximal bile acid biosynthesis in humans.

PMID- 8276198
TI  - Is Barrett's guilty as charged?

PMID- 8276199
TI  - Cancer surveillance in Barrett's esophagus: what is the end point?

PMID- 8276200
TI  - Fecal occult blood testing will fail to detect colonic polyps.

PMID- 8276201
TI  - Detection of colorectal adenomas by fecal occult blood tests.

PMID- 8276202
TI  - Enterotoxic effect of stool supernatant of Cryptosporidium-infected calves on
      human jejunum.
AB  - BACKGROUND/AIMS: The clinical pattern of cryptosporidial diarrhea suggests an
      enterotoxic mechanism. No evidence for this mechanism has been reported thus far.
      This study aimed to look for enterotoxic effect elaborated by Cryptosporidium.
      METHODS: The effects on human intestinal transport of stool supernatant of
      diarrheal calves infected with Cryptosporidium parvum were examined. Aliquots of
      centrifuged and filtered stools were added to the mucosal or serosal side of
      human jejunum obtained from patients undergoing surgery and mounted in Ussing
      chambers. Electrical parameters were recorded. Stool supernatants of uninfected
      calves served as a control. RESULTS: The mucosal addition of 2.5 mg protein of
      fecal supernatant from diarrheal calves induced a prompt and significant increase
      in short circuit current with no effects on tissue conductance. The serosal
      addition of this material and the addition of control supernatant to either side
      did not induce modifications of electrical parameters. The enterotoxic effect was
      dose-dependent and saturable. It was reversible by withdrawing the supernatant
      from the incubation medium. The electrical effect was chloride- and calcium
      dependent and was sensitive to heating. CONCLUSIONS: An enterotoxic activity is
      present in the stools of Cryptosporidium-infected calves. This activity may be
      responsible for secretory diarrhea in humans.

PMID- 8276203
TI  - Serum hyaluronan and changes in sinusoidal perfusion.

PMID- 8276204
TI  - Hypercoagulability in inflammatory bowel disease.

PMID- 8276205
TI  - Occult enteric infection by Ancylostoma caninum: a previously unrecognized
      zoonosis.
AB  - BACKGROUND/AIMS: Human disease caused by the canine hookworm Ancylostoma caninum
      and a high incidence of eosinophilic enteritis have been reported from northern
      Queensland, Australia. The aim of this study was to evaluate patients with
      unexplained abdominal pain and a possible association with cryptic infections by
      A. caninum. METHODS: The clinical and demographic features of patients from this
      region with eosinophilic enteritis (group A1, n = 42), obscure abdominal pain
      associated with (group A2, n = 105) and without (group A3, n = 84) blood
      eosinophilia were reviewed and sera were tested against A. caninum excretory
      secretory antigens by enzyme-linked immunosorbent assay (ELISA) and Western blot.
      Four additional patients, two with confirmed A. caninum, had hookworm infection.
      RESULTS: The level of dog ownership in these four groups was 79%-100%, higher
      than in the local population (P < 0.001). The ELISA tested positive in 71% of A1,
      67% of A2, and 30% of A3, versus 8% in controls (P < 0.002). All cases tested
      were positive on Western blot versus 10% of controls (P < 0.0001). The ELISA
      values increased with chronicity and decreased during convalescence. CONCLUSIONS:
      We conclude occult human A. caninum infections are common and are characterized
      by eosinophilic enteritis and obscure abdominal pain with or without blood
      eosinophilia. The diagnosis can be confirmed by serology.

PMID- 8276206
TI  - The effect of dexamethasone administration on rat intestinal permeability: the
      role of bacterial adherence.
AB  - BACKGROUND/AIMS: Previous studies have shown that dexamethasone administration to
      rats results in diminution of biliary secretory immunoglobulin A concentration
      and alters intestinal barrier function to bacteria. The aims of this study were
      to examine and characterize the effect of dexamethasone on intestinal
      permeability and to determine the possible influence of bacterial adherence to
      the mucosa in this process. METHODS: Groups of adult Fisher rats were studied,
      and the effects of dexamethasone administration and bowel decontamination on
      bacterial adherence and intestinal permeability were determined in various bowel
      segments. RESULTS: Dexamethasone administration was associated with a significant
      increase in bacterial adherence to the mucosa, which was most pronounced in the
      cecum (4.33 +/- 0.2 colony forming units (cfu) (log10) per gram of mucosa for
      control vs. 6.23 +/- 0.2 for dexamethasone). This was accompanied by significant
      alterations in intestinal permeability as measured by a decrease in
      transepithelial electrical resistance (49.5 +/- 4.1 omega.cm2 for control vs.
      25.4 +/- 2.5 omega.cm2 for dexamethasone). Dual sodium-mannitol flux analysis
      showed this defect to be predominantly paracellular. Antibiotic decontamination
      of the intestine completely abrogated the intestinal permeability defect observed
      in this model. CONCLUSIONS: Bacterial-mucosal cell interactions may be
      responsible for alterations in intestinal permeability after dexamethasone
      administration.

PMID- 8276207
TI  - Association of p53 mutations with short survival in colorectal cancer.
AB  - BACKGROUND/AIMS: Mutations in p53, a tumor suppressor gene located on chromosome
      17p, are the most frequent genetic alterations found in human cancers. Increased
      intracellular concentration of p53, which is frequently but not systematically
      related to p53 mutation, has been proposed to be associated with poor prognosis
      in some tumor types. In colorectal cancer, this significance is still a matter of
      debate. To directly investigate the relationship between prognosis and p53
      mutation, this study screened a series of 85 colorectal carcinomas for mutations
      in exons 5-8 of this gene. METHODS: Polymerase chain reaction-amplified products
      from tumor DNA were analyzed by denaturing gradient gel electrophoresis and
      direct DNA sequencing. RESULTS: Forty-four tumors were found to be mutated (52%).
      A strong correlation between the presence of a mutation and short survival was
      observed (P = 0.003). When tumors were classified according to their histological
      stage, a multivariate Cox model analysis showed that p53 mutation, rather than
      17p allelic loss (previously proposed to convey prognostic information), was
      retained as the only independent prognostic factor (relative risk, 2.25; 95%
      confidence interval, 1.06-4.80; P < 0.029). CONCLUSIONS: Combined with staging,
      direct monitoring of p53 mutation improves prognostic accuracy for colorectal
      cancer.

PMID- 8276208
TI  - Response of rat immature enterocytes to insulin: regulation by receptor binding
      and endoluminal polyamine uptake.
AB  - BACKGROUND/AIMS: The mechanism(s) by which insulin stimulates enzyme expression
      in rat immature enterocytes are unknown. The purpose of this study was to
      investigate these mechanism(s). METHODS: The effects of insulin or an
      antireceptor monoclonal antibody (RPN 538) were assessed on microvillous enzyme
      activities and the endoluminal uptake of [14C]spermine. Changes in de novo
      synthesis of polyamines were measured by mucosal ornithine decarboxylase
      activity. RESULTS: In sucklings (day 14), administration of insulin failed to
      induce intestinal ornithine decarboxylase activity, whereas in older rats (day 18
      and 20), ornithine decarboxylase was enhanced by 2-2.5-fold. Immature enterocytes
      from sucklings, pretreated with alpha-difluoromethylornithine, remained sensitive
      to insulin and expressed enzyme activities at levels equal to controls. In
      response to insulin, the uptake of [14C]spermine and the mucosal concentrations
      of spermine and spermidine were increased by 30%, 13%, and 39%, respectively.
      Administration of RPN 538 had no effect on [14C]-spermine uptake, but it
      prevented the effects of endogenous insulin on enzyme expression. CONCLUSIONS:
      The enzymatic response of immature enterocytes to insulin is mediated by binding
      of the hormone to its receptor and is transduced into the cell without de novo
      synthesis of polyamines. The regulation by insulin of the endoluminal uptake of
      spermine could be critical for intestinal maturation.

PMID- 8276209
TI  - Do continuous infusions of omeprazole and ranitidine retain their effect with
      prolonged dosing?
AB  - BACKGROUND/AIMS: Prolonged infusions of H2-antagonists are commonly used in
      intensive care units, although little is known about their antisecretory efficacy
      beyond the initial 24 hours of dosing. The aim of this study was to assess the
      antisecretory effects of infusions of ranitidine and omeprazole for a period of
      72 hours. METHODS: Twelve healthy volunteers received individually titrated 72
      hour intravenous infusions of omeprazole, ranitidine, or placebo in a double
      blind, crossover study. Gastric pH and dosing requirements were compared.
      RESULTS: The median percentage of time with pH > 4 (interquartile range) was 93%
      (88%-95%) on day 1 and 96% (94%-99%) on day 3 with omeprazole and 67% (56%-78%)
      and 43% (31%-51%), respectively, with ranitidine (both P < 0.001 vs. omeprazole).
      The mean doses (+/- SD) required on days 1 and 3 for omeprazole were 235.8 +/- 44
      mg and 134.0 +/- 37 mg (P < 0.0001), and ranitidine doses were 502.5 +/- 76 mg
      and 541.8 +/- 25 mg, respectively (P = 0.05). CONCLUSIONS: Omeprazole infusions
      consistently maintained gastric pH above 4 over a period of 72 hours with
      progressively lower doses. Significant tolerance to the antisecretory effect of
      ranitidine infusion developed in 72 hours, which was not overcome despite
      individually titrated doses of more than 500 mg/24 hours. Consequently,
      application of pharmacodynamic results of single-day H2-blocker and proton-pump
      inhibitor studies to prolonged infusion trials for stress ulcer-related bleeding
      is inappropriate.

PMID- 8276210
TI  - Saccharomyces boulardii inhibits secretagogue-mediated adenosine 3',5'-cyclic
      monophosphate induction in intestinal cells.
AB  - BACKGROUND/AIMS: The yeast Saccharomyces boulardii inhibits the secretion induced
      by cholera toxin (CT) in rat jejunum. The present study was aimed at unraveling
      the mechanism by which S. boulardii protects intestinal cells against CT.
      METHODS: CT-induced adenosine 3',5'-cyclic monophosphate (cAMP) levels were
      measured by radioimmunoassay in intestinal epithelial cells IEC-6 or HT29-D4
      cells exposed to whole yeast or to culture medium conditioned by S. boulardii (Sb
      conditioned medium). RESULTS: Sb-conditioned medium significantly reduced CT
      induced cAMP levels in IEC-6 cells. This effect was eliminated by heat treatment,
      trypsin hydrolysis, and trichloroacetic acid precipitation of Sb-conditioned
      medium. When conditioned medium was fractionated on polyacrylamide gel under
      nondenaturing conditions, neutralizing activity was shown to be associated with a
      120-kilodalton protein. The neutralizing activity was not attributable to
      proteolytic activity against CT. Sb-conditioned medium reduced the amount of cAMP
      induced by CT as well as Escherichia coli thermolabile toxin or forskolin in HT29
      D4 cells. The modulation of secretagogue-induced cAMP by Sb-conditioned medium
      did not occur in the presence of pertussis toxin. CONCLUSIONS: These results
      suggest that the neutralization of CT by S. boulardii is mediated by a specific
      yeast protein and involves a receptor that is negatively coupled to adenylate
      cyclase.

PMID- 8276211
TI  - Exposure of the rat small intestine to raw kidney beans results in reorganization
      of absorptive cell microvilli.
AB  - BACKGROUND/AIMS: A single exposure to raw kidney beans (RKB) results in
      vesiculation, shortening, and then regrowth of microvilli in the rat small
      intestine. This study investigated changes that occur in the structure of
      microvilli 2-10 hours after RKB exposure. METHODS: Circumferences of microvilli
      from absorptive cells obtained sequentially after challenge with RKB or chow were
      assigned to one of three groups: small, intermediate, or large. The distribution
      and concentration of actin in intact mucosae or isolated epithelial sheets were
      determined by confocal laser scanning microscopy, immunocytochemistry, and
      immunoblot analysis with specific probes. RESULTS: Six hours after exposure to
      RKB, most microvilli were large, abnormal in shape, and contained significantly
      more actin filaments than large microvilli from control rats. In addition, the
      fluorescence intensity of F-actin increased within injured microvilli without
      changes in the total intracellular actin concentration. By 8-10 hours after
      challenge with RKB, some microvilli remained larger than those of control rats
      but had resumed their normal shape and contained fewer actin filaments than at 6
      hours. CONCLUSIONS: Exposure of the rat small intestine to RKB results in
      enlargement of absorptive cell microvilli and reorganization of membrane and core
      actin filaments without changes in intracellular actin concentration. Enlarged
      microvilli are rapidly repaired.

PMID- 8276212
TI  - Proliferative responses of HT29 and Caco2 human colorectal cancer cells to a
      panel of lectins.
AB  - BACKGROUND/AIMS: Altered lectin binding is common in malignant and premalignant
      epithelia, but its functional significance is unclear. This study examined the
      proliferative effects of four lectins on HT29 and Caco2 colon cancer cells.
      METHODS: Proliferation was assessed in log growth and confluent culture by
      thymidine incorporation and cell counts. Peanut agglutinin (PNA) binding was
      characterized by Scatchard analysis and electrophoresis of lectin affinity
      purified cell surface-radiolabeled preparations. RESULTS: PNA, 5 micrograms/mL,
      increased thymidine incorporation in HT29 but had no effect on Caco2. Wheat germ
      agglutinin and concanavalin A stimulated proliferation slightly at 0.5-1.0
      microgram/mL but were inhibitory at higher concentrations. Ulex europaeus 1 had
      no significant effect. Similar results were obtained when proliferation was
      assessed by cell counts and with confluent cell cultures. Scatchard analysis with
      both cell lines showed multisite best fit models with similar binding affinities.
      Three PNA-binding glycoproteins were identified in both cell lines, but two were
      of lower molecular weight in HT29 than in Caco2. Membrane preparations from a
      resected colorectal cancer contained a 30-kilodalton PNA-binding glycoprotein
      similar to that in HT29 cells. CONCLUSIONS: Lectins are plentiful in the normal
      diet and often escape digestion. This study suggests that altered expression of
      lectin receptors, particularly the upregulation of PNA receptor seen in colonic
      malignancy and hyperplasia, may have an important role in growth modulation.

PMID- 8276213
TI  - Effects of dietary menhaden oil on mucosal adaptation after small bowel resection
      in rats.
AB  - BACKGROUND/AIMS: Adaptive hyperplasia of the small intestine is important in the
      outcome of short bowel syndrome. Previous studies have shown that long-chain fats
      stimulate this process. In the present study, the trophic effects of dietary
      menhaden oil, a highly unsaturated fat source, on mucosal adaptation following
      small bowel resection in rats was evaluated. METHODS: Thirty weanling Sprague
      Dawley rats and their controls were fed diets containing fats provided primarily
      as menhaden oil, safflower oil, or beef tallow. After 4 weeks, animals underwent
      a 70% jejunoileal resection. Mucosal mass, DNA, protein, and sucrase levels were
      assessed 14 days after a 70% jejunoileal resection or control feeding. Serum
      fatty acid composition and several gastrointestinal hormone levels were measured.
      RESULTS: Resected animals fed menhaden oil showed a marked increase in mucosal
      weight, DNA, and protein levels compared with rats fed the other fat sources.
      Enteroglucagon level was increased in all resected groups, but least increased in
      the menhaden-fed animals. In contrast, peptide YY concentrations were most
      increased in animals fed menhaden oil. CONCLUSIONS: Menhaden oil appears more
      effective in inducing intestinal adaptation than less highly unsaturated fats.
      Analysis of gastrointestinal hormones revealed no clear-cut explanation for this
      finding, other than a modest but associated increase in peptide YY levels.

PMID- 8276214
TI  - [Comparative redundancy of genes of various organisms and viruses].
AB  - This paper is devoted to the comparative study of redundancy of genetic texts of
      various organisms and viruses. To determine the redundance of a gene, we have
      introduced the strict measure for that latter. The measure for a text's
      redundance is the length of restriction of Frequency/Correlation Dictionary of a
      given genetic text. Frequency/Correlation Dictionary is the ser of all
      subsequences belong to a given genetic text, accompanied by the frequencies of
      their occurrence. The restriction length is defined as that one, for which all
      the subsequences (of that length) are unique. We have found, that genes of human
      viruses are less redundant, in comparison to those of human genes. Other aspects
      of a comparative redundance investigations of the genes are discussed. The
      problem of the determination of "truet" intron could be treated by this
      methodology, as well, as the evolution of genome.

PMID- 8276215
TI  - [Esterase-6 activity in Drosophila melanogaster strains with varying male mating
      activity].
AB  - Analysis of the stocks of Drosophila melanogaster and of interstock hybrids with
      different male reproductive activity revealed positive connection between this
      index and the activity of esterase-6 in the reproductive system: ejaculatory
      duct, paragonies and ejaculatory bulb. X-chromosomes and chromosome 3 participate
      in genetic control of interstock differences of both sexual and esterase-6
      activity.

PMID- 8276216
TI  - [Construction of a mapping panel of human-rodent hybrid cells].
AB  - A clone panel of 27 human-Chinese hamster and 4 human-mouse somatic cell hybrids
      which contained as minimum five discriminating clones for any chromosome pairs
      was set up. Segregation analysis of 45 human chromosome-specific isoenzymes and
      PCR markers in hybrid clones allowed to demonstrate a possibility to apply the
      obtained panel for chromosome mapping of human genes.

PMID- 8276217
TI  - [Region of the prune locus in Drosophila melanogaster is transcriptionally
      saturated].
AB  - Using Northern analysis three transcription areas are detected in the gene prune
      region from which three different mRNAs 1.8, 1.75 and 1.0 kb in length
      transcribe. Corresponded cDNAs are cloned. Only 1.8 kb mRNA is shown to be
      changed in size and quantity in the case of the pn1 and pn3 mutations. This mRNA
      seems to be a gene prune transcript. From the analysis of the portion of cDNA
      c1.1 nucleotide sequence corresponded 1.75 kb mRNA follows that its putative
      amino acid product contains a heme-binding site which is characterized for P450
      cytochrome superfamily. On the basis of presented results and published data by
      Teng et al [1] it may be concluded that at least five different mRNAs transcribe
      in the gene prune region in area spanning about 10 kb.

PMID- 8276218
TI  - [Mechanism of chromosome loss after irradiation of mature Drosophila sperm].
AB  - The frequency of radiation-induced chromosome losses is not connected with
      heterochromatic content but depends on the total chromosomal DNA content. This
      dependence is of the selective nature and appears as a result of the effect of
      dominant lethality of non-repaired euchromatic breaks. Simultaneous losses of the
      two chromosomes in one nucleus are not independent, because of the interaction of
      the heterochromatic breaks underlying these losses. The conclusion is made that
      the chromosome losses are involved in the exchange events accompanied by the
      centromere deletion.

PMID- 8276219
TI  - [Genetic analysis of the resting EEG parameters of schizophrenics and their
      relatives].
AB  - The heritability of the resting EEG parameters was studied in 45 schizophrenic
      families. In offspring--parent pairs (N = 94) and sibs pairs (N = 27) high
      correlation of average power values of frequency bands between relatives was
      found (r > 0.5 for alpha and beta power; r 0.2 to 0.45 for delta and theta power
      in different electrode placement). Linear discriminate functions (LDF) to
      separate 1) a control group (N = 20) from healthy relatives (N = 46), 2) control
      group from relatives with borderline pathology (N = 36) and 3) healthy relatives
      from relatives with borderline pathology were obtained. True classification is
      possible in 79%, 81% and 76% cases, heritability coefficients of LDF are 47.7,
      64.6 and 57.1% respectively.

PMID- 8276220
TI  - [Relationship between chromosomal Q-polymorphism and variability of
      morphophysiologic characters in man].
AB  - To analyse ontogenic and adaptive significance of the chromosomal Q-polymorphism,
      the relationship between individual heterozygosity for 12 chromosomal Q
      polymorphic bands and variability of 2 anthropometric (weight and stature) and 2
      physiological (systolic and diastolic blood pressure) adaptively important traits
      have been studied in two ethnically different populations, living in different
      ecological conditions. For most of the studied traits, nonsignificant
      relationships between chromosomal Q-polymorphic band heterozygosity and
      morphophysiological variables have been found. Similar results have been obtained
      for correlations between the mean number of Q-bands on genome and variability of
      quantitative traits. These results suggest that the chromosomal Q-polymorphism is
      selectively neutral in human postnatal ontogenesis.

PMID- 8276221
TI  - [Polymorphism of C-heterochromatin chromosome regions in the etiology of human
      aneuploidy].
AB  - Cytogenetic study of the C-heterochromatic polymorphisms in 202 individuals from
      the Down's syndrome families and in 31 control individuals was undertaken. In 58
      families the source of an additional chromosome was taken into account. It was
      shown that in the donors of extra chromosome, due to nondisjunction in the Ist
      meiotic division, the frequency of heteromorphism was higher (0.61) than in other
      groups: donors with the 2nd meiotic nondisjunction (0.44), partners of donors
      (0.48) and controls (0.46). Also, increase in heteromorphism rate was found in a
      group of young mothers (0.56) compared with a group of old mothers (0.45). The
      role of heterochromatic regions in chromosome nondisjunction is discussed from
      the point of view of meiotic nonhomologues coordination.

PMID- 8276222
TI  - [Planning of sampling for linkage analysis. Sample size and sampling method].
AB  - There is a proposed method for evaluation of the minimal sample size needed for
      the predefined quality of the linkage decision. It is applied to samples of
      arbitrary structured pedigrees ascertained via proband in accordance with
      different ascertainment schemes. The quality of the linkage decision is
      determined by the I and II type errors of the likelihood ratio constructed with a
      simple alternative hypothesis about the recombination fraction value. Comparison
      of these minimal sample sizes for different ascertainment schemes leads to a
      possibility to choose the best of them when the model of genetic control of two
      traits is given. A possibility to evaluate each of these ascertainments by a cost
      of the sample collection and to point out the cheapest is considered.

PMID- 8276223
TI  - [Heterogeneous selection in a subdivided population with unstable deme sizes].
AB  - The influence of small deme sizes oscillations in a one-locus two-allele model is
      considered. The dependence of frequency deviations from the fluctuation numbers
      is obtained. The new method of selection coefficients and migration matrix
      estimation from the deme numbers and the allele frequencies observations is
      found.

PMID- 8276224
TI  - [Mapping of cloned fragments of the macrophage-stimulating factor receptor gene
      (FMS) from a non-amplified library of human leukocyte genes].
AB  - For investigation of FMS gene polymorphism and mutations that reveal functionally
      meaning in leukemia and myelodysplastic disorders the overlapping recombinants
      lambda-clones inserted by FMS gene fragments have been obtained from human
      leukocyte genomic library in the EMBL 3A phage by using oligonucleotide prode (27
      nucleotides) based on 12 exon of the FMS gene. 15 DNA probes were prepared by
      subcloning the lambda-clones obtained in the pBSKS+ plasmid. The probes obtained
      allow to analyse extracellular, transmembrane and tyrosine kinase regions of the
      FMS gene independently.

PMID- 8276225
TI  - [Empirical estimation of recurrence risk in diseases with variable age-at-onset:
      correction].
AB  - Combinatorial approach in empirical estimation of recurrence risks in variable
      age-at-onset (AO) was elaborated in [2], where special combinatorial coefficient
      was introduced, the so called "constrained polynomial coefficient", which permit
      to count the permutations of AO-sibling classes, constrained by their age to the
      time of study (ATS). Unfortunately giving account of method of calculation md-
      the table morbidity rate--for siblings of age d in [2] were not introduced
      limitations for AO or ATS of those siblings, which were affected before or not
      yet reached the age d under evaluation. Lack of the limitations result in the
      estimate of prevalence (i.e. the proportion of affected siblings, with the given
      AO, among all the siblings), but not incidence or age-specific morbidity rate
      (i.e. the proportion of the siblings, affected in the d-th age interval among
      those siblings, who reached and/or outlive the age d, being free of disease
      before the age d under evaluation). In this communication the oversight is
      removed and the method of calculation of md is simplified: only the two classes
      instead of a lot of the possible AO-classes of siblings are considered, namely-
      "affected in the d-th age interval" and "health in the d-th age interval" under
      evaluation. Thus, the way of calculation of md may be reduced to the simple
      binomial case.

PMID- 8276226
TI  - [Transcription of the prune gene during a position effect of the mosaic type in
      Drosophila melanogaster].
AB  - Analysis of transcription of the gene prune being undergone position effect
      variegation in the inversion In(1LR)pn2a is presented. Using Northern
      hydridization with following densitometric analysis of blots it was shown that
      the quantity of the prune mRNA is decreased 1.8 +/- 0.4 times in comparison with
      normal. Transcripts differing from wild type sizes are not detected. On the basis
      of the results obtained of inactivation propagation in the case of the position
      effect.

PMID- 8276227
TI  - [Cloning of the Bacillus subtilis chromosome fragment suppressing the Escherichia
      coli sbc B mutation].
AB  - A. 3.54 kb chromosomal fragment of Bacillus subtilis was cloned on the plasmid
      pBluescript SK(+). The fragment suppresses the repair deficiency of the sbc B15
      mutation of Escherichia coli. It is shown that the B. subtilis gene of
      exonuclease! is expressed in the E. coli cells.

PMID- 8276228
TI  - Linkage disequilibrium in the white locus region of Drosophila melanogaster.
AB  - Linkage disequilibrium between molecular polymorphisms in a 10 kb region in the
      white locus of Drosophila melanogaster, revealed with a battery of four-cutter
      restriction enzymes, was investigated in 266 lines sampled from seven natural
      populations around the world. A total of 73 (35 restriction site, 37
      insertion/deletion and 1 inversion) polymorphisms were detected, of which 55 non
      unique polymorphisms were analysed for linkage disequilibrium. Clustering of
      significant linkage disequilibrium was observed in the transcriptional unit of
      the white locus as in Miyashita & Langley (1988). It was shown that about two
      thirds of the 2-locus combinations showing significant linkage disequilibrium
      have similar degree and direction of association over different populations.
      Despite lower divergence in allelic frequencies of molecular polymorphisms among
      populations, an increase in the proportion of 2-locus pairs showing significant
      linkage disequilibrium is observed in the transcriptional unit. Large values of
      Ohta's D measure ratio (1982a, b) cluster in the transcriptional unit, and
      correspond to significant linkage disequilibria. Although the exact molecular
      mechanism is not clear, these results suggest that epistatic selection is
      responsible for significant linkage disequilibrium in the transcriptional unit of
      this locus.

PMID- 8276229
TI  - Mutability, sterility and suppression in P-M hybrid dysgenesis: the influence of
      P subline, cross, chromosome, sex and P-element structure.
AB  - Three Harwich P sublines with different P-element activity potential were used to
      investigate the influence of P-derived chromosomes on snw mutability and vg
      suppression and to relate the induction of these dysgenic traits to the number
      and structure of P elements. Destabilization of the snw allele, a measure of P
      transposase activity, was differentially influenced by the major autosomes.
      Chromosome 2 of the standard Harwich subline, Hw, induced only 60% of the level
      of mutability relative to chromosome 3, whereas chromosome 3 of the weakest
      Harwich subline, Hf, induced only 50% of the mutability relative to chromosome 2.
      In somatic suppression of the vg21-3 allele, chromosome 3 of the Hf subline
      produced a lower level of complete suppression as compared to chromosome 3 of the
      Hw or the Hs subline (the high hybrid-dysgenesis-inducing subline). The level of
      these dysgenic traits and GD sterility, was not correlated with the number of P
      elements per individual (67-68) or per chromosome arm which was very similar
      among the sublines. The number of complete P elements per genome, based on
      Southern blot analysis of the X and major autosomes, ranged from 15 to 19.
      Destabilization of the snw allele and vg suppression by chromosome 3 was
      correlated with a greater number of complete P elements. Two novel unexpected
      observations emerged from these studies: both snw mutability and vg suppression
      data demonstrated high P-element activity in hybrids derived from non-dysgenic
      crosses irrespective of Harwich subline, indicating a lack of P-cytotype
      regulation. Mutability in non-dysgenic males ranged from 40 to 60% of the level
      found in dysgenic males. The high snw mutability and low GD sterility in non
      dysgenic hybrids suggests that these traits may arise by a different mechanism.

PMID- 8276230
TI  - The use of retrotransposons as markers for mapping genes responsible for fitness
      differences between related Drosophila melanogaster strains.
AB  - Hitch-hiking of dispersed mobile elements serving as molecular markers was used
      as a new tool for mapping quantitative trait loci in Drosophila melanogaster. Two
      Drosophila strains with high fitness (HA) were backcrossed repeatedly to a
      closely related strain with low fitness (LA) to initiate experimental populations
      with expected HA gene frequencies of 1/32. The frequencies of 19 insertion sites
      of the retrotransposons mdg1 and copia were analyzed after 11 to 17 generations.
      Frequencies of sites from the HA line increased substantially in the
      pericentromeric region, indicating that one or more loci responsible for the
      fitness difference between the strains were located there. A maximum likelihood
      (ML) procedure was applied to estimate selection coefficients associated with the
      markers, and this indicated a broad, strongly selected region of the chromosome.
      At least one additional locus was localized in the middle of the 2L arm. Possible
      applications of this method are discussed.

PMID- 8276231
TI  - The mouse t complex distorter-3 (Tcd-3) locus and transmission ratio distortion.
AB  - A novel central partial t haplotype was generated by screening for a
      recombination event between overlapping distal and proximal partial haplotypes.
      This haplotype contains just two elements--Tcrt and Tcd-3t--involved in the t
      specific transmission ratio distortion phenotype. Breeding analysis of males that
      carry this chromosome provides evidence that Tcd-3 is, indeed, a distorter locus
      and not a second responder. Furthermore, the data indicate that a single well
      defined distorter locus is insufficient to overcome completely the self
      destructive, low transmission ratio distortion phenotype expressed by the t
      allele at the t complex responder locus, although a small, but highly
      significant, effect was observed.

PMID- 8276232
TI  - Parental imprinting on the mouse X chromosome: effects on the early development
      of X0, XXY and XXX embryos.
AB  - To examine the effects of X-chromosome imprinting during early mouse
      embryogenesis, we attempted to produce XM0, XP0, XMXMY, XMXPY and XMXMXP (where
      XM and XP stand for the maternally and the paternally derived X chromosome,
      respectively) making use of mouse strains bearing the translocation Rb(X.2)2Ad
      and the inversion In(X)1H. Unlike XMXPY embryos, XMXMY and XMXMXP conceptuses
      suffered from severe growth retardation or abnormal development characterized by
      deficient extra-embryonic structures at 6.5-7.5 days post coitum (dpc). A
      cytogenetic study suggested that two XM chromosomes remaining active in certain
      nonepiblast cells were responsible for the serious developmental abnormality
      found in these embryos disomic for XM. Although matings involving females
      heterozygous for Rb(X.2)Ad hinted at the paucity of XP0 embryos relative to those
      having the complementary karyotype of XMXMXP, further study of embryos from
      matings between females heterozygous for In(X)1H and Rb2Ad males did not
      substantiate this observation. Thus, the extensive peri-implantation loss of XP0
      embryos shown by Hunt (1991) may be confined to X0 mothers. Taken together, this
      study failed to reveal a parentally imprinted X-linked gene essential for early
      mouse embryogenesis other than the one most probably corresponding to the X
      chromosome inactivation centre.

PMID- 8276233
TI  - Spacing and orientation of bipartite DNA-binding motifs as potential functional
      determinants for POU domain factors.
AB  - Investigation of the large POU domain family of developmental regulators has
      revealed a molecular mechanism by which highly related transcription factors
      sharing common DNA-binding motifs act to functionally discriminate their cognate
      DNA sequences. Studies of two classes of neuron-specific POU domain factors (III
      and IV) indicate that functional specificity on their native response elements is
      achieved by accommodating different nucleotide spacing between variably oriented
      bipartite core DNA-binding motifs. The preferred orientation of the POU-specific
      domain of the neuronal factors on their native response elements appears to be
      opposite that of Pit-1 and Oct-1. Members of POU-III (Brn-2) class exhibit
      remarkable flexibility in DNA site recognition (tolerating core motifs spaced by
      0, 2, or 3 nucleotides), whereas POU-IV (Brn-3) class is highly constrained
      (tolerating core motifs with a spacing of 3 nucleotides). The molecular
      determinant of the constraint in DNA site selection appears to be imparted by 3
      amino acid residues in the amino-terminal basic region in concert, with helix 2
      of the POU homeo domain which together are involved in minor groove and possibly
      phosphate backbone contacts. Similar mechanisms may underlie differential
      flexibility in spacing and orientation for diverse families of transcription
      factors.

PMID- 8276234
TI  - DNA bending and orientation-dependent function of YY1 in the c-fos promoter.
AB  - The assembly of multicomponent complexes at promoters, enhancers, and silencers
      likely entails perturbations in the path of the DNA helix. We present evidence
      that YY1, a ubiquitously expressed DNA-binding protein, regulates the activity of
      the c-fos promoter primarily through an effect on DNA structure. YY1 binds to and
      induces a phased DNA bend at three sites in this promoter. By use of a truncated
      c-fos promoter activity containing a single functional YY1 site, we show that YY1
      represses promoter activity but that repression does not appear to be an
      intrinsic property of the protein in this context. Moreover, when the orientation
      of the YY1 site is reversed, YY1 activates the same promoter. Repression by YY1
      is also alleviated by changing the relative phasing of factor-binding sites on
      either side of YY1. We conclude that the principal function of YY1 in this
      promoter is to bend DNA to regulate contact between other proteins. Thus, YY1
      represents a new class of transcription factors that influences promoter function
      by affecting promoter structure rather than by directly contacting the
      transcriptional machinery. We provide evidence that the product of the male sex
      determination gene SRY may also belong to this class of structural factors.

PMID- 8276235
TI  - Site-specific HU binding in the Mu transpososome: conversion of a sequence
      independent DNA-binding protein into a chemical nuclease.
AB  - HU is a small, basic, sequence-independent DNA-binding protein capable of
      engineering DNA deformations required for the formation of higher order
      nucleoprotein structures. One such complex is the Mu Type 1 transpososome, where
      the ends of Mu are stably synapsed by a tetramer of Mu A and cleaved at their 3'
      ends. HU is believed to play a critical role in transpososome assembly, which
      requires the communication of the two Mu ends and the transpositional enhancer.
      Although footprinting studies have clearly defined the DNA regions bound by Mu A,
      no protection could be ascribed to the HU protein by DNAse I, MPE.Fe(II) or
      hydroxyl radical methods (Lavoie et al. 1991). To directly probe HU interactions
      with the transpososome DNA, we have coupled HU to a DNA cleavage reagent, iron
      EDTA, and report here the first HU "footprint". HU-nuclease cleavage was
      detectable at specific sites within an 83-bp spacer DNA separating the left-end
      most L1 site from its neighboring L2 site. This HU binding was specific since it
      could not be competed with 10-fold excess supercoiled DNA. We postulate that HU
      promotes the formation of a tight DNA bend or loop in this region which
      facilitates the communication of Mu A monomers during complex assembly. This
      method may prove generally useful for the localization of sequence-independent
      DNA-binding proteins on DNA and within higher oder nucleoprotein structures.

PMID- 8276236
TI  - Double-strand signal sequence breaks in V(D)J recombination are blunt, 5'
      phosphorylated, RAG-dependent, and cell cycle regulated.
AB  - Immunoglobulin and T-cell receptor genes are assembled during lymphocyte
      development by a novel, highly regulated series of gene rearrangement reactions
      known as V(D)J recombination. All rearranging loci are flanked by conserved
      heptamer-nonamer recombination signal sequences. Gene rearrangement results in
      the imprecise fusion of coding sequences and the precise fusion of signal
      sequences. DNA molecules with double-stranded breaks near signal sequences have
      been detected in cells undergoing V(D)J recombination of the TCR delta locus. We
      have devised a ligation-mediated PCR assay that detects broken-ended molecules in
      purified genomic DNA. Using this assay we found that DNA breaks occurring
      precisely at the signal sequence-coding sequence junction are a general feature
      of V(D)J recombination, appearing in association with each type of rearranging
      immunoglobulin gene segment. We show that a significant fraction of these broken
      ends are blunt and 5'-phosphorylated. In addition, detection of these broken
      ended signal sequences is dependent on the activity of RAG-1 and RAG-2, and is
      restricted to the G0/G1 phase of the cell cycle. The pattern of broken-ended
      molecules detected in cells at various stages of development reflects the
      activity of the V(D)J recombinase at different loci during B- and T-cell
      development.

PMID- 8276237
TI  - torso-like encodes the localized determinant of Drosophila terminal pattern
      formation.
AB  - Differentiation of the anterior and posterior poles of the Drosophila embryo
      requires seven maternally expressed genes including torso-like (tsl) and torso
      (tor). The tor gene encodes a receptor tyrosine kinase that is expressed
      throughout the embryo but is activated specifically at the poles. Genetic mosaic
      analysis has shown that tsl is required during oogenesis in follicle cells at
      each end of the oocyte. We cloned the tsl locus and showed that it was expressed
      specifically in follicle cells at the anterior and posterior ends of the oocyte.
      tsl encodes a novel protein with a putative amino-terminal signal sequence.
      Ectopic expression of tsl produced embryos with a phenotype similar to that
      resulting from constitutively active Tor alleles. These results suggest that
      localized TSL controls the localized activation of TOR.

PMID- 8276238
TI  - The DNA-binding domain of p53 contains the four conserved regions and the major
      mutation hot spots.
AB  - Mutations in the p53 tumor suppressor gene are the most commonly observed genetic
      alterations in human cancer. The majority of these mutations occur in the
      conserved central portion of the gene, but there has been little information
      about the function of this region. Using proteolytic digestion of the 393-amino
      acid human p53 protein, we have identified a 191-amino-acid protease-resistant
      fragment (residues 102-292) that corresponds to the central portion of p53, and
      we show that this core fragment is the sequence-specific DNA-binding domain of
      the protein. DNA binding is inhibited by metal chelating agents, and we find that
      the core domain contains zinc. Proteolytic digests also reveal a 53-amino-acid
      carboxy-terminal domain which we show to be the tetramerization domain of p53.

PMID- 8276239
TI  - A proteolytic fragment from the central region of p53 has marked sequence
      specific DNA-binding activity when generated from wild-type but not from
      oncogenic mutant p53 protein.
AB  - p53 is a sequence-specific DNA-binding oligomeric protein that can activate
      transcription from promoters bearing p53-binding sites. Whereas the activation
      region of p53 has been identified within the amino terminus, the location of the
      specific DNA-binding domain has not been reported. Thermolysin treatment of p53
      protein generates a stable protease-resistant fragment that binds with marked
      specificity to p53 DNA-binding sites. Amino-terminal sequencing of the fragment
      located the thermolysin cleavage site to residue 91. Because the fragment does
      not contain the cdc2 phosphorylation site at Ser-315, we conclude that the the
      site-specific DNA-binding domain of p53 spans the central region of the protein.
      The vast majority of the mutations in oncogenically derived p53 proteins are
      located within this central portion of the molecule. Such mutant p53 proteins
      exhibit defective sequence-specific DNA-binding. Although thermolysin digestion
      of mutant p53 proteins generates proteolytic patterns that differ from wild-type
      protein, one mutant tested, His-273, generates a resistant fragment that migrates
      with a similar electrophoretic mobility to the wild-type protease-resistant
      fragment. Interestingly, although intact mutant His-273 protein binds to DNA at
      20 degrees C, the thermolysin-resistant mutant fragment does not. In addition,
      the central protease-resistant, site-specific binding region of wild-type p53
      does not demonstrate nonspecific DNA-binding. Thus, although sequences outside of
      the central region of p53 contribute to both nonspecific DNA-binding and
      oligomerization, they are not required for sequence-specific DNA-binding.

PMID- 8276240
TI  - p53 domains: identification and characterization of two autonomous DNA-binding
      regions.
AB  - We have investigated the DNA-binding, oligomerization, and trans-activation
      functions of isolated segments of murine p53. We find that p53 has two autonomous
      DNA-binding regions. One domain, from amino acid 280 to 390, forms stable
      tetramers and binds DNA nonspecifically. The biological significance, if any, of
      this DNA-binding activity is not known. A second domain, from amino acid 80 to
      290, does not form stable tetramers under stringent conditions but binds DNA both
      specifically and nonspecifically. The specific DNA-binding function of p53,
      therefore, resides in the highly conserved central region of the protein and does
      not require stable tetramerization. Amino acids 1-290, which include both the
      specific DNA-binding domain and the amino-terminal acidic region, activate a p53
      specific promoter in vivo. This finding strongly argues that the DNA-binding
      activity of p53 segment 80-290 is physiologically significant. The role of
      tetramerization in p53 function remains to be determined.

PMID- 8276241
TI  - Molecular cloning and characterization of dTAFII30 alpha and dTAFII30 beta: two
      small subunits of Drosophila TFIID.
AB  - The multisubunit transcription factor TFIID is an essential component of the RNA
      polymerase II initiation apparatus. Recent studies suggest that TFIID subunits,
      or TAFs associated with the TATA-binding protein (TBP), play a critical role in
      modulating transcriptional activation by sequence-specific DNA-binding factors.
      Thus far, six of the largest TAFs associated with Drosophila TFIID have been
      cloned and partially characterized. Here, we report the molecular cloning,
      expression, and subunit interaction specificities of two small molecular mass
      TAFs. Both dTAFII30 alpha and dTAFII30 beta are associated with TFIID via
      interactions with other TAFs, including dTAFII250, dTAFII150, and dTAFII110. In
      addition, dTAFII30 alpha also contacts dTBP. The carboxy-terminal half of
      dTAFII110 was found to contact a short 67-amino-acid region of dTAFII30 alpha,
      which is predicted to form two potential alpha-helices, one of which is
      amphipathic. Interestingly, dTAFII30 alpha also appears to multimerize through
      its carboxy-terminal region. Although neither dTAFII30 alpha nor dTAFII30 beta
      have been found to interact with specific activators thus far, it is intriguing
      that both bind other TAFs such as dTAFII110 and dTAFII150, which are the targets
      of activation domains. Our studies suggest that both of the small subunits of
      TFIID play a role in the assembly of the complex and may contribute to the
      stability of multiple TAF-TAF interactions.

PMID- 8276242
TI  - General splicing factor SF2/ASF promotes alternative splicing by binding to an
      exonic splicing enhancer.
AB  - The general splicing factor SF2/ASF binds in a sequence-specific manner to a
      purine-rich exonic splicing enhancer (ESE) in the last exon of bovine growth
      hormone (bGH) pre-mRNA. More importantly, SF2/ASF stimulates in vitro splicing of
      bGH intron D through specific interaction with the ESE sequences. However,
      another general splicing factor, SC35, does not bind the ESE sequences and has no
      effect on bGH intron D splicing. Thus, one possible function of SF2/ASF in
      alternative and, perhaps, constitutive pre-mRNA splicing is to recognize ESE
      sequences. The stimulation of bGH intron D splicing by SF2/ASF is counteracted by
      the addition of hnRNP A1. The relative levels of SF2/ASF and hnRNP A1 influence
      the efficiency of bGH intron D splicing in vitro and may be the underlying
      mechanism of this alternative pre-mRNA processing event in vivo.

PMID- 8276243
TI  - IGF-I is required for normal embryonic growth in mice.
AB  - IGF-I is a pleiotropic hormone reported to affect linear growth, glucose
      metabolism, organ homeostasis, and the immune and neurologic systems. In contrast
      to IGF-II, IGF-I is expressed at low levels embryonically and has been thought to
      be more important for postnatal growth and development. To investigate the role
      of IGF-I in normal development we generated mice with an inactive IGF-I gene by
      homologous recombination in ES cells. Heterozygous mice are healthy and fertile,
      but they are 10-20% smaller than wild-type littermates and have lower than normal
      levels of IGF-I. The size reduction is attributable to a decrease in organs and
      muscle and bone mass. However, all tissues appear histologically normal. At birth
      homozygous mutant mice (IGF-I-/-) are < 60% body weight of wild type. Greater
      than 95% of IGF-I-/- pups die perinatally. Histopathology is characterized by
      underdevelopment of muscle tissue. Lungs of late embryonic and neonates also
      appeared less organized with ill-defined alveolae. IGF-I appears to be essential
      for correct embryonic development in mice.

PMID- 8276244
TI  - The activity of sigma E, an Escherichia coli heat-inducible sigma-factor, is
      modulated by expression of outer membrane proteins.
AB  - sigma E and sigma 32 are two heat- and ethanol-inducible sigma-factors in
      Escherichia coli. The sigma 32 regulon is also induced by unfolded and misfolded
      proteins in the cytoplasm, and the function of many of the proteins in the sigma
      32 regulon is to bind to cytoplasmic proteins and assist them in folding or
      unfolding. To further understand the function of the sigma E regulon, we searched
      for mutants that affected sigma E activity. Our results indicate that a signal
      generated by expression of outer membrane proteins modulates sigma E activity.
      Specifically, sigma E activity is induced by increased expression of OMPs and is
      reduced by decreased expression of OMPs. In addition, mutations that cause
      misfolded OMPs induce sigma E activity. This signal is generated after the fate
      of OMPs and periplasmic proteins diverge in the secretory pathway and is not the
      result of an accumulation of OMP precursors in the cytoplasm. Our results
      indicate that this effect of OMPs is specific to the sigma E regulon, because
      none of the above mutations affect sigma 32 activity. We propose that the sigma E
      regulon is involved in processes that occur in extracytoplasmic compartments and
      that these two heat-inducible regulons may have distinct but complementary roles
      of monitoring the state of proteins in the cytoplasm (sigma 32) and outer
      membrane (sigma E).

PMID- 8276245
TI  - Isolation and characterization of an Escherichia coli mutant defective in
      resuming growth after starvation.
AB  - To understand the mechanisms that allow the enteric bacterium Escherichia coli to
      make the transitions between growth and stationary phase and to maintain cell
      viability during starvation, we have looked for mutants defective in stationary
      phase survival (a Sur- phenotype). In this paper we describe a conditional E.
      coli mutant, surB1, that grows normally and remains viable during stationary
      phase but is unable to exit stationary phase and resume aerobic growth at high
      temperature. Thus, the surB gene product is not required for cell survival per se
      but, rather, it is required for starved cells to reinitiate growth under
      restrictive conditions. Once growth has started, SurB function is no longer
      required. Mutant cells sense and respond to fresh medium but appear to arrest
      growth before the first cell division. The surB gene was mapped to 19.5 min on
      the E. coli chromosome, cloned, and sequenced. The surB gene product is predicted
      to be an integral membrane protein with multiple membrane-spanning regions and is
      homologous to the ATP-binding cassette (ABC) family of transporters, a large
      family of transport proteins found in both prokaryotic and eukaryotic cells. An
      open reading frame, designated ybjA, was found immediately upstream of surB and
      may be in an operon with surB. The predicted ybjA gene product is also homologous
      to the ABC transporter family and SurB and YbjA may function together in a common
      transport pathway. Either surB or ybjA may be the same gene as cydC, a gene
      described previously whose function is needed for the production of functional
      cytochrome d oxidase complexes. Consistent with this prediction, surB1 mutant
      cells were found to lack functional cytochrome d oxidase. However, the SurB-
      phenotype is not simply attributable to the absence of cytochrome d oxidase.
      Thus, the surB gene product may have an additional role in the cell.

PMID- 8276246
TI  - Temporal and spatial association of histone H2A variant hv1 with
      transcriptionally competent chromatin during nuclear development in Tetrahymena
      thermophila.
AB  - Vegetative cells of the ciliated protozoan Tetrahymena thermophila contain a
      transcriptionally active macronucleus and a transcriptionally inactive
      micronucleus. Although structurally and functionally dissimilar, these nuclei are
      products of a single postzygotic division during conjugation, the sexual phase of
      the life cycle. Immunocytochemical analyses during growth, starvation, and
      conjugation were used to examine the nuclear deposition of hv1, a histone H2A
      variant that is found in macronuclei and thought to play a role in
      transcriptionally active chromatin. Polyclonal antisera were generated using
      whole hv1 protein and synthetic peptides from the amino and carboxyl domains of
      hv1. The transcriptionally active macronuclei stained at all stages of the life
      cycle. Micronuclei did not stain during growth or starvation but stained with two
      of the sera during early stages of conjugation, preceding the stage when
      micronuclei become transcriptionally active. Immunoblot analyses of fractionated
      macro- and micronuclei confirmed the micronuclear acquisition of hv1 early in
      conjugation. hv1 staining disappeared from developing micronuclei late in
      conjugation. Interestingly, the carboxy-peptide antiserum stained micronuclei
      only briefly, late in development. The detection of the previously sequestered
      carboxyl terminus of hv1 may be related to the elimination of hv1 during the
      dynamic restructing of micronuclear chromatin that occurs as the micronucleus
      enters a transcriptionally incompetent state that is maintained during vegetative
      growth. These studies demonstrate that the transcriptional differences between
      macro- and micronuclei are associated with the loss of a chromatin component from
      developing micronuclei rather than its de novo appearance in developing
      macronuclei and argue that hv1 functions in establishing a transcriptionally
      competent state of chromatin.

PMID- 8276247
TI  - Chromatin structure: mapping proteins associated with genomic DNA using
      crosslinking.
AB  - The structure and structural dynamics of chromatin and nucleosomes in
      transcription and replication were studied by DNA-protein crosslinking. A general
      strategy has been designed and a number of methods have been developed to map
      proteins bound to the genomic DNA, to sequence the arrangement of such proteins
      along DNA in multi-protein complexes, and to identify interacting nucleotides and
      amino acid residues. Perspectives for large-scale mapping of proteins associated
      with genomic DNA are discussed.

PMID- 8276248
TI  - Chromatin structure and the expression of globin-encoding genes.
AB  - The developmental regulation of globin gene expression in the chicken has been
      studied. All of the genes are regulated by a small number of general erythroid
      factors. In addition, expression of individual members of the family must be
      controlled in a lineage (stage)-specific manner. In some cases, the relevant
      factors may be stage specific, but in others they are not confined to one stage,
      but exert their control through developmentally regulated changes in their
      abundance within the nucleus. Chromatin structural elements, such as locus
      control regions and insulators, are also involved in control of eukaryotic gene
      expression. Because so much is understood about regulation of individual genes,
      the globin family has proven valuable in investigating control of transcription
      at the level of chromatin structure.

PMID- 8276249
TI  - Searching for replication origins in mammalian DNA.
AB  - The attempts at identifying precise replication origins (ori) in mammalian DNA
      have been pursued mainly through physico-chemical and biochemical approaches, in
      view of the essential failure of the search for autonomously replicating
      sequences in cultured cells. These approaches involve the mapping of short
      stretches of nascent DNA, the identification of the regions where either leading
      or lagging strands switch polarity, or the localization of replication
      intermediates by two-dimensional gel electrophoresis. Due to the complexity of
      animal cell genomes, most of these studies have been performed on amplified
      domains and with the use of synchronization procedures. The results obtained have
      been controversial. In order to avoid the use of experimental procedures
      potentially affecting the physiological mechanism of DNA replication, we have
      developed a method for the localization of ori in single-copy loci in
      exponentially growing cells. This method entails the absolute quantification of
      the abundance of selected DNA fragments along a genomic region within samples of
      newly synthesized DNA by competitive polymerase chain reaction (PCR); the latter
      is immune to all the uncontrollable variables which severely affect the
      reproducibility of conventional PCR. The application of this method to SV40 ori
      driven plasmid replication precisely identifies the known ori localization. Using
      the same approach, we have mapped an ori for bi-directional DNA replication in a
      13.7-kb locus of human chromosome 19 encoding lamin B2.

PMID- 8276250
TI  - On the ancient nature of introns.
AB  - We discuss some of the arguments for introns arising early or late in evolution.
      We outline the exon theory of genes and discuss the series of discoveries of
      introns in the gene (TPI) encoding triosephosphate isomerase (TPI) that have
      filled out a series of better fits to the Go plot, culminating in the 1986
      prediction of an intron position that was finally discovered in 1992. We present
      a statistical argument that the 11-intron structure of TPI (based on attributing
      all of the introns to an ancestral gene and interpreting three cases of very
      close intron positions as examples of sliding) has a clear relationship to the
      protein structure. The exons of this 11-intron TPI are a better approximation to
      Mitiko Go's modules (Go, 1981) than are 99.9% of all alternative exon patterns
      corresponding to 11 introns placed randomly in the gene, and better than 96% of
      all alternative patterns in which the lengths of the exons are preserved while
      the introns are moved. We combine four tests relating exons to protein structure:
      (i) whether the exons are compact modules, (ii) whether the exons contain most of
      the close contacts in the protein, (iii) whether the exon configuration maximized
      buried surface area along the backbone, and (iv) whether the exons maximize their
      content of hydrogen bonds. On a joint measure for these tests, the native exon
      structure with 11 introns fits these tests better than 99.4% of all alternative
      structures obtained by permuting the exon lengths and intron positions.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276251
TI  - Co-chairman's remarks: genetic recombination in the molecular era.
AB  - The present status of some general questions about DNA recombination is assessed.
      Topics include the mechanisms of synapsis and strand exchange, and the functions
      of recombination in nature.

PMID- 8276252
TI  - Looking backwards: a birthday card for the double helix.
AB  - This 'birthday' paper outlines very briefly the history of the discovery of the
      DNA double helix, the way it was received and how it was confirmed. The paper
      also discusses why, at that time, we foresaw so little of the rapid progress
      produced by the techniques of recombinant DNA. The key feature of the nucleic
      acids--discovered by Jim Watson--is their ability to form specific base pairs.

PMID- 8276253
TI  - Analysis of a viral integration event in a CG-rich region at the 1p36 human
      chromosomal site.
AB  - The preinsertion site of an adenovirus-5/simian virus 40 recombinant construct
      (Ad5/SV40) has been cloned and sequenced. Our data suggest that viral integration
      has occurred in a genomic region which has been the target of multiple events of
      Alu element retropositions within a TAA minisatellite. Extensive homologies
      between the left viral end and the host cellular DNA were also observed. The
      compositional similarity between Adenoviridae and the region of viral integration
      is consistent with the observed insertion of exogenous DNA in isochores of
      similar composition [G. Bernardi, Annu. Rev. Genet. 23 (1989) 637-661].

PMID- 8276254
TI  - Mechanisms of illegitimate recombination.
AB  - Illegitimate recombination, which is one of the major causes of genome
      rearrangements, can occur in a number of ways. These might involve enzymes which
      cut and join DNA or enzymes which replicate DNA, as illustrated by two examples:
      (i) formation of deletions at the replication origin (ori) of an Escherichia coli
      bacteriophage, M13; and (ii) excision of E. coli transposon Tn10. It is proposed
      that a common theme to various ways by which illegitimate recombination can occur
      might be the capacity to create ends in the DNA molecule and to make the ends
      meet.

PMID- 8276255
TI  - The immunoglobulin kappa locus-or-what has been learned from looking closely at
      one-tenth of a percent of the human genome.
AB  - The immunoglobulin kappa locus and its immediate surroundings, which are
      described in the present report, comprise 3 Mb of DNA, i.e., 0.1% or one per mill
      of the 3000 Mb of the human genome. Based on the work of our group during the
      past 12 years, we can now (1) depict in much detail the structure of the kappa
      locus with its 76 V kappa genes and pseudo genes, five J kappa elements and one C
      kappa gene; (2) specify the size of the germ-line repertoire of kappa light
      chains, which is one of the sources of the practically unlimited antibody
      diversity; (3) assign the known transcription products (studied as cDNAs) and
      kappa proteins to certain germ-line V kappa genes and attribute the differences
      in sequences to hypermutation and, to a lesser extent, to allelic variation; (4)
      analyze the hypermutation patterns which may contribute to the understanding of
      this enigmatic process; (5) describe the V kappa-J kappa rearrangements for half
      of the V kappa genes by a deletion mechanism and for the other half by a
      mechanism involving inversions of Mb-sized (i.e., 0.5 mm long) DNA fragments; (6)
      define various regulatory and other conserved sequence elements; (7) get clues as
      to the variation of the structure of the kappa locus in different individuals and
      populations, including a haplotype with only half the number of V kappa genes;
      (8) interpret many aspects of the evolution of the kappa locus in terms of
      duplications, insertions, deletions and gene conversions; (9) attribute the
      formation of the 24 V kappa orphons (i.e., genes outside the locus), whose
      sequences were determined, to pericentric inversions and other transposition
      processes; (10) answer a series of questions of biomedical interest; and (11)
      contribute 12.5 Mb of restriction maps, 1.8 Mb of clones and 250 kb of sequences
      to the elucidation of the human genome.

PMID- 8276256
TI  - Retroviral DNA integration: lessons for transposon shuffling.
AB  - Phylogenetic comparisons of retroviral IN (integrase) protein sequences have
      revealed homologies that extend to the retrotransposon and bacterial transposase
      families and have provided evidence for at least two functional domains. The N
      terminal region is characterized by a Zn-finger-like array which is conserved in
      retrotransposons. The central region is defined by a D,D(35)E amino acid
      constellation which is conserved through the retrotransposons and several
      bacterial IS element transposases. Mutagenesis studies and biochemical analysis
      of the isolated central D,D(35)E domain support our original suggestion that this
      region contains the catalytic center of these proteins which must all share a
      similar enzymatic mechanism. These, and other recent findings suggest unexpected
      relationships between diverse pathways of nucleic acid metabolism in eukaryotes
      and prokaryotes.

PMID- 8276257
TI  - LINE-1: a human transposable element.
AB  - Among the 10(5) LINE-1 sequences (L1Hs) in the human genome are one or more 6-kb
      segments that are active retrotransposons. Expression of these retrotransposons
      appears to be favored in cells of germ line origin, as well as in some other
      tumor cells of epithelial origin. In such cells, the product of the first L1Hs
      open reading frame (ORF), a protein called p40, is detectable; p40 has no
      apparent similarity to gag proteins, but contains a leucine zipper region which
      may be responsible for the occurrence of p40 multimers. Transcription of L1Hs
      initiates at residue 1 although the transcriptional regulatory regions are
      downstream in the first 670 bp of the 5' untranslated region; deletion of a YY1
      binding site in the first 20 bp reduces transcription by fivefold. Translation of
      the second ORF, which encodes reverse transcriptase, is independent of the
      translation of the frame encoding p40.

PMID- 8276258
TI  - Multistep evolution of B-cell-derived tumors in humans and rodents.
AB  - At least three genetic changes are known to contribute to the genesis of
      Burkitt's lymphoma (BL): the Ig/myc translocation, the presence of Epstein-Barr
      virus (EBV) in the vast majority of the endemic and a minority of sporadic
      tumors, and a p53 mutation, present in approximately 60% of the BL-derived lines.
      Activation of c-myc by juxtaposition to Ig sequences is a universal common
      denominator in endemic and sporadic EBV positive and negative BLs. It acts by
      preventing the cell from leaving the cycling compartment and by facilitating
      immune escape. EBV probably acts by expanding the target cell population at risk
      and prolonging its life span. This, together with the malaria co-factor, would
      increase the risk of the translocation accident. The p53 mutation may be
      essential for the continued growth of the tumors where it occurs, since
      introduction of wild-type p53 leads to their apoptotic death.

PMID- 8276259
TI  - Frederick Sanger, Erwin Chargaff, and the metamorphosis of specificity.
AB  - That a transformation of ruling ideas in genetics and biochemistry took place at
      the dawn of molecular biology, in the late 1940s, is a commonplace; but the
      nature and components of that transformation are widely misunderstood. The change
      is often identified with the importation into biology of new styles of thought
      and new rigor by the many scientists trained in physics or chemistry who came
      into the nascent field--notably, Max Delbruck, Max Perutz, Francis Crick, John
      Kendrew, Maurice Wilkins, Rosalind Franklin. Most generally, the change is
      supposed to be the realization that genes are made not of protein but of nucleic
      acid--and this change was initiated, of course, by the work of Oswald Avery and
      his colleagues. These changes are not mutually exclusive, and both were surely
      important to the genesis of molecular biology. But logically prior to them, more
      fundamental, was another transformation in ruling preconceptions, one that has
      been neglected: the revolution in understanding of the chemical structures--the
      sequences of subunits--of proteins and of nucleic acids which was wrought by the
      work of Frederick Sanger and of Erwin Chargaff. This was a metamorphosis in the
      understanding of biochemical specificity, and while it astonished many
      biochemists it set free the small groups of those who were beginning to call
      themselves molecular biologists, enabling them to think of the relationship
      between genes and proteins in entirely new ways.

PMID- 8276260
TI  - Somatic gene therapy for cancer: the utility of transferrinfection in generating
      'tumor vaccines'.
AB  - The last few years have seen the development of a branch of somatic gene therapy
      which aims at strengthening the immune surveillance of the body, leading to
      eradication of disseminated cancer tumor cells and occult micrometastases after
      surgical removal of the primary tumor. Such a tumor vaccination protocol calls
      for cultivation of the primary tumor tissue and the insertion of one of three
      types of genes into the isolated cultured tumor cells followed by irradiation of
      the transfected or transduced cells to render them incapable of further
      proliferation. The cells so treated constitute the 'tumor vaccine'. A review of
      the literature suggests that for mouse models, in the initial period after
      inoculation, rejection of the tumor cells is usually effected by non-T-cell
      immunity, whereas the long-term systemic immune response is based on cytotoxic T
      cells. High expression of the gene inserted into the tumor cells may be critical
      for the success of the vaccination procedure. Examples are given which indicate
      that transferrinfection, a procedure to introduce genes by adenovirus-augmented
      receptor-mediated endocytosis, meets some important prerequisites for successful
      application of this type of gene therapy.

PMID- 8276261
TI  - The molecular and genetic dissection of the retinoid signalling pathway.
AB  - Retinoids are derivatives of vitamin A (retinol) that exert a wide variety of
      profound effects on vertebrate development, cellular differentiation and
      homeostasis. How these simple molecules can exert such pleiotropic effects has
      recently been an area of intensive investigation. A complex array of
      combinatorial effects is beginning to emerge from molecular and genetic studies,
      which may ultimately account for the pleiotropic effects of retinoids.

PMID- 8276262
TI  - The mts1 gene and control of tumor metastasis.
AB  - The main stream of biology today is the analysis of the molecular mechanisms of
      major biological phenomena through studies of the genes governing these processes
      and their protein products. An example is the problem of tumor metastasis which
      is extremely important both theoretically and practically. Here we describe the
      data obtained on the detection, cloning, structure and transcription control of
      the mts1 gene, that encodes metastasin 1, a protein which seems to play an
      important role in the control of metastasis in mouse tumors. In particular, the
      experiments on tumor cell transfection with constructions containing either a
      sense or antisense mts1 sequence under a strong promoter/enhancer element show
      the direct dependence of the metastatic phenotype on the expression of the mts1
      gene at least in some systems. Gene mts1 encodes a protein belonging to the
      family of Ca(2+)-binding proteins and may be involved in the control of cell
      motility in different types of cells, such as macrophages and T-lymphocytes. The
      relationship between mts1 and other genes up- and down-regulated in metastatic
      cells is discussed.

PMID- 8276263
TI  - Molecular biology of flower development in Antirrhinum majus (snapdragon).
AB  - In recent years, isolation of several genes affecting flower development in
      Antirrhinum majus made this species a major model system to study this important
      developmental process. Genes like SQUAMOSA and FLORICAULA are involved in
      determination of the floral meristem. Their mutation results in the development
      of bract-forming shoots at positions where normally flowers would develop. The
      phenotypes obtained upon mutation of the genes found to affect floral
      organogenesis fall into three major categories. In each category, always the
      floral organs in two adjacent whorls become homeotically transformed. Based on
      this observation a simple genetic model has been proposed to explain the
      establishment of floral organ identity in the four concentric whorls of the
      flower. The model hypothesizes the independent induction of two developmental
      pathways specifying floral organ identity after the formation of sepals as the
      basic type of organ following induction of a floral meristem. One of these
      pathways is under the control of the PLENA gene, the other is controlled by the
      DEFICIENS and GLOBOSA genes. These genes, as well as SQUAMOSA, encode
      transcription factors sharing a conserved DNA binding domain: the MADS-box. In
      vitro DNA-binding studies complemented with molecular genetic analysis of the
      respective mutants show that the DEF and GLO proteins may act together in the
      form of a heterodimer in the regulation of their target genes as well as in
      autoregulation. The possible interactions between other MADS-box proteins and
      their role in flower development is under current investigation.

PMID- 8276264
TI  - Genes involved in the control of growth and differentiation in plants.
AB  - The mechanisms underlying totipotency, the unique ability of isolated plant cells
      to regenerate into plants, offer developmental biology a unique challenge. While
      it has been recognised for some time that phytohormones, such as auxin and
      cytokinin, play a role in this process by inducing a variety of growth patterns
      in both isolated cells, unorganised callus and intact plants, the molecular basis
      of their action remains unknown. The molecular and biochemical analysis of the
      novel interaction between tumour-inducing soil bacteria and the wounded plant has
      provided a valuable insight into how plants respond to phytohormones. During
      tumour formation, the bacteria transfer to the genome of the host plant a variety
      of genes which either short circuit the normal pathways of accumulation of
      phytohormones or modify how the plant cell responds to them. In parallel to these
      studies, we have been investigating plant genes involved directly or indirectly
      in the mechanism of phytohormone action. Auxin-binding proteins (putative
      receptors) have been localised in various cellular locations and the genes
      encoding them are currently undergoing analysis. Recently, a novel form of T-DNA
      has been devised by which mutant plant cell lines can be generated which grow in
      culture in the absence of exogenously applied auxin. The tagged genes, which are
      in effect plant cellular proto-oncogenes, are likely to shed more light on how
      auxin serves to regulate growth and development.

PMID- 8276265
TI  - What do we still need to know about transposable element Ac?
AB  - Transposable elements, originally discovered by Barbara McClintock, have been
      shown to occur in many if not all organisms. Their roles as selfish DNA
      (probable), as a major agent in evolution (unlikely) and as agents for the
      response to genomic stress (unclear) are discussed. Among the problems presently
      addressed are the mechanism of transposition and the regulation of transposition
      rate. The latter seems to differ in the Ac element of Zea mays compared to other
      transposable elements. The tendency of Ac transposase to form large aggregates is
      described, and the possible involvement of these aggregates in the control of the
      transposition rate is discussed.

PMID- 8276266
TI  - Co-chairman's remarks: the human genome project and cancer.

PMID- 8276267
TI  - Co-chairman's remarks: reverse genetics: directed modification of DNA for
      functional analysis.
AB  - The classic paradigm for identifying the genetic basis of a particular organism's
      properties proceeds from the phenotype to the gene, and thence to the molecular
      structures of the corresponding DNA, RNA and protein. 'Positional cloning' of
      disease genes and the molecular characterization of the responsible mutations
      (inappropriately referred to as reverse genetics, initially) exemplifies this
      approach. Now, the ability to clone, modify and test the biological activities of
      DNA segments provides a new approach, referred to as 'reverse genetics'. This
      paradigm begins with a segment of DNA whose molecular structure is known, and
      proceeds to explore the gene's contribution to the organism's phenotype; thus,
      the experimental path is from the gene as a nucleotide sequence to the
      corresponding phenotypic characteristic. Such a strategy follows from the ability
      to modify these sequences in highly directed and nearly unlimited ways, and to
      assess the phenotypic relevance of such alterations either in vitro, in cultured
      cells, or even in whole organisms. This approach permits the full panoply of
      molecular techniques to be used for creating uniquely altered structures and
      obviates the reliance on chance events as the source of mutations. As a
      consequence, the range of questions that can be studied is greatly expanded, and
      the information that is obtained is all the richer.

PMID- 8276268
TI  - cDNA analyses in the human genome project.
AB  - The ultimate goal of the human genome project is to decode all the genetic
      information carried in the genome. Towards this goal, the physical structure of
      the genome, as well as the functional aspects of the genome, must be understood.
      We initiated a cDNA project to collect the 'expression profiles' of all human
      genes, a database with which to describe which genes are expressed, and to what
      extent, in any given human cell at a particular time. Single-cycle sequencing of
      randomly selected members from a 3'-directed cDNA library is most appropriate for
      this purpose: the sequence data serve as a 'gene signature' to identify the
      expressing gene, and the frequency of appearance of the gene signature reflects
      the activity of the gene. The compiled data, which usually cover some 1000
      sequencing results per sample, are referred to as an 'expression profile.' We
      applied this analysis to HepG2 (a cell line derived from a hepatocellular
      carcinoma), liver cells and lung cells. The expression profiles shed some light
      upon the unique features of gene expression in the cell or tissue tested. A
      comparison of the expression profiles among different cells has allowed active
      genes to be classified as housekeepers or those with cell-specific functions. A
      significant fraction of the abundantly expressed genes include those that are
      unique to the cell. In addition, the resulting collection of thousands of gene
      signatures is a useful source of probes for mapping and for isolating full-size
      cDNAs.

PMID- 8276269
TI  - A second generation linkage map of the human genome based on highly informative
      microsatellite loci.
AB  - The use of simple sequence repeats as polymorphic genetic markers has
      considerably facilitated the construction of reference maps of the human
      chromosomes and mapping of Mendelian genetic diseases. These markers display
      major advantages over other systems and will be widely used for linkage mapping
      purposes in the forthcoming years.

PMID- 8276270
TI  - From the double-helix to novel approaches to the sequencing of large genomes.
AB  - Elucidation of the structure of DNA by Watson and Crick [Nature 171 (1953) 737
      738] has led to many crucial molecular experiments, including studies on DNA
      replication, transcription, physical mapping, and most recently to serious
      attempts directed toward the sequencing of large genomes [Watson, Science 248
      (1990) 44-49]. I am totally convinced of the great importance of the Human Genome
      Project, and toward achieving this goal I strongly favor 'top-down' approaches
      consisting of the physical mapping and preparation of contiguous 50-100-kb
      fragments directly from the genome, followed by their automated sequencing based
      on the rapid assembly of primers by hexamer ligation together with primer
      walking. Our 'top-down' procedures totally avoids conventional cloning,
      subcloning and random sequencing, which are the elements of the present 'bottom
      up' procedures. Fragments of 50-100 kb are prepared in sufficient quantities
      either by in vitro excision with rare-cutting restriction systems (including
      Achilles' heel cleavage [AC] or the RecA-AC procedures of Koob et al. [Nucleic
      Acids Res. 20 (1992) 5831-5836]) or by in vivo excision and amplification using
      the yeast FRT/Flp system or the phage lambda att/Int system. Such fragments, when
      derived directly from the Escherichia coli genome, are arranged in consecutive
      order, so that 50 specially constructed strains of E. coli would supply 50 end-to
      end arranged approx. 100-kb fragments, which will cover the entire approx. 5-Mb
      E. coli genome. For the 150-Mb Drosophila melanogaster genome, 1500 of such
      consecutive 100-kb fragments (supplied by 1500 strains) are required to cover the
      entire genome. The fragments will be sequenced by the SPEL-6 method involving
      hexamer ligation [Szybalski, Gene 90 (1990) 177-178; Fresenius J. Anal. Chem. 4
      (1992) 343] and primer walking. The 18-mer primers are synthesized in only a few
      minutes from three contiguous hexamers annealed to the DNA strand to be sequenced
      when using an over 100-fold excess of hexamers and T4 DNA ligase at room
      temperature, preferably in the presence of the single-strand-binding (SSB)
      protein of E. coli. These 18-nt primers are immediately extended by the DNA
      polymerase, Sequenase 2.0, in the dideoxy sequencing reaction. Very high quality
      sequencing ladders are obtained for single-stranded DNA or denatured double
      stranded approx. 50-kb fragments, as exemplified by phage lambda DNA.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8276271
TI  - Patenting cDNA 1993: efforts and happenings (Human Genome Project; NIH: US PTO;
      onco-mouse; European Patents).
AB  - The National Institute of Health (NIH) and Dr. J.C. Venter applied for patents
      for the sequences of cDNA fragments from a brain library. The scientific
      community objected strenuously on emotional grounds. The NIH argues that these
      sequences might never be patentable even when completed. The issue became an
      international one with the British applying for patents to protect their position
      while the French, Italians and Japanese vowed not to patent cDNA. The United
      States Patent Trademark Office (US PTO) strongly rejected the NIH's application.
      The NIH is appealing the decision.

PMID- 8276272
TI  - Lawyers' delights and geneticists' nightmares: at forty, the double helix shows
      some wrinkles.
AB  - The National Institutes of Health (NIH) request to patent the base sequences of
      incomplete and uncharacterized fragments of DNA copied on messenger RNAs (cDNAs)
      extracted from human tissues, the refusal by the patent office, and the appeal
      placed by NIH, have incited a violent controversy, fueled by rational, as well as
      emotional elements. In a compromising mode between liberalism and protectionism,
      I propose that legal protection be considered only for those RNA/DNA sequences,
      either natural or artificial, which can generate practical applications per se,
      and not through their expression products. Another controversy is developing
      around a popular tool for genomic research: the fidelity of yeast artificial
      chromosome (YAC) libraries being distributed worldwide for physical mapping is
      being questioned. Some of these libraries have been shown to be affected by
      surprisingly high levels of co-cloning, in addition to more common gene
      reshuffling instances. Also in this case, scientific as well as non-scientific
      components have to be considered. Possible remedies for the underlying problems
      may be found in the proper use of kinetic, enzymatic and microbiological
      variables in the production of YACs. Here too, a sharper distinction between the
      secular and scientific gratifications of research could help.

PMID- 8276273
TI  - Co-chairman's remarks: Jim Watson: the double helix, messenger RNA and the Human
      Genome Project--a personal view.

PMID- 8276274
TI  - Looking forward.
AB  - We are now entering the genome era of genetics, this phase being preceded by
      prior intellectual movements which gave the world: (1) Mendelian analysis, (2)
      DNA as the molecule of genetics, (3) the DNA-->RNA-->protein Central Dogma, (4)
      the molecular basis of gene expression and regulation, (5) the use of recombinant
      DNA procedures for gene isolation and manipulation, and (6) DNA sequencing and
      genome analysis. Soon, the human genetic information made possible by genome
      analysis will lead to subsequent logically following eras of predictive genetics
      and gene therapy.

PMID- 8276275
TI  - The efficiency and versatility of catalytic RNA: implications for an RNA world.
AB  - Because RNA is chemically and structurally dissimilar from protein, the finding
      of catalytic activity in RNA was initially surprising. Quantitative measurements
      of reaction rates show that RNA can be as efficient a catalyst as protein. On the
      other hand, the potential versatility of RNA to catalyze diverse types of
      reactions has only begun to be explored. Understanding the efficiency and
      versatility of RNA as a catalyst helps us evaluate origin-of-life scenarios
      involving self-replicating RNA, and may explain why RNA catalysis remains
      important in contemporary cells.

PMID- 8276276
TI  - The origin of genetic information: viruses as models.
AB  - A living entity can be described as a complex adaptive system which differs from
      any, however complex, chemical structure by its capability of functional self
      organization based on the processing of information. If one asks, where does this
      information come from and what is its primary semantics, the answer is:
      information generates itself in feedback loops via replication and selection, the
      objective being 'to be or not to be'. This paper describes the theoretical
      framework of information-generating systems and provides experimental clues for
      some basic forms of genetic organization, such as molecular quasi-species,
      hypercyclic and compartmentalized RNA-protein assemblies. The results are
      primarily obtained with RNA viruses and virus-like systems. The experiments are
      carried out with the help of automated, computer-controlled bioreactors, called
      'evolution machines', that may form the basis of a new 'evolutionary
      biotechnology'.

PMID- 8276277
TI  - Evolution of prokaryotic genomes.
AB  - Molecular genetics, which has its roots mainly in the development of microbial
      genetics in the middle of this century, not only greatly facilitates
      investigations of essential cellular functions, but also offers a means to better
      understand evolutionary progress. Spontaneous mutagenesis, the driving force of
      biological evolution, depends on a multitude of mechanistically distinct
      processes, many of which are already quite well understood. Often, enzymes act as
      variation generators, and natural gene vectors help to spread functional domains,
      entire genes and groups of genes across natural isolation barriers. In this
      overview, particular attention is given to comparing three selected natural
      strategies for the generation of genetic diversity: nucleotide substitution, DNA
      rearrangements, and gene acquisition. All of these mechanisms, as well as many
      others, appear to fulfill their specific roles in microbial evolution. Rather
      than being the result of an accumulation of errors, biological evolution may
      depend on a multitude of specific biological functions, as well as on a certain
      degree of intrinsic structural flexibility of biological molecules.

PMID- 8276278
TI  - Co-chairman's remarks: genetics and the twentieth century.
AB  - Genetics, the study of the gene, developed all through the twentieth century. It
      began with a search for mutations in a variety of organisms and the mapping of
      these mutations on chromosomes. Since it applied to humans, genetics became of
      interest to some of the ideologies that flourished during this century. In
      particular, eugenic ideas were used as an argument by the Nazis for the
      atrocities they committed in concentration camps. The gene long remained a 'being
      of reason', until the middle of the century, when it turned out to be made of
      DNA. In 1953, the discovery of the structure of DNA gave a completely new turn to
      genetics.

PMID- 8276279
TI  - The isochore organization of the human genome and its evolutionary history--a
      review.
AB  - This review will first present some properties (including compositional pattern,
      correlations between isochores and chromosomal bands, and gene distribution) of
      the human genome, the most extensively studied among vertebrate genomes. It will
      then explain how these properties came about during the evolution of the
      vertebrates.

PMID- 8276280
TI  - Bacterial plasmids: their extraordinary contribution to molecular genetics.
AB  - Reviewed here are certain of the extraordinary contributions to molecular
      genetics that have resulted from the study of bacterial plasmids. Work with
      plasmids has led to both the 'operon' and 'replicon' concepts, and has provided
      seminal information about bacterial conjugation and fertility, recombination,
      transposable genetic elements, genome evolution and antisense RNA. Studies of
      plasmid functions have yielded important findings about the regulation of DNA
      replication, DNA topology and partitioning, gene control signals and
      restriction/modification enzymes. Plasmids have had a central role in the
      development of DNA cloning (recombinant DNA) methods; additionally, they have
      provided a paradigm for both the co-transformation of non-selected DNA into
      eukaryotic cells and the creation of the artificial chromosomes.

PMID- 8276281
TI  - The denaturation of DNA.
AB  - Nucleic acids display a very characteristic ultraviolet absorption spectrum with
      a maximum near 260 nm and a minimum near 230 nm. It was discovered in 1950 that
      the spectrum of native DNA is much lower than the spectrum calculated from its
      constituent nucleotides (nt). The observed absorbance strongly increases
      (hyperchromic effect), not only following hydrolysis, but also following mild
      treatments, known to respect the phosphoester bonds between nt (and to have
      little effect on the molecular weight). These results show that DNA has a
      secondary structure made of secondary valence interactions between the nitrogen
      bases, and that this secondary structure collapses (DNA denaturation) following
      mild treatments (low pH, high temperature or, even simply, low salt
      concentration).

PMID- 8276282
TI  - Co-chairman's remarks: protein designs for the specific recognition of DNA.
AB  - The selective expression of a gene is achieved through the interaction of protein
      transcription factors with characteristic nucleotide sequences located in the
      regulatory region of the gene, which is usually distinct from the coding region.
      These proteins contain domains which bind specifically to the DNA sites (or
      response elements). Some general principles in the design of these DNA-binding
      domains are described, followed by examples of the different structural classes
      discovered so far and how they recognise their binding sites.

PMID- 8276283
TI  - Co-chairman's remarks: before the double helix.
AB  - In the nineteen-thirties and -forties, genes were universally believed to be made
      of protein. Biochemists met Avery, MacLeod and McCarty's discovery, that the
      transforming factor of pneumococci consists of DNA, with disbelief, and the
      notion that this was true of genes took a long time to be generally accepted even
      after Watson and Crick's discovery of its double helical structure. Until
      Watson's arrival, Kendrew, Crick and I were interested mainly in solving the
      structure of proteins, but Watson made us think about the structure of genes
      which determine protein structure.

PMID- 8276284
TI  - Cleavage site recognition by the tRNA splicing endoribonuclease.
AB  - A single tRNA-splicing endoribonuclease can cleave several precursors. In
      addition to the conserved nucleotides (nt), there are positions in the mature
      domain that, though not always occupied by the same nt, nevertheless play a
      fundamental role in intron excision reaction. The elements of the recognition set
      (invariant nt, nt at the cardinal positions) can contribute to the overall
      recognition process by providing either a direct contact for the enzyme or by
      dictating the spatial orientation of nt that are directly contacted.

PMID- 8276285
TI  - DNA comes in many forms.
AB  - Forty years ago, we learned of the major double helical structure adopted by DNA.
      It combined both elegance and simplicity in its design. Since then we have
      learned that DNA can also adopt other conformations. We now know that it can
      exist in a variety of triple-stranded and quadruple-stranded forms, as well as
      forms that are left-handed. The list of alternative conformations that can be
      adopted by this molecule is still growing. These conformations represent a major
      biological challenge to understand their role in biological systems. This type of
      work represents an active frontier in molecular biology today.

PMID- 8276286
TI  - Tumor oxygenation: a new predictive parameter in locally advanced cancer of the
      uterine cervix.
AB  - Experimental evidence suggests that hypoxia may increase the malignant potential
      and reduce the sensitivity toward nonsurgical treatment modalities in solid
      rodent tumors. However, the importance of tumor hypoxia in human malignancies is
      still uncertain. We have developed a clinically applicable standardized procedure
      for the determination of intratumoral pO2 in advanced cervical cancers by use of
      a computerized polarographic needle electrode histograph. To evaluate the
      significance of tumor oxygenation as a new oncologic parameter we initiated an
      open prospective clinical trial at the University of Mainz Medical Center in June
      1989. Until October 1992 50 patients with advanced cervical cancers entered the
      study. Tumor oxygenation measured in these 50 patients was independent from
      various patient and tumor characteristics, including hemoglobin concentration,
      FIGO stage, and tumor size. Thirty-three patients receiving standard radiotherapy
      with or without chemotherapy (RT +/- CT) were analyzed for treatment outcome.
      Intratumoral pO2 histography revealed median pO2 < or = 10 mm Hg (low pO2 tumors)
      in 15 of the 33 patients; in 19 tumors pO2 fractions < or = 5 mm Hg (low pO2
      fractions) were found. After a median follow-up of 24 months (range 6 to 40
      months) Kaplan-Meier life table analysis showed significantly shorter survival
      and recurrence-free survival for patients with low pO2 tumors treated with RT +/-
      CT. According to the Cox proportional hazards model the low pO2 fraction was the
      most powerful single predictor of survival and recurrence-free survival. The
      results of this study are consistent with the view that radiobiologically hypoxic
      tumors are less radiocurable but mechanisms of treatment failure other than the
      effect of hypoxia on the radiation response cannot be excluded. Intratumoral pO2
      histography in advanced cervical cancers enables pretherapeutic selection of low
      pO2 tumors as candidates for modified treatment approaches.

PMID- 8276287
TI  - Anatomical and pathological study of retroperitoneal nodes in epithelial ovarian
      cancer.
AB  - The pattern of lymphatic spread was evaluated in 81 previously untreated ovarian
      cancer patients (Stage I, 35; Stage II, 2; Stage III, 44) undergoing systematic
      aortic and pelvic lymphadenectomy. Positive nodes were found in 14% Stage I and
      68% Stage III patients. Either pre- and paraaortic, or pre- and paracaval nodes
      were the only aortic node metastasis in 14% of patients. Common iliac nodes were
      the sole metastasis in pelvic area in 11%, external iliac in 14%, and obturator
      in 6% of patients. Therefore, the above node groups, which overall were the most
      frequently involved, may be considered those primarily invaded by the tumor. When
      data were analyzed according to stage, aortic nodes were the site of metastasis
      in 6% Stage I and 14% Stage III patients and pelvic nodes in 8% Stage I and 11%
      Stage III patients. Both aortic and pelvic areas were positive in 43% Stage III
      patients. The median number of positive nodes/patient was 2 (range, 1-3) and 4
      (range 2-46) in Stages I and III, respectively. Lymphatic spread was ipsilateral
      to the tumor in all Stage I and in 40% Stage III patients. In Stage III
      metastases were also observed in intercavoaortic, retrocaval, retroaortic,
      internal iliac, and presacral nodes. In apparent Stage I, lymphatic metastasis
      seemed to be limited to one ipsilateral group, and the removal of the primary
      nodes ipsilateral to the tumor may be considered an adequate procedure. In Stage
      III, the presence of metastasis beyond the primary nodes and the frequent
      bilateral involvement suggest that all lymphatic tissue surround the aorta, the
      cava, and the pelvic vessels should be removed if a cytoreductive intent is
      pursued.

PMID- 8276288
TI  - Additive inhibition of RL95-2 endometrial carcinoma cell growth by carboplatin
      and 1,25 dihydroxyvitamin D3.
AB  - Responses of stage III/IV endometrial adenocarcinomas to cytotoxic agents have
      been partial and of short duration, results which indicate a need for new agents
      and therapeutic strategies. This study was undertaken to determine the effects of
      carboplatin and the active metabolite of vitamin D, 1,25 dihydroxyvitamin D3
      (calcitriol), on the growth of RL95-2 endometrial carcinoma cells. Carboplatin is
      a second-generation platinum-based cytotoxic agent. Calcitriol is a biologic
      agent that has activity against multiple solid tumors, including ovarian
      carcinomas. Carboplatin inhibited the growth of RL95-2 cells in a concentration
      dependent manner with maximal inhibition (78%) at 200 micrograms/ml. Calcitriol
      also inhibited RL95-2 growth in a concentration-dependent manner. Maximal
      inhibition (29%) was elicited by 80 nM calcitriol. Addition of 10-50 nM
      calcitriol to 5-20 micrograms/ml carboplatin resulted in improved growth
      inhibition. The degree of interaction between carboplatin and calcitriol was
      assessed using isobolographic analysis and was found to be additive at all drug
      concentrations and ratios examined. These results suggest that carboplatin and
      calcitriol each inhibit the growth of RL95-2 endometrial carcinoma cells and that
      the combination of these two agents acts additively to inhibit the growth of RL95
      2 cells. These agents merit further investigation for their utility against
      endometrial carcinomas.

PMID- 8276289
TI  - Papillary serous carcinoma of the peritoneal surface: matched-case comparison
      with papillary serous ovarian carcinoma.
AB  - Between 1984 and 1991, 199 patients underwent laparotomy for epithelial "ovarian"
      malignancy. In 29 cases (15%) normal-sized ovaries (< 4 cm in diameter) with
      minimal invasion by papillary serous carcinoma were found. This entity in the
      setting of peritoneal carcinomatosis has been previously described and is
      reported here as papillary serous cancer of the peritoneal surface (PSPS). The
      clinical, surgical, and pathologic features of PSPS are compared with a group of
      age-, grade-, and stage-matched cases with papillary serous ovarian carcinomas
      (PSOC). PSPS was also characterized by ascites (mean = 3036 cc), malignant
      washings (91%), and omental involvement with bulky infiltration and/or multiple
      tumor nodules (96%). Mean cytoreduction in the PSPS group was 65.5% compared to
      79% in the PSOC group (P = 0.049). Patients received combination chemotherapy
      with platinum-based regimens. In general, there was a poor response to treatment
      with a disease-free interval of 3.4 and median survival time of 19 months in PSPS
      compared to 11.7 and 31 months in the PSOC patients. Patients with PSPS have more
      limited cytoreduction, shorter disease-free interval, and shorter overall
      survival time. Such differences prompt re-evaluation of treatment modalities for
      PSPS and recognition that this is a condition distinct from PSOC.

PMID- 8276290
TI  - Whole-body positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose can
      detect recurrent ovarian carcinoma.
AB  - The existing means of detecting recurrent ovarian carcinoma are notoriously poor.
      Positron emission tomography (PET) is a form of computer-assisted imaging which
      produces images reflective of the biochemistry of the tissues rather than their
      physical characteristics. PET imaging with the positron emitting glucose analog 2
      [18F]-fluoro-2-deoxy-D-glucose (FDG) exploits the accelerated rate of glycolysis
      characteristic of malignant tissue to image tumors. To begin to study PET's
      ability to diagnose recurrent ovarian cancer, whole-body PET FDG scanning was
      performed on 13 patients prior to planned surgical exploration. Seven patients
      were suspected of having recurrence based upon clinical findings, and 6 patients
      were clinically free of disease. In all 6 of the patients with suspected
      recurrence who subsequently underwent surgery, PET images demonstrated increased
      FDG uptake in a distribution that correlated with surgical-pathologic findings.
      Both intraperitoneal and extraperitoneal lesions were detected by PET. All 6
      patients judged clinically free of disease had negative PET scans, but in 5 of
      these microscopic foci of residual tumor were found at surgery. Although PET FDG
      cannot replace surgery in the detection of microscopic recurrence, it can
      accurately detect tumors greater than 1.0 cm in diameter.

PMID- 8276291
TI  - High-dose cisplatin carboplatin chemotherapy in primary advanced epithelial
      ovarian cancer.
AB  - The purpose of the study was to maximize platinum dose intensity in women with
      ovarian cancer by combining cisplatin and carboplatin and using Day 1 and 8
      scheduling. Thirty-two consecutive patients with primary stage 3 or 4 epithelial
      ovarian cancer underwent radical cytoreductive surgery followed by high-dose
      cisplatin carboplatin chemotherapy. Twenty-eight tumors (88%) were stage 3C or 4
      and 20 (62%) were grade 3. Following radical cytoreductive surgery, 21 patients
      (66%) had less than 5 mm of residual disease. The first 2 patients treated with
      75 mg/m2 cisplatin and 150 mg/m2 carboplatin on Days 1 and 8 every 28 days for 5
      cycles developed severe and prolonged thrombocytopenia. As a result, the dose was
      reduced to 70 mg/m2 cisplatin and 100 mg/m2 carboplatin for the remaining 30
      patients, representing a monthly platinum dose of 207 mg/m2. Projected platinum
      dose intensity was 700 mg/m2 cisplatin and 1000 mg/m2 carboplatin delivered over
      16 weeks. Eleven patients (44%) received 100% and 27 patients (84%) received >
      90% projected platinum dose intensity. Median projected platinum dose intensity
      received was 97%. Grade 4 thrombocytopenia occurred in 43 cycles (28%) and grade
      3 peripheral neuropathy occurred in 15 patients (47%). Central nervous system
      toxicity occurred frequently: ototoxicity, 66%; decreased taste, 50%; optic
      toxicity, 41%; memory loss, 34%. Twenty-seven patients (84%) had a clinical
      complete response and 7 patients (44%) undergoing second-look laparotomy had a
      pathologic complete response. The majority of clinical responses were based on CA
      125. Median survival has not been reached at 2.1 years. Median progression-free
      survival is 1.4 years. Combining cisplatin and carboplatin using Day 1 and 8
      scheduling allows maximum hematologic platinum dose intensity; however,
      peripheral neuropathy is prohibitive. Day 1 and 8 scheduling does not appear to
      prevent peripheral neuropathy when delivering dose-intense platinum chemotherapy.
      Central nervous system toxicity of high-dose platinum is more common than
      previously reported.

PMID- 8276292
TI  - Lymph node yield from laparoscopic lymphadenectomy in cervical cancer: a
      comparative study.
AB  - Pretreatment surgical staging in cervical cancer has been studied extensively but
      remains controversial because a surgical procedure is required and the
      information gained may benefit only a small portion of the patients staged.
      Pelvic and paraaortic laparoscopic lymphadenectomies have been successfully
      performed in animal models and humans. Little information regarding the validity
      of the procedure in patients who have had subsequent laparotomy exists. In this
      series, we report our preliminary experience in 12 patients who underwent
      laparoscopic lymphadenectomy and then laparotomy. Overall, 377 pelvic nodes were
      removed, with 282 (75%) obtained at laparoscopy. The average number of pelvic
      nodes removed at laparoscopy was 23.5 (range 7-33). Two patients had positive
      pelvic nodes. No patient with negative nodes at laparoscopy had positive nodes at
      laparotomy. When studied in chronological order, the lymph node yield from our
      second 6 patients was much improved over our first 6 patients, 85% versus 63% (P
      < 0.005). Laparoscopy also proved to be a better predictor of lymph node spread
      than computed tomography. Two patients also had right-sided paraaortic
      lymphadenectomies, yielding 8 and 5 nodes. No additional right-sided paraaortic
      nodes were detected at laparotomy for either patient. In this preliminary series,
      laparoscopic lymphadenectomy appears to be a feasible procedure for surgical
      staging of cervical cancer. The yield of pelvic lymph nodes is adequate and
      improved with experience. Most importantly, no positive lymph nodes were missed
      by laparoscopy. The indications for operative laparoscopy have expanded rapidly.
      Gynecologic oncologists performing this procedure should be involved in
      prospective studies of this technique to set the standards and indications of
      this new technology.

PMID- 8276293
TI  - Cervical conization as definitive therapy for early invasive squamous carcinoma
      of the cervix.
AB  - Young women who present with stage Ia carcinoma of the uterine cervix may
      strongly desire preservation of fertility. There is little published information
      on the outcome of patients treated for early invasive cervical cancer with
      cervical conization. Patients were considered eligible for conservative
      management if they had a squamous lesion invading to a depth less than or equal
      to 3 mm with no lymphatic or vascular space involvement and negative margins. We
      identified 14 patients who had been treated by cervical conization alone for
      early invasive carcinoma of the cervix. Pathologic variables were reviewed for
      all patients. Patient records were retrospectively reviewed for demographic,
      pathologic, and follow-up information. The mean depth of invasion was 1.6 mm
      (range, 0.5-2.8 mm). The mean number of cone sections evaluated was nine (range,
      6-13 sections). The median follow-up period following conization was 26.5 months
      (range, 1-170 months). One patient underwent subsequent hysterectomy and was
      found to have mild dysplasia. Thirteen patients have retained their uteri and
      none has developed recurrent invasive or preinvasive lesions. We conclude that
      cervical conization is an acceptable therapy for selected cases of microinvasive
      squamous carcinoma of the uterine cervix. Larger studies of this patient group
      are indicated to confirm the safety of conization as definitive therapy in
      selected cases of early invasive cervical carcinoma.

PMID- 8276294
TI  - Assessment of primary and metastatic ovarian cancer by positron emission
      tomography (PET) using 2-[18F]deoxyglucose (2-[18F]FDG).
AB  - The potential of positron emission tomography (PET) to distinguish benign from
      malignant ovarian tissue was evaluated by comparing the results of F-18 fluoro-2
      D-deoxyglucose (F-18-FDG) PET scans with computed tomography and surgical
      findings. If sufficiently sensitive, this method might play a role in localizing
      metabolically active tumor sites for diagnosis, staging, and follow-up of ovarian
      cancer. Fifty-one patients had imaging studies prior to laparotomy for suspected
      ovarian cancer. PET scans were done with an ECAT 931-08-12 or ECAT EXACT (Model
      921, Siemens/CTI, Knoxville, TN) after iv injection of 185-370 MBq of F-18-FDG.
      (ECAT is a trade name for "emission computerized axial tomograph.") Data were
      acquired in dynamic scanning mode and time activity curves (TACs) were evaluated
      in multiple regions of interest identified by visual interpretation of the PET
      scans. Scan interpretation, standardized uptake values, and TAC profiles were
      related to surgical and histological findings. The results of this pilot study
      show good correlation between PET and histological findings. The positive
      predictive value of PET for ovarian cancer was 86% and, perhaps more important,
      the negative predictive value was 76%. This early work indicates that PET may be
      useful in the management of patients with ovarian neoplasms by identifying occult
      foci of metabolically active tumor that do not appear on morphological studies.

PMID- 8276295
TI  - Ovarian cancer screening in asymptomatic postmenopausal women.
AB  - From 1987 to 1992, 3220 asymptomatic postmenopausal women underwent screening
      with transvaginal sonography (TVS) as part of the University of Kentucky Ovarian
      Cancer Screening Project. Ovarian volume was calculated using the prolate
      ellipsoid formula (length x height x width x 0.523). An abnormal sonogram was
      defined by (1) an ovarian volume > 10cm3 or (2) a papillary projection into a
      cystic ovarian tumor. All women with an abnormal TVS had a repeat sonogram in 4-6
      weeks. If the repeat sonogram was abnormal, a morphology index score was assigned
      to each tumor, and a serum CA-125 was obtained. The patient then had a pelvic
      examination and an exploratory laparotomy. Forty-four patients (1.4%) with a
      persisting abnormality on TVS underwent exploratory laparotomy. Twenty-one
      patients had serous cystadenomas and 3 had primary ovarian cancers. Two patients
      with primary ovarian cancer had Stage IA disease and one had Stage IIIB disease.
      All patients with ovarian cancer had normal pelvic examinations and normal serum
      CA-125 levels, and are presently alive and well 32, 31, and 8 months after
      conventional therapy. Over 5000 screening years have been accumulated at this
      institution, and there have been no ovarian cancer deaths in the screened
      population. TVS screening has produced a decrease in stage at detection and case
      specific mortality from ovarian cancer. A multi-institutional trial to test the
      efficacy of TVS as a screening method for ovarian cancer is indicated.

PMID- 8276296
TI  - The effect of immediate intraperitoneal carboplatinum on wound healing.
AB  - The effect of introducing intraperitoneal carboplatinum on wound healing
      immediately after wound closure was studied using a rat model. All animals were
      opened through a midline incision. A bowel anastomosis was then performed in a
      single-or two-layer fashion using 6-O suture. Immediately after closing the
      abdominal wall, each animal was percutaneously injected with either normal saline
      for controls (n = 11), or carboplatinum, 3 (n = 8), 9, (n = 19, or 12 mg/kg (n =
      4). Abdominal and skin incisions were closed separately using 4-O silk suture.
      Animals were sacrificed 7 days postoperatively. Adhesions were blindly assessed
      on the following scale: 0 (no adhesions), 1 (filmy adhesions), 2 (firm
      adhesions), and 3 (dense adhesions). Anastomoses were assessed for leakage. Three
      centimeters of the incision were harvested to evaluate wound breaking strength.
      Analysis of abdominal wound breaking strengths showed control = 1320 g +/- 220, 3
      mg = 1055 g +/- 155, 9 mg = 891 g +/- 127, and 12 mg = 594 g +/- 165 (P < 0.025).
      Evaluation for dense adhesions resulted in control = 27%, 3 mg/kg = 50%, 9 mg =
      63%, and 12 mg = 100% (P < 0.0001). Immediate instillation of intraperitoneal
      carboplatinum had a significant effect on wound healing with a decrease in
      abdominal tensile strength directly related to the dose instilled. It also had a
      significant effect on adhesion formation with a higher dose leading to a higher
      incidence of adhesion formation. Based on animal model data, it appears that the
      immediate instillation of intraperitoneal carboplatinum at the time of laparotomy
      incision closure could lead to significant problems with wound strength and
      adhesion formation.

PMID- 8276297
TI  - Correlates of length of stay in gynecologic oncology patients undergoing
      inpatient surgery.
AB  - Escalating economic constraints require identification of the determinants of
      length of stay (LOS), since optimizing these may facilitate cost-effective care.
      However, risk factors for increased LOS are poorly understood. In order to
      identify correlates of long LOS, we retrospectively reviewed the charts of 252
      consecutive patients who underwent major inpatient surgery on the gynecologic
      oncology service at Barnes Hospital during 1990. Of these, 86 had benign disease
      and 38 were excluded for other reasons, leaving 128 for analysis. The recorded
      variables of age, race, medical history, measures of nutritional state, primary
      cancer, prior therapy, blood loss, operating time, and attending surgeon were
      subjected to regression analysis. In order to avoid reducing cell numbers to
      insignificant sizes, the linked factors of type of surgery and primary site were
      not analyzed simultaneously. A separate analysis was performed substituting type
      of procedure for primary site. The mean LOS was 12 days (range, 4-30). Five
      factors emerged as significant correlates of longer LOS: decreasing preoperative
      albumin level (P < 0.001) and hemoglobin level (0.029), increasing age (0.017),
      operative blood loss (0.039), and prior platinum-based chemotherapy (0.043).
      Presence of vulvar and fallopian tube primaries was associated with significantly
      shorter LOS (0.023 and 0.037). Together these factors accounted for 36% of total
      variance in LOS. Substituting procedure type for primary site accounted for 37%
      of total variance in LOS and showed that only bowel surgery (0.001) and
      preoperative intracavitary implant were significantly correlated with longer LOS.
      Factors not associated with LOS (P > 0.05) were race, attending physician, number
      of preoperative medications or medical conditions, body mass index, other
      radiotherapy, and other primary sites and procedures. Future studies should
      attempt to determine why elderly, nutritionally depleted women undergoing long or
      complicated procedures are at high risk for long LOS and should assess
      interventions designed to minimize LOS for this high-risk group.

PMID- 8276298
TI  - Peritoneal implant elimination during cytoreductive surgery for ovarian cancer:
      impact on survival.
AB  - A case-control study was performed to evaluate the potential benefit of
      peritoneal and serosal implant elimination (PIE) during primary cytoreductive
      surgery for patients with Stage IIIC epithelial ovarian cancer. Peritoneal
      implant excision and/or ablation was accomplished with electrocautery, CO2 laser,
      sharp dissection, argon beam coagulator, and cavitron ultrasonic surgical
      aspirator. Three groups of patients were compared: Group A (7 patients);
      macroscopically disease-free after cytoreduction without needing PIE; Group B (26
      patients); macroscopically disease-free after cytoreduction, including PIE; Group
      C (34 patients); macroscopic disease < or = 1 cm remaining exclusively on
      peritoneal surfaces with PIE not attempted. Each group had statistically
      equivalent mean ages, estimated blood loss, extent of disease, and variety of
      cytoreductive operations performed. Group B had a longer mean operating time than
      that of A or C (4.0 vs 2.8 hr P = 0.002). No serious morbidity occurred from PIE.
      Comparison of survival by log rank analysis and Cox proportional hazards
      regression shows a survival advantage for patients rendered free of macroscopic
      peritoneal implants (Group B vs Group C; P = 0.003). The result suggests that
      complete elimination of all visible peritoneal metastases might be of benefit
      during surgical cytoreduction for ovarian cancer if this renders the patient
      macroscopically disease-free. We also suggest the need of a randomized,
      prospective study to clarify the clinical role of PIE.

PMID- 8276299
TI  - Surgical management of groin node metastases from nonvulvar gynecologic
      malignancies.
AB  - Metastatic disease from nonvulvar gynecologic malignancies involving the groin
      lymph nodes is uncommon. The purpose of this study is to analyze the morbidity,
      recurrence-free interval, and survival in this group of surgically managed
      patients. Twenty patients underwent surgical resection of metastatic disease
      involving the groin lymph nodes between January 1, 1984 and December 31, 1991.
      Individual factors which have an impact on morbidity, recurrence, and survival
      were analyzed. Two patients developed wound infection and 2 had wound breakdown.
      Both of the patients with postoperative wound infection had clinically fixed
      nodes. None of the patients developed deep venous thrombosis. Long-term
      complications included lymphocytes in 2 patients and lymphedema in 4 patients.
      The median local disease progression-free interval was 10 months, with 5 of 20
      patients developing local recurrence. The overall median survival was 11 months,
      with an adjusted 5-year survival rate of 11.5%. Patients with clinically fixed
      lymph nodes had a shorter median survival (3.6 months) than those with clinically
      mobile (median, 22.6 months) nodes (P = 0.0032). Metastatic disease from
      carcinoma of the ovary, fallopian tube, uterus, and cervix involving the groin
      lymph nodes can be managed safely and effectively with surgical resection. The
      acute and long-term morbidity is acceptable. Local control can be achieved in the
      majority of patients.

PMID- 8276300
TI  - Are borderline tumors of the ovary overtreated both surgically and systemically?
      A review of four prospective randomized trials including 253 patients with
      borderline tumors.
AB  - The optimal treatment of early-stage ovarian borderline tumors is controversial.
      Only a few randomized trials evaluating adjuvant treatment for this disease have
      been published. Between 1970 and 1988 four consecutive randomized trials,
      including patients with ovarian borderline tumors, were conducted at the
      Norwegian Radium Hospital. After surgery, 253 stage I-II borderline tumors
      without residual disease were randomly allocated to these protocols. The adjuvant
      treatment in the four trials consisted of [1] external irradiation (Ext) combined
      with intraperitoneal instillation of radioactive gold (198Au) or Ext alone, [2]
      intraperitoneal radioactive therapy followed by thio-TEPA or no further
      treatment, [3] thio-TEPA or no adjuvant therapy, and [4] cisplatin or 32P
      treatment. The patients were equally distributed according to prognostic
      variables within the eight randomization groups. The overall corrected and crude
      survival were 99 and 94%, respectively. In 83% of the patients a hysterectomy,
      bilateral salpingo-oophorectomy, and omentectomy was performed. None of the
      patients with less extensive surgery relapsed. Adjuvant therapy did not seem to
      improve the overall corrected survival. On the contrary, toxicity was added with
      small bowel complications after radiation therapy, neurotoxicity after cisplatin
      treatment, and bone marrow toxicity after thio-TEPA therapy. It is concluded that
      stage I borderline tumors should not receive any adjuvant treatment.

PMID- 8276301
TI  - Thoracic vertebral bone metastasis from uterine leiomyosarcoma.
AB  - We report a patient with solitary thoracic vertebral bone metastasis (Th 8) from
      uterine leiomyosarcoma. The vertebral metastatic lesion was treated surgically,
      and vertebral body replacement with ceramic prosthesis and anterior spinal
      stabilization were performed. Such aggressive surgical intervention for solitary
      vertebral bone metastasis may contribute to the improvement of prognosis and
      maintenance of general quality of life in the patient.

PMID- 8276302
TI  - Laparoscopically assisted radical vaginal hysterectomy.
AB  - A vaginal or a laparoscopic approach in radical surgery for cervical carcinoma
      has been proposed. A pilot study of eight cases shows that an oncologic surgeon
      familiarized with these techniques is able to take advantage of the benefits of
      both routes in the same patient: laparoscopic surgery is adapted to lymph node
      dissection, section of the origin of the uterine artery, and dissection of the
      ureter under direct vision; vaginal surgery allows a precise incision of the
      vaginal cuff. Both routes may be used for the section of parameters, but we
      propose the use of the vaginal route. The combination of vaginal and laparoscopic
      surgery spares the pain and discomfort of both laparotomy and perineotomy.

PMID- 8276303
TI  - Breast carcinoma metastatic to uterine leiomyoma.
AB  - A case report of a woman with a history of breast carcinoma who presented with
      metastatic infiltration of uterine leiomyoma is described. The previously
      published literature on the subject is reviewed.

PMID- 8276304
TI  - Acute tumor lysis syndrome with squamous cell carcinoma of the vulva.
AB  - Acute tumor lysis syndrome (ATLS) is a rare metabolic complication in
      nonhematologic malignancies. We report a unique case of extensive regionally
      recurrent squamous cell carcinoma of the vulva who developed a picture compatible
      with ATLS 36 hr after the initiation of palliative chemotherapy. The patient
      suffered acute renal failure with hyperuricemia, hyperphosphatemia, and
      hypocalcemia as well as a picture suggestive of congestive heart failure. The
      patient responded well to adequate hydration, alkaline diuresis, and allopurinol.
      The potential for ATLS should be anticipated when treating metastatic or locally
      advanced squamous cell carcinoma of the vulva with chemotherapy.

PMID- 8276305
TI  - Documentation of complete resolution of gestational choriocarcinoma in the
      oophorectomized patient.
AB  - A 39-year-old woman with choriocarcinoma metastatic to the lungs and parametrium
      underwent total abdominal hysterectomy/bilateral salpingo-oophorectomy and follow
      up chemotherapy with regression of the hCG assay, plateauing at 9 mIU/ml. Spinal
      fluid hCG assay was negative. An LH assay was performed which was 135 mIU/ml (2nd
      IRP-HMG). A quantitative hCG assay was performed on two sources of purified LH at
      varying concentrations to determine the contribution of LH cross-reactivity. When
      corrected for the LH contribution, the quantitative hCG was zero. Chemotherapy
      was discontinued. At 12-months follow-up the patient has remained in complete
      chemical remission and has an excellent performance status. Whenever a patient is
      oophorectomized, LH cross-reactivity should be ruled out as a cause for
      persistent low titers of hCG.

PMID- 8276306
TI  - Late recurrence of clear cell adenocarcinoma of the vagina and cervix: a report
      of three cases.
AB  - Three patients with clear cell adenocarcinomas who developed recurrent disease
      after a prolonged disease-free interval are presented. The first patient
      developed a recurrence in the lung 7 years and 3 months after wide local excision
      and pelvic radiotherapy for clear cell adenocarcinoma of the vagina. She then
      underwent thoracotomy and chemotherapy and has remained free of disease for more
      than 13 years after treatment of the recurrence. The second patient with clear
      cell adenocarcinoma of the vagina developed recurrent disease at the apex of the
      vagina 5 years after radical hysterectomy, bilateral pelvic lymphadenectomy, and
      partial vaginectomy. She then underwent exploratory laparotomy, partial
      vaginectomy, and vaginal irradiation and has been free of disease in follow-up
      for 6 months. The third patient underwent radical hysterectomy, bilateral pelvic
      lymphadenectomy, and total vaginectomy for clear cell adenocarcinoma of the
      cervix that also involved two-thirds of the vagina. Four years and 6 months after
      this operation, she underwent an exploratory laparotomy, with complete resection
      of recurrent disease in the abdomen in continuity with a left nephrectomy.
      Following surgery, she was treated with abdominal and pelvic radiotherapy and
      chemotherapy and remained clinically free of disease for 1 year, but subsequently
      developed an unresectable pelvic mass. Despite further chemotherapy, she died 5
      years and 10 months after the initial diagnosis.

PMID- 8276307
TI  - Merkel cell carcinoma of the vulva.
AB  - We present the clinical, histopathologic, and ultrastructural features of a
      primary vulvar Merkel cell carcinoma. This tumor appears to have a more
      aggressive behavior than those at other anatomic sites. A review of reported
      cases is presented. Preoperative evaluation and the role of surgery,
      radiotherapy, and chemotherapy in the management of these tumors are discussed.

PMID- 8276308
TI  - Specific rearrangements of human papillomavirus DNA provide molecular evidence
      for genetic heterogeneity of primary cervical cancers, recurrencies, and lymph
      node metastases in two patients.
AB  - Two different characteristic patterns of human papilloma virus (HPV) type 16 DNA
      were found by Southern blot hybridization in four pelvic and paraaortic lymph
      node metastases in a patient with FIGO stage IIIb cervical cancer. Both patterns
      added up to give the HPV 16 DNA pattern of the primary tumor. This strongly
      suggests that the tumor was composed of two distinct compartments, each spawning
      its own lymph node metastases. A second patient presented with a vaginal tumor 4
      years after stage IIb cervical cancer had been treated with hysterectomy only.
      The vaginal tumor was removed and pelvic lymphadenectomy performed. Integrated
      HPV 16 DNA was found in the vaginal tumor whereas one involved and one free lymph
      node contained episomal HPV 16 DNA with a characteristic deletion. The apparent
      heterogeneity of the cancer cell population may indicate that the metastasis is
      not related to the vaginal tumor but that it is a late sequel of the cervical
      cancer. Alternatively the metastasis could have originated from an unsampled
      portion of the vaginal tumor.

PMID- 8276309
TI  - Detection and patterns of treatment failure in 300 consecutive cases of early
      endometrial cancer after primary surgery.

PMID- 8276310
TI  - Correlation between HPV positivity and state of the p53 gene in cervical
      carcinoma cell lines.

PMID- 8276311
TI  - Surgical training in gynecologic oncology affects outcome.

PMID- 8276312
TI  - Ovarian cancer staging: does it require a gynecologic oncologist?

PMID- 8276313
TI  - Paraaortic lymphadenectomy.

PMID- 8276314
TI  - 111In-CYT-103 immunoscintigraphy in ovarian cancer.

PMID- 8276315
TI  - Effect of long-term aerobic exercise on helium-neon-laser-induced thrombogenesis
      in rat mesenteric arterioles and platelet aggregation.
AB  - We have previously investigated the antithrombotic effect of aerobic exercise in
      rat arterioles and venules under conditions of variable exercise load. In the
      present study, rats were subjected to constant exercise of 90% maximal oxygen
      uptake for 30 min, 5 times a week for 2, 4, 8 or 18 weeks. Thrombotic tendency
      was assessed by the He-Ne-laser-induced thrombus formation method. Platelet
      aggregation, platelet adhesion, whole blood clotting time, fibrinogen levels and
      blood cell count were also measured. The thrombotic tendency in arterioles
      decreased significantly after 18 weeks training, but not in venules. Thrombotic
      tendency increased slightly after 2 weeks training though the differences were
      not significant. A significant decrease in collagen-induced platelet aggregation
      was observed after 18 weeks training. The results demonstrated that long-term
      aerobic training decreased the thrombotic tendency in rat arterioles and that
      this was partly due to decreased platelet aggregability.

PMID- 8276316
TI  - Anticoagulation with nafamostat mesilate, a synthetic protease inhibitor, in
      hemodialysis patients with a bleeding risk.
AB  - Nafamostat mesilate (FUT) is a synthetic serine protease inhibitor with a short
      half-life that is used during hemodialysis (HD) in patients with a high risk of
      bleeding because it does not prolong the systemic coagulation time. To evaluate
      whether or not FUT is able to effectively prevent clot formation in the
      extracorporeal circuit without increasing systemic bleeding, HD using FUT was
      carried out for 33 sessions in 12 patients with a high risk of bleeding. FUT was
      continuously infused during HD at 20-40 mg/h to maintain a 2-fold prolongation of
      activated partial thromboplastin time (APTT) at the dialyzer outlet on the venous
      side of the circuit. No APTT prolongation was observed on the arterial side of
      the circuit before FUT infusion, and none of the patients showed increased
      bleeding during or after HD. However, clots formed in the arterial chamber
      (30.3%), the dialyzer (36.6%), and the venous chamber (15.1%). In 2 of the 12
      patients, HD was discontinued due to clot formation despite sufficient
      prolongation of APTT. The mean levels of the thrombin-antithrombin III complex
      and prothrombin activation fragment 1 + 2 in the circuit gradually increased on
      both the arterial and venous sides during HD using FUT, and protein C activity
      decreased. No significant changes in these parameters occurred during heparin HD
      in the same patients after the bleeding episode had resolved. Despite sufficient
      prolongation of APTT in the circuit, FUT was less effective in suppressing
      thrombin generation when compared to heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276317
TI  - Coagulation, fibrinolytic and kallikrein systems in neonates with uncomplicated
      sepsis and septic shock.
AB  - This study evaluates the contact system, coagulation inhibitors and fibrinolysis
      in 23 full-term newborns with sepsis (8 with septic shock). The results were
      compared with a group of 20 healthy newborns. Blood samples were obtained at the
      time of clinical diagnosis and 3 days after the antibiotic therapy was started.
      The results showed that: severe infection was associated with activation of the
      contact system, depletion of anticoagulant proteins and elevation of C4b-binding
      protein levels. There was a shift in protein S to the complexed inactive form,
      and the thrombin-antithrombin complexes increased. These changes occurred in
      parallel to both activation and inhibition of fibrinolysis. These changes were
      more pronounced in the septic shock patients than in nonshock neonates. After
      therapy, this procoagulant state decreased among survivor patients while in those
      who died, the abnormalities in coagulation did not improve. Our study suggests
      that neonatal sepsis induces a hypercoagulable state that persists in nonsurvivor
      neonates despite a correct treatment.

PMID- 8276318
TI  - Decreased high-molecular weight fibrinogen and impaired alpha-chain
      polymerization in full-term newborns.
AB  - Some properties of fibrinogen from 30 newborn and 30 normal adult plasmas
      obtained under the same conditions have been studied. The results show that the
      high-molecular weight fibrinogen (HMW-Fg) was decreased by nearly 25% in newborn
      plasma as compared to normal adult values. The kinetics of fibrin gel formation
      was decreased in newborn as compared with normal adult plasmas (gelation rates
      2.2 +/- 1 vs. 5.6 +/- 0.5 x 10(-4) OD/s, lag time 128 +/- 25 vs. 72 +/- 3 s). The
      release rates of fibrinopeptide A (FPAp +/- FPA) and fibrinopeptide B (FPB) were
      decreased in newborn fibrinogen (FPAp + FPA 10.8 and FPB 1.2 x 10(-3) s-1) as
      compared to normal adult fibrinogen (FPAp + FPA 11.8 and FPB 1.7 x 10(-3) s-1).
      Analysis by SDS-PAGE of the reduced, highly cross-linked fibrin from the newborns
      showed that only 23% of the alpha-chain participates in the formation of alpha
      chain polymers. The results suggest that the retarded release rate of
      fibrinopeptides and the decrease in the HMW fibrinogen concentration are causes
      of the prolonged kinetics of fibrin gel formation in newborns.

PMID- 8276319
TI  - Protein S and C4b-binding protein levels in patients with stroke: implications
      for protein S regulation.
AB  - Protein S circulates either free or bound to C4b-binding protein (C4b-BP). Only
      free protein S possesses cofactor activity for protein C, a physiologic
      anticoagulant. Deficiencies of either protein C or protein S are associated with
      increased thrombotic risk. Over a 23-month period, 40 patients with low free
      protein S were identified. Eight of these patients were found to have suffered a
      stroke. This study examined the relationship between total S, free S, and C4b-BP
      in 15 healthy adult volunteers, in 20 patients with normal protein S levels, in
      40 patients with decreased free protein S levels, and in 8 patients with combined
      low free S levels and stroke. Total and free protein S and C4b-BP levels were
      determined using the method of Laurell. In healthy adults, free protein S
      increased with increasing total protein S (r = 0.60). In patients with normal
      free S, the total S level increased as C4b-BP increased (r = 0.74), and the free
      S level remained constant. In patients with low free S, total S did not increase
      with increasing C4b-BP. In stroke patients, the correlation between free S and
      total S was actually negative (r = -0.449). Evaluation of dissociation constants
      for the protein S-C4b-BP complex revealed enhanced binding in patients with low
      levels of free protein S. A non-C4b-BP protein S binding protein, a previously
      undescribed regulatory factor which modulates S binding to C4b-BP, or shifts in
      the amount of non-protein S binding C4b-BP are possible explanations of these
      results.

PMID- 8276320
TI  - Evaluation of the coagulation/fibrinolysis balance in patients with colorectal
      cancer.
AB  - The coagulation and fibrinolysis profile was evaluated in 40 patients with newly
      diagnosed untreated colorectal carcinoma (24 males, 16 females; 29 patients
      without and 11 patients with metastases). Fibrinogen, von Willebrand factor
      antigen, FVIII:C, thrombin-antithrombin III complex (TAT III), fibrin monomers
      (FM), plasminogen activator inhibitor-1 (PAI-1) and D-dimers were tested. None of
      the patients had clinical or laboratory evidence of serious hemorrhage or
      thrombosis. The results of global routine coagulation tests (aPTT, PT) were not
      significantly changed. Significant elevations were found for median fibrinogen,
      von Willebrand factor antigen, FVIII:C, TAT III and D-dimers, compared with a
      healthy reference group. These results confirm earlier reports of an enhanced
      level of both coagulation and fibrinolysis markers in carcinoma patients and
      might be helpful in trying to understand the impact of several relatively new
      sensitive coagulation and fibrinolysis parameters in colorectal cancer. Moreover
      the position of the coagulation/fibrinolysis balance might be an explanation for
      the elevated incidence of thrombotic events in patients with cancer.

PMID- 8276321
TI  - Reduced fibrinolytic activity in glomeruli isolated from rabbits infused with
      tumor necrosis factor.
AB  - Glomerular fibrin deposition may result from local activation of blood
      coagulation and/or impaired removal by the fibrinolytic system. We evaluated the
      fibrinolytic activity of glomeruli isolated from rabbits infused for 5 h with
      tumor necrosis factor (TNF) at the doses of 0.8 micrograms/kg/h (n = 5) and 8
      micrograms/kg/h (n = 3) or with endotoxin (8 micrograms/kg/h, n = 7). Animals
      infused with vehicle (n = 11) served as control group. Plasminogen activator (PA)
      activity of glomerular extracts from rabbits infused with 8 micrograms/kg/h of
      TNF or endotoxin was significantly lower than that of samples from control
      animals (p = 0.013 and p = 0.003, respectively). At the dose of 0.8
      micrograms/kg/h, TNF caused a reduction in glomerular PA activity which, however,
      did not reach statistical significance. Neither plasminogen-independent activity
      nor PA inhibitor activity was detected in glomerular extracts. Fibrin autography
      of control extracts revealed the presence of two main fibrinolytic activities
      comigrating with purified urokinase-type and tissue-type PAs. In treated samples,
      the bands corresponding to free PAs were markedly reduced, with no evidence of
      enzyme-inhibitor complex formation. Local reduction of fibrinolytic capacity may
      contribute to intraglomerular fibrin deposition during endotoxemia or in renal
      inflammatory diseases associated with TNF production.

PMID- 8276322
TI  - Comparative study on the antithrombotic efficacy of hirudin, heparin and a low
      molecular weight heparin in preventing experimentally induced venous thrombosis.
AB  - In a random, blind study, we compared the antithrombotic potential of
      unfractioned heparin, a low-molecular weight heparin (LMWH) and a recombinant
      hirudin (r-hirudin) given subcutaneously in a jugular vein thrombosis model in
      rabbits. All drugs and placebo were injected subcutaneously 2 h before inducing
      experimental thrombosis. A good thromboprophylactic effect was obtained with
      either LMWH and r-hirudin as compared with placebo. By contrast, no significant
      differences were found between groups in bleeding time. We also found a small
      (non-significant) prolongation of the activated partial thromboplastin time in
      the r-hirudin-treated animals. As for thrombin time, r-hirudin-treated rabbits
      exhibited too much sensitivity, with noncoagulable end-points. In our study, r
      hirudin at the dose used seemed to be as effective as LMWH is in the prophylaxis
      of venous thrombosis.

PMID- 8276323
TI  - The pathology of the claustrum in Galloway syndrome indicates the existence of
      claustro-entorhinal pathway.
AB  - The morphology of the claustrum in Galloway syndrome was investigated. Galloway
      syndrome is a rare autosomal recessive disease that causes microcephaly and is
      associated with kidney pathology. The brain examined was small, and the external
      surface of the hemispheres was lissencephalic, with an abnormal gyrification
      pattern. The whole cerebral cortex showed severe pathological changes, but the
      most affected area was the cortex lying on the medial aspect of the temporal
      lobe, especially the entorhinal cortex. In addition, the paraamygdalar and
      temporal parts of the claustrum were intensively changed. These results may
      confirm the opinion that the claustrum is a cortico-dependent structure and that
      the limbic cortex receives large projection from its ventral parts.

PMID- 8276324
TI  - The preoptic area in the sexually immature pig. Morphological study.
AB  - The preoptic area was investigated in 5 immature pigs. This area is composed of
      three nuclei: lateral, medial, and median. The largest is the lateral nucleus.

PMID- 8276325
TI  - The hypoglossal nucleus in human embryos at the end of 4th week (stage 13).
AB  - The hypoglossal nucleus in embryos at stage 13 extends through the medulla
      reaching upper cervical segments of the spinal cord. It is formed by elongated
      group of cells in the ventral part of the basal plate. From the nucleus arise
      five thick roots which enter the occipital somites.

PMID- 8276326
TI  - The sinuatrial nodal artery in the human heart.
AB  - Studies were performed on 12th hearts taken from cadavers of adults of both
      sexes. The corrosive technique was used. Arteries were filled with vinyl
      polychloride or Plastogen G from the side of aortic sinuses. The sino-atrial
      nodal artery arose as the anterior, intermediate and posterior atrial branches
      both from the right coronary artery and the left coronary artery. In 51.7% of the
      hearts the sino-atrial nodal artery formed the arterial circle at the base of the
      superior vena cava.

PMID- 8276327
TI  - The investigations of mechanical properties of ossificating thyroid cartilages of
      the human larynx.
AB  - 40 thyroid cartilages were used to investigations, they were taken from bodies of
      people, died between the ages of 19-99, by the use of the endurance machine with
      controlled speed of the increase of deformation. It was observed that the
      durability for flexion and the inflexibility of the investigated cartilages
      depends on the level of the process of their ossification, that is estimated by
      the help of the radiological index of the ossification (RIO). On the other hand,
      the searches of durability forcing of the regions of cartilages that presented
      different levels of the ossification process, proved the heterogenicity of the
      structure of the cartilage, in which ossified parts are separated by zones, that
      did not submit to this process.

PMID- 8276328
TI  - Ossification of human thyroid cartilage. Scanning electron microscopic study.
AB  - The architecture of the cartilage already developed within ossified areas have
      shown apparent differences not only depending on their location within cartilage
      territory but also due to their chemical composition. The cartilage areas
      exhibiting a markedly advanced ossification process have shown rather high
      concentration level of Ca, P and Si.

PMID- 8276329
TI  - The atrioventricular nodal artery in the human heart.
AB  - Studies were performed on 120 hearts taken from adult cadavers of both sexes. In
      the study,. prepared and corrosion technique was used. Arteries were filled with
      vinyl polichloride or Plastogen G through the aorta. The examined vessels were
      dissected and either partly, or totally etched in the concentrated hydrochloric
      acid soda lye. The arterial blood supply of the atrioventricular node arose in
      108 (90%) of the hearts from the right coronary artery and in 12 (10%) of the
      hearts from the left coronary artery.

PMID- 8276330
TI  - Blood vascular organization of the walls of vermiform appendix from human fetus.
      Examination of vascular corrosion casts in SEM.
AB  - Ten human vermiform appendices obtained from fetal corpses (160.0-240.0 mm of
      CRL) were examined using injection-micro corrosion method. Blood vascular bed
      reproduced with this method was observed with scanning electron microscope (SEM).
      Blood vascular bed structure of foetal appendix has been described,
      simultaneously with produced by them plexuses and organisation of
      microcirculation in a wall of the appendix. Collected results have been compared
      with data of other authors who conducted similar research on adult human
      appendices and appendices of several animal species.

PMID- 8276331
TI  - The vascularization of the conducting system of the atria of the heart in
      relation to the type of coronary ramification.
AB  - On 12th randomized specimens of the human heart, of either sex, from 19-84 years
      of age, I investigated the vascularization of the conducting system of the heart
      in relation to the type of coronary ramification, by the dissection and injection
      corrosive method. The symmetrical type of arterial vascularization was
      established in 47.5%, the right type in 45% and the left type in 7.5% of the
      cases investigated. Most often the right anterior sinus nodal artery was in the
      symmetrical type and the left anterior sinus nodal artery in the right type of
      arterial supply. The right atrioventricular nodal artery was in 90% of the hearts
      in the right and symmetrical type of the arterial vascularization.

PMID- 8276332
TI  - Sources of blood supply and angioarchitecture of nerves in limbs of the white
      rat.
AB  - Sources of blood supply and structure of vascular network were described in
      nerves of forelimbs and hindlimbs of 30 Wistar strain rats. The vessels were
      injected through the left ventricle of the heart with aqueous solution of
      gelatin, stained with black ink. Following fixation in formaldehyde samples were
      taken at various points of the median, ulnar, radial, musculocutaneous, femoral,
      nerves and their terminal branches. The preparations were made translucent in
      methyl benzoate. The observations point to constant sources of regional vessels
      supplying nerves of forelimbs and hindlimbs and to a similar angioarchitecture of
      studied nerve trunks at their entire length. Branches of regional vessels which
      enter the nerves form a fine mesh network in epineurium. Within nerve fascicles
      capillary network forms a uniform cord of vessels, the structure of which
      resembles that of human sciatic nerve.

PMID- 8276333
TI  - Studies on density of capillary network in the course of nerves in the white rat.
AB  - Density of capillary network was examined in the course of nerves of frontal and
      rear extremities in the white rat, in various portions of the nerves. At the same
      levels, number of nervous fibers per mm2 of the area was scored as well as
      diameters of myelinated fibers was recorded in proximal and distal fragments of
      chosen nerves. Decreased density of capillary network was detected in peripheral
      portions of the nerves, which was paralleled by an increase in number of
      myelinated fibers and a decrease in their diameter.

PMID- 8276334
TI  - The vestibulocochlear ganglion in human embryos at stage 13.
AB  - In embryos at stage 13th vestibulocochlear ganglion forms a complex structure
      with the geniculate ganglion. The geniculate ganglion is placed rostrally and may
      be distinguished from the vestibulocochlear ganglion. Also at this stage there is
      a sign of differentiation of the vestibular and cochlear ganglia.

PMID- 8276335
TI  - [Phenylketonuria--change in therapeutic strategies. Study of intellectual
      development and dietary compliance of young phenylketonuria patients].
AB  - Recent results of research appear to show that over the past few years, clearly
      more restrictive dietary recommendations have become accepted in the treatment of
      phenylketonuria (PKU). A lifelong diet low in phenylalanine is the goal, since
      poor dietary discipline can lead to an appreciable decrease in the level of
      intelligence and, in rare cases, to severe neurological deficits. Furthermore,
      neuropsychological symptoms as sequelae of current high serum phenylalanine
      levels also occur. In the present study, the question as to the development of
      intelligence and compliance with diet was investigated. The results underscore
      the need for continuing adherence to a diet on the one hand, and for continuous
      psychosocial support on the other.

PMID- 8276336
TI  - [Correlation between hyperplastic and adenomatous polyps of the colon].
AB  - PROBLEM: Although hyperplastic polyps are considered to be non-neoplastic, they
      nevertheless have a number of characteristics in common with adenomatous polyps.
      STUDY DESIGN: Since hyperplastic polyps and adenomas frequently occur together,
      the question arises as to whether hyperplastic polyps, found for example during
      sigmoidoscopy, might not be an indicator of possibly neoplastic polyps in the
      more proximal part of the bowel. In a retrospective analysis of first-time total
      colonoscopies in 685 patients, we investigated the relationship between
      hyperplastic and adenomatous polyps. RESULTS: Twenty-one patients proved to have
      only hyperplastic polyps in the rectosigmoid, while 12 of these patients (11.8%)
      also had adenomatous polyps in the more proximal parts of the colon. In contrast,
      30.8% of the patients (n = 109) with rectosigmoidal adenomas also had adenomas in
      the more proximal colon. Irrespective of histology, as the size of rectosigmoidal
      polyps increased, so did the percentage of patients with adenomas in the proximal
      colon--from 22.4% in the case of small polyps not exceeding 5 mm in diameter to
      more than 31.2% in the case of polyps larger than 5 mm in diameter. When both
      hyperplastic and adenomatous polyps appeared together, hyperplastic polyps were
      found in larger numbers in the same or anatomically adjacent segment of the
      colon. CONCLUSION: The results of this study suggest that the presence of
      hyperplastic polyps in the rectosigmoid is not associated with an increase in the
      incidence of proximal adenomas, while rectosigmoidal adenomas must be considered
      indicators of adenomas in the more proximal parts of the bowel.

PMID- 8276337
TI  - [Virus infections--disease pictures and laboratory diagnosis. Part 1: Principles
      and practical references for diagnosis--adenoviruses, coronaviruses and coxsackie
      A virus].

PMID- 8276338
TI  - [Mianserin: pharmacology and clinical aspects of an effective antidepressive
      agents].
AB  - Among the non-tricyclic "newer" antidepressants, mianserin is one of the most
      thoroughly investigated agents. In the present review its chemical and
      pharmacological properties, as well as clinically relevant aspects of the use of
      this antidepressant are discussed. In the first instance, mianserin is indicated
      for the treatment of depressive illness associated with anxiety and agitation,
      even including severe forms of depression. Mianserin is characterised by a
      favourable side effect profile and low toxicity, and thus offers distinct
      advantages in the treatment of he elderly, as also in patients with a suicidal
      tendency.

PMID- 8276339
TI  - [Repair and expression of radiation injuries--recent trends on radiation cell
      biology].

PMID- 8276340
TI  - Effect of troponin T-treatment on the composition of rabbit skeletal myofibrils.
AB  - The effect of several conditions of troponin T-treatment was examined on the SDS
      gel electrophoretic patterns of rabbit skeletal myofibrils. More troponin C and I
      were removed from the myofibrils after troponin T-treatment at acidic pH (5.6
      6.2) than after treatment at neutral pH (6.8-7.4). Incubation of the myofibrils
      (0.4 mg/ml) in the presence of 0.043 mg/ml troponin T at a pH 6.2 for 60 min at
      25 degrees C resulted in the removal of most troponin C and I from the
      myofibrils. Troponin T1 (N-terminal 158 residue fragment of troponin T of 259
      residues) showed much lower troponin C.I removing activity than troponin T.

PMID- 8276341
TI  - [Production of monoclonal antibodies against osteoclasts of rat].
AB  - In mammals, it has been difficult to collect the authentic osteoclasts on a large
      scale. Recently we established a culture system for forming osteoclast-like
      multinucleated cells (MNCs) which exhibited many characteristics of osteoclasts.
      MNCs instead of authentic osteoclasts were used as immunogen to establish the
      hybridomas which secrete monoclonal antibodies against the osteoclasts by in
      vitro immunization. We obtained two monoclonal antibodies, HOK 1 and HOK 2. HOK 1
      showed intense immunoreactivity with MNCs, mononuclear cells and putative
      migratory traces of MNCs on the culture dishes, but it had weak reactivity with
      the stromal cells. HOK 2 also showed strong reactivity with MNCs, mononuclear
      cells, and the very limited area of the culture dishes just facing to one side of
      some MNCs. The stromal cells were faintly stained with HOK 2. In th paraffin
      sections of tibiae, both antibodies intensely stained osteoclasts, osteoblasts
      and osteocytes. The bone matrix was weakly stained by HOK 2 but not by HOK 1. The
      present observations indicated that HOK 1 and HOK 2 could recognize the common
      antigen expressed on cells both involving in the bone formation and resorption.
      The antigens recognized by HOK 1 and HOK 2 were shown to exist on the putative
      traces of motile MNCs. These antibodies would be available to investigate the
      mechanisms of the 'bone remodeling' as a functional marker of bone cells.

PMID- 8276342
TI  - [Multivariate analysis of mandibular morphology with fetal growth by means of the
      soft standardized radiographs].
AB  - Mandibular growth of the fetus is a great matter of importance to anatomy,
      anthropology and also oral and Maxillofacial surgery. The postnatal changes of
      the mandible that have occurred with growth have been reported by numerous
      investigators. However, a few researchers have investigated the prenatal growth
      of the mandible. The purposes of this study were discussed how to change in size
      and shape of the mandible during the fetal period. The materials consisted of 162
      human fetuses from the body length (BL) of 95 mm, to 500 mm. They were divided
      into four groups: 95-199 mm (BL1, N = 40), 200-299 mm (BL2, N = 76), 300-399 mm
      (BL3, N = 26), 400-500 mm (BL4, N = 20). All specimens were stored in formalin,
      and only those free from gross deformation were selected for study. The heads
      were removed by decapitation at the level of the hyoid bone. The soft
      standardized radiographs were taken of the frontal, lateral, basal aspects. They
      were used for tracing and angular and linear measurements (total thirty). The
      data were used to evaluate the mandibular form by multivariate analysis. They
      were supported the univariate analysis. The findings leads to the following
      conclusions: 1) Cluster analysis and principal component analysis were applied to
      the data to make clear the correlation between 30 variables. Four clusters were
      constructed at the level ninety similarities in cluster analysis. They were
      corresponded to four factors were obtained in principal component analysis. 2)
      The data were subjected to a stepwise discriminant function analysis using the
      seventeen of original 30 variables. Nine variables, mandibular length (Go-Me),
      mandibular ramus height (Col-Go), Symphyseal height (Id-Me), mandibular body
      height (Kr'-beta), gonial angle (< Co2, Go, Me), mental angle (< Id, Pog, Go),
      gonial width (BGo), alveolar width (BKr'), basal angle of mandible (< RGo, Me,
      LGo), were selected as the best discriminators. The incidence of correctly
      classified cases 88.68%. 3) As a result of the first discriminant function of the
      discriminant analysis and one-way analysis of variance (ANOVA) and t-test,
      mandibular length (Go-Me), gonial width (BGo), alveolar width (BKr'), Symphyseal
      height (Id-Me) were longer in tall group that short group (BL4 > BL3 > BL2 >
      BL1). Therefore, the first discriminant function was accounted for the size
      factor. 4) In consequence of the second discriminant function of the discriminant
      analysis and regression analysis, gonial width (BGo) was grown broader than
      alveolar width (BKr') from BL1 to BL2.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8276343
TI  - [The effects of lesions in the medial septal area to spatial learning in rats].
AB  - The effects of a disruption of the septo-hippocampal cholinergic system on
      learning behavior in rats were investigated. Learning was evaluated using an
      eight-arm radial maze task before and after electrolytic lesions in the medial
      septal area (MSA). The normal control rats gradually improved the task
      performance with an increase of trials and also developed a response strategy to
      select the arm adjacent to the one currently visited. The rats without any
      preoperative learning before the operation of MSA showed a persistent disturbance
      of task performance and the generation and development of the response strategy.
      On the other hand, rats which had performed learning trials before the operation
      of MSA only showed a transient disturbance of task performance which then rapidly
      recovered to the control level. The response strategy was also altered but
      immediately returned to the control pattern in this rat group. Acetylcholine
      esterase (AChE) activity was persistently depleted in the hippocampus by the MSA
      lesion. These results indicate that preoperative learning has a significant
      contribution to the task performance and the generation and development of the
      response strategy in rats with MSA lesions and that the septo-hippocampal
      cholinergic system plays an important role in this generation and development of
      the response strategy.

PMID- 8276344
TI  - [A case of NIDDM associated with oculomotor palsy due to atypical carotid
      cavernous sinus fistula].
AB  - Partial ophthalmoplegia due to third nerve palsy with an intact pupil is a
      frequent cause of diploplia observed in diabetic patients. Pupillary muscle
      involvement, such as anisocoria and loss of light reflex, is usually uncommon in
      this diabetic cranial mononeuropathy. A 65-year-old woman with non-insulin
      dependent diabetes mellitus (NIDDM) suddenly developed a severe headache and
      diplopla. Right oculomotor nerve palsy was observed in association with
      anisocoria, ptosis of the right lid, and a defective light reflex. No
      exophthalmos or vascular bruit was observed in the right orbital region. Computed
      tomography and magnetic resonance images of the head were negative. Cerebral
      angiography revealed a carotid cavernous sinus fistula (CCF). The patient was
      successfully treated with external carotid artery embolization combined with
      radiation. It is well known that pupil sparing in oculomotor nerve palsy predicts
      an extraaxial ischemic lesion, while pupil involvement predicts an extraaxial
      compression lesion. Therefore, pupillary involvement in oculomotor nerve palsy in
      diabetic patients necessitates cerebrovascular investigation to rule out ICPC
      aneurysm or tumor. In this circumstance, a variant type of CCF without
      characteristic ocular signs should be included in the differential diagnosis.

PMID- 8276345
TI  - Hepatic iron and zinc concentrations after portacaval shunting for nonalcoholic
      cirrhosis.
AB  - Hepatic iron and zinc concentrations were determined in 26 consecutive
      nonalcoholic cirrhotic patients who had previously undergone portacaval shunting
      and then liver transplantation and 37 control patients. Stainable iron was graded
      on a scale of 0 to 4; 11 shunt patients and 3 control patients had grade 2 to 4
      iron staining. Mean hepatic iron concentration was significantly increased (20.1
      +/- 4.1 mumol/gm) in the shunt group compared with the control group (9.1 +/- 2.3
      mumol/gm) (normal value, < 35 mumol/gm) (p = .015, Student's t test). Mean
      hepatic iron index (hepatic iron/age) was 0.5 +/- 0.10 in the shunt group and
      0.19 +/- 0.04 in the control group (p = 0.002). One shunt patient had a hepatic
      iron index of greater than 2. Hepatic zinc was not significantly different
      between the shunt group (2.42 +/- 0.18 mumol/gm) and the control group (2.56 +/-
      0.14 mumol/gm). Serial biopsy specimens were analyzed in 17 cases (6 shunt, 11
      controls), and the mean annual rate of iron accumulation was significantly
      greater in shunt patients (4.75 mumol/gm/yr) than in control cases (0.93
      mumol/gm/yr, p = 0.037). Although increased stainable iron was common after
      portacaval shunting, quantitative iron analysis demonstrated increased hepatic
      iron concentrations in only 6 of 26 shunt patients and 3 of 37 control patients
      (p = 0.14, chi 2 test). Quantitative hepatic iron analysis demonstrated in this
      study that portacaval shunt patients have far less accumulated iron than
      hemochromatosis patients and are unlikely to have tissue injury resulting from
      iron overload.

PMID- 8276346
TI  - Hepatic venular stenosis after orthotopic liver transplantation.
AB  - Fibrous stenosis of hepatic venules and other features of venous outflow
      obstruction, including zone 3 congestion and hemorrhage, are sometimes seen after
      orthotopic liver transplantation. similar changes associated with endothelial
      damage have recently been ascribed to azathioprine toxicity and may be
      forerunners of chronic rejection. Other potential causative agents such as viral
      hepatitis have yet to be considered. We reviewed 49 liver biopsy specimens from
      21 consecutive patients after orthotopic liver transplantation, in whom full data
      including further follow-up biopsy samples were available. Hepatic venous
      stenosis was identified in seven patients who had received azathioprine and two
      additional patients in whom this change could not be ascribed to azathioprine.
      Stenosis was always associated with zone 3 hemorrhage and congestion and was
      first noted between 5 and 30 days after transplantation in all but two cases; in
      these two patients they were first noted after 72 and 133 days. Cellular
      rejection, including endotheliitis involving terminal hepatic venules, was found
      in five of the seven patients who had received azathioprine. Chronic (ductopenic)
      rejection was not seen during a follow-up period of between 97 and 540 days. In
      three of the nine patients with hepatic venular stenosis, zone 3 changes
      persisted, and in two of these azathioprine could not be held responsible. Of the
      12 patients without hepatic venular stenosis, 10 had received azathioprine. Two
      of these 12 patients had peliosis-like foci but no other vascular abnormalities.
      Both also had moderate cellular rejection. Hepatic venular stenosis was found in
      43% of patients after liver transplantation; this was usually associated with
      azathioprine administration and concomitant cellular rejection.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276347
TI  - Relationship between plasma benzodiazepine receptor ligand concentrations and
      severity of hepatic encephalopathy.
AB  - Levels of benzodiazepine receptor ligands were measured in plasma samples from 25
      patients in various stages of hepatic encephalopathy due to fulminant liver
      failure who were not exposed to pharmaceutical benzodiazepines immediately before
      or during hospitalization. Chromatographic analysis of extracted plasma samples
      revealed one to nine fractions containing material that competitively inhibited
      [3H]flumazenil binding to benzodiazepine receptors with the pharmacological
      properties of benzodiazepine receptor agonists. Two of these peaks were
      positively identified as the 1,4-benzodiazepines diazepam and N-desmethyldiazepam
      on the basis of chromatographic, ultraviolet and mass spectral evidence. The
      plasma levels of diazepam and N-desmethyldiazepam were significantly increased
      above control values in stage 4 hepatic encephalopathy, whereas total
      benzodiazepine receptor ligand concentrations were increased above control in
      stages 1 through 4. A significant but weak linear correlation was found between
      the relative increase in the levels of diazepam, N-desmethyldiazepam and total
      benzodiazepine receptor ligands and the severity of hepatic encephalopathy. Thus
      increased concentrations of benzodiazepine receptor ligands appear to contribute
      to the enhancement of GABAergic neurotransmission in hepatic encephalopathy,
      particularly in stage 4. These results constitute further support for a role for
      benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy
      associated with acute liver failure.

PMID- 8276348
TI  - Transjugular intrahepatic portosystemic shunt worsens the hyperdynamic
      circulatory state of the cirrhotic patient: preliminary report of a prospective
      study.
AB  - The aim of this prospective nonrandomized study was to assess the immediate and
      short-term sequelae of transjugular intrahepatic portosystemic shunting on the
      circulatory hyperdynamic state of the cirrhotic patient. Twelve transjugular
      portosystemic shunting procedures were performed in 12 cirrhotic patients for
      sclerotherapy failure (10 cases) and/or intractable ascites (4 cases). Self
      expandable stents 10 mm in diameter were used in all cases. Portal pressure
      measurement and right-heart catheterization were performed before and 30 min and
      1 mo after the procedure. The portoatrial pressure gradient decreased from 15 +/-
      3 to 7 +/- 3 mm Hg 30 min after surgery (p < 0.0001) to 8 +/- 3 mm Hg 1 mo after
      surgery (p < 0.001, in comparison with basal values). The cardiac index increased
      from 4.5 +/- 1.3 to 5.7 +/- 1.5 L/min.m2 30 min after surgery (p < 0.001) to 7.4
      +/- 1.4 L/min.m2 1 mo after surgery (p < 0.001). Systemic vascular resistance
      decreased from 808 +/- 323 to 646 +/- 209 dyne.sec.cm-5 30 min after surgery (p <
      0.01) to 467 +/- 101 dyne.sec.cm-5 1 mo after surgery (p < 0.05). This study
      demonstrates that transjugular portosystemic shunting rapidly and significantly
      worsens the hyperdynamic circulatory state of the cirrhotic patient. Although
      apparently noninvasive, this procedure should be considered with caution in
      cirrhotic patients with limited cardiac reserve.

PMID- 8276349
TI  - Hepatitis C virus genotypes: an investigation of type-specific differences in
      geographic origin and disease.
AB  - Because of the nucleotide sequence diversity of different isolates of hepatitis C
      virus, it has become important to clarify whether distinct genotypes of hepatitis
      C virus vary with respect to pathogenicity, infectivity, response to antiviral
      therapy and geographic clustering. We assessed nucleotide sequence variability in
      the 5' noncoding region of hepatitis C virus, using restriction enzymes to
      analyze the distribution of hepatitis C virus genotypes, in 80 patients with
      chronic hepatitis C virus infection. Genotypes were correlated with demographic,
      clinical and histological features. Thirty-seven patients were infected with type
      1, 10 had type 2 and 8 had type 3, and another 23 were infected with a new
      distinct hepatitis C virus type now classified as type 4. Two were infected with
      variants whose classification are uncertain. Types 1, 2 and 3 were found in
      patients from the United Kingdom, southern Europe, Asia, Africa and South
      America. Nineteen of 23 type 4 genotype isolates were from Middle Eastern
      patients, compared with 0 of 37 type 1 isolates (p < 0.001). Of 21 Middle Eastern
      patients, 19 (90.4%) had type 4 hepatitis C virus (p = 0.001, odds ratio = 9). We
      found no significant difference between the mean ages or mean serum
      aminotransferase concentrations between the various types. Types 1, 2, 3 and 4
      were found in patients with mild-to-moderate disease or severe disease. However,
      21 of 29 (72.4%) patients with type 1 who underwent liver biopsy had severe
      chronic hepatitis, cirrhosis or hepatocellular carcinoma histologically; 8 had
      mild or moderate chronic hepatitis without cirrhosis (p = 0.03, odds ratio =
      2.6).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276350
TI  - Combination of extracorporeal shock-wave lithotripsy and dissolution of
      gallbladder stones with methyl tert-butyl ether: a randomized study.
AB  - We conducted a prospective randomized study in gallstone patients to determine
      whether a combination of extracorporeal shock-wave lithotripsy and subsequent
      dissolution with methyl tert-butyl ether increases the success rate of methyl
      tert-butyl ether dissolution and shortens treatment time compared with
      monotherapy with methyl tert-butyl ether. Fifty patients were randomized into two
      groups. Twenty-five patients underwent extracorporeal shock-wave lithotripsy
      before contact dissolution with methyl tert-butyl ether, and 25 patients were
      treated with methyl tert-butyl ether alone. All patients had at least three
      stones or stones larger than 30 mm that were radiolucent on x-ray and had
      densities of less than 140 Hounsfield Units (HU) on computed tomography. Overall,
      the combined approach neither shortened the treatment time significantly vs.
      monotherapy with methyl tert-butyl ether nor reduced the time of hospitalization.
      The success rate was slightly but not significantly increased compared with that
      of methyl tert-butyl ether therapy alone. The recurrence rate was similar in the
      two groups after a median follow-up of 1 yr. However, when subgroups of patients
      with at least one stone larger than 15 mm or with stones with densities of more
      than 60 HU were analyzed, the clearance rate after 5 mo was significantly higher
      (p < 0.005 and p < 0.025, respectively) in patients subjected to a combination of
      extracorporeal shock-wave lithotripsy and methyl tert-butyl ether dissolution.
      Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether did not expose
      patients to more adverse effects than did treatment with methyl tert-butyl ether
      alone.

PMID- 8276351
TI  - Effect of ursodeoxycholic acid on intracellular pH in a bile duct epithelium-like
      cell line.
AB  - Recent studies in perfused livers and isolated hepatocytes indicate that
      ursodeoxycholic acid-induced HCO3-rich hypercholeresis originates at the
      ductule/duct level. The bile duct epithelium may be involved in bile
      alkalinization by passively reabsorbing the protonated unconjugated
      ursodeoxycholic acid, by directly secreting in response to an ursodeoxycholic
      acid-induced increase in acid/base transporter activity or by taking up UDCA- in
      exchange for a base equivalent. To investigate these processes in more detail, we
      studied the effects of ursodeoxycholic acid on intracellular pH in SK-ChA-1, a
      well-differentiated human cholangiocarcinoma cell line similar to bile duct
      epithelium in terms of intracellular pH regulatory mechanisms and morphological
      markers. Intracellular pH changes were monitored with a microfluorimetric setup
      using the fluorescent indicator 2'-7'-bis(2-carboxyethyl)-5,6,carboxy
      fluorescein. Administration of 50 to 1,000 mumol/L UDCA in the absence of HCO3
      caused dose-dependent intracellular acidification (intracellular pH = -0.13 +/-
      0.03 pH/U after 500 mumol/L ursodeoxycholic acid). Acidification was not
      prevented by preincubation of cells with 0.5 mmol/L 4,4-diisothiocyanatostilbene
      2,2,-disulfonic acid (DIDS) for 30 min or by furosemide administration (1
      mmol/L), thus ruling out the stimulation of Cl/HCO3 exchange or the presence of
      an ursodeoxycholic acid/base exchange. Ursodeoxycholic acid also acidified human
      fibroblasts, a cell type with no transport capability for ursodeoxycholic acid.
      In addition, direct measurement of the activities of the three major acid/base
      transporters in Sk-ChA-1 cells (Na+/H+ exchange, sodium-dependent and sodium
      independent Cl/HCO3 exchange) failed to show significative differences between
      cells treated with 500 mumol/L UDCA and controls.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8276352
TI  - Vasoactive effect of endothelin-1 on rat liver in vivo.
AB  - The purpose of this study was to evaluate the role of endothelin-1 in modulating
      hepatic microcirculation and liver damage. Rats were infused with endothelin-1 at
      doses ranging from 30 to 1,000 pmol/kg over 1 min through an indwelling cannula
      placed in the portal vein. In control rats, saline solution was infused at the
      same rate. Alterations in hepatic microcirculation were measured with an in vivo
      microscopy system. Serum lactate dehydrogenase activity, an indicator of hepatic
      damage, was measured 1 hr after endothelin-1 infusion. Immediately after infusion
      of endothelin-1, we noted a rapid increase in portal pressure, which remained
      increased for up to 30 min after endothelin-1 infusion. In contrast, systemic
      blood pressure remained unchanged, even at 1,000 pmol/kg of endothelin-1.
      Sinusoidal width was reduced and sinusoidal erythrocyte velocity was diminished
      in a dose-dependent manner. Oxygen saturation of blood in sinusoids was decreased
      in a dose-dependent manner, reaching values around 40% of control with 1,000
      pmol/kg endothelin-1. The degree of decrease in oxygen saturation of blood in
      sinusoids had an excellent correlation with the calculated blood flow in the
      liver tissue. Serum lactate dehydrogenase levels were three to four times control
      values when endothelin-1 was administered at 1,000 pmol/kg. Thus endothelin-1
      decreased hepatic tissue oxygenation associated with sinusoidal vasoconstriction.
      At high concentrations of endothelin-1, this decrease results in hepatocellular
      damage.

PMID- 8276353
TI  - Disulfide bond formation between dimeric immunoglobulin A and the polymeric
      immunoglobulin receptor during hepatic transcytosis.
AB  - The polymeric immunoglobulin receptor on rat hepatocytes binds dimeric IgA on the
      sinusoidal surface and mediates its transport to the canaliculus, where the
      complex of dimeric IgA and secretory component, the cleaved extracellular domain
      of polymeric immunoglobulin receptor, is secreted into bile. This process is
      unique in that disulfide bonds are formed between dimeric IgA and polymeric
      immunoglobulin receptor during transcytosis, permanently preventing their
      dissociation. Here we present three lines of evidence that disulfide bonding
      between dimeric IgA and polymeric immunoglobulin receptor occurs predominantly in
      a late transcytotic compartment and that hepatic transcytosis can proceed in the
      absence of disulfide bond formation. First, throughout the course of transcytosis
      the percentage of intracellular dimeric IgA disulfide bonded to polymeric
      immunoglobulin receptor is less than half that in bile, suggesting that disulfide
      bond formation is a late event in transcytosis. Second, dimeric IgA that recycles
      from early endocytotic compartments into the circulation is mostly noncovalently
      bound to secretory component. Finally, the rate of transcytosis of dimeric IgA
      and its appearance in bile are not affected when disulfide bond formation with
      polymeric immunoglobulin receptor is inhibited by blocking of free thiol groups
      on dimeric IgA with iodoacetamide. These results are consistent with other
      findings in the literature and indicate that the main physiological role of
      disulfide bond formation between dimeric IgA and polymeric immunoglobulin
      receptor is not to facilitate transcytosis but, rather, to stabilize the dimeric
      IgA-secretory component complex after its release into external secretions such
      as bile and intestinal secretions.

PMID- 8276354
TI  - An in vitro model of ethanol-dependent liver cell injury.
AB  - Primary cultures of adult rat hepatocytes were incubated (6 to 96 hr) with 50 to
      150 mmol/L ethanol, 0.5 mmol/L linoleate, 0.5 mmol/L palmitate, 0.5 mmol/L 4
      methylpyrazole, 0 to 25 mumol/L vitamin E phosphate or selected combinations of
      these agents. Agent-dependent changes in liver cell viability (AST release and
      reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and
      function (phospholipid peroxidation, hydrolysis, biosynthesis and triacylglycerol
      biosynthesis) were determined. The influence of ethanol on liver cell function
      and viability was dose and incubation time dependent. Short periods (24 hr or
      less) of exposure to 100 mmol/L ethanol increased liver cell triacylglycerol
      biosynthesis and phospholipid hydrolysis, peroxidation and biosynthesis without
      altering cell viability. However, longer periods (72 hr or more) of exposure to
      100 or 150 mmol/L ethanol resulted in significant reductions (30% to 50%) in cell
      viability, function and phosphatidylcholine biosynthesis and content. The ethanol
      dependent decreases in cell function and viability were potentiated by linoleate
      and reduced by vitamin E phosphate, palmitate and 4-methylpyrazole. These results
      suggest that ethanol-induced liver cell injury in vitro is not a result of
      ethanol per se, but factors such as acetaldehyde or oxyradicals produced as a
      consequence of ethanol metabolism. Therefore the incubation of cultured
      hepatocytes with ethanol may be an appropriate model in vitro for determining the
      mechanisms by which ethanol intake disrupts liver cell function in vivo.

PMID- 8276355
TI  - Vitamin A deficiency potentiates carbon tetrachloride-induced liver fibrosis in
      rats.
AB  - Earlier studies have shown that retinoid administration suppresses the generation
      of hepatic fibrosis and stimulates its regression in normal (i.e., vitamin A
      sufficient) carbon tetrachloride-treated rats. This study focuses on the possible
      role of a marginal or deficient vitamin A status on carbon tetrachloride-induced
      fibrosis. This experimental study in rats shows that vitamin A status, reflected
      by hepatic retinoid content (retinol and retinyl esters), modulates the
      development of hepatic fibrosis induced by carbon tetrachloride. In rats with low
      hepatic retinoid levels (12 +/- 0.9 micrograms/gm liver), carbon tetrachloride
      induced liver fibrosis was more pronounced than in rats with sufficient hepatic
      retinoid levels (1,065 +/- 327 micrograms/gm liver). Enhanced liver fibrogenesis
      was confirmed both morphologically and by a higher hydroxyproline content of the
      liver. It was associated with a reduced liver weight and the development of
      parenchymal regeneration nodules. Furthermore, carbon tetrachloride treatment
      itself reduced the hepatic retinoid content in rats independently of the liver
      vitamin A status before treatment and increased serum retinol levels in vitamin A
      sufficient rats. The results show that the vitamin A status of the liver plays an
      important role in hepatic fibrogenesis. Low hepatic vitamin A levels, which can
      be the result not only of low dietary intake but also of interference with
      vitamin A metabolism by agents such as ethanol and carbon tetrachloride, may be a
      risk factor for the development of liver fibrosis. We suggest that retinoids
      modulate collagen synthesis and deposition irrespective of the degree of
      hepatocellular necrosis induced by carbon tetrachloride.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8276356
TI  - Hemodynamic changes after ligation of a major branch of the portal vein in rats:
      comparison with rats with portal vein constriction.
AB  - In chronic portal-hypertensive rat models, such as portal vein constriction or
      cirrhosis, the portal blood flow that effectively perfuses the hepatocytes is
      substantially reduced because of anatomical or functional shunts. It is possible
      therefore that a feedback mechanism from the liver to the splanchnic bed is
      responsible for the splanchnic hyperemia observed in chronic portal hypertension.
      To investigate the possible role of such a feedback mechanism, we examined the
      chronological changes in both portal and systemic hemodynamics in rats after
      ligation of a major branch of the portal vein that supplies about 80% of the
      liver circulation. Rats submitted to sham surgery and portal vein-constricted
      rats were also studied. Blood flow and portal-systemic shunting were measured by
      radioactive microsphere techniques. For 7 days after portal-branch ligation,
      transient portal hypertension resulted from an elevated portal resistance.
      However, no significant changes in portal venous inflow or splanchnic arteriolar
      resistance were found in the portal branch-ligated rats, whereas in the portal
      vein-constricted rats significant hyperdynamic changes in these parameters were
      noted. On the other hand, transient hyperdynamic changes occurred in the systemic
      circulation during the period from the fourth to the sixth day after portal
      branch ligation, similar to those observed in the portal vein-constricted rats.
      The lack of hyperdynamic changes in the portal territory of the portal branch
      ligated rats suggests that the splanchnic hyperemia found in chronic portal
      hypertensive states is unlikely to be caused by a feedback mechanism from the
      ischemic hepatic parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276358
TI  - Cytokine stimulation of nitric oxide formation and differential regulation in
      hepatocytes and nonparenchymal cells of endotoxemic rats.
AB  - Some disease processes in which increased endotoxin and cytokine levels exist
      (e.g., sepsis and infantile diarrhea) are also associated with increased levels
      of blood nitrates, the stable end products of nitric oxide. Available evidence
      suggests that the effects of an endotoxic environment, with its attendant complex
      cytokine networks, on liver function are mediated in part by modulation of
      hepatic nitric oxide synthesis. This hypothesis was tested by means of studying
      nitric oxide formation and its regulation in liver parenchymal and nonparenchymal
      cells of rats that had been continuously infused with endotoxin for 30 hr.
      Hepatocytes of such rats responded to in vitro stimulation for 20 hr by single
      cytokines, tumor necrosis factor, interleukin-1 beta and interferon-gamma with
      enhanced nitric oxide formation. In combination, interferon-gamma and endotoxin
      had greater synergistic effect on hepatocytes than did tumor necrosis factor and
      endotoxin. Kupffer cells of these endotoxic rats responded to 20 hr of interferon
      gamma stimulation with the same enhanced nitric oxide formation we documented
      previously for endotoxin. Potentiation of the effect, through combination of
      endotoxin and interferon-gamma, was not as marked as it was with hepatocytes.
      Challenge of Kupffer cells with tumor necrosis factor or interleukin-1 beta
      evoked no response. Hepatocytes and Kupffer cells of time-matched, saline
      solution-treated rats were unresponsive to endotoxin or cytokine stimulation.
      Small quantities of nitric oxide were produced by endothelial cells
      spontaneously; this production was somewhat enhanced in cells of the endotoxin
      infused rats by a 20-hr in vitro endotoxin challenge. Studies with inhibitors
      suggest that enhanced nitric oxide formation by endotoxic hepatocytes and Kupffer
      cells in response to in vitro endotoxin stimulation is differentially regulated.
      Our findings indicate modulation of nitric oxide generation by cytokines in vitro
      in various liver cell types of endotoxic rats. A similar scenario may exist in
      vivo because of the prevailing inflammatory response to endotoxin administration.

PMID- 8276357
TI  - Small-for-size liver transplanted into larger recipient: a model of hepatic
      regeneration.
AB  - Orthotopic liver transplantation was performed in 60 recipient rats weighing 200
      to 250 gm. Sixty rats of the same strain were used as liver donors, 30 weighing
      100 to 140 gm (small for size) and the other 30 weighing 200 to 250 gm (same
      size). After 1, 2, 3, 4, 7 and 14 days (n = 5 each) DNA synthesis, nuclear
      thymidine labeling and mitoses were increased in both the small-for-size and same
      size groups, but significantly more in the former. These changes were maximal
      after 48 to 72 hr, similar to but later than the well-known regeneration response
      after partial hepatectomy, which peaks at 24 hr in rats. Indirect indexes of
      regeneration of the transplanted livers also were measured: plasma or serum
      ornithine decarboxylase; insulin and glucagon serum levels; estradiol and
      testosterone serum levels (and their nuclear and cytosolic receptors); and
      transforming growth factor-beta, c-Ha-ras and c-jun mRNA expressions. With the
      small-for-size transplantation, these followed the same delayed pattern as the
      direct regeneration parameters. The small livers gradually increased in size over
      the course of 1 to 2 wk and achieved a volume equal to that of the liver
      originally present in the recipient. In contrast, no significant liver weight
      gain occurred in the transplanted livers from same-size donors despite the
      evidence of regeneration by direct indexes, but not by most of the surrogate
      parameters, including ornithine decarboxylase.

PMID- 8276359
TI  - Salicylamide sulfate cell entry in perfused rat liver: a multiple-indicator
      dilution study.
AB  - The hepatocellular entry of salicylamide sulfate conjugate, which binds to both
      red blood cells and albumin, was examined with the multiple-indicator dilution
      technique in the perfused rat liver, with medium containing both 20% red cells
      and 1% albumin (set A), red cells only (set B), albumin only (set C) and neither
      red cells nor albumin (set D). [14C]Salicylamide sulfate, 51Cr-labeled red cells
      (a vascular reference), 125I-labeled albumin, [3H]sucrose or [58Co]
      ethylenediaminetetraacetic acid (EDTA) (high and low molecular weight
      interstitial references, respectively) and 3H2O or D2O (a cellular reference)
      were injected as a bolus into the portal vein. Among all sets of outflow data,
      the earliest immediate vascular recoveries for the [14C] salicylamide sulfate
      were lower than those for the vascular reference. For sets A and B, the upslopes
      precessed those for the 58Co-EDTA curve, then crossed over the 58Co-EDTA curves,
      with lower magnitude peaks occurring at the same time as those for labeled
      albumin, whereas for sets C and D, in which red cells were absent, the upslopes
      of [14C]salicylamide sulfate lagged behind those for labeled albumin and
      [3H]sucrose, reaching lower magnitude peaks coincidental in time with those for
      labeled sucrose. The precession of the [14C]salicylamide sulfate curve over 58Co
      EDTA or [3H]sucrose in the presence (sets A and B) but not in the absence (sets C
      and D) of red cells and the absence of precession with albumin alone (set C)
      suggest that a red cell effect on the upslope is more evident than that for
      albumin. For all experiments, the downslopes of the sulfate curve crossed over
      those of the labeled red cells, albumin, 58Co-EDTA and sucrose curves and then
      the water curve at around the peak. The downslopes of the [14C]salicylamide
      sulfate were similar to those for labeled water, suggesting rapid cellular influx
      and efflux of salicylamide sulfate. Quantitative evaluation with a barrier
      limited space-variable transit-time model for rapidly equilibrating red cell and
      albumin binding accounted for the upslope effects on [14C]salicylamide sulfate
      behavior and demonstrated its relatively high liver cell permeability. Values for
      the unbound permeability surface area product (0.029 to 0.036 ml sec-1.gm-1) were
      not different, regardless of the presence or absence of red cells and albumin,
      and slightly exceeded values for hepatic blood flow (0.0186 +/- 0.0016 ml sec
      1.gm-1). Comparable influx (0.083 to 0.14 sec-1) and efflux (0.10 to 0.18 sec-1)
      coefficients were obtained, suggesting rapid cellular entry and efflux of
      salicylamide sulfate.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8276360
TI  - The hepatitis B virus preS2/St transactivator utilizes AP-1 and other
      transcription factors for transactivation.
AB  - Integrated hepatitis B virus DNA cloned from hepatitis B virus-associated
      hepatocellular carcinoma frequently contains 3'-truncated middle surface genes
      (preS2/St), which were recently found to have a transcriptional transactivator
      function. Because preS2/St, among others, is able to transactivate the promoters
      of the cellular oncogenes c-myc and c-fos, it has been speculated that integrated
      preS2/St genes might contribute to hepatitis B virus-associated liver
      carcinogenesis. In this study, we investigated the mechanism of target gene
      stimulation by preS2/St. It was found that deletion of a fragment containing the
      binding site for transcription factor AP-1 (Jun-Fos) substantially decreases
      inducibility of the human c-myc promoter by preS2/St. A subsequent investigation
      of AP-1 activation by preS2/St revealed the following: (a) insertion of
      multimeric AP-1 binding sites confers inducibility to an otherwise unstimulatable
      test promoter; (b) transactivation of AP-1 sites is dramatically increased when
      Jun and Fos are overexpressed by cotransfected expression plasmids; and (c)
      inhibitors of AP-1 activation also impair transactivation by preS2/St. Besides AP
      1, preS2/St was also able to utilize the unrelated transcription factors NF-kappa
      B and AP-2 for transactivation, suggesting that the gene product of preS2/St acts
      indirectly through one or several general cellular pathways rather than as a bona
      fide transcription factor. Because AP-1 conveys induction of a large panel of
      tumor-relevant genes, its preS2/St-dependent activation implies a possible
      causative role in hepatitis B virus-associated hepatocarcinogenesis.

PMID- 8276361
TI  - Hepatitis B infection and liver transplantation: the art of the possible.

PMID- 8276362
TI  - Benzodiazepine-receptor ligands and hepatic encephalopathy: a causal
      relationship?

PMID- 8276363
TI  - Does hepatitis C virus cause hepatocellular carcinoma?

PMID- 8276364
TI  - What's wrong when it isn't right: situs inversus and genetic control of organ
      position.

PMID- 8276365
TI  - Creatine kinase BB: a response marker in liver and other organs.

PMID- 8276366
TI  - Flumazenil in cirrhotic patients in hepatic coma: a randomized double-blind
      placebo-controlled crossover trial.
AB  - Previous reports have suggested that "endogenous" benzodiazepines could
      contribute to neural inhibition in hepatic encephalopathy. RO 15-1788
      (flumazenil), a specific antagonist of brain benzodiazepine receptors, could thus
      reverse the neurological symptoms of hepatic encephalopathy. To test this
      possibility, we conducted a double-blind, placebo-controlled crossover trial of
      the efficacy of flumazenil in cirrhotic patients in hepatic coma. Seventy-seven
      cirrhotic patients in hepatic coma were evaluated. Fifty-six were excluded from
      the trial because of multiorgan failure or because coma was precipitated by prior
      use of benzodiazepines, and 21 patients were randomly assigned to the flumazenil
      group (11 patients) or the placebo group (10 patients). Treatment was
      administered intravenously as a 20-ml solution (placebo or 2 mg flumazenil);
      seven patients were crossed over. Clinical status was assessed blindly by two
      observers, using a modified Glasgow scale, every 15 min for 6 hr.
      Electroencephalogram tracings obtained before and after drug administration were
      evaluated blindly by two independent observers. Serum concentrations of
      benzodiazepines before treatment were measured by means of a fluorescence
      polarization immunoassay. Improvement in neurological symptoms was observed in
      six patients treated with flumazenil, whereas none in the placebo group showed
      improvement (p < 0.05; Fisher's exact test). Improvements in electroencephalogram
      tracings were demonstrated in four patients treated with flumazenil, compared
      with two patients in the placebo group (p = NS). Benzodiazepines were found in
      the serum of four patients treated with flumazenil (two responders and two
      nonresponders); all of these patients had received pharmaceutical benzodiazepines
      4 to 6 days before the trial.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276367
TI  - Reduction of gastric hyperemia by glypressin and vasopressin administration in
      cirrhotic patients with portal hypertensive gastropathy.
AB  - Gastric mucosal perfusion is increased in portal-hypertensive gastropathy, and
      this may contribute to gastric bleeding from these lesions. Therefore drugs
      reducing gastric mucosal perfusion may be beneficial in the treatment of overt
      bleeding from portal-hypertensive gastropathy. In this study gastric mucosal
      perfusion was assessed in 28 cirrhotic patients with portal-hypertensive
      gastropathy under basal conditions and after double-blind intravenous
      administration of vasopressin (0.4 U/min), glypressin (2-mg injection) or
      placebo, with laser-Doppler flowmetry and reflectance spectrophotometry.
      Vasopressin and glypressin induced a significant increase in blood pressure and a
      decrease in heart rate. These effects were more pronounced in the vasopressin
      group. Both vasopressin and glypressin induced a sustained and similar reduction
      in gastric mucosal perfusion as assessed by laser-Doppler flowmetry (-36% +/- 8%
      and -34% +/- 6%, respectively; p < 0.05 with respect to basal values and with
      respect to the control group), whereas placebo had no effect. Both drugs
      significantly reduced the oxygen content of the gastric mucosa; however, the
      impairment in mucosal oxygenation was greater (p < 0.05) in the vasopressin group
      (-17% +/- 3%) than in the glypressin group (-6% +/- 0.1%). We conclude that the
      increased gastric perfusion in cirrhotic patients with portal-hypertensive
      gastropathy may be reduced by either vasopressin or glypressin. These findings
      support the use of these drugs in clinical trials treating bleeding portal
      hypertensive gastropathy. The lower reduction in gastric mucosal oxygen content
      observed with glypressin could decrease the incidence of ischemic adverse events
      associated with the use of vasopressin.

PMID- 8276368
TI  - Pretransplantation interferon treatment and recurrence of hepatitis B virus
      infection after liver transplantation for hepatitis B-related end-stage liver
      disease.
AB  - Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis
      is commonly complicated by reinfection with the hepatitis B virus, with rapidly
      progressive liver disease and poor survival rate. We assessed the efficacy of
      prior therapy with recombinant interferon-alpha on the prevention of
      posttransplantation hepatitis B virus reinfection. Twenty-two patients with
      hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU
      (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha
      until transplantation. The rates of posttransplantation hepatitis B virus
      reinfection and survival in this group were compared with those in a group of 26
      patients previously given transplants for the same disease but not given
      interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis
      was applied after transplantation in both groups. Recombinant interferon-alpha
      was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with
      disappearance of serum hepatitis B virus DNA in seven of the eight patients
      initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of
      the three patients initially positive for HBeAg. Serum hepatitis B virus DNA
      remained detectable with polymerase chain reaction at transplantation in 56% of
      the interferon-treated patients. After transplantation, hepatitis B virus
      reinfection was more frequent in polymerase chain reaction-positive than in
      polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One
      patient's condition deteriorated during interferon treatment; this patient was
      not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared
      from serum) improved so markedly during treatment that they were not given
      transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276369
TI  - Gastrointestinal transit in cirrhotic patients: effect of hepatic encephalopathy
      and its treatment.
AB  - Chronic hepatic encephalopathy is highly responsive to changes in diet, to
      antibiotic therapy and to ingestion of nondigestible disaccharides. The precise
      pathophysiology of chronic hepatic encephalopathy in individual cases is highly
      variable, although ammonia toxicity and production of neurotransmitterlike
      substances in the gut have been proposed to contribute to the overall syndrome of
      chronic hepatic encephalopathy. The support for this hypothesis is based on the
      empiric observation that reduction in protein intake, a catharsis or both are
      effective treatments for chronic hepatic encephalopathy. This study was performed
      to evaluate the effect of mild subclinical and low-grade (grade 0 to 1) chronic
      hepatic encephalopathy on gastric emptying and oral-cecal transit times. Thirty
      patients were studied. Ten had no evidence of chronic hepatic encephalopathy, as
      determined with a battery of neuropsychiatric studies (group 1); 10 had
      subclinical hepatic encephalopathy, as judged on the basis of abnormal
      neuropsychiatric test performance but normal neurological examination (group 2);
      and 10 had grade 1 hepatic encephalopathy. Each underwent a liquid gastric
      emptying study and a lactulose oral-cecal transit time study. No significant
      differences between groups were evident in the results of the gastric emptying
      studies. In contrast, the time required for a lactulose load to reach the cecum
      was significantly greater in the patients with hepatic encephalopathy (p < 0.01)
      and increased as a function of the hepatic encephalopathy grade.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276370
TI  - Randomized clinical study of the efficacy of amiloride and potassium canrenoate
      in nonazotemic cirrhotic patients with ascites.
AB  - Although some clinical studies seem to prove the efficacy of nonantialdosteronic
      potassium-sparing diuretics in the treatment of ascites, no controlled study has
      compared the efficacy of these drugs with that of antialdosteronic diuretics.
      Forty nonazotemic cirrhotic patients were randomized to receive amiloride (group
      A, n = 20) or potassium canrenoate (group B, n = 20). The initial doses of
      amiloride and potassium canrenoate were 20 mg and 150 mg, respectively. The doses
      were increased in stepwise fashion to 60 and 500 mg/day, respectively, if no
      response ensued. Nonresponders to the highest doses of each drug were later
      treated with potassium canrenoate and amiloride, respectively. Seven of 20 group
      A patients responded to amiloride, whereas 14 of 20 group B patients responded to
      potassium canrenoate (p < 0.025). Seven of 13 nonresponders to amiloride later
      responded to potassium canrenoate, whereas only two of the nonresponders to
      potassium canrenoate later responded to amiloride. The diuretic responses to
      amiloride and potassium canrenoate were related to the activity of the renin
      aldosterone system. All responders to amiloride (n = 9) had normal values of
      plasma aldosterone. All nonresponders to amiloride who later responded to
      potassium canrenoate (n = 7) had increased levels of plasma aldosterone.
      Moreover, on comparison of all responders (n = 21) and nonresponders (n = 12) to
      potassium canrenoate, a higher degree of renal proximal sodium reabsorption (with
      consequent limitation of sodium delivery to the distal tubule) was found to be
      the main difference.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276371
TI  - Cerebral hemodynamic and metabolic changes in fulminant hepatic failure: a
      retrospective study.
AB  - The purpose of this retrospective study was to determine cerebral hemodynamic and
      metabolic changes in comatose patients with fulminant hepatic failure.
      Computerized tomography of the brain and cerebral blood flow measurements by the
      xenon-computerized tomography scan or intravenous xenon-133 methods were obtained
      in 33 patients with fulminant hepatic failure. In a subgroup of 22 patients,
      arteriojugular venous oxygen content difference and cerebral metabolic rate for
      oxygen were determined. Carbon dioxide reactivity was tested in 17 patients, and
      intracranial pressure was recorded by an epidural monitor in 8 patients. Cerebral
      blood flow and arteriojugular venous oxygen content difference were adjusted to
      the average arterial carbon dioxide pressure of the sample (32 mm Hg). Adjusted
      cerebral blood flow varied from 16.5 to 94.7 ml/100 gm/min; 52% of the patients
      had reduced adjusted cerebral blood flows (less than 33 ml/100 gm/min), whereas
      24% had hyperemic values (greater than 50 ml/100 gm/min). Patients with higher
      adjusted cerebral blood flows showed cerebral swelling on computerized tomography
      scan (p < 0.002), were in deeper coma (p < 0.05) and had greater mortality (p <
      0.002). The adjusted arteriojugular venous oxygen content difference was
      negatively correlated with adjusted cerebral blood flow (r = -0.61, p < 0.002).
      The majority of patients with reduced adjusted cerebral blood flows had low
      adjusted arteriojugular venous oxygen content differences (less than 5 vol%),
      indicating hyperemia rather than ischemia. The average cerebral metabolic rate
      for oxygen was 50% of normal (1.6 +/- 0.4 ml/100 gm/min); even patients with low
      cerebral metabolic rates for oxygen recovered neurologically.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8276372
TI  - c-met mRNA overexpression in human hepatocellular carcinoma.
AB  - This study was aimed at assessing the presence of c-met overexpression in human
      hepatocellular carcinoma and at determining whether this feature is associated
      with a definite clinical or pathological characteristic. Expression of c-met was
      determined by Northern-blot hybridization of a specific probe (human met proto
      oncogene) in 18 tumoral and nontumoral liver samples obtained in 18 cirrhotic
      patients with hepatocellular carcinoma submitted to surgical treatment. Eight of
      the 18 hepatocellular carcinomas exhibited c-met overexpression, with an increase
      ranging between 2-fold and 10-fold when compared by densitometry with the
      surrounding liver. By contrast, in the remaining 10 cases c-met expression was
      almost identical to that of the surrounding nontumoral liver tissue.
      Overexpression of c-met was not related to either the age, sex, etiology or
      functional status of the underlying liver disease, or to the size of the tumor,
      to its differentiation degree or to the presence of pseudocapsule invasion and
      existence of additional neoplastic nodules. These data indicate that almost half
      of the human hepatocellular carcinomas exhibit c-met overexpression.
      Nevertheless, the biological relevance of this characteristic is not known.

PMID- 8276373
TI  - Androgen receptor in human liver: characterization and quantitation in normal and
      diseased liver.
AB  - Liver is responsive to sex hormones. The role of androgens in normal human liver
      function is not well understood, although androgens have been implicated in
      several liver diseases. Because the human hepatic androgen receptor has not been
      adequately characterized, we analyzed cytosolic and nuclear fractions from normal
      human liver of both sexes for androgen-binding activity using multipoint
      saturation analysis with the androgenic radioligand methyltrienelone (R1881).
      Both cytosolic and nuclear fractions of both sexes displayed high affinity R1881
      binding (dissociation constants = nanomolar range). The R1881 binding in both
      fractions is highly specific in that potent androgens compete well, and the
      antiandrogens hydroxyflutamide and cyproterone acetate show partial competition;
      other nonandrogenic steroid hormones do not compete. The cytosolic R1881 receptor
      displays physicochemical characteristics of androgen receptors in other tissues
      in that it is retained by heparin-Sepharose and by DNA cellulose after
      activation, and it displays a molybdate-stabilized 8S form on sucrose gradients
      and a 7.3-nm species on gel filtration chromatography. Receptor activity was also
      quantitated in specimens of hepatic adenoma, focal nodular hyperplasia and
      metastatic carcinoma to the liver and in samples of adjacent histologically
      normal specimens when available. In general, both the diseased and normal
      portions of the livers from the patients with hepatic adenoma and metastatic
      carcinoma to the liver, but not focal nodular hyperplasia, demonstrated reduced
      total androgen-receptor activity as compared with liver from normal
      individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276374
TI  - Immunodetection of the p21-ras products in human normal and preneoplastic tissues
      and solid tumors: a review.
AB  - Immunohistochemical detection of p21-ras to identify and characterize
      preneoplastic or neoplastic lesions in human tissues is reviewed. Information
      concerning the commercially available antibodies is presented. Antibodies DWP,
      Ras-10, Y13-259, YA6-172, NCC-001, and NCC-004 are fully documented with respect
      to their behavior in appropriate specificity tests and appear to be reliable
      reagents. After reviewing the data we have identified three groups of tissues or
      organs with respect to positive immunostaining for p21-ras as the significant
      criterion of malignancy. These three groups comprise (1) tissues for which no
      definite conclusion could be drawn (colon, lung, bladder, ovary, and neural and
      odontogenic tissues) despite occasional claims to the contrary, (2) tissues for
      which conclusions were negative (pancreas and stomach), and (3) tissues for which
      p21-ras staining positively discriminated malignant from normal tissues (liver,
      uterus, and salivary gland). Immunohistochemically detectable levels of products
      from a mutated ras gene could be demonstrated in a fraction of the samples from
      colon, lung, and bladder carcinomas, as well as in some histologically normal
      tissues adjacent to a colon carcinoma. The possibility that a higher relative
      intensity of the immunostaining reaction for p21-ras might discriminate malignant
      tissues from normal tissues or benign lesions in breast, pancreas, stomach, lung,
      uterus, or thyroid samples is suggested. Further studies now appear warranted and
      a strategy is proposed to validate the conclusions reached thus far.

PMID- 8276375
TI  - Evaluation of surgically excised mitral valves: revised recommendations based on
      changing operative procedures in the 1990s.
AB  - In 1990, 95 mitral valves from 54 women and 41 men (mean age, 61 years; age
      range, 8 to 85 years) were replaced (76%) or repaired (24%) at the Mayo Clinic.
      Functionally, 58% of the valves were purely regurgitant (MR), 25% were stenotic
      and regurgitant (MS-MR), and 17% were purely stenotic (MS). Postinflammatory
      (presumably rheumatic) disease accounted for 100% of MS cases, 92% of MS-MR
      cases, and 16% of MR cases. Other causes of pure MR included floppy valves (49%),
      ischemic heart disease (13%), infective endocarditis (9%), miscellaneous (9%),
      and indeterminate (4%). Thus, postinflammatory disease represented the major
      cause of both mitral stenosis (MS and MS-MR) and overall mitral valve disease in
      our surgical population. In contrast, floppy valves were the most commonly
      observed cause of pure MR. Among postinflammatory valves, 55% were completely
      excised and 45% had only the anterior leaflet removed; all were replaced. In
      contrast, floppy valves were incompletely excised in 96%; 67% were repaired and
      only 33% were replaced. Because mitral valves frequently are incompletely
      excised, rendering an accurate etiologic diagnosis requires not only a
      morphologic assessment of resected tissues but also a knowledge of the clinical
      history, operative details, and functional state of the valve.

PMID- 8276376
TI  - Localization of hyaluronan in normal breast tissue, radial scar, and tubular
      breast carcinoma.
AB  - Hyaluronan (hyaluronic acid [HYA]) is one of the extracellular matrix components
      involved in normal cell physiology and is localized mainly in bodily fluids and
      connective tissues. Increased amounts of HYA in serum have been demonstrated in a
      number of neoplastic and inflammatory conditions, among them breast cancer.
      Tubular breast carcinoma (TC) and radial scar (RS) are two breast lesions that
      microscopically display characteristic stromal alterations and possess gross and
      microscopic similarities. Due to the importance of HYA as a component of the
      extracellular matrix, we investigated its presence in these lesions and in normal
      breast tissue. Using a biotinylated HYA-binding region for the in situ detection
      of HYA, we noted an increased amount of HYA in both TC and RS as compared with
      that in normal breast tissue specimens. A strong reactivity was observed
      predominantly around glandular structures and in the interlobular stroma of both
      TC and RS. Perivascular HYA staining also was distinctly observed in these
      lesions (TC and RS). Some HYA was observed in the connective tissue of the
      intralobular regions, around small blood vessels, and in the perivascular
      connective tissue of the normal breast. The distribution of HYA adjacent to the
      epithelium in the normal breast suggests a role for HYA in the interaction
      between epithelium and stroma of the normal breast. Its increase in the
      connective tissue of both TC and RS reflects the derangement of the stroma
      commonly observed in these conditions and supports the notion that these lesions
      may be associated.

PMID- 8276377
TI  - Undifferentiated spindle cell carcinoma of the gallbladder: a clinicopathologic,
      immunohistochemical, and flow cytometric study of 11 cases.
AB  - Eleven primary spindle cell carcinomas (SpCCs) of the gallbladder are reported.
      They occurred in eight women and three men ranging in age from 59 to 80 years
      (mean age, 66.5 years). Histologically, the tumors showed interlacing bundles of
      atypical spindle cells with eosinophilic cytoplasm, oval to elongated nuclei, and
      conspicuous nucleoli. Eight SpCCs contained tiny foci of neoplastic glands
      similar to those seen in adenocarcinoma, and two of these cases also had small
      foci of neoplastic squamous epithelium. A gradual transition between the squamous
      cell carcinoma and the spindle cell component was observed in one tumor.
      Immunohistochemically, all SpCCs were positive for at least one of the epithelial
      markers (epithelial membrane antigen, nine cases; AE1/AE3, nine cases;
      carcinoembryonic antigen, three cases; and EAB 903, one case), and the tumor
      cells also were immunoreactive to mesenchymal marker (vimentin, eight cases),
      muscle markers (alpha-smooth muscle actin, one case; desmin, one case), and
      histiocytic marker (HAM 56, one case). Abnormalities in tumor suppressor gene p53
      expression also were found in two of the 11 SpCC cases using monoclonal antibody
      PAb 1801. In six cases for which data were available flow cytometry revealed
      aneuploidy in three SpCCs (50%). The survival curve of the SpCC cases (mean
      survival, 9 months) was less favorable than that of 224 cases of adenocarcinoma
      of the gallbladder (mean survival, 81 months) (P = .0011). These results indicate
      that SpCC of the gallbladder is an epithelial tumor with sarcomatoid components
      and its prognosis is unfavorable.

PMID- 8276378
TI  - Epstein-Barr virus infection in liver transplantation patients: correlation of
      histopathology and semiquantitative Epstein-Barr virus-DNA recovery using
      polymerase chain reaction.
AB  - Epstein-Barr virus (EBV) infection may complicate orthotopic liver
      transplantation, and can lead to hepatitis with subsequent graft failure and to
      benign and malignant lymphoproliferative disorders. Early diagnosis allows for
      prevention or treatment of complications. Histopathologic features of EBV
      infection in the liver vary and may be difficult to recognize. To delineate the
      morphologic features that allow for recognition we studied 61 biopsy specimens
      from 37 patients, correlating the results of EBV-DNA demonstration after
      polymerase chain reaction with histopathology of formalin-fixed, hematoxylin
      eosin-stained liver biopsy specimens. DNA was extracted from fresh liver biopsy
      samples, and polymerase chain reaction was carried out with EBV primers (capsid
      protein gp220) using standard techniques and 25-cycle amplification. Epstein-Barr
      virus-related sequences after polymerase chain reaction were detected by DNA blot
      assay. Histopathologic features were classified into three categories on the
      basis of the semiobjective determination of the number and distribution of
      immunoblasts and other immature lymphocytes in portal tracts and sinusoids:
      highly suggestive (three biopsy specimens), indeterminant (one biopsy specimen),
      and negative (57 biopsy specimens). Only the three highly suggestive biopsy
      specimens had high levels of EBV-DNA. We conclude that the histopathologic
      features of EBV infection after orthotopic liver transplantation can be relied on
      to establish the diagnosis.

PMID- 8276379
TI  - Diffuse pulmonary lymphangiomatosis.
AB  - Angiomatous lesions of the lung are uncommon and not well characterized. We
      describe nine cases of a distinct lymphatic vascular lesion that we have termed
      "diffuse pulmonary lymphangiomatosis." Extrathoracic lymphangiomatous lesions
      were not identified. The patients comprised seven males and two females with a
      mean age at presentation of 10 years (age range, 1 month to 33 years). Six
      patients were younger than 10 years of age. Symptoms included "wheezing" or
      "asthma" (44%) and dyspnea (22%) present for 3 months to 20 years. Chest
      radiographs showed bilateral interstitial infiltrates, often greatest in the
      lower lobes. Pleural or pericardial effusions were present or developed in six
      patients. Pulmonary function tests showed in two patients and mixed obstruction
      and restriction in five patients. Open lung biopsies (nine patients) and autopsy
      (one patient) showed anastomosing endothelial lined spaces along pulmonary
      lymphatic routes (especially pleural and interlobular septal) accompanied by
      asymmetrically spaced bundles of spindle cells, which were prominent in six
      cases. Hemosiderin deposition often was present in the spindle cell areas and in
      the adjacent lung. The lining cells were positive for factor VIII-related antigen
      (eight cases) and Ulex europaeus I agglutinin (four cases). The spindle cells
      were reactive with antibodies to vimentin (nine cases), desmin (six cases), actin
      (seven cases), progesterone receptor (seven cases), and proliferating cell
      nuclear antigen (one case); they were negative for estrogen receptor (seven
      cases), keratin, (eight cases), and HMB-45 (eight cases). Diffuse pulmonary
      lymphangiomatosis was progressive in eight cases and was most aggressive in the
      youngest children. Two of the children have died, one of pulmonary hemorrhage and
      the other after heart-lung transplantation. Diffuse pulmonary lymphangiomatosis
      is distinct from lymphangiectasis, lymphangioleiomyomatosis, pulmonary capillary
      hemangiomatosis, Kaposi's sarcoma, and kaposiform hemangioendothelioma. Due to
      its distribution and histology, a lymphatic origin of the lesion is favored.

PMID- 8276380
TI  - New observations on the etiology of aortic valve disease: a surgical pathologic
      study of 236 cases from 1990.
AB  - Among 236 aortic valves surgically excised at the Mayo Clinic in 1990 (mean
      patient age, 66 years; age range, 10 to 92 years), 154 (65%) were stenotic, 58
      (25%) were insufficient, and 24 (10%) were both stenotic and insufficient. Pure
      stenosis was related to calcification, and causes included degenerative (51%),
      bicuspid (36%), post-inflammatory (9%), and other (4%) reasons. Fourteen (9%)
      valves with pure stenosis also underwent ventricular septal myectomy, 12 for
      hypertrophy and two for co-existent hypertrophic cardiomyopathy. Pure
      insufficiency was not related to calcification, and causes included aortic root
      dilatation (50%), bicuspid valve (14%), post-inflammatory (14%), post-therapeutic
      (14%), and other (8%) reasons. Combined stenosis and insufficiency was secondary
      to degenerative calcification (46%), bicuspid and post-inflammatory etiologies
      (17% each), post-therapeutic (13%), and indeterminate (8%) causes. New
      observations include the following findings: (1) degenerative (senile) disease is
      the most common cause of aortic stenosis and combined stenosis and insufficiency
      at the Mayo Clinic, (2) aortic root dilatation is the most common cause of pure
      aortic insufficiency, (3) post-therapeutic aortic valve disease now leads to
      valve replacement in a substantial percentage of patients, particularly among
      those with insufficiency, (4) post-inflammatory (presumably rheumatic) disease is
      relatively uncommon in all three functional categories, (5) septal myectomy may
      be performed for hypertrophic states other than hypertrophic cardiomyopathy, and
      (6) adults with operated congenital heart disease are undergoing valve
      replacement for annular dilatation with insufficiency. Because of the increasing
      age of the general population, the prominence of age-related degenerative aortic
      valve calcification and aortic root dilatation may have important implications
      concerning future health care costs.

PMID- 8276381
TI  - Osteofibrous dysplasia: clinicopathologic study of 80 cases.
AB  - A thorough review of the clinical, radiologic, and histologic features of 80
      cases of long bone osteofibrous dysplasia is presented. Of the six cases of
      osteofibrous dysplasia immunostained with a cytokeratin antibody, two were
      cytokeratin positive; however, the five cases of fibrous dysplasia that were
      stained were all negative. Follow-up (mean, 5.4 years; range, 1 month to 31
      years) data were available for 41 cases (51%). From the consultation series nine
      of the 18 patients studied had recurrences, regardless of the different treatment
      regimens. The average recurrence interval in these patients was 2.7 years. Two
      patients had incomplete excision and six had biopsy only. All eight of these
      patients had residual tumors. Among the 16 Mayo Clinic patients, one had
      recurrence 5 years after the initial treatment. In two cases, 7-year-old and 6
      year-old boys, histologic maturation to fibrous dysplasia was observed 4 and 10
      years later, respectively. Adamantinoma has not developed in any of the 41 cases
      of osteofibrous dysplasia for which we have follow-up information. It seems clear
      that osteofibrous dysplasia does not progress to adamantinoma. Our study suggests
      that osteofibrous dysplasia is probably a variant of fibrous dysplasia, as
      demonstrated by the maturation of two lesions of osteofibrous dysplasia to
      fibrous dysplasia. Surgical treatment may be appropriate in cases with an
      extensive lesion, pseudoarthrosis, and accentuated tibial bowing. The overall
      prognosis is good, even with recurrence.

PMID- 8276382
TI  - Prognostic value of cells with more than 5c DNA content in node-negative breast
      cancer as determined by image cytometry from tissue sections.
AB  - The aim of this investigation was to study the prognostic significance of 5c
      cells (presence of cancer cells with > 5c DNA content; ie, over 18 pg of DNA per
      nucleus) in axillary node-negative breast cancer. Tissue sections (3 microns)
      from 134 tumors were stained for DNA using the Feulgen method and screened for
      the percentage of 5c cells with the CAS 200 image analysis system (Cell Analysis
      System, Inc, Lombard, IL). Cancer cells with a DNA content exceeding the 5c level
      were found in 45% (60 of 134) of the cases, accounting for a median of 0.2%
      (range, 0.05% to 1.05%) of all cells. The presence of 5c cells was associated
      with a high histologic grade of the tumor (P = .0001), a large number of mitoses
      (P < .0001), flow cytometric DNA aneuploidy and high S-phase fraction (P = .0002
      and P < .0001, respectively), and c-erbB-2 oncoprotein and p53 tumor suppressor
      gene product overexpression (P = .0002 and P = .0006, respectively). Patients
      with 5c cell-positive tumors had a significantly worse 8-year survival rate (P =
      .003) than those with 5c cell-negative tumors. Subgroup analysis showed that the
      presence of 5c cells had a prognostic impact in low malignancy tumors, ie, in
      well-differentiated (grade I or II) and slowly proliferating tumors. Our findings
      suggest that determination of 5c cells may be a useful additional prognostic
      factor in axillary node-negative breast cancer. It adds prognostic information,
      especially in cases that are otherwise thought to have a favorable course.

PMID- 8276383
TI  - The presence of human papillomavirus in sinonasal papillomas, demonstrated by
      polymerase chain reaction with consensus primers.
AB  - The frequency of human papillomavirus (HPV) in sinonasal papillomas seems to vary
      considerably. The highest frequencies have been reported by investigators using
      in situ DNA or RNA hybridization. Few studies have used polymerase chain
      reaction, and in these reports the frequency of HPV detection is rather low. We
      have investigated the presence of HPV in sinonasal papillomas using the
      polymerase chain reaction with a set of degenerated consensus primers, which
      amplify the vast majority of the known HPV types. Human papillomavirus was found
      in three of 14 papillomas. By in situ hybridization the same three papillomas
      were positive for HPV type 6/11.

PMID- 8276384
TI  - Cell kinetic classification of tumors of the nervous system by DNA precursor
      labeling in vitro.
AB  - We studied 142 excisional or needle biopsy specimens of nervous system tumors
      with tritiated thymidine or 5'-bromodeoxyuridine (BrdUrd). Either precursor gave
      similar results. A labeling index (LI), expressed as a percentage and
      representing the S-phase fraction, was measured by a microscopic count from
      stained sections. The in vitro method ranked mean and median LIs of different
      neoplasms similarly to reported results from the in vivo administration of BrdUrd
      and reflected clinical aggressiveness of various tumor types. Gliosis,
      myxopapillary ependymomas, benign meningiomas, neurilemmomas, and pituitary
      adenomas consistently showed LIs less than 1%. The LI of a cerebellar Lhermitte
      Duclos gangliocytoma was zero, indicating the virtual absence of proliferation.
      Mean LIs and standard deviations of other tumors were as follows: anaplastic
      astrocytomas, 3.07% +/- 2.98%; glioblastoma multiforme, 6.15% +/- 5.61%; non
      Hodgkin's lymphoma, 12% +/- 9.5%; and metastatic neoplasms, 15% +/- 8.5%. The
      survival rate of patients with astrocytic tumors was inversely proportional to
      the LI. We conclude that the in vitro method is a practical alternative to in
      vivo BrdUrd administration for measurement of S-phase cells in tumors of the
      nervous system that gives prognostically useful information. Combination of
      BrdUrd LI with growth fraction measurement by monoclonal antibodies could offer
      new insights into brain tumor cell kinetics.

PMID- 8276385
TI  - The pattern and phenotype of T-cell infiltration associated with human liver
      allograft rejection.
AB  - Although transplant biopsy remains the best means for assessing liver allograft
      dysfunction, the presence and degree of rejection often is difficult to determine
      by current histologic criteria. The added diagnostic and prognostic value of
      examining liver allograft biopsy specimens by immunopathologic methods, such as
      phenotyping inflammatory cell infiltrates, has been inconclusive. To examine the
      value of assessing the phenotype and location of T-cell infiltrates we compared
      findings in 20 liver transplant biopsy specimens obtained from patients
      undergoing allograft rejection with those in 20 biopsy specimens from patients
      with no evidence of rejection. Serial frozen sections from all biopsies were
      labeled by immunoperoxidase techniques using monoclonal antibodies to identify
      cells expressing CD3, CD4, CD8, CD45RA, and CD45RO. As expected, the median of
      average cell infiltrates was higher in the rejecting versus nonrejecting group
      for each cell phenotype and region. However, statistical comparisons indicated
      that only some combinations of cell phenotype and location were significantly
      greater in the rejecting versus nonrejecting groups. The median number of portal
      CD3+ T cells per high-power field was increased in the rejecting versus
      nonrejecting groups (15.15 v 5.00 cells/high-power field; P < .01). This
      primarily was the result of a significant increase in CD8+ cells (7.15 v 1.55
      cells/high-power field; P < .0001). Examination of cells expressing CD45 isoforms
      also revealed a suggested increase (P < .04) in CD45RO+ "memory" but not in
      CD45RA "naive" T cells infiltrating portal areas. In lobular areas cell
      infiltrates of any examined phenotype were not significantly increased in the
      rejecting versus nonrejecting groups. These findings indicate that during liver
      allograft rejection the most characteristic changes involve an increase in T
      cells infiltrating the graft in portal regions and suggest that human liver
      allograft rejection preferentially involves memory CD8+ T cells directed at
      portal structures.

PMID- 8276386
TI  - Malignant schwannoma with melanocytic and neuroepithelial differentiation in an
      infant with congenital giant melanocytic nevus: a complex neurocristopathy.
AB  - We describe an infant girl, born with a pigmented giant nevus, who developed a
      malignant schwannoma in the retroperitoneum at 16 months of age. At birth the
      nevus covered over 50% of her body and histologically was a compound nevus with
      extension into the deep dermis surrounding dermal appendages. The malignant
      schwannoma was biphasic with areas composed of spindle and round cells.
      Ultrastructurally, the majority of the tumor cells exhibited a Schwann cell
      phenotype, but neuroepithelial and melanocytic cells were identified as well. We
      believe that this constellation of findings represents a form of
      neurocristopathy. Neurocristopathy, as defined by Bolande (Hum Pathol 5:409-429,
      1974), is a disease that results from aberrations in the migration, growth, or
      cytodifferentiation of neural crest tissues. These diseases may be simple (a
      singular pathologic process, usually localized) or complex (multiple
      neuroectodermal lesions). We report this case because the occurrence of
      retroperitoneal malignant schwannoma arising in a 16-month-old infant born with a
      pigmented giant nevus is unique, and may represent a previously undescribed form
      of a complex neurocristopathy.

PMID- 8276387
TI  - Improved predictive carrier testing for familial adenomatous polyposis using DNA
      from a single archival specimen and polymorphic markers with multiple alleles.
AB  - Familial adenomatous polyposis (FAP) is an autosomal dominant inherited condition
      caused by mutations in a candidate tumor suppressor gene, adenomatous polyposis
      coli. Predictive carrier testing for FAP can be accomplished by DNA linkage or
      mutation detection analysis. In many FAP families all affected individuals are
      deceased. Archival tissue specimens, if available from such patients, are a
      useful source of DNA for molecular analysis. We investigated the carrier risk of
      a presymptomatic 5-year-old girl with a family history of FAP. An archival
      specimen of normal colonic tissue was only available from the proband's affected
      deceased father. We screened DNA extracted from this specimen with dinucleotide
      repeat (CA/GT)n polymorphic marker (D5S346) linked to the adenomatous polyposis
      coli gene and established that the proband is at more than 99% risk of developing
      FAP. The proband's increased risk status was subsequently confirmed by
      identification of a germline adenomatous polyposis coli gene mutation consisting
      of a 5 base pair deletion at codon 1061. This strategy of using DNA from archival
      specimens of affected, unavailable FAP patients will increase the number of at
      risk individuals that can be diagnosed presymptomatically.

PMID- 8276388
TI  - Visceral leishmaniasis in the acquired immunodeficiency syndrome: report of two
      cases.
AB  - Core biopsies of the bone marrow are indispensable in the evaluation of fever of
      unknown etiology in human immunodeficiency virus-positive patients. We report two
      patients in whom visceral leishmaniasis was diagnosed based on the typical
      morphology, staining characteristics, and ultrastructure of the organisms.

PMID- 8276389
TI  - ADASP recommendations: consultations in surgical pathology. Association of
      Directors of Anatomic and Surgical Pathology.

PMID- 8276390
TI  - The program director and the chair--a relationship in need of definition.

PMID- 8276391
TI  - The health effects of agrichemicals: herbicides and soft tissue sarcomas.

PMID- 8276392
TI  - A yeast artificial chromosome contig linking the steroid sulfatase and Kallmann
      syndrome loci on the human X chromosome short arm.
AB  - In this report we describe the construction of a yeast artificial chromosome
      (YAC) contig linking the steroid sulfatase (STS) and Kallmann syndrome (KAL) loci
      on Xp22.3. Four human YAC libraries were screened initially with sequences from
      DXS237 (GMGX9), DXS278 (S232B), and KAL and later with primers from exon 10 of
      the STS gene and the end fragment of a YAC clone YGX3 to fill the gaps. Fifteen
      clones were isolated and the sizes of their human inserts were determined by
      pulsed-field gel electrophoresis followed by Southern hybridization with labeled
      total human DNA. Overlaps between the YAC clones were evaluated using more than
      20 DNA markers, including the screening probes, the end fragments, and the Alu
      PCR products of the YAC clones. The extent of overlapping between the clones was
      further determined by long-range restriction mapping. In combination with our
      previously reported YAC contigs around STS and KAL, a total of 2 Mb of Xp22.3
      have been isolated in YAC clones. These clones will facilitate the isolation of
      new genes and the characterization of deletions and translocations which occur at
      very high frequency in this region of the human X chromosome.

PMID- 8276393
TI  - cDNA cloning of the two subunits of human CAAX farnesyltransferase and
      chromosomal mapping of FNTA and FNTB loci and related sequences.
AB  - The CAAX farnesyltransferase is a heterodimeric enzyme that attaches a farnesyl
      group to a single cysteine in several cellular proteins. Substrates include the
      p21ras proteins, nuclear lamins, and several retinal proteins, all of which end
      with a "CAAXbox," where C is cysteine, A is an aliphatic amino acid, and X is
      methionine or serine. Full-length cDNAs for the alpha and beta subunits of the
      rat farnesyltransferase have been cloned, and both have been shown to be
      essential for catalytic activity. Here we have used the rat cDNAs to clone cDNAs
      for the human alpha and beta subunits. Comparison of the human and rat amino acid
      sequences revealed a remarkable degree of conservation (93% identity for the
      alpha subunit and 96% identity for the beta subunit). The functional genes for
      the alpha and beta subunits of human farnesyltransferase (gene symbols, FNTA and
      FNTB) were localized to human chromosome bands 8p22-q11 and 14q23-q24,
      respectively, by Southern blot hybridization and PCR analyses of panels of human
      x Chinese hamster somatic cell hybrid lines and by fluorescence chromosomal in
      situ hybridization. We also found several related farnesyltransferase genes.
      FNTAL1 was assigned to 11q13.4-q14.1, FNTAL2 to chromosome 13, and FNTBL1 to
      chromosome 9.

PMID- 8276394
TI  - Rapid evolution of horse satellite DNA.
AB  - The major satellite of the horse genome consists of about 1 million copies of a
      221-bp tandem repeat unit. By fluorescence in situ hybridization it has been
      localized in the centromeres of 58 of the 64 horse chromosomes. The donkey genome
      contains a similar but not identical satellite. Strikingly, the equine repeat did
      not hybridize to DNA of the Grevy zebra, despite the divergence of the horse and
      zebra only 3 to 5 million years ago and the ability of these species to
      crossbreed. The evolution of satellite DNA in the Equidae is more rapid than that
      in other mammalian families, which may be explained by their rapid karyotypic
      evolution.

PMID- 8276395
TI  - The exon-intron organization of the human erythroid beta-spectrin gene.
AB  - The human erythrocyte beta-spectrin gene DNA has been cloned from overlapping
      human genomic phage and cosmid recombinants. The entire erythroid beta-spectrin
      mRNA is encoded by 32 exons that range in size from 49 to 871 bases. The
      exon/intron junctions have been identified and the exons mapped. There is no
      correlation between intron positions and the repeat units of 106 amino acids
      within domain II of the beta-spectrin gene. The scatter of the introns over the
      17 repeats argues against the 106-amino-acid unit representing a minigene that
      underwent repeated duplication resulting in the present beta-spectrin gene. In
      fact, the two largest exons, exon 14 (871 bp) and 16 (757 bp), extend over 4 and
      3 repeat units of 106 amino acids, respectively, while repeat beta 10 is encoded
      by 4 exons. No single position of an intron in the beta-spectrin gene is
      conserved between any of the 17 beta-spectrin and 22 alpha-spectrin repeat units.
      The nucleotide sequences of the exon/intron boundaries conform to the consensus
      splice site sequences except for exon 20, whose 5' donor splice-site sequence
      begins with GC. The beta-spectrin isoform present in the human brain, the
      skeletal muscle, and the cardiac muscle is an alternatively spliced product of
      the erythroid beta-spectrin gene. This splice site is located within the coding
      sequences of exon 32 and its utilization in nonerythroid tissues leads to the use
      of 4 additional downstream exons with a size range of 44 to 530 bp.

PMID- 8276396
TI  - Chromosomal organization of mammalian POU domain factors.
AB  - We present the chromosomal locations in mouse of eight new members of the
      mammalian POU domain family of transcriptional regulators. Chromosomal
      assignments were made for Brn-1 (Chr 1), Brn-2 (Chr 4), Brn-4 (Chr X), Brn-3.0
      (Chr 14), Brn-3.1 (Chr 18), Brn-5.0 (Chr 15), Skn-1a/i (Chr 9), and Sprm-1 (Chr
      13) in addition to the previously reported Pit-1 (Chr 16), Tst-1 (Chr 4), Oct-3/4
      (Chr 17), Oct-1 (Chr 1), and Oct-2 (Chr 7) genes. Several conclusions have
      emerged from this analysis. First, among the most highly related family members
      (Brn-1, Brn-2, Brn-4, and Tst-1; Brn-3.0 and Brn-3.1; Oct-1, Oct-2, and Skn-1a/i)
      no chromosomal linkage is noted. Second, no clusters of genes are observed,
      irrespective of homology. Finally, no obvious linkages to genes for known
      additional regulatory factors with a specific origin of cell type are apparent.
      Thus, members of this large gene family, presumably arising as duplication events
      from common ancestral genes, apparently function in distinct chromosomal milieu
      under independent regulation. Some of these newly localized genes map in close
      proximity to existing mouse mutations.

PMID- 8276397
TI  - Murine chromosomal location of four class III POU transcription factors.
AB  - A family of mouse genes encoding class III POU transcription factors consists of
      four members: Oct-6, Brn-2, Brn-1, and Brn-4. In accordance with mouse
      nomenclature, these loci have been designated Otf-6, Otf-7, Otf-8, and Otf-9,
      respectively. While the four genes share a highly conserved class III POU domain,
      the remaining regions are considerably diverged from each other. The POU domains
      of these transcription factors recognize the octamer-motif sequence and possess a
      similar DNA-binding specificity. Chromosomal mapping has demonstrated that the
      four genes are unlinked: Otf-6 is located on the distal region of chromosome 4,
      Otf-7 on the proximal region of chromosome 4, Otf-8 on chromosome 1, and Otf-9 on
      the X chromosome.

PMID- 8276398
TI  - The gene for creatine kinase, mitochondrial 2 (sarcomeric; CKMT2), maps to
      chromosome 5q13.3.
AB  - YAC clones for the creatine kinase, mitochondrial 2 (sarcomeric; CKMT2), gene
      were isolated. One of these YACs was localized on chromosome 5q13.3 by
      fluorescence in situ hybridization. A polymorphic dinucleotide repeat
      (heterozygosity 0.77) was identified within the seventh intron of the CKMT2 gene.
      Genotyping of CEPH families allowed positioning of CKMT2 on the multipoint map of
      chromosome 5 between D5S424 and D5S428, distal to spinal muscular atrophy (SMA)
      (5q12-q14).

PMID- 8276399
TI  - Cloning and characterization of the mouse short-chain acyl-CoA dehydrogenase
      cDNA.
AB  - Short-chain acyl-CoA dehydrogenase (SCAD) is one of five homologous
      dehydrogenases that catalyze the first reaction in the beta-oxidation of fatty
      acids. As the name implies, the substrate for this enzyme is short-chain acyl-CoA
      (C4-C6). We report here the coding and 3'UT sequence of the cDNA for mouse
      precursor SCAD. The mouse SCAD cDNA coding sequence covers 1239 bp. This
      represents a 24-amino-acid leader peptide and a 388-amino-acid mature peptide.
      Comparison of this sequence with reported rat and human SCAD cDNA sequences
      reveals a high degree of homology among the three species. Comparison of the
      amino acid sequence with that of other acyl-CoA dehydrogenases, medium-chain acyl
      CoA dehydrogenase and long-chain acyl-CoA dehydrogenase, also shows a high degree
      of homology.

PMID- 8276400
TI  - Mammalian homologues of the Drosophila Son of sevenless gene map to murine
      chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively.
AB  - Activating mutations in the ras genes are commonly found in a wide range of human
      tumors. We recently cloned two mammalian genes, Son of sevenless 1 (mSos1) and
      Son of sevenless 2 (mSos2), whose protein products appear to be important
      positive regulators of ras proteins. Given the proposed role of Sos proteins in
      ras regulation, and the frequent occurrence of activated ras alleles in tumor
      cells, we were interested in determining whether the Sos genes may also be
      activated inappropriately by DNA rearrangement in tumor cells. To investigate
      this possibility, we have determined the chromosomal locations of both the mouse
      and the human Sos1 and Sos2 genes, using a combination of genetic linkage
      analysis and in situ hybridization to chromosomal spreads. We find that the
      murine Sos1 and Sos2 genes map to chromosomes 17E and 12C3.3-D and their human
      counterparts to chromosomes 2p21-2p2 and 14q21, respectively. Neither the human
      nor the mouse Sos loci map close to known mutations or to regions showing
      consistent karyotypic abnormalities in tumor cells.

PMID- 8276401
TI  - Assignment of four sequence-tagged sites to three subregions of 13q12 using a
      somatic cell hybrid mapping panel.
AB  - To define the position of a 13q12 breakpoint from a patient with
      ganglioneuroblastoma, a series of somatic cell hybrids carrying human chromosome
      translocations with breakpoints in the proximal part of chromosome 13 has been
      compiled. Sequence-tagged sites (STS) have been generated from a series of Alu
      PCR probes previously shown to be in the 13q12 region. Together with an STS for
      the oncogene FLT1, these have been used to define the relative positions of the
      translocation breakpoints in the hybrids. In this way, four markers have been
      ordered in three subregions of 13q12 and reference breakpoints established. The
      refined physical map of 13q12 provides a series of reference markers with known
      locations and will be invaluable in the further characterization of breakpoints
      in this region.

PMID- 8276402
TI  - Chromosome mapping of human CDC25A and CDC25B phosphatases.
AB  - The human CDC25 tyrosine phosphatases trigger activation of CDC2 by removing
      inhibitory phosphates; thus the genes encoding these phosphatases may be
      suspected as potential oncogenes due to their role in promoting cell division. To
      date, three human CDC25 genes have been identified: CDC25A, B, and C. This
      communication describes the mapping of CDC25A to chromosome 3p21 and CDC25B to
      chromosome 20p13 by fluorescence in situ hybridization with confirmation by the
      polymerase chain reaction of hamster-human somatic cell hybrid DNA. 3p21 is near
      an area frequently involved in karyotypic abnormalities in renal carcinomas,
      small cell carcinomas of the lung, and benign tumors of the salivary gland. 20p13
      does not seem to be a common area for karyotypic alteration in tumors. Mapping of
      these genes to their chromosomal loci may help identify tumors with abnormal
      regulation of CDC25 genes due to genomic alterations.

PMID- 8276403
TI  - The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster
      of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13.
AB  - The leukemia inhibitory factor receptor (LIFR) gene was localized to human
      chromosome 5p12-p13 by somatic cell hybrid analysis. Interspecific backcross
      analysis revealed that the murine locus was on chromosome 15 in a region of
      homology with human chromosome 5p. In both human and mouse genomes, the LIFR
      locus was linked to the genes encoding the receptors for interleukin-7,
      prolactin, and growth hormone.

PMID- 8276404
TI  - Isolation and characterization of 14 CA-repeat microsatellites from human
      chromosome 21.
AB  - Fourteen CA-repeat microsatellite polymorphisms from human chromosome 21 (HC21)
      (D21S364, D21S365, D21S366, D21S367, D21S368, D21S369, D21S406, D21S407, D21S408,
      D21S409, D21S410, D21S411, D21S415, and D21S1217) have been cloned from a flow
      sorted phage library (LA21NS01). These microsatellite loci have been mapped using
      a somatic cell hybrid panel of HC21, and heterozygosities and allele frequencies
      have been determined. The markers spread along the length of the long arm of the
      HC21. Twelve of these microsatellites have heterozygosities between 0.47 and
      0.90. These new CA-repeat markers will improve the genetic map of HC21.

PMID- 8276405
TI  - Smooth muscle myosin heavy chain locus (MYH11) maps to 16p13.13-p13.12 and
      establishes a new region of conserved synteny between human 16p and mouse 16.
AB  - The human smooth muscle myosin heavy chain locus (MYH11) was mapped by
      fluorescence in situ hybridization to the middle of the p arm of chromosome 16
      using a genomic cosmid clone containing coding sequences of the gene as probe.
      Probe from coding sequence, when applied to Southern blots of a panel of hybrids
      containing different portions of human chromosome 16, localized the gene to
      16p13.13-13.12. Coding sequence PCR primers, when used on the DNA from a CHO
      mouse hybrid clone mapping panel informative for mouse chromosomes, showed that
      the gene was located on mouse chromosome 16. These results correct a recent
      assignment of MYH11 from 16q12.2 to the region of the 16p-arm inversion
      breakpoint seen in acute myelomonocytic leukemia (AMML) M4Eo and demonstrate that
      the conflicting data do not result from the presence of additional MYH genes on
      the q arm of the chromosome. Also, a new region of conserved synteny between
      human 16p and mouse 16 is established.

PMID- 8276406
TI  - Assignment of the human tear lipocalin gene (LCN1) to 9q34 by in situ
      hybridization.

PMID- 8276407
TI  - The D4 dopamine receptor gene maps on 11p proximal to HRAS.

PMID- 8276408
TI  - Localization of a novel ryanodine receptor gene (RYR3) to human chromosome 15q14
      q15 by in situ hybridization.

PMID- 8276409
TI  - Reverse mapping of the gene encoding the human fos-related antigen-1 (fra-1)
      within chromosome band 11q13.

PMID- 8276410
TI  - Localization of the genes encoding the melanocortin-2 (adrenocorticotropic
      hormone) and melanocortin-3 receptors to chromosomes 18p11.2 and 20q13.2-q13.3 by
      fluorescence in situ hybridization.

PMID- 8276411
TI  - The gene for human erythrocyte membrane protein band 7.2 (EPB72) maps to 9q33-q34
      centromeric to the Philadelphia chromosome translocation breakpoint region.

PMID- 8276412
TI  - Sublocalization of 21 chromosome 18-specific microsatellite markers.

PMID- 8276413
TI  - Identification of an A-to-G missense mutation in exon 2 of the UGT1 gene complex
      that causes Crigler-Najjar syndrome type 2.

PMID- 8276414
TI  - The gamma-globin genes and their flanking sequences in primates: findings with
      nucleotide sequences of capuchin monkey and tarsier.
AB  - By sequencing extensive regions of the beta-globin gene cluster from capuchin
      monkey (New World monkey) and tarsier (prosimian) we confirmed that capuchin
      monkey and tarsier have two and one gamma-globin gene(s), respectively. These
      findings indicate that the ancestral anthropoid gamma-globin gene duplicated
      after anthropoids diverged from tarsier, but before they diverged into
      platyrrhines (New World monkeys) and catarrhines (Old World monkeys, apes, and
      human). The capuchin monkey gamma 1-globin gene promoter region accumulated many
      nucleotide substitutions, including a T to C substitution in the proximal CCAAT
      element. This adverse mutation, along with the previous finding that the gamma 1
      locus in spider monkey is a pseudogene, suggests that in platyrrhines the gamma 2
      globin gene may be the primary fetal beta-like globin gene. The aligned gamma
      gene sequences contain several conserved sequence elements (phylogenetic
      footprint) of 6 bp or longer in the 5' flanking region, but none in the 3'
      flanking region. Gene conversions frequently occurred in the 5' flanking and
      transcribed regions of the duplicated genes of anthropoids but rarely in the 3'
      flanking sequences. However, an absence of conversions within the capuchin and
      spider monkeys promoter regions suggests that in platyrrhines selection acted
      against conversions as they could decrease (or inactivate) gamma 2 expression.

PMID- 8276415
TI  - Fixation times of retroposons in the ribosomal DNA spacer of human and other
      primates.
AB  - We have investigated the presence/absence of two types of retroposed sequences
      found in human ribosomal DNA in equivalent positions in chimpanzee, gorilla,
      orangutan, gibbon, and rhesus monkey rDNA. These sequences are one pseudogene
      derived from the single-copy cdc27hs gene and seven complete Alu elements. The 2
      kb pseudogene is present in the apes but not in Old World monkeys, indicating
      fixation in an ape ancestor. Five of the Alu elements are shared by the whole set
      of primates studied, indicating insertion and fixation prior to the split of the
      ape and Old World monkey lineages. One is absent only from the rhesus monkey
      rDNA, and another is absent from both gibbon and rhesus rDNA, indicating fixation
      at different times in primate evolutionary history. Since branching times for the
      primate phylogenetic tree are known from a combination of the fossil record and
      multiple molecular data sets, it is possible to compare Alu fixation times
      determined from the phylogenetic information with those calculated from Alu
      element mutation rates.

PMID- 8276416
TI  - The mouse apolipoprotein C1 gene: structure and expression.
AB  - We have isolated and characterized cDNA and genomic clones containing the mouse
      apolipoprotein C1 (Apoc1) gene. The Apoc1 gene is part of the Apoe-c1-c2 gene
      cluster and is located 3.4 kb 3' of the Apoe gene. The mouse Apoc1 gene spans a
      region of approximately 3.3 kb and consists of four exons. The exon-intron
      structure is similar to those of human and baboon genes, although in mouse
      introns 2 and 3 are smaller. Significant sequence homology is found between man
      and mouse in the promoter and exonic regions (80 and 67%, respectively). Northern
      blotting and primer extension analysis of mouse RNA showed that a major
      transcript 409 bp in size is expressed primarily in fetal and adult liver. The
      mouse Apoc1 cDNA contains an open reading frame encoding a protein of 88 amino
      acids, including a signal peptide of 26 amino acid residues. Comparisons of the
      deduced amino acid sequence of mouse apoC1 with the human, baboon, rat, and dog
      sequences showed discrete regions with a high degree of conservation. The
      delineation of the sequence and structural organization of the mouse Apoc1 gene
      is an essential step in enhancing the use of mouse models to study the function
      of apoC1 in the lipoprotein metabolism.

PMID- 8276417
TI  - Genetic and physical mapping of the Treacher Collins syndrome locus with respect
      to loci in the chromosome 5q3 region.
AB  - Treacher Collins syndrome is an autosomal dominant, craniofacial developmental
      disorder, and its locus (TCOF1) has been mapped to chromosome 5q3. To refine the
      location of the gene within this region, linkage analysis was performed among the
      TCOF1 locus and 12 loci (IL9, FGFA, GRL, D5S207, D5S210, D5S376, CSF1R, SPARC,
      D5S119, D5S209, D5S527, FGFR4) in 13 Treacher Collins syndrome families. The
      highest maximum lod score was obtained between loci TCOF1 and D5S210 (Z = 10.52;
      theta = 0.02 +/- 0.07). The best order, IL9-GRL-D5S207/D5S210-CSF1R-SPARC-++
      +D5S119, and genetic distances among these loci were determined in the 40 CEPH
      families by multipoint linkage analysis. YAC clones were used to establish the
      order of loci, centromere-5'GRL3'-D5S207-D5S210-D5S376-CSF1R -SPARC-D5S119
      telomere. By combining known physical mapping data with ours, the order of
      chromosome 5q3 markers is centromere-IL9-FGFA-5'GRL3'-D5S207-D5S210- D5S376-CSF1R
      SPARC-D5S119-D5S209- FGFR4-telomere. Based on this order, haplotype analysis
      suggests that the TCOF1 locus resides distal of CSF1R and proximal to SPARC
      within a region less than 1 Mb in size.

PMID- 8276418
TI  - High-resolution fluorescence mapping of 46 DNA markers to the short arm of human
      chromosome 1.
AB  - We describe a high-resolution cytogenetic map for 46 DNA markers previously
      assigned to the short arm of human chromosome 1. Using fluorescence in situ
      hybridization on simultaneously R-banded prometaphase chromosomes, a refined map
      position was found for 45 probes. For 6 of these probes, additional hybridization
      sites were observed and for another 7 probes, conflicting results were found with
      regard to previous localizations. For some probes with overlapping map positions,
      probe order could be determined by dual-color hybridization on elongated
      chromosomes. The present high-resolution map can be used to refine the previously
      published composite map and also provides additional landmarks for the
      construction of a contig map of the short arm of chromosomes 1.

PMID- 8276419
TI  - Structure and polymorphisms of the human annexin III (ANX3) gene.
AB  - A 75-kb region encompassing the human annexin III (ANX3) gene on chromosome 4q21
      was characterized from directly amplified genomic DNA and from six genomic clones
      in phage lambda (lambda ANX3-1 to lambda ANX3-6). The gene was mapped with
      restriction enzymes BamHI, EcoRI, HindIII, SacI, and XbaI, and primers were
      developed for nine sequence-tagged sites throughout the gene. The transcribed
      region spans 58 kb and contains 12 introns ranging from 0.3 to 19.1 kb and 13
      exons ranging from 53 to 374 bases. Northern blots showed a single mRNA species
      of approximately 1.7 kb in all tissues examined. Three intragenic polymorphisms
      were identified: a tandem repeat of the sequence TAAA with at least six alleles,
      a two-allele SalI polymorphism detectable by polymerase chain reaction, and a two
      allele BglII polymorphism.

PMID- 8276420
TI  - Chromosomal mapping of the human Mu class glutathione S-transferases to 1p13.
AB  - The chromosomal localization of the human Mu class glutathione S-transferase
      (GST) genes has been complicated by two factors; the total number of genes is
      unknown and there is a polymorphism that results from the presence or absence of
      the GSTM1 gene. Three human Mu class glutathione S-transferase isoenzymes, GSTM1,
      GSTM2, and GSTM3, have been characterized previously, and we have recently cloned
      and characterized GSTM4, another member of this class. Here we report that a
      probe derived from GSTM4 cross-hybridizes with the other three known human Mu
      class GST genes. In situ hybridization with the GSTM4 probe localized a major
      region of hybridization on chromosome band 1p13. Although there is a region of
      very weak hybridization on chromosome 6, these data indicate that the human Mu
      class gene family is largely clustered and not dispersed on different
      chromosomes. The identical hybridization patterns in individuals with or without
      the GSTM1 gene suggest that this locus is a component of the Mu class GST gene
      cluster.

PMID- 8276421
TI  - Physical mapping of a functional cluster of epidermal differentiation genes on
      chromosome 1q21.
AB  - Genes of three protein families, which are in part specifically expressed in the
      course of terminal differentiation of human epidermis, have previously been
      mapped to chromosome 1q21. Here we show that these genes are physically linked
      within 2.05 Mb of DNA. The order is calpactin I light chain, trichohyalin,
      profilaggrin, involucrin/small proline-rich protein, loricrin, and calcyclin. The
      colocalization in the 1q21 region together with their functional interdependence
      during epidermal differentiation raises the question whether these genes share
      regulatory elements which control their transcriptional activities. As several of
      them are potential candidate genes for dyskeratotic skin diseases, this physical
      map should be of great value for genetic linkage analyses.

PMID- 8276422
TI  - Sensitivity of non-cooperative binding parameters of ligand-DNA complex by
      computer analysis.
AB  - A simple user-friendly computer programme has been developed to operate on an IBM
      PC compatible machine to aid in the process of curve fitting using the McGhee and
      von Hippel equation [J. Mol Biol, 86 (1974), 469-489] for the analysis of ligand
      DNA interactions and the experimental data on berberine-calf thymus DNA and
      berberine-poly(dI-dC). poly(dI-dC) for non-cooperative binding. A sensitivity
      analysis on binding constant (K0) and the number of binding sites (N0) show that
      a small variation in the latter remarkably alters the fitting curve. At a level
      of 1% change in N0 from the best fit value, the standard deviation grows by
      almost 4%, while, on the other hand, a 1% change in K0 affects the same value
      only by less than 0.4%.

PMID- 8276423
TI  - Proton liberation in the pre-steady state phase of creatine kinase.
AB  - Numerous stereochemical and kinetic investigations on the reaction pathway of
      creatine kinase (CK) suggest that this enzymic reaction proceeds via direct in
      line transfer of phosphate between participating substrates and to date there has
      been no chemical evidence for any plausible intermediate between enzyme-substrate
      and enzyme-product complexes. By following the absorption pattern of a pH
      sensitive dye (o-cresol sulphonaphthalein) in a stopped flow module we have
      studied transient pH changes in the backward reaction of CK. While the rapid
      mixing of ADP and CK gives no pH transient, that of phosphocreatine (PCr) and CK
      gives H+ liberation with kapp of 62.8 sec-1. The magnitude of proton release is
      one H+ per monomer of CK. Mixing of PCr+CK with ADP does not give any detectable
      pH transient and the reaction immediately proceeds to steady phase. The mixing of
      ADP+CK with PCr again gives a release of 1.2 H+ per monomer of CK with kapp of
      around 67.2 sec-1 before the reaction proceeds to steady phase where there is
      absorption of one H+ per ADP transphosphorylated. The results obtained,
      therefore, indicate the involvement of proton deficient E.PCr and E.ADP.PCr
      complexes in the pathway of CK.

PMID- 8276424
TI  - Evidence for beta-galactosidase catalyzed hydrolysis of paranitrophenyl-beta-D
      galactopyranoside anchored in cyclodextrins.
AB  - The absorption maximum of p-nitrophenol upon mixing with molar equivalents of
      alpha-cyclodextrin (alpha-CD) or hydroxypropyl-beta-cyclodextrin (HPB) showed
      nearly 5 nm shift to the longer wavelength region, indicative of complex
      formation, while beta-cyclodextrin (beta-CD), gamma-cyclodextrin (gamma-CD) and
      hydroxyethyl-beta-cyclodextrin (HEB) produced only a marginal shift of about 1-2
      nm, suggestive of a weaker interaction. It has been shown by circular dichroism
      spectral studies that the aglycon part of p-nitrophenyl-beta-D-glycoside (PNPG)
      is also encapsulated by alpha-cyclodextrin. The encapsulated form of PNPG could
      be hydrolyzed by beta-galactosidase, the temperature and pH-optima for hydrolysis
      of anchored substrates being essentially identical to that of free substrate.
      However, small but consistent increase in Km values were obtained for alpha
      cyclodextrin-, HEB- and HPB-anchored substrates. The kcat values also registered
      an increase for the HEB- and HPB-anchored substrates. However, there was no
      increase in kinetic efficiency (kcat/Km) of enzyme. The inhibition noted at
      higher concentrations of HEB- and gamma-cyclodextrin-anchored PNPG but not with o
      nitrophenyl-beta-D-galactoside (ONPG)-cyclodextrin mixture suggests that PNPG
      cyclodextrin complexes were responsible for the inhibition. Taken together, these
      results suggest that the enzyme catalyses the hydrolysis of anchored substrates.

PMID- 8276425
TI  - Studies on iron binding by free fatty acids.
AB  - The effect of various saturated and unsaturated fatty acids on iron binding and
      the translocation of this complex into the organic phase were studied. The amount
      of iron translocated into the organic phase depended on the affinity of the
      respective fatty acid to iron. It was seen that saturated and monounsaturated
      fatty acids translocated more iron compared to polyunsaturated fatty acids.
      Positional isomers of oleic acid were as effective as oleic acid in translocating
      iron. It appears that the free carboxyl group on the fatty acid is essential, as
      the methyl ester of the fatty acid failed to translocate iron. Effect of varying
      the concentration of fatty acid and iron on iron translocation suggested the
      requirement of 3 to 4 moles of fatty acid for 1 mole of iron binding. Divalent
      cations such as Ca2+ and Mg2+ or lipids such as cholesterol or triolein did not
      compete with fatty acids but there was reduced translocation when phosphate
      buffer or phospholipid was included in the incubation medium, suggesting that
      phosphate interferes with the formation of fatty acid-iron complex. Thus it seems
      that free fatty acids are capable of forming a complex with iron.

PMID- 8276426
TI  - Metabolism of 5-aminoquinoline with liver cytosol enzyme.
AB  - In vitro oxidation and acetylation of 5-aminoquinoline by rabbit liver enzyme
      preparation has been investigated. Incubation of 5-aminoquinoline with cytosol
      fraction of the enzyme preparation in the presence of acetyl coenzyme-A gave rise
      to three different products, viz. 5-amino-2-hydroxy quinoline, 5-acetyl
      aminoquinoline and 5-acetylamino-2-hydroxy quinoline due to the combined action
      of aldehyde oxidase and N-acetyl transferase. The metabolites thus obtained by
      enzyme catalysed reactions were isolated and separated by TLC, HPLC and
      subsequently characterised by IR and mass spectral fragmentation techniques.

PMID- 8276427
TI  - Structure-activity relationship studies of 4-substituted-2-guanidinothiazoles:
      reversible inhibitors of gastric (H+/K+)-ATPase.
AB  - The role of physicochemical factors, electronic and hydrophobic, and a hydrogen
      donor index in the inhibition of gastric (H+/K+)-ATPase by 4-phenyl-2
      guanidinothiazoles and the 4-indolyl-2-guanidinothiazoles has been quantitatively
      analysed. For the first congeneric series, the resonance effect of the ortho- and
      para-substituents and hydrogen donor property of the meta-substituent in the
      phenyl ring play crucial role, whereas for 4-indolyl analogues, the
      hydrophobicity and electron withdrawing effect of X-substituents in the indolyl
      ring are shown to be important decisive factors. Also the substitution of the
      guanidine moiety, e.g. by benzyl, raises the activity of proton pump inhibitors.
      The substitution at 5-position of thiazole ring does not enhance the potency.

PMID- 8276428
TI  - Plausible involvement of a diabetic serum factor in neutrophil membrane
      pathology.
AB  - With a view to determining the role of diabetic serum factor (DSF) in the
      progression of membrane pathology, time-dependent preincubation effects of DSF on
      certain membrane-bound enzymes of normal polymorphonuclear leucocytes (PMNL) have
      been studied. DSF is found to cause significant decrements in the activities of
      Na+/K+ ATPase, PLC and AcE of PMNL on in vitro incubation for 60 min, while the
      effect on Ca2+/Mg2+ ATPase appears only on prolonged incubation with an initial
      hike in activity at 5 min. The implications of these results have been discussed.

PMID- 8276429
TI  - Alterations in large gut associated lymphatic tissues (LGALT) during experimental
      colorectal carcinogenesis.
AB  - Alterations in large gut associated lymphatic tissues (LGALT) were studied
      histologically during 20-methylcholanthrene (MCA) induced colorectal
      carcinogenesis. Precancerous changes in LGALT included hyperplasia,
      hyperchromasia of lymphocytes and enlargement of lymphoid follicles. In addition,
      follicular invasion in muscular layer and cellular disorganization of diffuse
      lymphatic tissues were observed in neoplasia. Since, LGALT showed remarkable
      changes during carcinogenesis, this aspect may be considered during assessment of
      preneoplastic lesions, along with other histologic features of early neoplasia.

PMID- 8276430
TI  - Need of dietary energy at critical implantation time when local ovarian hormones
      are obligatory for conceptus development.
AB  - Role of dietary energy and local ovarian hormones in conceptus development in the
      rat was evaluated by giving ip injections of estrogen and progesterone under diet
      restricted and/or dextrose supplemented conditions, using the experimental model
      of ovarian compensatory hypertrophy. Replacement of estrogen on day 2 and
      progesterone on day 3 was necessary for conceptus development in the ipsilateral
      uterine horn after unilateral ovariectomy on day 2. Continuation of progesterone
      injection up to day 9 improved the percentage of conceptus development. Conceptus
      development was normal when unilateral ovariectomy was performed after day 2 of
      pregnancy. Compensatory increases in corpus luteum (CL) volume and the activity
      of delta 5 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD) in contralateral
      ovary were observed after unilateral ovariectomy on day 2-4 of pregnancy.
      However, 70% diet restriction reducing the energy intake (from 90 to 27
      kcal/rat/day) abolished the single dose hormone therapy effects in ipsilateral
      horn conceptus development and also reduced the effects of continued
      progesterone, percentage of contralateral horn conceptus development,
      compensatory changes in the CL volume and delta 5 3 beta-HSD activity of the
      contralateral ovary. However, dietary dextrose supplementation (increasing
      calorie intake from 27 to 56 kcal/rat/day) significantly improved/restored
      hormone response for conceptus development, compensatory changes of the CL volume
      and enzyme activity in contralateral ovary. The results suggest that day 2-3 of
      pregnancy is the critical time when local ovarian supply of estrogen and
      progesterone are obligatory for establishment and conceptus development in the
      rat. During this period adequate mobilizable source of energy is necessary for
      execution of hormonal message.

PMID- 8276431
TI  - Multiple neural inductions in area opaca by grafts of the Hensen's node do not
      retard host chick embryo development.
AB  - Four hundred and forty four full primitive streak stage chick embryos were
      cultured in vitro and 261 were transplanted with 1, 3 or 5 Hensen's nodes in the
      area opaca. Irrespective of the number of grafts, neural induction was observed
      in 90% cases. The development of control and grafted embryos and the size of
      blastoderm area were monitored at the time of grafting and after 20 hr. We find
      that the induced neural tissue and differentiated tissue of graft-origin neither
      fuse with the host embryonic axis, nor retard its development.

PMID- 8276432
TI  - Effects of nitrofurantoin on viability, DNA synthesis and morphology of Vibrio
      cholerae cells.
AB  - Nitrofurantoin caused a dose dependent inhibition of growth and decrease in
      viability of V. cholerae cells, the 10% (D10) and 37% (D37) survival doses being
      50 and 19 micrograms/ml respectively. The drug at a concentration of 60
      micrograms/ml caused 86% inhibition of DNA synthesis. Both light and electron
      microscopic observations revealed that treatment with nitrofurantoin (60
      micrograms/ml for 1 hr at 37 degrees C) led to a significant filamentation of the
      V. cholerae cells, ultrastructure of the cell cytoplasm, plasma membrane and cell
      wall however remaining unaltered from those of untreated cells. The results are
      discussed in relation to DNA lesions produced by and the carcinogenic potential
      of the drug.

PMID- 8276433
TI  - Evaluation of vanillic acid analogues as a new class of antifilarial agents.
AB  - A number of vanillic acid analogues (1-14) have been synthesised and evaluated
      against experimental filarial infections using cotton rats (Sigmodon hispidus)
      infected with Litomosoides carinii, a primary screening model, at a dose of 30
      mg/kg, ip for 5 days. Of the 8 compounds tested, 4 (5,7, 11 and 12) exhibited
      high micro- and macro-filaricidal activity with sterilization of surviving female
      worms. Compounds 5, 7, 12 showed remarkable adulticidal action (> 80%).
      Sterilization of the female worms by compounds 11 and 12 was highly significant
      (80-100%).

PMID- 8276434
TI  - Effect of piracetam on electroshock induced amnesia and decrease in brain
      acetylcholine in rats.
AB  - Piracetam, a prototype of a new class of psychotropic agents, the nootropic
      agents, which improve learning ability and memory retention, was found to induce
      a dose-related prevention of disruption of acquisition of a passive avoidance
      response produced by electroshock application. The amnesia attenuating effect of
      piracetam was accompanied by prevention of the decrease in acetylcholine
      concentrations of rat brain induced by electroshock. The study indicates that the
      cognition enhancing effect of piracetam may be due to a facilitatory effect on
      cholinergic transmission.

PMID- 8276435
TI  - Collagen levels in isoproterenol induced myocardial infarction in rats.
AB  - Myocardial infarction was induced in albino rats by the subcutaneous
      administration of isoproterenol. A significant was observed increase in weight of
      the myocardium, total protein, DNA levels, neutral salt soluble collagen content,
      serum and urinary hydroxyproline levels at peak infarction stage in treated rats
      while the body weight, insoluble and total collagen content of heart were found
      to be decreased. These results show an early degradation of collagen immediately
      after myocardial infarction and enhanced synthesis during the different stages of
      recovery. Histological studies confirmed the incidence of peak infarction after
      two doses of isoproterenol treatment and recovery to normalcy from the third day
      onwards.

PMID- 8276436
TI  - Effects of ECT-dothiepin combination on learning in rats.
AB  - Electroconvulsive therapy (ECT) and antidepressant drugs are each known to impair
      learning and memory. No information is available on their effects on cognition
      when used concurrently in the treatment of depression, as is frequent in India.
      In the present study, therefore, the effects of electro-convulsive shocks (ECS)
      and dothiepin, separately and in combination, were studied in an animal model
      employing a complex maze operant learning paradigm. ECS were given on alternate
      days (3/week) for 2 weeks. Dothiepin (10 mg/kg, ip) was administered once daily
      for 2 weeks. Learning was assessed on days 2-10 post-treatment ECS produced
      greater initial impairment in learning while dothiepin produced a more sustained
      impairment. While impairment was maximum in the combined treatment group, the
      statistical significances that emerged to proscribed the combination were but
      weak.

PMID- 8276437
TI  - Blood and hepatic glutathione in linamarin fed rats.
AB  - Female Sprague Dawley rats were fed 5 mg linamarin daily for 10 days. Reduced
      glutathione (GSH) levels in blood and liver of experimental rats were analysed.
      The results showed an increase of 45% and 33% glutathione levels in blood and
      liver respectively in experimental rats. This alteration in glutathione levels
      could be most likely either due to increased hepatic biosynthesis or as a
      consequence of decreased peripheral utilization which might be appreciated due to
      hypothyroidal status induced by linamarin feeding.

PMID- 8276438
TI  - Use of hydroxylamine in improving radio protection of a combination of 5-hydroxy
      L-tryptophan and a thiol compound (AET) in small mammals.
AB  - Radioprotective effectiveness has been evaluated by 30 day survival studies and
      protection to bone-marrow cells in mice after radiation exposure and this has
      been further established by 24 hr deoxycytidine excretion in urine of rats
      following 5 Gy whole body gamma irradiation and protection to superoxide
      dismutase enzyme in marrow cells and red blood corpuscles. Radioprotective
      effectiveness as well as the duration of radioprotection have been improved by
      the administration (ip) of hydroxylamine (20 mg/kg), a decarboxylase inhibitor,
      prior to the use of a combination of 5-hydroxy L-tryptophan (5-HTP, 70 mg/kg) and
      2-aminoethylisothiuronium bromide hydrobromide (AET, 20 mg/kg) ip in small
      mammals before whole body gamma irradiation.

PMID- 8276439
TI  - Effect of some chemical radioprotectors on mouse bone marrow.
AB  - Effect of HT, AET and Se on mice bone marrow has been studied by counting bone
      marrow micronucleated cells and endogenous spleen colony count (CFU-S).
      Combination of HT and AET used as a radioprotector has not caused any significant
      variation in any of the parameter studied when administered once, it increases
      bone marrow micronucleated cells and decreases CFU-S slightly after daily
      administration for 7 days. The individual constituent of the combination
      administered singly does not increase micronucleated cell number. Seven
      consecutive doses of HT + AET and same in combination with Se enhances
      micronucleated cells to a higher level. Daily injection of Se alone up to 7 days
      also causes an increase in micronucleated cells upto same level. CFU-S pool does
      not show any significant change in number of bone marrow cells through out the
      study except in the groups where animals were treated with Se.

PMID- 8276440
TI  - Radioprotection of chick thymus by vitamin E.
AB  - One day and 7 days old male white leghorn chicks were administered vitamin E
      prior to their exposure to sublethal dose (2.25 Gy) of gamma radiation from 60C
      source. The results show that vitamin E helps in faster recovery of damage in
      chick thymus caused by irradiation.

PMID- 8276441
TI  - Significance of monosynaptic and polysynaptic reflexes in neonatal rat spinal
      cord in vitro.
AB  - Stimulation of a dorsal root in an isolated spinal cord, elicited a monosynaptic
      reflex (MSR) in the corresponding ventral root at a latency of 3-5 msec and a
      dorsal root reflex (DRR) in an adjacent dorsal root 2-3 times the latency of MSR.
      The magnitude of DRR was 10 times smaller than the MSR. These reflexes could be
      decreased by the agents which suppress synaptic transmission e.g. either by
      decreasing the [Ca2+]0 or by increasing [Mg2+]0. In the absence of magnesium
      ([Mg2+]0) in the perfusing medium, the MSR was 15-20% greater in its magnitude
      and the segmental polysynaptic reflex (PSR) was distinctly seen at 8-10 msec
      latency. Segmental PSR disappeared when [Mg2+]0 ions are added to perfusing
      medium probably indicating the involvement of N-methyl-D-aspartate receptors.
      Further, in this preparation homosynaptic inhibition and pre- or post-synaptic
      inhibitions could be elicited. This preparation, thus serves as useful model for
      the study of central synaptic transmission to study the pharmacological or
      neurotoxic agents.

PMID- 8276442
TI  - Effect of exogenous dexamethasone and corticosterone on weight gain and organ
      growth in post-hatched white Leghorn chicks.
AB  - Induced chronic hypocorticalism by dexamethasone (DXM) and hypercorticalism by
      corticosterone (CORT) retarded body weight gain as well as the growth of spleen,
      bursa, liver, kidney and pancreas during the first month of development in male
      leghorn chicks. Adrenal weight was reduced by DXM and increased by CORT.
      Correspondingly, there were histological regressive changes in the cortex with a
      decreased cortico-medullary ratio with DXM treatment, while a reverse trend was
      there with CORT treatment. However, an increase in weight of testis and better
      organization of seminiferous cords and interstitium was observed in DXM treated
      chicks, and there was a decrease in weight and poor histological organization in
      CORT treated chicks. Both DXM and CORT induced stimulatory changes in thyroid
      denoted by increased epithelial cell height and decreased colloidal content.
      These observations indicate that corticosteroids have definite influence on post
      hatched growth and maturation of chicks.

PMID- 8276443
TI  - Modulation of feeding and drinking by dopamine in caudate and accumbens nuclei in
      rats.
AB  - Injection of dopamine (DA) into accumbens and caudate nuclei facilitates a dose
      dependent increase in food and water intake, whereas administration of spiperone
      (SP), a central D2-receptor antagonist suppresses DA-facilitated food and water
      intake. Bilateral lesions of nucleus accumbens and caudatus result in a sustained
      and significant decrease in food and water intake. The results suggest that DA is
      a neurotransmitter involved in feeding and drinking behavior in accumbens and
      caudate nuclei and this effect is mediated by central D2 receptors.

PMID- 8276444
TI  - Acute oral toxicity of insect repellent N,N-diethylphenylacetamide in mice, rats
      and rabbits and protective effect of sodium pentobarbital.
AB  - Median lethal dose (LD50) of undiluted liquid insect repellent N,N
      diethylphenylacetamide (DEPA) in male mice, rats and rabbits was 900, 825 and 635
      mg/kg respectively when administered by gavage. Signs of DEPA intoxication point
      to stimulation of central nervous system (CNS). Acetazolamide (10 mg/kg), sodium
      bicarbonate (40 mg/kg), and atropine (5 mg/kg) when injected (ip) 5 min after a
      lethal oral dose of DEPA (1700 mg/kg) did not prevent mortality, while sodium
      pentobarbital (SPB; 20 mg/kg) when injected 5 min after or 15 min before DEPA
      provided greater protection to the animals. SPB pretreatment elevated the LD50 of
      DEPA to 1780 and 1535 mg/kg in mice and rats respectively and 85% rats survived
      when SPB was injected 5 min after acute oral exposure to DEPA (1000 mg/kg).
      Carboxylesterase (CaE) inhibition is not a factor in the protection mechanism of
      SPB. DEPA (1000 mg/kg) when given orally elevated blood PCO2 and reduced pH, O2
      content and per cent O2 saturation, while administration of SPB after the same
      dose of DEPA reduced the degree of acidosis and raised PCO2, and increased the O2
      content and per cent O2 saturation to near normal status. The CNS depressant
      action of SPB may be a crucial factor in protection of rats from DEPA poisoning.

PMID- 8276445
TI  - Histomorphological changes in lung of rats following exposure to wood smoke.
AB  - Rats were exposed to repeated, intermittent exposure to smoke generated from
      combustion of 1g wood/15 min, total period for 75 min daily under dynamic
      exposure conditions, over a period of 15, 30 and 45 days. First 15 days exposure
      caused mild bronchiolitis, hyperplasia and hypertrophy of bronchiolar epithelial
      lining cells, some necrosed lining cells desquamated into lumens, congestion of
      parenchymatous blood vessels, oedema, hyperplasia of lymphoid follicles,
      peribronchiolar and perivascular infiltration of polymorphonuclear cells, and
      mild emphysema. These lesions progressed further during 30 and 45 days of
      exposure, though emphysematous changes remain constant. By 30 days and 45 days,
      hyperplastic and hypertrophic changes of bronchioles become quite marked, with
      mononuclear cells infiltration and alveolar septa thickening. Hematological
      studies show marginal alterations in hemoglobin levels, ESR, PCV and TLCS during
      15 days, where as significant changes in eosinophil were observed during 30 and
      45 days, and ESR during 45 days only. The results indicate progressive
      pathomorphological pulmonary lesions with subsequent exposure to wood smoke in
      controlled conditions.

PMID- 8276446
TI  - Detection of antibodies to serum IgA and IgG in peptic ulcer cases by indirect
      haemagglutination test.
AB  - Autoantibodies to serum IgA and IgG were detected in 206 peptic ulcer patients
      (196 duodenal ulcer and 10 gastric ulcer) and 52 healthy age and sex-matched
      controls by indirect haemagglutination test. A significantly increased mean titre
      of autoantibodies to serum IgA was observed in the peptic ulcer patients. Forty
      eight (24.61%) duodenal ulcer cases had autoantibody titre values above mean +/-
      2 SD of controls. Titres of autoantibodies to serum IgG were significantly
      increased only in the gastric ulcer cases. The results suggest an immunologic
      abnormality in a sizeable fraction of these cases.

PMID- 8276447
TI  - Production of monoclonal antibodies against equine influenza A/Equi-2 (H3N8)
      Indian isolate.
AB  - Seven hybrid cell lines of mouse myeloma cell line NSO and spleen cells of BALB/c
      mice producing monoclonal antibodies (MAbs) against equine influenza A/Equi
      2/Ludhiana/87 (H3N8) virus were developed. These MAbs were purified, isotyped and
      characterised by enzyme linked immunosorbent assay (ELISA), fluorescent antibody
      test (FAT), haemagglutination inhibition (HI) and virus neutralization (VN)
      tests. The titres of ascitic fluids induced by hybridomas as estimated by ELISA
      ranged from 1:25,600 to 1:51,200. Monoclonality of these clones was confirmed
      using a panel of 5 viral antigens, each belonging to a single isotype. MAbs (5)
      belonged to IgM and one each to IgG1 and IgG2a. Two epitopes appeared to be
      closely resembling by HI and VN tests but other two epitopes appeared to be
      different.

PMID- 8276448
TI  - Status of different immune cells during regression of a rat histiocytoma.
AB  - Status of CD4 and CD8 positive T-lymphocytes, natural killer cells and
      macrophages has been studied in animals which reject AK-5 histiocytoma. Analysis
      of immune cells which enter the tumour showed higher number of CD8 positive and
      NK cells around day 25 after tumour transplantation, suggesting their
      participation in tumour rejection.

PMID- 8276449
TI  - A new role for vitamin D: cholecalciferol promotes dermal wound strength and re
      epithelization.
AB  - Vitamin D endocrine system is a potent regulator of cell growth and maturation.
      Vitamin D3 modulates growth kinetics of many cells and produces divergent
      actions. Keeping this in view, cholecalciferol is evaluated for its actions on
      dermal wound healing in Wistar rats. Intraperitonial cholecalciferol at 5, 10, 15
      IU/g body weight doses produces increases in wound breaking strength and promotes
      epithelization significantly. Results suggest that there is some biological role
      for vitamin D endocrine system, ir wound repair. A clear understanding of this
      role of vitamin D3 may define new avenues in wound medication.

PMID- 8276450
TI  - Steroid hormones retard aflatoxin-induced cytotoxicity.
AB  - Protective effect of sex steroid hormones on aflatoxin-induced cytotoxicity on
      RBC (hemolysis) was examined in vitro. Addition of aflatoxin (2 micrograms/ml) in
      RBC suspension caused significant increase in hemolysis. Concurrent addition of
      aflatoxin (2 micrograms/ml) and estradiolbenzoate (100-1200 pg/ml) in RBC
      suspension significantly retarded aflatoxin-induced hemolysis. Similarly,
      addition of aflatoxin (2 micrograms/ml) along with testosterone propionate (5-60
      ng/ml) in RBC suspension retarded aflatoxin-induced hemolysis. Among the two
      synthetic hormones studied estradiolbenzoate was more potent than testosterone
      propionate.

PMID- 8276451
TI  - Effect of xylene, toluene and methyl alcohol on liver collagenesis in rats.
AB  - Among the three important industrial solvents used, maximum stimulation of
      collagen formation in rat liver was caused by methyl alcohol followed by toluene
      and xylene. A combined treatment also promoted collagenesis suggesting a
      synergistic effect of these solvents.

PMID- 8276452
TI  - Effect of methyl parathion on Na(+)-K+ and Mg2+ adenosine triphosphatase activity
      in developing central nervous system in rats.
AB  - Developing rat pups exposed to sublethal doses of methyl parathion exhibit marked
      alteration in the activities of Na(+)-K+ and Mg2+ ATPases. The results suggest
      that the first post natal week developing animals are more sensitive to
      organophosphorous insecticide compared to higher age group animals.

PMID- 8276453
TI  - Fetal H-2 odortypes are evident in the urine of pregnant female mice.
AB  - The major histocompatibility complex (MHC) imparts to each mouse an individual
      urinary odor, called "odortype", which reflects its MHC genotype. Perception of
      odortypes affects mate selection and embryonic implantation. Recent findings that
      odortypes are expressed as early as one day of age suggested that they might
      already be expressed in utero. We now report that at 9-12 days of gestation,
      odortypes specified by paternal (non-maternal) MHC haplotypes become apparent in
      maternal urine. Thus, odortypes are expressed in utero, can be sensed even before
      birth, and may serve in familial identification and communication.

PMID- 8276454
TI  - HLA supratypes in an Italian population.
AB  - A supratype analysis of a North Italian population was performed, using 16
      polymorphisms in the HLA region spanning the HLA-A-DP segment. Fourteen
      supratypes were identified, mostly corresponding to those found in other
      Caucasoid populations. The degree of their conservation both within the B-DR/DQ
      region and in the regions telomeric and centromeric from HLA-A and DP was
      evaluated and linkage disequilibria among several DR and DP alleles were
      identified. Notably, the degree of association with DP increased when the DR
      marker was part of a conserved B-DR/DQ supratype. These data are relevant to the
      definition of the genetic structure of the population and to the prediction of
      probabilities of histocompatibility matching between unrelated individuals.

PMID- 8276455
TI  - Sequence and expression pattern of the human MAGE2 gene.
AB  - We reported previously identification of the human MAGE1 gene, which encodes an
      antigen recognized on human melanoma MZ2-MEL by autologous cytolytic T
      lymphocytes. In addition to MAGE1, melanoma MZ2-MEL expresses several closely
      related genes, one of which has been named MAGE2. The complete MAGE2 sequence was
      obtained and it comprises 3 exons homologous to those of MAGE1 and an additional
      exon homologous to a region of the first MAGE1 intron. Like the open reading
      frame of MAGE1, that of MAGE2 is entirely encoded by the last exon. The MAGE1 and
      MAGE2 sequences of this exon show 82% identity and the putative proteins show 67%
      identity. The MAGE2 gene is expressed in a higher proportion of melanoma tumors
      than MAGE1. It is also expressed in many small-cell lung carcinomas and other
      lung tumors, laryngeal tumors, and sarcomas. No MAGE1 and MAGE2 gene expression
      was found in a large panel of healthy adult tissues, with the exception of
      testis.

PMID- 8276456
TI  - Hierarchy in the assembly of HLA-B27 and HLA-Cw3 molecules in transgenic mice.
AB  - Cell surface expression of human class I molecules in transgenic mice is
      dependent upon the available pool of beta 2-microglobulin (beta 2m) and the
      affinity between mouse beta 2m and human class I molecules. HLA-B27 and HLA-Cw3
      transgenes can be expressed in mouse strains of the H-2 haplotypes b, f, k, and s
      which encode two endogenous class I genes mapping to H-2K and H-2D. The human
      class I genes cannot be expressed on H-2d and H-2q haplotypes which encode three
      endogenous class I molecules (K,D,L). This suggests that there may be only enough
      mouse beta 2m molecules to support three class I molecules. When both the HLA-B27
      and HLA-Cw3 genes are introduced into H-2b mice, only HLA-Cw3 reaches the cell
      surface. This suggests that HLA-Cw3 has a higher affinity than HLA-B27 for mouse
      beta 2m. The possible implications of our findings regarding the assembly,
      transport, and expression of class I MHC molecules in vivo are discussed.

PMID- 8276457
TI  - Polymorphism detection and sequence analysis of human T-cell receptor V alpha
      chain-encoding gene segments.
AB  - The T-cell receptor (Tcr) provides specificity for antigen recognition by its
      variable domain, primarily consisting of two germline encoded variable (V) region
      gene segments. Thus it has been suggested that inherited polymorphisms in the
      TCRV gene segments could contribute to differential immune responsiveness (e.g.,
      autoimmunity) in human populations. In the present study, we have sought
      potentially functional polymorphisms in the germline TCRAV gene segments. Using
      denaturing gradient gel electrophoresis on polymerase chain reaction (PCR)
      amplified products from the pooled DNA of many individuals, we identified
      polymorphisms in the TCRAV2S1, AV4S1, AV7S1, and AV8S1 gene segments. A complete
      DNA sequence analysis of these PCR products identified polymorphisms that
      affected amino acids in the predicted antigen-binding regions of the Tcr alpha
      chain, as well as polymorphisms in the introns. Genotype analysis of all nine DNA
      point mutations showed a 5%-50% range (averaging 35%) of minor allele
      frequencies, often resulting in individuals homozygous for the alternate allele
      forms. All possible haplotype combinations of the amino acid-affecting
      polymorphisms were found, indicating that in human populations there are a large
      number of different germline haplotypes encoding V gene segment alleles. These
      TCRAV coding region polymorphisms provide the rationale for, and allow the direct
      testing of, hypotheses concerning inherited polymorphisms within the T-cell
      receptor genes that may contribute to autoimmune susceptibility.

PMID- 8276458
TI  - Comments on the detection of reciprocal recombination or gene conversion.

PMID- 8276459
TI  - Sequence and diversity of rat T-cell receptor alpha-chain-encoding genes.

PMID- 8276460
TI  - Cloning of cDNA coding for the rat mu heavy chain constant region: differences
      between rat allotypes.

PMID- 8276461
TI  - Nonhuman primate Mhc-DQA and -DQB second exon nucleotide sequences: a
      compilation.

PMID- 8276462
TI  - Heat shock proteins transfer peptides during antigen processing and CTL priming.
AB  - Recently emerging evidence indicates that the heat shock proteins (HSPs) gp96,
      hsp90, and hsp70 associate with antigenic peptides derived from cellular
      proteins. This evidence forms the basis of the following two hypotheses: 1) that
      HSPs constitute a relay line in which the peptides, after generation in the
      cytosol by the action of proteases, are transferred from one HSP to another,
      until they are finally accepted by MHC class I molecules in the endoplasmic
      reticulum, and 2) that the binding of peptides by HSPs constitutes a key step in
      the priming of cytotoxic T lymphocytes (CTLs) in vivo. The following chain of
      events is suggested: HSPs are released from virus-infected cells or tumor cells
      in vivo during lysis of cells during infection or by the action of antibodies or
      nonspecific effectors. The HSPs, which are now complexed with antigenic peptides
      derived from the cognate cells, are taken up by macrophage or other specialized
      antigen-presenting cells, possibly by a receptor-mediated mechanism. The HSP
      borne peptide is then routed to the endogenous presentation pathway in the
      antigen-presenting cell and is displayed in the context of that cell's MHC class
      I, where it is finally recognized by the precursor CTLs. Thus it is suggested
      that, as with antigen presentation by MHC class II molecules, presentation by MHC
      class I molecules is also carried out primarily by the host antigen-presenting
      cells. This mechanism explains the phenomenon of cross-priming and has
      implications for the development of immunological strategies against cancer and
      infectious diseases.

PMID- 8276463
TI  - Cloning and characterization of a cdc25 phosphatase from mouse lymphocytes.
AB  - Members of the cdc25 phosphatase family are proposed to function as important
      regulators of the eukaryotic cell cycle, particularly in the induction of mitotic
      events. A new cdc25 tyrosine phosphatase, cdc25M1, has been cloned from a mouse
      pre-B cell cDNA library and characterized. The cdc25M1 protein consists of 465
      amino acids with a predicted relative molecular mass (M(r)) of 51,750. Over the
      highly conserved carboxyl terminal region, the amino acid sequence similarity to
      the human cdc25 C or Hs1 isoform is 89%, while the overall similarity is 67%. The
      phosphatase active site is located within residues 367-374. Tissue expression of
      the cdc25M1 was highest in mouse spleen and thymus by northern blot analysis. The
      cdc25M1 mRNA was detected in a number of cloned mouse lymphocyte cell lines
      including both CD8+ and CD4+ cells. cdc25M1 mRNA was shown to be cell cycle
      regulated in T cells following interleukin-2 (IL-2)-stimulation. Accumulation of
      cdc25M1 mRNA occurred at 48 h after IL-2 stimulation, when lymphocytes were
      progressing from S phase to G2/M phase of the cell cycle. This pattern of
      expression is in contrast to that observed for other protein tyrosine
      phosphatases expressed in T lymphocytes including CD45, LRP, SHP, and PEP. The
      elevation in cdc25M1 mRNA level occurred concomittant to the appearance of the
      hyperphosphorylated form of p34cdc2 protein kinase. A purified, bacterial
      expressed recombinant cdc25M1 phosphatase domain catalyzed the dephosphorylation
      of p-nitrophenol phosphate, as well as [32P-Tyr] and [32P-Ser/Thr]-containing
      substrates. Preincubation of p34cdc2 kinase with cdc25M1 activated its histone H1
      kinase activity in vitro. These results suggest that cdc25M1 may be involved in
      regulating the proliferation of mouse T lymphocytes following cytokine
      stimulation, through its action on p34cdc2 kinase.

PMID- 8276464
TI  - Upmodulation by estrogen of HLA class I expression in breast tumor cell lines.
AB  - The expression of major histocompatibility complex (MHC) class I antigens was
      studied in five breast carcinoma cell lines before and after treatment with 17
      beta estradiol. Increased HLA class I antigen expression correlated with the
      presence of estrogen receptors. The modulation of expression appeared to be
      mediated by transcriptional mechanisms, as revealed by class I mRNA levels. To
      elucidate the basis of MHC class I upregulation, we examined transcriptional
      factor binding activity to the class I regulatory element (CRE). Our results
      showed that 17-beta estradiol induced increases in factor binding activity to the
      CRE II probe, and decreases to the CRE I probe. In addition, our results
      suggested that factors that bind the CRE I region may modulate the binding of CRE
      II. Binding to CRE II was significantly increased in extracts pretreated with a
      competitor that contained the CRE I sequence, and that bound NF-kB/kBF1. In
      addition, induction of NF-kB binding activity by the tumor necrosis factor was
      accompanied by a decrease in nuclear factors that bind to the CRE II region.

PMID- 8276465
TI  - DNA sequences specific for Caucasian G3m(b) and (g) allotypes: allotyping at the
      genomic level.
AB  - Assignment of the G3m(g) and (b) correlative amino acid residues was performed at
      the genomic level by direct sequencing of DNA from nine Caucasian individuals.
      Two oligonucleotide primers were used for subclass-specific enzymatic
      amplification of a DNA segment comprising a major portion of the second and third
      constant region domains (CH2 and CH3) of the human IgG3 heavy chain gene.
      Comparison of the sequences of amplified DNA from individuals serologically typed
      as homozygous for G3m(b) or G3m(g) or as heterozygous, G3m(b,g), revealed
      differences in the codons for the amino acid residues 291, 296, and 384. Proline,
      phenylalanine, and serine at these positions corresponded to G3m(b), and leucine,
      tyrosine, and asparagine to G3m(g). Heterozygotic individuals, typed G3m(b,g),
      displayed both the G3m(b) and G3m(g) codons at these three positions. The
      polymorphism at each of these three codons could be identified either as the
      appearance, or the loss, of recognition sites for the two restriction
      endonucleases, Nsp BII and Rsa I. This allowed the development of a polymerase
      chain reaction (PCR)-based assay permitting the distinction of G3mb and G3mg
      alleles by analyzing the electrophoretical mobility of the DNA fragments
      generated by digestion of the PCR-products with Nsp BII and Rsa I.

PMID- 8276466
TI  - Cloning of a new kinesin-related gene located at the centromeric end of the human
      MHC region.
AB  - We previously reported the presence of a new gene (HSET) with an unknown
      function, in the centromeric side of the class II gene region of the human major
      histocompatibility complex (MHC). cDNA clones corresponding to the HSET gene were
      isolated from a human testis cDNA library. A 2.4 kilobase transcript from the
      HSET gene was abundantly expressed in testis, B-cell, T-cell, and ovary cell
      lines but was not detected in lung or stomach. Analysis of the nucleotide
      sequence of the HSET cDNA clones revealed significant similarity to kinesin
      related proteins in yeast, Drosophila, and human. Its predicted amino acid
      sequence contains a domain with strong sequence similarity to the ATP-binding and
      motor domains of a plus end-directed microtubule motor protein, kinesin, which
      might be involved in mitotic chromosome segregation, suggesting that the HSET
      gene encodes a novel kinesin-related protein.

PMID- 8276467
TI  - Comparative analysis of sequence variability in the upstream regulatory region of
      the HLA-DQB1 gene.

PMID- 8276468
TI  - Natural killer lectin-like receptors have divergent carboxy-termini, distinct
      from C-type lectins.

PMID- 8276469
TI  - Nucleotide sequence of HLA-B*2706.

PMID- 8276470
TI  - Exocrine differentiation of trichoepithelioma & desmoplastic trichoepithelioma; a
      scanning electron microscopic study.
AB  - Trichoepithelioma is widely thought to be a benign appendage tumour which arises
      from hair follicles (i) Scanning electron microscopy reveals that the basement
      membrane of Trichoepithelioma & desmoplastic Trichoepithelioma is similar to the
      basement membrane of exocrine glands like sweat or sebaceous gland. The basement
      membrane of Trichoepithelioma and desmoplastic Trichoepithelioma do not show any
      difference in their structure. Thus, possibly Trichoepithelioma and desmoplastic
      Trichoepithelioma arises from exocrine gland and are closely related to each
      other.

PMID- 8276471
TI  - Incidence of fungal infection in extra hepatic biliary stone disease.
AB  - 50 patients undergoing biliary surgery were studied to know the incidence of
      fungal infection. Samples such as bile & stones for mycological analysis were
      obtained from the gall bladder & Common Bile Duct (CBD) at the time of surgery.
      Fungal aetiology was established in 8 (16.3%) cases. Incidence of fungal
      infection was more (12.2%) in gall bladder bile as compared to 6% in common bile
      duct bile. The nucleus of stone yielded growth of fungus in only 2 (4.6%) cases.
      Candida albicans, C. tropicalies, C, kruzei, Penicillium and Aspergillus were the
      common fungal isolates in the present study.

PMID- 8276472
TI  - Growing incidence of cutaneous and ungual infections by non-dermatophyte fungi at
      Jabalpur (M.P.).
AB  - A random survey of skin and nail infections was done at Jabalpur (M.P.). Out of
      the 80 suspected cases 60 were culture positive. Out of these 25 were of
      dermatophyte infection followed by 21 cases of phaeohyphomycosis, 7 of
      aspergillosis, 4 of hyalohyphomycosis, 2 of mixed infection in which a non
      dermatophyte was associated with a dermatophyte and 1 had yeast infection.
      Trichophyton rubrum was the only dermatophyte isolated. Among the non
      dermatophyte infections cases of Alternaria chlamydospora, Cladosporium sphaero
      spermum, Curvularia senegalensis, Chaetomium globosum, Scopulariopsis brumptii,
      Paecilomyces variotii and Aspergillus chevalieri are for the first time
      documented as etiologic agent of cutaneous and ungual mycosis from India.

PMID- 8276473
TI  - Urine culture sensitivity pattern in a private laboratory setup.
AB  - During a two year study period, 6163 samples of urine among a total of 10366
      miscellaneous samples received for culture, were analysed. Of these 1488 samples
      (24.15%) showed evidence of infection. In our study, E. Coli was found most
      frequently (61.40%) followed by Klebsiella (17.1%). The pattern of antibiotic
      sensitivity was analysed. Ciprofloxacin and Norfloxacin proved to be the most
      promising among the new generation of antibiotics. Results with Cloxacillin,
      Colistin and Lincomycin were found to be disappointing. The study serves to
      analyse the pattern of urinary infection in our setup and also dwells upon the
      emergence of strains resistant to even the newer antibiotics.

PMID- 8276474
TI  - Bacteriology of peritoneal fluid in paediatric surgical emergencies.
AB  - This study deals with the incidence of aerobic and anaerobic organisms of the
      peritoneal fluid of 60 consecutive children subjected to emergency celiotomy. Two
      thirds of the cases were below the age of year. Peritoneal fluid was collected
      immediately after entering the peritoneal cavity and inoculated both for aerobic
      an anaerobic cultures. Bacterial growth occurred in 34 (57%) of the specimens.
      Anaerobic bacteria alone grew in 3 (5%) of the specimens, aerobes alone in 22
      (37%) of specimens. A mixed aerobic and anaerobic bacteria grew in 9 (15%) of the
      specimens. There were 44 aerobic and 19 anaerobic isolates. All anaerobes were
      sensitive to metronidazole while most of the aerobes were sensitive to
      gentamycin. Culture was positive in 20 out of 42 (47.6%) specimens, where the
      peritoneal fluid was clear and there was no evidence of peritoneal contamination
      at the time of surgery.

PMID- 8276475
TI  - Evaluation of cellular immunity in diabetic uraemics by cutaneous response to
      recall antigens and 2:4 dinitrochlorobenzene and T-cell rosette formation.
AB  - Twenty diabetic uraemics and twenty two healthy matched controls comprised the
      material for this study. Cell mediated immunity was assessed by estimation of T
      cell rosette percentage and cutaneous response to recall antigens--purified
      protein derivative, candida antigen and 2:4 dinitrochlorobenzene. Results
      analysis revealed depressed cell mediated immunity in diabetic uraemics in the
      form of impaired cutaneous response to recall antigens and reduction in T cell
      rosette percentage, in comparison to controls.

PMID- 8276476
TI  - Invasive thymoma: cytomorphological features on fine needle aspiration cytology.
AB  - Although thymomas are the commonest neoplasms of the anterior mediastinum,
      distinction between benign and malignant thymomas is controversial on Fine needle
      aspiration biopsy. We present cytomorphological features of a case of invasive
      thymoma on computed tomographic guided fine needle aspiration cytology and its
      basis is discussed in light of current concepts of thymic tumours.

PMID- 8276477
TI  - Evaluation of particle agglutination test for detection of HIV-I antibodies.
AB  - A commercially available particle agglutination test (PA) was evaluated for its
      specificity and sensitivity as compared to ELISA currently used in our laboratory
      to detect HIV-I antibodies. A total of 463 sera from blood donors and clinical
      referrals were screened by PA, 45 were found to be positive (9.7%). Out of 463,
      258 sera were simultaneously screened by ELISA; 28 were found to be positive
      (10.8%). Twelve samples showing positive results by both ELISA & PA were tested
      by Western blot and were confirmed to be positive. We found sensitivity of PA as
      compared to ELISA as 100% and specificity to be 88.44%. Readings of PA taken at 2
      hrs should be reconfirmed at 24 hrs as it eliminates a number of false positives.
      Overall, we feel PA is fairly comparable with ELISA. It can be used in the set up
      where equipment and trained personnel for ELISA are not available for primary
      screening purposes.

PMID- 8276478
TI  - Blood transfusion services in Delhi.
AB  - In 1991, approximately 40% of total blood requirement in Delhi was collected from
      commercial blood donors. The rest was supplied by voluntary and replacement
      donations in hospital-based blood banks and by voluntary blood recruiting agency
      (Indian Red Cross Society). This study analyses the standards of working and
      quality assurance in 26 blood transfusion centers in Delhi. The majority of these
      centers are ill-equipped and lack trained manpower. Most of these do not have
      adequate testing facilities and any standardized procedure for blood collection.
      Quality assurance scheme is not being followed and documentation and record
      maintenance is grossly inadequate. This reports also gives the recommendations
      for improvements of blood transfusion services in Delhi.

PMID- 8276479
TI  - Benign cystic teratoma of mesentery.
AB  - Benign cystic teratomas are the commonest germ cell tumors in gonads but are rare
      in extragonadal sites and very rare in the mesentery. Herein is reported a case
      of primary benign cystic teratoma of the mesentery in a 10 year old girl.

PMID- 8276481
TI  - Angiolymphoid hyperplasia with eosinophilia (Kimura's disease).
AB  - Angiolymphoid hyperplasia with eosinophilia (AHE) is a rare disease entity which
      usually presents as subcutaneous nodules, sometimes simulating lymphadenopathy or
      even angiosarcoma. We present here the histopathological aspects of a case which
      manifested as a subcutaneous forehead nodule, along with the relevant review of
      literature concerning this rare entity.

PMID- 8276480
TI  - Live male adult Loaloa in the anterior chamber of the eye--a case report.

PMID- 8276482
TI  - Alveolar microlithiasis--report of two cases.

PMID- 8276483
TI  - A report on the isolation of Leptospira icterohaemorrhagiae serovar from man.

PMID- 8276484
TI  - Blood safety.

PMID- 8276485
TI  - Science challenging HIV infection.

PMID- 8276486
TI  - Multidrug resistant Salmonella typhi in India.

PMID- 8276487
TI  - Granulomatous angitis of central nervous system.

PMID- 8276488
TI  - Better safe than sorry.

PMID- 8276489
TI  - Remembering Paracelsus (1493-1541)

PMID- 8276490
TI  - Successful pregnancy with reduced ovarian mass in the rat.
AB  - This paper reports the successful pregnancy in rats with only 10-20% of ovarian
      tissue. Sprague-Dawley female rats of breeding age were divided into five groups:
      group 1 (completely ovariectomized), the ovaries from both the sides of the rats
      were removed completely; group 2 (partially ovariectomized, 80-90% of the ovary
      of each side was removed leaving the remaining tissue in place; group 3
      (ovariectomized with flank transplant), the ovary of each side was removed from
      the ovarian stalk and inserted into a subcutaneous pocket made surgically in the
      flank on the respective side of the same rat; group 4 (partially ovariectomized
      with flank transplants), 80-90% of the ovarian mass was removed from the ovarian
      stalk and put back in the flank position in the subcutaneous pocket on the same
      side; group 5 (control), rats with intact ovaries. Estrous cyclicity, mating
      behavior and pregnancy rate were recorded in the animals. Percent rats cycled
      were 0.00, 80.00, 80.00, 70.00 and 100 in groups 1-5 respectively; percent cycled
      rats mated were 86.27, 100, 71.42 and 100 in groups 2-5 respectively; and percent
      mated rats reaching successful pregnancy were 36.36, 0.00, 100 and 100 in groups
      2-5 respectively. Pregnancy rate in the mated rats in group 2 was lower than that
      of groups 4 (P < 0.01) and 5 (P < 0.01), whereas, it did not differ among groups
      4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276491
TI  - Altered maternal thyroid function: fetal and neonatal heart cholesterol and
      phospholipids.
AB  - The influence of maternal thyroid function on the fetal and neonatal myocardial
      cholesterol and phospholipid content was studied in rats. Fetuses born to
      hyperthyroid mothers had decreased total cholesterol and increased esterified
      cholesterol while offsprings born to hypothyroid mothers had increased total,
      free and esterified cholesterol during late gestation and/or at term.
      Phospholipid fractions phosphatidyl choline and phosphatidyl ethanolamine in
      offsprings born to hyperthyroid mothers were not significantly changed.
      Offsprings born to hypothyroid mothers had decreased total phospholipids,
      phosphatidyl choline and phosphatidyl ethanolamine at fetal and neonatal stages.
      3H-acetate incorporation in phosphatidyl choline and phosphatidyl ethanolamine
      was also decreased. Maternal thyroid seems to have important role in the
      regulation of cholesterol and phospholipid metabolism in fetal and neonatal
      hearts.

PMID- 8276492
TI  - Endothelin-1 and carbachol: differences in contractile effects and myosin
      phosphorylation in lamb tracheal smooth muscle.
AB  - Endothelin-1 is a new potent vasoconstrictor peptide produced by the endothelial
      cells. The contractile effects of endothelin-1 (ET-1) were compared with those of
      cabachol in lamb tracheal smooth muscle. Equimolar concentrations (10(-6)M) of
      endothelin 1 and carbachol elicit rapidly rising isometric tension which is
      maintained indefinitely in a steady state when fibres are stimulated with
      carbachol. Fibre strips exposed to ET-1 cannot maintain peak isometric force
      beyond 15-20 min and instead these exhibit a decline in tension towards near
      relaxed state. In addition to an early transient relaxation, ET-1 stimulation
      results in a 20,000 Da myosin light chain phosphorylation pattern different from
      that of carbachol stimulation.

PMID- 8276493
TI  - GABA B mediated analgesia in tonic pain in monkeys.
AB  - The present study was designed to characterise the analgesia produced by the GABA
      B agonist baclofen in tonic pain in monkeys. The effect of various doses of
      baclofen was studied on formalin induced pain. Baclofen was injected
      intraperitoneally 30 min prior to formalin injection in five doses of 2, 4, 6, 8,
      and 10 mg/kg and the pain was quantified for a period of one hour. Baclofen
      produced dose related analgesia, 6 mg/kg having maximal effect. The
      antinociceptive effect of baclofen could be attributed to the effect of baclofen
      on GABA B receptors producing presynaptic inhibition of primary nociceptive
      afferents in the dorsal horn of the spinal cord.

PMID- 8276494
TI  - Praziquantel therapy in neurocysticercosis.
AB  - Neurocysticercosis is being recognised more often now, because of advances in
      radio-imaging. No treatment was available for this disease till about a decade
      back. Praziquantel has provided new hope. From India, there are very few
      published reports on experience with this drug. Nine cases of neurocysticercosis
      are being presented, where praziquantel therapy has been tried. Five patients
      with tumour syndrome and one patient with a meningoencephalitic syndrome have
      shown a favourable response. In 3 patients with epilepsy syndrome, it is
      difficult to assess the role of this drug in their management. The relevant data
      have been presented and analysed.

PMID- 8276495
TI  - Enhanced Na-K ATPase activity in the aorta may explain the unaltered contractile
      responses to KCl in diabetes mellitus.
AB  - Sodium-potassium ATPase activity and transmembrane calcium influx in the aortic
      smooth muscle from control and diabetic rats were assessed indirectly through the
      measurement of KCl relaxation and contractile responses to CaCl2 in attempts to
      explain the contractile responses to KCl following streptozotocin-induced
      diabetes mellitus. There were no significant changes in the maximum contractile
      responses of the aortas from 4 and 12 week diabetic rats to KCl even when
      significant increases in calcium influx were demonstratable. On the other hand,
      the diabetic aortas were significantly (P < 0.05) more sensitive to KCl-induced
      relaxations than the controls. This provides an indirect evidence for increased
      activity of the sodium-postassium ATPase enzyme in the aortas from streptozotocin
      diabetic rats. This may, atleast in part, explain the inability of KCl to produce
      greater than normal contractions of the aortas from diabetic rats.

PMID- 8276496
TI  - Behavioural and biochemical changes produced by repeated oral administration of
      the insecticide endosulfan in immature rats.
AB  - In order to study the response of rats to repeated administration of the
      insecticide, endosulfan during the period of growth to maturity, food intake,
      body weight gain, Spontaneous Motor Activity (SMA) and Muscle Coordination (MC)
      were determined at regular intervals in male immature Wistar rats treated with a
      tolerated dose of (2 mg/kg/day) orally for 90 days. Twenty-four h after the
      termination of the treatment, organ weight and protein concentrations were
      determined. The convulsive action of picrotoxin (4 mg/kg, ip) was tested in
      another endosulfan-treated group. Food consumption and body weight gain decreased
      parallely. No changes occurred in the body tissues but for liver which was
      enlarged and its protein, glutamic oxaloacetic transminase and glutamic pyruvic
      transaminase concentrations increased. The MC was unaffected. A stimulation of
      SMA occurred several days (75-90) after commencing treatment and these animals
      responded greatly than control animals to the convulsive action of picrotoxin.
      These findings indicated that although endosulfan produced anorexia, there were
      no signs of undernourishment and motor impairment in these animals. Its toxic
      action were confined chiefly to the liver and central nervous system.

PMID- 8276497
TI  - Autonomic functions and audiovisual reaction time in heroin addicts.
AB  - Radial pulse rate, systolic BP (SBP), diastolic BP (DBP), initial GSR0), GSR
      after 5 minutes of relaxation (GSR5), auditory reaction time (ART) and visual
      reaction time, (VRT) were measured in 30 male heroin addicts and compared with 25
      male control subjects of similar age group. In heroin addicts DBP was
      significantly low (71.73 mmHg +/- 7.42, P < 0.05); while SBP although being low
      (106.13 mmHG +/- 10.08) was not significant. However, radial pulse was
      significantly higher. GSR0 was significantly higher (P < 0.001) but GSR5 was not
      significantly higher in these addicts, suggesting less sympathetic activity. In a
      separate group of ten heroin addicts effect of change in posture from supine to
      erect on BP was studied. This did not produce any rise in SBP or DBP at 1 and 2
      min, suggesting probably inhibition of baroreceptor reflex. Auditory reaction
      time (ART) and visual reaction time (VRT) were significantly prolonged (P < 0.001
      for each) in addicts, indicating deterioration of processing capability of CNS,
      or poor sensory-motor performance, or both.

PMID- 8276498
TI  - Monitoring the adverse profile of atenolol--a collaborative study.
AB  - Atenolol, a cardio selective beta-adrenergic blocker, frequently prescribed in
      various cardiac ailments, has not been thoroughly investigated for its adverse
      reaction profile in Indian patient. The present ADR monitoring study which was
      open, prospective and collaborative was therefore planned. A total of 440
      patients with various heart disease were enrolled after a strict inclusion and
      exclusion criteria from Maulana Azad Medical College, New Delhi and J.N. Medical
      College, Aligarh. fifteen patients dropped out leaving 435 for final analysis.
      Cold extremities occurred in 1.18% headache and dizziness in 1.41% breathlessness
      in 0.94% oedema in 0.70% and bradycardia in 0.47%. Adverse drug reaction in our
      study were less than those reported from Western countries. Better patient
      selection, optimal dose could have reduced the frequency of ADR in the present
      study. Racial factor and season might be operating to bring down ADR to atenolol
      in Indian patients.

PMID- 8276499
TI  - Effects of enalapril, an ACE-inhibitor, on bronchial responsiveness in
      asthmatics.
AB  - To assess the effects of enalapril on bronchial responsiveness, we studied ten
      stable asthmatics and five healthy normal volunteers. Spirometry and methacholine
      bronchoprovocation dose (PC20) were measured before and after oral administration
      of 20 mg enalapril. Significant hypotensive effect was observed in all. More than
      two fold (2.73) increase in bronchial responsiveness was observed in the
      asthmatics (P < 0.01) without significant change in the expiratory flows. PC20
      after enalapril fell by 56.8 +/- 23.0% of baseline value (P < 0.001). No
      significant change was observed in spirometric parameters and bronchial
      responsiveness in normal subjects. We conclude that enalapril significantly
      enhances BR and cannot be used safely in treatment of hypertension in asthmatics.

PMID- 8276500
TI  - Effect of ammonia, urea and diammonium phosphate (DAP) on lung functions in
      fertilizer plant workers.
AB  - A spirometric study (FVC, FEV1 & PEFR/Min) was carried out in workers exposed to
      fertilizer chemicals (91) as a whole, out of which 31 were Ammonia, 30 Urea and
      30 DAP plant workers, and 68 were controls belonging to the same age, sex, body
      surface area and socio-economic status. This study showed significant reduction
      in both PEFR/min and FEV1, the reduction being more in PEFR/Min., seems to
      indicate obstructive type of lung changes affecting the larger air-ways first,
      followed by bronchospasm. But FVC showed a significant reduction only after more
      than 10 years of exposure, probably causing restrictive changes only after
      prolonged exposure. Out of the 3 chemicals, DAP affected all the 3 parameters
      most, followed by Ammonia and Urea affected the least.

PMID- 8276501
TI  - Body composition, cardiovascular endurance and anaerobic power of yogic
      practitioner.
AB  - Forty male high school students, age 12-15 yrs, participated for a study of yoga
      in relation to body composition, cardiovascular endurance and anaerobic power.
      Ths Ss were placed into two subsets viz., yoga group and control group. Body
      composition, cardiovascular endurance anaerobic power were measured using
      standard method. The duration of experiment was one year. The result of ANCOVA
      revealed that a significant improvement in ideal body weight, body density,
      cardiovascular endurance and anaerobic power was observed as a result of yoga
      training. This study could not show significant change in body fat (midaxillary),
      skeletal diameters and most of the body circumferences. It was evident that some
      of the fat-folds (tricep, subscapular, suprailiac, umbilical, thigh and calf) and
      body circumferences (waist, umbilical and hip) were reduced significantly.

PMID- 8276502
TI  - The effect of aspirin, paracetamol and analgin on pharmacokinetics of
      chloroquine.
AB  - The effect of Aspirin, paracetamol and analgin on the kinetic profile of a single
      oral dose of chloroquine was studied in 8 healthy subjects. Aspirin did not alter
      the kinetic parameters of chloroquine whereas paracetamol and analgin
      significantly enhanced the Cmax and AUC0-alpha of chloroquine (P < 0.01, < 0.05
      respectively).

PMID- 8276503
TI  - Unwanted effects of ciprofloxacin in Indian population.
AB  - The present study was an attempt to evaluate epidemiological profile of adverse
      reactions of ciprofloxacin and factors influencing them in Indian population. The
      study was conducted in indoor patients of All-India Institute of Medical
      Sciences, New Delhi. The patients were in the age group of 21-65 years.
      Gastrointestinal upsets (nausea, vomiting, abdominal discomfort), headache,
      dizziness and skin rash were observed. Route of administration influenced the
      onset of ADRs. Severity of ADRs was proportional to dose. All reactions were
      reversible and the incidence of ADRs is lower in Indian population as compared to
      USA(1) but higher than seen in Japanese (2).

PMID- 8276504
TI  - A study on withdrawal related haemodynamic response in chronic propranolol
      treated conscious rats.
AB  - Single dose of propranolol hydrochloride (5 mg/kg, i.p.) caused significant fall
      in heart rate (HR) but not in systolic blood pressure (SBP) in normotensive
      conscious rats. Multiple doses of propranolol (5 mg/kg, i.p., twice-a-day for 5
      wk) caused significant fall in both HR and SBP at 2 wk and 4 wk in normotensive
      conscious rats. Sudden withdrawal of propranolol at 5 wk caused a significant
      blood pressure upswing and tachycardia between 12-24 h followed by normalization
      of both blood pressure and heart rate. The study documents a possible model of
      rebound hypertension in normotensive conscious rats.

PMID- 8276505
TI  - Modification of tricyclic antidepressant analgesia by calcium channel blockers.
AB  - The influence of calcium channel blockers (CCB) on the analgesic activity of
      tricyclic antidepressants (TCA) was examined using hot plate (thermal) and
      writhing (chemical) method. Intraperitoneal injections of TCA, imipramine and
      amitriptyline or CCB viz: verapamil, nifedipine, nicardipine and cinnarizine per
      se produced analgesia. The Analgesic effect of TCA was further enhanced by prior
      treatment with CCB. The increase in TCA analgesia could not be ascribed to
      unitary mechanism but could possibly be mediated by opioid and/or nonopioid
      systems. These results clearly provide an evidence that a combination treatment
      of CCB and TCA may permit reduction of the TCA doses while treating chronic pain
      of organic origin.

PMID- 8276506
TI  - Effect of cimetidine on adenohypophysis of male albino mice under certain
      experimental condition.
AB  - Effect of 75 mg/kg of body weight of cimetidine administered intraperitoneally
      daily for 14 days to two groups of experimental animals (one of the experimental
      group was having intact testis and another group was bilaterally orchidectomized)
      was observed on cell population & cell volume of gonadotrophs and lactotrophs in
      pituitary gland, as it has not been studied earlier. In the experimental group of
      intact testis, there was significant reduction in the cell population of FSH
      cells in the cephalomedian area (P < 0.001) and in the lateral lobe (P < 0.01);
      the volume of both FSH and LH cells was also significantly reduced. In group 4
      and group 5 there was significant increase in the population of lactotrophs and
      also in the volume of LH cells, FSH cells & lactotrophs. The change in the
      gonadotrophs in group 2 was due to increased production of testosterone from
      hypertrophied Leydig cells of testis rather then it's direct effect on
      adenohypophysis; in group 4 and group 5 the changes were due to lack of
      testosterone as in those cases bilaterally orchidectomy already done.

PMID- 8276507
TI  - Infraadditive diuretic efficacy of concurrent aminophylline and frusemide.
AB  - Male albino rats weighing between 150-225 gm fasted over night but freed having
      water ad libitum were used to assess the diuretic efficacy of intramuscular
      aminophylline and frusemide separately and concurrently after intraperitoneal 10
      ml of distilled water loading. The normal rate of diuretic weight loss was less
      augmented by aminophylline and more augmented by frusemide. The diuretic response
      was more by the concurrent intramuscular administration of aminophylline and
      frusemide in comparison with that due to either drug alone. However, the observed
      diuretic response of the two drugs administered concurrently was lesser
      (infraadditive) than the sum of the individual diuretic response (additive).

PMID- 8276508
TI  - Adverse reactions associated with aminopenicillins in Indian population.
AB  - The overall incidence of adverse drug reactions following ampicillin and
      amoxicillin administration to 439 and 169 indoor patients of All India Institute
      of Medical Sciences, New Delhi were 19.13% and 15.5% respectively. Ampicillin
      produced diarrhoea (7.74%), nausea and vomiting (7.74%) anorexia (5.46%) headache
      (4.10%) and allergic reactions (2.9%). With amoxicillin, anorexia was observed in
      4.79%, epigastric distress in 5.9% headache in 6.58%, coating of tongue in 8.98%
      and dizziness in 1.79% of patients. Intramuscular route of administration of
      ampicillin produced least ADRs. Females were more susceptible to adverse
      reactions of ampicillin and males to amoxicillin. Incidence of ADRs by these two
      aminopenicillins is less than that reported from abroad.

PMID- 8276509
TI  - Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats
      exposed to sarin aerosols.
AB  - The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on
      dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols.
      Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg,
      i.m.) did not significantly alter the parameters of the dynamic pulmonary
      mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min)
      depressed the respiratory rate, air flow and minute volume and enhanced the
      transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min
      prior to sarin exposure significantly modified or counteracted the above induced
      changes. It is concluded that the protective effect of carbamates is mainly due
      to the correction of respiratory changes caused by sarin aerosols in rats.

PMID- 8276510
TI  - Effect of Abana and Metoprolol on serum lipid profile in rabbits fed
      hyperlipidemic diet.

PMID- 8276511
TI  - Efficacy of calcium channel blocker as an adjunct in therapy of organophosphate
      poisoning.

PMID- 8276512
TI  - Blood in non-perfused lungs.

PMID- 8276513
TI  - Effect of organic and inorganic mercury on serum total and perchloric acid
      soluble sialic acids in rats.

PMID- 8276514
TI  - Survey of amalgam and composite restorations in Korea.
AB  - A small scale survey amongst general dental practitioners in Korea aimed to
      discover the reasons for placement or replacement of restorations. Material used
      and cavity type were recorded as was the age of restorations to be replaced,
      where known. Comparisons with data from the USA, Scandinavia, the UK and Italy
      provide the basis for observations on the reasons for longevity of restorations.

PMID- 8276515
TI  - Dental underemployment: a study of uncontrolled dental manpower immigration.
AB  - In the 1980s three studies were conducted in Israel utilising different methods
      of dental manpower evaluations. All identified a large future surplus of
      dentists. The current study re-evaluates the manpower supply and discusses
      possible solutions. A random sample of 800 dentists was approached by three
      mailings and a telephone call follow-up with a response of 49.7 per cent. Almost
      90 per cent of dentists reported an undersupply of patients, with a mean working
      load of 26.3 hours/week, but being willing to add up to 3.4 working hours/week.
      The oversupply of dentists has been dramatically affected by the addition of
      almost 1000 dentists who emigrated to Israel in 1991-92. To prevent a significant
      unemployment rate among dentists and an uncontrolled free market, it is urgently
      suggested for the benefit of both provider and consumer that; the demand for
      services be increased and additional financing of dental care be made available,
      that the total number of dentists be decreased by various measures and that their
      geographical distribution be improved. If necessary limits should be placed on
      the number of practices or the number of patients permitted per practice.

PMID- 8276516
TI  - The new professional role of the dentist under aspects of internal medicine.
AB  - There is a duty to provide oral health care for patients with special needs.
      Preventive dental care is crucial in this group of patients. Operative care is
      usually straightforward under local analgesia unless there is a bleeding
      tendency. Nevertheless, a medical history and examination of at least the face,
      neck and hands is mandatory and this should be re-checked before any surgical
      procedure. This paper reviews the management of patients with medical problems
      relevant to dentistry.

PMID- 8276517
TI  - Imaging: new versus traditional technological aids.
AB  - Until recently film has been the only medium on which to register radiographic
      images. Despite tremendous increase in sensitivity, the most sensitive films
      available at present still have a higher resolution than the eye, although at the
      cost of a more grainy image. Film speed for intraoral films seems to have reached
      its maximum unless a lower quality is accepted. Other methods, well established
      in medicine, like digital radiology, teleradiography and picture archiving and
      communication systems have started to make inroads into dentistry. In 1987 the
      first intraoral sensor and display processing unit, with the x-ray image on a
      television monitor, became available as an alternative to conventional
      radiography. Since then the sensors have improved enabling digital post
      processing to enhance details of interest for different diagnostic problems. A
      dose reduction of approximately 80 per cent compared to D-speed films can be
      obtained. The sensitive area of the sensor is still relatively small compared to
      conventional films, resulting in difficulties in positioning it. However new
      systems approach the image quality of conventional E-speed film. Instant
      availability of the images is a major attractive benefit of these new
      technologies. With the arrival of direct digital acquisition of maxillofacial
      radiographs an 'electronic office' is needed to derive the full benefit from this
      technology, including local and distant image transfer. Digital imaging in
      dentistry is presently still in a relatively primitive state although it is
      anticipated that by the middle of this decade considerable improvement will have
      been achieved making digital image equipment feasible for the general
      practitioner.

PMID- 8276518
TI  - Clinical testing--has it proved the efficacy of adhesives?
AB  - This paper examines the results of clinical trials on dentine adhesives, and
      discusses reasons why conflicting results are often reported. The age of the
      patient is probably the main factor in adhesive efficacy, and a higher loss rate
      of restorations is evident in older patients due to the nature of the dentine and
      relatively more tooth deformation during function.

PMID- 8276519
TI  - Oral health needs of the elderly--an international review. Commission of Oral
      Health, Research and Epidemiology Report of a Working Group.
AB  - There has been no significant evaluation of the oral health of the elderly on a
      global or regional basis. As a result of this deficiency in information a working
      group of the FDI was instituted in 1988. A questionnaire was developed and sent
      to 44 consultants and 53 national dental associations. Replies were recorded from
      31 countries while another 10 countries reported that they had no data on their
      ageing populations. Most of the replies were from the so-called western
      industrialised countries and these countries had some data on issues such as life
      span at birth, life span at 60, dental utilisation data and edentulousness.
      Beyond these areas data was not representative and scarce. Recommendations are
      that studies of this size tend not to be very productive and should not be
      replicated. In the agrarian societies where caries rates in children are still
      low, preventive services need to be introduced as well as palliative services. In
      the industrialising countries where caries rates are increasing, the emphasis
      needs to be on prevention, while in the heavily industrialised countries it needs
      to be focused on prevention of caries, especially root caries.

PMID- 8276520
TI  - The biological approach in oral diagnosis.

PMID- 8276521
TI  - CALOMA: multimedia tutorial programme on oral lesions associated with AIDS/HIV
      infection.

PMID- 8276522
TI  - Evaluation of possible determinants and consequences of Leydig cell heterogeneity
      in man.
AB  - Leydig cells in the human testis are highly heterogeneous, consisting of variably
      staining light and dark cells. The basis for this difference is unknown. The
      present study has assessed whether differing numbers or proportions of dark and
      light Leydig cells are related: (1) to the pronounced inter-individual variation
      in testosterone production by isolated Leydig cells, and (2) to differences in
      structural composition of the testis. Testes (paired weight 6.6-59.48 g) were
      obtained from 27 men aged 72.9 +/- 9.5 years (range 54-89 years) undergoing
      orchidectomy as primary treatment for prostatic cancer. Leydig cells were
      isolated by Percoll-purification and cultured for 20 h under basal and hCG
      stimulated conditions. The proportion of light and dark Leydig cells isolated by
      this method was shown to reflect their proportions in situ, based on the
      morphometric analysis of fixed testicular tissue from the same men. Leydig cells
      isolated from all testes produced testosterone in vitro and responded to
      stimulation by hCG, though the amounts of testosterone produced varied widely
      between subjects. Because of the latter, samples were grouped into 'low' (n = 9),
      'medium' (n = 11) and 'high' (n = 7) groups on the basis of their testosterone
      production. These groups did not differ in their age, testicular size or gross
      testicular morphology, though men in the 'high' group tended to have more total
      Leydig cells per testis. However, there was no overall correlation between
      testosterone production by isolated Leydig cells and the numbers of light or dark
      Leydig cells or their ratio or the total number of Leydig cells per testis. The
      relationship between the volume of light and dark Leydig cells and testicular
      composition was also assessed. The volume of both types of Leydig cells was
      strongly correlated (p < 0.001) with the volume of germ cells, but otherwise
      light and dark Leydig cells correlated positively with different structures.
      Thus, the volume of light Leydig cells correlated (p < 0.001) with the volume of
      blood vessels and of peritubular tissue whereas the volume of dark Leydig cells
      correlated (p < 0.01) with that of the tubular lumen. These differences could
      indicate differences in regulation and/or function of light and dark Leydig
      cells. However, the present data do not support the idea that light and dark
      Leydig cells may differ in their steroidogenic capacity.

PMID- 8276523
TI  - Successful gonadotrophin treatment of hypogonadism in postoperative patients with
      macroprolactinoma and persistent hyperprolactinaemia.
AB  - We report on two males with prolactinoma in whom hyperprolactinaemia and
      hypogonadism persisted for several years postoperatively despite the
      administration of a dopamine agonist or bromocriptine. In these patients, a GnRH
      test revealed no response in the levels of serum LH or FSH. An hCG stimulation
      test provoked no response in the serum levels of testosterone. Case 1, who was 28
      years old at the first visit, received parenteral testosterone and appreciable
      virilization of the genitalia was noted within a few months. When he married and
      desired to father a child, the treatment was switched to hCG/hMG combined therapy
      and spermatozoa appeared subsequently in the ejaculate, although their numbers
      were low. His wife conceived and delivered a healthy baby girl. Case 2 was a
      single young man who presented with hypogonadotrophic hypogonadism and
      hyperprolactinaemia. He was started on hCG injections three times per week and
      the maturation of his genitalia was advanced rapidly. Semen analyses showed sperm
      concentration and motility to be within the normal range. Post-treatment GnRH
      test revealed no improvement in gonadotrophin responses for LH or FSH. In both
      cases, the hCG test repeated after the gonadotrophin treatment showed normal
      basal and stimulated testosterone levels. During the course of gonadotrophin
      treatment in these cases, serum prolactin levels remained elevated, and it is
      suggested that, in the two cases, the hypothalamo-pituitary function was
      disturbed by the tumour or its manipulation and the capacity of the pituitary
      gland to secrete gonadotrophin was impaired. Under such circumstances with
      persisting hyperprolactinaemia, hCG and/or hCG/hMG combination treatment can
      induce normal virilization and advance spermatogenesis sufficiently to achieve
      fertility.

PMID- 8276524
TI  - Prevalence of antisperm antibodies by SpermMARtest in subjects undergoing a
      routine sperm analysis for infertility.
AB  - To evaluate the prevalence of antisperm antibodies (ASA) attached to the sperm
      plasma membrane in male partners of infertile couples, the binding of latex
      particles to spermatozoa was investigated using SpermMARtest, included routinely
      in semen analysis. A total of 860 men were examined, who were referred
      consecutively for semen analysis. Of these, 750 men were referred because of
      infertility (0.6-10 years in duration) whereas 110 were volunteers with a history
      of previous fertility. Samples were assessed by the SpermMARtest kit using latex
      particles sensitized with human IgG. Sperm-latex binding was read after 3 min and
      samples scored as negative, positive or highly positive when < 10, > 10-40, or >
      40% binding occurred, respectively. Of the samples 132 (17.3%) were excluded
      because of azoo- or severe oligo-asthenozoospermia. IgG attached to spermatozoa
      were detected in nearly 13% of semen samples from the infertile population and in
      one of 110 fertile men (0.9%). From the infertile group, 6.2% of samples showed >
      40% binding, and 6.7% intermediate binding, with an overall ASA prevalence of
      12.9% in subjects undergoing semen analysis for infertility.

PMID- 8276525
TI  - Enzymohistochemical and immunohistochemical study of the human efferent ducts.
AB  - An enzymohistochemical and immunohistochemical study of the efferent ducts was
      performed in normal adult men. The epithelium consists of two types of columnar
      cells: principal cells (PCs) and ciliated cells (CCs), and is surrounded by a
      lamina propria (LP) with cells arranged circularly (LPCs). Enzymohistochemical
      study revealed more intense activity of succinic dehydrogenase, NADP, and ATPase
      in the CCs than in the PCs. The LPCs also showed an intense reaction for NADP and
      ATPase. Acid phosphatase activity was only intense in the apical cytoplasm of
      PCs. Immunohistochemical study revealed that antibodies to oestradiol receptor
      related protein (ER-D5) immunostained the PCs and CCs intensely and the LPCs
      weakly. AE1/AE3 antibodies (which stain keratins nos. 1-8 and 14, 15 and 19)
      immunostained the PCs intensely, but was negative in both CCs and LPCs.
      Antibodies to keratin Ks.4.62 (which stain keratin no. 19) immunostained PCs and
      CCs but not LPCs. Epithelial membrane antigen antibodies (EMA) immunostained the
      adluminal surface and apical cytoplasm of PCs. Anti-vimentin antibodies
      immunostained the cytoplasm of PCs and CCs weakly as well as isolated cells in
      the LP. Antibodies to desmin immunostained most LPCs. Antibodies to collagen IV
      immunostained the basal lamina and many extracellular spaces in the LP, mainly
      around the LPCs. The differences between the enzymohistochemical and
      immunohistochemical patterns of the efferent ducts and those of the epididymis
      may help to explain functional differences along the epididymis.

PMID- 8276526
TI  - Sentinels of Leydig cell structural and functional changes in golden hamsters in
      early testicular regression and recrudescence.
AB  - The seasonally breeding hamster model was used to assess changes associated with
      Leydig cell activity and inactivity. Specifically, parameters of Leydig cell
      structure and function were studied to determine the early changes seen in
      seasonally breeding golden hamsters in photoperiod-induced gonadal regression and
      photoperiod-induced gonadal recrudescence. Time intervals used to characterize
      early regression and recrudescence were selected with the objective of
      determining the most sensitive parameters characterizing functional transitional
      states. In early regression, plasma levels of follicle-stimulating hormone (FSH)
      but not luteinizing hormone (LH) or testosterone were reduced significantly.
      Regressive structural changes included decreases in volume of the interstitium,
      total number of Leydig cells, blood vessels, and the seminiferous tubules and
      tubular lumen. A decrease in volume, but not numbers of Leydig cells, was
      accompanied by decreases in volume of Leydig cell tubular smooth endoplasmic
      reticulum (t-ER), Golgi complex, and the peroxisomes and decreases in surface
      area of the inner mitochondrial membrane and t-ER, suggesting that early Leydig
      cell changes are restricted primarily to organelles associated with steroid
      biosynthesis. In early recrudescence, at a time when there was an increase in the
      number of germ cells in the basal compartment, blood levels of LH, FSH and
      testosterone were all increased. There were increases in testicular weight,
      volume, seminiferous tubular lumen, blood vessel and interstitial volumes. Leydig
      cells increased in size as a result of increases in nuclear, nucleolar and
      cytoplasmic volumes, while Leydig cell numbers did not increase. At the
      subcellular level there were increases in the surface areas of the cell,
      mitochondrial membranes and cisternal endoplasmic reticulum (sparsely populated
      with ribosomes). Unlike the changes seen in early degeneration when steroid
      synthetic organelles were initially affected, the changes in early recrudescence
      indicate that Leydig cells must first rebuild their synthetic machinery (nucleus,
      nucleolus and rough endoplasmic reticulum) that, at a later time, will
      reconstitute the cell's steroidogenic machinery. Correlation of hormonal
      parameters with structural parameters did indicate a relationship between
      hormonal parameters and steroid secreting organelles. Correlations were strongest
      with testosterone but, surprisingly, plasma FSH levels correlated more strongly
      with many structural parameters of the Leydig cell than did the levels of LH.
      Since FSH receptors are not present on Leydig cells, these data add to the
      growing data suggesting a role for factors originating from the seminiferous
      tubule in modulation of Leydig cell function.

PMID- 8276527
TI  - Maternal and infant care: comparisons between Western Europe and the United
      States.
AB  - A series of studies between 1986 and 1990 gathered data on maternal and infant
      care in ten Western European countries with lower infant mortality rates than the
      United States and compared the findings both within the European countries and in
      aggregate with the United States. Results from these studies reveal great
      variation among the study countries in how perinatal care is financed, staffed by
      professional and nonprofessional health workers, and provided by public clinics
      or private offices, and in the number of and locale of the recommended number of
      prenatal visits. Invariably consistent among the study countries is the nearly
      complete enrollment of childbearing women in early and continuous prenatal care,
      and the strong linkage of that care to a generous spectrum of social supports and
      financial benefits. None of the benefits generally pertains in the United States.
      The relevance of these observations for the United States suggests that current
      policies intended to lower economic barriers to a highly medicalized version of
      maternity care may yield disappointing results unless the perinatal sequence is
      linked to a more generous set of maternity-related social supports and financial
      benefits than is now contemplated.

PMID- 8276528
TI  - Community-based AIDS services: formalization and depoliticization.
AB  - The 1980s witnessed the development of community-based AIDS service organizations
      across North America. This article looks at how these community groups can become
      increasingly formalized and professionalized over time. The article is based on
      an in-depth examination of one AIDS organization in Ontario, Canada. Interviews
      were conducted with staff members, volunteers, and board members of the
      organization, as well as with knowledgeable individuals in the surrounding
      community. The article identifies ways in which the organization has changed over
      time, and highlights some of the forces which propel these changes. The article
      concludes with a discussion of the political implications of the increased
      formalization of community AIDS groups.

PMID- 8276529
TI  - AIDS in Nicaragua: epidemiological, political, and sociocultural perspectives.
AB  - The AIDS epidemic in Nicaragua is several years behind that in the United States
      and neighboring countries of Central and South America. A combination of events,
      including the isolation caused by the war of the U.S.-backed Contra army against
      the Sandinista government, the complete economic embargo imposed on Nicaragua by
      the United States in 1985, self-sufficiency for blood products, and a low rate of
      recreational injectable-drug use, have contributed to this situation. Since the
      Sandinistas were defeated in the general election of 1990, people have returned
      to Nicaragua from areas where HIV is more prevalent, such as Honduras and the
      United States. It is probable that many HIV-infected persons have now entered the
      country. Because of the high rates of sexually transmitted diseases and cultural
      factors such as "machismo," HIV is likely to spread rapidly by heterosexual
      transmission, unless effective, culturally appropriate education and sexually
      transmitted disease prevention programs are implemented now.

PMID- 8276530
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 article 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 the
      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 article 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- 8276531
TI  - Structural adjustment and health policy in Africa.
AB  - World Bank/International Monetary Fund Structural Adjustment Programs (SAPs) have
      been introduced in over 40 countries of Africa. This article outlines their
      economic policy measures and the experience of the countries that have introduced
      them, in terms of nutrition, health status, and health services. The evidence
      indicates that SAPs have been associated with increasing food insecurity and
      undernutrition, rising ill-health, and decreasing access to health care in the
      two-thirds or more of the population of African countries that already lives
      below poverty levels. SAPs have also affected health policy, with loss of a
      proactive health policy framework, a widening gap between the affected
      communities and policy makers, and the replacement of the underlying principle of
      equity in and social responsibility for health care by a policy in which health
      is marketed commodity and access to health care becomes an individual
      responsibility. The author argues that there is a deep contradiction between SAPs
      and policies aimed at building the health of the population. Those in the health
      sector need to contribute to the development and advocacy of economic policies in
      which growth is based on human resource development, and to the development of a
      civic environment in Africa that can ensure the implementation of such policies.

PMID- 8276532
TI  - The rise and decline of the Cooperative Medical System in rural China.
AB  - The Cooperative Medical System (CMS) in China is an established medical system
      that serves the rural areas and provides treatment and prevention of disease,
      immunization, family planning, and maternal and child health care services. Past
      experience suggests that the CMS benefited the peasants in rural China. During
      the 1980s, following reform of China's economic system, the CMS underwent major
      changes. In some places, CMS stations evolved into various other types of medical
      and health care systems; in other places, CMS stations ceased operation
      altogether. This article attempts to analyze the causes and meaning of these
      changes, and examines the conditions for continuation of this system.

PMID- 8276533
TI  - Health, physical activity level, and employment status in Canada.
AB  - Over the past few years, research from several countries has demonstrated an
      association between unemployment and poor health. In addition, a number of
      studies have established a link between physical activity level and health. As
      yet, however, there has been no comparison of the physical activity levels of the
      employed and the unemployed in a national population and of the extent to which
      the health of the employed and unemployed varies with physical activity levels.
      The research presented in this article demonstrates that in Canada, while the
      unemployed report comparable levels of physical activity to the employed, for all
      levels of physical activity, they are less healthy than the employed, even after
      adjustments are made for age, gender and adequacy of family income. The effects
      of unemployment on health, however, vary by duration of employment. Overall, the
      findings suggest that some benefits of elevated levels of physical activity are
      dampened by the consequences of unemployment.

PMID- 8276534
TI  - An investigation of work and unemployment among psychiatric clients.
AB  - Employment and work can have a positive effect on mental health by providing
      opportunities for skill development, social contact, self-esteem, and income.
      Unemployment is a source of anxiety, stress, and depression. At the same time
      work can be a major source of stress by decreasing opportunities for control and
      autonomy. This article examines the role of work and unemployment and the
      relationship of work status to other indicators of community adjustment among a
      sample of 68 psychiatric clients in outpatient treatment. Comparisons are made
      between clients who are not working or seeking work, those who are unemployed and
      seeking work, and those who are currently working. Regression analysis is then
      used to examine the effect of work status on other indicators of community
      adjustment: psychiatric symptoms, functioning, social integration, stress, and
      mental hospitalizations. Working clients are more likely to be male and younger
      and to have had previous work experience. Working is related to higher levels of
      functioning in the community, while unemployment is positively related to stress.
      Work status was not related to social integration, indicating that work may be an
      alternative source of social support and should receive separate attention in
      assessments of community adjustment and integration.

PMID- 8276535
TI  - Breast cancer: evidence for a relation to fission products in the diet.
AB  - To establish the possible relation between breast cancer mortality and low doses
      of radiation due to fission products in the environment, the mortality rates in
      the nine census regions of the United States for the years 1984-1988 were
      correlated with the cumulative airborne releases from all the nuclear plants in
      each region for the period 1970-1987. A high correlation coefficient of 0.91 was
      obtained for a logarithmic dependence on the total releases, consistent with an
      indirect action via free-radical oxygen at very low dose rates, in contrast to a
      direct action on DNA at high dose rates, explaining the wide differences in risk
      per unit dose obtained in earlier studies. The recent temporal changes of breast
      cancer rates in the New York metropolitan area including nearby Connecticut,
      Westchester, and Long Island were examined in relation to the releases from
      nearby nuclear plants and found to be consistent with a dominant role of short
      lived fission products in drinking water and fresh milk. The results support a
      major role for nuclear plant releases in industrial countries in the recent rises
      of breast and other forms of cancers not related to smoking, especially among
      older persons, and strongly support the need to replace nuclear reactors with
      more benign ways to generate electricity.

PMID- 8276536
TI  - Origin and spread of intra-epithelial carcinoma of the esophagus. Histopathologic
      investigation of the junctions between intraepithelial carcinoma and non
      cancerous epithelium.
AB  - Scrutinization of data on 56 patients of primary esophageal squamous cell
      carcinoma and not given preoperative irradiation therapy disclosed 36 areas
      (64.1%) of intra-epithelial carcinoma contiguous to the main lesion, and in 16
      (28.7%) there was a multiple occurrence of squamous cell carcinoma, in which 13
      were double and 3 were triple carcinomas. A total of 96 junctions between intra
      epithelial carcinoma and non-cancerous epithelium were histologically
      investigated. These junctions could be grouped into two types: well-demarcated
      (29 areas, 30.2%) and ill-demarcated (67 areas, 69.8%) types. The latter was
      separable into 12 (12.5%) of whole layer, 33 (34.4%) of basal layer and 22
      (22.9%) of irregular patterns. Epithelial dysplasia occurred in one (3.4%) of
      well-demarcated and ten (14.9%) of ill-demarcated junctions, and almost all
      lesions of dysplasia were moderate or severe. Thus, most carcinomatous
      transformation had occurred at the site of junction (in-situ carcinogenesis) and
      epithelial dysplasia may be a carcinoma rather than pre-cancerous lesion, per se.

PMID- 8276537
TI  - Oesophageal replacement in adult Nigerians with corrosive oesophageal strictures.
AB  - Literature dealing with the management of undilatable oesophageal strictures in
      Africa is either scanty or non-existent. This report reviews 73 cases of adult
      undilatable corrosive strictures treated by oesophageal replacement at the
      University of Nigeria Teaching Hospital (UNTH) Enugu over a 5-year period (March
      1986 to February 1991). Almost all the cases were suicidal or parasuicidal. All
      the patients had colon transplants; the right colon was used in 68 patients while
      the left colon was used in five patients. The age range was 13 to 48 years with a
      mean of 26 years. There were 65 males and 8 females. Four patients died in the
      postoperative period, earlier on in our surgical experience, a mortality of 5%.
      Of the 69 survivors, 62 patients (90%) experienced no dysphagia after 6-9 months
      of follow-up. Four patients (6%) swallowed with some difficulty while three
      patients who could not swallow at all 6 months after surgery underwent further
      surgery, the strictured upper part of the transplants being replaced with
      myocutaneous tube grafts after which two patients were able to swallow. Major
      postoperative complications were proximal anastomotic leak 49% (34 patients) of
      survivors, wound sepsis 25% (17 patients), tension pneumothorax 7% (five
      patients), colon graft necrosis 4% (three patients), and Ascaris upper intestinal
      obstruction 4% (three patients). The short and medium term results after colon
      transplant for oesophageal corrosive strictures are good. Our experience
      emphasizes the fact that these patients are from the very low social class,
      usually ignorant and most default at the follow-up clinics, once they start
      swallowing.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276538
TI  - Circumferential suture technique for esophageal transection to treat esophageal
      variceal bleeding.
AB  - The EEA stapler has been used routinely for esophageal transection to treat
      esophageal variceal bleeding for some time. It carries the risk of postoperative
      leakage and is not suitable in those cases receiving recent sclerotherapy. The
      circumferential suture technique presented in this paper can be used in any
      situation requiring esophageal transection. It has been utilized by us in twenty
      two emergent cases with good results.

PMID- 8276539
TI  - Epidermal growth factor in gastric carcinoma as a risk factor of postoperative
      recurrence.
AB  - The expression of epidermal growth factor (EGF) was immuno-histochemically
      examined in the primary lesions of 201 patients with advanced gastric cancer who
      underwent curative resection. EGF-positive tumor cells were detected in the
      specimens of 75 patients (37.3%). A significant correlation was observed between
      the extent of lymph node metastasis and EGF expression (p < 0.01), indicating
      that EGF-positive cancer has a tendency to lymph node metastasis. The 2-year and
      5-year survival rates of the patients with EGF-negative tumors were 77.2% and
      63.0%, respectively, while those with EGF-positive tumors were 59.1% and 47.5%
      respectively. The difference in survival rates reached a maximum 2 years after
      surgery, indicating that the patients with EGF-positive gastric cancer had a
      higher risk of early recurrence. Therefore, the amount of EGF produced by a tumor
      may play some role in the growth of metastatic tumors and residual tumor cells
      after surgery, and thus be a potential risk factor in recurrence.

PMID- 8276540
TI  - Colorectal carcinoma in patients aged 75 years and more: factors influencing
      short and long-term operative mortality.
AB  - A review of 238 patients aged over 75 years and operated on for colorectal cancer
      was undertaken to analyse factors influencing short and long-term operative
      mortality. Operative mortality in the first postoperative month was 13% (n = 31)
      and 17% (n = 35) in the first year. Four factors influenced significantly
      postoperative mortality in the first month: postoperative complications (p =
      0.0001) related to medical complications (p = 0.0001), emergency surgery (p =
      0.007), type of anesthesia (p = 0.01). Mortality during the first year (excluding
      patients who died in the first month) was higher in females (p = 0.05), in
      patients subjected to emergency operation (p = 0.004), in patients with
      preexisting, cerebrovascular accident (p = 0.04) and in patients with Dukes C
      staging (p = 0.0001). A multivariate analysis with Cox's model revealed 3
      prognostic factors: Dukes staging (p = 0.0001), medical complications in the
      postoperative period (p = 0.0001) and type of anesthesia (p = 0.0009). Age as an
      isolated factor is not a contraindication to colorectal surgery in elderly
      patients presenting colonic or rectal carcinoma. Prognosis in elderly patients is
      first correlated to the control of postoperative mortality undergoing until the
      first year and then to the cancer itself.

PMID- 8276541
TI  - Hazard and outcome of retreated choledochal cyst patients.
AB  - Thirty-nine patients initially treated for choledochal cyst (25: cyst-enterostomy
      for 15 type I and 10 type IV A, 13: cyst excision for 8 type I and 5 type IV A,
      1: sphincterotomy for type III) have been completely followed up for a mean
      period of 17 years to examine the effect of surgical management on their lives.
      Eighteen of 25 cases with cyst-enterostomy (72%) needed retreatment due to the
      complications but one could not be retreated because of the presence of advanced
      bile duct carcinoma. Fourteen of 17 cases were retreated with cyst excision, of
      whom 12 showed an excellent outcome but other two were suffering from cholangitis
      and hepatolithiasis. The remaining 3 patients retreated with PTCS or cyst
      enterostomy showed a poor outcome. Of 13 patients who had undergone cyst excision
      with hepatico-jejunostomy as the first choice, 12 showed a good outcome but one
      needed retreatment due to the anastomotic stenosis and hepatolithiasis. Thus,
      excision of cyst should be the surgical management for choledochal cyst. However,
      it should be noted that three of 27 patients treated initially or secondarily
      with cyst excision showed unsatisfactory results mainly due to the anastomotic
      stenosis. The results demonstrate that hepaticojejunostomy with a wide opening
      stoma is necessary to prevent postoperative morbidity.

PMID- 8276542
TI  - The mode of lymphatic and local spread of pancreatic carcinomas less than 4.0 cm
      in size.
AB  - To clarify the mode of lymphatic and local spread of small pancreatic carcinomas,
      we studied the histopathology of 33 patients with invasive ductal adenocarcinoma
      of the head of the pancreas less than 4 cm in diameter. Microscopically, lymph
      node metastases were found in 72.7% (24 of 33) of the patients: 17 patients had
      lymph node metastases at the first barrier and 7 patients had lymph node
      metastases at the second barrier. Capsular invasion was present in 21.2% (7 of
      33) patients, retroperitoneal invasion in 84.8% (28 of 33) patients. Invasion to
      the common hepatic artery was identified in 9.1% (3 of 33) patients, and invasion
      to the portal vein system in 24.2% (8 of 33) patients. In addition, five of the
      seven patients with lymph node metastases at the second barrier had spread to the
      periaortic lymph nodes. Thus, even patients with small pancreatic cancers which
      were macroscopically confined to the pancreas showed microscopic extrapancreatic
      tumor extension, especially invasion to the retroperitoneal tissues and to the
      periaortic lymph nodes. This suggests that an aggressive surgical approach,
      including complete resection of surrounding connective tissues in the
      retroperitoneum and extensive lymph node dissection, is necessary to improve the
      surgical therapeutic results even for small pancreatic cancers.

PMID- 8276543
TI  - Results of surgical resection of stage IIIa (N2) non small cell lung cancer,
      according to the site of the mediastinal metastases.
AB  - Out of a series of 1563 consecutive patients submitted to thoracotomy for lung
      cancer between 1980 and 1990, 278 patients underwent a resection for a non small
      cell lung cancer (NSCLC) with mediastinal node metastases (N2). Selection of
      cases for surgery was carried out using CT from 1983 and mediastinoscopy for the
      patients with mediastinal lymph nodes larger than 1.5 cm from 1985: all patients
      with positive mediastinoscopy were excluded from thoracotomy, but 10 cases
      underwent a resection after neoadjuvant radio-chemotherapy. The surgical
      procedures were pneumonectomy (106), lobectomy (146) and atypical resection (8)
      with ipsilateral mediastinal lymphadenectomy. Resection was complete in 236
      patients (84.8%) and incomplete in 42 patients (15.2%). Postoperative mortality
      was 3.2%. Almost all patients received radiotherapy after surgery. Actuarial 5
      year survival was 13.7% for the entire group and 18.5% for the patients who
      underwent curative resection; no patients survived 5 years after palliative
      resection (p < 0.05). There were no differences with regard to prognosis
      according to the histology of the tumors and to surgical procedures. A better
      prognosis is associated with: completeness of resection, involvement of only one
      level, low T classification. Five-year survival rate of patients with metastases
      only in upper mediastinum was 25%; on the contrary 5-year survival rate of
      patients with metastases in the lymph nodes of the lower mediastinum was only 8%
      (p < 0.05). In our opinion better results among the patients with metastases in
      the upper mediastinum depends on the selection obtained with
      mediastinoscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276544
TI  - Clinico-pathologic study of pulmonary metastasis of differentiated thyroid
      carcinoma: age-, sex-, and histology-matched case-control study.
AB  - From 1952 to 1984, 70 primary cases of differentiated thyroid carcinoma with
      pulmonary metastasis were treated. Of these, histopathological sections were
      reviewed in 59 cases (metastasis group). Fifty-nine age-, sex- and histology
      matched cases without pulmonary metastasis were chosen as controls (control
      group). Poorly differentiated features of tumor cells were observed in 57.6% of
      the cases in the metastasis group but in only 27.1% of the control group (P <
      0.001). In contrast, solid and/or trabecular growth patterns were noted in 45.8%
      of the cases in the metastasis group and 52.5% of the control group (P > 0.30).
      No difference in the incidence of vascular or capsular invasion was seen between
      the two groups. These findings suggest that the poorly differentiated features of
      tumor cells rather than the solid and/or trabecular growth pattern or vascular
      invasion of the tumor are more important as histopathologic characteristics of
      differentiated thyroid carcinoma with pulmonary metastasis.

PMID- 8276545
TI  - Prosthetic reconstruction of the chest wall.
AB  - Since January 1987, in a consecutive series of 56 resections of the chest-wall
      for cancer, the wall defect was repaired by a prosthetic implant on 14 occasions
      (10 silastic sheeting, 4 goretex soft tissue patch). Indications for thoracic
      wall resection were: T3 primary lung cancers (7 cases), local recurrences after
      breast cancer surgery (5 cases), primary and metastatic neoplasms arising in the
      chest-wall (2 cases). No rejection was reported nor episodes of flail chest or
      respiratory disorders. No major complications occurred in patients who underwent
      postoperative radiotherapy; only 1 case of persistent seroma was observed.
      Followup ranges from 3 to 37 months. In no case was a local recurrence of tumor
      observed. Cosmetic results were considered from acceptable to good in all
      patients. In every case a total control of pain symptoms was achieved. There were
      6 deaths at a mean interval of 22 months from operation (4 lung cancers, 1 breast
      cancer, 1 osteosarcoma), all due to metastatic spread of the disease.

PMID- 8276546
TI  - A rapid immunoperoxidase method for pathological diagnosis of occult thyroid
      carcinoma.
AB  - The authors report four unusual cases of clinically occult carcinoma of the
      thyroid. Exploratory excision of osseous metastatic lesions was performed for
      diagnosis in Patients 1 and 2, and fine needle aspiration of cervical metastatic
      lesions was used for diagnosis in Patients 3 and 4. A definite diagnosis of
      thyroid cancer could not be made by hematoxylin and eosin staining in Patient 2,
      nor by fine needle aspiration in Patient 3. However, the diagnosis of thyroid
      cancer in both patients was made using the rapid immunoperoxidase method with an
      antibody against thyroglobulin. The rapid immunoperoxidase method reported in
      this paper requires only about 5 minutes. Hence, this rapid staining method may
      be routinely applied to definitive identification of the thyroid as the source of
      metastatic lesions, prior to surgery.

PMID- 8276547
TI  - Penetrating heart wounds.
AB  - In 3 years, 26 patients were operated for penetrating heart wounds at our
      institution, the majority between 30 to 60 minutes after injury. Twenty-two
      patients with a possible heart wound were immediately taken to the operating room
      for thoracotomy. One patient initially underwent laparotomy while 2 were observed
      before operating-room thoracotomy. One patient underwent emergency-room
      thoracotomy. Three patients with no vital signs on admission died, 82.6% of the
      remainder survived. Stab wounds determined the best survival rate: 94%, whereas
      for gunshot wounds it was only 50%. Our experience at this Brazilian Trauma
      Center reveals that delay in reaching the hospital selected the patients, that
      clinical condition on arrival, method of injury (knife or gunshot), emergency
      room staffed with trauma surgeons and aggressive operating room treatment for
      penetrating heart wounds results in a remarkable survival rate. Emergency-room
      thoracotomy should be reserved for patients "in extremis" or when there is no
      operating room available.

PMID- 8276548
TI  - A review of 126 cases of ruptured gravid uterus.
AB  - Ruptured uterus is a grave obstetric complication, associated with high maternal
      mortality and morbidity, perinatal mortality and loss of future fertility as
      hysterectomy is inevitable in many cases. This study reviews the incidence,
      causes and other factors, to define problem areas and propose preventive
      measures. During 1979-1988, 126 cases of ruptured uterus occurred in 46,207
      deliveries; these 126 cases were retrospectively analyzed in relation to causes,
      age, parity, maternal mortality and morbidity, perinatal mortality and
      management. Some of the results were compared with other authors. The incidence
      was 1/367 (2.7/1000 deliveries), traumatic rupture accounted for 42.86% while
      spontaneous rupture accounted for 57.14%. Maternal mortality was 21.43% and the
      perinatal mortality was 73.19%. Supravaginal hysterectomy, repair with
      sterilization and repair without sterilization were the selected lines of
      management. Proper quick diagnosis and prompt management will reduce maternal
      mortality and morbidity. Finally, recommendations to reduce the occurrence of
      this problem are proposed.

PMID- 8276549
TI  - History of surgery of the abdominal cavity. Arabic contributions.
AB  - In-depth historical research is made on Arabic contributions to surgery of the
      abdominal cavity highlighting their specific achievements in laparotomy and
      caesarian section. Albucasis (936-1013) in his book "Al Tasrif" produced the
      first authentic description ever contained in the literature on surgery of the
      abdomen. He described methods of bowel reduction and abdominal wall closure.
      Albucasis used Arabian ant-nippers for intestinal anastomosis; he was the first
      to sew the intestine with fine suture extracted from animal's gut. The manuscript
      of Shahnama or "Book of Kings" written by Ferdowsi (1560-1580) (possessed by the
      Metropolitan Museum of Art in New York), described the earliest caesarian section
      performed on Persian Rustam many centuries B.C. Edinburgh University Library has
      the manuscript entitled "Al-Athar Al-Baqiya An Alqurun Al-Khaliyah" by Al-Biruni
      (1307-1308); it revealed that section had probably been performed on living wives
      of Muslim Kings. Plates No. 65, 73, 81 and 82 illustrating Muslim Surgeons
      performing section were gathered from last two books by Brandenburg in 1982.

PMID- 8276550
TI  - Adrenal cysts: diagnosis and therapeutic approach.
AB  - We report nine cases of adrenal cysts, treated in our hospital, between 1980 and
      1990. The majority of the cases (5/9) were incidental findings on US and CT
      examinations. We operated on 4/9 cases because of their symptomatology or their
      size. Four other cases were managed conservatively; one last case was treated by
      percutaneous drainage under CT. In our series, 1/9 (11%) was a malignant cyst.
      The follow-up shows excellent results in the benign cases and 40 months' survival
      in the malignant case, until today.

PMID- 8276551
TI  - Melanoma in prepubertal children.
AB  - Malignant melanoma in prepubertal children is a rare event. Nine patients, 9.0 +/
      2.4 years (mean +/- S.D.), presented with malignant melanoma between December,
      1975 and August, 1991. The thickness of the lesions ranged from 0.57 to > 4 mm.
      All patients (n = 6) with stage I or II disease are presently alive. Prepubertal
      patients with malignant melanoma tend to exhibit thick lesions when initially
      diagnosed. Their survival appears to be comparable or increased relative to their
      adult counterparts.

PMID- 8276552
TI  - Snuff-box arteriovenous fistulas.
AB  - A total of 192 AV fistulas were created at the anatomical snuff-box. One hundred
      and eighty-two (94.8%) of them were patent and ready for use at the end of one
      month. This fistula has several advantages over the more commonly performed
      Brescia-Cimino radio cephalic fistula at the distal forearm. Snuff-box fistula is
      easier to perform, has a better patency rate, fewer wound complications and
      preserves proximal sites for fistula.

PMID- 8276553
TI  - Candida prosthetic valve endocarditis. An autopsy review.
AB  - Fungal endocarditis after cardiac surgery has been noticed increasingly in the
      past decade. We report a case of Candida parapsilosis endocarditis after mitral
      valve replacement in a patient with no predisposing factors. In this report we
      mainly examined the pathological findings in this patient with post-mortem
      examination.

PMID- 8276554
TI  - A comparison of pulmonary functions and oxygenation following local, spinal or
      general anaesthesia in patients undergoing inguinal hernia repair.
AB  - In order to compare the pulmonary effects of various anaesthetic techniques, 49
      otherwise healthy patients needing inguinal hernia repair were randomized to
      general, spinal or local anaesthesia. Blood gases were drawn and spirometry
      performed pre- and postoperatively at fixed intervals. Results showed a superior
      ventilation and oxygenation pattern for local anaesthesia (p < 0.05). No
      statistically significant differences were found between the groups with respect
      to forced vital capacity (FVC) or forced expiratory volume per second (FEV1) but
      patients who had spinal anaesthesia performed worse, and for the group as a whole
      there was a significant reduction compared to preoperative values. We conclude
      that local anaesthesia is less detrimental to pulmonary function in inguinal
      hernia operations than spinal or general anaesthesia.

PMID- 8276555
TI  - Hemodynamic advantages of temperature sensing rate adaptive pacemaker.
AB  - During activity, the increase in body temperature triggers the pacemaker to
      adjust by increasing the rate. To assess the hemodynamic advantages twelve
      patients were studied. Heart function was measured by a noninvasive bioimpedance
      method. Heart functions were measured first at rest and then at the end of the
      exercise. Exercise was done in temperature mode and then later at a fixed heart
      rate. Cardiac output increased by 64% in temp mode compared to the fixed heart
      rate during the exercise. Stroke Volume increased by 38%. The Thoracic Fluid
      Index, Ventricular Ejection Time, Ejection Velocity Index and Ejection Fraction
      were unchanged. Hemodynamics are better in temp sensing rate responsive pacing
      during activity compared to fixed rate pacing. Clinically, the patients are doing
      well.

PMID- 8276556
TI  - Predictive value of ASA classification for the assessment of the perioperative
      risk.
AB  - To assess the predictive value of the ASA classification for morbidity and
      mortality during the whole time of post-operative hospitalization, data of 2248
      patients undergoing elective surgery were analyzed prospectively. The incidence
      of post-operative morbidity, considering surgical as well as non-surgical
      complications, rose from 3.9% in ASA class I to 33.7% in ASA class IV. No patient
      died in ASA I, whereas 7.2% died in ASA IV. Furthermore, the ASA classes
      corresponded with the postoperative outcome of the patients, taking into account
      both the length of stay at the ICU and the postoperative hospitalization. The
      duration at the ICU increased an average of 0.1 to nearly 4 days and
      hospitalization from 11.8 to 27.3 in ASA classes I and IV, respectively. The
      results were confirmed considering separated groups with a different operative
      stress and risk. ASA-classification is also of conceivable value in estimating
      the perioperative risk and should therefore be considered prior to surgical
      intervention.

PMID- 8276557
TI  - Enoxaparin in the prevention of deep venous thrombosis after major surgery:
      multicentric study. The Italian Study Group.
AB  - DVT is a very frequent complication of general surgery. Heparin and, more
      recently, LMWHs can successfully prevent post surgical thromboembolism. One
      thousand one hundred and twenty-two patients (533 males and 589 females; mean age
      62.2 +/- 11.4 yrs) were enrolled in a multicentre controlled study, to evaluate
      the efficacy and safety of enoxaparin in comparison to calcium heparin in the
      prevention of deep venous thrombosis (DVT) following general surgery. Patients
      assigned to the enoxaparin and the calcium heparin groups received 1 daily dose
      of 20 mg (2000 I.U.) and 2 daily doses of 0.2 ml (5000 I.U.), respectively
      starting 2 hours before the operation. Both drugs were given by subcutaneous
      route. A Doppler or Duplex Scan diagnosis of DVT was made in 3 (0.5%) patients in
      the enoxaparin group (2 cases during treatment and 1 patient at the end of
      treatment) and in 6 (1.1%) patients in the calcium heparin group (5 cases during
      treatment and 1, bilateral, after the end of treatment). Pulmonary embolism (PE)
      was ascertained by angiography in 1 patient (0.18%) in the enoxaparin group and
      in 2 patients (0.36%) in the calcium heparin one. Hemorrhagic complications
      occurred in 29 patients (5.2%) in the enoxaparin group and in 34 (6.1%) in the
      calcium heparin group. Haematomas located in the injection site were reported in
      16.1% and 25.3% in the enoxaparin and calcium heparin groups respectively (p =
      0.0001). Local pain in the injection site at the 5th day of treatment was
      reported in 8.4% and 16.6% in the enoxaparin and calcium heparin groups
      respectively (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276558
TI  - Symptomatic leiomyoma of the adrenal.
AB  - Small leiomyomas of the adrenal gland are pathologic curiosities, usually
      discovered incidentally at autopsy, and thought to arise from smooth muscle of
      the adrenal vasculature. We report the clinical, radiologic and pathologic
      features of a symptomatic adrenal leiomyoma, which, to our knowledge, represents
      the first recorded example.

PMID- 8276559
TI  - Drug resistance of coagulase-negative staphylococci from patients with urinary
      tract infection.
AB  - The drug resistance of 202 coagulase-negative staphylococci (CNS) strains
      isolated from patients with urinary tract infection (UTI) at urinary colony
      counts of 10(5) or more between 1989 and 1991 was studied. Of the 202 strains,
      185 were submitted from UTI patients with underlying urinary disorders
      (complicated UTI patients) and became rapidly resistant to the majority of drugs
      tested. In addition, the incidence of methicillin-resistant or multiple drug
      resistant CNS tended to increase. These resistant strains were significantly more
      frequently isolated in patients with fever, which was strongly suspected to be
      due to CNS UTI. These results suggest that the prevalence of drug resistance in
      CNS from the urinary tract rapidly increases and drug-resistant CNS aggravate CNS
      UTI.

PMID- 8276560
TI  - Urinary glycosaminoglycan excretion following extracorporeal shock wave
      lithotripsy.
AB  - A clinical study was designed to investigate whether extracorporeal shock waves
      altered the urinary excretion of glycosaminoglycans and if they have a diagnostic
      value in determining the extent of the renal tissue damage. A total of 25
      consecutive patients were treated for renal stone by extracorporeal shock wave
      lithotripsy (ESWL) with Siemens Lithostar and were studied 24 hours before, then
      24 hours and 30 days after ESWL. Urinary excretion of glycosaminoglycans was
      significantly increased after 24 hours but the difference from the pre-ESWL
      period was insignificant 30 days later. These results showed that extracorporeal
      shock waves induce an acute increase in the excretion of glycosaminoglycans, but
      this elevation is transient and probably reflects negligible ultrastructural
      damage to the glycosaminoglycan-containing renal and extrarenal structures.

PMID- 8276561
TI  - Non-Hodgkin lymphoma mimicking primary retroperitoneal tumour on computed
      tomography.
AB  - We report a case of non-Hodgkin lymphoma with CT showing a single, bulky, and
      round retroperitoneal mass mimicking primary retroperitoneal tumours or
      metastatic lymph node. On MRI, the tumour was presumed originating from lymph
      nodes but we could not judge whether the tumour was due to lymphoma or
      metastasis.

PMID- 8276562
TI  - Metastasis of Grawitz's tumour in the ureteral stump.
AB  - Metastasis of a tumour in the ureteral stump after nephrectomy for a primary
      tumour is very rare. Only 44 cases have been published so far. Our paper reports
      on a metastasis of Grawitz's tumour in the ureteral stump diagnosed 28 years
      after nephrectomy for a primary tumour. The authors have shown a low biological
      activity in this tumour.

PMID- 8276563
TI  - Carcinoma of the colon after ureterosigmoidostomy and trigonosigmoidostomy for
      exstrophy of the bladder.
AB  - Two cases of adenocarcinoma of the colon developing 28 and 33 years after
      ureterosigmoidostomy and trigonosigmoidostomy are described. The mechanisms of
      neoplastic transformation and the clinical implications are discussed.

PMID- 8276564
TI  - A case of transitional cell carcinoma of the bladder presenting with brain
      metastases.
AB  - A patient with brain metastases from transitional cell carcinoma of the bladder
      is presented. This patient had multiple intracranial metastases. The disease
      progressed very aggressively despite systemic chemotherapy and he died in a very
      short time. In a review of the literature it is noticed that the incidence of
      brain metastases from transitional cell carcinoma of the bladder has increased
      recently. This is probably because of the current complicated therapeutic
      approach to bladder carcinoma, including radical surgery and combination
      chemotherapy for high stage disease.

PMID- 8276565
TI  - Methotrexate, vinblastine, adriamycin and cisplatin (MVAC) chemotherapy for the
      treatment of advanced bladder carcinoma.
AB  - Thirteen patients with advanced urothelial transitional cell carcinoma were
      treated with methotrexate, vinblastine, adriamycin and cisplatin combination. No
      complete remissions were achieved in patients with disseminated diseases; only
      three out of five patients (60%) with localized tumours in the bladder or
      perivesical space responded completely. Localized tumour recurrences in the
      bladder occurred in two of three complete responders at the ninth and tenth
      months after chemotherapy. Four patients died during or after chemotherapy: one
      from disease progression and the remainder from chemotherapy complications.
      Authors conclude that, although 23% complete and 30.8% partial remissions were
      achieved with the MVAC chemotherapy, strict toxicity monitoring and careful
      selection of patients are essential because of its non-negligible complications.

PMID- 8276566
TI  - Small cell carcinoma of the prostate. A case report.
AB  - A case of small cell carcinoma of the prostate reported here was studied by
      immunohistochemical and electron microscopic procedures. Most tumour cells were
      positive for argyrophil (Grimelius) stain and had dense core neurosecretory
      granules in the cytoplasm. But immunohistochemical staining revealed vasoactive
      intestinal polypeptide and calcitonin only in a few cells, and it was still
      obscure what kinds of hormones were produced in this tumour. By dot blot
      hybridization, our case showed no amplification of myc family gene which is
      suggested to be associated with a poor clinical outcome in pulmonary small cell
      carcinoma.

PMID- 8276567
TI  - Leydig cell tumour of the testis: presentation of two cases.
AB  - Two cases of Leydig cell tumour of the testis with no hormonal and metastatic
      manifestations are presented. Clinical features of the disease are discussed.

PMID- 8276568
TI  - Management of urethral stricture in patients practising clean intermittent
      catheterization.
AB  - Clean intermittent catheterization (CIC) is used commonly to treat patients with
      impaired bladder emptying. We treated 6 male patients who were experiencing
      difficulty with intermittent catheterization. Retrograde urethrography
      demonstrated stricture of the urethra in all of them and a false passage as well
      in one patient. Treatment consisted of urethral dilatation using filiform and
      followers in 4 patients and optical internal urethrotomy in the remaining 2
      patients followed by urethral stenting using a 16 Fr. Teflon Foley catheter in
      all. The stenting Foley catheter was removed after 2 weeks. Subsequently 5 of the
      6 patients had resumed CIC regimen to empty their urinary bladder. The sixth
      patient with a false passage could not perform CIC and suprapubic cystostomy was
      performed. During a follow-up of 6 of 18 months, none of these five patients
      developed recurrence of urethral stricture and all are practising CIC without any
      difficulty. Analysis of our data revealed that forceful manipulation during
      catheter insertion and significant urethral bleeding during catheterization are
      important contributory factors for the development of urethral stricture in
      patients practising CIC.

PMID- 8276569
TI  - Plasma catecholamine concentration and dopamine-beta-hydroxylase activity during
      haemodialysis with acetate or bicarbonate at different sodium concentrations in
      hypotensive patients.
AB  - Plasma catecholamines (noradrenaline, adrenaline, dopamine) and dopamine-beta
      hydroxylase were investigated in hypotensive haemodialysis patients treated with
      different sodium dialysate concentrations in acetate or bicarbonate fluids. The
      present results suggest that most physiological reactions could be obtained in
      patients treated with equimolar sodium concentration in blood and dialysis fluids
      in both kinds of acetate and bicarbonate.

PMID- 8276570
TI  - Contrast-to-noise-ratio measurements in three-dimensional magnetic resonance
      angiography.
AB  - RATIONALE AND OBJECTIVES: The authors report on the development and preliminary
      validation of a technique for measuring contrast-to-noise ratio (CNR) at all
      points along selected vessel segments in the original three-dimensional magnetic
      resonance angiography (MRA) dataset. METHODS: Contrast-to-noise ratio
      dependencies on flow rate, field of view, and flip angle were measured on images
      from a conventional time-of-flight MRA pulse sequence using constant flow in a
      branching vascular phantom. An estimate of the inherent variability of the
      technique was obtained from multiple scans of a flow phantom and a human
      volunteer. RESULTS: The overall standard deviation (SD) of the CNR was found to
      be approximately 6.1% of the average CNR value for the flow phantom study and
      7.3% for the human study. Vessel CNR was found to increase with field of view and
      was found to become nonuniform for low flow rate and/or high flip angles.
      CONCLUSION: In general, such CNR measurements allow the investigation of the
      mechanism of signal loss and general technique optimization in MRA.

PMID- 8276571
TI  - Magnetic resonance imaging of hereditary spontaneous hepatitis in Long-Evans
      cinnamon rats.
AB  - RATIONALE AND OBJECTIVES: Long-Evans Cinnamon (LEC) rats have abnormal metal
      metabolism and spontaneously develop hereditary hepatitis. The influence of in
      vivo metals on magnetic resonance imaging (MRI) was studied using LEC rats.
      METHODS: Short spin-echo images of the livers of LEC rats were obtained using a
      7.05-T small-bore MR unit. Effectively, these images were proton-density images
      because of T2-shortening mechanism in high magnetic field. The LEC rats were
      imaged during pre-, acute, and chronic hepatitis phases. The accumulation of
      copper and iron in the livers of LEC rats was evaluated. RESULTS: Signal
      intensities, which were homogeneous throughout the liver in every phase,
      decreased in the acute hepatitis phase and recovered in the chronic hepatitis
      phase. Copper was accumulated in all phases. Iron was observed grossly in the
      hepatocytes in the acute phase, but decreased in the chronic phase. CONCLUSIONS:
      Signal intensities of proton-density images of the livers of LEC rats in phases
      of pre-, acute, and chronic hepatitis were influenced by iron.

PMID- 8276572
TI  - Stability studies on chemoembolization mixtures. Dialysis studies of doxorubicin
      and lipiodol with Avitene, Gelfoam, and Angiostat.
AB  - RATIONALE AND OBJECTIVES: Chemoembolization, using a combination of embolic and
      chemotherapeutic agents, appears to be an effective treatment for hepatocellular
      carcinoma. Although the postulated mechanism of effectiveness hinges on a
      prolonged drug delivery, increasing evidence suggests that embolization mixtures
      are not stable. The objective of this study was to investigate examples of these
      mixtures. METHODS: Dialysis techniques have been used to examine the
      pharmacokinetic properties of chemoembolization mixtures that contain
      doxorubicin, Lipiodol (Guerbet Products, Montreal, Quebec), and the embolizing
      agents Avitene (Alcon Laboratories Inc., Fort Worth, Texas), Gelfoam (Upjohn,
      Kalamazoo, MI), and Angiostat (Regional Therapeutic Inc., Pacific Palisades, CA).
      RESULTS: Lipiodol, Gelfoam, and Avitene, when combined with doxorubicin, had only
      a small effect on the diffusion of the drug when compared with the diffusion
      curve of doxorubicin alone. Gelfoam or Avitene produced a thrombus-like
      consistency when added to a doxorubicin/Lipiodol combination, and an additional
      decrease in the doxorubicin appearance rate was observed. However, after 6 hours,
      doxorubicin levels for these mixtures reached control values observed in 3 hours.
      Angiostat without Lipiodol produced a profound concentration-dependent decrease
      in the diffusion of doxorubicin. After 9 hours, only 23% of the doxorubicin had
      been released. CONCLUSION: The strong complexing ability of the embolic agent
      Angiostat may enable it to be a carrier for doxorubicin and surpass other
      mixtures currently employed for transcatheter chemoembolization.

PMID- 8276573
TI  - Characterization of iopromide liposomes.
AB  - RATIONALE AND OBJECTIVES: Iopromide-carrying liposomes were prepared and were
      characterized pharmaceutically and biologically. METHODS: The liposomes were
      prepared by the ethanol evaporation method and were characterized by quasi
      elastic light scattering (size) and equilibrium dialysis (encapsulation
      efficiency and stability). Acute and subchronic toxicity was tested in mice
      and/or rats and cardiovascular tolerance in rabbits. Pharmacokinetic parameters
      were determined in rats. Computed tomography (CT) imaging efficiency was obtained
      from rat and rabbit studies. RESULTS: The mean diameter was 0.5 +/- 0.1 micron
      and the encapsulation efficiency ranged between 30% and 40%. The liposomes were
      stable in human and rabbit plasma for approximately 24 hours. The LD50 in mouse
      and rat was approximately 3 g iodine/kg. In a subchronic toxicity study in rats
      with six doses of 1 g iodine/kg given every three days, no adverse effects were
      observed. The pharmacokinetics in rats were dose-dependent. Increasing the dose
      resulted in lower total clearance, and longer terminal half-life. Elimination of
      iodine was complete and the main route of excretion was via the kidneys. A
      clinically relevant computed tomography enhancement of the liver was reached
      after approximately 200 mg iodine/kg in rats and 150 mg iodine/kg in rabbits.
      CONCLUSIONS: The iopromide-carrying liposomes were well tolerated in animal
      studies and seemed to be suitable for the imaging of the liver.

PMID- 8276574
TI  - Red-cell trapping in the rat renal microcirculation induced by low-osmolar
      contrast media and mannitol.
AB  - RATIONALE AND OBJECTIVES: In acute renal failure after ischemia, intravascular
      obstruction by trapped red blood cells in the microvasculature of the renal outer
      medulla is a consistent finding. The influence of intravenously injected contrast
      media (CM) on such obstruction was investigated. METHODS: Anesthetized rats were
      subjected to 45 minutes of unilateral renal ischemia. Red-cell trapping in
      ischemically injured kidneys and in the contralateral uninjured kidneys was
      estimated from the intrarenal distribution of 51Cr-labelled erythrocytes after
      injection of ioxaglate or iopamidol in a dose of 1,600 mg I/kg body weight. As an
      osmolar control substance, mannitol (950 mOsm/kg) was given to a third group and
      isotonic Ringer's solution was administered to a fourth group. RESULTS: In the
      uninjured kidneys, treatment with ioxaglate or mannitol resulted in no red-cell
      trapping, while the iopamidol-treated group showed red-cell trapping in the inner
      stripe of the outer medulla in a dose-dependent manner. In the ischemically
      injured kidneys, both CM and mannitol enhanced the red-cell trapping in the inner
      stripe of the renal medulla. CONCLUSION: The results indicate that intravenously
      administered ioxaglate and iopamidol enhance the microvascular obstructions
      evoked by ischemic injury and that iopamidol may induce local impairment in renal
      medullary microcirculation in a normal kidney.

PMID- 8276575
TI  - Dynamic contrast bolus computed tomography for the assessment of renal function.
AB  - RATIONALE AND OBJECTIVES: We preliminarily investigated whether dynamic contrast
      bolus computed tomography (CT) could be used to measure glomerular filtration
      rate. METHOD: After bolus intravenous contrast injection, rapid sequence CT scans
      were performed at a fixed level through the kidneys and aorta in three patients
      with biochemically normal renal function who underwent routine CT examination. A
      mathematical technique developed initially for positron-emission tomography was
      adapted for analysis of the CT data for measurement of renal contrast clearance
      per unit renal volume and of the fraction of renal tissue occupied by blood
      volume. RESULTS: Renal blood volumes in the 3 patients were 0.28, 0.29, and 0.31
      of total renal volume, respectively, and the corresponding contrast clearances
      were 0.44, 0.41, and 0.35 mL per min per mL of renal tissue. CONCLUSIONS: This
      preliminary study in normal patients demonstrates that dynamic contrast CT might
      be developed for clinical physiological renal studies. Further work to validate
      the accuracy and reliability of the method in comparison with established isotope
      methods is suggested.

PMID- 8276576
TI  - Radiologists' responses to patients' inquiries about imaging results. A pilot
      study on opinions of various groups.
AB  - RATIONALE AND OBJECTIVES: The authors analyzed opinions regarding how a
      radiologist should answer a patient's or patient's family's questions about
      radiologic results. METHODS: Questionnaires were obtained in a university
      hospital from 135 physicians of various specialties, including radiologists, and
      501 nonphysicians, such as medical students, nurses, patients, families of
      patients, and hospital personnel. The questionnaire included three questions,
      each with five choices. The first question concerned a normal result, the second
      a minor abnormality, and the third a major abnormality. The five choices in each
      question consisted of two suggestive answers to patients' inquiries and three
      excuses for the refusal of immediate answers. Respondents were asked to choose
      the single most desirable and the single least desirable answer. RESULTS:
      Approximately 50% of all physicians believed that a radiologist should refer the
      patient to his or her physician rather than to give a suggestive answer to a
      patient with an abnormality. Considerably fewer physicians had a similar opinion
      in cases involving a patient with normal results. Patients and the families of
      patients believed that a radiologist should give at least a suggestive answer in
      any circumstances where the patient is agitated to know the result. Radiologists
      were reluctant to convey any information regardless of the test result.
      CONCLUSIONS: Physicians had significantly different opinions from patients and
      the families of patients, and radiologists preferred to keep their traditional
      role of referral physician.

PMID- 8276578
TI  - Educational efficacy of computer-assisted instruction with interactive videodisc
      in radiology.
AB  - RATIONALE AND OBJECTIVES: To create a robust, functional computer-assisted
      instruction (CAI)-videodisc program and to demonstrate its educational efficacy.
      METHODS: After creating a CAI-videodisc program in skeletal radiology for a two
      screen Macintosh system, 36 medical students and 162 radiology residents entered
      a controlled study with paired pre- and posttests. Subjects also compared CAI
      videodisc with other educational media. RESULTS: Medical students using the CAI
      videodisc improved their mean pre- and posttests. Subjects also compared CAI
      videodisc with other educational media. RESULTS: Medical students using the CAI
      videodisc improved their mean pre- and posttest scores from 50.9 to 70.9 (P <
      .001, control group scores 50.1 and 50.6) and residents (using a different test)
      improved from 45.4 to 70.9 (P < .001, control group scores 49.6 and 46.1).
      Medical students and residents favored CAI-videodisc over teaching files,
      textbooks, videotapes, and slide-audiotapes. CONCLUSIONS: A functional CAI
      videodisc program was created and demonstrated to be educationally effective.

PMID- 8276577
TI  - Radiologists' responses to patients' inquiries about results.

PMID- 8276579
TI  - The role of imaging in the diagnosis of carpal tunnel syndrome.
AB  - Potentially, imaging of the carpal tunnel may expand our understanding of the
      pathogenesis of CTS. Future studies should correlate imaging results with the
      patients' clinical status and results of electrodiagnostic tests. Canal pressure
      studies are not clinically routine, but a research study correlating canal
      pressure with canal appearance might be of interest. The diagnostic accuracy of
      imaging studies needs further clinical validation. Currently, it is premature to
      promote or advertise carpal tunnel imaging as a diagnostic modality for CTS.

PMID- 8276580
TI  - Total quality management in cardiovascular and interventional radiology.

PMID- 8276582
TI  - Clinical practice versus research: how can radiology win?

PMID- 8276581
TI  - Large paratesticular mass in an 18-year-old man.

PMID- 8276583
TI  - Computer-aided diagnosis in chest radiography. Preliminary experience.
AB  - RATIONALE AND OBJECTIVES: Computer-aided diagnosis (CAD) schemes for chest
      radiography are being developed with which to alert radiologists to possible
      lesions, and thus potentially improve diagnostic accuracy. However, CAD schemes
      have not been tested on a large number of clinical cases. The authors identify
      design parameters that would be required for development of an intelligent
      workstation. METHODS: Computer-aided diagnosis programs were applied for the
      automated detection of lung nodules, cardiomegaly, and interstitial infiltrates
      to 310 consecutive chest radiographs, and were analyzed for potential usefulness
      and limitations. Computer-aided diagnosis output was evaluated by radiologists
      and physicists for accuracy and technical problems, respectively. RESULTS:
      Approximately 70% of the results were judged to be potentially acceptable;
      however, the number of false-positive findings was relatively high. Technical
      problems included failure to detect subtle abnormalities and the occurrence of
      false-positive detections caused by normal anatomical structures. CONCLUSION:
      Computer-aided diagnosis has the potential to be a valuable aid to radiologists
      in clinical practice, if certain technical problems can be overcome and if
      optimal operating points can be defined for clinical use.

PMID- 8276584
TI  - Correlation of sequential magnetic resonance imaging of experimental brain
      ischemia with histologic changes in gerbils.
AB  - RATIONAL AND OBJECTIVES: To characterize Gd-DTPA-enhanced T1-weighted images (Gd
      T1WI) in the acute phase of cerebral ischemia, sequential magnetic resonance
      images of 84 Mongolian gerbils with occlusion of the left common carotid artery
      were evaluated. METHODS: Twelve gerbils were used for each group, among which the
      occlusion time (5-180 minutes, permanent) varied. Histopathologic changes
      developing within the first 2 weeks were compared with patterns on T2-weighted
      images and Gd-T1WI on a 7.05-Tesla system. RESULTS: Although T2-weighted images
      and Gd-T1WI both demonstrated abnormal findings as early as 3 hours after
      occlusion, Gd-T1WI demonstrated more definite abnormalities with shorter
      occlusion than T2-weighted images (especially when there were only mild
      histologic changes). The earliest changes were an abnormal enhancement around and
      within the lateral ventricles in temporary occlusions; this was not demonstrated
      in permanent occlusions. CONCLUSIONS: Magnetic resonance images using Gd-DTPA
      demonstrated abnormal permeability within 3 hours after occlusion, and the
      pattern is correlated with intensity of ischemia.

PMID- 8276585
TI  - [Alopecia psoriatica. Characteristics of an up to now neglected disease picture].

PMID- 8276586
TI  - [Retinoids in therapy of granuloma anulare disseminatum].
AB  - We report on four patients with granuloma annulare disseminatum successfully
      treated with etretinate as basic medication. In two cases there was complete
      remission after treatment with initial doses of up to 0.9 mg/kg body weight
      etretinate. One patient did not respond to etretinate alone but the condition was
      cured when Re-PUVA therapy was administered in addition. In another patient, with
      widespread granuloma annulare, primary treatment with Re-PUVA was instigated,
      followed by low-dose monotherapy with etretinate. According to these findings, we
      propose a three-stage regimen of therapy. After checking that the indications are
      appropriate, we first initiate monotherapy with etretinate and switch to a low
      dose treatment over a longer period on response. If there is no response we
      switch to the second stage, i.e. Re-PUVA therapy; the third is then etretinate
      monotherapy to prevent relapse.

PMID- 8276587
TI  - [Benzalkonium chloride--a relevant contact allergen or irritant? Results of a
      multicenter study of the German Contact Allergy Group].
AB  - At eight dermatological clinics, a total of 2146 patients were tested between May
      1990 and December 1991 to determine the significance of the preservative
      benzalkonium chloride in inducing allergic contact dermatitis and to evaluate
      recommendations for patch testing. In 225 cases an allergic reaction was proven,
      with 258 irritant reactions in addition. Only 12 cases were clinically relevant.
      Therefore, benzalkonium chloride is considered a weak allergen. A doubtful
      (erythema) or an incipient positive (with occasional papules) reaction may be
      regarded as an irritant reaction. In isolated cases a "repeated open application
      test" (ROAT) should be applied to determine clinical relevance. Our
      recommendation for patch testing is 0.1% benzalkonium chloride in vaseline, and
      also in water for special cases.

PMID- 8276588
TI  - [Fine needle aspiration cytology of metastatic malignant melanoma. Improvement of
      results with ultrasound control].
AB  - A review of 315 fine-needle aspiration cytologies (FNAC) carried out from 1984
      through 1992 in 157 patients with suspected metastatic melanoma was carried out:
      176 results were confirmed by histological examination and 139 by clinical follow
      up. In the first period, from 1984 through 1988, we observed 5 false-negative
      results out of 123 evaluable FNACs. All were caused by technical failure. In the
      second period, from 1988 through 1992, all fine-needle biopsies of impalpable
      masses were done with ultrasound guidance. Thus, we were able to avoid further
      false-negative results. No errors in interpretation were found. We obtained 219
      true-positive and 91 true-negative results with 97.8% sensitivity, 100%
      specificity, 98.4% accuracy, 100% positive and 94.8% negative predictive value.
      In 3 cases with metastatic melanoma the cytological diagnosis only was 'malignant
      tumor', while in another 5 patients the cytodiagnosis of melanoma was not
      definitive. Immunocytology was helpful in these cases in identifying melanoma.
      FNAC allowed the correct diagnosis of a second malignancy in 4 cases (one
      papillary thyroid cancer, one Hodgkin's disease, two non-Hodgkin's lymphomas). No
      complications occurred. In our opinion, FNAC--for poorly defined lesions with
      ultrasound guidance--is a very rapid, safe and accurate method that allows
      reliable diagnosis of metastatic melanoma.

PMID- 8276589
TI  - [Photochemotherapy (PUVA) of acute graft-versus-host disease].
AB  - For several years, psoralen and UV-A light (PUVA) therapy has been used in the
      treatment of chronic graft-versus-host disease (GvHD) following allogeneic bone
      marrow transplantation (BMT). There is little experience with PUVA treatment of
      acute GvHD. Allogeneic BMT was performed in 25 patients, 10 of whom developed
      acute GvHD despite immunosuppressive therapy. Six patients with acute cutaneous
      GvHD grade II-III (n = 2 grade II, n = 4 grade III) were treated with PUVA. We
      present the results. All the PUVA-treated patients improved markedly after 5-12
      sessions of irradiation. In 5 patients the skin cleared completely with 8-18
      treatments. In 4 patients chronic GvHD was prevented by maintenance treatment for
      up to 10 months. Following clearing of acute cutaneous GvHD, 2 patients developed
      chronic GvHD after therapy-free intervals of 3 and 12 months, respectively. These
      results indicate a beneficial effect of PUVA in acute cutaneous GvHD and suggest
      a protective effect against chronic GvHD.

PMID- 8276591
TI  - [UV-A-1 therapy of subacute cutaneous lupus erythematosus].
AB  - Because of relative contraindications to corticosteroid or immunosuppressive
      treatment, a 71-year-old female patient with subacute cutaneous lupus
      erythematosus underwent serial whole-body irradiation with extremely long-wave
      ultraviolet light (UVA-1). The cumulative dosage was 186.1 J/cm2 within 9 weeks.
      Impressive improvement was achieved with some delay.

PMID- 8276590
TI  - [Vascular function parameters in idiopathic and quartz-induced progressive
      scleroderma].
AB  - In 15 patients with systemic sclerosis (SS) and 8 patients suffering from
      silicosis and/or silica dust exposure-associated scleroderma (SAS), various
      parameters of endothelial cell and platelet function and of blood coagulation and
      fibrinolysis were studied. In 9 of the 23 patients the values for the von
      Willebrand factor antigen were increased, and the same applied to the endothelin
      levels in 8 of 23 patients. Protein C, protein S, anti-thrombin III and tissue
      plasminogen activator (before and after 10 min venous occlusion) were normal. The
      plasminogen activator inhibitor, however, was increased in 5 patients. Increased
      levels of platelet factor 4 and of beta-thromboglobulin were found in 20
      patients, while the ADP- and epinephrine-induced platelet aggregation was reduced
      in 5 patients. No individual patient was found to have a general disturbance of
      all parameters. The deviations in the parameters of endothelial cell and platelet
      function and of blood coagulation and fibrinolysis proved to be rather
      inconsistent. This suggests different functional stages in dependence on the
      various influential factors. There was no close correlation either with the
      severity of Raynaud's phenomenon or with the type of SS. In addition, there were
      no basic differences between SS and SAS. The disturbances occurred with similar
      frequency and in similar proportions in both disease groups.

PMID- 8276592
TI  - [Incontinentia pigmenti in a male infant].
AB  - Bloch-Sulzberger incontinentia pigmenti (IP) is a rare X-linked neuroectodermal
      syndrome. Over 97% of the patients are female. We report on a male baby who
      developed blisters in linear groups or bands shortly after birth. When the child
      was 3 months old the blisters were followed by verrucous papules, which cleared
      after 1 year leaving areas of brownish grey hyperpigmentation. In addition to the
      skin involvement, our patient showed central motor dysfunction on the right side
      of the body and also dental and ocular anomalies. Both parents were in good
      health. Chromosome analysis yielded a normal karyotype (46, XY). The genes for
      coagulation factor VIII and biglycan in the Xq28 region were not deleted. The
      presence of the disease in this male infant may be due to an early somatic
      mutation or a half-chromatid mutation. A further possibility is mosaic expression
      of an unstable premutation. This model offers a good explanation for the reports
      in the literature of transmission of the disease from mother to son.

PMID- 8276593
TI  - [Multiple familial glomangioma].
AB  - Multiple familial glomangiomas are rare vascular tumours, which are inherited as
      an autosomal dominant trait. They usually arise at puberty or later, and may
      involve all parts of the skin. In contrast to solitary glomangiomas, they are not
      painful. Histopathologically, they are characterized by widely dilated vascular
      spaces, surrounded by only a few glomus cells. In a report on two patients, the
      clinical, histopathological and immunocytochemical features and the differential
      diagnosis of multiple familial glomangiomas are discussed.

PMID- 8276594
TI  - [Hibernoma of the forehead. A rare tumor of brown fatty tissue in an unusual
      site].
AB  - We report a hibernoma located on the forehead in a 52-year-old female patient.
      The hibernoma is a rare tumour derived from brown adipose tissue. Location on the
      forehead is unusual and has not been reported before.

PMID- 8276595
TI  - [Pseudo-ainhum in Vohwinkel disease. Keratoma hereditarium mutilans].
AB  - An 11-year-old Turkish boy who has suffered from palmoplantar keratosis since his
      first year of life is presented. He is the only one of a large family to be
      affected. The diffuse keratosis extends to the back of the hands and feet and
      still has a progressive course. At the age of 6 he developed a symmetric high
      tone acoustic impairment and at 10, an ainhum-like constricting band around the
      fifth digit of the left hand. This constellation of symptoms is highly
      characteristic for mutilating keratoma (Vohwinkel's disease), which is a rare
      disorder of keratinization. The majority of cases in the literature have had an
      autosomal dominant pattern of inheritance, although sporadic cases like this have
      also been reported as well. If constricting band proceeds to the point where
      spontaneous amputation seems imminent, a therapy with orally administered
      retinoids should be considered.

PMID- 8276596
TI  - [Is the use of oil in epiluminescence microscopy necessary?].

PMID- 8276597
TI  - [Do infections with Mycoplasma hominis and Ureaplasma urealyticum no longer count
      as sexually transmissible diseases?].

PMID- 8276598
TI  - [Transmission of HIV by leeches?].

PMID- 8276599
TI  - [What can be done in unexpected extension of skin tumors to the periorbital
      region?].

PMID- 8276600
TI  - [Memorial meeting for M. Kaposi in the "Moriz Kaposi Komitat Hospital" Kaposvar,
      Hungary].

PMID- 8276601
TI  - [Dermatologic roentgen therapy. Current status].

PMID- 8276602
TI  - Between a rock and a hard place.

PMID- 8276603
TI  - Behaviour disturbance: routine assessment of children at three years.
AB  - Behavioural problems in pre-school children can be a major source of parenting
      and family anxiety. Early identification through routine screening can prevent
      problems escalating, writes Paul Stallard. It can also offer an opportunity to
      reassure anxious parents. Here he describes a behaviour checklist used by health
      visitors in Bath district to identify and help parent deal with behaviour
      problems in their young child.

PMID- 8276604
TI  - Asthma campaign aims to cut deaths.

PMID- 8276605
TI  - Language disorder--James: a case history.
AB  - When James was born he seemed the perfect baby. But gradually Venetia Young
      became concerned about his slow development. Despite repeated reassurance from
      health professionals, including her health visitor, she persisted in seeking
      medical opinion and finally learned that James had a language disorder. Here she
      describes his early years, the warning signs of his language problem and her
      battle against the experts' disbelief.

PMID- 8276606
TI  - Unusual behaviours associated with autism.
AB  - Autism occurs in an estimated 115,300 people in the UK and can be diagnosed in
      children as young as eighteen months. The diagnosis is based upon the presence of
      unusual behaviour that makes the child appear quite different from ordinary
      children. National autism week takes place next month, to raise awareness of the
      condition. Here, Tony Attwood describes typical behaviours associated with
      autism.

PMID- 8276607
TI  - Constipation: a family-centred approach.
AB  - Constipation in childhood is a common problem, causing great concern to parents.
      Palo Almond describes the problem, its management and the medical, social and
      psychological issues involved. Greater health visitor input could result in fewer
      referrals to the consultant paediatrician for treatment, she suggests.

PMID- 8276608
TI  - Breath-holding: helping parents cope.
AB  - Breath-holding is relatively rare but can occur in infants as young as six
      months. Ann Rowland describes some typical episodes and suggests strategies to
      help parents cope.

PMID- 8276609
TI  - Failure to thrive--tackling feeding problems: a community-based approach.
AB  - Failure to thrive rings fewer alarm bells these days in comparison with other
      concerns such as child sexual abuse. Yet, writes Diana Hampton, it remains a
      significant source of anxiety to parents and professionals working in child
      health and development. Here she describes a Children's Society project which
      aims to tackle the problem of failure to thrive through one-to-one work with
      families in their own homes.

PMID- 8276610
TI  - 'My baby doesn't need me': understanding bonding failure.
AB  - Little is known about the prevalence of failure to bond, what causes it and its
      consequences for both mother and baby. A number of different factors may be
      implicated, such as caesarean birth, a crying baby or lack of support from the
      mother's partner, and it undoubtedly has an effect on the mother-child
      relationship. Andy Sluckin describes and analyses the experiences of six women in
      the context of recent studies into bonding failure and puts the case for
      specialist therapy, without which, he suggests, improving the relationship
      between mother and child may be slow and only partially successful.

PMID- 8276611
TI  - Bonding failure: a case study.

PMID- 8276612
TI  - Promoting the health promoting school.
AB  - The Health of the Nation strategy commits the government to establishing a
      national network of health-promoting schools. Alysoun Moon describes an
      independent pilot project in Wandsworth, south London which is pioneering the
      concept in ten selected primary schools.

PMID- 8276613
TI  - Safe as houses.

PMID- 8276614
TI  - Students: desperately seeking sponsorship.
AB  - NHS employers have cut back radically on the number of health visitors whose
      training they are prepared to support. 'Your rights at work' examines the
      difficulties facing nurses embarking on health visitor training and warns of
      common pitfalls hidden in student contracts. Health visitor students need to be
      in membership of an appropriate trade union such as the HVA, with specialised
      experience in dealing with their particular needs and concerns.

PMID- 8276615
TI  - Wonderland world.

PMID- 8276616
TI  - Health for all women.

PMID- 8276617
TI  - Simply the best.

PMID- 8276619
TI  - Health visitors fight job cuts.

PMID- 8276618
TI  - Teenagers. Years of living dangerously.

PMID- 8276620
TI  - Getting the right angle.

PMID- 8276621
TI  - Standards. Safety in numbers.

PMID- 8276622
TI  - Racism. Not just an East End problem.

PMID- 8276623
TI  - Community care. Working together for better health.
AB  - The purpose of community care is to promote privacy, dignity and independence and
      provide resources for living. It is a philosophy not a place, writes Stephen
      Watkins. In this extract from the Medical Practitioners' Union evidence to the
      house of commons health committee enquiry on community care, he sets out a new
      blueprint for the organisation and funding of a seamless health and social
      service based on joint, locality-based commissioning and practice-based case
      management.

PMID- 8276624
TI  - HIV/AIDS. Caring for families in the community.
AB  - Primary health care workers have a vital role in offering advice, support and
      comfort to families affected by Aids and HIV, write Sue Appleby and Corinne
      Moore. Here they describe the specialist health visiting service provided in
      Parkside, west London, for parents and children with HIV infection. But generic
      health visitors and school nurses must also be aware of the issues and alert to
      signs of undiagnosed infection as they are likely to be increasingly involved in
      providing a 'normal' service to families affected by Aids/HIV.

PMID- 8276625
TI  - HIV/AIDS health promotion: a way forward.
AB  - Health promotion on HIV/Aids should be integral to the work of health visitors
      and school nurses, writes Michael Watson. But this work must be fully evaluated
      to ensure effectiveness. Here he describes the evaluation of HIV/Aids health
      promotion and looks in particular at approaches and methods suitable for
      individual professionals and districts.

PMID- 8276626
TI  - Mothers' awareness of HIV and AIDS.
AB  - Health visitors in Northamptonshire carried out a survey of mothers attending
      child health clinics to determine their knowledge and awareness of HIV and Aids.
      The aim was to ascertain levels of need for further health education for
      professional health workers and, in turn, their client groups. Susan J Stevens et
      al describe the results of the survey which revealed widespread lack of knowledge
      among women of childbearing age.

PMID- 8276627
TI  - HIV and quality of life: a rehabilitation perspective.
AB  - Access to families affected by HIV in their own home puts health visitors in a
      prime position to encourage health promotion strategies for people with HIV
      infection, and to recognise and make early referral for rehabilitation needs,
      writes Cherry Lang. Here she describes how physiotherapy and stress management
      techniques can help tackle symptoms of HIV infection.

PMID- 8276628
TI  - Thalassaemia: 2 of 3. Current community knowledge.
AB  - In this second of three articles Simon Dyson, Verna Davis and Rafeya Rahman
      describe a study carried out in Manchester for the sickle-cell anaemia and
      thalassaemia centre to gauge the extent of community awareness about
      thalassaemia, the likely level of demand for further information and how that
      information might most usefully be given.

PMID- 8276629
TI  - Teamwork. Blazing a trail through valium valley.

PMID- 8276630
TI  - Compensation for work-related injuries.

PMID- 8276631
TI  - Retiring in style.
AB  - The NHS pension scheme is widely regarded by pensions experts as one of the best.
      It offers a more generous deal than other, private sector schemes for the
      equivalent contributions. However it is not yet open to nurses employed in
      general practice and there are a number of issues of which health visitors and
      school nurses working in the NHS should be aware.

PMID- 8276632
TI  - Cow growth hormone ban.

PMID- 8276633
TI  - (CT)n and (GT)n microsatellites: a new class of genetic markers for Salmo trutta
      L. (brown trout).
AB  - Thirteen (GT)n and four (CT)n microsatellite loci (n = 10 or more and n = 20 or
      more, respectively) have been isolated from a partial genomic library of brown
      trout and sequenced. On average, a (GT)n repeat sequence occurs approximately
      every 23 kb and a (CT)n repeat sequence every 76 kb in brown trout genome.
      Primers for DNA amplifications using the polymerase chain reaction (PCR) were
      synthesized for three single locus microsatellites. Mendelian inheritance of the
      observed polymorphisms was confirmed in full-sib families. Four brown trout
      populations (10 unrelated individuals per population) were screened for
      polymorphism with these three microsatellite loci. The total number of alleles
      detected in the four populations is five at one locus, six at the other two
      microsatellite loci and is three, on average, per population. Heterozygosities
      range from 0.18 to 0.74. The largest differences in allelic frequencies occurred
      between the Mediterranean and the Atlantic populations: this result is congruent
      with previous allozymic data. The gene-centromere distances of the three
      microsatellite markers were determined on gynogenetic lines: post-reduction rates
      range from 0.17 to 0.60. For all the three microsatellite loci, the primers
      designed from brown trout sequences can be used in another closely related
      species of salmonid, the rainbow trout (Oncorhynchus mykiss). This last aspect
      supports the view that microsatellite markers may have wide application in
      genetic studies in salmonid species and fishes in general.

PMID- 8276634
TI  - Allozyme variability in the Italian wolf (Canis lupus) population.
AB  - Multilocus protein electrophoresis was used to estimate genetic variability in a
      sample of 38 Italian wolves (Canis lupus). Percentage of polymorphic loci was p =
      10.0 per cent (four polymorphic loci out of 40 examined), and average observed
      heterozygosity was Ho = 0.028. Genotypes were in Hardy-Weinberg equilibrium.
      Electrophoretic analysis does not indicate a significant reduction of genetic
      variability at nuclear gene loci following at least one century of isolation from
      other European populations and demographic fluctuations suggested by recent range
      contraction and expansion. These findings are compared with published allozyme
      and mitochondrial DNA data for dogs, Canadian wolves, and introgressed wolf x
      coyote populations from Minnesota and Isle Royale (U.S.A.).

PMID- 8276635
TI  - Further studies of a staggered hybrid zone in Mus musculus domesticus (the house
      mouse).
AB  - In the extreme north-east of Scotland (near the village of John o'Groats) there
      is a small karyotypic race of house mouse (2n = 32), characterized by four
      metacentric chromosomes 4.10, 9.12, 6.13 and 11.14. We present new data on the
      hybrid zone between this form and the standard race (2n = 40) and show an
      association between race and habitat. In a transect south of John o'Groats we
      demonstrate that the clines for arm combinations 4.10 and 9.12 are staggered
      relative to the clines for 6.13 and 11.14, confirming previous data collected
      along an east-west transect (Searle, 1991). There are populations within the John
      o'Groats-standard hybrid zone dominated by individuals with 36 chromosomes
      (homozygous for 4.10 and 9.12), which may represent a novel karyotypic form that
      has arisen within the zone. Alternatively the type with 36 chromosomes may have
      been the progenitor of the John o'Groats race. Additional cytogenetic interest is
      provided by the occurrence of a homogeneous staining region on one or both copies
      of chromosome 1 in some mice from the zone.

PMID- 8276636
TI  - Fertility estimates in the Tunisian all-acrocentric and Robertsonian populations
      of the house mouse and their chromosomal hybrids.
AB  - The reproductive features of wild all-acrocentric and 2n = 22 Robertsonian (Rb)
      house mice (M. m. domesticus) from Tunisia were studied. The aim was to examine
      the possibility of a reproductive selective advantage associated with chromosomal
      change as well as to measure the effect of heterozygosity for a large number of
      Rb fusions on the fertility of hybrids. Results showed that litter sizes were
      significantly smaller in Rb than in all-acrocentric mice. This difference, which
      may represent a favourable demographic strategy related to the habitat
      segregation observed in the Tunisian mice, needs to be studied further. The F1
      hybrids between the two chromosomal races showed a significantly reduced
      reproductive success and litter size (respectively, 53 per cent and 60 per cent
      less than either parental race). Analysis of the testicular histology of F1 and
      backcross males showed in some cases a breakdown of spermatogenesis. The degree
      of this disturbance was not related to the level of chromosomal heterozygosity
      suggesting that genetic incompatibilities between the two genomes might be
      involved. The strong reduction in fertility measured in these hybrids represents
      a reproductive isolating mechanism effectively reducing gene flow between the all
      acrocentric and 22Rb mice populations of Tunisia.

PMID- 8276637
TI  - Autosomal suppressors of sex-ratio in Drosophila mediopunctata.
AB  - The sex-ratio trait has been described as the production of progenies with excess
      of females due to X-linked meiotic drive in the parental males. This trait has a
      variable expression in Drosophila mediopunctata. We describe here the existence
      and chromosomal localization of autosomal suppressors of sex-ratio in this
      species. There are at least four such genes (one on each major autosome) and the
      strongest effect is localized on chromosome IV. These genes possibly result from
      the operation of 'Fisher's Principle'; a mechanism of Natural Selection leading
      to a 1:1 sex ratio.

PMID- 8276638
TI  - Histochemical demonstration of copper in LEC rat liver.
AB  - Livers of LEC rats were histochemically stained for copper according to the
      modified Timm's method, which includes trichloroacetic acid (TCA) treatment. TCA
      pretreatment was effective in removing zinc and iron, leaving as the major metal
      in the liver. Hepatocytes in 3-month-old rats were stained intensely by the
      modified Timm's method, both in frozen sections and in paraffin-embedded
      specimens. The centrilobular hepatocytes were usually stained, but positive cells
      were also randomly distributed in the hepatic lobes, showing a mosaic pattern.
      The staining was intensified in 8- compared to 3-month-old LEC rats. In contrast
      hepatocytes from LEA rats, the normal counterpart of LEC rats, were faintly
      stained for copper. Proliferating cholangioles found in older LEC rats were shown
      to lack copper deposition, and hepatocellular carcinoma showed less copper
      deposits than the hepatocytes surrounding the tumor. The copper staining was
      augmented in livers of LEC rats subjected to copper-loading, but was less intense
      in the livers treated with D-penicillamine. The staining intensity under the
      various experimental conditions showed good correlation with the copper
      concentration. Lysosomal deposition of copper in hepatocytes was demonstrated by
      electron microscopic analysis for copper. Thus the modified Timm's method was
      shown to produce valuable results in demonstrating copper in LEC rat livers,
      providing important information for an understanding of the mechanism of copper
      deposition and hepatic disease of the animal.

PMID- 8276639
TI  - Sarafotoxin expression in the bronchopulmonary tract: immunohistochemical
      occurrence and colocalization with endothelins.
AB  - The immunohistochemical occurrence of sarafotoxin (SRTX), a snake venom peptide
      under strong evolutionary control, was investigated in the pulmonary diffuse
      neuroendocrine system (PDNES) of newborn cats and rats. By applying the avidin
      biotin-peroxidase complex method on serial lung sections, we have demonstrated
      its distribution and colocalization with different endothelin (ET) isoforms. A
      light microscopic study revealed apparent immunostaining for SRTX in neuronal
      components and smooth muscle tissue and in neuroepithelial bodies (NEB), while
      isolated neuroendocrine cells (NEC) remain unlabelled. Comparison of the SRTX
      reactivity pattern with that of different ET peptides on adjacent lung sections
      showed colocalization of SRTX-b with ET-3 in NEB, intrapulmonary ganglion cells
      and nerve fibres, on the one hand, and with ET-1 in airway and vascular smooth
      muscle cells, on the other. These findings, in addition to the remarkable
      functional and structural similarities between SRTX and ET peptides, suggest a
      common evolutionary origin and biological significance of sarafotoxin and
      endothelins. Moreover, this is the first time that a toxic peptide has been
      demonstrated in the PDNES.

PMID- 8276640
TI  - Glycogen phosphorylase activity and immunoreactivity during pre- and postnatal
      development of rat brain.
AB  - Catalytic activity and immunoreactivity of glycogen phosphorylase were studied in
      pre- and postnatal rat brain. The catalytic activity was assayed in brain
      homogenates; immunoreactivity was investigated by immunoblot analysis using a
      monoclonal anti-bovine brain glycogen phosphorylase antibody. The cellular
      localization and intensity of immunoreactivity were analysed on paraffin-embedded
      sections utilizing the same monoclonal antibody. The catalytic activity increased
      10-fold from embryonic day 16 to adult; immunoreactivity became detectable on
      embryonic day 16 and increased in intensity as the enzyme activity rose to adult
      values. The first cellular elements to be stained immunohistochemically were
      ependymal cells lining the ventricles, ependymal cells of the choroid plexus,
      meningeal cells and a selected population of neurons in the brain stem. The
      immunoreactivity of plexus cells and meningeal cells was reduced or absent in the
      adult rat brain. The earliest appearance of glycogen phosphorylase
      immunoreactivity in astroglial cells was seen at postnatal day 9 in the
      hippocampus. The staining pattern of the adult brain was reached at day 22 post
      partum. The developmental changes in glycogen deposition and in glycogen
      phophorylase activity and immunoreactivity may indicate a variable physiological
      role of glycogen metabolism for different cell types in the pre- and postnatal
      periods.

PMID- 8276641
TI  - Fibres of intermediate type 1C and 2C are found continuously in mdx soleus muscle
      up to 52 weeks.
AB  - The mdx mutant is a murine homologous model of Duchenne muscular dystrophy (DMD).
      Fibre types determined by the myosin-ATPase technique in soleus muscles were
      compared in C57BL/10 control and mdx mice from 3 to 52 weeks of age. The control
      strain continuously presented 70% of type 2 fibres whereas the mdx strain showed
      an increase to 80% at 6 weeks and a subsequent decline. In mdx muscles, necrosis
      which begins at 3 weeks of age did not affect specifically one type of fibre.
      Type grouping was never observed when muscle regeneration occurred. Fibres of
      intermediate type (1C and 2C) were found continuously up to 52 weeks of age in
      the mdx mutant. The foci of small immature regenerating fibres were of type 2C
      but never 1C. A few mature fibres were either of type 2C or 1C. We suggest that
      the presence of intermediate type fibres could result from the co-expression of
      type 1 and 2 myosin heavy chains, indicating a transition from type 2 to type 1
      in regenerating fibres.

PMID- 8276642
TI  - In situ hybridization of atrial natriuretic peptide mRNA in the endothelial cells
      of human umbilical vessels.
AB  - The localization of mRNA encoding preproatrial natriuretic peptide (ANP) was
      investigated in cultured human umbilical vein endothelial cells (HUVEC) and
      tissue preparations of umbilical vein and artery. The techniques used were in
      situ hybridization and in situ hybridization combined with immunocytochemistry,
      using 32P-radiolabelled and non-radioactive digoxigenin labelled complementary
      RNA probes. Human ANP mRNAs are mainly localized in the endothelial cells of the
      umbilical vein and, to a lesser extent, in the endothelial cells of the umbilical
      artery. The autoradiographic labelling and the intensity of digoxigenin staining
      were significantly reduced by treatment with RNase before in situ hybridization.
      This study provides unequivocal evidence for the expression of the ANP gene in
      the endothelial cells of human umbilical vessels, confirming that these
      endothelial cells have the ability to synthesize this peptide. The functional
      significance of the presence of the ANP mRNA in the endothelial cells of human
      umbilical vessels is discussed.

PMID- 8276643
TI  - Taurine-like immunoreactivity in octopaminergic neurones of the cockroach,
      Periplaneta americana (L.).
AB  - Taurine (2-aminoethanesulphonic acid) is reported to interact with the
      octopaminergic system. The distribution of taurine-like immunoreactivity (-LIR)
      in relation to octopamine-like immunoreactive dorsal unpaired median (DUM)
      neurones was investigated with the aim of revealing possible colocalization of
      these two neuromediators. The specificity of the anti-taurine serum used was
      demonstrated by dot blot immunoassay and by use of preabsorption controls. There
      was no crossreactivity with octopamine. The specificity of the octopamine
      antiserum employed has been described elsewhere. Taurine-LIR could be
      demonstrated in large dorso-median cells in the suboesophageal and the
      mesothoracic ganglion as well as in the abdominal ganglia. In addition taurine
      LIR is distributed in numerous other regions of the ganglia. A comparison of the
      immunostaining for taurine and octopamine indicates that several of the taurine
      like immunoreactive (-LI) neurones are probably members of the octopamine
      immunoreactive DUM cell population. These taurine-LI neurones resemble octopamine
      LI DUM cells in soma position and size as well as in the projections of their
      primary neurites. Colocalization of octopamine-LIR and taurine-LIR within the
      same neuronal element could be shown by alternate immunostaining of consecutive
      sections. It is probable that all octopamine-LI DUM neurones also exhibit taurine
      LIR, and the possible physiological significance of this coexistence is
      discussed.

PMID- 8276644
TI  - Quantitative aspects of enzyme histochemistry on sections of freeze-substituted
      glycol methacrylate-embedded rat liver.
AB  - Freeze-substituted rat liver embedded in glycol methacrylate (GMA) has been used
      to demonstrate the activities of several enzymes. The following enzymes could be
      detected in GMA-sections by the indicated histochemical procedure(s): 5'
      nucleotidase (lead salt, cerium-diaminobenzidine), alkaline phosphatase (indoxyl
      tetrazolium salt), catalase (diaminobenzidine), acid phosphatase (diazonium
      salt), lactate dehydrogenase (tetrazolium salt) and glutamate dehydrogenase
      (tetrazolium salt). The activities of all these enzymes were dramatically
      decreased compared with the activities demonstrated in unfixed cryostat sections,
      with the exception of catalase. The activities of the following enzymes could not
      be detected in GMA-sections: glucose-6-phosphate dehydrogenase (tetrazolium
      salt), xanthine oxidoreductase (tetrazolium salt), D-amino acid oxidase (cerium
      diaminobenzidine-cobalt-hydrogen peroxide) and glucose-6-phosphatase (cerium
      diaminobenzidine). The possible role of restricted penetration of reagents into
      the resin was studied by measuring cytophotometrically the enzyme activities in
      GMA-sections of 3 and 6 microns in thickness. For all the enzymes that could be
      detected, the 6 microns:3 microns ratio varied from 1.4 to 2.7. An eventual
      retarded penetration of reagents into the resin was investigated by measuring
      cytophotometrically the amount of final reaction product during incubation for
      acid phosphatase and glutamate dehydrogenase activities. In both cases linear
      relationships without a lag phase were found for the specific enzyme activities
      with incubation time. Chemical denaturation of proteins or masking of active
      sites in proteins due to embedding in the resin monomer may be considered to be
      the main cause of decreased enzyme activities.

PMID- 8276645
TI  - Immunocytochemical demonstration of erythropoietin in hypoxic human hepatoma
      cultures.
AB  - The possibility of demonstrating erythropoietin at the light microscopic level
      was examined in homogenous cultures of the erythropoietin-producing human
      hepatoma cell lines HepG2 and Hep3B. Immunoperoxidase staining was applied in
      combination with several mono- and polyclonal antibodies. Sufficiently strong
      colour responses were obtained with all three polyclonal antibodies and with one
      of three monoclonal antibodies raised against recombinant human erythropoietin.
      The staining intensity was increased in hypoxic versus nonhypoxic hepatoma
      cultures. Intracellular erythropoietin immunoreactivity was confirmed by Western
      blot analysis of HepG2 extracts. The effect of oxygen supply on erythropoietin
      gene expression was confirmed by competitive polymerase chain reaction of
      erythropoietin mRNA and by radioimmunoassay of secreted erythropoietin.

PMID- 8276646
TI  - Localization of NADPH-diaphorase activity in the dental pulp, periodontium and
      alveolar bone of the rat.
AB  - In this study we examined the presence and localization of nicotinamide adenine
      dinucleotide phosphate diaphorase (NADPH-d) activity in the dental pulp,
      periodontal tissues and alveolar bone of the rat. The presence of NADPH-d
      activity was also examined in cat pulp. The rat histochemical analysis revealed
      the presence of prominent NADPH-d activity both in cells of the sub-odontoblastic
      cell layer and in the odontoblasts, in the root as well as in the coronal pulp
      regions. In the pulpal horns, odontoblasts often had long processes with a high
      level of labelling indicating NADPH-d activity extending through the predentin
      and dentin. Moreover, endothelial cells of pulpal blood vessels were positive for
      NADPH-d in both species. However, no clearcut examples were found of pulpal nerve
      fibres positive for NADPH-d in the rat or cat and denervation performed in rats
      did not alter the enzyme staining patterns. In the periodontal tissue, NADPH-d
      activity was localized to cells on the alveolar bone surface of the periodontal
      ligament and, in addition, alveolar bone marrow crypts were filled with intensely
      labelled cells. In the gingival papillae, NADPH-d activity was observed in the
      basal cell layer of the epithelium. Endothelial cells of periodontal and gingival
      blood vessels showing positive staining for NADPH-d were occasionally noted.

PMID- 8276647
TI  - Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of
      the uterine cervix: a clinical trial.
AB  - PURPOSE: This study is a prospective randomized clinical trial undertaken at our
      center to compare low dose rate versus high dose rate intracavitary brachytherapy
      for the treatment of carcinoma uterine cervix. METHODS AND MATERIALS: From June
      1986 to June 1989, 482 patients with previously untreated invasive squamous cell
      carcinoma of the uterine cervix were entered into the study. After an initial
      clinical examination and investigative work-up the patients were staged according
      to FIGO staging system. Depending upon the stage of the disease, the size of the
      local growth and the local cervical anatomy, the patients were divided into two
      main groups. In group I patients, the predominant treatment was by intracavitary
      therapy and in group II patients, the predominant therapy was by external beam
      radiation. In both the groups at the time of intracavity brachytherapy the
      patients were alternately randomized to receive either low dose rate or high dose
      rate brachytherapy. There were thus two hundred forty-six patients in the low
      dose rate group and two hundred thirty-six patients in the high dose rate group.
      The patients were analyzed for local control, 5 years survival and late radiation
      morbidity. RESULTS: Stage for stage the local control rates in the low dose rate
      group and high dose rate group were similar. The overall local control achieved
      in the low dose rate group was 79.7% as compared to 75.8% in the high dose rate
      group. The 5 years survival figures in the low dose rate and high dose rate group
      were also comparable. In Stage I, it was 73% for low dose rate patients and 78%
      for high dose rate patients, for Stage II it was 62% and 64% respectively and for
      Stage III patients it was 50% and 43%. The only statistically significant
      difference was found in the incidence of overall rectal complications which was
      19.9% for the low dose rate group as compared to only 6.4% for the high dose rate
      group. However, the more severe grade 3-4 complications were not significantly
      different between the two groups (2.4% vs. 0.4%, respectively). The bladder
      morbidity in both the groups was similar. CONCLUSION: Thus high dose rate
      intracavitary brachytherapy is an equally good alternative to conventional low
      dose rate brachytherapy in the treatment of carcinoma of the uterine cervix.

PMID- 8276648
TI  - Total-body irradiation and cataract incidence: a randomized comparison of two
      instantaneous dose rates.
AB  - PURPOSE: To assess the influence of instantaneous total-body irradiation dose
      rate in hematological malignancies, we randomized 157 patients according to
      different instantaneous dose rates. METHODS AND MATERIALS: Between December 10,
      1986 and December 31, 1989 157 patients have undergone a total-body irradiation
      before bone-marrow transplantation according to two different techniques: either
      in one fraction (1000 cGy given to the midplane at the level of L4, and 800 cGy
      to the lungs) or in six fractions (1200 cGy over 3 consecutive days to the
      midplane at the level of L4, and 900 cGy to the lungs). Patients were randomized
      according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6
      vs. 15 cGy/min) and fractionated (3 vs. 6 cGy/min) TBI groups; there were 77
      cases for the LOW and 80 for the HIGH groups, with 57 patients receiving single
      dose (28 LOW, 29 HIGH) and 100 patients receiving fractionated total-body
      irradiation (49 LOW, 51 HIGH). RESULTS: As of July 1992, 16 (10%) of 157 patients
      developed cataracts after 17 to 46 months, with an estimated incidence of 23% at
      5 years. Four (5%) of 77 patients in the LOW group, 12 (15%) of 80 patients in
      the HIGH group developed cataracts, with 5-year estimated incidences of 12% and
      34%, respectively (p = 0.03). Ten (18%) of 57 patients in the single-dose group,
      and 6 (6%) of 100 patients in the fractionated group developed cataracts, with 5
      year estimated incidences of 39% and 13%, respectively (p = 0.02). When the
      subgroups were considered, in the single-dose group, 3 (11%) of 28 LOW patients,
      and 7 (24%) of 29 HIGH patients developed cataracts, with 5-year estimated
      incidences of 24% and 53%, respectively; in the fractionated group, 1 (2%) of 49
      LOW patients, and 5 (10%) of 51 HIGH patients developed cataracts, with 5-year
      estimated incidences of 4% and 22%, respectively (single-dose LOW vs. single-dose
      HIGH vs. fractionated LOW vs. fractionated HIGH, p = 0.006). There was no
      statistically significant difference in terms of 5-year estimated cataract
      incidence between the patients receiving steroids and those not (30% vs. 25%, p =
      0.22). Multivariate analyses revealed that the instantaneous dose rate was the
      only independent factor influencing the cataractogenesis (p = 0.04). CONCLUSION:
      We conclude that the total-body irradiation regimen (instantaneous dose rate
      and/or fractionation) may have an influence on the development of cataracts
      following bone-marrow transplantation.

PMID- 8276649
TI  - Increased chronic bowel complications with split-course pelvic irradiation.
AB  - PURPOSE: To assess the possible impact of various treatment factors including
      split-course versus continuous course treatment on the incidence of chronic bowel
      complications in patients receiving adjuvant pelvic radiotherapy. METHODS AND
      MATERIALS: A retrospective review was performed of records of 153 patients
      treated with adjuvant external beam pelvic radiation therapy without
      brachytherapy for endometrial and colorectal carcinomas. Continuous course
      radiotherapy was administered in 91 patients (59%) and 62 patients (41%) received
      split course treatment with a planned 2 week mid-treatment break. Mean pelvic
      dose and daily fraction size were 51.4 and 1.71 Gray, respectively. Multiple
      patient and treatment variables were assessed for their possible relationship to
      chronic bowel complications. Univariate and multivariate statistical analyses
      were carried out. RESULTS: Twenty-seven patients (18%) developed chronic bowel
      complications at a median interval of 12 months after radiotherapy. Of all
      factors analyzed, only the use of split course technique was associated with a
      significantly higher rate of chronic bowel injury and decreased complication-free
      survival (p = 0.009). CONCLUSION: This study supports earlier suggestions that
      the use of split course rather than continuous course pelvic radiotherapy can
      increase late intestinal complication rates. Possible pathophysiologic mechanisms
      are discussed.

PMID- 8276650
TI  - Patterns of failure following loco-regional radiotherapy in the treatment of
      limited stage small cell lung cancer.
AB  - PURPOSE: The probability of treatment resistant cells developing in a tumor, such
      as small cell lung cancer (SCLC) which has a rapid cell cycle time, is a function
      of the number of tumor cells present and of time. Theoretically, the development
      of resistance to chemotherapy and radiotherapy should be minimized by using all
      treatment modalities early in the treatment program. METHODS AND MATERIALS: The
      importance of the timing of loco-regional radiotherapy was assessed in a multi
      institution randomized study. Three hundred and eight patients with limited small
      cell lung cancer (LSCLC) were given three cycles of cyclophosphamide, doxorubicin
      and vincristine alternating with three cycles of etoposide and cisplatin. In
      addition, patients were randomized to receive locoregional radiotherapy: 40 Gy in
      15 fractions in 3 weeks with treatment planning techniques to limit the spinal
      cord dose to be < or = 35 Gy either with the first cycle (early) or with the
      sixth cycle of chemotherapy (late). Responding patients received prophylactic
      brain irradiation (25 Gy in 10 fractions in 2 weeks) after completion of
      locoregional radiotherapy and chemotherapy. RESULTS: 96% of the 155 eligible
      patients allocated to the "early" arm and 87% of the 153 allocated to the "late"
      arm received locoregional radiotherapy; 26 patients did not receive locoregional
      radiotherapy. The mean field sizes were similar in both arms. The mean radiation
      doses were significantly less in the "early" arm (p = 0.0319 Wilcoxon rank sum
      test). Any differences in the frequency of toxicities were minor. All patients
      have been followed for at least 2 years and the median follow up is 4 years. 64%
      had a complete response in the "early" arm compared with 56% in the "late" arm (p
      = 0.137). Survival was measured from the start of chemotherapy. There was a
      significant improvement in survival in the "early" arm; median survival was 21.2
      months compared with 16.0 months in the "late" arm (p = .008 log rank test).
      Survival at 2, 3, and 4 years was 40%, 32%, and 25%, respectively, for the
      "early" arm and 33%, 22%, and 15% for the "late" arm. There were 232 (75%)
      recurrences among those patients whose disease recurred. The proportion who had
      local recurrence within the radiation field was 41% and 39% for "early" and
      "late" treatment arms respectively. The proportion of brain metastases in the
      "late" arm (28%) was significantly higher than in the "early" arm (18%) p = .0425
      Fishers' exact test. CONCLUSION: We conclude that early administration of
      locoregional radiotherapy in a combined modality treatment is superior to late
      consolidative locoregional radiotherapy in limited small cell lung cancer.

PMID- 8276651
TI  - Treatment of stage IE primary lymphoma of bone.
AB  - PURPOSE: A retrospective analysis was performed to assess the efficacy of various
      treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND
      MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of
      bone (single osseous focus) were seen at our institution between the years 1970
      and 1989. Information was obtained regarding each patients' presentation and
      clinical course. The histology was reviewed in all patients. Modern
      immunohistochemical stains were performed on each case with available paraffin
      embedded tissue. RESULTS: The histologic classification of the tumors was as
      follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4
      unclassified. The most common presenting symptom was pain (97%) and the following
      bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of
      the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and
      radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate
      analysis revealed a suggestion of an improved 5-year disease-free survival for
      patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57%
      respectively, p = .08). Multivariate analysis (controlling for extent of initial
      evaluation, extent of pathological evaluation and other potential prognostic
      factors) showed that neither treatment resulted in superior outcome with respect
      to disease-free survival, disease specific survival, or overall survival,
      however, doses of radiation greater than 4000 cGy resulted in improved overall
      survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the
      use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of
      chemotherapy to the radiotherapeutic management may decrease the initial relapse
      rate of some patients. Future studies should address this question.

PMID- 8276652
TI  - Radiation therapy for stage I and IIA testicular seminoma.
AB  - PURPOSE: To review the survival, cure rate, treatment morbidity, and late
      sequelae of histologically confirmed seminoma patients who underwent orchiectomy
      and radiation therapy at the Radiation Oncology Center, Mallinckrodt Institute of
      Radiology, from 1964 to 1988. METHODS AND MATERIALS: There were 128 patients,
      with a median patient age of 37 years (range, 17-79 years). Follow-up ranged from
      1-24 years, with a median of 6.7 years. There were 95 patients with Stage I and
      33 with Stage IIA disease. All patients were treated with orchiectomy followed by
      iliac and paraaortic irradiation (median tumor dose: 2500 cGy for Stage I and
      3400 cGy for Stage IIA patients). Twenty-five of 33 patients with Stage IIA
      disease received prophylactic mediastinal and left supraclavicular irradiation
      (median dose, 2700 cGy). RESULTS: For patients with Stage I disease, 5-year
      disease-free survival, overall survival, and survival corrected for intercurrent
      disease were 97%, 100%, and 100%, respectively. For patients with Stage IIA
      disease, the 5-year disease-free survival, overall survival, and survival
      corrected for intercurrent disease were 93%, 89%, and 97%, respectively. Four
      patients (3%) had recurrences; all were outside the radiation treatment field.
      Three of four were successfully salvaged with chemotherapy and rendered disease
      free; the other patient refused treatment. There were no mediastinal recurrences
      whether prophylactic mediastinal irradiation was administered or not. Bowel
      obstruction and necrosis developed in one patient who received 3363 cGy midplane
      dose to the pelvic and paraaortic areas as well as additional intraperitoneal
      colloidal 198Au (150 mCi) for a ruptured seminoma from an undescended testis.
      CONCLUSION: In summary, radical orchiectomy and irradiation of the iliac and
      paraaortic lymphatics is the treatment of choice for patients with Stage I and
      IIA testicular seminoma.

PMID- 8276653
TI  - Treatment of intracranial ependymomas of children: review of a 15-year
      experience.
AB  - PURPOSE: There are still major controversies in the optimal management of
      children with intracranial ependymomas. To assess the impact of tumor site,
      histology, and treatment, the outcome of children treated at the Institut Gustave
      Roussy was reviewed retrospectively. METHODS AND MATERIALS: Between 1975 and
      1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave
      Roussy for postoperative management of an intracranial ependymoma. Location of
      tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment
      consisted of complete resection in 38, incomplete resection in 38 and biopsy only
      in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33.
      Surviving patients have been followed from 12-197 months with a median of 54
      months. RESULTS: The 5-year actuarial survival and event-free survival are 56%
      and 38%, respectively. Thirty-four patients relapsed from 3-72 months after
      diagnosis (median 25 months). In 20 patients, the only site of failure was the
      original tumor site. Three patients failed locally and at distance, while 10
      others failed only at distance. Survival at 5 years was significantly better for
      patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for
      those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free
      survival at 5 years was superior in patients with complete resection of the tumor
      (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs.
      0%, p < 0.001). Sex and tumor site had no impact on survival or event-free
      survival. There was no difference in survival, event-free survival, or pattern of
      failure between patients treated with local field, whole brain or craniospinal
      irradiation, while severe longterm sequelae were noted predominantly in the
      latter two groups. CONCLUSION: Considering that failures were predominantly local
      and that there was no apparent benefit from prophylactic irradiation, we
      recommend local field irradiation with doses above 50.0 Gy for all children with
      intracranial ependymomas, without meningeal dissemination at diagnosis. Special
      considerations are necessary for children < 3 years of age.

PMID- 8276654
TI  - The prognostic significance of the supraclavicular lymph node metastases in
      breast cancer patients.
AB  - PURPOSE: To define the patterns of failure and outcome of patients presenting
      supraclavicular lymph node involvement and the prognostic significance of
      supraclavicular lymph node involvement. METHODS AND MATERIALS: We reviewed the
      history of 795 breast cancer patients treated at the Department of Radiation
      Therapy, University of Wurzburg between 1978 and 1988. The clinical and
      pathologic features of 21 patients who had ipsilateral supraclavicular lymph node
      metastases at primary diagnosis and 38 patients who presented supraclavicular
      lymph node recurrence during the course of disease were reviewed. These were
      compared with the features of 20 patients who initially had M1 status at primary
      diagnosis and 278 patients who had developed distant metastases in the follow-up
      period. Survival rates were calculated starting from the time of diagnosis of
      supraclavicular involvement respective of distant metastases. RESULTS: Survival
      from appearance of supraclavicular lymph node metastases at primary diagnosis or
      as a recurrence is not different from survival of patients presenting with a
      primary M1 stage or presenting distant metastases during the course of disease.
      Two and 5-year survival rates of patients with supraclavicular lymph node
      involvement at primary diagnosis were 52% and 34% compared to 50% and 16% 2- and
      5-year survival rate of patients with supraclavicular lymph node involvement as a
      recurrence. Patients who presented a primary M1-status had 2- and 5-year survival
      rates of 56% and 24%. Survival of patients with distant metastases calculated
      from the onset of metastatic disease was similar to that of the other three
      groups with a 46% and 16% survival rate at 2 and 5 years. There was no difference
      in survival rates between the four groups. CONCLUSION: The prognostic
      significance of supraclavicular lymph node involvement at primary diagnosis or as
      a relapse is similar, both have the same significance as the first distant
      relapse and are characterized by a poor prognosis.

PMID- 8276655
TI  - The management of histologically unverified presumed cerebral gliomas with
      radiotherapy.
AB  - PURPOSE: To define the natural history, and prognostic factors of patients with
      histologically unverified presumed gliomas diagnosed on CT or MR imaging, and
      treated with external beam radiotherapy. METHODS AND MATERIALS: Retrospective
      review of 111 adults with histologically unverified presumed cerebral glioma
      treated with radiotherapy between 1974 and 1990. Using CT or MRI criteria alone
      41 were presumed low grade, 63 high grade gliomas and 7 were unclassified.
      Survival results were compared to a cohort of 82 adults with histologically
      verified low grade gliomas treated over the same period with surgery and
      radiotherapy. RESULTS: The 5 year survival probability of the whole cohort was
      31%. Age, performance status, and the degree of contrast enhancement were
      independent prognostic factors for survival. Patients with presumed low grade
      glioma had a 5 year survival of 41% compared to 52% for patients with verified
      low grade glioma. After correction for prognostic factors no significant
      difference was found in the survival between patients with verified and
      unverified low grade tumors. One of 15 cases with subsequent histology, obtained
      at autopsy or salvage surgery, had nonglial pathology. CONCLUSION: Patients
      diagnosed on the basis of clinical features and imaging as having presumed glioma
      have similar natural history and clinical behavior after treatment with
      radiotherapy to those with histologically confirmed gliomas. However, the results
      should not be taken as justification for avoiding biopsy. A proportion of
      patients may have nonglial pathology and new more effective treatment strategies
      for patients with glial tumors can only evolve on the basis of full diagnostic
      information including pathology.

PMID- 8276656
TI  - Therapy monitoring in human and canine soft tissue sarcomas using magnetic
      resonance imaging and spectroscopy.
AB  - PURPOSE: The goals of this study were to determine whether magnetic resonance
      parameters (a) can identify early during therapy those patients most likely to
      respond to hyperthermia and radiotherapy, (b) can provide prior to or early
      during therapy information about the temperature distributions which can be
      obtained in patients receiving hyperthermia, and (c) can provide an understanding
      of the effects of hyperthermia on tumor metabolic status. METHODS AND MATERIALS:
      Twenty-one human patients and 10 canine patients with soft tissue sarcomas
      treated with preoperative hyperthermia and radiation had a series of magnetic
      resonance imaging and phosphorous spectroscopy studies done. To address the goals
      for both the human and canine populations, changes in mean T2 relaxation times,
      pH, and various phosphometabolite ratios from the pretreatment (Study 1) to the
      post first hyperthermia study (Study 2) were correlated with treatment outcome;
      pretreatment magnetic resonance parameters and changes in magnetic resonance
      parameters (Study 2-Study 1) were compared with various cumulative thermal
      descriptors; and thermal descriptors of the first hyperthermia were compared with
      changes in magnetic resonance phosphometabolite ratios. RESULTS: A decrease in
      adenosine triphosphate/phosphomonoester from study 1 to study 2 is associated
      with a greater chance of > or = 95% necrosis in surgical resected tumors from
      human patients, but no significant relationships were observed between changes in
      tumor pH or phosphometabolite ratios and time to local failure in dogs.
      Pretreatment magnetic resonance parameters correlated with various thermal dose
      descriptors in canines but not in humans. Change in adenosine
      triphosphate/inorganic phosphate and phosphomonoester signal to noise ratio
      correlated with cumulative thermal descriptors in dogs and humans, respectively.
      In dogs only, increases in thermal dose resulted in decreases in high energy
      phosphometabolites. CONCLUSION: Changes in magnetic resonance parameters early
      during therapy may be predictive of treatment outcome. Pretreatment and changes
      in magnetic resonance parameters appear to predict how well a tumor will be
      heated during hyperthermia. Magnetic resonance spectroscopy also appears to be a
      useful tool to study the effects of various thermal doses on tumor metabolic
      status.

PMID- 8276657
TI  - HSP 70 synthesis in clinical hyperthermia patients: preliminary results of a new
      technique.
AB  - PURPOSE: Although thermotolerance may be an important variable in clinical
      hyperthermia, few means have been described to measure its effect or duration in
      the clinical setting. This study was undertaken to determine if heat shock
      protein 70 could be used as an assay to predict the presence of retained
      thermotolerance in human tumors. METHODS AND MATERIALS: Tissue samples were
      obtained from patients undergoing hyperthermia and assayed for heat shock protein
      70 synthesis. Eight patients having advanced, persistent, or recurrent malignant
      tumors had open-ended thermometry catheters placed into the lesion being heated.
      Through these catheters, tissue samples were obtained using a fine needle
      aspiration technique. Attempts were made to obtain samples before and after the
      first three heat treatments. Some samples were labeled immediately with
      radioactive methionine (35S) at 37 degrees C for 4-8 hr, others were given a test
      heat dose in vitro and then labeled. Protein synthesis profiles were analyzed by
      gel electrophoresis and autoradiography. RESULTS: Preliminary results show that
      it is possible to obtain tissue from hyperthermia patients in a safe and
      practical manner, that the rate of heat shock protein 70 synthesis can be
      measured in a variety of tumors, and that the persistence of thermotolerance in
      the clinical setting can be shown by the inability to reinduce heat shock protein
      70 synthesis. CONCLUSION: The measurement of heat shock protein 70 using the
      described technique may provide an assay for retained thermotolerance in clinical
      hyperthermia. Technical difficulties which need to be addressed include obtaining
      sufficient tissue in all patients, confirming the presence of tumor in the
      obtained tissue, and obtaining tissue at more frequent intervals to best
      determine the kinetics of thermotolerance.

PMID- 8276658
TI  - Hyperfractionated craniospinal radiation therapy for primitive neuroectodermal
      tumors: early results of a pilot study.
AB  - PURPOSE: To report the early results of hyperfractionated craniospinal radiation
      therapy with and without adjuvant chemotherapy for primitive neuroectodermal
      brain tumors (PNETs). METHODS AND MATERIALS: Thirty-nine patients with PNETs were
      classified as good-risk (23) or poor-risk (16), based on postoperative magnetic
      resonance imaging and a cytological examination of cerebrospinal fluid. All
      patients received hyperfractionated craniospinal radiation therapy; poor-risk
      patients subsequently received adjuvant chemotherapy with cisplatin, lomustine,
      and vincristine. The first six patients received 72 Gy to the primary tumor site
      and 24 Gy to the rest of the craniospinal axis. Subsequent patients received 30
      Gy to the craniospinal axis. RESULTS: During a median of 1.9 years of follow-up
      (range 4 months to 3.5 years), there have been ten treatment failures in 39
      patients, five in the good-risk group and five in the poor-risk group. Three
      failures occurred in the primary tumor site in areas that received 72 Gy; two
      were in poor-risk patients with residual disease after surgery; one was in a good
      risk patient who had a gross total resection. Three failures occurred in the
      spine and craniospinal fluid of patients treated with 24 Gy. Four occurred in
      areas treated to 30 Gy; two of these were in areas thought to be undertreated
      because of treatment planning errors. Adjuvant chemotherapy was difficult to give
      to poor-risk patients because of poor bone marrow recovery, even with relatively
      low doses of lomustine (75 mg/m2). CONCLUSION: We think a dose of 24 Gy to the
      craniospinal axis is inappropriate because three of the six patients who received
      it had treatment failures outside the primary site. Whether 30 Gy is an
      appropriate dose for good-risk patients is still unclear. Even after a dose of 30
      Gy, chemotherapy was difficult to give; this potentially limits the impact of
      adjuvant chemotherapy in poor-risk patients. Further follow-up is necessary to
      evaluate the use of hyperfractionated radiation therapy alone or with
      chemotherapy in patients with PNETs.

PMID- 8276659
TI  - Prospective phase I evaluation of radiation therapy, 5-fluorouracil, and
      levamisole in locally advanced gastrointestinal cancer.
AB  - PURPOSE: A recent clinical trial in patients with resected node-positive colon
      cancer demonstrated a clear survival advantage for patients treated with adjuvant
      5-fluorouracil and levamisole. This finding led to interest in development of a
      Phase III trial comparing 5-fluorouracil and levamisole with 5-fluorouracil,
      levamisole, and radiation therapy in colon cancer patients at high risk for local
      recurrence. A prospective evaluation of 5-fluorouracil, levamisole, and radiation
      therapy was undertaken with the goal of establishing a satisfactorily tolerated
      regimen. METHODS AND MATERIALS: Fifteen patients were studied who had locally
      advanced or locally recurrent upper abdominal gastrointestinal cancer (11
      patients) or large bowel cancer confined to the pelvis (4 patients). The tumor
      and regional lymph nodes received 45 Gy in 25 fractions. Patients with pelvic
      tumors subsequently were treated with a radiation boost of 5.4-9 Gy in 3-5
      fractions. Systemic therapy consisted of 5-fluorouracil, 450 mg/m2, given
      intravenously for 3 consecutive days during the first and last weeks of radiation
      therapy. Levamisole, 50 mg, given orally 3 times daily was used for 3 consecutive
      days concurrent with initiation of radiation therapy and 5-fluorouracil, at the
      beginning of the third week of radiation therapy, and concurrent with the final 3
      day course of 5-fluorouracil. RESULTS: Therapy was generally well tolerated. In
      two patients, > or = grade 3 nonhematologic toxicity developed and consisted of
      transient small bowel obstruction in one and severe nausea and vomiting related
      to levamisole administration in another. One patient experienced grade 3
      hematologic toxicity with a leukocyte count nadir of 1,600 cells/microL.
      CONCLUSIONS: These results are similar to the toxicity profile reported elsewhere
      for radiation therapy and 5-fluorouracil. The addition of levamisole to radiation
      therapy and 5-fluorouracil does not appear to increase toxicity significantly.

PMID- 8276660
TI  - Recurrent carcinoma of the cervix exclusively in the paraaortic nodes following
      radiation therapy.
AB  - PURPOSE: This is a retrospective analysis of 1211 patients with invasive
      carcinoma of the uterine cervix treated with irradiation alone at the
      Mallinckrodt Institute of Radiology from 1959 through 1986, of whom 20 developed
      their first recurrence exclusively in the paraaortic lymph nodes. METHODS AND
      MATERIALS: The incidence of clinically/radiographically detected paraaortic node
      recurrence by stage at original diagnosis was 1.8% in Stage IB (7/384 patients),
      2.3% in Stage IIA (3/128 patients), 1.4% in Stage IIB (5/353 patients), 1.4% in
      Stage III (4/292 patients), and 5% in Stage IVA (1/20 patients). Forty-five
      percent of para-aortic node recurrences were observed within the first 12 months
      after initial diagnosis and 75% within the first 2 years. Sciatic pain, leg
      edema, and hydronephrosis were identified in most patients. Patients were treated
      with external irradiation only to the paraaortic lymph nodes. RESULTS: All
      patients died within 2 years of paraaortic recurrence. Median survival for the
      entire group was 8.7 months. Median survival was 7.5 months for those failing
      within 24 months of the original diagnosis compared with 17.8 months for those
      failing after 24 months from original diagnosis (p = 0.09). Patients who received
      > 4500 cGy had a median survival of 14.2 months compared with 7.1 months for
      those treated with < 4500 cGy to the paraaortic recurrence (p = 0.004). Forty
      five percent of patients developed mild to moderate nausea during paraaortic
      irradiation; however, no severe complications from the radiation therapy were
      noted. CONCLUSION: Sciatic pain, leg edema, and hydronephrosis commonly occur in
      patients with paraaortic node recurrence. The presence of these symptoms in a
      patient with a history of carcinoma of the cervix should initiate an aggressive
      evaluation.

PMID- 8276661
TI  - Vaginal template implant for cervical carcinoma with vaginal stenosis or
      inadvertent diagnosis after hysterectomy.
AB  - PURPOSE: For cervical carcinoma patients with poor geometry for conventional
      intracavitary radiotherapy, a simple vaginal template for interstitial
      implantation as a substitute was used. This template has also been used to treat
      patients who had hysterectomy done without knowledge of an early tumor in the
      cervix, and for patients with recurrent disease. This is a report of the
      treatment results. METHODS AND MATERIAL: A total of 21 patients were treated over
      from July 1987 to June 1991 with this vaginal template implant forming part of
      the treatment, 12 of these were performed for vaginal stenosis. The applicator
      consists of a front piece and an end piece. Holes were drilled in the front piece
      to guide the implantation of the cervix or vaginal vault. The diameter of
      applicators varied from 2 cm to 3.5 cm. Depending on the diameter of the
      applicators, six to eight needles on the periphery, or eight peripheral plus one
      central needle were used. The activity of the needles were around 8 mCi with a
      total length of 5.5 cm. The end piece was locked onto the front piece by a
      bayonet-type locking device. The purpose of the end piece was two-fold: to make
      up the length of the whole applicator to fit the vagina and to keep the implanted
      needles in place without being extruded. The implantation was performed under
      general anesthesia. RESULTS: One of the twelve patients treated with the vaginal
      template implant for vaginal stenosis had relapsed centrally but subsequently
      died of intercurrent disease. Two other patients died of intercurrent disease at
      26.2 and 41.9 months, respectively, without evidence of relapse. Nine other
      patients had been followed with no evidence of local relapse for 23.7 to 54.6
      months. CONCLUSION: This vaginal template implantation is a satisfactory means of
      treating patients with vaginal stenosis and those who had hysterectomy done
      without knowledge of an early tumor in cervix.

PMID- 8276662
TI  - Photodynamic therapy--an alternative pathway in the treatment of recurrent breast
      cancer.
AB  - PURPOSE: Validity of photodynamic therapy for treatment of recurrent breast
      cancer. METHODS AND MATERIALS: Patients were intravenously administered with a
      metal-free haematoporphyrine derivative for tumor sensibilization. For
      irradiation both monochromatic and white light was used. Monochromatic light at a
      wavelength of 632 nm was supplied by an Argon-Dye laser, whereas a halogen lamp
      provided white light. Narrowband red light came into use in case of one patient.
      Therapy included recurrent diseases of breast carcinoma, especially disseminary
      skin metastases, local recurrences, and lymphangiosis. Classical pretreatment was
      ineffective for the therapeuted patient group. RESULTS: The healing potency of
      photodynamic therapy for our patient group is enumerated in detail. No
      differences in the therapeutic effect were seen using either Argon Dye laser or
      noncoherent light sources. CONCLUSION: Photodynamic therapy appears to be a
      valuable treatment to classical therapeutic intervention providing a selective
      destruction of tumor cells without further affecting life quality.

PMID- 8276664
TI  - Static field conformal stereotactic radiosurgery: physical techniques.
AB  - PURPOSE: Lesions in the head that are irregularly shaped or large present
      challenges for radiosurgical treatment by conventional techniques. Single, large
      circular fields may treat normal tissue volumes. Multiple shot or multiple
      isocenter treatment plans provide better conformation to the target than a single
      field, but may be difficult to plan and/or treat. As an alternative to these
      conventions, we are developing static field, conformal stereotactic radiosurgery.
      In this technique a finite number of fixed, shaped, linear accelerator fields are
      used to irradiate the target. METHODS AND MATERIALS: Computer simulations were
      performed for a four-path arc and fixed field techniques and evaluated with dose
      distributions and dose volume histograms. Beam geometries are defined with a 3-D
      treatment planning system with beam's eye view capabilities. Equipment for
      treatment delivery has been designed, including a head frame/support stand
      assembly and a method for manufacturing the required custom collimators. RESULTS:
      Isodose distributions and dose volume histograms show that beam geometries with
      seven or more fields provide target dose distributions equivalent to the arc
      treatment, but with small increases in peripheral dose. Dose homogeneity across
      the target volume increases as the solid angle of irradiation is increased. For a
      hemispherical target, the four-path arc and shaped, static fields provide equal
      target coverage while the shaped fields treat a smaller high-dose volume.
      CONCLUSION: Shaped, static fields are an alternative to single isocenter arc
      radiosurgery and result in smaller volumes at high dose. This smaller volume
      could translate into sparing for normal adjacent tissues that would otherwise be
      treated.

PMID- 8276663
TI  - Larynx motion associated with swallowing during radiation therapy.
AB  - PURPOSE: A basis is presented for predicting the reduction in radiation dose to
      the larynx attributable to swallowing during radiation therapy treatment. METHODS
      AND MATERIALS: Laryngeal movement associated with swallowing can occur during
      radiation therapy even when the patient's head is immobilized. Data on the extent
      and timing of laryngeal motions and the frequency of swallowing were used to
      predict the effect such motion would have on accuracy of radiation dose to the
      larynx. RESULTS: In a nontracheostomized adult the larynx elevates approximately
      2 cm during a swallow and moves anteriorly less than 1 cm. The normal frequency
      of swallowing in the supine position is once every 1-2 min. During therapy, the
      likelihood of a swallow occurring during an irradiation interval depended on the
      duration of the interval. For irradiation intervals less than 2 min long the
      ratio of number of swallows to number of intervals was 0.27. For irradiation
      intervals between 2-3 min long the ratio was 1.76. Based on conservative
      estimates of radiation field dimensions, larynx motion, and incidence of
      swallowing, the reduction in radiation dose attributable to swallowing during
      treatment would be approximately 0.5%. CONCLUSION: With small fields the total
      dose is only decreased by 0.5% with swallowing, so the change in the total dose
      is insignificant.

PMID- 8276665
TI  - Precision and accuracy of stereotactic convergent beam irradiations from a linear
      accelerator.
AB  - PURPOSE: The accuracy and the precision for radiosurgery procedures at linear
      accelerator facilities were investigated. METHODS AND MATERIALS: The technique of
      convergent beam irradiation, that is a series of successive isocentric arc
      irradiations, is specifically considered in this paper. Accuracy and precision
      depend on a sequence of methods and equipment among which localization of the
      target, patient alignment, and the dose delivery are the most critical steps. The
      purpose of the investigation was to quantitatively assess their contribution to
      the overall accuracy. The definitions and methods used to quantify and control
      accuracy are described. Measurements were carried out at a phantom to analyze the
      localization and positioning errors. Errors which may occur with the dose
      delivery technique were studied by a computer simulation. RESULTS: The
      calculations showed that these errors are not the main contributors to the
      overall accuracy as long as the linac inaccuracies are in the order or less than
      1 mm. The accuracy found in the localization and positioning methods was less
      than 1 mm. CONCLUSION: It was concluded that an overall accuracy in the order of
      1 mm can be obtained also under routine conditions. The great importance of
      adequate quality control is emphasized.

PMID- 8276666
TI  - Systematic analysis of errors in target localization and treatment delivery in
      stereotactic radiosurgery (SRS).
AB  - PURPOSE: To systematically analyze the spatial uncertainties associated with each
      step of the stereotactic radiosurgery (SRS) procedure and the overall spatial
      accuracy in the treatment delivery. METHODS AND MATERIALS: A special test device
      has been designed and fabricated to permit accurate simulation, localization and
      treatment portal verification of a SRS target. This device with simulated targets
      dispersed in 3-D space can be rigidly attached to the BRW CT or angio frame for
      localization, to the BRW phantom base for target coordinate determination, and to
      the floor stand for portal verification. The setup allows evaluation of the
      accuracy of each procedure separately as well as the overall accuracy in the
      delivery of SRS treatment. RESULTS: Biplanar film localizations reveal a
      systematic error in the phantom base pointer of the order of 0.1 mm that is
      applied as a correction to the measured target coordinates. Targets localized by
      planar film angiography had a mean positional error of 0.38 +/- 0.1 mm compared
      to 1.0 +/- 0.7 mm for digital angiographic localization. The positional accuracy
      associated with CT localization was superior when a 2 mm vs. 4 mm slice thickness
      was used (0.9 +/- 0.3 mm vs. 1.6 +/- 0.5 mm error). Cumulative mean errors,
      including inaccuracies associated with treatment setup, were 1.0 +/- 0.4 mm for
      radiographic localization, 1.2 +/- 0.5 mm for CT with a 512 x 512 matrix and 2 mm
      slice thickness, and 2.0 +/- 0.6 mm for CT at a 4 mm slice thickness (256 x 256
      matrix). Larger errors would be expected in the clinical setting. CONCLUSION:
      Spatial errors in stereotactic radiosurgery are best estimated using a systematic
      approach to isolate independent contributing factors. The accuracy in target
      localization determines the overall accuracy of SRS procedure, provided the
      mechanical accuracy of the treatment apparatus is assured. Biplanar treatment
      portal verification with a fiducial localization frame is an accurate method of
      verifying the target coordinates before delivering treatment.

PMID- 8276667
TI  - Treatment volume from total reference air kerma (TRAK) in intracavitory
      applications and its comparison with ICRU reference volume.
AB  - PURPOSE: A systematic dosimetry study conforming to International Commission on
      Radiation Units and Measurements Report Number 38, was carried out for, cancer of
      Cervix Stage I and II cases at Tata Memorial Hospital. METHODS AND MATERIALS: The
      reference Volume dimension were noted for each applicator. Also 3-D dosimetry was
      performed for selected cases, and actual geometric volume enclosed by various
      isodose surfaces were obtained. A relation was derived, which gave the volume
      enclosed by any isodose surface as a function of total reference air kerma of the
      sources in the applicator. The volume enclosed by reference isodose surface was
      compared with the product of its dimensions height, width, and thickness.
      RESULTS: The volume enclosed by any isodose surface of an intracavitary
      application can be easily derived from total reference air kerma of the sources
      within the applicator. CONCLUSION: Ratio of the volume enclosed by reference
      isodose surface with the product of its dimensions (HWT) could be a predictive
      parameter for clinical outcome, besides the reference volume specified by the
      report.

PMID- 8276668
TI  - A new method for determining dose rate distribution from radioimmuno-therapy
      using radiochromic media.
AB  - PURPOSE: To describe and evaluate a new, simple, inexpensive method for directly
      measuring the radiation dose and its spatial distribution generated from
      explanted tissues of animals previously injected with radiolabeled
      immunoconjugates or other agents. METHODS AND MATERIALS: This technique uses the
      newly developed radiochromic dye medium (Gafchromic) which responds reproducibly
      for therapeutic dose exposures, has high spatial resolution, does not require
      film processing, and is relatively insensitive to ambient light. We have
      evaluated the dose distribution from LS174T tumors and selected normal tissues in
      nude mice previously injected with 90Y labeled anti-carcinoembrionic antigen
      antibodies. Individual tissues from sacrificed animals are halved and the flat
      section of the tissue is placed onto the dosimetry media and then frozen. The
      dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from
      the frozen tissues. The relative darkening of the dosimetry medium depends on the
      dose deposited in the film. The dosimetry medium is scanned with a commercial
      flatbed scanner and the image intensity is digitally stored and quantitatively
      analyzed. Isodose curves are generated and compared to the actual tissue outline.
      RESULTS: The absorbed dose distribution due to 90Y exposure show only slight
      gradients in the interior of the tissue, with a markedly decreasing dose near the
      edges of the tissue. In addition, the isodose curves follow the tissue outline
      except in regions having radii of curvature smaller than the range of the beta
      particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its
      curvature, are important in determining the minimum dose delivered to the tumor
      by radiation from 90Y monoclonal antibodies, and hence in evaluating the tumor
      response to the radiation. The dose and spatial dose distribution were calculated
      assuming that the total 90Y activity is distributed uniformly throughout a half
      ellipsoid. The calculated spatial dose distributions for the half ellipsoids were
      similar to those observed from the dosimetry media that had been exposed to
      radioactivity contained in the tumors. CONCLUSION: This method provides direct
      dose evaluation without elaborate summary calculations based on activity
      measurements from serial slices. The measured radiation dose actually indicates
      the dose rate at the time of animal sacrifice. Quantitative analysis of radiation
      emitted from the tissues is relatively fast, making it feasible to examine a
      number of tissues under a variety of conditions.

PMID- 8276669
TI  - Study on the reference dose level in radiotherapy treatment planning.
AB  - PURPOSE: The reference dose level of the dose distribution in the tumor volume is
      studied. METHODS AND MATERIALS: The study is performed using a formula based on
      the Linear Quadratic (LQ) model. The calculated reference dose level to which the
      prescribed dose must be referred, for the eradication of a homogeneous tumor, is
      investigated by varying the dose distribution, that is, the dose volume histogram
      shape, its range, the prescribed total dose, the fraction size and the linear
      quadratic model parameters, alpha and beta. RESULTS: For all the simulated dose
      volume histograms the calculated reference dose level is lower than the mean dose
      level, depending on the range of dose variation and the considered tumor
      sensitivity. When the dose nonuniformity is not too great the reference dose
      level is very near to the mean dose level; when the inhomogeneity of dose
      distribution is high the reference level is clearly lower than the mean level but
      not necessarily equal to the minimum level in the tumor. For the dose volume
      histograms derived from the actual dose distributions obtained from a two
      tangential beams technique, a four beams technique and a moving beam technique,
      the reference levels are calculated and compared with the ICRU 29 reference point
      dose level. In two cases the reference levels are lower than the level at the
      ICRU 29 reference point. In the case of the four beams technique, the two levels
      are equal. CONCLUSION: These theoretical results show the possibility of
      administering the prescribed dose to a dose level higher than the minimum in the
      tumor, with the same value of Tumor Control Probability (TCP) as the one
      corresponding to a uniform tumor irradiation. The application of the proposed
      study can offer a general support to the choice of the reference dose level,
      based on the actual dose distribution in the tumor volume.

PMID- 8276670
TI  - Current radiosurgery practice: results of an ASTRO survey. Task Force on
      Stereotactic Radiosurgery, American Society for Therapeutic Radiology and
      Oncology.
AB  - PURPOSE: Although there is increasing interest in radiosurgery, little
      quantitative data regarding current patterns of radiosurgery practice are
      available. We developed a radiosurgery questionnaire to obtain information on
      radiosurgery practice. METHODS AND MATERIALS: We distributed the questionnaire to
      the entire membership of the American Society of Therapeutic Radiology and
      Oncology in early 1993. Responses were obtained from 74 facilities that practice
      radiosurgery, corresponding to over 6000 treatments carried out since 1983 by 135
      radiation oncologists and 130 physicists. RESULTS: Most respondents were found to
      work within a multidisciplinary team, consisting of the following specialists
      (average hours devoted per patient on day of treatment in parentheses): radiation
      oncologist (3.8), neurosurgeon (3.2), physicist (6.1), radiologist (0.7), nurse
      (2.7), other (3.0). On average, neurosurgeons and nurses who perform Gamma Knife
      radiosurgery devote significantly more time-per-patient on the day of treatment
      than their peers who perform linac radiosurgery. On average, less experienced
      radiation oncologists and physicists (< or = 24 months experience, or < or = 50
      patients treated) devote significantly more time-per-patient on the day of
      treatment than their more experienced peers. Although there are many more linac
      radiosurgery facilities than Gamma Knife facilities, on average the number of
      patients treated per month per facility is significantly larger at the latter. On
      average, follow-up responsibilities are nearly equally shared by radiation
      oncologists and neurosurgeons, except at Gamma Knife facilities, where
      neurosurgeons assume a larger percentage of follow-up responsibility. The
      percentages of patients treated at linac facilities for metastases or primary CNS
      malignancy are larger than the corresponding percentages at Gamma Knife
      facilities; the opposite is true for arteriovenous malformation, acoustic
      neuroma, and meningioma. CONCLUSION: Current radiosurgery practice usually
      involves a team approach, with participation of specialists from radiation
      oncology, neurosurgery, physics, radiology, and nursing. The average number of
      M.D. and Ph.D. hours required per treatment on the day of radiosurgery is high.

PMID- 8276671
TI  - Consensus statement on stereotactic radiosurgery quality improvement. The
      American Society for Therapeutic Radiology and Oncology, Task Force on
      Stereotactic Radiosurgery and the American Association of Neurological Surgeons,
      Task Force on Stereotactic Radiosurgery.

PMID- 8276672
TI  - Cisplatin and radiation in the treatment of tumors of the central nervous system:
      pharmacological considerations and results of early studies.
AB  - PURPOSE: To review the human central nervous system pharmacology of cisplatin,
      factors that affect cisplatin uptake in tumors, and use alone and with radiation
      for the treatment of primary brain tumors. METHODS AND MATERIALS: The authors
      review their own prior published and unpublished experience and data published by
      other groups on the above issues. RESULTS: Cisplatin is one of the most active
      chemotherapy drugs available for the treatment of solid tumors. It is synergistic
      with several other agents, including radiation. While it attains only low
      concentrations in the normal central nervous system, concentrations and plasma
      tissue transfer constants for human intracerebral tumors are comparable to those
      in extracerebral tumors. Tumor type appears to be a more important determinant of
      platinum concentration than is tumor location, and gliomas do achieve lower
      concentrations than do other intracerebral or extracerebral tumors. Several other
      factors have also been identified that correlate with concentrations of cisplatin
      achieved in human tumors. While cisplatin alone and in combination with other
      drugs does have some degree of efficacy against primary brain tumors, combining
      it with cranial irradiation has generally not resulted in any substantial
      improvement in outcome to date, although some individual studies have been
      somewhat encouraging. New approaches are currently under investigation.
      CONCLUSION: Human pharmacology studies provide a rationale for use of cisplatin
      in the treatment of human brain tumors, and human and in vitro studies suggest
      some manipulations that might potentially further augment tumor platinum
      concentrations. While clinical studies suggest that cisplatin combinations may be
      of some value vs. human primary brain tumors and brain metastases, and while in
      vitro studies suggest that cisplatin potentiates radiation efficacy, no
      combination of cisplatin plus radiation yet tested has appeared to be superior to
      radiation alone.

PMID- 8276673
TI  - Timing of radiotherapy in small cell lung cancer.

PMID- 8276674
TI  - Alternative management options to radiation therapy for stage I and IIA
      testicular seminoma.

PMID- 8276675
TI  - Should patients with histologically unverified brain tumors receive cranial
      irradiation?

PMID- 8276676
TI  - Stereotactic radiosurgery quality improvement: interdepartmental collaboration.

PMID- 8276677
TI  - Beware of the BID bandwagon.

PMID- 8276678
TI  - One dose more, one dose less.

PMID- 8276679
TI  - Verification of vertex fields for radiotherapy of brain tumors.

PMID- 8276681
TI  - [Quality assurance--a midwife's concern].

PMID- 8276680
TI  - Regarding Keane et al.'s randomized trial comparing radiation alone to
      concomitant infusional 5-flurorouracil, bolus mitomycin-C and split-course
      radiation.

PMID- 8276682
TI  - [HELLP syndrome--how can it be diagnosed during pregnancy?].

PMID- 8276683
TI  - [Does episiotomy prevent perineal trauma and pelvic floor relaxation?].

PMID- 8276684
TI  - [Episiotomy and perineal lesions in spontaneous vaginal deliveries].

PMID- 8276685
TI  - [Risk preventing activities in the delivery department--supervisory project
      within the Social Welfare Board].

PMID- 8276686
TI  - [Bearing children is a natural process!].

PMID- 8276687
TI  - [Invisible midwives--get up to fight].

PMID- 8276688
TI  - [Changing in the smoking and drinking habits of future fathers from the onset of
      their wives' pregnancies].

PMID- 8276689
TI  - [Reproductive health in an international perspective].

PMID- 8276690
TI  - Compounding forum: FDA-CVM hears veterinarians' views.

PMID- 8276691
TI  - Making essential drugs available.

PMID- 8276692
TI  - Concerned about study on euthanasia.

PMID- 8276693
TI  - Diagnosis and treatment of Halicephalobus (syn micronema) deletrix infection.

PMID- 8276694
TI  - Milk and dairy beef quality assurance program: a food safety issue.

PMID- 8276695
TI  - How can each of us be trustworthy?

PMID- 8276696
TI  - Changes and challenges in feline nutrition.

PMID- 8276697
TI  - What is your diagnosis? Penetrating foreign body in a horse causing delayed wound
      healing and a chronic draining tract.

PMID- 8276698
TI  - Mastitis, metritis, traumatic reticuloperitonitis, and suspected fungal rumenitis
      in a cow.

PMID- 8276699
TI  - Distribution of US veterinarians by gender, 1990 and 1992.

PMID- 8276700
TI  - Cytologic analysis of bronchoalveolar lavage fluid from 47 dogs with multicentric
      malignant lymphoma.
AB  - Bronchoalveolar lavage (BAL) was performed in 47 dogs with multicentric malignant
      lymphoma (ML). Cytologic results were evaluated, and ability to detect pulmonary
      involvement with ML, using BAL, was compared with ability to detect pulmonary
      involvement, using thoracic radiography and tracheal wash. Lung lobes were
      considered to be involved with ML on the basis of BAL fluid findings if
      morphologically abnormal lymphocytes were present in the fluid. Total nucleated
      cell count, relative lymphocyte count, and absolute lymphocyte count were greater
      (P < 0.001) in BAL fluid from dogs with multicentric ML than in BAL fluid from
      histologically normal dogs. Pulmonary involvement with ML was detected by BAL
      fluid cytologic examination in 89 of 135 lung lobes lavaged (66%). Lung lobes
      involved with ML were from 31 of the 47 dogs with multicentric ML (66%).
      Radiographic abnormalities supportive of pulmonary parenchymal involvement with
      ML were detected in 16 of the 47 dogs (34%). Of these 16 dogs, 15 (94%) had
      pulmonary involvement with ML on the basis of BAL fluid cytologic findings.
      Tracheal wash fluid contained abnormal lymphocytes in 4 of 41 dogs (10%). In all
      4 dogs, BAL fluid also contained abnormal lymphocytes. Cytologic evaluation of
      BAL fluid was more sensitive in detecting pulmonary involvement with ML, compared
      with radiographic evaluation of the lungs or tracheal wash.

PMID- 8276701
TI  - Clinical efficacy of milbemycin oxime in the treatment of generalized demodicosis
      in adult dogs.
AB  - Thirty adult dogs with chronic generalized demodicosis were treated with oral
      administration of milbemycin oxime (0.52 to 3.8 mg/kg of body weight, q 24 h).
      Results of skin scrapings were used to determine whether administration of
      milbemycin should be continued or discontinued. Dogs that were free of clinical
      signs of demodicosis 12 months after administration of milbemycin was
      discontinued were considered cured. Sixteen dogs were cured, 5 dogs were never
      cleared of mites, and 9 dogs were cleared of mites, but relapsed after
      administration of milbemycin was discontinued. Adverse effects of milbemycin were
      rare and transient.

PMID- 8276702
TI  - Synovial sarcoma in a cat.
AB  - A 9-year-old male castrated cat was examined because of right forelimb lameness
      of 2 months' duration. The right cubital area was large, and the range of motion
      of the cubital joint was limited. Radiography revealed a mild periosteal reaction
      of the humerus, radius, and ulna. There was cortical remodeling of the distal
      portion of the humerus and punctate osteolysis within the proximal portion of the
      ulna. Arthrocentesis was performed and neoplastic cells were found, which led to
      a tentative diagnosis of osteogenic sarcoma or synovial cell sarcoma. Histologic
      diagnosis of synovial cell sarcoma was made after amputation of the limb.

PMID- 8276703
TI  - Primary suprasellar germ cell tumor in a dog.
AB  - A 5-year-old female Rottweiler was examined because of a history of progressive
      CNS depression and apparent blindness. Findings included retinal degeneration and
      cranial nerve deficits as well as pronounced hypercholesterolemia and
      bradycardia. At necropsy, a 3-cm soft, tan mass was found on the ventral surface
      of the rostral portion of the brain, encompassing the hypophysis and filling the
      sella tursica. Histologic examination of tumor sections identified 3 distinct
      cell types. The location and histologic features of the solitary tumor were most
      consistent with classification as a primary intracranial germ cell tumor.

PMID- 8276704
TI  - Suspected malignant hyperthermia syndrome in a miniature pot-bellied pig
      anesthetized with isoflurane.
AB  - Hyperthermia developed in a 7-week-old Vietnamese pot-bellied pig after
      isoflurane anesthesia for routine ovariohysterectomy. Shivering and a sudden
      increase in heart rate were noticed 90 minutes after anesthetic induction, both
      of which persisted throughout the remaining anesthetic period. Rectal temperature
      increased from 37 C immediately after anesthetic recovery to a peak of 41.5 C,
      and remained high for 18 hours. Treatment included external cooling and treatment
      with dantrolene sodium. Malignant hyperthermia was suspected to be the cause of
      the clinical signs in this pig, but specific tests to support this diagnosis were
      not performed. This report illustrates that hyperthermia may develop in this
      breed of swine during isoflurane anesthesia, and rectal temperature should be
      monitored during and after the anesthetic period.

PMID- 8276705
TI  - Prognosis after surgical excision of cerebral meningiomas in cats: 17 cases (1986
      1992).
AB  - Long-term follow-up information was obtained for 17 cats with cerebral
      meningiomas treated by surgical excision. Three cats died or were euthanatized in
      the immediate postoperative period: 2 cats, because of brain herniation and 1
      cat, because of acute renal failure. In the remaining 14 cats, most clinical
      signs resolved within 1 week of surgery. Three cats (21.4%) had confirmed or
      presumed local tumor recurrence. Two of these cats developed recurrent neurologic
      signs, and died or were euthanatized at 3 and 9 months, respectively, after
      surgery. One cat was euthanatized for an unrelated problem 72 months after
      surgery, and on postmortem examination, had a recurrent meningioma at the surgery
      site. The remaining 11 cats (78.6%) did not develop evidence of local tumor
      recurrence within follow-up periods ranging from 18 to 47 months (median, 27
      months).

PMID- 8276706
TI  - Evaluation of lidocaine, xylazine, and a combination of lidocaine and xylazine
      for epidural analgesia in llamas.
AB  - Epidural analgesia was achieved at weekly intervals in 6 adults llamas by
      injection of 2% lidocaine, 10% xylazine, and a combination of 2% lidocaine/10%
      xylazine at the sacrococcygeal junction. Analgesia was determined by lack of
      response to pin prick or hemostat pressure in the perineal area. Ataxia could not
      be accurately evaluated because of the llamas' tendency to assume sternal
      recumbency when restrained. Time to onset of analgesia was not different between
      lidocaine (3.16 +/- 0.31 minutes) and lidocaine/xylazine (3.50 +/- 0.56 minutes),
      but results for both groups were different than those for xylazine (20.67 +/-
      3.37 minutes). Duration of analgesia was different among all groups (lidocaine,
      71.0 +/- 6.15 minutes; xylazine, 186.83 +/- 14.86 minutes; lidocaine/xylazine,
      325.83 +/- 29.39 minutes). Mild sedation developed in 4 llamas given xylazine
      alone. Lidocaine/xylazine caused mild sedation in 2 llamas and moderate sedation
      in 1 llama. Significant changes in pulse or respiratory rates were not observed
      among drugs, but changes were observed over time with all drugs. As has been
      reported in other species, lidocaine/xylazine provided rapid onset and prolonged
      duration of analgesia.

PMID- 8276707
TI  - Surgical treatment of egg retention in emus.
AB  - We developed a surgical technique for management of retained eggs in emus.
      Clinical signs associated with egg retention include cessation of laying activity
      or failure to lay eggs, lethargy, anorexia, straining, and passing egg material,
      and diagnosis can be made by external palpation, abdominal radiography, and
      ultrasonography. The retained eggs were removed through a paramedian abdominal
      incision in all birds. One bird was euthanatized at surgery because of severe
      peritonitis resulting from uterine rupture at the site of obstruction by the
      retained egg. Three birds survived and were discharged from the hospital to the
      owners. Egg peritonitis resulting from eggs or egg remnants in the abdominal
      cavity was evident in the birds that survived surgery. Surgery and administration
      of antimicrobials were successful in resolving the peritonitis.

PMID- 8276708
TI  - Severe flea infestation in dairy calves.
AB  - An investigation was conducted of a severe flea infestation in Holstein dairy
      calves. Inspection of the dairy revealed hundreds of cat fleas, Ctenocephalides
      felis, on 23 calves, and thousands of fleas in the barn where the calves were
      housed. During the investigation, > 92,000 fleas were collected from the barn.
      The barn also was inhabited by 30 to 35 flea-infested domesticated and feral
      cats. Several calves appeared emaciated, and analysis of blood samples from 10
      calves revealed that 8 were anemic. A control program was initiated, consisting
      of insecticide and insect-growth regulator treatment of calves and premises,
      along with removal of straw bedding from the barn. In addition, domesticated cats
      were to be treated and feral cats were to be removed by live trapping. Nine weeks
      after a complete control program was initiated, fleas were not evident on calves
      or in the barn.

PMID- 8276709
TI  - Delayed organophosphate neurotoxicosis in four heifers.
AB  - Oil-containing triaryl phosphates induced delayed organophosphate neurotoxicosis
      in 4 dairy heifers. Clinical signs developed 10 to 14 days after exposure and
      included dyspnea, dysuria, polyuria, tympanites, incoordination, hind limb
      weakness with knuckling of the metatarsophalangeal joints, and flaccid paralysis.
      Triaryl phosphate concentrations were high in a specimen of fat from 1 heifer,
      and the fat and 2 waste oil samples used to periodically lubricate a feed bunk
      motor chain had similar triaryl phosphate-like chromatographic profiles. The
      diagnosis of delayed organophosphate neurotoxicosis requires history of exposure
      to a potential toxicant, appropriate histologic evaluation of the CNS and,
      ideally, identification of the toxic agent from appropriately selected animal
      tissues.

PMID- 8276710
TI  - Accuracy and economics of the USDA-licensed enzyme-linked immunosorbent assay for
      bovine paratuberculosis.

PMID- 8276711
TI  - Bioactive glycosphingolipids with differentiation-inducing activity toward
      leukemia cells.

PMID- 8276712
TI  - Why are human cells resistant to malignant cell transformation in vitro?
AB  - Transformation of human cells, both induced and spontaneous, is an extremely rare
      event, whereas rodent cells are relatively easily transformed when treated with a
      single carcinogenic agent. The present review addresses the question of why human
      cells are resistant to malignant transformation in vitro. To facilitate
      understanding of the problem, the process of transformation is divided
      operationally into two phases, i.e. phase I, immortalization; and phase II,
      malignant transformation. In human cells, one-phase transformation, i.e., the
      consecutive occurrence of phases I and II due to the action of a single
      carcinogenic agent, is observed only rarely. Once human cells are immortalized,
      however, malignant transformation by chemical carcinogens or oncogenes proceeds,
      suggesting that for human cells, phase I immortalization is a prerequisite for
      such transformation to take place. To date, about 20 papers have been published
      describing protocols for the two-phase transformation of a variety of human
      epithelial cells and fibroblasts. In most experiments, SV40, human papilloma
      viruses and their transforming genes are utilized for induction of phase I
      (immortalization) followed by the use of chemical carcinogens or activated
      oncogenes for induction of phase II (malignant transformation). Possible
      mechanisms that would render human cells refractory to transformation are
      discussed below.

PMID- 8276714
TI  - A novel renal cell carcinoma susceptibility gene maps on chromosome 10 in the
      Eker rat.
AB  - Hereditary renal cell carcinoma (RC) in the rat, originally reported by Eker in
      1954, is an example of Mendelian dominant predisposition to a specific cancer in
      an experimental animal. We previously reported that this predisposing inherited
      gene is a tumor suppressor gene fitting Knudson's "two-hit" model. This study was
      designed to map the RC susceptibility gene in the Eker rat using backcross
      animals. Our present data clearly show that the RC gene is genetically linked to
      the protamine-1 gene (Lod score = 11.65) and the interleukin-3 gene (Lod score =
      4.13), both of which are located on the proximal part of rat chromosome 10. Rat
      chromosome 10 is currently believed to have no syntenic relationship to human
      chromosome 3p, the presumed site of the putative tumor suppressor gene for human
      RC and the locus of von Hippel Lindau disease (affected patients develop multiple
      RCs). Thus, the Eker rat might have a mutation of a novel tumor suppressor gene
      related to renal carcinogenesis.

PMID- 8276713
TI  - K-ras gene mutation in early ductal lesions induced in a rapid production model
      for pancreatic carcinomas in Syrian hamsters.
AB  - The presence of K-ras gene mutation was examined in experimentally induced
      preneoplastic pancreatic ductal lesions. Syrian hamsters received 70 mg/kg of N
      nitrosobis(2-oxopropyl)amine (BOP) followed by repeated exposure to an
      augmentation pressure regimen consisting of choline-deficient diet combined with
      DL-ethionine and L-methionine and administration of 20 mg/kg BOP. After two
      augmentation pressure cycles, pancreatic ductal cell hyperplasias appeared and
      after three cycles, atypical hyperplasias of pancreatic ductal cells and
      intraductal carcinomas developed. K-ras mutations were detected by single-strand
      conformation polymorphism analysis of polymerase chain reaction products and
      nucleotide sequencing. The results showed that K-ras mutation had occurred in one
      of 9 simple hyperplasias of pancreatic ductal epithelium, in 5 of 9 atypical
      hyperplasias, and in 4 of 8 intraductal carcinomas. The findings thus suggested
      that K-ras is activated in association with very early stage malignant
      transformation of pancreatic ductal cells in hamsters.

PMID- 8276715
TI  - An evaluation of mass screening using fecal occult blood test for colorectal
      cancer in Japan: a case-control study.
AB  - There is as yet no firm evidence showing that mass screening for colorectal
      cancer using fecal occult blood tests (FOBTs) reduces the mortality from this
      cancer. Therefore we evaluated the effectiveness of the screening by a case
      control study in Miyagi Prefecture, Japan. The study included as case subjects 28
      individuals who had died from colorectal cancer and had had an opportunity to
      participate in the mass screening before the date of diagnosis as colorectal
      cancer, and 3 controls for each case subject randomly selected from residents who
      were alive on the date of death of case subjects and matched by sex, age (within
      3 years) and living area using residential files. For each set, i.e., a case
      subject and 3 controls, screening histories before the date of the diagnosis of
      the case as colorectal cancer were examined. Both the case subjects and the
      controls who had participated in the screening at least once within 3 years
      before the date of diagnosis of the case were classified as "screened." The 28
      case subjects consisted of 12 males and 16 females (average age: 60.8 years). The
      odds ratio of death from colorectal cancer for the screened versus the non
      screened persons was 0.24 (95% confidence interval = 0.08-0.76) by the Mantel
      Haenszel method. The present study suggests that mass screening using FOBTs for
      colorectal cancer significantly reduces the mortality from this cancer
      epidemiologically.

PMID- 8276716
TI  - Enhanced growth potential of cultured rabbit tracheal epithelial cells following
      exposure to N-methyl-N'-nitro-N-nitrosoguanidine.
AB  - To establish a standardized model for the transformation of rabbit airway
      epithelial cells, we attempted to transform rabbit tracheal epithelial (RbTE)
      cells in culture with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). RbTE cells,
      harvested by enzymatic digestion from male New Zealand white rabbits, were plated
      onto feeder layers of irradiated 3T3 cells. Control cells proliferated
      exponentially during the 2nd week of culture and reached the plateau phase by the
      3rd week. Cells exposed to MNNG (0.1 microgram/ml) proliferated in a fashion
      similar to the control cells, except that there was some delay before
      proliferation began. The clonogenic activity of RbTE cells rapidly decreased in
      parallel with the increase in cell population equally in the control and MNNG
      groups. During the late plateau phase, cells exposed to MNNG regained clonogenic
      activity, and this compartment size expanded with time, whereas the clonogenic
      activity in control cultures remained below the detectable level. In RbTE cell
      cultures exposed three times to 0.1 microgram/ml MNNG, large, persistent and
      proliferating colonies emerged at a frequency of 1-3 x 10(-2) among the surviving
      clones, whereas all the control cultures eventually became senescent. The MNNG
      induced alteration in the growth potential of RbTE cells, i.e., the extended
      lifespan, and the maintenance and even expansion of clonogenic activity, was
      similar to that of transformed rat tracheal epithelial cells. However, no
      immortal cell line could be established from these growth-altered RbTE cells. We
      therefore concluded that the growth-altered RbTE cells were partially
      transformed.

PMID- 8276718
TI  - Alteration of radiosensitivity of quiescent cell populations in solid tumors
      irradiated with X-rays twice at various intervals.
AB  - 5-Bromo-2'-deoxyuridine (BUdR) was injected into SCC VII or EMT6/KU tumor-bearing
      mice intraperitoneally to label all the proliferating tumor cells. First, the
      mice were irradiated with X-rays at a dose of 10 Gy, followed by a dose of 0-20
      Gy at 0, 12, 24 or 48 h later. During the interval, no BUdR was injected.
      Immediately after the second irradiation, the tumors were excised and
      trypsinized. The micronucleus (MN) frequency in cells without BUdR labeling was
      determined by means of incubation with cytochalasin-B (a cytokinesis-blocker) and
      immunofluorescence staining for BUdR. When the tumors were not pretreated with
      BUdR before the first irradiation, the MN frequency in all tumor cells was
      determined. To determine the labeling indices of SCC VII and EMT6/KU tumors at
      the time of the second irradiation, each group also included mice that were
      continuously administered BUdR until just before the second irradiation using
      mini-osmotic pumps which had been implanted subcutaneously 5 days before the
      first irradiation. The MN frequency of all tumor cell populations obtained
      immediately after the second irradiation decreased in proportion to the increase
      in interval time. However, in both tumor systems, the MN frequency of unlabeled
      cell populations, which could be regarded as quiescent cells in the tumors at the
      time of the first irradiation, was raised with increase in the interval time. In
      addition, the labeling index at the second irradiation was higher than that at
      the first irradiation. These findings support the occurrence of recruitment from
      quiescent to proliferating state during fractionated irradiation.

PMID- 8276717
TI  - Comparison of reversibility of rat forestomach lesions induced by genotoxic and
      non-genotoxic carcinogens.
AB  - Reversibility of forestomach lesions induced by genotoxic and non-genotoxic
      carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats
      were given dietary 0.1% 8-nitroquinoline, dietary 0.4-0.2% 2-(2-furyl)-3-(5-nitro
      2-furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N-methyl-N'
      nitro-N-nitrosoguanidine once a week, or 20 ppm N-methylnitrosourethane in the
      drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2%
      caffeic acid, 2% sesamol or 2% 4-methoxyphenol in the diet as a non-genotoxic
      carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24.
      Half of the remainder were maintained on basal diet alone for an additional 24
      weeks and the other half were given the same chemical for 48 weeks, and then
      killed. Forestomach lesions induced by genotoxic carcinogens did not regress
      after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH),
      but not basal cell hyperplasia (BCH), induced by non-genotoxic carcinogens
      clearly regressed after cessation of insult. SPH labeling indices in the non
      genotoxic carcinogen-treated cases decreased after removal of the carcinogenic
      stimulus whereas BCH values were low irrespective of treatment. Atypical
      hyperplasia (AH), observed at high incidences in rats treated with genotoxic
      carcinogens, was also evident in animals receiving non-genotoxic agents, even
      after their withdrawal, albeit at low incidences. AH labeling indices remained
      high even without continued insult. These results indicate that even with non
      genotoxic carcinogens, heritable alterations at the DNA level could occur during
      strong cell proliferation and result in AH development. This putative
      preneoplastic lesion might then progress to produce carcinomas.

PMID- 8276719
TI  - Enhancement of tumorigenicity and invasion capacity of rat mammary adenocarcinoma
      cells by epidermal growth factor and transforming growth factor-beta.
AB  - We have studied the effects of growth factors and cytokines on the tumorigenicity
      and invasion capacity of tumor cells by using regressor and progressor tumor cell
      lines (ER-1 and ERpP, respectively) derived from an SHR rat mammary
      adenocarcinoma. ER-1 cells regress spontaneously whereas ERpP cells show invasive
      growth and high metastasis to lung and other organs in syngeneic SHR rats. When
      ER-1 cells were pretreated with either epidermal growth factor (EGF) or
      transforming growth factor-beta (TGF-beta) for 24 h in vitro, and
      intraperitoneally transplanted into SHR rats, they grew and killed the host,
      whereas ER-1 cells pretreated with tumor necrosis factor-alpha did not.
      Tumorigenicity and invasion capacity of ERpP cells were also enhanced by
      treatment with EGF and TGF-beta. The ER-1 cells pretreated with EGF, once grown
      in vivo, had acquired irreversible tumorigenicity and invasion capacity without
      requiring further EGF treatment, and the enhanced malignancy was irreversible.
      These findings suggest that growth factors play an important role in acquisition
      of malignancy of tumor cells.

PMID- 8276720
TI  - Immunohistochemical detection of hepatocyte growth factor/scatter factor in human
      cancerous and inflammatory lesions of various organs.
AB  - Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor
      considered to be potentially involved in tissue regeneration, wound healing,
      embryogenesis, angiogenesis and cancer invasion. Here we examined
      immunohistochemically the distribution of HGF/SF in human tissues, including
      cancerous and inflammatory tissues, using anti-HGF antibody. HGF/SF accumulation
      was clearly detected in the extracellular matrix, particularly along the basement
      membrane, in cancerous and inflammatory tissues, but only a little was detected
      in normal tissues. HGF/SF is well known to have a strong affinity for heparin in
      vitro, and from the results of our immunohistochemical assay, we considered that
      HGF/SF was bound to heparin or heparan sulfate of the extracellular matrix and
      basement membrane. HGF/SF was well localized in cancerous and inflammatory
      lesions of human lung, liver and pancreas, and in apparently normal tissues of
      kidney, adrenal gland and pancreas obtained at autopsy. In lung, HGF/SF was
      localized along the basement membranes of cancer cell nests, in the extracellular
      matrix of the cancer cell surface, cancer stroma and tissues invaded by cancer,
      and the basement membranes of bronchial epithelium and capillary vessels in
      inflammatory stroma. Since HGF/SF makes some cancer cells more invasive in vitro,
      the accumulation of HGF/SF in cancerous tissue suggests that the invasiveness of
      some cancer cells may be increased by HGF/SF in vivo.

PMID- 8276721
TI  - Membrane-associated lymphotoxin expression and functional analysis of lymphokine
      activated killer cells derived from tumor-infiltrating lymphocytes.
AB  - The expression of a membrane-associated lymphotoxin molecule (mLT) on lymphokine
      activated killer (LAK) cells obtained from 18 patients with malignant tumors and
      its role in the tumor cell killing mechanisms were investigated. LAK cells from
      tumor-infiltrating lymphocytes (TIL-LAK cells) were mainly composed of CD3
      positive cells, whereas LAK cells from peripheral blood lymphocytes (PBL-LAK
      cells) were mainly composed of CD16- and CD56-positive cells. However, mLT was
      found to be expressed on TIL-LAK cells as well as PBL-LAK cells. The degree of
      mLT expression correlated with the killing activity of LAK cells towards L929
      cells (r = 0.806, P < 0.01, n = 15), but not with that towards Daudi or K562
      cells. Although the degree of mLT expression correlated with the amount of
      secreted lymphotoxin (LT) in the supernatant of LAK cell culture, the secreted LT
      itself could not account for the tumor cell killing activity of LAK cells.
      Polyclonal rabbit anti-LT antibody partially inhibited the killing activities of
      LAK cells towards L929 cells and this inhibition was found in the combination of
      autologous tumor cells and PBL-LAK cells. These findings suggest the possibility
      that the mLT-related cytotoxicity is involved in the tumor cell killing
      mechanisms of TIL-LAK cells as well as PBL-LAK cells.

PMID- 8276722
TI  - Leukemic cell lysis by activated human macrophages: significance of membrane
      associated tumor necrosis factor.
AB  - In this study, we analyzed the mechanism(s) of leukemic cell lysis by human
      macrophages. Peripheral blood monocyte-derived macrophages were activated with
      recombinant interferon-gamma and lipopolysaccharide and their lytic activity
      against two leukemic cell lines (K562 and HL-60 cells) was assessed by an 111In
      releasing assay. Activated macrophages lysed these leukemic cells, and the lytic
      activity against leukemic cells was almost completely inhibited by anti-tumor
      necrosis factor (TNF) antibody. The macrophage-lysate prepared from activated
      macrophages also exhibited significant lytic activity against leukemic cells;
      this lytic activity was inhibited by anti-TNF antibody. The leukemic cells that
      we used for the cytotoxicity assays were resistant to recombinant TNF. The
      culture supernatant of activated macrophages did not show any lytic activity.
      These findings suggest that cell-associated TNF plays a role in macrophage
      mediated cytotoxicity against leukemic cells.

PMID- 8276723
TI  - Production, binding and cytotoxicity of human/mouse chimeric monoclonal antibody
      neocarzinostatin conjugate.
AB  - A human/mouse chimeric Fab monoclonal antibody A7 (chFabA7) was covalently
      coupled to neocarzinostatin (NCS) by the SPDP method at various chFabA7:NCS
      substitution ratios. The antigen-binding activity of the conjugate, examined by
      ELISA using fixed antigen-positive colon cancer cells, was identical to that of
      the parent chFabA7 when one mole of NCS was conjugated, but was reduced with 2 or
      3 moles of conjugated NCS. By means of a colony-forming assay, the cytocidal
      effect of the conjugate on antigen-positive cancer cells was found to be stronger
      than that of free NCS, whereas in antigen-negative cancer cells it was similar to
      that of free NCS. This effect was attenuated by adding an excess amount of
      monoclonal antibody A7. These findings indicate that the conjugate has an antigen
      specific cytocidal action, and thus chFabA7-NCS is a promising tool for targeting
      cancer chemotherapy.

PMID- 8276724
TI  - Chemical modification by polyethylene glycol of the anti-tumor enzyme arginine
      deiminase from Mycoplasma arginini.
AB  - Amino acid-degrading enzymes are known to inhibit the growth of tumor cells in
      culture by depleting amino acids in the medium. Here we demonstrate that arginine
      deiminase (EC 3.5.3.6) from Mycoplasma arginini had stronger growth-inhibitory
      activity against all 4 kinds of tumor cell lines tested than L-asparaginase and
      arginase, which are well-known anti-tumor enzymes. Next, chemical modification of
      the arginine deiminase molecule with polyethylene glycol was shown to enhance its
      potency as an anti-tumor enzyme. The percentage of modified amino groups per
      molecule was estimated to be 51% of the total amino groups, and the average
      molecular weight was estimated to be about 400,000 by gel-filtration HPLC. The
      enzymic activity of the modified enzyme was 25.5 units/mg protein, which was
      equivalent to 57% of that of the native enzyme. The modified enzyme strongly
      inhibited growth of a mouse hepatoma cell line, MH134, at a concentration of more
      than 10 ng/ml, showing almost the same dose-response curve as the native enzyme.
      When a bolus of 5 units of the modified enzyme was intravenously injected into
      male BDF1 mice, L-arginine in the blood completely disappeared within 5 min, and
      remained undetectable for more than 8 days. On the other hand, in the case of
      bolus injection of the same number of units of native enzyme, the plasma L
      arginine level recovered up to 66% of the control level at 8 days. These results
      suggest that this modified enzyme has a longer plasma clearance time and may be
      more effective as a new anti-tumor agent than the native enzyme.

PMID- 8276725
TI  - Photodynamic therapy for cancers: a clinical trial of porfimer sodium in Japan.
AB  - Photodynamic therapy utilizing Photofrin has proven to be an effective modality
      that can be used in the treatment of a wide variety of solid tumors and luminal
      cancers. An argon pumped dye laser or excimer dye laser was used to deliver 630
      nm light via quartz fibers passed through the biopsy channel subsequent to i.v.
      injection of photosensitizer. In this study, 64 patients with superficial cancers
      were treated in this manner but only 58 patients, including 21 with
      roentgenographically occult lung cancer, 8 with stage I lung cancer, 5 with
      esophageal cancer, 12 with gastric cancer, 8 with cervical cancer and 4 with
      bladder cancer were evaluable. Complete remission was obtained in 48 out of 58
      cases (82.8%). There was no serious complication except skin photosensitivity,
      which was seen in 13 patients. We conclude that photodynamic therapy is
      efficacious in the treatment of superficial cancers where complete remission may
      be achieved.

PMID- 8276726
TI  - The effect of a taurine modified diet on normal and hydropic ears of the guinea
      pig.
AB  - Taurine is recognised as the major osmoregulating amino acid in the brain as well
      as other organs. Its possible influence on normal cochlear function and on
      hydropic cochleas of the guinea pig was investigated here. Normally hearing adult
      guinea pigs were placed on either a taurine-depleting diet (B-alanine) or a
      taurine-supplemented diet. At the end of 6 weeks the compound action potential
      audiograms (CAP) in the two groups were similar and appeared not to be different
      from a third control group receiving a non modified diet which suggested that a
      taurine-modified diet had not affected normal cochlear function. In hydropic ears
      the taurine-depleting diet was observed, in some cases, to moderately slow down
      the early phase of the characteristic progression of the CAP sensitivity loss.
      These data are in favor of a homeostatic role for taurine in the inner ear of the
      guinea pig under particular conditions such as osmoregulatory stress.

PMID- 8276727
TI  - Temporal patterns of transient-evoked otoacoustic emissions in normal and
      impaired cochleae.
AB  - The spatial distribution of outer hair cells that participate in generating
      transient-EOE frequency-components has been investigated in man. According to
      several models (e.g. Wilson (1990) Hear. Res. 2, 527-532; Zwicker (1986) J.
      Acoust. Soc. Am. 80, 154-162; Wilson and Kemp (Eds.), Cochlear Mechanisms,
      Structures, Functions and Models, Plenum Press, NY), EOEs result from
      interferences between broadly distributed contributions, responsible for their
      long frequency-dependent delay. This work presents an analysis of the temporal
      patterns of click- and tone-burst-EOEs in human ears when contributions to EOEs
      are reduced by noise-induced lesions with audiometric notches centred around 4
      kHz (N = 46). Although the auditory thresholds at the frequencies of the studied
      EOE-components were always normal, these components exhibited drastic and
      predictable changes compared to normal control ears (N = 40). (1) Their temporal
      pattern at the highest EOE frequency fmax just below the audiometric notch
      appeared to be determined by the cochlear state at high frequencies (6 to 8 kHz).
      Either it was normal and the EOE exhibited a complicated beat-structure, or it
      was impaired and the time envelope of the EOE was simple. In contrast, any type
      of time pattern could be observed in normal ears. (2) The temporal patterns of
      EOEs one octave below fmax always presented many beats and short delays. The
      proposed interpretation is that contributions to a transient-EOE component at
      frequency f can come from distant basal cochlear areas, i.e. more than 1 and
      sometimes 1.5 octaves from the place tuned to f. Therefore, the possible
      relationships between transient-EOEs and tuning mechanisms which presumably
      involve only a small number of OHC need further investigations.

PMID- 8276728
TI  - Acoustic enhancement of electrically-evoked otoacoustic emissions reflects
      basilar membrane tuning: experiment results.
AB  - Acoustic enhancement of the electrically-evoked otoacoustic emissions (EEOEs) was
      investigated by systematically varying acoustic frequency and intensity. The
      results demonstrated that simultaneous acoustic stimulation at frequencies around
      the characteristic frequency of the electrical current injection place was most
      effective in enhancing low-frequency EEOEs. Moreover, it was demonstrated that
      the enhancement was tuned and graded. The enhancement threshold tuning curves
      (defined as sound pressure level needed to achieve 1 dB of enhancement) resembled
      basilar membrane tuning at high sound pressure levels. The data suggest that the
      emissions were generated from a cochlear region near the electrode place, and the
      magnitude of the enhancement depends on the magnitude of the basilar membrane
      response to the acoustic stimulus.

PMID- 8276729
TI  - Aging and otitis media as sources of variance in the rat auditory brainstem
      response.
AB  - Auditory brainstem response (ABR) latencies were examined in normal female
      Sprague-Dawley rats at 6 months of age and in 10-12 month old animals which
      tested positive for Mycoplasma pulmonis, a frequently implicated pathogen in
      otitis media. Significant differences in the peak latencies of Waves I, II and
      IIIn were found between the two age groups. A significant age by intensity
      interaction effect was also identified for Waves II and IIIn. Since the age
      related effects observed in Wave I were similarly reflected in Waves II and IIIn,
      it was concluded that the group differences were due to alterations of the
      auditory periphery and not to changes in the central auditory system.

PMID- 8276730
TI  - Rapid resting ion fluxes in goldfish hair cells are balanced by (Na+,K+)-ATPase.
AB  - Inhibition of sodium/potassium pumping by isolated goldfish hair cells led to a
      rapid gain of sodium and loss of potassium. Half-times for turnover were about 10
      min, among the fastest of any cell type examined by electron-probe analysis.
      Pumping was inhibited by removal of extracellular potassium or by treatment with
      1 mM ouabain, as expected of a classical (Na+,K+)-ATPase. The initial rate of
      entry of sodium after inhibition, about 4 mM/min, provided an estimate of resting
      sodium-entry and sodium-pumping rates. After return to control medium, cells
      loaded with sodium by removal of extracellular potassium could recover their
      normal high-potassium/low-sodium status. The initial rate of recovery (an
      estimate of the cells' maximum sodium-pumping rate) was sufficient to lower cell
      sodium by 10 mM/min. This functional estimate of hair-cell (Na+,K+)-ATPase
      activity was of the same order of magnitude as the biochemical activity of
      (Na+,K+)-ATPase previously reported for sensory epithelia of other species. The
      balance between sodium entry and sodium pumping determines hair-cell ionic
      composition, and thus the resting potential and the driving forces for sodium
      coupled transport processes. Imbalance due to excess sodium entry or loss of pump
      capacity could have significant consequences for hair-cell function and
      integrity.

PMID- 8276731
TI  - Statistical quantification of 24-hour and monthly variabilities of spontaneous
      otoacoustic emission frequency in humans.
AB  - Previous evidence has suggested a relationship between spontaneous otoacoustic
      emissions (SOAEs) and established, biological cycles, although detailed
      statistical quantifications of the suggested relationships do not exist in the
      literature. In an attempt to statistically quantify the purported circadian and
      monthly influences on this phenomenon, two experiments were undertaken. The first
      experiment was conducted over eight weeks, investigating 31 SOAEs recorded from
      eight women and two men. Time series statistical analysis examined whether daily,
      weekly, and/or monthly cycles characterized SOAE frequency variability. Results
      yielded a significant monthly cycle for the majority of SOAEs recorded from the
      women but for none of the SOAEs recorded from the men. These results suggest the
      possibility that SOAE frequency fluctuation in women may be entrained to the
      monthly menstrual cycle. In the second experiment, hourly SOAE frequency
      stability was examined over a 24-h period to ascertain the nature of the daily
      frequency variation as precisely as possible. Four SOAEs from two subjects were
      examined, and time series analysis of these data included (1) modelling the
      autocorrelation structure of the measurements, (2) resolving each 24-h series of
      measurements into cyclical components of various periodicities, and (3) testing
      the statistical significance of given cycles within the spectrum of each series.
      Findings included a significant 24-h variability of frequency for each SOAE,
      suggesting the possibility of a circadian influence on frequency fluctuation.
      Results from the two experiments provide quantitative evidence supporting a
      hypothetical relationship between SOAEs and established, biological cycles.

PMID- 8276732
TI  - Distortion-product emissions in rabbit: I. Altered susceptibility to repeated
      pure-tone exposures.
AB  - An important issue in understanding the development of noise-induced hearing loss
      is whether prior acoustic overstimulation alters the susceptibility of the
      cochlea to further damage. The present work was designed to establish a model of
      activity-dependent changes in the susceptibility of the cochlea to acoustic
      overstimulation by regularly exposing the ear to a low-frequency pure tone. As a
      quantitative index of cochlear function, 2f1-f2 distortion-product otoacoustic
      emissions (DPOAEs) were monitored systematically over time in three groups of
      rabbits, with each group experiencing a unique paradigm that incorporated
      repeated exposure to the low-frequency tone. Common to each rabbit's exposure
      protocol was that a given experimental session consisted of two exposure
      episodes, separated by a 40-min period. Experimental sessions were repeated three
      times, with 2- to 3-day recovery periods interposed between sessions. The rate of
      decrement in DPOAE amplitude over a prescribed time period was utilized as a
      measure of susceptibility to the acoustic trauma. The overall results indicated
      that ears were more susceptible to exposure 40 mins after the first exposure of a
      session than they were initially. A series of control experiments indicated that
      the robustness of the acoustic middle-ear reflex (AMR) did not change between the
      exposure episodes. Consequently, changes in the AMR could not account for the
      increased susceptibility seen following the first exposure. However, in awake
      rabbits with stronger AMRs, higher pure-tone exposure levels were needed to
      produce increased susceptibility to the second exposure. After 2-3 days of
      intersession recovery, susceptibility to the effects of excessive sound returned
      close to its original baseline level. The outcome of these studies demonstrated a
      reduced capacity for the ear to resist the harmful effects of exposure to a
      moderately intense tone, which was repeated twice over a brief 40-min period, but
      little change in susceptibility when identical exposures were repeated over
      longer intersession intervals of several days.

PMID- 8276733
TI  - Distortion-product emissions in rabbit: II. Prediction of chronic-noise effects
      by brief pure-tone exposures.
AB  - In an attempt to predict the susceptibility of the cochlea to the harmful
      influences of excessive sound, the effects of initially exposing the same rabbits
      to brief pure-tones were related to the subsequent effects of octave-band noise
      (OBN) exposure using measures of distortion-product otoacoustic emissions
      (DPOAEs). The pure-tone exposure paradigm consisted of determining the rate at
      which a 100-dB SPL, low-frequency tone reduced the amplitude of a 1.5-kHz DPOAE,
      elicited by 50-dB SPL primaries. To establish the stability of the rate-reduction
      index, the tonal-exposure protocol was repeated on three separate occasions for
      each subject. Subsequently, the same rabbits were exposed chronically to a 95-dB
      SPL OBN, centered at 1-kHz, until DPOAE amplitudes between 1-5 kHz were
      diminished to noise-floor levels, i.e., by 10-30 dB, in response to 45-dB SPL
      primaries. The results revealed a visually apparent relation between the slope of
      the tonal-induced DPOAE-loss functions and the number of days required to reach
      the criterion decrement in emission level during chronic exposure to noise.
      Analysis of the frequency extent of the noise-induced changes revealed
      significant correlations between the previously measured rate of pure-tone
      induced reductions of DPOAE amplitude and the subsequent amount of decrement
      produced by OBN exposure. Thus, rabbits exhibiting slow rates of tonal-induced
      decrements in low-frequency DPOAEs were resistant to the amplitude-reducing
      effects of a subsequent chronic OBN exposure in that it typically took more than
      four days to achieve the targeted amount of DPOAE loss.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8276734
TI  - Evidence for calcium-binding proteins and calcium-dependent regulatory proteins
      in sensory cells of the organ of Corti.
AB  - Calcium is thought to play a major signaling role in outer hair cells to control
      metabolism, cytoskeletal integrity, cell shape and cell excitability. For this to
      happen, in resting cells the concentration of free calcium ions must be
      maintained at low levels so that focal increases can trigger specific events. In
      this paper, the localization of calcium, calcium-binding and calcium-dependent
      regulatory proteins in sensory cells from the guinea pig inner ear was
      demonstrated using immunocytochemical and histochemical techniques. We found the
      calcium buffer and/or calcium sensor proteins calmodulin, calbindin and
      calsequestrin predominantly in sensory cells and that when present, these
      proteins can be enriched in the outer hair cells. Calmodulin is found in the
      stereocilia, in the cuticular plate and in the cytoplasm and calbindin is found
      only in the cuticular plate and cytoplasm of both the inner and outer hair cells.
      The staining for these proteins in the outer hair cells is homogeneous, with no
      apparent compartmentalization along the lateral wall. Calsequestrin, thought to
      store and release calcium from membrane bound intracellular storage sites is
      found only in the cytoplasm of outer hair cells. There, it has a more punctuate
      staining pattern than does calmodulin or calbindin suggesting that it may be
      present in calciosomes rather than soluble in the cytoplasm. We did not detect
      caldesmon and S-100. Using the potassium pyroantimonate technique, we found
      precipitates containing calcium ions distributed throughout the cytoplasm of
      outer hair cells, with no evidence that the subsurface cisterns along the lateral
      wall act as calcium storage sites. Thus, calcium in resting cells is found in the
      cytoplasm along with calbindin and calmodulin and appears to have a punctate
      distribution consistent with a co-localization with calsequestrin. The
      implications of this distribution with respect to the slow shortening and
      elongation seen in outer hair cells are discussed.

PMID- 8276735
TI  - Hair-cell regeneration in organ cultures of the postnatal chicken inner ear.
AB  - The sensory epithelium of the avian inner ear retains into adulthood progenitor
      cells for inner-ear hair cells and other cell types in the epithelium. Hair cells
      are produced normally on an ongoing basis in the vestibular sensory epithelium,
      and hair-cell production is increased after insult in both auditory and
      vestibular sensory epithelia. The details of postnatal hair-cell production are
      not understood. In particular, molecular factors involved in the initiation and
      regulation of hair-cell genesis and differentiation are not known. Studies of
      this phenomena have been hampered by the lack of cell culture models. An organ
      culture system was developed which encourages generation and differentiation of
      hair cells in mature inner-ear sensory epithelia. Continuous labeling with
      tritiated thymidine showed genesis of both supporting cells and hair cells in
      normal vestibular epithelia grown in culture, and an increase in hair-cell and
      supporting-cell proliferation in damaged sensory epithelia grown in culture as
      compared to undamaged controls. This demonstrates, in vitro, both the division
      and differentiation of hair-cell progenitor cells in normal vestibular epithelia,
      and the maintenance of the hair-cell regeneration process in damaged inner-ear
      epithelia. This culture system should be useful for studies of hair-cell genesis
      and differentiation as well as studies of hair-cell and supporting-cell
      functioning in general.

PMID- 8276736
TI  - Improvement in fluoxetine-associated sexual dysfunction in patients switched to
      bupropion.
AB  - BACKGROUND: This study was conducted to determine the effect of bupropion on the
      sexual functioning of male and female outpatients who developed anorgasmia or
      delayed orgasm while receiving fluoxetine treatment for depression. METHOD:
      Thirty-nine patients who satisfied criteria for participation in the study
      discontinued fluoxetine treatment and entered a 2-week washout phase followed by
      an open 8-week bupropion treatment phase. Three parameters of sexual functioning
      were followed throughout the study: orgasm function, libido, and satisfaction
      with overall sexual functioning. Depression was also evaluated at each visit.
      RESULTS: All patients reported orgasm delay and/or failure at the time of
      fluoxetine discontinuation. Orgasm function, libido, and satisfaction with sexual
      functioning improved during the 2-week fluoxetine washout period and during the
      bupropion treatment phase. Ninety-four percent of patients (29/31) had complete
      or partial resolution of their orgasm dysfunction at the end of bupropion
      treatment, and 81% of patients (25/31) were "much" or "very much" more satisfied
      with their overall sexual functioning. Most patients entered the study with
      decreased libido on fluoxetine. Libido was "much" or "very much" increased for
      81% of patients (25/31) at the end of the study. In addition, depression scores
      on the Hamilton Rating Scale for Depression and Clinical Global Impressions
      Severity scale significantly improved during the bupropion treatment phase.
      Finally, bupropion was well tolerated by most patients. CONCLUSION: Bupropion may
      be an appropriate antidepressant for patients who develop sexual dysfunction
      during fluoxetine treatment or for whom sexual dysfunction is a concern.

PMID- 8276737
TI  - High risk of eosinophilia in women treated with clozapine.
AB  - BACKGROUND: Eosinophilia associated with clozapine treatment has been reported in
      some studies and limited case reports. Because little is known regarding
      incidence, course, and relevance of this finding, clozapine therapy has been
      terminated prematurely in some patients with elevated eosinophil counts. METHOD:
      Records were reviewed on 118 consecutively hospitalized, acutely psychotic
      patients treated over a 1-year period with clozapine for at least 3 weeks.
      Demographic data were obtained on those patients, and white blood cell counts
      were analyzed. We reviewed the data for predisposing factors, associated medical
      findings, or clinical sequelae, and performed a two-sided Fisher's exact test to
      determine if sex or diagnosis was associated with a higher risk of developing
      eosinophilia. The literature pertaining to this blood dyscrasia and its
      relationship to clozapine was reviewed. RESULTS: In our population, the
      cumulative incidence of eosinophilia among women was 23% (13/57), a statistically
      significant higher risk (p < .01) than that in men (7% [4/61]). In all cases, the
      eosinophilia was noted between Weeks 3 and 5 of treatment and resolved without
      medical or psychiatric complications. CONCLUSION: Eosinophilia should be added to
      the list of commonly observed side effects of clozapine treatment. Women appear
      to be at significant risk. Eosinophilia usually occurs early in therapy,
      spontaneously resolves, and is not associated with any known complications. An
      otherwise healthy person with this blood dyscrasia may continue with treatment
      but should be monitored closely. Further investigation into this finding may
      provide insight into the mechanism of neutropenia and other adverse reactions to
      clozapine.

PMID- 8276738
TI  - Postpartum onset of panic disorder: a coincidental event?
AB  - BACKGROUND: This study investigated whether the onset of panic for the first time
      during the postpartum period represented a coincidental occurrence. METHOD: Sixty
      four childbearing women diagnosed with panic disorder who had been treated at the
      Yale Anxiety Research Clinic were interviewed. Postpartum panic was defined as
      the first panic occurring within 12 weeks of the woman's first childbirth.
      RESULTS: Seven women (10.9%) met criteria for postpartum onset, which is
      significantly greater than the expected age-corrected percentage of 0.92%, Z =
      2.29, p < .02. CONCLUSION: The onset of panic in the first postpartum period is
      not a coincidental event.

PMID- 8276740
TI  - Combined carbamazepine-buspirone treatment of alcohol dependence.

PMID- 8276739
TI  - Clomipramine in the treatment of agoraphobic inpatients resistant to behavioral
      therapy.
AB  - BACKGROUND: Both behavior-modification methods and antidepressants have proved to
      be effective in the treatment of agoraphobia. The authors examined the effects of
      clomipramine on agoraphobia in patients who failed to respond to exposure-based
      behavioral treatment. METHOD: Eighteen patients with panic disorder with
      agoraphobia who had not responded to previous inpatient behavioral treatment were
      recruited to a 12-week, placebo-controlled, double-blind crossover study of
      clomipramine, at top doses of 150 mg/day for 3 weeks. The patients were assessed
      on measures of phobic avoidance, agoraphobic cognitions, panic, state and trait
      anxiety, subjective anxiety, and depression. RESULTS: One patient dropped out of
      the study after 6 weeks. On most outcome measures, the 17 study completers had
      significantly (p < .05) lower symptom scores at posttest in the active drug
      period than at posttest in the placebo period; however, the clinical gains were
      modest. CONCLUSION: The short-term efficacy of clomipramine for agoraphobic
      patients who failed to respond lastingly to behavioral treatment was
      demonstrated. It remains to be shown that clomipramine can lead to clinically
      significant and lasting benefits in these patients.

PMID- 8276741
TI  - Panic-like symptoms after veralipride withdrawal.

PMID- 8276742
TI  - Acute delirium and parkinsonism in a bupropion-treated liver transplant
      recipient.

PMID- 8276743
TI  - Fregoli syndrome with a jealous theme.

PMID- 8276744
TI  - Heritability of social anxiety: a brief review.
AB  - Although recent advances have greatly improved the treatment of and prognosis for
      social phobia, its etiology remains relatively unexplored. One promising area of
      investigation is the role of intergenerational transmission. This paper provides
      an overview of twin and family studies of social anxiety, specifically focusing
      on questions of evidence for heritability, relative contributions of genetic
      versus environmental factors, and the implications of variations in diagnostic
      definitions, e.g., social phobia versus shyness.

PMID- 8276745
TI  - The role of nuclear magnetic resonance imaging in psychiatric research.
AB  - Magnetic resonance imaging (MRI) has become an important tool in the
      investigation of cerebral abnormalities associated with psychiatric illnesses.
      There are a number of benefits of investigating psychiatric illness with MRI,
      which is superior to computed tomography scanning. MRI has been used to study
      neurologic deficits seen in schizophrenia, affective disorders, dementia, and
      more recently, anxiety disorders. Magnetic resonance spectroscopy offers a new
      investigational technique that adds functional information to the structural
      changes seen with standard MRI scanning. This review highlights the current data
      in living human subjects that demonstrate structural changes in psychiatric
      disorders using MRI, including recent studies of the anxiety disorders.

PMID- 8276746
TI  - Magnetic resonance spectroscopy in social phobia: preliminary findings.
AB  - Proton localized magnetic resonance spectroscopy was studied in 20 social phobics
      and 20 age- and sex-matched controls. Stimulated Echo Acquisition Mode volume
      element localization was used with chemical shift imaging. Choline and creatine
      signal-to-noise ratios (SNRs) were significantly lower in social phobia than in
      controls in subcortical, thalamic, and caudate areas. In the social phobic group,
      N-acetylaspartate (NAA) SNR was significantly lower in cortical and subcortical
      regions, and ratios of NAA to other metabolites were lower in social phobia.
      Choline, creatine, and NAA SNRs were inversely correlated to total social phobia
      and fear symptoms, as measured by the Brief Social Phobia Scale, in the thalamic
      and noncortical gray areas. In a small number of patients who received
      clonazepam, posttreatment SNRs generally increased relative to baseline. Our
      results suggest a promising place for magnetic resonance spectroscopy in social
      phobia and also indicate potential pharmacodynamic uses of this technique.

PMID- 8276747
TI  - Neurobiology of social phobia.
AB  - The neurobiology of social phobia has been examined using four research
      strategies employed to investigate the neurobiology of patients with other
      anxiety or mood disorders--chemical challenge paradigms, psychoneuroendocrine
      assessments, naturalistic challenges, and neuropharmacologic challenges. This
      article reviews the studies that used each of the research paradigms in patients
      with social phobia. The author describes these results in the context of the
      results of other anxiety disorder studies using these four strategies and
      discusses implications for future research.

PMID- 8276748
TI  - Pharmacotherapy of social phobia.
AB  - The Liebowitz Social Anxiety Scale (LSAS) was developed to help clinicians
      evaluate data by examining fear and avoidance together in order to provide a
      fuller understanding of anxiety disorders. A number of pharmacologic agents have
      been studied in social phobia, including monoamine oxidase inhibitors, serotonin
      selective reuptake inhibitors, tricyclics, and benzodiazepines. This paper
      reviews the findings of several open and double-blind clinical trials using the
      LSAS and other measures. Promising results have been achieved with some
      pharmacologic agents, although further controlled trials are necessary.

PMID- 8276749
TI  - Specific issues in the cognitive-behavioral treatment of social phobia.
AB  - Cognitive-behavioral approaches to the treatment of social phobia are selectively
      reviewed. The review examines three specific questions of importance in the
      cognitive-behavioral treatment literature: (1) What is the role of cognitive
      techniques in the treatment of social phobia, especially in conjunction with
      behavioral techniques like in vivo exposure or social skills training? (2) Is
      there long-term maintenance of gains as a result of cognitive-behavioral
      treatment of social phobia? (3) How does cognitive-behavioral treatment of social
      phobia compare with pharmacologic treatment approaches? This review presents
      studies that address these questions, offers tentative answers, and outlines
      directions for future research on the cognitive-behavioral treatment of social
      phobia.

PMID- 8276750
TI  - Social phobia: the consumer's perspective.
AB  - Although social phobia is a treatable condition, it remains a stepchild in the
      health care system. Consequently, the majority of sufferers, an estimated 2.4
      million American adults, go untreated. The Anxiety Disorders Association of
      America (ADAA) seeks to lower the barriers to treatment by supporting programs to
      promote awareness of social phobia among the public and health care
      professionals. The small minority of patients who do have access to treatment,
      which generally includes cognitive-behavioral and/or pharmacologic therapy, are
      able to improve their personal and professional lives and return to productive
      and satisfying lifestyles. This article describes the breadth of the problem of
      untreated social phobia, the need for early identification and treatment, and the
      significant improvements in patients' lives that can be achieved with
      professional care.

PMID- 8276751
TI  - Phosphatidylserine specific binding protein in rat brain: purification and
      characterization.
AB  - A calcium-independent phosphatidylserine specific binding protein detected on
      liposome blotting analysis was purified from rat brain and revealed to be
      identical to myristoylated, alanine-rich C kinase substrate (MARCKS). MARCKS
      specifically binds to phosphatidylserine but not phosphatidylcholine. The binding
      of MARCKS to phosphatidylserine was abolished on protein kinase C-dependent
      phosphorylation. Since bacterially expressed MARCKS also specifically binds to
      phosphatidylserine, myristoylation of the N-terminal glycine seems not to be
      essential for the binding of MARCKS to phosphatidylserine. These data suggest
      that phosphatidylserine is a membranous target molecule of MARCKS.

PMID- 8276752
TI  - Characterization of wild type and mutant chicken gizzard alpha calponin expressed
      in E. coli.
AB  - Calponin is a thin filament-associated protein that is implicated in the
      regulation and maintenance of smooth muscle contraction. Molecular cloning of
      chicken gizzard calponin indicated the presence of two isoforms, alpha and beta,
      the expression of the alpha-isoform being uniformly more abundant in various
      smooth muscle tissues [Takahashi, K. & Nadal-Ginard, B. (1991) J. Biol. Chem.
      266, 13284-13288]. For the long-range goal of understanding of the structure and
      function of calponin, we have started bacterial expression and site-directed
      mutagenesis of alpha calponin. The amino acid composition and N-terminal sequence
      of the recombinant alpha calponin were found to be identical to those deduced
      from its nucleotide sequence. Recombinant alpha calponin is capable of binding to
      calmodulin, troponin C, tropomyosin, and actin, and of inhibiting skeletal muscle
      acto-subfragment-1 ATPase activity. A mutant alpha calponin with a replacement in
      the putative inhibitory region (residues 146-171) has impaired ability to inhibit
      the acto-subfragment-1 ATPase activity, suggesting that this region of calponin
      may be involved in the modulation of the actin-myosin interactions.

PMID- 8276754
TI  - A new O-acetylated trisialoganglioside, 9-O-acetyl GT2, in cod brain.
AB  - An O-acetylated trisialoganglioside that is converted to GT2 on mild base
      treatment was found in cod brain. This alkali-labile ganglioside was isolated
      using high-performance liquid chromatography, and its chemical structure was
      characterized. This novel ganglioside was identified as a GT2 derivative having
      an acetyl group at the C-9 position of the external sialic acid. Its chemical
      structure is as follows.

PMID- 8276753
TI  - A new crystal form of proteinase A, a non-pepsin-type acid proteinase from
      Aspergillus niger var. macrosporus.
AB  - Proteinase A from Aspergillus niger var. macrosporus is a non-pepsin-type acid
      proteinase, whose catalytic residues and mechanism remain to be elucidated. A new
      form of proteinase A crystals more suitable for crystallography than that
      obtained previously was prepared from an ammonium sulfate solution at pH 3.5 by
      the hanging-drop vapor diffusion method. The space group of the crystals was
      P2(1)2(1)2(1), with unit cell dimensions of a = 69.75 +/- 0.06 A, b = 87.55 +/-
      0.05 A, and c = 60.83 +/- 0.04 A. On the assumption of two enzyme molecules per
      asymmetric unit, the calculated volume to unit protein mass ratio (Vm) was 2.08
      A3/Da. By assuming the specific volume to be 0.74 cm3/g, the solvent content
      (Vso1) was estimated to be 41%, i.e., much larger than that of the crystal form
      obtained previously at pH 2.0 (Vso1 = 26%). Diffraction data were collected up to
      a resolution higher than 1.6 A, using the Weissenberg camera for macromolecular
      crystallography with synchrotron radiation.

PMID- 8276755
TI  - Effect of high hydrostatic pressure on the conversion of alpha-connectin to beta
      connectin.
AB  - The factors affecting the conversion of alpha-connectin to beta-connectin induced
      by pressurization of muscle were investigated over a pressure range from 100 to
      400 MPa by using SDS-PAGE and immunoblot analysis. When muscles were exposed to
      high pressures, the conversion of alpha-connectin to beta-connectin was the most
      pronounced at a pressure of 300 MPa, and the appearance of 1,200-kDa peptide
      accompanied by conversion of alpha- to beta-connectin was observed. Connectin was
      relatively resistant to degradation under a pressure of 400 MPa. The degradative
      products of beta-connectin reactive with mAb 2D4 were not observed. The effect of
      high pressure on connectin in isolated myofibrils was similar to that on
      connectin in muscle. Addition of leupeptin and E-64 to the isolated myofibrils
      resulted in the prevention of the degradation of connectin at each stage of the
      pressurization. The ability of calcium-activated protease (calpain) to hydrolyze
      connectin from alpha to beta gradually declined with increasing pressure. The
      results indicate that calpain is responsible for the pressure-induced conversion
      of alpha- to beta-connectin. The rate of this conversion is probably regulated by
      the pressure-dependent structural change of alpha-connectin and inactivation of
      calpain.

PMID- 8276756
TI  - Determination of carboxyl-terminal residue and disulfide bonds of MACIF (CD59), a
      glycosyl-phosphatidylinositol-anchored membrane protein.
AB  - MACIF (CD59) is a glycosyl-phosphatidylinositol (GPI)-anchored membrane
      glycoprotein which inhibits the formation of membrane attack complex of human
      complement. MACIF prepared from human erythrocyte membranes was digested with
      pronase. When the digest was subjected to two-phase partition with butanol and
      0.1 N HCl, the carboxyl-terminal peptide was recovered in the butanol phase
      because of the attachment of the highly hydrophobic GPI. The amino acid sequence
      of the peptide was determined to be Asn72 at its amino-terminus and up to Glu76,
      while the presence of Asn77 was ambiguous. To allow unequivocal determination of
      the carboxyl-terminus, a soluble form of MACIF was prepared from human urine on a
      large scale. The carboxyl-terminal peptide from the soluble form was prepared by
      tryptic digestion followed by reversed-phase HPLC. The sequence and composition
      of the peptide unequivocally revealed Asn77 as the carboxyl-terminus. The pattern
      of disulfide bonds of MACIF was also determined with the membrane form as well as
      the soluble form. Cystine-containing peptides were prepared by chymotryptic and
      tryptic digestion, purified by HPLC, and their amino acid sequences were
      determined. The results indicated that disulfide bonds were formed at Cys3-Cys26,
      Cys6-Cys13, Cys19-Cys39, Cys45-Cys63 (or 64), and Cys63 (or 64)-Cys69.

PMID- 8276757
TI  - Effects of novel polyamines on cell-free polypeptide synthesis catalyzed by
      Thermus thermophilus HB8 extract.
AB  - Effects of novel, naturally occurring polyamines on protein synthesis catalyzed
      by Thermus thermophilus cell-free extract were investigated. The results revealed
      the physiological importance of a branched quaternary polyamine, tetrakis(3
      aminopropyl) ammonium, in thermophile protein biosynthesis. Longer polyamines
      than triamine supported the polypeptide synthesis at high temperature, though
      both the activity and the optimum temperature varied depending on polyamines
      added. The highest activity was found when tetrakis(3-aminopropyl)ammonium and a
      tetraamine were simultaneously present. The optimum temperature of the reaction
      supported by the combination of the branched polyamine and spermine was the
      highest and in accord with the optimum temperature of the bacterial growth. These
      results suggested an essential role of the quaternary amine in protein synthesis
      in vivo. This amine effectively stabilized the ternary complex between ribosomes,
      the messenger, and phenylalanyl-tRNA, and this stabilization may account, at
      least in part, for its action on the present reaction. In contrast, another
      branched polyamine, tris(3-aminopropyl)amine supported the activity only
      moderately even in the presence of another polyamine, though the tris amine
      stabilized the ternary complex as effectively as the quaternary amine. This
      result suggests the presence of another essential site for polyamine action in
      the thermophile polypeptide synthesis, in addition to the stabilization of the
      ternary complex. The effects of polyamines on MS2 RNA directed reaction resembled
      those on poly(U) directed polypeptide synthesis, indicating that polyamines are
      essential in protein biosynthesis directed by natural messengers in vivo. The
      quaternary amine inhibited the aminoacylation of tRNA(Phe), and the inhibition
      was canceled by the addition of another polyamine.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8276758
TI  - 1-Alkyl-2,3-diacylglycerol synthesis in primary culture cells of guinea pig
      harderian gland.
AB  - Using a primary culture system of guinea pig Harderian gland cells, we
      investigated the metabolism of a unique lipid: 1-alkyl-2,3-diacylglycerol
      containing methyl-branched fatty acids. The cells were obtained by collagenase
      digestion, and cells with lipid-droplets were collected by two-step
      centrifugation. We cultured these cells, and examined their lipid and fatty acid
      compositions. The de novo synthesis of lipids in these cells was studied as to
      the incorporation of [1(2)-14C]acetate and [U-14C]glucose. The major lipid proved
      to be 1-alkyl-2,3-diacylglycerol, as in tissue, and it contained a large amount
      of methylbranched fatty acids specific to this gland. The incorporation of
      [14C]acetate and [14C]glucose into 1-alkyl-2,3-diacylglycerol in the cultured
      cells amounted to 79.7 and 88.2% of the total incorporation into the lipid
      fraction, respectively. The incorporation of [14C]acetate into fatty acids in the
      cultured cells was detected for the chain lengths of C14 to C25. The activities
      of glycerol-3-phosphate dehydrogenase in the cultured cells and Harderian gland
      were lower than that in adipose tissue. These results confirm that cultured cells
      reflect the lipid metabolism originating in the Harderian gland and show that
      this culture system can serve as one part of the armamentarium for further study
      of this unique lipid metabolism.

PMID- 8276759
TI  - Interaction of vinculin with the clathrin heavy chain.
AB  - To further document the interaction of vinculin with the clathrin heavy chain
      (CHC) which was observed by using gel overlay, co-sedimentation experiments were
      performed and attempts were made to localize the domains involved on both
      molecules. The binding properties of proteolytic fragments of vinculin were
      investigated after cleavage with V8 protease. Neither the isolated globular
      domain, nor the C-terminal rod domain were able to interact with the CHC. Either
      the interaction involved the portion of vinculin which links these two domains,
      or the region of vinculin mediating the interaction was present on one of the two
      major fragments, but the cleavage itself resulted in conformational changes which
      abolished the binding. The first hypothesis could be ruled out using alpha
      chymotrypsin generated fragments of vinculin, suggesting that the native
      conformation of vinculin might play an important role. Proteolytic cleavage of
      CHC with trypsin demonstrated that the interaction with vinculin is mediated by
      the proximal or distal segment of the CHC. Presence of clathrin light chain (CLC)
      associated with the CHC did not affect its interaction with vinculin. Vinculin
      did not interact with the CLC.

PMID- 8276760
TI  - Novel oligosaccharides with the sialyl-Le(a) structure in human milk.
AB  - Two novel oligosaccharides with the sialyl-Le(a) structure were isolated from
      human milk using a monoclonal antibody, MSW 113. These oligosaccharides were
      purified by affinity chromatography on a column of the immobilized monoclonal
      antibody and by high-performance liquid chromatography, and structurally
      characterized by a combination of 600-MHz 1H NMR spectroscopy and fast atom
      bombardment mass spectrometry. The structural studies indicated the structures of
      these oligosaccharides to be: [formula: see text]

PMID- 8276761
TI  - Dynamics and participation of type II phospholipase A2 in rat zymosan-induced
      pleurisy.
AB  - Intrapleural injection of zymosan into rats induces acute inflammation
      characterized by plasma leakage and cellular influx. The level of type II
      phospholipase A2 (PLA2) increased in the pleural fluid as well as in exudating
      leukocytes after the injection of zymosan. Rather low PLA2 activity was found in
      cell lysates, though treatment of such lysates at low pH increased the PLA2
      activity drastically. The appearance of "acid-extracted" PLA2 activity in
      leukocytes preceded that of the extracellular enzyme activity, suggesting that
      pleural leukocytes might be one of the origins of the extracellular enzyme.
      Treatment of exudating pleural leukocytes with purified rat type II PLA2 elicited
      the production of prostaglandin E2, but not platelet-activating factor
      appreciably. These findings indicate that type II PLA2 might play a role in the
      progression of inflammation through the production of eicosanoids in the present
      inflammation model.

PMID- 8276762
TI  - Effect of single base substitutions at glycine-870 codon of gramicidin S
      synthetase 2 gene on proline activation.
AB  - The mutant gene coding for a proline-activating domain (grs2-pro) was cloned and
      sequenced from Bacillus brevis Nagano, BII-3 strain, which produces gramicidin S
      synthetase 2 defective in proline-activation. By comparison of the nucleotide
      sequence with the wild-type sequence, a single point mutation was found at the
      2609th guanine, which was replaced with adenine, resulting in the change of the
      870th glycine to glutamic acid. Homology search for the deduced amino acid
      sequence of grs2-pro gene revealed that the 870th glycine was conserved in
      adenylate-forming enzymes, and its flanking sequence was highly conserved among
      the aminoacyl adenylate-forming enzymes, such as antibiotic peptide synthetases:
      gramicidin S synthetase 1 and 2 (GS1, GS2), tyrocidine synthetase 1 (TS1), and
      delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS); and other
      aminoacyl adenylation enzymes: alpha-aminoadipate reductase (LYS2), EntF, and
      AngR. On the other hand, this flanking sequence was not conserved in the other
      adenylate-forming enzymes lacking amino acid activation, such as acetyl-CoA
      synthetase, long-chain acyl-CoA synthetase, luciferase, and 4-coumarate CoA
      ligase. Single base substitutions at the 870th GGG codon were carried out by
      oligonucleotide site-directed mutagenesis. Four mutagenized clones were isolated,
      containing grs2-pro genes which exchange 870-Gly for alanine, valine, arginine,
      and tryptophan. The translated products from these clones could scarcely catalyze
      proline-dependent ATP-32PPi exchange reaction. The coil structure of 870-Gly
      region was lost in the mutants. These results suggest that the 870-Gly residue of
      grs2-pro protein is essential for aminoacyl-adenylation in the antibiotic peptide
      synthetase family.

PMID- 8276763
TI  - Cloning of the rat aortic smooth muscle Na+/Ca2+ exchanger and tissue-specific
      expression of isoforms.
AB  - The amino acid sequences of two isoforms of the rat aortic smooth muscle Na+/Ca2+
      exchanger have been deduced by cloning and sequencing the cDNAs. These isoforms
      are identical in nucleotide sequence except that one has a 23-amino acid
      insertion at amino acid position 570. They are highly homologous to the canine
      cardiac exchanger except for the NH2-terminal portion and part of the large
      central hydrophilic domain (amino acid residues 570-631). They are 902 and 925
      (with the insertion) amino acid long with calculated molecular masses of 100,676
      and 103,200 (with the insertion), respectively, if the NH2-terminal 32-amino acid
      residues are eliminated as a cleaved signal sequence. Amplification of the
      variable region (amino acids 570-631) of the exchanger by means of the reverse
      transcriptase-polymerase chain reaction and DNA sequencing revealed that many
      isoforms of the exchanger are expressed in different rat tissues. The two clones
      isolated in this study are the predominant isoforms expressed in aorta, stomach,
      liver, and kidney. In cardiac and skeletal muscles, another isoform is dominant,
      which is equivalent to the canine cardiac exchanger. In brain, a third type is
      predominantly expressed. Alignment of the nucleotide sequences of these isoforms
      and Southern blot analysis of rat genomic DNA suggested that each isoform is
      generated through alternative splicing of the primary transcript.

PMID- 8276764
TI  - Recoverin alters its surface properties depending on both calcium-binding and N
      terminal myristoylation.
AB  - The solution structure and calcium-dependent structural changes of recoverin, a
      23 kDa calcium binding protein of vertebrate photoreceptors, have been studied by
      small-angle X-ray scattering and CD, as well as the effect of N-terminal
      myristoylation. The CD spectrum is not affected by N-terminal myristoylation, but
      strongly affected by Ca2+, indicating that N-terminal myristoylation alone does
      not cause a conformational change. The major conformational change in recoverin
      induced by Ca2+ is characterized as a decrease in the alpha-helical content of
      the protein and an increase in global size upon removal of Ca2+. In the presence
      of Ca2+, unmyristoylated recoverin is monomeric and globular in solution, while N
      terminal myristoylation brings about aggregation. In the absence of Ca2+,
      unmyristoylated recoverin tends to aggregate, while myristoylated recoverin
      becomes monomeric and globular. These observations indicate that recoverin
      changes its surface properties depending on both calcium binding and N-terminal
      myristoylation. Melittin interacts non-specifically only with the myristoylated
      recoverin in the absence of Ca2+. This may be indicative of the properties of the
      interaction between recoverin and its normal physiological target enzyme.

PMID- 8276765
TI  - Detection of a novel 9-kDa endoplasmic reticulum membrane protein in mammalian
      cells by chemical cross-linking with translocating nascent peptides.
AB  - It is widely accepted that a proteinous channel participates in the co
      translational translocation of proteins across the endoplasmic reticulum (ER)
      membrane. Truncated mRNAs encoding N-terminal 70, 75, 88, and 110 amino acids of
      interleukin 2 were translated with wheat germ cell-free system in the presence of
      rough microsomal membrane (RM), and integral membrane proteins were probed with
      the translocating nascent peptides by using a cross-linking reagent (DSS). Two
      membrane proteins, 9 kDa (Cp9, cross-linking partner 9 k) and 39 kDa (Cp39, cross
      linking partner 39 k), were cross-linked with the 75 amino acids nascent peptide.
      When NEM-treated RM was used for the translocation reaction, neither Cp9 nor Cp39
      proteins were cross-linked. When the translation products were treated with
      puromycin before the cross-linking, both proteins were not cross-linked. The
      cross-linked products of Cp9 and Cp39 were not extracted by alkaline extraction
      of the membrane, not sensitive to endoglycosidase H, and did not bind to Con A
      Sepharose. These results indicate that both of the cross-linking partners were
      nonglycosylated integral membrane proteins. Cp39 was cross-linked with the 70,
      88, and 110 amino acid nascent peptides as well as the 75 amino acid peptide,
      whereas Cp9 reacted only with the nascent peptides consisting of 70 and 75 amino
      acid residues. Even after the digitonin treatment of the RM with the
      translocating intermediates, the cross-linked products with Cp9 and Cp39 were
      detected. Cp9 and Cp39 seem to be tightly associated with the ribosome-nascent
      peptide complex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276766
TI  - A pseudo-symmetric DNA binding motif of purified Rep dimer of plasmid pSC101.
AB  - The Rep protein, a replication initiator of plasmid pSC101, also functions as an
      autorepressor for its own structure gene, rep, through binding to the operator
      which consists of imperfectly dyad-symmetric (pseudo-symmetric) sequences, IR-1
      and IR-2. In order to define the DNA binding motif of Rep, we have analyzed its
      binding affinity for each half repeat of the IR sequences and found that the
      right half of IR-2 was the preferred sequence for Rep, although its affinity was
      much lower than those of the IR sequences. Next, dimeric sequences of each half
      repeat with different configurations, head to head (the same configuration as
      natural IRs), head to tail, and tail to tail, were constructed and their
      affinities for Rep were examined. Almost all of sequences with the head-to-head
      configuration had binding affinity for Rep but these, including even the
      symmetric sequence of the right half of IR-2, exhibited lower Rep-binding
      abilities than natural IR sequences. We presume a pseudo-symmetric sequence,
      5'GGNNTAGNNATTNNNATNN(N)CTAGNCC3', to be the Rep-binding motif from a sequence
      comparison. Some single-base substitution experiments confirmed the motif and
      suggested that each subunit of the Rep dimer recognizes each half repeat of IR
      asymmetrically.

PMID- 8276767
TI  - Interaction of subtilisin BPN' and recombinant Streptomyces subtilisin inhibitors
      with substituted P1 site residues.
AB  - Kinetic analysis was performed on the interaction between subtilisin BPN' and
      recombinant species of a proteinaceous proteinase inhibitor, Streptomyces
      subtilisin inhibitor (SSI), of which the P1 site amino acid residue, Met73, was
      replaced by site-directed mutagenesis. The inhibitor constant, Ki, was determined
      from the residual enzyme activity by using a peptide substrate. The rate constant
      of binding, kon, and the rate constant of dissociation, koff, were determined
      from a progress curve of the substrate hydrolysis in the presence of the
      inhibitor by using newly derived equations. A recombinant SSI in which Met73 was
      replaced by Ile showed an affinity (1/Ki) toward subtilisin BPN' of only about 7%
      of that of the wild-type SSI, and the kinetic analysis revealed that the increase
      of koff was responsible for this difference. The affinity of other SSI mutants in
      which Met73 was replaced by Glu or Asp decreased significantly as pH became
      increasingly alkaline. The decrease in the affinity of these recombinants was due
      to the decrease of kon rather than the increase of koff. Stopped-flow studies
      revealed that the binding reaction was reconcilable with a two-step mechanism,
      and the kinetic parameters for each step were obtained for the binding of the
      enzyme and recombinant SSIs.

PMID- 8276768
TI  - Chemical structures of two subunits, A-subunit and B-subunit, of galactose
      specific isolectins from Erythrina variegata seeds.
AB  - We previously isolated galactose-specific isolectins, EVLI, EVLII, and EVLIII,
      from the Erythrina variegata seeds [J. Chromatogr. 597, 207-211 (1992)]. The
      amino acid sequences of the two subunits, A- and B-subunits, of which the
      isolectins are composed, were determined. A comparison of the amino acid
      sequences of tryptic peptides from the two subunits revealed seven amino acid
      substitutions. Among them, Asn46, to which the oligosaccharide chain is linked in
      the A-subunit, is replaced by Asp46 in the B-subunit, causing the B-subunit to
      lack one glycosylation site. The N-linked oligosaccharides of these subunits were
      also analyzed. The N-linked oligosaccharides were first liberated by
      hydrazinolysis. After N-acetylation, the reducing ends of the oligosaccharides
      were coupled with 2-aminopyridine, and then the pyridylamino (PA-) derivatives
      were purified by gel filtration and HPLC on an ODS-silica column. One major sugar
      chain, accounting for more than 98% of the total, was purified from both species.
      The structure of this major sugar chain was established to be Man alpha 6(Man
      alpha 3)(Xyl beta 2)Man beta 4GlcNAc beta 4(Fuc alpha 3)GlcNAc. This finding that
      there is no structural difference of the sugar chains linked to the two subunits
      of E. variegata lectins, together with the results of amino acid sequence
      comparisons, indicates that the difference in molecular mass of these two
      subunits results almost wholly from the difference in the number of
      oligosaccharides linked to them.

PMID- 8276769
TI  - Expression of the mC26 gene encoding GlyCAM-1 in the lactating mouse mammary
      gland.
AB  - We previously reported the partial sequence of a cloned genomic DNA, mC26, which
      codes for a protein highly expressed in the lactating mouse mammary gland [mC26:
      Satow et al. (1986) J. Biochem. 99, 1639-1643; partial sequence: Kawamura et al.
      (1987) J. Biochem. 101, 103-110]. In this study, we sequenced the EcoRI-HindIII
      fragment (5,394 bp) of this gene and found that this gene contains a sequence
      completely (100%) homologous to the cDNA sequence currently reported to code for
      GlyCAM-1, a putative ligand for L-selectin. We show by means of an RNA protection
      assay that the mRNA of this gene is expressed in the mammary glands of lactating
      mice as well as in the lymph nodes. Semi-quantitative analysis of expression of
      the mC26 gene in the mammary glands revealed that the amount of mRNA was not
      detectable in the early stage of pregnancy, increased in the late stage, and
      remained quite abundant during lactation. The potential role of this gene highly
      expressed in the mammary gland in a stage-specific and tissue-specific manner is
      discussed.

PMID- 8276770
TI  - Interaction of Streptomyces subtilisin inhibitor (SSI) with Streptomyces griseus
      metallo-endopeptidase II (SGMP II).
AB  - We have unexpectedly found that Streptomyces subtilisin inhibitor (SSI) and some
      other similar serine protease inhibitors produced by Streptomycetes strongly
      inhibit Streptomyces griseus metallo-endopeptidase II (SGMP II) [Kajiwara, K. et
      al. (1991) J. Biochem. 110, 350-354]. In order to elucidate the mode of their
      unusual interaction with SGMP II in more detail, we prepared twelve kinds of SSI
      analogues, in which one or two amino acid residues in the peptide segment from
      Thr64 to Val74 of wild-type SSI had been replaced or deleted by site-directed
      mutagenesis, and determined the dissociation constants of their complexes with
      SGMP II. Six analogues among them showed dissociation constants one order of
      magnitude lower than that of the wild type. Three had higher values. The results
      suggest that at least some residues in this segment are interacting with SGMP II
      in the complex. We also prepared an SSI mutant in which the disulfide bridge
      between Cys71 and Cys101 had been eliminated by replacing the two Cys residues
      with Ser residues. This mutated SSI inhibited SGMP II as strongly as the wild
      type SSI did. While peptide bonds in the wild-type molecule did not suffer from
      the hydrolytic action of SGMP II except those at the amino-terminal fragile
      portion, the Pro72-Met73 bond of the mutant was specifically cleaved by the
      enzyme. This peptide bond, therefore, seems to play the role of the reactive site
      in the interaction of SSI with SGMP II.

PMID- 8276771
TI  - Hemolytic properties under hydrostatic pressure of neuraminidase- or protease
      treated human erythrocytes.
AB  - We investigated the hemolytic properties under high pressure (200 MPa) of human
      erythrocytes in which sialic acids and glycopeptides had been removed from
      membrane surface by using neuraminidase and proteolytic enzymes such as trypsin
      and chymotrypsin, respectively. The degree of hemolysis increased in proportion
      to the amounts of sialic acids or glycopeptides released from intact
      erythrocytes. Studies of the time course of hemolysis showed that upon enzymatic
      digestion erythrocyte membranes became more fragile against high pressure. Such
      fragility decreased in the presence of chlorpromazine and trifluoperazine but was
      unaffected by chlorpromazine methiodide or indomethacin. Furthermore, the effect
      of cross-linking of membrane proteins by diamide on the fragility was examined.
      The degree of hemolysis at 200 MPa increased upon removal of sialic acids from
      red cells in which spectrin is mainly cross-linked, but did not upon enzymatic
      digestion of red cells in which glycophorins, in addition to cross-linking of
      themselves, are included in the large-molecular-weight aggregates formed by cross
      linking of the membrane skeleton with transmembrane proteins. In the latter case,
      however, upon reduction of the cross-linking by dithiothreitol the effect of
      enzymatic digestion appeared again. On the other hand, such an enzymatic
      digestion effect on osmotic hemolysis was not observed either in intact
      erythrocytes or in diamide-treated red cells. These results suggest that the
      interaction of the cytoplasmic domains of glycophorins with cytoskeletal proteins
      may be weakened by enzymatic digestion of the exofacial domains of glycophorins.

PMID- 8276772
TI  - Increased expression of cofilin in dystrophic chicken and mouse skeletal muscles.
AB  - A monoclonal antibody (McAb) specific for actin depolymerizing factor (ADF) was
      prepared. With this and previously prepared anti-cofilin McAb (MAB-22) and other
      antibodies, the expression of cofilin and ADF in the muscles of dystrophic (NH
      413) chicken and dystrophic (C57BL/6J dy/dy) mice was compared with that in
      normal control animals by immunoblotting and immunocytochemical methods. Since
      cofilin expression is down-regulated during normal postnatal development of
      skeletal muscles [Abe et al. (1989) J. Biochem. 106, 696-702], cofilin was
      detected in the breast (pectoralis) muscle of normal adult chicken and the leg
      (femoris and tibialis anterior) muscles of normal mice only at a low level. ADF
      was not detectable in adult skeletal muscles. However, a significant increase of
      cofilin amount, but not of ADF amount, was observed in these muscles of the
      dystrophic animals, when the symptom of muscular dystrophy became evident. In
      order to localize cofilin in individual muscle fibers, serial cryosections of the
      dystrophic chicken muscle were examined with anti-cofilin antibody (MAB-22). The
      antibody stained cells of different size in the dystrophic muscle, indicating
      that cofilin expression was induced in the regenerating muscle cells as well as
      in the pre-existing myofibers. We suggest that cofilin is involved in disassembly
      or reorganization of actin in the dystrophic muscle.

PMID- 8276773
TI  - Elimination of plasma phosphatidylcholine hydroperoxide by a seleno-organic
      compound, Ebselen.
AB  - The effects of a seleno-organic compound, Ebselen [2-phenyl-1,2-benzoisoselenazol
      3(2H)-one], on phospholipid hydroperoxide levels in in vitro and in vivo systems
      were examined by using high-performance liquid chromatography with
      chemiluminescence detection (CL-HPLC) as a tool for measuring the hydroperoxide.
      In in vitro systems, the phosphatidylcholine hydroperoxide (PCOOH) content in
      phosphatidylcholine (PC) liposomes was significantly reduced by co-incubation
      with exogenously added Ebselen; 85, 97, and 99.6% of PCOOH was eliminated with 1,
      10, and 100 microM Ebselen, respectively. In human plasma, 79, 87, and 86% of
      PCOOH was eliminated after the incubation with 1, 10, and 100 microM Ebselen,
      respectively. In an in vivo study involving single oral administration of Ebselen
      (10, 30, and 100 mg/kg rat) to rats, plasma PCOOH (48.8 nM for Ebselen-untreated
      rat) was significantly decreased to 26.3, 5.6, and 3.3 nM at 2 h after the
      administration and 6.7, 7.4, and 4.8 nM at 4 h after the administration,
      respectively. These in vivo effects on plasma PCOOH elimination depended on both
      the dose and the time after the administration. Maximum decrease of plasma PCOOH
      appeared around 2-4 h after oral administration. The liver and red blood cell
      PCOOH levels were not affected by oral Ebselen under the present conditions.
      These findings indicate that the Ebselen may be a potent agent for lowering
      plasma PCOOH levels in vivo.

PMID- 8276774
TI  - Regulation of hsp70 synthesis induced by cupric sulfate and zinc sulfate in
      thermotolerant HeLa cells.
AB  - Upon exposure to the heavy metals copper and zinc, a large amount of 70,000-Da
      heat shock protein (hsp70) was synthesized in normal, non-thermotolerant (NT)
      HeLa cells, whereas only a little increase of hsp70 synthesis was observed in
      thermotolerant (TT) cells. To determine the inhibition mechanism of hsp70
      induction in the TT cells, we first analyzed the hsp70 mRNA of these cells. Hsp70
      mRNA in the NT cells increased immediately after exposure to these metals. In TT
      cells, however, the increase of hsp70 mRNA was delayed, even though it eventually
      increased to a similar or slightly lower level compared with NT cells. Further
      analysis of the activation of heat shock transcription factor (HSF) showed that a
      significant activation of HSF was observed immediately after exposure to these
      metals in the NT cells, whereas the activation of HSF was initially repressed in
      the TT cells. Thus, the decreased induction of hsp70 synthesis observed in the TT
      cells seemed to be due to the reduced translation of hsp70 mRNA and also in part
      to the reduced activation of HSF. Furthermore, by the gel mobility shift assay
      using anti-hsp70 antibody, the association of copper- and zinc-activated HSF with
      hsp70 was observed in both NT and TT cells. The amount of HSF-hsp70 complex was
      prominent in TT cells, in which the hsp70 content was 5 to 10 times higher than
      that in the NT cells. These findings strongly suggest that the activity of HSF is
      negatively regulated by hsp70 in the TT cells.

PMID- 8276775
TI  - Cycling of two endogenous lysosomal membrane proteins, lamp-2 and acid
      phosphatase, between the cell surface and lysosomes in cultured rat hepatocytes.
AB  - Our previous studies provided evidence that a 107-kDa major lysosomal membrane
      glycoprotein termed lamp-1 shuttles between lysosomes and the plasma membrane
      along the endocytic pathway in rat hepatic cells [Furuno et al. (1989) J.
      Biochem. 106, 708-716; Furuno et al. (1989) J. Biochem. 106, 717-722]. In the
      present study, we investigated the movement of a 96-kDa major lysosomal membrane
      glycoprotein, referred to as lamp-2, and lysosomal acid phosphatase (LAP) in the
      endocytic membrane transport system of cultured rat hepatocytes. Fab' fragments
      of anti-lamp-2 and anti-LAP antibodies conjugated with horseradish peroxidase
      (HRP) were used as probes to analyze quantitatively the transport of these two
      membrane proteins from the cell surface to lysosomes. After the addition of HRP
      anti-lamp-2 and anti-LAP Fab' fragments to the culture medium, the delivery of
      the antibody conjugates to lysosomes was examined by cell fractionation on a
      Percoll density gradient. The amount of these HRP tracers in the lysosomal
      fraction became larger as the period of cell incubation was increased. Km values
      for uptake of HRP-anti-lamp-2, and LAP Fab' fragments were 0.74 and 0.62 microM,
      respectively, which were comparable to that of HRP-anti-lamp-1 Fab' (0.57
      microM). The endocytic process of the two HRP-antibodies continued for an
      extended period in the cells exposed to the protein synthesis inhibitor,
      cycloheximide. Furthermore, we measured the transit times of HRP-anti-lamp-1,
      anti-lamp-2, and anti-LAP Fab' fragments from the cell surface to
      lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276776
TI  - Comparison of DNA-binding properties between BTEB and Sp1.
AB  - We have expressed truncated forms of BTEB and Sp1 in Escherichia coli and
      investigated the DNA-binding properties of the two proteins. The two proteins as
      well as their chimeric proteins protected the same DNA region in the BTE sequence
      (a GC box in the P-4501A1 gene) as examined by ortho-phenanthroline-Cu
      footprinting. The region overlapped nearly perfectly with the GC box consensus
      sequence. Methylation interference footprinting revealed that all the guanines
      within the region and two other guanines in the close vicinity interacted with
      the proteins. Competitive gel mobility shift assay using various synthetic
      oligonucleotides of the GC box sequences as the competitors demonstrated that
      BTEB and Sp1 have similar sequence specificities for DNA binding. We have
      purified the bacterially expressed BTEB and measured the dissociation constant of
      the BTEB-BTE complex using gel mobility shift assay. The dissociation constant
      was (3.0 +/- 1.0) x 10(-10) M and was comparable to that of Sp1 binding to a GC
      box. Taken together, these findings indicate that the binding modes of BTEB and
      Sp1 to the GC box are similar to each other.

PMID- 8276777
TI  - Inhibition of neurite outgrowth in neuroblastoma cells by sphingosine.
AB  - Mouse neuroblastoma NS-20Y cells were induced to grow neurites by removal of
      serum from the medium. The percentage of cells with neurites reached about 50-60%
      after 24 h, whereas in medium containing 10% serum only a few cells (1-3%) were
      bearing neurites. Sphingosine inhibited the neuritogenesis in serum-free medium
      in a dose-dependent manner; a maximal effect was observed at 1-2 microM.
      Sphingosine also caused retraction of neurites which had been induced to extend
      in serum-free medium. N,N-Dimethylsphingosine was 10 times more potent in
      preventing neurite outgrowth, and N-acetylsphingosine was 10 times less effective
      compared to sphingosine. However, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine
      (H-7) did not inhibit the extension of neurites. Neurite outgrowth in serum-free
      medium and its inhibition by sphingosine were still observed in the cells made
      protein kinase C-deficient by prolonged treatment with phorbol ester. These
      results suggest that the effect of sphingosine is not mediated by inhibition of
      protein kinase C.

PMID- 8276778
TI  - Functional reconstitution of the putative Escherichia coli osmosensor, KdpD, into
      liposomes.
AB  - Expression of the Escherichia coli kdpABC operon, which is responsible for a high
      affinity potassium-uptake system, is regulated in response to a change in the
      medium osmolarity. We present the first in vivo evidence that the putative
      osmosensor (kinase), KdpD, plays a crucial role in the osmotic regulation of
      kdpABC expression. We then isolated the intact form of KdpD from the cytoplasmic
      membrane with a mild non-ionic detergent, dodecyl maloside, as a soluble form.
      The solubilized KdpD itself did not exhibit the ability to phosphorylate the
      cognate response-regulator, KdpE. Upon reconstitution into liposomes, however,
      KdpD exhibited its kinase activity. Thus, using this partially purified form of
      KdpD, we succeeded in reconstituting KdpD-bearing liposomes that are fully
      functional in terms of their ability to phosphorylate the cognate positive
      regulator, KdpE. By adopting this in vitro method, some in vivo conditions were
      mimicked in order to address the molecular mechanism underlying signal
      transduction mediated by KdpD. Some catalytic properties of KdpD in liposomes are
      also presented.

PMID- 8276779
TI  - The insulin signaling system.

PMID- 8276780
TI  - Functional domains of the insulin receptor responsible for chemotactic signaling.
AB  - The insulin receptor mediates a variety of cellular responses to insulin,
      including glucose transport, endocytosis, and cell proliferation. The role of the
      insulin receptor in mediating cellular motility has not, however, been
      extensively investigated. In this report, we demonstrate that chinese hamster
      ovary (CHO) cells that normally have low concentrations of insulin receptor
      display chemotaxis toward insulin after overexpression of the wild type human
      insulin receptor. Chemotaxis toward insulin proceeded through a pertussis toxin
      sensitive pathway and required both tyrosine kinase activity and tyrosine
      autophosphorylation of the regulatory region of the beta-subunit. In contrast,
      the autophosphorylation sites in the carboxyl terminus of the receptor were not
      required for chemotactic activity. A mutation in the juxtamembrane region, which
      disabled tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1),
      also prevented the chemotactic response, suggesting a possible role for IRS-1 in
      chemotactic signaling. In the absence of insulin receptor, however, the presence
      of excess transfected IRS-1 was not sufficient to mediate chemotaxis toward
      insulin. These results demonstrate that the intact insulin receptor can stimulate
      a chemotactic signaling pathway and that this initial pathway more closely
      correlates with that for insulin-stimulated cell proliferation than for insulin
      stimulated receptor endocytosis.

PMID- 8276781
TI  - Differential regulation of respiratory chain subunits by a CREB-dependent signal
      transduction pathway. Role of cyclic AMP in cytochrome c and COXIV gene
      expression.
AB  - In vertebrate organisms, the molecular mechanisms by which extracellular signals
      regulate mitochondrial function and biogenesis are largely unknown. We have
      previously identified multiple cis-acting elements in both cytochrome c and
      cytochrome oxidase subunit IV (COXIV) genes that are likely targets for the
      regulated expression of respiratory chain components. We now demonstrate that
      cytochrome c but not COXIV mRNA is induced by cAMP through a mechanism involving
      transcriptional activation. Maximal induction occurs within 3 h and does not
      require de novo protein synthesis. The differential response of these genes is
      mediated by two distinct cAMP response elements (CREs) in the cytochrome c
      promoter region. Both elements function independently to drive cAMP-dependent
      expression from a heterologous promoter and within the proper cytochrome c
      promoter context. In addition, the binding properties of both elements to nuclear
      factors were characterized by competition DNase I footprinting, methylation
      interference footprinting, site-directed mutagenesis, and UV-induced DNA-protein
      cross-linking. The results are all consistent with the specific recognition of
      both CREs by CRE binding protein (CREB). A highly purified preparation of
      recombinant CREB formed a specific complex with each of the cytochrome c CREs
      identical to that formed with a crude nuclear fraction. In addition, the trans
      activation of cytochrome c gene expression by recombinant CREB and protein kinase
      A in transfected cells was completely dependent on functional CREs within the
      promoter. These results establish that respiratory chain gene expression can be
      regulated directly by cAMP through a CREB-dependent signal transduction pathway.

PMID- 8276782
TI  - Differential structural requirements of heparin and heparan sulfate proteoglycans
      that promote binding of basic fibroblast growth factor to its receptor.
AB  - Heparan sulfate proteoglycans (HSPG) are obligatory for receptor binding and
      mitogenic activity of basic fibroblast growth factor (bFGF). The capacity of
      various species of heparin and heparan sulfate (HS) to promote bFGF receptor
      binding was investigated using both Chinese hamster ovary mutant cells deficient
      in cell surface HSPG and a soluble bFGF receptor-alkaline phosphatase fusion
      protein. Highly sulfated oligosaccharides were more effective than medium and low
      sulfate fractions of the same size oligosaccharide. O-Sulfation in heparin was
      found to be critical for its capacity to promote binding of bFGF to its
      receptors. The highest level of bFGF-receptor binding was achieved in the
      presence of over-sulfated heparin fragments (% sulfur > 14) regardless of whether
      the N-position was sulfated or acetylated. Unlike receptor binding of bFGF which
      requires oligosaccharides containing at least 8-10 sugar units, displacement of
      heparin- or HS-bound bFGF was obtained by oligosaccharides containing as little
      as four sugar units and by an N-sulfated, O-desulfated heparin fragment (% sulfur
      = 5.3). A preparation of total cell surface-derived HS induced bFGF receptor
      binding. A preliminary survey of several defined and affinity purified species of
      cell surface HSPG, including syndecan, fibroglycan, and glypican failed to
      identify natural HSPG that promote high affinity receptor binding of bFGF. A
      similar lack of activity was observed with species of HS isolated from bovine
      arterial tissue and characterized for their effect on vascular smooth muscle cell
      proliferation. Moreover, most of these species of HS inhibited in a dose
      dependent manner the restoration of bFGF-receptor binding induced by heparin or
      by total HSPG. These results suggest the involvement of defined heparin-like
      oligosaccharide sequences and unique species of cell surface and extracellular
      matrix HS in the regulation of bFGF receptor binding and biological activity.

PMID- 8276783
TI  - Purification, characterization, and high performance liquid chromatography assay
      of Salmonella glucose-1-phosphate cytidylyltransferase from the cloned rfbF gene.
AB  - We report the purification and characterization of glucose-1-phosphate
      cytidylyltransferase, the first of five enzymes committed to biosynthesis of CDP
      D-abequose from Salmonella enterica strain LT2. The purification was greatly
      facilitated by using a cloned rfbF gene encoding this enzyme. Pure enzyme was
      obtained by 64-fold enrichment in three chromatography steps. The NH2-terminal
      sequence of the purified enzyme was in agreement with the sequence predicted from
      the nucleotide sequence of the rfbF gene. The SDS-polyacrylamide gel
      electrophoresis estimated subunit M(r) of 31,000 agrees well with the M(r) of
      29,035 calculated from the amino acid composition deduced from the nucleotide
      sequence of the rfbF gene. The glucose-1-phosphate cytidylyltransferase catalyzes
      a reversible bimolecular group transfer reaction and steady-state kinetic
      measurements, including product inhibition patterns, indicate that this reaction
      proceeds by a "ping-pong" type of mechanism. The Km values for CTP, alpha-D
      glucose 1-phosphate, CDP-D-glucose, and pyrophosphate are 0.28, 0.64, 0.11, and
      1.89 mM, respectively.

PMID- 8276784
TI  - Crystal structure of RNase T1 with 3'-guanylic acid and guanosine.
AB  - A modified method for the synthesis and separation of endo and exo guanosine
      2',3'-cyclophosphorothioate (cGPS) has been developed. The exo diastereoisomer
      has been co-crystallized with RNase T1. cGPS is known to be a RNase T1 inhibitor
      but is also a very slow substrate. It was hydrolyzed during the crystallization,
      leaving 3'-guanylic acid (3'-GMP) in the active site. As a guanosine was also
      found to be bound in a subsite, the enzyme contains the products of the reaction
      of guanylyl-3',5'-guanosine. The structure was refined to a resolution of 1.7 A
      and yielded a final R value of 14.5%. In contrast to previous 3'-GMP complexes of
      RNase T1, the ribose phosphate moiety of the inhibitor is in contact with all the
      active site residues. The phosphate forms hydrogen bonds with Asn36, Tyr38,
      Arg77, His92, and with Asn49 from a symmetry-related molecule. The ribose 2'-OH
      is hydrogen-bonded to both Glu58 and His40. The interactions in the active site
      of the present structure are compared to those found in the 2'-GMP complex of
      RNase T1.

PMID- 8276785
TI  - Interleukin 1 alpha stimulates nuclear phospholipase C in human osteosarcoma SaOS
      2 cells.
AB  - Interleukin 1 (IL-1) is one of the most potent stimulators of bone resorption.
      However, the early biochemical events elicited by IL-1 receptor binding are not
      fully understood. Here we show that in human osteosarcoma SaOS-2 cells the
      treatment with IL-1 alpha is able to evoke a rapid and transient increase of
      nuclear phospholipase C (PLC) activity. A parallel decrease of nuclear
      phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate is
      observed. All these events are strictly confined to the nuclear compartment
      without affecting the cytoplasmatic inositol lipid pool. In addition we show that
      by Western blot analysis with specific monoclonal antibodies the PLC gamma is
      located both in the cytoplasm and in the nucleus, while PLC beta appears
      exclusively localized in the nucleus. Moreover, the increase of PLC activity in
      response to IL-1 alpha is completely neutralized by monoclonal antibody against
      the beta-form. While confirming the existence of an autonomous nuclear
      phosphoinositide signaling system, our data clearly indicate that in SaOS-2 cells
      one of the earliest events following IL-1 alpha treatment is the breakdown of
      nuclear phosphatidylinositol monophosphate and phosphatidylinositol bisphosphate
      because of the activation of a specific nuclear PLC isoform.

PMID- 8276786
TI  - EPR evidence that the M+ radical, which is observed in three site-directed
      mutants of photosystem II, is a tyrosine radical.
AB  - Isotopic labeling of Synechocystis sp. PCC 6803 and EPR spectroscopy have been
      used to demonstrate that photosystem II contains two redox active tyrosines, D
      and Z (Barry, B. A. and Babcock, G. T. (1987) Proc. Natl. Acad. Sci. U.S.A. 84,
      7099-7103; Boerner, R. J. and Barry, B. A. (1993) J. Biol. Chem. 268, 17151
      17154). Another organic radical, M+, has recently been observed in site-directed
      mutants in which a non-redox active amino acid is substituted at either the
      putative D or putative Z sites (Boerner, R. J., Bixby, K. A., Nguyen, A. P.,
      Noren, G. H., Debus, R. J., and Barry, B. A. (1993) J. Biol. Chem. 268, 1817
      1823; Noren, G. H., and Barry, B. A. (1992) Biochemistry 31, 3335-3342). Here, we
      use isotopic labeling to determine the chemical identity of M+. Upon
      incorporation of perdeuterated tyrosine into photosystem II, the M+ EPR signal
      narrows to approximately 12-13 G. Labeling with 3,5-deuterated tyrosine results
      in an isotropic doublet with splittings of 11 G. Our results show that M+ is a
      tyrosine radical with unique spectroscopic properties.

PMID- 8276787
TI  - Identification and isolation of glycoproteins that translocate to the cell
      surface from GLUT4-enriched vesicles in an insulin-dependent fashion.
AB  - It has previously been shown that in fat cells, the intracellular reservoir of
      the glucose transporter isoform GLUT4 consists of a membrane vesicle population
      highly enriched in this transporter (approximately 15% of the protein content)
      that has a relatively simple protein pattern as revealed by SDS-polyacrylamide
      gel electrophoresis and silver staining (Zorzano, A., Wilkinson, W., Kotliar, N.,
      Thoidis, G., Wadzinski, B. E., Ruoho, A. E., and Pilch, P. F. (1989) J. Biol.
      Chem. 264, 12358-12363). Upon exposure of adipocytes to insulin, the cell-surface
      (plasma membrane) content of GLUT4 is dramatically enhanced, and this transporter
      appears to continually cycle from intracellular vesicles to the plasma membrane.
      To identify other proteins that may recycle in a similar fashion to GLUT4 and
      that may participate in the insulin-dependent alteration in the cellular location
      of GLUT4 and other membrane proteins, we performed immunoadsorption of GLUT4
      enriched vesicles together with biotinylation of membranes using a cell
      impermeant analog of biotin. We find that immunoadsorbed GLUT4-containing
      vesicles can be fractionated into Triton X-100-soluble and -insoluble fractions.
      The first includes three major glycoprotein components with molecular masses of
      110, 160, and 230 kDa and a few minor polypeptides with lower molecular masses. A
      Triton X-100-resistant fraction consists of GLUT4 and an approximately 25-kDa
      protein. All three major Triton-soluble proteins (110, 160, and 230 kDa) isolated
      from the immunoimmobilized vesicles on wheat germ agglutinin-agarose are strongly
      biotinylated in an insulin-dependent fashion, i.e. they cycle to and from the
      cell surface in an apparently identical manner to GLUT4. Sequence analysis of two
      tryptic fragments from p160 reveals that it is a novel protein containing
      sequence with no homology to known proteins.

PMID- 8276788
TI  - The biochemical basis for the apparent defect of soluble mutant tissue factor in
      enhancing the proteolytic activities of factor VIIa.
AB  - Tissue factor (TF), an integral membrane protein, is the cofactor for the serine
      protease, coagulation factor VIIa (FVIIa). Previous studies of the isolated
      extracellular domain of TF (sTF) reported a kcat for factor X (FX) activation by
      the sTF.VIIa complex only 4% that of wild-type TF.VIIa and furthermore, a
      complete inability of sTF to support FVII autoactivation. We now report that in
      the presence of poly(L-lysine), sTF promoted both FX activation and FVII
      autoactivation, the latter with an apparent second-order rate constant higher
      than reported previously for wild-type TF in phospholipid vesicles. This led us
      to reexamine the cofactor ability of sTF, using high concentrations of
      phospholipid to promote nearly quantitative binding of sTF.VII(a) complexes to
      the phospholipid surface. Rate constants for the activation of FX or FVII by
      sTF.VIIa were similar to those of wild-type TF.VIIa, indicating that the apparent
      deficiency of sTF is largely attributable to kinetic consequences of relatively
      weak affinity of FVIIa (and sTF.VIIa) for phospholipid surfaces in these surface
      dependent reactions, compared with TF being embedded in the membrane. This
      supports the notion that sTF recapitulates the protein-protein interactions of
      wild-type TF with high, and possibly full, catalytic activity. It also provides a
      biochemical explanation for the specificity of our recently described, sTF-based
      clotting assay for plasma FVIIa.

PMID- 8276789
TI  - Mechanism of p-hydroxyphenylacetate-3-hydroxylase. A two-protein enzyme.
AB  - p-Hydroxyphenylacetate-3-hydroxylase purified from Pseudomonas putida is a two
      protein enzyme requiring a flavoprotein and a coupling protein for productive
      hydroxylation (Arunachalam, U., Massey, V., and Vaidyanathan, C. S. (1992) J.
      Biol. Chem. 267, 25848-25855). This paper presents information on the mechanism
      of the enzyme from absorbance and fluorescence stopped-flow studies. The
      reduction of the substrate-free flavoprotein by NADH was slow and was not altered
      by the presence of the coupling protein. In contrast, the coupling protein has a
      dramatic effect in the oxidative half-reaction. The flavoprotein when present
      alone, both in the absence and presence of the aromatic substrate, reacts in a
      second-order fashion with oxygen to form oxidized flavoprotein, with no
      indication of flavin-oxygen intermediates. However, an intermediate identified as
      the C4a-flavin hydroperoxide is stabilized when the flavoprotein-coupling protein
      complex reacts with oxygen in the absence of the aromatic substrate, p
      hydroxyphenylacetate, and at least three flavin-oxygen intermediates, attributed
      to the anionic (I) and protonated (I*) forms of the flavin hydroperoxide and the
      hydroxyflavin (III), are formed in the oxidative half-reaction in the presence of
      the aromatic substrate. A reaction mechanism for the two-protein complex is
      proposed in which the aromatic substrate has little effect on the rate of
      reduction of the enzyme flavin but has strict control in the oxidative half
      reaction. In this phase the flavin hydroperoxide is remarkably stable in the
      absence of the substrate but disappears rapidly upon encountering the aromatic
      substrate.

PMID- 8276790
TI  - Differential modulation of Na-HCO3 cotransport and Na-H exchange by pH in
      basolateral membrane vesicles of rat distal colon.
AB  - This study was designed to investigate the function of intravesicular proton on
      two pH gradient-dependent transport processes, a novel Na-HCO3 cotransport and a
      Na-H exchange, that are present in basolateral membrane vesicles of rat distal
      colon. Increasing intravesicular proton concentration saturated 22Na uptake via
      both Na-H exchange and Na-HCO3 cotransport; reduced the apparent Km for sodium
      for Na-H exchange from 94.9 to 35.6 mM, without alteration in the Vmax; but
      enhanced the Vmax for Na-HCO3 cotransport from 4.3 to 11.7 nmol/mg protein.6 s,
      while not changing the Km for sodium. The effect of a 10-fold proton
      concentration gradient at two different absolute proton concentrations on both
      systems was also determined. 22Na uptake via Na-HCO3 cotransport, but not via Na
      H exchange, was enhanced at the higher proton concentration, indicating that the
      magnitude of the proton concentration gradient is primarily responsible for
      proton stimulation of Na-H exchange, whereas the absolute proton concentration is
      critical for proton enhancement of Na-HCO3 cotransport. These studies also
      demonstrate saturation of both transport systems as a function of intravesicular
      proton concentration without an exponential component. These results indicate
      that proton stimulated Na-H exchange and Na-HCO3 cotransport are regulated by
      distinct and separate mechanisms that may reflect their different cellular
      functions.

PMID- 8276791
TI  - Molecular characterization of hasA from an operon required for hyaluronic acid
      synthesis in group A streptococci.
AB  - The mechanism by which group A streptococci produce the antiphagocytic
      hyaluronate (hyaluronic acid) capsule is incompletely understood. Enzymes known
      to be essential for synthesis of this polysaccharide include the membrane
      associated hyaluronate synthase as well as those required for production of the
      substrate sugars UDP-N-acetylglucosamine and UDP-glucuronic acid. In this study,
      a Tn916 insertion that inactivates hyaluronate synthetic activity was localized
      to a gene designated hasA in the hyaluronic acid synthesis operon. This gene has
      recently been preliminarily identified as the group A streptococcal hyaluronate
      synthase. The DNA sequence and transcription start site of hasA were determined,
      and the predicted HasA protein was shown to have characteristics of a membrane
      protein. Amino acid sequence homology suggests that HasA is related to a family
      of proteins involved in polysaccharide production and cell differentiation.
      Finally, in addition to the loss of hyaluronate synthase activity, the
      hasA::Tn916 insertion was demonstrated to correlate with a loss of UDP-glucuronic
      acid dehydrogenase activity. These results suggest that the genes required for
      hyaluronate synthase activity and production of the UDP-glucuronic acid substrate
      are transcribed as a unit in group A streptococci.

PMID- 8276792
TI  - A novel cDNA restores reduced folate carrier activity and methotrexate
      sensitivity to transport deficient cells.
AB  - Mammalian cells accumulate reduced folates and methotrexate, a folate antagonist,
      through the reduced-folate carrier (RFC) (Goldman, I.D., Lichtenstein, N.S., and
      Oliverio, V.T. (1968) J. Biol. Chem. 243, 5007-5017). This study describes the
      isolation and expression of a cDNA clone that restores RFC activity to human
      breast cancer cells defective in this transporter. The cDNA cancer cells
      defective in this transporter. The cDNA codes for a peptide (mRFC1) of 58 kDa,
      whose hydropathy plot, resembling those of mammalian sugar transporters, predicts
      that it may be a member of a superfamily of transporter genes. Transfection of
      methotrexate-resistant (MTXR) ZR-75-1 cells with an expression vector, pRFC1,
      that codes for this peptide restores their ability to accumulate methotrexate.
      Furthermore, transport of methotrexate into pRFC1-transfected cells is blocked by
      a 10-fold molar excess of the reduced folate, 5-formyltetrahydrofolic acid, but
      is unaffected by folic acid. The increase in methotrexate uptake that is observed
      in pRFC1-transfected MTXR ZR-75-1 cells reverses their resistance to this
      antitumor agent.

PMID- 8276793
TI  - cDNA cloning and characterization of a vitamin D3 hydroxylase-associated protein.
AB  - We previously reported the generation of monoclonal antibodies which
      immunoprecipitate a fraction of the total chick kidney 1,25-dihydroxyvitamin D3
      24R-hydroxylase activity. These antibodies were used to screen a chick kidney
      lambda gt11 cDNA library resulting in the isolation of a full-length cDNA
      encoding a protein that is not the 1,25-dihydroxyvitamin D3-24R-hydroxylase but
      another protein we term the vitamin D3 hydroxylase-associated protein (VDHAP).
      The deduced amino acid sequence agreed with an NH2-terminal amino acid sequence
      from the isolated VDHAP. Gene and protein bank search did not identify homology
      to known sequences or functional domains in the VDHAP cDNA. VDHAP mRNA levels are
      not altered by conditions which either induce 1,25-dihydroxyvitamin D3-24R
      hydroxylase activity (78-fold) or 25-hydroxyvitamin D3-1 alpha-hydroxylase
      activity (30-fold). Northern analysis of poly(A)+ RNA from chick tissues revealed
      VDHAP only in kidney. Cellular fractionation experiments demonstrated that VDHAP
      and the 25-hydroxyvitamin D3-1 alpha-hydroxylase are colocalized in the inner
      membrane of mitochondria. The VDHAP antibody immunoprecipitates 14% of the total
      1,25-dihydroxyvitamin D3-24R-hydroxylase activity (7-fold over background) and
      immunoprecipitates 21% of the total 25-hydroxyvitamin D3-1 alpha-hydroxylase
      activity (2-fold over background). VDHAP is a novel chick kidney-specific inner
      membrane protein of mitochondria, which associates with a fraction of the 1,25
      dihydroxyvitamin D3-24R-hydroxylase and 25-hydroxyvitamin D3-1 alpha-hydroxylase.

PMID- 8276794
TI  - Regulation of the sarcoplasmic reticulum ryanodine receptor by inorganic
      phosphate.
AB  - To better understand the mechanisms regulating myoplasmic Ca2+ during muscle
      activity, we have examined the effect of inorganic phosphate (P(i)) on the
      ryanodine receptor (RyR) Ca2+ release channel of the sarcoplasmic reticulum (SR).
      We report that P(i) at concentrations reached in exercising skeletal muscle (3-30
      mM) produced a dose-dependent stimulation of ryanodine binding to skeletal muscle
      SR. Ryanodine binding was increased by 84% in the presence of 30 mM P(i) with
      half-maximal stimulation at 4 mM P(i). In contrast to its effect on skeletal
      muscle SR, ryanodine binding to cardiac muscle SR was not stimulated by P(i) (3
      30 mM). Stimulation of ryanodine binding to skeletal muscle SR was maximal in the
      presence of micromolar Ca2+ and was associated with an increased affinity of the
      RyR for ryanodine (Kd = 204 nM in the absence, versus 107 nM in the presence of
      10 mM P(i)). P(i) (10 mM) also increased the rate of Ca2+ release from 45Ca(2+)
      filled skeletal muscle SR vesicles by 50% in the presence of micromolar Ca2+.
      Conversely, arsenate and sulfate (10 mM) had no effect on either ryanodine
      binding or Ca(2+)-induced Ca2+ release, demonstrating the specificity of the P(i)
      effect. Single-channel recordings of purified skeletal muscle SR RyR incorporated
      into planar lipid bilayers showed that addition of 10 mM P(i) to the cis chamber
      increased the open probability of the channel by 91%. These results demonstrate
      that concentrations of P(i) which occur in vivo during exercise significantly
      stimulate the in vitro activity of the skeletal muscle RyR Ca2+ release channel.

PMID- 8276795
TI  - Construction, expression, and activity of a bivalent bispecific single-chain
      antibody.
AB  - This report describes the design, construction, and expression of a bivalent
      bispecific single-chain antibody (SCA) protein in Escherichia coli. The
      bispecificity of the bivalent protein was based on two previously constructed
      monovalent single-chain antibody molecules possessing distinct specificities, SCA
      4-4-20 (anti-fluorescein) and SCA 04-01 (anti-single-stranded DNA). A flexible
      linker, modeled after a secreted fungal cellulase protein, was incorporated as
      the interdomain linker covalently joining the two active sites. Bivalent
      bispecific SCA protein that accumulated in bacteria as insoluble inclusion bodies
      was harvested, denatured, refolded, and affinity-purified in vitro. Affinity
      purified bivalent bispecific SCA showed nearly identical ligand binding
      properties at each site relative to the individual monovalent single-chain
      antibody prototype molecules. In both solid and solution phase binding assays,
      the bivalent bispecific single-chain antibody simultaneously bound both ligands
      (fluorescein and (dT)6). Construction of a model bivalent bispecific molecule
      provides a foundation for future assembly of similar molecules designed to
      identify parameters involved in enhanced binding of antibodies due to avidity and
      dual specificity.

PMID- 8276796
TI  - Vacuolar ATPase activity is required for endosomal carrier vesicle formation.
AB  - A proton pump, the vacuolar ATPase, is known to generate the acidic lumenal
      environment of endosomes and lysosomes. We have investigated the role of the
      vacuolar ATPase in endocytic membrane traffic by combining electron microscopy in
      vivo with a cell-free assay that reconstitutes endosome fusion in vitro. Our
      observations show that inactivation of this proton pump with bafilomycin A1 has
      no significant effects on internalization or recycling back to the plasma
      membrane. However, early endosomes become highly tubular and endocytosed markers
      do not appear in late endosomes. Our data strongly suggest that, upon
      inactivation of the proton pump, the formation of a vesicular intermediate
      between early and late endosomes, which we term endosomal carrier vesicle, is
      impaired.

PMID- 8276797
TI  - A proximal promoter element in the hamster desmin upstream regulatory region is
      responsible for activation by myogenic determination factors.
AB  - The muscle-specific intermediate filament protein desmin is up-regulated during
      skeletal muscle differentiation. When myoblasts leave the cell cycle and fusion
      into multinucleated myotubes starts, genes associated with myogenesis become
      activated. The activation is believed to be mediated by the muscle-specific
      determination factors. We present evidence that both MyoD and myogenin are able
      to activate the transcription of the hamster desmin gene. A proximal promoter
      fragment of 89 base pairs is sufficient for this transactivation process. The
      single E-box in this region is essential for desmin promoter activity in mouse C2
      skeletal muscle cells and upon co-transfection of a myogenin expression vector
      also in human primary fibroblasts. Mutation of this MyoD binding site abrogates
      desmin transcription, and transactivation of the promoter no longer occurs. By
      using gel electrophoretic mobility shift assays, we were able to demonstrate that
      nuclear proteins from C2 muscle cells and myogenin/E12 glutathione S-transferase
      fusion proteins are able to bind to the functional E-box consensus sequence. A
      second E-box, situated in a more upstream regulatory region, which also binds to
      purified Helix-Loop-Helix proteins in vitro is only moderately affected by site
      directed in vitro mutagenesis.

PMID- 8276798
TI  - Binding of recombinant fibrinogen mutants to platelets.
AB  - Platelet aggregation is mediated by the interaction of fibrinogen with platelet
      membrane glycoprotein IIb-IIIa, a member of the integrin family (integrin alpha
      IIb beta 3). Three different binding sites on fibrinogen for IIb-IIIa have been
      proposed, two RGD-containing sequences in the alpha chain and one dodecapeptide
      sequence at the carboxyl terminus of the gamma chain. However, recent evidence
      shows that mutations in either of the alpha chain sequences have no effect on
      platelet aggregation, whereas the substitution of a variant gamma chain (gamma')
      for the gamma chain results in a major reduction in platelet aggregation
      activity. The present investigation demonstrates that the gamma' chain shows
      decreased binding to IIb-IIIa as measured by direct binding experiments. In
      addition, adhesion studies indicate that the binding of both stimulated and
      unstimulated platelets to immobilized fibrinogens is mediated primarily through
      the gamma chain carboxyl terminus. Furthermore, a peptide corresponding to the
      carboxyl terminus of the gamma chain inhibits fibrinogen binding and platelet
      adhesion, whereas a peptide corresponding to the carboxyl terminus of the gamma'
      chain is significantly less inhibitory. These data show that the defective
      platelet aggregation activity of the fibrinogen gamma' chain is due to decreased
      binding to platelet glycoprotein IIb-IIIa.

PMID- 8276799
TI  - Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly
      expressed in leukocytes.
AB  - Several chemotactic agonists including interleukin-8 (IL-8) and related cytokines
      have been shown to activate and attract leukocytes via seven-transmembrane
      domain, GTP-binding protein-coupled receptors. A cDNA clone, LESTR, encoding a
      protein of 352 amino acids, corresponding to a novel receptor of this type, was
      isolated from a human blood monocyte cDNA library. The sequence of the deduced
      protein, LESTR (leukocyte-derived seven-transmembrane domain receptor), has 92.6%
      identity with that of a recently reported bovine neuropeptide Y (NPY) receptor,
      boLCR1 (Rimland, J., Xin, W., Sweetnam, P., Saijoh, K., Nestler, E. J., and
      Duman, R. S. (1991) Mol. Pharmacol. 40, 869-875). LESTR, however, is more similar
      (> 34%) to the IL-8 receptors, IL-8R1 and IL-8R2, than to several NPY receptors
      of different origin (< 20%). In the monocyte library, LESTR cDNA fragments were
      about 20 times as frequent as cDNA coding for IL-8R1 and IL-8R2, and much higher
      levels of LESTR- than IL-8R-specific mRNA were found in human blood neutrophils
      and lymphocytes. LESTR transcripts, by contrast, were low or undetectable in
      several neuroblastoma cell lines that are widely used to study NPY functions.
      Transfected cells expressing high levels of LESTR mRNA did not bind radiolabeled
      NPY, IL-8, NAP-2, GRO alpha, PF4, IP10, MCP-1, MCP-3, MIP-1 alpha, HC14, I309,
      RANTES, C3a, or LTB4. NPY also failed to bind to neutrophils, monocytes, and
      lymphocytes, to elicit responses in vitro such as Ca2+ changes, shape change,
      chemotaxis, enzyme release, and the respiratory burst, and to induce leukocyte
      accumulation upon injection in rats and rabbits. Although the ligand for LESTR
      could not be identified among a large number of chemotactic cytokines, the high
      expression in white blood cells and the marked sequence relation to IL-8R1 and IL
      8R2 suggest that LESTR may function in the activation of inflammatory cells.

PMID- 8276800
TI  - PIM1 encodes a mitochondrial ATP-dependent protease that is required for
      mitochondrial function in the yeast Saccharomyces cerevisiae.
AB  - The PIM1 nuclear gene in the yeast Saccharomyces cerevisiae encodes a
      mitochondrial ATP-dependent protease that exhibits over 30% identity with ATP
      dependent protease La from Escherichia coli, Lon from Bacillus brevis, and one
      from Myxococcus xanthus. In addition, Pim1 is 1133 amino acids long and has a
      putative mitochondrial import signal in the N-terminal region. Enzymatic
      comparisons of normal PIM1+ and deficient pim1-delta strains revealed that the
      ATP-dependent protease is located within the mitochondrial matrix. The pim1-delta
      strains are unable to utilize nonfermentable substrates as the sole carbon source
      and are unable to maintain functional mitochondrial DNA, indicating that the Pim1
      protease is required for mitochondrial function. PIM1 mRNA is constitutively
      expressed but is increased after thermal stress, suggesting that Pim1 may play a
      role in the heat shock response.

PMID- 8276801
TI  - Deamidation and isoaspartate formation during in vitro aging of recombinant
      tissue plasminogen activator.
AB  - When incubated at pH 7.3, 37 degrees C, human recombinant tissue plasminogen
      activator accumulated 0.77 mol of isoaspartate per mol of plasminogen activator
      over a 14-day period. Isoaspartate was detected by enzymatic transfer of 3H
      labeled methyl groups from S-adenosyl-L-methionine in a reaction catalyzed by
      protein L-isoaspartyl methyltransferase. Analysis of tryptic peptides derived
      from aged plasminogen activator revealed that the two major sites of isoaspartate
      accumulation resulted from deamidation of Asn58 in the sequence -FNGG- and Asn177
      in the sequence -GNSD-. Significant levels of isoaspartate also accumulated via
      deamidation of Asn37 in the sequence -CNSG-. All three sites occur in sequences
      predicted from studies with synthetic peptide to be unstable. All three sites
      appear to be on the surface of the protein, and all three occur in regions of the
      protein predicted to have higher than average chain mobility. These findings add
      support to the idea that sequence and flexibility play major roles in determining
      susceptibility to deamidation and peptide bond isomerization at Asn and Asp sites
      under mild conditions. These studies also illustrate the utility of enzymatic
      methylation for characterizing sites of deamidation in a large protein that
      contains numerous disulfide bonds and several sites of glycosylation.

PMID- 8276802
TI  - Differential cytokine regulation of type I and type VII collagen gene expression
      in cultured human dermal fibroblasts.
AB  - Type VII collagen is the major component of anchoring fibrils in the cutaneous
      basement membrane zone. In this study, we have examined the effects of various
      cytokines on the expression of types I and VII collagen genes in dermal
      fibroblasts in culture. The pro-inflammatory cytokines, interleukin-1 alpha (IL-1
      alpha), interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha),
      and leukoregulin (LR) strongly elevated (approximately 5-9-fold) type VII
      collagen mRNA levels, as measured by Northern blot hybridizations. These effects
      were also observed at the protein level by indirect immunofluorescence using a
      monoclonal antibody specific for type VII collagen. By contrast, IL-1 beta had
      only a slight stimulatory effect (approximately 2-fold) on type I collagen gene
      expression, while TNF-alpha and LR markedly reduced type I collagen mRNA steady
      state levels. Interestingly, IL-1, TNF-alpha and LR had additive effects with
      transforming growth factor-beta (TGF-beta) on type VII collagen gene expression,
      whereas they counteracted the up-regulatory effect of TGF-beta on type I collagen
      gene expression. Thus, our data indicate that the modulation of type I and type
      VII collagen gene expression by cytokines involves different regulatory pathways.

PMID- 8276803
TI  - Importance of the unique cationic residues arginine 12 and lysine 49 in the
      activity of the cardiotonic polypeptide anthopleurin B.
AB  - Sea anemone toxins are potentially important tools for understanding the
      pharmacology of voltage-sensitive sodium channels. We have previously described a
      bacterial expression system capable of producing large amounts of one such toxin,
      anthopleurin B (ApB), which delays channel repolarization (Gallagher, M. J., and
      Blumenthal K. M. (1992) J. Biol. Chem. 267, 13958-13963). It has been suggested
      that cationic residues are a major determinant of anemone toxin binding. In this
      paper, we describe characterization of three mutants at each of two unique
      cationic sites of ApB, Arg-12 and Lys-49. The activities of all mutants on
      cardiac and neuronal sodium channels have been compared with that of wild-type
      ApB. Mutation of Lys-49 has relatively minor effects on toxicity, whereas the
      mutant R12A, but not R12S or R12K, is severely impaired. These results indicate
      that cationic residues per se are not absolutely required at either position, but
      that polar side chains at position 12 contribute significantly to binding
      affinity. Furthermore, Arg-12 appears to be involved in the toxin's ability to
      discriminate between neuronal and cardiac sodium channels.

PMID- 8276804
TI  - The intracellular tyrosine kinase domain of the epidermal growth factor receptor
      undergoes a conformational change upon autophosphorylation.
AB  - The intracellular portion of the epidermal growth factor receptor consists of a
      tyrosine kinase domain of approximately 290 amino acids and a COOH-terminal
      regulatory domain of approximately 230 amino acids that contains five sites of
      autophosphorylation. The effect of autophosphorylation on the conformation of the
      intracellular domain has been analyzed using gel filtration. Both phosphorylated
      and dephosphorylated forms of the intracellular domain exist as monomers and as
      dimers and appear to have an extended conformation. The Stokes' radii of
      phosphorylated monomers and dimers were larger than those of the dephosphorylated
      forms, indicating that the dephosphorylated form is more compact. These results
      indicate that a significant conformational change occurs in the intracellular
      portion of the epidermal growth factor receptor upon tyrosine
      autophosphorylation.

PMID- 8276805
TI  - Interaction of 70-kDA heat shock cognate protein with peptides and myo-inositol
      monophosphatase.
AB  - Fluorescence techniques have been used to investigate the interaction of bovine
      70-kDa heat shock cognate protein (Hsc 70) with small molecular weight peptides
      and myo-inositol monophosphatase. The emission properties of Hsc 70 remain
      invariant upon addition of ATP. The results of steady-state fluorescence indicate
      that the tryptophan residues of Hsc 70 are exposed to the rapidly relaxing
      aqueous solvent. Binding of residues 1-20 of ribonuclease A (RNase S-peptide) to
      Hsc 70 causes protein fluorescence quenching which was used to determine a
      dissociation constant Kd = 2.7 microM for the binary Hsc 70.RNase S-peptide
      complex. The octapeptide corresponding to the NH2-terminal portion of sickle cell
      hemoglobin recognizes Hsc 70 and binds with a Kd = 9.3 microM. Binding of RNase S
      peptide to Hsc 70 produces a small enhancement of ATPase activity. Unfolded myo
      inositol monophosphatase, tagged with the fluorescent probe 5-[2-(2
      iodoacetamido)ethylamino]-1-naphthalenesulfonic acid, recognizes Hsc 70; the
      formation of a stable complex was detected by steady-state emission anisotropy
      measurements. The rate and extent of recovery of catalytic activity of unfolded
      myo-inositol monophosphatase is not influenced by Hsc 70. It is suggested that
      interaction of Hsc 70 with unfolded proteins in the cell may be able to delay the
      formation of misfolded structures.

PMID- 8276806
TI  - Molecular cloning of rat liver sulfite oxidase. Expression of a eukaryotic Mo
      pterin-containing enzyme in Escherichia coli.
AB  - The cDNA encoding sulfite oxidase has been cloned from a rat liver cDNA library.
      The gene contains a single open reading frame of 1464 nucleotides encoding a
      protein of 488 amino acids. The deduced amino acid sequence contains a 22-residue
      amino-terminal presequence that may serve as a mitochondrial targeting signal.
      The amino acid sequence deduced from the cDNA shows significant similarity to
      those of sulfite oxidase from chicken liver and nitrate reductases from algal,
      fungal, and plant sources. Two cysteine residues are conserved in all of these
      proteins, and it is proposed that one or both of these cysteines serve as ligands
      to molybdenum. The gene has been expressed in Escherichia coli to a level
      equivalent to that observed in rat liver. The recombinant enzyme has been found
      to contain the molybdopterin form of the molybdenum cofactor and is active as
      determined by the sulfite dependent reduction of cytochrome c.

PMID- 8276807
TI  - Identification of conserved amino acids in the human granulocyte-macrophage
      colony-stimulating factor receptor alpha subunit critical for function. Evidence
      for formation of a heterodimeric receptor complex prior to ligand binding.
AB  - A superfamily of growth factor and cytokine receptors has recently been
      identified, which is characterized by four spatially conserved cysteine residues,
      a tryptophan-serine motif (WSXWS) in the extracellular domain, and a proline-rich
      cytoplasmic domain. The high affinity human granulocyte-macrophage colony
      stimulating factor (GM-CSF) receptor (hGM-CSFR) consists of two subunits, alpha
      (hGM-CSFR alpha) and beta (hGM-CSFR beta), both of which are members of the
      receptor superfamily. In this study, we prepared mutations in conserved amino
      acids of the receptor subunit necessary for GM-CSF binding (hGM-CSFR alpha) and
      analyzed mutant receptors for low affinity binding, internalization, and high
      affinity binding when complexed with the beta subunit. Mutations in the
      cytoplasmic domain did not affect GM-CSF binding or receptor internalization.
      Mutation of a single conserved serine residue within the WSXWS motif diminishes
      cell surface receptor expression but not ligand binding. Mutation of either the
      second or third conserved cysteine residue of hGM-CSFR alpha resulted in complete
      loss of low affinity binding; however, co-expression of the cysteine 2 mutant
      with hGM-CSFR beta yielded a high affinity receptor complex. Since neither the
      cysteine 2 mutant nor the beta subunit can bind ligand alone, this result
      suggests that hGM-CSFR alpha and hGM-CSFR beta exist in a preformed heterodimeric
      protein complex on the plasma membrane.

PMID- 8276808
TI  - Identification of fatty acid hydroperoxide cofactors in the cytochrome P450
      mediated oxidation of estrogens to quinone metabolites. Role and balance of lipid
      peroxides during estrogen-induced carcinogenesis.
AB  - Lipid hydroperoxide-supported metabolic redox cycling between diethylstilbestrol
      (DES) or catechol-estrogens and their corresponding quinones has been postulated
      previously to play a role in estrogen-induced toxicity and carcinogenesis. As
      part of an examination of this postulate, we investigated (a) the effectiveness
      of various lipid hydroperoxides as oxidants in microsome-mediated quinone
      formation, and (b) the dependence of DES oxidation to quinone on lipid
      hydroperoxide levels in liver and kidney of hamsters. Kinetic analyses of the
      lipid hydroperoxide-mediated conversion of DES to DES quinone revealed that of
      the peroxides tested (9Z,11E,13(S))-13-hydroperoxyoctadecadien-1-oic acid was the
      most powerful oxidant (Vmax = 10.5 nmol min-1; Km = 21.3 microM) followed by
      (5(S),6E,8Z,11Z,14Z)-5-hydroperoxyeicosatetra en-1-oic acid (Vmax = 1.0 nmol min
      1; Km 10.0 microM). The other pure fatty acid hydroperoxide isomers or mixtures
      had a lower affinity for the enzyme (Km values ranging from 23.1 to 130 microM)
      and/or lower maximal velocity (Vmax values ranging from 0.2 to 7.0 nmol min-1).
      Levels of Z,Z-dienestrol, which arises from spontaneous rearrangement of DES
      quinone, were not affected in liver of hamsters treated with estradiol implants
      for 9 days and an injection of 20 mg/kg DES but increased in kidney by 120% over
      levels observed in animals without implants (5.5 and 12.1 nmol/g of wet tissue,
      respectively). Z,Z-Dienestrol concentrations correlated directly with lipid
      hydroperoxide concentrations in liver and kidney of control and estradiol-treated
      hamsters. The increased conversion of DES to quinone in kidney compared with that
      in liver was catalyzed by comparable activities of cytochrome P450 IA, the enzyme
      family catalyzing this oxidation. These results demonstrated that the oxidation
      of DES to quinone was directly dependent on the lipid hydroperoxide levels in the
      organ of metabolic conversion in addition to the enzyme activity catalyzing this
      reaction. The elevated lipid hydroperoxide levels in kidney of estrogen-treated
      hamsters indicate enhanced estrogen quinone formation and therefore enhanced
      generation of free radicals by metabolic redox cycling of estrogens in this organ
      prior to the appearance of malignancy.

PMID- 8276809
TI  - Direct activation of the phosphatidylinositol 3'-kinase by the insulin receptor.
AB  - We have previously shown that phosphatidylinositol (PtdIns) 3'-kinase is
      activated by the binding of proteins or peptides containing the phosphorylated
      motif Y(P)XXM. In the present study, we examine interactions between PtdIns 3'
      kinase and the human insulin receptor, which contains a C-terminal
      phosphorylation site in the sequence Y1322THM. Partially purified insulin
      receptors bound tightly to bacterial fusion proteins containing the N- or C
      terminal SH2 domains from PtdIns 3'-kinase regulatory subunit (p85). In contrast,
      a mutant insulin receptor, truncated by 43 amino acids at the C terminus (IR
      delta CT), bound poorly to the SH2 domains; these mutant receptors have normal
      kinase activity but lack the Y1322THM motif. Similarly, incubation with wild-type
      receptors increased the activity of immunopurified PtdIns 3'-kinase, whereas
      incubation with IR delta CT receptors did not affect PtdIns 3'-kinase activity.
      Activation of PtdIns 3'-kinase by the wild-type receptor was mimicked by a
      tyrosyl phosphopeptide derived from the insulin receptor C terminus and
      containing the Y1322THM motif; non-phosphorylated peptide did not affect
      activity. Thus, the insulin receptor C terminus activates PtdIns 3'-kinase in
      vitro by binding to the SH2 domains of the 85-kDa regulatory subunit. These data
      support the hypothesis that binding of tyrosyl-phosphorylated receptors to p85
      SH2 domains is a general mechanism for PtdIns 3'-kinase activation, and they
      suggest that direct interactions between the insulin receptor and PtdIns 3'
      kinase may provide an alternative pathway for the activation of this enzyme by
      insulin.

PMID- 8276810
TI  - Catechol-O-methyltransferase-catalyzed rapid O-methylation of mutagenic
      flavonoids. Metabolic inactivation as a possible reason for their lack of
      carcinogenicity in vivo.
AB  - Quercetin is highly mutagenic in vitro, yet is not carcinogenic when administered
      chronically at large doses to rodents for 12 months. We hypothesized that
      catechol-O-methyltransferase-catalyzed O-methylation of quercetin and other
      mutagenic catechol-containing flavonoids may provide an efficient inactivation in
      vivo and may therefore prevent tumor induction by these flavonoids. After one
      intraperitoneal administration of 50 mg/kg quercetin to hamsters, a urinary ether
      extract contained 2% quercetin and 97% 3'-O-methylquercetin. When the urine was
      treated first with beta-glucuronidase and sulfatase, 13% quercetin and 87% 3'-O
      methylquercetin were recovered. Quercetin was rapidly O-methylated by either
      porcine liver or hamster kidney catechol-O-methyltransferase, with Km values of
      6.1 and 6.9 microM and Vmax values of 14,870 and 200 pmol/mg of protein/min,
      respectively. S-Adenosyl-L-homocysteine exhibited a potent feedback inhibition of
      the catechol-O-methyltransferase-catalyzed O-methylation of quercetin by a
      competitive mechanism with respect to S-adenosyl-L-methionine and by a
      competitive plus noncompetitive mechanism with respect to the substrate. A
      comparison of the O-methylation rates and kinetic characteristics (Km, Vmax, and
      Vmax/Km) demonstrated that rates of O-methylation of quercetin and fisetin were
      up to three orders of magnitude higher than those of catechol estrogens and
      catecholamines. In conclusion, the rapid metabolic inactivation of mutagenic
      flavonoids catalyzed by catechol-O-methyltransferase may be a major reason for
      the lack of their carcinogenic activities in vivo.

PMID- 8276811
TI  - Biosynthesis of heparan sulfate on beta-D-xylosides depends on aglycone
      structure.
AB  - We have reported that 3-estradiol-beta-D-xyloside primes heparan sulfate
      synthesis in Chinese hamster ovary cells and that the proportion of heparan
      sulfate made rises with increasing concentration of xyloside (Lugemwa, F.N. and
      Esko, J.D. (1991) J. Biol. Chem. 266, 6674-6677). Using estradiol as a guide, we
      varied the structure of the aglycone and showed that beta-D-xylosides containing
      two fused aromatic rings efficiently prime heparan sulfate. Thus, 2-naphthol-beta
      D-xyloside primed heparan sulfate at low dose (< or = 10 microM) and the
      proportion of heparan sulfate increased with concentration (up to 50% of total
      glycosaminoglycan). Various ring additions and heterocyclic ring substitutions
      altered the efficiency of heparan sulfate priming, but had no effect on the
      overall level of glycosaminoglycan synthesis. Replacement of the bridging oxygen
      with sulfur (2-naphthalenethiol-beta-D-xyloside) increased the efficiency of
      heparan sulfate priming. Priming of heparan sulfate correlated with
      hydrophobicity of the xyloside, but several exceptions suggested that the
      chemical structure of the aglycone played an equally important role.
      Interestingly, the heparan sulfate chains generated on 2-naphthol-beta-D-xyloside
      showed a 2-fold decrease in the proportion of disaccharides containing 6-O
      sulfate groups and a striking diminution in non-sulfated iduronic acid containing
      disaccharides compared to the chains attached to cellular proteoglycans. Thus,
      both the type of glycosaminoglycan made on a xyloside and its fine structure
      depends on the aglycone.

PMID- 8276812
TI  - Isolation and characterization of a nerve growth factor-regulated Fos kinase from
      PC12 cells.
AB  - Nerve growth factor (NGF) treatment of PC12 cells activates a protein kinase that
      phosphorylates c-Fos protein at a site near its C terminus, as well as a peptide
      corresponding to a C-terminal region of c-Fos (Taylor, L. K., Marshak, D. R., and
      Landreth, G. E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 368-372). This
      serine/threonine kinase, termed Fos kinase, has been purified > 24,000-fold
      through five column steps to near homogeneity and is shown to be a 37-kDa protein
      as determined by SDS-polyacrylamide gel electrophoresis (PAGE) with a pI = 6.0.
      Fos kinase is distinguishable from previously characterized NGF-regulated kinases
      by its chromatographic behavior, its response to specific kinase inhibitors, and
      its substrate specificity. The concentration of NGF required to activate Fos
      kinase is consistent with signaling from the high affinity NGF receptor. Fos
      kinase phosphorylates c-Fos at its C terminus as indicated by competitive
      inhibition with a peptide corresponding to C-terminal phosphorylation sites and
      lack of phosphorylation of a C-terminal deletion mutant of c-Fos.
      Hyperphosphorylation of c-Fos in vivo, as detected by reduced electrophoretic
      mobility of c-Fos, is induced by the same ligands which activate Fos kinase.
      Moreover, Fos kinase phosphorylation of c-Fos in vitro results in a similar
      electrophoretic mobility shift, demonstrating that Fos kinase may be responsible
      for growth factor-stimulated alterations in mobility on SDS-PAGE and
      phosphorylation of this transcription factor. The ability of this unique growth
      factor-responsive kinase to phosphorylate c-Fos at its C terminus, a region
      essential for the transrepressive properties of c-Fos, suggests that Fos kinase
      may play a role in the regulation of the transcriptional repressive activity of c
      Fos.

PMID- 8276813
TI  - Hysteretic inhibition of the bovine heart mitochondrial F1-ATPase is due to
      saturation of noncatalytic sites with ADP which blocks activation of the enzyme
      by ATP.
AB  - Prior incubation of the bovine heart mitochondrial F1-ATPase depleted of
      endogenous nucleotides (nd-MF1) with saturating ADP in the presence or absence of
      Mg2+ induces inhibition of hydrolysis of 2 mM ATP or ITP. After incubation of nd
      MF1 with free ADP, inhibition develops hysteretically which is characterized by
      an uninhibited initial rate which decelerates to an inhibited, steady-state rate.
      When prior incubation of nd-MF1 is performed with ADP in the presence of Mg2+,
      the enzyme is partially inhibited when diluted into assay medium and more
      extensive inhibition develops hysteretically during turnover. Correlation of
      binding of [14C]ADP, in the presence or absence of Mg2+, with the extent of
      hysteretic inhibition induced suggests that maximal inhibition occurs when at
      least two noncatalytic sites are filled with ADP. Hysteretic inhibition is also
      induced by prior incubation of the enzyme with 2-N3-ADP. Prior incubation of nd
      MF1 with increasing concentrations of 2-N3-[beta-32P]ADP, in the presence or
      absence of Mg2+, increases the extent of induced inhibition which correlates with
      increasing derivatization of tyrosine beta 368 following irradiation of loaded
      enzyme. This demonstrates that binding of ADP to noncatalytic sites is, in part,
      responsible for induction of hysteretic inhibition. After inducing inhibition by
      prior incubation with ADP, the steady-state kinetic behavior of nd-MF1 differs
      from that of uninhibited enzyme. Lineweaver-Burk plots of steady-state rates of
      inhibited enzyme as a function of ATP concentration are linear rather than
      biphasic which is observed for uninhibited enzyme. The composite results suggest
      that prior saturation of noncatalytic sites of nd-MF1 with ADP prevents
      activation of the enzyme by blocking the binding of ATP to these sites which is
      necessary to promote dissociation of inhibitory MgADP from a catalytic site.

PMID- 8276814
TI  - Domains of the human neutrophil N-formyl peptide receptor involved in G protein
      coupling. Mapping with receptor-derived peptides.
AB  - Chemotactic signaling by the human neutrophil N-formyl peptide receptor requires
      its association with heterotrimeric G protein. Synthetic peptides and a fusion
      protein derived from the intracellular regions of the receptor were used to
      identify sites which interact with G protein. A peptide derived from the second
      intracellular loop (C12R), and peptides (F15R and S22L) and a fusion protein
      derived from the receptor's carboxyl terminus inhibited binding of anti-Gi alpha
      antibody (R16,17) to Gi alpha in a competitive enzyme-linked immunoassay, and
      antagonized pertussis-toxin catalyzed ADP-ribosylation of Gi alpha. C12R also
      inhibited G protein-dependent, high affinity ligand binding to the receptor and
      physical coupling of receptor to G protein. In contrast, a peptide consisting of
      the entire third loop of the N-formyl peptide receptor was totally inactive in
      these assays. Collectively, these data suggest that the second intracellular loop
      and the carboxyl-terminal tail are important for effective N-formyl peptide
      receptor/G protein coupling, but that the third intracellular loop is less
      important in coupling, unlike previous findings with other G protein-coupled
      receptor systems. The chemoattractant receptor family may rely on different
      structural determinants to interact with GTP-binding proteins.

PMID- 8276815
TI  - Expression of constitutively active Gs alpha-subunits in GH3 pituitary cells
      stimulates prolactin promoter activity.
AB  - Although G protein alpha subunits are known to regulate such cellular functions
      as growth and enzymatic activity, the ability of these proteins to regulate
      target gene expression has not yet been directly investigated. Transient
      expression in GH3 pituitary cells of a target rat prolactin promoter
      chloramphenicol acetyltransferase construct, (-1957)PRL-CAT, was increased by
      coexpressed constitutively active alpha s mutant Q227L-alpha s but not by wild
      type alpha s. Thus activated alpha s but not basal state alpha s can stimulate
      prolactin promoter activity. Q227L-alpha s also stimulated expression of
      construct (-187)PRL-CAT, showing that only the proximal prolactin promoter region
      is required for a response to activated alpha s. The promoter specificity of the
      transcriptional influence of activated alpha s was demonstrated by the inability
      of either Q227L-alpha s or wild-type alpha s to stimulate expression of control
      target constructs containing either the rat growth hormone promoter or the
      thymidine kinase promoter. Previous studies have shown that the most proximal
      prolactin promoter binding site for the pituitary-specific transcription factor
      pit-1, site 1P, can act as an independent response element for either thyrotropin
      releasing hormone or Ca2+. Two copies of site 1P conferred upon a heterologous
      metallothionein promoter a response to Q227L-alpha s. This implies that site 1P
      can also serve as an independent response element for alpha s and suggests that
      pit-1 may be a mediator of the cellular regulation by alpha s of the prolactin
      promoter.

PMID- 8276816
TI  - Identification of functional elements and reconstitution of the alpha 1(VI)
      collagen promoter.
AB  - To gain insight into the regulatory mechanisms of collagen VI synthesis we have
      characterized the cis-acting elements of the chicken alpha 1(VI) collagen
      promoter. Footprinting experiments with nuclear extracts from chicken embryos
      revealed three distinct elements, designated A, B, and C, that were protected
      from DNase I digestion. The nuclear proteins that interact with the three sites
      were identified by gel retardation assays in combination with the use of various
      oligonucleotide competitors as well as specific antibodies raised against well
      characterized transcription factors. Site A was found to be a target for
      transcriptional activator AP1, whereas sites B and C were shown to be recognized
      each by two distinct nuclear proteins which belong to the Sp1 multigene family.
      To address the question whether the three sites alone are able to direct
      transcription, a minipromoter construct was created in which the sequences of
      sites A, B, and C were placed in front of a reporter gene. After transfection
      into chicken fibroblasts, this construct exhibited a high relative promoter
      activity when compared to a large genomic fragment containing the basic alpha
      1(VI) collagen promoter. Thus, the three sites are sufficient to induce
      transcription of this gene.

PMID- 8276817
TI  - Structure and regulation of the mouse cardiac troponin I gene.
AB  - The gene coding for mouse cardiac troponin I (TnI) has been cloned and sequenced.
      The cardiac TnI gene contains 8 exons and has an exon-intron organization similar
      to the quail fast skeletal TnI gene except for the region of exons 1-3, which is
      highly divergent. Comparative analysis suggests that cardiac TnI exon 1
      corresponds to fast TnI exons 1 and 2 and that cardiac exon 3, which codes for
      most of the cardiac-specific amino-terminal extension and has no counterpart in
      the fast gene, evolved by exon insertion/deletion. The amino acid sequence of
      cardiac TnI exon 4 shows limited homology (36% identity) with fast TnI exon 4 but
      is remarkably similar (79% identity) to the corresponding sequence of slow TnI,
      possibly reflecting an isoform-specific TnC-binding site. The cardiac TnI gene is
      one of the very few contractile protein genes expressed exclusively in cardiac
      muscle. To identify the regulatory sequences responsible for the cardiac-specific
      expression of this gene we transfected cultured cardiac and skeletal muscle cells
      with fragments up to 4.0 kilobases of the 5'-flanking region linked to a reporter
      gene. Deletion analysis reveals four major regions in the 5'-flanking sequence, a
      minimal promoter region, which directs expression at low level in cardiac and
      skeletal muscle cells, and two upstream cardiac-specific positive regions
      separated by a negative region.

PMID- 8276818
TI  - Structure of two rat genes coding for closely related rolipram-sensitive cAMP
      phosphodiesterases. Multiple mRNA variants originate from alternative splicing
      and multiple start sites.
AB  - The products of two phosphodiesterase (PDE) genes (ratPDE3/IVd and ratPDE4/IVb)
      are present in the rat Sertoli cell in culture, and their expression is under the
      control of the gonadotropin follicle-stimulating hormone (Swinnen, J.V.,
      Tsikalas, K.E., and Conti, M. (1991) J. Biol. Chem. 266, 18370-18377). To
      understand the basis of the sequence heterogeneity found in the 5'-region of the
      different cDNAs thus far characterized, the structure of the coding region of
      these two cAMP PDE genes was investigated. Analysis of five ratPDE3/IVd and
      ratPDE4/IVb genomic clones showed that the coding region of these genes expressed
      in the Sertoli cell is divided into 11 exons distributed over 35-45 kilobases of
      genomic DNA. The intron/exon boundaries agreed, with some exceptions, with the
      established consensus sequences and were located in the same position in the
      coding region of the two genes. Also present were similarities to the exon
      composition of the Drosophila melanogaster "dunce" gene, the ancestor of these
      mammalian cAMP PDEs. Multiple AUG codons and short open reading frames were
      present at the 5'-untranslated end of the ratPDE4/IVb mRNA, but not in the
      ratPDE3 mRNA. By using polymerase chain reaction amplification or Northern
      analysis, it was determined that at least two forms of ratPDE3/IVd mRNA are
      present in rat Sertoli and FRTL-5 thyroid cells, but not in the brain. These mRNA
      variants are generated by inclusion or removal of an intron sequence that
      produces a frameshift affecting the position of the initiation AUG codon. Both
      mRNA species were efficiently translated into cAMP PDE proteins with different
      molecular masses in a transient transfection assay in COS cells. Polymerase chain
      reaction amplification demonstrated that heterogeneity of ratPDE4/IVb mRNAs was
      present in the same location as in the ratPDE3/IVd mRNA. Two ratPDE4/IVb mRNAs
      with different 5'-ends were expressed in Sertoli and FRTL-5 cells and in the
      brain. This heterogeneity is caused by the presence of an intron promoter that
      controls the transcription of this mRNA in Sertoli and FRTL-5 cells, but not in
      the brain. Upstream exons and additional promoters are probably present and
      necessary to generate the brain-specific mRNAs. These findings demonstrate that
      the cAMP-specific PDE genes have complex structure and that cAMP PDE proteins
      with different amino termini are derived from these genes.

PMID- 8276819
TI  - Inhibition of protein phosphatases activates P4 promoter of the human insulin
      like growth factor II gene through the specific promoter element.
AB  - To understand the transcriptional regulation of the human insulin-like growth
      factor II (IGF-II) gene, we examined the effects of okadaic acid, a potent in
      vitro inhibitor of protein phosphatases, on the activation of human IGF-II gene
      expression. Treatment of A-549 human lung adenocarcinoma cells with okadaic acid
      increased expression of the IGF-II mRNAs. Since the 4.8-kb mRNA is transcribed
      under the control of human IGF-II P4 promoter, we examined the P4 promoter
      element responsible for the okadaic acid-mediated transcriptional activation.
      Transfection of IGF-II P4 promoter-chloramphenicol acetyltransferase constructs
      demonstrated that the effects of okadaic acid on the induction of IGF-II gene
      expression are mediated through multiple promoter elements, including an Egr-1
      consensus element. We have also shown that okadaic acid induced the expression of
      the transcription factor Egr-1. Moreover, by using a GAL4-Egr-1 fusion protein,
      we have directly demonstrated that okadaic acid positively regulates Egr-1
      transcriptional activity in vivo. These results indicate that protein
      phosphatases play an important role in the transcriptional regulation of the IGF
      II.

PMID- 8276820
TI  - Adenophostins, newly discovered metabolites of Penicillium brevicompactum, act as
      potent agonists of the inositol 1,4,5-trisphosphate receptor.
AB  - Potent inositol 1,4,5-trisphosphate (IP3) receptor agonists, adenophostin A and
      B, were found from fungal products. In spite of the striking structural
      difference from IP3, adenophostins were found to inhibit [3H]IP3 binding more
      potently than IP3: the Ki values for adenophostin A and B were both calculated to
      be 0.18 nM, while that of IP3 was 15 nM. Adenophostins induced Ca2+ release both
      from cerebellar microsomes and from intracellular Ca2+ stores in permeabilized
      NG108-15 cells. Adenophostins at concentration as low as 1 nM produced a
      significant Ca2+ release from cerebellar microsomes, and their activities were
      100-fold more potent than IP3. In addition, heparin, an IP3 receptor antagonist,
      completely blocked the Ca2+ releasing activity of adenophostins. Adenophostins
      were resistant to phosphorylation and dephosphorylation by IP3-metabolizing
      enzymes, thereby providing a possible explanation for their prolonged activities.
      Adenophostin also bound to plasma membrane IP3 receptor with a high affinity and
      inhibited [3H]IP3 binding to jurkat human T-cell plasma membranes: the IC50 value
      for adenophostin A was 0.95 nM. Adenophostin may prove to be a powerful tool for
      investigating the physiological properties of IP3 and its receptor.

PMID- 8276821
TI  - Olfactory desensitization requires membrane targeting of receptor kinase mediated
      by beta gamma-subunits of heterotrimeric G proteins.
AB  - Olfaction is mediated by G protein-coupled receptors. In isolated rat olfactory
      cilia, odorants such as citralva stimulate a burst of cAMP, which peaks in 50 ms
      and returns almost to base-line level within 150 ms in the continuing presence of
      odorant. This desensitization is mediated by the cAMP dependent protein kinase
      and a specialized G protein-coupled receptor kinase originally termed beta ARK2
      (GRK3). In vitro experiments suggest that the prenylated beta gamma-subunits of
      heterotrimeric G proteins target the cytosolic beta ARK1 (GRK2) enzyme to its
      membrane bound receptor substrate by binding to sites in its carboxyl terminus.
      Here we demonstrate that odorants stimulate translocation of GRK3 from cytosol to
      membranes in isolated rat olfactory cilia. We introduced a glutathione S
      transferase-GRK3ct fusion protein, containing the carboxyl-terminal 222 amino
      acid residues of GRK3, which includes the beta gamma binding site, or a 28-amino
      acid peptide derived therefrom, into permeabilized cilia preparations. These
      reagents block odorant-mediated enzyme translocation and desensitization while
      markedly attenuating odorant-stimulated phosphorylation of olfactory proteins.
      These findings suggest that beta gamma-subunits may physiologically regulate a G
      protein-coupled receptor kinase and that enzyme translocation may be a general
      and required feature of the activity of some members of this enzyme family.

PMID- 8276822
TI  - Functional roles for the glutamines within the glutamine-rich region of the
      transcription factor sigma 54.
AB  - Single and multiple point mutations were introduced to change the 12 glutamine
      residues within a 37-amino acid region of sigma 54. Multiple changes are shown to
      be required in order to interfere significantly with the function of this protein
      which is associated with enhancer-dependent bacterial transcription. Mutation of
      the central 4 glutamines leads to the production of less m-RNA, caused by an
      inability to fully open the promoter start site. DNA binding, however, is normal.
      Mutation of 4 other adjacent glutamines causes the promoter start site to open
      more readily than wild type, although this enhanced opening is not accompanied by
      more mRNA. The enhanced DNA melting is not caused by enhanced promoter binding,
      as indicated by normal protection of the polymerase-bound promoter against
      dimethyl sulfate attack. The results suggest that multiple glutamines play a role
      in transducing the melting signal from the enhancer protein to the polymerase.

PMID- 8276823
TI  - Reengineering the specificity of a serine active-site enzyme. Two active-site
      mutations convert a hydrolase to a transferase.
AB  - Two residues are known to play important catalytic roles in fatty acyl-thioester
      hydrolase, thioesterase II: Ser-101, the site of a covalent acyl-enzyme
      intermediate, and His-237 which is within hydrogen bonding distance of Ser-101
      and facilitates catalysis by increasing the nucleophilicity of this residue. In
      this study we have examined the effect of mutations at these two residues on the
      ability of the enzyme to function as a hydrolase and, in the presence of a thiol
      acceptor, as an acyltransferase. In the hydrolase reaction kcat values for the
      wild-type, H237R, S101C, and S101C, H237R thioesterase enzymes were 0.11, <
      0.002, 0.10, and < 0.002 s-1, respectively, and at steady state, the proportion
      of each enzyme present as the covalent acyl-enzyme intermediate was 11, 91, 71,
      and 100%, respectively. In the acyltransferase reaction no activity could be
      detected for the wild-type or H237R enzymes but the specific activities of the
      S101C and S101C/H237R thioesterases were 170 and 1300 nmol/min/mg of protein,
      respectively. From this data we conclude the following: the wild-type enzyme
      functions exclusively as a hydrolase. The H237R mutant acts ineffectively as a
      hydrolase primarily because the deacylation reaction is drastically retarded. The
      S101C enzyme functions well as a hydrolase, even though the rate of deacylation
      is adversely affected, and this enzyme can also perform as an acyltransferase.
      Mutation of both catalytic residues leads to a complete loss of hydrolase
      activity and the S101C,H237R mutant functions as an effective acyltransferase
      exhibiting kcat values higher then those of the wild-type enzyme acting as a
      hydrolase. This study reveals that, with only two amino acid replacements, an
      enzyme capable of functioning exclusively as a hydrolase can be converted into an
      equally active enzyme performing solely as an acyltransferase.

PMID- 8276824
TI  - Mammalian ferrochelatase. Expression and characterization of normal and two human
      protoporphyric ferrochelatases.
AB  - Ferrochelatase (EC 4.99.1.1) catalyzes the terminal step in the heme biosynthetic
      pathway, the insertion of ferrous iron into protoporphyrin IX. Herein we report
      the expression, purification, and characterization of the mature processed form
      of human and mouse ferrochelatase in Escherichia coli JM109. Metal analysis of
      the recombinant normal human ferrochelatase reveals that there are approximately
      2 iron atoms/molecule of enzyme. This, along with the presence of spectral
      absorbance near 320 nm, is strongly suggestive that recombinant mammalian
      ferrochelatase as expressed in E. coli may contain an iron sulfur cluster. Two
      human protoporphyric ferrochelatases, F417S and M267I, were also expressed and
      characterized. The M267I mutant possesses the same Km and Vmax as the normal
      enzyme but exhibits increased thermolability when compared with normal human
      ferrochelatase. The F417S mutant has less than 2% of the normal activity. Since
      the Phe-->Ser substitution in this mutation is both chemically and structurally
      significant, three single amino acid substitutions (Lys, Tyr, and Trp) were
      engineered and characterized. None of these resulted in a protein with wild type
      activity. Additionally the carboxyl-terminal 10-amino acid segment, which
      contains Phe-417, from the yeast sequence was substituted, but this construct had
      no activity. Elimination of the carboxyl-terminal 30 amino acid residues (which
      include Phe-417) results in a protein the same length as the bacterial
      ferrochelatases, but it is an inactive enzyme.

PMID- 8276825
TI  - Regulation of 5-hydroxytryptamine2 (5-HT2) receptor expression in cultured rat
      aortic smooth muscle cells by SR 46349B, a selective 5-HT2 receptor antagonist.
AB  - Regulation of 5-hydroxytryptamine (5-HT2) receptor expression by SR 46349B, a
      potent and selective 5-HT2 receptor antagonist, was investigated in cultured rat
      aortic smooth muscle cells. Binding of [3H]SR 46349B to rat vascular smooth
      muscle cells was time-dependent, reversible, and saturable. [3H]SR 46349B bound
      to one class of specific binding sites with high affinity (KD = 1.3 +/- 0.3 nM;
      Bmax = 176 +/- 42 fmol/10(5) cells). Exposure of cells to a 1 microM
      concentration of the 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2
      aminopropane ((+/-)-DOI) or the antagonist ketanserin led to a significant
      decrease in 5-HT2 receptor density as measured by [3H]SR 46349B binding. In
      contrast, exposure of cells to 1 microM SR 46349B caused a marked increase in the
      maximal binding capacity of [3H]SR 46349B, with a maximal effect at 24 h (73%
      increase). The affinity constant was not affected by prior exposure to (+/-)-DOI,
      ketanserin, or SR 46349B. Furthermore, exposure of cells to 1 microM (+/-)-DOI or
      ketanserin produced, 48 h later, a decrease in the ability of (+/-)-DOI to
      stimulate phosphoinositide turnover in the cells, whereas treatment with SR
      46349B induced a significant stimulation of the 5-HT2 receptor-linked signal
      transduction. This effect occurred with no changes in the amount of 5-HT2
      receptor mRNAs as measured by quantitative polymerase chain reaction. These
      results indicate that SR 46349B increases 5-HT2 receptor binding and functions
      without altering steady-state 5-HT2 mRNA levels in cultured rat aortic smooth
      muscle cells.

PMID- 8276826
TI  - Identification of an intracellular tyrosine residue critical for muscarinic
      receptor-mediated stimulation of phosphatidylinositol hydrolysis.
AB  - Several lines of evidence suggest that the N-terminal portion of the third
      cytoplasmic loop (i3) of muscarinic and other G protein-coupled receptors is of
      pivotal importance for G protein recognition and activation. The present study
      was designed to identify specific amino acids within this domain required for
      muscarinic receptor-induced activation of G proteins mediating stimulation of
      phosphatidylinositol (PI) hydrolysis. Among the five mammalian muscarinic
      receptors (m1-m5), only the m1, m3, and m5 receptors are efficiently coupled to
      this second messenger pathway. Initially, we created a series of rat m3 receptor
      mutants in which short segments in the N terminus of the i3 loop were replaced
      with the corresponding m2 receptor sequences. The effect of these substitutions
      on m3 receptor-mediated stimulation of PI hydrolysis was studied in transiently
      transfected COS-7 cells. We found that a stretch of 4 amino acids (Arg252-Ile253
      Tyr254-Lys255) located at the beginning of the i3 domain of the m3 muscarinic
      receptor is critically involved in receptor-mediated stimulation of PI
      hydrolysis. Further mutational analysis of this 4-amino acid segment by single
      amino acid substitutions demonstrated that only Tyr254 is essential for efficient
      activation of the PI pathway. This tyrosine residue is conserved among all PI
      coupled muscarinic receptors as well as in many other biogenic amine and
      glycoprotein hormone receptors, suggesting that it may also play an important
      functional role in other G protein-coupled receptors.

PMID- 8276827
TI  - Lysine- and arginine-specific proteinases from Porphyromonas gingivalis.
      Isolation, characterization, and evidence for the existence of complexes with
      hemagglutinins.
AB  - Porphyromonas gingivalis contains many virulence factors that have been
      implicated as participants in the progression of periodontal disease. It has been
      shown to produce proteinases of "trypsin-like" specificity in a number of
      molecular forms, but previous work in our laboratory resulted in the purification
      of a major arginine-specific cysteine proteinase, gingipain, which contradicted
      this supposed specificity. In this study, separate proteinases with arginine and
      lysine specificity were isolated from a high molecular mass fraction of the P.
      gingivalis culture fluid. The arginine-specific enzyme was found, by amino acid
      sequencing studies, to be a high molecular mass form of gingipain, formed by the
      50-kDa gingipain noncovalently complexed with 44-kDa binding proteins,
      subsequently identified as hemagglutinins. The 60-kDa lysine-specific proteinase,
      referred to as Lys-gingipain, was also found to have one of these hemagglutinins
      complexed with it in the same manner. Lys-gingipain was found to be a cysteine
      proteinase with optimal activity and stability at pH 8.0-8.5 and was extensively
      characterized in terms of its specificity and activation characteristics. The
      proteinase-hemagglutinin complexes may be important in the uptake of hemin, a
      vital metabolite for P. gingivalis, via hemagglutination and subsequent hemolysis
      of erythrocytes.

PMID- 8276828
TI  - The Ca2+ affinity of the plasma membrane Ca2+ pump is controlled by alternative
      splicing.
AB  - The plasma membrane Ca2+ pump is a calmodulin-regulated P-type ATPase that is an
      essential element in controlling intracellular Ca2+ concentration. Studies on the
      gene structure of this pump have revealed an alternate splice option that changes
      the structure of the calmodulin-binding domain. This change in the structure of
      the enzyme results in a reduced calmodulin affinity. Tests of the enzyme's
      activity in the presence of a high calmodulin concentration, approximating that
      found inside living cells, show that this reduced calmodulin affinity causes a
      reduced apparent affinity of the enzyme for Ca2+. This shift in the Ca2+
      activation occurs in a Ca2+ concentration range crucial to cellular function and
      is probably the physiologically important consequence of the alternate splice.

PMID- 8276829
TI  - Active site mutants of Escherichia coli citrate synthase. Effects of mutations on
      catalytic and allosteric properties.
AB  - We report properties of five active site mutants of Escherichia coli citrate
      synthase, in which histidine 264, aspartate 362, and phenylalanine 383 were
      replaced by alanines, and arginines 387 and 407 by leucines. All mutants have
      much lower turnover numbers than wild type enzyme; the strongest effect was with
      the arginine 387 mutant, perhaps because the substrate, oxaloacetate, binds in a
      different orientation. The arginine 407 mutant has lost most of its ability to
      distinguish alpha-ketoglutarate, a competitive inhibitor, from oxaloacetate. The
      mutations of histidine 264 and aspartate 362 affect steady-state kinetics as
      would be anticipated from current models for citrate synthase catalysis, and
      resemble mutations of these residues, in pig heart and E. coli enzyme, reported
      by others. Mutations of residues 264, 362, and 383 also affect allosteric
      properties. With the phenylalanine 383 mutant, acetyl-CoA saturation is strongly
      sigmoid, even in the presence of the activator, KCl, implying a marked shift of
      the allosteric equilibrium toward the T state. The histidine 264 mutant appears
      to be shifted toward R state and shows weaker binding of the allosteric
      inhibitor, NADH; thus this mutation also affects the allosteric site, 25-30 A
      away.

PMID- 8276830
TI  - Mutagenesis of subunit delta from Escherichia coli F1F0-ATP synthase.
AB  - In Escherichia coli, the F1 sector of the F1F0-ATP synthase is connected to the
      membrane-embedded F0 sector by a narrow stalk, thought to be formed by subunits
      delta and b. Mutagenic analysis was used here to study the structure and function
      of subunit delta. First, random mutations in the protein were generated by
      bisulfite mutagenesis. Two single missense mutations causing impaired growth by
      oxidative phosphorylation were found, namely delta A149T and delta G150D. Both
      occur at the conserved C-terminal region, which has been suggested previously to
      be functionally important. Two techniques were applied to study the C-terminal
      region in greater detail. Cassette mutagenesis was used to randomly mutate the
      sequence from delta 145 to delta 167, and residues delta A149 and delta G150 were
      specifically mutated by site-directed mutagenesis to obtain multiple
      substitutions at each position. Fifteen of the residues between delta 145 and
      delta 167 were mutated. None was found to be absolutely essential for function.
      However, the properties of the mutants obtained, which included partial
      impairment of growth by oxidative phosphorylation, temperature sensitivity, and
      specific structural requirements at residues delta A149 and delta G150, confirmed
      that this region is important for enzyme function. Based on these studies, and on
      secondary and tertiary structure predictions, a model for subunit delta and its
      orientation in F1F0-ATP synthase is proposed.

PMID- 8276831
TI  - Defective energy coupling in delta-subunit mutants of Escherichia coli F1F0-ATP
      synthase.
AB  - Membrane vesicles from 13 strains carrying mutations in the C-terminal region of
      the delta-subunit of Escherichia coli F1F0-ATP synthase were characterized in
      respect to ATPase activity, ATP-driven proton-pumping, dicyclohexylcarbodiimide
      sensitivity of ATPase, and oxidative phosphorylation. The salient finding was
      that energy-coupling between F1 and F0 sectors of the enzyme is impaired by
      several of the mutations. The delta G150N mutant appeared completely uncoupled in
      vitro. The data emphasize the role of the C-terminal region of delta-subunit in
      integration of the proton conduction machinery in F0 with the three F1 catalytic
      sites. It is suggested that the C-terminal region of delta-subunit, speculatively
      located in the central region of the alpha 3 beta 3 hexagon, acts functionally at
      the interface between the helical domain of the stalk and the F1 subunits to
      relay conformational signals which alter the affinities of the catalytic sites
      for substrates and products.

PMID- 8276832
TI  - Phosphorylation selectively increases triiodothyronine receptor homodimer binding
      to DNA.
AB  - Thyroid hormone receptors (TRs) are ligand-regulated transcription factors that
      bind to thyroid hormone response elements (TREs) as monomers and homodimers, and
      as heterodimers with nuclear proteins such as TR auxiliary proteins and retinoid
      X receptors. Recently, bacterially expressed human TR beta-1 (hTR beta-1) was
      shown to be phosphorylated in vitro by HeLa cytosolic extract. However, little is
      known about the consequences of phosphorylation on the nature of TR complexes.
      Therefore, we studied the effect of phosphorylation on TR binding of TREs.
      Bacterially expressed hTR beta-1 was phosphorylated in vitro with ATP by HeLa
      cytosolic extract. The ratio of phosphoserine to phosphothreonine was
      approximately 5:1. We then analyzed phosphorylated hTR beta-1 binding to several
      TREs by electrophoretic mobility shift assay. Phosphorylated hTR beta-1 bound
      better as a homodimer to the TREs than hTR beta-1 incubated with preheated
      cytosolic extract. Alkaline phosphatase treatment of the phosphorylated hTR beta
      1 eliminated the enhanced homodimer binding to DNA. In contrast, phosphorylation
      did not affect TR/TR auxiliary protein or TR/retinoid X receptor heterodimer
      binding to DNA. Triiodothyronine decreased both phosphorylated and
      unphosphorylated hTR beta-1 homodimer binding to several TREs, and the addition
      of okadaic acid did not alter this triiodothyronine effect. These results
      indicate that phosphorylation, in addition to ligand binding, modulates TR dimer
      binding to TREs. As such, it is possible that phosphorylation may also
      participate in TR-mediated regulation of transcription.

PMID- 8276833
TI  - A single mutation in bacteriophage T4 DNA polymerase (A737V, tsL141) decreases
      its processivity as a polymerase and increases its processivity as a 3'-->5'
      exonuclease.
AB  - The bacteriophage T4 DNA polymerase mutant A737V (tsL141 and tsCB120) was
      originally characterized as temperature-sensitive for DNA replication and an
      antimutator for transition mutations. Its antimutator phenotype is suppressed by
      the L771F mutation (Reha-Krantz, L. J., Stocki, S., Nonay, R., and Maughan, C.
      (1989) J. Cell. Biochem. 13D, 140). We find that the A737V polymerase arrests
      much more frequently than the wild type when polymerizing on primed single
      stranded DNA templates. Although the 3'-->5' exonuclease of the mutant is
      indistinguishable from the wild type on single-stranded DNA, it is more active
      than the wild type on duplex DNA. In a single encounter with the primer, the wild
      type polymerase can incorporate more than 50 nucleotides. The processivity of the
      A737V polymerase is less than the wild type as a polymerase, but is greater than
      the wild type as an exonuclease. The L771F polymerase resembles the wild type in
      each of these properties, while the double mutant (A737V, L771F) is intermediate
      between the two single mutants. Kinetic studies of wild type T4 DNA polymerase
      (Capson, T. L., Peliska, J. A., Kaboord, B. F., Frey, M. W., Lively, C.,
      Dahlberg, M., and Benkovic, S. J. (1992) Biochemistry 31, 10984-10994) suggest
      that DNA binds first to the polumerase active site, before adopting a
      configuration in which it can be hydrolyzed by the exonuclease. Within this
      framework, our studies suggest that DNA moves more readily from the polymerase-
      to the exonuclease-competent configuration on the A737V mutant polymerase, and
      that this movement is decreased by the compensating L771F mutation.

PMID- 8276834
TI  - Interaction of DNA polymerase and DNA helicase within the bacteriophage T4 DNA
      replication complex. Leading strand synthesis by the T4 DNA polymerase mutant
      A737V (tsL141) requires the T4 gene 59 helicase assembly protein.
AB  - The bacteriophage T4 tsL141 (A737V) mutant in T4 DNA polymerase is temperature
      sensitive for DNA replication and an antimutator for some types of mutations. In
      the accompanying paper (Spacciapoli, P., and Nossal, N. G. (1993) J. Biol. Chem.
      269, 438-446), we show that the purified A737V T4 DNA polymerase is less
      processive than the wild type enzyme as a polymerase, but is more processive as
      an exonuclease. The bacteriophage T4 multienzyme replication complex
      reconstituted with the A737V mutant polymerase is defective in both lagging and
      leading strand synthesis. On lagging strand templates, the A737V polymerase is
      stimulated by the gene 44/62 and 45 polymerase accessory proteins and the gene 32
      DNA binding protein, but is still arrested at pause sites much more frequently
      than the wild type. In contrast to wild type T4 DNA polymerase, the A737V
      polymerase does not catalyze leading strand synthesis on a forked duplex template
      with the polymerase accessory proteins, 32 protein, and the gene 41 protein
      helicase. The A737V polymerase requires the T4 gene 59 helicase assembly protein,
      as well as the other proteins, to carry out this reaction. Each of these defects
      is suppressed by the intragenic L771F mutation that suppresses the antimutator
      phenotype of the A737V, polymerase in vivo (Reha-Krantz, L. J., Stocki, S.,
      Nonay, R., and Maughan, C. (1989) J. Cell. Biochem. 13D, 140).

PMID- 8276835
TI  - Complex alternative RNA splicing of epsilon-immunoglobulin transcripts produces
      mRNAs encoding four potential secreted protein isoforms.
AB  - In RNA from human IgE-producing lymphocytes, we previously discovered two
      alternatively spliced epsilon-immunoglobulin mRNA isoforms that encode a novel
      secreted form of IgE and a membrane-bound species. Further analysis using epsilon
      specific reverse transcriptase polymerase chain reactions has elucidated several
      additional alternatively spliced species of epsilon mRNA. One RNA isoform is
      generated by splicing the CH4 exon to a novel distal splice acceptor site,
      forming an epsilon RNA species (designated CH4-M2") that encodes a secreted
      epsilon protein 6 amino acids larger than the classic secreted epsilon protein.
      The other three novel epsilon RNAs are generated by splicing from within CH4 to a
      new exon structure (designated CH5) that is located between CH4 and the membrane
      exons. Since the three new mRNAs using CH5 share the same stop codon in CH5, they
      all encode the same novel protein, which is 10 amino acids shorter than the
      classic secreted epsilon heavy chain. The new alternatively spliced epsilon mRNAs
      reported here, in addition to the previously reported forms encoding membrane and
      larger secreted IgE, appear to reflect the normal splicing pattern in humans, as
      we have detected all these epsilon RNAs in all the human IgE-secreting cells and
      cell lines tested.

PMID- 8276836
TI  - The human alpha 2 integrin gene promoter. Identification of positive and negative
      regulatory elements important for cell-type and developmentally restricted gene
      expression.
AB  - The alpha 2 beta 1 serves as a collagen receptor or a collagen/laminin receptor,
      depending upon cell type. Expression of the integrin is regulated during normal
      cellular differentiation and is altered during carcinogenesis. We have previously
      demonstrated that increased expression of the alpha 2 beta 1 integrin during
      megakaryocytic differentiation is a consequence of increased alpha 2 mRNA due to
      transcriptional activation of the alpha 2 integrin gene and that the decreased
      expression of the integrin in breast adenocarcinoma is due to decreased steady
      state levels of alpha 2 mRNA. We now report the identification and
      characterization of the 5'-flanking region of the alpha 2 integrin gene. The 5'
      untranslated region of the alpha 2 mRNA extends 129 base pairs 5' to the site of
      translation initiation. The promoter region lacks TATA and CAAT boxes but
      contains an abbreviated initiator sequence and six Sp1 binding sites. Consensus
      binding sites for AP-1 and AP-2 complexes, a GATA box, a Pu.1 box, and two
      palindromic motifs with potential to bind the estrogen receptor are also present.
      A 961-base pair fragment of the 5'-flanking region directs both cell type- and
      differentiation-specific expression of a reporter gene in T47-D epithelial cells
      and in pluripotent hematopoietic K562 cells upon megakaryocytic differentiation.

PMID- 8276837
TI  - Temperature-induced inversion of allosteric phenomena.
AB  - Two instances, involving the enzymes carbamoyl-phosphate synthetase from
      Escherichia coli and phosphofructokinase from Bacillus stearothermophilus,
      respectively, are described in which increasing temperature alone causes the
      actions of an allosteric ligand to change from inhibition to activation. In
      neither case are these effects due to a change in the activation energy of the
      enzyme catalyzed reaction induced by the allosteric ligand. Rather, they are due
      to temperature-dependent changes in the extent to which the binding of allosteric
      ligand modifies the affinity of the enzyme for substrate. The data can be readily
      explained by an analysis of the apparent delta H and delta S components of the
      coupling free energy, which quantitatively describe the actions of allosteric
      ligands that act in this manner. These observations underscore the shortcomings
      of expecting to explain the actions of an allosteric ligand solely by the
      structural perturbations that accompany the binding of an allosteric ligand such
      as those often revealed by x-ray crystallography.

PMID- 8276838
TI  - Photoaffinity-labeling peptide substrates for farnesyl-protein transferase and
      the intersubunit location of the active site.
AB  - --CAAX motif peptides, which are substrates for isoprenylation, were
      synthetically derivatized with the light-sensitive benzophenone (Bz) group in
      order to determine their potential use as catalytic site-directed covalent
      photocross-linking ligands for one of the enzymes catalyzing protein
      isoprenylation, farnesyl-protein transferase (FPTase). Bz-peptides could be
      synthesized with [3H]benzophenone and possessed eiter one or two benzophenone
      groups located at or near the peptide's NH2 terminus (e.g. the mono-Bz probes Bz
      ACVIM and Bz-LPCVVM, and the di-Bz derivatized probe Bz-GY-(Bz)PCVVM, referred to
      as Bz2-GYPCVVM). Each type of derivatized peptide behaved as a substrate for
      farnesylation in vitro without irradiation, while under 366-nm irradiation each
      demonstrated covalent cross-linking ability as a catalytic site-directed
      photoaffinity ligand with tissue-purified or enriched but impure fractions from
      rat and bovine brain FPTase, as well as with a recombinant human FPTase variant,
      FPTase (beta alpha t) expressed in Escherichia coli. Without photoactivation, Bz
      ACVIM yielded a Kd of 37 nM for the cloned variant of human FPTase. Pseudo first
      order photolytic inhibition of FPTase preparations with Bz-peptides, as well as
      protection from photoinactivation by unmodified -CAAX motif peptides, supported
      the capacity of these Bz-peptides to serve as co-substrates and their specificity
      for seeking the catalytic site of the enzyme. SDS-polyacrylamide gel
      electrophoresis analysis subsequent to photolysis indicated that the mono-Bz
      derivatized peptides (e.g. [3H]Bz-LPCVVM or 3H]Bz-ACVIM) became covalently cross
      linked preferentially to the approximately 49-kDa beta subunit of the alpha beta
      dimeric FPTase. The farnesyl-PP cosubstrate bound equally well to unmodified and
      Bz-ACVIM-labeled enzyme. The di-Bz derivative, [3H]Bz2-GYPCVVM, in contrast,
      revealed exclusive photocovalent cross-linking with a species of molecular mass
      approximately 95-97 kDa, indicating that both FPTase subunits were tethered
      together covalently by the di-Bz probe. Similar differential SDS-polyacrylamide
      gel electrophoresis cross-linking patterns were obtained with homogeneous FPTases
      as well as with partially purified rat or bovine brain enzyme preparations. The
      absence of nonspecific photolabeling of any proteins in the partially purified
      rat or bovine brain enzyme preparations other than FPTase independently attested
      to the high efficiency of photocross-linking of the FTPase, and the selective
      catalytic site-seeking ability of these Bz-derivatized peptide substrates,
      verifying their potential as structural probes for the active site domain on the
      enzyme.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8276839
TI  - Differential regulation of the two xGATA-1 genes during Xenopus development.
AB  - Xenopus laevis provides an established developmental system to study the
      regulation of cell lineage establishment and the generation of tissue-specific
      patterns of gene expression. We have isolated from Xenopus erythroid cell RNA two
      distinct cDNA clones encoding the xGATA-1 transcription factor. We have
      identified, in erythroid nuclear extracts, the sequence-specific DNA-binding
      protein they encode. By characterizing the expression patterns for RNA derived
      from two distinct homologues, we find that the two xGATA-1 genes are
      differentially regulated. The xGATA-1a mRNA predominates in embryos prior to
      terminal differentiation of erythroid cells, while the differentiated cells
      contain RNA derived predominantly from the xGATA-1b gene. Both proteins activate
      a target globin promoter in transient transfection assays. During early
      development, GATA-1 transcripts are localized to ventral regions of the embryo.
      GATA-1 should therefore provide a useful early marker for studying signalling
      pathways which result in the generation of ventral mesoderm. The differentially
      regulated genes may be distinct markers for targets of ventral mesoderm
      induction.

PMID- 8276840
TI  - Sequence-specific interactions of UvrABC endonuclease with psoralen interstrand
      cross-links.
AB  - The nature of the Uvr protein-DNA complexes formed on psoralen-DNA interstrand
      cross-links was analyzed by DNase I footprinting and correlated with the incision
      efficiency of the UvrABC endonuclease on the cross-links of different DNA
      sequences. Our results indicate that the repair specificity is dependent on the
      DNA sequence and the psoralen orientation in the cross-link. On the strand that
      will be cut, a 30-nucleotide long UvrAB footprint with a DNase I hypersensitive
      site at the 11th nucleotide 5' to the lesion was observed and subsequently
      rearranged to a 22-nucleotide long UvrB-lesion footprint. On the strand that will
      not be cut, the UvrAB-lesion footprint had no 5' DNase I hypersensitive site and
      did not form the UvrB-lesion footprint. Although UvrABC incision requires the
      formation of UvrB-lesion complex on the strand which will be cut, the affinities
      of these complexes do not correlate with the incision efficiencies, suggesting
      that the overall reaction can be driven forward by a favorable next step such as
      UvrC incision. A study of the time-dependent interconversion of UvrAB-lesion
      complex to UvrB-lesion complex on a cross-link revealed a secondary recognition
      of the UvrB-lesion complex by UvrA2(B) proteins in vitro.

PMID- 8276841
TI  - Identification of a DNA-binding protein (keratinocyte transcriptional protein-1)
      recognizing a keratinocyte-specific regulatory element in the 230-kDa bullous
      pemphigoid antigen gene.
AB  - We have recently cloned and characterized the entire human 230-kDa bullous
      pemphigoid antigen gene, which is expressed at a relatively high level in the
      basal keratinocytes. A putative AP2 binding sequence (KRE2), identified in the
      position -1786 to -1778, was cloned in front of a heterologous thymidine kinase
      chloramphenicol acetyltransferase construct, and transient transfections of
      normal human keratinocytes indicated a marked enhancement of the promoter
      activity. Normal human keratinocyte nuclear extracts contained a protein,
      designated as keratinocyte transcriptional protein-1 (KTP-1), which complexed
      with the KRE2 oligomer when examined by gel mobility shift assays. This protein
      was not detected in human skin fibroblast or HeLa cell nuclear extracts that did,
      however, contain AP2. UV cross-linking studies and Southwestern analyses
      suggested that KTP-1 binds to DNA as a single polypeptide of approximately 110
      kDa. These data suggest that KTP-1 is a DNA-binding protein clearly distinct from
      AP2, and this protein may be responsible for the basal keratinocyte-specific
      expression of the bullous pemphigoid antigen gene.

PMID- 8276842
TI  - The association of endogenous Go alpha with the purified omega-conotoxin GVIA
      receptor.
AB  - Modulation of the neuronal omega-conotoxin GVIA-sensitive N-type voltage
      dependent calcium channel (VDCC) by neurotransmitters and guanine nucleotides
      suggests a dynamic interaction between activated G-protein alpha subunits and the
      N-type VDCC. Our previous report on the purification of the N-type VDCC (McEnery,
      M. W., Snowman, A. M., Sharp, A. H., Adams, M. E., and Snyder, S. H. (1991) Proc.
      Natl. Acad. Sci. U.S.A. 88, 11095-11099), has led us to investigate a possible
      association of CTXR with an endogenous G alpha subunit. The addition of the G
      protein activator AIF4- modulated the 125I-CTX binding characteristics of the
      solubilized CTXR. Further immunological analyses employing G alpha subunit
      specific antibodies to monitor the cofractionation of G alpha with 125I-CTX
      binding activity throughout the purification procedure indicate the selective
      recovery of Go alpha in the purified CTXR preparation, as neither Gs alpha, Gi
      alpha, nor G beta gamma could be detected. Furthermore, Go alpha associated with
      CTXR acted as a substrate for pertussis toxin-dependent ADP-ribosylation only
      upon the addition of exogenous G beta gamma subunits. These results strongly
      indicate a high affinity complex between an activated Go alpha and CTXR
      maintained throughout biochemical purification of the 125I-CTX receptor.

PMID- 8276843
TI  - Absence of intramolecular disulfides in the structure and function of native rat
      glucocorticoid receptors.
AB  - The presence of intramolecular disulfides in different functional states of the
      native glucocorticoid receptor in the absence of added oxidants has been examined
      on nonreducing SDS-polyacrylamide gels. Possible disulfides were trapped by the
      reaction of thiols in crude receptor solutions with methyl methanethiolsulfonate
      or iodoacetamide. The presence of diffuse bands at lower molecular weights than
      either the fully reduced or the thiol-blocked species for both the intact 98-kDa
      receptor and the 42-kDa chymotryptic fragment was diagnostic of an intramolecular
      disulfide(s) that had undergone thiol-disulfide rearrangements. However, both the
      rearrangements and the formation of intramolecular disulfides were found to occur
      only with denatured receptors during gel analysis. It appears that the thiols
      normally complexed with zinc in the zinc fingers may be recruited for disulfide
      bond formation. Finally, even when a documented intramolecular disulfide was
      formed in solutions of the native protein, thiol-disulfide rearrangements did not
      occur. The tertiary structure of the receptor is thus constituted in a manner
      that not only limits the formation of disulfides but also prevents the usually
      facile rearrangements of disulfide bond-containing structures to receptor forms
      that may have greatly reduced activity. Therefore, although intramolecular
      disulfide bonds may be of transitory importance, the structural or functional
      changes of native glucocorticoid receptors that are associated with steroid
      binding, activation, and dissociation of heat shock protein 90 neither involve
      nor require the formation or reduction of stable intramolecular disulfides.

PMID- 8276844
TI  - Apoprotein B structure and receptor recognition of triglyceride-rich low density
      lipoprotein (LDL) is modified in small LDL but not in triglyceride-rich LDL of
      normal size.
AB  - We compared the effect of lipid composition and particle size of triglyceride
      rich low density lipoprotein (LDL) upon apoprotein B conformation and binding to
      the LDL receptor. Three groups of triglyceride-rich LDL were studied: (a) LDL
      isolated from chronic hypertriglyceridemic individuals (HTG-LDL); (b) normal LDL
      made triglyceride-rich by in vitro incubation with triglyceride emulsion and the
      neutral lipid transfer protein (R-LDL); and (c) LDL from normolipidemic
      individuals made acutely hypertriglyceridemic by intravenous infusion of 10%
      Intralipid (IV-LDL). HTG-LDL was small and dense, whereas R-LDL and IV-LDL had
      normal size. HTG-LDL, but not R-LDL or IV-LDL, exhibited decreased binding to the
      LDL receptor on human skin fibroblasts in studies at 4 degrees C and reduced
      degradation at 37 degrees C. Apoprotein B conformation was assessed by circular
      dichroism and by analyzing the immunoreactivity of different monoclonal
      antibodies. HTG-LDL but not R-LDL or IV-LDL showed a change in the CD spectra and
      a consistent decrease in the immunoreactivity of monoclonal antibody 3F5 (2.5
      fold) which recognizes an epitope adjacent to the receptor binding domain of
      apoprotein B. These findings suggest that in triglyceride-rich LDL, the relative
      content of neutral lipid in the core of LDL in the absence of changes in the size
      of the particle does not significantly affect apoprotein B conformation or its
      affinity for the LDL receptor.

PMID- 8276845
TI  - A new proline-rich protein precursor expressed in the salivary glands of the rat
      is encoded by a gene homologous to the gene coding for the prohormone-like
      protein SMR1.
AB  - A gene encoding a prohormone-like protein (SMR1) has previously been
      characterized and shown to be expressed in the rat submandibular glands under
      androgenic control (Rosinski-Chupin, I., Tronik, D., and Rougeon, F. (1988) Proc.
      Natl. Acad. Sci. U.S.A. 85, 8553-8557). This gene, now named VCS-alpha 1, belongs
      to a multigene family (Rosinski-Chupin, I., and Rougeon, F. (1990) DNA Cell Biol.
      9, 553-559). We now describe the structure and the expression of a second member
      (VCS-beta 1) of this family. The two genes differ principally in the protein
      coding region, therefore we have named these related genes VCS (variable coding
      sequence). Genomic clones containing the VCS-beta 1 gene were obtained by
      screening a lambda EMBL3 library with a probe corresponding to the VCS-alpha 1
      cDNA. The nucleotide sequence of VCS-beta 1 predicted a structure containing
      three exons. This structure, confirmed by sequencing a VCS-beta 1 cDNA obtained
      by reverse polymerase chain reaction, is identical to the organization of the VCS
      alpha 1 gene. Comparison of the VCS-beta 1 and VCS-alpha 1 genomic sequences
      indicates regions of homology which are unevenly distributed, suggesting a
      differential evolution of some areas (particularly the third exon) of the VCS
      genes. The VCS-beta 1 cDNA codes for a proline-rich protein precursor named PR-V
      beta 1 (148 amino acids, 39.2% proline, 10.8% glycine) and characterized by a
      secretory signal-peptide and three repeats of a unit rich in proline residues
      surrounded by two clusters of potential endoprotease cleavage sites. mrNA coding
      for PR-V beta 1 was detected in the submandibular-sublingual gland complex of
      male and female rats. PR-V beta 1 is homologous to the proline-rich peptide B
      isolated from human saliva (Isemura, S., Saitoh, E., and Sanada, K. (1979) J.
      Biochem. (Tokyo) 86, 79-86) and to the submandibular proline-rich protein
      precursor MSG1 of the mouse (D. Tronik-Le Roux, M. Senorale-Pose, and F. Rougeon,
      manuscript in preparation). Our observations provide evidence that in addition to
      the known proline-rich protein genes, there is, in rodent and probably human
      genomes, another class of genes coding for salivary proline-rich proteins. The
      high conservation of various sites for bacterial collagenases localized in the
      repeat region of PR-V beta 1, MSG1, and PRP-B suggest a protective function of
      these proteins in the oral cavity.

PMID- 8276846
TI  - Molecular cloning and the COOH-terminal processing of gp64, a putative cell-cell
      adhesion protein of the cellular slime mold Polysphondylium pallidum.
AB  - The cellular slime mold Polysphondylium pallidum expresses a cell surface
      glycoprotein (referred to as gp64), which seems to be implicated in cell-cell
      adhesion. We identified a near full-length gp64 cDNA (1,104 base) upon screening
      a P. pallidum lambda gt11 library with a monoclonal antibody. The open reading
      frame encodes a protein of 320 amino acids with a molecular mass of 32,752 Da;
      the protein includes hydrophobic segments at both a NH2- and a COOH-terminal
      ends. By an Edman degradation analysis of S-pyridylethylated gp64 and its COOH
      terminal peptide, it was found that the NH2- and COOH-terminal segments are both
      removed from the precursor protein of gp64. The COOH-terminal segment was
      isolated from a lysyl endopeptidase digest of gp64 by an affinity method. The
      COOH-terminal segment was identified at positions 266-279 in the primary sequence
      deduced from the cDNA sequence. The mature gp64 consisted of 279 amino acid
      residues and extremely rich in Cys residues (36 Cys/279 amino acids = 12.9%).
      Although there was already maximal accumulation of gp64 mRNA in vegetative cells,
      the protein reached a maximal level during aggregation stage, decreased, and then
      leveled off through the developmental cycle.

PMID- 8276847
TI  - Secretion from rat basophilic RBL-2H3 cells is associated with diphosphorylation
      of myosin light chains by myosin light chain kinase as well as phosphorylation by
      protein kinase C.
AB  - The phosphorylation of myosin light chains and heavy chains by protein kinase C
      is known to be temporally correlated with Ca(2+)-dependent secretion of granules
      from RBL-2H3 cells (Ludowyke, R. I., Peleg, I., Beaven, M. A., and Adelstein, R.
      S. (1989) J. Biol. Chem. 264, 12492-12501). We now report that whereas myosin
      light chains are predominantly monophosphorylated by the Ca2+/calmodulin
      dependent myosin light chain kinase at serine 19 in unstimulated cells,
      stimulation of RBL-2H3 cells with antigen or other stimulants causes additional
      phosphorylation of myosin light chains by myosin light chain kinase at threonine
      18, as well as by protein kinase C at serine 1 or serine 2. This
      diphosphorylation at serine 19 and threonine 18 by myosin light chain kinase and
      the monophosphorylation by protein kinase C is correlated with the rate and
      extent of degranulation. Secretion occurs whenever phosphorylation by both
      enzymes is stimulated by antigen or by the combination of low concentrations of
      A23187 (50 nM) and phorbol 12-myristate 13-acetate (20 nM). These
      phosphorylations appear to be closely associated with exocytosis in RBL-2H3
      cells. Thus, phosphorylation, as well as secretion, can be blocked by the kinase
      inhibitors KT5926 and ML-7. More specifically, phorbol ester alone induces
      phosphorylation of myosin light chains by protein kinase C exclusively, but fails
      to induce secretion until accompanied by low concentrations of A23187, which
      activates myosin light chain kinase. Conversely, selective suppression of
      phosphorylation by protein kinase C (with Ro31-7549 in antigen-stimulated cells)
      suppresses degranulation, thereby indicating a requirement for protein kinase C.

PMID- 8276848
TI  - A Limulus intracellular coagulation inhibitor with characteristics of the serpin
      superfamily. Purification, characterization, and cDNA cloning.
AB  - A Limulus intracellular coagulation inhibitor, designated LICI, was isolated from
      hemocytes of the Japanese horseshoe crab (Tachypleus tridentatus), using three
      steps of chromatography, including dextran sulfate-Sepharose CL-6B, Sephacryl S
      200, and Mono S. LICI is a single-chain glycoprotein with an apparent M(r) =
      48,000 estimated by SDS-polyacrylamide gel electrophoresis. It blocks the
      amidolytic activities of Limulus lipopolysaccharide-sensitive serine protease,
      factor C, by forming a covalent 1:1 complex with the protease. The second-order
      rate constant for inhibition of factor C was 2.5 x 10(6) M-1 s-1 at 37 degrees C.
      LICI also inhibited human alpha-thrombin, rat salivary kallikrein, bovine
      plasmin, and trypsin but not Limulus clotting enzyme, Limulus factor B, bovine
      factor Xa, human factor XIa, human tissue plasminogen activator, human urokinase,
      chymotrypsin, elastase, and papain. Glycosaminoglycans such as heparin and
      heparan sulfate had no effect on the inhibitory activity. A cDNA coding for LICI
      was isolated from a hemocyte cDNA library. The open reading frame of the 1,257
      base pair cDNA codes for the mature protein of 394 amino acids, of which 223
      residues were confirmed by amino acid sequence analysis. LICI shows significant
      sequence identities to members of the serpin superfamily, such as human
      plasminogen activator inhibitor type 2 (40%) and human monocyte/neutrophil
      elastase inhibitor (39%). LICI contains a putative reactive site, -Arg-Ser-, at
      the corresponding position present in several inhibitors of the serpin
      superfamily. The subcellular localization, determined using an anti-LICI
      polyclonal antibody, indicated that LICI colocates with the Limulus serine
      protease zymogens in large granules in the hemocyte.

PMID- 8276849
TI  - Role of adenosine 3':5'-monophosphate-dependent protein kinase and cAMP levels in
      ATP-dependent mitogenesis in Swiss 3T3 cells.
AB  - To investigate the role of cAMP-dependent protein kinase (PKA) and cAMP levels in
      ATP-dependent mitogenesis, Swiss 3T3 cells were transfected with an expression
      vector coding for (i) a mutated regulatory subunit of PKA (PKA mutant) or (ii) a
      yeast low Km cAMP phosphodiesterase gene (PDE mutant). The PKA mutant showed 70%
      reduced PKA activity. Phosphodiesterase activity increased 2.5-fold in the PDE
      mutant, leading to a great reduction of cAMP levels stimulated by ATP and other
      cAMP-increasing agents. The mitogenic responses of PKA and PDE mutants to
      insulin, epidermal growth factor, or 12-O-tetradecanoylphorbol-13-acetate were
      not significantly changed. However, the further stimulation by ATP, ADP, and
      adenosine 5'-(beta,gamma-imido)triphosphate in the presence of these growth
      factors was reduced by > 80%. Mitogenic effect of prostaglandin E2, forskolin,
      cholera toxin, or adenosine was inhibited in both mutants. The mitogenic
      stimulation by dibutyryl cAMP, which is resistant to phosphodiesterase, was
      inhibited in the PKA mutant, but not in the PDE mutant. A partial reduction of
      platelet-derived growth factor- or bombesin-stimulated mitogenesis, which
      involves protein kinase C as well as the cAMP signal, was observed in the
      mutants. These genetic results confirm pharmacological data on the role of PKA
      and cAMP levels in mitogenesis due to ATP and other growth factors.

PMID- 8276850
TI  - Mutually exclusive exon use and reactive center diversity in insect serpins.
AB  - We have isolated 38 cDNA clones for serpins from a lepidopteran insect, Manduca
      sexta, and have found that they are identical in sequence, except for a region
      encoding the carboxyl-terminal 40-45 residues, which includes the reactive
      center. Among these clones, there are 11 variants of the reactive center region,
      each encoded by a different version of the ninth exon in the serpin gene. Thus,
      evolution of this insect serpin gene has resulted from duplication and sequence
      divergence of only the exon encoding the reactive site. Alternative pre-mRNA
      splicing then generates inhibitor diversity and the potential to regulate a
      variety of proteinases, using the same protein framework joined to different
      reactive site region cassettes.

PMID- 8276851
TI  - PAY4, a gene required for peroxisome assembly in the yeast Yarrowia lipolytica,
      encodes a novel member of a family of putative ATPases.
AB  - PAY genes are required for peroxisome assembly in the yeast Yarrowia lipolytica.
      Here we characterize one mutant, pay4, and describe the cloning and sequencing of
      the PAY4 gene. The pay4 mutant shows no identifiable peroxisomes by biochemical
      and morphological criteria. The complementing PAY4 gene encodes a polypeptide,
      Pay4p, 1025 amino acids in length and having a predicted molecular mass of
      112,258 Da. The predicted Pay4p sequence contains two putative ATP-binding
      domains and shows structural relationships to other potential ATP-binding
      proteins involved in biological processes as diverse as peroxisome biogenesis,
      vesicle-mediated protein transport, cell cycle control, and transcriptional
      regulation. These proteins all share a highly conserved stretch of approximately
      175 amino acids that contains a consensus sequence for ATP binding. Pay4p shows
      sequence conservation with Pas1p and Pas5p, putative ATPases required for
      peroxisomal assembly in the yeasts Saccharomyces cerevisiae and Pichia pastoris,
      respectively. Pay4p, Pas1p, and Pas5p are presumably related members of a family
      of putative ATPases involved in peroxisome biogenesis. Pay4p is synthesized in
      low amounts in Y. lipolytica cells grown in glucose, and there is a rapid and
      pronounced increase in the levels of Pay4p upon transfer of the cells to a medium
      containing oleic acid as the sole carbon source.

PMID- 8276852
TI  - The pH-dependent membrane association of procathepsin L is mediated by a 9
      residue sequence within the propeptide.
AB  - The lysosomal proprotease procathepsin L binds to mouse fibroblast microsomal
      membranes at pH 5, but mature active cathepsin L does not (McIntyre, G.F., and
      Erickson, A. H. (1991) J. Biol. Chem. 266, 15438-15445). This binding is not
      dependent on N-linked carbohydrate as procathepsin L synthesized in cells treated
      with tunicamycin still shows pH-dependent membrane association. These results
      suggest that the propeptide (Thr18-Lys113) of the cysteine protease mediates its
      pH-dependent membrane association. Synthetic peptides containing either 24 or 9
      residues from the N-terminal portion of the mouse procathepsin L propeptide
      inhibited the binding of mouse procathepsin L to microsomal membranes at pH 5. In
      contrast, the pH-dependent membrane association was not inhibited either by a
      scrambled version of the 24-residue peptide, in which 3 adjacent residues likely
      to be positively charged at pH 5 were dispersed, or by a second control peptide
      containing the 11 N-terminal residues from mature mouse cathepsin L. The 24
      residue peptide chemically coupled to horseradish peroxidase bound to microsomes
      at pH 5, but not at pH 7. On ligand blots, the same conjugate bound specifically
      to a 43-kDa integral membrane protein, identifying the microsomal protein that
      mediates the proenzyme binding. The 9-residue propeptide sequence that inhibits
      the membrane association of procathepsin L at pH 5 resembles the vacuolar sorting
      sequences in the propeptides of yeast proteinase A and carboxypeptidase Y. This
      suggests that the membrane association of procathepsin L may play a role in the
      transport of the proenzyme to lysosomes, the vacuolar equivalent in mammalian
      cells.

PMID- 8276853
TI  - Mutations of vaccinia virus DNA topoisomerase I that stabilize the cleavage
      complex.
AB  - Two mutations in vaccinia virus topoisomerase I, K167D and G226N, have been
      characterized. SOS induction was observed in Escherichia coli expressing vaccinia
      topoisomerase I with either one of these mutations. The mutant enzymes were
      purified to homogeneity and compared with the wild type enzyme for relaxation
      activity and the partial activities of substrate binding, site-specific DNA
      cleavage and DNA religation to determine the mechanism of SOS induction. The
      K167D mutant enzyme had reduced binding affinity for the DNA substrate with a
      Kapp that was 10-fold higher than wild type. Nevertheless, in reactions with high
      enzyme concentration, its substrate cleavage activity was 90% that of wild type.
      The G226N mutant enzyme had virtually wild type binding and cleavage activities.
      However, intermolecular religation by these two mutants were observed to be
      significantly reduced. The cleavage complexes formed with the K167D and G226N
      mutants were more stable to high salt than the wild type cleavable complex. We
      propose that these mutants in vivo induce the SOS response in E. coli due to the
      shift of topoisomerase cleavage-religation equilibrium towards cleavage and
      increased stability of the cleavage complex. The mutation thus has a similar
      effect as the topoisomerase-targeting inhibitors that turn topoisomerases into
      DNA damaging agents.

PMID- 8276854
TI  - Structural and functional characterization of the human decorin gene promoter. A
      homopurine-homopyrimidine S1 nuclease-sensitive region is involved in
      transcriptional control.
AB  - Decorin is a leucine-rich, chondroitin/dermatan sulfate proteoglycan which binds
      collagen and growth factors. We have recently completed the genomic organization
      of human decorin and discovered two alternatively spliced leader exons,
      designated exon Ia and Ib, in the 5'-untranslated region. Initial analysis of the
      sequences upstream to these two exons showed that promoter Ia contained only two
      GC boxes while promoter Ib contained a CAAT and two TATA boxes in close proximity
      to the transcription start site. To determine if these 5'-flanking sequences
      exhibited promoter activity, chimeric chloramphenicol acetyltransferase
      expression plasmids containing the promoter region of either exon Ia or Ib were
      transfected into HeLa and MG-63 osteosarcoma cells. The results showed that only
      the region flanking exon Ib was functional. In vitro transcription assay
      generated two transcripts of 92 and 82 base pairs (bp) indicating that both TATA
      boxes could be used. Using stepwise 5' deletion analysis we found that the
      minimum promoter region at -140 bp from the transcription start site, which
      contained only the CAAT and the two TATA boxes, exhibited strong promoter
      activity. When a larger construct containing an additional 800 bp of upstream
      region was tested, a significant increase in transcriptional activity was
      observed. Interestingly, this promoter region contained several putative binding
      sites for ubiquitous factors (AP1, AP5, and NF-kappa B) and for transforming
      growth factor-beta and a 150-bp homopurine/homopyrimidine element with several
      mirror repeats. When contained in a supercoiled plasmid, this sequence exhibited
      sensitivity to endonuclease S1, an enzyme that preferentially digests single
      stranded DNA. Precise S1 mapping, obtained by direct sequencing of nine distinct
      S1-generated clones, revealed that in all cases the borders of the sensitive
      sequence resided within the pur/pyr segment. We propose that this region of the
      promoter could adopt an intramolecular hairpin triplex structure in vivo and may
      play a role in the chromatin organization at the decorin gene locus. In addition,
      this region was able to up-regulate a minimal heterologous promoter in transient
      transfection assays. The results show that the structure of the decorin gene
      promoter is different from that of any other proteoglycan promoter characterized
      so far and indicate that the pur/pyr segment plays a role in the regulation of
      gene transcription.

PMID- 8276855
TI  - Autocatalytic maturation of the prohormone convertase PC2.
AB  - PC2 is a member of the eukaryotic family of subtilisin-like proteases, which is
      thought to participate in the processing of prohormones and proneuropeptides in
      neuroendocrine cells. PC2 is synthesized as a 69-kDa prepropolypeptide. The NH2
      terminal signal sequence is removed during segregation within the endoplasmic
      reticulum, where glycosylation occurs to generate a 75-kDa propolypeptide. A
      combination of site-directed mutagenesis and a cell-free
      translation/translocation system from Xenopus eggs was used to investigate the
      processing of the pro-PC2 precursor. The 75-kDa polypeptide underwent slow
      cleavage after the sequence Arg-Lys-Lys-Arg84 to generate a 68-kDa mature enzyme.
      Cleavage was blocked when the tetrabasic sequence was deleted (PC2M3) or when the
      active site Asp142 was changed to Asn (PC2M4). This latter observation suggested
      that cleavage of the 75-kDa propolypeptide to the mature 68-kDa enzyme was
      autocatalytic. Incubation of the PC2M4 mutant with the wild type PC2 precursor
      resulted in cleavage of both the wild type polypeptide and the catalytically
      inactive PC2M4 mutant. This indicates that cleavage could occur through an
      intermolecular reaction. The results also demonstrate that the novel Xenopus egg
      extract translation/translocation system represents a powerful cell-free method
      for studying proteolytic processing of propolypeptides.

PMID- 8276856
TI  - Calorimetric evidence for allosteric subunit interactions associated with
      inhibitor binding to band 3 transporter.
AB  - A calorimetric endotherm occurring at 68 degrees C (the C-transition) has been
      assigned previously to the integral domain of band 3 and was shown to be shifted
      to 78 degrees C after covalent binding of 4,4'-diisothiocyanostilbene-2,2'
      disulfonate (DIDS). In this study, we correlate the fractional appearance of the
      shifted C-transition with the fraction of DIDS bound to the band 3 monomer
      population. Our results show a distinctly nonlinear correlation plot with the
      appearance of the shifted C-transition lagging behind DIDS labeling of the band 3
      monomer population. The lag suggests that both monomers of a band 3 dimer must be
      labeled by DIDS in order for the shifted C-transition to appear at 78 degrees C,
      implying that the thermal unfolding of the integral domain of band 3 is modulated
      by allosteric interactions between subunits. This is the first in situ structural
      evidence supporting ligand-mediated subunit interactions within a "carrier"-type
      transporter protein oligomer.

PMID- 8276857
TI  - Inhibition by heparin of thrombin-catalyzed activation of the factor VIII-von
      Willebrand factor complex.
AB  - The activation of factor VIII (fVIII) by thrombin is associated with heavy chain
      cleavages at Arg372 and Arg740 and light chain cleavage at Arg1689. In a defined,
      plasma-free assay of fVIII activation and at physiological ionic strength and pH,
      heparin inhibited the rate of activation of either human or porcine fVIII by
      thrombin in either the presence or absence of von Willebrand factor (vWf). The
      inhibitory effect of heparin was associated with inhibition of all three thrombin
      catalyzed bond cleavages. At plasma concentrations of fVIII (approximately 1 nM)
      and vWf (approximately 35 nM), the rate of fVIII activation was inhibited by 50%
      at approximately 0.1 unit/ml heparin, which is below the normal range of heparin
      concentrations in plasma during therapeutic anticoagulation (0.2-0.7 unit/ml). We
      propose that, in addition to catalyzing the inhibition of thrombin and other
      intrinsic pathway coagulation proteases by antithrombin, heparin functions as an
      anticoagulant by direct inhibition of the activation of the fVIII-vWf complex by
      thrombin.

PMID- 8276858
TI  - A retinoic acid-inducible GATA-binding protein binds to the regulatory region of
      J6 serpin gene.
AB  - Transcription of the J6 gene (a member of the serpin family) is induced in murine
      F9 teratocarcinoma cells 24-48 h after retinoic acid (RA) treatment. Previously,
      we have identified a region of the J6 5'-flanking region (-1050 to -738) that is
      involved in regulating transcription of this gene. In this report, we show that a
      RA-induced nuclear protein in the F9 cell extract recognizes the GAGATAG sequence
      which is repeated four times in this regulatory region of the J6 gene. The
      kinetics of RA induction of the GAGATAG-binding protein correlates with that of
      J6 mRNA, suggesting that the GAGATAG-binding protein may be involved in the
      transactivation of the J6 gene in RA-treated F9 cells. Competition experiments
      demonstrate further that the RA- induced GAGATAG-binding protein is related to
      the transcription factors GATA-1 and GATA-2. Furthermore, insertion of the RA
      regulatory region of the J6 gene into a thymidine kinase promoter/chloramphenicol
      acetyltransferase expression vector causes an increase in chloramphenicol
      acetyltransferase expression by 5-8-fold in human HeLa cells when co-transfected
      with human GATA-2 or GATA-3 expression vectors. This suggests that the J6 gene is
      likely to be transactivated by the GATA-2, GATA-3, or related transcription
      factor, which is activated by retinoic acid during F9 cell differentiation.

PMID- 8276859
TI  - Erythropoietin-dependent association of phosphatidylinositol 3-kinase with
      tyrosine-phosphorylated erythropoietin receptor.
AB  - Erythropoietin (Epo) regulates the proliferation and differentiation of erythroid
      precursors. The Epo receptor (EpoR) belongs to the cytokine receptor family and
      lacks a tyrosine kinase domain. However, Epo induces tyrosine phosphorylation of
      cellular substrates including the EpoR. To explore the functional significance of
      receptor tyrosine phosphorylation, we examined the possible interaction of the
      receptor with the 85-kDa regulatory subunit (p85) of phosphatidylinositol (PI) 3
      kinase. After Epo stimulation, p85 was found to associate with the tyrosine
      phosphorylated 72-kDa form of EpoR as well as a 92-kDa phosphotyrosyl protein,
      and PI 3-kinase activity was detectable in anti-EpoR immunoprecipitates. Anti
      EpoR blotting of anti-p85 immunoprecipitates revealed that p85 binds specifically
      to the 72-kDa form of the EpoR and not to unphosphorylated 66- and 64-kDa forms.
      Association of p85 with the EpoR was Epo dose- and time-dependent and correlated
      with tyrosine phosphorylation of the receptor. Consistent with a role for
      tyrosine phosphorylation of the EpoR, PI 3-kinase did not associate with a
      mitogenically active receptor mutant that lacked tyrosine-phosphorylation sites
      in the carboxyl-terminal region. A recombinant fusion protein containing the
      carboxyl-terminal SH-2 domain of p85 was shown to bind to tyrosine-phosphorylated
      EpoR in vitro. Taken together, these results indicate that, following Epo
      stimulation, the EpoR recruits PI 3-kinase to the cell membrane by binding
      between the carboxyl-terminal SH-2 domain of p85 and the tyrosine-phosphorylated
      carboxyl-terminal region of the receptor. The association with PI 3-kinase is,
      however, not required for the growth signal transduction from the EpoR.

PMID- 8276860
TI  - Cellular transformation and guanine nucleotide exchange activity are catalyzed by
      a common domain on the dbl oncogene product.
AB  - The dbl oncogene product contains a 238-amino acid domain, which is shared by an
      expanding family of growth regulatory proteins. These include the Saccharomyces
      cerevisiae cell division cycle protein, CDC24, the breakpoint cluster region
      protein, the ect2 and vav oncogene products, and the brain GDP-releasing factor
      for Ras. Previous studies have provided evidence that oncogenic Dbl or an
      associated protein stimulates GDP dissociation from the human species (Hs)
      homolog of CDC42. We show here that Dbl specifically complexes with the GDP-bound
      forms of CDC42Hs and RhoA, but not Rac1 or TC10, and that this specificity
      correlates with the ability of Dbl to act as a GDP-releasing factor. Small
      deletions throughout the Dbl domain, which inactivate transformation, eliminated
      the ability of Dbl to stimulate GDP dissociation, whereas deletions outside of
      this domain did not impair either function. Finally, the Dbl domain itself, when
      expressed and purified as a recombinant protein, was shown to stimulate GDP
      dissociation from purified, recombinant CDC42Hs. These findings establish that a
      minimal unit on Dbl that is critical to its transforming function directly
      regulates GDP-GTP exchange activity.

PMID- 8276861
TI  - Dissociation and reassociation of the bovine pituitary multicatalytic proteinase
      complex.
AB  - The eukaryotic multicatalytic proteinase complex (proteasome) is a high molecular
      mass enzyme which contains 13-15 nonidentical subunits of similar size (molecular
      masses of 21-31 kDa), but differing widely in net charge (isoelectric points
      ranging from 3 to 10). At least four catalytic components termed chymotrypsin
      like, trypsin-like, peptidylglutamyl peptide-hydrolyzing, and caseinolytic are
      associated with the proteinase. The catalytic nature of the components is
      unknown, since sequences of cloned subunits bear no homology to known proteinases
      and proteolytically active subunits have not been isolated. Analysis of the
      relationship between structure and catalytic function would be greatly
      facilitated if a means for reversibly dissociating and reassociating the
      proteinase were available. We provide the first evidence of reassembly of
      dissociated multicatalytic proteinase complex into a functional molecule.
      Incubation with the organic mercurial, p-chloromercuribenzoic acid disrupts in a
      concentration-dependent manner the quaternary structure of the enzyme, leading to
      formation of a heterogeneous population of subunits. Dissociation of the complex
      coincides with progressive loss of chymotrypsin-like, trypsin-like, and
      peptidylglutamyl peptide hydrolyzing activities. The caseinolytic activity of the
      residual undissociated enzyme is markedly activated. Exposure of the dissociated
      enzyme to dithiothreitol restores the catalytic profile and reassociates the
      enzyme. Evidence for catalytically active subcomplexes was not obtained
      indicating that structural integrity may be necessary for expression of all
      defined activities.

PMID- 8276862
TI  - Secretion of beta-amyloid precursor protein involves multiple cleavage sites.
AB  - A major histopathological feature of Alzheimer's disease is deposits of a
      approximately 4-kDa beta-amyloid peptide derived by proteolytic processing from a
      precursor, the beta-amyloid precursor protein (beta-APP). Proteolytic cleavage of
      beta-APP within the approximately 4-kDa beta-amyloid domain permits the secretion
      of the amino-terminal portion of beta-APP while concomitantly producing a
      membrane bound approximately 9-kDa carboxyl-terminal fragment. We have
      characterized the proteolytic cleavage site for beta-APP secretion by amino acid
      sequence analysis of the approximately 9-kDa beta-APP carboxyl-terminal cleavage
      product produced by recombinant and native expression systems. Recombinant beta
      APP was generated by a vaccinia virus expression system in CV-1 monkey
      fibroblasts; endogenous beta-APP was obtained using a fibroblast line derived
      from an individual with Down's syndrome. The sequences of both unlabeled and
      metabolically radiolabeled approximately 9-kDa fragment from CV-1 cells reveal
      that the major (60%) secretory cleavage site is after Lys16 of the beta-amyloid
      domain as reported previously; however, an additional cleavage site is seen after
      Phe19 (40%). Radiosequence analysis of the carboxyl-terminal fragment purified
      from Down's syndrome fibroblasts indicates cleavage sites after Phe19, Glu22, and
      Gly25 and not after Lys16. CV-1 cells expressing beta-APP mutants lacking 4 and 6
      amino acids adjacent to Lys16 yielded approximately 9-kDa fragments with two
      identical cleavage sites, neither of which occurred after the retained Lys16 but
      were after Glu11 and His13. These data suggest that secretion of beta-APP
      involves multiple proteinases and that the composition of these proteinases may
      vary within different cell backgrounds.

PMID- 8276863
TI  - Mevalonic acid-dependent degradation of 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase in vivo and in vitro.
AB  - The microsomal enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
      is subject to rapid degradation when cells are incubated with sterols or
      mevalonic acid (MVA). It has been shown that this rapid degradation is dependent
      upon both a sterol and another MVA-derived metabolite (Nakanishi, M., Goldstein,
      J. L., and Brown, M. S. (1988) J. Biol. Chem. 258, 8929-8937). In the current
      study, inhibitors of the isoprene biosynthetic pathway were used to define
      further this mevalonic acid derivative involved in the accelerated degradation of
      HMG-CoA reductase. The accelerated degradation of HMG-CoA reductase in met-18b-2
      cells, which is induced by the addition of MVA, was inhibited by the presence of
      the squalene synthase inhibitor, zaragozic acid/squalestatin, or the squalene
      epoxidase inhibitor, NB-598. Accelerated degradation of HMG-CoA reductase was
      observed when NB-598-treated cells were incubated with both MVA and sterols. In
      contrast, the addition of MVA and sterols to zaragozic acid/squalestatin-treated
      cells did not result in rapid enzyme degradation. This MVA- and sterol-dependent
      degradation of HMG-CoA reductase persisted in cells permeabilized with reduced
      streptolysin O. Finally, the selective degradation of HMG-CoA reductase was also
      observed in rat hepatic microsomes incubated in vitro in the absence of ATP and
      cytosol. We conclude that the MVA-derived component that is required for the
      accelerated degradation of HMG-CoA reductase is derived from farnesyl
      disphosphate and/or squalene in the isoprenoid biosynthetic pathway. We propose
      that this component has a permissive effect and does not, by itself, induce the
      degradation of HMG-CoA reductase. We also conclude that the degradation of HMG
      CoA occurs in the endoplasmic reticulum, and, once the degradation of HMG-CoA
      reductase has been initiated by MVA and sterols, all necessary components for the
      continued degradation of HMG-CoA reductase reside in the endoplasmic reticulum.

PMID- 8276864
TI  - Arachidonic acid down-regulates the insulin-dependent glucose transporter gene
      (GLUT4) in 3T3-L1 adipocytes by inhibiting transcription and enhancing mRNA
      turnover.
AB  - Chronic exposure of fully differentiated 3T3-L1 adipocytes to 50 microM
      arachidonic acid (AA) resulted in an inhibition (approximately 91%) in cellular
      GLUT4 mRNA content after a 48-h exposure, without similarly affecting the mRNA
      content of the ubiquitous glucose transporter, GLUT1. Subsequent investigations
      revealed that transcription of the GLUT4 gene was reduced by approximately 50% in
      response to AA treatment and the half-life of GLUT4 mRNA decreased from 8.0 to
      4.6 h. By contrast, AA increased the accumulation of GLUT1 mRNA by 65%, by a
      mechanism that also involved regulation at both transcriptional and mRNA
      stability levels. Western blot analysis revealed that AA was specifically
      reducing the insulin-responsive glucose transporter (GLUT4) in both plasma and
      intracellular membranes. Subsequently, AA was observed to alter the ability of
      the GLUT4 transporter to respond to insulin and mediate a significant enhancement
      of glucose uptake. The results presented in this study indicate that AA can
      partially mimic the effects of both tumor necrosis factor-alpha and insulin
      which, when chronically supplied to 3T3-L1 adipocytes, also down-regulate GLUT4
      gene expression. Therefore, these data may have relevance to the insulin
      resistance associated with non-insulin-dependent diabetes mellitus.

PMID- 8276865
TI  - Protein tyrosine phosphorylation induced by lysophosphatidic acid in Rat-1
      fibroblasts. Evidence that phosphorylation of map kinase is mediated by the Gi
      p21ras pathway.
AB  - Lysophosphatidic acid (LPA) is a platelet-derived phospholipid that serves as a
      mitogen for fibroblasts. LPA activates its own G protein-coupled receptor(s)
      leading to stimulation of phospholipase C and inhibition of adenylate cyclase.
      Furthermore, LPA rapidly activates p21ras through a pertussis toxin-sensitive
      pathway. In this study, we have examined LPA-induced protein tyrosine
      phosphorylation in Rat-1 fibroblasts. LPA action was compared with that of
      endothelin, which is a stronger activator of phospholipase C than LPA but fails
      to activate p21ras and to stimulate DNA synthesis in these cells. LPA and, more
      effectively, endothelin rapidly stimulate tyrosine phosphorylation of proteins of
      110-130, 95, and 65-75 kDa. The effect of LPA is dose- and time-dependent, being
      half-maximal at 3-30 nM and peaking after 2-5 min. Among the 110-130-kDa group of
      phosphotyrosyl proteins is the 125-kDa "focal adhesion kinase" (p125FAK) but not
      the 120-kDa p21ras GTPase-activating protein. Furthermore, LPA, like epidermal
      growth factor, causes tyrosine phosphorylation and activation of the p42/p44
      mitogen-activated protein (MAP) kinases, paralleling p21ras activation. In
      contrast, endothelin fails to phosphorylate MAP kinase. Treatment of the cells
      with pertussis toxin blocks LPA-induced MAP kinase phosphorylation without
      affecting the other tyrosine phosphorylations. The kinase inhibitor staurosporine
      (1 microM) blocks LPA-induced, but not epidermal growth factor-induced,
      activation of p21ras and MAP kinase, consistent with an intermediate protein
      kinase linking the LPA receptor to p21ras activation. The results support a model
      in which LPA-induced phosphorylation of MAP kinase is mediated by p21ras, and
      tyrosine phosphorylation of the other substrates, including p125FAK, is
      associated with phospholipase C activation.

PMID- 8276866
TI  - Role of interchain disulfide bonds on the assembly and secretion of human
      fibrinogen.
AB  - The cysteines involved in joining the 2 half-molecules of fibrinogen and also
      those located on either side of the alpha-helical coiled-coil region, were
      substituted, by site-directed mutagenesis, with serine. Fibrinogen assembly and
      secretion were determined in transiently transfected COS cells. Our studies
      indicate that in order to assemble the 2 half-molecules into a dimer, it is not
      sufficient to only have the disulfide linkages which keep the 2 half-molecules
      intact. The disulfide rings which flank the coil-coiled region also play
      important roles in dimer assembly. Intact interchain disulfide linkages at the
      NH2-terminal end of the coiled-coil region are essential for assembly of the 2
      half-molecules. Disruption of these disulfide rings leads to the formation and
      secretion of half-molecules. Disruption of the interchain disulfide rings at the
      COOH-terminal end of the coiled-coil region allows dimer formation, but the 6
      chain molecule which is assembled is not secreted. Disruption of both disulfide
      rings at either end of the coiled-coil region disallows assembly of half
      molecules and of dimeric fibrinogen.

PMID- 8276867
TI  - Properties of purified recombinant poliovirus protein 3aB as substrate for viral
      proteinases and as co-factor for RNA polymerase 3Dpol.
AB  - The poliovirus-specific polypeptide 3AB (B = VPg) was expressed in Escherichia
      coli and purified to near homogeneity. Corresponding to its known association
      with membranes in poliovirus-infected HeLa cells, 3AB expressed in E. coli was
      also membrane-associated, and it could be solubilized only in detergent
      containing buffers. In soluble form, 3AB was resistant to digestion with the
      virus-specific proteinases 3Cpro and 3CDpro. However, it was cleaved by these
      enzymes to 3A and VPg when bound to the bacterial membranes, an observation
      suggesting that 3AB may deliver the genome-linked protein VPg to the membrane
      associated poliovirus replication complex. The specific activity of 3CDpro in
      processing 3AB was significantly higher than that of 3Cpro. Soluble 3AB was found
      to stimulate nearly 100-fold poly (A)-dependent, primer-dependent poly(U)
      synthesis, catalyzed by purified poliovirus RNA polymerase 3Dpol. We propose that
      3AB has a dual function in poliovirus genome replication: as a precursor for VPg,
      and as a co-factor for 3Dpol.

PMID- 8276868
TI  - Two binding sites for the plant transcription factor ASF-1 can respond to auxin
      treatments in transgenic tobacco.
AB  - The hormone, auxin, plays an important role in the differentiation and growth of
      plant cells. A number of auxin-responsive genes have been characterized but until
      now minimal auxin-responsive cis-elements within these promoter regions have not
      been identified. Here we show that two related DNA sequences of 21 base pairs can
      respond to auxin treatment in transgenic tobacco. In contrast, treatments with
      cytokinin or abscisic acid do not cause any apparent increase in promoter
      activity of these cis-acting elements. These sequences are present in the
      promoter regions of the nopaline synthase gene from the T-DNA of Agrobacterium
      tumefaciens and the 35 S promoter from cauliflower mosaic virus. Both sequences
      have been shown to be binding sites for the tobacco transcription factor ASF-1.
      Pretreatment of leaves with cycloheximide does not inhibit the response to auxin
      treatment, suggesting that hormone sensitivity of these promoter elements does
      not involve de novo synthesis of ASF-1. In addition, promoter elements from some
      auxin-responsive plant genes can bind ASF-1 in vitro. Based on these results, we
      propose that transcriptional activation by ASF-1 may be modulated by auxin
      through modification of pre-existing factors. Our results also suggest a role for
      ASF-1 in mediating some of the effects of auxin in vivo.

PMID- 8276869
TI  - Characterization of BcgI, a new kind of restriction-modification system.
AB  - The BcgI restriction enzyme from Bacillus coagulans is unusual in that it cleaves
      on both sides of its recognition site, CGAN6TGC, releasing a fragment that
      includes the site and several bases on each side. We report the organization and
      nucleotide sequences of the genes for the BcgI restriction-modification system
      and the properties of the proteins that they encode. The system comprises two
      adjacent, similarly oriented genes. The proximal gene, bcgIA, codes for a 637
      amino acid protein (molecular mass = 71.6 kDa) that resembles certain m6A
      specific DNA-methyltransferases, particularly those that constitute the
      modification subunits of type I restriction-modification systems. The distal
      gene, bcgIB, codes for a 341-amino acid protein (molecular mass = 39.2 kDa) that
      resembles none of the sequences in the sequence data bases. The two genes overlap
      by several nucleotides. Alone, neither protein restricts or modifies DNA, but,
      together, they form a complex in the proportion A2B that does both. DNA binding
      assays showed that the DNA-protein complex can be formed only in the presence of
      both subunits, suggesting that the association of inactive subunits generates the
      active BcgI enzyme that can bind DNA and then either cleaves or methylates at
      target site.

PMID- 8276870
TI  - Overexpression of any fibrinogen chain by Hep G2 cells specifically elevates the
      expression of the other two chains.
AB  - Earlier studies showed that overexpression of B beta fibrinogen chains, by
      transfection of Hep G2 cells with B beta cDNA, specifically enhanced the
      synthesis of all three fibrinogen chains (Roy, S. N., Mukhopadhyay, G., and
      Redman, C. M. (1990) J. Biol. Chem. 265, 6389-6393). To determine whether
      overexpression of any of the three component chains of fibrinogen affects the
      synthesis of the other two chains, we developed stable Hep G2 cell lines
      transfected with individual fibrinogen chain cDNAs. As a control, cells were also
      transfected with expression vector, which did not contain fibrinogen cDNA.
      Transfection with any fibrinogen cDNA increased the synthesis of all three
      fibrinogen chains but not of other plasma proteins. Hep G2 cells transfected with
      B beta cDNA produced 3-4-fold more fibrinogen than control cells, and cells
      transfected with A alpha or gamma cDNA made about 2-fold more fibrinogen.
      Northern blot analyses showed that levels of all 3 fibrinogen mRNAs were
      increased and were highest in Hep G2-B beta cells. Nuclear run-on transcription
      assays demonstrated that increased expression of the chains was due to increased
      transcriptional activity. These studies show that transcription of the three
      fibrinogen chains is tightly linked, and increased expression of any chain
      specifically leads to increased synthesis of the other two chains.

PMID- 8276871
TI  - Molecular cloning and genomic organization of chicken syndecan-4.
AB  - We have cloned and determined the genomic organization of the core protein of the
      chicken transmembrane proteoglycan, syndecan-4. Identification of the initial
      cDNA was accomplished using polyclonal antibodies directed against the
      cytoplasmic domain of murine syndecan-1 core protein. The cDNA for chicken
      syndecan-4 encodes a putative core protein of 197 amino acids which consists of a
      19-amino acid signal peptide, a 125-amino acid ectodomain, a 25-amino acid
      transmembrane domain, and a 28-amino acid cytoplasmic domain. The predicted
      molecular mass of the mature core protein is 19,639 daltons. The ectodomain of
      chicken syndecan-4 core protein contains three potential sites for
      glycosaminoglycan attachment, two sites for N-glycosylation, and lacks a dibasic
      protease cleavage site proximal to the membrane-spanning region found in other
      syndecan family members. Comparison of the complete amino acid sequence with
      human syndecan-4 (amphlican (David, G., van der Schueren, B., Marynen, P.,
      Cassiman, J. J., and van den Berghe, H. (1992) J. Cell Biol. 118, 961-969)) and
      rat syndecan-4 (ryudocan (Kojima, T., Shworak, N. W., and Rosenberg, R. D. (1992)
      J. Biol. Chem. 267, 4870-4877)) indicates an overall identity of 58 and 56%,
      respectively, with a 91 and 92% identity in the highly conserved transmembrane
      and cytoplasmic domains. The core protein of chicken syndecan-4 synthesized by
      chicken cells is modified with heparan sulfate side chains yielding a
      proteoglycan with a molecular mass of > 200 kDa in LMH cells (immortalized male
      leghorn LM strain hepatocytes) and primary skin fibroblasts. Syndecan-4 isolated
      from chondrocyte cultures runs as a diffuse band between 100 and 200 kDa.
      Northern analysis of chicken syndecan-4 indicates three messages with distinct
      sizes of 0.9, 1.3, and 2.9 kb and a wide mRNA tissue distribution. The chicken
      syndecan-4 gene is divided into 5 exons encoding distinct regions which contain
      the signal peptide, the glycosaminoglycan attachment sites, a small spacer of
      unknown function, the glycosylation sites and the transmembrane and cytoplasmic
      domains.

PMID- 8276872
TI  - Platelet-derived growth factor modulation of focal adhesion kinase (p125FAK) and
      paxillin tyrosine phosphorylation in Swiss 3T3 cells. Bell-shaped dose response
      and cross-talk with bombesin.
AB  - In the present study, we have identified several proteins in Swiss 3T3 cells that
      are phosphorylated on tyrosine in response to platelet-derived growth factor
      (PDGF) and exhibit an unusual bell-shaped dose-response curve with a maximum at 5
      ng/ml platelet-derived growth factor (PDGF). These proteins include two that are
      associated with focal adhesions, namely the focal adhesion kinase (p125FAK), a
      novel cytosolic tyrosine kinase, and paxillin. At low concentrations of PDGF (1-5
      ng/ml), these proteins are the predominant tyrosine-phosphorylated species. At 30
      ng/ml PDGF, however, there was no stimulation of their phosphorylation over
      control levels. In contrast, tyrosine phosphorylation of previously described
      substrates of the PDGF receptor tyrosine kinase, namely the p21ras GTPase
      activating protein, p120, phosphatidyl inositol 3' kinase, and phospholipase C
      gamma exhibited sigmoidal dose-response curves with PDGF and were all efficiently
      phosphorylated on tyrosine at 30 ng/ml PDGF. Cytochalasin D, which disrupts the
      actin cytoskeleton, completely inhibited the tyrosine phosphorylation of p125FAK
      and paxillin by PDGF. Examination of the actin cytoskeleton after stimulation of
      cells with different concentrations of PDGF revealed that at 5 ng/ml PDGF, actin
      appears in stress fibers and in membrane ruffles, while at 30 ng/ml, PDGF
      disrupts the actin cytoskeleton. Bombesin stimulates actin stress fiber formation
      with no evidence of disruption of stress fibers at high concentrations. When
      cells were stimulated with bombesin (10 nM) in the presence of 30 ng/ml PDGF,
      however, the actin cytoskeleton was completely disrupted. Further, the tyrosine
      phosphorylation of both p125FAK and paxillin induced by bombesin (10 nM) was
      completely prevented when cells were stimulated with bombesin in the presence of
      30 ng/ml PDGF. We propose that the inhibitory limb in the bell-shaped dose
      response curve of PDGF and the novel cross-talk between PDGF and bombesin on
      tyrosine phosphorylation may be explained by the ability of PDGF at 30 ng/ml to
      disrupt the actin cytoskeleton.

PMID- 8276874
TI  - Characterization of intra- and intermolecular DNA ligation mediated by eukaryotic
      topoisomerase I. Role of bipartite DNA interaction in the ligation process.
AB  - The capacity of eukaryotic topoisomerase I to catalyze intra- and intermolecular
      DNA strand transfer via a two-step cleavage/ligation reaction was investigated by
      use of purified enzyme and defined DNA substrates. Topoisomerase I-mediated
      cleavage requires separate interaction with a duplex region encompassing the
      cleavage site (region A) and a duplex region located on the side holding the 5'
      OH end generated by cleavage (region B). Cleaved topoisomerase I-DNA complexes
      containing enzyme covalently attached at internal and terminal positions were
      employed to characterize the intra- and intermolecular ligation reactions. Enzyme
      attached covalently at an internal position of a partially single-stranded DNA
      molecule is able to catalyze ligation of a complementary dinucleotide within
      region A in the absence of interaction with region B. Moreover, the dinucleotide
      confines the minimal DNA acceptor for intramolecular ligation. Topoisomerase I
      attached covalently to DNA at a terminal position can ligate the cleaved strand
      to heterologous duplex DNA regardless of sequence, whereas ligation does not
      proceed with single-stranded DNA. When these features are considered together
      with the observation that intermolecular ligation is inhibited by 1 M NaCl, it
      suggests that the reaction requires bipartite DNA interaction. A model is
      proposed that relates the bipartite DNA binding of eukaryotic topoisomerase I to
      the catalytic functions.

PMID- 8276873
TI  - Identification of N-acetylcysteine as a new substrate for rat liver microsomal
      glutathione transferase. A study of thiol ligands.
AB  - N-Acetyl-L-cysteine serves as an efficient substrate for the rat liver microsomal
      glutathione transferase with 1-chloro-2,4-dinitrobenzene as second substrate (8.8
      +/- 0.37 mumol/min mg). The activity is actually higher than that obtained with
      glutathione (2-4 mumol/min mg). In examining the activity of liver subcellular
      fractions, no activity with N-acetyl-L-Cys could be detected in dialyzed or N
      ethylmaleimide-treated (in order to remove endogenous glutathione) cytosol. The
      activity in rat liver microsomes was 0.11 +/- 0.007 mumol/min mg, which is
      accounted for by the content of microsomal glutathione transferase. Thus, N
      acetyl-L-Cys can be used as a specific substrate for determining the conjugating
      activity of microsomal glutathione transferase. N-Acetyl-L-Cys was also shown to
      function as a substrate for the enzyme when other second substrates than 1-chloro
      2,4-dinitrobenzene (with varying electrophilicity) are used. The pH dependence of
      microsomal glutathione transferase was studied. The kcat/Km(1-chloro-2,4
      dinitrobenzene) was dependent on pH with an apparent pKa of 6, > or = 9, and > or
      = 8 with saturating glutathione, gamma-L-Glu-L-Cys, and N-acetyl-L- cysteine,
      respectively. Apparently the enzyme has the ability to lower the pKa of
      glutathione by 3 orders of magnitude. The kcat/Km(thiol) did not vary appreciably
      with pH (except for N-acetyl-L-cysteine), indicating that no rate-determining
      deprotonation occurs on the enzyme itself between pH 5.5 and 9. The abilities of
      histidine-, lysine-, and arginine-selective reagents to inactivate the enzyme
      when N-acetyl-L-cysteine and gamma-L-Glu-L-Cys were used as substrates were
      investigated. The activity toward N-acetyl-L-cysteine was decreased considerably
      less after treatment with the arginine-selective reagent phenylglyoxal, as
      compared to the activity toward GSH and gamma-L-Glu-L-Cys. This indicates that an
      arginine makes contact with gamma-L-Glu residue in GSH. With the other
      reagent/substrate combinations tested the enzyme was inactivated almost
      completely. The ability of microsomal glutathione transferase to stabilize the
      Meisenheimer complex formation between 1,3,5-trinitrobenzene and various
      glutathione analogues, including non-substrate thiols, has been examined. It is
      shown that, in general, substrates exhibited higher formation constants
      (approaching 50 mM-1) than non-substrates (4.5 +/- 1.7 mM-1, n = 7), whereas
      simpler thiols did not yield enzyme-bound complexes. The fact that the enzyme can
      stabilize Meisenheimer complexes from non-substrate thiol analogues of
      glutathione offers new possibilities for examining the substrate interactions of
      glutathione transferases.

PMID- 8276875
TI  - Repair of O6-methylguanine and O4-methylthymine by the human and rat O6
      methylguanine-DNA methyltransferases.
AB  - In order to compare the ability of the human and rat O6-methylguanine-DNA
      methyltransferases (transferases) to repair in vitro O6-methylguanine (O6-MeGua)
      and O4-methylthymine (O4-MeThy) residues, which are two mutagenic DNA adducts
      formed by alkylating agents, we have purified both proteins to homogeneity. Gel
      electrophoresis of the proteins shows that the O4-MeThy repair is due to the
      transfer of the methyl group from the alkylated base to the transferase
      molecules. However, both proteins repair with different efficiencies the O6-MeGua
      and O4-MeThy residues present in alkylated DNA, poly[d(G.C)], poly(dG.dC), or in
      alkylated poly[d(A.T)] and poly(dA.dT), respectively. Reaction of both proteins
      with either methylated residues follows a second-order kinetics. The rate
      constants are 1 x 10(9) M-1 min-1 for both proteins acting on O6-MeGua and 4.8 x
      10(6) or 1.8 x 10(5) M-1 min-1 for the rat or human protein acting on O4-MeThy,
      respectively. The activity of the mammalian transferases on O4-MeThy present in a
      poly(dA.dT) substrate is inhibited by double-stranded DNA.

PMID- 8276876
TI  - Antigen recognition by an antibody light chain.
AB  - A monoclonal antibody to vasoactive intestinal polypeptide (VIP) was reduced and
      alkylated and its light and heavy chains were purified by denaturing gel
      filtration. Following renaturation, the light chain displayed sequence-specific
      binding of VIP. The specific VIP binding activity of several fractions spanning
      the light chain peak recovered from the gel filtration column was constant, the
      light chain was electrophoretically homogeneous, the VIP binding activity was
      precipitated by anti-light chain antibody but not anti-heavy chain antibody and
      the activity remained associated with a light chain fraction recovered by
      resolutive chromatography on a hydroxylapatite column. N-terminal amino acid
      sequencing of the light and heavy chain fractions confirmed the purity of these
      proteins and suggested that the VL and VH regions belonged to kappa-family II and
      gamma-family III, respectively. The VIP-binding affinity of the light chain was
      only 5-fold lower than that of the parent antibody and the light chain did not
      bind unrelated peptides. These observations suggest that light chains display
      structural characteristics necessary for high affinity antigen binding.

PMID- 8276877
TI  - Saccharomyces cerevisiae U14 small nuclear RNA has little secondary structure and
      appears to be produced by post-transcriptional processing.
AB  - Yeast U14 small nuclear (sn) RNA is required for normal processing of rRNA. The
      sequence and folding properties of U14 were analyzed in the present study, with
      the aim of defining the structures of natural U14 subspecies and characterizing
      the folding properties of free U14 RNA. Natural U14 was determined to consist of
      four subspecies of 125-128 nucleotides, none containing a 5'-cap structure.
      Length heterogeneity occurs at both ends and is presumed to reflect post
      transcriptional processing of U14 precursors. Results from nuclease and chemical
      probing revealed that U14 has surprisingly little secondary structure overall.
      Three essential sequence elements conserved among all U14 RNAs occur in regions
      that are largely single-stranded, i.e. box C, box D, and a 13-nucleotide segment
      complementary to 18 S rRNA; a non-essential 14-nucleotide sequence complementary
      to 18 S rRNA is also unpaired. Two non-conserved segments required for activity
      are part of a stably folded 32-base domain that is unique to yeast U14. Finally,
      a 5'-, 3'-stem shown earlier to be required for U14 accumulation appears to exist
      only in precursors to U14 and not in protein-free mature RNA. The implications of
      these results are discussed in terms of U14 synthesis and function.

PMID- 8276878
TI  - The REC1 gene of Ustilago maydis involved in the cellular response to DNA damage
      encodes an exonuclease.
AB  - Mutation in the REC1 gene of Ustilago maydis is known to lead to a complex
      phenotype with alterations in DNA repair, recombination, mutagenesis, meiosis,
      and cell division. The predicted product of the REC1 gene is a polypeptide of 522
      amino acid residues with a molecular mass of 56,866 daltons, with no overall
      sequence homology to any other known protein. The open reading frame of the REC1
      gene placed by itself in a U. maydis expression vector was found to be sufficient
      to complement the rec1 mutant. Overexpression of REC1 in Escherichia coli gave
      rise to the anticipated 57-kDa product together with a 3'-->5' exonuclease
      activity. This activity was only present in cells overexpressing REC1 and its
      characteristics were distinguishable from the major bacterial nucleases, but it
      had certain enzymatic features in common with epsilon, the proofreading
      exonuclease subunit of E. coli DNA polymerase III holoenzyme. To facilitate
      isolation of the protein product from bacteria, the REC1 gene was overexpressed
      from a vector that fused a hexa-histidine-leader sequence onto the amino
      terminus, enabling the isolation of the HisREC1 product on an immobilized metal
      ion affinity column. The His-REC1 protein co-eluted with the novel exonuclease
      activity. Alignment of the amino acid sequence of the REC1 gene product with the
      conserved proofreading exonuclease motifs of DNA polymerases indicated
      significant homology.

PMID- 8276879
TI  - Characterization and crystallization of recombinant human neurotrophin-4.
AB  - Neurotrophin-4 (NT-4) is the most recently discovered member of the neurotrophin
      family. We have expressed, refolded, and purified recombinant human NT-4 from
      Escherichia coli and compared it with recombinant human NT-4 secreted into the
      culture medium of baculovirus-infected insect cells. Both preparations were
      characterized and determined to be indistinguishable according to several
      biochemical criteria. Recombinant NT-4 from E. coli was crystallized in a form
      suitable for x-ray analysis, and characterization of these crystals indicated
      that NT-4 was present as a dimer within the asymmetric unit. NT-4 was active in
      promoting the survival of rat TrkB receptor-expressing fibroblasts, but was
      inactive on embryonic chicken sensory neurons, unlike the other members of the
      neurotrophin family and in contrast to the reported activities of partially
      purified NT-4.

PMID- 8276880
TI  - Regulation of neural cell adhesion molecule and L1 by the transforming growth
      factor-beta superfamily. Selective effects of the bone morphogenetic proteins.
AB  - The transforming growth factor-beta (TGF-beta) superfamily plays a role in
      embryogenesis and regeneration. We have reported that osteogenic protein-1 (OP-1)
      promotes cell aggregation and induces the expression of the neural cell adhesion
      molecules N-CAM and L1 in proliferating neuroblastoma x glioma hybrid NG108-15
      cells (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992)
      Proc. Natl. Acad. Sci. U.S.A. 89, 10326-10330; Perides, G., Hu, G., Rueger, D.
      C., and Charness, M. E. (1993) J. Biol. Chem. 268, 25197-25205). Here we show
      that the structurally homologous bone morphogenetic proteins (BMP) BMP-2 and BMP
      4 are 10-50-fold more potent in these actions than the subfamily comprising BMP
      5, BMP-6, and OP-1 (BMP-7). In contrast, members of the TGF-beta subfamily,
      activin-A, inhibin-A, and 29 additional growth factors and cytokines did not
      induce N-CAM. The addition of serum to cells growing in serum-free medium caused
      a concentration-dependent increase in N-CAM and L1 expression; however, serum did
      not potentiate the induction of N-CAM and L1 by 40 ng/ml OP-1. These findings
      suggest the presence in NG108-15 cells of a BMP-2/BMP-4 receptor that
      discriminates subtle differences in structure among homologous members of the TGF
      beta superfamily. An endogenous ligand for this receptor may be present in serum.

PMID- 8276881
TI  - Regulation of interleukin-8 expression in porcine alveolar macrophages by
      bacterial lipopolysaccharide.
AB  - Interleukin (IL)-8 is a macrophage-derived neutrophil chemotactic factor that
      plays an important role in the recruitment of neutrophils to inflammatory loci.
      Hence, expression of IL-8 by alveolar macrophages may be a significant factor in
      host defense in the lung and in the pathogenesis of pneumonia in swine. To
      initiate molecular studies of IL-8 regulation in pigs, we cloned IL-8 cDNA and
      examined the regulation of its mRNA in alveolar macrophages. The porcine IL-8
      cDNA consists of 1491 base pairs including a coding region of 309 base pairs. The
      deduced amino acid sequence was 75 and 81% similar to human and rabbit IL-8,
      respectively. Resting macrophages contained low levels of IL-8 mRNA, which
      increased markedly after exposure to bacterial lipopolysaccharide (LPS). LPS
      induction of IL-8 was direct, not mediated through elevation of tumor necrosis
      factor or interleukin-1. The effect of LPS on IL-8 expression was dose dependent,
      and induction was observed at a concentration of 10 pg/ml. IL-8 mRNA expression
      was detectable within 0.5 h after stimulation with LPS, peaked at 3-6 h at about
      30-fold higher levels than in resting cells, and was maintained for 24 h.
      Secreted IL-8, measured by neutrophil chemotaxis, was induced within 4 h by LPS,
      and accumulated in the media throughout the 24-h period. The mechanism of
      induction of IL-8 mRNA appeared to involve transcription and RNA processing.
      Nuclear run-on analysis showed that the IL-8 gene was actively transcribed in
      noninduced cells; upon stimulation with LPS, the rate of IL-8 transcription was
      increased about 4-fold. A single mature mRNA species was detected by primer
      extension analysis. The half-life of IL-8 mRNA transcripts in aveolar macrophages
      was approximately 2 h and did not change after LPS stimulation. The ability of
      LPS to induce IL-8 expression was suppressed by recombinant human IL-4 and
      dexamethasone in a concentration-dependent manner. These observations indicate
      that the expression of IL-8 is an early event in the sequelae to bacterial
      infection in the lung.

PMID- 8276882
TI  - Energy-dependent protein-triacylglycerol interaction in a cell-free system from
      3T3-L1 adipocytes.
AB  - Triacylglycerol is synthesized from the precursors sn-1,2-diacylglycerol and and
      palmitoyl-CoA in a reaction catalyzed by the microsomal enzyme diacylglycerol
      acyltransferase (EC 2.3.1.20). Isolated 3T3-L1 adipocyte microsomal vesicles from
      cells pulse-labeled with L-[35S]methionine were found to release microsomal
      proteins into a low density form during the synthesis of triacylglycerol. The
      proteins released, which represent a subset of those present in the labeled
      microsomes, include a 62-kDa protein found in high concentration in mature fat
      droplets. The formation of the triacylglycerol-protein complexes was dependent on
      time and temperature, was not stimulated by cytosol, and required ATP as well as
      diacylglycerol and palmitoyl-CoA. Only nucleoside triphosphates and not non
      hydrolyzable analogues could replace ATP in the reaction. Unlike the enzyme
      reaction that measures the synthesis of triacylglycerol, the formation of low
      density membrane is thus dependent on ATP hydrolysis as well as enzyme
      substrates. The newly formed, low density particles are selectively enriched in
      triacylglycerol synthesized during the reaction as well as that synthesized prior
      to the reaction. The cell-free system described thus appears to represent an
      early adipogenic event leading to the lipid vacuoles found in mature adipocytes.

PMID- 8276883
TI  - Development of a human interleukin-6 receptor antagonist.
AB  - Neutralizing monoclonal antibodies specific for human interleukin-6 (IL-6) bind
      two distinct sites on the IL-6 protein (sites I and II). Their interference with
      IL-6 receptor binding suggested that site I is a receptor-binding site of IL-6,
      whereas site II is important for signal transduction. Mutagenesis of site II
      could therefore result in the isolation of IL-6 receptor antagonists. To test
      this hypothesis, a panel of IL-6 mutant proteins was constructed that did not
      bind to a site II-specific monoclonal antibody. One such site II mutant protein
      (with double substitution of Gln-160 with Glu and Thr-163 with Pro) was found to
      be an antagonist of human IL-6. It was inactive on human CESS cells, weakly
      active on human HepG2 cells, but active on mouse B9 cells. It could specifically
      antagonize the activity of wild-type IL-6 on CESS and HepG2 cells. The binding
      affinity of this variant for the 80-kDa IL-6 receptor was similar to that of wild
      type IL-6. High affinity binding to CESS cells, however, was abolished,
      suggesting that the mutant protein is inactive because the complex of the 80-kDa
      IL-6 receptor and the mutant protein cannot associate with the signal transducer
      gp130. The human IL-6 antagonist protein may be potentially useful as a
      therapeutic agent.

PMID- 8276884
TI  - Expression cloning of an insect diuretic hormone receptor. A member of the
      calcitonin/secretin receptor family.
AB  - Insect diuretic hormones and their receptors regulate fluid and ion secretion and
      thus are attractive targets for the design of novel insect control agents. A
      complementary DNA clone encoding a corticotropin-releasing factor-related
      diuretic hormone receptor from the tobacco hornworm Manduca sexta was isolated by
      expression cloning in COS-7 cells. The receptor consists of 395 amino acids and
      contains seven putative transmembrane domains. The expressed receptor binds M.
      sexta diuretic hormone, as well as several related insect diuretic peptides with
      high affinity. Furthermore, each of these peptides stimulate adenylate cyclase in
      COS-7 cells transfected with the receptor. The M. sexta diuretic hormone receptor
      is homologous to the receptors for calcitonin, secretin, vasoactive intestinal
      peptide, parathyroid hormone, glucagon-like peptide 1, growth hormone-releasing
      hormone, pituitary adenylate cyclase-activating polypeptide, and glucagon. The M.
      sexta diuretic hormone receptor is the first nonmammalian member of this family
      to be identified.

PMID- 8276885
TI  - Breaking through the tight junction barrier.

PMID- 8276886
TI  - SMC1: an essential yeast gene encoding a putative head-rod-tail protein is
      required for nuclear division and defines a new ubiquitous protein family.
AB  - The smc1-1 mutant was identified initially as a mutant of Saccharomyces
      cerevisiae that had an elevated rate of minichromosome nondisjunction. We have
      cloned the wild-type SMC1 gene. The sequence of the SMC1 gene predicts that its
      product (Smc1p) is a 141-kD protein, and antibodies against Smc1 protein detect a
      protein with mobility of 165 kD. Analysis of the primary and putative secondary
      structure of Smc1p suggests that it contains two central coiled-coil regions
      flanked by an amino-terminal nucleoside triphosphate (NTP)-binding head and a
      conserved carboxy-terminal tail. These analyses also indicate that Smc1p is an
      evolutionary conserved protein and is a member of a new family of proteins
      ubiquitous among prokaryotes and eukaryotes. The SMC1 gene is essential for
      viability. Several phenotypic characteristics of the mutant alleles of smc1 gene
      indicate that its product is involved in some aspects of nuclear metabolism, most
      likely in chromosome segregation. The smc1-1 and smc1-2 mutants have a dramatic
      increase in mitotic loss of a chromosome fragment and chromosome III,
      respectively, but have no increase in mitotic recombination. Depletion of SMC1
      function in the ts mutant, smc1-2, causes a dramatic mitosis-related lethality.
      Smc1p-depleted cells have a defect in nuclear division as evidenced by the
      absence of anaphase cells. This phenotype of the smc1-2 mutant is not RAD9
      dependent. Based upon the facts that Smc1p is a member of a ubiquitous family,
      and it is essential for yeast nuclear division, we propose that Smc1p and Smc1p
      like proteins function in a fundamental aspect of prokaryotic and eukaryotic cell
      division.

PMID- 8276887
TI  - Inhibition of nuclear protein import by nonhydrolyzable analogues of GTP and
      identification of the small GTPase Ran/TC4 as an essential transport factor.
AB  - We have investigated a possible involvement of GTPases in nuclear protein import
      using an in vitro transport system involving digitonin-permeabilized cells
      supplemented with exogenous cytosol. Transport in this system was measured with a
      novel ELISA-based assay that allows rapid quantitative analysis. GTP gamma S and
      other nonhydrolyzable analogues of GTP were found to rapidly inhibit the rate of
      in vitro nuclear import. Transport inhibition by GTP gamma S was dependent on the
      concentrations of permeabilized cells and cytosol, and was strongly enhanced by a
      cytosolic factor(s). The predominant cytosolic component responsible for this
      inhibition was found in a 20-30-kD fraction in molecular sieving chromatography.
      Furthermore, a component(s) of this 20-30-kD fraction was itself required for
      efficient nuclear import. Biochemical complementation with bacterially expressed
      protein demonstrated that this essential GTP gamma S-sensitive transport factor
      was Ran/TC4, a previously described GTPase of the Ras superfamily found in both
      nucleus and cytoplasm. Ran/TC4 and its guanine nucleotide release protein RCC1
      have previously been implicated in DNA replication, cell cycle checkpoint
      control, and RNA synthesis, processing and export. Our results suggest that
      Ran/TC4 serves to integrate nuclear protein import with these other nuclear
      activities.

PMID- 8276888
TI  - The role of CaaX-dependent modifications in membrane association of Xenopus
      nuclear lamin B3 during meiosis and the fate of B3 in transfected mitotic cells.
AB  - Recent evidence shows that the COOH-terminal CaaX motif of lamins is necessary to
      target newly synthesized proteins to the nuclear envelope membranes.
      Isoprenylation at the CaaX-cysteine has been taken to explain the different fates
      of A- and B-type lamins during cell division. A-type lamins, which loose their
      isoprenylation shortly after incorporation into the lamina structure, become
      freely soluble upon mitotic nuclear envelope breakdown. Somatic B-type lamins, in
      contrast, are permanently isoprenylated and, although depolymerized during
      mitosis, remain associated with remnants of nuclear envelope membranes. However,
      Xenopus lamin B3, the major B-type lamin of amphibian oocytes and eggs, becomes
      soluble after nuclear envelope breakdown in meiotic metaphase. Here we show that
      Xenopus lamin B3 is permanently isoprenylated and carboxyl methylated in oocytes
      (interphase) and eggs (meiotic metaphase). When transfected into mouse L cells
      Xenopus lamin B3 is integrated into the host lamina and responds to cell cycle
      signals in a normal fashion. Notably, the ectopically expressed Xenopus lamin
      does not form heterooligomers with the endogenous lamins as revealed by a
      coprecipitation experiment with mitotic lamins. In contrast to the situation in
      amphibian eggs, a significant portion of lamin B3 remains associated with
      membranes during mitosis. We conclude from these data that the CaaX motif
      mediated modifications, although necessary, are not sufficient for a stable
      association of lamins with membranes and that additional factors are involved in
      lamin-membrane binding.

PMID- 8276889
TI  - Lamin B distribution and association with peripheral chromatin revealed by
      optical sectioning and electron microscopy tomography.
AB  - We have used a combination of immunogold staining, optical sectioning light
      microscopy, intermediate voltage electron microscopy, and EM tomography to
      examine the distribution of lamin B over the nuclear envelope of CHO cells.
      Apparent inconsistencies between previously published light and electron
      microscopy studies of nuclear lamin staining were resolved. At light microscopy
      resolution, an apparent open fibrillar network is visualized. Colocalization of
      lamin B and nuclear pores demonstrates that these apparent fibrils, separated by
      roughly 0.5 micron, are anti-correlated with the surface distribution of nuclear
      pores; pore clusters lie between or adjacent to regions of heavy lamin B
      staining. Examination at higher, EM resolution reveals that this apparent lamin B
      network does not correspond to an actual network of widely spaced, discrete
      bundles of lamin filaments. Rather it reflects a quantitative variation in lamin
      staining over a roughly 0.5-micron size scale, superimposed on a more continuous
      but still complex distribution of lamin filaments, spatially heterogeneous on a
      0.1-0.2-micron size scale. Interestingly, lamin B staining at this higher
      resolution is highly correlated to the underlying chromatin distribution. Heavy
      concentrations of lamin B directly "cap" the surface of envelope associated,
      large-scale chromatin domains.

PMID- 8276890
TI  - GLUT2 surface expression and intracellular transport via the constitutive pathway
      in pancreatic beta cells and insulinoma: evidence for a block in trans-Golgi
      network exit by brefeldin A.
AB  - The biosynthesis, intracellular transport, and surface expression of the beta
      cell glucose transporter GLUT2 was investigated in isolated islets and insulinoma
      cells. Using a trypsin sensitivity assay to measure cell surface expression, we
      determined that: (a) greater than 95% of GLUT2 was expressed on the plasma
      membrane; (b) GLUT2 did not recycle in intracellular vesicles; and (c) after
      trypsin treatment, reexpression of the intact transporter occurred with a t1/2 of
      approximately 7 h. Kinetics of intracellular transport of GLUT2 was investigated
      in pulse-labeling experiments combined with glycosidase treatment and the trypsin
      sensitivity assay. We determined that transport from the endoplasmic reticulum to
      the trans-Golgi network (TGN) occurred with a t1/2 of 15 min and that transport
      from the TGN to the plasma membrane required a similar half-time. When added at
      the start of a pulse-labeling experiment, brefeldin A prevented exit of GLUT2
      from the endoplasmic reticulum. When the transporter was first accumulated in the
      TGN during a 15-min period of chase, but not following a low temperature (22
      degrees C) incubation, addition of brefeldin A (BFA) prevented subsequent surface
      expression of the transporter. This indicated that brefeldin A prevented GLUT2
      exit from the TGN by acting at a site proximal to the 22 degrees C block.
      Together, these data demonstrate that GLUT2 surface expression in beta cells is
      via the constitutive pathway, that transport can be blocked by BFA at two
      distinct steps and that once on the surface, GLUT2 does not recycle in
      intracellular vesicles.

PMID- 8276891
TI  - Clathrin facilitates the internalization of seven transmembrane segment receptors
      for mating pheromones in yeast.
AB  - The role of clathrin in endocytosis of the yeast phermone receptors was examined
      using strains expressing a temperature-sensitive clathrin heavy chain. The yeast
      phermone receptors belong to the family of seven transmembrane segment, G-protein
      coupled receptors. A rapid and reversible defect in uptake of radiolabeled alpha
      factor pheromone occurred when the cells were transferred to the nonpermissive
      temperature. Constitutive, pheromone-independent internalization of newly
      synthesized a-factor phermone receptor was also rapidly inhibited in mutant
      strains at the nonpermissive temperature. In both cases residual endocytosis, 30
      50% of wild-type levels, was detected in the absence of functional clathrin heavy
      chain. Once internalized, the a-factor receptor was delivered to the vacuole at
      comparable rates in chc1-ts and wild-type cells at the nonpermissive temperature.
      Clathrin heavy chain was also required for maximal uptake of a mutant a-factor
      receptor which is dependent on pheromone for internalization. In the presence of
      a-factor, the internalization rate of the mutant receptor in chc1-ts cells at the
      nonpermissive temperature was 2.5 times slower than the rate observed for
      endocytosis of the mutant receptor in wild-type cells. These experiments provide
      in vivo evidence that clathrin plays an important role in the endocytosis of the
      seven trans-membrane segment pheromone receptors in yeast.

PMID- 8276892
TI  - In vitro insertion of the 22-kD peroxisomal membrane protein into isolated rat
      liver peroxisomes.
AB  - The membrane insertion of the 22-kD integral peroxisomal membrane protein (PMP
      22) was studied in a system in which peroxisomes isolated from rat liver were
      incubated with the [35S]methionine-labeled in vitro translation product of PMP 22
      mRNA. Membrane insertion of PMP 22 was demonstrated by protease treatment of
      peroxisomes in the absence and presence of detergent. Approximately 35% of total
      in vitro translated PMP 22 became protease resistant after a 1-h incubation at 26
      degrees C. Import was dependent on time and temperature, did not require ATP or
      GTP and was not inhibited by N-ethylmaleimide treatment of neither the soluble
      components of the translation mixture nor of the isolated peroxisomes. In
      contrast to these results it was recently shown that the import of the
      peroxisomal marker, firefly luciferase, into peroxisomes of permeabilized cells
      was dependent on ATP hydrolysis and was blocked by N-ethylmaleimide pretreatment
      of the cytosol-depleted cells (Rapp et al., 1993; Wendland and Subramani, 1993).
      Therefore, the present data suggest that insertion of PMP 22 into the peroxisomal
      membrane and translocation of firefly luciferase into peroxisomes follow distinct
      mechanisms. At low temperature binding of PMP 22 to the peroxisomal membrane was
      not influenced whereas insertion was strongly inhibited. Pretreatment of
      peroxisomes with subtilisin reduced binding to a low level and completely
      abolished insertion. Therefore it is suggested that binding is prerequisite to
      insertion and that insertion may be mediated by a proteinaceous receptor.

PMID- 8276893
TI  - zeta-COP, a subunit of coatomer, is required for COP-coated vesicle assembly.
AB  - cDNA encoding the 20-kD subunit of coatomer, zeta-COP, predicts a protein of 177
      amino acid residues, similar in sequence to AP17 and AP19, subunits of the
      clathrin adaptor complexes. Polyclonal antibody directed to zeta-COP blocks the
      binding of coatomer to Golgi membranes and prevents the assembly of COP-coated
      vesicles on Golgi cisternae. Unlike other coatomer subunits (beta-, beta'-, gamma
      , and epsilon-COP), zeta-COP exists in both coatomer bound and free pools.

PMID- 8276894
TI  - Two pathways for the degradation of the H2 subunit of the asialoglycoprotein
      receptor in the endoplasmic reticulum.
AB  - An intermediate of 35 kD accumulates transiently during ER degradation of the H2
      subunit of the asialoglycoprotein receptor; it is derived by an endoproteolytic
      cleavage in the exoplasmic domain near the transmembrane region. In the presence
      of cycloheximide all of the precursor H2 is converted to this intermediate, which
      is degraded only after cycloheximide is removed (Wikstrom, L., and H. F. Lodish.
      1991. J. Cell Biol. 113:997-1007). Here we have generated mutants of H2 that do
      not form the 35-kD fragment, either in transfected cells or during in vitro
      translation reactions in the presence of pancreatic microsomes. In transfected
      cells the kinetics of ER degradation of these mutant proteins are
      indistinguishable from that of wild-type H2, indicating the existence of a second
      pathway of ER degradation which does not involve formation of the 35-kD fragment.
      Degradation of H2 in the ER by this alternative pathway is inhibited by TLCK or
      TPCK, but neither formation nor degradation of the 35-kD fragment is blocked by
      these reagents. As determined by NH2-terminal sequencing of the 35-kD fragment,
      formed either in transfected cells or during in vitro translation reactions in
      the presence of pancreatic microsomes, the putative cleavage sites are between
      small polar, uncharged amino acid residues. Substitution of the residues NH2- or
      COOH-terminal to the cleavage site by large hydrophobic or charged ones decreased
      the amount of 35-kD fragment formed and in some cases changed the putative
      cleavage site. Cleavage can also be affected by amino acid substitutions (e.g.,
      to proline or glycine) which change protein conformation. Therefore, the
      endoprotease that generates the 35-kD fragment has specificity similar to that of
      signal peptidase. H2a and H2b are isoforms that differ only by a pentapeptide
      insertion in the exoplasmic juxtamembrane region of H2a. 100% of H2a is degraded
      in the ER, but up to 30% of H2b folds properly and matures to the cell surface.
      The sites of cleavage to form the 35-kD fragment are slightly different in H2a
      and H2b. Two mutant H2b proteins, with either a glycine or proline substitution
      at the position of insertion of the pentapeptide in H2a, have metabolic fates
      similar to that of H2a. These mutations are likely to change the protein
      conformation in this region. Thus the conformation of the juxtamembrane domain of
      the H2 protein is important in determining its metabolic fate within the ER.

PMID- 8276895
TI  - Role of the transmembrane and extracytoplasmic domain of beta subunits in subunit
      assembly, intracellular transport, and functional expression of Na,K-pumps.
AB  - The ubiquitous Na,K- and the gastric H,K-pumps are heterodimeric plasma membrane
      proteins composed of an alpha and a beta subunit. The H,K-ATPase beta subunit
      (beta HK) can partially act as a surrogate for the Na,K-ATPase beta subunit (beta
      NK) in the formation of functional Na,K-pumps (Horisberger et al., 1991. J. Biol.
      Chem. 257:10338-10343). We have examined the role of the transmembrane and/or the
      ectodomain of beta NK in (a) its ER retention in the absence of concomitant
      synthesis of Na,K-ATPase alpha subunits (alpha NK) and (b) the functional
      expression of Na,K-pumps at the cell surface and their activation by external K+.
      We have constructed chimeric proteins between Xenopus beta NK and rabbit beta HK
      by exchanging their NH2-terminal plus transmembrane domain with their COOH
      terminal ectodomain (beta NK/HK, beta HK/NK). We have expressed these constructs
      with or without coexpression of alpha NK in the Xenopus oocyte. In the absence of
      alpha NK, Xenopus beta NK and all chimera that contained the ectodomain of beta
      NK were retained in the ER while beta HK and all chimera with the ectodomain of
      beta HK could leave the ER suggesting that ER retention of unassembled Xenopus
      beta NK is mediated by a retention signal in the ectodomain. When coexpressed
      with alpha NK, only beta NK and beta NK/HK chimera assembled efficiently with
      alpha NK leading to similar high expression of functional Na,K-pumps at the cell
      surface that exhibited, however, a different apparent K+ affinity. beta HK or
      chimera with the transmembrane domain of beta HK assembled less efficiently with
      alpha NK leading to lower expression of functional Na,K-pumps with a different
      apparent K+ affinity. The data indicate that the transmembrane domain of beta NK
      is important for efficient assembly with alpha NK and that both the transmembrane
      and the ectodomain of beta subunits play a role in modulating the transport
      activity of Na,K-pumps.

PMID- 8276896
TI  - Occludin: a novel integral membrane protein localizing at tight junctions.
AB  - Recently, we found that ZO-1, a tight junction-associated protein, was
      concentrated in the so called isolated adherens junction fraction from the liver
      (Itoh, M., A. Nagafuchi, S. Yonemura, T. Kitani-Yasuda, Sa. Tsukita, and Sh.
      Tsukita. 1993. J. Cell Biol. 121:491-502). Using this fraction derived from chick
      liver as an antigen, we obtained three monoclonal antibodies specific for a
      approximately 65-kD protein in rats. This antigen was not extractable from plasma
      membranes without detergent, suggesting that it is an integral membrane protein.
      Immunofluorescence and immunoelectron microscopy with these mAbs showed that this
      approximately 65-kD membrane protein was exclusively localized at tight junctions
      of both epithelial and endothelial cells: at the electron microscopic level, the
      labels were detected directly over the points of membrane contact in tight
      junctions. To further clarify the nature and structure of this membrane protein,
      we cloned and sequenced its cDNA. We found that the cDNA encoded a 504-amino acid
      polypeptide with 55.9 kDa. A search of the data base identified no proteins with
      significant homology to this membrane protein. A most striking feature of its
      primary structure was revealed by a hydrophilicity plot: four putative membrane
      spanning segments were included in the NH2-terminal half. This hydrophilicity
      plot was very similar to that of connexin, an integral membrane protein in gap
      junctions. These findings revealed that an integral membrane protein localizing
      at tight junctions is now identified, which we designated as "occludin."

PMID- 8276897
TI  - Activation of actin polymerization by phosphatidic acid derived from
      phosphatidylcholine in IIC9 fibroblasts.
AB  - alpha-Thrombin induced a change in the cell morphology of IIC9 fibroblasts from a
      semiround to an elongated form, accompanied by an increase in stress fibers.
      Incubation of the cells with phospholipase D (PLD) from Streptomyces chromofuscus
      and exogenous phosphatidic acid (PA) caused similar morphological changes,
      whereas platelet-derived growth factor (PDGF) and phorbol 12-myristate 13-acetate
      (PMA) induced different changes, e.g., disruption of stress fibers and cell
      rounding. alpha-Thrombin, PDGF, and exogenous PLD increased PA by 20-40%, and PMA
      produced a smaller increase. alpha-Thrombin and exogenous PLD produced rapid
      increases in the amount of filamentous actin (F-actin) that were sustained for at
      least 60 min. However, PDGF produced a transient increase of F-actin at 1 min and
      PMA caused no significant change. Dioctanoylglycerol was ineffective except at 50
      micrograms/ml. Phospholipase C from Bacillus cereus, which increased
      diacylglycerol (DAG) but not PA, did not change F-actin content. Down-regulation
      of protein kinase C (PKC) did not block actin polymerization induced by alpha
      thrombin. H-7 was also ineffective. Exogenous PA activated actin polymerization
      with a significant effect at 0.01 microgram/ml and a maximal increase at 1
      microgram/ml. No other phospholipids tested, including polyphosphoinositides,
      significantly activated actin polymerization. PDGF partially inhibited PA-induced
      actin polymerization after an initial increase at 1 min. PMA completely or
      largely blocked actin polymerization induced by PA or PLD. These results show
      that PC-derived PA, but not DAG or PKC, activates actin polymerization in IIC9
      fibroblasts, and indicate that PDGF and PMA have inhibitory effects on PA-induced
      actin polymerization.

PMID- 8276898
TI  - Cell shape and interaction defects in alpha-spectrin mutants of Drosophila
      melanogaster.
AB  - We show that the alpha-spectrin gene is essential for larval survival and
      development by characterizing several alpha-spectrin mutations in Drosophila. P
      element minigene rescue and sequence analysis were used to identify the alpha
      spectrin gene as the l(3)dre3 complementation group of the Dras-Roughened
      ecdysoneless region of chromosome 3 (Sliter et al., 1988). Germ line
      transformants carrying an alpha-spectrin cDNA, whose expression is driven by the
      ubiquitin promoter, fully rescued the first to second instar lethality
      characteristic of the l(3)dre3 alleles. The molecular defects in two gamma-ray
      induced alleles were identified. One of these mutations, which resulted in second
      instar lethality, contained a 73-bp deletion in alpha-spectrin segment 22
      (starting at amino acid residue 2312), producing a premature stop codon between
      the two EF hands found in this segment. The second mutation, which resulted in
      first instar lethality, contained a 20 base pair deletion in the middle of
      segment 1 (at amino acid residue 92), resulting in a premature stop codon.
      Examination of the spectrin-deficient larvae revealed a loss of contact between
      epithelial cells of the gut and disruption of cell-substratum interactions. The
      most pronounced morphological change was seen in tissues of complex cellular
      architecture such as the middle midgut where a loss of cell contact between cup
      shaped cuprophilic cells and neighboring interstitial cells was accompanied by
      disorganization of the cuprophilic cell brush borders. Our examination of
      spectrin deficient larvae suggests that an important role of non-erythroid
      spectrin is to stabilize cell to cell interactions that are critical for the
      maintenance of cell shape and subcellular organization within tissues.

PMID- 8276899
TI  - Microtubule-dependent control of cell shape and pseudopodial activity is
      inhibited by the antibody to kinesin motor domain.
AB  - One of the major functions of cytoplasmic microtubules is their involvement in
      maintenance of asymmetric cell shape. Microtubules were considered to perform
      this function working as rigid structural elements. At the same time,
      microtubules play a critical role in intracellular organelle transport, and this
      fact raises the possibility that the involvement of microtubules in maintenance
      of cell shape may be mediated by directed transport of certain cellular
      components to a limited area of the cell surface (e.g., to the leading edge)
      rather than by their functioning as a mechanical support. To test this hypothesis
      we microinjected cultured human fibroblasts with the antibody (called HD
      antibody) raised against kinesin motor domain highly conserved among the
      different members of kinesin superfamily. As was shown before this antibody
      inhibits kinesin-dependent microtubule gliding in vitro and interferes with a
      number of microtubule-dependent transport processes in living cells. Preimmune
      IgG fraction was used for control experiments. Injections of fibroblasts with HD
      antibody but not with preimmune IgG significantly reduced their asymmetry,
      resulting in loss of long processes and elongated cell shape. In addition,
      antibody injection suppressed pseudopodial activity at the leading edge of
      fibroblasts moving into an experimentally made wound. Analysis of membrane
      organelle distribution showed that kinesin antibody induced clustering of
      mitochondria in perinuclear region and their withdrawal from peripheral parts of
      the cytoplasm. HD antibody does not affect either density or distribution of
      cytoplasmic microtubules. The results of our experiments show that many changes
      of phenotype induced in cells by microtubule-depolymerizing agents can be
      mimicked by the inhibition of motor proteins, and therefore microtubule functions
      in maintaining of the cell shape and polarity are mediated by motor proteins
      rather than by being provided by rigidity of tubulin polymer itself.

PMID- 8276900
TI  - The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in
      Saccharomyces cerevisiae.
AB  - Bud emergence, spindle pole body duplication and DNA replication are all
      dependent on the activation of the CDC28 protein kinase at the Start point in the
      G1 phase of the cell cycle. Bud emergence requires polarization of the
      cytoskeleton and secretory vesicles to a specific site on the cell surface.
      Cdc28p activated by G1-cyclins triggers polarization of actin to the site of bud
      emergence and favors apical bud growth (Lew, D. J., and S. I. Reed. 1993. J. Cell
      Biol. 120:1305-1320). We isolated slt2-1 as a mutation that enhances the division
      defect of cdc28 mutants with defects at Start. Slt2p(Mpk1p) is a member of the
      MAP kinase family (Lee, K. S., K. Irie, Y. Gotoh, Y. Watanabe, H. Araki, E.
      Nishida, K. Matsumoto, and D. E. Levin. 1993. Mol. Cell. Biol. 13:3067-3075). We
      show that slt2 mutants exhibit phenotypes similar to those shown by mutants of
      the yeast actin cytoskeleton, including delocalization of chitin deposition and
      of actin cortical spots and the accumulation of secretory pathway membranes and
      vesicles. Furthermore, slt2::HIS3 act1-1 and slt2::HIS3 myo2-66 double mutants
      are inviable. We suggest that Slt2p functions downstream or in parallel with
      Cdc28p in promoting bud formation and apical growth.

PMID- 8276901
TI  - Nerve growth factor regulates the abundance and distribution of K+ channels in
      PC12 cells.
AB  - We examined the effect of nerve growth factor (NGF) treatment on expression of a
      neuronal delayed rectifler K+ channel subtype, Kv2.1 (drk1), in PC12 cells. Anti
      Kv2.1 antibodies recognized a single polypeptide population of M(r) = 132 kD in
      PC12 cell membranes, distinct from the more heterogeneous population found in
      adult rat brain. In response to NGF treatment, levels of Kv2.1 polypeptide in
      PC12 membranes increased fourfold. This increase in polypeptide levels could be
      seen within 12 h, and elevated levels were maintained for at least 6 d of
      continuous NGF treatment. RNase protection assays indicate that this increase in
      Kv2.1 protein occurs without an increase in steady state levels of Kv2.1 mRNA
      following NGF treatment. Immunofluorescent localization of the Kv2.1 polypeptide
      revealed plasma membrane-associated staining of cell bodies in both untreated and
      NGF-treated PC12 cells. In undifferentiated cells, intense staining is seen at
      sites of cell-cell and cell-substratum contact. In differentiated cells the most
      intense Kv2.1 staining is observed in neuritic growth cones. These studies show
      that in PC12 cells both the abundance and distribution of the Kv2.1 k+ channel
      are regulated by NGF, and suggest that PC12 cells provide a model for the
      selective expression of Kv2.1 in neuritic endings.

PMID- 8276902
TI  - Interactions of synapsin I with phospholipids: possible role in synaptic vesicle
      clustering and in the maintenance of bilayer structures.
AB  - Synapsin I is a synaptic vesicle-specific phosphoprotein composed of a globular
      and hydrophobic head and of a proline-rich, elongated and basic tail. Synapsin I
      binds with high affinity to phospholipid and protein components of synaptic
      vesicles. The head region of the protein has a very high surface activity,
      strongly interacts with acidic phospholipids and penetrates the hydrophobic core
      of the vesicle membrane. In the present paper, we have investigated the possible
      functional effects of the interaction between synapsin I and vesicle
      phospholipids. Synapsin I enhances both the rate and the extent of Ca(2+)
      dependent membrane fusion, although it has no detectable fusogenic activity per
      se. This effect, which appears to be independent of synapsin I phosphorylation
      and localized to the head region of the protein, is attributable to aggregation
      of adjacent vesicles. The facilitation of Ca(2+)-induced liposome fusion is
      maximal at 50-80% of vesicle saturation and then decreases steeply, whereas
      vesicle aggregation does not show this biphasic behavior. Association of synapsin
      I with phospholipid bilayers does not induce membrane destabilization. Rather,
      31P-nuclear magnetic resonance spectroscopy demonstrated that synapsin I inhibits
      the transition of membrane phospholipids from the bilayer (L alpha) to the
      inverted hexagonal (HII) phase induced either by increases in temperature or by
      Ca2+. These properties might contribute to the remarkable selectivity of the
      fusion of synaptic vesicles with the presynaptic plasma membrane during
      exocytosis.

PMID- 8276903
TI  - Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E
      cadherin and increased cellular adhesion.
AB  - The Wnt-1 gene plays an essential role in fetal brain development and encodes a
      secreted protein whose signaling mechanism is presently unknown. In this report
      we have investigated intracellular mechanisms by which the Wnt-1 gene induces
      morphological changes in PC12 pheochromocytoma cells. PC12 cells expressing Wnt-1
      show increased steady-state levels of the adhesive junction protein plakoglobin,
      and an altered distribution of this protein within the cell. This effect appears
      similar to a modulation of the plakoglobin homolog, Armadillo, that occurs in
      Drosophila embryos in response to the Wnt-1 homolog, wingless (Riggleman, B., P.
      Schedl, and E. Wieschaus. 1990. Cell. 63:549-560). In addition, PC12/Wnt-1 cells
      show elevated expression of E-cadherin and increased calcium-dependent cell-cell
      adhesion. These results imply evolutionary conservation of cellular responses to
      Wnt-1/wingless and indicate that in certain cell types Wnt-1 may act to modulate
      cell adhesion mechanisms.

PMID- 8276905
TI  - The dynamic structure of the pericellular matrix on living cells.
AB  - Although up to several microns thick, the pericellular matrix is an elusive
      structure due to its invisibility with phase contrast or DIC microscopy. This
      matrix, which is readily visualized by the exclusion of large particles such as
      fixed red blood cells is important in embryonic development and in maintenance of
      cartilage. While it is known that the pericellular matrix which surrounds
      chondrocytes and a variety of other cells consists primarily of proteoglycans and
      hyaluronan with the latter binding to cell surface receptors, the macromolecular
      organization is still speculative. The macromolecular organization previously
      could not be determined because of the collapse of the cell coat with
      conventional fixation and dehydration techniques. Until now, there has been no
      way to study the dynamic arrangement of hyaluronan with its aggregated
      proteoglycans on living cells. In this study, the arrangement and mobility of
      hyaluronan-aggrecan complexes were directly observed in the pericellular matrix
      of living cells isolated from bovine articular cartilage. The complexes were
      labeled with 30- to 40-nm colloidal gold conjugated to 5-D-4, an antibody to
      keratan sulfate, and visualized with video-enhanced light microscopy. From our
      observations of the motion of pericellular matrix macromolecules, we report that
      the chondrocyte pericellular matrix is a dynamic structure consisting of
      individual tethered molecular complexes which project outward from the cell
      surface. These complexes undergo restricted rotation or wobbling. When the cells
      were cultured with ascorbic acid, which promotes production of matrix components,
      the size of the cell coat and the position of the gold probes relative to the
      plasma membrane were not changed. However, the rapidity and extent of the
      tethered motion were reduced. Treatment with Streptomyces hyaluronidase removed
      the molecules that displayed the tethered motion. Addition of hyaluronan and
      aggrecan to hyaluronidase-treated cells yielded the same labeling pattern and
      tethered motion observed with native cell coats. To determine if aggrecan was
      responsible for the extended configuration of the complexes, only hyaluronan was
      added to the hyaluronidase-treated cells. The position and mobility of the
      hyaluronan was detected using biotinylated hyaluronan binding region (b-HABR) and
      gold streptavidin. The gold-labeled b-HABR was found only near the cell surface.
      Based on these observations, the hyaluronan-aggrecan complexes composing the cell
      coat are proposed to be extended in a brush-like configuration in an analogous
      manner to that previously described for high density, grafted polymers in good
      solvents.

PMID- 8276906
TI  - [Natural history of postoperative intraperitoneal adhesions. Surely, a question
      of the day].
AB  - Postoperative intraperitoneal adhesions are known to occur after conventional
      surgery. The prospective study that we have performed in 1992 shows that the
      frequency of postoperative intraperitoneal adhesions is very high (93% of
      patients). It is higher than was stated 20 years ago, while so-called
      "spontaneous" adhesions seem to be decreasing. The histological study of
      postoperative intraperitoneal adhesions shows a specific evolution in time and a
      very high frequency of foreign bodies (starch, variably decayed textile fibers)
      (92%). The very great frequency of such foreign bodies in postoperative
      intraperitoneal adhesions, logically involving them in the genesis of this
      condition, may be an argument in favor of the new surgical techniques, especially
      of celioscopy.

PMID- 8276904
TI  - Regulation and activity-dependence of N-cadherin, NCAM isoforms, and polysialic
      acid on chick myotubes during development.
AB  - Muscle development in vivo involves a complex sequence of cell-cell interactions
      in which secondary myotubes first form in association with primary myotubes and
      subsequently separate from them. We show here that during this process N-cadherin
      and the different structural forms of NCAM are regulated in a pattern that
      involves both temporal changes in expression and localization to particular
      regions of the muscle cell surface. In particular, levels of N-cadherin on
      maturing myotubes are decreased, and the form of NCAM synthesized by the muscle
      changes from a transmembrane non-polysialylated to a lipid-linked polysialylated
      membrane protein. Moreover, while NCAM was distributed on all myotube surfaces,
      the polysialyated form of NCAM was restricted to regions of the myotube surface
      that had recently separated from neighboring cells. We previously found that
      blockade of nerve-induced activity by d-Tubocurarine perturbed muscle cell
      interactions, resulting in a failure of myotubes to separate. We now show that
      this activity blockade also alters adhesion molecule expression. First, N
      cadherin was no longer down-regulated in maturing myotubes, and its persistence
      on the surfaces of mature myotubes may partly explain their failure to separate.
      Secondly, the developmental switch from transmembrane to lipid-linked NCAM did
      not occur, and polysialylated NCAM was no longer formed. As the unusual physical
      properties of PSA have been proposed to impede cell-cell interactions, this
      alteration would also be expected to compromise cell separation. Together, these
      results suggest that the regulated expression of both N-cadherin and NCAM
      isoforms including their polysialylation, is an essential mechanism for the
      normal separation of secondary myotubes from primary myotubes.

PMID- 8276907
TI  - [Nodular goiter. Retrospective analysis of 608 cases].
AB  - A retrospective study was carried out on a series of 608 patients, of whom 430
      had undergone partial and 178 total thyroidectomy for single or multinodular
      goitre. Statistical analysis of data for the 532 women (88%) and 76 men (12%),
      mean age 45 and 39 years respectively, included clinical and operative features,
      specific morbidity of the exeresis, incidence of cancer on multinodular goitre
      and the frequency of recurrence of nodular lesions. The men were significantly
      younger at time of diagnosis (p < 0.0006). Bilateral multinodular forms (n = 577)
      and hypofixing lesions (n = 515) predominated. The incidence of unsuspected
      thyroid cancer in the multinodular cases was 3% (15/444). Carcinoma development
      on single nodules in our series during the same period was 8% (n = 15/195), the
      difference being statistically significant (p < 0.02). Mortality was nil and non
      specific morbidity 2% (n = 12/608). No compressive hematoma was reported and
      tracheotomy was never required. A clinically detectable alteration in the voice
      was noted in 10% (n = 67/608), this persisting in 0.5% (n = 3) beyond the 6th
      postoperative month. No significant difference existed between general and vocal
      morbidity as a function of the type of exeresis. Hypocalcemia was observed in 11%
      of patients (n = 67/608), 49% (n = 33/67) being asymptomatic and the anomaly
      spontaneously reversible. Four percent (n = 7/178) were permanent after total
      thyroidectomy (including 15 cancers on multinodular goitre discovered
      fortuitously, 8 of which received lymph node dissection) and 3% (n = 2/68) after
      a "wide" subtotal thyroidectomy.

PMID- 8276908
TI  - [Lumbar hernias in adults. Apropos of 4 cases and review of the literature].
AB  - Lumbar hernias are rare (2% of abdominal wall hernias). Symptomatology consists
      frequently only of an arch formation seen best with the patient sitting and when
      coughing. In adults it is twice as frequent in women and on the left side. Acute
      events, dominated by incarceration of a digestive segment, particularly colic,
      often suggest the diagnosis (10% of cases). Diagnosis is simple when confronted
      with a large hernia, but difficulties arise with those less than 5 cm in
      diameter, often diagnosed as a lipoma or parietal tumor. Conventional radiographs
      and ultrasound images are usually sufficient to establish the correct diagnosis
      and to determine the content of the hernial sac, but computed tomography scans
      can provide data on the exact limits of the defect and allow evaluation of
      possible problems during surgical repair. Rarely congenital (10%), these hernias
      occur either secondary to a violent lumbo-abdomino-pelvic injury (25%) or
      following surgical intervention to the lumbar region (50% of cases). Small
      hernias can be repaired using the direct approach but larger deficits require the
      insertion of a reinforcing non absorbable prosthesis. Long term results, both for
      the 4 cases reported and those published in the literature, were assessed as
      satisfactory.

PMID- 8276909
TI  - [Inflammatory and infectious lesions of the breast. Contribution of
      ultrasonography].
AB  - Non puerperal abscess associated with periductal mastitis assumes increasing
      importance. US is an excellent tool for detection of an abscess cavity, which
      many have a variety of scanographic findings. Mammography may be difficult to
      perform properly because of pain and edema of the breast.

PMID- 8276910
TI  - [Surgical indications in angiomas of the face].
AB  - Hemangiomas are common vascular tumors of children. They always regress. Surgery
      takes place for late sequelae, such as cutaneous scarring and distortion of the
      facial structures. Early surgery is beneficial for the nasal cyrano hemangioma,
      of for some eyelid hemangiomas. Venous malformations need to be manage from
      childhood to adulthood as they slowly worsen. Percutaneous embolization with
      Ethibloc and surgery are performed in order to minimize, or to improve the skin,
      muscle and bone distortion. Arteriovenous malformations are the most dangerous
      vascular anomalies of the face. Superselective arterial embolization prepares the
      surgical excision of the nidus. Difficulties in covering the excised area are
      frequently solved by flaps or cutaneous expansion.

PMID- 8276911
TI  - [Do abuse of nicotine and alcohol have an effect on the incidence of
      postoperative bacterial infections?].
AB  - In a prospective study we evaluated patients with the diagnosis of 1. groin
      hernia (n1 = 57), 2. gall bladder stones (n2 = 80) and 3. carcinoma of the colon
      (n3 = 76). The whole group included 213 patients who underwent clean, clean
      contaminated or contaminated operations. All wound infections and post-operative
      bacterial infections like pneumonia or urinal infection were registered. The
      patients were asked for risk factors at the time of hospitalisation. 7.1% of all
      patients admitted an intake of alcohol of more than 60 g/day and 15.6% of the
      patients smoked more than 20 cigarettes a day. We found a four times higher risk
      to get a postoperative infection for patients with an intake of more than 60 g
      alcohol a day. The rate of infection for smokers of more than 20 cigarettes a day
      is two times higher than for non smokers or persons who smoke less than 20
      cigarettes a day.

PMID- 8276912
TI  - [Treatments of gastroesophageal reflux by laparoscopy].

PMID- 8276913
TI  - [Value of the posterior route in the surgical treatment of popliteal aneurysm].
AB  - The authors report about 4 cases of surgical treatment of popliteal aneurysms
      through a strictly posterior approach. In all cases, the aneurysm was
      asymptomatic and diagnosed during the assessment of a controlateral symptomatic
      popliteal aneurysm that was treated in a conventional manner (exclusion and
      interposition of a femoropopliteal prosthetic tube through a medial approach).
      The procedure is carried out with the patient in ventral decubitus, and it
      consists in a debridement and graft with direct anatomical interposition of a
      straight PTFE tube. The posterior approach has limitations as it does not allow
      craniad extension and applies only to sacciform or short fusiform aneurysms the
      upper pole of which does not extend beyond Hunter's canal. The graft was an 8-mm
      PTFE straight tube in all 4 cases. All patients had a dynamic bilateral control
      angiography made and none of them presented with symptoms. Three conventional
      restorations required later embolectomy for thrombosis of the prosthesis. In our
      opinion, the use of the posterior approach for the surgery of popliteal aneurysm
      is appealing-provided strict criteria (aneurysm size, scheduled surgery,
      prosthesis) are complied with--as it reduces morbidity, restores the anatomical
      course and allows reducing the rate of postoperative thrombosis, thus ensuring
      better long-term patency.

PMID- 8276914
TI  - [Early stenosis of the common hepatic duct after celioscopic cholecystectomy.
      Apropos of a case].

PMID- 8276915
TI  - [Pancreatic metastasis of a Grawitz tumor].

PMID- 8276917
TI  - [Escherichia coli septicemia revealing acute appendicitis. A case].

PMID- 8276916
TI  - [Contribution of imipenem-cilastatin in the treatment of peritonitis: a
      comparative economical analysis in the case of France].

PMID- 8276918
TI  - [Enzymic mechanism and physiological significance of the glycine cleavage
      reaction with special references to its relation to hyperglycinemia].

PMID- 8276919
TI  - [Molecular lesion and pathophysiology of hyperglycinemia (glycine
      encephalopathy)].

PMID- 8276920
TI  - [Biomechanical properties of the acromioclavicular joints].
AB  - The purpose of this study was to investigate the biomechanical properties of the
      cartilagenous element of the acromioclavicular joint. Experimental specimens of
      the distal end of the clavicle were selected from operative excisions from
      patients with acromioclavicular joint dislocation. Dynamic stiffness, tan delta,
      cartilagenous thickness, elastic modulus and creep modulus were measured with a
      Biomechanical Spectrometer. The results were as follows: There was a negative
      correlation between age and values of dynamic stiffness as well as between age
      and the values of elastic modulus. The values of dynamic stiffness, tan delta,
      cartilagenous thickness, elastic modulus and creep modulus correlated
      significantly with the number of days after injury. The values for the anterior
      parts, excluding dynamic stiffness, were markedly higher than those for the other
      parts. Aging of the articular cartilage may be a factor in the lowering of
      dynamic stiffness and elastic modulus. Degenerative change is evidenced by a
      decrease in cartilaginous thickness and a softening of the articular cartilage.
      The anterior part of the articular surface showed good load-relaxation and
      viscoelastic properties. The anterior parts may act as the center of the
      rotational axis of the clavicle and the fulcrum of the horizontal adduction of
      the scapula when the arm is raised.

PMID- 8276921
TI  - [Experimental histopathological studies of renal lesions induced by high- or low
      osmolality contrast media].
AB  - To elucidate the morphological basis of renal lesions due to intravenous
      administration of radiocontrast media, a comparative study was performed by
      injecting contrast media with different properties, such as high-osmolar ionic
      diatrizoate (60% Urografin), low-osmolar ionic ioxaglate (Hexabix 320) and low
      osmolar non-ionic iopamidol (lopamiron 300), via the tail vein of male Wistar
      rats. Physiologic saline was injected in controls. Each contrast media was
      administered singly as a low dose (1 g I/kg), a moderate dose (3 g I/kg) or a
      high dose (9 g I/kg) to three separate groups of rats. In additional groups of
      rats, a high dose of each contrast media (9 mg I/kg) was administered repeatedly
      two or four times. The animals were sacrificed chronologically from 5 minutes to
      30 days after the last administration and their renal tissues were examined by
      light and electron microscopy. The results indicated that the low osmolar
      contrast media is beneficial in decreasing general symptoms, but there are no
      definite differences between high and low osmolar contrast media in the data of
      blood and urine examination after administration. The iodinated contrast media
      with a low or moderate dose does not induce definite histopathological changes of
      the renal tissue, however, with a high dose it causes vacuolization of proximal
      tubular epithelia, although this change recovers within three days. The repeated
      administration of contrast media with a high dose induces severe damage of
      proximal tubular epithelia with prominent vacuolization, appearance of
      intracytoplasmic granular structure and occasional cell necroses. The
      vacuolization appears even in distal and collective tubules and glomerular
      epithelia. Recovery is retarded under this condition. There are no qualitative
      histological differences of renal lesions induced by the three different contrast
      media. In conclusion, either high or low osmolar contrast media induces almost
      the same histological alteration in renal tissues under the same experimental
      conditions. The more the quantitative increase in administered iodinated contrast
      media, the more prominent is the histological impairment of the kidney. The
      degree of renal lesion and its recovery might depend on the dose of iodine rather
      than the osmolality of the contrast media.

PMID- 8276922
TI  - [Septic multiple organ failure and immune system].

PMID- 8276923
TI  - [Endocrine surgery series. 2. Surgical treatment for Graves' disease. Regarding
      preoperative preparation, operative procedure and postoperative management].

PMID- 8276924
TI  - [Acute abdomen in obstetrical and gynecological practice].

PMID- 8276925
TI  - [Rehabilitation for the brain damaged].

PMID- 8276926
TI  - Mnestic performance profile of a bilateral diencephalic infarct patient with
      preserved intelligence and severe amnesic disturbances.
AB  - The case of a patient with above-average intelligence and educational background,
      high motivation, and an approximate IQ-MQ difference of 40 points is documented.
      The patient has been examined repeatedly for nearly a decade. Extensive
      neuroradiological material of his focal bilateral brain damage in the dorsal
      diencephalon is available. A widespread range of cognitive tests was used to
      investigate his actual performance on all relevant aspects of intelligence,
      attention, subjective memory, immediate retention, learning, skill and problem
      solving abilities, concept formation, cognitive flexibility, priming,
      constructional ability, retrograde memory, and long-term retention. The total of
      more than 50 tests included German-language forms of the revised Wechsler Memory
      Scale and of the Rivermead Behavioural Memory Test. The patient's short-term
      memory and attention were, in spite of his advanced years, average or well above
      average. He gave a number of examples of still intact skills and implicit memory
      abilities, though there was no uniformity in his performance on implicit memory
      tests (e.g., with respect to stored vs. new implicit information). He had no
      awareness of his severe anterograde and retrograde amnesia, documented over a
      large range of verbal and figural tests. Taken together, the results from our
      patient confirm the principal dichotomy between declarative and nondeclarative
      mnestic functions, but give evidence for some restrictions as well. They
      furthermore demonstrate that focal diencephalic damage may result in profound
      anterograde and selective retrograde amnesia, especially with respect to data
      based material, and that disconnecting portions of the medial and basolateral
      limbic circuits has devastating consequences on memory.

PMID- 8276927
TI  - Alien hand sign.
AB  - Usage of the term "alien hand sign" is reviewed in 20 published cases. It refers
      to apparently purposeful, upper-extremity movements that the patient reports are
      beyond his/her control. Lesions were found in medial frontal cortex and/or the
      corpus callosum with presentation being unilateral and transient, unless
      bilateral cortical and subcortical structures were involved. There was a high co
      occurrence of speech hesitation, limb dyspraxia, tactile dysnomia, muscle
      weakness, and grasp reflex on the alien side. Five behavioral manifestations of
      alien movement have been described, with grasping movements and intermanual
      conflict being the most common. Two manifestations, exaggerated ataxic
      automatisms and drifting movements, likely represent other types of movement
      disorders. Dysfunction of the supplementary motor area and related structures has
      been implicated, but the exact causal mechanism remains uncertain.

PMID- 8276928
TI  - Detecting the faking of amnesia: performance differences between simulators and
      patients with memory impairment.
AB  - This study attempted to establish criteria for distinguishing patients with
      genuine memory problems from those who are attempting to simulate amnesia. The
      performance of simulators and genuine amnesics was compared under distraction
      conditions in which subjects had to count backwards between presentation and
      recall, and under no-distraction conditions in which the retention interval was
      unfilled. Genuine amnesics performed significantly worse than controls under
      distraction conditions, but did not perform significantly worse than controls
      under no-distraction conditions. However, those attempting to fake amnesia
      performed significantly worse than controls under no-distraction as well as under
      distraction conditions. They also exaggerated the memory deficit overall relative
      to genuine amnesics. It is suggested that these two criteria might be used
      successfully in clinical settings to assist in the detection of simulators.

PMID- 8276929
TI  - Effects of insulin-dependent diabetes on learning and memory efficiency in
      adults.
AB  - Previous work with elderly adults with maturity-onset non-insulin-dependent
      diabetes has demonstrated the presence of significant learning and memory
      deficits which are correlated with the degree of chronic hyperglycemia. This
      study was conducted to examine learning and memory processes in a group of 82
      younger adults (mean age = 33.4 years) with a long history (mean duration = 26.2
      years) of childhood-onset insulin-dependent diabetes. Contrary to expectation,
      diabetic subjects performed as well as a group of 82 age- and SES-matched
      nondiabetic control subjects on all measures of learning and memory. On the other
      hand, they performed significantly worse on measures of psychomotor efficiency,
      with degree of chronic hyperglycemia being the best predictor of psychomotor
      slowing. These findings, together with earlier studies of elderly diabetic
      patients, suggest that specific neural systems within the aging brain may be
      differentially sensitive to the "toxic" effects of chronic hyperglycemia.

PMID- 8276930
TI  - Accelerated forgetting in Alzheimer-type dementia.
AB  - Accelerated forgetting of name-face associations and grocery list items within
      the first hour postpresentation is demonstrated in 80 persons with Alzheimer's
      disease (AD) compared to 80 control subjects matched on age, education, and
      gender. Differences in forgetting which exceeded statistical regression effects
      remained, even when AD and control subjects were matched on rate of acquisition
      during the learning trials of name-face associations. Results are discussed in
      relation to the neuropathology of AD, organic amnestic disorders, and
      methodological factors concerning previous research on forgetting in persons with
      AD.

PMID- 8276931
TI  - Incidental and intentional recall in Parkinson's disease: an account based on
      diminished attentional resources.
AB  - The recall of common objects and their spatial location was examined in 65
      patients with Parkinson's disease (PD) under conditions in which available
      attentional resources were manipulated by secondary task demands. PD patients
      were impaired at item recall particularly under intentional learning conditions
      but were unimpaired at recall of spatial location. These findings were similar in
      newly diagnosed, untreated cases as well as patients who had suffered with the
      disease for an average of 9.6 years. Test performance was not improved by
      levodopa therapy, despite it benefiting motor control, and was not impaired by
      anticholinergic medication. Item recall correlated significantly with other
      memory measures (particularly tasks of working memory) but only weakly with
      indices of physical disability and traditional frontal-lobe measures. Spatial
      recall, by contrast, correlated with memory quotient but no other cognitive
      measure and depression and disease duration failed to correlate significantly
      with performance on either recall task. These results are attributed to a deficit
      in attentional resources in PD that impairs performance most markedly for tasks
      and conditions that make the greatest demands upon effort.

PMID- 8276932
TI  - Neuropsychological deficits in HIV-1 seropositive and seronegative intravenous
      drug users.
AB  - A battery of neuropsychological tests was administered to detoxified HIV-1
      seropositive and seronegative intravenous drug users. There were few problems
      related to administering the test battery to the groups in question. Of the total
      sample, 28% obtained an Halstead-Reitan Impairment Index > .4, indicating central
      nervous system deficits. Both groups performed below comparable normative levels
      on the variables studied. The HIV-1 infection per se could not explain the
      neuropsychological impairment.

PMID- 8276933
TI  - Assessment of intellectual function in dementing disorders: validity of WAIS-R
      short forms for patients with Alzheimer's, Huntington's, and Parkinson's disease.
AB  - While commonly administered in the neuropsychological assessment of dementia, the
      Wechsler Adult Intelligence Scale-Revised (WAIS-R) is excessively long (70-90
      min) and difficult for many patients. The present study examined WAIS-R data from
      patients with clinically distinct dementing disorders, including those with
      Alzheimer's, Huntington's, and Parkinson's disease (N = 148). The profiles of
      performance of these three patient groups across subtests were remarkably
      similar, suggesting that the use of a short form would not result in the loss of
      clinically significant information. The validity of several published short forms
      was reviewed. Although all of these systematically over- or underestimated Full
      Scale IQ for these patients, after a scaling table revision the Kaufman (1990)
      form appears to provide an accurate estimate of IQ. The use of this short form is
      therefore recommended to minimize frustration and fatigue on the part of the
      patient, and to allow the inclusion of other tests critical to the evaluation of
      dementia within a single assessment session.

PMID- 8276934
TI  - Overcoming the right-ear advantage: a study of focused attention in children.
AB  - Several studies indicate that normal right-handed children of various ages show a
      right-ear advantage (REA) for dichotic verbal stimuli even when instructed to
      attend to the left ear. Other evidence, however, suggests that selective
      listening ability begins to develop in early childhood and that children reliably
      can overcome the REA by the age of 8 or 9 years. We used a signal detection
      procedure to address this apparent contradiction. In the first of two
      experiments, 58 children in two age groups (M = 7 and 10 years) were able to
      overcome the REA for dichotic consonant-vowel (CV) stimuli when instructed to
      focus attention on the left ear. Success in detecting and localizing signals from
      the left ear, as reflected in hit rates, was independent of age and reading
      level. A second experiment, in which strings of dichotic monosyllabic words were
      presented to 56 children at the same two age levels, yielded similar results.
      These findings challenge the claim that ability to overcome the REA when
      attending to the left ear reflects an abnormality of cerebral functioning.

PMID- 8276935
TI  - The diagnostic utility of savings scores: differentiating Alzheimer's and
      Huntington's diseases with the logical memory and visual reproduction tests.
AB  - Recent research has demonstrated that patients with dementia of the Alzheimer
      type (DAT) evidence more rapid forgetting than do patients with Huntington's
      disease (HD). The present study focused on whether such group differences
      translated into measures with adequate sensitivity and specificity at different
      stages of these disorders. It was found that measures of forgetting (i.e.,
      savings scores) based upon the Logical Memory and Visual Reproduction tests of
      the Wechsler Memory Scale--Revised had satisfactory to excellent sensitivity and
      specificity in differentiating DAT and HD patients from healthy control subjects.
      Savings scores also had good sensitivity and specificity in differentiating DAT
      from HD in the early stages of the diseases. However, unsatisfactory specificity
      may limit the utility of savings scores in differentiating among patients with
      moderate DAT and HD.

PMID- 8276936
TI  - Mirror reading in Alzheimer's disease: normal skill learning and acquisition of
      item-specific information.
AB  - Alzheimer's disease (AD) is characterized by severe explicit memory deficits and
      sparing of procedural learning. Most studies of skill learning in AD have been
      restricted to motor skills. This experiment was aimed at extending these studies
      to the domain of perceptual-verbal skills. Thirteen AD patients and 9 normal
      elderly controls were administered several explicit memory tests and a mirror
      reading paradigm with both unique and repeated word triads. In this last task, AD
      patients showed normal learning for unique word triads, that is, normal
      acquisition of the skill. Moreover, they benefitted from repeated triads to the
      same extent as did normal controls, although they were impaired in discriminating
      these repeated words from distractors at later recognition. These data
      demonstrate that patients with AD: (a) are able to learn and retain a perceptual
      verbal skill at a normal rate; (b) can learn item-specific information (repeated
      triads) at a normal rate, even though their explicit memory is severely impaired.
      It is hypothesized that learning of item-specific information relies on
      repetition priming effects rather than on explicit memory processes.

PMID- 8276937
TI  - Prospective memory impairment as an early indicator of dementia.
AB  - Theoretical accounts of the cognitive processes involved in prospective memory
      imply that performance on such tasks will be more vulnerable than retrospective
      memory tests to the early stages of dementia. This hypothesis is examined in
      elderly subjects from a general population sample which includes demented
      subjects. We report the findings on three tests of prospective memory from the
      Rivermead Behavioural Memory Test (Wilson et al., 1985) and compare it with
      measures of retrospective memory for recently acquired information. In contrast
      to retrospective memory where subjects with minimal dementia perform at a level
      intermediate between normals and more demented subjects, the subjects with
      minimal dementia perform as poorly as more demented subjects on the prospective
      memory tests. These findings provide evidence that prospective memory tasks are
      particularly sensitive to the early stages of dementia. Covariance analysis and
      the pattern of intercorrelations found between prospective and retrospective
      memory lead to alternative hypotheses about the cognitive processes involved in
      prospective memory and the way in which they break down.

PMID- 8276938
TI  - Memory, mood and measurement in hypothyroidism.
AB  - A 63-year-old female exhibited primary hypothyroidism, both upon clinical
      examination and laboratory tests. A full neuropsychological exam and repeated,
      multiple measures of affect, memory, concentration, and problem solving were used
      to establish baselines prior to treatment and to assess change during the first 7
      months of thyroid hormone replacement therapy. Additionally, thyroid hormone and
      metabolites T3, T4, TSH, and T3 (resin uptake) were regularly assessed. Results
      indicated that establishing stable baselines before treatment, long-term repeated
      assessments during treatment, and the use of control subjects are crucial to
      understanding the neuropsychological changes associated with hypothyroidism.
      Certain measures of depression, anxiety, attention, and concentration changed
      from severely impaired to normal levels following an explanation of the diagnosis
      but before actual treatment. Baseline memory functions were impaired before
      treatment and remained impaired relative to normals during replacement therapy in
      spite of improvement with repeated testing. However, replacement therapy may have
      arrested the progression of memory deterioration as no further decline was
      evident at a 7-month follow-up. Our data suggest that the memory changes
      associated with primary hypothyroidism may not be reversed by thyroid hormone
      replacement therapy.

PMID- 8276939
TI  - The role of cholinergic systems in visuospatial processing and memory.
AB  - Few studies have specifically addressed the cholinergic role in visuospatial
      memory. In the present study, we employed a randomized double-blind repeated
      measures design to investigate the effects of scopolamine on Judgement of Line
      Orientation (JLO) and two distinct visuospatial memory tasks. Complex Figures
      (CF) is a test of drawn reproduction similar to the Rey complex figure. The
      Spatial Array Memory Test (SAMT) is a two-dimensional free-recall visuospatial
      test which minimizes constructive skills and allows sensitive measurement of
      placement errors. Scopolamine impaired performance on JLO and CF. However, no
      effects of scopolamine on SAMT were apparent even though the SAMT is sensitive to
      aging and right temporal-lobe lesions. Selective effects of scopolamine on
      focused versus distributed attention may account for these differential results.

PMID- 8276940
TI  - Postpubertal disease status in diabetes and factor structure anomaly on the WISC
      R.
AB  - Diabetic children have been found to display an anomalous factor structure on the
      Wechsler Intelligence Scale for Children-Revised (WISC-R) (Holmes, Cornwell,
      Dunlap, Chen, & Lee, 1992). The present study sought to extend this finding with
      a larger cross-regional sample of children to determine which, if any,
      demographic or disease factor(s) might be related to the anomalous structure.
      Results revealed that groups of older (> = 12 years) children and those with late
      disease onset (> = 5 years) exhibited an anomalous four-factor structure in which
      the traditional Perceptual Organization factor (II) split into two factors:
      Picture Completion and Picture Arrangement formed a visual discrimination factor;
      and Block Design and Object Assembly created a spatial conceptual factor. It is
      postulated that diabetic performance on this visual discrimination factor may
      reflect mild visual neuropathies, often associated with adolescence and
      postpubertal disease status.

PMID- 8276941
TI  - Cellular aspects of corpus luteum function in the primate.
AB  - The primate corpus luteum produces progesterone for a period of 14-16 days, at
      which time, in non-fertile cycles, steroidogenesis ceases and the tissue
      regresses. Studies completed in this laboratory have established that while
      luteinizing hormone (LH) is necessary to maintain luteal steroidogenesis, changes
      in LH secretion are not causal to luteolysis. The studies presented here
      demonstrate that luteal cell synthetic capacity, as reflected in steady-state
      levels of messenger ribonucleic acid (mRNA) encoding steroidogenic enzymes, is
      maximal shortly after ovulation and steadily declines thereafter, independently
      of progesterone and LH secretion. In addition, the loss of luteal mRNA expression
      for steroidogenic enzymes following LH withdrawal occurs 24 h after the decline
      in progesterone levels. Finally, the detection of mRNA encoding vascular
      endothelial growth factor within the corpus luteum throughout the luteal phase in
      the subhuman primate may provide the first identification of a potential
      secreted, non-steroidal factor responsible for the vast degree of angiogenesis
      that occurs within the corpus luteum.

PMID- 8276942
TI  - Gonadotrophic and local control of the developing corpus luteum in rhesus
      monkeys.
AB  - The actions of the mid-cycle gonadotrophin surge to convert the pre-ovulatory
      follicle into the corpus luteum are not well understood in primate species. In
      experiments titrating the surge duration required in macaque monkeys during
      artificial in-vitro fertilization (IVF)-related cycles, short (< or = 14 h) LH
      surges similar to those in rodents and domestic animals failed to initiate peri
      ovulatory events. Attenuated (24 h) surges, one-half the duration of spontaneous
      surges in primates, reinitiated oocyte meiosis and initial luteinization of
      granulosa cells. However, only surges of > or = 48 h sustained luteal development
      and function to produce luteal phases of approximately 13 days. Three approaches
      immunocytochemistry of steroid receptors, binding of radiolabelled steroid, and
      reverse transcription-polymerase chain reaction of mRNA-indicate that
      progesterone receptor (PR), but not oestrogen receptor, is expressed in the
      macaque corpus luteum. Studies on cells collected before and after the
      gonadotrophin surge identified a novel action of LH to induce PR expression in
      luteinizing granulosa cells. Thus, the LH surge requirements vary between non
      primate and primate species, as well as between peri-ovulatory events, and the LH
      surge may promote cellular recognition of paracrine and autocrine factors (e.g.
      progesterone) that become predominant in the developing corpus luteum.

PMID- 8276943
TI  - The ovarian modulation of gonadotrophin releasing hormone-induced luteinizing
      hormone secretion in women.
AB  - Ovine pituitary cell culture and perfusion bioassays were used to investigate
      gonadotrophin surge-attenuating factor (GnSAF) bioactivity in vitro. GnSAF is
      present in steroid-free human follicular fluid (HFF) from superovulated women and
      specifically attenuates gonadotrophin releasing hormone (GnRH)-induced
      luteinizing hormone (LH) secretion. HFF produced dose-dependent suppression of
      GnRH-induced LH and basal FSH secretion, the former reflecting GnSAF bioactivity,
      the latter inhibin bioactivity. Heparin-Sepharose chromatography of HFF removed
      inhibin bioactivity, but not GnSAF bioactivity, indicating that these are
      distinct entities. Ultrafiltration of HFF suggests that GnSAF has a bioactive
      form of 10-30 kDa. Ovine pituitary perfusion demonstrated that GnSAF bioactivity
      in HFF is matched in the serum of superovulated and pregnant women. In addition,
      HFF and serum suppress both the initial and reserve pools of GnRH-induced LH
      secretion and greatly reduce the self-priming effect of GnRH in ovine pituitary
      tissue perfusion. In-vitro and in-vivo GnSAF bioactivity is consistent with a
      role for GnSAF in the gonadal feedback regulation of pituitary response to GnRH.

PMID- 8276944
TI  - The identification of gonadotrophin surge inhibiting factor and its role in the
      regulation of pituitary gonadotrophin secretion.
AB  - Evidence from several laboratories suggests that the ovaries of rats, pigs,
      monkeys and women produce a non-steroidal factor which inhibits or attenuates the
      mid-cycle gonadotrophin surge. This substance is present in follicular fluid and
      we have called it gonadotrophin surge inhibiting factor (GnSIF). Utilizing a rat
      pituitary cell bioassay, we have monitored GnSIF activity during purification
      from porcine follicular fluid (PFF). Rat pituitary cells in short-term culture
      were incubated with GnSIF for 48 h, washed and then exposed to gonadotrophin
      releasing hormone (GnRH) plus GnSIF for 4 h. GnSIF activity was defined as
      suppression of GnRH-stimulated LH secretion over 4 h, and inhibin activity was
      expressed as suppression of basal follicle stimulating hormone (FSH) secretion
      over 48 h. Approximately 5 l of PFF was fractionated through heparin-Sepharose, Q
      Sepharose, Mono-S, hydroxylapatite, and gel permeation chromatography steps. This
      fractionation removes all detectable inhibin and follistatin immunoactivity and
      bioactivity. The purified GnSIF inhibits GnRH-stimulated LH secretion with little
      or no effect on basal FSH release. In summary, we have obtained a purified
      preparation of GnSIF which contains undetectable inhibin and follistatin. As
      such, GnSIF appears to be distinct from other known gonadal proteins regulating
      reproductive function, and may participate along with the inhibins, activins and
      follistatins in the gonadal regulation of pituitary gonadotrophin secretion.

PMID- 8276945
TI  - Hypersecretion of luteinizing hormone and the polycystic ovary syndrome.
AB  - Hypersecretion of luteinizing hormone (LH) is a significant cause of infertility
      and miscarriage in women with the polycystic ovary syndrome. Many theories have
      been suggested for the aetiology of pituitary oversecretion of LH. These include
      increased pulsatility of gonadotrophin releasing hormone (GnRH) hypothalamic
      dysfunction, altered pituitary sensitivity to GnRH, hyperinsulinaemic stimulation
      of the pituitary gland and perturbed ovarian-pituitary feedback of steroid
      hormones. None of these hypotheses fully explain the phenomenon of LH
      hypersecretion and there has been much debate in the literature on this subject.
      This paper reviews some of the important clinical studies that have examined the
      evolving story of hypersecretion of LH and presents in-vivo and in-vitro evidence
      that suggests that disordered ovarian-pituitary feedback is central to the
      problem, possibly through a perturbed secretion of nonsteroidal ovarian hormones.

PMID- 8276946
TI  - Evidence for a negative feedback role of inhibin in follicle stimulating hormone
      regulation in women.
AB  - The pituitary--ovarian axis describes a regulatory system in which pituitary
      gonadotrophins stimulate ovarian folliculogenesis and the production of both
      steroid and protein hormones, which in turn exercise feedback control on the
      pituitary and hypothalamus. The availability of a radioimmunoassay for serum
      inhibin has allowed exploration of inhibin's role in the regulation of follicle
      stimulating hormone (FSH). This gonadotrophin stimulates ovarian inhibin
      secretion within the physiological dose range, both after exogenous
      administration and during endogenous rises, as are seen during puberty and the
      mid-cycle FSH surge. No direct evidence of FSH suppression by inhibin
      administered to human subjects has been obtained. During periods of endogenously
      raised inhibin levels, however, FSH is suppressed, as seen during the luteal
      phase of the menstrual cycle (luteinizing hormone drives inhibin production at
      that time), during pregnancy and in patients with inhibin-secreting granulosa
      cell tumors of the ovary. In contrast, decreased inhibin levels in the presence
      of intact hypothalamo-pituitary function result in increased FSH concentrations-
      as in early childhood, during the luteal-follicular transition and during
      reproductive ageing. After the menopause inhibin levels are normally
      undetectable, with FSH being markedly elevated. These observations are compatible
      with a role for endogenous inhibin in the regulation of FSH, though the
      contribution of oestradiol is in most instances impossible to dissect out
      separately.

PMID- 8276947
TI  - Quantitative two-site enzyme-linked immunosorbent assays for inhibin A, activin A
      and activin B.
AB  - We have developed three specific enzyme-linked immunosorbent assay (ELISA)
      formats which quantitate inhibin A in conditioned media and serum. The assays are
      sensitive in a range 0.078-5.0 ng/ml and have been characterized in terms of
      cross-reactivity to inhibin related proteins. The CK:CK assay format recognizes
      inhibin A, inhibin B and inhibin-related molecules, while the 9A9:CK assay format
      recognizes inhibin A and inhibin A precursors, but not free alpha-subunit. The
      11B5:CK assay appears to recognize only mature 32 kDa inhibin A. Additionally, we
      have developed separate, specific ELISA formats which quantitate activin A and
      activin B. The assays have a range of 0.2-50 ng/ml and 0.4-50 ng/ml for activin A
      and recombinant activin B, respectively. These assays are presently being used to
      examine the concentration of inhibin A, activin A and activin B in clinical serum
      samples.

PMID- 8276948
TI  - Clinical and pathophysiological aspects of inhibin.
AB  - Inhibin is a peptide hormone normally produced by the ovary. We have previously
      reported that serum inhibin concentrations are elevated in patients with
      granulosa cell tumours of the ovary. The aim of this study was to measure serum
      inhibin in a prospective, consecutive series of 200 patients admitted for
      suspected ovarian cancer. The serum inhibin radioimmunoassay had a sensitivity of
      77 mu/l. The median effective dose was 640 mu/l, while within- and between-assay
      coefficients of variation in the region of maximal assay precision were 4.3% and
      4.3%, respectively. The average effective doses (10 and 90%) in 35 consecutive
      assays were 211 and 1908 mu/l, respectively. We designated a serum inhibin
      concentration of > or = 130 mu/l as pathological in castrate or functionally
      agonadal women. Serum inhibin concentrations were elevated in 12 of 13 post
      menopausal patients with mucinous cystadenocarcinoma of the ovary. By contrast,
      elevated serum inhibin values were found in only nine of 65 women with non
      mucinous epithelial ovarian cancers. All patients showed a fall in serum inhibin
      levels to below 130 mu/l by 1 week after surgery. In post-menopausal women (n =
      54) with proven ovarian cancer, serum inhibin concentrations correlated
      negatively with serum FSH and the clinical stage of their disease (P < 0.05). By
      contrast, serum inhibin correlated positively with serum oestradiol and
      progesterone (P < 0.001) but there was no correlation between serum inhibition
      and serum CA-125 values. We conclude that serum inhibin concentrations are
      typically elevated in patients proven to have mucinous cystadenocarcinoma of the
      ovary.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276949
TI  - Stress and the gonadal axis in the female rhesus monkey: interface between the
      immune and neuroendocrine systems.
AB  - This paper is a short review of results obtained in the ovariectomized rhesus
      monkey relating to the interactions between the immune and adrenal/gonadal axes.
      The results indicate causative relationships between the activation of the
      adrenal axis and the acute suppression of the gonadal axis.

PMID- 8276950
TI  - Opioid control of gonadotrophin secretion in humans.
AB  - Hypothalamus-pituitary-axis (HPA) is constantly under the modulatory effect of
      many substances, such as neurotransmitters, neuromodulators and steroid hormones.
      Recently, the involvement of endogenous opioid peptides (EOP) in the control of
      the neuroendocrine mechanism modulating gonadotrophin secretion has been
      supported by several authors. It has been demonstrated that acute morphine
      administration decreases luteinizing hormone (LH) plasma levels and this is due
      to an inhibitory modulation on gonadotrophin releasing hormone discharge from the
      hypothalamic neurons. EOP are usually increased by stressful situations. In
      stress-induced amenorrhoea, the presence of low LH plasma levels and an abnormal
      LH pulsatile secretion has been related to an increased opioid activity, thus
      supporting the integrative role of opioids between hormonal and neuronal
      afferences of brain.

PMID- 8276951
TI  - The control of the gonadotrophin releasing hormone pulse generator in relation to
      opioid and nutritional cues.
AB  - Human fertility is ultimately dependent upon the regular pulsatile release of
      gonadotrophin releasing hormone (GnRH) from hypothalamic neurons. The GnRH pulse
      generator is subject to modulation by a variety of substances, some of which
      reflect the individual's metabolic status. Endogenous opioids exert a tonic
      inhibitory effect on GnRH release; this opioid inhibition is dependent upon the
      gonadal steroid milieu, and may play a role in the initiation of the mid-cycle
      luteinizing hormone surge. Putative metabolic signals also influence the GnRH
      pulse generator, and after performing a cross-sectional hormonal and metabolic
      analysis of amenorrhoeic athletes, we propose that insulin-like growth factor
      binding protein 1 (IGFBP-1) is such a signal and may play a role in the
      initiation of puberty.

PMID- 8276952
TI  - Modulation of reproductive hormone secretion by nutritional intake: stress
      signals versus metabolic signals.
AB  - States of chronic undernutrition can cause a profound suppression of reproductive
      function. To begin to determine the time course and the nature of the mechanism
      by which undernutrition suppresses the activity of the reproductive axis we have
      examined the effects of brief periods of fasting on reproductive hormone
      secretion in men and male rhesus monkeys. In monkeys there is a significant
      suppression of pulsatile luteinizing hormone (LH) and testosterone secretion
      after a single day of fasting, that is apparent within the first 4 h after a meal
      is missed. The suppression of pulsatile LH secretion on a day of fasting does not
      appear to be caused by the psychological stress experienced when monkeys are
      deprived of their daily meal in that monkeys who are maintained in a
      metabolically fed state (by feeding a large excess of food on the day prior to
      fasting), but are deprived of a meal and displayed behavioural agitation
      associated with fasting, have no suppression of LH secretion. The suppression of
      LH secretion on a day of fasting cannot be reversed by naloxone infusion,
      indicating that increased secretion of opioid peptides is not the primary
      mechanism causing the decrease in the central drive to the reproductive axis
      during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276953
TI  - Opiate antagonist treatment of ovarian failure.
AB  - One-hundred-and-thirty-eight women suffering from hypothalamic or hyperandrogenic
      ovarian failure were treated with daily doses of 25-150 mg of the opiate
      antagonist naltrexone for 4-100 weeks. In patients with hypothalamic ovarian
      failure, treatment with naltrexone alone was followed by an increase of
      gonadotrophins and by normalization of the menstrual cycle in approximately 70%
      of patients. Eight of 10 patients who did not respond to naltrexone and had not
      previously ovulated in response to clomiphene administration exhibited ovulatory
      cycles when both compounds were administered. Twenty-four pregnancies were
      achieved in 22 women, corresponding to an overall pregnancy rate of 26%, with a
      cumulative pregnancy rate closely resembling that of a normal population. In
      contrast, in hyperandrogenic insulin-resistant patients, the pattern of
      gonadotrophin secretion did not seem to change dramatically during naltrexone
      treatment. However, the rise of insulin in plasma following an oral load of
      glucose (oGTT) was blunted considerably, resulting in normalization of previously
      elevated circulating insulin levels. Since the time course of plasma glucose
      after oGTT did not appear to be affected by treatment, this indicates an increase
      in insulin sensitivity (or a decrease in insulin resistance) during naltrexone
      therapy. Side-effects of naltrexone treatment were negligible in patients with
      hypothalamic ovarian failure. Hyperandrogenic patients, however, did experience
      more intense and prolonged side-effects, such as nausea and dizziness.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276954
TI  - Pulsatile gonadotrophin releasing hormone versus gonadotrophin treatment of
      hypothalamic hypogonadism in males.
AB  - In this study, pulsatile gonadotrophin releasing hormone (GnRH) therapy and
      gonadotrophin therapy were compared for male patients with idiopathic
      hypothalamic hypogonadism. Thirty-six patients, 19 with this condition, and 17
      with Kallmann's syndrome, were included in the study. Their mean age was 21.1 +/-
      3.0 years (+/- SD). They were divided into two groups of similar age, number and
      testicular volume. Pulsatile GnRH therapy was started with 4 micrograms GnRH s.c.
      every 2 h using a portable pump and gonadotrophin therapy with weekly i.m.
      injections of 3 x 2500 IU human chorionic gonadotrophin (HCG). After 8-12 weeks
      of HCG treatment, 150 IU human menopausal gonadotrophin (HMG) 2-4 times weekly
      were added and the dose of HCG reduced if necessary. Testosterone concentrations
      increased significantly more (P < 0.03) in the gonadotrophin group than in the
      GnRH group (22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/l). The rise in oestradiol
      levels was also significantly higher (P < 0.001) in the gonadotrophin group than
      in the GnRH group (150 +/- 70 versus 88 +/- 59 pmol/l). Five patients developed
      gynaecomastia during gonadotrophin therapy. An increased testicular volume (TV)
      occurred more rapidly (P < 0.001) and was significantly more pronounced (P <
      0.001) after GnRH therapy (delta TV = 8.1 +/- 2.0 ml) than with gonadotrophins
      (delta TV = 4.8 +/- 1.8 ml). Sperm counts were performed in 14 patients given
      GnRH and in 17 patients given gonadotrophins. Ten patients given GnRH had
      positive sperm counts, ranging from 1.5 to 14 x 10(6) spermatozoa/ml; eight of
      those given gonadotrophins also developed spermatogenesis (2-26 x
      10(6)/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276955
TI  - Control of pulsatile secretion of gonadotrophin releasing hormone from
      hypothalamic explants.
AB  - We have studied the secretion of gonadotrophin releasing hormone (GnRH) from
      hypothalamic explants of male rats at different ages in an attempt to delineate
      the neuroendocrine mechanism of the onset of puberty. In this paper, we review
      some of our recent studies and we provide evidence of a dual control played by
      receptors to neuroexcitatory amino acids. We showed previously that isolated
      explants of rat hypothalamus could secrete GnRH in a pulsatile manner. The onset
      of puberty was characterized by a 2-fold increase in frequency of GnRH secretory
      pulses. This reduction of the interval between GnRH pulses involved an inhibitory
      autofeedback effect of GnRH on the pulse generator which was shut off following a
      secretory episode. This period of refractoriness was longer before puberty than
      after the onset of puberty. Activation of receptors to neuroexcitatory amino
      acids (N-methyl-D-aspartate; NMDA-type) was involved in the mechanism of
      pulsatile GnRH secretion. Striking developmental changes in NMDA-receptor
      mediated GnRH secretion were demonstrated with a maximal activity around the time
      of the onset of puberty. Similar changes occurred in orchidectomized animals,
      indicating that this maturational process was gonad-independent. While evidence
      accumulated that NMDA receptors were involved in a stimulatory control of GnRH
      secretion, we found that NMDA receptors mediated an inhibitory effect on GnRH
      secretion. This inhibitory effect was very potent in the immature hypothalamus
      and it showed a marked reduction in potency before onset of puberty.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8276956
TI  - Pulsatile GnRH treatment in boys and girls with idiopathic hypogonadotrophic
      hypogonadism.
AB  - In order to induce pubertal development, low-dose, pulsatile gonadotrophin
      releasing hormone (GnRH) was administered i.v. in adolescent boys and girls with
      an isolated hypogonadotrophic hypogonadism. The first study included GnRH
      treatment in 21 male patients with the goal of initiating testicular growth and
      spermatogenesis; in the second study, GnRH was administered in three adolescent
      boys and two girls in an increasing pulse frequency as well as pulse dose in
      order to imitate the 'physiological' pubertal changes. In the first study
      gonadotrophin and testosterone levels increased in all patients, and testicular
      growth also occurred. When GnRH treatment was discontinued spermatogenesis was
      present in 14 out of the 17 patients examined, and was observed in another
      patient during subsequent human chorionic gonadotrophin (HCG) treatment.
      Ultimately, 15 out of the 19 patients developed spermatozoa. In the second study,
      small increases in luteinizing hormone (LH) and follicle stimulating hormone
      (FSH) were observed during a low-frequency GnRH schedule, followed by a further
      rise during the 'physiological' schedule with a 90-min pulse interval;
      testosterone and oestradiol also increased. An increased secretion of growth
      hormone occurred only in boys during GnRH treatment, after their testosterone
      levels had increased. In girls, none of the GnRH treatment schedules was
      associated with an increase in growth hormone. Pulsatile GnRH treatment is thus
      feasible as a method of inducing testicular growth and spermatogenesis. A GnRH
      treatment schedule with an increasing pulse frequency and pulse dose can imitate
      the 'physiological' pubertal changing pattern of gonadotrophins just as well as
      the use of sex steroid. However, with respect to growth hormone secretion, GnRH
      will induce an increase in boys only.

PMID- 8276957
TI  - Pulsatile administration of gonadotrophin releasing hormone and oral
      administration of naltrexone in hypothalamic amenorrhoea.
AB  - Between 1979 and 1990, 73 patients suffering from hypothalamic amenorrhoea were
      treated by pulsatile administration of gonadotrophin releasing hormone (GnRH) in
      359 treatment cycles. Seventy-two pregnancies were achieved. In 64 favourable
      patients in whom hypothalamic amenorrhoea constituted the only reason for
      infertility, a pregnancy rate of 29% per cycle could be obtained. Patients who
      conceived during pulsatile GnRH required an average of only 2.4 cycles per
      conception. Twelve out of 24 patients with hypothalamic amenorrhoea who exhibited
      an ovulatory response to pulsatile GnRH, ovulated during oral administration of
      naltrexone; such responsiveness to opioid antagonism was, however, restricted to
      the less serious grades. In conclusion, pulsatile administration of GnRH
      continues to be a highly effective mode of treatment of infertility due to
      hypothalamic amenorrhoea of various aetiologies. A subgroup of these patients may
      be successfully treated by the oral administration of naltrexone.

PMID- 8276958
TI  - Multiple follicular growth under pulsatile gonadotrophin releasing hormone
      stimulation.
AB  - Pulsatile gonadotrophin releasing hormone (GnRH) treatment in patients with
      secondary hypothalamic amenorrhoea results in higher multiple pregnancy rates
      than expected. This multiple pregnancy rate is significantly higher when
      conception occurs during the first treatment cycle and when higher pulse doses
      are used. This is probably due to higher follicle stimulating hormone (FSH)
      levels, leading to multiple follicular growth. The endocrinology of pulsatile
      i.v. GnRH treatment cycles in patients with hypothalamic amenorrhoea as well as
      in patients with normal cycles revealed higher FSH levels during the first days
      of treatment compared with unstimulated control cycles. It was possible to induce
      multiple follicular growth in normally cycling women with pulsatile GnRH. To
      prevent multiple pregnancies in patients with hypothalamic amenorrhoea, a low
      pulse dose should be used, especially during the first treatment cycles.

PMID- 8276959
TI  - Pulsatile intravenous gonadotrophin releasing hormone for ovulation induction:
      determinants of follicular and luteal phase responses.
AB  - When anovulation results from a deficiency of gonadotrophin-releasing hormone
      (GrRH), substitution therapy with pulsatile peripheral i.v. GnRH is almost always
      successful. A review of published papers leads to the following conclusions for
      achieving the best results: (i) the i.v. route is superior to the s.c. route;
      (ii) the pulse interval should lie between 90 and 60 min, and may be shortened,
      but not lengthened, as follicular response takes place; (iii) the pulse dose for
      i.v. administration should be approximately 75 ng/kg (in practice, 2.5
      micrograms/pulse for women weighing < 50 kg and 5.0 micrograms/pulse for women
      weighing > 50 kg is satisfactory). The more profound the degree of hypothalamic
      and pituitary suppression when GnRH is started, the longer the preliminary rise
      in FSH will last and the longer will be the duration of the follicular phase. The
      greater the tendency towards exaggerated LH release (indicating polycystic ovary
      syndrome), the less likely it is that satisfactory follicular development will
      follow. The luteal phase depends on (i) the adequacy of follicular development,
      (ii) the adequacy of the ovulatory stimulus, and (iii) continued trophic stimulus
      from LH or from administered human chorionic gonadotrophin. Ovulation rates with
      pulsatile GnRH in hypothalamic chronic anovulation should exceed 95% and appear
      limited only by technical failures.

PMID- 8276960
TI  - Pulsatile gonadotrophin releasing hormone stimulation after medium-term pituitary
      suppression in polycystic ovary syndrome.
AB  - Ovulation induction in the polycystic ovary syndrome with pulsatile gonadotrophin
      releasing hormone (GnRH) in the recovery phase after treatment with a GnRH
      agonist (GnRHa) during 6-8 weeks has been reported to improve ovulation and
      pregnancy rates and to normalize follicular phase luteinizing hormone (LH)
      levels. We studied the results of stimulation with pulsatile GnRH after a shorter
      'medium-term' period of 3 weeks of treatment with a GnRHa by comparing a cycle
      without GnRHa pre-treatment with a cycle with GnRHa (post-GnRHa) pre-treatment in
      12 patients. We could prove no significant clinical improvement in post-GnRHa
      cycles. Ovulation rates were similar. However, in the post-GnRHa cycles, two
      ongoing pregnancies were observed versus one spontaneous abortion in the cycles
      without GnRHa pre-treatment. This observation might be explained by the fact that
      follicular phase LH levels in post-GnRHa cycles were significantly decreased.

PMID- 8276961
TI  - Studies on the neuronal systems involved in the oestrogen-negative feedback
      effect on gonadotrophin releasing hormone neurons in the ewe.
AB  - Oestrogen can act on the brain to exert negative and positive feedback effects on
      the secretion of gonadotrophin releasing hormone (GnRH), but this cannot be
      effected through the GnRH cells themselves because they have no oestrogen
      receptors. We have used intraventricular injection of agonists and antagonists of
      various transmitters to determine which systems are involved in the control of
      GnRH by steroid hormones. We have also developed a model for the injection of
      drugs directly into the medial pre-optic area of the sheep brain to study the
      action on the GnRH cell bodies. Opioid systems seem to be involved in the
      mediation of the feedback effects of progesterone, but not oestrogen.
      Noradrenaline appears to be involved in the negative feedback regulation of GnRH
      secretion during the anoestrous period. Thus, under the strong negative influence
      of oestrogen at this time GnRH/luteinizing hormone (LH) secretion is reduced but
      can be restored by the preoptic micro-injection of noradrenaline. Gamma-amino
      butyric acid (GABA) agonists and antagonists inhibit LH secretion when injected
      into the medial pre-optic region of the hypothalamus of ovariectomized ewes with
      or without oestrogen treatment. We have no evidence that GABA is involved in the
      negative feedback regulation of GnRH, since neither agonists nor antagonists will
      reverse the effects of steroid feedback. There appears to be a shift in the GABA
      receptor subtype function with season; in the breeding season only GABAA ligands
      are effective, whereas during the non-breeding season both GABAA and GABAB type
      ligands will affect LH secretion. This suggests that the seasonal shift in
      responsiveness to the negative feedback effects of oestrogen involves a shift in
      the function of GABA receptor subtypes.

PMID- 8276962
TI  - Pulsatile administration of gonadotrophin releasing hormone as a diagnostic tool
      to distinguish hypothalamic from pituitary hypogonadism following neurosurgery.
AB  - Nine patients suffering from severe amenorrhoea following neurosurgical or
      radiotherapy for pituitary tumour or craniopharyngeoma were treated with
      pulsatile gonadotrophin releasing hormone (GnRH) administration. Seven patients
      did exhibit ovulatory cycles when GnRH was administered i.v. at a dose of 20
      micrograms/pulse, but not at lower doses or when GnRH was administered s.c.
      Pulsatile GnRH administration may be used to assess the functional integrity of
      pituitary gonadotrophs and to distinguish pituitary from hypothalamic site of
      lesion resulting in hypogonadotrophic hypogonadism. It may also be used
      successfully for treatment of infertility in such patients.

PMID- 8276963
TI  - Management of pituitary gonadal function via gonadotrophin releasing hormone
      (GnRH) antagonists, including ovulation induction by co-administration of either
      gonadotrophins or pulsatile GnRH.
AB  - GnRH agonists are now familiar clinical agents and are often the drugs of choice
      for suppression of the pituitary gonadal axis as part of various clinical
      indications. GnRH antagonists, which are likely to become clinically available
      soon, offer several advantages over the currently available GnRH agonists for
      many applications including ovulation induction. Here, we review the results from
      a series of pre-clinical studies designed to evaluate the potential clinical
      utility of this new class of compounds for ovulation induction protocols.

PMID- 8276964
TI  - Molecular mechanisms of gonadotrophin releasing hormone-stimulated gonadotrophin
      secretion.
AB  - Hypothalamic gonadotrophin releasing hormone (GnRH) exerts its effect on
      gonadotrophin synthesis and release via plasma membrane-bound receptors. The
      exocytosis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is
      activated by the binding of GnRH or its agonists to receptors in pituitary cells,
      which initiates a number of post-receptor events within the gonadotroph cell.
      Various potential second messengers have been claimed to mediate the stimulatory
      action of GnRH including calcium, inositol phosphates, protein kinase C,
      arachidonic acid metabolites and cyclic nucleotides. It appears that more than
      one of these pathways is required to fully mimic the GnRH effect.

PMID- 8276965
TI  - Regulation of gonadotrophin subunit gene expression.
AB  - Physiological regulation of gonadotrophin subunit gene expression was
      investigated in vivo by cDNA-mRNA hybridization from individual pituitary glands
      from rats and mice. Common alpha, LH-beta, FSH-beta mRNA increased in a time
      dependent manner after orchidectomy and ovariectomy of rats, the increases being
      prevented by testosterone and oestradiol, respectively, in male and female rats.
      Increases in all three subunit mRNAs after gonadectomy were prevented by a GnRH
      antagonist and antiserum, and were reduced by the same treatments in intact rats,
      indicating their dependence on endogenous GnRH. Further evidence for GnRH
      influences on gonadotrophin gene activation comes from pulsatile GnRH treatment
      of GnRH deficient hypogonadotrophic hypogonadal mice in which this induced alpha
      and LH-beta mRNA to supranormal and normal values, respectively. Pituitary
      desensitization with GnRH agonist infusion markedly suppressed LH-beta and FSH
      beta mRNA levels and pituitary LH accumulation, but paradoxically increased alpha
      subunit mRNA to castrate levels in intact rats and failed to suppress alpha mRNA
      in castrated rats. These results indicate the divergent regulation of alpha and
      specific LH-beta/FSH-beta mRNA in vivo and that the latter are closely related to
      LH/FSH synthesis and secretion and physiological GnRH stimulation of the
      pituitary. In-vitro studies suggest that physiological GnRH induces transcription
      from beta subunit genes and also stabilizes their mRNAs, possibly by altering
      mRNA length. Preliminary studies to investigate regulatory elements in the 5'
      region of the LH-beta gene suggest the presence of an atypical cAMP responsive
      element since an LH-beta-CAT construct can be induced by 3-fold in a transient
      heterologous cell expression system.

PMID- 8276966
TI  - Electrophysiological approaches to gonadotrophin releasing hormone pulse
      generator activity in the rhesus monkey.
AB  - Precipitous increases in multi-unit electrical activity (MUA volleys) can be
      recorded from the mediobasal hypothalamus of the rhesus monkey that are
      invariably synchronous with the initiation of luteinizing hormone (LH) pulses and
      thus serve as markers of gonadotrophin releasing hormone (GnRH) pulse generator
      activity. Continuous radiotelemetric monitoring of this activity throughout the
      menstrual cycle confirmed a lower pulse generator frequency during the luteal
      phase than in the follicular phase. Unexpectedly, however, just before the
      initiation of the LH surge an abrupt reduction in frequency was observed,
      followed, on occasion, by a total arrest of GnRH pulse generator activity for a
      day or two. This monitoring technique also revealed a reduction of pulse
      generator frequency at night. This appeared to be an acute phenomenon observable
      in the first MUA volleys after the lights are turned off, as is the increase in
      frequency when the lights are turned on in the morning suggesting a direct action
      of light, a conclusion that was verified using lighting periods other than the
      customary ones. This action of light, however, is superimposed upon a diurnal
      rhythm, as shown by a reduction in pulse generator frequency during the
      subjective night when the monkeys are kept in constant light or darkness. The
      duration of the MUA volley in the intact monkey is 1-3 min, compared with some 20
      min in the ovariectomized female. While oestradiol reduces the volley duration in
      the ovariectomized female to that of intact monkeys within 6 h, it takes some 6
      weeks following ovariectomy for the duration characteristic of castrates to be re
      established.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276967
TI  - The follicle stimulating hormone-inhibin feedback loop in male primates.
AB  - This paper reviews our current knowledge of the role of testicular inhibin in the
      regulation of follicle stimulating hormone (FSH) secretion in the rhesus monkey.
      Species differences between monkey and rat are described, and evidence for and
      against the hypothesis that control of FSH secretion in the human male is similar
      to that for the monkey is presented.

PMID- 8276968
TI  - Gonadotrophin-releasing hormone analogue-induced manipulation of testicular
      function in the monkey.
AB  - In this paper the properties of a novel group of compounds, gonadotrophin
      releasing hormone antagonists, are used to study the regulation of testicular
      function. These studies provide the basis for new developments in male
      contraception.

PMID- 8276969
TI  - Characterization and regulation of pre-ovulatory secretion of gonadotrophin
      releasing hormone.
AB  - Using an elegant method for sampling of pituitary portal blood the secretory
      characteristics of gonadotrophin-releasing hormone (GnRH) during the oestradiol
      induced surge are studied. It is demonstrated that the neuroendocrine signal for
      ovulation in the ewe is a surge of GnRH released into the portal blood.

PMID- 8276970
TI  - The role of changing pulse frequency in the regulation of ovulation.
AB  - Ovulatory cycles in women result from sequential stimulation of ovarian
      follicular development by pituitary follicle stimulating hormone (FSH) and
      luteinizing hormone (LH). In the follicular phase the initial FSH stimulus
      declines and LH secretion increases toward the mid-cycle ovulatory surge. During
      the luteal phase gonadotrophin secretion is reduced. This reflects the effects of
      ovarian steroids inhibiting the frequency of gonadotrophin releasing hormone
      (GnRH) secretion by the hypothalamus, and the direct effects of oestradiol and
      inhibin to reduce gonadotroph (FSH) secretion. The frequency of GnRH stimulation
      of the gonadotroph is a selective regulator of gonadotrophin synthesis, with slow
      frequency stimuli favouring FSH and faster frequency stimuli favouring LH
      secretion. Current research has only revealed a single gonadotrophin releasing
      hormone. Thus, the ability to change the pattern (particularly frequency) of GnRH
      stimulation of the gonadotroph is proposed as an important regulator of
      differential FSH and LH synthesis, and hence of ovulatory cycles. In some
      disorders of ovulation the ability to regulate GnRH pulse frequency appears to
      have been lost. Slow frequency GnRH pulses are consistently seen in women with
      hypothalamic amenorrhoea and hyperprolactinaemia. The reduced GnRH secretion
      appears to reflect increased hypothalamic opiate tone and can be rapidly reversed
      with an opiate receptor blocker. Other disorders associated with anovulation show
      rapid frequency GnRH secretion, and polycystic ovarian syndrome (PCO) is commonly
      associated with fast-frequency, high-amplitude LH (GnRH) pulses. Such a GnRH
      stimulus would favour LH and androgen production and the failure of ovarian
      follicular maturation in PCO may reflect inappropriate sequential FSH
      secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276971
TI  - Role of gonadotrophin releasing hormone secretory dynamics in the control of the
      human menstrual cycle.
AB  - The pattern of episodic gonadotrophin releasing hormone (GnRH)-driven luteinizing
      hormone (LH) secretion changes dynamically across the human menstrual cycle.
      Adherence to a specific regimen of pulse amplitude and frequency is critical for
      normal ovulation, menstrual cyclicity and reproductive function. Derangements of
      episodic LH secretion are associated with anovulation. We have shown that in the
      human slowing of GnRH-induced LH pulses results in lower ovulatory rates and
      dysfunctions of the mid-cycle LH surge. This information is relevant for the
      understanding of the endocrine dynamics of the menstrual cycle both in normal and
      anovulatory subjects.

PMID- 8276972
TI  - Gonadotrophin releasing hormone pulse generator activity before and during sexual
      maturation in girls: new insights.
AB  - The activity of the gonadotrophin releasing hormone (GnRH) pulse generator during
      pubertal transition was investigated in 40 healthy girls 7-18 years of age. Ten
      were pre-pubertal, seven were in early puberty, and 23 were post-menarcheal.
      Serum concentrations of luteinizing hormone (LH) and follicle stimulating hormone
      (FSH) were measured with immunofluorimetric assays, which have a sensitivity
      approximately 100-fold that of radioimmunoassay, in samples taken at 10-min
      intervals for 24 h during basal conditions, during Nal-Glu antagonist
      suppression, and in response to GnRH stimulation (10 micrograms). Serum levels of
      androstenedione, testosterone and oestradiol were measured by radioimmunoassay.
      Our data show that the GnRH pulse generator is functionally active in prepubertal
      girls with selective expression of LH and FSH pulses after the onset of sleep.
      The onset of puberty is associated with a greater increase in LH pulse amplitude
      than frequency. These overall changes are punctuated by a switch of wake/sleep
      activities of GnRH pulse generator with a progressive increase in day-time
      pulsatility and a gradual reduction of sleep-entrained amplification. While LH
      pulsatility appears to be highly GnRH dependent at all ages, a remarkable
      decrease in the predominance of GnRH regulation of FSH pulsatility occurs in
      conjunction with ovarian activation.

PMID- 8276973
TI  - Laterality of the gonadotrophin releasing hormone pulse generator in the rat:
      interaction of neurons located in both preoptic areas as a basic feature.
AB  - Though the pivotal importance of pulsatile gonadotrophin releasing hormone (GnRH)
      release from the hypothalamus for sufficient luteinizing hormone (LH) secretion
      is well recognized, the mechanisms causing GnRH pulses are still largely unknown.
      In the rat, the GnRH neurons are concentrated in the preoptic area, which is a
      bilateral structure of the anterior hypothalamus. This distribution into two
      distinct brain areas raises the question of whether the GnRH neurons in both
      preoptic areas are simultaneously or alternatively active and whether an
      interaction between both areas is required to generate GnRH pulses. We addressed
      these questions by unilateral manipulations of the activity of GnRH neurons using
      either electrical lesion or local infusion of gamma-aminobutyric acid (GABA), a
      neurotransmitter known to inhibit LH release via a hypothalamic action. Acute
      lesion of one preoptic area caused complete cessation of pulsatile LH release
      which was restored after 48 h. An acute inhibition of LH release was also
      observed after unilateral preoptic application of GABA. It is concluded that an
      interaction of both preoptic areas is mandatory for GnRH pulse generation.
      However, we suggest that the pacemaker function is not intrinsic to GnRH nor GABA
      neurons but the cross-talk between these neurons within and between both preoptic
      areas results in episodic GnRH release.

PMID- 8276974
TI  - Luteinizing hormone (LH) pulsatility during the oestradiol- and
      oestradiol/progesterone-induced LH surge in the human female.
AB  - Positive feedback reactions were induced in five female volunteers with regular
      menstrual cycles on the pituitary secretion of luteinizing hormone (LH) during
      the follicular phase of the cycle by the i.m. administration of oestradiol
      benzoate ('oestradiol study'), or by oestradiol benzoate followed by progesterone
      ('oestradiol/progesterone study'). Prior to the administration of the steroids
      (basal profiles) and during the LH surges following the administration of the
      steroids (stimulation profiles), blood was drawn at 10-min intervals and the LH
      pulsatility assessed. The LH pulses occurred at hourly intervals in basal and
      stimulation profiles, which concurs with data obtained during the normal
      proliferative phase and the spontaneous mid-cycle surge of the cycle in both the
      human and the rhesus monkey. Our findings are, however, in sharp contrast with
      those obtained in the rhesus monkey by the determination of hypothalamic multi
      unit activity.

PMID- 8276975
TI  - Ultradian and circadian patterns in luteinizing hormone secretion during
      reproductive life in women.
AB  - Based on the findings of close links between intermittent hypothalamic releasing
      hormone stimulation and hypophyseal gonadotrophin response, an assessment of the
      pulsatility of serum gonadotrophins may represent a feasible way to indirectly
      evaluate central regulatory processes in humans. Since ovarian steroid feedback
      is virtually absent in hypogonadal women, their luteinizing hormone (LH)
      pulsatility may represent the unrestrained LH pulse rhythm at its maximal rate.
      Relative changes in the LH pulse characteristics during the menstrual cycle could
      then be referred to this basic pulsatility. Hence, LH pulse frequencies increase
      during cycle periods of high sex steroid exposure, but this increase is limited
      to the LH periodicities found in hypogonadal women. Furthermore, LH pulse
      amplitudes are successively enhanced from the follicular to the luteal phase of
      the cycle yet they never exceed those found in hypogonadal subjects. In addition,
      circadian excursions subserve pulsatile LH secretion during all periods of the
      menstrual cycle, although the character of these circadian rhythmicities differs
      from that observed in the LH secretory profiles of hypogonadal women. Thus,
      albeit profoundly modulated by ovarian sex steroid feedback during the menstrual
      cycle, LH pulsatility and its circadian variations in women during the menstrual
      cycle is confined to the ultradian and circadian LH secretory patterns of the
      hypogonadal state.

PMID- 8276976
TI  - Steroidal regulation of biologically active luteinizing hormone secretion in men
      and women.
AB  - The biological activity of circulating luteinizing hormone (LH) molecules can be
      assessed with high sensitivity, specificity, and precision by the in-vitro rat
      interstitial (Leydig)-cell testosterone (RICT) bioassay. Compared to
      immunoreactive estimates of the LH content of plasma, the living Leydig-cell
      bioassay integrates the functional in-vitro potency of all circulating LH
      isoforms, while simultaneously reflecting the effects of otherwise potentially
      confounding in-vivo antagonists of LH action on steroidogenesis. Here, we review
      the pathophysiological regulation by steroid hormones of bioactive LH secretion
      and clearance in men and women. Our investigations and those in the available
      literature indicate that: (i) exogenous (non-aromatizable) 5-alpha
      dihydrotestosterone infusion suppresses LH bioactivity, whereas blockade of the
      endogenous androgen receptor with flutamide increases secretion of biopotent LH
      in men; (ii) endogenous androgen excess due to a masculinizing testosterone
      secreting adrenal tumour in a post-menopausal woman reversibly suppressed plasma
      LH bioactivity markedly; (iii) exogenous oestradiol infusion will reduce whereas
      the antioestrogen, tamoxifen-HCl, can increase bioactive LH secretion in young
      men; (iv) the effect of anti-oestrogen is blunted in healthy older men; (v)
      endogenous hyperoestrogenism due to an adrenal oestrogen-secreting tumour in a
      middle-aged man with gynaecomastia profoundly but reversibly inhibited bioactive
      LH secretion; (vi) in post-menopausal women, exogenous oestrogen administration,
      whether oral (diethylstilbestrol), percutaneous (oestradiol), or intravaginal
      (oestradiol-impregnated silastic ring), exerts a temporally biphasic effect on
      basal bioactive LH secretion, i.e. acute suppression (within 24 h), subacute
      escape (at 5-10 days), and longer-term inhibition (30 days); (vii) during the
      normal menstrual cycle, bioactive LH secretion is pulsatile and both frequency
      and amplitude regulated; and (viii) oestrogen exposure can enhance gonadotrophin
      releasing hormone (GnRH)'s stimulatory action on biologically active LH
      secretion, resulting in so-called GnRH self-priming. Oestrogen's facilitative
      effects are achieved by a novel mechanism, in which oestrogen augments LH
      secretory burst mass and duration. Moreover, GnRH dose-LH secretory response
      studies show that oestrogen promotes an increase in GnRH efficacy (maximal
      effects) but not GnRH sensitivity (potency or half-maximally effective doses of
      GnRH). We conclude that steroid hormones are primary regulators of
      physiologically pulsatile bioactive LH secretion in healthy men and women.
      Moreover, steroids exert potent pathological effects on biologically active LH
      release in conditions of selective hyperandrogenism or hyperoestrogenism due to
      steroid-secreting adrenal or gonadal tumours.

PMID- 8276977
TI  - The control of gonadotrophin secretion by ovarian steroids.
AB  - Ovarian steroids exert feedback effects at the level of both the hypothalamus and
      anterior pituitary to regulate the secretion of gonadotrophins. Oestradiol
      decreases the activity of mRNA encoding the alpha and beta subunits of
      gonadotrophins. In the late follicular phase, oestradiol exerts a positive
      feedback control over pituitary luteinizing hormone (LH) release and a negative
      control over follicle stimulating hormone (FSH). Oestradiol also induces a pre
      ovulatory increase of gonadotrophin releasing hormone (GnRH) secretion which is
      continuous rather than episodic. Such a GnRH rise may not be required to produce
      the LH surge. Progesterone exerts its major effect at the hypothalamic level and
      decreases GnRH pulse frequency by inducing the release of beta-endorphin.
      However, the hypothalamus is not the exclusive target of progesterone action, for
      its facilitatory action on gonadotrophin release may be at the level of the
      pituitary gland. This positive feedback effect was studied in women with
      hypothalamic gonadotrophin deficiency treated with pulsatile GnRH. In
      physiological doses, progesterone had a stimulatory effect on LH secretion at the
      pituitary level. Finally, regarding the effect of androgens upon gonadotrophin
      secretion, the administration of a non-steroidal pure anti-androgen (Flutamide)
      for 12 months in 10 normally cycling women did not change significantly the mean
      levels, frequency, or amplitude of LH pulses or the LH and FSH responsiveness to
      GnRH. Androgens (apart from their aromatization to oestrogens) do not directly
      play a physiological role in gonadotrophin regulation in normal women.

PMID- 8276978
TI  - Progression of periodontal tissue destruction at splinted/non-splinted teeth. An
      experimental study in the dog.
AB  - The aim of the present investigation was to study whether splinting, i.e.,
      immobilisation of teeth, may interfere with the rate of periodontal tissue
      destruction that can be accomplished by ligature placement and plaque
      accumulation, 5, 1-year-old, beagle dogs were included in the experiment. The
      mandibular 2nd and 3rd premolars and the 1st molar on both sides of the mandible
      were extracted. 2 titanium implants were installed in the sites of 3P and 1M,
      i.e., in the right quadrant of the mandible. 3 months later, abutment connection
      was performed and a fixed, gold splint, connecting the tooth and the implants,
      was inserted. The non-resilient splint was cemented in place on Day 0 and 4P was
      hereby immobilized. In each dog, the contralateral fourth premolar (P4) served as
      the non-splinted control tooth. Experimental periodontal tissue breakdown was
      initiated by placing cotton floss ligatures around the neck of 4P and P4 and by
      allowing the animals to accumulate plaque and calculus. Once every month, new
      ligatures were placed at the level of the receding gingival margin. The
      experiment was terminated on Day 180. Radiographs of 4P and P4 were obtained and
      biopsies sampled. The results of the measurements, made in the radiographs and
      the histological sections, disclosed that the splinting of the experimental
      teeth, failed to prevent or retard apical downgrowth of plaque and associated
      attachment loss. It was concluded that increased tooth mobility, within the
      limits of the present experiment, obviously did not establish conditions which
      favoured an enhanced destruction of the periodontal tissues in the beagle dog
      model.

PMID- 8276979
TI  - Natural distribution of 5 bacteria associated with periodontal disease.
AB  - The purpose of this study was to determine the prevalence and distribution of 5
      bacterial pathogens in subgingival plaque, their relationship with each other and
      probing depth. Plaque was collected from 6905 sites in 938 subjects. A bacterial
      concentration fluorescence immunoassay and bacterial specific monoclonal
      antibodies were used to determine the presence and level of P. gingivalis (Pg),
      A. actinomycetemcomitans (Aa), P. intermedia (Pi), E. corrodens (Ec) and F.
      nucleatum (Fn) in each plaque sample. The prevalence in subjects was lowest for
      Pg (32%) and highest for Ec (49%). The site-based frequency distribution of these
      bacterial species ranged from 10.3% for Pg to 18.7% for Ec. Pi and Ec were the
      bacterial combination most often found together in a subject (27.2%). While 64.0%
      of the sites were without any of the 5 bacterial species evaluated, 20.2% had
      only 1 of the 5 bacterial species evaluated. The remaining 15.8% of sites had at
      least 2 bacteria species present. There was a general linear association of the
      detection level of bacterial species and probing depth. The odds ratios were 3.9
      (Pg), 3.0 (Aa), 4.0 (Pi), 2.7 (Ec) and 2.8 (Fn) of finding high levels of these
      bacterial pathogens at > 5 mm probing depth (p < or = 0.01). Mean probing depth
      at molar sites without a specific bacteria was greater (p < or = 0.01) in
      subjects with a specific bacterium compared to molar sites in subjects without
      the bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276980
TI  - Evaluation of the efficacy of interdental cleaning devices. How to design a
      clinical study.
AB  - A review of the literature was made, focusing on experimental designs used in
      clinical studies for assessment of the efficacy of interdental cleaning aids with
      regard to plaque removal and the prevention of caries and gingivitis. After
      careful consideration of the pros and cons of published procedures, an
      experimental design for such studies is proposed.

PMID- 8276981
TI  - Periodontal conditions of adult regular dental care attendants. A 12-year
      longitudinal study.
AB  - The purpose of the present study was to examine longitudinal alterations in the
      periodontal conditions of regular dental care attendants. 225 randomly selected
      patients (age 18-65 years) at 12 community dental clinics in the county of
      Varmland, Sweden, were subjected to a baseline clinical and radiographic
      examination in 1978 and to a re-examination in 1990. During the study period, all
      participants received preventive and therapeutic measures according to decisions
      made by the dentist on duty in the clinics. The examinations involved assessments
      of number of remaining teeth, plaque, gingivitis, probing pocket depth, loss of
      probing attachment and periodontal bone height. The results showed that during
      the 12 years of monitoring, an average of 0.4 teeth were lost. The % of tooth
      sites with gingivitis was lower in 1990 (4%) than in 1978 (15%), but no major
      changes were found for the mean probing pocket depth. The mean probing attachment
      loss during the 12 years amounted to 0.5 mm. The tooth site analysis revealed
      that buccal sites had experienced more loss of attachment than lingual and
      approximal surfaces. Whereas no differences were observed between age groups with
      respect to longitudinal loss of attachment at lingual and approximal tooth sites,
      the youngest age group demonstrated more pronounced loss at buccal surfaces than
      older subjects. The radiographic assessments of the alveolar bone height revealed
      a mean longitudinal loss amounting to 0.2-0.4 mm in the various age
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276982
TI  - The effect of systemic ibuprofen on gingival inflammation in humans.
AB  - This clinical trial investigated the influence of short-term ibuprofen therapy on
      the early phase of the treatment of adult chronic periodontitis. The subjects
      were 17 patients in good general health referred for specialist periodontal
      treatment, having moderate chronic adult periodontitis. A series of assessments
      were made every 2 weeks over an 8-week period, including evaluations of oral
      hygiene, gingival inflammation and probing pocket depths. All participants
      received oral hygiene instruction, and following baseline examinations, had half
      the dentition, chosen at random, treated by scaling and root planing. The
      patients were randomly distributed into 2 groups, a test group receiving a 14-day
      course of 800 mg ibuprofen daily, in 4 divided doses, and a control group who did
      not receive any drug regime. At the 2-week assessment following the drug regime,
      significantly greater reduction in gingival bleeding, colour and pocketing was
      detected in the test compared with the control group. The beneficial effects were
      less evident thereafter. Although clinical application of the regime used in this
      study would not be justified by these results, further research into anti
      inflammatory agents as an adjunct in the treatment of periodontal diseases could
      be considered, in the light of the beneficial effect on gingivitis in the early
      phase of periodontal treatment reported.

PMID- 8276983
TI  - The potential use of CO2-laser gingivectomy for phenytoin-induced gingival
      hyperplasia in mentally retarded patients.
AB  - Patients with hyperplastic states of the gingiva, i.e., phenytoin hyperplasia,
      nifedipine hyperplasia, cyclosporin hyperplasia, gingival fibromatosis and others
      may be treated by laser gingivectomy as no bone surgery is involved in these
      cases. Patients who are mentally retarded may represent special care problems
      postoperatively after conventional surgical gingivectomy i.e., unintentional
      removal of surgical dressing, postoperative bleeding etc. Therefore, the
      potential use of CO2-laser gingivectomy for mentally retarded persons was
      evaluated in a prospective study comprising 15 patients with fenytoin hyperplasia
      of the gingiva. No intra- or postoperative bleeding occurred and no surgical
      dressing was applied. The majority of the patients did not need any analgesics
      postoperatively. Healing was uncomplicated and the time needed for healing was of
      the same order of magnitude as after surgical gingivectomy.

PMID- 8276984
TI  - Flurbiprofen in the prevention and treatment of experimental gingivitis.
AB  - A clinical trial was undertaken to examine the effects of a potent cyclooxygenase
      inhibitor, flurbiprofen, on both developing and established gingivitis in humans.
      21 subjects with healthy gingiva abstained from all oral hygiene procedures for
      21 days. 7 subjects were prescribed flurbiprofen, 50 mg b.d. beginning from
      baseline and a control group (Cl, n = 14) were given placebo. Gingival redness
      and bleeding on probing were assessed at baseline, 7, 14 and 21 days. Crevicular
      fluid (GCF) samples were also taken to determine concentrations of PGE2, TxB2 and
      LTB4 at baseline and at 21 days. Results show that flurbiprofen significantly
      inhibited the development of redness and bleeding (p < 0.001) effects which were
      associated with a significant inhibition of TxB2 (p < 0.05). There were no
      apparent flurbiprofen effects on GCF-PGE2 or GCF-LTB4 during this 21-day
      gingivitis, model To assess the effects of flurbiprofen on established
      experimental gingivitis, the model was extended to 28 days. On day 21, the Cl
      group was subdivided into 2 groups of 7 subjects. One group was prescribed
      flurbiprofen (50 mg b.d.) for 7 days and controls (C2) continued to take placebo.
      All subjects continued to abstain from tooth cleaning. Pretreatment (day 21) and
      post-treatment (day 28) comparisons showed that flurbiprofen again significantly
      inhibited bleeding (p < 0.001), but did not affect redness. Control subjects
      demonstrated a significant elevation in gingival bleeding on day 28, and this was
      associated with significant rises in GCF-PGE2 (p < 0.001), GCF-TxB2 (p < 0.01)
      and GCF-LTB4 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8276985
TI  - Inter-relationships between bone mineral content measures. Dual energy
      radiography (DER) and bitewing radiographs (BWX).
AB  - In vitro periodontal alveolar bone mineral content (BMC) measurements obtained
      with dual-energy radiography (DER) were compared with assessments based on
      bitewing radiographs (BWX). In addition, in patients, the relationship between
      bitewing and several postcranial dual-energy-radiographic measures were
      evaluated. Dual-energy-radiographic and bitewing measurements were made on 2
      cadaver mandibles initially and after 2 incremental bone reductions at 4 sites.
      Rank-order correlations between dual-energy-radiographic and bitewing measures
      for the 4 sites ranged from 0.7 to 1.00. Bitewing measures indicated true bone
      loss with a sensitivity of 1.00. For patients, correlations between bitewing
      measures and dual-energy-radiographic scans suggested the strongest relationships
      were in the distal sections of the radius and ulna and in the intertrochanteric
      and Ward's areas of the femur. Correlations, in the 0.5-0.6 range, were not
      statistically significant (p > 0.05), but were quite robust considering the small
      sample size and preliminary nature of this investigation. Results suggest that
      the bitewing measure is sufficiently sensitive to detect clinically meaningful
      (5% or greater) changes in alveolar BMC and, further, that alveolar bone mineral
      content may reflect postcranial BMC. The implications of postcranial bone mineral
      changes being reflected in alveolar bone would enhance both our understanding and
      treatment of alveolar bone loss. The use of bitewing measures to facilitate
      identification of patients with postcranial bone loss is discussed.

PMID- 8276986
TI  - Specificity and levels of oral and systemic antibodies to Actinobacillus
      actinomycetemcomitans.
AB  - Salivary and gingival crevicular fluid antibodies and systemic antibodies were
      analysed for levels and specificity against Actinobacillus actinomycetemcomitans
      components. The major reactivity of salivary and serum IgA1 and IgA2 antibodies
      to the periodontal pathogen A. actinomycetemcomitans was against bands between 14
      and 83 kD for IgA1 and bands between 14 and 68 kD for IgA2 in Western blot. In
      addition to specific binding, there was also a hitherto unrecognized Fc-mediated
      binding of IgG antibodies to an A. actinomycetemcomitans component around 50 kD.
      Serum IgG antibodies to A. actinomycetemcomitans leukotoxin displayed the highest
      median value and only 1 individual showed salivary IgM antibodies in ELISA.
      Elevated levels of gingival crevicular fluid IgA2 antibodies indicated a local
      production of IgA from periodontal tissues. Using synthetic peptides, several
      distinct epitopes on the leukotoxin were recognized by both salivary and serum
      IgA antibodies.

PMID- 8276987
TI  - Periodontal health of the population in eastern Germany (former GDR).
AB  - The periodontal status of 1688 inhabitants of eastern Germany (former GDR) was
      investigated between July 1991 and March 1992, using the CPITN. The results show
      that only 1.4% of those examined have a healthy periodontal apparatus, whereas
      40.1% had some signs of severe periodontitis (CPITN 4). This implies a very high
      therapy requirement in all age-groups, with 93.1% of 15- to 19-year-olds in need
      of peridontal treatment (CPITN 1 + 2 + 3 + 4). A comparison between educational
      qualifications and frequency of brushing or routine dental checks reveals a
      better level of prophylaxis in the more educated classes. As expected, the CPITN
      code with good oral hygiene and regular dental checks was significantly lower
      than with poor oral hygiene and infrequent dental checks. The high prevalence of
      periodontal disease lends urgency to the development of an extensive prevention
      concept introduced in childhood.

PMID- 8276988
TI  - Patterns of projections from the pontine nuclei and the nucleus reticularis
      tegmenti pontis to the posterior vermis in the rhesus monkey: a study using
      retrograde tracers.
AB  - In an attempt to estimate the relative importance of the various afferent systems
      impinging on the oculomotor regions of the posterior cerebellar vermis of rhesus
      monkeys in quantitative terms, we made small injections of the retrograde tracers
      fast blue, fluorogold, and cholera toxin into different parts of a region of the
      posterior vermis, spanning lobuli VI through VIII. We found that the vast
      majority of cells retrogradely labeled by injections of lobulus VII and its
      vicinity lay in the pontine nuclei (PN), the nucleus reticularis tegmenti pontis
      (NRTP), and subnuclei a and b of the medial accessory olive. The remaining
      retrogradely labeled cells were distributed among a number of other brainstem
      nuclei or regions including the paramedian pontine reticular formation (PPRF). A
      quantitative analysis showed that the projection from the NRTP to the posterior
      vermis was focused on lobulus VII. While the projection from the PN as a whole
      demonstrated a preference for the more caudal parts of the posterior vermis, a
      closer look at the different regions of the PN revealed that cells located in the
      dorsal parts of the PN showed the same preference for lobulus VII as cells in the
      NRTP. The dorsal PN are a major gateway for cortical input to the cerebellum,
      related to visual processing and visually guided eye movements. Conversely, the
      NRTP, likewise involved in visually guided eye movements, is much more dependent
      on subcortical afferents. The observed convergence of input derived from the
      dorsal PN and the NRTP in oculomotor lobulus VII therefore suggests that a major
      function of this part of the vermis might be the integration of cortical and
      subcortical signals important for visually guided eye movements.

PMID- 8276989
TI  - Choline acetyltransferase-immunoreactive patches overlap specific efferent cell
      groups in the cat superior colliculus.
AB  - Fibers containing acetylcholine (ACh) form distinct patches in the dorsal
      intermediate gray layer (IGL) of the cat superior colliculus (SC). Although these
      patches are known to overlap several afferent projections to SC, it is not known
      whether they are associated with specific postsynaptic cell groups. We have
      examined the relationship of these ACh fiber patches to specific efferent cell
      groups by combining retrograde transport of horseradish peroxidase (HRP) with
      choline acetyltransferase (ChAT) immunocytochemistry. Successful HRP injections
      were made into the predorsal bundle (PB), the tecto-pontine-bulbar pathway (TPB)
      and the cuneiform region (CFR), the inferior olive (IO), the dorsolateral pontine
      gray nucleus (PGD), and the pedunculopontine tegmental nucleus (PPTN). The
      distribution of HRP-labeled neurons which project to these targets was mapped by
      a computer-based microscope plotter. Distinct clusters of HRP-labeled neurons in
      the IGL were seen after three injections into the mesencephalic reticular
      formation that involved the caudal TPB and cuneiform region (CFR), and after one
      injection into the medial accessory nucleus of IO. As many as seven clusters of
      labeled neurons were found in some sections through the caudal one-half of SC
      after the TPB/CFR injections. Each cluster consisted of 3-20 cells, all of which
      were small to medium in size. In sections also tested for ChAT, the cell clusters
      in the TPB/CFR cases were found to overlap precisely the ACh patches in the IGL.
      In addition, SC neurons projecting to the IO formed clusters above the ChAT
      patches and in the intermediate white layer (IWL) of SC. None of the other HRP
      injections produced any obvious cell clusters in the deep layers of SC. These
      results are the first to show that specific cell groups, distinguished by size
      and projection site, form clusters that match the patch-like innervation of
      cholinergic afferents to SC. This modular organization may correspond to saccade
      related cells that have also been reported to be organized into clusters in the
      cat SC.

PMID- 8276990
TI  - Chandelier cells in the hippocampal formation of the rat: the entorhinal area and
      subicular complex.
AB  - In the present study we describe the characteristics of the chandelier cells in
      the rat entorhinal cortex and subicular complex by using the Golgi method and
      combined Golgi-electron microscopic techniques. In the entorhinal cortex,
      chandelier cells were frequently stained in layers II/III. Two types of axonal
      complexes were noted. One had a preferential horizontal orientation and gave rise
      to terminals located in the upper portion of layers II/III. The second type of
      chandelier cell axon was observed in the medial entorhinal area, innervating the
      entire extent of layers II/III. In the subicular complex, chandelier cells were
      frequently stained in the parasubiculum, whereas only a few cells were found in
      the presubiculum. In both subfields, chandelier cell axons were restricted to
      layers II/III. In the subiculum, most chandelier cells were present in the
      stratum radiatum, giving rise to a descending axon that branched in the stratum
      pyramidale. Both the size and morphological features of the chandelier cell
      terminal portions were found to be region-specific. Electron microscopically, the
      cell body and dendrites of gold-toned chandelier cells displayed typical features
      of nonpyramidal cells, such as the presence of nuclear infoldings, symmetric and
      asymmetric synapses on the cell body, and moderate numbers of axon terminals
      covering the smooth dendritic surface. Five gold-toned chandelier cell axonal
      complexes were analyzed at the fine structural level. In all parahippocampal
      regions, gold-labeled axon terminals formed symmetric synaptic contacts with axon
      initial segments. Our results demonstrate the presence, morphological
      characteristics, and target selectivity of identified chandelier cells in the
      parahippocampal region of the rat. Together with previous data, these results
      suggest a wide distribution of this specialized type of cortical interneuron and
      indicate that it is a constant and essential component of inhibitory circuits in
      the cerebral cortex. The possible significance of chandelier cells for the
      circuits linking several subfields of the hippocampal formation is discussed.

PMID- 8276991
TI  - Connections of the auditory forebrain in the pigeon (Columba livia).
AB  - Ascending auditory efferents in birds terminate mainly within Field L2, a
      cytoarchitectonically distinct region of the caudomedial telencephalon. The
      organization of Field L2, and that of its flanking regions, L1 and L3, was
      investigated with 14C-2-deoxyglucose (14C-2-DG), cytochrome oxidase, and both
      retrograde and anterograde tracing techniques. Field L2 was found to contain a
      high concentration of cytochrome oxidase. Following auditory stimulation, 14C-2
      DG autoradiography revealed that Field L2 consists of two adjacent but seemingly
      discontinuous zones, designated Field L2a, which lies ventromedially, and Field
      L2b, which lies dorsolaterally. Termination of thalamic efferents: The thalamic
      auditory nuclei ovoidalis (Ov) and semilunaris parovoidalis (SPO) project
      predominantly upon Field L2, and possibly sparsely upon L1, L3 and the overlying
      hyperstriatum ventrale (HV). Ov subnuclei project upon L2a and SPO projects
      predominantly upon L2b. The topography of the projections is inverted along the
      ventromedial-to-dorsolateral axis of L2, and is in accord with an inverted
      tonotopic representation of frequencies; high frequencies (< 3.5 kHz) being found
      in the more ventromedial parts of L2a, and low frequencies and broad band
      responses in L2b. Intra- and extratelencephalic connections: Field L2a also
      receives a substantial projection from HV, but the efferent projections of L2a
      appear confined to adjacent "neostriatal" regions. The subsequent projections of
      L2b were not identified in this study. L1 and L3 project predominantly to the
      dorsal neostriatum (Nd) caudolateral to Field L, and have fewer projections to
      the caudomedial paleostriatum and anterior hyperstriatum accessorium. Nd projects
      massively upon the ventromedial nucleus of the intermediate archistriatum (Aivm),
      which has bilateral projections upon the caudomedial telencephalon and is the
      origin of a major descending pathway having dense terminations surrounding the
      ovoidalis complex (Ov and SPO), MLd, the lateral lemniscal nuclei, and sparse
      terminations within SPO itself. It is suggested that within the telencephalon the
      major components of the auditory pathway consist of cell groups which
      collectively correspond to the populations of neurons found within the auditory
      cortex of mammals.

PMID- 8276992
TI  - Spinal projections of pelvic visceral afferents of the rat: a calcitonin gene
      related peptide (CGRP) immunohistochemical study.
AB  - Little information is available concerning the pelvic visceral afferent system,
      in view of its terminal location in the spinal cord and its associated
      transmitter substances in the rat. By utilizing an immunostaining method to
      examine the transneuronal neurotransmitter depletion resulting from peripheral
      sensory nerve injury, the spinal projections of primary afferent fibers
      containing calcitonin gene-related peptide (CGRP) and originating from pelvic
      viscera were studied in the lumbosacral spinal cord of the rat. After unilateral
      or bilateral pelvic nerve section, CGRP immunoreactivity in the lumbosacral
      spinal cord was decreased greatly in the sacral parasympathetic nucleus (SPN),
      the dorsolateral fasiculus, the medial border of the dorsal horn, the dorsal gray
      commissure (DGC), and the intermediate gray connecting the SPN and DGC. Fine
      structural analysis showed that the CGRP-immunoreactive terminals made synaptic
      contact with dendrites and, rarely, with somata. Although there was some
      incidence of a synaptic contact between a CGRP-IR terminal and a vesicle
      containing profile, definite evidence of axo-axonal synapse has not been
      confirmed. These data indicate that CGRP-containing pelvic visceral primary
      afferent fibers project to autonomic areas of the lumbosacral spinal cord by way
      of the pelvic nerve and make synaptic contact with dendrites and somata.

PMID- 8276993
TI  - Ectopic Purkinje cells in the adult rat: olivary innervation and different
      capabilities of migration and development after grafting.
AB  - The abnormal location of large numbers of neurones is characteristic of genetic
      mutations which impair the migratory processes of developing nerve cells.
      Nevertheless, the presence of small amounts of ectopic neurones is a fairly
      common finding even in normal adult animals. The first aim of this study was to
      investigate a series of features of ectopic Purkinje cells in normal adult rats
      and particularly to assess whether these cells are still capable of interacting
      with their normal afferents. Several displaced Purkinje cells, identified by anti
      D28k calbindin immunolabelling as well as by typical morphological features, were
      present in the brainstem and cerebellum of all the examined animals. Two distinct
      morphological types of such cells could be recognized: 1) noncortical Purkinje
      cells, located in several areas of the dorsal brainstem and cerebellum,
      characterised by poorly developed and randomly oriented dendrites; and 2)
      cortical Purkinje cells, exclusively located in the dorsal cochlear nucleus,
      characterised by large dendritic trees oriented along parasagittal planes.
      Tracing experiments, in which Phaseolus vulgaris leucoagglutinin (PHA-L) was
      injected into the inferior olive, revealed that several ectopic Purkinje cells,
      belonging to both types, were contacted by the terminal arbours of olivary axons,
      structurally similar to cerebellar climbing fibres. On the basis of the
      observation that ectopic Purkinje cells were more frequent in the dorsal cochlear
      nucleus than in any other of the examined regions, we tested the hypothesis that
      this nucleus might represent a particularly favourable environment for the
      survival and development of Purkinje cells. By grafting embryonic cerebellar
      tissue in the fourth ventricle, only minimal migration of Purkinje cells into the
      recipient parenchyma was observed when the transplant was placed on the brainstem
      surface caudal to the cochlear nucleus. By contrast, when the graft was apposed
      to the latter nucleus, large numbers of Purkinje cells migrated and developed in
      its superficial layers. These Purkinje cells passed through all the different
      phases which characterise the normal ontogenesis of this neuronal population and
      finally developed mature structural features similar to those displayed by
      cortical ectopic Purkinje cells. This study demonstrates that at least some of
      the ectopic Purkinje cells receive their physiological olivary input. This fact
      indicates that Purkinje cells are able to attract olivary axons and establish
      specific connections, even if they are displaced in an abnormal environment. In
      addition, we show that the dorsal cochlear nucleus represents a particularly
      favourable environment for the survival and the development of Purkinje cells.

PMID- 8276994
TI  - Three-dimensional analysis of the dendritic domains of on- and off-cells in the
      rostral ventromedial medulla.
AB  - The rostral ventromedial medulla contains two classes of physiologically defined
      neurons, on-cells and off-cells, that are implicated in nociceptive modulation.
      In a continuing effort to detail the neural circuitry that underlies the activity
      of these two distinct neuronal types, the three-dimensional somatodendritic
      morphology of on- and off-cells was studied in the cat and the rat. Following
      physiological characterization with intracellular recording, on- and off-cells
      were injected with horseradish peroxidase and sectioned in the coronal plane.
      Their somatodendritic arborizations were reconstructed with the aid of a
      computerized three-dimensional reconstruction program. There were no differences
      between on- and off-cells in any somatodendritic feature analyzed. On- and off
      cells possess dendritic arbors that are elongated in the mediolateral axis
      relative to the dorsoventral and rostrocaudal axes. In the rat, the average
      dendritic extent was more than 1,400 microns mediolaterally but only about 800
      microns in either the dorsoventral or rostrocaudal axis. All somatic and
      dendritic measures were greater for both cat cells than for any rat neuron.
      Dendrites and their tips were located predominantly in regions lateral to the
      soma. The center of total dendritic length was usually located within 150 microns
      of the soma, most frequently ventral and lateral to the soma. The present results
      demonstrate that the dendritic domains of neurons in the nuclei raphe magnus and
      reticularis paragigantocellularis pars alpha are not contained within
      cytoarchitechtonic boundaries. On- and off-cell dendrites are interdigitated
      throughout the mediolateral extent of the rostral ventromedial medulla. Since on-
      and off-cell dendritic domains occupy a restricted rostrocaudal plane, afferents
      to the rostral ventromedial medulla that are confined to a single coronal plane
      and those that collateralize at several levels are likely to play different roles
      in the control of on- and off-cell activity.

PMID- 8276995
TI  - Prelunate, occipitotemporal, and parahippocampal projections to the basis pontis
      in rhesus monkey.
AB  - We used tritiated amino acids to study projections to the basilar pons from
      prestriate cortices in 18 rhesus monkeys to determine how connectional and
      functional heterogeneity of these regions are reflected in corticopontine
      circuitry. Fibers travelled with those from other parasensory associative
      cortices before terminating in the pontine nuclei. Prelunate projections were
      derived from area 19 (OA) at the medial convexity (including areas V3 and PO) and
      from the lateral convexity dorsal to the caudal tip of the Sylvian fissure
      (including areas DP and the dorsal part of area V4d). Pontine projections also
      arose from area 19 (OA), and areas TF, TL, and TH in the posterior aspect of the
      parahippocampal gyrus. No pontine projections arose from the prelunate convexity
      ventral to the caudal tip of the Sylvian fissure (ventral part of area V4d and
      area V4v), area TEO, the inferior temporal gyrus, or the lateral ventral temporal
      region. Terminations in the pons were distributed in the dorsolateral and lateral
      nuclei, and the lateral part of the peripeduncular nucleus. Medial convexity
      injections produced more extensive rostrocaudal pontine labeling, as well as
      terminations in the extreme dorsolateral nucleus and the nucleus reticularis
      tegmenti pontis. Dorsal prelunate injections had additional terminations in the
      ventral pontine nucleus. Posterior parahippocampal gyrus injections resulted in
      discrete label in the lateral and dorsolateral nuclei. Corticopontine projections
      destined for the cerebellum appear to be derived from extrastriate areas
      concerned mainly with visual spatial parameters, visual motion, and the
      peripheral field of vision, but not from areas subserving visual object
      identification and the central field of vision. Pontine afferents from the
      posterior parahippocampal gyrus may facilitate a cerebellar contribution to
      visual spatial memory, particularly when invested with motivational valence.

PMID- 8276996
TI  - Pigment-dispersing hormone-immunoreactive neurons in the nervous system of wild
      type Drosophila melanogaster and of several mutants with altered circadian
      rhythmicity.
AB  - Antisera against the crustacean pigment-dispersing hormone (beta-PDH) were used
      in immunocytochemical preparations to investigate the anatomy of PDH
      immunoreactive neurons in the nervous system of wild-type Drosophila melanogaster
      and in that of several brain mutants of this species, some of which express
      altered circadian rhythmicity. In the wild-type and in all rhythmic mutants
      (small optic lobes, sine oculis, small optic lobes; sine oculis), eight cell
      bodies at the anterior base of the medulla (PDFMe neurons) exhibit intense PDH
      like immunoreactivity. Four of the eight somata are large and four are smaller.
      The four large PDFMe neurons have wide tangential arborizations in the medulla
      and send axons via the posterior optic tract to the contralateral medulla. Fibers
      from the four small PDFMe neurons ramify in the median protocerebrum dorsal to
      the calyces of the mushroom bodies. Their terminals are adjacent to other PDH
      immunoreactive somata (PDFCa neurons) which send axons via the median bundle into
      the tritocerebrum. The results suggest a possible involvement of the PDFMe
      neurons in the circadian pacemaking system of Drosophila. The location and size
      of the PDFMe neurons are identical with those of neurons containing the period
      protein which is essential for circadian rhythmicity. Changes in the
      arborizations of the PDFMe neurons in small optic lobes; sine oculis mutants are
      suited to explain the splitting in the locomotor rhythm of these flies. In the
      arrhythmic mutant, disconnected, the PDFMe neurons are absent. The arrhythmic
      mutant per0, however, shows normal PDH immunoreactivity and therefore, does not
      prevent the expression of PDH-like peptides in these neurons.

PMID- 8276997
TI  - Nerve innervation of the hand and associated nerve dominance aggregates in the
      somatosensory cortex of a primate (squirrel monkey).
AB  - The cutaneous innervation territories of the median, ulnar, and radial nerves to
      the hand were determined from neurophysiological recordings of peripheral
      mechanoreceptor axons in adult squirrel monkeys. These territories were then
      related to cutaneous receptive fields of cortical area 3b neurons to determine
      how low-threshold inputs from each hand nerve map onto the primary somatosensory
      cortex. The results indicate that mechanoreceptor axons in each nerve innervate a
      continuous skin territory covering about 40% of the hand surface. The total
      territory of each nerve contains subregions of skin that are either autonomously
      innervated by that nerve or that receive overlapping innervation from more than
      one nerve. The autonomous, overlap, and total territories of each nerve are
      relatively constant from hand to hand. In the area 3b cortex, low-threshold
      afferents from each nerve provide inputs to aggregates of cortical neurons. The
      cortical aggregates relating to the median and ulnar nerves are arranged as
      continuous, rostrocaudally oriented bands, whereas aggregates relating to the
      radial nerve are discontinuous and more patch-like. Similar patterns of bands and
      patches, and similar compression ratios of skin/cortical area, are seen across
      different monkeys. These findings demonstrate that the primary somatosensory
      cortex of normal adult primates contains bands or patches of neurons that are
      dominantly activated by low-threshold inputs from specific hand nerves. This
      approach of delineating nerve territories and their related cortical dominance
      aggregates provides a useful means of analyzing cortical images of nerves and of
      quantitating peripheral and central patterns of deprivation after nerve injury.

PMID- 8276998
TI  - Distribution, morphological features, and synaptic connections of parvalbumin-
      and calbindin D28k-immunoreactive neurons in the human hippocampal formation.
AB  - Calcium binding proteins calbindin D28k (CaBP) and parvalbumin (PV) are known to
      form distinct subpopulations of gamma-aminobutyric acid (GABA)ergic neurons in
      the rodent hippocampal formation. Light and electron microscopic morphology and
      connections of these protein-containing neurons are only partly known in the
      primate hippocampus. In this study, CaBP and PV were localized in neurons of the
      human hippocampal formation including the subicular complex (prosubiculum,
      subiculum, and presubiculum) in order to explore to what extent these
      subpopulations of hippocampal neurons differ in phylogenetically distant species.
      CaBP immunoreactivity was present in virtually all granule cells of the dentate
      gyrus and population of in a proportion of pyramidal neurons in the CA1 and CA2
      regions. A distinct population of CaBP-positive local circuit neurons was found
      in all layers of the dentate gyrus and Ammon's horn. Most frequently they were
      located in the molecular layer of the dentate gyrus and the pyramidal layer of
      Ammon's horn. In the subicular complex pyramidal neurons were not immunoreactive
      for CaBP. In the prosubiculum and subiculum immunoreactive nonpyramidal neurons
      were equally distributed in all layers, whereas in the presubiculum they occurred
      mainly in the superficial layers. Electron microscopy showed typical somatic and
      dendritic features of the granule, pyramidal, and local circuit neurons. CaBP
      positive mossy fiber terminals in the hilus of the dentate gyrus and terminals of
      presumed pyramidal neurons of Ammon's horn formed asymmetric synapses with
      dendrites and spines. CaBP-positive terminals of nonprincipal neurons formed
      symmetric synapses with dendrites and dendritic spines, but never with somata or
      axon initial segments. PV was exclusively present in local circuit neurons in
      both the hippocampal formation and subicular complex. Most of the PV-positive
      cell bodies were located among or close to the principal cell layers. However,
      large numbers of immunoreactive neurons were also found in the molecular layer of
      the dentate gyrus and in strata oriens of Ammon's horn. PV-positive cells were
      equally distributed in all layers of the subicular complex. Electron microscopy
      showed the characteristic somatic and dendritic features of local circuit
      neurons. PV-positive axon terminals formed exclusively symmetric synapses with
      somata, axon initial segments and dendritic shafts, and in a few cases with
      dendritic spines. The CaBP- and PV-containing neurons formed similar
      subpopulations in rodents, monkeys, and humans, although the human hippocampus
      displayed the largest variability of these immunoreactive neurons in their
      morphology and location. Calcium binding protein-containing neurons frequently
      occurred in the molecular layer of the human dentate gyrus and in the stratum
      lacunosum-moleculare of Ammon's horn.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8276999
TI  - Prenatal exposure to ethanol alters the postnatal development and transformation
      of radial glia to astrocytes in the cortex.
AB  - Postmitotic neurons migrate from a zone(s) near the ventricles to the neocortex.
      During this migration, neurons associate with radial glia. After serving their
      role as guides for neuronal migration, the radial glia transform into astrocytes.
      Prenatal exposure to ethanol causes abnormal neuronal migration. We examined the
      effects of gestational exposure to ethanol on radial glia and astrocytes. Radial
      glia were stained immunohistochemically with the antibody RAT-401, and astrocytes
      were labeled with an antibody directed against glial fibrillary acidic protein
      (GFAP). The subjects were the offspring of rats fed an ethanol-containing liquid
      diet (Et), pair-fed a liquid control diet (Ct), or fed chow and water (Ch).
      During the first postnatal week, radial glial fibers (in Et-treated rats and
      controls) stretched from the ventricular surface through the developing cerebral
      wall to the pial surface. In the Et-treated rats, the radial processes were less
      dense and more poorly fasciculated than they were in the Ch- and Ct-treated rats.
      Moreover, by postnatal day (P) 5, there was a significant reduction in RAT-401
      immunostaining in the Et-treated rats, particularly in the superficial cortex. A
      similar reduction in control rats did not begin until P10. In all three treatment
      groups, GFAP-immunoreactive astrocytes were in the cortex throughout the period
      from P1 to P45. In neonates, GFAP-positive cells were distributed in the marginal
      zone (layer I) and the intermediate zone (the white matter). The number of GFAP
      positive cells in the cortical plate increased steadily with time so that, by
      P26, GFAP-immunoreactive astrocytes were distributed evenly through all cortical
      laminae. Interestingly, between P5 and P12, the number of astrocytes was
      significantly greater in Et-treated rats than in controls. Thus prenatal exposure
      to ethanol induces the premature loss of RAT-401-positive processes and the
      precocious increase in GFAP immunostaining. These ethanol-induced changes in
      glial development indicate that ethanol accelerates the transformation of radial
      glia into astrocytes. Moreover, the ethanol-induced premature degradation of the
      network of radial glial fibers may underlie the migration of late-generated
      neurons to ectopic sites.

PMID- 8277000
TI  - Evidence for a multi-compartmental histochemical organization of the nucleus
      accumbens in the rat.
AB  - In the present study, the compartmental organization of the nucleus accumbens was
      investigated by comparing the pattern of leu-enkephalin immunoreactivity with
      that of the opioid receptor ligand, naloxone, an established marker for the
      compartmental organization of the neostriatum. Both patterns have a
      nonhomogeneous, patch-like appearance throughout the rostrocaudal extent of the
      nucleus and show a good, mutual correspondence. In the core of the nucleus
      accumbens as well as in the border region between the nucleus accumbens and the
      caudate-putamen, leu-enkephalin-rich areas are in register with opioid receptor
      dense areas. In the shell region the precise relationship between the enkephalin
      and the naloxone patterns could not be established. A comparison of the
      connectivity patterns and neurochemical characteristics of the opioid receptor
      dense compartments in the nucleus accumbens with those in the caudate-putamen
      reveals major discrepancies between these two striatal subdivisions. We therefore
      conclude that, rather than a bicompartmental patch/striosome-matrix organization,
      the nucleus accumbens has a multicompartmental organization.

PMID- 8277002
TI  - FMRFamide-like activity in the female locust during vitellogenesis.
AB  - The control of oviposition in the locust involves the expulsion of eggs from the
      lateral oviducts, a process believed to be under neurohormonal control. In this
      paper we have attempted to identify this putative hormone. Immunohistochemical
      staining of the brain retrocerebral complex and suboesophageal ganglion of
      Locusta migratoria with antiserum against FMRFamide revealed a number of
      FMRFamide-immunopositive cells. FMRFamide-like immunoreactivity was present in
      median neurosecretory cells and lateral neurosecretory cells of the
      protocerebrum. Other FMRFamide-immunoreactive cells were detected in the
      deutocerebrum and tritocerebrum. Immunoreactive cell processes were observed in
      the mushroom bodies, the central body, the optic lobes, and in the axon tracts
      leaving the pars intercerebralis and tritocerebrum. FMRFamide-like material was
      also seen in the circumoesophageal commissures. Further FMRFamide-like material
      was present in cell bodies of the suboesophageal ganglion. FMRFamide-like
      staining activity changed dramatically during the oviposition cycle in mature
      adult females. The median neurosecretory cells stained lightly immediately after
      oviposition and remained pale until the third day, when staining of perikarya and
      axon tracts increased. The staining intensity decreased on days 4 and 5. The
      titre of FMRFamide-like material in the hemolymph increased during the
      vitellogenic cycle but plummeted after oviposition. A single band of FMRFamide
      like material was evident on immunoblot following sodium dodecyl sulphate
      polyacrylamide gel electrophoresis of adult female hemolymph. The approximate
      molecular weight of this molecule was 8,000. Gel permeation chromatography of
      hemolymph revealed a FMRFamide-immunoreactive fraction with a molecular weight of
      8,000. This fraction possessed myotropic activity when applied to the locust
      oviduct.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277001
TI  - Age-related effects of nerve growth factor on the morphology of embryonic sensory
      neurons in vitro.
AB  - Studies of neonatal and adult mammals have shown that neuronal morphology is
      regulated in part by the availability of target-derived neurotrophic factor. To
      test whether the same is true for embryonic neurons, which are dependent on
      target-derived neurotrophic factors for survival, we grew neural crest-derived
      sensory neurons from the trigeminal ganglion of avian embryos of different ages
      in vitro in different concentrations of nerve growth factor (NGF) and measured
      the number of branch points and total length of the resulting arborizations.
      Although the size and complexity of arborizations increased with embryonic age up
      to embryonic day (E)14, neuronal morphology for embryos younger than E14 was
      unaffected by the concentration of NGF in the culture medium. However, beginning
      at E14, the stage at which trigeminal neurons start to lose their absolute
      requirement for NGF for survival, the neurons had significantly more branch
      points and larger arborizations in higher concentrations of NGF. Thus, it appears
      that the extent of neurite outgrowth in young embryos is independent of
      neurotrophic factor concentration; each neuron that receives enough neurotrophic
      factor to survive elaborates approximately the same size arbor. As trigeminal
      neurons mature and become less dependent on neurotrophic factor for survival,
      they acquire the ability to respond to neurotrophic factor with increased neurite
      growth and branching, as in neonates and adults.

PMID- 8277003
TI  - Vasopressin and oxytocin gene expression in the human hypothalamus.
AB  - We studied the distribution of messenger ribonucleic acids coding for vasopressin
      and oxytocin in the human hypothalamus by means of hybridization histochemistry.
      Numerous large and medium-sized neurons contain vasopressin messenger ribonucleic
      acid in the paraventricular nucleus, supraoptic nucleus, and accessory
      magnocellular nucleus. Small, lightly labeled vasopressin neurons also were
      detected in the suprachiasmatic nucleus. In addition, a relatively sparse band of
      mostly ovoid, medium-sized vasopressin neurons mingle with unlabeled neurons of
      the lateral hypothalamic area; these cells extend dorsoventrally from the region
      ventral to the stria terminalis to the ventrolateral hypothalamus, sometimes
      transgressing the boundaries of nearby nuclei. We did not detect vasopressin gene
      expression in neurons of the bed nucleus of the stria terminalis proper, although
      some of the dorsal-most labeled neurons of the lateral hypothalamus extend into
      the region of the caudal bed nucleus. Some lateral hypothalamic neurons also
      encroach upon other extrahypothalamic structures, such as the zona incerta. The
      nucleus basalis of Meynert complex was, with only rare exceptions, devoid of
      cells containing vasopressin messenger ribonucleic acid. Oxytocin messenger
      ribonucleic acid is found in the supraoptic nucleus, paraventricular nucleus,
      accessory magnocellular nucleus and, less frequently, in neurons of the lateral
      hypothalamus. In the hypothalamic magnocellular nuclei, oxytocin neurons are
      somewhat smaller than vasopressin neurons. Vasopressin cells outnumber oxytocin
      cells in the supraoptic nucleus, but their numbers are comparable in the
      paraventricular nucleus. As with vasopressin neurons, lateral hypothalamic
      oxytocin cells loosely span several diencephalic nuclei and encroach occasionally
      upon adjacent regions. These results confirm that the organization of vasopressin
      and oxytocin neurons in the human hypothalamus is largely comparable to that in
      nonhuman species and demonstrate the utility of hybridization histochemistry for
      elucidating the chemoarchitecture of the human brain.

PMID- 8277004
TI  - Terminal arborizations of olfactory nerve fibers in the glomeruli of the
      olfactory bulb.
AB  - The glomerulus of the olfactory bulb may serve as a fundamental organizational
      unit for odor representation. In this context, the axons of olfactory receptor
      cells with similar response spectra may converge in specific glomeruli. While the
      topography between the olfactory epithelium and the olfactory bulb glomeruli has
      been explored, the characteristics of primary afferent terminal fields within
      glomeruli are poorly understood. To explore this issue, reconstructions of the
      terminal arbors of single olfactory nerve (ON) fibers within glomeruli were
      carried out in the rat olfactory bulb at the light microscopic level. Tissue
      samples prepared with the Golgi-EM technique resulted in distinct impregnation of
      limited subsets of individual ON fibers. Following camera lucida reconstruction,
      quantitative analyses were made on selected sets of ON fibers and on the
      glomeruli they invaded. Most ON fibers began to arborize only after penetrating
      the glomeruli to a mean depth of approximately 35.9 microns. The fibers gave rise
      to a complex arbor of branches that was limited in total length (mean 157.7
      microns) and the number of en passant varicosities or terminal enlargements (mean
      = 8.1). The number of varicosities and terminal boutons was proportional to the
      total length of branches. Also, there was a statistically significant correlation
      between the total branch length and the area (microns2) encompassed by the total
      arbor. The intraglomerular region supplied by the terminal arbor of an individual
      ON fiber was generally restricted. Given the recent molecular specificity
      attributed to olfactory receptor cells, this may provide a morphological basis
      for selective processing of signals encoded by specific receptors in the
      olfactory epithelium.

PMID- 8277005
TI  - Visual projections induced into the auditory pathway of ferrets: II.
      Corticocortical connections of primary auditory cortex.
AB  - Although the development of corticocortical projections has been well studied,
      less is known about the role of sensory inputs in the specification of these
      connections. As part of an ongoing series of studies in our laboratory, we have
      examined the role of thalamic input modality in the development of
      corticocortical connections. These studies involve making unilateral lesions and
      inducing retinal inputs into the auditory thalamus (MGN) during early development
      in ferrets, thereby conferring visual responsiveness on primary auditory cortex
      (AI). In this way we can examine the role of input identity in cortical
      specification in general, and connectivity patterns specifically. A previous
      paper (Pallas et al. [1990] J. Comp. Neurol. 298:50-68) described the pattern of
      thalamocortical and corticothalamic connections of auditory cortex in normal and
      lesioned animals. This study compares the pattern of auditory corticocortical
      connections in normal and lesioned animals. We injected neuroanatomical tracers
      into AI and mapped out the distribution of retrogradely labelled cells in the
      cortex. We report that the cortical inputs to ferret AI resembled those in cats,
      and that the pattern of ipsi- and contralateral corticocortical connections of
      ferret AI with visual input was similar to the normal pattern. Auditory cortex
      with visual input did not make ectopic connections with visual cortex, but
      maintained its connections with other auditory cortical areas. These results
      suggest that the overall corticocortical connections of an area are not
      influenced by the modality or activity pattern of its inputs. In particular,
      altering the input activity to a cortical area does not seem to promote the
      formation of entirely new connections, although small changes in the strength of
      existing connections are possible (Sur et al. [1990] Trends Neurosci. 13:227
      233).

PMID- 8277006
TI  - Reorganization of mossy fiber synapses in male and female hypothyroid rats: a
      stereological study.
AB  - Thyroid hormone deficiency has been reported to interfere with synaptogenesis,
      particularly in those regions of the brain where the neurons display a late and
      protracted histogenesis, although the extent of the synaptic alterations remains
      unknown. To provide detailed quantitative data on the effects of hypothyroidism
      upon synapses, a link of the hippocampal circuitry was selected: the contact
      between mossy fibers and dendritic excrescences of CA3 pyramidal cells (MF-CA3
      synapses). Groups of six male and six female rats aged 30 and 180 days were
      analyzed separately after being treated as follows: (1) hypothyroid from day 0
      until day 30 (30 day old hypothyroid group); (2) hypothyroid from day 0 until day
      180 (180 day old hypothyroid group); (3) hypothyroid until day 30 and thenceforth
      maintained euthyroid (recovery group); and (4) and (5) 30 and 180 day old control
      groups, respectively. Timm staining, Golgi impregnation, and electron microscopy
      were employed to estimate the volume of the mossy fiber system, the number and
      size of mossy fiber boutons, and the number and related features of MF-CA3
      synapses. The volume of the mossy fiber system and the number of synaptic boutons
      were reduced in all experimental groups. The total number of synapses was
      decreased in 30 day old hypothyroid rats, but did not differ among 180 day old
      animals. Postsynaptic densities were shorter in hypothyroid and recovery groups
      than in controls, although the reduction was not as marked in recovery rats as it
      was in hypothyroid animals. Structural alterations were noted in the pre- and
      postsynaptic compartments of MF-CA3 synapses of both 180 day old hypothyroid and
      recovery rats. These changes can be regarded as mechanisms of reorganization as
      they underlie the compensation for the hypothyroid-induced numerical reduction of
      synapses observed in 30 day old animals and enable a complete catch-up of their
      total number. However, synaptic reorganization was not fully achieved, as
      revealed by the reduction in the size of the synaptic sites in hypothyroid and
      recovery animals. Finally, we demonstrate that hypothyroidism did not interfere
      with the sex-related differences of MF-CA3 synapses described in normal rats.

PMID- 8277007
TI  - Keratoacanthoma.
AB  - The keratoacanthoma is a common cutaneous neoplasm that most often occurs on sun
      exposed sites in light-skinned persons of middle age or older. It is considered
      the prototype of cutaneous pseudo-malignancies because it is a rapidly growing
      tumor with a histologic pattern resembling squamous cell carcinoma. It may be
      best viewed as an aborted malignancy that only rarely progresses into an invasive
      squamous cell carcinoma. It is most likely derived from hair follicle cells. The
      common type of keratoacanthoma and its many variants are discussed with emphasis
      on clinical and histologic features, biologic behavior, and response to therapy.

PMID- 8277008
TI  - Classification of pseudoxanthoma elasticum: report of a consensus conference.

PMID- 8277010
TI  - Clinical pearl: deriving maximum information from skin biopsy specimens of
      inflammatory dermatoses.

PMID- 8277009
TI  - Hepatitis, HIV, and the dermatologist: a risk review.
AB  - The practice of dermatology has always carried with it the risk of patient
      acquired infection. This review covers health risks associated with the care of
      HIV-infected patients and patients who are chronic carriers of hepatitis B or C
      virus, protection options to reduce exposure, and protocols should exposure
      occur. Hepatitis B continues to be a major risk to health care workers, killing
      approximately 200 per year. In contrast, as of 1990, only 327 total health care
      personnel had acquired HIV, with no deaths reported. Data are lacking regarding
      hepatitis C, but it appears to be an increasing concern. Needlesticks are the
      most common form of occupational transmission, with an infectivity rate of 30%
      for hepatitis B, 3% for hepatitis C, and 0.3% for HIV. Universal precautions are
      the cornerstones of safety. Hepatitis B vaccination, zidovudine prophylaxis, and
      hepatitis C therapy are discussed as postexposure recommendations are reviewed.

PMID- 8277011
TI  - Surgical pearl: the retraction suture.

PMID- 8277012
TI  - Blue gingiva, an unusual oral pigmentation resulting from gingival tattoo.

PMID- 8277013
TI  - Syringocystadenoma papilliferum mimicking basal cell carcinoma.

PMID- 8277014
TI  - Proximal white subungual onychomycosis: a sign of immunodeficiency.

PMID- 8277015
TI  - Linear psoriasis associated with systemic lupus erythematosus.

PMID- 8277016
TI  - Primary anetoderma associated with the antiphospholipid syndrome.

PMID- 8277017
TI  - Peeling skin syndrome.

PMID- 8277018
TI  - Evaluation of muscles in a patient with suspected amyopathic dermatomyositis by
      magnetic resonance imaging and phosphorus-31-spectroscopy.

PMID- 8277019
TI  - Acne rosacea as a cutaneous manifestation of HIV infection.

PMID- 8277020
TI  - Mixed cryoglobulinemia and hepatitis C virus infection.

PMID- 8277021
TI  - Acute miliary tuberculosis of the skin in AIDS.

PMID- 8277022
TI  - Granulocyte-macrophage colony-stimulating factor and psoriasis.

PMID- 8277023
TI  - Treatment of generalized bullous pemphigoid with oral tetracycline.

PMID- 8277025
TI  - Ichthyosis. Basal cell carcinoma. Granuloma annulare. Self-assessment examination
      of the American Academy of Dermatology.

PMID- 8277024
TI  - Dermatophytosis in lesions of disseminated superficial actinic porokeratosis.

PMID- 8277026
TI  - Mantle zone lymphoma: an immunohistologic study of skin lesions.
AB  - BACKGROUND: Mantle zone lymphoma (MZL) is a B-cell proliferation regarded as the
      follicular variant of intermediate lymphocytic lymphoma (ILL). Neoplastic small
      lymphoid cells proliferate as wide mantles around atrophic centers of benign
      appearance. OBJECTIVE: The clinical, histologic, and immunohistochemical features
      of four cases of MZL, heralded by cutaneous lesions, are described and correlated
      with the lymph node pattern. RESULTS: All specimens showed extensive nodules in
      the reticular dermis invading the subcutaneous tissue. They were mainly composed
      of a proliferation of small lymphocytes with slightly irregular nuclear contours
      and clumped chromatin, forming wide mantles around small atrophic germinal
      centers. Serial biopsy specimens in case 1 revealed evolution of the skin lesions
      from pseudolymphoma into MZL. Their immunohistochemistry was similar to that of
      lymph nodes and showed that the neoplastic cells were CD5+, CD20+, CD22+, CD25+,
      CD74+, Leu-8+, HLA-DR+, IgM+, IgD+ with restriction for the lambda light chain,
      CD10-, and CD71-, whereas the germinal center cells were polyclonal. In three
      cases many CD38+, PCA-1+ plasma cells were present both in the grenz zone and in
      bordering neoplastic nodules. The clinical course was chronic. The only death
      occurred from unrelated causes; one patient is still alive 17 years after onset.
      CONCLUSION: Skin lesions may be the only manifestation of MZL for an extended
      period. The differentiation between pseudolymphoma and other lymphoma subtypes is
      based not only on the histologic and cytologic features but also on the
      architecture, followed by immunohistochemical confirmation.

PMID- 8277027
TI  - A new clinical disorder of twisted and rolled body hairs with multiple, large
      knots.
AB  - BACKGROUND: We present a new hair disorder characterized by an unusual twisting
      and matting of body hairs. This disorder may occur as an acquired or, possibly,
      an inherited trait. OBJECTIVE: Our purpose was to analyze the clinical features
      of three patients and report the changes revealed by light microscopy and
      scanning electron microscopy. METHODS: We examined two unrelated adults with
      acquired multiple large knots of body hairs and a newborn infant with a familial
      history of the same entity. RESULTS: In the two adults the hairs were rolled and
      knotted together, and twisting of body hairs occurred in areas where rubbing was
      frequent. In the familial type, which was suggestive of an autosomal dominant
      inheritance pattern, no mechanical explanation could be found. Light microscopy
      confirmed the clinical impression of twisted and felted hairs, and scanning
      electron microscopy revealed sticking of at least 20 hairs. No underlying skin
      disease or deeper process was found. CONCLUSION: Multiple twisted and rolled body
      hairs that may develop into multiple, large knots may appear as a minor variant
      of hair matting or felting. Scanning electron microscopy shows multiple hairs
      that originate from different hair follicles and roll and stick together
      centrally.

PMID- 8277028
TI  - The prevalence of childhood atopic eczema in a general population.
AB  - BACKGROUND: Atopic eczema has become more common during recent decades, but few
      studies have looked at its prevalence in the general community. OBJECTIVE: Our
      purpose was to ascertain the prevalence of atopic eczema, its age of onset, and
      its relationship to breast-feeding and ear piercing in a general practice
      population. METHODS: Children (N = 1104), aged 3 to 11 years, were identified
      from a computerized register in a socially and ethnically mixed English general
      practice population of 13,314. Of these, 1077 children (97.6% recruitment) were
      interviewed with parents or guardians, and the resultant data were recorded on a
      survey form. RESULTS: The lifetime occurrence of atopic eczema was 20% in boys
      (12% in the past year) and 19% in girls (11% in the past year). Prevalence in the
      past year was 10% to 14% in boys aged 3 to 11 years but fell in girls from 15% at
      3 to 5 years to 8% at 9 to 11 years. Atopic eczema developed in the first 12
      months of life in 60% of the children who had the condition, and it developed in
      the first 6 months of life in three quarters of these children. Ear piercing had
      been performed in 35% of girls and 3% of boys and was most prevalent in social
      classes 3, 4, and 5. More than half the girls aged 9 to 11 years had pierced
      ears. Breast-feeding did not affect the prevalence of atopic eczema. CONCLUSION:
      The lifetime prevalence of atopic eczema was 20% in children aged 3 to 11 years.
      There was no evidence that ear piercing perpetuated eczema in this age group.
      Breast-feeding did not protect against the development of atopic eczema.

PMID- 8277029
TI  - Sunlight: a major factor associated with the development of melanocytic nevi in
      Australian schoolchildren.
AB  - BACKGROUND: Case-control studies have identified melanocytic nevi (MN) as the
      most important phenotypic risk factor for melanoma. A knowledge of any
      environmental factors that cause MN may facilitate prevention of melanoma.
      OBJECTIVE: This study was undertaken to explore the possible role of ambient
      solar irradiation in the development of MN in children. METHODS: With a standard
      protocol developed after international consultation, the same medical observers
      examined children in three Australian cities (Melbourne, Sydney, and Townsville)
      that span a wide range of latitude. RESULTS: A total of 1123 Australian
      schoolchildren 6, 9, 12, and 15 years of age were surveyed. Larger numbers of MN
      were found (mean 65.4 MN, standard deviation 52.9) than in previous studies of
      children. Prevalence increased with diminishing latitude (51.1 in Melbourne, 66.5
      in Sydney and 77.2 in Townsville), particularly in children 6 and 9 years of age.
      Although nevus numbers were higher in children with light skin and hair, blue
      eyes, and freckling, the latitude gradient remained after adjustment for these
      and other factors in multivariate analysis. CONCLUSION: Latitude of residence,
      and by implication ambient UV radiation, is strongly related to nevus prevalence
      in young Australian children. However, these differences diminish with age and
      may disappear by 15 years of age.

PMID- 8277030
TI  - Cultivation of Borrelia burgdorferi from the blood of two patients with erythema
      migrans lesions lacking extracutaneous signs and symptoms of Lyme disease.
AB  - BACKGROUND: We recently demonstrated that cultivation of Borrelia burgdorferi
      from skin biopsy specimens obtained from erythema migrans lesions was an
      efficacious procedure to confirm the diagnosis of Lyme disease. OBJECTIVE: Our
      purpose was to investigate the efficacy of our microbiologic technique on blood
      samples obtained from patients with Lyme disease and erythema migrans. METHODS:
      Whole blood samples were obtained from 52 patients with erythema migrans and
      early localized or early disseminated Lyme disease and placed into polystyrene
      tubes containing 6 ml of modified Barbour-Stoenner-Kelly medium, processed, and
      examined for B. burgdorferi by dark-field microscopy. RESULTS: B. burgdorferi was
      cultured from the blood of two of our 52 patients (4%). Clinically, both of these
      patients were considered to have early localized Lyme disease. CONCLUSION: The
      culture of B. burgdorferi from the blood of patients with early Lyme disease does
      not appear to be an efficacious procedure to confirm the diagnosis of Lyme
      disease. However, the demonstration of spirochetemia in patients with erythema
      migrans without any extracutaneous evidence of disseminated illness does have
      therapeutic significance.

PMID- 8277031
TI  - Genetic susceptibility to fixed drug eruption: evidence for a link with HLA-B22.
AB  - BACKGROUND: Our observation of familial cases of fixed drug eruption (FDE)
      prompted us to consider a genetic predisposition to this disease. OBJECTIVE: Our
      purpose was to determine whether there is any association between FDE and any of
      the major histocompatibility complex class I or II alleles. METHODS: HLA class I
      and II typing was performed by lymphocytotoxicity assay in 36 unrelated patients
      with FDE. RESULTS: Significantly higher (p < 0.0001) frequencies of the B22 and
      Cw1 antigens were found in the 36 patients with FDE. CONCLUSION: Our data are the
      first to suggest a genetic predisposition to FDE.

PMID- 8277032
TI  - Bubble hair. Case caused by an overheating hair dryer and reproducibility in
      normal hair with heat.
AB  - BACKGROUND: Bubble hair is an acquired hair shaft deformity characterized by
      bubble-like areas in the hair shaft seen with light microscopy and corresponding
      cavitary defects with scanning electron microscopy. OBJECTIVE: Our purpose was to
      report the fourth case of bubble hair, to demonstrate a cause, and to determine
      whether the cavities contain gas or liquid. METHODS: Light and scanning electron
      microscopy were performed. The patient's hair dryer was examined. We applied heat
      to normal hair of the patient and that of 16 human volunteers. Approximate
      temperatures for bubble formation were measured. The bubble contents were
      investigated by applying aqueous and nonaqueous liquids to affected hairs.
      RESULTS: No person's hair failed to develop bubbles when subjected to sufficient
      heat. The cause of bubble hair in the patient was an overheating hair dryer. The
      cavitations contained a gas. CONCLUSION: Bubble hair is a reproducible hair shaft
      defect caused by heat. The use of overheating hair dryers, or any other hair care
      equipment that overheats, should be avoided.

PMID- 8277033
TI  - Histologic evaluation of chronic human wounds treated with hydrocolloid and
      nonhydrocolloid dressings.
AB  - BACKGROUND: Studies of acute surgical wounds in pigs have shown granulomatous
      tissue reactions induced by hydrocolloid dressings. OBJECTIVE: We examined biopsy
      specimens from chronic wounds in humans treated with hydrocolloid or
      nonhydrocolloid dressings to determine whether such reactions occurred. METHODS:
      A blinded retrospective analysis of 22 chronic ulcer biopsy specimens from 22
      patients was performed by two dermatopathologists independently. RESULTS: No
      differences were seen between hydrocolloid-treated and non-hydrocolloid-treated
      wounds. Granulation tissue was seen in all specimens. No cavities, eosinophilic
      inclusions, polarizable material, or multinucleated giant cells were identified.
      CONCLUSION: There are no significant histologic differences between hydrocolloid
      treated and non-hydrocolloid-treated wounds in humans.

PMID- 8277034
TI  - The sensitivity and specificity of direct immunofluorescence testing in disorders
      of mucous membranes.
AB  - BACKGROUND: Direct immunofluorescence testing is frequently used to diagnose
      inflammatory mucosal disorders, but its accuracy relative to histologic and
      clinical diagnosis has not been reported. OBJECTIVE: Our purpose was to compare
      diagnoses made on the basis of direct immunofluorescence, histologic features,
      and clinical impression and define optimal immunofluorescence criteria. METHODS:
      Direct immunofluorescence findings and diagnostic impressions for 500 unselected
      mucosal biopsy specimens were recorded, as were the histologic diagnosis, initial
      clinical impression, and final diagnosis made on the basis of all studies and
      follow-up. Sensitivity and specificity were calculated for each parameter by
      diagnosis and site. RESULTS: Direct immunofluorescence testing was superior for
      diagnosing pemphigus and pemphigoid and was slightly inferior to histologic
      evaluation for diagnosing lichen planus. Optimal criteria were IgG and C3
      intercellular substance staining for pemphigus, linear C3 basement membrane zone
      deposits for pemphigoid, and shaggy fibrinogen basement membrane zone staining
      plus IgM cytoids for lichen planus. Direct immunofluorescence testing was
      diagnostic for several extraoral mucosal biopsy specimens. CONCLUSION: Direct
      immunofluorescence is a valuable diagnostic tool for diseases of the oral mucosa
      and other mucosal sites.

PMID- 8277035
TI  - Topical tretinoin (retinoic acid) treatment of hyperpigmented lesions associated
      with photoaging in Chinese and Japanese patients: a vehicle-controlled trial.
AB  - BACKGROUND: Hyperpigmented lesions are a predominant component of photoaging in
      Chinese and Japanese persons. Topical 0.1% tretinoin cream improves the
      hyperpigmentation associated with photoaging in Caucasian persons. OBJECTIVE: Our
      purpose was to assess the efficacy of 0.1% tretinoin cream treatment of
      hyperpigmented lesions associated with photoaging in Chinese and Japanese
      patients. METHODS: Forty-five photoaged patients (23 Chinese, 22 Japanese)
      completed a double-blind, randomized study in which 21 applied 0.1% tretinoin
      cream and 24 applied vehicle cream once daily to face and/or hands for 40 weeks.
      Patients' hyperpigmented lesions were evaluated clinically and by colorimetry
      throughout the study and by histologic analysis of skin biopsy specimens taken
      before therapy and at the end of treatment. RESULTS: At the end of treatment,
      hyperpigmented lesions of the face and hands were lighter or much lighter in 90%
      of patients receiving tretinoin compared with 33% receiving vehicle (p < 0.0001).
      Colorimetry demonstrated significant lightening of lesions after tretinoin
      compared with vehicle (p < 0.05). Histologic analysis of hyperpigmented lesions
      demonstrated a statistically significant 41% decrease in epidermal pigmentation
      with tretinoin therapy as compared with a 37% increase in the vehicle group (p =
      0.0004). No patient withdrew for adverse effects. CONCLUSION: By clinical,
      colorimetric, and histologic evaluation, 0.1% tretinoin cream significantly
      lightens the hyperpigmentation of photoaging in Chinese and Japanese patients.

PMID- 8277036
TI  - Dohi Memorial Lecture. The skin as an immunological organ: allergic contact
      dermatitis as a paradigm.

PMID- 8277037
TI  - Clinical hair loss: diagnosis and treatment.

PMID- 8277038
TI  - Metastatic behavior and tumorigenicity of a human melanoma cell line (MM-RU)
      after injection into nude mice.
AB  - The ability of the human amelanotic melanoma cell line MM-RU to produce
      experimental metastases and to grow tumors at subcutaneous inoculation sites in 4
      week-old nude mice was examined. After i.v. inoculation of 10(6) cells, all
      injected mice (n = 21) developed consistent numbers of metastatic pulmonary
      colonies within 32 days. The coefficients of variation for the number of colonies
      were between 17%-23% in three independent experiments. Survival time after i.v.
      inoculation was 63 +/- 7 days (mean +/- SD) (n = 20). Within 20 days,
      subcutaneous inoculation of 5 x 10(6) cells resulted in tumor growths of 13 +/- 3
      mm (mean +/- SD) at the inoculation sites in all nude mice (n = 12). The MM-RU
      cell line seems to be a simple, fast vehicle for testing the effect of melanoma
      growth modulators on experimental pulmonary metastases as well as on
      subcutaneously growing melanoma.

PMID- 8277039
TI  - Macrophage markers 25F9 and 27E10 on human keratinocytes in normal and diseased
      skin.
AB  - In the present study, an immunohistochemical analysis was made of the expression
      pattern of different macrophage markers such as 25F9, 27E10 and RM 3/1 on the
      surface of human keratinocytes (HK) in biopsies obtained from healthy volunteers
      and from patients with lichen planus, chronic cutaneous graft-versus-host
      reaction, mycosis fungoides, and purpura pigmentosa chronica. In biopsies from
      the healthy volunteers and from both clinically involved and uninvolved skin of
      the patients, the HK of the basal cell layer exhibited a specific peroxidase
      positive reaction when the monoclonal antibody against 25F9 was used. Lesional HK
      from all patients studied displayed 25F9 and 27E10 in nearly the entire
      epidermis. The present findings provide further evidence that HK and macrophages
      share a number of common cell surface moieties.

PMID- 8277040
TI  - Pilary complex carcinoma: an adnexal carcinoma of the skin with differentiation
      towards the components of the pilary complex.
AB  - We report twelve cases with a distinctive form of adnexal carcinoma occurring
      most commonly over the head and neck of relatively old individuals. The growth
      was single in all cases, deep dermal in location, and consisted of massive
      proliferation of small basaloid cells with only occasional connection with the
      surface epidermis. The basaloid tumor masses showed only a few areas of
      palisading of their outer cell nuclei and occasional retraction space formation.
      The neoplasm revealed scattered areas of trichilemmal and epidermoid
      keratinization, foci of sebaceous, and areas of sweat ductal differentiation
      indicating participation of various components of the pilary complex.

PMID- 8277041
TI  - Multiple agminated juvenile melanoma arising on a hyperpigmented macule.
AB  - A case of multiple agminated juvenile melanoma (MAJM) arising on a hyperpigmented
      macule is reported. The patient, a 1-year-old boy, had 9 small nodules on an
      irregular, hyperpigmented macule on the right shoulder. Histologically, the
      nodules contained nests of spindle-shaped cells in their epidermis and at the
      dermoepidermal junction, and the hyperpigmented macule exhibited increased
      melanin granules in the basal layer and small nests of epithelioid cells. We
      concluded that MAJM on a hyperpigmented macule is the subtype of the nevus
      spilus.

PMID- 8277042
TI  - A combination of speckled lentiginous nevus with patch-type blue nevus.
AB  - A peculiar case of "nevus on nevus" was reported. A 67-year-old man had had a
      pigmented lesion in the left hypochondrial area since birth. The
      clinicopathologic findings of the pigmented lesion revealed a combination of
      speckled lentiginous nevus and patch-type blue nevus. This case of "nevus on
      nevus" is not described under the term of combined nevus as is current in the
      literature; it was considered to be a subtype of the type II atypical blue nevus
      described by Kawamura.

PMID- 8277043
TI  - Progressive systemic sclerosis preceded by malignant lymphoma.
AB  - We report a patient who suffered from progressive systemic sclerosis (PSS) two
      years after she showed evidence of malignant lymphoma of the jejunum. Surgical
      resection of the tumor mass and VEMP regimen were successful; the patient was in
      remission but died of acute respiratory failure five years later. Although
      several reports have reported malignant lymphoma associated with PSS, lymphoma
      antecedent to PSS is rarely seen. Immune abnormalities including a high titer of
      antinuclear factor and positive anti-RNP antibodies were suspected to be
      associated with the development of PSS in our case.

PMID- 8277044
TI  - Joint pains with psoriasis and long-term systemic etretinate therapy: a case
      report and summary of 12 cases.
AB  - We report a case of psoriasis with joint pain related to long-term etretinate
      therapy. In addition, our experiences with twelve additional patients with
      psoriasis who also received etretinate therapy are discussed.

PMID- 8277045
TI  - An evaluation, using computerized image analysis, of antimicrobial efficacy of an
      automatic hand washing machine with ultrasonic wave spraying.
AB  - We studied the antimicrobial efficacy of hand washing with a quick-dry hand
      washing machine [TE-KIREIKI] employing ultrasonic wave spraying and its
      incidental alcohol-based product [AROKULIN-E]. The subjects of this study were 10
      males who had been instructed not to use any antimicrobial agent for the previous
      2 weeks or any hand soap for the previous 5 hours. They pressed their palms on
      agar before and after washing their hands. After 48-hour incubation at 37 degrees
      C, the bacterial colonies grown on the agar were counted using the [ASPECT] image
      processing system. The colony count was expressed as the post-stamp versus pre
      stamp percent (%) reduction. Two patterns of hand washing were examined in this
      study: [A] a 3-second hand wash using an alcohol-based product [AROKULIN-E] and
      [B] a 30-second hand wash using a nonmedicated detergent soap with running water
      in addition to hand washing by [A]. The percent (%) reduction after hand washing
      patterns [A] and [B] were 49.1% and 51.3%. These reduction rates indicated that
      these patterns did not eradicate bacteria from the hand surface. Therefore, we
      concluded that this quick-dry hand washing machine employing an ultrasonic wave
      spraying method combined with an alcohol-based product needs improvement.

PMID- 8277046
TI  - Intravascular papillary endothelial hyperplasia on the penis: report of a case.
AB  - An 82-year-old Japanese man with intravascular papillary endothelial hyperplasia
      on the penis is described. To the best of our knowledge, this is the first report
      of a patient who developed this tumor on his penis.

PMID- 8277047
TI  - Unusual widespread type of angiolymphoid hyperplasia with eosinophilia mimicking
      prurigo nodularis.

PMID- 8277048
TI  - Laser use debated.

PMID- 8277049
TI  - The pendulum has swung too far.

PMID- 8277050
TI  - Dentin bonding recognition.

PMID- 8277051
TI  - How to treat patients.

PMID- 8277052
TI  - Recognizing dental schools.

PMID- 8277053
TI  - Researchers develop mercury-free dental material.

PMID- 8277054
TI  - ADA Legal Affairs Division answers HIV questions.

PMID- 8277055
TI  - 'The best dentistry on earth.' Dr. James H. Gaines installed as ADA's 130th
      president.

PMID- 8277056
TI  - Digital radiology. Facts and fictions.
AB  - Dental digital radiology is a rapidly changing field. The advantages and
      disadvantages are presented with an understanding that attention to fundamentals
      is paramount. The message for the near future is cautious optimism.

PMID- 8277058
TI  - Rotary dental instruments and the potential risk of transmission of infection:
      herpes simplex virus.
AB  - A laboratory model of herpes simplex virus infection was used to assess the
      potential contamination of dental handpieces. When contaminated instruments were
      treated with surface disinfection and internal chemical disinfection, viable
      virus was eliminated in all instruments.

PMID- 8277057
TI  - Evaluating interfacial gaps for esthetic inlays.
AB  - Because of some inadequacies associated with the direct fill posterior composite
      resin, the inlay/onlay form of the same material or ceramic agents has been
      introduced. This clinical investigation measured the wear rate of several types
      of luting agents with both resin and ceramic restorative systems and identified
      several factors related to wear of the cementing agent.

PMID- 8277059
TI  - How cocaine abuse affects post-extraction bleeding.
AB  - The effects of cocaine and the relevance of cocaine abuse to clinical dentistry
      are discussed. Severe bleeding after an extraction is reported.

PMID- 8277060
TI  - When the bleeding won't stop: a case report on a patient with hemophilia.
AB  - A 39-year-old male developed severely prolonged bleeding after periodontal
      surgery because of a previously undetected clotting Factor XI deficiency
      (Hemophilia C). Diagnosis and treatment of this bleeding disorder are discussed.

PMID- 8277061
TI  - 1993 in review: a look back on a year of advancement.

PMID- 8277062
TI  - Periodontitis and tooth loss: comparing diabetics with the general population.
AB  - People with diabetes may be at increased risk for periodontal disease. This study
      compared the periodontal health of diabetic and employed adults. While tooth loss
      and gingival attachment was similar for both groups, diabetics had a greater
      prevalence and extent of periodontal pockets. Diabetics with poor metabolic
      control and calculus also had more periodontitis.

PMID- 8277063
TI  - How the new tax act affects practice sales.
AB  - The new tax act affecting rate changes also contains new rules for dealing with
      the intangible assets--including goodwill--involved in practice sales. A second
      concern is the permanent phaseout of some personal exemptions and certain
      itemized business deductions. There's still some good news.

PMID- 8277064
TI  - Tax act phases out exemptions, deductions.

PMID- 8277065
TI  - Reactions to latex in health care setting: dealing with patient/worker concerns.
      Council on Dental Materials, Instruments and Equipment; Council on Dental
      Therapeutics; Council on Dental Research.

PMID- 8277066
TI  - Halving of mortality at 1 year by domiciliary thrombolysis in the Grampian Region
      Early Anistreplase Trial (GREAT).
AB  - OBJECTIVES: Our aim was to determine the time saved by administration of
      thrombolytic therapy at home rather than in the hospital and to assess whether
      earlier thrombolysis resulted in decreased mortality from acute myocardial
      infarction. BACKGROUND: There is much theoretic, experimental and trial evidence
      to indicate that in acute myocardial infarction the earlier that thrombolytic
      therapy is given, the greater its efficacy. However, the clinical importance of
      this time effect is uncertain. METHODS: In a randomized double-blind parallel
      group clinical trial, 311 patients with suspected acute myocardial infarction
      seen by their general practitioners within 4 h of symptom onset were given
      intravenous anistreplase (30 U) either at home or later, after arrival in the
      hospital. RESULTS: Anistreplase was given at home or in the hospital at median
      times of 101 and 240 min, respectively, after symptom onset. The median time
      saved by domiciliary thrombolysis was 130 min. By the end of 1 year after trial
      entry, 17 (10.4%) of 163 patients given anistreplase at home died compared with
      32 (21.6%) of 148 in those allotted anistreplase in the hospital (relative
      reduction 52%, 95% confidence interval 14% to 89%, p = 0.007). CONCLUSIONS: In
      this trial the time saved by domiciliary thrombolysis by primary care physicians
      was > 2 h. It is likely that a similar time saving would be achieved if
      prehospital thrombolysis were to become established practice. Prehospital
      thrombolysis resulted in a halving of the mortality rate from acute myocardial
      infarction.

PMID- 8277067
TI  - New algorithm for the localization of accessory atrioventricular connections
      using a baseline electrocardiogram.
AB  - OBJECTIVES: In this study, we propose a new algorithm for accessory
      atrioventricular pathway localization using a 12-lead electrocardiogram (ECG).
      BACKGROUND: Radiofrequency catheter ablation produces a very discrete lesion, and
      ECG localization based on surgical dissection is obsolete. METHODS: Stepwise
      discriminant analysis was used to assess the relation of 18 pre-excited ECG (QRS
      duration > 100 ms) variables to the site of successful ablation in 93 patients.
      The most discriminating variables were combined to form rules for each location.
      The ECGs were retested by these rules to determine predictive accuracy. RESULTS:
      If the precordial QRS transition was at or before lead V1, the pathway had been
      ablated on the left side. If it was after lead V2, the pathway had been ablated
      on the right side. If the QRS transition was between leads V1 and V2 or at lead
      V2, then if the R wave amplitude in lead I was greater than the S wave by > or =
      1.0 mV, it was right-sided; otherwise, it was left-sided (p < 0.0001, sensitivity
      100%, specificity 97%). Right-side pathways. If the QRS transition was between
      leads V2 and V3, the pathway was right septal; if after lead V4, it was right
      lateral. If it was between leads V3 and V4, then if the delta wave amplitude in
      lead II was > or = 1.0 mV, it was right septal; otherwise, it was right lateral
      (p < 0.0001, sensitivity 97%, specificity 95%). In right lateral locations, if
      the delta wave frontal axis was > or = 0 degrees, or if it was < 0 degrees but
      the R wave amplitude in lead III was > or = 0 mV, it was anterolateral;
      otherwise, it was posterolateral (p < 0.0001, sensitivity 100%, specificity
      87.3%). Anteroseptal pathways had a sum of delta wave polarities in leads II, III
      and aVF > or = +2(p < 0.0001, sensitivity 100%, specificity 100%). Posteroseptal
      pathways (inferior delta wave sum < or = -2) were less well discriminated from
      right midseptal pathways (inferior delta wave sum < or = 1 > or = -1) (p <
      0.0001, sensitivity 76.5%, specificity 71%) [corrected]. Left-sided pathways. Two
      or more positive delta waves in the inferior leads or the presence of an S wave
      amplitude in lead aVL greater than the R wave, or both, discriminated left
      anterolateral pathways from posterior pathways (p < 0.001, sensitivity and
      specificity 100%). If the R wave in lead I was greater than the S wave by > or =
      0.8 mV, and the sum of inferior delta wave polarities was negative, the location
      was posteroseptal; otherwise, it was posterolateral (p < 0.05, sensitivity 71.4%,
      specificity 100%). CONCLUSIONS: Using the algorithm derived, a right-sided
      accessory pathway can be reliably distinguished from one that is left-sided,
      right free wall from right septal, right anterolateral from posterolateral and
      anteroseptal from other right septal pathways. Left anterolateral pathways can be
      distinguished from left posterior pathways and left posterolateral pathways from
      left posteroseptal pathways.

PMID- 8277068
TI  - A randomized trial of intravenous heparin in conjunction with anistreplase
      (anisoylated plasminogen streptokinase activator complex) in acute myocardial
      infarction: the Duke University Clinical Cardiology Study (DUCCS) 1.
AB  - OBJECTIVES: We designed a randomized trial to evaluate the effects of heparin
      administration in conjunction with anistreplase (anisoylated plasminogen
      streptokinase activator complex [APSAC]) on arterial patency and clinical end
      points. BACKGROUND: The role of conjunctive intravenous heparin therapy with
      APSAC has not been tested despite the recommendations that intravenous heparin
      should be used. METHODS: Four hours after APSAC administration, 250 patients with
      acute myocardial infarction were randomly assigned to receive 325 mg of either
      aspirin alone or aspirin and a continuous infusion of heparin (15 IU/kg body
      weight per h). Clinical ischemic events and bleeding complications were
      monitored. On hospital day 5, coronary arteriography and left ventriculography
      were performed. RESULTS: The primary end point of the trial (the combined outcome
      of death, reinfarction, recurrent ischemia and occlusion of the infarct-related
      artery) occurred in 42% of the heparin-treated group versus 43% of the group
      treated without heparin (p = 0.94). A patent infarct-related artery was present
      in 80% of the patients treated with heparin and in 73% of those treated without
      heparin (p = 0.26). Left ventricular function, as measured by ejection fraction,
      was well preserved in both groups (52% vs. 50.5%, respectively, p = 0.29). The
      overall bleeding rate was higher in patients with (32%) than without (17.2%)
      heparin (p = 0.006). CONCLUSIONS: Weight-adjusted intravenous heparin therapy
      after APSAC in acute myocardial infarction does not reduce the combined incidence
      of death, reinfarction, recurrent ischemia and occlusion of the infarct-related
      artery. Furthermore, withholding intravenous heparin therapy is associated with a
      46% reduction in bleeding complications. Our findings do not support the addition
      of intravenous heparin after APSAC therapy, as currently recommended, and suggest
      that a strategy of withholding heparin is simpler and safer and does not place
      the patient at increased risk for ischemic complications after myocardial
      infarction.

PMID- 8277069
TI  - Analysis of the initiation of spontaneous monomorphic ventricular tachycardia by
      stored intracardiac electrograms.
AB  - OBJECTIVES: This study was designed to analyze stored intracardiac electrograms
      generated during spontaneous monomorphic ventricular tachycardia to examine the
      possible mechanisms responsible for the initiation of ventricular tachycardia in
      a group of postinfarction patients. BACKGROUND: Implantable cardioverter
      defibrillators capable of storing electrograms during an arrhythmic event provide
      an intracardiac electrogram analog to Holter ambulatory electrocardiographic
      monitoring. Such electrograms are of value in arrhythmia diagnosis and in
      determining the appropriateness of implantable cardioverter-defibrillator therapy
      and may aid in understanding the initiation of ventricular arrhythmias. METHODS:
      We studied 73 stored electrograms in 22 postinfarction patients with spontaneous
      monomorphic ventricular tachycardia. Premature depolarizations before tachycardia
      were classified by morphology and number. Electrogram morphology was compared
      with the morphology of the baseline rhythm and ventricular tachycardia.
      Prematurity was assessed by the coupling interval and a calculated prematurity
      ratio. RESULTS: During baseline rhythm, ectopic activity was present in 30 (41%)
      of 73 stored episodes. Ventricular tachycardia was preceded by a short-long-short
      sequence in 14% of episodes and by a rapid ventricular rhythm in 5.5% of
      episodes. The onset of ventricular tachycardia was marked by single premature
      depolarizations in 33 episodes (45%), by pairs in 16 (22%) and by multiple
      complexes in 24 (33%). Morphology was similar to that of the ensuing tachycardia
      in 35 episodes (48%). The mean coupling interval was 364 ms, and the mean
      prematurity ratio was 0.56. In all 10 episodes (14%) where the prematurity ratio
      was < 0.40, a short-long-short sequence was responsible. When classified by
      morphology, the mean prematurity ratio of depolarizations dissimilar to
      ventricular tachycardia (0.53) was significantly less than that of the
      morphologically similar group (0.60, p = 0.035). CONCLUSIONS: In this select
      group of postinfarction patients with recurrent sustained monomorphic ventricular
      tachycardia treated with implantable cardioverter-defibrillators, ventricular
      tachycardia was most often preceded by late-coupled premature depolarizations.
      Not infrequently, a short-long-short sequence occurred before tachycardia.
      Premature depolarizations with a morphology different from that of the
      tachycardia occurred earlier in the cardiac cycle than did those with a
      morphology similar to that of the tachycardia. These findings may reflect
      different mechanisms of ventricular tachycardia initiation.

PMID- 8277070
TI  - Sensing/pacing lead complications with a newer generation implantable
      cardioverter-defibrillator: worldwide experience from the Guardian ATP 4210
      clinical trial.
AB  - OBJECTIVES: This report describes the sensing/pacing lead complications that
      developed during a worldwide clinical trial of a new implantable cardioverter
      defibrillator. BACKGROUND: The reliability of the leads used for sensing and
      pacing with the implantable cardioverter-defibrillator has not been adequately
      studied. METHODS: The Guardian ATP 4210 was implanted in 302 patients. The
      sensing/pacing leads consisted of either two unipolar epicardial electrodes or a
      bipolar endocardial electrode from a variety of manufacturers. RESULTS: During a
      mean follow-up period of 380 days, 39 patients (12.9%) required reoperation
      because their device developed sensing/pacing lead system complications. The most
      common clinical presentation was device oversensing (multiple tachycardia or
      noise detections or inappropriate shocks), which was observed in 27 patients,
      whereas elevated pacing thresholds were seen in 10 patients. Forty-one (11.8%) of
      347 implanted lead systems required revision. The mean time to revision was 156
      +/- 145 days. Actuarial lead survival rate at 1 and 3 years was 89% and 79%,
      respectively. Epicardial lead systems required significantly (p < 0.05) more
      revision than did endocardial systems, but when adapter problems were excluded,
      the revision rates of epicardial and endocardial leads were similar. Causes of
      lead system failures included adapter connection problems, lead dislodgement and
      insulation disruption. Predictors of lead revision were use of an epicardial lead
      system or an adapter. CONCLUSIONS: A high rate of sensing/pacing lead
      complications was found with this newer generation implantable cardioverter
      defibrillator. The enhanced diagnostic and data storage capabilities of this
      implantable cardioverter-defibrillator facilitated the recognition and
      troubleshooting of these complications. These findings emphasize the need for
      careful surveillance and testing of implantable cardioverter-defibrillator
      sensing/pacing leads during follow-up.

PMID- 8277071
TI  - Electrocardiographic diagnosis of left ventricular hypertrophy by the time
      voltage integral of the QRS complex.
AB  - OBJECTIVES: This study was conducted to test the hypothesis that the time-voltage
      integral of the QRS complex can improve the electrocardiographic (ECG)
      identification of left ventricular hypertrophy. BACKGROUND: Standard ECG criteria
      have exhibited poor sensitivity for left ventricular hypertrophy at acceptable
      levels of specificity. However, left ventricular mass may be more closely related
      to the time-voltage integral of the summed left ventricular dipole than to QRS
      duration or voltages used in standard ECG criteria. METHODS: Standard 12-lead
      ECGs, orthogonal lead signal-averaged ECGs and echocardiograms were obtained in
      62 male control subjects without left ventricular hypertrophy and 51 men with
      left ventricular hypertrophy defined by echocardiographic criteria (indexed left
      ventricular mass > 125 g/m2). Voltage of the QRS complex was integrated over the
      total QRS duration in leads X, Y and Z to calculate the time-voltage integral of
      each orthogonal lead, of the maximal spatial vector complex and of the
      horizontal, frontal and sagittal plane vector complexes. RESULTS: At matched
      specificity of 99%, the 73% (37 of 51) sensitivity of the time-voltage integral
      of the vector QRS complex in the horizontal plane was significantly greater than
      the 10% sensitivity of the Romhilt-Estes point score, the 16% sensitivity of QRS
      duration alone, the 22% sensitivity of Cornell voltage, the 33% sensitivity of
      the 12-lead sum of QRS voltage and the 37% sensitivity of Sokolow-Lyon voltage
      (each p < 0.001). Sensitivity of the horizontal plane time-voltage integral was
      also greater than the 10% to 51% sensitivity of the time-voltage integral
      calculated in the individual X, Y or Z leads (p < 0.01 to < 0.001), the 18% and
      35% sensitivity of the time-voltage integrals of the frontal and sagittal plane
      vectors (p < 0.001) and the 49% sensitivity of the time-voltage integral of the
      maximal spatial vector complex calculated from all three orthogonal leads (p <
      0.001). Comparison of receiver operating characteristic curves confirmed that the
      superior performance of the horizontal plane time-voltage integral relative to
      standard and other signal-averaged criteria was independent of partition value
      selection. CONCLUSIONS: These findings suggest that use of the time-voltage
      integral of the QRS complex, a method that can be readily implemented on
      commercially available computerized ECG systems, can improve the accuracy of ECG
      methods for the identification of left ventricular hypertrophy.

PMID- 8277072
TI  - Validation of global and segmental left ventricular contractile function using
      gated planar technetium-99m sestamibi myocardial perfusion imaging.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that segmental
      wall motion analysis determined from gated planar technetium-99m sestamibi
      myocardial imaging is reproducible and agrees well with echocardiographic data.
      BACKGROUND: Technetium-99m sestamibi is a new radiopharmaceutical recently
      approved for myocardial perfusion imaging. Its advantages include a dosimetry
      that allows use of a dose 10 to 15 times higher than that of thallium-201. As a
      result, myocardial counts are markedly improved and images can be collected in a
      gated mode to potentially allow assessment of global and segmental ventricular
      function. However, the reproducibility and accuracy of technetium-99m sestamibi
      imaging for measurement of global and segmental left ventricular function have
      not been evaluated or compared with those of a standard ventricular function
      technique, such as echocardiography. METHODS: We studied 136 patients referred
      for clinical technetium-99m sestamibi imaging. One-day rest-stress planar
      technetium-99m sestamibi protocols were used, gating the stress images. After
      technetium-99m sestamibi imaging, all patients had standard rest two-dimensional
      echocardiography. Global and segmental technetium-99m sestamibi and
      echocardiographic left ventricular contraction was graded qualitatively as normal
      or abnormal using a four-point grading system. RESULTS: Interobserver and
      intraobserver agreement was extremely high for global and segmental technetium
      99m sestamibi wall motion analysis, with absolute agreements ranging from 0.92 to
      1.00 and corresponding kappa values of 0.74 to 1.00 (p < 0.00001). Agreement with
      global and segmental echocardiographic wall motion was similarly very high, with
      absolute agreements ranging from 0.93 to 1.00 and corresponding kappa values of
      0.75 to 1.00 (p < 0.00001). CONCLUSIONS: Gated technetium-99m sestamibi cardiac
      imaging provides information with regard to rest global and segmental left
      ventricular systolic function that is highly reproducible and agrees very well
      with results of two-dimensional echocardiography.

PMID- 8277073
TI  - Autoantibodies against human ventricular myosin in sera of patients with acute
      and chronic myocarditis.
AB  - OBJECTIVES: The present study investigated the presence of antimyosin
      autoantibodies in sera of patients with myocarditis and in three control groups:
      healthy blood donors, patients with alcoholic cardiomyopathy and patients with
      other cardiac diseases. BACKGROUND: An increasing body of evidence indicates that
      in the course of myocarditis, autoimmunologic mechanisms may play a pathogenetic
      role. Animal studies with Coxsackie B3 virus-induced murine myocarditis could
      demonstrate the appearance of circulating autoantibodies against cardiac myosin.
      METHODS: Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) and
      Western blot with human left ventricular myosin as antigen. RESULTS: Seventeen
      (42%) of 40 serum samples from patients with myocarditis showed antibody-binding
      against myosin, whereas only 1 (2.5%) of 39 samples from healthy blood donors and
      9 (21%) of 43 samples from patients with other cardiac diseases showed
      autoantibodies against myosin (p < 0.05 vs. myocarditis). In sera from patients
      with alcoholic cardiomyopathy (n = 12), no antibodies against human ventricular
      myosin could be detected. In Western blots, the antimyosin antibodies in patients
      with myocarditis bound to the myosin heavy chain. Using protein-A sepharose
      chromatography, it could be shown that the antimyosin autoantibodies are of the
      immunoglobulin G (IgG) type. In ELISA, the antimyosin autoantibodies bind equally
      to myosin prepared from either cardiac or skeletal muscle, respectively.
      CONCLUSIONS: These results demonstrate the presence of autoantibodies against
      human ventricular myosin in patients with myocarditis. The prevalence of these
      autoantibodies is significantly higher in patients with myocarditis than in
      patients with other cardiac diseases. No organ specificity of the autoantibodies
      could be detected.

PMID- 8277074
TI  - Diagnostic role of Doppler echocardiography in constrictive pericarditis.
AB  - OBJECTIVES: This study was conducted to assess the diagnostic role of Doppler
      echocardiography in constrictive pericarditis. BACKGROUND: It has been observed
      that patients with constrictive pericarditis have a characteristic Doppler
      pattern of respiratory variation in ventricular filling and central venous flow
      velocities. However, the observation was based on a small number of patients with
      known diagnosis. METHODS: We reviewed the echocardiographic features of 28
      patients (21 men and 7 women; mean age +/- SD 55 +/- 15 years) with suspected
      constrictive pericarditis who underwent exploratory thoracotomy or
      pericardiectomy. RESULTS: At operation, constrictive pericarditis was diagnosed
      in 25 patients, restriction in 1 and normal pericardium in 2. Of the 25 patients
      with constriction, correct preoperative Doppler diagnosis was made in 22 (88%)
      and Doppler echocardiography showed restriction in 3. In two patients with a
      normal pericardium, Doppler features were consistent with constriction in one
      patient and were normal in the other. In the one patient with restriction,
      Doppler echocardiography showed restriction. In 19 patients with surgically
      proved constriction, repeat Doppler study after pericardiectomy showed normal
      findings in 14 and restriction in 5. Twelve of the 14 patients with normalized
      Doppler findings became asymptomatic, whereas all 5 with restrictive Doppler
      features remained symptomatic. CONCLUSIONS: Doppler echocardiography performed
      simultaneously with respiratory recording is highly sensitive for diagnosing
      constrictive pericarditis, and it appears to predict functional response to
      pericardiectomy.

PMID- 8277075
TI  - Altered peripheral vasodilator profile of nitroglycerin during long-term infusion
      of N-acetylcysteine.
AB  - OBJECTIVES: The aim of this study was to compare the short- and long-term effects
      of intravenous nitroglycerin plus placebo and nitroglycerin plus N-acetylcysteine
      on peripheral arteries, veins and microcirculation in humans. BACKGROUND: The
      thiol donor N-acetylcysteine may potentiate the hemodynamic response to nitrates
      in nitrate-tolerant and nontolerant patients. The vascular changes responsible
      for this effect are not clear. METHODS: Eight male volunteers were treated with
      nitroglycerin (0.1 microgram/kg per min) combined with N-acetylcysteine (2 g
      intravenously, followed by 5 mg/kg per h) or placebo for 23 h in a double-blind,
      randomized, crossover study. Venous volume, the diameter of the radial and
      temporal arteries, calf blood flow and subcutaneous blood flow were measured at
      baseline and repeated after 1 and 23 h of infusion. RESULTS: Prolonged
      coadministration of N-acetylcysteine and nitroglycerin potentiated the acute
      venodilator effect of nitroglycerin as estimated by changes in venous volume
      (nitroglycerin plus N-acetylcysteine, 4.45 +/- 0.36 ml/100 g; nitroglycerin plus
      placebo, 3.65 +/- 0.46 ml/100 g, mean +/- SEM, p < 0.05) and prevented
      development of tolerance as seen after 23 h of treatment with nitroglycerin plus
      placebo (4.35 +/- 0.25 vs. 3.47 +/- 0.41 ml/100 g, p < 0.05). N-acetylcysteine
      had no effect on nitroglycerin-induced changes in arterial diameters (p > 0.05)
      but significantly increased microcirculatory subcutaneous blood flow after 1 h
      (nitroglycerin plus N-acetylcysteine: 6.3 +/- 1.3 ml/100 g per min vs.
      nitroglycerin plus placebo: 3.5 +/- 0.3 ml/100 g per min, p < 0.05) and after 23
      h (4.4 +/- 0.6 vs. 3.1 +/- 0.5 ml/100 g per min, p < 0.05). CONCLUSIONS: The
      results suggest that coadministration of nitroglycerin and N-acetylcysteine in
      humans 1) potentiates and preserves nitroglycerin-induced venodilation and 2)
      augments the effect of nitroglycerin on small resistance vessels (regulating
      subcutaneous blood flow) without affecting the response to nitroglycerin in
      middle-sized arteries. Both the development of nitrate tolerance and the
      administration of N-acetylcysteine significantly change the normal vasodilator
      profile of nitroglycerin in humans.

PMID- 8277076
TI  - Ebstein's anomaly: presentation and outcome from fetus to adult.
AB  - OBJECTIVES: This study was conducted to investigate the presentation and outcome
      of patients with Ebstein's anomaly of the tricuspid valve. BACKGROUND: Ebstin's
      anomaly may present at any age and has a highly variable clinical course.
      Previous natural history studies have been based on clinical and angiographic
      diagnosis and have included mainly older children and adults. Echocardiography,
      however, has facilitated fetal and neonatal diagnosis so that the natural history
      needs to be redefined. METHODS: We reviewed 220 cases of Ebstein's anomaly
      presenting from fetal to adult life between 1958 and 1991, with 1 to 34 years of
      follow-up. RESULTS: The most common presentation in each age group was abnormal
      routine prenatal scan for fetuses (86%), cyanosis for neonates (74%), heart
      failure for infants (43%), incidental murmur for children (63%) and arrhythmia
      for adolescents and adults (42%). Early presentation was frequently associated
      with other cardiac lesions, usually pulmonary stenosis or atresia. Surgery was
      undertaken at some stage in 86 (39%) of the 220 patients. Actuarial survival for
      all liveborn patients was 67% at 1 year and 59% at 10 years. There were 58
      deaths, including 26 from heart failure, 19 perioperative and 8 sudden.
      Predictors of death included echocardiographic grade of severity at presentation
      (relative risk 2.7 for each increase in grade, 95% confidence limits 1.6 to 4.6),
      fetal presentation (6.9, confidence limits 1.6 to 16.5) and right ventricular
      outflow tract obstruction (2.1, confidence limits 1.1 to 4.4). Morbidity was
      mainly related to arrhythmias and late hemodynamic deterioration. Of 155
      survivors, 129 (83%) were in functional class 1 and 104 (67%) were receiving no
      medical therapy. CONCLUSIONS: In Ebstein's anomaly, fetal and neonatal
      presentation is associated with a poor outcome and can be predicted by the
      echocardiographic appearance and presence of associated lesions. In older
      children and adults, incidental findings and arrhythmia are common and the long
      term outcome is superior.

PMID- 8277077
TI  - Magnetic resonance imaging of heterotaxia in infants.
AB  - OBJECTIVES: This study assessed the usefulness and safety of magnetic resonance
      imaging (MRI) for systematically diagnosing heterotaxia in infants. BACKGROUND:
      Although it is important to diagnose and treat infants with heterotaxia, which is
      associated with viscerobronchial cardiovascular anomalies, systematic diagnosis
      of these anomalies by a single imaging technique is difficult. METHODS: Twenty
      patients with heterotaxia were evaluated. The infants ranged in age from 21 days
      to 12 months (average 5.2 months, average body weight 4.3 kg).
      Electrocardiographically gated MRI was performed by spin echo imaging techniques
      operating at 0.5 tesla. RESULTS: In all 20 patients, MRI results were sufficient
      to evaluate these anomalies without serious complications. In 17 patients,
      neither a spleen nor splenules were detected, but in 3 patients, a polymorphous
      spleen was visualized. In all 20 patients, bronchial anatomies were clearly
      visualized (bilateral eparterial bronchi in 14 patients, bilateral hyparterial
      bronchi in 2 and normal bronchial patterns in 4). Additionally, in a comparison
      of 149 observations of cardiovascular anatomy by MRI with those by angiography,
      discrepancies were found in only 10 observations (6.7%). CONCLUSIONS: Magnetic
      resonance imaging was found to be safe and very useful for the systematic
      diagnosis of heterotaxia in infants.

PMID- 8277078
TI  - Improved Doppler signal intensity in coronary arteries after intravenous
      peripheral injection of a lung-crossing contrast agent (SHU 508A)
AB  - OBJECTIVES: We tested the hypothesis that SHU 508A, a new lung-crossing contrast
      agent capable of increasing the Doppler signal to noise ratio in the right heart
      as well as left heart cavities after intravenous injection, could increase
      Doppler signal intensity in coronary arteries, thus improving the feasibility and
      quality of transesophageal Doppler echocardiographic evaluation of coronary blood
      flow velocity. BACKGROUND: Coronary blood flow velocity can be evaluated by
      transesophageal Doppler echocardiography. However, an adequate Doppler tracing is
      obtainable in a relatively low percent of patients. METHODS: Transesophageal
      Doppler echocardiography of coronary arteries was performed in 35 patients before
      and after SHU 508A injection at four different dosages (200 mg/ml in 5 ml, 200
      mg/ml in 10 ml, 300 mg/ml in 5 ml and 300 mg/ml in 10 ml). Color Doppler mapping
      of coronary flow and pulsed wave Doppler measurement of coronary blood flow
      velocity were attempted in all patients. RESULTS: Color Doppler flow mapping of
      105 evaluated coronary segments (left main, left anterior descending and
      circumflex in 35 patients) was not detectable or was weak in 88% of patients
      before and 33% of patients after echo contrast injection (p < 0.0001); it was
      optimal (that is, well delineated with complete flow mapping of the explored
      vessel) in only 11% of patients before and 67% after echo contrast injection (p <
      0.0001). In addition, pulsed wave Doppler signal quality improved after echo
      contrast injection: Pulsed wave Doppler recording of coronary blood flow velocity
      was not obtainable or was weak in 78% of cases before and 34% after echo contrast
      injection (p < 0.0001); pulsed wave Doppler recording of coronary blood flow
      velocity was optimal (that is, there was a complete and well defined outline of
      diastolic coronary blood flow velocity in 23% of cases before and 66% after echo
      contrast injection [p < 0.0001]. Both length and width of color Doppler mapping
      in the left anterior descending coronary artery increased after SHU 508A
      injection (from 5.75 +/- 5.32 and 1.51 +/- 1.17 to 17.04 +/- 8.76 and 4.21 +/-
      1.78 mm, respectively, mean +/- SD, p < 0.0001). CONCLUSIONS: The feasibility and
      quality of recording coronary blood flow velocity by transesophageal Doppler
      echocardiography are considerably improved by intravenous injection of SHU 508A.
      The improved feasibility of this new semi-invasive method for evaluating coronary
      blood flow velocity and flow reserve can considerably increase its research and
      clinical utilization.

PMID- 8277079
TI  - Effect of thrombolysis on heart rate variability and life-threatening ventricular
      arrhythmias in survivors of acute myocardial infarction.
AB  - OBJECTIVES: The aim of the present study was to determine the influence of early
      thrombolysis on ventricular tachyarrhythmias (clinical and inducible) and heart
      rate variability in survivors of myocardial infarction at high risk for life
      threatening ventricular arrhythmias. BACKGROUND: A greater electrical heart
      stability may be important in improving survival in patients treated with
      thrombolysis. Few data are available about the influence of fibrinolysis on
      postinfarction arrhythmic events and other prognostic variables, such as
      inducible ventricular tachycardia and heart rate variability. METHODS: The study
      group comprised 51 consecutive patients who underwent electrophysiologic study
      within 30 days of infarction, owing to the presence of two or more of the
      following criteria: left ventricular ejection fraction < 40%, late potentials and
      repetitive ventricular ectopic beats. Thirty patients underwent thrombolysis
      within 6 h of the onset of symptoms (Group A), and 21 received conventional
      treatment (Group B). Inducibility of sustained monomorphic ventricular
      tachycardia was tested in both groups, and the standard deviation of all normal
      RR intervals during 24-h Holter monitoring was calculated. All patients were
      prospectively evaluated for occurrence of arrhythmic events. RESULTS: The two
      groups were similar with regard to left ventricular ejection fraction (mean +/- 1
      SD 38 +/- 6% [Group A] vs. 36 +/- 8% [Group B]). Ventricular tachycardia was
      induced in 6 (20%) of 30 Group A patients versus 14 (67%) of 21 Group B patients
      (p = 0.002). The standard deviation of normal RR intervals was higher in Group A
      than in Group B (113 +/- 36 vs. 90 +/- 39 ms, p = 0.05). In patients with
      anterior infarction, the standard deviation of normal RR intervals was higher in
      19 patients with thrombolysis than in 16 patients with conventional treatment
      (118 +/- 41 vs. 74 +/- 24 ms, p = 0.0002). During a mean follow-up period of 23
      +/- 11 months, 4 (13%) of 30 Group A patients had an arrhythmic event versus 9
      (43%) of 21 Group B patients (p = 0.04). CONCLUSIONS: After myocardial
      infarction, in high risk patients, thrombolysis significantly reduced the
      occurrence of arrhythmic events independently of left ventricular function. This
      effect may be related to both an improvement in electrical heart stability, as
      elucidated by electrophysiologic study, and a favorable action on the cardiac
      sympathovagal balance.

PMID- 8277080
TI  - Coronary flow by transesophageal Doppler echocardiography: do saccharide-based
      contrast agents sweeten the pot?

PMID- 8277081
TI  - Short-term effects of naloxone on hemodynamics and baroreflex function in
      conscious dogs with pacing-induced congestive heart failure.
AB  - OBJECTIVES: The purpose of this study was to determine the effects of naloxone on
      systemic hemodynamics and reflex function in dogs with congestive heart failure
      induced by rapid pacing. BACKGROUND: We have shown previously that naloxone, an
      opiate receptor antagonist, improves cardiac output, aortic blood pressure,
      systolic performance and the baroreflex function in conscious dogs with chronic
      right-sided congestive heart failure. However, whether endogenous opioids also
      play a role n mediating the reduction of myocardial and baroreflex function in
      animals with left heart failure remains controversial. METHODS: We administered
      naloxone (1 mg/kg body weight) and normal saline solution to 15 dogs with pacing
      induced congestive heart failure (225 beats/min for 8 weeks) and 11 control dogs.
      In addition to systemic hemodynamic measurements, the slope of pressure-area
      relation obtained from echocardiography with intravenous bolus injection of
      phenylephrine was taken as a load-independent index of myocardial contractility.
      Baroreflex function was estimated by the slope of the regression line relating
      systolic aortic pressure and RR interval. RESULTS: Plasma beta-endorphin levels
      were elevated in dogs with congestive heart failure. Naloxone administration
      increased heart rate, mean aortic pressure, first derivative of left ventricular
      pressure, cardiac output and myocardial contractility in pacing-induced
      congestive heart failure. These changes correlated significantly with basal
      plasma beta-endorphin levels and were accompanied by increases in plasma beta
      endorphin and catecholamines after naloxone administration. However, unlike the
      hemodynamic and cardiac effects of naloxone, baroreflex function did not change
      after naloxone in dogs with congestive heart failure. CONCLUSIONS: The increase
      in basal plasma beta-endorphin suggests that the endogenous opiate system is
      activated in left-sided congestive heart failure. Because naloxone improves the
      systemic hemodynamics and myocardial contractile function under this condition,
      the endogenous opioids appear to play an important role in mediating the
      myocardial depression that occurs in heart failure. However, the endogenous
      opiate system has no apparent effect on the regulation of baroreflex control in
      heart failure induced by rapid pacing.

PMID- 8277082
TI  - Three-dimensional reconstruction of ventricular septal defects: validation
      studies and in vivo feasibility.
AB  - OBJECTIVES: The purpose of this study was to demonstrate the feasibility of in
      vivo three-dimensional reconstruction of ventricular septal defects and to
      validate its quantitative accuracy for defect localization in excised hearts
      (used to permit comparison of three-dimensional and direct measurements without
      cardiac contraction). BACKGROUND: Appreciating the three-dimensional spatial
      relations of ventricular septal defects could be useful in planning surgical and
      catheter approaches. Currently, however, echocardiography provides only two
      dimensional views, requiring mental integration. A recently developed system
      automatically combines two-dimensional echocardiographic images with their
      spatial locations to produce a three-dimensional construct. METHODS: Surgically
      created ventricular septal defects of varying size and location were imaged and
      reconstructed, along with the left and right ventricles, in the beating heart of
      six dogs to demonstrate the in vivo feasibility of producing a coherent image of
      the defect that portrays its relation to surrounding structures. Two additional
      gel-filled excised hearts with defects were completely reconstructed.
      Quantitative localization of the defects relative to other structures
      (ventricular apexes and valve insertions) was then validated for seven defects in
      excised hearts. The right septal margins of the exposed defects were also traced
      and compared with their reconstructed areas and circumferences. RESULTS: The
      three-dimensional images provided coherent images and correct spatial
      appreciation of the defects (two inlet, two trabecular, one outlet and one
      membranous Gerbode in vivo; one inlet and one apical in excised hearts). The
      distances between defects and other structures in the excised hearts agreed well
      with direct measures (y = 1.05x-0.18, r = 0.98, SEE = 0.30 cm), as did
      reconstructed areas (y = 1.0x-0.23, r = 0.98, SEE = 0.21 cm2) and circumferences
      (y = 0.97x + 0.13, r = 0.97, SEE = 0.3 cm). CONCLUSIONS: Three-dimensional
      reconstruction of ventricular septal defects can be achieved in the beating heart
      and provides an accurate appreciation of defect size and location that could be
      of value in planning interventions.

PMID- 8277083
TI  - Comparative efficacy of three indexes of left ventricular performance derived
      from pressure-volume loops in heart failure induced by tachypacing.
AB  - OBJECTIVES: The purpose of this study was to serially evaluate the response and
      variability of the end-systolic pressure-volume relation, the left ventricular
      end-diastolic volume-peak positive first derivative of left ventricular pressure
      (dP/dt) relation and the left ventricular end-diastolic volume-stroke work
      relation in the development of progressive left ventricular dysfunction.
      BACKGROUND: Evaluation of systolic performance of the failing left ventricle may
      be enhanced by using relatively load-insensitive measures of left ventricular
      performance. The end-systolic pressure-volume, left ventricular end-diastolic
      volume-peak positive dP/dt and left ventricular end-diastolic volume-stroke work
      relations adequately define left ventricular performance under multiple loading
      conditions, but efficacy has not been fully assessed in the failing heart,
      particularly in the intact circulation. METHODS: Fourteen dogs underwent
      instrumentation and rapid pacing to heart failure. Variably loaded pressure
      volume beats were produced by inferior vena cava occlusion. The dogs were
      evaluated at baseline and at three progressively more severe levels of left
      ventricular dysfunction. RESULTS: There was a progressive increase in left
      ventricular volumes at end-diastole ([mean value +/- SE] 60 +/- 28 to 73 +/- 29
      ml, p < 0.001) and end-systole (39 +/- 19 to 61 +/- 27 ml, p < 0.001) during the
      3 weeks of rapid pacing and a progressive decline in peak positive dP/dt (1,631
      +/- 410 to 993 +/- 222 mm Hg/s, p < 0.001) and ejection fraction (37 +/- 8% to 16
      +/- 11%, p < 0.001). There was a corresponding decline in the slope of each of
      the three relations: for end-systolic pressure-volume, 6.3 +/- 2.2 to 2.8 +/- 0.7
      (p < 0.05); for left ventricular end-diastolic volume-stroke work, 61.9 +/- 9.1
      to 26.5 +/- 2.4 (p < 0.05); and for left ventricular end-diastolic volume-peak
      positive dP/dt, 47.1 +/- 13.6 to 20.31 +/- 6.8 (p < 0.05). There was also a
      corresponding increase in position volumes: for end-systolic pressure-volume,
      33.6 +/- 3.9 to 61.2 +/- 6.6 ml (p < 0.05); for left ventricular end-diastolic
      volume-stroke work, 46.2 +/- 3.6 to 89.3 +/- 7.6 ml (p < 0.05); and for left
      ventricular end-diastolic volume-peak positive dP/dt, 29.1 +/- 19.1 to 68.6 +/-
      25.9 ml (p < 0.05). The relative degree of change in each of the three relations
      was similar as more severe heart failure developed. The coefficients of variation
      for position were significantly less than the variation for slopes. The response
      of volume intercepts was heterogeneous. For left ventricular end-diastolic volume
      stroke work, the intercept increased as ventricular performance decreased. The
      intercept of the end-systolic pressure-volume relation was significantly more
      variable than the left ventricular end-diastolic volume-stroke work relation and
      did not change with progressive heart failure. The intercept for left ventricular
      end-diastolic volume-peak positive dP/dt was highly variable and showed no
      consistent changes as left ventricular function declined. CONCLUSIONS: All three
      relations consistently describe changes in left ventricular performance brought
      about by tachypacing. Evolution of left ventricular dysfunction causes a decline
      in slope and a rightward shift of these relations. The position of the relation
      is the most sensitive and least variable indicator of left ventricular systolic
      performance.

PMID- 8277084
TI  - Severe exercise-induced ischemia does not identify high risk patients with normal
      left ventricular function and one- or two-vessel coronary artery disease.
AB  - OBJECTIVES: This study was conducted to determine whether severe exercise-induced
      ischemia identifies high risk patients with a normal left ventricular ejection
      fraction and one- or two-vessel coronary artery disease. BACKGROUND: Severe
      ischemia during exercise radionuclide angiography has been shown to identify high
      risk patients among certain other patient subsets. METHODS: Four hundred twenty
      patients with left ventricular ejection fraction > or = 50% and one- or two
      vessel disease underwent exercise radionuclide angiography within 3 months of
      coronary angiography. Patients were treated initially with revascularization (n =
      140) or medical therapy (n = 280) at the discretion of their physicians. Patients
      treated with revascularization were more likely to have angina by history, a
      positive exercise electrocardiogram, a lower exercise ejection fraction, two
      vessel disease and proximal left anterior descending coronary artery disease. Two
      hundred sixty-four of the 280 patients given medical therapy who had complete
      follow-up data formed the study group. Outcome was compared between patients with
      (n = 56) and without (n = 208) severe exercise-induced ischemia, defined by
      previously published criteria (work load < or = 600 kg-m/min, ST segment
      depression > or = 1 mm and decrease in ejection fraction with exercise). RESULTS:
      During follow-up, there were 30 initial cardiac events (12 cardiac deaths and 18
      nonfatal myocardial infarctions). There was no difference in the 5-year event
      free survival rate: 91% in patients with and 87% in patients without severe
      ischemia (p = 0.89). There was no association between event-free survival and
      severe ischemia (chi 2 = 1.41, p = 0.24). The study had approximately 80% power
      at alpha = 0.05 to detect a 25% decrease in event-free survival in the group with
      severe ischemia. In addition, there was no association between severe ischemia
      and outcome if late revascularization was included as an event or if the total
      mortality rate (overall survival) was analyzed. CONCLUSIONS: Severe exercise
      induced ischemia fails to identify a high risk subgroup among patients with
      normal left ventricular function and one- or two-vessel disease who are treated
      initially with medical therapy.

PMID- 8277085
TI  - Prognostic impact of myocardial ischemia.

PMID- 8277086
TI  - Does myocardial ischemia portend poor prognosis?

PMID- 8277087
TI  - Zatebradine, a specific bradycardic agent, enhances the positive inotropic
      actions of dobutamine in ischemic myocardium.
AB  - OBJECTIVES: This investigation determined whether attenuation of the tachycardia
      produced by dobutamine administration would improve perfusion and function distal
      to a severe coronary artery stenosis. BACKGROUND: Tachycardia adversely affects
      perfusion and function distal to a coronary artery stenosis. It is not known
      whether a specific bradycardic agent can improve blood flow and function in an
      ischemic zone during administration of dobutamine. METHODS: The effects of
      dobutamine (2, 5 and 10 micrograms/kg body weight per min) alone and in
      combination with zatebradine (0.5 mg/kg), a specific bradycardic agent, on
      hemodynamic status, segment shortening (ultrasound length transducers) and
      myocardial perfusion (microspheres) were studied in anesthetized dogs with severe
      left circumflex coronary artery stenosis. RESULTS: A 50% reduction in left
      circumflex coronary artery blood flow (58 +/- 4 to 29 +/- 2 ml/min [mean value +/
      SEM]) produced a decrease in systolic shortening in the ischemic zone. Only a
      dose of dobutamine that did not elevate heart rate (2 micrograms/kg per min)
      produced an increase in segment shortening in the ischemic zone. High doses of
      dobutamine (10 micrograms/kg per min) caused an increase in heart rate without
      improvement in function and a reduction in the subendocardial/subepicardial flow
      ratio (0.74 +/- 0.06 to 0.48 +/- 0.05). Zatebradine administered in the presence
      of dobutamine caused a decrease in heart rate, an increase in
      subendocardial/subepicardial blood flow ratio (0.48 +/- 0.05 to 0.78 +/- 0.09)
      and allowed an increase in ischemic zone segment shortening. When normalized for
      changes in heart rate, ischemic zone subendocardial flow increased by 123 +/- 41%
      (0.39 +/- 0.09 to 0.71 +/- 0.12 ml/100 g per beat). Atrial pacing abolished the
      effects of zatebradine. CONCLUSIONS: The present data suggest that the perfusion
      contraction matching that accompanies a decrease in heart rate results in
      enhancement of inotropic stimulation of an ischemic zone. The actions of
      zatebradine are related to an increase in subendocardial blood flow per beat that
      allows improvement of regional contractile function.

PMID- 8277088
TI  - Assessment of left ventricular performance by on-line pressure-area relations
      using echocardiographic automated border detection.
AB  - OBJECTIVES: The purpose of this study was to evaluate left ventricular
      performance by on-line pressure-area relations using echocardiographic automated
      border detection in the in situ canine heart in a manner similar to pressure
      volume analyses. BACKGROUND: Echocardiographic automated border detection can
      measure ventricular cavity area as an index of volume and may be interfaced with
      pressure to construct pressure-area loops on-line. METHODS: Eight anesthetized
      open chest dogs had simultaneous measurement of ventricular pressure, aortic flow
      and midventricular short-axis area. Pressure-area loops were constructed by a
      computer workstation interfaced with the ultrasound system. Stroke area (Maximal
      area--Minimal area) and stroke force (integral of P dA [P = pressure; A = area])
      values during inferior vena cava (n = 8) and aortic (n = 4) occlusions were
      compared with stroke volume and estimates of stroke work, respectively. Inotropic
      modulation was induced with dobutamine infusion (2 to 5 micrograms/kg body weight
      per min), followed by propranolol infusion (2 to 5 mg). End-systolic and maximal
      elastance and preload recruitable stroke force (stroke force versus end-diastolic
      area) were derived for each period. RESULTS: Changes in stroke area and stroke
      force were significantly correlated with changes in stroke volume and estimates
      of stroke work during caval occlusion (n = 8) (r = 0.87 +/- 0.02, SEE = 8 +/- 1%
      and r = 0.90 +/- 0.03, SEE = 8 +/- 2%, respectively). In dogs with aortic
      occlusion (n = 4), changes in stroke area significantly correlated with changes
      in stroke volume for pooled data (r = 0.84, SEE = 8%, y = 1.0x + 3). Ventricular
      performance increased with dobutamine infusion (n = 7): end-systolic elastance 30
      +/- 11 to 67 +/- 24 mm Hg/cm2 (p < 0.02 vs. control values); maximal elastance 37
      +/- 11 to 82 +/- 26 mm Hg/cm2 (p < 0.02 vs. control values); preload recruitable
      stroke force 81 +/- 24 to 197 +/- 92 mm Hg (p < 0.02 vs. control values).
      Decreases occurred with propranolol infusion (n = 5) end-systolic elastance 20 +/
      4 to 13 +/- 4 mm Hg/cm2 (p < 0.002 vs. control values); maximal elastance 29 +/-
      8 to 15 +/- 5 mm Hg/cm2 (p < 0.002 vs. control values); preload recruitable
      stroke force 66 +/- 14 to 40 +/- 9 mm Hg (p < 0.002 vs. control values).
      CONCLUSIONS: On-line pressure-area relations are a potentially useful means to
      assess left ventricular performance in a manner that is quantitatively similar to
      the predicted responses of pressure-volume relations.

PMID- 8277089
TI  - Effects of amiodarone on refractory ventricular fibrillation in acute myocardial
      infarction: experimental study.
AB  - OBJECTIVES: The aim of this study was to evaluate the efficacy of a single dose
      of intravenous amiodarone in facilitating defibrillation of ventricular
      fibrillation refractory to lidocaine and epinephrine plus direct current
      countershocks in experimental acute myocardial infarction. BACKGROUND: Amiodarone
      has been hailed as the most effective single antiarrhythmic drug for the
      treatment of ventricular arrhythmias. However, intravenous amiodarone has only
      sporadically been used in the defibrillation of ventricular fibrillation in acute
      myocardial infarction. METHODS: Acute myocardial infarction was induced in 60
      dogs by ligation of the proximal left anterior descending coronary artery for 2
      h. Animals that developed spontaneous ventricular fibrillation were treated with
      lidocaine and epinephrine plus five direct-current countershocks. Dogs with
      ventricular fibrillation refractory to this regimen were randomized to further
      treatment with additional intravenous administration of epinephrine and bolus
      lidocaine plus < or = 15 direct-current countershocks (group I) or administration
      of amiodarone, 10 mg/kg body weight intravenously, followed by defibrillation
      with direct-current counter-shock (group II). RESULTS: Sixteen (27%) of the 60
      dogs in which the protocol was attempted developed spontaneous ventricular
      fibrillation 21 min after ligation and were included in the study. Lidocaine and
      epinephrine plus five direct-current countershocks succeeded in converting
      ventricular fibrillation in one dog (6%). The other 15 dogs were randomized to
      group I (8 dogs) or group II (7 dogs). Defibrillation was achieved in one of the
      eight dogs in group I and in six of the seven dogs in group II (p < 0.005).
      CONCLUSIONS: In an experimental model of acute ischemia, intravenous amiodarone
      (10 mg/kg) influences positively the response to defibrillation of ventricular
      fibrillation refractory to lidocaine and epinephrine plus direct current
      countershocks.

PMID- 8277090
TI  - Clinical relevance of cardiac arrhythmias generated by afterdepolarizations. Role
      of M cells in the generation of U waves, triggered activity and torsade de
      pointes.
AB  - Recent findings point to an important heterogeneity in the electrical behavior of
      cells spanning the ventricular wall as well as important differences in the
      response of the various cell types to cardioactive drugs and pathophysiologic
      states. These observations have permitted a fine tuning and, in some cases, a
      reevaluation of basic concepts of arrhythmia mechanisms. This brief review
      examines the implications of some of these new findings within the scope of what
      is already known about early and delayed afterdepolarizations and triggered
      activity and discusses the possible relevance of these mechanisms to clinical
      arrhythmias.

PMID- 8277091
TI  - IPO-V2: a prospective, multicenter, randomized, comparative clinical
      investigation of the effects of sulodexide in preventing cardiovascular accidents
      in the first year after acute myocardial infarction.
AB  - OBJECTIVES: This study was conducted to assess the efficacy of sulodexide, a
      glycosaminoglycan compound with antithrombotic properties, in preventing death
      and thromboembolic events after acute myocardial infarction. BACKGROUND:
      Antithrombotic therapy has been found to play an important role in the prevention
      of cardiovascular events and death after acute myocardial infarction.
      Glycosaminoglycan-containing compounds, including sulodexide, show
      profibrinolytic and antithrombotic properties that render them suitable for use
      in patients after infarction. METHODS: A total of 3,986 patients who had
      recovered from acute myocardial infarction were randomized to receive either the
      standard therapy routinely administered at each study center, excluding
      antiplatelet and anticoagulant drugs (control group, 1,970 patients), or the
      standard therapy plus sulodexide (treated group, 2,016 patients). Between 7 and
      10 days after the episode of acute myocardial infarction, sulodexide was
      administered as a single daily 600-lipoprotein-lipase-releasing unit (LRU)
      intramuscular injection for the 1st month, followed by oral capsules of 500 LRU
      twice daily. Patients were evaluated for > or = 12 months. RESULTS: At the end of
      the study, 140 deaths (7.1%) were recorded in the control group and 97 (4.8%) in
      the sulodexide group (32% risk reduction, p = 0.0022, chi-square test). A total
      of 90 patients (4.6%) in the control group had a further infarction, compared
      with 66 (3.3%) in the sulodexide group (28% risk reduction, p = 0.035).
      Furthermore, a reduction in left ventricular thrombus formation (evaluated by
      echocardiography) was observed in the sulodexide group (n = 12; 0.6%), compared
      with values in the control group (n = 25; 1.3%) (53% risk reduction, p = 0.027).
      Sulodexide was well tolerated and devoid of significant adverse events. All
      significant results were confirmed by "actual treatment" analyses. CONCLUSIONS:
      The study provides evidence that long-term therapy with sulodexide started early
      after an episode of acute myocardial infarction is associated with reductions in
      total mortality, rate of reinfarction and mural thrombus formation.

PMID- 8277092
TI  - Disciplinary actions: how often and why?

PMID- 8277093
TI  - Similar results of percutaneous transluminal coronary angioplasty for women and
      men with postmyocardial infarction ischemia.
AB  - OBJECTIVES: The purpose of this study was to determine whether there are gender
      differences in the outcome of percutaneous transluminal coronary angioplasty
      performed for postmyocardial infarction ischemia. BACKGROUND: Although women have
      a higher mortality rate after myocardial infarction than that of men, they are
      less frequently referred for coronary angioplasty (and coronary artery bypass
      graft surgery) than are men, possibly because of expectations of a worse
      procedural outcome. METHODS: We analyzed the morbidity and mortality at coronary
      angioplasty and during a mean follow-up period of 34.4 months for women and 34.2
      months for men in 505 consecutive patients (164 women and 341 men) with
      postmyocardial infarction ischemia between 1981 and 1989. RESULTS: Compared with
      men, women had similar procedural success rates (89.6% and 91.2%, respectively),
      need for coronary artery bypass surgery (3.7% and 2.6%) and mortality rates at
      coronary angioplasty (0.6% and 0.9%). During the follow-up period, there were no
      significant gender differences in the requirement for coronary artery bypass
      surgery (3.6% and 4%), repeat angioplasty (18.7% and 17.3%), reinfarction (5.8%
      and 6%) and death (3.6% and 3.7%) or the combined end points of all four events
      (26.6% and 26.6%). Women had significantly more recurrent angina than did men
      (54% vs. 42.5%, p < 0.01), even though the extent of coronary artery disease and
      frequency of incomplete revascularization were similar in men and women.
      CONCLUSIONS: The procedural outcome of coronary angioplasty for postmyocardial
      infarction ischemia is similar in women and men. Long-term follow-up is also
      similar except that women experience an increased incidence of recurrent angina,
      an outcome also reported after bypass surgery. Therefore, concerns over the
      safety of coronary angioplasty in women should not adversely influence decisions
      concerning referral of women for coronary angioplasty after myocardial infarction
      complicated by ischemia.

PMID- 8277094
TI  - Qualitative and quantitative contrasts in the mechanisms of lumen enlargement by
      coronary balloon angioplasty and directional coronary atherectomy.
AB  - OBJECTIVES: This study was designed to define and contrast the mechanisms of
      lumen enlargement from coronary balloon angioplasty and directional coronary
      atherectomy using intracoronary ultrasound imaging in vivo. BACKGROUND: The
      mechanisms of lumen enlargement produced by percutaneous transluminal coronary
      balloon angioplasty and directional coronary atherectomy are not known because
      the coronary artery wall has not previously been studied both before and after
      dilation. METHODS: We used intracoronary ultrasound to quantitate coronary lumen,
      vessel and plaque area both before and immediately after successful coronary
      angioplasty (n = 30) and directional coronary atherectomy (n = 25) at the site of
      most severe stenosis. RESULTS: Angioplasty increased lumen area by 2.80 +/- 0.25
      mm2 (mean +/- SE, p < 0.0001). Eighty-one percent of this lumen gain resulted
      from an increase in vessel area and the remaining 19% from a reduction in plaque
      area. Lumen gain of individual lesions was separated into three groups: 67% had
      an increase in vessel area (vessel expansion), 13% had a decrease in plaque area
      and 20% had a combination of both. In contrast, vessel expansion contributed only
      22% of the lumen gain with directional coronary atherectomy, with the majority
      (78%) of increase in lumen size coming from a reduction in plaque area.
      Directional coronary atherectomy increased lumen area from 2.36 +/- 0.05 to 7.00
      +/- 0.28 mm2 (p < 0.0001). Plaque reduction was the sole mechanism in 60% of
      lesions, vessel expansion was the sole mechanism in 12% and a combination of both
      mechanisms occurred in 28%. Lumen enlargement of eccentric lesions treated with
      directional coronary atherectomy was more commonly associated with plaque
      reduction (p < 0.02), whereas eccentricity did not affect the mechanism of lumen
      enlargement with coronary angioplasty. CONCLUSIONS: This is the first study to
      systematically examine the coronary artery wall in vivo at the site of a severe
      stenosis both before and after catheter-based interventions in humans. Lumen
      enlargement from coronary angioplasty occurs predominantly from vessel expansion
      or stretching, although a reduction in plaque area contributes to the lumen gain
      in many patients and is the sole mechanism in a few. Lumen gain from directional
      coronary atherectomy is predominantly from reduction in plaque area (probably
      owing to tissue removal), although vessel stretching (balloon effect) occurs and
      is the sole mechanism in a small minority of vessels. Plaque reduction is more
      common in directional coronary atherectomy of eccentric lesions.

PMID- 8277095
TI  - Clinical, histologic and quantitative angiographic predictors of restenosis after
      directional coronary atherectomy: a multivariate analysis of the renarrowing
      process and late outcome.
AB  - OBJECTIVES: To characterize predictors of restenosis after successful directional
      atherectomy, we reviewed the clinical, angiographic and procedural data obtained
      during 132 consecutive procedures. METHODS: Clinical and angiographic follow-up
      data were obtained in a prospectively collected and consecutive series of 125
      patients who underwent 132 atherectomy procedures for de novo (89%) or restenotic
      (11%) lesions in native coronary arteries. Restenosis was assessed clinically and
      by quantitative coronary angiography. A dual approach to data analysis was taken
      to gain insight into factors affecting the clinical outcome and vessel wall
      healing response. Therefore, multivariate analysis was performed to 1) determine
      the correlates of residual lumen diameter at follow-up (angiographic outcome),
      and 2) characterize the determinants of the late lumen loss (renarrowing
      process). RESULTS: Clinical and angiographic follow-up data after successful
      atherectomy were obtained in 100% and 95%, respectively. Atherectomy achieved an
      acute lumen gain of 1.28 +/- 0.48 mm (mean +/- SD), resulting in a minimal lumen
      diameter of 2.44 +/- 0.47 mm. At follow-up, the minimal lumen diameter decreased
      to 1.78 +/- 0.64 mm. The angiographic restenosis rate was 28% if the traditional
      50% stenosis cutoff criterion was applied. Larger vessel size and postatherectomy
      minimal lumen diameter and right coronary or left circumflex artery lesions were
      independent predictors of a larger minimal lumen diameter (angiographic outcome).
      Lumen loss during follow-up (renarrowing process) was independently predicted by
      relative lumen gain and preprocedural minimal lumen diameter. CONCLUSIONS: In
      analyzing the long-term results of new interventional techniques such as
      directional atherectomy, the late lumen loss during follow-up (renarrowing
      process), which is characterized by the vessel wall healing response after an
      intervention, should be considered together with the residual lumen diameter at
      follow-up (clinical outcome). It is clear that whereas improved clinical outcome
      is associated with larger vessel size and postprocedural lumen diameter and non
      left anterior descending artery location, greater relative gain at intervention
      is predictive of more extensive lumen renarrowing.

PMID- 8277096
TI  - Proliferation and extracellular matrix synthesis of smooth muscle cells cultured
      from human coronary atherosclerotic and restenotic lesions.
AB  - OBJECTIVES: The purpose of this study was to examine the proliferative capacity
      and extracellular matrix synthesis of human coronary plaque cells in vitro.
      BACKGROUND: Common to both primary atherosclerosis and restenosis are vascular
      smooth muscle cell proliferation and production of extracellular matrix proteins.
      The applicability to humans of experimental animal models of these processes has
      been questioned. METHODS: Primary atherosclerotic and restenotic lesions were
      excised by percutaneous directional coronary atherectomy in 93 patients. Smooth
      muscle cells were cultivated by an explant technique and identified by their
      morphology in culture, ultrastructural features under electron microscopy and
      immunostaining using monoclonal antibodies to smooth muscle cell alpha-actin.
      Proliferation in secondary culture was assessed with growth curves and the
      synthesis of collagen and sulfated glycosaminoglycans by the incorporation of 3H
      proline and 35S-sulfate, respectively. These studies were also performed in cells
      derived from human umbilical artery media. RESULTS: Success rates for primary
      (45%) and secondary (12%) culture of coronary cells were not influenced by
      clinical variables or lesion category. Primary culture success was improved by
      the presence of organized thrombus in the plaque and in relation to increased
      maximal cell density of the atherectomy specimen. Restenotic cells displayed more
      rapid growth than did cells of primary atherosclerotic origin, which grew in a
      manner similar to that of umbilical artery cells. Mean calculated population
      doubling times for the three cell groups were 52 h (95% confidence interval [CI]
      48 to 58 h), 71 h (95% CI 62 to 83 h) and 74 h (95% CI 65 to 84 h), respectively.
      Restenotic and primary atherosclerotic cells did not differ in the synthesis of
      collagen ([mean +/- SEM] 0.034 +/- 0.004 vs. 0.033 +/- 0.004 nmol
      isotope.microgram protein-1, p = NS) or sulfated glycosaminoglycans (11.47 +/-
      1.07 vs. 15.37 +/- 3.10 nmol isotope.microgram protein-1, p = NS), but the
      coronary cells synthesized significantly more collagen and sulfated
      glycosaminoglycans than did umbilical artery cells (0.019 +/- 0.004 and 5.43 +/-
      1.00 nmol isotope.microgram protein-1, respectively, both p < 0.05). CONCLUSIONS:
      These data indicate that increased smooth muscle cell proliferation contributes
      to coronary restenosis in humans and support the concept that the extracellular
      matrix synthesis of adult smooth muscle cells is important to lesion formation.

PMID- 8277097
TI  - Efficacy of 100 mg of double-bolus alteplase in achieving complete perfusion in
      the treatment of acute myocardial infarction.
AB  - OBJECTIVES: The purpose of this study was to assess the efficacy of 150 mg of
      aspirin plus 100 mg of alteplase, administered as two intravenous bolus
      injections of 50 mg each given 30 min apart, and followed by intravenous heparin,
      on infarct-related coronary artery patency (Thrombolysis in Myocardial Infarction
      [TIMI] flow grade 3). BACKGROUND: Previous workers have shown in animals that
      reducing the duration of an infusion of recombinant tissue-type plasminogen
      activator increases the initial rate of thrombolysis, resulting in high early
      infarct-related coronary artery patency rates. The logical progression of this
      idea is bolus administration. METHODS: Consecutive patients presenting up to 6 h
      from the onset of symptoms were recruited for the study. Angiography was
      performed at 60 and 90 min after the first bolus and between 19 to 48 h after
      study entry. Patients were followed up for 1 month. RESULTS: At 60 min,
      angiography revealed infarct-related coronary artery patency of TIMI flow grade 3
      in 55 (86%) of 64 patients (95% confidence interval [CI] 75% to 93%) and TIMI
      flow grade 2 or 3 in 58 (91%) of 64 patients (95% CI 81% to 97%). At 90 min,
      infarct-related artery patency of TIMI flow grade 3 was achieved in 74 (88%) of
      84 patients (95% CI 79% to 94%) and TIMI flow grade 2 or 3 in 78 (93%) of 84
      patients (95% CI 85% to 97%). Two patients (2.4%) had early angiographic
      reocclusion whereas 10 (11.9%) had late reinfarction. Bleeding episodes were
      mostly minor, and there was no cerebrovascular bleeding. Five patients (6.0%)
      died within 1 month of the acute myocardial infarction. CONCLUSIONS: In 84
      patients with acute myocardial infarction, administration of 100 mg of double
      bolus (2 x 50 mg) alteplase, aspirin and heparin is associated with remarkably
      high early infarct-related coronary artery patency rates (TIMI flow grade 3) of
      86% and 88%, respectively, at 60 and 90 min.

PMID- 8277098
TI  - Variability of episodic ST segment depression in chronic stable angina:
      implications for individual and group trials of therapeutic efficacy.
AB  - OBJECTIVES: This study was conducted to quantify the variability of episodic ST
      segment depression in chronic stable angina and enable assessment of the impact
      of interventions in individual patients and clinical trials. BACKGROUND: Episodic
      myocardial ischemia can be detected by ST segment depression on ambulatory
      electrocardiographic (ECG) monitoring and may be important for the assessment of
      outcome. Variability of the number and duration of episodes has important
      implications for monitoring and therapeutic strategies. METHODS: We studied 36
      patients, aged 37 to 77 years (median 60), with stable angina and coronary artery
      disease by serial ambulatory ECG monitoring for a total of 415 days. A nested
      analysis of variance was carried out to assess the sources of spontaneous
      variation, and power function analyses were performed. RESULTS: During 415 days
      of monitoring, 1,882 episodes of ST segment depression were detected (mean
      frequency +/- SD, 4.5 +/- 4.1/day, duration 67 +/- 87 min/day, 25% in association
      with pain). Considerable variability was found within and between patients for
      both the number and the duration of ischemic episodes. For a patient monitored
      for 24 h before and after treatment, an 81% reduction in the number of episodes
      would be required to show a significant benefit; if monitoring were performed for
      4 days four times before and after therapy, a 46% decrease would be significant.
      In clinical trials, a true reduction of > or = 15% in ischemic episodes is
      required to have sufficient power to obtain statistical significance.
      CONCLUSIONS: The natural variability of transient myocardial ischemia in patients
      with chronic stable angina can be quantified and this information used to study
      the effectiveness of interventions in both individual patients and clinical
      trials.

PMID- 8277099
TI  - Characteristics and clinical significance of ambulatory myocardial ischemia in
      men and women in the general population presenting with angina pectoris.
AB  - OBJECTIVES: The aim of this study was to determine the frequency and prognostic
      importance of ambulatory myocardial ischemia and its association with
      cardiovascular risk factors in men and women in the general population presenting
      for the first time with typical angina pectoris. BACKGROUND: Previous studies in
      selected "low" and "high" risk patients with stable coronary heart disease report
      a wide range in the frequency of ischemia (24% to 82%) and there is no agreement
      about whether ambulatory ischemia is of prognostic importance for the generality
      of patients with stable angina. METHODS: Consecutive patients < or = 70 years of
      age from a randomly selected population with no previous coronary heart disease
      were assessed prospectively, and 96 patients with typical angina and 95 age-,
      gender- and practice-matched asymptomatic control subjects underwent 24-h
      ambulatory ST segment monitoring before antianginal therapy. All recordings were
      analyzed in blinded fashion. Follow-up evaluation of patients with angina to
      assess for revascularization, myocardial infarction and death was undertaken at a
      mean of 15.8 months (range 7 to 30) after the initial evaluation. RESULTS:
      Transient episodes of ischemic ST segment depression were detected in 50 patients
      (52%) with angina and 9 control subjects (9%). In patients with angina, 159
      episodes (71%) were silent, median duration of ischemia was 66 min (range 1 to
      782) and mean +/- SD ST depression was 2.4 +/- 1.1 mm. In logistic regression
      analysis, serum cholesterol (p < 0.05) and ischemia on exercise (p < 0.01) were
      independently associated with the presence of ambulatory ischemia in men with
      angina, but only the latter was significant in women; this may reflect a
      different pathophysiologic basis for ambulatory ischemia in women. During follow
      up, there were 29 events. Kaplan-Meier survival analysis revealed no significant
      difference in event-free survival between patients with angina who did and did
      not have ischemic episodes (66% vs. 72%, p = NS). CONCLUSIONS: This is the first
      study representative of new patients with angina pectoris in the general
      population and shows that ischemia during daily living activities is present in >
      50% of these patients but appears to be of no prognostic value.

PMID- 8277100
TI  - Systemic and cardiac neuroendocrine activation and severity of myocardial
      ischemia in humans.
AB  - OBJECTIVES: The purpose of this study was to assess the effect of different
      degrees of ischemia on circulating and cardiac neurohormones and vasotone.
      BACKGROUND: Neuroendocrine activation and subsequent systemic vasoconstriction
      may complicate ischemia. Whether this relates to severity of ischemia and
      subsequent cardiac dysfunction, and whether neurohormonal balance in the ischemic
      area changes, is unknown. METHODS: Fifty-six normotensive patients with coronary
      artery disease were evaluated during incremental atrial pacing. On the basis of
      ST segment changes, patients were classified in a nonischemic (n = 11) or
      ischemic group (n = 45), the latter patients were subsequently classified as
      lactate (n = 28) or nonlactate (n = 17) producing, to identify neurohormonal
      changes in the effluent of the ischemic myocardium. RESULTS: Angina occurred in
      55%, 82% and 82% of patients in the nonischemic, lactate- and nonlactate
      producing groups, respectively. Baseline hemodynamic variables and neurohormones
      were comparable in all groups, as were heart rate, rate-pressure product and
      coronary hemodynamic variables during pacing. In lactate producers, contractility
      did not improve, relaxation deteriorated, left ventricular filling pressure
      increased and cardiac output decreased during pacing, indicating more severe
      ischemia compared with that in nonlactate producers. Neurohormones did not change
      in the nonischemic group. In contrast, arterial and coronary venous
      catecholamines increased significantly more in lactate producers than in
      nonlactate producers (arterial norepinephrine by 68% vs. 36%, respectively).
      Moreover, arterial angiotensin II increased in lactate producers from a baseline
      mean +/- SEM of 6.8 +/- 0.9 to 9.7 +/- 1.6 pmol/liter (p < 0.05), accompanied by
      a sustained 23% increase in systemic resistance and arterial pressures. In
      lactate producers, baseline net cardiac norepinephrine release changed to net
      uptake during pacing (-0.05 +/- 0.02 vs. 0.06 +/- 0.05 nmol/min, p < 0.05).
      Epinephrine uptake increased in all patients with ischemia, albeit more in
      lactate producers. CONCLUSIONS: Circulating catecholamines and renin-angiotensin
      levels are activated, and systemic vasotone is increased in relation to the
      degree of ischemia. Cardiac epinephrine uptake increases, whereas net baseline
      norepinephrine release from the ischemic myocardium changes to net uptake.
      Modulation of this neurohormonal activation may provide an alternative mode to
      limit ischemia.

PMID- 8277101
TI  - Positron emission tomography detects evidence of viability in rest technetium-99m
      sestamibi defects.
AB  - OBJECTIVES: The purpose of this study was to determine the relative value of
      single-photon emission computed tomographic (SPECT) imaging at rest using
      technetium-99m methoxyisobutyl isonitrile (technetium-99m sestamibi) with
      positron emission tomography for detection of viable myocardium. BACKGROUND:
      Recent studies comparing positron emission tomography and thallium-201
      reinjection with rest technetium-99m sestamibi imaging have suggested that the
      latter technique underestimates myocardial viability. METHODS: Twenty patients
      with a previous myocardial infarction underwent rest technetium-99m sestamibi
      imaging and positron emission tomography using fluorine (F)-18 deoxyglucose and
      nitrogen (N)-13 ammonia. In each patient, circumferential profile analysis was
      used to determine technetium-99m sestamibi, F-18 deoxyglucose and N-13 ammonia
      activity (expressed as percent of peak activity) in nine cardiac segments and in
      the perfusion defect defined by the area having technetium-99m sestamibi activity
      < 60%. Technetium-99m sestamibi defects were graded as moderate (50% to 59% of
      peak activity) and severe (< 50% of peak activity). Estimates of perfusion defect
      size were compared between technetium-99m sestamibi and N-13 ammonia. RESULTS:
      Sixteen (53%) of 30 segments with moderate defects and 16 (47%) of 34 segments
      with severe defects had > or = 60% F-18 deoxyglucose activity considered
      indicative of viability. Fluorine-18 deoxyglucose evidence of viability was still
      present in 50% of segments with technetium-99m sestamibi activity < 40%. There
      was no significant difference in the mean (+/- SD) technetium-99m sestamibi
      activity in segments with viable (40 +/- 7%) and nonviable segments (49 +/- 7%, p
      = 0.84). Of the 18 patients who had adequate F-18 deoxyglucose studies, the area
      of the technetium-99m sestamibi defect was viable in 5 (28%). In 16 patients
      (80%), perfusion defect size determined by technetium-99m sestamibi exceeded that
      measured by N-13 ammonia. The difference in defect size between technetium-99m
      sestamibi and N-13 ammonia was significantly greater in patients with viable (21
      +/- 9%) versus nonviable segments (7 +/- 9%, p = 0.007). CONCLUSIONS: Moderate
      and severe rest technetium-99m sestamibi defects frequently have metabolic
      evidence of viability. Technetium-99m sestamibi SPECT yields larger perfusion
      defects than does N-13 ammonia positron emission tomography when the same
      threshold values are used.

PMID- 8277102
TI  - Use of the signal-averaged electrocardiogram for predicting inducible ventricular
      tachycardia in patients with unexplained syncope: relation to clinical variables
      in a multivariate analysis.
AB  - OBJECTIVES: The purpose of this study was to determine the predictors of
      electrically induced ventricular tachycardia in a large sample of patients with
      unexplained syncope and to examine the value of the signal-averaged
      electrocardiogram (ECG) in those patient subsets with varying pretest probability
      of ventricular tachycardia. BACKGROUND: In patients with unexplained syncope,
      electrophysiologic study can provide important diagnostic information, such as
      inducibility of ventricular tachycardia. The signal-averaged ECG can predict
      inducible ventricular tachycardia, but its utility has not been prospectively
      studied in a large group of patients with unexplained syncope. METHODS: At six
      hospitals, 189 consecutive patients with unexplained syncope underwent signal
      averaged ECG and electrophysiologic studies. RESULTS: Ventricular tachycardia was
      induced in 28 patients (15%). Univariate predictors of ventricular tachycardia
      included history of previous myocardial infarction, reduced left ventricular
      ejection fraction and abnormal signal-averaged ECG results. The signal-averaged
      ECG was the most sensitive test but had poor specificity. By multivariate
      analysis, the signal-averaged ECG and history of previous myocardial infarction
      were independently predictive. The risk of ventricular tachycardia increased 17
      fold in patients with a previous myocardial infarction who also had an abnormal
      signal-averaged ECG. In patients with no history of previous myocardial
      infarction, no additional testing was useful in identifying those at risk for
      inducible ventricular tachycardia. CONCLUSIONS: The signal-averaged ECG was the
      most sensitive noninvasive test available to predict sustained ventricular
      tachycardia at electrophysiologic study but was false positive in many patients.
      A history of previous myocardial infarction followed by the signal-averaged ECG
      was the most efficient screening process for predicting electrically induced
      ventricular tachycardia.

PMID- 8277103
TI  - Subjective memory complaints and personality traits in normal elderly subjects.
AB  - OBJECTIVE: To evaluate the relationship between objectively measured memory
      functions and subjective complaints of memory disturbance and whether subjective
      complaints are affected by some personality traits or affective states. DESIGN:
      Cross-sectional two-group comparison. SETTING: The city of Kuopio in Eastern
      Finland, considered representative of the urban elderly population of Finland.
      PARTICIPANTS: Originally 403 subjects aged 67-78 years from the random sample and
      then two matched study groups initially including eighteen subjects but only ten
      in the final analysis. MEASUREMENTS: Screening and follow-up examinations of
      subjects with and without subjective memory complaints: (1) Memory functions:
      Benton's visual retention test and the paired-associated learning subtest of
      Wechsler Memory Scale. (2) Memory complaints: Memory Complaint Questionnaire. (3)
      Personality traits and affective state: Two subscales from Minnesota Multiphasic
      Personality Inventory and Geriatric Depression Scale. RESULTS: Complaints of
      memory loss did not correlate with the actual memory performance in the tests.
      However, those subjects who most emphatically complained of memory disturbance
      had greater tendencies toward somatic complaining, higher feelings of anxiety
      about their physical health, and more negative feelings of their own competence
      and capabilities than those who did not complain of memory deterioration
      associated with aging. CONCLUSIONS: The study suggests that subjective feelings
      of memory impairment are more closely associated with personality traits than
      with actual memory performance in normal elderly people.

PMID- 8277104
TI  - Continence across the continents.

PMID- 8277106
TI  - Functional status care categories and national health policy.

PMID- 8277107
TI  - Lack of antibodies to HTLV-II in patients with dementia in Italy.

PMID- 8277105
TI  - Influence of diagnostic classification on outcomes and charges in geriatric
      assessment and rehabilitation.
AB  - OBJECTIVE: To determine if diagnostic classification is associated with different
      outcomes from treatment on a geriatric assessment unit (GAU) compared with usual
      care for elderly patients with acute illnesses. STUDY DESIGN: Reanalysis after
      post-hoc diagnostic classification of a randomized clinical trial with one year
      follow up. SETTING: Community hospital with rehabilitation facility. SUBJECTS: A
      total of 155 subjects, mean age 78 years and 78% female, of whom 58 subjects had
      a rehabilitation classification of their diagnoses and 97 had a medical or
      surgical classification. OUTCOME MEASURES: Mortality, nursing home use,
      activities of daily living, and charges for subsequent medical services. RESULTS:
      Mortality was decreased in persons with a rehabilitation classification who had
      received the GAU intervention. The GAU increased point-prevalence residence in
      the community for persons with a rehabilitation classification. For persons with
      a medical-surgical classification, the GAU intervention was associated with
      decreased cumulative use of nursing homes. However, GAU intervention was also
      associated with trends for increased charges in both diagnostic classification
      groups, even when adjusted for differential survival. CONCLUSION: Greater benefit
      from the GAU intervention on mortality and maintenance of residence in the
      community was observed in a group with a rehabilitation classification when
      compared with a group with a medical-surgical classification. These improved
      outcomes in the rehabilitation group were not accompanied by decreased charges
      for later medical services that could compensate for initial rehabilitation
      charges.

PMID- 8277108
TI  - Erythropoietin therapy for anemia in two nonagenarians.

PMID- 8277109
TI  - Differential diagnosis of dementia: a prospective evaluation of the DAT
      Inventory.
AB  - OBJECTIVE: To compare prospectively the concordance between the diagnosis of
      dementia based on clinical criteria and using the DAT Inventory. DESIGN, SETTING,
      AND PARTICIPANTS: A prospective study of 81 consecutive patients referred to a
      Memory Clinic. Only patients for whom a definitive diagnosis of dementia was
      established after 8 to 20 months follow-up were retained in the study (n = 76).
      MEASUREMENTS: The sensitivity, specificity, positive and negative predictive
      values, and overall diagnostic accuracy of the DAT Inventory were calculated.
      Kappa values were also computed. RESULTS: Based on all patients (n = 76),
      sensitivity and specificity were 71% and 95%, respectively, with 98% positive
      prediction, 56% negative prediction, 78% overall accuracy, and kappa of 0.54. Of
      21 cases not meeting NINCDS/ADRDA criteria for DAT, one patient with multi
      infarct dementia was misclassified as DAT on the DAT Inventory. Of 55 DAT cases
      (NINCDS/ADRDA criteria), 16 patients, predominantly very mild or mixed cases,
      were classified as non-DAT on the DAT Inventory. When mixed, very mild, and
      borderline cases were excluded (remaining n = 54), DAT Inventory sensitivity
      increased to 94%, and specificity remained unchanged at 95%, with 97% positive
      and 91% negative prediction, 94% overall accuracy, and kappa of 0.88.
      CONCLUSIONS: In general, scores above the designated cutoff point (> 14/20) on
      the DAT Inventory are consistent with a clinical diagnosis of DAT (NINCDS/ADRDA
      criteria). Concordance is best in cases of mild to moderate dementia (Clinical
      Dementia Rating 1-2). The Inventory is less discriminating as a differential
      diagnostic instrument in cases of very mild dementia, atypical presentations of
      DAT, or in cases of mixed pathology.

PMID- 8277110
TI  - The Timed Manual Performance test as a predictor of hospitalization and death in
      a community-based elderly population.
AB  - OBJECTIVE: To determine the usefulness of timed manual performance measurements
      (TMP) as predictors of health outcomes, hospitalization, and mortality in a
      large, heterogeneous sample of elderly people living in the community. DESIGN:
      Prospective cohort study. SETTING: Central North Carolina. PARTICIPANTS: 1,286
      community-dwelling older people. MEASUREMENTS: Demographic background, health
      problems, number of prescribed medications, perceived health, quality of life,
      and the TMP, a 27-item test that has been shown to predict functional dependency
      and need of health-care services in older people. RESULTS: During the 2-year
      follow-up period, 127 people died and 200 were hospitalized. Scores for those who
      were able to complete the original TMP, as well as scores for two shorter
      versions of the TMP, predicted mortality and, to a lesser extent, hospitalization
      within 2 years. For both original and shorter versions of the TMP, relative risk
      of death was approximately 2.5 times greater for those in the poorest performance
      quartile, as compared with the best performing quartile, when adjusted for age,
      gender, race, and number of prescribed medications. TMP tests and an index of
      IADL were independent predictors of death. CONCLUSIONS: TMP scores may be useful
      in the clinical setting as a vital sign of functioning, providing a means of
      targeting those individuals at increased risk of mortality.

PMID- 8277111
TI  - The appropriateness of oral fluoroquinolone-prescribing in the long-term care
      setting.
AB  - OBJECTIVE: To evaluate the appropriateness of ciprofloxacin-prescribing in the
      long-term care setting. DESIGN: Retrospective chart review. SETTING: A large
      academically oriented long-term care facility. PATIENTS: Institutionalized
      elderly patients with a mean age of 88 years. METHODS: One hundred orders were
      randomly selected for review from all ciprofloxacin orders initiated over a 3
      year period. Criteria for appropriateness of ciprofloxacin-prescribing were
      developed based on a comprehensive review of the medical literature. Evaluation
      of appropriateness of prescribing was based on the indication for therapy and the
      availability of more effective and/or less expensive alternative antibiotic
      regimens. Only information available to the physician at the time of the order
      was used to judge appropriateness. Abstracted medical records were evaluated
      independently by a geriatrician and an infectious diseases specialist. RESULTS:
      With respect to site of infection, the urinary tract accounted for 43% of all
      ciprofloxacin orders; the lower respiratory tract, 28%; and skin and soft-tissue
      infections, 17%. Only 25% of orders were judged appropriate. Twenty-three percent
      of orders were judged less than appropriate based on indication, and 49% due to
      the availability of a more effective and/or less expensive alternative antibiotic
      choice. There was insufficient information in the medical record to judge 3% of
      the orders. CONCLUSION: These results indicate less than optimal prescribing of
      oral fluoroquinolones in the long-term care setting, with potential consequences
      including the development of resistant bacterial strains and increased health
      care costs.

PMID- 8277112
TI  - The epidemiology of adverse and unexpected events in the long-term care setting.
AB  - OBJECTIVE: To describe the adverse and unexpected events reported by staff over a
      1-year period in a large, long-term care institution. DESIGN: A retrospective
      review of resident incident reports. SETTING: A 703-bed, academically oriented,
      long-term care facility. PATIENTS: Residents of the facility have a mean age of
      88.5 years, are 76% female, and have an average length of stay of 4.3 years.
      MEASUREMENTS AND MAIN RESULTS: Of the 3,390 adverse and unexpected events reports
      over the 1-year study period, falls (with and without associated injury) were the
      most frequently reported incidents, followed by non-fall-related injuries,
      medication-related events, and wandering episodes. While a large proportion of
      falls occurred in ambulating residents (47%), the majority occurred under
      different circumstances including falls from bed, wheelchair, and commode/toilet.
      Bruises and skin tears were the most frequently reported fall- and non-fall
      related injuries. The annual incidence rates for falls, fall-related injuries,
      and non-fall-related injuries varied according to resident care unit level, with
      semi-dependent residents experiencing the highest rates of falls and dependent
      residents experiencing the highest rates of non-fall-related injuries. Circadian
      patterns in the incidence of these events varied according to resident care
      level. CONCLUSIONS: Information regarding adverse and unexpected events in the
      long-term care setting can be organized into databases that allow analysis of
      patterns and trends. The results of these analyses may be helpful in targeting
      limited resources to areas of greatest need within an individual institution and
      for comparing quality of care across different long-term care facilities.

PMID- 8277113
TI  - Stroke inpatient rehabilitation: a comparison across age groups.
AB  - OBJECTIVE: To examine and compare the inpatient stroke rehabilitation experience
      of older adults (> or = 75 years) with that of young adults (< 65 years) and
      young-old adults (65-74 years). DESIGN: Cross-sectional descriptive study.
      SETTING: A large university-affiliated free-standing rehabilitation hospital.
      PARTICIPANTS: 260 adults who were admitted to inpatient stroke rehabilitation
      with a primary diagnosis of recent (< 120 days) stroke (ICD9 430-436). VARIABLES:
      Demographic data, diagnosis, time between stroke onset and rehabilitation
      admission, discharge disposition, and functional status on admission and
      discharge were obtained from the patient's medical record. Treatment intensity
      and type, length of stay, and primary payment source data were obtained from the
      patient's billing record. Three-month mortality data were available from the
      hospital's routine follow-up survey. MAIN RESULTS: Compared with the younger
      adults (< 65 yrs and 65-75 years), the older adults (> or = 75 years) were
      admitted to rehabilitation earlier and with comparable cognitive but poorer motor
      function. Rehabilitation treatment intensity (per day) and type were similar
      across age groups, but the older adults (> or = 75 years) had significantly
      shorter rehabilitation stays. Three-month survival was comparable across age
      groups, but the older adults (> or = 75 years) had poorer motor function at
      discharge and were more often discharged to a nursing home or required a paid
      caregiver. CONCLUSIONS: Age-associated factors may influence inpatient stroke
      rehabilitation referral, treatment, and outcome, particularly for patients over
      age 75. The cumulative effects of frailty and co-morbid disease upon stroke
      disability and treatment are possible explanations for the findings. The study
      provides evidence of a need for further investigation of stroke rehabilitation
      strategies for adults over 75 years old.

PMID- 8277114
TI  - A retrospective review of nosocomial infections in an acute rehabilitative and
      chronic population at a large skilled nursing facility.
AB  - OBJECTIVE: This study was undertaken to analyze infection rate, risk for
      acquisition of infection, and spectrum of infectious disease in two distinct sub
      populations within a large, metropolitan, long-term care skilled nursing facility
      (LTCSNF). DESIGN: A retrospective chart review over an 18-month period. SETTING:
      A large, metropolitan LTCSNF. PATIENTS: 786 acute rehabilitative patients and 554
      chronic patients. MEASUREMENTS: The study compared infection rate, risk for
      acquisition of infection, and the microbiology of the most common infections in
      the two sub-populations. Analyses comparing the infection rate in the
      rehabilitative population with the infection rate in the chronic population were
      performed by multiple regression. The dependent variable in these analyses was
      the number of infections. The length of time that the patient was at risk for
      infection was included as a covariate. MAIN RESULTS: Approximately 75% of
      patients in both groups were women. The median age was 80 years in the
      rehabilitative group, 85 years in the chronic group. Urinary tract infection,
      pneumonia, skin/soft tissue infection were the most common infections in both
      groups. Five hundred forty-seven patients in the rehabilitative group and 479
      patients in the chronic group had three or more underlying diseases.
      Enterobacteriaceae organisms were the most common isolates in urinary tract
      infectious episodes in both groups; mixed flora were the most common isolates for
      pneumonia and skin/soft tissue episodes in both groups. The calculated rate of
      infection for the rehabilitative and chronic groups was not significantly
      different (P = > 0.05). CONCLUSIONS: In concordance with other studies, urinary
      tract infection, respiratory infections, and skin and soft tissue infections were
      the most common in the long-term care facility. Analyses of two distinct
      populations within a single, large, teaching nursing facility revealed, however,
      that the rate of infection was not significantly different between the groups and
      that length of stay or presence of underlying disease was not predictive of
      infection.

PMID- 8277115
TI  - Case managers and physicians: communication and perceived problems.
AB  - OBJECTIVE: To describe case managers' perceptions of the physician-case manager
      relationship. DESIGN: A qualitative field study using in-depth open-ended
      interviews was used to elicit case managers' experiences and practices. A
      multidisciplinary team analyzed transcripts using an adaptation of the "grounded
      theory" approach of Glaser and Strauss. PARTICIPANTS/SETTING: Case managers were
      selected for interview using a maximum variation sampling strategy within an
      established state-wide case management agency. MAIN OUTCOME MEASURES: Transcript
      analysis allowed for the organization of observations into themes, which were
      merged across interviews to generate theses. RESULTS: Case managers report that:
      (1) The case manager role is poorly understood by physicians. (2) Physicians lack
      insight into the social and environmental aspects of home-bound elderly people.
      (3) Access to physician services is often difficult to obtain. (4) Power
      struggles occasionally surface in care planning. (5) Decisions by physicians and
      case managers regarding the care of frail elderly are often made from different
      agenda. CONCLUSIONS: From the perspective of case managers, gaps in
      interprofessional communication may hinder the optimal care of frail elderly
      individuals.

PMID- 8277116
TI  - Use of laxative medication in older persons and associations with low serum
      albumin.
AB  - OBJECTIVE: To study laxative use among older persons and the association of
      laxative intake with hypoalbuminemia. DESIGN: Cross-sectional study in a
      population-based cohort. SETTING: Community and institutions in the Iowa and
      Washington counties, Iowa site of the Established Populations for Epidemiologic
      Studies of the Elderly. PARTICIPANTS: Persons aged 71 years or older, who were
      interviewed at the 6th year of follow-up and for whom drug intake information was
      obtained (n = 2,529). MAIN OUTCOME MEASURES: Laxative medication use and
      prevalence of hypoalbuminemia. RESULTS: The prevalence rate of laxative use was
      8.8% in the community and 74.6% in nursing homes. Increasing age was
      independently associated with laxative use (odds ratio [OR] = 1.66, 95%
      confidence interval [CI] = 1.33 to 2.07 for a 10-year increase), after adjusting
      for gender, institutionalization, disability in activities of daily living, body
      mass index, and use of the following drugs: furosemide, benzodiazepines,
      antidepressants, codeine, and calcium antagonists. Laxative use was independently
      associated with hypoalbuminemia (OR = 3.17, 95% CI = 1.42 to 7.08) after
      adjusting for age, gender, anemia, number of comorbid conditions, disability in
      activities of daily living, body mass index, use of furosemide, and
      institutionalization status. Compared with those who never used laxatives, those
      who took laxatives only at the 6th year of follow-up were at increased risk of
      hypoalbuminemia (OR = 2.65, 95% CI = 1.04 to 6.77), and those who used laxatives
      at both the 3rd and 6th years of follow-up were at greatest risk (OR = 4.02, 95%
      CI = 1.53 to 10.06). CONCLUSION: Laxatives are used by large numbers of older
      persons, and the investigation on unknown adverse effects is important.
      Prospective studies are needed to confirm the association of laxative use with
      hypoalbuminemia found in this study and to assess the mechanisms of this
      association.

PMID- 8277117
TI  - Longitudinal study on oral health in subjects with Alzheimer's disease.
AB  - OBJECTIVE: To examine longitudinal oral health changes in unmedicated, generally
      healthy subjects with Alzheimer's disease (AD) and compare them to age- and
      gender-matched healthy, unmedicated control subjects. DESIGN: Oral health
      parameters were evaluated over 2 to 3 years and the results compared between
      subjects with AD and controls. SETTING: Clinical Center of the National
      Institutes of Health, Bethesda, Maryland. PARTICIPANTS: Twenty-one community
      dwelling subjects with a clinical diagnosis of AD and 21 age- and gender-matched
      control subjects. Neither population was being treated for any other systemic
      condition nor taking any prescription medications. MEASUREMENTS: Unstimulated and
      stimulated major salivary gland flow rates were measured, and gingival,
      periodontal, dental, and oral mucosal tissues assessed. MAIN RESULTS: In general,
      subjects with AD demonstrated decreased salivary flow rates and diminished oral
      health, but most longitudinal changes in oral health status were not
      significantly different than controls. CONCLUSIONS: Patients with AD are
      susceptible to a variety of oral health problems, and progression of AD can lead
      to a deterioration in oral health and function. These patients require aggressive
      preventive care to maintain function for as long as possible, which necessitates
      close cooperation among numerous health care professionals.

PMID- 8277118
TI  - Treatment of small cell lung cancer in the elderly.
AB  - OBJECTIVE: Since both the incidence of lung cancer and the proportion of the
      population over age 65 are increasing rapidly in North America, we undertook a
      retrospective review of elderly patients with small cell lung cancer (SCLC) in an
      attempt to assess the effect of age on treatment decisions, response, survival,
      and toxicity. DESIGN: Retrospective chart view. SETTING: Oncology Unit of a
      university-affiliated teaching hospital. PATIENTS: There were 123 patients age >
      70 years treated from 1976-88. Chemotherapy consisted of either cyclophosphamide,
      doxorubicin, and vincristine, or etoposide and cisplatin. RESULTS: There were 74
      patients aged 70-74, 35 aged 75-80, and 14 aged 80 years or older. No significant
      differences existed between the groups in sex, stage, performance status, or
      presence of co-morbid disease. Median survivals for patients with limited and
      extensive disease were 11.9 and 5.2 months, respectively (P = < 0.0001), with no
      significant difference for patients in any age group (P = 0.4). For both limited
      and extensive disease, survival correlated strongly with the treatment received.
      Twenty-five patients received no treatment (median survival 1.1 months), 20 had
      radiation only (median 7.8 months), and 27 patients had < 3 cycles of
      chemotherapy (median 3.9 months). Median survival for the 50 patients who had 4-6
      cycles was 10.7 months (limited disease 15.0 months, extensive disease 8.61
      months). In the Cox Model, survival correlated strongly with stage of disease and
      chemotherapy treatment (P < 0.0001), but only marginally with performance status
      (P < 0.077). Of the 77 patients who had chemotherapy, less than 50% in all age
      groups completed six cycles. Only two patients completed chemotherapy without a
      single dose reduction, and 76.7% required more than two reductions. CONCLUSIONS:
      Chemotherapy should not be withheld from elderly patients with SCLC on the basis
      of age. The survival of patients who receive chemotherapy is significantly longer
      than that of untreated patients even though frequent dose reductions for toxicity
      may be required. The survival benefit is due to treatment effect and is not due
      to a selection bias in the cohort of patients chosen for therapy.

PMID- 8277119
TI  - Serum insulin-like growth factor I in healthy older men in relation to physical
      activity.
AB  - OBJECTIVE: The serum level of insulin-like growth factor-I (IGF-I) is lower in
      old men than in young men. It has been theorized that this change may result in
      part from the lower level of physical activity in the elderly. The objective of
      the present study was to test this theory. DESIGN: Cross-sectional study.
      SETTING: Community-dwelling healthy men. PARTICIPANTS: Twenty-nine young men aged
      21-29 and 120 older men aged 58-98. A wide range of habitual physical activity
      was assured in the older men by recruiting them both in senior centers and in
      fitness centers. MEASUREMENTS: Serum IGF-I level was measured by
      radioimmunoassay. Physical activity was estimated as the sum of moderate, hard,
      and very hard activities in leisure and occupation during the previous week as
      determined by the interviewer-administered Seven Day Physical Activity Recall
      questionnaire. RESULTS: IGF-I was significantly higher (363.7 +/- 16 ng/mL, avg
      +/- SEM) in the young men than in the senior center older men (219.6 +/- 5 ng/mL)
      or in the fitness center older men (168.3 +/- 11 ng/mL) (P < 0.01). The level of
      IGF-I in the senior center older men was higher than that in the fitness center
      older men (P = 0.05). The physical activity of the fitness center older men
      (128.5 +/- 15 Kcal/kg/wk, avg +/- SE) was statistically similar to that of the
      young men (101.3 +/- 19 Kcal/kg/wk). The physical activity levels of both of
      these groups were significantly higher than that of the senior center older men
      (33.6 +/- 3 Kcal/kg/wk) (P < 0.010). Within none of the three groups was there a
      significant correlation between IGF-I and physical activity. When the two groups
      of older men were combined, there was, in fact, an inverse correlation of IGF-I
      and physical activity (P = 0.001). CONCLUSION: The data do not support the
      hypothesis that lack of physical activity is responsible for the decline in serum
      IGF-I with advancing age.

PMID- 8277120
TI  - Importance of assessment of metered-dose inhaler technique in the elderly.

PMID- 8277121
TI  - Secondary mania in late life.

PMID- 8277122
TI  - Fever of unknown origin in the elderly: lymphoma presenting as vertebral
      compression fractures.

PMID- 8277123
TI  - Postural control in older adults.

PMID- 8277124
TI  - The structure of health status among older adults: disease, disability,
      functional limitation, and perceived health.
AB  - This article builds on earlier conceptualizations of the structure of health
      status to propose a more complex, multiequation model that examines the
      interrelationships among its various dimensions. As such, the focus is not merely
      on the identification of the direct effects of a variety of factors on perceived
      health status, but on how the constructs of disease, functional limitation, and
      self-rated health interrelate. In so doing, we expose the inherent problems of
      several complex and contaminated items routinely included in applications of
      established functional health status measures. The source of these problems lies
      in the lack of specificity or conceptual clarity for the individual items in
      these established measures. Potential biases are discussed, and several methods
      and strategies for addressing these problems are explored. Alternative scales are
      constructed and their psychometric properties are presented. Researchers who rely
      on public use data bases containing these scales should be aware of the potential
      biases and either modify the scales or use other appropriate methodologies to
      control for the measurement contamination.

PMID- 8277125
TI  - Choosing optimal support groups: a review and reformulation.
AB  - There is considerable empirical research on the division of supportive and
      caregiving services among different network members. Yet the principles that
      govern the configuration of social support networks are still not well
      understood. Cantor's (1979) and Shanas' (1979) hierarchical-compensatory model
      and Litwak's (1985) task-specific model are among the more prominent formulations
      for explaining the choice of support groups. We propose that the former model is
      a special case of the latter one. The major conceptual features of both models
      are summarized here, followed by a qualitative review of 16 key empirical studies
      coupled with a meta-analysis to demonstrate the broader application of the task
      specific model.

PMID- 8277126
TI  - Kin and nursing home lengths of stay: a backward recurrence time approach.
AB  - There are numerous hypotheses about the role played by kin in decreasing the
      length of elderly persons' nursing home stays, yet few studies have explicitly
      examined the relationship between kin and episode length. Here we use backward
      recurrence time data from the Current Resident File of the 1985 National Nursing
      Home Survey to estimate models in which the hazard of leaving a nursing home
      depends upon covariates . Women admitted at age 65 or older stay, on average, 26
      months in an institution, while men have an average stay of 19 months.
      Controlling for demographic factors, insurance status, and various chronic and
      morbid conditions, we find that, on average, having a living spouse decreases the
      length of stay by four months for men and three months for women. Having a living
      child decreases the mean length of stay for women by three months, but has no
      effect on the mean length of stay for men. Findings underscore the importance of
      family members in shortening the lengths of time spent by older persons in
      nursing homes.

PMID- 8277127
TI  - The referral of minority adolescents to community mental health centers.
AB  - Few investigations have examined the referral of minority adolescents to
      community mental health clinics. This issue is especially critical in light of
      the increased attention given to mental health services for children and
      adolescents in recent years. The present study uses mental health clinic data
      from a large metropolitan area to explore whether African Americans and Mexican
      Americans entering mental health care do so through referrals that are more
      coercive than those made for Whites. The total sample consists of 2,460
      adolescents aged 13-17; the results indicate that African-American adolescents
      are more likely than Whites to be referred by an external agency. When types of
      external agencies are considered, African Americans enter community mental health
      care more often than Whites through referrals from social agencies; Mexican
      Americans enter more often than Whites through school referrals. This paper
      suggests that African-American adolescents' overrepresentation in community
      mental health clinics may in part be due to their disproportionate contact with
      social and legal agencies and the propensity of these agencies to rely more often
      on the mental health system than on families or schools. Among all variables
      considered in the analyses for this paper, poverty status demonstrated the most
      consistent and powerful association with coercive referrals.

PMID- 8277128
TI  - Re-thinking the analysis of intergenerational social mobility: a comment on John
      W. Fox's "Social class, mental illness, and social mobility".
AB  - The method of analyzing social mobility described by Fox (1990) is flawed in its
      adjustment for between-group differences in destination status when estimating
      the extent of the mentally ill's mobility as compared with the general
      population. Use of the recommended model with hypothetical data sets resulted in
      a significant finding when no overall upward or downward mobility occurred, and a
      non-significant result when the downward mobility of a psychotic group was
      contrived to be massive. An alternative model for the test of group differences
      in mobility is suggested within the framework of log-linear analysis commended by
      Fox (1990). This method indicated significantly more downward and less upward
      mobility in mentally ill groups when data from four studies were re-analyzed. We
      conclude that the weight of evidence from published studies supports the notion
      of social selection-drift, although this does not imply the inconsequence of
      social factors in the aetiology of schizophrenia (and other psychoses) or in its
      prognosis and occupational consequences.

PMID- 8277129
TI  - Higher rates of physical symptoms among homeless women do not appear to be due to
      reporting bias: a comment on Ritchey et al. (1991)

PMID- 8277130
TI  - Self-efficacy and health behavior among older adults.
AB  - Self-efficacy has a well-established, beneficial effect on health behavior and
      health status in young and middle-aged adults, but little is known about these
      relationships in older populations. We examined this issue as part of a
      randomized trial to determine the cost savings and changes in health-related
      quality of life associated with the provision and reimbursement of a preventive
      services package to 2,524 Medicare beneficiaries enrolled in Group Health
      Cooperative of Puget Sound. Baseline self-efficacy data were collected for all
      participants in five behavioral areas: exercise, dietary fat intake, weight
      control, alcohol intake, and smoking. Results reveal that efficacy and outcome
      expectations for these health behaviors are not independent. Correlational and
      factor analyses indicate two dimensions of efficacy expectations, one consisting
      of exercise, dietary fat, and weight control, and another consisting of smoking
      and alcohol consumption. Outcome expectations of the five behaviors form a single
      dimension. Older adults with high self-efficacy had lower health risk in all
      behaviors and better health. Regression analyses detected a positive association
      between socioeconomic status and health-related quality of life (p < .02), but
      the strength of the association declined (p < .11) after the self-efficacy
      measures entered the model, indicating that self-efficacy explains part of the
      association between socioeconomic status and health status. Interventions aimed
      at improving self-efficacy also may improve health status.

PMID- 8277131
TI  - Discussing sexual concerns with health care professionals: positive attitudes in
      healthy subjects.
AB  - Sexuality is an important part of human health and should be addressed in
      numerous aspects of nursing care. Many nurses have difficulty providing patients
      with care in the area of sexuality, however, and usually do not address sexual
      concerns unless the patient asks specific questions. This study explored the
      attitudes of healthy individuals toward physicians and nurses discussing sexual
      concerns with clients. Most subjects thought discussing sexual concerns with
      nurses was appropriate, and all subjects thought that physicians should discuss
      sexual concerns with clients. Regression analyses indicated that attitudes were
      not influenced by variables such as age, gender, or marital status. These
      findings suggest that nurses can feel comfortable addressing sexuality with many
      more of their clients and that when unsure about discussing sexuality with
      clients, nurses should refer clients to their physicians.

PMID- 8277132
TI  - The bath: a nursing ritual.
AB  - This article examines the bath as a nursing ritual, using examples from the
      literature from the 1880s to the present time. Selections from nursing
      periodicals and other literature are used to support the connections between past
      and present nursing practices in relation to bathing and hygienic care. The bath
      represents part of the essential character of nursing and is rooted in the
      beliefs, art, and science of the profession. It is a channel for many other
      nursing activities and responses, and as such, occupies a necessary part of
      nursing's repertoire and identity.

PMID- 8277133
TI  - Understanding autobiographical memories: a study of the reminiscences of elderly
      men.
AB  - This study examined the stability of autobiographical memory constructs and
      provided data about male styles of reminiscing that are useful for expanding the
      generalizability of the Autobiographical Memory Coding Tool. Six males ranging in
      age from 76 to 84 who lived in the community served as subjects. Subjects
      participated in two one-to-one reminiscence interviews that were conducted 8
      weeks apart. Interpretations formulated by this sample of elderly men were both
      validating and lamenting. Dominant themes in the transcripts were joys, social
      connections, difficulties, and choices. The frequency with which memories
      involving choice and lack of choice were verbalized suggest that control may be
      an important issue for this sample. The interpretations were quite stable with
      91% agreement between Time 1 and Time 2 transcripts.

PMID- 8277134
TI  - Caring: a vision of wholeness for nursing.
AB  - Caring as a new paradigm for nursing is rapidly gaining ascendance. As nurse
      scholars and practitioners recognize the power of caring, they are joining
      together in a "conspiracy" of caring. The purpose of this article is to set the
      stage for creative visioning that might generate new ways of thinking about
      caring, nursing practice, and research. A very brief review of caring scholarship
      in nursing over the last 15 years sets the context for the discussion of caring
      research and practice. It is suggested that when the phenomenon of interest is
      human caring, the perspective or vision of the scientist must necessarily change
      from a traditional, empirical view of what is real to a holistic vision of
      nursing as a human, caring science. The process for both personal and societal
      transformation is discussed.

PMID- 8277135
TI  - Amma therapy: a holistic approach to chronic fatigue syndrome.
AB  - A significant number of people suffering with chronic fatigue syndrome have
      become more and more discouraged by the traditional medical approach, which seems
      to lack the proper perspective on the disease. Unfortunately, very little
      published information is available about specific holistic health management
      practices used for these patients. It is the purpose of this article to examine a
      specific holistic practice, called Amma Therapy, as an alternative approach for
      the management of this syndrome.

PMID- 8277136
TI  - Meeting holistic health needs through a religious organization: the congregation.
AB  - Jesus's healing ministry is making a comeback in Christian congregations today.
      One method the church is using to facilitate this healing ministry is through the
      parish nurse ministry. The parish nurse model uses the holistic health concept
      that health is an interplay of body, mind, and spirit. The parish nurse ministry
      implements the gospel through health education, health counseling, patient
      advocacy, referrals, support groups, and the training of volunteers. The focus of
      this article is meeting the holistic health needs through a religious
      organization: the congregation. This article briefly reviews the concepts of
      holistic health and Christianity and healing, and it gives an example of
      implementing this concept in a congregation.

PMID- 8277137
TI  - Current concepts of the classification of affective disorders.
AB  - The introduction of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-III), which uses a descriptive approach to operational definitions of
      psychiatric diagnostic groups, is an important step forward. Still the present
      classification systems of DSM or the International Classification of Diseases
      (ICD) are preliminary. A systematic descriptive approach based on data collection
      as a foundation for diagnostic definitions is strongly recommended. Data-based
      definitions have a good change of surviving later changes of diagnostic fashion.
      Treatment studies will be more valuable when the course of a disorder is included
      in its definition. The diagnosis of depression has to include operationalized
      subthreshold syndromes, such as minor depression and recurrent brief depression.
      In the face of the elementary importance of the distinction between uni- and
      bipolar disorders, a development of the definition of hypomania is proposed.
      Based on this definition, bipolar disorders are more prevalent in the normal
      population than is commonly assumed. Most diagnostic subgroups of depression are
      artificial. They are not diagnostic entities, but subtypes of the same spectrum
      disorder. During his/her lifetime, a patient may therefore receive two or more
      diagnoses, but still suffer from a single disorder. Dual diagnoses, such as
      double depression and combined depression, define more severely affected patients
      with major depression, characterized by higher suicide attempt rates. Thus the
      differentiation of subgroups is more than an academic exercise but has a
      practical use.

PMID- 8277138
TI  - The morbidity and mortality of clinical depression.
AB  - Clinical depression is associated with social, occupational and physical
      impairment and mortality. Furthermore, data are reviewed which have related the
      severity of depressive symptoms, such as anhedonia, psychic anxiety, panic
      attacks, alcohol abuse, insomnia and diminished concentration in depressed
      patients, to suicide within 1 year. By contrast, hopelessness, suicidal ideation,
      and prior suicide attempts were related to suicide within 2-10 years after
      examination, but did not correlate with suicide within the first year of follow
      up. It is concluded that clinical depression continues to be associated with
      significant morbidity and mortality, despite progress which has been made in its
      treatment.

PMID- 8277139
TI  - A rational approach to the non-responding depressed patient.
AB  - At least 30% of patients with major depression fail to respond to conventional
      antidepressant medication, even when given adequate doses. Numerous factors have
      been implicated in treatment resistance including subclinical hypothyroidism,
      alcohol abuse, occult carcinoma, minor head injuries and the use of calcium
      channel blockers such as nifedipine. Lithium augmentation of traditional
      tricyclic antidepressants and selective serotonin re-uptake inhibitors such as
      fluoxetine are the most extensively investigated combinations used to treat non
      responsive depression. Other strategies are also briefly discussed.

PMID- 8277140
TI  - The rationale for long-term antidepressant therapy.
AB  - Most depressive disorders can be viewed as recurrent conditions that may reduce
      quality of life and productivity. Results of controlled clinical trials indicate
      that patients should receive 4-6 months of continuation therapy after remission
      of the acute phase of the illness. Patients at risk of recurrent episodes,
      however, should receive maintenance pharmacotherapy as depressive disorders
      appear to become more severe and potentially refractory with each new episode.
      This paper reviews a rationale and practical guidelines for long-term treatment
      of depressive disorders.

PMID- 8277141
TI  - How to improve the risk-benefit ratio of antidepressants.
AB  - To improve the risk associated with present antidepressant drugs, it is necessary
      to choose drugs that are selective and well tolerated in overdose, to look for
      contraindications, to adapt the dose progressively, to inform and supervise
      patients adequately, and to deal with risks due to the main pharmacological
      effects (anxiety, nervousness, sleep disturbances, suicide). With new drugs, risk
      improvement will probably be the result of greater selectivity. Improvements in
      efficacy could emerge during the development of new drugs, based on the
      monoaminergic and non-monoaminergic hypotheses. Much progress could be made,
      however, by questioning present practices. Optimizing dose, duration of
      treatment, co-medication, strategies for non-responders, and compliance,
      decreasing onset of action and targeting patients may help improve the efficacy
      of present antidepressant drugs.

PMID- 8277142
TI  - Severity of depression and response to fluoxetine.
AB  - Pooled data from multiple, double-blind clinical trials comparing fluoxetine with
      either placebo, a tricyclic antidepressant (TCA) or both in patients with major
      depression were analyzed to assess the efficacy of these treatments in mild,
      moderate and severe depression. Fluoxetine-treated patients showed statistically
      significantly higher rates of response and remission than placebo-treated
      patients within all three severity subgroups. There were no differences in
      response or remission rates between fluoxetine and TCAs, regardless of symptom
      severity. Thus, the efficacy of fluoxetine was superior to placebo and similar to
      TCAs in mild, moderate and severe major depression.

PMID- 8277143
TI  - A double-blind trial of fluoxetine, 20 mg, and placebo in out-patients with DSM
      III-R major depression and melancholia.
AB  - As part of a study in which reduced rapid eye movement latency was used to
      predict treatment response, fluoxetine and placebo were compared in 89
      outpatients with major depression with (n = 52) and without (n = 37) DSM-III-R
      melancholia, to determine whether the presence or absence of melancholia
      predicted antidepressant and/or placebo response. Following a 2-week, single
      blind placebo lead-in, men and women were assigned by random allocation to double
      blind fluoxetine, 20 mg/day, or placebo for 8 weeks. Fluoxetine was statistically
      significantly superior to placebo in patients with melancholia (endpoint change
      in the Montgomery-Asberg Depression Rating Scale [MADRS] score, response rates
      and remission rates). A weekly analysis demonstrated statistical superiority of
      fluoxetine compared with placebo at week 3 and continuing for the remainder of
      the study. Fluoxetine was statistically significantly more likely to reduce
      suicidal ideation compared with placebo, using the MADRS item 10 (suicidal
      ideation question).

PMID- 8277144
TI  - Analysis of the Hamilton Depression Rating Scale factors from a double-blind,
      placebo-controlled trial of fluoxetine in geriatric major depression.
AB  - Major depression during later life represents a clinical challenge. Conventional
      antidepressant pharmacotherapy is relatively less well tolerated in geriatric
      patients compared with younger patients. Despite the striking impairments
      associated with this disorder, clinical investigations into the relative risk
      benefit ratio of various depression treatment strategies have been limited. In
      this multicentre, placebo-controlled, double-blind trial with fluoxetine, 671
      major depressed (DSM-III-R-compatible) outpatients aged 60 years or older were
      evaluated. The 21-item Hamilton Depression Rating Scale (HAMD21) response (p =
      0.014) and remission (p = 0.008) criteria favoured fluoxetine over placebo.
      Analysis of the treatment effect on change in the HAMD21 factors
      (anxiety/somatization, cognitive disturbance, psychomotor retardation, and sleep
      disturbance) revealed advantages for fluoxetine within the cognitive disturbance
      and psychomotor retardation factors. Overall, the rate of discontinuation for an
      adverse event between fluoxetine (11.6%) and placebo (8.6%) was not statistically
      significant. Baseline HAMD21 factor scores were not predictive of adverse events
      leading to premature treatment discontinuation. Fluoxetine, 20 mg/day, is a well
      tolerated and effective treatment option in the management of geriatric major
      depression.

PMID- 8277145
TI  - The effects of renal and hepatic disease on the pharmacokinetics, renal
      tolerance, and risk-benefit profile of fluoxetine.
AB  - Renal and hepatic diseases have a significant impact on the plasma concentration
      profiles and the dose requirements for almost all drugs. This paper reviews the
      effect of these diseases and their associated physiological derangements on the
      pharmacokinetics of fluoxetine and norfluoxetine. Metabolic studies of fluoxetine
      in man show that more than 70% of the radiolabelled compound is excreted in the
      urine. Most of the urinary radiolabelled products are metabolites and not the
      parent compound nor its active metabolite, norfluoxetine. Cirrhosis of the liver
      significantly reduces the clearance of fluoxetine and norfluoxetine, but mild,
      moderate, or severe renal dysfunction does not affect fluoxetine or norfluoxetine
      pharmacokinetics. Daily administration of fluoxetine, 20 mg, for more than 2
      months to renally impaired, depressed patients (who require haemodialysis)
      produces steady-state fluoxetine and norfluoxetine plasma concentrations that are
      comparable to the concentrations in depressed patients with normal renal
      function. Renal function is not an important determinant of the steady-state
      concentrations of fluoxetine or norfluoxetine, though the concentrations may be
      higher in patients with significantly impaired liver function.

PMID- 8277146
TI  - Adverse events and treatment discontinuations in fluoxetine clinical trials.
AB  - A re-analysis of the profile of adverse events observed in controlled clinical
      trials in summarized. The data confirm that the side-effects of fluoxetine
      therapy are different from those of the tricyclic antidepressants (TCAs), both in
      type and frequency. Moreover, the superior tolerability of fluoxetine compared
      with the TCAs is confirmed by the significantly lower rate of premature
      discontinuation in the fluoxetine-treated patients than in the TCA-treated
      patients.

PMID- 8277147
TI  - Fluoxetine: activating and sedating effects.
AB  - Serotonin uptake inhibitors are generally considered activating antidepressants.
      To assess the rates and temporal patterns of activation and sedation as well as
      dose-effect relationships, adverse event data were evaluated from a fixed-dose
      study comparing placebo and fluoxetine, 5, 20 and 40 mg/day, in the treatment of
      major depressive disorder (n = 363) and the pooled data from two fixed-dose
      studies comparing placebo and fluoxetine, 20, 40 and 60 mg/day, in the treatment
      of major depressive disorder (n = 746). The adverse events 'nervousness',
      'anxiety', 'agitation' and 'insomnia' were considered indicative of activation;
      'somnolence' and 'asthenia' were considered indicative of sedation. Activation
      and sedation were both statistically significant treatment-emergent phenomena (p
      < or = 0.05), but dose-effect relationships differed. Activation rates were
      relatively stable between 5 mg/day and 40 mg/day, but they increased at 60
      mg/day. Sedation rates increased linearly up to 40 mg/day, and then were
      comparable at 40 mg/day and 60 mg/day. Discontinuations due to either phenomenon
      were uncommon. The temporal patterns of first occurrences and persistence of
      activation and sedation differed. First occurrences of activation peaked early
      and declined over time at all doses. First occurrences of sedation also peaked
      early at all doses, but there may have been greater variability in first
      occurrences of sedation over time in patients receiving lower doses. The
      persistent occurrences of sedation may decline less over time than the persistent
      occurrences of activation.

PMID- 8277148
TI  - Fluoxetine not associated with increased aggression in controlled clinical
      trials.
AB  - A comprehensive meta-analysis was performed to address the possible association
      of fluoxetine with violence or aggression. Data from the United States
      Investigational New Drug Clinical Trial Databases for approved and potential
      indications (depression, obesity, bulimia nervosa, obsessive-compulsive disorder,
      smoking cessation, alcoholism; n = 3992) were evaluated. Statistically
      significantly fewer fluoxetine-treated patients (0.15%) than placebo-treated
      patients (0.65%) experienced events suggestive of aggression (hostility,
      personality disorder, antisocial reaction). A relative risk analysis indicated
      that aggression events were four times more likely to occur in placebo-treated
      patients than in fluoxetine-treated patients. Although the possibility that some
      rare phenomenon was not detected cannot be excluded, this meta-analysis did not
      show fluoxetine to be associated with an increased risk of emergence of violent
      or aggressive behaviour.

PMID- 8277150
TI  - Pharmacotherapy of bulimia nervosa--experience with fluoxetine.
AB  - A number of compounds having an effect on serotonergic transmission have been
      shown to have a beneficial therapeutic action in patients with bulimia nervosa.
      Many previous studies, however, have suffered from methodological shortcomings,
      in particular small population sizes. This article reviews present data which
      suggest that fluoxetine is effective in the treatment of bulimia nervosa. Two
      trials of unprecedented size (n = 387 and 398, respectively) have recently been
      reported. These two studies show that fluoxetine, 60 mg daily, has a clear
      beneficial effect on behavioural and other (attitudinal) measures of bulimic
      symptomatology, and that this dose of fluoxetine is well tolerated in patients
      with bulimia nervosa. The role of pharmacotherapy in the long-term treatment of
      this disorder and the relative roles of pharmacotherapy and psychotherapy in
      treating bulimia nervosa are also discussed.

PMID- 8277149
TI  - Comorbid anxious signs and symptoms in major depression: impact on functional
      work capacity and comparative treatment outcomes.
AB  - Psychological distress is a driver both of direct and indirect health care costs.
      Depression compromises functional well-being, such as work productivity. Comorbid
      anxious features often complicate the recognition of depression and may herald a
      poor prognosis. We report the results of a cross-sectional naturalistic study to
      determine the impact of three interventions (no antidepressant, fluoxetine, or
      tricyclic antidepressant therapy) on relative risk of work days lost in 454
      French outpatients with either major or minor depression. Most depressed patients
      also manifested anxious features (76% with a Hamilton Rating Scale for Anxiety
      score > or = 12). The presence of anxiety was related to the severity of
      depression, work absenteeism, and current social instability. Depression severity
      (Hamilton Rating Scale for Depression score > or = 26, including the
      contributions of anxious symptoms), psychiatric comorbidity, and psychomotor
      retardation best predicted continued work absenteeism. Patients with major
      depression were more likely to receive an antidepressant if they had a past
      history of depressive episodes and/or previous work disability. Patients with
      minor depression were less likely to receive drug therapy than patients with
      major depression, despite their current work disability. Among patients who
      received fluoxetine or a tricyclic antidepressant for at least 8 weeks,
      fluoxetine was associated with statistically significantly lower mean anxiety and
      depression scores and fewer work days missed.

PMID- 8277151
TI  - Pharmacotherapy of obsessive compulsive disorder--experience with fluoxetine.
AB  - Recent epidemiological data have shown that obsessive compulsive disorder (OCD)
      has a lifetime prevalence of 2.5-3.0%. Compounds having an effect on serotonergic
      neurotransmission have demonstrated a reproducible therapeutic effect in OCD.
      Most recent attention has been focused on the specific serotonin re-uptake
      inhibitor (SSRI) class of compounds. The pooled data from two recently completed
      placebo-controlled studies of the SSRI, fluoxetine, have demonstrated clear
      evidence of a clinically valuable therapeutic effect in patients with OCD.
      Combined efficacy and safety data suggest that fluoxetine, 20 mg/day, will be
      effective in many patients. The therapeutic response emerges slowly and increases
      gradually. Data from extension studies suggest that, in some patients, an optimal
      response may only be achieved with higher daily doses of fluoxetine. Clinical
      response has been shown to be sustained over periods of 9 months of treatment and
      following withdrawal in an open-label trial. Fluoxetine is safe and well
      tolerated in this group of patients.

PMID- 8277152
TI  - Fluoxetine in obsessive compulsive disorder in adolescents.

PMID- 8277153
TI  - Fluoxetine: the relationship between response, adverse events, and plasma
      concentrations in the treatment of bulimia nervosa.

PMID- 8277154
TI  - Treatment of premenstrual syndrome with fluoxetine: an open study.

PMID- 8277155
TI  - Impact of fluoxetine on work loss in depression.

PMID- 8277156
TI  - Placebo-controlled trial of lithium augmentation of fluoxetine and lofepramine.

PMID- 8277157
TI  - The combination of fluoxetine and lithium in clinical practice.

PMID- 8277158
TI  - Development and validation of a brief screening scale for depression in the
      elderly physically ill.

PMID- 8277159
TI  - Depression in elderly physically ill in-patients: a 12-month prospective study.

PMID- 8277160
TI  - Assessment of quality of life in the treatment of major depressive disorder with
      fluoxetine, 20 mg, in ambulatory patients aged over 60 years.

PMID- 8277161
TI  - Effects of fluoxetine on psychomotor performance, cognitive function and sleep in
      depressed patients.

PMID- 8277162
TI  - Three types of early termination of antidepressant drug treatment.

PMID- 8277163
TI  - [Bologna operation].
AB  - Thirty cases of urinary incontinence and genital prolapse have been treated using
      Bologna's method. The authors describe this operation. The post-operative
      controls were based on the clinical state of the patient and in ten cases on the
      urodynamic tests. Anatomical result was very satisfactory. In all but one case
      the abdominal pressure transmission defect to the upper urethral was corrected
      without deterioration of maximal urethral pressure.

PMID- 8277164
TI  - [Internal drainage of urine in cases of complicated urinary stasis caused by
      pregnancy].
AB  - In 14 women with sympthomatic hydronephrosis due to pregnancy (calyx diameter 1
      2,6 cm) an internal urinary drainage was carried out during the second half of
      pregnancy. Retrograde stenting was placed per cystoscopy in all cases. Follow-up
      examinations were taken weekly for the first two weeks and further on biweekly.
      Primary stenting was possible in 12 out of 14 cases, and in two patients
      dilatation of the ureteral orifice was necessary. 11 out of 14 patients suffered
      from complications such as severe dysuria (9), urinary tract infection (7),
      persisting lumbar pain plus catheter lumen obstruction (6 each) as well as
      catheter migration (3). Long-term follow-up showed that urinary tract obstruction
      was relieved by stenting in only 6 out of 14 patients. Sufficient urinary
      drainage by so called double-J ureteral stents was achieved in less than half of
      the cases. Moreover, there was a complication rate of more than 75%. Taking these
      results into consideration, internal drainage of complicated pregnancy
      hydronephrosis needs careful evaluation.

PMID- 8277165
TI  - [Retrocaval ureter. Apropos of 6 cases].
AB  - The authors report six cases of retrocaval ureter discovered in quite various
      circumstances. A genital malformation associated to the retrocaval ureter was
      found in only one case. Five of our six patients were operated. Four of them
      underwent uncrossing of the ureter relative to the vena cava, and a patient
      underwent nephrectomy because her kidney was destroyed. The sixth patient was not
      operated because there was no impact on the excretory cavities of the kidney.
      This series and the review of the literature allow specifying the course of
      action for this pathology.

PMID- 8277166
TI  - [Treatment of iatrogenic obstructions of the ureter following hysterectomy].
AB  - Ureteral injury after abdominal hysterectomy has been observed in 14 patients
      between 1988 and 1992. Open surgery, percutaneous nephrostomy, double pigtail
      stent insertion using antegrade and retrograde route, and balloon dilatation were
      used for treatment. The experience of the authors is reviewed.

PMID- 8277167
TI  - Sertoli cell tumor in an HIV+ man.
AB  - A 31 year old human immunodeficiency virus positive (HIV+) patient presented with
      an asymptomatic left testicular mass. Radical orchiectomy was performed, and
      pathology revealed a Sertoli cell tumor. This unique case prompted a review of
      the literature on testicular tumors in HIV patients, with special emphasis on
      incidence, tumor type and therapeutic alternatives.

PMID- 8277168
TI  - [Cystic lymphangioma of the scrotum. Apropos of a case].
AB  - The authors present the case of a cystic lymphangioma in the scrotum, a tumor
      which usually occurs in the neck, but is rarely observed in this region. Patient
      was a 22 year-old man, admitted for fever and a mass within the scrotum. The
      tumor was completely resected and no recurrence has been observed after a 6 month
      follow-up.

PMID- 8277169
TI  - [Retroperitoneal benign schwannoma].
AB  - The authors report about one case of retroperitoneal benign schwannoma located
      near the right kidney and causing renovascular arterial hypertension. The
      diagnosis of benign schwannoma, which is unfrequent in the absence of
      Recklinghausen's disease, was established after the pathological study of the
      complete specimen including the right kidney.

PMID- 8277170
TI  - [Radiological exploration of hematuria].
AB  - Hematuria is defined as the presence of blood in urine. Its site of origin can be
      in any point of the urinary tract. Its discovery leads to clinical, biological
      and radiological investigations. The causes of hematuria are dominated, in terms
      of frequency, by urinary infection and lithiasis. The risk of associated lesions,
      especially of a tumor, must lead to regarding them as excluding diagnoses.
      Besides the so-called "medical" hematurias of glomerular origin (hematuria with
      proteinuria and cylinder casts) and hematurias occurring during a first episode
      of cystitis in women, the radiological exploration of "surgical" hematuria is
      systematic and always begins with an IVP. When the IVP is normal, a cystoscopy is
      most often made. The other radiological examinations (CT, Doppler ultrasound) are
      performed only according to the findings of IVP and cystoscopy. Arteriography
      combined with renal phlebography is indicated if the assessment is negative in
      case of recurrent hematuria or of massive hematuria. It is mainly aimed at
      detecting a vascular malformation. When this exploration is completed, an
      etiology is found is about 90% of all cases.

PMID- 8277171
TI  - Look-back investigation after human immunodeficiency virus seroconversion in a
      pediatric dentist.
AB  - Routine military screening identified human immunodeficiency virus (HIV)
      infection in an asymptomatic dentist who had three prior negative antibody tests.
      A look-back investigation evaluated the provider and the practice and provided
      notification, counseling, and HIV testing for patients. Test results were linked
      to dental procedures categorized by levels of invasiveness. Of 1631 patients
      tested, all were negative for antibody to HIV. Analysis of 12,164 procedures on
      876 patients determined 20.5% of patients had procedures from the highest stratum
      of invasiveness; 42% had only low-risk exposure. Stratification of the degree of
      invasive exposure and clinical evaluation of disease stage in the infected health
      care worker are important in look-back investigations. The early stage of disease
      in the provider, the adherence to infection control precautions, and the low
      percentage of invasive procedures may have contributed to the lack of
      transmission. These results are consistent with current assessment that risk of
      transmission of HIV during invasive medical procedures is low.

PMID- 8277172
TI  - Bactericidal/permeability-increasing protein inhibits induction of macrophage
      nitric oxide production by lipopolysaccharide.
AB  - A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing
      protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO)
      production elicited by lipopolysaccharide (LPS) plus interferon-gamma (IFN
      gamma). Normal mouse plasma amplified NO synthesis (measured as NO2- release) at
      LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein
      (LBP) partially inhibited NO2- release in the presence of normal mouse plasma.
      rBPI23 (1 microgram/mL) effectively inhibited LPS-dependent NO2- release in the
      presence or absence of normal mouse plasma. Fifty percent inhibition of IFN
      gamma/LPS-elicited NO2- production or of binding of fluoresceinated LPS was
      obtained with approximately 0.2 microgram/mL rBPI23. These results provide a
      basis for studies of rBPI23 effects on NO synthase activity in murine models of
      gram-negative sepsis.

PMID- 8277173
TI  - The presence of K54 capsular polysaccharide increases the pathogenicity of
      Escherichia coli in vivo.
AB  - Proven isogenic capsule-negative derivatives (CP9.29, CP9.108, CP9.137, CP9.171,
      CP9.443, and CP9.C56), generated from an O4/K54/H5 blood isolate (CP9) of
      Escherichia coli by IS50L::phoA (TnphoA)-mediated transposon mutagenesis, were
      used to assess the function of a non-K1 capsule in three animal models.
      Intraperitoneal injection of CP9 (K54+) into mice resulted in an LD50 at 24 h of
      5.5 x 10(6) cfu compared with LD50s of 2.6 x 10(7) cfu and 3.8 x 10(7) cfu for
      CP9.108 (K54-) and CP9.C56 (K54-) (P < .001). CP9 was cleared less rapidly from
      the bloodstream, after intravascular injection, than was CP9.108 (P < .01). In
      the rat granuloma pouch model, CP9 could proliferate from starting inocula as low
      as 1.0 x 10(3) cfu/mL. In contrast, capsule-deficient derivatives underwent
      transient log kills with starting inocula as high as 1.0 x 10(6) cfu/mL. Because
      proven isogenic strains were evaluated, a clear contribution of the K54 capsular
      polysaccharide to virulence in vivo is demonstrated.

PMID- 8277174
TI  - Epidemiology of community-acquired Clostridium difficile-associated diarrhea.
AB  - The epidemiology of clinically recognized community-acquired Clostridium
      difficile-associated diarrhea was assessed in a retrospective cohort study of
      members of a health maintenance organization (HMO). Potential cases were
      identified through positive toxin assay results and confirmed by review of
      automated full-text medical records. Of 51 cases identified (7.7 per 100,000
      person-years), 42 (82%) were diagnosed and treated exclusively in the ambulatory
      care setting; 33 cases occurred within 42 days after 494,491 exposures to
      antibiotics dispensed by an HMO pharmacy. Antibiotic-specific attack rates varied
      from 0 to 2040 cases per 100,000 exposures. Increased age was associated with C.
      difficile-associated diarrhea (P < .001). Age-adjusted antibiotic-specific attack
      rates were at least 10-fold higher (P < .05) for nitrofurantoin, cefuroxime,
      cephalexin plus dicloxacillin, ampicillin/clavulanate plus cefaclor, and
      ampicillin/clavulanate plus cefuroxime than for ampicillin or amoxicillin;
      several other antibiotics were associated with similar but not significantly
      increased risks.

PMID- 8277175
TI  - Analysis of plasmin(ogen) acquisition by clinical isolates of group A
      streptococci incubated in human plasma.
AB  - Group A streptococci isolated from throat swabs or blood cultures were compared
      for the expression of plasmin(ogen) receptors. The majority of isolates bound
      125I-labeled Lys-plasmin and 125I-labeled Lys-plasminogen while displaying
      minimal reactivity with 125I-labeled Glu-plasminogen. All streptococcal isolates
      could acquire surface enzymatic activity when incubated in human plasma but not
      if the plasma had been depleted of plasminogen. The ability to acquire surface
      enzymatic activity was limited by the quantity of streptokinase in the reaction
      mixture. There was no statistically significant difference between group A
      streptococci isolated from throat swabs and those from blood cultures with
      respect to their interaction with components of the fibrinolytic system in human
      plasma. However, these isolates could be divided into two groups based on their
      ability to acquire surface enzymatic activity when incubated in plasma with
      exogenous streptokinase. Surprisingly, the acquisition of surface enzymatic
      activity when incubated in plasma containing streptokinase was not always
      correlated with the plasmin(ogen) binding capacity determined by direct binding
      of radiolabeled ligands. Analysis of this phenomenon suggests that group A
      streptococci can use diverse mechanisms to acquire plasmin(ogen)-dependent
      enzymatic activity.

PMID- 8277176
TI  - Effect of CL 184,005, a platelet-activating factor antagonist in a murine model
      of Staphylococcus aureus-induced gram-positive sepsis.
AB  - Experiments using a murine model of heat-killed Staphylococcus aureus-induced
      gram-positive bacterial sepsis indicate that the lethal bacterial effects can be
      prevented if mice are pretreated with CL 184,005, a platelet-activating factor
      (PAF) antagonist. CL 184,005 was ineffective when administered after bacterial
      challenge. Plasma of mice pretreated with CL 184,005 contained significantly less
      tumor necrosis factor (TNF), suggesting that CL 184,005 interferes with TNF
      synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased
      by pretreatment with CL 184,005. Although TNF levels were significantly decreased
      in mice treated with CL 184,005, interleukin-6 levels in serum were significantly
      increased. Athymic mice were also susceptible to the lethal effects of S. aureus,
      suggesting that T cells were not involved. When rats rendered hypotensive with S.
      aureus were treated with CL 184,005, their blood pressure was normalized. Mice
      treated with enterotoxin B were not protected if they were pretreated with CL
      184,005; however, TNF levels in these mice were significantly lower, suggesting
      that mediators other than PAF and TNF may contribute to the lethal effects of
      enterotoxin.

PMID- 8277177
TI  - Differential expression of proinflammatory cytokines and their inhibitors during
      the course of meningococcal infections.
AB  - Circulating concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)
      1 beta, IL-6, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptors p55
      (sTNFr-55) and p75 (sTNFr-75) and ex vivo production of TNF, IL-1, IL-6, and IL
      1ra using a whole blood culture system were measured during the acute and
      convalescent stages of meningococcal infection. Circulating TNF and IL-1 were
      below detection level, whereas IL-6 and IL-1ra, sTNFr-55, and sTNFr-75 were
      increased at admission. The ex vivo production of proinflammatory cytokines TNF,
      IL-1, and IL-6 was suppressed at admission and restored gradually during
      recovery. On the contrary, the production of the antiinflammatory IL-1ra was
      increased at admission. The elevated concentrations of both IL-1ra and sTNFr
      early in the course of infection suggest a regulatory role for these
      antiinflammatory compounds. The observed down-regulation of the ex vivo
      production of TNF, IL-1, and IL-6 and up-regulation of the production of IL-1ra
      in the acute stage may indicate a protective regulation mechanism.

PMID- 8277178
TI  - Cryptosporidium parvum infection of intestinal epithelium: morphologic and
      functional studies in an in vitro model.
AB  - A monolayer of mature polarized colonic epithelial cells (T84) able to generate
      and maintain a barrier to macromolecular flow was used to study pathophysiologic
      events that occur on microvillus cell exposure to Cryptosporidium parvum. By 24
      48 h, several life cycle forms were seen in parasitophorous vacuoles near the
      apical cell surface, along with a time- and oocyst dose-dependent reduction in
      epithelial barrier function. As few as 10(5) organisms constituted a successful
      infecting dose, and heat inactivation of organisms markedly reduced the monolayer
      barrier alteration. Horseradish peroxidase flux studies demonstrated a
      substantial increase in macromolecular permeability of the monolayer, and lactate
      dehydrogenase determinations indicated modest injury of the T84 epithelial cells
      on exposure to oocysts. Thus, disruption of the epithelial cell barrier, not just
      opening of transcellular channels for ion flow as reported previously, is
      responsible for the effects of C. parvum oocysts on intestinal epithelium.

PMID- 8277179
TI  - Treatment with albendazole for intestinal disease due to Enterocytozoon bieneusi
      in patients with AIDS.
AB  - To determine the efficacy and safety of albendazole for treatment of intestinal
      microsporidosis due to Enterocytozoon bieneusi, 29 patients with AIDS were
      studied. All had chronic diarrhea, weight loss, and evidence of malabsorption.
      After 1 month of treatment with albendazole (400 mg orally twice a day), the mean
      number of bowel movements decreased from 7.0 to 3.8 stools/day (P < .0001) and
      the mean weight gain was 0.56 kg (P = .259). Albendazole at this dose did not
      clear E. bieneusi on follow-up small-bowel biopsies, but ultrastructural studies
      revealed an apparent decrease in parasite burden in 2 patients and an increased
      proportion of dividing plasmodia in 5 patients. There were no significant adverse
      events associated with this dose of albendazole. A formal double-blind placebo
      controlled study using higher doses has recently been approved and will soon be
      underway (AIDS Clinical Trial Group protocol 207).

PMID- 8277180
TI  - Relationship between load of virus in alveolar macrophages from human
      immunodeficiency virus type 1-infected persons, production of cytokines, and
      clinical status.
AB  - The level of human immunodeficiency virus type 1 (HIV-1) in lymphocytes and
      mononuclear phagocytes (MP) from the blood and pulmonary alveoli from 14 HIV-1
      infected subjects during early (asymptomatic) and late (AIDS) stages of disease
      and the relationship between virus burden in MP and cytokine expression were
      assessed. Among asymptomatic subjects, HIV-1 was undetectable or low in both
      blood monocytes and alveolar macrophages (AM). Among subjects with AIDS, there
      was a significant increase of HIV-1 in AM but not monocytes. The level of HIV-1
      in blood lymphocytes was higher than in either monocytes or AM. AM (but not
      monocytes) expressed increased levels of lipopolysaccharide-stimulated cytokine
      mRNA (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) during both
      early and late stages of HIV-1 infection regardless of virus load. AM thus may
      serve as a reservoir for virus in late stages of disease yet contribute to the
      immunopathogenesis of lung disease in both early and late stages through
      increased cytokine expression.

PMID- 8277181
TI  - Foscarnet-resistant herpes simplex virus infection in patients with AIDS.
AB  - Six human immunodeficiency virus-infected patients had clinical lesions of herpes
      simplex virus (HSV) type 2 that showed in vitro resistance to foscarnet. In each
      patient, lesions were unresponsive to foscarnet therapy or developed during daily
      suppressive foscarnet. Five patients had a history of intermittent or chronic
      foscarnet use for the management of acyclovir-resistant HSV infection, and 1 was
      receiving daily foscarnet for suppression of cytomegalovirus retinitis. Seven of
      10 foscarnet-resistant isolates from 6 patients were susceptible to acyclovir in
      vitro, and 1 was of borderline susceptibility. In 3 patients, the administration
      of acyclovir, either alone or in combination with foscarnet, resulted in healing.
      Clinically significant resistance to foscarnet may occur in immunosuppressed
      patients with prior foscarnet exposure. Addition or substitution of acyclovir to
      foscarnet therapy may be a useful strategy for patients in whom foscarnet
      resistance is suspected, pending the results of in vitro susceptibility testing.

PMID- 8277182
TI  - Persistence of cell-mediated and humoral immune responses in healthy children
      immunized with live attenuated varicella vaccine.
AB  - Two hundred fourteen healthy seronegative children immunized with various doses
      of Oka/Merck varicella vaccine were studied for persistence of varicella-zoster
      virus (VZV)-specific lymphocyte proliferation and antibodies to VZV as determined
      by a glycoprotein (gp) ELISA. Of the 140 vaccinees tested for VZV-specific
      lymphocyte proliferation, 94% had positive responses, with a mean stimulation
      index of 8.9 (range, 3.0-44.6). Of 214 tested by gpELISA, 95% were positive for
      up to 6 years after immunization; the geometric mean titer was 30.2 (range, 1.3
      3510.0). Of 122 individuals tested both by ELISA and for VZV-specific lymphocyte
      proliferation, 91% had persistence of both responses. Persistence of cellular and
      humoral immune responses in a large percentage of vaccinees for up to 6 years
      after immunization with Oka/Merck varicella vaccine suggests that protection
      against severe varicella is likely to be similarly long-lasting.

PMID- 8277183
TI  - Primary influenza A virus infection induces cross-reactive antibodies that
      enhance uptake of virus into Fc receptor-bearing cells.
AB  - Sera of young children who had had a primary infection with influenza A virus or
      were immunized with a live attenuated influenza A virus vaccine were examined for
      antibody responses that neutralized virus or enhanced uptake of virus into Fc
      receptor-bearing cells, because antibodies that enhance uptake of influenza virus
      into Fc receptor-bearing cells have been reported using mouse immune serum and
      monoclonal antibodies. The neutralizing antibody titers to the homologous
      infecting virus and to another H1N1 virus isolated several years later were
      higher after natural infection than after infection with the live attenuated
      virus. Natural infection and the attenuated vaccine induced antibodies that
      enhanced uptake of homologous virus and H1N1 virus isolated several years later.
      These results demonstrate that primary influenza A virus infection results in the
      induction of infection-enhancing antibodies.

PMID- 8277184
TI  - Community-wide outbreak of hemolytic-uremic syndrome associated with non-O157
      verocytotoxin-producing Escherichia coli.
AB  - From 20 April through 13 May 1992, 9 children were hospitalized with hemolytic
      uremic syndrome in Lombardia, Italy, where only 14 cases of this syndrome had
      occurred in the preceding 4 years. Cases were scattered in a large area
      encompassing five provinces, and the source of the outbreak was not identified.
      Eight patients needed dialysis, and there was 1 death. Seven of the 9 cases were
      examined for evidence of infection by Vero cytotoxin (VT)-producing Escherichia
      coli (VTEC). Six children had serum antibodies to the lipopolysaccharide of E.
      coli O111, and a VT-producing E. coli O111:NM was isolated from stool in 1 case.
      This is the first outbreak of VTEC infection recognized in Italy and the first
      associated with an E. coli serotype other than O157:H7.

PMID- 8277185
TI  - Serotypes responsible for invasive Streptococcus pneumoniae infections among
      children in Connecticut.
AB  - Active prospective surveillance to identify the serotypes of Streptococcus
      pneumoniae responsible for invasive infections among children in Connecticut was
      conducted from July 1984 through March 1993. S. pneumoniae isolates (722)
      recovered from normally sterile sites (98% from blood, 7% from both blood and
      cerebrospinal fluid) were serotyped by the Quellung reaction; 70% of the isolates
      were from children < 2 years old. Serotype 14 caused 29% of the infections. Seven
      serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) were responsible for 84% of the
      invasive infections overall and for 86% of the invasive infections among children
      < 2 years old. Formulations of polysaccharide-protein conjugate pneumococcal
      vaccines designed to prevent invasive infections in children in the United States
      should include these commonly isolated serotypes.

PMID- 8277186
TI  - Clinical safety, tolerability, and pharmacokinetics of murine monoclonal antibody
      to human tumor necrosis factor-alpha.
AB  - The safety, tolerability, and pharmacokinetic profile of murine monoclonal
      antibody to human tumor necrosis factor-alpha (TNF alpha MAb) were evaluated in
      20 uninfected patients at risk of sepsis and 16 septic patients. TNF alpha MAb
      was well tolerated in all patients, with no immediate or delayed signs of
      allergic reaction. During the 28-day evaluation, side effects included
      thrombocytosis (11), hepatic enzyme elevations (8), cardiac arrhythmias (3), and
      deaths (5). Each was attributed to the patient's severe underlying disease and
      not to TNF alpha MAb; however, a relationship between TNF alpha MAb and these
      events cannot be ruled out. The half-life was 52 h for a single infusion of TNF
      alpha MAb. Human antibody against TNF alpha MAb was observed in 13 (76.5%) of 17
      phase IA patients and 10 of 10 phase IB patients and anti-idiotype antibodies in
      11 (91.7%) of 12 phase IA patients and 2 (33.3%) of 6 phase IB patients. TNF
      alpha MAb should be evaluated as adjunctive therapy for patients with sepsis.

PMID- 8277187
TI  - The intestinal elimination of ciprofloxacin in the rat.
AB  - The transepithelial intestinal elimination of ciprofloxacin was studied in a rat
      model. Two jejunal and one ileal segment, along with their intact blood supplies,
      were isolated and continuously perfused. Following a single parenteral
      administration of 25 mg/kg ciprofloxacin, the drug in amounts of 1.97 +/- 0.70,
      1.88 +/- 0.99, and 1.44 +/- 0.77 micrograms/cm2 of mucosal surface was recovered
      over 90 min from the proximal and distal jejunal loops and the ileal loop,
      respectively, reaching a calculated fraction of 6%-7% of the dose eliminated in
      the entire small intestine. The rate of intestinal elimination related linearly
      to the parenteral dose. In the proximal jejunum, however, doses > 25 mg/kg were
      not accompanied by a concomitant increase in the eliminated fraction, suggesting
      a saturable transport process. Parenterally administered probenecid, amoxicillin,
      and nifedipine and changes ranging from 6.0 to 8.5 in the pH of the perfusates
      did not alter transepithelial elimination. This pathway of elimination of
      ciprofloxacin may play an important role in curing intestinal infections.

PMID- 8277188
TI  - Cytomegalovirus is present in semen from a population of men seeking fertility
      evaluation.

PMID- 8277189
TI  - Low human T cell leukemia virus type II seroprevalence in Africa.

PMID- 8277190
TI  - A serologic analysis and the amino acid sequence of the V3 region of human
      immunodeficiency virus from carriers in Bangkok.

PMID- 8277191
TI  - Control of a hepatitis A outbreak by active immunization of high-risk susceptible
      subjects.

PMID- 8277192
TI  - Hepatitis E virus and posttransfusion hepatitis.

PMID- 8277193
TI  - Lack of cross-protection against diarrhea due to Vibrio cholerae O139 (Bengal
      strain) after oral immunization of rabbits with V. cholerae O1 vaccine strain
      CVD103-HgR.

PMID- 8277194
TI  - The effect of deferoxamine on different zygomycetes.

PMID- 8277195
TI  - The effects of high-dose recombinant soluble CD4 on human immunodeficiency virus
      type 1 viremia.
AB  - In vitro, low-passage clinical human immunodeficiency virus type 1 (HIV-1)
      isolates require up to 1000 times greater serum levels of recombinant soluble CD4
      (rsCD4) than have ever been given. To determine if sufficient serum levels of
      rsCD4 provide in vivo inhibition of HIV-1, 4 HIV-1 plasma-viremic subjects were
      given single-dose boluses of 2, 4, 6, 8, and 10 mg/kg intravenous rsCD4. Plasma
      HIV-1 cultures were done after infusion. Three subjects demonstrated a dose
      dependent reduction in plasma HIV-1 viremia. The inhibitory effect of rsCD4 on
      plasma HIV-1 viremia was associated with the in vitro ID90-95 of the isolate, not
      the ID50. These data demonstrate that extremely high doses of rsCD4 inactivate
      cell-free HIV-1 in vivo and suggest that high doses of rsCD4 may have some short
      term therapeutic utility, such as with accidental or occupational HIV-1 exposure.

PMID- 8277196
TI  - Immune responses elicited by recombinant vaccinia-human immunodeficiency virus
      (HIV) envelope and HIV envelope protein: analysis of the durability of responses
      and effect of repeated boosting.
AB  - Previous studies indicate that immunization with recombinant (r) vaccinia-human
      immunodeficiency virus type 1 (HIV-1) gp160 and boosting with baculovirus-derived
      HIV-1 rgp160 results in stronger cellular and antibody responses than those
      following either vaccine alone. The durability of immunity over 1 year was
      evaluated in 12 recipients. Both cellular and binding antibody responses remained
      detectable but diminished, and neutralizing antibodies were absent. To boost
      immunity, rgp160 was given again 1 year after the initial boost. Reboosting
      elicited strong HIV-specific lymphoproliferative responses. Binding antibody
      levels also rose dramatically, and the magnitude of the peak responses was
      significantly greater following the 2-year than following the 1-year boost.
      However, neutralizing antibody titers were low (1:10-1:20) and detected in only 4
      of 12 persons. Moreover, persistent CD8+ cytolytic responses were not induced.
      Thus, although repeated rgp160 boosting after vaccinia-envelope priming can
      augment selected immune components, an altered regimen may be necessary to
      achieve protective long-term immunity to HIV-1.

PMID- 8277197
TI  - Two antigenically distinct subtypes of human immunodeficiency virus type 1: viral
      genotype predicts neutralization serotype.
AB  - At least five distinct genetic subtypes (genotypes) of human immunodeficiency
      virus type 1 (HIV-1) have been identified by DNA sequencing. Current vaccine
      candidates are based on virus strains from North America and Europe that
      represent only one subtype. The extent to which distinct genotypes of HIV-1
      correspond to antigenically distinguishable serotypes is largely unknown and may
      be critically important to vaccine design. Cross-neuralization studies were done
      with viruses and plasma from two different genotypes. Based on neutralization
      susceptibility, 10 primary HIV-1 isolates from Thailand and the United States
      were classified into one of two antigenic subtypes that correlated with viral
      genotype. The existence of serotypes of HIV-1 suggests that a broadly effective
      vaccine may have to include strains from multiple subtypes. Neutralization of
      these primary HIV-1 isolates differed substantially from results with laboratory
      strains. Future neutralization studies using primary isolates and multiple
      genotypes may be important for assessment of HIV-1 antigenic diversity.

PMID- 8277198
TI  - Enhanced endocytosis and anti-human immunodeficiency virus type 1 activity of
      anti-rev antibodies after cationization.
AB  - Transmembrane transport and endocytosis of antibodies is facilitated by
      cationization, when the isoelectric point of the antibody is raised to the
      cationic range. The present studies describe the preparation of affinity-purified
      polyclonal antibodies directed against a 16-amino acid synthetic peptide
      corresponding to amino acids 35-50 of the 116-amino acid rev protein of human
      immunodeficiency virus type 1 (HIV-1). The concentration of cationized anti-rev35
      50 antibody that results in 50% binding to the rev epitope, based on results with
      an immunoradiometric assay, also results in a statistically significant 37%
      inhibition of HIV-1 replication in human peripheral blood lymphocytes. The
      cationized antibodies caused no measurable toxicity to the cells, on the basis of
      [3H]thymidine incorporation. These studies demonstrate that cationization results
      in enhanced endocytosis of the antibody and enhanced inhibition of HIV-1
      replication, consistent with intracellular immunization of the rev protein.

PMID- 8277199
TI  - Transmission of hepatitis B virus analyzed by conformation-dependent
      polymorphisms of single-stranded viral DNA.
AB  - Hepatitis B virus (HBV) DNA from regions coding for surface and core antigens
      were amplified and radiolabeled from hepatitis B surface antigen (HBsAg)-positive
      serum samples by polymerase chain reaction, heat-denatured, and analyzed for
      conformation-dependent polymorphisms by gel electrophoresis under nondenaturation
      conditions. Analysis of serum samples representative of diverse and identical
      HBsAg subtypes showed a wide range of autoradiographic banding patterns, each
      unique to the specimen. Serial samples of a long-term carrier showed relative
      stability of banding patterns over time. Epidemiologic analyses using this
      procedure showed banding patterns of case subjects to be identical to those of
      persons implicated as the source. This facile and discriminatory approach to the
      differentiation of viral strains should be useful in the study of HBV
      transmission.

PMID- 8277200
TI  - A randomized controlled trial of cold-adapted and inactivated vaccines for the
      prevention of influenza A disease.
AB  - A double-blind, randomized controlled trial over 5 years compared the safety,
      immunogenicity, and efficacy of cold-adapted and inactivated influenza A vaccines
      in 5210 normal subjects. Both vaccines were well tolerated. Inactivated vaccine
      significantly increased hemagglutination inhibition antibody titers. Significant
      titer rises were also noted after cold-adapted vaccine but of lesser magnitude
      than with inactivated vaccine. The efficacy of inactivated vaccine in preventing
      culture-positive influenza was 76% (95% confidence interval [CI], 58%-87%) for
      H1N1 disease and 74% (95% CI, 52%-86%) for H3N2; for cold-adapted vaccine, 85%
      (95% CI, 70%-92%) and 58% (95% CI, 29%-75%), respectively. The efficacy of
      inactivated vaccine in preventing a four-fold rise in antibody titer over the
      influenza season was 69% (95% CI, 61%-76%) for H1N1 and 73% (95% CI, 65%-79%) for
      H3N2; for cold-adapted vaccine, 54% (95% CI, 44%-62%) and 32% (95% CI, 17%-44%),
      respectively. Cold-adapted and inactivated influenza vaccines are safe and
      effective for preventing influenza A disease.

PMID- 8277201
TI  - Sustained transmission of mumps in a highly vaccinated population: assessment of
      primary vaccine failure and waning vaccine-induced immunity.
AB  - From January to July 1991, an outbreak of mumps occurred in Maury County,
      Tennessee. At the primarily affected high school, where 98% of students and all
      but 1 student with mumps had been vaccinated before the outbreak, 68 mumps cases
      occurred among 1116 students (attack rate, 6.1%). Students vaccinated before 1988
      (the first year mumps vaccination was required for school attendance in
      Tennessee) may have been at greater risk of mumps than those vaccinated later
      (65[6.1%] of 1001 vs. 2[2.2%] of 89; risk ratio, 2.9; 95% confidence interval,
      0.7-11.6). Of 13 persons with confirmed mumps who underwent serologic testing, 3
      lacked IgM antibody in well-timed acute- and convalescent-phase serum specimens.
      Vaccine failure accounted for a sustained mumps outbreak in a highly vaccinated
      population. Most mumps cases were attributable to primary vaccine failure. It is
      possible that waning vaccine-induced immunity also played a role.

PMID- 8277202
TI  - Detection of varicella-zoster virus DNA in air samples from hospital rooms.
AB  - Varicella-zoster virus (VZV) is a highly contagious infectious agent that causes
      outbreaks in institutional settings. Transmission of VZV is felt to occur
      following direct contact with an infected individual and by aerosol spread. To
      document the aerosolization of VZV, a polymerase chain reaction (PCR) assay was
      used to detect VZV DNA in air samples obtained from hospital rooms of patients
      with active VZV infection. VZV DNA was detected in 64 (82%) of 78 air samples
      from rooms housing patients with active varicella and 9(70%) of 13 samples from
      rooms of patients with herpes zoster. VZV was detected 1.2-5.5 m from patients'
      beds and for 1-6 days following onset of rash. On some occasions, VZV DNA could
      be detected outside the hospital isolation rooms housing patients. This PCR-based
      method allows the detection and semiquantitation of VZV aerosolization and can be
      a useful tool for monitoring efforts to control VZV aerosols in the environment.

PMID- 8277204
TI  - Conventional antibodies: requirements and methods for their optimization.
AB  - Eighteen years after the discovery of monoclonal antibodies (MAbs), the debate as
      to whether these reagents have fulfilled their promise must now be addressed.
      When MAbs were studied as tools for diagnosis and therapy, problems arose
      regarding the reagents themselves and the recognized target antigens. Because
      most MAbs are of murine origin, they usually evoke an immune response in human
      patients, which reduces their effectiveness. Moreover, their bulky size and
      dispersal via the blood prevent most of the injected antibodies from
      substantially penetrating solid, poorly vascularized tumors. However, MAbs that
      are adequately selected and manipulated to circumvent these problems have been
      found to successfully image tumors and to be therapeutically active.

PMID- 8277203
TI  - Cellular distribution of endotoxin after injection of chemically purified
      lipopolysaccharide differs from that after injection of live bacteria.
AB  - Lipopolysaccharide (LPS) chemically extracted from gram-negative bacteria is
      often used in animal models to study endotoxemia. Laser confocal microscopy and
      immunofluorescence staining for comparison of injections of live Escherichia coli
      O111:B4 bacteria with LPS extracted from the same strain showed that cellular
      localization and time course in rat organs were markedly different after the two
      injections. Fluorescent staining and image analysis software allowed quantitative
      comparison of LPS within tissues at different times and doses. Antigenic LPS was
      detected in all tissues 1 hour after injection of both bacteria and LPS and was
      present in liver and spleen over the 28-day study period. Whole bacteria were
      identified in tissue macrophages for the first 48 h after injection; later,
      bacterial cell walls were replaced by diffuse antigenic material throughout the
      cytoplasm. Antigenic LPS was localized within hepatocytes only after injection of
      chemically purified LPS. Cellular localization of LPS in tissues is dependent on
      the form injected. Animal models that use purified LPS may not be representative
      of gram-negative bacteremia.

PMID- 8277205
TI  - Monoclonal antibodies by genetic engineering: novel reagents for in vivo
      diagnosis and therapy.
AB  - In only a few years, the technology of antibody engineering has demonstrated its
      power and a variety of recombinant monoclonal antibodies are now being developed.
      Recent developments in gene manipulation have allowed the isolation of
      antibodies, including human antibodies, with or without immunization, by
      displaying functional antibody fragments on the surface of bacteriophage
      particles and directly selecting with antigen. In the present review some recent
      achievements in these areas are highlighted.

PMID- 8277206
TI  - The role of cytokines in the modulation of cell surface antigens of human
      melanoma.
AB  - A number of different cytokines, including IL-1 alpha and beta, IL-2, IL-3, IL-4,
      IL-6, IL-7, IL-8, IFN-alpha, -beta and gamma, TNF-alpha -beta, and TGF-beta 1,
      can modulate the expression of distinct cell surface antigens of normal and
      neoplastic cells. Both induction/increase of expression and reduction of
      expression can be achieved depending on the antigen and on the cytokine. Antigens
      subjected to the modulating activity of cytokines include distinct families of
      cell surface structures such as the molecules coded by the major
      histocompatibility complex (MHC), the superfamily of adhesion receptors that
      regulate cell-cell and cell-matrix interaction, receptors for cytokines and
      growth factors and tumor-associated antigens. The modulating activity of
      cytokines is a consequence of their influence on gene expression, protein
      synthesis, membrane expression and shedding of antigens from the cell surface.
      The changes of phenotype due to the action of cytokines can influence the
      signalling pathways dependent on the expression and function of cell surface
      structures. Therefore, the antigen modulating activity of cytokines can
      thoroughly affect the biological behavior of normal and neoplastic cells. As
      described here, most of the modulating effects of cytokines on different cell
      surface structures and the functional consequences of antigenic modulation can be
      verified in human malignant melanoma cells.

PMID- 8277207
TI  - Pretargeting of carcinomas with the avidin-biotin system.
AB  - Diagnosis and experimental therapy of cancer have been performed with encouraging
      results using radiolabelled monoclonal antibodies. However, the high background
      due to non-specific uptake by normal tissue and blood is a major drawback in
      antibody-guided tumor detection. Various strategies have been proposed to
      overcome this problem, such as computed background subtraction, use of a second
      antibody, and local delivery. An antibody is a slow "bullet" for tumor targeting,
      since in many lesions it requires two or three days to accumulate. The use of
      fragments such as F(ab')2 or Fab, which display a faster blood clearance than
      whole antibody, improves tumor localization to a sufficient extent (hours) to
      allow the use of the most suitable radionuclides, e.g. 99m-Tc. In therapeutic
      applications we are still far away from the optimal condition in terms of the
      absolute amount of radioactivity delivered to the tumor. The high specificity of
      antibodies could be exploited at its best by delaying the delivery of the label
      to a time when the ratio tumor-bound to non-tumor-bound antibody has reached its
      maximum value. To obtain this goal, the label should display a fast clearance and
      should be captured by the antibody already targeted onto tumor cells. These
      considerations have led to strategies of tumor pretargeting where antibody and
      label are administered separately. One of these strategies, based on the avidin
      biotin system, has already been used extensively for several years in
      immunohistochemistry and in ELISA. Due to the flexibility of this system, several
      alternative protocols are possible.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277208
TI  - Intraoperative radioimmunolocalization of colorectal cancer: a review.
AB  - Although intraoperative radioimmunolocalization (IORIL) is gaining wider
      acceptance, several limits inhibit a more extensive clinical use. In this paper
      the following topics will be discussed: 1) the clinical approach, that is, the
      combined use of immunoscintigraphy and IORIL after a single MAb administration or
      the use of non-imaging 125 I MAb; 2) the detector type and its collimation and
      shielding; 3) the nuclides employed, and 4) the background problem. The clinical
      results of our and other groups show a sensitivity that is generally higher than
      0.75 with a high positive predictive value. The detection rate of occult lesions
      is in the order of 20% of all explored sites. However, the current state of
      detector and MAb technology do not allow to achieve better results; probably the
      results can be improved by the use of bispecific MAb or the avidin-biotin system.

PMID- 8277209
TI  - Radionuclide therapy of tumors: general aspects and considerations.
AB  - Therapeutic nuclear medicine is rapidly developing as an additional treatment
      modality in oncology. Its unique characteristics are the systemic, yet selective
      delivery of radiation doses in target tissues, its non-invasiveness, the relative
      lack of immediate and late side effects, and the advantage that uptake and
      retention in the tumor can be pre-assessed by tracer studies. Many different
      tumor seeking radiopharmaceuticals are being used for therapy by different routes
      and a variety of targeting mechanisms. The current clinical role of radionuclide
      therapy is briefly reviewed, as well as more general aspects and considerations,
      such as mechanisms for tumor targeting, the choice of radionuclide labels,
      radiopharmacy, drug delivery, radiation protection, dosimetry and toxicity.

PMID- 8277210
TI  - Radionuclides for radioimmunotherapy: criteria for selection.
AB  - In developing and designing radioimmunotherapy, the selection of the isotope is a
      major factor. This selection depends on a number of criteria and parameters,
      affecting usefulness and feasibility. Usefulness is directly related to the
      radiological performance of the ionising radiation in relation to tissue and its
      morphology, with a major distinction between the effects of alpha and beta
      particles (or rays). Usefulness is also directly related to the pharmacodynamic
      performance of the isotope-carrier (e.g. antibody) complex, where the proper
      choice of isotope radiodecay halflife is of major importance. Feasibility depends
      on availability of the components in the isotope-ligand-carrier complex, and also
      on convenience and safety aspects in the preparation and the handling of the
      materials as well as in their application in patients. A comparison is made
      between the various properties of alpha-emitting isotopes that have been proposed
      over a number of years, concluding that the combination 225Ac- 213Bi deserves
      serious further attention.

PMID- 8277211
TI  - Radioimmunotherapy of ovarian cancer.
AB  - Radioimmunotherapy (RIT) is a new therapeutical approach where radiolabeled
      monoclonal antibodies (MAb) against tumor-associated antigens are administered to
      treat tumor lesions. Ovarian cancer is one of the most promising fields for RIT.
      This paper gives an overview of some biodistribution studies in animal models and
      in patients with radiolabeled anti-ovarian cancer MAbs, and defines the main
      criteria which should be considered to plan a clinical trial of RIT in ovarian
      cancer. As regards the clinical results, the published outcome of various trials
      and the experience of the National Cancer Institute of Milan are summarized. Even
      if the number of patients involved in these clinical studies of RIT is too small
      to provide conclusive indications about its role in the management of ovarian
      cancer, the preliminary results from qualified groups show its potential in this
      disease despite the current problems that limit clinical application (above all,
      the instability of the radiolabeled linkage, the immunogenicity of murine
      antibodies, the poor absolute tumor radiolabel uptake and the bone marrow
      toxicity).

PMID- 8277212
TI  - Radioimmunotherapy of gastrointestinal cancer and glioblastomas.
AB  - Two groups of patients with gastro-intestinal (GI) tumours (41) and recurrent
      glioblastoma (GBM), (17) underwent radioimmunotherapy after the failure of
      traditional treatments. A number of different MAbs were employed (anti-CEA and
      anti-Tenascin) which were labelled with I-131. The radiopharmaceuticals were
      administered by the intraperitoneal and intratumoral routes. As a rule the cycles
      were repeated to enhance the effectiveness of RIT. No significant early or late
      adverse effects were recorded. HAMA development was observed in all GI cases but
      only in a few GBM patients. The cumulative dose delivered to the target tumors
      was considerable (mean 8,900 cGy) in the GI group, and was much higher in the GBM
      patients (mean 51,700 cGy) owing to the particular modality of injection.
      Survival improved in both series of patients. The objective responses to RIT were
      promising: in the GI group 10 complete remissions (CR) and 6 partial remissions
      (PR) were observed, while in the GBM group 3 long-lasting CRs and 3 prolonged PRs
      were documented.

PMID- 8277213
TI  - Behaviour of four serum tumor markers in pregnant women.

PMID- 8277214
TI  - [The 46th General Meeting of the Japanese Association for Thoracic Surgery.
      Sapporo, Hokkaido. October 5-7, 1993. Abstracts].

PMID- 8277215
TI  - Post-transcriptional regulation of hormone synthesis.

PMID- 8277216
TI  - Effects of phorbol ester on protein kinase C activity and effects of depletion of
      its activity on thyrotrophin, forskolin and 8'-bromoadenosine 3',5'-cyclic
      monophosphate-induced [3H]thymidine incorporation in rat FRTL-5 cells.
AB  - Protein kinase C (PKC) activity was measured in rat FRTL-5 cells cultured in
      medium containing insulin and transferrin (2H medium), in cells treated with
      phorbol 12,13-dibutyrate (PDBu), an activator of PKC, and in cells treated with 4
      alpha-12,13-phorbol didecanoate (4 alpha-PDD), an inactive phorbol ester, in
      order to study the translocation and down-regulation of its activity. Provided
      the PDBu induced translocation and down-regulation of PKC activity, we used the
      down-regulated cells to study the roles played by PKC in DNA synthesis induced by
      stimuli which increase cyclic AMP (cAMP) and a cAMP analogue. Cytosolic
      preparations obtained from cells cultured in 2H media were fractionated on a DEAE
      cellulose column, and fractions were assayed for PKC activity. PKC activity was
      eluted at concentrations between 0.06 and 0.15 mol NaCl/l with a peak at 0.1
      mol/l. Exposure of cells to PDBu (100 ng/ml) resulted in 53% loss of initial PKC
      activity in the cytosolic fraction in concert with reciprocal augmentation of PKC
      activity in the particulate fraction that peaked at 321% of the initial level at
      15 min of exposure. When cells were stimulated with 100 ng PDBu/ml for 15 min,
      three- and 1.9-fold greater PKC activity appeared in the particular and total
      cellular (cytosol plus particulate) fractions respectively than was the case for
      stimulation with 10 ng PDBu/ml. The total cellular PKC activity transiently
      increased at 15 min to 137% and subsequently decreased to 74, 40 and 25% of the
      initial level at 1, 12 and 24 h respectively. However, translocation of PKC
      activity to the particulate fraction was not observed in cells treated for 15 min
      with either 10 or 100 ng 4 alpha-PDD/ml and total cellular PKC activity was
      modestly reduced, to 97% of the initial level in cells exposed to 4 alpha-PDD
      (100 ng/ml) for 24 h. [3H]Thymidine incorporation was measured in cells whose PKC
      activity was stimulated by TSH, forskolin or 8-bromoadenosine cAMP simultaneously
      with PDBu (100 ng/ml), and also in cells whose PKC activity had been down
      regulated by pretreatment with PDBu prior to the addition of each stimulant. The
      [3H]thymidine incorporation induced by each of the stimulants was inhibited in
      cells whose PKC activity was subjected to simultaneous stimulation, but was
      enhanced in cells whose PKC activity had previously been depleted. This
      potentiating effect of PDBu pretreatment on subsequent TSH-induced [3H]thymidine
      incorporation was not observed in cells exposed to PDBu for less than 12 h, but
      was observed in cells exposed for 24 h or longer.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8277217
TI  - The involvement of vasopressin in the renal actions of atrial natriuretic peptide
      in conscious fluid-balanced rats.
AB  - The renal and endocrine actions of atrial natriuretic peptide (ANP) administered
      at a rate to induce plasma concentrations within the physiological range have
      been re-examined in conscious rats in which body fluid volume was maintained by
      infusion of replacement fluid at a rate to match spontaneous urine losses (servo
      controlled replacement) throughout experimentation. The involvement of
      vasopressin in the actions of ANP was assessed by comparing the responses induced
      in Brattleboro (DI) and Long-Evans (LE) rats. A rate of ANP administration
      inducing a less than twofold increment in circulating ANP concentration evoked a
      small but significant diuresis and natriuresis. In contrast to previous studies
      during which body fluid balance had not been maintained and the response to ANP
      was transient, renal responses were rapid in onset and sustained over the period
      of hormone administration. The change in renal excretion occurred without
      concomitant changes in mean arterial blood pressure, haematocrit or glomerular
      filtration rate, and without consistent alterations in the circulating
      concentrations of angiotensin II, vasopressin, aldosterone or corticosterone.
      Furthermore, although small differences between the two strains in the character
      of the response could be demonstrated, the evoked response was of similar
      magnitude in vasopressin-replete and -deficient animals. In summary, in conscious
      rats in which body fluid volume was maintained, the profile of the diuretic and
      natriuretic responses evoked by low-rate ANP administration was different from
      that previously observed in anaesthetized and/or constantly infused preparations;
      being rapid in onset and sustained.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277218
TI  - The uterine growth-promoting action of epidermal growth factor and its function
      in the fertility of mice.
AB  - Epidermal growth factor (EGF) levels in the submandibular glands and plasma are
      increased in pregnant and aged female mice. The possible role of EGF in fertility
      was studied in virgin and pregnant mice ranging in age from 10 to 90 weeks of
      age, employing sialoadenectomy, administration of EGF antibody and EGF
      replacement. The uterine weight in pregnant, 10-week-old, sialoadenectomized mice
      was significantly less than in normal mice and the administration of EGF antibody
      to these mice further decreased uterine weight, resulting in an increased rate of
      abortion. Replacement EGF treatment in the sialoadenectomized mice prevented
      these changes. Uterine weight was about 70 mg at 10 weeks of age, and
      significantly increased from 30 to 80 weeks when it reached a plateau level of
      275 mg. These changes closely followed the increase in the concentration of EGF
      in the submandibular glands and plasma and coincided with the decline in
      fertility. In contrast, uterine weight in the sialoadenectomized mice decreased
      immediately after the operation and remained at about 50-60 mg throughout the
      experimental period. Pregnancy, as judged by implantation, was achieved in the
      sialoadenectomized mice at later ages than in the controls. These findings
      suggest that elevated EGF levels may have a dual function in the control of
      fertility via uterine growth, depending on the age of mice.

PMID- 8277219
TI  - Renal melatonin excretion in sheep is enhanced by water diuresis.
AB  - Diurnal variation in blood melatonin levels and renal melatonin excretion was
      monitored in five ewes by blood sampling and quantitative urine collection at 2-h
      intervals. A typical secretory pattern of melatonin was seen both in blood and
      urine levels and in the renal excretion of melatonin. Serum melatonin levels
      increased from daytime values of approximately 200 pmol/l to a mean of 800 pmol/l
      during darkness. Urine flow rate and urine osmolality did not show any clear
      diurnal rhythm. To examine whether urine flow rate affects renal melatonin
      excretion at night, urine was collected in three consecutive 30-min fractions,
      and blood was sampled in the middle of each urine collection period when the
      sheep were in normal water balance or after hydration. Hydration increased urine
      flow rate over sixfold and decreased urine osmolality well below plasma
      osmolality. Glomerular filtration rate, measured as creatinine clearance, did not
      change. Serum melatonin concentrations did not differ between hydrated and non
      hydrated sheep. However, urinary melatonin excretion was 1.1 +/- 0.3 (S.E.M.)
      pmol/min at midnight in normal water balance, and significantly higher (2.6 +/-
      0.4 pmol/min) in the hydrated state. In this study, the validity of urinary
      melatonin determinations as an indicator of pineal function was confirmed in
      normal water balance. In addition, our results suggest that a high tubular fluid
      load during diuresis increases urinary melatonin excretion because of decreased
      tubular reabsorption.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277220
TI  - Clearance of exogenous parathyroid hormone-related protein in pregnant, non
      pregnant and fetal sheep, goats and pigs.
AB  - In the sheep, goat and pig, radiolabelled parathyroid hormone related protein
      (PTHRP) and immunoreactive PTHRP(1-34) and (1-86) were rapidly cleared from the
      circulation. Metabolic clearance rates (MCR) were in the range of 1.25-7.5 ml/min
      per kg and were slightly slower than that of intact PTH in man (10 ml/min per
      kg); while the mean MCR of labelled PTHRP(1-86) in fetal sheep and goats was
      significantly faster than that in their respective mothers (14.4 vs 4.0 ml/min
      per kg respectively). This may reflect increased metabolism of PTHRP by fetal
      tissues, e.g. the placenta. Similar rates of clearance of radiolabelled PTHRP(1
      141), (1-86) and (1-34) suggest that clearance involves the amino terminus of the
      molecule.

PMID- 8277221
TI  - Localization of oestradiol, progesterone and oxytocin receptors in the uterus
      during the oestrous cycle and early pregnancy of the ewe.
AB  - Uterine tissue samples were collected from 47 ewes at various stages of the
      oestrous cycle and early pregnancy (until day 21) and during seasonal anoestrus.
      Cryostat sections were immunostained to determine the localization of oestradiol
      and progesterone receptors using specific monoclonal antibodies. Oxytocin
      receptors were localized by autoradiography in sections from the same ewes using
      the 125I-labelled oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]-
      vasotocin. Plasma progesterone measurements were made during the preceding cycle
      up to the time of slaughter. Oestradiol receptor concentrations were maximal in
      all regions of the tract at oestrus. Immunostaining of the luminal epithelium,
      superficial glandular epithelium, stroma and myometrium decreased in the early
      luteal phase but was maintained for longer in the deep glands. Progesterone
      receptor immunostaining in the luminal epithelium and superficial glands
      developed in the early luteal phase (days 1-2) with a somewhat later appearance
      in the deep glands (days 5-7). Progesterone receptor concentrations in the stroma
      and myometrium also reached a maximum in the early luteal phase. Myometrial
      staining was clearly maintained throughout the luteal phase whereas stromal
      staining was variable between ewes. For both oestradiol and progesterone
      receptors no differences were apparent between pregnant and non-pregnant ewes
      between days 2 and 12, but pregnant ewes did not show the general increases in
      oestradiol receptor staining associated with luteolysis on days 14-15. Oxytocin
      receptors first developed in the luminal epithelium of non-pregnant ewes on day
      14 of the cycle and spread to the superficial glands, caruncular stroma, deep
      glands and myometrium at oestrus before decreasing in reverse order on days 1-2.
      Specific binding was not detectable on days 5-12 of the cycle or on days 14 or 21
      of pregnancy. The appearance of oxytocin receptors in the luminal epithelium on
      day 14 preceded that of both the oestradiol and progesterone receptors in the
      epithelial cells and the fall in plasma progesterone. It was followed by the
      development of oestradiol and oxytocin receptors in the superficial glands, deep
      glands, caruncular stroma and myometrium, with the two receptor populations
      showing a significant positive association in these tissues. The loss of oxytocin
      receptors in all regions occurred as plasma progesterone levels were increasing,
      but the association between these two variables was only significant in the
      superficial glands. The development of progesterone receptors in different
      tissues could not be explained on the basis of either oestradiol receptor content
      or plasma progesterone.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8277222
TI  - Protein kinase in rat adipocytes: influence of androgenic status and regional fat
      distribution.
AB  - The effects of castration and testosterone treatment on insulin- and phorbol
      ester (TPA)-stimulated lipogenic responses, phorbol dibutyrate-specific binding
      to protein kinase C (PKC) in the cytosol and the beta-PKC isoform level
      quantified by immunoblotting were compared in rat fat cells from femoral
      subcutaneous (SC) and deep intra-abdominal (epididymal) fat deposits. In control
      rats, the PKC content was lower in SC than in epididymal fat cells. After
      castration, the difference in PKC content between SC and epididymal fat cells was
      reduced and restored by testosterone treatment. However, androgenic status failed
      to modify the PKC content in SC fat cells. The lipogenic response to insulin was
      also differently regulated by the androgenic status in the two fat deposits.
      After castration, the response was increased in SC fat cells, while it was
      blunted in epididymal fat cells. These effects were corrected by testosterone
      administration. These results demonstrate that, in white adipocytes, PKC is an
      additional biological parameter which varies according to the anatomical origin
      of the fat cells. They also provide evidence that PKC is controlled by androgens
      in vivo and emphasize the regional site specificity of such a control.

PMID- 8277223
TI  - The effect of tri-iodothyronine on the membrane potential and intracellular
      sodium and potassium activities of rat soleus and extensor digitorum longus
      muscles.
AB  - Tri-iodothyronine (T3) induces a considerable increase in the number of Na/K pump
      units in rat skeletal muscles, but this effect is more pronounced in red muscles,
      such as soleus, than in white muscles such as extensor digitorum longus (EDL). In
      the present study, the effect of T3 on the membrane potential (Em) and the
      intracellular activities of K+ and Na+ (aKi and aNai) in the two muscle types has
      been studied using microelectrodes. Hyperthyroidism was induced by seven
      subcutaneous injections of 50 micrograms T3 per 100 g body weight on alternate
      days. Following treatment of rats with T3, the mean T3 concentration in the serum
      was 8.4 +/- 0.46 nmol/l (S.D.) compared with 1.1 +/- 0.16 nmol/l in the serum of
      untreated control rats, and the heart weight/body weight ratio of the treated
      rats had increased from 0.29 +/- 0.01 in control rats to 0.39 +/- 0.02. In soleus
      muscle fibres from the T3-treated rats, the Em, aKi and aNai were unchanged,
      whereas, in EDL muscle fibres from these rats, the Em had depolarized by 2 mV (P
      < 0.01) and aNai had increased by 2 mmol/l (P < 0.05). Since T3 induces not only
      an increase in the number of pump units and active movement of Na+ and K+ but
      also an increase in the passive fluxes of these ions, the results are discussed
      in terms of these two opposing ionic movements.

PMID- 8277224
TI  - Plasma somatolactin concentrations in salmonid fish are elevated by stress.
AB  - The preliminary finding that plasma levels of somatolactin (SL) were markedly
      elevated following stress caused by confinement in chinook salmon (Oncorhynchus
      tshawytscha) prompted a more detailed study of SL dynamics during stress. SL
      levels have been determined in the plasma of rainbow trout (Oncorhynchus mykiss)
      during exposure to acute (0-30 min) and short (0-24 h) periods of stress
      resulting from handling and confinement. The results show that SL levels increase
      rapidly within minutes following the onset of stress, reach a peak between 1 and
      2 h, decline over the next 3 h, and then show an additional increase again by 24
      h. During acute stress caused by confinement, the increase in plasma SL levels
      occurred within 2 min, thus showing a more rapid response than cortisol. This
      suggests that the response is mediated directly by the hypothalamus and is not a
      result of a feedback mechanism. The results also demonstrate that SL secretion in
      response to stress is at least partially under genetic control. In the short-term
      stress experiment, progeny of fish selected as high responders or low responders
      to stress, based on the magnitude of the plasma cortisol levels induced by
      stress, were used, and these fish showed similarly accentuated or attenuated
      release of SL following stress. These results clearly demonstrate that non
      specific environmental stress causes rapid activation of SL-secreting cells in
      the pars intermedia, suggesting that this hormone has an important role in the
      adaptive response of fish to stress.

PMID- 8277225
TI  - Tumour necrosis factor-alpha modulates oestradiol responsiveness of MCF-7 breast
      cancer cells in vitro.
AB  - We studied the effect of tumour necrosis factor-alpha (TNF) on oestradiol
      regulation of growth and metabolism of MCF-7 breast cancer cells to determine
      whether TNF altered the oestradiol responsiveness of these cells. We found that
      TNF antagonized oestradiol stimulation of cell growth in a dose-dependent manner,
      with partial inhibition at 1.0 U/ml and complete inhibition at 1000 U/ml. TNF
      inhibited cell cycle progression, increasing cells in the G0G1 phase and blocking
      oestradiol-stimulated progression into the S phase. We examined the effect of TNF
      on three oestrogen-regulated proteins, the oestrogen receptor (ER), the
      progesterone receptor (PR) and insulin-like growth factor-I (IGF-I). TNF down
      regulated the ER and up-regulated the PR. Both of these processes were enhanced
      by the addition of oestradiol. The effects of TNF on the ER and PR were dose
      dependent and occurred without a change in the Kd of the receptor. TNF did not
      change the respective steady-state mRNA levels. In addition, TNF did not alter
      secretion of IGF-I either in the absence or presence of oestradiol, indicating
      that the effects of TNF on oestrogen-regulated proteins in selective. These
      findings indicate an important interaction between the immune and endocrine
      systems. The cytokine TNF has a prominent effect on oestradiol stimulation of MCF
      7 cells, blocking its proliferative response and enhancing certain metabolic
      effects. These actions may be mediated in part through modulation of the ER,
      although other pathways appear to be involved.

PMID- 8277226
TI  - Isolation and characterization of human LH isoforms.
AB  - Thirty-nine human LH (hLH) isoforms were chromatographically separated from human
      pituitary extracts using a mild purification procedure which consisted of
      preparative isoelectric focusing, high-performance ion-exchange chromatography
      and immobilized metal-affinity chromatography. Twenty of these hLH isoforms were
      characterized by LH radioreceptor assay, SDS-PAGE and amino acid analysis, and 17
      were shown to be highly purified (> 90% pure). The specific activities of these
      hLH isoforms ranged from 1980 to 38,650 IU/mg protein in terms of the 2nd IS for
      human pituitary LH, based on protein content as determined by amino acid
      analysis. hFSH and hTSH content were < 0.5% and < 7.8% respectively. The purity
      was assessed by silver staining on SDS-PAGE. Under non-reducing conditions, a
      single band of apparent molecular mass 23.5-24.5 kDa was observed, whereas under
      reducing conditions the isoforms migrated as two distinct bands, 21.1-22.4 kDa
      and 18.0-20.5 kDa, probably corresponding to the alpha and beta subunits of hLH
      respectively. The remaining three less pure isoform preparations (70-90% pure)
      contained additional bands of 16 kDa and 26.3 kDa under non-reducing conditions.
      All isoforms showed a low molecular mass band(s) of 11-14 kDa which was < 7% of
      stained material as assessed by densitometry. Amino acid composition of the 17
      hLH isoforms was similar to the published cDNA composition of hLH. Further
      fractionation of one hLH isoform (hLH IIc) on reversed-phase high-performance
      liquid chromatography yielded four peaks identified by N-terminal sequencing as
      two alpha and two beta hLH subunits identical to their cDNA-derived N-terminal
      sequences. No additional sequences indicative of internal clipping of hLH were
      observed. The two pairs of alpha and beta subunits probably represent two
      separate hLH isoforms in this preparation. It was concluded that a mild
      purification procedure with high recoveries for the isolation of intact hLH
      isoforms has been developed, and 17 isoforms of high purity suitable for further
      biological and physicochemical characterization have been isolated. These isoform
      preparations are free of other contaminating proteins, but may still contain
      multiple hLH-related species.

PMID- 8277227
TI  - Concentration-dependent effects of adrenaline on the profile of insulin secretion
      from isolated human islets of Langerhans.
AB  - The effects of the mixed alpha/beta-agonist adrenaline on insulin secretion from
      isolated human islets of Langerhans were studied. In static incubation
      experiments, adrenaline (0.1 nmol/l to 10 mumol/l) caused a concentration
      dependent inhibition of glucose-induced insulin secretion from isolated human
      islets. However, perifusion experiments revealed that the time-course of the
      secretory changes induced by adrenaline was complex. When employed at a high
      concentration (1 mumol/l), adrenaline caused a sustained inhibition of glucose
      induced insulin secretion, which could be relieved by the addition of the alpha 2
      antagonist yohimbine (10 mumol/l). By contrast, infusion of adrenaline at a lower
      concentration (10 nmol/l), produced a large initial potentiation of glucose
      induced insulin secretion. This response was, however, short-lived and followed
      by sustained inhibition of secretion, which could be relieved by yohimbine (10
      mumol/l). The initial stimulation of insulin secretion provoked by 10 nmol
      adrenaline/l was abolished when islets were incubated in the presence of the beta
      antagonist, propranolol (1 mumol/l), consistent with activation of beta
      adrenoceptors. In support of this, treatment of human islets with the selective
      beta 2-agonist clenbuterol, was also associated with marked stimulation of
      insulin secretion. By contrast, each of two selective beta 3-agonists tested
      failed to alter insulin secretion from human islets. The results indicate that
      human pancreatic B-cells are equipped with both alpha 2- and beta 2-adrenoceptors
      which can affect insulin secretion. Adrenaline interacts with both of these but
      the alpha 2-response is predominant and can overcome the tendency of beta 2
      adrenoceptors to potentiate insulin release.

PMID- 8277228
TI  - Increased cytosolic free sodium concentrations in platelets from type 2 (non
      insulin-dependent) diabetic patients is associated with hypertension.
AB  - Cytosolic free sodium concentrations ([Na+]i) in intact platelets from 32 type 2
      (non-insulin-dependent) diabetic patients and from 27 age- and sex-matched non
      diabetic control subjects were measured with the novel sodium-sensitive
      fluorescent dye sodium-binding-benzofuran-isophthalate. [Na+]i was significantly
      higher in platelets from type 2 diabetic patients compared with control subjects
      (40.6 +/- 2.4 vs 32.0 +/- 2.0 mmol/l, means +/- S.E.M., P < 0.03). Both systolic
      and diastolic blood pressure were significantly elevated in diabetic patients
      compared with control subjects. Analysis of diabetic patients showed a
      significant association between [Na+]i and diastolic blood pressure (P = 0.026).
      Stimulation of Na/H exchange by thrombin increased [Na+]i in both groups. After
      inhibition of Na/K/ATPase by ouabain (1 mmol/l), [Na+]i was significantly
      increased both in diabetic patients and non-diabetic subjects in a similar way
      (by 40.2 +/- 7.3 and 31.7 +/- 5.3 mmol/l respectively). It is concluded that
      increased [Na+]i in cells from type 2 diabetic patients may be related to
      hypertension.

PMID- 8277229
TI  - 184th meeting of the Society for Endocrinology. London, 24-26 November 1993.
      Abstracts.

PMID- 8277230
TI  - Subcutaneous compliance and gravitational adaptation in snakes.
AB  - Previous studies have implicated morphological adaptations as important counter
      measures to gravitational stresses on the circulatory systems of arboreal or
      climbing snakes. Such features include tight skin and relatively non-compliant
      tissue compartments that oppose edema formation, but these traits have not been
      previously studied quantitatively. To provide information on this subject,
      interstitial fluid pressures were measured in eleven species of snakes using slit
      end catheters positioned in subcutaneous tissue located at the base of the tail.
      Interstitial pressures in all species were typically 0 to +2 mm Hg in normally
      hydrated tissue, but varied widely when snakes were active or when the tail was
      curved at the site of measurement. Local compliance of the free fluid space was
      determined from measurements of pressure while saline was infused via the
      catheter tip. Such measurements varied from 0.18 microliters/mm Hg in Philodryas
      baroni, an arboreal species, to 2.3 microliters/mm Hg in Crotalus adamanteus, a
      ground-dwelling, terrestrial species. In general, compliance of the subcutaneous
      tissue space was greatest (P < 0.05) in non-climbing and aquatic species of
      snakes that do not face problems of gravitational edema in dependent tissues.
      Presumably, the compliance measurements reflect adaptive structural differences
      related to requirements for counteracting gravitational stresses in the various
      species.

PMID- 8277231
TI  - Cloning of a crustacean myosin heavy chain isoform: exclusive expression in fast
      muscle.
AB  - A clone of a fast isoform of myosin heavy chain (HC) gene was isolated from a
      cDNA1 expression library made from mRNA purified from the deep abdominal flexor
      muscle of the lobster, Homarus americanus. The cDNA (1.5 kb) contained the 3'
      untranslated region (UTR) and the coding sequence for the last 413 amino acid
      residues of the carboxyl terminus of the polypeptide. The deduced amino acid
      sequence showed high homology with that of myosin HCs from Drosophila (73%
      identity), nematode (57% identity), and vertebrates (49% identities). Hydropathy
      plots showed a 28-amino acid periodicity that is consistent with the alpha
      helical coiled coil structure of the rod region of native myosin. Northern blot
      analysis and in situ hybridization showed that the fast myosin HC isoform was
      expressed only in fast fibers; the probes did not hybridize to mRNA from slow
      fibers. The message consisted of a single transcript of 6.6 kb. The intracellular
      localization of the fast myosin mRNA was not uniform. The mRNA was largely
      confined to the intermyofibrillar spaces and to the subsarcolemmal cytoplasm of
      the fiber periphery and large infoldings of the cell membrane. Within these
      regions the mRNA was concentrated in the cytoplasm immediately surrounding the
      nuclei. This constitutes the first report of the cloning and expression of a
      myosin HC gene from a crustacean species.

PMID- 8277232
TI  - In vitro spontaneous cytotoxic activity against mammalian target cells by the
      hemocytes of the solitary ascidian, Ciona intestinalis.
AB  - Blood cell-mediated cytotoxic activity against mammalian target cells by the
      hemocytes of the solitary ascidian Ciona intestinalis was investigated in vitro
      by fluorochromasia. Salt-conditioned target cells were labeled with
      carboxyfluorescein diacetate and challenged with mixed and separated hemocytes.
      The assay provided optimal conditions for the functioning of the effector
      hemocytes while maintaining low background leakage from the target cells.
      Comparison of different hemocyte populations, separated by density gradient
      centrifugation, revealed that only cell bands containing the phagocytic and
      nonphagocytic amoebocytes exhibited cytotoxicity. Experiments to characterize
      cytolysis demonstrated that activity increased with the effector to target cell
      ratio, occurred within 15 min, and was maximal at an incubation temperature of 20
      degrees C. Both human (K562) and mouse [YAC-1, P815, WEHI (3B) and L929] target
      cell lines were killed by the ascidian effector hemocytes. This paper
      demonstrates a population of nonspecific cytotoxic effector cells in the blood of
      C. intestinalis that are able to spontaneously kill a range of mammalian targets
      in vitro.

PMID- 8277233
TI  - Promises and perils of managed competition.

PMID- 8277234
TI  - Progress in childhood cancer care in Florida. 1970-1992.
AB  - Pediatric cancer has been a priority in Florida since 1970. That year physicians
      established a statewide network of children's tumor programs, the Florida
      Association of Pediatric Tumor Programs (FAPTP), which has grown from the initial
      two programs to 10 in 1992 and now maintains a registry with follow-up to monitor
      incidence and other indicators. State-of-the-art care is provided through
      affiliation with the Pediatric Oncology Group. The incidence of pediatric cancer
      in Florida is equivalent to national rates, but the number of children followed
      in 1991 had grown to approximately 2,000. The number receiving care has increased
      an average of 13% annually since 1981. Services for these patients should be
      reviewed on a continuing basis to assure access to specialized programs.

PMID- 8277235
TI  - Survey of Florida physicians. Characteristics and satisfaction.
AB  - Data from a 1991 physician survey jointly sponsored by the Florida Medical
      Association and the Florida Physicians Association are used to assess
      characteristics and satisfaction of Florida physicians in the current environment
      of increased managed care initiatives. Significant predictors of HMO affiliation
      include an urban practice location, a low proportion of Medicare patients, and
      Hispanic ethnicity. Income is negatively associated with HMO-affiliation,
      although not significantly. Physicians affiliated with HMOs are less satisfied
      than their counterparts with respect to current and future earnings, skills
      enhancement opportunities, time with patients, patient appreciation, specialty
      referral systems, overall quality of practice, opportunity to practice in desired
      manner, and overall satisfaction. Other results showed that Florida's primary
      care physicians are less satisfied than other physicians across some components
      of their practices. Also, HMO-affiliated physicians who participate in managerial
      decision-making are significantly more satisfied than other physicians.

PMID- 8277236
TI  - Chemical conjunctivitis caused by the spray of A. buprestoides. Two-striped
      walkingstick.
AB  - Most North American walkingsticks are harmless, but one species, A. buprestoides,
      can defend itself by spraying an irritating chemical. We present the first
      reported case in the medical literature of a chemical conjunctivitis caused by
      the spray of the two-striped walkingstick. The insect has the ability to direct a
      spray at a predator's eyes, inducing a self-limited conjunctivitis. Keratitis has
      been reported in a dog, and this may also be a possible complication in humans.
      Prudence is dictated in handling this insect, and physicians should be aware of
      the potential for injury to the eyes.

PMID- 8277237
TI  - Anchored proteins. Meeting of basic and clinical research.
AB  - A novel modification of proteins that make them lipophilic and capable of being
      tightly associated with membrane has been discovered in a variety of eukaryotic
      organisms, including man. Known as glycosyl phosphatidylinositol (GPI) anchor, it
      is profoundly deficient in the hemolytic disease, paroxysmal nocturnal
      hemoglobinuria (PNH). The molecular basis for this deficiency is due to the
      absence of the first enzyme in the biosynthetic pathway for the GPI anchor. Basic
      research on lower eukaryotes such as trypanosomes and yeasts formed the basis for
      the clinical discovery.

PMID- 8277238
TI  - Health insurance for preventive services.

PMID- 8277239
TI  - Starting to cycle: G1 controls regulating cell division in budding yeast.
AB  - In Saccharomyces cerevisiae, START has been shown to comprise a series of tightly
      regulated reactions by which the cellular environment is assessed and under
      appropriate conditions, cells are commited to a further round of mitotic
      division. The key effector of START is the product of the CDC28 gene and the
      mechanisms by which the protein kinase activity of this gene product is regulated
      at START are well characterized. This is in contrast to the events which follow
      p34CDC28 activation and the way in which progress to S phase is achieved, which
      are less clear. We suggest two possible models to describe the regulation of
      these events. Firstly, it is conceivable that the only post-START targets of the
      p34CDC28/G1 cyclin kinase complex are components of the SBF and DSC1
      transcription factors. This would require that either SBF or DSC1 regulates CDC4
      function either directly by activating the transcription of CDC4 itself or else
      indirectly by activating the transcription of a mediator of CDC4 function in a
      manner analogous to the way in which the control of CDC7 function may be mediated
      by transcriptional regulation of DBF4 (Jackson et al., 1993). Potential
      regulatory effectors of CDC4 function include SCM4, which suppresses cdc4
      mutations in an allele-specific manner (Smith et al., 1992) or its homologue HFS1
      (J. Hartley & J. Rosamond, unpublished). This possibility is supported by the
      finding that CDC4 has no upstream SCB or MCB elements, whereas SCM4 and HFS1 have
      either an exact or close match to the SCB. This model would further require that
      genes needed for bud emergence and spindle pole body duplication are also subject
      to transcriptional regulation by DSC1 or SBF. An alternative model is that the
      p34CDC28/G1 cyclin complexes have several targets post-START, one being DSC1 and
      the others being as yet unidentified components of the pathways leading to CDC4
      function, spindle pole body duplication and bud emergence. This model could
      account for the functional redundancy observed amongst the G1 cyclins with the
      various cyclins providing substrate specificity for the kinase complex. We
      suggest that a complex containing Cln3 protein is primarily responsible for, and
      acts most efficiently on, the targets containing Swi6 protein (SBF and DSC1),
      with complexes containing other G1 cyclins (Cln1 and/or Cln2 proteins)
      principally involved in activating the other pathways. However, there must be
      overlap in the function of these complexes with each cyclin able to substitute
      for some or all of the functions when necessary, albeit with differing
      efficiencies. This hypothesis is supported by several observations.(ABSTRACT
      TRUNCATED AT 400 WORDS)

PMID- 8277240
TI  - Stimulation of genetic instability in Streptomyces ambofaciens ATCC 23877 by
      antibiotics that interact with DNA gyrase.
AB  - In wild-type Streptomyces ambofaciens ATCC 23877, pigment-defective (Pig-)
      mutants arise at a frequency of about 0.5%; this genetic instability is related
      to genomic rearrangements such as deletions and/or amplifications of DNA
      sequences. On media containing oxolinic acid and novobiocin, which interact with
      the A and B subunits of DNA gyrase, respectively, the frequency of variants
      increased dramatically. The Pig- mutant frequency was increased to almost 100% on
      a medium containing oxolinic acid at a concentration allowing 55% survival. On
      solid medium containing either oxolinic acid or novobiocin at subinhibitory
      concentrations, most colonies exhibited a 'patchwork' phenotype, characterized by
      the presence of numerous Pig- sectors. Similar phenomena were not observed on
      media containing the transcriptional inhibitor rifampicin or the translational
      inhibitor streptomycin. Many of the Pig- mutants exhibited a pleiotropic
      phenotype and were affected in aerial mycelium formation, colony growth and/or
      prototrophy. Moreover, the same kinds of rearrangements (deletions and/or
      amplifications of DNA sequences) were found in both induced and spontaneous Pig-
      mutants. The results suggest either that DNA gyrase is directly involved in
      genetic instability or that an SOS-like system is implicated.

PMID- 8277241
TI  - Analysis of genome instability in Streptomyces ambofaciens.
AB  - Genetic instability in Streptomyces ambofaciens DSM 40697 is correlated with
      genomic instability characterized by multiple rearrangements (deletions and/or
      amplifications) occurring in a large unstable region. We have focused on one of
      the two amplifiable DNA loci which were mapped in this region: the amplifiable
      unit of DNA locus 6 (AUD6). The nucleotide sequence of one AUD6 fragment of 1.9
      kb reveals the presence of two open reading frames (ORF1 and ORF2) on the basis
      of the typical Streptomyces base composition at each of the three positions
      within codons. ORF1 shows some similarity with a gene encoding a regulatory
      protein. The presence of potential genes in this unstable locus was unexpected
      because deletions occurred with high frequency within this region in the genetic
      instability-derived mutant strains. However, transcription analyses by S1
      nuclease protection experiments on the wild-type strain showed transcription of
      both ORF1 and ORF2. Moreover, the amplified strain reveals increased
      transcription of ORF1 but no transcription of ORF2. The amplification therefore
      results in a switch in transcription. The unstable region of S. ambofaciens DSM
      40697 therefore is not a 'silent' region because at least some loci are
      transcribed.

PMID- 8277242
TI  - Functional and evolutionary implications of a survey of various actinomycetes for
      homologues of two Streptomyces coelicolor sporulation genes.
AB  - In Streptomyces coelicolor A3(2) the whiB and whiG genes are essential for
      sporulation, their deduced products being a possible transcriptional activator
      and an RNA polymerase sigma factor, respectively. In a survey of DNA from diverse
      actinomycetes by Southern blotting, all samples tested hybridized with whiB, but
      only those representing genera capable of producing sporulating aerial mycelium
      hybridized with whiG. It is postulated that whiB may play a more intimate role in
      hyphal fragmentation processes (including sporulation) than whiG. The whiB and
      whiG homologues (whiB-Stv and whiG-Stv) of Streptoverticillium griseocarneum were
      cloned and sequenced, and subjected to functional tests in S. coelicolor whiB and
      whiG mutants. The genes were closely similar, but not identical, to their S.
      coelicolor counterparts at the DNA and deduced protein levels, and both Stv.
      griseocarnum gene products could function well in S. coelicolor. However, studies
      with hybrid transcription units suggested that the promoter region of whiB-Stv is
      somewhat inefficient in S. coelicolor.

PMID- 8277243
TI  - The chromosomal location of genes for elongation factor Tu and ribosomal protein
      S10 in the cyanobacterium Spirulina platensis provides clues to the ancestral
      organization of the str and S10 operons in prokaryotes.
AB  - The structural gene (rps10) encoding ribosomal protein S10 of the cyanobacterium
      Spirulina platensis has been localized both on chromosomal DNA and the previously
      characterized recombinant plasmid pSp7 harbouring the 3'-terminal portion of the
      gene for elongation factor G (fus) and the gene for elongation factor Tu (tuf).
      Alignment of the predicted S10 sequence of S. platensis with the homologous
      sequences from cyanelles, bacteria, archaea and eukarya showed that the
      cyanobacterial S10 shares a high degree of sequence homology (74% amino acid
      identity) with the cyanellar protein. Unlike the situation in Escherichia coli,
      the rps10 gene of S. plantensis is unlinked to the S10 operon genes, being
      adjacent to the str operon genes. Since a similar organization could be observed
      in cyanelles of Cyanophora paradoxa and in all archaea so far analysed, this
      probably represents the ancestral state.

PMID- 8277244
TI  - Genetic structure of Neisseria gonorrhoeae populations: a non-clonal pathogen.
AB  - Reproduction by binary fission generates a clonal genetic structure in bacterial
      populations in the absence of a high rate of recombination. The extent of
      recombination in natural populations of Neisseria gonorrhoeae was determined from
      an analysis of electrophoretically demonstrable allelic variation at structural
      genes encoding nine enzyme loci in 227 worldwide isolates. No significant linkage
      disequilibrium was evident in the population, indicating that recombination must
      be frequent, relative to binary fission. The genetic structure of N. gonorrhoeae
      was compared with that of Bacillus subtilis from an earlier study. Linkage
      disequilibrium was less extreme in the N. gonorrhoeae population than in the
      local population of B. subtilis, in which only modest clonal structure was
      evident. Thus, N. gonorrhoeae, unlike pathogens so far examined, has a non-clonal
      population structure. As expected in a freely recombining population, no
      correlation was found between electrophoretic genotype and serovar or auxotype.

PMID- 8277245
TI  - Evidence for Chlamydia pneumoniae of non-human origin.
AB  - This paper describes the characterization and taxonomic status of N16, a
      chlamydial isolate from the respiratory tract of a horse. N16 contains plasmid
      DNA, has normal elementary body morphology and its inclusions do not stain with
      iodine. Its major outer-membrane protein (MOMP) gene was completely sequenced and
      compared with the MOMP genes of Chlamydia pneumoniae, C. psittaci, C. trachomatis
      and C. pecorum. This analysis revealed that N16 is closely related to the TWAR
      strain of C. pneumoniae (94.5% and 94.4% DNA homology with TWAR isolates IOL-207
      and AR-39 respectively). By comparison, N16 shows between 72.1% and 73.7% DNA
      homology with C. psittaci strains, 70.9% and 71.1% homology with C. pecorum
      strains LW613 and 1710S and 69.2% homology with C. trachomatis serotype E. The
      MOMP gene of N16 shares 93.8% DNA homology with the MOMP gene of a chlamydial
      isolate KC from the conjunctiva of a koala. Monoclonal antibodies raised to C.
      pneumoniae IOL-207 and shown to be C. pneumoniae-specific confirmed that N16 was
      more closely related to C. pneumoniae than to C. psittaci. Thus DNA homology and
      monoclonal antibody data both suggest that horse chlamydiae, as exemplified by
      N16, form a new second strain of C. pneumoniae. This species is probably more
      widespread and diverse than the current literature would suggest.

PMID- 8277246
TI  - Isolation, classification and molecular characterization of bacteriophages for
      Enterobacter species.
AB  - Out of 22 Enterobacter phages investigated, nine were found to be suitable for
      phage typing based on their different lytic spectra on 398 strains of
      Enterobacter spp. isolated from milk powder and other foods. These phages were
      compared on the basis of morphology, protein composition, restriction
      endonuclease patterns and DNA-DNA hybridization. Two phages (WS-EP19, WS-EP13)
      belonged to the Podoviridae family (morphotype C1), and three (WS-EP20, WS-EP26,
      WS-EP28) were classified as Siphoviridae (morphotype B1). The other four phages
      were Myoviridae of the morphological groups A1 (WS-EP57) and A2 (WS-EP32, WS
      EP94, WS-EP96). SDS-PAGE revealed individual protein profiles for each phage,
      which corresponded to different restriction enzyme fragment patterns. DNA-DNA
      hybridization demonstrated the close relationship of phages WS-EP20 and WS-EP26,
      and of WS-EP94 and WS-EP96. In general, a good correlation was found between
      groupings obtained with the various methods. The nine phages could be attributed
      to existing enterobacterial phage species although some differences to the
      described type phages were observed.

PMID- 8277247
TI  - Immunological specificity of oral Eubacterium species.
AB  - Antigens of Eubacterium species including E. alactolyticum, E. brachy, E.
      nodatum, E. saburreum, E. timidum, E. yurii subsp. yurii and E. yurii subsp.
      margaretiae, which have been isolated frequently from periodontal pockets and
      associated with periodontal diseases, were extracted by ultrasonication from
      whole bacterial cells. Antigens were also prepared from E. aerofaciens, E. lentum
      and E. rectale, which have been found in intestinal tracts and infected abscesses
      in human oral cavities. The antigens of the oral Eubacterium species were
      compared with antigens from E. limosum, the type species of the genus
      Eubacterium, by using SDS-PAGE and Western immunoblot assays. SDS-PAGE gels
      stained with Coomassie brilliant blue indicated that no major peptide bands were
      common among the Eubacterium species examined. The protein profile patterns were
      distinctly different from each other. Western immunoblotting reactions with
      rabbit antisera showed that the Eubacterium species could be clearly
      distinguished serologically, and that the species-specific antigens were peptide
      components of ultrasonic extracts from the whole bacterial cells. The present
      study demonstrates that these Eubacterium species show great heterogeneity in
      their peptide components and immunological reactions, which may be useful for
      identification of the Eubacterium species from human oral specimens.

PMID- 8277248
TI  - Structure and antigenicity of lipoarabinomannan from Mycobacterium bovis BCG.
AB  - Lipoarabinomannan (LAM), a major lipoglycan of the mycobacterial cell envelope,
      was previously recognized as existing in two major forms: LAM with
      arabinofuranosyl (Araf)-containing termini (AraLAM) and a mannose-capped version
      (ManLAM) in which the majority of these termini are modified by additional
      mannose residues. Since ManLAM was first recognized in the virulent (Erdman)
      strain of Mycobacterium tuberculosis and the noncapped version in a rapidly
      growing, attenuated, H37Ra strain, it was thought that mannose capping may be a
      key factor in virulence. In the present study, LAM from M. bovis BCG was isolated
      and the non-reducing termini sequenced through differential O-alkylation, partial
      depolymerization and gas chromatography-mass spectrometric analyses of fragments.
      LAM from M. bovis BCG contains a short mannan backbone, highly branched
      arabinofuranosyl-containing side chains and several mannosyl residues capping the
      non-reducing termini of these side chains. Thus, LAM from M. bovis BCG is of the
      ManLAM type, showing no major structural differences at the non-reducing ends
      from the M. tuberculosis Erdman product. This observation led us to examine the
      earlier strain and to conclude that it showed little resemblance to conventional
      strains of M. tuberculosis. Thus, the absence of mannose caps may be more a
      feature of rapid growth than of avirulence. These results demonstrate that the
      relationship between mannose capping and disease induction is not a simple one.
      However, use of a panel of LAM-specific monoclonal antibodies showed antigenic
      differences between the BCG and the Erdman products, suggesting the presence of
      features specific to the different strains and pointing to LAM as a molecule
      within which further species and strain variations reside.

PMID- 8277249
TI  - Biological activities of lipoteichoic acid and peptidoglycan-teichoic acid of
      Bacillus subtilis 168 (Marburg).
AB  - To evaluate the suitability of Bacillus subtilis as a production host of
      heterologous proteins for pharmaceutical purposes, we assessed the biological
      activity of this bacterium and its major cell envelope components, lipoteichoic
      acid (LTA) and peptidoglycan-teichoic acid complex (PG-TA) in several eukaryotic
      effector assays. LTA and PG-TA were found to be non-toxic for mice and guinea
      pigs in a short-term toxicity assay. PG-TA was weakly pyrogenic and weakly
      mitogenic. Both LTA and PG-TA acted as immunologic adjuvants in mice and when
      injected in mice, also caused an increase in the number of granulocyte-monocyte
      colony-forming cells in the bone marrow probably via stimulation of production of
      granulocyte-macrophage colony-stimulating factor.

PMID- 8277250
TI  - The draTG gene region of Rhodobacter capsulatus is required for post
      translational regulation of both the molybdenum and the alternative nitrogenase.
AB  - Synthetic oligonucleotides, which were designed according to amino acid sequences
      conserved between Rhodospirillum rubrum and Azospirillum brasilense DraT and
      DraG, respectively, were used to identify the corresponding genes of Rhodobacter
      capsulatus. Sequence analysis of a 1904 bp DNA fragment proved the existence of
      R. capsulatus draT and draG. These two genes were separated by 11 bp only,
      suggesting that R. capsulatus draT and draG were part of one transcriptional
      unit. In contrast to R. rubrum, A. brasilense and Azospirillum lipoferum, the R.
      capsulatus draTG genes were not located upstream of the structural genes of
      nitrogenase nifHDK but close to the dctP gene at a distance of about 1000 kb from
      the nifHDK genes. Deletion mutations in the draTG gene region were constructed
      and introduced into R. capsulatus wild-type and a nifHDK deletion strain. The
      resulting mutant strains were examined for post-translational regulation of the
      molybdenum and the alternative nitrogenase in response to ammonia and darkness.
      Under 'switch-off' conditions the modified (ADP-ribosylated) and the non-modified
      forms of component II of both the molybdenum and the alternative nitrogenase were
      detected in a draTG wild-type background by immunoblot analysis, whereas only the
      non-modified forms were present in the draTG deletion strains. Nitrogenase
      activity in these strains was followed by the acetylene reduction assay. In
      contrast to the wild-type, draTG mutants were not affected in nitrogenase
      activity in response to ammonia or darkness. These results demonstrated that the
      draTG genes are required for post-translational regulation of both the molybdenum
      and the heterometal-free nitrogenase in R. capsulatus.

PMID- 8277251
TI  - Characterization of regulatory mutations causing anaerobic derepression of the
      sodA gene in Escherichia coli K12: cooperation between cis- and trans-acting
      regulatory loci.
AB  - The genetic loci leading to anaerobic derepression of a sodA::lacZ protein fusion
      in a UV-generated mutant strain (UV14) of Escherichia coli were identified. The
      mutant (UV14) was found to harbour two altered loci: one is in the trans
      regulatory gene fnr (fumarate nitrate reduction) where leucine-129 was changed to
      glutamine (fnr14), and the second (sodA14) is in the promoter region (cis) of the
      sodA gene apparently affecting the binding of the Fur (ferric uptake regulation)
      protein. Introduction of an fnr+ gene into UV14 restored anaerobic repression of
      sodA::lacZ and restored the ability of the cells to reduce nitrate. However, when
      either the fnr14 or the sodA14 mutation was introduced into an otherwise wild
      type background, only slight anaerobic derepression of sodA was observed. When
      both the cis- and trans-acting mutations (i.e. sodA14 and fnr14) were combined
      simultaneously in an otherwise wild-type background, the specific activity of
      sodA::lacZ expression was comparable to that of the original mutant strain
      (UV14). Furthermore, a genetically confirmed fur fnr double mutant was also
      similarly derepressed in anaerobic sodA::lacZ expression. The data presented
      suggest that the cis-mutation in UV14 (sodA14) affects the Fur-binding site in
      the sodA promoter, while having no effect on Fnr or Arc mediated repression.
      Also, a second putative Fnr-binding site that straddles the ribosomal binding
      site was identified in the sodA gene.

PMID- 8277252
TI  - Isolation, characterization and nucleotide sequence of the Streptococcus mutans
      lactose-specific enzyme II (lacE) gene of the PTS and the phospho-beta
      galactosidase (lacG) gene.
AB  - The lacE and lacG genes from Streptococcus mutans have been isolated and
      characterized, and their nucleotide sequence has been determined. The lacE gene
      encodes the lactose-specific Enzyme II component of the phosphoenolpyruvate
      dependent phosphotransferase system (PTS). The lacG gene encodes the phospho-beta
      galactosidase which cleaves the lactose phosphate that is formed by the lactose
      PTS. The S. mutans lacE and lacG genes are located in the same operon as the
      tagatose genes. S. mutans metabolizes lactose via the tagatose phosphate pathway.
      The deduced LacE and LacG proteins of S. mutans display high homology with the
      corresponding proteins from Lactococcus lactis, Staphylococcus aureus and
      Lactobacillus casei.

PMID- 8277253
TI  - Conservation of regulatory and structural genes for a multi-component phenol
      hydroxylase within phenol-catabolizing bacteria that utilize a meta-cleavage
      pathway.
AB  - Pseudomonas sp. strain CF600 can degrade phenol and some of its methylated
      derivatives via a plasmid (pVI150)-encoded pathway. The metabolic route involves
      hydroxylation by a multi-component phenol hydroxylase and a subsequent meta
      cleavage pathway. All 15 structural genes involved are clustered in an operon
      that is regulated by a divergently transcribed transcriptional activator. The
      multi-component nature of the phenol hydroxylase is unusual since reactions of
      this type are usually accomplished by single component flavoproteins. We have
      isolated and analysed a number of marine bacterial isolates capable of degrading
      phenol and a range of other aromatic compounds as sole carbon and energy sources.
      Southern hybridization and enzyme assays were used to compare the catabolic
      pathways of these strains and of the archetypal phenol-degrader Pseudomonas U,
      with respect to known catabolic genes encoded by Pseudomonas CF600. All the
      strains tested that degraded phenol via a meta-cleavage pathway were found to
      have DNA highly homologous to each of the components of the multicomponent phenol
      hydroxylase. Moreover, DNA of the same strains also strongly hybridized to probes
      specific for pVI150-encoded meta-pathway genes and the specific regulator of its
      catabolic operon. These results demonstrate conservation of structural and
      regulatory genes involved in aromatic catabolism within strains isolated from
      diverse geographical locations (UK, Norway and USA) and a range of habitats that
      include activated sludge, sea water and fresh-water mud.

PMID- 8277254
TI  - Dimensional rearrangement of Escherichia coli B/r cells during a nutritional
      shift-down.
AB  - In a search for the mechanism underlying dimensional changes in bacteria, the
      glucose analogue methyl alpha-D-glucoside was used to effect a rapid reduction in
      the mass growth rate of Escherichia coli by competitively inhibiting glucose
      uptake, a so-called nutritional shift-down. The new steady-state cell mass and
      volume were reached after 1 h, during which the rate of cell division was
      maintained; rearrangement of the linear dimensions (cell length, diameter),
      however, required an additional 2 h and caused an undershoot in cell length,
      consistent with the view that E. coli is slow to modify its diameter. The results
      are compared with the overshoot in cell length that occurs following nutritional
      shift-up.

PMID- 8277255
TI  - Dependence of induction of enterobacterial AmpC beta-lactamase on cell-wall
      peptidoglycan, as demonstrated in Proteus mirabilis and its wall-less protoplast
      L-form.
AB  - The mobilizable plasmid pMD101 (ampR, ampC) was constructed by inserting cloned
      ampC, the structural gene for the chromosomal AmpC beta-lactamase of Citrobacter
      freundii, and the closely linked ampR encoding the transcriptional regulator
      essential for enzyme induction, into the broad host-range plasmid pKT231. Plasmid
      pMD101 was transconjugated into Proteus mirabilis VI and its isogenic, cell-wall
      less protoplast L-form LVI. AmpC beta-lactamase was expressed constitutively from
      cloned ampR and ampC in bacteria and in some L-form protoplasts. However,
      induction of the enzyme by beta-lactam antibiotics occurred only in bacterial
      cells and not in the cell-wall- and peptidoglycan-deficient L-form. In agreement
      with current models, induction of AmpC beta-lactamase is thought to be initiated
      by an induction signal arising from the metabolic disturbance of cell-wall
      peptidoglycan.

PMID- 8277256
TI  - In vitro biosynthesis of acetan using electroporated Acetobacter xylinum cells as
      enzyme preparations.
AB  - Acetobacter xylinum strain NRRL B42 and its derivative RCGr1 produce a complex
      exopolysaccharide, acetan, containing glucose, mannose, glucuronic acid and
      rhamnose in a 4:1:1:1 molar ratio. The in vitro synthesis of acetan, employing
      electroporated cells as the enzyme system and the respective 14C-labelled sugar
      nucleotide precursors, is described. The synthesis of the prenyl-linked
      heptasaccharide repeat unit, already observed in EDTA-treated cells, was
      confirmed, as well as the formation of other saccharides not related to acetan
      biosynthesis, including a high molecular mass glucan. The acetan formed was
      characterized by gel filtration, specific radioactive labelling with each
      precursor and permethylation analysis. It was also shown that acetan contains
      acetyl residues and that using [14C]acetyl CoA as donor, radioactivity was
      detected both at the polysaccharide and at the prenyl-linked oligosaccharide
      stage.

PMID- 8277257
TI  - Catabolism of isonicotinate by Mycobacterium sp. INA1: extended description of
      the pathway and purification of the molybdoenzyme isonicotinate dehydrogenase.
AB  - Catabolism of isonicotinate by Mycobacterium sp. INA1 has been shown to proceed
      via 2-hydroxyisonicotinate, 2,6-dihydroxyisonicotinate (citrazinate), citrazyl
      CoA and 2,6-dioxopiperidine-4-carboxyl-CoA. An extended pathway involving propane
      1,2,3-tricarboxylate as a further intermediate is presented in this paper.
      Propane-1,2,3-tricarboxylate was oxidized stepwise to 2-oxoglutarate involving an
      oxidase, aconitase and isocitrate dehydrogenase. Isonicotinate dehydrogenase
      catalyses the first step of isonicotinate metabolism in Mycobacterium sp. INA1.
      The enzyme was purified to apparent homogeneity by a three-step procedure.
      Enrichment was accompanied by partial loss in specific activity. The native
      enzyme had a molecular mass of either 125 kDa or 250 kDa, when estimated by
      native gradient PAGE or gel filtration, respectively. SDS-gel electrophoresis
      revealed three types of subunits with molecular masses of approximately 83, 31
      and 19 kDa. N-Terminal amino acid sequences of all three subunits have been
      determined. Molybdenum, iron, acid-labile sulphur and FAD were present at molar
      ratios of 1, 4, 4, 1 per protomer (125 kDa). The molybdenum-complexing cofactor
      was shown to be molybdopterin cytosine dinucleotide. Besides isonicotinate, only
      quinoline-4-carboxylate was found to be oxidized at appreciable rates.

PMID- 8277258
TI  - Activities of the enzymes of the Ehrlich pathway and formation of branched-chain
      alcohols in Saccharomyces cerevisiae and Candida utilis grown in continuous
      culture on valine or ammonium as sole nitrogen source.
AB  - Valine aminotransferase, a key enzyme in both biosynthesis and breakdown of
      branched-chain amino acids, showed consistently higher activity in Candida utilis
      grown in continuous culture than in Saccharomyces cerevisiae, while pyruvate
      decarboxylase and alcohol dehydrogenase, the other two enzymes of the Ehrlich
      pathway of branched-chain alcohol formation, were lower in activity. By
      spheroplast lysis, it was shown that valine aminotransferase followed the
      distribution of pyruvate decarboxylase in being located in the cytosol.
      Replacement of ammonium as nitrogen source by valine during conditions of carbon
      or nitrogen limitation caused increased specific activities of these three
      enzymes in S. cerevisiae, but (with one exception) decreased those of C. utilis.
      Of the metabolites accumulating in the culture medium, little or no ethanol or
      branched-chain alcohols were present during carbon-limited growth of either
      organism, but the change to nitrogen limitation resulted in increases in
      concentration of 20- to 100-fold in pyruvate, acetate and non-pyruvate keto acids
      as well as the accumulation of branched-chain alcohols in both organisms, and of
      ethanol, ethyl acetate and glycerol in S. cerevisiae. When valine was the
      limiting nitrogen source, there was an increase in non-pyruvate keto acids and a
      10- to 16-fold increase in 2-methylpropanol. Total branched-chain alcohols formed
      under nitrogen limitation were 2-fold higher in S. cerevisiae than in C. utilis,
      irrespective of nitrogen source. Accumulation of branched-chain alcohols,
      ethanol, acetate and glycerol was also observed during carbon-limited growth of
      S. cerevisiae with valine as nitrogen source at dilution rates above the critical
      rate for transition to respirofermentative growth. Less than 70% of the valine
      carbon metabolized during growth of S. cerevisiae and only 15% of that used
      during growth of C. utilis was recovered in identified metabolic products. Even
      allowing for losses by volatilization during aeration, this suggests that a
      significant amount of the valine is being metabolized by a route or routes other
      than the Ehrlich pathway, possibly via the action of branched-chain 2-keto acid
      dehydrogenase. The molar growth yield for the nitrogen source under either carbon
      or nitrogen limitation was significantly lower for growth on valine than for
      growth on ammonium, suggesting that breakdown of valine requires more energy. It
      is evident that not all the enzymes involved in branched-chain amino acid
      metabolism in yeasts have yet been identified, nor are their interactions
      properly understood.

PMID- 8277259
TI  - Purification and characterization of glucose-6-phosphate dehydrogenase from
      Aspergillus niger and Aspergillus nidulans.
AB  - Glucose-6-phosphate dehydrogenase (G6PD; D-glucose 6-phosphate:NADP+
      oxidoreductase, EC 1.1.1.49) has been purified from Aspergillus nidulans and
      Aspergillus niger by a combination of affinity and anion exchange chromatography.
      A 500-1000-fold purification was obtained and the final enzyme preparations were
      shown to be pure but not homogeneous. For both fungi the purified enzyme
      preparation gave two bands on native and denaturing gels. The catalytically
      active form is a multimer. The molecular mass of the monomers is 60 and 57 kDa
      for A. nidulans and 55 and 53 kDa for A. niger. Both enzymes exhibited strict
      specificity towards both substrates glucose 6-phosphate and NADP+. The A.
      nidulans and A. niger G6PD enzymes catalyse the conversion of glucose 6-phosphate
      via a random order mechanism. Inhibition studies provided evidence for the
      physiological role of G6PD as producer of NADPH in both fungi.

PMID- 8277260
TI  - Growth and product formation in chemostat and recycling cultures by Aspergillus
      niger N402 and a glucoamylase overproducing transformant, provided with multiple
      copies of the glaA gene.
AB  - Continuous and recycling cultures were carried out with Aspergillus niger N402
      wild-type and a glucoamylase overproducing transformant to investigate growth and
      product formation characteristics. In shake flask cultures, the amount of
      glucoamylase produced by the transformant was about five times more than by the
      wild-type strain. In contrast with these results, a twofold overproduction was
      found in glucose-limited continuous cultures, while no overproduction was found
      under maltodextrin-limitation. Two regions of specific growth rates could be
      distinguished, one at specific growth rates lower (domain I) and one at specific
      growth rates higher than 0.12 h-1 (domain II). In domain I changes in mycelium
      morphology and conidia formation were observed. It has been concluded that
      maintenance requirements are dependent on the specific growth rate over the whole
      range of measured growth rates. The deviation in linearity in the linear equation
      of substrate utilization, caused by this phenomenon, should be considered when
      continuous cultures with filamentous fungi are performed. In recycling cultures,
      xylose as limiting carbon source repressed glucoamylase production very strongly.
      Under maltodextrin-limitation a fivefold overproduction was found. After about
      150 h , the total amount of glucoamylase produced was still increasing, while
      total amount of product, measured as carbon, remained constant. After this time
      no increase in the amount of biomass formed was observed. These results suggest
      autolysis and cryptic growth taking place in a recycling fermenter and cell death
      rate equalling growth rate.

PMID- 8277261
TI  - Periodic selection in longterm continuous-flow cultures of the filamentous fungus
      Fusarium graminearum.
AB  - By monitoring increases and decreases in the proportion of cycloheximide
      resistant macroconidia, periodic selection was observed in populations of the
      filamentous fungus Fusarium graminearum, grown in glucose-limited chemostat
      cultures. The results indicated that periodic selection of advantageous mutants
      of F. graminearum occurred at intervals of about 124 h at both high (D = 0.19 h
      1, approximately 34 generations) and low (D = 0.06 h-1, approximately 11
      generations) dilution rates. Several 'adaptive' peaks (each indicating the
      appearance of an advantageous mutation) were observed before morphological
      (highly branched) mutants appeared in the populations; these mutants have
      previously been observed to have a selective advantage over the parental strain.
      At intervals, macroconidia harvested from the chemostat were used to inoculate
      plates of non-antibiotic-containing agar medium, and it was possible to monitor
      periodic selection in the original chemostat culture using second generation
      macroconidia harvested from these cultures. The proportion of cycloheximide-,
      potassium chlorate-, and p-fluoro-DL-phenylalanine-resistant macroconidia in
      these second generation macroconidia changed in a pattern similar to that
      observed when monitoring the proportion of cycloheximide-resistant macroconidia
      in the first generation population harvested directly from the chemostat. The
      experiments demonstrated that populations of filamentous fungi are heterogeneous
      and that much of this heterogeneity may already be present at the end of batch
      growth, i.e., before the onset of continuous cultivation.

PMID- 8277262
TI  - Analysis of bacterial phospholipid markers and plant monosaccharides during
      forage degradation by Ruminococcus flavefaciens and Fibrobacter succinogenes in
      co-culture.
AB  - Marker components of the phospholipids of Ruminococcus flavefaciens and
      Fibrobacter succinogenes were identified for studies on the degradation of forage
      by these bacteria growing in mixed culture. The principal fatty acid methyl
      esters and dimethyl acetals detected varied between strains and were influenced
      by the addition of a mixture of higher volatile fatty acids and vitamins to the
      medium, but these effects were small compared to the differences between the
      species. When two strains of R. flavefaciens were grown on a mixture of clover
      and ryegrass, and on barley straw in the presence or absence of two strains of F.
      succinogenes, the solubilization of plant material tended to be lowered by the
      presence of F. succinogenes. R. flavefaciens was the predominant bacterium among
      colonies recovered from roll tubes, and the phospholipids were primarily those of
      R. flavefaciens. Analysis of the culture supernatant liquids showed that F.
      succinogenes produced greater amounts of free and bound xylose from both clover
      and straw than did R. flavefaciens. With both forages, cultures containing the
      two species produced more soluble free arabinose, and less soluble-bound
      arabinose, than either species grown alone.

PMID- 8277263
TI  - RNA editing in Newcastle disease virus.
AB  - The co-transcriptional editing of the Newcastle disease virus (NDV) P gene has
      been studied by sequence analysis of cloned viral genomic RNA and mRNA. Evidence
      has been obtained for the specific insertion of non-templated G nucleotides, the
      consequence of which is the generation of three populations of P gene-derived
      mRNAs. The three populations encode proteins (P, V and W) which have a common N
      terminal region, but which utilize three different reading frames at their C
      termini. Paradoxically, NDV edits its P gene mRNA by the insertion of non
      templated G residues in a manner similar to Sendai and measles viruses (P-->V
      editing) despite its apparent closer evolutionary relationship to the simian
      virus type 5, mumps and related group of viruses which edit a V genomic sequence
      to generate an mRNA to encode a functional P protein (V-->P editing).

PMID- 8277264
TI  - An immunodominant cytotoxic T cell epitope on the VP7 rotavirus protein overlaps
      the H2 signal peptide.
AB  - C57BL/6 (H-2b) mice were primed with the bovine RF strain of rotavirus to study
      the induction of CD8+ cytotoxic T lymphocytes (CTLs). These rotavirus-specific
      CTLs were detected only after in vitro restimulation with the virus. Using a
      recombinant vaccinia virus we identified the RF VP7 protein as a major target of
      these CTLs. The response against this protein was obtained also after in vitro
      restimulation with simian SA11 and human WA strains of rotavirus. Using published
      Db and Kb allele-specific motifs to predict possible CTL epitopes in the RF VP7
      protein, we synthesized and tested 18 predicted peptides of VP7. Only one peptide
      was able to sensitize target cells at a concentration below 5 x 10(-7) M. This
      CTL epitope was also induced by immunization with the RF VP7 expressed with a
      baculovirus vector, and was shown to be immunodominant by its capacity to
      inhibit, in an unlabelled target assay, the bulk response against cells infected
      with recombinant vaccinia virus expressing VP7. This CTL epitope overlaps the H2
      signal peptide of the protein.

PMID- 8277265
TI  - Influence of the human immunodeficiency virus type 1 Tat protein on the
      proliferation and differentiation of PC12 rat pheochromocytoma cells.
AB  - Rat pheochromocytoma PC12 cells were permanently transfected with a plasmid
      vector, containing the tat gene of human immunodeficiency virus type 1 (HIV-1).
      Various clones were obtained showing the production of different levels of
      bioactive Tat protein (Tat) after transient cotransfection with an HIV-1 long
      terminal repeat-chloramphenicol acetyltransferase reporter plasmid. Under
      conditions of serum starvation, tat-positive PC12 clones expressing high levels
      of Tat showed a significantly (P < 0.05) higher proliferation rate with respect
      to both mock-transfected PC12 cells and tat-positive PC12 cells expressing lower
      levels of Tat. Moreover, all tat-positive PC12 cell clones showed a partial
      morphological differentiation into sympathetic-like neurons, when seeded in low
      density (5 x 10(3) cells/cm2) cultures. On the other hand, mock-transfected PC12
      cells showed the round shaped morphology typical of untreated PC12 cells and
      displayed signs of neuronal differentiation only after treatment with 100 ng/ml
      of nerve growth factor. The addition of 5 micrograms/ml of anti-Tat monoclonal
      antibody to the culture medium of tat-positive PC12 cell clones almost completely
      blocked their increased proliferation rate (P < 0.05), but did not affect
      neuronal differentiation. A significant (P < 0.05) increase in cell proliferation
      was consistently observed in PC12 cells supplemented with low concentrations of
      Tat (5 to 25 ng/ml), whereas neuronal differentiation was hardly affected by
      exogenous Tat. Our data strongly suggest that Tat exerts a complex influence on
      the proliferation and differentiation of PC12 cells, and this might help in
      increasing understanding of the pathogenesis of the frequent neurological
      disorders observed in AIDS patients.

PMID- 8277266
TI  - Virus-free survival and down-regulation of CD4 in C8166 cells infected with human
      immunodeficiency virus type 1 at low density.
AB  - Compared with other T cell lines, C8166 lymphocytes are particularly susceptible
      to human immunodeficiency virus (HIV) infection and the outcome is invariably
      cell death. The results reported in this study demonstrate that the virus-induced
      cytolysis is strongly dependent on the initial cell density of C8166 cultures.
      Cultures diluted to 50 to 500 cells/ml almost completely maintained their cell
      duplication rate and released infectious virus into the medium. HIV infection of
      diluted C8166 cells is a simple and easily reproducible procedure for obtaining
      persistently infected cultures. These cultures contained genomic and extragenomic
      HIV DNA, the latter being assayed by PCR for two-long terminal repeat circular
      forms. The status of persistent infection disappeared within 2 months. The
      recovery is due to the replacement of CD4 down-regulated infected cells by
      overgrowing uninfected cell variants, which are transcriptionally inactive for
      CD4. The mechanisms underlying the emergence of these variants in persistently
      infected cultures are considered.

PMID- 8277267
TI  - The cytopathic effect of human immunodeficiency virus is independent of high
      levels of unintegrated viral DNA accumulated in response to superinfection of
      cells.
AB  - Large quantities of genome-sized viral DNA are detected in the nucleoplasm of
      CD4+ T cells infected with human immunodeficiency virus type 1 (HIV-1). This
      unintegrated HIV DNA is in the form of both circular and linear species.
      Accumulation of such DNA occurs gradually during a 5 day HIV infection and is
      correlated with the proportion of cells involved in the production of HIV
      proteins. To pinpoint the stage in a synchronized HIV infection during which
      accumulation of HIV DNA occurs, high titres of HIV were employed to infect CEM
      cells to infect the majority of cells by the input virus. By this latter
      infection, more than 95% of cells became producers of HIV proteins at 48 h post
      infection (p.i.) concomitantly with the development of the c.p.e. of HIV,
      manifested by formation of syncytia and induction of cell death by apoptosis.
      Addition of azidothymidine (AZT) or neutralizing anti-gp120 monoclonal antibodies
      at 8 h p.i. did not alter the course of virus infection nor the amount of virus
      produced at 48 h p.i. but the accumulation of unintegrated HIV DNA was
      drastically reduced. These results indicate that viral DNA accumulates as a
      result of superinfection of cells late in the virus cycle. The development of the
      c.p.e. of HIV was inhibited in the presence of neutralizing antibodies, whereas
      in the presence of AZT the accumulation of unintegrated HIV DNA was completely
      blocked without apparent effect on the c.p.e. These observations indicate that
      the c.p.e. of the HIV infection, which is manifested by syncytium formation and
      apoptosis, does not require superinfection of cells or accumulation of
      unintegrated viral DNA.

PMID- 8277268
TI  - Avian sarcoma virus RNA synthesis, RNA splicing and virus production in human
      foreskin fibroblasts: effect of co-infection with human cytomegalovirus.
AB  - The level of RNA transcripts in human foreskin fibroblast (HFF) cells initiated
      from the avian sarcoma virus (ASV) long terminal repeat (LTR) promoter was
      stimulated more than 10-fold when the cells were also infected with human
      cytomegalovirus (HCMV). HCMV was able to stimulate transcription from the ASV LTR
      promoter even when all the LTR sequence upstream of the TATA box was deleted,
      suggesting that only the basal LTR promoter is required for the effect. There
      were no significant changes in the ASV RNA splicing pattern in stimulated and
      unstimulated HFF cells. The mRNAs showing an increase during HCMV stimulation
      included aberrantly spliced ASV RNA species as well as unspliced gag-pol, single
      spliced env and single-spliced src mRNAs. This pattern was quite different from
      ASV splicing in chicken embryo fibroblasts (CEF) but typical of that seen in
      other mammalian cells. A dramatic increase in infectious ASV production from the
      normally non-permissive HFF was correlated with the increase in amount of ASV RNA
      in response to HCMV. Thus, there is not an absolute block to ASV production in
      human cells. However, infectious ASV production was inefficient in HCMV
      stimulated HFF compared to that in CEF cells.

PMID- 8277269
TI  - Partial cloning of the genome of infectious hypodermal and haematopoietic
      necrosis virus, an unusual parvovirus pathogenic for penaeid shrimps; diagnosis
      of the disease using a specific probe.
AB  - The infectious hypodermal and haematopoietic necrosis virus (IHHNV), pathogenic
      for penaeid shrimp, is an icosahedral unenveloped particle, 22 nm in diameter,
      with an ssDNA linear genome, and proposed to be a member of the Parvoviridae. A
      large majority of minus-strand DNA is incorporated into the capsids compared to
      the plus-strand. A small amount of reannealed plus- and minus-strands (dsDNA)
      obtained after nucleic acid extraction was blunt-ended and cloned into the system
      pUC18/Escherichia coli strain DH5 alpha. Selected clones were studied and
      characterized using restriction enzymes. One of them, BQ31, was used to construct
      different sized probes labelled with digoxigenin-11-dUTP. These probes failed to
      hybridize with DNA of some insect parvoviruses and with DNA of a parvo-like virus
      of shrimp. They reacted strongly with dilutions of homogenized IHHNV-infected
      shrimp tissues and, conversely, did not react with uninfected shrimp tissues.
      They hybridized in situ, in sections of infected animals, labelling strongly the
      target cells and particularly the nuclear Cowdry type A inclusion body, which is
      the most diagnostic characteristics of this disease.

PMID- 8277270
TI  - High level expression in Escherichia coli cells and purification of poliovirus
      protein 2Apro.
AB  - The poliovirus protease 2Apro has been produced to high levels in Escherichia
      coli using the inducible system that utilizes T7 RNA polymerase. The protease
      coding sequences that contained an additional AUG to start translation were
      cloned in pET vectors. Synthesis of 2Apro was induced by IPTG or IPTG plus
      rifampicin, the levels of the protein made being higher when IPTG alone was used.
      The expression of the protein is not toxic for E. coli cells and can be readily
      visualized by Coomassie blue staining of total bacterial protein extracts
      separated in polyacrylamide gels. Centrifugation of the broken bacterial cells
      sediments more than 95% of the 2Apro synthesized at a 95% purity level after
      sarkosyl treatment. Antibodies raised against 2Apro in E. coli recognize a 16K
      protein in poliovirus-infected cells. In addition, 2Apro shows activity in trans
      as measured by the cleavage of p220 in HeLa cell extracts and by cleavage of a
      poliovirus protein substrate that contains the junction between the P1 and P2
      polypeptides.

PMID- 8277271
TI  - Identification of seven putative origins of Autographa californica multiple
      nucleocapsid nuclear polyhedrosis virus DNA replication.
AB  - Seven putative origins of DNA replication (oris) were identified and located on
      the genome of Autographa californica multiple nucleocapsid nuclear polyhedrosis
      virus (AcMNPV), when an improved infection-dependent replication assay was used.
      A threefold higher yield of amplified plasmid was achieved when an m.o.i. of 1
      was used (instead of 25), and another twofold increase was obtained when the
      interval between transfection and infection was extended from 5 to 24 h. Six of
      the putative oris were located in hr regions with homologous sequences. This
      suggests that all hrs in AcMNPV are bifunctional, i.e. have both ori and enhancer
      activity for transcription. In addition to the six hrs, the HindIII-K fragment of
      AcMNPV was also identified to carry a putative ori, although this fragment does
      not contain an hr region. However, the individual role of these seven oris during
      viral DNA replication, and whether they are all active simultaneously in vivo, is
      still unclear. The replication of an ori-containing plasmid starts at the same
      time (6 h post-infection) and proceeds at the same rate as viral DNA replication.
      A circular topology of ori-containing plasmids was a prerequisite for
      replication. Linear DNA, with an ori, did not replicate. Therefore, we suggest a
      theta structure or a rolling-circle as a model for baculovirus DNA replication.

PMID- 8277272
TI  - Mapping of linear B cell epitopes on capsid proteins of bovine papillomavirus:
      identification of three external type-restricted epitopes.
AB  - Immunodominant, conserved and type-restricted external epitopes of bovine
      papillomavirus (BPV) major (L1) capsid protein have been identified using BPV
      particles and synthetic peptides. Antisera to disrupted BPV-1 recognized BPV-1
      and BPV-2 particles in immune electron microscopy (IEM) studies and inhibited BPV
      2-induced focus formation of NIH/3T3 cells. Thus BPV-1/BPV-2 cross-reactive
      epitopes occur on the surface of virions. The L1 protein appeared to be
      immunodominant as the antisera reacted with three dominant BPV-1/BPV-2 conserved
      B cell epitopes (amino acids 111 to 125, 131 to 145 and 191 to 205) in Pepscan
      assays of BPV-1 L1, whereas no common epitopes and less frequent antibody binding
      to peptides were detected in Pepscans of the L2 protein of BPV-1. Four discrete
      variable regions were identified in the sequences of L1 proteins of BPV-1 and BPV
      2. Antisera against synthetic peptides corresponding to three of the four
      variable regions (amino acids 42 to 56, 435 to 449 and 485 to 499) of BPV-2 L1
      caused clumping of BPV-2, but not of BPV-1, particles as examined by IEM, and
      antisera to one peptide (amino acids 485 to 499) inhibited BPV-2-induced focus
      formation of NIH/3T3 cells. These data suggest that these regions are type
      specific BPV-2 L1 epitopes and that they occur on the virion surface. Although
      conformation-dependent epitopes remain to be identified on papillomaviruses, the
      linear epitopes identified in this study may be worthy of further study as
      constituents of experimental prophylactic vaccines.

PMID- 8277273
TI  - Modification of discrete nuclear domains induced by herpes simplex virus type 1
      immediate early gene 1 product (ICP0).
AB  - The outcome of herpes simplex virus type 1 (HSV-1) infection depends upon the
      interplay of both host and viral factors. During lytic infection, HSV-1 causes a
      loss of immunofluorescent staining of discrete nuclear domains (ND10). This
      elimination of the host's ND10 staining occurs under conditions that allow only
      HSV-1 immediate early viral gene expression. Western blot analysis indicates that
      the loss of ND10 staining is due to ND10 redistribution, rather than protein
      degradation or turnover. When deletion mutants of all of the HSV-1 immediate
      early genes were tested, only infection with an immediate early gene 1 product
      (ICP0) deletion mutant, d11403, was unable to eliminate ND10 antigen staining.
      Also, ICP0 transiently colocalized with ND10 antigens, after which ND10 antigens
      became undetectable. At late times during infection with d11403, the host ND10
      antigens were retained in virus-induced structures which were never observed
      during wild-type HSV-1 infection. These results suggested that ICP0 may be
      directly involved in the modification of the host nuclear domain. Infection with
      an adenovirus recombinant that expressed ICP0 demonstrated that in the absence of
      other HSV-1 proteins ICP0 was sufficient for the change in nuclear distribution
      of host antigens located at ND10. We postulate that the trans-activation function
      of ICP0 during viral replication may be mediated by replacing, modifying or
      reorganizing nuclear host factors.

PMID- 8277274
TI  - The human cytomegalovirus 86K immediate early (IE) 2 protein requires the basic
      region of the TATA-box binding protein (TBP) for binding, and interacts with TBP
      and transcription factor TFIIB via regions of IE2 required for transcriptional
      regulation.
AB  - The 86K immediate early (IE) 2 protein of human cytomegalovirus trans-activates a
      number of homologous and heterologous promoters, including the cellular promoter
      for the 70K heat-shock protein (hsp70), and the human immunodeficiency virus long
      terminal repeat. We have previously shown that IE2 trans-activates these two
      promoters in a TATA-dependent manner, and that IE2 is able to form a direct
      contact with TATA-box binding protein (TBP) in vitro. We now show that IE2 binds
      to the basic repeat region of TBP. In addition IE2 can contact a second general
      transcription factor, TFIIB. We have mapped the TBP- and TFIIB-binding regions
      within IE2 and show that these regions overlap, and also lie within parts of the
      protein previously identified as being required for the trans-activation and
      autoregulation functions of IE2.

PMID- 8277275
TI  - Quantitative determination of human cytomegalovirus target sequences in
      peripheral blood leukocytes by nested polymerase chain reaction and temperature
      gradient gel electrophoresis.
AB  - A competitive nested PCR-temperature gradient gel electrophoresis protocol
      (nPCR/TGGE) has been established for the quantification of human cytomegalovirus
      (HCMV) target sequences. The measurement was achieved by co-amplification of a
      defined copy number of an internal standard (st) and separation of st and wild
      type (wt) amplimers by temperature gradient gel electrophoresis (TGGE). The
      number of HCMV target sequences could be precisely determined within wt/st ratios
      of 0.1 to 10. With 50 copies of the st sequence the detection limit of nPCR/TGGE
      was found to be five to 10 copies of the target sequence. Effects of sample
      preparation on quantitative HCMV PCR were minimized by the additional
      quantification of beta-globin target sequences and calculation of the ratio of
      HCMV copies/beta-globin copies. Serial peripheral blood leukocyte specimens of 17
      renal allograft recipients positive in a qualitative nested HCMV PCR were tested
      using nPCR/TGGE. Thirty healthy blood donors served as negative controls.
      Positive results were obtained by nPCR/TGGE in nine renal allograft recipients
      but in none of the healthy blood donors. Five of five patients with an HCMV pp65
      antigenaemia and positive for HCMV IgM were positive in nPCR/TGGE. The highest
      HCMV/beta-globin ratios (10,000 to 8000 copies HCMV/10(6) copies beta-globin)
      were found in transplant recipients experiencing acute clinically symptomatic
      HCMV infection. HCMV DNA levels in asymptomatic patients ranged from 900 to 200
      copies HCMV/10(6) beta-globin.

PMID- 8277276
TI  - Susceptibility of transgenic tobacco plants expressing tobacco rattle virus coat
      protein to nematode-transmitted and mechanically inoculated tobacco rattle virus.
AB  - Transgenic Samsun NN tobacco plants expressing the coat protein of tobacco rattle
      virus were exposed to mechanical leaf inoculation with tobacco rattle virus and
      to viruliferous trichodorid vector nematodes. Whereas plants were resistant to
      mechanical inoculation the vector nematodes successfully transmitted tobacco
      rattle virus to the roots as well as to the leaves of these plants. It is
      suggested that transgenic resistance is overcome either because vector nematodes
      inject relatively large numbers of virus particles into a cell or because they
      inject destabilized particles. The results indicate that coat protein-mediated
      resistance is unlikely to be of value for controlling tobacco rattle virus in
      field crops.

PMID- 8277277
TI  - Replication of the DNA A component of African cassava mosaic virus in a
      heterologous system.
AB  - The capacity for autonomous replication of the DNA A of African cassava mosaic
      virus (ACMV), a member of the bipartite geminiviruses infecting dicotyledonous
      plants, has been compared in host and non-host cells. A derivative of the ACMV
      DNA A was transfected into tobacco and maize protoplasts. Although ACMV is not
      able to infect maize, replication of the DNA A in maize protoplasts was observed
      to occur. The efficiency of replication was 10 to 20% of that seen in tobacco
      protoplasts. In both plant systems, replication was detected after the onset of
      cell division. ACMV replication in maize cells was compared to that of wheat
      dwarf virus and found to be 10 to 20% of that observed with the monocotyledon
      specific virus. Insertion of 1165 bp of non-viral DNA into the ACMV DNA A
      prevented replication in maize but not in tobacco.

PMID- 8277278
TI  - Expression of potyvirus proteins in insect cells infected with a recombinant
      baculovirus.
AB  - The N-terminal portion (P1-HC-Pro-P3) of the tobacco vein mottling virus (TVMV)
      polyprotein was expressed in insect cells and larvae by a recombinant
      baculovirus. The proteases necessary to process this TVMV polyprotein fragment
      were active in insect cells, since mature P1, HC-Pro and P3 proteins were
      detected by specific antisera in Western blots. Antisera to P1, HC-Pro and P3
      also recognized polypeptides with apparent M(r) values predicted for the
      intermediate processing products of the polyprotein fragment. The results of this
      study indicate that the autocatalytic processing of TVMV HC-Pro from the
      polyprotein is supported by insect cells. Helper component activity in extracts
      of cells infected with recombinant baculovirus was not detected by aphid
      transmission assay.

PMID- 8277279
TI  - Mutations in zucchini yellow mosaic virus helper component protein associated
      with loss of aphid transmissibility.
AB  - Zucchini yellow mosaic virus (ZYMV) is a potyvirus transmitted by aphids in a non
      persistent manner. Isolates having partially or totally lost their ability to be
      transmitted by aphids have been isolated and found to be affected in their helper
      component activities. We have sequenced the helper component coding region of
      poorly aphid-transmissible (PAT) variants of two strains of ZYMV, E15 and R5A.
      Mutations have been identified at the nucleotide level leading to two amino acid
      changes in the E15 PAT variant helper component and to one amino acid change
      located in the cysteine-rich region (well-conserved among potyviruses) in R5A PAT
      variant helper component. The mutation in the R5A variant changes the same amino
      acid as the one identified in potato virus C, a non-transmissible strain of
      potato virus Y.

PMID- 8277280
TI  - Striking similarities between the nucleotide sequence and genome organization of
      citrus tatter leaf and apple stem grooving capilloviruses.
AB  - The sequence of the 3'-terminal 2956 nucleotides, excluding the poly(A) tail, of
      the citrus tatter leaf virus (CTLV) genome was determined and compared with that
      of the apple stem grooving virus (ASGV) genome. The sequence of the 3'-terminal
      region of CTLV contains two overlapping open reading frames (ORFs) and a 3'
      terminal non-coding region of 142 nucleotides. The long, incomplete ORF1 ends at
      UAG (position 2812) and encodes a protein with at least 938 amino acids (M(r) >
      108,703). This protein contains the GDD motif associated with the RNA polymerase.
      ORF2, in a different frame within ORF1, starts at AUG (position 1248) and stops
      at UGA (position 2208) encoding a protein with an M(r) of 36,179 (36K). Partial
      homologies were found among the 36K protein of CTLV, the 50K protein of apple
      chlorotic leaf spot closterovirus, the 40K protein of potato virus T and the gene
      1 products of caulimoviruses. The arrangement of ORFs in the 3'-terminal region
      of the CTLV genome is in perfect agreement with that of the ASGV genome. The
      sequence of the 3'-terminal 2956 nucleotides, excluding the poly(A) tail, of the
      CTLV genome shows 86.1% identity to that of the ASGV genome. Similarities of
      amino acid sequences encoded by ORF1 and ORF2 of CTLV with the corresponding
      regions of ASGV are 86.1% and 97.3%, respectively. These results indicate that
      CTLV is a capillovirus closely related to ASGV.

PMID- 8277281
TI  - Vibriophage D10 contains non-permuted DNA with cohesive ends.
AB  - Phage D10, a Vibrio cholerae O-1 El Tor group X phage, is one of the five newly
      isolated phages used in the phage typing scheme developed for V. cholerae O-1
      biotype El Tor and belongs to the Myoviridae family. From electron microscopic
      studies it is shown that phage D10 has a DNA genome of 32 +/- 0.2 kb. This is the
      first report where it has been shown by the construction of a partial
      denaturation map that this vibriophage genome is nonpermuted and has cohesive
      ends. The location of the ends of the DNA in the phage head has also been
      inferred.

PMID- 8277282
TI  - Co-replication of several isotypes of foot-and-mouth disease virus.
AB  - Genome segments of the foot-and-mouth disease virus isolates O1Lombardy and O3
      Venezuela that encode, among other products, capsid protein VP1 were amplified
      using PCR, and the products were cloned and sequenced. The alignment of up to 11
      O3-specific sequences revealed six silent nucleotide changes a well as six
      changes that cause amino acid substitutions in capsid protein VP1 at positions
      45, 83, 141, 145, 170 and 178. The heterogeneity of three O1-specific sequences
      consisted of seven silent exchanges and amino acid changes at positions 85 and
      134 on VP1. Amplification, subclonning and sequencing of cloned O3-specific cDNA
      was performed to examine the nature of the sequence heterogeneity. As no
      difference was found among five subcloned sequences, we conclude that the Taq
      polymerase copied the DNA correctly. The sequence heterogeneity observed with
      both virus isolates is, therefore, consistent with the quasispecies structure of
      foot-and-mouth disease virus. Furthermore, amino acid changes at a number of
      sites have been found to be involved in the formation or modulation of
      neutralizing epitopes. The novel aspect of this study is the ability to estimate,
      by cloning of PCR products, the number of virus isotypes, possibly varying in
      antigenicity, that are able to co-propagate. Seven isotypes of O3 Venezuela were
      identified. Some are of particular interest because they exhibit a change at VP1
      codon 145 that causes the replacement of arginine, possibly essential for virus
      attachment to cells, by isoleucine.

PMID- 8277283
TI  - HPLC is an effective and fast method for analysis of viral proteins: a study of
      encephalomyocarditis virus mutants differing in pathogenicity.
AB  - We investigated the use of HPLC in analysis of picornavirus variants by comparing
      structural polypeptides of three stable mutants of encephalomyocarditis virus
      (EMCV). The variants are known to differ in their pathogenicity for mice: plaque
      variant 2 (PV2) is diabetogenic, PV7 is non-diabetogenic and PV21 induces a
      generalized lethal infection. We first used HPLC to separate the structural
      proteins at high purity levels. Detailed analysis of these structural proteins by
      HPLC-peptide mapping revealed differences in all four viral proteins of PV21 as
      compared with mutants PV2 and PV7. A single amino acid exchange was found in
      viral protein 1 between PV2 and PV7. Altered peaks were identified by calculating
      retention times of tryptic peptides using sequence data and a computer program.
      Since peak alterations could be attributed to the observed amino acid exchanges,
      the results correlate well with cDNA sequencing data. Thus HPLC proved to be a
      useful and fast tool for primary or additional characterization of picornavirus
      variants at the level of whole virus proteins.

PMID- 8277284
TI  - Molecular epidemiology of dengue 3 viruses and genetic relatedness among dengue 3
      strains isolated from patients with mild or severe form of dengue fever in French
      Polynesia.
AB  - The nucleotide sequences of a short fragment of the envelope protein gene
      encoding amino acids 25 to 89 of 27 dengue 3 viruses were determined by direct
      sequencing of PCR-amplified products, and the viruses were compared regarding
      their time of isolation and geographic distribution. Four distinct genotypic
      groups were discerned at 6% divergence between nucleotide sequences. The first
      group contained isolates from the South Pacific (1988 to 1992), Singapore (1973)
      and Indonesia (1973 to 1991). The second group comprised viruses from Asia (1956
      to 1989) including the reference strain H-87. The third was composed of one
      isolate from Thailand (1971), and the fourth included the early strains from
      French Polynesia (1964 to 1969) and from Puerto Rico (1963). Furthermore, the
      difference between early and recent strains from the South Pacific was as high as
      12.3%. This observation suggests that the recent epidemics in the South Pacific
      were probably the consequence of the spread of a new variant that emerged from
      New Caledonia. However, relatedness between nucleotide sequence and disease
      severity, or between strains from epidemics with mild disease (New Caledonia) and
      strains from epidemics with severe disease (French Polynesia) could not be
      demonstrated.

PMID- 8277285
TI  - A new serotype of the outer capsid protein VP4 shared by an unusual human
      rotavirus strain Ro1845 and canine rotaviruses.
AB  - The VP4 protein of human rotavirus (HRV) strain Ro1845 and canine rotavirus
      strains K9 and CU-1 exhibited greater than 98% amino acid identity within their
      group, but showed less identity with VP4 proteins of other HRV and animal
      rotavirus strains, the simian rotavirus strain RRV VP4 being most similar to them
      (90% amino acid identity). To exclude the possibility that these three strains
      were members of the RRV VP4 serotype P3, neutralization studies were performed
      using antisera to reassortant viruses containing the VP4 gene from each of
      Ro1845, CU-1 and RRV. The result established close antigenic similarity among the
      VP4 proteins of Ro1845, K9 and CU-1 and revealed only a marginal degree of
      similarity between the VP4 proteins of these three strains and that of strain
      RRV. These sequence and serological data suggest that the VP4 proteins of Ro1845,
      K9 and CU-1 represent a new P serotype which we propose to assign P13.

PMID- 8277286
TI  - Evidence for different lineages of rinderpest virus reflecting their geographic
      isolation.
AB  - Sequence analysis of part of the fusion protein gene from recent isolates of
      rinderpest virus revealed that distinct lineages of the virus exist which reflect
      the geographical location of their isolation in Africa and Asia. Current strains
      circulating in Kenya and Sudan were most similar, both in terms of nucleotide
      sequence and pathogenic nature, to viruses isolated in Egypt and in Nigeria in
      1983/1984 and they were quite distinct from an East African isolate (RBT-1) from
      the 1960s. Two older isolates of the virus, the Japanese avianized/lapinized
      vaccine strain dating from the 1930s and the Old Kabete strain dating from 1911,
      each differed considerably from the other viruses. The sequence data were derived
      from the region where the precursor protein is cleaved to yield the biologically
      active F1/F2 heterodimer; all strains analysed had a highly basic connecting
      peptide which is required for efficient cleavage by endogenous host cell
      proteases. No correlation was found between amino acid changes at this site and
      the rinderpest virus pathogenicity unlike the association reported for Newcastle
      disease virus.

PMID- 8277287
TI  - Comparative analysis of the immunoprotective abilities of glycosylated and
      deglycosylated parainfluenza virus type 3 surface glycoproteins.
AB  - The role of carbohydrate moieties on the immunoprotective ability of
      parainfluenza virus type 3 (PIV-3) haemagglutinin-neuraminidase (HN) and fusion
      (F) glycoproteins was tested in hamsters. HN and F proteins were purified from
      detergent-solubilized virus by lentil-lectin affinity chromatography and
      deglycosylated by treatment with endoglycosidase F (endo F). Immunization of
      hamsters with either 1 or 5 micrograms of mock-treated (glycosylated) affinity
      purified proteins elicited strong haemagglutination inhibition and neutralizing
      antibody responses 4 weeks after the primary injection. In contrast, titres were
      significantly lower with endo F-treated (deglycosylated) proteins. However,
      following the booster doses with at least 5 micrograms of antigen, glycosylated
      and deglycosylated proteins induced comparable antibody titres. There was no
      significant difference in the ability of the glycosylated or deglycosylated
      proteins to protect either the upper or lower respiratory tracts of immunized
      hamsters against PIV-3 challenge. These results suggest that the carbohydrate
      moieties of the HN and F proteins are not necessary for eliciting a protective
      response in hamsters.

PMID- 8277288
TI  - Analysis of the ovine respiratory syncytial virus (RSV) G glycoprotein gene
      defines a subgroup of ungulate RSV.
AB  - Respiratory syncytial virus (RSV) has been isolated from sheep suffering from
      respiratory tract disease. Since the greatest differences between bovine RSV and
      human RSV are found on the attachment G protein, we have determined the
      nucleotide and deduced amino acid sequences of the G gene of ovine RSV. The
      latter contained 838 nucleotides and had a major open reading frame encoding a
      protein of 263 residues, and shared 73% nucleotide sequence identity with that of
      bovine RSV. The deduced amino acid sequence of the ovine RSV G protein showed
      only 60% amino acid identity with the G protein of bovine RSV. Despite the low
      level of identity, there were similarities in the predicted hydropathy profiles
      of the G proteins of ovine and bovine RSV. The intergenic sequences for the SH-G
      and G-F gene junctions of ovine RSV showed 64 and 57% identity respectively with
      the corresponding regions of the bovine RSV. Our results indicate that ovine and
      bovine RSV might be classified as two subgroups of an ungulate RSV.

PMID- 8277289
TI  - Isolation and immunogenic properties of a monomeric form of the HA1 subunit of
      the influenza virus haemagglutinin from infected cells.
AB  - A monomeric, truncated form of the HA1 subunit of the haemagglutinin of fowl
      plague virus can be isolated from chorioallantoic membranes of infected eggs.
      This type of soluble HA1 seems to be generated by the elimination of the amino
      terminal 19 amino acids from the native HA1, including the disulphide linkage to
      the HA2 subunit. The same type of truncated HA1 could be isolated from a filtrate
      of the allantoic fluid of infected embryonated eggs. Antibodies prepared against
      this monomeric soluble form of HA1 did not inhibit haemagglutination or
      neutralize viral infectivity, but interfered with virus release and would be
      expected to impair the spread of virus after infection.

PMID- 8277290
TI  - Sequence analysis of human T cell lymphotropic virus type I strains from southern
      India: gene amplification and direct sequencing from whole blood blotted onto
      filter paper.
AB  - Human T cell lymphotropic virus type I (HTLV-I) infection in India has been found
      to be associated with adult T cell leukaemia/lymphoma (ATLL) and HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP) among life-long
      residents of southern India. To examine the heterogeneity of HTLV-I strains from
      southern India and to determine their relationship with the sequence variants of
      HTLV-I from Melanesia, 1149 nucleotides spanning selected regions of the HTLV-I
      gag, pol, env and pX genes were amplified and directly sequenced from DNA
      extracted from whole blood blotted onto filter paper and from peripheral blood
      mononuclear cells, obtained from one patient with HAM/TSP, two with ATLL and
      eight asymptomatic carriers from Andhra Pradesh, Kerala and Tamil Nadu. Sequence
      alignments and comparisons indicated that the 11 HTLV-I strains from southern
      India were 99.2% to 100% identical among themselves and 98.7% to 100% identical
      to the Japanese prototype HTLV-I ATK. The majority of base substitutions were
      transitions and silent. No frameshifts, insertions, deletions or possibly disease
      specific base changes were found in the regions sequenced. The observed
      clustering of the Indian HTLV-I strains with those from Japan, as determined by
      the maximum parsimony method, suggested a common source of HTLV-I infection with
      subsequent parallel evolution. Amplification of DNA from blood specimens
      collected on filter paper may be useful for the study of other blood-borne
      pathogens.

PMID- 8277291
TI  - Characterization of vaccinia virus gene B12R.
AB  - We report the characterization of vaccinia virus gene B12R which is predicted to
      encode a 33K protein with 36% amino acid identity to the serine/threonine protein
      kinase encoded by vaccinia virus gene B1R. S1 nuclease protection experiments
      showed that gene B12R is transcribed early during infection from an initiation
      site 11 bp upstream of the open reading frame (ORF). The gene encodes a 33K
      polypeptide that is not required for virus replication in tissue culture nor for
      virus virulence in a murine intranasal model. Expression of the B12R gene in
      Escherichia coli produced an abundant 33K polypeptide which lacked protein kinase
      activity under conditions in which the protein kinases encoded by vaccinia virus
      gene B1R and African swine fever virus gene j9L are active.

PMID- 8277292
TI  - Analysis of protective immune responses to the glycoprotein H-glycoprotein L
      complex of herpes simplex virus type 1.
AB  - A recombinant vaccinia virus expressing both glycoprotein H (gH) and glycoprotein
      L (gL) of herpes simplex virus type 1 (HSV-1) was used to examine the protective
      response to gH-gL in immunized mice and to compare these responses with those
      induced by the highly protective immunogen, glycoprotein D (gD). Weak levels of
      HSV-1-specific neutralizing antibody were obtained in response to the gH-gL
      complex, virus clearance from the site of challenge was marginally enhanced
      compared to that observed following immunization with gH alone, and gH-gL was
      found to protect mice against acute infection in the ganglia, although not as
      efficiently as gD.

PMID- 8277293
TI  - Human adenovirus type 5 recombinants expressing simian immunodeficiency virus
      macaque strain gag antigens.
AB  - The p55 gag gene of simian immunodeficiency virus macaque strain (SIVmac) and the
      core p27 gag component linked to a synthetic AUG codon have been cloned into
      adenovirus type 5 vectors to generate either viable E3-replacement or defective
      E1-replacement viruses. The viruses express the expected SIV proteins in both
      human and, for the non-defective viruses, monkey cells. A considerable proportion
      of the p55 produced is exported from the infected cell. These viruses should
      prove useful both in studies of the immune response to SIV and as components of
      candidate vaccines aimed specifically at provoking cytotoxic T cell responses.

PMID- 8277294
TI  - Sequence analysis of bovine adenovirus type 3 early region 3 and fibre protein
      genes.

PMID- 8277295
TI  - Pretreatment variables that predict completion of an adolescent substance abuse
      treatment program.
AB  - The present study was designed to determine the utility of pretreatment data in
      predicting completion and dropout from adolescent substance abuse treatment. One
      hundred thirty-two consecutively admitted adolescents (mean age = 16.4 years; 93
      male subjects, 39 female subjects) with significant substance abuse were
      administered a battery of standardized substance abuse, psychopathology, and
      social questionnaires immediately after admission to an intensive, set-length
      substance abuse treatment program. Seventy-four adolescents completed the
      program. Using discriminant function analyses, five pretreatment measures were
      found to predict treatment completion in male subjects, including: greater
      severity of problems with alcohol; greater use of drugs other than alcohol,
      cannabis, and tobacco; higher degree of internalizing problems; and lower self
      esteem. Significant predictors for completion by female subjects were not found.
      The role of treatment readiness and motivation for male subjects is examined, and
      the lack of significant findings for female subjects is discussed.

PMID- 8277296
TI  - Eliciting psychotic symptoms using a semi-structured diagnostic interview. The
      importance of collateral sources of information in a first-admission sample.
AB  - This study addressed the importance of medical record information in determining
      the presence of psychotic symptoms in first-admission patients. A sample of 232
      first-admission inpatients screened for psychotic symptoms by facility personnel
      was administered the Structured Clinical Interview for DSM-III-R (SCID) followed
      by a medical record review and interview with a significant other. Medical
      records were unavailable for sixteen patients. These patients were more often
      female, married, and more suspicious than patients whose records were reviewed.
      Of those having interviews and record reviews, 49 showed no clear evidence of
      psychosis. The remainder were divided into three groups: 97 subjects who revealed
      all of their psychotic symptoms during the interview (SCID-ALL); 61 who revealed
      only some of their delusions or hallucinations during the interview (SCID-PART);
      and 25 who revealed none of this information during the interview but whose
      records clearly described psychosis (SCID-NONE). The three groups were reasonably
      similar demographically and with respect to clinical history. Clinically, at the
      time of interview, SCID-NONE subjects were less often still psychotic, were rated
      on the Brief Psychiatric Rating Scale as less depressed, more withdrawn, less
      cooperative and less severely ill, and had poorer insight ratings on the Hamilton
      Depression Scale.

PMID- 8277297
TI  - The inventory for deja vu experiences assessment. Development, utility,
      reliability, and validity.
AB  - In this article the development, utility, reliability, and validity of the
      Inventory for Deja vu Experiences Assessment (IDEA) are described. The IDEA is a
      23-item self-administered questionnaire consisting of a general section of nine
      questions and qualitative section of 14 questions. The latter questions comprise
      48 topics. The questionnaire appeared to be a user-friendly instrument with
      satisfactory to good reliability and validity. The IDEA permits the study of
      quantitative and qualitative characteristics of deja vu experiences.

PMID- 8277298
TI  - Suicide risk and violence risk in alcoholics. Predictors of aggressive risk.
AB  - The purposes of the study were: a) to examine whether risk for suicide and risk
      for violence were positively or negatively correlated; and b) to investigate
      potential predictors/mediators of suicide risk alone, violence risk alone, and
      risk for both suicide and violence. Suicide risk and violence risk were
      considered outcome variables. The predictor/mediator variables were eight ego
      defense mechanisms and 13 dysfunctional personality styles (both have been linked
      to aggressive risk). Seventy-four male alcoholics were administered questionnaire
      measures of suicide risk and violence risk, defenses, and disordered personality
      functioning. Results indicated that suicide and violence risk were significantly
      positively correlated. Three sets of predictor/mediator variables were
      identified: those predicting violence risk alone, those predicting suicide risk
      alone, and those predicting combined aggressive risk (risk for both suicide and
      violence). Connections obtained between predictor/mediator variables and outcome
      variables were explained in the context of existent clinical theory.

PMID- 8277299
TI  - Differentiation of dementia and depression by memory tests. A meta-analysis.
AB  - The many tasks used for clinical memory assessment have not been compared
      systematically for their usefulness in differentiating dementia and depression in
      old age. The aim of this meta-analysis was to identify those attributes of memory
      tasks that show high discriminative power. Eighty-nine effect-sizes were
      calculated out of 16 publications directly comparing demented and depressed
      patients. Outliers in the effect-size distribution (5% of the highest values)
      were excluded. The groups could be significantly better differentiated by delayed
      retrieval tasks rather than immediate retrieval tasks. Tasks with distraction
      before retrieval reached higher effect sizes than retrieval tasks without
      distraction. Tasks of high-capacity demand differentiated the groups
      significantly better than tasks of moderate and low demand. Effect-size magnitude
      was not influenced by patient characteristics except severity of dementia. Thus,
      demented and depressed patients may best be differentiated by a memory task that
      uses delayed retrieval with distraction.

PMID- 8277300
TI  - Marital support and remission of treated depression. A prospective pilot study of
      mothers of infants and toddlers.
AB  - Eighteen married mothers of infants and toddlers were evaluated before and after
      12 weeks of antidepressant treatment for major depressive disorder. The women
      were assessed at baseline on Snyder's marital disaffection and disharmony
      subscales and on selected clinical measures to evaluate these factors as
      correlates of remission. Remission was defined as a Hamilton Rating Scale for
      Depression score < or = 7 at week 12. Twelve women remitted; six did not.
      Nonremitted women reported high disaffection toward their husband, were in an
      episode of which the onset was not childbirth related (i.e., onset not within 3
      months after giving birth), or their youngest child was older than 6 months.
      Results showed that initial symptom severity was no different for the nonremitted
      and remitted women. Thus, the relationships between low disaffection, late onset,
      and not having a child under 6 months and nonremission appear to be independent
      of initial severity of depressive symptoms.

PMID- 8277301
TI  - Dysfunctional attitudes in major depression. Changes with pharmacotherapy.
AB  - High levels of dysfunctional attitudes have been associated with greater severity
      of depression and poorer response to pharmacological treatment. The goal of our
      study was to examine this relationship and the changes in dysfunctional attitudes
      after treatment with fluoxetine, a relatively selective serotonin uptake
      inhibitor. Dysfunctional attitudes were evaluated with both the Cognitions
      Questionnaire (CQ) and the Dysfunctional Attitudes Scale (DAS) in 115 outpatients
      diagnosed as having major depressive disorder. After 8 weeks of treatment with
      fluoxetine, 67 of these patients again completed the DAS and the CQ.
      Dysfunctional attitudes were associated with depression severity both before and
      after treatment and decreased linearly with treatment of the depression. Negative
      thinking and dysfunctional attitudes, as measured by both DAS and CQ, were not
      predictive of the degree of improvement in depressive symptoms. These findings
      partly support a state-dependent interpretation of dysfunctional attitudes, and
      provide evidence of significant reductions in these attitudes after treatment
      with a serotonin uptake inhibitor.

PMID- 8277302
TI  - Explaining attitudes toward medication compliance among a seriously mentally ill
      population.
AB  - Data from a clinical trial of consumer-delivered case management services were
      used to construct an explanatory model for attitudes toward medication
      compliance, focusing on psychosocial factors. A regression model explaining
      attitudes toward medication compliance shows that more positive attitudes toward
      compliance are related to older age, fewer symptoms, and a broader array of daily
      activities involving social relations. Participation in social activities is a
      practical goal of psychosocial rehabilitation services that support compliance
      with medication regimens and psychiatric treatment.

PMID- 8277303
TI  - Panic induced by lactate infusion during electroconvulsive therapy?

PMID- 8277304
TI  - Commentary on positive associations between dichotic listening errors, complex
      partial epileptic-like signs, and paranormal beliefs.

PMID- 8277305
TI  - Clinical predictors of self-mutilation in hospitalized forensic patients.
AB  - This study evaluated the clinical correlates and inpatient course of self
      mutilation in a diagnostically diverse sample of hospitalized forensic patients.
      Fifty-three male forensic inpatients, treated in a maximum-security hospital, who
      engaged in at least one instance of self-mutilation during a 2-year period, were
      studied and compared with 50 male forensic patients at the same hospital who had
      not engaged in self-mutilation. Self-mutilating patients were younger, more
      likely to carry a diagnosis of personality disorder or mental retardation,
      engaged in more outwardly directed aggressive behavior as assessed by the Overt
      Aggression Scale, were treated with substantially higher doses of neuroleptics,
      and were more likely to be civil or correctional patients than insanity
      acquittees. The two groups did not differ on variables such as history of
      suicide, history of violence, neurological characteristics, and other demographic
      variables. After an incident of self-mutilation, the probability of recurrence
      was high. The substantially higher level of outwardly directed aggression of self
      mutilating patients, along with their higher apparent need for neuroleptization
      and the high risk of recurrence of the self-mutilation, suggest that they are a
      subset of violent individuals who are relatively unresponsive to treatment and
      who are dangerous to self and others.

PMID- 8277306
TI  - Characterization of three new triterpenoid saponins from Ardisia japonica.
AB  - The isolation and characterization of three novel triterpene glycosides 1-3 from
      the medicinal plant Ardisia japonica (Myrsinaceae) are described. The compounds
      are characterized by a branched oligosaccharide chain, composed of four sugar
      units. The oligosaccharide structures were determined by 1H-1H correlation
      spectroscopy (COSY, HOHAHA, ROESY) and 1H-13C heteronuclear correlation (HETCOR)
      nmr experiments. The aglycone moieties are the oleane-type triterpenes
      cyclamiretin A for 1 and the new 13,28-epoxy-30,30-dimethoxyolean-3 beta, 16
      alpha-diol and 3 beta, 16 alpha-dihydroxy-13,28-epoxyolean-29-oic acid for 2 and
      3, respectively.

PMID- 8277307
TI  - Further lupane lactones from Kokoona ochracea.
AB  - Additional new lupane lactones were isolated from the stem bark of Kokoona
      ochracea (Celastraceae). Their structures have been elucidated, through the
      application of 1D and 2D nmr spectroscopic methods, as 20,29-dihydroxy-3-oxolupan
      30,21 alpha-olide (ochraceolide D) [1] and 28-hydroxy-3-oxolup-20(29)-en-30,21
      alpha-olide (ochraceolide E) [2]. These compounds and the mono- and di-acetates
      of ochraceolide D (4 and 5, respectively) were evaluated for in vitro cytotoxic
      activity against P-388 murine lymphocytic leukemia cells and a panel of human
      cancer cell systems. Ochraceolide D [1] was significantly cytotoxic (ED50, 3.9
      micrograms/ml) against human glioblastoma (U373) cells. Other compounds (4, 5,
      and 2) exhibited only a weak cytotoxic response in certain cancer cell lines.

PMID- 8277308
TI  - Antineoplastic agents, 256. Cell growth inhibitory isocarbostyrils from
      Hymenocallis.
AB  - The bulbs of Hymenocallis littoralis, collected in Hawaii and horticulturally
      grown in Arizona, and bulbs of Hymenocallis caribaea and Hymenocallis latifolia,
      collected in Singapore, were found to contain a cytotoxic, isocarbostyril-type
      biosynthetic product, 7-deoxy-trans-dihydronarciclasine [2]. This new compound
      inhibited the cytopathicity and/or replication of various viruses. Companion
      cytotoxic constituents of H. littoralis and Hymenocallis sp. were found to be
      pancratistatin [1], narciclasine [5], and 7-deoxynarciclasine [4]. These four
      compounds, along with four other closely related compounds, were comparatively
      evaluated in the National Cancer Institute's in vitro cytotoxicity panel.
      Although there were striking differences in overall potency, some of the
      compounds shared a highly characteristic differential cytotoxicity profile
      against the 60 diverse human tumor cell lines comprising the NCI panel. As a
      group, the melanoma subpanel lines were most sensitive; certain individual lines
      within other subpanels (eg., NSC lung, colon, brain, renal) were as much as a
      thousand-fold or more sensitive than the less sensitive lines.

PMID- 8277309
TI  - Studies on the acetogenins of Formosan annonaceous plants. II. Cytotoxic
      acetogenins from Annona reticulata.
AB  - Using cytotoxicity as a guide to fractionation, one novel acetogenin,
      annoreticuin-9-one [3], and four known cytotoxic acetogenins, squamone [4],
      solamin [5], annomonicin [6] and rolliniastatin 2 [7], were isolated from active
      extracts of the leaves of the Formosan plant Annona reticulata. Their structures
      were elucidated on the basis of uv, ir, 1H- and 13C-nmr, and ms data of the
      natural compounds and their derivatives.

PMID- 8277310
TI  - Defensive secretion of the millipede Floridobolus penneri.
AB  - Six quinones were identified from the defensive secretion of the millipede
      Floridobolus penneri. The two major components, 2-methyl-1,4-benzoquinone [1] and
      2-methoxy-3-methyl-1,4-benzoquinone [3], previously characterized, comprise 95%
      of the secretion. One of the minor compounds, 2,5-dimethyl-3-methoxy-1,4
      benzoquinone [4], is a new natural product. Another, 2-hydroxy-3-methyl-1,4
      benzoquinone [2], had been tentatively characterized from a microbial source. The
      other two components are 2,3-dimethoxy-1,4-benzoquinone [5] and 2,3-dimethoxy-5
      methyl-1,4-benzoquinone [6]. No sex difference in the composition of the
      secretion was noted.

PMID- 8277311
TI  - Two new cytotoxic chalcones from Calythropsis aurea.
AB  - The crude extract of Calythropsis aurea (Myrtaceae) produced a pattern of
      differential cytotoxicity in the NCI 60 cell line assay which was similar to
      those of known tubulin-interactive compounds. Cytotoxicity-guided fractionation
      led to the isolation of two new chalcones, calythropsin [1] and
      dihydrocalythropsin [2], which were responsible for the activity. Calythropsin
      was demonstrated to have a weak effect on mitosis, and presumably also on tubulin
      polymerization.

PMID- 8277312
TI  - Cytotoxic constituents from Hyptis verticillata.
AB  - A new cytotoxic (P-388 ED50 4 microgm/ml) arylnaphthalene lignan has been
      isolated from the Mexican medicinal plant Hyptis verticillata (Lamiaceae) and
      characterized as 5-methoxydehydropodophyllotoxin [1]. Eight additional lignans
      were also obtained by bioactivity-directed fractionation using the brine shrimp
      lethality test. Of these, the dehydro-beta-peltatin methyl ether 2 (P-388 ED50
      1.8 microgm/ml) is reported for the first time as a natural product isolate. The
      other bioactive compounds were identified as dehydropodophyllotoxin [3],
      deoxydehydropodophyllotoxin [4]. (--)-yatein [5], 4'-demethyldeoxypodophyllotixin
      [6], isodeoxypodophyllotoxin [7], deoxypicropodophyllin [8], and beta
      apopicropodophyllin [9]. Each of these compounds was evaluated against a panel of
      cell lines comprising a number of human cancer cell types [breast, colon,
      fibrosarcoma, lung, prostate, KB, and KB-VI (a multi-drug resistant cell line
      derived from KB)] and murine lymphocytic leukemia (P-388). Lignans 1-4 showed
      marginal cytotoxic activity against the human cell lines tested. In contrast,
      compounds 5-9 demonstrated a general nonspecific activity comparable to that of
      podophyllotoxin [12] (ED50 < 10-2 microgm/ml). In addition, the antimitotic
      potential of these compounds was determined in the astrocytoma (ASK) assay.
      Finally, the plant was also shown to contain the flavonoid sideritoflavone (KB
      ED50 1.6 microgm/ml) and the known pentacyclic triterpenoids ursolic, maslinic, 2
      alpha-hydroxyursolic and oleanolic acids.

PMID- 8277313
TI  - Use of alkenylresorcinols from Ononis speciosa as synthetic precursors of
      compounds with potential biological activity.
AB  - Selective ozonization of the alkenylresorcinols isolated from Ononis speciosa was
      studied. The derivatives thus obtained were used as precursors in the synthesis
      of cannabinoids and macrocyclic lactones.

PMID- 8277314
TI  - Cytotoxic diterpenoids from the brown alga Dilophus ligulatus.
AB  - A new xenicane-type diterpene, dilopholide [5], and four known diterpenoids,
      acetoxycrenulide [1], acetylcoriacenone [2], and its epimer isoacetylcoriacenone
      [3], and hydroxyacetyldictyolal [4], have been isolated from the brown alga
      Dilophus ligulatus [syn. spiralis (Montagne) Hamel]. The structure of dilopholide
      [5] was elucidated by spectroscopic methods, including the concerted application
      of a number of 2D nmr techniques, including 1H-1H COSY, heteronuclear proton
      carbon chemical shift correlation (HETCOSY), and long-range HETCOSY. The
      cytotoxic activity of compounds 1-5 has been examined against several types of
      mammalian cells: human nasopharynx carcinoma cells (KB), human lung carcinoma
      cells (NSCLC-N6), murine leukemia cells (P-388), and murine leukemia cells
      expressing the multi-drug-resistance gene, mdr (P-388/DOX).

PMID- 8277315
TI  - New norcucurbitacin and heptanorcucurbitacin glucosides from Fevillea trilobata.
AB  - From the MeOH extract of the seeds of Fevillea trilobata (Cucurbitaceae) were
      isolated fevicordin A glucoside [1], cayaponoside B [2], cayaponoside D [3], a
      new norcucurbitacin glucoside, and a new heptanorcucurbitacin glucoside. The
      structure of the new norcucurbitacin glucoside, andirobicin A glucoside, was
      established as 29-nor-1,2,3,4,5,10-dehydro-25-methoxy-2-O-beta-D-glucopyranosyl-
      3,16 alpha,20R,22 xi-tetrahydroxy-11-oxocucurbit-23-ene [4], and that of the
      novel heptanorcucurbitacin glucoside, andirobicin B glucoside, as
      22,23,24,25,26,27,29-heptanor-1,2,3,4,5,10-dehydro-2-O-beta-D-g luc opyranosyl
      3,16 alpha-dihydroxycucurbita-11,20-dione [5].

PMID- 8277316
TI  - Starfish saponins, Part 51. Steroidal oligoglycosides from the starfish
      Distolasterias nipon.
AB  - A reinvestigation of the extracts from the starfish Distolasterias nipon,
      collected at Mutsu Bay, Japan, has led to the isolation of six glycosides of
      polyhydroxysteroids and six asterosaponins. Four steroidal glycosides have been
      identified as distolasterosides D1 [1] and D2 [2] (previously isolated from the
      same organism), and pycnopodioside C [5] and pisasteroside A [6], previously
      found in the related species Pycnopodia helianthoides and Pisaster ochraceus
      (family Asteridae), respectively. Two asterosaponins have been identified as the
      common versicoside A [7] and thornasteroside A [7a]. The two remaining glycosides
      of polyhydroxysteroids, named distolasterosides D4 [3] and D5 [4], and four
      asterosaponins designated nipoglycosides A [8], B [9], C [10], and D [11] are new
      compounds, and their structures have been elucidated mainly by interpretation of
      spectral data and comparison with known compounds.

PMID- 8277317
TI  - Antifungal metabolites from Trichoderma harzianum.
AB  - A detailed examination of the metabolites produced in liquid cultures by a strain
      of Trichoderma harzianum, isolated from wheat roots, has resulted in the
      identification of a further five metabolites. Two of these, cyclonerodiol [5] and
      the octaketide keto diol 6, have previously been isolated from a strain of
      Trichoderma koningii. The structures of the three new octaketide-derived
      compounds 7, 8, and 10 have been deduced from spectroscopic and chemical studies.
      All newly isolated compounds show antibiotic activity towards the take-all
      fungus, Gaeumannomyces graminis var. tritici.

PMID- 8277318
TI  - Kinase inhibitors from Polygonum cuspidatum.
AB  - Bioassay-directed fractionation of a medicinal plant, Polygonum cuspidatum
      (Polygonaceae), has led to the discovery of a hydroxystilbene, resveratrol [1],
      as an inhibitor of a protein-tyrosine kinase (p56lck) partially purified from
      bovine thymus. Both trans and cis isomers of resveratrol possess comparable
      protein-tyrosine kinase inhibitory activity. Comparison of the IC50 values of
      resveratrol for protein-tyrosine kinase inhibitory activity with those of piceid
      (resveratrol-O3-beta-glucoside) [2] and resveratrol-O4'-beta-glucoside [3] shows
      the requirement of free hydroxyl groups on both phenyl rings for the protein
      tyrosine kinase inhibition. Protein kinase C inhibitory analysis suggests the
      requirements of two free hydroxyl groups on one phenyl ring only.

PMID- 8277319
TI  - Pantherinine, a cytotoxic aromatic alkaloid, and 7-deazainosine from the ascidian
      Aplidium pantherinum.
AB  - A new cytotoxic aromatic alkaloid, pantherinine [1], and a mixture of nucleosides
      including 7-deazainosine [3], have been isolated from the ascidian Aplidium
      pantherinum collected at Stenhouse Bay, South Australia. The structures were
      determined primarily from 1H- and 13C-nmr data, especially one-bond and multiple
      bond proton-carbon correlations. Although 7-deazainosine [3] has been known as a
      synthetic compound for several decades, this appears to be the first report of
      its isolation as a natural product.

PMID- 8277320
TI  - Sesquiterpene glycosides from Calendula arvensis.
AB  - The extract of the aerial parts of Calendula arvensis afforded four new
      sesquiterpene glycosides 1-4 in addition to three known compounds. The structures
      of the new compounds were established by high field 1H-nmr spectroscopy.

PMID- 8277321
TI  - A cytotoxic beta-carboline from the bryozoan Catenicella cribraria.
AB  - 1-Vinyl-8-hydroxy-beta-carboline was identified as the cytotoxic constituent of
      the bryozoans Catenicella cribraria and Cribricellina cribraria. Literature nmr
      data for this previously known compound, now reported from a new source, were
      corrected.

PMID- 8277322
TI  - Three new cytotoxic metabolites from the marine sponge Plakortis
      halichondrioides.
AB  - Three new cytotoxic compounds, one a cyclic-peroxide-containing acid (5) and the
      two others alkylated dihydroxy alpha,beta-unsaturated C22 and C21 acids (6 and
      7), were isolated from the marine sponge Plakortis halichondrioides, which was
      collected off the coast of Jamaica. The structures were elucidated through mass
      and mainly 1D and 2D nmr spectral analysis. All three acids are cytotoxic against
      P-388 murine leukemia.

PMID- 8277323
TI  - Two bioactive pterocarpans from Erythrina burana.
AB  - Bioactivity-directed fractionation of the CHCl3 extract of the bark of Erythrina
      burana afforded phaseollidin [1] and cristacarpin [2]. Both 1 and 2 exhibited
      moderate but selective activity towards DNA repair-deficient yeast mutants,
      whereas only 1 was found to be cytotoxic. 13C-nmr spectra of both compounds were
      assigned.

PMID- 8277324
TI  - Identification of novel iso/anteiso nonacosadienoic acids from the phospholipids
      of the sponges Chondrosia remiformis and Myrmekioderma styx.
AB  - The previously unreported 27-methyl-5,9-octacosadienoic acid [1] and 26-methyl
      5,9-octacosadienoic acid [2] were identified in the phospholipids of the
      Caribbean sponges Chondrosia remiformis and Myrmekioderma styx. Both sponges also
      contain the novel 15-methyl-5,9-hexadecadienoic acid [3] in their phospholipids.
      These results extend the possible chain lengths in delta 5,9 iso/anteiso fatty
      acids in sponge phospholipids from C17 to C29.

PMID- 8277325
TI  - Probabilistic diagnosis of normal pressure hydrocephalus and other treatable
      cerebral lesions in dementia.
AB  - Clinical profiles of dementia patients, differing with respect to age, presence
      of gait abnormalities and urinary incontinence are discussed. Epidemiological
      data, subjective probabilities and clinical reasoning are used to predict a
      treatable cerebral lesion, i.e., an intracranial space occupying lesion or normal
      pressure hydrocephalus (NPH). Our calculations help in distinguishing clinically
      between demented patients who are, and who are not likely to benefit from
      computed tomography (CT) investigation for treatable lesions and, eventually,
      from cerebrospinal fluid shunting for NPH. Utility calculations show that
      shunting can be recommended only for a patient with the full triad of symptoms of
      NPH, and CT evidence of NPH, when no other prognostic information is available.
      Future clinical research should address the long-term prognosis of (treated) NPH
      patients, and the mortality of shunting, because these two factors are critical
      to the shunting decision.

PMID- 8277326
TI  - Metabolic and cognitive changes in hereditary ataxia.
AB  - Fourteen subjects (affected, n = 7; at risk, n = 7) from one well-known kindred
      with adult onset autosomal dominant olivopontocerebellar atrophy (OPCA), were
      studied with [18F]-2-deoxy-D-glucose (FDG) positron emission tomography (PET),
      magnetic resonance imaging (MRI), cognitive testing and scored neurological
      examination, and compared with normal controls. The neurological examination, MRI
      and cognitive tests showed no significant differences between at risk and normal
      control subjects. Mild cognitive deficits were seen in affected subjects; the
      degree of cognitive change appeared to relate to the severity of the illness. MRI
      demonstrated cerebellar and brainstem atrophy in all affected subjects. PET
      studies showed higher global metabolic rates (mean [SD]) in at risk subjects
      (10.5 [1.5] mg per min per 100 g) as compared to affected (9.0 [0.8] mg per min
      per 100 g) and normal control subjects (9.1 [1.5] mg per min per 100 g).
      Normalized (region/global average) regional metabolic rates were reduced in
      cerebellar hemispheres and vermis, and in frontal and prefrontal areas of
      affected subjects in comparison to at risk and normal control subjects. These
      findings indicate that functional changes in some forms of autosomal dominant
      hereditary cerebellar ataxia may extend beyond the cerebellum and brainstem to
      involve other parts of the neuraxis.

PMID- 8277327
TI  - Lack of association between peripheral neuropathy and HTLV-I infection in west
      Africa. Epidemiological, serological and nerve biopsy study.
AB  - Patients (n = 1166) with various neurological disorders hospitalized in Dakar,
      Abidjan, Lome and Ouagadougou were examined prospectively over a 42-month period.
      Seropositivity for HTLV-I alone was found to be 1.8%, which is comparable to that
      estimated for the general population in Africa. Eighteen of the patients with TSP
      and only 5 with PN were HTLV-I positive, but co-infections were found in 30-40%
      of cases. Discrete and unspecific lesions were observed on light and electron
      microscopic examination of peripheral nerve biopsies from 11 patients. Since
      spastic paraparesis emerges as the disorder containing the largest number of HTLV
      I-positive individuals, it may be premature to conclude that HTLV-I is a causal
      agent in PN. Nevertheless, their rarity and the frequency of retroviral co
      infections distinguish these cases of African HTLV-I-associated myelopathy from
      comparable cases observed in other parts of the world.

PMID- 8277328
TI  - Lipocortin 1 (annexin 1) immunoreactivity in the cervical spinal cord of Lewis
      rats with acute experimental allergic encephalomyelitis.
AB  - Spontaneous recovery from acute experimental allergic encephalomyelitis (EAE) by
      the Lewis rat is probably mediated by endogenous corticosteroids. It has been
      proposed that the anti-inflammatory actions of the glucocorticoids may be
      effected via the induction of mediator proteins termed lipocortins and recently
      we have demonstrated increased levels of lipocortin 1 in the central nervous
      system (CNS) of EAE-diseased rats (Bolton C., A-J. Elderfield and R.J. Flower
      (1990), J. Neuroimmunol. 29: 173-181). In this study, utilizing antisera raised
      against recombinant human lipocortin 1, immunohistochemistry and light microscopy
      have been used to determine the distribution of the protein in the cervical
      spinal cord of Lewis rats during EAE. In normal animals lipocortin 1
      immunoreactivity was localized predominantly in the walls of larger blood vessels
      and to a lesser extent capillaries. The same staining pattern was found in
      adjuvant-inoculated controls. In sections from EAE-inoculated animals there was
      no change during the induction phase, but with the onset of clinical symptoms and
      the appearance of inflammatory infiltrates in the CNS, a marked increase in
      lipocortin 1 immunostaining was observed. This additional staining was due to
      widespread immunoreactivity of the lesions, was maximal at the height of disease
      and decreased following recovery and lesion regression. Within the lesions the
      vast majority of infiltrating lymphocytes and macrophages were positive for
      lipocortin 1, including some very heavily stained macrophage-like cells.
      Measurement of corticosterone in the sera of these animals showed that changes in
      lipocortin 1 immunostaining in the CNS during EAE closely parallel serum
      corticosterone levels.

PMID- 8277329
TI  - Impaired induction of vasoactive intestinal polypeptide after sciatic nerve
      injury in the streptozotocin-diabetic rat.
AB  - This study was designed to assess the effects of experimental diabetes and nerve
      crush injury upon vasoactive intestinal polypeptide (VIP) content and axonal
      transport in the dorsal root ganglia (DRG) and sciatic nerve. Sciatic nerve crush
      injury in control and 3-week streptozotocin-diabetic rats was followed 6.5 days
      later by placement of 2 constricting ligatures above the site of injury. After 12
      h, the L4 and L5 DRG and sciatic nerve were removed for VIP radioimmunoassay.
      Similar samples were also taken from control and diabetic rats whose nerve had
      been ligated without a preceding crush. VIP was increased over 2-fold in ganglia
      and 4-fold in nerves of crush-injured controls compared to uninjured controls
      (both P < 0.01). Crush injury also increased ganglion and nerve VIP in diabetic
      rats (P < 0.05 and 0.01, respectively) but the increase was less than what
      occurred in crush-injured controls (both P < 0.05). The accumulation of VIP
      proximal to a sciatic ligature was similar in control and diabetic rats and was
      not altered in either group by crush injury, while retrograde transport of VIP
      was initiated by crush injury in both control and diabetic rats. These data show
      that short-term diabetes does not alter the amount and peripheral axonal
      transport of VIP in the sciatic nerve but impairs the ability of peripheral nerve
      to respond to injury.

PMID- 8277330
TI  - The susceptibility of rat diabetic nerve to ischemia: increased or decreased?
AB  - Diabetic nerve reveals a peculiar paradox between its physiological resistance to
      ischemia, in conducting impulses for longer than control nerve during ischemia,
      and its morphological liability to more severe pathological changes of nerve
      fiber when rendered ischemic. These paradoxical phenomena, however, have never
      been previously evaluated in the same diabetic rat. In the present study, the
      effect of ischemia on rat diabetic nerve was assessed both physiologically and
      morphologically at 2 and 16 weeks after the injection of streptozotocin. At 16
      weeks the effects of a rapid normalization of blood glucose by insulin on these
      phenomena were also evaluated. Two weeks after the induction of diabetes,
      physiological resistance to ischemia was found, but not morphological
      vulnerability. After 16 weeks of diabetes, both physiological resistance and
      morphological vulnerability to ischemia were observed. At this time the
      administration of insulin had no effect on morphological vulnerability, but
      shortened the time of preservation of nerve action potentials during ischemia
      although it was not normalized. These findings indicate that the morphological
      liability of diabetic nerve to ischemia is most likely due to a combined effect
      of systemic complications of chronic hyperglycemia. By contrast a substantial
      component of resistance to ischemic conduction failure appears to be related to
      rapidly reversible metabolic derangement due to hyperglycemia. The study
      demonstrates coexistence of physiological resistance and morphological
      vulnerability to ischemia in rat diabetic nerve, and implies that different
      factors are involved in these paradoxical phenomena.

PMID- 8277331
TI  - Age-related changes in replication of myogenic cells in mdx mice: quantitative
      autoradiographic studies.
AB  - Cell replication in muscle was measured by tritiated thymidine (3H-TdR)
      incorporation and autoradiography, in mdx mice from 2-44 weeks of age. Pre
      mitotic labelling (within 1 h of 3H-TdR injection) was determined in 16 mice aged
      from 15 to 300 days. In 30 further mdx mice, one leg was irradiated 1 h after 3H
      TdR injection to block DNA synthesis. Post-mitotic labelling was measured in both
      legs 10-15 days later. Between 20 and 60 days of age a very high proportion (up
      to 2%) of muscle (satellite cell) nuclei were replicating pre-mitotically; from
      80-300 days cell replication was detectable but at much lower levels. Centrally
      placed nuclei within muscle fibres appeared at 24 days, increased rapidly to 50%
      by 50-100 days, declining thereafter to 25% at 300 days. In post-mitotic samples,
      labelled myotubes and labelled peripheral muscle nuclei (satellite cell nuclei
      and myonuclei) appeared at 28 days and were present in the mdx muscles through to
      310 days, indicating continued cell replication and muscle regeneration. Myogenic
      cell replication was both retarded and inhibited by irradiation. These data
      demonstrate that muscle cell replication in mdx mice commences at about 3 weeks
      of age, is maximal at 4-8 weeks, but continues at lower levels until at least 44
      weeks.

PMID- 8277332
TI  - Unstable DNA in a patient with a severe form of congenital myotonic dystrophy.
AB  - Recently, an unstable DNA (expanded CTG repeat) was identified as the mutation
      that causes myotonic dystrophy (DM). By Southern blot analysis of DNA derived
      from peripheral blood, patients with congenital form of DM are shown to have
      greater expansion of DM specific band than is seen in the analyses of adult form
      of DM. We present here tissue expression of unstable DNA in an autopsied case of
      severe congenital form of DM. Our study revealed the largest expanding band of 19
      kb was uniformly seen in various tissues from an autopsied infant with congenital
      form of DM.

PMID- 8277333
TI  - Antibodies to skeletal muscle in myasthenia gravis. Part 1. Diagnostic value for
      the detection of thymoma.
AB  - The role of anti-muscle antibodies (AMA) in the diagnosis of thymoma in patients
      with myasthenia gravis (MG) is evaluated. We compared ELISA and Western blot
      assay for antibodies to citric acid muscle extract (a-CAE) with an
      immunofluorescence assay (IF). Sera from 234 selected MG patients and 123
      controls were tested. There was no essential difference between ELISA and IF.
      Western blot was superior in young onset patients but less useful in patients
      with an onset beyond the age of 40 years. Unusually high post-test probabilities
      were found by our patient selection criteria which seem most realistic for
      clinical practice. Western blot revealed no differences in specificity of AMA in
      thymoma and non-thymoma patients irrespective of age at onset of disease.

PMID- 8277334
TI  - Inhibition of inflammatory cell-mediated myelin oxidation and interleukin-1 beta
      generation by a 21-aminosteroid, U74500A.
AB  - Inflammatory cell-mediated myelin injury may be an important cause of tissue
      damage in both acute and chronic central nervous system (CNS) disorders. The 21
      aminosteroids are novel derivatives of methylprednisolone without obvious
      glucocorticoid or mineralocorticoid side effects. We evaluated the ability of 21
      aminosteroid, U74500A, to inhibit oxidation of rat brain myelin by human
      polymorphonuclear leukocytes (PMN) and monocytes. Myelin samples, as confirmed by
      SDS-PAGE, were incubated with PMN or monocytes and 100 microM U74500A or vehicle.
      Myelin oxidation by both PMN and monocytes was significantly reduced by U74500A.
      These observations demonstrate that U74500A can inhibit myelin oxidation by
      inflammatory cells. Additionally, 100 microM U74500A significantly reduced
      production of interleukin 1-beta by monocytes exposed to myelin. The
      aminosteroids may be beneficial in CNS disorders where myelin injury by
      inflammatory cells appears to contribute, such as acute focal ischemia or
      multiple sclerosis.

PMID- 8277335
TI  - Selective elimination of macrophages by dichlormethylene diphosphonate-containing
      liposomes suppresses experimental autoimmune neuritis.
AB  - The injection of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP)
      constitutes an effective method to selectively eliminate phagocytic cells from
      spleen, liver and the circulation. We evaluated the effect of Cl2MDP-liposomes on
      the course of actively induced and adoptively transferred experimental autoimmune
      neuritis (EAN), both animal models of the human Guillain-Barre syndrome.
      Injection of Cl2MDP-liposomes 11 and 13 days postimmunization (p.i.) of Lewis
      rats with bovine peripheral nerve myelin efficiently prevented clinical signs of
      EAN up to day 15 p.i., when all control animals were affected. Thereafter, EAN
      gradually also developed in Cl2MDP-liposome-treated rats, but until day 19
      disease was significantly milder than in control rats injected with buffer-filled
      liposomes. Adoptive transfer EAN (AT-EAN) induced by injection of activated P2
      specific T cells could be suppressed even more markedly by application of Cl2MDP
      liposomes 1, 3, and 6 days after cell transfer. Efficient suppression of AT-EAN
      by Cl2MDP-liposomes rules out the possibility that EAN is prevented due to
      interference with the induction phase of this experimental disease and confirms
      that macrophages are important effector cells during EAN. Selective suppression
      of phagocytic cell function by drug-containing liposomes may hold promise as a
      novel treatment of demyelinating autoimmune diseases of the nervous system.

PMID- 8277336
TI  - Alpha B crystallin and HSP28 are enhanced in the cerebral cortex of patients with
      Alzheimer's disease.
AB  - The localization of two small heat shock proteins, alpha B crystallin and 28-kDa
      heat shock protein (HSP28), was studied immunochemically and
      immunohistochemically in cerebral cortex of patients with Alzheimer's disease
      (AD) and control groups. By specific immunoassays for alpha B crystallin and
      HSP28, we found that the concentrations of alpha B crystallin are elevated in the
      temporal and frontal lobes, while those of HSP28 are elevated in the temporal,
      frontal, and parietal lobes in the AD brains. Immunohistochemically, alpha B
      crystallin was localized in astrocytes and oligodendrocytes, while HSP28 was
      present in degenerating neurons in the cerebral cortex of both AD and control
      brains. However, alpha B crystallin-immunoreactive astrocytes and HSP28
      immunoreactive degenerating neurons were more frequently observed in AD brains.
      The immunoreactivity for HSP28 was also found in the senile plaques in the AD
      brains. These findings suggest that the increased accumulations of these small
      heat shock proteins appear to be part of reactive processes of glial cells and
      neurons under pathologic conditions.

PMID- 8277337
TI  - Enhancing the efficacy of thrombolysis by AMPA receptor blockade with NBQX in a
      rat embolic stroke model.
AB  - Efficacy and safety of combined alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionate receptor blockade and thrombolytic therapy with human recombinant
      tissue plasminogen activator (TPA) was tested in a rat embolic stroke model.
      Sixty-three rats were embolized in the right internal carotid territory with a
      200 microliters suspension of microclots formed by alternate moving of 150
      microliters whole blood and 50 microliters of thrombin between two interconnected
      syringes for 4 min. Sixteen embolized rats served as controls, and 16 rats were
      treated with NBQX immediately after embolization. Thirty-one rats were treated
      with TPA 2 h following embolization, and in 16 of these rats additional NBQX
      treatments were initiated 90 min following embolization. Hemispheric cerebral
      blood flow (CBF) was measured by an intraarterial 133Xenon injection method
      before and after embolization. Carotid angiography displayed the rate of
      occlusion of the cerebral arterial supply before and after treatment. Brains were
      fixed after 2 days, evaluated neuropathologically, and infarct volumes were
      measured. Median CBF was reduced by 70-77% in the affected hemispheres following
      embolization. Significant recanalization occurred in all groups except those
      treated with NBQX. TPA-treated rats had significantly better reperfusion compared
      to controls judged by angiography 3 h following embolization (P = 0.04). NBQX
      alone and TPA alone caused insignificant reduction in infarct volume but, when
      combined, total infarct volume was reduced by 77% compared to controls (P =
      0.02). Separate measurement of cortical infarct revealed significantly smaller
      infarcts (P = 0.05) in the combined treatment group compared to the TPA treatment
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277338
TI  - Immunohistochemical patterns of selective cellular vulnerability in human
      cerebral ischemia.
AB  - Although specific patterns of cellular vulnerability have been identified in
      experimental models of cerebral ischemia, there is little data on the occurrence
      of similar abnormalities in human ischemia. We therefore used a variety of
      histochemical methods to define changes affecting specific classes of cells in
      post-mortem specimens from seven patients with hippocampal and neocortical
      ischemic lesions. In acute lesions, staining with SMI-32, an antibody directed
      against nonphosphorylated neurofilaments that labels pyramidal projection
      neurons, was prominently depleted even when conventional Nissl staining revealed
      only mild pyknosis. In contrast, staining for other markers such as microtubule
      associated protein 2 (MAP-2), another cytoskeletal protein, or parvalbumin, a
      calcium-binding protein found in gamma-aminobutyric acid (GABA)-ergic
      interneurons, were relatively preserved. SMI-32 antibody also labeled dystrophic
      axons and axonal retraction balls in and around acute ischemic lesions. The
      pattern of differential changes in immunoreactivity was essentially the same in
      all acute ischemic injuries, including both diffuse lesions in the CA1 field
      (Sommer's sector) and discrete infarcts in CA1 and neocortex. In addition,
      immunoreactivity for the immediate early gene product c-fos was enhanced in and
      around the acute ischemic lesions that we studied. In some very acute lesions,
      immunoreactivity for glial fibrillary acidic protein (GFAP) was depleted in areas
      of severe ischemia and necrosis, but, as expected, GFAP immunoreactivity was
      increased in lesions more than a few days old. In contrast, the loss of SMI-32
      immunoreactivity persisted in chronic lesions. These findings are consistent with
      those of experimental ischemia in animals and confirm the relevance of these
      studies for human cerebral ischemia. The pattern of selective changes also
      resembles that of injuries induced directly by excitatory amino acids, which may
      play a significant role in the pathogenesis of ischemic damage.

PMID- 8277339
TI  - Ultrasonic exploration of the main supra-aortic arteries. B-mode ultrasonography
      continuous wave and pulsed Doppler.

PMID- 8277340
TI  - Colour Doppler imaging of the supra-aortic arterial systems.

PMID- 8277341
TI  - Acute cerebral ischaemia. Exploratory angiography technique.

PMID- 8277342
TI  - Exploratory strategy of cerebral ischaemic accidents before the 6th hour.

PMID- 8277343
TI  - Fibrinolysis in ischaemic vascular cerebral accidents.

PMID- 8277344
TI  - Exploratory strategy 24 hours after established ischaemic accidents in adult.

PMID- 8277345
TI  - Cerebrovascular emergency centres.

PMID- 8277346
TI  - More thinking about critical thinking and clinical decision making.

PMID- 8277347
TI  - The clinical decision-making processes of student nurses.
AB  - This descriptive study examined the clinical decision-making processes used by 19
      female senior diploma nursing students in a simulated client situation. The
      subjects were divided into two groups, with either an internal or external locus
      of control, as measured by the Rotter Internal-External Locus of Control Scale.
      From a content analysis of the data, six decision-making elements and eight
      decision-making processes were identified. The frequency and pattern of use of
      the decision-making processes differed between internally and externally oriented
      subjects. Internal subjects used a significantly higher proportion of complex
      decision-making processes than the external subjects (z = 3.48; p < .01). All
      subjects were found to use decision-making elements and processes in a manner
      that reflected novice characteristics and supported the theoretical framework of
      information-processing theory. These findings have implications for nurse
      educators in relation to teaching strategies that facilitate clinical decision
      making ability and internalization strategies for students with an external locus
      of control.

PMID- 8277348
TI  - The pattern of personal knowing in nurse clinical decision making.
AB  - The struggle to teach clinical decision making effectively continues despite
      recent efforts aimed at improvement. In recognizing that a complex activity like
      clinical decision making entails multiple patterns of knowing, qualitative
      research methodology was used to gain a practice-based understanding of clinical
      decision making. The result is a description of the pattern of personal knowledge
      in nurse clinical decision making. Nurse informants label the pattern of personal
      knowledge as knowing, and describe their success in making clinical decisions as
      highly dependent upon the quality of interpersonal relationships with patients,
      peer nursing staff, and physicians. The dynamic of interpersonal relationships
      and the difficulties in establishing them are identified as important influencing
      factors in nurses' clinical decision making.

PMID- 8277349
TI  - Concept clarification and critical thinking: integrated processes.
AB  - Concept clarification is centrally important to theory development. While often
      understood as a formula-driven task, concept clarification is really a process
      that engages critical thinking. Clarification creates multiple meanings through:
      (1) formulating purposes, (2) choosing, examining, and integrating data sources,
      and (3) representing a final conceptualization that can also be examined for
      adequacy. Within each of these processes, critical thinking is engaged as: (1)
      assumptions are identified and challenged, (2) the importance of context in
      creating meaning is revealed, (3) alternative interpretations are imagined and
      explored, and (4) reflective skepticism is cultivated. The central challenge in
      concept clarification is to understand how words create things.

PMID- 8277350
TI  - Competence validation and cognitive flexibility: a theoretical model grounded in
      nursing education.
AB  - Baccalaureate nursing students' perceptions of learning clinical judgment were
      investigated using grounded theory methodology. Comparative analysis of the
      qualitative data resulted in the development of a preliminary theoretical model,
      competence validation (Loving, 1991), a construct describing the process by which
      the student's identity as a competent nurse is established. The author postulates
      that the outcomes of competence validation vary according to students'
      perceptions of educational context. Two educational contexts, learning and
      evaluation, are described. Students' perceptions of educational context influence
      their motivational orientation which, subsequently, affects students' development
      of cognitive flexibility, the ability to find and apply information that is
      appropriate to patient problem solution. Findings from the study indicate that
      current evaluation practices in nursing education may negatively impact students'
      abilities to learn independent nursing judgment.

PMID- 8277351
TI  - Writing across the curriculum: an integrated curricular approach to developing
      critical thinking through writing.

PMID- 8277352
TI  - Clarifying the concept of critical thinking in nursing.
AB  - Nursing must chart a course between the pedagogical extremes of process versus
      content-focused courses. No one would deny the fact that nurses must have a solid
      knowledge base in addition to demonstrating an ability to think critically.
      Reason favors a "both-and" rather than an "either-or" approach to this issue.
      Justifiably, nurses have jumped on the bandwagon of critical thinking. Once on
      the bandwagon, however, the elusive butterfly of critical thinking has been
      difficult to net. It is time to inform the driver that a new course for nursing
      must be charted. So far, the reported nursing research has focused on critical
      thinking conceptualized as a score on a broad, objective test. The important
      first step of establishing a clear concept that defines critical thinking in
      nursing has not been accomplished. Finding out what the expert nurse does with
      knowledge will help us to articulate a conception of critical thinking that can
      then be used as a springboard for various teaching strategies. If educators are
      persuaded that "students can and should think their way through the content of
      their courses, can and should gain some grasp of the logic of what they study,
      can and should develop explicit intellectual standards, then they can find many
      ways to move instruction in this direction" (Barnes, 1992, p. 22).

PMID- 8277353
TI  - Double immunochemical screening test (hemoglobin and albumin) for the detection
      of occult intestinal bleeding.
AB  - The authors have developed a combined electrophoretic-immunoprecipitation
      technique suitable for the simultaneous demonstration of two blood proteins,
      i.e., hemoglobin and albumin, in the feces. The analytical sensitivity of the
      method is 2 micrograms hemoglobin and albumin/ml. The technique is simple,
      inexpensive, and suitable for the reliable demonstration of occult intestinal
      bleeding for either inpatients or mass screening. This technique is an aid not
      only to the fact that bleeding can be detected, but to its intensity, as well.
      This new technique improves the diagnostic accuracy of early detection of
      carcinomas and polyps, presumably without raising significantly the number of
      "false-positive" reactions.

PMID- 8277354
TI  - Glycoconjugates of Trypanosoma cruzi: a 74 kD antigen of trypomastigotes
      specifically reacts with lytic anti-alpha-galactosyl antibodies from patients
      with chronic Chagas disease.
AB  - Protective, lytic antibodies are believed to be correlated with active
      Trypanosoma cruzi infection. In patients with chronic infection, antibodies
      lysing trypomastigote forms recognize chiefly alpha-galactosyl structures at the
      parasite surface. The target molecules on cell-derived trypomastigotes that react
      with anti-alpha-galactosyl antibodies (anti-Gal) from patients with chronic
      Chagas disease were investigated. Glycoconjugates were isolated from
      trypomastigotes and shown to absorb purified Chagasic (Ch) anti-Gel effectively
      as well as lytic antibodies from Ch sera. Active fractions were F2 (74 kD and
      95.6 kD) and F3 (120-200 kD). A differential reactivity with antibodies from
      untreated Ch patients (trypanolytic) and from treated, presumably cured,
      individuals (not trypanolytic) was evident using F2 and F3 antigenic fractions.
      No cross-reactivity with heterologous sera (other infections) was observed. The
      F2 glycoconjugate (mostly 74 kD) can be used in the diagnosis of active Chagas
      infection, replacing the quantitative determination of complement-mediated lysis.
      With the present sample of patients' sera and normal human sera, it showed 100%
      sensitivity and specificity.

PMID- 8277355
TI  - Chemiluminographic detection of von Willebrand factor multimeric composition.
AB  - Diagnosis of von Willebrand's disease (vWD) requires quantitation of von
      Willebrand factor (vWF) in plasma plus qualitative assessment of the vWF
      multimers according to molecular size ranges. Characterization of vWF multimeric
      size distributions is typically done using sodium dodecyl sulfate-agarose gel
      electrophoresis (SDS-AGE) followed by immunoblotting in the gel with radiolabeled
      antibody against vWF and autoradiographic exposure. We applied a western blot
      technique to vWF multimeric analysis. It included SDS-AGE, electroblotting onto a
      membrane, and chemiluminescent detection using rabbit anti-human vWF as primary
      antibody and goat anti-rabbit IgG as secondary antibody conjugated with
      horseradish peroxidase. Using this method, 18 to 20 vWF multimers were regularly
      resolved in normal plasma with exposure times of 2 to 4 sec compared to 4 hr or
      longer by autoradiography. Sensitivity of detection was at least 4-fold enhanced
      by chemiluminescence compared to radiolabel. Specificity of the assay was
      confirmed by analysis of plasma samples known to be deficient to different
      degrees in the larger vWF multimers. The chemiluminographic assay for vWF
      multimers is superior to the autoradiographic one because it is more sensitive,
      avoids use of radioactivity, and has shorter total assay time (under 2 days
      versus five radiolabel).

PMID- 8277356
TI  - Development of an enzyme immunoassay for the detection of hepatitis B surface
      antigen employing monoclonal antibodies.
AB  - The use of monoclonal antibodies in the development of a third generation
      microtitration plate enzyme immunoassay for the detection of hepatitis B virus
      (HBV) is described. These antibodies were tested either alone or in combination
      with polyclonal antibodies raised in rabbit. Horseradish peroxidase was employed
      in the conjugates and 3,3',5,5'-tetramethylbenzidine was used as the enzyme
      substrate. Effect of type and concentration of antibodies used in the coating
      solution and in preparing conjugates as well as reaction time are discussed. The
      designed test employs a 100-microliters sample, with an overall incubation time
      of 3.5 hr. Serum or plasma (EDTA or citrate as anticoagulant) can be used. The
      sensitivity limit of the test was 0.4 ng/ml for subtype ad and 0.5 ng/ml for
      subtype ay. When used as screening test, 99.6% specificity was obtained;
      predictive value was 97.5% for a positive result and 99.8% for a negative result.
      According to the performance of the test, it seems to be suitable for diagnosis
      in routine laboratory and screening in blood banks.

PMID- 8277357
TI  - Detection of antineutrophil autoantibodies by flow cytometry: use of unfixed
      neutrophils as antigenic targets.
AB  - Antineutrophil antibodies may be found in the sera of patients with chronic
      neutropenia as well as in the sera of a variety of patients with neutropenia and
      associated autoimmune or infectious disorders. We evaluated an immunofluorescent
      flow cytometric technique for the measurement of antineutrophil antibodies in
      serum. Sera from patients with suspected immune neutropenia were studied and
      compared with a group of sera from normal healthy individuals, as well as with
      sera from patients with rheumatoid arthritis and systemic lupus erythematosus. Of
      159 patients with suspected immune neutropenia and a variety of associated
      clinical disorders, 59 (37%) were found to have evidence for enhanced binding of
      IgG to normal target neutrophils, interpreted as positive for antineutrophil
      antibodies. Whereas 0/37 non-neutropenic patients with typical RA had positive
      results, 51/244 (21%) of sera from nonneutropenic patients with SLE or other
      collagen vascular disorders showed enhanced IgG binding to neutrophils. Living
      neutrophils were used to study the effects of cellular activation, and increased
      antibody binding was observed with certain sera that contained IgG directed
      against activation-dependent antigens. We found that, under controlled
      conditions, flow cytometry can be reliably used to detect antineutrophil
      autoantibodies, with unfixed, living neutrophils as antigenic targets.

PMID- 8277358
TI  - Immunoenzymatic assay that measures the expression of murine histocompatibility
      antigens in macrophages and lymphocytes.
AB  - A convenient--simple, sensitive, rapid and reproducible--enzyme immunoassay to
      measure H-2 particulated and solubilized cellular antigens is described. Cellular
      antigens were measured by ELISA through the binding of specific biotinylated
      antibodies and streptoavidin-peroxidase conjugate to cells in suspension.
      Endogenous peroxidase activity of activated cells was inhibited by addition of
      sodium azide and H2O2 in acid conditions. The assay proved capable of
      distinguishing between two cell lines (EL-4/H-2b and P815/H-2d) and even between
      the cells of three congenic mouse strains (BALB/B, H-2b, BALB/c, H-2d, and
      BALB/K, H-2k) and was sensitive to as few as 2.5 x 10(4) cells/well. Results were
      comparable to those obtained with FACS. An inhibition version of this assay was
      found to be very useful for the detection of H-2 antigens present in whole
      antigen cells extracts.

PMID- 8277359
TI  - Enzyme immunoassay and characterization of pancreatic stone proteins in human
      urine.
AB  - An enzyme immunoassay of pancreatic stone protein (PSP) in human urine was
      developed. Mean analytical recovery of pure PSP-S2-5 added to urine was 102.3%
      (SD 5.9%), and the precision of the assay was 2.0-2.7% within an assay and 2.5
      2.9% between assays. In healthy volunteers (age 20-55 years), the mean value of
      the PSP concentration, expressed as ratios to urine creatinine, was 129 +/- 88
      (mean +/- SD) micrograms/g without any differences for sex. Urine PSP correlated
      with urine N-acetylglucosaminidase (NAG) (r = 0.354). The molecular forms of
      immunoreactive PSP in urine were characterized by using cation exchange
      chromatography (Mono S), SDS-PAGE, N-terminal sequence, and enzyme immunoassay
      analysis. The urine PSP, eluted at the position corresponding to PSP-S2-5 on
      cation exchange chromatography, was converted to PSP-S1 by trypsin digestion. The
      difference in mobility on SDS-PAGE between urine PSP and PSP-S2-5 seems to be due
      to a glycosylated undecapeptide (N-terminal 1-11). The proposed method offers a
      sensitive, specific, and reproducible tool for laboratory analysis of human urine
      PSP levels.

PMID- 8277360
TI  - Reticulocyte count with maturation fractions in pancytopenic evaluation by a
      fully automated counter.
AB  - Using a fully automated reticulocyte counter, the roles of the reticulocyte count
      with maturation in pancytopenia were evaluated. Different groups of pancytopenia
      including aplastic anemia, infiltrative marrow disorder, hypersplenism, and
      megaloblastic anemia were recruited. All patients had bone marrow examinations
      for morphological diagnosis and reticulocyte evaluation using an automated
      counter. The roles of these parameters were then analyzed statistically in the
      differential evaluation among these conditions. The following subjects were
      studied: 292 normal subjects, 67 cases of aplastic anemia, 69 cases of marrow
      infiltration by different malignancies, 35 cases of hypersplenism, and 13 cases
      of megaloblastic anemia. The results showed that the absolute reticulocyte counts
      were lowest in the groups of aplastic anemia and megaloblastic anemia and highest
      in hypersplenism. Both showed significant differences from the infiltrative
      groups. The maturation fractions were most immature in the group of marrow
      infiltration and are significantly different from the other groups. It was
      concluded that the highest absolute reticulocyte count (> 0.09 10(12)/L) obtained
      in pancytopenic patients suggests it to be a case of hypersplenism. The lowest
      counts (< 0.03 10(12)/L) with lowest immature fractions (< 10%) suggest the
      groups of aplastic or megaloblastic anemias. The highest immature fractions (>
      30%) with a nearly normal reticulocyte count favor the group of marrow
      infiltration.

PMID- 8277362
TI  - Protein 1: its purification and application in clinical medicine.
AB  - Protein 1 (P1) is a low-molecular-weight protein recently isolated from the urine
      of patients with chronic renal failure. Its molecular weight is 14 kDa on sodium
      dodecyl sulfate polyacrylamide gel electrophoresis and pI 4.7 on isoelectric
      focusing. We purified this protein, characterized its physicochemical properties,
      and analyzed its amino acid sequences to show that it is probably identical to
      human lung Clara cell 10 kDa protein. Its monoclonal antibody was prepared, and a
      reliable enzyme-linked immunosorbent assay employing the sandwich method was
      developed and used to investigate distribution and variation in concentration of
      P1 in various body fluids under an array of physiologic and pathologic
      conditions. Clinical studies indicated that, as is the case with other proteins
      of low molecular weight, the main catabolic site of P1 of plasma origin is the
      kidney: P1 is filtered by the renal glomeruli and reabsorbed by the renal
      tubules. Unabsorbed P1 is thus excreted into the urine. This protein is also
      synthesized in the genital tissues of males, however, from which it is also
      excreted into the urine. Clinical data obtained in our study of this protein is
      summarized here, and an attempt is made to determine the potential value of this
      protein in laboratory medicine.

PMID- 8277361
TI  - Principle and applications of ultrasensitive enzyme immunoassay (immune complex
      transfer enzyme immunoassay) for antibodies in body fluids.
AB  - The sensitivity and specificity of enzyme immunoassay for antibodies in body
      fluids have been improved considerably by transferring the complex of labelled
      antigen and antibody to be detected from one solid phase to another to eliminate
      interfering substance(s) in the samples (immune complex transfer enzyme
      immunoassay). Usefulness of the new method has been tested for antibodies in
      serum as well as in urine. Anti-thyroglobulin IgG could be measured not only in
      serum of all patients with autoimmune thyroid diseases and almost all healthy
      subjects but also in the urine of most of the patients. Anti-HTLV-I IgG was
      unequivocally demonstrated in some of sera, which were indeterminate or negative
      by Western blotting, and diagnosis of HIV infection by detecting anti-HIV IgG in
      urine and saliva would be possible with higher reliability than by conventional
      methods.

PMID- 8277363
TI  - Human thyroid peroxidase: autoantibody recognition depends on the natural
      conformation.
AB  - Thyroid peroxidase (TPO) purified from human thyroid glands was used to study the
      correlation relation between natural conformation and its ability for binding of
      autoantibodies in sera from patients with autoimmune lymphocytic thyroiditis
      (Hashimoto's thyroiditis). Treatment with heat (60 degrees C), urea, sodium
      dodecylsulfate (SDS), and dithiothreitol (DTT) decreased the autoantigenicity of
      TPO on average by 73.3%, 74.1%, 86.3%, and 91.8% measured by enzyme-linked
      immunosorbent assay (ELISA), respectively. These data demonstrate, that the
      binding of the majority of autoantibodies to human TPO depends on its natural
      conformation and modification.

PMID- 8277364
TI  - Bone biopsy in renal osteodystrophy.

PMID- 8277365
TI  - Arrhythmogenic right ventricular cardiomyopathy.

PMID- 8277366
TI  - Identification of numerical chromosome aberrations in archival tumours by in situ
      hybridization to routine paraffin sections: evaluation of 23 phaeochromocytomas.
AB  - We have applied non-isotopic in situ hybridization (ISH) to interphase cell
      nuclei of 23 phaeochromocytomas (18 primary and 5 metastatic tumours) within
      routine paraffin-embedded tissue sections. Each tumour was screened for numerical
      aberrations with a defined alphoid repetitive DNA probe set containing DNA probes
      specific for chromosomes 1, 7, 15, and Y. Normal adrenal medullas and other
      normal human cell types served as cytogenetic controls. Preservation of tissue
      morphology enabled targeted analysis of tumour cells. The presence of numerical
      chromosome changes in the tumour cells could easily be evaluated by comparing the
      ISH results of the DNA probes. Numerical abnormalities not previously reported in
      this neoplasm included overrepresentation of chromosomes 1 and 7, loss of
      chromosome 15, and both gain and loss of chromosome Y (P values < 0.01). The
      percentage of aneuploid cell nuclei in a tumour correlated well with the
      percentage of cells in the 4C peak of flow cytometric DNA histograms from these
      neoplasms. We conclude that interphase ISH can be used for the identification of
      new and reported cytogenetic changes in tumour cell nuclei within archival tissue
      sections. This novel procedure also allows for retrospective analysis of
      previously not karyotyped material.

PMID- 8277367
TI  - Loss of alpha 6 and beta 4 integrin subunits coincides with loss of basement
      membrane components in oral squamous cell carcinomas.
AB  - In oral squamous cell carcinomas, focal or extensive loss of basement membrane
      components and of integrins has been reported. The purpose of this study was to
      investigate whether those regions of the tumour-connective tissue interface which
      lack laminin and type IV collagen coincide with areas of loss of the alpha 6 and
      beta 4 integrin subunits on basal keratinocytes. Out of a total of 15 poor and
      moderately or well differentiated squamous cell carcinomas, all showed some loss
      or fragmentation of basement membrane proteins and in 12 the loss was coincident
      with loss of alpha 6 and/or beta 4. In three cases, there was loss of basal
      integrin expression in areas where the basement membrane remained intact. These
      results provide further evidence that loss of integrins may play an important
      role in tumour progression and prompt us to speculate about the sequence of
      events leading to tumour invasion.

PMID- 8277368
TI  - TGF-beta s and TGF-beta type II receptor in human epidermis: differential
      expression in acute and chronic skin wounds.
AB  - Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance
      wound healing processes in animal models; however, little is known about the
      expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin
      or during wound healing. The present study has revealed several unexpected
      findings by means of in situ hybridization and immunohistology techniques. In
      humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin
      and in that of acute and chronic wounds--a pattern of expression closely mirrored
      by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta
      1 mRNA expression was observed in the regenerating epidermis of acute (thermal)
      wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA
      expression was not detected in the epidermis of any human skin or wound biopsies.
      From these findings we suggest that constitutive expression of TGF-beta 3 is
      important for maintenance of epidermal differentiation and that an induction of
      TGF-beta 1 expression is essential for re-epithelialization of human skin wounds.
      Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with
      their protracted healing tendencies.

PMID- 8277369
TI  - Proliferative activity as revealed by Ki-67 in uterine adenocarcinoma of
      endometrioid type: comparison of tumours from patients with and without previous
      oestrogen therapy.
AB  - The Ki-67 antibody recognizes a nuclear antigen related to cell proliferation,
      which in some studies has been shown to reflect the aggressiveness of tumours.
      The percentage of Ki-67-positive cells was estimated by immunohistochemistry on
      frozen tissue sections from 73 adenocarcinomas of endometrioid type (EC) (40
      tumours from patients who had never received postmenopausal oestrogen treatment
      and 33 tumours from patients with previous postmenopausal oestrogen treatment).
      The Ki-67 content was weakly but significantly (P < 0.05) correlated to nuclear
      grade, architectural grade, and crude mitotic count, but not to stage or
      progesterone receptors. Ki-67 expression in EC from patients with previous
      oestrogen therapy was much lower (median 10 per cent Ki-67) than that in EC from
      patients who had never received oestrogen treatment (median 24 per cent Ki-67),
      suggesting that a prognostic cut-off point may be different in tumours from the
      two groups of patients. The mitotic count discriminated the two groups of
      patients to a much smaller degree. It is also shown that a quick qualitative Ki
      67 estimate can replace the time-consuming quantitative assessment.

PMID- 8277370
TI  - Parathyroid hormone-related protein (PTHrP) gene expression in solid tumours
      associated with normocalcaemia and hypercalcaemia.
AB  - Parathyroid hormone-related protein (PTHrP) is an important humoral factor in the
      syndrome of humoral hypercalcaemia of malignancy (HHM) and its importance is
      evident by the many studies examining either PTHrP mRNA expression, intracellular
      peptide, or circulating PTHrP levels in patients with malignancy. However, the
      relationship between PTHrP mRNA expression, intracellular localization of
      peptide, and circulating PTHrP levels in the same group of patients with
      malignancy has not been examined. This study was carried out to explore this
      relationship in a group of patients with solid tumours associated with either
      normocalcaemia or hypercalcaemia. PTHrP mRNA and peptide were localized by in
      situ hybridization and immunohistochemistry respectively in 26 squamous
      carcinomas and 15 adenocarcinomas from patients who were either hypercalcaemic or
      normocalcaemic. Plasma PTHrP1-86 and serum PTH1-84 concentrations were measured
      by two-site immunoradiometric assays. PTHrP mRNA and peptide were localized in 11
      (100 per cent) and 10 (91 per cent) of 11 squamous tumours from hypercalcaemic
      patients, all of whom had detectable circulating PTHrP levels, and in 14 (97 per
      cent) and 11 (73 per cent) respectively of 15 squamous tumours from
      normocalcaemic patients. PTHrP mRNA and peptide were localized in only two (28
      per cent) and four (57 per cent) respectively of seven adenocarcinomas associated
      with hypercalcaemia. Since the majority of squamous tumours synthesized PTHrP
      irrespective of the calcium status of the patient, this suggests that the
      clinical expression of tumour-derived PTH-like bioactivity may depend on the rate
      of secretion of PTHrP rather than gene expression, and that the bioactivity of
      secreted PTHrP may be modulated by post-translational processing.

PMID- 8277371
TI  - Thymic extracellular matrix in human malnutrition.
AB  - Previous studies have shown that malnutrition severely affects both lymphoid and
      epithelial components of the thymus. Yet, few data are available concerning the
      extracellular matrix (ECM) of the thymic microenvironment in malnutrition. We
      studied by histological, ultrastructural, and immunohistochemical means thymuses
      obtained in necropsies from 19 malnourished children. We observed a consistent
      increase in the intralobular ECM-containing network which could be ascertained
      histologically by the dense reticulin staining. This abnormally dense ECM network
      contained fibronectin, laminin, and type IV collagen. Importantly, the
      enhancement of thymic ECM in malnourished individuals positively correlated with
      the degree of thymocyte depletion. This correlation may represent a cause-effect
      relationship in which the contact of thymocytes with abnormally high amounts of
      thymic ECM triggers and/or enhances programmed cell death.

PMID- 8277372
TI  - Tissue iron loading and histopathological changes in hypotransferrinaemic mice.
AB  - Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a
      model for genetic (primary) haemochromatosis. Iron loading of liver preceded that
      in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in
      exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth
      muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets
      of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas
      was fibrotic with massive macrophage infiltration and loss of secretory
      epithelium. Liver showed evidence of chronic inflammatory infiltration with
      increased collagen fibres in the parenchymal region but no cirrhosis. Serum
      aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx
      compared with wild-type mice. Heavy iron loading with haemosiderin deposition in
      the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous
      hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12
      weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were
      also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice
      showed evidence of liver and pancreatic damage secondary to tissue iron overload.
      The iron loading pattern and tissue damage showed some features which were
      distinct from those observed in haemochromatosis.

PMID- 8277373
TI  - Characterization of the N-linked oligosaccharides in glycoproteins synthesized by
      microfilariae of Dirofilaria immitis.
AB  - In this report, we describe studies on the structures of the N-linked
      oligosaccharides contained in glycoproteins synthesized by microfilariae of the
      canine heartworm, Dirofilaria immitis. Microfilariae were incubated in media
      containing either 2-[3H]mannose, 6-[3H]glucosamine, or 6-[3H]galactose. Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis and fluorographic analyses
      indicated that many glycoproteins were radiolabeled by both the mannose and
      glucosamine, whereas glycoproteins were not radiolabeled by the galactose.
      Glycopeptides from these total glycoproteins were fractionated and purified by
      serial lectin affinity chromatography, and the structures of the oligosaccharides
      in the isolated glycopeptides were analyzed by a variety of techniques. The N
      linked oligosaccharides were shown to contain mannose (Man), fucose, N
      acetylglucosamine (GlcNAc), and N-acetylgalactosamine (GalNAc). However, they
      lacked sialic acid and galactose, which are commonly found in mammalian
      glycoproteins. GalNAc was shown to be in an unusual terminal position and beta
      linked in the sequence GalNAc beta GlcNAc beta Man-R, where R is the typical
      branch of complex-type N-linked oligosaccharides. Similar structures were
      recently found by us to be synthesized by the helminthic parasite Schistosoma
      mansoni. These results demonstrate that glycoproteins synthesized by
      microfilariae of D. immitis have unusual carbohydrate moieties and may lead to a
      better understanding of the specific roles of glycoprotein oligosaccharides in
      host-parasite interactions.

PMID- 8277374
TI  - Proteolytic cleavage of bovine IgG by hypodermin A, a serine protease of
      Hypoderma lineatum (Diptera: Oestridae).
AB  - Cattle grub larvae are able to survive a lengthy 8 1/2-mo internal migration
      within the naive bovine host connective tissues. Larval survival is observed even
      in the presence of host immunological responses to principal parasite proteins.
      In this study, data are presented that suggest that a digestive enzyme,
      hypodermin A, of the first-instar larvae effectively cleaves bovine
      immunoglobulin G in vitro. A (fab)'2 fragment is produced, and the heavy-chain
      fragments associated with the cleaved fc piece remain intact. Hypodermin A is not
      specific for bovine IgG as other species' IgGs are also degraded as are other
      bovine proteins. Destruction of the biological activity of bovine immunoglobulin
      G by hypodermin A suggests a potential parasite escape mechanism that may
      contribute to the survival of first-instar larvae within the bovine host.

PMID- 8277376
TI  - Ctenascarophis lesteri n. sp. and Prospinitectus exiguus n. sp. (Nematoda:
      Cystidicolidae) from the skipjack tuna, Katsuwonus pelamis.
AB  - Two cystidicolid nematodes, Ctenascarophis lesteri n. sp. and Prospinitectus
      exiguus n. sp., are described from the skipjack tuna, Katsuwonus pelamis, from
      Fiji, New Caledonia, Marquesas Islands, New Zealand, Papua New Guinea, and Puerto
      Rico. The former species differs from Ctenascarophis gastricus, the only other
      member of the genus, by having comb rows extending farther posterior than two
      thirds the body length, to the anus in the female; it also has differently
      distributed spines on each comb, with a maximum of 32 rather than 8. The male has
      7 rows of precloacal longitudinal crests; 3 pairs of precloacal, 1 pair adanal,
      and 6 pairs postcloacal papillae; and a spicule ratio of 1:3.4-1:5.0. The latter
      species differs from Prospinitectus mollis, the only other species in the genus,
      by being less than one-half as long, 3.5-5.9 mm long; with a proportionally
      longer esophagus; fewer spines per spine ring, a maximum of 49 compared with 100;
      deirids that lack spinules; males with an unornamented precloacal cuticle as well
      as a different number and distribution of caudal papillae, 2 precloacal and 7
      postcloacal; and a smaller spicule ratio, 1:4 rather than 1:5-1:7.

PMID- 8277375
TI  - Changes in lipids of the salivary glands of the lone star tick, Amblyomma
      americanum, during feeding.
AB  - The lipid composition of salivary glands from male and female lone star ticks,
      Amblyomma americanum, was investigated at progressive stages of tick feeding. The
      amounts of fatty acids from both phospholipid and neutral lipid fractions
      increased dramatically during the initial stage of feeding and peaked in
      partially fed females weighing 100-250 mg. Percentage compositions of myristic
      (14:0) and palmitic acid (16:0) decreased, but stearic (18:0), oleic (18:1),
      linoleic (18:2), and arachidonic acid (20:4) increased during tick feeding.
      Arachidonic acid, the precursor to eicosanoids including the 2-series of
      prostaglandins, increased from 1.3% of all fatty acids in salivary glands from
      unfed female ticks to 8.2% in salivary glands from fully engorged female ticks.
      Arachidonic acid was found in the triglyceride fraction of unfed and fed virgin
      females but only in phosphatidylcholine and phosphatidylethanolamine from
      salivary glands of other fed female ticks. Comparisons between fed and unfed male
      ticks and fed/virgin, fed/mated, and unfed females demonstrate that feeding is
      necessary for accumulation of arachidonic acid in salivary gland phospholipids.

PMID- 8277377
TI  - First description of the male and redescription of the immature stages of
      Amblyomma rotundatum (Acari: Ixodidae), a recently discovered tick in the U.S.A.
AB  - The male of Amblyomma rotundatum is described for the first time, and the nymph
      and larva are redescribed. This tick is a parthenogenetically reproducing species
      parasitic on amphibians and reptiles in the warmer areas of the New World.
      Attempts to mate male and female A. rotundatum under laboratory conditions were
      unsuccessful.

PMID- 8277378
TI  - Prevalence of eyeworms (Nematoda: Thelazioidea) in beef cattle grazing different
      range pasture zones in Alberta, Canada.
AB  - The eyes from 410 beef cattle grazing 6 range pasture zones in Alberta were
      dissected and examined for species of Thelazia. Thirty-eight (9.3%) contained
      eyeworms: 25 (6.1%) contained Thelazia skrjabini alone, 3 (0.7%) contained
      Thelazia gulosa alone, and 10 (2.4%) had a mixed infection of T. skrjabini and T.
      gulosa. Prevalence was related to the type of pasture. The prevalence was lower
      in cattle grazing short- and mid-grass pastures (zones 1, 2; 0% and 1.5%,
      respectively) than those grazing transitional or aspen parkland pastures (zones
      3, 5; 7.4% and 6.2%, respectively) or rough fescue or woodland type pastures
      (zones 4, 6; 11.3% and 18.4%, respectively). The data suggest that prevalence is
      related to pasture type that limits the number of its vector, Musca autumnalis.

PMID- 8277379
TI  - Prevalence of encysted Toxoplasma gondii in raptors from Alabama.
AB  - Little is known about the prevalence of encysted Toxoplasma gondii in wild birds.
      We examined the hearts and breast muscles from 101 raptors for encysted T.
      gondii. All of the raptors had been submitted for necropsy to the State
      Veterinary Diagnostic Laboratory, Auburn, Alabama. Tissues were digested in acid
      pepsin solution and inoculated into groups of 3-5 laboratory mice. Toxoplasma
      gondii was isolated from 27 of 101 (26.7%) raptors: 8 of 12 (66.7%) red
      shouldered hawks (Buteo lineatus), 13 of 27 (41.1%) red-tailed hawks (Buteo
      jamaicensis), 1 of 4 (25%) Cooper's hawks (Accipiter cooperi), 1 of 5 (20%) great
      horned owls (Bubo virginianus), 4 of 15 (26.7%) barred owls (Strix varia), and 1
      of 3 (33.3%) kestrels (Falco sparverius). Toxoplasma gondii was not isolated from
      3 broad-winged hawks (Buteo platypterus), 3 sharp-shinned hawks (Accipiter
      striatus), 6 barn owls (Tyto alba), 9 screech owls (Asio otus), a Mississippi
      kite (Ictinia misisippiensis), 2 golden eagles (Aquila chrysaetos), a bald eagle
      (Haliaeetus leucocephalus), 4 ospreys (Pandion haliaetus), 4 turkey vultures
      (Cathartes aura), or 2 black vultures (Coragyps atratus). No significant
      difference (P > 0.05) in prevalence was detected based on sex using chi-square
      analysis. Chi-square analysis of the data demonstrated that adult raptors had
      encysted stages of T. gondii significantly (P < 0.05) more often than did
      immature raptors.

PMID- 8277380
TI  - Description of Ostertagia ostertagi and Ostertagia leptospicularis hybrids in
      experimentally infected sheep.
AB  - Hybrids of Ostertagia ostertagi and Ostertagia leptospicularis, derived from
      experimental infections in sheep, are described. Morphometrics of the hybrids
      were intermediate between those of parental lines for a large range of parameters
      (distance from apex to cervical papillae and length of esophagus for males and
      females, length of spicules for males, and length of vestibule, distance from
      vulva to the end of tail, width of tail at anus). The morphological relationship
      between hybrids and their parent species was assessed by discriminant analysis
      based on the relative values of these parameters (actual value/length of the
      worm). Each parental line, either bred in sheep or in the natural host, was
      morphologically similar and differed from hybrids.

PMID- 8277381
TI  - ELISA method for detecting anti-Plasmodium relictum and anti-Plasmodium elongatum
      antibody in infected duckling sera using Plasmodium falciparum antigens.
AB  - An enzyme-linked immunosorbent assay (ELISA) with 3 Plasmodium falciparum NF-54
      antigens, R32tet32, P.F.R27, and crude red blood cell extract (CRBCE), was tested
      for detection of anti-Plasmodium relictum and anti-Plasmodium elongatum
      antibodies in sera from experimentally infected ducklings. Whole blood, serum,
      and dried blood on filter paper gave similar results. The latter was selected for
      convenience. All birds infected by experimental blood challenge, but not exposed
      to sporozoites, had detectable antibody (up to 1.0 x 10(-3.8) dilution) reactive
      with R32tet32, P.F.R27, and CRBCE antigens. Ducklings infected with P. elongatum
      had higher antibody levels than those infected with P. relictum. In a blind
      trial, the described ELISA accurately distinguished sera taken from infected and
      uninfected ducklings. This study provides the first evidence on cross reactivity
      in the ELISA format between P. falciparum antigens and antibodies induced by P.
      relictum and P. elongatum in experimentally infected ducklings. The proposed
      ELISA is fast, easy to perform, reproducible, and requires a minimal amount of
      equipment. The assay can be used for the detection of P. relictum and P.
      elongatum antibodies in captive or wild ducks, along with monitoring the level of
      antibody in selected groups of birds or for surveys of laboratory experiments
      where evidence of infection is required.

PMID- 8277382
TI  - The parasite assemblage in the spiral intestine of the shark Mustelus canis.
AB  - The parasite assemblage in the 8 chambers of the spiral intestine of 49 specimens
      of the shark Mustelus canis collected from Long Island Sound and off the coast of
      Virginia was investigated. Assemblages within host individuals were composed of
      up to 3 of 4 species of cestodes: the trypanorhynch species Prochristianella
      tumidula and Lacistorhynchus tenuis and the hooked tetraphyllidean species
      Calliobothrium verticillatum and Calliobothrium lintoni. Each individual shark
      hosted 1-3 (mean = 2.17) tapeworm species and 1-166 (mean = 34.3) tapeworm
      individuals. The assemblage consisted of 2 core species, 1 secondary species, and
      1 satellite species. Analysis of variance (ANOVA) revealed significant
      differences among the areas of the 8 intestinal chambers. ANOVAs of worm density
      among chambers revealed that each of the 4 species exhibited site specificity
      within the spiral intestine. Least significant difference analysis revealed that
      each of the species, except C. verticillatum, was usually found in the anterior 3
      chambers. Calliobothrium verticillatum was more commonly found in the middle
      region of the organ, centered around chamber 4. Horn's information index
      indicated that L. tenuis and C. lintoni had the greatest amount of overlap within
      the spiral intestine and the congeners C. lintoni and C. verticillatum had the
      least amount of overlap. No evidence of interaction among the species in this
      assemblage was found. In cases where observations could be made, neither cestode
      total length nor location within the spiral intestine appeared to be affected by
      the presence of other individuals or species respectively. There was some
      evidence of underutilized space; the posteriormost chamber was vacant in all 49
      sharks examined and 91.8% of sharks had at least 2 vacant chambers. Linear
      regression revealed no relationship between shark total length and either total
      number of worms or total number of individuals of each of the 4 species of
      cestodes. The chi-square test revealed no evidence that the 4 species do not
      occur independently among host individuals. The number of species and number of
      individuals in M. canis were low when compared to the marine fish Sebastes
      nebulosus. These values for M. canis more closely resemble values for freshwater
      fishes. The comparatively much greater host specificity of these tapeworms may at
      least partially account for this difference. We propose that site specificity may
      have a phylogenetic component, in a manner similar to that of host specificity.

PMID- 8277383
TI  - Localization of a low abundance membrane protein (Bm86) on the gut cells of the
      cattle tick Boophilus microplus by immunogold labeling.
AB  - A preembedding immunogold technique was used to locate Bm86, an antigen from the
      gut digest cells of the cattle tick Boophilus microplus. Gut from partially
      engorged female ticks was everted to expose the cells, lightly fixed in 4%
      paraformaldehyde, and then incubated in rabbit antisera against a recombinant
      form of Bm86. Following incubation in a secondary antibody conjugated to 1-nm
      colloidal gold, Bm86 antigenic sites were visualized for both light and electron
      microscopy using silver enhancement. Bm86 was shown to be located predominantly
      on the microvilli of digest cells. Antiserum against a nonglycosylated
      Escherichia coli recombinant form of Bm86 was used to avoid cross-reactivity with
      carbohydrate epitopes of other digest cell proteins.

PMID- 8277384
TI  - Acquired resistance of guinea pigs to Dermacentor andersoni mediated by humoral
      factors.
AB  - Humoral and cell-mediated immune resistance to tick infestation has been
      documented in many host-parasite relationships. This study examines passive
      transfer of resistance to Dermacentor andersoni expressed by recipients of serum
      pools derived from guinea pigs that had acquired resistance through experimental
      infestation. Recipients of sera from high titer adult-infested animals expressed
      resistance evidenced by reduced engorgement weights, histological changes at tick
      attachment sites, and tick antigen-reactive cytophilic antibody. Recipients of
      lower titer sera from nymph-infested guinea pigs did not show significant
      reductions in engorgement weights but did exhibit inflammatory reactions at tick
      attachment sites similar to those of high titer sera recipients. This study,
      together with previous findings, suggests that immature instars of D. andersoni
      may not be as effective as adult ticks in stimulating sufficient humoral
      responses to convey biological resistance to naive recipients, and it underscores
      the influence the route of serum administration can have on passive transfer
      studies.

PMID- 8277385
TI  - Culture of cells from juvenile worms of Schistosoma mansoni.
AB  - Tissue disruption methods were developed and serum-free cell culture media
      formulated for the maintenance in vitro of cells from juvenile worms (day 18
      after infection) of Schistosoma mansoni. Cultures maintained viability for up to
      6 mo when plated on a feeder layer of irradiated rat liver cells and survived
      primarily as clusters of small (2.5-4 microns diameter) cells with a high nuclear
      to-cytoplasmic ratio and relatively few organelles identified by electron
      microscopy. Cultures synthesized a protein profile similar to that of intact
      worms, and the cell clusters maintained a time- and concentration-dependent
      contractile response to serotonin. Cells synthesizing DNA were detected by
      precursor incorporation and flow cytometry in cultures initially and also after
      several weeks in vitro, although the percentage of cells synthesizing DNA
      decreased with time. Efforts to identify peptide growth factor-responsive
      tyrosine phosphorylation were negative, and the overall amount of S. mansoni
      phosphotyrosine-containing proteins identified by western blot with anti
      phosphotyrosine monoclonal antibody was much less than that found in a peptide
      growth factor-responsive mouse cell line.

PMID- 8277386
TI  - Effects of source of metacercariae on experimental infection of Zygocotyle lunata
      (Digenea: Paramphistomidae) in CD-1 mice.
AB  - Outbred (CD-1 strain) mice were infected experimentally with metacercariae of
      Zygocotyle lunata obtained from naturally infected Helisoma trivolvis. Growth,
      survival, and fecundity of the parasite and gross pathology in the host were
      evaluated. Metacercariae from 5 snail sources produced 3 patterns of growth and
      survival: significantly smaller worms that survived less than 4 wk and did not
      mature, significantly larger worms that matured but survived less than 6 wk, and
      worms of intermediate size that matured and lived at least 19 wk. Parasite
      maturation (at 3-4 wk) and egg production (14 eggs.worm-1.hr-1) were similar
      among infections from different sources. Ceca of mice with infections at least 4
      wk old were enlarged with localized mucosal alteration at the site of parasite
      attachment, but there was no evidence of splenomegaly. The differences in
      infection due to the source of metacercariae within 1 strain of final host were
      similar to differences reported among other species of final host. These results
      suggest that variation associated with the intermediate host may confound studies
      of specificity to the definitive host.

PMID- 8277387
TI  - Experimental toxoplasmosis in bobwhite quail (Colinus virginianus).
AB  - Twenty-four 3-5-mo-old battery-hatched bobwhite quail were inoculated orally with
      10(5) (ME 49 strain, group A, 6 birds), 10(4) (ME 49 strain, group B, 6 birds),
      10(5) (GT-1 strain, group C, 6 birds), and 10(4) (GT-1 strain, group D, 6 birds)
      Toxoplasma gondii oocysts. One quail in group B died 18 days after inoculation
      (DAI) due to undetermined etiology. Two quail from group C and 1 quail from group
      D given GT-1 oocysts died of acute toxoplasmosis 6, 7, and 8 DAI, respectively;
      numerous T. gondii tachyzoites were found in lesions in visceral tissues. The
      surviving quail in group A and B were killed 106 DAI and those in groups C and D
      were killed 60 DAI. Toxoplasma gondii was isolated from pooled tissues of 4 of 5
      quail in group B. Brains, hearts, and skeletal muscles from quail in groups A, C,
      and D were bioassayed individually in mice; T. gondii was isolated from the
      brains of all 6, hearts of 3, and skeletal muscles of 2 of the 6 quail in group
      A; from the brains of all 4, hearts of 1, and skeletal muscles of 2 of the 4
      quail in group C; and from the brains of all 5, hearts of 1, and skeletal muscles
      of 3 of the 5 quail in group D. Toxoplasma gondii antibodies were found in sera
      of all 20 quail killed 60 or 106 DAI. Antibody titers detected in the modified
      agglutination test using whole tachyzoites were higher than in latex
      agglutination and indirect hemagglutination tests that used soluble antigens.
      Antibodies were not detected in a 1:4 dilution of 19 of 20 quail sera in the
      Sabin-Feldman dye test.

PMID- 8277388
TI  - Globule leukocytes in the lumen of the small intestine and the resistance status
      of sheep infected with parasitic nematodes.
AB  - The presence of globule leukocytes in the lumen (LuGLs) of the small intestine
      was studied in Romney sheep reared parasite free and then experimentally infected
      or immunized with Trichostrongylus colubriformis infective larvae, or naturally
      infected when gazed on pasture. It was discovered that high numbers of LuGLs were
      associated with both parasitic infection and the sheep protective immune
      response. A high positive correlation was observed between LuGLs and tissue
      globule leukocytes. The highest correlation (r = 0.92) observed was between
      larval migration inhibition (LMI) and numbers of LuGLs. This was the only
      correlation between LMI and other parameters studied. Significant positive
      correlations were also observed between LuGLs and IgG1 and eosinophils. There was
      a negative correlation between LuGLs and the number of parasites in the intestine
      and parasite egg production. Progeny of genetically resistant and susceptible
      sires had significantly different abilities to produce LuGLs.

PMID- 8277389
TI  - Experimental toxoplasmosis in turkeys.
AB  - Fourteen 2-3-wk-old turkeys were inoculated orally with 10(5) or 10(4) infective
      oocysts of the ME 49 strain of Toxoplasma gondii. Of the 8 turkeys given 10(5)
      oocysts in experiment 1, 3 died or were killed 12 or 14 days after inoculation
      (DAI) because of respiratory distress associated with a concomitant Aspergillus
      like fungus infection. The remaining 5 turkeys remained normal and were killed 62
      DAI. Toxoplasma gondii was isolated in mice from the heart of all 5, from the
      breast muscles of 2, leg muscles of 3, and from the brains and livers of none of
      the turkeys. All 6 turkeys fed 10(4) oocysts in experiment 2 remained clinically
      normal until necropsy on 41 DAI; T. gondii was isolated from pooled tissues from
      each turkey. All 14 turkeys developed high antibody titers to T. gondii in the
      modified agglutination test (MAT) using formalinized tachyzoites. The enzyme
      linked immunosorbent assay (ELISA) was as sensitive as MAT for detecting T.
      gondii antibodies in turkey sera. The latex agglutination and indirect
      hemagglutination tests were less sensitive than the MAT and ELISA. No dye-test
      measurable antibodies were found in sera of any turkey.

PMID- 8277390
TI  - Centrorhynchus aluconis (Acanthocephala) and other helminth species in tawny owls
      (Strix aluco) in Great Britain.
AB  - Observations on the distribution of Centrorhynchus aluconis (Acanthocephala) and
      6 other species of helminths in the definitive host Strix aluco, in tawny owl,
      are presented. Infected owls were collected from 16 sites ranging from Tarbet,
      Strathclyde, Scotland, to Ewhurst, Surrey, in the south of England. In addition,
      unidentified cyclophyllidean cestodes were found in the alimentary tract of the
      tawny owls. Centrorhynchus aluconis was the most prevalent helminth found and had
      the highest intensity. It appears that C. aluconis is widely distributed in the
      tawny owls of Great Britain. Porrocaecum spirale (Nematoda) was the second most
      prevalent species of helminth. This species and C. aluconis are believed to be
      dependent on shrews (Sorex araneus and Sorex minutus) for their transmission to
      owls.

PMID- 8277391
TI  - Effect of a single Lernaeocera branchialis (Copepoda) on growth of Atlantic cod.
AB  - A study was conducted to determine the influence of controlled water temperature
      on growth rate of Atlantic cod (Gadus morhua) after infection with a single,
      blood-feeding copepod, Lernaeocera branchialis. Initially, uninfected and
      infected fish were held in ambient seawater (0-10 C) in a raceway and fed to
      satiation from October to March. In a second trial simulating the water
      temperature at which cod live in winter (2-3 C), 2 groups of fish were kept in
      tanks through which sea water flowed, and they were fed to satiation from
      February through July. Infected cod held at the ambient temperature consumed more
      feed, had comparable weight-gain, and showed lower feed conversion efficiency (%)
      and k-factor than did control fish during autumn to early winter, whereas no
      difference was apparent during the remaining winter period. Also, no striking
      difference in feed consumed, weight gained, feed conversion efficiency or k
      factor were apparent when the 2 groups of cod were held in heated sea water
      during winter to early summer. These results suggest that adult cod infected with
      1 L. branchialis compensate for the infection in autumn rather than during winter
      by consuming more fed.

PMID- 8277392
TI  - Larval nematodes infecting Amphiporeia virginiana (Amphipoda: Pontoporeioidea) on
      Sable Island, Nova Scotia.
AB  - Three species of larval nematodes were found infecting the nearshore subtidal
      amphipod Amphiporeia virginiana collected from beaches on Sable Island, Nova
      Scotia. Five and 2 sealworms, Pseudoterranova decipiens s.l., were found in 2,020
      and 2,044 amphipods, respectively, collected in 1991 and 1992, dissected, and
      examined microscopically. Two sealworms, 1 Paracuaria adunca and 1 Ascarophis
      sp., were found in 5,157 amphipods collected in 1992 and enzymatically digested.
      Infection with each species constitutes a new host record. These 3 nematodes
      possess the capability to infect a wide variety of invertebrate intermediate
      hosts. The shoreline niche of A. virginiana places it in close proximity to the
      sealworm's definitive host, the grey seal, which hauls out on Sable Island in
      abundance. The amphipod's distribution also places it in the vicinity of both the
      definitive hosts of Ascarophis sp. (marine fish) and P. adunca (piscivorous
      birds).

PMID- 8277393
TI  - Absence of typical Nippostrongylus brasiliensis self-cure in putative BALB/c
      mice.
AB  - Rejection of Nippostrongylus brasiliensis in mice typically occurs by 14 days
      postinfection (PI). We report here on a putative BALB/c mouse strain from the
      University of Texas at El Paso (UTEP) animal colony that did not exhibit a normal
      pattern of self-cure. Following subcutaneous inoculation with approximately 500
      third-stage larvae of N. brasiliensis, the parasite was present in substantial
      numbers in UTEP BALB/c mice on days 21 and 28 PI and in low numbers through day
      70 PI regardless of host sex. Normal self-cure was observed using identical
      techniques in 2 other BALB/c strains and a CFW strain. Hence, the UTEP BALB/c
      mouse provides a unique tool to examine the immune response to N. brasiliensis.

PMID- 8277394
TI  - Rapid miniprep isolation of mitochondrial DNA from metacestodes, and free-living
      and parasitic nematodes.
AB  - A method, based on one to isolate supercoiled plasmid DNA from bacterial cells,
      has been developed to purify mitochondrial DNA (mtDNA) from cestode and nematode
      tissue easily and efficiently. Starting with as little as 100 mg of helminth
      tissue, sufficient mtDNA for electrophoretic analysis was extracted. This DNA was
      essentially free of nuclear DNA and readily digested by restriction
      endonucleases. Approximately 20% of the mtDNA in helminth tissue was recovered,
      which is a significant improvement over previously available techniques.

PMID- 8277395
TI  - An experimental test of the site specificity of preening to control lice in feral
      pigeons.
AB  - Site specificities of ectoparasites on the host may have evolved due to the
      selective pressure exerted by host grooming. The present study demonstrates that
      the efficiency of avian preening varies among sites on the host. The study relies
      on the simple idea that the effectiveness of preening behavior to control lice
      can be quantified by the removal rate of dead lice glued onto the feathers of
      living birds. Two treatments were done to document site-specific differences in
      the efficiency of preening for louse control. The first treatment showed that
      lice disappear from the underwing covert feathers significantly more than from
      the tail feathers. A second treatment showed that preening was responsible for
      the differential removal of lice. There seems to be some correspondence in the
      site specificity of the louse species Columbicola columbae and that of the
      efficiency of preening by the host, which is the feral pigeon (Columba livia).

PMID- 8277396
TI  - Synonymy of Eimeria larimerensis with Eimeria lateralis.
AB  - Oocysts of Eimeria lateralis were isolated from feces of Spermophilus
      richardsonii and compared to published descriptions of E. lateralis and Eimeria
      larimerensis from other spermophiline rodent hosts. A comparison from other
      spermophiline rodent hosts. A comparison of these 2 eimerian species, combined
      with an examination of host specificity of spermophiline eimerians and host and
      parasite distributions, suggests that E. larimerensis is synonymous with E.
      lateralis.

PMID- 8277397
TI  - Eimerian guilds (Apicomplexa: Eimeriidae) in Richardson's (Spermophilus
      richardsonii) and Wyoming (Spermophilus elegans) ground squirrels.
AB  - Feces of Richardson's ground squirrels (Spermophilus richardsonii) were examined
      to determine occurrence and prevalence of eimerian species and to compare guilds
      in these hosts to previously described guilds from Wyoming ground squirrels
      (Spermophilus elegans). Six species of Eimeria were collected from 100
      Richardson's ground squirrels: Eimeria beecheyi (36% infected); Eimeria
      bilamellata (13%); Eimeria callospermophili-Eimeria morainensis complex (41%);
      Eimeria lateralis (6%); and Eimeria spermophili (9%). The species composition and
      prevalences were essentially identical in the 2 congeneric hosts. Three species
      were consistently more (> 30%) and 3 were consistently less (< 20%) prevalent in
      both host species. Furthermore, in both squirrel species the rare species were
      more prevalent in juveniles. Eimerian guilds such as these may be common to many
      species of ground-dwelling sciurid squirrels. The report of E. beecheyi in
      Richardson's ground squirrel constitutes a new host record for this species.

PMID- 8277398
TI  - Unusual gingival enlargement with rapidly progressive periodontitis. Report of a
      case.
AB  - A 15-year-old female patients suffered from recurrent unusual enlargement of the
      gingiva together with rapidly progressive alveolar bone loss. The enlarged
      gingiva completely covered her anterior teeth and protruded from the mouth.
      Marked inflammatory edematous tissue, which predominantly contained plasma cells,
      was observed in the connective tissue. Rapidly progressive alveolar bone loss was
      observed radiographically. The serum antibody titer to Porphyromonas gingivalis,
      measured by ELISA, was much higher than that in healthy individuals. The
      diagnosis was unusual gingival enlargement with rapidly progressive
      periodontitis. Conventional periodontal therapy, including plaque control,
      scaling, root planing, and surgical removal of the soft tissue, did not produce
      complete healing of the gingival lesion, although recurrence of gingival
      enlargement and further loss of the periodontal attachment level were well
      controlled. After the periodontal treatments, the serum antibody titer to P.
      gingivalis decreased to normal levels. This unusual gingival enlargement was
      considered due to systemic factors that exaggerated the gingival response to
      local irritation and altered the usual clinical features of chronic gingivitis;
      local plaque irritation produced the extensive and recurrent enlargement of the
      gingiva. Under these circumstances, infection or overgrowth of periodontopathic
      bacteria, including P. gingivalis, might occur and the alveolar bone loss would
      then advance very rapidly.

PMID- 8277399
TI  - A clinical comparison of collagen membranes with e-PTFE membranes in the
      treatment of human mandibular buccal class II furcation defects.
AB  - Guided tissue regeneration procedures using non-resorbable expanded
      polytetrafluoroethylene (e-PTFE) membranes have become accepted therapy in
      treating moderate furcation defects. Resorbable collagen membranes have also been
      found to support regeneration and preclude the need for surgical removal. The
      present study compares their effectiveness with e-PTFE membranes in treating
      human mandibular Class II buccal furcation defects over a 12-month healing
      interval. Twelve patients were treated with collagen membrane in one defect and e
      PTFE in another. Vertical and horizontal defect repair was evaluated through soft
      tissue probings and hard tissue measurements. Gingival indices and crevicular
      fluid flow measurements were used to evaluate site inflammation. Intragroup
      comparisons were made from baseline to 12 months for each type of membrane (sign
      test) and for differences between treatment groups with collagen versus e-PTFE
      membranes (Wilcoxon signed rank test). Both materials were effective in gaining
      vertical open probing new attachment and horizontal open and closed probing new
      attachment. Collagen membrane was statistically superior to e-PTFE in gaining
      horizontal open new probing attachment and in reduced levels of inflammation at
      the surgical site from baseline to 4 weeks. However, clinical differences were
      negligible. The intrinsic properties and ease of handling make collagen membranes
      a feasible alternative in guided tissue regeneration procedures.

PMID- 8277400
TI  - Periodontal regeneration of human intrabony defects. IV. Determinants of healing
      response.
AB  - The purpose of this study was to identify factors which might affect the healing
      response in intrabony defects treated with guided tissue regeneration. Selected
      sites presented with deep periodontal lesions with 1, 2, and 3 wall combination
      intrabony component of 6.1 +/- 2.5 mm. The significance of patient, tooth, and
      defect characteristics and surgical parameters as predictor variables affecting
      the regenerative outcome before and following the removal of the barrier membrane
      was assessed. Outcome was measured as tissue gain under the membrane, regenerated
      probing attachment level (PAL), and bone fill. The total depth of the intrabony
      component and the radiographic defect angle significantly affected the amount of
      tissue gain. Seventy-five percent (75%) of the variability of regenerated PAL and
      bone fill was explained in terms of tissue gain under the membrane, radiographic
      width of the defect angle, full mouth bleeding score, and presence or absence of
      flap coverage of the newly formed tissue. Control of the identified predictor
      variables might improve the extent and predictability of guided tissue
      regeneration in the treatment of deep intrabony defects.

PMID- 8277401
TI  - Safety testing of a new electronic toothbrush.
AB  - While there have been major advances in understanding the causes and treatments
      of the inflammatory periodontal diseases in the past decade, there is still high
      reliance on the patient to prevent progression of disease through daily oral
      hygiene, primarily toothbrushing and flossing. A new electronic toothbrush, which
      produces mild fluid cavitation as well as rapid fluid streaming, has been
      developed and has shown promise in the ease and efficacy with which it removes
      plaque. In order to determine the safety of frequent and prolonged use of this
      device, the gingival tissues of 6 mongrel dogs were exposed to excessively long
      daily exposures to this toothbrush for up to 2 months. Each quadrant of each
      dog's mouth was randomly assigned a different treatment: no brushing, manual
      brush 1.0 minute, electronic brush 1.0 minute, or electronic brush 7.5 minutes.
      The dogs were examined weekly by a periodontist who was blinded to the
      treatments. Plaque scores and bleeding on probing scores were calculated, and
      possible gingival irritation was monitored carefully. At the end of the trial
      gingival biopsies taken from all the test areas. These were processed for
      conventional histopathologic evaluation and examined by an oral pathologist who
      was also blinded as to the treatments. The results showed that brushing a single
      posterior segment of teeth for 7.5 minutes daily for 2 months with the electronic
      brush did not result in any clinically or histologically evident damage to the
      gingiva. Rather, the areas so treated showed excellent health as determined by
      both clinical and histologic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277402
TI  - Radiographic attachment in periodontitis-prone teeth with endodontic infection.
AB  - The purpose of the present investigation was to examine the influence of a root
      canal infection on radiographic attachment. In addition, influence of the quality
      of the root fillings as well as the size of the periapical radiolucencies were
      studied. The investigation was conducted as a retrospective study on a
      consecutive referral population. The periapical conditions in endodontically
      involved single-rooted teeth from a selected patient sample were correlated to
      the periodontal status of the teeth. Teeth with periapical lesions were found to
      have lost significantly more radiographic attachment, approximately 2 mm. A
      comparison between pocket depth in teeth with and without periapical pathology
      consistently showed that periapical pathology was significantly correlated to an
      increased pocket depth, also after adjusting for differences in radiographic
      attachment. It was concluded that periodontitis-prone teeth run a significantly
      higher risk of losing periodontal attachment if a root canal infection is also
      present and evident as a periapical radiolucency.

PMID- 8277403
TI  - Success rates of osseointegration for implants placed under sterile versus clean
      conditions.
AB  - A retrospective analysis was done comparing the success rate of osseointegration
      at stage 2 of implants placed under "sterile" versus "clean" conditions.
      "Sterile" surgery took place in an operating room setting with strict sterile
      protocol. "Clean" surgery took place in a clinic setting with the critical factor
      that nothing touched the surface of the implant until it contacted the prepared
      bone site. A total of 273 implants in 61 cases were placed under sterile
      conditions with a fixture success rate of 98.9% and a case success rate of 95.1%;
      113 implants were placed under clean conditions in 31 cases with a fixture and
      case success rate of 98.2% and 93.5%, respectively as judged clinically at stage
      2. The difference in the success rates was not statistically significant. The
      results of this analysis indicate that implant surgery can be performed under
      both "sterile" and "clean" conditions to achieve the same high rate of clinical
      osseointegration.

PMID- 8277404
TI  - Periodontal status of women taking postmenopausal estrogen supplementation.
AB  - The association between supplementary estrogen intake and periodontal and
      gingival status in a total of 228 women 50 to 64 years of age was examined.
      Clinical parameters including visible supragingival plaque, subgingival calculus,
      probing pocket depth, clinical attachment level, alveolar bone height
      measurements, and number of remaining teeth were measured. Gingival status was
      recorded as gingival bleeding after gentle manipulation. Selected periopathogens,
      socio-economic, demographic, smoking habits, and health care variables were
      assessed. Gingival bleeding was significantly lower in the estrogen supplement
      group (n = 57) compared to the control group (n = 171) (P = 0.009); the estrogen
      group also exhibited significantly lower visible plaque levels (P = 0.030) and
      fewer Capnocytophaga-ssp. (P = 0.032). Dental care was more frequent (P < 0.001),
      and education levels were higher (P = 0.022) in the estrogen group. To
      investigate whether differences among the above parameters contributed to the
      difference in gingival bleeding, an age-adjusted analysis of covariance (ANCOVA)
      was used. The final ANCOVA indicated non-significant relationships for all
      parameters examined except estrogen intake (P = 0.044). Women taking estrogen
      exhibited lower gingival bleeding than the control group after correcting for
      these factors. The results indicate that estrogen supplementation is associated
      with less gingival bleeding in women aged 50 to 64, as compared to an age-matched
      control group.

PMID- 8277405
TI  - Abnormal proportion of gamma delta T cells in peripheral blood is frequently
      detected in patients with periodontal disease.
AB  - The proportions of gamma delta T cells in the peripheral blood of 8 early-onset
      periodontitis (EOP) patients, 8 later-onset periodontitis (LOP) patients, and of
      17 healthy subjects (HS) were assessed by immunofluorescence assay using an anti
      pan gamma delta T cell monoclonal antibody (TCR-delta 1) to study the population
      attributes of peripheral blood gamma delta T cells in patients with periodontal
      disease. The distribution of the proportions of gamma delta T cells in both EOP
      and LOP patients was found to be one and one half times broader than that in the
      HS; however, there was no significant difference in the proportion of gamma delta
      T cells between each group. An abnormally high proportion of peripheral blood
      gamma delta T cells in pan T cells (> 9.90%) was observed in 37.5% of both the
      EOP patients and the LOP patients. An abnormally low proportion (< 5.57%) was
      observed in 50% of the EOP patients and in 25% of the LOP patients. The higher
      occurrences of the high or low gamma delta T cell proportions were significant
      between EOP and HS, and between EOP+LOP and HS. There was no correlation between
      the proportion of gamma delta T cells and age or the clinical parameters of
      periodontal status. It was concluded that an abnormal proportion of gamma delta T
      cells is frequently detected in patients with periodontal disease. These findings
      are consistent with the proposed role of the gamma delta T cells for playing a
      unique role as a first line defense against infections at body surfaces.

PMID- 8277406
TI  - Guided tissue regeneration and anti-infective therapy in the treatment of class
      II furcation defects.
AB  - The purpose of the present study was to evaluate the effect of anti-infective
      therapy on the success of periodontal regeneration in mandibular Class II
      furcation defects. Eighteen patients with mandibular bilateral Class II furcation
      defects were enrolled. Following an initial hygienic phase, guided tissue
      regeneration (GTR) was performed using an expanded polytetrafluoroethylene (e
      PTFE) membrane barrier. The area was surgically exposed, thoroughly root planed,
      and irrigated with either tetracycline (100 mg/ml) or 0.9% saline. Post-operative
      care included systemic tetracycline (250 mg q.i.d.) and chlorhexidine 0.12%
      mouthwash twice daily. Patients were maintained on a prophylaxis schedule of
      every 2 weeks for the first 3 months, and monthly thereafter. Clinical parameters
      of probing depth (PD), probing attachment level - vertical (PAL-v), probing
      attachment level - horizontal (PAL-h), and target periodontal pathogens were
      monitored at baseline and quarterly for one year. An overall improvement in all
      clinical parameters was observed in both groups: probing reduction (3.1 mm), PAL
      h gain (2.3 mm), and PAL-v gain (1.2 mm) were all statistically significant
      compared to baseline measurements. Vertical measurements were performed parallel
      to the long axis of the tooth with no attempt to angulate the probe into the
      furcation. There was no significant difference in sites receiving tetracycline. A
      strong positive correlation was noted between initial PD and pocket reduction (r
      = 0.77, P < 0.0001) and between initial PD and PAL-h gain (r = 0.54) and PAL-v
      gain (r = 0.45) suggesting that initial probing depth might be used to assess the
      regenerative potential of a given site.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277407
TI  - HLA-D and T lymphocyte reactivity to specific periodontal pathogens in type 1
      diabetic periodontitis.
AB  - Bacterial antigen fragments complexed with class II major histocompatibility
      molecules (HLA-D) on antigen presenting cells (APCs) stimulate CD4+ T lymphocyte
      proliferation, presumably to protect the host. This study examined these
      responses to antigens of two periodontal pathogens in four groups (n = 15) of age
      (young adult) and sex-matched Caucasian subjects with or without type 1 diabetes
      and moderate to severe periodontitis: Group DP = diabetics with periodontitis;
      Group DnP = diabetics without periodontitis; Group nDP = nondiabetics with
      periodontitis; and Group nDnP = nondiabetics without periodontitis. HLA-D
      phenotypes for each subject were determined by lymphocytotoxicity assays. T
      lymphocytes purified from peripheral blood were stimulated in cell culture with
      APC pulsed with various concentrations of tetanus toxoid, Porphyromonas
      gingivalis, and Capnocytophaga sputigena antigens. T lymphocyte reactivity (3H
      thymidine incorporation) was numerically lower in cultures from diabetics
      stimulated with unpulsed APC (not significant), and antigen-pulsed cultures
      showed low proliferation and no significant differences among groups. Stimulation
      indices in cultures from diabetic patients stimulated with P. gingivalis or C.
      sputigena, however, were significantly elevated at all antigen concentrations
      compared to nondiabetic cultures. The occurrence of HLA-DR4 was moderately
      associated with diabetes (P < 0.05) and highly associated with periodontitis (P <
      0.001, log-linear model for categorical variables); and HLA-DR53 and HLA-DQ3 were
      significantly associated with periodontitis (P < or = 0.02). HLA-DR was crucial
      to lymphocyte stimulation (anti-HLA-DR blocking experiments), but the low
      peripheral blood T cell reactivity to antigens of periodontal pathogens could not
      be linked with HLA-D type or periodontitis susceptibility.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8277408
TI  - Measurements of interleukin-6 in gingival crevicular fluid from adults with
      destructive periodontal disease.
AB  - This paper describes a study of whether or not the amounts of interleukin-6 (IL
      6) in gingival crevicular fluid (GCF) are correlated with periodontal clinical
      measures. A sensitive ELISA was developed to measure IL-6 in GCF. Two male and 3
      female adult subjects with periodontal disease were examined at their first
      appointments, after 3 months, and after 6 months. Data were obtained on plaque
      index (PI), bleeding index (BI), probing depth (PD), and on the IL-6 content of
      GCF samples from 16 sites per subject for a total of 240 measurements.
      Significant correlations were found between BI and IL-6 (P < 0.005) and between
      PD and IL-6 (P < 0.05), but not between PI and IL-6. Only 6 out of the 80 sites
      (in 3 of the 5 subjects) showed PD increases of at least 2 mm. However, for each
      of these 3 subjects, the amounts of IL-6 in the GCF samples from these sites were
      markedly higher than the mean amounts of IL-6 in the GCF samples from the
      remaining sites. These findings suggest that IL-6 may be a useful indicator of
      periodontal disease, although more extensive longitudinal studies are needed to
      determine the real clinical value of this GCF component.

PMID- 8277409
TI  - Surgical treatment of induced peri-implantitis in the micro pig: clinical and
      histological analysis.
AB  - The purpose of this pilot study was to determine if lost osseous support adjacent
      to root form implants could be regenerated using a guided tissue regeneration
      technique. Three fixtures were placed in each edentulous mandibular bicuspid
      region of two micro pigs. A total of 6 fixtures were placed in each pig. Due to
      the presence of a pathologic condition, which was in no way related to the
      research, the results of one pig were not evaluated. Following osseointegration,
      peri-implantitis were induced by the use of ligatures and a soft diet. Three
      modalities of treatment were performed. Utilizing a surgical flap approach, one
      third of the fixtures (one per quadrant) were covered with expanded
      polytetrafluoroethylene (ePTFE) membrane and submerged under the soft tissue
      complex. The second group of fixtures were submerged under the soft tissue
      complex with no ePTFE membrane. The control fixtures along with their abutments
      were debrided and remained non-submerged. All fixtures were debrided using an air
      abrasive polishing system. The osseous defects around the fixtures were measured
      from a fixed reference point at the time of surgery and after obtaining block
      sections.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277410
TI  - Evaluating patient perceptions as short-term outcomes of periodontal treatment: a
      comparison of surgical and non-surgical therapy.
AB  - To quantify patient perceptions of periodontal therapy, we administered a self
      report questionnaire employing a visual analog scale (VAS) to 162 patients
      following surgical and non-surgical treatments. The questionnaire tested for
      variables of pain, sensitivity, swelling, function, altered appearance,
      comparison of postoperative discomfort to restorative treatment (crown or
      filling), discomfort experienced during the procedure, and resultant disability
      days. Tests of reliability indicated that with the exception of thermal
      sensitivity, the variables were significantly reproducible (r > 0.45 for all
      tests, P < 0.002). Analyses of variance indicated that in contrast to non
      surgical treatments, surgery produced significantly more postoperative
      "discomfort" (P < 0.05) for all variables except experience, sensitivity, altered
      speech, and comparison to crown preparation. When analyzed according to the type
      of procedure, soft tissue grafts and osseous surgery produced the most
      postoperative discomfort. Pearson correlation indicated statistically significant
      (P < .0001) relationships between pain-related measures (postoperative pain,
      number of postoperative analgesics, days of pain, days of work missed, and
      sensitivity). Duration of pain was also found to be related to a history of
      periodontal treatment (P < .02), but not to previous restorative treatment. These
      data indicate that patient perceptions of periodontal treatment can be reliably
      measured and may be used to address appropriateness of care issues.

PMID- 8277411
TI  - Effects of a combination therapy to eliminate Porphyromonas gingivalis in
      refractory periodontitis.
AB  - This report describes the clinical and microbiological features of 30 refractory
      patients and their response to a combined local and systemic therapy at 6 weeks
      and 3 years following treatment. The refractory treatment protocol (RefTx)
      consisted of a 2-week regimen of amoxicillin/clavulanate potassium in conjunction
      with professional, intrasulcular delivery of povidone iodine, and chlorhexide
      mouthwash rinses b.i.d. Eighty-seven percent of the patients had favorable
      clinical responses to the RefTx and could be divided into 3 groups (A, B, C)
      based upon initial flora patterns and the shifts that occurred following
      treatment. Pretreatment prevalence of Porphyromonas gingivalis (P.g.) was 36.7%.
      The RefTx was effective in reducing P.g. below detection levels in 10 of the 11
      positive patients at P < 0.01; each of these 10 patients (Group A) demonstrated
      significant gain in attachment. Other black-pigmented Bacteroides species (OBP)
      were isolated from 70% of the patients at baseline. Nine of these patients did
      not harbor P.g., showed clinical improvement upon treatment, and were OBP
      negative following treatment (Group B). Group C patients (7) demonstrated
      clinical improvement with therapy and did not fit into either Group A or B based
      upon microbial patterns. Group D patients (4) did not show clinical improvement
      with 3 patients harboring either P.g. or OBP after treatment. The RefTx was
      effective at reducing probing pocket depth with a 56% decrease in the number of
      pockets greater than 6 mm at 6 weeks. This was accompanied by an overall gain of
      > or = 1 mm of probable attachment in 45% of all sites. The clinical effects of
      the RefTx were shown to persist at 34.3 months with an apparent attachment gain
      of > or = 1 mm in 41.2% of sites. These data suggest that P.g. and OBP are
      important pathogens in refractory periodontitis and that the RefTx protocol is an
      acceptable, non-invasive alternative for the management of these patients.

PMID- 8277412
TI  - Relationships between dietary minerals and plasma lipids and glucose among older
      adults.
AB  - This study evaluated the relationships between dietary minerals and plasma lipids
      and glucose of forty-three adults, age 60 and above. Subjects self-selected diets
      averaged 33% of calories from fat, and 205 mg of cholesterol per day. Plasma
      total cholesterol, HDL-cholesterol, triglycerides and glucose were determined
      enzymatically, and LDL-cholesterol was calculated. Plasma lipid values for
      subjects with dietary mineral intakes less than 2/3 of the RDA were compared to
      those with intakes greater than 2/3 of RDA. With lower copper intakes plasma
      triglycerides were elevated (p < or = 0.05). Both plasma total cholesterol and
      LDL-cholesterol were elevated with lower zinc intakes (p < or = 0.05). LDL
      cholesterol was elevated with lower calcium intakes (p < or = 0.05) and with
      lower magnesium intakes fasting glucose was elevated (p < or = 0.05). No
      significant differences were observed in plasma lipids due to dietary fat,
      saturated fat or cholesterol intakes. In these older adults, dietary mineral
      intakes showed more relationships to plasma lipid parameters than did amount or
      composition of dietary fat or cholesterol.

PMID- 8277413
TI  - Commercial frozen meals: a cost-effective alternative for home-delivery in
      feeding programs for the elderly?
AB  - The costs of eight commercial and eight congregate-site frozen meals were
      compared in this study. Only half of the congregate-site meals were cheaper on a
      per ounce basis. The average cost per ounce of all eight congregate-site meals
      was only one cent less than that of the commercial meals. Preference data,
      collected previously from elderly participants, indicated significantly higher
      preference for four of the eight commercial meals. Commercial meals with the
      highest preference ratings also were less costly per ounce than the corresponding
      congregate-site meals. Results suggest that commercial frozen meals could be a
      cost-effective alternative for nutrition programs offering home-delivered meals.

PMID- 8277414
TI  - A survey of food service managers of washington state boarding homes for the
      elderly.
AB  - Menus provided by food service managers of boarding homes for the elderly in
      Washington State were analyzed for nutrient content and frequency with which
      disease preventive foods were offered. Nutrition knowledge and flexibility of
      attitudes were measured among the food service managers. Forty-three homes
      responded. More than half of menus provided by homes exceeded Recommended Dietary
      Goals for saturated fat, sodium and cholesterol by 33%. Over 60% of menus were
      deficient (less than 67%) compared to the RDA for zinc, copper and magnesium.
      Nutrition knowledge and attitude scores of food service managers were not
      significantly correlated to the frequency with which disease preventive foods
      were served. Future opportunities for nutrition education should aim at
      increasing the ability of food service managers to transfer nutrition knowledge
      into menu planning skills.

PMID- 8277415
TI  - Dietary intake and health habits of healthy, retired, elderly men.
AB  - Retired, non-sedentary, elderly men (66 to 80 years) participated in this study.
      Three-day food records, one-week records of daily physical activity and
      information on health habits and medical and physical activity status were
      obtained. Analysis of the food records showed a mean total energy intake of 2040
      +/- 461 (SD), with carbohydrates contributing 46.7 +/- 10.8% of total energy, fat
      34.3 +/- 8.9%, protein 16.9 +/- 3.1%, and alcohol 1.9 +/- 2.7%. Mean consumption
      of the selected nutrients studied were above the Recommended Dietary Allowances
      (RDA). The mean activity level in a typical week was 14.6 +/- 6.8 Cooper points.
      Results of this study suggest that maintaining physical activity and consuming a
      nutritionally adequate diet may contribute significantly to the maintenance of
      health and well-being among the elderly and may delay the deterioration of
      functional capacity which accompanies the normal process of aging.

PMID- 8277416
TI  - What's your IQ on nutrition education for older adults?
AB  - This IQ test asks practitioners to designate true or false to a series of ten
      statements on nutrition education for older adults. The correct responses are
      given, along with detailed explanations for the responses. Topics which are
      explored include: how to offset hearing and visual defects among older adults,
      how to improve the relevance of nutrition education by touching their hot
      buttons, and how to provide a learning environment which improves retention. A
      summary of the seven principles for effective nutrition education for older
      adults is presented.

PMID- 8277417
TI  - Living with OBRA--nutritional assessment and review.

PMID- 8277418
TI  - Influence of selected psychosocial factors on dietary intake in the elderly.
AB  - The rapidly increasing elderly population in the United States is causing
      mounting concerns about their health and well-being. Diet is an important part of
      health. The objective of this study was to see if gender, marital status and
      congregate meal participation influenced dietary intake in the non
      institutionalized elderly. The randomly selected 290 elderly men and women were
      interviewed using food frequency and diet history methods. Men had a better
      nutrient intake than women for selected nutrients. Single elderly of both sexes
      had a better nutrient intake than the married elderly. Congregate meal
      participants had a poorer nutrient intake than the non-participants.

PMID- 8277419
TI  - Nutrition screening practices in adult day care centers: a national survey.
AB  - Older adults have been identified as one of the largest groups at risk of
      malnutrition in America and represent the target population of the Nutrition
      Screening Initiative. At the University of Delaware Adult Day Care Center,
      nutrition screening is an integral component of basic services provided to
      clients and their caregivers. To determine the extent of current nutrition
      screening practices in other adult day care centers, centers across the United
      States were surveyed. A total of 160 centers (53%) responded; 101 indicated
      nutrition screening was an on-going service. A number of differences and
      similarities in nutrition screening parameters was evident. Most centers
      responding assessed the following parameters: food intolerance, medical history,
      weight, height, swallowing difficulties, and bowel habits. Hematological
      parameters and other anthropometric measurements were evaluated with least
      frequency. Interest in nutrition screening appeared great. Further research
      should examine relationships between nutrition screening and other factors such
      as staffing patterns, center settings, and funding sources.

PMID- 8277420
TI  - Nutritional care of ambulatory residents in special care units for Alzheimer's
      patients.
AB  - The availability and an assessment of the nutritionally-relevant information from
      100 medical records of ambulatory residents in ten special care units (SCU) for
      Alzheimer's patients was determined. Eight facilities had estimated calorie and
      fluid needs and four estimated protein needs of residents. Over 40% of the
      residents were underweight and significant weight loss was reported for 20%.
      Values for hemoglobin, hematocrit, albumin and cholesterol were available on 61,
      60, 36, and 25% of the patients, respectively. Hemoglobin, hematocrit and albumin
      were 8% lower and cholesterol was 24% higher than the levels associated with high
      death rates among institutionalized elderly. Many factors existed placing
      patients at high risk for malnutrition. Staff at all the facilities monitor the
      nutritional status of Alzheimer's patients to a variable extent.

PMID- 8277421
TI  - Attitude changes of dietetic students performing nutritional assessment on
      healthy elderly.
AB  - As the population of individuals over 65 yrs of age continues to grow, so does
      the demand for nutrition counseling and intervention for this age group. Dietetic
      students traditionally have minimal exposure to groups of healthy elderly yet
      entry level dietitians must effectively interact with these groups immediately
      upon employment. Attitudes and perceptions held by dietetic students about the
      elderly are important to their professional development and may affect the
      quality of care these students provide in the future. This study investigated
      attitudes of dietetic students before and after a short, direct experience with a
      group of elderly. Students had a significant positive change in attitudes as a
      result of interacting with the older adults.

PMID- 8277422
TI  - The nursing home group dining room: managing the work of eating.
AB  - The purpose of this study was to describe the observed experiences and resident
      perceptions of a nursing home group dining room. Data collection for the
      qualitative study was done using participant observation in a large group dining
      activity and in-depth interviews with 10 residents. Using the constant
      comparative method of data analysis, a model was generated from the data called
      Managing the Work of Eating. This model included the specific tasks or challenges
      of eating in the group dining room. Major categories of the model included:
      Negotiating the Environment, Coping with Frailty, Dealing with Colleagues, and
      Responding to the System. Implications for practice include development of
      strategies designed to promote resident independence and avoid excess disability.

PMID- 8277423
TI  - The quality of survey data obtained from elderly adults.
AB  - The quality of survey data obtained from elderly adults has important
      implications for nutrition status assessment, policy decisions and program
      development. Self-reported information by adults of all ages is subject to
      inaccuracies. Accuracy of data obtained from older respondents may be lower than
      that of younger respondents. Errors made by older adults are largely due to
      misinterpretation of the questions asked, motivations related to participation
      and reporting of information, and changes in memory associated with aging and
      other factors which may impact respondent accuracy. Cooperative efforts by
      cognitive psychologists, survey researchers and nutritionists are necessary for
      improving both questionnaire design and the accuracy of information obtained.

PMID- 8277424
TI  - Cheese acceptance and dairy product consumption in an older population.
AB  - This study examined the acceptability of cheese products in a population of older
      adults in relation to their consumption of dairy products. The majority of the
      subjects liked hard cheeses (Cheddar, Provolone and Swiss) more than soft,
      ripened cheeses (Brie and blue cheese), and showed no significant difference in
      preference between regular and lowfat or fat-free processed cheese. A positive
      correlation was found between hedonic ratings and frequency of consumption across
      the five cheeses evaluated in the study. Almost one-half of the participants
      considered cheese to be a high calorie, high fat and high cholesterol food. This
      study suggests that lowfat or fat-free cheese products in the form of mild, hard
      or processed cheeses could successfully be incorporated in the diet of older
      adults to implement current dietary guidelines for fat and calcium consumption.

PMID- 8277425
TI  - Serve Our Seniors, Inc.--a demonstration program for proposed California menu
      guidelines for senior nutrition. California Department of Aging.
AB  - Revised menu guidelines, written by the California Department of Aging (CDA) for
      senior nutrition programs, were tested by Serve Our Seniors, Inc. in a
      demonstration program from January '91 through June '92. Results showed improved
      nutrient value of the meals through increasing fiber, and decreasing sugar and
      fat. New menus were accepted by senior participants with little resistance.
      Project food costs increased 4%. Guidelines were used in a variety of project
      kitchens, with minimal staff training. Limited storage was a problem. Vendors
      were encouraged to identify appropriate foods and control costs.

PMID- 8277426
TI  - Surviving a nursing home strike: a case study in emergency planning.

PMID- 8277427
TI  - [Biliary metabolites of levonorgestrel in rats].
AB  - The metabolism of levonorgestrel (LNG) in the bile following oral administration
      of the drug was examined in female rat. 1) Within 48 h after administration of
      14C-labelled LNG (LNG-14C), 67-82% of the radioactivity was excreted into the
      bile. 2) Almost all the metabolites in the bile were conjugated with glucuronic
      acid or sulfuric acid and only a small amount of the unchanged compound was
      found. 3) After treatment of these metabolites in the bile with beta
      glucuronidase and arylsulfatase, more than ten aglycones were detected on TLC.
      Three main aglycones, M1, M2 and M3, were isolated. They accounted for 68.0, 0.8
      and 11.5% of the radioactivity excreted into the bile, respectively. 4) The
      structures of M1 and M2 were assumed to be 13-ethyl-18,19-dinor-5 alpha,17 beta
      pregn-20-yne-3 alpha,17- diol and 13-ethyl-18,19-dinor-5 beta,17 beta-pregn-20
      yne-3 alpha,17-diol, respectively, by NMR and LC/MS analyses, and confirmed by
      direct comparison with respective authentic samples. M3 was assigned to be 13
      ethyl-18,19-dinor-5 alpha,17 beta-pregn-20-yne-3 alpha,16 beta,17-triol by NMR,
      LC/MS and GC/MS analyses and acetonide derivation. 5) Isolation of the
      glucuronide metabolite, M4, from the bile, was achieved by column chromatography
      using Amberlite XAD-2 and Sephadex LH-20. Hydrolysis of this compound with beta
      glucuronidase released M1 and glucuronic acid. After M4 was converted to an
      acetylated-methyl ester derivative, the definite structural assignment of M4 was
      established to be M1-3-O-yl glucuronic acid by NMR analysis. The NOE effect and
      the value of the corresponding coupling constant of the anomeric proton showed
      that the glucoside moiety was in the beta configuration. These findings suggested
      that LNG was predominantly converted to 5 alpha-reduced metabolites and that the
      5 beta-metabolite accounted for less than 1% of the total metabolites in female
      rats. These metabolites were excreted as glucuronides into the bile.

PMID- 8277428
TI  - [Separation of glycoproteins from cyst fluids of human ovarian cystomas in benign
      and their some chemical and serological properties].
AB  - Perchloric acid-soluble fractions (PASFs 1-3) which were obtained from cyst
      fluids of two patients [(Nos. 1 (blood group B) and 2 (blood group A))] with
      ovarian mucinous cystadenoma and one patient (No. 3 (blood group A)) with ovarian
      dermoid cyst in benign, were identified as glycoproteins by their chemical
      composition analyses, respectively. Reactivities of PASFs 1-3 against blood group
      anti-sera and lectins suggest that these PASFs did not contain MN blood group
      substances, Vgu glycoproteins and T-active glycoproteins. PASF 1 was separated
      into 11 fractions by Sephacryl S-500 gel filtration. From chemical composition,
      SDS-PAGE and serological property of the main fraction (Fr. 5), other one
      fraction (Fr. 7) and mild acid hydrolysates of these two fractions, it is
      possible to presume that PASF 1 consisted of a large number of AB-active and
      fucose-rich glycoproteins with high molecular weights and some of these
      glycoproteins bear either NeuNAc alpha 2-->6GalNAc (sialyl Tn) group or both
      sialyl Tn and sialylated T groups.

PMID- 8277429
TI  - [Pharmacological studies on human urinary kallidinogenase (SK-827): cerebral
      protective effects].
AB  - We investigated the cerebral protective effects of human urinary kallidinogenase
      (SK-827) in rabbits. The following results were obtained: 1) At a dose of 5.0 x
      10(-3) to 1.25 x 10(-2) PNA U/kg, SK-827 significantly inhibited the decrease of
      focal cerebral blood flow and the impairment of electrocorticogram (ECoG)
      activity in infarcted rabbits. 2) SK-827 at a dose of 2.5 x 10(-3) PNA U/kg
      inhibited the development of infarction area induced by internal carotid arterial
      injection of glass beads. 3) SK-827 at a dose of 2.5 x 10(-3) to 5.0 x 10(-3) PNA
      U/kg inhibited the decrease of cerebral cortical pO2 induced by 5% oxygen
      inhalation. 4) On subacute phase 7 days after the destruction of internal
      capsule, SK-827 at a dose of 1.25 x 10(-2) PNA U/kg improved the abnormality of
      spontaneous ECoG. These findings suggest that SK-827 minimizes the reduction of
      cerebral function induced by ischemia.

PMID- 8277430
TI  - [Screening test of crude drug extract on anti-HIV activity].
AB  - The anti-HIV-1 effects of 204 crude drugs of common use in Japan were evaluated
      in vitro. As a result, 45 samples inhibited HIV-1-induced cytopathogenicity in MT
      4 cells. In particular, the hot water extracts of Lithospermum erythrorhizon
      (root) and Prunella vulgaris (spike) showed the strongest anti-HIV-1 activities.
      Their IC100 values were both 16 micrograms/ml. In general, the hot water extracts
      of the crude drug suppressed the replication of HIV-1 growth more strongly than
      the cold water extracts.

PMID- 8277431
TI  - [Pharmacological studies on human urinary kallidinogenase (SK-827): effects on
      cerebral metabolism].
AB  - We investigated the effects of human urinary kallidinogenase (SK-827) on cerebral
      metabolism in normal and infarcted rabbits. SK-827 did not influence cerebral
      glucose and oxygen uptake in normal rabbits. In infarcted rabbits, cerebral
      glucose and oxygen uptake significantly decreased. SK-827 tended to inhibit the
      decrease of cerebral blood flow, and significantly inhibited the decrease of
      cerebral glucose and oxygen uptake in infarcted rabbits. Thus, SK-827 improved
      cerebral glucose metabolism in infarcted rabbits.

PMID- 8277432
TI  - [Progress and new findings on the method of selective stimulation of utricular
      nerve].

PMID- 8277433
TI  - [Differentiational profiles of skeletal muscle internal membrane systems directly
      related to excitation-contraction coupling].
AB  - The arrangements of internal membrane systems (transverse (T) tubules,
      sarcoplasmic reticulum (SR) and T-SR junction (triad)) are matched to contractile
      profiles in adult muscle fibers. The developmental profiles of the these internal
      membrane systems directly related to the excitation-contraction (EC) coupling
      were investigated in the chicken anterior (ALD, slow) and posterior (PLD, fast)
      latissimus dorsi muscles in ovo (14 to 21 days incubation: E 14-E 21) and after
      hatching (1 to 30 days after hatching: D 1-D 30). These internal membrane systems
      were visualized using confocal and electron microscopes. ALD and PLD have similar
      contraction time in early developmental stage (E 14-E 16), however, PLD suddenly
      becomes faster at E 17-E 18. Following the differentiation of faster contraction
      properties (E 18-E 19), density of triads increased significantly in PLD. Early
      development of T-tubules, on the other hand, is quite similar in both ALD and
      PLD. Peripherally located, longitudinally oriented T tubules, and the first T
      networks crossing the fiber center appear earlier in ALD (E 14-E 16) than PLD,
      but have similar dispositions. The final fiber type specific disposition of T
      tubules is established after hatching, and three major components of the E-C
      coupling pathway are in place as soon as myofibrils develop.

PMID- 8277434
TI  - Intracoronal incisal splint.
AB  - An intracoronal incisal splint for the stabilization of mobile anterior teeth is
      described. Advantages of the technique are good esthetics, open embrasures and no
      disturbance of occlusion.

PMID- 8277435
TI  - Potassium nitrate-zinc oxide eugenol temporary cement for provisional crowns to
      diminish postpreparation tooth pain.
AB  - Pulpal injury commonly occurs with tooth preparation for complete fixed partial
      dentures. This can be documented by the substantial incidence of pain after tooth
      preparation. In this study, a 4% potassium nitrate-zinc oxide eugenol temporary
      cement was used to secure provisional crowns over recently prepared teeth and it
      significantly reduced the incidence and severity of pain after tooth preparation
      and impression taking.

PMID- 8277436
TI  - Stimulated parotid gland flow rates in healthy, elderly dentulous and edentulous
      individuals.
AB  - The use of dentures has been associated with increased stimulated parotid
      salivary flow rates (SPFR). A comparison of SPFRs was made between dentulous
      subjects having 20+ teeth (n = 190) and edentulous individuals (n = 67). Two
      different populations were selected, a white group from the Baltimore
      Longitudinal Study of Aging and an African-American group from the Washington
      Village Medical Center in Baltimore. Each group was healthy and unmedicated and
      had a mean age of 70.2 years. SPFR was determined with a Carlson-Crittenden cup
      and 2% citrate for stimulation. The edentulous subjects did not wear their
      dentures during salivary collection. The results indicated a significantly lower
      SPFR in dentate individuals compared with edentulous subjects (p < 0.01).
      Dentulous men also had a lower SPFR than edentulous men (p < 0.04). In addition,
      a pre- and postsurgical evaluation of 10 individuals who underwent full mouth
      tooth extractions revealed no differences in SPFR. These results suggest that
      edentulism per se does not have a deleterious effect on stimulated parotid
      salivary flow rates.

PMID- 8277437
TI  - Evaluation of three occlusal examination methods used to record tooth contacts in
      lateral excursive movements.
AB  - Accurate and repeatable methods for recording tooth contacts are required for the
      clinical management of problems related to occlusion. A thorough understanding of
      the materials and procedures used in these methods is important to achieve
      desirable results in the treatment of such problems. This study compared three
      occlusal examination methods to determine the influence of materials and
      procedures on the number of tooth contacts recorded. Tooth contacts were analyzed
      at two lateral mandibular positions with each method. It was found that the
      method that uses black silicone recorded the highest number of tooth contacts.
      Thus the most frequent type of occlusal pattern observed was full-balanced
      occlusion. This study suggested that the disparities of results reported in
      literature on occlusal contact patterns could be the result of the different
      materials and methods used for occlusal registration.

PMID- 8277438
TI  - New implant surgical guide.
AB  - This article describes the process of making and using a surgical guide stent. It
      is intended to enable the surgeon to maintain the same horizontal and vertical
      axes of cylindrical endosseous implants during the surgical phase of implant
      placement as those determined at the treatment planning stage. Furthermore, the
      stent can be used with the entire series of surgical drills, thereby minimizing
      the chance of inadvertently enlarging the implant site as a result of freehand
      use of the handpiece.

PMID- 8277439
TI  - Esthetic inserts for implant prostheses.

PMID- 8277440
TI  - Natural tooth intrusion and reversal in implant-assisted prosthesis: evidence of
      and a hypothesis for the occurrence.
AB  - Based on clinical observation, a hypothesis of the mechanism of intrusion of
      natural teeth in an implant-assisted prosthesis is suggested. Engineering
      principles are presented that establish an energy absorption model as it relates
      to the implant-assisted prosthesis. In addition, in the course of patient
      treatment it has been discovered that the intrusion of natural teeth can be
      reversed. Patient histories that demonstrate intrusion reversal are reviewed. The
      possible mechanisms for the intrusion/reversal phenomenon are presented and
      preventative recommendations are given.

PMID- 8277441
TI  - Temporomandibular joint axiography and MRI findings: a comparative study.
AB  - Axiography may be useful in the evaluation of condyle motion and the effects of
      internal derangements on this motion. Fifty-one patients were selected by one
      investigator (RHT) to provide a representative sample of asymptomatic and
      symptomatic subjects for the following categories: (1) normal disk position, (2)
      disk displacement with reduction, (3) disk displacement without reduction and (4)
      disk displacement without reduction associated with degenerative joint disease.
      Axiography was performed by a separate investigator (KGP) in a blinded fashion.
      The diagnosis of the presence of internal derangement was based on the tracings
      only. All subjects had bilateral magnetic resonance imaging scans to evaluate for
      the presence or absence of internal derangement. The diagnostic sensitivity was
      0.64, which indicated that axiography is marginal at identifying disease when
      present. The negative predictive value was 0.78, which indicated that axiography
      is accurate in the detection of normal disk condyle relationship.

PMID- 8277442
TI  - Effects of disinfecting irreversible hydrocolloid impressions on the resultant
      gypsum casts: Part III--Dimensional changes.
AB  - This study evaluated the effect of disinfection time (10, 30 and 60 minutes) on
      the dimensional changes of stone casts poured against an irreversible
      hydrocolloid impression material (Jeltrate). Impressions were made of a stainless
      steel analog of a maxillary arch. The impressions were sprayed with bleach,
      iodophor, phenol, and water and were stored for designated times before poured in
      a type IV stone (Vel-mix). The arch width, length, and depth of the vault of the
      resultant casts were measured by use of a contact measuring device (MicroVal)
      capable of measuring to 0.0001 mm. Data were analyzed with two-way analysis of
      variance at the 95% confidence level. Results indicated that disinfection
      treatment of alginate impressions with surface disinfectants did not cause
      significant dimensional changes in the resultant stone casts from statistical and
      clinical points of view.

PMID- 8277443
TI  - Practical denture disinfection.
AB  - Dental laboratory personel are at risk of contracting infections from dental
      prostheses that have not been properly disinfected. A 4% chlorhexidine scrub for
      15 seconds followed by a 3-minute contact time with a chlorine dioxide solution
      was effective in disinfecting contaminated dentures. Chair-side disinfection of
      dental prostheses before laboratory procedures is the key to keeping microbial
      contamination out of the dental laboratory.

PMID- 8277444
TI  - Cast metal bars used for laboratory processing of bar-supported prostheses.
AB  - The procedure described uses cast metal bars in the master cast to ensure cast
      strength and accuracy in processing, rebasing, relining, or repairing bar
      supported removable prostheses. This method has been found to be an easy way to
      ensure accurate processing reliability.

PMID- 8277445
TI  - An alternate procedure for making a remount cast for a locking type removable
      partial denture.
AB  - This procedure describes the use of silicone impression material to make an index
      that will correctly position a hinge and latch removable partial denture when a
      remount cast is being made. This procedure ensures that the partial denture can
      be retrieved with the index without stressing the retentive components of the
      partial denture and the remaining dentition. Recovering the remount cast is
      easier because the latch can be released before the impression index is separated
      from the cast.

PMID- 8277446
TI  - A speech-aid prosthesis for anterior maxillary implant-supported prostheses.
AB  - A procedure has been described that can improve speech deficiencies associated
      with anterior maxillary implant-supported prostheses. The speech-aid prosthesis
      has been found to be safe, effective, and cost-efficient.

PMID- 8277447
TI  - Protective cover cap for implant attachment.
AB  - A procedure is described for use of a cast metal cover cap to protect implant
      prosthesis attachments during finishing and polishing. The cap helps prevent
      distortion or damage to the implant.

PMID- 8277448
TI  - Attachment of wrought wire clasp to metal framework.

PMID- 8277450
TI  - How to improve light curing output.

PMID- 8277449
TI  - Line-of-vision surgical guide to implant placement in the anterior mandible.

PMID- 8277451
TI  - [Computerized evaluation of tumor volume with MRI. Applications to the
      surveillance of acoustic neurinoma].
AB  - Routine volume measurement techniques most often produce a rough approximate with
      poor accuracy for smaller structures. The results are generally improved by
      increasing the examination time, so that the technique then becomes unusable in
      daily practice. We propose a semiautomated volume calculation method with MRI,
      and its application to the surveillance of non-operated acoustic neuromas. This
      calculation technique, based on a threshold-setting method, allows accurately
      delineating the contours of the structures to be measured on each section and
      quickly calculating the total volume. After testing its reliability on control
      volumes, this techniques has been used to assess the evolutive nature of 16
      acoustic neuromas with mild symptoms in 15 patients rejected for surgery. The
      radiological examinations were 428 days apart in average. On the basis of the
      obtained results, a theoretic tumor doubling time was calculated, thus allowing
      comparison between all patients. All controlled neuromas had a theoretic doubling
      time ranging from 427 to 4,884 days, corresponding to little- or non-evolutive
      lesions, which may be explained by the series selection bias excluding evolutive
      tumors referred to surgery. Owing to its rapidity and easy use, this
      semiautomated volume calculation technique for MRI seems to be very interesting
      as it allows reliably quantifying a volume variation that is usually estimated
      approximately.

PMID- 8277452
TI  - [Lipoblastic meningioma. An uncommon benign tumor].
AB  - Often mentioned and not much documented, the lipoblastic meningioma is an unusual
      extra-axial benign tumor. It has spontaneously hypodensity in CT and appears with
      a high signal in MRI in T1-weighted sequence. Its vascularisation is rich and
      shows a strong contrast intake. Its resection is known as easy and its prognosis
      is excellent. The authors report here the observation of a 65 year old women
      having a lipoblastic meningioma. Literature is gone through and differential
      diagnoses are considered.

PMID- 8277453
TI  - [Kaposi sarcoma of the lungs in patients with acquired immunodeficiency syndrome
      (AIDS). Thoracic radiography and scanning].
AB  - Twenty-four patients with AIDS presenting with Kaposi's sarcoma of the lung were
      retrospectively studied to assess the merits of thoracic radiographs and of CT
      for the diagnosis of this disease. Evidence for Kaposi's sarcoma of the lung was
      given by a characteristic fiberendoscopic appearance in 10 cases and by the
      histologic diagnosis in 14 cases. All patients had chest radiographs and 14
      patients a concomitant thoracic CT study. Chest radiographs showed perihilar
      opacities in 18 patients, nodules in 8, mediastinal and/or hilar adenopathies in
      2 and pleural effusion in 16. Comparison of the patients who had had thoracic
      radiographs and a CT scan showed better detection of adenopathies, described in 2
      cases on chest radiographs and 7 on CT scans, and of nodules, detected in 5 cases
      on chest radiographs and 6 on CT scans. In 12 patients with perihilar opacities
      on thoracic radiographs, CT provided a better view of the peribronchovascular
      distribution of these opaque areas. In 1 patient, CT showed peribronchovascular
      thickening while radiographs were normal. In 1 patient, both examinations were
      normal. This study emphasizes the merits of thoracic radiographs and, even more,
      of CT for the diagnosis of Kaposi's sarcoma of the lung. Peribronchovascular
      thickening appears to be a characteristic sign that is well analyzed with
      computed tomography. Since histological evidence of Kaposi's sarcoma is rarely
      obtained because of the aggressive nature of biopsies in such patients, CT has an
      important role for the diagnosis of this condition.

PMID- 8277454
TI  - [Characterization of hepatic hydatid cysts of pseudotumor form. Scanner versus
      echography].
AB  - The authors report about a series of 38 patients with hepatic cysts (HHC) that
      had a pseudotumoral form on sonography (type IV in Gharbi's classification), that
      were explored both with sonography and with CT. While sonography had made the
      diagnosis of HHC possible in 4 cases out of 38 only, CT easily established this
      diagnosis in all cases. In addition, the latter technique has demonstrated the
      various tissue components accounting for the pseudotumoral sonographic image
      (hydatid sand, parietal calcifications, daughter cysts, intracystic air). It also
      allows assessing the number of sites and, better than with sonography, the signs
      of rupture of a hydatid cysts.

PMID- 8277455
TI  - [Correlations between the clinical test/MRI/arthroscopy in acute knee injuries].
AB  - Authors study retrospectively 81 cases of isolated recent (less than three
      months) knee traumas. These include clinical aspects, NMR, arthroscopy. Clinical
      examinations have been graded: 1. possible lesion; 2. likely lesions; 3.
      confirmed lesions. Clinical examinations and NMR results are compared to
      arthroscopy considered as reference. Clinical examination of acute traumatic knee
      is essential. Nevertheless, its value for detecting precise lesions is poor,
      except for knee locking well correlated with meniscal tears. Results show that
      NMR provide better results than clinical examination. NMR is reliable for
      detecting tears of posterior cruciate ligament, tears of posterior horn of
      menisci (sensibility: 93%; specificity: 80%). Its results are less effective for
      appreciation of lesion of anterior cruciate ligament (sensibility: 88%;
      specificity: 78%) because of partial tears and functional but not morphologic
      damage. It is the only method able to evidence osteochondral injuries and soft
      tissues associated lesions in traumatic knees. Emergency NMR scans show results
      no differences in results compared with routine examinations. However, one should
      keep in mind that negative NMR cannot exclude small cartilaginous lesions and
      partial tears of anterior cruciate ligament. According to these results and the
      known qualities of NMR (non invasive), we propose that this type of investigation
      should be more largely included in diagnostic attitude for acute injured knee.
      Emergency diagnostic arthroscopy could be efficiently replaced by NMR knee
      examination.

PMID- 8277456
TI  - [Value of gradient echo MRI in patellar chondromalacia].
AB  - The use of MRI in the evaluation of cartilaginous lesions is now well
      established. Thirty patients suspected of presenting such lesions were
      investigated by MRI with gradient echo sequences. Twelve patients had an
      arthroscopy either before or after the MRI. The sequences have allowed
      characterisation of the lesions of chondromalacia and have showed early lesions
      not visible at arthroscopy, without need for intraarticular contrast injection.

PMID- 8277457
TI  - [Renal Doppler ultrasonography in the diagnosis of acute obstructions of the
      upper urinary tract].
AB  - A comparative study of the resistivity indices (RI) obtained in both kidneys has
      been carried out in 30 controls and 60 patients with suspected unilateral acute
      obstruction of the upper urinary tract. Doppler findings (difference in the mean
      RI of both kidneys, delta RI) in the pathologic population have been
      systematically correlated to the data yielded by intravenous pyelography (IVP).
      In the control population delta RI was always < or = 0.03 (mean delta RI = 0.01,
      SD = 0.01). Considering that an increase in delta RI > or = 0.05 (> mean RI + 3
      SD) is significant, 93% sensitivity and 100% specificity are obtained for the
      diagnosis of unilateral acute obstruction. Comparison of the resistivity indices
      of both kidneys is more specific and more sensitive than the assessment of the
      index on the obstructed side only; it improves the performance of ultrasonography
      in the initial diagnosis of acute urinary tract obstruction.

PMID- 8277458
TI  - [The centenary of radiology in the USA].

PMID- 8277459
TI  - Antibiotic impregnated beads in open fractures. A report on the technique and
      possible applications in military surgery.
AB  - The use of antibiotic impregnated beads has been shown to be a valuable adjunct
      in the prevention of infection in open fractures. The bead pouch technique
      employs these beads within the wound, producing high local levels of antibiotic
      in a moist environment. This effectively inhibits bacterial colonisation and
      wound infection whilst preventing desiccation of structures such as bone and
      tendons. This technique can be used to manage wounds until soft tissue cover is
      obtained, whether by delayed primary suture or by plastic surgical means. The
      potential use in acute military surgery includes the management of wounds
      associated with fractures, damage to tendons or neuro-vascular injury. In such
      cases delay in soft tissue cover may be clinically necessary or dictated by
      casualty evacuation to rearward surgical facilities. The bead pouch technique
      offers a means of managing the wound between initial wound surgery and soft
      tissue cover.

PMID- 8277460
TI  - An inexpensive method of quality assessment in anastomosis workshops.
AB  - A method of comparing the quality of intestinal anastomoses performed in craft
      workshops is described. The equipment is readily available in any hospital,
      inexpensive and requires no technical construction. The apparatus accurately
      measures the intraluminal pressure at the first sign of anastomotic leak and a
      method of deriving the wall tension is explained. Calculation of wall tension at
      the point of failure allows comparison of anastomoses of different size. An
      instructor can therefore monitor the improvement of an individual trainee or rank
      a class according to the quality of their anastomoses.

PMID- 8277461
TI  - Aedes albopictus--a new disease vector for Europe?
AB  - Aedes albopictus is an important and widespread vector of dengue in many tropical
      countries. Its eggs and larvae are readily transported in commodities, such as
      old vehicle tyres, to many temperate regions, where it is able to survive and
      breed. It could thus become a serious health threat in Europe.

PMID- 8277462
TI  - Nasal polyps--a preliminary diagnosis.
AB  - It is often considered that where nasal obstruction can be attributed to the
      presence of nasal polyps that the diagnostic process is at an end. The fact that
      the majority of simple nasal polyps are benign reinforces this view. Linked with
      this, the fact that the majority of serving soldiers are healthy, may lead the
      unwary into not suspecting some of the other types of nasal polyp.

PMID- 8277463
TI  - Watson-Jones tenodesis for chronic ankle joint instability.
AB  - Twenty-three patients (22 soldiers and 1 civilian) were admitted to the Cambridge
      Military Hospital between May 1990 and May 1992 with chronic inversion
      instability of an ankle and underwent Watson-Jones Tenodesis. A retrospective
      study was carried out to evaluate their results.

PMID- 8277464
TI  - Minimum alveolar concentration of halothane: an ethnic comparison.
AB  - The minimum alveolar concentration (estimate of spread) of halothane which was
      determined in 42 Chinese, Nepalese or European patients was found to be 0.70%
      (0.66-0.74%) in Chinese and 0.70% (0.65-0.76%) in Nepalese and 0.68% (0.65-0.72%)
      in Europeans, using the Spearman Karber method of analysis. This preliminary
      trial suggests that there is no ethnic difference in the minimum alveolar
      concentration of halothane between Asians and Europeans.

PMID- 8277465
TI  - Neurological or cardiological assessment of transient altered consciousness?
AB  - Cardiac arrhythmias are a recognized cause of transient alteration of
      consciousness and unless suspected, a cardiac aetiology for apparent neurological
      symptoms may be overlooked. We retrospectively assessed the variation in the
      investigations of 122 patients who were referred to our hospital over a twelve
      month period for assessment of transient alteration of consciousness and we
      attempted to identify any factors which might have influenced the clinical
      outcome for these individuals. Eighteen patients were initially referred for
      cardiological opinion and 104 for neurological assessment. Sixty-one patients
      presented with syncope, 43 with seizures, and 18 with presyncope. A baseline
      electroencephalogram (EEG) was obtained in 104 (85%) and 65 (53%) were also
      subjected to a stress EEG. Cerebral dysrhythmia was documented in 14 patients. A
      standard electrocardiogram (ECG) was recorded in only 71 (58%) and sinus
      bradycardia (heart rate < 60/min) was observed in 34. Twenty-four hour (Holter)
      ECGs were recorded in only 58 (48%). Ventricular pauses (at least 1.84 seconds)
      and/or profound bradycardia (heart rate < 40/min) occurred during waking hours in
      10 patients and were more likely to be detected in individuals who also exhibited
      bradycardia on standard ECG (8 patients) (p < 0.05). After six months, 35 (29%)
      of the 122 patients still lacked a diagnosis and although cerebral dysrhythmia
      had been diagnosed with equal frequency in the bradycardia and non-bradycardia
      groups, 21 (62%) of those with bradycardia were still symptomatic compared with
      11 (30%) of the non-bradycardia group (p < 0.02). Our findings indicate that, at
      present, investigation of patients with transient altered consciousness lacks a
      coordinated approach and bradycardia may influence the diagnosis and morbidity of
      these individuals. We suggest that greater attention should be paid to possible
      cardiac causes of transient altered consciousness and that only under joint
      direction of a cardiologist and a neurologist can efficient and thorough
      investigation of these patients be realised.

PMID- 8277466
TI  - Childhood consultation rates in general practice--factors associated with the
      variations in attendance; a review.
AB  - General Practitioners catering for Service families need to be aware of the
      multiple influences on patients consultation. The children who attend frequently
      are those who have already been ill and those that attend a nursery school. The
      mother is influential if she has had experience in looking after children, if she
      has had employment out of the home and if her formal education was poor. The
      psychological state of the mother has been shown to have an impact and to be
      linked to the childhood consultation rate. This psychological state could well be
      influenced by frequent life events such as moving house and absence from the home
      of the spouse.

PMID- 8277467
TI  - Metachronous bilateral testicular tumours of differing histologies.
AB  - Bilateral Testicular tumours are rare. A teratoma followed by a seminoma is one
      of the most uncommon forms of presentation. A case is described in a 29 year old
      soldier with a review of the literature and a discussion of the problems
      associated with diagnosis.

PMID- 8277468
TI  - Rheumatic fever: atypical presentation in an adult.
AB  - A 38 year old Caucasian lady presented with a history of vague ill health, raised
      ESR and prolonged P-R interval on ECG. These features became normal within a
      week. Contrary to the usual presentation, this patient developed fleeting
      arthritis, one of the major diagnostic features of rheumatic fever, towards the
      end of her illness. It is important to recognise such variants of rheumatic
      fever, even in retrospect, for the sake of giving penicillin prophylaxis to
      prevent cardiac morbidity.

PMID- 8277469
TI  - Late presentation of portal vein thrombosis as a complication of appendicitis.
AB  - A case of appendicitis which resulted in portal pyaemia, hepatic and splenic
      abscesses, presumed portal vein thrombosis and subsequent portal hypertension is
      described. It confirms the merit of ultrasonic imaging in monitoring abscess
      resolution but questions the ability of the technique to recognise acute
      suppurative portal endophlebitis.

PMID- 8277470
TI  - Pre-peritoneal prosthetic repair of recurrent inguinal herniae.

PMID- 8277471
TI  - Necrotising fasciitis of the leg after ischio-rectal abscess.

PMID- 8277472
TI  - Communicable disease control.

PMID- 8277473
TI  - The use of acetic acid for Pseudomonas infection.

PMID- 8277474
TI  - 12 year review of testicular tumour treatment by the army medical services.
AB  - Between 1977 and 1988 144 patients with tumours of testicular origin were
      referred to the Queen Elizabeth Military Hospital at Woolwich. 140 of these were
      malignant and all but two were treated and followed. Three of the malignant
      lesions appeared to be extragonadal. During the 12 year period staging has become
      increasingly accurate and treatment protocols have improved. These changes are
      reflected in this series. Ten deaths from tumour occurred (6.9%) but only one of
      these in the last three years of the study period despite an increasing case load
      at the time. The clinical presentation, treatment, and results of treatment are
      presented and the advances of treatment and improvement of prognosis discussed.

PMID- 8277475
TI  - Assessment of the effects of atmospheric oil pollution in post war Kuwait.
AB  - A prospective study was undertaken to assess and monitor the effects of oil
      pollution in soldiers exposed in Kuwait in 1991 after Op Granby. One hundred and
      twenty five soldiers were monitored over a five month period by measurement of
      Forced Expiratory Volume (in one second) (FEV1) and Forced Vital Capacity (FVC).
      Although no demonstrable changes were observed, this study has gone some way to
      filling the gap in research in this environmentally sensitive field.

PMID- 8277476
TI  - Pressure effects from the military stretcher.
AB  - Attention is drawn to a possible deficiency in the folding pole canvas stretcher.
      Canvas tensioning and uniformity of support in the variety of stretcher where the
      canvas is attached by screws and metal strips was noted to be defective. High
      interface pressures were found on this type of stretcher, a problem not
      encountered in stretchers where the canvas tensioning is with regularly spaced
      tacks. Patients supported on the screw and strip variety may be at a higher risk
      of pressure necrosis.

PMID- 8277477
TI  - Ovarian response in World Health Organization group II anovulatory women during
      consecutive human menopausal gonadotropin cycles.
AB  - While ovulation induction with human menopausal gonadotropins (hMG) is commonly
      used to treat refractory ovulatory disorders, little is known about the
      characteristics of multiple consecutive treatment cycles. Since such cycles may
      be required to achieve pregnancy, it is important to ensure that the ovarian
      response is not compromised during consecutive cycles. We examined the ovarian
      response and cycle characteristics of 25 women with World Health Organization
      (WHO) group II ovulatory disorders who underwent three consecutive ovulatory hMG
      cycles. The total hMG dose and duration of treatment increased significantly
      between the first and third consecutive hMG cycles, although the final estradiol
      levels remained similar. While the mean numbers of follicles > or = 14 mm in
      diameter were comparable, the size of the largest follicle was significantly
      greater during the third cycle as compared to the first. These results suggest
      that while the ovary required more vigorous stimulation during subsequent cycles,
      the ultimate hormonal and follicular response did not appear to be compromised
      during this series of three consecutive cycles.

PMID- 8277478
TI  - Treatment of post-cesarean section endometritis with ampicillin and sulbactam or
      clindamycin and gentamicin.
AB  - Seventy-seven patients were prospectively enrolled in a randomized clinical trial
      to compare two antimicrobial regimens for the treatment of post-cesarean section
      endometritis. The two groups were not significantly different with respect to
      age, race, gravidity, parity, hours in labor, cesarean section indication,
      preoperative or postoperative hemoglobin/hematocrit, pretreatment white blood
      cell count or pretreatment temperature. Pretreatment urine, blood and endometrial
      cultures were obtained. One or more organisms was recovered from the endometrium
      in 90% of the patients using a double-lumen sampling device. The most frequent
      endometrial isolates were Peptostreptococcus and Bacteroides species, followed by
      Gardnerella vaginalis and enterococci. Thirty (81%) of 37 patients receiving
      ampicillin/sulbactam and 33 (83%) of 40 receiving gentamicin and clindamycin
      responded to therapy. There were 14 (18%) treatment failures, 7 in each group.
      Five (36%) of the 14 clinical failures were due to septic pelvic
      thrombophlebitis, 2 (14%) of the 14 failures were complications of intraabdominal
      abscesses, and the remaining 7 patients responded after a change in their
      antibiotic regimen. We conclude that ampicillin/sulbactam and
      clindamycin/gentamicin are similarly effective for the treatment of post-cesarean
      section endometritis.

PMID- 8277479
TI  - Laparoscopic management of ectopic pregnancy.
AB  - In response to the dramatic increase in the incidence of ectopic pregnancy in the
      United States and worldwide, diagnostic and surgical procedures have evolved to
      provide safe, efficacious and cost-effective resolutions of this condition.
      Laparoscopic management of ectopic pregnancy, developed in this regard, continues
      to be the subject of equivocal reviews. In an effort to further elucidate the
      issues surrounding the laparoscopic management of ectopic pregnancy, a
      retrospective investigation was undertaken of 82 women admitted to a community
      hospital in the Northwest for operative resolution of ectopic pregnancy. Of these
      patients, 81 (99%) were treated successfully by the laparoscopic approach, the
      majority (90%) by salpingostomy, with no occurrence of postoperative
      complications. In contrast to the 3-14% incidence of persistent ectopic pregnancy
      found in other studies of this approach, a 1% rate was noted here. A sampling of
      patients treated by laparoscopic and non-laparoscopic approaches demonstrated a
      13% reduction in hospital charges for those treated by laparoscopy. In addition,
      laparoscopy involved a shorter hospital stay and fewer of the unpleasant effects
      associated with abdominal surgery. The results of this study further support
      laparoscopic management as an efficacious, safe and cost-effective approach for
      the resolution of ectopic pregnancy.

PMID- 8277480
TI  - Amniotic fluid index. Gestational age-specific values for normal human pregnancy.
AB  - Amniotic fluid volume is an important parameter in the assessment of fetal well
      being. The purpose of this study was to define the values of the amniotic fluid
      index for normal pregnancy by week of gestation in our population. The amniotic
      fluid index was measured prospectively in 892 patients with a normal singleton
      pregnancy between 15 and 40 weeks and an estimated fetal weight between the 10th
      and 90th percentile. The results were stratified by week of gestation. From a
      median of 10.3 cm (range, 8.7-13.7, 5th-95th percentile) at 15 weeks' gestation,
      the amniotic fluid index rose progressively to a maximum median of 14.0 cm
      (range, 4.0-18.6) at 30 weeks. The index then gradually declined to a median of
      9.1 cm (range, 4.8-14.2) by 40 weeks' gestation. The difference between the
      median index for preterm patients (11.9 cm) and that for the term group (10.8 cm)
      was found to be statistically significant (P < .05). The difference between the
      median amniotic fluid index for the total group and the medians for the preterm
      and term patients was also significant (P < .05). Gestational age-specific values
      of amniotic fluid index should be used, and the 5th and 95th percentiles serve as
      the lower and upper limits, respectively, of normal.

PMID- 8277481
TI  - Plasma androgens and sex hormone binding globulin in women with polycystic
      ovaries diagnosed by transvaginal ultrasound.
AB  - In order to investigate the androgen and sex hormone binding globulin (SHBG)
      levels in the polycystic ovary, we compared the total testosterone, free
      testosterone and SHBG levels in three patterns of polycystic ovary diagnosed with
      transvaginal ultrasonography (18 in group 1, fewer than 5 cysts identified; 16 in
      group 2, 5-10 cysts; and 27 in group 3, 10 or more). Free testosterone, but not
      total testosterone, significantly correlated with body mass index. Androgen
      levels were found to increase and SHBG levels to decrease with increases in the
      amount of ovarian cysts, and the evaluation of free testosterone was important in
      diagnosing the polycystic ovary syndrome.

PMID- 8277482
TI  - Premenstrual syndrome and related hormonal changes. Long-acting gonadotropin
      releasing hormone agonist treatment.
AB  - The results of long-acting, injectible gonadotropin releasing hormone agonist
      (GnRH-a) and placebo treatment of severe premenstrual syndrome (PMS) patients
      with regular menstrual cycles and without known psychiatric disorders are
      reported. Diagnosis was made according to the Menstrual Symptom Questionnaire and
      Menstrual Symptom Diary scores. In a placebo-controlled, crossover study, 12
      subjects were given either normal saline or depot leuprolide acetate (7.5 mg)
      every 30 days, starting with the onset of menses. Each subject received the same
      agent twice before switching to the other and did not known which agent was
      given. A significant decrease in PMS symptoms was reported by all subjects in
      both treatment regimens. Biweekly venous blood sampling showed significant
      elevations of beta-endorphin levels and suppression of gonadotropin
      concentrations in subjects receiving depot leuprolide treatment. Short-term
      treatment of severe PMS with an injectible, long-acting GnRH-a may not treat the
      disease more than do saline injections in a group of women selected by certain
      criteria.

PMID- 8277483
TI  - Senior obstetric-gynecologic residents' perceptions of their surgical training,
      experiences and skill.
AB  - Senior obstetric and gynecologic residents' self-perceptions of surgical skill
      seem to be unrelated to the kinds of didactic experiences received or to the
      number of basic gynecologic procedures performed during training. These data
      offer further support for the need for a comprehensive reevaluation of the
      components of gynecologic surgical curricula; the cognitive, behavioral and
      psychomotor educational objectives of such training; and the methods by which the
      outcomes for these objectives are measured.

PMID- 8277484
TI  - A new wave guide for use with a CO2 delivery system for laparoscopic surgery.
AB  - This study assessed the performance of the Heraeus LaserSonics InfraGuide with
      the 250Z CO2 laser in 46 patients undergoing laparoscopic surgery. Procedures
      included vaporization of endometriosis, adhesiolysis, ovarian cystectomy,
      uterosacral ligament transection, salpingoplasty, fimbrioplasty,
      neosalpingostomy, ectopic linear salpingostomy and myomectomy. The InfraGuide
      system was effective in transmitting laser energy to the pelvis. Advantages and
      disadvantages of the accessory sheath, spot diameter, HeNe aiming beam and
      optical laser coupler are discussed. The InfraGuide offers the surgeon an
      additional useful laparoscopic instrument.

PMID- 8277485
TI  - Vaginal delivery of breech-vertex twins.
AB  - The safety of vaginal birth for breech-vertex twins has not been addressed
      directly before. We retrospectively compared the perinatal outcome of two groups
      of breech-vertex twins: 24 delivered vaginally and 35 delivered abdominally.
      Vaginal delivery was allowed under the same protocol developed for singletons in
      breech presentation. Both groups had similar maternal and neonatal
      characteristics except for a significantly higher rate (P = .003) of pregnancies
      after infertility in the abdominal delivery group. Intergroup differences in
      perinatal outcome, as measured by Apgar scores and morbidity and mortality cases,
      were not significant. Our data suggest that if measures for safe vaginal delivery
      are taken, this route appears to incur no morbidity and mortality for breech
      vertex twins.

PMID- 8277486
TI  - Recurrent stillbirth. Significance and characteristics.
AB  - We sought to identify the significance of recurrent stillbirth and to determine
      the contributory etiologic factors for this phenomenon. Data were analyzed and
      retrospective chart review conducted for all stillbirths occurring during a 13
      year period. Subjects were divided into two groups: those for whom the current
      stillbirth was the first and those who had had a previous stillbirth. The study
      included 48,479 consecutive multiparous women, of whom 403 had delivered
      stillborn infants (8.31/1,000 live births). For 34 of these subjects, this
      represented a recurrent stillbirth (84.36/1,000 live births). The recurrent
      stillbirth group had a 10.15-fold higher risk for stillbirth. Additionally, this
      group had a twofold higher incidence of diabetes and hypertensive disease than
      did those women experiencing their first stillbirths; furthermore, the
      gestational age and birth weight of the stillborn infants were significantly
      lower in the recurrent-stillbirth group (P < .0004 and < .007, respectively).
      Such factors as socioeconomic class, chorioamnionitis and erythroblastosis
      fetalis, traditionally cited as contributing to repeated fetal loss, were not
      significant. Although recurrent stillbirth remains an unsolved problem, improving
      health care to specific groups within high-risk populations may reduce fetal
      loss.

PMID- 8277487
TI  - Acute amniotic fluid loss and changes in the amniotic fluid index. Correlation
      and effect on umbilical artery velocimetry.
AB  - This study was undertaken to determine whether changes in the amniotic fluid
      index accurately reflected measured amniotic fluid loss after artificial rupture
      of membranes and whether this acute loss of fluid volume affected umbilical
      artery resistance as measured by Doppler velocimetry. Twenty-five uncomplicated
      term pregnancies underwent umbilical artery velocimetry and amniotic fluid index
      determination in the active phase of labor before and after amniotomy. Amniotic
      fluid loss was measured by direct collection of fluid during and immediately
      following rupture of the membranes. The preamniotomy and postamniotomy data were
      compared using the paired t test, and the relationship between amniotic fluid
      index change and actual fluid loss was tested by linear regression. The change in
      the amniotic fluid index after amniotomy was significant (paired t test, P <
      .0001), and a significant relationship was found by linear regression between the
      actual amniotic fluid loss and the change in the amniotic fluid index (P < .01,
      r2 = .28). Despite significant changes in the amniotic fluid index, however, no
      significant change in the umbilical artery systolic/diastolic ratio could be
      demonstrated. Our data suggest that amniotomy in the active phase of labor in
      uncomplicated pregnancies does not affect umbilical artery resistance and that
      the amniotic fluid index is a limited, semiquantitative method of assessing acute
      changes in amniotic fluid volume.

PMID- 8277488
TI  - Neurofibromatosis and pregnancy. An update.
AB  - Neurofibromatosis is one of the most frequent genetic diseases in humans.
      Pregnancy in neurofibromatosis patients is, however, less common. Most current
      information on pregnancy and neurofibromatosis is derived from case reports,
      which may not reflect the true situation. In the past 15 years only two series of
      pregnant neurofibromatosis patients were reported in the English-language
      literature. We present our experience with 34 pregnancies in nine
      neurofibromatosis patients who delivered at our medical center. While fertility
      does not seem to be impaired in neurofibromatosis, these patients experience a
      higher-than-expected rate of first-trimester spontaneous abortions (20.7%),
      stillbirths (8.7%) and intrauterine growth retardation (13.0%). A high rate of
      cesarean section (26%) was also observed in our series. We conclude that pregnant
      neurofibromatosis patients constitute a high-risk group, in danger of developing
      life-threatening complications. However, with proper antenatal care, most
      pregnant neurofibromatosis patients can deliver safety if the pregnancy continues
      beyond the first trimester.

PMID- 8277489
TI  - Thyrotoxicosis complicated by ectopic pregnancy. First reported case.
AB  - The reported incidence of thyrotoxicosis during pregnancy ranges from 0.02% to
      3.7%, with an average of 0.2%. Ectopic pregnancy occurs in 1 of 66 pregnancies in
      the United States. The signs and symptoms of thyrotoxicosis complicate the
      diagnosis and surgical management of an ectopic pregnancy. This is the first
      reported case of thyrotoxicosis complicated by an ectopic pregnancy. The patient
      presented with a surgical abdomen (in this case an ectopic pregnancy) coupled
      with thyrotoxicosis. The combination of prompt presurgical medical intervention
      and operative correction prevented the mortality associated with a ruptured tubal
      pregnancy and thyroid storm.

PMID- 8277490
TI  - Laparoscopic removal of ovarian lesions. A report of two cases.
AB  - Removing dermoid cysts laparoscopically can be time-consuming and tedious, and
      adhesions may develop after surgery. We describe the use of an endoscopic pouch
      to remove apparently benign ovarian cysts in two cases. This method permits
      removal of ovarian lesions with little or no risk of intraperitoneal spillage. We
      believe that its use in laparoscopic removal of tumors or cysts is a reasonable
      alternative to more traditional approaches and should be considered if
      laparoscopic treatment is planned.

PMID- 8277491
TI  - Colovaginal fistula secondary to diverticular disease. A report of two cases.
AB  - Two cases of diverticular abscess presented with abdominal pain, pelvic mass and
      vaginal discharge. Both patients had previously undergone hysterectomy. Although
      relatively rare, colovaginal fistula secondary to diverticular disease should be
      considered in the differential diagnosis in an elderly woman with similar
      symptoms.

PMID- 8277492
TI  - Massive ovarian tumor complicating pregnancy. A case report.
AB  - Adnexal masses complicate approximately 1/2,000 pregnancies. Teratomas are the
      most common ovarian neoplasms found in pregnancy, representing up to 36% of
      adnexal masses. However, almost all these dermoids are less than 10 cm in
      diameter. We present a case of a massive benign cystic teratoma complicating
      pregnancy. The patient initially presented with what appeared to be ascites.
      Imaging evaluation included ultrasound, magnetic resonance and angiography. These
      studies demonstrated a large teratoma. The tumor was resected without
      complications. Important aspects of perioperative care are discussed.

PMID- 8277493
TI  - Sonographic diagnosis of bladder perforation by an intrauterine device. A case
      report.
AB  - Perforation of the urinary bladder by an intrauterine device (IUD) is extremely
      rare. In this report we present a case of ultrasound diagnosis of perforation of
      the bladder by a Copper-T IUD.

PMID- 8277494
TI  - Reduced calcitriol requirements for treating hypoparathyroidism during lactation.
      A case report.
AB  - We reduced the dose of calcitriol from 0.75 to 0.25 microgram/d to maintain low
      normal serum calcium levels in a hypoparathyroid woman during lactation.
      Calcitriol requirements quickly returned to 0.75 microgram/d when she
      discontinued breast-feeding. In her previous pregnancy, failure to reduce the
      dose of calcitriol resulted in serious hypercalcemia 11 days after she began
      breast-feeding. The changing requirement for calcitriol in our patient related
      directly to the falling level of estradiol. Although the cause or causes of
      diminished calcitriol requirements in hypoparathyroid women during lactation
      remains unclear, increased bone resorption promoted by low plasma estrogen levels
      may be an important mechanism. We conclude that the dose of calcitriol should be
      reduced during lactation and that both the hypoparathyroid mother and her infant
      should be carefully monitored to detect abnormal serum calcium levels.

PMID- 8277495
TI  - Synthesis and antimicrobial evaluation of a series of 7-[3-amino (or aminomethyl)
      4-aryl (or cyclopropyl)-1-pyrrolidinyl]-4-quinolone- and -1,8-naphthyridone-3
      carboxylic acids.
AB  - A series of 6-fluoroquinolone- and 6-fluoro-1,8-naphthyridone-3-carboxylic acids
      possessing a [3-amino (or aminomethyl)-4-aryl (or cyclopropyl)-1-pyrrolidinyl]
      group at C-7 were synthesized and evaluated for their antimicrobial activity. The
      effect of the relative stereochemistry of the pyrrolidinyl substituents, as well
      as the presence of different functional groups on the 4-aryl (or cyclopropyl)
      moiety, was investigated in conjunction with their attachment to several
      quinolone or naphthyridone nuclei. In general, the incorporation of substituents
      on the aryl (or cyclopropyl) ring decreased in vitro and in vivo activity,
      regardless of the nature and relative position of the substituent. Bulky,
      lipophilic groups and substitution at the 2- and 3-position of the aromatic ring
      were particularly deleterious. Within a limited subset of derivatives, cis
      substitution of the pyrrolidine ring was less favorable than trans substitution.
      The majority of these effects were more apparent against the Enterobacteriaceae
      than against any other Gram-negative or Gram-positive organism and could be
      associated with negative interactions related to permeability or transport
      factors.

PMID- 8277496
TI  - Three-dimensional QSAR of human immunodeficiency virus (I) protease inhibitors.
      1. A CoMFA study employing experimentally-determined alignment rules.
AB  - Comparative molecular field analysis (CoMFA), a three-dimensional, quantitative
      structure-activity relationship (QSAR) paradigm, was used to examine the
      correlations between the calculated physicochemical properties and the in vitro
      activities of a series of human immunodeficiency virus (HIV-1) protease
      inhibitors. The training set consisted of 59 molecules from five structurally
      diverse transition-state isostere classes: hydroxyethylamine, statine,
      norstatine, keto amide, and dihydroxyethylene. The availability of X-ray
      crystallographic data for at least one representative from each class bound to
      the protease provided information regarding not only the active conformation of
      each ligand but also, via superimposition of protease backbones, the relative
      positions of each ligand with respect to one another in the active site of the
      enzyme. Once aligned, these molecules served as templates on which additional
      congeners were field-fit minimized. Additional alignment rules were derived from
      minimizations of the ligands in the active site of the semirigid protease. The
      predictive ability of each resultant model was evaluated using a test set
      comprised of molecules containing a novel transition-state isostere:
      hydroxyethylurea. Crystallographic studies (Getman, D.P.; et al. J. Med. Chem.
      1993, 36, 288-291) indicated an unexpected binding mode for this series of
      compounds which precluded the use of the field-fit minimization alignment
      technique. The test set molecules were, therefore, subjected to a limited
      systematic search in conjunction with active-site minimization. The conformer of
      each molecule expressing the lowest interaction energy with the active site was
      included in the test set. Field-fit minimization of neutral molecules to crystal
      ligands and active-site minimizations of protonated ligands yielded predictive
      correlations for HIV-1 protease inhibitors. The use of crystallographic data in
      the determination of alignment rules and field-fit minimization as a molecular
      alignment tool in the absence of direct experimental data regarding binding modes
      is strongly supported by these results.

PMID- 8277497
TI  - Studies on analogues of classical antifolates bearing the naphthoyl group in
      place of benzoyl in the side chain.
AB  - Analogues of classical antifolates with the 4-aminobenzoyl group replaced by 4
      amino-1-naphthoyl were synthesized for study after molecular modeling indicated
      ample spatial accommodation for the naphthalene ring and even larger groups in
      models based on reported X-ray crystallographic data describing the binding of
      methotrexate to human dihydrofolate reductase (DHFR). The side-chain precursors,
      N-(4-amino- and 4-(methylamino)-1-naphthoyl)-L-glutamic acid diethyl esters, were
      synthesized, and the 2,4-diamino-substituted heterocyclic groups were attached
      using several methods. Target compounds included naphthoyl analogues of
      aminopterin (AMT), methotrexate (MTX), 5-deazaAMT, 5-deazaMTX, 5-methyl-5
      deazaAMT, 5-methyl-5-deazaMTX, and 5,8-dideazaAMT. A 5,6,7,8-tetrahydronaphthoyl
      analogue of 5-deazaAMT was also prepared. None of the naphthoyl analogues showed
      loss in binding to DHFR compared with the corresponding antifolate bearing the
      benzoyl group, thus confirming the anticipated bulk tolerance. Only the 5,6,7,8
      tetrahydronaphthoyl analogue displayed reduced antifolate effects. Substrate
      activity toward folylpolyglutamate synthetase was, however, severely compromised.
      The naphthoyl compounds were transported into L1210 cells 3-6 times more readily
      than MTX, and despite apparently low levels of intracellular polyglutamylation,
      each compound was found to be significantly more potent than MTX in inhibiting
      tumor cell growth in vitro in three lines (L1210, HL60, and S180). The MTX, 5
      methyl-5-deazaAMT, and 5-methyl-5-deazaMTX analogues were evaluated in vivo
      alongside MTX against E0771 mammary adenocarcinoma in mice. All three proved more
      effective than MTX in retarding the tumor growth. The naphthoyl analogue of 5
      deazaAMT strongly inhibited DHFR from Pneumocystis carinii, Toxoplasma gondii,
      and rat liver giving IC50 (pM) values of 0.53, 2.1, and 1.6 respectively, but
      this compound did not inhibit in vitro growth of T. gondii, thus indicating lack
      of transport.

PMID- 8277498
TI  - CC-1065 functional analogues possessing different electron-withdrawing
      substituents and leaving groups: synthesis, kinetics, and sequence specificity of
      reaction with DNA and biological evaluation.
AB  - Antitumor agent CC-1065 functional analogues possessing different electron
      withdrawing substituents and leaving groups have been synthesized. The extent and
      the relative rates of DNA cleavage following alkylation by these CPI structures
      and thermal treatment were determined independently by an ethidium binding assay
      and by agarose gel electrophoresis experiments. The anticipated preferential
      covalent binding to adenine sites within the minor groove was confirmed by
      sequencing determination of selected agents on high-resolution gels. Certain of
      the synthetic agents, unlike CC-1065, also bind covalently to G sites with weaker
      intensity. The cytotoxicities of these compounds were also determined against KB
      cells in vitro. Compounds bearing a bromo or nitro group in the benzene ring and
      a methylsulfonyl as a leaving group are 10 and 5 times more potent than their
      unsubstituted counterparts, respectively. Compounds bearing a methylsulfonyl as a
      leaving group are more potent than those bearing a chlorine.

PMID- 8277499
TI  - Nucleosides and nucleotides. 122. 2'-C-cyano-2'-deoxy-1-beta-D
      arabinofuranosylcytosine and its derivatives. A new class of nucleoside with a
      broad antitumor spectrum.
AB  - Design, synthesis, and tumor cell growth inhibitory effects of 2'-C-cyano-2'
      deoxy-1-beta-D-arabinofuranosyl derivatives of cytosine (1i, CNDAC), thymine
      (6a), uracil (6c), and adenine (6d) have been described. The synthesis of the
      target compounds was achieved from the corresponding 2'-keto nucleosides 2a-d.
      Cyanohydrins of 2a-d were converted to thionocarbonates, which were deoxygenated
      to give the desired 2'-beta-cyano-2'-deoxy derivatives 5a-d, followed by
      deprotection to furnish the target nucleosides. Of these nucleosides, CNDAC was
      the most potent inhibitor of cell growth with an IC50 value of 0.53 microM
      against L1210 cells. In vitro cytotoxicity of CNDAC against human tumor cell
      lines was also examined; compared with that of 1-beta-D-arabinofuranosylcytosine
      (ara-C) and 5-fluorouracil (5-FU), CNDAC was more cytotoxic to several cell lines
      refractory to ara-C. The in vivo effect of CNDAC on M5076 mouse reticulum cell
      sarcoma was very strong; 99% tumor volume inhibition on day 20 was achieved when
      it was administrated orally on days 1, 4, 7, 10, 13, and 16 at a dose of 400
      mg/kg/day, while 5'-deoxy-5-fluorouridine (5'-DFUR) and 5-FU caused only 50%
      inhibition at a dose of 500 mg/kg/day and 28% inhibition at a dose of 50
      mg/kg/day, respectively, on the same schedule. These results indicated that CNDAC
      may have potential as a new antineoplastic agent with a broad antitumor spectrum.

PMID- 8277500
TI  - Nucleosides and nucleotides. 123. Synthesis of 1-(2-deoxy-2-isocyano-beta-D
      arabinofuranosyl)cytosine and related nucleosides as potential antitumor agents.
AB  - 2'-Deoxy-2'-isocyano-1-beta-D-arabinofuranosylcytosine (8, NCDAC) has been
      synthesized as a potential antitumor antimetabolite from a corresponding 2'-azido
      2'-deoxy-1-beta-D-arabinofuranosyluracil derivative 2a. Uracil and thymine
      analogues 6a and 6b of 8 were also prepared. Attempts to synthesize 2'-deoxy-2'
      isocyanocytidine (14b) failed due to the insertion of the 2'-alpha isocyano group
      into the 3'-OH group, affording the 2',3'-oxazoline derivative 15b. Stability of
      the isocyano derivative 6a and 2',3'-oxazoline derivative 15a under basic and
      acidic conditions were examined. The isocyano group in 6a was stable in basic
      conditions but unstable even in weakly acidic conditions to furnish the
      corresponding 2'-beta formamide derivative 17. Compound 15a was easily hydrolyzed
      the corresponding 2'-alpha formamide derivative 16 on treatment with H2O at room
      temperature. The cytotoxicity of 8, 6a, and 6b was examined in mouse and human
      tumor cells in vitro and compared with that of ara-C. Of these nucleosides, 8 was
      moderately cytotoxic to these cell lines. In vivo antitumor activity of 8 against
      Lewis lung carcinoma cells was also investigated and 8 showed only moderate tumor
      volume inhibition.

PMID- 8277501
TI  - Synthesis and cytotoxicity of potential tumor-inhibitory analogues of trimelamol
      (2,4,6-tris[(hydroxymethyl)methylamino]-1,3,5-triazine) having electron
      withdrawing groups in place of methyl.
AB  - In exploring the structural features which determine the antitumor activity of
      2,4,6-tris-[(hydroxymethyl)methylamino]-1,3,5-triazine (trimelamol, 1), we have
      synthesized analogues in which the methyl groups have been replaced by the
      electron-withdrawing substituents 2,2,2-trifluoroethyl (5), propargyl (13), and
      cyanomethyl (15) via the respective tris(alkylamino)triazines 3, 12, and 14.
      Three mono[(hydroxymethyl)amino]triazines (4, 7, and 10) were also prepared. All
      the new tris(hydroxymethyl) derivatives showed cytotoxicities toward a variety of
      experimental rodent and human ovarian tumor cell lines similar to those shown by
      1, the cyanomethyl analogue (15) having the most favorable profile.
      Mono(hydroxymethyl) derivatives (4 and 7) were ca. one-third as toxic. The new
      tris(hydroxymethyl) analogues were more stable to aqueous hydrolysis than was 1.
      Half-life (pH 7.5) values were, for 1, 120 min, for 5, 690 min, for 13, 450 min,
      and for 15, 275 min, but at pH 2.0, 15 (t1/2 350 min) was the most stable. This
      cyanomethyl analogue was also the most water-soluble, being comparable to 1
      whereas 5 and 13 were poorly soluble.

PMID- 8277502
TI  - Brush-border-enzyme-mediated intestine-specific drug delivery. Amino acid
      prodrugs of 5-aminosalicylic acid.
AB  - 5-Aminosalicylic acid (5-ASA) is the active principle of a number of preparations
      aimed at the treatment of inflammatory bowel diseases, such as Crohn's disease
      and ulcerative colitis, but its efficacy is limited by early absorption and
      metabolism. The possibility to exploit the selective hydrolytic activity of brush
      border enzymes such as aminopeptidase A and carboxypeptidases was studied by
      preparing the following four amino acid prodrugs of 5-ASA: 5-(N-L-aspartylamino)
      2-salicylic acid, disodium salt (18), 5-(N-L-glutamylamino)-2-salicylic acid,
      disodium salt (19), [(5-aminosalicyl)-L-prolyl]-L-leucine, sodium salt (25), and
      [[5-(N-L-glutamylamino)salicyl]-L-prolyl]-L-leucine, disodium salt (28). In these
      compounds, the peptide bond is selectively split by the intestinal brush border
      aminopeptidase A (compounds 18, 19, and 28) and carboxypeptidases (compounds 25
      and 28).

PMID- 8277503
TI  - Isocyanines and pseudoisocyanines as a novel class of potent noradrenaline
      transport inhibitors: synthesis, detection, and biological activity.
AB  - Noradrenaline, the neurotransmitter of the sympathetic nervous system, is removed
      from the extracellular space by both neuronal and extraneuronal transport
      mechanisms. In the past, further investigation of the extraneuronal type of
      noradrenaline transporter was severely hampered by the lack of potent inhibitors.
      Here, we describe the synthesis of various novel noradrenaline transport
      inhibitors which belong to the chemical class of isocyanine and pseudoisocyanine
      dyes. The biological activity of these compounds was investigated in a tissue
      culture system (Caki-1 cells). 1,1'-Diisopropyl-2,4'-cyanine, 1,1'-diethyl-2,2'
      cyanine, and 1-ethyl-1'-isopropyl-2,2'-cyanine turned out as the most potent
      inhibitors of the extraneuronal noradrenaline transport known so far. At 100
      nmol/L, these compounds diminished extraneuronal noradrenaline transport by about
      95%. Their IC50's were below 20 nmol/L. In addition, a rapid and sensitive method
      (based on HPLC with fluorometric detection) to measure these compounds in body
      fluids is reported.

PMID- 8277504
TI  - Synthesis and pharmacological activity of a series of dihydro-1H-pyrrolo[1,2
      a]imidazole-2,5(3H,6H)-diones, a novel class of potent cognition enhancers.
AB  - A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones were
      synthesized. These bicylic derivatives contain both the 2-pyrrolidinone and 4
      imidazolidinone nuclei, already recognized as important for cognition enhancing
      activity. In addition, these structures maintain the backbone of piracetam and
      oxiracetam with the acetamide side chain restricted in a folded conformation.
      Their ability to reverse scopolamine-induced amnesia was assessed in a one trial,
      step-through, passive avoidance paradigm. The main features observed are a potent
      antiamnestic activity after ip administration (minimal effective dose being
      between 0.3 and 1 mg/kg ip for most compounds), the presence of a bell-shaped
      dose-response curve and, generally, a reduction of biological activity after po
      administration. However, the unsubstituted compound (15, dimiracetam) shows no
      evidence of a bell-shaped dose-response curve and completely retains activity
      when given orally, being 10-30 times more potent than the reference drug
      oxiracetam.

PMID- 8277505
TI  - Non-peptide angiotensin II receptor antagonists. 1. Design, synthesis, and
      biological activity of N-substituted indoles and dihydroindoles.
AB  - A series of N-acylated indoles (12-18), N-alkylated indoles (19-24), N-acylated
      dihydroindoles (26-30), and N-alkylated dihydroindoles (31-34) were synthesized
      and evaluated in the in vitro AT1 (rabbit aorta) and AT2 (rat midbrain) binding
      assay. The carboxylic acid 3-[[N-(2-carboxy-3,6-dichlorobenzoyl)-5
      indolyl]methyl]-5,7-dimeth yl- 2-ethyl-3H-imidazo[4,5-b]pyridine (14b) was found
      to be the most potent AT1 (IC50 = 0.8 nM) antagonist in the N-acylated indole
      series and displayed a 25-fold higher potency than the parent unsubstituted
      derivative 14a (AT1 IC50 = 20 nM) and a 22-fold greater potency than the
      corresponding dihydroindole analog 27 (AT1 IC50 = 18 nM). Replacement of the
      terminal carboxyl (COOH) of 14a with the bioisostere tetrazole in 16 (AT1 IC50 =
      5 nM, AT2 IC50 = 130 nM) not only improved the AT1 potency by 4-fold but also
      resulted in a 50-fold increase in AT2 activity. In the N-alkylated indole series,
      the tetrazole 3-[[N-(2-tetrazol-5-yl-6-chlorobenzyl)-5- indolyl]methyl]-5,7
      dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridine (24) exhibited the highest AT1 (IC50 =
      1 nM) activity, revealing a 230-fold increase in AT1 activity as a result of the
      incorporation of the isosteric tetrazole for the carboxyl (COOH) of 20 and a
      nearly 9-fold increase over the corresponding deschloro analog 22 (AT1 IC50 = 8.7
      nM). Tetrazole 34 was identified as the most potent (AT1 IC50 = 18 nM) AT1
      receptor antagonist in a structurally distinct series of compounds derived from N
      alkylation of dihydroindole 25. A new class of highly potent (14b, AT1 IC50 = 0.8
      nM; 24, AT1 IC50 = 1 nM) AT1-selective non-peptide AII receptor antagonists
      derived from N-substituted indoles and dihydroindoles is disclosed. Tetrazole 24
      of the N-alkylated indole series displayed good in vivo activity by blocking the
      AII-induced pressor response for 5.5 h after intravenous administration in
      conscious normotensive rats at a 1.0 mg/kg dose level.

PMID- 8277506
TI  - Non-peptide angiotensin II receptor antagonists. 2. Design, synthesis, and
      biological activity of N-substituted (phenylamino)phenylacetic acids and acyl
      sulfonamides.
AB  - The design, synthesis, and biological activity of a new class of highly potent
      non-peptide AII receptor antagonists derived from N-substituted
      (phenylamino)phenylacetic acids and acyl sulfonamides which exhibit a high
      selectivity for the AT1 receptor are described. A series of N-substituted
      (phenylamino)phenylacetic acids (9) and acyl sulfonamides (16) and a tetrazole
      derivative (19) were synthesized and evaluated in the in vitro AT1 (rabbit aorta)
      and AT2 (rat midbrain) binding assay. The (phenylamino)phenylacetic acids 9c (AT1
      IC50 = 4 nM, AT2 IC50 = 0.74 microM), 9d (AT1 IC50 = 5.3 nM, AT2 IC50 = 0.49
      microM), and 9e (AT1 IC50 = 5.3 nM, AT2 IC50 = 0.56 microM) were found to be the
      most potent AT1-selective AII antagonists in the acid series. Incorporation of
      various substituents in the central and bottom phenyl rings led to a decrease in
      the AT1 and AT2 binding affinity of the resulting compounds. Replacement of the
      carboxylic acid (CO2H) in 9c, 9d, and 9e with the bioisostere acyl sulfonamide
      (CONHSO2Ph) resulted in a (5-7)-fold increase in the AT1 potency of 16a (AT1 IC50
      = 0.9 nM, AT2 IC50 = 0.2 microM), 16b (AT1 IC50 = 1 nM, AT2 IC50 = 2.9 microM),
      and 16c (AT1 IC50 = 0.8 nM, AT2 IC50 = 0.42 microM) and yielded acyl sulfonamides
      with subnanomolar AT1 activity. Incorporation of the acyl sulfonamide (CONHSO2Ph)
      for the CO2H of 9c not only enhanced the AT1 potency but also effected a marked
      increase in the AT2 potency of 16a (AT2 IC50 = 0.74 microM of 9c vs 0.2 microM of
      16a) and made it the most potent AT2 antagonist in this study. Replacement of the
      CO2H of 9b with the bioisostere tetrazole resulted in 19 (AT1 IC50 = 15 nM) with
      a 2-fold loss in the AT1 and a complete loss in the AT2 binding affinity.
      (Phenylamino)phenylacetic acid 9c demonstrated good oral activity in AII-infused
      conscious normotensive rats at an oral dose of 1.0 mg/kg by inhibiting the
      pressor response for > 6 h. Acyl sulfonamides 16a-c displayed excellent in vivo
      activity by blocking the AII-induced pressor response for > 6 h after oral
      administration in conscious rats at a 3.0 mg/kg dose level. Both acyl
      sulfonamides 16a and 16c exhibited superior in vivo activity in rats compared to
      that of (phenylamino)phenylacetic acid 9c.

PMID- 8277507
TI  - Phenylselenenyl- and phenylthio-substituted pyrimidines as inhibitors of
      dihydrouracil dehydrogenase and uridine phosphorylase.
AB  - Lithiation of 5-bromo-2,4-bis(benzyloxy)pyrimidine (3) with n-BuLi at -80 degrees
      C followed by the addition of diphenyl diselenide or diphenyl disulfide as an
      electrophile furnished the corresponding 5-(phenylhetera)-2,4
      bis(benzyloxy)pyrimidine, which on exposure to trimethylsilyl iodide in CH2-Cl2
      at room temperature yielded the 5-(phenylhetera)uracils in 70-75% yield.
      Similarly, the 6-(phenylhetera)uracils were prepared from 6-bromo-2,4
      bis(benzyloxy)pyrimidine (10). 1-[(2-Hydroxyethoxy)methyl]-5
      (phenylselenenyl)uracil (PSAU, 18) and 1-(ethoxymethyl)-5-(phenylselenenyl)uracil
      (17) were synthesized by the electrophilic addition of benzeneselenenyl chloride
      to the acyclic uracils under basic conditions. These compounds were evaluated for
      their ability to inhibit dihydrouracil dehydrogenase (DHUDase, E.C. 1.3.1.2),
      orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.2.10), uridine phosphorylase
      (UrdPase, E.C. 2.4.2.3), and thymidine phosphorylase (dThdPase, E.C. 2.4.2.4). 5
      (Phenylselenenyl)uracil (PSU, 6) and 5-(phenylthio)uracil (PTU, 7) inhibited
      DHUDase with apparent K(i) values of 4.8 and 5.4 microM, respectively. The
      corresponding 6-analogues, compounds 13 and 14, demonstrated inhibitory activity
      against OPRTase. PTU as well as PSU and its riboside, 2'-deoxyriboside, and
      acyclonucleosides were inhibitors of UrdPase, with PSAU (18) being the most
      potent with an apparent K(i) value of 3.8 microM. None of the compounds evaluated
      had any effect on dThdPase. Interestingly, most of the compounds showed modest
      selective anti-human-immunodeficiency-virus activity in acutely infected primary
      human lymphocytes.

PMID- 8277508
TI  - 2- and 4-fluorinated 16 alpha(-)[125I]iodoestradiol derivatives: synthesis and
      effect on estrogen receptor binding and receptor-mediated target tissue uptake.
AB  - The effect of 2- and 4-fluoro substitution on the estrogen receptor-mediated
      tissue localization of radioiodinated 16 alpha-iodoestradiol (16 alpha-IE2) and
      its 11 beta-methoxy analogue (11 beta-OMe-16 alpha-IE2) was evaluated.
      Electrophilic substitution of estrone or 11 beta-methoxyestrone with N
      fluoropyridinium salt gave the 2- and 4-fluoro derivatives which were
      subsequently converted to the 3,17 beta-enol diacetate and brominated to yield
      exclusively the 16 alpha-bromo analogues. Epimerization gave the corresponding 16
      beta-bromoestrones which were reduced to the 17 beta-hydroxy derivatives. Halogen
      exchange with NaI or Na[125I]I provided the A-ring fluorinated 16 alpha
      iodoestradiols. The 4-F analogue exhibited higher affinity for estrogen receptors
      than the corresponding 2-F analogue, and these differences were more pronounced
      at higher incubation temperatures. Biodistribution studies in immature female
      rats showed that 4-fluoro substitution had only a moderate effect on receptor
      mediated tissue uptake of the parent molecules whereas 2-fluoro substitution
      resulted in strongly diminished tissue specificity. The lower target selectivity
      of the 2-F, compared to the 4-F, analogue correlates to some extent with their
      different receptor binding properties; however, the rate of catabolism may also
      be involved. Differences in blood clearance further accentuated the localization
      properties to yield particularly high uterus to blood ratios in the case of the 4
      F-11 beta-OMe-16 alpha-IE2, suggesting the potential of the analog labeled with
      123I as a radiopharmaceutical for receptor imaging in nuclear medicine. The
      isopotential maps of the fluorinated steroids, obtained via semiempirical
      computer modeling on the molecular structures, show striking differences between
      the 4-F and 2-F derivatives reflecting their varying biological properties.

PMID- 8277509
TI  - Structure-activity relationships of the antimalarial agent artemisinin. 1.
      Synthesis and comparative molecular field analysis of C-9 analogs of artemisinin
      and 10-deoxoartemisinin.
AB  - A series of C-9 beta-substituted artemisinin analogs (2-21) were synthesized via
      dianion alkylation of the total synthetic intermediate 57 followed by subsequent
      ozonolysis/acidification, or by alkylation of the enolate derived from (+)-9
      desmethylartemisinin, 2. Inactive acyclic analogs 22 and 23 were synthesized by
      nucleophilic epoxide opening and the ring contracted analog 24 was prepared by an
      alternate route. 10-Deoxo-9-alkyl derivatives 68 and 70 were synthesized
      convergently from intermediates in the preparation of 9-alkyl derivatives. In
      vitro bioassay was conducted in W-2 and D-6 clones of drug resistant Plasmodium
      falciparum. Comparative molecular field analysis (CoMFA) of the 9-alkyl lactone
      derivatives provided a model with a cross-validated r2 = 0.793. Inclusion of
      inactive 1-deoxyartemisinin analogs 26-42 provided a model with a value of 0.857.
      The activities of a number of other analogs of divergent structure (43-56) were
      predicted with good accuracy using the CoMFA model.

PMID- 8277510
TI  - Development of 1,4-benzodiazepine cholecystokinin type B antagonists.
AB  - A series of 3-(arylureido)-5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists
      of the peptide hormone cholecystokinin (CCK), are described. Derived by reasoned
      modification of the CCK-A selective 3-carboxamido-1,4-benzodiazepine, MK-329,
      this paper chronicles the development of potent, orally effective compounds in
      which selectivity for the CCK-B receptor subtype was achieved. The principal lead
      structure that emerged from these studied is L-365,260, a compound which has been
      submitted for clinical evaluation. Details of the ability to modulate the
      receptor interactions of these benzodiazepines by appropriate structure
      modifications are discussed which imply the possibility of further refining the
      CCK-B receptor affinity and selectivity of this class of compounds.

PMID- 8277511
TI  - Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides.
AB  - An extensive study of the requirements for effective binding of N-carboxyalkyl
      peptides to human stromelysin, collagenase, and to a lesser extent, gelatinase A
      has been investigated. These efforts afforded inhibitors generally in the 100-400
      nM range for these matrix metalloproteinases. The most significant increase in
      potency was obtained with the introduction of a beta-phenylethyl group at the P1'
      position, suggesting a small hydrophobic channel into the S1' subsite of
      stromelysin. One particular compound, N-[1(R)-carboxyethyl]-alpha(S)-(2
      phenylethyl)glycyl-L-leucine,N- phenylamide (79a), is relatively selective for
      rabbit stromelysin with a K(i) = 6.5 nM and may prove useful for elucidating the
      role of endogenously-produced stromelysin in lapine models of tissue degradation.

PMID- 8277512
TI  - Studies of the synthesis, immunology, and cytotoxicity of a cyclic octapeptide
      corresponding to TNF-alpha-(59-66).
AB  - In an attempt to investigate possible binding domains of the tumor necrosis
      factors (TNF), we have previously synthesized a cyclic hexapeptide corresponding
      to murine TNF-(127-132) (cTNF-1). In this report, we describe the synthesis and
      biological activity of another cyclic octapeptide corresponding to human TNF
      alpha-(59-66) (cTNF-2). The design of these cyclic peptides is based on their
      high sequence homology with corresponding fragments of human TNF-alpha or TNF
      beta. Similar to cTNF-1, the cyclic octapeptide cTNF-2 displayed low in vitro
      cytotoxicity against human HeLa and HEP-2 cell lines. The cyclic peptides cTNF-2
      and cTNF-1 were then tested for the induction of interleukin-1 (IL-1) production
      from human peripheral blood mononuclear cells and monocytes in vitro. At low
      concentrations, the IL-1 levels induced by these cyclic peptides were similar to
      that of recombinant TNF-alpha. However, the IL-1 production by cTNF-2 stimulation
      was dose-dependently increased and reached that of a lipopolysaccharide (LPS; 0.1
      micrograms/mL) level. These findings suggest that the fragments corresponding to
      human TNF-alpha-(59-66) and murine TNF-(127-132) may represent certain binding
      domains of the tumor necrosis factors that elicit IL-1 production.

PMID- 8277513
TI  - Synthesis and optical resolution of (R)- and (S)-trans-7-Hydroxy-2-[N-propyl-N
      (3'-iodo-2'-propenyl)amino]tetralin: a new D3 dopamine receptor ligand.
AB  - An improved method for synthesis and resolution of (R,S)-trans-7-hydroxy-2-[N
      propyl-N-(3'-iodo-2'-propenyl)amino]tetralin (trans-7-OH-PlPAT,5), a new D3
      dopamine receptor ligand, was reported. Both isomers, (R)-(+)- and (S)-(-)-5,
      were prepared and characterized. HPLC retention times obtained on a chiral column
      for these isomers were consistent with those observed for [125I]-(R)-(+)- and (S)
      (-)-5. Direct radioiodination of an optically resolved tin precursor, (R)-(+)-7,
      yielded the desired [125I](R)-(+)-5, which is a simpler method for synthesis of
      this ligand. Binding studies with membrane preparations containing D3 dopamine
      receptors expressed in Spodoptera frugiperda (Sf9) cells also suggested that the
      [125I](R)-(+)-5 is the active isomer (Kd = 0.05 nM). The schemes described may
      provide an efficient way for synthesizing a large quantity of this new D3
      dopamine receptor ligand for in vivo behavior studies.

PMID- 8277514
TI  - 6-Azasteroids: potent dual inhibitors of human type 1 and 2 steroid 5 alpha
      reductase.

PMID- 8277515
TI  - Program and abstracts of the 10th GRRC meeting. Beaune, France, 6-7 April 1993.

PMID- 8277516
TI  - The Bhopal accident and methyl isocyanate toxicity.
AB  - The Bhopal accident, the world's worst industrial disaster, in which nearly 40
      metric tons of methyl isocyanate (MIC) was released from the Union Carbide
      pesticide plant, occurred nearly 10 yr ago during the night of December 2 and 3,
      1984. Over 3000 people residing in areas adjacent to the plant died of pulmonary
      edema within 3 d of the accident. Follow-up studies revealed pulmonary,
      ophthalmic, reproductive, immunologic, neurological, and hematologic toxicity
      among the survivors. Despite high reactivity, MIC can traverse cell membranes and
      reach distant organs, perhaps as a reversible conjugate with glutathione, which
      may explain some of the systemic effects of MIC. MIC can be degraded as a result
      of pyrolysis and interaction with water, but none of the breakdown products can
      duplicate the toxicity observed in Bhopal and in animal models. MIC may be the
      most toxic of all isocyanates because of its very high vapor pressure relative to
      other isocyanates and because of its ability to exert toxic effects on numerous
      organ systems.

PMID- 8277517
TI  - Cadmium-109 metabolism in mice. IV. Diet versus maternal stores as a source of
      cadmium transfer to mouse fetuses and pups during gestation and lactation.
AB  - The transfer of 109Cd from dam to offspring during gestation and lactation was
      studied in uniparous mice. From 70 to 210 d of age and during the subsequent
      reproductive period, young adult female mice received drinking water containing
      tracer amounts of 109Cd (8 ppb total Cd) and nutrient-sufficient or -deficient
      solid diet containing stable Cd (5 ppm Cd). The nutrient quality of the deficient
      diet was patterned after that consumed by Japanese women who contracted itai-itai
      disease. To evaluate established maternal stores as a potential source of cadmium
      transfer to pups, some dams were switched to water with no 109Cd and diet with an
      environmental or control level of cadmium (0.25 ppm Cd) during the reproductive
      period. The resulting pups were analyzed for 109Cd at birth and at 7-d intervals
      throughout the lactation period. Pup 109Cd content at birth, representative of
      the amount transferred via the placenta during gestation, accounted for less than
      1% of the total 109Cd transferred during the full reproductive period. During
      lactation, 109Cd levels in pups from dams with current 109Cd exposure
      approximately tripled with each 7-d interval; no significant differences occurred
      due to nutrient quality of the dams' diet. For 21-d-old pups, 98% of the 109Cd
      burden came from the diet of the dam, while only 2% came from her tissue stores,
      primarily the hepatic one. Such fractions represented a transfer per pup of about
      0.01% of the oral 109Cd dose ingested by the dam during the reproductive period
      and about 0.05% of the 109Cd in her tissue stores. Overall, transfer per litter
      amounted to about 7% of the dietary 109Cd dose absorbed and retained by the dam
      during that interval and about 0.2% of the 109Cd from tissue stores. On lactation
      d 21, 90% of the total 109Cd in pups was sequestered in the gastrointestinal
      tract. Cadmium transfer was additionally examined in multiparous mice that began
      a repetitive breeding program at 70 d of age at the time of introduction to the
      same diet/water regimens already described. Overall, females consuming nutrient
      sufficient diet experienced 5 consecutive 42-d rounds of gestation/lactation,
      while their deficient diet counterparts experienced 3 nonconsecutive rounds
      during an equivalent period. Transfer was examined during their last
      gestation/lactation experience. Throughout the lactation interval, 109Cd transfer
      to pups was about 30% increased for multiparous versus uniparous females;
      however, transfer again was not significantly affected by nutrient quality of the
      dams' diet.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8277518
TI  - Loss of cathepsin B activity in alveolar macrophages after in vitro quartz
      phagocytosis.
AB  - Bovine alveolar macrophages were incubated up to 20 h with DQ12 quartz particles,
      either in untreated native form or pretreated with dipalmitoyl lecithin. The
      content of cathepsin B and N-acetylglucosaminidase was measured in the culture
      supernatant and in the cells. After incubation, a loss of about 50% of the total
      cathepsin B activity in the culture dish was observed, whereas no influence on
      total N-acetylglucosaminidase content occurred. Loss of cathepsin B activity was
      completely prevented by the pretreatment of quartz with the surfactant component
      dipalmitoyl lecithin. Similarly, a complete abrogation of the quartz effect on
      cathepsin B was noted when the cells were incubated with quartz in the presence
      of NH4Cl in order to prevent phagosome-lysosome fusion. There was also no
      influence on cathepsin B activity when a lysosome-rich fraction, prepared from
      alveolar macrophages, was incubated together with quartz. It was concluded that
      the reduction of cathepsin B activity was related with the intralysosomal
      deposition of quartz particles.

PMID- 8277519
TI  - Designing a biological monitoring program to assess community exposure to
      chromium: conclusions of an expert panel.
AB  - The possible benefits of biological monitoring of large groups of people
      potentially exposed to environmental contaminants has become an area of much
      interest in recent years. Because chromite-ore processing residue has been found
      in some soils in northern New Jersey, urinary chromium monitoring of people in
      the community was evaluated as a potentially useful tool. In an attempt to
      identify those who could be exposed and to quantify the magnitude of exposure to
      the chromium in these soils, the New Jersey Department of Health (NJDOH)
      initiated a public health screening project. In 1992, the NJDOH proposed to
      evaluate over 4000 people who lived or worked near these sites. Volunteers were
      administered a questionnaire and were given a limited physical examination, and a
      single spot urine sample was collected. Because of the difficulties in using
      urinary chromium to assess low-level exposure and the potential implications of
      any regulatory decisions that could be based on the results of this project, a
      panel of experts was convened to evaluate the protocol. The panel consisted of
      five scientists and physicians with expertise in toxicology, dermatology,
      epidemiology, biological monitoring, and analytical chemistry. Like a World
      Health Organization group, the panel concluded that although urine biomonitoring
      can be useful in evaluating high levels of exposure to chromium, it is not
      reliable for assessing low-level exposure similar to that which may have occurred
      in northern New Jersey. The panel also noted that when urinary biomonitoring is
      to be used to assess the public's possible exposure, a large number of
      precautions must be taken to ensure the accuracy and usefulness of the results.
      The single most important recommendation was to collect a second, and perhaps a
      third, spot urine (or 24-h urine) sample before concluding that a person may be
      routinely overexposed. These suggestions are applicable to designing a
      biomonitoring program for nearly any environmental contaminant to which a
      community may be exposed. A review of scientific literature associated with
      biological monitoring of chromium is provided.

PMID- 8277520
TI  - Using human sweat to extract chromium from chromite ore processing residue:
      applications to setting health-based cleanup levels.
AB  - Chromite ore processing residue (COPR) containing measurable levels of hexavalent
      and trivalent chromium. [Cr(VI) and Cr(III), respectively] has been used to fill
      in low-lying areas in Hudson County, N.J. While it has been demonstrated that
      direct dermal contact with solutions containing Cr(VI) may elicit allergic
      contact dermatitis (ACD) in previously sensitized individuals, it is unknown to
      what degree skin moisture may solubilize Cr(VI) from COPR adhering to skin. An
      accurate estimate of this extraction potential is necessary to establish COPR
      concentrations of Cr(VI) and Cr(III) that are protective of eliciting ACD in
      sensitized individuals. The purpose of this study was to measure the extractable
      fraction of Cr(VI) and total chromium [Cr(III) and Cr(VI)] in soils impacted by
      COPR using human sweat as the extractant. Human sweat was collected from seven
      male volunteers. Samples of COPR material containing the following Cr(VI) and
      total chromium concentrations were collected: Cr(VI), 16, 136, and 1240 ppm;
      total chromium, 932 and 6660 ppm. The samples were sieved to obtain a uniform
      particle size < 500 microns. The samples were then mixed with human sweat at 30
      degrees C for 12 h, after which the sweat was filtered and analyzed to determine
      the dissolved concentration of Cr(VI) and total chromium. The data from these
      analyses show that no detectable levels (limit of detection = 0.010 ppm) of
      Cr(VI) were leached from COPR containing 16 ppm Cr(VI). At Cr(VI) concentrations
      of 136 and 1240 ppm, less than 0.1% of the Cr(VI) present in the COPR sample was
      extracted into sweat, and sweat concentrations were 0.133 ppm Cr(VI) or less.
      Similarly, the amount of Crtotal extracted was 0.3% or less at COPR
      concentrations as high as 6600 ppm Crtotal, and sweat concentrations were 2.3 ppm
      Crtotal or less. If a minimum concentration of 10 ppm (Bagdon and Hazen, 1991) to
      54 ppm (Paustenbach et al., 1992) Cr(VI) in sweat is required to elicit an ACD
      response in chromium-sensitive individuals, the current study results suggest
      that a COPR Cr(VI) concentration of at least 10,000-54,000 ppm would be required
      to elicit ACD. If 500 ppm (or greater) of solubilized Cr(III) is required to
      elicit an ACD response (NJDEPE, 1992a), then a COPR concentration of 250,000 ppm
      Cr(III) or greater would be required to elicit an allergic response. These
      results suggest that ACD is unlikely to occur as a result of environmental
      exposure to the COPR.

PMID- 8277521
TI  - Percutaneous uptake, distribution, and excretion of pyrene in rats.
AB  - Groups of 12 male Wistar rats, of about 400 g body weight, were dosed with 2, 6,
      or 15 mg/kg of 14C-labeled pyrene, dissolved in acetone, applied to 4 cm2 of a
      shaved area of the mid back. Three animals in each dose group were killed at 1,
      2, 4, and 6 d post-dosing, and their principal organs were removed and analyzed
      for pyrene and [14C]pyrene equivalents. Urine and feces, as well as the area of
      skin to which the dose was applied, were also analyzed for [14C]pyrene
      equivalents. The rate of uptake from the skin was rapid (t1/2 0.5-0.8 d) relative
      to rate processes for the other organs, and about 50% of the applied dose was
      excreted over the 6 d of the study. The significant decrease in the fraction of
      the dose excreted and in the normalized amounts distributed to the various organs
      and tissues, as the dose increased for all chemical species measured, was
      strongly suggestive of nonlinear kinetics, as has been observed in previous
      studies. Levels of pyrene were highest in the liver, kidneys, and fat. Levels of
      metabolites were also high in the lung. It was evident that the dermal route of
      uptake was not insignificant for this model polycyclic aromatic hydrocarbon and
      may represent a significant exposure route for exposed humans.

PMID- 8277523
TI  - Tobacco-specific N-nitrosamines and Areca-derived N-nitrosamines: chemistry,
      biochemistry, carcinogenicity, and relevance to humans.
AB  - Nicotine and the minor tobacco alkaloids give rise to tobacco-specific N
      nitrosamines (TSNA) during tobacco processing and during smoking. Chemical
      analytical studies led to the identification of seven TSNA in smokeless tobacco
      (< or = 25 micrograms/g) and in mainstream smoke of cigarettes (1.3 micrograms
      TSNA/cigarette). Indoor air polluted by tobacco smoke may contain up to 24 pg/L
      of TSNA. In mice, rats, and hamsters, three TSNA, N'-nitrosonornicotine (NNN), 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-1
      (3-pyridyl)-1-butanol (NNAL), are powerful carcinogens; two TSNA are moderately
      active as carcinogens; and two TSNA appear not to be carcinogenic. The TSNA are
      procarcinogens, agents that require metabolic activation. The active forms of the
      carcinogenic TSNA react with cellular components, including DNA, and with
      hemoglobin (Hb). The Hb adducts in chewers and smokers serve as biomarkers for
      the uptake and metabolic activation of carcinogenic TSNA and the urinary
      excretion of NNAL as free alcohol and as glucuronide for the uptake of TSNA. The
      review presents evidence that strongly supports the concept that TSNA contribute
      to the increased risk for cancer of the upper digestive tract in tobacco chewers
      and for the increased risk of lung cancer, especially pulmonary adenocarcinoma,
      in smokers. The high incidence of cancer of the upper digestive tract especially
      among men on the Indian subcontinent has been causally associated with chewing of
      betel quid mixed with tobacco. In addition to the TSNA, the betel quid chewers
      are exposed to four N-nitrosamines that are formed during chewing from the Areca
      alkaloids, two of these N-nitrosamines are carcinogens. The article also reviews
      approaches toward the reduction of the carcinogenic potency of smokeless tobacco,
      betel quid-tobacco mixtures, and cigarette smoke. Although the safest way to
      reduce the risk for tobacco-related cancers is to refrain from chewing and
      smoking, modifications of smokeless tobacco and of cigarettes are indicated to
      lead to less toxic products. Another more recent approach for reducing the
      carcinogenic effect of tobacco products is the application of chemopreventive
      agents, primarily of micronutrients. Future aspects in tobacco carcinogenesis,
      especially as it relates to TSNA, are expected in the field of molecular
      biochemistry and in biomarker studies, with the goal of identifying those tobacco
      and betel quid chewers and tobacco smokers who are at especially high risk for
      cancer.

PMID- 8277522
TI  - Risk assessment of the allergic dermatitis potential of environmental exposure to
      hexavalent chromium.
AB  - Although hexavalent chromium, Cr(VI), is a potent sensitizer and inducer of
      allergic contact dermatitis and is found in many common materials, no standard or
      guideline currently exists for protection against these effects in environmental
      exposure. There appears to be a generalized allergenic potential among the
      various compounds of Cr(VI). Estimates of the prevalence of Cr sensitivity in the
      population are uncertain, but range from about 2% of the total population in
      Finland to as high as 20% in U.S. populations with a dermatitis. Based on the
      thresholds reported for nine separate patch-test studies and statistical analysis
      of the aggregate dose-response relationship from 72 separate observations from
      these studies and on studies of allergic responses to bleaches and detergents,
      the effective threshold for elicitation of allergic contact dermatitis in
      sensitized populations is about 10 ppm (mg/L) Cr(VI) (as chromium) in solution.
      Based on evaluation of the literature on cement dermatitis, the threshold
      concentration of extractable Cr(VI) in solid material may be as low as 10 ppm
      (microgram/g). For ingestion of Cr(VI), the lowest observed effect level (LOEL)
      dose for elicitation is 0.26 microgram/kg. In calculating the threshold
      concentration of Cr(VI) in soil for elicitation of contact dermatitis,
      extractability must be taken into account.

PMID- 8277524
TI  - Effects of nitrogen dioxide on respiratory tract clearance in the ferret.
AB  - During growth and development, young children are periodically exposed to
      relatively high concentrations of various air contaminants, including tobacco
      smoke and environmental pollutants generated by fossil fuel use. The effects of
      these exposures on respiratory function and lung development are difficult to
      determine because of interindividual variation and lack of accurate dosimetry. To
      provide information on the effects of chronic exposure to a common indoor and
      outdoor pollutant during lung development, a study was performed to assess the
      effects of exposure to two concentrations of nitrogen dioxide (NO2; 0.5 or 10
      ppm) on tracer particle clearance from the airways of ferrets exposed during
      postnatal respiratory tract development. Separate groups of ferrets were exposed
      nose-only to the test atmospheres or clean air 4 h/d, 5 d/wk, for either 8 or 15
      wk. Those animals exposed for 8 wk were subsequently housed in a filtered air
      environment until the particle clearance measurements commenced at 3 wk prior to
      the end of the 15-wk exposure protocol. Radiolabeled (51Cr) tracer particles were
      deposited in the respiratory tract of all animals by inhalation, and the
      clearance rates from the head and thoracic regions were separately monitored for
      18 d. No significant effects of the NO2 exposure on head airways clearance were
      seen. In contrast, the rates of particle clearance from the thorax of both the 8-
      and 15-wk groups exposed to 10 ppm NO2 were significantly reduced, and did not
      differ from each other. Thoracic clearance was also reduced in animals exposed to
      0.5 ppm, but the rate was not significantly different from that of the clean air
      exposed controls. These results show that NO2 at moderate concentrations caused
      highly significant changes in the deep lung of the juvenile ferret, and suggest
      that impairment of the clearance function may be only slowly recovered after
      chronic exposure.

PMID- 8277525
TI  - Blood cholinesterase in rats fed an insect resistance apple clone containing a
      natural cholinesterase inhibitor.
AB  - A crab apple clone (Malus brevipes 1021), highly resistant to the apple maggot,
      is being used in breeding programs developing commercial apple cultivars. This
      study has discovered that this crab apple contains a natural cholinesterase (ChE)
      inhibitor that caused a 17.5% in vitro inhibition of rat blood ChE activity. This
      crab apple also showed a relatively high total (titratable) acidity of 1.28%. The
      commercial, nonresistant, apple cultivar McIntosh was capable of causing a 7.9%
      inhibition of blood ChE in vitro. The total acidity in McIntosh was 0.45%. A 4-wk
      feeding study compared 2 groups of 5-wk-old Fischer 344 male rats fed diets
      containing 45% of either M. brevipes or McIntosh freeze-dried apples to a third
      (control) group of rats fed a semipurified diet. In vivo blood ChE activities
      were similar in all groups of rats, as well as hemoglobin, hematocrit, and red
      blood cell counts. The liver mixed-function oxidase activity through aminopyrine
      N-demethylase in the rats fed the apple diets was higher than the controls, but p
      nitroanisole O-demethylase activity was induced only in the animals fed the
      maggot-resistant crab apple. Lowered growth with concomitant lowered food intake,
      in the otherwise healthy rats fed the maggot-resistant crab apple diet, was
      attributed to the less palatable, highly acidic fruit. This study indicates that
      the natural ChE inhibitor in the insect-resistant apple M. brevipes is apparently
      detoxified upon ingestion.

PMID- 8277526
TI  - Chemical characterization and disposition studies with 1,2,7,8
      tetrabromodibenzofuran in the rat.
AB  - Polybrominated dibenzo-p-dioxins and dibenzofurans have been identified as
      potential environmental contaminants. The present studies were designed to
      characterize the chemical disposition of a tetrabrominated dibenzofuran. The
      isomer-specific pattern of 1,2,7,8-tetrabromodibenzofuran (TBDF) was chemically
      characterized using high-pressure liquid chromatography, gas chromatography/mass
      spectrometry, infrared absorption, and proton nuclear magnetic resonance
      techniques. The absorption, distribution, and elimination of 1,2,7,8-[4,6-3H]
      TBDF were examined in the rat following a single oral, dermal, or intravenous
      dose of 1 nmol/kg. The 1,2,7,8-TBDF was rapidly excreted in the bile
      (approximately 50% of the dose in 8 h). Likewise, over half of the administered
      dose was found in the feces and intestine contents 24 h after iv administration
      and in feces 72 h after oral administration. Thus, the half-life of 1,2,7,8-TBDF
      is approximately 1 d. Major tissue depots included the liver, adipose tissue, and
      skin. The decline in hepatic concentrations observed in the iv and bile studies
      occurred in conjunction with metabolic elimination as well as a slight
      accumulation in adipose tissue. Dermal absorption of 1,2,7,8-TBDF, quantified as
      the amount contained in tissues (excluding the skin site) and excreta at 72 h,
      was estimated to be 29% of the administered dose. Thus, the general disposition
      profile of 1,2,7,8-TBDF in the rat is similar to that of other polyhalogenated
      aromatic hydrocarbons. Due to its rapid elimination, which is consistent with its
      predicted susceptibility to metabolic elimination, acute exposure to 1,2,7,8-TBDF
      would not be expected to result in the degree of toxicity associated with other
      more persistent congeners.

PMID- 8277527
TI  - Animal model for the study of methanol toxicity: comparison of folate-reduced rat
      responses with published monkey data.
AB  - We attempted to develop a rodent model that exhibits characteristics of human
      methanol toxicities such as acidosis and visual dysfunction, which are correlated
      with an accumulation of formate, a toxic metabolite of methanol. Initially three
      groups of Long-Evans rats with different levels of liver folate were prepared and
      examined for formate accumulation after methanol administration (3.5 g/kg). The
      folate-reduced (FR) rats prepared by feeding a folate-deficient diet with 1%
      succinylsulfathiazole yielded blood formate levels equivalent to those found in
      methanol-intoxicated humans and developed signs of the visual system toxicity (a
      manuscript on the latter aspect is in preparation). Responses of FR rats to a
      variety of methanol exposure scenarios were then investigated, and the results
      were compared with those reported in the literature for monkeys. Formate
      accumulation and/or lethality were used as toxic parameters for this comparative
      evaluation. In FR rats dosed orally with 3 g/kg, the blood formate concentration
      was 9.2 mmol/L at 24 h postadministration and increased to 15.6 mmol/L at 48 h.
      The same dose given to monkeys yielded a plateau of 7.4 mmol/L at 12 h after
      methanol administration, and stayed at this level for an additional 12 h. The
      area under the concentration vs. time curve for blood formate in FR rats was 2.5
      fold greater than that in monkeys when 2.0 g/kg methanol was administered. After
      a 6-h exposure to 1200 ppm and 2000 ppm methanol, the blood formate
      concentrations in FR rats were increased by 370% and 636% above the endogenous
      level, respectively. However, blood formate did not accumulate above the
      endogenous level when monkeys were exposed to methanol up to 2000 ppm for 6 h.
      Under acute inhalation exposure conditions, FR rats exposed to 3000 ppm methanol,
      20 h/d, could not survive more than 4 d. On the other hand, monkeys exposed to
      3000 ppm, 21 h/d, out-lived 20 d. Moreover, monkeys survived for more than 4 d
      even after an exposure to 10,000 ppm. Thus, these results indicate that FR rats
      are more sensitive to methanol challenges than monkeys, and suggest that the FR
      rat could be a congruous animal model for evaluating the health effects of
      methanol in humans.

PMID- 8277528
TI  - Musculoskeletal changes in children prenatally exposed to polychlorinated
      biphenyls and related compounds (Yu-Cheng children).
AB  - Fifty-five Yu-Cheng (oil-disease) children born between 1978 and 1985 to mothers
      who ate PCB-contaminated rice oil in 1978-1979 were studied and compared to age-
      and sex-matched control subjects in 1991. The children's growth profiles, bone
      mineral density and soft tissue composition, joint laxity, and serum parathyroid
      hormone, vitamin D, calcium, alkaline phosphatase, and phosphate were compared.
      The Yu-Cheng children were 3.1 cm (p < .05) smaller and had less total lean mass
      and soft tissue mass as compared to the matched control subjects. All other
      parameters studied were similar in both groups. The shorter height and decreased
      total lean mass and soft tissue content were only seen in the Yu-Cheng children
      who were the first born after the ingestion, but not in subsequent children. This
      was most likely due to decreased body burdens of the PCBs and related
      contaminants over time in the mothers.

PMID- 8277529
TI  - Morphology of popliteal lymph node responses in Brown-Norway rats.
AB  - The popliteal lymph node (PLN) assay has been proposed as a tool to predict in
      rodents those xenobiotics likely to induce autoimmune reactions in humans. To
      further validate this assay and to study the mechanisms involved, histologic
      changes in PLNs from rats injected with streptozotocin, diphenylhydantoin, pure
      acetone, or 50% ethanol were compared to a local graft-versus-host (GvH)
      reaction. This study suggests that routine histology of PLNs is instrumental to
      discard primary irritants. In addition, the hypothesis of a GvH-like mechanism in
      positive PLN responses is supported by the finding that the reference compounds
      streptozotocin and diphenylhydantoin produced histologic changes similar to a
      "true" local GvH reaction.

PMID- 8277530
TI  - A piece of my mind. Home visit.

PMID- 8277531
TI  - New NIH director faces filling top posts, focus on intramural research.

PMID- 8277532
TI  - More choices in treating AIDS-related pneumonia.

PMID- 8277533
TI  - Coordinated effort to fight breast cancer begins.

PMID- 8277534
TI  - From the Food and Drug Administration.

PMID- 8277535
TI  - From the Health Care Financing Administration.

PMID- 8277536
TI  - From the Centers for Disease Control and Prevention. Improper infection-control
      practices during employee vaccination programs--1993.

PMID- 8277537
TI  - From the Centers for Disease Control and Prevention. Multistate outbreak of viral
      gastroenteritis related to consumption of oysters--1993.

PMID- 8277538
TI  - From the Centers for Disease Control and Prevention. Update: influenza activity-
      United States and Europe, 1993-94 season.

PMID- 8277539
TI  - From the Centers for Disease Control and Prevention. Flood-related mortality-
      Missouri, 1993.

PMID- 8277540
TI  - Breast cancer screening for elderly women.

PMID- 8277541
TI  - DEA physician registration numbers: a need to know.

PMID- 8277542
TI  - Membranoproliferative glomerulonephritis associated with hepatitis C infection
      with no evidence of liver disease.

PMID- 8277543
TI  - Reducing the risk of AIDS in high school students: lifelong monogamy is the moral
      solution.

PMID- 8277544
TI  - Why isn't a commercial sex worker a prostitute?

PMID- 8277545
TI  - Factors influencing bone lead concentration in a suburban community assessed by
      noninvasive K x-ray fluorescence.
AB  - OBJECTIVE: To determine the influence of demographic, exposure and medical
      factors on the bone lead concentration of subjects with background
      (nonindustrial) environmental lead exposure. DESIGN: Survey. SETTING: Suburban
      residential community. PARTICIPANTS: A total of 101 subjects (49 males, 52
      females; aged 11 to 78 years) were recruited from 49 of 123 households
      geographically located in a suburban residential neighborhood unexposed to any
      major source of industrial lead emissions. MAIN OUTCOME MEASUREMENTS: Cortical
      bone lead concentrations in the midshaft of the tibia were noninvasively measured
      by in vivo K x-ray fluorescence. Blood lead concentrations were measured by
      anodic stripping voltammetry. An administered questionnaire assessed potential
      sources of lead exposure and medical conditions affecting bone metabolism.
      RESULTS: After the exclusion of one outlier, log-transformed bone lead
      concentration was highly correlated with age (r = .71; P < or = .0001). Bone lead
      concentration showed no significant change up to age 20 years, increased with the
      same slope in men and women between ages 20 and 55 years, and then increased at a
      faster rate in men older than 55 years. In addition to the variables age and sex,
      the best fitting multiple regression model for bone lead concentration (R2 = .66;
      P < or = .0001) revealed a positive correlation with total pack-years of
      cigarette smoking and a negative correlation with a history of having nursed an
      infant for longer than 2 weeks. Blood lead concentrations of the subjects were
      low (geometric mean, 0.24 mumol/L [4.9 micrograms/dL]) and after log
      transformation were weakly correlated with log-transformed bone lead
      concentration (r = .23; P = .02). CONCLUSIONS: The age- and sex-related increases
      in bone lead concentration found by K x-ray fluorescence concur with published
      postmortem studies of bone lead concentration and are consistent with the
      kinetics of bone turnover and secular trends in lead exposure. These data help to
      establish a reference range for assessing the lead burden of other populations
      with environmental or occupational lead exposure.

PMID- 8277546
TI  - No structural mutation in the dopamine D2 receptor gene in alcoholism or
      schizophrenia. Analysis using denaturing gradient gel electrophoresis.
AB  - OBJECTIVE: To examine the dopamine D2 receptor (DRD2) gene coding sequences for
      abnormalities associated with schizophrenia or alcoholism and thereby help to
      resolve the controversy surrounding the reported association of alcoholism with a
      restriction fragment length polymorphism located close to the DRD2 gene. DESIGN:
      Mutational analysis of complete DRD2 gene coding sequences by denaturing gradient
      gel electrophoresis followed by direct nucleotide sequencing of detected
      variants. SETTING: Patients and controls from clinical and epidemiologic
      collections in the United States and Europe. PATIENTS: A total of 253 unrelated
      individuals, including 106 patients with schizophrenia, 113 with alcoholism, and
      34 controls. For alcoholism we included patients from previously published series
      in which an association of illness with allele A1 was reported (Taql site 3' to
      the DRD2 gene) and from other published series in which nonconfirmations of this
      association were reported. Nearly all persons examined were white. MAIN OUTCOME
      MEASURES: Frequency of nonsilent variations in DRD2 gene DNA sequences in the
      different diagnostic groups. RESULTS: We found three infrequent DNA variants that
      predict altered amino acid sequence of the receptor. None of these is associated
      with either alcoholism or schizophrenia. CONCLUSION: No structural coding
      abnormalities in the DRD2 gene are present in alcoholism or schizophrenia.

PMID- 8277547
TI  - Increasing the completion of the durable power of attorney for health care. A
      randomized, controlled trial.
AB  - OBJECTIVE: Wider use of written advance directives may prevent many ethical
      dilemmas about life-sustaining interventions for patients who have lost decision
      making capacity. We investigated whether a simple educational intervention
      increased patient completion of the durable power of attorney for health care.
      DESIGN: A randomized, controlled trial. SETTING: A health maintenance
      organization. SUBJECTS: All patients aged 65 years and older and discharged from
      a hospital between January 1991 and May 1991 (n = 1101) were randomized to either
      an intervention group or a control group. INTERVENTION: An educational pamphlet
      on the durable power of attorney for health care and a durable power of attorney
      for health care form were mailed to all patients in the intervention group. The
      control group received conventional care only. MAIN OUTCOME MEASURE: Completion
      of the durable power of attorney for health care form. RESULTS: There were no
      significant baseline differences between the intervention group and the control
      group. Following our intervention, 18.5% of the subjects in the experimental
      group completed a durable power of attorney for health care form, compared with
      0.4% of the control group (P < .0001). CONCLUSIONS: A simple educational
      intervention significantly increased the completion of the durable power of
      attorney for health care. Our findings should stimulate further efforts to
      empower patients to make informed decisions about their health care.

PMID- 8277548
TI  - Sclerodermalike esophageal disease in children breast-fed by mothers with
      silicone breast implants.
AB  - OBJECTIVE: To determine whether breast-fed children of mothers with silicone
      implants are at increased risk for the development of sclerodermalike esophageal
      involvement compared with children not exposed to silicone implants. DESIGN: Case
      series [corrected]. SETTING: Referral-based pediatric gastroenterology clinic.
      PATIENTS: Eleven children (mean age, 6.0 years; range, 1.5 to 13 years; six boys
      and five girls) referred for abdominal pain who were born to mothers who had
      silicone breast implants (eight breast-fed children and three bottle-fed) were
      compared with 17 patients (mean age, 10.7 years; range, 2 to 18 years; 11 boys
      and six girls) with abdominal pain who were not exposed to silicone implants.
      METHODS: All children underwent esophageal manometry and upper intestinal
      endoscopy with esophageal biopsy and were tested for antinuclear antibody and
      autoantibodies to Scl-70, centromere, ribonucleoprotein, Sm, Ro, La, and
      phospholipid. RESULTS: Six of the eight breast-fed children from mothers with
      silicone implants had significantly abnormal esophageal motility with nearly
      absent peristalsis in the distal two thirds of the esophagus and decreased lower
      sphincter pressure. Upper esophageal pressures and motility were normal. Compared
      with controls, the breast-fed children had significantly decreased lower
      sphincter pressure and abnormal esophageal wave propagation. These manometric
      abnormalities were not seen in the three bottle-fed children. There was no
      difference in the expression of autoantibodies in the breast-fed children
      compared with the bottle-fed children or controls. CONCLUSIONS: A relationship
      appears to exist between breast-feeding by mothers with silicone implants and
      abnormal esophageal motility. Studies evaluating larger numbers of children are
      needed to determine the extent of the risk.

PMID- 8277549
TI  - Alpha 1-antitrypsin deficiency. Impact of genetic discovery on medicine and
      society.
AB  - An increasing body of molecular information resulting from advances in basic
      research is being incorporated into clinical practice by medical genetics. The
      process by which these research advances progress from the laboratory to the
      bedside and their medical, social, and legal impact is a topic of intense current
      interest. Some authors have claimed that new genetic information may lead to
      discrimination in insurance and employment; change the way courts allocate
      responsibility for injury and resultant damages; and be inappropriately
      interpreted by the medical profession. To address some of these issues, we chose,
      as a model, to review alpha 1-antitrypsin deficiency, described over 30 years
      ago. At this time, such concerns with respect to alpha 1-antitrypsin deficiency
      have not yet been realized, perhaps for the following reasons: (1) knowledge of
      alpha 1-antitrypsin deficiency, while common among geneticists and
      pulmonologists, has not been well disseminated in the medical community; (2)
      insurers, employers, lawyers, and judges are not generally aware of the
      deficiency and its implications; (3) insurers, if they are aware of the
      deficiency, have not found it cost-effective to screen for the condition; and (4)
      in the legal context, case law involving other types of preexisting conditions is
      being applied to genetic predispositions.

PMID- 8277550
TI  - Frequent asymptomatic pulmonary embolism in patients with deep venous thrombosis.
AB  - OBJECTIVE: To determine the frequency of pulmonary embolism in patients admitted
      for treatment of deep venous thrombosis. DESIGN: An open, multicenter, dose
      ranging study to assess the safety and pharmacokinetic characteristics of tissue
      type plasminogen activator in deep venous thrombosis and pulmonary embolism.
      Perfusion and ventilation lung scans, chest roentgenograms, and venograms (in
      deep venous thrombosis) or pulmonary angiograms (in pulmonary embolism) were
      obtained before and 24 hours after inception of therapy. Heparin therapy was then
      administered. SETTINGS: Five tertiary-care hospitals. PATIENTS: All patients with
      suspected deep venous thrombosis or pulmonary embolism seen from August 1987
      through November 1988 entered the study if they met inclusion criteria and if the
      diagnosis was confirmed by venogram (deep venous thrombosis) or pulmonary
      angiogram (pulmonary embolism). INTERVENTIONS: All patients received tissue-type
      plasminogen activator followed by intravenous heparin therapy. MAIN OUTCOME
      MEASURES: The primary measure was the frequency of pulmonary embolism in patients
      with deep venous thrombosis who had no symptoms of pulmonary embolism. This was
      not the original purpose of the study but emerged as an important finding as the
      data were analyzed. RESULTS: Nearly 40% of patients with deep venous thrombosis
      who had no symptoms of pulmonary embolism had evidence of pulmonary embolism
      based on ventilation-perfusion scan and chest roentgenogram findings.
      CONCLUSIONS: Because all of those considered to have embolism had so-called high
      probability scan results, the frequency of embolism reported likely represents
      the minimum incidence of pulmonary embolism in patients with deep venous
      thrombosis who have no embolic symptoms. These data emphasize that venous
      thromboembolism is one disorder.

PMID- 8277551
TI  - Pediatricians' diagnostic approach to pharyngitis and impact of CLIA 1988 on
      office diagnostic tests.
AB  - OBJECTIVE: To determine the factors associated with an optimal diagnostic
      approach to a child with pharyngitis, characterize office laboratory methods for
      throat swab culture and group A streptococcal rapid antigen testing, and assess
      the potential impact of the Clinical Laboratory Improvement Amendments (CLIA) of
      1988 on the performance of these tests. DESIGN AND SETTING: Mailed survey to all
      board-certified primary care pediatricians from seven western states with
      telephone follow-up for nonrespondents. OUTCOME MEASURES: Differences in practice
      characteristics and use of office laboratory tests for physicians who usually (>
      80%) diagnose pharyngitis using a recommended approach vs those who follow this
      approach less often (< 50%); characteristics of physicians who indicate that they
      intend to discontinue office throat culture because of CLIA and those who will
      continue to perform this test also are compared. RESULTS: Responses from 531
      pediatricians were analyzed. Forty-four percent diagnosed pharyngitis
      appropriately for more than 80% of patients, and 17% did so for fewer than 50%.
      Optimal diagnosis was significantly more common among physicians who cultured
      throat swabs in their office (relative risk, 1.40; 95% confidence interval, 1.19
      to 1.66) and less common among solo practitioners (relative risk, 0.71; 95%
      confidence interval, 0.56 to 0.88). Factors that may decrease the sensitivity of
      office throat culture include short duration of incubation (59%), lack of quality
      control (51%), and limited education of the persons reading results (6%). With
      implementation of CLIA, 24% of pediatricians reported that they already have
      discontinued or will discontinue office throat culture, and 23% have discontinued
      or will discontinue antigen detection testing for group A streptococci. Those
      most likely to stop office culture include solo practitioners and practitioners
      who do not currently perform quality control of culture methods. CONCLUSIONS:
      Office culture for group A streptococci is strongly associated with an optimal
      diagnostic approach. Implementation of CLIA regulations may substantially
      decrease the number of physicians who perform this test. The balance between
      potential improvements in the quality of office culture with CLIA implementation
      and the decreased availability of this test needs to be assessed.

PMID- 8277552
TI  - Direct measurement of lead in bone. A promising biomarker.

PMID- 8277553
TI  - Silicone implants and esophageal dysmotility. Are breast-fed infants at risk?

PMID- 8277554
TI  - [Morphology and physiology of neural circuit relating to the involuntary
      movement].
AB  - Basal ganglia and cerebellum are closely related to the involuntary movement.
      Neural circuit of these areas and chemical neuroanatomy of them were described in
      this paper.

PMID- 8277555
TI  - [Movement disorders--concept and grand classification].
AB  - Movement disorders have been coined for diseases characterized by excessive and
      abnormal movements occurring in a conscious patient. Movement disorders are
      frequent among neurologic and psychiatric patients. They have a behavioral, or
      psychiatric, component. Movement disorders are mostly associated with disordered
      function in the basal ganglia, brain stem, and cerebellum. Such diseases are
      characterized by the occurrence of involuntary movement. This paper describes
      general concept of movement disorder, and shows classification by WHO (1991) and
      by Joseph, AB. and Young, RR. (1992). The classification of WHO includes I.
      Extrapyramidal movement disorders: 1) Parkinson disease, 2) Secondary
      parkinsonism, 3) Other degenerative diseases of the basal ganglia, 4) Dystonia,
      and 5) Other extrapyramidal and movement disorders. II. Behavioral and emotional
      disorders with onset usually occurring in childhood and adolescence: 1)
      Hyperkinetic disorders, 2) Tic disorders, and 3) others.

PMID- 8277556
TI  - [Parkinsonian tremor, rigidity and flapping tremor].
AB  - Tremor occurring at rest (4-6 Hz) is considered to be one of the most
      characteristic symptoms in patients with Parkinson's disease. Yet, an early
      stages of the disease only 50% of the patients manifest resting tremor. Indeed,
      about 15% of Parkinsonian patients never display tremor at any stage of the
      disease. If tremor is present, its type is essential for differential diagnosis.
      Pill-rolling movement, for instance, is a hallmark of Parkinson's disease.
      Parkinsonian patients often show postural tremor associated with certain postures
      or movement, whereas flapping tremor is indicative of metabolic (ex: hepatic)
      encephalopathy. Parkinsonian rigidity is unique muscular rigidity. If rigidity is
      abolished by L-dopa or dopamine agonists, this provides a reliable sign for
      diagnosis of Parkinson's disease. Pathophysiology of different types of tremor is
      briefly discussed.

PMID- 8277557
TI  - [Chorea: general aspect and classification].
AB  - Chorea is a hyperkinetic involuntary movement disorder characterized by a random
      pattern of irregular muscle jerks. This movement may involve any parts of the
      body. Emotional stress or voluntary movements may exacervate chorea and sleep
      abolish it. Luys body and striatum are the most important anatomical sites to
      evoke chorea. The lesion of inner segment of pallidum or ventrolateral thalamus
      may abolish chorea. Measurements of neurotransmitter changes of Huntington's
      disease show diminution of striatal GABA neurons and preserving nigrostriatal
      dopamine neurons. Dopamine antagonists can reduce chorea because doperminergic
      hyperactivity contribute to exacervate chorea. Precise pathophysiological
      mechanism of chorea is controversial, therefore its classification is not
      established. On the clinical point of view, classification according to heredity
      is useful to make diagnosis because hereditary diseases are easily confirmed by
      family history or specific biochemical markers. There are two groups of
      underlying diseases of non hereditary chorea. One is unilateral chorea usually
      due to contralateral hemispheric lesions to chorea. Another is bilateral chorea
      usually due to degenerative, metabolic or toxic brain diseases. Recent
      identification of abnormal DNA structure (trinucleotide repeat) in Huntington's
      disease may greatly contribute to classify underlying diseases of chorea.

PMID- 8277558
TI  - [Dystonia].
AB  - Dystonia is a persistent attitude or posture in one or other of the extremes of
      athetoid movement. It may take the form of an over-extension or over-flexion of
      the hand, torsion of the spine, with arching and twisting of the back or forceful
      closure of the eyes and a fixed grimace. Dystonia is classified into idiopathic
      and symptomatic dystonia. Idiopathic dystonia is further divided into
      generalized, focal and segmental dystonia. Generalized dystonia covers classical
      torsion dystonia, paradoxical dystonia, myoclonic dystonia, dystonia with diurnal
      variation and Dopa-responsive dystonia. Dystonic tic, paroxysmal dystonia and
      hypnotic dystonia show a dystonic posture, although they are also accompanied by
      various other involuntary movements such as athetosis or chorea. Torticollis,
      writer's cramp or blepharospasm is assigned to the focal dystonia and Meige
      syndrome to the segmental dystonia. Symptomatic dystonia is observed in various
      neurological disorders, including cerebrovascular diseases, Parkinson's disease
      and Wilson's disease.

PMID- 8277559
TI  - [The classification of myoclonus].
AB  - The term "myoclonus" was originally used to indicate brief jerky involuntary
      movements. But, nowadays the meaning of myoclonus has expanded so much that its
      definition and classification have been considerably obscured. In this view, the
      definition of myoclonus is described and the characteristic clinical features are
      discussed. The classification of myoclonus is presented based on the
      pathophysiological observations. Myoclonus is divided into two large groups,
      cortical myoclonus directly associated with the activity of the motor cortex, and
      subcortical myoclonus which comprises various types of myoclonus (including
      spinal myoclonus). Furthermore, the electrophysiological aspects of myoclonus and
      its pathogenesis are briefly discussed.

PMID- 8277560
TI  - [Ballism, hemiballism].
AB  - Ballism, which is seen relatively infrequently among movement disorders, is
      characterized by the abrupt onset of vigorous, rapidly executed, poorly patterned
      in voluntary movement of the limbs. Hemiballism is mostly associated with the
      lesion in the subthalamic nucleus. However, it occasionally occurs as a result of
      lesions outside the subthalamic nucleus. The natural history of hemiballism
      caused by vascular subthalamic lesion usually shows gradual disappearance within
      days or weeks. Death from exhaustion has however been reported in some patients
      within four to six weeks after the onset. Hemiballism caused by lesions outside
      the subthalamic nucleus tends to persist for a longer period. Intensive treatment
      is therefore required. Successful treatments of hemiballism with haloperidol or
      chlorpromazine are wellknown, but, in older patients, sulpiride can be the first
      choice of medications because of its lesser side effect.

PMID- 8277561
TI  - [Athetosis].
AB  - Athetosis is a peculiar involuntary movement resulting from pathologic
      involvement of the basal ganglia. Although mechanism of this movement is still
      far from established, athetosis is clinically differentiated from chorea and
      dystonia. The purpose of this article is to review and summarise the
      classification of this involuntary movement disorder. This movement disorder is
      classified into double athetosis, chorea-athetosis, unilateral athetosis and
      pseudo-athetosis. The double athetosis is featured by increased muscle tonus and
      irregular small amplitude movement, which appears the most frequently in patients
      of cerebral palsy. In chorea-athetosis, irregular abnormal movement is more
      prominent and larger than double athetosis. This type of movement appears
      commonly in patients other than cerebral palsy. Unilateral and pseudo-athetosis
      are derived not from disturbance of the basal ganglia but from impared sensory
      pathways of the deep sensation due to cerebro-vascular lesion. Stereotactic VL
      thalamotomy is effective to relieve increased muscle tonus but not to decrease
      involuntary movement.

PMID- 8277562
TI  - [Tic disorders].
AB  - Tics are sudden, rapid, stereotyped, recurrent, nonrythmic, brief and purposeless
      involuntary movements or vocalization. The characteristics of tics is that they
      can be suppressed for certain minutes or hours. Tic disorders are classified into
      three subtypes in DSM-III. They are: transient tic chronic motor or vocal tic and
      Tourette's disorder. These three disorders are considered to be clinical
      varieties of a tic spectrum. Tic disorders are male-predominant, age-dependent
      (most tics appear by puberty) disorders. Autosomal dominant inheritance has been
      suggested in Tourette's disorder. It is highly interesting and important to
      investigate the pathogenesis of tic symptoms because tics are thought to be in
      between neurological symptoms and psychiatric symptoms.

PMID- 8277563
TI  - [Myokymia].
AB  - Myokymia is one of the involuntary movements, which is characterized by
      undulatory muscle spasm, similar to the worm's crawl. Sometimes muscle pain,
      itchy sensation, dysautonomia and other symptoms are associated with it. Cases
      showing normal neurological findings are rare. Myokymia is caused by various
      diseases, such as, multiple sclerosis, hypothyroidism, Guillan-Barre syndrome and
      so on. Generally myokymia is classified into two types, i.e. limb myokymia and
      facial myokymia according to the site. On the other hand, myokymia with
      hyperhidrosis is known as Issacs syndrome. There are many opinions about the
      pathogenesis and mechanism in the myoneural junction, peripheral nerve or spinal
      cord, however these are not established. Further investigation of myokymia is
      expected.

PMID- 8277564
TI  - [EMG for study of involuntary movements].
AB  - Involuntary movements caused by disorders in the central nervous system are
      peculiar, purposeless movements whose characteristics have been elaborately
      described in the literature of clinical neurology, although their neural
      mechanism has not yet been fully clarified. As involuntary movement is the result
      of abnormal contraction of the skeletal muscles, simultaneous recording from many
      muscles or muscle groups with different functions furnishes information on
      characteristic patterns of involuntary movements based on physiological features
      and provides us with a tool for differential diagnosis and for evaluation of the
      degree of disorder. For these purposes concurrent examination of muscle tone and
      of voluntary contraction is desirable. In this article, quantitation of movement
      and strength by EMG recorded with surface electrodes, characteristic patterns of
      EMG in various involuntary movements including tremor, chorea, ballism and
      dystonia were described.

PMID- 8277565
TI  - [EEG and polysomnography findings in patients with dyskinesia].
AB  - It is known that EEG findings reveal various abnormalities in patients with
      involuntary movement. But these findings are not specific. It has been reported
      to be related to myoclonus and spike. The other involuntary movement is unknown
      to the relation to EEG findings. The involuntary movement usually disappears
      during sleep, but a certain involuntary movement appears only during sleep. In
      the patient with Huntington's chorea and dystonia musculorum deformans, PSG
      reveals an increase in interspersed wakefulness, decrease of deep sleep and
      prolongation of REM latency. Periodic limb movement and nocturnal paroxysmal
      dystonia appear only during sleep. Nocturnal sleep studies are important for
      exploring the pathophysiology in involuntary movement.

PMID- 8277566
TI  - [Clinical diagnosis of movement disorders--evoked potentials].
AB  - As a clinical diagnostic approach, the evoked potential has been used to
      differentiate movement disorders, especially myoclonic movements, Giant
      somatosensory evoked potentials (SEPs) and long-loop reflex to electrical
      stimulation of the peripheral nerve are commonly employed in the evaluation of
      patients with myoclonus. Recently, abnormality in a specific component of SEP
      frontal N30 has been reported in focal dystonia. Jerk locked back averaging has
      been applied to cortical reflex myoclonus, minipolymyoclonus, cortical tremor,
      simple tics, chorea-acanthocytosis, Huntington's chorea, etc. Silent period
      locked averaging is also used for asterixis. With these new electrophysiological
      techniques, evaluation of functional mechanisms in movement disorders may be
      expected, with fruitful results.

PMID- 8277567
TI  - [Neuroimaging in movement disorders--CT, MRI, and PET study].
AB  - The recent advance in non-invasive methods of neuroradiology such as magnetic
      resonance imaging (MRI) and positron emission tomography (PET) has been lead to
      give us much informations about the structural changes with high resolution, the
      iron distribution in the brain, the regional metabolism, and the receptor mapping
      etc. These new methods have been also applied to the movement disorders. For
      example, in Parkinson's disease, MRI revealed the narrowed T2 image of pars
      compacta of nigra without striate lesion. Also PET in this disease demonstrated
      normal regional cerebral blood flow, normal regional glucose metabolism,
      decreased uptake of DOPA, reduced re-uptake of dopamine, and normal D1 and D2
      receptors in the striatum. These anatomical, metabolic, and molecular physiologic
      information has not only elucidated the pathophysiology but has also helped us to
      understand normal brain function.

PMID- 8277568
TI  - [Dyskinesia in various diseases--cerebrovascular disease, head injury, brain
      tumor].
AB  - In the broad sense of the term, dyskinesia refers to the overall spectrum of
      abnormal involuntary movement. Abnormal involuntary movement includes
      parkinsonism, chorea, athetosis, myoclonus and ballism. Clinically, the most
      frequently encountered form of dyskinesia is parkinsonism. In addition to
      parkinsonism, typical forms of dyskinesia caused by cerebrovascular disease, head
      injury and brain tumor, based on a review of the literature and our own
      experience are discussed.

PMID- 8277569
TI  - [Dyskinesia in metabolic encephalopathy].
AB  - We have described several kinds of involuntary movements occurring in metabolic
      encephalopathies. They are often associated with slowing of
      electroencephalographic basic activities and with loss of consciousness.
      Laboratory studies disclose the cause of the encephalopathies. Asterixis, first
      reported in hepatic encephalopathy, is produced by EMG silence during voluntary
      contraction. Myoclonus is associated with a short excessive EMG discharges.
      Tremor is caused by grouping EMG discharges. Some other kinds of involuntary
      movements are seen in metabolic encephalopathies. Clinical features of hepatic,
      uremic, hypoxic, and hypoglycemic encephalopathies are briefly described.

PMID- 8277570
TI  - [Dyskinesias in infections of the central nervous system].
AB  - Dyskinesia, here, is considered to be synonymous with abnormal involuntary
      movement (AIM). AIMs are recognized in various infections of the central nervous
      system, of which Creutzfeldt-Jakob disease (CJD) and subacute sclerosing
      panencephalitis (SSPE) are thought to be the most important. The two show
      myoclonus and other similar features in common except age of onset. The myoclonus
      is classified under the non-stimulus-sensitive and periodic one characterized by
      a long duration and a relationship to periodic synchronous discharge (PSD) in
      EEG. The rhythm is, however, somewhat different and quicker in CJD (0.5-2 Hz)
      than in SSPE (0.05-0.2 Hz). In the acquired immunodeficiency syndrome (AIDS),
      AIMs, including tremor, myoclonus and some others are also noted.

PMID- 8277571
TI  - [Dyskinesias as neurologic complications of hematologic disorders].
AB  - Dyskinesias as the neurologic complications of hematologic disorders were
      described in detail on abetalipoproteinemia and ataxia telangiectasia as well as
      in summary on other hematologic diseases. Dyskinesias as the iatrogenic
      neurologic manifestations in hematologic disorders were also briefly described.
      Although the pathogenetic mechanisms of dyskinesias observed in hematologic
      disorders were quite heterogeneous, they could provide us with good suggestions
      and clues to clarify the true mechanisms of their own as well as other
      dyskinesias.

PMID- 8277572
TI  - [Movement disorders in miscellaneous disorders--inherited metabolic diseases].
AB  - A variety of inheritable metabolic disorders produce movement disorders. A lists
      of conditions associated with tremor, athetosis, chorea, dystonia and myoclonus
      are presented as a guide for the differential diagnosis of such abnormal
      involuntary movements. The list includes aminoacidopathies, lipidoses,
      mucopolysaccharidoses, mucolipidoses, organic acidemias, mitochondrial
      cytopathies and disorders of carbohydrate, purine, and metal metabolism.
      Clinical, pathological and biochemical features of movement disorders of three
      typical examples, Wilson's disease, Lesch-Nyhan syndrome and glutaric acidemia
      type 1, are described.

PMID- 8277573
TI  - [Extrapyramidal syndrome induced by chemical substances].
AB  - Extrapyramidal signs are frequently observed in toxic diseases due to
      environmental and industrial chemical substances. The predominant manifestations
      are Parkinsonism and less frequently tremor. Parkinsonism has been described
      among the toxic diseases due to carbon monoxide, hydrogen sulfide, and hydrogen
      cyanide. In these diseases, Parkinsonism used to appear in the recovery stage
      from coma in the severe cases. This was also true in methyl alcohol poisoning.
      The extrapyramidal signs are usually symmetrical. Akinesia and rigidity are main
      features. Tremor is absent or mild. Levodopa and the other antiparkinsonian drugs
      are not so effective. Brain CT studies have revealed symmetrical low density
      areas in the globus pallidus and putamen. On the other hand, postural tremor is
      main neurological findings in the poisonings by inorganic mercury and tetraethyl
      lead. In general, tremor in the toxic disease is reported to be self-limited.

PMID- 8277574
TI  - [Genetics in movement disorders].
AB  - Genetic considerations in movement disorders are described. 1) Familial
      parkinsonisms are heterogeneous; genes for two of them, 'Lubag' and Waisman
      syndrome have been mapped to X chromosome, though genes for others do not have
      been mapped. 2) The responsible gene for Huntington's disease has been cloned
      recently and named huntingtin. A (CAG)n repeat longer than the normal range was
      observed in huntingtin gene. The (CAG)n repeat appears to be located within the
      coding sequence of a predicted approximately 348 kD protein that is widely
      expressed but unrelated to any known gene. The expansion of an unstable
      trinucleotide CAG repeat are also the causes of hereditary neurodegenerative
      diseases such as X-linked bular and spinal muscular atrophy and spinocerebellar
      ataxia type 1. 3) There are various forms in hereditary dystonia. Although the
      responsible gene for idiopathic torsion dystonia, inherited as an autosomal
      dominant pattern, has been mapped to 9q 32-34, genes for others do not have been
      mapped. 4) The Gilles des la Tourette syndrome (GTS) is a hereditary,
      neuropsychiatric-neurobehavioral disorder with childhood onset that is
      characterized by motor and vocal tics. About 80% of the human genome could be
      excluded as possible site for the GTS gene by studies with over 600 DNA markers
      in an international collaborative effort, but actual localization has not yet
      been accomplished.

PMID- 8277575
TI  - [Surgical treatment of Parkinson's disease].
AB  - Surgical treatment for Parkinson's disease began by blocking of the pyramidal
      system in early part of this era. In 1942, Meyers performed Ansotomy for the
      treatment of Parkinsonism without leaving hemiplegia, leading subsequent
      operating target to blocking of pallidofugal fiber. Then, the development of
      stereotaxy in 1947 caused an operative progress to Pallidotomy and further to
      Thalamotomy. Although the spread of levodopa therapy gradually brought about
      decline of surgical treatment, Thalamotomy became to be reexamined in view of not
      a little problems about and side effects of levodopa therapy. With the
      development of CT, MRI and the like, Thalamotomy via MRI-stereotaxy was
      developed, making operations safer and surer. Besides, transplantation of
      dopamine neurons into the striatum was tried as an essential treatment and is in
      clinical application via animal experiments. Fetal ventral mesencephalic tissue
      and adrenal medullary tissue are available therefore, but demerits are such that
      the former poses some ethical problem and the latter is poor and short-lived
      response. The transplantation of stellate ganglion into the striatum, which we
      have recently developed is safe and more effective than the adrenal medullary
      tissue. The respective one thirds of the cases did without levodopa following
      transplantation, needed half as much as the preoperative levodopa dose and needed
      the same as the latter. Although Horner's syndrome was noted in all cases
      following transplantation, no Parkinson syndrome became aggravated in any one of
      the cases.

PMID- 8277576
TI  - [Multiple system atrophy (MSA)].
AB  - Sporadic olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome (SDS),
      striatonigral degeneration (SND) are classified as multiple system atrophy (MSA),
      based on their clinicopathological findings. These clinical features,
      neuroimaging including CT, MRI, PET and SPECT findings, autonomic function test,
      pathological findings and treatments are reviewed. Several advances such as
      noradrenaline loading test, low signal intensity on T2 weighted image on super
      conductive MRI and glial cytoplasmic inclusions in the central nervous system on
      pathological finding are notable. However, unsatisfactory medical treatment for
      MSA must be resolved in a near future.

PMID- 8277577
TI  - [Hallervorden-Spatz disease].
AB  - Hallervorden-Spatz disease is an autosomal recessive disorder which usually
      begins in childhood, progresses irreversibly and leads to death in early
      adulthood. The main manifestations are extrapyramidal signs, such as, dystonia
      and rigidity, pyramidal signs and mental deterioration. Pathological changes are
      found mainly in globus pallidus. They are characterized by (1) pigmentation with
      iron, and (2) numerous spheroids which represent abnormal axonal swelling. The
      cause of the disease is not clear but excessive iron storage may contribute to
      pathogenesis. The patients are treated symptomatically. The definite diagnosis is
      difficult and is made post mortem. Recently, however, characteristic MRI findings
      has been reported, which may be useful for the diagnosis during life.

PMID- 8277578
TI  - [Benign non-progressive familial chorea].
AB  - Benign non-progressive familiar chorea is a chronic childhood (less than 5 years)
      choreatic disorder inherited as an autosomal dominant trait but not associated
      with dementia or progressive motor dysfunction. The major feature of this disease
      is chorea with early insidious onset and an arrested progression. The lack of
      mental retardation, mental deterioration or convulsion is the other significant
      aspects of this disorder. The chorea usually involves the distal limbs, face and
      trunk. This does not progress to a profound degree throughout the life. There is
      a controversy regarding whether this benign disorder might be a subtype variant
      of Huntington's disease. This should be clarified by more extensive molecular
      genetic studies of this disease.

PMID- 8277579
TI  - [Tardive dyskinesia--diagnosis and treatment].
AB  - Tardive dyskinesia is defined as a syndrome consisting of abnormal, stereotypical
      involuntary movements usually of choreoathetoid type, principally affected the
      mouth, face, limbs and trunk, which occurs relatively late in the course of
      neuroleptic drug treatment and in the etiology of which the drug treatment is a
      necessary factor. Presently, the prevalence of tardive dyskinesia in the
      hospitalized patients in psychiatric hospitals in Japan is estimated to be 20
      30%. Epidemiology, possible pathophysiology and symptomatology of tardive
      dyskinesia are briefly described. Differential diagnosis between this syndrome
      and other involuntary movements such as psychotic mannerism, senile orofacial
      dyskinesia, rabbit's syndrome, Pisa syndrome or Meige's syndrome is discussed.
      Several drugs to suppress involuntary movements of tardive dyskinesia are
      described. However, there appears to be no consistently reliable therapies for
      patients who develop the tardive dyskinesia. Treatment for this syndrome, other
      than neuroleptic withdrawal, are still uncertain.

PMID- 8277580
TI  - [Oral dyskinesis, facial dystonia].
AB  - Oral dyskinesia or orofacial dyskinesia is considered to be one of the most
      severe side-effects of a chronic treatment with neuroleptics or 1-dopa, although
      it has also been described in nontreated people. In oral or orofacial dyskinesia,
      involuntary spasms cause arrhythmic movements of the tongue, sometimes with
      protrusion and drooling, opening of the mouth, clenching of the teeth, or
      pursuing and retraction of the lips. Each spasm lasts seconds to a minute or two.
      In orofacial dyskinesia, lip smacking, chewing and tongue movements occur in a
      repetitive pattern interrupting speech. The pathophysiology of the orofacial
      dyskinesia has been still unknown. However, previous clinical observations and
      basic pharmacological studies have suggested that the dopaminergic receptors,
      especially of D1 type, play a crucial role in causing this condition. Based on
      this assumption, dopaminergic receptor antagonists have been introduced as
      medical treatments.

PMID- 8277581
TI  - [Palato-pharyngo-laryngeal myoclonus].
AB  - Palato-pharyngo-laryngeal myoclonus is well-known clinical criterion
      characterized by persistent, rapid, repetitive, rhythmic muscle twitch the rate
      of which ranges 50-200 Hz. It appears in the palate, pharynx, larynx, diaphragma,
      and the ocular or limb muscles, but the most common combination of the
      distribution is palate-pharyngo-laryngeal type or only palatal type. In most
      instances the movement is synchronous, but others show asynchronous myoclonus at
      different rates. There was a case report in which an electrical stimulation given
      at the ulnar nerve produced reset of myoclonus indicating that some feedback
      mechanism has some influence in the generation of pacemaker activity in the
      brainstem. This myoclonus has been considered to result from interruption of any
      one fiber system in a olivocerebellorubrotegment-olivary equipotential reverating
      circuit, so-called Guillain-Mollaret triangle. As etiological factors,
      cerebrovascular accidents are the most common, but various other causes have been
      encountered including tumor, trauma, inflammation, multiple sclerosis,
      electroshock, dialysis encephalopathy, and other degenerative neurological
      diseases. Analysis of the symptoms is the most important cure of the diagnosis,
      and this myoclonus is relatively easily differentiated from other involuntary
      movement, but recently MRI is a very effective examination to detect a lesion in
      the medulla visualizing the degenerative changes of the lower olivary nucleus.
      Clonazepam, trihexyphenidyl, carbamazepine, 5HTP and caeruletin have been
      reported as effective agents for this movement.

PMID- 8277582
TI  - [Negative myoclonus].
AB  - Negative myoclonus is an involuntary movement produced by a short interruption of
      muscle contraction. In this paper, recent concepts, pathomechanisms and treatment
      in negative myoclonus are reviewed. Two patients with negative myoclonus are also
      presented. One is an 18-year-old girl with Gaucher disease, and the other is a 14
      year-old boy with simple partial motor epilepsy. Electrical silent period was
      demonstrated when negative myoclonus was clinically observed. In both patients,
      somatosensory evoked potentials showed giant responses, which may indicate that
      mechanisms of negative myoclonus have a relationship with cortical abnormal
      excitability.

PMID- 8277583
TI  - [Movement disorders in HTLV-I associated myelopathy (HAM)].
AB  - Periodic movements in sleep (nocturnal myoclonus) are characterized by a triple
      flexion of the ankle, knee and hip, which are particularly evident during 1-2 and
      2-3 sleep stages. Iijima et al (1991) reported these movements in 5 out of 7 HAM
      patients, suggesting that nocturnal myoclonus is not rare in HAM. L-dopa and
      bromocriptine are reported to be the most effective. Spinal myoclonus (SM) is
      characterized by symmetric, rhythmic involuntary contractions of muscle groups
      supplied by one or several contiguous segments of the spinal cord. There has been
      only one case report of SM by Kanda et al (1988). Clonazepam and tetrabenazine
      are reported to be the most effective. Tremor is characterized by a sinusoidal
      oscillatory movement produced by synchronous or alternating contractions of
      reciprocally innervated antagonist muscles. Postural finger tremor was seen in
      about 40% of HAM patients (Suwazono et al, 1989). Painful, paroxysmal muscle
      contractions of the lower limbs were reported in only one patient with HAM by
      Ikeda et al in 1990. Based on electrophysiological findings, they were thought to
      be caused by reciprocal excitation in the spinal cord.

PMID- 8277584
TI  - [Diagnosis and therapy of epilepsy and myoclonus].
AB  - The pathogenesis oriented diagnoses and therapies of epilepsy and myoclonus was
      tended to describe, but their pathogeneses were partially elucidated. The
      pathogenesis of both diseases was firstly demonstrated to have genuine or
      hereditary factors to be discharged abnormal electrical potentials which were
      provoked varieties of symptoms of both epilepsy and myoclonus. The careful
      observation of clinical symptoms, the introduction of monitoring EEG, computed
      tomogram, spike voltage topography, magnetoencephalography, somatosensory evoked
      potential (SEP) and MRI were comparatively easily provided the diagnoses of both
      diseases and topographical foci of abnormal discharge. The diagnosis of myoclonus
      was more difficult than those of epilepsy, because the clarification of
      pathogenesis and definition of diagnosis was lacked. The therapies of both
      epilepsy and myoclonus were surgically removed the topographically abnormal
      discharged focus to be congenital or secondary, and their conventional discharge,
      monitoring the findings of EEG, and checking out the clinical symptoms and side
      effects of drugs. We suggest that the clear-cut description on diagnoses and
      therapies of both disease are required to be further investigated.

PMID- 8277585
TI  - [Hereditary dentatorubro-pallidoluysian atrophy (DRPLA): clinical studies on 45
      cases].
AB  - The term of dentatorubral and Pallidoluysian atrophy (DRPLA) was first introduced
      by Smith, who proposed that there was a combination of cerebellar ataxia with
      choreoathetosis based on DRPL lesions. In 1972, Naito et al. reported two
      families with progressive myoclonus epilepsy (PME) syndrome with cerebellar
      ataxia, and hyperactive deep tendon reflexes. In 1977, Oyanagi et al. reported 4
      autopsied cases of PME, and pointed out degenerative lesions in the DRPL systems.
      In 1982, Naito and Oyanagi reported this type of PME to be hereditary DRPLA, with
      a clinicopathological disease entity. This type of PME with DRPLA has been made a
      major category, especially in Japan. In this article, clinicopathological
      features of the hereditary DRPLA will be reviewed on the basis of 45 patients
      with this disease. The disease was inherited as an autosomal dominant fashion,
      and induces a wide rage of clinical features depending upon the age of onset,
      ranging from 3 years to 69 years of age. The initial symptoms were variable
      according to the age of onset and mental retardation was the most prominent
      symptom in the patients in which the disease started in the first decade and with
      an epileptic seizure in the second decade. In the following next two decades, the
      incidence of epileptic seizure, as initial symptoms was decreased to 23% and gait
      disturbance and ataxia in 38% of the patients, which increased to 73% in the 5th
      and 6th decades. The cardinal symptoms of hereditary DRPLA includes mental
      retardation, epileptic seizure and myoclonus, cerebellar ataxia with gait
      disturbances, psychological symptoms including clonus, cerebellar ataxia with
      gait disturbances, psychological symptoms including character changes, and
      dementia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277586
TI  - [Stiff-man syndrome].
AB  - The Stiff-man syndrome is a rare disease, which is characterized by continuous
      muscular rigidity and painful muscle spasm. Although large dose diazepam,
      baclofen, clonazepam, or clonidine benefit the symptoms significantly, the
      pathophysiology had been unknown until recently. In 1988 and 1990, Solimena et
      al. reported autoantibody against glutamic acid decarboxylase in sera and
      cerebrospinal fluids. Plasmapheresis was then applied to a patient with this
      syndrome, and the symptoms and the electromyographic activities decreased
      dramatically. The syndrome is likely to be an autoimmune disease, but further
      detailed studies are required as to the cause and pathophysiology and
      immunological treatment must should be established.

PMID- 8277587
TI  - [Crystal structure and function of pyrimidine dimer specific excision repair
      enzyme: T4 endonuclease V].
AB  - Bacteriophage T4 endonuclease V is an enzyme which plays an important role in
      pyrimidine dimer specific excision repair of DNA. This enzyme possesses two
      distinct catalytic activities, pyrimidine dimer glycosylase and apyrimidinic
      endonuclease. The three dimensional structure (3D) of the wild type enzyme was
      determined at 1.45A resolution by X-ray crystallography. In combination with the
      results of site-directed mutagenesis, the refined structure revealed that Glu23
      and the surrounding basic residues constitute the catalytic center of this
      enzyme. Furthermore, the 3D structure of active site mutants were determined and
      compared with that of the wild type. The results suggest that a precise
      configuration of Glu23 residue is required for glycosylation and that Arg3 plays
      an important role in the substrate binding.

PMID- 8277588
TI  - [Development of intelligent DDS technologies].
AB  - Recently, biologically active therapeutic peptides have been artificially
      synthesized by genetic engineering techniques. These peptides are easily degraded
      under physiological conditions and also encounter absorption problems due to
      their high molecular weight. Hence, they cannot be utilized effectively in
      conventional dosage forms. For such active agents, new types of DDS must be
      developed to deliver the drug effectively to the target site (targeted, site
      specific delivery) and release drug when drug is required (temporal control) in
      addition to conventional rate-controlling systems. To realize such drug release
      systems, it is important to construct a system where drug itself senses an
      environmental stimuli and responds to appropriately control drug release. Such
      systems are described as "intelligent DDS", as distinguished from conventional
      DDS.

PMID- 8277589
TI  - [Structure of ADP-ribosylating enzyme and DNA repair].
AB  - ADP-ribosylation is a post-translational modification of protein using a
      respiratory coenzyme, NAD+, as a substrate. Poly(ADP-ribosyl)ation reaction in
      the nuclei has been thought to be involved in DNA repair. Cloning of poly(ADP
      ribose)polymerase cDNA and gene has opened the way for analyzing the structure
      and functions of poly(ADP-ribose)polymerase at the molecular level. Poly(ADP
      ribose)polymerase is a zinc-finger protein and binds to nicks of DNA. This enzyme
      is activated by binding to DNA and poly(ADP-ribosyl)ates nuclear proteins and
      poly(ADP-ribose)polymerase itself. Structural analysis of poly(ADP
      ribose)polymerase from different classes has shown conserved motifs in the domain
      structures. In this review, recent advances in this field, including mono-ADP
      ribosylation and cyclic ADP-ribose, are described.

PMID- 8277590
TI  - [Association of parents' occupational exposure to cancer in children. A case
      control study of acute lymphoblastic leukemia].
AB  - The objectives of the present study were to evaluate the preconceptual, prenatal,
      and postnatal environmental factors as possible etiologic agents of childhood
      neoplasms. An exploratory case-control study was conducted on parents of children
      less than 15 yr of age with acute lymphocytic leukemia (ALL). Data were obtained
      on 147 identified cases by interview from their mothers and by mail questionnaire
      from their fathers. Hospital control cases were matched by sex and age, while
      population control cases were matched by place of residence, and sex. The
      following results were obtained. 1) As for the occupation of the parents, more
      fathers of the cases were engaged in occupations related to agriculture,
      medicine, and science than those of the controls, and more mothers of the cases
      were engaged in agriculture than those of the controls. 2) No significant
      relation could be demonstrated between ALL and occupations related to hydrocarbon
      and ionizing radiation. 3) The results of multivariate analysis showed that in
      comparison with the hospital control cases the preconceptual exposure to
      chemicals and the prenatal exposure to pesticides of the fathers and the prenatal
      exposure to benzine and spray pesticides of the mothers were risks of high
      significance. In comparison with population control cases, the prenatal exposure
      of benzine and exposure to paints of the mothers prior to disease onset were
      risks of high significance. The foregoing results suggest that exposure to
      occupational and environmental factors of the parents may play an etiologic role
      in childhood leukemia.

PMID- 8277591
TI  - [Musculoskeletal symptoms and working postures in pear and apple orchard
      workers].
AB  - Musculoskeletal symptoms in pear and apple orchard workers were studied in
      relation to working postures, particularly arm elevation and head extension. The
      same forty-six female workers were examined three times; in May while thinning
      pears, in June while bagging pears, and in July while bagging apples.
      Musculoskeletal symptoms in the neck and shoulders were predominant in thinning
      and bagging pears when compared with bagging apples. When thinning pears, there
      was a significantly higher prevalence of complaints of stiffness and pain in the
      neck and shoulders, pain in the upper and lower back, muscle tenderness in the
      shoulders and forearm, and decreased back muscle power. When bagging pears, there
      was a significant difference in complaints of stiffness and pain in the neck and
      shoulders, muscle tenderness in the shoulders, and pain in motion of the neck
      joint. Pear tasks require more arm elevation and head extension than apple tasks.
      The working postures of arm elevation and head extension were considered to be a
      dominant causative factor in shoulder-neck disorders of the workers examined. The
      low back pain from thinning pears may be related with continuous backward bending
      of the back associated with the thinning work.

PMID- 8277592
TI  - [Studies on the determination of delta-aminolevulinic acid in plasma and blood,
      the effect of sample storage, and the comparison between both values].

PMID- 8277594
TI  - [The 23rd Regional Meeting of East and West of Japan, Japanese Society of
      Nephrology. Abstracts].

PMID- 8277593
TI  - [Occupational dust exposure and prevalence of respiratory symptoms among conduit
      repair workers].
AB  - The amount of water supply in Japan was 16 billion ton as of 1989. Water from
      rivers and other sources is purified, sterilized and then supplied to the
      residents through conduits. When conduits are accidentally damaged, they must be
      repaired by the workers of the Waterworks Bureau of the local government. In this
      task, the workers are exposed to airborne dust which develops while digging and
      filling the ground and cutting the conduit and the concrete covering the road.
      The purpose of the present study was to estimate the airborne dust exposure level
      among the workers and to investigate its effect on their respiratory organs.
      First, we measured the total dust exposure concentration of 20 conduit repair
      workers and the total dust concentration in 10 office rooms. Second, we conducted
      a self-administered questionnaire survey to estimate the prevalence of
      respiratory symptoms among the employees of 119 Waterworks Bureaus. The subjects
      of the analysis were 322 conduit repair workers and as their controls 345
      clerical/engineering workers. The results can be summarized as follows: 1) The
      average daily total dust exposure while repairing conduits ranged from 0.27 to
      5.05 mg/m3 (mean = 0.91 mg/m3), while that while exchanging water meters from
      0.23 to 0.52 mg/m3 (mean 0.41 mg/m3). These values were 4.6 and 2.1 fold higher
      than the total dust concentration in office rooms (mean = 0.20 mg/m3). 2) With
      the use of fluorescent X-ray method, iron and aluminum were detected in all
      samples collected while repairing conduits and the intensity of X-ray increased
      with increase in weight of collected dust. Iron exposure concentration ranged
      from 0.006 to 0.095 mg/m3, which is much higher than the levels in the air in
      urban areas. Iron and aluminum could not be detected by fluorescent X-ray method
      in most of the samples collected in office rooms. These findings indicate that
      the main element in the dust collected while repairing conduits is soil, while
      that in office rooms is tobacco smoke. 3) Among the smokers, the prevalence of
      cough and phlegm was significantly higher in conduit repair workers than in
      clerical/engineering workers. A similar tendency was observed among ex-smokers
      and non-smokers, but the difference was not significant.

PMID- 8277595
TI  - [Usefulness of blood disappearance corrected hepatic uptake ratio (LHL/HH) as a
      hepatic functional index using 99mTc-galactosyl serum albumin].
AB  - The authors introduced blood disappearance corrected hepatic uptake ratio
      (LHL/HH) as an index of hepatic function using 185 MBq/3 mg of 99mTc-galactosyl
      serum albumin (GSA). Three ratio parameters, the hepatic uptake ratio (LHL15),
      blood disappearance ratio (HH15), and LHL15 divided by HH15 (LHL/HH) were
      evaluated with percent injected dose of 99mTc-GSA in blood at 15 min after
      injection (%ID15) and hepatic functional severity graded by Child-Turcotte
      criteria score. Seventy eight patients with chronic liver disease were studied.
      There was a poor linear correlation between the LHL15 and %ID15, because the
      LHL15 formed a plateau phase in the lower-value range for %ID15. In contrast,
      LHL/HH showed an excellent linear correlation with %ID15 in its whole range. In
      the comparison with the clinical functional severity, LHL/HH gave a more highly
      significant difference (p < 0.001) than LHL15 (p = 0.005) between the normal and
      mild dysfunction groups and gave a significant difference (p = 0.032) between the
      mild and moderate groups, in which HH15 showed no meaningful difference (p =
      0.07). This index is obtained with no difficult procedures and can be regarded as
      a unified parameter for hepatic uptake and blood disappearance. It is hoped that
      LHL/HH will prove useful in the diagnosis of hepatic functional severity using
      99mTc-GSA.

PMID- 8277596
TI  - [Quantitative regional cerebral blood flow study with 123I-IMP in patients with
      dementia and in patients with poor activities of daily living].
AB  - N-isopropyl-p[123I]iodoamphetamine (123I-IMP) SPECT and quantitative regional
      cerebral blood flow (rCBF) studies were performed in 111 patients with cerebral
      disorders. Continuous arterial blood sampling method based on the microsphere
      model was used as a quantitative rCBF measurement. We evaluated rCBF in patients
      with dementia and also in patients with poor activities of daily living (ADL).
      Patients with dementia showed significant reduction of mean CBF in contrast to
      patients without dementia. Significant decrease of rCBF in the bilateral frontal
      cortex, parietal cortex and basal ganglia and the right temporal cortex were
      found in demented patients. Although patients with vascular dementia showed
      decreased rCBF in bilateral basal ganglia, demented patients with Parkinson's
      disease showed no significant reduction of rCBF in any regions. Patients with
      poor ADL showed decreased rCBF in all brain regions. And particularly frontal and
      basal ganglionic defects were most pronounced. Patients with poor ADL resulted
      from cerebral infarction showed significant decrease of rCBF in bilateral basal
      ganglia. However, there was no significant correlation in Parkinson's disease
      between ADL and rCBF. The rCBF measurement with 123I-IMP is useful for clinical
      evaluation of demented patients and patients with poor ADL.

PMID- 8277597
TI  - [Changes in arterial blood flow patterns by patients' posture during hepatic
      arterial infusion chemotherapy assessed by 99mTc-MAA perfusion scintigraphy].
AB  - Hepatic arterial perfusion scintigraphy (HAPS) with 99mTc-macroaggregated albumin
      (MAA) was performed to reveal the effect of patients' posture for the arterial
      blood flow patterns in hepatic arterial infusion (HAI) chemotherapy. 20 patients
      of liver metastases with the percutaneously implanted catheter into the hepatic
      artery underwent HAPS following administration of 99mTc-MAA at the supine and the
      upright position under one week interval. 10 ml of the saline with radionuclide
      was injected at a rate of 1 ml per minute. Acquired two images at the different
      position of each patient were compared and grouped into three classes; similar,
      slightly different and different. Of 20 patients, 6 (30%) were judged as similar,
      8 (40%) as slightly different, and 6 (30%) as different. These results suggest
      that the drug distribution can change by patients' posture in case of the slow
      rate HAI performed with continuous infusion pump.

PMID- 8277598
TI  - [The distribution and kinetics of 123I-MIBG in normal human hearts].
AB  - 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in
      twelve normal human subjects, and the distribution and clearance of MIBG were
      estimated. In PLANAR studies, heart to mediastinum (H/M) and lung to mediastinum
      activity ratio (L/M) were 2.68 +/- 0.45 and 1.82 +/- 0.23 in initial images, and
      2.75 +/- 0.44 and 1.55 +/- 0.13 in delayed images. The clearance of MIBG in the
      lung was more rapid than that in the heart, 41.6 +/- 4.1 vs. 29.8 +/- 3.2 (%),
      therefore MIBG cardiac profiles were more clarified in delayed images. In SPECT
      studies, the regional relative uptake (RRU) in anterior, septal, inferior and
      lateral wall were 100.0 +/- 0, 93.9 +/- 6.9, 85.0 +/- 10.0 and 104.9 +/- 8.3 (%)
      in initial images, and 100.0 +/- 0, 96.8 +/- 9.6, 79.4 +/- 8.3 and 99.1 +/- 7.9
      (%) in delayed images, respectively. The RRU in inferior wall was significantly
      lower than those in the other walls. The regional clearance rate (RCR) in these
      four walls were 25.1 +/- 4.6, 22.5 +/- 8.2, 29.7 +/- 8.3, 29.3 +/- 3.4 (%),
      respectively. The RCR in inferior and lateral wall were significantly larger than
      those in anterior and septal walls. The RRU in basal, mid and apical portion were
      100.0 +/- 0, 104.5 +/- 3.3, 98.9 +/- 12.1 (%) in initial images, and 100.0 +/- 0,
      103.9 +/- 4.5, 96.8 +/- 15.2 (%) in delayed images, respectively. The RRU in mid
      portion was significantly higher than that in basal portion.(ABSTRACT TRUNCATED
      AT 250 WORDS)

PMID- 8277599
TI  - [Clinical usefulness of 111In transferrin scintigraphy in colorectal cancer].
AB  - As assessment was made regarding the clinical value of 111In transferrin in
      scintigraphy on 28 lesions in 26 cases of colorectal cancer. The positive rate of
      colorectal cancer was high: 21 lesions out of the 28 (75%) were found to be
      positive. As for the location of cancer, there was a tendency for the positive
      rate to be high in the ascending and transverse colon. There was no obvious trend
      regarding Borrmann's classification, histological type, or macroscopic depth of
      invasion. There was a trend for cases in which the maximum diameter of the tumor
      was large and depth of invasion was in progress to be positive. Ten cases in
      which a specimen was resected were all shown to be positive by scintigraphy.
      Radioactivity in the tumorous regions was 4.41 +/- 2.96 times that of the non
      tumorous regions. Moreover, tumorous tissue was strongly stained by the immuno
      histological staining with anti-Tf.receptor antibody. From the above findings, it
      was considered that 111In transferrin is clinically useful in scintigraphy, since
      it is evident that it accumulates in the tissue of colorectal cancer.

PMID- 8277600
TI  - [A phase 2 clinical study of 99mTc-MAG3 injectable a dynamic renal imaging agent-
      evaluation of its safety, effectiveness and optimal dose].
AB  - A phase 2 clinical study of 99mTc-mercapto acetyl glycylglycylglycine (99mTc
      MAG3) injectable, a new dynamic renal imaging agent, was performed in 110
      patients with renal and/or urinary disorders to evaluate the safety, efficacy and
      optimal dose of this agent. Neither adverse reactions nor abnormal laboratory
      findings due to intravenous administration of 99mTc-MAG3 were observed. The
      investigators evaluated the clinical efficacy of 99mTc-MAG3 was to be effective
      in 96 of 97 cases. Among the doses of 92.5 MBq, 185 MBq, 370 MBq and 555 MBq, the
      dose of 92.5 MBq was not large enough to provide adequate-quality blood flow
      images or reliable information for evaluation of the renal blood flow. It was
      concluded that the optimal dose range of 99mTc-MAG3 was 185-555 MBq with 370 MBq
      as the standard dose. Also, we surmise that 555 MBq is especially recommendable
      when detailed blood flow information is required. These results indicate that
      99mTc-MAG3 injectable is useful for the diagnosis of renal and urinary disorders.

PMID- 8277601
TI  - [The most suitable parameter to distinguish brain tumor using 201Tl-chloride and
      SPECT].
AB  - We performed 201Tl single photon emission CT (SPECT) studies on 62 patients with
      brain tumors prior to any therapy for the tumor. Ten lesions of open-scar and 17
      patients without brain tumor were also studied. The SPECT imaging were initiated
      5 min (early image) and 4 hours (delayed image) after injection with 74 MBq of
      201Tl-chloride. For a semi-quantitative analysis, we used the ratio of delayed
      count density to the early count density of the tumor (Td/Te), the ratio of tumor
      to normal brain tissue (Te/B(e)) on the early SPECT and the index of T/B
      ((Td/Te)/(Bd/B(e))). Delay to early ratio of 34 normal brain tissue (Bd/B(e)) was
      1.22 +/- 0.15 and tended to decrease with the age. The Td/Te ratio of meningioma
      and region of operation scar was about 0.75 which was less than that of normal
      brain tissue. In 31 patients with astrocytic tumor, Td/Te ratio was clearly
      higher in poorly differentiated tumor than in well differentiated one. The index
      of Td/Te ratio was superior to Te/B(e) or T/B ratio for differentiating brain
      tumor and grading astrocytic tumor.

PMID- 8277602
TI  - [A case of intracranial malignant melanoma with increased uptake of IMP in
      SPECT].
AB  - A patient with intracranial malignant melanoma was assessed by 123I-IMP SPECT.
      Early image, performed 30 minutes after intravenous injection of 111 MBq 123I
      IMP, demonstrated an accumulation similar to normal gray matter-defect. Delayed
      image, performed 4-hour after injection, demonstrated increased accumulation of
      123I-IMP. 123I-IMP SPECT, especially delayed scan, was valuable for qualitative
      diagnosis of intracranial malignant melanoma.

PMID- 8277603
TI  - [Study of washout rate in patients with chronic renal failure by dipyridamole
      201Tl myocardial scintigraphy--comparison with hypertrophic cardiomyopathy].
AB  - Fourteen patients with chronic renal failure (CRF) were studied by dipyridamole
      201Tl myocardial scintigraphy. In this study, patients with coronary heart
      disease were excluded by clinical findings. 201Tl SPECT was performed at 8 min
      after injection of dipyridamole (0.56 mg/kg) and at a 3-hr delayed interval, and
      washout rates (WR) were calculated. Because UCG showed left ventricular
      hypertrophy (thickness; 13 +/ 2 mm) in CRF, the WR values were compared with
      those of hypertrophic cardiomyopathy (HCM) (n = 9). In CRF, an average WR was
      54.2 +/- 6.8% and was significantly higher than that in normal (46.2 +/- 9.1%, p
      < 0.05, n = 9), though WR in HCM was significantly low (26.9 +/- 11.4%, p <
      0.01). Hematocrit value was 24.5 +/- 3.2% in CRF and was significantly lower than
      that in normal (37.8 +/- 3.6%, p < 0.001). On the other hands, hemoconcentration
      was observed in HCM (hematocrit; 44.6 +/- 3.6%, p < 0.001). WR in CRF, HCM and
      normal had significant correlation with hematocrit values (r = -0.796, p <
      0.001). These results suggest that anemia or hemoconcentration may affect
      coronary blood flow and WR, and this should be considered when diagnosing
      coronary heart disease in CRF or HCM.

PMID- 8277604
TI  - [Radioimmunoassay for the pyridinoline cross-linked carboxy-terminal telopeptide
      of type 1 collagen (1CTP)--some basic aspects of the RIA kit and clinical
      evaluation in various bone diseases].
AB  - A radioimmunoassay for circulating levels of the pyridinoline cross-linked
      carboxy-terminal telopeptide of type 1 collagen (1CTP) was developed and can be
      available as a kit on a commercial base. Using the kits, we evaluated basically
      and clinically the assay. The assayed values were reproducible and the assay can
      detect as low as 0.5 ng/ml of 1CTP. In healthy volunteers, circulating level was
      high under age 24 and over age 46. In patients with bone metastasis, serum levels
      elevated even in its early stage and correlated well with clinical status. In
      other bone diseases, such as primary hyperparathyroidism, hyperthyroidism, post
      gastrectomy, hypercalcemia of malignancy and myeloma, serum levels elevated
      according to their clinical conditions. In patients with chronic renal failure,
      serum levels were high, suggesting decrease of renal clearance of 1CTP. The
      circulating 1CTP levels seemed to reflect well clinical bone destructive status.
      A high correlation between serum 1CTP level and urinary pyridinoline (r = 0.884)
      was shown, whereas essentially no correlation was observed between bone formation
      markers such as osteocalcin and alkaline phosphatase. Thus, the measurement of
      circulating 1CTP seems to be a simple and sensitive method to monitor bone
      destruction.

PMID- 8277605
TI  - [Effect of erythromycin on mucociliary transport and clinical symptoms in
      patients with sinobronchial syndrome].
AB  - The effect of erythromycin (EM) on mucociliary transport function assessed by
      saccharin test and clinical symptoms were studied in 19 patients with
      sinobronchial syndrome (SBS). Before treatment with EM, the mean nasal clearance
      time (NCT) of SBS patients was 51.9 +/- 40.5 (SD) min, which was significantly (p
      < 0.01) longer than that of control subjects (12.4 +/- 5.3 min). After 4-week
      treatment with oral EM (600 mg/day), NCT of SBS patients significantly (p < 0.01)
      improved (29.2 +/- 34.2 min). In 11 of 19 SBS patients, bacteria from sputum
      culture disappeared after EM therapy. Frequency of cough and volume of sputum
      were significantly (p < 0.05) decreased by EM therapy. Nasal symptoms (such as
      nasal obstruction and rhinorrhea) were also significantly (p < 0.05) improved by
      EM therapy. These findings suggested that disorder of mucociliary transport
      function was present in patients with SBS, and EM therapy improved this function.
      EM clinically improved not only the lower airway symptoms, but also the nasal
      symptoms.

PMID- 8277606
TI  - [Long-term artificial ventilation by nasal intermittent positive pressure
      ventilation; 6 cases of domiciliary assisted ventilation].
AB  - Six patients with chronic respiratory failure associated with hypercapnia were
      treated with nasal intermittent positive pressure ventilation (NIPPV) at home.
      NIPPV was delivered via a custom molded nasal interface described by McDermott.
      The patients consisted of one patient with kyphoscoliosis, three with Tb-sequela,
      one with COPD, and one with neuromuscular disease. Each patient had been treated
      with oxygen therapy until assisted ventilation was initiated because of CO2
      retention. NIPPV was administered using a volume cycled flow generator set to
      deliver a minute volume such that PaCO2 was maintained between 35 and 45 Torr on
      NIPPV trial performed during wakefulness under the condition of no leakage from
      the mask. Supplementary oxygen was added so that oxygen saturation was maintained
      above 90 percent during more than 95% of nighttime NIPPV. Arterial blood gas
      tensions during daytime spontaneous breathing showed an improvement (PaCO2 68.3
      +/- 7.2 Torr, PaO2 70.4 +/- 15.5 Torr, SaO2 91.6 +/- 4.3% before treatment; PaCO2
      55.8 +/- 4.7 Torr, PaO2 87.5 +/- 16.5 Torr, SaO2 95.5 +/- 1.7% on treatment, mean
      +/- SD). The duration of NIPPV at home ranged from 2 to 24 months (11.7 +/- 6.8),
      and there was no hospitalization due to exacerbation during this period. In
      conclusion, NIPPV via a custom molded mask is simple, noninvasive, and suitable
      for the provision of long-term and domiciliary assisted ventilation.

PMID- 8277607
TI  - [Measurement of bone mineral density using dual energy X-ray absorptiometry in
      asthmatic patients receiving prednisolone therapy].
AB  - Bone mineral density (BMD) of the lumbar spine (L2-L4) was measured using dual
      energy X-ray absorptiometry (DEXA), and its relationship to total dose of
      prednisolone and duration of prednisolone therapy was studied in 57 patients with
      bronchial asthma. There was a significant negative correlation between BMD and
      total dose of prednisolone (r = -0.463, p < 0.001) and between BMD and duration
      of prednisolone treatment (r = -0.30, p < 0.05). The half-yearly percent decrease
      of BMD measured in 17 asthmatic patients was 0.83% (p < 0.01) after correction
      for age-associated decline. These findings suggest that the reduction of BMD was
      related to the total dose of prednisolone and the duration of therapy in
      asthmatics.

PMID- 8277608
TI  - [Gastric metastasis of primary lung cancer].
AB  - A 74-year-old man was admitted to Keio University Hospital because of an abnormal
      shadow in the right upper lung field on chest roentgenogram. Bronchoscopic
      examination revealed malignant cells, by which large cell carcinoma of the lung
      was diagnosed. Systemic survey for metastasis disclosed an ulcerated tumor on the
      greater curvature of the stomach. Endoscopic examination showed an elevated
      submucosal tumor suggesting submucosal metastasis of lung cancer to the stomach.
      A review of 473 autopsies of primary lung cancer at Keio University from 1958 to
      1987 showed 16 cases with gastric metastasis (3.4%). Two of 16 cases were
      detected clinically. Gastric metastases were proven in 15.6% of autopsy cases of
      large cell carcinoma of the lung. Forty-three cases of primary lung cancer with
      gastric metastasis were reported in the Japanese literature from 1965 to 1990.
      Thirteen of these cases had large cell carcinoma.

PMID- 8277609
TI  - [Studies of lymphocyte subpopulations of bronchoalveolar lavage fluid in HTLV-I
      seropositive patients with uveitis].
AB  - To determine whether HTLV-I infection is associated with uveitis, we investigated
      the bronchoalveolar lavage fluid (BALF) cells in 23 patients with uveitis. Of
      these, sarcoidosis was diagnosed in 13 patients, but could not be confirmed in
      the remaining 10 patients (non-sarcoidosis). Three of 13 patients (23.1%) with
      sarcoidosis and 7 of 10 non-sarcoidosis patients (70.0%) were HTLV-I
      seropositive. In BALF, no significant differences were observed between the HTLV
      I seropositive and seronegative patients. However, in non-sarcoidosis patients,
      total cell counts, CD3+ and CD+ HLA-DR+ cells in BALF were significantly higher
      in seropositive patients than in seronegative patients. CD3+ CD25+ cells in BALF
      were markedly increased in 3 of 7 non-sarcoidosis seronegative patients. These
      findings indicated that BALF lymphocytes in HTLV-I seropositive non-sarcoidosis
      patients were more activated than those in seronegative non-sarcoidosis patients,
      supporting the hypothesis that HTLV-I infection may be associated with uveitis.

PMID- 8277610
TI  - [Changes of peripheral airways through mechanical ventilation in acute
      respiratory failure].
AB  - To evaluate the morphologic changes in the peripheral airways associated with
      positive pressure ventilation, fine fiberoptic bronchoscopy (1.8 mm outer
      diameter) was performed in 12 patients who had no history of prior pulmonary
      failure. In 19 examinations, the main morphologic findings were paleness and
      bronchial dilatation in the peripheral airways where increased secretions,
      pigmentation and stenosis or collapse were also observed. Patients with bronchial
      dilatation had longer periods of mechanical ventilation (17 +/- 8 days) compared
      to those without dilation (10 +/- 5 days). The structural destruction in the
      peripheral airways observed in patients on prolonged positive pressure mechanical
      ventilation suggests that barotrauma may be more widespread than previously
      recognized.

PMID- 8277612
TI  - [Autopsy-proven cases of fatal saddle thromboembolism in the pulmonary artery].
AB  - In 544 autopsy cases during the period from 1984 through 1990 at National Okura
      Hospital, there were 7 cases of fatal saddle pulmonary thromboembolism (1.3%).
      Pulmonary thromboembolism was included in the differential diagnosis, but not as
      a primary consideration. Therefore, no case was diagnosed antemortem. Saddle
      thromboembolus is defined here as a thromboembolus which impacted in the main
      pulmonary artery or lodged astride the bifurcation. The cases were 5 females and
      2 males ranging in age from 53 to 76 years. During the clinical course of the
      initial disease, sudden symptoms including dyspnea, chest pain or tachypnea
      developed, and death occurred within one hour or in a relatively short period of
      time. In case 6, sudden death followed removal of a central venous catheter
      inserted in the inferior vena cava one week previously. In cases 2, 3, and 5,
      deep vein thromboemboli were detected at postmortem examination. In cases 3 and
      4, the patients were 3- and 5-days postoperative, respectively. Laboratory data
      obtained before death showed no abnormalities of hematologic and coagulation
      profiles. At autopsy, the pulmonary artery trunk was completely occluded by
      embolus, and thromboemboli were detected in the femoral and iliac veins in 3
      cases. These thromboemboli were composed of fibrin and red cells enmeshed with
      platelets. On microscopic examination, endothelial disruption was not observed at
      the levels of the large and smaller pulmonary vessels, which underlies thrombosis
      in situ or creates a procoagulant environment. Proximal pulmonary thromboemboli
      were demonstrated in only one out of seven cases (Case 1). Saddle
      thromboembolism, in our limited observation, resulted from the impact of large
      floating embolus, emanating from elsewhere, against the large pulmonary artery,
      rather than the propagation of a smaller pulmonary embolus originating in a
      peripheral artery.

PMID- 8277611
TI  - [Quantitative evaluation of gene expression of IL-1 beta and IL-1 receptor
      antagonist (IL-1ra) from alveolar macrophages in idiopathic pulmonary fibrosis
      (IPF) and sarcoidosis].
AB  - Our previous studies demonstrated the concomitant release of IL-1 and IL-1ra in
      the culture supernatants of alveolar macrophages in both healthy subjects and
      patients with interstitial lung diseases. IL-1ra was decreased in healthy smokers
      (HS), IPF, and sarcoidosis, compared to healthy nonsmokers (HNS), although an
      increase in IL-1 release could not be detected. In this study, we examined
      whether such findings could be found at the gene level, or reflect
      posttranscriptional regulation in patients with IPF (n = 8), sarcoidosis (n = 7),
      healthy smokers (n = 6) and healthy nonsmokers (n = 5). The expression of IL-1
      beta, IL-1ra and a house keeping gene (glucose 6 phosphate dehydrogenase: G6PD)
      was investigated using reverse transcription polymerase chain reaction (RT-PCR).
      After RT-PCR, analysis and quantification of PCR products were performed by high
      performance liquid chromatography. We used 26 cycle for IL-1 beta and IL-ra mRNA
      and 29 for G6PD, because amplification of mRNA was in the exponential phase on
      that cycles, respectively. The results were expressed as the ratio of each mRNA
      to G6PD mRNA. IL-1ra/G6PD ratio in patients with IPF and sarcoidosis, was lower
      than that in HNS. On the other hand, IL-1 beta/G6PD ratio was similar in all
      groups. IL-1ra/IL-1 beta ratio was decreased in patients with IPF and
      sarcoidosis, compared to HNS. These results suggest that decreased expression of
      IL-1ra gene may contribute to the development of chronic low grade inflammation
      of the lung.

PMID- 8277613
TI  - [T cell receptor heterodimer (alpha beta/gamma delta) expressions in diffuse
      panbronchiolitis].
AB  - Several reports have indicated that T cells bearing gamma delta T cell receptor
      (TCR) are major effector cells in mucosal immunity of the murine intestinal
      tract. In humans, abnormal distribution of gamma delta + T cells has also been
      found in inflammatory bowel diseases. We studied TCR heterodimer expressions in
      lymphocytes infiltrating the peripheral airways in patients with diffuse
      panbronchiolitis (DPB), because DPB is histologically characterized by chronic
      inflammation in bronchioles and could be a model for investigation of the
      significance of gamma delta + T cells in persistent inflammation of the human
      respiratory tract. Open lung biopsy specimens were obtained from 7 patients and
      peripheral blood lymphocytes (PBL) from 9 patients. Immunohistochemically, we
      detected alpha beta and gamma delta TCR by avidin-biotin complex immunoperoxidase
      method, utilizing BMA 031 and TCR delta 1 monoclonal antibody, respectively, PBL
      were analyzed by flow cytometry. Histological analysis revealed that DPB lesions
      mainly involved the bronchiolar walls with marked infiltration of small round
      cells. Many T cells were distributed in the submucosal area, although few T cells
      infiltrated the epithelium. Most of the T cells in the bronchioles expressed
      alpha beta TCR (98.7%), whereas only 1.3% expressed gamma delta TCR. There was no
      significant difference in the percentage of gamma delta + T cells in PBL between
      DPB and age- and sex-matched controls (6.7% vs. 9.1%). These results suggest that
      the increase of T cells bearing alpha beta TCR played a major role. However, the
      possibility that the decrease of T cells bearing gamma delta TCR caused reduced
      mucosal defense against external antigens, leading to persistent inflammation of
      the lower respiratory tracts in DPB, is not excluded.

PMID- 8277614
TI  - [Availability of diagnosis by percutaneous needle aspiration cytology of the lung
      in cases who showed a peripheral solitary tumorous shadow on chest Xp and
      diagnostic rate of transbronchial approach].
AB  - We report the availability of diagnosis by percutaneous needle aspiration
      cytology of the lung (NAC) in 526 cases who showed a peripheral solitary tumorous
      shadow on chest Xp. The positive rate of the transbronchial approach was 62% (147
      of 238) in lung cancer cases and 43% (6 of 14) in metastatic lung tumor cases.
      The positive rate of NAC in relation to lung cancer increased with decrease of
      diameter of the tumor. The positive rate of NAC was significantly higher than the
      positive rate of the transbronchial approach with NAC. Complications of NAC were
      bloody sputum (11%), pneumothorax (8%) and subcutaneous emphysema (0.2%), which
      did not create therapeutic problems. Pleural dissemination (0.4%) was a serious
      complication of NAC.

PMID- 8277615
TI  - [Pharyngeal cross-sectional area and pharyngeal compliance in normal Japanese
      males and females].
AB  - It is reported that obstructive sleep apnea syndrome (OSAS) has a marked elderly
      male predominance and that patients with OSAS have reduced pharyngeal cross
      sectional area and increased pharyngeal collapsibility. These reports suggest
      that the size and mechanical properties of the pharynx have sex- and age-related
      differences even in normal subjects. However, there are only a few reports on
      normal values of pharyngeal cross-sectional area and compliance. The purpose of
      this study was to determine the normal values of the pharyngeal cross-sectional
      area and compliance in Japanese healthy subjects and to determine sex-related
      differences and the effect of age, body size, and body posture on these
      parameters. We examined 181 subjects with an age range spanning 21-69 years, with
      normal range of body mass index and without enlarged tonsils or jaw retrusion. No
      subject complained of symptoms suggestive of OSAS. We measured the pharyngeal
      cross-sectional area in three body positions (sitting, lateral and supine) using
      the acoustic reflection technique (AAAR). Fifty airway area versus distance
      functions with a rate of 3 times per second were measured and averaged in each
      body position during normal breathing of room air. After identifying the fauces
      and the glottis on the averaged area versus distance function, we defined a
      region between 2 cm distal to the fauces and 2 cm proximal to the glottis as a
      pharyngeal segment and computed the mean area of that segment (mean pharyngeal
      cross-sectional area).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277617
TI  - [A case of primary amyloidosis with diffuse alveolar hemorrhage].
AB  - A 58-year-old man was admitted complaining of hemoptysis and dyspnea. Chest
      roentgenogram demonstrated bilateral alveolar infiltrates in the middle and lower
      lung fields. Diffuse alveolar filling shadows were seen on standard chest CT
      images. His symptoms and pulmonary infiltrates gradually resolved after
      administration of high-dose corticosteroids and erythromycin.
      Immunoelectrophoresis showed increased IgM of lambda type. Transbronchial lung
      biopsy specimens revealed amyloid deposits in the alveolar septa and blood vessel
      walls. Cervical lymph node biopsy specimen also showed amyloid deposits. The
      amyloid in this case stained positively with anti-A lambda type amyloid antibody.
      A diagnosis of primary systemic amyloidosis was made.

PMID- 8277616
TI  - [Effects of theophylline on ventilatory regulation in patients with chronic
      obstructive pulmonary disease].
AB  - The effects and the mechanism of single and long-term administration of
      theophylline on ventilatory regulation were investigated in patients with chronic
      obstructive pulmonary disease (COPD). The ventilatory and mouth occlusion
      pressure (P0.1) responses during CO2 rebreathing were measured before and 4 hours
      after oral, single administration of theophylline in 15 patients with pulmonary
      emphysema, 15 patients with asthma and 10 healthy subjects. Ventilatory response
      to CO2 (VE/PCO2) was increased in patients with asthma and P0.1 response to CO2
      (P0.1/PaCO2) was increased in patients with pulmonary emphysema after single
      theophylline administration. In patients with pulmonary emphysema, the increase
      in P0.1 was more marked than that in maximum inspiratory pressure static (MIPS).
      The effect of long-term administration of theophylline was studied in 8 patients
      with COPD and 8 patients with restrictive lung disease. In patients with COPD,
      P0.1/PaCO2 was significantly increased and the increase was maintained until
      three months later. These findings suggest that theophylline is effective in
      improving ventilatory and occlusion pressure responses to CO2 in patients with
      asthma probably by its bronchodilating effect, and in patients with pulmonary
      emphysema by its direct effect on the ventilatory control system.

PMID- 8277618
TI  - [A case of chronic aspiration pneumonia after total gastrectomy caused by
      gastroesophageal reflux revealed by a "modified-salivagram"].
AB  - A 76-year-old male patient suffered from recurrent bacterial pneumonia of the
      right upper lobe and both lower lobes since 2 years after total gastrectomy for
      gastric cancer. He was treated with antibiotics repeatedly without complete
      remission. Meanwhile, chronic cough, purulent sputum, and persistent bilateral
      pulmonary infiltration developed gradually. Upper digestive tract endoscopy
      showed moderate reflux esophagitis. For diagnosis, we performed upper digestive
      tract scintigraphy, a "modified-salivagram", to detect aspiration and GER.
      Although aspiration was not detected, GER reaching to the upper portion of the
      esophagus was observed 46 min after taking radio-labeled albumin, and chronic
      aspiration pneumonia with GER was thus diagnosed. Bed blocks and gragling with
      ponvidone-iodine after meals and before sleep greatly improved the symptoms of
      cough and sputum. The bilateral infiltrative shadows disappeared with resolution
      of symptoms. Chronic aspiration resulting from GER is an important cause of
      chronic airway infection. Even if a patient with reflux esophagitis is
      asymptomatic, chronic aspiration pneumonia should be suspected in cases of
      recurrent or persistent pneumonia in both lower lobes. The "modified-salivagram"
      is a sensitive test to detect aspiration and GER in hypoacidic states, such as in
      total gastrectomy and elderly patients.

PMID- 8277619
TI  - [A case of intercostal neuropathy (Th 2-9) due to sarcoidosis].
AB  - Neurosarcoidosis is a disorder which presents in 5 percent of cases of general
      sarcoidosis, in only 10% of which the peripheral nerves are involved. A patient
      who complained of numbness of the abdomen and back associated with paralytic
      motion of intestines was admitted. The patient was diagnosed as having
      neurosarcoidosis of the intercostal nerves (Th2-9) on the basis of abnormality of
      somatosensory evoked potentials (SEP) and reduced conduction velocity, and
      evident disease of intrathoracic lesions confirmed by biopsy. Corticosteroid was
      administered, with relief of symptoms and active response on SEP. Somatosensory
      evoked potentials and VC were of great value in the diagnosis and follow up of
      peripheral neuropathy due to sarcoidosis.

PMID- 8277620
TI  - [A case of minimal size small cell carcinoma arising in abnormal branching
      bronchus with mycobacteriosis].
AB  - A 73-year-old male was referred to our hospital because of mycobacteriosis.
      Bronchoscopic examination revealed a depressed lesion with white pseudomembrane
      located between the orifice of B2 and B3 of the right upper lobe. From this
      pseudomembrane, Mycobacterium avium complex was cultured, and the patient was
      treated with antituberculous drugs. Four months later, a small white polypoid
      tumor was found at the same site, growing gradually. Biopsy specimens showed
      invasion of small cell carcinoma, so we started combination therapy with anti
      cancer drugs and irradiation. With this therapy, the small polypoid tumor
      disappeared and we found the orifice of an abnormal branching bronchus between
      the orifice of B2 and B3. A case of minimal size small cell carcinoma arising at
      the orifice of an abnormal branching bronchus with mycobacteriosis was reported
      and case reports in Japan were reviewed.

PMID- 8277621
TI  - [A case of radiation pneumonitis caused by treatment of lung cancer which
      revealed marked hypervasculality on bronchial arteriography].
AB  - A 44-year-old man was admitted to our hospital because of hemoptysis. He had been
      admitted to our ward in June 1991, after resection of a brain tumor at another
      hospital due to cerebral metastasis of lung cancer (adenocarcinoma). Systemic
      chemotherapy and pulmonary irradiation therapy were performed during the first
      hospitalization. Radiation pneumonitis occurred 1 month after the completion of
      radiotherapy, which responded to administration of corticosteroids. One year and
      4 months later after the completion of radiotherapy, he was readmitted to our
      hospital because of hemoptysis. Chest computed tomogram and bronchoscopy showed
      no recurrence of lung cancer, so pulmonary arteriography and bronchial
      arteriography were performed to investigate the cause of hemoptysis. Pulmonary
      arteriograms showed diminished vascularity in the area of radiation fibrosis, but
      a bronchial arteriogram showed inflammatory hypervascularization in the same
      field. We considered that the bronchial arterial angiogenesis induced by
      radiation pneumonitis was the cause of hemoptysis. Bronchial arteriography is
      necessary in cases of radiation pulmonary fibrosis with hemoptysis without
      obvious recurrence of tumor. If the growth of new blood vessels in the bronchial
      artery can be induced by radiation therapy, the administration of anti-cancer
      agents to the bronchial artery should be considered in the treatment of recurrent
      lung cancer after radiation therapy.

PMID- 8277623
TI  - [A case of angiosarcoma of the heart with cardiac tamponade and repeated
      hemoptysis].
AB  - A 30-year-old man who died from brain metastasis of cardiac angiosarcoma is
      presented. His chest X-ray film showed cardiac tamponade and bilateral pleural
      effusion. His symptoms were improved only by drainage of the bloody pericardial
      and pleural effusion. During the course of the disease, multiple nodular
      infiltrates were seen on chest CT and hemoptysis occurred repeatedly. He
      presented to our hospital. On the first night of hospitalization, symptoms
      including headache, vomiting and disturbance of consciousness appeared and brain
      CT showed suspected brain metastasis. He died on the 20th hospital day with no
      definite diagnosis having been established. At postmortem examination, a hen's
      egg sized cardiac angiosarcoma was found infiltrating the right atrial wall.
      Metastatic foci were found in the epicardium and bilateral lungs. This case was
      considered to be angiosarcoma of the heart, manifesting various clinical symptoms
      because of bleeding from the metastatic foci.

PMID- 8277622
TI  - [Successful treatment with cisplatin-based chemotherapy and post-chemotherapy
      operation for mediastinal nonseminomatous germ cell tumor with pulmonary
      metastasis].
AB  - In October 1988, a 19-year-old man was admitted with complaint of chest pain.
      Chest X-ray film and CT scan of the chest revealed a large mediastinal mass and
      several bilateral pulmonary nodules. Serum hCG and alpha-fetoprotein levels were
      5096.0 mIU/ml (normal < 2.0) and 2176.9 ng/ml (normal < 10), respectively.
      Percutaneous needle biopsy of the mediastinal tumor disclosed an immature
      teratoma. The patient had normal testes on physical examination. CT scans of the
      brain and abdomen, and radioisotope scanning of the bones showed no abnormality.
      He was diagnosed as having a primary mediastinal nonseminomatous germ cell tumor
      (mixed cellular type) with pulmonary metastasis. On October 31, induction
      chemotherapy was started with PVB regimen: cisplatin 20 mg/m2 administered
      intravenously (i.v.) on days 1 through 5 every three week (three courses),
      vinblastine 0.15 mg/kg i.v. on days 1 and 2 every three weeks (three courses),
      and bleomycin 30 mg administered by i.v. push (starting on day 7) weekly x 9.
      Following the chemotherapy, serum alpha-fetoprotein fell to the normal range.
      Serum hCG decreased rapidly but did not reach the normal range. On January 7,
      1989, en bloc resection of the residual primary tumor was performed which
      involved partial pericardiectomy and wedge resection of the left upper lobe. Four
      residual pulmonary nodules were also removed. Histologically, the surgical
      specimen was composed of fibrous, necrotic tissue mainly and immature teratoma
      partially.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277624
TI  - [Incidence of nodal involvement of #12u nodes (lymph nodes around the upper lobe
      bronchus) in cases with right middle lobe, right lower lobe, and left lower lobe
      carcinoma].
AB  - #12u nodes are peribronchial lymph nodes around the upper lobe bronchus which
      should not be routinely dissected in cases with middle lobe carcinoma or lower
      lobe carcinoma. In this paper, #12u were examined histologically in 152 lung
      cancer cases. As a results, 14 of 152 (9.2%) had nodal diseases in #12 nodes.
      #12u nodes were involved in 3 of 30 N1 diseases (10%), and in 11 of 35 N2
      diseases (31.4%). There was a case which had no nodal involvement except for #12u
      node. And in three cases, we found only one nodal metastasis except for #12u
      nodes. If we did not dissect #12u nodes, these cases will be relapse in near
      future. Thus, for curative operation, #12u nodes should be dissected as a
      standard operation.

PMID- 8277625
TI  - [Preoperative staging in T1 and T2 lung cancers by mediastinoscopy and
      mediastinal lymph node dissection].
AB  - Between 1975 and 1992, mediastinoscopy and thoracotomy were performed on 184 T1
      and 271 T2 lung cancer cases consisting of adenocarcinoma and squamous cell
      carcinoma. Mediastinoscopy gave true negative findings in 90.8% of the T1
      patients, true positive findings in 7.6% and false negative findings in 1.6%. The
      comparable rates were 76.7%, 17.0% and 6.3% in T2 patients. The 5-year survival
      rate was 91.3% for T1N0M0 patients (n = 64) who underwent non-radical dissection
      (= NRD), and 69.4% for those (n = 70) who underwent radical dissection (= RD).
      The rate with NRD was significantly better (p < 0.006). The 5-year survival rate
      was 63.2% for T2N0M0 patients (n = 62) undergoing NRD, and 49.8% for those (n =
      72) undergoing RD, but the difference was not significantly. Distant metastasis
      was a common cause of death, whereas there were no deaths due to local recurrence
      in the T1N0M0 patients, whether NRD or RD was performed. These results support
      our opinions that preoperative mediastinoscopy and intraoperative node staging
      are sufficient for assessment of the N factor in T1 and T2 lung cancer, and that
      mediastinal node dissection should not be performed in T1N0M0 patients.

PMID- 8277626
TI  - [How extensive should lymph node dissection be done for the surgery of the left
      lung cancer?].
AB  - Mediastinal lymph node dissection for cancer of the left lung is more difficult
      than for cancer of the right lung because of the presence of aorta. Location and
      frequency of lymph node metastasis were examined for 231 left lung cancer
      patients who underwent pulmonary resection and mediastinal lymph node dissection,
      and survival rate of them was evaluated. Subaortic (# 5), paraaortic (#6),
      subcarinal (#7), tracheobronchial (#4) lymph nodes were the most frequently
      involved N 2 nodes. 5-year survival rate of the patients who had #4, #5, #6, #7,
      #8 or #9 lymph node metastasis was 20.7%. #4, #5, #6, #7, #8 and #9 should be
      dissected for the surgery of the left lung cancer.

PMID- 8277627
TI  - [Mediastinal lymph node dissection in left lung cancer].
AB  - It is usually impossible to perform a complete systemic mediastinal lymph node
      dissection in left-side pulmonary carcinomas because the aortic arch gets in the
      way. The purpose of this study was to determine if incomplete lymph node
      dissection influences late mortality. We retrospectively analyzed 222 patients
      who had complete resection of non-small-cell lung cancer, 141 on the right lung
      and 81 on the left lung. There were 155 men and 67 women. They ranged in age from
      35 to 78 years. 146 patients were in Stage I, 41, in the Stage II and 35, in the
      Stage III A, except for T3 diseases. The 5-year survival rates of left lung
      cancer were 82% and 35% in the Stage I group and the Stage II group,
      respectively. There was no difference when compared with the corresponding groups
      with right lung cancers. The 3-year survival, however, was 0% in the Stage III A
      group with left lung cancer excluding T3 diseases; this was significantly lower
      than that of right lung cancer (p < 0.01). The results recommend extended
      mediastinal lymph node dissection on the left-side squamous cell carcinoma to
      improve the survival of patients with left-side N2 diseases, when the
      tracheobronchial lymph nodes are involved.

PMID- 8277628
TI  - [Evaluation of hilar and mediastinal lymph node metastases in resected cases of
      bronchogenic carcinoma].
AB  - To establish a reasonable regional lymph node dissection as curative operation
      for lung cancer, hilar and mediastinal lymph node metastases were analyzed. From
      1982 to December, 1990, 404 patients underwent pulmonary resection with complete
      mediastinal node dissection. There were 194 adenocarcinomas, 175 squamous cell
      carcinomas, 14 large cell carcinomas, 13 small cell carcinomas and 8 others. The
      rates of hilar (N1) and mediastinal lymph node (N2) metastasis were 12.4% and
      28.9% in adenocarcinoma, 12.6% and 30.3% in squamous cell carcinoma, 14.2% and
      28.6% in large cell carcinoma and 15.4% and 30.8% in small cell carcinoma. In
      cases with adenocarcinoma, there was a close relationship between mediastinal
      metastasis and grade. No lymph node metastasis was seen in cases with tumor less
      than one cm in diameter. However, mediastinal node metastasis was found in cases
      with one cm or more in diameter of primary lesion and rates of metastasis were
      increased in proportion to tumor size. Because considerable metastases are found
      in the mediastinal lymph nodes and exact diagnosis of node metastasis before and
      during operation is difficult, complete mediastinal node dissection is still
      standard as curative resection for resectable lung cancer except lesion less than
      one cm in diameter or early hilar type squamous cell carcinoma.

PMID- 8277629
TI  - [Incidence of lymph node involvement in pN2 non-small cell lung carcinoma and
      reevaluation of the lymph node dissection method].
AB  - We reported post operative survival rate of 134 pN2 squamous cell carcinoma and
      adenocarcinoma patients in our institute, and analyzed the level of the
      mediastinal lymph node metastasis to evaluate the standard lymph node dissection
      method (R2b). Post operative survival rate showed no difference between the left
      and right lung carcinoma but it showed significant difference between the upper
      lobe and lower lobe of the both side. Compared with the upper lobe lung cancer,
      the lower lobe cancer showed higher incidence of metastasis to #7, #8 or #9 lymph
      node. It is suspected that lymph node dissection of ipsilateral #12 (U),
      contralateral hilar and #4 lymph node should be considered for the lower lobe
      cancer especially with #7 lymph node metastasis.

PMID- 8277630
TI  - [Skip metastases of the lymph nodes in bronchogenic carcinoma].
AB  - Of the 800 patients who underwent pulmonary resection and mediastinal lymph node
      dissection for lung cancer, 19.4% had skip metastases of the mediastinal nodes.
      The survival rate of this group was better than that of patients who had
      involvement of the pulmonary nodes as well as mediastinal nodes. There was a
      higher rate of skip metastases in upper lobe carcinoma than in lower lobe
      carcinoma, and lower lobe carcinoma frequently metastasized to the upper
      mediastinal nodes, especially to tracheobronchial and subcarinal nodes.

PMID- 8277631
TI  - [Clinical significance of extended mediastinal lymph node dissection on the basis
      of clinicopathological analysis of nodal involvement in bronchogenic carcinoma].
AB  - During the past 20 years, 1,064 cases of non-small cell lung cancer underwent
      resectional surgery in which all accessible mediastinal lymph nodes were
      dissected. Among 288 patients with histologically proven N2 disease, 182
      underwent complete dissection of the mediastinal lymph nodes; 77 had one-level
      and 105 had multi-level metastases. Fifteen percent of the patients having
      primary lesions with a maximal diameter between 21 and 30 mm had N2 disease.
      Nodal metastases to the lower mediastinum from upper lobe cancer (nonregional
      metastasis) were frequently observed as were metastases of lower lobe cancer to
      the upper mediastinum. In addition, there were often skip metastases to the
      nonregional parts of the mediastinum without regional nodal involvement in the
      mediastinum. Among left-lung cancer patients, the group that underwent nodal
      dissection after mobilization of the aorta by dividing the Botallo's ligament
      frequently had a verified metastatic node at the tracheo-bronchial angle (#4)
      which might not have been detected without that procedure. In addition, many N2
      and N3 diseases were detected by additional dissection through a median
      sternotomy. From the results of the present study, it appears that extensive
      mediastinal dissection should be recommended in surgery for lung cancer
      irrespective of the location and the size of the primary tumor.

PMID- 8277632
TI  - [The necessity of extended systemic dissection of the regional lymph node in
      radical operation for lung cancer].
AB  - Since 1979, 109 patients underwent bilateral mediastinal lymph node dissection
      through a median sternotomy as a routine procedure in the treatment of left lung
      cancer, because of the high possibility of contralateral mediastinal node
      involvement in cases of left lung cancer. The five-year survival rates of the
      initial 50 patients who underwent this operation from Oct. 1979 till Mar. 1988
      were 76.5% in N0 (n = 17), 69.2% in N1 (n = 13), 50.0% in N2 (n = 10) and 20.0%
      in N3 (n = 10). The five-year survival rate of 7 patients with pT1-2 N2M0 disease
      was 71.4%. This survival rate was only slightly different from that of the pT1
      2N0-1M0 group. From May 1985 till April 1993, 20 patients who had the cervical or
      the highest mediastinal lymph node involvement underwent cervical and bilateral
      mediastinal lymph node dissection through a cervical collar incision and median
      sternotomy. Two patients with the scalene node involvement (one each of right and
      left lung cancer) are surviving for five years or more after surgery. Extended
      ipsilateral mediastinal lymph node dissection (R2b) has been adopted as a routine
      procedure in the treatment of right lung cancer in our institute since 1990. The
      survival rate at forty months in 15 patients with N2 disease who underwent R2b
      operation was 51%. In 3 of these fifteen patients the anterior mediastinal lymph
      node metastases were revealed by post-operative pathological
      investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277633
TI  - [Significance of lymph nodes dissection of lung cancer treatment].
AB  - From 1950 to 1991, 1,221 lung cancer cases were treated with surgery in Tokyo
      Medical College Hospital. The 5-year survival rate was achieved in 70.1% for
      stage I, 49.5% for stage II, 17.0% for stage III A, 0% for stage III B and 8.3%
      for stage IV respectively. Considering for the survival rate with pN factor in
      753 resected cases, the 5-year survival rate of N0, N1, N2 and N3 cases was
      65.8%, 38.1%, 16.3% and 0% respectively. In these pN2 group, the 5-year survival
      rate of single mediastinal lymph node metastasis cases was 35.5%, while that of
      multiple mediastinal lymph node metastasized cases was 6.9%. The relationship
      between lymph node metastasis and DNA ploidy pattern was also discussed. The most
      of N0 cases showed diploid pattern, while N2 cases indicated aneuploid pattern. A
      mediastinal lymph node dissection of pN2 lung cancer cases may be effective to
      improve the prognosis of a kind of cases showing biologically low malignant lung
      cancer.

PMID- 8277634
TI  - [Complete transposition of the great arteries].

PMID- 8277635
TI  - [Clinical analysis of benign tumors of the lung].
AB  - Benign tumors of the lung occur in low frequency, but its differential diagnosis
      from malignant tumors such as lung cancer is important. This paper presents as
      analysis of clinical features of 26 cases operated on for benign tumor of the
      lung. Histologically there were 15 hamartomas, 8 sclerosing hemangiomas, 2
      inflammatory pseudotumors and one clear cell tumor. The roentgenographic
      appearances were well defined circumscribed solitary nodules in 17 cases (65%),
      and lobulation and spiculation in 9. Histological diagnosis of benign tumors was
      not obtained in all cases preoperatively. Minimal resection procedures were
      performed in 22 cases (85%). No postoperative complications developed.

PMID- 8277636
TI  - [Pseudocoarctation of the aorta associated with aortic valve regurgitation: a
      case report].
AB  - We reported a case of pseudocoarctation of the aorta associated with severe
      aortic regurgitation. A 63-year-old male admitted with congestive heart failure
      due to aortic regurgitation. The blood pressure was 170/60 mmHg in the right arm
      and the systolic pressure was 132 mmHg in the right leg. To and fro murmur and
      diastolic grade IV/VI blowing murmur was heard along the lower left sternal
      border. Aortogram demonstrated marked buckling of the descending aorta at the
      origin of the left subclavian artery without collateral circulation and bicuspid
      aortic valve with severe aortic regurgitation. His pressure gradient across the
      pseudocoarctation was 40 mmHg in the preoperative catheterization. We performed
      an aortic valve replacement (AVR) without further surgical treatment. The
      pressure gradient was reduced to 10 mmHg and his symptom improved after AVR.
      These results suggested that pseudocoarctation of the aorta may require no
      surgical treatment in some case associated with aortic valve regurgitation
      because of improvement of high pressure gradient across it by AVR alone.

PMID- 8277637
TI  - [A successful case of external conduit operation for tetralogy of Fallot with
      pulmonary atresia at the age of 17 months].
AB  - We report a successful case of external conduit operation in a 7.2 kg male
      infant. A 17-month-old boy was admitted because of increasing cyanosis and
      polycythemia. He had undergone classical Blalock-Taussig shunt at the age of 51
      days with the diagnosis of tetralogy of Fallot with pulmonary atresia. Cardiac
      catheterization showed stenosis of the right pulmonary artery related to the site
      of the shunt. We chose external conduit operation and correction of the right
      pulmonary artery stenosis instead of additional shunt and correction of the
      stenosis with cardiopulmonary bypass. He is in a good postoperative condition. It
      is preferable that external conduit operation is applied to similar infant cases
      from the standpoint of exercise ability, myocardial degeneration and
      postoperative arrhythmia.

PMID- 8277638
TI  - [Replacement of ascending and proximal transverse aorta for a 90-year-old female
      with aortic dissection].
AB  - Successful replacement of ascending and proximal transverse aorta for a 90-year
      old female with aortic dissection was achieved using selective cerebral perfusion
      with cold blood. The ascending aorta enlarged as a diameter of 7 cm and massive
      blood flow was recognized in the false lumen detected by CT scanning and
      echocardiography. After the core cooling by cardiopulmonary bypass (CPB), the
      branches of the aortic arch were cannulated and perfused with cold blood (16
      degrees C) for cerebral protection. The time of CPB, cardiac arrest and selective
      cerebral perfusion was 153 min, 92 min and 35 min, respectively. Post operative
      course was uneventful. She discharged from the hospital 4 weeks after the
      operation.

PMID- 8277639
TI  - [Two cases of aortoesophageal fistula due to ruptured thoracic aortic aneurysm].
AB  - Aortoesophageal fistula due to ruptured thoracic aortic aneurysm is uncommon, and
      exhibits extremely high mortality. We experienced two cases of such lesion. The
      first case showed aneurysm in the aortic arch closed with Dacron patch but
      leaving the esophageal defect. The patient died of an infection of the patch
      graft after oral feeding. The second case was demonstrated infected aneurysm of
      the descending aorta. The patient was rescued by primary operation, replacement
      of the aorta by an artificial graft and resection of the esophagus, and the
      secondary operation, reconstruction of the esophagus. We recommend resection of
      aneurysm and the esophagus as well in the aspect of lower post-operative
      infection in the graft and of the better prognosis of the lesion.

PMID- 8277640
TI  - [A case report of giant mediastinal thyroid carcinoma with SVC syndrome].
AB  - A 78-year-old man with SVC syndrome caused from compression by follicular
      carcinoma of the thyroid which extended to the mediastinum was presented. CT and
      MRI demonstrated a giant right thyroid tumor which extended to the mediastinum
      and displaced the trachea. The resection of 675 g-tumor was performed through
      median sternotomy and right collar incision without reconstruction of SVC. His
      postoperative course was complicated with recurrent nerve paralysis which had
      been gradually improved for several months. At present, he has been freed from
      SVC syndrome.

PMID- 8277641
TI  - International update: psychiatric patients in Canadian emergency departments-
      problems and trends.

PMID- 8277642
TI  - A landmark study in the use of mental health services by the mentally ill.

PMID- 8277643
TI  - Clinical depression: an ED nurse's personal experience.

PMID- 8277644
TI  - On avoiding "psych" patients.

PMID- 8277645
TI  - More on team approach to psychiatric patients.

PMID- 8277646
TI  - Attack on child by pig reported.

PMID- 8277647
TI  - A 27-year-old with a tricyclic overdose.

PMID- 8277648
TI  - Preparation, staff awareness, preventive practices, and the psychiatric patient.

PMID- 8277649
TI  - Psychiatric patients in emergency departments: Orange county, California's
      experience.

PMID- 8277650
TI  - One emergency department's guidelines for the care of suicidal patients.

PMID- 8277651
TI  - The care of psychiatric patients in the emergency department.

PMID- 8277652
TI  - "Psychiatric" or "medical"? Assessing confusion in the elderly patient.

PMID- 8277653
TI  - One emergency department's system for tracking mental status changes in
      psychiatric patients, with guidelines for the care of violent patients.

PMID- 8277654
TI  - Restraints: a sampling of current practice.

PMID- 8277655
TI  - One emergency department's Special Observation Record for documenting basic
      nursing interventions with psychosocial patients.

PMID- 8277656
TI  - Implementing an extended crisis evaluation unit in the emergency department in
      response to New Jersey screening law.

PMID- 8277657
TI  - Emergency nurses' perceptions of critical incidents and stress debriefing.
AB  - INTRODUCTION: This is a descriptive study of questionnaire responses of 682
      members of three state ENAs, with supporting interview data from 26 of those
      participants. The objective was to determine (1) the types of clinical events
      perceived as critical and (2) the usefulness of critical incident stress
      debriefings for emergency nurses. METHODS: Questionnaires asking emergency nurses
      to rate clinical incidents as critical and to respond to questions about their
      experiences with debriefings were sent to members of three state ENAs. Structured
      interviews about personal experiences with critical incidents and debriefings
      were conducted with 26 respondents. RESULTS: Emergency nurses responding to the
      questionnaire viewed the death of a child and the death of a coworker as the most
      critical of the possible events. The majority of interviewees saw an incident
      related to the death of a child as the most critical in their careers. Of the
      questionnaire respondents, 32% had participated in debriefings; 88% of those
      found them helpful in reducing critical incident stress. DISCUSSION: The findings
      suggest that managers should be alerted to the possibility of acute stress
      responses when emergency nurses experience a child's death. Education regarding
      stress and debriefings may be helpful to ED personnel.

PMID- 8277658
TI  - Regulation of prehospital nursing practice: a national survey.
AB  - INTRODUCTION: In 1988, the National Flight Nurses Association and ENA published a
      revised joint position statement advocating that registered nurses (RNs) "should
      not be required to certify as Emergency Medical Technicians (EMTs) at any level
      before assuming a nursing role in the prehospital environment." The position
      endorsed a collaborative role with emergency medical services agencies,
      regulation of prehospital nursing by state nursing agencies, and additional
      educational requirements in areas unique to prehospital emergency care. This
      study examines the existing state of affairs in the regulation of prehospital
      practice of RNs throughout the United States. METHODS: Data were obtained by
      review of written state rules and regulations pertaining to certification of
      prehospital care providers and by telephone survey of state emergency medical
      services agencies nationwide. RESULTS: All 50 (100%) of the states were
      contacted. In 44 of the 50 states (88%), no certification in prehospital nursing
      exists. As a result, most states require that RNs become EMTs at some level as a
      prerequisite for prehospital practice. Of these states, 36% (16/44) allow RN
      substitution to meet ambulance staffing requirements without additional
      certification requirements. Of these states, 61% (27/44) require RNs to complete
      the entire EMT curriculum to obtain certification, whereas 39% (17/44) allow
      challenge examinations in combination with varying other educational
      requirements. Nursing "certification" for prehospital practice exists in 12%
      (6/50) of states. DISCUSSION: As a nation, we are far from actualizing the
      recommendations stated in the ENA and National Flight Nurses Association
      position.

PMID- 8277659
TI  - Defusing verbal abuse: a program for emergency department triage nurses.

PMID- 8277660
TI  - Emergency department sexual assault assessment.

PMID- 8277661
TI  - Body parts drawing and aftercare sheet.

PMID- 8277662
TI  - Law and the emergency nurse. The problem of alcohol abuse.

PMID- 8277663
TI  - Sexual assault documentation tool.

PMID- 8277664
TI  - Documentation of nursing care for patients who have been restrained.
AB  - The care of patients who require restraints in the emergency department presents
      a challenge, not only for the amount and quality of behavioral interventions but
      also for the level of monitoring and documentation required. Special forms
      created to facilitate serial documentation of nursing care for patients who
      require restraints are designed to meet the unique needs of each emergency care
      facility.

PMID- 8277665
TI  - Evaluating adolescent suicide attempters: what emergency nurses need to know.

PMID- 8277666
TI  - Considerations in the care of the incompetent, injured patient.

PMID- 8277667
TI  - A 54-year-old man with hiccoughs.

PMID- 8277668
TI  - [Midwives' tour to Vidar hospital--an anthroposophical hospital in Jarna].

PMID- 8277669
TI  - [Multi-professional cooperation in providing nursing care to a mother following
      cesarean section].

PMID- 8277670
TI  - [Opinion on potential changes in Finnish midwifery education in the future].

PMID- 8277671
TI  - [The principle of continuous health care. An example in Heinola City Hospital].

PMID- 8277672
TI  - [The immediate and late results of vagotomy in a bleeding pyloroduodenal ulcer].
AB  - A 10-year experience with the use of vagotomy with the organ-preserving
      intervention in the treatment of patients with a bleeding pyloroduodenal ulcer
      who were treated for urgent and emergency indications is presented. The
      postoperative mortality was 8.1%. An excellent and good long-term result was
      noted in 88% of the patients, an unsatisfactory one--in 12%.

PMID- 8277673
TI  - [The treatment of acute esophagogastric hemorrhage in the portal hypertension
      syndrome in children].
AB  - Twenty-eight children were treated in the clinic for acute gastro-esophageal
      bleeding in portal hypertension syndrome. Conservative therapy has proved to be
      effective in 85.8% of cases. Endoscopic sclerotherapy was successfully used in 9
      of the 11 patients. In ineffective conservative treatment for 24-48 hrs from the
      onset of bleeding, the authors consider suturing the esophago-gastric junction
      with ligation of the gastric vein and blocking the arterial splenic blood flow as
      an operation of choice.

PMID- 8277674
TI  - [The surgeon's procedure in acute esophagogastroduodenal hemorrhage].
AB  - The results of treatment of 639 patients with acute esophagogastroduodenal
      bleeding have been analysed. There were the following causes of bleeding: in
      66.4%--ulcer disease, in 9.1%--gastric tumours, in 7.3%--erosive gastritis, in
      6.4%--portal hypertension, in 9.1%--the other. In 1.7% of patients, a cause was
      not established. Conservative treatment was performed in 59% of patients, surgery
      -in 41%. Complications developed in 24.9% of the patients, 8.6% died.

PMID- 8277675
TI  - [The immediate results of treating patients with acute early postoperative
      intestinal obstruction].
AB  - We performed 58,938 operations on the abdominal organs. Three hundred and six
      (37.8%) patients developed early postoperative acute ileus. After its operative
      elimination, 22 (7.2%) patients required performance of a reoperation. Ninety
      (29.4%) patients died. Of them in 72, death was caused by peritonitis, in 18-
      pneumonia, acute cardiovascular failure, impairement in cerebral circulation and
      pulmonary thromboembolism.

PMID- 8277676
TI  - [Prolonged decompression of the small intestine in the surgical treatment of
      acute intestinal obstruction and peritonitis].
AB  - Prolonged decompression of the small intestine was used in the complex surgical
      treatment of 85 patients with acute ileus (67) and peritonitis (18). The main
      stage of the operation included liquidation of ileus and elimination of a source
      of peritonitis. Antegrade nasogastric intubation of the intestine was performed
      in 54 patients, via gastrostomy--in 3, retrograde intubation via cecostomy--in
      15, via appendicostomy--in 4, via ileostomy--in 9. Performance of active
      transtubal sanation of the intestine by means of antiseptic solutions (53 cases)
      in combination with enterosorption (17) contributed to essential increase in the
      effectiveness of treatment.

PMID- 8277677
TI  - [The therapeutic measures in acute diffuse peritonitis].
AB  - Analysis of the observations of 431 patient with acute diffuse peritonitis is
      presented. Use of intraabdominal flowing lavage is recommended in patients with
      inflammatory phenomena against the background of moderately pronounced changes in
      microcirculation in the parietal peritoneum. The maximum clinical effect of
      hemosorption and lymphosorption was noted at the first 3 days after the operation
      in cathepsin-D activity in the blood equal to 14-17 activity units/(min.mg) and
      lymphorrhea over 700 ml/day. Lethality was 18.8%.

PMID- 8277678
TI  - [The use of laparostomy in treating diffuse suppurative peritonitis].
AB  - The results of surgical intervention with the use of laparostomy in 29 patients
      with diffuse purulent peritonitis at the terminal stage are presented. In 11
      cases, laparostomy was performed during the first operation, in 18--for
      postoperative peritonitis. At the time of operations, laser radiation,
      gastrointestinal intubation were widely used.

PMID- 8277679
TI  - [The immune protection of the gastroduodenal area after the surgical treatment of
      duodenal peptic ulcer].
AB  - The complex study of the indices of local immune and natural resistance in the
      parietal mucus of the gastroduodenal zone and general immunity in 174 patients
      with duodenal ulcer disease before and after surgical treatment was performed.
      Pronounced suppression of local immunity, presence of autoimmune processes having
      influence on its indices were noted. After the organ-preserving operations with
      an ulcer excision, the immune indices restored more rapidly than after gastric
      resection and vagotomy without an ulcer excision.

PMID- 8277680
TI  - [The use of sorption detoxification methods for the prevention of dynamic
      intestinal obstruction in peritonitis].
AB  - The effect of hemosorption on motor-evacuatory intestinal function was studied in
      169 patients with different forms of peritonitis of appendicular genesis. Early
      inclusion of hemosorption into the complex of treatment contributed to
      restoration of motor-evacuatory function of the intestine in 2-3 days, as well as
      to prevention of development of early commissural ileus.

PMID- 8277681
TI  - [Crohn's disease in emergency surgery].
AB  - The results of treatment of 28 patients with "appendicitis-like" form of the
      Crohn's disease are summarized. Diagnosis before the operation was supposed in 6
      patients. Operated on were 25 patients. All of them underwent appendectomy.
      Differential diagnosis of acute appendicitis and Crohn's disease in difficult, of
      main importance are the data of clinical investigation. In diagnosis verification
      by the data of histologic conclusion, the performance of postoperative specific
      antiinflammatory therapy is mandatory. Danger of appendectomy under such
      conditions is exaggerated. The result of treatment at the period of from 3 to 20
      years was studied in 22 patients operated on. Performance of postoperative
      treatment contributed to abatement of the disease, achievement of a satisfactory
      long-term result in all the patients.

PMID- 8277682
TI  - [The use of relaparotomy in emergency surgery].
AB  - After operative intervention in 61 of the 5704 patients, as necessity in
      performance of relaparotomy arose. Mortality after its use was 38%.

PMID- 8277683
TI  - [The diagnosis and treatment procedure in periodic disease].
AB  - The main forms of periodic disease are presented, clinical cases with the
      different forms are described. A special attention is paid to the problems of
      diagnosis and treatment in the emergency surgery of the abdominal organs is
      abdominal form of the disease.

PMID- 8277684
TI  - [The diagnosis and treatment procedure in nonopaque foreign bodies in the stomach
      and intestines].
AB  - For 10 years, 26 patients underwent treatment for complications caused by
      presence in the stomach and intestine of the foreign bodies with low radio
      opacity and echogenicity. All the patients were operated on. At operation, a
      cause of the disease was established: in 17 cases--a fish bone, in 5--a small
      chicken bone, in 1--a conifer needle, in 2--a wooden chip, in 1--a home-made
      toothpick.

PMID- 8277685
TI  - [The experimental validation of a method for the intraoperative assessment of the
      degree of severity of pancreonecrosis].
AB  - In the experiment on 35 dogs, it was established that the normal pancreas had
      constant bioimpedance parameters: ohmic resistance, polarization coefficient and
      capacitance. In development of pancreonecrosis, the capacitance increases, and
      the ohmic resistance and polarization coefficient decrease.

PMID- 8277686
TI  - [Changes in the content of lipids and biologically active substances under the
      influence of the ultraviolet irradiation of the blood in experimental
      peritonitis].
AB  - In dogs with experimental peritonitis, accumulation of toxic metabolic products
      caused impairment in lipid metabolism. With reduction in pronouncement of
      endotoxemia under the influence of ultra-violet irradiation, the blood level of
      biologically active substances decreased, the process of lipolysis was
      suppressed.

PMID- 8277687
TI  - [The work of a central district hospital in an extreme situation].

PMID- 8277688
TI  - [The choice of the method of vagotomy in treating duodenal peptic ulcer].

PMID- 8277689
TI  - [The pathogenetic problems of diffuse suppurative peritonitis].

PMID- 8277690
TI  - [The significance of immune disorders in the etiology and pathogenesis of
      nonspecific ulcerative colitis and Crohn's disease].

PMID- 8277691
TI  - [Clinical variants in the course of a postoperative bleeding stress ulcer].
AB  - The results of treatment of 13,246 patients with acute surgical disease of the
      abdominal organs have been analysed. In 48 patients, bleeding from a stress ulcer
      occurred. The symptoms of bleeding were studied. The variants of the clinical
      course of postoperative acute erosion and ulcer, such as the lightning-like,
      double-phase, single-phase ones, have been distinguished. Their predictive value
      is shown. In 89.6% of the patients, a postoperative stress ulcer developed in
      diseases of the hepatopancreatobiliary zone organs.

PMID- 8277692
TI  - [A method for the intraoperative diagnosis of cholangitis].

PMID- 8277693
TI  - [A method for preventing postoperative adhesive disease of the abdominal cavity].

PMID- 8277694
TI  - [The use of a laser in the catheterization of the subclavian vein].

PMID- 8277695
TI  - [A device for administering drugs as an aerosol in treating diseases of the
      distal rectum].

PMID- 8277696
TI  - [The modification of a surgical method in acute paraproctitis].

PMID- 8277697
TI  - [Ladd's syndrome as a cause of chronic pancreatitis].

PMID- 8277698
TI  - [Pancreatoduodenal resection in duodenal carcinoid complicated by hemorrhage].

PMID- 8277699
TI  - [Strangulated supracystic internal median hernia].

PMID- 8277700
TI  - [The surgical treatment of a strangulated Richter-Littre hernia in old and
      elderly patients].

PMID- 8277701
TI  - [Delayed respiratory depression after the cerebrospinal administration of
      morphine and clofelin].

PMID- 8277702
TI  - [The performance of endoscopic polypectomy in the polyclinic].

PMID- 8277703
TI  - [The diagnosis of a traumatic injury to the subclavian artery].

PMID- 8277704
TI  - [A case of a giant tumor of the corpus uteri simulating a retroperitoneal tumor].

PMID- 8277705
TI  - Refinements in rabbit husbandry. Second report of the BVAAWF/FRAME/RSPCA/UFAW
      Joint Working Group on Refinement. British Veterinary Association Animal Welfare
      Foundation. Fund for the Replacement of Animals in Medical Experiments. Royal
      Society for the Prevention of Cruelty to Animals. Universities Federation for
      Animal Welfare.

PMID- 8277706
TI  - The effects of group housing on the research use of the laboratory rabbit.
AB  - This project evaluated the influence of group housing on common aspects of
      research use of female laboratory rabbits (Oryctolagus cuniculus). Eight rabbits
      housed individually in conventional cages were compared to a second group of 8
      housed as a social group in a proportionately larger enclosure. The group housing
      method provided increased opportunities for exercise, social contact, and a more
      novel environment. As a function of housing style, the 2 experimental groups were
      compared on humoral and delayed hypersensitivity response, feed intake, growth
      rate, and selected physiological parameters that are considered to reflect stress
      in most species. Single and group housed rabbits did not significantly differ in
      physiological and immunological measurements, indicating that the practical
      research performance (immune response, stress level, growth rates etc.) of these
      rabbits was not significantly affected by group housing compared with the more
      traditional single housing. Analysis of group social behaviour indicated that the
      rabbits preferred small social groups, had preferences for microenvironments
      within the enclosure, and exhibited behaviours that are not possible when housed
      singly. Group housing appeared to be a successful method for enriching the
      environment of female rabbits and aspects of it should be considered in the
      approach to housing rabbits used in research.

PMID- 8277707
TI  - An enzyme-linked immunosorbent assay (ELISA) for monitoring guineapigs and
      rabbits for Bordetella bronchiseptica antibodies.
AB  - An enzyme-linked immunosorbent assay (ELISA) for monitoring antibodies specific
      to Bordetella bronchiseptica in guineapigs and rabbits was developed. In
      conventional and SPF colonies of guineapigs and rabbits, the ELISA was equally
      successful in detecting infected animals when compared to selective cultivation
      from the respiratory tract. The ELISA showed a sensitivity of 100% and a
      specificity of 90% in guineapigs. In rabbits the sensitivity and specificity of
      the ELISA were 97% and 91% respectively. In rabbit sera from infected colonies,
      ELISA activity showed a statistically significant correlation with titres
      obtained in the micro-agglutination test. Since serologically unrelated strains
      of the bacterium exist, the monitoring of animals for B. bronchiseptica infection
      by ELISA should be performed with various antigens.

PMID- 8277708
TI  - An enzyme-linked immunosorbent assay (ELISA) for monitoring rodent colonies for
      Streptobacillus moniliformis antibodies.
AB  - An enzyme-linked immunosorbent assay (ELISA) to measure Streptobacillus
      moniliformis antibodies in mice and rats was developed. Twelve S. moniliformis
      strains originating from cases of rat-bite fever and Haverhill fever in man and
      from various rodent species, showed considerable serological relationship. The
      ELISA appeared specific since antibodies to S. moniliformis were absorbed by
      autologous and homologous antigen, but not by heterologous bacterial antigens.
      Acholeplasma laidlawii showed partial serological relationship with S.
      moniliformis. The ELISA was validated using experimental infections in mice and
      rats. These studies and observations in naturally infected feral rats, confirmed
      that S. moniliformis is difficult to grow on primary isolation, and that the
      ELISA for S. moniliformis antibodies revealed more contaminated animals than
      culture.

PMID- 8277709
TI  - Mammary tumour induction by pituitary grafting in male mice: an animal model for
      male breast cancer.
AB  - Isologous anterior pituitary grafting, 4 each, to 3-4-month-old SHN and SLN male
      mice resulted in an appearance of mammary tumours from 8 months of age and the
      incidence at 12 months reached 53.8% in each strain. All tumours were diagnosed
      as type B adenocarcinomas. In association with the results, normal mammary gland
      growth and mouse mammary tumour virus (MMTV)-gp52 antigen levels in the
      submaxillary glands were stimulated by the treatment in these strains. The effect
      of pituitary grafting was much less in GR/A male mice in which no mammary tumours
      appeared.

PMID- 8277710
TI  - A simple technique for blood collection in the pig.
AB  - A simple technique for blood collection in pigs of body weight 15-40 kg is
      described. The subcutaneous abdominal vein was used for rapid collection of 5-20
      ml of blood samples. The animals were premedicated with 10 mg/kg of ketamine and
      600 micrograms of atropine given intramuscularly prior to blood collection.

PMID- 8277711
TI  - Haematological and plasma biochemical values for healthy Yucatan micropigs.
AB  - Blood samples (n = 135) were collected from 36 male and 35 female 20 +/- 4-week
      old Yucatan micropigs and were analysed for 19 haematological and 18 plasma
      biochemical parameters at weeks 20, 24, 33, 46, 59, 71 and 80. For each
      parameter, the total number of analyses per sex, mean values, standard deviation,
      lowest and highest values, and 95% confidence intervals are presented as
      reference values for this breed. Age- and sex-related differences in these
      parameters are also discussed.

PMID- 8277712
TI  - The influence of buprenorphine or bupivacaine on the post-operative effects of
      laparotomy and bile-duct ligation in rats.
AB  - The post-operative effects of laparotomy and common bile-duct ligation were
      investigated in rats. Bile-duct ligation caused a significant reduction in food
      and water consumption, body weight and locomotor activity in the immediate post
      operative period. Animals which underwent laparotomy in which bile-duct ligation
      was not carried out (sham operated groups) had significantly less depression of
      food and water consumption and body weight than groups which underwent bile-duct
      ligation. The detrimental effects on food and water consumption and body weight
      could be significantly reduced by the administration of buprenorphine (0.05
      mg/kg, s/c), but not by infiltration of the surgical wound with the long-acting
      local anaesthetic agent, bupivacaine. The reduction of the depressant effects of
      surgery on food and water consumption by the opioid analgesic buprenorphine
      suggests that some of these changes may be related to the presence of post
      operative pain.

PMID- 8277713
TI  - Illustrated guide to surgical technique for vasectomy of the common marmoset.
AB  - The surgical technique for vasectomy of the common marmoset (Callithrix jacchus)
      is described and illustrated.

PMID- 8277714
TI  - Light intensity and the oestrous cycle in albino and normally pigmented mice.
AB  - The effects of light intensity (15-20 lux & 220-290 lux) on the oestrous cycle of
      albino and normally pigmented mice were examined. The oestrous cycle of both
      types of mice was shorter at the lower intensity but the difference was
      significant only with the black mice. The proportion of albino mice from which
      embryos were recovered was significantly smaller than the proportion of black
      mice at 15-20 lux but not at 220-290 lux. No significant differences due to
      strain or light intensity were found in the number of embryos recovered. We
      conclude that pigmented mice respond in the same way as albino mice to changes in
      light intensity within the range normally found in laboratory animal
      accommodation. That is, increased light intensity prolongs the oestrous cycle and
      the period of vaginal cornification.

PMID- 8277715
TI  - Chondroma of the foreleg in a Syrian hamster.
AB  - A spontaneous bone tumour in the foreleg of a Syrian hamster was shown to be a
      chondroma; this is only the second report of such a tumour and the first
      described in detail.

PMID- 8277716
TI  - Helicobacter-associated hepatitis of mice.

PMID- 8277717
TI  - Environmental stability of rat coronaviruses (RCVs)

PMID- 8277718
TI  - Infectivity and pathogenesis of titered dosages of simian immunodeficiency virus
      experimentally inoculated into longtailed macaques (Macaca fascicularis).
AB  - The 50% macaque infectious dose (MID50) and pathogenesis of uncloned simian
      immunodeficiency virus (isolated from a pigtailed macaque, SIVmne) was determined
      in longtailed macaques (Macaca fascicularis). Five pairs of macaques were
      inoculated with 10-fold dilutions of the virus stock, and one macaque was mock
      infected. The virologic and clinical status of these macaques was monitored for
      up to 80 weeks. The MID50 of SIVmne was determined to be 10(2) cell culture
      infectious dose of the original virus stock. In order to test the infectivity and
      pathogenesis of an established viral dose, six additional macaques were
      inoculated with 10x MID50 (10(3) cell culture infectious dose) of the SIVmne. The
      virologic and clinical status of these macaques was monitored for 40 weeks. All
      of the macaques inoculated with 10x MID50 or greater became infected as evidenced
      by seroconversion and consistent virus isolation from peripheral blood
      mononuclear cells. Macaques infected with SIVmne had an initial sharp decrease in
      CD2, CD20, CD4, CD8, and CD4CD29 lymphocyte subsets, whereas the CD4:CD8 ratio
      increased. Viremic macaques developed persistent slight to moderate peripheral
      lymphadenopathy approximately 3 to 4 weeks after inoculation. Four macaques
      subsequently died of AIDS-like disease at 29, 33, 42, and 80 weeks after
      inoculation. Data obtained from the viral titration study and the acute infection
      model will aid in the development of animal trials to evaluate antiretroviral
      therapies and preventive vaccines against human immunodeficiency virus infection.

PMID- 8277719
TI  - Effects of viral and mycoplasmal infections, ammonia exposure, vitamin A
      deficiency, host age, and organism strain on adherence of Mycoplasma pulmonis in
      cultured rat tracheas.
AB  - Adherence to host cells is thought to be a pathogenetic mechanism in mycoplasmal
      diseases, thus, factors affecting adherence could affect disease expression. To
      determine whether factors that affect expression of Mycoplasma pulmonis
      respiratory disease in rats alter adherence of the organism to respiratory
      epithelium, we studied adherence of radiolabelled M. pulmonis in perfused whole
      rat tracheas. Adherence was significantly increased in tracheas from rats with
      sialodacryoadenitis virus infection or vitamin A deficiency (103 +/- 16% and 112
      +/- 29% of control means, respectively), but Sendai virus infection, ammonia
      exposure, and host age (40 versus 8 weeks) were not associated with increased
      adherence. We also assessed the relationship between adherence and virulence of
      M. pulmonis strains. The virulent strain 5782C was more adherent (51 +/- 7%) than
      the type strain, PG34(Ash), and a polystyrene-adherent, hemadsorbing UAB CT
      subclone was more adherent (229 +/- 40%) than a UAB CT subclone that does not
      adhere to polystyrene or erythrocytes. PG34(Ash) and the UAB CT subclones caused
      rhinitis only; however, the adherent UAB CT subclone caused significantly more
      severe rhinitis than either the nonadherent subclone or PG34(Ash) as determined
      by scoring of histologic sections. To determine whether M. pulmonis itself
      induces changes in respiratory epithelium resulting in enhanced adherence, we
      studied adherence in tracheas from rats inoculated with M. pulmonis 3 weeks
      earlier. Adherence was increased 64 +/- 22%, compared with that in tracheas from
      control rats. Adherence in infected tracheas treated with tetracycline for 2 days
      was not increased, indicating that M. pulmonis-induced changes in epithelial
      adherence are rapidly resolved after elimination of infection.

PMID- 8277720
TI  - Infectivity, disease patterns, and serologic profiles of reovirus serotypes 1, 2,
      and 3 in infant and weanling mice.
AB  - The oronasal median infectious doses of reovirus serotypes 1, 2, and 3 were
      established in infant and weanling Sencar mice on the basis of disease expression
      and seroconversion. Infant mice were susceptible to infection with low doses of
      all three serotypes, whereas weanling mice were comparatively resistant to
      infection. Uniform transmission of virus to cagemates or mothers of infants did
      not occur, indicating low contagiousness of all three virus serotypes. The
      comparative susceptibility of 2-day-old Sencar mice to disease was examined
      following oronasal inoculation with reovirus 1, 2, or 3. Tissues were collected
      on days 3, 5, 7, 9, 14, 16, and 21 after inoculation for virus isolation,
      histologic examination, and serologic analysis. Disease patterns in infant mice
      were distinctly different among reovirus serotypes. Reovirus 3 induced severe
      disease, with focal myocarditis, hepatitis, diffuse encephalitis, and generalized
      lymphoid depletion, whereas reovirus 1 induced a similar pattern, but much milder
      disease. In contrast, reovirus 2 induced mild transient enteritis without lesions
      in other organs. Sera from experimentally infected mice were tested in virus
      serotype-specific enzyme immunoassays. Cross reactivity of antibody among the
      three virus serotypes was found, but antibody titers were always highest with the
      homologous antigen. These studies confirm that infant laboratory mice are
      susceptible to infection with all three serotypes of virus; weanling mice are
      comparatively resistant to infection and disease; the viruses induce different
      patterns of disease in infant mice; and infecting virus serotypes can be
      distinguished serologically by enzyme immunoassay.

PMID- 8277721
TI  - Prevalence of coronavirus antibodies in rabbits.
AB  - Antibodies to coronavirus were detected by an indirect fluorescent antibody test
      in rabbit sera from six rabbitries. The prevalence ranged from 3 to 40% in
      different rabbitries and most seropositive rabbits were more than 4 months old. A
      rabbitry with high prevalence of antibodies and high incidence of diarrhea could
      serve as a source of virus and aid in studying the natural history of coronavirus
      infection in rabbits.

PMID- 8277722
TI  - Prevalence and risk factors for iron deficiency anemia in weanling rhesus
      macaques.
AB  - Standard epidemiologic methods were used to determine the prevalence and risk
      factors for iron deficiency at weaning in 143 weanling rhesus macaques (Macaca
      mulatta) raised indoors at the California Primate Research Center, Davis, CA.
      Maternal, infant, and management factors were investigated. Prevalence of iron
      deficiency anemia was 19%, as defined by mean corpuscular volume less than or
      equal to 66 femtoliters. It was found that animals raised entirely or partially
      in the nursery had less iron deficiency than dam-reared offspring. Results also
      suggest multiparous dams were more likely to have iron-deficient weanlings than
      primiparous dams. These results were discussed in relation to human and nonhuman
      primate pediatric medicine.

PMID- 8277723
TI  - Husbandry factors and the prevalence of age-related amyloidosis in mice.
AB  - A retrospective study of the prevalence of amyloidosis in mice from several
      facilities was done. Amyloid deposition is an age-related lesion. The influence
      of common laboratory factors on the occurrence of this lesion was analyzed. This
      study documented genotypic difference in susceptibility to amyloidosis and showed
      that caging and pathogen status both impact on the number of cases of amyloidosis
      seen in a population. The lowest percentage of affected mice was seen when the
      animals were individually caged in a specific pathogen-free facility where
      conditions of stress were minimized.

PMID- 8277724
TI  - A time-course study of airway hyperresponsiveness in conscious parainfluenza
      virus type 3-infected guinea pigs.
AB  - The study of virus-induced airway hyperresponsiveness may provide insight into
      mechanisms that contribute to respiratory diseases such as asthma. We examined
      changes induced by parainfluenza virus type 3 (PI-3) in lung lesions, tissue
      weights, and airway responsiveness to aerosols of histamine, methacholine, or
      citric acid in conscious guinea pigs, using modified whole body plethysmography.
      During the first week after inoculation, infected lung tissue had
      peribronchiolitis and airway hyperresponsiveness to various agents when dyspnea
      and significant respiratory events were measured; these effects persisted
      throughout postinoculation weeks 2 and 3. Airway hyperresponsiveness was defined
      by reductions in the onset of dyspnea or significant respiratory events.
      Throughout the course of the study, PI-3 infected animals had resting respiratory
      patterns that reflected labored breathing and may have been related to the edema
      indicated by increased lung weights. Furthermore, increased numbers of
      inflammatory cells were observed in lung tissue as well as bronchoalveolar lavage
      fluid of infected animals at these times. Unlike PI-3 infection, exposure to gram
      negative endotoxin resulted primarily in airway hyporesponsiveness to histamine
      aerosol. Hence, we have shown PI-3 infection in guinea pigs causes time-dependent
      alterations in airway responsiveness to diverse bronchoactive agents as well as
      in normal breathing patterns, which may persist up to several weeks after
      inoculation in animals that may otherwise appear normal.

PMID- 8277725
TI  - New experimental model of proximal and distal colon transposition in rats.
AB  - The proximal and distal portions of the colon have different morphologic and
      histochemical features. To ascertain whether these features are genetically or
      environmentally determined, we attempted to develop a transposition model of the
      proximal and distal portions of the colon in rats. Four-month-old male Fisher 344
      rats were used. Four centimeters of the proximal colon segment circulated by the
      right colonic artery and 4 cm of the distal colon segment circulated by the
      middle colic artery were interchanged isoperistaltically. In the control group,
      the colon was transected and reanastomosed. All rats tolerated the surgery and
      maintained good condition for 4 weeks, when they were euthanized. No differences
      in body weight and food intake were observed between the transposition and
      control groups. Macroscopic appearance of the stomach and small intestine was
      normal in both the transposition and control groups, but the cecum was dilated
      and the new proximal portion of the colon was slightly dilated in the
      transposition group. This new experimental model will be helpful in examining the
      mechanism by which different features of the proximal and distal portions of the
      colon are derived. It will also assist in the research of carcinogenesis in the
      colon, in determining why the distal portion of the colon is more susceptible to
      carcinogens, compared with the proximal portion of the colon.

PMID- 8277726
TI  - The effect of cage size on play and aggression between dogs in purpose-bred
      beagles.
AB  - One intent of the proposed changes to USDA 9, CFR Part 3 was to give kennel dogs
      an opportunity for exercise and play (socialization). Increasing cage size was
      proposed as a means to encourage exercise and play, thus enhancing the well-being
      of kennel dogs. Eleven-month-old, female, purpose-bred Beagles, housed four to a
      cage, were videotaped for 15 hours on 10 different dates, resulting in five
      videotapes recorded for a smaller cage size and five videotapes recorded for a
      larger cage size. A total of 40 dogs were videotaped. For each videotape,
      aggression, play, and distance between dogs were recorded and analyzed. There
      were no differences in aggression or play, but the dogs did put significantly
      more distance between themselves in the larger cage.

PMID- 8277727
TI  - DNA fingerprinting for genetic monitoring of inbred laboratory rats and mice.
AB  - DNA fingerprinting using a nonisotopically labeled minisatellite probe provided a
      valuable technique for genetic monitoring/quality control of laboratory rodents.
      Each of 12 inbred rat strains had a unique fingerprint pattern, and colonies
      separated for over 20 years had identical or nearly identical patterns. Strain
      LOU/Iap, which is known to have been genetically contaminated in the past, was
      clearly different from strain LOU/CN, supporting previous findings of studies
      using biochemical markers. Inbred strains of mice were also found to differ from
      each other. The F1 hybrid between C57BL/6 and CBA/Ca could not be distinguished
      from C57BL/6 by using DNA fingerprints, although they could be distinguished by
      using biochemical markers. Some congenic strains differed from their inbred
      partner. A suspected genetic contamination of MRL/Mp-lpr mice could not be
      detected in a sample of the breeding colony by using biochemical markers;
      however, DNA fingerprints from the suspect animals clearly demonstrated genetic
      segregation. DNA fingerprinting will be of particular value in investigating
      suspected problems as only a small sample of fresh, frozen, or ethanol-preserved
      tissue is needed. Thus, the actual suspect animals can be studied, rather than
      samples from a breeding colony from which contaminated animals may already have
      been eliminated.

PMID- 8277728
TI  - A chronic Access Port model for direct delivery of drugs into the intestine of
      conscious dogs.
AB  - Gastric physiologic properties and emptying can significantly affect the
      stability and absorption of drugs given orally. A method to deliver drugs
      directly into the intestines and peritoneal cavity in conscious dogs by using a
      modified Vascular-Access Port (VAP) was developed and validated. Modified
      silastic VAP catheters size 7 or 9 French were placed in the duodenum, jejunum,
      colon, and/or peritoneal cavity in nine adult male dogs. Catheter placement was
      validated in six dogs by using contrast radiography and by monitoring the fecal
      excretion of blood after injection of blood via the VAP directly into the
      intestines. Three dogs were successfully used to evaluate the absorption of a
      peptide that inhibits platelet aggregation. Results showed this to be a feasible,
      easily validated model for delivering drugs directly into the intestines of
      conscious dogs.

PMID- 8277729
TI  - Evaluation of butorphanol tartrate and buprenorphine hydrochloride on the
      inflammatory reaction of the Sereny Test.
AB  - Invasion of the ocular epithelia of guinea pigs by virulent Shigella organisms,
      eliciting keratoconjunctivitis, is the basis of the Sereny Test (ST). This test
      has been used to ascertain the virulence of Shigella strains and more recently to
      screen candidate Shigella vaccines for efficacy. This test undoubtedly causes
      pain in test animals; however, recommendation for use of local
      analgesics/anesthetics has not been accepted because of concern that these
      topical agents may affect the ability of the Shigella organisms to invade the
      ocular epithelia or have a physiologic effect on the inflammatory process.
      Similarly, investigators are hesitant to use systemic analgesics in conjunction
      with the ST. Two blinded studies were conducted to evaluate the effects of
      selected systemic analgesics on the ST in outbred Hartley guinea pigs. Study 1
      evaluated the recommended dosages for two systemic analgesics; study groups
      consisted of those receiving butorphanol tartrate (n = 16), those receiving
      buprenorphine hydrochloride (n = 16), and untreated controls (n = 5). Study 2
      evaluated a low-dose buprenorphine hydrochloride group (n = 16) and an untreated
      control group (n = 5). All animals were inoculated with Shigella flexneri, strain
      2a 2457T, onto the cornea and conjunctiva of each eye. At the onset of clinical
      signs, analgesics were administered to test groups. The degree of
      keratoconjunctivitis was evaluated per standard procedure; animals were weighed
      daily. After 7 days, animals were euthanatized and the eyes were removed for
      histologic morphometric evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277730
TI  - Comparison of Telazol, Telazol-ketamine, Telazol-xylazine, and Telazol-ketamine
      xylazine as chemical restraint and anesthetic induction combination in swine.
AB  - The use of Telazol (T, tiletamine and zolazepam, 4.4 mg T/kg) alone, Telazol
      ketamine (TK, 4.4 mg T/kg and 2.2 mg K/kg), Telazol-xylazine (TX, 4.4 mg T/kg,
      2.2 mg X/kg), and Telazol-ketamine-xylazine (TKX, 4.4 mg T/kg, 2.2 mg K/kg, and
      2.2 mg X/kg) as chemical restraint and anesthetic induction combination was
      compared in pigs. Forty mixed-breed healthy pigs (24.4 +/- 5.6 kg, mean +/- SD)
      were randomly assigned to the four treatment groups (T, TK, TX, TKX) with 10 pigs
      in each group. All the anesthetics were premixed by adding sterile water,
      ketamine, xylazine, or xylazine and ketamine directly into the Telazol vial and
      given as a single intramuscular injection. All four anesthetic combinations
      induced a rapid onset of sternal recumbency within 1.76 +/- 1.0 minutes and
      lateral recumbency within 3.02 +/- 2.2 minutes in pigs after intramuscular
      injection; there was no significant difference among treatments. The combinations
      TX and TKX induced analgesia (as evident by a lack of response to needle prick in
      the middle portion of the pinna and flank regions) duration of 29.0 +/- 11.0 and
      36.0 +/- 12.2 minutes, respectively, and ability to tolerate tracheal intubation
      (as evident by lack of coughing and chewing response to a laryngoscope) for a
      period of 34.0 +/- 8.4 and 39.0 +/- 9.9 minutes, respectively. The combinations T
      and TK did not induce analgesia nor conditions suitable for intubation. Duration
      of lateral recumbency was 29.9 +/- 10, 33.1 +/- 6.9, 52.2 +/- 6.9, and 61.5 +/-
      10.7 minutes in T-, TK-, TX-, and TKX-treated pigs, respectively.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8277731
TI  - Practical and effective eradication of pinworms (Syphacia muris) in rats by use
      of fenbendazole.
AB  - Oxyurid parasites are common contaminants of laboratory rodents, and despite many
      described treatments, no method has assumed preeminence. Limitations in drug
      efficacy and the general inability to control for exposure to infective eggs are
      the primary contributors to treatment failure. In addition, some effective drugs
      must be eliminated from consideration because of narrow safety margins, other
      toxic aspects, or concerns related to particular uses of the experimental
      animals. As an alternative to currently described treatments or surgical
      derivation, we conducted an efficacy study against Syphacia muris in rats with a
      new fenbendazole-based protocol. Fenbendazole is a highly efficacious broad
      spectrum anthelmintic with adulticidal, larvicidal, and ovicidal actions. Its
      pharmacokinetic behavior, ovicidal activity, and exceptionally wide safety margin
      in rats and mice make it an attractive choice for pinworm treatment. We used a
      150-ppm medicated feed formulation to reach a targeted dose of 8.0 to 12.0
      mg/kg/day in three separate studies designed to assess drug intake and efficacy
      under different housing conditions and in breeding and nonbreeding populations of
      ACI rats. In all cases, drug was given on alternating weeks, and nonbreeding
      populations were medicated for a cumulative period of 14 days. The same schedule
      was used for breeding populations, but the treatment was repeated after a 2-week
      rest period to ensure sufficient exposure for newly weaned animals. The results
      of our study indicate that our described treatment, in combination with
      environmental control measures against pinworm eggs, is capable of eliminating S.
      muris.

PMID- 8277732
TI  - A standard procedure for measuring pellet hardness of rodent diets.
AB  - A Chatillon Model TCM-200 test stand with exchangeable flat horizontal or concave
      receptacle bases and a DFI-200 gauge load cell with multiple types of upper
      exchangeable test jaws (large round-flat, medium round-flat, chisel, bullet, and
      cone-shaped) were compared by using preautoclaved and autoclaved NIH-31 rodent
      diet pellets to determine which type of hardness testing system would give the
      most accurate and reproducible results for measuring pellet hardness. The type
      and size of the contact area of the upper jaws significantly affected the force
      required to break the pellets. Significant differences were observed between the
      flat-horizontal and concave receptacle bases in the force required to break the
      pellets when using the two round-flat upper jaws. In contrast, similar results
      were obtained with both bases when the bullet, chisel, or cone-shaped upper jaws
      were used. Autoclaved pellets were 69.4% (range, 49 to 94%) harder than
      preautoclaved pellets. These results suggest that different testing systems can
      be used for measuring pellet hardness and that a standard procedure must be used
      in order to compare pellet hardness results between different testing
      laboratories. It was concluded that the flat-horizontal base and the larger round
      flat end upper jaw gave the most reproducible results for measuring pellet
      hardness.

PMID- 8277733
TI  - Diagnostic exercise: acute hemoptysis in an adult female rhesus monkey.

PMID- 8277734
TI  - Diagnostic exercise: sudden death in colony-housed rufous hummingbirds
      (Selasphorus rufus).

PMID- 8277735
TI  - Diagnostic exercise: gastritis in athymic nude mice.

PMID- 8277736
TI  - Histopathologic and immunohistochemical features of two spontaneously generated
      ocular schwannomas in Sprague Dawley rats.

PMID- 8277737
TI  - Malignant mesothelioma in an olive baboon (Papio anubis).

PMID- 8277738
TI  - Megaesophagus in a domestic ferret.

PMID- 8277739
TI  - Corynebacterium species-associated keratoconjunctivitis in aged male C57BL/6J
      mice.

PMID- 8277740
TI  - Tail gangrene in squirrel monkeys.

PMID- 8277741
TI  - Proteolytic enzyme activity in normal sheep myocardium.

PMID- 8277742
TI  - A new technique for implanting intracranial 9L tumors in rats.

PMID- 8277743
TI  - A paramedian retroperitoneal approach to the kidney and ureter in pigs.

PMID- 8277744
TI  - A reliable method for large volume blood collection in the chinchilla.

PMID- 8277745
TI  - Use of topical ivermectin treatment for Syphacia obvelata in mice.

PMID- 8277746
TI  - Determination of fatigue in the electrically stimulated quadriceps muscle and
      relative effect of ischaemia.
AB  - The creation of muscle fatigue using surface electrical stimulation represents a
      highly reproducible phenomenon in spinal cord injured patients. The torque output
      was recorded as a function of time. The fatigue curves recorded over 110s
      exhibited three main parts: first, a plateau of short duration, followed by a
      more or less steep slope and then a second plateau which was maintained for a
      long time. This phenomenon was fitted using an exponential equation which had
      been developed and four parameters introduced that outlined to the muscle
      behaviour. A set of fatigue indices was defined to characterize the asymptotic
      value, the slope, the coordinates of the inflexion point, the time constant and
      the vertical amplitude of the curve recorded. Two populations were studied; a
      group of 11 thoracic level of injury paraplegic patients and a group of 10 able
      bodied control subjects. The computed coefficients of determination, r2, were of
      very high values (0.99). Therefore, fatigue indices gave reliable information.
      Torque output did not differ between the two populations until 25 s had elapsed,
      but from 30 s onwards it was markedly lower in paraplegics. The residual torque
      output was 21.1 +/- 10.6% in the paraplegic group while it was 58.5 +/- 8.9% in
      the control group. The effect of blood supply in the production of fatigue was
      also studied by repeating the same tests using a tourniquet at the groin level.
      The residual torque became 14.7 +/- 2.3% in the paraplegic group and 42.9 +/-
      6.3% in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277747
TI  - The effect of shear forces externally applied to skin surface on underlying
      tissues.
AB  - The effects of shear forces externally applied to the skin surface on the
      underlying tissues have been investigated. An analysis of the internal stresses
      and strains was conducted using a simplified model incorporating elasticity
      theory. Skin blood flow was measured using laser Doppler flowmetry while variable
      shear forces over a range of 0-250 g were applied to the skin surface. The
      theoretical model predicts that the application of surface shear forces alters
      the internal stress distribution and makes the shear and compressive components
      of stresses increase ahead of the surface force application point. The force
      resulting from concomitant application of shear and normal force determines the
      internal maximum stress and strain. Theoretically, the shear force should have
      the same effects on the underlying tissues as normal force. The experimental
      investigations revealed that the skin blood flow decreased roughly linearly with
      the increase of shear forces. When a shear force equal to the normal force was
      applied, the flux decreased by 45%, nearly equal to the increasing magnitude
      (41%) of resultant of normal and shear forces.

PMID- 8277748
TI  - Lifespan of subcutaneous glucose sensors and their performances during dynamic
      glycaemia changes in rats.
AB  - Performances of a glucose sensor have been investigated during dynamic variations
      of plasma glucose levels. Subcutaneous glucose concentrations measured by the
      sensors were calculated by a one-point calibration, performed in basal
      conditions. A first group of sensors were chronically implanted in the
      subcutaneous tissue of normal rats. The animals were submitted to glucagon and
      insulin injection, in order to induce rapid modifications of their glycaemia.
      This test was repeated at different days after implantation in order to
      investigate the lifespan and the performance of the sensors. All the sensors were
      working 1 or 2 days after implantation, and 70% adequately responded to glycaemia
      variations at day 3 or 4. The quality of the sensors' performance remained
      constant as a function of the time. With a second group of sensors, we
      demonstrated that an efficient sterilization procedure did not alter the sensors'
      characteristics. At the day of implantation, the sterilized sensors' performance,
      during dynamic variations of plasma glucose levels, was closely similar to that
      of the non-sterilized sensors. The animals bearing the sterilized devices were
      rendered diabetic by streptozotocin (STZ) injection. Once the rats had developed
      a severe hyperglycaemia (1-3 days after STZ), they were injected with intravenous
      insulin. The subcutaneously implanted glucose sensors correctly followed the
      decline in plasma glucose levels. We therefore conclude that our sensor could
      represent a useful tool for short-term continuous blood monitoring.

PMID- 8277749
TI  - Design and evaluation of a device for measurement of interface pressure.
AB  - An electropneumatic device has been designed to measure the interface pressure
      profile under compression bandages. The device uses commercially available
      pneumatic sensors (Talley Group Ltd, SJ235/3) and measures interface pressure at
      up to eight sites simultaneously along the lower limb, with an accuracy of +/- 3
      mmHg. Measurements can be made in one of two modes: continuously at a rate of up
      to three samples per second with the results output to a suitable display device,
      or single measurements of interface pressure can be made and displayed on a
      digital display incorporated in the device. This enables the monitoring and
      recording of interface pressure under compression bandages during either
      ambulation or passive recumbency. The electropneumatic system is described
      together with its following characteristics: the hysteresis of the Talley
      pneumatic sensors, the accuracy of pressure measurement and the maximum
      achievable sample rate. Dynamic measurements in a single normal volunteer are
      shown.

PMID- 8277750
TI  - Acoustical detection of coronary occlusions using neural networks.
AB  - A nonlinear neural network classifier was applied to noninvasive acoustic
      detection of coronary artery disease; the classifier included a feature vector,
      derived from diastolic heart sounds, and a multi-layered network trained by the
      backpropagation. The feature vector is based on the linear prediction
      coefficients of the autoregressive method after an adaptive line enhancement
      method was used as the input pattern to the neural network. One hundred and
      twelve recordings (70 abnormal, 42 normal) were studied and the network was
      trained on a randomly chosen set of six abnormal and six normal patients. It was
      tested on a database consisting of 100 recordings to which it had not been
      exposed. The network correctly identified 50 of the 64 patients with coronary
      artery disease and 32 of the 36 patients without any coronary artery occlusions.
      These results showed that this neural network is capable of distinguishing normal
      patients from abnormal patients. In addition, the diagnostic capability of this
      approach is much better than any other available noninvasive approach.

PMID- 8277751
TI  - The use of strain energy as a convergence criterion in the finite element
      modelling of bone and the effect of model geometry on stress convergence.
AB  - Keyak and Skinner state that the adequacy of a finite element mesh may be
      verified by confirming that convergence of strain energy has been achieved. The
      paper concludes by stating that convergence of strain energy does not ensure that
      a particular mesh is adequate for producing accurate stress/strain results, and
      that only qualitative results can be achieved from 3D models of bone. This
      conclusion is challenged and the effect of element size on stress convergence is
      clarified. The influence of element size on stress convergence in regions of
      surface irregularity is studied and current methods are discussed that facilitate
      convergence.

PMID- 8277752
TI  - Direct and indirect methods for the quantification of leg volume: comparison
      between water displacement volumetry, the disk model method and the frustum sign
      model method, using the correlation coefficient and the limits of agreement.
AB  - Volume changes can be measured either directly by water-displacement volumetry or
      by various indirect methods in which calculation of the volume is based on
      circumference measurements. The aim of the present study was to determine the
      most appropriate indirect method for lower leg volume calculation using water
      displacement volumetry as a 'golden standard'. For 20 male volunteers, age range:
      20-35 years, the volume of both lower legs was determined directly by water
      displacement volumetry, and indirectly by the frustum sign model method and the
      disc model method. Calculation of the correlation coefficient and the limits of
      agreement showed that water-displacement volumetry and the disc model method are
      interchangeable (r = +0.99, mean +/- 2s = -45 +/- 78 ml), whereas this does not
      hold for the frustum sign model (r = +0.93, mean +/- 2s = 521 +/- 238 ml). In the
      clinical situation volume measurement can be valuable for monitoring of the
      severity of oedema or haematoma occurrence after surgery or severe trauma. This
      non-invasive diagnostic aid may be a valuable adjuvant means of diagnosis for
      several volume dependent disorders of the extremities.

PMID- 8277753
TI  - Preparation and in vivo evaluation of a newly developed bioglass ceramic.
AB  - This paper presents details of the fabrication of a glass ceramic, and its
      application as an artificial bone prosthetic material. This new bioglass ceramic,
      with composition of Na2O 8.4%, CaO 40.6%, P2O5 12% and SiO2 39%, had 160-190 MPa
      and 800-980 MPa of three-point bending strength and compressive strength
      respectively. The ceramic has a (Na, Ca) (P, Si) O3 crystalline phase with a
      uniform crystal size of about 10 microns, which was attributed to the high
      nucleation frequency. The rabbit condyle test showed that the material formed a
      tight chemical bond with biological texture and had good biocompatibility.

PMID- 8277754
TI  - The Rancho EMG analyzer: a computerized system for gait analysis.
AB  - This paper describes a computer system which accurately defines the EMG patterns
      of the lower extremities during gait. Footswitches are used to identify the
      temporal relationships and determine the phases of the gait cycle. Fine wire
      electrodes, inserted in the desired muscles of the patient being tested, provide
      EMG signals for comparison with a normal database. The system is also usable with
      surface electrodes when an appropriate normal database for surface electrodes is
      incorporated. Descriptive qualifiers (such as 'premature onset', 'delayed
      cessation', 'no clinically significant EMG', 'continuous activity' etc.) are used
      to produce a clinically relevant printed (textual) report. The intensity filtered
      average (IFA) of the EMG is shown graphically with the representative profile of
      each stride. The IFAs for all muscles tested can be plotted together (up to six
      on a page) and the graphic representation of the 'raw' EMG can be produced. The
      methods of generating the normal database by creating time-adjusted mean profiles
      (TAMP) are enumerated. The clinical use of the system is discussed. A detailed
      analysis of 31 of the most recent patient tests for which the system was used
      provides an indication of its accuracy. For 86% of the 428 muscle tests examined,
      the EMG analyser was considered to have given the correct result as compared with
      a visual analysis of the raw EMG record by a trained expert. Recommendations for
      the use and future improvements of the EMG analyser are made.

PMID- 8277755
TI  - Three dimensional shape reconstruction and finite element analysis of femur
      before and after the cementless type of total hip replacement.
AB  - Computerized tomography was used to reconstruct a shape, and stresses in three
      dimensional objects were analysed. The human femur, which has a very irregular
      shape, was chosen as an object. CT image data of a cadaver femur were transferred
      to a computer, and an edge extraction program generated the cross-section of bone
      by specifying a range of CT values for each slice. Pixel data from the CT scan
      are converted into a vector of points (x, y, z) which can specify the boundaries
      of bone. Lateral surfaces are defined by stacking up the slices and making use of
      the vectorized data. Intermediate and oblique cross-sections can be obtained by
      an interpolation technique. The constructed model was used as input data for the
      finite element analysis. To understand the stress distributions before and after
      the cementless type of total hip replacement, a three-dimensional finite element
      stress analysis of the bone-implant system was carried out, assuming micromotions
      between the stem and the femur. The analysis was done for both frictionless and
      friction cases, modelling the contact point with a gap element having isotropic
      friction. The analysis shows that the stress is not concentrated on the femoral
      calcar when the friction coefficient is large.

PMID- 8277756
TI  - Validation of an automated method of three-dimensional finite element modelling
      of bone.
AB  - This study validated an automated method of finite element modelling of bone from
      CT scan data. After a fresh-frozen cadaveric femur was modelled, strain gauges
      were attached to the bone at 11 locations and the femur was mechanically tested
      by applying a load to the femoral head. Linear regression analysis was used to
      correlate the strains predicted by the model with the experimentally measured
      strains. The regression results were significant (P < 0.001), indicating that the
      strain calculated by the FE model is a valid predictor of the measured strain.
      Verification of the surface strains also supports the validity of the strains and
      stresses predicted inside the bone. The present study provides a strong rationale
      for use of this modelling method as a research tool and in possible clinical
      applications.

PMID- 8277757
TI  - AZTDIS--a two-phase real-time ECG data compressor.
AB  - An ECG sampled at a rate of 360 samples s-1 or more produces a large amount of
      redundant data that are difficult to store and transmit; we therefore need a
      process to represent the signals with clinically acceptable fidelity and with as
      small a number of code bits as possible. In this paper, a real-time ECG data
      compression algorithm, AZTDIS, is presented. AZTDIS is an efficient algorithm
      which locates significant samples and at the same time encodes linear segments
      between them by using linear interpolation. The significant samples selected
      include, but are not limited to, the samples that have significant displacement
      from the encoded signal such that the allowed maximal error is limited to a
      constant epsilon, which is specified by the user. The way that AZTDIS computes
      the displacement of a sample from the encoded signal guarantees that the high
      activity regions are more accurately coded. The results from AZTDIS are compared
      with those from the well-known data-compression algorithm, AZTEC, which is also a
      real-time algorithm. It is found that under the same bit rate, a considerable
      improvement of root-mean-square error (RMSerr) can be achieved by employing the
      proposed AZTDIS algorithm. An average value of RMSerr of 9.715 can be achieved
      even at an average bit rate of 0.543 bits per sample by employing AZTDIS. By
      tuning the allowed maximal error of AZTDIS such that it has similar bit rate to
      AZTEC, the average value of RMSerr achieved by AZTDIS is 5.554 while the average
      value of RMSerr achieved by AZTEC under the same bit rate is 19.368.

PMID- 8277758
TI  - Comparative study of the function of the Abiomed polyurethane heart valve for use
      in left ventricular assist devices.
AB  - Hydrodynamic testing of the Abiomed polyurethane trileaflet valve has been
      carried out to establish performance data of valve function. A Medtronic Hall
      tilting disk, a Carbomedics bileaflet, a Hancock II bioprosthesis and an Abiomed
      polyurethane trileaflet valve, all size 27 mm, underwent both pulsatile and
      steady-flow hydrodynamic testing. Results of the variation of pressure difference
      with RMS pulsatile flow and steady flow, and effective orifice area, showed that
      the Abiomed valve had significantly poorer opening characteristics than the
      tissue valve and the two mechanical valves. The Abiomed valve's performance was
      seen to be related to its construction and manufacture. This study highlights
      some of the problems associated with the design and development of synthetic
      trileaflet heart valve prostheses.

PMID- 8277759
TI  - In vivo ovine flap model to evaluate surgical infection and tissue necrosis.
AB  - Although the inciting causes and the end results of soft tissue infection are
      well described, we have not achieved a quantitative methodistic description of
      the sequence of events in between. The following study presents an isolated in
      vivo model which will allow specific manipulations and quantifications of the
      events of integumentary infection. Pedicle flaps were raised on the buttock of
      the adult range ewe and it was multiply inoculated with Staphylococcus aureus,
      and followed for 96 hr. This pedicle contains not only a well-defined artery,
      vein, and nerve, but also a well-developed efferent lymphatic vessel. In
      addition, the distal portion of the flap is primarily supplied by a
      musculocutaneous arterial perforator, making the distal flap a watershed area.
      Anatomic, radiologic, and vital stain injection studies confirmed these results.
      The sheep model was found to be superior to the pig model both in terms of its
      anatomy (the addition of an efferent lymphatic vessel) as well as the disposition
      of the sheep which was more compliant than that of the pig. We believe that this
      flap will allow multiple manipulations and provide an in vivo isolated system to
      study the pathobiology of soft tissue infection.

PMID- 8277760
TI  - Glutamine does not increase ammonia in systemically drained small bowel
      transplants.
AB  - Glutamine (Gln) enhances small bowel function and ameliorates acute injury, but
      its metabolism generates portal ammonia (NH4), which normally is detoxified by
      the liver. Its beneficial use in small bowel transplantation (SBTx) therefore,
      may be offset by hyperammonemia, since such grafts may be systemically drained.
      We tested the hypothesis that oral glutamine supplementation increases plasma NH4
      in rats with systemically drained SBTx. Lewis rats with isologous SBTx had plasma
      NH4 and Gln assayed during isonitrogenous, isocaloric Gln dietary supplementation
      and were compared to controls. Plasma NH4 levels were higher in the SBTx group
      during all dietary manipulations, consistent with previous studies. A Gln
      deficient diet (0%) caused plasma Gln levels to fall in both experimental and
      control animals, but had no consistent effect on NH4 levels. With Gln
      supplementation (12.5 and 25% of total protein) Gln levels returned to baseline
      but again, plasma NH4 levels did not significantly change. We conclude that oral
      glutamine supplementation given in an isonitrogenous manner does not increase
      ammonia beyond that which is usually seen in animals with systemically drained
      SBTx. This suggests that Gln-enriched diets are not specifically contraindicated
      in patients with systemically drained SBTx and may be beneficial.

PMID- 8277761
TI  - Protection of the acutely injured heart--deleterious effects of hypothermia.
AB  - This experimental study was undertaken to evaluate the hypothesis that
      cardioplegic arrest at 37 degrees C is superior to 10 degrees C cardioplegic
      arrest in the myocardial protection of an acutely injured heart. The hypothesis
      was tested using Sprague-Dawley rat hearts that were excised and retroperfused
      with Krebs-Henseleit buffer as isolated, isovolumic heart preparations. After 15
      min of equilibration and baseline readings, ischemic injury of the myocardium was
      established by cessation of perfusion for 20 min, followed by 30 min of
      reperfusion to obtain cardiac measurements and verify uniformity of ventricular
      dysfunction. All hearts were then arrested for 30 min with continuous
      cardioplegia (oxygenated crystalloid cardioplegia, 4 ml/min) followed by 30 min
      of reperfusion. In one group (N = 12), temperature of cardioplegia was 10 degrees
      C. In the second group (N = 12), cardioplegia temperature was 37 degrees C. The
      experiments showed that in acutely injured hearts, cardioplegic arrest at 10
      degrees C resulted in further deterioration in ventricular dysfunction (P <
      0.01). In contrast, similarly injured hearts which underwent cardioplegic arrest
      at 37 degrees C showed a modest deterioration in ventricular dysfunction which
      did not reach statistical significance (P > 0.05). The experimental findings
      suggest that in the presence of acute myocardial injury, cardioplegic arrest at
      normothermia may provide better myocardial protection.

PMID- 8277762
TI  - Effect of local acid-base status on gastric mucosal blood flow and surface cell
      injury by bile acid.
AB  - Topical application of 5 mM sodium taurocholate (5 TC, pH 1.2) to canine gastric
      mucosa results in luminal hydrogen ion (H+) loss and surface epithelial cell
      (SEC) injury. However, gross mucosal injury does not occur because of a
      protective increase in gastric mucosal blood flow (GMBF). The mechanism of this
      blood flow response is unknown. To test the hypothesis that mucosal acid-base
      status influences mucosal blood flow and surface cell injury, three groups of
      dogs with vascularized chambered gastric mucosae were studied during two
      sequential 30-min periods. Mucosae were exposed during period I to topical
      acidified isotonic saline (ATS, pH 1.2), and during period II to topical 5 TC.
      During both periods, group A (n = 5) received close intraarterial (ia) NaCl (0.15
      M), group B (n = 5) close ia HCO3 (0.32 M), and group C (n = 4) close ia HCl (0.2
      N). Parameters evaluated during both ATS and 5 TC periods included the luminal
      accumulation of DNA (DNAE, a sensitive marker of SEC exfoliation), luminal H+
      loss, and GMBF measured using radiolabeled microspheres. Gastric venous pH was
      also measured. It was found that, compared to the NaCl group, the HCO3 group had
      no increase in GMBF after 5 TC exposure. Simultaneously, however, SEC loss was
      reduced by 48%, 604 +/- 72 with NaCl versus 314 +/- 59 micrograms/30 min DNA with
      HCO3, P < 0.025. Infusion of ia HCl generated a large increase in GMBF without an
      increase in SEC injury compared to ia NaCl. Thus, mucosal acid-base status is an
      important modulator of mucosal blood flow which is itself critically important to
      gastric mucosal protection during bile acid induced injury.

PMID- 8277763
TI  - Blood coagulability and hematological changes in calves with chronic centrifugal
      biventricular bypass pumps.
AB  - A Hemadyne centrifugal pump was used to determine the effects of long-term
      circulatory assist on platelet number and aggregability. Five calves were
      supported on biventricular bypass with a pair of Hemadyne centrifugal pumps. On
      the 7th postoperative day (POD), the heart was fibrillated after pump flow rates
      were increased to compensate for the total cardiac output. The animals were
      anticoagulated with heparin throughout the study and adjustments were made to
      maintain the activated clotting time at between 180 and 220 sec. To maintain the
      activated clotting time level in the therapeutic range, it was necessary to
      gradually increase the heparin dose with time due to the developing heparin
      tolerance. Fibrinogen levels increased significantly on the 3rd postoperative day
      when compared to the preoperative control value. Platelet aggregation was
      measured using a whole blood impedance method with adenosine diphosphate and
      collagen as agonists. Platelet function was found to be significantly depressed
      following the biventricular bypass procedure (P < 0.05 on the 7th, 14th, and 21st
      POD). Platelet numbers were significantly decreased compared to the preoperative
      control values, being the lowest on the 1st and 3rd POD, recovering to 76% of the
      control values by the 7th POD, and then gradually decreasing to the 55% level by
      the 28th POD. These results show that, when tested for up to 4 weeks following
      surgery, both platelet number and function in calves supported with centrifugal
      pumps remain depressed. Despite the progressive heparin tolerance and suppressed
      platelet number and function, none of the animals showed abnormal bleeding
      tendencies on biventricular bypass.

PMID- 8277764
TI  - Meniscal healing: a biomechanical study.
AB  - Insight into the functional role of menisci has stimulated investigators to
      repair meniscal tears even in regions of poor vascularity. Data on scar strength
      resulting from different forms of therapy can be obtained applying biomechanical
      methods to animal models. With our new tear load propagation test, tissue
      strength in the scar as well as in the scar periphery was determined in rabbit
      medial menisci. Standardized longitudinal lesions localized in the microvascular
      zone II near the posterior horn were left untreated, fixed by suture, or sealed
      with fibrin glue. In two consecutive trials healing was determined after 6 weeks
      and after 12 weeks. After 6 weeks the mean scar strength was 19% (no therapy),
      26% (suture), and 42.5% (fibrin glue) of the value measured in the equivalent
      region of the intact contralateral controls. In the peri-scar tissue in the line
      of the scar a section of secondary tissue weakness was discovered, which was
      shorter after treatment with fibrin glue. Although the scar strength was the same
      at Week 12, the area of tissue weakness was reduced. These biomechanical data
      point to the necessity of long-term studies to evaluate ultimate scar strength.
      They may explain the development of a bucket handle tear by extension of an
      initial lesion across an adjoining zone of secondary tissue weakness. The good
      results obtained with fibrin glue should encourage clinicians to use this therapy
      in clinical studies on meniscus repair in the inner zones of low healing
      capacity.

PMID- 8277765
TI  - Application of the popliteal lymph node assay to evaluate an immunosuppression
      protocol.
AB  - There exists a variety of experimental techniques which are used to evaluate host
      immunity. None of these in vitro assay systems are optimal, since they are
      performed ex vivo. Here is described an in vivo model, using four rat strain
      combinations and a modification of the popliteal lymph node assay, which
      quantifies the immune response to blood transfusion, in a sensitive and
      reproducible fashion. The subcutaneous injection of a 5 x 10(5) or 10 x 10(5)
      (depending on the rat strain) X-irradiated allogeneic lymph node cells into the
      hind footpad of a rat results in an increase in the weight of the draining
      popliteal lymph node harvested 7 days later. Injection of 100 x 10(5) X
      irradiated cells results in the maximum nodal enlargement (fourfold). A dose of
      50 x 10(5) cells results in lymph node enlargement just shy of maximum and so was
      selected for use in all experiments. When 50 x 10(5) nonirradiated allogeneic
      lymph node cells are injected, there is up to an eightfold increase in nodal
      size. To eliminate the effects of non-specific inflammation, as well as variation
      in node weights, a stimulation index (SI) was established. Transfusion of a
      rodent with blood from the same strain as the lymph node donor, 1 week prior to
      subcutaneous injection, resulted in a significantly lower SI, compared to the SI
      observed in untreated animals challenged with the same inoculum or third-party
      controls (P < 0.05). The significance of all comparisons was assessed by the
      Students' t test. This simple method of in vivo quantification of the immune
      response has obvious application to the evaluation of any experimental
      immunosuppression regimen.

PMID- 8277766
TI  - Free radical-induced alterations in endothelial cell function.
AB  - Free radical-induced injury to the arterial wall has been implicated in the
      pathogenesis and progression of atherosclerosis. To model the in vitro effects of
      free radicals on endothelial cell function, protein and lipid synthesis were
      measured after exposing cells to a superoxide generating system of xanthine (X =
      100 microM) and xanthine oxidase (XO = 0.2 units). Total protein synthesis,
      measured by [35S]methionine uptake, decreased by 87.65 +/- 2.04% over 4 hr
      compared to controls (P < 0.05). Examination of lipid synthesis by high
      performance liquid chromatography in cells prelabeled with either [3H]oleic acid
      or [3H]sodium acetate revealed alterations in all lipid classes. Phospholipid and
      neutral glyceride synthesis significantly decreased in a time- and dose-dependent
      fashion compared to controls (two-way ANOVA). In contrast, cholesterol synthesis
      and lipid peroxidation increased in a time- and dose-dependent fashion. When X =
      200 microM and XO = 0.3 units, there was a statistically significant increase in
      cholesterol synthesis and lipid peroxidation within 24 hr (Tukey's HSD). We
      conclude that there is evidence of endothelial cell injury as measured by
      decreases in protein, glyceride, and phospholipid synthesis. The concurrent
      increases in lipid peroxidation and cholesterol synthesis may explain the
      relationship between free radical injury and the pathogenesis of atherosclerosis.

PMID- 8277767
TI  - Lipid mediator production in acute and chronic pancreatitis in the rat.
AB  - Pancreatic production of lipid mediators of inflammation, including eicosanoids
      and platelet-activating factor (PAF), was examined in two models of pancreatitis
      in the rat. Chronic pancreatitis was induced by ligation of the pancreatic duct
      and acute pancreatitis by infusion of sodium taurocholate into the pancreatic
      duct. In the model of chronic pancreatitis, prostaglandin E2 (PGE2), PGD2, 6-keto
      PGF1 alpha, thromboxane B2 (TXB2), and PAF increased significantly in the
      pancreas in a similar fashion, whereas leukotriene B4 (LTB4) remained unchanged.
      BN52021, a PAF antagonist, reduced the accumulation of pancreatic TXB2, 6-keto
      PGF1 alpha, and PGD2, and did not affect PGE2. In the model of acute
      pancreatitis, LTB4 increased, whereas PGE2, TXB2, and 6-keto PGF1 alpha decreased
      significantly; PGD2 changed slightly; and PAF was undetectable. The present
      results indicate that mild chronic pancreatitis is accompanied by the production
      and accumulation of a wide spectrum of lipid mediators while LTB4 was the only
      lipid mediator detected at biologically active concentrations in the model of
      severe acute pancreatitis. It is suggested that various mediators are involved in
      establishing a balance between inflammation and the repair of the inflamed
      pancreatic tissue observed in mild chronic pancreatitis. While both eicosanoids
      and PAF are involved in such self-limiting responses to inflammatory challenge,
      PAF seems to play a central role in instigating the production of the various
      other mediators detected in the model of chronic pancreatitis. In the model of
      acute pancreatitis while the deficiency of various lipid mediators may render the
      pancreatic tissue more susceptible to acute damage, enhanced LTB4 appears to
      contribute to the destructive pathology observed.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8277769
TI  - Repeated dearterializations of an experimental liver tumor: short- and long-term
      results.
AB  - Intermittent dearterialization, as compared to permanent dearterialization, is
      preferably used in palliative ischemic treatment of liver tumors because
      collaterals seem to be avoidable. In this study the most efficient time period of
      hepatic arterial occlusion was assessed and short- and long-term effects of
      repeated daily dearterializations on the growth of a transplanted liver tumor was
      evaluated. In five groups of inbred Wistar/Furth rats bearing metastatic liver
      tumors the hepatic arterial circulation was repeatedly and transiently blocked
      for 0 (n = 8), 30 (n = 8), 60 (n = 8), 120 (n = 8), and 180 (n = 8) min daily for
      5 days, respectively, with an implanted minioccluder. Another group (n = 6) was
      permanently dearterialized for 5 days. In addition, one group (n = 6) was
      intermittently dearterialized 120 min/day for 18 days and compared to the no
      treatment (n = 6) and permanent dearterialization (n = 6) groups. We found that
      repeated arterial occlusions for 120 and 180 min as well as permanent
      dearterialization for 5 days almost retarded the liver tumor growth completely.
      Collaterals developed in all rats subjected to permanent dearterialization and in
      one of the rats that were dearterialized repeatedly for 180 min. However,
      prolonged intermittent dearterializations for 180 days significantly delayed the
      tumor growth compared to permanent dearterialization (P < 0.05) yet collaterals
      did not develop. Therefore, we conclude that repeated arterial occlusions for 120
      min are the optimal method of dearterialization that effectively retards the
      growth and prevents collateral circulation of this liver tumor. It may have
      implications in the palliative treatment of human liver tumor when
      dearterialization is considered.

PMID- 8277768
TI  - Role of free radical scavengers in the management of refractory duodenal
      ulceration. A new approach.
AB  - This prospective randomized double blind study examined the influence of free
      radical scavengers on the healing and recurrence of refractory duodenal
      ulceration. To this end, allopurinol (50 mg, four times a day) -a hydroxyl
      radical scavenger and an inhibitor of xanthine oxidase, the enzyme which forms
      superoxide radicals--and dimethyl sulfoxide (DMSO, 500 mg, four times a day)--a
      hydroxyl radical scavenger--were administered orally. Three hundred and sixty
      three consecutive patients with duodenal ulceration that did not heal despite 3
      months of treatment with cimetidine, who were cigarette smokers and social
      drinkers, were randomized to receive 800 mg cimetidine twice a day alone or with
      either allopurinol or DMSO. In 315 patients who were evaluable for efficacy
      analysis, the healing rate at 8 weeks was, for cimetidine alone, 60%; for
      cimetidine with DMSO, 100%; and for cimetidine with allopurinol, 100%. The
      healing efficacy of cimetidine was therefore significantly (P < 0.01) heightened
      by DMSO and allopurinol. The patients whose ulcers healed were instituted on
      maintenance treatment for 1 year and received 800 mg cimetidine at bedtime alone
      or with either DMSO or allopurinol. In 218 patients who were evaluable for
      efficacy analysis, the cumulative relapse rate at 1 year was, for cimetidine
      alone, 29%; for cimetidine with DMSO, 8%; and for cimetidine with allopurinol, 7%
      DMSO with cimetidine and allopurinol with cimetidine were, therefore, superior to
      cimetidine alone (P < 0.01) in preventing ulcer relapse. The results suggest that
      oxygen-derived free radicals are implicated in the mechanism of refractory
      duodenal ulceration and that scavenging these radicals stimulates healing and
      reduces recurrence of the ulceration.

PMID- 8277770
TI  - Comparison of Staphylococcus aureus and Escherichia coli infusion in conscious
      rats.
AB  - The purpose of this study was to compare the pathophysiology of bacteremia
      produced by intravenous infusion of either a Gram-positive (Staphylococcus
      aureus) or a Gram-negative (Escherichia coli) organism. Conscious, unrestrained,
      instrumented rats received S. aureus, E. coli, or sterile saline over 120 min,
      followed by a 240-min monitoring period. The infusates produced 90% (S. aureus,)
      80% (E. coli), and 0% (saline) mortality at 24 hr. Neither bacterial group
      produced hypotension during the entire 360-min study period. E. coli produced
      early tachycardia and increased glucose, followed by decreased stroke volume and
      increased lactate and pO2. S. aureus caused early tachycardia followed by
      decreased pH, stroke volume, and cardiac output and increased lactate and
      systemic vascular resistance. Respiration rate and central venous pressure were
      not affected by either bacterial infusion. Compared to E. coli, S. aureus
      produced decreased pH, glucose, pO2, heart rate, and cardiac output and increased
      lactate, hematocrit, pCO2, and systemic vascular resistance. These data document
      quantitative differences in the acute response of the conscious rat to bacteremia
      caused by these isolates of E. coli and S. aureus.

PMID- 8277771
TI  - Efficacy of tolmetin sodium for adhesion prevention in rabbit and rat models.
AB  - Tolmetin sodium's efficacy in preventing primary adhesions was evaluated in two
      adhesion models each in two species: (1) rabbit uterine horn, (2) rat uterine
      horn, (3) rabbit peritoneal side wall, and (4) rat peritoneal side wall. In each
      model a single instillation of tolmetin sodium solution into the peritoneal
      cavity at the time of surgery effectively reduced adhesion formation. This
      efficacy extended over a wide range of concentrations, volumes, and total
      dosages, and was similar in rabbits and rats. An aqueous solution of 1 mg/ml
      tolmetin sodium in 5-15 ml in rabbits and in 3 ml in rats was consistently
      efficacious in reducing postoperative adhesion formation.

PMID- 8277772
TI  - Effect of epidural blockade and oxygen therapy on changes in subcutaneous oxygen
      tension after abdominal surgery.
AB  - The effect of oxygen therapy (37% by face mask) and epidural local anesthetic
      blockade (9 ml 0.5% bupivacaine at Th9-11 level) on wound oxygenation was
      evaluated in eight otherwise healthy patients undergoing elective colorectal
      resection. The patients were monitored continuously for subcutaneous oxygen
      tension, arterial oxygen saturation, heart rate, and skin temperature on the day
      after operation, and arterial blood for gas analysis was drawn every 15 min
      during the study. A fluid challenge (10 ml saline/kg body wt) did not alter any
      of the measured values. The epidural blockade did not change any of the measured
      values. Oxygen therapy before epidural blockade increased median subcutaneous
      oxygen tension from 60 to 71 mmHg (P < 0.02) and, after epidural blockade, from
      64 to 71 mmHg (P < 0.02) Time to reach steady state in subcutaneous oxygen
      tension with oxygen therapy was 30 (15-55) min without epidural blockade and 15
      (10-20) min with blockade (P < 0.03). In conclusion, epidural local anesthetic
      blockade did not increase subcutaneous oxygen tension with or without oxygen
      therapy after elective uncomplicated major abdominal surgery.

PMID- 8277773
TI  - The effect of hypofibrinogenemia and fibrinolysis on skeletal muscle function
      after ischemia and reperfusion.
AB  - Isometric contraction to direct supramaximal tetanic stimulation of the anterior
      tibialis (AT) muscle was measured in 50 New Zealand White rabbits after ischemia
      and reperfusion. Ischemia was produced unilaterally by collateral ligation and
      temporary inflow control until AT muscle function decreased to < 5% of
      contralateral (control) AT muscle and the ischemic interval was recorded.
      Reperfusion was carried out in one of the following ways: group I (n = 20),
      release of vascular clamps (blood reperfusion [BR]); group II (n = 10), release
      of vascular clamps and simultaneous intraarterial administration of 50,000 units
      of urokinase (urokinase reperfusion [UR]); group III (n = 10), release of
      vascular clamps and simultaneous administration of 50,000 units of urokinase and
      28 mg (5 units) of purified rabbit plasminogen (urokinase plasminogen reperfusion
      [UPR]); and group IV (n = 10), animals defibrinated to < 50 mg/dl with ancrod
      prior to ischemia and received BR (ancrod blood reperfusion [ABR]). During
      reperfusion, function was recorded every 60 min for 2 hr. Recovery of
      experimental muscle function is expressed as the percentage of contralateral
      control limb function. The mean ischemic interval (mean +/- SEM), to achieve < 5%
      of contralateral control limb function, was 206.7 +/- 9.9, 209.5 +/- 16.6, 221.7
      +/- 12.5, and 272.0 +/- 14.2 min for animals in groups I-IV, respectively. The
      mean experimental muscle function (mean +/- SEM) following the ischemic interval
      was 3.2 +/- 0.8, 4.5 +/- 1.4, 4.4 +/- 1.2, and 3.3 +/- 1.0 for groups I-IV,
      respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277774
TI  - Interleukin-8 suppresses the toxicity and antitumor effect of interleukin-2.
AB  - The clinical application of interleukin-2 (IL-2) for the treatment of certain
      human malignancies has shown promise. However, the use of IL-2 in
      immunotherapeutic protocols has been limited due to its associated toxicities.
      The administration of therapeutic doses of IL-2 results in a vascular leak
      syndrome with associated multiple system organ edema, hypotension, and
      respiratory, renal, and hepatic dysfunction. Previous studies suggest that the
      mechanism of these toxicities involves the activation of both immune effector
      cells and the microvascular endothelium with resultant leukocyte-vessel wall
      interaction, endothelial cell injury, and subsequent invasion of normal tissues
      by activated leukocytes. Recently it has been demonstrated that interleukin-8 (IL
      8) will inhibit leukocyte adherence to an activated endothelium. Thus, we
      hypothesized that IL-8 would ameliorate IL-2-evoked detrimental effects. We also
      investigated the influence of IL-8 on IL-2-induced antitumor efficacy. Four
      groups of nontumored, female, C57BL/6 mice and four groups of C57BL/6 mice with
      pulmonary metastases from a 3-methylcholanthrene-induced fibrosarcoma (MCA-105)
      were treated every 6 hr for 4 days by intraperitoneal injections of IL-2 alone,
      IL-2 and IL-8, IL-8 alone, or an equal volume of saline which served as our
      control. Upon completion of therapy, we found that IL-8 suppressed many of the IL
      2-induced effects including multiple organ edema, hepatic dysfunction,
      leukopenia, and lymphocytic infiltration of normal organs. When the number of
      pulmonary metastases were counted 20 days after the cessation of therapy. IL-8
      was also found to significantly ablate the IL-2-elicited antitumor
      efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277775
TI  - Direct contractile effect of motilin on isolated smooth muscle cells from human
      gallbladder.
AB  - To test the hypothesis that motilin receptors are present on smooth muscle cells
      of the human gallbladder, smooth muscle cells were isolated from the gallbladder
      and their direct contractile responses to motilin were examined. Motilin elicited
      a dose-dependent contraction of human gallbladder smooth muscle cells. Maximal
      contraction rate as defined by the percentage decrease in cell length was 23.7 +/
      0.7% at 10(-7) M for motilin and was similar to that for cholecystokinin
      octapeptide (CCK-OP) (24.2 +/- 1.5%) observed at 10(-10) M. The contractile
      sensitivity of gallbladder muscle cells to motilin (ED50 = 6 pM) was two orders
      of magnitude less than that to CCK-OP (ED50 = 0.07 pM). The motilin-induced
      contraction was inhibited in a dose-dependent manner by addition of 8-(N,N
      diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride, an inhibitor of
      intracellular Ca2+ release. These results indicate that distinct motilin
      receptors are likely to be present on human gallbladder smooth muscle cells, as
      evidenced by their direct contractile responses, and suggest that Ca2+ release
      from intracellular calcium stores is important in the contractile response to
      motilin.

PMID- 8277776
TI  - Studies of human granulocyte phagocytosis stimulation by tuftsin.
AB  - Tuftsin (Thr-Lys-Pro-Arg), a natural immunomodulating peptide originally found to
      stimulate phagocytosis by polymorphonuclear leukocytes (PMNs), is now known to
      bind to both PMNs and monocyte-macrophages, affecting their phagocytosis and
      other functions. The potential roles of tuftsin in surgery-related infections
      have been documented using animal models. However, there have been some
      difficulties in demonstrating the phagocytosis-stimulating activity of tuftsin.
      In view of this, we have developed a suitable human PMN phagocytosis assay for
      tuftsin and performed preliminary kinetic studies. The assay was performed on 24
      well plates between PMNs and fluorescent microspheres. The greatest effect of
      tuftsin over the control was observed under the following conditions: 15 min
      incubation at 37 degrees C with 5 micrograms/ml tuftsin and a 50:1 ratio of
      particle to PMN. Particles bound on the surface of PMNs were removed by washing
      and trypsin treatment, followed by centrifugation through fetal bovine serum.
      This allowed us to utilize flow cytometry in this study. A flow cytometric
      procedure was then successfully adapted to human PMN phagocytosis that
      established a high correlation between microscopic evaluation and flow cytometry
      of phagocytosis. In addition to the above determinations of the percentage of
      phagocytic cells, we evaluated the effect of tuftsin on the number of particles
      engulfed by PMNs. Under the above optimum conditions, tuftsin has greater impact
      on the number of particles engulfed than on the percentage of phagocytic cells.

PMID- 8277777
TI  - A compiled BASIC program for analysis of spatial point patterns: application to
      retinal studies.
AB  - The pattern of distribution of a population of cells is of considerable interest
      to biologists and neurobiologists. However, the labor involved in collecting and
      analyzing the data often requires a significant amount of time. This paper
      presents a compiled BASIC program written using the Microsoft QuickBasic compiler
      for Apple Macintosh to facilitate such studies. The program allows collection and
      analysis of data that can be introduced either with the aid of a digitizing
      tablet of directly imported as x,y coordinates from different sources as, for
      example, word processors or image analysis software. Subsequently the program
      provides a quick, easy and interactive way of access to statistical, mathematical
      and graphical techniques used in the analysis of spatial point patterns. These
      techniques include several measures of dispersion (quadrat count, nearest
      neighbor and a 2-dimensional point autocorrelogram analysis) and arrangement.
      Although the program has been tested on spatial organization of retinal cells, it
      can be used to study the distribution of other cells in the nervous system and
      for different projects, as for example the distribution of microtubules and
      neurofilaments inside the axons. This software is available from the authors.

PMID- 8277778
TI  - Algorithms for detection and measurement of spontaneous events.
AB  - The development of the personal computer and its mass storage capabilities has
      enabled long-term digitization of voltage records at high sampling rates. This
      paper presents a program that employs algorithms to analyze a sampled record for
      spontaneously occurring events. A detection algorithm employs amplitude and
      temporal parameters to identify the onsets of these events. Other algorithms then
      characterize size and shape features of these events. Examples of the results of
      these algorithms are given for intracellularly recorded excitatory postsynaptic
      potentials (EPSPs). These algorithms permit rapid and accurate quantitation of
      tens of thousands of events that may occur over many minutes. It is suggested
      that this set of algorithms may be applied to biological events other than
      synaptic potentials.

PMID- 8277779
TI  - Fabrication of microscalpels by electrolysis of tungsten wire in a meniscus.
AB  - A simple technique has been devised for generating consistent microscalpel blades
      from tungsten wire for use in microdissections. Electrolysis of the tungsten wire
      held horizontally in contact with the extended, up-lifted meniscus of an aqueous
      solution of 1.0 N NaOH sculps the metal into a blade configuration with a very
      sharp cutting edge. These microscalpels are suitable for dissection of embryonic
      neural tissues.

PMID- 8277780
TI  - Quantifying periodic activity in central pattern generators: the crayfish
      swimmeret.
AB  - Experimental recordings from neurons are generally difficult to quantify. Spike
      patterns and membrane potential cycles are often compared qualitatively and are
      hence limited by human resolution and judgement. This paper describes a
      statistical method for quantifying individual spike patterns and membrane
      potential fluctuations in oscillating systems, allowing quantification of
      successive 'individual' bursts. The neuronal activities of the network can
      therefore be subject to more extensive analyses and comparisons. Principal
      component analysis was used to extract the principal components from a sequence
      of bursts recorded in vitro from the crayfish (Pacifasticus leniusculus)
      swimmeret. The principal component coefficients were correlated with intuitive
      biological concepts such as burst displacement, number of spikes in a burst, and
      burst width. The bursting of both interneurones and motor neurones were found to
      be modulated by some unidentified oscillator that displaced the bursts in time.
      The amplitude of the time displacements was significant, i.e., of the order of
      the bursting period (1.5 s), and the period of the oscillation was approximately
      200 bursts. The strength of the method is that this feature was detected without
      any prior suspicion of its existence.

PMID- 8277781
TI  - A rapid and sensitive radioimmunohistochemical assay for quantitation of
      vasopressin in discrete brain regions with an anatomical resolution.
AB  - Radioimmunoassay has become a widely used method to study different neuroactive
      substances from brain tissue extracts, but cannot provide anatomical resolution.
      Here we describe a simple and sensitive radioimmunohistochemical assay (RIHA) to
      quantify a peptide, vasopressin (VP), in discrete brain regions of rats with 3
      day water deprivation. After decapitation, brains were removed, frozen with dry
      ice and cut into 14-microns cryostat sections which were then fixed with 4%
      paraformaldehyde in phosphate-buffered saline. After rinses, tissue sections were
      stored in a freezer until use. For RIHA, brain tissue sections were pre
      incubated, and then incubated with rabbit vasopressin antibody (1:2000 dilution)
      for 24 h at room temperature. After rinses, sections were incubated with 125I
      labeled goat antirabbit IgG (1:200 dilution) for 1 h. Specimens were processed
      for quantitative autoradiography after rinses and drying. RIHA with aid of a
      computer-assisted image analysis system revealed that the VP content was
      significantly reduced in the paraventricular hypothalamic nucleus (PVN) and
      supraoptic nucleus (SON) of rats with 3-day water deprivation, whereas a parallel
      in situ hybridization study further demonstrated that VP mRNAs in the PVN and SON
      were greatly increased. In summary, this experiment demonstrates that RIHA is a
      simple and powerful tool which is able to detect changes of VP in the
      hypothalamus of dehydrated rats. Combining this method with in situ hybridization
      to assess mRNA expression allows assessment of the functional significance of the
      peptide changes. In this case, dehydration depletes vasopressin and upregulates
      its synthesis. Therefore, the combined use of RIHA and in situ hybridization
      should have general applicability to evaluate the functional role of a peptide or
      neurotransmitter system in response to stimuli in a quantitative way with
      anatomical resolution.

PMID- 8277782
TI  - The effect of changes in temperature and humidity on the accuracy of von Frey
      hairs.
AB  - A series of von Frey hairs was subjected to changes in temperature and relative
      humidity (RH) simulating those encountered on a neonatal intensive care unit. The
      effect of each environmental change on their calibrated value was monitored. It
      was found that changes in RH significantly affected their calibration, whereas
      changes in temperature had a smaller effect. The results of the study indicate
      that the environmental conditions in which von Frey hairs are used should be
      taken into account.

PMID- 8277783
TI  - Problems and solutions in vector control.

PMID- 8277784
TI  - Outpatient management of dengue infection in the University Hospital, Kuala
      Lumpur.

PMID- 8277785
TI  - Problems in diagnosis and classification of dengue virus infection.

PMID- 8277786
TI  - Management of dengue haemorrhagic fever/dengue shock syndrome.

PMID- 8277787
TI  - Dengue situation in Malaysia.

PMID- 8277788
TI  - Critical care aspects of dengue haemorrhagic fever/dengue shock syndrome.

PMID- 8277789
TI  - Clinical correlates with immunopathogenesis in dengue haemorrhagic fever/dengue
      shock syndrome.

PMID- 8277790
TI  - The distribution of immunoregulatory cells in the peripheral blood of normal
      Malaysian adults.
AB  - The distribution of immunoregulatory cells in the peripheral blood of an
      individual has now been established as an important tool in helping the
      management of several diseases. It is necessary to set the normal ranges of these
      cells for the laboratory. We have undertaken in this study to establish the
      reference ranges for normal Malaysian adults. We found that the mean percentages
      of T cells, B cells, T Helper cells (CD4), T suppressor cells (CD8), NK cells and
      the ratio of CD4/CD8 were 70.91%, 11.38%, 38.15%, 37.76%, 17.45%, and 1.00
      respectively. There was no significant difference between the sexes. In certain
      parameters, there was significant differences between Malay, Chinese and Indians.
      The Chinese and Indians were significantly different in the distribution of B
      cells and in the CD4/CD8 ratio. In the case of CD4 and NK cells, the Indians were
      different from the other two groups.

PMID- 8277791
TI  - Fine needle aspiration cytology of the breast: an analysis of 1,094 aspirates.
AB  - Our experience with 1,094 consecutive fine needle aspirations (FNAs) of the
      breast in 918 cases is presented. Correlation between the FNA cytology and
      subsequent histology of the lesions was available in 211 cases. FNA had a
      sensitivity rate of 87.3%, a specificity rate of 99.3% and a positive predictive
      value of 98.2%. A false negative diagnosis rate of 5.1% occurred. The overall
      diagnostic accuracy rate was 95.7%.

PMID- 8277792
TI  - Hydatidiform molar pregnancy in Malaysian women: a histopathological study from
      the University Hospital, Kuala Lumpur.
AB  - A review of gestational trophoblastic disease diagnosed at the Department of
      Pathology, University Hospital, Kuala Lumpur from January 1989 to December 1990
      using established histological criteria showed 25 complete hydatidiform moles
      (CHM), 11 partial hydatidiform moles (PHM), 1 invasive mole and 2
      choriocarcinoma. The ages of the patients with CHM ranged from 21 to 43 years
      (mean = 28.5 years) and PHM 20 to 33 years (mean = 27.5 years). The invasive mole
      occurred in a 42-year-old Malay woman. The two patients with choriocarcinoma were
      both Chinese and 41 and 46-years old respectively. During the same period, 1,062
      non-molar abortions and 13,115 births, inclusive of livebirths and stillbirths
      were recorded at the University Hospital. The incidence rate of hydatidiform
      moles was thus estimated to be 1:384 pregnancies. PHM constituted 30% of all
      molar pregnancies. Hydatidiform moles occurred among the Malays, Chinese and
      Indians at the rate of 2.43, 2.66 and 3.29 per 1,000 pregnancies respectively. It
      appears that hydatidiform molar pregnancy has the highest prevalence among the
      Indians, a finding similar to an earlier Singapore study.

PMID- 8277793
TI  - A comparative study of the in-vitro activity of cefepime and other
      cephalosporins.
AB  - Cefepime is a new cephalosporin antibiotic which is highly active against both
      Gram-positive and Gram-negative organisms. The purpose of this study was to
      establish the in-vitro activity of cefepime and three other cephalosporins
      against recent clinical isolates from patients at the General Hospital Kuala
      Lumpur. A total of 334 strains comprising Enterobacteriaceae, non-fermentative
      Gram-negative bacilli and Staphylococcus aureus were tested for their sensitivity
      to cefepime, cefotaxime, ceftriaxone and ceftazidime. Minimum inhibitory
      concentrations of the antibiotics were established using an agar dilution method.
      With the exception of some strains of Flavobacterium meningosepticum, Xanthomonas
      maltophilia and other non-fermentative Gram-negative bacilli, cefepime was found
      to be active against a wide range of Gram-negative organisms. Cefepime was as or
      more active than the other cephalosporins against Acinetobacter,
      Enterobacteriaceae and methicillin-sensitive Staphylococcus aureus. Strains of
      Klebsiella and Salmonella that were resistant to the third generation
      cephalosporins were sensitive to cefepime. Cefepime could be a valuable
      alternative for the treatment of nosocomial infections due to multiply resistant
      organisms.

PMID- 8277794
TI  - Preliminary evaluation of the INDX DIP-S-TICKS with positive rickettsial samples
      in Malaysia.
AB  - Forty-four serum samples of various reactivities to rickettsial antigens
      demonstrated by the indirect immunoperoxidase technique were tested with INDX Dip
      S-Ticks (INDX Integrated Diagnostics Inc., USA) Kit for the detection of tick
      borne diseases. The kit utilised Rickettsia rickettsii the causative agent of
      Rocky Mountain spotted fever (RMSF) as antigens. The samples positive for endemic
      typhus were also tested against R. typhi, the agent for endemic typhus by the
      same method. The aim of this study was to determine the extent of cross
      reactivity of R. rickettsii with rickettsial infections in Malaysia. Nine out of
      12 tick typhus, 4 out of 10 scrub typhus and 4 out of 12 endemic typhus samples
      cross reacted with R. rickettsii. Ten out of 12 endemic samples were positive
      with R. typhi by the same method. From the study, we concluded that the INDX Dip
      S-Ticks Kit can be used as a rapid screening test to detect endemic and tick
      borne rickettsial infections in Malaysia but a second serological test is
      strongly recommended on all weakly reactive cases.

PMID- 8277795
TI  - An in-house enzyme-linked immunoabsorbant assay for human growth hormone.
AB  - A simple, non-isotopic in-house enzyme-linked immunoabsorbant assay (ELISA) for
      human growth hormone (GH) was developed. The assay involved using in-house
      polyclonal anti-GH adsorbed onto 96-well microtitre plates, commercially prepared
      mouse monoclonal anti-GH, and goat anti-mouse IgG horseradish peroxidase
      detection system. Results of recovery and parallelism studies ranged from 95%
      106% and 98%-101% respectively, of the expected values. The detection limit of
      the assay was 0.008 mIU/well or the equivalent to 0.4 mIU/L of undiluted serum.
      Intra- and interassay coefficients of variations were 4.8%-7.9% and 6.5%-8.7%
      respectively. Serum GH levels measured in this assay correlated well with those
      measured in established in-house radioimmunoassays (r = 0.985, p < 0.001) and
      immunoradiometric assay from NETRIA (r = 0.984, p < 0.001).

PMID- 8277796
TI  - Antibody to hepatitis C virus in thalassemia patients.
AB  - A specific enzyme immunoassay (EIA) for the diagnosis of hepatitis C virus (HCV)
      infection was developed by recombinant DNA technology. Abbott HCV EIA was used to
      detect antibody to HCV (anti-HCV) in non-transfused and multiply-transfused
      thalassemia patients. None of 11 non-transfused patients had anti-HCV but 3 of 52
      (5.8%) multiply-transfused patients had anti-HCV. This study showed that the
      prevalence rate of HCV infection is low in thalassemia patients. However, it is
      still important to identify hepatitis C virus infected patients in high risk
      groups because hepatitis C is associated with chronic hepatitis, cirrhosis and
      hepatocellular carcinoma.

PMID- 8277797
TI  - Rapid dengue diagnosis and interpretation.

PMID- 8277798
TI  - Utilization of a specialized clinic following an ecological accident.
AB  - On August 23, 1988, a fire broke out in a warehouse storing PCBs, forcing the
      evacuation of 5,500 citizens. Three days later, a specialized clinic was opened
      to examine and reassure the population. Seventy percent of the evacuated people
      showed up at the clinic. The aim of this case-control study was to identify the
      determinants of utilization of this clinic among the evacuated population. Cases
      and controls were sampled from the cohort of the evacuated adults. Both cases and
      controls were randomly selected among those who consulted and those who did not
      consult at the clinic. A logistic regression identified nine predictors of
      utilization: age, family type of household, annual income less than $40,000,
      objective and perceived exposure to the toxic smoke, reaction to the risk,
      perceived scale of the evacuation, number of moves during the evacuation period
      and consultation elsewhere with a physician. Results showed that the fear
      resulting from exposure created a stronger motive to consult the clinic than
      physical symptoms and needs.

PMID- 8277799
TI  - Characteristics of patients with major depression who received care in general
      medical and specialty mental health settings.
AB  - The purpose of this analysis was to compare depressed patients receiving care in
      the general medical setting with depressed patients receiving care in specialty
      mental health settings. The analysis was limited to 559 respondents from the NIMH
      Epidemiologic Catchment Area (ECA) study who met criteria for the diagnosis of
      major depression sometime in the year before the interview as defined by the
      Diagnostic Interview Schedule. Patients who received care in the general medical
      sector were more likely to be black, older than age 65, have a high school
      education or less, and to be women, and less likely to be in the highest
      socioeconomic quartile. A higher proportion of specialty mental health patients
      reported a lifetime history of delusions, met criteria for the diagnosis of panic
      disorder, obsessive-compulsive disorder, or schizophrenia, and had a lifetime
      history of psychiatric hospitalization. Depressed patients seen in the general
      medical sector had a lower chance of meeting criteria for major depression one
      year later than those seen in the specialty mental health sector. A multivariate
      analysis limited to an investigation of the relative importance of
      sociodemographic factors indicated that the following factors were significantly
      associated with receiving care in the specialty mental health care sector: age
      groups 31-50 and 51-65, and single marital status. Black race was inversely
      correlated with use of specialty mental health care. These results suggest that
      data generated from the specialty mental health sector can be generalized to the
      general medical sector only after assessing demographic differences between the
      two groups. Demographic differences could be associated with differences in
      knowledge, attitudes, interpretation of symptoms, and treatment preferences
      related to depression.

PMID- 8277800
TI  - An examination of the Resource-Based Relative Value Scale cross-specialty linkage
      method.
AB  - The Resource-Based Relative Value Scale (RBRVS) was developed by surveying panels
      of physicians from single specialties, then merging the specialty-specific
      results into a common work scale. The merging process involved two steps: 1)
      specification of links or equivalent services across specialties: and 2) use of
      links to align work values from each specialty onto a common scale. This study
      examines the sensitivity of physician relative values of work (RVWs) to changes
      in both the specification of links and in the method for aligning specialties.
      Using the same survey data employed in developing the RBRVS, we calculated new
      RVWs based on an alternative specification of links and an alternative method for
      aligning specialties. Total RVWs declined by almost 50% for anesthesiology, and
      increased by more than 20% for allergists, neurologists, and thoracic surgeons.
      Most of this change was attributable to our specification of links. We conclude
      that future use of the linkage procedure employed in developing the RBRVS is not
      warranted without further research. Instead, efforts to update and revise work
      values could be based on a common scale of work developed by cross-specialty
      panels, thus eliminating the need for a linkage procedure.

PMID- 8277801
TI  - The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality,
      scaling assumptions, and reliability across diverse patient groups.
AB  - The widespread use of standardized health surveys is predicated on the largely
      untested assumption that scales constructed from those surveys will satisfy
      minimum psychometric requirements across diverse population groups. Data from the
      Medical Outcomes Study (MOS) were used to evaluate data completeness and quality,
      test scaling assumptions, and estimate internal-consistency reliability for the
      eight scales constructed from the MOS SF-36 Health Survey. Analyses were
      conducted among 3,445 patients and were replicated across 24 subgroups differing
      in sociodemographic characteristics, diagnosis, and disease severity. For each
      scale, item-completion rates were high across all groups (88% to 95%), but tended
      to be somewhat lower among the elderly, those with less than a high school
      education, and those in poverty. On average, surveys were complete enough to
      compute scales scores for more than 96% of the sample. Across patient groups, all
      scales passed tests for item-internal consistency (97% passed) and item
      discriminant validity (92% passed). Reliability coefficients ranged from a low of
      0.65 to a high of 0.94 across scales (median = 0.85) and varied somewhat across
      patient subgroups. Floor effects were negligible except for the two role
      disability scales. Noteworthy ceiling effects were observed for both role
      disability scales and the social functioning scale. These findings support the
      use of the SF-36 survey across the diverse populations studied and identify
      population groups in which use of standardized health status measures may or may
      not be problematic.

PMID- 8277802
TI  - Breaking with tradition: the new groups in professional nursing.
AB  - Chronic shortages of registered nurses (RNs) have stimulated interest in locating
      non-traditional sources of RNs. A statewide survey of 2,315 newly graduated RNs
      compared three non-traditional groups in nursing with their traditional
      counterparts, identifying differences that have implications for successful
      recruitment and retention. Second career nurses, former LPNs and minorities
      comprised 41.9% of the population. Compared to the traditional groups, more
      second career nurses, former LPNs and some minority groups were older, married
      and had children. Second career vs. first career nurses placed less emphasis on
      selecting schools at the highest levels of academic quality, holding out for the
      most lucrative jobs or working with the most "interesting" patients (i.e., the
      acutely ill). Former LPNs, compared to other RNs, placed greater value on easy
      access to schools and jobs. Compared to whites, minority RNs were more inclined
      to value nursing's socioeconomic rewards. However, compared to non-Asian
      minorities in nursing, Asian RNs had higher expectations for professional
      advancement and were less altruistic. Our results indicate that several of the
      new groups view nursing less as a "calling," finding the field appealing for
      practical socioeconomic reasons and accessibility.

PMID- 8277803
TI  - Bias in the coding of hospital discharge data and its implications for quality
      assessment.

PMID- 8277804
TI  - The APHA Medical Care Section proposal for a national health plan.

PMID- 8277805
TI  - ACCOR: instrumentation and database for cross-language study of coarticulation.
AB  - An unavoidable problem in speech technology, particularly in the development of
      robust automatic speech recognition systems, is the extreme variability in the
      acoustic attributes of segments. Segments are highly sensitive to context and
      bear little resemblance to their intrinsic characteristics manifested when they
      are uttered in isolation. However, the problem can become tractable if we model
      the linguistic and physiological aspects of coarticulatory processes, the main
      source of systemic variability at the segmental level.

PMID- 8277806
TI  - Coarticulation and phonology.
AB  - Many sound patterns in languages are cases of fossilized coarticulation, that is,
      synchronic or phonetic contextual variation became diachronic or phonological
      variation via sound change. An examination of languages' phonologies can
      therefore yield insights into the mechanisms of coarticulation. In this paper I
      discuss (a) the need to differentiate between phonological processes that are and
      are not due to coarticulation, (b) the need to differentiate between 'on-line'
      synchronic variation and comparable fossilized diachronic variation, (c) how to
      determine some of the constraints on coarticulation--especially the higher
      priority of maintaining acoustic-auditory, rather than articulatory, norms for
      the shape of speech elements, and (d) how coarticulation presents a "parsing"
      problem to the listener and, of course, to systems for automatic speech
      recognition.

PMID- 8277807
TI  - Coordination and coarticulation in speech production.
AB  - In this article, we consider the concepts of coordination and coarticulation in
      speech production in the context of a task-dynamic model. Coordination reflects
      the transient establishment of constrained relationships among articulators that
      jointly produce linguistically significant actions of the vocal tract--that is
      phonetic gestures--in a flexible, context-sensitive manner. We ascribe the need
      for these constraints in part to the requirement of coarticulatory overlap in
      speech production. Coarticulation reflects temporally staggered activation of
      coordinative constraints for different phonetic gestures. We suggest that the
      anticipatory coarticulatory field for a gesture is more limited than look-ahead
      models have suggested, consistent with the idea that anticipatory coarticulation
      is the onset of activation of coordinative constraints for a forthcoming gesture.
      Finally, we ascribe much of the context-sensitivity in the anticipatory or
      carryover fields of a gesture (variation due to "coarticulation resistance") to
      low-level (below the speech plan) interactions among the coordinative constraints
      for temporally overlapping gestures.

PMID- 8277808
TI  - The interplay between prosodic structure and coarticulation.
AB  - In this paper we draw on a linguistic model of prosodic structure and a task
      dynamic model of speech gestures to account for the interplay of coarticulation
      and stress in English. We reinterpret results from two experiments in which
      articulator movements were recorded for utterances varying in pitch accept
      placement. In the first experiment, jaw kinematics were studied in post-nuclear
      unaccented and nuclear accented [pap] syllables. The kinematic patterns suggested
      that gestures in syllables with greater stress (nuclear accented) show less
      coarticulatory overlap. By contrast, the vowel's low jaw target is undershot in
      unaccented syllables. Two hypotheses are possible. Either the jaw is lower in
      stressed syllables so more energy can radiate from the mouth ("sonority
      expansion") or the jaw is lower to help distinguish the low vowel from other
      vowels ("hyperarticulation"). Another experiment differentiates the two
      hypotheses by examining tongue point positions in [put] preceding a [th]. In the
      more stressed syllables, the tongue dorsum retracts more, likely to make a more
      distinct back vowel. Also, the amount of assimilation of the alveolar stop to the
      following dental is reduced. Both results suggest hyperarticulation rather than
      sonority expansion. Thus, it seems that coarticulation is reduced in stressed
      syllables, because stressed syllables are hyperarticulated.

PMID- 8277809
TI  - An electropalatographic study of alveolar and palatal consonants in Catalan and
      Italian.
AB  - Electropalatographic data for Catalan and Italian reported in this paper reveal
      the existence of two categories of palatal consonants, namely, alveolopalatals
      ([n], [lambda]) and palatals proper ([j]). All these consonants are produced with
      a single place of articulation and thus are not good candidates for complex
      segments involving a tongue front articulator and a tongue dorsum articulator. A
      higher degree of coupling between the primary articulator and other tongue
      regions for alveolopalatals and palatals than for alveolar [n] accounts for a
      reduced sensitivity to coarticulatory effects for the former vs. the latter.
      Alveolar-palatal correlations reported in this study support the notion of
      relative independence between different tongue articulators for non-dorsal vs.
      dorsal consonants. Differences in articulation and coarticulation were found for
      Italian vs. Catalan. In comparison with their Catalan counterparts, Italian shows
      the following properties: Consonants are more anterior, [n] allows less
      coarticulation at the alveolar zone (in line with the laminal nature of the
      consonant), and long alveolopalatals exhibit more contact and less coarticulation
      at the front palatal zone.

PMID- 8277810
TI  - A comparative investigation of coarticulation in fricatives:
      electropalatographic, electromagnetic, and acoustic data.
AB  - The principal aim of this investigation was to compare coarticulatory effects at
      different levels of the speech production system, in order to gain insight into
      the relations between the different levels. To this end, the relative magnitudes
      of carryover and anticipatory coarticulation with adjacent vowels were measured
      at the midpoints of the two lingual fricatives /s/ and /integral of/ in two
      speakers each of English, French, and German. Linguopalatal contact patterns
      derived from electropalatographic recordings were compared with an analysis of
      the acoustic output. The results indicated, firstly, that mismatches between
      articulatory and acoustic results are not uncommon. Secondly, and more
      surprisingly, while there was no difference in the overall magnitude of
      coarticulatory effects for /s/ and /integral of/, not all speakers showed a
      predominance of the same coarticulatory direction on both fricatives; this
      complicated the observed tendency for the predominance of carryover
      coarticulation to be greater in German and English than in French. Two speakers
      were retested using comparative analyses of electropalatography and
      electromagnetic articulography. These two procedures gave a closely parallel
      picture of lingual coarticulatory regularities (while complementing each other in
      terms of characterizing articulation). The implications of these results for
      identifying language-specific coarticulatory regularities are discussed.

PMID- 8277811
TI  - Anticipatory consonant-to-vowel coarticulation in the production of VCV sequences
      in Italian.
AB  - The study of the spatio-temporal interactions between contiguous segments in
      speech is a means for a better understanding of how segments are serially
      organized. This research explores the relation between a vowel and the following
      consonant by studying the anticipatory C-to-V coarticulatory effects by means of
      electropalatography. The materials were 'VCV utterances produced in isolation and
      in connected speech by three Italian speakers, with /a/ and /i/ as vowels and the
      coronals /t, d, l, z, integral of/ as intervocalic consonants. The results show
      that the consonants affect both the vocal tract configuration of the preceding
      vowel and its acoustic duration. The spatial effects increase from laterals to
      stops to fricatives. The tongue body position is raised during /a/ and lowered
      during /i/. The effects are much larger for /a/ than for /i/ and larger in
      connected speech than in isolated words. As for temporal coarticulatory effects,
      the data indicate that vowels tend to be shorter before /integral of/ than before
      /z/, and shorter before /t/ than before /d/ than before /l/. Spatial and temporal
      measurements of change in tongue body contact from vowel to the consonantal
      closure/constriction suggest that the consonants differ among each other in the
      dynamics as well as in the timing of their gestures, with ampler/longer movements
      (e.g., for /integral of/) starting earlier than smaller/shorter movements (e.g.,
      for /d/ or /l/). These patterns result in smaller differences between the
      durations of the total VC sequences than between the individual durations of V or
      C segments, and suggest that intersegmental organization between vowels and
      following consonants may have the rhythmic function of reducing the variability
      of vowel-to-vowel temporal intervals.

PMID- 8277812
TI  - Contextual variation of the vowel voice source as a function of adjacent
      consonants.
AB  - The contextual effects of voiced/voiceless stops on the voice source of an
      adjacent vowel were examined for the first vowel in 'CVCV utterances in German,
      English, Swedish, French, and Italian. The principal analysis technique involved
      interactive inverse filtering and parameterisation of the glottal waveform in
      terms of a four-parameter voice source model (the LF-model). This analysis
      procedure was supplemented by measures from narrow-band spectral sections of the
      speech output and by oral airflow recordings which allow inferences about the
      relative timing of glottal and supraglottal gestures. Results indicated that the
      voiced/voiceless nature of the consonant does yield differences in the voice
      source of the vowel. The most striking effects were found in the context of
      voiceless consonants, and cross-language differences did emerge in terms of
      directionality and degree. Extensive anticipatory effects were found for Swedish
      and for some speakers of English. Preceding the voiceless stop the vowel becomes
      increasingly breathy-voiced, and it would appear that the glottal abduction
      gesture is anticipated very early in the course of the vowel. Italian exhibited a
      similar tendency, though to a considerably lesser degree. The German data, on the
      other hand, showed certain strong carryover effects: Following the voiceless
      aspirated stop there was extensive breathy voicing. French showed little
      contextual variation in either direction. Rather surprisingly, the observed
      effects were not directly correlated with, or predictable from, the phonetic
      categories involved (voiced, voiceless unaspirated, and voiceless postaspirated).
      These results yield insights into the control parameters which may be involved in
      regulating voicing oppositions in these languages. Whereas the anticipatory
      effects observed might be consistent with a "timing" model of glottal control,
      the carryover effects cannot be explained in terms of timing alone and suggest
      that differences in tension settings of the laryngeal musculature may also be
      implicated.

PMID- 8277813
TI  - Articulatory representation and speech technology.
AB  - In this paper we demonstrate the feasibility and usefulness of articulation-based
      approaches in two major areas of speech technology: speech recognition and speech
      synthesis. Our articulatory recognition model estimates probabilities of
      categories of manner and place of articulation, which establish the articulatory
      feature vector. The transformation from the articulatory level to the symbolic
      level is performed by hidden Markov models or multi-layer perceptions.
      Evaluations show that the articulatory approach is a good basis for speaker
      independent and speaker-adaptive speech recognition. We are now working on a more
      realistic articulatory model for speech recognition. An algorithm based on an
      analysis by synthesis model maps the acoustic signal to 10 articulatory
      parameters which describe the position of the articulators. EMA (electro-magnetic
      articulograph) measurements recorded at the University of Munich provide good
      initial estimates of tongue coordinates. In order to improve articulatory speech
      synthesis we investigated an accurate physical model for the generation of the
      glottal source with the aid of a numerical simulation. This model takes into
      account nonlinear vortical flow and its interaction with sound-waves. The
      simulation results can be used to improve the articulatory synthesis model
      developed by Ishizaka and Flanagan (1972).

PMID- 8277814
TI  - Purpurogallin: in vivo evidence of a novel and effective cardioprotector.
AB  - We observed that purpurogallin (PPG) which is a flavonoid markedly protects the
      rabbit against myocardial ischemia-reperfusion injury. In rabbits undergoing 1-h
      ligation of the anterior ventricular coronary artery, a bolus infusion of PPG was
      introduced into the post-ischemic heart immediately before 3-h reperfusion.
      Against negligible necrosis in 6 sham-operated controls, and 41.7 (SD 11.3)%
      necrosis in the area at risk for the placebo control group (n = 14 animals), the
      PPG-treated groups (n = 6, 6, 14) had a necrosis of 26.8 (6.4)%, 10.8 (3.5)%, and
      11.7 (5.2)% at doses of 2.5, 5, and 10 mumol/kg, respectively (each with p < 0.01
      vs control value). By comparison, infusion of Trolox (a vitamin E analogue) at 5
      mumol/kg produced a higher necrosis of 17.7 +/- 7.2% (n = 6, p < 0.05 vs value
      obtained from 5 mumol/kg PPG-treated group) in the same model. Note that
      myocardial necrosis was estimated by tetrazolium-based histochemistry and
      confirmed by light and transmission electron microscopies. These data support our
      contention that PPG is an effective cardioprotector, whose mechanism of action
      will be reported separately.

PMID- 8277815
TI  - Effects of phorbol esters on contraction and protein kinase C activation in
      rabbit aorta.
AB  - This study investigates the relationship between the contractile efficacy of
      phorbol esters and their ability to activate protein kinase C in intact rabbit
      aorta. Phorbol dibutyrate (PDB) induced a maximal contraction approximately 3.5
      fold greater than that to phorbol myristate acetate (PMA). The magnitude of
      maximal PDB- and PMA-induced contraction correlated with the magnitude of protein
      kinase C activation, as assessed by the decrease in cytosolic protein kinase C
      activity. KCl (60 mM) did not potentiate the PMA-induced decrease in cytosolic
      protein kinase C activity. These results suggest that the lack of efficacy of PMA
      is due to its inability to activate protein kinase C in the intact rabbit aorta.
      It is speculated that the different contractile efficacies of phorbol esters
      result from selective activation of protein kinase C isoforms, and that the
      amounts of these isoforms varies amongst vascular tissues.

PMID- 8277816
TI  - Stimulation of murine lymphocyte proliferation by a phosphorothioate
      oligonucleotide with antisense activity for herpes simplex virus.
AB  - To investigate further the immunological properties of nucleic acids, the
      mitogenicity of a phosphorothioate oligonucleotide (S-oligo 1082) with antisense
      activity for herpes simplex virus was tested. This compound stimulated
      proliferation and antibody production by murine lymphocytes in in vitro cultures.
      Proliferation was dose-dependent and unaffected by T cell depletion. Furthermore,
      inclusion of a non-mitogenic DNA in the medium did not block stimulation. Since
      1082 does not have homology to a known gene involved in lymphocyte activation,
      these observations suggest that S-oligo antisense compounds may display non
      specific activating effects, at least on murine B cells.

PMID- 8277817
TI  - Identification of binding sites for SR 46349B, a 5-hydroxytryptamine2 receptor
      antagonist, in rodent brain.
AB  - SR 46349B belongs to a new class of compounds (propenone oxime ether derivative)
      that inhibit 5-hydroxytryptamine (HT)2 receptors in vitro and in vivo. (3H) SR
      46349B has been shown to bind with high affinity (Kd = 1.20 nM) to a single class
      of sites in rat prefrontal cortical membranes. The maximum binding capacity (Bmax
      = 0.262 pmol/mg of protein) is similar to that found for other classes of 5-HT2
      receptor antagonists. Although the highest density of specific (3H) SR 46349B
      binding was found in cortex tissue, specific binding was also detectable in other
      brain areas. Among various receptor or channel ligands [including alpha or beta
      adrenergic, dopamine (D1 or D2), histamine (H1 or H2), 5-HT subclasses (5-HT1, 5
      HT3), muscarinic and Na+ and Ca2+ channel blockers] only 5-HT2 receptor effectors
      were able to displace (3H) SR 46349B. In addition, the type of inhibition exerted
      by known 5-HT2 receptor antagonists such as ketanserin and ritanserin was
      investigated by saturation studies. In vivo, (3H) SR 46349B bound predominantly
      in mouse brain regions containing 5-HT2 receptors. This binding was displaced by
      SR 46349B, ketanserin and ritanserin following oral administration. From these
      results we suggest that SR 46349B in its tritiated form is a useful tool to label
      the 5-HT2 receptor in vitro and in vivo.

PMID- 8277818
TI  - Stimulation of phosphoinositide hydrolysis by glyceraldehyde-3-phosphate in
      electroporated HIT-T15 cells.
AB  - HIT-T15 cells labeled with myo-[3H] inositol were permeabilized by
      electroporation and subsequently stimulated with various glycolytic intermediates
      in the presence of 20 mM LiCl in a buffer mimicking cytosolic ionic composition.
      Of the various glycolytic intermediates tested, only D-glyceraldehyde-3-phosphate
      (G3-P) stimulated the formation of labeled inositol phosphates. The half-maximal
      response to G3-P occurred at a concentration of 0.75 mM. Formation of inositol
      phosphates in electroporated cells was also observed in response to GTP. G3-P
      further potentiated the formation of inositol phosphates in response to GTP,
      however, the interaction between G3-P and GTP was additive rather than
      synergistic, indicating that G3-P stimulates phosphoinositide hydrolysis in a
      manner different than the receptor mediated GTP-dependent activation of
      phospholipase C. The potentiation of the GTP response by G3-P did not appear to
      involve inhibition of the GTPase activity of a phosphoinositide-specific G
      protein, since G3-P also potentiated the formation of inositol phosphates in
      response to GTP-gamma-S or NaF in a nearly additive manner.

PMID- 8277819
TI  - Nitric oxide: a signal for ADP-ribosylation of proteins.
AB  - Nitric oxide (NO), a highly reactive gas, is now established as a major messenger
      molecule regulating blood vessel dilation, immune functions and serving as a
      neurotransmitter in brain and peripheral nervous system. NO can also act as a
      tumoricidal and bactericidal molecule. The effect of NO to dilate blood vessels
      is largely explained by stimulation of soluble guanylate cyclase (a heme-iron
      containing protein) leading to formation of cGMP and protein phosphorylation.
      This is considered to be the main physiological signaling mechanism of NO. NO
      also binds to non-heme iron-containing proteins and this has been considered as a
      pathophysiological or cytotoxic action of NO. Furthermore, NO, more correctly
      nitrosonium (NO+) which can be formed by the removal of one electron, reacts with
      protein SH-groups to cause the S-nitrosylation of proteins. We have recently
      established a link between NO and the S-nitrosylation and mono-ADP-ribosylation
      of the enzyme glyceraldehyde 3-monophosphate dehydrogenase, which adds a further
      protein modification mechanism for NO action. This links the formation of the
      second messenger molecule NO to post-translational protein modification and adds
      a new dimension to NO in the communication of intracellular signals.

PMID- 8277820
TI  - Decreased Na,K-ATPase gene expression in cardiomyopathic hamster hearts.
AB  - We studied Na,K-ATPase mRNA expression in cardiomyopathic (Bio 14.6) and normal
      (F1b) Syrian hamster ventricles. In Northern blot analysis, Na,K-ATPase alpha 1,
      alpha 2, alpha 3 and beta 1 isoform mRNAs were detected in 3-week-old Bio 14.6
      and F1b hamster ventricles. We then investigated the expression of alpha 1
      subunit mRNA in Bio 14.6 hamster ventricles at the ages of 3 weeks
      prehypertrophic and 30 weeks hypertrophic, and in age-matched F1b hamster
      ventricles. The alpha 1 subunit mRNA levels in Bio 14.6 hamster ventricles were
      approximately 50% lower than those in F1b hamster ventricles at both 3 and 30
      weeks of age. Na,K-ATPase activity measured in membrane fractions from the
      ventricles of 3-week-old Bio 14.6 hamsters was also approximately 20% lower than
      that of F1b hamsters, suggesting that the differences in the mRNA level were
      associated with the differences in the protein level. We conclude that Na,K
      ATPase mRNA expression and enzyme activity are significantly decreased in the
      hearts of Bio 14.6 hamsters even before the onset of hypertrophy and
      cardiomyopathy, suggesting that the altered expression of Na,K-ATPase gene is an
      early event in the pathogenesis of cardiomyopathy in this animal model.

PMID- 8277821
TI  - Effects of long-term infusion of growth hormone (GH)-releasing factor on
      pulsatile GH secretion in the male rat.
AB  - The effects of long-term infusion of GRF on pulsatile GH secretion were
      investigated in conscious, freely-moving male rats. GH-releasing factor (GRF) was
      intravenously administered for 14 days using an osmotic minipump. Six-hour iv
      infusion of 0.5 microgram/h GRF significantly increased mean GH concentration in
      the conscious rats. In contrast, 14-day iv infusion of 0.5 microgram/h GRF
      significantly inhibited pulsatile GH secretion. The pituitary GH content was
      significantly increased by the 14-day treatment. The GH response to bolus
      injection of 1 microgram GRF under urethane anesthesia was enhanced by the 14-day
      infusion of GRF. Pretreatment with somatostatin (SS) antiserum did not restore
      the inhibited GH secretion in rats treated with 14-day infusion of GRF. These
      results suggest that neither pituitary GH depletion nor high somatostatin tone is
      involved in the GRF-induced GH inhibition.

PMID- 8277822
TI  - Phorbol ester enhances activation of adenylate cyclase in bovine aortic
      endothelial cells.
AB  - Endothelial cells possess beta-adrenoceptors linked to adenylate cyclase which
      may regulate several aspects of endothelial cell function. The potential for this
      second messenger system to be modulated by protein kinase C activity was
      investigated. Bovine aortic endothelial cells (BAECs) were cultured in the
      absence or presence of phorbol 12-myristate 13-acetate (PMA), an activator of
      protein kinase C. Basal and forskolin-, sodium fluoride (NaF)-, and isoproterenol
      stimulated adenylate cyclase activity was measured in homogenates from BAECs.
      beta-adrenoceptor density on membranes from BAECs was measured by 125I
      iodocyanopindolol binding. Sodium dodecylsulfate-polyacrylamide gel
      electrophoresis of immunoprecipitated proteins was used to identify
      phosphorylated proteins. Pretreatment of BAECs with 100 nM PMA for 30 min
      increased basal adenylate cyclase activity above control levels, and also
      increased enzyme activity stimulated by forskolin, NaF, or isoproterenol.
      Pretreatment of BAECs for 60 min with 100 nM staurosporine, an inhibitor of
      protein kinase C, prevented the enhancement of adenylate cyclase activity caused
      by PMA. Treatment of BAECs with PMA did not trigger phosphorylation of the
      inhibitory guanine nucleotide-binding protein, and there was no change in BAEC
      beta-adrenoceptor density following PMA pretreatment. Exposure of BAECs to ATP or
      bradykinin did not mimic the effects of phorbol ester. In conclusion, activation
      of protein kinase C by PMA enhanced adenylate cyclase activity in BAECs. However,
      ATP and bradykinin which activate endothelial cell surface receptors linked to
      phospholipase C did not mimic this effect.

PMID- 8277823
TI  - A study of the physiological mechanisms contributing to neurotensin-induced
      hypothermia.
AB  - Although central administration of neurotensin is known to produce marked
      hypothermia in the rat, there are no studies which have investigated the effects
      of neurotensin on oxygen consumption and heat exchange, the physiological
      mechanisms which are the principal contributors to changes in body temperature.
      We report a significant correlation between dose and the duration and degree of
      post-injection heat loss following central administration of neurotensin. Oxygen
      consumption does not appear to be affected by neurotensin. We suggest that it is
      this dose-dependent, post-injection heat loss which is responsible for
      neurotensin-induced hypothermia. Furthermore, the hypothermia does not appear to
      reflect a change in set point.

PMID- 8277824
TI  - Isolation of brominated long-chain fatty acids from the phospholipids of the
      tropical marine sponge Amphimedon terpenensis.
AB  - Preliminary investigation of the phospholipid fatty acid composition of the
      tropical marine sponge Amphimedon terpenensis by gas chromatography/mass
      spectrometry revealed the presence of some novel brominated fatty acids. Two new
      brominated fatty acids, (5E, 9Z)-6-bromo-5,9-tetracosadienoic acid (2a) and (5E,
      9Z)-6-bromo-5,9-pentacosadienoic acid (3a) were subsequently isolated from a
      chloroform/methanol (3:1, vol/vol) extract of the sponge and characterized as
      their methyl esters 2b and 3b. The known brominated fatty acid (5E, 9Z)-6-bromo
      5,9-hexacosadienoic acid (4a) was also isolated. The new fatty acid methyl esters
      were confirmed as brominated delta 5,9 acid derivatives by chemical ionization
      mass spectrometry. The position of the bromine substituent was determined to be C
      6 by nuclear magnetic resonance techniques while the stereochemistry of the two
      double bonds was deduced by nuclear Overhauser enhancement difference
      spectroscopy. The biosynthetic implications of the co-occurrence of the three
      brominated acids are discussed.

PMID- 8277825
TI  - Synthesis and antitumor activity of 1-beta-D-arabinofuranosylcytosine conjugates
      of optical isomers of ether and thioether lipids.
AB  - Four 1-beta-D-arabinofuranosylcytosine conjugates (ara-C) (1a, b and 2a, b) of sn
      1 and sn-3 isomers of 1-O-octadecyl-2-O-palmitoylglycerol and its 1-S-alkyl
      analogue have been synthesized, and their antitumor activity against L1210
      lymphoid leukemia in mice were compared with those of the previous conjugates
      (3a, b) of racemates in order to determine the significance of chirality of the
      glycerol moieties for activity. Administration (i.p.) of a single dose (300
      mg/kg) of conjugates of sn-1 (1a), sn-3 (2a) and rac (3a) isomers of the ether
      lipid increased lifespan of i.p. implanted L1210 lymphoid leukemic DBA/2J mice by
      169, 175 and 236%, respectively. The sn-1 (1b), sn-3 (2b), and rac (3b) isomers
      of the thioether lipid with a single dose of 300 mg/kg produced an increase in
      lifespan values of 238, 263 and 250%, respectively. The results indicate that
      chirality of the glycerol moieties appears not to be critical for the activity,
      and racemates 3a and 3b are promising prodrugs of ara-C for further clinical
      investigations.

PMID- 8277826
TI  - Sterol synthesis and viability of erg11 (cytochrome P450 lanosterol demethylase)
      mutations in Saccharomyces cerevisiae and Candida albicans.
AB  - The identification of the precise structural features of yeast sterol molecules
      required for the essential "sparking" function has been a controversial area of
      research. Recent cloning and gene disruption studies in Saccharomyces cerevisiae
      have shown that C-24 methylation (ERG6), C-5 desaturation (ERG3) and delta 8
      delta 7 isomerization (ERG2) are not required, while C-14 demethylation (ERG11)
      and C-14 reduction (ERG24) are each required for aerobic viability. Earlier
      observations had indicated that C-14 demethylase deficient strains could be
      restored to aerobic growth by suppressor mutations that caused a deficiency in C
      5 desaturase. These strains were reported to synthesize some ergosterol,
      indicating that they contained leaky mutations in both ERG11 and ERG3, thereby
      making it impossible to determine whether the removal of the C-14 methyl group
      was required for aerobic viability. The availability of the ERG11 and ERG3 genes
      has been used in this study to construct strains that contain null mutants in
      both ERG11 and ERG3. Results show that these double disruption strains are viable
      and that spontaneously arising suppressors of the ERG11 disruption are erg3
      mutants. The erg11 mutants of S. cerevisiae are compared to similar mutants of
      Candida albicans that are viable in the absence of the erg3 lesion.

PMID- 8277827
TI  - Farnesylamine: an inhibitor of farnesylation and growth of ras-transformed cells.
AB  - Farnesylamine, an analogue of farnesol, was shown to inhibit growth of PAP2 cells
      (ras-transformed NIH 3T3 cells) in a dose-dependent manner. This inhibition was
      overcome by adding farnesol to the culture medium, but not by adding
      geranylgeraniol, squalene, cholesterol, dolichol, myristic acid or palmitic acid.
      Farnesylamine inhibited both farnesyl/protein transferase and
      geranylgeranyl/protein transferase in whole cell extracts and also inhibited the
      prenylation of proteins, particularly ras p21, in PAP2 cells. Inhibition of
      prenylation was associated with increased biosynthesis of other products of the
      mevalonate biosynthetic pathway. These observations suggest that inhibition of
      the growth of PAP2 cells by farnesylamine may be due to blocking of ras-mediated
      signal transduction. This offers a means of investigating mechanisms involved in
      ras action and raises the possibility of developing novel strategies for
      anticancer therapy.

PMID- 8277828
TI  - Phospholipid and fatty acid compositions of Rhizobium leguminosarum biovar
      trifolii ANU843 in relation to flavone-activated pSym nod gene expression.
AB  - The phospholipid and associated fatty acid compositions of the bacterial symbiont
      of clover, Rhizobium leguminosarum biovar trifolii wild-type ANU843, was analyzed
      by two-dimensional silica thin-layer chromatography, fast atom bombardment-mass
      spectrometry, flame-ionization detection gas-liquid chromatography and combined
      gas-liquid chromatography/mass spectrometry. The phospholipid composition
      included phosphatidylethanolamine (15%), N-methylphosphatidylethanolamine (47%),
      N,N-dimethylphosphatidylethanolamine (9%), phosphatidylglycerol (19%),
      cardiolipin (5%) and phosphatidylcholine (2%). Fatty acid composition included
      predominantly cis-11-octadecenoic acid, lower levels of cis-9-hexadecenoic acid,
      hexadecanoic acid, 11-methyl-11-octadecenoic acid, octadecanoic acid, 11,12
      methyleneoctadecanoic acid, eicosanoic acid and traces of branched, and di- and
      triunsaturated fatty acids. The influence of expression of the "nodulation" genes
      encoding symbiotic functions on the composition of these membrane lipids was
      examined in wild-type cells grown with or without the flavone inducer, 4',7
      dihydroxyflavone and in mutated cells lacking the entire symbiotic plasmid where
      these genes reside, or containing single transposon insertions in selected
      nodulation genes. No significant changes in phospholipid or associated fatty acid
      compositions were detected by the above methods of analysis.

PMID- 8277829
TI  - Age, sex and source of hamster affect experimental cholesterol cholelithiasis.
AB  - In the present study, we examined the effect of the following factors on a
      hamster model of cholesterol cholelithiasis: (i) the source of the golden Syrian
      hamsters (Sasco, Omaha, NE or Charles River, Wilmington, MA), (ii) the sex of the
      experimental animals and (iii) their age (4 wk vs. 8 wk of age). All hamsters
      were fed a semipurified diet which contained cholesterol (0.3%) and palmitic acid
      (1.2%). No cholesterol gallstones formed in any of the female hamsters regardless
      of age or source. The 4-week-old male hamsters from Sasco had the greatest
      incidence of gallstones (93%). The 8-week-old male hamsters tended to have a
      lower incidence of cholesterol gallstones than the younger ones, regardless of
      the commercial supplier (67 vs. 93% for Sasco and 27 vs. 40% for Charles River).
      Female hamsters had higher liver and serum cholesterol levels than the male
      hamsters; Charles River hamsters had lower serum cholesterol concentrations than
      the Sasco animals. Total biliary lipid concentrations were highest in Sasco male
      hamsters, but biliary cholesterol (mol%) was lower in the males than in the
      females (4.2-4.5% vs. 6.1-7.1%) regardless of age. The cholesterol saturation
      indices were higher in the Sasco females than the corresponding males; these
      values were lower in the Sasco hamsters than the Charles River animals,
      regardless of age or sex. The male Sasco hamsters had a higher total biliary bile
      acid concentration (98.9 mg/mL) than the Sasco females (58.9 mg/mL) and the
      Charles River animals (24.6 mg/mL for males and 38.2 mg/mL for females). The
      percentage of chenodeoxycholic acid in bile was significantly lower, and the
      percentage of cholic acid was higher in all females as compared to
      males.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277830
TI  - An increased incidence of apolipoprotein E2/E2 and E4/E4 in retinitis pigmentosa.
AB  - Previous studies from our laboratory have shown that retinitis pigmentosa (RP), a
      family of hereditary retinal degenerations, is often accompanied by abnormal
      levels of cholesterol or polyunsaturated fatty acids. The requirement of the
      retina for n-3 fatty acids is well known, and a defect in the supply of these
      lipids (e.g., by apolipoproteins) could affect the course of the disease. The
      present study confirms and extends a report on apolipoprotein E (apo E) isoforms
      in German RP patients [Jahn, Oette, Esser, Bergmann, and Leiss, (1987) Ophthalmic
      Res. 19, 285-288] which showed a tenfold increased frequency of the E2/E2
      phenotype compared to the average German population. In our study, apo E
      phenotypes were determined in the probands of 100 Scottish RP families. The
      findings revealed a 4-fold increase in the incidence of E2/E2 and an 8-fold
      increase in E4/E4 compared to a Scottish control population. These increases were
      statistically significant at the P < 0.05 and P < 0.01 levels, respectively. To
      investigate the possibility that some of these apparent E2/E2 or E4/E4 phenotypes
      might actually be new apo E mutations, we examined the behavior of the apo E on
      sodium dodecyl sulfate-polyacrylamide gels (E2 migrates anomalously) and on
      isoelectric focusing gels following cysteamine modification of cysteines. These
      studies showed that two RP patients possibly had new apo E mutations, though
      amino-terminal sequence analysis revealed no changes in the sequence of the first
      19 residues; further sequence analysis is obviously warranted.

PMID- 8277831
TI  - Different resistance of mammalian red blood cells to hemolysis by bile salts.
AB  - To evaluate why hemolysis of red blood cells (RBC) by bile acids varies in
      different mammalian species, we determined the mean corpuscular volume (MCV),
      lipid content and the concentrations of the conjugates of deoxycholate and of
      NaCl inducing 50% hemolysis of RBC from healthy humans, pigs, horses, cows, sheep
      and jaundiced humans. A volume of 0.05 mL of washed RBC at 1% hematocrit, which
      has the same lipid content but different phospholipid composition and number of
      erythrocytes (owing to the variable MCV), was incubated in taurodeoxycholate
      (TDC) solution (0-5 mM) to determine the TDC concentration inducing 50% hemolysis
      (TDC50). The TDC50 was highest in RBC of sheep and decreased within the series
      sheep > pig > cow > horse > healthy human > jaundiced human, which have generally
      increasing MCV. The osmotic resistance followed an inverse order, with jaundiced
      human > healthy human > horse > cow > pig > sheep. Although we found no
      correlation between the TDC50 and phospholipid composition of the erythrocytes
      tested, the extent of bile salt-induced hemolysis seemed to depend on both the
      MCV and the number of erythrocytes in the incubation medium.

PMID- 8277832
TI  - The glyoxalase system in health and disease.

PMID- 8277833
TI  - [Tools for metrological support in measurements of the characteristics of devices
      for radionuclide diagnosis].
AB  - The application of the sets of GSO IGIM-OT, GSO IGIM allows one to introduce the
      unified methods for metrological surveillance in the development, production and
      use medical radiodiagnostic measuring instruments. Using the GSO IGIM, GSO IGIM
      OT, as state reference samples of radionuclide activity in the solid radiometric
      source of ionizing radiation creates the common basis for metrological control of
      the measurement qualities of the characteristics of medical equipment used in
      radionuclide diagnosis.

PMID- 8277834
TI  - [X-ray intensifying screens].
AB  - The paper provides the technical parameters and data of intensifying X-ray
      screens made in Russia. They cover both energy properties (sensitivity, spectral
      characteristics) and the quality of an image (frequency-contrast characteristics,
      granulation). It is shown in what cases this or that class of screens is
      preferable to be used.

PMID- 8277835
TI  - [A high-voltage x-ray spectrometer for x-ray apparatus].
AB  - A high-voltage measuring instrument has been developed to be used in medical X
      ray equipment. It measures without connection up to the current-carrying
      circuits. In the device, the limit of the braking spectrum is used to determine
      the values of X-ray tube-applied voltage, which are calculated to a high
      precision by the programme put into the analyser and printed out on a printer.
      The scale of the device is calibrated by the peak reference points of the
      reference isotopic sources of gamma radiation.

PMID- 8277836
TI  - [The remote electrometry of respiratory musculature function in healthy subjects
      and patients with obstructive lung diseases].

PMID- 8277837
TI  - [Pulse oximetry: the achievements and prospects].

PMID- 8277838
TI  - [A set of equipment for radioimmunochemical diagnosis and radiobiochemical
      research].

PMID- 8277839
TI  - [An analysis of the development and the choice of the future direction of
      cryogenic medical apparatus].
AB  - The paper analyses the available medical cryoequipment and provides strong
      evidence for using the microchoke circuits for the equipment. Moreover, it
      recommends to employ thermoelectric cooling for promising developments of medical
      cryoequipment constructions.

PMID- 8277840
TI  - [Equipment support for the process of controlling cold exposure in biological
      tissue].

PMID- 8277841
TI  - [A rigidity study on the bending of the outer casings of flexible medical
      endoscopes].
AB  - The paper deals with the rigidity of the outer sheaths of flexible medical
      endoscopes for bending on theories and experiments. It also shows that the outer
      plastic sheath connected with a metal braid makes a great contribution to the
      bending rigidity of the sheaths.

PMID- 8277842
TI  - [The direct introduction of the standards of international organizations].

PMID- 8277843
TI  - [An automated system for controlling arterial blood pressure by using
      nitroglycerin infusion].

PMID- 8277844
TI  - [A cardiac intervalometric analyzer (KIM-A)].

PMID- 8277845
TI  - [The Of-VS-01 ophthalmological endoscope].

PMID- 8277846
TI  - [Technical instrumentation for tracheal endoprosthesis].
AB  - By applying the programme-oriented approach, a tracheal X-ray endoscopic
      prosthesis system has been worked out. Medical and technical evidence has been
      provided for the major parameters of the simplest cylindrical endoprosthesis of
      the trachea with the unique location of projections in a two-way spiral line. A
      concise programme has been proposed for calculating the above parameters by using
      the QBASIC language.

PMID- 8277847
TI  - Mitochondrial COII sequences and modern human origins.
AB  - The aim of this study is to measure human mitochondrial sequence variability in
      the relatively slowly evolving mitochondrial gene cytochrome oxidase subunit II
      (COII) and to estimate when the human common ancestral mitochondrial type
      existed. New COII gene sequences were determined for five humans (Homo sapiens),
      including some of the most mitochondrially divergent humans known; for two pygmy
      chimpanzees (Pan paniscus); and for a common chimpanzee (P. troglodytes). COII
      sequences were analyzed with those from another relatively slowly evolving
      mitochondrial region (ND4-5). From class 1 (third codon position) sequence data,
      a relative divergence date for the human mitochondrial ancestor is estimated as
      1/27 th of the human-chimpanzee divergence time. If it is assumed that humans and
      chimpanzees diverged 6 Mya, this places a human mitochondrial ancestor at 222,000
      years, significantly different from 1 Myr (the presumed time of an H. erectus
      emergence from Africa). The mean coalescent time estimated from all 1,580 sites
      of combined mitochondrial data, when a 6-Mya human-chimpanzee divergence is
      assumed, is 298,000 years, with 95% confidence interval of 129,000-536,000 years.
      Neither estimate is compatible with a 1-Myr-old human mitochondrial ancestor. The
      mitochondrial DNA sequence data from COII and ND4-5 regions therefore do not
      support this multiregional hypothesis for the emergence of modern humans.

PMID- 8277848
TI  - The involucrin genes of the mouse and the rat: study of their shared repeats.
AB  - The involucrin genes of the mouse (Mus musculus) and the rat (Rattus norvegicus)
      have been cloned and sequenced. The coding region of each gene contains, at site
      P, a segment of repeats homologous to that of other nonanthropoid mammals. In
      contrast to the repeats of species belonging to different mammalian orders, many
      individual repeats of the mouse and the rat can be matched. Both before and after
      the divergence of the two species, these repeats have been the site of systematic
      alterations in nucleotide sequence. One of the alterations is the correction of
      nucleotides of one repeat by those of another. Corrected nucleotides may be
      closely linked to flanking nucleotides that are uncorrected; the systematic
      correction process therefore appears to be due to gene conversion. There is a
      stretch of 18 reiterated CAGs in the segment of repeats of the Mus gene; most of
      these reiterations were introduced recently, supporting the idea that the gene
      was generated originally from poly CAG. An antiserum to a synthetic peptide
      encoded by the segment of repeats of the Mus gene reveals differentiation
      specific expression of the gene in the epidermis.

PMID- 8277849
TI  - Genetic affinities of inbred mouse strains of uncertain origin.
AB  - Phylogenetic analyses of genetic data arising from 144 gene loci are used to
      describe the interrelationships among 24 widely used inbred strains of mice. An
      unordered-parsimony analysis gives a cladogram that is virtually identical to the
      known genealogy of the mouse strains. A loss-parsimony analysis is used to
      evaluate the hypothesis that the observed patterns of genetic divergence among
      these 24 strains can be explained by the segregation of residual heterozygosity
      arising from a small population of highly heterozygous mice. The loss-parsimony
      cladogram is very similar to both the unordered-parsimony cladogram and the known
      genealogy of the mice. The phylogenetic analyses of these 144 loci are integrated
      with data on the type and origin of the Y chromosome. Inclusion of the Y
      chromosome data provides additional insights into the genetic composition of
      several of the original stocks used to produce the current inbred strains of
      mice. Ten strains of uncertain origin are contained in these analyses, including
      AKR, BUB, CE, I, NZB, P, RF, SJL, ST, and SWR. SJL is hypothesized to have been
      derived from the same Swiss albino stock previously used to produce SWR. The BUB
      strain appears to have had a complex origin and shows closest genetic similarity
      to SWR and ST. AKR and RF are shown to be closely related, while the I strain
      shows greatest genetic similarity to DBA/2 for the 144 loci. However, I and DBA
      possess different types of Y chromosome. The NZB strain shows genetic similarity
      to several stocks of both U.S. and European origins. The power of the genetic
      data used in these analyses reiterates that inbred strains of mice can be a
      valuable paradigm for studies in evolutionary biology.

PMID- 8277850
TI  - Taxonomic congruence versus total evidence, and amniote phylogeny inferred from
      fossils, molecules, and morphology.
AB  - Taxonomic congruence and total evidence are competing paradigms in phylogenetic
      inference. Taxonomic congruence focuses on deriving a consensus from the results
      obtained from separately analyzed data sets, whereas total evidence uses
      character congruence in the search for the best-fitting hypothesis for all of the
      available character evidence. Explicit or implicit use of taxonomic congruence is
      usually employed when an investigator either has both molecular and morphological
      data sets or has different gene-, rRNA-, or protein-sequence data sets available.
      Indeed, a taxonomic congruence rationale is frequently used as the basis for
      exploring classes of data, thus allowing comparison between the phylogenetic
      signal emerging from a particular data set and those of other such classes.
      Problematic aspects of employing the taxonomic congruence approach include the
      potentially misleading and arbitrary choices of both a consensus method and the
      division of characters into subsets. If the goal of an analysis is to provide the
      best estimate of genealogy afforded by the available character evidence, then
      taxonomic congruence is substantially more arbitrary than a total evidence
      approach. The theoretical advantages of phylogenetic estimates based on total
      evidence are argued in the present study and are illustrated with an example of
      amniote relationships. We report conflicting results from total evidence and
      taxonomic congruence approaches, with analyses of previously reported data from
      both fossil and living amniotes and from both morphology and molecules, the
      latter including available 18S rRNA, 28S rRNA, and protein sequences. We conclude
      that a more highly resolved and robust phylogenetic hypothesis of amniotes, the
      traditional one, emerges when a total evidence approach is employed.

PMID- 8277851
TI  - Recovering phylogenetic signal from DNA sequences: relationships within the
      corvine assemblage (class aves) as inferred from complete sequences of the
      mitochondrial DNA cytochrome-b gene.
AB  - Phylogenetic analysis of cytochrome-b sequences and cranial osteological
      characters for nine genera of corvine passerine birds supports the hypothesis
      that the two major groups of birds of paradise, the manucodines and
      paradisaeinines, constitute a monophyletic group and that their postulated sister
      group is the Corvidae (crows, jays, and allies). The data are also consistent
      with the hypothesis that the bowerbirds are not closely related to the birds of
      paradise but instead lie near the base of the corvine assemblage. The corvine
      radiation exemplifies a case of multiple star phylogenies embedded within a major
      clade, with the branching pattern characterized by very short internodal
      divergence times. Such histories are difficult to resolve no matter what type of
      data is employed, because little change accumulates between branching events.
      With respect to sequence data, reconstructed tree topologies are sensitive to the
      choice of outgroup and to the method of analysis (e.g., transversion vs. global
      parsimony). In such cases, assessing the "reliability" of a best-fit or most
      parsimonious tree inferred from any particular data set becomes problematic.
      Statistical tests of tree topologies that depend on random sampling of characters
      will generally be inconclusive in that all cladistic components will tend to be
      poorly supported because relatively few character-state changes will be recorded
      between branching events. It is suggested, on the other hand, that congruence in
      cladistic signal across different data sets may be a potentially more useful
      method for evaluating the reliability of the signal of any one data set.
      Resolution of star phylogenies will probably be possible only if DNA sequence and
      morphological characters are combined in a single analysis.

PMID- 8277852
TI  - Molecular phylogeny and evolutionary rates of alcohol dehydrogenases in
      vertebrates and plants.
AB  - Phylogenetic relationships and evolutionary rates for 36 alcohol dehydrogenases
      (ADHs) from vertebrates and plants are described, with ADHs from fission yeast
      and from baker's yeasts as outgroups. Vertebrate sequences include 15 mammalian,
      2 avian, and 1 amphibian ADH, as well as one sequence deduced from a human
      pseudogene. Plant ADH sequences include 1 from a gymnosperm (loblolly pine) and
      16 from angiosperms, in which 9 sequences are from monocots and 7 are from
      dicots. Phylogenetic analysis shows that ADHs from vertebrates and from plants
      are classified into two distinct groups, and the latter group is further divided
      into angiosperm and gymnosperm ADHs. Among three classes of vertebrate ADHs,
      class I and II ADHs are most closely related and evolved at much faster rates
      than did class III ADHs. The gymnosperm ADH has evolved more slowly than any
      angiosperm ADH. However, ADHs within both of the vertebrate classes I and II and
      class III groups have similar evolutionary rates, as do most of the ADHs within
      the angiosperm group. The rate of amino acid replacement for the vertebrate and
      plant ADHs is approximately 0.3-0.6 x 10(-9)/site/year.

PMID- 8277853
TI  - Reduced natural selection associated with low recombination in Drosophila
      melanogaster.
AB  - Synonymous codons are not used equally in many organisms, and the extent of codon
      bias varies among loci. Earlier studies have suggested that more highly expressed
      loci in Drosophila melanogaster are more biased, consistent with findings from
      several prokaryotes and unicellular eukaryotes that codon bias is partly due to
      natural selection for translational efficiency. We link this model of varying
      selection intensity to the population-genetics prediction that the effectiveness
      of natural selection is decreased under reduced recombination. In analyses of 385
      D. melanogaster loci, we find that codon bias is reduced in regions of low
      recombination (i.e., near centromeres and telomeres and on the fourth
      chromosome). The effect does not appear to be a linear function of recombination
      rate; rather, it seems limited to regions with the very lowest levels of
      recombination. The large majority of the genome apparently experiences
      recombination at a sufficiently high rate for effective natural selection against
      suboptimal codons. These findings support models of the Hill-Robertson effect and
      genetic hitchhiking and are largely consistent with multiple reports of low
      levels of DNA sequence variation in regions of low recombination.

PMID- 8277854
TI  - The lepidopteran mitochondrial control region: structure and evolution.
AB  - For several species of lepidoptera, most of the approximately 350-bp
      mitochondrial control-region sequences were determined. Six of these species are
      in one genus, Jalmenus; are closely related; and are believed to have undergone
      recent rapid speciation. Recent speciation was supported by the observation of
      low interspecific sequence divergence. Thus, no useful phylogeny could be
      constructed for the genus. Despite a surprising conservation of control-region
      length, there was little conservation of primary sequences either among the three
      lepidopteran genera or between lepidoptera and Drosophila. Analysis of secondary
      structure indicated only one possible feature in common--inferred stem loops with
      higher-than-random folding energies--although the positions of the structures in
      different species were unrelated to regions of primary sequence similarity. We
      suggest that the conserved, short length of control regions is related to the
      observed lack of heteroplasmy in lepidopteran mitochondrial genomes. In addition,
      determination of flanking sequences for one Jalmenus species indicated (i) only
      weak support for the available model of insect 12S rRNA structure and (ii) that
      tRNA translocation is a frequent event in the evolution of insect mitochondrial
      genomes.

PMID- 8277855
TI  - Interspecific hybridization in Daphnia: distinction and origin of hybrid
      matrilines.
AB  - Three coexisting Daphnia species belonging to the D. longispina group (D.
      galeata, D. hyalina, and D. cucullata) form species-hybrid complexes by producing
      interspecific hybrids in several lakes in Germany and The Netherlands. To
      evaluate the genetic consequences of interspecific hybridization, I studied the
      patterns of mitochondrial DNA (mtDNA) sequence variation. The directionality of
      interspecific hybridization and divergence of hybrids from parental species was
      tested, using the DNA sequences of a segment of mtDNA. Via the polymerase chain
      reaction, it was possible to investigate single animals and even single resting
      eggs. A species-specific marker was established, using restriction patterns of
      amplified cytochrome b segments. mtDNA genotypes of hybrids revealed
      unidirectional mitochondrial gene flow for two hybrids, which were investigated
      by using multiple clones. No evidence for introgression of mtDNA was found. On
      the basis of a phylogenetic analysis, the species exhibit considerable
      distinctness, whereas differences between clones within species and between
      hybrids and maternal species tend to be very low. These results indicate a recent
      origin of hybrids and suggest that the radiation of the D. longispina group
      occurred > 5 Mya.

PMID- 8277856
TI  - Molecular phylogeny of the symbiotic actinomycetes of the genus Frankia matches
      host-plant infection processes.
AB  - Nucleotide sequences of approximately 213 bp of the nif H-D intergene and the
      beginning of nifD were determined for symbiotic Frankia isolates from the major
      host-infectivity groups. This region of the nif operon is variable enough to
      classify most infective Frankia strains at the species level. Phylogenetic
      inferences from these sequences are in agreement with the 16S rRNA-derived
      phylogeny of the genus and, thus, are in favor of an intrageneric evolution of
      nif genes by orthology. Phylogenetic lineages derived from combined nifH-D
      intergene and partial nifD and 16S rRNA sequences are supported for at least 93%
      of bootstrap replicates and are useful for investigating evolutionary
      relationships of the genus and symbiotic properties of this microorganism. The
      genus Frankia is divided into two major phylogenetic clusters that match with the
      separation of species according to the mechanism of infection of actinorhizal
      plants. One cluster groups species strictly adapted to the mechanism of root hair
      infection (RHI), and the other groups species adapted to the mechanism of direct
      intercellular penetration. In the RHI cluster, the species infective on Casuarina
      plants appears to have emerged from strains infective on Alnus. The concordance
      between the symbiotic properties and the molecular phylogeny of Frankia strains
      indicates a major role for the host plant in the evolution and speciation of the
      genus Frankia.

PMID- 8277857
TI  - Evidence for independent acquisition of group I introns in green algae.
AB  - We report the occurrence of a group I intron, 452 nucleotides in length, in the
      nuclear small-subunit ribosomal gene of the benthic seaweed Urospora
      penicilliformis, a member of the green algal class Ulvophyceae. Group I introns
      have been reported in fungi, myxomycetes, the ciliate genus Tetrahymena, and
      recently in five unicellular chlorophycean algae. The sequence of the conserved
      core of the U. penicilliformis group I intron was aligned with that of 15 other
      introns of this type, and the evolutionary relationships among these introns were
      examined. Comparison of the "intron" tree with phylogenetic hypotheses of the
      intron-harboring organisms shows that nuclear group I introns in green algae have
      arisen several times and are not lineage specific.

PMID- 8277858
TI  - Comparison of the major outer-membrane protein (MOMP) gene of mouse pneumonitis
      (MoPn) and hamster SFPD strains of Chlamydia trachomatis with other Chlamydia
      strains.
AB  - Restriction fragments containing the major outer-membrane protein (MOMP) gene
      from two nonhuman (rodent) strains of Chlamydia trachomatis, the mouse
      pneumonitis (MoPn) strain and the SFPD strain isolated from hamsters with
      transmissible proliferative ileitis, were cloned and sequenced. The MOMP genes of
      both MoPn and SFPD encode an identical 22-amino acid leader peptide and mature
      polypeptides of 365 and 382 amino acids, respectively. Alignment of the MOMP
      genes of the two rodent strains revealed 91% identity. By comparison with other
      known chlamydial MOMP gene sequences, there was 80%-83% identity with human
      biovars strains of C. trachomatis, and there was 69%-70% identity with C.
      psittaci and C. pneumoniae strains. The main differences in these sequences were
      clustered into four variable domains. A minimum-length evolutionary tree was
      constructed on the basis of the MOMP gene variable positions by using PIMA
      package software. The minimum mutation distances indicated that (i) the MOMP
      genes of all chlamydial strains may have evolved from a common ancestor; (ii) all
      the strains of C. trachomatis compose one of the subtrees, and strains of C.
      psittaci and C. pneumoniae compose the other subtree; and (iii) in the C.
      trachomatis subtree, the human and the rodent strains are divided into two
      clusters. The branching pattern of this evolutionary tree is generally consistent
      with current classification based on serological, morphological, and other
      biological characteristics.

PMID- 8277859
TI  - Evolution of duplicate genes in a tetraploid animal, Xenopus laevis.
AB  - To understand the evolution of duplicate genes, we compared rates of nucleotide
      substitution between 17 pairs of nonallelic duplicated genes in the tetraploid
      frog Xenopus laevis with rates between the orthologous loci of human and rodent.
      For all duplicated X. laevis genes, the number of synonymous substitutions per
      site (dS) was greater than the number of nonsynonymous substitutions per site
      (dN), indicating that these genes are subject to purifying selection. There was
      also a significant positive correlation (r = 0.915) between dN for the X. laevis
      genes and dN for the mammalian genes, suggesting that, at the amino acid level,
      the X. laevis genes and the mammalian genes are under similar constraints.
      Results of relative-rate tests showed nearly equal rates of nonsynonymous
      substitution in each copy of the X. laevis genes; apparently there are similar
      constraints on both copies. No correlation was found between dS for the X. laevis
      genes and dS for the mammalian genes. There was a significant positive
      correlation both between members of pairs of duplicated X. laevis genes (r =
      0.951) and between human and rodent orthologues (r = 0.854) with respect to third
      position G+C content but no such relationship between the X. laevis genes and
      either of their mammalian orthologues. The results indicate that both copies of a
      duplicate gene can be subject to purifying selection and thus support the
      hypothesis of selection against all genotypes containing a null allele at either
      of two duplicate loci.

PMID- 8277860
TI  - Molecular mechanisms of colicin evolution.
AB  - This review explores features of the origin and evolution of colicins in
      Escherichia coli. First, the evolutionary relationships of 16 colicin and colicin
      related proteins are inferred from amino acid and DNA sequence comparisons. These
      comparisons are employed to detail the evolutionary mechanisms involved in the
      origin and diversification of colicin clusters. Such mechanisms include movement
      of colicin plasmids between strains of E. coli and subsequent plasmid
      cointegration, transposition- and recombination-mediated transfer of colicin and
      related sequences, and rapid diversification of colicin and immunity proteins
      through the action of positive selection. The wealth of information contained in
      colicin sequence comparisons makes this an ideal system with which to explore
      molecular mechanisms of evolutionary change.

PMID- 8277861
TI  - Maximum-likelihood estimation of phylogeny from DNA sequences when substitution
      rates differ over sites.
AB  - Felsenstein's maximum-likelihood approach for inferring phylogeny from DNA
      sequences assumes that the rate of nucleotide substitution is constant over
      different nucleotide sites. This assumption is sometimes unrealistic, as has been
      revealed by analysis of real sequence data. In the present paper Felsenstein's
      method is extended to the case where substitution rates over sites are described
      by the gamma distribution. A numerical example is presented to show that the
      method fits the data better than do previous models.

PMID- 8277862
TI  - Electronic absorption spectroscopy of copper proteins.
AB  - We have seen from the previous discussion that absorption spectral studies in the
      ligand field region probe the energy splittings of the d orbitals and that this
      relates to the geometry of the metal center. The energies and intensities of
      ligand-to-metal charge transfer transitions sensitively probe bonding
      interactions of the ligand with the metal center. Charge transfer transitions can
      be used both qualitatively to observe ligand binding to a metal center, owing to
      the requirement of orbital overlap for significant charge transfer intensity, and
      quantitatively to define the electron donor ability of that ligand and
      experimentally evaluate the results of electronic structure calculations. Studies
      of the intensities of peaks at the ligand K edge can define the covalent
      interaction of the ligand with the metal valence orbitals, whereas copper K-edge
      spectroscopy is a powerful probe of metal ion oxidation state and the ligand
      field geometry of d10 cuprous sites that are inaccessible through other
      spectroscopic methods. Absorption spectral studies in all regions are strongly
      complemented by CD, variable temperature MCD, and single-crystal polarized
      absorption spectroscopies, which should also be pursued whenever possible to
      obtain detailed electronic structural insight of relevance to catalysis.

PMID- 8277863
TI  - Nanosecond transient absorption spectroscopy.

PMID- 8277864
TI  - Nanosecond time-resolved absorption and polarization dichroism spectroscopies.

PMID- 8277865
TI  - Real-time spectroscopic techniques for probing conformational dynamics of heme
      proteins.

PMID- 8277866
TI  - Variable-temperature magnetic circular dichroism.

PMID- 8277867
TI  - Linear dichroism.

PMID- 8277868
TI  - Infrared spectroscopy.

PMID- 8277869
TI  - Fourier transform infrared spectroscopy.

PMID- 8277870
TI  - Infrared circular dichroism.

PMID- 8277871
TI  - Raman and resonance Raman spectroscopy.

PMID- 8277872
TI  - Electronic absorption spectroscopy of nonheme iron proteins.

PMID- 8277873
TI  - Protein structure from ultraviolet resonance Raman spectroscopy.

PMID- 8277874
TI  - Single-crystal micro-Raman spectroscopy.

PMID- 8277875
TI  - Nanosecond time-resolved resonance Raman spectroscopy.

PMID- 8277876
TI  - Techniques for obtaining resonance Raman spectra of metalloproteins.

PMID- 8277877
TI  - Raman optical activity.

PMID- 8277878
TI  - Surface-enhanced resonance Raman scattering.

PMID- 8277879
TI  - Luminescence spectroscopy.

PMID- 8277880
TI  - Cobalt as probe and label of proteins.

PMID- 8277881
TI  - Circularly polarized luminescence.

PMID- 8277882
TI  - Low-temperature stopped-flow rapid-scanning spectroscopy: performance tests and
      use of aqueous salt cryosolvents.
AB  - An ultimate goal of enzymology is to determine the structure of intermediates in
      catalysis in solution. Metalloenzymes provide a unique opportunity in this regard
      because the metal atom is critical to catalysis. In the case of zinc enzymes,
      replacement of the zinc by the chromophoric cobalt atom can result in the
      identification of intermediates in catalysis. This is most easily accomplished by
      examining the enzyme-catalyzed reaction under rapid-mixing and rapid-scanning
      subzero conditions. Aqueous salt solutions are particularly useful as
      cryosolvents whenever hydrophobic forces are important for substrate binding.
      Rapid-freeze or chemical quenching of these metallointermediates can allow
      further structural characterization by such approaches as EPR spectroscopy and X
      ray absorption fine structure. Such a combination of approaches can bridge the
      information gained by examining only the structure of the enzyme in the
      crystalline state by X-ray diffraction and that obtained by examining only steady
      state enzymatic activities.

PMID- 8277883
TI  - Transition-metal complexes as spectroscopic probes for selective covalent
      labeling and cross-linking of proteins.

PMID- 8277884
TI  - Ruthenium complexes as luminescent reporters of DNA.

PMID- 8277885
TI  - Detecting metal-metal interactions and measuring distances between metal centers
      in metalloproteins.

PMID- 8277886
TI  - Biochemical and spectroscopic probes of mercury(II) coordination environments in
      proteins.

PMID- 8277887
TI  - Low-temperature optical spectroscopy: metalloprotein structure and dynamics.

PMID- 8277888
TI  - Autonomy in midwifery and maternity care.

PMID- 8277889
TI  - "Free speech": power games in midwifery.

PMID- 8277890
TI  - Do women really have a choice?

PMID- 8277891
TI  - Be prepared!

PMID- 8277893
TI  - Whose move in midwifery education?

PMID- 8277892
TI  - Postnatal depression.

PMID- 8277894
TI  - 13th Dame Rosalind Paget Memorial Lecture. The power of influence.

PMID- 8277895
TI  - End to placental collection.

PMID- 8277896
TI  - International Confederation of Midwives. "Midwives, hear the heartbeat of the
      future".

PMID- 8277897
TI  - Care study: pregnancy and Ehlers-Danlos syndrome type IV.

PMID- 8277899
TI  - "Farewell to the midwives' midwife"--a profile of Margaret Brain, OBE. Interview
      by Suzanne Tyler.

PMID- 8277898
TI  - The Royal College of Midwives education department.

PMID- 8277900
TI  - Thumbs down to PREP.

PMID- 8277901
TI  - Men's attitudes to breast-feeding.

PMID- 8277902
TI  - Providing continuity: the experience of midwives.

PMID- 8277903
TI  - Freedom to choose--a global perspective.

PMID- 8277904
TI  - Just the job. Interview by Elizabeth Duff.

PMID- 8277905
TI  - Homelessness: a midwifery perspective.

PMID- 8277906
TI  - AIDS--time to act.

PMID- 8277907
TI  - Whose breast is best? Trends in infant feeding in early modern England.

PMID- 8277908
TI  - "Free speech": "duo" midwives.

PMID- 8277909
TI  - [Role of putrescine in the antiporter mechanism of potassium transport in
      Escherichia coli and its role in the regulation of intracellular pH].
AB  - The interrelation between the Escherichia coli transport processes of K+ and
      putrescine+2 was investigated under the inhibition and limitation of the main
      energy consuming potassium transport systems (Trk, Kdp). It was shown that the
      potassium addition to the potassium deprived putrescine loaded cells triggers the
      putrescine exit at the exchange on the potassium. The stoichiometry of putrescine
      +2/2K+ translocation provide the electroneutrality of this process. The
      putrescine gradient turnover changes the potassium transport direction on the
      opposite one. The submitted experimental data are the evidence of putrescine
      +2/2K+ antiporter existence. The role of this antiporter in the E. coli pH
      homeostasis is discussed.

PMID- 8277910
TI  - [Methane fermentation of cattle manure at low temperature].
AB  - The acclimated microbial association fermenting cattle manure at 6 degrees C with
      methane production was obtained by a long-time (2.5 years) autoselection. It is
      shown that the basic barrier to carry out this process at low temperature is long
      time period of adaptation of microbial community. It is removed by addition of
      the psychrophilic barm obtained. After cultivating of this psychrophilic
      methanogenic association under mesophilic (35 degrees) and thermophilic (55
      degrees) conditions its activity decreased to 2 and 10 times, respectively. Based
      on the kinetic estimations it was proposed, that the essential changes of
      properties of the anaerobic microflora investigated was occurred during the
      acclimation to low temperature. The psychrotrophic microorganisms played the main
      role in the process of organic matter degradation at low temperature in the
      studied system. The pure cultures of saccharolitic and acetogenic psychrotrophic
      bacteria those are capable to grow in the wide range of temperature, from 0
      degrees to 35 degrees C were isolated. Methanosarcina and methanothrix ix were
      detected in the enrichment cultures growing with acetate at 6 degrees C.

PMID- 8277911
TI  - [Effect of nitrites-polluted environment on the viability of individual species
      of bacteria of the genus Bacillus].

PMID- 8277912
TI  - Piperacillin/tazobactam.

PMID- 8277913
TI  - Topical minoxidil for baldness: a reappraisal.

PMID- 8277914
TI  - The puzzle of cocaine's effects following maternal use during pregnancy: are
      there reconcilable differences?
AB  - This is a selective review of the clinical and epidemiological literature. It
      attempts to reconcile disparate and contradictory findings dealing with the
      morphologic, growth, and neurobehavioral effects reported to occur in neonates
      and young children exposed prenatally to cocaine. A history of cocaine use in the
      United States is briefly presented followed by impressionistic observations of
      some of the events that transpired during the cocaine epidemic of the 1980s.
      Based on the collective research findings, it is tentatively suggested that the
      teratogenic effects of prenatal cocaine may be produced only in those infants
      exposed to the highest doses reported in the literature. It remains unknown,
      however, whether or not these effects may be dependent on the concurrent abuse of
      alcohol and/or cigarettes. As to growth and neurobehavioral outcomes, effects
      attributable primarily to cocaine alone and not other substances of abuse appear
      to be only marginal and transitory. The data to support these conclusions are
      particularly tenuous and are thus offered only as working hypotheses. Because of
      the intractable methodological and interpretive problems inherent in human
      developmental research on substance abuse, any attempt to draw definitive
      conclusion is admittedly premature. Because these methodological problems also
      complicate the efforts of ongoing studies, answers to these persistent questions
      may not be readily forthcoming.

PMID- 8277915
TI  - Missing pieces of the puzzle.

PMID- 8277916
TI  - Does cocaine cause birth defects?

PMID- 8277917
TI  - Saying "goodbye" to the "crack baby".

PMID- 8277918
TI  - Cocaine use and crack babies: science, the media, and miscommunication.

PMID- 8277919
TI  - The puzzle of cocaine's effects following maternal use during pregnancy: still
      unsolved.

PMID- 8277920
TI  - Puzzle of cocaine's effects following maternal use during pregnancy: are there
      reconcilable differences?

PMID- 8277921
TI  - Children exposed to cocaine prenatally: pieces of the puzzle.

PMID- 8277922
TI  - Cocaine and the human fetus: the concept of teratophilia.

PMID- 8277923
TI  - Cocaine and the fetus: mythology of severe risk.

PMID- 8277924
TI  - Missing pieces of the puzzle complicate conclusions about cocaine's
      neurobehavioral toxicity in clinical populations: importance of animal models.

PMID- 8277925
TI  - Neurotoxicologic examination of rats exposed to 1,1,1-trichloroethane vapor for
      13 weeks.
AB  - Large evoked potential and EEG changes occurred in a pilot study in Fisher 344
      rats during exposure to 2000 ppm of 1,1,1-trichloroethane (1,1,1-T; a cleaning
      solvent with anesthetic properties). In the main study, rats were evaluated for
      persistent nervous system effects the week following exposure to 0, 200, 630, or
      2000 ppm 1,1,1-T for 6 h/day, 5 days/week, for 13 weeks. Rats were clinically
      examined regularly and were given a functional observational battery monthly
      (FOB, including forelimb and hindlimb grip performance testing). After 13 weeks
      of exposure, the rats were evaluated by FOB and by visual, auditory,
      somatosensory, and caudal nerve-evoked potentials. After functional testing, a
      subgroup of rats had histopathologic examination of brain, spinal cord,
      peripheral nerves, and limb muscles. There were no post-exposure treatment
      related findings in any parameter (FOB observations plus 39 dependent variables)
      except for a slightly smaller forelimb grip performance in the 2000-ppm exposure
      group. There was no recognized toxicologic significance for the difference in
      forelimb grip performance; a lack of findings in any other clinical, evoked
      potential or morphologic parameter did not support a diagnosis of neurotoxicity.

PMID- 8277926
TI  - Effects of toluene, styrene, trichloroethylene, and trichloroethane on the
      vestibulo-and opto-oculo motor system in rats.
AB  - The acute effects of inhalation of four solvents on the central vestibular system
      of rats were analyzed by recording eye movements upon different stimuli. The dose
      response relationship was investigated. Optokinetic stimulation was obtained by
      placing the animals in front of a surrounding visual pattern, moving at different
      velocities. The slow-phase eye velocity (SPV) of nystagmus was calculated and
      divided by the stimulus velocity, giving the gain. All the solvents caused a
      decrease of the gain. Vestibular stimulation was performed on a turntable by an
      angular acceleration/deceleration in darkness. The SPV and the duration of the
      post-stimulatory nystagmus were calculated. The shape of the SPV dose-response
      curves differed among the four solvents. Toluene, styrene, and trichloroethylene
      prolonged the duration of nystagmus while trichloroethane did not. A conflicting
      vestibular and optokinetic stimulation was performed by an angular
      acceleration/deceleration with a surrounding visual pattern moving with the
      turntable. All solvents decreased the ability to cancel nystagmus, elicited by
      vestibular stimulation in conflict with a visual input. Quick movements of the
      eyes, saccades, were elicited by tactile stimulation. Toluene, styrene, and
      trichloroethylene changed the generation of the saccades while trichloroethane
      did not. Most of the findings indicate a common site of action in the central
      vestibular system, viz, the cerebellar-vestibular circuit. However, within this
      domain, there are evident differences in the effects among the solvents. This
      findings, together with previous results obtained in other experimental models of
      the central nervous system (CNS), suggest that different solvents should be
      considered as individual compounds.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277927
TI  - Intravenous gestational cocaine in rats: effects on offspring development and
      weanling behavior.
AB  - Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of
      saline (SAL), via the tail vein, on gestation days 8-20. A third group was
      untreated (UT). Maternal weight gain was not affected by dam treatment despite
      slight differences in food intake. Litter characteristics (e.g., litter size, pup
      weight) did not differ among groups. Indices of fetal mortality were not affected
      by the treatments. Developmental tests, initiated on postnatal day (PND) 2,
      indicated slight delays in the negative geotaxic response and eye opening in
      cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21.
      Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no
      treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or
      saline was injected prior to the tail flick test. Pups from CN dams exhibited a
      significant decrease in spontaneous exploratory behavior compared to both
      controls, and a time-dependent increase in rearing compared to pups from UT dams.
      The acute cocaine injection prior to placement in the open field did not alter
      locomotion or rearing among dam treatment groups. However, the acute cocaine
      injection did increase stereotypy ratings for female pups from CN dams compared
      to similarly treated males, and females from SAL and UT dams. No differences were
      observed among groups in the tail-flick test. These data suggest that the IV
      route of administration provides a viable method of cocaine delivery in pregnant
      rats, and provides further evidence of the developmental and behavioral
      teratogenicity of prenatal cocaine exposure.

PMID- 8277928
TI  - Structure-toxicity relationship of monoketones: in vitro effects on beta
      adrenergic receptor binding and Na(+)-K(+)-ATPase activity in mouse synaptosomes.
AB  - The structure-toxicity relationship of monoketones, a class of organic solvents
      widely used in industry, was investigated with respect to their in vitro effects
      on synaptosomal membrane proteins. The toxic parameters used were Na(+)-K(+)
      adenosine triphosphatase (Na(+)-K(+)-ATPase), a well-known marker enzyme often
      used as a membrane toxicity model, and 3H-dihydroalprenolol (3H-DHA)-labeled beta
      adrenergic receptor binding that has been shown to be vulnerable to solvent
      induced changes in membrane fluidity. In vitro treatments with 12 kinds of
      monoketones (carbon chain length from 3-10) dose-dependently inhibited both 3H
      DHA binding to mouse synaptosomes and Na(+)-K(+)-ATPase activity. The potency of
      inhibition (IC50) for both the two parameters was linearly related to n
      octanol/water partition coefficient and synaptosome/buffer partition coefficient
      of the test compounds. Additions of monoketones did not significantly alter the
      number of 3H-DHA binding sites but markedly decreased their affinity. In each
      monoketone, the IC50 values for 3H-DHA binding and Na(+)-K(+)-ATPase activity
      were generally within the same range. The anisotropy of fluorescence probe 1,6
      diphenyl-1,3,5-hexatriene-labeled synaptosomal membranes was dose-dependently
      decreased by the monoketones, implying increased membrane fluidity. These results
      indicate that increasing lipophilicity of monoketones results in increased
      solvent penetration of synaptic membrane preparations, leading to conformational
      changes in membrane structure and increased ability to inhibit both neuroreceptor
      binding and enzyme activity. The present data confirm the importance of the lipid
      micro-environment of membranes in maintaining the normal functions of membrane
      bound proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277929
TI  - Does anyone know where we are?

PMID- 8277930
TI  - You mean all of this is over five bucks?

PMID- 8277932
TI  - Health reform: license to kill.

PMID- 8277931
TI  - Dermatology quiz #8. Mycosis fungoides.

PMID- 8277933
TI  - Exposure to environmental tobacco smoke among Missouri children.
AB  - Childhood exposure to environmental tobacco smoke (ETS) increases the risk of
      lower respiratory infections (e.g., bronchitis and pneumonia), exacerbates
      childhood asthma, and increases the prevalence of fluid in the middle ear. Using
      self-reported telephone survey data, we examined the attitudes and practices of
      Missouri residents related to ETS exposure of children. Ninety-five percent of
      all respondents believed that ETS exposure is harmful to children and the
      percentage was similar for households with children (96%) and without children
      (94%). ETS was present in 42% of households and the percentage was similar for
      households with children (41%) and without children (44%). Childhood exposure to
      ETS remains a problem in Missouri, despite widespread awareness of the hazards.
      More active intervention is needed to reduce ETS exposure in the home.

PMID- 8277934
TI  - Computerized medical records--new opportunities.
AB  - The new generation of computer hardware and software is providing many new
      opportunities for physicians to use computerized medical records in their
      practices. A substantial number of new commercial systems have been introduced
      within the past few years, and many more will likely become available soon. In
      addition, there are opportunities for physicians to create their own customized
      systems using new software tools now available.

PMID- 8277936
TI  - Testosterone pellet implant therapy for lichen sclerosus.
AB  - Lichen sclerosus is a benign chronic skin disease predominantly affecting the
      vulva in post-menopausal women. Various methods of therapy have been recommended
      for this stubborn and uncomfortable condition. The article describes a new method
      of therapy for patients suffering from this disorder, utilizing subcutaneously
      implanted testosterone pellets to obtain extended remission of symptoms.

PMID- 8277935
TI  - Prevention--the forgotten reform.
AB  - Almost everyone agrees that America needs a more efficient and equitable health
      care system. But reforms in these areas alone are not sufficient, for they do
      little to address the great nation-wide burden of illness that demands expensive
      care in the first place. Reinforced prevention is the forgotten component in
      health care reform. There is false security in relying upon individual behavior
      change alone to reduce the burden of illness. Instead, we need a broader vision
      of public health strategy in which key health-oriented policies become law, and
      are more effective. It is time to call on our President and Congress to uphold
      their responsibility to protect health through such policies, and thus stem some
      of the root causes of our crisis.

PMID- 8277937
TI  - Drug-resistant Streptococcus pneumoniae--Kentucky and Tennessee, 1993.
AB  - Streptococcus pneumoniae is the most common bacterial cause of pneumonia
      worldwide in children and adults and a leading cause of sepsis and meningitis. In
      addition, it is the etiology of 30%-50% of episodes of acute otitis media, the
      most frequent reason for pediatric office visits in the United States
      (approximately 24.5 million per year). Because sensitive and rapid diagnostic
      tests are not available, most pneumococcal infections are treated empirically;
      until recently, penicillin (PCN) and related drugs have been the treatment of
      choice. However, because of the emergence of infections with drug-resistant S.
      pneumoniae (DRSP), decisions regarding the management of infections caused by
      this pathogen have become increasingly complicated. This report summarizes
      results of recent investigations by CDC and state public health officials of DRSP
      in communities in Kentucky and Tennessee.

PMID- 8277938
TI  - Characteristics of women receiving family planning services at Title X clinics-
      United States, 1991.
AB  - In 1970, enactment of federal legislation created a national family planning
      program funded under Title X of the Public Health Services Act. Since the
      enactment of this legislation, clinics funded entirely or partially by Title X
      have been the primary source of subsidized family planning services in the United
      States. Although information characterizing women who receive family planning
      services at Title X clinics can assist in program planning and operations, such
      information has not been compiled at the national level since 1981. In 1992,
      state family planning administrators and CDC, with cooperation from Title X
      grantees, initiated the Family Planning Services Surveillance (FPSS) project to
      characterize women receiving family planning services from Title X clinics in
      1991. This report presents the findings of FPSS.

PMID- 8277939
TI  - Isolation and characterization of a maize gene encoding chalcone flavonone
      isomerase.
AB  - We report here the first cloning of a chalcone flavonone isomerase gene (CHI)
      from maize. Northern blot experiments indicate that the maize CHI gene (ZmCHI1)
      is regulated in the pericarp by the P gene, a myb homologue. The ZmCHI1 gene
      encodes a 24.3 kDa product 55% and 58% identical to CHI-A and CHI-B from Petunia,
      respectively. This maize CHI1 gene has four exons and an intron-exon structure
      identical to the CHI-B gene of Petunia hybrida. RFLP mapping data indicate that
      some inbred lines contain two additional CHI-homologous sequences, suggesting an
      organization more complex than that found in Petunia or bean. The possibility
      that the additional CHI-homologous sequences are responsible for the lack of CHI
      mutants in maize will be discussed.

PMID- 8277940
TI  - In vivo analysis of chromatin following nystatin-mediated import of active
      enzymes into Saccharomyces cerevisiae.
AB  - In vivo DNA-protein interactions are usually studied at the molecular level using
      DNA-degrading agents of low molecular weight. In order to be useful,
      macromolecular probes of chromatin structure, such as enzymes must first cross
      the cell membrane. In this paper we describe the introduction and evaluation of
      macromolecules with enzymatic activity into yeast spheroplasts treated with the
      polyene antibiotic nystatin. We report the low resolution analysis of chromatin
      structure in the promoter region of the Saccharomyces cerevisiae gene encoding
      DNA topoisomerase I by this technique using micrococcal nuclease and restriction
      enzymes.

PMID- 8277941
TI  - Comparative amino acid sequence analysis of Thermotoga maritima beta-glucosidase
      (BglA) deduced from the nucleotide sequence of the gene indicates distant
      relationship between beta-glucosidases of the BGA family and other families of
      beta-1,4-glycosyl hydrolases.
AB  - The primary structure of the bglA gene region encoding a beta-glucosidase of
      Thermotoga maritima strain MSB8 was determined. The bglA gene has the potential
      to code for a polypeptide of 446 amino acids with a predicted molecular mass of
      51,545 Da. The T. maritima beta-glucosidase (BglA) was overexpressed in E. coli
      at a level comprising approximately 15-20% of soluble cellular protein. Based on
      its amino acid sequence, as deduced from the nucleotide sequence of the gene,
      BglA can be classified as a broad-specificity beta-glucosidase and as a member of
      the beta-glucosidase family BGA, in agreement with the results of enzymatic
      characterization of the recombinant protein. Comparative sequence analysis
      revealed distant amino acid sequence similarities between BGA family beta
      glucosidases, a beta-xylosidase, beta-1,4-glycanases of the enzyme family F
      (mostly xylanases), and other families of beta-1,4-glycosyl hydrolases. This
      result indicates that BGA beta-glucosidases may comprise one enzyme family within
      a large 'enzyme order' of retaining beta-glycosyl hydrolases, and that the
      members of these enzyme groups may be inter-related at the level of active site
      architecture and perhaps even on the level of overall three-dimensional fold.

PMID- 8277942
TI  - Molecular cloning, sequence and regulation of expression of the recA gene of the
      phototrophic bacterium Rhodobacter sphaeroides.
AB  - The recA gene of Rhodobacter sphaeroides 2.4.1 has been isolated by
      complementation of a UV-sensitive RecA- mutant of Pseudomonas aeruginosa. Its
      complete nucleotide sequence consists of 1032 bp, encoding a polypeptide of 343
      amino acids. The deduced amino acid sequence displayed highest identity to the
      RecA proteins from Rhizobium meliloti, Rhizobium phaseoli, and Agrobacterium
      tumefaciens. An Escherichia coli-like SOS consensus region, which functions as a
      binding site for the LexA repressor molecule was not present in the 215 bp
      upstream region of the R. sphaeroides recA gene. Nevertheless, by using a recA
      lacZ fusion, we have shown that expression of the recA gene of R. sphaeroides is
      inducible by DNA damage. A recA-defective strain of R. sphaeroides was obtained
      by replacement of the active recA gene by a gene copy inactivated in vitro. The
      resulting recA mutant exhibited increased sensitivity to UV irradiation, and was
      impaired in its ability to perform homologous recombination as well as to trigger
      DNA damage-mediated expression. This is the first recA gene from a Gram-negative
      bacterium that lacks an E. coli-like SOS box but whose expression has been shown
      to be DNA damage-inducible and auto-regulated.

PMID- 8277943
TI  - Cloning and characterisation of the cytochrome c gene of Aspergillus nidulans.
AB  - The cytochrome c gene (cycA) of the filamentous fungus Aspergillus nidulans has
      been isolated and sequenced. The gene is present in a single copy per haploid
      genome and encodes a polypeptide of 112 amino acid residues. The nucleotide
      sequence of the A. nidulans cycA gene shows 87% identity to the DNA sequence of
      the Neurospora crassa cytochrome c gene, and approximately 72% identity to the
      sequence of the Saccharomyces cerevisiae iso-1-cytochrome c gene (CYC1). The S.
      cerevisiae CYC1 gene was used as a heterologous probe to isolate the homologous
      gene in A. nidulans. The A. nidulans cytochrome c sequence contains two small
      introns. One of these is highly conserved in terms of position, but the other has
      not been reported in any of the cytochrome c genes so far sequenced. Expression
      of the cycA gene is not affected by glucose repression, but has been shown to be
      induced approximately tenfold in the presence of oxygen and three- to fourfold
      under heat-shock conditions.

PMID- 8277944
TI  - A pleiotropic acid phosphatase-deficient mutant of Escherichia coli shows
      premature termination in the dsbA gene. Use of dsbA::phoA fusions to localize a
      structurally important domain in DsbA.
AB  - A one-step mutant of Escherichia coli K-12 lacking both glucose-1-phosphatase
      (Agp) and pH 2.5 acid phosphatase (AppA) activities in the periplasmic space was
      isolated. The mutation which mapped close to chlB, at 87 min on the E. coli
      linkage map, also caused the loss of alkaline phosphatase (PhoA) activity, even
      when this activity was expressed from TnphoA fusions to genes encoding
      periplasmic or membrane proteins. A DNA fragment that complements the mutation
      was cloned and shown to carry the dsbA gene, which encodes a periplasmic
      disulphide bond-forming factor. The mutant had an ochre triplet in dsbA,
      truncating the protein at amino acid 70. Introduction of TnphoA fusions into a
      plasmid-borne dsbA gene resulted in DsbA-PhoA hybrid proteins that were all
      exported to the periplasmic space in both dsbA+ and dsbA strains. They belong to
      three different classes, depending on the length of the DsbA fragment fused to
      PhoA. When PhoA was fused to an amino-terminal DsbA heptapeptide, the protein was
      only seen in the periplasm of a dsbA+ strain, as in the case of wild-type PhoA.
      Hybrid proteins missing up to 29 amino acids at the carboxy-terminus of DsbA were
      stable and retained both the DsbA and PhoA activities. Those with shorter DsbA
      fragments that still carried the -Cys-Pro-His-Cys- motif were rapidly degraded
      (no DsbA activity). The presence is discussed of a structural domain lying around
      amino acid 170 of DsbA and which is probably essential for its folding into a
      proteolytic-resistant and enzymatically active form.

PMID- 8277945
TI  - Relationship between zinc content and DNA-binding activity of the DNA-binding
      motif of the transcription factor ALCR in Aspergillus nidulans.
AB  - The transcription factor ALCR of the ethanol utilisation pathway in Aspergillus
      nidulans contains a zinc binuclear motif (CysX2CysX6CysX16CysX2CysX6Cys), within
      the DNA-binding domain located in the N-terminal region of the ALCR protein.
      Specific targets have been localised in the promoter of the alcR gene, involved
      in the autoregulation process, and in the promoter of the structural gene alcA
      (encoding alcohol dehydrogenase I), which is also under the control of ALCR. The
      DNA-binding domain has been expressed in-Escherichia coli as a GST-ALCR (7-58*)
      fusion protein and also obtained as an ALCR (7-58*) peptide. Both the ALCR fusion
      protein and the ALCR peptide are able to bind 65Zn(II) in vitro, if reduction of
      cysteines occurs prior to the addition of zinc. Competition experiments showed
      that Cd(II), Co(II) and Cu(II) are efficient competitors for the zinc binding
      sites. The ALCR DNA-binding domain was shown to contain 2 mol of tightly bound
      Zn(II) per mole of fusion protein. Removal of the intrinsic Zn(II) requires
      treatment with Chelex. This treatment abolishes the ability of the protein to
      bind to the targets of ALCR located in the alcA and alcR promoters. The apo-ALCR
      DNA-binding motif could be reconstituted with Zn(II) or Cd(II), restoring
      specific DNA binding to both types of targets. Thus a direct relationship was
      shown to exist between the zinc content of ALCR and its DNA-binding activity.

PMID- 8277946
TI  - Analysis of the regulation of penicillin biosynthesis in Aspergillus nidulans by
      targeted disruption of the acvA gene.
AB  - To analyse the regulation of the biosynthesis of the secondary metabolite
      penicillin in Aspergillus nidulans, a strain with an inactivated acvA gene
      produced by targeted disruption was used. acvA encodes delta-(L-alpha
      aminoadipyl)-L-cysteinyl-D-valine synthetase (ACVS), which catalyses the first
      step in the penicillin biosynthetic pathway. To study the effect of the
      inactivated acvA gene on the expression of acvA and the second gene, ipnA, which
      encodes isopenicillin N synthase (IPNS), A. nidulans strain XEPD, with the acvA
      disruption, was crossed with strain AXB4A carrying acvA-uidA and ipnA-lacZ fusion
      genes. Ascospores with the predicted non-penicillin producing phenotype and a
      hybridization pattern indicating the presence of the disrupted acvA gene, and the
      fusion genes integrated in single copy at the chromosomal argB locus were
      identified. Both fusion genes were expressed at the same level as in the non
      disrupted strain. Western blot analysis (immunoblotting) revealed that similar
      amounts of IPNS enzyme were present in both strains from 24 to 68 h of a
      fermentation run. In the acvA disrupted strain, IPNS and acyl-CoA: 6
      aminopenicillanic acid acyltransferase (ACT) specific activities were detected,
      excluding a sequential induction mechanism of regulation of the penicillin
      biosynthesis gene ipnA and the third gene aat.

PMID- 8277947
TI  - RNA editing of a conserved reading frame in plant mitochondria increases its
      similarity to two overlapping reading frames in Escherichia coli.
AB  - An open reading frame (orfx) in mitochondria of the higher plants Oenothera
      berteriana and Arabidopsis thaliana is homologous to orf244 in the mitochondrial
      genome of Marchantia polymorpha. Homologous sequences are also present in carrot,
      potato and sugar beet. Profile analysis revealed similarity to two overlapping
      reading frames in the Escherichia coli genome. Potential translation initiation
      at conserved ATA (isoleucine) and TTG (leucine) codons is discussed. Transcripts
      of the open reading frame are altered by RNA editing in Arabidopsis and Oenothera
      downstream of these codons, suggesting this to be the functionally important
      region.

PMID- 8277948
TI  - Nucleotide sequence analysis and potential environmental distribution of a ferric
      pseudobactin receptor gene of Pseudomonas sp. strain M114.
AB  - The nucleotide sequence of the Pseudomonas sp. strain M114 pbuA gene, encoding
      the outer membrane receptor for ferric pseudobactin M114, has been determined.
      The region sequenced spans 2788 bases of plasmid pCUP3, within which the receptor
      gene had previously been localised. A single open reading frame, potentially
      encoding 826 amino acids and including a leader peptide of 44 amino acids, is
      evident and is followed by an inverted repeat segment, which may act as a
      transcriptional terminator. A 20 bp region of DNA, having significant homology
      with the E. coli Fur-binding consensus sequence, is located upstream of the open
      reading frame. PbuA displays characteristics in common with other outer membrane
      proteins and displays strong homology with the TonB boxes of both E. coli and
      Pseudomonas receptors. More extensive homologies were found with the PupA
      receptor of P. putida WCS358 and the FhuE and BtuB receptors of E. coli. It is
      suggested that areas exhibiting the least homology between these receptors may
      represent ferric siderophore-specific recognition sites of the PbuA protein. The
      deduced amino acid sequence of pbuA was compared with that of pupX, encoding the
      outer membrane receptor for ferric pseudobactin B10, of Pseudomonas sp. strain B
      10. A direct alignment of the two proteins gave an identity score of 92.5%. The
      distribution of PbuA-like receptors among Pseudomonas isolates was investigated
      by DNA-DNA hybridisation analysis. The results suggest that a PbuA-like receptor
      may be widely distributed among Pseudomonas rhizosphere isolates.

PMID- 8277949
TI  - Role of two operators in regulating the plasmid-borne raf operon of Escherichia
      coli.
AB  - The plasmid-borne raf operon encodes functions required for the inducible uptake
      and utilization of raffinose in Escherichia coli K12. The expression of three
      structural genes for alpha-galactosidase (rafA), Raf permease (rafB) and sucrose
      hydrolase (rafD) is negatively controlled by the binding of RafR repressor (rafR)
      to two operator sites, O1 and O2, that flank the -35 sequence of the raf
      promoter, PA. In vitro, O1 and O2 are occupied on increasing the concentration of
      RafR, without detectable preference for one site or the other or any indication
      of cooperative binding. Nucleotide substitutions at positions 3, 4 or 5 in an
      operator half-site prevented repressor binding, supporting a model that
      postulates specific interactions of these base pairs with the recognition helix
      of RafR. To study the role of each operator site, we have compared by gel shift
      analysis the binding of purified RafR repressor to DNA fragments containing the
      original O1O2 configuration or mutant O1 or O2. When either one of the two
      operators was inactivated by site-directed mutagenesis, both O1 and O2 exhibited
      the same affinity for repressor and the same sensitivity to arrest of repressor
      binding by the natural inducer, melibiose. However, in the native O1O2
      configuration, simultaneous binding of RafR to both operators was sterically
      hindered, leading to a 13-fold decrease in the intrinsic affinity of an operator
      site for repressor, once the other site had been occupied. To assess the role of
      each operator in vivo, rafA was used as a reporter gene. A 1200-fold repression
      (100%) was exerted by RafR binding to the native O1O2 configuration, whereas O2
      alone exerted 45% and O1 alone 6% repression of rafA transcription. The
      differential effects of O1 versus O2 on transcription (despite matching
      affinities of O1 and O2 for repressor) suggest that positioning of the O2
      repressor complex between the -35 and -10 signals is crucial for transcription
      control and that repressor binding to the upstream O1 serves to enhance this
      effect.

PMID- 8277950
TI  - Effects of diets high in sucrose or aspartame on the behavior and cognitive
      performance of children.
AB  - BACKGROUND: Both dietary sucrose and the sweetener aspartame have been reported
      to produce hyperactivity and other behavioral problems in children. METHODS: We
      conducted a double-blind controlled trial with two groups of children: 25 normal
      preschool children (3 to 5 years of age), and 23 school-age children (6 to 10
      years) described by their parents as sensitive to sugar. The children and their
      families followed a different diet for each of three consecutive three-week
      periods. One diet was high in sucrose with no artificial sweeteners, another was
      low in sucrose and contained aspartame as a sweetener, and the third was low in
      sucrose and contained saccharin (placebo) as a sweetener. All the diets were
      essentially free of additives, artificial food coloring, and preservatives. The
      children's behavior and cognitive performance were evaluated weekly. RESULTS: The
      preschool children ingested a mean (+/- SD) of 5600 +/- 2100 mg of sucrose per
      kilogram of body weight per day while on the sucrose diet, 38 +/- 13 mg of
      aspartame per kilogram per day while on the aspartame diet, and 12 +/- 4.5 mg of
      saccharin per kilogram per day while on the saccharin diet. The school-age
      children considered to be sensitive to sugar ingested 4500 +/- 1200 mg of sucrose
      per kilogram, 32 +/- 8.9 mg of aspartame per kilogram, and 9.9 +/- 3.9 mg of
      saccharin per kilogram, respectively. For the children described as sugar
      sensitive, there were no significant differences among the three diets in any of
      39 behavioral and cognitive variables. For the preschool children, only 4 of the
      31 measures differed significantly among the three diets, and there was no
      consistent pattern in the differences that were observed. CONCLUSIONS: Even when
      intake exceeds typical dietary levels, neither dietary sucrose nor aspartame
      affects children's behavior or cognitive function.

PMID- 8277951
TI  - Islet amyloid polypeptide in patients with pancreatic cancer and diabetes.
AB  - BACKGROUND: The diabetes mellitus that occurs in patients with pancreatic cancer
      is characterized by marked insulin resistance that declines after tumor
      resection. Islet amyloid polypeptide (IAPP), a hormonal factor secreted from the
      pancreatic beta cells, reduces insulin sensitivity in vivo and glycogen synthesis
      in vitro. In this study, we examined the relation between IAPP and diabetes in
      patients with pancreatic cancer. METHODS: We measured IAPP in plasma from 30
      patients with pancreatic cancer, 46 patients with other cancers, 23 patients with
      diabetes, and 25 normal subjects. IAPP immunoreactivity and IAPP messenger RNA
      were studied in pancreatic cancers, pancreatic tissue adjacent to cancers, and
      normal pancreatic tissue. RESULTS: Plasma IAPP concentrations were elevated in
      the patients with pancreatic cancer as compared with the normal subjects (mean
      [+/- SD], 22.3 +/- 13.6 vs. 8.0 +/- 5.0 pmol per liter; P < 0.001), normal in the
      patients with other cancers, and normal or low in the patients with diabetes.
      Among the patients with pancreatic cancer, the concentrations were 25.0 +/- 8.7
      pmol per liter in the 7 patients with diabetes who required insulin, 31.4 +/-
      12.6 pmol per liter in the 11 patients with diabetes who did not require insulin,
      and 12.2 +/- 2.4 pmol per liter in the 9 patients with normal glucose tolerance
      (3 patients had impaired glucose tolerance; their mean plasma IAPP concentration
      was 11.7 +/- 5.5 pmol per liter). Plasma IAPP concentrations decreased after
      surgery in the seven patients with pancreatic cancer who were studied before and
      after subtotal pancreatectomy (28.9 +/- 16.4 vs. 5.6 +/- 3.4 pmol per liter, P =
      0.01). Pancreatic cancers contained IAPP, but the concentrations were lower than
      in normal pancreatic tissue (17 +/- 16 vs. 183 +/- 129 pmol per gram, P < 0.001).
      In samples from the patients with both pancreatic cancer and diabetes,
      immunostaining for IAPP was reduced in islets of pancreatic tissue surrounding
      the tumor; in situ hybridization studies suggested that transcription occurred
      normally in these islets. CONCLUSIONS: Plasma IAPP concentrations are elevated in
      patients with pancreatic cancer who have diabetes. Since IAPP may cause insulin
      resistance, its overproduction may contribute to the diabetes that occurs in
      these patients.

PMID- 8277952
TI  - Images in clinical medicine. Spontaneous human erythrocyte rosette.

PMID- 8277953
TI  - Adolescents and children injured or killed in drive-by shootings in Los Angeles.
AB  - BACKGROUND: Drive-by shootings by violent street gangs contribute to early
      morbidity and mortality among adolescents and children in Los Angeles. This study
      attempted to determine the frequency of this problem and the population at
      greatest risk. We also studied the most frequently injured areas of the body, the
      seasons in which the most shootings occurred, the most common sites for drive-by
      shootings, and the types of firearms used. METHODS: We retrospectively reviewed
      the files of the Gang Information Section of the Los Angeles Police Department to
      identify all drive-by shootings in Los Angeles in 1991 in which a child or
      adolescent under the age of 18 was shot at, injured, or killed. RESULTS: A total
      of 677 adolescents and children were shot at, among whom 429 (63 percent) had
      gunshot wounds and 36 (5.3 percent) died from their injuries. Three hundred three
      of those with gunshot wounds (71 percent) were gang members. Arms and legs were
      the areas of the body most commonly injured. Handguns were the most frequently
      used type of firearm. All the homicide victims were African American or Hispanic,
      and 97 percent were boys. African American and Hispanic children and adolescents,
      especially male gang members, had a significantly higher risk than their Asian
      and white counterparts of injury and death from drive-by shootings in Los Angeles
      (P < 0.001). CONCLUSIONS: Drive-by shootings involving adolescents and children
      are frequent in Los Angeles. Although Los Angeles may be an atypical case,
      understanding why violent street gangs form, preventing causes of violence, and
      limiting access to firearms are essential steps in preventing this serious
      problem.

PMID- 8277954
TI  - The molecular basis of leukemia.

PMID- 8277955
TI  - Care of patients with ascites.

PMID- 8277956
TI  - Saved by a test result.

PMID- 8277957
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 5-1994. A 34-year-old woman with mild exertional dyspnea and
      interstitial pulmonary lesions.

PMID- 8277958
TI  - Sugar and the hyperactive child.

PMID- 8277959
TI  - Our current approach to drug abuse--progress, problems, proposals.

PMID- 8277960
TI  - Guns and homicide in the home.

PMID- 8277961
TI  - Guns and homicide in the home.

PMID- 8277962
TI  - Guns and homicide in the home.

PMID- 8277963
TI  - Guns and homicide in the home.

PMID- 8277964
TI  - Guns and homicide in the home.

PMID- 8277965
TI  - Guns and homicide in the home.

PMID- 8277966
TI  - Guns and homicide in the home.

PMID- 8277967
TI  - Guns and homicide in the home.

PMID- 8277968
TI  - X-linked dilated cardiomyopathy.

PMID- 8277969
TI  - X-linked dilated cardiomyopathy.

PMID- 8277970
TI  - Cat scratch disease.

PMID- 8277971
TI  - Q fever during pregnancy--a risk for women, fetuses, and obstetricians.

PMID- 8277972
TI  - Renal transplantation in a noncompliant patient.

PMID- 8277973
TI  - Detention of HIV-positive Haitians and Cubans.

PMID- 8277974
TI  - ATP and endogenous agonists inhibit evoked [3H]-noradrenaline release in rat iris
      via A1 and P2y-like purinoceptors.
AB  - Effects of ATP, adenosine and purinoceptor antagonists on field stimulation
      evoked (3 Hz, 2 min) [3H]-noradrenaline overflow were investigated in the rat
      isolated iris. ATP and adenosine inhibited the evoked overflow of [3H]
      noradrenaline. 1,3-Dipropyl-8-cyclopentylxanthine (DPCPX) shifted the
      concentration-response curve of ATP to the right in a concentration-dependent
      manner, but with a potency (-log KB = 7.88) much lower than expected for an A1
      adenosine receptor. In the continuous presence of DPCPX, the ATP-induced
      prejunctional inhibition was unaffected by suramin (100 mumol/l) and DIDS (4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, 50 mumol/l) but was antagonized by
      the P2Y-receptor antagonist cibacron blue (= reactive blue 2; 30 and 100 mumol/l,
      -log KB = 4.7) and alpha,beta-methylene-ATP (10 mumol/l). Whereas the evoked [3H]
      noradrenaline overflow was unaffected by suramin and DIDS, cibacron blue and
      alpha,beta-methylene-ATP caused a small and transient increase. Cibacron blue at
      30 mumol/l failed to antagonize the inhibition of evoked [3H]-noradrenaline
      overflow that adenosine produced in the absence of DPCPX. Basal [3H]
      noradrenaline overflow was enhanced by cibacron blue, not changed by alpha,beta
      methylene-ATP and DIDS, and decreased by suramin. The results show that exogenous
      ATP inhibits sympathetic neurotransmission in the rat iris via A1 and P2Y-like
      purinoceptors. The latter have a low apparent affinity for cibacron blue and
      probably are blocked by alpha,beta-methylene-ATP. Under the present conditions,
      endogenous purines exert a tonic inhibition not only via A1- but also via these
      P2Y-receptors.

PMID- 8277975
TI  - Facilitatory and inhibitory modulation by endogenous adenosine of noradrenaline
      release in the epididymal portion of rat vas deferens.
AB  - The present study aimed at determining the modulation by adenosine of the release
      of noradrenaline in the epididymal portion of the rat vas deferens. The tissues
      were treated with pargyline and perifused in the presence of desipramine and
      yohimbine. Up to four periods of electrical stimulation were applied (5 Hz, 9
      min). The A1-adenosine receptor selective agonist R-N6-phenylisopropyladenosine
      (R-PIA; 100-900 nmol.l-1) reduced, whereas the A2A-receptor selective agonist 2-p
      (2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680; 3-30
      nmol.l-1) increased the electrically-evoked noradrenaline overflow in a
      concentration-dependent manner. The nonselective agonist 5'-N
      ethylcarboxamidoadenosine (NECA; 30-300 nmol.l-1) reduced noradrenaline overflow,
      but the effect did not depend on the concentration. Adenosine deaminase at the
      concentration of 0.5 mu.ml-1 decreased but at that of 2.0 mu.ml-1 increased
      noradrenaline overflow. The inhibitors of adenosine uptake, S-(4-nitrobenzyl)-6
      thioinosine (NBTI; 50 nmol.l-1) and dipyridamole (3 mumol.l-1), increased the
      electrically-evoked noradrenaline overflow. The A1-adenosine receptor antagonist
      1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 20 nmol.l-1) caused an increase
      whereas the A2-adenosine receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine
      (DMPX; 0.1 mumol.l-1) caused a decrease. NBTI (50 nmol.l-1), partially
      antagonized the effect of both DPCPX (20 nmol.l-1) and DMPX (0.1 mumol.l
      1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277976
TI  - Endothelin receptors in the human coronary artery, ventricle and atrium. A
      quantitative autoradiographic analysis.
AB  - In the present experiments we investigated endothelin (ET) receptors in the human
      coronary artery, and in ventricular and atrial muscle using quantitative receptor
      autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and
      [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor
      selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D-Val-L-Leu-D-Trp-]), and the ETB
      receptor selective ligand [Ala1, 3, 11, 15]ET-1. Specific binding was more dense
      in atrium and coronary artery (relative optical density (r.o.d.): 0.14 +/- 0.01
      and 0.16 +/- 0.01, respectively) than in ventricular muscle (r.o.d.: 0.10 +/-
      0.01). In the coronary artery, binding was especially dense in the media. ET-1
      displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and
      coronary artery. [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1 and
      [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the
      human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled
      sites monophasically (pIC50: ET-1 (9.72 +/- 0.12) > BQ-123 (6.84 +/- 0.08) >
      [Ala1,3,11,15]ET-1 (6.40 +/- 0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123
      displaced [125I]Sf6b-labeled coronary artery sites biphasically (high affinity
      pIC50: BQ-123, 9.03 +/- 0.25; [Ala1,3,11,15]ET-1, 8.40 +/- 0.14; low affinity
      pIC50: BQ-123, 7.24 +/- 0.14; [Ala1,3,11,15]ET-1, 6.99 +/- 0.09). These data
      indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites
      in human ventricular and atrial muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8277977
TI  - Inhibitory effects of cicletanine on smooth muscle in comparison to those of
      nifedipine and sodium nitroprusside.
AB  - The inhibitory effect of cicletanine was studied, in comparison to the effects of
      nifedipine and sodium nitroprusside (SNP), in various types of smooth muscle:
      portal vein and iliac artery of rabbit; gastric fundus and antrum of rabbit and
      guinea pig; guinea pig taenia coli and uterus. In all types of tissue the
      nifedipine-sensitive component (LCA, L-type calcium channel dependent activation)
      was inhibited by cicletanine (threshold concentration 10(-6) mol/l to 10(-5)
      mol/l). The nifedipine to resistant component (NLCA) was in some tissues
      preferentially inhibited by SNP (gastric fundus) and in other tissues
      preferentially by cicletanine (portal vein), with graded intermediate forms
      (iliac artery). Consequently, the inhibitory effect of cicletanine on NLCA is
      different in mechanism to that of SNP. Only papaverine suppressed all types of
      activation.

PMID- 8277978
TI  - NG-nitro L-arginine methyl ester: systemic and pulmonary haemodynamics, tissue
      blood flow and arteriovenous shunting in the pig.
AB  - The effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the
      endothelial nitric oxide (NO) biosynthesis, on systemic and pulmonary
      haemodynamics, and tissue as well as arteriovenous anastomotic blood flows were
      investigated in the anaesthetized pig, using simultaneous injections of
      radioactive microspheres of two different sizes (diameter: 15 and 50 microns). L
      NAME (1, 3 and 10 mg.kg-1) reduced systemic and pulmonary artery conductance and
      cardiac output, but heart rate and mean arterial blood pressure remained
      unchanged. L-arginine reversed the systemic and pulmonary haemodynamic changes
      induced by L-NAME. As detected with 15 microns microspheres, L-NAME (1 and 3
      mg.kg-1) decreased tissue blood flow to and vascular conductance in the eyes,
      lungs, atria, kidneys, adrenals and liver. Furthermore, the difference between
      blood flows simultaneously measured with 15 and 50 microns microspheres, which
      can be equated to blood flow through arteriovenous anastomoses with a diameter
      between about 28 and 90 microns, was reduced by L-NAME (3 mg.kg-1) in the skin of
      head and gluteal regions and, as indicated by the microsphere content of the
      lungs, in the total systemic circulation. These results suggest that in the
      anaesthetized pig (i) NO is involved in the regulation of both systemic and
      pulmonary vascular conductance, (ii) the decrease in systemic vascular
      conductance is in part due to constriction of systemic arteriovenous anastomoses,
      and (iii) the decrease in pulmonary vascular conductance, leading to reduction of
      cardiac output, seems to negate the expected rise in arterial blood pressure
      observed, for example, in rats and rabbits following inhibition of NO-synthesis.

PMID- 8277979
TI  - Response of mouse liver coumarin 7-hydroxylase activity to hepatotoxins:
      dependence on strain and agent and comparison to other monooxygenases.
AB  - Acute effects of a single intraperitoneal dose of allyl alcohol (AA, 64 mg/kg),
      dimethylnitrosamine (DMNA, 30 mg/kg), hexachlorobutadiene (HCBD, 50 mg/kg),
      carbon tetrachloride (CCl4, 24 mg/kg), cocaine (60 mg/kg) and pyrazole (300
      mg/kg) on the hepatic histology and monooxygenases in DBA/2 and C57Bl/6 strains
      of mice were investigated. All substances caused histologically verified injury
      to the liver, which varied in appearance and severity depending on the compound
      and the mouse strain. Responses of P450-catalyzed reactions were highly dependent
      on the toxin and varied between different monooxygenase (MO) reactions and two
      mouse strains. In DBA/2 strain, coumarin 7-hydroxylase (COH) activity was
      increased from 3- to 5-fold by pyrazole, cocaine, HCBD and CCl4. With respect to
      P450 content and other MO activities, no changes or even decreases were generally
      observed. Some exceptions to this rule were found: HCBD significantly increased
      T15 alpha OH, PROD and EROD activities in C57Bl/6 mice, whereas cocaine caused a
      significant stimulation of T15 alpha OH and PROD in DBA/2 mice, It is concluded
      that i) different hepatoxins cause different types of liver injury and responses
      of the monooxygenase complex ("hepatotoxinspecific finger prints"), ii) although
      DBA/2 and C57Bl/6 mice responded rather similarly to hepatotoxins, also with
      respect to P450 content and most MO activities, they displayed a profound
      difference in the behaviour of COH activity, and iii) within the P450
      superfamily, the regulation of COH activity seems to be rather unique, also when
      compared to its structurally close enzyme, testosterone 15 alpha-hydroxylase.

PMID- 8277980
TI  - [Rupture of the pregnant uterus].

PMID- 8277981
TI  - [Health problems following severe prematurity; 9-year follow-up study].

PMID- 8277982
TI  - [Treatment of adrenal cortex carcinoma].

PMID- 8277983
TI  - [Allergy for laboratory animals as occupational disease: clinical and
      occupational health aspects].

PMID- 8277984
TI  - [Hepatitis B in children in 4 university centers in The Netherlands].
AB  - OBJECTIVE: To evaluate the prevalence and the natural course of hepatitis B
      infection in children. DESIGN: Retrospective longitudinal. SETTING: Four
      university pediatric centres. METHOD: To explore the possibility of starting a
      trial with interferon alpha, data of viral and biochemical tests and biopsies of
      children younger than 16 years were studied. RESULTS: In a period of 10 years
      (1980-1990) 145 patients, of whom 74% were not of original Dutch descent, were
      found positive for HBsAg. The data of 142 patients could be analysed.
      Seroconversion was seen in 27 patients and 42 were already anti-HBe positive at
      the time of presentation. Chronic hepatitis, representing the category which
      could benefit from interferon alpha treatment, was found in 24 patients. Severe
      complications of the hepatitis were found in 4% of the children, including
      hepatocellular carcinoma and cirrhosis. Follow-up was insufficient so the
      seroconversion rate could only be estimated at 12% for the first year following
      the diagnosis. CONCLUSION: As a result of this study the authors present a
      proposal for a therapeutic trial with interferon alpha. This is a national
      protocol under the auspices of the section for pediatric gastroenterology of the
      Nederlandse Vereniging voor Kindergeneeskunde (Netherlands Pediatric
      Association).

PMID- 8277985
TI  - [Evaluation of the hepatitis B prevention program in newborn infants. I. National
      data, 1990].
AB  - OBJECTIVE: To evaluate the effectiveness of the national programme for prevention
      of perinatal hepatitis B infections. SETTING: The regional public health
      laboratories and provincial immunization administrations in the Netherlands.
      DESIGN: Retrospective evaluation. METHODS: Starting October 1989 routine
      screening of pregnant women for HBsAg was performed and passive-active
      immunisation of infants of HBsAg-positive mothers was added to the national
      immunisation programme. Infants receive hepatitis B immunoglobulin at birth and
      hepatitis B vaccine at 3,4,5, and 11 months of age, concomitant with the DTP
      polio vaccine. The effectiveness of screening and intervention in 1990 was
      evaluated. RESULTS: Screening covered about 85% of the pregnant population and
      the prevalence (0.44%) was less than expected. About 60% of the infants born to
      HBsAg-positive mothers were registered for vaccination. Of these infants the
      average coverage was 83% for immunoglobulin, and 90%, 86%, 80% and 55% for the
      four successive hepatitis B vaccinations. There was considerable delay in vaccine
      administration; frequently doses were administered later than recommended.
      CONCLUSION: Compliance with screening and vaccination appeared incomplete.
      Recommendations for the simplification of the current programme are made.

PMID- 8277986
TI  - [Evaluation of the hepatitis B prevention program in newborn infants. II.
      Amsterdam, 1989-1991].
AB  - OBJECTIVE: To evaluate the efficiency of the hepatitis B surface antigen (HBsAg)
      screening programme in pregnant women and the hepatitis B prevention programme in
      neonates of HBsAg-positive mothers from October 1989 to December 1991. DESIGN:
      Retrospective. SETTING: Amsterdam Public Health Service, the Netherlands. METHOD:
      Analysis of the data routinely collected from pregnant women and neonates of
      these women and calculation of the protective efficiency of this immunisation
      programme. RESULTS: In 1990, 79% and in 1991, 91% of all pregnant women were
      screened for HBsAg. The overall prevalence was 1.2% in 1990 as in 1991. Of the
      HBsAg-positive women 96% originated from countries where hepatitis B virus (HBV)
      is known to be endemic. At the age of ten months all infants had received passive
      and active immunisation. The anti-HBs titre was 10-50 IU/l in 8 (7%) infants, >
      50 IU/l in 94 (88%), 3 were HBsAg-negative with no information on the anti-HBs
      titre and in 2 HBsAg was present. The protective efficiency of the immunisation
      schedule was 94% in children born of e-antigen-positive and 93% in children born
      of e-antigen-negative mothers. CONCLUSION: Active surveillance and intense follow
      up are essential in achieving high coverage rates in screening of pregnant women
      and in immunising neonates of HBsAg-positive mothers.

PMID- 8277987
TI  - [The course of hepatitis B in 9 children who became positive for viral surface
      antigen HBsAg in spite of vaccination].
AB  - OBJECTIVE: To describe the viral, clinical and biochemical course of infants,
      who, in spite of passive-active hepatitis B immunisation, became infected with
      hepatitis B. DESIGN: Prospective cohort study. SETTING: The Netherlands. MATERIAL
      AND METHOD: As part of the research programme of the Dutch study group
      'Prevention neonatal hepatitis B', 705 newborns of HBsAg-positive mothers
      received passive and active immunisation. Despite passive-active immunisation, 9
      children became positive for HBsAg. These children were analysed clinically and
      their HBsAg, anti-HBs, HBeAg, anti-HBc and anti HD were measured. RESULTS: Median
      follow up was 5 years (range 3-8 years). Of the 9 HBsAg-positive infants 8 also
      tested positive for HBeAg. At the end of the follow-up 1 child had lost HBsAg and
      2 children had lost HBeAg. Only 1 child experienced a symptomatic hepatitis B
      infection with raised aminotransferase levels. The other 8 infants with chronic
      hepatitis B had no clinical symptoms. Aminotransferase levels were normal
      throughout in 7 infants. CONCLUSION: Most of the infants who, in spite of passive
      active hepatitis B immunisation, became HBsAg positive developed a chronic
      hepatitis B infection without clinical or biochemical dysfunctions. On the basis
      of these findings and considering possible therapy, guidelines are given for the
      follow up of children with chronic hepatitis B.

PMID- 8277989
TI  - [Financing of health research. Sound personnel management or quicksand?].

PMID- 8277988
TI  - [Elsberg syndrome: acute urinary retention following a viral infection].
AB  - In two patients, women, aged 32 and 30 years respectively, acute urinary
      retention after a viral infection was diagnosed. This is known as the Elsberg
      syndrome: urinary retention as a result of sacral myeloradiculitis. One of the
      patients had a blank history, the other suffered from a genital herpes infection.
      They were catheterised and instructed to perform catheterisation themselves. One
      was given an indwelling catheter. In the literature the Elsberg syndrome is
      mentioned relatively often after a genital herpetic infection. The treatment
      consists in (self)catheterisation. There may be hypesthesia in the sacral
      dermatomes. There is a strong tendency to recovering of spontaneous micturition
      in four to ten days.

PMID- 8277990
TI  - [Obstruction ileus with leg pain: consider an obturator hernia].

PMID- 8277991
TI  - [Cell and disease. III. Apoptosis, the biological opposite of mitosis].

PMID- 8277993
TI  - [Spasm after awakening; harmless?].

PMID- 8277992
TI  - [Treatment of liver metastases of colorectal tumors using intra-arterial
      fluorouracil to the liver, administered with a completely implantable access
      system and a portable infusion pump].

PMID- 8277994
TI  - [Charcot and Brown-Sequard; the controversy about cerebral localization].

PMID- 8277995
TI  - [Andreas Vesalius' 'De Humani Corporis Fabrica Libra Septem' 450 years].

PMID- 8277996
TI  - [The painting 'The anatomical lesson by Professor Louis Bolk' by Martin
      Monnickendam].
AB  - In 1992 the painting 'The anatomy of professor Louis Bolk' by the Dutch painter
      Martin Monnickendam (1874-1943), was finally returned to its place in the 'Tulp
      room' of the Department of Anatomy and Embryology at the University of Amsterdam,
      after the department had been moved to new premises in 1985. The professor of
      anatomy at the University of Amsterdam, Louis Bolk, is seated in the middle
      surrounded by his, at that time, former pupils, from left to right: Boeke, Barge
      and van den Broek, authors of a Dutch textbook of anatomy. The four professors
      are gathered around a cadaver of an orang-utan, placed not on a dissection table
      but on a console. Bolk is facing the observer and holding a scalpel in one hand
      while steadying the animal's head with the other; he is ready to make an
      incision. In the back of the painting a bust of the 18th century anatomist Petrus
      Camper is visible. The four professors all wear a white coat over their suits.
      Bolk finishes this off with an artistic bow tie whilst the others use an ordinary
      necktie. The painting is signed in the left upper corner 'Martin Monnickendam
      1925'.

PMID- 8277997
TI  - [4 medieval hospitals in Northern France].

PMID- 8277998
TI  - [Poverty and ignorance: puerperal fever in the Amsterdamse Binnengasthuis in
      1845].
AB  - The 1845 annual report of the maternity ward of the Amsterdam Binnengasthuis
      gives an insight into the obstetric knowledge and developments at that time, with
      emphasis on puerperal fever. Since the introduction of clinical training of
      medical students in 1828, maternal mortality had risen from 2.6% to 9.0%. In the
      year reviewed, 1845, maternal mortality was 8.6%. The report concerns 395
      indigent and malnourished women. Rickets was frequent. Delivery, presentation of
      the children, complications, operative deliveries and outcome of the children are
      described. Perinatal mortality was 12.5%. In the original text, an impressive
      epidemic of puerperal fever in the first 4 months of the year is described. It
      also gives us an authentic insight into the views on the dissemination of
      puerperal fever, both the 'epidemic' (influence of cold weather etc.) and the
      'contagionistic' view (dissemination by miasmata: evaporations from the diseased
      women). C.B. Tilanus Sr. (professor of obstetrics), reacted tepidly to
      Semmelweis' discoveries.

PMID- 8277999
TI  - [Unexpected movements in a brain-dead patient].
AB  - In a brain-dead patient, a 42-year-old woman who went into a coma after a
      cervical foraminotomy, spinal automatisms were seen which cast doubt on the
      diagnosis of brain death. The procedure which was to lead to organ
      transplantation was seriously disturbed. In brain-dead patients spinal
      automatisms appear earlier and are more often present than deep tendon reflexes.
      Due to the developing hyperreflexia spinal automatisms can be elicited more
      easily and from a larger skin area as the period of brain death lasts longer.
      Spinal automatisms can also appear spontaneously and can be generated by
      hypercapnia. If criteria for brain death are met, these movements are no reason
      to reconsider the diagnosis of brain death.

PMID- 8278000
TI  - [Neurogenic muscle hypertrophy].
AB  - Enlargement of the calf usually is associated with venous thrombosis,
      haemorrhage, focal myositis or a tumour in bone or muscle. Occasionally a calf
      enlargement is due to isolated muscle hypertrophy as a sign of radicular or
      peripheral nerve injury. Most neurogenic muscle hypertrophy is confined to the
      calf muscle, but the phenomenon has also been seen in other muscles. Three
      patients with S-I radiculopathy leading to ipsilateral neurogenic calf
      hypertrophy following hernia nuclei pulposi are described, two men of 79 and 78
      years old and a woman of 46 years. The symptoms gradually subsided with time and
      conservative treatment. The pathogenesis of neurogenic muscle hypertrophy
      possibly involves partial denervation atrophy and compensatory hypertrophy of
      remaining muscle fibres.

PMID- 8278001
TI  - [Scratch artifacts on the back; scientific research with reference to an
      advertisement].

PMID- 8278002
TI  - [Coincidence and chaos in medicine].

PMID- 8278003
TI  - [Sign language of the Middle Ages].

PMID- 8278004
TI  - [No benefit in the addition of dipyridamole to, nor of anticoagulants in
      comparison to, a low dose of acetylsalicylic acid (50 mg) in the prevention of
      venous transplant stenosis following coronary bypass surgery].

PMID- 8278005
TI  - [Strongyloides stercoralis: an insidious oddity].

PMID- 8278006
TI  - [Strongyloides stercoralis: an insidious oddity].

PMID- 8278007
TI  - [Ovum donation: is the shortage past? Ethical considerations].

PMID- 8278008
TI  - [A nurse with a hernia nuclei pulposi].

PMID- 8278009
TI  - [History of electroconvulsive therapy in the United States in the last decades].
AB  - Despite its acknowledged efficacy and safety in the treatment of patients with
      severe affective and psychotic illnesses, as well as extensive efforts at
      professional and public education, electroconvulsive therapy is a neglected
      treatment, its use in the U.S. being mainly restricted to academic and private
      hospitals. Widespread use between 1935 and 1960, a rapid decline following the
      introduction of psychoactive drugs, and a slow resurgence in clinical interest
      since 1975 characterizes its history. The use of ECT has been encouraged by
      repeated favorable evaluations and by new procedures which improve both its
      efficacy and its safety. The experience in the United States provides a lesson
      for other nations where its use is inhibited.

PMID- 8278010
TI  - [Analytic therapy of psychoses from a new viewpoint].

PMID- 8278011
TI  - [A chapter in systematic schizophrenia research--the search for causal
      explanations for sex differences in age of onset].
AB  - With the aim of detecting causal processes contributing to the onset of
      schizophrenic symptoms a systematic search strategy was worked out. One of the
      few epidemiological findings on schizophrenia consistently diverging from
      expected values, the sex difference in age at first admission, was taken as a
      basis and replicated on data from the Danish and the Mannheim case registers by
      controlling for selection and diagnostic artefacts. Danish psychiatrists turned
      out to have underdiagnosed schizophrenia to a considerable extent at least in
      1976, the year from which the analysed case-register data dated. After the
      exclusion of alternative explanations, the time when symptoms appeared for the
      first time and the first acute episode occurred was determined for a
      representative sample of 267 first-admitted cases with a diagnosis of non
      affective functional disorder by using the IRAOS interview designed for this
      purpose. At any of the definitions of first onset applied the mean age of females
      was significantly higher than that of males, the difference ranging from 3.2 to
      4.1 years. The distribution of onsets across the female life cycle showed a
      clearly delayed increase at young age and a second, lower peak of onsets at the
      age of 45-54, whereas the cumulative incidence up to the age of 60 years was
      equal for males and females. On assessing the plausibility of psychosocial versus
      biological explanations it was hypothesized that due to the effect of estrogens
      the vulnerability threshold for schizophrenia is raised in females until the
      menopause. Animal experiments and postmortem analysis showed that chronic
      estrogen applications significantly shortened dopamine-induced behaviour and
      reduced D2 receptor sensitivity in the brain. The applicability of this
      pathophysiological mechanism on human schizophrenia was tested on acutely
      schizophrenic females with normal menstrual cycles. A significant negative
      correlation was found between measures of symptomatology and plasma estrogen
      levels. Apparently, the manifestation of schizophrenic symptoms is influenced by
      a sufficiently sensitive D2 receptor system in the brain, blocked by neuroleptics
      and modulated by estrogens.

PMID- 8278012
TI  - [Clinical validity of the Beck Depression Inventory. A facet theoretical re
      analysis of multicenter clinical observations].
AB  - The items of the Beck Depression Inventory are reanalyzed by a non-metric
      multidimensional scaling procedure (Smallest Space Analysis, SSA-I). The
      structure of the test items is characterized within the framework of Guttman's
      facet theory. Two systematic components (facets) are discerned: "centrality" and
      "aspect". Properties of the facets as well as their relations are assessed and
      examined empirically by analyzing the interrelations among the items. The spatial
      configurations obtained by the scaling procedure fit the expectations derived
      from the facet-theoretic model. The facet "centrality" was found to have a strong
      overriding influence over the "aspect" facet. The results suggest the
      introduction of a new combination and selection of items reflecting different
      facets of depression consistently over time.

PMID- 8278013
TI  - ["Covert criticism"--a new criterion for determining the expressed emotion index
      in a five-minute speech sample of partners of depressed patients].
AB  - The expressed emotion (EE) index is a measure of affective attitudes held by
      relatives toward a mentally ill family member. In several studies it has been
      shown to be a predictor of relapse in the course of schizophrenia and depression.
      Since the Camberwell Family Interview (CFI) as the traditional method for
      assessing EE is time-consuming, a brief method--the Five-Minute Speech Sample
      (FMSS)--has been developed as an alternative for research and clinical work. The
      FMSS is also suitable for repeated application. Reliability and concurrent
      validity of the FMSS-EE have been demonstrated in cross-cultural samples of
      families with a schizophrenic member. However, application of the FMSS coding
      system to relatives of depressed patients in our sample proved to be problematic.
      Criticism, the most important EE-component, could not be assessed using the
      existing rating procedure. Therefore a modified version of the rating system has
      been developed. A new category named "covert criticism" has been defined which
      also includes indirect criticism. In an ongoing study a high degree of interrater
      reliability was achieved with the new system. Available data concerning
      concurrent validity indicate that clinically meaningful results can be derived by
      using the EE-ratings based on "covert criticism".

PMID- 8278014
TI  - [Anticonvulsant bromide therapy once and today].
AB  - During the past two decades, Bromides have undergone a renaissance as
      anticonvulsants. In this paper 6 indications for a modern bromide therapy are
      proposed. Guidelines referring to the concrete application of the drug, proposals
      concerning the dosage and any side effects are described. The present paper
      recalls the history of the first objectively effective treatment for confirmed
      epileptic syndromes and/or problems in the course of standard therapy
      (provocation of seizures, side effects, problematic interactions).

PMID- 8278015
TI  - [Progressive paralysis: prognostic indications by modern imaging procedures. A
      case report].
AB  - The case of a patient with early diagnosed neurosyphilis (general paresis) is
      presented. Modern neuroimaging techniques such as single photon emission computed
      tomography (SPECT) may give clues to the treatment outcome as early as 1 month
      after antibiotic treatment. Improvement of cognitive functions was accompanied by
      normalization of the initially altered P300-topography.

PMID- 8278016
TI  - [Pisa syndrome in clozapine therapy].
AB  - Neuroleptic therapy frequently induces undesirable extrapyramidal side effects.
      The Pisa syndrome is a rare extrapyramidal side effect caused by neuroleptic
      treatment. Twisting and bending to one side of the upper thorax, the neck and the
      head are its typical symptoms. These symptoms mainly develop in elderly patients
      with a history of neuroleptic treatment. To our knowledge there have been no
      reports of Pisa syndrome occurring during therapy with clozapine--an atypical
      neuroleptic drug with no major extrapyramidal side effects. We report on 4 female
      patients suffering from a chronic schizophrenic and/or depressive condition and
      having been on a long-term neuroleptic treatment. These patients developed a
      dystonia equivalent to the Pisa syndrome during an acute clozapine therapy. All
      four women had signs of marked brain atrophy, two of them also showing tardive
      dyskinesia already prior to the treatment with clozapine. The etiology of the
      Pisa syndrome is discussed with respect to discontinuation of treatment with
      classic neuroleptics, coinciding with the beginning of the clozapine therapy,
      clinical phenomenology, history of medication, course of treatment, and results
      of cranial computer tomography.

PMID- 8278017
TI  - [Pseudo-hallucinations after long-term lithium treatment].
AB  - A 58-year old women with a history of recurrent depressive episodes had been on
      successful prophylaxis with lithium carbonate in controlled therapeutic dosage
      for 11 years. At this time she experienced with increasing frequency mostly
      visual, sometimes auditory pseudohallucinations which disappeared after stopping
      the lithium medication. Because a subsequent depressive episode did not respond
      to tricyclic antidepressants or to a MAO-inhibitor the patient was again
      prescribed lithium. At therapeutic lithium blood levels the previous perceptual
      disorders then returned.

PMID- 8278018
TI  - [Early childhood form of negativistic catatonia. Comments on the contribution by
      E. Franzek et al].

PMID- 8278019
TI  - Leucotomized schizophrenics lose neurons in the mediodorsal thalamic nucleus.
AB  - It has previously been shown that chronic schizophrenic patients have a 40-50%
      reduction in the total number of nerve and glia cells in the mediodorsal thalamic
      nucleus and the nucleus accumbens compared with controls, while the total neuron
      and glia number is the same in the two groups in the ventral pallidum. Using new
      stereological cell counting methods, neuron and glia cell numbers were estimated
      in the mediodorsal thalamic nucleus, the ventro-medial part of nucleus accumbens
      and the ventral pallidum in nine brains from leucotomized schizophrenics. This
      number was compared with counts from control cases and chronic schizophrenics
      without leucotomy. The results showed that the total number of nerve cells in the
      mediodorsal thalamic nucleus was statistically significantly reduced from 1.08 x
      10(6) in chronic schizophrenics to 0.88 x 10(6) in leucotomized schizophrenics.
      Total neuron number was statistically significantly reduced in the ventro-medial
      part of the nucleus accumbens in schizophrenics without further reduction in
      leucotomized schizophrenics. The total neuron number in ventral pallidum was
      normal. With frontal leucotomy it is possible to investigate the consequences of
      disconnection of the prefrontal cortex to central regions in the human brain. The
      mediodorsal nucleus of thalamus represents a major efferent projection to the
      prefrontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278020
TI  - Selective excitotoxic pathology in the rat hippocampus.
AB  - The pattern of cell loss and neuronal degeneration resulting from multiple
      microinjections of N-methyl-D-aspartate (NMDA), ibotenate (IBO), quisqualate
      (QUIS), and kainate (KA) into hippocampus was studied, together with the
      protection provided by the NMDA antagonist 3-(+/-)-2-carboxypiperazin-4-yl-propyl
      1-phosphonate (CPP). Histological evaluation was carried out after 7 days of
      survival. NMDA and IBO resulted in an extensive loss of all cells in the
      hippocampus including dentate gyrus, hilar cells, and CA3-CA1 pyramidal cells,
      but there was an absence of damage to areas and structures outside hippocampus.
      After QUIS and KA injections the hippocampal damage was limited to hilar cells in
      the dentate gyrus, CA3 pyramidal cells, and partial loss of CA1 cells; there was
      extensive extrahippocampal damage including entorhinal cortex, amygdala, layers
      III, V, and VI of ventral neocortex, olfactory areas, and various thalamic
      nuclei. CPP provided almost complete protection from the effects of
      intrahippocampal injections of NMDA and IBO, but did not affect the hippocampal
      cell loss found after QUIS and KA (with the exception of minor protection of some
      CA1 cells). CPP protected most extrahippocampal sites from the damage resulting
      from QUIS and KA, indicating that such excitotoxic cell death is indirect and
      involves NMDA receptor activation by an endogenous agent. The use of multiple
      microinjections as opposed to single injections allows a clearer interpretation
      of selective excitotoxic vulnerability.

PMID- 8278021
TI  - Neuronophagia in the motor cortex in amyotrophic lateral sclerosis.
AB  - This study was designed to identify which phagocytic cells in the cerebral cortex
      of amyotrophic lateral sclerosis (ALS) patients are involved in the process of
      neuronophagia. For this purpose a number of single and double immunocytochemical
      stains were carried out on five ALS cases which were selected on the basis of the
      presence of degenerative and phagocytic phenomena in the cerebral cortex. The
      cortical degenerative process is mainly present in the third and fifth layers and
      is not restricted to the fifth layer which contains the cell bodies of the Betz
      cells. The present study indicates that a number of cells are involved in the
      process of phagocytosis in ALS. Resident macrophages (from microglial or
      perivascular origin) and astrocytes seem to play an immunologically-mediated role
      in the disappearance of neurons. Some of the cells involved in the degenerative
      process, i.e. rounded macrophages and microglia, expressed major
      histocompatibility class II antigen. The phagocytic cells in neuronophagia were
      phenotypically identical to perivascular macrophages and not to microglia.
      Therefore, the process of phagocytosis of neurons appears to be primarily the
      task of the perivascularly located macrophage.

PMID- 8278022
TI  - Cellular changes in the cerebellar granular layer in AIDS-associated PML.
AB  - Six cases of AIDS-associated progressive multifocal leukoencephalopathy (PML)
      exhibited peculiar cellular changes in the cerebellar granular layer. These cells
      without discernible cytoplasm showed hypochromatic nuclei about twice as large as
      those of normal granule cells. They were restricted exclusively to the granular
      layer and always surrounded PML foci. An astrocytic, leukocytic or
      macrophage/microglial nature was largely excluded by immunocytochemistry. Human
      immunodeficiency virus (HIV) antigen p 24 could not be found in these cells and
      there was no unequivocal detection of JC virus (JCV) DNA and no ultrastructural
      evidence of papovavirus particles in them. They possibly represent altered
      cerebellar granule cells abortively or latently infected with JCV.

PMID- 8278023
TI  - Neurological reactions in HIV-infected patients treated with trichosanthin.
AB  - Trichosanthin is a ribosome-inactivating protein that is being studied as a
      possible treatment for patients infected with human immunodeficiency virus (HIV).
      We report the clinical and pathological features in two patients who experienced
      neurological reactions to trichosanthin. Both patients were neurologically
      asymptomatic prior to treatment but developed coma and multifocal neurological
      deficits after treatment. Neuropathological examination revealed regions of
      severe, multifocal necrosis with histiocytic infiltrates. These reactions to
      trichosanthin may be mediated by soluble factors released by HIV-infected
      macrophages.

PMID- 8278024
TI  - Myopathy in HIV infection: the role of zidovudine and the significance of
      tubuloreticular inclusions.
AB  - Muscle biopsies were obtained from 33 consecutive HIV-infected patients with
      symptoms suggestive of muscle disorder. Twenty-three patients had clinical
      evidence of myopathy; 18 of these had been taking zidovudine (AZT) for between 8
      and 28 months, and were found to have a multifocal necrotizing myopathy with
      little or no inflammation. However, the remaining five clinically myopathic
      patients, who had never received AZT or had stopped treatment at least 5 months
      earlier, had either a necrotizing myopathy which appeared indistinguishable for
      that seen in patients taking the drug, or an inflammatory myopathy. The 10
      clinically non-myopathic patients showed no significant histological
      abnormalities. Tubuloreticular inclusions (TRI), in capillary endothelial cells,
      were found in all clinically myopathic cases but were not seen in five out of ten
      clinically non-myopathic cases. We suggest that AZT causes a myopathy only when
      an underlying HIV-related inflammatory myopathy is present. The drug appears to
      substantially reduce the inflammatory reaction in the muscle, but this may recur
      when the drug is stopped. The appearance of TRI may be the first manifestation of
      HIV activity in muscle.

PMID- 8278026
TI  - Immunocytochemical detection of the microsomal glucose-6-phosphatase in human
      brain astrocytes.
AB  - Using an antibody raised against the catalytic subunit of glucose-6-phosphatase,
      this enzyme was immunolocalized in many astrocytes in 20 normal human brains.
      Double immunofluorescence studies showed co-localization of glial fibrillary
      acidic protein (GFAP) with glucose-6-phosphatase in astrocytes. However, not all
      GFAP-positive cells were also glucose-6-phosphatase positive, indicating that
      some astrocytes do not contain demonstrable expression of this enzyme. Reactive
      astrocytes in a variety of abnormal brains were strongly glucose-6-phosphatase
      positive, but neoplastic astrocytes were often only weakly positive. Expression
      of the enzyme could not be demonstrated in radial glia, neurons or
      oligodendroglia. Astrocytes normally contain glycogen and the demonstration that
      some astrocytes also contain glucose-6-phosphatase indicates that they are
      competent for both glycogenolysis and gluconeogenesis, which may be critical for
      neuronal welfare.

PMID- 8278025
TI  - Mumps virus alters aggregation of acetylcholine receptors in cultured rat
      skeletal muscle cells.
AB  - Cultured myoblasts, but not myotubes, from rat skeletal muscles were infected
      with the RW strain of mumps virus. Such myoblasts then fused to form myotubes
      containing viral antigen. The infected myotubes showed a significant decrease in
      the number of dorsal, linear acetylcholine receptor (AChR) aggregates as
      determined by FITC-conjugated alfa-bungarotoxin. Infected myotubes co-cultivated
      with spinal cord cells showed no increase in the number of dorsal, linear AChR
      aggregates, compared to normal, uninfected myotubes. In addition, an increased
      proliferation of the myoblasts, which remained uninfected in the infected
      cultures, was noted. This may indicate a release of a growth stimulating factor
      from the virus containing cells. This study shows that mumps virus infection can
      lead to an altered receptor organization in a morphologically preserved cell.

PMID- 8278027
TI  - Comparative study on the expression of stress-response protein (srp) 72, srp 27,
      alpha B-crystallin and ubiquitin in brain tumours. An immunohistochemical
      investigation.
AB  - This immunohistochemical study compares the expression of stress-response (heat
      shock) protein (srp) 72, srp 27, alpha B-crystallin and ubiquitin in 86 primary
      human brain tumours and 21 carcinoma metastases to the central nervous system.
      Normal brain tissues were included for control purposes. Serial sections of
      formalin-fixed, paraffin-embedded tissues were used. Most meningiomas (17/23),
      glioblastomas (11/12) and breast carcinoma metastases (9/10) and some
      astrocytomas (7/13), pituitary tumours (4/9) and lung cancer metastases (5/11)
      had tumour cells that reacted with one or more of the antibodies used. Around 43%
      of the meningiomas and 25% of the glioblastomas expressed srp 72 only. Sole
      expression of srp 27, alpha B-crystallin or ubiquitin was seen in several
      tumours. Some meningiomas (3/23) and breast cancer metastases (4/10) co-expressed
      srp 72 and srp 27, and 1/3 of the glioblastomas co-expressed srp 27 and alpha B
      crystallin. We conclude that primary and metastatic tumours of the brain produce
      stress-related proteins and that certain tumours concurrently express two or more
      srp's.

PMID- 8278028
TI  - Introduction and history of the use of electroencephalography in animal drug
      studies.
AB  - A brief review of the development and the state-of-the-art of EEG methods used to
      study drug effects is presented. Classification systems based on drug effects in
      animals kept awake artificially, and based on drug effects on the sleep-wake
      state duration and distribution are discussed. It is concluded that the
      techniques are there and the time is ripe to develop animal EEG-based drug
      classification systems with high predictive ability.

PMID- 8278029
TI  - Computer-based prediction of psychotropic drug classes based on a discriminant
      analysis of drug effects on rat sleep.
AB  - The goal of the present study was to classify psychotropic drugs on the basis of
      EEG-defined rat sleep-waking behaviour. Using an automated sleep classification
      system it was found that some of the drug-induced changes in sleep-waking
      behaviour were specific for the pharmacotherapeutic treatment class to which the
      drug belonged. In several preliminary experiments we further found that drugs may
      have effects on rat EEG independent of their effects on rat sleep-waking
      behaviour and that these pharmaco-EEG effects may be different for the various
      sleep and waking stages. By analysing sleep class-independent EEG-spectral
      parameters a single drug effect score can, moreover, be obtained giving
      information on drug pharmacodynamics. The drug-induced changes in sleep-waking
      behaviour were used to classify a large number of drugs into several therapy
      classes by means of a discriminant analysis procedure. Antidepressants,
      antipsychotics and stimulants were discriminated successfully from each other and
      from placebo by this system, whereas nootropics classified as placebo.
      Anxiolytics, hypnotics and anticonvulsants classified poorly. Their
      classification is hampered by the lack of specific compounds. Assigned drug class
      and assignment probability were dose dependent. In the discussion of the present
      study it is suggested that animal pharmaco-sleep and pharmaco-EEG studies are not
      mutually exclusive approaches, but that they may complement each other.

PMID- 8278030
TI  - Cortical and subcortical EEG in relation to sleep-wake behavior in mammalian
      species.
AB  - In humans and several other mammals, a quantitative EEG analysis has been used to
      study the regulation of sleep-wake behavior. In all mammalian species studied,
      cortical EEG recorded during non-REM sleep (NREMS) is characterized by the
      occurrence of spindles and high voltage, slow waves (0.5-4.0 Hz). Furthermore,
      slow-wave activity (SWA) is low at the beginning of a NREM episode and it rises
      in the course of a NREM episode. The rise rate and the maximal level of SWA are a
      monotonic function of the duration of prior wakefulness. During REMS, cortical
      EEG typically exists of low-voltage, mixed frequencies and, in some animals, a
      prominent theta rhythm is superimposed. Only after sleep deprivation in some
      species does cortical EEG within REMS change. Especially, the EEG activity during
      wakefulness depends considerably on the behavioral state, on the electrode
      location and on the species. On average, cortical EEG within wakefulness consists
      of low-voltage, mixed frequencies. The few studies done on subcortical EEG
      clearly show that the electrical activity differs highly between brain regions
      and between species. However, two recent studies, in which a spectral analysis of
      subcortical EEG was made, showed that, at least in humans and cats, the changes
      occurring in subcortical EEG associated with changes in sleep-wake behavior
      parallel the general characteristics of cortical EEG described above.

PMID- 8278031
TI  - Classification of drugs based on visually evoked responses in rats.
AB  - Quantified parameters of photically evoked afterdischarge and EEG background
      activity of visual cortex of freely moving rats were used as variables to obtain
      a t profile for each drug dosage. Behavioural scores were also used. The
      determination of the dose/time-effect profile of a compound was based on
      normalization of data and on calculation of the first two factor values in
      comparison with pooled data of representatives of neuroleptic, anxiolytic,
      convulsant, petit mal anticonvulsant, antidepressant and psychostimulant drug
      classes. The compounds were investigated in different dosages and/or routes of
      administration. The model and procedure are validated for antipsychotic,
      anxiolytic and vigilance enhancer effect, and comprise the predictability of
      proconvulsive and petit mal anticonvulsive effects.

PMID- 8278032
TI  - Mycotic encephalitis: predilection for grey matter.
AB  - In mycotic infections of the brain three patterns of abnormality may be observed:
      meningitis, granuloma, and encephalitis. The first two, consisting of diffuse
      meningeal enhancement and mass lesion respectively, can easily be visualised by
      CT or MRI, but are nonspecific. The third pattern has been described
      histopathologically; as the clinical picture is nonspecific and the diagnosis is
      often unsuspected, especially in immunocompetent patients, acquaintance with the
      characteristic CT and MRI patterns of mycotic encephalitis may help in
      establishing the correct diagnosis, with important therapeutic consequences.

PMID- 8278033
TI  - The callosal-septal interface lesion in multiple sclerosis: effect of sequence
      and imaging plane.
AB  - We examined the effect of imaging plane and sequence on the demonstration of
      lesions at the callosal-septal interface (CSI) by magnetic resonance imaging in
      20 patients with known multiple sclerosis. Variable-echo-(VE) T2- and proton
      density (PD) weighted images were performed in coronal axial and sagittal planes.
      Sagittal gradient echo (GE) T2- and PD-weighted images were also performed.
      Lesions at the CSI were seen in all patients and were all demonstrated on both
      sagittal and coronal VE images. Sagittal PD-weighted GE images were slightly less
      sensitive but showed good overall agreement with sagittal VE. Axial VE and
      sagittal T2-weighted GE images demonstrated CSI lesions poorly.

PMID- 8278034
TI  - Balo's concentric sclerosis followed by MRI and positron emission tomography.
AB  - We report a case of Balo's concentric sclerosis diagnosed in vivo by
      characteristic MRI changes and stereotactic biopsy. Follow-up after 6 months of
      immunosuppressive treatment demonstrated virtually complete clinical remission,
      reduction of the white matter lesions on MRI and normalisation of regional
      cerebral glucose metabolism as assessed by positron emission tomography not only
      in white matter but also in the cerebral grey matter structures with input from
      the affected regions.

PMID- 8278035
TI  - MRI abnormalities in Creutzfeldt-Jakob disease.
AB  - Two patients with biopsy-proven Creutzfeldt-Jakob disease had MRI studies that
      revealed increased signal in the basal ganglia on T-2 weighted images, suggesting
      that MRI can be a useful diagnostic instrument in Creutzfeldt-Jakob disease.

PMID- 8278036
TI  - Asymptomatic postendarterectomy dissection of the internal carotid artery
      detected incidentally on MRI.
AB  - A patient who had recently undergone carotid endarterectomy was found to have
      internal carotid artery dissection on an MRI examination. This is a supposedly
      rare complication of this frequently performed operation. Since most patients
      with dissection of the ICA (from whatever cause) are symptomatic when the
      diagnosis is made, its incidental detection in an asymptomatic patient suggests
      that this complication may be commoner than generally recognised. We review the
      ways in which carotid dissection may occur during endarterectomy and the
      differential diagnosis of the MRI appearances.

PMID- 8278037
TI  - Agenesis of the internal carotid artery and cavernous sinus hypoplasia with
      contralateral cavernous sinus meningioma.

PMID- 8278038
TI  - CT in hanging.

PMID- 8278039
TI  - Spread of blood in cerebrospinal fluid following craniotomy simulates spinal
      metastases.
AB  - Postoperative myelography with water-soluble contrast media was performed in 36
      children with a diagnosis of posterior cranial fossa tumour. The myelograms were
      normal in 15. In 5 an intramedullary tumour was present and 3 of these had in
      addition subarachnoid changes as evidence of tumour spread. The remaining 16
      patient had subarachnoid changes of a different character, mainly located in the
      posterior thoracic region and similar to those seen after subarachnoid
      haemorrhage. It is suggested that they represent adhesions caused by blood from
      the operation. The blood is assumed to be distributed by the large cerebrospinal
      fluid pulsations to the cervical and thoracic regions. It is important to
      recognise and differentiate subarachnoid changes due to tumour and to
      postoperative adhesions to avoid unnecessary radiotherapy to the spinal cord.

PMID- 8278040
TI  - Cervical intervertebral foramen narrowing and myelographic nerve root sleeve
      deformities.
AB  - Intervertebral foramen narrowing on plain radiographs of the cervical spine was
      graded from 0 (normal) to 3 according to its severity; myelographic nerve root
      sleeve deformity was graded from 1 to 3 in 99 consecutive patients with cervical
      radiculopathy. We thus examined 1118 foramina and root sleeves. Plain radiographs
      of 684 foramina were normal, changes of one grade were seen in 243, of two grades
      in 145 and of three grades in 46. Grading of myelographic root sleeves' was
      normal in 789, changes of one grade in 157, of two grades in 129, and of three
      grades in 43. The correlations between the foraminal and root sleeve changes
      were: full correlation in 63.9%, a difference of one grade in 27.4%, a difference
      of two grades in 7.4% and a difference of three grades in 1.3%. The positive
      predictive value of the plain radiographs for myelographic root sleeve
      deformities was 55.5% and the negative value 87.1%.

PMID- 8278041
TI  - Arteriovenous malformation of the spinal cord mimicking a tumour.

PMID- 8278042
TI  - Intra-arterial fibrinolytic therapy in central retinal artery occlusion.
AB  - We have treated 23 patients with central retinal artery occlusion by intra
      arterial fibrinolysis, a method already in use for treatment of thromboembolic
      occlusion of the cerebral arteries. Fibrinolysis was carried out through a
      microcatheter placed in the origin of the ophthalmic artery. When ophthalmic
      artery cannot be catheterised, treatment can be carried out indirectly via the
      maxillary-ophthalmic anastomoses. In 18 cases urokinase was used in doses of
      200,000-1,200,000 units; in 5 patients recombinant tissue plasminogen activator
      was used. Six patients showed marked improvement or total recovery, and six
      partial recovery, with improvement of visual acuity or a field defect. The worst
      results were obtained in six patients where the mean delay between the appearance
      of symptoms and initiation of treatment was more than 20 h. Intra-arterial
      thrombolysis led to a better outcome in acute occlusion of the central retinal
      artery than might have been expected with conservative treatment. A good
      prognosis is to be expected when treatment starts within the first 6-8 h, when
      some vision remains and when there is less retinal oedema.

PMID- 8278044
TI  - Orbital "blow-in" fracture: MRI.
AB  - A case of traumatic orbital encephalocele following a "blow-in" fracture is
      presented. Computed tomography (CT) and magnetic resonance imaging (MRI) findings
      are shown. Although CT was useful for identifying the orbital roof fracture, bone
      fragments and soft tissue abnormalities, MRI was more sensitive to brain
      herniation and an intraorbital haematoma.

PMID- 8278043
TI  - Magnetic resonance tomographic angiography in the investigation of hemifacial
      spasm.
AB  - Magnetic resonance angiography (MRA), combined with submillimeter magnetic
      resonance tomographic angiographic sections (MRTA) showed vascular compression of
      the 7th cranial nerve or its root exit zone (REZ) in the brain stem in 24 of 37
      patients (64.86%) with hemifacial spasm. MRA alone was positive for REZ
      compression in only 19 (51.4%) cases, while conventional MRI was even less
      revealing, only 10 (27%) cases being positive.

PMID- 8278045
TI  - Neurofibroma: an unusual presentation.
AB  - We report neurofibroma discovered incidentally in a woman who suffered trauma to
      her cheek. The lesion was manifest on CT as a haematoma within a parotid tumour.

PMID- 8278046
TI  - Computed tomography of spontaneous intracranial haemorrhage due to haemostatic
      disorders in children.
AB  - Intracranial haemorrhage is a serious problem in haemostatic disorders in
      children. Intracranial bleeding is sometimes more marked than suspected
      clinically. Computed tomography (CT) permits accurate, sensitive diagnosis of
      intracranial haemorrhage. We report 13 patients; 3 patients with
      hypoprothrombinaemia, 4 patients with thrombocytopenia or platelet dysfunction
      and 6 with haemophilia A, B or Von-Willebrand's disease. One patient with
      hypoprothrombinaemia had a subarachnoid hemorrhage (SAH), one a subdural
      haematoma (SDH) and the third a combination of SAH, SDH and intracerebral
      haematoma (ICH). One patient with thrombocytopenia or platelet dysfunction had a
      SDH, while the others had ICH. In the six patients with haemophilia A, B or Von
      Willebrand's disease, there were four examples of ICH, five of SAH and six of
      SDH. A neurosurgical procedure was performed in only one patient. Three children
      died of serious intracranial complications with uncal herniation.

PMID- 8278047
TI  - Organization of the output of the ventral striatopallidal system in the rat:
      ventral pallidal efferents.
AB  - The efferent projections of the ventral pallidum in the rat were studied using
      anterograde tracing of Phaseolus vulgaris-leucoagglutinin and retrograde tracing
      of choleratoxin subunit B. The main aim of this study was to determine the degree
      of topographical organization in the outputs of the ventral pallidum. In the
      telencephalon, ventral pallidal fibers reach the prefrontal cortex, the ventral
      striatum, the lateral septum, the basolateral, lateral, and central amygdaloid
      nuclei, and the lateral entorhinal area. Diencephalic targets of ventral pallidal
      fibers are the lateral hypothalamus, the reticular nucleus of the thalamus, the
      mediodorsal thalamic nucleus, the dorsomedial part of the subthalamic nucleus,
      the medial part of the parafascicular nucleus and the lateral habenula. In the
      mesencephalon, ventral pallidal fibers terminate in the ventral tegmental area,
      the substantia nigra, the retrorubral area, the median raphe nucleus, the nucleus
      raphe magnus, the peribrachial area, the ventromedial part of the central gray
      substance and the locus coeruleus. The results of the experiments in which
      retrograde tracers were injected in different nuclei in the mesencephalon allow
      the distinction of two main areas in the ventral pallidum. Deposits of retrograde
      tracers in the substantia nigra, pars reticulata result in labeling of cells in
      the dorsolateral part of the ventral pallidum, located immediately ventral to the
      anterior limb of the anterior commissure. Retrograde tracer injections in other
      targets of the ventral mesencephalon, i.e. the dopaminergic cell groups A10, A9
      or A8, or nuclei in the peribrachial area result in labeling of neurons in an
      extensive ventromedial and ventrolateral zone of the ventral pallidum. The medial
      part of this ventral pallidal zone projects to the ventral tegmental area,
      whereas ventral and lateral parts connect with more lateral and caudal
      mesencephalic targets. The projections from the ventral pallidum to the ventral
      striatum, the subthalamic nucleus and adjacent lateral hypothalamic area, and the
      mediodorsal thalamic nucleus are distinctly topographically organized. The
      ventral pallidostriatal projections preserve a medial-to-lateral, a dorsal-to
      ventral and, to a lesser degree, a rostral-to-caudal topography. With respect to
      the subthalamic region, the dorsolateral part of the ventral pallidum projects to
      the dorsomedial part of the subthalamic nucleus, whereas the ventromedial and
      ventrolateral parts of the ventral pallidum are topographically connected with
      the area of the lateral hypothalamus medially adjacent to the subthalamic
      nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8278048
TI  - Expression of multiple alpha adrenergic receptor subtype messenger RNAs in the
      adult rat brain.
AB  - Multiple subtypes of alpha adrenergic receptors with CNS expression (alpha 1A,
      alpha 1B, alpha 2A and alpha 2C) have been identified through pharmacological and
      molecular biological means. To characterize the localization of these subtypes
      and attempt to correlate subtype expression with physiological significance, the
      expression of the mRNAs encoding the alpha 1A, alpha 1B, alpha 2A and alpha 2C
      adrenergic receptor subtypes was examined in the adult rat brain by in situ
      hybridization histochemistry. Each subtype demonstrated a unique pattern of
      distribution, with the alpha 1 adrenergic receptors more restricted in their
      distribution and the alpha 2 receptors more widespread. The alpha 1A was
      primarily localized in the olfactory bulb, intermediate layers of the cortex, the
      hippocampus and the reticular nucleus of the thalamus. The alpha 1B was expressed
      in intermediate and deep layers of the cortex, thalamus, hippocampus, dorsal
      raphe and cerebellum. Although the alpha 2A message was relatively low in
      abundance, it was identified in the olfactory bulb, cortex, hippocampus, locus
      coeruleus, pons and cerebellum. The alpha 2C messenger RNA was localized in the
      cortex (particularly cingulate), hippocampus, caudoputamen, pons and cerebellum.
      Multiple alpha adrenergic receptor subtypes have significant sequence homology
      and similar pharmacologic properties; however, they each possess a unique pattern
      of messenger RNA distribution throughout the brain. The multiplicity of subtypes
      of alpha adrenergic receptors in specific brain regions may dictate the
      physiological and pharmacological responses to catecholamines.

PMID- 8278049
TI  - Lumbosacral spinal neurons in the cat that are candidates for being activated by
      collaterals from the spinocervical tract.
AB  - Lumbosacral spinal neurons activated via the spinocervical tract were stained by
      intracellular injection of horseradish peroxidase in cats anaesthetized with
      chloralose and paralysed with gallamine triethiodide. The neurons were activated
      orthodromically by single shock stimulation of the ipsilateral dorsolateral
      funiculus at the second to third cervical segment, but not from the rostral part
      of the first cervical segment. Twenty nine cells were recovered from the
      histological material and subsequently reconstructed from transverse sections.
      Sixteen cells (55%) had axons that projected ipsilaterally to the lateral
      funiculus and their somata were located in two regions of the spinal cord, one
      group in the dorsal horn (laminae IV-V) and the other in the intermediate gray
      matter (laminae VI-VII). The axons of 10 of these cells gave off collaterals, and
      in seven of them the collaterals ramified in the grey matter deep to the cell
      body. The axons of five cells (17%) projected medially towards the central canal,
      four crossing the mid line in the ventral white commissure and ascending in the
      contralateral ventral funiculus. Only one of these cells had an axon collateral
      that crossed into the contralateral dorsal horn. Of the remaining eight cells,
      three had no obvious long axons but had many local axon collaterals, the axons of
      three cells were not stained, one had an axon projecting towards the ipsilateral
      ventral funiculus and one was a motoneuron and its axon projected into a ventral
      root. A feature of the dendritic trees of many cells was their wide spread in the
      mediolateral and/or the dorsoventral directions, although no dendrites reached
      dorsally into lamina II. Twenty-two cells (76%) were excited by moving hairs and
      by noxious pinch, three (10%) by hair movement alone, two (7%) by noxious pinch
      and pressure, and for two cells (7%) no receptive field could be found. It is
      concluded that not only postsynaptic dorsal column neurons receive input from the
      spinocervical tract but also other cells in the dorsal and ventral horns and the
      intermediate gray matter. Possible identities for these cells are discussed.

PMID- 8278050
TI  - Activity of deep dorsal horn neurons in the anaesthetized rat during hyperalgesia
      of the hindpaw induced by ultraviolet irradiation.
AB  - Thermal hyperalgesia was induced by UV irradiation of the glabrous skin of the
      hindpaw of adult female Sprague-Dawley rats. We have recorded single cell
      activity and studied excitability changes in wide dynamic range neurons in the
      lumbar spinal segments during the early phase (days 1-3) and late phase (days 5
      7) of thermal hyperalgesia in animals under urethane anaesthesia. The proportion
      of spontaneously active wide dynamic range cells was increased following UV
      irradiation and the degree of spontaneous activity was enhanced during the course
      of hyperalgesia. In addition there was a significant increase in the total number
      of spikes evoked by standardized mechanical and noxious heat stimuli when tested
      at days 1-3 and days 5-7. The duration of the evoked responses was also
      significantly prolonged in both UV-treated groups. The noxious temperature
      threshold to radiant heat stimulation was significantly decreased on the UV
      treated but not on the contralateral hindpaw. The average size of the receptive
      fields on the UV-treated paws was expanded in comparison to control. To
      differentiate between possible central and peripheral components of the
      hyperactivity of wide dynamic range cells we performed in situ dorsal rhizotomy
      during the recording. Cutting the dorsal roots (L2-5) evoked a significantly
      larger and more prolonged discharge in wide dynamic range cells in both UV
      treated groups in comparison to control. Spontaneous activity in spinal wide
      dynamic range neurons was reduced after rhizotomy in each group. However, the
      decrease was only significant at days 1-3 (P < 0.05) but not at days 5
      7.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278051
TI  - Ethical and moral considerations in the design of experiments.

PMID- 8278052
TI  - The significance of alternative methods for the reduction of animal experiments
      in the neurosciences.

PMID- 8278053
TI  - The role of education in understanding the use of animals in research.

PMID- 8278054
TI  - Antivivisectionist attacks on neuroscientists: fighting back.

PMID- 8278055
TI  - Potentiation of nerve growth factor-induced alterations in cholinergic fibre
      length and presynaptic terminal size in cortex of lesioned rats by the
      monosialoganglioside GM1.
AB  - The effect of monosialoganglioside GM1 and/or nerve growth factor treatment on
      the cholinergic innervation of the rat cortex was studied using both light- and
      electron-microscopic techniques assisted by image analysis. Adult male Wistar
      rats were unilaterally decorticated and received continuous infusions, via
      minipump, of vehicle, GM1 (1.5 mg/day) and/or nerve growth factor (12
      micrograms/day) into the cerebroventricular space. Treatments were initiated
      immediately post-lesion and ended after seven days. Thirty days post-lesion (i.e.
      23 days after the end of drug administration) brains were processed for choline
      acetyltransferase immunocytochemistry for either light- or electron-microscopic
      analysis. At this time-point choline acetyltransferase-immunoreactive neurons in
      the ipsilateral nucleus basalis magnocellularis were significantly reduced in
      size especially in the mid portion of this nucleus, in lesion vehicle-treated
      rats. Moreover, decreases in choline acetyltransferase immunoreactive fibre
      length (ranging from 31 to 50%) and varicosity number (ranging from 26 to 39%)
      occurred in all cortical layers within a portion of the remaining cortex of these
      animals. Monosialoganglioside GM1 or nerve growth factor treatment equally
      attenuated deficits in nucleus basalis magnocellularis cell size and cortical
      choline acetyltransferase immunoreactive fibre length. However, nerve growth
      factor, but not monosialoganglioside GM1 treatment also increased choline
      acetyltransferase-immunoreactive varicosity number above control levels. In
      lesioned rats which received both nerve growth factor and the
      monosialoganglioside GM1, the mean cross-sectional area of nucleus basalis
      magnocellularis cholinergic neurons did not differ significantly from control
      values. By contrast, cortical choline acetyltransferase-immunoreactive fibre
      length and varicosity number were significantly increased above control values
      and that induced by nerve growth factor treatment alone. Quantitative electron
      microscopic analysis showed that cholinergic boutons in cortical layer V were
      considerably shrunken in lesioned vehicle-treated rats and that GM1 treatment
      failed to significantly attenuate this deficit. However, exogenous nerve growth
      factor provoked a significant increase (35% above control values) in cortical
      cholinergic presynaptic terminal size which was even further augmented by
      concurrent GM1 treatment (69% above control values). This trophic factor-induced
      increase in bouton size was confirmed using serial electron microscopy and
      computer-assisted three-dimensional reconstruction of the cholinergic
      varicosities. The number of synaptic contacts in cortical layer V was also found
      to be significantly reduced (45% of control values) in lesioned vehicle-treated
      rats but was maintained at control levels by exogenous GM1 treatment. In
      addition, a significant increase (95% above control levels) in the number of
      choline acetyltransferase-immunoreactive boutons with synaptic differentiations
      was noted in lesioned nerve growth factor-treated rats.(ABSTRACT TRUNCATED AT 400
      WORDS)

PMID- 8278056
TI  - Science, magic and political action: a response to the antivivisection movement.

PMID- 8278057
TI  - Neuroscience and the media: the need for communication.

PMID- 8278058
TI  - The KROX-20 transcription factor in the rat central and peripheral nervous
      systems: novel expression pattern of an immediate early gene-encoded protein.
AB  - The KROX-20 protein (also termed EGR-2) is encoded by an immediate early gene
      cloned by cross-hybridization to the Drosophila melanogaster Kruppel gene. It
      belongs to a class of transcription factors with zinc finger motifs and binding
      activity to a transcriptional regulatory DNA element termed the early growth
      response consensus sequence. In the present study the temporospatial expression
      of KROX-20 was investigated in the central and peripheral nervous systems of
      normal rats and after various stimuli known to induce immediate early genes,
      including epileptic seizures, axotomy, pharmacological treatment with glutamate
      and alpha-adrenergic receptor antagonists, and peripheral noxious stimulation.
      Immunocytochemistry was performed with a specific polyclonal antiserum generated
      against a fusion protein containing KROX-20 sequences. In the central nervous
      system, KROX-20 protein demonstrated distinct constitutive nuclear expression in
      specific neuronal subpopulations of the cortex, septum, amygdala, olfactory bulb
      and hypothalamus. In addition, distinct cytoplasmic immunoreactivity was present
      in spinal and medullary motoneurons, dorsal root ganglion neurons and a few
      neuronal cell populations of midbrain and forebrain. In the CNS, KROX-20 was only
      induced by bicuculline-induced epileptic seizures. Topographically, the postictal
      increase of KROX-20 levels was restricted to areas with constitutive expression,
      such as cerebral cortex, fornix and amygdala. Induction of KROX-20 peaked at 4-8
      h after onset of seizure activity. No increase in immunoreactivity was observed
      in the hippocampus, the brain region most severely affected by bicuculline
      induced seizures. Transection of central and peripheral nerve fibers did not
      result in KROX-20 induction in axotomized neurons. However, KROX-20 was induced
      in Schwann-like cells after transection of the sciatic nerve. In contrast to KROX
      20, KROX-24, a related transcription factor of the zinc finger family, was
      markedly induced in hippocampal and spinal neurons following seizures and
      peripheral noxious stimulation, respectively, as well as in CNS neurons following
      axotomy. Our data indicate that KROX-20 represents an immediately early gene
      product with basal expression in selected neuronal populations of the nervous
      system and a restricted inducibility after intentional stimuli.

PMID- 8278059
TI  - Expression of immediate early gene proteins following axotomy and inhibition of
      axonal transport in the rat central nervous system.
AB  - The expression of the immediate early gene-encoded proteins c-Jun, Jun B, Jun D,
      c-Fos, Fos B and Krox-24 in central neurons following transection of, or
      inhibition of, axonal transport in their axons was investigated in the rat using
      immunocytochemistry. Transection of the medial forebrain bundle, which produces
      an essentially complete axotomy of neurons in the ipsilateral mammillary nucleus,
      substantia nigra pars compacta, ventral tegmental area and parafascicularis,
      induced the expression of c-Jun, Jun D and, to a lesser extent, Krox-24, in these
      nuclei. Microinjection of colchicine into the medial forebrain bundle to
      chemically inhibit axonal transport similarly induced the expression of these
      proteins in these areas. The expression of the proteins was first evident 24 h
      after transection, reached a maximum at 48 h and was still present after 10 days.
      However, after 30 days the proteins were absent from the substantia nigra,
      ventral tegmentum and parafascicularis, and were still present only in the
      mammillary nuclei. The other immediate early genes, Jun B, c-Fos and Fos B, were
      never expressed above the basal levels seen in untreated rats. Transection of the
      corpus callosum and the hippocampal commissure, which produces only a partial
      axotomy of neurons in the cerebral cortex and hippocampus, respectively, did not
      induce the expression of any of the genes in these neurons. Microinjection of
      colchicine or vinblastine to produce a localized inhibition of axonal transport
      in the cerebral cortex, hippocampus, thalamus and cerebellum also induced the
      expression of c-Jun, Jun D and, again to a lesser extent, Krox-24, in neurons
      surrounding the injection site. In contrast to this selective expression,
      administration of the neuronal excitant metrazole induced the expression of all
      six immediate early gene proteins in central nervous system neurons. These
      results demonstrate that transection of, or inhibition of, transport in the axons
      of central neurons induces a particular pattern of expression of
      transcriptionally operating immediate early genes that may be related to the
      regenerative competency of the neurons.

PMID- 8278061
TI  - [Technologic progress: the morphometer].

PMID- 8278060
TI  - Promotion of granule cell survival by high K+ or excitatory amino acid treatment
      and Ca2+/calmodulin-dependent protein kinase activity.
AB  - Cerebellar granule cells in culture develop survival requirements which can be
      met either by chronic membrane depolarization (25 mM K+) or by stimulation of
      ionotropic excitatory amino acid receptors. We observed previously that this
      trophic effect is mediated via Ca2+ influx, either through dihydropyridine
      sensitive, voltage-dependent calcium channels (activated directly by high K+ or
      indirectly by kainate) or through N-methyl-D-aspartate receptor-linked ion
      channels. Steps after Ca2+ entry in the transduction cascade mediating the
      survival-supporting effect of high K+ and excitatory amino acids have now been
      examined. Using protein kinase inhibitors (H-7, polymixin B and gangliosides),
      and modulating protein kinase C activity by treatment with the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate, we obtained evidence against the involvement of
      protein kinase C and cyclic nucleotide-dependent protein kinases in the
      transduction cascade. On the other hand, calmidazolium (employed as a calmodulin
      inhibitor) counteracted the trophic effect of elevated K+ with high potency (IC50
      0.3 microM), which exceeded by approximately 10-fold the potency for the blockade
      by the drug of voltage-sensitive calcium channels. The potency of calmidazolium
      in interfering with the N-methyl-D-aspartate rescue of cells was also much higher
      in comparison with the inhibition of 45Ca2+ influx through N-methyl-D-aspartate
      receptor-linked channels. Our results indicated that after calmodulin the next
      step in the trophic effects involves Ca2+/calmodulin-dependent protein kinase II
      activity. KN-62, a fairly specific antagonist of this enzyme, compromised
      elevated K+ or excitatory amino acid-supported cell survival with high potency
      (IC50 2.5 microM). In the relevant concentration range, KN-62 had little or no
      effect on Ca2+ entry through either voltage- or N-methyl-D-aspartate receptor
      gated channels. Combining information on the toxic action of glutamate in
      "mature" granule cells with the trophic effect of either excitatory amino acids
      or high K+ treatment on "young" cells, we conclude that after the initial steps
      involving calcium in both cases the respective transduction pathways diverge. The
      toxic action of glutamate seems to be mediated through protein kinase C [Favaron
      et al. (1990) Proc. natn. Acad. Sci. U.S.A. 87, 1983-1987 whereas a
      Ca2+/calmodulin-dependent protein kinase, which can be inhibited by KN-62 (but is
      resistant to gangliosides and to inhibitors whose potency is higher for protein
      kinase C than for Ca2+ calmodulin-dependent protein kinases, such as H-7 and
      polymixin B), is involved critically in the trophic effect.

PMID- 8278062
TI  - [Cerebral protection].
AB  - Cerebral protection means prevention of cerebral neuronal damage. Severe brain
      damage extinguishes the very "human" functions such as speech, consciousness,
      intellectual capacity, and emotional integrity. Many pathologic conditions may
      inflict injuries to the brain, therefore the protection and salvage of cerebral
      neuronal function must be the top priorities in the care of critically ill
      patients. Brain tissue has unusually high energy requirements, its stores of
      energy metabolites are small and, as a result, the brain is totally dependent on
      a continuous supply of substrates and oxygen, via the circulation. In complete
      global ischemia (cardiac arrest) reperfusion is characterized by an immediate
      reactive hyperemia followed within 20-30 min by a delayed hypoperfusion state. It
      has been postulated that the latter contributes to the ultimate neurologic
      outcome. In focal ischemia (stroke) the primary focus of necrosis is encircled by
      an area (ischemic penumbra) that is underperfused and contains neurotoxic
      substances such as free radicals, prostaglandins, calcium, and excitatory
      neurotransmitters. The variety of therapeutic effort that have addressed the
      question of protecting the brain reflects their limited success. 1) Barbiturates.
      After an initial enthusiastic endorsement by many clinicians and years of
      vigorous controversy, it can now be unequivocally stated that there is no place
      for barbiturate therapy following resuscitation from cardiac arrest. One presumed
      explanation for this negative statement is that cerebral metabolic suppression by
      barbiturates (and other anesthetics) is impossible in the absence of an active
      EEG. Conversely, in the event of incomplete ischemia EEG activity in usually
      present (albeit altered) and metabolic suppression and hence possibly protection
      can be induced with barbiturates. Indeed, most of the animal studies led to a
      number of recommendations for barbiturate therapy in man for incomplete ischemia.
      2) Isoflurane. From a cerebral metabolic standpoint, exposure to isoflurane at
      concentration of 2 MAC is credited with providing the same potential for
      protection as high dose barbiturate (isoelectric EEG). A possible major
      difference between barbiturates and isoflurane is the modest cerebral
      vasodilation induced by the latter while barbiturates are associated with
      decreased CBF. This suggests that in focal ischemia isoflurane may elicit an
      intracerebral steal. 3) Calcium entry blockers. Some calcium entry blockers with
      the distinctive feature of acting preferably on cerebral as opposed to systemic
      vascular smooth muscles may exert beneficial effects during or after brain
      ischemia. Two such drugs which have shown promise are nimodipine and lidoflazine.
      In animal and human studies nimodipine has been reported to improve the
      neurologic outcome of both the cerebral vasospasm and the postischemic
      hypoperfusion state.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8278063
TI  - [Induction of bacterial translocation in rats with minimal doses of endotoxin].
AB  - OBJECTIVE: To determine whether a non lethal dose of intramuscular endotoxin in
      rats causes a physical disruption of the mucosal barrier and promotes the
      translocation of bacteria from gut to visceral organs. DESIGN: Prospective
      randomized trial. SETTING: Experimental laboratory university medical center.
      EXPERIMENTS: 60 male wistar rats, weighing 250 g. INTERVENTIONS: six hours and
      twenty-four hours after endotoxin (8 mg/kg) or saline (control group) given
      intramuscularly, rats were sacrificed and mesenteric lymph nodes, spleen and some
      segments of the ileum were removed. Lymph nodes and spleen were cultured for
      translocating bacteria while ileum segments were observed by light microscopy.
      RESULTS: Incidence of bacterial translocation increases from 6 hours (40% p <
      0.05) to 24 hours (60%, p < 0.01) after endotoxin administration. Histologic
      evaluation of the ileum demonstrated that a mucosal injury occurred only at the
      24 an hour and that it was characterized by an evident pronounced interstitial
      edema with focal breaks in the basal membranes of villous and glands.
      CONCLUSIONS: It appears that microorganisms and microbial products contained in
      the gut can cross the mucosal barrier and spread into other visceral organs also
      after a low dose of intramuscular endotoxin.

PMID- 8278064
TI  - [Conventional radiology and computerized axial tomography in the diagnosis of
      pneumothorax in intensive therapy. Retrospective study of 2 years of activity].
AB  - The role played by chest radiograph and CT scan in diagnosis of pneumothorax is
      analyzed in a retrospective study based on two years of activity in Intensive
      Care Unit. The sensibility of traditional chest radiography was 75% while the
      sensibility of CT scan resulted higher (87.5%). In the authors opinion, when
      pneumothorax is suspected, particularly in patients with polytrauma, CT scan of
      the chest is mandatory unless patient's conditions or logistic difficulties
      related with transport of the patient contraindicate it.

PMID- 8278065
TI  - [Concentrations of propofol in maternal and fetal blood during anesthesia for
      cesarean section].
AB  - The authors studied, until the delivery, the pharmacokinetics of propofol during
      cesarean section. Ten patients were studied. Anaesthesia was induced and
      maintained with propofol (2 mg/kg in 15 seconds; 3 mg/kg/h until the end of the
      operation). All the patients have been intubated after the administration of
      atracurium 0.4 mg/kg and artificially ventilated with O2/N2O (FiO2 0.4). A series
      of maternal blood samples was obtained. Umbilical artery and venous blood samples
      have been obtained at delivery. Propofol levels in whole blood samples have been
      measured by a HPLC method (High pressure liquid chromatography). The results
      were: at delivery the mean ratio of the drug concentration in the umbilical vein
      to that in maternal vein was 0.53 +/- 0.16 micrograms/ml; the mean concentration
      in the umbilical vein was 0.96 +/- 0.31 micrograms/ml. The anaesthesiological
      protocol was clinically satisfactory and had no adverse effects on mother and
      foetus.

PMID- 8278066
TI  - [Propofol-midazolam in continuous infusion for sedation in intensive care].
AB  - Two groups of 11 ICU respiratory patients ventilated with PSV have been sedated
      with propofol (group I) or with midazolam (group II). After the endovenous
      administration of the induction dose (propofol 1.5 mg/kg; midazolam 0.15 mg/kg)
      sedation was obtained with continuous infusion of the drugs (propofol 2 mg/kg/h;
      midazolam 0.24 mg/kg/h). In this setting the Authors evaluated the level of
      sedation (Ramsey scale) and the side effect of the two drugs. At induction
      midazolam caused a reduction of tidal volume for some minutes and a greatest
      sedation in comparison with propofol, while propofol caused reduction of MAP (p <
      0.01) and transitory apnoea. Even if during the infusion of propofol the level of
      sedation decreased with time (p < 0.05; y = -0.0357 x + 3.07) it was more stable
      in comparison with that registered during continuous infusion of midazolam (p <
      0.01; y = -0.2018 x + 5.19.

PMID- 8278067
TI  - [Analgesic effect of sodium meclofenamate on several painful symptoms].
AB  - Three groups of 20 patients, who suffered of acute pain (dental or low back or
      menorrhalgia) have been randomized and treated, obtained their informed consent,
      with meclofenamic acid 100 mg or ketoprofene 50 mg by oral route. The study has
      been completed double blind to assess the powerful antalgic effect between the
      two drugs, the results underline that the two NSAID have a very good effect on
      pain of various nature. The patients have obtained a complete relief not always,
      but it appears very quickly also by oral route. Statistical analysis has revealed
      that meclofenamic acid effects are swifter than for ketoprofene, but the latter
      seems to have a longer action.

PMID- 8278068
TI  - [Conversion between APACHE II and SAPS. Italian Multicentric Group for Research
      on Intensive Therapy (FIRTI II)].

PMID- 8278069
TI  - [ARDS in a severe case of primary pulmonary infection caused by Legionella
      pneumophila].
AB  - The authors report a case of ARDS following pneumonia caused by Legionella
      pneumophila, in a thirty year old young man. Mechanical ventilation was
      maintained for twenty days. The gravity of ARDS and pneumonia, perhaps was caused
      because infective agent and the efficacious antibiotic were identified too late:
      twelve days after the comparison of symptoms. In fact, early laboratory diagnosis
      of Legionella pneumonia, is currently very difficult. A primitive extranocosomial
      pneumonia with rapid development to ARDS, in a good health young man, is an
      uncommon event. The exclusion of particular causes of ARDS, such as narcotic over
      dose, AIDS, lung cancer, lymphatic carcinomatosis, and the clinical suspicion of
      Legionella pneumonia presence, can be useful: waiting for the right diagnosis
      from the laboratory, it will be possible to begin antibiotic therapy with
      Erythromycin (often used for slight respiratory infections), and to prevent the
      evolution of illness.

PMID- 8278070
TI  - [Report of a case of spontaneous thrombolysis].
AB  - Spontaneous thrombolysis is a quite rare event. It's not predictable through a
      clinical examination of the patient, but there are some markers that are supposed
      to be diagnostic because of the high percentage of their occurrence in
      coincidence with spontaneous thrombolysis. The goal of the authors is to describe
      a case of spontaneous thrombolysis in a middle age men (62 years). The diagnosis
      was done by the use of the most typical markers.

PMID- 8278071
TI  - [Morphine sulfate per os combined with octreotide in continuous peridural therapy
      in oncologic pain. Description of a clinical case].
AB  - The authors emphasize the analgesic synergy of the association of morphina
      sulphate per os and octreotide in continuous epidural therapy in a patient
      affected by a late prostatic cancer with diffuse skeletal metastases. They,
      moreover, support cenesthesia regulating and, perhaps, antiproliferative activity
      of octreotide. A few patients treated with octreotide in continuous epidural
      therapy showed neurological diseases of behaviour.

PMID- 8278072
TI  - [Unilateral pulmonary edema caused by heart failure. Report of 2 clinical cases].
AB  - The authors present two case reports of cardiogenic unilateral pulmonary edema.
      The information provided by hemodynamic monitoring have not been essential for
      diagnosis which was bases on clinical, radiological and echocardiographic
      findings and confirmed by the clinical response to a specific treatment. The
      authors briefly review the mechanisms which may cause the atypical distribution
      of the cardiogenic pulmonary edema.

PMID- 8278073
TI  - [A device to prevent the twisting of totally implantable spinal catheters].

PMID- 8278074
TI  - [Aspiration syndrome in cesarean section].

PMID- 8278075
TI  - [Severity (SAPS), intensity of treatment (TISS), and mortality in patients with
      COPD].

PMID- 8278076
TI  - [Directions of future research on GnGH analogs in the treatment of endometriosis
      and uterine fibromyoma].
AB  - A variety of new data on the biology, pathophysiology and metabolic changes
      occurring in leiomyomas and in the ectopic endometrium have opened new avenues
      for research in a neglected area, that of benign proliferations of the female
      reproductive tract. In addition, the availability of potent inhibitors of ovarian
      function which, like the super-agonist analogues of GnRH, have no hormonal
      activity (oestrogenic, progestogenic or androgenic) has allowed for the first
      time to evaluate the effect of oestrogen deprivation on endometriosis and uterine
      fibrosis. The results, although impressive, are only temporary: in both cases
      hypoestrogenism produces an important relief of symptoms, but--once treatment is
      discontinued--both conditions usually continue to evolve. For this reason, much
      remains to be done to optimize Gn-RH analogue utilization. In the case of
      endometriosis, there seem to be three main areas for future research: pain,
      infertility and the possibility of modifying its natural history. In addition,
      the role of combined, medico-surgical therapy remains to be established,
      especially in the case of severe disease. In the treatment of fibrosis, analogues
      can be utilized as pre-treatment before conservative or demolitive surgery, or as
      an alternative to hysterectomy. The role of analogues as a pre-surgical adjuvant
      has probably been overemphasized and it is time to carry out well controlled
      studies to narrow down indications. At present they include: severe anemia caused
      by chronic heavy uterine bleeding, and the need to minimize intraoperative blood
      loss. Much remains to be done before analogues can become a real alternative to
      surgery. To date no single sequential therapeutic regimen has been identified
      which is capable of prolonging the beneficial effects of agonists without their
      well known negative consequences. Temporary results can be obtained interrupting
      analogue therapy and substituting it with the administration of a progestogen.
      Finally, analogue administration can be prolonged by associating an oestrogen
      progestogen sequential combination as in HRT. In all of these instances, what are
      urgently needed are well controlled randomized clinical trials.

PMID- 8278077
TI  - [Infectious complications in oncologic-gynecologic surgery: clinical and economic
      evaluation].
AB  - In the Department of Obstetric and Gynecology, Faculty of Medicine-Varese,
      between March 1991 and June 1992, 74 consecutive patients undergoing elective
      oncologic surgery were evaluated in order to rationalize the use of antibiotics
      to decrease the costs of infectious complications. We divided the patients into
      two groups: a high infection risk group (in which every patient was submitted to
      antibiotic prophylaxis) and a low infection risk group (in which we didn't use
      any antibiotic prophylaxis). Our findings indicate that selection criteria for
      HIR patients are probably correct and in this group AP is necessary. In the LIR
      group, 45.5% of patients was not submitted to any antibiotic therapy. It's
      necessary to test the real efficacy of an AP in LIR patients in whom we had not a
      important incidence of infectious complications. In the LIR group AP should not
      exceed Lit. 23,251 per patient to be cost-effective.

PMID- 8278078
TI  - [Ultrasonic evaluation of the uterus during puerperium].
AB  - The aim of this study was to evaluate morphological and volumetric changes in the
      uterus during the first eight days postpartum in a sample of 229 patients using
      ultrasonography. Both pregnancies and postpartum were physiological in all the
      women examined. Fifty patients underwent cesarean section. A sectorial 3.5 MHz
      probe was used to measure the longitudinal, antero-posterior and latero-lateral
      diameter of the uterus and its volume. Involution was gradual both in relation to
      the diameters and uterine volume up until day 8 and was most evident during days
      1-4. Longitudinal and antero-posterior diameter reduced more quickly in relation
      to the latero-lateral diameter. Uterine volume, calculated by considering the
      uterus as an ellipsoid, diminished 42% from 730 cc to 421 cc. No differences were
      observed between uterine diameters in primiparas and those in pluriparas, nor
      between patients undergoing cesarean section and those after normal childbirth.
      However, there was a clear difference between those patients who breastfed
      immediately after birth and those who resorted to artificial methods; uterine
      volume diminished more rapidly in the former, especially between days 1-4,
      confirming that early breastfeeding plays an important role in uterine involution
      in the very early days of postpartum. The physiological characteristics of the
      postpartum uterus were useful in formulating a medical or surgical treatment
      strategy in the few cases of postpartum metrorrhagia observed during the study.

PMID- 8278079
TI  - [Vaginitis and vaginosis. Comparison of two periods].
AB  - Vaginitis is the most frequent gynecological disease. It is characterized by
      objective and subjective signs of inflammation and differs from bacterial
      vaginosis (BV) which is an abnormal condition of the vaginal ecosystem caused by
      the excessive growth of aerobic and anaerobic flora normally present in the
      vagina with an increased risk of pelvic inflammatory disease (PID). The authors
      report the results of a study carried out at the Centre for Gynecological
      Infections at the Clinic of Obstetrics and Gynecology of the University of Parma.
      828 patients were enrolled in the study during the period 1985-86 and 1559
      patients during the two-year period 1991-92. The aim of the study was to evaluate
      variations in epidemiological data for vaginitis and bacterial vaginosis in the
      two periods examined. No significant changes were observed (p > 0.05) with regard
      to the prevalence of Ca, Tv and BV forms. On the other hand, there was a
      significant reduction (p < 0.001) in the forms sustained by other microorganisms
      (above all, streptococcus and enterobacteria) between the first and second
      periods with a parallel increase in the number of negative cases. The analysis of
      the age distribution of vaginitis and BV showed a reduction of other
      microorganisms and an increase in negative vaginal swabs in adults (> 20 years
      old).

PMID- 8278080
TI  - [Postmenopausal gynecologic pathology: 5-years activity at an ambulatory
      ultrasonography clinic].
AB  - The authors examine the role of ultrasonography in the diagnosis of gynecological
      post-menopausal pathologies and report the activities of the ultrasound out
      patient clinic over the past 5 years. Due to the prolonged life expectation of
      women and consequently the growing request for gynecological examinations,
      increased importance has been given to the pathologies typical of this age
      bracket Gynecological exploration if often difficult in elderly patients leading
      to an increased request for ultrasonography in addition to clinical examination.
      Transvaginal ultrasonography allows the pelvic structures and endometrial echo
      pattern to be examined with greater accuracy. During the period from 1986 to 1991
      a total of 405 postmenopausal women were examined using ultrasonography out of a
      total of 3505 gynecological scans. Scans were performed using a 3.5 MHz
      suprapubic or endovaginal probe. The most frequent pathology was malignant
      endometrial carcinoma and the most frequent clinical symptoms was metrorrhagia.
      In line with findings reported in the literature, the authors underline the vital
      importance of carefully controlling all perimenopausal women attending an
      ultrasound out-patient clinic who present risk factors or metrorrhagia using
      integrated transabdominal and endovaginal diagnosis. The use of the endovaginal
      probe allows images to be obtained which are otherwise not visible using the
      transabdominal approach, thus permitting suspect echographic patterns to be
      identified. Moreover, endometrial evaluation represents an important stage of the
      examination. It is obvious that the endovaginal approach represents a useful
      diagnostic technique for screening purposes, especially in high-risk groups for
      endometrial pathology and ovarian cancer.

PMID- 8278082
TI  - [Studying the therapeutic effectiveness of iron acetyl transferrin in sideropenic
      hypochromic anemia in females].
AB  - The Authors evaluated the effects and tolerability of iron acetyl transferrin in
      fifty women affected by anemia for want of iron. The patients were given oral
      iron treatment (80 mg/die) for 30 days; commonest haematologic parameters were
      examined (RBC, HTC, MCV, MCH, serum iron, ferritin, transferrin) before and after
      treatment. The results show that iron acetyl transferrin has an excellent
      therapeutic effect and a good tolerability.

PMID- 8278081
TI  - [Treatment of HPV-positive CIN1 and CIN2 with intralesion administration of human
      interferon from fibroblasts associated with DTC (diathermal coagulation) of the
      cervical portio].
AB  - The aim of this study was to draw attention to the efficacy of the therapeutic
      association of intralesional beta-IFN-DTC of the portio in HPV-positive CIN1 and
      CIN2 in 25 women aged between 21 and 41 years of age. Control tests after the
      completion of treatment showed complete recovery from CIN and the disappearance
      of the virus. Side effects were minimal and in no instance did they affect
      patients' normal activities or lead to an interruption of therapy. No cases of
      recidivation or relapse were reported 12 months after the completion of therapy.

PMID- 8278083
TI  - [Giant ovarian dermoid cyst in prepubertal age. Report of a case].
AB  - We report a case of a very large (size cm 33 x 41) dermoid cyst in the right
      ovary in a 11 year old child, causing a complete atrophy of the remaining right
      ovarian parenchyma and ipsilateral salpinx. Sonography and CT allowed us to
      diagnose this disease and also showed an associated ureterohydronephrosis. The
      patient underwent a surgical operation during which a right ovarosalpingectomy
      was performed. A rapid regression of the ureterohydronephrosis was observed and
      the patient was discharged from the hospital six days after operation.

PMID- 8278084
TI  - [Kerion of the vulva. Report of a case and review of the literature].
AB  - We report a case of a 43 year old woman who developed an extensive vulvar kerion
      caused by Trichophyton menthagrophytes that was initially mistaken for a
      bacterial infection. The peculiarity of this case lies in the fact that the
      kerion is rarely located in the vulva and it has not yet been described in the
      literature. On the contrary, cases have been found in the scalp, beard, eye-brow,
      etc. We discuss the etiopathogenetic aspects, criteria for differential diagnosis
      and therapy management of this rare clinical picture.

PMID- 8278085
TI  - [A rare complication of obstetric pathology: uretero-uterine fistula].
AB  - Accidental iatrogenic injuries of ureters and bladder in patients with abdominal
      and pelvic pathology are described as a possible lesion of a surgical or
      gynaecologic treatment. The ureteral lesion is less frequent in obstetric
      surgery, but the young age of the patients and the gravity of the consequences,
      impose a very serious problem for a early diagnosis with a conservative surgical
      treatment. On the contrary, this important injury, bears an important surgical
      management with possible functional damage of the reno-urinary tract. The Authors
      report the experience about the observation and treatment of a case of a young
      woman, 29 years old, who had a uretero-uterine fistula, after a cesarean section
      for the first pregnancy.

PMID- 8278086
TI  - [George Nicholas Papanicolaou].
AB  - G. N. Papanicolaou was born on May the 13, 1883 in the city of Kymi on the Greek
      island of Euboea. He received his MD degree from the University of Athens in 1904
      and a PhD from the University of Munich in 1910. After service as a medical
      officer in the Balkan War of 1912-1913, he came to New York with Mary (for over
      50 years Dr Pap's life companion). George's violin playing at restaurants and
      coffee-shops supplied them with a few extra cents. Papanicolaou was appointed
      assistant in the Pathology Laboratory at the New York Hospital. In 1928 he
      presented his work "New Cancer Diagnosis" to the third race betterment conference
      (Battle Creek, Michigan). But the work was met with scepticism. The now famous
      monograph "The Diagnostic Value of Vaginal Smears in Carcinoma of the Uterus" was
      published in 1941 in the Am J Obst Gyn. During this time, he developed his method
      of preservation of these cells by wet fixation and precise staining. Papanicolaou
      persisted with his ideas, and finally cytologic examination of the cervix was
      accepted. The power of Papanicolaou screening for uterine cancer was remarkable.
      The first National Cytology Congress, held in 1948, hailed this new diagnostic
      tool for carcinoma of the cervix as unique because it could detect cancer before
      it was visible. He described the importance of a distinct cellular pattern
      corresponding to cervical intraepithelial neoplastic lesions. The value of this
      pattern, expressing evolutionary steps in the development of cancer at individual
      cell levels, was not appreciated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278087
TI  - Terfenadine, astemizole and loratadine: second generation antihistamines.

PMID- 8278088
TI  - Acupressure wristbands for the nausea of pregnancy.

PMID- 8278089
TI  - Therapeutic touch for the elderly.

PMID- 8278090
TI  - Progestogens: a look at the "other" hormone.
AB  - Health care providers need a general understanding of progestogens to use them
      safely and effectively in practice. These hormone formulations are used
      extensively in combination oral contraceptives and in hormonal replacement
      therapy with estrogen or alone. Although considered relatively safe for most
      women, it is important to look closely at the actions of the various progestogens
      and associated impacts. Major concerns regarding the use of these preparations
      center on potential untoward lipoprotein changes, carbohydrate metabolism
      alterations, and breast cancer. Other concerns relate to coagulation effects,
      prostacyclin changes, sex hormone-binding globulin capacity, psychological
      disturbances, blood pressure alterations, breakthrough bleeding, headaches, and
      other side effects. Over the years progestogen preparations have evolved into
      safer formulations with fewer apparent risks.

PMID- 8278091
TI  - Assessment and management of persons coinfected with tuberculosis and human
      immunodeficiency virus.
AB  - After eight decades of decline, cases of tuberculosis (TB) have increased
      substantially since 1985. This increase is attributed largely to a reactivation
      of disease in persons who are coinfected with TB and human immunodeficiency virus
      (HIV). Multiple-drug resistant tuberculosis (MDR-TB) has a high mortality rate
      (70 to 90%), mostly occurring in individuals with HIV. Death often results within
      4 to 16 weeks of diagnosis. The pathogenesis, screening, chemoprophylaxis,
      diagnosis, and treatment of persons coinfected TB and HIV is reviewed. Attention
      is given to infection control and occupational exposure. A chart of commonly
      prescribed antituberculosis medications is listed, including recommended adult
      dosages, side effects, and drug interactions. Clinicians must incorporate
      meticulous TB screening and treatment for all patients coinfected with HIV and
      TB.

PMID- 8278092
TI  - Examining the common stressors and coping methods of rural adolescents.
AB  - The major objective of this study was to explore and examine common stressors and
      coping strategies of rural adolescents. Coping was defined as a cognitive and
      transactional process between a person and the person's environment. A survey of
      222 normal adolescents attending a rural southwestern Pennsylvania high school
      reported experiencing stressful events related to school, family, friendship,
      health, and transportation. The coping strategy reported as being the most
      commonly used was optimistic. However, the coping strategy reported to be most
      effective in dealing with stressful events was supportant. The results of this
      study contribute to the limited information on adolescent coping in rural areas.
      This study should help health care providers further their understanding of this
      vulnerable population. Clinicians can enhance the effective coping and overall
      health of the rural adolescent by screening for and discussing coping strategies.

PMID- 8278093
TI  - Latex allergy: recognition and management of a modern problem.
AB  - Within the past decade, anaphylaxis from latex products has been a recognized
      clinical crisis. Immediately after contact with latex, the patient can experience
      urticaria, nasorhinitis, conjunctivitis, asthma, hypotension, and shock. Health
      care workers, children with spina bifida, patients with a history of urogenital
      procedures, and employees of rubber manufacturing plants have the highest
      incidence. The most common denominators include frequent contact with latex and a
      history of allergies, although cases without these components have been reported.
      The increased incidence is linked to the increase of glove and condom use in
      preventing the spread of the HIV virus. Sensitization to the natural rubber
      protein is the allergen, although the specific protein has not been isolated. A
      thorough medical and surgical history and a history of previous allergies and
      allergic events should be collected on all patients with complaints of any latex
      contact symptoms. Latex-sensitive patients should wear a Medic Alert bracelet and
      carry an epinephrine autoinjector kit. Health care providers must be alert for
      the possible occurrence of latex sensitivities in their patients.

PMID- 8278094
TI  - How reliable is your patient's pain assessment?

PMID- 8278095
TI  - 25 tips on hand washing. See if you know them all.

PMID- 8278096
TI  - Checking your patient's complement assay.

PMID- 8278097
TI  - Managing pain with transdermal fentanyl.

PMID- 8278098
TI  - Urinary diversion with an Indiana pouch.

PMID- 8278099
TI  - Detecting torsades de pointes.

PMID- 8278100
TI  - Standing guard against silent ischemia & infarction.

PMID- 8278101
TI  - God's mechanic.

PMID- 8278102
TI  - Examining women's risk for heart disease.

PMID- 8278103
TI  - Steering clear of trouble: litigation lessons.

PMID- 8278104
TI  - Identifying & managing dysphagia.

PMID- 8278105
TI  - How to use a disposable end-tidal CO2 detector.

PMID- 8278106
TI  - Letting go of a loved one.

PMID- 8278107
TI  - Streamlined charting for patient education.

PMID- 8278108
TI  - A bearable solution: responding creatively to dementia.

PMID- 8278109
TI  - How to inject a subcutaneous abdominal implant.

PMID- 8278110
TI  - Working healthier.

PMID- 8278111
TI  - Why become certified?

PMID- 8278112
TI  - A suitable profession.

PMID- 8278113
TI  - Initiatives in dental education.

PMID- 8278114
TI  - A new approach to the training and education of oral health personnel.
AB  - An innovative curriculum has been designed for the Fiji School of Medicine to
      enable dental personnel to proceed through a sequence of educational modules on a
      career path leading from a dental assistant through other auxiliary grades to a
      dentist with a BDS degree. The courses for each grade are formulated to be
      relevant to the pattern of oral diseases in Fiji and the Pacific Islands; be
      designed in accordance with specified job-descriptions; have a strong community
      orientation, with emphasis on prevention and the promotion of oral health; permit
      exit and re-entry at each level; incorporate, where appropriate, the principle of
      problem-based learning; and incorporate procedures to ensure early establishment
      of clinical skills. Details of the first year and an outline of the structure of
      the course for the subsequent years are presented.

PMID- 8278115
TI  - Familial gingival fibromatosis: a report of two patients.
AB  - This report describes two patients with familial gingival fibromatosis. Treatment
      for both patients involved gingivectomies to provide acceptable gingival function
      and appearance. The first patient has been monitored for only a short period, the
      second patient for 11 years. Neither patient has shown any recurrence of the
      condition.

PMID- 8278116
TI  - Dohnavur Fellowship--an experience of dentistry in south India.

PMID- 8278117
TI  - Dankto doctar: the tooth doctor. Dentistry in Nepal.

PMID- 8278118
TI  - In my opinion: the specialist in community dentistry or dental public health.
AB  - The traditional role of the Principal Dental Officer will disappear under the
      1993 health-service reforms. The specialist in Community Dentistry will be
      required to define need, suggest appropriate solutions from available resources
      to the need, and to monitor outcome. These recommendations should be based upon
      local knowledge. In the immediate short term, the design, implementation, and
      evaluation of pilot projects will be an important role. Most of the functions of
      the specialist will be required within the Regional Health Authorities, but some
      Crown Health Enterprises will also require these skills.

PMID- 8278119
TI  - Root caries: some clinical aspects.
AB  - This paper has discussed some aspects of root surface caries which are of special
      relevance to the clinician. Epidemiological studies have suggested that root
      caries is not inevitable after gingival recession, but a small number of patients
      show a propensity for development of new lesions. Several risk factors have been
      identified. Thorough prophylaxis is essential for accurate diagnosis of root
      caries lesions, and radiographs can identify lesions which would otherwise be
      difficult to detect. The activity of any particular lesion can only be evaluated
      by observation at successive examinations. Fluoridated water may have a role in
      the prevention of root caries, but the evidence is not conclusive. Other forms of
      topical fluoride have been demonstrated to be effective. Cleansable and
      accessible lesions can be arrested with good oral hygiene and topical fluoride
      therapy. Teeth which require restoration may be restored with GIC, but
      limitations of the material make this unsuitable for all but readily accessible
      lesions, or where margins are supragingival. Clinicians should not rely on the
      fluoride released from GIC in situations where another material may provide a
      better restoration; in many situations, amalgam may be the material of choice.
      The longevity of bonded amalgam restorations has not been established, and
      conventional methods of amalgam retention remain a requirement of every
      restoration.

PMID- 8278120
TI  - Surgical face masks: protection of self or patient?

PMID- 8278121
TI  - Ethical concerns of nutritional life support.

PMID- 8278122
TI  - Healthcare reform--where are we now?

PMID- 8278123
TI  - Benchmarking MIS performance.

PMID- 8278124
TI  - Duty to communicate--"doctor notified".

PMID- 8278125
TI  - Nurse manager recruitment and retention. American Organization of Nurse
      Executives.

PMID- 8278126
TI  - Strategic planning: a road map to the future.
AB  - The strategic planning process enables the nurse executive to create a climate in
      which the nursing staff can participate freely in identifying and implementing
      needed changes. Because rapid change is a relatively recent development in
      healthcare, many are not prepared to cope effectively. Following a needs
      assessment and internal analysis, a collaborative process was used to define the
      values and culture needed for the hospital to achieve its vision. Six
      implementation strategies are discussed.

PMID- 8278127
TI  - Development of the American Board of Nursing Specialties (1991-1993).
AB  - A peer review program for specialty nursing certification has been developed by
      12 charter member groups. Its purpose is to serve as an advocate for consumer
      protection, to increase the public's awareness of the meaning and value of
      specialty nursing certification and to enhance prestige, self-actualization and
      professional advancement of certified nurses. The rationale for development of
      the organization and procedures for initiating membership are described.

PMID- 8278128
TI  - Implementation of a salary model for staff nurses.
AB  - A shift to a salary model for staff nurses was piloted on one unit of a 717-bed
      tertiary care teaching hospital. The assumption was that this would promote job
      satisfaction, professionalism, schedule flexibility and autonomy. A literature
      search, consultant input and a visit to a hospital using a salary model provided
      background for development and initiation of a six-month pilot study.

PMID- 8278129
TI  - Supporting ethnic and cultural diversity in nursing staff.
AB  - Especially in California, there is a growing need to match the ethnic and
      cultural profiles of nurses and patients. Two Bay Area healthcare programs pooled
      financial and human resources to develop long-range strategies aimed at
      increasing the number of minority graduate nurses. Included were a work-study
      program, a Russian immigrant nurse training program and a scholarship program for
      minority students. A Cultural Diversity Enhancement Committee is very active and
      various educational offerings have emerged from the Nursing Education and
      Research Department.

PMID- 8278130
TI  - Advancing clinical excellence: competency-based patient care.
AB  - A competency-based patient care program was developed to measure current levels
      in staff nurses. Use of evaluative tools designed on site has resulted in: 1)
      Development of a credentialing and privileging process which meets JCAHO
      requirements; 2) Planning of an educational calendar based on identified needs;
      3) Strengthening the foundations of the nursing career ladder; 4) Overall team
      building which integrates nurses with other healthcare professionals; and 5)
      Improved patient care.

PMID- 8278131
TI  - Evolution of a patient education program in a rural hospital.
AB  - An interdisciplinary Patient Education Committee developed strategies which would
      ensure adequate and consistent patient education. Four major projects merged: 1)
      a Patient and Family Teaching Policy; 2) in-house development of teaching
      handouts; 3) a Patient Education Television network, and 4) a Patient Education
      Materials list available on the Hospital Information System. Soon all teaching
      handouts will also be available in that format.

PMID- 8278132
TI  - Inadequate pain management: ethical considerations.
AB  - Many reports have documented that management of pain is often inadequate. Some
      reasons for this are explored: lack of knowledge on the part of the healthcare
      team, insufficient understanding of the significance of appropriate pain
      management, communication difficulties between patients and providers about pain,
      and concerns about medication side effects. Knowledge of four basic ethical
      principles can be an asset in pain management decisions.

PMID- 8278133
TI  - Collaborative management: revitalizing an OR.
AB  - Empowerment can promote a feeling of ownership, a necessary prerequisite for
      continuous improvement. Through this philosophy, a community hospital operating
      room manager began shifting responsibilities to the OR teams and leaders,
      resulting in a renewed sense of control and team management.

PMID- 8278134
TI  - Resolving conflict in a multicultural nursing department.
AB  - As a result of the turn toward recruitment from overseas in the 1980s, various
      challenges must be met and obstacles overcome to achieve harmony among
      multicultural staffs. A program was implemented to address volatile multicultural
      issues as part of the Nursing Incentive Reimbursement Award project in New
      Jersey. Nurses who participated in this sensitive program gave positive feedback,
      generally reporting that awareness was raised and collegial relationships
      improved. Specific interventions for dealing with a multicultural staff are
      offered.

PMID- 8278135
TI  - Patient satisfaction in home care/hospice.
AB  - Over the past 10 years, home healthcare has grown to include IV therapy and
      parenteral nutrition as well as patient education and dressing changes. In
      addition, other aspects of patient care--occupational, speech and physical
      therapy--can be provided under certain Medicare criteria. A patient satisfaction
      survey provides quantitative data to measure and assess home healthcare outcomes
      and to integrate results into a Quality Assurance program.

PMID- 8278136
TI  - Is it practical to change specialty areas?

PMID- 8278137
TI  - "Code Gray": a unique response.

PMID- 8278138
TI  - Learning from the future.

PMID- 8278139
TI  - Medicolegal climate for obstetrician-gynecologists.

PMID- 8278140
TI  - Transcervical tubal cannulation: a review.
AB  - Rapid progress has been made in the last 10 years regarding minimally invasive
      access to the human fallopian tube. Coaxial catheter systems are being used with
      hysteroscopy, fluoroscopy, ultrasonography, and tactile sensation to cannulate
      the fallopian tube transcervically with consistent success. Uterotubal
      obstruction viewed at the time of hysterosalpingogram can often be successfully
      cannulated with intrauterine pregnancies resulting. This review surveys all
      available published series of transcervical tubal cannulation with discussion of
      methodology, success in establishing patency, and the resultant pregnancy rates.
      It also describes how this technology has been applied to the intratubal
      deposition of gametes and embryos, direct visualization of the tubal epithelium,
      (falloposcopy), and contraception. Collectively, these techniques are defining
      tubal pathology more precisely, allowing us to prescribe the proper therapy.

PMID- 8278141
TI  - Basic concepts in molecular (DNA) diagnosis.
AB  - There has been an explosion of new information in molecular biology that will
      change the ways in which we practice medicine in the future. These laboratory
      advances in disease detection at the DNA level are quickly finding clinical
      application in prenatal diagnosis. An understanding of some basic concepts of DNA
      laboratory techniques and their applications is increasingly important in
      obstetrics and gynecology today.

PMID- 8278142
TI  - Basic concepts in biochemical antenatal diagnosis.
AB  - The biochemical test for each inherited metabolic disorder is unique. Each is
      complex and requires considerable experience for proper interpretation. All have
      inherent pitfalls that can be exaggerated by improper test procedures or
      inadequate tissue samples. An accurate prenatal diagnosis depends on having a
      reliable assay, competently performed, using a well-prepared sample.

PMID- 8278143
TI  - Prenatal cytogenetic analysis of the fetus.
AB  - A number of different cell sources can be used for prenatal cytogenetic analysis,
      the most common being chorionic villi and amniotic fluid. Analysis can be done at
      any time between 9 weeks' gestation and term. Depending on the cell source and
      type of analysis required, the laboratory will take anywhere from 24 hours to 2
      weeks to complete the study.

PMID- 8278144
TI  - Maternal serum screening for aneuploidy and open fetal defects.
AB  - The application of population-based maternal serum screening to prenatal
      diagnosis has been shown to be practical and is now wide-spread. It has been
      estimated that more than 40% of genetics programs in the United States that offer
      second trimester maternal serum screening now use at least one analyte in
      addition to AFP (Dr. George J. Knight, personal communication). The studies
      described here suggest that additional refinements in maternal serum screening
      are not only possible but inevitable. The use and interpretation of the analytes
      AFP, uE3, and hCG continue to be examined and expanded upon (Table 1). In the
      future, it seems logical that other analytes may be added or may replace one or
      more of these currently used markers. We have demonstrated that with AFP, uE3,
      and hCG, a separate protocol will identify a significant portion of trisomy 18
      fetuses with a minimal increase in the number of amniocenteses performed. Other
      significant aneuploidies, including Turner syndrome and triploidy, will be
      identified in screening for Down syndrome and trisomy 18. Although separate
      screening protocols for the detection of Turner syndrome and triploidy would not
      be of practical value, their detection within a screening protocol for Down
      syndrome is an added benefit and increases the value of the screening markers.
      The use of first trimester screening is being investigated. Although earlier
      diagnosis is attractive, routine first trimester screening for aneuploidy would
      necessitate the creation of an entirely new protocol for the collection of
      maternal serum samples and their interpretation, as well as a second round of
      screening for open fetal defects during the early second trimester. In contrast,
      an advantage of the current protocols is that screening for both types of
      abnormalities is possible using the same serum sample. Although research may
      eventually demonstrate that first trimester screening is technically feasible, an
      evaluation of the logistics of such screening may show it to be impractical.
      Obstetric implications of elevations and decreases in the new serum markers have
      not yet been studied carefully. It is logical, however, that just as with
      abnormal AFP (not explainable on a genetic basis), extreme levels of uE3 and hCG
      may also be associated with particular obstetric problems. Information on such
      deviations in analyte levels is just beginning to emerge. Finally, the study of
      maternal serum markers may contribute to an understanding of placental function
      in the second trimester, and ultimately advance our understanding of the
      underlying pathophysiologies of various fetal chromosomal and morphologic
      defects.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8278145
TI  - Ultrasonic clues to the detection of chromosomal anomalies.
AB  - The ultrasonic detection of fetal anomalies may well be the most challenging
      aspect of diagnostic ultrasound and, because ultrasonic clues to a chromosomal
      anomaly may be subtle, much depends on high quality ultrasound. Although
      difficult, the field is exciting and rewarding. It is hoped that recognition of
      the various common manifestations of chromosomal anomalies described in this
      article will increase the number of chromosomal anomalies detected and ameliorate
      the consequences of these disorders.

PMID- 8278146
TI  - Prenatal diagnosis of congenital heart disease.
AB  - In counseling the patient with a fetus with CHD, attempts should be made to
      determine the exact cardiac diagnosis and whether there are associated
      extracardiac or chromosomal abnormalities. A careful family history and
      examination of appropriate family members may lead to the diagnosis of a genetic
      syndrome. An evaluation of the maternal medical and obstetric history will
      explore the possibility of maternal disease states, teratogens, or environmental
      exposures as cause for the cardiac lesion. The information obtained from a
      prenatal evaluation may lead to a possible cause of CHD in the fetus and thus
      more accurate counseling regarding recurrence risks and the prognosis for the
      present pregnancy. With further improvement in the prenatal diagnosis of
      structural cardiac disease, a knowledge of possible causes is essential for the
      clinician providing counseling. In addition, a multidisciplinary approach with
      the involvement of obstetricians, neonatologists, pediatric cardiologists,
      cardiac surgeons, and geneticists will optimize care in pregnancies complicated
      by a fetus with structural heart disease.

PMID- 8278147
TI  - Genetic amniocentesis and chorionic villus sampling.
AB  - With the expanding list of prenatally detectable disorders, increasing numbers of
      patients are presented with the option of invasive prenatal diagnosis. Care
      providers need to address questions regarding the safety and accuracy of these
      procedures, as well as the indication. This article reviews these issues for
      genetic amniocentesis and chorionic villus sampling.

PMID- 8278148
TI  - Mosaicism in chorionic villus sampling.
AB  - Although chromosomal mosaicism is encountered frequently in CVS, it is most often
      restricted to the extraembryonic tissues. Counseling before CVS should include a
      discussion of the frequency and significance of placental mosaicism. Patients
      seeking information about the procedure need to be aware of the slight but not
      negligible possibility of the need for additional follow-up studies. Additional
      studies may involve additional risks with emotional and psychological sequelae.
      Ultimately, no prenatal procedure or combination of procedures can provide 100%
      accuracy in excluding mosaicism once the issue has been raised. When the
      mosaicism is felt to be confined to the placenta, counseling should probably
      address the potential increased risk for pregnancy complication, such as
      miscarriage and IUGR, with appropriate follow-up of the pregnancy, especially in
      the third trimester. Excluding the issue of mosaicism, the predictive value of
      cytogenetic diagnosis after CVS is equivalent to that of amniocentesis. In
      addition, CVS provides this information at an earlier time in the pregnancy than
      does amniocentesis. The majority of patients electing CVS (98% or more) will not
      have to deal with these complicated issues. It is hoped that an increasing
      cumulative experience with CVS mosaicism will help differentiate low- from high
      risk situations. At the present time, however, there are insufficient and
      inconsistent data with which to accurately assess the risks associated with
      placental mosaicism. Most of the available literature concludes that additional,
      more focused studies, including long-term follow-up, are needed to help elucidate
      a better understanding of these issues.

PMID- 8278149
TI  - Fetal blood sampling.
AB  - Fetal blood sampling is accepted and widely practiced by experienced
      perinatologists. Its facile and safe access to the fetal circulation has
      broadened the spectrum of congenital disorders diagnosed prenatally. Some fetal
      disease states can now be identified and treated earlier, directly, more quickly,
      and more effectively than before, resulting in improved patient care. The volume
      of fetal blood to be retrieved and collection media for blood (Table 7) will be
      dictated by the indication for the procedure and thus the desired laboratory
      tests. These items and the preferred sampling site should be planned in advance
      by the operator. However, a flexible approach to fetal blood sampling should be
      maintained, anticipating the variability of fetal positions, cord insertions, and
      ultimate specimen volume. Teamwork among the perinatologist, sonographer,
      laboratory, and patient will continue to expand the role of fetal blood sampling
      in obstetrics.

PMID- 8278150
TI  - Embryoscopy and fetoscopy.
AB  - The introduction of transabdominal fiberoptic thin-gauge visualization of the
      embryo or fetus in the first trimester allows an earlier diagnosis of congenital
      anomalies currently beyond the resolution of ultrasound. In addition, it has the
      true potential of providing access to the fetal circulation at an early age, an
      accomplishment that would have enormous diagnostic and therapeutic implications.
      In the second and third trimester, operative fetoscopic techniques promise to
      open a new frontier in the diagnosis and management of fetal surgical and medical
      conditions.

PMID- 8278151
TI  - Fetal cells in the maternal circulation. Technical considerations for practical
      application to prenatal diagnosis.
AB  - Recent advances in cell separation technology and DNA analytic techniques leave
      little doubt as to the presence of fetal cells in the maternal circulation. The
      potential of using these cells for genetic analysis is compelling. The practical
      aspects of establishing a universal method utilizing the new capabilities in
      clinical practice have not been addressed to date. The major hurdles that still
      need to be traversed before this technology is universally adopted include the
      identification of appropriate sampling and separation methods yielding fetal
      cells amenable to genetic analysis by rapid DNA technologies, clinical studies of
      appropriate statistical power to validate and compare this approach to current
      genetic testing, and comparison of this approach to other noninvasive paradigms
      such as triple screening. Despite the tremendous value of noninvasive genetic
      screening, the rigorous course required to progress from description of
      scientific capability to validation of a clinical test must not be ignored or
      rushed for financial considerations.

PMID- 8278152
TI  - Preimplantation prenatal diagnosis.
AB  - Preimplantation prenatal diagnosis refers to the application of molecular genetic
      techniques to the assessment of gametes before conception or to early embryos
      before implantation. Such techniques could allow couples at significant risk for
      a variety of known genetic diseases to use assisted reproductive technology in
      achieving pregnancies that are free of the genetic disorder in question. The
      techniques, their risks, benefits, limitations, and potential applications are
      described, and recent experiences with human pregnancies are reviewed.

PMID- 8278153
TI  - Prenatal application of somatic gene therapy.
AB  - Somatic gene therapy in the fetus or neonate represents an exciting new approach
      for the management of some congenital or inherited diseases. It is likely that
      clinical trials of these methods will take place in the future. In contrast,
      despite the potential for manipulation of embryos and inherited genetic material,
      the clinical applicability of these methods is uncertain.

PMID- 8278154
TI  - Swivel arm perimeter for visual field testing in different body positions.
AB  - To investigate the influence of body position on visual field results, a 'swivel
      arm perimeter' was built, based on a modified Octopus 1-2-3. Here, the measuring
      unit was detected from the control unit and mounted on a swivel arm, allowing its
      movement in all directions. The first results obtained with this device have
      indicated that its development was worthwhile.

PMID- 8278155
TI  - Choroidal melanomas near the optic disk or macula. Long-term results after proton
      beam irradiation: a report of 3 cases.
AB  - Three patients with choroidal melanomas of the posterior pole were treated with
      proton beam irradiation. One tumor was medium-sized, two were large-sized. Two of
      the three eyes were functionally single eyes. 60 CGE (cobalt gray equivalents)
      was delivered in 4 equal treatments during 4 consecutive days. The minimum follow
      up period for each patients is 4 years, the average time 4.8 years. Functionally,
      we lost both eyes with the large-sized tumors owing to severe radiogenic side
      effects; the eye containing the largest tumor had to be enucleated after 48
      months because of phthisis bulbi. No metastases have developed up to now.

PMID- 8278156
TI  - Elschnig's spots as a sign of severe hypertension.
AB  - Elschnig's spots were observed in 3 patients with severe hypertension. Extensive
      choroidal depigmentation as well as hyperpigmentation surrounded by
      depigmentation were scattered over the whole retina. At the periphery, Siegrist's
      bead string pigmentation was present (first patient). Despite the massive
      chorioretinal changes, only slight functional changes were evident. The retinal
      hypertensive changes predominated over choroidal vascular lesions (second
      patient). Elschnig's spots were present almost only unilaterally (third patient).
      Choroidal vascular changes predominated in the presence of acute hypertension
      (first and third patient), whereas retinal vascular changes were the result of a
      more gradual onset of hypertension (second patient).

PMID- 8278157
TI  - Echographic and ophthalmodynamometric study in the empty sella syndrome.
AB  - A group of patients with empty sella syndrome (ESS) and visual field defect with
      or without visual loss has been examined with standardized echography and
      ophthalmodynamometric examination. The optic nerve thickness has been evaluated
      with standardized echography; the pressure of the central retina artery has been
      evaluated with ophthalmodynamometric examination with or without compression on
      the external carotid. Our results point out two different pathogeneses in the
      ESS: vascular defects or irregular endocranial hypertension.

PMID- 8278158
TI  - [Influence of Long-Term Stimulation on Pattern-Reversal Visual Evoked Cortical
      Potentials].
AB  - In 20 subjects, we recorded the pattern-reversal visual evoked cortical potential
      (VECP) over a period of 30 min. We could not find any remarkable alterations of
      the peak times, they were unchanged over the time. During the first 10 min, the
      amplitudes showed a clear tendency to decrease if one evaluated the averaging
      value of the whole group. After this time, there were no significant changes. But
      we learned a quite different behavior of amplitudes evaluating the record of each
      subject. We found 5 types of different behavioral modulated responses. The
      problems of long-term investigation are sophisticated and need further
      investigation to learn which different factors have an impact on VECP. From a
      clinical point of view, a long-term investigation shows no relevant potential
      alterations.

PMID- 8278159
TI  - Intraoperative suspension-recession technique for treatment of vertical
      strabismus in thyroid myopathy.
AB  - Ten patients underwent extraocular muscle surgery with an intraoperative
      suspension-recession technique for diplopia induced by vertical strabismus in
      thyroid myopathy. The average ratio of the reduction of vertical deviation to the
      amount of surgery was 1.8 degrees/mm (range, 1.0 degrees/mm-2.8 degrees/mm).
      Eight (80%) patients had single binocular vision restored in the primary position
      without prism or compensatory torticollis after surgery. One patient who showed
      evidence of abnormal thyroid function at surgery developed an overcorrection
      postoperatively.

PMID- 8278160
TI  - Do beta-blockers cause vasospasm?
AB  - The action of beta-blockers on papillary blood flow is quite controversial.
      Because there is a known relationship between digital and ocular vasospasm, we
      measured digital blood flow by laser-Doppler methods as a peripheral index of
      ocular vasospastic disorders. Thus, the effects of cardioselective (betaxolol)
      and noncardioselective (timolol) beta-blockers on peripheral blood flow in
      healthy volunteers were evaluated. Neither beta-blocker lowered peripheral blood
      flow; for betaxolol, there was even a significant increase compared to no
      medication. No significant differences between betaxolol and timolol were seen.

PMID- 8278161
TI  - Malignant melanoma in ten-month-old patient diagnosed by magnetic resonance
      imaging.
AB  - Here we report a case of choroidal malignant melanoma in a 10-month-old child,
      who has cafe-au-lait spots on the abdomen. She had suffered from enlargement of
      the eyeball since 5 months old due to a tumor-like mass in the vitreous cavity.
      It was examined with slitlamp biomicroscopy, indirect ophthalmoscopy, orbit
      computerized tomography and magnetic resonance imaging (MRI). Retinoblastoma or
      neurofibroma was suspected from the clinical diagnosis, and from the tomographic
      point of view, it could be choroidal hemangioma, however, the MRI study,
      unexpectedly suggested the possibility of choroidal malignant melanoma, and it
      could be confirmed by the results of a histopathologic examination.

PMID- 8278162
TI  - Velocity profile of human horizontal saccades.
AB  - To assess saccadic trajectories, we evaluated the velocity profile using the
      'skewness ratio' (the proportion of acceleration time to total saccadic duration)
      as a parameter. Horizontal cross-center saccades against target movements of 10
      degrees, 20 degrees and 30 degrees were measured in 6 normal subjects using the
      magnetic search coil method. As the amplitude increased the period of the
      deceleration phase became prolonged: 10 degrees saccades were almost symmetrical
      and 30 degrees saccades were skewed to a ratio of about 0.3. A close relationship
      between duration and skewness ratio was found, and the skewness ratios of
      temporal saccades were smaller than nasal ones. This skewness ratio would be a
      useful parameter for assessing the velocity profile of human saccades.

PMID- 8278163
TI  - Ophthalmologic findings in biotinidase deficiency.
AB  - Biotinidase deficiency is an autosomal recessively inherited metabolic disorder
      characterized by neurological and cutaneous manifestations and metabolic
      abnormalities. We studied 78 symptomatic children and found that 51% had
      ophthalmologic abnormalities. These include infections (30%), optic neuropathies
      and visual disturbances (13%), motility disturbances (13%), retinal pigment
      changes (4%) and pupillary findings (1%). The most commonly reported findings are
      optic atrophy and keratoconjunctivities. Although the disorder can be effectively
      treated with biotin therapy, untreated children are at risk of developing
      permanent neuro-ophthalmic damage.

PMID- 8278164
TI  - Contrast sensitivity in ocular hypertension and glaucoma.
AB  - Forty-eight patients aged from 60 to 69 years (58 eyes) with ocular hypertension
      (OHT) or primary open-angle glaucoma (POAG) and a control group of 16 persons of
      the same ages (26 eyes) were studied with a clinical contrast sensitivity test,
      the Vistech 6500 test. No significant differences could be found between the
      normal and OHT or POAG eyes in any of the spatial frequencies. The group of newly
      found POAG eyes showed the greatest difference from the normals, but this
      difference did not reach the level of significance in any of the spatial
      frequencies.

PMID- 8278165
TI  - Laser treatment of iris vascular tufts.
AB  - We describe a case of iris vascular tufts which came to our attention because of
      a hyphaema. Laser treatment was carried out for the vascular anomalies. After a
      period of 3 months, fresh vascular anomalies had appeared in different locations.
      Further treatment led to permanent obliteration. We emphasize the importance of
      fluoro-iridography in the monitoring of vascular anomalies as it allows accurate
      targeting treatment.

PMID- 8278166
TI  - Pathology of corneal endothelium in keratoconus.
AB  - Keratoconus is characterized by stromal thinning and conical deformity of the
      cornea that affects a small but significant portion of the population. Although
      keratoconus has been well studied, endothelial changes have not been extensively
      investigated. We studied the endothelium of 14 keratoconus corneal buttons
      obtained over the past 6 years by penetrating keratoplasty using light
      microscopy, scanning electron microscopy and transmission electron microscopy.
      Observations were correlated with patient history. Corneas demonstrated:
      endothelial cell pleomorphism and polymegathism (6 corneas); endothelial cell
      degeneration (13), and evidence of anterior chamber inflammation (4). Patterns of
      endothelial damage were variable ranging from isolated cell membranolysis to
      denudement of Descemet's membrane. Less damage was present at the apex of the
      cones than that observed in a circumferential pattern at the bases. In general
      the damage observed correlated with the severity and duration of the keratoconus
      with 9 years being the dividing time between mild and severe endothelial cell
      damage. These observations support other studies that implicate contact lens wear
      as a cause of pleomorphism and polymegathism in these patients. Endothelial cell
      alterations are likely a secondary event occurring due to mechanical stresses.

PMID- 8278167
TI  - Retinal phakomata associated with cerebral astrocytoma. An incomplete form of
      Bourneville-Pringle disease?
AB  - We report on a 21-year-old, male patient with unilateral retinal phakomata
      associated with histologically proved cerebral astrocytoma. The patient had
      presented with bilateral loss of vision and a left-sided hemiparesis.
      Ophthalmoscopy showed bilateral optic nerve atrophy, multiple punched-out areas
      of depigmentation and astrocytic hamartomata in the right eye. Despite the
      absence of classic signs of Bourneville-Pringle disease such as adenoma sebaceum,
      epilepsy and mental retardation, a strongly presumptive diagnosis of tuberous
      sclerosis could be made. This unusual case demonstrates that retinal phakomata
      can be the solely visible manifestation of Bourneville-Pringle disease.

PMID- 8278168
TI  - Postpartum Candida endophthalmitis treated with fluconazole.

PMID- 8278169
TI  - Intraocular pressure-dependent progression of visual field loss in advanced
      primary open-angle glaucoma: a 15-year follow-up.
AB  - We studied the relationship between intraocular pressure (IOP) and progression of
      visual filed loss in 83 eyes of 83 patients with advanced primary open-angle
      glaucoma (loss of at least one quarter of the visual field on Goldmann
      perimetry). During the 15-year follow-up study, 71 eyes (86%) showed progression
      of visual field loss. The mean IOP was significantly lower in eyes that remained
      stable (13.4 +/- 1.3 mm Hg) than in those that showed progression of visual field
      loss (19.4 +/- 2.6 mm Hg). These results suggest that it is necessary to reduce
      IOP to below 15 mm Hg to prevent further progression of visual filed loss in
      advanced glaucoma.

PMID- 8278170
TI  - Correlation of electroretinographic changes with visual prognosis in central
      retinal artery occlusion.
AB  - Recent advances in the treatment of central retinal artery occlusion (CRAO) have
      resulted in a relatively good prognosis, but few studies have been reported. In
      the present study, electroretinography (ERG) was used to evaluate visual function
      recovery in 15 cases of CRAO. All patients were treated with ocular massage,
      intravenous urokinase and hyperbaric oxygenation. Of 15 cases, 8 had improved
      vision after treatment. A single flash ERG of 40 J from a xenon lamp was recorded
      before and during treatment. For ERG evaluation, the a- and b-wave amplitudes and
      the b/a wave amplitude ratio were analyzed. As control, the nonaffected eye of
      each patient was used. Before treatment, no significant difference was found in
      the a-wave amplitude between the two eyes, while a significant attenuation was
      found in the b-wave of the affected eye (p < 0.01). The b/a ratio was 0.73 +/-
      0.04 (mean +/- SE) in the affected eye group and 1.08 +/- 0.03 in the nonaffected
      eye group. It was significantly higher (p < 0.01) in eyes with improved visual
      acuity (0.83 +/- 0.03) than in those with unimproved visual acuity (0.62 +/-
      0.05). The b-wave amplitude increased in accordance with visual improvement. We
      could thus demonstrate the temporal changes of ERG before and after treatment and
      show their correlation with the visual prognosis in patients with CRAO.

PMID- 8278171
TI  - Recurrence of nanophthalmic uveal effusion.
AB  - A patient with nanophthalmic uveal effusion had a recurrence 7 months after the
      initial sclerectomies and sclerostomies. The effusion was cured by repeating the
      procedure. Specimens obtained at the first operation showed interlacing collagen
      lamellae and thin collagen bundles with an electron-dense deposit in the
      perifibrillar space. Specimens from the second operation showed disarranged
      collagen bundles with closely packed thin collagen fibrils. Collagen lamellae
      were not found. The regenerated scleral tissue was thought to interfere with the
      transscleral outflow and to block the bypass route, thus resulting in the
      recurrence of uveal effusion.

PMID- 8278172
TI  - C-wave study in cone dysfunction syndrome.
AB  - An electroretinogram (ERG) and C-wave were recorded from 15 patients suffering
      from cone dysfunction syndrome. Our results show that the photopic ERG was
      diminished with extinction of the oscillatory potentials. On the other hand, the
      mean value of the C-wave amplitude was diminished and the implicit time
      prolonged. This may serve as a further diagnostic sign of the disease.

PMID- 8278173
TI  - A new focal pattern stimulator under direct observation of ocular fundus.
AB  - A new focal pattern stimulator was developed. Since this system enables direct
      observation of ocular fundus during examination, it may be useful for the
      objective assessment of visual function in patients with various kinds of eye
      diseases.

PMID- 8278174
TI  - Silent myocardial ischemia in glaucoma patients.
AB  - The pathophysiological mechanism involved in normal-tension glaucoma is still not
      fully understood. Besides intraocular pressure, vascular and rheological factors
      have been described. In the present study, the prevalence of silent myocardial
      ischemia in patients of the same age with normal-tension glaucoma, primary open
      angle glaucoma and cataract was compared. Our findings indicate that in all three
      groups ischemic episodes occurred more frequently than described in normal
      people. The most striking observation, however, was the fact that in normal
      tension glaucoma the frequency was twice that of the other two groups.

PMID- 8278175
TI  - Foveal avascular zone in idiopathic juxtafoveolar telangiectasia.
AB  - We measured angiographically the foveal avascular zone (FAZ) in 26 subjects with
      idiopathic juxtafoveolar telangiectasia (IJFT) and 27 control subjects.
      Quantitatively, FAZ was significantly smaller in IJFT (median = 0 mm2) than in
      controls (median = 0.405 mm2). Qualitatively, the telangiectasia in IJFT was
      temporal (92.5% of eyes) and appeared as microaneurysms interconnected with
      several capillaries, spider-shaped microaneurysms, or Coats'-like telangiectasia.
      IJFT is characterized by temporal telangiectasia and small FAZ.

PMID- 8278176
TI  - Walker-Warburg syndrome: a report of 3 cases.
AB  - Walker-Warburg syndrome is a congenital malformation syndrome of unknown etiology
      which is characterized by fatal neurological lesions. It was first described by
      Walker in 1942 as involving agyria, hydrocephalus and eye malformations. Its
      etiology has been discussed in all of the articles on the subject in the
      literature, but the majority of the authors describe it as an autosomal recessive
      syndrome. Ultrasonography plays a key role in detecting a cephalic anomaly by
      prenatal diagnosis as in our 2 cases. The aim of this article is to report 3 new
      cases of Walker-Warburg syndrome in two families. Knowledge of this syndrome
      emphasizes both the need for ultrasonographic observation and genetic counselling
      for families at risk.

PMID- 8278177
TI  - Ocular growth in the fetus. 1. Comparative study of axial length and biometric
      parameters in the fetus.
AB  - The knowledge of ocular growth during fetal life, when compared with other fetal
      biometric parameters, could not only provide a better definition of malformation
      syndromes but could also give a better understanding of certain pathological
      processes in premature babies and in newborns. As the literature concerning
      prenatal ocular dimensions contains few data, the aim of this study was to
      measure the axial length of the globe (AL) in fetuses and compare this
      measurement with their gestational age, weight, height, head circumference (HC)
      and thoracic circumference (TC) in order to compile a reference table. In the
      present study, 76 globes from 38 fetuses (18-41 weeks gestational age) from the
      Department of Pathology (Timone University Hospital, Marseille) were examined.
      Ultrasonography A and B were used to measure the AL, and a pathological
      examination determined fetal weight, HC, TC and height. We were interested to
      find out which of the parameters studied would give the best correlation with
      ocular growth. Statistical analysis showed that HC remained the most discriminant
      factor and correlated best with ocular growth. We thus obtained an equation for
      ocular size according to HC that could serve as a basis for detecting pre- or
      postnatal ocular defects.

PMID- 8278178
TI  - Ocular growth in the fetus. 2. Comparative study of the growth of the globe and
      the orbit and the parameters of fetal growth.
AB  - In a previous study, we showed that the growth of the eye during fetal
      development compared with the other parameters of the fetus was above all
      connected to the head circumference, which appeared to be the most discriminant
      measurement. In a second study, we measured the growth of the orbit of the fetus
      in order to compare it with the growth of the globe and the cranial
      circumference. Another 60 eyeballs of 30 fetuses of 18-41 weeks gestational age
      were examined. The corneal diameter (CD) of the cornea was a measurement added to
      those used in the method in the previous study, and orbital radiography was
      carried out: the parameters used were the same as in the previous study measured
      in relation to the CD, orbital diameter (OD) and the biparietal diameter (BPD).
      The aim of this study was to show the links between the variations in the
      measurements and to estimate them in relation to fetal growth. The results
      confirm those of the previous study, and this study also shows that, in
      estimating the head circumference, the OD and CD are the most accurate
      indicators. This study was also concerned with the BPD: the best correlation is
      obtained with the OD, which can be estimated accordingly from the BPD. Although
      the OD is not in an area studied by ultrasonography (highly dependent on the
      sectional plane), this study shows that it should perhaps be reconsidered in the
      prenatal diagnosis of orbital malformation. It would then be necessary to take
      into account not only the BPD but also the relationship between the OD and the
      BPD.

PMID- 8278179
TI  - Combined local excision and brachytherapy with ruthenium-106 in the treatment of
      epibulbar malignancies.
AB  - Two patients with epibulbar malignancies were treated by local excision and
      brachytherapy with ruthenium-106. One patient showed a large melanoma on the
      epibulbar conjunctiva, the other patient suffered from a recurrent squamous cell
      carcinoma at the limbus. After excision of the tumor including lamellar
      sclerectomy and keratectomy, a ruthenium-106 plaque was sutured to the sclera,
      and a total dose of 290 and 320 Gy, respectively, was delivered to the tumor bed.
      No severe radiogenic complications were observed except for a rarefaction of the
      sclera in the treatment area and a slow cataract increase. After a follow-up
      period of 50 and 22 months, respectively, both patients do not show any
      recurrence or metastatic disease.

PMID- 8278180
TI  - Treatment of uncomplicated cases of rhegmatogenous retinal detachment with an
      expanding gas bubble.
AB  - We reviewed 55 consecutive cases of rhegmatogenous retinal detachment treated
      with pneumatic retinopexy as a primary procedure and followed up for a minimum of
      1 year. 40 eyes were phakic, 11 aphakic and 4 pseudophakic. 0.6 ml of sulfur
      hexafluoride were injected into 42 eyes, while 0.3 ml of perfluoropropane were
      introduced into 13. Transconjunctival cryotherapy was performed in 51 eyes, while
      light coagulation was used as retinopexy after the retina was reattached in the
      remaining 4 cases. Of the 55 eyes undergoing treatment, 46 (83.6%) retinas were
      reattached with one operation. The benefits, complications and disadvantages of
      the procedure are reported.

PMID- 8278181
TI  - Computer-assisted interpretation of resolution visual fields from patients with
      chiasmal and retrochiasmal lesions.
AB  - Computer-assisted interpretation of resolution visual fields was performed in 147
      normal subjects and 174 consecutive patients with known chiasmal or retrochiasmal
      lesion. The program identified 99% of normal subjects, and provided support for
      the correct diagnosis in 64% of patients with chiasmal and 83% of patients with
      retrochiasmal lesions. In conclusion, computer-assisted interpretation of
      resolution visual fields can provide considerable support to the final diagnostic
      decision in patients with lesions of the visual pathways.

PMID- 8278182
TI  - Evaluation of the Tono-Pen 2 and the X-Pert noncontact tonometers in cataract
      surgery.
AB  - The Oculab Tono-Pen and the X-Pert noncontact tonometers (NCTs) were compared to
      the Goldmann applanation tonometer in a consecutive series of 45 patients before
      and after cataract surgery. In the preoperative period, the mean value of the
      paired difference at intraocular pressure (IOP) measurements was -1.30 +/- 2.11
      mm Hg (mean +/- SD) for the X-Pert NCT (X-Pert NCT minus Goldmann) and -0.19 +/-
      2.56 mm Hg for the Tono-Pen 2 (Tono-Pen 2 minus Goldmann). In the postoperative
      period, this mean difference was 0.26 +/- 2.45 mm Hg for the X-Pert NCT and 0.87
      +/- 2.83 mm Hg for the Tono-Pen 2. We found 87 and 67% of the X-Pert NCT and the
      Tono-Pen 2 readings to be within +/- 2 mm Hg of the Goldmann readings,
      respectively. In both preoperative and postoperative eyes, correlation
      coefficients between the readings of the three instruments were high (ranging
      from 0.84 to 0.96). Differences between the three tonometers were not correlated
      with corneal thickness of corneal curvature postoperatively. Both Tono-Pen 2 and
      X-Pert NCT could thus be considered accurate instruments for IOP screening after
      cataract surgery when compared to the Goldmann applanation tonometer.

PMID- 8278183
TI  - Corneoscleral ulceration and corneal perforation after pterygium excision and
      topical mitomycin C therapy.
AB  - A 78-year-old woman complained of ocular pain in the right eye. Thirty-three
      months before, the patient had a pterygium excised and mitomycin C, 0.04%, was
      instilled 3 times a day postoperatively for 10 days in the right eye. The same
      surgery was performed and the same drug was used for a course of 5 days in the
      left eye. Corneoscleral ulceration and corneal performation occurred in the right
      eye. The lesions were successfully treated with a lamellar patch graft with
      reserved corneosclera. We believe that it may not be safe to instill 0.04%
      mitomycin C 3 times a day postoperatively for 10 days.

PMID- 8278184
TI  - Effect of uncorrected refractive errors upon central visual field testing.
AB  - An investigation of the effects of uncorrected refractive errors upon a central
      visual field examination has been made with a view to establishing what the
      likely effects would be of omitting a refractive correction when screening the
      visual field with a threshold related, supra-threshold strategy on the Henson
      CFA3000. The results indicate that, while a linear relationship exists between
      the extent of threshold elevation and the product of residual refractive error
      and pupil size, the scatter in the results means that accurate predictions cannot
      be made in individual cases. The threshold elevation was found to be independent
      of eccentricity (within the central 21 degrees from fixation) and did not
      increase the variability of results. These last two findings indicate that
      uncorrected refractive errors are unlikely to affect the sensitivity of the
      threshold related, supra-threshold strategy to localized visual field defects.

PMID- 8278185
TI  - Colour vision screening in children: an evaluation of three pseudoisochromatic
      tests.
AB  - We examined 513 children (258 boys and 255 girls), between 3 and 11 years of age,
      with three pseudoisochromatic tests which involve different visual tasks. These
      were a selection of numeral designs from the Ishihara test, the Ishihara test for
      Unlettered Persons and the Velhagen Pfugertrident test. Eighteen children were
      found to be colour deficient. The symbol designs of the Unlettered Persons test
      were found to be the quickest and most effective method for examining children
      under 7 years of age. After 7 years of age the symbol designs of the Unlettered
      test and the numeral designs of Ishihara test were equally effective. The
      preferred numeral designs for screening children with the Ishihara plates are
      listed. Verbal identification always produced the most accurate results. Drawing
      over the figures or selecting replicas increased the viewing time and assisted
      children with normal colour vision to see both figures in transformation designs,
      especially pathway designs. The Velhagen Pfugertrident test was found to be
      unreliable for colour vision screening and younger children had difficulty
      performing the figure matching task.

PMID- 8278186
TI  - TNO stereopsis test as an aid to the prevention of amblyopia.
AB  - In this investigation, carried out under a Youth Health Care postgraduate course
      in Nijmegen, the stereopsis of a school population of 730 children, aged 4-18
      years, was recorded and clinically evaluated. Stereopsis was measured using the
      TNO test, a random-dot stereo test especially designed for the early detection of
      amblyopia. The main aims of this study were to establish the validity of the TNO
      test as a screening test for amblyopia, obtain information about the variability
      and age dependence of stereopsis, and to evaluate the efficacy of amblyopia
      prevention. The most important findings can be summarized as follows: 1. All
      amblyopes are detected by the TNO test's recommended referral criterion of 240
      sec arc (binocular threshold parallax in sec arc). 2. The red-green anaglyphs
      used in the test do not pose problems for individuals with a colour vision
      deficiency. 3. The ability to discriminate depth improves by a factor of two over
      the age interval 4-12 years. 4. A stereoacuity of < or = 120 sec arc is a good
      predictor of normal or correctable normal vision, and may therefore help in
      evaluating the often incomplete results of eye tests of young children. 5. Where
      there is an increased perinatal risk, there is a greater chance of disturbed
      binocular vision. 6. It is estimated that 75% of amblyopes remain amblyopic,
      possibly because of delayed detection; 60% of the amblyopes in the population
      examined were not identified before the age of 5 years.

PMID- 8278187
TI  - Investigation of parameters influencing intraocular pressure increases during
      sleep.
AB  - In previous studies, we have observed that young normal subjects show an increase
      in intraocular pressure (IOP) after sleep. Here we describe three experiments
      which investigated: (i) the effects of sleep in five groups of subjects:
      glaucoma, suspect glaucoma, young high-normal IOP, old high-normal IOP groups and
      an elderly control group, (ii) the effect of exposure to bright light (2500 lux)
      during sleep on associated IOP changes, and (iii) the relationship between
      changes in IOP and plasma melatonin during sleep. For all experiments IOP was
      measured before and after sleep. We found that IOP increased significantly after
      sleep. There was also a significant difference between the five groups with the
      old high-normal group showing the greatest increase, and the young high-normal
      group showing the lowest increase in IOP. The increase in IOP after sleep was
      reduced when the same subjects slept in bright light compared to that recorded
      when subjects slept in the dark. Plasma melatonin levels, as well as IOP,
      increased after sleep in the dark although there was no correlation between these
      changes for individual subjects.

PMID- 8278188
TI  - Accommodative adaptation and age of onset of myopia.
AB  - Tonic accommodation in an empty field and accommodative adaptation, defined as
      accommodation shift after 2 min viewing of a 4 D near task, were measured using
      an infrared optometer. Subjects were classified into three types: emmetropes (n =
      18), early onset myopes (n = 18) and late onset myopes (n = 15). The relationship
      between accommodative adaptation and the onset age of myopia were compared. There
      was no statistical difference in the pre-task tonic accommodation among the three
      subject groups. However, the accommodative adaptation differed in the three
      groups during the 5 min post-task period. The average accommodative adaptation of
      emmetropia, early onset myopia and late onset myopia were 0.66, 0.27 and 1.19 D,
      respectively. Accommodative adaptation in the late onset myopia group was
      significantly higher than in the emmetropia group. Furthermore, the accommodative
      adaptation in the early onset myopia group was significantly lower than in the
      emmetropia group. Two possible aetiologies of myopia are discussed: one for the
      group which shows low accommodative adaptation that has no relationship with the
      age of onset and another for the group which shows high accommodative adaptation
      that has a relationship to an onset age of 15 years or later. The aetiology is
      also considered with regard to a potentiating chemical effect on the synapses of
      the ciliary muscle.

PMID- 8278189
TI  - Effect of filters on disability glare.
AB  - Disability glare is the reduction in visual performance caused by a peripheral
      glare source. We examined the effect of a long wavelength pass (red) and a short
      wavelength pass (blue) filter on disability glare in the presence of varying
      amounts of induced wavelength dependent stray light. Measurements were made in
      the absence of any filter and then repeated in the presence of the red and blue
      filters whose luminous transmission factors were equal relative to both the
      stimulus and the glare source. Neither of the filters had any effect on
      disability glare. Filters not only reduce the amount of veiling luminance from
      the glare source, but also reduce the ability to detect the stimulus. Disability
      glare was not significantly different with the red and blue filters, even in the
      presence of wavelength dependent scatter. Calculation of the veiling luminance
      transmitted by each filter revealed that the difference in veiling luminance in
      the two filter conditions was insufficient to result in a measurable difference
      in disability glare.

PMID- 8278190
TI  - Measurement of corneal topography in keratoconus.
AB  - A new method is described for calculating the topography and curvature of an
      irregularly shaped cornea. Vertical planes of light are projected onto the cornea
      and points in x, y, z space are calculated from the light images on the corneal
      surface. A matrix of points is produced on the cornea and a mathematical surface
      is fitted to them. Using differential geometry theory, curvature values are
      calculated to find the corneal apex position, apex curvature and curvature change
      away from the apex. Typical results, in the form of a contour map, are shown for
      normal corneas and corneas with mild to severe keratoconus. The method gives an
      accurate quantitative measurement of keratoconic and other irregular corneas.

PMID- 8278191
TI  - Optic disc interpretation in glaucoma: is confidence misplaced?
AB  - A photographic questionnaire has been used to investigate whether or not
      clinicians have realistic expectations of their ability to distinguish optic
      discs associated with glaucomatous visual field loss from discs of healthy eyes.
      The questionnaire consisting of 30 non-stereoscopic fundus photographs from 15
      patients was administered to 40 ophthalmologists of varying experience and 10
      optometrists. Each group displayed large discrepancies between their expected and
      achieved scores suggesting that clinicians may overestimate their ability to
      recognize the glaucomatous optic disc. This could lead to diagnostic errors
      especially in cases where tonometric and visual field parameters are considered
      equivocal. An over-reliance on the cup/disc ratio appeared to be the most likely
      cause of error.

PMID- 8278192
TI  - Binocular vision in a virtual world: visual deficits following the wearing of a
      head-mounted display.
AB  - The short-term effects on binocular stability of wearing a conventional head
      mounted display (HMD) to explore a virtual reality environment were examined.
      Twenty adult subjects (aged 19-29 years) wore a commercially available HMD for 10
      min while cycling around a computer generated 3-D world. The twin screen
      presentations were set to suit the average interpupillary distance of our subject
      population, to mimic the conditions of public access virtual reality systems.
      Subjects were examined before and after exposure to the HMD and there were clear
      signs of induced binocular stress for a number of the subjects. The implications
      of introducing such HMDs into the workplace and entertainment environments are
      discussed.

PMID- 8278193
TI  - Form and behaviour of Haidinger's brushes.
AB  - A computer simulation of Haidinger's brushes that is based on the optics of a
      radially symmetrical array of dichroic elements is presented. The simulation
      describes the perceived distribution of intensity and contrast of Haidinger's
      brushes when observed with monochromatic plane polarized light at different
      orientations. In addition, the behaviour of Haidinger's brushes when the plane of
      polarization is rotated, and their modification by optical retarders, is
      reproduced. The similarity between the simulation and the reported behaviour of
      Haidinger's brushes is consistent with the theory that the phenomenon results
      from a symmetrical distribution of dichroic pigment molecules within the macula.

PMID- 8278194
TI  - Model for co-ordination of corneal and crystalline lens power in emmetropic human
      eyes.
AB  - A mathematical model is used to investigate the co-ordination of corneal and
      crystalline lens power in emmetropia. Modelled depth changes of the anterior
      chamber, crystalline lens and vitreous chamber were based upon empirical data.
      Modelled power changes of the corneal and crystalline lens were then purely
      governed by eyeball shape. Power changes generated by the model closely agreed
      with empirical data indicating that the co-ordination of both, to maintain
      emmetropia, can be accounted for by relative axial and equatorial growth of the
      eyeball.

PMID- 8278195
TI  - Glasgow Acuity Cards: a new test for the measurement of letter acuity in
      children.
AB  - Problems with design and format of the traditional Snellen chart have led to the
      development of alternative charts for the measurement of visual acuity in adults.
      However, advances in chart design for the measurement of visual acuity in pre
      school children have not paralleled those used in adult test charts. Visual
      acuity can be measured in infants and very young children using behavioural and
      electrophysiological techniques but clinical measurement of letter acuity tends
      to commence when the child is old enough to interact and co-operate with the
      examiner. Charts which are commercially available in the UK for measuring letter
      acuity in pre-school children (3-5 years old) either use single optotypes or are
      derivatives of the Snellen format. There is a need for a test of letter acuity
      for use with this young age group which is accurate, reliable and based upon
      sound and established design principles. Glasgow Acuity Cards have been designed
      to include features that should allow change in letter acuity to be detected in
      pre-school children, especially those undergoing vision therapy training. The
      test is performed at 3 m and incorporates several design features which have been
      used previously in adult charts but are new to childrens' test charts. These
      include: linear progression of letter sizes using a log scale; letters of
      approximately equal legibility; equal number of letters per line; control of
      contour interaction; screening cards to determine initial level of acuity. The
      test is quick and easy to perform and should provide a means of detecting change
      in letter acuity, with increased confidence.

PMID- 8278196
TI  - Maximizing the dynamic range of the humphrey field analyzer for blue-on-yellow
      perimetry.
AB  - The conditions employed for blue-on-yellow perimetry (i.e. a blue stimulus filter
      and a high luminance yellow background) are in conflict with those that allow a
      maximum dynamic range. A modification is described for increasing the dynamic
      range of the Humphrey Field Analyzer (HFA) for blue-on-yellow perimetry. The
      position of the HFA stimulus bulb was lowered by reducing the length of both
      terminals. A concave mirror with a 28 mm radius of curvature was positioned
      behind the lowered stimulus bulb to give a filament image partly above and partly
      overlapping the original filament profile within the confines of the size V
      stimulus patch diameter. The modification achieved a 60% increase in the light
      output on the default 0 dB value of 10,000 apostilbs and, therefore, a useable
      dynamic range for blue-on-yellow perimetry of 2.94 log units. The effective
      increase in voltage supply to the stimulus bulb permitted a filament life of 260
      operating hours. Furthermore, the modification ensured the correct calibration of
      the instrument.

PMID- 8278197
TI  - Prescribing for presbyopes who use VDUs.
AB  - It has been widely assumed that VDU users position their paperwork closer than
      the screen to their eyes by an amount which may exceed their depth of field. The
      design and prescription of spectacles for the presbyopic VDU user must take these
      working distances into account. From theoretical considerations, the focal
      characteristics of occupational spectacles are matched to combinations of working
      distances. Measurement of these distances was carried out on a sample of 243 VDU
      users, 101 of whom were presbyopic and 53 nearing presbyopia. The results were
      analysed in terms of type of work and accommodative reserve, and compared with
      previous studies. Contrary to the views of several previous workers, it was found
      that paperwork did not tend to be positioned closer than the screen to the eyes.
      This finding was little affected by the type of VDU use or the accommodative
      reserve of the subject. Special occupational spectacle lens forms are thus not
      generally indicated for presbyopes at the VDU workstation.

PMID- 8278198
TI  - Sensitivity of off-axis performance of aspheric spectacle lenses to tilt and
      decentration.
AB  - Apparatus was modified to measure, and theoretical raytracing was used to
      predict, off-axis powers of spectacle lenses in the presence of tilt or
      decentration. In response to poor fitting in the form of tilt or decentration,
      lenses with aspheric front surfaces were found to have greater off-axis power
      errors than best-form lenses with spherical surfaces. This is attributable to the
      aspheric lenses having flatter surfaces than the spherical lenses. The errors are
      up to twice those occurring for the spherical lenses, and can be quite high, e.g.
      0.9 D astigmatism for +6D power with 10 degrees tilt in 20 degrees upgaze.
      Negative lenses are more sensitive to poor fitting than are positive lenses of
      the same power. The errors for straight ahead vision associated with tilt are
      approximately proportional to the square of the angle of tilt, and the errors for
      straight ahead vision associated with decentration are approximately proportional
      to the square of decentration. It is most important that aspheric lenses be
      correctly fitted, which means that each 2 degrees of pantascopic tilt should be
      accompanied by approximately 1 mm decentration.

PMID- 8278199
TI  - Supernumerary eyes and man's search for hyper-vision: a historical review of
      relevant representational arts.
AB  - In this paper we present examples of man's identification of superiority with
      visual hyper-efficiency. From Babylonian, Egyptian, Minoan and Biblical times,
      the eye was the symbol of the master or the inspector. Similarly, a being or
      deity that was endowed with multiple eyes--with or without multiple heads--was
      considered to be extra powerful. An example is the crest of the British College
      of Optometrists, which is surmounted by a bird with three heads and hence
      supernumerary eyes, linking it to the College's motto 'aequis oculis videre'
      denoting equal vision. We present here photographic and textual data from several
      historical periods extending from the fourth millennium BC to the sixteenth
      century AD; and from different religious sources, both Christian and non
      Christian, to support this thesis. However, these are only a few examples,
      selected from a larger on-going study of the subject.

PMID- 8278200
TI  - Can diffractive liquid crystal lenses aid presbyopes?

PMID- 8278201
TI  - Residual refraction.

PMID- 8278202
TI  - The chronic intraspinal use of opioid and local anesthetic mixtures for the
      relief of intractable pain: when all else fails!

PMID- 8278203
TI  - An empirical evaluation of multidimensional clinical outcome in chronic low back
      pain patients.
AB  - Individuals with persisting pain often present a constellation of symptoms that
      includes pain, health-related impairment and dysphoric mood. It is now widely
      accepted that comprehensive assessment must address each of these dimensions.
      Despite recognition of the value of multidimensional assessment, no empirical
      efforts have validated the construct of a multidimensional clinical outcome
      presentation based on the dimensions of pain, impairment and dysphoric mood. We
      employed cluster analytic procedures on standard measures of pain, impairment and
      depression in chronic low back pain (CLBP) patients (n = 96) attending a general
      orthopedic clinic in order to empirically characterize multidimensional clinical
      outcomes. Results indicated that 3 groups could be identified reliably: (1)
      'Chronic Pain Syndrome' (n = 25; high levels of pain, impairment and depression),
      (2) 'Positive Adaptation to Pain' (n = 24; high levels of pain with low levels of
      impairment and depression) and (3) 'Good Pain Control' (n = 47; low levels of
      pain, impairment and depression). The reliability of this cluster solution was
      supported by several tests of internal consistency. Discriminability of the
      clusters was examined across both the outcome measures themselves and several
      additional independent variables. The cluster solution was then cross-validated
      in an independent sample of pain clinic CLBP patients (n = 180) to test its
      generalizability. Finally the stability of the cluster dimensions over time was
      tested by re-assessing 36 CLBP patients 6 months after they initially were
      characterized into 1 of the 3 outcome groups on the same measures. MANOVA results
      indicated that the outcome groups were differentiated statistically across
      assessments. The multiple outcome measures did not change significantly across
      time, nor did the outcome groups change differentially across time on these
      measures. We conclude that the outcome dimensions of pain, impairment and
      depression are relatively stable phenomena that differentially describe CLBP
      patients.

PMID- 8278204
TI  - Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in
      the treatment of cancer pain: a retrospective analysis of 51 cases.
AB  - A retrospective analysis of 51 patients with cancer pain treated with a
      continuous i.t. morphine infusion through a tunnelled percutaneous catheter was
      undertaken. Because of insufficient pain relief with morphine only, 17 of these
      patients received a morphine/bupivacaine mixture. Pain relief subsequently
      improved significantly in 10 patients and a moderate improvement was present in 4
      patients. An additional analgesic effect of bupivacaine was not shown in 3
      patients with clinical signs of severe mental depression. Bupivacaine-induced
      side effects were absent below a daily dosage of 30 mg by continuous infusion. In
      all patients a gradual dose increment was observed. No serious complications,
      neurologic sequelae or meningitis occurred. It is concluded that long-term i.t.
      infusion of morphine through a tunnelled catheter can provide adequate pain
      relief in cancer patients with an acceptable risk-benefit ratio. The effects of
      long-term intrathecal co-administration of local anesthetics, especially
      bupivacaine, await further prospective evaluation.

PMID- 8278205
TI  - Comments on injectate encapsulation after long-term epidural administration.

PMID- 8278206
TI  - Comments on Coderre, T.J. et al., Pain, 52 (1993) 259-258.

PMID- 8278207
TI  - The role of the saphenous nerve in experimental sciatic nerve mononeuropathy
      produced by loose ligatures: comment.

PMID- 8278208
TI  - Comments on De Angelis and Payne, Pain, 30 (1987) 211-216.

PMID- 8278209
TI  - The language of pain management and health.

PMID- 8278210
TI  - Afferent and spinal mechanisms of joint pain.

PMID- 8278211
TI  - Vivid memory for 'everyday' pains.
AB  - A 2-part study in which memory for everyday pains was investigated is reported.
      The first part compared ratings of vivid, 'flashbulb' memories of pain and non
      pain events. Memories of pain events were rated as having been more surprising,
      having induced more negative emotional change, and having provoked greater change
      in ongoing activity than their non-pain event counterparts. In the second part of
      the study the relationship between remembering the pain event, experiencing the
      pain and re-experiencing the sensory qualities was examined. No subject reported
      sensory re-experiencing and 41% of subjects were unable to recall the sensory
      quality of the pain experience memory. Elements of pain experience (recalled
      intensity, distress and sensory quality) were differentially associated with
      components of pain event memory. Distress was associated with the reported
      frequency with which the pain event was rehearsed and with ratings of emotional
      and activity change induced by the pain event. In contrast, ratings of the
      intensity and sensory quality of the pain were associated with the reported
      vividness of the pain event memory. It is concluded that memories of painful
      events are readily retrievable and that the memory for a pain event, the sensory
      and affective qualities of pain experience and somatosensory component of pain
      are separated in their encoding and/or retrieval. The possible mechanisms whereby
      pain memories are encoded and retrieved are discussed. The clinical implications
      of the data concerning how judgements of past pain are made and the possible role
      of memory in coping are also noted.

PMID- 8278212
TI  - Site-specific modulation of morphine and swim-induced antinociception following
      thyrotropin-releasing hormone in the rat periaqueductal gray.
AB  - Central administration of thyrotropin-releasing hormone (TRH) produces a short
      lived antinociceptive response in rats, and also modulates opioid and non-opioid
      forms of antinociception. Given the presence of TRH cells, fibers and receptors
      in the periaqueductal gray (PAG), the present study examined the effects of TRH
      administered into the PAG upon antinociception following either continuous cold
      water swims (CCWS, 2 degrees C for 3.5 min) or morphine (0.1-2.5 micrograms)
      administered into the PAG on the tail-flick and jump tests, and measured changes
      in core body temperatures as well. Histological examination revealed two groups
      in which anterior PAG placements were found rostral to the dorsal raphe nucleus,
      and posterior PAG placements which were at the level of this nucleus. TRH
      produced brief (5-15 min) but significant increases in latencies and thresholds
      without altering body temperature in both anterior and posterior PAG placements.
      Whereas TRH in anterior PAG placements dose dependently (0.1-10 micrograms)
      decreased CCWS antinociception on both tests, TRH in posterior PAG placements
      significantly increased CCWS antinociception on the jump test. TRH in both
      placements reduced the magnitude of CCWS hypothermia. TRH significantly
      potentiated the magnitude and duration of both morphine antinociception and
      hyperthermia in both anterior and posterior PAG placements, and shifted
      mesencephalic morphine's antinociceptive dose-response curve significantly to the
      left. These data are discussed in terms of the role of the PAG in opioid and non
      opioid forms of stress-induced antinociception as well as morphine
      antinociception, and in terms of the roles of TRH and anterior PAG placements as
      potential candidates for a collateral inhibition model of antinociceptive
      responses.

PMID- 8278213
TI  - Effects of sympathectomy on a rat model of peripheral neuropathy.
AB  - The aim of this study was to determine the effects of sympathectomy on our
      previously developed animal model for neuropathic pain. The neuropathy was
      produced by a unilateral tight ligation of the L5 and L6 spinal nerves in 81
      rats, all of which showed a marked increase in frequency of paw lifting in
      response to innocuous mechanical stimuli and a shortened latency of paw
      withdrawal in response to noxious radiant heat stimuli on the affected limb. We
      interpreted these as behavioral signs of mechanical allodynia and heat
      hyperalgesia. Surgical sympathectomy was performed by removing the sympathetic
      chain bilaterally from the L2 to L6 levels at 1 week prior to and 1, 3 and 5
      weeks after nerve injury. In addition, the effect of sympathetic block was tested
      by systemically injecting guanethidine or phentolamine. Surgical sympathectomy
      relieved the signs of both mechanical allodynia and heat hyperalgesia. The effect
      of sympathectomy for mechanical allodynia is estimated to be almost fully
      expressed within 30 min after the operation. Sympathetic block by chemical agents
      reversibly relieved the mechanical allodynia. These data suggest that the rats in
      our model exhibit behavioral signs of neuropathic pain that are sympathetically
      maintained.

PMID- 8278214
TI  - Hyperalgesia and myoclonus in terminal cancer patients treated with continuous
      intravenous morphine.
AB  - Eight cancer patients in the terminal stages of the disease treated with high
      doses of intravenous morphine developed hyperalgesia. All cases were
      retrospectively sampled from three different hospitals in Copenhagen. Five
      patients developed universal hyperalgesia and hyperesthesia which in 2 cases were
      accompanied by myoclonus. In 3 patients a pre-existing neuralgia increased to
      excruciating intensity and in 2 of these cases myoclonus occurred simultaneously.
      Although only few clinical descriptions of the relationship between
      hyperalgesia/myoclonus and high doses of morphine are available, experimental
      support from animal studies indicates that morphine, or its metabolites, plays a
      causative role for the observed behavioural syndrome. The possible mechanisms are
      discussed and treatment proposals given suggesting the use of more efficacious
      opioids with less excitatory potency in these situations.

PMID- 8278215
TI  - Comparative local anaesthetic blocks in the diagnosis of cervical zygapophysial
      joint pain.
AB  - The utility of randomised, double-blind, controlled, comparative local
      anaesthetic blocks for the diagnosis of cervical, zygapophysial joint pain was
      studied in 47 patients with chronic neck pain following whiplash injury. Each
      patient was investigated with radiologically controlled blocks of the medial
      branches of the cervical, dorsal rami to anaesthetise the target cervical,
      zygapophysial joint. The blocks were performed using either lignocaine or
      bupivacaine, randomly allocated, and the patients' responses were assessed in a
      double-blind fashion. Any positive response was subsequently assessed by
      repeating the block with the complementary anaesthetic. Only those patients
      experiencing a longer period of pain relief from the bupivacaine were considered
      to have true-positive responses. Forty-four patients had pain relief from two
      blocks at a single level, of whom 34 had longer pain relief from bupivacaine.
      This result is unlikely to have occurred by chance (P = 0.0002). The durations of
      pain relief obtained from the anaesthetics were consistent with the known
      characteristics of these drugs with bupivacaine lasting significantly longer than
      lignocaine (P = 0.0003). A subgroup of 13 patients were identified with
      unexpected, prolonged responses to one or both of the anaesthetics. Comparative,
      diagnostic blocks are a valid technique in the identification of painful
      zygapophysial joints, and constitute an implementable alternative to normal
      saline controls.

PMID- 8278216
TI  - Characterization of Encephalitozoon hellem (Microspora) isolated from the nasal
      mucosa of a patient with AIDS.
AB  - A microsporidium of the genus Encephalitozoon was isolated into culture from the
      nasal epithelium of a patient with AIDS. It was compared with in vitro isolates
      of Encephalitozoon cuniculi and the type isolate of Encephalitozoon hellem by SDS
      PAGE and by Western blotting with murine antisera raised to E. cuniculi, E.
      hellem and the nasal isolate, monoclonal antibodies raised to E. cuniculi and
      sequential sera from the patient. All tests showed similarities between E. hellem
      and the nasal isolate but differences between these two isolates and E. cuniculi.
      Minor protein differences between E. hellem and the nasal isolate were not
      considered sufficient to separate them at the specific level. The new isolate is
      named the Wainwright isolate of E. hellem. The ultrastructure of the Wainwright
      isolate in vitro was similar to that of the parasite in vivo but there was a
      greater tendency for disruption of the parasitophorous vacuoles. The deposition
      of the electron-dense surface coat on the sporogonic stages of E. hellem, as a
      uniform layer which later thickens, is in contrast to its deposition as broad
      bands, which later join up, in E. cuniculi. This may be a useful character in
      distinguishing the species without recourse to analysis of protein profiles.

PMID- 8278217
TI  - Adhesion of parasitized red blood cells to cultured endothelial cells: a flow
      based study of isolates from Gambian children with falciparum malaria.
AB  - Adhesion of parasitized red blood cells to vascular endothelium is thought to
      play an important role in the development of the ischaemic complications
      associated with severe falciparum malaria. Using a novel, flow-based assay, we
      have investigated the adhesion of parasitized red blood cells to formalin-fixed
      human umbilical vein endothelial cells (HUVEC), for isolates obtained from 32
      Gambian subjects with mild or severe falciparum malaria. Red cells infected with
      wild strains of Plasmodium falciparum were able to adhere to HUVEC under
      physiologically relevant flow conditions, but the level of adhesion was highly
      variable, ranging from 1 to 688 adherent cells per mm2 of HUVEC. Within isolates,
      some adherent parasitized cells remained stationary, whilst other formed less
      stable interactions and rolled slowly over the cell surface. There was no
      significant difference in adhesion of parasitized cells between isolates obtained
      from mild or severe cases of malaria, although a subset of isolates did show very
      high levels of adhesion. The results suggest that there is not a simple
      relationship between the adhesion of parasitized cells to cultured endothelial
      cells (presumably via the receptor ICAM-1) and the clinical severity of the
      disease, although variation in microvascular adhesion in vivo may still be a
      determinant of ischaemic complications.

PMID- 8278218
TI  - Analysis of mixed parasite populations of Theileria sergenti using cDNA probes
      encoding a major piroplasm surface protein.
AB  - The gene for the 32 kDa surface protein (p32) of Theileria sergenti was cloned
      into lambda gt11 and its nucleotide sequence was determined. The gene encodes a
      protein of 283 amino acids as deduced from its nucleotide sequence with a 22
      residue N-terminal signal peptide. Using this cDNA as a probe we have isolated
      another two clones from a cDNA library with a CDM8 vector system derived from the
      same parasite stock. Comparison with three cDNA clones revealed differential
      polyadenylation and differences in sequences of non-coding regions. Within the
      coding regions, there were nucleotide transitions which affected the Pst I
      restriction site, and one of the transitions was also accompanied by an amino
      acid substitution (Ala to Gly). Southern blot analysis showed hybridization
      pattern changes among the parasites isolated from individual calves at different
      times after infection. From these results, we conclude that at least 3
      genetically different parasite populations may coexist, and the transition to
      predominant parasite populations might occur during persistent infections in a
      host, possibly to evade the host immune responses.

PMID- 8278219
TI  - Purification and partial characterization of malate dehydrogenase
      (decarboxylating) from Tritrichomonas foetus hydrogenosomes.
AB  - Malate dehydrogenase (decarboxylating) from Tritrichomonas foetus hydrogenosomes
      was purified close to homogeneity by a combination of differential
      centrifugation, zwitterionic detergent solubilization, Red-Sepharose
      chromatography and anion-exchange chromatography. The enzyme with apparent
      subunit size of 59 kDa and native molecular mass of 308 kDa utilized NAD+
      preferentially to NADP+ as a cofactor and required Mn2+ or Mg2+ for its activity.
      Affinity curves for malate and coenzymes were hyperbolic. Km for malate was 100
      microM and 458 microM in the presence of NAD+ and NADP+, respectively. Km for
      NAD+ and for NADP+ in the presence of malate was 18 microM and 207 microM,
      respectively. The enzyme is proposed to be a tetramer with a possible
      physiological role in the maintenance of an appropriate NAD+/NADH ratio in
      hydrogenosomes.

PMID- 8278220
TI  - Genetic structure of Trypanosoma cruzi populations from Argentina estimated from
      enzyme polymorphism.
AB  - Isolates of Trypanosoma cruzi from human patients, domestic and sylvatic animals
      and vector insects were obtained in different areas of Argentina. Electrophoretic
      patterns of enzymes from extracts of 95 isolates were analysed. On the basis of
      zymograms providing information on 10 loci, 12 zymodemes are described according
      to their genotypes. Data presented show fixed heterozygosity, absence of
      segregation of genotypes, significant departures from Hardy-Weinberg equilibrium,
      and over-represented genotypes. This evidence supports the hypothesis that sexual
      reproduction is very restricted or absent in this parasite. The proportion of
      polymorphic loci is 80%. The expected mean heterozygosity per locus (He) is 0.43,
      while the observed value (Ho) is 0.24. Differences between these values may be
      explained by accepting a basically clonal structure for T. cruzi. The data matrix
      of 12 zymodemes using 28 characters was analysed using a Wagner parsimony
      algorithm. Two equally most parsimonious unrooted trees were generated; both have
      39 steps. The results show clusters clearly separated according to the
      geographical origin of the stocks. There are some indications of some
      correlations between genetic composition of the parasite and the clinical picture
      of the infection in human patients.

PMID- 8278221
TI  - Random amplified polymorphic DNA technique for the identification of Trichinella
      species.
AB  - The random amplified polymorphic DNA (RAPD) technique was successfully used to
      produce genetic fingerprints distinguishing between Trichinella spiralis and
      Trichinella britovi. The same patterns were obtained from purified and crude DNA
      preparations of pooled and single muscle larvae. RAPD fingerprinting was applied
      to muscle larvae preserved under different conditions and recovered from
      different hosts. Larvae recovered from fresh and frozen meat and stored at -20
      degrees C for a long time or under 70% ethyl alcohol at room temperature for 30 d
      gave good and reproducible results. Single larvae recovered from a naturally
      infected wild boar and from a human biopsy gave fingerprints congruent to those
      obtained from T. britovi reference strains. The results prove that RAPD analysis
      is a quick method to distinguish between the autochthonous Trichinella species of
      Central-Southern Europe in less than 1 d after the detection of the infection. If
      necessary, the biological material can be frozen or stored under 70% ethyl
      alcohol at room temperature and sent to laboratories able to perform the RAPD
      analysis. The RAPD technique requires no prior knowledge of the molecular biology
      of the organism to be investigated and therefore appears to be a promising tool
      in parasitology for the identification of sibling species.

PMID- 8278222
TI  - Necator americanus in inbred mice: a re-evaluation of primary infection kinetics.
AB  - The course of a primary Necator americanus infection was studied in the lungs and
      small intestines of syngeneic mice. Following percutaneous infection no
      difference in initial larval establishment in the lungs was found between male
      BALB/c, NIH or B10.G mice. However, significant differences in the subsequent
      kinetics of infection were demonstrated between the BALB/c and NIH strains. Lung
      worm burdens declined more slowly in NIH mice than in BALB/c strain.
      Surprisingly, however, a greater proportion of larvae remaining in the lungs of
      BALB/c mice, 9 days p.i., were trapped than in NIH mice. Nevertheless,
      establishment in the small intestines of the BALB/c strain was consistently
      greater than in NIH mice. Host immunosuppression resulted in increased larval
      retention in the lungs of both the BALB/c and NIH strains as well as in the small
      intestines of BALB/c mice. Treatment with hydrocortisone acetate did not increase
      intestinal worm burdens in NIH mice. The data presented suggest that, in this
      complex, dynamic model system, designation of 'susceptible' and 'resistant'
      strains is inappropriate. The factors underlying the observed strain differences
      in resistance to infection are discussed.

PMID- 8278223
TI  - Ligula intestinalis (L.) (Cestoda: Pseudophyllidea): polarization of cyprinid
      leucocytes as an indicator of host- and parasite-derived chemoattractants.
AB  - Freshly isolated pronephric leucocytes from roach, Rutilus rutilus and gudgeon,
      Gobio gobio were exposed to extracts of plerocercoids of Ligula intestinalis from
      these two cyprinid fish. Addition of the extracts or an increase in incubation
      temperature from 10 to 20 degrees C induced polarization of neutrophils and L1
      granulocytes. Cells were transformed from their typical spherical shape to
      elongate forms possessing a ruffled leading edge. Extracts obtained from gudgeon
      Ligula stimulated polarization of both roach and gudgeon leucocytes at 10 and 20
      degrees C. In contrast, extracts from roach-Ligula, whilst having little effect
      at 10 degrees C, suppressed temperature-induced polarization of leucocytes at 20
      degrees C. Addition of serum to all the essays enhanced polarization and
      abolished the roach-Ligula-induced suppression. It is suggested that leucocyte
      chemoattractants are present in Ligula from roach and gudgeon and only parasites
      from the former host contain an inhibitor of polarization. In addition, host
      derived factors possibly complement, may be involved in leucocyte
      chemoattraction.

PMID- 8278224
TI  - Localization, turnover and conservation of gp15/400 in different stages of Brugia
      malayi.
AB  - The expression of a protein complex designated gp15/400, previously identified
      via extrinsic iodination of adult Brugia malayi, was examined by labelling all
      stages found in the mammalian host and immunoprecipitation with a specific
      antibody raised to a recombinant protein. In this way, gp15/400 could be detected
      in L3, L4, adult worms and microfilariae recovered from jirds and labelled with
      Bolton-Hunter reagent. Metabolic labelling indicated that gp15/400 was released
      into culture medium when adult worms were maintained in vitro, but at a rate
      slower than that of gp29, the major soluble cuticular glycoprotein. Immuno
      electron microscopy showed that the protein complex was broadly distributed in
      different tissues, although it was not detectable in the cuticle of adult worms.
      Dense labelling was observed in the matrix of the basal laminae bordering the
      hypodermis, somatic musculature and oesophagus, and lower but significant
      labelling was seen in the cells overlying these extracellular matrices.
      Hybridization of genomic DNA with a cDNA probe encoding gp15/400 indicated that
      homologous genes were present in Dirofilaria immitis and Acanthocheilonema
      viteae. The failure to detect related genes in non-filarial nematodes was
      presumed to be due to divergence beyond the practical limits of detection by
      nucleic acid probes, as antibody reagents showed that the protein cross-reacted
      immunologically with ABA-1, a major protein allergen from the body fluid of
      Ascaris.

PMID- 8278225
TI  - The effect of invertebrate hormones and potential hormone inhibitors on the third
      larval moult of the filarial nematode, Dirofilaria immitis, in vitro.
AB  - The effects of the insect hormones, ecdysone and 20-hydroxyecdysone, certain non
      steroidal ecdysteroid agonists (RH compounds) and the inhibitor, azadirachtin, on
      the timing of the 3rd-stage moult of Dirofilaria immitis were investigated. 20
      Hydroxyecdysone and RH 5849 when used at a concentration of 10(-5) M, resulted in
      a premature timing of this moult. Azadiracthin, at a similar concentration,
      prevented moulting of most of the larvae to the 4th stage. The results are
      discussed in relation to the possibility of a hormonal role for ecdysteroids and
      neuropeptide-like compounds in the control of ecdysis in filarial nematodes, that
      maybe somewhat comparable to the system which is found in insects.

PMID- 8278226
TI  - The health care reform debate: read the fine print.

PMID- 8278227
TI  - Broadening the scope of nursing practice: federal programs for children.
AB  - Various social programs are available to support the family unit when a child
      with special needs enters the health care system. Nurses are challenged to link
      families with appropriate federal programs. An understanding of selected
      legislation and the programs designed to implement those laws better enables them
      to meet that challenge.

PMID- 8278228
TI  - Participants' perceptions of a mandated training course in the identification and
      reporting of child abuse.
AB  - Professionals (N = 844) from various disciplines who had participated in a
      mandated training course in identifying and reporting child abuse were surveyed
      regarding their perceptions of the experience. The majority of the 540
      professionals who responded felt that learning objectives had been met, teaching
      methods were appropriate, the trainers were effective teachers, and the course
      content was relevant and applicable to their practice. Solicited comments and
      recommendations reflected trends in professionals' perceptions.

PMID- 8278229
TI  - Nurses as gangbusters: a response to gang violence in America.
AB  - A growing number of children in America are joining gangs. Once a youth becomes
      associated with a gang, violence may be inevitable. Previously considered only a
      criminal justice problem, violence is now regarded as a preventable public health
      problem. Health care professionals have been challenged to design effective anti
      violence strategies as part of health care reform. Nurses with knowledge about
      gangs can make a significant contribution to addressing this challenge.

PMID- 8278230
TI  - Social skills group for physically challenged school-age children.

PMID- 8278231
TI  - Dependent on technology: a child grows up hospitalized.
AB  - Growing numbers of technology assisted children are indefinitely hospitalized due
      to factors related to lack of parental and societal support. By describing the
      needs of one child, recommendations for providing comprehensive chronic inpatient
      care and strategies for securing long-term placement for the indefinitely
      hospitalized child are presented.

PMID- 8278232
TI  - The health security plan: what's in it for America's children?

PMID- 8278233
TI  - Helping nurses cope.

PMID- 8278234
TI  - Listening to the lived experience of loss.
AB  - As nurses we often underestimate the importance, significance, and therapeutic
      value of listening. When a person experiences loss and is in emotional turmoil,
      the fundamental need is to be "heard." Active listening allows us to participate
      in the inner feelings of another and to move toward an understanding of the lived
      experience of loss.

PMID- 8278235
TI  - Update: new guidelines for the treatment of infants with sickle cell disease.
      Agency for Health Care Policy and Research.
AB  - These clinical practice guidelines set forth a comprehensive program for
      identifying, diagnosing, and treating newborns and infants with sickle cell
      disease and recommend education and counseling strategies for their parents.
      Sickle cell disease comprises a group of genetic disorders characterized by the
      production of hemoglobin S, anemia, and acute and chronic tissue damage secondary
      to the blockage of blood flow by abnormally shaped red cells. Sickle cell anemia
      is the most common form of the disease, and it affects approximately 1 in 375
      African-American infants. Although in the United States sickle cell disease is
      most commonly found in persons of African ancestry, it also affects other
      populations. The panel recommends screening of all newborns for sickle cell
      disease, since targeting specific groups will miss some infected infants. Samples
      of dried blood on filter paper or liquid blood samples should be used for
      hemoglobinopathy screening. Hemoglobin electrophoresis, isoelectric focusing, and
      high performance liquid chromatography are acceptable, reliable, and accurate
      testing methods. Infants identified on initial screening must be retested to
      establish a definitive diagnosis. Affected infants must be given twice-daily oral
      penicillin beginning at 2 months of age to reduce pneumococcal, conjugated
      Haemophilus influenzae, and hepatitis B vaccines. Infants with sickle cell
      disease require the same well-child care as infants without the disease.
      Education and nondirective genetic counseling should be offered to all parents of
      infants with sickle cell disease. The guidelines stress the need for a
      comprehensive and fully integrated approach to reduce morbidity and mortality
      from sickle cell disease.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278236
TI  - Kawasaki disease: early treatment/positive results--one family's story.
AB  - Kawasaki disease is appearing with increasing frequency in the U.S. A childhood
      disease of unknown etiology, it is characterized by an acute self-limiting
      inflammation of the systemic vascular system affecting multiple organs. This
      article presents a single case of a 13-month old Caucasian male patient diagnosed
      and treated early for Kawasaki disease. Also included are the incidence of the
      disease, the clinical manifestations, a review of current literature, the
      treatment provided, and the nursing implications.

PMID- 8278237
TI  - Nurse and parent collaborative case management in a rural setting.
AB  - A collaborative parent and nurse case management model can facilitate meeting the
      variety of needs of children who have special health care problems. When families
      live in depressed social and economic conditions in rural areas, services can be
      difficult to obtain. Families can be assisted to be advocates for their children
      by a close interaction with a nurse case manager.

PMID- 8278238
TI  - Pediatric management problems. Fragile X syndrome.

PMID- 8278239
TI  - Patterns of physiologic and behavioral response of intermediate care preterm
      infants to intervention.
AB  - PURPOSE: To determine the safety of a developmental intervention for use with
      preterm infants and feasibility of a time sampling procedure. METHODOLOGY: An
      experimental design was used to test an intervention with clinically stable 33-34
      week postconceptional age infants over a 4-day period. Repeated outcome measures
      included pulse rate, oxygen saturation levels, and infant behavioral state.
      FINDINGS: The intervention resulted in significant differences in infant
      behavioral state with the experimental group achieving more alertness.
      Physiologic parameters remained within normal limits both during and after the
      intervention. CONCLUSIONS: The protocol was found to be safe for implementation
      with clinically stable preterm infants. Behavioral state findings suggest the
      potential for the intervention to promote alertness. Results suggest that changes
      in oxygen saturation and pulse rate were dependent upon changes in behavioral
      state.

PMID- 8278241
TI  - Honest admissions.

PMID- 8278240
TI  - Felbamate (Felbatol).

PMID- 8278242
TI  - Budget backflash.

PMID- 8278243
TI  - Catalogue of disaster.

PMID- 8278244
TI  - Reflection. In the hall of mirrors.

PMID- 8278245
TI  - Reflection. Growing awareness.

PMID- 8278246
TI  - Fact findings.

PMID- 8278247
TI  - Perk or poison?

PMID- 8278248
TI  - Squaring the circle.

PMID- 8278249
TI  - Systems of life. The ear and hearing. 2.

PMID- 8278250
TI  - A missing element?

PMID- 8278251
TI  - HIV nurse sues employers.

PMID- 8278252
TI  - Alexander technique.

PMID- 8278253
TI  - Equal access.

PMID- 8278254
TI  - Wound care. Centred on excellence.

PMID- 8278255
TI  - Wound care. Practice themes.

PMID- 8278256
TI  - HIV screening in pregnancy increases choice.

PMID- 8278257
TI  - Attitudes on AIDS and HIV in education.

PMID- 8278258
TI  - A new lease of life. Interview by Jane Cassidy.

PMID- 8278259
TI  - A perk too far?

PMID- 8278260
TI  - Divides and rules.

PMID- 8278261
TI  - Desperate for dollars.

PMID- 8278262
TI  - GP fundholding. Vested interests.

PMID- 8278263
TI  - GP fundholding. Mind over matter.

PMID- 8278264
TI  - Between two worlds.

PMID- 8278265
TI  - Degrees, debt and damp.

PMID- 8278266
TI  - Far from home.

PMID- 8278267
TI  - Deck the wards.

PMID- 8278268
TI  - Yuleopathy.

PMID- 8278269
TI  - Footsteps in the snow.

PMID- 8278270
TI  - I did it my way.

PMID- 8278271
TI  - The plague journals.

PMID- 8278272
TI  - Learning disabilities. Support in grief.

PMID- 8278274
TI  - Learning disabilities. Death of a friend.

PMID- 8278273
TI  - Learning disabilities. Bereavement and working with people with learning
      difficulties: when nursing goes beyond a duty of care.

PMID- 8278275
TI  - Ethics and oncology nurses.

PMID- 8278276
TI  - To know suffering.

PMID- 8278277
TI  - Patterns of mucositis and pain in patients receiving preparative chemotherapy and
      bone marrow transplantation.
AB  - The purpose of this study was to describe the incidence, onset, duration,
      severity, and other relevant characteristics of mucositis and pain in patients
      undergoing bone marrow transplant (BMT) who were receiving high-dose chemotherapy
      (cytoxan, busulfan, and etoposide) without total body irradiation. A descriptive,
      longitudinal design was used to study a sequential sample of 47 patients
      undergoing allogeneic and autologous BMT. Each day, from 9 days prior to BMT
      through 21 days after BMT, nine anatomic regions of patients' mouths were
      assessed for extent and severity of mucositis. Oral pain was measured using the
      Short-Form McGill Pain Questionnaire. Forty-two patients (89%) developed
      mucositis, which, on average, began 3 days after transplant, lasted 9.5 days, and
      resolved by 12.6 days post-transplant. Thirty-six patients (86%) reported pain
      that began, on average, 4.5 days after transplant, lasted 6.5 days, and resolved
      by 11 days post-transplant. During the initial weeks following BMT, systematic
      assessment of the oral cavity areas that are at high risk for mucositis should
      assist nurses in detecting early oral complications and in initiating specific
      interventions. Additionally, attention needs to be given to the assessment and
      management of mucositis-related oral pain. Future nursing research should be
      conducted to examine efficient clinical methods of assessing mucositis and oral
      pain and to test prophylactic and therapeutic interventions.

PMID- 8278278
TI  - Nursing care of the patient with spinal cord compression.
AB  - Spinal cord compression (SCC) is a common oncologic emergency that can profoundly
      affect the remainder of the patient's life. SCC develops when pressure is exerted
      on the spinal cord by a tumor or by a collapsed vertebral body that has been
      replaced by cancer. When the condition is diagnosed and treated early, the
      patient may maintain ambulatory status; however, when the diagnosis is made late
      and neurologic compromise has occurred already, there is minimal expectation that
      impaired functions will return. SCC is treated with dexamethasone and radiation
      therapy, and surgery occasionally is performed. Nursing care, an integral
      component in the management of this challenging condition, may be as simple as
      educating the at-risk patient about the signs and symptoms of SCC or as complex
      as meeting the many needs of the paraplegic patient. This article reviews the
      etiology and clinical presentation of SCC as well as assessment, treatment, and
      nursing care related to the condition.

PMID- 8278279
TI  - The use and meaning of touch in caring for patients with cancer.
AB  - Although touch and touching are complex phenomena that constitute an important
      aspect of nursing practice, the ways in which nurses use touch are still poorly
      understood. In this study, patterns of nurse-patient touch were examined by
      analyzing videotapes of nurses caring for patients with cancer and audiotapes of
      unstructured interviews with patients and selected nurses. Using the techniques
      of qualitative ethology, five types of touch were identified and described:
      comforting, connecting, working, orienting, and social. These types of touch are
      comparable to the two major kinds of nurse-patient touch previously identified in
      the literature: task-related touch and affective touch. However, detailed,
      qualitative descriptions of the five types of touch, the variations in associated
      verbal and nonverbal behaviors, and the associated meanings provide more
      comprehensive descriptions than previously have been available. In particular,
      the use of connecting, orienting, and social touch have not been well-recognized
      or described in the literature. Awareness of the types and meanings of touch
      affords nurses the opportunity to increase the therapeutic value of touch as a
      nursing intervention.

PMID- 8278280
TI  - Quality of life of adult long-term survivors of bone marrow transplantation: a
      qualitative analysis of narrative data.
AB  - Recently, clinicians and researchers alike have challenged the long-standing
      impression that survivors of bone marrow transplantation (BMT) experience a less
      than optimal quality of life (QOL). Despite the accumulating evidence suggesting
      that most adult survivors adjust relatively well within two to five years after
      BMT, little is known about the growing population of recipients living well
      beyond five years. This paper reports the design and qualitative components of a
      large study that used a cross-sectional, descriptive, mailed survey design. The
      aim of the study was to document systematically how 125 adult survivors of BMT (6
      18.4 years post-transplant) perceived the quality of their lives. An eight-item,
      open-ended questionnaire was used to gather information on the reestablishment of
      life after BMT, demands of recovery, coping strategies, limitations imposed by
      BMT, current health problems, QOL, and concerns for the future. Content analysis
      of the verbatim responses indicated that most long-term survivors, despite the
      persistence of lingering side effects, perceive themselves as cured and well,
      leading full and meaningful lives. Nursing therapeutics can focus on providing
      accurate and timely information about the known long-range complications of BMT.
      Further research is needed to examine the entire issue of social support
      following BMT and to identify the special care requirements of the recipients
      (5%) who reported poor physical and mental health.

PMID- 8278281
TI  - Childhood cancer: differential effects on the family members.
AB  - The purpose of this study was to describe individual, dyadic, and family
      responses to childhood cancer and related current-life stresses, self-esteem
      issues, marital satisfaction, and perceptions of family environments. A
      descriptive, correlational design was used with 20 families who had at least one
      well child and one child with cancer. Parents and children were asked to create
      drawings using a projective drawing technique called Kinetic Family Drawings
      (KFDs), then these drawings were compared with norms on the following
      quantitative measures: Schedule of Recent Experiences, Life Events Scale for
      Adolescents and Life Events Scale for Children, Culture-Free Self-Esteem
      Inventory, Dyadic Adjustment Scale, and the Family Environment Scale. Results
      supported a need to evaluate each family member's individual responses to
      childhood cancer, given the importance of the family as a social environment for
      children. Results revealed an informative and, at times, varied profile across
      instruments and family members in the areas of adjustment, life stresses, self
      esteem, marital satisfaction, and views of the family environment. For example,
      mothers reported significantly lower self-esteem than fathers. Yet, with the KFD,
      no significant differences on scores were found between family members.

PMID- 8278283
TI  - Massage provides a soothing touch.

PMID- 8278282
TI  - Sexual dysfunction following treatment for prostate cancer: nursing assessment
      and interventions.
AB  - Treatment modalities for prostate cancer include surgery, radiation therapy, and
      hormonal manipulation. Sexual dysfunction is a potential sequela of these
      treatments. Ideally, nursing interventions are begun before treatment is
      initiated. Pertinent questions enable nurses to elicit specific information
      needed to develop the patient's care plan. Sexual assessment strategies and
      interventions, such as the PLISSIT model, that can be implemented when caring for
      these patients are presented.

PMID- 8278284
TI  - Cutaneous techniques can help to control pain.

PMID- 8278285
TI  - Distraction and touch combination controls pain.

PMID- 8278286
TI  - Styrofoam cup of ice can ease injection-site pain.

PMID- 8278287
TI  - Professional associations, ethics, and society.
AB  - This article examines the role of professional associations, with particular
      reference to the Oncology Nursing Society (ONS), in relation to professional
      ethics. Also explored are the relationship between power structures and meaning
      and value structures, the relationship between the ideal of a profession and the
      reality of clinical practice, and the three functions of social ethics. Aspects
      of professional associations, ethics, and society are examined in terms of their
      reflection in the current ethical standards outlined by ONS in order to provide
      recommendations for future directions in ethics standards and oncology nursing
      practice.

PMID- 8278288
TI  - Ethical issues in oncology nursing practice: an overview of topics and
      strategies.
AB  - An understanding of common principles of biomedical ethics provide healthcare
      professions with a common language. Developing a standard approach to complex
      ethical cases in clinical situations allows professionals to involve significant
      individuals and to ensure that appropriate factors are considered. This article
      presents a case in oncology nursing practice, using a sample model for decision
      making. The case is developed to demonstrate a number of issues that arise with
      regard to symptom management, the nurse-patient relationship, informed consent,
      end-of-life decisions, and truth-telling. Ethical dilemmas arising from conflicts
      within principles and between individuals holding differing ethical perspectives
      are described. Because a true ethical dilemma goes beyond a simple "right" or
      "wrong" answer, arguments based on differing moral grounds are presented. Nursing
      responsibilities are delineated and directions are provided for furthering one's
      understanding of ethics.

PMID- 8278289
TI  - The ethical context of healthcare reform.
AB  - The purpose of this article is to provide a summary discussion of healthcare
      reform, frame it in an ethical context, and present the necessity for oncology
      nurses to consider the important ethical considerations that accompany any
      decisions for change. The resulting implications for oncology nursing are
      presented with recommendations that the issues of healthcare reform be
      incorporated into oncology nursing research, clinical practice, administration,
      and education. All components of the profession have a contribution to make as
      proposals for change move from public debate to the enactment of national
      initiatives.

PMID- 8278290
TI  - The moral context of oncology nursing.
AB  - Current work environments in health care are hierarchical social systems built
      around disease-oriented medical goals and procedures. Expansion of biomedical
      technologies and cost-containment policies have increased the ethical concerns
      and problems of nurses and other providers. Yet, nurses often are not included as
      major contributors in deliberations about solutions to these ethical problems. A
      patriarchal pattern of decision making reflects the paternalistic organization of
      patient care settings and discounts the reality that multiple providers from many
      disciplines and specialties provide patient care. To foster ethical practice as a
      shared activity, ways are needed to build work environments that foster
      interdependent practice and facilitate moral discourse among all participants.
      Actions to promote the development of work environments as moral contexts require
      systematic attention to conceptual, structural, process, and leadership issues
      that foster collaboration, open communication, and person-centered care.

PMID- 8278291
TI  - Recurrent pneumococcal meningitis. Search for occult skull fracture.
AB  - Skull fractures, particularly those affecting the base of the brain and extending
      to the sinuses and petrous pyramids, are the most common cause of recurrent
      bacterial meningitis. Detection of sinus fracture can be difficult in children.
      Thin-section computed tomographic scanning aids the diagnosis in patients with a
      remote history of head injury. Other causes of recurrent bacterial meningitis
      include congenital cranial and spinal cord defects, foci of infection, and immune
      system disorders. Streptococcus pneumoniae is often the infectious organism.
      Treatment includes surgical repair of any anatomic defects and use of appropriate
      antibiotic therapy.

PMID- 8278292
TI  - The 'Food Security Act of 1995' A scary possibility after healthcare reform.

PMID- 8278293
TI  - Lactose intolerance. Recognizing the link between diet and discomfort.
AB  - Lactose intolerance is a common disorder encountered in clinical practice.
      Evaluation involves obtaining a thorough nutritional history and recognizing
      associations between diet and gastrointestinal complaints. Lack of suspicion of
      the problem can lead to expensive and invasive diagnostic procedures, which may
      further aggravate patients' anxiety and result in iatrogenic complications. Once
      the diagnosis is confirmed, simple dietary management may resolve symptoms
      completely.

PMID- 8278294
TI  - Oncologic emergencies. Treating acute problems resulting from cancer and
      chemotherapy.
AB  - Oncologic emergencies can occur in cancer patients who have a good prognosis. In
      all of them, the challenge to the clinician is to diagnose and treat before
      irreversible complications occur. In febrile patients with neutropenia, cultures
      of body fluids should be obtained and therapy should be started immediately with
      broad-spectrum antibiotics. If spinal cord compression is suspected, either
      magnetic resonance spectroscopy or complete myelography can be done to confirm
      the diagnosis. Prompt workup in cancer patients with headaches or seizures may
      avoid neurologic consequences. For brain metastases, immediate treatment with
      dexamethasone (Decadron, Dexone, Hexadrol) is indicated. For hypercalcemia, a
      number of drugs that inhibit bone resorption, resulting in lower serum calcium
      levels, are now available. Malignant cardiac tamponade is relatively rare but
      potentially lethal; emergency pericardiocentesis often results in marked
      improvement.

PMID- 8278295
TI  - Management of depression. Current options for this highly treatable disorder.
AB  - Depression is a common disorder that leads to substantial functional impairment
      and even death if untreated. Suicide rates in persons with untreated major
      depression can be as high as 30%. However, the disorder is treatable;
      pharmacotherapy in combination with psychotherapy is effective in up to 90% of
      patients. Established diagnostic criteria enable physicians to differentiate
      major depression from other psychiatric disorders and from somatic conditions
      that may mimic depression. Current treatment options include traditional
      antidepressant medications as well as the newer serotonin-reuptake inhibitors.
      Successful treatment depends on administration of an appropriate dose for an
      adequate duration.

PMID- 8278296
TI  - Focal liver lesions. Evaluation of simple and complex cysts.
AB  - Ultrasound is often the first imaging study used to determine the nature of focal
      liver lesions. Although simple cysts often need no treatment, those large enough
      to compress or to irritate adjacent structures should be surgically unroofed and
      drained. Complex liver cysts may be caused by bacteria, amebae, or tapeworms
      (Echinococcus granulosus). Rarely, neoplasms present as cystic lesions and need
      further study for definitive diagnosis.

PMID- 8278297
TI  - Focal liver lesions. Evaluation of solid neoplasms.
AB  - A logical, stepwise approach to the diagnostic evaluation of solid focal liver
      lesions relies heavily on the fundamental clinical tools of history taking,
      physical examination, and identification of basic tumor markers. Imaging
      procedures alone or along with percutaneous, laparoscopic, or open biopsy
      techniques are then applied in order to obtain a specific diagnosis. The astute
      clinician must be concerned not only with an accurate diagnosis but also with
      therapeutic implications of the diagnosis balanced against the costs in terms of
      potential complications, survival time, resources, and patient inconvenience. A
      thorough understanding of the biologic behavior and natural history of the lesion
      helps assure a rational, cost-effective treatment strategy.

PMID- 8278298
TI  - Calcium channel antagonists. What do the second-generation agents have to offer?
AB  - Calcium channel antagonists have gained widespread acceptance for treatment of a
      variety of cardiovascular disorders. Newer drugs of the dihydropyridine class are
      especially attractive for treating hypertension and angina because of their
      increased vascular selectivity, favorable side-effect profile, and
      pharmacokinetics that allow once-daily dosing. In the future, calcium channel
      antagonists may also play a role in antiatherogenic therapy and in treatment of
      congestive heart failure and cerebrovascular disease as results of prospective
      studies become available and new agents are developed.

PMID- 8278299
TI  - What healthcare crisis?

PMID- 8278300
TI  - One possible future of medicine.

PMID- 8278301
TI  - Pediatric HIV infection and the primary care physician. Meeting unique needs.
AB  - The number of HIV-infected children and adolescents is expected to increase
      during the next decade. Most of these patients are likely to receive nearly all
      of their healthcare from primary care physicians. Management must be multifaceted
      and consist of medical care for acute illnesses, routine pediatric care that
      includes immunizations, and social service intervention.

PMID- 8278302
TI  - Opportunistic infections in AIDS patients. Current management and prevention.
AB  - The number of drugs available for treatment and prevention of opportunistic
      infections in patients who are seropositive for HIV infection is limited,
      although some agents currently being studied show promise. Pneumocystis carinii
      pneumonia, the most common opportunistic infection, can be effectively managed,
      although prophylaxis must be continued indefinitely. Because an increased
      incidence of tuberculosis is associated with HIV infection, the emergence of
      strains that are resistant to multiple drugs is of concern. Intensive therapy
      with five or six drugs may be necessary. Isoniazid (Nydrazid) is recommended for
      prophylaxis.

PMID- 8278303
TI  - Lower extremity ischemia. Interventions to preserve quality of life.
AB  - Primary care physicians play a key role in the diagnosis and management of
      peripheral vascular disease, the evaluation of which should include history
      taking, physical examination, determination of ankle-brachial index, and
      ultrasound study in the noninvasive vascular laboratory. Patients with peripheral
      vascular disease are best served by a team consisting of primary care physician,
      interventional radiologist, and vascular surgeon. Together they help the patient
      make decisions regarding noninvasive management strategies versus angiography and
      subsequent percutaneous or surgical treatment. Regular follow-up promotes the
      best long-term outlook for patients with peripheral vascular disease.

PMID- 8278304
TI  - Receptor antagonists of bradykinin: a new tool to study the cardiovascular
      effects of endogenous kinins.

PMID- 8278305
TI  - A 31P NMR spectroscopy study of Xenopus laevis heart perfused in vitro with
      creatinol-O-phosphate, phosphocreatine, adenosine triphosphate, fructose
      diphosphate and ouabain.
AB  - Xenopus laevis heart was studied by 31P NMR using a 200 MHz proton spectrometer;
      hearts were perfused, at pH 7.35 and room temperature, with normal oxygenated or
      K(+)-enriched Ringer. Solution was later added with creatinol-O-phosphate (COP),
      phosphocreatine (PCr), adenosine triphosphate (ATP), fructose-1,6-diphosphate
      (FDP) and ouabain. NMR spectra of the heart show organic phosphomono- and
      phosphodi-esters, inorganic phosphate, PCr, overlapping alpha-ATP/ADP and gamma
      ATP/beta-ADP, and beta-ATP signals. Their chemical shift positions and areas
      showed no significant changes in the course of 1.5 h perfusions with either
      solution, except in a few preparations, whether the heart was beating or
      reversibly arrested. While COP reduced the signals in beating hearts, the same
      spectra exhibited no consistent, substantial changes under PCr, ATP and FDP 1 to
      10 mM, pH 7.35 perfusion with either solution, nor when ouabain mumol was added.
      The spectra are briefly discussed in comparison with those observed in the
      perfused heart of mammals (mostly rat), and particularly with those obtained in
      the frog (Rana temporaria) heart, both by analysing the bioenergetic equilibria
      on the basis of total tissue substrate levels measured in extracts of freeze
      clamped tissue, and by evaluating cytochrome-b, flavin and pyridine nucleotide in
      vitro oxido-reduction read-outs in separate, similar experimental settings.

PMID- 8278306
TI  - Pharmacokinetics and distribution of ribonuclease and its
      monomethoxypoly(ethylene glycol) derivatives in rats.
AB  - The changes of pharmacokinetics and distribution of 3H radio-labelled
      ribonuclease (RNase) and RNase adduct with monomethoxypoly(ethylene glycol)
      (MPEG) were studied after intravenous administration in the dose of 25 mg kg-1 to
      rats. Whereas the value of total plasma clearance of RNase is close to the value
      of glomerular filtration rate, the value of that for MPEG-RNase is about three
      hundred times lower. The half-life of elimination is 79 min, 181 min and 65 h for
      RNase, MPEG and MPEG-RNase, respectively. The main elimination pathway of
      compounds under study was elimination into urine and no evident specific
      distribution in the examined organs (liver, kidney, muscle, lung, brain, spleen
      and heart) was found. The study indicates that conjugation of RNase with MPEG can
      improve its pharmacokinetic properties.

PMID- 8278307
TI  - Polymorphonuclear leukocytes activation: in vitro modulation by 6-methoxy-2
      naphthylacetic acid, the major active metabolite of nabumetone.
AB  - Reported here are the results of a study carried out in order to assess the
      possible influence of the major circulating active metabolite of nabumetone, 6
      methoxy-2-naphthylacetic acid, on some aspects of polymorphonuclear leukocytes
      activation. The action of 6-methoxy-2-naphthylacetic acid was tested on the
      following features of polymorphonuclear leukocytes activation: reactive oxygen
      species production in polymorphonuclear leukocytes stimulated with different
      agonists, reactive oxygen species production in polymorphonuclear leukocytes
      treated with pertussis toxin, NADPH-oxidase activity. The findings showed that 6
      methoxy-2-naphthylacetic acid decreased reactive oxygen species production in
      polymorphonuclear leukocytes stimulated with N-formyl-methionyl-leucyl
      phenylalanine, phorbol myristate acetate, and opsonized zymosan, but failed to
      provoke a decrease of reactive oxygen species production when the cells were
      stimulated with calcium ionophore A23187. Moreover, 6-methoxy-2-naphthylacetic
      acid did not influence the transduction of the signal following the binding of
      stimuli to membrane receptors, and NADPH-oxidase activity. Finally, our findings
      showed that 6-methoxy-2-naphthyl acetic acid had no scavenger effect on reactive
      oxygen species production.

PMID- 8278308
TI  - The clinical pharmacology of the new antiepileptic drugs.
AB  - Conventional anticonvulsants have important limitations in terms of efficacy and
      tolerability, and there is a clear need for new agents to be developed. After a
      quiescent period which lasted for more than two decades, several promising new
      compounds have undergone clinical evaluation and a few of these (vigabatrin,
      lamotrigine, oxcarbazepine, zonisamide) are now commercially available in some
      countries. Some of the new agents represent structural analogues of pre-existing
      drugs in an attempt to improve the therapeutic index of the latter (e.g.,
      oxcarbazepine), while others were rationally designed to interfere selectively
      with inhibitory (vigabatrin) or excitatory (NMDA receptor antagonists)
      neurotransmission in the brain. Many other compounds were discovered more or less
      serependitiously and their mode of action is poorly understood. The present
      article provides a concise review of the clinical pharmacology of the new
      anticonvulsants which have undergone most extensive clinical testing in patients
      with epilepsy. Topics discussed include clinical pharmacokinetics, drug
      interactions, efficacy data in selected epileptic syndromes or seizure types, and
      adverse effects profile. Although the precise role of these new agents in the
      overall management of epilepsy remains to be clearly defined, their availability
      already provides a valuable tool which can be usefully exploited to improve
      prognosis, especially in patients with the more severe forms of the disease.

PMID- 8278309
TI  - Magnetic resonance imaging of the fetus: a study of 20 cases performed without
      curarization.
AB  - Twenty patients underwent magnetic resonance imaging (MRI) at a mean gestational
      age of 32 weeks. There were 12 patients with suspected fetal brain abnormality
      and four with intrauterine growth retardation (IUGR), while the remaining four
      cases were studied for other reasons. The MRI examinations were performed on a
      0.5 Tesla machine, with surface coils. One minute acquisition time T1 sequences
      were used. All the studies were performed without fetal curarization, and only
      under maternal sedation using flunitrazepam given per os 1 h before MRI
      examination. Three examinations were incomplete because of fetal movement
      artefacts. In the remaining cases, MRI allowed the examination of fetal brain
      anatomy. In five cases, it helped to differentiate isolated hydrocephalus and
      corpus callosum agenesis. Sub-ependymal nodules were depicted in a case of fetal
      tuberous sclerosis. One suspected arachnoid cyst was proved to be an ultrasound
      artefact. Decreased fetal fat on MR images was correlated with low birth weight
      in cases of IUGR. Due to its better spatial resolution, ultrasonography was more
      accurate for the diagnosis of facial and lumbar anomalies. Fetal MRI may be
      performed without curarization. Surface coils allow the detailed analysis of
      brain parenchyma, and thus MRI is especially useful in the difficult prenatal
      diagnosis of fetal brain abnormalities.

PMID- 8278310
TI  - Cytogenetic analysis of 1375 amniotic fluid specimens from pregnancies with
      gestational age less than 14 weeks.
AB  - Our laboratory has received 1375 early amniotic fluid (EA) specimens during the
      past 5-year period for cytogenetics analysis. The gestational ages of the EA
      specimens were less than 14 weeks as estimated by ultrasound. The average volume
      of specimen received was 16 ml. Specimens were typically received in two
      collection tubes and cultured in Chang A and in supplemented MEM media using the
      in situ technique. Of the 1375 EA specimens received, 1356 were successfully
      cultured and yielded results. Abnormal results were found in 67 (4.9 per cent) of
      the cases. Nineteen specimens (1.4 per cent) failed to yield a result. The mean
      turn-around time (TAT) for all EA specimens was 8.28 days. In 1991, the average
      TAT for the EA specimens was 8.00 days compared with a TAT of 6.59 days for all
      specimens received over 14 weeks gestational age. The number of EA specimens
      received has increased from 1.5 per month in 1986 to 57 per month in 1991. In
      summary, our experience with EA specimens for cytogenetic analysis has
      demonstrated that the success rate is 98.6 per cent and that an increasing number
      of obstetricians are performing early amniocentesis as they seek to provide their
      patients with earlier results and an alternative to chorionic villus sampling.

PMID- 8278311
TI  - Prenatal cystic fibrosis carrier screening: factors in a woman's decision to
      decline testing.
AB  - Among 2207 women eligible to be screened for cystic fibrosis (CF) carrier status
      during pregnancy, 325 (15 per cent) declined to be tested. Of these, 260 (80 per
      cent) answered a questionnaire soliciting their reasons for not participating.
      The main factor was opposition to termination of pregnancy, with 43 per cent
      being against termination for any reason and another 11 per cent against
      termination of a CF fetus. Other reasons given were partner's disapproval or non
      participation (10 per cent), perceived risk of a CF child being low (7 per cent),
      the error rate of the test (6 per cent), and the generation of unacceptable
      levels of anxiety (5 per cent). Eleven women (4 per cent) said that they did not
      wish to be tested during pregnancy, but only six of these would have accepted
      screening at another time.

PMID- 8278312
TI  - Rapid detection of numerical aberrations of chromosomes 13, 18 and 21 in
      chorionic mesenchymal cells.
AB  - We have devised and evaluated a rapid screening method for the detection of
      numerical aberrations of chromosomes 13, 18 and 21 in chorionic villus cells. We
      used non-radioactive in situ hybridization (ISH) with three chromosome-specific
      probes on overnight-attached mesenchymal cells from chorionic villi. A blind
      study was performed of 47 karyotypically normal samples, one triploid sample, two
      samples trisomic for chromosome 21, and two samples from a fetus with putative
      mosaicism (46/47, +21). All samples were hybridized with the chromosome 18- and
      21-specific probes. Thirty samples were additionally hybridized with the
      chromosome 13-specific probe. The test could be completed within 3-4 days of
      sampling. In samples disomic with respect to the probed chromosomes, an average
      of 2 per cent (range 0-9 per cent) had three hybridization signals. By contrast,
      in the samples trisomic for the probed chromosome(s), 57 per cent (chromosome
      13), 51 per cent (chromosome 18), and an average of 74 per cent (55-86 per cent)
      (chromosome 21) of the nuclei exhibited three signals. In the putative mosaic
      samples, the number of nuclei with three chromosome 21-specific signals ranged
      from 41 to 69 per cent. We conclude that this technique rapidly and clearly
      distinguishes between normal and trisomic/triploid samples, and consequently may
      be of use in future prenatal diagnosis.

PMID- 8278313
TI  - Application of fluorescent in situ hybridization for 'de novo' anomalies in
      prenatal diagnosis.
AB  - Fluorescent in situ Hybridization (FISH) was carried out for three cases of
      abnormal karyotypes in prenatal studies. Two concerned de novo structural
      anomalies and the third a marker chromosome. The origin of the extra material
      could be defined in all three cases, which gives a better insight into the
      relationship between genotype and phenotype and makes more adequate genetic
      counselling possible.

PMID- 8278314
TI  - Fetal tissue involvement in the late infantile type of neuronal ceroid
      lipofuscinosis.
AB  - Prenatal diagnosis in a pregnancy at risk for late infantile neuronal ceroid
      lipofuscinosis (Batten's disease) was undertaken at 17 weeks' gestation by
      ultrastructural examination of amniotic fluid cells. The presence of curvilinear
      profiles indicated an affected fetus and the diagnosis was confirmed, after the
      pregnancy was terminated, by the finding of many typical curvilinear profiles in
      multiple tissues which included skin, amnion, umbilical vessels, blood, liver,
      and brain. Comparison between the involved cells in the amniotic fluid and fetal
      tissues suggests that these cells are probably derived from the periderm, and
      possibly also from the amnion. The prominent presence of cytosomes in the
      periderm and intermediate cells of the fetal epidermis and occasionally also in
      the endothelial cells of the dermis suggests that fetal skin may be a useful
      alternative site for assessing fetal involvement. Control specimens of the
      amniotic fluid, fetal skin, amnion, and liver showed no similar cytosomes.
      However, some control amniotic fluid samples did contain cells with large
      collections of irregular trilaminar membranes, and these could be open to
      misinterpretation. It is important that only typical curvilinear profiles are
      considered as an indication of an affected pregnancy.

PMID- 8278315
TI  - Prenatal diagnosis of gall bladder anomalies--report of 17 cases.
AB  - We describe here 17 cases of fetal gall bladder anomalies, detected as early as
      the 14th week of gestation, out of 10,016 fetal systemic examinations performed
      by us in the last 6 years (0.15 per cent). In seven cases, agenesis of the fetal
      gall bladder was detected. The diagnosis was confirmed by post-abortal
      examination in five cases and in two post-partum. In six other cases, a left
      sided gall bladder and in one case, a 'floating' gall bladder were detected at 15
      weeks' gestation. In two cases, a septated or bilobed gall bladder was
      visualized. None of these 15 cases was dyskaryotic, but in five cases, two with
      agenesis and three left-sided gall bladders were associated with other fetal
      malformations. In two other cases, the gall bladder appeared dysmorphic on
      sonographic examination and in both of them intrauterine growth retardation and
      other anomalies were detected. Trisomy 18 was diagnosed by amniocentesis in one
      of them. According to our experience, failure to visualize the fetal gall bladder
      by the 15th gestational week is diagnostic of its absence and should raise the
      differential diagnosis between gall bladder atresia, which has a good prognosis,
      and external biliary atresia, which has a poor prognosis. Further experience is
      needed to characterize the various gall bladder malformations and their
      prognosis.

PMID- 8278316
TI  - The early diagnosis of neural tube defects.
AB  - The sonographic diagnosis of fetal neural tube defects (NTDs) has been enhanced
      by the recognition of associated brain and skull anomalies. Previous reports have
      found these anomalies to be accurate in predicting spina bifida after 16 weeks'
      gestation, and an inverse correlation was suggested between the presence of these
      sonographic markers and gestational age. Therefore, we assumed that early second
      trimester sonography would be at least as accurate as that performed after 16
      weeks' gestation. To examine this hypothesis, we looked for the presence of these
      cranial sonographic markers suggestive of open NTDs in 8011 low-risk cases, using
      transvaginal sonography (TVS), between the 12th and 17th week of gestation
      (menstrual age). Fetal NTDs were identified in ten cases (1.25/1000). The NTDs
      were cervico-cranial in three, lumbo-sacral in six, and thoracal in one of the
      ten cases. None of the seven cases examined was dyskaryotic. Cerebellar
      dysmorphism, 'banana' sign, cerebellar absence, and hypoplasia were detected in
      all the low NTDs, usually before the detection of the spinal lesion. All the
      sonographically diagnosed malformations were confirmed by post-abortal
      examination except in one case, where the patient decided to continue the
      pregnancy and refused follow-up. We therefore conclude that transvaginal
      sonographic examination of the fetal skull before the 17th week of gestation is
      an accurate method for the detection of low NTDs.

PMID- 8278317
TI  - Polymerase chain reaction analysis of the cystic fibrosis delta F508 mutation in
      human blastomeres following oocyte injection of a single sperm from a carrier.
AB  - The efficiency of the polymerase chain reaction (PCR) in detecting the cystic
      fibrosis (CF) delta F508 mutation (which is the most common mutation of CF) was
      assessed in single human blastomeres. Twenty-one human immature oocytes (germinal
      vesicle-stage oocytes) that had been donated for research were matured in vitro
      and a single spermatozoon from a carrier of the CF delta F508 mutation was
      injected into the ooplasm. Fourteen embryos were obtained after intracytoplasmic
      sperm injection (ICSI). PCR analysis was carried out on 70 single blastomeres
      isolated from these 14 embryos. The results showed that the efficiency of DNA
      amplification by PCR in single nucleate blastomeres was 94 per cent (59/63).
      There were no false-positive results since none of the blank samples or the
      blastomeres without a nucleus showed an amplified signal. We found that nine
      embryos were homozygous for the unaffected genotype and that four embryos were
      heterozygous since they contained both the unaffected and the delta F508
      genotype. In a four-cell embryo, we observed the homozygous unaffected genotype
      in one blastomere and a heterozygous delta F508/unaffected genotype in the other
      three blastomeres.

PMID- 8278318
TI  - Prenatal diagnosis of DHPR deficiency by direct detection of mutation.
AB  - Prenatal diagnosis was requested by a family carrying a 3 base-pair insertion in
      the dihydropteridine reductase (DHPR) coding region. A chorionic villus sample
      was obtained and fetal DNA was isolated directly from this. Diagnosis was
      performed by a polymerase chain reaction (PCR)-based technique, with a simple
      electrophoretic assay for the insertion. The fetus was found to be heterozygous
      for the insertion. This is the first time that prenatal diagnosis of DHPR
      deficiency has been performed by direct detection of the mutation.

PMID- 8278319
TI  - A triploid fetus with a diploid placenta: proposal of a mechanism.

PMID- 8278320
TI  - [Pulsatile secretion of insulin].

PMID- 8278321
TI  - [Cytoplasm antibodies of polynuclear neutrophils in Wegener's granulomatosis and
      systemic vasculitis].
AB  - In retrospective and prospective studies the sera of 442 patients recruited from
      an Internal Medicine department were examined by acetone indirect
      immunofluorescence and immunoblot in search of anti-neutrophil cytoplasm
      antibodies (ANCA). Twenty-three patients had Wegener's granulomatosis, and 419
      had various control diseases including connective tissue diseases, vasculitis and
      granulomatosis. The sera from 100 healthy blood donors were used as controls.
      Among the 23 patients with generalized (n = 15) or localized (n = 8) Wegener's
      granulomatosis (active in 21/23), the indirect immunofluorescence test was
      positive in 92 percent of those with the generalized form and in 62 percent of
      those with the localized form. Nine of the 13 sera examined by immunoblot (69
      percent) were positive (31 +/- 57 kDa bands). On the other hand, the sera from 38
      (6.9 percent) patients with control diseases were positive at immunofluorescence:
      vasculitis (14 cases, 50 percent), connective tissue diseases (4 cases, 14.3
      percent) and miscellaneous diseases including 3 neoplasms (10 cases, 35.7
      percent). Only 6 of these 28 sera showed a 1/100th titer of ANCA. The sera of all
      healthy controls were negative. The sensitivity of ANCA for Wegener's
      granulomatosis at all stages was 72.2 percent, and its specificity 94.4 percent.
      This study confirms the value of ANCA as third diagnostic criterion of Wegener's
      granulomatosis, after the clinical and histological criteria.

PMID- 8278322
TI  - [Emergency treatment of calculi of the lower ureter].
AB  - Two-hundred patients were hospitalized as an emergency for lower ureteral
      calculi. Eighty-two of these patients has a less than 6 mm wide calculus which
      was evacuated by medical treatment; 5 had stagnant infected urine which was
      drained by endoprosthesis; 113 had an obstructive calculus which resisted medical
      treatment and was treated by ureteroscopy: the stone could be removed by means of
      a basket catheter in 58 cases, but this method failed in the other cases and the
      calculus has to be broken by laser. There were 6 failures due to the nature of
      the stone (monohydrated oxalate) in 3 cases and to technical laser problems in 3
      cases. The success rate of ureteroscopy (basket catheter or laser) was 95 percent
      in patients whose pain had persisted under medical treatment.

PMID- 8278323
TI  - [Rupture of aneurysm of the splenic artery during the first three months of
      pregnancy].
AB  - A rare but dramatic case of haemoperitoneum of non-gynaecological origin which
      occurred during pregnancy is reported. Obstetrical causes of shock having been
      excluded, laparotomy made it possible to discover an aneurysm of the splenic
      artery and treat it by resection-ligation and splenectomy. In such cases, the
      uterus is spared before the 6th month of pregnancy, and beyond that data
      caesarean section is mandatory. The pathogenesis of such arterial ruptures during
      pregnancy is unknown. The abrupt collapse accounts for the high maternal and
      foetal mortality. Prevention can only be achieved by surgical treatment of all
      uncomplicated aneurysm of the splenic artery in young women.

PMID- 8278324
TI  - [Common variable hypogammaglobulinemia. A rare cause of chronic diarrhea. A
      case].
AB  - In patients with chronic diarrhoea investigations exceptionally reveal a common
      variable hypogammaglobulinaemia. A 42-year old man presenting with chronic
      bronchitis and asymptomatic post-hepatitis B cirrhosis was hospitalized for
      evaluation of a chronic diarrhoea accompanied by altered general condition.
      Investigations detected global hypogammaglobulinaemia, diffuse lymphoid
      hyperplasia of the small bowel, and lambliasis. Treatment with gammaglobulins and
      antibiotics resulted in disappearance of symptoms. This was a rare disease due to
      a primary disorder where global hypogammaglobulinaemia was associated with a
      normal number of circulating B-cells. Prognosis was cautious in view of the risk
      of malignant proliferation.

PMID- 8278325
TI  - [Left ventricular post-infarction remodeling. Natural history and therapeutic
      implications].
AB  - Post-infarction remodeling consists of changes in the size and shape of the left
      ventricular cavity taking place after myocardial necrosis. These changes in
      ventricular geometry involve the infarcted area as well as the myocardium
      situated at a distance from the infarct. The main factors of remodeling are the
      location, transmurality and extent of the necrosis, the current ventricular load,
      the patency of the artery responsible for the infarction, the distribution of
      coronary lesions and the absence of functional collateral circulation. Remodeling
      begins early and progresses during the weeks and months which follow the acute
      episode. Dilatation of the left ventricle is of poor prognosis, the principal
      complication being the development of congestive heart failure. Concerning
      treatment, the arterial recanalization obtained in the first hours is usually
      accompanied by a lesser ventricular dilatation. In case of extensive infarct with
      alteration of the global ventricular function, vasodilators, and notably
      angiotensin-converting enzyme inhibitors, attenuate the remodeling process and
      improve the mid- or long-term prognosis.

PMID- 8278326
TI  - [Fecal platelet-activating factor (PAF). A marker of digestive inflammatory
      disorders].
AB  - PAF (platelet-activating factor) is a phospholipid compound with harmful
      inflammatory effects on the gastrointestinal tract of animals. Recent studies
      have reported the presence of PAF in the stools of patients with inflammatory gut
      diseases such as Crohn's disease, ulcerative colitis, pouchitis and bacterial
      diarrhoea. PAF might be implicated in the occurrence and perpetuation of the
      digestive tract inflammatory symptoms observed in these diseases. The beneficial
      use of PAF antagonists in inflammatory diseases of the gastrointestinal tract
      deserves to be assessed.

PMID- 8278327
TI  - [Sarcoidosis secondary to bilateral breast paraffinoma].

PMID- 8278328
TI  - [Transmission of Plasmodium falciparum following an accidental sting].

PMID- 8278329
TI  - [Autoimmune hypothyroidism of mixte, central and peripheral origin in an elderly
      woman].

PMID- 8278330
TI  - [Efficacy of atovaquone in resistant toxoplasmosis in AIDS].

PMID- 8278331
TI  - [Congenital dyserythropoiesis. Value of isotopic exploration with iron 59 and
      chromium 51 marked red cells].

PMID- 8278332
TI  - [Horton disease revealed by cortical blindness].

PMID- 8278333
TI  - Fasciola hepatica: tegumental surface changes in adult and juvenile flukes
      following treatment in vitro with the sulphoxide metabolite of triclabendazole
      (Fasinex).
AB  - The effects of the novel benzimidazole, triclabendazole (Fasinex, Ciba-Geigy), in
      its active sulphoxide metabolite form (TCBZ-SX), on the tegumental surface of
      Fasciola hepatica has been examined in vitro. The tegument of adult flukes
      incubated in TCBZ-SX (50 micrograms/ml) appeared swollen and blebbed after only 6
      h. In addition, progressive spine loss at the oral cone was evident following 12
      h treatment. After 24 h, the tegumental syncytium and spines had completely
      sloughed away, leaving an exposed basal lamina and empty spine sockets. Juvenile
      flukes (3 weeks old) also demonstrated tegumental alterations after treatment
      with TCBZ-SX (20 micrograms/ml). The syncytium became extremely roughened and
      corrugated on both dorsal and ventral surfaces after only 3 h. Following 6- and 9
      h incubations, there were many deep furrows, which were especially pronounced on
      the ventral surface, and by 18 h, the juvenile tegument was severely disrupted,
      especially on the ventral surface. In all cases, the effects were more marked
      than in the previous incubation periods. The results confirm the potent activity
      of triclabendazole against F. hepatica and suggest that the tegument of adult and
      juvenile flukes may be a target organ for this important fasciolicide.

PMID- 8278334
TI  - Studies on Echinococcus granulosus using the scanning electron microscope. I.
      Preparations of the parasite for infection of the final host.
AB  - The development of the protoscoleces of Echinococcus granulosus was studied after
      chemical stimulation, which mimics that offered by the final host. This
      stimulation resulted in some morphological changes in the parasite and to its
      evagination. These changes prepare the parasite to infect the intestine of its
      final host. The external morphology of the protoscolex body and of the germinal
      layer of the cyst and brood capsule were studied using the scanning electron
      microscope (SEM). Findings were related to other studies using the transmission
      electron microscope (TEM). The morphology of the flame cell is described and four
      cases of teratogenesis are reported.

PMID- 8278335
TI  - Studies on Echinococcus granulosus using the scanning electron microscope. II.
      The hooks.
AB  - The morphology of the hooks of Echinococcus granulosus at the protoscolex level
      was studied by means of scanning electron microscopy. Hooks were uncovered in
      situ and also freed from the rostellum so as to study them in detail. There were
      two types of hooks: those of the upper row, which were larger and had a
      projecting, rounded stout guard, and those of the lower row, which were smaller
      and had a flattened guard. These and other differences in the morphology of the
      two types of hooks were studied and related to the differences in their function.

PMID- 8278336
TI  - Comparable seropositivity for ascariasis and toxocariasis in tropical slum
      children.
AB  - The seropositivities for infection by Ascaris lumbricoides and Toxocara canis
      were determined in children (1-15 years old) of a slum area of Caracas,
      Venezuela, and the levels that indicate the presence of active infection were
      defined. In children aged from 1 to 3 years, approximately 10% were positive for
      either parasite, and this figure increased to about 30% in 4- to 6-year-olds. For
      toxocariasis, the percentage of positivity remained at this level up to the age
      of 15 years. Whilst the positivity in children 10-15 years of age was comparable
      for Ascaris and Toxocara, a peak of positivity (50%) was found for Ascaris at 7-9
      years of age. These results indicate that for these urban slum children,
      infection by Toxocara is essentially as common as that by Ascaris and, thus, that
      toxocariasis represents a potential public health problem in the tropical
      environment that is largely overlooked.

PMID- 8278337
TI  - Intracellular lectin-binding sites in symbiont-bearing Crithidia species.
AB  - Crithidia oncopelti, C. deanei, and C. desouzai are flagellates of the
      Trypanosomatidae family that present bacterium-like endosymbionts in their
      cytoplasm. Direct and indirect lectin-gold labeling techniques were used at the
      electron microscopic level in Lowicryl K4M-embedded cells to demonstrate the
      presence of intracellular lectin-binding sites. We used the lectins Ulex
      europaeus I, Griffonia simplicifolia II, Ricinus communis I, Arachis hypogaea, G.
      simplicifolia I, Wistaria floribunda, Limulus polyphemus, and Canavalia
      ensiformis, which recognize alpha-L-fucose, alpha- and beta-N-acetylglucosamine,
      beta-galactose and beta-N-acetylgalactosamine, beta-galactose, alpha-galactose,
      beta-N-acetylgalactosamine, sialic acid and alpha-D-mannose, and alpha-D-glucose
      residues, respectively. The nucleus was the cellular structure most frequently
      labeled by the lectins. The Golgi complex was seldom labeled, whereas the
      endoplasmic reticulum and the flagellar pocket presented a large number of
      binding sites. Symbionts had their two unit membranes weakly labeled by the
      different lectins but displayed no labeling of the space between the membranes.

PMID- 8278338
TI  - Treatment of fish parasites. 10. Effects of a new triazine derivative, HOE 092 V,
      on Monogenea: a light and transmission electron microscopy study.
AB  - For chemotherapy of fish parasitized by monogeneans, a novel triazine derivative,
      2-[3,5-alpha-dichloro-4-(4-methyl-sulfonylphenoxy)-phenyl]-1-methy l- hexahydro
      1,2,4-triazine-3,5-dion (HOE 092 V), was tested in vivo against the gill- and
      skin-parasitizing species Dactylogyrus extensus, D. vastator, and Gyrodactylus
      arcuatus. Naturally infected fish were incubated in aerated, separate tanks at 22
      degrees C for 1, 2, 3, and 4 h in water containing 0, 1, 5, 10, or 15 micrograms
      HOE 092 V/ml, whereas Pseudodactylogyrus bini was tested in vitro at 10
      micrograms HOE 092 V/ml for 2.25 h. As seen by means of transmission electron
      microscopy, in vivo treatment against D. extensus caused vacuolization and lysis
      of the parasite's tegument at a dose as low as 1 micrograms/ml over a 3-h
      exposure period. Higher doses, such as 5 and 10 micrograms/ml over the same
      exposure period, produced lesions in the circular and longitudinal musculature of
      D. extensus and differing degrees of damage to the ciliary cells of
      protonephridia and immature vitelline cells. There was 100% mortality in D.
      vastator when incubation was done with 10 micrograms HOE 092 V/ml for 4 h (G.
      arcuatus; 5 micrograms/ml for 4 h; 10 micrograms/ml for 1 h) and in P. bini after
      2.25 h in vitro exposure. In all species tested, the anterior portion and the
      opisthaptor region were most sensitive to the drug action.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8278339
TI  - Effects of pyrantel pamoate on adult and preadult Toxocara canis worms: an
      electron microscope and autoradiography study.
AB  - Adult as well as preadult Toxocara canis isolated from the intestine of a beagle
      were incubated for 2, 4, and 14 h in medium containing either different
      concentrations of pyrantel pamoate (23.6, 236, and 2360 micrograms/ml medium) or
      tritiated pyrantel pamoate (2.36 micrograms/ml medium). These incubations were
      performed to study the effects of pyrantel pamoate on the morphology of the
      parasitic nematodes and to obtain information concerning the mode of uptake, the
      distribution, and the total amount of pyrantel pamoate ingested by T. canis. The
      results of the ultrastructure studies indicate that the intestine, hypodermis,
      and muscle cells are the organs that are predominantly affected by the drug.
      Additionally, it turned out that the duration of the treatment, i.e., the
      incubation time, was more important in determining the efficacy of pyrantel
      pamoate against T. canis than was the concentration itself. Autoradiography
      studies revealed that the adult worms ingest the drug orally, whereas preadults
      absorb pyrantel pamoate mainly through the whole body surface. Finally,
      measurements of the total amount of pyrantel pamoate taken up by T. canis
      indicated that adult worms can limit or even reduce the ingestion of pyrantel for
      more than 4 h, but then ingest large amounts of the drug. Preadult worms,
      however, absorb the drug more or less continuously during the first 14 h through
      the cuticula, albeit in lower concentrations than the adults. The different
      experiments elucidate differences in the uptake of pyrantel pamoate as well as in
      the total amount of drug ingested or absorbed by adult or preadult worms, leading
      to the assumption that repeated treatment with lower concentrations will be more
      effective than high concentrations given only once.

PMID- 8278340
TI  - Accessibility and distribution of intraerythrocytic antigens of Plasmodium
      infected erythrocytes following mild glutaraldehyde fixation and detergent
      extraction.
AB  - Malarial antigens on the surface of infected erythrocytes have been described by
      many investigators. However, few of these antigens have been unambiguously
      demonstrated to be exposed on the surface of erythrocytes. This study
      demonstrates that mild glutaraldehyde fixation results in the cytoplasmic face of
      the host membrane becoming accessible to antibody under conditions that normally
      do not expose the cytoplasmic face of uninfected erythrocytes. These results
      indicate that caution should be used in interpreting data on the membrane
      disposition of malarial antigens. Detergent extraction of the glutaraldehyde
      fixed erythrocytes results in an increased permeabilization such that malarial
      antigens on the parasite surface and within the cytoplasm of the infected
      erythrocyte are accessible to antibody. The accessibility of these antigens was
      demonstrated by both immunofluorescence and two-color flow cytometry. The
      antigens within the host cytoplasm were not diffuse but associated with patchy
      aggregates. Analysis of the antigens associated with the cytoplasmic aggregates
      by immunoelectron microscopy indicated that they were not associated with
      membrane-bound compartments. The fixation and permeabilization protocol described
      herein will have useful applications for the characterization and analysis of
      malarial antigens.

PMID- 8278341
TI  - Characterization of an immunodominant Giardia lamblia protein antigen related to
      alpha giardin.
AB  - The trophozoites of Giardia lamblia possess several protein antigens, predominant
      among them a protein of approximately 32,000 Da. In the present study, we used
      monospecific antibodies that recognize this protein to demonstrate its presence
      on a variety of G. lamblia isolates from human and animal sources. Immune
      electron microscopy was used to localize 32-kDa antigen on the trophozoite
      membrane and disk. Immunofluorescent assays employing monospecific antibodies
      confirmed the presence of 32-kDa antigen on the membrane and disk and its absence
      on flagella or nuclei. The N-terminal 17 amino acids of the 32-kDa antigen are
      identical to alpha-1-giardin, a protein component of microribbons on the ventral
      disk. These results suggest that the 32-kDa immunodominant trophozoite antigen is
      alpha-1-giardin.

PMID- 8278342
TI  - Migration of sporozoites and merogony of Eimeria coecicola in gut-associated
      lymphoid tissue.
AB  - The invasive phase of Eimeria coecicola was studied during the first 80 h
      postinoculation (p.i.). Using a method that synchronized the life cycle,
      sporozoites were observed in the duodenum and the jejunum until 32 h p.i. They
      were seen first in the villous epithelial cells or in host cells resembling
      intraepithelial lymphocytes (IEL). Later they were observed in IEL in the lamina
      propria. After 48 h p.i., no coccidian stage was identifiable in the mucosa of
      the small intestine but sporozoites appeared in the lymphoid cells of lymphatic
      follicles of the gut-associated lymphoid tissue (vermiform appendix, sacculus
      rotundus, and Peyer's patches). The first merogony was observed 64 h p.i. in
      these lymphoid cells and in membranous epithelial cells (M-cells) but was never
      seen in the epithelium itself. Morphologically there were two types of meronts,
      depending on the host cell type, but in both cases the merozoites contained a
      refractile body and resembled sporozoites. The first meronts of the second
      generation were observed 80 h p.i. in the villous epithelial cells of the domes
      of the follicles of the gut-associated lymphoid tissue, where the further
      development of this Eimeria takes place. This pattern of invasion strongly
      suggests that sporozoites take an exclusively extraintestinal route to reach the
      target cells. Moreover, to our knowledge this is the first description of an
      eimerian merogony that does not take place in epithelial cells.

PMID- 8278343
TI  - Infectivity and sporogony of Caryospora-type oocysts of Isospora rivolta obtained
      by heating.
AB  - The infectivity and sporogony of Caryospora-type oocysts of Isospora rivolta
      obtained by heat treatment were examined. Fresh unsporulated oocysts of I.
      rivolta were heated at 50 degrees C for 5 min, then poured into a cold 2%
      potassium dichromate solution and incubated at 25 degrees C. To observe the stage
      of sporulation, 100 oocysts were examined at 2-h intervals after incubation. The
      earliest sporulated oocysts were observed at 14 h and the sporulation time was 22
      h, similar to that of nontreated oocysts. To determine the infectivity, only
      Caryospora-type oocysts were collected after sporulation and inoculated orally
      into cats and mice. The mice were killed at 7 days after inoculation, and their
      mesenteric lymph nodes and spleens were fed to other cats. All of these cats shed
      oocysts. The newly discharged oocysts developed into the Isospora type after
      sporulation. These results suggest that the Caryospora-type oocysts transformed
      only morphologically after heat treatment and were as infective as the nontreated
      oocysts to host animals.

PMID- 8278344
TI  - Doramectin, a new avermectin highly efficacious against gastrointestinal
      nematodes and lungworms of cattle and pigs: two studies carried out under field
      conditions in Germany.
AB  - Two field studies were carried out to confirm the efficacy of doramectin in
      cattle and pigs in Europe. A total of 40 cattle harbouring naturally acquired
      infections of gastrointestinal nematodes, including Ostertagia spp.,
      Oesophagostomum spp., Cooperia spp., Haemonchus spp., Nematodirus spp. and
      Trichuris spp., were allocated to a treated or a control group (20
      animals/group), and 100 harbouring naturally acquired infections of
      gastrointestinal nematodes and lungworms, including Oesophagostomum spp.,
      Metastrongylus spp., Ascaris suum and Trichuris suis, were allocated to either a
      treated (60 pigs) or a control (40 pigs) group. Animals in the treated groups
      received an injection of doramectin at 200 micrograms/kg (1 ml/50 kg) for cattle
      or 300 micrograms/kg (1 ml/33 kg) for swine. Animals in the control groups
      received saline at 1 ml/50 kg for cattle or 1 ml/33 kg for swine. The cattle were
      injected by the subcutaneous route in the lateral mid-line of the neck and the
      pigs were injected intramuscularly in the neck. Faecal egg counts were determined
      for all animals on days--7, 0, 7, 14 and 21 of the studies, where day 0 was the
      day of treatment. The mean daily weight gain of doramectin-treated animals was
      significantly higher than that of the control animals over the 21 days of the
      studies (P < 0.0007 for cattle and P = 0.0001 for swine). At 21 days after
      treatment, the mean faecal egg counts of the doramectin-treated animals were
      significantly lower than those of the control animals and were reduced by 100% as
      compared with pretreatment levels. No adverse reaction to treatment was observed
      in any animal during either study.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278345
TI  - Pathogenicity of Entamoeba histolytica isolates from Shanghai, China.

PMID- 8278346
TI  - Ultrastructure of rosette formation by Plasmodium coatneyi-infected erythrocytes
      of rhesus.

PMID- 8278347
TI  - Axenic culture of Blastocystis hominis in Iscove's modified Dulbecco's medium.

PMID- 8278348
TI  - Incomplete development of larval Echinococcus multilocularis (Cestoda: Taeniidae)
      in spontaneously infected wild boars.

PMID- 8278349
TI  - Oligosaccharide signals: from plant defense to parasite offense.

PMID- 8278350
TI  - The isolated catalytic domain of NIFA, a bacterial enhancer-binding protein,
      activates transcription in vitro: activation is inhibited by NIFL.
AB  - The NIFA protein of Klebsiella pneumoniae is required for transcription of all
      nif (nitrogen fixation) operons except the regulatory nifLA operon itself. NIFA
      activates transcription of nif operons by the alternative holoenzyme form of RNA
      polymerase, sigma 54-holoenzyme, in a nucleoside triphosphate (NTP)-dependent
      manner. NIFL antagonizes the action of NIFA in the presence of molecular oxygen
      or combined nitrogen. The NIFA protein of K. pneumoniae is composed of three
      domains: an N-terminal domain with unclear function, a central catalytic domain,
      and a C-terminal DNA-binding domain. We report that the isolated central domain
      of NIFA activates transcription in vitro and that this activation requires NTP
      with a hydrolyzable beta-gamma bond, as does activation by intact NIFA.
      Transcriptional activation by the isolated central domain has the heat lability
      characteristic of intact NIFA and is inhibited by NIFL. The central domain has an
      NTPase activity that is also heat-labile but is not inhibited by NIFL. Taken
      together, these results imply that NIFL interferes with contact between NIFA and
      sigma 54-holoenzyme.

PMID- 8278351
TI  - Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese
      diabetic mice.
AB  - Anti-CD3 monoclonal antibodies suppress immune responses by transient T-cell
      depletion and antigenic modulation of the CD3/T-cell receptor complex. Anti-CD3
      treatment of adult nonobese diabetic (NOD) mice, a spontaneous model of T-cell
      mediated autoimmune insulin-dependent diabetes mellitus, significantly inhibits
      the autoimmune process. Short-term low-dose anti-CD3 treatment (5 micrograms/day
      i.v. for 5 consecutive days) prevented the occurrence of an accelerated form of
      the disease induced by cyclophosphamide. More unexpectedly, when applied to adult
      NOD females within 7 days of the onset of full-blown diabetes, the same anti-CD3
      regimen induced a complete remission of overt disease (i.e., a return to
      permanent normoglycemia) in 64-80% of mice. This remission was durable (> 4
      months) and was not associated with the disappearance of insulitis (mononuclear
      cell infiltration of the islets). The immunosuppression was apparently specific
      for beta-cell-associated antigens, since mice showing anti-CD3-induced remission
      rejected histoincompatible skin grafts normally, whereas they did not destroy
      syngeneic islet grafts, unlike control untreated overtly diabetic NOD females.
      These results open major therapeutic perspectives. They strongly suggest that
      self-tolerance can be restored in adult mice once autoimmunity is fully
      established and confirm that this effect can be obtained by transient targeting
      of the CD3/T-cell receptor without massive T-cell debulking.

PMID- 8278352
TI  - Strain-specific and tissue-specific expression of mouse mast cell secretory
      granule proteases.
AB  - As assessed by RNA blot analyses with gene-specific probes, we report that the
      perivascular connective tissue mast cells (CTMCs) in the ear and skin of BALB/cJ
      mice contain abundant levels of the mouse mast cell protease (mMCP) 7 transcript,
      in addition to those protease transcripts present in their serosal mast cells
      (SMCs). High levels of the mMCP-7 transcript also were detected in the ears of
      WBB6F1/J(-)+/+, WCB6F1/J(-)+/+, WB/ReJ(-)+/+, and WC/ReJ(-)+/+ mice. However, the
      ears of these four strains and the SMCs from the WCB6F1/J(-)+/+ strain but not
      the BALB/cJ strain also contained high steady-state levels of the mMCP-2
      transcript. The mMCP-2, mMCP-4, mMCP-5, mMCP-6, and mMCP-7 transcripts were not
      detected in the ears of mast-cell-deficient WBB6F1/J-W/Wv and WCB6F1/J-Sl/Sld
      mice, indicating that mast cells were the source of these protease transcripts in
      the +/+ animals. When immunohistochemical analyses of serial sections of ear and
      skin from WBB6F1/J(-)+/+ mice were performed with anti-mMCP-2 IgG and anti-mMCP-5
      IgG, the perivascular CTMCs in these tissues were found to express both mMCP-2
      and mMCP-5 in their granules. The prominent expression of mMCP-7 in constitutive
      perivascular CTMCs indicates that this mast cell has an extended protease
      phenotype relative to the SMCs of the same strains. Further, the perivascular
      CTMCs and SMCs of the +/+ strains differ from those in BALB/cJ mice in their
      prominent expression of mMCP-2.

PMID- 8278353
TI  - Expression cloning of a rat liver Na(+)-independent organic anion transporter.
AB  - Using expression cloning in Xenopus laevis oocytes, we have isolated a cDNA
      encoding a rat liver organic anion-transporting polypeptide (oatp). The cloned
      oatp mediated Na(+)-independent uptake of sulfobromophthalein (BSP) which was Cl(
      )-dependent in the presence of bovine serum albumin (BSA) at low BSP
      concentrations (e.g., 2 microM). Addition of increasing amounts of BSA had no
      effects on the maximal velocity of initial BSP uptake, but it increased the Km
      value from 1.5 microM (no BSA) to 24 microM (BSA/BSP molar ratio, 3.7) and 35
      microM (BSA/BSP ratio, 18.4). In addition to BSP, the cloned oatp also mediated
      Na(+)-independent uptake of conjugated (taurocholate) and unconjugated (cholate)
      bile acids. Sequence analysis of the cDNA revealed an open reading frame of 2010
      nucleotides coding for a protein of 670 amino acids (calculated molecular mass,
      74 kDa) with four possible N-linked glycosylation sites and 10 putative
      transmembrane domains. Translation experiments in vitro indicated that the
      transporter was indeed glycosylated and that its polypeptide backbone had an
      apparent molecular mass of 59 kDa. Northern blot analysis with the cloned probe
      revealed crossreactivity with several mRNA species from rat liver, kidney, brain,
      lung, skeletal muscle, and proximal colon as well as from liver tissues of mouse
      and rabbit, but not of skate (Raja erinacea) and human.

PMID- 8278354
TI  - Sialokinin I and II: vasodilatory tachykinins from the yellow fever mosquito
      Aedes aegypti.
AB  - The saliva of the mosquito Aedes aegypti has previously been reported to contain
      a 1400-Da peptide with pharmacological properties typical of a tachykinin. In the
      present study this vasodilator has been purified to homogeneity and found to
      consist of two peptides: sialokinin I, with the sequence Asn-Thr-Gly-Asp-Lys-Phe
      Tyr-Gly-Leu-Met-NH2, and sialokinin II, identical to sialokinin I except for an
      Asp in position 1. These peptides are present in amounts of 0.62 and 0.16 pmol
      (711 and 178 ng), respectively, per salivary gland pair. When assayed on the
      guinea pig ileum, both peptides are as active as the mammalian tachykinin
      substance P, with K0.5 values of 5.07, 6.58, and 4.94 nM for sialokinin I,
      sialokinin II, and substance P, respectively.

PMID- 8278355
TI  - Detergent-enabled transport of proteins and nucleic acids through hydrophobic
      solvents.
AB  - It is demonstrated that proteins and nucleic acids can be transported through
      hydrophobic organic solvents (liquid membranes) via nonspecific complex formation
      with detergents, whereas no macromolecule transport is observed without the
      latter. A protein (or a nucleic acid) first interacts with an oppositely charged
      detergent due to hydrophobic ion pairing in the aqueous feed phase. The resultant
      hydrophobic complex readily partitions into an organic solvent and then into the
      aqueous receiver phase, where it dissociates. Experiments with (i) different
      detergent/protein molar ratios, (ii) a range of unrelated organic solvents as
      liquid membranes, and (iii) homologous detergents with hydrophobic tails of
      varying lengths indicate that the protein flux through the membrane directly
      correlates with the partitioning of the protein-detergent complexes from the
      aqueous feed into the organic phase. Very little protein transport was detected
      at detergent concentrations above the critical micelle concentration, suggesting
      that individual detergent molecules, rather than micelles, play the key role. The
      rate of the detergent-enabled protein transport is not a function of the protein
      molecular weight, provided that enough detergent molecules bind to make the
      complex sufficiently hydrophobic; e.g., bovine serum albumin can be transported
      faster than insulin, which is less than 1/10th of its size.

PMID- 8278356
TI  - Role of adrenal renin in the regulation of adrenal steroidogenesis by
      corticotropin.
AB  - The major regulator of mineralocorticoid production in the adrenal is angiotensin
      II produced by the action of renal renin. The discovery that the rodent adrenal
      also synthesizes renin and angiotensinogen suggests there is autocrine regulation
      of mineralocorticoid synthesis. The transgenic rat [TGR(mREN2)27] expresses the
      Ren-2d gene predominantly in the adrenal. Despite suppressed kidney and plasma
      renin, these animals develop fulminant hypertension between 5 and 15 weeks of
      age. Corticosteroid concentrations are significantly elevated during hypertension
      development. We assessed steroidogenesis in TGR(mREN2)27 rats by analyzing the
      expression of the mRNAs for three steroidogenic enzymes: P450scc, the rate
      limiting step of steroidogenesis; P450c11 beta, which converts
      deoxycorticosterone to corticosterone in the zona fasciculata/reticularis; and
      P450c11AS, which converts deoxycorticosterone to aldosterone in the zona
      glomerulosa. P450c11AS mRNA, but neither P450c11 beta nor P450scc mRNA, was
      overexpressed in the adrenal gland of TGR(mREN2)27 rats. In situ hybridization
      with specific probes for P450c11 beta and P450c11AS mRNA localized the former
      exclusively to the zona fasciculata and the latter to the zona glomerulosa. In
      TGR(mREN2)27 rats, the size of the adrenal and number of P450c11AS-expressing
      zona glomerulosa cells were about twice those of a normal Sprague-Dawley rat.
      Both animals respond to corticotropin similarly; corticotropin had no effect on
      the expression of P450scc and P45011 beta mRNAs, rendered P450c11AS mRNA
      undetectable, and simultaneously altered the morphology of the adrenal cortex,
      resulting in a lack of zona glomerulosa-like cells. Thus, the local renin
      angiotensin system has a major effect on the basal expression of P450c11AS mRNA,
      but little effect on the corticotropin-regulated expression of P450scc, P450c11
      beta, and P450c11AS mRNAs.

PMID- 8278357
TI  - Deletion of the E4 region of the genome produces adenovirus DNA concatemers.
AB  - Two mutants containing large deletions in the E4 region of the adenovirus genome
      H5dl366 (91.9-98.3 map units) and H2dl808 (93.0-97.1 map units) were used to
      investigate the role of E4 genes in adenovirus DNA synthesis. Infection of KB
      human epidermoid carcinoma cells with either mutant resulted in production of
      large concatemers of viral DNA. Only monomer viral genome forms were produced,
      however, when mutants infected W162 cells, a monkey kidney cell line transformed
      with and expressing the E4 genes. Diffusible E4 gene products, therefore,
      complement the E4 mutant phenotype. The viral DNA concatemers produced in dl366-
      and dl808-infected KB cells did not have any specific orientation of monomer
      joining: the junctions consisted of head-to-head, head-to-tail, and tail-to-tail
      joints. The junctions were covalently linked molecules, but molecules were not
      precisely joined, and restriction enzyme maps revealed a heterogeneous size
      distribution of junction fragments. A series of mutants that disrupted single E4
      open reading frames (ORFs) was also studied: none showed phenotypes similar to
      that of dl366 or dl808. Mutants containing defects in both ORF3 and ORF6,
      however, manifested the concatemer phenotype, indicating redundancy in genes
      preventing concatemer formation. These data suggest that the E4 ORFs 3 and 6
      express functions critical for regulation of viral DNA replication and that
      concatemer intermediates may exist during adenovirus DNA synthesis.

PMID- 8278358
TI  - Stimulation of transcytosis of the polymeric immunoglobulin receptor by dimeric
      IgA.
AB  - The polymeric immunoglobulin receptor (pIgR) is transcytosed from the basolateral
      to the apical surface of polarized epithelial cells. We have previously shown
      that phosphorylation of Ser-664 in the cytoplasmic domain of the pIgR is a signal
      for its transcytosis. We now report that binding of a physiological ligand,
      dimeric IgA, to pIgR stimulates pIgR transcytosis. This stimulation occurs in
      both the presence or absence of Ser-664 phosphorylation. We have used three
      methods to measure transcytosis of the pIgR. (i) The pIgR was biosynthetically
      labeled and its cleavage to secretory component after transcytosis was measured.
      (ii) The pIgR was labeled with biotin at the basolateral surface. After
      transcytosis, release of the biotin-labeled secretory component into the apical
      medium was measured. (iii) Transcytosis of a ligand bound to the pIgR was
      measured. All three methods indicated that dimeric IgA stimulates transcytosis of
      the pIgR.

PMID- 8278359
TI  - Spermidine deficiency increases +1 ribosomal frameshifting efficiency and
      inhibits Ty1 retrotransposition in Saccharomyces cerevisiae.
AB  - Polyamines have been implicated in nucleic acid-related functions and in protein
      biosynthesis. RNA sequences that specifically direct ribosomes to shift reading
      frame in the -1 and +1 directions may be used to probe the mechanisms controlling
      translational fidelity. We examined the effects of spermidine on translational
      fidelity by an in vivo assay in which changes in beta-galactosidase activity are
      dependent on yeast retrovirus Ty +1 and yeast double-stranded RNA virus L-A -1
      ribosomal frameshifting signals. In spe2 delta mutants of Saccharomyces
      cerevisiae, which cannot make spermidine as a result of a deletion in the SPE2
      gene, there is a marked elevation in +1 but no change in -1 ribosomal
      frameshifting. The increase in +1 ribosomal frameshifting efficiency is
      accompanied by a striking decrease in Ty1 retrotransposition.

PMID- 8278360
TI  - The frequency of gene targeting in yeast depends on the number of target copies.
AB  - We have compared the efficiency of transformation by linear DNA fragments in
      yeast strains carrying different numbers of homologous targets for recombination.
      In strains carrying dispersed copies of a target and in strains carrying tandem
      arrays, the frequency of transformation is proportional to the number of targets.
      This result is in contrast to previous studies of transformation in mammalian
      cells, where targeted integration was insensitive to the number of targets. We
      conclude that, in yeast, the search for a homologous partner is a rate-limiting
      step in the successful recombination of linearized DNA fragments. Furthermore,
      the fact that we obtain the same results with both dispersed and clustered
      targets argues against models of homology searching in which DNA becomes
      nonspecifically associated with a chromosome and then slides along the DNA until
      homology is encountered.

PMID- 8278361
TI  - Homeostatic regulation of hepatocyte nuclear transcription factor 1 expression in
      cultured hepatoma cells.
AB  - Serum colloid osmotic pressure is believed to control the hepatic output of
      plasma proteins, including albumin. The present study was aimed at identifying
      the molecular basis for feedback control of albumin gene expression in highly
      differentiated hepatoma cells. The steady-state level of albumin mRNA and the
      activity of a 282-bp albumin promoter-chloramphenicol acetyltransferase reporter
      gene in cells incubated in the presence of increasing amounts of serum albumin or
      dextran were significantly and selectively decreased. When nuclear extracts from
      cells exposed to 5% (wt/vol) serum albumin were tested in a gel-retardation assay
      with six oligonucleotide probes containing DNA elements of the albumin promoter,
      only the element B-retarded band, which contains the nucleotide recognition
      sequence for hepatocyte nuclear transcription factor 1 alpha (HNF-1 alpha), was
      consistently decreased as compared to nuclear extract from cells not exposed to
      serum albumin. Moreover, the activity of a reporter gene with a basal TATA
      promoter driven by multiple HNF-1 alpha recognition elements was selectively
      inhibited in cells incubated in the presence of 5% serum albumin. A reduction of
      HNF-1 alpha mRNA appears to be responsible for this response to a change in the
      level of macromolecules in the incubation medium. These results indicate that
      activity of a dominant liver transcription factor, HNF-1 alpha, controlling the
      transcription of several liver-specific genes, is modulated by a fluctuation in
      the level of oncotically active macromolecules.

PMID- 8278362
TI  - Nitrophenyl-EGTA, a photolabile chelator that selectively binds Ca2+ with high
      affinity and releases it rapidly upon photolysis.
AB  - The synthesis and properties of a caged calcium are described. The compound is an
      ortho-nitrophenyl derivative of EGTA. It is synthesized in 10 steps and with 24%
      overall yield. The photosensitive chelator, nitrophenyl-EGTA, has a Kd value for
      Ca2+ of 80 nM and for Mg2+ of 9 mM. Upon exposure to UV radiation (approximately
      350 nm), the chelator is cleaved, yielding iminodiacetic acid photoproducts with
      low Ca affinity (Kd = 1 mM). The quantum yield of photolysis of nitrophenyl-EGTA
      in the presence of Ca2+ is 0.23 and in the absence of Ca2+ is 0.20. In
      experiments with chemically skinned skeletal muscle fibers, a fully relaxed fiber
      equilibrated with nitrophenyl-EGTA-Ca2+ complex, in the presence of 1 mM free
      Mg2+, maximally contracted after a single flash from a frequency-doubled ruby
      laser (347 nm). Half-maximal tension was achieved in 18 ms at 15 degrees C.
      Nitrophenyl-EGTA provides a tool for the investigation of the mechanism of Ca(2+)
      dependent physiological processes, since under conditions of normal intracellular
      Ca2+ and Mg2+ concentrations, only Ca2+ is bound by the photolabile chelator and
      on illumination released rapidly and in high photochemical yield.

PMID- 8278363
TI  - A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the
      dTAFII110 component of the Drosophila TFIID complex and mediates transcriptional
      activation.
AB  - Activation of transcription by the promoter-specific factor Sp1 requires
      coactivators that are tightly associated with the TATA-box-binding protein (TBP)
      in the TFIID complex. Recent work has shown that the two glutamine-rich
      activation domains of Sp1, A and B, can interact with at least one component of
      this complex, the TBP-associated factor dTAFII110. Here we report the mapping of
      a region of Sp1 with alternating glutamine and hydrophobic residues which is
      required for the interaction with dTAFII110 and is important for mediating
      transcriptional activation. Substitution of bulky hydrophobic residues within
      this region decreased both interaction with dTAFII110 and transcriptional
      activation in Drosophila cells. In contrast, mutation of glutamine residues in
      this region had no effect. Thus, the strength of the Sp1-TAF interaction
      correlates with the potency of Sp1 as a transcriptional activator, indicating
      that this activator-TAF interaction is an important part of the mechanism of
      transcriptional activation. Sequence comparison of three activation domains shown
      to bind dTAFII110 suggests that different activators that utilize dTAFII110 as a
      coactivator may share common sequence features that we have determined to be
      important for the Sp1-dTAFII110 interaction.

PMID- 8278364
TI  - Structure of the autoinducer required for expression of Pseudomonas aeruginosa
      virulence genes.
AB  - In Pseudomonas aeruginosa the LasR protein is required for activation of lasB and
      several other virulence genes. A diffusible signal molecule, the P. aeruginosa
      autoinducer (PAI), produced by the bacterial cell and released into the growth
      medium, is required for activity of LasR. By cloning a lasB::lacZ fusion and a
      lasR gene under control of the lac promoter in Escherichia coli, we have
      developed a quantitative bioassay for PAI. We have used this assay to follow the
      purification of PAI from cell-free culture supernatant fluids in which P.
      aeruginosa or E. coli containing the P. aeruginosa gene required for autoinducer
      synthesis, lasI, had been grown. Chemical analyses indicated the purified
      material was 3-oxo-N-(tetrahydro-2-oxo-3-furanyl)dodecanamide. To confirm this
      assignment, the compound was synthesized and the synthetic compound was shown to
      have chemical and biological properties identical to those of PAI purified from
      culture supernatant fluids. The elucidation of the PAI structure suggests
      therapeutic approaches toward control of P. aeruginosa infections.

PMID- 8278365
TI  - Enhanced force generation by smooth muscle myosin in vitro.
AB  - To determine whether the apparent enhanced force-generating capabilities of
      smooth muscle relative to skeletal muscle are inherent to the myosin cross
      bridge, the isometric steady-state force produced by myosin in the in vitro
      motility assay was measured. In this assay, myosin adhered to a glass surface
      pulls on an actin filament that is attached to an ultracompliant (50-200 nm/pN)
      glass microneedle. The number of myosin cross-bridge heads able to interact with
      a length of actin filament was estimated by measuring the density of
      biochemically active myosin adhered to the surface; with this estimate, the
      average force per cross-bridge head of smooth and skeletal muscle myosins is 0.6
      pN and 0.2 pN, respectively. Surprisingly, smooth muscle myosin generates
      approximately three times greater average force per cross-bridge head than does
      skeletal muscle myosin.

PMID- 8278366
TI  - Experimental specification of cell sorting, tissue spreading, and specific
      spatial patterning by quantitative differences in cadherin expression.
AB  - The sorting-out of embryonic cells from a cell mixture and the selective
      spreading of one cell population over the surface of another have been attributed
      to various causes. These include differentials in chemotaxis, in cellular
      adhesiveness, in cell surface contractility, in speed of cell movement, and in
      the timing of postulated changes in cellular adhesive and motile properties. One
      of us earlier predicted on mathematical grounds that two motile cell types
      differing only in the level of expression of a single cell adhesion system should
      not only segregate from one another but also arrange themselves with the less
      cohesive cells enveloping a core of the more cohesive ones. To test these
      predictions, we combined two populations of L cells transfected with P-cadherin
      cDNA and expressing this homophilic adhesion molecule in substantially differing
      amounts. When the two cell populations were intermixed, they segregated to
      approach a sphere-within-a-sphere configuration, the cell population expressing
      more P-cadherin forming islands which fused to become an internal "medulla." When
      the two cell populations were first formed into separate aggregates which were
      subsequently allowed to fuse, the cell population expressing more P-cadherin was
      enveloped by its partner, which formed an external "cortex." These observations
      confirm the early prediction and support the conclusion that both morphogenetic
      movements and the specific anatomical configurations to which they lead can be
      determined by particular sets of intercellular adhesive intensities, regardless
      of how these are generated and in the absence of differentials in other
      parameters.

PMID- 8278367
TI  - Tissue distribution of glycine N-methyltransferase, a major folate-binding
      protein of liver.
AB  - Glycine N-methyltransferase (GNMT; S-adenosyl-L-methionine:glycine N
      methyltransferase, EC 2.1.1.20) is a major protein in rat liver that binds 5
      methyltetrahydrofolate polyglutamate in vivo. This enzyme is believed to function
      in the regulation of the availability of S-adenosylmethionine, the primary donor
      of methyl groups in the body. The distribution of GNMT in a variety of rat
      tissues was examined immunohistochemically. In liver, GNMT was most abundant in
      the periportal region, whereas in kidney it was seen primarily in the proximal
      convoluted tubules. In pancreas, GNMT was abundant, principally in the exocrine
      tissue. GNMT was present in the striated duct cells of the submaxillary gland. In
      the jejunum, GNMT was found in the epithelial cells of the villi. Close
      examination of the liver indicated GNMT in the nucleus; this site was confirmed
      by purification of the nuclei and measurement of enzyme activity. The location of
      GNMT in the liver and kidney suggests that this enzyme plays a role in
      gluconeogenesis, while its presence in the exocrine cells suggests it may also be
      a factor in secretion.

PMID- 8278368
TI  - Prolonged and effective blockade of tumor necrosis factor activity through
      adenovirus-mediated gene transfer.
AB  - A chimeric protein capable of binding and neutralizing tumor necrosis factor
      (TNF) and lymphotoxin was expressed in mice transduced with a replication
      incompetent adenoviral vector into which a TNF inhibitor gene had been
      engineered. Within 3 days following the injection of 10(9) infectious particles,
      the TNF inhibitor concentration exceeded 1 mg/ml of plasma; this level of
      expression was maintained for at least 4 weeks, and detectable TNF inhibitory
      activity was measured 6 weeks after injection of the recombinant virus.
      Introduction of the artificial gene produced a phenotypic effect comparable to
      homozygous deletion of the 55-kDa TNF receptor, in that animals were rendered
      highly susceptible to infection by Listeria monocytogenes, whereas control
      animals receiving a replication-incompetent virus coding for beta-galactosidase
      were capable of resisting Listeria challenge. Adenovirus-mediated transfer of a
      gene encoding a TNF inhibitor offers a practical means of imposing effective,
      long-term blockade of TNF activity in vivo for investigational and therapeutic
      purposes.

PMID- 8278369
TI  - Extending nondirectional heterogeneity tests to evaluate simply ordered
      alternative hypotheses.
AB  - Biologists frequently use nondirectional heterogeneity tests when comparing three
      or more populations because a suitable directional test is unavailable or is not
      practical to implement. Here we describe a test, the ordered heterogeneity test,
      that permits testing against simply ordered alternative hypotheses in the context
      of almost any nondirectional test. The test has a wide range of parametric and
      nonparametric applications. Graphs are developed for calculating exact P values.

PMID- 8278370
TI  - Crystal structure of peanut lectin, a protein with an unusual quaternary
      structure.
AB  - The x-ray crystal structure of the tetrameric T-antigen-binding lectin from
      peanut, M(r) 110,000, has been determined by using the multiple isomorphous
      replacement method and refined to an R value of 0.218 for 22,155 reflections
      within the 10- to 2.95-A resolution range. Each subunit has essentially the same
      characteristic tertiary fold that is found in other legume lectins. The
      structure, however, exhibits an unusual quaternary arrangement of subunits.
      Unlike other well-characterized tetrameric proteins with identical subunits,
      peanut lectin has neither 222 (D2) nor fourfold (C4) symmetry. A
      noncrystallographic twofold axis relates two halves of the molecule. The two
      monomers in each half are related by a local twofold axis. The mutual disposition
      of the axes is such that they do not lead to a closed point group. Furthermore,
      the structure of peanut lectin demonstrates that differences in subunit
      arrangement in legume lectins could be due to factors intrinsic to the protein
      molecule and, contrary to earlier suggestions, are not necessarily caused by
      interactions involving covalently linked sugar. The structure provides a useful
      framework for exploring the structural basis and the functional implications of
      the variability in the subunit arrangement in legume lectins despite all of them
      having nearly the same subunit structure, and also for investigating the general
      problem of "open" quaternary assembly in oligomeric proteins.

PMID- 8278371
TI  - Nicotinic acid hydroxylase from Clostridium barkeri: electron paramagnetic
      resonance studies show that selenium is coordinated with molybdenum in the
      catalytically active selenium-dependent enzyme.
AB  - Nicotinic acid hydroxylase from Clostridium barkeri contains selenium in an
      unidentified form that is dissociated as a low molecular weight compound upon
      denaturation of the enzyme. Other cofactors of this enzyme are molybdopterin,
      FAD, and iron-sulfur clusters. In the current study, we show that the enzyme, as
      isolated, exhibits a stable Mo(V) electron paramagnetic resonance (EPR) signal
      ("resting" signal) and that this signal is correlated with the selenium content
      and nicotinate hydroxylase activity of the enzyme. Substitution of 77Se for
      normal selenium isotope abundance results in splitting of the Mo(V) EPR signal of
      the native protein without affecting the iron signals of the FeS clusters. The
      Mo(V) EPR signal and nicotinic acid hydroxylase activity of enzyme isolated from
      cells grown in selenium-deficient medium are barely detectable. In contrast, the
      EPR signals of the FeS clusters, the electronic absorption spectrum, the NADPH
      oxidase activity, and the chromatographic behavior are changed little and are
      typical of active selenium-containing enzyme. An EPR signal indicative of the
      presence of molybdenum in the selenium-deficient enzyme also is exhibited. From
      these results, we conclude that a dissociable selenium moiety is coordinated
      directly with molybdenum in the molybdopterin cofactor and, moreover, this
      selenium is essential for nicotinic acid hydroxylase activity.

PMID- 8278372
TI  - Oxidative metal release from metallothionein via zinc-thiol/disulfide
      interchange.
AB  - Mammalian metallothionein has been postulated to play a pivotal role in cellular
      zinc distribution. All seven of its metal atoms are bound with high thermodynamic
      stability in two clusters buried deeply in the molecule. If the protein is to
      function in metal delivery, there must be a biological mechanism to facilitate
      metal release. One means to achieve this would be a labilization of the clusters
      by interaction of metallothionein with an appropriate cellular ligand. To search
      for such a mediator, we have designed a rapid radiochromatographic method that
      can detect changes in the zinc content of 65Zn-labeled metallothionein in
      response to other biomolecules. Using this methodology, we have established that
      rabbit liver metallothionein 2 interacts with glutathione disulfide with
      concomitant release of zinc. Under conditions of pseudo-first-order kinetics, the
      monophasic reaction depends linearly on the concentration of glutathione
      disulfide in the range from 5 to 30 mM with a second-order rate constant k = 4.9
      x 10(-3)s-1.M-1 (pH 8.6; 25 degrees C). Apparently, zinc release does not involve
      direct access of glutathione disulfide to the inner coordination sphere of the
      metals. Rather it appears that the solvent-accessible zinc-bound thiolates in two
      clefts of each domain of metallothionein [Robbins, A. H., McRee, D. E.,
      Williamson, M., Collett, S. A., Xuong, N. H., Furey, W. F., Wang, B. C. & Stout,
      C. D. (1991) J. Mol. Biol. 221, 1269-1293] participate in a thiol/disulfide
      interchange with glutathione disulfide. This rate-limiting initial S-thiolation,
      which occurs with indistinguishable rates in both clusters, then causes the
      clusters to collapse and release their zinc. Such a mechanism of metal release
      would link the control of the metal content of metallothionein to the cellular
      glutathione redox status and raises important questions about the physiological
      implications of this observation with regard to a role of glutathione in zinc
      metabolism and in making zinc available for other biomolecules.

PMID- 8278373
TI  - A membrane form of brain L-glutamate decarboxylase: identification, isolation,
      and its relation to insulin-dependent mellitus.
AB  - A membrane form of L-glutamate decarboxylase (GAD) was identified and purified to
      apparent homogeneity from hog brain. The purified GAD was established as an
      integral membrane protein by phase-partitioning assay, charge-shift
      electrophoresis, and chromatography on a hydrophobic interaction column. This
      membrane GAD has a native molecular mass of 96 +/- 5 kDa and is a homodimer of 48
      +/- 3-kDa subunits. Immunoprecipitation and immunoblotting tests revealed the
      presence of antibodies against this membrane GAD in sera from patients with
      insulin-dependent diabetes mellitus. Since this form of GAD appears to be an
      integral membrane protein and is presumed to have extracellular domains exposed,
      it seems reasonable to suggest that membrane GAD is more likely than soluble GAD
      to be involved in the pathogenesis of insulin-dependent diabetes and related
      autoimmune disorders such as stiff-man syndrome.

PMID- 8278374
TI  - The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology,
      ontogenesis, and molecular cloning.
AB  - Water balance in the lung is controlled via active Na+ and Cl- transport.
      Electrophysiological measurements on lung epithelial cells demonstrated the
      presence of a Na+ channel that is inhibited by amiloride (K0.5 = 90 nM) and some
      of its derivatives such as phenamil (K0.5 = 19 nM) and benzamil (K0.5 = 14 nM)
      but not by ethylisopropylamiloride. An amiloride-sensitive Na+ channel of 4 pS
      was recorded from outside-out patches excised from the apical membrane. This
      channel is highly selective for Na+ (PNa+/PK+ > or = to 10). Isolation of a human
      lung cDNA led to the primary structure of the lung Na+ channel. The corresponding
      protein is 669 residues long and has two large hydrophobic domains. An amiloride
      sensitive Na(+)-selective current apparently identical to the one observed in
      lung epithelial cells was recorded after expression of the cloned channel in
      oocytes. The level of the mRNA for the Na+ channel was highly increased from
      fetal to newborn and adult stages. This observation indicates that the increased
      Na+ reabsorption that occurs at birth as a necessary event to pass to an air
      breathing environment is probably associated with control of transcription of
      this Na+ channel. The human gene for the lung Na+ channel was mapped on
      chromosome 12p13.

PMID- 8278375
TI  - Histidine-367 of the human common beta chain of the receptor is critical for high
      affinity binding of human granulocyte-macrophage colony-stimulating factor.
AB  - High-affinity receptors for granulocyte-macrophage colony-stimulating factor (GM
      CSF), interleukin 3, and interleukin 5 consist of ligand-specific alpha chains
      (low-affinity subunits) and a common beta chain (beta c) that converts each
      complex to a high-affinity form. Although beta c alone has no detectable cytokine
      binding activity, amino acid substitutions for Glu-21 of human GM-CSF
      significantly reduce high-affinity but not low-affinity binding, implying that
      beta c interacts directly with GM-CSF during formation of the high-affinity
      receptor but only in the presence of the alpha chain. A potential GM-CSF-binding
      determinant was identified in the second hemopoietin domain of beta c, and the
      role of individual residues within this region was investigated by determining
      the ability of mutated beta c chains to confer high-affinity binding when
      coexpressed with the alpha subunit of the GM-CSF receptor in COS cells.
      Substitutions involving Met-363, Arg-364, Tyr-365, and Glu-366 did not affect
      high-affinity binding. However, substitution of His-367 by lysine or glutamine
      abolished high-affinity binding, suggesting that this residue may form an
      important part of the high-affinity GM-CSF-binding determinant. Consistent with
      the loss of high-affinity binding, higher concentrations of human GM-CSF were
      required to stimulate proliferation of CTLL-2 cell lines transfected with cDNAs
      for GM-CSF receptor alpha chain and His-367 beta c mutant than those expressing
      GM-CSF receptor alpha subunit and beta c wild type.

PMID- 8278376
TI  - Saturation mutagenesis of a polyadenylation signal reveals a hexanucleotide
      element essential for mRNA 3' end formation in Saccharomyces cerevisiae.
AB  - The cis-acting signal sequences required for mRNA 3' end formation are highly
      conserved and well characterized in higher eukaryotes. However, the situation in
      the yeast Saccharomyces cerevisiae is still unclear. Several sequences have been
      proposed which share only limited similarities. One difficulty in identifying
      yeast polyadenylylation signals might be the presence of redundant signal
      sequences in the 3' region of yeast genes. To circumvent this problem we have
      analyzed the heterologous 3' region from cauliflower mosaic virus which contains
      a yeast polyadenylylation signal. We have performed a saturation mutagenesis of
      the key element TAG-TATGTA, which is a condensed version of the polyadenylylation
      signal TAG ... TATGTA ... (TTT) which had previously been proposed. Each of the
      nine nucleotides was replaced by the three other possible nucleotides and all
      resulting 1-bp mutants were tested for their capacity to specify mRNA 3' end
      formation in yeast cells. The first three nucleotides of this condensed sequence
      are not required, but mutagenesis of the other six nucleotides had distinct
      effects on mRNA 3' end formation. All mutants that were significantly functional
      had the sequence TAYRTA, and the sequence TATATA had the best capacity for mRNA
      3' end formation. The two thymidine residues at the first and fifth positions are
      the most essential nucleotides in this sequence. Our results suggest that a
      degenerate hexanucleotide is essential for mRNA 3' end formation in yeast. This
      is reminiscent of the conserved polyadenylylation signal in higher eukaryotes,
      AATAAA.

PMID- 8278377
TI  - Isolation and characterization of major histocompatibility complex class IIB
      genes from the nurse shark.
AB  - The major histocompatibility complex (MHC) contains a set of linked genes which
      encode cell surface proteins involved in the binding of small peptide antigens
      for their subsequent recognition by T lymphocytes. MHC proteins share structural
      features and the presence and location of polymorphic residues which play a role
      in the binding of antigens. In order to compare the structure of these molecules
      and gain insights into their evolution, we have isolated two MHC class IIB genes
      from the nurse shark, Ginglymostoma cirratum. Two clones, most probably alleles,
      encode proteins which differ by 13 amino acids located in the putative antigen
      binding cleft. The protein structure and the location of polymorphic residues are
      similar to their mammalian counterparts. Although these genes appear to encode a
      typical MHC protein, no T-cell-mediated responses have been demonstrated in
      cartilaginous fish. The nurse shark represents the most phylogenetically
      primitive organism in which both class IIA [Kasahara, M., Vazquez, M., Sato, K.,
      McKinney, E.C. & Flajnik, M.F. (1992) Proc. Natl. Acad. Sci USA 89, 6688-6692]
      and class IIB genes, presumably encoding the alpha/beta heterodimer, have been
      isolated.

PMID- 8278378
TI  - Direct measurement of forces between self-assembled proteins: temperature
      dependent exponential forces between collagen triple helices.
AB  - We report direct measurements of force vs. separation between self-assembled
      proteins. These forces are observed between collagen triple helices in native and
      reconstituted fibers. They are a combination of a short-range repulsion, which
      varies exponentially over at least five decay lengths, and an inferred, longer
      ranged attraction responsible for spontaneous assembly. From 5 degrees C to 35
      degrees C the relative contribution of the attraction to the net force increases
      with temperature. These forces are strikingly similar to the "hydration" forces
      measured between several other linear macromolecules (DNA, polysaccharides) and
      between lipid bilayer membranes. The decay length of the repulsive force agrees
      well with a theoretical estimate based on axial periodicity of the triple helix,
      suggesting another connection between molecular architecture and protein-protein
      interaction.

PMID- 8278379
TI  - Autoregulation of I kappa B alpha activity.
AB  - Transcription factor NF-kappa B regulates the expression of a plethora of genes.
      The activity of NF-kappa B proteins is regulated by I kappa B proteins. We report
      that induction of I kappa B alpha, a member of the I kappa B family of proteins,
      is preceded by activation of NF-kappa B complex. The promoter of the I kappa B
      alpha gene contains a kappa B site that is directly involved in its induction by
      the NF-kappa B complex. Degradation of I kappa B alpha protein precedes
      activation of NF-kappa B DNA binding activity, whereas newly synthesized I kappa
      B alpha protein inhibits NF-kappa B activity. If the degradation of I kappa B
      alpha is prevented, the induction of DNA binding activity of NF-kappa B complex
      is severely curtailed. These data suggest the existence of an autoregulatory loop
      whereby I kappa B alpha regulates the activity of transcription factor NF-kappa
      B, which in turn regulates the I kappa B alpha activity.

PMID- 8278380
TI  - Variable thermal emission and chlorophyll fluorescence in photosystem II
      particles.
AB  - In photosynthetic systems, the absorbed light energy is used to generate electron
      transport or it is lost in the form of fluorescence and thermal emission. While
      fluorescence can be readily measured, the detection of thermal deactivation
      processes can be achieved by the photoacoustic technique. In that case, the
      pressure wave generated by the thermal deactivations in a sample irradiated with
      modulated light is detected by a sensitive microphone. The relationships between
      the yield of fluorescence and thermal emissions measured simultaneously were
      analyzed by using a spinach photosystem II (PSII)-enriched preparation. It is
      shown that the quenching of fluorescence due to the photochemical activity of the
      preparations (photochemical quenching) increases in proportion to the fraction of
      thermal deactivations that is not immediately released as heat but is stored in
      photochemical intermediates (energy-storage yield) as the intensity of the
      photoacoustic modulated measuring beam (35 Hz) is decreased. Maximal levels of
      fluorescence and thermal emissions were both decreased in similar proportions
      upon photoreduction of pheophytin (Pheo), the primary acceptor of PSII. The
      variable components of fluorescence and thermal emissions were strongly decreased
      upon depletion of Mn from the Mn complex that catalyzes water oxidation and were
      recovered proportionally during reconstitution with Mn2+ at various Mn2+/reaction
      center ratios. Finally, depletion of Mn from the Mn complex together with the Fe
      of the QA-Fe-QB complex that is composed of the secondary quinone acceptors of
      PSII resulted in an increased initial level of fluorescence Fo and in the loss of
      the variable components of fluorescence and thermal emissions. The initial Fo and
      the variable components could be partially recovered by reconstitution of both
      donor and acceptor sides with Mn2+, Co2+, HCO3- and plastoquinone. It is
      concluded that the photochemical fluorescence quenching is correlated with a
      simultaneous "quenching" of a variable component of thermal emission. It is
      proposed that the measured component of variable thermal emission is related to
      the decay of the pair [P680+ Pheo-]. The suggestion is also made that a
      bicarbonate-induced protonation of reduced QA or QB or conformational change in
      the PSII complex, or both, adds an additional entropic factor to the variable
      thermal emission component.

PMID- 8278381
TI  - Delineation of the subunit composition of human proteasomes using antisera
      against the major histocompatibility complex-encoded LMP2 and LMP7 subunits.
AB  - The products of the Lmp2 and Lmp7 genes located in the major histocompatibility
      complex (MHC) class II region are postulated to form part of the proteasome
      complex. This large, multisubunit complex forms the major, nonlysosomal
      proteolytic machinery for the degradation of endogenous proteins and has been
      suggested to play a role in the processing of antigens presented by MHC class I
      molecules. The role of the MHC-encoded subunits within the proteasome has however
      remained enigmatic. To study this role, we have raised antibodies to recombinant
      LMP2 and LMP7 proteins. Under denaturing conditions, the anti-LMP7 serum
      recognizes one subunit of proteasome, whereas the anti-LMP2 serum recognizes two
      subunits, which may represent different forms of LMP2. The specificity of these
      sera has been ascertained by a lack of reactivity in T2 cells, which lack both
      genes. Furthermore under native conditions the anti-LMP2 serum immunoprecipitates
      a complex that is similar to proteasome but lacks several subunits, including
      LMP7. Preclearing experiments using this serum and a monoclonal antibody (2-17)
      specific for the non-MHC-encoded C2 proteasome subunit demonstrate that the
      complexes recognized by these two sera are distinct and that four subunits are
      unique to the complex precipitated by the anti-LMP2 serum. Interestingly, the
      different forms of LMP2 are segregated between these complexes. The relationship
      of the two complexes is discussed.

PMID- 8278382
TI  - A granulocyte inhibitory protein overexpressed in chronic renal disease regulates
      expression of interleukin 6 and interleukin 8.
AB  - Growing evidence suggests that cytokine expression is influenced by locally
      produced mediators, thus modifying the pluripotential effects of cytokines toward
      a tissue-specific inflammatory reaction. The granulocyte inhibitory protein
      (GIP), a 23-kDa protein found to be significantly overexpressed in patients with
      chronic renal failure, increases autocrine transcription and expression of
      interleukin (IL) 6 and IL-8 in human mesangial cells. Moreover, GIP alone induced
      the transcription of c-jun mRNA; however, in combination with IL-6, it stimulated
      de novo synthesis of DNA and the transcription of both c-jun and c-fos genes. The
      data suggest that the overall effect of GIP results in the modulation of the
      glomerular response to injury and contributes to the progression of
      glomerulosclerosis.

PMID- 8278383
TI  - Osmoprotective compounds in the Plumbaginaceae: a natural experiment in metabolic
      engineering of stress tolerance.
AB  - In common with other zwitterionic quarternary ammonium compounds (QACs), glycine
      betaine acts as an osmoprotectant in plants, bacteria, and animals, with its
      accumulation in the cytoplasm reducing adverse effects of salinity and drought.
      For this reason, the glycine betaine biosynthesis pathway has become a target for
      genetic engineering of stress tolerance in crop plants. Besides glycine betaine,
      several other QAC osmoprotectants have been reported to accumulate among
      flowering plants, although little is known about their distribution, evolution,
      or adaptive value. We show here that various taxa of the highly stress-tolerant
      family Plumbaginaceae have evolved four QACs, which supplement or replace glycine
      betaine-namely, choline O-sulfate and the betaines of beta-alanine, proline, and
      hydroxyproline. Evidence from bacterial bioassays demonstrates that these QACs
      function no better than glycine betaine as osmoprotectants. However, the
      distribution of QACs among diverse members of the Plumbaginaceae adapted to
      different types of habitat indicates that different QACs could have selective
      advantages in particular stress environments. Specifically, choline O-sulfate can
      function in sulfate detoxification as well as in osmoprotection, beta-alanine
      betaine may be superior to glycine betaine in hypoxic saline conditions, and
      proline-derived betaines may be beneficial in chronically dry environments. We
      conclude that the evolution of osmoprotectant diversity within the Plumbaginaceae
      suggests additional possibilities to explore in the metabolic engineering of
      stress tolerance in crops.

PMID- 8278384
TI  - Direct observation of better hydration at the N terminus of an alpha-helix with
      glycine rather than alanine as the N-cap residue.
AB  - The structural basis for the stability of N termini of helices has been analyzed
      by thermodynamic and crystallographic studies of three suitably engineered
      mutants of the barley chymotrypsin inhibitor 2 with Ser, Gly, or Ala at the N-cap
      position (residue 31). Each mutant has a well-organized shell of hydration of the
      terminal NH groups of the helix. The three structures are virtually
      superimposable (rms separations for all atoms, including the common water
      molecules, are 0.15-0.17 A) and show neither changes in conformation at the site
      of substitution nor changes in the crystal packing. The only changes on going
      from Ser-31 to Ala-31 to Gly-31 are in the position of a water molecule (Wat
      116). This is bound to the Ser-O gamma atom in the Ser-31 structure but is in a
      weak hydrogen bonding position with the NH of residue 34 (O ... N = 3.28 A) in
      the Ala-31 mutant, partly replacing the strong Ser-31-O gamma ... N34 hydrogen
      bond (O ... N = 2.65 A). The corresponding water molecule completely replaces the
      Ser hydroxyl hydrogen bond to N34 on mutation to Gly (2.74 A). The only other
      change between the three structures is an additional water molecule in the Ala-31
      structure (Wat-150) that partly compensates for the weak Wat-116 ... N34 hydrogen
      bond. Perturbation of solvation by the side chain of Ala is consistent with
      earlier hypotheses on the importance of exposure of the termini of helices to the
      aqueous solvent.

PMID- 8278385
TI  - Ala-->Gly mutation in the putative catalytic loop confers temperature sensitivity
      on Ros, insulin receptor, and insulin-like growth factor I receptor protein
      tyrosine kinases.
AB  - Temperature-sensitive mutations in the avian sarcoma virus UR2 oncogene ros,
      encoding a receptor protein-tyrosine kinase (PTK), were identified. The Ala385-
      >Gly change mapping within the highly conserved RDLAARN motif in the Ros kinase
      domain was responsible for the temperature-sensitive phenotype. Based on the
      sequence homology of all known protein kinases and the crystalline structure of
      the cAMP-dependent protein kinase, this conserved region probably represents the
      PTK catalytic loop. The same mutation when introduced into the human insulin and
      insulin-like growth factor I receptors made these PTKs temperature sensitive in
      both biological function and kinase activity. Our results support the presumed
      catalytic role of this highly conserved sequence in PTKs. Due to its highly
      conserved nature, we predict that the same mutation would probably confer
      temperature sensitivity on other PTKs.

PMID- 8278386
TI  - Early auxin-induced genes encode short-lived nuclear proteins.
AB  - The plant growth hormone indoleacetic acid (IAA) transcriptionally activates gene
      expression in plants. Some of the genes whose expression is induced by IAA encode
      a family of proteins in pea (PS-IAA4 and PS-IAA6) and Arabidopsis (IAA1 and IAA2)
      that contain putative nuclear localization signals that direct a beta
      glucuronidase reporter protein into the nucleus. Pulse-chase and
      immunoprecipitation experiments have defined the t1/2 of the PS-IAA4 and PS-IAA6
      proteins to be 8 and 6 min, respectively. Their most prominent feature is the
      presence of a beta alpha alpha motif similar to the beta-sheet DNA-binding domain
      found in prokaryotic repressors of the Arc family. Based on these data, we
      suggest that plant tissues express short-lived nuclear proteins as a primary
      response to IAA. We propose that these proteins act as activators or repressors
      of genes responsible for mediating the various auxin responses.

PMID- 8278387
TI  - Quantitative magnetic resonance imaging of human brain perfusion at 1.5 T using
      steady-state inversion of arterial water.
AB  - We report our experience using a noninvasive magnetic resonance technique for
      quantitative imaging of human brain perfusion at 1.5 T. This technique uses
      magnetically inverted arterial water as a freely diffusible blood flow tracer. A
      perfusion image is calculated from magnetic resonance images acquired with and
      without arterial blood inversion and from an image of the apparent spin-lattice
      relaxation time. Single-slice perfusion maps were obtained from nine volunteers
      with approximately 1 x 2 x 5-mm resolution in an acquisition time of 15 min.
      Analysis yielded average perfusion rates of 93 +/- 16 ml.100 g-1.min-1 for gray
      matter, 38 +/- 10 ml.100 g-1.min-1 for white matter, and 52 +/- 8 ml.100 g-1.min
      1 for whole brain. Significant changes in perfusion were observed during
      hyperventilation and breath holding. This technique may be used for quantitative
      measurement of perfusion in human brain without the risks and expense of methods
      which use exogenous tracers.

PMID- 8278388
TI  - Physical association between nonhomologous chromosomes precedes distributive
      disjunction in yeast.
AB  - During meiosis homologous chromosomes normally pair, undergo reciprocal
      recombination, and then segregate from each other. Distributive disjunction is
      the meiotic segregation that is observed in the absence of homologous
      recombination and can occur for both nonrecombinant homologous chromosomes and
      completely nonhomologous chromosomes. While the mechanism of distributive
      disjunction is not known, several models have been presented that either involve
      or are completely independent of interactions between the segregating
      chromosomes. In this report, we demonstrate that distributive disjunction in
      Saccharomyces cerevisiae is preceded by an interaction between nonhomologous
      chromosomes.

PMID- 8278389
TI  - The mitogen-regulated protein/proliferin transcript is degraded in primary mouse
      embryo fibroblast but not 3T3 nuclei: altered RNA processing correlates with
      immortalization.
AB  - An understanding of what changes occur in the control of gene expression when
      mammalian cells "spontaneously" immortalize is important to our knowledge of how
      cancer develops. We describe here an alteration in regulation that occurs when
      primary mouse embryo fibroblasts (MEFs) are immortalized according to a 3T3
      regimen. Mitogen-regulated protein/proliferin mRNA is undetectable in northern
      blots of RNA from (mortal) MEFs, whereas it is readily detected in immortal 3T3
      cell lines derived from the MEFs. Incompletely processed nuclear transcripts of
      the mitogen-regulated protein/proliferin gene can be detected in MEF RNA
      preparations by northern blotting and reverse transcriptase polymerase chain
      reaction analyses, although at roughly half the abundance observed in 3T3 cells.
      We hypothesize that some attribute of the primary unprocessed transcript
      determines its assignment to this unique degradative pathway. These results
      reveal that during passage of MEFs according to a 3T3 regimen the ability of the
      primary cells to suppress the expression of certain genes by degrading the
      nuclear transcript is lost concomitantly with immortalization.

PMID- 8278390
TI  - In vivo functional protein-protein interaction: nuclear targeted hsp90 shifts
      cytoplasmic steroid receptor mutants into the nucleus.
AB  - In target tissue extracts, heat shock protein hsp90 has been found associated to
      all unliganded steroid receptors. Modulation of important functions of these
      receptors, including prevention of DNA binding and optimization of
      transcriptional activity, has been attributed to hsp90. However no unequivocal in
      vivo demonstration of interaction between receptors and hsp90 has been presented.
      We targeted chicken hsp90, a mainly cytoplasmic protein, with the nucleoplasmin
      nuclear localization signal (90NLS). After transfection into COS-7 cells, 90NLS
      was found in the nucleus with specific immunofluorescence and confocal microscopy
      techniques. A human glucocorticosteroid receptor mutant devoid of NLS sequence
      was also expressed in COS-7 cells and found exclusively cytoplasmic. Coexpression
      of 90NLS and of the cytoplasmic human glucocorticosteroid receptor mutant led to
      complete nuclear localization of the receptor, indicating its piggyback transport
      by 90NLS and thus physical and functional interaction between the two proteins in
      the absence of hormone. The same nuclear localization was obtained after
      cotransfection of 90NLS and a cytoplasmic rabbit progesterone receptor mutant.
      Finally, coexpression of wild-type rabbit progesterone receptor (nuclear) and
      wildtype hsp90 (cytoplasmic) into COS-7 cells provoked partial relocalization of
      hsp90 into the nucleus. These experiments lay the groundwork on which to study
      hsp90 as a chaperone, regulating activities of steroid receptors and possibly
      participating in their nuclear-cytoplasmic shuttling.

PMID- 8278391
TI  - Gamma delta T cells contribute to immunity against the liver stages of malaria in
      alpha beta T-cell-deficient mice.
AB  - The functional role of gamma delta T cells (expressing the gamma delta
      heterodimeric T-cell receptor for antigen) in infectious diseases remains largely
      unknown. We have therefore attempted to define the possible role of these T cells
      in the immune response against the various developmental stages of malaria
      parasites. For this purpose, we monitored the immune response and the development
      of liver and blood stages of Plasmodium yoelii, a rodent malaria parasite, in
      immunized and nonimmunized alpha beta T-cell-deficient and gamma delta T-cell
      deficient mice. Immunization of alpha beta T-cell-deficient mice with irradiated
      sporozoites induced an immune response that significantly inhibited the
      development of the parasite's liver stages. This inhibitory immune response was
      abolished by an antibody-mediated transient in vivo depletion of gamma delta T
      cells. Two gamma delta T-cell clones were derived from malaria-immunized alpha
      beta T-cell-deficient mice. The adoptive transfer of one of these gamma delta T
      cell clones to normal mice inhibited the development of liver stages, following
      sporozoite inoculation. These results provide evidence for gamma delta T-cell
      mediated protective immunity against parasites, in the absence of alpha beta T
      cells. As for the blood phase of the infection, both normal mice and gamma delta
      T-cell-deficient mice cleared the blood stages of the nonlethal strain of P.
      yoelii, while alpha beta T-cell-deficient mice failed to control the parasitemia.

PMID- 8278392
TI  - Gene transfer into hematopoietic stem cells: long-term maintenance of in vitro
      activated progenitors without marrow ablation.
AB  - Adoptive transfer of genetically modified somatic cells will play an increasingly
      important role in the management of a wide spectrum of human diseases. Among the
      most appealing somatic cells as potential gene transfer vehicles are
      hematopoietic cells, because of their wide distribution and their well
      characterized capacities for proliferation, differentiation, and self-renewal.
      Genes can be readily transferred into short-lived and lineage-restricted
      hematopoietic cells, but there remains a need to develop reliable methods for
      gene transfer into hematopoietic stem cells in large animals. In this work, we
      used a gene transfer approach in which hematopoietic cells in long-term marrow
      cultures were exposed to the replication-defective retrovirus N2, bearing the
      reporter gene neo, on multiple occasions during 21 days of culture. Genetically
      marked cultured autologous cells were infused into 18 canine recipients in the
      absence of marrow-ablative conditioning. neo was detected by Southern blotting
      and/or the polymerase chain reaction in the marrow, blood, marrow-derived
      granulocyte/macrophage and erythroid progenitors, and cultured T cells in dogs
      after infusion. In most dogs, the proportion of long-term marrow culture cells
      contributing to hematopoiesis rose during the first 3 months after infusion and
      peaked within the first 6. The maximal levels attained were between 10% and 30%
      G418-resistant (neo-positive) granulocyte/macrophage progenitors. At 12 months,
      five dogs maintained greater than 10% G418-resistant progenitors, and for two of
      them this level exceeded 20%. Two dogs had greater than 5% G418-resistant
      hematopoietic progenitors at 24 months after infusion. Our data suggest that very
      primitive hematopoietic progenitors are maintained in long-term marrow cultures,
      where they can be triggered into entering the cell cycle. In vivo, these
      activated cells likely continue normal programs of proliferation,
      differentiation, and self-renewal. Their progeny can be maintained at clinically
      relevant levels for up to 2 years without the requirement that endogenous
      hematopoiesis be suppressed through chemo- or radiotherapy prior to adoptive
      transfer. Long-term marrow culture cells may thus be ideal targets for gene
      therapy involving adoptive transfer of transduced hematopoietic cells.

PMID- 8278394
TI  - UV and skin cancer: specific p53 gene mutation in normal skin as a biologically
      relevant exposure measurement.
AB  - Many human skin tumors contain mutated p53 genes that probably result from UV
      exposure. To investigate the link between UV exposure and p53 gene mutation, we
      developed two methods to detect presumptive UV-specific p53 gene mutations in UV
      exposed normal skin. The methods are based on mutant allele-specific PCRs and
      ligase chain reactions and designed to detect CC to TT mutations at codons 245
      and 247/248, using 10 micrograms of DNA samples. These specific mutations in the
      p53 gene have been reported in skin tumors. CC to TT mutations in the p53 gene
      were detected in cultured human skin cells only after UV irradiation, and the
      mutation frequency increased with increasing UV dose. Seventeen of 23 samples of
      normal skin from sun-exposed sites (74%) on Australian skin cancer patients
      contained CC to TT mutations in one or both of codons 245 and 247/248 of the p53
      gene, and only 1 of 20 samples from non-sun-exposed sites (5%) harbored the
      mutation. None of 15 biopsies of normal skin from non-sun-exposed or
      intermittently exposed sites on volunteers living in France carried such
      mutations. Our results suggest that specific p53 gene mutations associated with
      human skin cancer are induced in normal skin by solar UV radiation. Measurement
      of these mutations may be useful as a biologically relevant measure of UV
      exposure in humans and as a possible predictor of risk for skin cancer.

PMID- 8278393
TI  - Recombinant human Fab to glycoprotein D neutralizes infectivity and prevents cell
      to-cell transmission of herpes simplex viruses 1 and 2 in vitro.
AB  - Herpes simplex viruses 1 and 2 (HSV-1 and -2) are associated with a number of
      conditions of varying severity, which are only partially responsive to current
      therapies. Human antibodies to the viruses offer a potential alternative. We
      describe here the generation of panels of human monoclonal Fab fragments to HSV-1
      and -2 by panning a phage display combinatorial antibody library against whole
      lysates from the two viruses. Each lysate selected a largely distinct set of
      Fabs, although all of the Fabs were cross-reactive with both viruses. In a plaque
      reduction assay, one Fab neutralized HSV-1 at 0.25 microgram/ml (50% reduction)
      and HSV-2 at 0.05 microgram/ml. This Fab also inhibited plaque formation when
      applied to virus-infected monolayers, completely abolishing HSV-2 plaque
      development at 25 micrograms/ml 72 hr postinfection, indicating the ability of
      the Fab to prevent cell-to-cell spread of virus. The Fab was shown to recognize
      viral glycoprotein D and to neutralize virus primarily by a postattachment
      mechanism. Recombinant Fabs may be useful for topical administration, although
      whole antibody will probably be required for systemic use.

PMID- 8278395
TI  - Specific ablation of human immunodeficiency virus Tat-expressing cells by
      conditionally toxic retroviruses.
AB  - The identification of human immunodeficiency virus (HIV) as the etiologic agent
      of AIDS has led to the proposal of novel intervention strategies to block HIV
      infection and viral replication or eliminate HIV-infected cells. We have produced
      recombinant retroviruses for a molecular ablation system, whereby a toxin gene
      can be delivered to hematopoietic cells for the specific elimination of HIV Tat
      expressing cells. For this cell-specific ablation, we have coupled the
      conditional toxin herpes simplex virus type 1 thymidine kinase (tk) gene to the
      HIV-2 promoter and Tat responsive region (TAR) in order that transcriptional
      activity be under the absolute control of HIV and simian immunodeficiency virus
      Tat trans-activator proteins. Since the HIV-2 promoter has a considerable level
      of basal expression in the absence of Tat, we constructed a number of
      modifications in the HIV-2 promoter to minimize the risk of cytotoxicity to cells
      not containing HIV Tat. We demonstrate that certain promoter modifications reduce
      basal transcription while maintaining high trans-activated levels of expression
      when transfected or transduced by retroviral vectors into several different cell
      lines. In mouse and human cells infected with HIV-2 tk retroviruses, we show that
      Tat-induced expression from the HIV-2 promoter results in differential ablation
      and a massive reduction in Tat-positive cells after ganciclovir treatment. Thus,
      the retroviruses produced in these studies may be applicable to HIV ablative
      therapy.

PMID- 8278397
TI  - Mode of cell proliferation in the developing mouse neocortex.
AB  - There are two proliferative populations in the developing cerebral wall: the
      pseudostratified ventricular epithelium (PVE) and the secondary proliferative
      population (SPP). The present experiments provide on embryonic day 14 (E14) in
      the mouse direct measures of the values for the proportions of daughter cells
      that continue to proliferate (proliferative, P fraction, or P) and for those that
      leave the cell cycle (quiescent, Q fraction, or Q; Q = 1 - P) for both of these
      populations. The range of values of P for the PVE, 0.62-0.66, would provide for
      the relatively low rate of neuronal output and for an expansion of the
      proliferative population appropriate for E14. The even higher values of P for the
      SPP, 0.73-1.0, would expand this population rapidly in preparation for the high
      glial cell output to occur later in cerebral histogenesis.

PMID- 8278396
TI  - A conserved stem-loop structure in the 3' untranslated region of procyclin mRNAs
      regulates expression in Trypanosoma brucei.
AB  - African trypanosomes that cycle between mammalian hosts and the tsetse fly vector
      must be poised to survive in different environments. The control of stage
      specific gene expression is undoubtedly one of the keys to successful adaptation,
      but no regulatory elements have been defined to date. Procyclins (also known as
      procyclic acidic repetitive proteins) are specifically expressed on the surface
      of procyclic and epimastigote forms in the fly. Procyclin genes are already
      transcribed in bloodstream forms, but stable mRNA, and later the protein, are
      first detected when the parasites begin to differentiate into procyclic forms. We
      have now identified a region of 16 bases that forms part of a predicted stem-loop
      structure in the 3' untranslated regions of different procyclin mRNAs; both the
      sequence and the secondary structure of this 16-mer appear to be required for
      efficient translation of a reporter gene in procyclic forms. The level of steady
      state mRNA, its polyadenylylation, and its distribution in the cell are all
      unaffected by the presence or absence of this element. Deletion of the 16-mer
      alone reduces expression more than removal or reversal of the entire 3'
      untranslated region and flanking region, suggesting that there are additional
      negative regulatory elements in the same 3' untranslated region.

PMID- 8278398
TI  - Topography of a binding site for small amnestic peptides deduced from structure
      activity studies: relation to amnestic effect of amyloid beta protein.
AB  - Four peptides homologous to amyloid beta protein containing the Val-Phe-Phe (VFF)
      sequence administered intracerebroventricularly after training caused amnesia for
      footshock active avoidance training in mice. Results with VFF and other peptides
      containing VFF or portions thereof were used to generate a topographic map for a
      hypothetical binding surface for amnestic peptides, termed Z. Effects on
      retention of footshock active avoidance training were rationalized in terms of
      fit to Z, making possible design of potential memory-modulating peptidic and
      nonpeptidic substances. Three peptides that neither improved nor impaired
      retention blocked the amnestic effects of beta-(12-28), a peptide homologous to
      amyloid beta protein, opening the way to development of substances that can
      antagonize the neurotoxic effects of amyloid beta protein on neural structures
      and thus attenuate symptoms and progression of Alzheimer disease.

PMID- 8278399
TI  - Kappa B enhancer-binding complexes that do not contain NF-kappa B are
      developmentally regulated in mammalian brain.
AB  - DNA-binding complexes which are temporally regulated in developing rat brain have
      been identified by their ability to interact with the kappa B enhancer sequence
      in electrophoretic mobility-shift assays. These complexes, referred to as
      developing-brain factors (DBFs) 1 and 2, are abundant in nuclear extracts from
      developing rat brain through postnatal day 2 and decline to nearly undetectable
      levels by postnatal day 7. DBFs were not detected in extracts from cultured cell
      lines or in tissues other than the developing brain. The highest level of DBF DNA
      binding activity was observed in developing cortex, and the lowest in cerebellum.
      In UV crosslinking experiments, a labeled kappa B oligonucleotide probe
      crosslinked 110- and 115-kDa proteins from DBF complexes. DBFs are likely to be
      involved in the regulation of transcriptional events which take place during
      brain development.

PMID- 8278400
TI  - gamma-Aminobutyric acid is an inhibitory neurotransmitter restricting the release
      of luteinizing hormone-releasing hormone before the onset of puberty.
AB  - To test the hypothesis that the pubertal increase in luteinizing hormone
      releasing hormone (LHRH) release is withheld by a dominant inhibitory neuronal
      system, the role of gamma-aminobutyric acid (GABA), a known inhibitory
      neurotransmitter, in the control of LHRH release was examined in conscious female
      monkeys at the prepubertal and pubertal stages using a push-pull perfusion
      method. GABA, bicuculline (a GABAA receptor blocker), and 2-hydroxysaclofen (a
      GABAB receptor blocker) were directly infused into the stalk-median eminence
      while perfusates were collected for LHRH determination. Bicuculline, but not
      saclofen, induced a large and prompt increase in LHRH release in prepubertal
      monkeys, whereas it stimulated LHRH release slightly in pubertal monkeys. In
      contrast, GABA suppressed LHRH release in pubertal, but not prepubertal, monkeys.
      These differential effects of GABA and the GABA antagonist on LHRH release in the
      two developmental stages were due to an age factor rather than to the steroid
      hormonal background. Moreover, GABA release in the stalk-median eminence of
      prepubertal monkeys was much higher than that in pubertal monkeys. Thus, the
      results suggest that in the prepubertal period there is a powerful GABA
      inhibition of the LHRH neurosecretory system: infusions of GABAA, but not GABAB,
      antagonists stimulate LHRH release by removal of the endogenous GABA inhibition,
      whereas exogenous GABA is ineffective because of high endogenous GABA levels. The
      decrease of this tonic inhibition may be a key factor for the onset of puberty in
      non-human primates.

PMID- 8278401
TI  - Role of septal vasopressin innervation in paternal behavior in prairie voles
      (Microtus ochrogaster).
AB  - After being paired with females, male prairie voles show major changes in their
      social behaviors among which is an increase in paternal responsiveness. These
      changes are accompanied by fluctuations in the density of the [Arg8]vasopressin
      immunoreactive (AVP-ir) fibers in the lateral septum, suggesting that septal AVP
      might be involved in these changes. To explore a possible involvement of septal
      AVP in paternal responsiveness, we tested whether injections of saline, AVP, or
      the V1a receptor antagonist [1-(beta-mercapto-beta, beta
      cyclopentamethylenepropionic acid),2-(O-methyltyrosine]AVP [d(CH2)5Tyr(Me)AVP]
      into the lateral septum influenced the four most prominent paternal activities
      displayed by male prairie voles; grooming, crouching over, contacting, and
      retrieving pups. In a first experiment, sexually inexperienced males received a
      single injection of AVP, saline, or d(CH2)5Tyr(Me)AVP in the lateral septum,
      after which their paternal responsiveness was recorded during a 10-min period.
      AVP-injected animals spent more time contacting and crouching over pups, while
      d(CH2)5Tyr(Me)AVP-injected animals spent less time grooming pups than saline
      injected animals. In a follow-up study, one group of animals received an
      injection of AVP preceded by an injection of saline or d(CH2)5Tyr(Me)-AVP into
      the lateral septum. A second group of animals received an injection of saline
      preceded by an injection of saline or d(CH2)5Tyr(Me)AVP into the lateral septum.
      In both groups, animals spent less time grooming, crouching over, and contacting
      pups if they had first been injected with d(CH2)5Tyr(Me)AVP. Control experiments
      suggested that the effects of AVP on paternal responsiveness were dose- and site
      specific. These data suggest that septal AVP enhances paternal responsiveness by
      a V1a receptor-mediated mechanism.

PMID- 8278402
TI  - p53 binds single-stranded DNA ends and catalyzes DNA renaturation and strand
      transfer.
AB  - The p53 tumor-suppressor protein has previously been shown to bind double
      stranded and single-stranded DNA. We report that the p53 protein can bind single
      stranded DNA ends and catalyze DNA renaturation and DNA strand transfer. Both a
      bacterially expressed wild-type p53 protein and a glutathione S-transferase-wild
      type p53 fusion protein catalyzed renaturation of different short (25- to 76-nt)
      complementary single-stranded DNA fragments and promoted strand transfer between
      short (36-bp) duplex DNA and complementary single-stranded DNA. Mutant p53 fusion
      proteins carrying amino acid substitutions Glu-213, Ile-237, or Tyr-238, derived
      from mutant p53 genes of Burkitt lymphomas, failed to catalyze these reactions.
      Wild-type p53 had significantly higher binding affinity for short (36- to 76-nt)
      than for longer (> or = 462-nt) single-stranded DNA fragments in an
      electrophoretic mobility-shift assay. Moreover, electron microscopy showed that
      p53 preferentially binds single-stranded DNA ends. Binding of DNA ends to p53
      oligomers may allow alignment of complementary strands. These findings suggest
      that p53 may play a direct role in the repair of DNA breaks, including the
      joining of complementary single-stranded DNA ends.

PMID- 8278403
TI  - The retinoblastoma gene product is a cell cycle-dependent, nuclear matrix
      associated protein.
AB  - The retinoblastoma gene product (Rb) has been established as a tumor suppressor
      and cell cycle regulator, although its mechanism of action remains obscure. The
      observations that several Rb-binding viral oncoproteins all associate with the
      nuclear matrix suggest that these interactions may occur on this structure. To
      determine whether Rb itself is a component of the matrix, we extracted
      synchronized cultured cells to isolate matrix proteins while preserving nuclear
      architecture. Immunoblot and immunolabeling data show that a significant portion
      of hypophosphorylated Rb associates with the matrix only during early G1. Mutant
      Rb in tumor cells did not associate with the matrix, whereas Rb-reconstituted
      cells contained abundant matrix-bound Rb. Rb is distributed widely throughout the
      matrix, particularly concentrated at the nuclear periphery and in nucleolar
      remnants. Core filaments of the matrix contained no detectable Rb. Our screening
      of expression libraries for potential Rb-associated proteins has identified
      several that are part of the matrix. Specifically, the peripheral matrix proteins
      lamin A and C bound Rb in vitro. We therefore suggest that Rb interactions with
      the nuclear matrix may be important for its ability to regulate cell cycle
      progression.

PMID- 8278404
TI  - The crystal structure of a mutant protein with altered but improved hydrophobic
      core packing.
AB  - The dense packing observed in protein interiors appears to be crucial for
      stabilizing the native structure--even subtle internal substitutions are usually
      destabilizing. Thus, steric complementarity of core residues is thought to be an
      important criterion for "inverse folding" predictive methods, which judge whether
      a newly determined sequence is consistent with any known folds. A major problem
      in the development of useful core packing evaluation algorithms, however, is that
      there are occasional mutations that are predicted to disrupt native packing but
      that yield an equally or more stable protein. We have solved the crystal
      structure of such a variant of lambda repressor, which, despite having three
      larger core substitutions, is more stable than the wild type. The structure
      reveals that the protein accommodates the potentially disruptive residues with
      shifts in its alpha-helical arrangement. The variant is apparently more stable
      because its packing is improved--the core has a higher packing density and little
      geometric strain. These rearrangements, however, cause repositioning of
      functional residues, which result in reduced DNA binding activity. By comparing
      these results with the predictions of two core packing algorithms, it is clear
      that the protein possesses a relatively high degree of main-chain flexibility
      that must be accounted for in order to predict the full spectrum of compatible
      core sequences. This study also shows how, in protein evolution, a particular set
      of core residue identities might be selected not because they provide optimal
      stability but because they provide sufficient stability in addition to the
      precise structure required for optimal activity.

PMID- 8278405
TI  - Extension of Autographa californica nuclear polyhedrosis virus host range by
      interspecific replacement of a short DNA sequence in the p143 helicase gene.
AB  - Recombinant baculoviruses obtained by coinfection of insect cells with Autographa
      californica and Bombyx mori nuclear polyhedrosis viruses (AcNPV and BmNPV,
      respectively) possess a wider in vitro host range than either parent virus. To
      localize the DNA sequences responsible for this species specificity, we used a
      two-step method of production and selection of recombinant viruses with altered
      specificity. Sf9 cells, which are permissive for AcNPV, were first cotransfected
      with genomic AcNPV DNA and a complete or incomplete set of BmNPV restriction
      fragments. AcNPV-BmNPV recombinants from the Sf9 supernatant were then selected
      on the basis of ability to replicate in B. mori Bm5 cells, which are not
      permissive for AcNPV. Cotransfection of AcNPV DNA with the 7.6-kbp BmNPV Sma I-C
      fragment was sufficient to produce recombinants able to infect both Sf9 and Bm5
      cells. A series of cotransfections with subclones of this fragment defined a 79
      nt sequence within the p143 helicase gene capable of extending AcNPV host range
      in vitro. In this 79-nt region, BmNPV and AcNPV differ at six positions,
      corresponding to four amino acid substitutions. The involvement of the 79-nt
      region in species specificity control was confirmed by cotransfecting AcNPV DNA
      and gel-purified polymerase chain reaction products derived from the BmNPV p143
      gene. Replacement in the AcNPV genome of three AcNPV-specific amino acids by the
      three corresponding BmNPV-specific amino acids at positions 556, 564, and 577 of
      the p143 protein extends AcNPV host range to B. mori larvae.

PMID- 8278406
TI  - Transplantation of glial cells enhances action potential conduction of
      amyelinated spinal cord axons in the myelin-deficient rat.
AB  - A central issue in transplantation research is to determine how and when
      transplantation of neural tissue can influence the development and function of
      the mammalian central nervous system. Of particular interest is whether
      electrophysiological function in the traumatized or diseased mammalian central
      nervous system can be improved by the replacement of cellular elements that are
      missing or damaged. Although it is known that transplantation of neural tissue
      can lead to functional improvement in models of neurological disease
      characterized by neuronal loss, less is known about results of transplantation in
      disorders of myelin. We report here that transplantation of glial cells into the
      dorsal columns of neonatal myelin-deficient rat spinal cords leads to myelination
      and a 3-fold increase in conduction velocity. We also show that impulses can
      propagate into and out of the transplant region and that axons myelinated by
      transplanted cells do not have impaired frequency-response properties. These
      results demonstrate that myelination following central nervous system glial cell
      transplantation enhances action potential conduction in myelin-deficient axons,
      with conduction velocity approaching normal values.

PMID- 8278407
TI  - Calcium oscillations in pituitary gonadotrophs: comparison of experiment and
      theory.
AB  - We have developed a mathematical model that describes several aspects of agonist
      induced Ca2+ signaling in single pituitary gonadotrophs. Our model is based on
      fast activation of the inositol 1,4,5-trisphosphate (InsP3) receptor Ca2+
      channels at low free cytosolic Ca2+ concentration ([Ca2+]i) and slow inactivation
      at high [Ca2+]i. Previous work has shown that these gating properties, when
      combined with a Ca(2+)-ATPase, are sufficient to generate simulated Ca2+
      oscillations. The Hodgkin-Huxley-like description we formulate here incorporates
      these different gating properties explicitly and renders their effects
      transparent and easy to modulate. We introduce regulatory mechanisms of channel
      opening which enable the model, both in the absence and in the presence of Ca2+
      entry, to give responses to a wide range of agonist doses that are in good
      agreement with experimental findings, including subthreshold responses,
      superthreshold oscillations with frequency determined by [InsP3], and
      nonoscillatory "biphasic" responses followed occasionally by small-amplitude
      oscillations. A particular added feature of our model, enhanced channel opening
      by reduced concentration of Ca2+ in the lumen of the endoplasmic reticulum,
      allows oscillations to continue during pool depletion. The model predicts that
      ionomycin and thapsigargin can induce oscillations with basal [InsP3] and zero
      Ca2+ entry, while Ca2+ injection cannot. Responses to specific pairings of sub-
      or superthreshold stimuli of agonist, ionomycin, and thapsigargin are also
      correctly predicted. Since this model encompasses a wide range of observed
      dynamic behaviors within a single framework, based on well-established
      mechanisms, its relevance should not be restricted to gonadotrophs.

PMID- 8278408
TI  - Pattern recognition, chaos, and multiplicity in neural networks of excitable
      systems.
AB  - We study a neural network composed of excitable FitzHugh neurons that interact by
      diffusive type connections. Patterns of neural activity may be stored by a
      Hebbian rule. The stored patterns are recalled and given by the transient
      activity of the neurons after the network has been perturbed by related patterns
      and relaxes back to its steady state. Periodic perturbations of the network are
      repeated requests for computations and result in simple periodic, complex
      periodic, and chaotic responses and corresponding computational performances.

PMID- 8278409
TI  - A method to determine the ability of drugs to diffuse through the blood-brain
      barrier.
AB  - A method has been devised for predicting the ability of drugs to cross the blood
      brain barrier. The criteria depend on the amphiphilic properties of a drug as
      reflected in its surface activity. The assessment was made with various drugs
      that either penetrate or do not penetrate the blood-brain barrier. The surface
      activity of these drugs was quantified by their Gibbs adsorption isotherms in
      terms of three parameters: (i) the onset of surface activity, (ii) the critical
      micelle concentration, and (iii) the surface area requirement of the drug at the
      air/water interface. A calibration diagram is proposed in which the critical
      micelle concentration is plotted against the concentration required for the onset
      of surface activity. Three different regions are easily distinguished in this
      diagram: a region of very hydrophobic drugs which fail to enter the central
      nervous system because they remain adsorbed to the membrane, a central area of
      less hydrophobic drugs which can cross the blood-brain barrier, and a region of
      relatively hydrophilic drugs which do not cross the blood-brain barrier unless
      applied at high concentrations. This diagram can be used to predict reliably the
      central nervous system permeability of an unknown compound from a simple
      measurement of its Gibbs adsorption isotherm.

PMID- 8278410
TI  - Induction of apoptotic DNA damage and cell death by activation of the
      sphingomyelin pathway.
AB  - The potential involvement of ceramide-related signaling processes in the
      induction of apoptosis by tumor necrosis factor alpha was assessed by multiple
      biochemical strategies in the human leukemic cell lines HL-60 and U937 and the
      murine fibrosarcoma cell lines L929/LM and WEHI 164/13. Exposure of these cells
      to tumor necrosis factor alpha resulted in internucleosomal cleavage of genomic
      DNA, yielding laddered patterns of oligonucleosomal fragments characteristic of
      apoptosis when resolved by agarose gel electrophoresis; similar responses were
      observed after exposure to exogenous sphingomyelinase or synthetic ceramides.
      Quantitative spectrofluorophotometry demonstrated that these treatments promoted
      time- and concentration-dependent degradation of DNA, resulting in the formation
      of and eventual release of small DNA fragments (< or = 3.0 kb). Corresponding
      damage to bulk DNA was demonstrated by enhanced-fluorescence alkaline unwinding
      analysis. DNA fragmentation was not induced by phospholipase C or synthetic
      diglyceride; in fact, the effects of sphingomyelinase and ceramide were
      substantially reduced by coexposure to these agents, suggesting opposing roles
      for diglyceride- and ceramide-mediated signals in the regulation of apoptosis.
      Phospholipase A2 and arachidonic acid failed to promote DNA fragmentation, as did
      phospholipase D. Characterization of DNA strand breaks by alkaline and neutral
      elution analyses confirmed that ceramide action was restricted to breakage of
      mature, double-stranded DNA but not of nascent DNA. The induction of DNA damage
      was associated with appearance of apoptotic morphology and decreased
      clonogenicity. These results demonstrate that the ceramide-dependent signaling
      system selectively induces apoptosis and raise the possibility that ceramide
      activated enzymes represent important components in a signaling cascade involved
      in the regulation of programmed cell death.

PMID- 8278411
TI  - Cloning of the cellular receptor for amphotropic murine retroviruses reveals
      homology to that for gibbon ape leukemia virus.
AB  - The host and tissue specificity of retrovirus infection is largely determined by
      specific cellular receptors that mediate virus entry. Genes encoding these
      receptors are widely distributed in the genome, and the receptors identified to
      date show no sequence similarity. We have identified the cellular receptor for
      amphotropic murine retroviruses, Ram-1, by screening a rat cDNA expression
      library introduced into amphotropic virus-resistant hamster cells. The 656-amino
      acid receptor is homologous to the gibbon ape leukemia virus receptor at both
      hydrophobic termini but is highly divergent in the central hydrophilic region.
      Both receptors appear to be integral membrane proteins having multiple membrane
      spanning regions. Identification of this family of receptors will help define the
      evolutionary relationship between retroviruses and their cellular receptors.

PMID- 8278412
TI  - Construction of libraries enriched for sequence repeats and jumping clones, and
      hybridization selection for region-specific markers.
AB  - We describe a simple and rapid method for constructing small-insert genomic
      libraries highly enriched for dimeric, trimeric, and tetrameric nucleotide repeat
      motifs. The approach involves use of DNA inserts recovered by PCR amplification
      of a small-insert sonicated genomic phage library or by a single-primer PCR
      amplification of Mbo I-digested and adaptor-ligated genomic DNA. The genomic DNA
      inserts are heat denatured and hybridized to a biotinylated oligonucleotide. The
      biotinylated hybrids are retained on a Vectrex-avidin matrix and eluted
      specifically. The eluate is PCR amplified and cloned. More than 90% of the clones
      in a library enriched for (CA)n microsatellites with this approach contained
      clones with inserts containing CA repeats. We have also used this protocol for
      enrichment of (CAG)n and (AGAT)n sequence repeats and for Not I jumping clones.
      We have used the enriched libraries with an adaptation of the cDNA selection
      method to enrich for repeat motifs encoded in yeast artificial chromosomes.

PMID- 8278413
TI  - Techniques for measuring sulcal/gyral patterns in the brain as visualized through
      magnetic resonance scanning: BRAINPLOT and BRAINMAP.
AB  - A method for measuring sulcal and gyral patterns, using data derived from
      magnetic resonance (MR) scanning, is described. This method can be applied
      through two newly developed computer programs, BRAINPLOT and BRAINMAP. These
      programs provide quantitative measures of brain surface pattern. The method has
      been validated with postmortem brains, phantoms, and human MR data. The method is
      robust to detecting differences in brain surface anatomy between atrophic and
      nonatrophic brains. It appears to offer an efficient, fully automated, and
      accurate method for analyzing the large amounts of information generated through
      in vivo neuroimaging techniques.

PMID- 8278414
TI  - How frequent are correlated changes in families of protein sequences?
AB  - A loss-of-function point mutation in a protein is often rescued by an additional
      mutation that compensates for the original physical change. According to one
      hypothesis, such compensation would be most effective in maintaining a structural
      motif if the two mutated residues were spatial neighbors. If this hypothesis were
      correct, one would expect that many such compensatory mutations have occurred
      during evolution and that present-day protein families show some degree of
      correlation in the occurrence of amino acid residues at positions whose side
      chains are in contact. Here, a statistical theory is presented which allows
      evaluation of correlations in a family of aligned protein sequences by assigning
      a scalar metric (such as charge or side-chain volume) to each type of amino acid
      and calculating correlation coefficients of these quantities at different
      positions. For the family of myoglobins it is found that there is a high
      correlation between fluctuations in neighboring charges. The correlation is close
      to what would be expected for total conservation of local charge. For the metric
      side-chain volume, on the other hand, no correlation could be found.

PMID- 8278415
TI  - Research on the Project must be made public.

PMID- 8278416
TI  - Complex reactions requiring empathy and knowledge. Psychological aspects of acute
      pain.
AB  - 1. Pain may change the personality: some people can become irritated with the
      disruption caused to their life by pain. 2. Nurses' attitudes may affect the way
      patients express their pain. 3. It is essential to provide continuity of care and
      clear communication channels, not only between nurses and patients, but between
      all members of the healthcare team.

PMID- 8278417
TI  - Optimum use of limited resources. Structured teaching in the clinical area.
AB  - 1. Structured teaching requires written teaching plans. 2. A teaching plan should
      describe objectives, teaching methods and methods of assessment. 3. Explanation,
      demonstration and practice are key stages in teaching skills in the clinical
      area. 4. NVQs can be adapted to form practical teaching plans.

PMID- 8278418
TI  - A standard to meet high expectations. Assuring quality care for families of
      intensive care patients.
AB  - 1. To give truly holistic care, nurses need to appreciate the family stress
      response to critical care hospitalisation. 2. Standard setting is an ideal way of
      meeting relatives' self-perceived needs in intensive care. 3. All staff should be
      involved with implementation for it to be successful.

PMID- 8278419
TI  - Evaluation is the key to success. A nurse-led tuberculosis contact tracing
      service.
AB  - 1. It is important that health staff increase their knowledge of TB. 2. The
      development of nursing standards is essential to the efficient running of a
      contact tracing service. 3. Patient information is offered using the health
      belief model.

PMID- 8278420
TI  - Piercing the veil of the future. A review of the Delphi method of research.
AB  - 1. The Delphi method aims to obtain the most reliable consensus of opinion of a
      group of experts. 2. This is done by a seven-step process using the method. 3.
      There are advantages and disadvantages to using this method; they arise from the
      respondents, the researcher and the responses given. 4. The final result obtained
      becomes a kind of historical action research picture of the time it was
      undertaken.

PMID- 8278421
TI  - "Do you mean that Mummy is going to die?" Caring for bereaved children.
AB  - 1. Children need to be prepared for a terminally ill parent's death. 2. They
      should be separated from the family for as little as possible. 3. Children who
      have been through this experience valued being included in the care and given
      information in a way that could be understood. 4. Carers who can rely on support
      and know how to get in touch with health professionals feel more confident about
      handling the children's uncertainties about the situation.

PMID- 8278422
TI  - The use of insulin in diabetes mellitus.
AB  - 1. The DNA structure of human insulin is very similar to animal insulin. 2. Many
      insulin preparations are available in order to achieve the best possible control.
      3. Care needs to be taken with regard to insulin administration in order to avoid
      complications.

PMID- 8278423
TI  - A confident start to a new relationship. Biological and psychological aspects of
      breastfeeding.
AB  - 1. The biological and psychological aspects of breastfeeding (along with the
      common problems) need to be considered if success is to occur. 2. Most mothers
      can breastfeed. 3. Mothers with severe anatomical abnormalities, who are HIV
      positive, have active TB or whose children have inherited mono- or disaccharide
      intolerances should not breastfeed. 4. It is important not to induce guilt (and
      sour the mother/child relationship) if a mother does not choose to breastfeed.

PMID- 8278424
TI  - Look through the parents' eyes. Helping parents of children with a learning
      disability.
AB  - 1. The loss suffered by parents of children with learning disabilities is similar
      in some ways to a grief response, and must be clearly acknowledged. 2. While
      forming an identifiable group, parents of children with learning disabilities
      have individual abilities and needs both as people and as parents. 3. Adjusting
      to life with a child with a learning disability is often a long process marked by
      times of crisis, when extra professional intervention may be necessary. 4.
      Parents and professionals can work together, learning from each other and
      ultimately increasing the quality of life for the person with the learning
      disability.

PMID- 8278425
TI  - Towards better care for women. Understanding fungating breast lesions.
AB  - 1. Although statistically affecting a minority of women with breast cancer,
      fungating breast lesions are a significant problem to those affected. 2. Evidence
      that early detection prevents development of advanced breast cancer is currently
      contestable. 3. Community nurses can help in the education, early detection and
      support of women with breast cancer. They can also give information and support
      to those undergoing treatment for fungating wounds. 4. There are several current
      palliative surgical and medical treatments for women with fungating tumours.

PMID- 8278426
TI  - Testing: a double-edged sword.

PMID- 8278427
TI  - Escape deficits induced by uncontrollable foot-shock in recombinant inbred
      strains of mice.
AB  - Although uncontrollable stressors reliably induce numerous behavioral
      disturbances, considerable interindividual variability exists in this respect.
      Inasmuch as genetic factors may be fundamental in determining vulnerability to
      stressor effects, the present investigation assessed alterations in escape
      performance following exposure to uncontrollable foot-shock in the BALB/cByJ and
      C57BL/6ByJ mice and seven recombinant inbred strains. Exposure to uncontrollable
      foot-shock disrupted shuttle escape performance in a strain-specific manner;
      however, any differences due to gender were not particularly remarkable. The
      profile of stressor effects in the recombinant strains (i.e., performance
      deficits greater, lesser or intermediate to the progenitor strains) suggest that
      the stressor effects on escape performance may be subserved by two or more
      genetic determinants. The findings are related to central mechanisms that may
      potentially account for strain differences.

PMID- 8278428
TI  - Mu-opiate receptor binding and function in HOT and COLD selected lines of mice.
AB  - mu-Opiate receptor binding and function were examined in mice selectively bred
      for sensitivity (COLD) and resistance (HOT) to ethanol-induced hypothermia. These
      mice also have differential hypothermic sensitivity to mu-opiates. mu-Opiate
      receptor density was higher in the frontal cortex of HOT mice compared with COLD
      mice, but was the same in other brain areas. In addition, there were no line
      differences in Kd values. Basal adenylate cyclase (AC) activity was similar in
      both lines, as was the response to forskolin (FS) stimulation. Morphine was more
      effective at inhibiting FS-AC activity in the hypothalamus of HOT mice compared
      with COLD mice but was equally effective in the frontal and parietal cortex.
      There were no differences between lines in basal Ca2+, Mg2+, or Ca2+/Mg(2+)
      ATPase activity. Further, 30 min after treatment ATPase activities were not
      altered in ethanol- or levorphanol-treated mice. These results suggests that mu
      opiate biochemical pathways, but not ATPase enzyme systems, may be involved in
      mediating differential hypothermic sensitivity observed in HOT and COLD mice.

PMID- 8278429
TI  - Smoking-related subjective and physiological changes: pre- to postpuff and pre-
      to postcigarette.
AB  - Twenty-six female regular smokers participated in two sessions, smoking a
      cigarette and drinking for comparison a cup of coffee in each. Cardiovascular,
      electromyogram (EMG), motor activity, and electroencephalogram (EEG) parameters
      were assessed before and after smoking a cigarette or drinking a cup of coffee.
      The same variables were averaged for 5-s periods preceding, during, and following
      the first six puffs and sips. As the expected psychophysiological changes might
      be related to pleasure, the experimental design included both pleasant-tasting
      coffee and cigarettes and preparations manipulated to be unpleasant. Comparing
      pre/post consumption and pre/post puffing changes, heart rate increased as
      expected pre/post a cigarette but not pre/post puffing. On the other hand, there
      was no change in heart rate pre/post a cup of coffee but a transient increase
      pre/post sipping. The pre/post puffing and pre/post sipping changes in the EEG
      power distribution were similar for both drugs, occurred already in anticipation
      of puffing and sipping, and qualitatively suggested sedation as opposed to the
      pre/post cigarette arousing effects. These results might explain the observations
      of subjective tranquilizing effects during the consumption of a stimulant.
      Although the taste manipulations produced significant subjective effects, they
      did not influence the anticipatory effects.

PMID- 8278430
TI  - Effects of the combined administration of the 5-HT3 antagonist MDL 72222 and
      ethanol on conditioning in the periadolescent and adult rat.
AB  - The effects of acute ethanol and treatment with the 5-HT3 antagonist MDL 72222 on
      conditioning of a visual pattern discrimination and an olfactory context were
      examined in periadolescent (35-38-day-old) and adult (60-70-day-old) rats. In
      Experiment 1, the effects of acute ethanol exposure on conditioning of a visual
      pattern discrimination (horizontal vs. vertical black and white stripes) and an
      olfactory context were investigated. The results indicated that a moderate dose
      of ethanol, 2 g/kg, disrupted conditioning at both ages to the visual stimulus
      but not to the olfactory context in which conditioning occurred. This may reflect
      differential susceptibility of target and contextual learning to the effects of
      ethanol, or might instead confirm previous suggestions that the visual system is
      more susceptible than the olfactory system to the effects of acute ethanol
      exposure. The effects of 5.0 and 10.0 mg/kg MDL 72222 on the ethanol-induced
      impairment in pattern discrimination conditioning were examined in Experiment 2.
      Pretreatment with these doses of MDL 72222 did not reverse the cognitive
      impairments produced by acute ethanol exposure at either age. However, MDL 72222
      pretreatment attenuated the hyperlocomotion evident in ethanol-treated male and
      female periadolescents and adult females, as indexed by the number of crossovers
      during the preference test. Thus, MDL 72222 does not appear to ameliorate the
      cognitive impairment induced by acute ethanol exposure, although the antagonist
      was observed to attenuate ethanol-induced hyperlocomotion in the same test
      situation.

PMID- 8278431
TI  - Neuropeptide Y: intraaccumbens injections produce a place preference that is
      blocked by cis-flupenthixol.
AB  - Neuropeptide Y (NPY) has been localized in the nucleus accumbens (NAcc), where it
      may influence dopamine (DA) neurotransmission. Extensive data implicate NAcc DA
      in reward-related learning, raising the possibility that NPY microinjected into
      the NAcc may induce rewarding effects mediated by DA. This hypothesis was tested
      using the conditioned place preference (CPP) paradigm. Each experiment consisted
      of three distinct phase: preconditioning (three 15-min exposures to an apparatus
      with two compartments connected by a tunnel); conditioning (four 30-min pairing
      of one compartment with drug and four similar pairings of the other compartment
      with vehicle); and test (three 15-min exposures to the apparatus). A significant
      increase in the time spent in the drug-paired compartment from preconditioning to
      test was taken as evidence of a CPP. Two experiments showed that systemic (2.0
      mg/kg, IP) or intraaccumbens amphetamine (10.0 micrograms in 0.5 microliters on
      each side) produced a CPP. The third experiment showed that intraaccumbens NPY
      (0.1 micrograms in 0.5 microliter on each side) produced a CPP. This CPP was
      blocked by pretreatment with a dose of the DA receptor blocker cis-flupenthixol
      (20.0 micrograms in 0.5 microliter on each side in the NAcc) that, alone,
      produced no CPP effect. These results strongly suggest that NPY applied to the
      NAcc is rewarding. In addition, these rewarding properties of NPY may be mediated
      by DA neurotransmission.

PMID- 8278432
TI  - Environmental stimulation promotes changes in the distribution of phorbol ester
      receptors.
AB  - The translocation of protein kinase C (PKC) from the cytosol to the membrane
      might be functionally involved in learning and memory. Using [3H]-phorbol 12,13
      dibutyrate (3H-PDBu) binding three pools of binding sites could be distinguished
      in tissue preparations: Pool a comprised the soluble receptors which bound
      phorbol ester with low affinity in the absence of calcium. Pool b was composed of
      high-affinity phorbol ester binding sites identified in the soluble fraction upon
      addition of calcium. Pool c represented stably membrane-bound receptors binding
      phorbol ester independently of calcium. 3H-PDBu binding was then measured in the
      cortices and hippocampi of rats trained in an eight-arm radial maze. A
      progressive training-dependent increase of membrane-bound binding activity with a
      concomitant decrease in the soluble fraction was detected independent of learning
      the maze task. These results suggest that it is the experience of an enriched
      environment by the repeated behavioral stimulation in a maze rather than the
      acquisition of a memory task that leads to enhanced incorporation of phorbol
      ester receptors (PKC) into the cell membrane.

PMID- 8278433
TI  - Behavior-associated changes in blood pressure during heroin self-administration.
AB  - Changes in arterial blood pressure (ABP) were studied in freely moving rats
      during the development and performance of operant IV heroin self-administration
      (SA) behavior (100 micrograms/kg/injection). Heroin SA was accompanied by
      bidirectional, phasic ABP fluctuations in the absence of significant alterations
      in long-term, basal ABP levels. In trained rats, ABP gradually increased starting
      5 min before each lever-press for the drug, reached a peak at the moment of lever
      press and abruptly decreased after heroin infusion. This biphasic pattern
      corresponded to a preresponding behavioral activation followed by a postheroin
      sedation. These ABP fluctuations were absent during the initial heroin self
      injections in drug-naive rats and during the first self-injections of a session
      in trained rats. A slight hypo- and hypertension were seen in these cases,
      respectively. The postdrug ABP decrease became more pronounced after rats
      received a double dose of heroin. With training, nonreinforced lever-presses and
      sound stimulation previously associated with heroin self-injections also
      significantly decreased ABP. Thus, a gradual ABP increase appears to be an
      essential correlate of drug-seeking and -taking behavior, while a subsequent ABP
      decrease may be related to the alleviation of these behaviors by heroin and
      possibly correlate to its rewarding (euphorigenic) action.

PMID- 8278434
TI  - Development of behavioral tolerance to delta 9-THC without alteration of
      cannabinoid receptor binding or mRNA levels in whole brain.
AB  - The effect of repetitive administration of delta-9-tetrahydrocannabinol (delta 9
      THC) in mice on behavioral and biochemical tolerance was determined in this
      study. Mice were injected twice daily with 10 mg/kg delta 9-THC for 6.5 days. On
      day 8, spontaneous activity was assessed or whole-brain homogenates were prepared
      for the cannabinoid receptor binding and mRNA studies. Although a twenty
      sevenfold tolerance to delta 9-THC was observed in the behavioral assay, there
      was no significant alteration in receptor binding or mRNA levels.

PMID- 8278435
TI  - The role of nucleus accumbens dopamine in responding on a continuous
      reinforcement operant schedule: a neurochemical and behavioral study.
AB  - Two experiments were undertaken to investigate the role of nucleus accumbens
      dopamine (DA) in instrumental lever pressing on a continuous reinforcement (CRF)
      schedule. Rats trained to press a lever for food reinforcement on a CRF schedule,
      and food-deprived control rats, were implanted with dialysis probes in the
      nucleus accumbens. The day after implantation, rats were tested and dialysis
      samples were assayed for DA and the DA metabolite 3,4-dihydroxyphenylacetic acid
      (DOPAC). Performance of the lever-pressing task resulted in significant increases
      in extracellular levels of DA and DOPAC relative to control rats. The increases
      in extracellular DA were significantly correlated (r = 0.92) with the number of
      lever press responses committed. In the second experiment, the neurotoxic agent 6
      hydroxydopamine was infused directly into the nucleus accumbens to investigate
      the effects of DA depletion on lever-pressing performance. DA depletion had only
      a modest effect on the total number of lever presses, and there was a significant
      effect on total lever presses only on the first test day (third day postsurgery).
      Analyses also were performed on responding across the 45-min session by breaking
      down the session into three 15-min periods. There was a significant group x time
      interaction, with DA-depleted rats showing a significant reduction in the numbers
      of responses in the first 15-min period, but no significant effects over the
      second or third 15 min in the session. This initial slowing of response rate was
      present across all 5 test days. These results indicate that DA release and
      metabolism increases in rats performing on a CRF schedule, and that DA depletion
      produces a slowing of initial response rate.

PMID- 8278436
TI  - Buprenorphine as a stimulus in drug discrimination learning: an assessment of mu
      and kappa receptor activity.
AB  - Using the conditioned taste aversion baseline of drug discrimination learning,
      different groups of animals were trained to discriminate either buprenorphine or
      morphine from distilled water. Specifically, animals were injected with
      buprenorphine or morphine prior to a saccharin-LiCl pairing and the drug vehicle
      prior to saccharin alone. By the fifth conditioning trial, animals differentially
      consumed saccharin on the basis of administration of the drug or its vehicle. In
      subsequent generalization tests, buprenorphine stimulus control generalized
      completely to the mu agonist morphine in four of the five subjects tested, while
      morphine stimulus control completely generalized to buprenorphine in two of five
      subjects and partially generalized in the remaining three. Buprenorphine failed
      to generalize to the relatively selective kappa antagonist MR2266 and the broad
      based antagonist diprenorphine. Morphine also failed to generalize to MR2266, but
      did generalize to diprenorphine. That morphine and buprenorphine displayed some
      degree of cross-generalization suggests that these compounds share some stimulus
      property, presumably their agonist activity at the mu receptor, and that the mu
      activity of these compounds was used in the establishment of the discrimination,
      a conclusion supported by the fact that compounds with mu antagonist activity
      (e.g., naloxone, MR2266) blocked both buprenorphine and morphine stimulus
      control. That buprenorphine failed to generalize to compounds with kappa
      antagonist activity suggests that animals trained to discriminate buprenorphine
      from its vehicle do not use the kappa antagonist activity of the drug in the
      establishment of the discrimination. The basis for the differential ability of
      various receptor subtypes to mediate the discriminative properties of compounds
      with mixed receptor activity was discussed.

PMID- 8278437
TI  - Effects of midazolam on the activity of phagocytosis in mice submitted to
      surgical stress.

PMID- 8278438
TI  - Periodic mother deprivation during the light period reversed the phase of
      serotonin N-acetyltransferase activity rhythm of the pineal gland in rat pups.
AB  - It has been reported that nursing mother rats can postnatally entrain the
      circadian rhythms of blinded rat pups, such as locomotor, drinking, and
      corticosterone rhythms. To gain more insight in the mechanism of the postnatal
      entrainment of such pups' circadian rhythms, we examined the serotonin N
      acetyltransferase (NAT) activity rhythm in blinded rat pups subjected to periodic
      mother deprivation (PMD) in which mothers were periodically deprived of their
      pups during either half of a day. We found that only PMD during the light period
      shifted the phase of NAT activity rhythm in the pups. To cause a reversal of the
      NAT activity rhythm, it was necessary to repeat PMD for more than 6 days. PMD for
      6 h each day also shifted the phase of the blinded rat pups, but it did not
      reverse the NAT rhythm, even when it was repeated for 10 days. In 9-h deprivation
      for 10 days, however, deprivation during the first 9 h of the light period
      reversed the phase, although the latter 9 h failed to cause reversal of the
      phase. On the other hand, restricted feeding of the mother took more than 11 days
      to reverse the phase and a foster mother in the cross-fostering experiment failed
      to affect the phase of pup's rhythm, when the rhythm was determined on the 11th
      postnatal day. These facts indicate that PMD during the light period is a potent
      entrainer of the pups' circadian NAT rhythms and provide a useful method of
      exploring the underlying mechanism of the entrainment of the pups' rhythm by the
      mother.

PMID- 8278439
TI  - Metabolic modulation by amino acid stimulation of the paraventricular nucleus of
      the hypothalamus.
AB  - The role of the paraventricular nucleus of the hypothalamus (PVN) in the
      regulation of energy expenditure and energy substrate utilization was
      investigated after the injection of the excitatory amino acid D,L-homocysteic
      acid (DLH) or its vehicle. Male Wistar rats with chronic PVN cannulae were tested
      for 1 h with no food available in an open-circuit calorimeter. Whereas low (0.5
      nmol), excitatory doses of DLH increased energy expenditure, the thermogenic
      effect became smaller and then vanished as the DLH dose was increased to
      inhibitory levels (7 and 50 nmol). None of these doses affected motor activity,
      indicating a primary thermogenic effect. The highest dose (100 nmol) increased
      energy expenditure, but this appeared to be secondary to increased locomotor
      activity. The increased locomotor activity produced by the highest dose of DLH
      constitutes the first demonstration of an activity effect induced by stimulating
      the PVN. However, this effect likely reflects the activation of neighboring
      areas. Only the 50 nmol dose of DLH increased respiratory quotient, indicating a
      shift toward the preferential utilization of carbohydrates as an energy
      substrate. These data complement our findings with neuropeptide Y and insulin in
      showing that different doses of the same substance injected into the PVN may
      produce qualitatively different effects. Furthermore, the present study
      demonstrates that exciting PVN neurons activates catabolic forces, whereas
      inhibiting them activates anabolic forces.

PMID- 8278440
TI  - Serotonin-2 receptors in the CNS of alcohol-preferring and -nonpreferring rats.
AB  - The densities of serotonin-2 (5-HT2) receptors, labelled with [3H]ketanserin
      (Ket), were examined in the CNS of alcohol-naive, adult, male alcohol-preferring
      (P) and -nonpreferring (NP) rats using quantitative autoradiography. The
      densities of binding sites labelled with 2.0 nM [3H]Ket were 15-25% lower (p <
      0.05) in layer IV of the medial prefrontal, frontal, cingulate, parietal, and
      temporal cortices of the P line compared with the NP line. [3H]Ket binding in the
      P rats was also 40-50% lower (p < 0.05) in the medial and lateral nucleus
      accumbens, olfactory tubercle, and caudate-putamen, and 20% lower (p < 0.05) in
      the claustrum, compared with the NP line. No differences in 2.0 nM [3H]Ket
      binding were observed between the lines in the piriform cortex, hypothalamus,
      amygdala, hippocampus, ventral tegmental area, substantia nigra, central gray,
      and interpenduncular nucleus. Scatchard analysis of [3H]Ket binding (0.5-0.6 nM,
      determined in layer IV of the frontal and parietal cortex and in the lateral
      nucleus accumbens, indicated lower Bmax values without a change in Kd for the P
      compared to the NP rats. The results of this study indicate that there are fewer
      5-HT2 receptors in certain CNS regions of the P relative to the NP rats.

PMID- 8278441
TI  - Sex differences in amphetamine-induced locomotor activity in adult rats: role of
      testosterone exposure in the neonatal period.
AB  - The present studies assessed the extent to which adult sex differences in
      responsiveness to both acute and repeated amphetamine (AMPH) treatment can be
      attributed to differential exposure to testosterone (T) during the early critical
      period for sexual differentiation. At birth, male pups were sham-operated or
      gonadectomized, whereas female pups were given T or an oil injection. In
      adulthood, all animals were gonadectomized or sham-operated. Locomotor activity
      in response to either 1.5 mg/kg AMPH (IP) or the saline vehicle was measured for
      2 h every third day, on five occasions. On the sixth occasion, all animals
      received 0.75 mg/kg AMPH (IP) in a test for sensitization. In Experiment 1,
      animals were tested in the absence of circulating gonadal hormones, whereas in
      Experiment 2, all animals received 5.0 micrograms estradiol benzoate (SC), 30-35
      min prior to each behavioral test. Results indicate that neonatal exposure to T
      suppresses responsiveness to AMPH in adulthood. The differences between neonatal
      T-exposure groups were magnified in the presence of circulating estradiol. The
      fact that female animals were more responsive to AMPH regardless of neonatal T
      exposure suggests that lifetime exposure to estradiol alters responsiveness to
      this hormone, and to AMPH, in adult animals and/or that exposure to T both pre-
      and postnatally is necessary for the full suppression of responsiveness seen in
      adult male animals.

PMID- 8278442
TI  - Long-term treatment of obese Zucker rats with LY255582 and other appetite
      suppressants.
AB  - LY255582, administered subcutaneously, decreased food intake and body weight gain
      of fed obese Zucker rats during the entire 30-day period of treatment. No
      tolerance to these biologic effects of LY255582 could be demonstrated. d
      Amphetamine and naltrexone, administered subcutaneously, and d,l-fenfluramine and
      salbutamol, administered orally, decreased food intake for no more than 6 to 12
      days, in contrast to the long-lasting effects of LY255582. Salbutamol suppressed
      the appetite of obese rats for 3-4 days only. After an additional 12 days of
      treatment, weight gain decreased significantly accompanied by no appetite
      suppression. Thus, there is a difference in the duration of action of the opioid
      antagonist, LY255582, when compared to amphetamine, fenfluramine, naltrexone, and
      salbutamol, on food intake and body weight gain of obese rats.

PMID- 8278444
TI  - Evaluation of depression in rats exposed to chronic (unpredictable) electric
      shock.
AB  - The present study was undertaken to evaluate the applicability of a proposed
      behavioral stress paradigm as an animal model for depression. Rats were trained
      to press a lever under a fixed ratio (FR) 5 schedule in a Skinner box for 10 days
      and were subsequently exposed to a daily regimen of 20 cycles of FR 5 and 10
      cycles of variable ratio (VR) 10 for about a week. This exposure resulted in a
      reduction of the number of lever presses and successful escapes compared to the
      level achieved after training. In addition, weight gain was significantly
      suppressed compared with other treatments. Acute and chronic administration of
      psychotropic drugs (imipramine and chlordiazepoxide) showed that treatment with
      imipramine increased both the number of lever presses and successful escapes
      while chlordiazepoxide increased only the number of lever presses. The results
      suggest that this simplified animal model utilizing chronic unpredictable
      electric shock may be useful in the study of human depression.

PMID- 8278443
TI  - Pentobarbital, diazepam, and ethanol abolish the interphase diminution of pain in
      the formalin test: evidence for pain modulation by GABAA receptors.
AB  - There are two phases to the behavioral response to injection of formalin. After
      an initial vigorous response, a period of reduced pain occurs 10 to 15 min after
      formalin, followed by reemergence of pain-related behaviors. These phases are
      believed to represent acute chemical stimulation of afferent neurons followed by
      injury-related inflammatory pain. Pentobarbital (10, 15, or 25 mg/kg), diazepam
      (0.5, 1.5, or 5.0 mg/kg), or ethanol (0.5, 1.0, or 1.5 g/kg) attenuated the
      diminution of pain between the two phases, so that pain was continuous throughout
      60 min of testing, but had no effect on pain scores during the peaks of either
      phase. The effects of pentobarbital and diazepam were blocked by picrotoxin (2.5
      mg/kg), which itself had no effect. Ro 15-1788 also blocked the effect of
      diazepam. Picrotoxin did not effectively antagonize the effect of ethanol. A high
      dose of picrotoxin (5.0 mg/kg) caused seizures in some rats and also eliminated
      the interphase depression of pain. The results suggest that the biphasic time
      course of formalin pain is produced by a central antinociceptive mechanism that
      is inhibited by GABAA receptors.

PMID- 8278445
TI  - Behavioral effects of a LHRH antagonist in intact and ovariectomized rats.
AB  - The effects of the LHRH antagonism on the acquisition of conditioned responses
      (CARs) and spontaneous motility were studied in intact and ovariectomized rats. A
      synthetic antagonist of LHRH, [N-acetyl-D-p-chloro-Phe1,2,D-Trp3,D-Arg6,D-Ala10]
      LHRH, was injected in a single dose (10 micrograms/rat, SC) at noon on the day of
      proestrus in the normally cycling rat, and behavioral experiments were carried
      out on the morning of estrus or metestrus. Two procedures were followed in the
      ovariectomized rats: in the first, the antagonist was injected 1 h before
      estradiol, and in the second, at noon on the day after estradiol replacement. The
      experiments were carried out 24 and 48 h after estradiol, respectively. The LHRH
      antagonist facilitated the acquisition of CARs in both experimental groups, thus
      reversing the impairments observed during estrus and metestrus and those induced
      by estradiol replacement. The antagonist decreased the number of head shakes
      during estrus, whereas it induced an increase in total motility and rears in
      ovariectomized control animals. On the other hand, the antagonist increased the
      number of rears and reversed the decrease in grooming behavior induced by
      estradiol. The results led to the idea of a role of LHRH in behaviors not
      apparently related to sex, which could explain the behavioral changes observed
      across the estrous cycle and those induced by estradiol replacement in
      ovariectomized rats.

PMID- 8278446
TI  - Precipitated abstinence in the diazepam-dependent rat.
AB  - Physical dependence was produced in the rat by exposure to continuous release of
      diazepam from silastic capsule implants (recrystallized diazepam) or by dosing
      through a gastric fistula. The precipitated abstinence syndrome induced by the IV
      infusion of flumazenil was characterized by clonic and tonic-clonic seizures,
      retropulsion, digging, rearing, head, limb and body tremors, twitches and jerks
      of the body, and ear twitches. This abstinence syndrome differed both
      qualitatively and quantitatively from the milder syndrome induced in previous
      experiments by the intragastric administration of flumazenil in the diazepam
      dependent gastric fistula rat. Capsule-implanted rats had free plasma and
      extraneuronal brain levels of diazepam, oxazepam, and nordiazepam in the 10(-3)
      and 10(-4) mg/ml range, and their brain: plasma ratios were not significantly
      different from 1. The diazepam capsules had a sustained release of over 28 days.
      These studies show that the capsule implantation technique is an efficacious way
      of maintaining plasma levels of diazepam and its metabolites, and producing a
      high level of physical dependence in the rat.

PMID- 8278447
TI  - Pertussis toxin attenuates intracranial morphine self-administration.
AB  - Mu and delta opioid receptor subtypes are thought to mediate the reinforcing
      actions of opioids. Since these opioid receptors use pertussis toxin (PTX)
      sensitive inhibitory G-proteins for signal transduction, we determined whether
      PTX would block the opioid reinforcement signals produced by intrahippocampal or
      intraventral tegmental area (VTA) injections of morphine in rats. Hippocampal PTX
      pretreatment prevented the acquisition of intrahippocampal morphine self
      administration. Similarly, in rats previously trained to self-administer morphine
      in the VTA, PTX injections in the VTA abolished morphine self-administration
      behavior, while sparing behavior reinforced by food pellets. This result
      suggested that the toxin did not interfere generally with motor capacity but
      rather acted selectively to block morphine reinforcement. Inactivated PTX did not
      reduce VTA morphine self-administration, thus demonstrating that PTX blockade of
      opioid reinforcement is primarily due to enzymatic inactivation of inhibitory G
      proteins. All these findings are consistent with the hypothesis that inhibitory G
      proteins in the hippocampus and VTA mediate the reinforcing effects of opioid
      drugs.

PMID- 8278448
TI  - Ca2+/calmodulin system: participation on rat sexual hypothalamic differentiation.
AB  - Modifications of male rat hypothalamic sexual differentiation after neonatal
      administration of drugs that participate on the Ca2+/calmodulin system
      (haloperidol, trifluoperazine, penfluridol, pimozide, and verapamil) were
      studied. Pups treated 72 h after birth were behaviorally tested on day 120 of
      extrauterine life. Five tests for homotypical behavior were conducted. Afterwards
      animals were castrated and tested twice for heterotypical (female) behavior under
      replacement hormonal therapy. Fifty percent (80% in the case of pimozide) of all
      treated males showed lordotic behavior compared with none of the controls.
      Haloperidol (39%, lordosis quotient) and pimozide (40%, lordosis quotient) were
      more active than the others. Results obtained with verapamil were not
      statistically different from the controls. Pimozide was the most active agent
      influencing the appetitive masculine behavior (mount latency, intromission
      latency, and postejaculatory interval). Verapamil was more efficient than the
      rest of the drugs on the consummatory behavior (mount latency, intromission
      frequency, interintromission interval, and ejaculatory latency). Our results
      support the participation of the Ca2+/calmodulin system in hypothalamic sexual
      differentiation and in the differential modulation of the masculine and feminine
      behavioral patterns.

PMID- 8278449
TI  - Further proof that (-)deprenyl fails to facilitate mesolimbic dopaminergic
      activity.
AB  - The selective monaminooxidase (MAO)-B inhibitor (-)deprenyl facilitates the
      nigrostriatal dopamine (DA)-ergic system by a complex mechanism that includes
      inhibition of DA reuptake and increase of DA turnover. In this study, DA reuptake
      and DA turnover were measured in the olfactory tubercle of rats treated with 0.25
      mg/kg (-)deprenyl for 28 days. There was no difference between these rats and the
      saline-treated group. In another series of experiments, we analysed how (
      )deprenyl influences the action of some indirectly acting DA agonists, such as
      amphetamine (AM) and phenylethylamine (PEA). The effect on different behavioural
      patterns related either to the nigrostriatal (stereotyped behaviour) or the
      mesolimbic (rearing, locomotion) DAergic system was investigated. As expected,
      the PEA-induced stereotyped behaviour was tremendously potentiated by (-)deprenyl
      and the AM-induced stereotypy was reduced. At the same time there was no change
      in locomotion and rearing. The results give further biochemical and behavioural
      proof that (-)deprenyl enhances the function of the nigrostriatal DAergic system
      and leaves the mesolimbic DAergic neurons unaffected.

PMID- 8278450
TI  - Real time detection of acute (IP) cocaine-enhanced dopamine and serotonin release
      in ventrolateral nucleus accumbens of the behaving Norway rat.
AB  - Cocaine (10 mg/kg), administered intraperitoneal (IP), was studied for its
      effects on dopamine (DA) and serotonin (5-HT) release in ventrolateral nucleus
      accumbens (vlNAcc) of conscious and behaving male, virus-free, Sprague-Dawley
      rats with in vivo electrochemistry (voltammetry). Miniature stearate probes
      detected DA and 5-HT release, on line and within a temporal resolution of
      seconds. Psychostimulant behaviors, in the form of four behavioral components
      (i.e., the classically DA-dependent behaviors of locomotor activity
      [ambulations], rearing, and stereotypy, and a 5-HT-ergic behavior, central
      ambulations) were studied concurrently with infrared photobeam detection. The
      results show that (IP) cocaine significantly increased vlNAcc DA release (p <
      0.0001) and 5-HT release (p < 0.0012). Each of the four parameters of cocaine
      induced psychostimulant behavior was concurrently and significantly increased as
      well (ambulations: p < 0.0001); rearing p < 0.0008; stereotypy: p < 0.0004;
      central ambulations: p < 0.0082). Moreover, exactly coincident data points for DA
      and 5-HT release occurred 10 and 40 min after (IP) cocaine administration.
      Cocaine-induced DA and 5-HT release were highly and positively correlated during
      the first hour of study (p < 0.01). As expected, increased DA release in vlNAcc
      after cocaine administration was significantly and positively correlated with
      classically DA-dependent behaviors (first- and second-hour effects) (p < 0.01)
      and with the 5-HT-ergic behavior, central ambulations (p < 0.01). Also, cocaine
      induced 5-HT release was significantly and positively correlated with 5-HT
      behavior (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278451
TI  - Housing conditions alter GABAA receptor of alcohol-preferring and -nonpreferring
      rats.
AB  - The effects of housing conditions on some functional properties of the GABAA
      benzodiazepine (BZD) receptor in the cerebral cortex were examined in the
      selectively bred alcohol-preferring (P) and -nonpreferring (NP) lines of rats.
      Compared to rats housed in pairs (P with P and NP with NP), P and NP rats housed
      individually had 44% (p < 0.005) and 32% (p < 0.01) lower values, respectively,
      for GABA-stimulated 36Cl- influx into cortical microsacs. The maximal effect
      (Vmax) of flunitrazepam (FNZ) to enhance GABA-stimulated 36Cl- uptake was 44%
      higher in individually housed P rats than pair-housed P rats (p < 0.05) and 51%
      higher than individually housed NP rats (p < 0.05). There was no difference
      between single and pair-housed NP rats for Vmax values of FNZ enhancement of GABA
      stimulated 36Cl- influx. The results show housing conditions can alter some of
      the functional properties of the GABAA/BZD receptor in the P and NP lines of
      rats. The differential effect of housing conditions on FNZ enhancement of 36Cl-
      influx, observed between the lines, may be a result of higher levels of anxiety
      being produced by brief isolation in the P rat.

PMID- 8278452
TI  - Triiodothyronine (T3) modifies cholinergic-induced hypothermia and tremor in
      rats.
AB  - Hypothermia and tremor responses of oxotremorine and eserine were studied in rats
      after several T3 treatment regimens. The T3 antagonized oxotremorine-induced
      hypothermia and failed to antagonize eserine hypothermic effect, but potentiated
      oxotremorine- and eserine-induced tremors. Acetylcholinesterase activity was not
      altered in T3 rats. The hypothetical mechanisms to explain changes of central
      cholinergic responses caused by T3 are discussed.

PMID- 8278453
TI  - Acute effects of caffeine on several operant behaviors in rhesus monkeys.
AB  - The acute effects of 1,3-trimethylxanthine (caffeine) were assessed using an
      operant test battery (OTB) of complex food-reinforced tasks that are thought to
      depend upon relatively specific brain functions, such as motivation to work for
      food (progressive ratio, PR), learning (incremental repeated acquisition, IRA),
      color and position discrimination (conditioned position responding, CPR), time
      estimation (temporal response differentiation, TRD), and short-term memory and
      attention (delayed matching-to-sample, DMTS). Endpoints included response rates
      (RR), accuracies (ACC), and percent task completed (PTC). Caffeine sulfate (0.175
      20.0 mg/kg, IV), given 15 min pretesting, produced significant dose-dependent
      decreases in TRD percent task completed and accuracy at doses > or = 5.6 mg/kg.
      Caffeine produced no systematic effects on either DMTS or PR responding, but low
      doses tended to enhance performance in both IRA and CPR tasks. Thus, in monkeys,
      performance of an operant task designed to model time estimation is more
      sensitive to the disruptive effects of caffeine than is performance of the other
      tasks in the OTB.

PMID- 8278454
TI  - Detection of a neurotoxic quaternary pyridinium metabolite in the liver of
      haloperidol-treated rats.
AB  - Various theories have been proposed in the past to explain the side effects
      associated with haloperidol treatment. In this study, we tested the hypothesis
      that in vivo biotransformation of haloperidol to a quaternary pyridinium
      metabolite might contribute to some of these effects. Administration of
      haloperidol (IP or by gavage) to male Wistar rats results in its
      biotransformation to a butyrophenone quaternary pyridinium metabolite similar to
      MPTP metabolism to MPP+. The corresponding methyl quaternary pyridinium compound
      was not detected in the liver or brain of the rats used in this study. The
      proposed methyl quaternary pyridinium compound and the observed butyrophenone
      metabolite were tested for neurotoxicity in a frog model of MPTP action and were
      found to have neurotoxic effects, although the methyl quaternary pyridinium
      compound was much more toxic.

PMID- 8278455
TI  - Morphine enhances hedonic taste palatability in rats.
AB  - The question of whether opiates stimulate feeding by enhancing taste pleasure was
      investigated by examining the effect of morphine upon hedonic and aversive
      reactions to taste (tongue protrusions, gapes, etc.). Rats (n = 12) were given SC
      injections of morphine (4 mg/kg) or equal volumes of isotonic saline 2 h after
      the start of their daily light cycle. Food intake was measured in a 2-h test. On
      days when they were given morphine, rats ate significantly more food than when
      given saline. Hedonic and aversive taste reactions were elicited by an infusion
      of sucrose-quinine solution into the mouth and were measured subsequently in a
      slow-motion video analysis. The same rats that showed an increase in food intake
      after treatment with morphine showed a significant increase in their positive
      hedonic responses. Aversive reactions were unchanged by morphine. The results
      support the hypothesis that morphine enhances feeding by increasing the hedonic
      palatability of food.

PMID- 8278456
TI  - Effects of benzodiazepine agonist, antagonist and inverse agonist on ethanol
      induced changes in beta-endorphin levels in specific rat brain regions.
AB  - The present study was conducted to evaluate and compare effects of the
      benzodiazepine agonist diazepam, antagonist flumazenil and inverse agonist RO 15
      4513 on ethanol-induced changes in beta-endorphin (beta-EN) levels in specific
      rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour
      light:12-hour dark illumination cycle were used in this study. Ethanol (3 g/kg as
      22.5% solution in saline), flumazenil (10 mg/kg), RO 15-4513 (10 mg/kg), diazepam
      (2 mg/kg) or a combination of ethanol (3 g/kg) and flumazenil (10 mg/kg), RO 15
      4513 (10 mg/kg) or diazepam (2 mg/kg) were administered intraperitoneally to rats
      at 7.00 h. Control animals were injected with saline. Animals were sacrificed by
      decapitation 1 h after injection; the brains were immediately removed; the
      cortex, hippocampus and hypothalamus were dissected and their beta-EN levels
      measured by radioimmunoassay. Ethanol administration significantly increased beta
      EN levels in the hippocampus and hypothalamus but had no effect on beta-EN levels
      in the cortex. Similar increases in beta-EN levels in the hippocampus and
      hypothalamus also occurred following either flumazenil or diazepam. On the other
      hand, RO 15-4513 significantly increased beta-EN levels in the cortex and
      hypothalamus. When flumazenil was concurrently administered with ethanol, it
      completely reversed the ethanol effects in the hippocampus but failed to do so in
      the hypothalamus. Concurrent administration of RO 15-4513 with ethanol also
      reversed the ethanol-induced rise of beta-EN in the hypothalamus. However,
      concurrent administration of diazepam and ethanol did not block the increase in
      beta-EN levels.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278457
TI  - Dizocilpine (MK-801) blocks tolerance to the analgesic but not to the
      hyperthermic effect of morphine in the rat.
AB  - The effect of dizocilpine (MK-801), an N-methyl-D-aspartate receptor antagonist,
      on the development of tolerance to the analgesic and hyperthermic effects of
      morphine was determined in the rat. Tolerance to morphine in male Sprague-Dawley
      rats was induced by implanting subcutaneously 6 morphine pellets during a 7-day
      period. Two schedules of intraperitoneal injections of MK-801 were used. In one,
      the drug was injected once a day, and in the other it was injected twice a day.
      The doses of MK-801 were 0.03, 0.1 and 0.3 mg/kg. In the treatment once a day, MK
      801 blocked the development of tolerance to the analgesic effect of morphine, but
      there was no dose-dependent effect. In the treatment twice a day, MK-801 produced
      a dose-dependent inhibition of tolerance to the analgesic effect of morphine.
      Higher doses of MK-801 produced high mortality. MK-801 given once a day or twice
      a day failed to affect the tolerance to the hyperthermic effect of morphine. In
      both schedules of MK-801 treatment, the highest dose of MK-801 resulted in high
      mortality. It is concluded that MK-801 is selective in blocking the tolerance to
      the analgesic effect of morphine in the rat.

PMID- 8278458
TI  - Effect of blockade of the ATP-sensitive potassium channel on metabolic coronary
      vasodilation in the dog.
AB  - The hypothesis that the ATP-sensitive potassium channel provides the link between
      change in coronary blood flow and myocardial oxygen demand was tested in 9 dogs
      instrumented to measure coronary flow and regional wall thickening in the basal
      state and at a high level of myocardial oxygen consumption produced by systemic
      infusion of phenylephrine and simultaneous atrial pacing at an elevated heart
      rate. Measurements were recorded before and after blockade of ATP-sensitive
      potassium channels with intracoronary glibenclamide (2 mumol/min). While
      glibenclamide reduced the absolute level of coronary flow in the basal state, the
      increase in flow due to increased metabolic demand was unchanged compared with
      control. Thus, activity of the ATP-sensitive potassium channel determines the set
      point from which adjustments of coronary flow in response to metabolic stimuli
      occur, but does not provide a link between changes in oxygen demand and changes
      in coronary flow.

PMID- 8278459
TI  - ICI 206,970: a novel calcium channel blocker with eukalemic diuretic activity.
AB  - ICI 206,970 is a novel eukalemic diuretic from the aminomethylphenol pyrazine
      series which exhibited a calcium antagonist profile. The isolated rat aorta
      evaluation and dihydropyridine ligand [3H]-PN 200-110 binding studies
      demonstrated that ICI 206,970, like verapamil and nifedipine, inhibits vascular
      smooth muscle tone by inhibiting voltage-sensitive calcium channels. ICI 206,970
      produced dose-related hypotensive, negative chronotropic, dromotropic, and
      coronary vasodilator responses after i.v. injection in anesthetized dogs. ICI
      206,970, similar to calcium channel blockers and dissimilar to diuretics,
      produced an acute antihypertensive effect in spontaneously hypertensive rats
      (SHR), and significant protection against the development of myocardial
      hypertrophy in SHR after chronic oral treatment for 28 consecutive days. It is
      concluded that ICI 206,970 is a calcium channel blocker in addition to its novel
      eukalemic diuretic property.

PMID- 8278460
TI  - Effect of acute and chronic moderate hypoxia on diltiazem kinetics and metabolism
      in the dog.
AB  - The aim of this study was to assess whether moderate hypoxia affects the
      disposition of diltiazem. Six male beagle dogs received diltiazem (0.6 mg/kg) on
      three occasions: (1) while breathing air, i.e. during normoxia; (2) 1 h after
      initiating exposure to a FiO2 of 0.08, a FiCO2 of 0.035 and a FiN2 of 0.885, i.e.
      during acute hypoxia and normocapnia, and (3) during chronic hypoxia, i.e. after
      120 h of exposure to a FiO2 of 0.08. Multiple blood samples were withdrawn and
      urine was collected to assay diltiazem and metabolites [N-desmethyl diltiazem
      (MA), deacetyl diltiazem (DAD) and N-desmethyl deacetyl diltiazem (M2)].
      Breathing air, mean arterial partial pressure of oxygen was 83.2 +/- 3.2; during
      acute hypoxia 42.2 +/- 0.7; and during chronic hypoxia, 41.9 +/- 0.6 mm Hg. Acute
      hypoxia did not alter diltiazem disposition. Compared to dogs with normoxia,
      chronic hypoxia reduced diltiazem metabolic clearance, from 64 +/- 3 to 51 +/- 5
      ml/min/kg (p < 0.05), as well as its volume of distribution, from 11.4 +/- 1.2 to
      9.1 +/- 0.3 liters/kg (p < 0.05). Chronic hypoxia decreased the fraction of
      diltiazem metabolic clearance, normalized by the glomerular filtration rate,
      generating the M2 metabolite, although this experimental condition did not affect
      the formation of MA or DAD. It is concluded that chronic moderate hypoxia reduced
      diltiazem systemic clearance because it decreased selected pathways of
      biotransformation.

PMID- 8278461
TI  - Methionine adenosyltransferase: structure and function.
AB  - Methionine adenosyltransferase (MAT), a key enzyme in metabolism, catalyzes the
      synthesis of one of the most important and pivotal biological molecules, S
      adenosyl-methionine. In every organism studied thus far, MAT exists in multiple
      forms; most are encoded by related, but distinct genes. Molecular and
      immunological studies revealed the presence of considerable conservation in the
      structure of MAT from different species; however, the various MAT isozymes differ
      in their physical and kinetic properties in ways that allow them to be regulated
      differently. Recent studies suggest that human MAT is composed of nonidentical
      subunits that can assume multiple states of aggregation, each with different
      kinetic characteristics. The tissue distribution of MAT isozymes and the ability
      of cells within the same tissue to switch between the different forms of MAT
      suggest that this mode of regulation is important for cellular function and
      differentiation. Therefore, understanding the regulation and structure-function
      relationship of this fascinating enzyme should help us clarify its role in
      biology and may provide us with tools to effectively manipulate its activity in
      clinical situations such as cancer, autoimmunity and organ transplantation.

PMID- 8278462
TI  - Podophyllotoxin, steganacin and combretastatin: natural products that bind at the
      colchicine site of tubulin.
AB  - A large number of antimicrotubule agents are known that bind to tubulin in vitro
      and disrupt microtubule assembly in vitro and in vivo. Many of these agents bind
      to the same site on the tubulin molecule, as does colchicine. Of these, the
      natural products podophyllotoxin, steganacin and combretastatin are the subjects
      of this review. For each of these, the chemistry and biochemistry are described.
      Particular attention is given to stereochemical considerations. Biosynthetic
      pathways for podophyllotoxin and congeners are surveyed. The binding to tubulin
      and the effects on microtubule assembly and disassembly are described and
      compared. In addition, structural features important to binding are examined
      using available analogs. Several features significant for tubulin interaction are
      common to these compounds and to colchicine. These are described and the
      implications for tubulin structure are discussed. The manifold results of
      applying these agents to biological systems are reviewed. These actions include
      effects that are clearly microtubule mediated and others in which the microtubule
      role is less obvious. Activity of some of these compounds due to inhibition of
      DNA topoisomerase is discussed. The range of species in which these compounds
      occur is examined and in the case of podophyllotoxin is found to be quite broad.
      In addition, the range of species that are sensitive to the effects of these
      compounds is discussed.

PMID- 8278463
TI  - The effect of carbon dioxide on cerebral arteries.
AB  - The constancy of cerebral blood flow and volume relies heavily upon the cerebral
      arteries' intrinsic ability to respond to changes in the partial pressure of
      arterial CO2. The physiologic mechanisms underlying these responses have not been
      determined, although changes in extracellular and intracellular pH, mediation by
      prostanoids and neural activity have been suggested. CO2 reactivity can be
      influenced by oxygen status and blood pressure and can vary according to age and
      brain region. In certain pathological conditions or diseases, it can be severely
      altered. Modern techniques, which measure CBF in cases of cerebral hemodynamic
      insufficiency, head injury or tumor, rely on the inherent ability of the cerebral
      circulation to respond to changing levels of CO2.

PMID- 8278464
TI  - The effects of rigid fixation on craniofacial growth of rhesus monkeys.
AB  - A male infant rhesus monkey model was used to examine the growth effect on the
      craniofacial skeleton caused by osteotomy and three types of fixation:
      interfragmentary wiring, microplate and screw fixation, and "extensive"
      microplate and screw fixation. The animals (n = 12) were allowed to mature until
      cranial growth was at least 95 percent complete. Direct craniometric measurements
      were obtained and analyzed for differences in the three treated groups. A group
      of unoperated male animal skulls also was analyzed as controls (n = 5). A subtle
      visible and measurable restriction of growth in the operated area occurred in all
      treatment groups. Significant differences (p < 0.05) were found in only 4 of the
      39 craniometric chords measured. Interfragmentary wiring showed fewer growth
      restrictive effects than standard use of microfixation plates. Extensive use of
      rigid fixation devices caused the greatest degree of growth disturbance.
      Osteotomy and fixation in the infant rhesus monkey affect craniofacial growth,
      with the degree of growth restriction increasing with the amount of fixation
      hardware.

PMID- 8278465
TI  - Retrograde microvascular augmentation (turbocharging) of a single-pedicle TRAM
      flap through a deep inferior epigastric arterial and venous loop.
AB  - Modern trends in breast reconstruction with the TRAM flap have promoted adequate
      blood supply to the flap while minimizing the donor-site defect in the anterior
      abdominal wall. Preservation of the rectus abdominis muscle (both unipedicled and
      bipedicled), supercharging, delayed, and free-flap techniques all have promoted
      these principles. A new technique is presented utilizing the single pedicle with
      a transmidline retrograde microvascular loop anastomosis of the deep inferior
      epigastric artery and vein. The turbocharging allows increased blood flow to the
      remote areas of the flap as well as augmented venous outflow. In addition, the
      abdominal-wall donor site is similar to that of a single pedicle. This technique
      is ideal for reconstruction where the entire flap is required, a lower abdominal
      scar is present, or the recipient vessels for the free flap are absent or
      damaged.

PMID- 8278466
TI  - Experience with 326 inflatable breast implants.
AB  - Inflatable breast implants, which have been available for 27 years, have been
      accepted with varying enthusiasm. Advocates suggest that they result in breasts
      that look and feel natural because they have a low incidence of capsular
      contracture. Others note the obvious: Anything that is inflated may deflate. The
      purposes of this report are to present our experience with inflatable breast
      implants and to focus on deflation. We examined the records of all our patients
      who underwent breast augmentation or reconstruction. The 173 patients who had 326
      inflatable breast implants form the basis of this report. Eighty-four percent of
      the patients were treated for aesthetic reasons; 16 percent were for
      reconstruction after mastectomy. The longest follow-up was 14.5 years, and the
      shortest was 3 months. Our findings indicate that inflatable breast implants
      remain soft. Overall, 256 implants (78.5 percent) were Baker I, 39 (12.0 percent)
      were Baker II, 28 (8.6 percent) were Baker III, and 3 (0.9 percent) were Baker
      IV. Twenty (6.1 percent) of the 326 implants deflated. No patient whose implant
      deflated had a closed capsulotomy nor gave a history of a proximate athletic
      endeavor. Most deflations were associated with pain, not previously present, and
      over the next few days the patient noted that her breast became smaller. All
      deflations were explored surgically, usually within 1 week. At surgery, a white
      fold was noted usually where the leak in the implant occurred. It was easy to
      slide out the old implant and insert a new one. The shortest interval between the
      surgery and deflation was 3 months; the longest was 9 years and 9 months.

PMID- 8278467
TI  - The effect of Siltex texturing and povidone-iodine irrigation on capsular
      contracture around saline inflatable breast implants.
AB  - A prospective, controlled, and blinded clinical study was performed on 56 patient
      volunteers to determine the effects of two independent variables--the Siltex
      textured inflatable implant and povidone-iodine irrigation--on the incidence of
      fibrous capsular contracture following retromammary augmentation. Each patient
      was randomly assigned both textured and smooth implants and povidone-iodine and
      saline irrigation, so that each patient served as her own control. The Siltex
      devices experienced an incidence of class III-IV contracture of only 2 percent,
      as compared with an incidence of 40 percent around the smooth devices. Most
      patients, however, preferred the smooth devices despite the higher contracture
      incidence because the Siltex device was more easily palpable. Povidone-iodine did
      not reduce the final incidence of contracture. It appeared to delay the onset of
      contracture, but not with statistical significance.

PMID- 8278468
TI  - Treatment of vaginal agenesis with vulvoperineal fasciocutaneous flaps.
AB  - A simple surgical technique is reported for the treatment of vaginal agenesis
      utilizing vulvoperineal fasciocutaneous flaps based on the terminal vessels of
      the internal pudendal artery. Two vulvoperineal axial flaps are sutured together,
      skin surface opposed, then rotated posteriorly into rectovesical space. The
      operation has been performed on one patient, with good anatomic and functional
      results and without complications.

PMID- 8278469
TI  - Reassessment of surgery for mallet finger.
AB  - For fresh mallet finger with terminal tendon rupture, conservative treatment is
      the method chosen by many hand surgeons. However, long-term splinting is
      troublesome and also tends to cause an extension deficit or impaired flexion of
      the distal interphalangeal joint. In this article, the surgical treatment of
      fresh mallet finger is discussed as an alternative to conservative splinting.
      Fifteen patients underwent surgical intervention with a wire implant combined
      with mobilization in the early postoperative period. By 1 year after surgery, the
      mean extension deficit was reduced to 6 degrees, and an improvement of 34 degrees
      was observed. The active range of motion of the distal interphalangeal joint
      reached 58 degrees, which was 65.8 percent of that on the unaffected side. These
      surgically treated patients expressed greater satisfaction with the outcome than
      did a conservatively treated group. We concluded that for patients to whom fine
      manual dexterity is important, surgery is a better option than conservative
      therapy in treating fresh mallet finger.

PMID- 8278470
TI  - Implantable venous Doppler microvascular monitoring: laboratory investigation and
      clinical results.
AB  - The purpose of this study was to compare the sensitivity of a 20-mHz ultrasonic
      Doppler device to detect microvascular thrombosis placed on the vein with that
      placed on the artery. A feasibility study in animals preceded a comparative
      clinical study in patients. Six rabbits were used to develop a bilateral hind
      limb perfusion model. The femoral artery and vein were isolated, and Doppler
      probes were affixed to each. Clamping of the artery and vein separately was
      followed by simultaneous measurements in both vascular probes using audio signals
      and strip-chart recordings. A total of 48 measurements were obtained. Probes
      placed on the artery immediately detected an arterial occlusion but continued to
      record pulsation for 220 +/- 40 minutes following venous occlusion. Mean arterial
      waveform amplitudes diminished by 50 percent of initial values 1 hour following
      venous occlusion but showed little change thereafter when followed for 6 hours.
      By contrast, probes placed on the vein detected venous occlusion immediately and
      arterial occlusion at 6 +/- 2.4 minutes (p < 0.001). Over a 4-year period, 133
      patients had free-tissue transfers monitored by implantable 20-mHz ultrasonic
      Doppler devices: 30 arterial and 103 venous. The arterial monitors detected
      vascular thromboses in 4 of 6 patients, with 3 flaps salvaged. Venous Doppler
      monitors detected 16 of 16 thromboses, with 12 flaps salvaged. Six patients had
      probe/machine malfunctions during their postoperative course and were monitored
      by clinical means thereafter without thrombosis. There were two late extrusions
      of the probe cuffs implanted in subcutaneous locations. No adverse effects on the
      flap vessels were noted in the study. The 20-mHz ultrasonic Doppler device is an
      effective monitor of blood flow in microvascular anastomoses. When it is placed
      on the vein, a greater degree of sensitivity is demonstrated, particularly to
      venous obstruction, compared with probes monitoring arterial flow. The device has
      been reliable in a variety of institutions and nursing units without need for
      intensive care monitoring and has resulted in an increased salvage rate for flaps
      experiencing vascular thrombosis.

PMID- 8278471
TI  - Metopic synostosis: quantitative assessment of presenting deformity and surgical
      results based on CT scans.
AB  - Our study applied a method of using 14 clinically relevant measurements of CT
      scan images to document skeletal dysmorphology in patients with metopic
      synostosis to determine the effectiveness of their surgical procedure after a
      minimum of 1 year. Ten consecutive patients with metopic synostosis who underwent
      a standard surgical procedure were reviewed. Preoperative and postoperative (> 1
      year) CT scans were compared with those of age-matched controls. Percentages of
      normal were then compared for significant differences. Preoperative cranial vault
      measurements revealed a narrowed anterior intercoronal distance at 92 percent of
      normal. Orbital measurements showed a narrowed anteromedial wall interorbital
      distance at 79 percent of normal, a narrowed lateral orbital wall distance at 94
      percent, and an elevated medial orbital wall protrusion beyond the plane of the
      lateral orbital walls at 115 percent. After surgery, the intercoronal distance
      was significantly corrected to 101 percent, the anteromedial wall interorbital
      distance was improved but remained undercorrected at 90 percent, and the medial
      wall protrusion was significantly decreased to 98 percent of normal. Quantitative
      measurements of CT scan images confirmed clinically observed physical findings in
      unoperated trigonocephaly to be orbital hypotelorism, retruded lateral orbital
      rims, and a narrowed bitemporal width. The surgical technique corrected the
      lateral orbital wall aspects of the deformity as well as the narrowed anterior
      cranial vault width and improved the orbital hypotelorism.

PMID- 8278472
TI  - Distraction osteogenesis in the irradiated canine mandible.
AB  - The potential use of distraction osteogenesis in mandibular reconstruction has
      been limited by its questionable efficacy in previously radiated bone. We studied
      five mongrel dogs that had a hemimandible rendered edentulous and underwent a
      full course of external beam radiation therapy (50 Gy/20 fractions). Six months
      after completion of radiotherapy, a 2-cm critical-size segmental mandibular
      defect was created and stabilized with a stainless steel plate. A proximal
      mandibular transport segment was then formed and an external lengthening
      apparatus (Orthofix) applied. By means of bifocal distraction osteogenesis, the
      defects were filled with new bone in a period of 30 days in four of five dogs.
      Histologic analysis and fluorochrome microscopy confirmed the formation of new
      cortical bone. Our results suggest that distraction osteogenesis is successful in
      previously radiated bone and that it may be a simple method of mandibular
      reconstruction following ablative head and neck surgery.

PMID- 8278473
TI  - The war against specialists.

PMID- 8278474
TI  - Cranial reshaping of rare concordant dizygotic twins with trigonocephaly.
AB  - Craniofacial surgery for craniosynostosis is now often performed, and many cases
      have been reported. Twinning among these cases is of particular interest. An
      extremely rare case of cranial reshaping of concordant dizygotic twins with
      trigonocephaly is described in this report.

PMID- 8278475
TI  - The "circummuscular" free TRAM pedicle: a trap.
AB  - A variation of the deep inferior epigastric system is presented in which the
      vessels or their dominant branches do not enter the rectus muscle at any point on
      its deep surface. Full submuscular exploration of the deep inferior epigastric
      pedicle is proposed as a necessity (prior to muscle section) if flap loss is to
      be avoided during efforts to raise free TRAM flaps with minimal muscle harvest.

PMID- 8278476
TI  - Iliohypogastric nerve entrapment following abdominoplasty.
AB  - This is a case report of iliohypogastric nerve entrapment following
      abdominoplasty with plication of the anterior rectus sheath. Persistent lower
      abdominal pain postoperatively following abdominal surgery despite a negative
      gastrointestinal and/or gynecologic workup should alert the surgeon to the
      possibility of iliohypogastric or ilioinguinal nerve entrapment. Diagnosis is
      confirmed when there are pain and sensory impairment in the distribution of the
      nerve with relief of pain following nerve block. Treatment consists of neurectomy
      with proximal resection into the retroperitoneum to avoid painful recurrent
      neuroma within the ventral abdominal wall. Prevention of injury is best
      accomplished with thorough understanding of the course of the nerve in the lower
      abdomen.

PMID- 8278477
TI  - The coronal incision revisited.
AB  - The coronal scalp incision often leaves a noticeable scar causing the hair to
      part away from it, especially when wet. Changing the straight-line to a zigzag
      incision, called the stealth incision, eliminates this obvious deformity.

PMID- 8278478
TI  - Sagittal section septoplasty: an intrinsically stabilized septoplasty.
AB  - The principles and methods of nasal septoplasty are reviewed. The design of a
      septoplasty technique based on cartilage preservation and intrinsic stabilization
      of the septum is discussed. An operative technique using sagittal incision of the
      septum to create overlapping flanges of cartilage is described. Results of
      surgical procedures by this method are reviewed, illustrative cases are
      presented, and limitations are outlined.

PMID- 8278479
TI  - Two-dimensional color Doppler imaging for precision preoperative mapping and size
      determination of TRAM flap perforators.
AB  - We have shown a new noninvasive modality for imaging periumbilical vascular
      perforators in the TRAM flap by using the two-dimensional color Doppler probe.
      This allows the precise preoperative planning of the TRAM flap to include the
      largest arterial perforators. Application of this technology may improve our
      results in TRAM flap breast reconstruction.

PMID- 8278480
TI  - J. G. Hierzel: a lip-switch flap in 1756.
AB  - After reviewing the historical aspects of the various lip-switch flaps, the
      authors draw attention to the existence of a report of a lip-switch flap
      performed in Sweden in 1756 by J.G.Hierzel.

PMID- 8278481
TI  - In situ skin grafting of free muscle flaps for the provision of intraoral lining.

PMID- 8278482
TI  - Ocular manifestations of frontonasal dysplasia.
AB  - The ophthalmologic findings associated with frontonasal dysplasia have not been
      defined previously in a large series of untreated children. We reviewed the
      ophthalmic manifestations of a series of patients with frontonasal dysplasia who
      were seen as part of their craniofacial evaluation. All had undergone a complete
      ophthalmologic examination before any manipulation of either the orbits or the
      soft tissues of the orbital contents. From 1986 to 1991, 23 patients with
      frontonasal dysplasia were seen; ophthalmologic abnormalities were found in 20
      (87 percent). Abnormalities included significant refractive errors, strabismus,
      nystagmus, and eyelid ptosis. Three patients had amblyopia, a treatable cause of
      visual loss, from strabismus or anisometropia. Ten eyes in seven patients (30
      percent) had severe structural anomalies, such as optic nerve hypoplasia, optic
      nerve colobomas, microphthalmia, cataract, corneal dermoid, or inflammatory
      retinopathy, that resulted in an acuity of 20/100 or worse. The high incidence of
      ocular abnormalities indicates that early assessment by an ophthalmologist should
      be part of the initial evaluation of patients with frontonasal dysplasia to
      detect treatable visual or ocular problems.

PMID- 8278483
TI  - Facial Impairment Scales for Clefts.
AB  - The purpose of this paper is to present the Facial Impairment Scales for Clefts.
      The Facial Impairment Scales for Clefts consist of four, 24-photograph,
      empirically derived scales of severity of cleft impairment. They were developed
      (1) to serve as research tools in single and multicenter studies of the surgical,
      psychosocial, and integrated treatment outcomes of facial clefts and (2) to
      assist in clinical assessment staging of the aesthetic severity of cleft
      impairment. Study 1 was conducted to extend the generalizability of the Facial
      Impairment Scales for Clefts to other groups of raters, including plastic
      surgeons. Reliability of scale ratings between children (n = 54) and plastic
      surgeons (n = 23) was examined. Rank orders of photographic subjects by severity
      of cleft impairment by children were highly correlated with ranks given by
      plastic surgeons. Study 2 in this series was conducted to assess if new
      photographs could be reliably fitted to scales. One-hundred and thirty-four
      medical student raters were able to scale new photographs reliably to the
      standard measures. These findings suggest that the Facial Impairment Scales for
      Clefts have sufficient reliability and validity for use in studies of severity of
      facial impairment.

PMID- 8278484
TI  - Surgical patterns of venous drainage of the free forearm flap in head and neck
      reconstruction.
AB  - A retrospective review of 40 consecutive free forearm flaps used in head and neck
      reconstruction in our Head and Neck Service identified five different patterns of
      venous drainage. In type 1, the cephalic vein and two venae comitantes join into
      a larger median cubital vein, which itself splits into two sizable branches (n =
      8, two anastomoses). In type 2, a median cubital vein drains both the cephalic
      vein and the two venae comitantes (n = 17, single anastomosis). In type 3, the
      cephalic vein and the confluence of two venae comitantes are drained separately
      (n = 7, two anastomoses). In type 4, the cephalic vein and each of two venae
      comitantes are anastomosed separately (n = 2, three separate anastomoses). In
      type 5, the cephalic vein and the larger of the two venae comitantes are drained
      separately (n = 6, two anastomoses). Understanding these possible venous drainage
      patterns substantially expedites the raising of the free forearm flap. The
      selection of patterns 1 and 2, when possible, with the large-caliber veins
      ensures the safety of the flap. Long vascular pedicles permit anastomoses to
      contralateral neck recipient vessels, obviating vein grafts, and permit safe full
      head and neck mobility.

PMID- 8278485
TI  - The nasolabial fold: an anatomic and histologic reappraisal.
AB  - The nasolabial fold was analyzed by anatomic and histologic evaluation of the
      tissue planes that create and surround the fold. A fascial-fatty layer exists in
      the superficial subdermal space extending from the upper lip across the
      nasolabial fold to the cheek mass. The SMAS is present in the upper lip as the
      superficial portion of the orbicularis oris muscle. Traction on the SMAS or
      periosteum lateral to the nasolabial fold can deepen the fold, while traction on
      the fascial-fatty layer lessens the fold. The fascial-fatty layer and skin of the
      cheek mass are suggested as the primary ptotic elements responsible for facial
      aging.

PMID- 8278486
TI  - The nasolabial fold: a photogrammetric analysis.
AB  - The nasolabial fold was analyzed by studying changes with aging in the nasolabial
      fold and adjacent soft-tissue features. Chronologic photographs were obtained
      from 19 older subjects, taken approximately every 10 years, from age 20 to their
      present age. In a separate phase of the study, facial portraits in repose and
      smiling were taken of young and old adult subjects with a mechanical frame used
      for setting an objective point of reference. Facial landmarks were identified and
      depth measurements were made in the anteroposterior direction. Relative lengths
      of selected points also were determined in the other dimensions (in the coronal
      plane) from photographs; these distances were normalized by using lower face
      length (distance from medial canthus to menton) for the vertical orientation and
      interpupillary distance to normalize horizontal dimensions. It was found that
      with aging there is anterior, lateral, and inferior displacement of the cheek
      mass with a resultant deepening of the nasolabial fold, while relationships
      between the upper lip and the fold itself remain constant. Also with age, the
      lateral commissure was found to move laterally, while the apparent angle of the
      nasolabial fold was decreased; this latter dimension was reflected by a decrease
      in the horizontal component of the fold length. These results support the theory
      that nasolabial fold deepening with age is caused by changes in the cheek mass
      and its support.

PMID- 8278487
TI  - The multiplane face lift.
AB  - The technique and experience with multiplane face lift are reviewed. The
      multiplane face lift can be thought of as a fourth-generation rhytidectomy,
      combining features of the extended SMAS and deep-plane face lifts. It is felt
      that this lift can more adequately address the problem of the nasolabial fold and
      can effect better bidirectional pull. Though difficult to quantify, it is
      expected that this lift will produce a longer-lasting result with no greater risk
      of complications than the more conventional lift. The multiplane face lift also
      can be used safely with ancillary procedures, such as blepharoplasty,
      rhinoplasty, and suction lipectomy.

PMID- 8278488
TI  - Simultaneous deep-plane face lift and trichloroacetic acid peel.
AB  - Many patients seeking facial rejuvenation require a combination of face lift and
      chemical peel to achieve optimal results. These procedures traditionally have
      been separated in time because of fear of skin slough after simultaneous peel and
      face lift. The recent evolution to deep-plane face lift and peeling agents other
      than phenol led to this reexamination of the subject. Forty-seven porcine flaps
      were treated with a variety of chemabrasion agents. As a result, 35%
      trichloroacetic acid was determined to be a safe agent for use on thick flaps.
      Thirty-five patients underwent simultaneous modified deep-plane face lift and
      immediate trichloroacetic acid peel, with 35% being the maximum strength used on
      undermined areas. This combination proved to be successful, with no complications
      related to the combination treatment.

PMID- 8278489
TI  - Recurrence of breast carcinoma following immediate reconstruction: a 13-year
      review.
AB  - To evaluate the effect of immediate reconstruction on the incidence, location,
      detection, and treatment of recurrent breast cancer, a review of 306 patients
      operated on according to a standard protocol during the 10-year period 1979
      through 1988 was performed. Reconstruction techniques included submuscular
      implants (207), tissue expanders (84), and musculocutaneous flaps (15). During a
      minimum follow-up period of 3 years with a mean of 6.4 years, 60 patients (19.6
      percent) developed recurrent disease, at a mean interval to recurrence of 31
      months. The first locations of recurrences were local (16), regional (11), and
      systemic (33). Recurrence rates by stage included stage I, 7 patients (5.2
      percent); stage II, 45 patients (32.1 percent); and stage III, 8 patients (40
      percent). It was not possible to include comparisons with internal control groups
      of patients in our institution who were not reconstructed or who had delayed
      reconstructions, thereby preventing conclusions based on such comparisons. Our
      recurrence data are similar to literature reports of recurrence rates in patients
      who were not reconstructed after mastectomy. Detection and treatment of
      recurrences were not inhibited by the reconstructions. When radiation therapy was
      used in the treatment of local recurrences, the development of symptomatic
      capsular contracture was recorded in 58 percent of the patients.

PMID- 8278490
TI  - Protein targeting to the vacuole in plant cells.

PMID- 8278491
TI  - Partial purification of the cyanide-resistant alternative oxidase of skunk
      cabbage (Symplocarpus foetidus) mitochondria.
AB  - A partial purification of the cyanide-resistant, alternative oxidase from skunk
      cabbage (Symplocarpus foetidus L.) spadix mitochondria is described. Skunk
      cabbage mitochondria were solubilized in N,N-bis-(3-D-glucon-amido
      propyl)deoxycholamide and the alternative oxidase was purified using a batch DEAE
      cellulose treatment, followed by precipitation with Extracti-Gel and
      chromatography on Sephadex G-200. Following pooling and concentrating of the most
      active fractions from the gel filtration column, a 20- to 30-fold purification of
      the alternative oxidase was obtained, with no evidence of contamination by
      cytochrome c oxidase (complex IV) or cytochrome c reductase (complex III).
      Polyacrylamide gel electrophoresis of the partially purified oxidase showed major
      polypeptides at 36 and 29 kD, both of which react with monoclonal antibodies
      raised against the Sauromatum guttatum alternative oxidase. The purified oxidase
      fraction showed no absorbance in the visible spectral region, and addition of
      sodium borohydride induced no absorbance changes in the ultraviolet region. The
      purified alternative oxidase catalyzed the four-electron reduction of oxygen to
      water in the absence of citrate, but catalyzed an apparent two-electron reduction
      of oxygen to hydrogen peroxide in the presence of 0.7 M citrate.

PMID- 8278492
TI  - Expression of Escherichia coli phosphoenolpyruvate carboxylase in a
      cyanobacterium. Functional complementation of Synechococcus PCC 7942 ppc.
AB  - The gene (ppc) coding for phosphoenolpyruvate carboxylase (PEPCase) in the
      cyanobacterium Synechococcus PCC 7942 has been inactivated via insertional
      mutagenesis while being functionally complemented by Escherichia coli ppc.
      Cyanobacterial cells functionally complemented by E. coli ppc showed decreased
      PEPCase activity in crude cell lysates and detergent-permeabilized whole cell
      assays. Decreased rates of growth, reduced levels of chlorophyll a, and decreased
      photosynthetic O2 evolution capacity per cell when compared to wild-type
      cyanobacterial cells were also observed. Phycobiliprotein levels were not
      affected. The results are discussed in terms of the impact of reduced PEPCase
      activity on cyanobacterial cell metabolism and the regulatory properties of the
      E. coli gene product.

PMID- 8278493
TI  - Insensitivity of barley endosperm ADP-glucose pyrophosphorylase to 3
      phosphoglycerate and orthophosphate regulation.
AB  - Crude extracts of starchy endosperm from barley (Hordeum vulgare cv Bomi)
      contained high pyrophosphorolytic activity (up to 0.5 mumol of glucose-1-P formed
      min-1 mg-1 of protein) of ADP-glucose pyrophosphorylase (AGP) when assayed in the
      absence of 3-phosphoglycerate (3-PGA). This high activity was observed regardless
      of whether AGP had been extracted in the presence or absence of various protease
      inhibitors or other protectants. Western blot analysis using antibodies specific
      for either the small or large subunit of the enzyme demonstrated that the large,
      60-kD subunit was prone to proteolysis in crude extracts, with a half-time of
      degradation at 4 degrees C (from 60 to 53 to 51 kD) on the order of minutes. The
      presence of high concentrations of protease inhibitors decreased, but did not
      prevent this proteolysis. The small, 51-kD subunit of barley endosperm AGP was
      relatively resistant to proteolysis, both in the presence or absence of protease
      inhibitors. For the crude, nonproteolyzed enzyme, 3-PGA acted as a weak activator
      of the ADP-glucose synthetic reaction (about 25% activation), whereas in the
      reverse reaction (pyrophosphorolysis) it served as an inhibitor rather than an
      activator. For both the synthetic and pyrophosphorolytic reactions, inorganic
      phosphate (Pi) acted as a weak competitive or mixed inhibitor of AGP. The
      relative insensitivity to 3-PGA/Pi regulation has been observed with both the
      nonproteolyzed crude enzyme and partially purified (over 60-fold) AGP, the latter
      characterized by two bands for the large subunit (molecular masses of 53 and 51
      kD) and one band for the small subunit (51 kD). Addition of 3-PGA to assays of
      the partially purified, proteolyzed enzyme had little or no effect on the Km
      values of all substrates of AGP, but it reduced the Hill coefficient for ATP
      (from 2.1 to 1.0). These findings are discussed with respect to previous reports
      on the structure and regulation of higher plant AGP.

PMID- 8278494
TI  - Identification of a basic glycoprotein induced by ethylene in primary leaves of
      azuki bean as a cationic peroxidase.
AB  - Ethylene causes the accumulation of seven different proteins (each designated
      AZxx according to its molecular mass, xx in kD) in excised primary leaves of
      azuki bean (Vigna angularis) (F. Ishige, H. Mori, K. Yamazaki, H. Imaseki [1991]
      Plant Cell Physiol 32: 681-690). A complementary DNA encoding an ethylene-induced
      basic glycoprotein, AZ42, from azuki bean was cloned and its complete nucleotide
      sequence was determined. Characterization of the cDNA was accomplished by
      monitoring expression of an immunoreactive protein in Escherichia coli that
      harbored the cDNA and by the identification of a partial amino acid sequence that
      was the same as that determined from the purified protein. An open reading frame
      (1071 base pairs) in the cDNA encoded a protein of 357 amino acids with a
      molecular mass of 39.3 kD. The amino acid sequence contained three regions that
      are highly conserved among peroxidases from eight different plants. Purified AZ42
      exhibited peroxidase activity. The basic glycoprotein induced by ethylene was
      identified as a cationic isozyme of peroxidase. The corresponding mRNA was not
      present in leaves that had not been treated with ethylene, but it appeared after
      1 h of treatment with ethylene and its level increased for the next 15 h.
      Accumulation of the mRNA was also induced after wounding or treatment with
      salicylate. The wound-induced increase in the level of the mRNA was suppressed by
      2,5-norbornadiene, but the salicylate-induced increase was not.

PMID- 8278495
TI  - Stress responses and metabolic regulation of glyceraldehyde-3-phosphate
      dehydrogenase genes in Arabidopsis.
AB  - We report here effects of three environmental conditions, heat shock, anaerobic
      treatment, and carbon source supply, on expression of nuclear genes encoding
      chloroplast (GapA and GapB) and cytosolic (GapC) glyceraldehyde-3-phosphate
      dehydrogenase from Arabidopsis thaliana. The steady-state mRNA level of the GapC
      increased when Arabidopsis plants were transferred from normal growth condition
      to heat-shock, anaerobiosis, or increased sucrose supply conditions. In contrast,
      the steady-state mRNA levels for GapA and GapB genes were unaffected or decreased
      transiently under the same treatments. To identify the cis-acting regulatory
      elements, transgenic tobacco plants containing a 820-bp GapC 5'-flanking DNA
      fragment and beta-glucuronidase (Gus) fusion were constructed. Analyses of these
      transgenic plants indicate that this 820-bp DNA fragment is sufficient to confer
      both heat-shock and anaerobic responses. These results suggest that
      transcriptional level control is involved in regulation of GapC expression under
      these stress conditions. Histochemical analysis of Gus activity indicates that
      expression of the GapC is cell-type specific and is probably linked to the
      metabolic activity of the cells.

PMID- 8278496
TI  - Light-induced biogenesis of light-harvesting complex I (LHC I) during chloroplast
      development in barley (hordeum vulgare). Studies using cDNA clones of the 21- and
      20-kilodalton LHC I apoproteins.
AB  - The light-harvesting complex (LHC) Ib pigment-proteins form the major component
      of the LHC I complex in higher plants. They comprise chlorophylls a and b,
      xanthophylls, and at least two polypeptide subunits of 21 and 20 kD in barley
      (Hordeum vulgare). We have identified two cDNA clones, LHC Ib-21 and LHC Ib-20,
      encoding the 21- and 20-kD LHC Ib apoproteins, respectively. N-terminal protein
      sequences of the purified LHC Ib polypeptides were used for the unequivocal
      correlation of these clones to their respective apoproteins. The cDNA clones
      encode two proteins that have strong sequence similarity to other LHC I and LHC
      II pigment-binding polypeptides of photosystems I and II. The 21-kD polypeptide
      contains 201 amino acid residues (22.14 kD), and the 20-kD polypeptide contains
      200 amino acid residues (22.18 kD). The biogenesis of the LHC Ib apoproteins and
      the pigmented LHC I during the light-induced development of the chloroplast was
      studied. Accumulation of the two LHC Ib mRNAs is induced by light, and their
      amount is regulated by phytochrome. LHC Ib polypeptide accumulation in the
      thylakoid membrane temporally lags behind transcript accumulation. The rates of
      accumulation of LHC Ib transcripts and of their apoproteins lag behind those of
      the major LHC II component, LHC IIb. Complete assembly of the LHC Ib pigment
      protein, as observed by low-temperature fluorescence spectroscopy, requires
      exposure of dark-grown seedlings to 72 h or more of light.

PMID- 8278497
TI  - ent-kaurene biosynthesis is enhanced by long photoperiods in the long-day plants
      Spinacia oleracea L. and Agrostemma githago L.
AB  - The effect of photoperiod on ent-kaurene biosynthesis was determined in the long
      day (LD) plants spinach (Spinacia oleracea L.) and Agrostemma githago L. Further
      metabolism of ent-kaurene was blocked by application of the growth retardant
      tetcyclacis, and ent-kaurene accumulation was measured by isotopic dilution using
      gas chromatography-selected ion monitoring (GC-SIM) (E. Grosselindemann, J.E.
      Graebe, D. Stockl, P. Hedden [1991] Plant Physiol 96: 1099-1104). In spinach, the
      rate of ent-kaurene accumulation in shoots grown under LD conditions was 3 times
      higher than in shoots grown under short-day (SD) conditions. ent-Kaurene also
      accumulated in fully expanded leaves, but at a lower rate than in shoots (15 and
      55 pmol g-1 dry weight h-1, respectively). In Agrostemma, ent-kaurene accumulated
      at a rate 2.5 times higher in plants grown under LD conditions than in those
      grown under SD conditions. In spinach, enhanced ent-kaurene accumulation was
      detectable after 1 long day, and with exposure to additional long days, the rate
      of ent-kaurene accumulation increased further. Conversely, when plants were
      exposed to LD conditions and then returned to SD conditions, the rate of ent
      kaurene accumulation decreased. Following tetcyclacis application, ent-kaurene
      accumulation was observed in all parts of spinach that were analyzed, but there
      were large quantitative differences between organs of different ages. As the
      leaves matured, ent-kaurene biosynthesis declined. Petioles accumulated more ent
      kaurene than the corresponding leaf blades. It is concluded that stimulation of
      ent-kaurene biosynthesis by LD conditions leads to a higher rate of gibberellin
      biosynthesis, which is essential for stem elongation in rosette plants.

PMID- 8278498
TI  - Expression of DcPRP1 is linked to carrot storage root formation and is induced by
      wounding and auxin treatment.
AB  - A carrot (Daucus carota, L.) genomic clone (DcPRP1) was isolated on the basis of
      its homology to previously described cDNAs encoding a wound-inducible, proline
      rich cell wall protein. DNA sequence analysis showed that DcPRP1 contains a
      single open-reading frame encoding a 235-amino acid protein that is colinear with
      that predicted from the cDNA sequence with the exception of four amino acids at
      the N terminus and a 60-nucleotide insertion present within the genomic clone.
      Genomic Southern hybridization analysis showed that the cloned sequence
      hybridized with a single restriction enzyme fragment using several restriction
      enzymes. Primer extension and northern hybridization analysis indicated that the
      expression of DcPRP1 is developmentally regulated and linked to the formation of
      storage roots, where this gene is expressed at high levels after wounding. The
      level of DcPRP1 mRNA was greatest in tissue immediately adjacent to the wound
      site. Treatment of unwounded carrot storage roots with 10 microM 2,4
      dichlorophenoxy-acetic acid, indoleacetic acid, or naphthalene-1-acetic acid also
      resulted in the accumulation of DcPRP1 transcripts to a level equal to that seen
      in wounded tissue.

PMID- 8278500
TI  - Cloning and nucleotide sequence of a tobacco chloroplast translational elongation
      factor, EF-Tu.

PMID- 8278499
TI  - Partial sequence analysis of 130 randomly selected maize cDNA clones.
AB  - As part of a project to identify novel maize (Zea mays L. cv B73) genes
      functionally, we have partially sequenced 130 randomly selected clones from a
      maize leaf cDNA library. Data base comparisons revealed seven previously
      sequenced maize cDNAs and 18 cDNAs with sequence similarity to related maize
      genes or to genes from other organisms. One hundred five cDNAs show little or no
      similarity to previously sequenced genes. Our results also establish the
      suitability of this library for large-scale sequencing in terms of its large
      insert size, proper insert orientation, and low duplication rate.

PMID- 8278501
TI  - Cloning and sequencing of a full-length cDNA clone encoding the PSI-D subunit of
      photosystem I from barley.

PMID- 8278502
TI  - Phytochrome levels in the green alga Mesotaenium caldariorum are light regulated.
AB  - Experiments undertaken in this investigation examine the influence of light on
      the levels of phytochrome in the green alga Mesotaenium caldariorum and also
      provide partial protein sequence of the algal phytochrome. Immunochemical and
      spectrophotometric measurements reveal that phytochrome levels increase nearly 4
      fold upon transfer of light-grown algal cells to total darkness during a 6- to 8
      d adaptation period. Within 24 h after return to continuous illumination, the
      level of phytochrome in dark-adapted cells has decreased to that found in light
      grown cells. Red or far-red light experiments show that both effects of light,
      phytochrome accumulation during dark adaptation and light-dependent decrease of
      phytochrome, do not depend on the form of the phytochrome photoreceptor (i.e. far
      red absorbing or red absorbing) present in the algal cell. The light-dependent
      reduction of phytochrome in dark-adapted cells is inhibited by the photosynthetic
      electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethyl urea, suggesting
      that this light effect is mediated by photosynthesis. Microsequence analyses of
      internal peptides indicate that algal phytochrome purified from dark-adapted
      cells shares the greatest sequence identity with phytochrome from the fern
      Selaginella (74%). Compared with higher plant photoreceptors, Mesotaenium
      phytochrome appears to be more closely related to phyB gene products (i.e. 62 and
      63% average sequence identity) than to phyA gene products (i.e. 50 and 53%
      average sequence identity). Because light regulation and the structure of
      Mesotaenium phytochrome do not conform with either type I (light-labile) or type
      II (light-stable) phytochromes from higher plants, these results support the
      hypothesis that the lower green plant photoreceptors represent a distinct class
      of phytochrome.

PMID- 8278503
TI  - Genetic analysis with random amplified polymorphic DNA markers.

PMID- 8278504
TI  - Nuclear targeting of the maize R protein requires two nuclear localization
      sequences.
AB  - Previous genetic and structural evidence indicates that the maize R gene encodes
      a nuclear transcriptional activating factor. In-frame carboxyl- and amino
      terminal fusions of the R gene to the reporter gene encoding beta-glucuronidase
      (GUS) were sufficient to direct GUS to the nucleus of the transiently transformed
      onion (Allium cepa) epidermal cells. Further analysis of chimeric constructs
      containing regions of the R gene fused to the GUS cDNA revealed three specific
      nuclear localization sequences (NLSs) that were capable of redirecting the GUS
      protein to the nucleus. Amino-terminal NLS-A (amino acids 100-109, GDRRAAPARP)
      contained several arginine residues; a similar localization signal is found in
      only a few viral proteins. The medial NLS-M (amino acids 419-428, MSERKRREKL) is
      a simian virus 40 large T antigen-type NLS, and the carboxyl-terminal NLS-C
      (amino acids 598-610, MISESLRKAIGKR) is a mating type alpha 2 type. NLSs M and C
      are independently sufficient to direct the GUS protein to the nucleus when it is
      fused at the amino terminus of GUS, whereas NLS-A fused to GUS partitioned
      between the nucleus and cytoplasm. Similar partitioning was observed when
      localization signals NLS-A and NLS-C were independently fused to the carboxy
      terminal portion of GUS. A sequential deletion of the localization signals
      indicated that the amino-terminal and carboxyl-terminal fusions of R and GUS were
      redirected to the nucleus only when both NLS-A and -M, or NLS-C and -M, were
      present. These results indicate that multiple localization signals are necessary
      for nuclear targeting of this protein. The conservation of the localization
      signals within the alleles of R and similar proteins from other organisms is also
      discussed.

PMID- 8278505
TI  - Characterization of a maize root proteinase.
AB  - The major proteinase in maize (Zea mays) roots behaves as a serine endopeptidase.
      A possible physiological role of this enzyme could be in the turnover of nitrate
      reductase (NR) and, as such, it could be of great importance in regulating the
      assimilation of nitrate. The objective of this research was to elucidate the
      specificity and uniqueness of maize root proteinase. When bovine serum albumin
      and an NR purified from Chlorella vulgaris were used as substrates, the maize
      root proteinase exhibited a preference for cleavages such that the amino acid on
      the amino side of the scissile bond was alanine. This information was established
      by microsequence analysis of the N termini of proteolytic fragments, and
      carboxypeptidase Y analysis of the C termini of proteolytic fragments of
      substrates hydrolyzed by the proteinase. Cleavage occurred at the sequence
      Ala/Ala-Ala-Ala-Pro-Glu in Chlorella NR, and at the sequence Ala-Asp-Glu-Ser-His
      Ala-Gln in bovine serum albumin. When bovine serum albumin was the substrate, the
      maize root proteinase yielded a peptide map that is unique relative to those
      created with the other serine endopeptidases elastase, trypsin, or chymotrypsin.
      Based on our data, the maize root proteinase appears to cleave peptide bonds at
      the carboxy side of alanine. Because of its specificity, it should have useful
      applications in protein chemistry.

PMID- 8278506
TI  - Arabidopsis chloroplasts dissimilate L-arginine and L-citrulline for use as N
      source.
AB  - When aseptically grown on defined medium with either L-arginine, L-citrulline, or
      nitrate as the sole N source, Arabidopsis plants grew and developed normally.
      Three catabolic activities, L-arginine iminohydrolase, L-ornithine
      carbamoyltransferase, and carbamate kinase, were found in stromal fractions of
      purified Arabidopsis chloroplasts. These activities dissimilate L-arginine and/or
      L-citrulline into L-ornithine, ammonium, bicarbonate, and ATP. In physiological
      tests with purified, intact Arabidopsis chloroplasts, L-[guanido-14C]arginine was
      rapidly taken up and about 10% was decomposed, releasing 14CO2. Therefore,
      chloroplasts can take up and dissimilate L-arginine. In principle, chloroplast
      arginine dissimilation allows Arabidopsis to use L-arginine and/or L-citrulline
      as general N sources for growth. However, plants rarely encounter exogenous L
      arginine and/or L-citrulline in amounts exceeding their biosynthetic needs.
      Therefore, L-arginine and L-citrulline might serve as endogenous N sources.

PMID- 8278507
TI  - Colocalization of barley lectin and sporamin in vacuoles of transgenic tobacco
      plants.
AB  - Various targeting motifs have been identified for plant proteins delivered to the
      vacuole. For barley (Hordeum vulgare) lectin, a typical Gramineae lectin and
      defense-related protein, the vacuolar information is contained in a carboxyl
      terminal propeptide. In contrast, the vacuolar targeting information of sporamin,
      a storage protein from the tuberous roots of the sweet potato (Ipomoea batatas),
      is encoded in an amino-terminal propeptide. Both proteins were expressed
      simultaneously in transgenic tobacco plants to enable analysis of their
      posttranslational processing and subcellular localization by pulse-chase labeling
      and electron-microscopic immunocytochemical methods. The pulse-chase experiments
      demonstrated that processing and delivery to the vacuole are not impaired by the
      simultaneous expression of barley lectin and sporamin. Both proteins were
      targeted quantitatively to the vacuole, indicating that the carboxyl-terminal and
      amino-terminal propeptides are equally recognized by the vacuolar protein-sorting
      machinery. Double-labeling experiments showed that barley lectin and sporamin
      accumulate in the same vacuole of transgenic tobacco (Nicotiana tabacum) leaf and
      root cells.

PMID- 8278508
TI  - Purification and sequencing of radish seed calmodulin antagonists phosphorylated
      by calcium-dependent protein kinase.
AB  - A family of radish (Raphanus sativus) calmodulin antagonists (RCAs) was purified
      from seeds by extraction, centrifugation, batch-wise elution from carboxymethyl
      cellulose, and high performance liquid chromatography (HPLC) on an SP5PW cation
      exchange column. This RCA fraction was further resolved into three calmodulin
      antagonist polypeptides (RCA1, RCA2, and RCA3) by denaturation in the presence of
      guanidinium HCl and mercaptoethanol and subsequent reverse-phase HPLC on a C8
      column eluted with an acetonitrile gradient in the presence of 0.1%
      trifluoroacetic acid. The RCA preparation, RCA1, RCA2, RCA3, and other radish
      seed proteins are phosphorylated by wheat embryo Ca(2+)-dependent protein kinase
      (CDPK). The RCA preparation contains other CDPK substrates in addition to RCA1,
      RCA2, and RCA3. The RCA preparation, RCA1, RCA2, and RCA3 inhibit chicken gizzard
      calmodulin-dependent myosin light chain kinase assayed with a myosin-light chain
      based synthetic peptide substrate (fifty percent inhibitory concentrations of
      RCA2 and RCA3 are about 7 and 2 microM, respectively). N-terminal sequencing by
      sequential Edman degradation of RCA1, RCA2, and RCA3 revealed sequences having a
      high homology with the small subunit of the storage protein napin from Brassica
      napus and with related proteins. The deduced amino acid sequences of RCA1, RCA2,
      RCA3, and RCA3' (a subform of RCA3) have agreement with average molecular masses
      from electrospray mass spectrometry of 4537, 4543, 4532, and 4560 kD,
      respectively. The only sites for serine phosphorylation are near or at the C
      termini and hence adjacent to the sites of proteolytic precursor cleavage.

PMID- 8278510
TI  - Cytosolic triosephosphate isomerase is a single gene in rice.
AB  - A cDNA clone encoding rice (Oryza sativa L.) cytosolic triosephosphate isomerase
      (TPI), an important glycolytic enzyme, was isolated and characterized. The clone
      (pRTPI-6) contains an open reading frame of 759 base pairs, encoding a
      polypeptide chain of 253 amino acid residues (M(r) 27,060). The identity of this
      clone was defined by its high homology (85% nucleotide sequence and 89% amino
      acid sequence identical match) with a maize mRNA sequence encoding the cytosolic
      TPI and with TPIs from other species. Genomic DNA blot analysis using the cDNA as
      a probe showed that the cytosolic TPI gene is present as a single copy per
      haploid rice genome, as opposed to that found in maize, in which multiple TPI
      gene copies exist. A single TPI mRNA species of about 1100 nucleotides was
      detected by gel blot hybridization analysis of RNA isolated from root, culm, and
      leaf tissues, indicating that its expression is ubiquitous. Based on sequence
      comparison and molecular analysis, we propose that the chloroplast-located TPI
      may be encoded by divergent structural nuclear genes in rice.

PMID- 8278509
TI  - Protein farnesyltransferase in plants. Molecular cloning and expression of a
      homolog of the beta subunit from the garden pea.
AB  - Protein farnesyltransferase is a heterodimeric enzyme that attaches a farnesyl
      moiety to C-terminal cysteine residues. Both the alpha and beta subunits have
      recently been cloned and sequenced from yeast and rat. Degenerate
      oligonucleotides, corresponding to conserved regions of the beta subunit, were
      used as primers for the polymerase chain reaction to amplify cDNA synthesized
      from total cellular RNA from the apical buds of pea (Pisum sativum L.) seedlings.
      The 171-bp fragment obtained encodes an open reading frame of 57 amino acids
      showing 65% identity to the rat protein farnesyltransferase beta subunit. Using
      this fragment to screen a pea cDNA library, one full-length cDNA clone,
      designated PsFTb, was obtained that contains an open reading frame encoding a
      polypeptide of 419 amino acids. The predicted amino acid sequence exhibits 48 and
      40% identity to the rat and yeast beta subunits, respectively, indicating that
      this cDNA encodes a pea homolog of the beta subunit of farnesyltransferase. Gel
      blot hybridizations show that PsFTb is likely to be encoded by a single-copy gene
      and is expressed as a transcript of approximately 1.7 kb. During photoregulated
      leaf development in continuous white light, PsFTb transcript levels within apical
      buds decline by approximately 5-fold.

PMID- 8278511
TI  - A cDNA sequence encoding 1-aminocyclopropane-1-carboxylate oxidase from pea.

PMID- 8278512
TI  - A cDNA sequence from kiwifruit homologous to 1-aminocyclopropane-1-carboxylic
      acid oxidase.

PMID- 8278513
TI  - Nucleotide sequence of a cDNA clone encoding the precursor of ribulose-1,5
      bisphosphate carboxylase small subunit from Malus.

PMID- 8278514
TI  - Cotton Lea5 and Lea14 encode atypical late embryogenesis-abundant proteins.

PMID- 8278515
TI  - Cotton (Gossypium hirsutum) MatP6 and MatP7 oleosin genes.

PMID- 8278516
TI  - Nucleotide sequence of a cDNA encoding a low molecular weight sulfur-rich protein
      in soybean seeds.

PMID- 8278517
TI  - Nucleotide sequence of the psaE gene of cyanobacterium Synechococcus sp. PCC
      6301.

PMID- 8278518
TI  - Nucleotide and deduced amino acid sequence of the 22-kilodalton cathepsin D
      inhibitor protein of potato (Solanum tuberosum L.).

PMID- 8278519
TI  - Nucleotide sequence of a cDNA clone encoding tomato (Lycopersicon esculentum)
      cysteine proteinase.

PMID- 8278520
TI  - An mRNA putatively coding for an O-methyltransferase accumulates preferentially
      in maize roots and is located predominantly in the region of the endodermis.
AB  - ZRP4, a 1.4-kb mRNA that preferentially accumulates in roots of young Zea mays L.
      plants, was identified by isolation of the corresponding cDNA clone. Genomic
      Southern analysis indicates that the zrp4 gene is represented once in the corn
      genome. The deduced ZRP4 polypeptide of 39,558 D is rich in leucine, serine, and
      alanine. Comparison of the deduced ZRP4 polypeptide sequence to polypeptide
      sequences of previously cloned plant and animal genes indicates that ZRP4 may be
      an O-methyltransferase. The ZRP4 mRNA preferentially accumulates in young roots
      and can be detected only at low levels in leaf, stem, and other shoot organs.
      ZRP4 mRNA accumulation is developmentally regulated within the root, with very
      low levels of accumulation in the meristematic region, higher levels in the
      regions of cell elongation, highest levels in the region of cell maturation, and
      low levels in the mature regions of the root. ZRP4 mRNA is predominantly located
      in the endodermis, with lower levels in the exodermis. An intriguing possibility
      is that the ZRP4 mRNA may code for an O-methyltransferase involved in suberin
      biosynthesis.

PMID- 8278521
TI  - Regulation of tobacco acetolactate synthase gene expression.
AB  - Acetolactate synthase (ALS) catalyzes the first common step in the biosynthesis
      of isoleucine, leucine, and valine. The previous cloning of two tobacco
      (Nicotiana tabacum) ALS genes (SurA and SurB) has allowed transcript accumulation
      from these genes to be monitored. mRNA blot analysis of ALS transcripts showed a
      message size of 2.2 kb. Quantitation of the levels of ALS messages in tobacco
      organs indicated that there was 3- to 4-fold variation in the levels of
      expression of the ALS genes in different organs. This variability correlated with
      the developmental stage of the samples, with the highest levels of expression
      found in developing organs. In situ hybridizations of anti-mRNA probes to plant
      sections established that ALS messages are most prevalent in metabolically active
      and dividing cells of roots, stems, and floral tissue. Using RNase protection
      assays, the transcriptional start sites of the ALS genes were determined, and the
      expression levels of the two tobacco ALS genes were then followed separately.
      Both tobacco ALS genes are expressed in a coordinated manner in all tobacco
      organs examined, with the SurB gene being consistently expressed at higher levels
      than the SurA gene.

PMID- 8278522
TI  - Expression patterns of duplicate tryptophan synthase beta genes in Arabidopsis
      thaliana.
AB  - Expression of the two Arabidopsis thaliana genes encoding tryptophan synthase
      beta (TSB1 and TSB2) was investigated by gene-specific RNA blot hybridization and
      reporter gene analysis. TSB1 mRNA abundance varies in an organ-specific manner,
      whereas TSB2 mRNA does not. Quantitative analysis of transgenic plants expressing
      TSB1 and TSB2 translational fusions to the beta-glucuronidase (GUS) gene (gusA)
      indicates that TSB1-GUS activity is 15-fold higher than TSB2-GUS. Histochemical
      analysis of these transgenic A. thaliana plants indicates that GUS expression
      occurs in a developmentally regulated manner. GUS activity driven from the TSB1
      promoter is predominantly associated with the stem, root tips, foliar
      vasculature, mesophyll cells, base of developing seed pods, and tips of anther
      filaments in plants 15 d and older. Sections through the vegetative stem reveal
      GUS staining in all cell types including the shoot apical meristem. Although TSB2
      GUS expression is consistently detected in root tips and at the base of
      developing seed pods, it is observed later in plant development than is TSB1-GUS
      expression.

PMID- 8278523
TI  - Primary structure and characterization of a cDNA clone of fructokinase from
      potato (Solanum tuberosum L. cv record).

PMID- 8278524
TI  - Starch branching enzyme II from maize endosperm.

PMID- 8278525
TI  - Chlorophyll a/b-binding protein gene expression in cotton.

PMID- 8278526
TI  - A ubiquitin carrier protein cDNA from developing alfalfa embryos.

PMID- 8278528
TI  - Starch branching enzyme cDNA from Solanum tuberosum.

PMID- 8278527
TI  - The cDNA sequence of two MADS box proteins in Petunia.

PMID- 8278529
TI  - Characterization of an aspartate transcarbamoylase cDNA from pea (Pisum sativum
      L.).

PMID- 8278530
TI  - An O-acetylserine (thiol) lyase cDNA from spinach.

PMID- 8278531
TI  - Arabidopsis thaliana cDNA encoding a novel member of the EF-hand superfamily of
      calcium-binding proteins.

PMID- 8278532
TI  - Isolation of a cDNA for proteinase inhibitor I.

PMID- 8278533
TI  - Apple ripening-related cDNA clone pAP4 confers ethylene-forming ability in
      transformed Saccharomyces cerevisiae.
AB  - The apple ripening-related cDNA insert of clone pAP4 (G.S. Ross, M.L. Knighton,
      M. Lay-Yee [1992] Plant Mol Biol 19: 231-238) has previously been shown to have
      considerable nucleic acid and predicted amino acid sequence similarity to the
      insert of a tomato ripening-related cDNA clone (pTOM13) that is known to encode
      the enzyme 1-aminocyclopropane-1-carboxylate (ACC) oxidase (A.J. Hamilton, G.W.
      Lycett, D. Grierson [1990] Nature 346: 284-287; A.J. Hamilton, M. Bouzayen, D.
      Grierson [1991] Proc Natl Acad Sci USA 88: 7434-7437). The cDNA insert from the
      clone pAP4 was fused between the galactose-inducible promoter and the terminator
      of the yeast expression vector pYES2. Transformation of Saccharomyces cerevisiae
      strain F808- with this DNA construct and incubation of the yeast in the presence
      of D[+]-galactose allowed these cells to convert ACC to ethylene. The transformed
      yeast converted 1-amino-2-ethylcyclopropane-1-carboxylate isomers to 1-butene
      with the same 1R,2S-stereoselectivity as achieved by the native ACC oxidase from
      applies. Both ascorbate and Fe2+ ions stimulated the rate of the production of
      ethylene from ACC by the transformed yeast, whereas Cu2+ and Co2+ were strongly
      inhibitory; these are features of ACC oxidase. Northern analysis of the total RNA
      from nontransformed and transformed yeast showed that the ability to convert the
      ACC to ethylene was correlated with the synthesis and accumulation of a novel 1.2
      kb mRNA that hybridized to the cDNA clone pAP4. We conclude that the cDNA
      sequence of the clone pAP4 encodes ACC oxidase.

PMID- 8278534
TI  - Purification and characterization of a glutathione S-transferase from benoxacor
      treated maize (Zea mays).
AB  - A glutathione S-transferase (GST) isozyme from maize (Zea mays Pioneer hybrid
      3906) treated with the dichloroacetamide herbicide safener benoxacor (CGA-154281)
      was purified to homogeneity and partially characterized. The enzyme, assayed with
      metolachlor as a substrate, was purified approximately 200-fold by ammonium
      sulfate precipitation, anion-exchange chromatography on Mono Q resins, and
      affinity chromatography on S-hexylglutathione agarose from total GST activity
      present in etiolated shoots. The purified protein migrated during sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (PAGE) as a single band with a
      molecular mass of 27 kD. Using nondenaturing PAGE, we determined that the native
      protein has a molecular mass of about 57 kD and that the protein exists as a
      dimer. Two-dimensional electrophoresis revealed only a single protein with an
      isoelectric point of 5.75 and molecular mass of 27 kD. These results further
      suggest that the protein exists as a homodimer of two identical 27-kD subunits.
      The enzyme was most active with substrates possessing a chloroacetamide
      structure. trans-Cinnamic acid and 1-chloro-2,4-dinitrobenzene were not effective
      substrates. Apparent Km values for the enzyme were 10.8 microM for the
      chloroacetamide metolachlor and 292 microM for glutathione. The enzyme was active
      from pH 6 to 9, with a pH optimum between 7.5 and 8. An apparently blocked amino
      terminus of the intact protein prevented direct amino acid sequencing. The enzyme
      was digested with trypsin, and the amino acid sequences of several peptide
      fragments were obtained. The sequence information for the isolated GST we have
      designated "GST IV" indicates that the enzyme is a unique maize GST but shares
      some homology with maize GSTs I and III.

PMID- 8278535
TI  - Expression of the soybean (Glycine max) glutamate 1-semialdehyde aminotransferase
      gene in symbiotic root nodules.
AB  - Extracts of soybean (Glycine max) root nodules and greening etiolated leaves
      catalyzed radiolabeled delta-aminolevulinic acid (ALA) formation from 3,4
      [3H]glutamate but not from 1-[14C]glutamate. Nevertheless, those tissue extracts
      expressed the activity of glutamate 1-semialdehyde (GSA) aminotransferase, the C5
      pathway enzyme that catalyzes ALA synthesis from GSA for tetrapyrrole formation.
      A soybean nodule cDNA clone that conferred ALA prototrophy, GSA aminotransferase
      activity, and glutamate-dependent ALA formation activity on an Escherichia coli
      GSA aminotransferase mutant was isolated. The deduced product of the nodule cDNA
      shared 79% identity with the GSA aminotransferase expressed in barley leaves,
      providing, along with the complementation data, strong evidence that the cDNA
      encodes GSA aminotransferase. GSA aminotransferase mRNA and enzyme activity were
      expressed in nodules but not in uninfected roots, indicating that the Gsa gene is
      induced in the symbiotic tissue. The Gsa gene was strongly expressed in leaves of
      etiolated plantlets independently of light treatment and, to a much lesser
      extent, in leaves of mature plants. We conclude that GSA aminotransferase, and
      possibly the C5 pathway, is expressed in a nonphotosynthetic plant organ for
      nodule heme synthesis and that Gsa is a regulated gene in soybean.

PMID- 8278536
TI  - Characteristics of an Hsp70 homolog localized in higher plant chloroplasts that
      is similar to DnaK, the Hsp70 of prokaryotes.
AB  - Members of the 70-kD heat-shock protein (Hsp70) family are important cellular
      factors that are thought to mediate protein folding and assembly. A chloroplast
      localized Hsp70 homolog (Chsp70) was recently identified based on its similarity
      to DnaK, the Hsp70 homolog of Escherichia coli (D. Amir-Shapira, T. Leustek, B.
      Dalie, H. Weissbach, N. Brot [1990] Proc Natl Acad Sci USA 87: 1749-1752). To
      learn more about the function of Chsp70, we purified the protein from Spinacia
      oleracea chloroplasts by ATP-agarose affinity chromatography. A single, 75,000-D
      protein was isolated which becomes phosphorylated on a threonine residue when
      incubated with [gamma-32P]ATP and 10 mM Ca2+, a property similar to DnaK.
      Chloroplast fractionation and immunoblot analysis showed that Chsp70 is a soluble
      stromal protein. Chsp70-specific antiserum was used to clone a partial cDNA that
      shows greater homology with Hsp70 from prokaryotes than with cytoplasmic Hsp70
      from eukaryotes. The antiserum and cDNA were used to study Chsp70 expression.
      Following heat shock of spinach seedlings at 37 degrees C, Chsp70 synthesis
      increase 12-fold, the level of Chsp70 mRNA increases 5-fold, and the level of
      Chsp70 protein increases less than 2-fold. Chsp70 is constitutively expressed in
      all spinach tissues, indicating that it is likely to be localized in all plastid
      types. The highest levels occur in seeds, leaves, florets, and seedlings grown in
      the light. Lower levels occur in roots, stems, and etiolated seedlings.

PMID- 8278537
TI  - A new cold-induced alfalfa gene is associated with enhanced hardening at subzero
      temperature.
AB  - When alfalfa (Medicago sativa L. cv Apica) plants grown at room temperature are
      transferred to 2 degrees C, the temperature at which 50% of the plants fail to
      survive (LT50) decreases from -6 to -14 degrees C during the first 2 weeks but
      then increases to -9 degrees C during the subsequent 2 weeks. However, when
      plants are kept for 2 weeks at 2 degrees C and then transferred to -2 degrees C
      for another two weeks, the LT50 declines to -16 degrees C. These changes in
      freezing tolerance are paralleled by changes in transcript levels of cas15 (cold
      acclimation-specific gene encoding a 14.5-kD protein), a cold-induced gene. Cold
      activation of cas15 occurs even when protein synthesis is inhibited by more than
      90%, suggesting that cold-initiated events up to and including the accumulation
      of cas15 transcripts depend on preexisting gene products. cas15 shows little
      homology to any known gene at the nucleotide or amino acid level. The deduced
      polypeptide (CAS15) of 14.5 kD contains four repeats of a decapeptide motif and
      possesses a bipartite sequence domain at the carboxy terminus with homology to
      the reported nuclear-targeting signal sequences. Although the relative amount of
      cas15 DNA as a fraction of the total genomic DNA is similar in cultivars with
      different degrees of freezing tolerance, its organization in the genome is
      different. The possible role of cas15 in the development of cold-induced freezing
      tolerance is discussed.

PMID- 8278538
TI  - cDNA cloning of viroid-induced tomato pathogenesis-related protein P23.
      Characterization as a vacuolar antifungal factor.
AB  - A 23-kD pathogenesis-related protein (P23) is induced in tomato (Lycopersicon
      esculentum Mill, cv Rutgers) plants when infected with citrus exocortis viroid.
      This protein is homologous to the salt-induced tomato NP24 protein (I. Rodrigo,
      P. Vera, R. Frank, V. Conejero [1991] Plant Mol Biol 16: 931-934). Further
      characterization of P23 has shown that this protein accumulates in vacuoles in
      association with dense inclusion bodies. In vitro assays indicated that the
      purified P23 protein inhibits the growth of several phytopathogenic fungi. P23
      coding cDNA clones were isolated from viroid-induced and ethylene-induced
      libraries. Southern analysis showed that at least two genes could encode P23 or
      P23-related products. The accumulation of P23 protein correlated with the
      accumulation of its mRNA. Sequence analysis revealed significant differences in
      both coding and downstream untranslated regions between the cDNA sequences
      corresponding to the viroid-induced P23 and the salt stress-induced NP24
      proteins.

PMID- 8278539
TI  - Ammonium inhibition of Arabidopsis root growth can be reversed by potassium and
      by auxin resistance mutations aux1, axr1, and axr2.
AB  - A novel effect of ammonium ions on root growth was investigated to understand how
      environmental signals affect organ development. Ammonium ions (3-12 mM) were
      found to dramatically inhibit Arabidopsis thaliana seedling root growth in the
      absence of potassium even if nitrate was present. This inhibition could be
      reversed by including in the growth medium low levels (20-100 microM) of
      potassium or alkali ions Rb+ and Cs+ but not alkali ions Na+ and Li+. The
      protective effect of low concentrations of potassium is not due to an inhibition
      of ammonium uptake. Ammonium inhibition is reversible, because root growth was
      restored in ammonium-treated seedlings if they were subsequently transferred to
      medium containing potassium. It is known that plant hormones can inhibit root
      growth. We found that mutants of Arabidopsis resistant to high levels of auxin
      and other hormones (aux1, axr1, and axr2) are also resistant to the ammonium
      inhibition and produce roots in the absence of potassium. Thus, the mechanisms
      that mediate the ammonium inhibition of root development are linked to hormone
      metabolic or signaling pathways. These findings have important implications for
      understanding how environmental signals, especially mineral nutrients, affect
      plant root development.

PMID- 8278540
TI  - Light-regulated and cell-specific expression of tomato rbcS-gusA and rice rbcS
      gusA fusion genes in transgenic rice.
AB  - A previously isolated rice (Oryza sativa) rbcS gene was further characterized.
      This analysis revealed specific sequences in the 5' regulatory region of the rice
      rbcS gene that are conserved in rbcS genes of other monocotyledonous species. In
      transgenic rice plants, we examined the expression of the beta-glucuronidase
      (gusA) reporter gene directed by the 2.8-kb promoter region of the rice rbcS
      gene. To examine differences in the regulation of monocotyledonous and
      dicotyledonous rbcS promoters, the activity of a tomato rbcS promoter was also
      investigated in transgenic rice plants. Our results indicated that both rice and
      tomato rbcS promoters confer mesophyll-specific expression of the gusA reporter
      gene in transgenic rice plants and that this expression is induced by light.
      However, the expression level of the rice rbcS-gusA gene was higher than that of
      the tomato rbcS-gusA gene, suggesting the presence of quantitative differences in
      the activity of these particular monocotyledonous and dicotyledonous rbcS
      promoters in transgenic rice. Histochemical analysis of rbcS-gusA gene expression
      showed that the observed light induction was only found in mesophyll cells.
      Furthermore, it was demonstrated that the light regulation of rice rbcS-gusA gene
      expression was primarily at the level of mRNA accumulation. We show that the rice
      rbcS gene promoter should be useful for expression of agronomically important
      genes for genetic engineering of monocotyledonous species.

PMID- 8278541
TI  - Interaction of a rhizobial DNA-binding protein with the promoter region of a
      plant leghemoglobin gene.
AB  - A nucleotide sequence was identified approximately 650 bp upstream of the
      Sesbania rostrata leghemoglobin gene Srglb3 start codon, which interacts
      specifically with a proteinaceous DNA-binding factor found in nodule extracts but
      not in extracts from leaves or roots. The binding site for this factor was
      delimited using footprinting techniques. The DNA-binding activity of this factor
      was found to be heat stable, dependent on divalent cations, and derived from the
      (infecting) Azorhizobium caulinodans bacteria or bacteroids (A. caulinodans
      bacterial binding factor 1, AcBBF1). A 9- to 10-kD protein was isolated from a
      free-living culture of A. caulinodans that co-purifies with the DNA-binding
      activity (A. caulinodans bacterial binding protein 1, AcBBP1) and interacts
      specifically with its target (S. rostrata bacterial binding site 1, SrBBS1). The
      amino acid sequence of the N-terminal 27 residues of AcBBP1 was determined and
      was found to share significant similarity (46% identity; 68% similarity) with a
      domain of the herpes simplex virus major DNA-binding protein infected cell
      protein 8 (ICP8). An insertion mutation in the SrBBS1 was found to result in a
      substantial reduction of the expression of a Srglb3-gus reporter gene fusion in
      nodules of transgenic Lotus corniculatus plants, suggesting a role for this
      element in Srglb3 promoter activity. Based on these results, we propose that (a)
      bacterial transacting factor(s) may play a role in infected cell-specific
      expression of the symbiotically induced plant lb genes.

PMID- 8278542
TI  - Isolation of a mutant Arabidopsis plant that lacks N-acetyl glucosaminyl
      transferase I and is unable to synthesize Golgi-modified complex N-linked
      glycans.
AB  - The complex asparagine-linked glycans of plant glycoproteins, characterized by
      the presence of beta 1-->2 xylose and alpha 1-->3 fucose residues, are derived
      from typical mannose9(N-acetylglucosamine)2 (Man9GlcNAc2) N-linked glycans
      through the activity of a series of glycosidases and glycosyl transferases in the
      Golgi apparatus. By screening leaf extracts with an antiserum against complex
      glycans, we isolated a mutant of Arabidopsis thaliana that is blocked in the
      conversion of high-manne to complex glycans. In callus tissues derived from the
      mutant plants, all glycans bind to concanavalin A. These glycans can be released
      by treatment with endoglycosidase H, and the majority has the same size as
      Man5GlcNAc1 glycans. In the presence of deoxymannojirimycin, an inhibitor of
      mannosidase I, the mutant cells synthesize Man9GlcNAc2 and Man8GlcNAc2 glycans,
      suggesting that the biochemical lesion in the mutant is not in the biosynthesis
      of high-mannose glycans in the endoplasmic reticulum but in their modification in
      the Golgi. Direct enzyme assays of cell extracts show that the mutant cells lack
      N-acetyl glucosaminyl transferase I, the first enzyme in the pathway of complex
      glycan biosynthesis. The mutant plants are able to complete their development
      normally under several environmental conditions, suggesting that complex glycans
      are not essential for normal developmental processes. By crossing the complex
      glycan-deficient strain of A. thaliana with a transgenic strain that expresses
      the glycoprotein phytohemagglutinin, we obtained a unique strain that synthesizes
      phytohemagglutinin with two high-mannose glycans, instead of one high-mannose and
      one complex glycan.

PMID- 8278543
TI  - Reduction of ribulose biphosphate carboxylase activase levels in tobacco
      (Nicotiana tabacum) by antisense RNA reduces ribulose biphosphate carboxylase
      carbamylation and impairs photosynthesis.
AB  - The in vivo activity of ribulose-1,5-biphosphate carboxylase/oxygenase (Rubisco)
      is modulated in response to light intensity by carbamylation of the active site
      and by the binding of sugar phosphate inhibitors such as 2'-carboxyarabinitol-1
      phosphate (CA 1P). These changes are influenced by the regulatory protein Rubisco
      activase, which facilitates the release of sugar phosphates from Rubisco's
      catalytic site. Activase levels in Nicotiana tabacum were reduced by
      transformation with an antisense gene directed against the mRNA for Rubisco
      activase. Activase-deficient plants were photosynthetically impaired, and their
      Rubisco carbamylation levels declined upon illumination. Such plants needed high
      CO2 concentrations to sustain reasonable growth rates, but the level of
      carbamylation was not increased by high CO2. The antisense plants had, on
      average, approximately twice as much Rubisco as the control plants. The maximum
      catalytic turnover rate (k cat) of Rubisco decreases in darkened tobacco leaves
      because of the binding of CA 1P. The dark-to-light increase in k cat that
      accompanies CA 1P release occurred to similar extents in antisense and control
      plants, indicating that normal levels of activase were not essential for CA 1P
      release from Rubisco in the antisense plants. However, CA 1P was released in the
      antisense plants at less than one-quarter of the rate that it was released in the
      control plants, indicating a role for activase in accelerating the release of CA
      1P.

PMID- 8278544
TI  - Amino-terminal truncations of the ribulose-bisphosphate carboxylase small subunit
      influence catalysis and subunit interactions.
AB  - The first 20 residues at the amino terminus of the small subunit of spinach
      ribulose-1,5-bisphosphate carboxylase form an irregular arm that makes extensive
      contacts with the large subunit and also with another small subunit (S. Knight,
      I. Andersson, and C.-I. Branden [1990] J Mol Biol 215: 113-160). The influence of
      these contacts on subunit binding and, indirectly, on catalysis was investigated
      by constructing truncations from the amino terminus of the small subunit of the
      highly homologous enzyme from Synechococcus PCC 6301 expressed in Escherichia
      coli. Removal of the first six residues (and thus the region of contact with a
      neighboring small subunit) affected neither the affinity with which the small
      subunits bound to the large subunits nor the catalytic properties of the
      assembled holoenzyme. Extending the truncation to include the first 12 residues
      (which encroaches into a highly conserved region that interacts with the large
      subunit) also did not weaken intersubunit binding appreciably, but it reduced the
      catalytic activity of the holoenzyme nearly 5-fold. Removal of an additional
      single residue (i.e. removal of a total of 13 residues) weakened intersubunit
      binding approximately 80-fold. Paradoxically, this partially restored catalytic
      activity to approximately 40% of that of the wild-type holoenzyme. None of these
      truncations materially affected the Km values for ribulose-1,5-bisphosphate or
      CO2. Removal of all 20 residues of the irregular arm (thereby deleting the
      conserved region of contact with large subunits) totally abolished the small
      subunit's ability to bind to large subunits to form a stable holoenzyme. However,
      this truncated small subunit was still synthesized by the E. coli cells. These
      data are interpreted in terms of the role of the amino-terminal arm of the small
      subunit in maintaining the structure of the holoenzyme.

PMID- 8278545
TI  - Molecular cloning and expression of 4-coumarate:coenzyme A ligase, an enzyme
      involved in the resistance response of soybean (Glycine max L.) against pathogen
      attack.
AB  - We have isolated three classes of cDNAs that probably encode three 4
      coumarate:coenzyme A ligase (4CL) isoenzymes in soybean (Glycine max L.). The
      deduced amino acid sequences reveal several regions of extended sequence identity
      among 4CLs of all plants analyzed to date. The sequences of two of these regions
      are consistent with a domain structure proposed for a group of enzymes catalyzing
      the ATP-dependent covalent binding of AMP to their substrates during the reaction
      sequence. By using two cDNA fragments that do not cross-hybridize under the
      conditions used, we demonstrate that 4CL in soybean is very likely encoded by a
      small gene family. Members of this family are differentially expressed in soybean
      cell cultures treated with beta-glucan elicitors of Phytophthora megasperma f.
      sp. glycinea or in soybean roots infected with either an incompatible or
      compatible race of the fungus. These results are in agreement with our previous
      observation that elicitor treatment of soybean cells caused a preferential
      enhancement in the activity level of one of the 4CL isoenzymes. In soybean, 4CL
      isoenzymes possessing different substrate affinities for substituted cinnamic
      acids, and showing differential regulation to environmental stress, may play a
      pivotal role in distributing substituted cinnamate intermediates at a branch
      point of general phenylpropanoid metabolism into subsequent specific pathways.

PMID- 8278546
TI  - Identification of a major soluble protein in mitochondria from nonphotosynthetic
      tissues as NAD-dependent formate dehydrogenase.
AB  - In many plant species, one of the most abundant soluble proteins (as judged by
      two-dimensional polyacrylamide gel electrophoresis) in mitochondria from nongreen
      tissues is a 40-kD polypeptide that is relatively scarce in mitochondria from
      photosynthetic tissues. cDNA sequences encoding this polypeptide were isolated
      from a lambda gt11 cDNA expression library from potato (Solanum tuberosum L.) by
      screening with a specific antibody raised against the 40-kD polypeptide. The cDNA
      sequence contains an open reading frame of 1137 nucleotides whose predicted amino
      acid sequence shows strong homology to an NAD-dependent formate dehydrogenase (EC
      1.2.1.2) from Pseudomonas sp. 101. Comparison of the cDNA sequence with the N
      terminal amino acid sequence of the mature 40-kD polypeptide suggests that the
      polypeptide is made as a precursor with a 23-amino acid presequence that shows
      characteristics typical of mitochondrial targeting signals. The identity of the
      polypeptide was confirmed by assaying the formate dehydrogenase activity in plant
      mitochondria from various tissues and by activity staining of mitochondrial
      proteins run on native gels combined with antibody recognition. The abundance and
      distribution of this protein suggest that higher plant mitochondria from various
      nonphotosynthetic plant tissues (tubers, storage roots, seeds, dark-grown shoots,
      cauliflower heads, and tissues grown in vitro) might contain a formate-producing
      fermentation pathway similar to those described in bacteria and algae.

PMID- 8278547
TI  - Differential induction of distinct glutathione-S-transferases of wheat by
      xenobiotics and by pathogen attack.
AB  - We have previously characterized a pathogen-induced gene from wheat (Triticum
      aestivum L.) that was named GstA1 based on sequence similarities with glutathione
      S-transferases (GSTs) of maize (R. Dudler, C. Hertig, G. Rebmann, J. Bull, F.
      Mauch [1991] Mol Plant Microbe Interact 4: 14-18). We have constructed a full
      length GstA1 cDNA by combinatorial polymerase chain reaction and demonstrate by
      functional expression of the cDNA in Escherichia coli that the GstA1-encoded
      protein has GST activity. An antiserum raised against a GstA1 fusion protein
      specifically recognized a protein with an apparent molecular mass of 29 kD on
      immunoblots of extracts from bacteria expressing the GstA1 cDNA and extracts from
      wheat inoculated with Erysiphe graminis. The GstA1-encoded protein was named
      GST29. RNA and immunoblot analysis showed that GstA1 was only weakly expressed in
      control plants and was specifically induced by pathogen attack and by the GST
      substrate glutathione, but not by various xenobiotics. In contrast, a
      structurally and antigenically unrelated GST with an apparent molecular mass of
      25 kD that was detected with an antiserum raised against GSTs of maize was
      expressed at a high basal level. This GST25 and an additional immunoreactive
      protein named GST26 were strongly induced by cadmium and by the herbicides
      atrazine, paraquat, and alachlor, but not by pathogen attack. Compared with the
      pathogen-induced GST29, GST25 and GST26 showed a high affinity toward glutathione
      agarose and were much more active toward the model substrate 1-chloro-2,4
      dinitrobenzene. Thus, wheat contains at least two distinct GST classes that are
      differentially regulated by xenobiotics and by pathogen attack and whose members
      have different enzymic properties. GST25 and GST26 appear to have a function in
      xenobiotic metabolism, whereas GST29 is speculated to fulfill a more specific
      role in defense reactions against pathogens.

PMID- 8278548
TI  - Molecular heterogeneity of photosystem I. psaD, psaE, psaF, psaH, and psaL are
      all present in isoforms in Nicotiana spp.
AB  - The protein composition of photosystem I (PSI) was examined in Nicotiana spp. by
      high-resolution polyacrylamide gel electrophoresis, N-terminal amino acid
      sequencing, and immunoblot analysis. Five PSI proteins show polymorphism in an
      amphidiploid species, Nicotiana tabacum, but not in its ancestral diploid
      species, Nicotiana sylvestris and Nicotiana tomentosiformis. These Nicotiana spp.
      appear to have at least 18 PSI proteins per genome that range in molecular mass
      from 3 to 20 kD. They include the products of nuclear genes psaD, psaE, psaF,
      psaG, psaH, psaK, and psaL, the product of chloroplast gene psaC, N-terminally
      blocked proteins of 4.5 and 3.0 kD, and an unidentified protein of 12.5 kD. The
      psaD, psaF, psaH, and psaL products have two isoforms each that are distinguished
      by different mobilities in polyacrylamide gel electrophoresis, and the psaE
      product has four isoforms. The two isoforms of the psaD product have distinct
      amino acid sequences, indicating that they are encoded by different genes within
      the genome. Four isoforms of the psaE products can be classified into two groups
      by N-terminal amino acid sequence, indicating that at least two psaE genes are
      present in the genome. To examine whether the polymorphic nature of PSI is
      peculiar to Nicotiana spp., we carried out immunoblot analysis of the psaD and
      psaE products in isogenic lines of tomato (Lycopersicon esculentum), Arabidopsis
      thaliana, red bean (Vigna angularis), and corn (Zea mays). Two
      electrophoretically distinct isoforms were found for the psaD products of tomato,
      A. thaliana, and corn, and two isoforms of psaE products were detected in tomato,
      A. thaliana, and red bean. These results suggest that the nuclear-encoded
      subunits of PSI, except for the psaG and psaK products, generally have two
      isoforms.

PMID- 8278549
TI  - Monospecific polyclonal antibodies directed against purified cinnamate 4
      hydroxylase from Helianthus tuberosus. Immunopurification, immunoquantitation,
      and interspecies cross-reactivity.
AB  - We recently reported the purification of cinnamic acid 4-hydroxylase (CA4H), a
      cytochrome P-450 catalyzing the second reaction of the general phenylpropanoid
      pathway, from Jerusalem artichoke (Helianthus tuberosus L.) (B. Gabriac, D. Werck
      Reichhart, H. Teutsch, F. Durst [1991] Arch Biochem Biophys 288: 302-309). Rabbit
      polyclonal antibodies were raised against the native and denaturated
      nitrocellulose-bound enzyme. Only the immunoglobulins G (IgGs) elicited upon
      immunization with native enzyme produced strong inhibition of catalytic activity
      and good cross-reactivity on western blots. In microsomes from H. tuberosus
      tissues induced by wounding and various chemicals, a positive correlation between
      catalytic activity and amounts of immunoreactive protein on western blots was
      observed. When coupled to cyanogen bromide-activated Sepharose, purified IgGs
      selectively retained CA4H activity from solubilized plant microsomes. Acid
      elution from the immunoaffinity matrix provided a rapid procedure for high-yield
      purification of the CA4H protein. The same IgGs immunoprecipitated a single
      protein from the in vitro translation products of mRNA isolated from wounded
      tissues. The apparent molecular weight (57,000) of this polypeptide was identical
      to that of CA4H purified from tuber microsomes. Immunochemical relatedness
      between CA4H from different plant species was demonstrated by strong inhibition
      of catalytic activity and immunopurification of several orthologous enzymes,
      using IgGs directed against CA4H from H. tuberosus. However, only limited
      interspecies cross-reactivity was observed on western blots. A careful
      immunochemical analysis indicates that CA4H immunoreactivity significantly
      differs from plant to plant. Results are discussed in terms of antibody
      specificity, enzyme glycosylation, and CA4H regulation.

PMID- 8278550
TI  - The interplay of light and the circadian clock. Independent dual regulation of
      clock-controlled gene ccg-2(eas).
AB  - Ambient light is the major agent mediating entrainment of circadian rhythms and
      is also a major factor influencing development and morphogenesis. We show that in
      Neurospora crassa the expression of clock-controlled gene 2 (ccg-2), a gene under
      the control of the circadian clock and allelic to the developmental gene easy
      wettable (eas), is regulated by light in wild-type strains. Light elicits a
      direct and important physiological effect on ccg-2(eas) expression as
      demonstrated using several mutant Neurospora strains. In white collar mutants (wc
      1 and wc-2) that are "blind" to blue light, ccg-2(eas) mRNA shows no variation
      following illumination with saturating light. By contrast, ccg-2(eas) mRNA is
      photoinduced in clock-null strains such as frequency (bd;frq). The results in the
      clock mutants show that an intact circadian oscillator is not required for light
      induction of ccg-2(eas). Thus, ccg-2(eas) is subject to a dual regulation that
      involves separable regulation by light and circadian rhythm.

PMID- 8278551
TI  - A pyruvate kinase cDNA from soybean somatic embryos.

PMID- 8278552
TI  - Sequence of a poplar bark storage protein gene.

PMID- 8278553
TI  - A cDNA clone encoding Chlamydomonas reinhardtii preferredoxin.

PMID- 8278554
TI  - Cotton cotyledon cDNA encoding a peroxidase.

PMID- 8278555
TI  - Tomato (Lycopersicon esculentum) transcript induced by water deficit and
      ripening.

PMID- 8278556
TI  - Two cDNAs for tomato heat stress transcription factors.

PMID- 8278557
TI  - Cloning of an Arabidopsis ribosomal protein S28 cDNA.

PMID- 8278558
TI  - Sequence of a Brassica campestris myrosinase gene.

PMID- 8278559
TI  - A maize cDNA encoding a type II chlorophyll a/b-binding protein of photosystem
      II.

PMID- 8278560
TI  - phyB of tobacco, a new member of the phytochrome family.

PMID- 8278561
TI  - A cDNA encoding S-adenosyl-L-methionine synthetase from poplar.

PMID- 8278562
TI  - A cDNA encoding a membrane protein from sugarcane.

PMID- 8278563
TI  - [Strangeness].

PMID- 8278564
TI  - [Through strangeness to oneself].
AB  - "Being strange" as opposed to "being oneself" is part of the thinking in all
      cultures. Belonging to a given culture is actually defined by ones identity and
      by "being oneself". Both concepts--"being oneself" or "being strange"--are
      rational and related constructs. Whatever they are confronted with, for most
      human beings it is self-evident to differentiate between subject and object,
      between "being oneself" or "being strange". This explains why thinking often
      occurs in opposites or polarities, as an either/or. All "being strange" has its
      origins in one's own self. "Being strange" becomes most obvious when persons,
      gestalt or cultures strongly deviate from one's own familiar situation. It is
      part of man's disposition to be cautious, suspicious of and at distance from
      everything considered strange and different. That explains his xenophobia
      feelings and actions. Behind this attitude we can always discover one's wish to
      preserve the familiar beliefs--combined with an uneasiness to give up one's
      thinking and behaviour that is proven and routine. It is only by reflecting on
      our own culture and our own inheritance that we have the possibility to come to
      terms with our own ethnic identity and foreign behavioral patterns. If we do not
      try to understand other cultures while keeping our own cultural identity,
      tensions and violent conflicts will inevitably result.

PMID- 8278565
TI  - [Affective ambivalence and identity conflict].

PMID- 8278566
TI  - ["When the soul is depleted, the body dies". Dying and death on the island
      Nias/Indonesia].
AB  - In our society death and dying are largely displaced from everyday experiences.
      Since old rites and traditions seem antiquated and new behavioral patterns
      haven't yet developed, interaction with dying persons is ruled by helplessness
      and speechlessness. This article describes death and dying on the islands of
      Nias/Indonesia, where a big celebration is held before someone is dying.
      Relatives keep close physical contact to the dying person. Rites and Customs
      finally help the bereaved to structure their time of mourning and to express
      their grief in a socially accepted way. Thus the adat (custom, tradition) is not
      only supporting the dying person, but also helps the survivors to cope with their
      loss.

PMID- 8278567
TI  - [Who heals the healer? Shaman practice in the Himalayas].
AB  - The question has been put before: By which means or intervention does the shaman
      or faith healer effect his healing results? A new answer is attempted in this
      article in which a concrete example is being described and analysed: What do the
      shamanic healers of the Northern Magar in NW Central Nepal do, when confronted
      with a complicated birth? As neither medication or herbal treatment, nor any
      massage or obstetric manipulation is employed (methods well applied by the local
      midwife), the healing seance of the shaman has to be classified as a
      psychological manipulation of the patient. This is based on three elements:
      ritual acts during the seance; performance of mythical chants; and the presence
      of an audience. As for the chanted myths, it may be stressed that they relate
      stories which allude to the actual situation of the patient, insofar as their
      protagonist is in a similar situation as herself--only much worse. This
      overdramatisation permits the listening patient to first identify with and then
      to dis-identify from her mythical simile and to anticipate a happier end for
      herself than that related in the myth, which is always violent and tragic. The
      mechanism of healing (in our case: a successful birth) ensues from a gradual
      process of disidentification of the patient from the mythical heroine. This
      observation may be confirmed, if one compares the Magar case with similar
      ethnographic facts from other regions, both in Nepal and elsewhere. The described
      process of healing, effected through shamanic treatment, invites to a new
      comparison between this form of practice and that of Western psychoanalysis.

PMID- 8278568
TI  - [Manifestations of somatization in Nigerian patients--diagnostic attempts and
      therapeutic approaches].
AB  - Within the last decades transcultural psychiatry has been more and more concerned
      with culture-depending illness. A tendency to somatization and symbolism proofed
      to be of importance. In this study from Nigeria specific patterns of black Africa
      are presented. Special complaints such as the followings are part of different
      psychiatric disturbances: "heat in the body and in the head; crawling, heavy and
      biting sensations". In this paper the communicative aspects of these complaints
      are emphasized. The more difficult verbal communication is, especially among
      immigrants, the more important regression to body language becomes. It is not
      rare that these symptoms are part of the defense system. The content of the
      complaints must also be understood in the context of the specific educational
      rules of Nigeria where longstanding skin contact in mothering increases the
      cathexes of the body.

PMID- 8278569
TI  - [Existential analytic psychotherapy of conversion neurosis in migrant workers].
AB  - After a brief introduction into some existential-analytic points of view of the
      body and of conversion syndrome the actual socio-cultural situation of the
      migrant workers is explained with many details. For the understanding of the
      meaning of the conversion symptoms it is necessary to search for the existential
      concept of the patient which is actually in danger. The therapeutic procedure
      following this concept is demonstrated on the base of four clinical cases.

PMID- 8278570
TI  - [Clarification by the German Psychoanalytic Society of the hate for foreigners
      and violence in Germany, delivered at the general meeting of the German
      Psychoanalytic Society 19 November 1992 in Wiesbaden].

PMID- 8278571
TI  - The bcl-2 oncogene: apoptosis and neoplasia.
AB  - Cloning of the t(14;18) translocation breakpoint resulted in the identification
      of a new putative oncogene, which mapped to 18q21, termed bcl-2. The t(14;18)
      resulted in inappropriately high levels of bcl-2 expression in follicular
      lymphoma. Prospective studies using mice transgenic for a human bcl-2
      immunoglobulin minigene, intended to recreate the molecular features of the
      t(14;18), demonstrated that bcl-2 gene deregulation was oncogenic. Interestingly,
      overexpression of bcl-2 showed no demonstrable influence on rates of cellular
      proliferation. Rather, bcl-2 was found to extend cellular viability by blocking
      apoptosis. Recent studies with other oncogenes and tumor suppressor genes, such
      as c-myc and p53, have demonstrated that the deregulation of apoptosis may be of
      general significance in the development of multiple types of cancer and appears
      to be a critical event during multistep carcinogenesis. The selective induction
      of apoptosis in tumor cell populations is now being considered in the design of
      novel therapeutic interventions.

PMID- 8278572
TI  - Modifiers of radiation-induced apoptosis.
AB  - EL4 murine lymphoma cells and F9 murine teratocarcinoma cells undergo apoptosis
      like cell death after exposure to ionizing radiation. Apoptosis differs in
      several ways from classical clonogenic cell killing by radiation. We have tested
      several modifiers and radiomimetic agents in an effort to determine if the
      mechanism of induction of apoptosis by radiation differs from the mechanism of
      classical clonogenic cell killing by radiation, and consequently that these two
      end points of radiation action might be differentially modifiable. We found that
      internucleosomal DNA fragmentation, characteristics of apoptosis, can result from
      treatment of EL4 and F9 cells with agents that have diverse modes of action: tert
      butyl hydroperoxide, diazenedicarboxylic acid bis(N,N-piperidide), and etoposide.
      Hydrogen peroxide did not induce internucleosomal DNA fragmentation at
      concentrations expected to be produced by the doses of ionizing radiation that we
      used. Radiation-induced DNA fragmentation could be inhibited by 3-aminobenzamide,
      dibutryl cyclic AMP, or 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl, although
      in this respect there appear to be marked differences between the cell lines.

PMID- 8278573
TI  - Biochemical modulation of radiation-induced apoptosis in murine lymphoma cells.
AB  - Considerable effort in our laboratory has been directed toward characterizing the
      role of apoptosis as a mode of cell death in model tumors irradiated in vivo.
      These studies have shown that apoptosis is an important response in some tumors,
      correlating with tumor growth delay and tumor cure. However, the response is
      heterogeneous among both the various tumors examined and the cells in a given
      tumor, suggesting that the propensity for cells to undergo apoptosis upon
      irradiation is regulated by unknown factors in tumors. To develop a model system
      for investigating these regulatory pathways in vitro at the molecular and
      biochemical levels, we have established cells from a tumor that displays a
      dramatic apoptotic response in vivo, the TH lymphoma, in cell culture. In this
      article, we review some of the results of our studies using this model system. To
      date, we have shown that the dose-response relationship and kinetics of the
      development of apoptosis for these cells in culture are similar to what we
      observed for the tumor response in vivo. Moreover, the roles of calcium and
      signal transduction pathways as important regulatory factors in radiation-induced
      apoptosis have been defined in this system. Ultimately such investigations may
      yield the insight necessary for designing protocols to modulate apoptosis
      biochemically in irradiated normal and tumor tissues to therapeutic advantage.

PMID- 8278574
TI  - Proton stopping powers in some low-Z elements.
AB  - For some calculations, the proton stopping power in tissue must be known
      accurately. The composition of tissue was assumed to be constituted of 11
      elements; the proton stopping powers were available for hydrogen, carbon,
      nitrogen, and oxygen. Those for the remaining 7 elements for the energy range 0.5
      to 10 MeV at intervals of 0.5 MeV are evaluated and presented in this paper.
      Corrections such as the Barkas effect correction, Bloch's correction, and shell
      correction are evaluated and used in the calculation of proton stopping powers.
      Corrections for the Bethe formula for heavy ions were suggested by Barkas et al.
      (Phys. Rev. Lett. 11, 26, 1963) when they observed that the stopping powers for
      positive ions were larger than those for the negative ions with identical
      velocities. They suggested that a charge-dependent correction term be
      incorporated in the Bethe formula. Theoretical estimates of this correction
      derived by Ashley et al. (Phys. Rev. 85, 2392-2397, 1972) were used in the
      calculation of the Barkas effect. The Barkas effect correction depends on
      projectile velocity and Z. It decreases with energy. To account for the
      discrepancy between the classical and the quantum mechanical treatment of the
      Bethe formula, Bloch (Ann. Phys. 285, Chap. 18, 1933) suggested a correction to
      the stopping-power formula; this correction is also evaluated in this paper.
      Bloch's correction also decreases with energy. The shell correction needed for
      the binding of the electrons in the target atom is also calculated using Walske's
      asymptotic formula taking into account the screening effect of the atomic
      electrons of the K and L shells of the target atom. A computer program was
      written to calculate the stopping powers of protons with all these corrections
      for seven low-Z elements which are part of the tissue composition. These values
      are compared with those of other authors, and fairly good agreement is found. The
      lack of sufficient experimental information and uncertainty in the mean
      excitation energy values and shell corrections area are some of the causes for
      the differences in the evaluation of stopping power by the different authors.

PMID- 8278575
TI  - Track studies in water vapor using a low-pressure cloud chamber. I. Macroscopic
      measurements.
AB  - Techniques have been developed to operate a low-pressure cloud chamber with pure
      water vapor. Photographs have been obtained of the tracks arising in this medium
      from the passage of ionizing radiation. The sources used were low-energy X rays,
      242Cm alpha particles, and low-energy protons. Track lengths of the electrons
      were similar to those found previously in tissue-equivalent gas. W values of 35.6
      +/- 0.4 and 32.6 +/- 0.6 eV per ion pair for carbon and aluminum X rays also
      compare closely with those in tissue-equivalent gas, but are somewhat higher than
      the predictions of Monte Carlo calculations. Differential w values were obtained:
      for alpha particles of energy 5.3 MeV the value was 33.0 +/- 3.0 eV per ion pair;
      for protons of energy 390, 230, and 85 keV the values were 30.6 +/- 1.9, 31.9 +/-
      2.0, and 33.6 +/- 3.4 eV per ion pair. The energy losses of protons in water
      vapor were measured in a second (dummy) chamber used for energy calibration.
      Results support Janni's values of stopping power for protons in the energy range
      40-480 keV.

PMID- 8278576
TI  - Track studies in water vapor using a low-pressure cloud chamber. II.
      Microdosimetric measurements.
AB  - A low-pressure cloud chamber has been adapted to operate with pure water vapor.
      Photographs were obtained of tracks arising from the passage of ionizing
      radiation. The sources used were low-energy X rays, 242Cm alpha particles, and
      low-energy protons. Distributions of lineal energy, radial distances around an
      ion track, and interdroplet distances were measured and compared with the
      predictions of Monte Carlo calculations. After allowing for diffusion and the
      limitations of the geometry of the system, the measured and calculated
      distributions were found to be in good agreement.

PMID- 8278577
TI  - Electron spin resonance studies of free radicals in gamma-irradiated golden
      hamster embryo cells: radical formation at 77 and 295 K, and radioprotective
      effects of vitamin C at 295 K.
AB  - Formation of free radicals in golden hamster embryo (GHE) cells produced by gamma
      irradiation at 77 and 295 K has been studied by electron spin resonance (ESR)
      spectroscopy. The yields of free radicals in the gamma-irradiated frozen cells at
      77 K increase linearly with increasing dose in the range from 8 Gy to 1.3 kGy,
      suggesting that the mechanism of radical formation at a dose of 8 Gy is the same
      as that at 1.3 kGy. When GHE cells are irradiated with 5 kGy gamma rays at 295 K
      and then the ESR spectrum is measured at 77 K, a part of the organic radicals
      produced can be observed clearly. The organic radicals survive in GHE cells for
      more than 24 h at room temperature. The formation of the organic radicals by
      gamma irradiation is suppressed upon the addition of vitamin C to the GHE cells.
      When an aqueous solution of albumin (0.1 kg dm-3) is gamma-irradiated with 5 kGy
      at 295 K, albumin radicals are observed by ESR. The formation of the albumin
      radicals is suppressed drastically upon the addition of vitamin C. The efficient
      radioprotection of vitamin C against radical formation has been interpreted in
      terms of the scavenging of albumin radicals by vitamin C.

PMID- 8278578
TI  - Proliferation of mouse lung epithelial cells after inhalation exposure to
      239PuO2.
AB  - The aim of this study was to investigate cell proliferation in mouse lungs up to
      12 weeks after exposure to 239PuO2. CBA mice were exposed (nose-only) to 239PuO2
      to give an initial alveolar deposit of 500 Bq. The main morphological change
      observed was hypertrophy of Type II cells. The labeling index (LI) of alveolar
      cells, which was monitored by immunocytochemical detection of DNA-incorporated 5
      bromo-2'-deoxyuridine (BrdU), increased with time after exposure and was eight
      times that of controls by the end of the study. The LI of the bronchiolar cells
      was increased markedly after exposure but declined thereafter. The cell
      proliferation patterns of the alveolar and bronchiolar cells (mainly Type II and
      Clara cells, respectively) could be related to the distribution and clearance
      patterns of the deposited particles of 239PuO2 and to the effects of alpha
      particle radiation on these cells. This study showed that significant cellular
      changes, particularly cell proliferation, occurred at early times after exposure
      of mouse lung to 239PuO2. However, the relevance of these results to the late
      carcinogenic effects of 239Pu could not be assessed because of the limited
      duration of this study.

PMID- 8278579
TI  - Morphological, biochemical, and molecular changes in endothelial cells after
      alpha-particle irradiation.
AB  - The response of cultured bovine aortic endothelial (BAE) cells after exposure to
      alpha-particle radiation from chelated 212Bi has been evaluated. The results
      suggest that even relatively high doses of alpha-particle radiation from 212Bi
      (20-72 Gy) cause only minor acute changes in the morphology of BAE cells (light
      and electron microscopy) under conditions of confluent monolayer growth.
      Significant morphological changes can be detected in cells that detach from the
      monolayer, though it is unclear whether these changes represent a genuine
      response to irradiation or reflect the causes or effects of monolayer detachment
      with the consequent loss of intercellular biochemical communication. After alpha
      particle irradiation (20-40 Gy) angiotensin-converting-enzyme activity was not
      detectable in the monolayer culture medium but was significantly decreased within
      the cell monolayer. Neutral-elution-assay data demonstrated that DNA double
      strand-break (DSB) damage occurred in these cells and that about 35% of the DSBs
      were repairable.

PMID- 8278580
TI  - Tumorigenic potential of high-Z, high-LET charged-particle radiations.
AB  - The potential for radiogenic neoplasia from charged-particle irradiation has been
      estimated using the Harderian gland of the mouse as a test system. Particles
      ranging in Z from Z = 1 (proton) to Z = 41 (niobium), in energy from 228 to 670A
      MeV, and in LET from 0.4 to 464 keV/microns were produced at the Lawrence
      Berkeley Laboratory BEVALAC. Expression of the tumorigenic potential of the
      initiated cells was enhanced by hormones from isogeneic grafts of pituitaries.
      The goal of the studies was to estimate the initial slope of the relationship
      between increased tumor prevalence at 16 months after irradiation and the dose
      received. Initial slopes were measured with good precision for 60Co gamma rays
      and the Bragg plateau beams of 228A MeV 4He ions, 600A MeV 56Fe ions, and 350A
      MeV 56Fe ions. The ratio of the initial slope for these ions to that of 60Co
      gamma rays give an estimate of the maximum RBE for radiogenic neoplasia. These
      values were 2.3 for the 4He ions, 40 for 600A MeV 56Fe, and 20 for 350A MeV 56Fe.
      In the studies reported here the prevalence of tumors as the result of pituitary
      isografts was not enhanced after irradiation with 56Fe ions. It remains to be
      seen how effective pituitary isografts are for enhancement of radiogenic
      neoplasia from other ions at different LET values. A risk analysis was undertaken
      using particle fluence rather than dose as the independent variable. This
      analysis provides a value for a "cross section" expressed in microns 2. This
      parameter expresses as the increase in proportion of mice with one or more
      Harderian gland tumors per unit increase in particle fluence. The plot of the
      cross section (risk coefficient) as a function of LET is monotonic, with no clear
      evidence of a maximum value of the risk coefficient for even the highest LET
      particle used.

PMID- 8278581
TI  - Effects of X irradiation on the function of rat salivary glands at 3 and 40 days.
AB  - The purpose of this study was to examine the effects of different doses of X
      irradiation on the major rat salivary glands. The flow rates of the salivary
      glands were measured simultaneously in both parotid and submandibular glands of
      mature male Wistar rats at 3 and 40 days after head and neck irradiation with
      single doses of 2.5, 5, 7.5, 10, or 15 Gy. The parotid and submandibular glands
      were weighed at the time of saliva collection and total body weight was obtained
      weekly. Significant reductions in parotid salivary flow at 3 days and parotid and
      submandibular flow at 40 days were found. Diminished saliva output was dose
      dependent and significantly reduced at radiation exposures of 7.5 Gy and greater.
      Submandibular function deteriorated between 3 and 40 days and the extent of
      hypofunction was comparable to the parotid gland at the latter time. Parotid and
      submandibular gland weights were reduced by irradiation in a dose-dependent
      manner at both 3 and 40 days. The effects were similar for both glands at the
      latter time. Total body weight was also reduced by the head and neck irradiation
      in a dose-dependent manner. There was significant mortality in the group
      receiving 15 Gy irradiation between 7 and 14 days after irradiation. The results
      demonstrate that parotid and submandibular glands may be affected comparably by
      equal doses of head and neck irradiation when examined at later times. In the
      period immediately after irradiation, there are significant differences in the
      responses of the major salivary glands.

PMID- 8278582
TI  - A simple method to assess in vivo repair of ultraviolet radiation-induced lesions
      of specific DNA sequences of restriction sites.
AB  - Based on the direct relationship between ultraviolet irradiation of DNA and its
      susceptibility to restriction endonucleases, we have devised a simple method to
      quantify in vivo damage and repair of selected restriction sites. The simplicity
      and power of the method were demonstrated with HindIII restriction endonuclease
      and pAc360-501-beta-gal plasmid in UV-irradiated Escherichia coli cells. The
      large number of available restriction endonucleases makes the method quite
      flexible. This method provides a simple and inexpensive means to screen mutagenic
      and antimutagenic drugs that interact with the DNA repair mechanism.

PMID- 8278583
TI  - Prophylaxis of bone marrow transplant nephropathy with captopril, an inhibitor of
      angiotensin-converting enzyme.
AB  - Chronic renal failure occurs in about 20% of long-term survivors treated with
      bone marrow transplant (BMT) regimens that include total-body irradiation (TBI);
      this syndrome is called BMT nephropathy. In a previous study in a syngeneic rat
      BMT model it was shown that captopril (an inhibitor of angiotensin-converting
      enzyme) could be used to treat experimental BMT nephropathy. Current studies were
      designed to determine whether captopril could also be used to prevent BMT
      nephropathy. Rats received 14 to 18.5 Gy TBI in six fractions over 3 days
      followed by syngeneic BMT. Seven days before TBI half the rats were started on
      captopril (500 mg/liter in the drinking water). Blood urea nitrogen, ratios of
      urine protein to creatinine, serum creatinine, and blood pressure were used to
      assess renal function. In animals receiving TBI alone, BMT nephropathy developed
      3 to 6 months after transplant. At 6 months after TBI, captopril-treated animals
      had lower systolic blood pressure and better-preserved renal function than
      animals receiving TBI alone, with dose-modifying factors of about 1.3. The
      captopril treatment had no effect on bone marrow ablation by TBI. Captopril
      appears to be safe and effective in the prophylaxis of BMT nephropathy.

PMID- 8278584
TI  - Updated analyses of combined mortality data for workers at the Hanford Site, Oak
      Ridge National Laboratory, and Rocky Flats Weapons Plant.
AB  - Updated analyses of mortality data on workers at the Hanford Site, Oak Ridge
      National Laboratory (ORNL), and Rocky Flats Weapons Plant are presented with the
      objective of providing a direct assessment of health risks resulting from
      protracted low-dose exposure to ionizing radiation. For leukemia, the combined
      excess relative risk estimate was negative (-1.0 per Sv), and confidence limits
      excluded risks that were more than slightly larger than those forming the basis
      of ICRP recommendations. For all cancer except leukemia, the excess relative risk
      estimate was 0.0 per Sv, but confidence limits indicated consistency with
      estimates several times those forming the basis of ICRP recommendations. Of 24
      cancer types tested, 12 showed positive correlations with radiation dose and 12
      showed negative correlations, as would be expected by chance fluctuation. Cancer
      of the esophagus, cancer of the larynx, and Hodgkin's disease showed
      statistically significant correlations with radiation dose (P < 0.05), but these
      correlations were interpreted as likely to have resulted from bias or chance
      fluctuation. Evidence of an increase in the excess relative risk with increasing
      age at risk was found for all cancer in both Hanford and ORNL, and both
      populations showed significant correlations of all cancer with radiation dose
      among those 75 years and older. Although this age effect may have resulted from
      bias in the data, its presence suggests that risk estimates based on nuclear
      worker data be interpreted cautiously.

PMID- 8278585
TI  - Oxygen in human tumors: correlations between methods of measurement and response
      to therapy. Summary of a workshop held November 19-20, 1992, at the National
      Cancer Institute, Bethesda, Maryland.
AB  - Knowledge about the oxygenation of human tumors and its importance in the
      response to radiotherapy is crucial to the effort to develop improved treatment
      methods for radiotherapy. The measurement of oxygenation of human tumors and
      correlations with response to radiotherapy were the subjects of a recent workshop
      sponsored by the National Cancer Institute. The following methods for measuring
      oxygen or hypoxia, or a parameter related to either, were presented:
      polarographic oxygen electrodes, the comet and alkaline elution assays for
      radiation-induced DNA damage, nitroimidazole binding assays, hemoglobin
      saturation assays, magnetic resonance spectroscopy, electron spin resonance
      spectroscopy, phosphorescence imaging, and an assay for tumor interstitial
      pressure. The electron spin resonance, alkaline elution, and phosphorescence
      imaging methods have not been used in human tumors. The comet assay,
      nitroimidazole binding assays, magnetic resonance spectroscopy, cryospectroscopy,
      and near-infrared spectroscopy have been employed in human tumors, but
      correlations to treatment response have not been made. Polarographic measurements
      have indicated that the presence of hypoxia correlates with a poor response to
      radiotherapy in cervical cancers, but additional data are needed on early-stage
      disease, and with long-term follow-up on local control and survival. If these
      confirm the correlation between hypoxia and poor response to radiotherapy,
      additional tumor sites should be studied. Future clinical trials of treatments
      that sensitize, exploit, or kill hypoxic cells should identify and include the
      individual patients with hypoxic tumors. Fundamental unanswered questions
      regarding the assessment of tumor oxygenation concern the need for invasive
      procedures, the spatial resolution needed for prediction of response to
      radiotherapy, the importance of reoxygenation, differences between tumors in
      rates and degrees of reoxygenation, whether measurements made during a course of
      therapy are of value, and correlations among methods and with other predictive
      assays such as intrinsic radiosensitivity and potential doubling time.

PMID- 8278586
TI  - In memoriam Louis H. Hempelmann (1914-1993). An appreciation.

PMID- 8278588
TI  - [Stable xenon computed tomography. Methodology and clinical application].
AB  - According to the principle of the dynamic computed tomography, stable xenon
      computed tomography allows measurement of the increase in density caused by xenon
      in the brain tissue. During a period of about 4 min a patient inhales a mixture
      of xenon (33%) and oxygen. By means of a special software, this method can be
      used to calculate flowmaps and to determine the local cerebral blood flow in a 1
      cm x 1 cm areal. Stable xenon computed tomography is used mainly for cerebral
      blood flow measurements in patients with cerebrovascular diseases and also allows
      calculation of cerebral reserve capacity following stimulation of blood flow by
      the carboanhydrase inhibitor acetazolamide (Diamox).

PMID- 8278587
TI  - [Single photon emission tomography (SPECT). Cerebral function diagnosis for the
      clinical routine. Indications and radiotracers].
AB  - Nuclear medicine techniques have been powerful tools in neurology since their
      introduction. Computed tomography, magnetic resonance imaging and newer
      techniques, i.e. MR spectroscopy and angiography, sonography, Doppler sonography
      and EEG mapping with squid elements have overtaken most earlier nuclear medicine
      techniques for neurological diagnosis. Positron emission tomography is the gold
      standard for in vivo research in neurophysiology and pathology. The introduction
      of SPECT and the development of such tracers as 99mTc-HMPAO (99mTc-d,l
      hexamethylpropylenaminoxim) and, more recently, 123I-iomazenil and 123I-IBZM
      (123I-3-iodo-6-methoxybenzamide) allowed closer examination of the perfusion of
      the brain and neuroreceptor density mapping in more than the few institutions
      that can afford PET and the production of special tracers marked with a positron
      emitting nucleus. Nuclear medicine's future will be based on neuroreceptor
      density mapping, as further tracers will become commercially available and no
      other technique can probably show such low concentrations of the receptors.
      Probably MR techniques will be used for brain's perfusion measurement in future.
      For examination of a limited cerebral region xenon-enhanced CT is an alternative
      to perfusion measurements with HMPAO, or a very interesting supplement. Of the
      old techniques in nuclear medicine, examination of the liquor dynamics is still
      feasible and well supplemented by SPECT.

PMID- 8278589
TI  - [1H magnetic resonance spectroscopy in intracranial tumors and cerebral
      ischemia].
AB  - Image-guided localized proton magnetic resonance can now increasingly be used
      with clinical 1.5T MR systems. To fuel the discussion on whether spectroscopy
      will become a routine modality or whether it will remain a research tool, we
      report on our experience with a stimulated echo sequence in 60 patients harboring
      intracranial tumors and 79 patients suffering from various forms of cerebral
      ischemia. Spectroscopy was incorporated into a routine imaging protocol, and the
      parameters of TR = 1500 ms, TE = 270 ms were kept constant over a 3-year period.
      Relative changes in the metabolite concentrations were estimated from peak height
      and area calculations compared with the spectra of 66 normal volunteers. The
      spectra of the volunteers did not show significant interindividual variations,
      and there were no changes during photic stimulation in a subgroup of 6
      volunteers. All tumor patients' spectra were significantly different from those
      of normal controls. Low grade gliomas showed decreased levels of N-acetyl
      aspartate and some had elevated levels of lactate. Oligodendrogliomas had higher
      choline levels than astrocytomas. High grade gliomas had higher levels of lactate
      and lower N-acetyl-aspartate ratios. Meningiomas were characterized by absence of
      N-acetyl-aspartate, and some metastases showed a lipid signal at 1 ppm. Spectra
      of ischemic brain tissue were also abnormal, revealing lowered N-acetyl-aspartate
      and elevated lactate. The changes paralleled the severity of ischemia and
      pronounced abnormalities were associated with an inferior outcome. Further
      technical improvements, including absolute quantification of metabolite
      concentrations and smaller sensitive volumes, will allow direct monitoring of
      treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278590
TI  - [Functional imaging of the brain. Magnetoencephalography (MEG)].
AB  - Magnetencephalography (MEG) is a new diagnostic tool for the exact localization
      of the biomagnetic sources of the electrical activity of the brain. The extremely
      weak magnetic fields are generated by the postsynaptic activity of the neurons,
      acting like current dipoles. They are measured with a SQUID (superconducting
      quantum interference device). Only the tangential components of the dipoles
      contribute to the measurable field outside the head. For MEG localization of
      sources, the brain is modelled as a sphere of homogeneous electrical
      conductivity, the center of which is fitted to MR images of the head. As a model
      of the current sources a one- or two-dipole model is used. For the analysis of
      more complex sources, however, a principle component analysis (PCA) should be
      performed before the dipole analysis, or the current-density distribution should
      be used. The effect of background activity can be eliminated by alpha wave
      filtering and the dipole-density plot (DDP), which also increases the
      signal/noise ratio. MEG seems to be useful in purely functional lesions of the
      brain. A final decision on the value of MEG for routine diagnosis is not yet
      possible, however.

PMID- 8278591
TI  - [Endovascular Doppler sonography of intracranial blood vessels. Technical
      indications and potential applications].
AB  - Intravascular Doppler ultrasonography was initially performed with specially
      designed catheters and was used primarily for cardiological purposes. The recent
      introduction of a 0.018-in. flexible, steerable guide wire with an integrated 12
      MHz piezoelectric transducer (FloWire) has made it possible to use this technique
      in neuroangiography. This system allows recording of Doppler spectra and
      determination of blood flow velocities in intracranial vessels after subselective
      introduction of a standard 3-F microcatheter. The measurement of blood flow
      velocity in an AVM feeding branch of a middle cerebral artery and the
      haemodynamic effects of the vasoconstrictive substance sumatriptan on the middle
      meningeal artery are used to illustrate potential applications of intravascular
      Doppler ultrasonography in neuroangiography.

PMID- 8278592
TI  - [Basic requirements of a radiology information system (RIS)].
AB  - One of the most important problems in medicine today is quality control and the
      achievement of a cost-benefit analysis in the areas of both treatment and
      diagnosis. With modern software techniques, complex relations between medical and
      administrative data can be shown up and analysed. Preconditions are a vocabulary
      that can be processed by computer for medical facts and decisions and a database
      system capable of collecting a large amount of heterogeneous data and costing
      everything precisely. We have developed an object description language and, on
      the basis of the relational database approach, a complex system covering most
      aspects of medical and administrative data handling in radiology. The basic
      demands and elements of modern information handling in radiology are described
      and discussed.

PMID- 8278594
TI  - [Osteolysis in the distal tibia].

PMID- 8278593
TI  - [An atypical cause of a pulmonary embolism in a benign renal tumor].
AB  - The present case report describes a 20-year-old patient with a benign renal tumor
      (angiomyolipoma of the kidney). In the course of the nephrectomy a massive
      pulmonary embolism occurred with cardiac arrest. After reanimation, pulmonary
      angiography revealed a disseminated pulmonary embolism.

PMID- 8278595
TI  - Effects of SCH 23390 and sulpiride on the behaviors evoked by amphetamine and
      apomorphine in adult cats.
AB  - 1. The aim of the present study was to analyze whether the dopaminergic D1 and D2
      receptors are involved in the production of the behaviors evoked by parenteral
      administration of amphetamine and apomorphine in adult cats. 2. Fifteen mongrel
      cats of both sexes were injected, in separate sessions, with 2.5 mg/kg of
      amphetamine and 2.0 mg/kg of apomorphine. The D1 receptor blocker, SCH 23390 was
      administered (0.3 mg/kg i.p.) and after 60 min, amphetamine and apomorphine were
      again injected on different days. The same procedure was carried on with
      sulpiride in two doses (20 and 30 mg/kg i.p.). The behaviors induced by the two
      dopaminergic drugs, before and after the receptor blocker administration were
      respectively compared. The Wilcoxon signed rank test was employed for statistical
      analysis. Three independent observers recorded the behaviors. 3. SCH 23390 and
      sulpiride produced per se hypomotility and sedation, effects that were considered
      when analysing the results. Some of the behaviors produced by amphetamine
      (pupillary dilation, head movements) were slightly modified by both receptor
      blockers. SCH 23390 only modified the licking behavior produced by apomorphine.
      In contrast, sulpiride blocked almost all the behaviors elicited by apomorphine,
      especially when the 30 mg/kg dose was administered. It is concluded that the
      behaviors produced by the 2 mg/kg dose of apomorphine are evoked by its binding
      to the post-synaptic dopaminergic D2 receptors and blocked by sulpiride.

PMID- 8278596
TI  - Effects of haloperidol and SCH 23390 on acoustic startle and prepulse inhibition
      under basal and stimulated conditions.
AB  - 1. Adult Sprague-Dawley rats underwent startle testing for assessment of baseline
      startle amplitude and prepulse inhibition (PPI) of the startle reflex. 2. Animals
      were tested after administration of either: saline, a selective D1 dopamine (DA)
      receptor antagonist, a relatively selective D2 DA antagonist, or combined low
      dose D1 and D2 antagonists. 3. Changes due to antagonists were assessed with and
      without administration of the D1/D2 agonist apomorphine. 4. Testing without
      apomorphine stimulation showed that both D1 and D2 antagonists reduce baseline
      startle and enhance PPI. Further, the two antagonists exhibited a synergistic
      interaction. 5. Testing with apomorphine showed that D1 and D2 antagonists reduce
      apomorphine-induced startle enhancement. Again, the two exhibited a synergistic
      interaction. 6. For PPI, the D2 but not D1 antagonist reduced the apomorphine
      effect. However, the D1 antagonist potentiated the effect of the D2 antagonist.

PMID- 8278597
TI  - Chronic changes in thyroid hormones do not affect brain adenosine receptors.
AB  - 1. In this study, the authors examined the effects of chronic (14 days) changes
      in thyroid function on a major neuromodulatory receptor system in the brain- the
      adenosinergic system. While previous investigators have examined the effects of
      alteration in thyroid function on adenosine receptors in peripheral tissues
      (adipocytes), this is the first study to examine such effects in brain. 2. Three
      groups of male Sprague-Dawley rats were treated for 14 days with either a) oral
      PTU (0.00625%), iodine-free diet, and i.p. saline injections, b) i.p. saline
      injections, or c) i.p. triiodothyronine (25 micrograms/100 g) injections. 3.
      These manipulations reliably resulted in the production of hypothyroidism (TSH
      30.2 +/- 8.6 ng/ml), euthyroidism (TSH 2.1 +/- 0.9), and hyperthyroidism (TSH <
      0.4). 4. Treatment had no significant effect on the Bmax or Kd of [3H]DPCPX (A1
      antagonist) binding to homogenates from cerebral cortex, cerebellum or
      hippocampus; similarly, no effect on [3H]CGS-21680 (A2-agonist) binding to
      striatal homogenates was noted. 5. Similarly, quantitative autoradiographic
      studies failed to reveal consistent regional alterations unique to either hypo-
      or hyperthyroidism. 6. Incubation of sections with GppNHp resulted in the
      expected reduction (approximately 40%) in agonist binding, but there was no
      differential effect seen for either the hypo- or hyperthyroid tissues. 7. These
      preliminary findings suggest that alterations in brain adenosine receptors or G
      protein-receptor coupling are unlikely to be requisite correlates of abnormal
      thyroid hormone levels.

PMID- 8278598
TI  - Can ECT-induced cognitive effects be altered pharmacologically?
AB  - 1. A systematic review of the literature revealed twelve clinical trials that
      evaluated nine different drugs, and used three different conceptual models to
      prevent, restore or treat ECT-induced cognitive deficits. 2. This review
      indicated inconclusive results regarding clinical utility of any of the drugs. 3.
      Major factors discussed include the complexities involved in the evaluation of
      ECT-induced cognitive deficits, and the techniques of evaluating changes in
      cognitive functions. 4. Our conclusion is that future research should emphasize
      understanding the neural mechanisms related to ECT-induced cognitive deficits. We
      suggest several areas for future exploration.

PMID- 8278599
TI  - Diagnosis and pharmacotherapy of conduct disorder.
AB  - 1. There are few double-blind, placebo-controlled studies of the drug treatment
      of conduct disorders in children and adolescents. 2. The diagnosis of conduct
      disorders involves a persistent pattern of behavior in which the basic rights of
      others and standards of society are violated. 3. There is frequent comorbidity
      associated with conduct disorders including attention-deficit hyperactivity
      disorder, oppositional defiant disorder, mood disorders and substance abuse. 4.
      Childhood Conduct disorder is associated with a significant risk for adult
      psychopathology. 5. A variety of treatment approaches may be employed to combat
      conduct disorders. 6. The use of neuroleptics, lithium carbonate, stimulants and
      other agents is reviewed.

PMID- 8278600
TI  - Dopaminergic regulation of glutamic acid decarboxylase mRNA expression and GABA
      release in the striatum: a review.
AB  - 1. The majority of neurons in the striatum (caudate-putamen, dorsal striatum;
      nucleus accumbens, ventral striatum) and in striatal projection regions (the
      pallidum, the entopeduncular nucleus and substantia nigra reticulata) use gamma
      aminobutyric acid (GABA) as transmitter and express glutamic acid decarboxylase
      (GAD; rate limiting enzyme) in the synthesis of GABA. GABA is the major
      inhibitory transmitter in the mammalian brain. 2. GAD in brain is present as two
      isoenzymes, GAD65 and GAD67. GAD65 is largely present as an inactive apoenzyme,
      which can be induced by nerve activity, while most GAD67 is present as a
      pyridoxal phosphate-bound permanently active holoenzyme. Thus GAD65 and GAD67
      seem to provide a dual system for the control of neuronal GABA synthesis. 3. GAD
      mRNA expression can be visualised and quantified using in situ hybridisation, and
      GABA release can be quantified using in vivo microdialysis. 4. Different
      populations of GABA neurons can be distinguished in both dorsal and ventral
      striatum as well as in other parts of the basal ganglia. 5. Inhibition of
      dopaminergic transmission in the striatum by lesion of dopamine neurons or by
      neuroleptic treatment is followed by an increased release of GABA and increased
      expression of GAD67 mRNA in a subpopulation of striatal medium-sized neurons
      which project to the globus pallidus, and increased striatal GAD enzyme activity.
      6. Increased dopaminergic transmission by repeated but not single doses of
      amphetamine is followed by decreased striatal GABA release and decreased GAD67
      mRNA expression in a subpopulation of medium-sized neurons in the striatum. 7.
      Two populations of medium-sized GABA neurons in the striatum seem to be under
      tonic dopaminergic influence. The majority of these GABA neurons are under
      inhibitory influence, whereas a small number seem to be stimulated by dopamine.
      8. Specific changes in activity in subpopulations of striatal GABA neurons
      probably mediate the dopamine-dependent hypokinetic syndrome seen in Parkinson's
      disease and following neuroleptic treatment.

PMID- 8278601
TI  - Structure-function relationship studies in human cholinesterases reveal genomic
      origins for individual variations in cholinergic drug responses.
AB  - 1. Due to their involvement in the termination of neurotransmission at
      cholinergic synapses and neuromuscular junctions, cholinesterases are the target
      proteins for numerous drugs of neuro-psychopharmacology importance. 2. In order
      to perform structure-function relationship studies on human cholinesterases with
      respect to such drugs, a set of expression vectors was engineered, all of which
      include cloned cDNA inserts encoding various forms of human acetyl- and
      butyrylcholinesterase. These vectors were designed to be transcribed in vitro
      into their corresponding mRNA products which, when microinjected into Xenopus
      oocytes, are efficiently translated to yield their catalytically active enzymes,
      each with its distinct substrate specificity and sensitivity to selective
      inhibitors. 3. A fully automated microtiter plate assay for evaluating the
      inhibition of said enzymes by tested cholinergic drugs and/or poisons has been
      developed, in conjunction with computerized data analysis, which offers
      prediction of such inhibition data on the authentic human enzymes and their
      natural or mutagenized variants. 4. Thus, it was found that asp70-->gly
      substitution renders butyrylcholinesterase succinylcholine insensitive and
      resistant to oxime reactivation while ser 425-->Pro with gly70 gives rise to the
      "atypical" butyrylcholinesterase phenotype, abolishing dibucaine binding. 5.
      Furthermore, differences in cholinesterase affinities to physostigmine,
      ecothiophate and bambuterol were shown in these natural variants. 6. Definition
      of key residues important for drug interactions may initiate rational design of
      more specific cholinesterase inhibitors, with fewer side effects. This, in turn,
      offers therapeutic potential in the treatment of clinical syndromes such as
      Alzheimer's and Parkinson's disease, glaucoma and myasthenia gravis.

PMID- 8278602
TI  - Emotional and psychopathological disturbances in HIV-infection.
AB  - 1. The evaluation of emotional disturbances, depression and anxiety in 25 HIV
      Positive paired with 25 HIV-Negative male homosexuals and a control group of 15
      HIV-Negative male heterosexual have shown the presence of emotional perturbations
      and especially of an emotional blunting, in absence of depressive or anxious
      episode in HIV-Positive subjects. 2. Emotional perturbations were the lowest in
      the HIV-Negative heterosexual group. 3. These results raise the question of the
      emotional deficit as an adaptative process or as the direct action of the virus.
      4. Its relationship with the other emotional perturbations and their impact on
      the evolution of the disease are discussed.

PMID- 8278603
TI  - Neuropsychological deficit and aggressive behavior: a prospective study.
AB  - 1. Failures in higher cortical executive functions and dyscontrol of aggressive
      impulses were hypothesized to co-occur in aggressive men. 2. The performance of a
      sample of violent forensic patients on selected neuropsychological measures
      (Judgment of Line Orientation, Stroop Color Word Test, Emotion Perception Test,
      Test Of Nonverbal Intelligence, Wisconsin Card Sorting Test, and Symbol Digit
      Modalities Test) were used to predict their overt aggressive behavior during a
      one-year period using the Overt Aggression Scale. 3. Whole-set correlation
      analyses revealed that scores on the Judgment of Line Orientation, Stroop Color
      Word Test, and Emotion Perception Test accounted for 57% of the variance of
      aggression scores. 4. Frequency of aggression, but not severity of aggression,
      can be predicted using these three scores.

PMID- 8278604
TI  - Serine and glycine metabolism in schizophrenic patients.
AB  - 1. The brain glycine is almost exclusively derived from serine via serine
      hydroxymethyltransferase. 17 males schizophrenic inpatients and 10 males healthy
      volunteers were submitted to the serine tolerance test. 2. Plasma serine and
      glycine concentration were evaluated before and after 1, 2, 3, 4 hours of an oral
      load with L-serine to test the interconversion between the two amino acids. 3.
      The authors did not find any significant difference between schizophrenic
      patients and control group and concluded that the enzyme serine
      hydroxymethyltransferase is not deficient in the conversion of serine to glycine
      in schizophrenic patients as suggested by other authors.

PMID- 8278605
TI  - Benzodiazepine effects on flicker sensitivity: role of stimulus frequency and
      size.
AB  - 1. Benzodiazepines (BZDs) impair sensitivity to temporally modulated visual
      stimuli (flicker). Critical flicker-fusion frequency (CFF) is commonly used as a
      measure of this effect, but it only measures sensitivity to a narrow range of
      frequencies, usually above 25 Hz. Are other frequencies more sensitive to the
      effects of BZDs? 2. Flicker sensitivity at 1, 2, 4, 8, 16, and 32 Hz was measured
      for 1 degrees and 5 degrees stimuli before and 50 to 100 minutes after triazolam
      (0.25 mg), lorazepam (1.0 mg) and placebo. Drug effects on CFF were also
      measured. 3. Both BZDs significantly impaired overall flicker sensitivity.
      Triazolam produced 50% more impairment than lorazepam. CFF was significantly
      impaired by triazolam. BZD effects did not vary with stimulus size. 4.
      Significantly greater BZD-induced impairment of flicker sensitivity occurred at
      16 Hz than at 1, 2, 4, or 32 Hz. 5. The magnitude of BZD effects on flicker
      sensitivity vary with the temporal frequency of the stimulus. BZD effects are
      greatest for 8-16 Hz stimuli.

PMID- 8278606
TI  - Neutrophil and monocyte phagocytosis in depressed patients.
AB  - 1. Monocyte and neutrophil phagocytosis was investigated in a group of depressed
      patients during the active phase of their illness and following recovery. The
      results were compared with those obtained from a group of schizophrenia and manic
      patients and with age and sex matched controls. Neutrophil phagocytosis was
      reduced in all three patient groups during the active phase of the illness but
      returned to control values on recovery. Monocyte phagocytosis was however
      increased but while it returned to control values following recovery of the
      depressed patients, it remained raised in the manic and schizophrenic patients.
      2. T-cell replication in response to a mitogen challenge was also investigated in
      the depressed patients. This was found to be significantly reduced in the
      depressed patients during the active phase of the illness and remained reduced
      following their recovery. 3. The results suggest that the changes in phagocytosis
      and T-cell replication are state and trait markers respectively of depression. 4.
      A differential white blood cell count revealed that the neutrophil number was
      increased and the monocytes decreased, in the depressed patients during the
      active phase of the illness, but returned to normal values on recovery. 5. The
      factor(s) responsible for the changes in these various aspects of the immune
      function is unknown. However, evidence is presented that the changes are not due
      to hypercortisolaemia or to the direct effects of the psychotropic medication on
      phagocytosis or T-cell replication.

PMID- 8278607
TI  - Electroconvulsive shock (ECS) does not facilitate the development of kindling.
AB  - 1. For many years it has been discussed whether repeated electroconvulsive shock
      (ECS) may induce a lasting epileptogenic effect on the brain (i.e. a kindling
      effect). In the present study the authors investigated whether weekly ECS do
      exert such an effect. 2. Bipolar electrodes were implanted in amygdala of 32
      rats. Following a two to three week recovery period the rats were randomly
      allocated to two groups. One group received 12 weekly ECS, the other 12 weekly
      sham-ECS. 3. Three months after the last ECS/sham-ECS, kindling was initiated.
      Daily stimulation, eliciting an EEG-afterdischarge was given to all the rats. The
      animals received a total of 15 stimulations. 4. ECS-pretreated animals did not
      kindle faster than the sham-group. The two groups reached stage 4 (clonic
      rearing) after 5.8 (ECS-group) and 5.7 (sham-group) stimulations, respectively.
      5. The authors did not find a facilitated development of kindling following ECS,
      instead they observed a slight, yet statistically significant inhibition of the
      development of the maximally generalized kindling-seizure--the stage 5 seizure-
      in the ECS-group. 6. IN CONCLUSION: The present study did not show a kindling
      effect of weekly ECS suggesting that kindling requires more than repeated
      elicitation of after-discharge.

PMID- 8278608
TI  - Altered brain and pituitary androgen metabolism by prenatal, perinatal or pre-
      and postnatal finasteride, flutamide or dihydrotestosterone treatment in juvenile
      male rats.
AB  - 1. The authors investigated the administration of finasteride, a 5 alpha
      reductase inhibitor; flutamide, an androgen receptor blocker and; exogenous
      dihydrotestosterone (DHT) during intervals covering different portions of the
      "critical period" of neural development (i.e. prenatal, perinatal or pre- and
      postnatal development) to determine the long-term effects of these agents on
      altering androgen metabolism in hypothalamic and pituitary tissue of juvenile (30
      day-old) male rats. 2. The efficacy of the treatments and hypothalamic-pituitary
      axis function was monitored by measuring luteinizing hormone levels by
      radioimmunoassay. 5 alpha-Reductase and aromatase activity was determined in
      hypothalamic and pituitary tissue. 3. Significant alterations in pituitary 5
      alpha-reductase activity was detected in DHT-treated animals, whereas,
      hypothalamic 5 alpha-reductase activity was significantly decreased by
      finasteride treatment and significantly increased by DHT treatment. Hypothalamic
      aromatase activity was significantly decreased in flutamide-treated animals. 4.
      These results suggest that: a) prenatal exposure to exogenous DHT stimulates
      hypothalamic (but inhibits pituitary) 5 alpha-reductase activity long-term and b)
      basal 5 alpha-reductase activity levels can be inhibited by finasteride treatment
      in hypothalamic but not in pituitary tissue, suggesting that a different
      regulatory mechanism exists for 5 alpha-reductase in hypothalamic versus
      pituitary tissue.

PMID- 8278610
TI  - [Genetic control of left-right asymmetry generation].

PMID- 8278609
TI  - [Non-universal genetic codes and their evolutionary processes].

PMID- 8278611
TI  - [Functional characterization of photosynthetic genes by chloroplast
      transformation].

PMID- 8278612
TI  - [Accurate detection of heterozygous carriers of a deletion or a duplication by
      combined PCR and HPLC].

PMID- 8278613
TI  - [Allergy-like symptom caused by mite-protease].

PMID- 8278614
TI  - [Centromere function and cell cycle].

PMID- 8278615
TI  - [Molecular mechanism of spindle formation].

PMID- 8278616
TI  - The correlation between 13-hydroxyoctadecadienoate dehydrogenase (13-HODE
      dehydrogenase) and intestinal cell differentiation.
AB  - The enzyme 13-hydroxyoctadecadienoate dehydrogenase (13-HODE dehydrogenase)
      catalyzes the NAD(+)-dependent oxidation of 13-hydroxyoctadecadienoic acid to 13
      oxooctadecadienoic acid. In that the oxygenation of linoleic acid is increasingly
      being shown to be involved in the regulation of cellular function, this enzyme is
      poised to play a key role in the expression of the biological activity of these
      compounds. We have measured the activity of 13-HODE dehydrogenase in rat
      intestinal cells at various stages of differentiation. The specific activity of
      13-HODE dehydrogenase shows a strong positive correlation with the degree of
      differentiation of intestinal mucosal cells from both the small and large
      intestines. In the small intestine the gradient of activity parallels that of
      alkaline phosphatase, while in the colon the incorporation of 3H-deoxythymidine
      and 13-HODE dehydrogenase are inversely related. Since the expression of 13-HODE
      dehydrogenase is most likely not associated with the nutritive function of the
      intestinal tract, these data raise the possibility the enzyme plays a role in the
      process of cellular differentiation.

PMID- 8278617
TI  - Increased susceptibility to injury and normal reactivity to prostaglandin
      protection of mucous cells isolated from gastric mucosa of portal hypertensive
      rats.
AB  - We examined the susceptibility of mucous cells isolated from gastric mucosa of
      portal hypertensive rats to ethanol injury. In addition, we assessed their
      response to protective action of prostaglandin against ethanol injury in vitro.
      Ethanol significantly decreased cell viability in calcium-containing medium. The
      injury of mucous cells isolated from portal hypertensive rats was more extensive
      than those isolated from sham-operated rats. Ethanol-induced cell injury was
      reduced similarly in both groups by pretreatment with 16,16-dimethyl
      prostaglandin E2. These results suggest that mucous cells isolated from portal
      hypertensive gastric mucosa are more susceptible to ethanol injury and this
      susceptibility is dependent on extracellular calcium. The cells from portal
      hypertensive gastric mucosa retain, however, sensitivity to protective action of
      16,16-dimethyl prostaglandin E2.

PMID- 8278618
TI  - Phospholipase A2 activity in endometrium from early pregnant and non-pregnant
      ewes.
AB  - In the ewe, synthesis of the luteolytic factor, prostaglandin F2 alpha, increases
      from day 13 to the end of the estrous cycle. Availability of free arachidonic
      acid is usually the rate-limiting step in prostaglandin biosynthesis.
      Phospholipase A2 (PLA2) may be the key enzyme for the hydrolysis of arachidonic
      acid from membrane-bound phospholipids. To investigate uterine PLA2 activity
      during the estrous cycle and early pregnancy, we monitored the release of
      [14C]oleic acid from the substrate 1-palmitoyl-2-[14C]oleoyl-phosphorylcholine by
      homogenates and cytosolic fractions of endometrium from ewes on days 12, 14 and
      16 of the estrous cycle or pregnancy. We observed that PLA2 activity dropped by
      58% (p < 0.02) in day-16 pregnant endometrium compared to day-16 non-pregnant
      endometrium. We then investigated whether the reduced PLA2 activity was due to
      induction of a specific inhibitor. The PLA2-inhibitor activity was determined by
      monitoring the inhibition of release of [14C]oleic acid from the radioactive
      substrate by porcine pancreatic PLA2. Inhibition by endometrial homogenates of
      pregnant animals of the control enzyme activity was 27% and only 14% by cyclic
      ones. Inhibition was dose-dependent and was as high as 53% (p < 0.01) with 1 mg
      protein from pregnant endometrial homogenates. Endometrial PLA2 behaved as a
      Michaelian enzyme in the endometrium of day-16 cyclic ewes (Km = 79.4 mumol/l).
      Furthermore, the inhibitory activity from pregnant endometrium had
      characteristics of competitive inhibition. Our results suggest that inhibition of
      endometrial PLA2 activity could occur in early pregnant ewes.

PMID- 8278619
TI  - Glucose, glycogen and triglyceride metabolism, as well as prostaglandin
      production in uterine strips and in embryos from diabetic pregnant rats.
      Influences of the presence of substrate in the incubation medium.
AB  - "In vitro" isometric developed tension (IDT) and frequency of contractions (FC),
      glucose (Glu), glycogen (GLY) and triglyceride (TG) metabolism, as well as
      prostaglandin PGE2 and PGE1 production, were studied in uterine strips and in
      embryos isolated from controls and diabetic rats at day 10 of pregnancy. The IDT
      and the FC, at 0 time or after a 60 min incubation, were not different in
      controls and in preparations from diabetic animals when the uterine strips were
      incubated in glucose or in glucose-free medium (p > 0.05). The production of
      14CO2 and 14C-lactate from 14C-glucose were lower in the diabetic group than in
      controls (p < or = 0.05). Indomethacin (10(-6) M), an inhibitor of prostaglandin
      synthesis, failed to modify these results. Labelled Glu metabolism by isolated
      embryos was similar (p > 0.05) in controls and in embryos obtained from diabetic
      mothers. On the other hand, the initial TG and GLY levels were higher (p < or =
      0.05) in diabetic uterine tissues than in controls. However, the values of TG and
      GLY in embryos obtained from both experimental groups were similar (p > 0.05). TG
      levels in uterine strips suspended in Glu or in Glu-free medium did not differ (p
      > 0.05) at 0 time (postisolation) and at 60 min, either in controls or in
      diabetic rats. However, Gly levels in uterine strips from diabetic animals,
      decreased significantly at 60 min in tissues incubated in Glu or in Glu-free
      medium (p < or = 0.05). In controls, uterine Gly content decreased (p < or =
      0.05) only at 60 min time when the strips were incubated in Glu-free medium.
      Finally, uterine tissue from controls as well as from diabetic pregnant rats
      release more PGE2 than PGE1 into the incubation medium (p < or = 0.001).
      Nevertheless, secretion of PGE2 and PGE1 was similar in both experimental groups
      and was not modified by the presence or absence of glucose. In summary, we found
      differences in uterine metabolism of glucose, glycogen and triglycerides in
      controls and in diabetic rats, but metabolic differences have not been detected
      between embryos obtained from controls and from diabetic mothers.

PMID- 8278620
TI  - Localization of stress protein-70 in ovine corpora lutea during prostaglandin
      induced luteolysis.
AB  - Accumulation of heat shock (stress) protein-70 (HSP-70) was assessed in corpora
      lutea of sheep obtained after in vivo administration of a luteolytic dose of
      prostaglandin (PG) F2 alpha. A quantitative immunofluorescence technique was used
      to localize inducible HSP-70 production to specific cell-types. The number and
      intensity of immunostained large luteal cells increased within 2 h of injection
      of PGF2 alpha. A drop in luteal progesterone concentrations (functional
      regression) was not manifested until 4 h post-treatment. A dramatic increase in
      intensely-stained mononuclear leukocytes was observed in luteal tissues at 16 h,
      when glandular weights had begun to diminish (structural regression). Stress
      proteins could mediate intracellular protein processing and cell-surface
      autoimmune mechanisms underlying luteal regression.

PMID- 8278621
TI  - Lipo-PGE1, a new lipid-encapsulated preparation of prostaglandin E1: placebo-and
      prostaglandin E1-controlled multicenter trials in patients with diabetic
      neuropathy and leg ulcers.
AB  - Several clinical trials have shown that prostaglandin E1 (PGE1) is effective in
      treating peripheral occlusive vascular disease, but not definitely for diabetic
      neuropathy. We developed a new preparation of PGE1 incorporated in lipid
      microspheres (lipo-PGE1) that was designed to accumulate at vascular lesions. The
      effect of lipo-PGE1 (10 micrograms/day) was compared with placebo and the normal
      dose of a free PGE1 preparation (PGE1-CD, 40 micrograms/day) in two studies
      (double-blind and well-controlled) which enrolled 364 diabetic patients with
      neuropathy and/or leg ulcers. The drugs were given intravenously (bolus or drip
      infusion) for 4 weeks. Clinical improvement was noted in 61.6% of the lipo-PGE1
      group and 30.0% of the placebo group in Trial 1 (p < 0.01), while the figures
      were 58.3% in the lipo-PGE1 group and 37.1% in the PGE1-CD group in Trial 2 (p <
      0.01). Leg ulcers became smaller in the lipo-PGE1 groups in both trials (p <
      0.01). In Trial 2, motor conduction velocity improved in the lipo-PGE1 group (p =
      0.016). Side effects occurred in few patients receiving lipo-PGE1 or placebo, but
      more patients developed local side effects in the PGE1-CD group (p < 0.01). Thus,
      bolus intravenous injection of lipo-PGE1 improved diabetic neuropathy and leg
      ulcers with minimal side effects.

PMID- 8278622
TI  - Participation of endogenous neuropeptide Y in the suppression of baroreceptor
      reflex response by locus coeruleus in the rat.
AB  - We evaluated the potential participation of endogenous brain neuropeptide Y (NPY)
      in the suppression of baroreceptor reflex (BRR) response by locus coeruleus (LC),
      using adult male Sprague-Dawley rats anesthetized with pentobarbital sodium (40
      mg/kg, i.p.). Bilateral microinjection of an antiserum against NPY (1:20, 20 nl)
      into the caudal one-third level of the nucleus tractus solitarii (NTS), the
      terminal site for baroreceptor afferent fibers, significantly reversed the
      suppressive effect of electrical or chemical activation of the LC on the BRR
      response. Treatments with NPY (4.65 pmol, 20 nl), normal rabbit serum, aCSF and
      heat-inactivated NPY or NPY antiserum, on the other hand, were ineffective. The
      LC-promoted inhibition of the BRR response was also attenuated by the alpha 1
      adrenoceptor antagonist prazosin (50 pmol, 20 nl), either microinjected alone or
      in combination with NPY antiserum into the bilateral NTS. Mathematical treatment
      of our data revealed that the depressive effect on the BRR response of NPY or NE
      released at the NTS following LC activation manifested different time-course and
      magnitude. The one by endogenous NPY maximized at 40 min and amounted to no more
      than 20% of, whereas that by NE peaked at 10 min and contributed no less than 30%
      to, the suppression. These results suggest that both endogenous NPY and NE may
      participate in the suppression of BRR response by the LC at the NTS.

PMID- 8278623
TI  - Vasoactive intestinal peptide and helodermin inhibit phospholipase A2 activity in
      vitro.
AB  - We recently reported that the widely distributed neuropeptide vasoactive
      intestinal peptide (VIP) reduces inflammatory lung injury due to a variety of
      agents and inhibits the associated generation of cyclo-oxygenase and lipoxygenase
      products. We therefore investigated whether VIP may inhibit phospholipase A2
      activity, thus reducing the release of arachidonic acid, the common precursor of
      all eicosanoids. VIP dose-dependently inhibited PLA2 of porcine pancreas and of
      Naja naja venom, as assessed by the release of free [3H]oleic acid from labeled
      Escherichia coli phospholipids. The potency of VIP was similar to that of
      mepacrine, with 50% inhibition at 400-500 microM. The closely related peptide
      helodermin produced 50% inhibition at 200 microM, but secretin and peptide
      histidine isoleucineamide produced little or no inhibition. The results suggest
      that VIP and helodermin selectively inhibit PLA2 in vitro. If this activity is
      exerted in vivo, it may contribute to the anti-inflammatory activity of these two
      peptides.

PMID- 8278624
TI  - Neural regulation of peptide YY secretion.
AB  - The purpose of these experiments was to investigate the neural control of peptide
      YY (PYY) secretion. The effects of various pharmacological manipulations and
      vagotomy on peptide YY (PYY) secretion was examined in dogs. Atropine,
      hexamethonium and atropine plus hexamethonium treatment blocked food-induced
      release of PYY significantly. Integrated release of PYY in response to food alone
      and in combination with atropine, hexamethonium and atropine plus hexamethonium
      were 8.8 +/- 2.2, -1.1 +/- 2.3, -2.7 +/- 2.2 and -3.2 +/- 3.1 (ng (0-150)
      min/ml), respectively. beta-Adrenergic blockade with propranolol or depletion of
      nerve terminal stores of catecholamines with reserpine did not affect food
      stimulated release of PYY. Truncal vagotomy resulted in significant elevations of
      basal and food-induced release of PYY. IV administration of bethanechol, a
      cholinergic agonist, and electrical stimulation of the vagus nerve resulted in
      release of PYY. Together, these data suggest that food-stimulated PYY secretion
      is dependent on ganglionic transmission and an atropine-blockable postganglionic
      parasympathetic pathway; and that PYY release is inhibited tonically, probably
      through a vagal cholinergic mechanism. Adrenergic pathways do not participate in
      food-stimulated PYY release; however, electrical stimulation of the splanchnic
      nerves increased basal levels of PYY, suggesting that the sympathetic nervous
      system affects release of PYY.

PMID- 8278625
TI  - Glucocorticoids and the renal Na-H antiporter: role in respiratory acidosis.
AB  - We examined the role of glucocorticoids in the activity of the renal brush border
      Na-H antiporter under baseline conditions (5% CO2 gassing) and during respiratory
      acidosis (10% CO2 gassing) in cultured monolayers of a proximal tubule suspension
      (primary cultures of the proximal tubule). Primary cultures of the proximal
      tubule showed an adaptive increase in renal brush border Na-H antiporter activity
      in response to respiratory acidosis in presence but not in the absence of
      physiologic concentrations of hydrocortisone in the medium. The effect of
      hydrocortisone to increase the activity of the renal brush border Na-H antiporter
      in respiratory acidosis could also be elicited by dexamethasone. Deletion of
      hydrocortisone from the medium also impaired the baseline activity of the Na-H
      antiporter. The effect of hydrocortisone to increase the activity of the Na-H
      antiporter under baseline conditions and during respiratory acidosis was elicited
      by physiologic concentrations of the hormone and 100-fold increase in
      concentration did not further increase the activity of the Na-H antiporter. These
      results demonstrate that the presence of physiologic concentrations of
      glucocorticoids are necessary for the baseline activity of the renal brush border
      Na-H antiporter and its adaptive increase in response to respiratory acidosis.

PMID- 8278626
TI  - Decreased vasoactive intestinal polypeptide-immunoreactivity of parasympathetic
      neurons and target innervation following long-term sympathectomy.
AB  - Following long-term sympathectomy, parasympathetic neurons show increased
      expression of some catecholaminergic traits. The objective of this study was to
      determine if, in addition, expression of vasoactive intestinal polypeptide
      immunoreactivity (VIP-ir) is suppressed in parasympathetic neurons and a
      glandular target of the rat. Studies were conducted on the rat pterygopalatine
      ganglion and meibomian gland; the meibomian gland contains dense innervation that
      is strongly VIP-ir, and 99% of the VIP-ir neurons projecting to this target
      reside within the pterygopalatine ganglion. Two months following unilateral
      superior cervical ganglionectomy on postnatal day 30, DBH-ir fibers normally
      present within the eyelid were absent and there was a marked reduction in number
      and staining intensity of VIP-ir fibers within the meibomian gland. The
      percentage of pterygopalatine ganglion neurons displaying DBH-ir was increased
      from 43 +/- 4 to 65 +/- 2%. However, the percentage of parasympathetic neurons
      expressing VIP-ir was decreased from 96 +/- 4% to 76 +/- 1%. We conclude that
      sympathectomy not only enhances expression of some catecholaminergic traits but
      also suppresses VIP-ir within pterygopalatine ganglion parasympathetic neurons
      and meibomian gland target.

PMID- 8278627
TI  - Stimulation by vasoactive intestinal peptide (VIP) of phagocytic function in rat
      macrophages. Protein kinase C involvement.
AB  - The action of vasoactive intestinal peptide (VIP) on macrophages has not yet been
      studied, although there are studies that show an inhibitory action of VIP on
      lymphocyte functions. The present study shows that VIP in a range from 10(-12) to
      10(-7) M increased significantly the phagocytosis and digestion capacities of rat
      peritoneal macrophages. The most effective concentration of VIP was 10(-9) M
      followed by 10(-8) M. With respect to the phagocytic capacity, the ingestion of
      cells (Candida albicans) or inert particles (latex beads) was stimulated
      significantly with all the concentrations used. The digestion capacity was
      analyzed through the production of superoxide anion, measured by the reduction of
      nitroblue tetrazolium (NBT). As with phagocytic capacity, superoxide anion
      production was increased by VIP in non-stimulated macrophages (incubated without
      latex beads) and even more in stimulated cells (incubated in the presence of
      latex beads). The study of the mechanism of action of this neuropeptide showed
      that protein kinase C (PKC) was activated in the presence of VIP concentrations
      from 10(-10) to 10(-8) M in a similar way to that found with a specific PKC
      activator such as phorbol myristate acetate (PMA, 50 ng/ml). PMA also stimulated
      significantly the phagocytosis and digestion capacities of rat macrophages. By
      contrast, a PKC inhibitor, retinal (20 microM), decreased significantly the
      phagocytosis and digestion capacities. These data show that VIP could stimulate
      these macrophage functions through PKC activation.

PMID- 8278628
TI  - Opioid peptide release evoked by noxious stimulation of the hind instep of rats.
AB  - Previous studies showed that opioids and opioid peptides modulate vascular
      reactions such as plasma extravasation and vasodilatation through inhibition of
      substance P release from peripheral nerve endings of primary afferent fibers, and
      suggested the existence of endogenous opioid peptide activity related to
      regulation of inflammatory responses. Here we examined the effect of heat
      stimulation and antidromic stimulation of primary afferent fibers on the release
      of immunoreactive opioid peptides into the perfusate of the subcutaneous space in
      the rat instep. Antidromic stimulation of sectioned sciatic and saphenous nerves
      did not have any significant effect on the release of Met-enkephalin (Met-EK),
      while immersion of the hind paw in hot water (47 degrees C) for 30 min caused an
      increase in Met-EK release into the perfusate. High-pressure liquid
      chromatography of the perfusate revealed that noxious heat stimulation induced
      increase in release of Leu-enkephalin (Leu-EK) as well as Met-EK, although the
      maximal concentration of Leu-EK was less than 16% of that of Met-EK. No beta
      endorphin was detected in the perfusate before, during or after heating. We
      conclude that noxious heat stimulation mainly leads to increase in Met-EK, and
      that this peptide originates mainly, from peripheral cells containing opioid
      peptides such as immune cells and/or Merkel cells, not from primary afferent
      fibers.

PMID- 8278629
TI  - Plasma concentrations of arginine vasopressin, oxytocin and angiotensin in
      patients with hymenoptera venom anaphylaxis.
AB  - The plasma concentrations of arginine vasopressin, oxytocin, angiotensin I and II
      were studied in patients with hymenoptera venom anaphylaxis (n = 50) and healthy
      volunteers (n = 25). There was no difference in arginine vasopressin: 5.52 +/-
      0.45 fmol/ml vs. 3.99 +/- 0.41 fmol/ml or oxytocin: 28.10 +/- 1.13 fmol/ml vs.
      26.24 +/- 1.80 fmol/ml between patients and controls. No correlation between the
      severity of clinical symptoms and the plasma levels of arginine vasopressin and
      oxytocin was found in patients. However, patients with a history of hymenoptera
      venom anaphylaxis showed significantly reduced angiotensin I and angiotensin II
      plasma levels as compared to controls (ANG I: 9.51 +/- 0.61 fmol/ml vs. 22.91 +/-
      1.73 fmol/ml; ANG II: 2.84 +/- 0.16 fmol/ml vs. 6.95 +/- 0.33 fmol/ml). A
      significant inverse correlation between the severity of clinical symptoms and the
      plasma levels of angiotensin I and angiotensin II was observed; the lower the
      concentrations the more severe the clinical symptoms. Oxytocin immunoreactivity
      eluted from the HPLC column as a single peak with the same retention time as
      synthetic oxytocin. The vasopressin immunoreactive material could be
      characterized on HPLC as arginine-vasopressin and two other peptides of unknown
      nature which crossreacted with the vasopressin antibody. These findings suggest a
      possible role of angiotensin I and angiotensin II in hymenoptera venom
      anaphylaxis while arginine vasopressin and oxytocin are most likely not involved.

PMID- 8278630
TI  - Pituitary adenylate cyclase activating polypeptide (PACAP)-like immunoreactivity
      in ganglioneuroblastoma and neuroblastoma.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a 38 amino acid
      peptide originally isolated from ovine hypothalamus. It has a potent stimulatory
      action on adenylate cyclase in the rat pituitary. The presence of PACAP was
      studied in the tumor tissues of ganglioneuroblastoma and neuroblastoma by
      radioimmunoassay and immunocytochemistry. Immunocytochemical studies showed
      positive immunostaining in 4 out of 7 ganglioneuroblastomas and 4 out of 6
      neuroblastomas. Immunoreactive PACAP concentrations in tissues of 3
      ganglioneuroblastomas ranged from 14.5 to 27.8 pmol/g wet weight (20.0 +/- 5.7
      pmol/g wet weight, mean +/- S.D.) and the concentration in one neuroblastoma
      tissue was 111.0 pmol/g wet weight. Reverse phase high performance liquid
      chromatography of the tumor tissue extract of ganglioneuroblastoma showed a peak
      eluting in the position of PACAP1-38 and smaller broad peaks eluting later. These
      results indicated that high concentrations of immunoreactive PACAP were present
      in the tumor tissues of ganglioneuroblastoma and neuroblastoma, and suggest the
      possibility that this peptide plays a pathophysiological role in some
      ganglioneuroblastomas and neuroblastomas.

PMID- 8278631
TI  - Purification and amino acid sequence of motilin from cat small intestine.
AB  - Motilin was isolated from cat small intestine by a series of chromatographic
      steps. Using a radioreceptor assay, based upon binding of iodinated porcine
      motilin to rabbit antral smooth muscle membranes, it was shown that cat duodenal
      mucosa contains about 495 ng/g tissue, the jejunal mucosa 161 ng/g tissue and the
      ileal mucosa 95 ng/g tissue motilin. The duodenal mucosa was extracted with 6%
      acetic acid and concentrated on a cation exchange Whatman CM-52 gel. After
      lyophilization the material was further purified by gel filtration (Sephadex G
      50), followed by reverse phase (C18), cation exchange HPLC (Mono S) and three
      runs on a reverse phase HPLC (Nucleosil 300-5C18) column. The UV absorbance and
      the radioreceptor assay were used to monitor the purification. After Mono S
      chromatography two forms of motilin were detected. The major peak corresponded to
      a 22 amino acid peptide, which differed only from canine motilin at position 12,
      where Lys is replaced by Arg. The smaller peak probably corresponds to a
      deamidated form of this peptide. The sequence homology between cat and
      porcine/human motilin or cat and rabbit motilin is 81.8% and 72.7%, respectively.
      The conservation of the first six amino acids in all five species studied is
      striking, confirming that the biological activity of the peptide resides in the N
      terminal part.

PMID- 8278632
TI  - The lung contents of endothelin are altered by thyroid hormone status in rat.
AB  - Endothelin-1 (ET-1) is a 21-residue peptide isolated from the conditioned medium
      of cultured porcine endothelial cells and is widely distributed throughout the
      body, with relatively high levels in the kidney and lung. Animal studies have
      revealed that the lung appears to have the largest capacity for ET-1 removal from
      the blood stream. In this study we have examined the possible influence of
      thyroid status on immunoreactive endothelin (IR-ET) levels in the plasma and lung
      of the male rats. 3 weeks after the surgical removal of the thyroid gland from
      male rats, the IR-ET levels in the lung were reduced by 39%. Similarly, IR-ET
      levels were decreased 46% in the lung of rats rendered hypothyroid by treatment
      with 0.1% (w/w) PTU in the drinking water for 30 days, and replacement with daily
      L-thyroxine (T4) injections (5 micrograms/100 g) prevented this decrease.
      However, thyrotoxicosis induced by daily L-T4 injections (10 micrograms/100 g)
      also caused a decrease of the lung IR-ET levels by 49%. Nevertheless, the plasma
      IR-ET levels are similar in each group. Fast protein liquid chromatography study
      verified the presence of ET-1 immunoreactivity in both rat plasma and lung tissue
      extracts. This study demonstrates that euthyroid status is required for the
      maintenance of physiological concentrations of IR-ET in the lung of male rats.

PMID- 8278633
TI  - Effect of antrectomy and drug-induced achlorhydria on urinary excretion of N
      terminal big gastrin immunoreactivity in rats.
AB  - Immunoreactivities of urinary N-terminal big gastrin and serum C-terminal gastrin
      were determined in intact and antrectomized rats by radioimmunoassay using two
      antisera specific for N- and C-termini of big gastrin, respectively. Gel
      filtration of urine extract from intact rat showed a single giant peak of N
      terminal big gastrin immunoreactivity eluted in a later position than 1-17
      gastrin-34, indicating that N-terminal peptides smaller than 1-17 gastrin-34 are
      excreted in urine. Serum C-terminal gastrin concentration in antrectomized rats
      was about one sixth that in intact rats. Urinary excretion of N-terminal big
      gastrin in antrectomized rats was about one sixth that in intact rats. 2 week
      treatment with E3810, a proton pump inhibitor, (40 mg/kg/day, s.c.) induced
      urinary excretion of N-terminal big gastrin in parallel with a marked increase in
      serum C-terminal gastrin concentration in intact rats. Antrectomy completely
      prevented both the increase in urinary excretion of N-terminal big gastrin and
      the elevation of serum C-terminal gastrin induced by administration of E3810.
      There was an excellent correlation between serum concentration of C-terminal
      gastrin and urinary excretion of N-terminal big gastrin. These results suggest
      that urinary N-terminal big gastrin, which mostly originates from the gastric
      antrum, is a useful indicator of gastrin secretion in the rat.

PMID- 8278634
TI  - Role of GABA and opioids in the regulation of the vasopressin response to
      physical exercise in normal men.
AB  - The present study was undertaken in order to establish the possible involvement
      of GABAergic and/or opioid pathways in the mechanism underlying the arginine
      vasopressin (AVP) response to physical exercise. After fasting overnight, seven
      subjects were tested on four mornings at least 1 week apart. Exercise was
      performed on a bicycle ergometer. The workload was gradually increased at 3 min
      intervals until exhaustion and lasted about 15 min in all subjects. Tests were
      carried out under administration of placebo, the opioid antagonist naloxone (10
      mg as an i.v. bolus injection), the GABAergic agonist sodium valproate (600 mg in
      three divided doses orally) or naloxone plus sodium valproate. Plasma AVP levels
      rose 4-fold during exercise. The administration of naloxone did not modify,
      whereas sodium valproate completely abolished the plasma AVP rise during
      exercise. When naloxone was given together with sodium valproate, AVP rose 3-fold
      in response to exercise. These data suggest the involvement of a GABAergic
      mechanism in regulation of the AVP response to physical exercise in men.
      Furthermore, the data argue against a role of naloxone sensitive endogenous
      opioids in the control of AVP during exercise, whereas they suggest a partial
      opioid mediation of the GABAergic inhibitory action.

PMID- 8278635
TI  - Characterization of a calcitonin gene-related peptide (CGRP) receptor on mouse
      bone marrow cells.
AB  - Calcitonin gene-related peptide, (CGRP), a vasoactive neuropeptide, is found
      throughout the peripheral nervous system, and CGRP receptors are present on
      mature lymphocytes. The current studies describe a CGRP receptor on isolated
      mouse bone marrow cells. The affinity, distribution and specificity of CGRP
      receptors were analyzed using radioligand binding assays. [125I]CGRP binding in
      mouse bone marrow cells was dependent on cell concentration and was stable from 5
      to 60 min at room temperature. The average Kd is 3.29 +/- 1.24 nM and the average
      receptor density is 2796 +/- 365 sites/cell. Competition binding analysis found
      rat alpha and beta CGRP to be the most inhibitory, (Ki values 0.899 and 0.711 nM,
      respectively), followed by human alpha CGRP and the antagonist human CGRP8-37.
      The neuropeptides human and salmon calcitonin did not inhibit [125I]CGRP binding
      to bone marrow cells. The presence of CGRP receptors on mouse bone marrow cells
      provides further evidence for a direct role for CGRP in modulating the function
      and differentiation of cellular components of the immune and inflammatory
      systems.

PMID- 8278636
TI  - Microdialysis in the estimation of interstitial myocardial neuropeptide Y
      release.
AB  - The purpose of this study was to investigate the feasibility of cardiac
      microdialysis for the in vivo estimation of cardiac interstitial peptide
      concentrations, and, to determine the changes in neuropeptide Y release in
      myocardial tissue during experimental brain death in pigs. Using a specifically
      designed concentric flexible probe, perfused with Ringer solution containing 0.5%
      of bovine serum albumin at a flow rate of 2 microliters/min, allowed us to obtain
      a 23 +/- 2% relative recovery rate in vitro. Based on these in vitro recovery
      data, a regional study of the kinetics of interstitial NPY levels following brain
      death was obtained by monitoring the changes in NPY dialysate levels recorded
      from dialysis probes implanted into the right and left ventricular walls of the
      beating heart in vivo. Basal dialysate NPY levels determined by radioimmunoassay
      were of 95.2 +/- 7.0 and 93.2 +/- 9.1 pmol/l in left and right ventricle,
      respectively. Brain death was followed by a sustained 2 h increase in NPY
      dialysate levels in both ventricles (peak levels: 173.2 +/- 30.9 pmol/l in left
      ventricle, and 149.7 +/- 23.9 pmol/l in right ventricle), which then returned to
      control levels. We conclude that cardiac microdialysis is a simple and promising
      new tool for evaluating the role of peptides in cardiovascular regulation.

PMID- 8278637
TI  - Have animal data been used inappropriately to estimate risks to humans from
      environmental trichloroethylene?
AB  - Trichloroethylene (TCE) is widely viewed as an environmental hazard. Its major
      metabolite, chloral hydrate, is a currently used medicine. Regulation of TCE is
      based on a linear extrapolation from effects of high doses in rodents to risks
      for humans at low doses. However, metabolic, toxicologic, and epidemiologic data
      on trichloroethylene and chloral hydrate as well as water chlorination studies
      call this approach into question. The mechanism of carcinogenesis of TCE and
      chloral hydrate in rodents is nonlinear: very high doses, sufficient to cause
      cellular necrosis, are necessary. Malignancy arises from repeated cycles of
      necrosis and regeneration with the ultimate emergence of hyperplasia and then
      neoplasia. Metabolites of TCE, trichloroacetic acid and dichloroacetic acid,
      mediate this toxic effect of TCE. These chloroacetic acids also induce similar
      lesions in rodents given high doses of the medicine, chloral hydrate. Human
      epidemiologic data show no increase in mortality or malignancy from substantial
      chronic exposure to trichloroethylene. Chlorination of drinking water produces
      much higher levels of chloroacetic acids than could be obtained from metabolizing
      TCE under current regulations. We conclude that the assumptions underlying
      current regulations are not applicable to TCE. Instead of a straight-line
      extrapolation model, a threshold model may be more appropriate. The data suggest
      that it is possible to increase substantially the allowable trichloroethylene in
      drinking water without increasing health hazards.

PMID- 8278638
TI  - Confounded carcinogenicity study of sodium fluoride in CD-1 mice.
AB  - To determine its carcinogenic potential, sodium fluoride (NaF) was fed to CD-1
      mice for up to 97 weeks. Mice given NaF at a dose of 4, 10, or 25 mg/kg of body
      weight per day added to a low-fluoride diet were compared to controls given
      either an unsupplemented low-fluoride diet or laboratory chow. Nonneoplastic
      changes consistent with those previously recognized from fluoride toxicity were
      observed in teeth, bones, and joints. Unexpectedly, osteomas occurred in all
      groups. The incidence of osteomas was similar in groups given the low-fluoride
      control diet, laboratory chow, or NaF doses of 4 or 10 mg/kg per day. The
      incidence of osteomas in these groups was increased over that historically
      experienced at the laboratory and reported in the literature for CD-1 mice. The
      incidence of osteomas in the mice given 25 mg NaF/kg per day added to a low
      fluoride diet was increased over that in the other groups. Osteomas were first
      observed at Week 55. No malignant bone tumors were observed during the course of
      the study. The locations, multiplicity, and morphologic features of the osteomas
      in all groups were similar to those associated with virus-induced bone tumors.
      Electron microscopic examination revealed abundant retrovirus particles in all
      osteomas examined from control and test mice. It was concluded that the study was
      confounded by a retrovirus which contributed to the induction of the osteomas.
      Because the study was confounded, it cannot be considered a valid bioassay to be
      used for risk assessment.

PMID- 8278639
TI  - Critique of the toxicology and carcinogenesis studies of iodinated glycerol in
      F344/N rats and B6C3F1 mice.
AB  - Carter-Wallace conducted a detailed audit and evaluation of the data available
      from the carcinogenicity studies with iodinated glycerol conducted in the B6C3F1
      mouse and the F344/N rat by the National Toxicology Program (NTP). We conclude
      that there is no evidence of carcinogenicity of the compound in either the B6C3F1
      mouse or the F344/N rat.

PMID- 8278640
TI  - Documenting temporal trends of polychlorinated biphenyls in the environment.
AB  - In the 15 years since the regulation of polychlorinated biphenyls (PCBs) in the
      United States, numerous studies have been undertaken to assess PCB levels in the
      environment. This report reviews the available data from published literature and
      government agency reports on temporal trends of PCB levels in various
      environmental compartments. Adequate data were identified to discuss PCB trends
      in foods for human consumption, human adipose tissue, human blood sera, various
      fish species, and shellfish. The review found that PCB levels in the human diet
      currently are less than 1% of the levels detected in the early 1970s as measured
      by the nationwide Total Diet Study of the FDA. Similarly, EPA data indicate a
      decrease in the percentage of persons with over 1 ppm of PCBs in adipose tissue
      from 62% in 1972 to 2% in 1984 when the study was terminated. Studies by the
      National Oceanic and Atmospheric Administration (NOAA) and other groups have
      shown a 2- to 10-fold decline in PCB contamination in fish and shellfish from the
      early 1970s to the late 1980s. The most dramatic declines across all
      environmental compartments appear in the late 1970s to the mid-1980s which
      corresponds to the time frame when regulatory controls were imposed by the Toxic
      Substances Control Act (TSCA). These declines are expected to continue but at
      slower rates.

PMID- 8278641
TI  - Carcinogenicity of insulation wools: further comments and some new data.

PMID- 8278642
TI  - Reduction of animal use with improved procedure for acute tolerance assessment.
AB  - A retrospective evaluation of previously conducted acute tolerance tests in rats
      and mice, following oral and intravenous routes of administration, and a review
      of the literature indicated that a minimum of three animals per group was
      adequate to characterize acute tolerance. Limited exploratory testing, using six
      compounds for which classical LD50 tests had been performed previously, indicated
      that fewer numbers of rats gave comparable results. A method is proposed by which
      the acute tolerance of a compound may be adequately characterized in both sexes
      using approximately 30 animals instead of the 70 to 100 used in the classical
      LD50 test. The objective of the testing procedure is identification of the
      maximum nonlethal dose or the minimum lethal dose, rather than determination of
      the LD50.

PMID- 8278643
TI  - Comparison of cancer risks projected from animal bioassays to epidemiologic
      studies of acrylonitrile-exposed workers.
AB  - Bioassay findings have demonstrated that acrylonitrile (ACN) is a rodent
      carcinogen, but the available epidemiologic evidence provides little support for
      the human carcinogenicity of ACN. This discordance between laboratory animal and
      human study findings is explored by determining post hoc the statistical power of
      11 epidemiologic studies of ACN-exposed workers to detect the all-site and brain
      cancer excesses that are projected from rodent drinking water bioassay data. At
      reasonable estimates of the level and duration of exposures among the
      occupational cohorts, a majority of the human studies had sufficient power (>
      80%) to detect the projected excesses, yet such responses were consistently
      absent. We conclude, subject to certain caveats, that the upper bound estimate of
      ACN's inhalation cancer potency of 1.5 x 10(-4) per ppm is too high to be
      consistent with the human ACN experience.

PMID- 8278644
TI  - Logistic regression of inhalation toxicities of perchloroethylene--application in
      noncancer risk assessment.
AB  - Unlike the impressive advancement of cancer risk assessment, the "cutoff
      approach" based on hazard quotient in noncancer risk assessments recommended by
      the EPA has crucial deficiencies. Several alternative approaches have been
      suggested in the literature to modify the noncancer risk characterization based
      on reference doses. Recent studies have indicated that the effects of
      perchloroethylene (PERC) on the central nervous system (CNS) is a much more
      sensitive noncancer endpoint than cancer which is currently the basis for
      deriving its public health criteria and standards. Studies indicate that 20 ppm
      of inhaled PERC concentration elicited adverse effects on the CNS in experimental
      animals and humans. However, the existing EPA oral reference dose (RfD), a
      noncancer toxicity parameter for PERC (0.01 mg/kg/day), is based on the induction
      of hepatotoxicity and increased body weight gain induced by PERC in rats. An
      attempt was made in this paper to examine whether logistic regression of dose
      response data could be applied to assess the noncancer risks. In order to perform
      logistic regression the inhalation toxicity data of PERC were classified
      according to the severity of toxicity paradigm used in toxicity analysis. Based
      on the sensitive noncancer endpoints identified from severity classification, a
      logistic regression analysis of the data was performed and its potential
      applicability in noncancer risk characterization was described for workers
      exposure to PERC in dry-cleaning operations.

PMID- 8278645
TI  - Some toxicological issues in chemical safety and regulation in an Australian
      context.
AB  - This article considers the potential effects on the human body of toxic hazardous
      substances in general, along with advanced methods of detecting short- and long
      term effects of exposure with reference to the results of recent research. In
      addition to occupational exposure, other contributors to an individual's overall
      toxic exposure load including environmental and home and lifestyle exposures are
      also considered in detail. Toxicological information (from diverse sources) and
      an awareness of the limitations of our present state of knowledge of toxicology
      are concluded to be important factors in developing chemical safety and
      regulatory criteria. Although there is some debate concerning the adequacy of the
      exposure standard-setting process, TWA measures are capable of giving reliable
      indications of the efficacy of control measures and procedures.
      Electroencephalogram (EEG) activity reflecting stimulus attention and decision
      time, electromyography measuring nerve conduction velocities, reaction time, and
      neuropsychological performance-using batteries of psychometric tests, may all be
      effective indicators of exposure, interaction with other factors, and long-term
      effects of exposure.

PMID- 8278646
TI  - Rising lung cancer mortality in the United States, 1968-1988: the manifestation
      of altered disease competition.
AB  - Lung cancer mortality is increasing. The strong association between cigarette
      smoking and lung cancer is universally acknowledged. Consequently, rising lung
      cancer mortality is commonly attributed to cigarette smoking. This chain of logic
      has resulted in a remarkable evolution of public attitudes toward cigarette
      smoking and in increased regulation of smoking at work and in public places.
      However, longitudinal Gompertzian analysis indicates that the major force
      increasing lung cancer mortality in the United States is the declining
      competitiveness of other causes of death, particularly ischemic heart disease and
      stroke. Indeed, this analysis demonstrates that the "environmental" influence
      upon lung cancer mortality began to decline in the United States in the mid
      1970s, supporting the effectiveness of programs aimed at decreasing tobacco use.

PMID- 8278647
TI  - Comparing the results of a Monte Carlo analysis with EPA's reasonable maximum
      exposed individual (RMEI): a case study of a former wood treatment site.
AB  - In the United States, there are about 250 former sites that treated wood with
      preservatives that are now in need of some degree of remediation. The soil at
      many of these sites is contaminated with creosote, polycyclic aromatic
      hydrocarbons (PAHs), polychlorinated dibenzo-p-dioxins (PCDDs), and
      polychlorinated dibenzofurans (PCDFs). This paper compares the results of the
      current USEPA point estimate (deterministic) approach for predicting the health
      risks associated with exposure to PCDDs/PCDFs in soil with the results of a
      probabilistic approach which uses a Monte Carlo analysis. At many of these wood
      treatment sites the hazard posed by the PAHs, and especially pentachlorophenol,
      can be much greater than that due to PCDD and PCDFs; however, because at this
      site the health risk associated with PAHs was deemed negligible by ATSDR, only
      PCDDs/PCDFs were evaluated. Octachlorodibenzo-p-dioxin (OCDD) and
      octachlorodibenzofuran (OCDF) congeners were evaluated independently from the
      other congeners due to their prevalence in the environment and the availability
      of congener-specific data. The results of the reevaluation of the rodent bioassay
      data for 2,3,7,8-TCDD were considered in the probability distribution for the
      cancer potency factor. The authors' analyses indicate that when assessing
      exposure to soil via inhalation, ingestion, and dermal contact, the current
      regulatory approach used to estimate the reasonable maximally exposed individual
      (RMEI) (USEPA, Risk Assessment Guidance for Superfund, Vol. 1, Part A, 1989) can
      predict risks which are 10- to 100-fold greater than the 95th percentile risk
      predicted by a Monte Carlo analysis.

PMID- 8278648
TI  - Scientific principles for evaluating the potential for adverse effects from
      chlorinated organic chemicals in the environment.
AB  - The term chlorinated chemicals is used to describe diverse groups of chemicals of
      varying chemical structure, including those used in water disinfection, as well
      as numerous aliphatic, aromatic, and polycyclic chlorinated substances. This
      report elaborates a number of scientific principles that govern the evaluation of
      the potential for chlorinated organic chemicals to cause adverse effects on the
      environment and to human health. The purpose of the report is to demonstrate the
      importance of applying these scientific principles in the evaluation of potential
      adverse effects of chlorinated organic chemicals. The four major principles upon
      which such a scientific analysis must be based are: (1) the fate and biological
      activity of a compound are determined by the chemical properties of the compound;
      (2) compounds do not show adverse effects below certain threshold concentrations,
      and the magnitude of response is related to dose; (3) inherent metabolic
      processes allow organisms to accommodate low doses of chlorinated organic
      chemicals; (4) observations associated with the presence of a certain compound
      must be biologically plausible effects, based on the specificity of the
      compound's activity in experimental systems. With respect to the first of these
      principles, there is abundant scientific evidence that the physical and chemical
      properties of chlorinated organic chemicals govern their bioaccumulative
      potential, toxicological properties, and thus their potential behavior and
      effects in the environment. Chemicals that have low solubility in water are
      highly lipophilic and have low vapor pressure, tend to accumulate in biological
      systems, and degrade slowly in the environment. Chlorinated organic chemicals
      that possess these characteristics include those having a carbon ring structure
      and multiple chlorine substitution. Other chlorinated organic chemicals with
      lesser degrees of chlorine substitution, such as 2,4-dichlorophenoxyacetic acid
      (2,4-D), trichlorophenol, chloroform, and dichloroethane, do not share the
      physical and chemical properties of the high molecular weight, cyclic,
      polychlorinated compounds and, as such, do not have the same potential to
      bioaccumulate. These differences among chlorinated organic chemicals with respect
      to their physical and chemical properties and behavior in the environment
      preclude the generalization that all organic chemicals containing chlorine behave
      similarly in the environment and act as persistent, bioaccumulative chemicals.
      The reactivity of chlorinated organic chemicals and hence their potential to
      produce biological effects depends on their specific molecular features. The
      substitution of chlorine into an organic molecule may increase or may reduce its
      biological activity.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8278649
TI  - The nutritional assessment of novel foods and processes. Panel on Novel Foods of
      the Committee on Medical Aspects of Food Policy.

PMID- 8278650
TI  - Abnormal T-cell costimulation by proteins of the extracellular matrix in human
      renal allografting.
AB  - T cells interact with extracellular matrix (ECM) proteins as they pass through
      the endothelium and move about in various microenvironments. Recent data indicate
      that such proteins provide strong costimulation to CD3-TCR-complex-mediated T
      cell activation. Thus, ECM proteins can regulate T-cell responses via their
      integrin and non-integrin receptors. We have shown that the costimulating
      activity of interstitial ECM proteins (collagen type I, fibronectin) is abolished
      in renal allograft recipients treated with cyclosporin A (CsA) but not
      azathioprine. In contrast, cyclosporin treatment does not affect potent
      costimulation provided by the major component of basement membranes, collagen
      type IV. We suggest that these disturbances in T-cell interactions with ECM
      proteins caused by CsA therapy may contribute to cyclosporin-induced transplant
      arteriosclerosis.

PMID- 8278651
TI  - Phagocytic activity in stressed mice: effects of alprazolam.
AB  - Mice exposed to a chronic auditory stressor and daily injected with alprazolam (1
      mg/kg/day, s.c.) showed a reduction in stress-induced suppression of the in vitro
      and in vivo activity of phagocytosis, measured using the zymosan particle uptake
      method and the carbon clearance test, respectively. Pretreatment with Ro-15-1788
      (10 mg/kg, s.c.), a central nervous system benzodiazepine antagonist, resulted in
      suppression of the effects of alprazolam in stressed mice.

PMID- 8278652
TI  - TNF and the pathology of the skin.

PMID- 8278653
TI  - Lung and gut injury induced by tumour necrosis factor.

PMID- 8278654
TI  - TNF-alpha and insulin-dependent diabetes mellitus.

PMID- 8278655
TI  - Probing the mechanism of TNF-alpha(cachectin)- and TNF-beta(lymphotoxin)-induced
      pancreatic inflammation with transgenic mice.

PMID- 8278656
TI  - Tumour necrosis factor: a specific trigger in arthritis.

PMID- 8278657
TI  - Haematologic effects of TNF.

PMID- 8278658
TI  - TNF in vascular pathology: the importance of platelet-endothelium interactions.

PMID- 8278659
TI  - The role of TNF in tumour growth and metastasis.

PMID- 8278660
TI  - A role for TNF during African trypanosomiasis: involvement in parasite control,
      immunosuppression and pathology.

PMID- 8278661
TI  - Role of TNF in immunopathology of leprosy.

PMID- 8278662
TI  - 1993 C.H. McCloy Research Lecture: physical activity, physical fitness, and
      health.

PMID- 8278663
TI  - The importance of physical fitness versus physical activity for coronary artery
      disease risk factors: a cross-sectional analysis.
AB  - Numerous epidemiological investigations have shown that low physical fitness and
      low physical activity are related to the incidence of coronary artery disease
      (CAD). Most studies, however, have not examined both variables concurrently to
      determine which has the strongest association with CAD risk. The purpose of this
      investigation was to cross-sectionally examine the relationships among physical
      fitness, physical activity, and risk factors for CAD. Male law enforcement
      officers (N = 412) from the City of Austin, Texas, were subjects for this study.
      Physical fitness, physical activity, and risk factors for CAD were assessed
      through health screenings and from data collected as part of an annual physical
      fitness assessment. Multivariate analysis of covariance revealed that physical
      fitness, but not physical activity, was related to several single CAD risk
      factors. Percent body fat, smoking habits, and Type A behavior score were
      negatively related to physical fitness level, and high density lipoprotein (HDL)
      cholesterol was positively related to physical fitness level. Univariate analysis
      of variance found both physical fitness and physical activity to be significantly
      related to a composite CAD risk score. Low physical fitness and low physical
      activity were associated with a high CAD risk score. These data suggest that
      physical activity must be sufficient to influence physical fitness before
      statistically significant risk-reducing benefits on single CAD risk factors are
      obtained, although minimal engagement in weekly vigorous activity provides a
      significant benefit for the composite CAD risk score. It is plausible, however,
      that physical fitness is a stronger measure than physical activity and optimally
      characterizes the relationship among physical activity and CAD risk factors.

PMID- 8278664
TI  - Ideokinetic imagery as a postural development technique.
AB  - In two experiments we examined the effectiveness of ideokinetic imagery and
      flexibility combined with abdominal strength training as methods for improving
      the spinal angles of lordosis and kyphosis and reducing low back pain.
      Ideokinetic imagery is a postural development technique that involves using
      movement images to gain subcortical control over the spinal musculature.
      Experiment 1 investigated the effectiveness of these treatments for males with a
      previous history of low back pain. Findings indicated that only ideokinetic
      imagery had a positive effect on the spinal column and low back pain. Experiment
      2 extended these findings by investigating males and females using a noninvasive
      video analysis technique to record changes in spinal angles. This study further
      supports the effectiveness of ideokinetic imagery as a postural development
      technique in males with acute spinal angles. In these subjects spinal angles
      improved significantly, and the subjects reported complete cessation of low back
      pain. This research supports the use of ideokinetic imagery as an inexpensive and
      noninvasive technique to improve poor posture and reduce low back pain.

PMID- 8278665
TI  - Children's self-regulated learning of movement sequences.
AB  - The purpose of this study was to determine whether developmental differences
      exist in childrens' use of self-regulatory strategies while learning supra-memory
      span movement sequences. Grade 1 and Grade 4 children were asked to study two
      movement sequences long enough to be absolutely certain that they would be able
      to recall the entire sequences correctly. The older group displayed superior
      recall readiness in comparison to the younger group. Older children used a
      greater variety of strategies and also displayed significantly greater numbers of
      strategy orchestration patterns. In addition, Grade 4 children more frequently
      used overt encoding and self-checking strategies. Further, evidence suggests that
      Grade 4 children used language to encode movement components or to regulate their
      own learning more frequently than Grade 1 children.

PMID- 8278666
TI  - Variance and invariance in expert and novice triple jumpers.
AB  - The purpose of this study was to examine relative timing, relative distance, and
      effector independence characteristics of the triple jump. We videotaped expert
      and novice triple jumpers using standing and running starts. On some trials, the
      triple jumpers were required to take off from their nondominant leg. Gentner's
      (1987) interaction test was used to assess the proportional duration model in
      describing the timing of the component submovements. For both experts and
      novices, the proportional durations varied with the type of start. For experts,
      the relative timing of the jump components was independent of the take-off leg.
      The findings were mixed for the novices. Similar results were obtained when
      relative distance was examined. These results are discussed with respect to
      constructs related to variability in skilled performance.

PMID- 8278667
TI  - Effects of traditional and reversed bandwidth knowledge of results on motor
      learning.
AB  - The effects of two types of bandwidth (BW) knowledge of results (KR) were
      investigated on the acquisition and immediate retention of a timing task.
      Traditional and reversed BW KR groups were compared with two yoked control
      groups. Forty-eight randomly assigned subjects completed 60 acquisition trials
      and 20 no-KR retention trials. Acquisition analysis indicated a greater timing
      accuracy for the traditional BW group in comparison to the reversed BW group.
      During retention, less absolute constant error was found for both BW groups than
      for their yoked controls. Absolute performance changes were analyzed to further
      differentiate the contributions of quantitative and qualitative KR available in
      both types of BW conditions. This analysis revealed a significant KR x Trial Type
      interaction. Reliable changes in performance were observed after quantitative
      trials for the traditional BW group, whereas for the reversed BW group, reliable
      changes were observed after qualitative trials. This reversed BW group finding,
      along with the retention accuracy findings, indicated that the qualitative
      information was used to learn the timing task.

PMID- 8278668
TI  - The impact of student goal orientation in physical education classes.
AB  - The theory of achievement motivation suggests that students whose goals are
      related to the mastery of a task are more likely to engage in adaptive patterns
      of behavior such as choosing challenging tasks and focusing on effort. Students
      whose goal orientations are ego-involved are more apt to avoid challenge and be
      unwilling to expend effort. The purpose of this study was to explore the impact
      that goal perspective has in physical education classes. Subjects (N = 90) were
      college students in beginning tennis classes. They completed a skill pretest and
      the Task and Ego Orientation in Sport Questionnaire (Duda, 1992). A system of
      contract grading was employed to yield an indication of students' selection of
      challenging tasks. The points earned toward the contracts were used as an
      indicant of in-class behavior. At the end of the semester, students completed a
      skill posttest and a cognitive processes questionnaire. A task-involved goal
      perspective was associated with the selection of more challenging tasks and
      positive scores on the questionnaire. Those two variables, in turn, were
      significant predictors of student achievement. The results suggest that goal
      perspective could be an important influence on students' thought and action in
      physical education classes.

PMID- 8278669
TI  - Students' constructs of elementary school physical education.
AB  - The constructivist educational orientation acknowledges that students construct
      their own learning as they experience and make meaning from their schooling. An
      elementary school physical education master teacher and 10 of her former students
      participated in a naturalistic study designed to answer two research questions:
      (a) How did 10 students at the time of their high school graduation construct the
      meaning of elementary school physical education? and (b) What factors associated
      with their elementary school physical education experiences influenced the ways
      they constructed meaning? Participants were asked to reminisce in a
      semistructured, open-ended interview format specifically designed to enhance the
      recall of their physical education experiences during the 7-year, K-6 time frame.
      Data were inductively analyzed using the constant comparative analytic strategy.
      The meanings constructed by the students from their elementary school physical
      education experiences were defined by the teacher's value orientation and her
      invitational teaching style. Gender was the only factor evidenced in influencing
      the construction of meaning, with females recalling more variety and greater
      detail in the sport curricular area.

PMID- 8278670
TI  - Domain specifications and content representativeness of the revised Value
      Orientation Inventory.
AB  - Value orientations represent theoretical belief systems that guide teachers'
      curricular decision making. Research using the Value Orientation Inventory (VOI)
      to examine physical educators' value orientations in school settings found
      inconsistencies between the inventory findings, descriptions of class
      environments, and teachers' self-reports of their curricular goals. This article
      reports the VOI revision process that included (a) literature and research
      reviews resulting in domain specifications and new VOI item development and (b)
      item ratings that provide evidence of content representativeness for the revised
      items. The reviews supported four of five orientations that formed the original
      theoretical framework for the VOI: disciplinary mastery, learning process, self
      actualization, and ecological integration. The fifth orientation, social
      reconstruction, was not supported by school-based research. Findings were more
      consistent with a social responsibility orientation. New items (K = 150) were
      written based on the literature reviews. The new items were sent to university
      and public school teachers (N = 298) to assess content representativeness. Eighty
      one percent of the item means were > 4.0 on a 5-point scale. The social
      responsibility items were found to be domain representative and were included in
      the revised inventory.

PMID- 8278671
TI  - Evaluation of relapse prevention and reinforcement interventions to promote
      exercise adherence in sedentary females.
AB  - An experimental design was employed to assess the effectiveness of a relapse
      prevention program, a reinforcement program, and an exercise-only control group
      in increasing exercise program adherence and short-term maintenance in 120
      previously sedentary female university employees. The subjects participated in an
      18-week exercise program composed of stretching, calisthenics, and aerobic dance.
      Attendance during the first half of the program was significantly higher for
      subjects in the relapse prevention group than for those in the control group. A
      nonsignificant trend in this direction emerged during the second half of the
      program and at 2-month follow-up. For all treatment groups, attrition (attendance
      at less than two thirds of the exercise sessions) was substantial, averaging 72%
      at the end of the 18-week program. These findings indicate that relapse
      prevention and reinforcement programs may not assist previously sedentary females
      in long-term adherence to an exercise program.

PMID- 8278672
TI  - Coping strategies used by national champion figure skaters.
AB  - This investigation had two purposes: (a) to identify and describe the coping
      strategies used by national champion figure skaters and (b) to examine the
      relationship between coping strategies and particular stress sources.
      Participants were 17 of 20 (85%) Senior U.S. National Champion figure skaters who
      won titles between 1985 and 1990. All skaters were interviewed, and the interview
      transcripts were content analyzed. General coping dimensions reported by at least
      40% of the skaters included (a) rational thinking and self-talk, (b) positive
      focus and orientation, (c) social support (e.g., receiving support from coach,
      talking with friends and family), (d) time management and prioritization, (e)
      precompetitive mental preparation and anxiety management (e.g., relaxation,
      visualization), (f) training hard and smart, (g) isolation and deflection (e.g.,
      not letting things get to me, avoiding/screening media), and (h) ignoring the
      stressor(s). It was also found that the skaters implemented different coping
      strategies depending on the specific stressors encountered.

PMID- 8278673
TI  - Effects of HMG-CoA reductase inhibitors on skeletal muscles of rabbits.
AB  - This study was undertaken to evaluate the potential of HMG-CoA reductase
      inhibitors, pravastatin sodium (hereafter abbreviated to pravastatin) and
      simvastatin, for induction of myopathy and influence on the ubiquinone content of
      skeletal and cardiac muscles and other tissues in the rabbit. Both drugs were
      administered orally to New Zealand White rabbits (n = 5) at the dose of 50 mg/kg
      per day for 14 days. Serum cholesterol levels in the pravastatin- and simvastatin
      treated groups were reduced significantly by 47% an 58% on day 14 (P < 0.05),
      respectively, as compared with the control group, but the difference between the
      two treatment groups was not significant. In animals of the simvastatin-treated
      group, abnormal elevations of creatine kinase (CK) and lactate dehydrogenase
      (LDH) levels were observed, in association with severe lesions in skeletal
      muscles, but not cardiac muscle. The ubiquinone content in skeletal muscle in
      this treatment group was not affected, even in the muscles that had severe
      lesions, whereas that in liver and cardiac muscle was significantly reduced
      compared with the control group. The results suggest that there is no direct
      correlation between myopathy and the decrease of ubiquinone content in skeletal
      muscles. In contrast, the animals in the pravastatin-treated group did not show
      any changes in CK and LDH levels, ubiquinone content in liver and muscles, or in
      histopathological features of muscle fibers. The difference between the adverse
      effects seen with the two drugs could be attributed to physicochemical
      properties: simvastatin permeates the plasma membrane because of its hydrophobic
      nature, whereas pravastatin does not, because it is hydrophilic.

PMID- 8278674
TI  - Normothermic liver ischemia in rats: xanthine oxidase is not the main source of
      oxygen free radicals.
AB  - We studied the effect of allopurinol (ALL) on the activity of xanthine
      dehydrogenase (XDH), xanthine oxidase (XOX), superoxide dismutase (SOD), and
      catalase (CAT) in rat liver during ischemia followed by 60 min of reperfusion. We
      induced 60-min ischemia in the median and left lobes by clamping the hepatic
      artery and portal branches. The percentage XOX relative to total oxidase activity
      increased significantly in the control group, from 10% during the stabilization
      period to 18% after 60 min of reperfusion. The XDH activity decreased during
      reperfusion. Activity of both XDH and XOX was almost completely blocked by ALL.
      The activity of SOD and CAT did not differ significantly between the ALL group
      and controls after 60 min of reperfusion. ALL treatment did not affect liver
      injury parameters, as concentrations of lactate dehydrogenase (LDH) and alanine
      transferase (ALT) increased in plasma after ischemia, both in controls and in the
      ALL-treated group. We concluded that ischemia promotes conversion of XDH to XOX
      during reperfusion. XOX may not be the main source of free radical production,
      since intracellular scavengers (SOD and CAT) did not differ significantly between
      controls and the ALL-treated group, despite the fact that ALL blocked XOX
      activity completely.

PMID- 8278675
TI  - Phospholipid impregnation of abdominal rubber drains: resistance to bacterial
      adherence but no effect on drain-induced bacterial translocation.
AB  - In order to evaluate the effect of surface modification of biomaterials on
      bacterial adherence and bacterial translocation after intraperitoneal biomaterial
      implantation, phosphatidylcholine- or phosphatidylinositol-impregnated rubber
      drain pieces, which had been intraperitoneally implanted in the rat for 2 and 7
      days, or unimplanted, were incubated in vitro with 3H-labelled Escherichia coli
      and Enterobacter cloacae. As compared with unimpregnated pieces, the adherence of
      bacteria significantly decreased to phosphatidylcholine- and phosphatidylinositol
      impregnated rubber drain pieces that were either unimplanted or implanted for 2
      days, but not for 7 days. The supplementation of albumin in the medium reduced
      the adherence of bacteria to the unimplanted, unimpregnated drain pieces, but did
      not further decrease adherence of bacteria to the unimplanted, phospholipid
      impregnated brain pieces. Bacterial growth was inhibited after incubation in
      nutrient broth supplemented with phospholipids. The incidence of enteric
      bacterial translocation induced by intraperitoneal drain implantation did not
      differ between phospholipid-impregnated and unimpregnated drain pieces. Scanning
      electron microscopy revealed a large amount of biofilm and fibrous deposition on
      the surface of the implanted, phospholipid-impregnated rubber drain pieces. Thus,
      phospholipid impregnation of rubber drains reduces bacterial adherence and
      inhibits bacterial growth, without influencing the incidence of bacterial
      translocation.

PMID- 8278676
TI  - Effects of TRH and high-dose corticosteroid therapy on evoked potentials, and
      tissue Na+,K+ and water content in experimental spinal injury.
AB  - The therapeutic effects of continuous infusion of thyrotropin-releasing hormone
      (TRH) and methylprednisolone (MP) in experimental spinal cord injury were studied
      in Swiss albino rats. Thirty rats received a 53-g clip-compression injury on the
      cord at T1, then were allocated randomly and blindly to one of three treatment
      groups (ten animals in each): (1) control; received equal volumes of saline
      solution; (2) MP; received 30 mg/kg methylprednisolone i.v. 1h after trauma,
      followed by infusion of 5.4 mg/kg/per hour i.v. for 3h; (3) TRH; received 2 mg/kg
      TRH i.v. 1h after trauma, followed by infusion of 1 mg/kg/per hour i.v. for 3h.
      MP and TRH treatments significantly improved somatosensory-evoked potentials
      (SEPs; P < 0.001). Both treatments significantly reduced water content, decreased
      Na+ content and increased the K+ content of the cord segment that included the
      centre of the impact (P < 0.01). Our data provide evidence for the beneficial
      effects of high-dose corticosteroid and TRH in promoting electrophysiological
      recovery and preserving spinal cord tissue following experimental injury.

PMID- 8278677
TI  - Influence of age on the cardiovascular response during graded haemorrhage in
      anaesthetized rats.
AB  - The present study was designed to follow the cardiovascular response to graded
      haemorrhage in two groups of adult rats of different ages. Group A (n = 10) had a
      mean body weight (bwt) of 655 g (50 weeks old) and group B (n = 10) had a mean
      bwt of 250 g (12 weeks old). After induction of anaesthesia, the carotid artery
      was cannulated for continuous intra-arterial blood pressure monitoring and for
      controlled haemorrhage. Five per cent of the total blood volume (TBV) was removed
      every 15 min until a maximum of 50% was reached. Mean arterial pressure (MAP)
      fell by 4-9 mm Hg each time 5% TBV was removed in both groups, and at the end of
      the study the MAP was comparable in the two groups (34 +/- 10 mm Hg in group A
      and 28 +/- 8 mm Hg in group B). There were no significant changes in heart rate
      (HR) in the young animals during haemorrhage, while there was a significant drop
      in heart rate in the older animals when blood loss exceeded 15% of TBV (P <
      0.05). A significant difference was also observed in HR between the two groups of
      animals with blood loss in excess of 20% TBV (P < 0.05). It was concluded that
      although the hypotension induced by graded haemorrhage was similar in young and
      old rats, the older animals were less able to maintain their HR, probably as a
      consequence of age- and anaesthetic-related changes in sympathetic activity.

PMID- 8278678
TI  - Bacterial pneumonia in HIV-infected patients.
AB  - Individuals infected with the human immunodeficiency virus (HIV) are more
      susceptible to bacterial infections because of defects in both cellular and
      humoral immunity. Streptococcus pneumoniae and Haemophilus influenzae are the
      most common causes of bacterial pneumonia in HIV-infected patients. However, more
      unusual bacteria can also cause pneumonia. Response to therapy is generally good
      for infections caused by pyogenic organisms, and complications are relatively
      few. Unfortunately, infections caused by Rhodococcus equi and Nocardia species
      are associated with significant morbidity and mortality. Moreover, the duration
      of therapy is long, and relapes are common. Prevention of bacterial pneumonia is
      an important part of the care of HIV-infected patients; the 23 valent
      pneumococcal vaccine is currently recommended for all HIV-infected patients. The
      role of other preventative measures remains unknown.

PMID- 8278679
TI  - Pulmonary fungal infections in HIV-infected persons.
AB  - Fungal infections account for a large number of AIDS-index diagnoses and
      complicate the course of most patients with HIV disease. Infection with
      Cryptococcus neoformans is the most commonly encountered deep-seated fungal
      infection in AIDS and represents a major threat to HIV-infected people worldwide.
      Although most patients with cryptococcosis present with meningitis, pulmonary
      disease may occasionally dominate the clinical picture. Treatment of symptomatic
      pulmonary cryptococcosis remains amphotericin-B with or without 5-flucytosine.
      The toxicity and difficulty of administration of amphotericin-B has engendered
      interest in treatment alternatives with the new triazoles. As HIV infection has
      become more common in the American heartland, it has overlapped areas endemic for
      Histoplasma capsulatum, Coccidioides immitis, and Blastomycosis dermatitidis.
      Disease from these deep-seated fungal pathogens, whether from de novo exposure or
      reactivation, has protean manifestations. Common to all is a protracted, febrile,
      wasting illness, with or without respiratory symptoms. Treatment of choice for
      all these infections remains amphotericin-B, followed by lifelong-maintenance
      therapy with a triazole. In this article I review the microbiology, epidemiology,
      presentation, diagnosis, and treatment of AIDS-associated deep-seated fungal
      infections.

PMID- 8278680
TI  - Mycobacterium avium complex and other nontuberculous mycobacterial infections in
      patients with HIV.
AB  - Since the beginning of the AIDS epidemic, nontuberculous mycobacterial infections
      have been reported with increasing frequency in HIV-infected patients. Although
      Mycobacterium avium complex has been responsible for the majority of these
      infections, an increasing number of other nontuberculous mycobacteria have been
      reported to cause clinical disease. In spite of initial questions about the
      clinical significance of disseminated M avium complex infection, it now appears
      that this infection contributes to the morbidity and mortality of HIV-infected
      patients. Therefore, recent studies have focused on the use of antimycobacterial
      drugs to treat or prevent M avium complex bacteremia. These studies have found
      that drug treatment, especially with the newer macrolides, can decrease
      bacteremic load and improve debilitating symptoms. Furthermore, rifabutin have
      been found to decrease or delay the development of M avium complex bacteremia. As
      HIV-infected patients live longer because of antiviral drugs or prophylaxis
      against opportunistic infections, nontuberculous mycobacterial infections will
      likely become increasingly frequent and contribute to substantial morbidity or
      mortality.

PMID- 8278681
TI  - Pulmonary manifestations of acquired immunodeficiency syndrome-associated
      malignancies.
AB  - Significant progress has been made in the treatment and prophylaxis of human
      immunodeficiency virus (HIV)-associated infections. As patients with HIV
      infection live longer, more cases with HIV-associated malignancies are being
      reported. Pulmonary complications of HIV-associated Kaposi's sarcoma and non
      Hodgkin's lymphoma present clinicians with diagnostic and therapeutic challenges.
      Pulmonary involvement with Kaposi's sarcoma ranges from 6% to 32%. Pulmonary
      involvement with acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin's
      lymphoma occurs in about 8% of cases. Symptomatic pulmonary involvement, although
      unusual, may necessitate aggressive intervention with chemotherapy or radiation
      therapy. Although survival benefit has not been seen with aggressive therapy,
      significant palliation of symptomatic disease has been noted. Other non-AIDS
      associated malignancies in HIV-infected patients, including Hodgkin's disease and
      bronchogenic carcinoma, have been reported in several series. Although no
      conclusive epidemiological data have yet linked HIV disease with the development
      of these malignancies, some investigators indicate that these cancers have an
      altered natural history in the HIV-infected patient. A more thorough
      understanding of the mechanisms by which HIV alters host immunity, predisposing
      the host to these malignancies, will afford new insight into ways to treat these
      life-threatening complications of HIV disease.

PMID- 8278682
TI  - Update: HIV infection and pulmonary host defenses.
AB  - Infection with the human immunodeficiency virus (HIV) produces profound
      alterations in host defense mechanisms throughout the respiratory tract. The
      extent of alteration of specific defenses varies with the stage or duration of
      HIV infection in the host. In the upper respiratory tract, HIV-infected
      individuals have decreased concentrations of salivary immunoglobulin A, which may
      predispose to colonization of the oropharynx with pathogenic microorganisms. In
      the lower respiratory tract, host defenses are provided by alveolar macrophages,
      lymphocytes, and polymorphonuclear leukocytes. Alveolar macrophages can be
      chronically infected with HIV, and demonstrate a number of compromised host
      defense functions. The HIV-infected host has a limited capacity to generate
      soluble signals necessary for activation of alveolar macrophages for microbial
      killing. CD4 lymphocytes, which are quantitatively depleted during HIV infection,
      also demonstrate qualitative defects. Proliferation of CD8 lymphocytes, directed
      against HIV-infected cells in the lung, is associated with the noninfectious
      pulmonary complications of acquired immunodeficiency syndrome. B lymphocytes from
      HIV-infected persons show deficient production of opsonizing antibodies, which
      may predispose to bacterial pneumonias. Defective responses of polymorphonuclear
      leukocytes in the lung are also likely to contribute to impaired host responses.
      Collectively, these multiple defects in the defense mechanisms of the respiratory
      tract explain the unique susceptibility of the HIV-infected host for
      opportunistic pulmonary infections.

PMID- 8278683
TI  - Update on laboratory tests for the diagnosis of pulmonary disease in HIV-1
      infected individuals.
AB  - Various diagnostic tests, both specific and nonspecific, are available in the
      clinical laboratories for diagnosing human immunodeficiency virus-1 (HIV-1)
      infection and associated respiratory pathogens. Pneumocystis carinii pneumonia
      remains the most common pulmonary disease in HIV-1-infected individuals and there
      have been no significant advances in the laboratory diagnosis of the pathogen
      beyond the traditional microscopic examination of specimens. In contrast, the
      greatest revolution in laboratory diagnostic testing has been for mycobacteria,
      with major advances resulting in significant reduction in the time necessary for
      isolation and identification to the species level. The application of the
      polymerase chain reaction for the identification of a variety of pulmonary
      pathogens observed in HIV-1 infected individuals is discussed.

PMID- 8278684
TI  - Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency
      syndrome.
AB  - Pneumocystis carinii infection remains extremely common in the immunocompromised
      patient population, particularly in patients with human immunodeficiency virus
      (HIV) infection, despite the availability of effective prophylaxis. Although most
      commonly presenting as an acute pneumonia, the organism can infect a multitude of
      different organs, and thus may pose difficulty in diagnosis. Because effective
      treatment regimens such as trimethoprim-sulfamethoxazole (TMP-SMX) and parenteral
      pentamidine are hindered by a high rate of adverse reactions, alternative
      regimens are continuing to be evaluated. Of greatest promise to date for patients
      with mild-to-moderate disease are the alternative oral regimens of atovaquone,
      dapsone with trimethoprim, and clindamycin with primaquine. The addition of
      corticosteroids to anti-Pneumocystis therapy in patients with severe disease has
      been shown to improve both the short-term and long-term success of treatment. TMP
      SMX and aerosolized pentamidine have been shown to be effective in the primary
      and secondary prevention of pneumocystosis; prophylactic regimens currently under
      study include dapsone, dapsone with pyrimethamine, and once-monthly parenteral
      pentamidine.

PMID- 8278685
TI  - Ontogeny of the renin-angiotensin system.

PMID- 8278686
TI  - The macula densa mechanism for control of renin secretion.
AB  - Many questions remain concerning the precise mechanism by which the luminal
      signal for renin secretion is transmitted from the MD to the JG granular cell. It
      appears likely that a number of pathways may participate in MD-mediated changes
      in renin release, some of the agents serving to modulate release, others
      participating directly in signal transmission. Collectively, the current
      information suggests a transmission pathway that involves several steps. First,
      changes occurring in MD NaCl transport, which result directly from alterations in
      luminal NaCl concentration, act to initiate the response. Second, conveyance of
      this signal to the extraglomerular mesangial cells via a change in the ionic
      environment of the EGM field and/or a paracrine factor produced by the MD
      (perhaps NO) appear likely to be the next step. The subsequent steps probably
      include changes in prostaglandin production by the EGM, and possible
      participation of other paracrine factors produced by both endothelial and
      extraglomerular mesangial cells.

PMID- 8278687
TI  - Neural regulation of renin secretion.
AB  - In summary, there is now considerable evidence for an interaction between the
      renal sympathetic nerves and the baroreceptor and macula densa mechanisms in the
      control of renin secretion rate. Renal sympathetic nerve activity varies from
      minute to minute throughout the day. At times, increases in renal sympathetic
      nerve activity sufficient to cause a direct neural release of renin from
      juxtaglomerular cells may occur. Under other circumstances, changes in renal
      sympathetic nerve activity may be more modest, but still sufficient to modulate
      the renin secretion rate responses mediated by other mechanisms. The studies
      reviewed show that prevailing renal sympathetic nerve activity can modulate the
      magnitude of the renin secretion rate response to stimulation of the renal
      vascular baroreceptor and the tubular macula densa receptor mechanisms. The
      degree of interaction between the neural and non-neural mechanisms is dependent
      on the level of activation of the non-neural mechanisms and the intensity of
      renal sympathetic nerve activity.

PMID- 8278688
TI  - The renal proximal tubule renin-angiotensin system.
AB  - In conclusion, a complete RAS is present in the mammalian proximal tubule that is
      potentially autocrine and paracrine in nature. Maneuvers that stimulate renin in
      JG cells and renal vasculature appear to also stimulate renin in the proximal
      tubule. The subcellular localization of the different components and the
      regulation of this epithelial RAS still remain to be defined. This RAS may be
      important in regulation of proximal tubule NaCl and NaHCO3 transport. Finally,
      one can speculate that activation of this RAS may play a pathogenetic role in
      some patients with essential hypertension and in the hypertension and cyst growth
      seen in autosomal dominant polycystic kidney disease.

PMID- 8278689
TI  - The angiotensin (AT1) receptor.

PMID- 8278690
TI  - Dietary modification of the renin angiotensin system.

PMID- 8278691
TI  - Prorenin and the renin-angiotensin system in diabetic nephropathy.

PMID- 8278692
TI  - The renin gene and hypertension.

PMID- 8278693
TI  - The renin-angiotensin system in transgenic rats: characteristics and functional
      studies.

PMID- 8278694
TI  - [Biodemographical study in the Island of Pascua].
AB  - The aim of this study was to know the degree of miscegenation in the Easter
      Island population. One hundred two weddings carried out between 1987 and 1991
      were recorded and the proportion of marriages between islanders and immigrants
      was analyzed. Also, ABO and Rh blood groups of all deliveries occurred between
      1988 and 1991 were compiled. There was a particular tendency of islanders to
      marry with immigrants and the proportion of miscegenation was 75.5%. Additionally
      a decline in the frequency of A blood group is observed, comparing results from
      studies performed since 1932 up to date.

PMID- 8278695
TI  - [Prevalence of HTLV-I antibodies and possible risk factors in Chilean
      prostitutes].
AB  - Aiming to know the prevalence of HTLV-1 infection among high risk groups in
      Santiago, the antibodies against HTLV-1 were measured in 502 prostitutes coming
      from north and east Santiago. Antibodies were measured using ELISA and the
      positive samples were confirmed with an indirect immunofluorescence technique.
      Four subjects were positive, establishing a HTLV-1 infection prevalence of 0.8%.
      This number similar to that of other groups of prostitutes from South America and
      lower than that of prostitutes from Central America, region in which this
      infection is endemic. The measured prevalence was similar to that of other non
      promiscuous groups, suggesting that sexual transmission does not play an
      important role in our population.

PMID- 8278696
TI  - [Dyslipidemic patients with coronary cardiopathy. Effect of different doses of
      OMEGA-3 fatty acids on serum lipids and lipoproteins].
AB  - Twenty one male patients aged 35 to 70 years, with coronary artery disease and
      dislipidemia refractory to dietary treatment, were assigned to three parallel
      groups of 7 individuals each that received a supplemental dose of 2, 4 and 6
      g/day of omega-3 fatty acids during 60 days. After a 30 days wash-out period and
      60 of supplementation, subjects were weighed, a dietary survey was performed,
      serum levels of total cholesterol and triglycerides, the lipid content of serum
      lipoproteins and the content of EPA+DHA in plasma phospholipids were measured. A
      dose dependent increase in EPA+DHA content of phospholipids and no changes in
      weight or nutrient intake were observed during the supplementation period. With
      the 6 g dose, a significant reduction in total cholesterol, with a reduction in
      VLDL and increase in LDL cholesterol and a decline in VLDL triglycerides was
      observed. With the 4 g dose a reduction in total cholesterol at the expense of
      VLDL and HDL cholesterol and a reduction in VLDL triglycerides but no changes in
      total triglycerides was observed. No changes in serum lipids were observed with 2
      g dose. In patients with type IIA hyperlipidemia, a significant positive
      correlation was observed between DHA+EPA content of plasma phospholipids and LDL
      cholesterol, this correlation was not observed in patients with IIB or IV
      phenotypes. It is concluded that omega-3 fatty acids are ineffective as the only
      treatment for dislipidemias refractory to diet.

PMID- 8278697
TI  - [Protein and energy requirements in patients with severe head injury].
AB  - The aim of the present study was to assess the effect of severe head injury over
      resting energy expenditure and nitrogen losses. Eight patients with severe head
      trauma (mean Glasgow scale of 4.9 +/- 1.6), subjected to emergency craniotomy
      were studied; four patients had septic complications and none received steroids.
      Energy expenditure was measured using indirect calorimetry and nitrogen losses
      were assessed measuring 24 h urea nitrogen excretion on days 1, 4, 7 and 10 of
      the postoperative period. Twelve healthy males composed the control group.
      Measured energy expenditure in patients, evaluated in 22 occasions, was 35 +/-
      9.8 Kcal/kg/day or 145 +/- 41% of the estimation according to Harris-Benedict
      equations, compared to 22.0 +/- 4.6 Kcal/kg/day or 89.9 +/- 17.5% in the control
      group (p < 0.001). 24 h urinary urea nitrogen excretion in patients was 18 +/- 12
      g/day (range 5.2-46.9) and the catabolic index was 7.4 +/- 13.5. It is concluded
      that, due to the great individual variability in measured energy expenditure in
      these patients and their hypercatabolism, indirect calorimetry and nitrogen
      balance studies become useful tools to perform an adequate nutritional support.

PMID- 8278698
TI  - [Three years of acute bacterial meningitis in the pediatric service at the Temuco
      Regional Hospital].
AB  - The aim of this work was to study the clinical, epidemiological and laboratory
      features of 90 children, hospitalized between 1988 and 1991 with the diagnosis of
      acute bacterial meningitis in a region with a high proportion of aboriginal
      population. Twenty six percent of studied patients were of mapuche origin. The
      causative organism was identified in 82% of cases (H influenzae in 38% of cases,
      S pneumoniae in 29% and N meningitidis in 10%). H influenzae was resistant to
      ampicillin in 16% of cases and resistant to chloramphenicol in 4%. This agent was
      identified in 52% of patients of mapuche origin compared with 33% of non mapuche
      patients. Seventy three percent of children were less than 2 years old. Thirty
      seven percent of children had complications during hospitalization, 12 children
      died (13.3%) and 38% of children had neurological sequelae at the moment of
      discharge.

PMID- 8278699
TI  - [Effect of the prolonged use of intrauterine devices and oral contraceptive on
      iron nutrition].
AB  - The aim of this work was to study the effect of prolonged use of intrauterine
      devices (IUD) and oral contraceptives (OCO) normally prescribed at outpatient
      clinics of the Health Service on iron nutrition. Two hundred twenty three healthy
      women, aged 20 to 39 years were studied. Of these, 100 were using IUD and 97 OCO
      for three to five years and 26 were not using any pharmacological or mechanical
      contraceptive method (control group). Serum ferritin was significantly higher in
      the OCO group compared to IUD and control groups (58.9 +/- 2.2; 26.2 +/- 2.1 and
      21.1 +/- 2.4 ng/ml respectively). There was a positive correlation between serum
      ferritin and hemoglobin in IUD and control groups and between ferritin and
      transferrin saturation in the OCO and control groups. The frequency of storage
      iron depletion (defined as a serum ferritin < 12 ng/ml) was 6.3, 0 and 25% in the
      IUD, OCO and control groups respectively. The numbers for iron-deficient
      erythropoiesis (defined as a transferrin saturation < 15%) were 7, 3 and 4% and
      for iron deficiency anemia, 6.5, 0 and 8%. It is concluded that the chronic use
      of IUDs leads to iron depletion and that measures to improve iron nutrition among
      women using them should be adopted.

PMID- 8278700
TI  - [Characteristics of acute myocardial infarction in patients with diabetes
      mellitus].
AB  - We analyzed retrospectively the clinical course and prognosis of 565 consecutive
      patients with acute myocardial infarction (AMI), 117 of them with a previous
      history of diabetes mellitus. Male/female ration was 7.9/2.1 in non diabetics and
      7.0/3.0 in diabetics (p < 0.03). Incidence of hypertension and hyperlipidemia was
      higher in diabetic patients as well as history of congestive heart failure (13.7%
      vs 6.5 in non diabetics p < 0.01). The type and location of AMI did not differ
      among groups, however the incidence of congestive heart failure Killip class III
      IV was higher in diabetic patients (31.6 vs 21.2%). Peak CPK values were lower in
      diabetics (1.270 +/- 1.179 vs 1.648 +/- 1.377 U/l p < 0.01). Cardiac mortality
      was higher one month and one year after AMI in diabetics (17.1 vs 13.6% and 21.4
      vs 17.8% respectively, p < 0.01). Univeriate and multivariate analysis identified
      new bundle branch block, heart failure and advanced age as independent predictors
      of mortality in both groups of patients. It is concluded that the worst prognosis
      of diabetic patients with AMI may be related to a previously depressed
      ventricular function and that appropriate metabolic control and treatment of
      associated risk factors, could improve the prognosis of diabetics patients with
      AMI.

PMID- 8278701
TI  - [Thyroid profile in normal pregnancy].
AB  - The aim of this study was to update the thyroid hormone profile in normal
      pregnant women with adequate iodine nutrition, to analyze the physiological
      changes that occur during pregnancy and to know the role that TBG and bHCG exert
      on these changes. One hundred six pregnant women without goiter, former thyroid
      diseases or positive antimicrosomal antibodies were studied. Fifty three of them
      were prospectively followed during the gestational period. Thirty age matched non
      pregnant women were studied as a control group. Serum T3t, T4t, T41, conventional
      and IRMA TSH, rT3, TBG, bHCG, antimicrosomal antibodies and urinary iodine
      content were measured. Median urinary iodine content was 18.9 ug/ml in pregnant
      women, discarding iodine deficiency, the main observed changes occurred between
      weeks 6 and 14 with significant elevations of T3t, T4t, T41, rT3, TBG and bHCG
      and TSH decrease. There was a positive correlation between TBG and T3t and T4t
      indicating a causal relationship. There was a negative correlation between T41
      and TSH and between TSH and bHCG and a positive correlation between T41 and bHCG,
      suggesting a thyroid stimulator effect of bHCG which would raise T41 and thus
      inhibit TSH secretion.

PMID- 8278702
TI  - [Treatment of hyperthyroidism during pregnancy: experience with 19 cases].
AB  - Untreated hyperthyroidism in pregnant women is associated with a high incidence
      of maternal and fetal complications. Thus, its treatment is mandatory, ideally
      using PTU because it has lesser transplacental passage. From 1987 and 1991 we
      have attended 19 hyperthyroid pregnant women. Of these, 18 had diffuse and 1
      nodular goiter and in 10, thyrotoxicosis preceded pregnancy. PTU was used in 17
      women (7 received it along the whole pregnancy), five had to be operated due to
      poor response, one received propranolol and one patient was not treated due to
      lack of attendance. Cesarean section was performed in 12 women, 5 had vaginal
      delivery, one had a miscarriage at the 20th week of pregnancy due to a
      neurological malformation and one patient was lost from control before delivery.
      The newborn of the untreated woman had a neonatal thyrotoxicosis and the resting
      16 did not show evidence of thyroid disfunction. Newborns from mothers receiving
      PTU until delivery had significantly lower rT3 levels and non significant changes
      in T4 and T3. At the end of the observation period, 8 patients were euthyroid, 3
      hypothyroid (2 after 131-l and 1 after surgery), 4 continued on PTU and 4 were
      lost from control. It is concluded that the outcome of pregnancy may be
      uneventful in hyperthyroid women provided that there is a close and adequate
      follow up.

PMID- 8278703
TI  - [Evaluation of the determination of total cholesterol in Chilean clinical
      laboratories].
AB  - The precise and accurate measurement of total cholesterol is necessary to
      correctly identify hypercholesterolemia. The aim of this study was to assess the
      measurement of serum cholesterol in clinical laboratories using as acceptability
      criteria the recommendations of the "National Cholesterol Education Program"
      (that consider acceptable a deviation < 5% from the real value and ideal a
      deviation < or = 3%). In each of three assessments, three pools of lyophilized
      sera with different levels of cholesterol were used method. Twenty nine to 42.3%
      of laboratories had results within the ideal interval and 49.5 to 60% within the
      acceptable range of deviation. In the last assessment, only 17% of laboratories
      had their three values within the ideal range. Only 39.4% of laboratories use 200
      mg/dl as the cut off point to diagnose hypercholesterolemia. It is concluded that
      the standardization of cholesterol measurement and the use of a common cut off
      point to diagnose hypercholesterolemia must be emphasized.

PMID- 8278704
TI  - [Leiomyosarcoma of the saphenous vein].
AB  - A 48 years old male presenting with a painless tumor of the right thigh is
      reported. An initial surgical excision showed that the tumor was joint to the
      saphenous vein. The histopathological study showed that it was a venous vascular
      leiomyosarcoma of intermediate degree of malignancy. The patients was re-operated
      performing a resection of the abductor muscle and two weeks later was subjected
      to radiotherapy (50 Gray). The only postoperative sequel was a moderate
      lymphedema of the right limb. This is the first reported case in the Chilean
      literature.

PMID- 8278705
TI  - [Thyroid gland and pregnancy].

PMID- 8278706
TI  - [Medical and legal aspects of medical liability lawsuits].
AB  - The principal legal resolutions about medical liability lawsuits in Chile are
      analyzed. The causes for the accusations and for the increase in the number of
      suits in Chile, according to research performed by the authors, are described. An
      improvement in patient-physician relationships, a better alliance among
      physicians, a correct certification of medical specialties, the demand of
      adequate technological and humans resources to perform medical functions
      optimally, the supervision of medical work and the legal support and advice of
      medical societies are recommended strategies to prevent these lawsuits.

PMID- 8278707
TI  - [Auricular fibrillation, systemic embolism and anticoagulant treatment].
AB  - The risk of arterial embolism, specially cerebral, in patients with mitral
      stenosis associated atrial fibrillation is seventeen fold greater than that of
      the general population and five fold greater than that of non rheumatic atrial
      fibrillation. The usefulness of oral anticoagulant therapy in patients with
      atrial fibrillation and mitral stenosis is clear. In patients with non rheumatic
      atrial fibrillation, the controversy about its usefulness has been cleared with
      five recent reports showing a significant benefit or oral anticoagulation. We
      believe that these results may be applied to the routine management of these
      patients provided an adequate patient selection, consideration of
      contraindications and the use of a low anticoagulation range. Aspirin
      effectiveness in these patients is unsettled. One study showed benefits of 375
      mg/day in patients younger than 75 years. The embolic risk in patients with
      atrial fibrillation must be stratified. High risk patients require the use of
      oral anticoagulation with an INR range between 3 and 4.5; those with medium risk
      require an INR between 2 and 3 and in some, aspirin use may be an alternative.
      When electrical cardioversion is indicated, oral anticoagulation must be used
      when atrial fibrillation has lasted for more than two days. In these cases, it is
      advisable to postpone cardioversion for three weeks after oral coagulation has
      started and to maintain this treatment for 3 or 4 additional weeks after
      cardioversion.

PMID- 8278708
TI  - [Psychosocial sexual phenotypes. A proposition and their ontogeny].
AB  - A proposition of operational phenotypes and ontogeny for psychic and social sex
      is presented. These phenotypes are defined according to the three major theories
      of Biology: cell, inheritance and evolution. Sexuality is defined, for species,
      as the ability to produce individuals in creative genetical process by means of
      genetical recombination associated with reproduction. Sex is defined, for
      individuals, as the set of characters (phenotypes) that allow those gene
      recombinative and reproductive processes. The Psychic Sex includes: the Sexual
      configuration of identity, the Sexual appetizing configuration, the Genital
      connection, the Somatoerogenic connection, the Integration of psychic sex into
      personality and the Sexual psychomotor form. The Social sex includes those
      individual behaviors performed isolately or collectively that realize sexual
      processes in the species. The ontogeny of these phenotypes considers that they
      are the product of the interaction between the genotypes and environments. The
      endogenous neuroendocrine differentiation, mainly due to genetic factors.,
      interacts with the familial and social environment, which presents a set of
      sexual polar semiotic factors. The endogenous differentiation makes more or less
      probable to acquire further sexual differentiations yielded by co-living
      (interactions that are brought about by living together) with that differentiator
      (that produces differentiation) polar environment.

PMID- 8278709
TI  - [Message from editors to authors: review articles. How can the scientific and
      educational results be improved?].
AB  - Most biomedical journals include review articles that pretend to provide the
      readers with an updated, synthetic and critical appraisal of some important
      topic. These articles are usually written by experts in the topics reviewed.
      There are no conventional or universally accepted requisites for the formal
      organization of contents in a review article. This is in contrast with other
      kinds of original articles. Therefore, to guide the authors on how to improve the
      review articles to be submitted to Revista Medica de Chile, some recommendations
      are proposed. These recommendations were based in the editors' experience and in
      other pertinent publications: 1) The scope and purpose of the review article
      should be established in the introductory paragraphs; 2) The methodology used in
      the selection of the literature reviewed and the time span covered by the search,
      should also be specified; 3) The author of the review article should
      systematically appraise the validity of the methods employed in the papers
      reviewed. A similar attitude should be observed with regards to the results,
      discussions and conclusions. The limitations and inconsistencies found should be
      pointed out; 4) The author of the review article should state his (her) own
      conclusions, identifying the solid as well as the weakly established facts; 5)
      Whenever feasible, a proposal of future lines of research envisioned after
      reviewing the literature, is commendable; 6) The literary style of the article
      should be kept as interesting as possible, to motivate the prospective readers;
      7) The scope of the specific journal where the author intends to submit the
      review article, should always be kept in mind.

PMID- 8278710
TI  - [Heparin in pregnant women undergoing hemodialysis. Doses according to heparin
      kinetic models].

PMID- 8278711
TI  - [Prevalence of mental disorders at emergency service].
AB  - Aiming to know the frequency of mental disorders among patients consulting a
      general hospital emergency ward, 2834 medical records of such patients were
      retrospectively reviewed. 8.4% of consultations were due to mental disorders.
      Sixty four percent of patients consulting for mental disorders were women.
      Anxiety disorders comprised 57.6% of consultations due to mental disorders and
      intoxications 7.6%. Eighty percent of the latter were consequence of suicidal
      attempts, being the most common method the use of benzodiazepines. A low percent
      of these patients were referred to psychiatry. The low frequency of psychiatric
      referrals and the importance of psychiatric advice in emergency rooms is
      discussed.

PMID- 8278712
TI  - [Digestive system cancers and pregnancy].
AB  - Digestive tract cancers are infrequent during pregnancy. Prognosis is usually
      dismal both because diagnosis is delayed as a result of symptoms being ascribed
      to the pregnancy and because saving both the mother and fetus is difficult. A
      review of the relevant literature, focused on colorectal and gastric cancers
      which are the most common forms, emphasizes the need for early diagnosis and for
      adjusting treatment to gestational age at diagnosis.

PMID- 8278713
TI  - [Gynecologic cancers and pregnancy. With the exception of breast cancer].
AB  - Pregnancy should be a privileged opportunity to detect the two gynecologic
      cancers which occur most frequently during this period (breast cancer excepted).
      Their detection during pregnancy doesn't influence the maternal prognosis on
      condition that an ideal therapeutic protocol is applied. The embryonic and fetal
      toxicity of anticancerous treatments is known to justify medical pregnancy
      interruption in some cases, and in others allow their utilization looking forward
      to fetal viability.

PMID- 8278714
TI  - [Breast cancer and pregnancy].
AB  - Breast cancer is generally believed to carry a worse prognosis during pregnancy
      because of the potential adverse effects of anticancer treatments on the fetus
      and of pregnancy related hormonal and immunological modifications on the disease.
      Problems arise both with breast cancers diagnosed during or immediately after
      pregnancy and with pregnancies occurring in patients previously treated for
      breast cancer. The incidence of these problems is difficult to estimate, in part
      because pregnancy-related changes in the breasts obscure clinical and
      radiological manifestations. Prognosis depends more on patient age than on
      gestational age at diagnosis. Other prognostic factors include size of the tumor
      and node involvement. Although the outcome of N+ tumors is more severe during
      pregnancy, overall the poor prognosis of breast cancer during pregnancy is due to
      the young age of patients and pregnancy has no bearing on prognosis after
      adjustment for stage. Similarly, women who become pregnant after being treated
      for breast cancer do not have worse outcomes. Management is difficult because
      some treatments cannot be used during pregnancy; the approach is similar to that
      used in non-pregnant women, although chemotherapy should be given only after 14
      or 15 weeks gestational age and irradiation therapy only after delivery.

PMID- 8278715
TI  - [Pregnancy without medical monitoring: obstetrical and neonatal prognosis. A
      retrospective study of 88 cases].
AB  - Unregistered and unmonitored pregnancies account for 0.2 to 0.6 p. cent of all
      pregnancies. They essentially concern young, single, primiparous mothers from
      disadvantaged social backgrounds. Labour and delivery are generally without
      difficulty but the neonatal prognosis is impaired by a high proportion of
      premature and underdeveloped infants, often requiring a long stay in a pediatric
      unit.

PMID- 8278716
TI  - [Pathologic Doppler flowmetry of the uterine artery and histologic changes of the
      placenta].
AB  - The usefulness of velocimetric study of the uterine arteries during high-risk
      pregnancies and in particular in the presence of presumed or confirmed maternal
      pathology is now recognized. Is it possible to identify a link between
      hemodynamic disturbances affecting the uterine arteries and histological
      abnormalities of the placenta? This was the aim of the present study.
      Histological examination of the placenta was routinely requested after delivery
      when uterine artery Doppler had been pathological during pregnancy (index and/or
      notch). Fifty five placentas were studied, all but one being pathological. This
      essentially involved ischemic lesions (including retroplacental hematomas), for
      which Doppler investigation appears to be a good indicator. Forty placentas were
      hypotrophic and 2 hypertrophic. Thus uterine artery Doppler during pregnancy
      appears to accurately reflect the histological state of the placenta and possibly
      even its functional value.

PMID- 8278717
TI  - [Adenomyosis and pathological delivery. Apropos of a case].
AB  - The author uses a case to review the link between adenomyosis and pathological
      delivery. Such a link has been suspected in the past, and was confirmed in the
      present case by hysteroscopy after spontaneous abortion. Coagulation-diathermy of
      adenomyosis via hysteroscopy enabled a subsequent pregnancy culminating in normal
      delivery.

PMID- 8278718
TI  - [Induction of labor in fetal death in utero using a Foley catheter and extra
      amniotic perfusion of physiologic serum].
AB  - Nineteen cases of induction of labour by Foley catheter and extra-amniotic
      perfusion of normal saline for fetal death in utero occurring more than 24 weeks
      after the LMP were collected in the La Rabta Maternity and Neonatology Centre,
      Tunis, during the final 6 months of 1987. The mean age of the women was 27.8 and
      their mean parity 2.9. Two patients had uterine scars. The mean duration of the
      pregnancy was 33.3 weeks and initial Bishop score was 4 or less. When the
      catheter fell out, after 26.4 hours on average, the Bishop score had improved by
      4.5 points. Labour occurred spontaneously in 5 cases and required oxytocin
      stimulation in 5 cases. The interval between induction and fetal expulsion was
      44.4 hours. Delivery was followed by routine manual evacuation of the uterus. Two
      complications were seen: one case of accidental rupture of the membranes and one
      of rupture of the uterus affecting a scarred uterus. The authors point out
      certain risk factors concerning rupture of the uterus which should be considered
      to be contraindications to the method. With the exception of these situations,
      this method of induction is recommended because of its advantages of efficacy,
      safety and low cost, in particular in developing countries.

PMID- 8278719
TI  - [A technic for the prevention of terminal (juxta-vesical) ureteral lesions during
      radical lymphadeno-colpo-hysterectomy for uterine cancer].
AB  - In certain cases (i.e. selectively and not routinely) of radical lymphadeno-colpo
      hysterectomy for uterine carcinoma, the authors section the uterosacral ligaments
      at the outset, which enables the uterus to be brought up and thus facilitates
      dissection, ligation and section of the supra-uterine vesico-uterine pedicles,
      avoiding damage to the terminal (juxta-vesical) ureter.

PMID- 8278720
TI  - [The sources of medical ethics: Hippocrates and his disciples].

PMID- 8278721
TI  - [Ethics: a reflection or a practice?].

PMID- 8278722
TI  - [Why teach ethics?].

PMID- 8278723
TI  - [Back to the origins of our days, a new science: genetics].

PMID- 8278724
TI  - [The "new genetics" and the role of nurses].

PMID- 8278725
TI  - [Prenatal diagnosis: experience of one nurse].

PMID- 8278726
TI  - [Bioethics and predictive medicine].

PMID- 8278727
TI  - [Role of the family in the therapeutic decision to stop life support].

PMID- 8278728
TI  - [Anticipatory management of handicapped patients].

PMID- 8278729
TI  - [The therapeutic decision to stop neonatal life support. The role of the family
      and the nursing care team].

PMID- 8278730
TI  - [Ethics and solidarity].

PMID- 8278731
TI  - [For "good clinical practice": the Huriet law].

PMID- 8278732
TI  - [Tears. 1st Part: Their mechanisms].

PMID- 8278733
TI  - [Nursing guides, the 1993 batch].

PMID- 8278734
TI  - [If we dare to speak of death, then we will not die].

PMID- 8278735
TI  - [One does not cut off one's ear for nothing].

PMID- 8278736
TI  - [Professional practice. "The decree of competence". Official journal of March 16,
      1993].

PMID- 8278737
TI  - [Legionellosis associated with pneumopathies in Sao Paulo. Study of the etiologic
      confirmation by isolation and serology].
AB  - The role of Legionella sp as an important pathogen, although reported in many
      countries, had not been well documented in Brazil. The main objective of the
      present study is to detect this organism or it's immunological response in
      patients with pulmonary infections in the city of Sao Paulo. For this purpose,
      specific laboratory methodology was introduced to cultivate the agent and
      demonstrate specific antibodies by serology. Patients from two University centers
      in Sao Paulo were studied: 100 from the Hospital Universitario, University of Sao
      Paulo with general pulmonary infections and 100 from Hospital das Clinicas,
      Faculdade de Medicina, University of Sao Paulo. The latter were selected to
      exclude pulmonary infections of other bacterial aetiology, and 30 of these were
      selected from the Renal Transplant Unit. Clinical specimens for cultures included
      sputum tracheal secretion, pleural, fluid, bronchial washing or lung tissue
      biopsy. Isolation of Legionella sp was attempted in BCYE medium with and without
      antibiotics, presumptive diagnosis by biochemical methods and identification
      through direct immunofluorescence staining and slide agglutination test. Direct
      evidence of the organism in tissue was attempted by direct immunofluorescence
      staining. Specific antibodies for Legionella pneumophila serogroup 1 were tested
      by the indirect immunofluorescence assay. Serology was also carried out in
      specimens from human contacts with Legionnaires' Disease. Legionella pneumophila
      serogroup 1 was isolated from two patients, demonstrating the presence of the
      pathogen in this country. Serology was able to establish present or past
      infection with the agent in 16 of the 100 patients from Hospital das Clinicas and
      in only one from Hospital Universitario. In patients considered as high risk
      groups from Hospital das Clinicas with renal transplantation, serology for
      present or past Legionellosis was positive in 33% and in 8.5% for community
      acquired infections. Serology in specimens from Medical personnel in contact with
      patients of Legionnaires' disease was positive for past infection in one single
      subject, confirming information already published that direct transmission from
      person to person is unusual. The introduction of specific methods for
      laboratorial evidence of Legionella sp infections at the Hospital das Clinicas
      Faculdade de Medicina USP community has permitted diagnosis in able time to allow
      use of specific anti-microbial therapy, with good results.

PMID- 8278738
TI  - Five cases of nosocomial and community-acquired Legionnaires' disease in Sao
      Paulo, Brazil.
AB  - Legionella sp has been emerging over the last decade as an important cause of
      pneumonia both hospital and community-acquired. Following an outbreak in a Renal
      Transplant Unit stocked serum was tested for antibodies against Legionella
      pneumophila serogroup 1, and 5 cases of Legionnaires' Disease were reviewed. Two
      of the cases were nosocomial and three cases were community-acquired. Clinical
      and laboratorial aspects were similar to those expected for other causes of
      pneumonia, however jaundice was encountered in two cases. This study suggests
      that the real incidence of pneumonia caused by Legionella sp is being
      underestimated and the authors emphasize the importance of considering
      Legionnaires' Disease when empirically treating community-acquired pneumonia.

PMID- 8278739
TI  - Antimicrobial resistance and plasmid detection in strains of the Bacteroides
      fragilis group.
AB  - Resistant populations of the Bacteroides fragilis group bacteria (two reference
      ones and two isolated from human and Callithrix penicillata marmoset) were
      obtained by the gradient plate technique, to clindamycin, penicillin G,
      metronidazole and mercuric chloride. All the four tested strains were originally
      susceptible to the four antimicrobial drugs at the breakpoint used in this study.
      MICs determination for the four cultures gave constant values for each
      antimicrobial, on the several steps by the gradient plate technique. The
      intestinal human B. fragilis strains showed three DNA bands, that could be
      representative of only two plasmids in the closed covalently circular (CCC) form
      with molecular weights of approximately 25 and 2.5 Md. The results do not permit
      an association between the presence of plasmid in the human strain with the
      susceptibility to the studied drugs. The four strains were beta-lactamase
      negative in the two methods used, and no particular chromosomal genetic
      resistance marker was demonstrated. The resistance (MIC) observed, after contact
      with penicillin G and mercuric chloride, were two-fold in the four tested
      strains.

PMID- 8278740
TI  - Transmission of Schistosoma mansoni under experimental conditions using the
      bovine--Biomphalaria glabrata-bovine model.
AB  - Three calves experimentally infected with Schistosoma mansoni, and passing viable
      eggs in feces, as well as 5 normal calves (coming from a non-endemic area for
      schistosomiasis) kept as controls, were maintained in an enclosure (850 m2 in
      area). In this enclosure, a tank with water received 500 laboratory reared
      Biomphalaria glabrata. All the control calves were infected for a period ranging
      from 79 to 202 days after the beginning of the experiment, and afterwards
      presented viable S. mansoni eggs in feces. The mean worm recovery was 555. The
      snail population increased throughout the experimental period, showing a high
      number of B. glabrata infected with S. mansoni (42% on average). According to the
      present study, bovine has been suggested as having potentially a role in the
      maintenance of the life cycle of S. mansoni.

PMID- 8278741
TI  - Host cell adhesion to Schistosoma mansoni larvae in the peritoneal cavity of
      naive mice. Histological and scanning electron microscopic studies.
AB  - Cercariae of Schistosoma mansoni inoculated into the peritoneal cavity of naive
      mice induced host cell adhesion to their surface, but after 90 minutes the number
      of adherent cells sharply decreased. The cell detachment is progressive and
      simultaneous to the cercaria-schistosomule transformation. The histological study
      showed mainly neutrophils in close contact with the larvae. Mononuclear cells and
      some eosinophils were occasionally seen surrounding the adherent neutrophils. The
      scanning electron microscopy showed cells displaying twisted microvilli and
      several microplicae contacting or spreading over the larval surface, and larvae
      completely surrounded by clusters of cells. These results suggest that the
      neutrophils recognize molecules on the cercarial surface which induce their
      spreading.

PMID- 8278742
TI  - [Evaluation in mice of the efficacy of antivenins administered at the site of the
      intramuscular inoculation of the Crotalus durissus terrificus venom].
AB  - The efficacy of the Crotalus durissus terrificus antivenom administration by
      intramuscular (im) injection at the same place of the im inoculation, of the C.
      d. terrificus venom was evaluated in mice. In three experiments two DL50 of the
      venom were inoculated and the antivenom was administered in three different ways:
      half of the ED50 by intraperitoneal (ip) administration and half by injection, at
      the same place, immediately after the venom inoculation and thirty minutes after
      the im venom inoculation; four fifth of ED50 by ip administration and one fifth
      by injection, at the same place and thirty minutes after the venom inoculation.
      The antivenom that was administered by intraperitoneal route provided a higher
      protection to mice (a lower death rate in a 48 hours period) than when it was
      administered in parts, by intramuscular injection, at the same place of the venom
      inoculation (p < 0.05). Therefore, it is concluded that this should not be used
      in human beings bitten by snakes.

PMID- 8278743
TI  - Interaction between neutrophils and Schistosoma mansoni larvae in vivo. A
      transmission electron-microscopic study.
AB  - Schistosoma mansoni cercariae were inoculated into the peritoneal cavity of naive
      mice and recovered 30 minutes later. Ultrastructural studies showed that
      neutrophils adhere to the larval surface and participate in the removal of
      glycocalyx by phagocytosis. This finding suggests that the neutrophils can play a
      role on the cercaria-schistosomulum transformation process.

PMID- 8278744
TI  - [Congenital Chagas disease in the city of Salta, Argentina].
AB  - The immune response to Trypanosoma cruzi was studied in our hospital in 937
      pregnant women(PW) and their 929 newborns(NB), group I; 4 NB from this center not
      included in the first group, group II and 35 NB derived from other centers, group
      III. Two positive results among indirect hemagglutination (IHA), complement
      fixation(CF) and indirect hemagglutination(IHA), complement fixation(CF) and
      indirect immunofluorescence(IIF) tests were considered as the criterion of
      previous infection with T. cruzi in PW. The presence of T. cruzi in blood,
      explored in fresh smears by serial micro-hematocrite and/or by xenodiagnosis, was
      the only criterion to define infection in NB. All NB were followed up by direct
      agglutination (DA) with or without 2 mercaptoethanol (DA-w2ME, DA-wo2ME) and IIF
      in order to establish the specific antibody kinetics. Clinical studies on NB with
      T. cruzi infection include routine laboratory tests. Benznidazole (3 to 7
      mg/kg/day) and, in 1 case, nifurtimox (15 mg/kg/day) were employed as therapeutic
      agents. T. cruzi infection was confirmed in 149 PW(15.9%), table I. These
      chagasic mothers delivered 6 chagasic NB (CCHD-NB), (4%). Diagnosis of congenital
      Chagas' disease accounted for a total of 12 NB out of the 968 studied. 4 out of
      them were positive by both microhematocrite and blood smears and 7 by
      microhematocrite alone. Xenodiagnosis was performed in 2 NB resulting positive in
      both cases, table II. The most usual clinical findings included hepatomegaly
      (present in all cases), splenomegaly 8/12, jaundice 10/12 and prematurity 5/12,
      table 3. Laboratory findings showed anemia to be of hypochromic microcytic type
      in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278745
TI  - [Triatoma delpontei Romana & Abalos, 1947 (Hemiptera, Tratominae) in the
      Brazilian State of Rio Grande do Sul].
AB  - Triatoma delpontei (Romana & Abalos, 1947) (Hemiptera, Triatominae) is an
      ornithophilic sylvatic with a particular association to the psittacid Myiopsitta
      monachus (Boaddert, 1783). It is found in the continental biogeographical
      province of the Chaco, where it inhabits the nests or M. monachus, in subtropical
      xerophytic forests. The authors report the first finding of T. delpontei in
      Brasil, in the "campanha" region of the State or Rio Grande do Sul (Barra do
      Quarai, Uruguaiana), on the right bank of the River Cuareim, not far from de
      Uruguayan border.

PMID- 8278746
TI  - [Cryptococcus neoformans var. neoformans isolated from soil].
AB  - We inquiry, in the epidemiologic history of 42 patients with cryptococcosis, the
      contact with pigeon, trying to find the possible source of infection. Of these
      patients, the information compatible with ecologic niche of Cryptococcus
      neoformans was positive in 16. Fifty nine samples were recovered from soil,
      associated with pigeon habitat. We found C. neoformans in four occasions, one in
      the capital and three in the interior of state. C. neoformans, serotype A,
      recovered from a central spine fluid coincides with the serotype of the fungus
      recovered downtown Porto Alegre, in a place suggested by the patient as possible
      source of infection, characterizing of a case of Cryptococcus neoformans. var.
      neoformans.

PMID- 8278747
TI  - [Treatment with fluconazole of severe fungal infections in immunocompromised
      patients].
AB  - Fluconazole therapy was evaluated prospectively in 108 patients with
      immunosupression and serious fungal infections. Patients were enrolled if they
      had a life-threatening fungal infection and conventional therapy had failed to
      eradicate infection, had caused serious toxic reactions, or was contraindicated.
      Patients were treated with 50 to over 400 mg/day initially. AIDS was underlying
      risk factor in 66.6% of the patients evaluated in the study and in 92.9% of 57
      patients with cryptococcal infection. Satisfactory clinical response was observed
      in 43 patients with active cryptococcal infection and in 39 patients with active
      candidiasis, 90.7% and 92.3% respectively. Concerning mycologic response, 63.3%
      and 80.7% of 30 patients with cryptococcal infection and 26 patients with
      candidiasis respectively had final negative cultures. Eleven patients (10.2%) had
      adverse effects possibly due to fluconazole therapy. Fluconazole may be effective
      in the treatment of cryptococcal infection and candidiasis and can be an
      alternative to conventional antifungal therapy.

PMID- 8278748
TI  - Immunization against hepatitis B in children from endemic zone: evaluation of the
      antibody response against the DNA recombinant vaccine (Engerix B-20 MCG).
AB  - A previous seroepidemiological study in the rural zone of Vargem Alta (ES)
      SouthEast of Brazil, showed a prevalence of up to 9% of hepatitis B surface
      antigen (HBsAg) in some areas. One hundred susceptible children aging 1 to 5
      years old were selected and immunized with a recombinant DNA hepatitis B vaccine
      (Smith-Kline 20 mcg) using the 0-1-6 months vaccination schedule. Blood samples
      were collected at the time of the first vaccine dose (month 0) in order to
      confirm susceptible individuals and 1,3,6 and 8 months after the first dose, to
      evaluate the antibody response. Our results showed that two and five months after
      the second dose, 79% and 88% of children seroconverted respectively, reaching 97%
      after the third dose. The levels of anti-HBs were calculated in milli
      International Units/ml (mIU/ml) and demonstrated the markedly increase of
      protective levels of antibodies after the third dose. These data showed a good
      immunogenicity of the DNA recombinant hepatitis B vaccine when administered in
      children of endemic areas.

PMID- 8278749
TI  - [Pulmonary involvement in malaria (review)].
AB  - Pulmonary involvement occurs in 3 to 10% of the cases of Plasmodium falciparum
      malaria and represents the most serious complication of this infection, with a
      lethality of about 70%. The understanding of its pathogenesis is still very
      fragmentary, however it is recognized that activation of the immune system by
      antigens released by the parasite plays an important role in the induction and
      worsening of lung damage. Capillary endothelial cells, which control the flux of
      fluids to the interstitial space, appear to be the most involved structure. These
      cells are activated by cytokines, produced by lymphocytes and macrophages during
      the immune response, and express receptors and molecules of adhesion, allowing
      for sequestration of parasitized erythrocytes and adherence of cells, which will
      produce locally inflammatory mediators. The inflammatory reaction and lesion of
      endothelial cells that ensue, together with the hemodynamic alterations induced
      by the capillary blockade due to the sequestration of parasitized erythrocytes
      and leukocytes, cause alterations of the vascular permeability and transfer of
      liquid to intertitial space and alveoles. Severe cases are clinically expressed
      by a picture of Adult Respiratory Distress Syndrome. The clinical manifestations
      of pulmonary involvement may start suddenly at any time during the course of
      malaria, even after disappearance of circulating parasites. The inducing factors
      are unknown. Hyperparasitemia, renal failure and pregnancy are predisposing
      factors. The prognosis will depend on how fast the diagnosis is established and
      convenient treatment initiated. If parasites are present they shall be treated
      with schizonticidal drugs, hemodynamic parameters continuously evaluated,
      preferably through a Swam-Ganz catheter. Appropriate oxygen supply and fluid
      balance have to be warranted. Other complications of malaria, frequently
      associated to the pulmonary involvement, need special attention and proper
      treatment. A better understanding of the pathogenesis of lung damage associated
      to malaria will certainly help to improve treatment and reduce morbidity and
      mortality.

PMID- 8278750
TI  - [Clinico-mycological study of onychomycosis in elderly patients].
AB  - Physical examination of nails was carried out in 210 elderly patients and nail
      scrapings were obtained from onychomycosis suggested lesions in order to
      determine their causative agents, incidence and clinical characteristics.
      Diagnostic was confirmed by the isolation of the agents from 74 patients, mainly
      from toe-nails (incidence 35.2). Tinea pedis occurred in 25% of the cases and
      Diabetes mellitus was the most prevalent associated disease and the most frequent
      clinical characteristics were the thickening, the opacity and the presence of
      longitudinal strias in the surface of the nails. It was compared the results
      obtained by microscopic examination and by culture. Trichophyton rubrum was the
      most common dermatophyte isolated; Candida parapsilosis was dominant among
      Candida species.

PMID- 8278751
TI  - [Alcoholism and syphilis: prevalence and clinical and hepatic biochemical
      changes].
AB  - The prevalence of syphilis in chronic alcoholics and the hepatic clinical and
      biochemical alterations were evaluated in patients with both entities. The
      prevalence of syphilis in patients with other psychiatric diagnosis was taken as
      control. The patients were asymptomatic or oligosymptomatic with respect to
      hepatic alcoholic dysfunction or to any manifestation of the three clinical
      stages of syphilis. Alcoholics (206 patients) and patients with other psychiatric
      conditions (228 patients) were submitted to clinical examination and to
      quantitative serology for syphilis (Wasserman and VDRL), yielding 6.3% and 3.1%
      of seropositivity, respectively. No statistically significant difference was
      observed between alcoholics of the seropositive or seronegative groups, as to the
      frequencies of clinical or biochemical alterations which would indicate hepatic
      alterations.

PMID- 8278752
TI  - [Paracoccidioides brasiliensis, a new sample isolated from feces of a penguin
      (Pygoscelis adeliae)].
AB  - The Authors show the results obtained through the study of a Paracoccidioides
      strain isolated from a penguin in the Uruguaian Antartide by GEZUELE et al.
      (1989). From the fecal mater it was isolated a fungus which was recently
      considered as a new species of the genus Paracoccidioides--P. antarcticus.
      However, the mycological and immunochemical studies including the demonstration
      of the 43 kDa glycoprotein by immunodiffusion test, SDS-PAGE and
      immunoelectrophoresis disclosed that such strain is similar to P. brasiliensis.
      Other studies, based on molecular taxonomy, including karyotyping, are the only
      tools to confirm the possibility of such strain to be a variant of P.
      brasiliensis. The Authors report the epidemiological significance of that finding
      and suggest a review in the knowledge of the ecological "niche" of P.
      brasiliensis.

PMID- 8278753
TI  - The ecology of Triatoma sordida in natural environments in two different regions
      of the state of Minas Gerais, Brazil.
AB  - A study was undertaken about T. sordida in the natural environment in two
      different regions of the state of Minas Gerais: Itapagipe (Triangulo), an area of
      cerrado modified by the formation of fields of pasture and agriculture, and Mato
      Verde (north) an area of transition between caatinga and cerrado with profound
      deforestation in the last years due to the expansion of cotton cultivation. In
      both regions the principal ecotopes identified were hollow trees and the bark of
      live or dead trees, where the occurrence of a food source is not frequent. In
      this environment, the triatomines utilize various food sources; opposums appear
      to represent an important source of infection. In the north of Minas, a greater
      concentration of reservoirs and vectors was observed than in the Triangulo which
      could explain the higher level of infection of the triatomines in the north.
      Close attention to the process of domiciliation of T. sordida in the north of
      Minas is recommended where an extensive intervention by man in the natural
      environment has occurred and where a rise in the population of triatomines in the
      peridomestic environment has been observed in recent years.

PMID- 8278754
TI  - Characterization of the non-apparent clinical form in the initial phase of
      schistosomiasis mansoni.
AB  - In this paper the history of 115 recruits that had bathed simultaneously in
      streams contaminated with Schistosoma mansoni, during military maneuvers, is
      reported. Thirty four of the infected patients presented the initial phase of the
      infection diagnosed through epidemiologic, clinical and laboratory parameters.
      Three out of the 34 patients did not reveal the clinical picture of the
      infection, thus being considered representatives of the non-apparent form of the
      disease. Differences between the intensity of blood eosinophilia, the area of
      immediate cutaneous reaction and the number of Schistosoma eggs eliminated in the
      stools proved not to be statistically significant (p > 0.05) when the non
      apparent and acute cases of schistosomiasis were compared. These cases actually
      may be considered evidences of the non-apparent form hitherto merely taken for
      granted in the literature.

PMID- 8278755
TI  - Aggregatory behaviour of platelets incubated with subcellular fractions of normal
      and chagasic human syncytiotrophoblast.
AB  - The surface of human syncytiotrophoblast does not induce maternal blood platelet
      aggregation even though it is not an endothelium. It can be surmised that as
      occurs in endothelial injury the subcellular components of the
      syncytiotrophoblast may have pro- or antiaggregatory activity. During congenital
      Chagas' disease which is associated to trophoblast lesions, platelets may play a
      role in the development of T. cruzi-induced placentitis. In the present work the
      aggregatory behaviour of normal human blood platelets was recorded after their
      challenging with subcellular fractions of syncytiotrophoblast isolated from
      normal and chagasic women. Nuclear, Mitochondrial, Microsomal and Supernatant
      fractions isolated from normal and chagasic syncytiotrophoblast failed to induce
      per se any aggregatory reaction on platelets. When samples of platelet-rich
      plasma (PRP) were preincubated with normal and chagasic nuclear fractions and
      then stimulated with collagen at threshold level (CT-PRP) an inhibition of the
      aggregatory response was observed. Treatment of CT-PRP with normal and chagasic
      mitochondrial fractions induced inhibition of platelet aggregation whereas only
      chagasic fraction reduced latency time. Microsomal fraction from normal placentas
      showed no significant effects on platelet aggregation. It is concluded that
      subcellular fractions of normal human syncytiotrophoblast do not exhibit any
      effect on platelet aggregation, whereas those subcellular fractions enriched in
      intracellular membrane components isolated from chagasic placentas inhibit
      platelet aggregation.

PMID- 8278756
TI  - [Brazilian purpuric fever, virulence in an animal model of Haemophilus aegyptius
      (H. influenzae biogroup aegyptius). Grupo de Estudo da Febre Purpurica
      Brasileira].
AB  - Brazilian purpuric fever (BPF) is caused by invasive strains of Haemophilus
      aegyptius (H. influenzae biogroup aegyptius, Hae). These strains were
      differentiated from Hae strains associated only with conjunctivitis (non-invasive
      Hae strains) through specific molecular markers. Complement-depleted infant rat
      model was used to study the invasive and non-invasive Hae strains to compare
      their virulence potential. Inoculating 10(5) bacteria in the rats, the invasive
      strains caused 80 to 100% bacteremia and the intensity of bacteremia was 10(2.5
      +/- 0.49) to > 10(4.69) cfu/ml of blood. Using the same infectious dose, the non
      invasive strains did not cause frequent bacteremia (0 to 50%) and the intensity
      was 0 to 10(3.69 +/- 0.53) cfu/ml of blood. The infectious doses able to cause
      50% of bacteremia in the rats (BD 50%) varied from < 10(3) to 10(4.2) bacteria
      for the invasive strains, whereas the BD 50% were 10(6.2) to > 10(7.3) bacteria
      for non-invasive strains. Passive immunization using antisera to invasive strains
      protected rats against bacteremia caused by homologous strains, but not by
      heterologous strain. By comparing the bacteremia caused by Hae and bacteremia
      caused by H. influenzae b (Eagan strain, Hib), it was demonstrated that Hib had
      higher virulence potential. This animal model was useful to clarify the virulence
      potential of invasive Hae strains.

PMID- 8278758
TI  - [Rotavirus, adenovirus, astrovirus, calicivirus and small round virus particles
      in feces of children with and without acute diarrhea, from 1987 to 1988, in the
      greater Sao Paulo].
AB  - Between 1987 and 1988, 193 faecal specimens from children, with or without
      diarrhea, were submitted to enzyme immunoassay, polyacrylamide-gel
      electrophoresis and electronmicroscopy tests for virus detection. The positivity
      for Rotavirus, Adenovirus, Astrovirus, Calicivirus and Small Round Virus
      Particles (SRVP) was 11.3%, 3.1%, 2.1%, 1.0% and 4.1%, respectively, for the 97
      children with acute diarrhea. Of the 96 children without diarrhea, 4.2% were
      positive for Rotavirus, 1.0% for Calicivirus and 7.3% for SRVP. Of 15 positive
      specimens for Rotavirus, 14 showed electrophoretic patterns proper to group A and
      1 specimen of group C Rotavirus. The analysis of electrophorotypes demonstrated
      great heterogeneity of electrophoretic patterns and predominance of subgroup 2,
      "long". The association of virus, bacteria and parasites was present both in
      children with or without acute diarrhea.

PMID- 8278757
TI  - The frequency of blood-born viral infections in a population of multitransfused
      Brazilian patients.
AB  - The frequency of viral markers for hepatitis B (HBV) and C (HCV), human
      immunodeficiency virus-1 (HIV-1) and human T-lymphotropic virus-1 (HTLV-1) was
      evaluated in 32 Brazilian beta-thalassemia multitransfused patients. Additionally
      the serum concentrations of ferritin and alanine aspartate transaminase (ALAT)
      were determined. The results show a high prevalence of markers of infection by
      HBV (25.0%) and HCV (46.8%) and a low prevalence of markers for HIV-1 and HTLV-1.
      No correlations were demonstrated between the presence of the hepatitis markers
      and the number of units transfused or the serum concentrations of ferritin and
      ALAT.

PMID- 8278759
TI  - Reduced schedule of human anti-rabies immunization with Fuenzalida & Palacios
      vaccine. Additional data.
AB  - It was reevaluated a reduced schedule for anti-rabies post-exposure immunization
      with newborn mice nervous tissue vaccine (Fuenzalida & Palacios) in a group of 30
      non exposed volunteers. The vaccine was administered by intramuscular injections
      on days zero, 2, 4, 16 and 27, in the deltoid area. Antibody levels were
      determinated by a simplified serum neutralization microtest on days zero, 16 and
      37. On days 16 and 37 the antibody levels of the whole group was > or = 0.5 IU/ml
      and > or = 1.0 IU/ml, respectively. The cell mediated immunity was precociously
      detected (on day 4) by the delayed type hypersensitivity skin test. Our results
      show that this reduced schedule elicited an early and effective humoral and
      cellular immune response. However it is necessary other studies with larger
      groups of vaccinees in order to obtain definitive conclusion.

PMID- 8278760
TI  - Herpes simplex virus type 2 infection in pregnancy: asymptomatic viral excretion
      at delivery and seroepidemiologic survey of two socioeconomically distinct
      populations in Sao Paulo, Brazil.
AB  - The objective of the present study was to estimate the prevalence of herpes
      simplex virus type 2 (HSV 2) antibodies in child bearing women of 2 Brazilian
      populations with different socioeconomic status and to determine the risk of
      neonatal HSV exposure by means of maternal cultures at the onset of labor. The
      study was conducted at 2 hospitals: A, serving very low income patients and B,
      serving middle socioeconomic class. 173 participants from group A and 127 from B
      answered a questionnaire which showed that the patients had similar ages (27.7
      and 26.8 years, respectively) but differed with regard to socioeconomic status,
      age at first intercourse (18.6 vs 20.6 years), number of sex partners (1.5 vs
      1.2) and previous sexually transmitted diseases (15% vs. 1.5%). History of
      genital herpes was given by 11% of group A participants and by a similar number,
      7%, of patients from group B. In addition, 200 serum samples from population A
      and 455 from B were tested by ELISA for anti HSV antibodies and 92% and 86%,
      respectively, were found to be positive. Sixty seropositive samples from group A
      and 90 from B were further analyzed by Western blot, which showed the presence of
      type 2 specific antibodies in 46% and 36%, respectively, suggesting an overall
      HSV 2 prevalence of 42% in group A and 31% in B. Cervical specimens were obtained
      for culture from 299 asymptomatic patients of population A and 313 of B. HSV was
      isolated from one specimen in each group, indicating a 0.3% incidence of
      asymptomatic viral excretion in both populations.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8278761
TI  - Effect of oxamniquine on cell adhesion to Schistosoma mansoni larvae in the
      peritoneal cavity of naive mice.

PMID- 8278762
TI  - African histoplasmosis. Report of the first case in Brazil and treatment with
      itraconazole.
AB  - We report the first case of African histoplasmosis diagnosed in Brazil. The
      patient was an immigrant from Angola who had come to Brazil six months after the
      appearance of the skin lesion. The skin of the right retroauricular area was the
      only site of involvement. The diagnosis was established by direct mycologic
      examination, culture and by histopathologic examination of the lesion. The
      patient was successfully treated with Itraconazole 100mg a day for 52 days. No
      recurrent skin lesions were observed during the ten month follow-up period.

PMID- 8278763
TI  - Vacuum aspiratory puncture system for Leishmania culturing, isolation and
      transport. Preliminary report.

PMID- 8278765
TI  - [Essential rights].

PMID- 8278764
TI  - The causative agent of Jorge Lobo's disease, the fungus P. loboi (= Loboa loboi)
      may be seen extracellularly tightly encircled by histiocytes. Observations at the
      transmission and scanning electron microscopes.

PMID- 8278766
TI  - [A collaborative project of epidemiological research on the quality of care for
      the woman with a tumor. The Collaborative Research Group, the Barin Project].
AB  - The Barin Project aimed at evaluating the quality of health care for women
      affected by breast, ovarian and uterine cancer, using as a measure the
      satisfaction expressed by women. For 2 years women of the Associazione
      Coltivatori Diretti (a rural women association) accepted to report and describe a
      sample of contacts with health services, for any reason (symptoms, controls,
      exams) related, according to the women's perception, to cancer. 3,620 women
      participated in the survey: 2,313 (64%) completed questionnaires only 1,142 (50%)
      of them were of sufficient quality to be analysed. Data were compared with
      figures obtained in a previous survey on the same population and the following
      relevant changes were observed: the number of contacts with the general
      practitioner increased (27% vs 12%) and the number of women who underwent a
      screening almost doubled, with a sensible reduction of the delay due to the woman
      (2 vs 4 weeks of the previous survey). The number of episodes reporting an
      unfavourable evaluation of services and/or health personnel decreased from 41 to
      3.8%.

PMID- 8278767
TI  - [Young nurses grow. The pathways and experiences of nurses newly employed in
      psychiatry].
AB  - Three years after the first interview to a sample of 27 newly employed Registered
      Nurses in the Department of Mental Health, a second interview was administered to
      the nurses still working in the psychiatric services (30% of the original sample
      had already left), to analyze any changes related to their professional
      education, experiences and expectations. 5 of the nurses still remaining would
      like to make a change, while the others (14) expressed very high levels of
      motivation and satisfaction. The structure of the educational curriculum and the
      policy of internal mobility in the different psychiatric services are seen as
      main determinants of what has been observed.

PMID- 8278768
TI  - [For a history of nursing care and nurses in Italy: the indications for research
      on sources and bibliography].
AB  - This is the final article of a series, where main problems and social conditions
      of italian nurses at the beginning of the century were analyzed, and a thorough
      (but not exhaustive) list of the main bibliographic sources is presented.
      Historical research on the recent origins of the nursing profession (beginning of
      the century) can be very awkward and time consuming because many of the original
      sources are not very well known, not readily available and scattered in several
      major and minor libraries and private associations. Knowing what is available and
      what has already been used for historical research can give a further impulse to
      the research and enrich the data base and information on readily available
      sources.

PMID- 8278769
TI  - [Methods and instruments of nursing research: an analysis of some articles].
AB  - Research papers published on some of the most well known foreign nursing journals
      are presented and discussed. The main aim of the contribution, which opens a new
      arena for discussion on the Rivista dell'Infermiere is to critically appraise
      published research works focusing both on strengths and novelty and weaknesses in
      the hypothesis formulation, methods and instruments used, discussion of results.
      A critical analysis should enable nurses to start learn to read and eventually
      write a research protocol, possibly avoiding some common mistakes.

PMID- 8278770
TI  - [The epidemiology and management care of anxiety in nursing practice. The
      Research Group of Matera].

PMID- 8278771
TI  - [Guidelines for the care of the physiologically normal neonate. The Pediatric
      Neonatology Group for Intrahospital Collaboration].

PMID- 8278772
TI  - [The common problems related to the cannulation of a vein].

PMID- 8278773
TI  - [The reform of the health care systems in the world. The debate in medical
      journals].

PMID- 8278774
TI  - [For a discipline of drugs beyond the referendum. The Coordinamento Nazione
      Comunita di Accoglienza (C.N.C.A.), the Italian League for the Fight against AIDS
      (L.I.L.A.), Magistratura Democratica (M.D.) and Psichiatria Democratica (P.D.)].

PMID- 8278775
TI  - [Risk reduction strategies. For a new manner of thinking about drug dependence].

PMID- 8278776
TI  - [The rules of compassion and not just of this].

PMID- 8278777
TI  - [Determining factors of smoking habit and its cessation during pregnancy in a
      urban locality in the southern region of Brazil].
AB  - A cross-sectional study of 873 pregnant women attending a prenatal care clinic
      was undertaken in Pelotas (Southern Brazil), over a one-year period (1989-90) for
      the purpose of identifying possible risk and prognostic factors for smoking
      during pregnancy. The prevalence of smoking at the beginning of pregnancy was
      40.8%. The smoking habits of the woman's mother and partner, as well as her
      educational level, were associated with smoking at the beginning of pregnancy.
      Smoking in the partner was associated with an approximately two-fold increase in
      the risk of smoking. The smoking interruption rate, until the 15th-22nd
      gestational week, was of 35.6%. Family income, smoking habits of woman's mother
      and partner, age at starting, duration and intensity of the woman's habit were
      all associated with the interruption during pregnancy. The above results were not
      affected by adjustment for confounding variables made through stratified
      analysis.

PMID- 8278778
TI  - [Abortion among female students and employees of a Brazilian university].
AB  - In Brazil, the subject of induced abortion is controversial and considered by
      some to be a serious public health problem. On the other hand there are little
      data available as to its frequency and general characteristics. The difficulty
      encountered in obtaining reliable information is to be explained by the
      illegality of abortion that inhibits women from talking about their experience,
      and most studies are carried out in hospitals and thus succeed in identifying
      only those women who have complications. A study was carried out in 1990,
      involving all the female graduate students and employees of a Brazilian
      university. Data was obtained through a questionnaire that was returned by mail,
      anonymously. This paper presents some of the results relating to the frequency of
      miscarriage and abortion in this population. Significantly more students than
      employees were less than 25 years old (85% and 13.7% respectively); fewer
      students were married or in a common-law union (11% of students as against 56% of
      employees) and four times fewer students than employees had never been pregnant
      (15% and 65%). Nine percent of the students and 14% of the employees had had at
      least one abortion. When only sometime pregnant women were taken into
      consideration, over half the students (59%) and 20% of the employees had had an
      abortion. Differences between the two groups were maintained when considered by
      age, both for miscarriage and abortion. Students of less than 25 years of age
      presented the highest percentage of abortion.

PMID- 8278780
TI  - Difficulties encountered in a community-based study of acute respiratory
      infections in Uruguay.
AB  - A cohort study on acute respiratory infections, involving 270 children observed
      by pediatricians in their homes every 10 days over a period of 32 months, gave
      the opportunity to experience logistic and methodological problems seldom
      described in the literature. The purpose of this article is to alert researchers
      as to the difficulties faced when performing community-based studies in
      developing countries. Although a carefully planned project was undertaken,
      problem areas included the establishment of the target population, population
      dynamics, field related problems, laboratory aspects and data management. It is
      hoped that other investigators may benefit from the extensive experience gained
      from our program in foreseeing and coping with the difficulties involved.

PMID- 8278779
TI  - [Presence of Triatoma sordida Stal, 1859 in urban ecotopes, of the city of
      Corrientes, Argentina].
AB  - With the intention of verifying the presence of T. sordida Stal 1859 in urban
      ecotopes in Corrientes city, Argentina, both, human dwellings and an
      extradomiciliary habitat were taken as a basis. A complete T. sordida population
      census was carried on in Mitre Park pigeon house and 400 pigeon nests (Columbia
      livia) were dissected. The triatomineos samples that had been detected in human
      dwellings were sent to the Arthropods Laboratory by their inhabitants. These
      triatomineos were classified systematically and according to their age class.
      Their feces were examined under a microscope 400 x, so as to identify Trypanosoma
      cruzi. Six eggs, 45 first-instar nymphs, 110 second-instar nymphs, 226 third
      instar nymphs, 303 fourth-instar nymphs, 1.103 fifth-instar nymphs, 12 females
      and 11 males were collected from the pigeon house. The presence of this species
      was verified in the 27 houses, situated in 8 different neighborhoods in the city;
      13 eggs, 33 different instar nymphs, 27 females and 9 males were captured, 82
      samples altogether. No triatomineo was infected by T. cruzi. T. sordida adults
      moved towards the houses in Spring and Summer. Of the material found in human
      dwellings 33% was female. The adaptation of T. sordida to extra-domestic habitats
      and their tendency to invade human houses has thus been verified. This fact
      should be taken into account in vector control programs.

PMID- 8278781
TI  - [Grouping of countries according to indicators of standard of living].
AB  - The position of 125 countries is studied on the basis of a collection of 26
      basic, health, economic and educational indicators. Multivariate statistical
      methods were used, including Cluster Analysis, Principal Component Analysis and
      Multivariate Analysis of Variance. The most discriminating variables were life
      expectancy the child mortality rate, the mortality rate of children of less than
      five years of age, the birth and fertility rates and the high-school female
      matriculation rate. The first principal component was interpreted as a measure of
      the living standard which made it possible to place the countries in order. Five
      clusters of countries are suggested.

PMID- 8278782
TI  - [Historical and philosophical elements for a critical analysis of epidemiology].
AB  - The historical and philosophical foundations of epidemiology are examined for the
      purpose of establishing objective bounds for a reflexive analysis as to the
      insertion of this science into today's health practices as a whole. With this in
      view, an epistemological approach, founded upon the Frankfurt School's criticism
      of modern rationality and some theoretical and methodological contributions from
      French School of historical epistemology, is attempted. Historical information
      was obtained from current specialized literature. The abstract notion of
      "environment" in the theoretical translation of "health's public space" is
      emphasized as the contradictory basis for the instrumental shaping of
      epidemiological knowledge. This abstract notion of environment has opened up
      increasing possibilities of knowledge of and practical intervention in sanitary
      phenomena, but has simultaneously restricted the objectivation of the properly
      public character of these phenomena.

PMID- 8278783
TI  - [Hematologic changes in patients chronically exposed to benzene].
AB  - A study was carried out into the hematological abnormalities of peripheral blood
      bone marrow in patients chronically exposed to benzene. The metabolic
      biotransformation and the mechanisms involved in toxicity are described.
      Hematological data are described and discussed. Macrocytosis and lymphopenia are
      the earliest hematological signs of benzene toxicity. Bone marrow abnormalities
      are demonstrated by the complementary methods of cytology and histology. Global
      hypocellularity was mainly due to the granulocytic series. Mastocytosis,
      eosinophilia and magakariocytic abnormalities are also presented. Inflammatory
      abnormalities and signs of dismyelopoiese could also be observed. The importance
      of peripheral blood abnormalities and the need for a critical approach to this
      important public health problem are emphasized.

PMID- 8278784
TI  - [Levels of lead and mercury in the hair of children living in Cubatao, in the
      southeast region of Brazil].
AB  - A study was carried out in 6 districts of Cubatao county, S. Paulo State, Brazil
      on a sample of 251 children aged between 1 and 10. The concentration of heavy
      metals (lead and mercury) in hair was tested. The lead concentration in the hair
      of 229 children was tested, and in 189 (82.5%) levels varying from 2.5 to 71.4
      micrograms/g were detected. The average concentration of the lead found in hair
      was of 7.25 +/- 8.51 micrograms/g. The concentration of mercury in the hair of
      217 children was checked and all of them were found to have levels varying from
      0.2 to 3.0 micrograms/g. The average concentration of mercury was of 0.82 +/-
      0.48 microgram/g. No statistical difference (p > 0.05) was observed between the
      averages found for lead and mercury in the hair of those who consumed and those
      who did not consume aquatic organisms.

PMID- 8278785
TI  - [Profile of the elderly in a metropolitan area of southeastern Brazil: results of
      a domiciliary survey].
AB  - A multicentre study concerned with the health needs of the elderly population
      living in urban areas and coordinated by the Panamerican Health Organization was
      undertaken in 6 Latin-American countries. In Brazil, 1,602 elderly residents (of
      60 years of age and over) in the District of S. Paulo, constituting a multistage
      random sample stratified by socioeconomic status, participated in a household
      survey using a multidemensional functional assessment questionnaire. The results
      showed a highly deprived population (70% had a per capita income of less than US
      $ 100 per month), living mostly in multigenerational households (59% were living
      with children and/or grandchildren), with a high prevalence of chronic physical
      illnesses (only 14% referred no illness) and psychiatric disorders (27% were
      considered psychiatric cases), a high proportion of them showing a loss of
      autonomy (47% needed help in performing at least one of the activities of daily
      living). The results are put into perspective concerning future needs in terms of
      specialized health services and social support for the growing population of
      elderly people in Brazil.

PMID- 8278786
TI  - [Epidemiology of drug consumption in children of a urban center of the southern
      region of Brazil].
AB  - The consumption of medicines among a population-based cohort of 4,746 children
      born in 1982 in Pelotas, Brazil, was studied when the children were aged 3-4.5
      years. Fifty six percent of the mothers reported that their children had taken
      one or more medicines during a two-week period; 29.5% of the products were fixed
      combinations of three or more components, (which was taken as an indicator of
      poor quality). Almost 10% of the children had used a given medicine for one month
      or more. Aspirin, combinations of vitamins and mineral supplements and cough and
      cold combinations were the medicines most frequently used. The commonest reasons
      for taking medicines were colds, fevers and lack of appetite. The latter was the
      commonest reason for long-term use and also for that of combinations. Physician's
      prescriptions were responsible for more than 60% of the medicines used (including
      dipyrone and appetite stimulants). In all social classes the consumption was
      above 50%. Children classified in the fifth quintile of family income consumed
      14% more medicines than the those in the first quintile. Children with two or
      more older siblings consumed 12% less medicines than the elder ones. Malnourished
      children, according to weight for age, consumed 30% more medicines than the well
      nourished. Children consulting a doctor four times or more during the three-month
      period before the interview were using two times more medicines than children who
      had had no consultation during the same period. The frequent use of aspirin is a
      reason for concern as it has been associated with Reye's syndrome in children. It
      is also important to stress the danger of poisoning resulting from medicines
      available at home. Another noteworthy aspect concerns the messages transmitted to
      the children regarding the use of medicines for almost every conceivable reason
      which could possibly lead to medicine or illicit drug addiction.

PMID- 8278787
TI  - [The diagnosis of facial asymmetry].
AB  - Diagnosis of aetiology of facial asymmetry is dependent on results of clinical
      and complementary examinations. Its most frequent causes are illustrated by
      several case reports.

PMID- 8278788
TI  - [Maxillofacial dysmorphosis and myasthenia. Orthodontic and surgical treatment of
      a case].
AB  - Case report of a patient with myasthenia and dysmorphic facial features.
      Pluridisciplinary treatments approach.

PMID- 8278789
TI  - [Tumors of the soft palate and the palatal vault. Our experiences].
AB  - The palate neoplasias are rare and come from either the minor salivary glands or
      the stratified epithelium. The malignant tumors of the hard palate are present 3
      4 times more frequently than the malpighian carcinomas which, on the contrary,
      are prevailing at the soft palate. The malignant tumors of the palate may be
      located or extended to the neighbouring anatomical structures. The application of
      extended surgical operations for their treatment often creates great anatomical
      deficiencies which need the application of a reparatory intervention for
      restoration. We present, in this study, our experience with 6 benign and 8
      malignant tumors of the hard and soft palate that we treated through surgical
      operation.

PMID- 8278790
TI  - [Solitary plasmacytoma. Diagnostic considerations and management attitude apropos
      of a case with mandibular involvement].
AB  - The solitary plasmocytoma of the mandible is a rare affection. This article
      describes the case of a man, 42 years old. A short review of the pathology is
      done. The treatment (surgery and radiotherapy) with their failures and
      complications is exposed.

PMID- 8278791
TI  - [Median cleft of the upper lip. Apropos of 3 cases. The Association for the Study
      of Facial Clefts].
AB  - The authors report three cases of Median Cleft of the upper lip, a clinical
      entity really deserving the term of "hare lip", a very ancient denomination who
      dates back to the Tang Dynasty and unfairly used to describe the usual lateral
      clefts of the lip. The denominations of "true" and "false" median cleft lips
      recovering respectively such different embryopathic realities as clefts of the
      median element with varying degrees of vertical separation and as agenesis of the
      fronto-nasal process accompanied with cerebral anomalies are no more used now.
      Median clefts of the upper lip can be included in the "neurocristopathies" by
      less or more precocious dysneurulation of the fronto-nasal process creating
      anomalies from various single midline defects of the upper lip of our three
      cases, to associated midline defects like in the Median Cleft face syndrome
      (fronto-nasal dysplasia) described by De Myer and Sedano to holoprosencephaly
      (arhinencephaly), which are rarely associated.

PMID- 8278792
TI  - [Rhinorrhea of parotid origin. Apropos of a case].
AB  - The authors report a case of a post-traumatic salivary fistula originating in the
      parotid gland, evacuating into the maxillary sinus and revealed by rhinorrhea.
      The mechanism and treatment of the fistula were analyzed.

PMID- 8278793
TI  - [Surgical treatment of salivary incontinence in cerebral palsy].
AB  - For patients with cerebral palsy, chronic drooling is the result of an
      abnormality in the cerebral control of orofacial motor functions. Sialorrhea is a
      troublesome problem for these patients and their attendants. Among various
      surgical techniques, rerouting of the Stensen's ducts and bilateral excision of
      the submandibular salivary glands, as described by Wilkie, gives good results.
      Transposition of the submandibular gland ducts in the tonsillar fossae is an
      easier procedure but less favorable. We present 19 patients treated by these two
      methods.

PMID- 8278794
TI  - [The contribution of modern medical imaging in post-traumatic carotid-cavernous
      fistula. Apropos of a case].
AB  - Carotid-cavernous fistulas are unusual complications of facial traumas but this
      life-threatening complication requires a rapid diagnosis. Noninvasive procedures
      as ultrasounds will confirm the diagnosis and are helpful to demonstrate
      hemodynamic conditions of the fistula. Angiography remains the main radiologic
      examination and embolization is now the preferred method of treatment. Surgical
      treatment will only be required after failure of the interventional radiology.

PMID- 8278795
TI  - [Bacillary angiomatosis of the oral cavity in AIDS. A differential diagnosis of
      mucosal Kaposi's sarcoma].
AB  - The diagnosis of bacillary angiomatosis (BA) was performed on a biopsy of a
      reddish nodular lesion of the gingival mucosa, in a patient seropositive for the
      H.I.V. It was based on the histopathological features, and by the demonstration
      of bacilli both on the Warthin-Starry stain and the electron microscopic study. A
      treatment by erythromycin was quickly effective. BA is an opportunistic infection
      seen essentially in patients with A.I.D.S., most often causing cutaneous
      involvement. The causative pathogen is Rochalimaea henselae. BA of the oral
      cavity is very rare. This infection can be mistaken with Kaposi sarcoma on its
      clinical appearance.

PMID- 8278796
TI  - [Baldness: indications].
AB  - The author presents his indications for the various types of baldness. Grafts,
      for which the technique used has been recently modified, allow covering small
      patches of alopecia, especially on the anterior frontal line. High-hinged flaps
      are used for more advanced baldness. Lastly, scalp lift and scalp expansion allow
      solving the problem of extensive baldness of the vertex and of the anterior
      frontal line.

PMID- 8278798
TI  - Michigan support for faculty member.

PMID- 8278797
TI  - Italy's role in EMBL.

PMID- 8278799
TI  - Trot and pace.

PMID- 8278800
TI  - NIH AIDS plan: under new management.

PMID- 8278801
TI  - Italy throws EMBL into turmoil.

PMID- 8278802
TI  - Easy-to-alter digital images raise fears of tampering.

PMID- 8278803
TI  - Technology for turning seeing into believing.

PMID- 8278804
TI  - How cells cycle toward cancer.

PMID- 8278805
TI  - Boning up: newly isolated proteins heal bad breaks.

PMID- 8278806
TI  - Polyketide biosynthesis: molecular recognition or genetic programming?

PMID- 8278807
TI  - Hin recombinase bound to DNA: the origin of specificity in major and minor groove
      interactions.
AB  - The structure of the 52-amino acid DNA-binding domain of the prokaryotic Hin
      recombinase, complexed with a DNA recombination half-site, has been solved by x
      ray crystallography at 2.3 angstrom resolution. The Hin domain consists of a
      three-alpha-helix bundle, with the carboxyl-terminal helix inserted into the
      major groove of DNA, and two flanking extended polypeptide chains that contact
      bases in the minor groove. The overall structure displays features resembling
      both a prototypical bacterial helix-turn-helix and the eukaryotic homeodomain,
      and in many respects is an intermediate between these two DNA-binding motifs. In
      addition, a new structural motif is seen: the six-amino acid carboxyl-terminal
      peptide of the Hin domain runs along the minor groove at the edge of the
      recombination site, with the peptide backbone facing the floor of the groove and
      side chains extending away toward the exterior. The x-ray structure provides an
      almost complete explanation for DNA mutant binding studies in the Hin system and
      for DNA specificity observed in the Hin-related family of DNA invertases.

PMID- 8278808
TI  - Built for jumping: the design of the frog muscular system.
AB  - Frogs must generate a high level of mechanical power when they jump. The muscular
      system of frogs that jump is presumably designed to deliver these high powers.
      The length changes and activation pattern that muscles undergo during jumping
      were measured, and isolated muscle bundles were driven through this in vivo
      pattern. During jumping, muscles generated maximum power. Specifically, the
      muscle fibers (i) operated at optimal sarcomere lengths, (ii) operated at optimal
      shortening velocities, and (iii) were maximally activated during power
      generation. Thus, many different parameters must have evolved in concert to
      produce a system capable of this explosive jumping movement.

PMID- 8278809
TI  - Benefit to male sailfin mollies of mating with heterospecific females.
AB  - Female gynogens reproduce clonally but rely on sperm from heterospecific males to
      initiate embryogenesis. It has been assumed that males gain no benefit from such
      matings; thus, selection should favor males that avoid them. Here it is shown
      that males gain a benefit by mating with female gynogens in an asexual-sexual
      complex of fish. The sexual females increase their preference for males whom they
      observe consorting with female gynogens. Thus, gynogenetic species might persist
      because selection favors males to be sexually parasitized.

PMID- 8278810
TI  - Structure of the catalytic domain of fibroblast collagenase complexed with an
      inhibitor.
AB  - Collagenase is a zinc-dependent endoproteinase and is a member of the matrix
      metalloproteinase (MMP) family of enzymes. The MMPs participate in connective
      tissue remodeling events and aberrant regulation has been associated with several
      pathologies. The 2.4 angstrom resolution structure of the inhibited enzyme
      revealed that, in addition to the catalytic zinc, there is a second zinc ion and
      a calcium ion which play a major role in stabilizing the tertiary structure of
      collagenase. Despite scant sequence homology, collagenase shares structural
      homology with two other endoproteinases, bacterial thermolysin and crayfish
      astacin. The detailed description of protein-inhibitor interactions present in
      the structure will aid in the design of compounds that selectively inhibit
      individual members of the MMP family. Such inhibitors will be useful in examining
      the function of MMPs in pathological processes.

PMID- 8278811
TI  - Stereospecific acyl transfers on the erythromycin-producing polyketide synthase.
AB  - During assembly of complex polyketide antibiotics like erythromycin A, molecular
      recognition by the multienzyme polyketide synthase controls the stereochemical
      outcome as each successive methylmalonyl-coenzyme A (CoA) extender unit is added.
      Acylation of the purified erythromycin-producing polyketide synthase has shown
      that all six acyltransferase domains have identical stereospecificity for their
      normal substrate, (2S)-methylmalonyl-CoA. In contrast, the configuration of the
      methyl-branched centers in the product, that are derived from (2S)-methylmalonyl
      CoA, is different. Stereoselection during the chain building process must,
      therefore, involve additional epimerization steps.

PMID- 8278812
TI  - Rational design of potent, bioavailable, nonpeptide cyclic ureas as HIV protease
      inhibitors.
AB  - Mechanistic information and structure-based design methods have been used to
      design a series of nonpeptide cyclic ureas that are potent inhibitors of human
      immunodeficiency virus (HIV) protease and HIV replication. A fundamental feature
      of these inhibitors is the cyclic urea carbonyl oxygen that mimics the hydrogen
      bonding features of a key structural water molecule. The success of the design in
      both displacing and mimicking the structural water molecule was confirmed by x
      ray crystallographic studies. Highly selective, preorganized inhibitors with
      relatively low molecular weight and high oral bioavailability were synthesized.

PMID- 8278813
TI  - Regulation of MHC class I transport by the molecular chaperone, calnexin (p88,
      IP90).
AB  - Assembled class I histocompatibility molecules, consisting of heavy chain, beta 2
      microglobulin, and peptide ligand, are transported rapidly to the cell surface.
      In contrast, the intracellular transport of free heavy chains or peptide
      deficient heavy chain-beta 2-microglobulin heterodimers is impaired. A 90
      kilodalton membrane-bound chaperone of the endoplasmic reticulum (ER), termed
      calnexin, associates quantitatively with newly synthesized class I heavy chains,
      but the functions of calnexin in this interaction are unknown. Class I subunits
      were expressed alone or in combination with calnexin in Drosophila melanogaster
      cells. Calnexin retarded the intracellular transport of both peptide-deficient
      heavy chain-beta 2-microglobulin heterodimers and free heavy chains. Calnexin
      also impeded the rapid intracellular degradation of free heavy chains. The
      ability of calnexin to protect and retain class I assembly intermediates is
      likely to contribute to the efficient intracellular formation of class I-peptide
      complexes.

PMID- 8278814
TI  - Retention of unassembled components of integral membrane proteins by calnexin.
AB  - Quality control mechanisms prevent the cell surface expression of incompletely
      assembled multisubunit receptors such as the T cell receptor (TCR). The molecular
      chaperone function of calnexin (IP90, p88), a 90-kilodalton protein that resides
      in the endoplasmic reticulum (ER), in the retention of representative chains of
      the TCR-CD3 complex in the ER was tested. Truncation mutants of calnexin, when
      transiently expressed in COS cells, were exported from the ER and either
      accumulated in the Golgi or progressed to the cell surface. CD3 epsilon chains
      cotransfected with the forms of calnexin that were not retained in the ER exited
      the ER and colocalized with calnexin. Since engineered calnexin determined the
      intracellular localization of the proteins associated with it, it is concluded
      that calnexin interacts with incompletely assembled TCR components and retains
      them in the ER.

PMID- 8278815
TI  - Inverting the therapeutic pyramid: observations and recommendations on new
      directions in rheumatoid arthritis therapy based on the author's experience.
AB  - In evaluating current therapy for rheumatoid arthritis (RA), it is increasingly
      being recognized that sequential single-drug treatment, as exemplified by the
      traditional therapeutic pyramid, is often too little, too late, and ineffective
      in preventing disease progression or joint damage in patients with "at-risk,"
      aggressive synovitis or what might be called type 2 RA. Designation of drugs as
      either antiinflammatory or disease-modifying is not supported by the author's
      experience. Evidence exists that prevention of joint damage correlates best with
      control of clinical and laboratory measures of inflammation, regardless of the
      medication used. The earlier and more effective the control of the inflammation,
      the better the patient response. Until a major breakthrough occurs, the author
      recommends that patients with aggressive RA be treated with a combination of fast
      acting and slow-acting medications to achieve early control and then "bridge
      down" to a simplified maintenance program. Retrospective observation by the
      author of 54 patients with early, intermediate, and late disease treated with
      combinations of prednisone, methotrexate, auranofin, hydroxychloroquine, and
      azathioprine showed maximum response in patients with disease duration of less
      than 2 years, minimal toxicity, and lack of erosions in patients with control of
      inflammation. Twelve patients with inflammation not initially suppressed by
      prednisone and methotrexate had improved control with additional drugs in
      combination, including auranofin, hydroxychloroquine, and azathioprine. After
      inflammation was controlled, reduction of prednisone and methotrexate doses was
      possible in 60% of patients, primarily those with early disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8278816
TI  - Limitations of randomized clinical trials to recognize possible advantages of
      combination therapies in rheumatic diseases.
AB  - Potential advantages of combination second-line drug therapy in rheumatoid
      arthritis (RA) may not be detectable in standard randomized controlled clinical
      trials, despite excellent design and performance. This results from intrinsic
      limitations of usual clinical studies, such as a short time frame, patient
      selection, and insufficient numbers of patients. Examples of selected clinical
      protocols in rheumatic diseases that illustrate these problems are presented. In
      systemic lupus erythematosus, many well-designed and -performed trials comparing
      combinations of cytotoxic drugs and corticosteroids with corticosteroids alone
      were inconclusive. However, combination therapy was superior in three types of
      studies: a 15-year clinical trial, a pooled analysis of multiple trials, and
      longitudinal databases of unselected patients. In RA, a 48-week study indicated
      no differences in results of treatment with auranofin, methotrexate, and the
      combination of these two drugs. In contrast, a clinical database from 15
      rheumatology practices indicates that methotrexate was continued for 5 years by
      more than 50% of patients, compared with fewer than 10% for auranofin. A subset
      from the clinical database of courses of second-line drugs over 1 year (rather
      than 5 years), for only the initial course of a second-line drug (rather than any
      course), was examined. Using these selected data, which mimic the conditions of
      the clinical trial, no significant differences were seen in continuation of
      methotrexate versus auranofin. This observation suggests that intrinsic
      limitations, including patient selection, insufficient patient numbers, and a
      short time frame, may render it difficult (or impossible) to document the
      efficacy of combination therapy in RA using standard randomized controlled
      clinical trials.

PMID- 8278818
TI  - Personal experience in the treatment of seropositive rheumatoid arthritis with
      drugs used in combination.
AB  - Drug therapy for seropositive rheumatoid arthritis (RA) is entirely empiric.
      Single agents often fail to control synovial inflammation adequately. Combination
      therapy with relatively small doses of several agents shown to be effective in
      controlled trials when used alone often produce sustained and marked therapeutic
      control. Adverse effects are frequent but probably are no greater than those
      associated with the use of an effective dose of a single agent. As in the
      treatment of malignancy or tuberculosis, the use of potent drugs in combination
      may prevent or delay the clonal expansion of resistant cells. If this is indeed
      the case in the treatment of RA, then consideration should be given to the
      routine use of drug combinations. It is conceivable that we do patients a
      disservice by using potentially valuable drugs sequentially rather than in
      tandem. Whatever its merits, combination drug therapy for seropositive RA is
      clearly a stopgap measure whose usefulness will end as more specific means of
      controlling joint inflammation become available.

PMID- 8278817
TI  - Early, aggressive therapy for rheumatoid arthritis: concerns, descriptions, and
      estimate of outcome.
AB  - The past few years have witnessed changing perceptions about rheumatoid arthritis
      (RA); it is now considered a serious systemic disease that confers not only
      physical and social morbidity but also earlier mortality. The long-term outcome
      of sequential monotherapy based on the therapeutic pyramid has been
      disappointing. A review of prognostic factors, acute disease activity measures,
      functional measures, and the results of preliminary trials with combination
      therapy suggests that specific goals of treatment can be established and that
      logical, aggressive treatment in early disease can be accomplished. These goals
      should include prompt control and continuous reduction of the active joint count
      to < or = 4 and normalization of acute-phase reactants. The "graduated-step
      paradigm" of treatment designed with these goals in mind is described, and a
      retrospective series that gives an estimate of outcome with its use is reported.

PMID- 8278819
TI  - Comparing the strengths and weaknesses of observational and experimental studies
      using a postmarketing surveillance study as a protypic example.
AB  - A recent prospective, observational study in rheumatoid arthritis patients
      indicated that the addition of hydroxychloroquine to either aspirin or
      methotrexate therapy decreased the incidence of hepatic enzyme abnormalities.
      This interesting finding is of potential clinical importance, but its validity
      needs to be examined in terms of the potential confounders inherent in
      observational studies. Although one of the study's strengths is its derivation
      from "real-life" data, some potential confounders that might weaken the data
      include a need to examine whether any scientific rationale can be discerned for
      the observation; examination of control-case matching (issues of randomization
      and baseline disease characteristics); the potential for attribution bias; data
      collection methods (prospective versus retrospective, uniform versus chart
      review); and equivalency of treatment protocols, dosing regimens, and concomitant
      medications. Potential scientific rationale exists for the observed interaction,
      and data collection is both uniform and prospective. These strengths are
      confounded by the inevitable lack of randomization in observational studies, the
      potential for differences in baseline disease characteristics, attribution bias,
      a lack of controlled dosing regimens and treatment protocols, and an assumption
      that all nonsteroid antiinflammatory drugs are alike (which is not true). On
      balance, the hypothesis generated by these data is compelling enough to deserve
      further testing in both observational and experimental settings.

PMID- 8278820
TI  - The ocular safety of hydroxychloroquine.
AB  - The insert currently supplied with hydroxychloroquine states that patients should
      have an initial ophthalmological assessment and then regular assessments every 3
      months. The rheumatologist should expect a report from the ophthalmologist, which
      includes a corneal assessment of tissue dose, a reference to visual field defects
      if present on the Amsler grid, and a comment concerning the status of the
      patient's color vision. Daily dose is more important than duration of dose,
      regarding maculopathy. The visual prognosis of retinopathy is excellent if the
      diagnosis is made at an early stage of the disease. This report suggests that
      ophthalmological review need only occur initially and on a yearly basis if the
      daily dose of hydroxychloroquine is less than 6.5 mg/kg/d and the duration of
      therapy is less than 9 years.

PMID- 8278821
TI  - The relative toxicity of alternative therapies for rheumatoid arthritis:
      implications for the therapeutic progression.
AB  - The traditional pyramid for the therapeutic progression in rheumatoid arthritis
      (RA) is based on assumptions that RA is a mild disease, that nonsteroidal
      antiinflammatory drugs (NSAIDs) have low toxicity, and that disease-modifying
      antirheumatic drugs (DMARDs) are extremely toxic. This article reviews data from
      ARAMIS (Arthritis, Rheumatism, and Aging Medical Information System), casting
      strong doubt on these assumptions. NSAIDs result in 1.3% excess gastrointestinal
      hospitalizations per year. Mortality rates in RA are far above those expected
      from age- and sex-matched populations. Individual NSAIDs show widely different
      overall quantitative toxicity indices, as do individual DMARDs. However, the
      ranges of toxicity of the two classes of drugs show nearly complete overlap. It
      is suggested that the new therapeutic progression in RA should emphasize initial
      use of DMARDs, beginning with the least toxic.

PMID- 8278822
TI  - Determination of the stereoisomers of hydroxychloroquine and its major
      metabolites in plasma and urine following a single oral administration of racemic
      hydroxychloroquine.
AB  - Plaquenil (hydroxychloroquine, HCQ; Sanofi Winthrop Pharmaceuticals, New York,
      NY) is a stereoisomeric drug administered as a racemic (50: 50) mixture of two
      isomeric forms--(+) and (-) HCQ. To correlate clinical efficiency accurately with
      dose, it is necessary to determine the fate of both isomers. This will allow for
      the optimization of clinical dosing. A method has been developed for the
      quantitation of (+) and (-) HCQ and its major metabolites,
      desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and
      bisdesethylchloroquine (BDCQ), in plasma and in urine. Application of this method
      in a preliminary study in four human volunteers is reported. After a single oral
      dose of 200 mg of Plaquenil, the average enantiomeric ratio of (+) to (-) HCQ was
      approximately 1 over an 8-hour period. However, the average cumulative 48-hour
      excretion of HCQ, DHCQ, and DCQ showed stereoselective excretion.

PMID- 8278823
TI  - Mechanism of action of hydroxychloroquine as an antirheumatic drug.
AB  - The antimalarial agents chloroquine and hydroxychloroquine have been used widely
      for the treatment of rheumatoid arthritis and systemic lupus erythematosus. These
      compounds lead to improvement of clinical and laboratory parameters, but their
      slow onset of action distinguishes them from glucocorticoids and nonsteroidal
      antiinflammatory agents. Chloroquine and hydroxychloroquine increase pH within
      intracellular vacuoles and alter processes such as protein degradation by acidic
      hydrolases in the lysosome, assembly of macromolecules in the endosomes, and
      posttranslation modification of proteins in the Golgi apparatus. It is proposed
      that the antirheumatic properties of these compounds results from their
      interference with "antigen processing" in macrophages and other antigen
      presenting cells. Acidic cytoplasmic compartments are required for the antigenic
      protein to be digested and for the peptides to assemble with the alpha and beta
      chains of MHC class II proteins. As a result, antimalarials diminish the
      formation of peptide-MHC protein complexes required to stimulate CD4+ T cells and
      result in down-regulation of the immune response against autoantigenic peptides.
      Because this mechanism differs from other antirheumatic drugs, antimalarials are
      well suited to complement these other compounds in combination drug therapy.

PMID- 8278824
TI  - An international challenge to the diagnosis and treatment of disorders of the
      lumbar spine.
AB  - Since its formation 20 years ago, the International Society for Study of the
      Lumbar Spine has stimulated basic and clinical research. Because few disorders of
      the lumbar spine are lethal, our usual goal is to improve the quality of life of
      our patients by relieving pain and improving function. To do so, we must
      continuously improve the quality of the preventive, diagnostic, and treatment
      methods we employ. If quality is our goal, we need to be precise in our
      definition, understand how we measure it, and most importantly, be explicit in
      how we will improve it. Also, we must understand that our work is being conducted
      in a shrinking world, where all industrialized nations are profoundly concerned
      about the costs of health care.

PMID- 8278825
TI  - Practice variations, treatment fads, rising disability. Do we need a new clinical
      research paradigm?

PMID- 8278826
TI  - The effect of torque pressure on halo pin complication rates. A randomized
      prospective study.
AB  - At Thomas Jefferson University Hospital, 102 consecutive patients treated in a
      halo vest orthosis were randomized into one of two torque protocol groups based
      on their date of birth. The pins of patients who were born in even-numbered
      months were inserted with 8 inch-lbs of torque and those born in odd-numbered
      months were inserted with 6 inch-lbs. All patients were placed in an identical
      model halo using a standardized technique of application. The patients were
      followed prospectively, and all potential complications were evaluated by a
      member of the orthopedic attending staff, using protocols established at the
      onset of the study. Statistical analysis indicated no significant differences in
      halo pin loosening, infection, pain, or scarring between the torque protocols,
      but there was a trend toward a higher complication rate in the 8-inch-lbs group.
      There was no direct evidence of skull penetration in either group, and no
      patients developed a deep infection. Based on the results of this study, we
      conclude that insertion torque has no significant effect on halo pin
      complications within the ranges tested by this study. Our current protocol calls
      for routine insertion of halo pins with 6 inch-lbs of torque.

PMID- 8278827
TI  - Late radiographic findings after anterior cervical fusion for spondylotic
      myeloradiculopathy.
AB  - A retrospective study was performed to evaluate the radiographic changes that
      occurred at spinal levels adjacent to fused vertebrae after anterior cervical
      fusion. One hundred six patients with cervical spondylotic myeloradiculopathy (88
      men, 18 women) were followed for an average of 8.5 years. The average age at
      follow-up was 64 years. Forty-two patients underwent a single-level fusion, 52
      had a two-level fusion, and 12 had three levels fused. Seventeen patients who
      underwent additional surgery after anterior fusion also were reviewed, with an
      average follow-up period of 2.9 years. Postoperatively, cervical flexion
      extension resulted in significantly increased movement about the vertebral
      interspace at the upper adjacent level. An increment of posterior slip of the
      vertebra immediately above the fusion level, with associated spinal canal
      compromise of less than 12 mm, significantly affected neurologic results.
      Patients with multilevel fusions notably exhibited these radiographic
      abnormalities at adjacent levels. Spinal canal stenosis, when associated with
      dynamic spinal canal stenosis in the vertebra above the fusion level, affected
      late neurologic results. Results of salvage laminoplasty were not satisfactory.
      Unnecessarily extended longer fusion must be avoided.

PMID- 8278828
TI  - Calcium crystal deposition in the ligamentum flavum of the cervical spine.
AB  - This article reports eight patients who underwent posterior decompressive surgery
      for myeloradiculopathy caused by calcium crystal deposition in the ligamentum
      flavum of the cervical spine. All were women with an average age of 72 years and
      showed neurologic improvement postoperatively. Four patients had diabetes
      mellitus, and knee meniscus calcification on radiographs were noted in four
      patients. The ligamentum flavum of C5-6 and C6-7 were sites frequently involved.
      Crystallographic examination confirmed resected deposits as calcium pyrophosphate
      dihydrate crystal in all patients and additional hydroxyapatite crystal in two.
      Histology confirmed marked degeneration in elastic fibers about the calcium
      deposits. This pathologic condition is possibly spinal manifestation of systemic
      calcium crystal deposition disease.

PMID- 8278829
TI  - Scapulohumeral reflex (Shimizu). Its clinical significance and testing maneuver.
AB  - Searching for a muscle stretch reflex that is innervated by the high cervical
      cord, the authors discovered the scapulohumeral reflex (Shimizu)--SHR (Shimizu).
      The testing maneuver, localization of the reflex center, its clinical
      significance, and the designation of the SHR (Shimizu) are dealt with in this
      report. The SHR is elicited by tapping the tip of the spine of the scapula and
      acromion in a caudal direction. The SHR is classified as hyperactive only when an
      elevation of the scapula or an abduction of the humerus have been clearly defined
      after tapping at these points. Two hundred twenty-five patients with cervical
      spine disorders, 90 normal individuals, and 17 patients with cerebrovascular
      strokes were examined. The incidence of hyperactive SHR was highest among several
      neurologic abnormalities in spastic cases with craniovertebral or high cervical
      lesions, and all cases with hyperactive SHR in the cervical spine disorder group
      exhibited neural compressive factors at the high cervical region. The major
      muscles participating in the SHR are considered to be the upper portion of the
      trapezius, the levator scapulae, and the deltoid. According to the anatomic level
      of compressive factors and the postoperative course of the activity in
      hyperactive SHR cases, the reflex center of the SHR is clinically presumed to be
      located between the posterior arch of C1 and the caudal edge of the C3 body.
      Hyperactive SHR provides useful information about dysfunctions of the upper motor
      neurons cranial to the C3 vertebral body level.

PMID- 8278830
TI  - Noninvasive measurement of cervical tri-planar motion in normal subjects.
AB  - An electronic digital inclinometer was used to obtain normative data on cervical
      mobility from 58 normal subjects. They consisted of 28 males (age range, 17-61)
      and 30 females (age range, 19-62). The measurements were taken from occiput to T1
      in flexion-extension, lateral bend, and axial rotation, isolating the regional
      motion by measuring simultaneously the upper and lower margins of the eight
      mobile segments. A comparison of radiographs and inclinometer measures showed
      excellent correlations (r < 0.9997, P < 0.05). Normative data are presented.
      Gender-specific regional mobility differences occurred only in cervical
      extension, whereas no consistent age-related differences were found. Stiffer
      individuals could be found in either gender or any age group, but rigidity in one
      plane did not necessarily predict rigidity in another.

PMID- 8278831
TI  - Repeat lumbar spine surgery. Factors influencing outcome.
AB  - Forty-five patients who had residual symptoms after lumbar spine surgery were re
      evaluated and underwent additional surgery. After a minimum of 2 years' follow
      up, these patients' results were reviewed to determine what variables might
      predict long-term outcome. Age, number of previous operations, and psychological
      diagnosis were not statistically significant, but a non-compensable injury,
      ability to return to work after surgery, a negative history of litigation, and
      achieving a solid fusion were statistically significant in predicting a good
      outcome. In this study of 45 patients who had repeat surgery, 82% were improved
      at an average follow-up of 28.2 months. Intrathecally enhanced computed
      tomography, magnetic resonance imaging, discography, and computed tomography
      discography are required to thoroughly evaluate the previously operated lumbar
      spine, because a single imaging study showed surgical abnormalities in only 61%
      of the patients in this study.

PMID- 8278832
TI  - Residual gait abnormalities in surgically treated spondylolisthesis.
AB  - The authors retrospectively studied seven patients who had in situ fusion as
      adolescents for high-grade (IV, V) spondylolisthesis unresponsive to more
      conservative means. All patients achieved solid bony union; their pain was
      relieved; and hamstring spasm had resolved. The authors sought to determine
      whether crouch gait or any other abnormalities could be demonstrated in patients
      exhibiting clinical parameters of success. Each patient underwent gait analysis,
      radiographic analysis, and a physical examination. Four of seven patients
      demonstrated slight degrees of forward trunk lean during varying phases of gait
      accompanied by increased hip flexion. One patient demonstrated increased trunk
      extension accompanied by limited hip flexion. Two patients were essentially
      normal. The authors were unable to quantify residual crouch in these patients
      with solidly fused high-grade spondylolisthesis.

PMID- 8278833
TI  - Microdiscectomy and second operation for lumbar disc herniation.
AB  - To prevent recurrence and avoid the second operation, the authors analyzed the
      clinical features and surgical outcome of 214 patients (157 males and 57 females)
      who underwent lumbar microdiscectomy, 16 of whom required second operation. The
      mean age was 34.6 years (range, 12-62 years). The average follow-up period was 4
      years 5 months. The overall incidence of second operation was 7.5%. Second
      operation was performed because of recurrence of herniation in nine patients, and
      residual bony compression at the lateral recess in two. The incidence of second
      operation was significantly higher in teenagers than in patients in other age
      decades (P < 0.01), and in patients with protrusion-type herniation than in those
      with extrusion-type or sequestration-type herniation (P < 0.01). To prevent the
      necessity for second operation, careful and thorough discectomy, especially deep
      to the posterior longitudinal ligament, and decompression at the lateral recess
      are useful.

PMID- 8278834
TI  - Percutaneous nucleotomy in lumbar disc herniation. Patient selection and role in
      various treatments.
AB  - Patients in percutaneous nucleotomy who met our new criteria for patient
      selection in 1992 showed 73% successful results. The success rate was not
      satisfactory in comparison with that (88%) in the open surgery through posterior
      approach (herniotomy), however. The purpose of this report is to re-evaluate 70
      patients with follow-up more than 2 years based on imaging and clinical findings
      before percutaneous nucleotomy. In results, supplementary criteria such as two
      types of the combination of computed tomography discogram and computed tomography
      myelogram, continuation of the contrast medium in lateral view of discogram, and
      clinical findings characterized by sciatic pain were obtained to improve the
      success rate. Eighty-one percent of patients who met the new criteria in 1992 and
      the supplementary criteria were identified in the successful group. The authors
      believe that percutaneous nucleotomy should be considered as an independent
      operative procedure with results similar to open surgery, if the patient is
      selected strictly based on these criteria and supplementary criteria.

PMID- 8278835
TI  - Percutaneous discectomy in athletes.
AB  - Percutaneous discectomy has been widely used for the lumbar disc herniation in
      recent years because it is a simple and safe procedure. This report evaluates the
      postoperative return to the original level of activity among athletes who compete
      in their sports on a national level. It has been thought that the recovery rate
      was poor in the conventional surgery but there have been few studies. The
      postoperative results using percutaneous discectomy were rated as excellent in 4
      athletes, good in 5, poor in 4. The patients generally returned to full sports
      activity 2 months after surgery. The authors conclude that percutaneous
      discectomy may be considered if conservative treatments fail to relieve pain in
      athletes.

PMID- 8278836
TI  - Comparison of operative results of lumbar disc herniation in manual laborers and
      athletes.
AB  - The results of various surgical treatments for lumbar disc herniation in laborers
      and athletes were compared on the basis of the relative success of return to work
      and athletic activity. The rate of successful return to manual labor was the
      highest at 89% after spinal fusion, but no difference was observed between simple
      disc excision and percutaneous discectomy. Return to competitive sports was
      achieved at rate of 81% after percutaneous discectomy, and the time until return
      to sports activity was significantly shorter than after other procedures. In
      individuals whose lumbar region is expected to be subjected to great mechanical
      stress, it is important to take work needs and the special needs of athletes into
      consideration when selecting the surgical procedure.

PMID- 8278837
TI  - Vascular injury in anterior lumbar surgery.
AB  - Anterior approaches to the lumbar spine are rapidly gaining popularity for
      decompressive and reconstructive procedures. A recognized hazard to this approach
      to the spine is possible injury to the great vessels. This retrospective study is
      a review of 102 consecutive anterior lumbar spinal procedures. All approaches
      were performed by one of two fellowship-trained vascular surgeons. Both have
      extensive experience with this approach. All injuries to the inferior vena cava,
      common iliac vein, or other great vessels that required suture repair were
      recorded. The authors were surprised to note an overall rate for this vascular
      complication of 15.6%. These injuries included 11 tears of the common iliac vein,
      four tears of the inferior vena cava, and one avulsion of the iliolumbar vein.
      Two different approaches were used during this study. Twenty-six cases were
      performed through a flank incision, with the dissection proceeding through the
      external and internal oblique muscles as well as the transversus abdominis. The
      average number of levels exposed was 2.3. Two vascular complications resulted,
      for an incidence of 7.7%. Seventy-six procedures were carried out through a small
      (5-10 cm) incision overlying the rectus abdominis muscle. The retroperitoneal
      space was entered through the posterior rectus sheath without division of any
      muscle tissue. This resulted in 14 vascular complications, for an incidence of
      18.4%. Although the authors are unaware of any major long-term morbidity from
      this complication in their patient group, they believe feel that the true
      incidence of this potentially quite serious complication may be
      underestimated.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278838
TI  - Complications associated with the technique of pedicle screw fixation. A selected
      survey of ABS members.
AB  - A limited survey analysis of 617 surgical cases in which pedicle screw implants
      were used was undertaken to ascertain the incidence and variety of associated
      complications. The different implant systems used included variable spinal
      plating (n = 249), Edwards (n = 143), and AO fixateur interne (n = 101). The most
      common intraoperative problem was unrecognized screw misplacement (5.2%).
      Fracturing of the pedicle during screw insertion and iatrogenic cerebrospinal
      fluid leak occurred in 4.2% of cases. The postoperative deep infection rate was
      4.2%. Transient neuropraxia occurred in 2.4% of cases, and permanent nerve root
      injury occurred in 2.3% of cases. Previously unreported injury to nerve roots
      occurred late in the postoperative course in three cases. Screw breakage occurred
      in 2.9% of cases. All other complications had an incidence of less than 2%. The
      authors conclude that pedicle screw placement may be associated with significant
      intraoperative and postoperative complications. This information is of value to
      surgeons using pedicle implant systems as well as to their patients. Repeat
      surgery is associated with greater numbers of complications.

PMID- 8278839
TI  - Stability of transpedicle screwing for the osteoporotic spine. An in vitro study
      of the mechanical stability.
AB  - The influence of bone mineral density on the stability of transpedicle screwing
      was studied in the human cadaveric lumbar vertebrae. The pull-out force
      correlated with bone mineral density. The tilting moment (load needed to tilt the
      screw 4 degrees cranially at the screw-plate junction) and the cut-up force (load
      needed to tip the end plate up by the screw) correlated with bone mineral
      density. A correlation was also found between the maximum insertion torque of the
      screw and bone mineral density. The maximum insertion torque correlated with the
      pull-out force, the tilting moment, and the cut-up force. In the cyclic tilting
      test (200 cycles), the mean value of the tilting moment at the 200th cycle was
      67.4 +/- 6.1%, compared with the first cycle. The results suggest that
      preoperative measurement of BMD is necessary for transpedicle screwing in
      osteoporotic cases, and that the cyclic tilting motion decrease its mechanical
      stability. The authors have also concluded that the maximum insertion torque
      could predict the mechanical stability.

PMID- 8278840
TI  - An anatomic study of foraminal nerve root lesions in the lumbar spine.
AB  - An anatomic study of lumbar nerve root lesions in the foraminal zone was
      performed on 35 cadavers. Two morphologic abnormalities of the nerve roots in the
      intervertebral foramen were found. The first was an abnormal transverse course of
      the nerve roots. The second was an indentation on the dorsal root ganglia caused
      by compression of the superior articular facet, degenerative bulging discs, or
      both. The incidence of indentation on the dorsal root ganglia was dependent on
      location of the ganglia or age. For details, at the L5 root level, the ganglia
      located in the proximal part of neuroforamen had the highest incidence, and
      extraforaminally located ganglia have the lowest incidence of indentation. The
      incidence of indented dorsal root ganglia increased with age. The possible
      correlation between these observed anatomic abnormalities and clinical symptoms
      must be further elucidate.

PMID- 8278841
TI  - Mechanosensitive afferent units in the lumbar intervertebral disc and adjacent
      muscle.
AB  - The purpose of this study was to characterize the somatosensory units of the
      lumbar intervertebral disc and adjacent muscle. A laminectomy was performed on
      the lumbar spine of adult male Japanese White rabbits. Receptive fields of
      mechanosensitive afferent units were investigated in the intervertebral disc and
      adjacent muscle, and electrophysiologic recordings were obtained from filaments
      of the dorsal root. Thirteen mechanosensitive units were identified: three units
      in the intervertebral disc area, and 10 units in the psoas muscle. Of the three
      units in the disc area, one was identified at the surface of the L5-6 anulus
      fibrosus and two at the insertion of the anulus fibrosus to the L5 and L6
      vertebral bodies. These three units belonged to Group III and had very high
      mechanical thresholds, more than 160 g. The 10 units in the psoas muscle belonged
      to Groups II, III, and IV, and had mechanical thresholds ranging from 0.22 to
      12.6 g. The units in the disc area may serve as nociceptors sensitive to strong
      noxious stimulation that could traumatize the tissue. The units in the psoas
      muscle may contribute to nociception and proprioception.

PMID- 8278842
TI  - Alkaline phosphatase as a biochemical maturity index in female adolescence.
AB  - The relationship between alkaline phosphatase activity and conventional bone
      maturity factors (chronologic age, half-yearly and yearly height increases),
      Risser sign, menarche, and the number of months elapsed after menarche) was
      analyzed in 276 female patients with scoliosis, ages 9 to 17 years. Alkaline
      phosphatase showed a very high correlation with these maturity factors.
      Incorporation of the alkaline phosphatase evaluation in the idex for assessing
      the bone maturity or residual physical growth in adolescent females may enable
      physicians to make a more accurate clinical assessment. [Classifying (normal: 10
      unit (U) by Kind-King method): Group 1 (> 25 U) and Group 2 (25 U > or = > 20 U)
      as the growth period, Groups 3 and 4 (20 U > or = > 10 U) as the growth
      transition period, and Group 5 (10 U > or =) as the growth completion period]

PMID- 8278843
TI  - Age-related changes in proteoglycans of human ligamentum flavum.
AB  - Age-related changes in proteoglycans of human ligamentum flavum were studied
      using specimens obtained from patients divided into four age groups. The
      proteoglycans were purified by ion-exchange and gel-filtration chromatography. A
      low-molecular-weight proteoglycan with the same molecular size was present in all
      each age groups. Conversely, high-molecular-weight proteoglycan increased with
      advancing age. Properties of the sugar chains, glycosaminoglycans, in these
      proteoglycans were studied using cellulose acetate membrane electrophoresis and
      chondroitinase digestion. It was found that the high-molecular-weight
      proteoglycan consisted mainly of chondroitin 6-sulfate, whereas the low-molecular
      weight proteoglycan consisted mainly of dermatan sulfate, although the ratio of
      chondroitin 6-sulfate increased with age. These results indicate that
      proteoglycans of human ligamentum flavum show changes in amount and composition
      with age.

PMID- 8278844
TI  - Elevated plasma fibronectin concentrations in patients with ossification of the
      posterior longitudinal ligament and ossification of the ligamentum flavum.
AB  - Fibronectin is a glycoprotein involved in a wide variety of cellular activities,
      including the development of bone tissues. To study the relevance of fibronectin
      to the development of ossification of the posterior longitudinal ligament (OPLL)
      and ossification of the ligamentum flavum (OLF), plasma fibronectin
      concentrations in 30 consecutive patients with OPLL or OLF and 20 age-and-sex
      matched control subjects were measured with an immunonephelometric method. Plasma
      fibronectin concentrations were significantly elevated in the patients with OPLL
      or OLF, independently of associated endocrinologic abnormalities, when compared
      with the control subjects. Because fibronectin is one of the essential factors in
      endochondral ossification, it is probable that the higher fibronectin
      concentration in plasma acts as a promoter of the development of OPLL and OLF.

PMID- 8278845
TI  - Topographic differences of 1H-NMR relaxation times (T1, T2) in the normal
      intervertebral disc and its relationship to water content.
AB  - 1H-nuclear magnetic resonance studies, in vitro, on normal intervertebral discs
      dissected from adult bovine (3- or 4-year-old) coccygeal vertebrae were performed
      to clarify topographic differences in relaxation times (T1, T2) and relationships
      between the relaxation times and water content. Immediately after death,
      intervertebral discs were dissected from 1st/2nd and 2nd/3rd coccygeal vertebrae
      and divided into three specimens: the nucleus pulposus, inner anulus fibrosus,
      and outer anulus fibrosus. T1, T2, and water content were measured for the
      specimens collected from 15 intervertebral discs (untreated group). Secondly,
      specimens were similarly collected from 12 intervertebral discs and were treated
      to changed water contents (dehydrated group and hydrated group). For each treated
      specimen, T1, T2, and water content were measured. The results showed highly
      significant differences (P < 0.01) in T1 values among the nucleus pulposus, inner
      anulus fibrosus, and outer anulus fibrosus, and also in T2 values between the
      nucleus pulposus and anulus fibrosus. In each of the nucleus pulposus and anulus
      fibrosus, a positive linear relationship (r = 0.97, P < 0.01) was found between
      T1 and water content. The respective regression lines for the nucleus pulposus
      and anulus fibrosus had different slopes, and the slope of the nucleus pulposus
      was significantly greater than that of the anulus fibrosus. Thus, the decrease in
      water content shortens the T1 in intervertebral discs, and changes in water
      content have a greater influence on T1 in the nucleus pulposus than in the anulus
      fibrosus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278846
TI  - The increased signal intensity at the vertebral body endplates after
      chemonucleolysis demonstrated by magnetic resonance imaging.
AB  - Changes in signal intensity observed by magnetic resonance imaging in the
      contiguous end plates of injected discs after chemonucleolysis over a period of 2
      years in 28 patients were evaluated. These changes appeared to be of two types; a
      transiently increased signal intensity on T2-weighted images, and a progressively
      increased signal intensity on T1-weighted images with isointense or hyperintense
      signal on T2-weighted images. The former appeared within three months and
      disappeared within 2 years. This change was observed in six patients (21%), whose
      mean age was higher than that of the other patients. This change correlated with
      the preinjection state of the affected disc. The latter appeared after 2 years
      and was accompanied by sclerotic changes on roentgenograms. These changes were
      observed in five patients (18%). The discs, of which the contiguous end plates
      showed these changes, did not recover the decreased nuclear signal intensity in
      four patients. These changes are considered to be a sign of degenerative
      spondylosis in the treated segment.

PMID- 8278847
TI  - Diagnosis of subtle thoracolumbar burst fractures. A new radiographic sign.
AB  - A previously undescribed radiographic sign, the posterior vertebral body angle is
      successful in distinguishing subtle burst type fractures from compression
      fractures of the thoracolumbar spine. Correct diagnosis is imperative for proper
      treatment and accurate prognosis. When positive, this sign will alert the
      orthopaedist so that further diagnostic testing with computed tomography or
      sagittal tomograms may be performed. The sensitivity of this sign in diagnosing
      subtle burst type injuries is 75%.

PMID- 8278848
TI  - Diagnosis of lumbar arachnoiditis by myeloscopy.

PMID- 8278849
TI  - Three-dimensional spinal deformity in scoliosis associated with cerebral palsy
      and with progressive muscular dystrophy.
AB  - The authors analyzed lateral deviation, anteroposterior deformity, and rotation
      of the spinal column of 11 patients with scoliosis associated with cerebral palsy
      (CP) and 11 patients with progressive muscular dystrophy (PMD). There was a
      correlation between the magnitude of Cobb angle and that of the vertebral
      rotation in scoliosis associated with both CP and PMD, but the ratio of spinal
      rotation to Cobb angle in the former was lower than that in the latter. The
      magnitudes of thoracic kyphosis and of lumbar lordosis were not correlated with
      Cobb angle in either group, but the sagittal plane deformity in the CP patients
      was less severe than that in the PMD patients, and the latter demonstrated
      kyphosis of the lumbar spine and lordosis of the thoracic spine.

PMID- 8278850
TI  - A biomechanical definition of spinal segmental instability taking personal and
      disc level differences into account.
AB  - The biomechanical definition of spinal segmental instability has not been
      clarified sufficiently, because of the great personal and level differences in
      intervertebral disc deformation. This article proposes a new method of judging
      spinal segmental instability regardless of these differences, using lateral
      functional radiographs. The linear relationship between the disc geometry and the
      disc deformation was confirmed in the normal intervertebral discs. The degree of
      spinal segmental instability could be evaluated statistically by calculating a
      regression residual from the regression line of the normal discs. Strain
      distributions of an intervertebral disc in the sagittal plane also were
      investigated to make sure of the differences in the deformation behaviors between
      normal spines and unstable lumbar spines. Although normal lumbar spines showed
      the consistent deformation pattern, the patterns of the unstable lumbar spines
      were different.

PMID- 8278851
TI  - Torso muscle moment arms at intervertebral levels T10 through L5 from CT scans on
      eleven male and eight female subjects.
AB  - Moment arms for eight pairs of torso muscles were estimated based on data
      obtained from 19 sets of computed tomography (CT) scans. Muscle centroid
      locations of the rectus abdominis, external oblique, internal oblique,
      transversus abdominis, latissimus dorsi, psoas, quadratus lumborum, and the
      erector spinae mass were identified and digitized relative to vertebral body
      centers, which were also determined from the scans of the eight females and
      eleven males. Muscle moment arms were then calculated as the distance between the
      muscle and vertebral body centroids. The centroids for each torso muscle were
      plotted at each intervertebral level from T10-11 to L4-L5. When these sections
      were ordered in a cephalocaudad manner, the centroid-line paths, essential to the
      determination of muscle force lines-of-action, could be traced. Finally,
      anthropometric variables such as height, weight, torso depth, breadth, and age
      were regressed against the moment arm group means to develop several prediction
      equations that would determine moment arm lengths based on these anthropometric
      variables.

PMID- 8278852
TI  - Electromyographic power spectrum analysis of the paraspinal muscles. Long-term
      reliability.
AB  - As a prerequisite to the use of electromyographic power spectral analysis of the
      paraspinal muscles as a low-back pain treatment outcome measure, the long-term
      reliability of the technique was assessed. The myoelectric signals of the
      multifidus and iliocostalis lumborum muscles of healthy sedentary women were
      analyzed with regard to spectral parameters during a constant-force contraction,
      before and after a 3-month period. Results indicated that for both muscles,
      estimates of initial median frequency and amplitude had high test/retest
      reliability, but that the recovery and left-right difference parameters were not
      stable. Using a confidence interval method, test/retest variation for the fatigue
      parameter was found to be within the range of variability of potentially
      underlying metabolic processes.

PMID- 8278853
TI  - Failure characteristics of osteoporotic vertebral bodies monitored by acoustic
      emission.
AB  - The third lumbar vertebrae of nine elderly subjects (average age, 81.4 +/- 6.7
      years) graded osteoporotic and the second to fifth lumbar vertebrae of a 37-year
      old man graded as normal were used to investigate microdamage accumulation during
      quasi-static compression loading with an acoustic emission detection system.
      Mechanical parameters (apparent elastic modulus, stress, and strain) and acoustic
      emission event count rates were measured simultaneously. The normalized mean
      value of any mechanical parameters of normal group was significantly high with
      respect to that of osteoporotic group. The normalized mean value of cumulative
      acoustic emission event counts to maximum stress of the normal vertebrae was
      substantially small with respect to that of the osteoporotic vertebrae (p <
      0.0005, z-test). Postloading microradiographs displayed fracture lines adjacent
      to the end plates in six vertebrae of osteoporotic group. These results are
      consistent with the hypotheses that microdamages of osteoporotic vertebral bodies
      are generated and accumulate at lower strains than those of normal vertebrae at a
      specific site.

PMID- 8278854
TI  - Evaluation of clinical lumbar instability using the treadmill.
AB  - The physical signs of lumbar instability have not yet been clearly defined.
      Furthermore, they do not always coincide with the abnormal movement on flexion
      extension radiographs. Thus, the treadmill was used to evaluate clinical lumbar
      instability. The subjects were 82 patients with degenerative lumbar disease
      aggravated by walking or daily physical activities. The reproduction and
      provocation of low-back pain or pain in the lower extremities was examined during
      walking on a treadmill. The responses of the reproduction and provocation of the
      symptoms were divided into four grades. Fifteen cases were examined again using a
      treadmill after body casting to determine the indication for fusion surgery. As a
      result, the responses in the reproduction or provocation test using a treadmill
      manifest more dominant reflection of clinical symptoms suggesting clinical lumbar
      instability than the existence of the abnormal movement on flexion-extension
      radiographs. Reexamination after body casting was useful to determine the
      indications of fusion operations. The reproduction or provocation test using a
      treadmill was implied as a possible functional evaluation method of clinical
      lumbar instability.

PMID- 8278855
TI  - Prevention of dislodgement of Cotrel-Dubousset rods from tulip screws.
AB  - The authors report a case of posterior fusion of the lumbar spine using Cotrel
      Dubousset instrumentation in which the rods dislodged from the tulip-headed
      pedicle screws postoperatively. They recommend that, to avoid this complication,
      particular care be taken to ensure the locking washers are inserted tightly
      without cross threading and that an adequate length of rod is left protruding
      beyond the screw.

PMID- 8278856
TI  - Penetration of a screw into the thoracic aorta in anterior spinal
      instrumentation. A case report.
AB  - With recent advances in spine surgery, spinal instrumentation has allowed the
      introduction of varied new devices and techniques, expanding its potentials. Yet
      this has also led to the incidence of unexpected complications. The current
      article reports on a serious case the authors recently experienced, in which a
      screw used for the instrumentation of the thoracic vertebra penetrated the aorta.

PMID- 8278857
TI  - One-stage anterior and posterior correction of severe kyphosis of the cervical
      spine in neurofibromatosis. A case report.
AB  - A case is presented of a 29-year-old woman with neurofibromatosis, who had a 100
      degrees dystrophic kyphosis of the cervical spine and was successfully treated by
      a one-stage anterior and posterior correction. Anterior distractive and posterior
      compressive corrections were simultaneously applied keeping the posterior
      longitudinal ligament intact. The kyphosis was corrected to 42 degrees. Safety
      and better results of the one-stage correction of kyphosis is based on a concept
      of shortening the spinal canal.

PMID- 8278858
TI  - Selective en bloc resection of osteoid osteoma of the superior articular process
      of the sacral spine. A case report.
AB  - Selective en bloc resection of an osteoid osteoma from the superior articular
      process of the sacral spine was performed, sparing the facet joint. Computed
      tomography was very useful, both in making a diagnosis and in facilitating
      precise planning of the operative procedure. The paraspinal approach readily
      facilitated complete excision of the tumoral nidus with minimal surgical
      dissection.

PMID- 8278859
TI  - Ossified spinal meningioma en plaque.
AB  - Ossified spinal meningiomas alone are uncommon lesions and spinal meningiomas en
      plaque are even more. A rare case is presented of ossified meningioma en plaque
      in the midthoracic spine, which was totally removed. Characteristics of this
      tumor with reference to relatively pathognomonic neuroimagings are discussed.
      Microsurgical outcome of this type of tumor is expected to be good.

PMID- 8278860
TI  - Atlantoaxial dislocation as the presenting symptom of ankylosing spondylitis.
AB  - A 27-year-old woman presented with nontraumatic atlantoaxial dislocation that
      required a C1-C2 fusion. A comprehensive investigation initially failed to reveal
      any evidence of infectious or rheumatologic disease and she remained well for 3
      1/2 years, at which time a diagnosis of ankylosing spondylitis was established.
      There are no other similar cases reported in the medical literature. When dealing
      with a patient who has experienced a spontaneous atlantoaxial dislocation, a
      thorough assessment looking for an underlying infectious or inflammatory etiology
      is mandatory. Furthermore, the authors recommend that any patient who has
      negative investigations be followed long-term; an underlying covert inflammatory
      cause may only become evident after significant delay.

PMID- 8278861
TI  - Herniation of calcified cervical intervertebral disc causes dissociated motor
      loss in a child.
AB  - Herniation of the calcified nucleus pulposus is a rare complication of
      intervertebral disc calcification in children. Surgical intervention is rarely
      indicated in the majority of such cases. This paper reports a 12-year-old boy
      with a calcified nucleus pulposus at C7-T1 which had ruptured into the spinal
      canal, causing dissociated motor loss. Anterior discectomy and fusion were
      performed and the patient's muscle weakness markedly improved after surgery.

PMID- 8278862
TI  - Posterior fracture-dislocation of the thoracic spine without neurologic deficit.
      A case report and short literature review.
AB  - The authors present a case of posterior fracture-dislocation of the thoracic
      spine without neurologic deficit. A 63-year-old man injured by traffic accident.
      His spinal fracture-dislocation was treated conservatively because of his
      complications. At the present time, approximately 1 year after the injuries, the
      patient does not have any neurologic complaint. Conservative treatment should be
      adopted as the first choice in patients at older ages and in those with
      underlying diseases or serious complications.

PMID- 8278863
TI  - Traumatic lumbar disc herniation. A case report.

PMID- 8278864
TI  - Aseptic spondylodiscitis: a complication of chemonucleolysis? A case report.
AB  - Discitis after intradiscal injection of chymodiactin is nearly always associated
      with an infection introduced by the needle tip. The authors report a patient with
      a postchemonucleolysis spondylodiscitis who recovered complete without surgery or
      antibiotics. The clinical findings and results of CRP and MRI suggested an
      aseptic spondylodiscitis due to chymodiactin.

PMID- 8278865
TI  - Thoracic kyphosis associated with a thymic cyst.
AB  - Cystic masses of the thymus are usually asymptomatic. Any symptoms are usually
      related to fluid accumulation and the cyst's accompanying increase in size. The
      authors report a case presenting with kyphosis and late recognition of the
      associated thymic cyst. We found no reports in the literature of a thymic cyst
      preceded by or associated with kyphosis and the mechanisms of this association
      are unknown.

PMID- 8278866
TI  - PRIDE model methods.

PMID- 8278867
TI  - Junctional burst fractures.

PMID- 8278868
TI  - Spinal stenosis in ankylosing hyperostosis.

PMID- 8278869
TI  - Spinal stenosis in ankylosing hyperostosis.

PMID- 8278870
TI  - [Attitude to mammography screening: results of a survey of female patients].

PMID- 8278871
TI  - [3-dimensional imaging of aortic aneurysms using spiral computed tomography].

PMID- 8278872
TI  - [Ultrasonography in the postoperative monitoring of laparoscopic
      cholecystectomy].

PMID- 8278873
TI  - [Sonographic aspects of pathologic changes in the wrist and hand].

PMID- 8278874
TI  - [The legal position of the expert witness according to the X-ray Ordinance].

PMID- 8278875
TI  - [Reevaluation of impotence following TURP].
AB  - Impotence following transurethral prostatectomy is one of the main complications
      that still has a controversial origin. Many authors, reporting their experience,
      have demonstrated that this complication is due both to psychological problems
      and to organic causes. We review retrospectively 68 patients submitted to TURP.
      All patients (53 to 65 years old) were asked about their sexual efficiency before
      and after TURP, 6-12 months after surgery. Those who complained of erectile
      failure have been studied using this diagnostic protocol: plasmatic dosage of
      FSH, LH, Testosterone and Prolactin; penile Doppler ultrasound, polysomnographic
      recording of nocturnal tumescence test (NPT Test); angiography of the pudenda
      arteries has been performed in only one patient with pathological penile Doppler
      ultrasound (IPP < 0.7). The examinations demonstrated an organic impotence not
      secondary to vascular damage in 10 patients following surgery (incidence 15.6%).
      Our high incidence of this complication is, according to us, significant even if
      it should be considered in excess since in our study we used anamnestic criteria
      alone in the evaluation of sexual efficiency before surgery. In 1984 T. Lue
      demonstrated, through accurate histological preparations, that cavernous nerves
      run contiguously to the prostatic capsule at 5 and 7 hours in correspondence of
      the glandular apex. He suggested that impotence following TURP is due to
      iatrogenic lesions of these nervous structures during endoscopic resection.
      Similarly, we have conducted an anatomopathological study on prostate specimens
      taken from autopsies. We demonstrated the presence of nervous structure
      contiguously to the prostatic capsule in correspondence with the glandular apex.
      Thus, impotence following TURP probably occurs after an iatrogenic heat lesion of
      the periprostatic plexus caused by resection.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278876
TI  - [Complications of intracavernous pharmacologic infusion in impotence. Long-term
      results].
AB  - The large scale employment in recent years of vasoactive drugs in the treatment
      of impotence forms the basis for a significant statistical study on incidence of
      complications and collateral effects. We studied 658 patients submitted to ICF
      (intracavernous pharmacoinfusion) diagnostic and therapeutic in the last 6 years
      (1986-1992). The patients have been shared groups according to the period and the
      treatment: in 226 cases we have utilized papaverine, in 224 cases phentolamine
      papaverine association and in 208 cases prostaglandin E1. In the last group the
      complications have been lower: echymosis and haematoma 0.5%, priapism 1.5%,
      intracavernous fibrosis 1%, fibrotic knots 0.5%. In conclusion we confirm the
      validity of treatment with PGE1 intracavernous infusion.

PMID- 8278877
TI  - [Adjuvant chemotherapy in infiltrating bladder carcinoma. Long-term results].
AB  - The authors present the long-term of adjuvant chemotherapy using M-VEC scheme
      (Mtx 20 mg/mq; vinblastine 0.1 mg/kg; CDDP 40 mg/mq; epirubicin 30 mg/mq each 21
      day for six cycles) effected in 28 patients (21 males and 7 women with average
      age of 67) undergone radical cystectomy for invasive bladder carcinoma p G2-3 T-4
      N + M0. Total survival after 5 years was 28.6% while disease-free survival is
      18.8%; in 71.3% there are been clinical progression and the mortality to 5 years
      was 62%.

PMID- 8278878
TI  - [Prophylaxis of transitional cell carcinoma of the bladder G1-G2; pTa-pT1 with
      mitomycin C or interferon alpha-2a. Preliminary data].
AB  - No. 54 patients with transitional cell carcinoma G1-2; pTa-pT1, were treated with
      intravesical therapy with Mitomycin C (MMC) (first group of 27 patients), and
      Interferon alfa 2a (IFN) (second group of 27 patients), following transurethral
      resection. The objective of this trial was to compare the prophylactic activity
      of these two drugs. All patients were evaluated with cystoscopy and urine
      cytology. Mean follow-up was for the first group of patients (MMC) of 10.4
      months, for the second group (IFN) of 12 months. The incidence of recurrence in
      the first group (MMC) was 11.1% with a recurrence rate of 2.1. In the second
      group (IFN) the incidence of recurrence was 51.9% with a recurrence rate of 7.4.
      No case of progression evaluated by grade and stage was observed. The side
      effects were more frequent in the MMC group and they were mainly due to
      chemocystitis. These data suggest that MMC appears to be superior to IFN in
      intravesical therapy of superficial bladder carcinoma.

PMID- 8278879
TI  - [The use of hemorrhage occluder pins in radical pelvic urologic surgery].
AB  - The authors present the use of "Hemorrhage Occluder Pins" in pelvic urologic
      radical surgery, as a means of hemostasis for the retropubic venous plexus. The
      application technique and the bio-technological characteristics of the occluder
      pin are discussed.

PMID- 8278880
TI  - [Full-term pregnancy in a patient with chronic renal failure undergoing long-term
      dialysis: 12 years. Clinico-therapeutic and psycho-nephrologic considerations].

PMID- 8278881
TI  - [Percutaneous transluminal angioplasty in the treatment of stenosis of the renal
      artery in solitary functioning kidney].
AB  - The authors report 2 cases of patients with single functioning kidney and severe
      hypertension caused by renal artery stenosis who were treated by percutaneous
      transluminal angioplasty (PTA). In one case an early and persistent improvement
      of renal function and a reduction of pressure values were observed. In the other
      patient, with preexistent severe functional damage, a progressive impairment of
      renal function required haemodialysis. On the basis of these results and of other
      reports in the literature, PTA is proposed as elective treatment of renal artery
      stenosis in patients with single functioning kidney.

PMID- 8278882
TI  - [Renal angiomyolipoma and oncocytoma: sensitivity, diagnosis, and controversy
      regarding CT and MR].
AB  - We have studied the accuracy of CT and MR in 9 oncocytoma and 6 angiomyolipoma,
      observed in our department from 1985 to 1991. The radiographic patterns of
      angiomyolipoma are due to the presence of fat in the tumors: on the CT
      angiomyolipoma appeared as low-density lesions (negative Hounsfield units) with
      an area of intermixed tissue density which represented myomatous and
      angiomyomatous elements. The infusion of contrast medium increased the difference
      between neoplasm and parenchyma because of the scarce enhancement of the
      angiomyolipoma. MR imaging of angiomyolipoma exhibited areas of high intensity
      signals on both T1 and T2 weighted images. The infusion of Gadolinium (1 mmol/kg)
      decreased the difference of signal intensity between angiomyolipoma and
      parenchyma so that the lesions appeared less clear. As far as oncocytoma
      diagnosis is concerned, neither CT nor MR appeared less clear. As far as
      oncocytoma diagnosis is concerned, neither CT nor MR appeared accurate and no
      specific pattern was identified. The "central stellate scar" was shown on CT in
      only 1 oncocytoma 7 cm large.

PMID- 8278883
TI  - [Contraceptive methods].

PMID- 8278885
TI  - [Contraception by intrauterine device].

PMID- 8278884
TI  - [The Billings method].

PMID- 8278886
TI  - [Diffusing clear and practical information on contraception has never been
      simple].

PMID- 8278887
TI  - [Oral contraception].

PMID- 8278888
TI  - [Contraception in 1993].

PMID- 8278889
TI  - [Contraception and drugs].

PMID- 8278890
TI  - [Oral contraception: users' questions].

PMID- 8278891
TI  - [A family planning center: role of the nurse].

PMID- 8278892
TI  - [Conjugal counseling and contraception].

PMID- 8278893
TI  - [Voluntary sterilization].

PMID- 8278894
TI  - [History of contraception in France].

PMID- 8278895
TI  - Evaluation of 5-[18F]fluoropropylepidepride as a potential PET radioligand for
      imaging dopamine D2 receptors.
AB  - This study evaluated the utility of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3
      [18F]fluoropropyl)-2,3 - dimethoxybenzamide ([18F]fluorpropylepidepride), [18F]5
      FPrEpid, as a ligand for PET studies of cerebral dopamine D2 receptors. The in
      vitro affinity for the rat striatal dopamine D2 receptor, KD 138 pM, was
      determined by Scatchard analysis of in vitro binding to rat striatal homogenate.
      The apparent lipophilicity, log kw 1.6, was measured with reverse phase HPLC at
      pH 7.5. The receptor specificity was determined by competitive displacement of
      [18F]5-FPrEpid by a variety of neurotransmitter ligands. Only dopamine D2 ligands
      displaced [18F]5-FPrEpid with high affinity. Positron tomographic imaging studies
      in primates of [18F]5-FPrEpid demonstrated a stable striatal uptake of 0.02%
      injected dose/ml for up to 5 h after injection. The striatal: cerebellar ratio
      increased from 2 at 15 min, to 7 at 200 min, and to 10 at 300 min. Striatal
      uptake was displaceable by haloperidol (1 mg/kg) or raclopride (2.5 mg/kg) to
      cerebellar levels with a t1/2 of washout of 9 or 15 min. Striatal uptake was
      mildly susceptible to displacement by d-amphetamine (1-2 mg/kg) released
      endogenous dopamine; d-amphetamine administration produced a 10% h increase in
      the rate of striatal washout. Although uptake in the striatum is reversible, an
      equilibrium between receptor bound [18F]5-FPrEpid in striatum and [18F]5-FPrEpid
      in plasma is not reached within 5 h postinjection.

PMID- 8278896
TI  - Failure of the three compartment model to describe the pharmacokinetics in brain
      of a high affinity substituted benzamide.
AB  - The applicability of using the standard 3-compartment model to describe the
      neuropharmacokinetics of a high affinity substituted benzamide was investigated.
      We performed the following experiments using the [18F]-5-(3-fluoropropyl) analog
      of epidepride ([18F]5-FPrEpid), a potent dopamine D2 receptor antagonist:
      constant left ventricular infusion, first-pass clearance, varying ligand specific
      activity, and displacing bound ligand with varying amounts of unlabelled ligand.
      Taken together, the information from these experiments rigorously tests the
      standard 3-compartment model. The obtained data and predictions from the model of
      the kinetic behavior of the ligand are inconsistent. The measured and model
      predicted dissociation rate (measured koff = 0.065 min-1, model prediction koff =
      0.007 min-1) and the equilibrium dissociation constant (measured KD = 0.14 nM,
      model prediction KD = 2.2 nM) differ by an order of magnitude. Furthermore, the
      model cannot be used to accurately estimate the receptor density. We postulate
      that the synapse geometry and physical relationship between receptors are
      necessary components of a model that describes the pharmacokinetics of [18F]5
      FPrEpid.

PMID- 8278897
TI  - Prenatal methamphetamine attenuates serotonin mediated renin secretion in male
      and female rat progeny: evidence for selective long-term dysfunction of serotonin
      pathways in brain.
AB  - In adult rats, methamphetamine produces biochemical alterations in brain
      serotonin (5-HT) neurons. Since 5-HT is critical to the development of fetal 5-HT
      neurons and target tissues, we hypothesized that in utero exposure to
      methamphetamine could result in long-term alterations in postnatal 5-HT systems.
      Pregnant Sprague-Dawley rats, administered either saline or (+/-)methamphetamine
      (5 mg/kg, s.c., b.i.d.) from gestational day 13 to 20, were divided into three
      treatment groups: Saline-injected/Ad Lib Fed (VEH); Saline-injected/Pair Fed
      (PF); and methamphetamine injected (METH). Prenatal methamphetamine exposure did
      not alter litter size, gender number, or progeny birth weights. Functional
      alterations in serotonergic systems were determined in postnatal day (PD) 70 male
      progeny and in PD 30 female progeny by measuring changes in 5-HT mediated
      increases in plasma hormones following a single injection of the 5-HT releaser p
      chloroamphetamine (PCA; 8 mg/kg). Prenatal methamphetamine produced long-term
      marked (-30 to -62%) attenuation of plasma renin responses to PCA in male and
      female progeny. In contrast, no alterations were observed in the ACTH,
      corticosterone, or prolactin responses to PCA in male and female progeny.
      Prenatal methamphetamine did not alter basal levels of any hormones measured
      regardless of gender. No significant differences were observed in the density of
      cortical or hypothalamic 5-HT uptake sites, or in the density of cortical 5-HT1
      or 5-HT2 receptors in male progeny. The lack of significant differences in
      cortical 5-HT uptake sites observed between PF and METH treated dams 2 days post
      parturition indicates that methamphetamine was not neurotoxic to the pregnant
      dams. These data, which demonstrate longterm postnatal deficits in 5-HT mediated
      renin secretion, suggest selective functional alterations of brain 5-HT systems
      in male and female progeny exposed in utero to methamphetamine.

PMID- 8278898
TI  - Kainic acid seizures cause enhanced expression of cholecystokinin-octapeptide in
      the cortex and hippocampus of the rat.
AB  - Immunocytochemistry and in situ hybridization techniques were used for
      investigating changes in cholecystokinin immunoreactivity and mRNA in the
      cerebral cortex and hippocampus after kainic acid-induced limbic seizures in the
      rat. Marked increases in cholecystokinin mRNA concentrations were observed in
      layers II/III and V/VI of the cerebral cortex, in CA1 pyramidal neurons of the
      hippocampus, and in presumptive basket cells of the dentate gyrus 1 and 2 days
      after the acute seizures. Whereas cholecystokinin mRNA contents returned to
      normal in the cerebral cortex and the CA1 sector at later intervals, high
      concentrations were observed in basket cells even 2 months after the initial
      seizures. Accordingly, cholecystokinin-like immunoreactivity was intensified in
      the cerebral cortex, CA1 sector and in presumed basket cells of the hippocampus
      30 days after kainic acid. Besides its high content in basket cells,
      cholecystokinin-like immunoreactivity was primarily present in neuronal fibers or
      diffusely distributed in the respective brain area. In the hippocampus, strongly
      enhanced staining for cholecystokinin was also observed in the alveus, the
      stratum lacunosum moleculare, and in the inner molecular layer, suggesting
      increased concentrations of the peptide in afferent and efferent fibers of the
      hippocampus. The present experiments suggest a strong activation of
      cholecystokinin systems in the brain after kainic acid-induced limbic seizures in
      the rat. This is indicated by pronounced increases in cholecystokinin mRNA in the
      cortex and individual cell types of the hippocampus (basket cells, granule cells,
      and CA1 pyramidal neurons). The subsequent increases in cholecystokin
      immunoreactivity even surpass those in mRNA. The observed changes may be part of
      the self-defense mechanisms that protect the animals during subsequent epileptic
      episodes.

PMID- 8278899
TI  - GABAB-receptor activation alters the firing pattern of dopamine neurons in the
      rat substantia nigra.
AB  - Previous electrophysiological experiments have emphasized the importance of the
      firing pattern for the functioning of midbrain dopamine (DA) neurons. In this
      regard, excitatory amino acid receptors appear to constitute an important
      modulatory control mechanism. In the present study, extracellular recording
      techniques were used to investigate the significance of GABAB-receptor activation
      for the firing properties of DA neurons in the substantia nigra (SN) in the rat.
      Intravenous administration of the GABAB-receptor agonist baclofen (1-16 mg/kg)
      was associated with a dose-dependent regularization of the firing pattern,
      concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the
      firing rate of the DA neurons was dose-dependently decreased. Also,
      microiontophoretic application of baclofen regularized the firing pattern of
      nigral DA neurons, including a reduction of burst firing. Both the regularization
      of the firing pattern and inhibition of firing rate produced by systemic baclofen
      administration was antagonized by the GABAB-receptor antagonist CGP 35348 (200
      mg/kg, i.v.). The GABAA-receptor agonist muscimol produced effects on the firing
      properties of DA neurons that were opposite to those observed following baclofen,
      i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA
      receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose
      dependent increase in the firing rate of the nigral DA neurons as well as a
      slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3
      10 min) did neither promote nor prevent the regularization of the firing pattern
      or inhibition of firing rate on the nigral DA neurons produced by baclofen. The
      present results clearly show that GABAB-receptors can alter the firing pattern of
      nigral DA neurons, hereby counterbalancing the previously described ability of
      glutamate to induce burst firing activity on these neurons.

PMID- 8278900
TI  - Changes in calpain and brain spectrin immunoreactivity accompany sprouting in the
      deafferented hippocampus.

PMID- 8278901
TI  - Comparison of two PET radioligands for imaging extrastriatal dopamine receptors
      in the human brain.

PMID- 8278902
TI  - [Luxembourg--nurses' hierarchy. Interview by Mette Fjordbo].

PMID- 8278903
TI  - [Luxembourg--voluntary unpaid work. Interview by Mette Fjordbo].

PMID- 8278904
TI  - [Luxembourg--gratuities for nurses].

PMID- 8278905
TI  - [EEC: the Danish system close to acceptance].

PMID- 8278906
TI  - [Laxatives--nursing staff's easy solution].

PMID- 8278907
TI  - [Research: back to Virginia. Interview by Grethe Kjaergaard].

PMID- 8278908
TI  - [Psychotherapy--dying can be beautiful].

PMID- 8278910
TI  - [Negotiations 93. Testing one's determination].

PMID- 8278909
TI  - [Having the right to rehabilitation].

PMID- 8278911
TI  - [Luxembourg--Nurses in the EEC. A European cocktail].

PMID- 8278912
TI  - [Negotiations 93--increasing pressure and expectations].

PMID- 8278913
TI  - [Emergency room--outpost where nobody can make plans].

PMID- 8278914
TI  - [Emergency room--a daring tale about the awful. Interview by Mette-Marie
      Davidsen].

PMID- 8278915
TI  - [Emergency room--a major accident. Interview by Anne Vesterdal].

PMID- 8278916
TI  - [Hospital: County Council gave all power to medical directors].

PMID- 8278917
TI  - [Anniversary: a quarter-century struggle].

PMID- 8278918
TI  - [Anniversary: a lovely day for Kirsten].

PMID- 8278919
TI  - [Patient insurance--a plaster on the wound. Interview by Kirsten Bjornsson].

PMID- 8278920
TI  - [Near death experience--dying is a momentous part of living. Interview by Lars
      Peter Bergqvist].

PMID- 8278921
TI  - [Nursing story: a place where the sky meets the sea].

PMID- 8278922
TI  - [Health nursing--understanding and methods].

PMID- 8278923
TI  - [Amnesty--released but forbidden regular employment. Interview by Lars Peter
      Bergqvist].

PMID- 8278925
TI  - [Negotiations 93--movement].

PMID- 8278924
TI  - [Asthma school--getting new inspiration in the snow].

PMID- 8278926
TI  - [Chernobyl--from a forgotten hospital].

PMID- 8278927
TI  - [Chernobyl--7 years after].

PMID- 8278928
TI  - Toxicokinetics and structure-activity relationships of nine para-substituted
      phenols in rat embryos in vitro.
AB  - The purpose of this study was to examine the toxicokinetics of embryo uptake
      following exposure to a variety of chemically related phenols in rat embryo
      culture. The uptake of nine radiolabeled para-substituted phenols by day 10 (9-13
      somite stage) rat embryos in vitro was determined from 1 to 42 hrs after being
      placed in culture media containing various phenols. Uptake was rapid, having a
      half-life of 3 hr or less, with 7 of the nine compounds having uptake half-times
      of less than one hour. The equilibrium concentration in the embryo ranged from 53
      to 136% of the media concentration, indicating only a factor of 2 in maximum
      discrimination against the compound for any of the phenols studied. The fraction
      of radioactivity remaining unbound in the media decreased with increasing log P
      (octanol/water partition coefficient). The binding was calculated to be 50% for
      log P = 1.77 from the fitted regression equation and decreased by a factor of 5.9
      for every decade increase in P. When hepatocytes were also present in the media
      the equilibrium concentration in the embryos was less than when hepatocytes were
      absent. With the limited data, four of the phenols appeared to have no (i.e.,
      zero) equilibrium level when hepatocytes were present. Thus the metabolites
      produced by the hepatocytes appeared to have less affinity for the embryo than
      the parent phenol. Toxicodynamic information as given by the effective
      concentration of the phenol in the embryo to cause somite or tail teratological
      effects was best predicted by the measured unbound fraction.

PMID- 8278929
TI  - Strain-dependent effect of ethanol on ventricular septal defect frequency in
      White Leghorn chick embryos.
AB  - We have tested the potential of a single dose of ethanol (0.20 ml 50% ethanol in
      chick Ringer's saline (CRS) administered into the air sac) to produce ventricular
      septal defect (VSD) in three distinct commercially available strains of White
      Leghorn chick embryo: stress-resistant Dekalb Delta strain, Hy-Vac SPF type V,
      and Hy-Vac SPF type L. Eggs were controlled for both size and developmental stage
      (Hamburger-Hamilton stage 18-19) at time of injection. The frequency of VSD in
      Dekalb Delta embryos was 4.0% (1/25), in Hy-Vac SPF type L embryos 9.1% (3/33),
      and in Hy-Vac SPF type V embryos 38.9% (14/36). Statistical analysis with the two
      tailed Fisher Exact Test indicated that frequencies were not significantly
      different (P = 0.3215) when Dekalb Delta and Hy-Vac type L embryos were compared.
      However, the frequency of VSD for Hy-Vac type V embryos was significantly greater
      than that for either the Dekalb Delta or the Hy-Vac type L embryos (P < 0.005).
      All VSDs observed were located within the crista supraventricularis. When Hy-Vac
      SPF type V embryos were exposed to either 0.20 ml 50% ethanol in CRS or to 0.20
      ml CRS (controls), ethanol-treated embryos showed a VSD incidence of 34.1%
      compared with a 3.6% incidence in the controls (P = 0.0017). These data suggest
      that ethanol is the cause of VSD in this strain. From the results of this study,
      we are led to conclude that different commercial strains of White Leghorn chick
      embryo show different susceptibilities to the induction of VSD by ethanol.

PMID- 8278930
TI  - Developmental changes in the optic nerve related to ethanol consumption in
      pregnant rats: analysis of the ethanol-exposed optic nerve.
AB  - Visual impairment is one of the most common ophthalmic abnormalities in fetal
      alcohol syndrome. Pathologic changes in optic nerve development related to
      alcohol consumption could be involved in this dysfunction. In order to assess the
      consequences of pre- and postnatal exposure to alcohol on the developing optic
      nerve, we administered an ethanol-containing liquid diet (5% w/v) before and
      during gestation and throughout lactation to rats and their offspring. A group of
      control animals were kept on a pair-fed isocaloric diet. The optic nerves were
      obtained at key stages from fetuses (21 days of gestation) and pups (4, 7, 14, 21
      and 28 postnatal days). Samples of the optic nerve cross-section, behind the
      eyeball, were processed for analysis of gliogenesis, myelinogenesis, axonal
      growth, and remodelling events, using light and electron microscopy. Qualitative,
      morphometric, and immunocytochemical analyses, alternatively using anti-GFAP and
      anti-MBP antibodies, were carried out. Optic nerve cross-sections from prenatal
      and postnatal alcohol-exposed rats showed a decrease in size. Ultrastructural
      alterations and retarded development in macroglial cells, optic axons, and myelin
      sheath were also observed. The most prominent abnormalities were: damage of
      cytoplasmic organelles and disorganization of cytoskeleton in astrocytes; a
      decrease in free ribosome density and nuclear membrane inclusions in
      oligodendrocytes; and fragmentation of lamellae, aberrant myelin sheaths and
      intralamellar inclusions in myelin. These findings suggest that alcohol abuse
      during pregnancy is teratogenic to the optic nerve and closely related to the
      altered visual function.

PMID- 8278931
TI  - A morphological and family study on isolated terminal transverse type of
      congenital limb deficiency in Hungary, 1975-1984.
AB  - A population-based and validated data set of 195 cases with isolated terminal
      transverse-type congenital limb deficiency was evaluated in Hungary, 1975-1984.
      Terminal transverse types of congenital limb deficiency are not usually
      associated with non-limb defects, and typically only one limb is affected. Upper
      limb is more frequently affected than lower (9:1) in monomelic cases. The left
      side and females are affected more often in upper limbs while lower limb defects
      are evenly distributed between right and left sides and both sexes. Familial
      occurrence was not found.

PMID- 8278932
TI  - New method for the detection of cardiovascular malformations in rat fetuses:
      gelatin-embedding-slice method.

PMID- 8278933
TI  - Cadmium-induced inhibition of proliferation and differentiation of embryonal
      carcinoma cells and mechanistic aspects of protection by zinc.
AB  - Murine embryonal carcinoma cells have been used in in vitro models to study the
      effects of cadmium chloride on proliferation and differentiation of early
      embryonic cells. This approach allows the various cell types within the early
      embryo as well as several developmental mechanisms to be dissected and studied in
      isolation using larger numbers of cells than would be readily available from the
      embryo itself. The present study shows that both embryonal carcinoma cell
      proliferation and differentiation into parietal endoderm are inhibited by cadmium
      chloride. The effects are counteracted by the additional presence of zinc
      chloride. The uptake of cadmium into the cells is inhibited in the presence of
      zinc chloride, suggesting that competition between these metals for passage into
      the cells contributes to the mechanism underlying the protective effect of zinc.
      In addition, metallothionein gene expression is enhanced more rapidly after
      simultaneous incubation with zinc chloride, indicating that the attenuating
      effect of zinc on cadmium toxicity is also partly attributable to detoxification
      by metallothioneins.

PMID- 8278934
TI  - Real time micro-fiberoptic monitoring of endogenous fluorescence in the rat
      conceptus during hypoxia.
AB  - A micro-fiberoptic methodology has been developed for non-invasive, real time
      measurement of endogenous pyridine nucleotide fluorescence from the surface of
      the visceral yolk sac (VYS) in intact, viable rat conceptuses. Gestational day
      (GD) 10-12 conceptuses are maintained in a customized perifusion system, which
      allows for control of oxygenation, as well as the continuous measurement of pH
      and oxygen concentration in the effluent perifusate. Miniaturized light guides
      were constructed by drawing 250 microns ESKA acrylic optical fibers through a
      stainless steel sheath with a high strength epoxy polymer. A single fiber
      supplied the excitation signal from a mercury arc lamp at a wavelength of 366 nm.
      The emission signal was returned via three additional fibers, electronically
      amplified, processed, and recorded, using a dual channel lamp-compensated
      fluorometer, optimized for detection of reduced pyridine nucleotides at 455 nm.
      Endogenous fluorescence in the conceptus was monitored by placing the polished
      tip of the sensor directly on the surface of the VYS. Oxygen-equilibrated
      conceptuses, exposed to 100% nitrogen, produced a reproducible biphasic surface
      fluorescence peak, which returned to baseline levels upon reoxygenation of the
      perifusate. This biphasic response consisted of an initial rapid rise in
      fluorescence (phase I), followed by an attenuated rate in fluorescence signal
      increase (phase II). The hypoxia produced age-dependent rates of fluorescence
      change during phase I, while phase II remained relatively unchanged throughout GD
      10-12. These results demonstrate the ability to monitor endogenous fluorescence,
      non-invasively and in real time, during the period of organogenesis in the intact
      rat conceptus and will provide valuable information in studies of embryonic
      metabolism and response to chemical embryotoxicants.

PMID- 8278935
TI  - Effects of developmental stage and tissue type on embryo/fetal DNA distributions
      and 5-fluorouracil-induced cell-cycle perturbations.
AB  - Cell-cycle analysis of nuclei obtained from the circulating erythroblasts
      (gestational day [GD] 11-16), livers (GD 14-19), and whole embryos (GD 10-13) or
      remaining (extrahepatic) tissues (GD 14-16) of rat embryos/fetuses revealed age-
      and tissue-dependent variations in the relative percentages of cells in the
      G0/G1, S, and G2/M phases of the cell cycle. With development, the rate of cell
      proliferation declined resulting in decreases in the relative percentage of S
      phase cells and increases in the G0/G1 percentage, while the percentage of G2/M
      phase cells remained relatively constant. Comparing tissue cell-cycle profiles
      during development, erythroblasts exhibited the most rapid age-dependent decline
      in S-phase percentage (from 75% at GD 11 to 8% by GD 14), embryos/extrahepatic
      tissues exhibited a more gradual reduction (from 55% at GD 10 to 14% by GD 15),
      while the hepatic isolates exhibited a relatively constant S-phase percentage of
      approximately 40% from GD 14 to GD 18 before decreasing to 23% at GD 19. These
      age-dependent variations suggest that cell-cycle distribution may be useful in
      staging embryogenesis and in detecting abnormal development. To determine how
      these developmental and organ-specific cell-cycle variations affect toxic
      response, we sampled GD 11-13 embryos 6 hr after maternal administration of a
      teratogenic dose of 5-fluorouracil (5-FU), a thymidylate synthetase inhibitor
      that induces S-phase accumulation. The results indicate that, on a relative
      basis, the amount of induced S-phase accumulation in erythroblasts and whole
      embryos 6 hr postdosing increased with development.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8278936
TI  - Developmental toxicity of gemcitabine, an antimetabolite oncolytic, administered
      during gestation to CD-1 mice.
AB  - Gemcitabine was given intravenously to female mice on gestation days (GD) 6-15 at
      doses of 0, 0.05, 0.25, or 1.5 mg/kg/day (0, 0.15, 0.75, or 4.5 mg/m2/day,
      respectively). Animals assigned to the teratology segment (25/group) were killed
      on GD 18 for examination of maternal hematologic parameters and organ weights, as
      well as fetal viability, weights, and morphology. The postnatal segment females
      (20/group) were allowed to deliver, and offspring physical, behavioral, and
      reproductive parameters were monitored. After offspring weaning, these dams were
      killed for hematologic and organ weight evaluations. At necropsy, 3 days after
      the final dose, the teratology segment dams showed dose-related increases in
      spleen and thymus weights. These changes were accompanied by a dose-related
      decrease in leukocytes and modest increases in mean corpuscular volume (MCV) and
      hemoglobin (MCH) at the two higher doses. On postpartum day (PPD) 21, the dams in
      the postnatal segment showed no treatment-related effects on these organ weights
      or hematologic parameters, indicating recovery of these maternal parameters
      within 3.5 weeks following termination of treatment. The decreases in maternal
      body weight and food consumption observed during gestation, and in liver and
      uterine weights at term in the 1.5 mg/kg/day group, were considered to be
      secondary to a high rate of prenatal mortality, evidenced by increased
      resorptions in the teratology segment and decreased live litter size in both
      segments of the study. Additional indications of developmental toxicity in this
      dose group were an increased incidence of malformations, primarily cleft palate,
      decreased fetal weights in the teratology segment, and decreased neonatal
      survival in the postnatal segment.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8278937
TI  - Tail short variable: characterization of a new mouse mutant, and its possible
      analogy to certain human vascular disruption defects.
AB  - A new mouse mutant, tail short variable (Tsv) produces a reduction deformity of
      the tail, growth retardation, and, in adults, a mild anemia. Genetic and
      embryological studies show that on all genetic backgrounds there is variable
      viability of Tsv/Tsv and Tsv/+ and phenotypic overlap within these and with +/+.
      A modifier is located to a short segment of chromosome 7, which alters the tail
      length of Tsv/+ mice up to 15%. The modifier, Tsv, and a coat texture mutant come
      from the same wild Peru mouse. The tail deformity is associated with, and may be
      caused by, a vascular disruption of the caudal aorta starting on day 11 of
      gestation. Thus Tsv appears to be different from each of the thirty known mouse
      mutants involving the tail. It is suggested that Tsv could be a mouse model for
      human conditions involving transverse terminal limb defects such as Moebius and
      de Lange syndromes.

PMID- 8278938
TI  - Observations with high-dose Mydocalm therapy.
AB  - The effect of coated Mydocalm tablet, given in 3 x 150-mg daily doses for 3 weeks
      to 47 patients, simultaneously with physiotherapy, has been examined in
      comparison to the results of 47 patients treated with physiotherapy solely. In
      the group of patients receiving Mydocalm as an adjuvant to physiotherapy the
      alleviation of pain and moderation of muscular hypertonia and spasm were observed
      within a shorter period. On the basis of the results of these examinations the
      use of Mydocalm is recommended as an adjuvant to complex therapy, in 300-450-mg
      daily doses, for the treatment of locomotor diseases accompanied by muscular
      hypertonia, muscular spasticity, and contracture.

PMID- 8278939
TI  - Effect of tensiomin in ischaemic dilatative cardiomyopathy.
AB  - The effect of the angiotensin-converting enzyme inhibitor, Tensiomin, has been
      examined in patients suffering from ischaemic dilatative cardiomyopathy who had
      become unresponsive to combined vasodilatator--diuretic--digitalis therapy. The
      results were evaluated according to the changes in NYHA classes and
      echocardiographic parameters. Significant improvement was observed in response to
      Tensiomin in 38 of the 52 patients (73%). On the basis of the results the use of
      captopril (Tensiomin) is highly recommended for the treatment of ischaemic
      dilatative cardiomyopathy.

PMID- 8278940
TI  - Double-blind comparative examination of ketoconazole 1% cream and clotrimazole 2%
      ointment in superficial dermatomycosis.
AB  - Comparative examinations were performed with ketoconazole (Nizoral) 1% cream and
      clotrimazole (Canesten) 2% ointment in 41 patients suffering from superficial
      dermatomycosis. Twenty-one patients were treated with ketoconazole, twenty
      patients, with clotrimazole twice daily, for a maximum 4 weeks. The results of
      the clinical and mycological examinations showed no significant differences when
      comparing the two groups treated with the different products. Trichophyton rubrum
      was the most frequently isolated strain in both groups. Side-effect occurred in
      two of the patients treated with ketoconazole cream (erythema, burning sensation)
      which did not require the discontinuation of therapy. In the clotrimazole-treated
      group the therapy had to be discontinued in 3 patients because of dryness of
      skin, burning sensation, and aggravation of inflammatory symptoms.

PMID- 8278941
TI  - Changes in lipid, peroxide, and anti-oxidant blood levels during piroxicam
      (Hotemin) treatment.
AB  - The authors examined the lipid-peroxide (malondialdehyde) blood concentration of
      patients suffering from rheumatoid arthritis of osteoarthrosis. Of the anti
      oxidant compounds, they examined the vitamin E concentration of blood plasma and
      catalase as well as glutathione-peroxidase enzyme activities. They also measured
      the oxidation capacity of blood plasma. It has been observed that the functional
      condition of patients in both disease groups improved following a 14-day
      treatment (20 md/day Hotemin). The degree of lipid-peroxidation (malondialdehyde
      content) as well as plasma oxidation capacity decreased in patients with
      osteoarthrosis, while these values did not change in patients suffering from
      rheumatoid arthritis. When examining the anti-oxidant enzymes in rheumatoid
      arthritis, a significant change was observed in glutathione-peroxidase activity.
      On the basis of the results it may be concluded that piroxicam has no direct anti
      inflammatory action, but as an anti-oxidant, it exerts an action which is disease
      specific.

PMID- 8278943
TI  - Jeno Jendrassik and the beginnings of experimental physiology in Hungary.

PMID- 8278942
TI  - The role of nitroglycerin preparations in the treatment of post-acute and chronic
      pancreatitis.
AB  - The role of nitrate compounds in the therapy of pancreatic diseases is discussed
      in this review. A short overview is given about the physiological background of
      the treatment: the regulation of Oddi's sphincter function and its pharmacology.
      An adjuvant role is attributed to the free outflow of pancreatic secretion in the
      treatment of pancreatic pain and in the prevention of relapses. The authors
      describe their clinical practice during the last 15 years: nitrates with short
      half-life in the treatment of acute pancreatitis (amylnitrit or nitroglycerin
      spray) which have a low risk of developing nitrate tolerance; chronic
      administration of retard nitroglycerin in chronic pancreatitis and Oddi's
      sphincter hypertonic dyskinesia. For preventing the induction of nitrate
      tolerance, Nitromint retard is recommended twice a day combined with a calcium
      antagonist or with theophylline during the nitrate-free period.

PMID- 8278944
TI  - [Music and chaos, Paracelsus and Morgan Kane].

PMID- 8278945
TI  - [The 1993 Nobel Prize in physiology and medicine--split genes].

PMID- 8278946
TI  - [The 1993 Nobel Prize in chemistry--polymerase chain reaction and directed
      mutagenesis].

PMID- 8278947
TI  - [Which of the health services we offer are effective?].

PMID- 8278948
TI  - [Skiing injuries and safety].

PMID- 8278949
TI  - [Hereditary intrahepatic cholestasis with lymphedema--Aagenaes syndrome].
AB  - Hereditary intrahepatic cholestasis with lymph oedema is now a well defined
      autosomal recessive inherited syndrome. More than 75% of the known cases (about
      40) are Norwegian, and most of these came from a few communities in the south
      western part of Norway. Cholestasis is present prior to or shortly after birth.
      With modern treatment the cholestasis usually improves considerably during the
      first two years of life, but periods of recurrent cholestasis occur later. In
      some cases, lymph oedema is present at birth, but usually comes to light during
      childhood. Lymph oedema needs continuous treatment. As a rule, the prognosis for
      the liver disease is good, but cirrhosis has developed in about 15% of the
      Norwegian cases. As for the pathogenesis of the cholestasis, the hypothesis is
      that the cause is an anomaly of the lymph function.

PMID- 8278950
TI  - [Chaos and fractals. Are these of interest to medical science?].
AB  - Biological systems are governed by nonlinear dynamics and often appear to be
      random, because the available information, though accurate, is usually
      incomplete. It is important to be aware of the fact that nonlinear deterministic
      systems can behave unpredictably in the long term. Traditional reductionism is
      unable to provide an adequate understanding of such systems. A more global
      description and explanation of forms, features and functions is required. Chaos
      theory and fractal geometry are of value in this respect. This article is an
      introduction to this relatively new field of science and mathematics.

PMID- 8278951
TI  - ["Rough pleasures"--and the good outdoor life. Physicians as pioneers of the
      outdoor life].
AB  - From the middle of the last century, mountain tourism has become an important
      part of our national tradition and culture. The physical activity and the
      pleasure and relaxation achieved by walking in wild areas is believed to have
      beneficial effects on health. Several colleagues in the medical profession were
      early pioneers in mountain walking and in the discovery and description of former
      "white spots" on maps. They communicated their feeling and love for nature, and
      the pleasure gained from their eventful expeditions. They taught us respect and
      concern for our special environment, with its great opportunities for a variety
      of leisure time adventures.

PMID- 8278952
TI  - [The Bartholinian era--anatomy at the time of Christian IV].
AB  - At the time of King Christian IV of Denmark and Norway the University of
      Copenhagen was one of the most famous universities in Europe because of the epoch
      making medical research carried out there. The author presents a dynasty of
      anatomists--the Bartholin family--who dominated medical teaching and science for
      a century.

PMID- 8278953
TI  - [Philippus Aureolus Theophrastus Bombastus von Hohenheim--known as Paracelsus].
AB  - Paracelsus' life is described biographically from his birth in Einsiedeln in
      Switzerland in 1493, via his education during his prolonged wanderings in many
      parts of Europe, until he was appointed Professor of Medicine in Basel in 1527.
      During the period 1524 to 1538 he wrote a number of medical and theological
      treatises which provide some insight into his way of thinking. He maintained that
      there were sides to nature and human beings that scientists had failed to
      explain, but which were of major importance for an understanding of human beings,
      and for practising medicine. The author briefly discusses some of the basic
      concepts which Paracelsus tried to elucidate in the light of his own experience
      and knowledge. Paracelsus died in Salzburg in 1541.

PMID- 8278954
TI  - [Jan Evangelista Purkinje (1787-1869)].
AB  - The author reviews the life and work of the physiologist Jan Evangelista
      Purkinje. In addition to his remarkable achievements as a scientist, Purkinje
      played a distinctive role in the struggle to establish national and cultural
      independence for the Czech people.

PMID- 8278955
TI  - [Herman Wedel Major as seen by Johan Scharffenberg. A critical reassessment].
AB  - Herman Wedel Major (1814-54) was Norway's first psychiatrist. Through his fierce
      engagement on behalf of the mentally disordered Norway became, in 1848, the 4th
      country in the world, just behind France, England and Switzerland, to establish a
      humane law which provided protection and treatment of people suffering from
      mental disorders. This law was way ahead of its time. In this article I focus on
      the fact that J. Scharffenberg (1869-1965), on insufficient grounds, has given
      Major a reputation which does not agree with the concept of Major and his life's
      work held by his family. This lack of conformity was confirmed in 1911 by P.
      Winge (1857-1920). Scharffenberg wrote his first article 60 years after Major's
      death. He claimed to have found evidence for his theory that Major became
      mentally ill. On the basis of Scharffenberg's conclusions this fallacy has hence
      been recorded in Norwegian medical history.

PMID- 8278956
TI  - [Christian Wisbech--his hospital and surgery in the 1820s].
AB  - Christian Wisbech (1801-1869) was medical superintendent of "Bergen civile
      Sygehus" during the period 1825-1848. Some of his annual reports have been
      published. The hospital had 56 beds. The permanent staff included one
      "spisemester" (caterer) and two "sygeopvartersker" (nurses). Christian Wisbech's
      medicine was based on strict scientific principles and pathological anatomy. A
      post-mortem was performed on the deceased. Other current trends in medical
      practice at that time were foreign to him. It is assumed that he was inspired by
      Giovanni Morgagni (1682-1771) and John Hunter (1728-1793). His treatment was
      partly medical and partly surgical. Wisbech treated surprisingly few injuries. A
      possible explanation is the large number of "barbers and surgeons" in Bergen at
      that time. It was probably a centuries-long tradition among the population to go
      to such persons to be treated for broken bones, wounds and other complaints.

PMID- 8278957
TI  - [Puerperal infections. From Semmelweis to current problems].
AB  - Maternity hospitals began to be established in the middle of the 18th century to
      relieve the distress of the poor. As the number of lying-in hospitals increased,
      so did the cases of puerperal sepsis. The death rate from puerperal sepsis in
      Norway was high and remained so until 1934. Semmelweis studied the maternal
      mortality rates in two obstetric clinics in Vienna for the years 1841-46. He
      declared that puerperal fever was transmitted by the doctors who taught in the
      dissecting room and went straight from there into the labour wards. I 1847 he
      instructed all doctors or students to scrub their hands in a solution of chloride
      of lime before they delivered, examined or touched any patient. The haemolytic
      streptococcus was finally proved to be the cause of puerperal sepsis by Louis
      Pasteur in 1879. There was a significant drop in mortality rates in maternity
      hospitals after the introduction of antiseptic and aseptic techniques around
      1880. Deaths from puerperal fever paralleled deaths from erysipelas, and both
      conditions declined after 1934. Puerperal fever and pelvic inflammation is still
      a clinical problem. The author discusses sexually transmitted diseases and
      multibacterial causes.

PMID- 8278958
TI  - [Obstetric care in Ytre Nordhordland 1858-87. A comparison with national
      statistics].
AB  - In Ytre Nordhordland, a rural district of western Norway, the number of
      stillbirths and maternal deaths was 50-60% above the national average. Local
      unskilled midwives assisted with deliveries, but were of little use in the event
      of complications. The first educated midwife was appointed in 1860, the second in
      1874. In this study, multiple regression analyses were undertaken to examine how
      educated midwives and obstetric operations influenced maternal mortality and the
      number of stillbirths during the 30-year period 1858-87. The explained variation
      was 42% for stillbirths, but only 6% for maternal mortality. While the number of
      skilled midwives was associated with fewer stillbirths, the opposite was found
      for obstetric operations, probably because obstetric operations were reserved for
      the most extreme cases. It is concluded that the local doctors' struggle for
      appointment of educated midwives was of greater importance than their obstetric
      skills.

PMID- 8278959
TI  - [Infant nutrition in a historical perspective].
AB  - Throughout history man, with few exceptions, has meant that breast feeding is
      best for the infant. In poor countries with bad hygiene this can still be a
      question of life or death. However, during several millennia up to the end of the
      19th century, there have been many periods and cultures when the upper classes
      have preferred to have wet nurses for their babies. Artificial feeding is known
      from the Roman empire from the time around the birth of Christ. For centuries,
      many misconceptions have had an influence on infant feeding, often with serious
      consequences for the baby and the mother. Since the latter half of the 19th
      century infant feeding based on scientific observations has gradually emerged,
      and further progress is expected in the coming years. Recent research has shown
      that the infant's diet is more important than it was thought to be ten years ago.

PMID- 8278960
TI  - [Sigrid Undset's "views" on the father-son relationship. References in her
      writings].
AB  - Our Nobel prize winner, Sigrid Undset, is famous for her insight into female
      relationships and her descriptions of climate and flora. This article focuses on
      men's gender identity and the relationship between father and son in the Middle
      Ages, compared with our own times. In the light of today's psychological
      knowledge, it is remarkable how clearly she elaborates the characters of "her"
      men. We should therefore read the great authors, in addition to our professional
      papers.

PMID- 8278961
TI  - [The life style of Morgan Kane].
AB  - A series of 83 paperbacks describing the dramatic life of Morgan Kane was
      published in Norway in the period 1966-1982. Morgan Kane was born in 1855 on the
      Santa Fe trail in the United States. He became one of the fastest gunmen of his
      time, and as Texas ranger, US Marshal and Pinkerton agent was frequently involved
      in gunfights and violence. In terms of sales statistics, this series is one of
      the greatest successes in popular literature ever experienced in Norway. The
      present manuscript describes and discusses the health-related habits of Morgan
      Kane; his smoking habits, use of alcohol, gambling, food habits, sexual
      promiscuity and injury-related patterns of behaviour. In population surveys most
      of the health-related behaviours that are characteristic of Morgan Kane are found
      to be moderately, but consistently correlated. It is hypothesized that the direct
      impacts on the health behaviour of the readers are negligible. Furthermore, it is
      proposed that the cluster of health compromising behaviours which are typical of
      Morgan Kane contributes to an image which has considerable appeal.

PMID- 8278962
TI  - [Are physicians more interested in music than other professional groups?].
AB  - 1,031 Norwegian physicians were questioned about their attendance at various
      musical events, and whether they played an instrument or were active in an
      orchestra or a choir. 36% of the physicians had been to the opera or the ballet
      during the last year, and 64% to at least one classical concert. 39% had been to
      a pop, rock or jazz concert. For the first two categories the figures are higher
      than in a group of Norwegian university graduates. 55% of the physicians can play
      an instrument, and 18% do so actively. These figures are also higher than in the
      university graduate group. Participation in an orchestra or choir is highest
      among general practitioners and public health physicians.

PMID- 8278963
TI  - [Music, brain and medicine].
AB  - Music lacks the specific sound-concept association that is characteristic of
      speech, making exchange of information less precise. Nevertheless, verbal
      language has not replaced musical communication. Music is common to all peoples
      and cultures, probably because certain impressions and emotions are communicated
      more successfully by direct musical intuition. Different musical traditions have
      common features which can be explained by acoustic, auditory and neurobiological
      mechanisms. Harmonic (consonant) intervals--octave, fifth, fourth, third--play an
      important role, and are also spontaneously preferred by animals (rats). Pitch and
      chords are simultaneous patterns that are normally controlled by the right (non
      speech) hemisphere of the brain. Rhythm, speech and language, and prosody are
      sequential patterns that are controlled by the left hemisphere. Musical sounds
      are stored as structural memory patterns, analogous to poetry or rhyme,
      independent of comprehension. Simultaneous singing and rhythmic movement
      facilitate initiation and fluency of speech. Musical functions are included in
      neuropsychological test batteries. In medicine, music is used as an alternative
      channel of communication in aphasia and developmental disorders, and in
      psychotherapy.

PMID- 8278964
TI  - [The final year of Gustav Mahler].
AB  - "I am three times without a country; a Bohemian among Austrians, an Austrian
      among Germans, and a Jew among all the peoples of the world". This famous
      quotation is typical of Gustav Mahler (1860-1911) and reflects his difficult and
      stormy life. His rheumatic mitral valve disease, diagnosed in 1907, was probably
      asymptomatic until recurrent throat infections put an end to his life. At the
      time of his death Mahler was at the peak of his career as a conductor, with 90
      concerts scheduled for the 1910-11 season. He had completed his 9th and begun his
      10th symphony, but would his real task as a composer have survived the serious
      domestic crisis and threatened his artistic life? "My time will come" said
      Mahler, and by this he meant the acknowledgement of his music. But this took a
      long time. Today Mahler's music is played all over the world. Without doubt he is
      "eternal among the great".

PMID- 8278965
TI  - [Edvard Grieg's health and his physicians].
AB  - The Norwegian composer Edvard Grieg (1843-1907) suffered from pleurisy at the age
      of 17 years. The tuberculosis infection later also involved his lungs and
      columna. Throughout his whole life, his health was impaired by a destroyed left
      lung and considerable deformity of his thoracic columna. As complications to
      these sequelae, he suffered from numerous respiratory infections. Later he
      developed combined lung and heart failure. Grieg was admitted, many times to
      different spas and sanatoria both in Norway and abroad. In addition he was
      treated by many different doctors, and several of them became his personal
      friends. In this article, the author presents some of these physicians, and
      briefly describes Edvard Grieg's health problems.

PMID- 8278966
TI  - [Use of psychiatrists in security matters].
AB  - 90 clients with uncertain symptoms and diagnosis, especially clients with pain in
      the musculoskeletal system or with minor neurotic symptoms, were examined by a
      psychiatrist ordered by Skedsmo Social Security Office. The number of clients
      with the diagnosis fibromyalgia was strongly reduced. The number of clients with
      somatic diagnosis increased from three to nine, and three cases of psychosis, not
      earlier diagnosed as such, were recorded. The number of clients on sick leave was
      reduced considerably. Rehabilitation for employment was proposed to many clients.
      The evaluation had little impact on clients applying for a disability pension.
      For 28 clients the examination resulted in necessary and important treatment. As
      a whole the examination produced the best results among clients under the age of
      forty.

PMID- 8278967
TI  - [What is community medicine? Frederik Holst (1791-1871)--our pioneer in the
      field].
AB  - Frederik Holst (1791-1871) was professor of medicine at the University of Oslo
      (The Royal Frederiks University in Christiania) from 1824 to 1865, and was one of
      the founding members of modern Norwegian medical science and practice. His main
      fields of interest were public health and community medicine. The author outlines
      Frederik Holst's professional life as an illustration of how medical knowledge
      and reasoning can influence society.

PMID- 8278968
TI  - [Lung function in singers].
AB  - With the intention of conducting a more comprehensive study among students at the
      Department of Music, University of Oslo, a pilot study was carried out at the
      Clinical-physiological laboratory, Ulleval Hospital, in the 1970s. The author
      briefly reviews earlier studies, and compares their findings with those of the
      pilot study. There seems to be no difference between experienced and non
      experienced singers as regards lung capacity, but the ratio residual volume/total
      lung capacity is much smaller for experienced singers, compared with non
      experienced singers. Experienced singers seem to achieve more efficient use of
      pressure and air flow.

PMID- 8278969
TI  - [External cephalic version in breech presentation].

PMID- 8278970
TI  - [Hypoplastic left heart syndrome].

PMID- 8278971
TI  - [Radius fractures in general practice].

PMID- 8278973
TI  - [Preventive work].

PMID- 8278972
TI  - [An effort against smoking].

PMID- 8278974
TI  - [EDTA treatment of patients with atherosclerosis].

PMID- 8278975
TI  - [Omissions of radiologists as co-authors of articles--should we accept it?].

PMID- 8278976
TI  - [Media medicine].

PMID- 8278977
TI  - [The Haydom hospital--from the east sun and the west moon].

PMID- 8278978
TI  - [The Chinese runners' revolution].
AB  - Scientists are discussing possible explanations of the fantastic improvement in
      physical performance achieved by Chinese female runners in 1993. Some
      untraditional procedure must have been used in addition to intense training. The
      author points out that a study conducted almost a decade ago, and reported in
      Acupuncture and Electro-Therapeutics Research (1984; 9: 165-80), showed a marked
      increase in physical performance following low-frequency (2 Hz) transcutaneous
      electrical nerve stimulation (TENS) in athletes competing in swimming, running
      and cycling events. This study was known to the Chinese, and TENS could be one of
      the methods used. Neither this method nor acupuncture are regarded as doping,
      since at present it is impossible to demonstrate that the athletes have received
      such treatment.

PMID- 8278980
TI  - [If, unless, granted that, in case. Cautions and phrases in the medical
      language].

PMID- 8278979
TI  - [The words "weak" and "ill" have many synonyms and dialect terms].
AB  - The meaning of the words "weak" and "ill" tend to overlap. Feeling weak or ill is
      a common symptom in organic as well as psychogenic disorders. In the Norwegian
      language we have found about 200 synonyms and dialect words for weak or ill.
      These 200 words fall naturally into six groups, depending on which aspects or
      analogues of weak or ill they express.

PMID- 8278981
TI  - [Doxycycline poisoning in veal calves].
AB  - Several veal calves that had received doxycycline died suddenly. Post mortem
      examination revealed pulmonary oedema, myocardial degeneration, and myocarditis.
      It is possible that hitherto unknown interactions between doxycycline and other
      compounds may have played a role.

PMID- 8278982
TI  - [Medicine of pet birds].
AB  - This article describes the demands made upon the veterinarian and equipment of a
      practice for companion birds. The case history of an avian patient is also
      described.

PMID- 8278983
TI  - [Sexually hyperactive dog].

PMID- 8278984
TI  - The role of inhibin on pituitary FSH secretion and maturation of pituitary
      gonadal axis in immature female rats.
AB  - The possible physiological significance of endogenous inhibin was evaluated in
      prepubertal female rats during sexual maturation. Ovarian/serum inhibin, serum
      FSH levels were measured from 4th day to 35th day of life by RIA. Serum inhibin
      levels were first detected on 4th day of life, thereafter, progressively
      increasing up to 27th day. Serum FSH levels gradually increased up to the 14th
      day with a sharp fall in the FSH levels on day 15 which afterwards was maintained
      at a lower level. Pregnant mare serum gonadotropin (PMSG) treatment on day 14 and
      day 22 rats showed different patterns of serum FSH and inhibin changes. In 14 day
      group, there was no difference between control and PMSG treatment, but in 22 day
      group, not only significant difference between control and PMSG treatment but
      also inverted relations between FSH and inhibin after PMSG treatment were found.
      It can be postulated from these findings that secretion of inhibin from the
      granulosa cells is initiated by FSH by its direct action on the ovary whereas the
      level of FSH itself is controlled by inhibin after FSH reaches peak values. Also
      it can be inferred that the feedback control mechanism of inhibin seems to be
      established around 3rd week of life.

PMID- 8278985
TI  - Lesions preceding squamous cell carcinoma of the bronchus and multicentricity of
      canceration--serial slicing of minute lung cancers smaller than 1 mm.
AB  - A total of ten minute squamous cell carcinomas smaller than 1 mm were found in
      surgical lung specimens from 108 patients who had roentgenographically occult
      lung cancer. These minute lesions were detected by submitting, in all the 108
      specimens, the whole bronchial tree to 2-mm-thick sequential transverse slicing
      which was then followed by microscopic examination of each slice on an H-E
      stained section. When a focus of minute carcinoma was found, the slice was
      further serially sectioned to study whether there were such carcinoma-related
      lesions as dysplasia or other atypical changes of epithelia, and when there were,
      the spatial relation of these with the carcinoma. It was demonstrated that all
      the minute carcinomas were closely associated with either dysplasia or what we
      call "basal cells with marked atypia", cells with markedly enlarged nuclei
      arranged in linear fashion on the basement membrane. The contiguity of these
      changes with minute carcinoma strongly suggested that they are lesions preceding
      overt carcinoma. Also, there were some minute foci of carcinoma, which, though
      not involving the entire epithelial thickness, proved to have already begun
      microinvasion.

PMID- 8278986
TI  - Clinical and pathological investigation of endometrial mixed mesodermal tumor.
AB  - Four cases of mixed mesodermal tumor (MMT) of uterine origin were histologically
      and cytologically studied. In the case of occurrence of rhabdomyosarcoma, the
      cells in the aspiration smear appeared independently and sporadically and were
      relatively large in size and polyhedral in shape. The cell margins were not
      clearly distinguishable, and the cytoplasm was non-uniformly and heavily stained
      light green in general except for some pale red eosinophilic areas. The swollen
      and elliptical nuclei had a high N/C ratio. The chromatin showed a densely
      stained coarse granular pattern, and the nuclear margin was expanded. On the
      imprint smear, the cells contained abundant cytoplasm with amoeboid protrusions.
      The cytoplasm was light green in general, was filled with granules of various
      sizes which were non-uniformly and heavily stained. The chromatin showed coarse
      granulation, and a large nucleolus was observed.

PMID- 8278987
TI  - Prognostic significance of CT scan in malignant glioma.
AB  - In 91 malignant gliomas treated with radiation therapy, CT scan which was taken
      before treatment was reviewed to examine the significance as a prognostic
      indicator. The irradiation methods and the surgical resectability did not affect
      the survival. Similarly, the tumor location and the grade of the low density area
      (LDA) surrounding the contrast enhanced area (CEA) had no significance on the
      prognosis. As a result of the multi-variate analysis, the histopathologic
      diagnosis, the CEA size and the CEA pattern were significantly important
      prognostic factors. Astrocytoma grade III, a CEA diameter of under 4 cm and a
      homogeneous CEA were favorable indicators of the malignant gliomas. Tumors with a
      heterogeneous or a ring-like CEA in the diameter of more than 4 cm have the worse
      prognosis and should be treated extensively by radiation therapy.

PMID- 8278988
TI  - Numerical density of alveoli in the human lung--measurement using serial thin
      slices as three-dimensional probes.
AB  - The numerical density of alveoli was estimated in a surgical lung specimen taken
      from a female, aged 51, for adenocarcinoma of the left upper lobe. The specimen
      was fixed by intrabronchial infusion with a mixture of polyethylene glycol and
      formalin. Using a special slicer, 36 serial slices were prepared at a thickness
      of 0.2 mm; in these, a rectangular 3-D sampling probe, 2.0 mm x 2.0 mm x 0.2 mm,
      was set, and the number of alveoli contained in it was counted under a stereo
      microscope. After the serial slice were subjected to computer-assisted 3-D
      reconstruction of the acini and supplying airways, two acini, with a volume of
      140 and 104 mm3, respectively, were selected, in each of which five sampling
      probes were set, two in the centriacinar and three in the peripheral region.
      Counting, performed according to the disector rule, gave a mean alveolar
      numerical density of 121/mm3 (SD = 5.6). No significant difference in density
      proved to exist not only between the two acini but between the central and
      peripheral portions of each acinus. This justifies the premise, on which the
      conventional stereological methods have been based, that the numerical density of
      alveoli of the lung is uniformly distributed over the whole organ.

PMID- 8278989
TI  - Improved radioimmunoassay of cholecystokinin (CCK) using OAL-656 by ethanol
      extraction of human plasma.
AB  - In the radioimmunoassay of human plasma cholecystokinin (CCK) using an antiserum
      OAL-656, it has been difficult to get stable fasting values as well as prominent
      postprandial increase. Therefore, we tried to extract human plasma with ethanol
      before the radioimmunoassay, and could solve these problems, that is fasting
      concentrations became stable (16.7 +/- 2.5 pg/ml) (mean +/- S.D., n = 9), and CCK
      concentrations were augmented promptly after feeding and were kept at higher
      levels for a certain period.

PMID- 8278990
TI  - Some features of prostaglandin synthesis of the cancer cells metastasized into
      liver from gastric cancer lesions.
AB  - In order to study the mechanism of cancer metastasis, AH100B rat hepatoma cells
      were transplanted to the stomach of male Donryu rats. Each hepatic metastatic
      nodule was collected with the respective primary gastric lesions. Each sample
      thus obtained was injected separately into the peritoneal cavity of male Donryu
      rats to make free cancer cells; then, intact cancer cells of the hepatic
      metastatic and primary gastric lesions were collected. After washing in
      Dulbecco's phosphate-buffered saline (Ca2+ and Mg(2+)-free, pH 7.2), the definite
      number of the metastatic and primary gastric cancer cells were incubated in the
      phosphate-buffered saline containing [1-14C] arachidonic acid at 25 degrees C for
      30 min. Arachidonic acid metabolites formed during the incubation period were
      extracted and subjected to thin-layer chromatography, followed by
      autoradiography. Each radioactive spot was scraped off the plate and measured for
      its radioactivity. The pattern of the ability to produce PGs was different
      between the cancer cells which metastasized to the liver and those of the primary
      lesions, that is, percentage of PGF2 alpha was higher (p < 0.05) and that of PGE2
      was quite higher (p < 0.01) in the hepatic metastatic cancer cells as compared
      with those of the primary gastric lesion. These results suggest that PGs produced
      by hepatic metastatic cancer cells might play an important role in hepatic
      metastatic formation.

PMID- 8278991
TI  - Prolongation of canine pancreatic islet allograft survival with combined
      rapamycin and cyclosporine therapy at low doses. Rapamycin efficacy is blood
      level related.
AB  - We studied the survival of 5 groups of apancreatic mongrel dogs that received 30
      days of treatment with CsA adjusted to 300 micrograms/L, rapamycin (0.05
      mg/kg/day), both, or no immunosuppression after intrasplenic allotransplantation
      with purified pancreatic islets. Autografts survived indefinitely. Neither CsA
      nor rapamycin alone at low doses showed significant increase in islet allograft
      survival: 6.2 +/- 1.7 and 5.0 +/- 1.1, respectively, versus 3.4 +/- 1.0 days in
      controls. Dogs treated with low doses of both CsA and rapamycin demonstrated
      prolongation of graft function to 23.6 +/- 13.2 days (P < 0.05). These findings
      support synergism between these 2 agents, especially as CsA was not shown to
      increase trough rapamycin blood concentration when given together. In the
      combined treatment group, a significant (r = 0.90, P < 0.001) relationship was
      found between rapamycin blood levels and graft survival. Animals having trough
      rapamycin concentrations > 10 micrograms/L had significantly (P < 0.05) prolonged
      graft survival, which suggests that dosing of rapamycin according to blood levels
      may optimize the effectiveness of the drug. Given at these low doses, combination
      CsA and rapamycin gave no evidence of adverse effects as measured by hepatic and
      renal function tests, histology, or electron microscopy.

PMID- 8278992
TI  - Development of chronic injury and nature of interstitial infiltrate in a model of
      chronic renal allograft rejection.
AB  - A model of chronic renal rejection in the Dark-Agouti to Albino-Surgery rat
      combination is described. In a number of cases, the original allograft was
      replaced by a second Dark-Agouti allograft. Seventy-five percent of rats
      experienced early episodes of rejection that subsided spontaneously. Second
      allografts had better initial renal function. Variable degrees of tubular
      atrophy, interstitial fibrosis, vascular damage, glomerulosclerosis, deposition
      of humoral mediators, and mononuclear leukocyte infiltrate were observed in all
      long-term allografts. Chronic damage increased with time, and was less severe in
      second allografts. At 5 days, total interstitial infiltrate was similar to that
      seen in unmodified rejection, but there was a significant increase in CD4+ cells
      and a decrease in ED2 and IL-2R expression. Subsequently, the total interstitial
      infiltrate decreased with time, although it remained significantly higher than in
      isografts and residual kidneys from uninephrectomized rats. No significant
      decrease over time was seen in numbers of CD4+ and CD45RC+ cells. The latter had
      a marked focal distribution after 100 days. Total leukocyte infiltrate was
      similar in original and second allografts, but there were changes in the
      proportions of leukocyte subpopulations, including significantly lower numbers of
      CD45RC+ cells in the latter. The persistence of CD45RC+ cells throughout the
      course of chronic rejection and their lower numbers in the second allografts
      favors a role for these cells in the development of chronic injury. The model of
      chronic renal allograft rejection characterized in this study will be valuable in
      further studies of the mechanisms of injury in this pathology.

PMID- 8278993
TI  - Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant
      therapy.
AB  - The effectors of cell death in allograft rejection are poorly understood. Oxygen
      derived free radicals (ODFR) may participate in graft destruction. We examined
      the impact of the antioxidants ascorbic acid (AA) and alpha-tocopherol (AT) with
      low dose CsA on rat cardiac allograft survival. Lewis rats that had undergone
      heterotopic abdominal cardiac transplantation with Wistar-Furth allografts (day
      0) were divided into 6 groups. Group 1 was the control group; groups 2 and 3
      received AA (1200 mg/kg), and groups 4 and 5 received AT (800 IU/kg) by gavage
      daily until rejection. Groups 3, 5, and 6 were given CsA (2.5 mg/kg i.m.) days 1
      15. Allograft rejection times (in days) were 7.7 +/- 1, 10.3 +/- 1.5 (P < 0.01
      vs. group 1), 37.1 +/- 6.4 (P < 0.01 vs. group 1, P = 0.0004 vs. group 6), 9.0 +/
      1.4, 26.5 +/- 3.6 (P < 0.01 vs. group 1, P < 0.03 vs. group 6), and 20 +/- 4.9
      (P < 0.01 vs. group 1) for groups 1, 2, 3, 4, 5, and 6. To assess the impact of
      AA on ODFR production, chemiluminescence was performed on zymosan-activated Lewis
      whole blood from control rats and rats administered AA. AA significantly
      decreased peak chemiluminescence (P < 0.05) as compared with nontreated rats
      indicating effective ODFR scavenging. To determine whether AA and AT inhibit
      lymphocyte stimulation, mixed lymphocyte response testing was performed with
      irradiated Wistar-Furth lymphocytes as stimulator cells for Lew responder cells
      from rats treated as groups 3, 5, and 6. CsA significantly suppressed (P < .05)
      proliferation as compared with untreated controls. Neither AA nor AT enhance
      CsA's immunosuppressive effect by mixed lymphocyte response testing. In summary,
      prolongation of allograft survival with antioxidants AA and AT does not result
      from abrogation of lymphocyte responsiveness or alteration in CsA
      bioavailability. Rather, these data suggest that ODFR are involved in allograft
      destruction and support a role for effective antioxidant therapy in the treatment
      of allograft rejection.

PMID- 8278995
TI  - Intraoperative assessment by laser Doppler flowmetry of hepatic perfusion during
      orthotopic liver transplantation in the rat.

PMID- 8278994
TI  - Mechanism of a clinically relevant protocol to induce tolerance of cardiac
      allografts. Perioperative donor spleen cells plus cyclosporine suppress IL-2 and
      interferon-gamma production.
AB  - Many groups have reported that preoperative injection of donor-derived whole
      spleen cells or major histocompatibility complex antigens prolongs organ
      allograft survival in experimental models, but the immunosuppressive mechanism(s)
      responsible remains unclear. A central, confounding issue is how to reconcile
      documentation of comparable levels of mRNA for IL-2 in suppressed versus control
      groups with obvious host hyporesponsiveness. We used a model of tolerance
      induction involving perioperative injection of donor spleen cells and injection
      of CsA at day 2 after transplant to analyze the serial expression of several
      proinflammatory cytokines relevant to development of alloresponsiveness within
      cardiac allografts and recipients' spleens. Four experimental groups of Lewis
      rats receiving vascularized heterotopic cardiac allografts from Brown Norway (BN)
      donors were evaluated: (1) untreated controls; (2) animals receiving
      intraoperative injection of donor BN spleen cells; (3) those receiving a single
      injection of CsA on day 2 post-Tx; and (4) animals given the combination of
      intraoperative BN spleen cells and CsA on day 2 post-Tx. Graft survival was
      significantly prolonged in Lewis rats receiving the combined spleen cell/CsA
      therapy (mean 64 days, with 40% of grafts surviving > 100 days, n = 15) compared
      with acute rejection at about 8 days (range 6-13, n = 20) in each of the 3
      control groups (P < 0.0001). By comparison with acutely rejecting allografts in
      the control untreated group at day 7 post-Tx, allografts in rats receiving the
      combined perioperative spleen cell/CsA treatment showed (1) significantly reduced
      graft cellularity and interstitial edema; (2) significantly decreased features of
      immune activation, including infiltration by mononuclear cells expressing IL-2R
      or proliferating cell nuclear antigen; (3) decreased intragraft expression of the
      cytokines IL-2 and IFN-gamma; and (4) suppression of endothelial activation as
      evidenced by both failure of up-regulation of intracellular adhesion molecule-1
      and maintenance of thrombomodulin expression by graft endothelium. Analysis of
      sections of recipients' spleens showed that spleen cell/CsA therapy led to
      significant reductions versus untreated controls, in expression of IL-2, IFN
      gamma, and IL-2R. Similarly, mixed lymphocyte response cultures showed that
      responder cells from rats receiving combined therapy proliferated by 93-95% less
      than untreated animals. Our results suggest that the efficacy of this clinically
      relevant protocol is associated with suppression of IL-2 or IFN-gamma protein
      production, and that in the absence of such molecules, it appears that T cell
      receptor occupancy by alloantigens readily induces a state of anergy in vivo.

PMID- 8278996
TI  - The effect of xenoreactive antibody and B cell depletion on hyperacute rejection
      of guinea pig-to-rat cardiac xenografts.
AB  - Xenotransplantation between phylogenetically distant species is prevented by
      hyperacute rejection (HAR), a process that is thought to be initiated by the
      binding of naturally occurring xenoreactive antibodies (NAb) to the endothelium
      of the xenograft (Xg) with subsequent activation of the classical pathway of C.
      The relative role of direct alternative pathway C activation in HAR is
      controversial. To evaluate the role of NAb in HAR of discordant rodent Xg, LEW
      rats were treated from the day of birth with i.p. injections of rabbit anti-rat
      IgM antiserum (RARM), or with mAb specific for rat kappa-light chain (OX12) or
      rat class II MHC (14-4-4S, Y-3P, or 10-2.16), in an effort to deplete B cells and
      NAb. These rats then underwent xenotransplantation with discordant guinea pig
      hearts. RARM was effective in depleting rats (n = 5) of B cells, serum IgM, and
      rat NAb directed against guinea pig cells, but guinea pig cardiac Xg survival was
      not prolonged compared with PBS-treated controls (n = 5), possibly due to the
      rabbit NAb specific for guinea pig cardiac tissue that were passively transferred
      in the RARM preparation. Of the anti-B cell mAb used to avoid this passive
      transfer of NAb, mAb 14-4-4S was highly effective (n = 9) in depleting the
      peripheral blood and spleen of B cells and the serum of IgM and NAb. Guinea pig
      cardiac Xg survival, however, was again not prolonged (n = 5), and rejected Xg
      from the B cell- and NAb-depleted recipients demonstrated rat C3 deposition in
      the absence of rat IgM and IgG. This study demonstrates that while neonatal anti
      B cell antibody treatment can effectively deplete B cells and NAb in the rat,
      such treatment does not significantly prolong cardiac Xg survival in this well
      established guinea pig to rat xenotransplantation model. These findings suggest
      that in addition to NAb depletion, inhibition of alternative C pathway activation
      and other humoral mechanisms may be necessary to prevent HAR and allow successful
      xenotransplantation.

PMID- 8278997
TI  - A comparison of four solutions for cold storage of pancreatic islets.
AB  - Clinical pancreatic islet transplantation requires cold storage of islets for
      some hours. The best solution for cold storage will be that which maintains islet
      viability for the longest time. We have examined the viability of rat and human
      islet after storage at 4 degrees C for up to 6 days in Hanks' balanced salt
      solution, University of Wisconsin solution (UW), and 2 modified versions of this
      last solution, Sumimoto D (SD) and histidine-lactobionate (HL). The integrity of
      cold-stored rat and human islets of Langerhans has been examined using supravital
      stains and electron microscopy. In addition, the viability of cold-stored rat
      islets was tested by intraportal transplantation into syngeneic streptozotocin
      induced diabetic recipients. The in vitro studies showed good preservation of
      islets stored in UW, SD, and HL for up to 72 hr. In comparison, storage for
      periods as short as 24 hr in HBSS markedly reduced islet integrity. The
      transplantation studies showed that rat islets cold stored in HBSS solution for
      24 hr were not able to reverse experimental diabetes, whereas those stored in the
      other 3 solutions for 24 hr successfully reversed diabetes within 1 week of
      transplantation. After 48-hr cold storage, only islets preserved in HL solution
      were uniformly capable of producing functioning islet grafts. None of the tested
      solutions was able to maintain islet viability sufficiently to allow successful
      transplantation after more than 48 hr of cold storage. These experiments
      demonstrate that good islet viability is maintained for up to 24 hr of storage in
      UW, SD, and HL, and even after 48-hr cold storage in HL solution, whereas
      preservation in HBSS solution was deleterious to islet viability within 24 hr.

PMID- 8278998
TI  - Effect of protease inhibitor on ischemia/reperfusion injury of the rat liver.
AB  - The purposes of this study were to clarify the role of neutrophilic proteases in
      the pathogenesis of hepatic ischemia/reperfusion injury and to determine whether
      urinary trypsin inhibitor (UTI) pretreatment attenuated liver
      ischemia/reperfusion injury in rats. Livers from male Sprague-Dawley rats were
      subjected to 90 min of no-flow warm ischemia followed by 120 min of reperfusion.
      Rats were divided into a UTI group and a control group. In the control group, 120
      min reperfusion of the liver produced a significant increase in myeloperoxidase
      activity, a significant decrease in ATP and energy charge, and a marked increase
      in the serum aspartate aminotransferase, alanine aminotransferase, and lactic
      dehydrogenase levels. In the UTI group, the myeloperoxidase activity was
      significantly attenuated (P < 0.01), ATP and energy charge were significantly
      improved (P < 0.01 and P < 0.05, respectively), and the elevation in serum
      aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase
      was also markedly suppressed (P < 0.05, P < 0.01, and P < 0.05, respectively)
      compared with the control group. Sections through the livers of control rats
      showed severe hepatocyte necrosis with neutrophil infiltration. In the UTI group,
      there was slight congestion and hepatocyte necrosis. The survival rate after 90
      min liver ischemia was significantly improved compared with that in the control
      group (P < 0.05). The results of this study suggest that pretreatment with UTI
      significantly attenuates liver reperfusion injury, perhaps by inhibiting
      neutrophil proteases.

PMID- 8278999
TI  - Can effluent hyaluronic acid or creatine kinase predict sinusoidal injury
      severity after cold ischemia?
AB  - It is well recognized that current selection criteria used to assess liver grafts
      before implantation are inaccurate and correlate poorly with graft outcome. A
      bench or laboratory-based test that could indicate the extent of liver injury
      immediately before implantation would be a valuable adjunct to clinical
      assessment. Hyaluronic acid (HA) and creatine kinase (BB component; CK-BB) levels
      in the caval effluent after liver perfusion have been suggested as indicators of
      preservation injury. Our objective was to investigate the relevance of preserved
      liver effluent HA and CK-BB as a predictor of early graft function. Perfused
      liver effluent HA and CK-BB levels were measured. Graft function was measured in
      terms of peak serum aspartate transaminase and its level on day 5 postoperatively
      as well as peak bilirubin level and prothrombin time. The cold ischemia time
      (CIT) was recorded. Statistical comparisons were made among HA level, CK-BB
      level, CIT, and graft function parameters. The study was conducted at The Liver
      and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.
      Fifty patients undergoing OLT were studied. HA level was measured in 50 patients
      and CK-BB level in 30 patients. The main outcome measures were graft function and
      graft outcome. The graft function data are grouped according to effluent HA
      levels above or below 400 micrograms/L. Thirteen patients (26%) had a level below
      400 micrograms/L and the remaining 37 (74%) were above this threshold. There were
      no significant differences between the groups for these indicators of graft
      function. There was no difference between the 2 groups for CIT. The overall
      median HA level was 1212 micrograms/L (range 39-4000 micrograms/L). The median
      total CK activity in the perfusate was 302 IU/L (range 118-1155 IU/L). The
      proportion of CK-BB activity from this total was 146 IU/L (8-641 IU/L), or 48% of
      the total CK activity. In a multiple regression analysis with CK-BB activity as
      the dependent variable, there was no demonstrable numerical relationship to graft
      function. In a separate multiple regression analysis similar results were
      obtained for HA. We conclude that the level of HA or CK-BB levels should not be
      used in determining the suitability for implantation of a harvested hepatic
      allograft.

PMID- 8279000
TI  - Maturation and function of human fetal pancreatic cells after cryopreservation.
AB  - If transplantation of endocrine tissue is to become a therapy for a significant
      number of insulin-dependent diabetic individuals, tissue sources other than adult
      human islets will be required. Because human fetal pancreatic cells may offer
      that alternative, we have tried to find the optimal combination of tissue culture
      and cryopreservation methods for use in transplantation. Islet-like cell clusters
      (ICCs), cryopreserved according to reported methods for adult human islets,
      survived poorly after thawing. In contrast, the yield of ICCs was comparable
      after collagenase digestion of fresh and cryopreserved pancreatic fragments.
      However, the ICCs derived from cryopreserved tissue contained a higher proportion
      of nonepithelial cells, and the recovery of insulin was only 28%, as compared
      with freshly cultured cells. These ICCs had a lower DNA content and a higher rate
      of DNA synthesis. Moreover, cryopreserved cells released a higher fraction of
      their insulin content in basal conditions, and their response to theophylline
      stimulation was slightly lower. ICCs generated from cryopreserved fragments were
      able to mature morphologically and functionally in vivo after transplantation
      into athymic nude mice. However, the level and magnitude of the C-peptide
      response did not equal that of grafted freshly cultured ICCs. Our results
      indicate that it is possible to generate ICCs from cryopreserved human fetal
      pancreas with the capacity, after transplantation, to release insulin
      appropriately in response to glucose. However, possibly because undifferentiated
      pancreatic cells may be particularly vulnerable to cryopreservation, current
      methods may need to be improved for optimal tissue retrieval.

PMID- 8279001
TI  - Significance of terminal rinse for rat liver preservation.
AB  - A terminal rinse (TR) is standard practice in liver preservation with University
      of Wisconsin solution (UW) to avoid a potassium load. The fact that sodium
      lactobionate sucrose solution (SLS) is an effective organ preservation solution
      with a low potassium provided an opportunity to evaluate rat liver preservation
      without the TR step. Its importance was investigated in 122 rat liver
      preservation experiments. In study 1, UW and a hydroxyethyl starch-free, modified
      UW (UWm) were used for 20-hr liver preservation followed by either no TR or
      Ringer's lactate TR. The 1-week survival was: UW-TR, 2/14; UW-no TR, 1/6; UWm-TR,
      0/6; UWm-no TR, 5/5 (P < 0.01). In study 2, livers were stored for 30 hr in SLS,
      UW, UWm, and UWm + chlorpromazine 5 mg/L, all without a TR. Nine of 11 rats
      survived 7 days after SLS, but there were no survivors in the other groups (P <
      0.05). Study 3 compared no TR with TR with SLS, Ringer's lactate (RL), or a
      modified Carolina rinse (CRm) after 30-hr SLS preservation. Survival, serum
      aspartate aminotransferase and alanine aminotransferase, and histology were
      assessed. One-week survival of 9/11 rats in no TR was significantly better than
      in the other groups (3/14 in TR-SLS, 0/8 in TR-RL, and 0/14 in TR-CRm, P < 0.01).
      The values of aspartate aminotransferase (mean +/- SE) 3 hr after transplantation
      were 1862 +/- 439 U/L, 3334 +/- 817 U/L, 6591 +/- 1944 U/L, and 7028 +/- 1704
      U/L, respectively, in no TR, TR-SLS, TR-RL, and TR-CRm. There were significant
      differences both in aspartate aminotransferase and alanine aminotransferase
      between no-TR and each of TR-RL and TR-CRm (P < 0.05). Liver specimens from rats
      killed 3 hr after OLT showed only mild injury in the no TR group and severe
      injury in the remaining groups. We conclude that a terminal rinse is harmful in
      rat liver preservation.

PMID- 8279002
TI  - A diabetic rabbit model for pig islet xenotransplantation.
AB  - An alloxan-diabetic rabbit model was established for the testing of the function
      of discordant xenogeneic pig islets isolated and purified from adult pig
      pancreata. The functional state of the pig islet transplants and immunological
      state of the rabbit recipients were assessed. Intraportal transplantation of 0.47
      +/- 0.01 ml of pig islets with estimated 57418 +/- 5020 in number containing an
      estimated insulin content of 33.93 +/- 2.97 units (n = 7; mean +/- SEM) resulted
      in the normalization of blood glucose with a corresponding rise in insulin levels
      in the diabetic rabbit recipients for 2 days. An intravenous glucose tolerance
      test performed in 4 recipients during the normoglycemic period resulted in an
      improved K rate (2.5 +/- 0.4) over the diabetic controls, but this was
      significantly lower than the normal control animals (K rate = 4.5 +/- 0.4; n =
      8). In vitro studies demonstrated that the preformed antibodies detected in the
      rabbit recipients were cytotoxic to the pig islet cells and lymphocytes. Heat
      treatment at 56 degrees C and mercaptoethanol treatment markedly reduced the
      cytotoxic activities of the sera. These findings implicated involvement of
      complement and IgM class antibodies in the killing of the pig islet cells.
      Furthermore, pig islet transplants at the kidney capsule site were coated with
      IgM class antibodies. This study has demonstrated that pig islets can be
      successfully isolated and purified in sufficient numbers for xenotransplantation
      studies in alloxan-diabetic rabbit. The porcine islet-to-alloxan diabetic rabbit
      combination can serve as a highly stringent and useful discordant model for
      assessing the effectiveness of various immunomodulation and immunosuppressive
      regimens. The finding of an optimal approach to immunorejection would potentially
      be applicable to actual clinical islet xenotransplantation in diabetic patients.

PMID- 8279003
TI  - Correlation of rejection of the duodenum with rejection of the pancreas in a pig
      model of pancreaticoduodenal transplantation.
AB  - To assess the correlation of rejection in the duodenum and the pancreas, we
      examined pancreatic and duodenal tissue from pancreaticoduodenal transplants in
      32 outbred Yorkshire Landrace pigs. After streptozotocin-induced hyperglycemia,
      they were transplanted and treated with prednisone, AZA, and CsA.
      Immunosuppression was reduced by 50% weekly and discontinued at 3 weeks. The
      tissues were harvested at necropsy at various time points. Each organ was graded
      for interstitial rejection and vascular rejection separately as no, mild,
      moderate, and severe. All but 1 animal rejected their organs. Complete
      concordance of rejection between duodenum and pancreas considering both
      interstitial and vascular findings was found in 15/32 (47%) animals. In 11/17
      (65%) of the remaining allografts, the pancreas had a higher rejection grade (3
      interstitial, 5 vascular, 3 both) and in 6/17 (35%) the duodenum had higher
      rejection grades (2 interstitial, 4 vascular). Considering interstitial and
      vascular rejection separately, 23/32 (72%) and 20/32 (63%) showed concordance,
      respectively. Most cases (7/9, 78%) of discordant interstitial rejection showed
      higher interstitial rejection grades in the pancreas. Five cases (4 pancreas, 1
      duodenum) showed interstitial discordance of 2 grades or more. Discordant cases
      with higher vascular rejection were 7 pancreas (58%) and 5 duodenum. Five cases
      (3 pancreas, 2 duodenum) showed vascular discordance of 2 grades or more.
      Interstitial rejection was seen alone (11 cases) and with vascular rejection (20
      cases), but vascular rejection was never seen alone. We made the following
      conclusions. (1) Concordance of duodenal and pancreas rejection occurs in 47% of
      cases. (2) Discordant cases usually show higher grades of rejection in the
      pancreas (65%), but the opposite can also occur. (3) Therefore, if duodenal
      biopsies are positive, they are likely to be representative of pancreatic
      pathology, but when negative, they do not rule out rejection of the pancreas. (4)
      Interstitial rejection appears to precede vascular rejection, suggesting that
      factors released during interstitial rejection play a role in endothelial cell
      activation and vascular rejection.

PMID- 8279004
TI  - The significant effect of HLA-DRB1 matching on long-term kidney graft outcome.
AB  - Serotyping and genotyping (polymerase chain reaction with sequence-specific
      oligonucleotide probes method) were conducted on 520 unrelated individuals to
      determine the linkage disequilibrium of HLA-B and HLA-DRB1. Analyses of 511
      kidney transplants (300 related and 211 cadaver recipients) were carried out at 4
      transplant centers using the linkage disequilibrium of HLA-B and HLA-DRB1
      established previously. All transplant recipients received CsA immunosuppression
      and were transplanted from June 1983 to December 1991. There were 51 significant
      linkages formed between HLA-B and HLA-DRB1 alleles (P < 0.05). DRB1-compatible
      transplants experienced a comparable 5-year graft success rate of 94% as did the
      HLA-identical recipients with a 100% 5-year success rate. However DRB1
      incompatible recipients displayed a significantly reduced 5-year graft survival
      rate of 73% (73% vs. 94% P < 0.01). The 5-year graft survival rate of HLA-DR
      incompatible recipients of 71% was compatible to the 73% for HLA-DRB1
      incompatible recipients. No variation of rejection rate for DRB1-compatible
      grafts was seen in any of the 4 transplant centers. The results also indicated
      that HLA-DRB1 compatibility was essential for optimal success rate, regardless of
      HLA class I mismatches. The overall conclusion was that matching for HLA-DR was
      important to achieve optimal kidney graft survival on the molecular level but not
      on the serotyping level.

PMID- 8279005
TI  - Impaired renal function after pregnancy in renal transplant recipients.
AB  - Twenty-two renal transplant recipients had 29 posttransplant pregnancies and 39
      male transplant recipients became fathers to 65 children between 1971 and 1991.
      Of the deliveries of the female patients, 62% took place between the third and
      sixth year after transplantation. Seven patients had 2 pregnancies. Mean follow
      up time after the first posttransplant pregnancy was 7.5 years. The patients
      survived the pregnancy well, but the increase in serum creatinine concentration
      from the prepregnancy level, registered 3 months and 1 year after delivery, was
      higher than in matched control patients without pregnancy at corresponding times
      after transplantation (the increase in serum creatinine was 47.7 and 61.2 mumol/L
      in the pregnant patients versus -2.7 and 5.4 mumol/L in the control patients, P <
      0.0001 and P < 0.02, respectively). All pregnant and control patients were alive
      at the end of follow-up, but the long-term graft survival of those with a
      pregnancy was significantly (P < 0.005) worse than in the control patients. Ten
      year graft survival was 69% in the pregnant versus 100% in the control patients.
      Although 80% of the neonates born to a mother with a transplanted kidney were
      below the mean for gestational age, the weight and length at birth were within
      normal limits and no severe intrauterine growth retardation was documented.

PMID- 8279006
TI  - Surgical and metabolic aspects of liver transplantation for tyrosinemia.
AB  - Tyrosinemia is the diagnosis of a very small percentage of patients undergoing
      liver transplantation worldwide. Tyrosinemia is endemic within our referral area
      however, and fully one-third of the liver transplantations at our institution are
      done for this disease. Since 1986, 15 patients with tyrosinemia (TYR) and 31
      patients with various other indications (non-TYR) have undergone a total of 51
      liver transplantations. The 36-month actuarial survival for TYR patients is 87%,
      compared with 74% for non-TYR patients. Liver transplantation for hereditary
      tyrosinemia and other metabolic disorders without portal hypertension or previous
      portohepatic operations is notably easier to perform. Intraoperative blood loss
      was less, length of hospital stay was shorter, and incidence of infections was
      lower in TYR than in non-TYR patients. Less than 10% of TYR patients had foci of
      hepatocellular carcinoma at the time of transplantation. For this reason, and
      while most patients with tyrosinemia will eventually require liver
      transplantation, our results do not support systematic early transplantation
      before the age of two years.

PMID- 8279007
TI  - Ethnic variations in patient and graft survival after liver transplantation.
      Identification of a new risk factor for chronic allograft rejection.
AB  - The ethnic origin of renal graft recipients is recognized as an important
      determinant of graft survival. In liver transplantation, the effect of racial
      origin has been studied in black American recipients and has suggested a trend
      toward inferior graft survival in this group. In this study, we have analyzed
      outcome of transplantation in a large multiethnic liver transplant program. Non
      Caucasoid recipients had an inferior patient survival compared with Caucasoids
      and, in particular, European Caucasoids at 1, 3, and 5 years after
      transplantation (46.7% vs. 60.2% at 3 years, P = 0.05). Non-European recipients
      had an inferior graft survival compared with European recipients at 1, 2, and 3
      years after transplantation (e.g., north Europeans 53.5%, south Europeans 48.5%,
      Middle Eastern 40%, and non-Caucasoids 27% at 3 years, P < 0.01). Different
      frequencies of chronic allograft rejection in the ethnic groups contributed to
      the rates of graft survival, with the non-European recipients developing chronic
      rejection at over twice the rate of European recipients (12.6% vs. 5.9%,
      respectively, P = 0.002). The findings in this study support the evidence from
      renal transplant programs that the ethnic origin of recipients is an important
      determinant of outcome after transplantation, with increasing frequency of
      chronic rejection in recipients nonindigenous to the donor population
      contributing to the variations in patient and graft survival rates.

PMID- 8279008
TI  - Use of monoethylglycinexylidide as a liver function test in the liver transplant
      recipient.
AB  - The hepatic conversion of lignocaine to monoethylglycinexylidide (MEGX) has been
      used as a real time monitor of liver function in liver transplant recipients.
      Data are reported for the first 4 weeks after transplant in 50 consecutive
      orthotopic liver grafts in 47 adults. The MEGX concentration was significantly
      depressed by approximately 50% in those patients in whom there was a complicated
      clinical course (excluding steroid-sensitive rejection) after transplantation,
      compared with patients in whom major complications did not occur. The MEGX
      concentration in the recipients after transplant was independent of the donor
      MEGX concentration, but, in addition to the patient's clinical status, was
      strongly influenced by the recipients pretransplant biochemical profile, being
      inversely related to the pretransplant bilirubin concentration. MEGX
      concentrations < 25 micrograms/L in the first 36 hr after revascularization were
      predictive of greater morbidity and mortality.

PMID- 8279009
TI  - Epstein-Barr virus serology and Epstein-Barr virus-associated lymphoproliferative
      disorders in pediatric liver transplant recipients.
AB  - Epstein-Barr virus serology was performed before and after transplantation in 116
      patients of a total series of 261 pediatric OLT recipients. Thirty-nine percent
      had no immunity before OLT, but this percentage decreased to 11.2% at 6 months
      and 10.5% at 2 years after transplantation. In this series, 10 children developed
      a B cell lymphoproliferative disease. Four had adenotonsillar involvement, 2 of
      them with associated digestive tract invasion. Three of these are alive, 2 after
      retransplantation for chronic rejection subsequent to arrest of
      immunosuppression. The fourth died from bone marrow aplasia. Three patients with
      multiorgan involvement died from multisystemic failure. The remaining 3 patients
      had a pseudotumoral mass. Two of these are alive, 1 after retransplantation for
      hepatic localization and secondary vascular and biliary complication. The last
      died from cachexia. Four patients developed the syndrome after viral
      reactivation, and 6 after primo infection. Four patients were under FK506 rescue
      therapy. We conclude that a high rate of EBV primo infection is observed in the
      first months after transplantation. A significant percentage will develop EBV
      associated lymphoproliferative disease, which causes death in half of the
      patients, including all these with multiorgan involvement. Half of the patients
      may survive, but because immunosuppression must be stopped, retransplantation for
      chronic rejection is often necessary in survivors.

PMID- 8279010
TI  - Prolonged preservation in University of Wisconsin solution associated with
      hepatic artery thrombosis after orthotopic liver transplantation.
AB  - Hepatic artery thrombosis (HAT) after liver transplantation (LTx) usually
      mandates retransplantation. Prolonged preservation with Eurocollins solution has
      been associated with HAT. We reviewed our experience with 359 LTx patients to
      identify risk factors for HAT. All grafts were preserved in University of
      Wisconsin solution. HAT developed in 12 patients (3%) within 50 days. Seven
      patients were asymptomatic; four presented with biliary sepsis and 1 with poor
      graft function. Two patients had suffered acute rejection; another 2 had severe
      preservation injury. Technical problems accounted for 4 cases; in the remaining
      8, no etiology was found. Diagnosis was at a mean 14.7 days after LTx. One
      patient maintains normal graft function 3 years after LTx without intervention.
      Eight underwent re-LTx, 3 of whom died. Routine surveillance via duplex enabled
      early diagnosis and revascularization in 3 patients; in all 3, no biliary
      complications occurred between 6 and 20 months. Overall graft and patient
      survival after HAT were 33.3% and 75%, respectively. Cold ischemic time (CIT)
      averaged 813 min in patients with HAT and 669 min in those without HAT (P < .05).
      HAT occurred in 7/165 patients with CIT > 12 hr, and in 3/234 patients with CIT <
      12 hr (P = 0.0699). By avoiding CIT > 12 hr, we have recently avoided HAT in 78
      consecutive patients. We conclude that CIT > 12 hr may increase the risk of HAT.
      When HAT is diagnosed before biliary sepsis develops, flow can often be restored
      and retransplantation averted.

PMID- 8279011
TI  - Relationship between graft cytochrome P-450 3A content and early morbidity after
      liver transplantation.
AB  - Cytochrome P-450 3A metabolizes CsA into several metabolites with very limited
      pharmacological activity and toxicity. In 40 liver donors, the relative
      concentrations of P-450 3A was assessed by immunoblot analysis using a specific
      monoclonal antibody exhibited a 10-fold variation (mean = 92 +/- 50 arbitrary
      units [AU]/mg) in levels. Problems consequent upon CsA usage (nephrotoxicity,
      neurotoxicity, and hypertension) occurred in 8 of 34 transplant recipients in the
      immediate postoperative period, and in these 8 patients the problems were always
      associated with low graft P-4503A levels (mean = 52 +/- 19 A.U./mg, P = 0.0003,
      cf. patients with no toxicity). Four of these patients had CsA levels that were
      also high, but 4 had CsA levels in the therapeutic range. Episodes of early graft
      rejection were related to higher P-450 3A levels (mean = 110 +/- 24 A.U./mg).
      Cytochrome P-450 3A levels were also found to be inversely related to CsA whole
      blood levels (assessed with a specific antibody 12 hr after the intravenous
      infusion of CsA at 1 mg/kg in the recipients (P < 0.02). Cytochrome P-450 3A can
      provide information that should allow individualized immunosuppression with CsA
      maintaining therapeutic levels but avoiding toxicity in susceptible individuals.

PMID- 8279012
TI  - Cyclophosphamide as an alternative to azathioprine in cardiac transplant
      recipients with suspected azathioprine-induced hepatotoxicity.
AB  - AZA has been reported to cause liver dysfunction in some recipients of solid
      organ transplants. To assess the safety and efficacy of cyclophosphamide in
      maintenance immunosuppression in the setting of AZA-induced liver dysfunction, we
      retrospectively reviewed the records of 320 surviving cardiac transplant
      recipients in Utah. Cyclophosphamide was substituted for AZA in 29 patients due
      to elevated liver enzymes. Patients were switched to cyclophosphamide 689 +/- 104
      days after transplantation; total follow-up after initiation of cyclophosphamide
      was 540 +/- 56 days. The dose of cyclophosphamide after 2 and 6 months of
      cyclophosphamide therapy was 62 +/- 6 mg/day (0.8 +/- 0.1 mg/kg/day) and 48 +/- 5
      mg/day (0.6 +/- 0.1 mg/kg/day), respectively, compared with 233 +/- 20 mg/day
      (2.9 +/- 0.2 mg/kg/day) of AZA. The substitution of cyclophosphamide for AZA was
      associated with a significant improvement in liver function tests. Liver enzymes
      decreased by up to 49% (P = 0.027), while serum bilirubin decreased by 58% (P <
      0.001). Rejection frequency did not increase; neither corticosteroid nor CsA
      dosage was altered significantly after the substitution of cyclophosphamide.
      Significant bone marrow suppression was not observed; specifically, no
      significant change in white blood cell count or hematocrit occurred.
      Complications of treatment with cyclophosphamide were few; only 1 patient
      discontinued cyclophosphamide because of alopecia. We conclude that
      cyclophosphamide appears to be safe in maintenance immunosuppression, permitting
      the discontinuation of AZA in patients with AZA-induced hepatic dysfunction
      without necessitating the augmentation of either corticosteroids or CsA.

PMID- 8279013
TI  - The effect of fluid therapy on alveolar arterial oxygen gradient in brain-dead
      organ donors.
AB  - Lung transplantation is limited by a shortage of suitable lung donors. Fluid
      loading is widely used to increase blood pressure during donor maintenance. In a
      prospective study, we investigated the effect of fluid loading with lactated
      Ringers solution on pulmonary function in 26 brain-dead adult organ donors. In
      all patients, the initial central venous pressure (CVP) was < 6 mmHg. In 13
      patients, a CVP of 8-10 mmHg was achieved and maintained for 90 min by an
      infusion of lactated Ringers solution. This resulted in a significant increase (P
      < 0.05) in the alveolar arterial oxygen gradient. In 13 patients, the CVP was
      maintained at 4-6 mmHg for 90 min by, if necessary, an infusion of lactated
      Ringers solution. In these patients, no significant change in the alveolar
      arterial oxygen gradient occurred. Pulmonary gas exchange has been shown to be a
      reliable means of evaluating donor lung function. We conclude that crystalloid
      fluid loading to a CVP of 8-10 mmHg may be deleterious to lung function and
      should be avoided in potential lung donors.

PMID- 8279014
TI  - Chronic thromboxane synthase inhibition with CGS 12970 in human cyclosporine
      nephrotoxicity.
AB  - CsA nephrotoxicity in rats is associated with an increase in renal thromboxane
      production. Treatment with selective thromboxane synthase inhibitors or receptor
      antagonists improves renal function in these animal models. In humans, it is
      unclear whether intervention aimed at reducing the effects of thromboxane on the
      kidney will be clinically useful. However, we reported previously that
      thromboxane metabolite excretion is increased in CsA-treated renal allograft
      recipients with evidence of CsA toxicity and that 48-hr intravenous infusion of
      the selective thromboxane synthase inhibitor CGS 13080 improves renal function in
      such patients. We undertook the present study to determine the effect of more
      prolonged treatment with an oral thromboxane synthase inhibitor, CGS 12970, in
      renal transplant recipients taking CsA. We measured glomerular filtration rate
      and p-aminohippurate clearance before and after 4 weeks of treatment with CGS
      12970 in 13 patients with renal allografts who had been treated with CsA for a
      mean 6.3 months and had mild renal insufficiency. Baseline serum creatinine was
      1.8 +/- 0.3. Treatment with CGS 12970 resulted in 83% inhibition of urinary
      thromboxane B2 (TXB2), 93% inhibition of 2,3-dinor-TXB2, and 89% inhibition of 11
      dehydro-TXB2, but no change in the urinary excretion of prostacyclin metabolites.
      However, suppression of urinary thromboxane metabolites to these levels did not
      significantly affect renal function. Glomerular filtration rate was 45 +/- 4
      ml/min/1.73 m2 at baseline and 43 +/- 4 ml/min/1.73 m2 after 4 weeks of treatment
      with CGS 12970. Estimated renal plasma flow was 272 +/- 21 ml/min/1.73 m2 at
      baseline and 251 +/- 38 ml/min/1.73 m2 with thromboxane synthase inhibition.
      Thus, substantial suppression of thromboxane production with CGS 12970 did not
      improve renal function in CsA-treated renal allograft recipients.

PMID- 8279015
TI  - In vivo depletion of xenoreactive natural antibodies with an anti-mu monoclonal
      antibody.
AB  - Hyperacute rejection of vascularized discordant xenografts, such as pig-to
      primate kidney or heart xenotransplants, is thought to be mediated by
      xenoreactive natural antibodies (XNA) of the IgM isotype and the activation of
      the classic pathway of complement. Using the guinea pig-to-rat discordant
      xenograft model, we have developed a potential therapeutic protocol leading to
      long-term depletion of circulating IgM in adult animals. This protocol consists
      of the injection into adult LOU/C rats of an antirat IgM MAb (MARM-7) after
      splenectomy, plasma exchange, and the administration of an anti-B cell
      immunosuppressant, mycophenylate mofetil (RS61443). Splectomized plasma exchanged
      adult rats receiving RS61443 showed strongly decreased IgG and IgM serum
      concentrations for a relatively short period during which these isotypes remained
      nevertheless detectable by a sensitive ELISA technique. In contrast to IgM, IgG
      in serum returned, shortly after the end of this treatment, to normal
      concentrations. Splenectomy alone was able to significantly decrease, for a long
      period (more than 70 days), IgM but not IgG serum concentrations in these rats.
      During this treatment, IgM XNA concentration mirrored total IgM. The injection of
      MARM-7 MAb to adult LOU/C rats was able to deplete circulating IgM and IgM XNA
      for a period of several weeks during which IgM was undetectable by a sensitive
      ELISA technique. Depletion time was dose-dependent--the higher the dose of
      injected MARM-7, the longer the period for which IgM and IgM XNA remained
      undetectable. Moreover depletion of circulating IgM was correlated with the
      detection in the serum of these rats of noncomplexed, free MARM-7. Finally, MARM
      7 administration was significantly more efficacious in rats that had decreased
      levels of circulating IgM after splenectomy, plasma exchange, and administration
      of RS61443. These experiments suggest that the anti-mu approach may allow
      depletion of IgM XNA for a sufficiently long period to test the hypothesis of
      "accommodation" in other xenograft models such as the pig-to-primate xenograft or
      even in ABO-incompatible allografts.

PMID- 8279016
TI  - Carbohydrate antigens of pig tissues reacting with human natural antibodies as
      potential targets for hyperacute vascular rejection in pig-to-man organ
      xenotransplantation.
AB  - Pig tissues were screened by immunofluorescence with lectins, mAb, and human
      natural antibodies for the presence of carbohydrate antigens, which may be
      potential targets for hyperacute vascular rejection in pig to man
      xenotransplantation. The unfucosylated monomorph linear B-antigen was found at
      the surface of all porcine vascular endothelial cells. This pig linear-B antigen
      reacts strongly with the anti-alpha Gal isolectin B4 from Griffonia simplicifolia
      1 and with human natural anti-alpha Gal antibodies specifically purified by
      affinity chromatography on synthetic oligosaccharides containing the terminal
      nonreducing alpha Gal1-->3 beta Gal-R disaccharide. This antigenic activity is
      destroyed by treatment of pig tissues with alpha-galactosidase. The localization
      of this linear-B epitope on vascular endothelium and its reactivity with natural
      human anti-alpha Gal antibodies suggest that it may play a major role in the
      hyperacute vascular rejection of pig to man organ xenografts. The lectin from
      Maackia amurensis reacting with alpha NeuAc2-->3 beta Gal1-->4GlcNAc/Glc was also
      positive on pig vascular endothelium, but we do not know yet whether there are
      human natural antibodies reacting with the carbohydrate recognized by this
      lectin. Epithelial cells of pig renal proximal convoluted tubules, respiratory
      epithelium, pancreatic ducts, and epidermis express the linear-B antigen, but
      they are less likely to trigger a hyperacute vascular rejection because they are
      not directly exposed to the blood. The genetically defined pig A+/A- system
      controls the expression of A and H antigens in pig epithelial cells from renal
      distal and collecting tubules, biliary ducts, pancreatic ducts, large bronchi,
      and digestive mucosa. The pig A antigen may trigger an immune response in human O
      or B recipients if they are transplanted with organs from A+ pigs, but the pig A
      antigen is probably not involved in the hyperacute vascular rejection of a
      xenograft because it is not expressed on vascular endothelium.

PMID- 8279017
TI  - Induction of tolerance to heart allografts in rats using posttransplant total
      lymphoid irradiation and anti-T cell antibodies.
AB  - This study examined whether posttransplant anti-T cell monoclonal or polyclonal
      antibody therapy could provide a window of treatment to allow posttransplant
      total lymphoid irradiation (TLI) to induce tolerance. These experiments were
      conducted in a high responder strain combination of an ACI cardiac allograft into
      a Lewis rat. In this situation, treatment with antibody or posttransplant TLI
      alone is insufficient to induce tolerance, while similar treatments alone have
      been shown to induce tolerance in low responder strains. The affects of three
      anti-T cell therapies were compared: anti-CD4 mAb therapy, anti-CD3 mAb, and
      rabbit antithymocyte globulin (RATG). None of these antibody therapies alone
      prolonged graft survival indefinitely. Combining anti-CD4 therapy with
      posttransplant TLI markedly delayed rejection but failed to induce long-term
      graft survival. Tolerance could be induced by a combination of anti-pan T cell
      antibody (anti-CD3) and TLI, and, all grafts survived beyond 100 days. RATG
      failed to prevent graft rejection when used alone or in combination with TLI.
      However, posttransplant therapy with a combination of RATG, TLI, and single-donor
      blood transfusion resulted in graft survival beyond 100 days. Recipients bearing
      long-term donor grafts rejected third-party (PVG) grafts within 2 weeks. Low
      density donor bone marrow cells used instead of a blood transfusion did not
      facilitate tolerance. The results indicate that monoclonal or polyclonal anti-pan
      T cell antibodies, TLI, and a donor blood cell infusion function synergistically
      in facilitating tolerance to allografts in the posttransplant period.

PMID- 8279018
TI  - Thromboxane and prostacyclin synthesis in experimental pancreas transplantation.
      Changes in parenchymal and vascular prostanoids.
AB  - The principal causes of failure of a pancreas transplant are rejection and
      vascular thrombosis. There is an unusually high attrition rate for pancreas
      transplants, but study models have been difficult to develop. In a rat model that
      allows study of acute rejection to the exclusion of nonspecific effects of
      transplant surgery on the pancreas, in vitro synthesis of prostacyclin (PGI2) and
      thromboxane A2 (TXA2) by transplanted pancreas and the blood vessels transplanted
      with it was measured using an RIA for their stable hydrolysis products 6-keto
      prostaglandin F1 alpha and thromboxane B2 (TXB2). TXB2 synthesis was
      significantly greater in allotransplanted pancreas than isotransplanted pancreas
      from the 5th day after transplantation. Rejection was complete in the allografted
      group 7-9 days after transplantation. 6-Keto-prostaglandin F1 alpha synthesis was
      similar in the pancreas for both allografts and isografts. Similar changes were
      seen in aorta, celiac artery, superior mesenteric artery, and portal vein
      transplanted with the pancreas. In the transplanted aorta, TXB2 was significantly
      greater in the allograft group from the third posttransplant day. A group of CsA
      treated allografts sampled after 9 days had transplanted pancreatic parenchymal
      and vascular prostanoid synthesis in the isograft range. The changes in PGI2 and
      TXA2 synthesis that accompany cellular rejection may mediate vascular failure in
      rejecting pancreas transplants, and changes in PGI2 and TXA2 synthesis in blood
      vessels transplanted with the pancreas could promote early vascular thrombosis.

PMID- 8279019
TI  - Effect of fasting on hepatocytes cold stored in University of Wisconsin solution
      for 24 hours.
AB  - Although there have been improvements in liver preservation, liver dysfunction
      still remains a serious consequence of liver transplantation. This may be related
      to cold ischemic injury since the incidence of dysfunction increases with longer
      preservation times. However, even some livers preserved for short periods of time
      (less than 15 hr) develop liver dysfunction. One possible cause may be the lack
      of adequate nutritional support, and the donor may be exposed to prolonged
      periods of hyponutrition. In this study, we have compared the effects of fasting
      on functions of hepatocytes isolated from the rat. Hepatocytes were cold stored
      in University of Wisconsin solution for 24 hr and analyzed at the end of
      preservation as well as at the end of rewarming in Krebs-Henseleit buffer for 120
      min. The glycogen content of fed cells was 1.57 mumol/mg protein and this was
      reduced by 95% in cells from fasted rats. After cold storage and rewarming,
      hepatocytes from fasted rats lost 84.2 +/- 2.5% of the total cellular lactate
      dehydrogenase versus only 32.7 +/- 3.8% (P < 0.001) in cells from fed rats. Also,
      ATP and reduced glutathione content of fasted cells were significantly reduced,
      free fatty acids were higher (P = 0.0154), and protein synthesis was reduced to
      41% of controls (versus only 88% in fed cells), although there were no
      differences in phospholipid content. When hepatocytes from fasted rats were
      rewarmed in Krebs-Henseleit buffer containing fructose (10 mM), lactate
      dehydrogenase release was reduced from 80% to 34.4 +/- 0.2% and ATP content was
      significantly higher with fructose than without. Hepatocytes from fasted rats,
      therefore, are more sensitive to cold ischemic injury than cells from fed rats.
      The increased sensitivity appears related to the lack of glycogen as a source of
      substrates for metabolism during rewarming. This is supported by the fact that
      addition of fructose, which is metabolized readily by hepatocytes through
      glycolysis, suppressed rewarming injury to cells from fasted rats. The
      nutritional status of the donor, therefore, may play a pivotal role in the
      results of liver preservation and transplantation. Effective donor nutritional
      management may reduce the incidence of liver dysfunction after transplantation.

PMID- 8279020
TI  - Donor-specific skin transplants activate allodestructive T cells in mice
      resistant to neonatal H-2 tolerance induction.
AB  - Mice of the B10 background that are class II I-E nonexpressing demonstrate a
      relative resistance to neonatal induction of tolerance of class I alloantigens
      from I-E-expressing B10 strains. The majority of these injected mice delete donor
      responsive and "I-E-reactive" (V beta 11+) cells in the immediate postinoculation
      period, with many remaining deleted of donor-specific T cells before the
      application of the test skin graft. Utilizing a hemisplenectomy technique in
      B10.S (I-E-) mice that received as neonates MHC-disparate (B10.SxB10.A)F1 (I-E+)
      lymphohematopoietic cells, we determined the proportion of adult mice that
      demonstrated pretransplant donor cell chimerism as well as several functional and
      phenotypic features ascribed to donor responsiveness. Surprisingly, chimeric
      cells were present in the bulk of recipients and many also exhibited a deletion
      of V beta 11+ T cells and a lack of alloreactivity to the donor strain allotype.
      Since chimeric, MLR-, V beta 11-deleted mice would be predicted to be tolerant to
      allograft challenge, we hypothesized that the test skin graft applied in
      adulthood was providing stimulatory signals that overcame this state of
      immunologic unresponsiveness. To examine this issue, injected mice that had been
      evaluated before skin grafting were challenged with donor-specific skin and
      evaluated for the same parameters measured in the pretransplant period. The
      majority (95%) of these mice subsequently rejected the B10.A skin graft in a
      range of 7-14 days. After graft rejection, V beta 11+ cell levels generally
      increased and chimeric cells were typically eliminated. Thus, the ability to
      reject allografts is not predicted by a "nonresponsive" immune phenotype or the
      presence of chimeric cells before application of the test allograft. In fact, the
      graft appears to provide an in vivo stimulus to the reduced numbers of host donor
      specific T cells that results in the removal of chimeric cells and a breakdown of
      the tolerant state. We conclude that application of orthotopic skin grafts
      provides the signal(s) necessary to break class I tolerance induced neonatally in
      the context of I-E disparity.

PMID- 8279021
TI  - Induction of unresponsiveness in rats after either intraportal injection of donor
      antigen or intravenous injection combined with splenectomy.
AB  - Recently, we reported that hepatic allografts are permanently accepted when
      transplanted after intraportal injection (IP) of donor spleen cells (SPCs). The
      mechanism of this effect was investigated using various protocols for antigen
      injection. ACI (RT1a) and Buffalo (RT1b) rats were used as donors and recipients,
      respectively. Experimental groups were divided into the following groups
      depending on treatment: IP, intravenous injection (IV), splenectomy (Spx), and
      intravenous injection after splenectomy (IV+Spx). Accumulation of donor antigen
      in the various organs was examined by injecting 51Cr-labeled SPCs. Cellular and
      humoral responses after SPC injection was assessed by delayed-type
      hypersensitivity response and complement-dependent cytotoxicity (CDC) assay.
      Heterotopic cardiac transplantation and orthotopic hepatic transplantation were
      performed 10 days after each treatment. The accumulation ratio in the liver was
      significantly higher in the IP and IV+Spx groups than in the IV group. Delayed
      type hypersensitivity responses were lower in the IP and IV+Spx groups than in
      the IV or Spx groups. The CDC titer 7 days after inoculation was significantly
      lower in the IP and IV+Spx groups than in the IV group. In order to examine
      whether the treatment actively suppressed the immune response, the animals were
      rechallenged with SPCs given intravenously 10 days after the initial injection.
      Elevation of CDC titer was suppressed in the IP and IV+Spx groups, but not in the
      IV and Spx groups. Significant prolongation of cardiac allograft survival was not
      observed in the IV and Spx groups. Prolongation was observed in the IP and IV+Spx
      groups. The survival of hepatic allografts in the IV group was decreased. No
      significant prolongation of graft survival was observed in the Spx group. In
      contrast, all hepatic allotransplants in the IP and IV+Spx groups survived over
      45 days. These findings suggest that the accumulation of donor SPCs in the liver
      may play an important role in inducing unresponsiveness after intraportal
      injection of donor SPCs.

PMID- 8279022
TI  - Prevention of induction of unresponsiveness to class I antigens by veto activity
      of donor marrow in cylophosphamide-treated mice.
AB  - The survival of skin grafts from B6.C-H-2bm1 (bm1; Kbm1,IAb,IE-,Db) mice was
      prolonged when C57BL/6 CrSlc (B6; H-2b) mice were inoculated intravenously with 9
      x 10(7) spleen cells (SC) plus 3 x 10(7) bone marrow cells from bm1 mice 14 days
      prior to skin grafting. When B6 mice were inoculated i.v. with bm1 cells and
      treated intraperitoneally with 200 mg/kg cyclophosphamide (CP) 2 days later, the
      survival of bm1 skin grafts was not prolonged at all, suggesting antagonism
      between the veto cell-mediated enhancement by donor cells and CP-induced
      enhancement. In order to deplete the veto cells from the tolerogen, SC plus BMC
      were treated with anti-Thy1.2 mAb+C' or CP. The survival of the bm1 skin grafts
      was not prolonged at all in B6 mice inoculated with Thy1.2-treated bm1 or bm1
      cells from CP-treated donors. When B6 mice were inoculated with Thy1.2-treated or
      CP-treated bm1 cells and followed by CP treatment, however, the survival of bm1
      skin grafts was prolonged moderately. These results strongly suggested that the
      unresponsiveness induced with donor-derived veto cells prevents the tolerance
      induction to class I alloantigens (H-2Kbm1) by our protocol of CP-induced
      tolerance. Furthermore, in B6 mice injected with anti-Thy1.2 mAb on day -1 and
      bm1 cells on day 0, the survival of bm1 skin grafts was not prolonged at all.
      However, skin graft tolerance to bm1 antigens was induced when B6 mice were
      injected with anti-Thy1.2 mAb on day -1 and bm1 cells on day 0 followed by CP on
      day 2. These results may also be explained by the depletion of donor-derived veto
      cells in the recipient mice.

PMID- 8279023
TI  - Enhanced skin allograft survival after photodynamic therapy. Association with
      lymphocyte inactivation and macrophage stimulation.
AB  - It has been found previously that peritoneal exposure to hematoporphyrin
      derivative (HpD) photodynamic therapy (PDT) can induce systemic immunosuppression
      of contact hypersensitivity. We have now found that HpD-PDT also significantly
      prolongs survival of murine skin allografts. Normal A/J mice transplanted with
      BALB/c skin rejected the grafts within 10 +/- 0.9 days. Recipient mice treated 24
      hr previously with HpD-PDT rejected skin allografts at 16 +/- 1.2 days. HpD alone
      or irradiation alone had no effect on skin graft survival, nor did HpD-PDT
      administered shortly after grafting. Flow cytometric analyses showed a nearly
      complete depletion of peritoneal lymphocytes 3 days after HpD-PDT. Lymphocyte
      levels were normal in the spleen, an organ not directly targeted by the PDT
      treatment, but the cells were totally unresponsive to Con A and LPS mitogens.
      Conversely, peritoneal HpD-PDT caused a striking enhancement in macrophage
      function as measured by phagocytosis of antibody-coated sheep erythrocytes.
      Humoral immunity to hen egg-white lysozyme was not significantly changed by HpD
      PDT. These results demonstrate that HpD-PDT causes systemic immunosuppression of
      cellular immunity which, in turn, allows prolonged survival of allografts.
      Humoral immunity appears to remain largely unaffected by HpD-PDT and macrophages
      become activated, suggesting that this therapy might be more effective in
      specifically targeting T cell-mediated immunity than current immunosuppressive
      treatments.

PMID- 8279024
TI  - The protective effect of verapamil on mouse islets transplanted under the kidney
      capsule.
AB  - Islets from normal NMRI mice were transplanted under the kidney capsule of
      syngeneic recipients. The graft-bearing mice were divided into 4 groups treated
      daily with cremophor alone (control), cyclosporine (25 mg/kg body wt), CsA in
      combination with the calcium antagonist verapamil (0.4 mg/kg), or verapamil
      alone. After 3 weeks the grafts were removed, analyzed for insulin secretory
      dynamics in a perifusion system, and extracted for their contents of insulin. The
      graft insulin content was significantly decreased by CsA, an effect counteracted
      by verapamil. As compared with controls, all treatments increased the basal
      insulin at 2.8 mmol/L glucose. CsA together with verapamil enhanced the biphasic
      secretory response to 16.7 mmol/L glucose, whether expressed per graft or per
      unit of insulin content. The glucose-stimulated insulin release per graft was
      greater after combining CsA with verapamil than after CsA alone. It is concluded
      that CsA has adverse effects on islets transplanted to the kidney, and that these
      effects can be ameliorated by combining the immunosuppressant with verapamil.

PMID- 8279025
TI  - Evidence that small bowel preservation causes primarily basement membrane and
      endothelial rather than epithelial cell injury.
AB  - The main site of injury induced during small bowel preservation is perceived to
      be the basement membrane and the endothelium of the highly vascularized mucosa,
      an aspect evaluated here in further detail. The effects of preservation were
      studied using a specific basement membrane stain (laminin antibody), an
      endothelial cell stain (factor 8 antibody) and standard histology. In addition,
      mucosal glutaminase activity reflecting enterocyte integrity was measured as
      monitor of the extent of preservation injury. Using a rat model, small bowel
      grafts were harvested, the vascular bed and bowel lumen were flushed, and the
      grafts were stored (4 degrees C) for 1, 6, 9, and 12 hr and transplanted into
      syngeneic hosts. After cold storage prior to transplantation, full-thickness
      small bowel biopsies were obtained for the various tissue preparations.
      Histologic evaluation at the end of the preservation period revealed separation
      of the villous epithelium from the lamina propria that increased with extending
      preservation time. Tissue staining with the laminin antibody disclosed
      progressive changes with increasing preservation intervals. Staining with the
      factor 8 antibody demonstrated also progressive changes, but failed to reflect in
      a gradual fashion increasing endothelial cell injury. Histologic injury became
      more pronounced after transplantation and reperfusion, then showing destruction
      of epithelial cells; the extent of injury correlated with the duration of
      preservation. Glutaminase activity was maintained after cold storage, indicating
      that the enterocytes remained intact during this period, but when assayed after
      reperfusion, glutaminase decreased with increasing preservation intervals and
      increasing histologic mucosal damage. We conclude that cold ischemic injury
      involves primarily the endothelium and the basement membrane, which progresses to
      global mucosal impairment with reperfusion.

PMID- 8279026
TI  - A proposal for improved cadaver kidney allocation.
AB  - The allocation of cadaver kidneys for transplantation should have two objectives:
      a fair distribution of kidneys among the waiting recipients and a high success
      rate. Currently, organ exchange organizations are following mainly a policy of
      success oriented allocation in that the kidneys are distributed according to the
      best achievable HLA match. A consequence of this policy is that patients with
      rare HLA phenotypes experience prolonged waiting times and that there are large
      kidney exchange imbalances among transplant centers. Based on theoretical
      considerations, we described previously the selection routine COMB which was
      aimed at decreasing excessive waiting times. In this study we present an
      extension of this routine called XCOMB which builds on realistic conditions
      according to the current Euro-transplant waiting list. This new procedure
      decreases the average and maximum waiting time, adjusts for rare HLA phenotypes
      and HLA homozygosity, provides for a reasonably balanced kidney exchange rate
      among centers, and guarantees an HLA match distribution and overall transplant
      success rate near the theoretically possible optimum. The program was tested in
      an extensive simulation based on actual data derived from 35,000 cadaver kidney
      transplants. Although more complex than procedures currently in use, the
      program's efficient software allows the selection of a patient within one second
      from a waiting list of 10,000 potential recipients, using readily available
      computer hardware.

PMID- 8279027
TI  - Interleukin-1 is a critical effector molecule during cytokine dysregulation in
      graft versus host disease to minor histocompatibility antigens.
AB  - Cytokines are believed to cause a number of inflammatory diseases. We have
      investigated the role of 3 inflammatory cytokines, IL-1, IL-2, and TNF alpha,
      during graft-versus-host disease (GVHD), a paradigm disease of cytokine
      dysregulation in vivo. Measuring cytokine mRNA transcripts with a quantitative
      polymerase chain reaction technique, we demonstrate that IL-1 transcript levels
      are increased several hundred-fold in GVHD target organs, whereas TNF alpha
      transcripts increase only 4- to 6-fold. Kinetic studies during the first month
      after transplant unexpectedly show that GVHD never induces IL-2 transcripts in
      the skin and only induces IL-2 transcripts in the spleen during the first week,
      whereas levels of IL-1 transcripts continue to increase throughout the entire 4
      weeks. Administration of an IL-1 receptor antagonist after the termination of the
      IL-2 response and after the establishment of GVHD significantly increases long
      term survival, confirming the central role of IL-1 as an effector molecule of
      GVHD and suggesting new therapeutic strategies for this disorder.

PMID- 8279028
TI  - Induction of transplantation tolerance to rat cardiac allografts by intrathymic
      inoculation of allogeneic soluble peptides.
AB  - Since intrathymic (i.t.) injection of UV-B-irradiated spleen cells (SC) or
      purified resting allogeneic T cells, but not resting B cells, dendritic cells, or
      macrophages induces specific tolerance in transiently immunosuppressed
      recipients, we hypothesized that presentation of donor MHC peptide Ag by the host
      thymic APCs may convey a tolerogenic signal to the recipient. This study examined
      if i.t. inoculation of allogeneic soluble Ag obtained from 3 M KCl extracts of
      purified resting T cells can induce specific tolerance to cardiac allografts in
      transiently immunomodulated recipients. We have now shown that i.t. inoculation
      of donor soluble Ag on day -7 combined with 1 ml ALS on days -7 and 0 leads to
      indefinite WF cardiac allograft survival (> 200 days) in Lewis recipients. This
      finding was reproducible in sublethally irradiated (200 rads TBI) ACI recipients
      of i.t. Lewis soluble Ag. In contrast, ACI cardiac allografts were promptly
      rejected in ALS-treated Lewis recipients of i.t. WF soluble Ag, confirming the
      donor specificity of such immunologic manipulation. Extrathymic inoculation of WF
      soluble Ag via the intravenous route in controls failed to prevent normal graft
      rejection in ALS-treated recipients. The long-term unresponsive recipients
      specifically and permanently accepted donor-type, second-set cardiac allografts.
      The observation that thymectomy performed 7 days after i.t. Ag injection led to
      graft rejection strongly suggests that the early phase of induction of donor
      specific tolerance is dependent on the presence of donor alloantigens in the host
      thymus. This approach may have important clinical therapeutic potential in the
      induction of transplantation tolerance.

PMID- 8279029
TI  - The HLA matching effect in lung transplantation.

PMID- 8279030
TI  - Simultaneous allografting and autografting of skin for ulcers in a bone marrow
      transplant patient.

PMID- 8279031
TI  - Coccidioidomycosis in bone marrow transplant recipients.

PMID- 8279032
TI  - Evidence that fasting hyperproinsulinemia after combined pancreas-kidney
      transplantation diminishes over time.

PMID- 8279033
TI  - Inability of effluent hyaluronic acid levels to predict early graft function in
      clinical renal transplantation.

PMID- 8279034
TI  - Significant stenosis of the vena cava following liver transplantation--a six-year
      experience.

PMID- 8279035
TI  - Management of hemobilia after liver biopsy in liver transplant recipients.

PMID- 8279036
TI  - Aneurysm of the celiac artery in a liver allograft.

PMID- 8279037
TI  - Legionella infection in liver transplant recipients: implications for management.

PMID- 8279038
TI  - Active cytomegalovirus infection in hemodialysis patients receiving donor
      specific blood transfusions under azathioprine coverage.

PMID- 8279039
TI  - Decreased cyclosporine concentrations with the addition of an H2-receptor
      antagonist in a patient on ketoconazole.

PMID- 8279040
TI  - Evidence that the thymus has no significant role in donor-specific blood
      transfusion-induced rat renal allograft enhancement.

PMID- 8279041
TI  - Alteration of intestinal brush border membrane lipid composition in rats by
      cyclosporine.

PMID- 8279042
TI  - Cyclosporine-induced nephrotoxicity in the rat. The effect of alpha 1
      adrenoceptor blockade with prazosin.

PMID- 8279043
TI  - Morphological changes of human common bile ducts after extended cold
      preservation.

PMID- 8279044
TI  - Functional study of residual T lymphocytes after specific elimination of
      alloreactive T cells by a specific anti-interleukin-2 receptor Bk chain
      immunotoxin.

PMID- 8279045
TI  - IgM, IgG, and IgA antibodies in human sera directed against porcine islets of
      Langerhans.

PMID- 8279046
TI  - Transmission of Chagas' disease through cadaveric renal transplantation.

PMID- 8279047
TI  - Renal transplantation in Wiskott-Aldrich syndrome.

PMID- 8279048
TI  - A prospective study of technetium-99m-diethylenetriamine pentaacetic acid renal
      allograft scintigraphy in the diagnostic evaluation of graft dysfunction.

PMID- 8279049
TI  - Living-related liver transplantation despite major arterial and venous
      abnormalities.

PMID- 8279050
TI  - The effect of a positive B cell crossmatch on early rejection in cardiac
      transplant recipients.

PMID- 8279051
TI  - Cardiac graft vascular disease. Nonselective involvement of large and small
      vessels.

PMID- 8279052
TI  - Ability of bone marrow cells and lymph node cells to induce tolerance of skin in
      MHC-congenic rats.

PMID- 8279053
TI  - The immunosuppressive qualities of calcium channel blockers.

PMID- 8279054
TI  - Evidence that simultaneous transplantation of a left kidney and adrenal gland may
      result in severe hypertension after clamp removal.

PMID- 8279055
TI  - A global overview and hope for the eradication of poliomyelitis by the year 2000.

PMID- 8279056
TI  - Vaccination against polio. Inactivated polio vaccine used in The Netherlands and
      Burkina Faso.

PMID- 8279057
TI  - Rehabilitation of the patient with poliomyelitis. The Malawi experience.

PMID- 8279058
TI  - Epidemiology of cerebral palsy.

PMID- 8279059
TI  - Prevention of cerebral palsy.

PMID- 8279060
TI  - Community-based rehabilitation programme.

PMID- 8279061
TI  - Epidemiology of epilepsy.

PMID- 8279062
TI  - Epilepsy. A community approach.

PMID- 8279063
TI  - Children and accidents. Epidemiology and prevention.

PMID- 8279064
TI  - Traumatology in north and south.

PMID- 8279065
TI  - Meeting the needs of disabled village children.

PMID- 8279066
TI  - Rehabilitation in Europe: biostatistical or holistic?

PMID- 8279067
TI  - Different ways of community-based rehabilitation.

PMID- 8279068
TI  - A university's response to the need for community-based rehabilitation.

PMID- 8279069
TI  - Childhood epilepsy in Zimbabwe.

PMID- 8279070
TI  - Community approach in epilepsy treatment. The KAWE experience. Kenya Association
      for the Welfare of Epileptics.

PMID- 8279071
TI  - Preventing accidents in childhood.

PMID- 8279072
TI  - A continuing education programme in paediatrics in Tanzania.

PMID- 8279073
TI  - Paediatric aspects of the HEDERA project.

PMID- 8279074
TI  - The balance between preventive and curative care.

PMID- 8279075
TI  - [Evaluation and assurance of quality of care].

PMID- 8279076
TI  - [Therapeutic strategy for adnexal cysts].

PMID- 8279077
TI  - [Vitrectomy in diabetics].

PMID- 8279078
TI  - [Echography and lithiasis of the submaxillary glands].

PMID- 8279079
TI  - [Hormonal parameters and water-electrolyte disorders in primary hypothyroidism].

PMID- 8279080
TI  - [Treatment of palmar and plantar hyperhidrosis by ++ionophoresis].

PMID- 8279081
TI  - [Importance of the connection between blood insulin and glucose in the diagnosis
      of pancreatic insulinomas: 3 case reports].

PMID- 8279082
TI  - [Polyp of the posterior urethra in a boy: case report].

PMID- 8279083
TI  - [Spinal cord compression by intra-dural arachnoid cysts: a case report and review
      of the literature].

PMID- 8279084
TI  - [McCune-Albright syndrome].

PMID- 8279085
TI  - Urinary chemistry of the normal Sprague-Dawley rat.

PMID- 8279086
TI  - Antibacterial activity of the bladder mucosa.
AB  - Antibacterial activity of bladder mucosa is believed to be a host defense against
      infection. In this study we examined the antibacterial activity of the bladder
      mucosa without the effect of voiding. In addition we examined whether the
      property of adherence was advantageous for the organism in contact with the
      bladder mucosa. For this, three adhering and three nonadhering strains of E. coli
      were placed in contact with the bladder mucosa for 4 h in an in vivo rabbit
      model. E. coli grown in broth and applied to 32 bladders increased in titer by 1
      log. E. coli grown in rabbit urine and applied to seven bladders increased in
      titer by 1.2 log. In contrast E. coli inoculated into control vials containing
      broth increased in titer by 2.3 log (P = 0.01). There was no significant
      difference in the titer between adhering and nonadhering strains of E. coli after
      4 h of contact with the bladder mucosa. Bladder mucosa may have an inhibitory
      effect on bacterial growth (regardless of adherence characteristics) and with
      urine flow serves to prevent infection of the bladder urine.

PMID- 8279087
TI  - Collagen arrangements in ureter.
AB  - The collagen fibres of rabbit and human ureter were exposed by digestion with
      trypsin and hyaluronidase. The fibre structure was examined using an SEM and
      examples of the inner and outer fibre structures are shown together with the
      effects of different types of mechanical strain. An interesting difference
      between the arrangements of the inner fibres of human and rabbit was seen where
      the human ureter had a cross-ply structure while in the rabbit it was helical.

PMID- 8279088
TI  - Motility and intraluminal pressure of the ileocolonic junctional zone and
      adjacent bowel in a canine model.
AB  - The exact role of the ileocecal valve (ICV) at the junction of small and large
      bowel is not well understood. Bowel segments used for the construction of urinary
      reservoirs incorporate the ICV. In the Indiana pouch its natural continence is
      used as one principle for achieving continence of the efferent limb. Motor
      activity and pressure in the ICV, the ileum and colon were registered in eight
      dogs. Myogenic activity of the bowel consisted of slow waves, irregular
      spontaneous contractions and superimposed spikes. Pressures of 7.2 +/- 0.3 cmH2O
      were recorded in the ileum and of 5.6 +/- 0.4 cmH2O in the colon. The pressure in
      the ICV was 12.7 +/- 0.4 cmH2O rising to 26.4 +/- 2.2 cmH2O during spontaneous
      depolarization. Balloon dilatation of the ileum resulted in relaxation of the ICV
      in 76% of experiments, whereas colonic distension was followed by a pressure
      increase in the ICV region in 80% of experiments. In 16% of cases a relaxation of
      the ICV area and a weaker response after repeated dilatation was noted. These
      findings make the ICV an unreliable continence mechanism as its long-term
      continence can not be predicted despite intraoperative evaluation. Additional
      measures to ensure consistent continence at the ICV (e.g. electric stimulation)
      need to be studied.

PMID- 8279089
TI  - Stimulated pressure response of the ileocolonic junctional zone and its use as a
      continence mechanism in a canine model.
AB  - Mechanisms for maintaining passive continence in the efferent limb of urinary
      diversions include compression of tissue, peristalsis, equilibration of pressure
      and use of valves. Motor activity and pressure in the ileum, ileocecal valve
      (ICV) and the colon were evaluated in dogs. Spontaneous activity and pressure
      were compared with stimulated pressure response and activity. Stimulation was
      performed at the pelvic nerve and the small nerves in the mesenterium, as well as
      direct neurostimulation of the bowel. Resting pressure at the ICV was 12.7 +/-
      0.4 cmH2O rising to 26.4 +/- 2.2 cmH2O during spontaneous depolarization.
      Stimulation of the pelvic nerve resulted in increased colonic motor activity with
      unchanged pressure. Electric stimulation of small mesenterical nerves to the ICV
      increased pressure in the ICV to 35.0 +/- 4.1 cmH2O, while direct myoelectric
      stimulation of the ICV zone increased the intraluminal pressure to 75.0 +/- 3.2
      cmH2O. Termination of the electric stimulation was followed by a slow decrease of
      pressure to the resting level over a period of 30-45 s. Maintaining continence at
      the ICV with long-term constant or intermittent stimulation seems feasible.

PMID- 8279091
TI  - Ploidy changes between diagnosis and relapse in childhood renal tumours.
AB  - Ploidy patterns, analysed by flow cytometry (FCM) and image analysis (IA), were
      investigated at relapse in a group of six children with renal tumours [five
      Wilms' tumour (WT) and one bone metastasizing renal tumour of childhood (BMRTC)]
      and results compared with diagnostic profiles. IA detected one or more aneuploid
      populations in five of 12 tumours which were diploid on FCM. Patterns in three of
      six patients [two with unfavourable histology (UH) and one with favourable
      histology (FH)] were aneuploid at diagnosis and relapse, two patients (one FH,
      one BMRTC) developed aneuploid features at relapse and one patient with a
      tetraploid tumour was diploid at relapse. Histology patterns were similar at
      diagnosis and relapse in all patients. Three of six patients (two UH, one BMRTC)
      have died of disease. This report highlights (1) the superiority of IA over FCM
      in detecting aneuploid populations and (2) changes in ploidy status which have
      not previously been reported in these tumours. Overinterpretation of DNA status
      at relapse may prove misleading.

PMID- 8279090
TI  - The dynamic pressure response to rapid dilatation of the resting urethra in
      healthy women: an in vivo evaluation of visco-elastic properties.
AB  - The urethral pressure response to a sudden forced dilatation was studied at the
      bladder neck, in the high-pressure zone and in the distal urethra in ten healthy
      female volunteers. The pressure response was fitted with a double exponential
      function of the form Pt = Pequ + P alpha e-t/tau alpha + P beta e-t/tau beta,
      where Pequ, P alpha and P beta are constants, and tau alpha and tau beta are time
      constants; this equation has previously been demonstrated to describe the
      pressure decay following dilatation. On the basis of a theoretical model the
      elastic and viscous constants for the urethral tissues were computed. The results
      showed significant differences along the urethra, with the high-pressure zone
      showing the highest maximum and equilibrium pressures, fastest pressure decay and
      highest elastic coefficient. The pressure response represents an integrated
      stress response from the surrounding structures, which reflects the visco-elastic
      properties of the tissues involved. The findings seem therefore to correlate well
      with the anatomical findings, which have shown a high fibre density of the
      horseshoe-shaped rhabdosphincter in the mid-portion of the urethra. The method
      permits a detailed assessment of static and dynamic urethral responses to
      dilatation which can be applied as an experimental simulation of urine
      ingression, and is therefore presumed to be of value in the evaluation of normal
      and pathological urethral sphincter function.

PMID- 8279092
TI  - Cytokine production by the human bladder carcinoma cell line T24 in the presence
      of bacillus Calmette-Guerin (BCG).
AB  - The study was initiated as an in vitro approach to the situation existing during
      intravesical bacillus Calmette-Guerin (BCG) instillation in patients with
      superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell
      line T24 treated with BCG was investigated. A 24-h treatment of T24 cells with
      BCG resulted in a tenfold higher secretion of interleukin-6 (IL-6) and tumor
      necrosis factor alpha (TNF alpha) when compared with T24 cells treated with
      Escherichia coli, Streptococcus faecalis or a cell wall preparation of Nocardia
      rubra (N-CWS). No secretion of IL-1 beta and IL-2 was detected. Pre-exposing T24
      cells to BCG for various periods of time indicated that a minimum exposure time
      of 0.5-1 h was required to upregulate IL-6 and TNF alpha production. Extending
      the BCG pre-exposure time to 2 and 3 h further increased the rate of cytokine
      production. No significant difference was found, however, between the rate of
      secretion initiated after a 2-h or 3-h pre-exposure period. The amounts of these
      cytokines secreted in the presence of BCG-conditioned medium did not differ
      significantly from the constitutively secreted amounts, excluding an effect of
      products possibly secreted by BCG on the upregulation of IL-6 and TNF alpha. In
      addition, upregulation of cytokine production appeared to be dependent on the
      concentration of BCG. The results suggest that cytokines may be produced by
      urothelial tumor cells after intravesical instillation in patients with
      superficial bladder cancer, which may play a role in the mode of action of BCG.

PMID- 8279093
TI  - Correlation between clinical response and urinary interleukin levels using
      different doses and intravesical administration schedules of interferon-alpha-2b
      combined with epirubicin: a pilot study.
AB  - A total of 62 patients at high risk for recurrence of superficial bladder cancer
      were selected for a study designed to compare the prophylactic efficacy of
      different doses and schedules of sequential intravesical instillations of
      epirubicin and interferon-alpha-2b and to evaluate which sequence could enhance
      the release of cytokines in the urine. Our investigations showed a significant
      increase in urinary concentrations of interleukins in patients who received the
      sequential intravesical administration of epirubicin and interferon-alpha-2b.
      Higher urinary concentrations of interleukins and a lower recurrence rate were
      detected in patients who received interferon-alpha-2b 24h after epirubicin
      instillation.

PMID- 8279094
TI  - The effects of citrate and urine on calcium oxalate crystal aggregation.
AB  - The rate of crystal sedimentation in a suspension of calcium oxalate monohydrate
      (COM) crystals was determined spectrophotometrically in the presence and absence
      of dialysed urine and citrate. A reduced rate of crystal sedimentation after
      stirring was recorded in suspensions containing citrate in concentrations between
      0.33 and 1.67 mmol/l. The sedimentation rate was reduced in the presence of a 0.3
      3.3% concentration of dialysed urine, with increased inhibition of crystal
      sedimentation when the concentration of urine was increased. A comparison of the
      inhibition of COM crystal sedimentation in whole urine and in dialysed urine from
      normal subjects and stone-formers disclosed significantly higher values (P <
      0.05) in the dialysed urine. The results support previous observations that
      physiological concentrations of citrate might efficiently inhibit the aggregation
      of COM crystals. Furthermore even low concentrations of both whole urine and
      dialysed urine are apparently very efficient inhibitors of COM crystal
      aggregation.

PMID- 8279095
TI  - Effect of different types of textile fabric on spermatogenesis: an experimental
      study.
AB  - The effect of different types of textile fabric on spermatogenesis was studied.
      Twenty-four dogs were divided into two equal groups, one of which wore cotton
      underpants and the other polyester ones. Seven dogs wearing nothing were used as
      controls. The underwear was fashioned to fit loosely in the scrotal area so as to
      avoid its insulating effect. It was worn continuously for 24 months during which
      the semen character, testicular temperature, hormones (serum testosterone,
      follicle stimulating hormone, luteinizing hormone, prolactin) and testicular
      biopsy were examined. The garment was then removed, and the same investigations
      repeated through another 12 months. The results were analysed statistically. In
      the polyester group the testicular temperature showed insignificant changes
      during the period when the pants were worn (P > 0.05). By the end of the 24
      months there was a significant decrease in sperm count and motile sperms, with an
      increase in abnormal forms (P < 0.001); the testicular biopsy showed degenerative
      changes. After garment removal the semen character improved gradually to normal
      in 10 dogs; two remained oligozoospermic. There were insignificant changes (P >
      0.05) in hormones during the study. In contrast, the cotton and control groups
      showed insignificant changes (P > 0.05) in all the aforementioned parameters
      during the 36 months of the study. The polyester pants thus had a deleterious
      effect on spermatogenesis in the dogs which was, however, reversible in the
      majority of cases. The cause of this effect is unknown, but it may be assumed
      that the electrostatic potentials generated by the polyester fabric play a role
      in it.

PMID- 8279096
TI  - [The use of the procedures of functional biocontrol in the combined treatment of
      amblyopia].
AB  - Thirty children with dysbinocular and anisometric amblyopia were treated making
      use of a method based on the use of a physiologically based functional
      bioregulation. It is known that in this condition EEG changes recorded in the
      occipital sectors of the brain are indicative of a weakened specific activation
      reaction. To improve vision acuity, the patients were trained to enhance
      activation reaction by EEG monitoring that was used to create an external
      feedback (EEG status-dependent brightness of the screen when watching an animated
      cartoon). The results show that functional bioregulation method may be used both
      alone and in complex with other methods, reducing the treatment duration and
      helping attain a desirable effect in cases previously treated without success.

PMID- 8279097
TI  - [A new method for treating chronic blepharitis using magnetic compounds and an
      alternating magnetic field].
AB  - Discusses a new method of clinical use of alternating magnetic field from 0.1 to
      0.25 T and of a magnetic ointment composition with reduced iron powder in
      patients with chronic blepharitis. Such treatment was found fairly effective,
      reducing the rehabilitation periods 2-3-fold and giving a good clinical effect
      (41-87%).

PMID- 8279098
TI  - [Peripheral vitreochorioretinal dystrophies in myopia patients].
AB  - The problem of retinal detachment prevention is closely connected with a
      competent diagnosis of peripheral vitreochorioretinal dystrophies (PVCRD). The
      present research was aimed at analysis of PVCRD incidence in myopia of various
      degree and of the incidence of pathologic shifts requiring prophylactic laser
      coagulation or cryopexy. A total of 1022 patients (2044 eyes) with myopia of
      various degrees aged 5 to 58 were examined. Sclerocompression method was used in
      ophthalmoscopy in all the cases. PVCRD were diagnosed in 73.2% of patients. The
      detection rate of this condition was directly proportional to myopia degree;
      52.6% in weak myopia, 70.7% in medium-grave myopia, 86.4% in high myopia. The
      detected patients with PVCRD were in need of preventive treatment whatever myopia
      degree: 38.7% of those with weak myopia, 46.9% of those with medium-grave myopia,
      and 46.5% of those with high myopia, 42.4% of patients with myopia on an average.
      Detachment of the retina was diagnosed in 4% of patients with myopia, in 0.5%
      surgical treatment of this condition was needed, and in 3.5% it was subclinical,
      this permitting a prophylactic laser coagulation.

PMID- 8279099
TI  - [The characteristic interrelationships of the anterior chamber angle in myopia].
AB  - Comprehensive ophthalmologic examinations of the anterior chamber angle were
      carried out in 130 patients (259 eyes) aged 16 to 39 (mean age 22.9 +/- 0.55
      years) with myopia of 0.5 to 13.6 diopters. Study of the pattern of gonioscopic
      signs distribution has shown that the most characteristic factor related to
      myopia development and progress is the presence of goniodysgenesis signs, namely,
      expressed development of ligamentum pectinatum iridis, marked anterior position
      of Schlemm's canal combined with a wide anterior chamber corner, and pigmentation
      of anterior chamber corner. Analysis of gonioscopic signs, their mutual
      influences and relationships with other anatomicofunctional parameters will help
      assess the role of these signs in the development of complicated myopia,
      prediction of myopia course, and differential diagnosis of its pathogenetic
      forms.

PMID- 8279100
TI  - [The ophthalmological symptoms of craniopharyngiomas].
AB  - Clinical symptoms of craniopharyngioma, a benign tumor, are determined by its
      effects on the adjacent structures, the optic route being one of them.
      Ophthalmologic symptoms of craniopharyngiomas reflect the tumor localization and
      predominant growth and depend on patient's age. Visual disturbances are among the
      first symptoms of the disease, particularly so in adult patients. The
      pathogenesis of visual disturbances in craniopharyngiomas is determined by
      several components: vascular factor, mechanic influence of a volumic formation
      and brain base major vessels on the optic route structures, toxic effects, and
      the presence of an optic route nervous tissue edema. It should be noted that
      visual disturbances may not manifest up to a certain moment because of a high
      resistance of the optic route nervous tissue.

PMID- 8279101
TI  - [The prognostic significance of tissue-specific antibodies in the extraction of
      cataracts of different etiologies].
AB  - The authors demonstrate a high informative value of preoperative lacrimal fluid
      examinations to predict postoperative uveitis in patients with complicated
      cataracts. Detection of antituberculin antibodies in titers 1:128 or higher is a
      factor of risk of development of a postoperative inflammatory reaction. The risk
      of postoperative uveitis is increased to 100% if antibodies to tuberculin, tissue
      specific retinal S antigen, and lenticular proteins are simultaneously detected
      in the lacrimal fluid.

PMID- 8279102
TI  - [The clinical trial of a prototype of the new LAR-2 serially produced laser
      optometer].
AB  - Based on results of clinical trials of a new commercial laser optometer LAR-2,
      the authors suggest methodologic recommendations for ametropia diagnosis making
      use of this apparatus. The new device can adequately solve the major refraction
      problems: express diagnosis of ametropia, specification of the optimal vision
      correction in selection of eyeglasses, assessment of dynamic refraction. LAR-2
      was found useful in the treatment of vision fatigue and amblyopia. A conclusion
      is made about diagnostic and clinical fitness of LAR-2 laser optometer; some
      minor shortcomings of the device are to be eliminated.

PMID- 8279103
TI  - [The late results of surgery in glaucoma over 5 years. A modification of
      sinusotrabeculectomy].
AB  - Modified sinusotrabeculectomy is technically simple, low traumatic, and therefore
      was used in elderly patients and in those with grave concomitant diseases.
      Sinusotrabeculectomy helps preserve the anterior chamber of the eye during
      surgery, that is why the postoperative period runs a more smooth course. When the
      anterior chamber is emptied during surgery, the anterior chamber recovers slowly
      in the postoperative period in elderly patients and patients with high
      intraocular pressure before surgery at the expense of reduced intraocular fluid
      production, and ciliochoroidal detachment develops more frequently.

PMID- 8279104
TI  - [Conjunctivitis lignosa and hydrocephalus (an unusual association of 2
      diseases)].
AB  - Two siblings, a brother and a sister, with ligneous conjunctivitis and
      hydrocephalus coursing in parallel were described. Both conditions developed
      during the first year of life. Surgery for hydrocephalus was carried out in both
      children and conjunctivitis gradually subsided.

PMID- 8279105
TI  - [The clinical picture, pathogenetic problems and treatment of glaucoma in youth].

PMID- 8279106
TI  - [The blood circulation of the eye in retinal detachment and its surgical
      treatment].

PMID- 8279107
TI  - [Changes in the drainage system of the eye during hydromonitoring exposure].
AB  - A hydromonitoring exposure with a high-velocity pulsed liquid jet aimed into
      Schlemm's canal lumen and a similar exposure with a syringe at a 60 H pressure on
      piston were carried out in isolated eyes. Examinations of stained sections showed
      that hydromonitoring exposure at a pressure of 1 to 5 techn. atm. induced
      destruction of Schlemm's canal internal wall and cyclodialysis. If a higher
      pressure was used, corneal stratification was observed. Hydromonitoring exposure
      at a pressure of less than 1 techn. atm. or an exposure with a syringe induced
      deformation of Schlemm's canal internal wall, dilatation of intertrabecular
      fissures, and ruptures of individual trabecular layers.

PMID- 8279108
TI  - [The combined treatment of amblyopia by the methods of acupuncture reflexotherapy
      and traditional pleoptics].
AB  - Fifty-two children (75 eyes with amblyopia) were treated by acupuncture and
      traditional pleoptics. This complex of treatment was found more effective as
      against traditional pleoptics alone (70 children, 118 eyes with amblyopia) on the
      whole and in the treatment of high amblyopia. The best results were attained in
      children previously treated by pleoptic methods with special equipment (older
      children). Of the 17 eyes with amblyopia resistant to common treatment multiple
      modality treatment resulted in improvement in 10 (58.8%). The effect of treatment
      persisted for 3 months. The first course of such treatment proved to be the most
      effective in the treatment of high amblyopia; starting from the second course the
      condition grew resistant to such treatment, this resistance gradually augmenting.

PMID- 8279109
TI  - [The effect of occlusion of the better seeing eye on the function of the visual
      system in children with unilateral amblyopia].
AB  - Vision acuity and visual evoked potentials (VEP) to a homogeneous light field and
      chess field reversion were studied in children aged 5-6 years with unilateral
      amblyopia before and after 3-month direct total occlusion of the intact eye.
      Occlusion of the intact eye resulted in improvement of the vision acuity and VEP
      of the amblyopic eye, that correlated with the degree of amblyopia. At the same
      time examinations of the intact eyes revealed reduced amplitude of VEP to large
      and increased latency to small chess pattern cells but no changes of the vision
      acuity. The results evidence the necessity of monitoring the occlusion by VEP
      recording to prevent the detrimental effects of visual deprivation on the
      development of the system of vision in a child.

PMID- 8279110
TI  - Efficacy of current EC meat inspection procedures and some proposed revisions
      with respect to microbiological safety: a critical review.
AB  - This paper presents an evaluation of the current EC meat inspection procedures,
      and some of their proposed revisions, in relation to their efficacy in assuring
      the microbiological safety and quality of meat, and the difficulties for health
      authorities and industry in providing such an assurance. It is concluded that
      neither the current nor the proposed revisions of ante and post mortem meat
      inspection procedures alone are sufficient, and that only integrated approaches,
      applied to each step of animal and meat production, will lead to better quality
      meat. Furthermore, for the design of a really effective and flexible long-term
      system of safety and quality assurance it is necessary to undertake a formal
      quantitative assessment of risk.

PMID- 8279111
TI  - Ultrasonographic findings in cows with traumatic reticuloperitonitis.
AB  - The morphological changes in the region of the reticulum were examined
      ultrasonographically in 26 cows with traumatic reticuloperitonitis, and a
      radiograph of the reticulum was also taken. The ultrasonographic examination
      included observations of reticular motility during a three minute period, of
      reticular contours and of adjacent structures such as the diaphragm, the anterior
      dorsal blind sac of the rumen, the ventral sac of the rumen, the spleen, omasum,
      abomasum and liver. In cows with disturbed reticular motility, biphasic
      contractions were slower than normal or indistinct, and the number of
      contractions was reduced. Fibrinous changes appeared as echogenic deposits,
      sometimes accompanied by hypoechogenic fluid. Abscesses had an echogenic capsule
      with a hypoechogenic centre. In seven cows, there was an effusion in the region
      of the reticulum in addition to the morphological changes. The spleen was
      involved in the adhesions in four cows, the omasum in three cows, the liver in
      one cow and the abomasum in one cow. Radiography revealed foreign bodies
      penetrating the reticulum of 12 cows and magnets in the reticulum of seven cows.
      None of these foreign bodies or magnets could be visualised by ultrasonography.

PMID- 8279112
TI  - Paralysis in farmed Arctic char (Salvelinus alpinus) associated with ammonia
      toxicity.

PMID- 8279113
TI  - Benzimidazole resistance of Haemonchus contortus in goats in Malaysia.

PMID- 8279114
TI  - BVA congress.

PMID- 8279115
TI  - Veterinary nursing examination.

PMID- 8279116
TI  - Veterinary nursing examination.

PMID- 8279117
TI  - Veterinary nursing examinations.

PMID- 8279118
TI  - Neglect of aquaculture?

PMID- 8279119
TI  - FeLV vaccination.

PMID- 8279120
TI  - Flank alopecia in dogs.

PMID- 8279121
TI  - Presumed ergotism in a cat.

PMID- 8279122
TI  - Herpesvirus ICP18.5 and DNA-binding protein genes are conserved in equine
      herpesvirus-1.
AB  - The genome of equine herpesvirus-1 (EHV-1) contained three open reading frames
      (ORFs) in a 3.9 kbp BamHI-SmaI fragment at 0.38-0.41 map units in the long unique
      region. The most 5' ORF encoded the carboxy terminus of a protein with 45-55
      percent amino acid homology to the DNA-binding proteins (ICP8-DBP) of four other
      alpha-herpesviruses. The middle ORF translated to a polypeptide of 775 residues
      with 43-55% homology to the ICP18.5 proteins. The most 3' ORF encoded the EHV-1
      glycoprotein B (gB) gene. Three mRNAs of 4.3, 4.4-4.8, and 3.5-3.9 kb
      (corresponding to the three sequenced ORFs) were all transcribed from the same
      strand. The gene order of this group was conserved in all herpesviruses examined.

PMID- 8279123
TI  - Subcloning of HIV-2 nef genes in E. coli and immunological reactivity of
      expressed fusion proteins.
AB  - The nef gene located in the 3' region of the HIV-2 genome encodes an N-terminally
      myristylated protein of 27-35 kD, likely to be involved in the regulation of
      viral transcription. The nef genes of HIV-2 isolates GH-1, ROD, ST, BEN, and
      D194.17 were inserted into E. coli pEX vectors and expression of Nef beta
      galactosidase fusion proteins was detected in stained gels. All fusion proteins
      specifically reacted with a rabbit serum raised against bacterially expressed Nef
      from HIV-2D194.17. Sera from monkeys inoculated with HIV-2BEN or SIVMAC251
      recognized the Nef proteins of only certain HIV-2 isolates. No cross-reactivity
      of these sera with HIV-1 Nef and of a rabbit anti-HIV-1-Nef serum with the
      described HIV-2 Nef fusion proteins was observed.

PMID- 8279124
TI  - Comparative sequence analysis of the coat proteins of biologically distinct
      citrus tristeza closterovirus isolates.
AB  - The genome of citrus tristeza closterovirus (CTV) consists of a 20 kb single
      stranded RNA encapsidated in a 2000 nm long, flexuous particle. Double-stranded
      (replicative form) RNAs purified from CTV-infected tissue were used to prepare
      complementary DNA libraries that involved initial first-strand cDNA synthesis
      followed by selective amplification of the coat protein gene. CTV-specific
      antisera were used to select clones expressing the coat protein. The coat protein
      genes of seven Florida and four exotic isolates that differ in their biological
      properties were cloned and sequenced. The gene is 669 base pairs long and encodes
      a 223 amino acid protein. There was a greater than 80% homology at both
      nucleotide and amino acid levels among all the isolates examined. However,
      comparisons showed that each isolate was found to have several unique amino acid
      residues. Several blocks of amino acid residues were conserved among all the
      isolates. A cluster dendrogram showed greater similarities among groups of mild
      and severe Florida isolates that differed significantly from those of the
      geographically distinct, exotic CTV isolates.

PMID- 8279125
TI  - Nucleotide sequence of the coat protein gene of citrus tristeza virus: comparison
      of biologically diverse isolates collected in Israel.
AB  - The sequences of the coat protein genes of four seedling yellows (SY) and four
      non-SY (NSY) of citrus tristeza virus (CTV) isolates, which were collected in
      Israel over a period of 30 years, were analyzed. Pairwise comparisons showed
      extensive similarities in the nucleotide and amino acid sequences of six isolates
      designated the VT group. This group consists of three NSY isolates that cause a
      very mild CTV reaction on the sensitive combination of sweet orange (SwO) grafted
      on sour orange (SO), and three SY isolates that cause severe SY and SwO/SO
      reactions. MT, a CTV isolate that is consistently nontransmitted by Aphis
      gossypii, was found to be different in two amino acids (Val 103 and Glu 113) from
      each of the A. gossypii transmissible CTV isolates. Sequencing of the cDNA clones
      obtained from ST, a variably transmitted CTV isolate, showed extensive sequence
      variation among the tested clones. The sequence information indicates that the
      current CTV epidemics in Israel are caused by at least two CTV subspecies (VT and
      HT) displaying extensive differences in their coat protein genes.

PMID- 8279126
TI  - PCR detection of amplified 132 bp repeats in Marek's disease virus type 1 (MDV-1)
      DNA can serve as an indicator for critical genomic rearrangement leading to the
      attenuation of virus virulence.
AB  - A radioactive PCR test was developed that amplified the very virulent Marek's
      disease virus-1 (vvMDV-1) DNA sequence containing the 132 bp repeats. In
      apathogenic MDV-1 (CVI 988, Rispens), amplified DNA bands containing multiple
      copies of 132 bp repeats were identified. In the present study this PCR technique
      was used to monitor the passage level of vvMDV-1 in chicken embryo fibroblasts
      (CEF) in which the number of tandem 132 bp repeats was increased. It was found
      that at passage level 32 of vvMDV-1-B isolate, the 132 bp tandem repeat was
      already markedly amplified and its pattern resembled that of the MDV-1 (CVI 988,
      Rispens) vaccine virus DNA. In the vvMDV-1Z strain, amplification of the 132 bp
      repeat was not detectable at a similar passage level. The PCR test demonstrated
      that the apathogenic MDV-1 Md11/75c virus developed by extensive in vitro
      passaging has amplified 132 bp DNA repeats similar to those of the commercial
      vaccine virus (CVI 988, Rispense). It was also found that the pattern of viral
      RNA from infected cells detectable by Northern blot hybridization was markedly
      changed from a 2.4 kb RNA species in cells infected with vvMDV-1 viruses, to four
      RNA species (ranging from 2.2 to 4.4 kb) in cells infected with passage 32 of MDV
      1-B strain, to a very large number of undefined RNA species synthesized in cells
      infected with attenuated MDV-1 viruses (CVI 988, Rispens and Md 11/75c).

PMID- 8279127
TI  - Fowlpox virus encodes a protein related to human deoxycytidine kinase: further
      evidence for independent acquisition of genes for enzymes of nucleotide
      metabolism by different viruses.
AB  - It is demonstrated that fowlpox virus (FPV) protein FP26 located in the HindIII D
      fragment of the genome is related to the human deoxycytidine kinase (dCK) and
      probably possesses the same enzymatic activity. A homologous protein is not
      encoded by vaccinia virus. A multiple alignment of the amino acid sequences of
      the human and FPV dCKs, the thymidine kinases (TK) of herpesviruses, and cellular
      and vaccinia virus thymidylate kinases (ThyK) was generated and the conserved
      motifs, at least two of which are implicated in ATP binding, were characterized.
      An apparent duplication of ATP-binding motif B in the dCKs was revealed, leading
      to the reassignment of one of the catalytic residues. Phylogenetic analysis based
      on the multiple alignment suggested that the putative dCK of FPV probably has
      diverged from the common ancestor with the human dCK at a later stage of
      evolution than the herpesvirus TKs, with the ThyKs being peripheral members of
      the family. These results are compatible with hypothesis that genes for enzymes
      of nucleotide metabolism could be acquired independently by different DNA viruses
      (Koonin, E.V. and Senkevich, T.G., Virus Genes 6:187-196, 1992).

PMID- 8279128
TI  - Use of lambda gt11 and monoclonal antibodies to map the gene for the 60,000
      dalton glycoprotein of infectious laryngotracheitis virus.
AB  - To localize the gene encoding the 60 kD glycoprotein (gp60) of infectious
      laryngotracheitis virus (ILTV), a library of the ILTV genome was constructed in
      the lambda gt11 expression vector. Twelve recombinant bacteriophages expressing
      gp60 epitopes as fusion products with beta-galactosidase were detected by
      immunoscreening with monoclonal antibodies specific for gp60. The ILTV DNA
      sequence contained in one of these recombinants lambda 24-4 was used as a
      hybridization probe for mapping the insert sequence on the viral genome. The gene
      for the gp60 was located at map unit 0.72-0.77 in the unique long region (UL) of
      the ILTV genome. The DNA sequence of the 1.2 kb insert of lambda 24-4 containing
      the gp60 epitope was determined. The majority of deduced gp60 amino acid sequence
      has no homology with any of the known alphaherpesvirus glycoproteins.

PMID- 8279129
TI  - [The effect of rolitetracycline on the level of nonesterified fatty acids,
      phospholipids, and triacylglycerols in ischemic damage to the myocardium].
AB  - Myocardial ischemia developed in rabbits after ligation of coronary artery within
      60 min. Single dose of rolytetracycline 40 mg/kg was administered intravenously
      before or after ligation. Alterations in content of unesterified fatty acids and
      phospholipids were studied in blood serum as well as of unesterified fatty acids,
      phospholipids and triacyl glycerols--in the myocardium. After ligation of
      coronary artery content of unesterified fatty acids and phospholipids was
      increased 2-fold in blood serum as compared with control values, while in the
      ischemic myocardium these substances were increased more than 2-fold and triacyl
      glycerol--about 7-fold. Administration of rolytetracycline before ligation of the
      artery led to a decrease in content of unesterified fatty acids and phospholipids
      in blood serum down to control values; the ligation-induced high content of
      triacyl glycerols and phospholipids in the myocardium was also decreased, while
      alterations in unesterified fatty acids content were not similar.
      Rolytetracycline administered after the artery ligation caused a decrease in
      content of unesterified fatty acids but triacyl glycerols were markedly
      increased. The antibiotic did not affect the lipid content in nonischemized
      tissues of myocardium.

PMID- 8279130
TI  - [Adrenal hormones in the formation of atherosclerotic precursors in adolescents
      with primary arterial hypertension].
AB  - The components of blood lipid spectrum (total cholesterol, triglycerides and high
      density lipoprotein cholesterol) were studied in 131 adolescents (12-18 years
      old) with primary arterial hypertension at various levels of adrenal hormones
      (hydrocortisone and aldosterone) and blood plasma renin activity. The optimal
      ratio of lipid components in blood was detected if concentrations of adrenal
      hormones and blood plasma renin activity were low. Hyperfunction of the adrenal
      cortex in teen-agers contributed both to the development of hypertension and to
      atherosclerotic changes in vessels. This suggests that definite forms of
      hypertension occurred in adults, with specific impairments in the metabolism of
      blood serum lipids, were developed during the juvenile age.

PMID- 8279131
TI  - [The effect of malonic acid on oxidative decarboxylation of pyruvate].
AB  - Effect of malonic acid on the activity of pyruvate dehydrogenase was studied in
      rat brain hemispheres. Malonate was shown to regulate the oxidative
      decarboxylation of pyruvic acid. The rate of the reaction depended on the
      concentration of malonic acid as well as on the content of pyruvate dehydrogenase
      substrates in the experimental samples.

PMID- 8279132
TI  - [Structure-activity features of malate dehydrogenase from human myocardium in
      atherosclerosis].
AB  - A homogeneous preparation of malate dehydrogenase was obtained from human
      myocardium, the enzyme structure-functional properties were studied. Alterations
      in structure characteristics of the enzyme, increase in its hydrophobic moiety,
      decrease of the enzyme activity were observed during impairments in
      atherosclerosis. The alterations of the enzyme properties appear to be involved
      in deterioration of energy metabolism as well as they are related to activation
      of liposynthesis in atherosclerosis.

PMID- 8279133
TI  - [Fatty acid composition and functional status of erythrocyte membranes in
      patients with sepsis].
AB  - Distinct alterations in fatty acid composition and in the functional state of
      erythrocyte membranes were detected in 58 patients with sepsis; these alterations
      were phase-dependent and correlated highly with clinical picture. Considerable
      increase in content of saturated and monounsaturated fatty acids and a decrease
      in concentration of lipoproteins were found in erythrocyte membranes under
      inauspicious conditions of sepsis development. In these patients activities of
      superoxide dismutase and glucose-6-phosphate dehydrogenase were decreased, while
      content of SH-groups was lowered and lipid peroxidation was inhibited. The
      alterations observed in fatty acid composition of erythrocyte membranes and a
      decrease in metabolic activity of red blood cells may be responsible for
      hemolysis in patients with sepsis.

PMID- 8279134
TI  - [Thrombin-like enzymes in snake venoms].

PMID- 8279135
TI  - [The effect of liposome phospholipids in collagen-induced platelet aggregation].
AB  - Influence of the charge-bearing phospholipids containing in liposome membrane on
      collagen-induced platelet aggregation was studied. The aggregation was inhibited
      after preincubation of blood platelets with liposomes containing egg
      lecithin/cholesterol/phosphatidylserine (stearyl amine); the effect was dose
      dependent. Phosphatidylinositol incorporated into liposomes did not affect
      distinctly thrombocytes activation but decreased the rate of cell disaggregation;
      this effect was also dose-dependent. Use of phosphatidylinositol containing
      liposomes did not affect the content of thromboxane and prostacyclin in the
      system. The effect of the charge-bearing phospholipids on platelet aggregation
      observed should be considered in production of medicinal drugs.

PMID- 8279136
TI  - [The status of the adenylate cyclase system in rat myocardium in dystrophic
      degeneration].
AB  - Development of myocardial dystrophy, occurred after left-lateral vagotomy, aorta
      coarctation and novodrine administration, was accompanied by impairments in the
      adenylate cyclase system of rat myocardium at the step of secondary messenger
      production (cAMP) managed by adenylate cyclase of outer membranes. Dystrophic
      degenerations appear to depend on the type of deteriorations in intracellular
      enzymatic systems, which are regulated by cAMP, as shown by dissimilar response
      of myocardium to the agonist effect; this effect was increased in dystrophy
      caused by denervation and was altered only slightly after aorta coarctation and
      novodrine administration.

PMID- 8279137
TI  - [Metabolism of B group vitamins in patients with insulin-dependent and non
      insulin dependent forms of diabetes mellitus].
AB  - Metabolism of vitamins B, involving evaluation of these vitamins content in blood
      and excretion of their metabolites with urine, was studied in adult healthy
      persons as well as in patients with insulin-dependent and -independent forms of
      diabetes mellitus. Distinct alterations in metabolism of vitamin B2 were detected
      in the insulin-dependent diabetes: its content in erythrocytes and the rate of
      excretion with urine were increased. This phenomenon made some problems in
      evaluation of riboflavin consumption in patients with diabetes mellitus of the I
      type, while parameters of vitamin consumption in insulin-independent diabetes
      were similar to those of healthy persons. Parameters of metabolism of vitamins
      B1, B6 and PP were not different in patients with insulin-dependent and 
      independent forms of diabetes mellitus. Rates of excretion of 4-pyridoxic acid, 1
      methyl nicotinamide, thiamine with urine as well as concentration of the
      corresponding vitamins in blood were similar to those parameters of healthy
      persons.

PMID- 8279138
TI  - [The effect of riboflavin supply on metabolism of water-soluble vitamins].
AB  - Increase of vitamin B6 derivatives by 36% in liver tissue, decrease in content of
      thiamine by 20%, of ascorbic acid--by 35%, of oxidized nicotinamide coenzymes--by
      27%, simultaneously with a decrease in excretion of 1-methyl nicotinamide and 4
      pyridoxic acid with urine were observed in rats with alimentary deficiency in
      riboflavin as compared with the animals kept on a ration containing 1/3 of the
      vitamin physiological requirements. The same regularities were detected in adult
      persons and children examined for consumption of vitamins: a decrease in
      excretion of 4-pyridoxic acid and 1-methyl nicotinamide with urine, slight
      decrease in content of pyridoxal coenzymes in blood plasma and of nicotinamide
      coenzymes in erythrocytes were observed in children with deficiency in riboflavin
      close to deficiency of corresponding enzymes in food ration as compared with
      normal level of vitamin consumption. This suggests that evaluation of pyridoxine
      and/or niacin deficiency in food ration should be related with the rate of
      riboflavin consumption.

PMID- 8279139
TI  - [Metabolism of riboflavin and B group vitamins functionally bound to it in
      insulin-dependent diabetes mellitus].
AB  - In 35 children of 9-13 years old with insulin-dependent diabetes mellitus
      distinct alterations in metabolism of vitamin B2 were detected, which were
      manifested as elevated rate of riboflavin excretion with urine and a decrease in
      the vitamin content in erythrocytes, as 1.5-fold increase in activity of
      erythrocyte glutathione reductase and augmented affinity of erythrocyte
      glutathione reductase to exogenous FAD. Alterations in metabolism of riboflavin
      did not involve the vitamin deficiency as shown by analysis of vitamins B6 and PP
      (4-pyridoxic acid and I-methyl nicotinamide, respectively) excretion with urine
      as well as by study of the coenzymes content in blood of healthy and sick
      children with various rates of riboflavin consumption. Rates of 4-pyridoxic acid
      and I-methyl nicotinamide excretion with urine were similar both in healthy
      children of 9-13 years and in children of this age with diabetes mellitus. The
      data obtained suggest that rates of riboflavin consumption in patients with
      diabetes mellitus differed from those of healthy persons; these reasons should be
      taken into consideration in evaluation of vitamins B2 consumption in patients
      with diabetes mellitus.

PMID- 8279140
TI  - [Ascorbic acid level in blood serum in exogenous and endogenous thyrotoxicosis].
AB  - Content of citric acid was studied in blood serum of patients with thyroid
      hyperfunction and of rats with simulated hyperfunction of thyroid gland.
      Concentration of citrate was significantly increased in blood of these patients
      and of the experimental animals as compared with controls. Uncoupling effect of
      thyroid hormones, related to development of thyrotoxicosis, as well as possible
      liberation of citrate from osteal deposits, where its content is about 1%, are
      discussed.

PMID- 8279141
TI  - [Modification of complement components under the effect of cationic proteins from
      leukocytes from donors and leukemia patients].
AB  - Cation proteins (CP) were isolated from leukocytes by means of ion exchange
      chromatography. Enzyme immunoassay showed that these cation proteins modified C3
      component of complement in vitro. CP obtained from healthy volunteers decreased
      the content of C3 purified by affinity chromatography and C3 of blood serum;
      however, content of C3.H2O op C3b-like form and C3a-fragment were not altered.
      Effect of CP isolated from leukocytes of patients with chronic myeloleukemia and
      chronic lympholeukemia on C3 component was less distinct as compared with that of
      healthy volunteers. At the same time, content of C3b-like form was increased the
      presence of CP from patients with myeloleukemia and of C3a-fragment--in the
      presence of the proteins from patients with lympholeukemia. Excess of
      physiologically active C3 fragments, developed under conditions of these
      diseases, may contribute to a decrease in unspecific body resistance.

PMID- 8279142
TI  - [Permeation of pancreatic ATPase through the blood-brain barrier into the
      cerebral parenchyma].
AB  - Penetration of exogenous RNAases, native and albumin polymer-bound, from
      circulation into the brain parenchyma was studied. Native pancreatic RNAase was
      found to extend through the hematoencephalic barrier; maximal enzymatic activity
      was detected within 15-30 min after administration into a rat tail vein. The
      enzyme activity was not observed within 90 min both in blood serum and brain
      tissue. The conjugate of RNAase and human albumin with molecular mass of 300,000
      penetrated through the hematoencephalic barrier. Maximal enzymatic activity was
      estimated within 3-5 hrs after administration and maintained rather high within
      24 hrs in blood and brain parenchyma. This suggests that the preparations of this
      kind are promising in experimental medicine.

PMID- 8279143
TI  - [Phospholipid composition of erythrocytes in patients with chronic kidney
      failure].
AB  - Qualitative and quantitative composition of lipid fractions was studied in
      erythrocytes of 221 patients (16-62 years old) in the terminal step of chronic
      renal failure. The following lipid fractions were studied: total phospholipids,
      monoglycerides, cholesterol, free fatty acids, diglycerides, triglycerides,
      methyl esters of fatty acids, cholesterol esters, lysophosphatidyl choline,
      phosphatidyl serine, lysophosphatidyl ethanolamine, sphingomyelin, phosphatidyl
      inositol, phosphatidyl choline, lysocardiolipin, phosphatidyl ethanolamine,
      cardiolipin, lysophosphatidic acid and phosphatidic acid. The alterations
      observed in the phospholipid composition of erythrocyte membranes appear to occur
      due to intracellular transformations related to specific metabolism in uremia.
      These alterations of phospholipid composition in erythrocyte membranes of
      patients with chronic renal failure, which were found to be intoxication
      dependent, may be used in prognostic evaluation of patients' state under
      conditions of uremia development.

PMID- 8279144
TI  - [Correction of disorders in the monooxygenase system function with
      diethylnicotinamide (cordiamine) in tetrachloromethane- induced and viral
      hepatitis].
AB  - Content of cytochromes P-450 and b5 and the rate of oxidative dealkylation in
      liver microsomes as well as the antipyrine pharmacokinetics were normalized in
      rats with acute CCl4-induced hepatitis after treatment with cordiamine (diethyl
      nicotinamide) at a dose of 40 mg, subcutaneously, 2 times daily within 4 days.
      Cordiamine (30 drops 3 times daily within 8 days) contributed to normalization of
      the hydroxylating reaction in liver tissue of patients with viral hepatitis A,
      estimated by the "antipyrine" test. The drug exhibited stabilizing effect on
      hydrophobic interactions in microsomal membranes; diethyl nicotinamide possessed
      antiradical and vitamin properties.

PMID- 8279145
TI  - [Measurement of the level of nerve growth factor in murine blood serum].
AB  - Different values of nerve growth factor (NGF) concentrations, estimated in mice
      blood, were obtained as a result of the following reasons: 1) use of various
      procedures for estimation, 2) interaction of beta-NGF with high molecular blood
      serum proteins and 3) presence of a variety of the nerve growth proteins in mice
      blood: from complex to subunit forms of the protein including intermediate
      associations.

PMID- 8279146
TI  - [Effect of acute hypoxia on the phospholipid composition of the cell, microsomal
      and mitochondrial membranes of rat brain and liver].
AB  - Tissue-dependent alterations in composition of phospholipids, studied by means of
      thin-layer chromatography, were detected in plasma, microsomal and mitochondrial
      membranes of rat brain and liver tissues after influence of acute hypoxia in the
      altitude chamber at a "height" of 12,000 m 3-9 min. These alterations were
      maintained within 2 weeks after the acute hypoxia effect in all the membranes
      studied, while they were most distinct in plasma and mitochondrial membranes. In
      the group of hypoxia-stable rats the alterations in phospholipids were more
      pronounced as compared with the group of less stable animals.

PMID- 8279147
TI  - [Fatty acid composition of lecithin and cholesterol esters of high density
      lipoproteins from blood of humans, some mammals, and fish].
AB  - Fatty acid composition of lecithin and cholesterol esters was studied in high
      density lipoproteins obtained from blood serum of 20 male volunteers, 10 pigs, 10
      rats and 30 burbots (Lota lota); the study was carried out using isolation
      (precipitation) of the lipoproteins, thin-layer chromatography of lipoproteins
      and gas liquid chromatography of fatty acids. The findings suggest that the fatty
      acid composition of the preparations studied may serve as a more exact index of
      lipid metabolism than the serum levels of individual lipoproteins.

PMID- 8279148
TI  - [Chromatomass spectrometric determination of free fatty acids in blood serum].
AB  - Complete analysis of blood serum free fatty acids was carried out after
      methylation of the acids in the mixture containing methanol-acetyl chloride 50:1
      and subsequent evaluation of their methyl esters using a gas chromatography
      analyser. Standard mixtures of free fatty acids and their methyl esters were
      analyzed before study of blood serum free fatty acids; composition of fish-liver
      oil (Far Eastern mackerel), containing definite fatty acids was also studied.
      Combination of gas chromatography and mass spectrometry enabled to identify all
      the free fatty acids and to detect their main characteristics (time of retention,
      typical mass spectrum).

PMID- 8279149
TI  - [Determination of glycosylated hemoglobin by affinity chromatography on boron
      phenylagarose].
AB  - When Hb AIc was estimated by affinity chromatography where boron phenyl-agarose
      was used as a sorbent, the highest rate of Hb AIc binding with the sorbent was
      detected at pH 8.5-9.0 while the maximal elution of the protein occurred at 0.3
      0.5 M concentration of sorbitol used as an eluent. Content of Hb AIc, estimated
      in 56 patients with insulin-dependent diabetes mellitus, constituted 12.3 +/-
      0.4%, while in 20 healthy volunteers it was equal to 5.4 +/- 0.2%, which are
      consistent with the literature data obtained by other methods. At the same time,
      the data of Hb AIc estimation by means of affinity chromatography correlated
      exactly with the results of ion exchange chromatography (r = 0.98), thus
      corroborating the validity of the procedure used. Only the stable ketoamine
      fraction of Hb AIc was found to interact with boron phenyl-agarose.

PMID- 8279150
TI  - [Certain aspects of obtaining urinary steroids].

PMID- 8279151
TI  - Helicobacter pylori and peptic ulcer disease.
AB  - Medical therapy for duodenal or gastric ulcer disease has traditionally involved
      gastric acid antisecretory therapy for 4 to 8 weeks to promote initial healing
      and indefinitely to prevent recurrences of ulcer. The discovery of Helicobacter
      pylori in most patients with peptic ulcer disease has led to a change in this
      approach. Therapy designed to eradicate H pylori may facilitate ulcer healing
      with acid antisecretory agents and, more important, may greatly reduce the
      incidence of ulcer recurrence, obviating the need for maintenance antisecretory
      therapy. Regimens designed to eradicate H pylori are difficult to comply with,
      however, and are associated with adverse effects in some patients. In this
      article we review the diagnosis and treatment of H pylori infection in patients
      with peptic ulcer disease and make recommendations regarding the use of
      conventional ulcer therapies and therapies designed to eradicate H pylori.

PMID- 8279152
TI  - Fatal isoniazid-induced hepatitis. Its risk during chemoprophylaxis.
AB  - Isoniazid chemoprophylaxis has long been known to be a highly effective means of
      preventing silent tuberculous infections from spreading to active disease. There
      has been much controversy, however, about the risk it carries for fatal
      hepatotoxicity. In this article I review the rate of fatal isoniazid-induced
      hepatitis during chemoprophylaxis that is done according to current monitoring
      guidelines. Information was obtained from a MEDLINE literature search and a
      survey of tuberculosis control officers in large metropolitan areas throughout
      the country. Data were included of patients who were monitored according to the
      American Thoracic Society's guidelines or who were treated after 1983 when the
      guidelines were published. The pooled results of the published studies showed no
      hepatotoxic deaths in 20,212 patients in whom prophylaxis was started. The
      unpublished data showed 2 deaths in 182,285 patients, for a combined rate of
      0.001% (2 of 202,497). The death rate for those older than 35 years was estimated
      to be 0.002% (1 of 43,334). This rate is significantly lower than was previously
      estimated and should be used to reevaluate the benefit of preventive therapy for
      tuberculin-reactive patients older than 35. The risk of fatal isoniazid-induced
      hepatitis is negligible for all ages when patients are routinely monitored for
      liver toxicity.

PMID- 8279153
TI  - How house officers cope with their mistakes.
AB  - We examined how house officers coped with serious medical mistakes to gain
      insight into how medical educators should handle these situations. An anonymous
      questionnaire was mailed to 254 house officers in internal medicine asking them
      to describe their most important mistake and their response to it; 45% (N = 114)
      reported a mistake and completed the questionnaire. House officers experienced
      considerable emotional distress in response to their mistakes and used a variety
      of strategies to cope. In multivariate analysis, those who coped by accepting
      responsibility were more likely to make constructive changes in practice, but to
      experience more emotional distress. House officers who coped by escape-avoidance
      were more likely to report defensive changes in practice. For house officers who
      have made a mistake, we suggest that medical educators provide specific advice
      about preventing a recurrence of the mistake, provide emotional support, and help
      them understand that distress is an expected concomitant of learning from the
      experience.

PMID- 8279154
TI  - Hypersensitivity pneumonitis.
AB  - Although the cause and development of most inflammatory and fibrotic interstitial
      lung diseases are unknown, both the antigenic stimuli and the immunopathogenic
      mechanisms that produce the syndrome of hypersensitivity pneumonitis have been
      well described. Hypersensitivity pneumonitis is a group of related inflammatory
      and fibrotic interstitial lung diseases that result from hypersensitivity immune
      reactions to the repeated inhalation of antigens derived from fungal, bacterial,
      animal protein, and reactive chemical sources. Immune complex-induced
      inflammatory reactions initiate acute lung injury; T cell-mediated
      hypersensitivity reactions perpetuate it and induce chronic inflammatory,
      granulomatous, and fibrotic responses in the interstitium of the lungs. Because
      the natural history of many interstitial lung diseases of unknown causes involves
      the progressive evolution through these same phases, knowledge about immune
      pathogenesis gained from studies of hypersensitivity pneumonitis may provide a
      way to understand the causes and development of other interstitial lung diseases.

PMID- 8279157
TI  - Ultrasonography in blunt abdominal trauma.
AB  - The Council on Scientific Affairs of the California Medical Association presents
      the following inventory of items of progress in emergency medicine. Each item, in
      the judgment of a panel of knowledgeable physicians, has recently become
      reasonably firmly established, both as to scientific fact and important clinical
      significance. The items are presented in simple epitome, and an authoritative
      reference, both to the item itself and to the subject as a whole, is generally
      given for those who may be unfamiliar with a particular item. The purpose is to
      assist busy practitioners, students, researchers, and scholars to stay abreast of
      these items of progress in emergency medicine that have recently achieved a
      substantial degree of authoritative acceptance, whether in their own field of
      special interest or another. The items of progress listed below were selected by
      the Advisory Panel to the Section on Emergency Medicine of the California Medical
      Association, and the summaries were prepared under its direction.

PMID- 8279156
TI  - Controversies in patient selection for liver transplantation.
AB  - A variety of specific conditions often stimulate controversy regarding candidacy
      for liver transplantation. We review the published experience with liver
      transplantation for alcoholic liver disease, fulminant and chronic hepatitis B,
      and hepatocellular carcinoma and transplantation in older subjects. Liver
      transplantation for alcoholic liver disease and in subjects older than 60 years
      is becoming less controversial because recent data demonstrate that these
      patients have excellent survival and good quality of life after transplantation.
      Only 10% to 15% of persons with alcoholism return to drinking after
      transplantation, and most do so only transiently. Liver transplantation for
      patients with hepatitis B virus infection or primary liver cancer is more
      problematic because recurrent disease is common in both conditions. After
      transplantation for chronic hepatitis B, 80% to 90% of patients have reinfection
      of the allograft and long-term survival is 45% to 50%. Patients receiving
      transplants for hepatocellular carcinoma have only 20% to 30% long-term survival,
      but these survivors are cured of malignancy. Data are presented to support
      continued liver transplantation for chronic hepatitis B and hepatocellular
      carcinoma; however, patients must be selected based on factors that predict a
      favorable outcome, and experimental therapies should be employed to explore ways
      to improve the existing survival rates.

PMID- 8279155
TI  - Androgen deficiency and aging in men.
AB  - Androgen levels decrease with age in men. Androgen deficiency in men older than
      65 years leads to asthenia, a decrease in muscle mass, osteoporosis, and a
      decrease in sexual activity. Androgen deficiency has been reported to cause
      changes in mood and cognitive function. The combination of these factors results
      in impaired quality of life in older men. Androgen replacement therapy in
      hypogonadal men increases bone and muscle mass, enhances muscle and
      cardiovascular function, and improves sexual function and general well-being;
      whether elderly men experience benefits of androgen replacement is not known.
      These benefits have to be weighed against the possible adverse effects of
      prostate and cardiovascular diseases. Careful long-term studies are needed to
      assess the risk-to-reward ratios of androgen or other hormone replacement therapy
      before treatment strategies similar to estrogen therapy for postmenopausal women
      are implemented.

PMID- 8279158
TI  - Stabilizing and resuscitating patients with automatic implantable cardioverter
      defibrillators.

PMID- 8279159
TI  - Options for sedating children.

PMID- 8279160
TI  - Dealing with violence in the prehospital setting.

PMID- 8279161
TI  - Sumatriptan--a new treatment of migraine.

PMID- 8279162
TI  - Intravenous diltiazem hydrochloride rather than verapamil for resistant
      paroxysmal supraventricular tachycardia.

PMID- 8279163
TI  - Management of combative trauma patients.

PMID- 8279164
TI  - Improving emergency department response to victims of domestic violence.

PMID- 8279165
TI  - Conscious sedation in the emergency department.

PMID- 8279166
TI  - Whole-bowel irrigation in the management of ingested poisoning.

PMID- 8279167
TI  - Diagnosing acute cardiac ischemia.

PMID- 8279168
TI  - Prehospital 'do-not-resuscitate' orders--a new option.

PMID- 8279169
TI  - Bilateral Bell's palsy and aseptic meningitis in a patient with acute human
      immunodeficiency virus seroconversion.

PMID- 8279170
TI  - Recurrent angioedema and urticaria.
AB  - The case reported here illustrates the life-threatening aspects of angioedema and
      the need to thoroughly investigate the possible causes of this clinical finding.
      As discussed, the causes of angioedema are numerous. Commonly implicated in drug
      induced angioedema are antihypertensive ACE inhibitor drugs, as was originally
      thought with this patient. Because of her skin lesions and macrocytic anemia,
      further studies were done. These studies led to a diagnosis of hypocomplementemic
      urticarial vasculitis syndrome, an uncommon to rare form of acquired angioedema,
      urticarial vasculitis, arthritis, and obstructive airway disease associated with
      the production of autoantibodies to C1q. It is an autoimmune disorder related to
      but separate from SLE.

PMID- 8279171
TI  - Cross-cultural communication in the physician's office.
AB  - Physicians are increasingly called on to provide care for patients whose cultures
      differ from their own. I describe strategies, attitudes, and investigative
      methods that will enhance the experience of cross-cultural medicine for both
      patients and physicians.

PMID- 8279172
TI  - Integrity versus hypocrisy--that delicate balance. A commentary on humanity.

PMID- 8279173
TI  - Is peptic ulcer disease an infectious disease?

PMID- 8279174
TI  - 'Andropause'--are reduced androgen levels in aging men physiologically important?

PMID- 8279175
TI  - Lessons from hypersensitivity pneumonitis.

PMID- 8279176
TI  - Eosinophilic meningitis.

PMID- 8279177
TI  - Posthypnotic suggestion.

PMID- 8279178
TI  - AIDS in India.

PMID- 8279179
TI  - Gadolinium nonradioactivity.

PMID- 8279180
TI  - [Health promotion through development and improvement of organizational
      structure].
AB  - Postulates of work and organizational psychology describe criteria for human
      working conditions and the Ottawa-Charta of the World Health Organization depicts
      principles of health promotion. Based on these postulates and principles measures
      of corrective and preventive organizational design are presented. Deficiencies in
      health promotion are outlined derived by questionnaire data of employees and
      interview data of managers of Swiss companies in the service sector. An
      encouraging example of a successful introduction of semi-autonomous working
      groups in a Swiss bank shows the enhancement of health potentials by improving
      organizational structures.

PMID- 8279181
TI  - [Integrated health promotion in business: starting problems and proposed
      solutions].
AB  - Integrated worksite health promotion takes into account as well the demands of
      employees as those of the enterprises and at the same time applies to both,
      health behaviour and operational conditions of the companies. It is not
      restricted to a singular action but makes a continuous effort to promote the
      health of employees as an integrated part of employers' planning and politics.
      Apprehension between employers and employees seems to be one of the key obstacles
      of worksite health promotion. Therefore both sides have to keep negotiating to
      what extent health promotion has to improve efficiency of employees in respect to
      enterprises or how far operational conditions have to be adjusted to suit the
      well-being of personnel. A possible solution to solve this dilemma would be a
      widening of the conception of efficiency and incorporating of long-term thinking.

PMID- 8279182
TI  - [The role of ergonomics in the prevention of work-related diseases].
AB  - Processes linking individual situations and behaviours, as disclosed by the
      ergonomic analysis of job, to populations' epidemiological characteristics are
      discussed here. Epidemiology proposes deterministic models of general
      significance, reflecting stable phenomenons within wide populations. Ergonomics
      proposes cybernetic (or systemic) models of time- and space-limited significance,
      reflecting the variety of adapting and assimilating behaviours in homogeneous
      groups of workers. Regarding prevention, both approaches complement one another.

PMID- 8279183
TI  - [Occupation-specific indicators for strategic prevention in risk groups].
AB  - Using graphical representations to compare undistorted information it was
      attempted to bridge the gap between medicine and concerned risk-groups. Age
      standardized mortality rates in 1979-1983 for 55 occupational groups (in 11
      categories) of males aged 35 to 74 years were computed and compared to the Swiss
      national average; simultaneously the quantitative importance and the total
      mortality without accidents is shown for each occupational group: as an example
      the figure for lung cancer is reproduced. The elevated total mortality in the
      upper tertile of occupational groups is significantly explained by an increased
      risk of dying from circulatory or respiratory diseases, liver cirrhosis or
      malignancies of the lung, oropharynx, oesophagus or stomach. Foreseeable decrease
      of high-risk occupational groups will result in a further decline in mortality
      due to stomach cancer and cerebrovascular diseases in Switzerland.

PMID- 8279184
TI  - [Effect of occupation on health behavior and biological cardiovascular risk
      factors].
AB  - Within the framework of the second survey of MONICA-Switzerland (cantons of Vaud
      and Fribourg; canton of Tessin), the data of 683 working men were analysed to
      examine the relation between occupation and cardiovascular risk factors. For this
      purpose, lifestyle factors (smoking, nutritional habits, physical activity,
      alcohol intake) as well as blood pressure and serum lipoprotein concentrations
      were compared among 17 different occupational groups. Furthermore, every
      occupational group was ranked, based on the medians of the mentioned dependent
      variables. A strong relationship between socioeconomic status (recorded as number
      of years of schooling completed) and an index for healthy lifestyle was found.
      However, in some occupational groups a major discrepancy between socioeconomic
      status respectively lifestyle and measured cardiovascular risk factors (blood
      pressure, lipoprotein concentrations) was observed. It is therefore hypothesized
      that unknown occupational factors adversely affect blood pressure and serum
      lipoproteins for example in physicians, managers and executives whereas the
      contrary--beneficial effect of unknown occupational factors--is true for example
      for drivers and bricklayers.

PMID- 8279185
TI  - [Significance of life style factors for the blood lipids profile in bank
      employees].
AB  - In a study sample of 75 sedentary, non-smoking male bank employees (mean age 41.2
      +/- 7.8 years) the relationship between lifestyle characteristics and serum lipid
      concentrations were examined. According to the mortality statistics of the canton
      of Zurich, this population is at increased risk for coronary heart disease.
      Statistical analyses confirmed the predictive character of physical activity for
      serum lipid levels. A low level of physical activity was associated with
      significantly higher concentrations of apolipoprotein B and LDL-C (Pearson
      coefficient of correlation r = -0.38, p < 0.001 and r = -0.35, p < 0.01,
      respectively). Accumulation of upper body fat (estimated by the waist to hip
      ratio) revealed to be a better predictor of lipid levels than body mass index and
      showed highly significant positive correlations with atherogenic lipid fractions.
      The most pronounced differences were seen for triglyceride levels, where the
      subgroup of subjects in the lowest tertile of waist-hip ratio showed about 40%
      lower triglyceride values compared to the highest waist-hip ratio tertile. In a
      study population of self-selected, non-smoking men, high levels of LDL-C and
      apolipoprotein B could partially be explained by unfavourable life style
      characteristics, particularly physical inactivity. The waist-hip ratio,
      characterizing abdominal fat accumulation, proved to be a good indicator of an
      atherogenic lipid profile. Measuring waist-hip ratio in medical routine
      examinations should thus be considered.

PMID- 8279186
TI  - [Occupational exposure to isocyanates and individual susceptibility].
AB  - Patients with organic diisocyanate-induced pulmonary disease may be specially
      susceptible to the toxic effects of agent. Among 11 cases diagnosed in one year,
      the majority (10/11) were slow acetylators. The same patients were different from
      the control population in terms of alpha-1-antitrypsin phenotypes. Heterozygous
      combinations were more frequent than among controls. It seems that the
      combination of low N-acetylation capacity and a heterozygous alpha-1-antitrypsin
      predisposes to the disease.

PMID- 8279187
TI  - [Occupational asthma due to isocyanates: current research orientation in
      occupational hygiene].
AB  - The replacement of the HDI monomer by less volatile prepolymers is not
      accompanied by a decrease of the incidence of occupational asthma in Switzerland.
      Field measurements show that the prepolymer concentration levels may be high
      although the monomer is hardly detectable or complies with the norm. Our
      researches are focused on the improvement of generation and measurement
      techniques (international quality control), on the characterization of the
      prepolymers to study their transformation in biological media. Field surveys will
      be conducted to establish the prepolymer concentration profiles. We recommend for
      the introduction in Switzerland of threshold limit values for HDI-biuret and
      isocyanurate.

PMID- 8279188
TI  - [Psychological stress caused by work: burnout syndrome].
AB  - In a variety of helping professions emotional stress can lead to "burnout". The
      syndrome is characterised by emotional exhaustion, attitudinal hardening (loss of
      empathy) and a sense of decreased accomplishment. Longterm consequences of
      burnout can be mental problems such as depression or psychosomatic disorders.
      Affected employees are less productive and sick more often. They may even quit
      their jobs or need early retirement. In spite of this considerable loss of
      working force often neither those affected nor the employers are aware of the
      problem in time. Burnout seems to be caused by disproportionally high efforts
      (time, emotional involvement, empathy) and poor satisfaction (negative outcome)
      in addition to stressful working conditions (high demands). It affects mainly
      nurses, physicians, social workers, teachers and other similar professions. In
      order to prevent burnout, awareness of the problem must be promoted. Examples of
      job-specific measures for nurses and teachers are given. Their goal is to lower
      the professional stress and improve satisfaction. Social support and improved
      team cooperation can further protect against burnout.

PMID- 8279189
TI  - [Occupational risk: a sampling study in French-speaking Switzerland].
AB  - To prevent professional injuries and diseases, the need of analyzing risks at the
      work place from the individual as well as from collective point of view, is
      emphasized by law-makers. The present study shows that, using epidemiology
      enquiries allows one to analyse the prevalence of professional diseases in a
      population, without using the "LAA type" lists. One can see that these diseases,
      though linked to professional activity, go far beyond the limits of the insurance
      prescribed definitions.

PMID- 8279190
TI  - [Alcohol, occupational accidents and their sequelae].
AB  - Alcohol is a considerably more important risk factor for non occupational
      accidents than for occupational accidents, but somatic and psychosocial
      consequences of chronic alcohol consumption can also have very negative
      influences on the course of healing and professional rehabilitation. Three cases
      illustrate the importance of the primary and secondary prevention. They did
      charge the workers' compensation account of the companies involved with more than
      one million francs, with corresponding increases in workers' compensation
      premiums.

PMID- 8279191
TI  - [Cancer mortality according to occupation: implications for prevention].
AB  - The implications for the prevention of cancer and for health promotion at work is
      illustrated with two examples from an analysis of cancer mortality by occupation
      of Swiss men, 1979-1982. The classical approach of industrial medicine to the
      reduction of pollutants via legislative, technical and informative measures is
      applied in the case of sinonasal carcinoma and pleural mesothelioma that is
      increased with furniture-makers. The fact that a comparable cancer mortality
      pattern linked to miscellaneous factors like smoking, asbestos, cement dust,
      alcohol, chemicals, nutrition etc. is observed for the various jobs of the
      building industry, requires an extensive health promotion effort uniting
      industrial medicine with organizational and individual approaches.

PMID- 8279192
TI  - [Mass screening in occupational health from the practitioner's viewpoint].
AB  - A practicing occupational physician presents his view of meaningful prophylactic
      examinations. Requirements for these examinations are summarized in 7 postulates:
      that priority be given to primary prevention, to efficiency, and to medical and
      occupational history taking, that conclusions from these examinations always be
      transformed into concrete measures at the workplace, that continuing bilateral
      exchange of information with the supervising governmental authorities be assured,
      that synergistic effects be taken advantage of for the goals of general
      preventive medicine, and that the collected data be evaluated epidemiologically.

PMID- 8279193
TI  - [Impact of smoking regulations in the workplace].
AB  - Smoking control policies in the workplace may have several positive effects such
      as smoking cessation, nonsmoker protection, improvements in employee job
      satisfaction, etc. Indeed there may be some protest at first--as with most
      innovations! Yet numerous studies prove a very high support even by a
      considerable number of smoking employees, if the policy is appropriate
      implemented.

PMID- 8279194
TI  - [Biological monitoring in occupational medicine practice].
AB  - The following scheme proved to be a good tool carrying out biomonitoring studies
      for workers potentially exposed against chemicals: selection of substance of
      concern, literature survey, collection of workplace data, establishment of an
      "action level", laying down the monitoring strategy, biomonitoring study,
      evaluation of the results, documentation, information of the persons involved.
      The "action level" is useful to evaluate the biomonitoring results. It should be
      used as a guidance value at which the situation of exposure must be checked. The
      action level depends on legal threshold values and scientific findings in
      occupational medicine and toxicology. Furthermore the exposition minimum possible
      with current technology must be taken into consideration.

PMID- 8279195
TI  - [Air quality in offices: air supply remains an ignored parameter].

PMID- 8279196
TI  - [Health surveys in the plastering trade of the Basel region].
AB  - This health study was formulated for the plastering trade in the Basel region,
      which would be offered to all employees and included in their contracts. It
      covers the following points: Impaired mobility, especially back problems. Heart
      and circulation problems. General body fitness. It involves random testing of
      anonymous individuals and through a detailed study medical risk factors and early
      warning symptoms are established. Included in this preventive study is also
      information about the possible avoidance of damage to health and prevention of
      long term effects.

PMID- 8279197
TI  - [Health protection and health challenges in the workplace. Reports from a
      meeting, 22-23 October 1992, Zurich].

PMID- 8279198
TI  - [Meeting report health protection and health challenges in the workplace].

PMID- 8279199
TI  - [Health, health-related behavior and gainful employment].
AB  - Based on data collected in a survey as part of the Swiss Intercantonal Health
      Indicators Project (random sample stratified by age of 20-75 year old persons, n
      = 2106) relationships between level of employment (full, part-time, none) and
      health/disease as well as health behaviour were studied. Employed men and to some
      extent employed women as well were found to be less frequently sick and to feel
      more frequently well than non-employed men and women. Overall employment appears
      to affect health/disease in men more strongly than in women, whereas influence on
      health behaviour appears to be similar in both gender groups. The results of the
      study are discussed both with regard to further hypotheses of health research and
      opportunities of health promotion.

PMID- 8279200
TI  - [Health problems related to occupational activities].
AB  - Statistical data obtained from insurance companies give certainly a good picture
      of work effects on health in the field of accidents. This is different for
      occupational diseases, which are more difficult to diagnose and which are
      recognized on the basis of medicolegal criteria. Statistics do not involve other
      aspects than diseases, such as discomfort, ergonomical questions,
      psychophysiological consequences and situations where there is a limited role of
      occupation. Prevention of work related health problems has to consider these
      characteristics and needs to be based on risk analysis, a prospective procedure.
      The advantage of such an approach is the possibility of adjustment to a changing
      work environment and to new technologies.

PMID- 8279201
TI  - [Working conditions and health status from the workers' viewpoint].
AB  - In the present study details about disruptive factors in working conditions,
      elements injurious to health or general well-being, personal attitudes to work
      etc. have been obtained by means of a representative survey of about 2000
      employed persons in Switzerland. The most frequent disruptive factors in working
      conditions (> 30%) are noise and too little time for family and friends. A
      relatively large number of employed persons (20-25%) complain about
      unsatisfactory ventilation, air pollution due to dust, smoke etc., draughts,
      uncomfortable temperature, dry air, lifting and carrying heavy weights,
      uncomfortable body positions at work, unsuitable working hours, as well as
      pressure on time, too much concentration required, pressure of responsibility,
      insufficient recognition and lack of information about the planning and results
      of work being done. In the field of health complaints, back problems and nervous
      tension are at the top of the list (39%), followed by fatigue, sleeping problems,
      neck or leg problems, burning eyes, and stomach and intestinal problems (25-34%).
      The analysis shows that interrelationships exist--sometimes in the sense of a
      vicious circle--between complaints about disruptive factors in work conditions,
      professional groups, health problems and attitudes to professional live. The
      results provide a comprehensive survey of the incidence of problems in the fields
      of worker protection.

PMID- 8279202
TI  - [Addiction problems in the occupational environment].
AB  - The article discusses the context of a topic currently very much under discussion
      in Switzerland. It provides reflections on the concept of "addiction"--better
      replaced by "dependence syndrome"--and summarizes the few research results
      concerning the Swiss situation. Due to the lack of basic epidemiological data the
      prevalence of "dependence-related" problems at the work place and the actual
      consequences and costs of substance abuse can only be estimated. In a society
      with rapidly changing working conditions and requirements the common stereotypes
      of "alcohol-prone" occupations need a critical revision. Theoretical hypotheses
      are most advanced in the area of substance abuse in relationship to work-related
      stress coping.

PMID- 8279203
TI  - [Significance of psychological stress, absence of stress and resources for health
      promotion at the workplace].
AB  - Stress is defined as a lasting, averse situation, the avoidance of which appears
      to be subjectively important and where the individual is not sure of having
      enough ability to control it. Eustress, contrary to this, is characterized by the
      individual's confidence of being able to master given demands successfully.
      Therefore eustress can not equated with stress. One may assume that the repeated
      experience of mastering given demands constitutes a resource in coping with
      stressors. Empirical findings have shown psychic stressors to be systematically
      linked with individual discomfort preceding clinical symptoms. Therefore
      alterations to psychic stressors may be a mean of prophylaxis. Data from surveys
      on blue-collar workers moreover have suggested that two working conditions
      themselves may provide resources for coping with stressors: decision latitude and
      social support. Hence enlarging decision latitude and enhancing social support
      may be possibilities for prevention, especially in such cases, where stressors
      cannot (yet) be directly changed.

PMID- 8279205
TI  - The relationship between cycle stage and results of uterine culture in the mare.
AB  - A total of 368 uterine swabs were taken from mares in heat (n = 202) and from
      mares that were not in heat (n = 166). From 72 of the mares, two swabs were
      taken; one during either seasonal anoestrus or dioestrus, and one during oestrus.
      Swabs were taken during anoestrus/dioestrus in 94 other mares and during oestrus
      in the remaining 130 mares. Bacteriological cultures were done aerobically and
      classified as negative, insignificant or significant. There was a trend for more
      positive cytological specimens during oestrus than during anoestrus/dioestrus.
      The proportions of significant cultures were 12 of 202 (5.9%) in oestrous mares
      and 14 of 166 (8.4%) in anoestrous/dioestrus mares. Generally more insignificant
      than negative cultures were obtained during oestrus compared to
      anoestrus/dioestrus. Seven of 27 cultures that were classified as significant
      were associated with positive cytological specimens, and only 2 of 16 specimens
      that yielded pure cultures of E. coli contained neutrophils. Although the culture
      results did not differ significantly between the cycle stages, oestrus should be
      the preferred time for uterine examination.

PMID- 8279204
TI  - The effect of intensive flunixin treatment during the postpartum period in the
      bovine.
AB  - The aim of this study was to determine the effect of flunixin meglumine (FM), a
      substance which inhibits the prostaglandin biosynthesis, on the uterine
      involution. One of the characteristics of the postpartum period in cattle is the
      massive and extended release of prostaglandin (PG) F2 alpha. Eleven primiparous
      cows, divided into three groups, were included in the study. The first group was
      injected with FM four times daily, the second group twice daily and the third
      group acted as controls. The dose was 2.2 mg/kg body weight injected
      intramuscularly. The treatment period was 14 days beginning at parturition. Blood
      samples were collected prior to calving and up to 28 days postpartum. The plasma
      concentrations of the main circulating PGF2 alpha metabolite, i.e. 15-keto
      dihydro-PGF2 alpha, and progesterone were analysed. The involution of the uterus
      was assessed by rectal palpation and ultrasonography. The study showed that it
      was not possible to affect the time period to completed uterine involution, not
      even when a very intensive drug dosage was used. A statistical difference was
      found between the group receiving the most intensive treatment and the controls,
      when the areas under the prostaglandin metabolite curve (AUC) were compared. The
      PG synthesis and release were decreased by the treatment, but never totally
      suppressed. Even though the treatment with FM did not shorten the time to
      completed uterine involution, it was not detrimental for the process of
      involution. However, as the uterine involution is an inflammatory process,
      flunixin could, as an anti-inflammatory drug, be beneficial under certain
      circumstances.

PMID- 8279206
TI  - Trisomy 22 in a calf.
AB  - A case of trisomy 22 in a newborn calf is described. Previously, this anomaly has
      only been identified in one calf. The calf had several defects including
      brachygnathia superior, malformation of septum nasi and conchae, and an
      interventricular septal defect. Chromosome analysis was performed on cultured
      blood lymphocytes, and in all counted metaphases 61 chromosomes were present. The
      extra chromosome was identified as a chromosome 22 by R-banding.

PMID- 8279207
TI  - Isotopic water dilution technique in body fluid measurement in some domestic
      animal species.
AB  - Dilution procedures using tritiated water and Evans blue dye (T 1824) were
      applied to estimate total body water and plasma volume in small ruminants, pigs
      and cockerels during the two different seasons in Zimbabwe. The amounts of total
      body water (TBW) obtained were between 60% to 85% of the body weight in sheep and
      goats, 40% to 60% in pigs and 63% to 75% in cockerels. TBW values were
      significantly higher (P < 0.05) in the small ruminants than in pigs and observed
      age differences were significant (P < 0.05) in the small ruminants. There were
      significant (P < 0.05) seasonal differences in the total body water mean values
      but nonsignificant (P > 0.05) differences in the plasma volume mean values for
      the domestic species investigated.

PMID- 8279208
TI  - Biopotency of vitamin E in lucerne meal for chickens.
AB  - In order to estimate the biopotency of vitamin E in lucerne/alfalfa meal in
      comparison to that of dl-alpha-tocopheryl acetate (dl-alpha-Ta; all-rac-alpha-Ta)
      a study was conducted with newly hatched White Leghorn male chicks. An increase
      in the vitamin E level in the liver and plasma, and the prevention of nutritional
      encephalomalacia (NE) were used as criteria for biopotency. After a vitamin E
      depletion period of one week posthatching, the chicks continued on a
      semipurified, vitamin E free basal diet without vitamin E supplementation, or
      were repleted with graded levels of that vitamin for six weeks, provided as
      extracted lucerne oil or as dl-alpha-Ta. High performance liquid chromatography
      (HPLC) with fluorescence detection was used for the analysis of the vitamin E
      homologues. The diagnosis of NE was based on clinical and histopathological
      observations. A significant increase (P < 0.05) in vitamin E content in the liver
      and plasma was observed in response to dietary supplementation with both vitamin
      E sources. The linear increase both in the liver and plasma storage assays was
      associated with a reduced incidence of NE. The disease was totally prevented by a
      dietary supplement of 7.50 and 5.40 mg vitamin E/Kg feed provided as dl-alpha-Ta
      or lucerne oil, respectively. The natural biopotency of the vitamin E in lucerne
      meal compared with that of dl-alpha-Ta in the liver and plasma storage assays and
      in the prevention of NE was 123, 105 and 99%, respectively, as calculated by the
      slope ratio technique.

PMID- 8279209
TI  - Characterization of biliary proteins and composition of bile from sheep and
      goats.
AB  - Higher lipid content in gall bladder bile of sheep and goats as compared with
      monogastric species was due to higher proportion of glycerides. The volume of
      bile per gall bladder was higher in sheep than in goats. Bile from sheep and
      goats has a higher content of proteins and lower contents of dry matter,
      cholesterol and phospholipids compared with monogastric species. Biliary proteins
      partially purified by the ammonium sulfate precipitation method were
      characterized and quantified by polyacrylamide gel electrophoresis (PAGE), fast
      protein liquid chromatography (FPLC) and immunodiffusion. FPLC and PAGE profiles
      indicate that biliary proteins of sheep and goats are mainly of low mol. wt. of
      upto 65 KDa. Proportions of immunoglobulin (Ig) like molecules in biliary
      proteins precipitated by ammonium sulfate of different degrees of saturation,
      were 10.4 to 26.7 and 21.9 to 30.7 per cent of total proteins in bile of goats
      and sheep. IgG and IgA like molecules were the predominant Ig and lacked
      carbohydrates. On immunodiffusion such Ig like molecules did not show cross
      reactivity with humoral Ig. It was concluded that sheep and goats appear to
      secrete Ig into bile after deglycosylation and partial degradation. The proteins
      of smaller molecular weight may be secretory fragments or degradation products of
      Ig.

PMID- 8279210
TI  - Ionized calcium in calf serum: relation to total serum calcium, albumin, total
      protein and pH.
AB  - Serum ionized calcium, total calcium, albumin, total protein and pH were
      determined in 340 female Italian Friesian calves, aged from 1 day to 6 months.
      Analyses of data from calves divided into 7 age groups showed only occasional
      correlations between Ca++ and the other parameters. For pooled values for the
      calves aged 1-6 months, there were significant positive correlations between
      ionized and total calcium and between total calcium and albumin, and a negative
      correlation between ionized calcium and serum pH. However, the correlation
      coefficients were too low to be usable for prediction of the levels of ionized
      calcium from the levels of total calcium or from the other parameters. When it is
      essential to evaluate the calcium status of a calf, direct measurement of ionized
      calcium must be done.

PMID- 8279211
TI  - A caesarean section model to characterize coagulation in the fetal and uterine
      circulation during late gestation in dairy cattle.
AB  - A study was conducted to measure a coagulation profile including prothrombin time
      (PT), activated partial thromboplastin time (APTT), thrombin time (TT),
      fibrinogen concentration (FIB), and plasminogen activity (PLA) in the jugular
      vein, umbilical vein and artery and uterine vein of 18 Holstein Friesian cows
      during late gestation. A caesarean section was performed on all cows before term
      in order to obtain blood samples from the different sources and to deliver the
      calves. Blood plasma obtained from the umbilical vein and artery had a longer
      prothrombin time but shorter activated partial thromboplastin time and lower
      concentrations of fibrinogen and plasminogen than peripheral blood plasma.
      Thrombin time was similar throughout all blood vessels. No significant
      differences existed between the two samples drawn from the jugular vein before
      and during surgery. Highest coefficients of correlation were found between blood
      samples drawn simultaneously from the jugular and uterine vein (R2 = 41 to 96%).

PMID- 8279212
TI  - Effects of selenium status on bovine mononuclear cell function.
AB  - The effects of selenium (Se) status on the distribution and functional
      capabilities of bovine peripheral blood mononuclear cells (PBMC) were examined.
      No differences in proliferative responses to mitogens, interleukin (IL)-2
      production, IL-2 receptor expression, or lymphocyte trafficking patterns were
      observed between PBMC from dairy cows maintained on Se adequate or Se deficient
      diets. In contrast, Se deficiency significantly reduced the numbers of
      circulating monocytes when compared to cows fed a Se adequate diet. Differences
      in the number of circulating monocytes had no apparent effect on the accessary
      functions of these cells with respect to antigen presentation and IL-2
      production. These results suggest that the effect of Se-modified diets on bovine
      defense mechanisms is not mediated by the ability of peripheral blood lymphocytes
      to respond to antigen and mature into immunocompetent cells.

PMID- 8279213
TI  - Applicability of the critical difference.
AB  - The present study is concerned with the critical difference, which may help to
      judge whether or not the difference between two consecutive measurements with a
      certain probability (i.e. 95 percent) may be ascribed to natural variation.
      Knowledge of the applicability of the critical difference in veterinary medicine
      is sparse and therefore, to justify future use of the critical difference, it is
      important to know whether or not the critical difference performs as expected.
      The hypothesis to be tested in this study was that at least 95 percent of the
      differences between consecutive measurements, that have been obtained in animals
      where the component measured is known to be unchanged, should be within the
      critical difference. From previous studies it was known that a low-sodium diet
      had no influence on the plasma potassium concentration. The critical difference
      of the plasma potassium concentration in dogs was calculated as 0.5 mmol/l. using
      weekly measurements of this plasma component in a group of twenty healthy dogs.
      To test the hypothesis, this value was compared to the differences between
      consecutive weekly measurements of this plasma component in another group of
      eight dogs fed a low-sodium diet for five weeks. In agreement with previous
      studies, the plasma potassium concentration in the eight dogs did not change
      significantly during the feeding experiment. Of the fourty differences between
      consecutive weekly measurements, thirty-six were within the critical difference.
      This number was not different from the number expected from the hypothesis and
      thus, the critical difference performed as expected.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8279214
TI  - Response of sympatho-adrenal axis and adrenal cortex to short-term restraint
      stress in sheep.
AB  - The sympatho-adrenal and pituitary-adrenal cortex axes are the most sensitive,
      and specific indicators of stress in animals. Increased plasma levels of
      catecholamines and glucocorticoids are generally considered as the classical
      response to stress. Most experiments on immobilization have been performed on
      rats and only a few of them concerned domestic animals. In this experiment we
      want to learn whether short-term restraint-a stressor most commonly used in
      animal husbandry-is a stressor for sheep (ewes) like in rats. For this reason we
      measured adrenaline (A), noradrenaline (NA) (radioenzymatic method), cortisol
      (RIA method), glucose and free fatty acids (FFA). Unlike in rats, in stressed
      sheep the peak of A appeared earlier than the NA peak, i.e. at 2 and 5 min. of
      stress, respectively. In contrast to rats, the basal and stress levels of NA
      exceeded the corresponding level of A. Cortisol concentration rose 7 fold above
      baseline and maximal concentration appeared at a time (15-30 min.) observed in
      other animal species. A similar time-related increase was observed in the plasma
      FFA concentration. It increased maximally 3.2 fold at 15 min. of stress. A
      significant correlation coefficient was found between plasma cortisol and FFA (r
      = 0.91) what may suggest the lipolytic effect of ACTH and/or a positive feedback
      of FFA on the hypophysis-adrenal axis. The plasma glucose of stressed animals
      rose only 1.47 fold above the basal level. A significant correlation was found
      between cortisol and glucose (r = 0.53) whereas no correlations have been
      obtained between A, NA and glucose or FFA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279215
TI  - Nephrolithiasis in Iranian sheep.
AB  - Out of 500 Iranian sheep examined, six revealed the presence of lithiasis in
      their kidneys. Nephroliths in three animals were composed of ammonium magnesium
      phosphates and in the others of calcium carbonates and calcium phosphates.
      Interestingly sodium and ammonium urate crystals were present in the kidneys of
      three animals.

PMID- 8279216
TI  - Non-surgical treatment of primary hyperparathyroidism.

PMID- 8279217
TI  - Acute change in parathyroid function in primary hyperparathyroidism following
      ultrasonically guided ethanol injection into solitary parathyroid adenomas.
AB  - Ultrasonically guided percutaneous injection of 96% ethanol into solitary
      parathyroid tumours in patients with primary hyperparathyroidism may be used as
      an alternative to surgery in selected patients. Contrary to surgical
      parathyroidectomy, the acute changes in parathyroid function following ultrasound
      guided chemical parathyroidectomy have never been described. Seven consecutive
      and highly selected patients with primary hyperparathyroidism were treated with
      ultrasonically guided injection of ethanol (96%) into solitary and biopsy
      verified parathyroid tumours. Basic treatment included a maximum of three
      injections separated by intervals of 24 h. In six of the seven patients normal
      serum values of ionized calcium were achieved within 36-120 h (median 36 h) and
      normal serum values of intact parathyroid hormone within 6-78 h (median 24 h).
      Three patients received two injections and three patients three injections. One
      patient remained hypercalcaemic in spite of three injections. Subsequent surgery
      showed the patient to have two parathyroid adenomas, of which only one had been
      detected ultrasonically. The present study has demonstrate a fast normalization
      of parathyroid function following two to three ethanol injections into solitary
      parathyroid tumors in selected patients with primary hyperparathyroidism.

PMID- 8279218
TI  - Results of ultrasonically guided percutaneous ethanol injection into parathyroid
      adenomas in primary hyperparathyroidism.
AB  - Surgery is the usual treatment for primary hyperparathyroidism. However, some
      patients with high surgical risks are not suitable for surgery. For such
      patients, we propose, as an alternative treatment, ultrasonically guided
      percutaneous ethanol injection into parathyroid adenomas, in order to induce
      necrosis of the tumor. We report, here, the results of ultrasonically guided
      percutaneous ethanol injection into parathyroid adenomas, during a prolonged
      follow-up period up to 49 months, in a group of 13 patients (median age 79 years)
      with primary hyperparathyroidism and contraindications for surgery. In seven
      patients, complete normalization of plasma calcium, phosphorus and parathyroid
      hormone (PTH) levels was achieved after ethanol injections, with no recurrence of
      hypercalcemia during a median follow-up period of 28 months (total success). In
      these seven patients, plasma calcium, phosphorus and PTH levels were normalized
      48 h after the successful ethanol injection. In four patients, a partial success
      was obtained with clinical improvement and normalization of plasma calcium levels
      but without complete normalization of plasma PTH levels. This partial success is
      due to incomplete necrosis of the adenoma, as has been confirmed in one patient
      by histopathological examination. The ethanol injection treatment failed in only
      two patients. This treatment was always well tolerated and no major side-effects
      were observed. In conclusion, our results give evidence that ultrasonically
      guided percutaneous ethanol injection into parathyroid adenomas can be a very
      useful alternative therapy in patients not suitable for surgery.

PMID- 8279219
TI  - Possible variation in bone resorption during the normal menstrual cycle.
AB  - In order to determine whether bone turnover varies during the normal menstrual
      cycle, we measured biochemical markers of bone resorption (serum pyridinoline
      cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting
      urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and
      fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma
      osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum
      alkaline phosphatase) in ten healthy premenopausal women every two or three days
      for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its
      nadir during the follicular phase and its peak during the luteal phase, and an
      overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic
      changes were observed in the urinary parameters of bone resorption or in the
      biochemical markers of bone formation. We conclude that sICTP, a new biochemical
      marker of bone resorption, undergoes small variations during a normal menstrual
      cycle in premenopausal women, whereas the biochemical markers of bone formation
      remain constant.

PMID- 8279220
TI  - Bone metabolism in obesity: changes related to severe overweight and dietary
      weight reduction.
AB  - A non-invasive evaluation of bone metabolism was performed in 44 morbidly obese
      patients before and after a mean weight loss of 22.4 kg (range 7.9-43.4 kg) after
      2 months and a further weight loss of 7.3 kg after 8 months (0.8-20.0 kg). This
      weight reduction was obtained by a nutritionally adequate very-low-calorie diet.
      Before treatment the bone mineral content of the distal forearm was increased
      compared to normals (51.9 U vs. 43.7 U, p < 0.001). Bone formation was evaluated
      by serum alkaline phosphatase and serum osteocalcin. Serum alkaline phosphatase
      was increased (187.8 U/l vs 147.4 U/l, p < 0.001) while serum osteocalcin was
      lower than in the controls (0.67 nmol/l vs 0.98 nmol/l, p < 0.01). Bone
      resorption, as measured by the urinary hydroxyproline/creatinine ratio, was not
      increased in the obese patients (19.2 molar ratio x 10(-3) vs 16.7 molar ratio x
      10(-3), NS). After 2 months, the bone mineral content had declined by 3.3%. Serum
      alkaline phosphatase remained unchanged (187.8 U/l vs 186.9 U/l, NS) but serum
      osteocalcin demonstrated a significant rise (3.94 nmol/l vs 10.53 nmol/l, p <
      0.001), parallel to changes in the hydroxyproline/creatinine ratio (19.2 molar
      ratio x 10(-3) vs 25.2 molar ratio x 10(-3), p < 0.001). At 8 months, no further
      change in the bone mineral content was seen. The hydroxyproline/creatinine ratio
      did still increase (from 25.8 molar ratio x 10(-3) to 30.1 molar ratio x 10(-3),
      p < 0.05), while serum alkaline phosphatase and serum osteocalcin remained
      unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279221
TI  - Urinary growth hormone excretion in acromegaly: diagnostic value in mild disease
      activity.
AB  - The biochemical assessment of disease activity in acromegaly still presents a
      problem, especially in treated patients with mild clinical symptoms. We therefore
      examined the diagnostic value of the measurement of urinary growth hormone (GH)
      excretion in seventy unselected patients with acromegaly of different activity by
      comparing it to serum GH, serum insulin-like growth factor I (IGF-I) and clinical
      activity. There were highly significant, positive correlations between urinary GH
      and serum GH, serum IGF-I as well as clinical activity score (p < 0.00005),
      although some overlap between the groups was observed. In seven patients with low
      serum GH values (< 2.0 micrograms/l) discordant results were found. Two of the
      seven patients were clinically mildly active, but only IGF-I was either elevated
      or within the upper normal range; in three other patients who appeared clinically
      cured either IGF-I (N = 1) or urinary GH (n = 2) alone were increased. In the
      remaining two patients elevated serum IGF-I and urinary GH as well as activity
      score suggested disease activity. Thus, in the majority of cases, urinary GH was
      significantly correlated to the other three parameters, but added little
      information to that obtained by serum IGF-I. In conclusion, urinary GH
      measurements in difficult cases may provide a more direct information on the GH
      status than IGF-I.

PMID- 8279222
TI  - Differences in serum insulin-like growth factor I and sex-hormone-binding
      globulin levels between late and early prepuberty in patients with idiopathic and
      organic growth hormone deficiency.
AB  - It has been reported that growth hormone modulates serum levels of insulin-like
      growth factor I (IGF-I) positively and serum levels of sex-hormone-binding
      globulin (SHBG) negatively. We have measured IGF-I and SHBG concentrations in 24
      prepubertal patients with growth hormone deficiency. Twelve of these patients had
      had intracranial tumors removed (organic growth hormone deficiency) and 12 had
      growth hormone deficiency of unknown etiology (idiopathic). Fifty-two prepubertal
      control subjects, admitted for elective surgery, were also studied. All
      prepubertal patients were divided into two age groups: older and younger than 7
      years of age. In both groups there were patients with multiple pituitary
      deficiencies on hydrocortisone and/or levothyroxine sodium replacement therapy.
      In the age group younger than 7 years, serum IGF-I was not significantly
      different between organic and idiopathic growth hormone deficiency (0.28 +/- 0.21
      versus 0.062 +/- 0.071 mU/l) but serum SHBG levels were different (74.6 +/- 33.5
      versus 173 +/- 59 nmol/l, p < 0.05). These values were not significantly
      different from controls (0.47 +/- 0.25 mU/l and 132 +/- 47 nmol/l, respectively).
      In the age group older than 7 years, there was no significant difference between
      organic and idiopathic growth hormone deficiency in serum IGF-I (0.33 +/- 0.17
      versus 0.16 +/- 0.11 mU/l) or serum SHBG (113 +/- 72 versus 108 +/- 17 nmol/l).
      These values were significantly different from controls (1.04 +/- 0.36 mU/l and
      68.7 +/- 31.7 nmol/l, p < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279223
TI  - Growth hormone-releasing activity of growth hormone-releasing peptide-1 (a
      synthetic heptapeptide) in children and adolescents.
AB  - The heptapeptide growth hormone-releasing peptide-1 (GHRP-1), one of a series of
      recently synthesized small growth hormone (GH)-releasing peptides, was
      administered as an iv bolus (1 microgram/kg) to 15 (six prepubertal, nine
      pubertal) short but healthy children and adolescents and to eight juvenile
      patients with pituitary insufficiency (four with isolated growth hormone
      deficiency, two with multiple pituitary hormone deficiencies, one with partial GH
      deficiency and one with GH-releasing hormone (GHRH) deficiency). Eleven out of 23
      subjects also underwent an in GHRH (1-29) test (1 microgram/kg). All the healthy
      children responded with a progressive rise in plasma human GH (hGH) peaking at 15
      30 min, with a significantly higher rise (p < 0.05) in the pubertal than
      prepubertal group. The hGH response to GHRH (1-29) in these children was similar
      or slightly higher. Six hypopituitary patients had no response to either GHRP-1
      or GHRH; the patient with partial GH deficiency had a hGH peak of 6.5
      micrograms/l (at 5 min) to GHRP-1 and 9.2 micrograms/l (at 15 min) to GHRH. One
      patient had no response of hGH to hypoglycemia, clonidine and GHRP-1, but the
      plasma hGH rose to 10 micrograms/l after GHRH. Following the GHRP-1 bolus there
      was a significant (p < 0.01) rise in plasma free thyroxine and a decrease of
      thyrotropin (p < 0.01), both in the limits of normal values. There was also a
      transitory rise of plasma cortisol (p < 0.05). Plasma prolactin, luteinizing
      hormone and follicle-stimulating hormone did not change.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8279224
TI  - Acute and chronic hyperbaric oxygen exposure in humans: effects on blood
      polyamines, adrenocorticotropin and beta-endorphin.
AB  - Plasma beta-endorphin, adrenocorticotropin (ACTH) and blood polyamine (spermidine
      and spermine) concentrations were evaluated in healthy adult male athletes
      undergoing hyperbaric oxygen exposure for 10 days (2.8 atm, 100% O2, 60 min
      daily). In the "acute phase", corresponding to the first day of treatment, and in
      the "acute in the chronic phase", corresponding to the values obtained on the 5th
      and 10th days after 60 min of hyperbaric O2, both ACTH and beta-endorphin levels
      increased significantly, whereas no variations were observed for polyamine
      concentrations. In the "chronic phase", corresponding to the basal values of the
      5th and 10th days of treatment, we found a different pattern. In fact, the
      concentration of polyamines showed a remarkable enhancement, while ACTH and beta
      endorphin levels remained unchanged. No significant variations were observed
      during hyperbarism with air. These results demonstrate different modifications of
      polyamines and beta-endorphin and ACTH in subjects submitted to hyperbaric oxygen
      exposure.

PMID- 8279225
TI  - Light deprivation increases plasma levels of melatonin during the first 72 h of
      life in human infants.
AB  - The development of rhythmic melatonin secretion in full-term neonates seems to
      occur at about 12 weeks of age, but activity of the pineal gland from 1 to 12
      weeks of age is not well documented. To determine whether the pineal gland
      actively secretes melatonin and reacts to photoperiodic information during this
      period, we analyzed 45 full-term infants exposed to continuous artificial light
      during 24, 48 and 72 h after birth for treatment of hyperbilirubinemia. During
      this light treatment, the eyes of the neonates were completely covered to avoid
      damage, thus the infants were under continuous light deprivation. Phototherapy
      significantly decreased plasma bilirubin during treatment. With regard to pineal
      gland activity, the shortest period of light deprivation tested, 24 h,
      significantly increased plasma melatonin levels from 152.66 +/- 11.57 to 244.86
      +/- 19.49 ng/l (mean +/- SEM; p < 0.001). The other periods tested, 48 and 72 h
      of light deprivation, led to similar percentages of melatonin stimulation. These
      results suggest that the pineal gland of neonates, before displaying rhythmic
      metabolic activity, is sensitive to changes in environmental illumination,
      indicating maturity of some features of suprachiasmatic nuclei function.

PMID- 8279226
TI  - Effects of bovine growth hormone (GH) expression in transgenic mice on serum and
      pituitary immunoreactive mouse GH levels and pituitary GH-releasing factor
      binding sites.
AB  - Pituitary and serum levels of homologous growth hormone (GH) and characteristics
      of specific GH-releasing factor (GHRF) binding to pituitary homogenates were
      examined in transgenic mice expressing bovine GH (bGH) gene regulated by
      different promoters [mouse metallothionein-I (MT) or phosphoenolpyruvate
      carboxykinase (PEPCK)] and in their normal littermates. Pituitary GH
      concentration and GHRF binding were reduced by approximately 50% in transgenic MT
      bGH mice in which serum bGH levels were about 20 micrograms/l and by
      approximately 95% in transgenic PEPCK-bGH mice in which serum bGH levels were
      tenfold higher. Suppression of plasma immunoreactive mouse GH (mGH) levels was
      detected in MT-bGH but not in PEPCK-bGH animals, presumably due to cross-reaction
      of the antiserum employed with bGH. Scatchard plots of GHRF binding to washed
      homogenates of pituitary glands from normal and young adult MT-bGH transgenic
      mice were curvilinear, indicating the presence of two types of binding sites,
      with low and high affinities. Both types of binding sites were reduced in number
      in MT-bGH transgenic mice without changes in their affinity. In 5-7-month-old MT
      bGH transgenic mice there were changes in pituitary GH levels, in GHRF binding
      levels and in characteristics of GHRF binding that closely resembled the
      alterations described previously in aging rats. We conclude that over-expression
      of heterologous GH genes in transgenic mice can lead to partial or virtually
      complete suppression of somatotroph function, depending on the levels of
      heterologous GH in the circulation, and that transgenic MT-bGH mice exhibit
      symptoms of remarkably early onset of neuroendocrine aging.

PMID- 8279227
TI  - Effects of 2-buten-4-olide, an endogenous feeding suppressant, on the pulsatile
      secretion of luteinizing hormone in ovariectomized rats.
AB  - The effects of 2-buten-4-olide (2-B40), an endogenous feeding suppressant, on the
      secretion of luteinizing hormone (LH) were studied in ovariectomized rats.
      Intraperitoneal (ip) administration of 2-B40: adult female ovariectomized Wistar
      rats were given daily ip injections of solution containing 2-B40 at 0, 50 or 100
      mg/kg body wt for 14 days. This ip treatment with 2-B40 significantly decreased
      the mean LH concentration and pulse frequency of LH. Intravenous (iv)
      administration of 2-B40: a solution of 2-B40 (50 or 100 mg/kg body wt) was slowly
      injected through an intra-atrium catheter and blood samples were taken every 6
      min for 2 h. This iv treatment significantly suppressed the LH pulse frequency
      but had no significant effect on the LH amplitude or mean LH. Injection of 2-B40
      into the third cerebroventricle: the injection of 2-B40 into the third
      cerebroventricle of freely moving rats decreased the mean LH concentration and
      the frequency and amplitude of LH pulses. Third cerebroventricle injection of a
      corticotropin-releasing factor (CRF) receptor antagonist before third
      cerebroventricle injection of 2-B40: the specific CRF receptor antagonist alpha
      helical-CRF (9-41) was injected into the third cerebroventricle of ovariectomized
      rats before injection of 2-B40. Administration of 2-B40 into the third
      cerebroventricle significantly decreased the mean LH, concentration and pulse
      frequency. Third cerebroventricle injection of the CRF antagonist at 50
      micrograms/rat and then 2-B40 also resulted in significant suppression of the
      mean LH concentration and pulse frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279229
TI  - Heterogeneous Dolichos biflorus lectin binding to a subset of rat alveolar
      macrophages in normal and fibrotic lung tissue.
AB  - The distribution of Dolichos biflorus lectin in the rat lung and during fibrosis
      after irradiation was investigated by lectin histochemical and electron
      microscopical techniques and double immunofluorescence labelling with the
      monoclonal antibodies RM-1 and ED-1. The results indicate a selective reaction of
      Dolichos biflorus lectin with a subpopulation of alveolar macrophages. No binding
      of the lectin was detectable in ED-1-positive macrophages but strong staining
      occurred in a part of the RM-1-positive cell population. In fibrotic lung
      specimens an increased number of Dolichos biflorus lectin-positive macrophages
      was found in which focally ED-1 reactive and RM-1 negative cells appeared. The
      finding of changing lectin binding pattern in a radiation-induced lung model
      emphasizes the suitability of the Dolichos biflorus lectin as a marker of
      macrophage activation or functional specialization.

PMID- 8279228
TI  - Brain area specific differences in the effects of neuroactive steroids on the
      GABAA receptor complexes following acute treatment with anaesthetically active
      steroids.
AB  - Regional differences in the effects of neuroactive steroids on the GABAA receptor
      complex have been demonstrated in vitro (1-3). In order to elucidate if a
      regionally different modulation of the GABA-binding site also occurs after acute
      steroidal treatment, in the present study the effects of systemically applied
      progesterone (10 mg/kg body wt) and its metabolite 3 alpha-hydroxy-5 alpha
      pregnane-20-one (3 alpha, 5 alpha-THP) (2 mg/kg body wt) on the specific
      [3H]muscimol binding to the GABA-binding site was evaluated using membrane
      fractions prepared from five different brain areas of ovariectomized rats. The
      receptor density (mumol/kg protein) was not affected in all brain areas
      investigated by treatment with 3 alpha, 5 alpha-THP but was enhanced selectively
      in the frontal cortex and hippocampus of progesterone-treated animals. A decrease
      of affinity was observed in medulla after application of progesterone or 3 alpha,
      5 alpha-THP, in contrast to the hypothalamus, which was the single region
      exhibiting an increase of affinity after steroidal administration. In the frontal
      cortex and hippocampus only the injection of progesterone reduced the affinity,
      whereas in cerebellum both steroidal treatments were incapable of affecting the
      affinity. These regional differences in response to the GABA-binding site to
      acutely applied progesterone and 3 alpha, 5 alpha-THP are consistent with the
      existence of heterogeneous populations of GABAA receptor-coupled steroid-binding
      sites.

PMID- 8279230
TI  - Chronoimmunohistochemical localization of epidermal growth factor in the
      submandibular gland of male rats.
AB  - Chronobiological oscillation was established for epidermal growth factor (r-EGF)
      in granular convoluted tubule (GCT) cells of the male rat submandibular gland
      (SMG) using immunohistochemistry. The high amplitude oscillation with a peak at 9
      p.m. and low amplitude oscillation during the day time was noted. The
      distribution pattern of the r-EGF in the GCT segment was time-dependent, as it
      was seen at 3 p.m. when many cells with r-EGF staining were detectable. The
      higher reactivity during the activity phase of the rats may correlate with the
      intracellular biosynthesis of r-EGF required for cell proliferation and
      maintenance of ductal integrity. The chronobiological oscillation pattern of r
      EGF seems to be important for the maintenance of ductal integrity and wound
      healing.

PMID- 8279231
TI  - Histochemistry of the forestomach epithelium of the reindeer calf.
AB  - Samples from the rumen, reticulum and omasum of 26 reindeer calves were taken
      during the winter season. Non-specific alkaline and acid phosphatases, cytochrome
      and amine oxidases as well as succinate, lactate and 3-hydroxybutyrate
      dehydrogenases were demonstrated in the epithelium histochemically. The
      phosphatases were usually present in all the epithelial layers, whereas the
      activities of the other enzymes decreased in the outer layers and could not be
      demonstrated in the stratum corneum. The activity of alkaline phosphatase seemed
      to be highest in the reticulum and lowest in the omasum. The reason for the
      higher activity of this enzyme in epithelial taps in the rumen and omasum and in
      the reticular and omasal papillae may be the greater need for effective vertical
      transcellular transport in these regions. There was a tendency for enzymes other
      than phosphatases to be more active in the rumen than in the other forestomachs,
      which probably reflects the higher metabolic activity of the ruminal epithelium.
      No clear differences between early and late winter could be demonstrated.

PMID- 8279232
TI  - Immunohistochemical analysis of ras oncogene product p21 in human endometrial
      carcinoma.
AB  - Monoclonal antibody rp-28 directed against the ras gene product p21 has been used
      to evaluate ras p21 expression in endometrial lesions. Endometrial cancer showed
      a variable reactivity according to histological type: in well differentiated
      adenocarcinoma 63% were positive (12/19); in moderately differentiated
      adenocarcinoma 53% were positive (8/15); in poorly differentiated adenocarcinoma
      40% were positive (2/5). The staining intensity of ras p21 seemed to be stronger
      in the more differentiated types of endometrial carcinoma. In endometrial
      carcinoma with premenopausal women, 27% were positive (3/11), and with
      postmenopausal women 71% were positive (20/28). The difference between
      premenopausal and postmenopausal groups was statistically significant (Mantel
      Haenszel procedure, M-H chi 2 = 6.765, P < 0.01). The results suggest the
      existence of different carcinogenetic mechanisms in these two groups of
      endometrial cancer.

PMID- 8279233
TI  - Ultrastructural characteristics of zebrafish spinal motoneurons innervating
      glycolytic white, and oxidative red and intermediate muscle fibers.
AB  - Spinal motoneurons in the zebrafish were classified using morphological criteria.
      Dorsomedial white motoneurons which innervate the fast, glycolytic white muscle
      fiber compartment were distinguished from ventrolateral red and intermediate
      motoneurons which innervate the slow, oxidative, red and intermediate muscle
      fiber compartments. Synapses on cell somata and cell organelles were studied in
      detail. The motoneurons which innervate white muscle fibers (W motoneurons) are
      considerably larger than those which innervate red and intermediate muscle fibers
      (RI motoneurons; W > RI). Significant differences were also found in the size of
      the nucleus (W > RI) and in the ratio size nucleus/size soma (W < RI); small
      differences were found regarding endoplasmic reticulum (W > RI) and mitochondria
      (W < RI). There were no differences in synaptic apposition length or percentage
      of terminals with flat vesicles. Small differences were discerned with regard to
      covering percentages (W < RI) and percentage of terminals with round vesicles (W
      > RI). Terminals with dense cored vesicles appeared on W motoneuron somata only.
      Within the motoneuron population, there was a positive correlation between the
      coverage of terminals containing flat vesicles and the perimeter of the cell
      soma. In RI motoneurons, there was a positive correlation between the perimeter
      of the cell and the amount of endoplasmic reticulum. A negative correlation was
      found between the RI cell perimeter and mitochondria, which is in line with a
      high succinate dehydrogenase activity in small cells.

PMID- 8279234
TI  - Lectin binding studies with FITC-marked WGA and UEA I and flowcytometric
      measurements on isolated rat pancreatic acinar cells.
AB  - Lectin binding to the glycocalyx of isolated rat pancreatic acinar cells was
      studied by flowcytometric measurements. The pancreatic exocrine cells were
      prepared after collagenase digestion and cleaned in a density gradient. The
      fluorescence of cells was measured in a FACScan after binding of FITC marked WGA
      or UEA I. The binding of lectins was inhibited by preabsorption of WGA-FITC with
      N-acetyl-glucosamine, sialic acid or chitinous and by preabsorption of UEA-FITC
      with alpha-L-fucose, respectively. Furthermore, we were able to measure a
      decreased WGA-FITC and UEA-FITC binding after a short preincubation of isolated
      cells with the peptide hormone cholecystokinin and its agonists (caerulein,
      pentagastrin).

PMID- 8279235
TI  - Immunohistochemical detection of lactoferrin in different human glandular tissues
      with special reference to the exocrine pancreas.
AB  - The immunohistochemical detection of lactoferrin was carried out with the PAP
      technique on pancreatic tissue samples of 23 patients, operated for acute (13) or
      chronic (4) pancreatitis as well as for adenocarcinomas (6). In order to control
      our immunohistochemical technique and the antisera produced by us we studied some
      tissue samples of human mammary gland and parotis. We detected lactoferrin in the
      glands of parotis and mammae as well as of their secretions. In the pancreatic
      tissue we found a positive reaction only in granulocytes of inflammatory areas
      with the exception of a luminal reaction on the surface of acinar cells in one
      case of pancreatic adenocarcinoma. We would like to interpret our results with
      the hypothesis of granulocytic origin of immunochemically detectable lactoferrin
      in the pancreatic juice of patients, especially in cases of chronic pancreatitis.

PMID- 8279236
TI  - Demonstration of membrane-associated phospholipase A2 in cultivated heart muscle
      cells by immunogold-technique in surface replicas.
AB  - Recently we produced mAb's to phospholipase A2 (PIA2) from bee venom for
      different purposes (allergen-identification and -standardization). Obviously one
      of these monoclonal antibodies "5D5" binds to a conserved (cross reactive)
      epitope of membrane PIA2 of intact cells. In this study we demonstrate binding of
      5D5 to membrane associated phospholipase A2 of rat heart muscle cells by means of
      two-step immunogold technique in combination with replica technique.

PMID- 8279237
TI  - Relationship between naphthol AS-D chloroacetate esterase and prostaglandin
      synthase.
AB  - The close topographical correlation between naphthol AS-D chloroacetate esterase
      positive macrophages and prostaglandin synthase-rich macrophages in the thymus of
      normal and cyclosporin-treated rats was observed. It seems possible that
      chloroacetate esterase is an enzyme related to metabolism of arachidonic acid
      and/or production of its active metabolites.

PMID- 8279238
TI  - Tissue carriers for processing fragile bio-materials in immuno-electron
      microscopy.
AB  - The preparation and use of tissue carriers for processing fragile biological
      materials from postfixation up to embedding in electron microscopy is described.
      Trimmed small pieces of vibratome sections can be very practical and safely
      transported in these carriers throughout osmification, dehydration for long
      times, and infiltration up to embedding in epoxy resins. This small device is
      especially suited for post-embedding immunogold electron microscopy.

PMID- 8279239
TI  - A new technique for post-embedding immunogold localization of vasopressin in the
      rat median eminence.
AB  - A modified cryosubstitution method is described which simultaneously preserves
      the ultrastructure and antigenicity of the osmium-sensitive neuropeptide
      vasopressin in rat median eminences. The organs were aldehyde-fixed, osmicated,
      and embedded in Epon. Thin sections were no longer needed to be etched and the
      titer of primary antiserum was near to the light microscopic level. Furthermore
      ice crystallization could not be observed.

PMID- 8279240
TI  - Quantitative cytochemical study of some enzymatic activities in preovulatory
      bovine oocytes after in vitro maturation.
AB  - In the present study quantitative cytochemical assays were used to measure some
      enzymatic activities in situ in bovine meiotically immature oocytes and oocytes
      matured in vitro, since the special metabolic activity of the growing oocytes may
      be a pivotal factor in stabilizing the meiotically arrested oocytes.
      Modifications of this particular metabolism might destabilize the arrested
      meiosis. Preovulatory oocytes, mostly at the germinal vesicle stage, were
      obtained by puncturing follicles ranging from 2 to 6 mm in diameter with a
      hypodermic needle. A group of collected oocytes was incubated in maturation
      medium CRML 1066 to obtain metaphase II oocytes. Succinate, lactate and glucose-6
      phosphate dehydrogenase activities in just collected meiotically immature and in
      vitro matured oocytes were assayed cytochemically. Microdensitometric
      measurements were made with a Vickers M85a scanning microdensitometer. Our
      findings show that: 1) succinate dehydrogenase activity was significantly
      increased in matured oocytes; 2) lactate dehydrogenase activity was present and
      very strong in immature oocytes but was detectable in only about 50% of matured
      oocytes, with significantly lower integrated optical density values; 3) glucose-6
      phosphate dehydrogenase activity was very high in immature oocytes but
      significantly decreased after in vitro maturation; 4) there was no linear
      correlation between the integrated optical densities of the three enzymatic
      activities and the diameters of the oocytes. We suggest that the ability to
      utilize glucose may appear earlier in bovine oocytes than in other species and
      takes place at the time of maturation.

PMID- 8279241
TI  - Age-dependent changes of enzyme activities in the different fibre types of rat
      extensor digitorum longus and gastrocnemius muscles.
AB  - The age-dependent change of metabolic profiles of SO (slow-oxidative), FOG (fast
      oxidative glycolytic) and FG (fast-glycolytic) fibres of muscles digitorum longus
      and musculus gastrocnemius of rat from 14 days to 370 days was measured
      cytophotometrically. Fibres were classified visually and using cytophotometrical
      data from staining reactions for myofibrillar adenosinetriphosphatase (ATPase),
      succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (alpha
      GPDH) in the same fibre. The fibre type population as percentage was estimated at
      different ages. The age-dependent change of enzyme activities was demonstrated in
      each fibre type. SDH-heterogeneity of FOG-fibres and consequently an overlap with
      SO-fibres was detected. The alpha-GPDH/SDH-activity quotient allowed to
      distinguish SO-, FOG- and FG-fibres, and the age-dependent change of activity
      quotient characterized the change of metabolic properties in the concerned fibre
      types. Whereas in gastrocnemius muscle the metabolic profile of FOG-fibres was
      similar to that of SO-fibres, in extensor digitorum longus muscle the metabolism
      of FOG-fibres was similar to that of FG-fibres. Between the two muscles
      differences were also shown for the fibre type responsible for changes of enzyme
      activities in the whole muscle, measured biochemically.

PMID- 8279242
TI  - [A study on the management of accuracy by the close examination in the gastric
      mass survey].
AB  - To reduce mortality rate of gastric cancer by the gastric mass survey, the
      effectiveness of gastro-endoscopy was compared with the direct fluoro-radiography
      as the close examination. By means of the indirect fluoro-radiography, the
      gastric mass surveys was performed for 695, 703 subjects in the period of 6 years
      starting from 1985 April to 1991 March in the Kagoshima Prefecture. 327 gastric
      cancers (0.66%) out of 49,545 subjects were found by the direct fluoro
      radiography as the close examination, 261 gastric cancers (0.98%) out of 26,642
      subjects were found by the gastro-endoscopy as the close examination. Furthermore
      the gastro-endoscopy (detection rate: 2.5%) showed higher efficiency and
      effectiveness than the direct fluoro-radiography (detection rate: 1.3%) on the
      aged group. Therefore further improvement of the accuracy of the gastric mass
      survey in the aged group can be achieved by the gastro-endoscopy as the close
      examination. As the accuracy of the gastric mass survey was different from the
      institution to the institution and from the area to the area, particularly in the
      direct fluoro-radiography, but not in the gastro-endoscopy, depending on the
      training group of area, the later should be performed for the subjects for whom
      the former had been done at first. In addition to lectures, demonstration of
      practical techniques of the examinations should be displayed for the improvement
      of the gastric mass survey. The necessity of the gastro-endoscopy for the final
      diagnosis of gastric cancer should be understood by the subjects who was examined
      and person engaged in the gastric mass survey by the enlightment movement.

PMID- 8279243
TI  - [Cotard's syndrome in chronic schizophrenia].
AB  - A middle-aged woman who developed Cotard's syndrome after suffering from chronic
      schizophrenia is described. She had the delusion of negation believing that she
      had no possessions, but also her lung, heart, and intestines were gone. She also
      considered herself immortal. Medication was not useful in removing her delusions
      of negation and immortality.

PMID- 8279244
TI  - Tracheal intubation after induction of anaesthesia with propofol, alfentanil and
      lidocaine without neuromuscular blocking drugs in children.
AB  - In a double-blind study, intubating conditions and haemodynamic responses were
      assessed in two age-groups of 45 ASA I-II children, with mean ages of 2.4 and 6.3
      years, premedicated with oral midazolam and atropine. The children were randomly
      allocated to one of three groups: alfentanil 20 micrograms.kg-1 + lidocaine 1
      mg.kg-1 (Alf20 + Lign); alfentanil 20 micrograms.kg-1 (Alf20); or alfentanil 40
      micrograms.kg-1 (Alf40), followed by propofol 3.5 mg.kg-1 in the children aged 1
      3 years and 3.0 mg.kg-1 in the older children. Intubating conditions, 40 s after
      the administration of propofol, were assessed as good, moderate or impossible on
      the basis of jaw relaxation, ease of insertion of the endotracheal tube and
      coughing during intubation. In the younger age group the frequencies of good,
      moderate or impossible intubating conditions were 87, 13 and 0% in the Alf40, 40,
      60 and 0% in the Alf20 (P < 0.05 compared to the Alf40 group) and 53, 47 and 0%
      in the Alf20 + Lign group. In the older age group the corresponding frequencies
      were 60, 33 and 7% in the Alf20 + Lign, 47, 53 and 0% in the Alf20 and 47, 40 and
      13% in the Alf40 group. All the drugs prevented any increase in arterial pressure
      and heart rate after tracheal intubation. The QTc interval of the ECG was always
      in the normal range. Clinically important bradycardia did not occur. In
      conclusion, the best intubating conditions occurred after propofol 3.5 mg.kg-1
      and alfentanil 40 micrograms.kg-1 in the younger age group.(ABSTRACT TRUNCATED AT
      250 WORDS)

PMID- 8279245
TI  - Early and late recovery after major abdominal surgery. Comparison between
      propofol anaesthesia with and without nitrous oxide and isoflurane anaesthesia.
AB  - A comparison was made between early and late recovery after major abdominal
      surgery under intravenous anaesthesia with propofol (with and without nitrous
      oxide) or inhalational anaesthesia with isoflurane. Sixty patients were randomly
      allocated to one of three forms of anaesthesia: propofol, propofol/nitrous oxide,
      or isoflurane/nitrous oxide anaesthesia. All received fentanyl and vecuronium.
      Recovery was monitored during the first 2 h after extubation and on days 1, 2, 3,
      7 and 30 after surgery. Every 30 min during the first 2 postoperative hours, the
      Steward recovery scale, sedation, orientation, collaboration, and comprehension
      were assessed by a blinded observer. Psychomotor function was evaluated by
      computerised simple reaction time and finger tapping speed in 32 patients. A
      scale of symptoms and mood check list were filled in by 35 patients on days 1, 2,
      3, 7 and 30. The preoperative values for all tests were collected 1-4 days before
      surgery. The time between end of surgery and extubation was longer in the
      propofol group, but early and late recovery of psychomotor function were similar
      in the three groups. Patients anaesthetised with isoflurane reported more
      vegetative symptoms than those who received propofol (P < 0.03). The addition of
      nitrous oxide to propofol did not change the reported degree of symptoms. The
      difference in vegetative symptoms between groups was most obvious on day 7.
      Patients anaesthetised with propofol reported better subjective control (P <
      0.02) and were more socially oriented (P < 0.05) than patients anaesthetised with
      isoflurane. We conclude that early recovery was similar in the three
      groups.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279246
TI  - Comparison of cardiovascular changes during anaesthesia and recovery from
      propofol-alfentanil-nitrous oxide and thiopentone-halothane-nitrous oxide
      anaesthesia in children undergoing otolaryngological surgery.
AB  - Propofol/alfentanil anaesthesia was compared with thiopentone/halothane
      anaesthesia in 86 midazolam-atropine premedicated children undergoing minor
      otolaryngological surgery. The study was randomised, and evaluation of recovery
      from anaesthesia was double-blind. The children were divided into two age groups:
      1-3 years and 4 years and older. Particular attention was paid to ECG changes
      during anaesthesia and to the rapidity of recovery. One minute after alfentanil
      15 micrograms.kg-1, the children in the propofol group received propofol 2.0-3.0
      mg.kg-1 followed by propofol infusion 15 mg.kg-1.h-1. In addition, 0.1%
      suxamethonium 6 mg.kg-1.h-1 was infused during operation. The other children
      received thiopentone 5-7 mg.kg-1 followed by halothane (0.5-2%) immediately after
      endotracheal intubation. Junctional rhythm occurred in 5-35% of the children
      independent of anaesthesia method, and ventricular ectopic beats were seen in 20%
      of the older children during halothane anaesthesia. Recovery with respect to
      times to eye opening or response to verbal contact was significantly faster after
      propofol/alfentanil anaesthesia than after thiopentone/halothane anaesthesia in
      the older but not in the younger age group. Furthermore, in the younger age group
      significantly more crying occurred after propofol/alfentanil than after
      thiopentone/halothane anaesthesia. On the basis of this study,
      thiopentone/halothane anaesthesia is recommended for children aged 1-3 years and
      propofol/alfentanil anaesthesia for older children undergoing adenoidectomy
      and/or tonsillectomy.

PMID- 8279247
TI  - Nausea: the most important factor determining length of stay after ambulatory
      anaesthesia. A comparative study of isoflurane and/or propofol techniques.
AB  - Speed of recovery and length of stay in hospital were studied in 95 ambulatory
      patients undergoing laparoscopy or arthroscopy. The patients were divided into
      three groups regarding maintenance of anaesthesia. Group A (n = 32) received
      isoflurane 0.7% end-tidally, group B (n = 31) propofol infusion for 25 min and
      thereafter isoflurane, and group C (n = 32) received an infusion of propofol
      throughout the procedure. Recovery was assessed by a combination of the Maddox
      Wing, the Choice Reaction Time test and p-deletion. The awakening period was
      somewhat shorter in group A, but psychomotor recovery was somewhat slower
      compared to groups B and C. The length of stay in hospital depended on whether
      the patient was nauseated or not. In group A, 44% suffered from nausea requiring
      medical intervention compared to 13% and 19% in groups B and C, respectively. The
      stay in hospital was 235 +/- 90 min (mean +/- standard deviation) in group A
      compared to 184 +/- 56 min and 197 +/- 55 min in groups B and C, respectively.
      The non-nauseated patients in group A had a stay in hospital of 188 +/- 55 min
      compared to 184 +/- 52 and 184 +/- 37 in the non-nauseated patients in groups B
      and C, respectively. In total, the nauseated patients (n = 24) stayed 267 +/- 95
      min compared to 185 +/- 47 min for the non-nauseated patients (n = 71), P <
      0.001. We found nausea to be the most important factor determining length of stay
      after ambulatory anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279248
TI  - Diclofenac for pain relief after arthroscopy: a comparison of early and delayed
      treatment.
AB  - The effect of diclofenac on pain after arthroscopy of the knee joint was
      investigated in 64 patients. The aim of this double-blind, placebo-controlled,
      randomised study was to compare administration before surgery with delayed
      treatment. The effect on postoperative pain was evaluated by means of a Visual
      Analogue Scale and recording of the need for additional analgesics
      postoperatively. After surgery, hourly assessments were performed within 6 h
      after the anaesthetic block (approximately 5 h after start of surgery), and on
      the morning after surgery. Both treatment with diclofenac before surgery and
      delayed treatment were superior to placebo concerning pain scores within 6 h
      after onset of anaesthesia (P < 0.0065 and P < 0.0005, respectively). On the
      morning after surgery, only delayed treatment was superior to placebo (P < 0.02).
      No differences in pain scores were evident between the different groups treated
      with diclofenac. No differences in the need for additional analgesics were found.

PMID- 8279249
TI  - Comparison of acute central nervous system and cardiovascular toxicity of 2
      chloroprocaine and prilocaine in the rat.
AB  - In this study, we compared the central nervous system and cardiovascular system
      toxicity of i.v. administered 0.5% 2-chloroprocaine (N = 10) and 0.5% prilocaine
      (N = 10) in lightly anaesthetised rats. Arterial blood pressure, ECG and EEG were
      continuously recorded. Prilocaine produced the predetermined toxic end-points
      (i.e. seizure activity on EEG, isoelectric EEG, cardiac arrhythmia on ECG,
      asystole on ECG) at significantly lower doses than 2-chloroprocaine (P < 0.05).
      The mean dose of prilocaine producing asystole was 166 mg.kg-1 (+/- 45 mg.kg-1,
      s.d.) vs. 255 mg.kg-1 (+/- 42 mg.kg-1) for 2-chloroprocaine (P < 0.01). The rate
      of decrease of mean arterial blood pressure during the infusion was significantly
      faster with prilocaine (P < 0.01). Typically, arrhythmias did not appear until
      just before asystole, suggesting that neither of the local anaesthetics possessed
      marker arrhythmogenic properties. It is concluded that prilocaine is slightly
      more toxic than 2-chloroprocaine in the rat, but that both local anaesthetics
      have a wide margin of safety. Doses producing seizure activity on the EEG
      (prilocaine 53 mg.kg-1 and 2-chloroprocaine 70 mg.kg-1, on average) are much
      higher than those used in clinical practice (usually < 10 mg.kg-1).

PMID- 8279250
TI  - Management of a giant intracranial aneurysm using surface-heparinized
      extracorporeal circulation and controlled deep hypothermic low flow perfusion. A
      case report.
AB  - Extracorporeal circulation with controlled hypothermic low flow perfusion was
      introduced during the surgical treatment of a patient with a giant intracranial
      aneurysm of the anterior communicating artery. Heparin-coated equipment (Carmeda
      Bio-Active Surface; CBAS) was utilized, thus reducing the need for systemic
      heparinization. Direct cannulation of the right atrium and aorta was established
      through thoracotomy. Blood flow through the circuit was kept at 4.5 l/min during
      normothermia. Core cooling, in combination with external surface cooling, was
      performed for 30 min to a temperature of 18 degrees C (nasopharynx). During a
      period of 25 min, the time for surgical repair of the aneurysm, blood flow was
      minimized to 0.4 l.min-1, equilibrating central and peripheral blood pressures to
      approximately 5-10 mmHg (0.65-1.3 kPa). Reperfusion was started immediately after
      the low flow period concomitantly with rewarming, aiming at a temperature of 36
      degrees C following 150 min. The patient could be weaned off the extracorporeal
      circulation with minimal inotropic support. The postoperative course was
      uneventful apart from a left-sided hemiparesis, probably due to an infarction in
      the area of the right pericallosal artery (A2). The patient was weaned off the
      ventilator after 6 days. He recovered and the hemiparesis regressed slowly.

PMID- 8279251
TI  - Distribution of radioactive microspheres injected into the vertebral artery of
      the dog.
AB  - The aim of the present study was to evaluate the use of the vertebral artery for
      cerebral blood flow studies. In eight dogs a small catheter was introduced into
      an unligated a. vertebralis sin. Radioactive microspheres (141Cerium) were
      injected and detected with a gamma camera. The microspheres were distributed to
      all parts of the brain. The concentrations were highest in the cerebellum, pons
      and medulla oblongata, while the total activity was greatest in the cerebrum
      because of its higher weight. The activity in the extracerebral tissues in the
      head was found to be less than 5% of the brain activity.

PMID- 8279252
TI  - Epidural analgesia with 4 mg of morphine following caesarean section: effect of
      injected volume.
AB  - The efficacy and side effects of epidural bolus injection of 4 mg of morphine in
      a volume of 2 ml, 10 ml, or 20 ml (groups I, II and III) for postoperative
      analgesia after caesarean section (60 patients) were evaluated. All patients had
      epidural anaesthesia established up to T4 level with 0.5% bupivacaine 18-20 ml,
      supplemented with 2% lidocaine with adrenaline, when necessary. Morphine 4 mg in
      either of the three volumes was injected through the epidural catheter in random
      order after delivery of the baby. Six patients in each group reported no pain
      during the 24-h follow-up period. No additional pain medication during the 24 h
      after surgery was required in 11, 14 and 10 patients in groups I, II and III,
      respectively. Most of the others managed with the addition of a single dose of
      rectal ketoprofen. There were no differences in analgesic therapy between the
      groups. Pruritus was the most common adverse effect (18/20, 19/20 and 18/20 in
      groups I, II and III, respectively). 10/20, 12/20 and 14/20 (N.S.) patients had
      nausea and vomiting in groups I, II and III, respectively. Metoclopramide,
      prescribed for persistent nausea, was given to 4/20 patients in group I, 6/20
      patients in group II and 9/20 patients in group III (N.S.). After removal of the
      urinary catheter 7/20 patient in group III required carbachol for urinary
      retention compared to 3/20 and 4/20 patients in groups I and II (N.S.).(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279253
TI  - Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on
      haemodynamic parameters, transcapillary fluid balance, diuresis and atrial
      peptides.
AB  - The effects of Ringer's acetate (RAc) infusion with different temperatures, 18
      degrees C compared to 36 degrees C, were studied in 20 healthy volunteers. An
      infusion volume of 20% of the estimated extracellular volume was given over 45
      min. Before and after the RAc infusion, interstitial colloid osmotic pressure and
      interstitial fluid hydrostatic pressure were measured on the lateral part of the
      thorax and in the lower leg. Blood sampling and pressure measurements were
      performed through a cannula placed in the left radial artery, and arterial oxygen
      saturation was measured by pulse oximetry. Atrial peptides ANF (99-126) and ANF
      (1-98) in plasma were measured as indicators of volume loading. Cold RAc infusion
      increased mean arterial pressure from 82 (s.d. +/- 7) to 96 (s.d. +/- 9) mmHg
      (10.9-12.8 kPa) at the end of the infusion with a simultaneous fall in heart
      rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The
      arterial oxygen saturation during the infusion of cold RAc was higher than during
      warm RAc infusion. Cold infusion produced the expected haemodilution with a fall
      in erythrocyte volume fraction (EVF) from 0.39 (+/- 0.03) to 0.33 (+/- 0.03) and
      a fall in plasma colloid osmotic pressure (COPp) from 21.7 (+/- 1.1) mmHg to 15.0
      (+/- 1.3) mmHg (2.9-2.0 kPa). Warm infusion induced a nearly identical
      haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (+/- 2.3)
      mmHg to 8.9 (+/- 2.7) mmHg (1.5-1.2 kPa) after warm infusion while cold infusion
      gave no changes. The changes in interstitial fluid hydrostatic pressure were not
      significant.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279254
TI  - Myoclonic spasms during treatment with high doses of intravenous morphine in
      renal failure.
AB  - Myoclonic spasms occurred in a patient suffering from renal failure after high
      doses of continuous intravenous morphine (100 mg/h). The concentrations of
      morphine, morphine-6-glucuronide and morphine-3-glucuronide (mumol/l) in plasma
      were: 1.93, 52.06 and 381.8, and in cerebrospinal fluid were: 1.02, 5.86 and
      61.82, respectively. The role of morphine and morphine glucuronides in myoclonic
      spasms is discussed.

PMID- 8279255
TI  - Effects of 2-, 4- and 12-hour fasting intervals on preoperative gastric fluid pH
      and volume, and plasma glucose and lipid homeostasis in children.
AB  - We evaluated 105 randomly-selected unpremedicated children aged 1-14 years to
      determine the effects of a 2-, 4- and 12-h preoperative fasting interval on the
      preoperative gastric fluid pH and volume, and plasma glucose and lipid
      homeostasis. Each child undergoing elective surgery ingested a large volume
      (approximately 10 ml/kg b.w.) of apple juice and then fasted for 2, 4 or 12 h
      before the estimated induction of anaesthesia. After induction of anaesthesia,
      gastric fluid was aspirated through a large-bore, multiorifice orogastric tube.
      Plasma concentrations of glucose, total ketone bodies, non-esterified fatty acid
      (NEFA), triglycerides, and cortisol were measured at the time of induction to
      evaluate the fasting interval effects on preoperative plasma glucose and lipid
      homeostasis. There were no significant differences between the three groups in
      either gastric fluid volume or pH. In addition, there were no significant
      differences between the groups with respect to the proportion with a pH < 2.5 and
      volume > 0.4 ml/kg b.w. Neither plasma concentrations of glucose, triglycerides,
      nor cortisol at the time of anaesthetic induction differed between the three
      groups. Both 4 and 12 h nil per os (NPO) caused an increase in lipolysis, which
      was presumably a compensatory mechanism to maintain normoglycaemia. The plasma
      NEFA and total ketone bodies concentrations were therefore significantly higher
      in these two fasting intervals than in 2 h NPO. These data suggest that a 2-h
      NPO, after a large volume of ingested apple juice, may offer additional benefits
      by preventing an increase in lipolysis during the fasting interval without either
      increasing the volume of gastric fluid or decreasing the gastric pH.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279256
TI  - Monitoring of neuromuscular transmission by electromyography (II). Evoked
      compound EMG area, amplitude and duration compared to mechanical twitch recording
      during onset and recovery of pancuronium-induced blockade in the cat.
AB  - The feasibility of the compound electromyogram (EMG) was evaluated during onset
      and recovery from pancuronium block in the tibialis anterior muscle of ten cats.
      The evoked EMG area, amplitude and duration of the total response and of the
      major negative deflection were evaluated and compared to the mechanomyogram
      during 0.1 Hz and train-of-four (TOF) stimulation. EMG areas and amplitudes were
      found to be linearly and similarly related to the mechanomyogram during onset and
      recovery. Slopes of the regression lines ranged between 1.00-1.02 and between
      1.10-1.22 during onset and recovery, respectively, with high individual
      correlation coefficients (> 0.95). The TOF ratio of the mechanomyogram was
      linearly related to the EMG TOF ratio during onset and to the square root of the
      EMG TOF ratio during recovery, with no differences between EMG areas and
      amplitudes, suggesting a higher initial recovery of the TOF ratio of the
      mechanomyogram during recovery. EMG duration increased as the level of block
      increased but was unsuitable for neuromuscular monitoring. Evaluation of the
      agreement between the two methods showed that the EMG may be from 15% below to
      10% above the mechanomyogram during onset and from 40% below to 45% above the
      mechanomyogram during recovery, in spite of high correlation coefficients. In
      contrast, agreement between EMG parameters was found to be high. In conclusion,
      EMG is more reliable than the mechanomyogram for evaluation of neuromuscular
      transmission in the cat. EMG amplitudes and areas both reflect the degree of
      neuromuscular blockade equally well.

PMID- 8279257
TI  - Intrathecal injection of lysine acetylsalicylic acid in the rat: a
      neurotoxicological study.
AB  - Lysine acetylsalicylic acid has been reported to induce analgesic effects in
      humans after intrathecal (i.t.) injection. Before conducting further studies in
      humans with this drug, it is important to evaluate potential toxicological
      effects on the spinal cord in animals. In the present study the effects of
      chronic intrathecal administration of provocative doses of lysine acetylsalicylic
      acid (L-ASA) on the rat spinal cord were evaluated using light and electron
      microscopy and a quantitative morphometric method. We also investigated the
      effects of single doses of the drug on the spinal cord blood flow (SCBF) using
      the laser-Doppler flowmetry technique. No histopathological changes or
      differences in number or density of neuronal cells could be seen after chronic
      administration of L-ASA as compared to controls. The SCBF decreased immediately
      after i.t. injection of a large dose (4 mg) of L-ASA and returned to predrug
      levels within 10 min. At the end of the experiment metabolic acidosis was
      detected, indicating a systemic effect of acetylsalicylic acid. It is concluded
      that no neurotoxic effects on the spinal cord were seen after chronic i.t.
      injection of L-ASA. From a neurotoxicological point of view, our findings do not
      contraindicate the spinal use of L-ASA in humans.

PMID- 8279258
TI  - Brain energy metabolism and blood flow during sevoflurane and halothane
      anesthesia: effects of hypocapnia and blood pressure fluctuations.
AB  - The effects of halothane and sevoflurane on cat brain energy metabolism and
      regional cerebral blood flow (rCBF) were evaluated during normo- and hypocapnia.
      Brain energy status was evaluated with phosphorous nuclear magnetic resonance
      spectroscopy (31P-MRS) and rCBF was measured by the hydrogen clearance method. A
      high concentration of halothane (3 MAC) impaired brain energy metabolism, while
      even a higher concentration of sevoflurane (4 MAC) had no untoward effect on
      brain energy metabolism. At 3 MAC of halothane, there were measurable decreases
      in brain phosphocreatine (69% of the control) and increases in brain inorganic
      phosphate (about 250% of control Pi), even though CBF was about 70% of the
      control value. During hypocapnia, the phosphocreatine levels began to decrease at
      a PaCO2 of 2.7 kPa with 2 MAC of sevoflurane (90% of the control), and at a PaCO2
      of 4.0 kPa with 2 MAC of halothane (92% of the control). rCBF had decreased to
      less than 50% of the control value when PaCO2 was < or = 2.7 kPa with 2 MAC of
      sevoflurane and < or = 4.0 kPa with 2 MAC of halothane. Abnormal brain energy
      metabolism was only observed when rCBF was decreased to less than half of the
      control (non-anesthetized and normocapnic) value. Following administration of a
      vasopressor, metaraminol, the abnormal brain energy metabolism induced by 2 MAC
      of halothane at a PaCO2 of 1.33 kPa was normalized in parallel with the improved
      rCBF values. We conclude that hyperventilation and fluctuating blood pressure
      contribute to the occurrence of abnormal brain energy metabolism during halothane
      and sevoflurane anesthesia. This is more pronounced with halothane than with
      sevoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279259
TI  - Technical problems with 32-gauge microcatheters in continuous spinal anaesthesia.
AB  - Technical problems with microspinal catheters for continuous spinal anaesthesia
      (CSA) are not unknown. The present case report deals with two unusual technical
      complications in CSA with 32-gauge spinal catheters. The first case shows a
      catheter with extraordinary elongation due to breakage of the embedded stylet.
      The second case shows a tear in the extracorporeal part of the catheter with
      leakage of the local anaesthetic and consequently failed spinal anaesthesia.

PMID- 8279260
TI  - The bronchial tree, lobular division and blood vessels of the harbor seal (Phoca
      vitulina) lung.
AB  - The lung of the harbor seal (Phoca vitulina) consists of the bilateral upper,
      middle and lower lobes. The right lung has four bronchiole systems, i.e., the
      dorsal, ventral, medial and lateral, whereas the left lung has the dorsal,
      ventral and lateral, but not the medial bronchiole system. The upper lobe is
      formed by the first bronchiole of the dorsal bronchiole system, and the middle
      lobe by the first bronchiole of the lateral bronchiole system. The remaining
      bronchioles constitute the lower lobe. The right pulmonary artery runs along the
      ventrolateral side of the right bronchus, across the ventral side of the right
      upper lobe bronchiole, then across the dorsal side of the right middle lobe
      bronchiole, and thereafter runs along the dorsolateral side of the right
      bronchus. The left pulmonary artery runs a similar course to that of the right.
      The branches of the pulmonary arteries mostly run along the dorsal or lateral
      side of the bronchiole. The pulmonary veins run mostly along the medial or
      ventral side of the bronchiole, and finally enter the left atrium with five
      veins.

PMID- 8279261
TI  - [Morphometric studies on the cortex and medulla of frontally sectioned kidneys in
      the Japanese adult].
AB  - The cortex and medulla areas, sectioned frontally, of 50 kidneys from 25
      dissecting cadavers were measured to determine the correlation between
      differences in sex, laterality, and age. The average parenchyma (cortex +
      medulla) area was 33.45 +/- 9.16 cm2 and was larger in men than women; there was
      no significant laterality, but the parenchyma area was negatively correlated with
      age. The average cortex area was 20.39 +/- 5.80 cm2 and was also larger in men
      than women; laterality was not significant, and the cortex area was negatively
      correlated with age. The average medulla area was 13.05 +/- 4.40 cm2, and no
      significant difference in sex or laterality was found. The medulla area was
      negatively correlated with age. Additionally, the average number of renal
      pyramids (medulla) was 6.24 +/- 1.45 on these sections. Difference in the average
      areas of cortex and medulla was significant. The medulla was exceptionally larger
      in two cases (4%). The ratio between the average area of the cortex and medulla
      (C/M ratio) was 1.67 +/- 0.56. No sex difference or laterality was found, nor was
      there a correlation between the C/M ratio and age or kidney size. The sectioned
      area of cortex was approximately 1.5 to 2 times larger than medulla. These
      results suggest that senile atrophy may occur at the same rate in the renal
      cortex as in the medulla.

PMID- 8279262
TI  - [Distribution and three-dimensional reconstruction of lymphatic vessels of the
      elbow joint capsule of rabbits].
AB  - Lymphatic vessels are believed to be distributed in the the depth of synovial
      membrane, but the details of this distribution remain to be fully elucidated. The
      synovial membrane is classified in part on the basis of histological
      characteristics, even in the same joint capsule, into three fundamental types:
      adipose type, areolar type, and fibrous type. In addition, the adipose and
      areolar types are involved in the absorption of synovial fluid. In this study,
      the distribution of lymphatic vessels was investigated with special reference to
      histological structure of the synovial membrane. The materials were prepared from
      11 elbow joint capsules of male 8 rabbits weighting 2-3 kg. Five specimens were
      stained with silver nitrate, and the remainder were stained with trichrome. All
      of the materials were serially sectioned and observed by light microscopy. Three
      dimensional reconstructions of lymphatic vessels were performed using Cosmozone
      2SA software (Nikon Co.) with a PC-9800 series microcomputer (NEC Co.) When the
      joint capsule is divided into synovial and fibrous layers in accordance with the
      Nomina Histologica Japonica, the fibrous layer is frequently connected with the
      epimysium of neighboring muscles. The synovial and fibrous layers are
      occasionally continuous with each other, without a distinct boundary. The number
      of lymphatic vessels in the synovial layer is small, and they originate in the
      vicinity of the border of the fibrous layer and pass over into the lymphatic
      vessels of the fibrous layer. Many lymphatic vessels were found in the fibrous
      layer, the majority of which come from the epimysium or perimysium close to the
      outer surface of the fibrous layer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279263
TI  - [Hard palate shape in the Japanese and Indian children on moire topography with
      lateral movement of a grating].
AB  - In the present study, the hard palate of Japanese and Indian children was
      investigated. These children lived in different geographical areas and have
      different cranial characteristics, pronunciation and eating habits. Fifty-one
      Japanese children (26 boys and 25 girls, 3 years of age) and 66 Indian school
      children (31 boys and 35 girls, 5-7 years of age). The maxillary negative cast
      models were observed and three-dimensional measurements were taken of the hard
      palate with moire Topography. The following results were obtained. 1. The palatal
      width and length in Japanese children was larger than the Indian children, but
      not in palatal height. The palatal height was significantly larger in the Indian
      children than in the Japanese children. 2. Observation of the moire fringes on
      the deepest palate by moire Topography shows that the Japanese children and
      Indian girls have a higher incidence of Crosswise type than Lengthwise type. The
      Indian boys have a slightly higher incidence of Lengthwise type than Crosswise
      type. The girls have a higher incidence of the Butterfly and Separate types than
      the boys. 3. The anteroposterior location on the deepest palate by moire
      Topography: the Japanese children have significantly higher incidences of
      anterior location than the Indian children. Changes of anteroposterior location
      between the ages of 5 and 7 in the Indian children: the prevalence of posterior
      location appears to increase with age. 4. The hard palate shapes of the Japanese
      children appear to be broad and shallow, but those of the Indian children appear
      to be narrow and deep. This difference appears to be more remarkable in the boys.
      The shape and size of the hard palate appears to be due to genetic differences,
      in addition to the weather conditions, pronunciation and eating habits.

PMID- 8279264
TI  - Right-left differences in the lengths of human arm and leg bones.
AB  - Right-left differences in the maximum length of the humerus and radius, and the
      femur and tibia of the leg in an archaic population were investigated. The
      materials consisted of skeletons dated to the Neolithic Jomon period excavated in
      eastern Japan. The results obtained in this study were compared with those of
      four other populations. Dominant side in the arm and leg bones were found to be
      dissimilar based on the mean right-left differences. The arm bones of right side
      were significantly longer than those of left. The leg bones of the left side were
      longer than those of the right. Mean right-left differences of female arm bones
      were usually greater than those of males. Obvious sex-differences could not be
      seen for leg bones. The mean right-left differences of the humerus seemed to be
      more variable than those of the other three bones.

PMID- 8279265
TI  - [Morphology of the ganglion cervicale superius in human fetuses and an adult].
AB  - Morphology of the ganglion cervicale superius (GCS) was studied on 16 sides of 10
      human fetuses and the 2 sides of an adult cadaver with a binocular
      stereomicroscope. The obtained results were as follows. GCS is fusiform on 8
      sides, takes the form of an eggplant on 3 sides, and is weakly constricted on 7
      sides. The GCS was symmetrical in 2 cases. The GCS lay slightly above the first
      cervical vertebra and extended downward to the superior half of the second
      cervical vertebra on 11 sides of fetuses. The level in the adult is lower than in
      the fetuses by one vertebra. The nervus caroticus internus (CI), originating from
      the superior pole of the GCS as a cephalic prolongation, comprises one bundle on
      14 sides, and splits into 2 bundles in the original position on 4 sides. The Nn.
      carotici externi (CE) arise from the medial part of the superior half of the GCS
      with several roots (the average number of roots: 3.4) on 17 sides. The CE
      communicates with the Rami pharyngei of the N. vagus and the N. laryngeus
      superior. The Rr. laryngopharyngei arise from CE on many sides. The N. jugularis
      originates from the laterosuperior side of GCS with one to three branches. On a
      few sides, the N. jugularis communicates with the N. vagus and the N.
      hypoglossus. The communicating branch between the Ggl. inferius of the N. vagus
      and the GCS was observed in all cases. The communicating branch between the R.
      ventralis of the Nn. cervicales and GCS is found in all sides, and the lower
      limit of the branch is at the ansa from C3 to C4. The Rr. laryngopharyngei (RL)
      arise from the medial part of the GCS with several branches near the CE, or it
      may arise from the CE or from both the GCS and the CE, and join with the N.
      laryngeus superior (laryngeal branch of RL:RL1), the Plexus pharyngeus
      (pharyngeal branch of RL:RL2) and CE (RL1 and RL2). It is found in a few sides
      that RL directly extends to the pharyngeal and laryngeal portions. The N.
      cardiacus cervicalis superior (CS), which originates from the anteroinferior
      portion or the inferior pole of the GCS, was found on all fetal sides. The
      average number of CS is 2.9. Some nerves, crossing from the CI to the root of CE
      over the A. carotis interna, were recognized on 15 sides of the fetuses and on
      both sides of the adult.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279266
TI  - [System development for data deposit and retrieval of the JAA using the
      Internet].

PMID- 8279267
TI  - Intubation and mineralization disturbances in the enamel of primary teeth.
AB  - This study was undertaken to examine the effects of intubation on the enamel
      development of primary teeth in children intubated during the first 3 months of
      life. The teeth of 35 children were examined clinically for signs of defects.
      Dental enamel defects were seen in 26 (74%) patients; enamel hypoplasia was seen
      in 15 and enamel hypomineralization in 19 cases. In eight patients both enamel
      hypoplasia and hypomineralization were found. There was a preponderance of enamel
      defects in the right maxilla, which supports the hypothesis that an early trauma
      to mineralizing primary teeth caused by laryngoscope may lead to dental enamel
      hypoplasia.

PMID- 8279268
TI  - On the relations between dietary habits, nutrients, and oral health in women at
      the age of retirement.
AB  - Intake of energy, nutrients, food items, and various oral health-related factors
      were studied in 116 women about 5 months before the age of their occupational
      retirement. The results were analyzed with oral health aspects as both
      independent and dependent variables. Edentulous women had higher intake of fat
      and higher coffee consumption than dentate ones, and dentate subjects with 1-20
      teeth had higher body mass index than those with > or = 21 remaining teeth.
      Individuals with high intake of energy and carbohydrates had more decayed tooth
      surfaces than those with low, but different intakes of other nutrients were not
      reflected in the studied tooth variables. Daily consumers of sweet beverages and
      sugar in coffee/tea had more decayed tooth surfaces than non-consumers. Nineteen
      of the 116 women with 'inadequate' diet did not differ from the others with
      regard to any of the studied tooth variables. Women with self-assessed chronic
      oral dryness had higher intake of energy, protein, iron, thiamine, and vitamin D
      than those without this problem. Smoking habits were reflected in the DMFS index
      but not in any of the other studied oral health-related variables. It was
      concluded that intake of energy- and sugar-rich products, frequencies of intakes,
      and oral dryness seem to be of greater importance for oral health than intake of
      specific nutrients, at least in this specific cohort.

PMID- 8279269
TI  - Relation between intra-articular temperature of the arthritic temporomandibular
      joint and presence of calcitonin gene-related peptide in the joint fluid. A
      clinical study.
AB  - Arthritic temporomandibular joints were investigated for intra-articular
      temperature and joint fluid content of calcitonin gene-related peptide. Eleven
      patients (16 joints) with rheumatoid arthritis, ankylosing spondylitis, psoriatic
      arthritis, or chronic unspecific polyarthritis or monarthritis participated in
      the study. The intra-articular temperature varied between 35.5 and 37.5 degrees
      C, with a mean of 36.5 degrees C. The concentration of calcitonin gene-related
      peptide varied between 7.5 and 749.0 pmol/l, with a mean of 108.6 pmol/l. There
      was a positive correlation between the intra-articular temperature and the joint
      fluid concentration of calcitonin gene-related peptide. The plasma level of the
      peptide was on an average 5% of the joint fluid level.

PMID- 8279270
TI  - Effect of experimental traumatic occlusion on blood flow in the temporomandibular
      joint of the rat.
AB  - Fluorescent microspheres (FM) were used to visualize and semi-quantify blood flow
      in the temporomandibular joint (TMJ) during experimental unilateral traumatic
      occlusion of the maxillary and mandibular molar teeth in 30 young rats. At
      different postoperative observation periods varying from 1 to 30 days FM were
      injected systemically, and the number of FM were counted in serial sections from
      the TMJ in a fluorescent microscope. Blood flow was related to the number of FM
      found in the fibrous connective tissue and bony condyle of the TMJ. A percentage
      increase in blood flow was found at 15 to 20 days on the experimental side,
      compared with the contralateral side. Furthermore, there was an increase in blood
      flow in both TMJs in the experimental animals compared with an unoperated control
      material of 10 animals. The study thus indicates that a local unilateral occlusal
      trauma initiates blood flow responses not only unilaterally but also in the TMJ
      on both sides in rats.

PMID- 8279271
TI  - Occlusal wear of teeth and restorative materials. A review of classification,
      etiology, mechanisms of wear, and some aspects of restorative procedures.
AB  - This paper is a literature review of various aspects of the wear of occluding
      tooth surfaces. It presents classification and terminology of occlusal tooth
      wear, and discusses etiology and differential diagnosis. It may be difficult to
      differentiate among abrasion, attrition, and erosion because there is nearly
      always a combination of the various processes. These processes of wear are
      described, and the in vitro and in vivo wear of some restorative materials is
      discussed. Treatment of severe tooth wear is considered difficult; prophylactic
      measures are therefore important. Some guidelines for restorative treatment of
      patients with extensive occlusal tooth wear are given, with special emphasis on
      the type of treatment, the vertical dimension of occlusion, the space available,
      and choice of material for the restorations.

PMID- 8279272
TI  - One-stage closure of isolated cleft palate with the Veau-Wardill-Kilner V to Y
      pushback procedure or the Cronin modification. III. Comparison of lateral
      craniofacial morphology.
AB  - The craniofacial morphology of 116 consecutive patients with isolated cleft
      palate was studied by means of lateral cephalograms at 17 to 20 years of age. One
      stage hard- and soft-palate closure had been carried out at the mean age of 1.8
      years by using the Veau-Wardill-Kilner or the Cronin mucoperiosteal palatal V-Y
      pushback technique. In the Veau-Wardill-Kilner group the cranial base was longer,
      the cranial base angle was larger, and the mandible longer and its ramus higher
      but less backward rotated. The patients with originally the most extensive clefts
      showed the most marked deviations in craniofacial morphology at adult age.

PMID- 8279274
TI  - [Arterial hypertension in the elderly. Experience at a hospital service].
AB  - High blood pressure in the elderly population is currently one of the most
      important public health problems. In recent years, a dramatic increase in life
      expectancy has occurred and cardiovascular diseases are now one of the major
      causes of morbidity and mortality in this age group. Therefore, high blood
      pressure in the elderly has been the aim of many trials throughout the world. In
      Medicine Department 1 of St. Maria Hospital, we designed and implemented a
      special outpatient follow-up for elderly people (> or = 65 years old) with
      hypertensive disease. At the end of the first year, 61 patients (22 men and 39
      women) with an average age of 71 years (SD +/- 5.3), with known of high blood
      pressure for an average of 10 years were treated with angiotensin converting
      enzyme inhibitor (11 patients), calcium channel blockers (6 patients), or a
      combination of both drugs. The mean blood pressure fell 15 mm Hg (SD +/- 19.6)
      without deterioration of the renal function. The echocardiographic evaluation
      showed reduction in the left ventricular dimensions without significant
      modifications of diastolic, systolic and cardiac output. In addition, there was a
      significant increase in attention/concentration and memory abilities, however the
      percentage of depressed patients was the same at the end of the first year of
      treatment for high blood pressure.

PMID- 8279273
TI  - The relationship between maximal bite force, bite force endurance, and facial
      morphology during growth. A cross-sectional study.
AB  - The aims of this investigation were to study the relation between facial
      morphology and bite force at different ages during growth and to investigate
      possible relations between bite force and the variables age, finger force,
      stature, and sex in growing healthy individuals. One hundred and thirty-six
      individuals were included, consisting of six groups of males and females, 7-9, 10
      12, and 20-24 years old. Standardized photographs were taken to determine the
      facial type. The occlusal relationship, body height, finger force, maximal bite
      force, and bite force endurance amplitude were recorded. All bite force variables
      and finger force increased with age in both sexes. A positive correlation was
      found between the maximal bite force in the incisor region and the ratio of upper
      to lower facial height; this is, subjects with a high bite force had a relatively
      short lower anterior height. The maximal bite force for molars and endurance
      amplitude were positively correlated to stature and finger force but not to
      facial characteristics. A longitudinal study to follow each individual child
      during growth would be of interest to evaluate the importance of muscular
      influence on facial growth.

PMID- 8279275
TI  - [CT study of 17 cases of congenital cochlear abnormality. Embryologic and anatomo
      functional relationship].
AB  - In this review of cochlear malformations, 17 cases were studied by CT scan (high
      resolution-target program) including 10 males and 7 females. The anomaly was
      bilateral in 12 cases and unilateral in 7 (the latter included 2 Mondini type
      aplasias and one Michel). The cochlear malformation (whose most frequent
      expression was the cochlear hypoplasia with 1 or 1 1/2 spires-65% of the cases)
      was associated to semicircular canals and/or vestibular aqueduct anomaly in 82%
      of the patients; it was exclusively of the anterior labyrinth in 18% of the
      cases. A middle ear malformation coexisted in 29%: in 3 cases with malleoincudal
      dysmorphy only and with tympanic aplasia in 2 others. These cochlear anomalies
      with CT expression were discussed considering the embryology, in view of a
      possible gestational dating, moreover relating to the hipocusia type: perceptive
      or combined.

PMID- 8279276
TI  - [Imaging of aortic aneurysms and dissections. Part 2. Aortic dissections].
AB  - The authors review the main imaging findings of aneurysms and dissections of the
      aorta. Based on the experience and imaging techniques available in their
      institution (Conventional Radiology, Sonography and Computed Tomography), they
      try to make a decision tree of radiologic procedures in ambulatory and emergency
      patients. Nowadays, in the majority of situations, these techniques allow the
      Radiologist to make the correct diagnosis, detect the complications and evaluate
      the patients in the pre and post-surgical phases. Other imaging techniques not
      available in their institution, such as Magnetic Resonance Imaging and
      Aortography, will be mentioned in view of their usefulness in some specific
      situations.

PMID- 8279277
TI  - [Primary lymphoma of the central nervous system in a patient with AIDS].
AB  - The increasing incidence of primary brain lymphoma appears to be real in
      immunologically normal people. However, lymphoma of the central nervous system
      has a much higher incidence in patients with immune deficient status as in renal
      and cardiac transplants, patients with IgA deficiency, or Wiskott-Aldrich
      syndrome. Thus, the increased predisposition of AIDS patients to brain lymphoma
      is not surprising, this being the second most frequent cause among cerebral mass
      lesions in the AIDS population. We report a case of a 36 year old white woman
      with AIDS and a cerebral mass lesion which we demonstrated to be a primary brain
      lymphoma.

PMID- 8279278
TI  - [Clear cell hepatocellular carcinoma].
AB  - A case of a 62 year old white patient with mild dyspeptic symptoms and nodular
      hepatomegaly is presented. The histologic examination of a liver biopsy revealed
      a hepatocellular carcinoma clear cell variant. There were no signs of chronic
      hepatic failure. The disease showed an indolent clinical behaviour, thus the
      beginning of chemotherapy was delayed until clinical deterioration was obvious.
      Clinical improvement was obtained with adriamycin. A review of the literature on
      this rare histologic variant of hepatocellular carcinoma is made.

PMID- 8279279
TI  - [Pedunculated polyp of the sigmoid. Initial detection by ultrasonography with
      compressive technique].
AB  - A man with a history of intermittent blood stained feces for 3 years was found
      with US to have a 3 cm polyp, presumably of the sigmoid colon. Double contrast
      barium enema and colonoscopy first missed the polyp, which was confirmed with
      surgery.

PMID- 8279280
TI  - [Complicated intestinal tuberculosis].
AB  - Differential diagnosis concerning Crohn's Disease and intestinal tuberculosis is
      often difficult. The authors present an illustrative case with ileal tuberculosis
      and secondary amyloidosis. Diagnostic tools and therapeutic measures are
      described. Literature review and theoretical discussion of both pathologies are
      included.

PMID- 8279281
TI  - [Angiography in the diagnosis of cerebrovascular pathology. Current indications
      and controversies].
AB  - The role of cerebral angiography in the diagnosis of cerebrovascular disease is
      currently being questioned due to both the increasing availability of carotid
      sonography and the recent introduction of Magnetic Resonance Angiography (MRA).
      After a technical foreword about the different modalities available today in
      Cerebral Angiography, we discuss its present indications (Conventional or Digital
      subtraction by intra-arterial route), in patients with extra and intra cranial
      atherosclerotic cerebro vascular disease, subarachnoid hemorrhage and arterial
      aneurysms, in vascular malformations, particularly arterio-venous malformations
      (AVM's), in occlusive non-atherosclerotic non hypertensive arteriopathies and in
      occlusive venous pathology. Although it is possible that the future will show us
      the progressive replacement of the invasive technologies by MRA, at the present
      stage of Magnetic Resonance development there is still an important role, if not
      crucial, for catheter angiography in the diagnosis of most of the diseases
      producing stroke syndromes.

PMID- 8279282
TI  - [Cancer and geriatrics].
AB  - Undoubtedly we are living in a world where life expectancy is growing larger and
      birth rates are decreasing; in the western world we are slowly progressing
      towards a world of elderly people. Such forecast rises a challenge with two
      multidisciplinary fronts: stabilizing or controlling the biological processes of
      aging. Since we cannot interfere with the genetic predetermination of life, the
      choice could be to block the events that might alter such genetic programme,
      preserving our genetic inheritance, as well as promoting a healthy life style and
      preventing diseases acquired through life. We must create social and economic
      conditions that permit more and more elderly people to be active members of the
      community, with preserved or restored mental and working capacities. There are
      several factors that can interfere with the life programme that is biochemically
      impressed in our genetic inheritance, by changing or disrupting homeostasis and
      thus provoking aggression or instability factors, within what I use to call the
      biological sociology of the human being. Among such factors, cancer prevails as a
      complex biological process that settles in the human body like a biological
      terrorist, and evolves to a nosologic process--cancer disease--that threatens
      life, first leading to disease and afterwards causing a genetically non expected
      death. Epidemiological studies show that age-related risk is a reality that
      neither individual involvement nor the New Biology resources can surpass.
      Therefore, I thought that Cancer and the Elderly would be an interesting subject,
      according to the following: 1. Topics on demography and geriatrics.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279283
TI  - Diagnostic and therapeutic stereotactic cerebral endoscopy.
AB  - Modern neuro-imaging caused a renewed interest in endoscopic techniques. Several
      indications for stereotactic endoscopy are illustrated. A prototype of a new four
      channel endoscope is used. Lesions in the posterior part of the third ventricle
      an even the fourth ventricle are reachable for biopsy. Cystic intra- or
      paraventricular lesions can be approached stereotactically and treated.
      Continuous rinsing is mandatory to preserve a clear vision.

PMID- 8279284
TI  - Therapeutic stereotactic procedures on the thalamus for motor movement disorders.
AB  - The value of functional neurosurgery in the treatment of motor movement disorders
      is emphasized. The two methods of stereotactic procedures, namely a destructive
      one with small lesions centered on specific targets, and a non-destructive one
      with chronically inserted electrodes connected with an also implanted
      programmable neuropacemaker are described in detail. The results in Parkinsonian
      tremor, essential tremor, tremor of multiple sclerosis, post-traumatic tremor and
      in other involuntary movement disorders are reported and demonstrate that
      stereotactic neurosurgical treatment of these conditions is a safe and
      efficacious method.

PMID- 8279285
TI  - Therapeutic stereotactic procedures on the thalamus for pain.
AB  - Thalamotomy and electrical stimulation of a thalamic target as treatment for
      persistent pain are discussed. Thalamotomy is only rarely performed these days
      according to a questionnaire, given to some colleagues, about the type and the
      number of operations they performed in the years 1984, 1985 and 1986. The need
      for stimulation in the periventricular or periaqueductal grey for nociceptive
      pain is decreasing due to the advent of intraspinal and intraventricular
      administration of opioids. Nowadays medial and lateral ventro-posterior thalamic
      nuclei are frequently stimulated for treatment of deafferentation pain. Of 36
      patients with deafferentation pain, 22 initially had benefit from this
      stimulation, but long-term success was only achieved in 11 (30%) of them. It was
      a general trend that the patients with an initial high pain relief score obtained
      the best long-term results.

PMID- 8279286
TI  - Indications for stereotactically-aided differential diagnosis: the neurologist's
      view.
AB  - The contribution of stereotactic biopsy (SB) in three pathological conditions;
      neoplastic disease, immunodeficiency states and degenerative cerebral atrophy, is
      reviewed. When craniotomy is contraindicated, SB is the most reliable method for
      demonstrating the neoplastic nature and the degree of malignancy of an
      intracranial space occupying lesion and may help to delineate it limits. In
      immunodepressed patients, SB is frequently used to differentiate tumours from
      opportunistic infections. In degenerative dementia, SB is susceptible of
      differentiating Alzheimer's disease from other degenerative conditions.

PMID- 8279287
TI  - Stereotaxy and behavioural disorders.
AB  - A series of 35 selected non senile patients was investigated with stereotactic
      brain biopsies in frontal and temporal lobes including the rhinencephalon.
      Results of neuropathological studies are confronted with clinical proposals.
      Alzheimer's disease is diagnosed in about 10% of the cases under 50 years of age,
      but more than 50% after 50. In the whole series only 10 clinical diagnoses (29%)
      were confirmed by neuropathological findings, 14 cases (40%) were fully
      corrected, 5 out of 7 undefined demented patients were specified but 6 cases
      (17%) remained unspecified because only nonspecific gliosis was found. Thus
      stereotactic biopsies were without real interest in 10 confirmed diagnosis (29%),
      of relatively poor interest in 6 nonspecific gliosis (17%), but of great interest
      in 19 cases (40% corrected + 14% specified = 54%). It can be considered from a
      general point of view that in our series more than 50% of diagnoses benefit
      definitively by stereotactic brain biopsies bearing in mind that the clinical
      diagnosis fails in one case out of two. It is clearly demonstrated that this
      stereotactic methodology has a significantly higher score than conventional
      biopsies.

PMID- 8279288
TI  - Technical possibilities and limitations of stereotaxy.
AB  - The availability of CT-Scanners and MRI coupled to stereotactic systems has made
      a stereotactic neurosurgical intervention an everyday tool. The indications,
      contra-indications and complications concerning intracranial tumours, the
      hypophysis, combined open stereotactic procedures, third ventriculostomy,
      diseases of the extrapyramidal motor system, pain, epilepsy, psychosurgery and
      the transplantation of embryonal cells are discussed.

PMID- 8279289
TI  - Stereotactic indications for neuroradiological differential diagnosis.
AB  - The modern neurodiagnostic techniques of MR imaging, CT scanning and angiography
      provide valuable morphological information that, although highly sensitive to
      tumour localisation, still lacks comparable specificity as to the exact
      histological nature of those lesions demonstrated. Biopsy remains necessary. To
      patients with potentially inoperable lesions or lesions best treated by
      chemotherapy or irradiation, modern techniques of neurosurgery now offer the
      option of precise stereotactic biopsy through small twist-drill burr holes as
      opposed to open biopsy. The interrelationships between MR, CT, angiography and
      stereotactic biopsy and their respective roles in the establishment of a
      definitive diagnosis are discussed.

PMID- 8279290
TI  - Stereotaxic target calculation. Theory and practice.
AB  - Modern neuro-imaging techniques have significantly increased the accuracy of
      stereotactic procedures and have thereby generated a renewed interest in guided
      brain surgery. This paper describes the neuroradiological aspects of stereotaxic
      target calculation (x-, y-, z- coordinates) using the Riechert-Mundinger (Fisher)
      frame for computed tomography (CT). Selected cases are shown, illustrating
      patient positioning, CT technique, target identification and calculation. The
      importance of obtaining pre- and post-stereotaxic CT examinations is emphasized.
      Finally, future developments such as magnetic resonance (MR) guided stereotaxis
      and integrated functional-anatomical computer generated 3-dimensional maps, are
      briefly discussed.

PMID- 8279291
TI  - Neuropathological diagnosis with stereotactic biopsies. Possibilities,
      difficulties and requirements.
AB  - The present paper is based on stereotactic biopsies (SB) of 870 patients during
      the last 20 years. Approximately 700 patients suffered with brain tumour.
      Dementias and various diseases such as vasculopathies, leucoencephalopathies and
      inflammatory lesions were diagnosed in the other cases. Three groups of problems
      can be diagnosed with SB: 1) deeply located brain lesions; 2) early stages of
      lesions and diffuse or multiple lesions detected with imaging techniques; 3) some
      progressive dementing or degenerative diseases. Multiple (generally 4 to 6) SB
      should be taken in the vicinity and various parts of the lesion; they should be
      numbered, described separately and located exactly on an image of the brain.
      Handling the SB with care and the quality of the processing are important.
      Previous contact between neurosurgeon and neuropathologist can improve the
      accuracy of the diagnosis, which is reliable in the majority of cases, without
      producing undesirable brain damage.

PMID- 8279292
TI  - Stereotactically guided radiosurgery using the linear accelerator.
AB  - Leksell initiated the concept of stereotactic radiosurgery in 1951. This last
      decade has seen a rapid proliferation in the development of the methodology which
      is certainly related in part to the simultaneous growth of high-resolution neuro
      imaging techniques. By focusing the beams of 201 hemispherically arrayed cobalt
      60 sources, the gamma-knife delivers a high dose of radiation to a small target.
      Another possibility proposed by several authors is the bragg peak cyclotron
      generated irradiation with accelerated protons or helium ions. In Lille, since
      1988, we have chosen to develop stereotactic radiosurgery, according to the
      system of Betti, by the association of Talairach's stereotactic methodology and
      external single-dose encephalic irradiation with high energy X-rays, delivered by
      means of a linear accelerator. The major indication for the use of this method is
      an arteriovenous malformation. Stereotactic radiosurgery may be proposed alone or
      in combination with surgery and embolisation. It has been shown to be a
      potentially effective treatment and an attractive alternative in carefully
      selected patients with intracranial tumours: slow-growing, well limited, deep
      seated tumours, such as some gliomas, acoustic neurinomas, skull base
      meningiomas, pituitary adenomas. This treatment is also used to deliver a focal
      boost of radiation to previously administered fractionated radiotherapy in
      patients with small gliomas and solitary brain metastases.

PMID- 8279293
TI  - Functional neurosurgery in the treatment of epilepsy in The Netherlands. Aspects
      of presurgical evaluation and the contribution of subdural and stereotactically
      implanted depth electrodes in the Dutch Workgroup for Functional Surgery.
AB  - In the Netherlands all patients who are considered candidates for surgical
      treatment of their epilepsy are referred to the Dutch Workgroup for Functional
      Neurosurgery. Resective neurosurgery in partial epilepsy is a focus of special
      interest of national health authorities. Annually 15-20 patients can now be
      operated upon. Presurgical evaluation includes a.o. 18/FDG PET. For depth-EEG
      recording a specially designed method of "Combined Subdural and Depth-EEG
      Recording" is used which has been described previously. 70 patients underwent
      depth-EEG recording with the combined method. In 4.2% of the patients there were
      transient complications, in 1.4% there was a possibly permanent slight
      neurological deficit caused by the method. Fifty-six patients were evaluated at
      least one year after their surgical treatment (median follow-up 3 years). In the
      frontal lobe group comprising 9 patients 56% were seizure-free, 76% benefited
      from the treatment. In the temporal lobe group with 47 patients 68% were seizure
      free and 92% benefited. No patient deteriorated from the resection. Permanent
      morbidity was nil.

PMID- 8279294
TI  - Electrical and magnetic stimulation of the central nervous system. Historical
      overview.

PMID- 8279295
TI  - Electrical stimulation of the human epileptic limbic cortex.

PMID- 8279296
TI  - Electrical stimulation with intracerebral electrodes to evoke seizures.

PMID- 8279297
TI  - Experimental phenomena evoked by human brain electrical stimulation.

PMID- 8279298
TI  - Sensorimotor cortical mapping and physiological response localization.

PMID- 8279299
TI  - Functional cortical mapping in children.

PMID- 8279300
TI  - Functional mapping of cortical language areas in adults. Intraoperative
      approaches.

PMID- 8279301
TI  - Functional mapping of memory and other nonlinguistic cognitive abilities in
      adults.
AB  - The review of previous research and the studies undertaken at our center suggest
      an important role for mapping of nonlinguistic cognitive functions with cortical
      stimulation. Such mapping is usually restricted to language functions, which is
      understandable given the importance of language to daily activities and the
      reports of postoperative declines in naming. However, memory functions are also
      critical to adaptive daily living, and these studies show that memory may be
      effectively addressed through mapping procedures. Both Ojemann's studies and
      those at our center suggest an important role for much of the temporal convexity
      in memory processing, and we believe that postoperative memory declines can be
      minimized with mapping of the temporal lobe prior to resection. Patients
      presenting with unique abilities that may be susceptible to postoperative
      declines can also be effectively mapped with stimulation studies tailored to
      their unique abilities. We encourage the expansion of mapping paradigms beyond
      just the language domain and believe that such studies will both improve the
      quality of our patients' functioning and further our knowledge of brain-behavior
      relationships.

PMID- 8279302
TI  - Physiological principles of electrical stimulation.

PMID- 8279303
TI  - Clinical applications of motor evoked potentials.

PMID- 8279304
TI  - Plasticity of cortical motor output organization following deafferentation,
      cerebral lesions, and skill acquisition.

PMID- 8279305
TI  - Intraoperative monitoring of the functional integrity of the motor pathways.

PMID- 8279306
TI  - Motor cortical stimulation for control of central deafferentation pain.

PMID- 8279307
TI  - Electrical stimulation-induced effects in the human thalamus.

PMID- 8279308
TI  - Cerebellar and thalamic stimulation for epilepsy.

PMID- 8279309
TI  - The treatment of prolonged coma with neurostimulation.

PMID- 8279310
TI  - Spinal root and proximal nerve stimulation.

PMID- 8279311
TI  - Electrical stimulation in selective dorsal rhizotomy.

PMID- 8279312
TI  - Intraoperative stimulation of the spinal cord for prevention of spinal cord
      injury.
AB  - There are several spinal cord stimulation methods available for eliciting an MEP.
      As with any procedure, there are strengths and weaknesses associated with each
      method that the examiner needs to become familiar with. Because each testing
      situation is different, a specific elicitation or recording technique may not be
      appropriate for all surgeries. For example, if tumor removal of the spinal cord
      is being performed, the examiner may wish to avoid using an EMG in order to
      eliminate the possibility of patient movement. Therefore, before initiating the
      use of any method for eliciting an MEP, it is the examiner's responsibility to
      become thoroughly familiar with the technique under consideration. Regarding the
      NMEP procedure, we feel very confident with this method for monitoring motor
      tract function. Although a "true" myogenic MEP is the preferred type of response
      to record, we believe that this response is too unreliable and insensitive for
      our use. We also believe that any weaknesses associated with the NMEP are more
      than offset by its strengths. In conclusion, the results from studies described
      in this chapter indicate that spinal cord stimulation does elicit an MEP. Based
      on the testing situation, either a myogenic or NMEP can be recorded and can
      provide the surgeon with information regarding motor tract function. However, it
      does not appear that information regarding total spinal cord function can be
      obtained by using only SEPs. In order to provide the surgeon with this
      information, an SEP and MEP method must be administered.

PMID- 8279313
TI  - Spinal cord stimulation for chronic, intractable pain.

PMID- 8279314
TI  - Transcranial electrical and magnetic stimulation.

PMID- 8279315
TI  - Electrical stimulation to modify detrusor function.
AB  - Electrical stimulation to modify detrusor function is now being used in humans.
      The sacral foramen electrode is currently the only implantable device used to
      inhibit bladder contractility. Stimulation of a bladder contraction requires
      electrode placement around the anterior sacral root. Dorsal rhizotomy, preferably
      performed intradurally, is necessary to abolish detrusor hyperreflexia, thus
      increasing functional bladder capacity. Stimulation of the anterior sacral root
      then results in detrusor contraction.

PMID- 8279316
TI  - Insights into cerebral function revealed by magnetic coil stimulation.

PMID- 8279317
TI  - Neural origins of the motor evoked potential. Experimental approach.

PMID- 8279318
TI  - Electrical stimulation of the human cerebral cortex. Theoretical approach.

PMID- 8279319
TI  - Electrocorticography during cortical stimulation.

PMID- 8279320
TI  - Clinical proton MR spectroscopy of neurodegenerative disease in childhood.
AB  - PURPOSE: To determine the contribution of MR spectroscopy in the assessment of
      childhood neurodegenerative disease. METHODS: Fifty-one subjects (7 weeks to 17
      years of age), 22 with either hereditary (n = 16) or acquired (n = 6)
      neurodegenerative disorders and 29 age-matched control subjects, were studied
      with combined proton MR spectroscopy and MR imaging. Single-voxel (2.0-8.0 cc) MR
      spectra were acquired at 1.5 T, with either short-echo-stimulated echoes and/or
      long-echo spin echoes. RESULTS: MR spectra exhibited signals from n-acetyl-,
      creatine-, and choline-containing compounds, neurotransmitters (glutamate),
      intracellular mediators (inositols), and glycolytic products (lactate). Abnormal
      MR spectra in neurodegenerative disorders reflected: demyelination, neuronal
      loss, and gliosis (increased mobile lipid presence and reduction of n
      acetylaspartate to choline); metabolic acidosis (lactate accumulation); and
      neurotransmitter neurotoxicity (increased glutamate, glutamine, and inositols).
      CONCLUSION: Proton MR spectroscopy may complement MR imaging in diagnostic
      assessment and therapeutic monitoring of neurodegenerative disorders.

PMID- 8279321
TI  - The mucopolysaccharidoses: characterization by cranial MR imaging.
AB  - PURPOSE: To characterize MR findings in mucopolysaccharidoses (MPS), to aid in
      diagnosis and categorization, and to define the role of MR in preoperative
      evaluation. MATERIALS AND METHODS: Six children with Hurler syndrome (MPS IH),
      five with Hunter syndrome (MPS II), and three with Sanfilippo A syndrome (MPS
      IIIA) were studied by routine T1-weighted and T2-weighted images at 1.5 T. MR
      findings were graded retrospectively. RESULTS: All had hallmark cribriform
      changes (sieve-like or multicystic) involving peri- and supraventricular,
      parietal, white matter (12), corpus callosum (8), and basal ganglia (4), which
      did not enhance. The cerebellum and brain stem were not involved with these
      cribriform changes. The most severe degree of cribriform changes occurred in
      children with Hunter and Hurler syndromes, correlating with non-central nervous
      system somatic involvement, but inversely related to degree of atrophy,
      ventricular enlargement, and white matter changes. Mental retardation was most
      severe in children with Hurler syndrome and correlated with chronicity of the
      disease. Severity of mental retardation did not correlate with severity of
      cribriform changes. CONCLUSIONS: Based on our observations, we postulate that in
      the natural course of MPS, cribriform changes occurred first, followed by white
      matter changes and, last, atrophy. More severe degrees of cribriform changes plus
      involvement of the corpus callosum may suggest a poorer prognosis. Optimal
      therapeutic intervention may be at the time of cribriform changes before atrophy
      has occurred. MR can define and grade these changes.

PMID- 8279322
TI  - Pediatric and adolescent oligodendrogliomas.
AB  - PURPOSE: To review the clinical and imaging findings in pediatric and adolescent
      intracranial pure oligodendrogliomas. METHODS: The clinical, CT, and MR data in
      39 surgically proved pure oligodendrogliomas were retrospectively reviewed.
      RESULTS: The frontal or temporal lobes were involved in 32 (82%) cases. Seventy
      percent of the tumors were hypodense on CT, three-fourths were hypointense on T1
      weighted images, and all were hyperintense on spin-density and T2-weighted
      images. Fewer than 40% of the lesions demonstrated calcification, and nearly 60%
      had well-defined margins. Mass effect was seen in fewer than half of the cases,
      and edema could be separately identified in only one case. Tumor enhancement was
      seen in fewer than 25%. In 39 cases after partial (3), subtotal (16), or total
      (20) resection, follow-up studies demonstrated stability over a mean period of 5
      years. CONCLUSION: The findings in this pediatric series of pure
      oligodendrogliomas (without mixed cell elements) differ from previous adult
      series in that calcification, contrast enhancement, and edema are seen less
      frequently. In addition, very slow or no growth is often characteristic, and
      these patients have an excellent prognosis with surgical resection.

PMID- 8279323
TI  - Cerebrospinal fluid flow measured by phase-contrast cine MR.
AB  - PURPOSE: This prospective study was designed to establish the temporal and
      quantitative relationship between blood flow and cerebrospinal fluid (CSF) flow
      using a phase-contrast cine MR pulse sequence. METHODS: A cine phase-contrast MR
      pulse sequence using peripheral gating was used to measure CSF flow direction and
      velocity. Data were acquired continuously and interpolated into 16 images
      throughout the cardiac cycle. RESULTS: The timing of systolic CSF flow in the
      cervical subarachnoid space (SAS) correlated very closely to the brain
      arteriovenous blood flow difference during the cardiac cycle. This arteriovenous
      difference was a measure of brain expansion. Aqueduct CSF flow during the cardiac
      cycle differed from SAS flow in that systolic flow was delayed in comparison with
      systolic cervical SAS flow. The normal aqueductal oscillatory flow volume was 1.7
      +/- .4 mL/min or 0.03 +/- 0.01 mL per cardiac cycle. This represented 14.5% +/-
      3.1% of the total CSF flow and tissue displacement through the incisura which was
      14.5 +/- 2.2 mL/min or 0.22 +/- 0.03 mL per cycle. CSF oscillatory flow volume in
      the cervical SAS was 39.0 +/- 4.0 mL/min or 0.65 +/- 0.08 mL per cycle.
      CONCLUSION: CSF flow can be measured. Results in healthy subjects show relatively
      low oscillatory flow through the aqueduct which is slightly out of phase
      (delayed) compared with SAS CSF flow.

PMID- 8279324
TI  - The cochlear nuclear complex: MR location and abnormalities.
AB  - PURPOSE: To determine the usefulness of MR imaging in locating known structural
      landmarks of the cochlear nuclear complex (CNC), and to determine the frequency
      of CNC abnormalities, based on these landmarks, in patients referred for MR
      evaluation of unilateral sensorineural hearing loss. SUBJECTS AND METHODS: We
      studied 12 consecutive months of temporal bone/posterior fossa MR images
      retrospectively to find four known structural landmarks of the CNC: the
      vestibulocochlear nerve root entry zone; the cerebellar flocculus; the
      curvilinear choroid plexus along and protruding from the foramen of Luschka; and
      the bulge of the CNC into the lateral recess of the fourth ventricle and the
      foramen of Luschka. We tabulated the number of landmarks located per CNC and the
      number and type of CNC MR abnormalities. Medical records were then reviewed to
      tabulate clinical indication for MR imaging, type of hearing deficit, and
      etiology of the hearing deficit and clinical-pathologic proof. RESULTS: 175
      patients (ages 15-75 years) provided 350 CNCs for study. All 350 CNCs showed at
      least three of the four landmarks. Thirteen of the 175 patients (7.4%) had focal
      CNC MR abnormalities; 136 of these 175 patients had been referred for MR
      evaluation of unilateral sensorineural hearing loss. In 10 of these 136 patients
      (7.4%), the CNC abnormalities shown on MR proved to be the cause of the
      sensorineural hearing loss. CONCLUSIONS: MR reliably delineates the CNC. Over 1
      year, approximately 7% of patients referred for MR evaluation of unilateral
      sensorineural hearing loss had MR-determined focal CNC abnormalities that caused
      the sensorineural hearing loss.

PMID- 8279325
TI  - Cerebellopontine angle invasive papillary cystadenoma of endolymphatic sac origin
      with temporal bone involvement.
AB  - The authors report the MR, CT, and pathologic findings in a case of invasive
      papillary cystadenoma originating in the endolymphatic sac and involving the
      temporal bone. This case illustrates characteristic imaging features of this
      lesion. The authors emphasize awareness of this entity with its aggressive
      temporal bone involvement as an aid to pathologic differential diagnosis.

PMID- 8279326
TI  - Routine use of contrast-enhanced MR scans in AIDS.

PMID- 8279327
TI  - Third cranial nerve palsy caused by gummatous neurosyphilis: MR findings.
AB  - The clinical and MR findings in an unusual case of gummatous neurosyphilis are
      reported. A 44-year-old woman suffering from diplopia and right-sided headaches
      was admitted. Physical examination and routine laboratory parameters were normal
      except for a third-nerve palsy. MR images revealed a contrast-enhancing lesion of
      the upper brain stem and third cranial nerve. Differential diagnosis included
      neuroma of the third cranial nerve, as well as neurosarcoidosis and other
      inflammatory processes. Serologic tests and lumbar puncture revealed the presence
      of active syphilis. After intravenous treatment with penicillin G, follow-up MR
      examinations showed diminishing size of the lesion with its complete resolution
      within 3 months.

PMID- 8279328
TI  - Asymmetric mamillary bodies: MR identification.
AB  - We report three cases in which there was marked asymmetry of the mamillary
      bodies, noted on MR in two and at autopsy in the third. Based on its proposed
      pathogenesis, we suggest that this finding could have value in locating temporal
      lobe disease in patients with intractable epilepsy.

PMID- 8279329
TI  - MR findings after depth electrode implantation for medically refractory epilepsy.
AB  - PURPOSE: To evaluate using MR imaging chronic changes in the brain parenchyma
      after electroencephalography depth electrode placement in patients with medically
      refractory epilepsy. METHODS: A retrospective review of MR scans in 57 patients
      who underwent stereotactic placement of 210 depth electrodes was performed. Scans
      were evaluated for evidence of gliosis, hemorrhage, or infection along the probe
      tracts. RESULTS: Signal abnormalities along the probe tracts were seen in 38
      patients (67%). Of the 210 probe tracts evaluated on long-repetition-time images,
      85 (41%) were associated with punctate hyperintensity and four (2%) with punctate
      hypointensity; 120 (57%) showed no MR changes to suggest prior electrode
      placement. One probe placement was complicated by a significant intraparenchymal
      hemorrhage. CONCLUSIONS: Depth electrode implantation for electroencephalography
      monitoring results in imperceptible or minimal chronic changes as detected by MR
      in almost all patients. The punctate hypersensitivity on long-repetition-time
      images is though to be caused by gliosis along the probe tracts. These signal
      changes should not be confused with the seizure focus. Significant hemorrhage or
      infection is a rare complication of probe placement. Incorporation of MR
      angiographic data with conventional spin-echo images at the time of stereotactic
      probe placement may further reduce the low incidence of probe-related hemorrhage.

PMID- 8279330
TI  - MR of diffusion slowing in global cerebral ischemia.
AB  - PURPOSE: To investigate the causal connections between ischemia and the
      hyperintensity in diffusion-weighted MR images that has been associated with it.
      METHODS: Diffusion-weighted and T2-weighted MR imaging were used in a feline
      global cerebral ischemia/reperfusion model. Single 30-minute vascular occlusions
      followed by reperfusion were studied. Global occlusions were used to avoid
      interpretive complications associated with the temporally unstable hemodynamics
      of the penumbral zones around focal occlusions and the possible growth of the
      ischemic and penumbral regions with time. RESULTS: Diffusion-weighted
      hyperintensity and the associated diffusional slowing were not attributable
      exclusively to the cessation of blood flow because: 1) it does not appear
      abruptly at the onset of ischemia; 2) it resolves slowly early in reperfusion;
      and 3) it reappears after prolonged reperfusion. CONCLUSION: The times during
      which diffusion-weighted hyperintensity is manifested during ischemia, and
      recovers with reperfusion, point to a role for energy metabolism failure.

PMID- 8279331
TI  - The fornix.

PMID- 8279332
TI  - Ocular melanoma.
AB  - Uveal melanoma is the second most frequent ocular malignancy after metastasis and
      the most common primary ocular malignant neoplasm in adults. The diagnosis is
      usually made from clinical examination and ocular ultrasound. CT and MR may be
      helpful for further evaluation.

PMID- 8279333
TI  - MR of head and neck adenopathy in asymptomatic HIV-seropositive men.
AB  - PURPOSE: Adenopathy is a well-known component of AIDS-related complex. Our goal
      was to determine whether asymptomatic HIV-infected persons have characteristic
      findings of head and neck adenopathy on MR imaging and whether there is an
      association between the MR findings and the CD4 lymphocyte counts. METHODS: We
      blindly and retrospectively evaluated the distribution and size of
      lymphadenopathy seen on screening MR examinations that were performed on 50
      asymptomatic HIV-positive male subjects and 50 age-matched HIV-negative control
      subjects. We also correlated the imaging findings in HIV-seropositive and 
      seronegative subjects with their CD4 counts. RESULTS: The HIV-positive subjects
      had a higher incidence of adenopathy compared with the controls. Statistically
      significant differences were found between the groups in size and number of neck
      lymph nodes, thickness of the adenoids, size of high, deep cervical
      retropharyngeal lymph nodes, and presence of parotid abnormalities. We found a
      correlation between increasing lymph node size and decreasing CD4 levels.
      CONCLUSION: We conclude that HIV-positive asymptomatic patients have a high
      incidence of head and neck abnormalities including lymphadenopathy, and
      alteration in their CD4 counts not commonly seen in seronegative control
      subjects.

PMID- 8279334
TI  - MR quantification of cerebral ventricular volume using a semiautomated algorithm.
AB  - PURPOSE: A semiautomated border identification algorithm, insensitive to user
      bias, is evaluated for accuracy and speed in the measurement of ventricular
      volumes from three-dimensional MR images. METHODS: A three-dimensional gradient
      echo technique was implemented on a Signa clinical imaging system. Data from
      phantoms and patients were analyzed for volume using a segmentation algorithm
      designed with: 1) correction for partial volume averaging; 2) insensitivity to
      user bias; and 3) speed. Accuracy, precision, and intra- and interobserver
      variability were determined. RESULTS: Average error for phantom studies was 4% to
      6%, or 1 to 2 cc across the volumes, which ranged from normal to mild
      hydrocephalus (< 60 cc). Patient studies showed intra- and interobserver error of
      2.3% and 7.8%, respectively. The correction for partial volume averaging resulted
      in a threefold decrease in error. Data were acquired and reconstructed within 7
      minutes. Experienced radiologists required less than 15 minutes to perform each
      analysis. CONCLUSIONS: This algorithm allows accurate measurement of ventricular
      volumes in an efficient, minimally supervised manner.

PMID- 8279335
TI  - Gadolinium-enhanced nerve roots in lumbar disk herniation.
AB  - PURPOSE: To analyze contrast-enhanced features of intrathecal nerve roots in
      lumbar disk herniation in patients who have not had surgery and to evaluate the
      possible correlation with herniated disk, peridiscal enhancement, and
      symptomatology. METHODS: Twenty patients with a syndrome of lumbar herniated disk
      without surgery were studied with pre- and postcontrast MR imaging. RESULTS: In
      six patients (30%), ipsilateral intradural roots affected with large disk
      herniations showed consistent enhancement along their whole length, from the site
      of compression to the root-medullary junction. This enhancement persisted on
      delayed scanning. "Selective" enhancement differed from the minimal enhancement
      seen in normal intrathecal roots in 11 (55%) patients. Enhancement around
      herniated disks was a common finding (92% of patients) and did not correlate with
      selective or normal root enhancement (P > .05). No symptom differences were found
      among patients with and without selective enhancement. CONCLUSION: Selective
      intrathecal root enhancement seems to be the direct visualization of the
      radiculopathy resulting from disk herniation. It is probably a transient event
      more likely to be noted in the acute phase. Although there is no evidence of
      immediate clinical utility of this finding, gadolinium-enhanced MR gives insights
      into the basic pathophysiologic alterations involved in degenerative disk
      disease.

PMID- 8279336
TI  - Intramedullary abscess, an unusual manifestation of a dermal sinus.

PMID- 8279337
TI  - Pleomorphic xanthoastrocytoma, a distinctive astroglial tumor: neuroradiologic
      and pathologic features.
AB  - PURPOSE: To analyze and discuss CT and MR features of pleomorphic
      xanthoastrocytoma (PXA) and present salient histopathologic features of this
      distinctive astroglial tumor. METHOD: CT, MR, and histopathologic studies on
      seven patients with the histologic diagnosis of PXA were reviewed
      retrospectively. RESULTS: All patients were in their first 3 decades of life when
      first diagnosed and demonstrated peripherally situated supratentorial tumors of
      varying size involving the superficial cortex and leptomeninges. Five of six
      cases examined with CT showed areas of mixed attenuation with four demonstrating
      well-demarcated enhancement. MR demonstrated low or mixed signal intensity on T1
      weighted and high or mixed signal intensity on T2-weighted sequences. All five
      who received gadopentetate dimeglumine showed well-defined enhancement. Three
      showed cyst formation. Typical histologic features included marked cellular
      pleomorphism with giant cells, bizarre nuclei, variable cytoplasmic lipidization
      and positive immunoreactivity for glial fibrillary acidic protein. Necrosis and
      endothelial-pericytic cell proliferation were absent. CONCLUSION: PXA has a
      highly suggestive neuroradiologic and distinctive histopathologic appearance.

PMID- 8279338
TI  - Recognition of the aberrant right subclavian artery on cervical spine MR.
AB  - Neuroradiologists performing cervical spine MR scans are reminded that an
      aberrant right subclavian artery is detectable on sagittal cervical spine views.
      This review of 335 consecutive patients revealed two such anomalies for a
      prevalence of 0.6%, which compares favorably with the published range of
      occurrences in the literature (0.5 to 2%).

PMID- 8279339
TI  - MR in idiopathic central diabetes insipidus of childhood.
AB  - We present the cases of two children with presumed idiopathic central diabetes
      insipidus whose follow-up MR studies eventually revealed hypothalamic tumors.
      Thin-section sagittal T1-weighted MR with gadolinium administration is important
      in the evaluation of these children, and serial examinations are probably
      necessary.

PMID- 8279340
TI  - Marc Jouandet: recipient of the Cornelius Dyke Award for 1993.

PMID- 8279341
TI  - Harold O. Peterson, MD: a life in neuroradiology.

PMID- 8279342
TI  - Role of MR imaging in the evaluation of the functional status of the posterior
      pituitary gland: the view of a pediatric endocrinologist.

PMID- 8279343
TI  - Tissue plasminogen activator in acute stroke.

PMID- 8279344
TI  - 1972 Einstein neuroradiology course.

PMID- 8279345
TI  - Primary angioplasty for acute myocardial infarction in 1,000 consecutive
      patients. Results in an unselected population and high-risk subgroups.
AB  - Primary angioplasty (direct angioplasty without antecedent thrombolytic therapy)
      has remained an exclusive and consistent method of infarct intervention at our
      institution over the past 13 years. A total of 1,000 consecutive patients were
      prospectively enrolled in our primary angioplasty database. Of patients
      presenting to our group with an acute myocardial infarction, 96% of those
      eligible received immediate angioplasty. Cardiogenic shock was noted in 79
      patients (7.9%). The mean time from pain onset to reperfusion was 5.4 +/- 4.0
      hours. Infarct-vessel recanalization was accomplished in 94% of patients.
      Recanalization rates were similar among the 3 native epicardial coronary systems
      but were lower in bypass grafts (86%; p < 0.0001). Overall in-hospital mortality
      was 7.8%; mortality with cardiogenic shock was 44%. Global ejection fraction
      increased from 49.7% preangioplasty to 57.4% at the time of dismissal. The amount
      of myocardial salvage was highly dependent on the size of the initial infarction
      (the largest infarctions benefiting the most). Patients reperfused in < 2 hours
      experienced a very low mortality (4%) and impressive myocardial salvage.
      Complications included stroke in 0.5%, significant bleeding in 2.8%, and early
      reocclusion of the infarct vessel in 13%. Primary angioplasty is broadly
      applicable to patients presenting with acute myocardial infarction and results in
      a very high rate of infarct vessel recanalization, with a mortality rate of 7.8%.
      This strategy may be uniquely effective in patients presenting with cardiogenic
      shock, large infarctions, contraindications to thrombolytic therapy, and prior
      bypass surgery.

PMID- 8279346
TI  - Mechanical manipulation of thrombus: coronary thrombectomy, intracoronary clot
      displacement, and transcatheter aspiration.
AB  - Recanalization of occluded arteries during acute myocardial infarction has been
      proven to prolong life and improve left ventricular function. Patients who could
      not receive thrombolytic therapy for failed thrombolysis and/or angioplasty were
      treated by mechanical manipulation of the thrombus. Three techniques were used:
      transcatheter aspiration, clot displacement, and thrombectomy. Five patients in
      shock had the thrombus aspirated from the left main and right coronary arteries.
      Eight patients had the clot pushed by the balloon from the mid-left anterior
      descending (LAD) to the apical LAD in order to reduce the area of ischemic
      myocardium, and 13 patients underwent a thrombectomy of the right coronary
      artery. These procedures enjoyed a high rate of success in reestablishing patency
      and a favorable long-term clinical and angiographic follow-up. Although the
      applicability and role of these interventions in acute myocardial infarction are
      not yet defined, we conclude that they are feasible and have an acceptable
      success and complication rate.

PMID- 8279347
TI  - Effects of coronary angioplasty on left ventricular function.
AB  - It is well known that myocardial revascularization after successful coronary
      bypass surgery results in improved left ventricular function. Coronary
      angioplasty also results in successful revascularization, favorably affecting
      both stunned and hibernating myocardium. We studied 22 patients with chronic
      stable angina who underwent successful angioplasty for an isolated narrowing of
      the proximal or midportion of the left anterior descending artery. These patients
      also performed isometric exercises before and after angioplasty, which can be
      used to characterize left ventricular function. Revascularization after
      angioplasty induced an immediate improvement in left ventricular function in
      those patients with dysfunction secondary to hibernating myocardium. Further
      studies are needed to assess the possibility of the myocardial stunning
      phenomenon occurring after angioplasty in those patients without left ventricular
      improvement.

PMID- 8279348
TI  - Dobutamine stress echocardiography for assessment of myocardial viability and
      ischemia in acute myocardial infarction treated with thrombolysis.
AB  - To evaluate the role of dobutamine echocardiography for early assessment of
      myocardial viability and ischemia in acute myocardial infarction (MI), 59
      patients with thrombolyzed acute MI underwent low- (5-10 micrograms/kg/min, 8
      patients) and high-dose (20-40 micrograms/kg/min, 51 patients) dobutamine
      echocardiography at a mean of 8 +/- 4 days after acute MI. Myocardial viability
      in the infarct zone was documented in 43 of 59 (73%) patients (group 1), in whom
      mean asynergy score index decreased from 1.6 +/- 0.3 at baseline to 1.3 +/- 0.2
      (p < 0.001), after low-dose dobutamine. No viability was present in 16 of 59
      (27%) patients (group 2). At follow-up, recovery of regional contractile function
      was observed in group 1 (asynergy score index decreased from 1.6 +/- 0.3 to 1.4
      +/- 0.3; p < 0.001), but not in group 2 patients. Sensitivity, specificity, and
      negative and positive predictive values of low-dose dobutamine echocardiography
      in predicting spontaneous recovery of function were 79%, 68%, 50%, and 89%,
      respectively. Of the 51 patients who underwent high-dose dobutamine, 26 of 36
      (72%) group 1 patients showed a deterioration of contractility in the infarct
      zone indicative of myocardial ischemia compared with only 1 of 15 (7%) group 2
      patients. At follow-up, recovery of regional function was greater in patients
      with no evidence of myocardial ischemia at high doses than in those with an
      ischemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279349
TI  - Reperfusion in acute myocardial infarction: effect of timing and modulating
      factors in experimental models.
AB  - Timely reperfusion of ischemic myocardium in experimental animals halts the
      advancing transmural "wavefront" of ischemic cell death and thereby limits
      myocardial infarct size by limiting its transmural extent. The time window of
      opportunity for such salvage in most experimental models of regional ischemia is
      the first 3 hours. The number of myocytes that can be salvaged by reperfusion
      decreases exponentially during this period, such that at 3 hours, reperfusion
      limits infarct size by only about 10%. The rate of lethal ischemic cell injury
      and therefore the amount of myocardium that can be salvaged by reperfusion after
      a particular duration of ischemia is dependent both on the degree of blood flow
      deficit and the rate of ischemic metabolism. In experimental animal models,
      several interventions, including hypothermia, calcium antagonists, and "ischemic
      preconditioning," have been shown to reduce the rate of ischemic metabolism and
      to limit myocardial infarct size when assessed after a defined period of ischemia
      and reperfusion. Hypothetically, interventions that could prevent additional
      myocyte necrosis caused by some deleterious aspects of reperfusion ("lethal
      reperfusion injury") also could serve as valuable adjunctive therapy. However,
      studies of therapies designed to prevent lethal reperfusion injury have produced
      conflicting results. Thus, the concept that lethal reperfusion injury occurs
      remains controversial. Experimental evidence indicates that reperfusion
      accelerates both the initial inflammatory response and later process of infarct
      repair. Late reperfusion of infarcts in dogs, which does not limit myocardial
      infarct size, appears to accelerate the replacement of necrotic myocardium by
      scar without altering the size of the final scar.

PMID- 8279350
TI  - Time dependence of residual tissue viability after myocardial infarction assessed
      by [18F]fluorodeoxyglucose and positron emission tomography.
AB  - Areas of myocardial infarction may retain glycolytic activity and this finding is
      indicative of tissue viability and predictive of functional recovery after
      revascularization. In order to assess the relation between the time elapsed from
      the occurrence of acute myocardial infarction and persistence of myocardial
      metabolic activity in the infarcted tissue, we prospectively studied 65 patients
      with previous myocardial infarction diagnosed clinically and by
      electrocardiographic (Q wave) and enzymatic criteria. All patients underwent
      coronary angiography and contrast left ventriculography, evaluation of regional
      myocardial glucose metabolism (in the fasting state) by positron emission
      tomography (PET) with 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), and assessment
      of myocardial perfusion by single photon emission computed tomography (SPECT)
      with technetium-99m methoxyisobutyl isonitrile (99mTc-MIBI). Based on the
      regional metabolic and perfusion findings, patients were divided into 2 groups,
      depending on the absence (group 1, 26 patients) or presence (group 2, 39
      patients) of [18F]FDG uptake in the underperfused regions. Areas of
      underperfusion at rest, consistent with the clinically identified myocardial
      infarction site, were observed in all patients. Severity of coronary artery
      disease, presence of collaterals, number of hypocontractile segments, and wall
      motion score did not differ significantly in the 2 groups. The time elapsed from
      the infarction was significantly greater (1,860 +/- 1,333 days) in group 1 than
      in group 2 (92 +/- 115 days; p < 0.0001). Exercise caused an increase in severity
      and/or extent of resting perfusion abnormalities in a greater proportion of
      patients of group 1 (53% vs 23%).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279351
TI  - Assessment of left ventricular function by isometric handgrip exercise after
      thrombolysis in patients with refractory unstable angina.
AB  - The handgrip test has been proposed for the evaluation of the hemodynamic reserve
      in patients with coronary artery disease and to quantitate the impairment of left
      ventricular (LV) function. The present study was designed to evaluate the effect
      of thrombolytic therapy in patients with refractory unstable angina in order to
      test the hypothesis that a reduction in intracoronary thrombosis could ameliorate
      their hemodynamic response to the handgrip test. During left heart
      catheterization, 20 patients with refractory unstable angina of recent onset
      performed a handgrip test before (HG1) and 24-72 hours after (HG2) being
      randomized to receive recombinant tissue-type plasminogen activator or placebo,
      according to a double-blind parallel group design. HG1 induced an increase in
      heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in
      ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during
      baseline handgrip were highly different in individual patients, resulting in a
      trend toward an increase. Similarly, a different individual response was observed
      in the behavior of the isovolumetric and relaxation indices. In comparison with
      HG1, no difference was detected during HG2 in the 2 treatment groups with respect
      to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures,
      +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable
      angina of recent onset, the handgrip test performed before and after thrombolysis
      did not prove to be useful in assessing directional changes of LV performance,
      mainly because of the different individual response to the baseline handgrip
      test.

PMID- 8279352
TI  - Maximizing benefits of therapies in acute myocardial infarction.
AB  - Major advances in the management of acute myocardial infarction have been
      achieved by a combination of careful experimental work and development of
      effective pharmacologic and interventional strategies in conjunction with the
      conduct of large, reliable randomized trials. Current trials indicate that a
      combination of thrombolytic therapy, aspirin, and intravenous followed by oral
      beta blockers reduces mortality. There are a number of additional promising
      interventions, such as intravenous magnesium, nitrates, and the newer
      antithrombin agents. However, before these agents are used widely in clinical
      practice, clear proof of benefit and adequate safety should be available from the
      ongoing randomized trials. Following discharge from the hospital, long-term
      therapy with aspirin and beta blockers should be considered in all patients. In
      patients with heart failure and low ejection fraction, angiotensin-converting
      enzyme (ACE) inhibitors have been shown to reduce mortality, reinfarction, and
      the need for further hospitalizations for heart failure. Therefore, these
      therapies, in conjunction with risk factor modification (cessation of cigarette
      smoking, treatment of hypercholesterolemia, treatment of hypertension), should be
      considered in all appropriate patients. A number of new strategies for the
      prevention of atherosclerosis and its complications are currently being evaluated
      in prospective randomized trials. These include the natural antioxidant vitamins,
      estrogen replacement therapy, tamoxifen therapy, and ACE inhibitors in patients
      without evidence of heart failure or left ventricular dysfunction.

PMID- 8279353
TI  - Effects of nitrate therapy on ventricular remodeling and function.
AB  - The hypothesis that nitrates might effectively limit left ventricular remodeling
      and improve function after acute myocardial infarction has been tested in
      experimental and clinical models, with special attention to the pathophysiologic
      evolution of remodeling. In 1 clinical study, before the thrombolytic era, the
      effects of low-dose intravenous nitroglycerin infusion for the first 48 hours
      during acute myocardial infarction was evaluated in a prospective, randomized,
      single-blinded, placebo-controlled study of 310 patients (154 nitroglycerin; 156
      placebo). Nitroglycerin proved to be safe and produced several benefits compared
      with placebo: (1) smaller infarct size; (2) less left ventricular dysfunction;
      (3) less infarct expansion and thinning; (4) better functional status; (5) fewer
      in-hospital complications such as left ventricular failure, left ventricular
      thrombus, cardiogenic shock, and infarct extension; and (6) fewer deaths up to 1
      year. Two subsequent clinical studies in the thrombolytic era, with low-dose
      intravenous nitroglycerin infusion during infarction over the first 48 hours
      followed by buccal nitrate (eccentric dose regimen) or placebo during healing
      over 6 weeks postinfarction, indicated that prolonged nitrate therapy effectively
      limited left ventricular remodeling and improved function further compared with
      placebo.

PMID- 8279354
TI  - Early and late angiotensin-converting enzyme inhibition in acute myocardial
      infarction.
AB  - Studies in animals and humans have shown that angiotensin-converting enzyme (ACE)
      inhibitors can prevent or at least attenuate ventricular dilation and remodeling
      following acute myocardial infarction (MI) and can improve subsequent left
      ventricular dysfunction, a strong predictor of survival. The question as to which
      patients will benefit most from ACE inhibitor therapy and the optimal timing of
      administration of such intervention after the onset of symptoms is still matter
      of debate, even if it is hypothesized that a greater benefit in terms of
      remodeling prevention may occur after early administration. However, while it is
      currently accepted that patients with asymptomatic postinfarctual left
      ventricular dysfunction can benefit from long-term administration of an ACE
      inhibitor when therapy is started late, the usefulness of an early administration
      is still to be clarified. In this setting, the question of early versus late ACE
      inhibitor treatment has to be related to the different evolving pattern of
      myocardial infarction with regard to the different degrees of postinfarction
      ventricular dysfunction and neurohormonal activation, whose extent could
      influence the effect of ACE inhibition. For example, not all patients with acute
      MI show progressive ventricular dilation. Early dilation is frequent in patients
      with anterior localization of necrosis, whereas it is usually not relevant in
      patients with acute inferior MI. Thus, different postinfarction patterns may
      differently influence the clinical success of therapeutic interventions, which
      can be instituted at various stages following acute MI.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8279355
TI  - Antithrombotic therapy in the secondary prevention of myocardial infarction.
AB  - There is now convincing evidence that the majority of myocardial infarcts are
      caused by acute occlusion of the coronary artery with a thrombus, often
      originating from a ruptured atherosclerotic plaque. The thrombus is composed of
      both platelets and fibrin, so it is logical to expect that both antiplatelet and
      anticoagulant therapy would be effective for the prevention of reinfarction and
      other thrombotic vascular events following myocardial infarction. A review of
      clinical trials confirms this suggestion. Aspirin is beneficial in that it
      reduces vascular mortality by about 12% and total vascular events by 25%.
      Similarly, oral anticoagulants reduce total mortality by up to 20% and vascular
      events by about 40%. However, relatively few large scale trials of oral
      anticoagulants after infarction have been carried out, and the confidence
      intervals are wider than those for the aspirin trials. In practice aspirin is
      used more widely than oral anticoagulants as it is easier to administer and
      control. Only one trial (EPSIM) has directly compared oral anticoagulants and
      aspirin. This trial showed that both drugs had equal efficacy but that compliance
      with aspirin was better. Finally, the question of giving antiplatelet agents and
      anticoagulants together, to block both platelet aggregation and fibrin formation,
      is considered. A preliminary trial in prosthetic heart-valve patients has been
      encouraging but more large, long-term trials are required before recommendations
      can be made, as the use of both drugs together carries an increased risk of
      severe hemorrhage.

PMID- 8279356
TI  - Expanding indications for thrombolytic therapy in acute myocardial infarction.
      How late is too late, and how early is early: the clinician's view of the first
      100 minutes.
AB  - Proper understanding of the pathologic process of a ruptured plaque followed by
      thrombus formation, with acute assessment of the deranged pathophysiology of the
      coronary circulation as a sequel, remains the basis for rational therapy of
      cardiac ischemia. With the advent of better thrombolytic regimens, improved
      direct reperfusion via angioplasty, and streamlined recognition/admission
      procedures, therapeutic strategies for dealing with acute myocardial infarction
      have once more turned to the options for early therapy. From recent studies of
      out-of-hospital thrombolysis or immediate percutaneous transluminal coronary
      angioplasty, the position is reinforced that "early" means the first 100 minutes.
      It is hoped that the large Global Utilization of Streptokinase and t-PA for
      Occluded Arteries (GUSTO) study, which specifically analyses the effect of early
      reperfusion by optimal alteplase and actilyse (recombinant tissue-type
      plasminogen activator [rt-PA]) versus streptokinase regimens will confirm this
      essential concept once and for all. Thus, when appropriate therapy--depending in
      the local availability of facilities--is promptly given, further reductions in
      myocardial infarction size and ventricular dysfunction can be achieved, resulting
      in mortality rates < 5%, at substantial savings in ever more expensive healthcare
      resources. "Early is < 100 minutes; later may be too late or too costly."

PMID- 8279357
TI  - Use of composite endpoints in thrombolysis trials of acute myocardial infarction.
AB  - Although preventing early mortality following acute myocardial infarction (MI) is
      the most important goal of thrombolytic therapy, insistence on its use as the
      only or principal endpoint in trials of acute MI will limit the number of new
      thrombolytic-antithrombotic regimens that can be tested, and thus may inhibit
      future progress of this important area of cardiovascular therapeutics. Trials of
      thrombolytic therapy over the past decade, as discussed in this article, have
      demonstrated that: (1) thrombolytic therapy improves both mortality and
      intermediate endpoints, and (2) intermediate nonfatal endpoints are strongly
      linked to long-term mortality. Taken together, these facts provide strong
      evidence that intermediate nonfatal events can be used as valid endpoints in
      future trials of thrombolytic therapy. The unsatisfactory outcome composite
      endpoint, which incorporates mortality and important intermediate endpoints, will
      make it possible to compare innovative new regimens in much smaller trials.
      Ultimately, both of these approaches (i.e., megatrials using a mortality endpoint
      and smaller trials utilizing a composite unsatisfactory outcome endpoint) can be
      used in a complementary fashion. A new regimen could first be tested using the
      unsatisfactory outcome endpoint; if it showed particular promise, it could then
      become a candidate for testing in a megatrial. Conversely, if it did not prove
      better than standard regimens, futile research in tens of thousands of patients
      might be prevented. Thus, the use of composite endpoints will expand the number
      of new thrombolytic-antithrombotic regimens that can be tested and, it is hoped,
      accelerate progress in the treatment of acute MI.

PMID- 8279358
TI  - Is there an age limit for thrombolytic therapy?
AB  - Thrombolytic therapy has revolutionized the treatment of acute myocardial
      infarction. The mortality of infarction increases very steeply with increasing
      age > 65 years. One-month mortality in such patients is in the range of 20-30%.
      The proportional benefit of lytic treatment is somewhat less in these older
      patients, but since mortality is high, the absolute benefit is as large or larger
      than that in younger patients. The risks of stroke due to thrombolysis are
      balanced between increased risk of cerebral hemorrhage but decreased risk for
      ischemic/embolic stroke. This trade-off results, overall, in a slightly increased
      stroke rate of about 1-2 per 1,000 nonfatal strokes, but with about 20 fewer
      deaths per 1,000 myocardial infarctions. In addition to these striking mortality
      benefits, there are also important reductions in infarct size, leading to
      decreased morbidity from heart failure or arrhythmias.

PMID- 8279359
TI  - Thrombolysis as an adjunct to angioplasty.
AB  - Acute coronary occlusion following angioplasty is a significant cause of in
      hospital morbidity and mortality. Following acute closure, several strategies can
      be used to reopen the artery, including redilation, adjunctive thrombolysis, or
      other interventional techniques. Definite indications for thrombolysis as an
      adjunct to angioplasty include (1) recently occluded saphenous vein grafts,
      patent native vessels, or saphenous grafts with abundant intracoronary thrombus;
      and (2) acute closure during angioplasty, which is presumably secondary to
      thrombus formation and resistant to redilation alone.

PMID- 8279360
TI  - Validation of the early open infarct vessel hypothesis.
AB  - The insights from the Global Utilization of Streptokinase and t-PA for Occluded
      Arteries (GUSTO) trial have paved the way for further refinement in myocardial
      reperfusion strategies. For the moment, there is a better pharmacologic approach
      for achieving rapid and complete coronary thrombolysis. However, for the future,
      the legacy from this project is much more meaningful, providing clear-cut
      validation of the "early open vessel hypothesis" while at the same time
      exemplifying how deficient our strategies for reperfusion are today. There are
      explicit signals for persistent, meaningful improvement in the years ahead.

PMID- 8279361
TI  - On the future of thrombolytic therapy for acute myocardial infarction.
AB  - The beneficial effects of thrombolytic therapy in acute ischemic coronary
      syndromes, and particularly in acute myocardial infarction, are now well
      established. The limited efficacy and potentially life-threatening side effects
      of currently available thrombolytic agents, however, remain a problem. Available
      evidence suggests that the efficacy of coronary thrombolysis could be augmented
      either by shortening the time to treatment, by improvement of the potency and
      specificity of fibrin-dissolving agents, by optimized conjunctive treatment with
      anticoagulant and antiplatelet agents, or by a combination of all 3. These
      objectives can be pursued by intensified education of the public, paramedical
      personnel, and physicians; development of novel thrombolytic agents; and further
      elucidation of pathophysiologic determinants of recanalization and its
      maintenance. Although it is clear that compounds with antithrombin or
      antiplatelet properties may enhance and sustain the action of thrombolytic
      agents, their optimal use and potential hemorrhagic side effects remain to be
      further explored. Optimized thrombolytic therapy eventually will most likely
      consist of administration of potent specific plasminogen activators in
      combination with conjunctive targeted anticoagulant and/or antiplatelet agents.

PMID- 8279362
TI  - New strategies for enhancing the speed and rate of coronary reperfusion.
AB  - Large, controlled clinical trials have conclusively demonstrated that intravenous
      thrombolytic therapy reduces mortality in patients with acute myocardial
      infarction. The recently published Global Utilization of Streptokinase and t-PA
      for Occluded Arteries (GUSTO) study demonstrated that patency within 90 minutes
      is predictive of survival. As a consequence, the interest in new strategies for
      enhancing the speed and rate of coronary reperfusion has been renewed. Further
      improvements in coronary patency can be anticipated by adopting a variety of
      approaches. Some of these approaches are simple and require only the application
      of proven principles, whereas others are more complex and require further
      research. The first approaches include earlier treatment after the onset of
      clinical symptoms, because of the strong relation between early treatment and
      improved clinical efficacy. Other approaches include development of more
      effective dosage regimens for the available thrombolytic agents, development of
      more fibrin-specific agents in an attempt to speed up lysis, and development of
      safer, more effective adjunctive antithrombotic agents to accelerate thrombolysis
      and prevent rethrombosis. The potential benefits from these latter approaches
      must not be offset by unacceptable increases in major bleeding or in the costs of
      treatment. The application of proven principles to improve coronary reperfusion
      should not be obscured by the research of more effective pharmacologic
      approaches. Actually, earlier and wider use of the currently available
      thrombolytic agents could potentially save more lives than the development of
      technically more exciting new approaches.

PMID- 8279363
TI  - Activation of the hemostatic system during thrombolytic therapy.
AB  - Activation of the hemostatic mechanism has been described during thrombolytic
      therapy. This phenomenon has been detected by new methods of assessing hemostatic
      system function, based on immunoenzymatic or radioimmunoassays. However, these
      methods are extremely sensitive and, unless they are performed in expert
      laboratories, carefully following the recommended procedures, they generate in
      vitro artifacts. A description of these methods is provided, as well as a
      critical review of the available studies. The correct use of these methods will
      provide us with an understanding of the complex response of the hemostatic system
      to pharmacologic thrombolysis.

PMID- 8279364
TI  - Conjunctive antithrombotic therapy for thrombolysis in myocardial infarction.
AB  - Disruption of an atherosclerotic plaque in coronary arteries with a minor
      stenosis is the usual stimulus for acute coronary thrombosis and myocardial
      infarction. In this article the pathogenesis of arterial thrombosis and
      contributions of local arterial wall substrates, the rheology of blood flow,
      systemic factors, and the critical role of thrombin in the formation of thrombus
      are discussed. More potent antithrombotic therapy may accelerate exogenous
      thrombolysis, allows endogenous thrombolysis, and should reduce recurrent
      infarction and ischemia and death, as well as need for coronary
      revascularization. Maximal antithrombotic therapy for acute myocardial infarction
      includes an intravenous bolus of heparin at 100 U/kg followed by an intravenous
      infusion--at 1,200 U/hr for patients weighing 60-80 kg, 1,300 U/hr for those
      weighing > 80 kg, and 1,000 U/hr for those weighing < 60 kg (or 17 U/kg/hr)--to
      maintain the activated partial thromboplastin time at 2-3 times control (60-90
      sec) for at least 5-7 days. To convert intravenous to subcutaneous
      administration, use 14,000-17,000 U every 12 hours and initially overlap the
      intravenous infusion by 2 hours. The loading dose of aspirin on admission to the
      hospital is 160 mg followed by 80 mg/day. High-risk patients should be considered
      for conversion of heparin to warfarin therapy for at least 3 months at an
      international normalized ratio of 2.5-4.0 for the prevention of recurrent
      ischemia, reinfarction, death, thromboembolism, reactivation of thrombosis, and
      reduced necessity for revascularization.

PMID- 8279365
TI  - Noninvasive assessment of reperfusion and reocclusion after thrombolysis in acute
      myocardial infarction.
AB  - The clinical significance of ST-segment changes and of the time course of
      appearance in serum of different cardiac proteins has been reviewed for the
      diagnosis of coronary reperfusion and reocclusion after thrombolysis. In
      particular, the value of serial 12-lead electrocardiographic (ECG) studies, of
      Holter monitoring, and of continuous multilead computer-assisted ECG monitoring
      is compared. Regarding the serum proteins, the clinical significance of
      reperfusion indices described so far for serum creatine kinase (CK), its
      isoenzyme serum creatinine kinase MB, the CK isoforms, and myoglobin is reviewed.
      Emphasis is placed on (1) the calculation method used for deriving the
      reperfusion indices; (2) the sensitivity and the specificity of the reperfusion
      indices; (3) the minimum turn-around time needed to produce the reperfusion
      indices (depending on the practicability of the analytical and calculation
      methods and their applicability in an emergency laboratory); (4) the ability of
      the indices to produce reliable estimates of reperfusion efficacy of the
      thrombolytic agents under study; and (5) the ability of the marker proteins to
      detect reinfarction as well as the suitability of the markers to detect real-time
      necrosis.

PMID- 8279366
TI  - The open artery: beyond myocardial salvage.
AB  - Despite the potential limitations, the available data suggest the importance of
      the open artery as a marker of survival following infarction. Perhaps the most
      important, although as yet unanswered, question is when is it too late to reopen
      an artery? Further, is reperfusion by interventional techniques preferable to
      reperfusion by lytic therapy alone? Although a reduction in mortality has not
      been demonstrated for thrombolysis beyond 12 hours (other than the Second
      International Study of Infarct Survival, ISIS-2), improvements in ventricular
      function (which might translate into a survival benefit) have been demonstrated
      even for very delayed reperfusion. It is hoped that future work will allow us to
      answer better when such therapy might be preferable.

PMID- 8279367
TI  - Left ventricular function after coronary artery reperfusion.
AB  - Left ventricular dysfunction and dilation after reperfusion relate to the amount
      of infarcted and dysfunctional myocardium and will continue to be important
      determinants of morbidity and mortality. There is marked heterogeneity in the
      anatomic and pathophysiologic presentation of patients with acute myocardial
      infarction prior to thrombolysis, and many of these individual settings resemble
      those in animal species with various degrees of collateral formation. Three major
      determinants of infarct size are responsible for this heterogeneity and include
      the risk area, the duration of the coronary occlusion, and the level of the
      residual coronary blood flow via collaterals or a partially patent artery. All 3
      of these determinants will influence the initial and late results of reperfusion
      therapy on infarct size and ventricular function. However, in addition to late or
      unsuccessful thrombolysis, there are other important factors determining outcome:
      inadequate reflow, residual coronary stenosis, and coronary reocclusion, factors
      that can be associated with late progressive left ventricular dilation and
      dysfunction. The risk factors for left ventricular dysfunction and dilation after
      reperfusion can now be identified, and such patients should undergo coronary
      angiography prior to hospital discharge and, if appropriate, revascularization of
      the infarct-related artery (and perhaps other vessels). In other patients, if
      serial studies reveal progressive left ventricular failure and dilation late
      after reperfusion, despite therapy with an angiotensin-converting enzyme (ACE)
      inhibitor, and if repeat coronary angiography identifies significant coronary
      stenoses and areas of hibernating or stunned myocardium, revascularization may
      limit progression of dilation and improve left ventricular function.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279368
TI  - Ventricular remodeling and infarct expansion.
AB  - Infarct expansion, defined as an alteration in the ventricular topography due to
      thinning and lengthening of the infarcted segment, develops within the first few
      hours of the acute symptoms, mostly in patients with a large, transmural,
      anterior myocardial infarction. Shape changes, peculiar to risk region location
      and due to disparity in regional ventricular architecture, could be posited as
      the first step in the process of infarct expansion, with various cellular
      mechanisms contributing to subsequent continued early and late ventricular
      dilation. Because the increase in left ventricular volume is expected to be
      linearly dependent on the extent of the infarction, limiting infarct size, by
      thrombolysis, would proportionally reduce enlargement of the cavity. The effect
      of thrombolysis on left ventricular volume, however, seems not to be completely
      accounted for by the lessening effect of reperfusion on infarct size, because
      data suggest a restraining effect of reperfusion on the process of ventricular
      dilation in addition to the lessening effect on infarct size. If this turns out
      to be true, then the achievement of a patent vessel even beyond the time period
      when that patency may be expected to salvage myocardium would be further
      justified. Theoretical predictions substantiate the potential effectiveness in
      restraining ventricular dilation of stiffening of the necrotic region alone,
      independently of myocardial salvage in infarcted patients. The process of
      progressive ventricular dilation involves not only a primary alteration in
      function of the infarcted region, but also a time-dependent secondary change in
      the noninfarcted tissue itself, finalized to restore stroke volume despite a
      persistently depressed ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279369
TI  - Prognostic value of left ventricular mass in uncomplicated acute myocardial
      infarction and one-vessel coronary artery disease.
AB  - This study assesses the relative prognostic value of increased left ventricular
      (LV) mass compared with residual ischemic myocardium and angiographic
      characteristics of the diseased vessel in 76 patients with uncomplicated acute
      myocardial infarction associated with 1-vessel coronary artery disease (CAD). All
      patients underwent symptom-limited treadmill exercise testing, resting and
      dipyridamole echocardiography and coronary angiography before discharge, and were
      followed-up for 32 +/- 6 months. LV measurements were obtained in diastole
      according to the Penn convention. Measurements of LV mass were divided by body
      surface area to obtain LV mass index. A cut-off value of 135 g/m2 body surface
      area for men and 112 g/m2 for women was prospectively selected. The individual
      effects of clinical, stress testing and angiographic variables were evaluated by
      using the Cox regression model. Echocardiographic LV mass index was increased in
      43 patients and normal in 33. There was no intergroup difference with respect to
      baseline clinical and angiographic variables, ejection fraction and prevalence of
      stress-induced ischemia. During follow-up there were 23 cardiac events in the 43
      patients with increased LV mass index and only 5 in the 33 with normal LV mass
      index (p < 0.001). No patient died or had nonfatal reinfarction among patients
      with normal LV mass. Cox survival analysis identified an increased LV mass index
      as the only independent predictor of cardiac events (chi-square = 7.9; p < 0.005;
      RR = 5.4). Thus, these data suggest that LV mass is an important independent risk
      factor in patients with uncomplicated acute myocardial infarction associated with
      1-vessel CAD.

PMID- 8279370
TI  - Difference between women and men in left ventricular pump function during
      predischarge exercise test after acute myocardial infarction.
AB  - To evaluate the difference in left ventricular (LV) pump function during
      predischarge exercise testing between postmenopausal women and age-matched men
      with myocardial infarction, global and regional ejection fraction, LV end
      diastolic volume, and the ratio of systolic blood pressure to LV end-systolic
      volume were investigated using radionuclide angiography in 25 postmenopausal
      women and 37 age-matched men. There were no significant differences in the
      resting radionuclide angiographic indexes between women and men. Global and
      regional ejection fraction of noninfarcted area, and the ratio of systolic blood
      pressure to LV end-systolic volume decreased at peak exercise in women, but these
      indexes increased in men. Although there was no significant difference in the
      amount of change in LV end-diastolic volume during exercise between the 2 groups,
      the amount of increase in LV end-systolic volume was significantly larger in
      women than in men. The ratio of systolic blood pressure to LV end-systolic volume
      had a curvilinear relation with LV end-diastolic volume at rest and peak
      exercise, but the ratio of systolic blood pressure to LV end-systolic volume was
      larger at any LV end-diastolic volume in men than in women during exercise. Thus,
      lower global ejection fraction and the ratio of systolic blood pressure to LV end
      systolic volume during exercise in postmenopausal women compared with age-matched
      men indicate that gender may have played an important role in the LV remodeling
      process.

PMID- 8279371
TI  - Relation of reperfusion success with anistreplase or alteplase in acute
      myocardial infarction to body weight. The TEAM-3 investigators.
AB  - Adjustment in dose based on body size is not recommended currently for
      thrombolytic regimens, except for a reduction in alteplase (recombinant tissue
      type plasminogen activator [rt-PA]) dose for safety reasons in patients with low
      body weight. It is unresolved how to dose thrombolytic agents in very heavy
      patients. The study objective was to assess whether patency of the infarct
      related artery at 1 day after therapy with anistreplase (anisoylated plasminogen
      streptokinase activator complex [APSAC]) or rt-PA is adversely affected by
      increased body weight. Data were analyzed from a double-blind, randomized,
      comparative study of APSAC (30 U/5 min) versus rt-PA (100 mg/3 hours, adjusted
      downward for body weight < 65 kg), together with heparin and aspirin, in patients
      with acute myocardial infarction presenting within 4 hours of symptom onset.
      Coronary patency, determined at 1 day, was assessed in a blinded fashion, and
      patency success was correlated with body weight, divided into quintiles. In
      patients treated with APSAC, coronary patency rates were similar in those in the
      upper quintile of body weight (> 94 kg; n = 22) and in the low-normal weight
      group (n = 126) (86 and 90%, respectively, for perfusion grade 2/3 [p = 0.64];
      and 82 and 74%, respectively, for grade 3 [p = 0.42]). In contrast, for the rt-PA
      group, heavy patients (n = 34) achieved significantly lower patency rates (74 vs
      89% for grade 2/3 [p = 0.02]; and 59 vs 77% for grade 3 [p = 0.03]). The dose of
      heparin administered, adjusted to maintain a therapeutic partial thromboplastin
      time until the 1-day (mean 28 hours) angiogram, was greater in the heavy than in
      the low-normal weight group (mean +/- SE 39,680 +/- 4,818 vs 30,027 +/- 1,177 U;
      p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279372
TI  - Comparison of nifedipine gastrointestinal therapeutic system and atenolol on
      antianginal efficacies and exercise hemodynamic responses in stable angina
      pectoris.
AB  - A gastrointestinal therapeutic system (GITS) of nifedipine has been developed to
      provide a once-daily dosing, and predictable, relatively constant plasma
      concentrations. This study compared the antianginal efficacy of nifedipine GITS
      with a once-a-day beta-receptor blocker, atenolol. Seventeen patients with
      documented coronary artery disease and stable stress-induced angina pectoris were
      studied during a 2-week, single-blind, placebo baseline phase and a 12-week
      randomized, double-blind, active drug crossover efficacy phase, using the bicycle
      exercise test and ambulatory electrocardiographic recordings. Patients exercised
      significantly longer with nifedipine GITS (883 +/- 47 seconds) and atenolol (908
      +/- 44 seconds) than with placebo (794 +/- 41 seconds). Nifedipine GITS reduced
      systolic blood pressure at all stages of exercise compared with placebo but,
      because heart rate tended to increase more during nifedipine therapy, there was
      no difference in rate-pressure products between the placebo and nifedipine GITS
      periods. In contrast, atenolol reduced heart rate, systolic blood pressure and
      rate-pressure product during exercise compared with placebo. Whereas left
      ventricular ejection fractions (by radionuclide angiocardiography) increased with
      exercise, the maximal increase was smaller with atenolol than with placebo and
      nifedipine. The net increase in left ventricular ejection fraction at the end of
      exercise was greater with nifedipine than with placebo or atenolol. Ambulatory
      electrocardiograms showed only a small number of ischemic events. Neither
      nifedipine GITS nor atenolol reduced the number of ischemic events or total
      duration of ST-segment deviations significantly. It is concluded that nifedipine
      GITS is as effective an antianginal agent as atenolol, but the hemodynamic
      effects of the 2 agents differ.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279373
TI  - Serum triglycerides in the prediction of coronary artery disease (an Italian
      experience).
AB  - An occupational group living in Rome and composed of 3,007 men aged 46 to 65
      years who were free from previous major coronary events was screened for a number
      of coronary risk factors and then followed up for 10 years. In all, 107 coronary
      deaths occurred in 10 years. There was a positive relation between coronary death
      rate and increasing levels of triglycerides, but the difference between the
      extreme quintile classes was not any more significant after adjustment for
      cholesterol levels. A cross-classification involving low-density lipoprotein
      (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride
      levels showed a higher coronary artery disease (CAD) mortality in subjects with a
      higher LDL cholesterol/HDL cholesterol ratio and higher triglycerides. However,
      the excess risk in this subgroup was largely explained by the mean levels of
      total cholesterol. The multivariate proportional-hazards Cox model with coronary
      deaths as the end point, and age and triglycerides as predictors, produced a
      significant coefficient for triglycerides that became nonsignificant when other
      lipids alone or in combination (total, HDL and LDL cholesterol and some of their
      ratio) were fed into the model as further covariates. It is concluded that there
      is no evidence of an independent role of triglycerides in the prediction of
      coronary deaths.

PMID- 8279374
TI  - Circulatory and catecholamine changes during head-up tilt testing in
      neurocardiogenic (vasovagal) syncope.
AB  - Changes in heart rate, arterial pressure, norepinephrine and epinephrine levels
      were compared in 19 consecutive patients (10 men and 9 women, mean age 46 +/- 16
      years) with neurocardiogenic syncope and 11 age- and sex-matched control subjects
      (5 men and 6 women, mean age 49 +/- 15 years) during head-up tilt testing.
      Norepinephrine and epinephrine levels were measured at the baseline supine
      position, in the initial upright position, every 90 seconds during the 70 degrees
      upright tilt, at the time of termination due to hypotension and syncope (or at 15
      minutes in control subjects), and at 40 seconds and 1 minute and 40 seconds in
      the supine position after terminating the head-up tilt test. Baseline
      norepinephrine, epinephrine and heart rate were slightly higher in patients.
      Despite a significant decrease in mean arterial pressure during head-up tilt
      testing in patients (51 +/- 20 mm Hg; p < 0.001), norepinephrine levels in
      patients and control subjects at the time of terminating the head-up tilt test
      were comparable (459 +/- 204 vs 473 +/- 172 pg/ml). A fivefold increase in
      epinephrine levels (73 +/- 53 to 345 +/- 260 pg/ml; p < 0.01) were seen in
      patients, whereas control subjects had insignificant change (38 +/- 16 to 65 +/-
      44 pg/ml). It is concluded that diminished neuronal sympathetic activity and
      enhanced adrenomedullary activity is demonstrated during head-up tilt testing in
      patients with neurocardiogenic syncope.

PMID- 8279375
TI  - Efficacy of adenosine in terminating catecholamine-dependent supraventricular
      tachycardia.
AB  - The purpose of this study was to determine if adenosine is equally effective in
      terminating catecholamine-dependent and independent supraventricular tachycardia
      (SVT). The effect of adenosine on termination of SVT was studied in 21 patients:
      12 with atrioventricular (AV) reciprocating tachycardia, and 9 with AV node
      reentrant tachycardia. Group 1 comprised 13 patients who had SVT induced in the
      absence of exogenous catecholamines, whereas group 2 comprised 8 who needed
      isoproterenol (1.6 +/- 0.4 micrograms/min) for induction. There was no
      statistical difference between the 2 groups regarding age, weight, mean arterial
      pressure during sinus rhythm and SVT, cycle length of SVT, or norepinephrine and
      epinephrine levels during sinus rhythm and SVT. Cycle length during sinus rhythm
      was significantly decreased in group 2. The mean dose of adenosine needed to
      terminate SVT was 52 +/- 6 micrograms/kg of body weight in group 1, and 61 +/- 12
      micrograms/kg in group 2 (p > 0.05). In addition to isoproterenol not altering
      the minimal dose of adenosine necessary to terminate SVT, there was also no
      correlation between the dose of adenosine (mean 55 +/- 6 micrograms/kg) of each
      patient, and the corresponding endogenous epinephrine (273 +/- 59 pg/ml) (r = 
      0.19) and norepinephrine (400 +/- 58 pg/ml) (r = 0.01) levels during SVT, or
      cycle length of SVT (323 +/- 9 ms) (r = -0.35). The results show that adenosine
      is equally effective in terminating catecholamine-dependent and independent SVT;
      higher adenosine doses should not be needed to manage catecholamine-dependent
      SVT.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279376
TI  - Use-dependent properties of flecainide acetate in accessory atrioventricular
      pathways.
AB  - Flecainide acetate has been shown to have use-dependent properties. The use
      dependent properties of flecainide were evaluated in 20 patients (13 men and 7
      women, mean age 32 +/- 11 years) with accessory atrioventricular connections.
      Twenty to 30 stimulus drive trains were introduced in either the atrium or
      ventricle at progressively faster rates. The range of cycle lengths over which
      anterograde and retrograde conduction block occurred in the accessory pathway was
      assessed in the drug-free state and after oral loading with flecainide acetate.
      The block cycle length index was defined as the shortest cycle length during
      which 1:1 conduction was maintained in the accessory pathway minus the longest
      cycle length during which block in the accessory pathway occurred on the second
      paced beat. In the drug-free state, the (mean +/- SD) anterograde and retrograde
      block cycle length indexes were 20 +/- 12 and 20 +/- 9 ms, respectively. After
      flecainide therapy, the anterograde and retrograde block cycle length indexes
      increased to 80 +/- 33 and 65 +/- 29 ms, respectively (p = 0.002 compared with
      the drug-free state). The block cycle length index did not correlate with serum
      flecainide levels, but did correlate with other electrophysiologic markers of
      drug effect on accessory pathway conduction. The change in the block cycle length
      index demonstrates that flecainide has a progressive effect on accessory pathway
      conduction at more rapid rates, consistent with its in vitro use-dependent
      properties. This index is an excellent marker of drug efficacy.

PMID- 8279377
TI  - Characteristics and radiofrequency ablation therapy of intermediate septal
      accessory pathway.
AB  - Fourteen patients (5%) with an intermediate septal accessory pathway were
      identified among 283 consecutive patients with the Wolff-Parkinson-White syndrome
      who had electrophysiologic study and radiofrequency ablation therapy. Nine were
      women and 5 were men (mean age 33 +/- 13 years). The resting electrocardiogram
      showed ventricular preexcitation in 8 patients and normal PR interval in 6.
      Anterograde and retrograde mapping studies revealed that the accessory pathway
      was para-Hisian in 11 patients and paranodal in 3. The accessory pathway was
      successfully ablated in 10 patients (9 para-Hisian and 1 paranodal) and damaged
      in 1 (para-Hisian). Treatment of 3 patients was complicated by transient
      atrioventricular (AV) block, of 1 by intermittent second-degree AV block, and of
      another by permanent complete AV block requiring implantation of a permanent
      pacemaker. Six patients underwent a follow-up electrophysiologic study 84 +/- 55
      days after ablation; none had induction of tachycardia even after isoproterenol
      infusion. It is concluded that radiofrequency ablation therapy for intermediate
      septal accessory pathway is feasible. However, the success rate is only modest
      (71%), whereas complications with heart block (36%) or complete right bundle
      branch block (29%) are high. Thus, the procedure should be reserved for patients
      with life-threatening or troublesome symptomatic tachyarrhythmias.

PMID- 8279378
TI  - Cardiac size and function during adrenocorticotropic hormone-induced systolic
      systemic hypertension in infants.
AB  - The effects of adrenocorticotropic hormone (ACTH) on systolic blood pressure, and
      echocardiographic indexes of heart size and function were investigated in 14
      infants. After 25 days (range 13 to 46) of treatment with ACTH, systolic blood
      pressure increased from 93 +/- 9 to 118 +/- 20 mm Hg (p < 0.001; mean +/- 1 SD).
      Systolic hypertension (systolic blood pressure greater than the 95th percentile
      for age) developed in 10 of 14 infants and was associated with an increase in
      left ventricular (LV) shortening fraction from 41 +/- 5% to 52 +/- 8% (p <
      0.001). Myocardial hypertrophy and an increase in echocardiographic indexes of
      myocardial contractility were observed also. To assess the temporal relation
      between the onset of systolic hypertension and these cardiac changes, data from 8
      infants with serial echocardiograms and blood pressure determinations were
      examined. After a mean 14 days (range 8 to 18) of ACTH, LV shortening fraction
      increased from 39 +/- 6% to 53 +/- 8% (p < 0.01), whereas systolic blood pressure
      remained normal in 7 of 8 infants. In addition, a decrease in LV end-systolic
      dimension was observed during this early phase. This report documents myocardial
      changes in individual patients, which occur before and during the development of
      systolic hypertension.

PMID- 8279379
TI  - Systolic time intervals after phenylephrine administration for early
      stratification of patients after acute myocardial infarction.
AB  - This study was designed to assess the usefulness of the changes in left
      ventricular (LV) systolic time intervals after phenylephrine administration for
      detecting high-risk patients soon after acute myocardial infarction by
      correlation with the angiographic and ventriculographic findings. The procedure
      was performed in 76 consecutive patients (group I) on the fourth postinfarction
      day and in 12 normal subjects (group II) free of coronary artery disease. In 20
      patients with LV ejection fraction < or = 40% (subgroup IA) the preejection
      period (PEP)/LV ejection time (ET) ratio increased from 0.410 +/- 0.107 to 0.535
      +/- 0.102 (p = 0.01) after phenylephrine, whereas in the remaining 56 patients
      (subgroup IB) with LV ejection fraction > 40% and in the 12 normal subjects the
      PEP/LVET increased nonsignificantly. Of patients with LV ejection fraction > 40%
      a subset of 20 patients was distinguished with proximal stenosis in both left
      anterior descending and either a dominant right or left circumflex coronary
      artery (subset IB-a). In these the PEP/LVET increased from 0.347 +/- 0.056 to
      0.445 +/- 0.019 (p = 0.0001) after phenylephrine, whereas in the remaining 36
      patients (subset IB-b) without proximal lesions in 2 main arteries the PEP/LVET
      increased nonsignificantly. In conclusion, the PEP/LVET response to phenylephrine
      administration early after acute myocardial infarction is a precise, safe,
      noninvasive bedside method for early stratification of these patients.

PMID- 8279380
TI  - Frequency, cause and effect on operative outcome of depressed left ventricular
      ejection fraction in mitral stenosis.
AB  - To assess the incidence, pathophysiology and influence on operative outcome of a
      depressed left ventricular (LV) ejection fraction (EF) in patients with mitral
      stenosis (MS), demographic, hemodynamic and cineangiographic data on 72 patients
      (16 men, 56 women, aged 19 to 75 years) with isolated MS were reviewed. Of the 45
      who had mitral commissurotomy or replacement, operative course and functional
      class before and after surgery were assessed. Of the 72 patients, 21 (29%) had an
      LVEF < or = 0.50. These 21 were similar to the 51 with an LVEF > 0.50 in age,
      gender, heart rate, intracardiac pressures, transvalvular gradient and valve
      area, but they had larger LV end-diastolic (79 +/- 19 [mean +/- SD] vs 59 +/- 15
      ml/m2, p < 0.001) and end-systolic volumes (46 +/- 13 vs 23 +/- 8 ml/m2, p <
      0.0001). Of the 45 subjects undergoing surgery, operative outcome was similar in
      the 14 with a depressed and the 31 with a normal LVEF. Thus, about 1/3 of
      patients with isolated MS have a depressed LVEF. Compared with those with MS and
      a normal LVEF, these subjects have hemodynamic derangements of similar severity,
      but they have larger LV end-diastolic and end-systolic volumes, suggesting that
      impaired LV contractile function or excessive afterload (rather than diastolic
      underfilling), or both, is the cause of a low LVEF. Those with an LVEF < or =
      0.50 who undergo valve surgery have a similar operative outcome as those with an
      LVEF > 0.50.

PMID- 8279381
TI  - Relation of impaired left ventricular function in mitral regurgitation to left
      ventricular contractile state after mitral valve replacement.
AB  - To reevaluate the postoperative contractile state and survival, 34 patients (19
      men and 15 women; average age 45 years, range 23 to 65) undergoing conventional
      mitral valve replacement between 1980 and 1990 were studied. There were 5 cardiac
      deaths (2 early and 3 late). Four of 5 deaths occurred in patients who had a
      preoperative left ventricular end-systolic volume index > 100 ml/m2. Sixteen
      patients with an end-systolic volume index < 100 ml/m2 (group I), and 5 with an
      index > 100 ml/m2 (group II) underwent repeat catheterization 8 months (range 4
      to 17) after surgery. The ratio of end-systolic wall stress to end-systolic
      volume index increased significantly after surgery in group I, whereas it
      remained reduced in group II. The postoperative end-systolic wall stress/volume
      index ratio correlated significantly with the preoperative end-systolic volume
      index (p < 0.001). In the relation between end-systolic wall stress and ejection
      fraction, all patients in group II had values that were less than the 95%
      confidence limits for the normal relation. In conclusion, patients with a
      preoperative end-systolic volume index > 100 ml/m2 appeared to be at high risk of
      incurring irreversible depressed myocardial contractility, with a high
      postoperative mortality.

PMID- 8279382
TI  - Efficacy and safety of repeated boluses of urokinase in the treatment of deep
      venous thrombosis.
AB  - The only Food and Drug Administration-approved thrombolytic regimen for treatment
      of deep venous thrombosis (DVT) is a 24- to 72-hour continuous infusion of
      intravenous streptokinase. This approach to DVT thrombolysis is not entirely
      satisfactory because of the bleeding complications that may accompany this
      therapy. In the current study, we treated 27 patients with DVT with a novel
      dosing regimen of urokinase: 1,000,000 U administered as a 10-minute bolus, with
      a total of 3 boluses given over approximately 24 hours. Patients were given
      heparin overnight between bolus urokinase doses. Efficacy was assessed by
      comparing baseline and prehospital discharge vascular imaging studies, which
      constituted either venous ultrasound or contrast venography. A vascular-imaging
      panel of physicians, unaware of the sequence of paired studies, found that 14
      patients (52%) had clot lysis (6 slight, 6 moderate and 2 marked), 9 (33%) had no
      change, and 4 (15%) had more extensive thrombosis after treatment (1 slight, 2
      moderate and 1 marked). There were no bleeding complications. At 48 hours after
      starting urokinase, mean plasma fibrinogen levels had decreased 61% from
      baseline, and the mean bleeding time had increased 28% from baseline (but
      remained within the normal range). Because of the promising efficacy and safety
      that were found in this case series, it is concluded that further testing of
      bolus urokinase is warranted against anticoagulation alone.

PMID- 8279383
TI  - Low blood total cholesterol and mortality: causality, consequence and
      confounders.

PMID- 8279384
TI  - Relief of rheumatic mitral stenosis--when and how?

PMID- 8279385
TI  - Out-of-hospital sudden death from left ventricular free wall rupture during acute
      myocardial infarction as the first and only manifestation of atherosclerotic
      coronary artery disease.

PMID- 8279386
TI  - Absence of pharmacokinetic interaction between amiodarone and lidocaine.

PMID- 8279387
TI  - Vasovagal reactions in the cardiac catheterization laboratory.

PMID- 8279388
TI  - Twenty-four-hour energy expenditure and substrate utilization in body builders.
AB  - Twenty-four--hour energy expenditure (EE) was measured by indirect calorimetry in
      10 body builders and 10 lean control subjects of the same sex with similar age,
      height, and percent body fat. The study was performed to elucidate possible
      effects of strength training on energy metabolism and substrate utilization.
      Twenty-four--hour EE was higher in the body builders than in control subjects but
      was similar when adjusted for differences in fat-free mass. A higher 24-h
      nonprotein respiratory quotient (RQ) was found in the body builders. Because both
      groups were in energy balance, the higher RQ in the body builders can be
      attributed to a different habitual diet or may be explained by physiological
      differences.

PMID- 8279389
TI  - Blood pressure and blood lipids among vegetarian, semivegetarian, and
      nonvegetarian African Americans.
AB  - Blood pressure (BP) and serum lipids were compared among three dietary groups of
      Seventh-day Adventist (SDA) African-American adults: vegetarians (VEGs: no
      consumption of animal flesh, n = 66), semivegetarians (SEMIVEGs: one to three
      servings of animal flesh per week, n = 56), and nonvegetarians (NONVEGs: daily
      consumption of animal flesh, n = 45). VEGs had a lower mean waist-to-hip ratio
      (WHR) and lower dietary intakes of protein, saturated fat, and cholesterol
      compared with the NONVEGs. Only 16% of the VEGs were confirmed to be hypertensive
      compared with 35.7% of the SEMIVEGs and 31.1% of the NONVEGs. Independent of
      differences in WHR, the VEGs had significantly lower concentrations of serum
      total cholesterol (STC), LDL-C, triglycerides, STC/HDL-C, and LDL-C/HDL-C than
      the NONVEGs. The SEMIVEGs had lipid values intermediate to the VEG and NONVEG
      groups. Among African-American SDAs, a vegetarian diet is associated with lower
      cardiovascular disease risk factors than is an omnivorous diet.

PMID- 8279390
TI  - Relationship between dietary vitamin C intake and pulmonary function in the First
      National Health and Nutrition Examination Survey (NHANES I).
AB  - We assessed the relationship between dietary vitamin C intake and the level of
      pulmonary function (forced expiratory volume in 1 s, FEV1) in 2526 adults seen as
      part of the first National Health and Nutrition Examination Survey (NHANES I)
      between 1971 and 1974. Multiple-linear-regression analysis was performed with in
      FEV1 as the dependent variable. After age, height, body mass index, race, sex,
      cigarette smoking, and employment status were controlled for, dietary vitamin C
      intake was positively and significantly associated with the level of FEV1 (beta =
      0.00132, P = 0.01). Interaction terms for vitamin C intake and smoking and
      vitamin C intake and respiratory disease were not significant. These data are
      consistent with the hypothesis that vitamin C intake has a protective effect on
      pulmonary function.

PMID- 8279391
TI  - Lipid-lowering diets enriched with monounsaturated or polyunsaturated fatty acids
      but low in saturated fatty acids have similar effects on serum lipid
      concentrations in hyperlipidemic patients.
AB  - The aim of this study was to compare the effects of a diet enriched with
      monounsaturated (MUFAs) with one enriched with polyunsaturated (PUFAs) fatty
      acids on the serum lipoprotein composition in patients with hyperlipidemia. A new
      model for conducting controlled dietary treatment studies in free-living
      hyperlipidemic patients was tested. Twenty-six patients with an average age of 51
      y participated in a crossover study during two consecutive 3.5-wk treatment
      periods. The mean serum cholesterol and LDL cholesterol decreased by 17% and 19%,
      respectively, on the MUFA diet. The corresponding figures on the PUFA diet were
      19% and 23%, respectively. The HDL-cholesterol concentration was significantly
      decreased after both dietary periods. No significant differences in any of the
      variables studied were found between the diets. It is concluded that MUFAs and
      PUFAs, within a diet with a restricted content of saturated fat and total fat,
      are interchangeable with regard to lipid-lowering effects among free-living
      hyperlipidemic patients.

PMID- 8279392
TI  - Body composition of children with cystic fibrosis with mild clinical
      manifestations compared with normal children.
AB  - Because growth and anthropometric measurements are frequently below normal in
      patients with cystic fibrosis (CF), the body composition of 23 children (6-9 y of
      age) who had mild manifestations of CF was examined and compared with a control
      group of 24 subjects similar in age, sex, and weight. Skinfold measurements,
      total body water (TBW) by deuterium oxide dilution, and total body
      electroconductivity (TOBEC) were measured. Skinfold and TBW measurements
      demonstrated that fat mass and fat-free mass did not differ significantly between
      the two groups. No significant difference in percent body fat was found by using
      the skinfold equations of Slaughter et al (13.8% vs 15.3%), although percent body
      fat (TBW method) differed between the groups (P < 0.05). TOBEC measurements (CF,
      n = 14) were not used in the group comparison. The majority of the methods
      demonstrated that the CF group achieved normal growth and body composition, with
      a possible trend of fat depletion.

PMID- 8279393
TI  - Nurses need nutrition education too.

PMID- 8279394
TI  - Effect of habitual exercise on daily energy expenditure and metabolic rate during
      standardized activity.
AB  - To assess whether long-term habitual exercise affects energy expenditure even on
      a nontraining day, 24-h energy expenditure (24-h EE) and metabolic rate of
      sedentary, moderately active, and highly active males (n = 10 per matched group),
      were measured in a room respirometer on two separate occasions: sedentary and
      standardized mild-exercise protocols. Twenty-four--hour EE was greatest in the
      highly active group, second highest in the moderately active group, and lowest in
      the sedentary group on both experimental days (sedentary day: 9908 +/- 344, 9328
      +/- 357, and 8669 +/- 227 kJ/d; exercise day: 11915 +/- 395, 11609 +/- 328, and
      11063 +/- 370 kJ/d, respectively). Differences were significant between the 24-h
      EE (P < 0.01), waking (P < 0.03), and sleeping metabolic rate (P < 0.01) of the
      highly active group compared with the sedentary group. However, when expressed
      per unit lean body mass (LBM), group values on both experimental days were not
      significantly different. Therefore, we found no evidence that habitual exercise,
      at a high or moderate level, leads to a significant prolonged stimulation of
      metabolic rate per unit active tissue. However, the increased LBM associated with
      exercise does increase daily energy expenditure by 8-14%.

PMID- 8279395
TI  - Biological variation in iron-status indexes in elderly women.

PMID- 8279396
TI  - Prophylactic vitamin C: misplaced zeal.

PMID- 8279397
TI  - Variation of the basal metabolic rate and dietary energy intake of Colombian
      women during 1 y.
AB  - Anthropometry, basal and resting metabolic rates (BMR and RMR), and dietary
      energy intake were measured on five occasions approximately 3 mo apart for 1 y in
      21 nonpregnant, non-lactating women 20-42 y of age living under deprived economic
      conditions in Cali, Colombia. There was a significant increase in body weight (1
      1.5 kg) because of increased body fat during the last two rounds of measurement.
      BMR was elevated in the first round but fell to stable values that did not vary
      significantly from 3 to 12 mo. The intraindividual CV of BMR was 8.3% whereas the
      intraindividual CV of dietary energy intake was 17%. Measured BMR was closely
      related to the BMR estimates provided by the empirical equations of Schofield,
      but significantly higher than estimates from the equations of Henry and Rees. RMR
      BMR ratios were very close to those published by FAO/WHO/UNU. Autocorrelation
      analysis of BMR showed weak ability to predict subsequent variation of BMR over
      time and is consistent with random variation of the data.

PMID- 8279398
TI  - Resting metabolic rate before exercise vs a control day.
AB  - Investigations on resting and recovery metabolism have used both preexercise and
      separate control-day measurements as a baseline for comparisons. The purpose of
      this study was to compare preexercise resting data with nonexercise control-day
      resting data. Seven active men aged 25 +/- 5 y and weighing 83.2 +/- 15.4 kg
      followed prescribed dietary (12-h fast) and activity (48-h abstinence)
      preparatory protocols and were scheduled to exercise for 60 min on three separate
      occasions. A fourth session involved no exercise (control) and included an
      extended rest period. Resting metabolic rate (RMR) and heart rate measured in a
      semirecumbent position were not significantly different among preexercise and
      control conditions. Respiratory exchange ratio (RER) increased as the control
      rest was extended to 120 min. Reliabilities for both RMR and RER were initially
      high but were decreased at the end of the extended rest. These results suggest
      that preexercise RMR data can be used as a baseline for comparison purposes. In
      addition, prolonging the rest period does not appear to improve the RMR or RER
      values.

PMID- 8279400
TI  - Effect of lactation on resting metabolic rate and on diet- and work-induced
      thermogenesis.
AB  - Energy metabolism was measured in 24 women before pregnancy and during lactation
      (2 mo postpartum). Resting metabolic rate (RMR) increased by 0.17 +/- 0.38 kJ/min
      and postprandial metabolic rate (PPMR) showed a similar increase (0.17 +/- 0.45
      kJ/min). Thus, the thermic effect of the meal (PPMR minus RMR) was not affected
      by lactation. Between subjects, the lactation-induced increase in RMR appeared to
      be positively related to body weight. During lactation gross metabolic rates
      during cycling (CMR) were slightly reduced and net metabolic rates during cycling
      (CMR minus RMR) tended to decrease by 0.6 kJ/min at all workloads; however, the
      decrease was statistically significant only at the lowest workload. Changes in
      metabolic rate during the recovery period after exercise were not significant,
      but resembled changes in RMR rather than changes in CMR. We conclude that no
      major changes in metabolic efficiency occurred during lactation.

PMID- 8279399
TI  - Effects of dietary intakes on plasma lipids, lipoproteins, and apolipoproteins in
      free-living elderly men and women.
AB  - Plasma lipid and apolipoprotein (apo) A-I and B concentrations and habitual
      dietary intakes were determined in 306 free-living elderly individuals (119 men
      and 187 women, age range 60-100 y). Plasma lipid and apo A-I concentrations were
      significantly higher in women than in men. In older men, plasma triglyceride,
      total cholesterol, and apo B concentrations were significantly lower than in
      younger men, whereas a significant trend towards lower LDL-cholesterol
      concentrations was observed in older women. Energy intake and percent
      macronutrient intake were not influenced by age. Higher carbohydrate intake was
      associated with lower HDL cholesterol and apo A-I concentrations, whereas higher
      total fat intake was associated with higher apo A-I concentrations. Higher
      vitamin A intake was associated with higher plasma concentrations of HDL
      cholesterol and apo A-I. Our data indicate that both dietary and plasma
      concentrations of vitamin A, body mass index, age, and sex are important
      determinants of plasma lipid concentrations in the elderly.

PMID- 8279401
TI  - Cholesterol absorption and excretion in ileostomy subjects on high- and low
      dietary-cholesterol intakes.
AB  - Six healthy ileostomy subjects were given [3H]cholesterol and [14C]beta
      sitosterol in a single meal together with two controlled diets containing 150 or
      450 mg cholesterol/d. Each diet was eaten for 3 d. Cholesterol absorption and
      excretion of cholesterol, bile acids, fat, energy, and nitrogen were analyzed.
      Fractional cholesterol absorption increased from 44 +/- 2.6% (mean +/- SE) to 61
      +/- 3.4% (P < 0.05), but absolute cholesterol absorption decreased from 191 +/-
      11 to 94 +/- 9 mg/d (P < 0.05) on low cholesterol intake compared with high
      cholesterol intake. Weight of ileostomy effluent, or excretion of energy,
      nitrogen, fat, and bile acids did not differ between periods. Endogenous
      cholesterol excretion remained unchanged whereas net cholesterol excretion
      (output minus intake) was 37% higher (P < 0.05) on low compared with high
      cholesterol intake.

PMID- 8279402
TI  - Changes in body composition of malnourished children after dietary
      supplementation as measured by bioelectrical impedance.
AB  - Body composition was measured with bioelectrical impedance in 35 malnourished
      children aged 24-59 mo to investigate the effect of a 3-wk feeding
      supplementation. Twenty children received a high-protein diet with 15% of total
      energy as protein, whereas 15 children received an isoenergetic standard-protein
      diet with 7.5% of energy as protein. Bioelectrical impedance analysis and
      anthropometry were done before and after 21 d of dietary supplementation. The
      children fed the high-protein diet gained significantly more body weight than
      those receiving the standard-protein diet (1.33 +/- 0.54 vs 0.88 +/- 0.47 kg, P <
      0.02). The total body water and fat-free mass determined by bioelectrical
      impedance analysis showed that the group fed the high-protein diet increased
      significantly more (0.92 vs 0.58 kg) than those on the standard-protein diet (P <
      0.02). Results of this study suggest that feeding a high-protein diet accelerates
      catch-up growth and restores the reference body composition in children
      recovering from malnutrition.

PMID- 8279403
TI  - Immediate metabolic availability of dietary fat in combination with carbohydrate.
AB  - We tested the hypothesis that when fat is ingested in combination with
      carbohydrate, direct release of fatty acids into the plasma may occur. Eight
      normal subjects ingested two meals: high-fat (80 g fat, 80 g carbohydrate, and 18
      g protein) and low-fat (< 1 g fat, otherwise closely matched). Over the
      subsequent 6 h, net fat oxidation was greater after the high-fat meal (20.7 vs
      10.6 g, P < 0.01). Plasma nonesterified fatty acid (NEFA) concentrations were
      markedly suppressed after the low-fat meal, but relatively maintained after the
      high-fat meal (P < 0.01). The profile of plasma NEFAs changed after the high-fat
      meal, consistent with entry of meal-derived fatty acids into the NEFA pool. We
      suggest that after ingestion of combinations of carbohydrate and fat, the action
      of lipoprotein lipase on chylomicron-triacylglycerol leads to direct release of
      fatty acids into the plasma and increased fat oxidation.

PMID- 8279404
TI  - Fatty acid-mediated effects on the glutathione redox cycle in cultured
      endothelial cells.
AB  - Endothelial barrier dysfunction after exposure to fatty acids may be mediated by
      disturbances in antioxidant protection. To evaluate this hypothesis, components
      of the glutathione redox cycle such as total, reduced, and oxidized glutathione
      and glutathione reductase and peroxidase were measured in cultured porcine
      endothelial cells exposed to 90 mumol/L of stearic acid (18:0), oleic acid (18:1
      omega-9), linoleic acid (18:2 omega-6), linolenic acid (18:3 omega-3), and/or
      buthionine sulfoximine (BSO). Treatment with fatty acids caused an initial
      decrease in glutathione concentrations, which was followed by an increase at
      later time points. The most marked changes in glutathione redox cycle components
      were induced by 18:2. BSO increased susceptibility of fatty acid-mediated injury
      to endothelial monolayers. The results indicate a fundamental role of the
      glutathione redox cycle in protection against fatty acid-mediated injury to the
      vascular endothelium.

PMID- 8279405
TI  - Lipid profiles after the daily consumption of an oat-based cereal: a controlled
      crossover trial.
AB  - Water-soluble fiber has been reported to reduce serum cholesterol and
      consequently, oat bran, which has a high soluble-fiber content, has been
      recommended as part of a lipid-lowering diet. However, a recent small study of 20
      volunteers with low mean serum cholesterol concentrations (4.8 mmol/L)
      demonstrated no lipid-lowering effect of oat bran. The present study investigated
      64 volunteers with cholesterol concentrations much more typical of the UK
      population (6 mmol/L). Subjects were randomly allocated to receive either a
      normal-sized helping of an oat-based cereal or a cereal containing no oats for 4
      wk and then crossed over to the alternative regimen for a further 4 wk. Small
      (2.23% and 4.55%) but significant (P < 0.04 and P < 0.05) reductions in total and
      low-density-lipoprotein cholesterol, respectively, were observed in association
      with the consumption of oat-based cereal. These data support the view that
      consumption of oat-based cereals may well contribute usefully to a lipid-lowering
      diet.

PMID- 8279406
TI  - Amino acid losses in ileostomy fluid on a protein-free diet.
AB  - The contribution of losses via the gastrointestinal tract to maintenance amino
      acid requirements was assessed by collecting the ileostomy fluid of volunteers
      given a protein-free diet for 5 d. The subjects were eight adult men and women
      with terminal ileum ileostomies after ulcerative colitis. Four consecutive 24-h
      collections of both digesta and urine were made. On the last 2 d an antibiotic
      was given that suppressed microbial activity in the digesta and slightly reduced
      ileostomy outflow. Mean daily amino acid excretion in ileostomy fluid ranged from
      32 mg/d for methionine to approximately 330 mg/d for aspartate and glutamate.
      These losses were compared with current international estimates of amino acid
      requirements. For most essential amino acids gastrointestinal losses accounted
      for 14-33% of daily maintenance requirements but for threonine the contribution
      was 61%.

PMID- 8279407
TI  - Effect of lactic acid bacteria on the intestinal production of lactate and short
      chain fatty acids, and the absorption of lactose.
AB  - The characteristic fermentation pattern seen with specific saccharides in
      incubations with pure cultures of Lactobacillus acidophilus and Bifidobacterium
      bifidum disappeared when incubated in 16.7% fecal homogenate. The productions of
      lactate and short-chain fatty acids in mixed bacterial-fecal incubations were
      similar to productions in fecal homogenates without L acidophilus and B bifidum
      and were mainly associated with the specific mono-, di-, and polysaccharides
      added to the incubate. B bifidum was cultured from ileostomic contents in eight
      of nine ileostomists after oral administration (2.4 x 10(10) cells), but did not
      influence the concentrations and productions of DL-lactate and short-chain fatty
      acids in the ileostomic outputs and incubates. Large amounts of ingested lactic
      acid bacteria (4.2 x 10(10) cells) did not ameliorate lactose malabsorption
      measured by the breath-hydrogen test in 12 lactose malabsorbers. This study shows
      that ingested lactic acid bacteria are indeed present in the colon, but it does
      not support the theory that they change the pattern of colonic fermentation or
      the degree of intestinal lactose malabsorption.

PMID- 8279408
TI  - Contributions of vitamin D intake and seasonal sunlight exposure to plasma 25
      hydroxyvitamin D concentration in elderly women.
AB  - We investigated the contributions (1.00-8.03 micrograms/d, or 40-321 IU/d) of
      vitamin D intake and seasonal sunlight exposure to plasma 25(OH)D in 59 healthy
      women aged 70-97 y with a mean total vitamin D intake of 8.58 micrograms/d (343
      IU/d). In the summer and winter, each subject had a fasting blood measurement and
      assessments of vitamin D intake and sunlight exposure. Vitamin D intake was
      significantly correlated with plasma 25(OH)D in the summer (r = 0.52, P < 0.01)
      and winter (r = 0.63, P < 0.01). The influence of sunlight exposure measured in
      the summer on the 25(OH)D concentration was dependent on the vitamin D intake. In
      subjects with lower vitamin D intakes (1.00-8.03 micrograms/d, or 40-321 IU/d),
      the wintertime 25(OH)D concentrations of those with low and high sunlight
      exposure were comparable. In subjects with higher vitamin D intakes (11.15-28.68
      micrograms/d, or 446-1147 IU/d), however, the wintertime 25(OH)D concentrations
      of those with high sunlight exposure were lower than those with lower exposure
      [63.8 +/- 3.9 and 80.6 +/- 6.7 nmol/L, respectively, P = 0.066; P (intake by
      exposure interaction) < 0.05]. This suggests that the contribution of vitamin D
      intake to plasma 25(OH)D concentration may be influenced by sunlight exposure.

PMID- 8279409
TI  - Effect of guar gum on hunger and satiety after meals of differing fat content:
      relationship with gastric emptying.
AB  - To determine whether the satiating effects of fiber are due to delaying gastric
      emptying or slowing absorption of meals, 3% guar gum was added to high- and low
      fat soups and gastric emptying rate, hunger, and satiety were measured in eight
      male volunteers. Guar gum delayed the emptying of the low-fat soup but the small
      delays in the return of hunger and decline of fullness were significantly
      correlated with the gastric emptying, suggesting mediation by gastric
      mechanoreceptors. The high-fat soup also emptied more slowly but this had no
      effect on the return of hunger or the decline in fullness. The delays in the
      return of hunger and decline of fullness were far greater when guar gum was added
      to the fatty soup; these delays were not correlated with the small additional
      delay in gastric emptying. This is more compatible with slowed absorption and
      prolonged contact of nutrients with intestinal chemoreceptors.

PMID- 8279410
TI  - Restrained eating and ovulatory disturbances: possible implications for bone
      health.
AB  - We assessed the relationship between dietary restraint and menstrual cycle
      characteristics in 27 ovulatory women, previous participants in a longitudinal
      study of spinal cancellous bone mineral density (BMD). Subjects completed the
      restraint scale of the Three Factor Eating Questionnaire, recorded basal
      temperature and exercise for at least three menstrual cycles, and completed a 3-d
      food record. Cycle lengths of women in the upper and lower tertiles of scores for
      restraint were similar [27.8 +/- 1.0 (mean +/- SE) vs 27.6 +/- 0.8 d], but luteal
      phase length was shorter in the former group (8.6 +/- 0.9 vs 10.8 +/- 0.5 d, P <
      0.05). Age, body mass index, percent body fat, waist-hip ratio, reported energy
      intake, and activity were similar between groups. Because the previous
      longitudinal study found associations between ovulatory disturbances and bone
      loss, we assessed spinal BMD using dual-energy x-ray absorptiometry (DXA) and
      quantitative computed tomography (QCT). BMD of women in upper and lower restraint
      tertiles, respectively, did not differ: DXA, 1.15 +/- 0.05 vs 1.20 +/- 0.06
      g/cm2; and QCT, 140 +/- 7 vs 133 +/- 7 mg/cm3. Additional prospective studies,
      however, appear warranted. In conclusion, this study's results provide evidence
      that high dietary restraint is associated with a shortened luteal phase length.

PMID- 8279411
TI  - Protein repletion and treatment in anorexia nervosa.
AB  - Body fat and total body nitrogen (TBN) were quantified before and after refeeding
      in 32 female anorexia nervosa patients and in 29 matched control subjects by
      using the techniques of anthropometry and in vivo neutron-capture analysis
      (IVNCA). Mean body weight of patients (mean body mass index; BMI, in kg/m2), 15.4
      +/- 1.3, was 72.7% of that of control subjects, increasing to 89.8% of mean
      weight of control subjects after refeeding (mean BMI 19.0 +/- 1.2). Mean BMI of
      control subjects was 21.6 +/- 2.7. Compared with the control group, patients'
      nitrogen was initially depleted by 24.5%, increased by 18.4%, but remained 10.6%
      below control values (P < 0.001). Body fat was depleted by 58.4%, increased by
      89.7%, but remained 21.8% below control values (P < 0.001). Thus, despite a
      greater initial depletion and subsequently a greater net gain, body fat remained
      relatively more depleted after treatment than did nitrogen and protein. Anorexia
      nervosa patients were shown to readily replenish protein during nutritional
      rehabilitation.

PMID- 8279412
TI  - Rationale for an international conference series on dietary assessment methods.
AB  - The rationale for establishing an international conference series on dietary
      assessment methods is based on the needs expressed by numerous national and
      international organizations for better methods of collecting and analyzing
      dietary data. Dietary assessment is essential for investigating diet-health
      relationships, formulating policies to reduce health risks, predicting the
      adequacy of the food supply, and monitoring trends in food use, exposure to
      contaminants, and compliance with dietary guidelines. The conference rationale is
      discussed with respect to 1) the need for improved methods to enhance our
      understanding of diet-health relationships, 2) the need for better methods to
      facilitate development and monitoring of nutrition-related health objectives, and
      3) the importance of international participation. Improved methods for assessing
      food intakes will enhance our understanding of the role of diet in the etiology
      and prevention of disease and will facilitate the development of nutrition policy
      and programs leading to improved health worldwide.

PMID- 8279413
TI  - Assessing diets to improve world health: nutritional research on disease
      causation in populations.
AB  - Dietary assessment plays a crucial role in our ability to detect relationships
      between dietary exposure and disease causation. Nutritional problems are at the
      root of major mass diseases that are impediments to progress toward national and
      international health goals. This is true for chronic undernutrition and famine as
      well as many of the chronic diseases afflicting middle-aged and elderly people in
      industrialized and developing countries. High-quality dietary assessment provides
      a sound scientific foundation for the primary prevention of mass diseases,
      whereas inadequate assessment can produce false-negative results and result in
      apparent inconsistencies between cross-population and within-population findings
      for a particular disease. The critical role of dietary assessment in the
      elucidation of disease causation is discussed with regard to high blood pressure,
      heart disease, breast cancer, and several other major chronic diseases. Improved
      approaches to dietary assessment need to be made more widely known, not only
      among research scientists and health practitioners, but also among policymakers
      who require high-quality dietary data for establishing nutrition goals and making
      policy decisions.

PMID- 8279414
TI  - Gaps in dietary-survey methodology in eastern Europe.
AB  - The purpose of this paper is to summarize some methodological problems with
      nutrition surveys in Eastern European countries. A brief review of the literature
      was conducted and a questionnaire was sent to a sample of researchers regarding
      dietary assessment methods used, technical aspects of data collection, and data
      analysis. The findings suggest that despite considerable work and effort devoted
      to nutrition surveys, little information exists on current food and nutrient
      consumption by individuals, either from total population studies or from studies
      of subgroups within the population. Furthermore, there is a lack of uniformity in
      calculating nutritive values of consumed foods with respect to quantification of
      amounts, accounting for differences in food-preparation methods and percentage of
      losses in recipes. These findings indicate a need for standardization, both
      within and between countries, for all types of dietary assessment methods.

PMID- 8279415
TI  - Gaps in dietary-survey methodology in Western Europe.
AB  - A national nutrition monitoring system, including regular dietary surveys of
      representative population samples exists in only a few Western European
      countries. Even though large surveys are carried out sporadically in most
      countries, variability in their objectives, population samples, methodology, and
      reporting limit their comparability. There are two main ways of building a survey
      program: either in connection with health status surveys or in connection with
      household budget surveys. Household budget surveys are the only possibility in
      many countries. However, the data collection method has to be modified from food
      purchase recording to include proper description of all foods consumed by
      individuals during a certain time period. Comparability of food-composition data
      in software systems for nutrient conversion is another problem area.

PMID- 8279416
TI  - Assessment of the US diet in national nutrition surveys: national collaborative
      efforts and NHANES.
AB  - The National Nutrition Monitoring and Related Research Program includes
      conducting national surveys to estimate the dietary intake and nutritional status
      of the US population. As part of this program, a 10-y comprehensive plan has been
      developed to strengthen nutrition-monitoring efforts in the United States.
      Emphasis is placed on improving coordination and comparability among data
      collection methods across federal agencies and on conducting relevant research.
      Current collaborative efforts between the US Departments of Health and Human
      Services (DHHS) and Agriculture (USDA) include coordinating the national food
      consumption surveys in the areas of planning population coverage, by using
      comparable dietary intake methods, and targeting research toward improving
      dietary methods. The National Health and Nutrition Examination Survey (NHANES)
      contributes population data on diet, nutritional status, and health outcomes to
      the Nutrition Monitoring Program. The third NHANES (1988-1994) includes 40,000
      noninstitutionalized people aged > or = 2 mo and oversamples blacks, Mexican
      Americans, children, and elderly people and uses an automated 24-h recall as the
      primary dietary instrument. Assessing dietary intake in heterogeneous populations
      in national surveys poses many methodologic, statistical, and interpretive issues
      and highlights the need for specific research to improve dietary assessment
      methods.

PMID- 8279417
TI  - Research needs for dietary assessment and monitoring in the United States.
AB  - The 10-y Plan for the National Nutrition Monitoring and Related Research Program
      calls for research related to dietary data collection and interpretation and for
      improved data dissemination. The United States Department of Agriculture Human
      Nutrition Information Service has released data from the 1989 Continuing Survey
      of Food Intakes by Individuals and is planning for the next one. Respondent
      burden will be reduced. The sample is designed for improved estimates of dietary
      intakes for children and elderly individuals. An automated coding system will
      contribute to improved data management. Current research projects include
      developing data collection strategies in a cognitive research laboratory,
      exploring alternative interview structures for children, and developing methods
      to estimate the distributors of usual intakes of nutrients and foods. Priorities
      for further research and development are applying cognitive psychology research
      techniques to improve accuracy of responses, ensuring the temporal validity of
      food-composition databases, and developing the probability approach for assessing
      dietary adequacy.

PMID- 8279418
TI  - Future directions in the development of food-frequency questionnaires.
AB  - The clear documentation during the last decade that dietary intake can be
      measured by standardized food-frequency questionnaires has been fundamentally
      important for understanding the relation between dietary composition and health.
      Energy-adjusted correlation coefficients comparing nutrients assessed in this
      manner with those measured by dietary records or recalls have generally been in
      the range of 0.4-0.7 for a wide variety of populations and with use of
      questionnaires that have varied greatly in length and detail. The latter finding,
      however, suggests that major increments in validity are not likely to be obtained
      by further refinements, although even modest gains are worthy of continued
      efforts. Additional effort must be given to developing and evaluating
      questionnaires that extend the range of ages, populations, settings, and dietary
      factors that are studied. Comparisons with biochemical indicators of intake
      should be used when possible. Even well-established methods of assessment must be
      continually modified because of the rapidly changing patterns of food consumption
      and dietary composition within contemporary populations.

PMID- 8279419
TI  - Gaps in dietary assessment methodology: meal- vs list-based methods.
AB  - The development of new methods and approaches to dietary assessment has not kept
      pace with advances in related disciplines. One of the main gaps is the lack of
      innovation in incorporating cognitive psychology and computer game technology in
      developing useful, less biased tools for epidemiologic research on diet and
      disease. Another problem is the general lack of validation studies imbedded
      within research projects to provide data for assessment and correction of
      measurement error. Conceptual clarity, not only about the dietary components of
      interest but also about the relevant time frame for the disease under study, is
      often deficient in the designs of nutritional epidemiologic studies. Inadequate
      training of nutritional epidemiologists regarding the information requirements of
      a given study is also a problem, resulting either in "overkill," ie, the
      collection of unnecessarily detailed information at great cost, or in powerless
      studies, where the information is inadequate for testing the hypothesis of
      interest.

PMID- 8279420
TI  - Gaps in epidemiologic research methods: design considerations for studies that
      use food-frequency questionnaires.
AB  - It is increasingly common for analytic epidemiology studies of diet and disease
      to select a semi-quantitative food-frequency questionnaire for dietary
      assessment. Reasons include its low cost and focus on usual intake. However, the
      components of variation in nutrient intake based on such methods are poorly
      understood, and it does not provide a quantitative estimate of nutrient intakes.
      Because it is unlikely that such methods will be improved substantially, studies
      using a food-frequency questionnaire should include a dietary standardization
      substudy. A substudy, conducted in a sample of study participants and aimed at
      collecting multiple days of diet recall or record, provides data for quantitative
      calibration of frequency-derived nutrient intake estimates and adjustment of risk
      estimates for measurement error. Attention should also be directed at other
      aspects of study design, such as study population selection to maximize dietary
      exposure contrasts, that can increase the informativeness of epidemiologic
      studies.

PMID- 8279421
TI  - Assessing change in diet-intervention research.
AB  - In nutrition-intervention research, it is important to consider the sensitivity
      of dietary assessment instruments to the changes in nutrient intake or dietary
      behavior under study. This presentation describes a measure called
      "responsiveness," an index of an instrument's sensitivity to change.
      Illustrations of this measure are from two randomized dietary-intervention trials
      that targeted reductions in fat intake: the Women's Health Trial (WHT), a trial
      to test whether fat reduction would reduce the risk of breast cancer, and the
      Eating Patterns Study (EPS), a trial to evaluate a self-help booklet to promote
      dietary change. In the WHT, a 4-d diet record (FDDR) was only slightly more
      responsive to dietary change than was a food-frequency questionnaire (FFQ). In
      the EPS, a fat-related diet-habits questionnaire was most responsive, followed by
      an FDDR and an FFQ. These data suggest that short, inexpensive measures such as
      FFQs or questionnaires that assess dietary habits can be as responsive as
      multiple-day diet records. More research is needed on the relative responsiveness
      of dietary assessment tools. Intervention studies should include at least two
      types of dietary assessment tools and the relative validity, reliability, and
      responsiveness of these tools should be reported as part of the study outcome.

PMID- 8279422
TI  - Walk a mile in my shoes: culturally sensitive food-habit research.
AB  - Issues of cultural meaning loom large in efforts to gather dietary data accurate
      enough to support nutritional analyses, identify marginal diets, or relate risk
      to dietary pattern. When scientifically trained researchers work in nonscientific
      settings--which are common in both the Western and non-Western worlds--many
      important problems of design, collection, and interpretation arise. Assumptions
      about the appropriateness of dietary patterns vary markedly from setting to
      setting, including assumptions about who makes dietary decisions. The definition
      of risk that is meaningful to food specialists may not be so to target
      populations. Even attitudes toward asking questions vary from society to society.
      Researchers can resolve many cultural communication issues by awareness,
      attention, and judicious combination of culturally sensitive qualitative and
      quantitative research techniques.

PMID- 8279423
TI  - Development and validation of dietary assessment methods for culturally diverse
      populations.
AB  - Culturally diverse populations with variable dietary and disease patterns provide
      a unique opportunity for conducting epidemiologic studies to identify the role of
      diet in the etiology of chronic diseases. The dietary method for epidemiologic
      studies, such as cohort or case-control studies, should generally be a diet
      history (or quantitative food frequency) of selected food items consumed during a
      usual month. Knowledge of the eating patterns of each ethnic group in the study
      is needed to develop an appropriate questionnaire. The diet history may be
      validated by collecting multiple 24-h recalls or food records from representative
      samples of each ethnic group and comparing the mean dietary intakes with the
      values obtained from the diet history. Examples of studies of culturally diverse
      populations and the development and validation of the dietary methods are
      discussed.

PMID- 8279424
TI  - Validation of a food-repertory grid with a diabetic population.
AB  - The application of a psychology tool, the repertory grid, was explored. A
      diabetic sample was used to evaluate this new assessment tool. The grid measures
      attitudes about food and was created by determining elements (food items) and
      constructs (adjectival phrases) as identified by diabetic participants and
      dietitians. The grid was administered twice to 17 diabetic participants to
      determine applicability. The interindividual correlation coefficients ranged from
      0.24 to 0.54 for elements and from 0.24 to 0.61 for constructs. The most stable
      components can be used for a grid designed to help dietitians with counseling.
      Clients would fill out a grid so that problem areas in the way of attitudes about
      food could be pinpointed. Because many diabetic persons fail to comply with their
      diets, a new and innovative tool is needed. The possibilities for grid
      development are abundant among other clinical populations for whom dietary
      management is important.

PMID- 8279425
TI  - Use of a multicultural food-frequency questionnaire with pregnant and lactating
      women.
AB  - In a multicultural society the difficulty experienced by pregnancy care teams in
      asking subjects to remember what they have eaten and then adjusting the food
      recall for lapses in detail related to portion size, product names, food
      combinations, and ethnic uniqueness poses a handicap for collecting food-recall
      data. The purpose of this study was to design and administer a food-frequency
      questionnaire (FFQ) to clarify the 24-h dietary recall of pregnant and lactating
      women of Caribbean and African descendants. Focus groups convened in eight states
      around the United States determined ethnic food nomenclature, methods of
      preparation and cooking, types of and additions to food, and cultural differences
      in quantifying food servings. The FFQ assessed weekly intake patterns of six
      categories of foods and described the frequency of consumption of 82 food items.
      Correlation analysis and paired t tests compared agreement indicators (0.80) and
      differences on the reporting.

PMID- 8279426
TI  - Environmental influences on methods used to collect dietary data from children.
AB  - When collecting dietary data on children, confidence about responses is required.
      Children exist in multienvironments in their everyday lives, eg, the personal,
      school, home, peer, medical care, media, food industry, and fast-food facility
      environments. These macroenvironments influence the format and type of data
      collection methods used to interview today's youth. Researchers should identify
      the influence of each environment on the child's eating pattern and nutrient
      intake, explore the pros and cons of various data-collection methods amid these
      environments, and determine unresolved methodological issues to stimulate future
      research. Standardized protocols for interviewing children, exclusion criteria
      for surrogate responses, and currency of nutrient data for new food products
      available to children are needed. Redefining our methods by understanding the
      macroenvironments of youth can create a dietary methodology for the 21st century-
      an evolutionary method that builds on past research and incorporates current
      technology and societal changes.

PMID- 8279427
TI  - A cognitive model of children's reporting of food intake.
AB  - A model of cognitive processing is proposed to understand children's self-reports
      of diet. The model is a simplification of what is known about cognitive
      processing and includes three structural components: sensory register, short-term
      memory, and long-term memory. Several processes describe functioning of the
      model, including attention, perception (or interpretation), organization,
      retention, retrieval, and response formulation. The ideas explain several
      phenomena in the literature on children's self-reports of dietary intake.
      Research questions are identified for each process to help specify the model and
      lead to improved methods for dietary assessment in children.

PMID- 8279428
TI  - Accuracy of fourth- and fifth-grade students' food records compared with school
      lunch observations.
AB  - Fourth- and fifth-grade students' food records completed by using a labor
      intensive approach (with daily monitoring) or a less labor-intensive approach
      (with weekly monitoring) were compared with school-lunch observations. Records
      were completed at three elementary schools for 14-23 d by students in 26 classes.
      Record pages were printed forms with areas for recording items consumed, number
      of servings, and locations of meals. Students were randomly selected for lunch
      observation. Kappa coefficients and percent of agreement for interobserver
      reliability for both approaches combined ranged from 0.43 to 0.91 and 72.6% to
      95.5%, respectively, on 24 observations. Pearson correlations for 117
      record/observation matches were significant for eight and three of nine meal
      items for the daily and weekly monitoring approaches, respectively. Thus,
      students were reasonably accurate in keeping records and more accurate with the
      more labor-intensive approach. Researchers need to select an approach based on
      the degree of accuracy desired and available finances.

PMID- 8279429
TI  - Assessing diets of elderly people: problems and approaches.
AB  - This paper deals with the question of whether dietary assessment methods
      developed and validated for younger adults can be used in surveys for elderly
      people. From the literature it is clear that a decline in short-term memory with
      age makes the 24-h recall method particularly unreliable. Better results have
      been obtained with other methods, especially when a combination of methods is
      used and equipment is adapted for use by older people. However, validity of these
      methods when applied in older people is dependent on the group of elderly people
      under study and the type of information required for the purpose of the study. As
      an example, the validity of the adapted dietary-history method used in the Survey
      in Europe on Nutrition and the Elderly a Concerted Action (SENECA) is discussed.
      This method showed good agreement with the weighed record and with other
      evaluation criteria.

PMID- 8279430
TI  - The NHANES III Supplemental Nutrition Survey of older Americans.
AB  - The number of Americans aged > or = 65 y will reach 70 million by the mid-21st
      century. Health and nutritional-status data for older populations are urgently
      needed to identify future health resource and program needs. The Third National
      Health and Nutrition Examination Survey (NHANES III), a 6-y survey of the
      civilian, noninstitutionalized US population > or = 2 mo old began in 1988;
      approximately 7000 of the 30,000 examinees are aged > or = 50 y. The NHANES III
      dietary assessment component includes 24-h dietary recall and food-frequency
      interviews; information on dietary practices, vitamin and mineral supplement use,
      food sufficiency, and functional status is obtained. The National Institute on
      Aging funded a special dietary study to collect two independent replicate 24-h
      recalls by telephone from NHANES III-Cycle I examinees aged > or = 50 y. The
      expanded dietary data set for older people will be analyzed to examine
      characteristics of in-house and telephone dietary interviews and to examine
      factors previously shown to affect energy and nutrient intake estimates for older
      people.

PMID- 8279431
TI  - The use of 24-h urine samples and energy expenditure to validate dietary
      assessments.
AB  - The doubly labeled-water technique can be used as a noninvasive measure of energy
      expenditure, and, with no gains or losses in weight, expenditure should equal
      intake. Provided sufficiently complete urine collections are obtained, urine
      nitrogen is an accurate measure of protein intake in individuals in nitrogen
      balance. Validations of dietary surveys by using estimates of energy expenditure
      and the 24-h urine nitrogen technique show that inaccurate reports of food intake
      occur in a proportion of individuals within a group, leading to bias in overall
      average intakes for some nutrients, if only one method of dietary assessment is
      used. Errors between methods however are not usually correlated, so that improved
      estimates can be obtained from a combination of two or more methods of dietary
      assessment. All future dietary surveys should require independent evidence of
      their validity.

PMID- 8279432
TI  - Collection of dietary-supplement data and implications for analysis.
AB  - The role of nutrient intake in disease outcome is often examined in epidemiologic
      studies. Most such studies conducted in the United States, however, have not
      included fortified foods or vitamin supplements. In the United States, these are
      important sources of vitamins C and E, but not of beta-carotene. In addition, the
      importance of these nutrient sources varies by race, sex, and age. Failure to
      include these sources produces errors in nutrient estimates, notable
      misclassification of individuals with regard to their total intake, and rankings
      of intake that bear little or no relationship to blood concentrations of those
      nutrients. Implications for statistical analysis are also considered. Risk
      analyses in which nutrients from supplements are handled as control variables or
      are analyzed separately may impair the ability to detect associations between
      total nutrient intake and disease risk. The additional source of
      misclassification of nutrient status for vitamins C and E and other nutrients
      derived from fortified foods or supplements would make it more difficult to
      obtain significant and consistent results in etiologic studies of these
      nutrients; this has not been a factor for beta-carotene, which is derived almost
      exclusively from fruits and vegetables.

PMID- 8279433
TI  - Use of food-intake surveys to estimate exposures to nonnutrients.
AB  - Several steps must be taken in estimating intake of (or exposure to) dietary
      nonnutrients such as additives, drug residues, pesticide residues, toxicants, and
      natural nontoxicant chemicals. The first step involves consideration of relevant
      characteristics of the nonnutrient, including biological activity,
      physical/geographical sources, distribution in the food supply, typical
      concentrations, and the desirability of intake. After reviewing chemical
      characteristics, appropriate food-consumption data to use in the exposure
      assessment must be identified and obtained. Survey methodology must be reviewed
      carefully to determine compatibility with the characteristics of the chemical.
      The best available nonnutrient concentration data must be identified and obtained
      and the exposure models must be chosen. Available models include average
      exposure, simple distribution, joint distribution, and commodity contribution.

PMID- 8279434
TI  - Adjustment for bias due to errors in exposure assessments in multicenter cohort
      studies on diet and cancer: a calibration approach.
AB  - An advantage of multicenter cohort studies on diet and cancer is that these may
      include populations over a wide range of dietary exposure. With some simplifying
      assumptions, the information from such multicenter studies may be divided into 1)
      estimated relationships within each of the separate cohorts, between individual
      level measurements of dietary exposure and disease outcome, and 2) an estimated
      between-cohort relationship, between the mean intake measurements and mean
      incidence rates. Errors in the dietary exposure measurements may lead to
      different amounts of bias in each of these estimated relationships, in particular
      when dietary questionnaire methods cannot easily be standardized. A calibration
      approach can be used to adjust for such differences in bias. This will improve
      the relative weighting of within- and between-cohort components of evidence for a
      diet-disease association.

PMID- 8279435
TI  - Methodologic issues for pooling dietary data.
AB  - This paper presents the methodologic issues to consider when conducting a pooled
      analysis of data from nutritional epidemiologic studies. Because a wide variety
      of dietary assessment methods have been used in nutritional epidemiology, pooled
      analyses often combine data collected under very different circumstances. Whether
      these different methods influence the results obtained in a pooled analysis has
      not yet been examined. One of the main concerns in a pooled analysis is whether
      the data to be pooled are comparable. Questions to consider regarding data
      comparability and methods to address these questions in a pooled analysis are
      discussed.

PMID- 8279436
TI  - Approaches to analysis of dietary data: relationship between planned analyses and
      choice of methodology.
AB  - Dietary intake cannot be estimated without error and probably never will be. The
      nature and magnitude of the error depends on both the dietary data collection
      methodology and the subjects studied. The impact of particular types of error
      depends on the question being asked and the analytical methodology used to
      address it. Examples of these phenomena are presented in this review paper. The
      future lies in improved estimation and understanding of the error terms and in
      the development of analytical and statistical methods of coping with these error
      terms rather than with "improvements" in dietary methodology per se.

PMID- 8279437
TI  - Statistical issues related to semiquantitative food-frequency questionnaires.
AB  - Semiquantitative food-frequency (SQFF) questionnaires have been used by many
      epidemiological studies to collect dietary data. These methods are especially
      attractive for use in large-scale studies because they are often self
      administered and/or completed with minimal time or effort. This paper discusses
      several statistical issues related to the use of dietary data collected by
      frequency methods. In particular, the paper addresses 1) whether SQFF methods are
      well-validated dietary methods as suggested by many investigators and 2) whether
      data based on SQFF methods can be used to compare mean dietary intakes among
      different populations and to estimate the distribution of usual nutrient intakes
      in a national probability population. Data from several validation studies are
      used to evaluate the impact on statistical analyses of measurement error
      associated with certain SQFF methods. These examples help to illustrate the
      potential problems and clarify the interpretation of the results. In addition,
      concerns about the misuse of dietary data derived from SQFF questionnaires are
      also discussed.

PMID- 8279438
TI  - Use of the multiple-day weighed record for Senegalese children during the weaning
      period: a case of the "instrument effect".
AB  - In West Africa, the multiple-day weighed record is the most widely used technique
      for measuring children's food intakes. The children's eating behavior might be
      disrupted by the frequent weighings and the presence of a field-worker in the
      home. We explored the possibility of such an "instrument effect" in a 7-d food
      survey of 70 Senegalese children aged 10-13 mo. Energy intakes decreased
      significantly during the food survey (P < 0.0001). The decrease affected both
      daytime breast milk intake (8%) and solid food intakes (15%). The children's
      weight gain also decreased from a presurvey value of 6.9 to 2.1 g.kg-1.wk-1,
      indicating that their intakes during the food survey were lower than their usual
      intakes. The food-survey methodology was responsible for this "instrument
      effect." Policy decision-makers should be aware that data collected with the
      multiple-day weighed record technique might not reflect African children's usual
      food intakes.

PMID- 8279439
TI  - Dietary assessment issues of concern to policymakers: statement from the Food and
      Agriculture Organization of the United Nations.
AB  - Since its establishment in 1945, the Food and Agriculture Organization of the
      United Nations (FAO) has worked with member countries to increase food production
      and food supplies and improve the nutritional well-being of the world population.
      Dietary assessment is an important component in the process of identifying groups
      that are nutritionally at risk and in developing appropriate programs and
      policies to improve nutritional well-being. However, simpler, more cost-effective
      methods are needed that will allow rapid analysis of survey results so that
      information can be readily available to policymakers at all levels. FAO continues
      to work toward development of methods to improve nutrition monitoring and
      surveillance for developed and developing countries.

PMID- 8279440
TI  - Dietary assessment issues of concern to policymakers: statement from the World
      Health Organization.
AB  - The uses of dietary assessment are many and are increasing as are the demands for
      better quality of the dietary data collected. International meetings on dietary
      assessment methodology provide opportunities for sharing experiences and for in
      depth discussion among those from different countries who are working to solve
      similar problems. Although the state of assessment methodology has improved,
      continued efforts are needed worldwide to further enhance expertise in dietary
      assessment at local levels. Strategies to improve dietary assessment include
      increasing awareness among policymakers and academics of the existence of high
      quality information about what people eat and how this information may or may not
      be used, improving communication and dissemination of available nutrition
      information, and continuing to improve the quality of the information collected
      and the speed with which it is put to use.

PMID- 8279441
TI  - The need for improved methods of diet assessment for developing and monitoring
      food policy in Eastern Europe.
AB  - There is increasing evidence that diseases of major public health importance are
      causally related to nutritional imbalance. Development of nutrition policy to
      improve the nutritional status of a population requires reliable information
      about food consumption and its impact on the health of the population. Available
      methods are useful but not accurate enough. Assessment of the nutritional status
      of representative samples of the general population requires improved methods of
      dietary intake assessment. A combination of different methods provides more
      reliable information than the use of a single method. For example, comparison of
      food balance sheets and households budget surveys provides more useful
      information than either method alone. An international effort should be
      undertaken to identify reliable methods of dietary assessment suitable for all
      countries. Because the development of new methods would be time consuming,
      efforts should be focused on the selection of existing methods, their
      improvement, standardization, and implementation. International organizations
      such as the Food and Agriculture Organization and the World Health Organization
      should give high priority to the improvement of methods useful in nutritional
      epidemiological studies.

PMID- 8279442
TI  - Research priorities and recommendations for dietary assessment methodology. First
      International Conference on Dietary Assessment Methods.
AB  - A list of research priorities related to dietary assessment methodology is
      presented. The priorities are based on a consensus of opinion by a
      multidisciplinary international group of experts who participated in the First
      International Conference on Dietary Assessment Methods. These experts included
      researchers in dietary assessment methodology, major users of dietary assessment
      methods, and policymakers involved in setting food and nutrition policies. The
      list of priorities may be used as a guide for planning future research in dietary
      assessment methods, for prioritizing the allocation of available research
      resources, and for planning subsequent conferences. A list of recommendations
      related to dietary assessment methodology is also presented. Procedures used by
      the conference planners to select the experts are described, and the need for
      developing objective criteria for ranking priorities is discussed. An ongoing
      function of the conference series will be to continue the process of revising the
      priorities and recommendations to reflect progress made and newly identified
      needs in dietary assessment methodology.

PMID- 8279443
TI  - Cervicovaginal smear, true or false?

PMID- 8279444
TI  - The relative usefulness of automated apolipoprotein A-I and high-density
      lipoprotein cholesterol assays as markers for coronary artery disease.
AB  - Research studies have shown that apolipoprotein A-I (apo A-I) is a better marker
      for coronary artery disease (CAD) than high-density lipoprotein cholesterol
      (HDLC). Yet, it is unclear whether assays for apolipoprotein A-I, which is part
      of macromolecular lipoprotein complex, can perform as well when measured by
      routine automated clinical laboratory techniques. The purpose of this study was
      to compare automated apolipoprotein A-I assays with HDLC as a marker for CAD. The
      authors studied two groups of angiographically documented men, aged 44-70 years,
      42 with CAD and 123 without CAD in an unmatched, controlled study. Standard
      clinical laboratory techniques for assaying HDLC, and automated kit rate
      immunonephelometric, end point immunonephelometric, and immunoturbidimetric
      assays for apolipoprotein A-I were used. High-density lipoprotein cholesterol was
      a better marker than apolipoprotein A-I, according to the Mann Whitney test; HDLC
      also showed better diagnostic sensitivity, specificity, and predictive value.
      Using a precipitation method, HDL3 was a better marker than HDL2, but not as good
      as total HDLC. The authors concluded that HDLC remains the best routine single
      CAD marker commonly available for evaluation of HDL status in a high-risk
      population.

PMID- 8279445
TI  - Plasma thrombomodulin as a marker of vascular injuries in collagen vascular
      diseases.
AB  - Thrombomodulin, a thrombin receptor on the vascular endothelial cell surface, is
      released into circulating blood. The plasma concentrations in patients with
      collagen vascular diseases, including systemic lupus erythematosus (SLE),
      rheumatoid arthritis, juvenile rheumatoid arthritis, Sjogren's syndrome, systemic
      sclerosis, polymyositis and/or dermatomyositis (PM/DM), Behcet's disease, and
      Wegener's granulomatosis, were measured and compared with those of healthy
      persons. The mean plasma thrombomodulin concentrations in patients with juvenile
      rheumatoid arthritis, systemic sclerosis, PM/DM, Wegener's granulomatosis, and
      active states of SLE, rheumatoid arthritis, and Bechet's disease were
      significantly higher than those in the control group. Patients with Wegener's
      granulomatosis showed the highest mean value. The mean values in patients with
      inactive states of the diseases and Sjogren's syndrome were not significantly
      different from the values in the control group. In cases of juvenile rheumatoid
      arthritis, systemic sclerosis, PM/DM, and Wegener's granulomatosis, patients with
      active interstitial pneumonitis or extensive pulmonary lesions frequently showed
      higher values of plasma thrombomodulin than those without overt pulmonary
      involvement. Elevated plasma thrombomodulin values were decreased along with
      amelioration of the diseases by treatment. These results may indicate that plasma
      thrombomodulin measurement may be helpful for evaluating vascular injury in
      patients with collagen diseases.

PMID- 8279446
TI  - Colony-stimulating factor and macrophage proliferation.

PMID- 8279447
TI  - Colony-stimulating factor and macrophage proliferation.

PMID- 8279448
TI  - Absence of Epstein-Barr virus DNA in lymphoepithelioma-like carcinoma of the the
      uterine cervix.

PMID- 8279449
TI  - Cell abnormalities associated with human papillomavirus-induced squamous
      intraepithelial cervical lesions. Multivariate data analysis.
AB  - One hundred ninety-six cervical scrapings were obtained for simultaneous research
      of cell abnormalities in Papanicolaou smears and detection of genital human
      papillomavirus (HPV) genotypes by polymerase chain reaction in extracted DNA from
      each clinical sample. The samples described by six discriminant cytologic
      parameters, and a synthetic HPV-presence/absence parameter provided an efficient
      matrix for multiple correspondence analysis. This statistical analysis displayed
      a plurality of HPV-related cell abnormalities in squamous intraepithelial
      lesions, and a high correspondence between HPV infection and the presence of
      multinucleated squamous cells, morphologically transformed keratinocytes
      (dyskaryotic cells), koilocytes, and cellular changes related to epithelial
      maturation. Because of the low proportion of detectable koilocytes in the HPV
      infected scrapings, the authors also inferred that cellular changes related to
      epithelial maturation and morphologically transformed keratinocytes are the most
      accurate and efficient cell abnormalities, in terms of frequency and correlation,
      for cytodiagnosis of HPV-induced or associated squamous intraepithelial cervical
      lesions.

PMID- 8279450
TI  - Review of negative Papanicolaou tests. Is the retrospective 5-year review
      necessary?
AB  - New federal regulations require review of all available negative gynecologic
      smears within the previous 5 years for each patient with a current high grade
      squamous intraepithelial lesion (HGSIL) or above. Two university hospitals
      retrospectively reviewed all patients who had HGSIL or above and who had prior
      negative smears. During 18 months, 35,807 Papanicolaou tests were reported, from
      which we identified 44 patients with 80 negative smears before presenting with
      HGSIL or above. These 80 negative smears were rescreened and, on review, there
      was agreement with the original diagnosis in 66 cases (82.5%). Fourteen (17.5%)
      smears were reclassified: 2 unsatisfactory, 6 atypical squamous/glandular cells
      of undetermined significance, 3 low grade SIL, and 3 HGSIL or above. Of the 12
      cases satisfactory for reclassification, 9 (75%) occurred within 2 years before
      the HGSIL or above. Two cases of atypical squamous/glandular cells occurred
      within 4 years. One case of HGSIL occurred more than 4 years before, but a
      negative Pap smear had been reclassified within the year before the diagnosis of
      HGSIL. The authors conclude that a 2-year retrospective review, which identified
      75% of our false-negative cases, is an effective and efficient quality control
      and assurance practice.

PMID- 8279451
TI  - Mineralizing pulmonary elastosis in chronic cardiac failure. "Endogenous
      pneumoconiosis" revisited.
AB  - The histopathology, ultrastructure, and clinicopathologic correlations in six
      patients with cardiac failure and iron encrustation of lung elastic tissue were
      examined at autopsy. Transmission electron microscopy (TEM) and energy dispersive
      x-ray analysis were applied to two cases. Of the group, five patients had cardiac
      failure due to systemic hypertension (4 patients), valvular disease (4 patients),
      or coronary atherosclerosis (4 patients). Biventricular failure in one patient
      was associated with sleep apnea. Both iron and calcium, identified by
      histochemical stains, impregnated degenerated alveolar and vascular elastic
      fibers and were associated with a foreign body reaction and focal interstitial
      fibrosis. Energy dispersive x-ray analysis and TEM demonstrated iron and calcium
      on the microfibrillar portion of elastin. Morphometry indicated vascular changes
      of pulmonary venous hypertension. The authors concluded that mineral deposition
      probably represents nonspecific precipitation of metallic ions on altered elastic
      fibers in patients with cardiac failure. "Mineralizing elastosis" potentially
      contributes to lung restriction and, occasionally, can be a source of diagnostic
      confusion.

PMID- 8279453
TI  - The laboratory's role in diagnosing enterohemorrhagic Escherichia coli
      infections: helping the doctor out.

PMID- 8279452
TI  - Autonomously functioning (hot) nodule of the thyroid gland. A clinical and
      histopathologic study of 17 cases.
AB  - The authors present the clinical and pathologic findings of 17 patients with
      autonomously functioning (hot) nodule of the thyroid (AFNT). The patients were 13
      to 68 years of age, and 12 were female. Five had obvious laboratory findings of
      hyperthyroidism, but the other 12 were euthyroid. Fifteen patients had solitary
      or multiple benign nodules. The remaining two had autonomously functioning
      carcinomas; one of these patients had a papillary carcinoma with no distant
      metastases, and the other had a follicular carcinoma with widespread metastases.
      Total thyroidectomy was performed in one patient, subtotal thyroidectomy was
      performed in four, and hemithyroidectomy in eight. Diagnostic large needle biopsy
      was performed in only four patients. Of the 13 patients undergoing thyroidectomy,
      3 had multiple hot nodules, and 10 had a solitary hot nodule. The size of the
      nodules ranged from very small to 6 cm, with no definite correlation found
      between the size of the nodule and thyroid function. Pathologically, cystic
      change and hemorrhage to various degrees were common features of AFNT. On
      histologic examination of the nodules, 13 were diagnosed as follicular adenoma (6
      predominantly macrofollicular; 4 mixed micro-, normo-, and macrofollicular; and 3
      predominantly papillary) and 2 as adenomatous goiter (1 predominantly papillary
      and 1 predominantly macrofollicular). The remaining two were diagnosed as
      carcinoma (1 follicular variant of papillary carcinoma and 1 follicular
      carcinoma). Two children had benign nodules showing a predominantly papillary
      architecture. Microcarcinoma outside the nodules was found in two patients, and
      both microcarcinomas were a papillary type. The AFNTs showed characteristic
      pathologic findings, and the pathologic differentiation of AFNTs from usually
      observed nonfunctioning (cold) nodules was not difficult. Pathologists should pay
      particular attention to AFNTs showing a papillary architecture, because these
      papillary lesions are sometimes mistaken for papillary thyroid carcinoma.

PMID- 8279454
TI  - Heterogeneity of rearranged T-cell receptor V-alpha and V-beta transcripts in
      tumor-infiltrating lymphocytes from Hodgkin's disease and non-Hodgkin's lymphoma.
AB  - Hodgkin's disease is histologically characterized by the presence of Reed
      Sternberg cells (RSC) and reactive cells, including numerous T lymphocytes. Some
      forms of B cell-non-Hodgkin's lymphoma also contain a rich T-cell population.
      Previous studies have suggested that the T-cell receptor repertoire of tumor
      infiltrating T lymphocytes (TITL) that act specifically against tumor-related
      antigens, should be restricted. The authors in this study used the polymerase
      chain reaction to explore the possible existence of such an immunologic response
      of TITL against RSC or neoplastic B cells. They studied variable (v) region genes
      of T-cell receptor alpha and beta chains expressed by infiltrating lymphocytes in
      biopsy specimens from seven patients with Hodgkin's disease and three with B cell
      non-Hodgkin's lymphoma. These latter samples were selected based on a rich T-cell
      content. Primers specific for 18 different V-alpha and 21 V-beta families were
      used. In every case, TITL showed an unrestricted pattern of expression similar to
      the repertoire observed in peripheral blood lymphocytes. Although such
      experiments are limited, the apparent lack of selection of a single or a limited
      number of T-cell subsets in the affected tissues did not support the existence of
      an in vivo immunologic interaction between TITL and antigens related to RSC or
      neoplastic B cells.

PMID- 8279455
TI  - Marrow cellularity as a predictor of adequate cell yield for transplantation.
AB  - Clear correlations have not been established between bone marrow cellularity
      before or at marrow harvest and marrow cell yield for transplantation. The
      authors therefore retrospectively reviewed 204 marrow donations to ascertain
      whether biopsy cellularity was predictive of nucleated cell yield at harvest, as
      measured by final cell counts (FCC)/kg body weight. Preharvest and intraoperative
      biopsy cellularity were highly correlated with each other; moderate correlation
      was found between intraoperative biopsy cellularity and FCC. Mean cellularity was
      slightly but significantly higher in samples yielding an FCC greater than 2 x
      10(8) nucleated cells/kg (P < 0.01). Biopsy cellularity less than 20%, seen in 4%
      of specimens, did not consistently correlate with low FCC, defined as less than 2
      x 10(8) nucleated cells/kg. More than 2 x 10(8) cells/kg were consistently
      obtained only when biopsy cellularity was 65% or more. Marrow biopsies performed
      before harvest can be used to predict intraoperative cell counts at the time of
      marrow donation, although a cell yield of more than 2 x 10(8) nucleated cells/kg
      can be assured only with high marrow cellularity.

PMID- 8279456
TI  - Evaluation of automated reticulocyte counts and their reliability in the presence
      of Howell-Jolly bodies.
AB  - An automated reticulocyte procedure using a flow cytometer and the fluorescent
      dye thiazole orange was evaluated for clinical use. The mean reticulocyte count
      on 118 hematologically healthy adults was 1.56% (standard deviation [SD] 0.54),
      with virtually no difference in percentage between women and men. The mean
      absolute values were 68.4 x 10(9)/L (SD 24.6) and 75.7 x 10(9)/L (SD 27.2),
      respectively. When compared with the standard microscopic technique, the
      automated method showed excellent correlation (r = 0.98) and greatly improved
      precision (coefficient of variation [CV] 4.1%) over the manual method (CV 22.8%).
      Preanalytic storage of blood samples at 4 degrees C for up to 48 hours did not
      significantly affect results, nor did varying the incubation time of diluted
      samples from 1/2 to 2 hours. In a group of patients with appreciable numbers of
      Howell-Jolly bodies, automated reticulocyte counts were spuriously elevated. The
      difference between the manual and automated counts on these patients approximated
      the percentage of Howell-Jolly bodies observed on their Wright-Giemsa stained
      blood smears.

PMID- 8279457
TI  - Mycobacterium genavense. Autopsy findings in three patients.
AB  - The authors report on the pathologic findings in three cases of disseminated
      infection with Mycobacterium genavense, a recently described nontuberculous
      mycobacterium, in human immunodeficiency virus (HIV)-I-positive patients. The
      mycobacterium was identified by amplification of a 16S rDNA gene fragment and
      subsequent sequence determination. The organs mainly involved were the small
      intestine, spleen, liver, and lymph nodes. In contrast, lungs, myocardium, and
      kidneys were not involved, or only minimally involved, in this generalizing
      disease. Histopathologically, infection with Mycobacterium genavense in HIV
      positive patients was mostly characterized by masses of foamy histiocytes and,
      depending on the immunologic reactivity of the host, by ill-formed granulomas,
      rarely with small foci of necrosis. The pathologic findings and clinical features
      were similar to those presented by patients who had generalized infection with
      Mycobacterium avium-intracellulare complex. To obtain more precise information
      about the specific course of infection with Mycobacterium genavense, scrupulous
      microbiologic investigations, including molecular biologic techniques, are
      necessary in cases with mycobacterial infections.

PMID- 8279458
TI  - Charting the process of change: a primer on survival analysis.
AB  - Survival analysis is a powerful and useful technique for understanding
      qualitative change. This article provides a practical, nontechnical introduction
      to the use of survival analysis for social scientists. Important issues in using
      survival analysis are discussed, including research design, data preparation and
      management, and data analysis. Attendance data from a self-help organization are
      used to illustrate common survival analysis tasks such as describing the overall
      survival and hazard functions, examining covariate effects, and modeling the form
      of the hazard function over time. An appendix that discusses the strengths and
      weaknesses of current survival analysis computer programs is included.

PMID- 8279459
TI  - The 1.5-Mb region spanning the myotonic dystrophy locus shows uniform
      recombination frequency.
AB  - The myotonic dystrophy (DM) mutation has been identified as a heritable unstable
      CTG trinucleotide repeat sequence. The intergenerational amplification of this
      sequence is an example of a new class of dynamic mutations responsible for human
      genetic diseases. To ascertain whether recombination activity influences, or is
      affected by, the presence of this unique sequence, a comprehensive study of the
      physical and genetic mapping data for the 1.5-Mb region of human chromosome
      19q13.3, which contains the DM locus, was conducted. The recombination rate for
      this region was examined by correlating genetic distance to physical distance for
      six selected marker loci. The following markers span the DM region: 19qCEN-p
      alpha 1.4 (D19S37)-APOC2-CKM-pE0.8 (D19S115)-pGB2.6 (DM)-p134c (D19S51)-19qTER.
      Initial linear regression analysis of these two parameters failed to reveal a
      significant linear correlation (coefficient of determination, r2 = .19),
      suggesting nonuniform rates of recombination. However, the presence of a
      recombination hot spot was believed to be unlikely, as the marker-to-marker pairs
      that showed the greatest deviation in recombination frequency were not restricted
      to a specific region of the 1.5 Mb studied and had relatively broad confidence
      intervals, as reflected by low LOD values. A second linear regression analysis
      using only marker intervals with high LOD scores (Zmax > 22) showed linear
      correlation (r2 = .68) for the entire 1.5-Mb region. This analysis indicated a
      relatively uniform recombination frequency in the 1.5-Mb region spanning the DM
      locus. Furthermore, the recombinations observed were neither under- nor
      overrepresented on DM chromosomes. Consequently, recombination activity is
      unlikely to influence, or be affected by, the presence of the DM mutation.

PMID- 8279461
TI  - New genetic technologies: our added responsibilities.

PMID- 8279460
TI  - A third locus for autosomal dominant cerebellar ataxia type I maps to chromosome
      14q24.3-qter: evidence for the existence of a fourth locus.
AB  - The autosomal dominant cerebellar ataxias (ADCA) type I are a group of
      neurological disorders that are clinically and genetically heterogeneous. Two
      genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are
      already localized. We have mapped a third locus to chromosome 14q24.3-qter, by
      linkage analysis in a non-SCA1/non-SCA2 family and have confirmed its existence
      in a second such family. We suggest designating this new locus "SCA3". Combined
      analysis of the two families restricted the SCA3 locus to a 15-cM interval
      between markers D14S67 and D14S81. The gene for Machado-Joseph disease (MJD), a
      clinically different form of ADCA type I, has been recently assigned to
      chromosome 14q24.3-q32. Although the SCA3 locus is within the MJD region, linkage
      analyses cannot yet demonstrate whether they result from mutations of the same
      gene. Linkage to all three loci (SCA1, SCA2, and SCA3) was excluded in another
      family, which indicates the existence of a fourth ADCA type I locus.

PMID- 8279462
TI  - Human genome research and the public interest: progress notes from an American
      science policy experiment.
AB  - This essay reviews the efforts of the U.S. Human Genome Project to anticipate and
      address the ethical, legal, and social implications of new advances in human
      genetics. Since 1990, approximately $10 million has been awarded by the National
      Institutes of Health and the Department of Energy, in support of 65 research,
      education, and public discussion projects. These projects address four major
      areas of need: (1) the need for both client-centered assessments of new genetic
      services and for improved knowledge of the psychosocial and ethnocultural factors
      that shape clients' clinical genetic experiences; (2) the need for clear
      professional policies regarding human-subject research, clinical practice
      standards, and public health goals in human genetics; (3) the need for social
      policy protection against unfair access to and use of personal genetic
      information; and (4) the need for improved public and professional understanding
      and discussion of these issues. The Human Genome Project's goal is to have
      defined, by 1995, policy options and programs capable of addressing these needs.

PMID- 8279463
TI  - The Evolving Genome Project: current and future impact.
AB  - The National Institutes of Health/Department of Energy Human Genome Project has
      been funding directed research for only 5 years, and it is understandably
      difficult to cite important research advances directly attributable to the
      project. However, the project has been constructive in fostering
      multidisciplinary group research and an inspiring and synergistic "just do it"
      attitude in both political and scientific circles, domestically and abroad. This
      collaborative spirit has spawned large-scale genetic and physical mapping
      projects, with the most impressive and useful results to date being the dense
      genetic maps produced by the Genethon, a French organization largely supported by
      the French muscular dystrophy association. With the genetic and physical map
      reagents now becoming available, disease-gene cloning is proceeding at an
      increasingly rapid pace. More important than the predictable acceleration of
      disease-gene mapping are the unpredictable benefits: Will a dense PCR-based
      dinucleotide-repeat genetic map open novel alternative approaches to disease-gene
      isolation? Will it become possible to localize disease genes by simply analyzing
      unrelated, isolated probands rather than the rarer "extended family"? Proband
      based "linkage-disequilibrium cloning" may become possible if adequate density,
      informativeness, and stability of polymorphic loci are obtained. In addition,
      "genome exclusion cloning" will be added to the established positional, candidate
      gene, and functional-disease-gene-cloning experimental approaches. The
      anticipated exponential expansion of human genetic disease information over the
      remainder of the 10-year tenure of the Human Genome Project unveils critical yet
      unresolved issues for medical education and the practice of medicine.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279464
TI  - Bioethics for human geneticists: models for reasoning and methods for teaching.
AB  - The ethical issues raised by the Human Genome Project (HGP) and by human genetics
      in general are not entirely novel. In fact, the ethical issues surrounding
      genetic research and the provision of genetic services fit into the evolution of
      bioethics, a field of inquiry which has its roots in concerns of the 1970s,
      concerns about the dignity and self-determination of individuals and about the
      development of medical technologies. Although bioethics has been largely occupied
      with patient-centered concerns, attention is currently shifting toward socially
      oriented issues, such as the justice of the existing health-care system. Genetic
      counseling has already incorporated many of the lessons of early bioethics and,
      as a profession, adheres to a consultand-centered ethic which reflects the values
      incorporated into the doctrine of informed consent, which is a cornerstone of
      bioethics. The mandate of the Ethical, Legal, and Social Implications Program of
      the HGP--to anticipate ethical problems arising from advances in genetics and to
      educate the public about genetics--reflects not only the nonpaternalistic
      approach of early bioethics but also bioethics' increasing attention to the
      ethical import of systemic and institutional factors, as well as an anticipatory
      and preventive approach to dealing with ethical concerns. Because bioethics has
      so much to contribute to current consideration of ethical issues in human
      genetics, it is important to provide training in ethics to those working in the
      field. Guidelines for using a case-oriented approach are suggested.

PMID- 8279466
TI  - Maternal uniparental disomy 22 has no impact on the phenotype.
AB  - A 25-year-old normal healthy male was karyotyped because five of his wife's
      pregnancies terminated in spontaneous abortions at 6-14 wk of gestation.
      Cytogenetic investigation disclosed a de novo balanced Robertsonian t(22q;22q)
      translocation. Molecular studies revealed maternal only inheritance for
      chromosome 22 markers. Reduction to homozygosity for all informative markers
      indicates that the rearranged chromosome is an isochromosome derived from one of
      the maternal chromosomes 22. Except for the possibility of homozygosity for
      recessive mutations, maternal uniparental disomy 22 does not seem to have an
      adverse impact on the phenotype, apart from causing reproductive failure. It can
      be concluded that no maternally imprinted genes with major effect map to
      chromosome 22.

PMID- 8279465
TI  - The Human Genome Project and eugenic concerns.
AB  - The U.S. Human Genome project is the largest scientific project funded by the
      federal government since the Apollo Moon Project. The overall effect from this
      project should be of great benefit to humankind because it will provide a better
      understanding both of single gene defects and multifactorial or familial diseases
      such as diabetes, arteriosclerosis, and cancer. At first this will lead to more
      exact ways of screening and diagnosing genetic disease, and later it will lead,
      in many if not most instances, to specific genetic cures. However, in the past,
      in both the U.S. and German eugenic movements genetic information has been
      misused. Hopefully, by remembering and understanding the past injustices and
      inhumanity of negative eugenics, further misuse of scientific information can be
      avoided.

PMID- 8279467
TI  - Genetic linkage mapping of multiple epiphyseal dysplasia to the pericentromeric
      region of chromosome 19.
AB  - Multiple epiphyseal dysplasia (MED) is an inherited chondrodystrophy that results
      in deformity of articular surfaces and in subsequent degenerative joint disease.
      The disease is inherited as an autosomal dominant trait with high penetrance. An
      MED mutation has been mapped by genetic linkage analysis of DNA polymorphisms in
      a single large pedigree. Close linkage of MED to 130 tested chromosomal markers
      was ruled out by discordant inheritance patterns. However, strong evidence for
      linkage of MED to markers in the pericentromeric region of chromosome 19 was
      obtained. The most closely linked marker was D19S215, with a maximum LOD score of
      6.37 at theta = .05. Multipoint linkage analysis indicated that MED is located
      between D19S212 and D19S215, a map interval of 1.7 cM. Discovery of the map
      location of MED in this family will facilitate identification of the mutant gene.
      The closely linked DNA polymorphisms will also provide the means to determine
      whether other inherited chondrodystrophies have underlying defects in the same
      gene.

PMID- 8279468
TI  - Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme
      deficiency with detectable enzyme protein: identification by means of
      complementation analysis.
AB  - We describe four infants with a novel subtype of an isolated deficiency of one of
      the peroxisomal beta-oxidation enzymes with detectable enzyme protein. The
      patients showed characteristic clinical and biochemical abnormalities, including
      hypotonia, psychomotor retardation, hepatomegaly, typical facial appearance,
      accumulation of very-long-chain fatty acids, and decreased lignoceric acid
      oxidation. However, beta-oxidation enzyme proteins were detected by immunoblot
      analyses, and large peroxisomes were identified by immunofluorescence staining.
      In order to identify the underlying defect in these patients, complementation
      analysis was introduced using fibroblasts from these patients and patients with
      an established deficiency of either acyl-CoA oxidase or bifunctional enzyme, as
      identified by immunoblotting. In the complementing combinations, fused cells
      showed increased lignoceric acid oxidation, resistance against 1-pyrene
      dodecanoic acid/UV selection, and normalization of the size and the distribution
      of peroxisomes. The results indicate that two patients with a more severe
      clinical course were suffering from bifunctional enzyme deficiency and that the
      other two infants, who were siblings and had a less severe clinical presentation,
      were the first patients with acyl-CoA oxidase deficiency with detectable enzyme
      protein.

PMID- 8279469
TI  - Three new mutations in patients with myophosphorylase deficiency (McArdle
      disease).
AB  - We report three new mutations in patients with myophosphorylase deficiency
      (McArdle disease). A splice-junction mutation (G-to-A transition at the 5' end of
      intron 14) and a missense mutation (CTG to CCG at codon 291, changing an encoded
      leucine to a proline) were identified in Caucasian patients who were heterozygous
      for a common mutation reported elsewhere (CGA [Arg] to TGA [stop]) at codon 49.
      The splice-junction mutation destroyed the consensus sequence at the 5' splice
      site, and a cryptic splice site 67 bp upstream was recognized instead. As a
      result, there was a 67-bp deletion in the 3'-terminal region of exon 14 in the
      transcript, resulting in a frameshift with premature translation termination. A
      deletion of a single codon, 708/709 (TTC, specifying phenylalanine) was
      identified in Japanese patients. Two affected siblings were homozygotes, and
      their parents were heterozygotes. A third, unrelated patient was heterozygous for
      the same mutation, while the myophosphorylase gene on the other allele was only
      faintly expressed.

PMID- 8279470
TI  - A novel point mutation (G-1 to T) in a 5' splice donor site of intron 13 of the
      dystrophin gene results in exon skipping and is responsible for Becker muscular
      dystrophy.
AB  - The mutations in one-third of Duchenne and Becker muscular dystrophy patients
      remain unknown, as they do not involve gross rearrangements of the dystrophin
      gene. We now report a defect in the splicing of precursor mRNA (pre-mRNA),
      resulting from a maternally inherited mutation of the dystrophin gene in a
      patient with Becker muscular dystrophy. This defect results from a G-to-T
      transversion at the terminal nucleotide of exon 13, within the 5' splice site of
      intron 13, and causes complete skipping of exon 13 during processing of
      dystrophin pre-mRNA. The predicted polypeptide encoded by the aberrant mRNA is a
      truncated dystrophin lacking 40 amino acids from the amino-proximal end of the
      rod domain. This is the first report of an intraexon point mutation that
      completely inactivates a 5' splice donor site in dystrophin pre-mRNA. Analysis of
      the genomic context of the G-1-to-T mutation at the 5' splice site supports the
      exon-definition model of pre-mRNA splicing and contributes to the understanding
      of splice-site selection.

PMID- 8279471
TI  - Mapping of a gene for autosomal dominant juvenile-onset open-angle glaucoma to
      chromosome Iq.
AB  - A large Caucasian family is presented, in which a juvenile-onset form of open
      angle glaucoma is transmitted in an autosomal dominant fashion. Sixteen affected
      family members were identified from 31 at-risk individuals descended from the
      affected founder. Affected patients developed high intraocular pressures
      (sometimes > 40 mm Hg) within the first 2 decades of life. Linkage analysis
      between the disease phenotype and 12 microsatellite repeat markers located on
      chromosome 1q gave a maximum lod score of 8.38 at a recombination fraction of
      zero for marker D1S210. Analysis of recombinant haplotypes suggests a total
      inclusion region of about 14 cM between markers D1S194 and D1S218 at 1q21-q31.
      This represents the second juvenile-glaucoma family, in which the disease has
      been mapped to the long arm of chromosome 1.

PMID- 8279472
TI  - Haplotype studies in Wilson disease.
AB  - In 51 families with Wilson disease, we have studied DNA haplotypes of
      dinucleotide repeat polymorphisms (CA repeats) in the 13q14.3 region, to examine
      these markers for association with the Wilson disease gene (WND). In addition to
      a marker (D13S133) described elsewhere, we have developed three new highly
      polymorphic markers (D13S314, D13S315, and D13S316) close to the WND locus. We
      have examined the distribution of marker alleles at the loci studied and have
      found that D13S314, D13S133, and D13S316 each show nonrandom distribution on
      chromosomes carrying the WND mutation. We have studied haplotypes of these three
      markers and have found that there are highly significant differences between WND
      and normal haplotypes in northern European families. These findings have
      important implications for mutation detection and molecular diagnosis in families
      with Wilson disease.

PMID- 8279474
TI  - Linkage disequilibrium between the juvenile neuronal ceroid lipofuscinosis gene
      and marker loci on chromosome 16p 12.1.
AB  - The neuronal ceroid lipofuscinoses (NCL; Batten disease) are a collection of
      autosomal recessive disorders characterized by the accumulation of
      autofluorescent lipopigments in the neurons and other cell types. Clinically,
      these disorders are characterized by progressive encephalopathy, loss of vision,
      and seizures. CLN3, the gene responsible for juvenile NCL, has been mapped to a
      15-cM region flanked by the marker loci D16S148 and D16S150 on human chromosome
      16. CLN2, the gene causing the late-infantile form of NCL (LNCL), is not yet
      mapped. We have used highly informative dinucleotide repeat markers mapping
      between D16S148 and D16S150 to refine the localization of CLN3 and to test for
      linkage to CLN2. We find significant linkage disequilibrium between CLN3 and the
      dinucleotide repeat marker loci D16S288 (chi 2(7) = 46.5, P < .005), D16S298 (chi
      2(6) = 36.6, P < .005), and D16S299 (chi 2(7) = 73.8, P < .005), and also a novel
      RFLP marker at the D16S272 locus (chi 2(1) = 5.7, P = .02). These markers all map
      to 16p12.1. The D16S298/D16S299 haplotype "5/4" is highly overrepresented,
      accounting for 54% of CLN3 chromosomes as compared with 8% of control chromosomes
      (chi 2 = 117, df = 1, P < .001). Examination of the haplotypes suggests that the
      CLN3 locus can be narrowed to the region immediately surrounding these markers in
      16p12.1. Analysis of D16S299 in our LNCL pedigrees supports our previous finding
      that CLN3 and CLN2 are different genetic loci. This study also indicates that
      dinucleotide repeat markers play a valuable role in disequilibrium studies.

PMID- 8279473
TI  - Refining the position of Wilson disease by linkage disequilibrium with
      polymorphic microsatellites.
AB  - Wilson disease (WND) is an autosomal recessive disorder that is due to an
      inability of the liver to eliminate copper. Copper buildup in the liver, brain,
      kidney, and other tissues can result in liver cirrhosis, neurologic and
      psychiatric defects, and other problems. We have localized the disease-containing
      region to between D13S31 and D13S59, with > 70 multiply affected families, and
      have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine
      highly polymorphic microsatellites. Here we present an analysis of disequilibrium
      with markers in this interval and provide evidence for strong allelic
      associations between AFM084xc5 alleles and WND alleles in European, Middle
      Eastern, and East Asian populations. Significant but weaker allelic associations
      were also observed between WND alleles and alleles at D13S137 and D13S169. The
      strength of the association between AFM084xc5 and WND in all non-Sardinian
      populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests
      that the number of mutations accounting for WND is less than expected on the
      basis of the variety of clinical symptoms that are observed.

PMID- 8279475
TI  - Refining the locus for Best vitelliform macular dystrophy and mutation analysis
      of the candidate gene ROM1.
AB  - Vitelliform macular dystrophy (Best disease) is an autosomal dominant macular
      dystrophy which shares important clinical features with age-related macular
      degeneration, the most common cause of legal blindness in the elderly.
      Unfortunately, our understanding and treatment for this common age-related
      disorder is limited. Discovery of the gene which causes Best disease has the
      potential to increase our understanding of the pathogenesis of all types of
      macular degeneration, including the common age-related form. Best disease has
      recently been mapped to chromosome 11q13. The photoreceptor-specific protein ROM1
      has also been recently mapped to this location, and the ROM1 gene is a candidate
      gene for Best disease. Using highly polymorphic markers, we have narrowed the
      genetic region which contains the Best disease gene to the 10-cM region between
      markers D11S871 and PYGM. Marker D11S956 demonstrated no recombinants with Best
      disease in three large families and resulted in a lod score of 18.2. In addition,
      a polymorphism within the ROM1 gene also demonstrated no recombinants and
      resulted in a lod score of 10.0 in these same three families. We used a
      combination of SSCP analysis, denaturing gradient gel electrophoresis, and DNA
      sequencing to screen the entire coding region of the ROM1 gene in 11 different
      unrelated patients affected with Best disease. No nucleotide changes were found
      in the coding sequence of any affected patient, indicating that mutations within
      the coding sequence are unlikely to cause Best disease.

PMID- 8279476
TI  - PHAVER syndrome: an autosomal recessive syndrome of limb pterygia, congenital
      heart anomalies, vertebral defects, ear anomalies, and radial defects.
AB  - We have studied 2 sibs with vertebral, radial, congenital heart, and ear defects.
      The second patient also had limb pterygia and meningomyelocele. The abnormalities
      in these two sibs are seen in the VATER association; however, distinguishing
      these cases from the VATER association are the findings of pterygia,
      meningomyelocele, and probable autosomal recessive inheritance. We propose the
      acronym PHAVER syndrome for limb pterygia, heart defects, autosomal recessive
      inheritance, vertebral defects, ear anomalies and radial defects. This represents
      a new autosomal recessive disorder with phenotypic variability.

PMID- 8279477
TI  - Three cases of dup(10p)/del(10q) syndrome resulting from maternal pericentric
      inversion.
AB  - Two families and 3 patients with dup(10p)/del(10q) syndrome segregating from a
      maternal pericentric inversion are described, including a stillborn female with
      Potter sequence and multicystic renal dysplasia. Comparison of 32 dup(10p)
      patients to 11 del(10)(q25) patients emphasized dolichocephaly, wide sutures,
      frontal bossing, micrognathia, and renal defects as distinguishing
      characteristics of the dup(10p) syndrome. The 3 new and 6 previously reported
      dup(10p)/del(10q) patients had several manifestations in common with the dup(10p)
      and del(10q) syndromes, but were more typical of dup(10p) syndrome with respect
      to all 5 distinguishing characters.

PMID- 8279478
TI  - Another postnatal-onset obesity syndrome.
AB  - We describe an apparently newly recognized postnatal-onset obesity syndrome with
      short stature, mental deficiency, hypogonadism, micropenis, contractures of the
      fingers, and cleft lip-palate. Comparison is made with other postnatal-onset
      obesity syndromes, particularly Vasquez syndrome and Urban syndrome. The cause of
      our patient's syndrome is unknown at present. We encourage the reporting of other
      cases to help clarify whether our patient represents a separate entity.

PMID- 8279479
TI  - Split hand/split foot anomaly in a family segregating a balanced translocation
      with breakpoint on 7q22.1.
AB  - An apparently balanced translocation, t(2;7)(q21.1;q22.1) was detected in a
      female patient with bilateral split hand and right split foot. Split hand/split
      foot (SHSF) segregated as an autosomal dominant character with low penetrance in
      her family. The translocation was present in 6 of 13 additional relatives
      investigated, one of whom also had split hand on right. This observation provides
      further confirmation of the presence of a locus for SHSF on 7q and narrows the
      critical region to band 7q22.1. Defects caused by alterations of this chromosome
      region are variable and include manifestations of both syndromal and non
      syndromal SHSF. Review of SHSF cases associated with chromosome 7 abnormalities
      showed a preferential involvement of the lower limbs and of the right side,
      suggesting the action of locally restricted developmental resistance mechanisms.

PMID- 8279480
TI  - Rod-cone dystrophy, sensorineural deafness, and renal dysfunction: an autosomal
      recessive syndrome?
AB  - An autosomal recessive syndrome of progressive rod-cone dystrophy, sensorineural
      deafness, and renal dysfunction was identified in 14 children in 9 Afrikaner
      families in South Africa. The renal involvement, which is of the Fanconi type,
      leads to rickets-like skeletal changes and kidney failure. Each of the children
      was initially misdiagnosed as having retinitis pigmentosa or Usher syndrome, on a
      basis of minor retinal pigmentation. This condition, which appears to be a
      hitherto undocumented entity, warrants differentiation from these disorders.

PMID- 8279481
TI  - Genetic skeletal dysplasias in the Museum of Pathological Anatomy, Vienna.
AB  - Skeletal material in the Museum of Pathological Anatomy, Vienna, has been
      appraised in order to modify existing descriptive designations and to establish
      diagnoses of specific genetic disorders. In this way osseous material relating to
      classical genetic syndromes has been identified and will be available for further
      study. Among the skeletons of adults in the museum, the following genetic
      conditions could be diagnosed: achondroplasia, Marfan syndrome, cleidocranial
      dysostosis, and diaphyseal aclasia. In adult sisters with dwarfism and a rickety
      bone disorder, the final diagnosis was uncertain. Infantile bone dysplasias,
      genetic conditions involving the skull, and malformation syndromes which are all
      represented in the museum are currently being analyzed.

PMID- 8279482
TI  - Prenatal detection of de novo paracentric inversion 46, XX inv (14) (q22q32.1) in
      a normal child: report and review of the literature.
AB  - We present prenatal diagnosis and follow-up examination of an individual with a
      de novo paracentric inversion of the long are of chromosome 14. A literature
      search documented 19 other cases of paracentric inversion of 14q. The outcome of
      each of these cases is specified together with that of this current case. Four of
      the 20 cases, all XY, manifested significant abnormalities with mental
      retardation and microcephaly present in 3 of the 4 cases; 15% (2/13) of familial
      cases had abnormalities and 40% (2/5) of de novo cases had abnormalities.

PMID- 8279483
TI  - Fetal alcohol syndrome in twins of alcoholic mothers: concordance of diagnosis
      and IQ.
AB  - The effects of teratogens can be modified by genetic differences in fetal
      susceptibility and resistance. Twins of alcoholic mothers provide a unique
      opportunity to study this phenomenon with respect to alcohol teratogenesis.
      Sixteen pairs of twins, 5 MZ and 11 DZ, all heavily exposed to alcohol
      prenatally, were evaluated. They represented all available twins of alcohol
      abusing mothers who were on the patient rolls of the authors. The rate of
      concordance for diagnosis was 5/5 for MZ and 7/11 for DZ twins. In two DZ pairs,
      one twin had fetal alcohol syndrome (FAS), while the other had fetal alcohol
      effects (FAE). In 2 other DZ pairs, one twin had no diagnosis while one had FAE.
      IQ scores were most similar within pairs of MZ twins and least similar within
      pairs of DZ twins discordant for diagnosis. Despite equivalent alcohol exposure
      within twin pairs, alcohol teratogenesis appears to be more uniformly expressed
      in MZ than in DZ twins. These data are interpreted as reflecting the modulating
      influence of genes in the expression of the teratogenic effects of alcohol.

PMID- 8279484
TI  - Pathogenesis of craniofacial and body wall malformations induced by ochratoxin A
      in mice.
AB  - Ochratoxin A (OA), a mycotoxin commonly found in soils and on moldy food such as
      cereal grains, is a potent teratogen. The present investigation was designed to
      examine the teratogenicity of OA administered acutely at early post-implantation
      stages in mice, with particular emphasis on the pathogenetic basis of induced
      malformations. Maternal OA administration on gestational day (GD) 7 or 8 resulted
      in excessive amounts of cell death in selected cell populations. After a single
      dose of 2-4 mg/kg, excessive cell death was notable within 6 hours, and persisted
      to 36 hours post-treatment. As observed in GD 14 or 18 fetuses, the spectrum of
      induced craniofacial malformations included exencephaly, midfacial clefting,
      cleft lip, as well as hypotelorism, and synophthalmia associated with
      holoprosencephaly. Body wall defects involved either the abdominal wall alone, or
      in combination with the thoracic wall, resulting in partial or complete exposure
      of the viscera. Potential mechanisms for OA-induced selective cell killing are
      discussed.

PMID- 8279485
TI  - Congenital malformation case reports: the editor's and reviewer's dilemma.

PMID- 8279486
TI  - Genetic contributions to quantitative lipoprotein traits associated with coronary
      artery disease: analysis of a large pedigree from the Bogalusa Heart Study.
AB  - A pedigree of a large family with high prevalence of heart disease is subjected
      to association and sib-pair linkage analysis to investigate the role of 5
      candidate genes in the regulation of lipoprotein metabolism and the development
      of coronary artery disease. At the 5% nominal significance level, the
      apolipoprotein B locus (APOB) was found to be linked to high-density lipoprotein
      cholesterol level (HDL-C), low-density lipoprotein cholesterol level (LDL-C), the
      ratio HDL-C/LDL-C, and apolipoprotein AI level times this ratio (apoAI x LDL
      C/HDL-C). APOB (PvuII) was strongly associated with apolipoprotein B levels
      (apoB) (P = 0.006) and the VNTR region of the APOB locus showed highly
      significant association between allele 7 and low triglyceride levels (P = 0.004).
      No significant linkage results were found with cholesterol ester transfer protein
      (CETP). At the 1% nominal significance level, CETP [TaqI(B)] showed significant
      association with LDL-C, apoB, and HDL-C/LDL-C. There was significant linkage of
      lipoprotein lipase (LPL) with very-low-density lipoprotein cholesterol and the
      ratio apoAI/HDL-C, and strong association results between LPL (HindIII) and
      triglyceride levels (P = 0.005). At the 5% nominal significance level,
      haptoglobin (HPA) was associated with HDL-C, HDL-C/LDL-C, apoAI/HDL-C and apoAI x
      LDL-C/HDL-C. The apolipoprotein AI locus did not show any significant linkages or
      associations. The study thus indicated that genetic variation of APOB, LPL, CETP,
      and lecithin cholesterol acyl transferase (which is linked to HPA and CETP) may
      play an important role in the regulation of lipoprotein metabolism and could
      contribute to the risk of coronary artery disease.

PMID- 8279487
TI  - Pathologic characterization of short-chain acyl-CoA dehydrogenase deficiency in
      BALB/cByJ mice.
AB  - BALB/cByJ mice have a deficiency of short-chain acyl-CoA dehydrogenase (SCAD) and
      are a useful model for studying the inborn errors of fatty acid metabolism which
      affect humans. Patients with some of these disorders present with hypoglycemia,
      hyperammonemia, and microvesicular fatty change of hepatocytes. In the present
      study we examined pathogen-free, SCAD deficient BALB/cByJ mice and control
      BALB/cBy mice for biochemical and tissue changes following fasting or salicylate
      challenge. We observed mitochondrial swelling and microvesicular fatty changes in
      hepatocytes in mutant mice, especially severe following a fast. However, fasting
      did not alter their blood ammonia and there was no apparent clinical disease.
      Similarly, salicylates did not produce disease in the BALB/cByJ mice. We did
      detect in mice an alternative pathway for salicylate metabolism, by-passing
      glycine conjugation which is the principal metabolic pathway in humans.

PMID- 8279488
TI  - Limb body wall complex: a critical review and a nosological proposal.
AB  - The analysis of the literature on limb body wall complex reveals a varied and
      rather confused spectrum of cases. However, we noticed the presence of at least 2
      clearly distinguishable phenotypes. The first phenotype shows craniofacial
      defects and amniotic bands and/or adhesion; the second--without craniofacial
      defects--presents urogenital anomalies, anal atresia, and abdominal placental
      attachment, together with a persistence of the extra-embryonic coelom. We think
      these 2 phenotypes are the consequence of different pathogenetic mechanisms. The
      pathogenesis of the first type can be related to an early vascular disruption,
      while the pathogenesis of the second one is attributable to an intrinsic
      embryonal maldevelopment. Eight cases of the second phenotype were identified and
      the pathological findings proving this maldevelopmental origin are described.

PMID- 8279489
TI  - Two additional cases of the Ohdo blepharophimosis syndrome.
AB  - Two additional cases of the Ohdo blepharophimosis syndrome are described and
      compared to the 5 patients previously reported. Blepharophimosis, ptosis, dental
      hypoplasia, mental retardation, and deafness can be considered as common
      manifestations of the syndrome. Male patients show cryptorchidism and scrotal
      hypoplasia.

PMID- 8279490
TI  - SHORT syndrome and insulin resistance.
AB  - We describe a further case of SHORT syndrome. This girl shows nearly all the
      typical manifestations reported in patients with SHORT syndrome. However, at 14
      years she presented with non-ketotic hyperglycemia. At 16 1/2 years, the
      diagnosis of diabetes mellitus secondary to severe insulin resistance was made by
      intravenous insulin challenge. Insulin resistant diabetes mellitus seems to be a
      new finding in SHORT syndrome, not previously described in this condition.

PMID- 8279491
TI  - Cleft lip (+/- cleft palate) in Danish twins, 1970-1990.
AB  - A classical twin study is one of the best methods to address the open question of
      the role of genes and environment in the cause of cleft lip with or without cleft
      palate [CL(P)]. In addition, when twin concordance rates are combined with
      information about the risk for CL(P) to more remote relatives, they can help to
      establish the most likely mode of inheritance for CL(P). The present study was
      based on three nation wide ascertainment sources of CL(P) in twins in Denmark
      during the period 1970-1990. The Danish surgical files were found suitable for
      ascertaining twins with non-syndromic CL(P) and a total of 39 pairs was
      identified through these files. In more than 70% of the cases, the zygosity
      assignment was based on unlike-sex or an extensive panel of blood, serum, and
      enzyme types. More mono- and dizygotic twin (CL(P) cases than expected were
      found, although the difference was not significant. The proband concordance rate
      for CL(P) was 60% in monozygotic twins and 10% in dizygotic twins; six cases were
      of unknown zygosity. This finding indicates that genetic factors play a major
      role in the cause of CL(P) but environmental and/or stochastic factors are
      probably acting too. When the familial recurrence patterns analyzed by Mitchell
      and Risch [1992: Am J Hum Genet 51:323-332] are interpreted in light of these new
      estimates of monozygotic concordance, they provide further evidence for the
      finding that no single locus can account for more than a six-fold increase in
      risk to first-degree relatives.

PMID- 8279492
TI  - Association of familial Duane anomaly and urogenital abnormalities with a
      bisatellited marker derived from chromosome 22.
AB  - We report a spectrum of defects that were found in an 18-year-old girl who
      presented for investigation of primary amenorrhea. The patient was found to have
      Duane anomaly, left renal agenesis, absent uterus, bilateral sensorineural
      deafness, and bilateral preauricular skin tags and sinuses. Investigation of her
      family showed that her brother also had Duane anomaly, right renal agenesis,
      sensorineural deafness, and preauricular skin tags and that their father had
      preauricular skin tags. Cytogenetic analysis, including in situ hybridisation of
      peripheral blood lymphocytes, demonstrated a supernumerary bisatellited marker
      chromosome derived from the region of chromosome 22pter-q11 in the affected
      individuals. Our findings indicate that a gene or genes located in the region of
      chromosome 22pter-q11 may be associated with the Duane anomaly and the
      development of the urogenital tract.

PMID- 8279494
TI  - 46,XY/46,XX mosaicism and congenital pulmonary lymphangiectasis with chylothorax.

PMID- 8279493
TI  - Uncombable hair, retinal pigmentary dystrophy, dental anomalies, and
      brachydactyly: report of a new patient with additional findings.
AB  - A new ectodermal dysplasia syndrome was reported by Bork et al. in 1987 (Hautarzt
      38:342-347). The syndrome consisted of hypotrichosis with the typical SEM
      (scanning electron microscopy) changes of uncombable hair, retinal pigmentary
      dystrophy, juvenile cataract, oligodontia, brachydactyly with brachymetacarpia;
      it was inherited as an autosomal dominant trait. We describe a sporadic case and
      add further clinical findings to expand the spectrum of this rare syndrome.

PMID- 8279495
TI  - Workstation robotics: a pilot study of a Desktop Vocational Assistant Robot.
AB  - Rehabilitation robots are increasingly being viewed as an appropriate assistive
      technology interface for persons with disabilities. The Desktop Vocational
      Assistant Robot (DeVAR) system is a voice-controlled robotic workstation designed
      to enable persons with severe mobility impairments to function independently in a
      work environment. This study examined the overall efficacy of the DeVAR system,
      the level of expertise required for therapist and support personnel, routine
      maintenance requirements, and the readiness of the device for a multicenter
      evaluation. Two precommercial DeVAR workstations were installed at selected
      sites. The pilot study spanned 8 months in which staff members and four subjects
      with high-level quadriplegia evaluated the systems extensively. Responses were
      generally favorable regarding ease of use and overall training process. Subjects
      recommended modifications, including incorporation of a noise cancellation
      microphone, more effective use of workstation space, and addition of vocational
      tasks. All respondents thought that if the recommended changes were implemented,
      DeVAR would have potential as a vocational assistant. The small number of
      subjects was due to the limited subject pool available for the study. On the
      basis of pilot results, the Veterans Administration Rehabilitation Research and
      Development Service, Baltimore, Maryland, is conducting a national multicenter
      evaluation to determine the overall utility and commercial readiness of the DeVAR
      system.

PMID- 8279496
TI  - Assistive technology and the newly disabled adult: adaptation to wheelchair use.
AB  - A naturalistic, ethnographic, phenomenological study of adaptation to wheelchair
      use was conducted with one key informant, a 30-year-old white man with acquired
      paraplegia who was undergoing acute rehabilitation. Primary staff members served
      as additional informants. It was found that adaptation to wheelchair use had both
      pragmatic and emotional components. The latter appeared in alternating phases of
      resistance and neutrality or detente. Therapist and patient had conflicting goals
      relative to wheelchair use, which occasioned considerable friction. The patient's
      initial attitudes regarding wheelchairs were prejudicial, which hampered his
      ability to see the chair as a useful tool for mobility and independence.
      Successful pragmatic adaptation hinged in part on emotional acceptance of the
      wheelchair.

PMID- 8279497
TI  - Comparison of computer interface devices for persons with severe physical
      disabilities.
AB  - This research employed a descriptive case study design to compare subjects'
      performance using three computer input devices: the Tongue Touch Keypad, the
      HeadMaster, and the mouthstick. The sample consisted of four students with severe
      physical disabilities enrolled in an adaptive computer class at a community
      college. Components of performance examined were input speed, accuracy, and level
      of perceived exertion. Subjects' acceptance of each of the interface devices was
      also examined. Results showed input speed to be the fastest with the mouthstick,
      followed by the HeadMaster and then the Tongue Touch Keypad. Accuracy of input
      did not vary significantly. Three subjects rated the Tongue Touch Keypad as
      requiring the lowest rate of perceived exertion, followed by the HeadMaster and
      then the mouthstick. Overall performance did not necessarily affect subjects'
      acceptability ratings of the devices. Information from this study will assist
      therapists in evaluating the effectiveness and desirability of computer interface
      devices for patients.

PMID- 8279498
TI  - Single-switch computer access for infants and toddlers.
AB  - Computer access was studied with children between the ages of 6 months and 18
      months with no known handicapping conditions. The research focused on determining
      at what age young children can access a computer using a single-switch system to
      run a simple cause-and-effect program. The sample consisted of 80 children
      divided into four groups (6 to 8 months, 9 to 11 months, 12 to 14 months, and 15
      to 17 months). Results demonstrated that some children as young as 6 months of
      age could control a computer-based, cause-and-effect program using a single
      switch access system. Therefore, professionals who work with children with
      disabilities may consider introducing computers to children at this age or to
      children who are functioning near this cognitive developmental level.

PMID- 8279499
TI  - The effect of word prediction on typing speed.

PMID- 8279500
TI  - Educating consumers about assistive technology.

PMID- 8279501
TI  - The fine line.

PMID- 8279502
TI  - The promise of assistive technology.

PMID- 8279503
TI  - The development of technology competencies and training guidelines for
      occupational therapists.
AB  - The ability to use technology has become a survival skill in our society. This
      paper discusses technology trends related to the demands of the Information Age,
      the increasing availability of information and assistive technologies, and the
      impact of recent civil rights legislation mandating that persons with
      disabilities be given equal access to technologies that can enhance functional
      performance. Occupational therapists must become competent in the application and
      integration of these technologies into reasonable accommodation interventions if
      we are to meet the changing needs of persons with disabilities. To address this
      need for technology training, a multitiered set of technology competencies
      specifically designed for occupational therapy practitioners was authored by the
      American Occupational Therapy Association Technology Special Interest Section and
      reviewed by occupational therapists with technology expertise. The process of
      developing these competencies and recommendations for implementing them within
      occupational therapy educational programs are discussed.

PMID- 8279504
TI  - Comparison of assistive device use and needs of home-based older persons with
      different impairments.
AB  - This paper examined assistive device use by noninstitutionalized older persons
      with visual, cognitive, and physical impairments. One hundred fifty seven persons
      over 60 years of age (M = 75.5 years) were interviewed in their homes for the
      University at Buffalo Rehabilitation Engineering Research Center Consumer
      Assessments Study. Subjects were assigned to one of seven groups according to
      types of impairment: minimal, physical, visual, visual and physical, cognitive,
      cognitive and physical, and cognitive and visual. Group assignments were based on
      scores on the Sickness Impact Profile (physical), Older Americans Resources and
      Services Program Multidimensional Functional Assessment Questionnaire (vision),
      and Mini Mental State Exam (cognitive). Overall, subjects owned a mean of 13.7
      devices, used 10.8 devices (79% of the devices they own), and were satisfied with
      9.8 devices (72% of the devices they own). There were significant differences
      among the impairment groups in numbers of devices owned and used, and in
      satisfaction with devices. Subjects expressed the need for more devices,
      especially devices for increasing mobility and assisting with balance. Results
      suggest a stronger role for occupational therapists in the assessment of
      assistive device needs of older persons, and in recommending devices and training
      persons in their use.

PMID- 8279505
TI  - Computer-assisted functional assessment and documentation.
AB  - Occupational therapy personnel spend considerable time on functional assessment
      and documentation. The rapid and error-free information processing ability of
      computers offers methods for data collection, clinical decision making, and
      reporting of functional assessment results, which may be more effective and
      efficient than the current paper-and-pencil methods. Computers can provide
      assistance throughout the many steps of the functional assessment and reporting
      process. Software is available to assist in direct data collection, data
      reduction, and analysis, or to assess complex data systems and databases.
      Additionally, computers can use assessment techniques, such as dynamic question
      sets and expert systems, which have not been possible with paper-and-pencil
      methods. Furthermore, data collected on computers are readily available to be
      integrated in computer-assisted report writing and can be compiled into large
      databases for analysis. These databases can be used for program evaluation,
      continuous quality improvement exercises, and other research objectives. This
      paper provides a snapshot of these computer uses in the assessment process.

PMID- 8279506
TI  - Addressing assistive technology needs in special education.
AB  - Assistive technology is critical to maximize the functional skills of the person
      with a physical disability at home, work, and school. As assistive devices become
      increasingly complex and expensive and more options are available, the need for
      an assistive technology specialist is enhanced. Recent regulations and advances
      in technology are affecting the type, quality, and comprehensiveness of assistive
      technology service provision and need for assistive technology specialists. The
      occupational therapist's role as an assistive technology specialist is
      illustrated in an example of an assistive technology program within a special
      education setting.

PMID- 8279507
TI  - Adaptive computer use for a person with visual impairment.
AB  - A single-subject research design that used multiple baselines across behaviors
      compared traditional adaptations (e.g., the use of readers) to adapted computer
      technologies for typical reading activities performed by an adult with severe
      visual impairment. A Macintosh IIci equipped with software that translated
      information displayed on the monitor into synthesized speech was paired with a
      page scanner and optical character recognition software to convert scanned images
      of printed text into computer documents. These computer technologies were applied
      to three reading behaviors: proofreading of word-processed documents, reading of
      printed research articles, and reading of common printed materials such as
      letters and instruction sheets. The findings demonstrated that the use of adapted
      computer technology, rather than traditional methods, increased the subject's
      reading efficiency and frequency. The increased functional independence that
      occurred as a result of the computer technology improved the subject's patterns
      of adaptation in reading-related tasks and improved the quality of her life.

PMID- 8279509
TI  - Threshold for force potentiation associated with skeletal myosin phosphorylation.
AB  - Phosphate incorporation by the phosphorylatable light chains (P-LC) of myosin is
      associated with isometric twitch force potentiation in intact fast-twitch muscle.
      The purpose of this study was to examine the association between myosin P-LC
      phosphorylation and force potentiation at higher stimulation frequencies (1-150
      Hz) using mouse extensor digitorum longus (EDL) muscles at 25 degrees C. Peak
      isometric force and the peak rate of isometric force development (+dF/dtmax) were
      measured at selected test frequencies before and after the application of a 5-Hz
      20-s conditioning stimulation known to increase P-LC phosphate content.
      Associated with a ninefold elevation in myosin P-LC phosphate content (to 0.72
      mol phosphate/mol P-LC), +dF/dtmax was increased at all test frequencies (mean
      27%, range 20-37%). After the conditioning stimulus, peak isometric force was
      increased by approximately 15% for frequencies 1-15 Hz. However, at 20-150 Hz,
      the increase in +dF/dtmax was not associated with force potentiation, since peak
      force was diminished by 5-40%. These data reveal that the stimulation frequency
      limit for the potentiation of peak force production associated with myosin P-LC
      phosphorylation is < 20 Hz in mouse EDL at 25 degrees C. Furthermore, the data
      suggest that increases in the rate constant describing the rate of cross-bridge
      transition from a non-force-generating to a force-generating state mediated by
      myosin P-LC phosphorylation may be responsible for the general increase in
      +dF/dtmax and for the force potentiation at 1-15 Hz.

PMID- 8279508
TI  - Regulation of renal cell organic osmolyte transport by tonicity.
AB  - Madin-Darby canine kidney cells accumulate several nonperturbing organic
      osmolytes when cultured in a hypertonic medium. Myo-inositol, betaine, and
      taurine are accumulated secondary to an increase in uptake, the first coupled to
      sodium entry, the latter two coupled to sodium and chloride entry. The transport
      rates increase as the result of an increase in maximum velocity for each
      cotransporter, with peak activity 24 h after the increase in tonicity. The cDNA
      for each cotransporter has been cloned. Their sequences indicate that the myo
      inositol cotransporter belongs to the gene family that includes the sodium
      coupled glucose transporter (SGLT1); the betaine and taurine cotransporters
      belong to the gene family of sodium- and chloride-coupled transporters that are
      responsible for neuronal uptake of many neurotransmitters. Assays of mRNA
      abundance and nuclear run-on assays reveal that shifts in tonicity have a major
      effect on transcription of the genes for the sodium-myo-inositol (SMIT) and
      sodium-chloride-betaine (BGT1) cotransporters. The ensuing increase in mRNA
      abundance for the two cotransporters and presumed increase in synthesis of the
      cotransporter proteins can explain the increase in transport activity in response
      to changes in tonicity.

PMID- 8279510
TI  - Role of nonselective cation current in muscarinic responses of canine colonic
      muscle.
AB  - The mechanism of muscarinic excitation was studied in colonic muscle strips and
      isolated cells. In whole cell voltage-clamp studies performed at 33 degrees C
      utilizing the permeabilized patch technique, acetylcholine (ACh) reduced an L
      type Ca2+ current. With K+ currents blocked, depolarization to positive
      potentials in the presence of ACh elicited outward current. Difference currents
      showed that ACh activated a voltage-dependent current that reversed at about -8
      mV; this current (IACh) had properties similar to the nonselective cation
      conductance found in other smooth muscle cells. The reversal potential of IACh
      shifted toward negative potentials when external Na+ was reduced, and the inward
      current elicited at -70 mV decreased when external Na+ was reduced. IACh was
      facilitated by internal Ca2+. After the current was activated at a holding
      potential of -70 mV, depolarizations to -30 to 0 mV elicited influx of Ca2+ via
      voltage-dependent Ca2+ channels. After repolarization to the holding potential, a
      large inward tail current was observed. IACh was blocked by Ni2+ and Cd2+ at
      concentrations of 100 microM or less. Quinine (0.5 mM) also blocked IACh. With
      the use of the sensitivity of IACh to reduced external Na+ and divalent cations,
      the role of IACh in responses of intact muscles to ACh was examined. When
      external Na+ was reduced, ACh failed to increase slow-wave duration, and Ni2+ (50
      microM) reversed the depolarization caused by ACh. These data suggest an
      important role for IACh in the electrical responses of colonic muscles. The
      contribution of IACh appears to prolong slow waves, which would allow greater
      entry of Ca2+ and increased force development.

PMID- 8279511
TI  - Extracellular ATP prevents the release of stored Ca2+ by autonomic agonists in
      rat submandibular gland acini.
AB  - In dose-dependent fashion, extracellular ATP reduces the increase in cytosolic
      Ca2+ concentration ([Ca2+]o) due to mobilization of cellular Ca2+ stores by both
      epinephrine [half-maximal inhibitory concentration (IC50) = 35.7 +/- 12.9 microM;
      Hill coefficient (NH) = -2.0 +/- 0.7, n = 8] and by carbachol (IC50 = 27.0 +/-
      7.0 microM, NH = -2.3 +/- 0.7, n = 9). Inhibition is due to ATP4- but does not
      result from any emptying or inaccessibility of Ca2+ stores, which are readily
      mobilized by thapsigargin in the presence of ATP4-. Reduction of Ca2+
      mobilization is rapid but is not due to direct interference by ATP with the
      interaction of carbachol or epinephrine with their respective cell surface
      receptors. A benzoyl derivative of ATP, 3'-O-(4-benzoyl) adenosine 5'
      triphosphate (BZATP) is more potent than ATP in reducing [Ca2+]i due to
      mobilization of stored Ca2+ by either carbachol or epinephrine (IC50 for
      carbachol = 3.9 +/- 0.4 microM, NH = -3.2 +/- 0.5; IC50 for epinephrine = 3.8 +/-
      0.2, NH = -2.6 +/- 0.7, n = 3) but GTP, UTP, ADP, and adenosine do not inhibit
      mobilization of stored Ca2+ by either carbachol or epinephrine. Neither ATP nor
      BZATP prevents the influx of extracellular Ca2+ stimulated by carbachol or
      epinephrine. These results suggest that ATP inhibits Ca2+ mobilization by
      autonomic neurotransmitters after occupation of P2Z purinoceptors.

PMID- 8279512
TI  - Influence of filter supports on transport characteristics of cultured A6 kidney
      cells.
AB  - Amphibian A6 kidney cells grown on Anocell filters developed a transepithelial
      potential difference of 37 mV, a short-circuit current (Isc) of 8 microA/cm2, and
      a resistance of 5 k omega.cm2. Other observations suggested a viable arginine
      vasopressin (AVP) V2 receptor-second messenger pathway in these cells: 1) AVP
      increased both an amiloride-sensitive Isc and adenosine 3',5'-cyclic
      monophosphate (cAMP) formation, and 2) scanning electron micrographs of A6 cells
      cultured on Anocell and ICN Cellagen filters demonstrated increased microvilli
      formation on the apical surface after AVP action. However, osmotic water flow
      (JV) across A6 cells on filter supports was not altered by either AVP or the
      permeable cAMP analogue dibutyryl cAMP (osmotic permeability coefficient = 2.5 x
      10(-3) cm/s). Diffusional water flow (Jdw) measured across A6 cells on Anocell
      filters using tritiated water (THO) ranged from 6 to 8 microliters.min-1.cm-2.
      Neither AVP nor the membrane-permeabilizing agents amphotericin B and digitonin
      were able to enhance unidirectional THO fluxes, although amphotericin B increased
      the Isc. These results suggested that there was an unknown barrier in series with
      the A6 cells limiting water flow. THO fluxes across filter supports, without an
      associated cellular monolayer, gave Jdw values in the range 7-30 microliters.min
      1.cm-2. Jv across the bare filter support was in the range of 0.3-1.5
      microliters.min-1.cm-2, similar to that measured in the presence of an A6
      monolayer. These observations suggest that the filter may be rate limiting for
      transepithelial water flow. Chloride fluxes across Anocell filters showed a
      stable value of 5 mu eq.h-1.cm-2. These observations exhibit the limitations of
      filter supports in the study of transport phenomena in cultured cells.

PMID- 8279513
TI  - Volume-sensitive anion channels mediate swelling-activated inositol and taurine
      efflux.
AB  - C6 glioma cells accumulate the organic osmolyte inositol in response to chronic
      hypertonic stress. Upon return to isotonic conditions, cell swelling activates a
      Na(+)-independent passive low-affinity inositol efflux mechanism that is
      inhibited 80-100% by a number of anion transport blockers, certain lipoxygenase
      blockers, and various polyunsaturated fatty acids. Taurine efflux is also
      enhanced by cell swelling. The taurine efflux pathway has characteristics that
      are identical to those of the inositol efflux mechanism, including kinetics of
      activation and inactivation, osmotic sensitivity, pharmacological sensitivity,
      and inhibition by certain Na+ and Cl- substitutes. These results suggest strongly
      that volume-sensitive inositol and taurine efflux are mediated by a common
      transport mechanism. The inhibition of the transport pathway by anion transport
      blockers and unsaturated fatty acids suggests indirectly that efflux of these
      solutes may be mediated by an anion channel. Whole cell patch clamp measurements
      in CsCl solutions were used to test this hypothesis. Under hypertonic conditions,
      C6 cells had an extremely low membrane conductance (approximately 0.02 nS/pF).
      After cell swelling, however, whole cell anion conductance was activated rapidly
      to values up to 1.5-2 nS/pF. This conductance was outwardly rectified and
      selective for anions and was inhibited 80-100% by blockers of swelling-activated
      inositol and taurine efflux. The relative taurine permeability (i.e.,
      Ptaurine/PCl) of the conductance was 0.20. Isosmotic replacement of raffinose in
      the external medium with inositol or sorbitol induced a transient inward current,
      suggesting that Cl- and these polyols compete for common binding sites on the
      channel. We conclude that a volume-sensitive anion channel mediates the efflux of
      structurally diverse organic osmolytes such as taurine and inositol from the
      cell.

PMID- 8279514
TI  - Control of intracellular calcium by membrane potential in human melanoma cells.
AB  - The modulation of intracellular calcium ([Ca2+]i) by the membrane potential was
      investigated in human melanoma cells by combining the nystatin-perforated patch
      clamp technique with Ca2+ measurements. Voltage steps to -100 mV induced a rise
      in [Ca2+]i and a creeping inward current. These effects were absent in Ca(2+)
      free solution and could be blocked by Ni2+ or La3+. Voltage ramps revealed a
      close correlation between [Ca2+]i and voltage, with the strongest voltage
      dependence around the resting potential. Long-lasting tail currents, closely
      correlated with the rise in [Ca2+]i and a reversal potential close to the K+
      equilibrium potential, occurred if the membrane potential was clamped back to 0
      mV. They were absent if intracellular K+ was replaced by Cs+ and blocked by
      extracellular tetraethylammonium (5 mM), Ba2+ (1 mM), or a membrane-permeable
      adenosine 3',5'-cyclic monophosphate analogue. These observations are discussed
      in relation to cell proliferation. The enhanced expression of K+ channels during
      cell proliferation provides a positive-feedback mechanism resulting in long-term
      changes in [Ca2+]i required for the G1-S transition in the cell cycle.

PMID- 8279515
TI  - Chemotaxis of newt eosinophils: calcium regulation of chemotactic response.
AB  - Local chemical events underlying chemotaxis were characterized in a new model
      cell, the newt eosinophil. These cells exhibit a chemotactic response to a
      trypsin-sensitive component of newt serum. Ca2+ plays a role in this process,
      since treatments expected to diminish Ca2+ availability from the medium [ethylene
      glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, Co2+, and
      verapamil], to break down transmembrane Ca2+ gradients (ionomycin), or to
      interfere with the function of intracellular Ca2+ stores (caffeine and neomycin)
      inhibited cell polarization and movement. Using imaging techniques we found that
      cytosolic Ca2+ concentration ([Ca2+]i) increased in response to newt serum.
      Migrating newt eosinophils exhibited a dynamic heterogeneous distribution of
      [Ca2+]i. [Ca2+]i was elevated in cells undergoing a change of direction relative
      to cells migrating persistently in one direction. Migrating cells contained
      gradients of [Ca2+]i along their long axis, with the front of the cell having
      consistently lower [Ca2+]i than the rear. When cells were loaded with the cell
      permeant form of fura 2, fura 2 acetoxymethyl ester, a caffeine-sensitive
      membrane-delimited region of elevated [Ca2+]i was seen associated with the
      microtubule organizing center. A model is proposed relating the distribution of
      [Ca2+]i and the location of the external stimulus to the generation and
      interaction of substances within the cell that both simulate and inhibit
      increases in [Ca2+]i.

PMID- 8279516
TI  - Phosphocreatine protects transgenic mouse liver expressing creatine kinase from
      hypoxia and ischemia.
AB  - Creatine kinase (CK) is normally found at high levels in muscle and brain and
      catalyzes the reaction phosphocreatine (PCr) + MgADP + H+<==>creatine (Cr) +
      MgATP. CK is not normally found at high levels in liver. A line of transgenic
      mice that express high levels of the BB-dimer of CK (CKB) in liver has allowed us
      to assess the role of CKB during periods of low oxygen stress. During 40 min of
      ischemia of normal perfused livers at 25 degrees C, ATP levels are depleted, and
      pH decreases to 6.6. pH recovers to a preischemic level after 30 min of
      reperfusion of normal livers; however, P(i) levels are significantly higher and
      ATP levels significantly lower than preischemic values. In transgenic liver with
      an initial PCr-to-ATP ratio of 4.5, ATP levels are maintained until PCr is
      markedly depleted. pH remains at preischemic levels for 16 min of ischemia of
      transgenic livers. During this length of ischemia in normal livers, pH has
      dropped to 6.9. pH, P(i), and ATP levels return to preischemic values within 30
      min of reperfusion in transgenic livers containing PCr and CK. During 90 min of
      hypoxia of normal perfused livers at 37 degrees C, ATP is depleted. After 15 min
      of hypoxia of normal livers, there is a significant increase in the release of
      lactate dehydrogenase (LDH). In transgenic livers, ATP is maintained, and no
      increase in LDH release is observed for up to 90 min, depending on the level of
      PCr before hypoxia. These results demonstrate the role of CKB in buffering ATP
      levels and regulating intracellular pH during periods of low oxygen
      stress.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279517
TI  - Characterization of the beta-subunit of the H(+)-K(+)-ATPase using an inhibitory
      monoclonal antibody.
AB  - The gastric proton pump, H(+)-K(+)-ATPase, is composed of alpha- and beta
      subunits. The 95-kDa alpha-subunit has been referred to as the catalytic subunit
      containing sites for ATP binding and phosphorylation. The beta-subunit is a
      glycoprotein with a 34-kDa core peptide that has a single transmembrane segment,
      a small cytoplasmic NH2-terminal, and a large extracellular COOH-terminal domain
      with seven potential N-linked glycosylation sites. To further study the beta
      subunit, we developed monoclonal antibodies that identified a 52-kDa mannose-rich
      glycoprotein that was deglycosylated by endoglycosidase H such that six transient
      intermediates were identified, as well as a 34-kDa beta-subunit core peptide.
      These observations suggest that the beta-subunit is synthesized as a 52-kDa
      glycoprotein with seven N-linked precursor high-mannose oligosaccharides that
      mature into complex oligosaccharides. One antibody, 2G11, inhibits the K(+)
      stimulated ATP hydrolysis as well as K(+)-stimulated p-nitrophenyl phosphatase
      (pNPPase) activity of the H(+)-K(+)-ATPase. Kinetic studies revealed that 2G11
      inhibited maximum velocity (Vmax) of ATP hydrolysis by approximately 50% with no
      change in the Km for K+, whereas, for pNPPase both Vmax and Km were altered.
      These studies demonstrate a functional role for the beta-subunit in the H(+)-K(+)
      ATPase activity, especially the K(+)-induced conformational states.

PMID- 8279518
TI  - GRP-preferring bombesin receptors increase generation of inositol phosphates and
      tension in rat myometrium.
AB  - In the estrogen-treated rat myometrium, bombesin (Bn) and related agonists
      triggered contraction and the increased generation of inositol phosphates. The
      relative order of potencies was identical for both responses: Bn = gastrin
      releasing peptide (GRP) = litorin = neuromedin C >> neuromedin B. Two specific
      GRP-preferring receptor antagonists, namely [D-Phe6]Bn-(6-13) methyl ester and
      [Leu14,psi 13-14]Bn were inhibitory for both Bn-mediated tension and generation
      of inositol phosphates. [125I-Tyr4]Bn bound to myometrial membranes with high
      affinity (Kd = 104 pM) to a single class of sites in a saturable and reversible
      manner. The relative potencies for inhibiting binding were GRP = litorin =
      [Tyr4]Bn (Ki = 0.4 to 0.6 nM) >> neuromedin B (Ki = 10.3 nM). The high affinity
      displayed by [D-Phe6]Bn-(6-13) methyl ester (Ki = 2.8 nM) and [Leu14,psi 13-14]Bn
      (Ki = 35 nM) for competing for [Tyr4]Bn binding supported the involvement of a
      GRP-preferring Bn receptor. Guanine nucleotides decreased the binding of [125I
      Tyr4]Bn and accelerated the rate of ligand dissociation, reflecting the coupling
      of receptors to guanine nucleotide regulatory proteins (G proteins). The results
      demonstrate that rat myometrium expresses functional GRP-preferring Bn receptors
      whose activation stimulates the phospholipase C pathway, pertussis toxin
      insensitive event that contributes to Bn-mediated uterine contractions.

PMID- 8279519
TI  - Association of the hepatic IP3 receptor with the plasma membrane: relevance to
      mode of action.
AB  - Studies were carried out to characterize the interaction between inositol 1,4,5
      trisphosphate (IP3) receptors and the plasma membrane fraction. Extraction of the
      membranes with the nonionic detergents Nonidet P-40 and Triton X-100, followed by
      centrifugation at 100,000 g, resulted in the doubling of the IP3 receptor in the
      pellets, whereas no detectable binding was found in the supernatants. These data
      indicate that the detergents did not solubilize the receptor, that it remained
      associated with membrane particles, and that it is likely to be associated with
      the cytoskeleton. The cytoskeleton proteins actin, ankyrin, and spectrin were
      identified in the plasma membrane fraction. However, comparison of the amount of
      these proteins in different fractions of the detergent, or otherwise treated
      plasma membrane fractions, showed no direct correlation between the presence of
      any of these proteins in the plasma membrane fraction and their ability to bind
      [3H]IP3. This is in contrast to the brain and T-lymphoma cells in which the IP3
      receptor is attached to ankyrin (L. Y. W. Bourguigon, H. Jin, N. Iida, N. R.
      Brandt, and S. H. Zhang. J. Biol. Chem. 268: 6477-6486, 1993; and S. K. Joseph
      and S. Samanta. J. Biol. Chem 268: 6477-6486, 1993). Thus the hepatic IP3
      receptor, which is different from the brain receptor, might attach to the
      cytoskeleton by anchoring to a different protein. Because cytochalasin D
      treatment of livers diminishes the ability of IP3 to raise cytosolic free Ca2+
      levels, the attachment of the IP3 receptor to the cytoskeleton seems to involve
      an association with microfilaments.

PMID- 8279520
TI  - Muscarinic stimulation of gallbladder epithelium. I. Electrophysiology and
      signaling mechanisms.
AB  - To understand the effects of acetylcholine (ACh) on fluid-absorbing epithelia, we
      carried out experiments on Necturus gallbladder epithelium. Binding studies with
      1-quinuclidinyl[phenyl-4(N)-3H]benzilate (QNB) demonstrated that Necturus
      gallbladder epithelial cells express high-affinity muscarinic receptors. The
      effects of ACh and carbachol were exerted from the basolateral surface and
      consisted of a transient hyperpolarization of both cell membranes and a
      concomitant decrease in the apparent fractional resistance of the apical
      membrane. Atropine blocked both effects. ACh also elicited transient elevations
      of inositol 1,4,5-trisphosphate and intracellular free calcium ([Ca2+]i) levels,
      the latter by both release from intracellular stores and basolateral influx. The
      phospholipase C antagonist U-73122 inhibited the effects of ACh, whereas
      inhibition of prostaglandin and guanosine 3',5'-cyclic monophosphate synthesis
      with indomethacin or methylene blue, respectively, had no effect. In conclusion,
      Necturus gallbladder epithelium expresses muscarinic receptors in the basolateral
      membrane. Receptor activation stimulates phospholipase C and elevates cellular
      levels of inositol 1,4,5-trisphosphate and [Ca2+]i. The elevation in [Ca2+]i
      activates K+ channels but apparently not Cl- channels.

PMID- 8279521
TI  - Muscarinic stimulation of gallbladder epithelium. II. Fluid transport, cell
      volume, and ion permeabilities.
AB  - Activation of muscarinic receptors in the fluid-absorptive epithelium of the
      Necturus gallbladder elevates cytosolic Ca2+ concentration, transiently
      hyperpolarizes the cell membrane voltages, and decreases the apparent fractional
      resistance of the apical membrane [G. A. Altenberg, M. Subramanyam, J. S.
      Bergmann, K. M. Johnson, and L. Reuss. Am. J. Physiol. 265 (Cell Physiol. 34):
      C1604-C1612, 1993]. In these studies, we show that at the peak of the
      hyperpolarization both apical and basolateral membrane resistances (Ra and Rb,
      respectively) decreased, but in 2-3 min Ra returned to control values while Rb
      rose to a level approximately 60% higher than control. The acetylcholine (ACh)
      induced decrease in Ra is caused by activation of apical membrane maxi K+
      channels secondary to elevation of cytosolic Ca2+ concentration. The increase in
      Rb is due to decreases in K+ and Cl- conductances. ACh had no effects on cell KCl
      content or water volume, although K+ conductance transiently increased. These
      results can be explained by the changes in basolateral membrane conductances. ACh
      did not alter fluid absorption. In conclusion, ACh has complex time-dependent
      effects on K+ and Cl- electrodiffusive permeabilities without measurable changes
      in cell volume or in the rate of transepithelial fluid transport.

PMID- 8279522
TI  - Effects of ATP and bradykinin on endothelial cell Ca2+ homeostasis and formation
      of cGMP and prostacyclin.
AB  - ATP and bradykinin are known to activate Ca2+ release from intracellular Ca2+
      pools as well as induce the influx of Ca2+ in many cell types. In adrenal medulla
      endothelial cells, we found that ATP and bradykinin could activate Ca2+ influx,
      although Ca2+ influx did not appear to be due to depletion of intracellular Ca2+
      pools per se, since depletion of intracellular Ca2+ pools with thapsigargin
      reduced rather than enhanced both unidirectional and steady-state 45Ca2+ uptake.
      In addition, Ca2+ influx, activated by ATP but not bradykinin, was mostly
      abolished after agonist removal in cells in which intracellular Ca2+ pools had
      not been allowed to refill, suggesting that continued receptor occupancy was
      necessary for ATP to activate Ca2+ influx. The role of Ca2+ in activating
      guanosine 3',5'-cyclic monophosphate (cGMP) formation [a marker for nitric oxide
      (NO) secretion] and prostacyclin (PGI2) secretion was also studied. Bradykinin
      induced cGMP and PGI2 formation and ATP-induced PGI2 formation each required Ca2+
      release from intracellular Ca2+ pools, since depletion of these pools with
      thapsigargin inhibited their formation. In contrast, ATP-induced cGMP formation,
      particularly at early time points, did not appear to require either Ca2+ release
      or Ca2+ influx. This suggests that ATP, but not bradykinin, either induces Ca(2+)
      independent NO formation or that ATP stimulates the generation of cGMP
      independently of NO. The latter supposition is supported by our observation that
      NO synthase inhibitors inhibited ATP-induced cGMP formation by at most 50%.

PMID- 8279523
TI  - Intracellular mechanism of Pb(2+)-induced norepinephrine release from bovine
      chromaffin cells.
AB  - The intracellular mechanism of Pb(2+)-induced release of norepinephrine (NE) was
      investigated in comparison with Ca2+ in bovine chromaffin cells permeabilized
      with staphylococcal alpha-toxin. Pb2+ activated NE release at considerably lower
      concentrations [concentration of free metal giving half maximal metal-dependent
      release (K0.5) 4.6 nM] than Ca2+ (K0.5 2.4 microM). The release of NE was
      associated with the release of dopamine-beta-hydroxylase but not lactate
      dehydrogenase. The maximal secretory responses produced by Pb2+ and Ca2+ were
      similar and nonadditive. Pb(2+)- and Ca(2+)-dependent releases showed a similar
      requirement for MgATP and were equally enhanced by protein kinase C activator 12
      O-tetradecanoylphorbol 13-acetate (TPA) but not by kinase A activator 8
      bromoadenosine 3',5'-cyclic monophosphate free base. The protein kinase C
      inhibitor staurosporine blocked the TPA-stimulated component of secretion but had
      no effect on the NE release in the absence of TPA. Calmidazolium, an inhibitor of
      calmodulin, inhibited the secretion evoked by both metals to similar extent.
      Agents interacting with microtubules (colchicine and vinblastine) or
      microfilaments (cytochalasin B and phalloidin) had no effect on secretion induced
      by either metal cation. These observations indicate that both Pb2+ and Ca2+ act
      at a common site and activate the exocytotic release of NE by an analogous
      mechanism.

PMID- 8279524
TI  - Modification of epithelial permeability by cationic polypeptides.
AB  - It has been demonstrated that protamine sulfate (PS; a cationic polypeptide
      composed of 70% arginine) increases the apical membrane conductance of the
      mammalian urinary bladder. In this report, synthetic cationic polypeptides (CpP;
      e.g., polyarginine) were used to determine whether the response of the bladder to
      PS was due to its cationic nature (i.e., its arginine content). We demonstrate
      that CpP induce a large increase in the cation and anion conductance of the
      apical membrane of the rabbit urinary bladder epithelium. The modulation of the
      membrane conductance by CpP is dependent upon a number of parameters. 1) The
      magnitude of the conductance change was voltage dependent. 2) An increase in the
      total charge per molecule increased the rate of conductance change. 3) An
      increase in the charge density (ratio of charged amino acids to total amino
      acids) increased the rate of change of conductance. 4) La3+ inhibited the ability
      of CpP to alter the membrane conductance. 5) The rate of reversal of the CpP
      induced conductance was dependent upon the total charge per molecule as well as
      the charge density. 6) The level of self-inhibition (ability of solution CpP to
      inhibit the CpP-induced membrane conductance) was inversely correlated with the
      charge density and was also concentration dependent, with less inhibition
      occurring at low mucosal CpP concentrations. These data are consistent with a
      model developed to describe the effect of PS on the conductive properties of the
      urinary bladder epithelium.

PMID- 8279525
TI  - ATP dependence of K-Cl cotransport in dog red blood cells.
AB  - Swelling-induced K-Cl cotransport in resealed dog red blood cell ghosts requires
      the presence of an ATP-generating system (G. C. Colclasure and J. C. Parker. J.
      Gen. Physiol. 100: 1-10, 1992). The present study shows that the endogenous
      adenine nucleotide present in the dog ghosts is sufficient to activate K-Cl
      cotransport, provided that creatine phosphate is incorporated in them. Creatine
      kinase is not required, because dog red blood cells, unlike those of humans,
      possess this enzyme. Although some ATP appears to be required for K-Cl
      cotransport by dog ghosts, an excess of this nucleotide is inhibitory. Creatine
      phosphate appears to play a special role in generating the ATP required for
      activation of K-Cl cotransport. If ghost ATP content is manipulated in the
      absence of creatine phosphate, by simply adding ATP to the hemolysate, no
      stimulation of K-Cl cotransport occurs. On the other hand, when creatine
      phosphate is present, K-Cl cotransport is activated. The results are discussed in
      relation to current views regarding the role of ATP in activation of K-Cl
      cotransport and the concept of the "phosphocreatine shuttle."

PMID- 8279526
TI  - Histamine H2 receptor mediates keratan sulfate secretion in rabbit chondrocytes:
      role of cAMP.
AB  - We obtained evidence for the presence of a single class of histamine H2 receptor
      on rabbit chondrocytes. Stimulation of these receptors with specific H2 agonists
      led to an inhibition of keratan sulfate secretion and rapid (15 min) accumulation
      of intracellular adenosine 3',5'-cyclic monophosphate (cAMP). Factors such as
      prostaglandin E2 and parathyroid hormone, which stimulate short-term increases in
      cAMP, also caused a reduction in keratan sulfate secretion. Conversely, cholera
      toxin and forskolin, which enhance cAMP accumulation over 48 and 4 h,
      respectively, as well as a continuous exposure to dibutyryl cAMP, stimulated
      keratan sulfate secretion. These data suggest that intracellular cAMP must be
      kept above a certain level for a prolonged period to stimulate keratan sulfate
      secretion. We conclude that inhibition of keratan sulfate secretion is coupled
      with activation of the H2 histamine receptor.

PMID- 8279527
TI  - Bombesin treatment enhances vasopressin receptors in Swiss 3T3 cells.
AB  - Cells possess receptors for multiple different peptides that regulate a wide
      spectrum of biological processes. Although examples of homologous and
      heterologous downregulation have been reported, relatively little is known about
      the interaction between different peptides in modulating cellular activities.
      Here we demonstrate that pretreatment of Swiss 3T3 fibroblasts with 10 nM
      bombesin for 48 h enhanced the 45Ca2+ efflux acutely stimulated by vasopressin.
      The effect was not reciprocal, since preincubation with vasopressin did not
      affect the bombesin-stimulated Ca2+ efflux. Measurement of displaceable [3H]
      vasopressin binding demonstrated that bombesin pretreatment increases the
      hormonal binding by 3.8 +/- 0.2-fold (SE; n = 14) measured at 37 degrees C or at
      4 degrees C. Scatchard analysis at 4 degrees C indicated that the increased
      binding reflects an increase in the number of vasopressin receptors without any
      significant effect on the apparent affinity of binding. Furthermore, addition of
      cycloheximide completely prevented the increase in [3H] vasopressin binding
      induced by bombesin. We conclude that long-term bombesin pretreatment induces
      heterologous enhancement of vasopressin responsiveness by increasing the number
      of membrane receptors.

PMID- 8279528
TI  - Specific decrease of mitochondrial thermogenic capacity in brown adipose tissue
      of obese SHR/N-cp rats.
AB  - The metabolic properties of brown adipose tissue (BAT), liver, and skeletal
      muscles were compared in lean and obese diabetic SHR/N-cp rats (a new model of
      type II diabetes) to test whether the severe insulin resistance of obese animals
      is specifically associated with a thermogenic defect in BAT. The respiratory
      response of brown adipocytes to norepinephrine and to agents bypassing the
      adenylate cyclase complex (dibutyryl cyclic AMP and palmitate) was decreased by
      two-thirds in obese rats, thereby indicating the presence of a major postreceptor
      defect. Significantly, total BAT cytochrome oxidase activity, uncoupling protein
      content, and mitochondrial guanosine 5'-diphosphate binding (3 indexes of BAT
      thermogenic capacity) were also decreased by two-thirds. The specific activities
      of these parameters expressed per total BAT mitochondrial protein were not
      altered either. This indicates that the total number of mitochondria per cell is
      decreased in BAT of obese rats. In contrast, total tissue cytochrome oxidase
      activity, protein content, and DNA content all increased by two to three times in
      the liver of obese SHR/N-cp rats, but these parameters remained unchanged in
      skeletal muscles (vastus lateralis and soleus). Such a remarkable liver
      hypertrophy may have occurred as a consequence of the persistent hyperphagia
      hyperinsulinemia of obese rats that induced a hyperplasia and/or a hepatocyte
      polyploidization. This observation together with the fact that daily energy
      expenditure associated with food intake was markedly increased in obese rats
      (representing as much as 25% of the total energy expenditure) strongly suggests
      that the liver plays a major role in energy balance in these animals.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279529
TI  - Ni2+ impairs thrombin-induced signal transduction by acting on the agonist and/or
      receptor in human platelets.
AB  - We have investigated the effect of NiCl2 on platelet activation induced by
      thrombin, phorbol 12-myristate 13-acetate, and calcium ionophores. Besides
      blocking Ca2+ influx, NiCl2 inhibited platelet aggregation, intracellular Ca2+
      mobilization, and phospholipase C activation induced by thrombin in a dose
      dependent manner. In contrast to ionomycin, NiCl2 completely blocked the platelet
      aggregation and intracellular Ca2+ mobilization induced by A23187. A23187 was not
      able to translocate Ni2+ across the plasma membrane. Ni2+ also inhibited phorbol
      myristate acetate-induced platelet aggregation. The results with staurosporine
      and low NiCl2 concentrations are in agreement in that increases in intracellular
      Ca2+ concentration and protein kinase C activation are necessary for full
      platelet activation mediated by thrombin.

PMID- 8279530
TI  - Intracellular free Ca2+ and vasoconstriction determined simultaneously in the
      perfused rat tail artery.
AB  - To measure, simultaneously, intracellular free Ca2+ ([Ca2+]i) and
      vasoconstriction in a perfused vessel, we used the fluorescent Ca2+ indicator
      fura 2 with a dual-wavelength excitation method. One-centimeter-long segments of
      the caudal artery were dissected from 12-mo-old male Wistar rats. The endothelium
      was removed by gentle rubbing. The artery was mounted in a specially constructed
      spectrofluorometer cuvette, perfused with oxygenated physiological saline
      solution at 37 degrees C, and loaded by perfusion with fura 2 acetoxymethyl ester
      (5 microM) over a 90-min period. This paper is a description of the technique and
      the experiments that validate it as a useful method for examining Ca(2+)-related
      vascular reactivity in an intact perfused vessel.

PMID- 8279531
TI  - Beat-to-beat measurements of [Ca2+]i and force in ferret cardiac muscle after
      chemical loading of aequorin.
AB  - This communication reports the development of a modified procedure for chemical
      loading of aequorin in small multicellular cardiac preparations, with special
      emphasis directed toward the implementation of a new method for computer
      controlled low-photon counting and digital processing and analysis of the data to
      obtain intracellular Ca2+ concentration ([Ca2+]i). In eight ferret right
      ventricular trabeculae, we measured the mechanical performance and found that, at
      1.25 mM extracellular Ca2+ concentration ([Ca2+]o), resting tension, developed
      tension, and time to peak tension were unchanged by the loading procedure.
      Estimated resting and peak systolic [Ca2+]i were 299 +/- 65 and 766 +/- 131 nM,
      respectively. Thirty minutes after raising the [Ca2+]o to 5 mM, there was a
      robust increase in mechanical performance, with peak systolic [Ca2+]i averaging
      1,218 +/- 222 nM. The diastolic [Ca2+]i remained unchanged. In four other
      trabeculae, exposure to a low-Na(+)-containing superfusate demonstrated a
      remarkable beat-to-beat correspondence of increases in diastolic [Ca2+]i and
      resting tensions. The same beat-to-beat concordance was also observed between the
      rapidly changing amplitudes of peak [Ca2+]i and developed tension. In additional
      experiments, simultaneous recordings of [Ca2+]i and force transients were
      obtained during rapid pace pause maneuvers. These studies showed distinct and
      quantifiable fluctuations of [Ca2+]i in a 1:1 relation to the mechanical record
      to a frequency of at approximately 300 beats/min. These results demonstrate that
      beat-to-beat measurements of [Ca2+]i and tension transients can be obtained with
      good resolution in multicellular cardiac preparations.

PMID- 8279532
TI  - Insulin increases the Na(+)-K(+)-ATPase alpha 2-subunit in the surface of rat
      skeletal muscle: morphological evidence.
AB  - The cellular localization of the alpha 2-subunit of the Na(+)-K(+)-ATPase was
      defined by immunoelectron microscopy, and the effect of insulin on the amount of
      alpha 2-immunoreactive subunits on the cell surface was quantitated. Two
      protocols were used for tissue fixation and immunolocalization. Protocol 1 was
      characterized by fixation with 2% paraformaldehyde, use of a monoclonal antibody,
      and detection with 3-nm-diameter gold-labeled Fab fragments or 10-nm gold-labeled
      immunoglobulin G. Protocol 2 was characterized by fixation with 4%
      paraformaldehyde plus 0.1% glutaraldehyde, use of a polyclonal antibody, and
      detection with 10-nm gold-labeled protein A. In control muscle, the alpha 2
      subunit of the Na(+)-K(+)-ATPase was present at the plasma membrane and in
      intracellular tubular and vesicular structures located in subsarcolemmal and
      triadic regions. Acute insulin stimulation increased the number of immunolabeled
      alpha 2-subunits in the plasma membrane after both fixation protocols. The gain
      in the plasma membrane ranged from 1.5- to 3.7-fold and was significant at the
      level of P < 0.005. These results provide morphological quantitative evidence
      that the alpha 2-subunit of the Na(+)-K(+)-ATPase is present both at the plasma
      membrane and intracellularly in mammalian skeletal muscle and that insulin
      acutely increases its abundance in the muscle surface.

PMID- 8279533
TI  - Muscarinic inhibition of ATP-sensitive K+ channels by protein kinase C in urinary
      bladder smooth muscle.
AB  - We explored the possibility that muscarinic receptor stimulation can inhibit ATP
      sensitive K+ (KATP) channels in smooth muscle cells from guinea pig urinary
      bladder. Whole cell K+ currents were measured in smooth muscle cells isolated
      from the detrusor muscle of the guinea pig bladder. Stimulation of muscarinic
      receptors by carbachol (CCh; 10 microM) inhibited KATP currents by 60.7%.
      Guanosine 5'-O-(2-thiodiphosphate) in the pipette (internal) solution prevented
      the CCh-induced inhibition of KATP currents. Activators of protein kinase C
      (PKC), a diacylglycerol analogue, and phorbol 12-myristate 13-acetate inhibited
      KATP currents by 63.5 and 73.9%, respectively. Blockers of PKC
      (bisindolylmaleimide GF-109203X and calphostin C) greatly reduced CCh inhibition
      of KATP currents. We propose that muscarinic receptor stimulation inhibits KATP
      channels in smooth muscle cells from urinary bladder through activation of PKC.

PMID- 8279534
TI  - Increased expression of Gi alpha 2 in mouse embryo stem cells promotes terminal
      differentiation to adipocytes.
AB  - The level of Gs alpha activity has been shown to modulate the rate of
      adipogenesis in mouse embryo fibroblast 3T3-L1 cells (H.-Y. Wang, D. C. Watkins,
      and C. C. Malbon. Nature Lond. 358: 334-337, 1992). For the current work the role
      of Gi alpha 2, a G protein mediator of inhibitory control of adenylyl cyclase, in
      regulating terminal differentiation of these cells was explored by stable
      transfection of fibroblasts expressing wild-type and a constitutively active
      mutant of Gi alpha 2 (Q205L). Under the influence of the cytomegalovirus
      promoter, the expression vector yielded a 1.7-fold (Q205L mutant Gi alpha 2) and
      2.2-fold (wild-type Gi alpha 2) increase in steady-state levels of these G
      protein alpha-subunits. Elevation of Gi alpha 2 expression or expression of
      constitutively active Gi alpha 2 (Q205L) promoted lipid accumulation in these
      clones, the hallmark of terminal differentiation of 3T3-L1 fibroblasts to
      adipocytes. Increasing Gi alpha 2 activity promotes adipogenic conversion, as was
      previously observed by decreasing Gs alpha either by inducers of differentiation
      or by oligodeoxynucleotides antisense to Gs alpha. Thus Gs alpha and Gi alpha 2
      are shown to be counterregulatory with respect to promoting differentiation of
      3T3-L1 mouse embryo fibroblasts to adipocytes in the absence of exogenously added
      inducers of differentiation. This is the first report demonstrating the induction
      of terminal differentiation of cells by the overexpression of a G protein alpha
      subunit, further implicating G proteins as regulators of complex biological
      responses such as adipogenesis.

PMID- 8279535
TI  - Lack of effect of hyperglycemia on lipolysis in humans.
AB  - To examine whether hyperglycemia is an independent regulator of adipose tissue
      lipolysis, we measured palmitate flux ([3H]palmitate) on two occasions in eight
      volunteers with insulin-dependent diabetes. On one. occasion, euglycemia was
      maintained for 4 h continuously; on a different occasion, hyperglycemia (plasma
      glucose, 12 mmol/l) was induced after 2 h of euglycemia. Palmitate flux decreased
      from 1.39 +/- 0.22 to 1.25 +/- 0.18 mumol.kg-1 x min-1 during sustained
      euglycemia and from 1.43 +/- 0.24 to 1.13 +/- 0.19 mumol.kg-1 x min-1 during the
      transition from the euglycemic to the hyperglycemic study intervals. There were
      no significant differences between the changes in palmitate flux from the first
      to the second study interval on the control (euglycemia-euglycemia) and
      experimental (euglycemia-hyperglycemia) study days and no difference between
      palmitate flux on different study days. Thus, in the face of euinsulinemia,
      euglucagonemia, and the absence of somatostatin, no effect of hyperglycemia on
      free fatty acid metabolism could be detected in humans.

PMID- 8279536
TI  - Differential effects of corticosteroids on rat peripheral blood T-lymphocyte
      mitogenesis in vivo and in vitro.
AB  - The effects of corticosteroids were studied on the concanavalin A (Con A)-induced
      mitogenesis of peripheral blood T-lymphocytes obtained from intact and
      adrenalectomized (ADX) Wistar rats. One week of adrenalectomy reduced the
      proliferative response of T-cells by 65% compared with sham-operated controls.
      Substitution of ADX rats with subcutaneously implanted 12.5-mg corticosterone
      (Cort) pellets, which resulted in low circulating Cort levels (17 +/- 3 nM),
      restored the reduced proliferative capacity to that of sham-ADX animals. In
      contrast, T-lymphocyte proliferation was nearly absent in ADX rats substituted
      with high circulating Cort levels (173 +/- 15 nM; 100-mg Cort pellet). In vitro,
      Cort suppressed the mitogenic response of T-lymphocytes from ADX and sham-ADX
      animals. The glucocorticoid antagonist RU-486 (500 nM) completely blocked this
      suppressive effect. However, a 10 times lower concentration of RU-486 reversed
      the effects of a low (10 nM) Cort concentration from suppression to stimulation.
      It is concluded that high Cort concentrations in vivo and in vitro suppressed T
      lymphocyte mitogenesis but that low concentrations in vivo were stimulatory,
      whereas this stimulation in vitro occurred only in the presence of
      antiglucocorticoids. These opposing effects of Cort emphasize a bimodal
      regulatory role of this hormone in immune regulation that may be mediated by
      different corticosteroid receptors.

PMID- 8279537
TI  - Effects of recombinant human IGF-I on glucose and leucine kinetics in men.
AB  - To examine the effects of recombinant human (rh) insulin-like growth factor I
      (IGF-I), insulin, and saline on metabolic parameters, we studied 20 young
      nonobese healthy men. Euglycemic clamps with 240-min IGF-I infusions at two doses
      (49 and 33 pmol.kg-1 x min-1, n = 8 and 12 subjects) were performed and compared
      with hyperinsulinemic-euglycemic clamps (2.25 pmol.kg-1 x min-1, n = 9). Leucine
      and glucose kinetics were examined with L-[1-13C]leucine and [3-3H]glucose.
      Glucose rate of appearance (Ra) declined equivalently in the 49 pmol.kg-1.min-1
      IGF-I and insulin clamps but remained at basal levels during the 33 pmol.kg-1 x
      min-1 IGF-I infusions. In contrast, Rd of glucose was increased by 176% in the 49
      pmol.kg-1 x min-1 IGF-I and 78% in the 33 pmol.kg-1 x min-1 IGF-I infusions.
      Furthermore, to prevent hypoglycemia after the termination of both rhIGF-I
      infusions, it was necessary to infuse glucose for an additional 2-20 h. Ra of
      leucine was suppressed significantly by both IGF-I and insulin, whereas leucine
      oxidation was not affected by either hormone. Therefore, the rate of
      disappearance of leucine expressed as the difference between Ra and oxidation
      rates was significantly reduced in all clamps. In addition, IGF-I significantly
      suppressed beta-cell secretion without affecting the other glucoregulatory
      hormones. In contrast to insulin, IGF-I had no apparent effect on lipolysis, as
      measured by changes in nonesterified fatty acids.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8279538
TI  - Mechanism of oxidative stress in skeletal muscle atrophied by immobilization.
AB  - To clarify the mechanism of oxidative stress in skeletal muscle atrophied by
      immobilization, we measured the activities of antioxidant enzymes and xanthine
      oxidase (XOD) and carried out the cytochemical study of hydrogen peroxide in a
      typical slow red muscle, the soleus. Male Wistar rats (15 wk old), of which ankle
      joints of one hindlimb were immobilized in the fully extended position, were
      killed after 4, 8, or 12 days. The activities of Mn-containing superoxide
      dismutase (Mn-SOD), Cu-Zn-containing superoxide dismutase (Cu-Zn-SOD), Se
      dependent glutathione peroxidase (Se-GSHPx), glutathione S-transferase, catalase,
      and glutathione reductase were measured spectrophotometrically. The XOD activity
      and the concentrations of hypoxanthine, xanthine, and urate were measured using a
      high-performance liquid chromatography. The cytochemical study of hydrogen
      peroxide in short-term organ culture was performed using an electron microscope.
      Increased Cu-Zn-SOD and decreased Mn-SOD in atrophy might reflect increased
      generation of superoxide anions in the cytoplasm rather than in the mitochondria.
      The source of superoxide anions in the cytoplasm might be the increased
      superoxide-producing XOD. Enhanced generation of superoxide anions and increased
      Cu-Zn-SOD activity in atrophy suggested the enhanced generation of hydrogen
      peroxide in the cytoplasm. Due to the unchanged activity of Se-GSHPx and the
      unchanged or slightly increased activity of catalase in atrophy, the ability to
      degrade hydrogen peroxide might not increase so much. Hence, hydrogen peroxide is
      expected to be increased in atrophy. The cytochemical study supported this
      expectation.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279539
TI  - Temporal changes in insulin resistance and secretion in 24-h-fasted conscious
      pregnant rats.
AB  - To determine the temporal sequence of pregnancy-induced changes in insulin action
      and secretion, awake midpregnant (11-12 days) and late pregnant (19-20 days) rats
      underwent a two-step euglycemic hyperinsulinemic or a hyperglycemic clamp study
      after a 24-h fast. During euglycemia, insulin-stimulated increments in glucose
      uptake and clearance in midpregnant rats were reduced by 60-70% at the lower dose
      (insulin approximately 360 pM) and by 20-30% at the higher dose (insulin
      approximately 1,750 pM; P < 0.01 vs. virgin controls). Insulin action was also
      diminished in late pregnant rats. However, the magnitude of resistance did not
      increase. Insulin-mediated suppression of glucose production was only minimally
      impaired in midpregnancy. In contrast, glucose production was virtually unchanged
      in late pregnancy, even at the highest insulin dose. During hyperglycemia,
      insulin responses in late pregnancy were markedly increased 5-fold above controls
      and 2.5-fold above midpregnant rats (P < 0.05). We conclude that rat pregnancy is
      characterized by the early appearance of peripheral insulin resistance. As
      pregnancy progresses toward term, marked hepatic insulin resistance and insulin
      hypersecretion develop, whereas peripheral insulin resistance demonstrates
      negligible changes. These data imply that insulin hypersecretion during late
      pregnancy is most closely linked to hepatic insulin resistance, at least in 24-h
      fasted animals.

PMID- 8279540
TI  - Regulation of fat-carbohydrate interaction in skeletal muscle during intense
      aerobic cycling.
AB  - Six male subjects received either a saline (control) or Intralipid infusion
      during 30 min rest and 15 min cycling at 85% maximal O2 uptake (VO2max) to
      examine the regulation of fat-carbohydrate interaction (glucose-fatty acid cycle)
      in skeletal muscle. Muscle biopsies were sampled immediately before and at 3 and
      15 min of exercise in both trials. A muscle biopsy was also taken at -30 min rest
      in the Intralipid trial. Intralipid infusion significantly elevated plasma free
      fatty acids above control during rest (0.21 +/- 0.04 to 0.94 +/- 0.09 mM) and
      exercise (5 min: 1.27 +/- 0.15 mM; 15 min: 1.42 +/- 0.13 mM). Muscle glycogen
      degradation was significantly lower in the Intralipid trial (109.7 +/- 29.3 vs.
      194.7 +/- 32.1 mmol/kg dry muscle). Muscle lactate accumulation after 15 min was
      similar in both trials (control, 60.7 +/- 12.2 and Intralipid, 60.9 +/- 12.4
      mmol/kg dry muscle). Muscle citrate increased at rest during Intralipid (0.32 +/-
      0.06 to 0.58 +/- 0.06 mmol/kg dry muscle) but was not different between trials at
      3 min (control, 0.73 +/- 0.07 and Intralipid, 0.68 +/- 0.06 mmol/kg dry muscle)
      and 15 min of cycling. Resting acetyl-CoA was unaffected by Intralipid and
      increased similarly in both trials at 3 min of cycling (control, 59.0 +/- 10.3
      and Intralipid, 50.7 +/- 13.6 mumol/kg dry muscle) and remained unchanged at 15
      min. Pyruvate dehydrogenase activity increased five- to sevenfold during exercise
      and was similar in both trials (15 min: control, 2.42 +/- 0.30 and Intralipid,
      2.79 +/- 0.41 mmol.min-1 x kg wet wt-1).(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279541
TI  - Role of angiotensin II in brown adipose thermogenesis during cold acclimation.
AB  - The role of angiotensin II (ANG II) in increased sympathetic neuroeffector
      mechanisms observed in cold-induced thermogenesis of brown adipose tissue (BAT)
      was examined. Cold exposure (4 degrees C) for 7 days resulted in an increase in
      interscapular fat (ISF) ANG II content expressed per gram wet weight or per lobe
      of ISF, without concomitant changes in plasma components of the renin-angiotensin
      system. Additionally, in ISF slices preloaded with [3H]norepinephrine (NE), ANG
      II (10 nM) resulted in an increase (3-fold) in evoked 3H overflow from ISF slices
      from cold-exposed rats compared with ambient temperature controls. However,
      although basal 3H outflow was increased (2-fold) in ISF slices from cold-exposed
      rats, evoked 3H overflow was not different between ISF slices from cold-exposed
      and control rats. Specific neuronal uptake of [3H]NE in ISF slices from cold
      exposed rats was decreased by 64%. Administration of the non-peptide AT1-receptor
      antagonist losartan to cold-exposed rats resulted in complete inhibition of ANG
      II-mediated presynaptic facilitation of evoked 3H overflow from ISF slices.
      However, losartan administration had no effect on cold-induced increases in ANG
      II content, protein content, and decreases in neuronal [3H]NE uptake in ISF.
      Results from these studies suggest that cold-induced thermogenesis of BAT results
      in alterations in presynaptic ANG II facilitation of NE release and defects in
      removal of NE from the synaptic cleft (neuronal uptake), both of which would
      enhance sympathetic nervous system-mediated thermogenesis. Furthermore, these
      results demonstrate a role for ANG II in enhanced sympathetic activity of cold
      induced thermogenesis in BAT.

PMID- 8279542
TI  - Mammalian bombesin as a hormone in ovine pregnancy: ontogeny, origin, and
      molecular forms.
AB  - Mammalian gastrin-releasing peptides (GRP) are present in female reproductive
      tissues and stimulate uterine contraction and DNA synthesis in the endometrium.
      We set out to establish whether the GRP were likely to play a role in fetal
      development by measuring the fetal and maternal plasma concentrations in
      chronically cannulated fetal sheep from 115 days gestation to term (145 days) and
      for 18 days after parturition. Placental fluids and fetal urine were also
      obtained. In a separate series of animals, uterine, placental, and fetal gut and
      lung tissues were collected. Samples were extracted in acid and assayed by
      radioimmunoassay, and molecular forms were characterized by high-performance
      liquid chromatography. GRP were present in the decidua (> 10 pmol/g), as well as
      placental, uterine, lung, and gastrointestinal tissues (all < 6 pmol/g). Fetal
      and maternal plasma GRP were elevated compared with nonpregnant ewes, falling
      sharply after parturition. Placental fluids and urine also contained GRP (80-410
      fmol/ml). The main molecular form in all tissues and fluids examined coeluted
      with porcine GRP-(18-27). GRP immunoreactivity was primarily localized to
      epithelial cells of the decidua. These data suggest that plasma GRP is probably
      derived from the decidua and may play a role as a circulating hormone in ovine
      fetal and uterine development.

PMID- 8279543
TI  - Lipoprotein lipase binding to adipocytes: evidence for the presence of a heparin
      sensitive binding protein.
AB  - Lipoprotein lipase (LPL) is synthesized by adipocytes, associated with the cell
      surface, and released from the cells when they are treated with heparin. Release
      of LPL from the adipocyte is required for LPL to migrate to its physiological
      site of action on the luminal surface of capillary endothelial cells. To better
      understand this process, we studied the interaction of LPL with adipocyte cell
      membrane proteins. With the use of a ligand blot method, LPL specifically bound
      to a heparin-releasable, 116-kDa protein on mouse-derived brown fat adipose cell
      (BFC-1 beta) and rat adipocyte membranes. A 116-kDa cell surface protein was
      metabolically labeled with [35S]methionine and bound to LPL-Sepharose. This
      suggested that the LPL-binding protein was synthesized by the cells. When BFC-1
      beta were treated with heparin to eliminate heparin-sensitive cell surface
      binding sites, LPL binding to the cells decreased and release of newly
      synthesized LPL activity increased. 125I-labeled LPL binding to control cells was
      reduced (> 70%) by a 50-fold excess of unlabeled LPL. The residual LPL binding to
      heparin-treated cells was, however, not decreased by the addition of unlabeled
      LPL. These data imply that specific adipocyte surface LPL binding involves
      heparin-sensitive sites. We hypothesize that the heparin-releasable, 116-kDa LPL
      binding protein mediates specific LPL binding to adipocytes and that LPL activity
      within adipose tissue is regulated, in part, by the interaction of LPL with this
      binding protein.

PMID- 8279544
TI  - GLUT-4 content in plasma membrane of muscle from patients with non-insulin
      dependent diabetes mellitus.
AB  - The abundance of GLUT-4 protein in both total crude membrane and plasma membrane
      fractions of vastus lateralis muscle from 13 obese non-insulin-dependent diabetes
      mellitus (NIDDM) patients and 14 healthy subjects were examined in the fasting
      state and after supraphysiological hyperinsulinemia. In the basal state the
      immunoreactive mass of GLUT-4 protein both in the crude membrane preparation and
      in the plasma membrane fraction was similar in NIDDM patients and control
      subjects. Moreover, in vivo insulin exposure neither for 30 min nor for 4 h had
      any impact on the content of GLUT-4 protein in plasma membranes. With the use of
      the same methodology, antibody, and achieving the same degree of plasma membrane
      purification and recovery, we found, however, that intraperitoneal administration
      of insulin to 7-wk-old rats within 30 min increased the content of GLUT-4 protein
      more than twofold (P < 0.01) in the plasma membrane from red gastrocnemius and
      soleus muscle. In conclusion, when the subcellular fractionation method was
      applied to human muscle biopsies taken in the basal state, no difference could be
      found in the plasma membrane content of immunoreactive GLUT-4 protein between
      NIDDM patients and normal subjects. With this technique, we were unable to show
      evidence for a regulatory effect of insulin on the plasma membrane level of GLUT
      4 protein in human muscle.

PMID- 8279545
TI  - Differential regulation of intracellular glucose metabolism by glucose and
      insulin in human muscle.
AB  - Insulin and glucose stimulate glucose uptake in human muscle by different
      mechanisms. Insulin has well-known effects on glucose transport, glycogen
      synthesis, and glucose oxidation, but the effects of hyperglycemia on the
      intracellular routing of glucose are less well characterized. We used euglycemic
      and hyperglycemic clamps with leg balance measurements to determine how
      hyperglycemia affects skeletal muscle glucose storage, glycolysis, and glucose
      oxidation in normal human subjects. Glycogen synthase (GS) and pyruvate
      dehydrogenase complex (PDHC) activities were determined using muscle biopsies.
      During basal insulin replacement, hyperglycemia (11.6 +/- 0.31 mM) increased leg
      muscle glucose uptake (0.522 +/- 0.129 vs. 0.261 +/- 0.071 mumol.min-1 x 100 ml
      leg tissue-1, P < 0.05), storage (0.159 +/- 0.082 vs. -0.061 +/- 0.055, P <
      0.05), and oxidation (0.409 +/- 0.080 vs. 0.243 +/- 0.085, P < 0.05) compared
      with euglycemia (6.63 +/- 0.33 mM). The increase in basal glucose oxidation due
      to hyperglycemia was associated with increased muscle PDHC activity (0.499 +/-
      0.087 vs. 0.276 +/- 0.049, P < 0.05). However, the increase in leg glucose
      storage was not accompanied by an increase in muscle GS activity. During
      hyperinsulinemia, hyperglycemia (11.9 +/- 0.49 mM) also caused an additional
      increase in leg glucose uptake over euglycemia (6.14 +/- 0.42 mM) alone (5.75 +/-
      1.25 vs. 3.75 +/- 0.58 mumol.min-1 x 100 ml leg-1, P < 0.05). In this case the
      major intracellular effect of hyperglycemia was to increase glucose storage (5.03
      +/- 1.16 vs. 2.39 +/- 0.37, P < 0.05). At hyperinsulinemia, hyperglycemia had no
      effect on muscle GS or PDHC activity.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279546
TI  - Linear V1-vascular vasopressin antagonists suitable for radioiodination,
      biotinylation, and fluorescent labeling.
AB  - We modified several linear V1-vascular arginine vasopressin (AVP) antagonists to
      obtain compounds suitable for radioiodination, biotinylation, and fluorescent
      labeling. In binding competition experiments with human platelet V1-vascular AVP
      receptors, the linear V1 antagonist phenylacetyl-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro
      Arg-NH2 (PhaaGln) displayed the greatest affinity [dissociation constant (Kd) =
      0.05 +/- 0.01 nM]. The radioiodinated compound phenylacetyl-D-Tyr(Et)-Phe-Val-Asn
      Lys-Pro-125I-labeled Tyr-NH2 (125I-labeled TyrPhaa) was characterized by a high
      affinity (Kd = 1.42 +/- 0.19 nM), a low nonspecific binding, and good stability.
      PhaaGln coupled to dodecabiotin retained a good affinity for V1-vascular AVP
      receptors (Kd = 1.41 +/- 0.20 nM). The complex PhaaGln-dodecabiotin-avidin is
      bifunctional, since an avidin-agarose column specifically bound V1-vascular AVP
      receptors labeled with 125I-TyrPhaa-dodecabiotin. In A7r5 vascular smooth muscle
      cells loaded with fura-2, PhaaGln and PhaaGln-dodecabiotin were pure antagonists
      as they blocked AVP-induced calcium mobilization but did not elicit a calcium
      signal by themselves. V1-vascular AVP receptors of A7r5 vascular smooth muscle
      cells were visualized by bound PhaaGln-dodecabiotin made fluorescent by labeling
      with fluorescein avidin. Thus linear V1-vascular AVP antagonists can be used as
      high affinity and specificity radioiodinated, biotinylated, and fluorescent
      probes to explore V1-vascular AVP receptors of human and animal origin.

PMID- 8279547
TI  - High Km of GLUT-2 glucose transporter does not explain its role in insulin
      secretion.
AB  - Evidence indicates that the high-Km GLUT-2 function of the islet cells is
      essential for insulin secretion in response to glucose. To examine possible
      significance of the high-Km transport function of GLUT-2 in this secretory
      response, we have studied by computer simulation the effects of high- and low-Km
      glucose uptake on the steady-state intracellular glucose concentration and
      glucose phosphorylation in beta-cells. Our computations reveal that both the
      intracellular glucose concentration and the glucose phosphorylation catalyzed by
      glucokinase increase significantly as the extracellular glucose concentration
      increases from 5 to 20 mM, even with a transport Km as low as 1.5 mM, the lowest
      value known for GLUT-1. Our results indicate that the apparent requirement of
      GLUT-2 for glucose-sensitive insulin secretion cannot be explained simply by its
      high-Km transport function alone and suggest that an isoform-specific, direct
      coupling of GLUT-2 with a certain glycolytic enzyme, such as glucokinase, is
      essential for the secretory response.

PMID- 8279548
TI  - Effects of endotoxin on pigs prefed omega-3 vs. omega-6 fatty acid-enriched
      diets.
AB  - We investigated in a porcine model whether omega-3 fatty acids modify the
      physiological response to sepsis. For 8 days, 16 male pigs were fed a diet
      containing 18% fat by weight enriched with either omega-3 or omega-6 fatty acids
      (FA). A group of six pigs receiving their regular diet served as controls. The
      omega-3 FA-supplemented pigs had elevated levels of omega-3 FA in their serum
      free FA, serum phospholipid (PL), and platelet PL levels compared with either of
      the other groups. On the ninth day, the unanesthetized pigs were injected with
      0.3 mg/kg of endotoxin (Escherichia coli) intravenously. The animals had a
      significant decrease in their arterial O2 pressure (PaO2) [from 84.4 +/- 6.8 (SD)
      to 64 +/- 9.4, and from 83.1 +/- 7.2 to 55.9 +/- 6.3 mmHg in the omega-6 FA and
      regular diet groups, respectively]. The PaO2 did not decrease in the omega-3 FA
      pigs. The omega-3 FA group had significantly lower pulmonary vascular resistance
      (541 +/- 205 dyn.s.cm-5) 20 min after endotoxin compared with either the omega-6
      FA or regular diet groups (797 +/- 233 and 1,102 +/- 552 dyn.s.cm-5,
      respectively) and more normal blood pressure compared with the other two groups.
      Plasma thromboxane (Tx) B2 and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)
      levels were lowest in the omega-3 FA diet group and highest in the regular diet
      group.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279549
TI  - Androgen regulation of thromboxane A2/prostaglandin H2 receptor expression in
      human erythroleukemia cells.
AB  - Thromboxane A2 (TxA2), a platelet aggregator and vasoconstrictor, has been
      implicated as a potential mediator of cardiovascular diseases. Abuse of
      androgenic steroids has been associated with thrombotic cardiovascular diseases.
      Human erythroleukemia (HEL) cells, a megakaryocyte-like cell line, express
      functional TxA2/prostaglandin H2 (PGH2) receptors with characteristics similar to
      those seen in platelets. This study characterized testosterone regulation of HEL
      cell TxA2/PGH2 receptors. TxA2/PGH2 receptor affinity (Kd) and density (Bmax)
      were determined via equilibrium binding experiments using the radiolabeled TxA2
      mimetic (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-2-yl)-5-he ptenoic acid (125I
      labeled BOP). Testosterone (200 nM) but not estradiol increased Bmax from 108 +/-
      9 fmol/mg protein to 157 +/- 9 fmol/mg protein (n = 7 experiments; P < 0.01)
      without any significant change in Kd. Testosterone had no significant effect on
      alpha 2-adrenergic receptor density. The maximum increase in intracellular free
      calcium induced by the TxA2 agonists I-BOP or U-46619 was significantly (P <
      0.005) greater in testosterone-treated cells compared with controls.
      Hydroxyflutamide (1 microM), an androgen-receptor antagonist, completely blocked
      the effect of testosterone (P < 0.01). Dihydrotestosterone, the active metabolite
      of testosterone, also increased Bmax in a concentration-dependent manner and was
      more potent than testosterone. The effect of testosterone to increase Bmax was
      significantly (P < 0.01) inhibited by coincubation with cycloheximide (0.1
      microgram/ml) or actinomycin D (10 ng/ml). These results indicate that androgenic
      steroids regulate the expression of functional TxA2/PGH2 receptors in HEL cells.
      These findings may have relevance to cardiovascular disease.

PMID- 8279550
TI  - Effects of physiological hyperinsulinemia on the intracellular metabolic
      partition of plasma glucose.
AB  - Methodology for assessing the glycolytic and oxidative fluxes from plasma
      glucose, by measuring 3H2O and 14CO2 rates of production during [3-3H]- and [U
      14C]glucose infusion, was tested in healthy subjects. In study 1, during
      staircase 3H2O infusion in six subjects, calculated rates of 3H2O appearance
      agreed closely with 3H2O infusion rates. In study 2, when [2-3H]glucose and
      NaH14CO3 were infused in four subjects in the basal state and during a 4-h
      euglycemic insulin (approximately 70 microU/ml) clamp, accurate estimates of the
      rates of [2-3H]glucose detritiation were obtained (94-97% of the expected
      values), and the recovery factor of NaH14CO3 did not change during
      hyperinsulinemia. In study 3, 11 subjects underwent a 4-h euglycemic insulin
      (approximately 70 microU/ml) clamp with [3-3H]- and [U-14C]glucose infusion and
      measurement of gaseous exchanges by indirect calorimetry to estimate the rates of
      total glycolysis, glycogen synthesis, glucose oxidation, nonoxidative glycolysis,
      hepatic glucose production, glucose recycling, and glucose conversion to fat.
      Hyperinsulinemia stimulated glycogen synthesis above baseline more than
      glycolysis [increment of 4.78 +/- 0.37 vs. 2.0 +/- 0.17 mg.min-1 x kg-1 of lean
      body mass (LBM), respectively, P < 0.01] and incompletely suppressed
      (approximately 87%) hepatic glucose production. The major component of
      nonoxidative glycolysis shifted from glucose recycling in the postabsorptive
      state (approximately 57% of nonoxidative glycolysis) to glucose conversion to fat
      during hyperinsulinemia (approximately 59% of nonoxidative glycolysis). Lipid
      oxidation during the insulin clamp was negatively correlated with both isotopic
      glucose oxidation (r = -0.822, P < 0.002) and glycolysis (r = -0.582, P < 0.07).
      In conclusion, in healthy subjects, glycogen synthesis plays a greater role than
      glycolysis and glucose oxidation in determining insulin-mediated glucose
      disposal. Part of insulin-mediated increase in glycolysis/oxidation might be
      secondary to the relief of the competition between fat and glucose for oxidation.

PMID- 8279551
TI  - Relationship between tumor necrosis factor-alpha and neutrophils in endotoxin
      induced liver injury.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and blood neutrophils (polymorphonuclear
      leukocytes; PMNs) have been implicated in the pathogenesis of endotoxin
      (lipopolysaccharide, LPS) hepatotoxicity. However, the mechanism by which these
      factors mediate liver injury during LPS exposure is uncertain. The objective of
      this study was to test the hypothesis that TNF-alpha contributes to LPS
      hepatotoxicity by an indirect, PMN-dependent mechanism. Pretreatment of rats with
      an antiserum to TNF-alpha afforded protection against liver injury 6 h after LPS
      exposure. Pretreatment with pentoxifylline (100 mg/kg i.v.), which attenuated the
      increase in circulating TNF-alpha concentration 1.5 h after administration of
      LPS, also afforded protection against liver injury. Neither antiserum to TNF
      alpha nor pentoxifylline affected hepatic PMN accumulation 1.5 h after LPS
      exposure. Depletion of circulating PMNs, which protects against LPS
      hepatotoxicity, enhanced circulating TNF-alpha concentration compared with
      control rats 1.5 h after LPS exposure. These results suggest that TNF-alpha
      contributes to liver injury after LPS exposure, but in the absence of circulating
      PMNs it is insufficient for full manifestation of liver injury. TNF-alpha
      apparently contributes to the pathogenesis of LPS-induced liver injury by an
      indirect, PMN-dependent mechanism.

PMID- 8279552
TI  - Effect of vagotomy on ornithine decarboxylase activity in rat duodenal mucosa.
AB  - The aim of this study was to determine whether the circadian rhythm of ornithine
      decarboxylase (ODC) activity in rat small intestine is controlled by factors
      other than luminal nutrients. ODC activity in duodenal and jejunal mucosa of rats
      fed ad libitum was measured at four time points (0500, 1100, 1700, 2300 h; light
      period: 0800-2000 h). ODC activity in the jejunum increased in the dark period,
      which is when rats normally eat. In contrast, ODC activity in the duodenum began
      to increase at 1700 h, which is when rats do not normally eat, as indicated by
      the recorded feeding pattern. The increase in ODC activity in the duodenum at
      1700 h, but not at other time points, was abolished by subdiaphragmatic vagotomy,
      whereas vagotomy had no effect on the feeding pattern of rats. Subdiaphragmatic
      vagotomy had no effect on ODC activity in the jejunum. ODC activity in the
      duodenum increased following glycoprivation of the central nervous system induced
      by infusion of 2-deoxyglucose into the third cerebroventricle. These results
      indicate that the increase in duodenal ODC activity at 1700 h is due to a signal
      from the upper brain structure through the vagal nerve and not to luminal
      nutrient factors.

PMID- 8279554
TI  - Pressure diuresis and natriuresis in cirrhotic rats.
AB  - Arterial hypotension in liver cirrhosis has been proposed as a major mechanism
      contributing to renal sodium and water retention. To evaluate kidney excretory
      responses at different levels of arterial pressure (AP), we have characterized
      the relationships between renal perfusion pressure (RPP) and sodium and water
      excretion in carbon tetrachloride cirrhotic rats. Experiments were performed in
      anesthetized control (n = 9) and cirrhotic rats with (Asc, n = 6) and without
      ascites (Cir, n = 6) by mechanically adjusting vascular resistance in animals
      with renal denervation and infused with main systemic hormones. Control and Cir
      animals showed similar glomerular filtration rates (GFR), renal blood flows,
      hematocrits (Hct), and plasma proteins (PP). However, Hct, PP, and GFR were
      significantly lower in the Asc rats. For the same level of RPP, both cirrhotic
      groups excreted significantly less water and sodium than controls. Then, the
      pressure diuresis and natriuresis relationships of the Cir animals were
      significantly depressed, but those of the Asc animals were more reduced than
      those of the Cir rats. These results indicate that the cirrhotic kidney is not
      able to normally increase the sodium and water excretion in response to changes
      in AP. Intrarenal mechanisms, and not mainly RPP, are likely mediators of the
      renal alterations of liver cirrhosis.

PMID- 8279553
TI  - Leukotriene B4 and C4 production in isolated rat gastric mucosal cells.
AB  - Dispersed rat gastric mucosal cells (F0) were separated into five fractions (F1
      F5) by counterflow elutriation, with F1 representing the smallest and F5 the
      largest cell diameters. In F0-F5, leukotriene B4 (LTB4) release in response to
      10(-5) M calcium ionophore A-23187 was 7.68 +/- 1.26, 51.6 +/- 10.8, 72.4 +/-
      10.4, 7.1 +/- 0.7, 5.7 +/- 0.6, and 11.6 +/- 3.4 pg.10(6) cells-1 x 30 min-1. In
      the identical fractions, sulfidopeptide release in response to A-23187 was 200.6
      +/- 20.5, 1,116.0 +/- 166.6, 1,309.4 +/- 163.2, 189.8 +/- 25.8, 108.0 +/- 18.0,
      and 158.4 +/- 54.0 pg.10(6) cells-1 x 30 min-1. High-pressure liquid
      chromatography verified the radioimmunologically determined LTB4 and identified
      LTC4 as the only sulfidopeptide LT released. LT release from F2 cells in response
      to A-23187 was time and dose dependent, reaching maximal stimulation at 10(-5) M
      A-23187. This response was blocked by the dual inhibitor of cyclooxygenase and
      lipoxygenases, BW755C (2 x 10(-5)-2 x 10(-4) M), by the selective 5-lipoxygenase
      inhibitor L-651,392 (10(-7)-10(-5) M), and by MK-886 (10(-9)-10(-7) M), which
      blocks translocation of 5-lipoxygenase. The postreceptor stimuli dibutyryl
      adenosine 3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoyl-phorbol-13
      acetate, and oleyl-acetyl-glycerol failed to induce LT release. However, 10(-4) M
      arachidonic acid increased basal LT release up to eightfold and increased A-23187
      stimulated LT release by an additional 30%.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279555
TI  - Neural mediation of cholera toxin-induced mucin secretion in the rat small
      intestine.
AB  - We examined the role of enteric nerves in cholera toxin (CT)-induced mucin
      secretion in proximal and distal regions of rat small intestine. Stimulation of
      intestinal loops with 120 micrograms (1.5 mumol) CT using an in vitro open-loop
      model resulted in an approximately four-fold increase in luminal mucin content
      over unstimulated controls in both regions of the gut. Prior treatment of loops
      with tetrodotoxin had no effect on the amount of mucin released in response to
      CT. However, permanent destruction of primary sensory afferent nerves by neonatal
      treatment of rats with capsaicin reduced the mucin response to CT to baseline
      levels in both regions. In normal animals, atropine resulted in approximately 40%
      inhibition of mucin secretion in both the proximal and distal small intestine.
      The atropine-sensitive secretory response appears to be a component of the
      capsaicin-sensitive response. These results suggest that choleraic mucin
      secretion is mediated primarily by a capsaicin-sensitive neurogenic pathway
      involving local activation of sensory nerves, which may then elicit mucin
      secretion through interaction with cholinergic nerves.

PMID- 8279556
TI  - Muscarinic cholinergic receptor density following small intestinal
      transplantation in rats.
AB  - After small intestinal transplantation, intestinal isografts can organize
      migrating myoelectric complexes, and we have shown that migrating myoelectric
      complex frequency in the fasted state was reduced compared with controls after
      transplantation of the distal 50% of small intestine. We hypothesized that
      changes in motor activity after transplantation were related to alteration of
      cholinergic nerve activity or receptor density. With use of standard
      microsurgical techniques, the distal 50% of small intestine was orthotopically
      transplanted in a Lewis-to-Lewis donor-recipient combination. Resection controls
      were prepared by resecting the proximal 50% of small intestine, and sham controls
      were prepared by performing a sham laparotomy. Two months after surgery, small
      intestine was harvested. Choline acetyltransferase activity among the three
      groups was similar, suggesting that intrinsic cholinergic nerves remained intact.
      There was a strong trend toward decreased acetylcholinesterase activity [analysis
      of variance (ANOVA), P = 0.16] after transplantation, consistent with loss of
      extrinsic vagal nerve fibers. There were no differences in histochemical
      distribution of acetylcholinesterase among these groups. Muscarinic receptor
      density, as determined by binding to [N-methyl-3H]scopolamine, was decreased
      after transplantation (ANOVA, P = 0.02). There was a trend toward decreased
      receptor density in animals with resected small intestine. Surgical interruption
      of intrinsic nerve pathways rather than ischemia or extrinsic denervation might
      be the mechanism for diminished receptor density after transplantation, and
      reduced small bowel motor activity may be related to decreased density of
      muscarinic cholinergic receptors.

PMID- 8279557
TI  - A novel in vitro technique to study extrinsic neural control of rabbit colonic
      muscle and epithelial function.
AB  - A novel in vitro technique capable of simultaneously measuring distal colonic
      epithelial potential difference and muscle contraction is described. Under basal
      conditions, oscillations in both muscle tone and potential difference were
      observed. Pelvic nerve stimulation was shown to evoke strong "duration"
      contractile responses in both the longitudinal and circular muscle layers.
      Additionally, tonic changes in potential difference extending beyond the train of
      stimuli were observed, suggesting for the first time that colonic ion transport
      may be influenced by the pelvic nerves. However, it was unclear whether these
      were direct effects or indirect actions resulting from muscle contractions
      causing mechanical stimulation of nerves of the submucosal plexus. Lumbar colonic
      nerve stimulation inhibited spontaneous contractile activity and reduced basal
      tone in both muscle layers. However, there was no consistent effect of
      sympathetic nerve stimulation on transepithelial potential difference. Each of
      the muscle and epithelial effects of sympathetic nerve stimulation was mimicked
      by exogenous norepinephrine. Based on these data, it is concluded that colonic
      function is strongly influenced by the extrinsic innervation. Furthermore,
      relatively long-term modulation of epithelial function can be achieved by short
      bursts of pelvic nerve activity.

PMID- 8279558
TI  - Vascular clearance and organ uptake of G- and F-actin in the rat.
AB  - This study comparatively evaluated the kinetics of removal and organ distribution
      of circulating G- and F-actin. Both F- and G-actin were cleared in two phases
      (fast component with a t1/2 of 3-5 min and a slow component with a t1/2 of
      hours). There was no effect of dose on either the fast- or slow-compartment
      clearance kinetics at the doses tested (5-100 micrograms/100 g body wt). However,
      at the same challenging dose of F- and G-actin, more F-actin was removed during
      the rapid phase. Although the time constants (Tfast) for F- and G-actin removal
      from the vasculature during the initial rapid phase were the same, during the
      slow phase the time constants (Tslow) for removal of F-actin were less (P <
      0.001) than that of G-actin. The fraction of F-actin removed during the rapid
      phase ranged from 33 to 63% and was significantly greater (P < 0.01) than the
      fraction of G-actin removed during this phase (10-33%). The liver was the main
      organ of localization, and autoradiographic studies of liver tissue demonstrated
      that G-actin monomers were removed by Kupffer cells, whereas F-actin was
      predominantly removed by hepatic sinusoidal endothelial cells. In vivo endotoxin
      activation of Kupffer cells enhanced the rate of G-actin removal and increased
      liver localization of G-actin but had no effect on F-actin removal. This further
      supports a role for Kupffer cells in the clearance of G-actin. These studies
      therefore demonstrate that F- and G-actin clearance mechanisms are different. G
      actin removal, presumably mediated by its binding to vitamin D binding protein,
      is accomplished by Kupffer cells, whereas F-actin removal at the same doses is
      due mainly to hepatic endothelial cell uptake.

PMID- 8279559
TI  - Interaction between signal transduction pathways contributing to gallbladder
      tonic contraction.
AB  - Muscle strips were used to study the mechanisms that generate cat gallbladder
      tone. Strontium substitution for calcium and the protein kinase C (PKC) inhibitor
      H-7 abolished the tone, whereas the calmodulin antagonist W-7 had no effect,
      suggesting that tone depends on intracellular calcium release and the PKC
      pathway. Basal levels of diacylglycerol (DAG) and inositol-1,4,5-trisphosphate
      (IP3) were higher in gallbladder muscle than in esophageal muscle, which does not
      maintain tone. These data suggest that IP3 might interact with DAG to activate
      PKC during tonic contraction. This interaction was demonstrated in single cells
      in which a low dose of IP3 potentiated DAG and the potentiation was blocked by H
      7. Furthermore, low doses of IP3 induced contraction, which was blocked by H-7
      and unaffected by the calmodulin antagonist CGS-9343B; high doses of IP3 were
      unaffected by H-7 but were blocked by CGS-9343B; DAG-induced contraction was
      blocked by activated calmodulin. We conclude that 1) the synergistic action of
      DAG and IP3-calcium release, which further activates PKC, might be responsible
      for gallbladder tone and 2) activated calmodulin appears to inhibit the effect of
      PKC.

PMID- 8279560
TI  - Regulation of capillary exchange capacity in postnatal swine intestine.
AB  - To determine whether intrinsic regulation of capillary exchange capacity is age
      dependent during early postnatal life, we measured the capillary filtration
      coefficient (Kf,c), an index of capillary exchange capacity, within isolated
      perfused intestine from 3- and 35-day-old swine at different arterial pressures.
      Kf,c was determined gravimetrically, by means of the flow-equilibration
      technique. During baseline perfusion at age-appropriate pressures, Kf,c averaged
      0.203 +/- 0.020 vs. 0.361 +/- 0.040 ml.min-1 x mmHg-1 x 100 g in 35- vs. 3-day
      old intestine. In older animals, a progressive rise in Kf,c was noted as arterial
      pressure was lowered: Kf,c increased 14, 35, and 98% above baseline when pressure
      was reduced 20, 40, and 60% below baseline, respectively. An inverse linear
      correlation between Kf,c and blood flow was demonstrated in this group. Kf,c also
      increased in 3-day-old intestine during progressive hypotension, but these
      changes were of less magnitude: Kf,c averaged 19, 17, and 23% above baseline when
      pressure was reduced 20, 40, and 60% below baseline, respectively. In contrast to
      the circumstance noted in older animals, the relationship between Kf,c and blood
      flow was not significant within 3-day-old intestine. Intraarterial infusion of 1
      microgram/min of isoproterenol, an agent known to increase capillary exchange
      capacity, caused Kf,c to increase 80% within 3-day-old intestine group. We
      conclude that Kf,c increases to a greater extent in 35- than 3-day-old swine
      intestine in response to arterial pressure reduction. However, intestine from
      younger animals is capable of increasing capillary exchange capacity in response
      to stimuli other than arterial hypotension, as evidenced by its response to
      isoproterenol.

PMID- 8279561
TI  - Topography of normal and high-amplitude esophageal peristalsis.
AB  - Topographic plots were created from esophageal manometric tracings in 12
      asymptomatic volunteers and 10 symptomatic patients with high-amplitude
      peristaltic contraction waves (nutcracker esophagus) to identify segmental
      contraction differences between the two groups. Median waves at each centimeter
      of esophageal length were spatially interconnected using a computerized gridding
      and plotting system, and a characteristic peristaltic contraction from the
      proximal esophageal body through the lower sphincter was constructed for each
      subject. Contour plots in the volunteers revealed three amplitude troughs
      dividing the peristaltic contraction into four sequential segments: the skeletal
      muscle body, the proximal and distal segments of the smooth muscle body, and the
      lower sphincter region. In nutcracker-esophagus patients, only the first and
      third troughs could be identified, since augmented contraction in the distal
      smooth muscle segment blurred separation of the smooth muscle body segments.
      Volume measurements under the topographic plots showed no significant intergroup
      differences in contraction of the skeletal muscle region or lower sphincter but
      modest increase in contraction of the proximal smooth muscle segment [1.7 times
      normal, 95% confidence interval (CI) 1.2-2.0; P = 0.002 comparing 2 groups] and
      marked increase in the distal smooth muscle segment (2.7 times normal, 95% CI 2.0
      3.3; P < 0.0001). These data indicate that normal peristalsis through the
      esophageal body and lower sphincter includes four separate contraction segments
      that can be distinguished with intraluminal manometry and the topographic
      analysis method. The nutcracker esophagus primarily affects the distal segment in
      the smooth muscle body.

PMID- 8279562
TI  - Intestinal lactase: maturational excess expression of mRNA over enzyme protein.
AB  - The mechanism of decline of intestinal lactase during mammalian development
      remains uncertain. Despite a major loss of catalytic activity, lactase mRNA
      appears to persist at detectable concentrations in adult rats. We quantified
      lactase activity, total lactase protein, and lactase mRNA in rats aged 7, 11, 15,
      18, 22, 30, and 60 days using the 7S ribosomal RNA as the developmental control.
      The active lactase fraction was 0.81 of total lactase for all age groups except
      60-day-old animals, in which it declined to 0.60 (P = 0.004), indicating that
      conversion of active lactase to inactive species contributed to the lower
      activity in the adult. Northern blots revealed a single discrete 6.8-kb message
      at all ages. Although lactase activity and immunoprotein decreased coordinately
      to a minimum by day 30 (20% of the 7-day value), lactase mRNA doubled to a
      maximum at day 22 and was maintained at 7-day concentrations even in 60-day
      adults. The lactase mRNA-to-protein ratio was low at 7 days (0.19) but more than
      doubled (0.50) by 22 days, achieved a fivefold increase (1.0) by 30 days, and
      persisted at 0.77 in adults. The relative excess of lactase message during
      maturation suggests that translational or post-translational events may be
      paramount in the developmental regulation of lactase gene expression.

PMID- 8279563
TI  - Relationship between muscarinic receptor occupancy and response in rat parotid
      acinar cells.
AB  - To determine whether spare muscarinic cholinergic receptors (mAChRs) exist in rat
      parotid acinar cells, we examined the effect of propylbenzilylcholine mustard
      (PBCM) on agonist (carbachol)-stimulated inositol trisphosphate (IP3) formation
      and on mAChR number, using l-[N-methyl-3H]scopolamine methyl chloride (NMS)
      binding assays. Treatment with PBCM (1, 3, 10, 30, 50 nM) for 15 min caused a 5,
      22, 60, 66, and 72% decrease, respectively, in maximal IP3 formation stimulated
      by carbachol as well as a large reduction in the potency of carbachol in
      eliciting this response. Using these data, equilibrium constants (Ka) for
      activation of the mAChRs by carbachol were calculated. These Ka values agreed
      well with Kd values of high-affinity mAChR binding sites determined from
      carbachol displacement of [3H]NMS binding in parotid acinar cells. Reduction in
      mAChR number after PBCM treatment was determined by Scatchard analysis of
      specific [3H]-NMS binding sites and compared with the expected reduction (q
      values) calculated from dose-response curves for carbachol-stimulated IP3
      formation before and after PBCM treatment. PBCM (1, 3, 10, 30 nM) decreased mAChR
      maximal binding in cells 47.5, 68.9, 82.4, and 85.3%, respectively, which did
      agree with the approximately 38, 70, 90, and 92% decrease in receptor number
      expected from the calculated q values. Data demonstrate that PBCM irreversibly
      inactivates mAChRs in rat parotid cells, and the decrease in receptor number,
      measured directly from [3H]NMS binding or calculated from receptor theory, is
      greater than that observed for stimulated IP3 production. These results suggest
      that a modest (30-40%) population of spare receptors exists for mAChR-mediated
      IP3 production in rat parotid glands.

PMID- 8279564
TI  - Effect of cyclooxygenase inhibition on macromolecular transport in rat gastric
      mucosa.
AB  - We have shown that the rat gastric mucosa takes up antigenically intact protein
      in vitro. The present study investigated the effect of two cyclooxygenase
      inhibitors, indomethacin and piroxicam, on gastric transport of BSA. Fasted rats
      were given indomethacin, piroxicam, or vehicle. After 30 min, the stomach was
      removed, stripped, and mounted in a Ussing chamber. Each side was bathed with
      Krebs buffer. Bovine serum albumin (BSA), 125I-labeled BSA (125I-BSA), and 51Cr
      labeled EDTA (51Cr-EDTA) were added to the mucosal fluid and equilibrated for 30
      min. Serosal fluids were sampled for two subsequent 30-min periods, and mean
      fluxes for immunologically intact BSA (enzyme-linked immunoabsorbent assay),
      total BSA (125I-BSA), and 51Cr-EDTA were calculated. Cyclooxygenase inhibition
      significantly (P < 0.01) reduced tissue prostaglandin E2 synthetic capacity
      (indomethacin, 97%; piroxicam, 92%) but did not cause either macroscopic or
      microscopic mucosal injury. Both inhibitors significantly (P < 0.05) decreased
      uptake of immunologically intact BSA (indomethacin, 91%; piroxicam, 81%) and 51Cr
      EDTA. In contrast, the movement of degraded BSA was not altered by indomethacin.
      These findings suggest that a selective pathway exists for the uptake of intact
      proteins in gastric mucosa and that the pathway is modulated by cyclooxygenase
      metabolites.

PMID- 8279565
TI  - Murine intestinal disaccharidases: identification of structural variants of
      sucrase-isomaltase complex.
AB  - This study was directed to determine the extent of variability in structure or
      expression of intestinal disaccharidase [gamma-glucoamylase (gamma-GA), sucrase
      isomaltase (SI), and lactase] between different strains of mice. Reduced levels
      of sucrase activity (approximately 20 U/g of protein) were observed in three
      strains of mice belonging to the CBA/Ca lineage. Four other strains of mice
      analyzed exhibited higher levels of sucrase activity (approximately 50 U/g of
      protein). Decreased levels of sucrase in CBA/Ca mice were not associated with
      decreased levels of activity associated with the isomaltase subunit or with
      decreased levels of SI mRNA expression. High-performance liquid chromatographic
      gel filtration, heat inactivation, and kinetic analysis indicated that the
      differences between strains in sucrase activity might be attributed to structural
      differences in the sucrase subunit of the SI complex, thus rendering it more
      susceptible to cleavage and inactivation. However, no differences in kinetic
      properties of the sucrase subunit were observed between strains. Murine gamma-GA
      was found to account for a greater proportion of maltase activity (approximately
      70%) than that observed in other species (i.e., approximately 20%). In addition,
      CBA/Ca mice were found to be deficient in intestinal maltase activity
      (approximately 60 U/g) compared with the other strains studied (approximately 300
      U/g).

PMID- 8279566
TI  - Characterization of intestinal gamma-glucoamylase deficiency in CBA/Ca mice.
AB  - In previous work, we found that CBA/Ca mice display only 20% of the maltase
      activity present in other mouse strains. In this study, we characterized more
      fully the maltase deficiency in CBA/Ca mice. Virtually all of the intestinal
      maltase activity of CBA/Ca mice was inactivated at 50 degrees C, indicating that
      it was due only to the sucrase-isomaltase complex. High-performance liquid
      chromatographic analysis revealed that CBA/Ca mice had undetectable maltase
      activity displaying the molecular mass characteristic of murine gamma
      glucoamylase (gamma-GA) (530 kDa). Gel electrophoretic analysis confirmed that
      CBA/Ca mice lacked maltase activity with molecular mass of 530 kDa corresponding
      to gamma-GA. Two-dimensional electrophoretic analysis revealed that the gamma-GA
      deficiency in CBA/Ca mice was due to the failure to synthesize the enzyme and not
      to the synthesis of an inactive protein. gamma-GA maltase activity could not be
      induced in CBA/Ca mice by a diet rich in starch, whereas the activity of other
      disaccharidases were readily increased. gamma-GA-deficient CBA/Ca mice appear to
      lack any gross metabolic abnormality resulting from this defect.

PMID- 8279567
TI  - Effects of vasoactive intestinal contractor on voltage-activated Ca2+ currents in
      feline parasympathetic neurons.
AB  - Intracellular current-clamp and single-electrode voltage-clamp techniques were
      used to study in vitro action potentials and the action of vasoactive intestinal
      contractor (VIC; 0.03-1 microM) on the high-voltage-activated Ca2+ currents (ICa)
      of neurons in feline colonic parasympathetic ganglia. In the current-clamp
      recording mode, action potential amplitude was depressed by cobalt (1 mM) and
      omega-conotoxin (300 nM) or in nominally Ca(2+)-free Krebs solutions. In the
      single-electrode voltage-clamp recording mode, the ICa was isolated by blocking
      the voltage-gated Na+ current with tetrodotoxin (1-3 microM) and by Krebs
      solutions containing a low Na+ concentration. The voltage-activated K+ currents
      were blocked by intracellular injection of cesium through a recording electrode
      filled with 2 M CsCl and external application of tetraethylammonium (30-50 mM)
      and barium (2 mM). The Ca(2+)-dependent Cl- current was blocked by replacement of
      Ca2+ (2 mM) with equimolar barium. Anomalous rectification was blocked by
      external application of 2 mM cesium. The ICa was evoked by depolarizing step
      commands more positive than -40 mV from holding potentials ranging between -80
      and -60 mV. ICa was depressed by cobalt (1 mM), cadmium (100 microM), and omega
      conotoxin (500 nM) but not by nifedipine (10 microM), nicardipine (10 microM),
      and verapamil (10 microM). BAY K 8644 (3-10 microM) also did not affect the ICa.
      VIC (0.1-1 microM), one of the endothelin (ET) isopeptides, caused an inward
      current followed by an outward current. The VIC-induced inward and outward
      currents were associated with an increase and decrease in membrane conductance,
      respectively. VIC also caused an initial depression followed by a long-lasting
      augmentation of the ICa. ET-1, ET-2, and ET-3 equally mimicked the action of VIC
      on both holding current and ICa. These data suggest that VIC activates a receptor
      operated channel and modulates the omega-conotoxin-sensitive voltage-activated
      Ca2+ channels through ETB receptor subtypes of neurons in feline colonic
      parasympathetic ganglia.

PMID- 8279568
TI  - Pancreatic polypeptide in dorsal vagal complex stimulates gastric acid secretion
      and motility in rats.
AB  - High concentrations of receptors for pancreatic polypeptide (PP), a pancreatic
      hormone, were recently discovered in the dorsomedial region of the dorsal vagal
      complex (DVC). We hypothesized that gastric acid secretion and motility,
      digestive functions strongly influenced by vagovagal reflexes organized within
      the DVC, would be affected by PP applied directly to this vagal sensorimotor
      integration area. After urethan-anesthetized rats were prepared for antral
      motility recording or titrometric analysis of gastric acid output, phosphate
      buffered saline or various doses of PP in phosphate-buffered saline were
      micropressure injected into the medial DVC. Injections of PP into the DVC
      produced significant, long-lasting, and dose-dependent increases in gastric acid
      secretion and antral motility. These gastric responses were blocked by bilateral
      cervical vagotomy and by atropine, suggesting that intramedullary PP stimulates
      vagal cholinergic pathways, resulting in enhanced gastric functions. Because PP
      is not synthesized within the central nervous system, these results point to a
      new mechanism whereby the digestive tract may modulate its own autonomic control:
      direct humoral action on vagovagal reflex circuits within the brain stem.

PMID- 8279569
TI  - Both low- and high-affinity CCK receptor states mediate trophic effects on rat
      pancreatic acinar cells.
AB  - Cholecystokinin (CCK) stimulates the growth of pancreatic acinar cells. However,
      the molecular mechanisms involved in this trophic action are unknown. CCK binds
      to both high- and low-affinity receptor states, and these two states appear to
      activate separate sets of intracellular messengers and have opposite effects on
      amylase release. JMV-180 is a CCK analogue that interacts in the rat with the
      high-affinity state as an agonist and the low-affinity state as an antagonist. In
      the current study, CCK octapeptide (CCK-8) and JMV-180 were tested for their
      ability to stimulate the growth of rat pancreatic acinar cells in primary
      culture. CCK-8 stimulated [3H]thymidine incorporation into DNA in a dose
      dependent manner. Effects were observed with 0.3 nM, and maximal increases were
      seen at 3 nM CCK-8 (442 +/- 53% of control, n = 5, P < 0.01). JMV-180 also
      stimulated DNA synthesis. Effects were noted with 10 nM, and a maximal increase
      of 267 +/- 82% (n = 4, P < 0.01) of control was stimulated by 100 nM JMV-180.
      These data with JMV-180 indicate that the high-affinity receptor state for CCK is
      capable of stimulating DNA synthesis. However, within the same experiment the
      effects of CCK were always significantly greater than those of JMV-180. To test
      whether CCK has an additional effect through interactions with the low-affinity
      state, the effects of a combination of JMV-180 with a maximal dose of CCK-8 were
      examined. JMV-180 inhibited the maximal effect of CCK-8 in a dose-dependent
      manner with a maximal inhibition occurring with 1 microM JMV-180. The effects of
      the combination of 3 nM CCK-8 and 1 microM JMV-180 were no greater than those of
      JMV-180 alone. Taken together these data indicate that CCK-mediated increases in
      DNA synthesis in rat pancreatic acinar cells in vitro occur by interactions with
      both high- and low-affinity receptor states.

PMID- 8279570
TI  - Lung morphometry: a new generation of tools and experiments for organ, tissue,
      cell, and molecular biology.
AB  - Today all structural information of the lung can be quantified and interpreted in
      the three-dimensional space of real-world biology. Remarkable achievements in the
      theory and practice of biological stereology are creating a new generation of
      data suitable for constructing structural hierarchies. Such hierarchies serve to
      organize and link biological data, thereby providing a framework on which to
      build new information systems. In this review, we describe the new tools of
      quantitative morphology and show how they can be used to design new experiments
      for lung research.

PMID- 8279571
TI  - Effect of airway inflammation on smooth muscle shortening and contractility in
      guinea pig trachealis.
AB  - We studied the effect of either 1) immunogenic inflammation caused by aerosolized
      ovalbumin or 2) neurogenic inflammation caused by aerosolized capsaicin in vivo
      on guinea pig tracheal smooth muscle (TSM) contractility in vitro. Force-velocity
      relationships were determined for nine epithelium-intact TSM strips from
      ovalbumin-sensitized (OAS) vs. seven sham-sensitized controls and TSM strips for
      seven animals treated with capsaicin aerosol (Cap-Aer) vs. eight sham controls.
      Muscle strips were tethered to an electromagnetic lever system, which allowed
      isotonic shortening when load clamps [from 0 to maximal isometric force (Po)]
      were applied at specific times after onset of contraction. Contractions were
      elicited by supramaximal electrical field stimulation (60 Hz, 10-s duration, 18
      V). Optimal length for each muscle was determined during equilibration. Maximal
      shortening velocity (Vmax) was increased in TSM from OAS (1.72 +/- 0.46 mm/s)
      compared with sham-sensitized animals (0.90 +/- 0.15 mm/s, P < 0.05); Vmax for
      TSM from Cap-Aer (0.88 +/- 0.11 mm/s) was not different from control TSM (1.13 +/
      0.08 mm/s, P = NS). Similarly, maximal shortening (delta max) was augmented in
      TSM from OAS (1.01 +/- 0.15 mm) compared with sham-sensitized animals (0.72 +/-
      0.14 mm, P < 0.05); delta max for TSM from Cap-Aer animals (0.65 +/- 0.11 mm) was
      not different from saline aerosol controls (0.71 +/- 0.15 mm, P = NS). We
      demonstrate Vmax and delta max are augmented in TSM after ovalbumin
      sensitization; in contrast, neurogenic inflammation caused by capsaicin has no
      effect on isolated TSM contractility in vitro. These data suggest that airway
      hyperresponsiveness in vivo that occurs in association with immunogenic or
      neurogenic inflammation may result from different effects of these types of
      inflammation on airway smooth muscle.

PMID- 8279572
TI  - Mechanisms of peroxynitrite-induced injury to pulmonary surfactants.
AB  - Activated alveolar macrophages secrete both nitric oxide and superoxide in the
      alveolar lining fluid which combine rapidly to form peroxynitrite, a potent
      oxidizing agent capable of damaging lipids and proteins in biological membranes.
      Peroxynitrite (1 mM) plus 100 microM Fe3+EDTA inhibited calf lung surfactant
      extract (CLSE) from reaching a minimum surface tension below 10 mN/m on dynamic
      compression. Peroxynitrite and its by-products reacted with the unsaturated lipid
      components of CLSE, as evidenced by the appearance of conjugated dienes and
      thiobarbituric acid products, and damaged all surfactant proteins. A mixture of
      the hydrophobic proteins [surfactant protein B (SP-B) and surfactant protein C
      (SP-C)] exposed to peroxynitrite became incapable of lowering phospholipid
      minimum surface tension on dynamic compression. Exposure of SP-A to peroxynitrite
      decreased its ability to cause lipid aggregation and to act synergistically with
      SP-B and SP-C in lowering surface tension of surfactant lipids. Western blot
      analysis of SP-A exposed to peroxynitrite was consistent with fragmentation and
      polymerization of the 28- to 36-kDa triplet band, and amino acid analysis
      revealed the presence of significant levels of 3-nitro-L-tyrosine. We conclude
      that peroxynitrite and its reactive intermediates inhibit pulmonary surfactant
      function by lipid peroxidation and damaging surfactant proteins.

PMID- 8279573
TI  - Dilator effect of endothelins in pulmonary circulation: changes associated with
      chronic hypoxia.
AB  - To investigate dilator effects of endothelins (ETs) on the pulmonary circulation
      and possible changes induced by chronic hypoxia, we examined vascular responses
      to ET-1 and ET-3 as well as ET binding to receptor subtypes ETA and ETB in the
      lungs from rats exposed to either room air (controls), hypoxia (10% O2) for 3 wk
      (3 WH), or 3 WH followed by recovery to room air (3 WH+R). In controls, both ETA
      and ETB receptor binding was present in smooth muscle of airways and vessels.
      Infusion of ET-1 or ET-3 (3-100 pM) to isolated perfused lungs preconstricted by
      U-46619 produced dose-dependent vasodilation with a greater potency of ET-3 (P <
      0.01). The vasodilator responses to ET-1 and ET-3 were potentiated by the
      cyclooxygenase blocker meclofenamate (3 x 10(-6) M) or by the thromboxane
      synthetase inhibitor R-68070. In meclofenamate-treated lungs, the vasodilator
      responses to ET-1 and ET-3 remained unaffected by the inhibitor of nitric oxide
      synthesis, NG-monomethyl-L-arginine (5 x 10(-4) M) or by the guanylate cyclase
      inhibitor, methylene blue (10(-4) M). Conversely, the K+ channel blockers
      glibenclamide (10(-4) M) and tetraethylammonium (10(-4) M) attenuated the
      vasodilator responses to both ET-1 and ET-3. The selective ETA receptor
      antagonist BQ-123 did not alter ET-induced vasodilation, whereas it attenuated ET
      induced vasoconstriction. Vasodilation to both ET-1 and ET-3 was abolished in
      lungs from 3 WH rats (P < 0.01) but was fully restored in lungs from 3 WH+R rats.
      Pulmonary vasodilation induced by the K+ channel opener pinacidil, which was
      suppressed by glibenclamide, did not differ between controls and 3 WH rat lungs.
      We found no change in ETA and ETB receptor binding from pulmonary vessels in H
      rat lungs compared with controls. In conclusion, endothelin-induced pulmonary
      vasodilation which may involve activation of K+ channels is abolished during
      chronic hypoxia. This abolition does not appear to be related to alterations in
      ET-receptor subtypes or to unresponsiveness of K+ channels in the pulmonary
      circulation.

PMID- 8279574
TI  - Secretion of surfactant protein A from rat type II pneumocytes.
AB  - Secretion of surfactant phosphatidylcholine has been extensively studied and
      there is evidence that it is a regulated process that can be influenced by a
      variety of physiological factors and pharmacological agents. In contrast,
      secretion of the major surfactant protein, surfactant protein A (SP-A), has been
      investigated to much lesser extent. It is not known whether SP-A secretion is
      constitutive or regulated and, if regulated, whether its regulation is similar to
      that of phosphatidylcholine. To address those questions we measured SP-A
      secretion in primary cultures of type II pneumocytes under conditions identical
      to those used to study phosphatidylcholine secretion. Freshly isolated cells from
      adult rats were cultured overnight, washed, and then incubated in fresh medium in
      the presence and absence of surfactant phospholipid secretagogues. As previously
      reported for phosphatidylcholine, SP-A secretion was linear with time for up to 4
      h. However, the rate of SP-A secretion, approximately 6% of total SP-A
      (cells+medium) released into the medium per hour, was more than sixfold greater
      than that of the lipid. Although freshly isolated cells contained 70% more SP-A
      than cells that were cultured overnight, the rate of SP-A secretion was not
      significantly different. Secretion of SP-A by freshly isolated or cultured type
      II cells was not increased by a combination of ATP, terbutaline, the adenosine A2
      receptor agonist 5'(N-ethylcarboxyamido)adenosine, 12-O-tetradecanoylphorbol-13
      acetate, and ionomycin at concentrations that optimally stimulated
      phosphatidylcholine secretion. We conclude that secretion of the major lipid and
      protein components of surfactant are independently regulated.

PMID- 8279575
TI  - Effect of hypoxia and norepinephrine on cytoplasmic free Ca2+ in pulmonary and
      cerebral arterial myocytes.
AB  - The fluorescent calcium indicator, fura 2, was used to test whether contraction
      of primary cultured smooth muscle cells (SMC) from small pulmonary arteries in
      response to hypoxia and the relaxation by large pulmonary and cerebral artery SMC
      were mediated by changes in cytoplasmic free Ca2+ (Ca2+c). Because SMC from large
      pulmonary and cerebral arteries contract to norepinephrine (NE), Ca2+c levels
      during NE exposure were measured to determine if they differed from those seen
      with hypoxia. Under hypoxic conditions, Ca2+c increased 64.1 +/- 11.1% above the
      normoxic baseline in small pulmonary artery SMC. In SMC from large pulmonary and
      cerebral arteries, Ca2+c decreased 25.2 +/- 9.20 and 28.1 +/- 5.80%. Ethylene
      glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and ryanodine
      attenuated the Ca2+c increase in the small pulmonary artery SMC. On exposure to
      NE, Ca2+c increased markedly in all three SMC types. EGTA and ryanodine treatment
      also attenuated NE-induced Ca2+c increases in all three SMC types. These results
      show that the three SMC types mobilize their available Ca2+ stores differently
      when exposed to hypoxia but similarly when exposed to NE. The data also suggest
      that a change in the Ca2+c concentration, rather than a change in the Ca2+
      sensitivity of the contractile apparatus, is involved in the response to hypoxia.

PMID- 8279576
TI  - Role of myosin light-chain phosphorylation in endothelial cell retraction.
AB  - Endothelial cells retract centripetally when they are exposed to histamine and
      when extracellular calcium is chelated. This centripetal retraction implies that
      a centripetal tension must be expressed in the cells. We asked whether
      phosphorylation of the light chain of myosin (MLC) was important for the
      retraction to occur, and, by inference, expression of the tension. In human
      umbilical vein endothelial (HUVE) cells and in porcine pulmonary artery
      endothelial (PPAE) cells tryptic peptide maps indicated that MLC was
      phosphorylated by myosin light-chain kinase (MLCK). Activity of MLCK is inhibited
      by ML-9, a kinase inhibitor with relative specificity for MLCK, and when MLCK is
      phosphorylated by the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent
      kinase. Pretreatment of HUVE cells or PPAE cells with ML-9 or forskolin
      aminophylline (to increase cell cAMP) reduced basal MLC phosphorylation and
      prevented an expected increase in MLC phosphorylation following exposure of HUVE
      cells to histamine. Pretreatment of HUVE cells with ML-9 or forskolin
      aminophylline prevented HUVE cell retraction (measured as an increase in
      permeability of a monolayer of HUVE cells) in response to histamine. Pretreatment
      of PPAE cells with ML-9 or forskolin-aminophylline prevented PPAE cell retraction
      in response to chelation of extracellular calcium. These data support the
      hypothesis that phosphorylation of MLC is an important component of endothelial
      cell retraction.

PMID- 8279577
TI  - Hydrogen peroxide stimulates sodium-potassium pump activity in cultured pulmonary
      arterial endothelial cells.
AB  - Oxidant injury to pulmonary vascular endothelium is an important factor in the
      pathogenesis of acute lung injury. Oxidant injury to other cell types has been
      reported to alter the function of Na-K-adenosinetriphophatase (ATPase) an enzyme
      important in maintenance of cellular ionic homeostasis and in transport of ions
      across biological membranes. We investigated the effect of H2O2 (0.001-10 mM) or
      xanthine (X) (15.2 micrograms/ml) plus xanthine oxidase (XO) (0.0153 U/ml) on the
      Na-K pump activity of cultured bovine pulmonary arterial endothelial cells
      (PAECs). We used a functional assay, using 86RbCl as a tracer for K+ and
      expressing Na-K pump activity as ouabain-inhibitable K+ uptake. Our results
      demonstrate that H2O2 and X/XO stimulate Na-K pump activity of bovine PAECs, an
      effect prevented by catalase. In addition, we assessed the affinity, number, and
      turnover of [3H]ouabain binding sites on intact endothelial monolayers and found
      that H2O2 increased affinity to [3H]ouabain, decreased the number of binding
      sites, and increased the rate of pump turnover. Influx of 22Na increased in
      response to a nonlytic concentration of H2O2. Cell injury, as assessed by 51Cr
      release, adherent cell number, and phase-microscopic morphology, was not observed
      after 30-min incubations with the lowest dose (1 mM) of H2O2 effective in
      stimulating Na-K pump activity, or after incubation with X/XO. Na-K pump
      inhibition by ouabain significantly increased the 51Cr release caused by H2O2 or
      by X/XO, suggesting that the increase in Na-K pump activity may be a compensatory
      response to the cellular alterations produced by H2O2. Incubation with H2O2
      decreased cell ATP content, an effect which was not prevented by coincubation
      with ouabain. In summary, these results show that H2O2 increases Na-K pump
      activity of PAECs, an effect mediated, at least in part, by increased
      intracellular [Na] and by an increased rate of pump turnover. It is possible that
      the increased pump activity may be an early marker of endothelial cell
      perturbation.

PMID- 8279578
TI  - Enhanced rate of H2O2 release from bovine pulmonary artery endothelial cells
      induced by TGF-beta 1.
AB  - We have previously reported that transforming growth factor-beta 1 (TGF-beta 1)
      produces a "prooxidant" effect on cultured bovine pulmonary artery endothelial
      cells (BPAEC) [S. K. Das and B. L. Fanburg. Am. J. Physiol. 261 (Lung Cell. Mol.
      Physiol. 5): L249-L254, 1991]. This effect was found to be associated with a
      lowering of total cellular GSH (A.C. White, S. K. Das, and B.L. Fanburg. Am. J.
      Respir. Cell Mol. Biol. 6: 364-368, 1992). In this study, we demonstrate a
      twofold increase in the rate of extracellular H2O2 release from BPAEC after a 72
      h exposure to TGF-beta 1 (2 ng/ml, added at times 0 and 48 h). Increasing and
      decreasing the levels of cellular GSH with diethylmaleate (DEM, 0.05 mM) and
      buthionine sulfoximine (BSO, 0.01 mM), respectively, did not affect the rate of
      TGF-beta 1-induced increase in H2O2 release when compared with the individual
      effects of these reagents on control cells. The addition of BSO (0.01 mM) to
      control cells failed to demonstrate an increase in the rate of H2O2 release,
      despite a more profound decrease in cellular GSH by these cells than detected in
      cells treated with TGF-beta 1 alone. Moreover, a single dose of TGF-beta 1 (2
      ng/ml) induced a 63-85% increase in the rate of H2O2 release within 16 h of
      exposure, well before the previously demonstrated lowering of cellular GSH. These
      results indicate that the increase in H2O2 production by TGF-beta 1-stimulated
      BPAEC is associated with, but does not appear to be the result of, a lowering of
      cellular GSH. This study further suggests that the TGF-beta 1-induced H2O2
      production occurs at a site inaccessible to detoxification by GSH.

PMID- 8279579
TI  - Pulmonary carbonic anhydrase IV: developmental regulation and cell-specific
      expression in the capillary endothelium.
AB  - To investigate the pulmonary expression of membrane-associated carbonic anhydrase
      (CA IV), the full-length rat lung CA IV cDNA was isolated and characterized. The
      1,205-bp cDNA was found to encode a 309-amino acid protein, including a 27-amino
      acid hydrophobic COOH-terminal extension, presumably cleaved prior to transfer of
      the protein to its glycosyl-phosphatidylinositol membrane anchor. The tissue
      specific pattern of CA IV gene expression was found to be distinct from that of
      other CAs, with highest expression in lung, colon, kidney, brain, and heart.
      Pulmonary CA IV expression was found to be developmentally regulated, with a
      marked postnatal increase in mRNA content and immunoreactive protein
      concentration. CA IV localized by immunohistochemistry to the luminal side of the
      alveolar capillary endothelium, but was absent from endothelium of larger
      pulmonary vessels. Selective expression of CA IV in the alveolar capillaries
      provides evidence for specialized differentiation of this endothelial cell
      subpopulation and places CA IV in a strategic location to participate in carbon
      dioxide exchange and local pH regulation.

PMID- 8279580
TI  - Effects of inhibition of catalase and superoxide dismutase activity on
      antioxidant enzyme mRNA levels.
AB  - We examined the effects of inhibition of Cu,Zn superoxide dismutase (Cu,Zn SOD)
      and catalase (Cat) activities on the steady-state mRNA levels of the three major
      antioxidant enzymes [Cu,Zn SOD, Cat, and glutathione peroxidase (GP)] in human
      umbilical vein endothelial cells under normoxia and hyperoxia. Inhibition of Cat
      activity by aminotriazole was not associated with alteration of the other
      antioxidant enzymes or with potentiation of cell injury. On the other hand,
      inhibition of Cu,Zn SOD activity by N-N'-diethyl-dithiocarbamate (DDC) was
      associated with an increase in Cu,Zn SOD mRNA level and a decrease in Cat and GP
      mRNA level. The combination of DDC and hyperoxia treatments was associated with
      an additive effect on Cu,Zn SOD message. We propose that these coordinate mRNA
      changes might be an adaptation to the oxidative environment. This proposal
      supports the concept that the intracellular O2 metabolites themselves could be
      the signals that trigger the antioxidant enzymes gene expression.

PMID- 8279581
TI  - Changing attitudes about using animals.

PMID- 8279583
TI  - A laboratory exercise in somesthesis that is expeditious, inexpensive, and
      suitable for large classes.
AB  - A teaching laboratory is described that demonstrates two principles of the
      somatosensory system: 1) the "spot-like" nature of skin sensitivity and 2)
      tactile acuity. This laboratory has been used for a large medical school class
      (140-160 students). One reason for the success of this laboratory is the ability
      to provide a sufficient number of stimulating apparatuses. The two-point
      discrimination device used to measure tactile acuity can be made easily and
      cheaply. In addition, two other demonstrations are described that are suitable
      for smaller classes or that students can do on their own. Although this lab was
      designed for medical students, the content makes it suitable for undergraduate or
      high school students.

PMID- 8279582
TI  - Bovine and porcine large intestine as model epithelia in a student lab course.
AB  - A short-circuit current experiment on epithelial ion transport is described that
      is suitable for student classes in human and animal physiology. Segments of late
      distal colon from either pig or cow are obtained from the slaughterhouse
      depending on the animals' daily schedule. Initial tissue preparation already in
      the slaughterhouse, cold storage, and proper choice of bath solutions are
      essential prerequisites for success. Students monitor spontaneous transepithelial
      voltage and short-circuit current (Isc) by use of manually operated voltage clamp
      units. Two main transport mechanisms are studied, electrogenic Na+ absorption and
      Cl- secretion. Electrogenic Na+ absorption is studied by measuring the Isc drop
      after amiloride. Then Cl- secretion is stimulated by theophylline and
      subsequently inhibited by furosemide. In some experiments K+ secretion can be
      detected by the blocking effect of mucosal Ba2+. Response of tissues from pig and
      cow is qualitatively similar but quantitatively different. The equipment is
      sturdy and inexpensive, can be provided by most departmental workshops, and has
      been tested for 3 yr in regular lab courses. Observations made during these
      experiments are closely related to clinical states, such as secretory diarrhea,
      cystic fibrosis, and hyperaldosteronism, as well as to the mechanisms of
      clinically used diuretics.

PMID- 8279585
TI  - A simple analogue of lung mechanics.
AB  - A model of the chest and lungs can be easily constructed from a bottle of water,
      a balloon, a syringe, a rubber stopper, glass and rubber tubing, and clamps. The
      model is a more exact analogue of the body than the classic apparatus of Hering
      in two respects: 1) the pleurae and intrapleural fluid are represented by water
      rather than air, and 2) the subatmospheric "intrapleural" pressure is created by
      the elasticity of the "lung" (balloon) rather than by a vacuum pump. With this
      model, students can readily see how the lung is inflated and deflated by
      movements of the "diaphragm and chest" (syringe plunger) and how intrapleural
      pressures change as this is accomplished.

PMID- 8279584
TI  - Integrated cardiovascular physiology: a laboratory exercise.
AB  - Examining the hemodynamic responses to exercise provides a unique opportunity to
      analyze and integrate cardiovascular physiology because more is learned about how
      a system operates when it is forced to perform than when it is idle. We designed
      a laboratory exercise that examines the cardiovascular responses to exercise in a
      sedentary individual, an athlete, an individual with quadriplegia, and an
      individual with heart transplantation. The special populations were chosen
      because of their unique limitations and adaptations, which directly influence
      cardiovascular function. Basic anatomic and physiological data about the special
      populations are provided, and the students are challenged to analyze and
      assimilate information from figures, answer questions, make calculations, and
      plot graphs. The answers to the questions are provided in the APPENDIX. This
      laboratory exercise should be attempted in a group to foster discussions and
      interactions. The laboratory does not require any equipment or software. This
      exercise should be attempted after the cardiovascular section of the physiology
      course so that the students can integrate and apply the information presented
      during the course.

PMID- 8279586
TI  - Simple, inexpensive suction electrode system for the student physiology
      laboratory.
AB  - A versatile, inexpensive, easily constructed suction electrode system is
      described that can be used for routine exercises by the student on, or for
      demonstrations of, the electrophysiology of frog sciatic nerve and gastrocnemius
      and sartorius muscles. A disposable plastic syringe and a disposable pipette with
      Ag-AgCl wire comprise the suction electrode. Six readily manipulable electrodes
      are installed in the walls of the Plexiglas preparation bath, and an arbitrary
      number of additional "free" electrodes can be placed where desired. An optional
      small chamber, formed from a disposable plastic culture dish and Gootch rubber
      tubing, provides for "barrier" recording within the larger chamber.
      Interpretations are given of the electrical responses of nerve and muscle in
      terms of longitudinal currents along the preparation within the suction electrode
      tubes.

PMID- 8279587
TI  - Physiology laboratory experience for high school students.
AB  - Recently, we were charged with providing a learning opportunity for high school
      students participating in the Upward Bound Regional Math and Science Program, a
      program designed to stimulate interest in mathematics and science for students
      from disadvantaged environments. Our challenge was to introduce students to the
      joys, excitement, and mystery of physiology and to stimulate their interest for
      future study. To this end, we developed a laboratory experience that examined
      basic physiological concepts in an animal model. This opportunity introduced
      students to how their bodies work and the importance of the use of animals in
      research. The students left the experience confident, motivated, and excited
      about learning.

PMID- 8279588
TI  - The life and death of laboratory teaching of medical physiology: a personal
      narrative. Part II.
AB  - Part II of this essay describes the author's participation in the laboratory
      course instituted by Eugene Landis at Harvard in 1943, a course that drew heavily
      on Thomas Lewis's example. He describes in detail his own methods of laboratory
      teaching at Utah and Michigan when, as department chair, he had the
      responsibility for organizing courses in physiology for medical students. In
      conclusion, the author laments the curtailment and eventual abolition of
      laboratory teaching in the 1970s that resulted from curriculum reform, student
      revolt, and faculty indifference.

PMID- 8279589
TI  - Roar of whispers.

PMID- 8279590
TI  - Active learning: a personal view.

PMID- 8279591
TI  - The call for change in breast cancer screening guidelines.

PMID- 8279592
TI  - Cancer screening among African-American women: their use of tests and social
      support.
AB  - This study examined associations between social ties (as measured by the Social
      Network Index), instrumental and emotional support, and the use of three female
      cancer screening tests: mammography, cervical smear, and clinical breast
      examination. Data were taken from a household survey of 670 African-American
      women living in northern California in 1986. In multiple logistic regression
      models, Berkman's index was associated with increased use of mammography but not
      with the use of cervical smear or clinical breast examination. Instrumental and
      emotional support measures were not significant. These results suggest that
      social networks may have a role in early cancer detection.

PMID- 8279593
TI  - Promoting mammography use through progressive interventions: is it effective?
AB  - This study evaluated interventions implemented with women in a health maintenance
      organization who had not utilized their annual free mammogram referral 45 days
      (step 2) and 95 days (step 3) after its mailing. The step 2 evaluation compared
      mammography utilization for women randomly assigned to receive a brief reminder
      letter or no reminder: 42% of the reminder group vs 28% of the control group
      obtained mammograms. The step 3 evaluation compared utilization for women
      randomly assigned to receive a second reminder, a letter suggesting a preventive
      office visit, or telephone counseling: 29% of those who received telephone
      counseling, 14% of those who received a letter, and 12% of those who received a
      second reminder obtained mammograms.

PMID- 8279594
TI  - The use of mammography vans by low-income women: the accuracy of self-reports.
AB  - The objective of this study was to determine the accuracy of self-reports of
      mammography use by low-income income women. Mammography van records were used to
      verify self-reports of mammography use in the past year by women aged 50 through
      75 years who had visited five community health centers (n = 237). Van records
      verified mammography use for 99% of these women (82% within the previous year and
      98% within the past 2 years). Forty percent of those with van records who
      reported both the month and year of the mammogram were accurate. Inaccurately
      reported dates were more frequently after (74%) rather than before (26%) the
      actual date. These findings indicate that self-reports of mammography use by low
      income women are generally reliable.

PMID- 8279595
TI  - Screening for childhood lead poisoning: a cost-minimization analysis.
AB  - Decision analysis was used to compare the costs of three screening strategies for
      childhood lead poisoning: (1) venipuncture; (2) capillary sample with
      venipuncture confirmation if the blood lead level is elevated; (3) stratification
      by risk, with venipuncture for high-risk children and capillary sample for low
      risk children. Under baseline conditions, the cost of screening by the
      venipuncture, stratification, and capillary strategies is $22, $25, and $27,
      respectively. Venipuncture remains the least expensive strategy unless the cost
      of venipuncture is more than three times that of capillary sampling. The annual
      cost of a national lead screening program that uses a single venipuncture sample
      would be $352 million. Initial screening with a capillary sample would cost $432
      million, 23% more than venipuncture.

PMID- 8279596
TI  - Who participates in cardiovascular disease risk factor screenings? Experience
      with a religious organization-based program.
AB  - Adult members who declined participation in cardiovascular disease risk factor
      screenings offered at religious organizations were randomly selected and asked to
      participate in screenings at their homes. Relationships between screening
      participation and sociodemographic, behavioral, and physiological measures were
      examined. Age, knowledge of cardiovascular disease risk factors, body mass index,
      current smoking status, previous report of elevated blood pressure, current
      diastolic blood pressure measurement, frequency of worship service attendance,
      and residential distance from the religious organization screening site were
      important predictors of screening response. Those with conspicuous risk factors
      appeared less likely to initially respond to religious organization site
      screening invitations.

PMID- 8279597
TI  - Is cardiopulmonary resuscitation training deleterious for family members of
      cardiac patients?
AB  - The purpose of the study was to determine the attitudes toward cardiopulmonary
      resuscitation (CPR) training and subsequent CPR use of 172 CPR-trained family
      members of cardiac patients. The majority (88.9%) reported positive attitudes.
      Only 14 (8.1%) reported feeling too responsible for their family member. One
      hundred and forty-one (81.9%) said that they would perform CPR if required to do
      so. Family members do not feel unduly burdened by learning CPR, and CPR training
      should be recommended to families of patients at risk for sudden cardiac death.

PMID- 8279598
TI  - Educating patients with limited literacy skills: the effectiveness of printed and
      videotaped materials about colon cancer.
AB  - We investigated whether printed or videotaped information is more effective in
      enhancing colon cancer knowledge. Subjects (n = 1100) were randomized into three
      groups: to receive a booklet, view a videotape, or receive no intervention.
      Subjects receiving the intervention showed increased knowledge compared with
      control subjects (booklet = 23% and videotape = 26% vs no intervention = 3%).
      Findings suggest that personalized educational materials are effective in
      enhancing colon cancer knowledge.

PMID- 8279599
TI  - Promoting participation in breast cancer screening.

PMID- 8279600
TI  - The occupational risk of hepatitis C infection among hospital employees.

PMID- 8279601
TI  - The social correlates of regional rates of abortion.

PMID- 8279602
TI  - Primary care and emergency department overcrowding. 1. Achieving proportionate
      representation in samples.

PMID- 8279603
TI  - Primary care and emergency department overcrowding. 2. Successful referrals to
      primary care clinics.

PMID- 8279604
TI  - Federal funding of primary vs specialized medical education.

PMID- 8279605
TI  - Adiposity and stroke among older adults of low socioeconomic status: the Chicago
      Stroke Study.
AB  - OBJECTIVES: The purpose of this study was to test the hypothesis that overall and
      truncal adiposity increase the risk of stroke independent of their association
      with cardiovascular disease risk factors and other preexisting illnesses.
      METHODS: Analyses were conducted of longitudinal data from a poor, biracial
      cohort of noninstitutionalized adults 65 to 74 years of age who participated in
      the Chicago Stroke Study from 1965 to 1970. RESULTS: Ponderal index (cm/kg1/3)
      and chest skinfold were significantly associated with systolic and diastolic
      blood pressure, serum cholesterol and triglycerides, plasma glucose, and smoking.
      Ponderal index was also associated with diabetes and risk of stroke. After
      potential confounders were controlled, the following variables showed significant
      independent associations with risk of stroke: Black race, female gender, and age
      70+; hypertensive heart disease; and diabetes. Neither adiposity variable was
      associated with risk of stroke in the presence of these powerful predictors.
      CONCLUSIONS: Control of hypertension and diabetes continues to be important among
      older adults. Since excess adiposity seems to influence risk of stroke through
      its association with these disorders and other cardiovascular disease risk
      factors, control of weight and fat remains an important concern as well.

PMID- 8279606
TI  - Estimating clinical morbidity due to ischemic heart disease and congestive heart
      failure: the future rise of heart failure.
AB  - OBJECTIVES: Many developed countries have seen declining mortality rates for
      heart disease, together with an alleged decline in incidence and a seemingly
      paradoxical increase in health care demands. This paper presents a model for
      forecasting the plausible evolution of heart disease morbidity. METHODS: The
      simulation model combines data from different sources. It generates acute
      coronary event and mortality rates from published data on incidences,
      recurrences, and lethalities of different heart disease conditions and
      interventions. Forecasts are based on plausible scenarios for declining incidence
      and increasing survival. RESULTS: Mortality is postponed more than incidence.
      Prevalence rates of morbidity will decrease among the young and middle-aged but
      increase among the elderly. As the milder disease states act as risk factors for
      the more severe states, effects will culminate in the most severe disease states
      with a disproportionate increase in older people. CONCLUSIONS: Increasing health
      care needs in the face of declining mortality rates are no contradiction, but
      reflect a tradeoff of mortality for morbidity. The aging of the population will
      accentuate this morbidity increase.

PMID- 8279607
TI  - Self-reported physical activity in a rural county: a New York county health
      census.
AB  - OBJECTIVES: Few studies have described physical activity in rural populations.
      This study describes the frequency, types, and correlates of physical activity in
      29,304 free-living adults in a rural county in New York State. METHODS: Self
      reported responses about regular physical activity (maintained long enough to
      work up a sweat) were analyzed from a private household census of Otsego County
      with an 86.6% response rate. RESULTS: This survey categorized 46.2% of county
      residents as sedentary. Walking, the most frequent choice of activity (62% of the
      women, 36% of the men), increased in frequency with age of respondents whereas
      cycling, jogging, aerobics, team sports, and swimming (listed in rank order of
      frequency) generally tended to decrease in frequency with age. Farmers
      demonstrated an increased amount of "sweat activity" compared with persons in
      most other occupations. CONCLUSIONS: This descriptive study of physical activity
      in a rural county shows that sedentary lifestyle is of high prevalence. The high
      frequency of walking and the gender differences in both the levels and choice of
      activity suggest that further research and public policy recommendations focus on
      these issues.

PMID- 8279608
TI  - Car mass and fatality risk: has the relationship changed?
AB  - OBJECTIVES: The finding that the relative safety disadvantage of small compared
      with large cars is less for post-1980 cars than for pre-1980 cars has stimulated
      speculation that increasing fuel economy standards would increase fatalities less
      than previously expected. Fatal crashes between two cars of similar model year
      were examined to see whether this would be the case. METHODS: Driver fatality
      risk in relation to car mass was examined with Fatal Accident Reporting System
      data for crashes between two cars of a specific model year. RESULTS: The relative
      risk for driver fatality in the lighter car compared with the other driver's risk
      in a car 50% heavier was as follows: for 1966 through 1979 cars, the risk was
      between 3.7 and 5.1; for 1984 cars, 2.6; and for 1990 cars, 4.1. CONCLUSIONS: The
      results suggest that the lesser mass effect observed for mid-1980s cars occurred
      because improved crashworthiness features appeared in small cars earlier than in
      large cars. As all cars are redesigned, the relationship between risk and mass
      can be expected to approach that observed earlier in pre-1980 cars. If so, future
      fatality increases from fuel economy increases will be greater than estimated on
      the basis of mid-1980 data.

PMID- 8279609
TI  - Cesarean section and operative vaginal delivery in low-risk primiparous women,
      Western Australia.
AB  - OBJECTIVES: A major component of the increasing trend in cesarean sections in
      Western Australia is the rise in emergency cesarean sections in primiparous
      women. The aim of this study was to identify independent risk factors
      (particularly those known early in pregnancy) associated with operative delivery
      in low-risk primiparous women. METHODS: Retrospective multivariate logistic
      regression analyses of antenatal and perinatal data were conducted for all low
      risk primiparous women entering labor spontaneously and giving birth in Western
      Australia in 1987 (n = 3641). RESULTS: Of the subjects, 58% had a spontaneous
      vaginal delivery, 8% had an emergency cesarean section, and 34% had an operative
      vaginal delivery. The significant independent risk factors for emergency cesarean
      section were older maternal age, shorter maternal height, heavier infant
      birthweight, and long labor. The risk factors for operative vaginal delivery were
      older maternal age, shorter maternal height, heavier infant birthweight, epidural
      anesthesia, labor/delivery complications, male infant, private patient status,
      and being married. CONCLUSIONS: This multivariate analysis confirms known risk
      factors for operative delivery in low-risk primiparous women and suggests that it
      may be possible to predict the likelihood of operative delivery for an individual
      woman by using knowledge of maternal age and height and assessment of infant
      birthweight.

PMID- 8279610
TI  - Physicians' recommendations for mammography: do tailored messages make a
      difference?
AB  - OBJECTIVES: Message tailoring, based on individual needs and circumstances, is
      commonly used to enhance face-to-face patient counseling. Only recently has
      individual tailoring become feasible for printed messages. This study sought to
      determine whether printed tailored recommendations addressing women's specific
      screening and risk status and perceptions about breast cancer and mammography are
      more effective than standardized printed recommendations. METHODS: Computer
      assisted telephone interviews were conducted with 435 women, aged 40 to 65 years,
      who had visited family practice groups within the previous 2 years. Subjects were
      randomly allocated to receive individually tailored or standardized mammography
      recommendation letters mailed from physicians to patients' homes. Follow-up
      interviews were conducted 8 months later. RESULTS: Tailored letter recipients
      were more likely to remember and to have read more of their letters than
      standardized version recipients. After controlling for baseline status, tailored
      letter receipt was associated with more favorable follow-up mammography status
      for women with incomes below $26,000 and for Black women. CONCLUSIONS: Tailored
      messages are a more effective medium for physicians' mammography recommendations;
      tailoring may be especially important for women of low socioeconomic status.

PMID- 8279611
TI  - Mammography screening: how important is cost as a barrier to use?
AB  - OBJECTIVES: Recent legislation will improve insurance coverage for screening
      mammography and effectively lower its cost to many women. Although cost has been
      cited as a barrier to use, evidence of the magnitude of its effect on use is
      limited. METHODS: Mammography use in the past 2 years among women aged 50 to 75
      residing in four suburban or rural counties in Washington State was estimated
      from 1989 survey data. Logistic regression analysis was used to estimate the odds
      ratio of mammography use as a function of economic and other variables. Within a
      residential area, averages were used to measure the market price of mammography
      and the time cost to obtain a mammogram. RESULTS: Use was lower among women who
      faced a higher net price or who preferred to obtain a mammogram during weekend or
      evening hours and higher among women with higher incomes. Visiting no doctor
      regularly and smoking were predictors of failure to use mammography. CONCLUSION:
      The effects of economic variables on mammography use are important and stable
      across subsets of the population, but they are modest in size.

PMID- 8279612
TI  - Using census and mortality data to target small areas for breast, colorectal, and
      cervical cancer screening.
AB  - OBJECTIVES: The goal of this study was to develop and validate quantitative
      models for estimating cancer incidence in small areas. METHODS: The outcome for
      each cancer site was the incidence of disease that had reached a late stage at
      the time of diagnosis. Two sets of predictors were used: (1) census-based
      demographic variables and (2) census-based demographic variables together with
      the cancer-specific mortality rate. RESULTS: The best models accounted for a
      substantial percentage of between area variability in late-stage rates for cancer
      of the breast (46%), cervix (61%), and colon/rectum (58%). A validation procedure
      indicated that correct identification of small areas with high rates of late
      stage disease was two to three times more likely when model-based estimates were
      used than when areas were selected at random. CONCLUSIONS: Additional testing is
      needed to establish the generality of the geographic targeting methodology
      developed in this paper. However, there are strong indications that small-area
      estimation models will be useful in many regions where planners wish to target
      cancer screening programs on a geographic basis.

PMID- 8279613
TI  - Changes in the use of screening mammography: evidence from the 1987 and 1990
      National Health Interview Surveys.
AB  - OBJECTIVES: Mammography rates reported by women in the National Health Interview
      Surveys of 1990 and 1987 are examined. Why this screening modality is not more
      frequently used is explored. METHODS: Data from the 1987 and 1990 National Health
      Interview Surveys, conducted by the National Center for Health Statistics, are
      cross-tabulated and compared. RESULTS: In 1987, approximately 17% of women over
      40 years of age reported having had a screening mammogram in the previous year.
      In 1990, the rate doubled. Race declined in importance; income and education
      remained strong, positive predictors of screening. CONCLUSIONS: Despite this
      dramatic increase, two thirds of women are not having screening mammograms. Use
      was not higher primarily because women did not realize that screening mammography
      tests for breast cancer in asymptomatic women. Primary care physicians are the
      main source of health education for screening mammography. The data suggest that
      public health programs to promote screening mammography should especially target
      primary care physicians and women with low incomes and education. Likewise,
      health care providers should ensure that their patients are referred to
      facilities that deliver high-quality mammography at low cost to make the
      procedure more accessible.

PMID- 8279614
TI  - The next generation: poor compliance with risk factor guidelines in the children
      of parents with premature coronary heart disease.
AB  - OBJECTIVES: The offspring of individuals with premature coronary heart disease
      are themselves at increased risk for myocardial infarction before the age of 55.
      Consensus panels have recommended that all such offspring undergo an evaluation
      of cardiovascular risk, including cholesterol testing. METHODS: To examine self
      reported rates of cardiovascular risk factor assessment in this population, we
      conducted a telephone survey of 318 Canadian adults with premature coronary heart
      disease and of one offspring from 298 (94%) of the 318 families. RESULTS: The
      median age of the offspring was 20 years (range 2 to 39 y). Among the 219 late
      adolescent and young adult offspring, only 97 (44%) reported having had a blood
      cholesterol measurement during the preceding 3 years. Thirty-seven percent
      reported being current smokers, 31% were overweight, and 30% exercised fewer than
      three times per week. Men were less likely than women to report having had their
      blood pressure measured in the preceding year (57% vs 80%). CONCLUSION: These low
      rates of cardiac risk factor assessment families of patients with premature
      coronary heart disease represent missed opportunities for primary prevention.
      More effective strategies to prevent atherosclerosis in this population are
      needed.

PMID- 8279615
TI  - "Eat for Health": a supermarket intervention for nutrition and cancer risk
      reduction.
AB  - OBJECTIVES: The results of an evaluation of "Eat for Health," a supermarket
      nutrition intervention, are presented. The study tested whether such a program
      could be successfully carried out and whether it could effect changes in
      knowledge, attitudes, and food purchasing behavior in line with nutrition and
      cancer risk reduction guidelines. METHODS: The evaluation consisted of an in
      store monitoring element, an in-store and telephone consumer survey, and an
      analysis of sales data on selected foods. A matched-pair design, using a total of
      40 stores in the intervention and comparison groups, was used. RESULTS: The
      intervention was successfully implemented and had limited success in changing
      some food purchasing behaviors. There appeared to be no effect on knowledge and
      attitudes except for increased awareness of a link between diet and cancer and of
      the program itself. CONCLUSIONS: Despite the intervention's success, limitations
      of the consumer survey and sales data analyses and the continuing diffusion of
      nutrition messages throughout society make it difficult to specify the impact of
      this program on consumer nutrition knowledge and behaviors.

PMID- 8279616
TI  - A workplace intervention for increasing outdoor workers' use of solar protection.
AB  - OBJECTIVES: Outdoor workers are at high risk of developing skin cancer. Primary
      prevention in this group can potentially reduce the incidence of skin cancer, and
      also potentiates the spontaneous remission of existing solar keratoses. A
      randomized controlled trial was conducted to evaluate a solar protection
      intervention targeting outdoor workers. METHODS: Outdoor workers were randomly
      allocated to an intervention (n = 65) or control group (n = 77). The intervention
      group received individual skin screening by a dermatologist and participated in
      an education session. Pre- and posttest outcome measures included solar
      protection behavior (assessed using a validated diary), knowledge, and attitudes.
      RESULTS: There was a significant increase (16%) in the percentage of outdoor
      workers who were using a high level of solar protection at posttest compared to
      pretest in the intervention group, but there was no change in the control group.
      Although both groups improved in their knowledge score, the intervention group
      showed a significantly greater improvement at posttest. No changes in attitudes
      were detected. CONCLUSIONS: The findings suggest that changes in solar protection
      are achievable with outdoor workers.

PMID- 8279617
TI  - Cancer prevention: accomplishments and prospects.

PMID- 8279618
TI  - Racial disparities in reported prenatal care advice from health care providers.
AB  - OBJECTIVES: The relationship between certain maternal behaviors and adverse
      pregnancy outcomes has been well documented. One method to alter these behaviors
      is through the advice of women's health care providers. Advice from providers may
      be particularly important in minority populations, who have higher rates of
      infant mortality and prematurity. This study examines racial disparities
      according to women's self-report of advice received from health care providers
      during pregnancy in four areas: tobacco use, alcohol consumption, drug use, and
      breast-feeding. METHODS: Health care providers' advice to 8310 White non-Hispanic
      and Black women was obtained from the National Maternal and Infant Health Survey.
      RESULTS: After controlling for sociodemographic, utilization, and medical
      factors, Black women were more likely to report not receiving advice from their
      prenatal care providers about smoking cessation and alcohol use. The difference
      between Blacks and Whites also approached significance for breast-feeding. No
      overall difference was noted in advice regarding cessation of drug use, although
      there was a significant interaction between race and marital status. CONCLUSIONS:
      These data suggest that Black women may be at greater risk for not receiving
      information that could reduce their chances of having an adverse pregnancy
      outcome.

PMID- 8279620
TI  - Correlates of high-density lipoprotein cholesterol in black and white women.
AB  - The relationships of high-density lipoprotein (HDL) cholesterol with body
      composition, leisure-time physical activity, cigarette smoking, and education
      were examined in a community-based sample of 480 Black and 1337 White women.
      Univariate and multivariate analyses indicated inverse associations of HDL with
      body mass index and waist-to-hip ratio in both groups, and with cigarette smoking
      and low educational attainment among White women only. Since correlates of HDL
      cholesterol differ for Black and White women, further investigation of the
      differences in these correlates is warranted.

PMID- 8279619
TI  - Infant feeding policies in maternity wards and their effect on breast-feeding
      success: an analytical overview.
AB  - OBJECTIVES: The purpose of this review is to examine the plausibility of a causal
      relationship between maternity ward practices and lactation success. METHODS:
      Studies were located with MEDLINE, from our personal files, and by contacting
      researchers working in this field. Of the 65 studies originally reviewed, 18 met
      our inclusion criteria (i.e., hospital-based intervention, experimental design
      with randomization procedures, or quasi-experimental design with adequate
      documentation). RESULTS: Meta-analysis indicated that commercial discharge packs
      had an adverse effect on lactation performance. The impact of early mother-infant
      contact on lactation success was unclear. Rooming-in and breast-feeding guidance
      in a rooming-in context had a beneficial impact on breast-feeding among
      primiparae. Breast-feeding on demand was positively associated with lactation
      success. In-hospital formula supplementation of 48 mL per day was not associated
      with poor breast-feeding performance. CONCLUSIONS: Hospital-based breast-feeding
      interventions can have a beneficial effect on lactation success, particularly
      among primiparous women.

PMID- 8279621
TI  - Sclerosing peritonitis associated with luteinized thecomas of the ovary. A
      clinicopathological analysis of six cases.
AB  - Six cases of a distinctive ovarian lesion associated with sclerosing peritonitis
      were found in patients 13 to 76 years of age. Five patients presented with
      abdominal swelling; on examination, three were found to have unilateral or
      bilateral pelvic masses, one had ascites and evidence of small bowel obstruction,
      and one had ascites alone. The sixth patient presented with small bowel
      obstruction. At operation, 1 to 9 L of ascitic fluid were found in five patients.
      Five patients with bilateral ovarian enlargement underwent bilateral oophorectomy
      or, in one case, bilateral ovarian wedge resection. The sixth patient had
      unilateral ovarian enlargement treated by unilateral oophorectomy. All had
      fibrotic thickening of the peritoneum, most prominently involving the omentum and
      small bowel, four at initial operation and two at a second operation performed
      shortly thereafter. One or more episodes of small bowel obstruction subsequently
      occurred in three of the five patients with follow-up. One woman died of
      pulmonary embolism 2 months after her initial operation; four were alive without
      clinical evidence of disease 8 months to 6 years postoperatively. Gross
      examination revealed unilateral (one case) or bilateral (two cases),
      predominantly solid ovarian tumors 12 to 31 cm in maximum dimension in three
      cases and slight enlargement and nodularity of both ovaries in the other three
      cases. Microscopic examination of the ovaries revealed a cellular proliferation
      of spindle cells with focal differentiation into nests of luteinized or partially
      luteinized cells; one case also had occasional foci of sex cord elements. The
      process was confined to the ovarian cortex in the three cases with slight ovarian
      enlargement. Residual ovarian follicles were entrapped by the proliferation in
      three cases, but were prominent in only one of them. Additional features included
      brisk mitotic activity, predominantly in the spindle cells, in three cases, and
      striking edema in the three cases with significant ovarian enlargement. The
      ovarian lesions were interpreted as luteinized thecomas, although a closely
      related hyperplasia with luteinization, instead of early neoplasia, cannot be
      excluded in the three cases with only slight ovarian enlargement (and in one,
      prominent entrapment of follicles). The peritoneal process consisted of a
      variably cellular proliferation of fibroblasts and myofibroblasts separated by
      collagen, fibrin, and occasional chronic inflammatory cells. These cases and two
      similar cases from the literature suggest a unique association between some
      luteinized thecomas (or a closely related proliferative lesion of the ovary) and
      sclerosing peritonitis, although the relation between the ovarian and peritoneal
      processes is presently enigmatic.

PMID- 8279622
TI  - Mucinous meningioma. Report of an unusual variant of meningioma that may mimic
      metastatic mucin-producing carcinoma.
AB  - An unusual variant of meningioma is described that was characterized by small
      clusters and strands of meningothelial cells surrounded by abundant mucinous
      stroma. The unusual appearance of the lesion prompted an initial diagnosis of
      metastatic mucin-secreting carcinoma (so-called colloid carcinoma) resulting in
      extensive clinical evaluation in search for a primary. Histochemical studies
      showed the mucinous material to be composed of strongly sulfated acid
      mucopolysaccharides rich in hyaluronic acid. Immunohistochemical studies showed
      strong membrane staining of the tumor cells with epithelial membrane antigen and
      positive cytoplasmic staining with vimentin antibodies. Ultrastructural
      examination revealed the characteristic features of meningothelial cells (i.e.,
      abundant long, interdigitating cytoplasmic processes joined by well-developed
      cell junctions) but failed to demonstrate secretory activity within the
      neoplastic cells. The prominent mucinous stroma in this case most probably
      represents a nonspecific reaction of stromal cells to an undetermined stimulus.
      Mucinous meningioma should be added to the list of morphologic variants of
      meningioma and should be considered in the differential diagnosis of mucinous
      lesions in intracranial locations.

PMID- 8279623
TI  - Cerebral metastasis of an atrial myxoma mimicking an epithelioid
      hemangioendothelioma.
AB  - A 60-year-old woman presenting with a 15-month history of Jacksonian seizures was
      found on computed tomography (CT) scan to have an enhancing subcortical lesion
      high in the left anterior parietal lobe. The excised tumor had light microscopic
      features similar to those of an epithelioid hemangioendothelioma, and
      immunohistochemical stains confirmed its vascular nature. At surgery, the patient
      had no clinical or radiological (including CT body scan) evidence of any other
      lesion. However, 22 months after symptoms first appeared, she presented with
      dyspnea and bilateral pleural effusions, and a left atrial myxoma was detected
      echocardiographically. The histologic features of the resected myxoma were
      identical to those of the previously excised cerebral lesion, and it became
      apparent that the intracranial tumor was a metastasis of the atrial myxoma. This
      case illustrates that before a diagnosis of visceral epithelioid
      hemangioendothelioma is rendered, the possibility of metastatic occult cardiac
      myxoma should be considered. Echocardiography is warranted for such patients.

PMID- 8279624
TI  - A requiem to Hodgkin's disease?

PMID- 8279625
TI  - Fibrosarcoma in infants and children. Application of new techniques.
AB  - Fibrosarcomas occurring in infants and young children are intriguing tumors.
      Although biologically more benign than their counterparts occurring in old
      patients, they are histologically similar. Microscopically, they fit in one end
      of a spectrum of fibrous proliferations occurring in the pediatric population.
      Prompted by recent karyotypic reports of nonrandom gains of chromosomes 8, 11,
      17, and 20 in infantile fibrosarcomas, we retrospectively analyzed 12 infantile
      fibrosarcomas utilizing fluorescence in-situ hybridization (FISH) with chromosome
      8-, 11-, 17-, and 20-specific probes. Parallel studies were performed on
      fibrosarcomas occurring in older children and young adults and also on cellular
      fibromatoses, myofibromatoses, and fibromatoses. Gains of chromosomes 8, 11, 17,
      and 20 (in various combinations) were observed in 11 of 12 fibrosarcomas
      occurring in infants < 2 years of age. Extra copies of chromosomes 17 and 20 were
      observed in a fibrosarcoma occurring in a 5-year-old child but no abnormalities
      were detected by FISH in four additional fibrosarcomas occurring in patients aged
      6-17 years. One of three cellular fibromatoses was characterized by extra copies
      of chromosome 8, 11, 17, and 20. Similar findings were not observed in any of the
      noncellular fibromatoses or in myofibromatoses.

PMID- 8279626
TI  - Salivary gland anlage tumor ("congenital pleomorphic adenoma"). A
      clinicopathologic, immunohistochemical and ultrastructural study of nine cases.
AB  - Salivary gland anlage tumor (SGAT) is a polypoid lesion of the nasopharynx that
      presents with respiratory distress at birth or within the first few days or weeks
      of life. Among our nine cases, there was a male predilection (7M:2F). All tumors
      were in the midline and attached to the posterior pharyngeal wall by a delicate
      pedicle. The largest tumor measured 3 cm. A biphasic histologic pattern of
      squamous nests and duct-like structures at the periphery blended into solid,
      predominantly mesenchymal-appearing nodules centrally. The surrounding submucosal
      mantle of epithelial structures was consistently immunoreactive for cytokeratin
      and epithelial membrane antigen, whereas the stromal-like cells of the central
      nodules showed variable immunopositivity for cytokeratin, vimentin, and muscle
      specific actin. Both components were equally reactive for salivary gland amylase.
      Ultrastructurally, some of the stromal-like cells had features of myoepithelial
      cells. The histologic and architectural features of SGAT are similar in some
      respects to the developing salivary gland. It is proposed that the SGAT is a
      probable hamartoma of minor salivary gland derivation whose origin in the
      nasopharynx is potentially life-threatening in an infant.

PMID- 8279627
TI  - Floral variant of follicular lymphoma. Immunological and molecular studies
      support a neoplastic process.
AB  - In recent reports of the so-called "floral variant" of follicular lymphoma, an
      unusual variant of follicular lymphoma mimicking progressive transformation of
      germinal centers, questions have been raised regarding whether this process
      represents a malignant lymphoma. We studied 19 examples of the floral variant of
      follicular lymphoma and report our light microscopic, immunohistochemical, and
      molecular diagnostic findings. Morphologic changes consisted of effacement of
      normal lymph node architecture by follicles composed of atypical lymphocytes. The
      follicles were surrounded by prominent mantle zones that invaginated irregularly
      into the follicle centers, often imparting a "floral" appearance. Sufficient
      material was available for immunophenotypic or genotypic studies in 15 biopsies.
      Twelve of 15 cases studied by immunohistochemistry demonstrated phenotypes
      supporting a diagnosis of lymphoma. Five demonstrated light-chain restriction;
      one was an immunoglobulin-negative B-cell neoplasm; and six, in which only
      formalin-fixed, paraffin-embedded tissue was available, demonstrated
      overexpression of the bcl-2 protein. Southern blot analysis revealed evidence of
      clonal immunoglobulin heavy-chain gene rearrangement in all five cases tested.
      Overall, 12 of the 15 biopsies studied with these techniques showed immunologic
      or genotypic support for malignant lymphoma. The results of this study
      demonstrate that the floral variant of follicular lymphoma does indeed represent
      a malignant lymphoma.

PMID- 8279628
TI  - Epstein-Barr virus is infrequently identified in non-Hodgkin's lymphomas
      associated with Hodgkin's disease.
AB  - Epstein-Barr virus (EBV) was identified in a subset of cases of Hodgkin's disease
      (HD) and in some non-Hodgkin's lymphomas (NHLs), particularly those associated
      with immunodeficiency. Because patients with HD have associated immune system
      defects, we hypothesized that EBV might be involved in NHLs associated with HD.
      Using fixed paraffin sections and in situ hybridization for EBV EBER1 RNA, we
      studied 12 cases of composite NHL + HD, two patients with NHL who simultaneously
      also had HD involving a different site (simultaneous HD and NHL), 14 NHLs arising
      in patients who previously had HD, and seven NHLs from patients who subsequently
      developed HD. Epstein-Barr virus was identified most frequently in composite NHL
      + HD. Five (42%) cases of composite NHL + HD contained EBV in Reed-Sternberg and
      Hodgkin cells, four of which also had EBV-positive NHLs, diffuse mixed or large
      cell type, with 10 to more than 50 EBV-positive cells per x400 microscopic field.
      These results suggest that in this subset of four cases, both the NHL and HD
      components may have arisen from the same EBV-infected progenitor cell. We did not
      find EBV in two cases of simultaneous NHL and HD or in seven NHLs preceding
      development of HD. We identified EBV in only two of 14 NHLs following HD, one
      small noncleaved cell lymphoma and one plasmacytoma, both containing more than 50
      EBV-positive cells per x400 microscopic field. These results suggest that EBV
      plays a minimal role in NHLs associated with HD, with the exception of composite
      NHL + HD. Hodgkin's disease-associated immune defects may be involved in the
      pathogenesis of a subset of NHLs following HD, but the exact pathogenesis of most
      NHLs associated with HD remains uncertain. Parallels with the high-grade Burkitt
      like lymphomas associated with human immunodeficiency virus infection are noted.

PMID- 8279629
TI  - Epithelioid angiosarcoma of the adrenal glands. A clinicopathologic study of nine
      cases with a discussion of the implications of finding "epithelial-specific"
      markers.
AB  - Adrenal epithelioid angiosarcomas (AEA) are rare neoplasms. We report the
      clinicopathologic features of nine cases of AEA. AEA occurred most frequently in
      the sixth and seventh decades of life (age range, 45-85 years; median, 60); five
      cases occurred in men and four in women. Presenting symptoms included abdominal
      mass with or without pain, weight loss, fever, and weakness. Two cases were
      asymptomatic; one was discovered during evaluation for other disease(s) and the
      other at autopsy. All neoplasms were nonfunctioning. Radiographic evaluation
      demonstrated suprarenal or retroperitoneal neoplasms ranging in size from 6 to 10
      cm in greatest dimension. Histologically, the neoplasms were invasive,
      predominantly arranged in solid sheets or nests, and composed of epithelioid
      cells. Endothelial cell differentiation was suggested by the transition areas
      between dilated anastomotic vascular spaces and the sheet-like growth, the
      cytomorphologic similarity between the endothelial cells lining the discernible
      vascular spaces and those seen in the solid foci, and the presence of
      intracytoplasmic vacuolization occasionally containing red blood cells.
      Endothelial derivation was confirmed by immunohistochemistry including Factor
      VIII-related antigen (FVIII), CD-34 (hematopoetic progenitor cell antigen),
      and/or Ulex europaeus agglutinin-1 lectin immunoreactivity (UEA-1) and by
      ultrastructural findings, including rod-shaped microtubulated bodies and
      intracytoplasmic lumen formation. In addition, cytokeratin reactivity was seen in
      seven cases, and B72.3 (tumor-associated glycoprotein-72) reactivity was seen in
      six. Surgical resection was the treatment of choice, occasionally supplemented by
      chemotherapy. Three patients are presently alive, free of disease, at 13, 11, and
      6 years following diagnosis. Three died with metastatic AEA of the lung, and
      three died of unrelated causes.

PMID- 8279630
TI  - Sinus histiocytosis of pelvic lymph nodes after hip replacement. A histiocytic
      proliferation induced by cobalt-chromium and titanium.
AB  - Six men who had undergone hip replacements for degenerative joint disease or
      trauma subsequently had radical prostatectomies or cystoprostatectomies with
      bilateral pelvic lymph node dissections for adenocarcinoma of the prostate or
      transitional cell carcinoma of the urinary bladder. The hip prostheses implanted
      in three patients were known to contain cobalt-chromium alloy and titanium. The
      pelvic lymph nodes ipsilateral to the hip prosthesis in five patients and the
      bilateral pelvic nodes in the only patient with bilateral hip prosthesis had dark
      brown or black cut surfaces. These lymph nodes did not contain carcinoma but
      showed florid sinus histiocytosis characterized by large polygonal histiocytes
      filling and expanding sinuses and interfollicular regions. The foamy histiocytes
      contained cobalt-chromium and titanium microparticles by light microscopy,
      ultrastructure, and energy-dispersive x-ray microanalysis. The lymph nodes
      uninvolved by the histiocytic reaction lacked the heavy metal microparticles.
      Four cases were found to have a small number of polyethylene particles, which
      might have contributed to the histiocytic response. By immunohistochemistry, the
      foamy cells displayed immunoreactivity for lysozyme, alpha-1-antitrypsin, alpha-1
      antichymotrypsin, and cathepsin D, providing additional support for their
      histiocytic derivation. To our knowledge, this is the first time that
      microparticles of cobalt-chromium and titanium that migrate from hip prostheses
      to pelvic lymph nodes have been shown to elicit a distinctive type of florid
      sinus histiocytosis. Pathologists should be aware of this characteristic foreign
      body tissue response to avoid confusion with other types of sinus histiocytosis
      or with metastatic carcinoma.

PMID- 8279631
TI  - Primary autoimmune cholangitis. An alternative to antimitochondrial antibody
      negative primary biliary cirrhosis.
AB  - The authors report the clinical and liver biopsy features of nine patients with
      primary autoimmune cholangitis, a unique form of chronic nonsuppurative
      destructive cholangitis associated with high-titer serum antinuclear antibodies,
      including eight women and one man; their median age was 51 years. All patients
      showed cholestatic hepatic enzyme profiles (median gamma glutamyl transferase and
      alkaline phosphatase, 800 U/L and 700 U/L, respectively). The median antinuclear
      antibody titer was 1:1,280 (range, 1:640-1:2,560). All patients' sera were
      negative for antimitochondrial antibodies; six were also nonreactive for anti-M2
      mitochondrial autoantigens. Liver biopsies showed marked paucity of interlobular
      bile ducts (median percentage of portal tracts containing bile ducts, 11%; range,
      0-50%). Granulomatous cholangitis was present in two cases; five livers showed
      the pattern of bile ductular proliferative piecemeal necrosis. Seven patients
      were treated with prednisone and azathioprine without clinical benefit. During
      follow-up of 1 to 5 years, disease has progressed in seven patients, including
      four who have developed other autoimmune conditions. Although clinically,
      biochemically, and histopathologically comparable to primary biliary cirrhosis,
      autoimmune cholangitis abdicates antimitochondrial antibodies in favor of
      antinuclear antibodies. It represents a distinctive subset of antimitochondrial
      antibody-negative adult ductopenic disorders, for which conventional
      immunosuppressive therapy does not appear warranted.

PMID- 8279632
TI  - Human retroviruses in Amerindians of Colombia: high prevalence of human T cell
      lymphotropic virus type II infection among the Tunebo Indians.
AB  - The coexistence of infection with human T lymphotropic virus types I and II (HTLV
      I and HTLV-II) has been demonstrated recently among the Wayuu Indians from the
      Guajira region of Colombia. To ascertain if other Indian groups in Colombia are
      similarly infected, we tested 1,250 sera, collected between 1990 and 1992 from 18
      culturally distinct Amerindian tribes living in widely separated regions, for IgG
      antibodies against HTLV-I/II using enzyme-linked immunosorbent assay (ELISA) and
      Western blot. Sera were also tested for antibodies against human immunodeficiency
      virus types 1 and 2 (HIV-1 and HIV-2) to investigate the overall burden of
      retrovirus infection in these semi-isolated indigenous groups. A total of 33 of
      the 1,250 samples were repeatedly reactive to HTLV-I/II antigens by ELISA, and of
      these, three sera from Waunana/Noanama Indians from the Choco area and two sera
      from Tunebo Indians from the Santander region were found to be infected with HTLV
      I and HTLV-II, respectively, as verified by Western blot and differential ELISA.
      Thus, despite the small sample size, the overall seroprevalences for HTLV-I and
      HTLV-II infection among the Waunana/Noanama and Tunebo Indians were 2.1% and
      5.0%, respectively. In contrast, none of the 29 Indians who exhibited reactivity
      to HIV-1/2 by ELISA were seropositive by Western blot. This study adds the Tunebo
      to the expanding list of Amerindian groups with high prevalences of HTLV-II
      infection. Further intensive investigations of such indigenous populations will
      clarify the natural history and disease potential of HTLV-II infection.

PMID- 8279634
TI  - Effect of environmental temperature on the vector competence of Aedes
      taeniorhynchus for Rift Valley fever and Venezuelan equine encephalitis viruses.
AB  - Studies were conducted to determine the effect of environmental temperature on
      the susceptibility of Aedes taeniorhynchus mosquitoes for Venezuelan equine
      encephalitis (VEE) and Rift Valley fever (RVF) viruses. Mosquitoes reared at low
      temperature (19 degrees C) were significantly more susceptible to infection with
      RVF virus (infection rate = 70%, 158 of 226) than were those mosquitoes reared at
      26 degrees C (infection rate = 48%, 135 of 280), regardless of the temperature at
      which mosquitoes were held after exposure to virus (19 or 26 degrees C).
      Likewise, for Ae. taeniorhynchus exposed to VEE virus, the infection rate in
      mosquitoes reared at low temperature (97%, 236 of 243) was significantly greater
      than was that for mosquitoes reared at 26 degrees C (78%, 217 of 280), regardless
      of the temperature at which mosquitoes were held after exposure to virus (19 or
      26 degrees C). Conversely, in mosquitoes infected with either RVF or VEE virus,
      virus disseminated from the midgut to the hemocoel more rapidly in mosquitoes
      held at 26 degrees C than in those held at 19 degrees C, regardless of the
      rearing temperature. Thus, a combination of low larval-rearing temperature and
      warm adult-holding temperature resulted in the most efficient mosquito
      transmission of both viruses.

PMID- 8279633
TI  - Selectivity of human T lymphotropic virus type-1 (HTLV-1) and HTLV-2 infection
      among different populations in Brazil.
AB  - A seroprevalence study for human T lymphotropic virus type-1 (HTLV-1) and HTLV-2
      was conducted in Sao Paulo, Brazil among 2,312 individuals that included
      following groups: 1,148 volunteer blood donors, 37 patients with tropical spastic
      paraparesis (TSP), 53 with lymphoproliferative disorders, 171 with a history of
      multiple blood transfusions, 268 human immunodeficiency virus type-1 (HIV-1)
      seropositive subjects, and 635 Amazonian Indians. Antibodies to HTLV-1/2 were
      screened by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western
      blot and/or radioimmunoprecipitation. The differentiation of HTLV-1 and HTLV-2
      was achieved using a synthetic recombinant peptide (rgp46) ELISA. We confirmed
      the presence of HTLV-1 infection in Brazil, both in blood donors (0.4%) and in
      patients exposed to blood transfusions (2.9%), as well as the occurrence of HTLV
      1-associated TSP (11 patients, or 30% of all TSP cases) and adult T cell
      leukemia/lymphoma (two cases, or 3.5% of all hematologic malignancies). The HIV-1
      infected individuals were shown to be coinfected (8.9%) with either HTLV-1 or
      HTLV-2. All HIV-1 and HTLV-2 coinfected individuals were intravenous drug
      abusers. In addition, we also demonstrated the presence of HTLV-2 (4.7%), and
      HTLV-1/2 (0.8%) in tribes of Amazonian Indians who lived in the eastern Amazon
      basin (southeastern State of Para). The selectivity of these retroviral
      infections in particular groups is emphasized, as well as the need for HTLV-1/2
      screening of all blood donors in Brazil as a public health measure.

PMID- 8279635
TI  - Eastern equine encephalitis (EEE): a description of the 1989 outbreak, recent
      epidemiologic trends, and the association of rainfall with EEE occurrence.
AB  - An Eastern equine encephalitis (EEE) outbreak in 1989 led to nine human and 196
      equine cases, chiefly in coastal Atlantic and Gulf Coast counties. In the past
      two decades, EEE age-specific incidence and mortality rates have declined
      compared with earlier years. Analysis of rainfall patterns in areas where human
      EEE cases occurred between 1983 and 1989 revealed an association between
      occurrence of human cases and excess rainfall. The association was stronger with
      data from local weather stations than from statewide rainfall averages and the
      predictive models were best when applied to northern states. The sensitivity and
      specificity of these measures varied, depending on the model used, but the
      positive predictive value was no better than 50%, regardless of the rainfall
      model applied.

PMID- 8279636
TI  - Ross River virus isolations from mosquitoes in arid regions of Western Australia:
      implication of vertical transmission as a means of persistence of the virus.
AB  - Outbreaks of mosquito-borne Ross River (RR) virus disease (epidemic
      polyarthritis) occur suddenly in the arid north and interior of the State of
      Western Australia, often within a few weeks of heavy rainfall. Between outbreaks,
      these regions may undergo long periods of drought, with little or no mosquito or
      arbovirus activity. The means by which RR virus is reintroduced or reactivated in
      these areas when environmental conditions favor mosquito-borne virus activity are
      unknown. In this paper, we describe isolations of RR virus from eight mosquito
      species trapped at two different locations, one coastal and one inland, in the
      arid Pilbara region of Western Australia, prior to outbreaks of epidemic
      polyarthritis. The isolation of RR virus has not been previously reported for
      five of these species and the isolations from the other three species are new
      records for Western Australia. The timing and number of isolations of RR virus
      from Aedes (Ochlerotatus) vigilax (Skuse, 1889) implicate that species as a
      vector of the virus on the Pilbara coast. Significantly, RR virus was isolated
      from pools of male Ae. vigilax and male Ae. (Macleaya) tremulus (Theobald, 1903)
      mosquitoes. This is the first report of RR virus (or other Australian arbovirus)
      isolates from wild-caught male mosquitoes. Both Ae. vigilax and Ae. tremulus have
      desiccation-resistant eggs that can survive long periods of drought, making them
      ideal candidates for the overwintering of arboviruses. The findings implicate
      vertical transmission as a means of persistence of RR virus in arid regions of
      Australia and therefore offer a likely explanation for the sudden recurrence of
      virus activity after heavy rains.

PMID- 8279637
TI  - Is Schistosoma mansoni replacing Schistosoma haematobium in the Fayoum?
AB  - Schistosoma mansoni is progressively replacing S. haematobium along the Nile
      River in Egypt. This change has occurred in the past 15-20 years following
      construction of the Aswan High Dam in the 1960s. The cause is a shift in relative
      abundance of the snail vectors Biomphalaria alexandrina and Bulinus truncatus.
      Biomphalaria is increasing while the latter has disappeared from a village in the
      Fayoum where formerly only schistosomiasis haematobia was endemic. A cross
      sectional household survey in this village in 1991 showed the following
      prevalence values: S. mansoni, 22.3%; S. haematobium, 3.4%; and mixed infections,
      2.8%. Only two children less than 10 years of age had S. haematobium infections.
      A review of the local Ministry of Health records showed that 1) both species were
      parasitologically diagnosed during the past 7.5 years, 2) Biomphalaria had been
      abundantly present in the local waterways for the past 10 years and has been
      found infected with S. mansoni since 1985, 3) Bulinus has not been detected in
      the local canals and drains since 1986 and the few found between 1981 and 1985
      were not infected, and 4) Biomphalaria in this village and in two others in the
      Fayoum were believed infected by laborers from the Delta who helped build schools
      in 1984. This change in the distribution of schistosomiasis will impact upon
      public health and medical practice in Middle and Upper Egypt as it already has in
      Lower Egypt.

PMID- 8279638
TI  - Epidemiology of Schistosoma mansoni infection in a recently exposed community in
      northern Senegal.
AB  - The epidemiology of Schistosoma mansoni infection was investigated in Ndombo, a
      village in the epicenter of a very recent outbreak of schistosomiasis in northern
      Senegal. Repeated fecal egg counts and antigen detection in urine and serum were
      carried out in a random population sample (n = 422). Eggs were found in 91% of
      the subjects, with 41% excreting > 1,000 eggs per gram of feces (epg) (mean egg
      load of 646 epg). The prevalence was almost 100% in groups greater than five
      years of age. In spite of the supposed absence of acquired immunity, intensities
      of infection decreased strongly in adults. Antigen detection confirmed the high
      prevalence and intensity of infection and the age-related distribution of worm
      loads. The emergence of this new focus is probably due to the ecologic impact of
      newly built dams and the extension of irrigation projects in the Senegal basin.

PMID- 8279639
TI  - Age-specific prevalence of Plasmodium falciparum among six populations with
      limited histories of exposure to endemic malaria.
AB  - The age-specific prevalence of Plasmodium falciparum parasitemia among residents
      of six villages in northeastern Irian Jaya, Indonesia, has been measured for a
      period of five years. All study subjects were transmigrants from Java living in
      Irian Jaya for three weeks to 72 months, depending upon the village and point of
      measurement. Fifteen separate estimates of prevalence were obtained from 4,554
      Giemsa-stained thick blood films from 91 to 701 people (mean sample size = 304)
      among the six villages. The prevalence of parasitemia among people who had lived
      in Irian Jaya for less than one year did not decrease as a function of age,
      except in one village at eight months. In contrast, after 16 months to two years
      or more of residence, the prevalence of parasitemia decreased markedly with
      increasing age beyond 6-10 or 11-15 years. Social, behavioral, or entomologic
      characteristics of these populations did not explain the decreasing prevalence of
      parasitemia with age. An age-dependent naturally acquired protective immunity
      appeared to develop in all of these villages after 1-2 years of exposure to
      hyperendemic malaria.

PMID- 8279640
TI  - Plasma antioxidants and lipid peroxidation products in falciparum malaria.
AB  - To investigate the influence of Plasmodium falciparum malaria on plasma
      antioxidants and lipid peroxidation, plasma ascorbate, urate, total protein and
      albumin, ceruloplasmin and malondialdehyde (MDA) were determined in two groups of
      42 patients each, one with mild and the other with severe falciparum malaria, and
      in an equal number of age- and sex-matched control subjects. Plasma MDA was found
      to be significantly higher in malaria patients, and the increase was proportional
      to the severity of the disease. Of the antioxidants, ascorbate and albumin
      decreased with severity of disease while urate and ceruloplasmin increased. Only
      ascorbate correlated inversely with MDA both in mild (r = -0.341, P < 0.05) and
      severe malaria (r = 0.545, P < 0.01). While plasma albumin correlated inversely
      (r = -0.442, P < 0.01), urate and ceruloplasmin correlated directly (r = 0.419, P
      < 0.01 and r = 0.349, P < 0.05, respectively) only in patients with severe
      malaria. These antioxidants also correlated well with markers of disease
      severity, indicating the influence of disease severity in regulating their levels
      in plasma. The presence of significant quantities of ascorbate and albumin, along
      with increases in some of the other antioxidants and MDA, indicates
      ineffectiveness of the antioxidant defense system in controlling plasma lipid
      peroxide content. Increased amounts of thiobarbituric acid-reactive material
      could have been the result of spillover from increased tissue peroxidation or the
      presence of pro-oxidants in malarial plasma.

PMID- 8279641
TI  - Evidence through crossmating experiments of a species complex in Anopheles
      pseudopunctipennis sensu lato: a primary malaria vector of the American
      continent.
AB  - Crossmating experiments were conducted to determine if postmating reproductive
      barriers are involved in the maintenance of genetic divergence among populations
      of Anopheles pseudopunctipennis sensu lato, a primary malaria vector of the
      American continent. Reciprocal crosses were conducted between colony and wild
      strains from Mexico, Bolivia, and Peru. Hybridization experiments revealed
      unidirectional male/female hybrid sterility in crosses between Mexican females
      and South American males. The data presented provide the first evidence that
      genetic differences exist among geographic strains of An. pseudopunctipennis in
      neotropical America. There is a consistent pattern suggesting the presence of at
      least two allopatric sibling species. One species occurs in central Mexico, the
      other in the South American Andean Cordillera.

PMID- 8279642
TI  - Microfilarial densities, hematologic changes, and serum antibody levels in Loa
      loa-infected rhesus monkeys (Macaca mulatta).
AB  - To better define Loa loa infection in the rhesus monkey and assess the potential
      usefulness of this host as a model for studies of human loiasis, 12 monkeys (four
      splenectomized and eight nonsplenectomized) were inoculated with L. loa infective
      larvae. Microfilaremia and hematologic changes as well as parasite-specific
      antibody were assessed as a function of time in these animals. Eleven of 12
      inoculated monkeys became microfilaremic. Splenectomized animals had moderate
      (250-1,000) to low (< 250) numbers of microfilariae per milliliter (mf/ml),
      whereas the mf/ml in nonsplenectomized animals varied from high (> 1,000) to low.
      A significant increase in total leukocyte and lymphocyte numbers was seen in
      animals with moderate-to-low mf/ml but not in animals with high mf/ml mainly
      because of variations between animals in the latter group, rather than a direct
      consequence of increased mf numbers. All infected animals developed an
      eosinophilia before patency, suggesting the adult worms most likely contribute to
      this phenomenon. As the infection progressed, the eosinophil numbers decreased
      significantly. Although splenectomized animals overall had slightly higher
      numbers of total leukocytes (lymphocytes and eosinophils), these hematologic
      changes as a function of time were not significantly different from those in
      nonsplenectomized animals. Parasite-specific IgG antibody was increased
      significantly before patency in all animals and with the exception of the one
      amicrofilaremic animal, it decreased after patency. This study shows that
      splenectomy of rhesus monkeys prior to L. loa inoculation does not enhance the
      microfilarial density nor does it adversely affect eosinophilia or antibody
      production.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279643
TI  - Dot immunoassay with biotinylated antigen for determination of antibodies against
      the circulating cathodic antigen (CCA) in schistosomiasis japonica.
AB  - Based on the fact that schistosomiasis patients in both the acute and chronic
      phase of the infection show a strong humoral immune response against the gut
      associated circulating cathodic antigen, a simple and sensitive dot immunobinding
      assay for schistosomiasis japonica was developed. Circulating cathodic antigen
      that had been purified by immunoadsorption using monoclonal antibody was
      biotinylated with biotin aminocaproylhydrazide via the carbohydrate moiety of the
      antigen. Serum samples dotted onto nitrocellulose strips were then tested in an
      assay involving a combined incubation step of biotinylated antigen and
      streptavidin peroxidase, and a subsequent staining; the total assay time was 1.5
      hr. Assaying the sera of 105 uninfected controls and 104 Schistosoma japonicum
      infected individuals showed a specificity of 99.0%, and sensitivities of 96.2%
      (acute infections) and 94.1% (chronic infections). The described assay is
      economic, rapid, and reproducible and lends itself to use under field conditions.

PMID- 8279644
TI  - Induction of protective immunity against larval Onchocerca volvulus in a mouse
      model.
AB  - BALB/cBYJ mice were immunized against larval Onchocerca volvulus by subcutaneous
      injection of normal, irradiated, or freeze-thaw-killed Onchocerca sp. larvae. The
      mice received challenge infections of O. volvulus third-stage larva (L3)
      contained in diffusion chambers implanted subcutaneously. At two-weeks
      postinfection, the diffusion chambers were removed and larval survival was
      assessed. When mice were immunized a single time with 35-krad-irradiated or
      normal O. volvulus L3, there was a significant reduction in the survival of
      challenge parasites. However, there was little or no reduction in challenge worm
      survival when mice were immunized a single time with freeze-thaw-killed O.
      volvulus L3 or fourth-stage larva (L4), or irradiated O. lienalis L3. When a
      second dose of freeze-thaw killed O. volvulus L3 or irradiated O. lienalis L3 was
      administered, there was a significant reduction in parasite survival in immunized
      mice. Immunization with O. volvulus L4 or a combination of L3 and L4 failed to
      confer protection. These results demonstrate that mice can be immunized against
      larval O. volvulus and that diffusion chambers are an efficient method for
      studying protective immunity to this parasite in a mouse model.

PMID- 8279645
TI  - Incidence, management, and outcome of childhood empyema: a prospective study of
      children in Cambodian refugee camps.
AB  - To determine the incidence, outcome, and optimal management of empyema, all
      children less than 15 years of age admitted to Khao-I-Dang Hospital with a
      diagnosis of empyema during a 23-month period were prospectively studied. Khao-I
      Dang Hospital provides care to 137,000 Cambodian children residing in eight
      refugee camps along the Thai-Cambodian border. Ninety-eight children with empyema
      were identified, for an annual incidence of 0.37 cases per 1,000 children. All
      patients had chest tubes inserted on admission, and all were treated with
      parenteral antibiotics, which included chloramphenicol in 92% of the patients and
      cloxacillin in 72%. Patients were hospitalized a mean of 30 days, and chest tubes
      were in place for a mean of 12 days. Surgery was performed on four patients who
      had bronchopleural fistulas that persisted for more than 14 days. Only one (1%)
      of the 70 patients treated with cloxacillin required thoracotomy, compared with
      three (11%) of the 28 patients who did not receive cloxacillin (P = 0.07). In a
      multiple regression analysis, the presence of pneumatoceles or mediastinal shift
      on admission chest radiograph, a history of tuberculosis in the family, and an
      age of more than five years were predictive of a longer duration of chest tube
      drainage. No patient died in the hospital, and only one patient died in the six
      months following discharge from the hospital. Chest radiographs that were
      obtained six months after discharge in 25 patients were all essentially normal,
      despite marked abnormalities on chest radiographs obtained at discharge. In
      summary, conservative medical management with the use of chest tubes for these 98
      children with empyema resulted in a mortality rate of 1.0%, and should be
      considered as an effective alternative to the surgical management of patients
      presenting with this complication.

PMID- 8279646
TI  - Increased in vivo activation of neutrophils and complement in sickle cell
      disease.
AB  - Eight patients with homozygous sickle cell anemia, 15 heterozygotes, and eight
      control individuals were investigated with respect to plasma concentrations of
      the inflammatory markers lysozyme and myeloperoxidase and the complement
      activation marker C3d. The patients showed significantly increased levels of
      myeloperoxidase and C3d, but not lysozyme, compared with the heterozygotes and
      the controls. The heterozygotes were also significantly different from the
      controls with regard to C3d concentration. The concentrations of myeloperoxidase
      and C3d in plasma showed a significant inverse correlation with the hemoglobin
      concentration. Myeloperoxidase and C3d showed a significant positive correlation.
      This suggests a role for the neutrophil and the complement system in the
      pathophysiology of sickle cell disease.

PMID- 8279647
TI  - Comparison of single-dose diethylcarbamazine and ivermectin for treatment of
      bancroftian filariasis in Papua New Guinea.
AB  - This double-blind study compared the clinical safety and parasitologic efficacy
      of single-dose regimens of diethylcarbamazine (DEC) and ivermectin for treatment
      of bancroftian filariasis in Papua New Guinea. Five groups of 10 men each with
      mean levels of parasitemia ranging from 2,985 to 5,185 microfilariae (mf)/ml were
      given DEC (6 mg/kg of body weight one time or 1 mg/kg, then 6 mg/kg four days
      later) or ivermectin (220 micrograms/kg; 20 micrograms/kg, then 200 micrograms/kg
      four days later or 20 micrograms/kg, then 400 micrograms/kg four days later). No
      significant side effects (e.g., acute adenolymphangitis, fever lasting more than
      eight hours, hypotension) were observed in any of the five treatment groups. The
      magnitude of reduction in microfilaremia was greater (P < 0.01) for the three
      ivermectin groups versus the two DEC groups in the first 30 days after drug
      administration (mf levels < 1% of pretreatment values versus 22.6-41.5%,
      respectively). At 90 and 180 days, mf levels continued to decrease in the DEC
      groups whereas they increased in the ivermectin groups given a total dose of 220
      micrograms/kg. Eighteen months after drug administration, individuals given DEC
      or 420 micrograms/kg of ivermectin had the greatest degree of reduction in
      microfilaremia (86-90% compared with the pretreatment values). Decreases in
      parasite antigenemia measured by enzyme-linked immunosorbent assay for a secreted
      200-kD adult worm antigen were greatest for the single-dose DEC group (39.7%
      decrease relative to the pretreatment level versus 7.8-15.7% for the ivermectin
      groups). These results indicate that single-dose DEC and ivermectin are well
      tolerated by Wuchereria bancrofti-infected individuals with high levels of
      microfilaremia.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279648
TI  - Morphologic effects of artemether on Plasmodium falciparum in Aotus trivirgatus.
AB  - The effects of artemether on the morphology of Plasmodium falciparum were studied
      in an owl monkey (Aotus trivirgatus) when parasitemia reached 33% and the animal
      became severely ill. The earliest and the most distinctive ultrastructural
      changes following the administration of artemether were marked swelling of the
      mitochondria in the parasites, followed by the appearance of electron-dense
      chromatin materials in the nuclei and clumping of ribosomes. The initial change
      was observed within 2 hr of administration of the drug. These findings correlate
      well with the rapid and effective action of artemether, which has been
      demonstrated in human clinical trials.

PMID- 8279649
TI  - Brainstem auditory evoked potentials following meningitis in children.
AB  - The report concerns findings for brainstem auditory evoked potentials (BAEPs)
      recorded in 116 children, aged between a few days and 7 years, having suffered
      from bacterial meningitis. 26% of cases occurred between birth and 6 months, 55%
      between 6 months and 2 years, and 19% after 2 years of age. Hemophilus was the
      most common bacteria (49%), followed by Pneumococcus (22%) and Meningococcus
      (15%). Neurological complications were found in 30% of the meningitis cases and
      accounted for 85% of all complications found. 29% of BAEPs were abnormal, of
      which 47% revealed transmission, 32% endocochlear and 21% retrocochlear
      impairment. Transmission impairment mainly occurred before the age of 2 years
      (88%), most frequently in meningococcus meningitis cases (44%), and independently
      of neurological complications. Retrocochlear impairment was found in association
      with neurological complications in 71% of cases. Endocochlear BAEP damage was
      found in 9.5% of cases, half of which were bilateral and total, representing
      cophosis: it was found at all ages, and without any particular associated
      neurological complication. Hemophilus was the commonest bacterial agent in
      endocochlear cases overall, with Pneumococcus underlying 50% of cophosis cases.
      The study shows BAEP recording in association with a clinical ear examination is
      useful following childhood bacterial meningitis, screening for definitive
      endocochlear and deafness, distinguishing total from partial hearing-loss and
      indicating suitable treatment.

PMID- 8279650
TI  - High doses of penicillin decreases [3H]flunitrazepam binding sites in rat neuron
      primary culture.
AB  - Penicillin (PC) neurotoxicity (convulsions and encephalopathy) is considered to
      be due to GABAergic inhibition. The effects of penicillin G(PCG) on
      [3H]flunitrazepam (FNZ) binding in rat neuron-enriched primary cultures was
      examined to assess the role of the benzodiazepine (BDZ) receptor in the
      neurotoxicity. PCG application for 24 h induced a significant decrease in [3H]FNZ
      binding activity at 10(-3) M, and a decrease in available receptor number (Bmax)
      at 10(-2) M, without obvious cell damage. Pre-application of the BDZ receptor
      antagonist, Ro-15-1788, prevented the PC-induced decrease in [3H]FNZ binding
      activity. Therefore, PC seems to reduce the number of BDZ receptors through a
      direct effect on this receptor, which is a part of the major inhibitory system in
      mammalian brain; the GABAergic macromolecular receptor complex. This decrease in
      BDZ receptors may play a role in PC-induced neurotoxicity, especially
      encephalopathy.

PMID- 8279651
TI  - Incontinentia pigmenti: clinical and neuroradiologic features.
AB  - Developmental brain malformations and destructive processes of unknown etiology
      were described in incontinentia pigmenti (IP). Two patients, a male and a female,
      with characteristic skin lesions and central nervous system (CNS) involvement are
      reported. Neuroradiological examinations revealed hypoplasia of corpus callosum,
      neuronal heterotopias, and periventricular white matter damage. No specific
      infectious, inflammatory, or metabolic abnormalities were identified. These
      neuroradiographic findings may suggest that an ischemic pathogenetic mechanism
      occurred prenatally. We speculate that the brain damage in IP may occur during
      CNS development and in successive stages. Magnetic resonance imaging appears more
      useful to detect white matter lesions and brain malformations in patients with
      IP.

PMID- 8279652
TI  - A case of Canavan disease: the first biochemically proven case in a Japanese
      girl.
AB  - Canavan disease (CD) has only been diagnosed on autopsy or brain biopsy, however,
      specific biochemical markers, such as N-acetylaspartic acid (NAA) and
      aspartoacylase activity, have recently been described in CD. We report a case of
      CD having the above biochemical markers. High levels of NAA were found in her
      urine, serum and CSF. Fibroblasts did not exhibit aspartoacylase activity.
      Clinically, she presented progressive psychomotor retardation, cerebellar signs,
      pyramidal signs and relative megalencephaly. CT and MRI showed findings of
      leukodystrophy. The evoked potentials showed widespread involvement in the
      brainstem. Magnetic resonance spectra showed a high level of NAA in the white
      matter. In Japan, this case is the first of CD determined on the basis of
      biochemical markers.

PMID- 8279653
TI  - Dominantly inherited early-onset non-progressive cerebellar ataxia syndrome.
AB  - A mother and daughter with suspected dominantly inherited, early-onset, non
      progressive cerebellar ataxia syndrome have been reported. A review of the
      literature and the clinical features of the present cases revealed the nosologic
      features of this rare disorder, possibly dominant inheritance, floppiness and
      delayed milestones preceding early-onset mild cerebellar ataxia, non-progressive
      clinical course, retained or even brisk tendon reflexes without pyramidal tract
      involvement, normal or slightly delayed intelligence, and occasional nystagmus.
      Neuroimaging reveals selective involvement of the cerebellum, which is prominent
      in the vermis and the anterior part of the hemispheres.

PMID- 8279654
TI  - Adrenoleukomyeloneuropathy presenting as cerebellar ataxia in a young child: a
      probable variant of adrenoleukodystrophy.
AB  - A child aged 5 years 7 months was diagnosed as suffering from
      adrenoleukomyeloneuropathy (ALMN). The first sign was ataxia, and high intensity
      lesions were observed in the cerebellar hemispheres on T2-weighted brain MRI. His
      condition progressed rapidly to a vegetative state in 1 year. When aged 7 years 3
      months adrenal insufficiency supervened and his skin turned dark. Rectal biopsy
      revealed linear cytoplasmic inclusions in macrophages in the rectal membrane. At
      the age of 8 years 2 months, an analysis of very long-chain fatty acids of
      sphingomycin in plasma led to the final diagnosis. At the age of 10 years,
      cerebellar and cerebral atrophy were prominent and diffuse high intensity lesions
      were noted in the cerebellum and cerebrum. An onset below 9 years of age has not
      previously been documented in ALMN.

PMID- 8279655
TI  - Decreased 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) in patients with
      Lesch-Nyhan syndrome.
AB  - The coagulation abnormality in patients with Lesch-Nyhan syndrome (LNS) prompted
      us to examine 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha), a stable
      metabolite of prostacyclin (PGI2). Plasma levels of 6-keto PGF1 alpha were
      significantly low in 4 patients with LNS, but they were elevated after
      discontinuation of allopurinol. Other indicators of coagulation and fibrinolysis
      systems did not change after the discontinuation of allopurinol. PGI2 prevents
      the production of superoxide which is formed after cerebral ischemia. The
      potential source of superoxide is xanthine oxidase which is inhibited by
      allopurinol. It is assumed that plasma PGI2 increased in response to formed
      superoxide because xanthine oxidase inhibition was abolished after
      discontinuation of allopurinol.

PMID- 8279656
TI  - Idiopathic lactic acidemia with developmental delay and type 1 muscle fiber
      atrophy: report of two patients.
AB  - Two infants with generalized muscle hypotonia with mild muscle weakness and
      markedly delayed developmental milestones, had high lactate levels in serum and
      cerebrospinal fluid from early infancy. Biochemical and morphologic studies of
      biopsied muscles disclosed no abnormality except for type 1 fiber atrophy, which
      was quite different from patients with central nervous involvement with type 2
      fiber atrophy. In both patients, the disease was not progressive and lactate
      levels gradually decreased. Although no metabolic defect was found, these
      patients probably shared common pathogenetic mechanism.

PMID- 8279657
TI  - Thalamic hyperdensity--is it a diagnostic marker for Sandhoff disease?
AB  - Sandhoff disease, also known as GM2-gangliosidoses variant 0, is caused by the
      deficient activity of both hexosaminidase A and hexosaminidase B. We report a 15
      month-old boy diagnosed with Sandhoff disease by demonstrating the enzyme
      deficiency. The interesting finding was bilateral thalamic hyperdensity on the CT
      scan. The hyperdensity in all previously published cases was homogeneous and
      symmetric and limited to the thalamus; the cause still remains unknown. We
      suggest that the finding of dense thalami may be useful as a specific diagnostic
      criterion for the GM2-gangliosidoses and especially for Sandhoff disease.

PMID- 8279658
TI  - Alcohol consumption in rats potentiates the deleterious effect of gram-negative
      sepsis on hepatic hyaluronan uptake.
AB  - The role of hepatic sinusoidal endothelial cells (SECs) in the pathologic changes
      of the liver associated with alcohol consumption is not fully understood. The
      measurement of hyaluronan (HA) uptake by the SECs provides a useful means for
      assessing the functional state of these cells. In this study, we determined the
      effect of acute and chronic exposure to alcohol in rats in the absence and
      presence of subcutaneous Escherichia coli-induced sepsis on plasma HA
      concentration and HA uptake by the isolated, perfused liver. Rats were
      administered ethanol (two doses of 0.2 g/100 g body weight, intraperitoneally, 24
      and 15 hr before killing) or fed a liquid diet for 8-10 weeks, containing alcohol
      (36% of the total calories) or dextrin (in isocaloric amounts). Twenty-one hr
      before euthanizing for liver perfusion, animals were injected subcutaneously with
      live E. coli (sepsis) or sterile saline (control). Neither acute nor chronic
      alcohol exposure by themselves altered plasma HA levels. However, both treatments
      exacerbated the hyperhyaluronanemic effect of sepsis. Thus, in acutely alcohol
      treated rats, sepsis induced a 187% (p < 0.05) increase in plasma levels of HA,
      whereas in nonalcohol septic rats, the increase was only 54% (p < 0.05).
      Likewise, sepsis resulted in a greater increase in the plasma levels of HA (871%)
      in alcohol-fed rats than it did in liquid diet, control-fed rats (323%, p <
      0.05). The rate of HA uptake by the isolated, perfused liver was not altered by
      either acute or chronic alcohol exposure. However, alcohol exposure markedly
      potentiated the inhibitory effect of sepsis on the capacity of the liver to take
      up HA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279659
TI  - Effect of exposure to an alcohol diet for 10 days on the ability of interleukin-1
      beta to release ACTH and corticosterone in the adult ovariectomized female rat.
AB  - Adult ovariectomized female rats were fed an alcohol diet for 10 days. Animals
      fed ad libitum, or fed an isocaloric diet (pair-fed), were also included in all
      experiments. The intravenous injection of interleukin-1 beta caused dose-related
      increases in plasma adrenocorticotropic hormone (ACTH) levels in all three groups
      of rats. However, alcohol-fed animals showed a significant blunting of their
      ACTH, but not corticosterone response, in comparison with rats fed ad libitum or
      pair-fed. In contrast, corticotropin-releasing factor (CRF) injection caused
      overall statistically comparable ACTH secretory rates in all animals, although
      small differences were observed in some cases. Exposure to mild electroshocks for
      30 min significantly increased ACTH values in all animals, but alcohol-fed rats
      again showed blunted release. In this paradigm, pair-fed animals exhibited a
      response that was intermediate between that of the ad libitum and alcohol-fed
      groups. We conclude that chronic alcohol consumption decreases the response of
      the hypothalamic-pituitary axis to cytokines and mild footshocks. This suggests
      that the activity of both CRF nerve terminals in the median eminence, and of CRF
      perikarya in the hypothalamus, is inhibited by this treatment, although pituitary
      responsiveness to CRF appears unchanged.

PMID- 8279660
TI  - Vulnerability of cerebellar granule cells to alcohol-induced cell death
      diminishes with time in culture.
AB  - This study examined the effects of alcohol exposure on the viability of
      cerebellar granule cells in culture. Continuous alcohol exposure, starting 1 day
      after the cultures were established, significantly reduced granule cell numbers,
      even with a single day of exposure to an alcohol concentration as low as 100
      mg/dl. The depletion of cerebellar granule cells by alcohol was concentration
      dependent (greater loss of cells at higher alcohol concentrations) and duration
      dependent (greater loss of cells at longer exposure durations). The loss of
      granule cells also depended on the number of days the granule cells were in
      culture before alcohol exposure. Alcohol was significantly more effective in
      reducing the cell numbers of newly established granule cell cultures (1 day in
      vitro) compared with older cultures (4 or 7 days in vitro). Cell cycle analysis
      established that the cerebellar granule cells did not proliferate in culture,
      indicating that alcohol exposure did not reduce cell numbers by interfering with
      cell proliferation in this system. Instead, alcohol-induced killing of the
      granule cells was the most likely mechanism to account for the depletion of
      granule cells in vitro. Granule cell cultures are a useful in vitro model system
      to study the cellular and molecular aspects of neuronal cell depletion associated
      with fetal alcohol exposure. The potential role of the N-methyl-D-aspartate
      receptor in this alcohol-induced neuronal cell death is discussed.

PMID- 8279661
TI  - Effects of chronic alcohol feeding and murine AIDS virus infection on liver
      antioxidant defense systems in mice.
AB  - Whether ethanol (ETOH) abuse could contribute to the development of acquired
      immunodeficiency syndrome (AIDS) among human immunodeficiency virus (HIV)
      positive drug abusers is a critical question for which little experimental
      information is available. This study was designed to determine if chronic ETOH
      feeding and murine AIDS virus infection cooperatively affected liver antioxidant
      defense systems in C57B1/6 female mice. Mice were divided into two groups and fed
      the Lieber-DeCarli liquid ETOH diet containing ETOH at a concentration to provide
      31% of total caloric intake or an isocaloric liquid control (control) diet in
      which dextrin-maltose replaced ETOH. One week after the initiation of ETOH
      feeding, half of the mice in each diet group (8 mice) were injected
      intraperitoneally with murine retrovirus (MAIDS) stock. After 3 and 5 weeks of
      ETOH feeding, half of the mice in each of the four treatment groups (4 mice) were
      killed, and livers were excised for biochemical analysis. Liver reduced
      glutathione (GSH) levels and activities of glutathione peroxidase (GP),
      glutathione reductase (GR), glutathione transferase (GT), catalase and superoxide
      dismutase (SOD), and serum ETOH concentrations were determined. The results
      demonstrated that serum ETOH concentrations were significantly elevated in ETOH
      MAIDS group when compared with the ETOH group. Moreover, chronic ETOH feeding and
      MAIDS infection independently depressed liver antioxidant defense capability, and
      together led to an additive inhibition of GSH and SOD activities. In addition,
      MAIDS infection inhibited an ETOH-induced increase in catalase and GT activities.
      These results suggest that alcohol abuse could contribute to the development of
      AIDS by inhibiting the protective capability of an infected individual against
      oxidative stress.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279662
TI  - Sensitivity to strychnine seizures is unaltered during ethanol withdrawal.
AB  - Previous research from this laboratory has indicated that animals chronically
      exposed to ethanol and then withdrawn exhibit a variety of symptoms of central
      nervous system hyperexcitability that occur in unique clusters. These clusters of
      symptoms were observed to differ in their duration and in the time of onset
      relative to the time of ethanol withdrawal. In addition, the observed clusters of
      spontaneous seizure events in these animals were seen to correlate with
      differences in sensitivity to seizure-inducing treatments. These results suggest
      that seizure sensitivity during ethanol withdrawal may indicate the involvement
      of multiple, independent, neuronal mechanisms. To investigate this possibility
      further, the following study examined the sensitivity of ethanol-withdrawn
      animals to seizures induced by the glycine antagonist strychnine. Seizure
      sensitivity to strychnine was evaluated at the same times following ethanol
      withdrawal when animals were previously seen to show the differential occurrence
      of spontaneous seizure events and also differences in sensitivity to picrotoxin
      induced seizures. Ethanol-withdrawn animals did not differ in their responses to
      strychnine compared with ethanol-naive controls at any of the times tested. This
      lack of change in seizures induced by antagonism of glycine inhibition occurred
      in spite of the increased sensitivity of similarly treated animals to picrotoxin
      induced seizures at the same test times. These data suggest that chronic ethanol
      exposure and withdrawal may not significantly after the function of glycinergic
      inhibitory neurotransmission and that the ethanol withdrawal syndrome is
      indicative of alterations in specific neuronal mechanisms rather than of a
      generalized state of central nervous system hyperexcitability.

PMID- 8279663
TI  - Ethanol-induced modulation of cytokine production by splenocytes during murine
      retrovirus infection causing murine AIDS.
AB  - Ethanol (ETOH) consumption has been associated with general suppression of the
      immune response, resulting in increased susceptibility to infection. Chronic
      dietary ETOH consumption may be one of the cofactors accelerating development of
      human acquired immune deficiency syndrome (AIDS) after retrovirus infection.
      Chronic dietary ETOH [5% (v/v)] in the Lieber-DeCarli liquid diet was fed female
      C57BL/6 mice inoculated with LP-BM5 retrovirus causing murine AIDS for 11 weeks.
      Because cytokines are key regulators of humoral and cellular immunity, their
      production by concanavalin A (ConA) and lipopolysaccharide (LPS)-induced
      splenocytes was measured by ELISA methods. Decreased levels of interleukin (IL)-2
      caused by retrovirus infection remained unchanged. Elevated levels of IL-5 and IL
      6 produced in vitro by ConA-stimulated spleen cells during retrovirus infection
      were significantly further increased by dietary ETOH. Elevated IL-4 due to
      retroviral infection were not affected by dietary ETOH. Increased production of
      IL-10 induced by retrovirus infection, however, was significantly reduced by
      dietary ETOH, whereas decreased release of interferon-tau induced by retrovirus
      infection was significantly enhanced. Elevated levels of tumor necrosis factor
      alpha produced by LPS-stimulated splenocytes from retrovirus infected mice were
      significantly further increased by dietary ETOH, whereas levels of IL-6 by LPS
      stimulated splenocytes were not affected. Suppressed T-cell proliferation caused
      by retrovirus infection was significantly reduced further by dietary ETOH.
      However, no effect of dietary ETOH was observed on decreased B-cell proliferation
      by retrovirus infection. These results suggest that dietary ETOH aggravates
      progression of immune dysfunction leading to AIDS, because dietary ETOH modifies
      production of immunological regulatory cytokines.

PMID- 8279664
TI  - A small dose of morphine leads rats to drink more alcohol and achieve higher
      blood alcohol concentrations.
AB  - Male Sprague-Dawley rats were maintained on a daily regimen of 22 hr of fluid
      deprivation followed by a 2-hr opportunity to take a sweetened alcoholic beverage
      and water for over 6 months. During the week before the formal procedures of the
      experiment described herein, access to the alcoholic beverage was limited to 1.5
      hr, but access to water was still for 2 hr. Intakes of ethanol, in terms of g/kg,
      were tabulated at 30 min for half of the rats and at 90 min for the rest. On the
      day of formal procedures, half of the rats of the 30- and 90-min measures were
      given 1 mg/kg of morphine sulfate just before the drinking session, whereas the
      rest received physiological saline. Morphine increased mean g/kg intakes of
      ethanol, as compared with controls, at 30 and 90 min. Blood alcohol levels were
      also increased. These data suggest that the well-documented ability of small
      doses of morphine to increase rats' intake of ethanol is probably not related to
      its ability to produce gastrointestinal effects, but rather due to its ability to
      modulate central motivational mechanisms associated with ingestion.

PMID- 8279665
TI  - In vivo effect of chronic ethanol consumption on the fatty acid composition of
      phosphatidylinositols in resting and anti-CD3-activated lymphocytes.
AB  - Fatty acid composition of phosphatidylinositols was analyzed in peripheral blood
      lymphocytes from nine alcoholic patients who were well nourished and without
      severe acute and chronic liver disease, before and after stimulation with anti
      CD3 antibody. Six comparable nondrinkers were studied as controls. A reduction in
      unsaturated fatty acid (mainly arachidonic) and an increase in palmitic and
      stearic acid molar content were observed in phosphatidylinositol (PI),
      phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate
      (PIP2) in unstimulated samples from alcoholic patients in comparison with normal
      subjects, leading to a significant decrease in the saturated/unsaturated ratio.
      In controls, anti-CD3 stimulation caused a marked decrease in arachidonic acid
      relative molar content counterbalanced by an increase in other polyunsaturated
      fatty acid relative molar content in PI, PIP, and PIP2 fractions. Interestingly,
      after anti-CD3 stimulation, alcoholic patients show the same trend of
      modification in the fatty acid composition resulting in a sharp reduction of
      arachidonic acid relative molar content. These results support the hypothesis of
      an alteration in nutrients being responsible for immune derangement in
      alcoholics.

PMID- 8279666
TI  - Reduction of ethanol intake by aerosol inhalation of a beta-adrenergic agonist:
      new route--new treatment approach?
AB  - The quick, convenient, unobtrusive administration of a low dose of a drug that
      effectively reduces alcohol intake could be a useful adjunct to any program that
      aims to treat alcohol abuse. This study evaluates the ability of isoproterenol, a
      drug that has previously been shown to reduce ethanol intake, to exercise this
      action when administered as a metered aerosol mist. Rats were trained to self
      administer ethanol using a procedure that limits access to a brief daily
      availability period. Once intake stabilized, animals were given isoproterenol by
      metered aerosol inhalation just before ethanol availability. A custom-designed
      helmet attached to a commercially available mistometer was used to deliver the
      drug. Isoproterenol produced a dose-dependent reduction in ethanol intake and an
      increase in water intake replicating the effects of parenterally administered
      isoproterenol on ethanol and water consumption. These findings demonstrate that
      the administration of isoproterenol in inhaled aerosol form can effectively
      reduce voluntary ethanol consumption in rats. The administration of
      pharmacologically active antialcohol agents via the inhalation route may be
      useful in the symptomatic treatment of alcohol abuse in humans.

PMID- 8279667
TI  - Effects of alcohol administration on the disinhibition of racial prejudice.
AB  - Eighty-two white male undergraduate social drinkers were selected from high and
      low scorers on the Modern Racism Scale. Subjects were randomly assigned to 1 of 3
      balanced placebo design conditions. After consuming their beverages, subjects
      viewed a videotape interaction between a Black and a White confederate. The
      subjects were told to rate the behaviors of the confederates, including an
      ambiguous shove of the White confederate by the Black confederate. It was
      expected, according to attribution theory, that high racism subjects would label
      the shove as more aggressive when they believed they had consumed alcohol,
      because alcohol could be used as an excuse for the socially unacceptable behavior
      of racial discrimination. A mood measure was also administered. Significant main
      effects of racism group and alcohol dosing were found for seriousness of
      aggression ratings, with high racism subjects and those expecting alcohol
      reporting more serious aggression, but the racism group by dosing condition
      interaction was not significant. A significant racism group by dosing condition
      interaction was found for the tension/anxiety mood scale, with greater tension
      being reported by high racism subjects who received alcohol. The results were
      related to theories of alcohol's disinhibiting and attention-limiting properties.

PMID- 8279668
TI  - Magnetic resonance spectroscopic imaging of ethanol in the human brain: a
      feasibility study.
AB  - The in vivo distribution of ethanol in normal human brain following the
      consumption of a moderate amount of alcohol was measured using magnetic resonance
      spectroscopic imaging. Three subjects were studied, and the spatial distribution
      of brain ethanol, 60-min postingestion and measured at a spatial resolution of
      1.5 cm, was found to be highly nonuniform with the relative ethanol signal in
      cerebral spinal fluid, gray matter, and white matter determined to be 1.00, 0.72,
      and 0.37, respectively. These spectroscopic imaging results indicate that whereas
      in vivo magnetic resonance studies of ethanol are feasible, quantitative studies
      of alcohol need to account carefully for the various tissue types within the
      observed volume.

PMID- 8279669
TI  - End-of-treatment self-efficacy, aftercare, and drinking outcomes of alcoholic
      men.
AB  - In substance abusers, low end-of-treatment self-efficacy is thought to be a
      predictor of increased vulnerability of relapse following treatment. This study
      is an evaluation of relationships between end-of-treatment self-efficacy,
      aftercare, and drinking outcomes in a subsample of male alcoholics participating
      in a treatment outcome study. After completing Behavioral Marital Therapy (BMT),
      the alcoholics and their spouses were randomly assigned to either an aftercare or
      a no additional treatment condition and followed up for 1 year. In subjects who
      received no additional treatment, low self-efficacy at the end of BMT predicted
      poorer drinking outcomes, even after drinking behavior during BMT was controlled
      for. For subjects in the aftercare condition, self-efficacy at the end of BMT did
      not predict drinking outcomes. Explanations for the results, as well as
      implications for models of relapse, are discussed.

PMID- 8279670
TI  - Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to
      the Wernicke-Korsakoff syndrome.
AB  - Chronic alcoholism results in thiamine deficiency as a consequence of poor
      nutrition, impaired absorption, and decreased phosphorylation to the enzyme
      cofactor form of the vitamin, thiamine pyrophosphate (TPP). Results of this study
      demonstrate significant reductions of TPP-dependent enzymes [pyruvate
      dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH), and
      transketolase] in autopsied cerebellar vermis samples from alcoholic patients
      with the clinical and neuropathologically confirmed diagnosis of Wernicke
      Korsakoff Syndrome (WKS). Enzyme activities in brain samples from alcoholics
      without WKS were within normal limits and activities of a nonthiamine-dependent
      enzyme, glutamate dehydrogenase, were not significantly different from control
      values in brain samples from alcoholics with or without WKS. These findings
      provide evidence, for the first time, of a direct implication of TPP-related
      metabolic processes in the pathogenesis of WKS. Decreased activities of alpha
      KGDH could be the trigger for a sequence of metabolic events resulting in energy
      compromise, and ultimately neuronal death in this syndrome.

PMID- 8279671
TI  - Protective effect of Liv.52 on alcohol-induced fetotoxicity.
AB  - The adverse effects of maternal alcohol consumption on the development of the
      fetus are well known. The adverse effects of ethanol on the liver are now
      believed to be due to acetaldehyde formed as an intermediate metabolite of
      ethanol. Liv.52 has been shown to bring about faster elimination of acetaldehyde
      from the body and thus prevent alcoholic liver damage. Other toxic effects of
      alcohol may also be due to acetaldehyde and may be prevented by Liv.52. In this
      study, rats were given 20% (v/v) ethanol in drinking water, during the gestation
      period, and the effect on maternal body weight and fetal outcome was noted. The
      protective effect of Liv.52 administration during the gestation period was
      studied. The results show that ethanol ingestion caused a decrease in gestational
      weight gain, total fetal weight, and number of live fetuses. There were increases
      in resorptions. Liv.52 administration reduced the deleterious effects of ethanol.
      The concentration of acetaldehyde in the amniotic fluid of ethanol-consuming
      animals was 0.727 microgram/ml. Liv.52 administration lowered it to 0.244
      microgram/ml. The protective effect of Liv.52 could be due to the rapid
      elimination of acetaldehyde.

PMID- 8279672
TI  - ICD-10 and proposed DSM-IV harmful use of alcohol/alcohol abuse and dependence,
      United States 1988: a nosological comparison.
AB  - The purpose of this study was to compare ICD-10 and the proposed DSM-IV (options
      1 and 2) diagnostic criteria for harmful use/abuse and dependence in a
      representative sample of the United States general population. Harmful use/abuse
      and dependence categories were contrasted in terms of prevalence and overlap. The
      prevalences of DSM-IV diagnoses of alcohol abuse and dependence combined were
      much greater than those for the corresponding ICD-10 diagnoses. Disaggregation of
      the harmful use/abuse and dependence diagnoses showed that the major discrepancy
      between the classification systems resided between harmful use and abuse
      categories. The prevalence of the harmful use of alcohol was nearly nonexistent
      in this general population sample. Reasons for this and other discrepancies are
      discussed in terms of the hypothesized severity of the harmful use criteria,
      differences in the number of diagnostic criteria and the content of the ICD-10
      and DSM-IV dependence categories, the relationship between the harmful use/abuse
      and dependence categories, and the impact of the duration criterion.

PMID- 8279673
TI  - Liver transplantation for alcoholic liver disease: survival of patients
      transplanted with alcoholic hepatitis plus cirrhosis as compared with those with
      cirrhosis alone.
AB  - From January 1986 through December 1991, a total of 221 patients with alcoholic
      liver disease received liver transplantation. In 147 of these cases, complete
      pretransplant histopathologic, demographic, and laboratory data (minimum of CBC,
      AST, ALT, total bilirubin, albumin, and prothrombin time) were available for
      review. Forty-five (30%) of the 147 recipients had alcoholic hepatitis plus
      cirrhosis (AH), whereas 70% had cirrhosis (CIRR) alone. Age and sex were similar
      in the subgroups, but the patients with CIRR had a greater AST/ALT ratio, longer
      protime, and lower platelet count (all p < 0.01). Coexistent hepatitis B (4.7%)
      or hepatitis C (4.1%) was similar in both groups. Current survival is 80% for
      patients with AH and 84% for those with CIRR (NS). Overall, survivors were
      younger (43.4 +/- 1.7 years) than nonsurvivors (53.6 +/- 3.2) (p < 0.01), an age
      influence that was significant in the CIRR group (p < 0.01) but not in the AH
      group. Inexplicably, the AST/ALT ratio was greater in AH survivors (1.5 +/- 0.2)
      than it was in nonsurvivors (0.4 +/- 0.1) (p < 0.01). In patients with CIRR, the
      platelet count was greater in survivors (252 +/- 29 vs. 86 +/- 11 x 10(9)
      cells/liter). The data support the clinical impression that patients with chronic
      decompensated cirrhosis referred for liver transplantation had more severe
      complications of their liver disease than did those with AH. Survival in both
      subgroups was similar, but overall the survivors are nearly a decade younger than
      the nonsurvivors.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279674
TI  - Improved separation of acetaldehyde-induced hemoglobin.
AB  - A fast-eluting minor variant of hemoglobin A, designated as HbA1-AcH, appears
      elevated after the incubation of red blood cell hemolysates with acetaldehyde
      (AcH) and has been proposed as a diagnostic marker for alcoholism or as an
      indicator for heavy drinking. We have developed an improved HPLC separation of
      this peak and others elevated by AcH using a polyaspartic acid column (PolyCAT A,
      PolyLC, Inc.) and a nonlinear buffer gradient with pH changes from 6.6 to 6.8.
      Saline-washed red blood cells were treated with sodium acetate buffer (pH 5.5) to
      remove unstable Schiff bases, and then hemolyzed by addition of an equal volume
      of H2O and 0.4 volumes of CCI4. HbA1-AcH and several others, including two peaks
      in the HbA1a+b cluster, Hb Pre-A1c, and HbA1d3 were significantly increased by
      AcH incubation, and the changes were only partially reversible with time.
      Improved resolution of these peaks allows more accurate quantitation of AcH
      adducts of hemoglobin.

PMID- 8279675
TI  - Alcohol consumption and alcoholic liver disease: evidence of a threshold level of
      effects of ethanol.
AB  - The effects of long-term moderate or "social" alcohol consumption (10-80 g daily
      intake) on the incidence of features of alcoholic liver disease (ALD) were
      delineated in a consecutive autopsy series of 210 males. The subjects' daily
      intake, as well as duration of alcohol consumption, was determined by an
      interview with the spouse or a close acquaintance and compared with
      semiquantitative histological scores for stage of ALD. No significant increase in
      the incidence of features of ALD could be related to all-year daily intake of
      ethanol below 40 g (40 g equals 1.1 liter of beer, 0.44 liter of wine, and 0.11
      liter of spirits). However, daily intake between 40-80 g increased relative liver
      weight on average 3.1 g/kg of body weight (p < 0.02), the frequency of fatty
      liver from 11.7 to 47.2% [relative risk (RR) = 4.4], and the frequency of mainly
      slight alcoholic hepatitis up to 16.7% (RR = 7.5). The incidence of both bridging
      fibrosis and liver cirrhosis increased significantly (RR = 8.8) only when daily
      intake exceeded 80 g. Amounts of ethanol exceeding 80 g did not relate to further
      increases in incidence of bridging fibrosis or liver cirrhosis. These findings
      suggest that, in males, daily ingestion of ethanol below 40 g for a period of 25
      years does not increase the risk of alcohol-related liver disease.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279676
TI  - Effects of alcohol, carbon tetrachloride, and choline deficiency on iron
      metabolism in the rat.
AB  - The effects of alcohol on hepatic iron uptake and intestinal iron transport were
      studied in rats fed a nutritionally replete liquid diet containing varying
      quantities of ethanol. Results were compared with those from animals exposed to
      carbon tetrachloride (CCl4) to produce hepatocellular necrosis or a choline
      deficient diet to produce steatosis and cirrhosis. A high ethanol intake for 4 or
      10 weeks produced hepatic steatosis. CCl4 produced hepatocellular necrosis.
      Choline deficiency was associated with steatosis +/- cirrhosis. Intestinal iron
      transport was unaffected by ethanol, CCl4, or choline deficiency. Hepatic iron
      uptake was significantly depressed in rats consuming 11.7 g/kg/day ethanol (p <
      0.01) for 4 weeks. Choline-deficient animals studied at 14 weeks also had
      significantly decreased hepatic iron uptake (p < 0.01); results were similar in
      the cirrhotic and noncirrhotic animals. Conversely, CCl4 exposure produced a
      significant 5-fold increase in hepatic iron uptake (p < 0.001). Results suggest
      that ethanol consumption, fatty liver, and cirrhosis are not responsible for any
      increase in iron absorption or of hepatic iron uptake in the rat model. Acute
      hepatocellular injury is followed by increased hepatic iron uptake.

PMID- 8279677
TI  - Low-level hyperbaric antagonism of ethanol-induced locomotor depression in
      C57BL/6J mice: dose response.
AB  - This study characterized the antagonistic effects of hyperbaric exposure on the
      dose-response curve for ethanol-induced depression of locomotor activity. Drug
      naive, male C57BL/6 mice were injected intraperitoneally with saline, 1.5, 2.0,
      2.5, or 3.0 g/kg ethanol, and were exposed to 1 atmosphere absolute (ATA) air or
      12 ATA helium-oxygen gas mixtures (heliox) at temperatures that offset the
      hypothermic effects of ethanol and helium. Locomotor activity was measured 10-30
      min after injection. In addition, the effects of exposure to 12 ATA heliox on
      blood ethanol concentrations were tested in a separate group of mice injected
      with 2.5 g/kg ethanol. Ethanol produced a dose-dependent depression of locomotor
      activity beginning at 2.0 g/kg. Exposure to 12 ATA heliox completely antagonized
      the locomotor depressant effects of 2.0 and 2.5 g/kg ethanol and partially
      blocked the effects of 3.0 g/kg. Activity in mice given 1.5 g/kg ethanol was not
      significantly affected at 1 ATA air, but was significantly increased at 12 ATA
      heliox. Low-level hyperbaric exposure shifted the ethanol dose-response curve to
      the right with a resultant increase in the ED50 of ethanol for locomotor
      depression from 2.6 to 3.3 g/kg. Exposure to 12 ATA heliox did not alter blood
      ethanol concentrations in mice injected with 2.5 g/kg ethanol. These findings
      with 12 ATA heliox present key new evidence for the hypothesis that low-level
      hyperbaric exposure acts directly, with a pattern analogous to a competitive,
      mechanistic antagonist of ethanol.

PMID- 8279678
TI  - Prenatal alcohol exposure blunts interleukin-1-induced ACTH and beta-endorphin
      secretion by immature rats.
AB  - The functional relationship between the immune and the hypothalamic-pituitary
      adrenal (HPA) axis [and in particular the release of pro-opiomelanocortin (POMC)
      related peptides and corticosteroids induced by interleukins (ILs)] is essential
      for coordinating the appropriate immune responses to pathogens. Exposure of
      pregnant mammalian females to alcohol results in abnormal immune functions in the
      offspring, as well as in altered HPA axis activity. We therefore tested the
      hypothesis that prenatal alcohol exposure might modify the stimulatory action of
      ILs on the HPA axis of the pups, thus providing a mechanisms through which this
      treatment results in increased rate of infectious or inflammatory processes.
      Pregnant dams were fed a liquid alcohol diet throughout gestation. Dams with free
      access to food (ad libitum group), or dams fed an isocaloric diet in which
      sucrose replaced alcohol (pair-feeding), were also included. At 22-24 days of
      age, the pups were injected intraperitoneally with IL-1 beta, corticotropin
      releasing factor (CRF), or the vehicle. Blood samples obtained 1-2 hr later
      indicated that the alcohol diet resulted in significantly blunted
      adrenocorticotropic hormone (ACTH) and beta-endorphin, but not corticosterone
      release, in response to IL-1 beta. Pair-fed pups also showed some decrease in
      their pituitary response, although to a lesser degree. In contrast, there was no
      measurable difference in the ability of CRF to increase plasma ACTH levels. These
      results suggest that prenatal exposure to alcohol interferes with the stimulatory
      action of IL-1 beta on the secretion of POMC-related peptides, a phenomenon
      probably not caused by decreased pituitary responsiveness to CRF.(ABSTRACT
      TRUNCATED AT 250 WORDS)

PMID- 8279679
TI  - Acute interactions between cytokines and alcohol on ACTH and corticosterone
      secretion in the rat.
AB  - Possible interactions between alcohol (EtOH) and interleukins (ILs) were studied
      in intact and adrenalectomized (ADX) rats. In intact animals, administration of
      0.3 or 0.65 g EtOH/kg 30 min to 4 hr earlier did not cause measurable changes in
      plasma adrenocorticotropic hormone (ACTH) levels measured immediately before
      acute intravenous injection of IL-1 beta or endotoxin [lipopolysaccharide (LPS)],
      and did not interfere with the ability of either treatments to increase ACTH
      secretion. Administration of 1.5 g EtOH/kg, on the other hand, resulted in
      elevated plasma ACTH and corticosterone 30 min later, and significantly decreased
      the magnitude of the ACTH response to IL-1 beta in both intact and ADX rats. When
      administered 4 hr before the cytokine, however, 1.5 g EtOH/kg did not alter the
      responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to IL-1 beta.
      Studies of the reverse paradigm were conducted in rats injected with LPS, a means
      of increasing endogenous IL-1 levels. Intraperitoneal administration of alcohol 4
      hr later resulted in measurably blunted ACTH release by intact rats, but not ADX
      animals. We conclude that when prior alcohol administration does not result in
      elevated ACTH levels at the time of IL-1 injection, no alteration in the HPA
      axis' response to the cytokine is observed. As we have shown in other experiments
      that circulating levels of corticosterone were temporarily increased by all doses
      of alcohol used in the present study, these results suggest that steroid feedback
      did not play a major role in modulating the ability of IL-1 beta to activate the
      HPA axis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279680
TI  - Captopril and hydrochlorothiazide (Capozide) combine to enhance the reduction in
      voluntary alcohol intake in rats.
AB  - The effect of Capozide, the combination of captopril with a hydrochlorothiazide
      diuretic, on voluntary alcohol intake was assessed in two experiments. In
      experiment 1 naive rats who were maintained on ad libitum food and water were
      given daily 40-min access to a 6% (w/v) alcohol solution and water. Daily
      intraperitoneal injections of captopril (10 mg/kg) reduced alcohol intake, but
      the combination of captopril (5 and 10 mg/kg) and hydrochlorothiazide (2.5, 5,
      and 10 mg/kg) enhanced the reduction in intake. In experiment 2, captopril alone,
      hydrochlorothiazide alone, and the combination of captopril and
      hydrochlorothiazide were again administered daily in the limited access
      procedure. Captopril (10 mg/kg) again reduced alcohol intake as did all three
      doses of hydrochlorothiazide (2.5, 5, and 10 mg/kg). Compared with the individual
      effects of captopril and hydrochlorothiazide, Capozide exerted a supra-additive
      reduction in alcohol intake. These effects were not due to drug-induced changes
      in the pharmacokinetics of alcohol. Taken together these results demonstrate an
      enhanced potency of Capozide in suppressing alcohol intake and invite their
      testing in a population of hypertensive alcoholics and alcohol abusers.

PMID- 8279681
TI  - Effects of levamisole on ethanol-induced suppression of lactational immune
      transfer in rats.
AB  - Maternal ethanol consumption in rats has been shown to inhibit lactational
      transfer of immunity to Trichinella spiralis (T. spiralis) from dams to their
      neonates. The purpose of this study was to determine if this depressed immune
      transfer could be altered by treating the dams with a known immunostimulatory
      drug during pregnancy and lactation. Groups of female rats were fed ethanol
      containing or were pair-fed isocaloric control liquid diets for 30 days, infected
      orally with 1,000 T. spiralis larva, and then continued on diet for 10 days to
      allow the adult worms to establish. The animals were placed on chow diets
      (maximum 5 days) and mated 1 to 1 with males. On day 1 of pregnancy the animals
      were returned to their respective liquid diets through pregnancy and lactation.
      One-half of the ethanol-treated animals was given 15 mg/kg body weight of
      levamisole in the diet beginning on day 10 of pregnancy and continuing until day
      17 of lactation. On day 19 of lactation, pups from all experimental groups were
      challenged orally with 200 T. spiralis larva, and killed at 3 or 8 days
      postchallenge. Assays for intestinal worm burdens, IgG anti-T. spiralis serum
      antibodies, and mesenteric lymph node cell proliferation were conducted. At both
      sacrifice periods, pups from ethanol-treated animals showed significantly higher
      intestinal worm counts (decreased immunity) and significantly lower titers of
      specific antibodies than the pups of pair-fed animals or pups of animals
      receiving levamisole in addition to ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279682
TI  - Diminution of biological reactivity of ethanol by changing the solution structure
      by weak ultrasonication.
AB  - The weak ultrasonication (40 kHz, 12 mW, 1 week) of ethanol solutions was found
      to reduce stimulation of the senses of smell and taste by the ethanol on the
      basis of blind tests with an aqueous ethanol solution (33.0% w/v) and an immature
      distilled spirit (25.0% v/v). Experiments on mice also demonstrated that a
      treated aqueous ethanol solution had a weaker depressant effect on the central
      nervous system, as evaluated by the relative frequency with which mice regained
      the righting reflex at a dose of either 4.0 or 4.5 g/kg (p < 0.05 or p < 0.01,
      respectively) and by the reduction in rectal temperature at a dose of 5.0 g/kg (p
      < 0.05) soon after ethanol administration. Analyses of both the ethanol
      concentration by head-space gas chromatography and the free radicals by electron
      spin resonance spectrometer failed to reveal any chemical changes in aqueous
      ethanol solutions subjected to weak ultrasonication. However, measurement of the
      spin-lattice relaxation time (T1) of the 2H of water molecules by 2H-NMR showed
      that the treatment slightly accelerated the thermal motion of water molecules in
      the solutions. Treated solutions were also found to have a slightly higher
      density than untreated ones. These physical data demonstrate that weak
      ultrasonication induces a structural change, such as a more compact and
      homogeneous structure by changing the microdynamic behavior of the solution.
      These biological and physical studies suggest that only a slight structural
      change in an ethanol solution induces a marked change in the biological
      reactivity of ethanol without any chemical modification of the solution itself.

PMID- 8279683
TI  - Sex differences in ethanol-induced dopamine release in nucleus accumbens and in
      ethanol consumption in rats.
AB  - In vivo microdialysis was used to examine changes in nucleus accumbens and
      striatal dopamine, dihydrophenylacetic acid (DOPAC), and homovanillic acid (HVA)
      following acute administration of ethanol (0.0, 0.25, 0.5, 1.0, or 2.0 g/kg) in
      male and female Long-Evans rats. Following dialysis, rats were trained to bar
      press for oral ethanol reinforcement. In nucleus accumbens, females showed
      significant increases in extracellular dopamine following 0.25 or 0.5 g/kg
      ethanol, but did not show significant increases over baseline at the higher
      doses. Males showed slight increases in dopamine at the lower doses and decreased
      dopamine at 2.0 g/kg. In striatum, both sexes showed increased dopamine at the
      lower doses and decreased dopamine at 2.0 g/kg. There were slight increases in
      nucleus accumbens DOPAC and HVA at some doses in both sexes, but no changes in
      striatal metabolite levels. In addition to showing increased responsiveness to
      ethanol-induced mesolimbic dopamine stimulation, females consumed more ethanol
      than males during behavioral testing. The pattern of both greater ethanol-induced
      nucleus accumbens dopamine release and greater ethanol consumption in females
      supports the hypothesis that ethanol reward is mediated, at least in part, by the
      mesolimbic dopamine system.

PMID- 8279684
TI  - Prenatal ethanol exposure alters ethanol-induced dopamine release in nucleus
      accumbens and striatum in male and female rats.
AB  - Using in vivo microdialysis, ethanol-induced dopamine release in nucleus
      accumbens and striatum was examined in adult male and female Long-Evans rats
      exposed prenatally to ethanol and in controls. Following dialysis, ethanol intake
      was measured in an operant paradigm. Control rats showed increased dopamine
      release in nucleus accumbens and striatum in response to 0.5 g/kg ethanol, but
      not to 1.0 g/kg. Fetal ethanol-exposed rats showed no dopamine response at 0.5
      g/kg. At 1.0 g/kg, fetal ethanol-exposed males showed increased dopamine release
      in both structures. Prenatally exposed females showed no change in accumbens, and
      decreased release in striatum. Fetal ethanol exposure did not significantly
      influence ethanol intake. The findings suggest that prenatal ethanol exposure
      influences subsequent neurochemical responses to ethanol; however, how these
      neurochemical measures are related to ethanol intake could not be determined in
      the present study. Data are discussed in terms of sex-specific shifts in the dose
      response function for ethanol-induced dopamine release resulting from prenatal
      ethanol exposure.

PMID- 8279685
TI  - In vivo effects of disulfiram and cyanamide on canine liver aldehyde
      dehydrogenase isoenzymes as detected by high-performance (pressure) liquid
      chromatography.
AB  - Methods for analysis of aldehyde dehydrogenase isoenzymes using high-performance
      (pressure) liquid chromatography (HPLC) were used to determine in vivo effects of
      disulfiram and cyanamide on canine liver aldehyde dehydrogenase (ALDH)
      isoenzymes. Liver ALDH isoenzymes from control and disulfiram- or cyanamide
      treated dogs were separated by ion-exchange HPLC, and enzyme activity was
      detected using a postcolumn reactor. Two major peaks of ALDH activity (peaks I
      and II) were detected. Varying the composition of the reaction column reagents
      resulted in alterations in the elution profiles consistent with the kinetic
      properties of individual isoenzymes (i.e., ALDH IB in peak I and ALDH IIB in peak
      II), including estimates of the Km for acetaldehyde and the effects of magnesium
      ions on ALDH activity. Disulfiram treatment decreased both peaks depending on
      disulfiram dose and length of treatment, with peak I being more sensitive to
      inactivation than peak II. Reagents containing MgCl2 (1 mM) decreased peak I and
      increased peak II compared with EDTA (1 mM) for samples from both control and
      disulfiram-treated animals. These data are consistent with the assignment of the
      disulfiram-sensitive isoenzyme (ALDH IB) to peak I and the isoenzyme stimulated
      by magnesium ions (ALDH IIB) to peak II. In vivo cyanamide treatment produced
      similar decreases in both peaks to a maximum decrease of approximately 30% of
      control depending on cyanamide dose. Peak I, however, was more sensitive than
      peak II to in vitro inactivation by cyanamide, which suggests that cytosolic ALDH
      in the dog (in contrast to other mammals) is more sensitive to inactivation than
      mitochondrial ALDH.

PMID- 8279686
TI  - Teratogenic effects of ethanol during hyperplastic growth in cardiac myocyte
      cultures.
AB  - Ethanol alters cellular growth and maturation, teratologic factors that are
      recognized as contributing to abnormal phenotypic expression. Cultured neonatal
      Sprague-Dawley rat cardiac myocytes were utilized to determine how ethanol alters
      growth and development. Two ethanol exposure paradigms were studied: (1)
      constant, to cultures in closed chambers for 7 days at low (10 mM) and high (50
      mM) concentrations; and (2) periodic (24-hr) to cells during hyperplastic growth.
      In constantly exposed cultures, 10 and 50 mM ethanol concentrations depressed the
      rate of leucine incorporation and the rate of thymidine uptake during early
      hyperplastic growth (log phase growth). A resultant slower expansion of cell
      populations was noted. Although the period of maximum vulnerability appeared to
      be the hyperplastic growth phase, a second set of experiments using 10 and 50 mM
      ethanol were performed to assess the effects of short (24-hr) exposures. DNA
      synthesis was depressed during early hyperplastic growth compared with controls
      (days 2-4), reflected as a decrease in thymidine incorporation and smaller cell
      population. This study demonstrates that ethanol depresses both DNA and protein
      synthesis during hyperplastic growth resulting in an insufficient, protein
      deficient cell mass, incapable of participating in normal embryogenesis.

PMID- 8279687
TI  - Ethanol-induced changes in astrocyte gene expression during rat central nervous
      system development.
AB  - Disruption of spatial and temporal patterns of gene expression in cells of the
      developing brain could result in abnormal development. We report that briefly
      exposing neonatal rats to a moderate dose of ethanol on postnatal days 5 through
      7 caused a large, specific increase in glial fibrillary acidic protein (GFAP)
      mRNA and GFAP. Astrocytes of the cerebral cortex were apparently more sensitive
      to this effect of ethanol than astrocytes in several other brain regions. As a
      first step in the characterization of an vitro model of ethanol's effect on GFAP
      gene expression, ethanol was added to the media of primary cultures of cortical
      astrocytes in a pattern of exposure and at concentrations equal to pups' peak
      blood levels. This resulted in an increase in GFAP mRNA whose magnitude and
      specificity mirrored that observed in the animal model. Together, these results
      suggest that even brief exposure to ethanol can alter gene expression in
      astrocytes, and forms the foundation for further characterization of an in vitro
      model that may be used to determine the mechanism of this effect.

PMID- 8279688
TI  - [Rocuronium, the "ideal" nondepolarizing muscle relaxant?].
AB  - Rocuronium bromide (Org 9426) is a new, non-depolarising steroidal muscle
      relaxant that is currently undergoing extensive clinical trials worldwide. Since
      it is expected to be introduced into clinical practice in the near future, the
      purpose of this review is to give a summary of the currently available
      information on this promising new compound. The search for the so-called ideal
      muscle relaxant [34] in the last years was focused on a non-depolarising compound
      that could replace succinylcholine for rapid intubation. The currently most
      frequently used agents vecuronium and atracurium have an onset of action that
      usually does not allow intubation earlier than 3 min after its injection. Recent
      animal [40] and human [10] studies have shown that development of neuromuscular
      blockade of the vocal cords and laryngeal muscles can be faster than that of the
      peripheral skeletal muscles. This would mean that intubation can be performed
      before complete relaxation of the adductor muscle of the thumb is achieved.
      Rocuronium is the 2-morpholino, 16 N-allyl-pyrrolidino derivative of the 3
      hydroxy metabolite of vecuronium. In initial clinical studies [13, 42] its most
      impressive features appeared to be rapid onset time and, more importantly, the
      rapid development of good intubating conditions. Thirty to 90 s after the
      injection of 0.6 mg/kg (2 x ED90), rocuronium provided intubating conditions that
      were equal to those observed after succinylcholine [9, 17, 31, 38]. Although the
      onset time of rocuronium at the adductor pollicis muscle is slower than that of
      succinylcholine, intubation with this compound can be performed faster than with
      any other non-depolarising agent.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279689
TI  - [Propofol versus diazepam. Sedation in ophthalmologic surgery under local
      anesthesia].
AB  - This prospective study was designed to evaluate the sedative effect of two
      different anaesthetic drugs in patients undergoing ophthalmic surgery. Propofol
      is an intravenous hypnotic agent with a short half-life of about 30 min. A
      constant high oxygen saturation in continuous pulse oximetry was achieved in
      previous studies using propofol for sedation. Furthermore, an IOP-lowering effect
      was proved. Propofol was compared to diazepam, a well-established sedative, which
      has been used for many years for sedation of patients in local anaesthesia.
      METHOD. One hundred patients of comparable anaesthesiologic risk (ASA classes 2
      4) undergoing identical surgical procedures received either propofol (n = 50), or
      diazepam (n = 50). Propofol was infused at a rate of 0.8-3.0 mg/kg/h, while
      diazepam was given as a slow intravenous bolus of 5 mg before surgery. All
      patients were monitored by continuous pulse oximetry. RESULTS. Oxygen saturation
      of patients receiving propofol was never less than 96%. In contrast, oxygen
      saturation of patients sedated by diazepam dropped to 85%, especially for the
      first 5 min following administration, before improving to 95% during the next 10
      min. None of the patients who received propofol showed signs of motor unrest, a
      great handicap in ophthalmic surgery, while four patients who received diazepam
      were restless enough to hamper the procedure. None of the patients who received
      propofol developed respiratory depression. In contrast, marked respiratory
      depression, motor agitation, and postoperative fatigue slowing mobilization were
      common in patients who received diazepam.

PMID- 8279690
TI  - [The circulatory effect of conduction anesthesia near the spinal cord.
      Pathogenesis, prophylaxis and therapy of heart circulation complications].
AB  - Major conduction anaesthesia is not harmless. Based on new findings about
      sympathetic blockade, it was analysed whether circulatory side effects after
      spinal or epidural anaesthesia, in particular cardiocirculatory arrest, correlate
      with the level of segmental spread and whether prophylactic or therapeutic
      measures are effective. With spinal or epidural anaesthesia in healthy,
      unpremedicated patients, blood pressure, heart rate, and cardiac output remain
      within +/- 20% of normal independent of the height of segmental spread. However,
      in patients with circulatory diseases and/or premedication blood pressure often
      drops more than 20%, especially when cranial spread exceeds T4. Cardiocirculatory
      arrest during major conduction anaesthesia: (1) is preceded by an interval of 10
      20 min recognisable by narrowing of the pulse pressure and continuous decreases
      in blood pressure and heart rate; (2) does not correlate with the level of
      segmental spread; and (3) is possibly caused by reduced filling of the heart
      and/or vagal activity. Infusion of crystalloid or colloid solutions may diminish
      the drop in blood pressure, whereas vasopressors reduce the frequency and extent
      of cardiocirculatory side effects. As yet, however, there is no safe prophylaxis
      to prevent cardiocirculatory arrest. Cardiopulmonary resuscitation after
      circulatory arrest must be combined with early administration of catecholamines.

PMID- 8279691
TI  - [30 degree trunk elevation of the patient and quality of lumbar epidural
      anesthesia. Effects of elevation in operations on the lower extremities].
AB  - The spread and intensity of lumbar epidural anaesthesia are unpredictable.
      Moreover, segments L5 and S1 are frequently missed. In this study the effect of
      30 degrees trunk elevation on the spread and intensity of lumbar epidural sensory
      and motor blockade and on the cardiovascular system were studied. METHODS. After
      oral premedication with 7.5 mg midazolam, 30 patients 20 to 40 years of age, ASA
      1-2, were randomly allocated to one of two groups according to their body
      position during injection of 20 ml 2% lidocaine (3 + 8 + 9 ml) into a lumbar
      epidural catheter (L2/3 or L3/4) and during the following 30 min: supine
      horizontal position or supine 30 degrees trunk elevation with 30 degrees leg
      elevation (hammock position). The patients received 500 ml Ringer solution before
      the epidural injection, followed by more Ringer solution. Systolic and diastolic
      blood pressures and heart rate were monitored noninvasively every 5 min; 30 min
      after the epidural injection the spread of analgesia (dullness of pinprick) and
      anaesthesia (no sensation of pinprick) as well as motor block according to
      Bromage were tested. A spread of anaesthetic segments including T12 to L3 was
      considered adequate for hip surgery, L3 to L5 for knee surgery, and L3 to S2 for
      foot surgery. Student's t-test, ANOVA, chi-square (Wilcoxon), and Mann-Whitney
      tests were used for statistical analysis. P < 0.05 was considered statistically
      significant. RESULTS. The median cephalad level of analgesia was lower in
      patients with the hammock position than those with the horizontal position (L1 vs
      T10; P < 0.05). There was no significant difference in the cranial level of
      anaesthesia (L2 vs L1) (Table 2). No significant difference was seen in the
      number of patients having adequate anaesthesia for hip surgery. Anaesthesia in
      the segments L5 and S1 was seen in 2/15 patients in the horizontal position and
      8/15 patients in the hammock position (P < 0.05). The hammock position resulted
      in a higher percentage of patients having adequate anaesthesia for knee surgery
      (60% vs 13%; P < 0.05) and foot surgery (53% vs 13%; P < 0.05) (Table 3). Motor
      block was more profound in patients in the hammock position (Table 4). Blood
      pressure and heart rate did not change significantly in patients in the
      horizontal position (Fig. 1); there was a decrease in both systolic (7 mmHg) and
      diastolic (5 mmHg) blood pressures in patients in the hammock position. Heart
      rate did not change significantly (Fig. 2). No patient needed vasopressor
      support; the body position could be maintained in all patients during the
      observation period. One or two epidural reinjections according to the spread of
      anaesthesia 30 min after the first injection and to the scheduled operation
      resulted in adequate anaesthesia in every patient. DISCUSSION. More patients in
      the hammock position developed adequate anaesthesia in the relevant segments for
      knee and foot operations than patients in the horizontal position. These included
      the frequently missed segments L5 and S1. Patients in the hammock position had a
      clinically insignificant drop in systolic and diastolic blood pressure. In
      contrast to the young and healthy patients in this study, more severe
      cardiovascular changes might result in geriatric and/or ill patients subjected to
      a hammock position. For this reason, use of the technique in geriatric and/or ill
      patients requires special attention.

PMID- 8279692
TI  - [Computer controlled brain death documentation in the intensive care unit].
AB  - An interactive, knowledge-based computer system for brain death documentation is
      presented. The specific exponents BRAINDEX R and G were realised by the software
      tool Personal Consultant Plus and the programming language Clipper, respectively.
      The strategies of conclusion were forward chaining for approximate evaluation of
      coma stages and backward chaining for analysing the brain death syndrome.
      BRAINDEX was developed for use with an IBM personal computer or compatible
      equipment. Systemic analyses were compared retrospectively with the data from
      clinical brain death protocols (n = 132) of 128 comatose patients (mean age 35.1
      +/- 15.8 years) with a Glasgow Coma Score of 3. Identical classifications (system
      vs physician) were found in all patients without diagnosis of brain death (n =
      35). Differences related to the findings of the physician were evaluated in lower
      numbers of the systemic positive diagnosis of brain death (82 vs 89) and higher
      numbers of impossibility of systemic evaluation (11 vs 2). These results were
      obtained by conclusions of the computer system drawn by restrictive systemic
      mechanisms to avoid false-negative diagnoses. The system therefore seems to be
      useful for documentation, consultation, and as a teaching instrument and data
      bank in brain death.

PMID- 8279693
TI  - [Postoperative pain therapy. The efficacy of a serotonin antagonist (GR
      38032F;ondansetron) and the prostaglandin synthesis inhibitor lysin
      acetylsalicylate (Aspisol)].
AB  - Serotonin is one of the many neurotransmitters involved in nociception. Serotonin
      antagonists may therefore reduce postoperative pain. In the present study we
      examined whether the new 5-HT3 receptor antagonist GR 38032F (ondansetron)
      reduced postoperative pain after minor surgery and compared its effectiveness
      with that of lysin acetyl salicylate (Aspisol). METHODS. A series of 100 patients
      of both sexes who were undergoing minor surgery were enrolled in this study.
      Patients who did not need analgesic medication within the first 3 h after surgery
      were regarded as "dropouts", and the rest were studied for 24 h. In a preliminary
      study (n = 19) patients received ondansetron i.v. in increasing dosages (6, 12,
      24, 48, 96 and 128 micrograms.kg-1) to evaluate the analgesic potency of this
      drug. In the main double-blind, randomized, study (n = 81), three groups were
      formed, and patients received 50 micrograms.kg-1 or 100 micrograms.kg-1
      ondansetron i.v. or saline only i.v. Analgesia was evaluated by visual analogue
      (VAS) and verbal rating scales (VRS). If pain persisted patients received 1.8 g
      lysin acetylsalicylate (LAS) i.v. RESULTS. There were 6 (out of 19) patients in
      the preliminary study and 36 (out of 81) patients in the main study who were
      dropouts; that is to say they did not require any analgesic medication within the
      first 3 h, but 12 of these dropouts needed analgesic medication more than 3 h
      after end of surgery. Pain was reduced by 82% from baseline in 7 out of 13
      patients in the preliminary study (11 men, 2 women). In the main study (n = 45,
      28 men, 17 women) 100 micrograms.kg-1 ondansetron did not show a better analgesic
      effect than 50 micrograms.kg-1, and there was no significant difference between
      ondansetron and saline. VAS showed a reduction in pain from 6.9 +/- 2.0, 6.8 +/-
      1.5 and 6.6 +/- 1.8 to 4.1 +/- 2.4, 3.4 +/- 2.2 and 3.4 +/- 2.1 in the 50
      micrograms.kg-1, 100 micrograms.kg-1 and saline groups, respectively, within 60
      min after i.v. application. VRS diminished from 2.5 +/- 0.5, 2.5 +/- 0.6 and 2.4
      +/- 0.5 to 1.7 +/- 0.7, 1.5 +/- 0.8 and 1.5 +/- 0.7, respectively. There were 26
      patients who experienced no pain relief in response to ondansetron or placebo and
      who therefore received LAS, and 21 of these then experienced significant pain
      reduction. CONCLUSION. Pain after minor surgery does not appear to be a major
      problem. For 42 out of 100 patients no analgesics were needed within the first 3
      h after end of surgery. Ondansetron was no more effective than placebo in
      reducing postoperative pain. Lysin acetylsalicylate, however, may be an effective
      alternative to opioids for the treatment of postoperative pain.

PMID- 8279694
TI  - [Right ventricular assist device (RVAD) in septic, fulminating pulmonary artery
      embolism].
AB  - We describe a 34-year-old male with pulmonary embolism. The patient had been
      admitted to a peripheral hospital for incision and drainage of a very large
      ischio-rectal abscess. Four days after successful surgical intervention and
      during a change of dressings he developed a massive pulmonary artery embolism.
      The patient was transferred to the Department of Cardiac Surgery in Graz; on
      arrival he had a cardiac arrest. Resuscitation was initiated and the patient was
      transferred to the operating theatre where emergency sternotomy and embolectomy
      revealed large thrombotic masses in the pulmonary circulation. Extracorporeal
      circulation was initiated, but despite aggressive medical measures (dopamine,
      dobutamine, isoproterenol, enoximone, and prostaglandin E1 in maximum therapeutic
      doses) and a long reperfusion time weaning was not possible. Despite the septic
      state, a right ventricular assist device (RVAD; ABIOMED BVS 5000) was installed.
      Weaning was finally accomplished with a pump flow of 2.2 l/min m2 and the patient
      transferred to the intensive care unit. On post-operative day 3 the pump flow was
      reduced to 2 l/min. The patient's condition remained stable, which made removal
      of the RVAD possible on postoperative day 5. The further course was uneventful,
      with secondary ischio-rectal wound closure. His initial psychomotor impairment
      had nearly disappeared and he was discharged 2 months later.

PMID- 8279695
TI  - [Comments on the work of H.W. Striebel et al. The role of clonidine in
      anesthesia].

PMID- 8279696
TI  - [Modern forms of artificial respiration].
AB  - Mechanical ventilation has become a widely used technique in anaesthesiology and
      intensive care medicine. Difficulties arise with patients who suffer from acute
      or chronic pulmonary disease. Lung models are used to simulate the behaviour of
      healthy and diseased lungs and to optimize breathing patterns. Flow-controlled
      ventilation is suitable for healthy lungs. Diseased lungs need more finely
      differentiated ventilatory modes that adapt to the different time constants
      within the lung. PCV seems to have some advantages in ventilation of such lungs.
      It has been demonstrated that prolongation of inspiratory time and inversion of
      the I:E ratio can open nonventilated compartments of the lung and thus reduce
      intrapulmonary shunt. BiPAP ventilation and APRV serve the same purpose.
      Additionally, they support spontaneous breathing of the patient. Weaning from the
      respirator can be achieved by either reducing the number of mandatory breaths
      (IMV, SIMV, MMV) or reducing the work of breathing by applying inspiratory
      pressure support (PSV). Both techniques can be applied simultaneously. BiPAP
      ventilation and APRV are also suitable for weaning patients from a ventilator.
      Respirators able to adapt breathing patterns to the lung mechanics of a patient
      automatically on the basis of a breath-to-breath lung function analysis (ALV) are
      currently in clinical development.

PMID- 8279697
TI  - Presence of immunoreactive atrial natriuretic peptide in nerve fibres and
      conduction cells in the conduction system of the bovine heart.
AB  - Previous findings of atrial (A-type) natriuretic peptide (ANP) in nervous tissue,
      such as the brain and the superior cervical ganglia, led us to investigate the
      possible occurrence of ANP in nervous tissue in the heart. The distribution of
      ANP in the bovine heart, particularly its conduction system, was examined by the
      use of immunohistochemical methods and an antiserum against alpha-hANP. ANP
      immunoreactivity was frequently detected in atrial myocytes and in the Purkinje
      fibres of the AV-bundle, and was sometimes seen in the Purkinje fibres of the
      bundle branches and their ramifications. On the other hand, ANP immunoreactivity
      was never seen in the conduction cells of SA- and AV-nodes. ANP immunoreactivity
      was also detected in small nerve-fibre varicosities, mainly in the AV-node and AV
      bundle. Most of these varicosities were located in the proximity of the
      conduction cells, but some occurred close to fine blood vessels or in the walls
      of arterioles. These observations show for the first time that ANP
      immunoreactivity is present not only in atrial myocytes and conduction cells but
      also in nerve-fibre varicosities in the conduction system. The observations
      suggest that ANP may act as a neuromodulator and/or neurotransmitter in the
      conduction system.

PMID- 8279698
TI  - Parvalbumin and calretinin in the avian thymus.
AB  - The avian thymic hormone, known to support the maturation of T-lymphocytes, is
      biochemically similar to parvalbumin. However, its exact cellular distribution in
      the thymus is unknown. We have therefore studied the occurrence of parvalbumin
      and other related calcium-binding proteins in this organ by immunohistochemistry
      during development and after hatching. Parvalbumin immunoreactivity appears in
      the epithelial cells on embryonic day 9, and is expressed in the cortical
      reticular cells in the adult. Calretinin is found in the clusters of medullary
      epithelial cells from embryonic day 11, whereas calbindin D-28k is absent from
      this organ. Thus, calcium binding-proteins are excellent markers for different
      compartments of the avian thymus in embryonic life and after hatching, and their
      expression seems to coincide with their functional maturation.

PMID- 8279699
TI  - Unilateral cervical vagotomy decreases the magnitude of neurogenic inflammation
      induced by capsaicin in the ipsilateral bronchial tree of rats.
AB  - Electrical stimulation of a single cervical vagus nerve produces neurogenic
      inflammation on the stimulated side of the bronchial tree, including the first
      (main) to the 4th order bronchi. In the contralateral bronchial tree, in
      contrast, only the proximal part of the main bronchus exhibits inflammatory
      changes, suggesting that vagal sensory axons present in the bronchi largely
      originate from the ipsilateral vagus nerve. Intravenous administration of
      capsaicin can evoke neurogenic inflammation in bilateral bronchial trees. Sensory
      axons from various sources are thought to be stimulated by this irritant. The
      extent to which neurogenic inflammation in both bronchial trees might be reduced
      by unilateral vagotomy is not known. In the present study, we sought to
      characterize the effect of unilateral cervical vagotomy on capsaicin-induced
      changes in plasma extravasation and secretory activity of goblet cells in the
      bronchial trees of both sides. To quantify the magnitude of neurogenic plasma
      extravasation, Evans blue was used as a tracer dye to measure
      spectrophotometrically its amount in the bronchial wall. Another tracer dye,
      Monastral blue, was used to localize the distribution of leaky blood vessels and
      to measure morphometrically their area density in the whole mounts. To
      investigate cell and tissue responses of the mucosa, histological methods were
      employed. After 2 or 4 postoperative weeks, the rats were intravenously
      administered with a single dose of capsaicin, 150 micrograms/kg. This resulted in
      different magnitudes of Evans blue extravasation in the bronchi of the two sides
      in vagotomized rats. Extravasation of Evans blue dye in the bronchial tree
      ipsilateral to vagotomy was one-half to two-thirds of that of the contralateral
      bronchial tree.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279700
TI  - Antero-posterior skeletal patterning is not dependent on continuity of the apical
      ectodermal ridge in the chick wing bud.
AB  - The mechanism of antero-posterior specification of limb skeletal pattern is still
      controversial. If, as proposed by the ZPA model, a diffusible morphogen does
      exist, its route of passage across the limb field has not been resolved. To
      investigate the contribution of the apical ectodermal ridge (AER) to the control
      of antero-posterior pattern formation, we examined the consequences of small
      wounds made to the AER. The wound response was investigated by means of resin
      histology and scanning electron microscopy; subsequent limb development and
      cartilage pattern were examined in whole-mount preparations. Although regrowth of
      the bilaminate dorsal and ventral ectoderm over the wound occurred within 15 h,
      the more highly differentiated pseudostratified columnar epithelium of the AER
      did not reform, and there was subsequent retardation of limb outgrowth at the
      wound site. At 10-11 days of development, the appearance of the limbs allowed
      them to be placed into one of three categories; presence of supernumerary
      elements, accentuation of an inter-digital cleft, or normal. The first of these
      categories included limbs in which digit 3 had bifurcated such that the sum of
      the parts of the resultant digital skeleton was greater than that which forms in
      a normal limb. Since in all of the experimental limbs all skeletal elements were
      present, we propose that continuity of the AER is not a pre-requisite for antero
      posterior skeletal pattern formation in the chick wing.

PMID- 8279701
TI  - Placental lactogen-like proteins in the rabbit placenta.
AB  - Rabbit placentae and embryos at days 11 and 12 were analyzed by two-dimensional
      gel electrophoresis and by light microscopic histology for the presence of
      placental lactogen-like proteins. Immunoblotting and immunohistochemistry were
      performed by using a goat anti-human placental lactogen serum as well as a
      monoclonal mouse anti-human prolactin immunoglobulin; the results were similar.
      In the gel electrophoresis of placental tissue, three protein spots at pH 5.6 and
      43, 39, and 35 kDa were immunostained; they were absent in the embryo.
      Immunoresponse was restricted to the cytotrophoblast. Immunofluorescent cells
      were mainly found on the proximal parts of the placental trabeculae.

PMID- 8279702
TI  - Multinucleated spermatocytes in the aging human testis: formation, morphology,
      and degenerative fate.
AB  - The ultrastructural appearance of multinucleated spermatocytes in the aging human
      testis is documented emphasizing their mode of formation and their degenerative
      fate. Multinuclearity results from confluence of cell membranes of neighbouring
      spermatocytes of one clone. Intercellular bridges are not causally involved in
      this process but are only secondarily detached from the cell membrane and,
      attaining an intracellular position, subsequently disintegrate. Accompanying or
      following the process of formation of the multinucleated spermatocytes, these
      cells undergo degeneration. There are no indications of a regular further
      development of multinucleated spermatocytes. Though quite rarely found within the
      aging human seminiferous epithelium, the appearance of these cells represents a
      germ-cell loss at the spermatocyte stage.

PMID- 8279703
TI  - Notulae seminologicae. 1. New combinations of Kartagener's syndrome.
AB  - In this note new consequences of the Kartagener's syndrome are described. In
      males the syndrome involved a diffused sperm immaturity; in one female severe
      skeletal defects were present probably resulting from bad organization of the
      renal apparatus.

PMID- 8279704
TI  - Notulae seminologicae. 2. The 'short tail' and 'stump' defect in human
      spermatozoa.
AB  - In this note several cases of stunted tails involving the total sperm population
      in sterile humans are described. Half of the cases are classified as 'short
      tailed' spermatozoa, the other half as 'stump defect' previously described in
      bulls. Both defects are referred in details at electron microscopical level.

PMID- 8279705
TI  - Enhanced quality of capacitated spermatozoa from oligoasthenozoospermic men after
      incubation in test yolk medium.
AB  - To improve artificially the quality of poor sperm samples to be used in assisted
      procreation procedures, Test Yolk Buffer (TYB) incubation effect was
      investigated. After adding the TYB procedure to the standard swim-up technique, a
      significant (P < 0.001) increase in spermatozoa velocity was observed, while the
      other seminal parameters were not affected. Three of 11 couples who had not had
      success after three intraperitoneal inseminations (IPI) with sperm prepared by
      the usual swim-up technique obtained pregnancies after IPI with TYB-incubated
      spermatozoa. These preliminary results suggest that TYB incubation for
      capacitated spermatozoa be employed in the assisted procreation strategies
      applied for male infertility.

PMID- 8279706
TI  - Kinetic activity of spermatozoa from fertile subjects and asthenozoospermic
      infertile patients.
AB  - The motility characteristics of spermatozoa from asthenozoospermic semen were
      investigated and compared to the same parameters in fertile semen. The motility
      characteristics assessed by the CellSoft semen analyser (CRYO Resources Ltd, NY)
      were the following: curvilinear velocity (VCL), straight line velocity (VSL),
      amplitude of lateral head displacement (ALH), linearity (%LIN), and beat cross
      frequency (BCF). Analysis of the data indicated a decreased kinetic activity in
      the spermatozoa from the asthenozoospermic group which is expressed as a highly
      significant decrease (P < 0.002) in the VCL and VSL compared to velocities from
      normospermic samples. Moreover, percentage linearity and ALH were also
      statistically lower (P < 0.05) in this group. However, no difference was
      evidenced for the BCF.

PMID- 8279707
TI  - Comparison between cell motion analyser, autosperm, and conventional semen
      analysis.
AB  - With the aim of explaining some of the controversy on the value of computer
      assisted methods of semen analysis, a study was conducted comparing the fully
      automated cell motion analyzer (CMA), the semi-computerized autosperm system (AS)
      and the conventional manual method. The CMA equipment gave higher values for
      sperm concentration than the mean of the three methods. Sperm concentration
      estimated with the conventional method was below the average of the three
      methods. The conventional method overestimated sperm motility, which was
      underestimated by CMA. The correlation between sperm velocity characteristics
      estimated by CMA and AS was significant, but only 18% of variability of one
      method could be explained by variability of the other. The reasons for the
      discrepancy between velocity measurements in the two methods are discussed in
      relation to possible shortcomings in sperm paths smoothing using the CMA method
      and the effect of technician training in the AS method. The AS method was found
      to provide more reproducible results which correlated better with those of the
      manual method as recommended by the World Health Organization.

PMID- 8279708
TI  - Correlation between hypo-osmotic swelling test and 'water test' to assess human
      sperm membrane integrity.
AB  - Fifty-nine men who requested vasectomy and 43 infertile patients had a semen
      analysis performed prior to surgery or during evaluation. A hypo-osmotic swelling
      test (HOS) and a new 'Water test' were performed simultaneously, in order to
      assess correlation between these two procedures. Our results showed that values
      obtained with the 'Water test' were significantly higher than those obtained with
      the HOS test (P < 0.001). These findings suggest that it is necessary to
      determine normal values for this new test before introducing it in the routine
      semen analysis.

PMID- 8279709
TI  - Synovial-type (group II) phospholipase A2 human seminal plasma.
AB  - Phospholipase A2 (PLA2) was analysed in seminal plasma of fertile, subfertile,
      and vasectomized men as well as in prostatic secretion and tissue. Immunological
      cross-reactivity was observed between synovial-type PLA2 antiserum and the enzyme
      present in seminal plasma. There was a highly significant correlation between the
      concentration of the synovial-type PLA2, as measured by a time-resolved
      fluoroimmunoassay and the catalytic activity of the PLA2. The results show that
      the PLA2 content in human seminal plasma is very high (approximately 1000 times
      of that present in blood plasma) and that the enzyme belongs to the synovial-type
      group II phospholipase A2. The results also indicate that the enzyme is secreted
      by the prostate.

PMID- 8279710
TI  - Pentoxifylline increases sperm penetration into zona-free hamster oocytes without
      increasing the acrosome reaction.
AB  - Several drugs have been used to stimulate human sperm motility, including 3-deoxy
      adenosine, caffeine, and pentoxifylline. Pentoxifylline is an inhibitor of the
      phosphodiesterase and may stimulate sperm motility by increasing the
      intracellular levels of cAMP. In this study we have evaluated the effect of
      pentoxifylline in the outcome of the sperm penetration assay into zona-free
      hamster oocytes. Twenty-seven semen samples, obtained for diagnostic purposes,
      were used. After the motile sperm were selected by the swim-up technique, the
      samples were divided into two aliquots. One aliquot was incubated with 1 mg ml-1
      of pentoxifylline at 37 degrees C, 5% CO2 for 30 min. The control aliquot was
      incubated with culture medium. The samples were then washed and resuspended in
      fresh, pentoxifylline-free medium, at a sperm concentration of 10 x 10(6) cells
      ml-1. One hundred microlitres of each sperm suspension was then deposited under
      oil and 30-40 zona-free hamster oocytes were added. After 6 h of gamete
      coincubation, the percentage of penetrated oocytes and the number of decondensed
      sperm heads were evaluated. The percentage of acrosome-reacted sperm was
      evaluated using the Pisum sativum lectin. The percentage of zona-free hamster
      oocytes penetrated was increased after pentoxifylline-treatment. The percentage
      of acrosome reacted sperm and the number of decondensed sperm heads per egg were
      not different between the control and the pentoxifylline-treated groups. The
      results suggest that the beneficial effect of pentoxifylline upon the sperm cells
      is not mediated by stimulation of the acrosome reaction.

PMID- 8279711
TI  - Effect of a nonsteroidal antiandrogen, flutamide on intraluminal acidification in
      rat testis and epididymis.
AB  - Flutamide, a pure antiandrogen was administered to intact adult male rats to
      study the effect of altered availability of hormones on in situ pH, PCO2 and
      bicarbonate concentration ([HCO3-]) of seminiferous tubules, proximal caput,
      middle caput, middle corpus, and proximal cauda epididymidis. The weights of the
      epididymis and ventral prostate as well as the plasma testosterone level showed
      antiandrogenic effects of flutamide. Relative to controls, flutamide elevated
      significantly in situ pH in proximal caput, middle caput, middle corpus and
      proximal cauda epididymidis but not in seminiferous tubules. In situ PCO2 values
      in the above segments, after flutamide, were indistinguishable from controls and
      from each other but all values remained significantly higher than systemic
      arterial blood PCO2. Flutamide treatment did not change the [HCO3-] in systemic
      arterial blood or seminiferous tubules but increased markedly the values in
      proximal caput and middle caput. The results of the present studies support the
      view that luminal acidification in the rat epididymis is under androgen control
      and may be important for sperm maturation and storage.

PMID- 8279712
TI  - Zinc arginine, a 5 alpha-reductase inhibitor, reduces rat ventral prostate weight
      and DNA without affecting testicular function.
AB  - Zinc has been implicated in steroid endocrinology of the prostate gland; and 5
      alpha-dihydrotestosterone (DHT) is believed to express androgenic responses in
      the prostate. To note the effect of neutralized zinc (zinc gluconate + arginine)
      on the prostate, 50 sexually mature rats, weighing 325 +/- 20 g, were divided
      into five groups as follows: (1) control, (2) sham, (3) castrated, and injected
      intraprostatically with (4) 10 mg neutralized zinc, and (5) 20 mg neutralized
      zinc. Results indicated significant reduction (P < 0.05) of prostate weight, 5
      alpha-reductase activity, and total protein and DNA concentrations in treated
      prostate tissue; no significant change in weight and histological structure of
      testes, epididymides, and seminal vesicles; and no significant effect on progeny
      and blood testosterone level of treated animals. These results suggest that
      direct application of neutralized zinc to the prostate offers a new modality for
      treatment of prostatitis without affecting spermatogenesis.

PMID- 8279713
TI  - Results of ofloxacin therapy in andrologic patients suffering from therapy
      requiring asymptomatic infections.
AB  - In 1990, microbiological ejaculate analyses were carried out on a routine basis
      on 125 andrological patients, in addition to the determination of the
      concentration, motility and morphology of the spermatozoa. Fourteen patients
      (11.2%) with therapy-requiring asymptomatic infections (TAI) > 10(4) CFU (colony
      forming units) ml-1 were effectively treated with Ofloxacin (Tarivid) at 2 x 200
      mg d-1 for a period of 20 d. Concentration, motility and morphology of the
      spermatozoa were determined before the Ofloxacin treatment and controlled 1, 3,
      and 6 months later and correlated to the values obtained before the treatment.
      Over the entire period of observation, the morphology did not change
      significantly, whilst initially 1 month after the treatment the concentration and
      the motility decreased significantly (P < 0.05). Three months later they again
      reached the starting values. After 6 months, a significant improvement occurred
      with regard to the motility, as compared to the starting values (P < 0.01),
      whilst the concentration remained at the level of the starting values. By this,
      Ofloxacin has been proved to be an effective medication for the treatment of TAI.
      In the end, it still remains an open question whether the improvement in sperm
      motility is primarily related to the Ofloxacin therapy.

PMID- 8279714
TI  - Prediction of the environmental fate of chemicals.
AB  - An overview is presented of the possibilities of applying multimedia
      compartmental evaluative models, and in particular the fugacity approach, to
      predict the environmental distribution and fate of organic chemicals. The use of
      this predictive approach for the evaluation of exposure to pollutants in the
      aquatic system is described, with reference to different environments or
      discharge patterns (surface and groundwaters, point and diffuse sources of
      pollution). The value and limitations of this approach are noted and the need for
      more research to improve predictive capability and practical usefulness is
      indicated. Finally some practical applications of evaluative models in the
      proposal of quantitative indices for ecotoxicological evaluation of risk from
      chemicals are described.

PMID- 8279715
TI  - Review of leaching characteristics of triazines and their degradation products.
AB  - Only few data have been published on the environmental impact of pesticide
      degradation products on soil and groundwater. It is known that some of the
      degradation products of triazines, particularly those formed from N-dealkylation
      reactions, can be phytotoxic and more mobile than their parent compounds. In some
      cases it has been shown that they are present at even higher concentrations than
      the latter. Yet, their impact on groundwater quality is unknown since information
      on both environmental levels and chemiodynamic parameters are generally lacking.
      The conclusions of this work are that many triazine degradation products may pose
      a significant hazard to the quality of groundwater and that there is a need to
      promote and extend the production of experimental data on this topic.

PMID- 8279716
TI  - Analytical problems in the quantification of elements in water bodies.
AB  - The main aspects of element analysis in natural waters are briefly surveyed.
      Particular attention is devoted to sampling, pretreatment and storage problems,
      as well as pitfalls, followed by a detailed discussion on the most flexible and
      powerful routine analytical techniques. A number of examples are also given to
      illustrate the major sectors of investigation presently being explored. Future
      trends and needs are finally outlined.

PMID- 8279717
TI  - The groundwater pollution in Lombardy (north Italy) caused by organo-halogenated
      compounds.
AB  - This paper deals with the phenomenon of the presence of organo-halogenated
      compounds in groundwaters of the Lombardy Region (North Italy). The regionwide
      study evidentiated the magnitude of the phenomenon, since these compounds are
      employed in all productive and household activities. The main cause of
      groundwater contamination is the infiltration of industrial wastewater: in the
      Province of Mantova, for example, organic chlorinated solvents have their origin
      in the NaOCl wastewater treatment for ammonia removal. Organic alogenated
      compounds in waters intended for human consumption in Lombardy are present in 510
      wells over 92 townships, affecting a population of 1,934,133 equivalent to 20% of
      the total resident population (1991 data). Maximum observed concentrations are
      related to trielin and tetrachloroethilene. Water treatment was achieved through
      aeration (stripping) and activated carbon or resin adsorption; in a few
      instances, also hydraulic interventions were implemented.

PMID- 8279718
TI  - Presence and importance of organochlorine solvents and other compounds in
      Germany's groundwater and drinking water.
AB  - Organochlorine compounds are widely used in Germany although the inland
      production of chlorinated solvents has greatly decreased since 1985. Data on
      groundwater contamination are incomplete, but there are some regional data sets
      from the States (Lander). Approximately 25% of the groundwater samples contain
      more than 1 microgram/l of a single solvent, the most prominent ones being tri-
      and tetrachloroethene, 1,1,1-trichloroethane and dichloromethane, but also
      chloroform. The most important causes for contaminations of the groundwater are
      unprotected storage and leaking sewage systems. Abandoned waste sites are,
      besides chlorinated compounds, also a source of many other contaminants. A
      ranking procedure according to their exposure potential (concentration,
      incidence, toxicology) is proposed. The compound of greatest concern is vinyl
      chloride, which is formed from tri- and tetrachloroethene under reducing
      conditions in the subsoil. The most important contaminant in drinking water is
      tetrachloroethene followed by 1,1,1-trichloroethane and trichloroethane.
      Chlorobenzene may also be present on occasion, while only about 20% of the
      finished drinking waters contain more chloroform after treatment than before.
      Only about 10% of all analyses of drinking water derived from groundwater shows
      the presence of organochlorine solvents and most of these show total
      concentrations less than 2 micrograms/l. The degradation product, vinyl chloride,
      was found up to now only in different groundwaters. To stabilize and to improve
      the situation, which still is much more favorable for drinking than for
      groundwater, precautions are going to be taken which should assure that these and
      other problematic substances which endanger water are used only in closed systems
      and rigid safety measures be imposed on their disposal and transport.

PMID- 8279719
TI  - Advances in research on carcinogenic and genotoxic by-products of chlorine
      disinfection: chlorinated hydroxyfuranones and chlorinated acetic acids.
AB  - The introduction of chlorination of public drinking water in the early 1900's was
      a major factor in the fight against waterborne disease. In the 1970's it was
      discovered that chlorine reacted with naturally occurring organic constituents,
      particularly in surface water, to yield small quantities of chlorinated by
      products such as chloroform for which regulations were subsequently developed.
      Since then there has been shown to be a substantial number of other by-products
      some in concentrations of a few nanograms/l and others similar concentrations to
      the THM. Of particular note are the potent bacterial mutagen MX and the
      chlorinated acetic acids. Current research into the significance of these for man
      is described and the key issues for risk assessment are identified.

PMID- 8279720
TI  - The impact of inorganic chemicals on water quality and health.
AB  - Inorganic substances constitute by far the greatest proportion of chemical
      contaminants in drinking water. They are present in greatest quantity as a
      consequence of natural processes but several important contaminants are present
      as a result of man's activities. Some of the most important even come from the
      plumbing material through which water is passed. Inorganic contaminants are the
      most important determinands of acceptability to the consumer, affecting taste,
      colour and scale deposition on pipes and fittings. They are also demonstrably the
      most important for health, having both beneficial and adverse effects which have
      been shown in human populations. This is a brief review of some of the most
      important inorganic constituents of drinking water covering major elements such
      as hardness and nitrate and more minor constituents in terms of quantity, such as
      arsenic, selenium and lead.

PMID- 8279721
TI  - Some aspects related to the presence of aluminium in waters.
AB  - Aluminium is present in very small amounts in living organisms but it is abundant
      in the environment, where it exists in forms with low availability to man and
      most biological species. Despite its abundance in the earth's crust only a small
      amount of aluminium is present in waters, with concentrations varying from a few
      tens to some hundreds of micrograms per liter. High levels of aluminium in
      drinking water are in most cases due either to acid precipitation or water
      treatment with aluminium salts. The presence of aluminium in dialysis fluids has
      been recognized as the major reason for development of aluminium toxicity in
      patients with renal failure. In subjects with normal renal function, high
      concentrations of this element in drinking water (> 80 micrograms/l) have been
      related to an elevated incidence of Alzheimer's disease, even though the real
      contribution of the element in the development of the disease has not yet been
      clarified.

PMID- 8279722
TI  - Assessment of the human risk associated with the presence of carcinogenic
      compounds in drinking water.
AB  - Both organic and inorganic contaminants which have been implicated in causing
      cancer in man or, more commonly, in laboratory animals can be found in drinking
      water. Apart from arsenic there are none for which there is convincing
      epidemiological evidence of a significant risk to man. However environmental
      epidemiology is fraught with difficulties. There are also difficulties in
      interpreting laboratory animal data and extrapolating this to the low
      concentrations found in drinking water although mathematical models can be very
      useful if used sensibly. There is a danger that the rather extreme public
      perception of cancer could lead to over regulation of some contaminants in water,
      possibly with an increase in risk from other hazards such as microbiological
      contamination.

PMID- 8279723
TI  - Reproductive risks from contaminants in drinking water.
AB  - Reproductive toxicity is a complex subject which, besides birth defects or
      sterility, includes adverse effects which may be less readily observed but more
      relevant to chronic low-level exposures (e.g., impaired functional development of
      target organs or systems, secretion of toxic chemicals in maternal milk). Sodium
      chlorite, when present at high concentration, may be related to impaired
      reproduction; among water chlorination by-products, further research is required
      on the developmental toxicity of chloroacetic acid and dichloro- and trichloro
      acetonitrile. Among the water pollutants which may pose significant developmental
      hazards, risk assessments have been performed for nitrates/nitrites, fluorides
      and lead. Molinate (a herbicide), dibromochloropropane (a nematocide) and the
      halogenated contaminants ethylene dibromide and epichlorohydrin show an almost
      selective male reproductive toxicity, although they are likely to pose a risk
      mainly at occupational exposure conditions. Ethylene thiourea, an environmental
      metabolite of some fungicides is markedly teratogenic in the rat: however, other
      toxic effects are induced at levels of exposure significantly lower than the
      teratogenic ones. Such poorly water-soluble compounds as TCDD or
      hexachlorobenzene also need to be considered, because of their remarkable
      potentials for reproductive toxicity. Finally, it should be noted that the data
      on reproductive toxicity for a number of chemicals do not allow a risk assessment
      at present: this holds true also for some substances which might pose concerns on
      the basis of their levels in drinking water (e.g. tetrachloroethylene, nickel).
      Another area which deserves more attention is the investigation of the possible
      interactions of several contaminants present together at low levels.

PMID- 8279724
TI  - Sanitary implications associated with the use of eutrophic freshwater.
AB  - This review presents the problem of eutrophication of lakes whose waters are used
      also for potable use. The indirect negative impact of algal blooms as well as the
      direct consequences of the overgrowth of toxic Cyanophyta are considered.
      Problems for water treatment plants processing eutrophic raw water are exposed.
      Basic treatment will not easily remove algae or their by-products and increased
      use of chlorine will give rise to high levels of chlorinated by-products such as
      THM. Possible alternatives and improvements are suggested for the treatment of
      poor quality raw water to obtain high quality drinking water.

PMID- 8279725
TI  - Revision of the WHO guidelines for drinking water quality.
AB  - This paper describes the activity of the World Health Organization in the field
      of drinking water quality, particularly the revision of the Guidelines for
      drinking water quality published in 1984. This process will be completed with the
      publication of new guidelines in 1993. The paper reports the physical, chemical
      and biological agents considered in the revision process, the procedure used to
      define the new guidelines, their meaning and their relationships with statutory
      limits.

PMID- 8279726
TI  - The role of the European Community in regulating water quality.
AB  - This paper summarizes the Community directives on water quality. In particular
      the directive on water for human consumption is discussed in relation to its
      philosophy, the procedure that was adopted for its preparation and the position
      of the Commission in respect to the more observations derived from the
      difficulties encountered by member states in its application. The role and the
      activity of the Institutions of the European Community as well as their
      relationships with member states are also discussed.

PMID- 8279727
TI  - Drinking water health advisory program.
AB  - The US Environmental Protection Agency prepares Health Advisories (HA) for
      drinking water contaminants. The HA provide technical guidance to public health
      officials or other interested groups on many aspects concerning drinking water
      contamination. The HA contain information on the chemistry, health effects,
      analytical methods and treatment technologies for specific contaminants. In
      addition, the HA include a risk assessment section which provides concentrations
      of the contaminant in drinking water that are not anticipated to cause adverse,
      noncancer health effects for 1 or 10 days or for longer exposures. Because the HA
      include risk assessments for less than lifetime exposures, they are useful when
      accidental spills occur or when regulatory limits are temporarily exceeded. The
      guidance documents are updated when new information becomes available that would
      change the previous conclusions.

PMID- 8279728
TI  - [Toward a renewal of knowledge in psychiatry].
AB  - Practice in an open hospital and liberal milieu, collocated with contemporary
      scientific findings, has admitted the elaboration, during thirty years, of a new
      form of psychiatry. This "systemal psychiatry" has been described in thirteen
      works successively integrated and in many French and foreign publications. Its
      principle characteristics are; basis, formation and emergence, production, ways
      of research and meaning. Since it is directly derived from the experience of the
      patient, its interdisciplinary origin and its permanent openness contribute to
      the integration of man with his physico-biopsycho-sociocultural universe, and of
      its methods of analogy with a more open rationality. Because of this the systemal
      psychiatry is productive, particularly in research.

PMID- 8279729
TI  - [Developmental delay, anxiety, deprivation and neglect: psychodynamics of a case
      of new problems].
AB  - This paper presents the case of a young child who displays an important
      developmental delay as well as anxiety symptoms. His condition is seen as
      concomitant to his impoverished environment. An analysis of his living
      circumstances permits one to make the reasonable hypothesis that the causal
      factor for the child's condition is the pathological interpersonal relations that
      exist between the child and his parents rather than the objective factors of his
      environment. Bibliographical material from various sources is used to reinforce
      the hypothesis. As a consequence of this analysis and hypothesis, concepts such
      as maltreatment, neglect, abuse, and deprivation are seen as having advanced
      knowledge when they appeared, but as impeding research at the present time.

PMID- 8279730
TI  - [Uxoricide of Louis Althusser according to his autobiographical sketch. Comments
      on criminal psychiatry].

PMID- 8279731
TI  - [Autobiographies of Louis Althusser. Structure and contents: lucid or not?].

PMID- 8279732
TI  - [The self-regulation process, adjustment and defense. Interdisciplinary study].
AB  - The study of the processes of self-regulation and defense may serve as an example
      illustrating the interdisciplinary research in psychiatry. Belying on the
      topography of mental disturbance as described by the systemal method, this study
      can profit from the findings of animal ethology and oceanographyt++ and thus
      conceive of the diversity and integration of the defense mechanisms of living
      systems beloging to different levels in the hierarchy of species. These insights
      may contribute to a refinement of the analysis of the human defense mechanisms
      met in psychiatry. As an example of this an analysis of phobic avoidance is
      related.

PMID- 8279734
TI  - [Camille Claudel. Her psychiatric case history].
AB  - Camille Claudel was confined to a mental hospital in 1913, when she was 50. In
      fact she had been ill long before and it is that morbid personality which the
      author describes. Her life had always been a tragedy and her love for Rodin had
      nothing to do whatsoever with her illness; such a feeling was just a symptom of
      her diseases. She remained 30 years in hospital and she was considered as a
      paranoiac systematized chronic delirious patient. The author explains why such a
      case could not be judged differently in France in 1913. Whereas today it would be
      referred to as schizophrenic paranoid psychosis, with polymorphic delirious ideas
      and main persecution theme.

PMID- 8279733
TI  - [Neuro-psychiatric effects of cimetidine: a case report].

PMID- 8279735
TI  - [Psychological effects of heart surgery. Preliminary study].

PMID- 8279736
TI  - [Apropos of moral treatment in psychiatry].

PMID- 8279737
TI  - [The spectrum of bipolar disorders: a specific form of recurrent mania].

PMID- 8279738
TI  - [Recurrent depression without lithium therapy. A lost chance].
AB  - By four patients hospitalized for a depressive recurrent the favorable element of
      clinic evolution was a lithotherapy then bring the effect very rapidly (three to
      seven days) grace using gluconate of lithium. The lithium being antidepressant,
      the absence of lithotherapy tentative in the course of major depressive status
      recurrent is a loss of chance for patients.

PMID- 8279740
TI  - [Apropos of the Schreber case and current aspects].

PMID- 8279739
TI  - [Apropos of a misdiagnosed form of paranoia: paranoia of the elderly].
AB  - The expression of elements of a paranoid symptomatology (suspicion, mistrust,
      hostility, etc.) is frequently seen in the elderly patients. Paranoid symptom is
      non-specific in geronto-psychiatric practice. The association with a cognitive
      disorder is frequent. The relationship between this trouble and a previous
      paranoid personality disorder appears, according to literature, looser than in
      the younger patients. The paranoid behavioral pattern often stands for the
      elderly as a defense against feelings of inferiority and humiliation. The
      expression of a paranoid symptomatology is a hamper for the subject's social
      autonomy, as well as an actual risk factor so far as it may involve a delay in
      the demands for medical care. Therapeutical attitudes, reassurant and preventing
      the patient from a rough awareness of his deficit, seem to be useful in the
      alleviation of the trouble.

PMID- 8279741
TI  - [Different theories of memory: which to choose?].

PMID- 8279742
TI  - [An original institution for interdisciplinary research].
AB  - The growing volume of available scientific information gives an incitement to
      extract general features, which may open new horizons for certain disciplines. A
      Center for reflections of this kind has been created in Roskilde (Denmark). Its
      originality consists in uniting "without walls" research workers with various
      backgrounds and in having branches in different countries. Its realization,
      advantages, inconveniences and projects are related and discussed.

PMID- 8279743
TI  - [Body function, therapy and individual psychology compared].

PMID- 8279744
TI  - [Use of role-playing in child psychotherapy and psycho-pedagogy].
AB  - Spontaneous role-playing in children stands as a contribution in generating and
      in improving social behaviors. Spontaneous role-playing is a part of the child's
      maturing process. Its characteristics: it does not follow any logical pattern; it
      is frequently repeated; its emotional involvement is important, without
      ambivalence. Educational role-playing attempts to help the child in coping with a
      peculiar interpersonal situation. Therapeutical role-playing may be used in
      helping children suffering from a definite impairment of social skills--or from
      any psychological or medical problem. We report an example of the use of
      therapeutical role-playing in a group of diabetic children suffering from
      disorders in interpersonal relationships arisen at the time of the onset of their
      physical illness.

PMID- 8279745
TI  - [Evaluation of affective dependence: validation study of the Hirschfeld et al.
      Inventory of Interpersonal Dependence].

PMID- 8279746
TI  - Critical steps in breast carcinogenesis.

PMID- 8279747
TI  - Growth suppression of normal mammary epithelial cells by wild-type p53.
AB  - We examined the status of the p53 gene in the HC11 normal mammary epithelial
      cells. Two mutations were identified: a Cys to Trp change at codon 138 and a
      microdeletion of codon 123 to 130 resulting from mutation of the splice acceptor
      site. These two mutations were independent, and no wild-type p53 allele was
      found. Introduction of wt-p53 strongly inhibited growth in monolayer. Thus, the
      absence of wt-p53 can be sufficient for the immortalization of mammary cells.

PMID- 8279748
TI  - A locus on chromosome 17p13.3, associated with a high S-phase index is distinct
      from the p53 gene in breast cancer.

PMID- 8279749
TI  - Production of cytokines and response to them in normal and transformed human
      mammary epithelial cells.

PMID- 8279750
TI  - Expression of colony-stimulating factor-1 and its receptor (the protein product
      of c-fms) in invasive breast tumor cells. Induction of urokinase production via
      this pathway?

PMID- 8279751
TI  - NM23.H1 loss of heterozygosity in human mammary carcinomas. Definition of a
      deletion map on chromosome 17q.

PMID- 8279752
TI  - Marker expression and differentiation in human breast cancer.

PMID- 8279753
TI  - Evidence of epithelial expression of progesterone receptor in breast cancers with
      marked fibrosis and limited metastatic node diffusion.

PMID- 8279754
TI  - Breast thermography is a noninvasive prognostic procedure that predicts tumor
      growth rate in breast cancer patients.
AB  - Our recent retrospective analysis of the clinical records of patients who had
      breast thermography demonstrated that an abnormal thermogram was associated with
      an increased risk of breast cancer and a poorer prognosis for the breast cancer
      patient. This study included 100 normal patients, 100 living cancer patients, and
      126 deceased cancer patients. Abnormal thermograms included asymmetric focal hot
      spots, areolar and periareolar heat, diffuse global heat, vessel discrepancy, or
      thermographic edge sign. Incidence and prognosis were directly related to
      thermographic results: only 28% of the noncancer patients had an abnormal
      thermogram, compared to 65% of living cancer patients and 88% of deceased cancer
      patients. Further studies were undertaken to determine if thermography is an
      independent prognostic indicator. Comparison to the components of the TNM
      classification system showed that only clinical size was significantly larger (p
      = 0.006) in patients with abnormal thermograms. Age, menopausal status, and
      location of tumor (left or right breast) were not related to thermographic
      results. Progesterone and estrogen receptor status was determined by both the
      cytosol-DCC and immunocytochemical methods, and neither receptor status showed
      any clear relationship to the thermographic results. Prognostic indicators that
      are known to be related to tumor growth rate were then compared to thermographic
      results. The concentration of ferritin in the tumor was significantly higher (p =
      0.021) in tumors from patients with abnormal thermograms (1512 +/- 2027, n = 50)
      compared to tumors from patients with normal thermograms (762 +/- 620, n = 21).
      Both the proportion of cells in DNA synthesis (S-phase) and proliferating (S
      phase plus G2M-phase, proliferative index) were significantly higher in patients
      with abnormal thermograms. The expression of the proliferation-associated tumor
      antigen Ki-67 was also associated with an abnormal thermogram. The strong
      relationships of thermographic results with these three growth rate-related
      prognostic indicators suggest that breast cancer patients with abnormal
      thermograms have faster-growing tumors that are more likely to have metastasized
      and to recur with a shorter disease-free interval.

PMID- 8279755
TI  - Breast carcinoma and the role of iron metabolism. A cytochemical, tissue culture,
      and ultrastructural study.
AB  - Transferrin receptors on proliferating and malignant cells are well documented.
      Iron is an essential micronutrient for cell growth that plays an important role
      in energy metabolism and DNA synthesis. Malignant cells requiring more iron
      modulate a transferrin receptor. Iron-bound transferrin interacts with this
      receptor, facilitating the transport of iron across the cell membrane.
      Transferrin is a glycoprotein and is the chief iron transport protein in
      mammalian blood. The more aggressive the tumor, the higher the transferrin
      receptor levels and the greater the proliferative index. We have found by
      cytochemical and ultrastructural studies that ferritin, an iron storage protein,
      is increased in breast cancer tissue. Anaplastic tumors have higher tissue
      ferritin levels. Tissue ferritin concentration may be an indirect method of
      measuring transferrin receptors and thus might be an index of proliferation and a
      prognostic indicator. Transferrin may be used as a carrier to target toxic
      therapy selectively to tumor tissue. A platinum transferrin complex (MPTC-63) has
      been developed and shown to be cytostatic in tissue culture, animal, and human
      studies. It also sensitizes tissue to agents that produce free radicals, such as
      adriamycin, and thus is synergistic with other drugs and radiation. Other
      transferrin complexes and conjugates of gallium, indium, and daunorubicin have
      also shown growth inhibition in tissue culture and animals. Human studies are in
      progress. By studying iron metabolism in breast cancer, we may be able to
      selectively inhibit tumor growth without toxic effects, and with other tumor
      biologic data be better able to select the stage I patient for adjuvant therapy.

PMID- 8279756
TI  - Clinical relevance of cell kinetics in breast cancer.

PMID- 8279757
TI  - Prognostic value of the S-phase fraction of breast cancers treated by primary
      radiotherapy or neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy for large operable breast cancers is being increasingly
      used for the purpose of "downstaging," so that the lesions become accessible to
      conservative treatment. Since tumor proliferative activity has been shown to be a
      major prognostic factor for breast cancers, we have studied the value of S-phase
      fractions established by flow cytometry on cytological samples at diagnosis, in
      184 stage II or IIIa patients entered in a randomized trial comparing neoadjuvant
      to adjuvant chemotherapy. All patients were pre- or perimenopausal, and the
      median follow-up was for 43 months (24-64). Using the median value (5%) as
      cutoff, a high SPF was found to be associated with relapse (p < 0.0008),
      locoregional recurrence (p < 0.02), or metastasis (p < 0.003). However, when the
      patients were analyzed according to the type of treatment, significance was
      maintained for the patients in the primary radiotherapy arm (p < 0.003) but not
      for those in the neoadjuvant chemotherapy arm (p < 0.06). The overall rate of
      response to neoadjuvant chemotherapy was significantly lower for tumors with low
      SPF (56.5%), compared to tumors with high SPF (85.6%). Thus, SPF was no longer
      predictive of outcome when the tumors regressed by more than 50% after
      chemotherapy (p = 0.66), whereas it was highly predictive in the nonresponding
      patients (p < 0.0001). Our study has revealed that patients with low-SPF tumors,
      irrespective of response or treatment schedule, had similar prognosis (around 70%
      free of disease at 45 months), while the high-SPF nonresponders had a dismal
      prognosis, with less than 25% free of disease at 24 months. If our results are
      confirmed with a longer follow-up, proliferative activity of breast cancers
      should prove to be instrumental for the initial therapeutic decision of stage II
      or IIIa patients.

PMID- 8279758
TI  - Tumor targeting potential and metabolism of 5-[125I]iodo-2'-deoxyuridine injected
      intratumorally in patients with breast cancer.
AB  - We have previously demonstrated the high tumor targeting potential of the
      thymidine analogue 125IUdR in experimental animal models following direct
      intratumoral or locoregional (intracavitary) administration. The aim of the
      present work was to evaluate the metabolism and selectivity (based on
      differential cell proliferation kinetics) of 125IUdR incorporation in patients
      with breast cancer following a similar approach. 125IUdR (4-8 MBq) was injected
      intratumorally by ultrasound-guided percutaneous injection in 7 patients with
      breast cancer 24 hours before ablative surgery. Blood and urine samples were
      collected up to 72 hours after injection and analyzed by HPLC using a C18
      reversed-phase column and methanol:water (20:80) as the mobile phase. Following
      resection, the radioactivity of the tumor and the surrounding tissues was
      measured in a gamma counter, and microautoradiography was performed on semithin
      tissue sections to determine the site of tracer incorporation at the cellular
      level. Activity in plasma peaked at 0.5 to 1 hour after 125IUdR injection (4.96
      +/- 1.08% of injected dose/liter), declining thereafter with a mean T1/2 of 11.24
      +/- 2.78 hours. By HPLC analysis, undegraded 125IUdR was about 15-30% of total
      plasma activity, with a biphasic pattern peaking at both 1-3 hours and
      approximately 12 hours. In addition to free 125I-, about 10% of early plasma
      activity was constituted by a labeled metabolite (tentatively identified as radio
      iodouracil), rising to about 50-60% at later time points. About 70-90% of urinary
      radioactivity was 125I-, and 5-20% was undegraded 125IUdR in the first 24-hour
      samples, while the remainder was iodouracil. High tumor/nontumor ratios were
      obtained (mean 147.4 +/- 125.2, range 27-397) with average tumor/blood ratios at
      the time of surgery equal to 32.7 +/- 18.6 (range 5-56). An average 0.0244 +/-
      0.0189% of the injected dose was present per gram of tumor (range 0.001-0.061%
      ID/g). Microautoradiography confirmed the high values of tumor/nontumor
      incorporation ratios and demonstrated the specificity of 125IUdR incorporation
      mostly in the tumor cell nuclei, with only occasional incorporation by normal
      appearing tubular cells. These results suggest the potential of radiolabeled IUdR
      for tumor targeting in humans, to be used whenever a satisfactory route of
      locoregional administration allowing for homogeneous tracer distribution within
      the tumor mass is accessible and in the presence of favorable tumor cell
      proliferations kinetics.

PMID- 8279759
TI  - Frequent mutations in breast cancer.

PMID- 8279760
TI  - Conservative surgery in breast cancer.

PMID- 8279761
TI  - The impact of reconstructive surgery in breast cancer.

PMID- 8279762
TI  - Reconstructive surgery in operable breast cancer. Critical evaluation.
AB  - In a large number of patients suffering from breast carcinoma the surgeon is
      still forced, for strictly technical reasons and/or by the patient's choice, to
      perform a radical operation that psychologically and practically compromises the
      quality of life of the patient, in varying degrees from patient to patient. The
      authors have analyzed the main characteristics of BR from the esthetic
      functional, psychological, and oncological points of view, in the light of a
      careful examination of the literature and of the data relating to a sample group
      of 500 BR treated according to a protocol in which BR has been included, with
      times and modalities depending on the histological type of tumor and the level of
      local evolution of the disease. The variety of BR techniques available is such as
      to permit this option in a great variety of cases. Whenever possible, immediate
      BR, with placement of a breast prosthesis at the same time or after positioning a
      tissue expander, is to be preferred. If additional skin or muscle is needed, BR
      is to be performed at a later time by means of more complex techniques
      (latissimus dorsi myocutaneous flap plus prosthesis, TRAM flap, free flap). When
      performed after adequate evaluation and in a technically valid way, BR gives good
      esthetic and psychological results, has a low incidence of complications or
      sequelae, and does not affect the natural history of the disease; in particular,
      BR does not change the percentage of local recurrence or its early diagnosis and
      allows adequate multidisciplinary treatment.

PMID- 8279763
TI  - Alternatives in immediate and delayed breast reconstruction. An overview.

PMID- 8279764
TI  - Radical mastectomy and immediate reconstruction with prosthesis. Experience with
      250 cases.

PMID- 8279765
TI  - Long-term results of conservation treatment of operable breast cancer.

PMID- 8279766
TI  - Treatment of locally advanced breast cancer without mastectomy. 5- and 10-year
      results of 135 tumors larger than 5 centimeters treated by external beam therapy,
      brachytherapy, and neoadjuvant chemotherapy.

PMID- 8279767
TI  - Biological markers for designing clinical protocols.

PMID- 8279768
TI  - Dose intensity. The neglected variable in clinical trials.

PMID- 8279769
TI  - The role of tumor-associated antigens in the biology and immunotherapy of breast
      cancer.

PMID- 8279770
TI  - Endocrine aspects of adjuvant treatment of breast cancer.

PMID- 8279771
TI  - Endocrine therapy of breast cancer. The experience of the Italian Cooperative
      Group for Chemohormonal Therapy of Early Breast Cancer (GROCTA).

PMID- 8279772
TI  - Endocrine factors in the outcome of systemic adjuvant therapy of early breast
      cancer.

PMID- 8279773
TI  - The EBCTCG overview of adjuvant therapy of breast cancer. What are the
      implications for future studies? Early Breast Cancer Trialists' Collaborative
      Group.

PMID- 8279774
TI  - The role of lonidamine in the treatment of breast cancer patients.

PMID- 8279775
TI  - A randomized trial on tamoxifen continuation during second-line hormone therapy
      in breast cancer.

PMID- 8279776
TI  - Somatuline and tamoxifen in postmenopausal breast cancer patients.

PMID- 8279777
TI  - A new schedule for clodronate treatment in patients with breast cancer and bone
      metastases.

PMID- 8279778
TI  - Quality of life--before, during, and after treatment.

PMID- 8279779
TI  - High dose intensity chemotherapy without bone marrow support: role of granulocyte
      macrophage colony-stimulating factor.

PMID- 8279780
TI  - Cancer therapy using radioimmunoconjugates. Implications for breast cancer.

PMID- 8279781
TI  - Stimulation of human breast cancer in vivo. Experimental findings and clinical
      results.

PMID- 8279782
TI  - Positron emission tomography of glucose metabolism in breast cancer. Potential
      for tumor detection, staging, and evaluation of chemotherapy.

PMID- 8279783
TI  - mAb-labeled liposomes in breast cancer cell targeting. Therapeutics and
      diagnostic use of polyspecific artificial carriers.

PMID- 8279784
TI  - Kinetic concepts in the treatment of breast cancer.

PMID- 8279785
TI  - Growth factors. Clinical implications in breast cancer.

PMID- 8279786
TI  - [Ethical limits of the current treatment of melanoma].

PMID- 8279787
TI  - [Combination of fotemustine-dacarbazine and interferon alpha in the treatment of
      metastatic malignant melanoma].
AB  - In the treatment of disseminated malignant melanoma (DMM), the results obtained
      with fotemustine associated or not with dacarbazine are promising and those
      obtained with interferon alpha are also interesting. Therefore, we have
      investigated the efficacy and the toxicity of a combined chemotherapy with
      fotemustine-dacarbazine and interferon alpha in DMM. We present in this work our
      results on 44 patients who entered into this opened study. 37 patients were
      evaluable. 29 (78.4 p. 100) had previously received one or more cytotoxic
      chemotherapy. The regimen consisted of an induction treatment with fotemustine
      (100 mg/m2) on days 1.8, and 60 dacarbazine (400 mg/m2) on days 1, and 60 and
      subcutaneous injections of interferon (9.10(6) UI) alpha three times weekly.
      Responding and stabilized patients were given maintenance treatment with a
      monthly infusion of fotemustine (100 mg/m2) and dacarbazine (400 mg/m2) and
      interferon alpha carried on at the same dose. The response rate was 10.8 p. 100
      (3 PR + 1 CR). Responses have depended on metastatic sites (cerebral site 18,2 p.
      100). The median duration of response was 28 weeks. Toxicity was mainly
      hematologic and was acceptable. These results are not as good as those reported
      before with fotemustine and dacarbazine. Even if reasons related to patients and
      protocol could be discussed, the association of interferon alpha, fotemustine and
      dacarbazine seems devoid of interest during induction treatment.

PMID- 8279788
TI  - [Streptococcus beta hemolytic necrotizing fasciitis. 5 cases in the Brussels
      area].
AB  - In the Brussels area five cases of necrotizing fasciitis occurred during the past
      two years in patients devoid of any pathology likely to lower the immune defence
      mechanisms. Alcoholism and the use of non-steroidal anti-inflammatory drugs seem
      to act as contributory factors. Necrotizing fasciitis develops alone or as
      complication of a pre-existent dermo-hypodermic infection. A massive use of
      antibiotics and a wide surgical slitting up failed to prevent a fatal issue in
      all five patients. Extremely early massive surgery remains vital in this disease.

PMID- 8279789
TI  - [Proteus syndrome].
AB  - We report the case of a 4-year old boy presenting with a polymalformative
      syndrome made of cutaneous and subcutaneous lesions associated with visceral and
      skeletal lesions. The cutaneous lesions consisted of 3 verrucous hamartomas, one
      haemangioma and one lymphangioma. The subcutaneous lesions were melting of
      panniculus adiposus, plantar tumefaction and diffuse lipomatosis of the
      peritoneal and retroperitoneal cavities. The skeletal lesions were uneven lower
      limbs and dorsal scoliosis. Atrophy of the intestinal villi was also found. The
      diagnosis of Proteus syndrome was made.

PMID- 8279790
TI  - [Patch-like sweat gland necrosis in AIDS].
AB  - Hard plaques located in pressure areas were observed in an HIV-infected male
      patient at the AIDS stage. Histological examination of the skin showed necrosis
      of the eccrine sweat glands. The relationship between this disease and eccrine
      neutrophilic hidradenitis observed in HIV infection is discussed. The authors
      propose a concept of eccrine sweat gland lesion spectrum.

PMID- 8279791
TI  - [Segmental neurofibromatosis].
AB  - Segmental neurofibromatosis is a rare form of the disease characterized by the
      unilateral location of cutaneous neurofibromas and cafe au lait spots along one
      or several dermatomes. It corresponds to the fifth type in Riccardi's
      classification. We report the 83rd case of segmental neurofibromatosis discovered
      by chance in an 83-year old woman presenting with isolated cutaneous
      neurofibromas situated on the right T10-L1 dermatomes. Type five
      neurofibromatosis is divided into four subgroups according to the uni- or
      bilateral site of the lesions, the presence or absence of a family history and
      the association, or lack of, with deep regional or systemic lesions. It is
      usually not hereditary, but due to a post-zygotic somatic mutation in the primary
      neural crest. The disease has a favourable prognosis: no case of evolution
      towards generalized neurofibromatosis has ever been reported.

PMID- 8279792
TI  - [Schnitzler syndrome and Waldenstrom disease. Fatal outcome of the original
      case].
AB  - The association between chronic urticaria, macroglobulinaemia and various other
      manifestations has been individualized as Schnitzler's syndrome. We report the
      terminal course of an original case followed up for 20 years, which ended as
      lymphoplasmocytic lymphoma with multiple sites, whereas no lymphomatous
      proliferation, meticulously looked for, had never been found hitherto. The
      lymphoma, associated with a macroglobulinaemia level above 5 milligrams, was
      diagnosed as Waldenstrom disease. Although most cases of Schnitzler's syndrome
      seem to follow a benign course (but the follow-up is not always long) a few cases
      have been reported showing evolution towards, or association with, lymphoma. This
      indicates that the follow-up of patients with Schnitzler's syndrome should be
      prolonged.

PMID- 8279793
TI  - [Disseminated cutaneous leishmaniasis in a case of an immunodepressed woman].
AB  - The authors report a case of Leishmania major leishmaniasis which occurred in a
      female kidney transplant recipient. In contrast with visceral leishmaniasis,
      disseminated cutaneous leishmaniasis seems to be exceptional in immunodepressed
      patients.

PMID- 8279794
TI  - [Acquired localized epidermolysis bullosa. A case with scalp involvement and
      immunoelectron microscopic study].
AB  - The case of a 59-year old man who had a clinical Brunsting-Perry pemphigoid
      localized to the scalp is described. Direct immunoelectron microscopy
      demonstrated IgG and C3 immune deposits in the anchoring fibril zone, as in
      epidermolysis bullosa acquisita. No circulating antibodies were detected by
      Western immunoblotting on epidermal and dermal extracts. These findings show that
      Brunsting-Perry pemphigoid is not an immunological entity and that it widens the
      clinical spectrum of epidermolysis bullosa acquisita.

PMID- 8279795
TI  - [Epidemiology and etiopathogeny of necrotizing fasciitis and streptococcal shock
      syndrome].
AB  - A significant increase in the frequency of necrotizing fasciitis caused by
      streptococci of group A has recently been noted. The disease usually appears in
      individuals without obvious risk factors. The initial lesion is often quite
      ordinary, and the evolution towards a toxic shock very swift. This evolution can
      be summarized as follows: 1) localized infection; 2) bacteraemia with circulating
      toxins and soft tissue necrosis; 3) production of cytokines by the immune cells
      of the host, leading to a rapidly irreversible toxic shock Serotypes 1, 3, 12 and
      28 of group A streptococcus are usually involved. The virulence of some serotypes
      might be explained by the acquisition of a toxic gene. The sensitivity of the
      host is linked to the genetic expression of the V. beta. elements on the surface
      of lymphocytes. Antibiotics cannot save the patient when necrotizing fasciitis is
      installed. Surgery must be massive and performed early.

PMID- 8279796
TI  - [A case for diagnosis: verrucous carcinoma of the foot].

PMID- 8279797
TI  - [Value and limits of fluidized bed in dermatology].

PMID- 8279798
TI  - [Value of Michel's medium in cutaneous histopathology].

PMID- 8279799
TI  - [Photoprotection in children].

PMID- 8279800
TI  - [Hair papilla, papillary fibroblast and their pathology].

PMID- 8279801
TI  - [Soaps and syndets].

PMID- 8279802
TI  - [Question of the month. Should treatment of Dubreuilh's melanoma be
      carcinologic?].

PMID- 8279803
TI  - [Psychotropic drugs in child and adolescent psychiatry].
AB  - Although there has been concern about the use of psychoactive drugs in children,
      evidence is accumulating that these drugs are beneficial. The various groups of
      currently available drugs are reviewed with their pharmacological
      characteristics, adverse effects, dosages, and uses in children. Benzodiazepines,
      both widely used and severely criticized, are effective when used correctly, in
      particular for the shortest possible length of time. Antidepressants are
      indicated in many conditions including depression, obsessive-compulsive
      disorders, and anxiety; some of their indications are specific to children, such
      as separation anxiety, enuresis, and school phobia. Neuroleptics have a less well
      defined role and are usually given as symptomatic treatment, although their use
      is limited by their side effects. This is also true of lithium, despite fairly
      good tolerability in children. Carbamazepine was introduced in psychiatry too
      recently to allow valid evaluation. Psychostimulants are viewed with fear in
      France despite their documented efficacy in hyperkinetic children. A few other
      drugs used in other fields of medicine are currently being investigated in
      psychiatry (beta-blockers, clonidine, naloxone). A debate on drugs used in child
      psychiatry is much needed in particular to overcome the methodological and
      ethical problems raised by controlled trials of which few have been conducted to
      date. Drug therapy should be combined with psychotherapy to place the target
      symptoms in perspective with regard to the child's overall make-up.

PMID- 8279804
TI  - [Autism and children with Fragile X syndrome].
AB  - Many epidemiological studies have demonstrated the exceptionally high incidence
      of autism in children with the fragile X syndrome, and autism is often considered
      a "behavioral phenotype" of this syndrome. However, the discrepancies between the
      results of these studies disclosed strong effects of methodological flaws and
      demonstrated the need for gathering clinical data. Atypical "autistic-like"
      behaviors were then found to be common, early symptoms of the syndrome occurring
      against the background of early manifestations of mental retardation. These
      behaviors reflect these children's exquisite reactivity to change and contact
      with others. Avoidance of eye contact is the most significant feature. The
      appropriate diagnosis is not autism but phobia of social relationships. This
      highly specific vulnerability, which may be inherited, probably leads some of
      these patients to experience the fate of autistic children. It highlights the
      influence of environment on the clinical course and indirectly supports the role
      of early specialized care.

PMID- 8279805
TI  - [Content analysis of parents' descriptions of their autistic, trisomy 21 or
      normal children].
AB  - As part of a study of the clinical evaluation of infantile autism, interviews of
      parents of autistic, Down's syndrome, or normal children were subjected to
      content analysis. Parental representations in the three groups were determined.
      Parents often (81%) described their autistic children as "nervous" and felt
      distressed by their perceived failure to understand their child (62%). These
      findings suggest working hypotheses in the fields of care and research.

PMID- 8279806
TI  - [Children and alcohol. A study in the school milieu].
AB  - Epidemiologic studies have consistently found that use of alcohol is increasing
      among teenagers and that children who have their first drink before the age of
      ten years are at increased risk for alcohol use during adolescence. In this
      study, a questionnaire was completed by 351 children (185 boys and 166 girls)
      aged 7 to 11 years in eight different schools in the Lille area (northern
      France). Most respondents (70.8%) reported previous experience with alcoholic
      beverages. Regular use of alcohol was reported by 8.7% of respondents and at
      least one episode of acute over-drinking by 23.6%. Attitudes towards alcohol and
      reasons for alcohol use varied across age groups. Use of alcohol produced guilt
      in the youngest children but was viewed as normal in the older age groups.
      Although some awareness of alcohol-related hazards was found, misconceptions were
      common. Use of alcohol was related to age and awareness: among the younger
      children, the level of awareness was significantly higher in regular users than
      in non-users, whereas the opposite was true in the older respondents. A positive
      correlation was found between current alcohol use and the children's predictions
      of future use. These data highlight the value of epidemiologic surveys for
      developing strategies aimed at preventing alcohol use in youngsters.

PMID- 8279807
TI  - [Psychiatric sequelae of diencephalic tumors in children. 3 case reports].
AB  - Three cases of behavioral disorders in children previously treated for a
      diencephalic tumor are reported. In such cases, classical psychiatric evaluation
      is difficult because reference data on childhood psycho-organic syndromes are
      lacking. Another complicating feature is that multiple factors contribute to the
      impairment of social interactions, including maladaptive reactions to disease
      related stress, sensory deficits, and cognitive disorders. A structured
      evaluation should be performed in order to assess the child's behavior, the
      psychological and educational environment, and impairment of neuropsychological
      and neurophysiological function.

PMID- 8279808
TI  - Anti-rhinoviral activity of recombinant and hybrid species of interferon alpha.
AB  - To define further differences in antiviral activity as well as to identify
      candidate interferons for study in the prevention of rhinovirus colds, the
      antiviral activities of nine species of recombinant interferon alpha (IFN-alpha
      A, IFN-alpha B, IFN-alpha C, IFN-alpha D, IFN-alpha J, [Ser-116]IFN-alpha J1, IFN
      alpha K, IFN-alpha J/C(Fnu4HI), and IFN-alpha A/D(BglII)) were evaluated against
      rhinovirus types 39 (RV 39) and 1A (RV 1A). WI-38 cells were exposed to various
      concentrations of each interferon and were then infected with RV 39, RV 1A, or
      VSV. Efficacy was determined by protection from cytopathic effect using a
      tetrazolium dye assay. The 50% inhibitory concentrations ranged from 4 +/- 3
      pg/ml for IFN-alpha C to > 3000 pg/ml for IFN-alpha D against RV 39, and from 6
      +/- 4 pg/ml for IFN-alpha J/C(Fnu4HI) to > 3000 pg/ml for IFN-alpha D against RV
      1A. IFN-alpha J/C(Fnu4HI), [Ser-116]IFN-alpha J1, and IFN-alpha C were the most
      active of the interferons, and were all more active than IFN-alpha A, against RV
      39, RV 1A, and VSV. These interferons warrant further study against rhinoviruses
      and other viruses.

PMID- 8279809
TI  - 5'-Hydrogenphosphonates of anti-HIV nucleoside analogues revisited: controversial
      mode of action.
AB  - The monomeric and symmetrical dimeric 5'-hydrogenphosphonate derivatives of AZT
      were prepared and evaluated for their inhibitory properties against HIV-1 in
      several cell lines. The synthesis of the compounds was achieved by reaction of
      AZT with in situ prepared phosphorus tris(imidazolide) or with phosphonic acid in
      the presence of pivaloyl chloride. The two title compounds showed in vitro anti
      HIV activity similar to (but not better than) that of AZT in three cell lines
      which were not deficient in thymidine kinase. On the other hand they were
      inactive in CEM-TK- cells. Pharmacokinetic studies in several media corroborate
      the assumption that these compounds must not be considered as 'true antiviral
      agents', but that they act by releasing their nucleoside entity.

PMID- 8279810
TI  - Intracellular delivery of nucleoside monophosphates through a reductase-mediated
      activation process.
AB  - On the basis of three different models (namely: ddU, AZT and PMEA),
      mononucleotide phosphotriester derivatives were designed to be able to liberate
      the corresponding monophosphate (or phosphonate) inside the cell through a
      reductase-mediated activation process. It was demonstrated that the use of bis[S
      (2-hydroxyethylsulfidyl)-2-thioethyl] esters of ddUMP (11), AZTMP (12) and PMEA
      (17) resulted in intracellular delivery of the parent monophosphate (or
      phosphonate). This point was corroborated by observation of an anti-HIV effect
      of, 11 in various cell lines, for 12 in CEM TK- cells and by the enhanced
      activity observed for 17. Furthermore, the reported decomposition data in cell
      extracts fully confirm the validity of this approach and show unambiguously the
      potential for intracellular reductase-mediated activation of the starting drug.

PMID- 8279811
TI  - Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus,
      and measles virus in vitro and their therapeutic efficacies for HSV-1 infection
      in mice.
AB  - One hundred forty-two kinds of traditional medicines, which have been
      historically used in China, Indonesia, and Japan, were examined for the antiviral
      activity of their hot water (HW) extracts against herpes simplex virus type 1
      (HSV-1), poliovirus type 1, and measles virus by plaque reduction assay. Thirty
      two, 55, and 30 HW-extracts of them showed anti-HSV-1, antipoliovirus, and anti
      measles virus activities, respectively. Among the 32 HW-extracts with anti-HSV-1
      activity, 3 HW-extracts had anti-HSV-1 activity alone and the others showed anti
      HSV-1 activity with anti-poliovirus and/or anti-measles virus activities. The 32
      HW-extracts were further examined for their therapeutic efficacies of HSV-1
      infection in mice. The mice were infected cutaneously with HSV-1 and HW-extracts
      were orally administered three times daily. Twelve HW-extracts, currently used
      for the treatment of various diseases other than viral infection, were found to
      be significantly effective in limiting the development of skin lesions and/or in
      prolonging the mean survival times of HSV-1-infected mice. These results
      suggested that 12 of 142 HW-extracts that exhibited therapeutic efficacy in an
      animal infection model were possible candidates for anti-HSV-1 traditional
      medicine.

PMID- 8279812
TI  - Inhibition of HIV infection by flavanoids.
AB  - Of a variety of flavanoids, the flavans were generally more effective than
      flavones and flavanones in selective inhibition of HIV-1, HIV-2 or SIV infection.
      Studies of their effects on the binding of sCD4 and antibody to gp120 indicated
      that the effective compounds interact irreversibly with gp120 to inactive virus
      infectivity and block infection.

PMID- 8279813
TI  - Constitutive interferon expression from retroviral vector.
AB  - A genomic fragment with the human beta-interferon gene was cloned into a pL3-4, a
      defective Moloney murine leukemia virus (M-MuLV) vector. Here we show that clones
      selected after viral infection of mouse NIH 3T3 cells constitutively produced 128
      IU/ml of human beta-interferon. Constitutive synthesis of retroviral RNA was
      confirmed by dot blot hybridization of RNA isolated from two of the selected
      clones. Poly(I) x poly(C) and cycloheximide induction resulted in an increased
      RNA level, but this was not reflected in an increased production of biologically
      active interferon.

PMID- 8279814
TI  - The role of tumor necrosis factor in viral disease.
AB  - Tumor Necrosis Factor (TNF) is one of the many cytokines that comprise a complex
      intertwined network of biological response modifiers that takes on extreme
      significance as the host response to infectious diseases. Soluble factors such as
      Interleukin-2 and Interferon-gamma released by T cells and Interleukin-1,
      Interleukin-6 and TNF released by monocytes have been shown to play key roles in
      proliferation, activation and differentiation of immune cells. It has also become
      evident that development of treatment modalities for infectious diseases is
      complicated by the complexity of this cytokine network. In the last decade
      numerous reports have presented data, often conflicting, which clearly
      demonstrate a role for TNF in the response to infections caused by viruses. This
      review summarizes this rapidly growing volume of data, discussing consistencies
      and discrepancies as appropriate. By better understanding the role of TNF in the
      host immune response, it may be possible to modulate this complex network for the
      benefit of the host in its battle against viral infection.

PMID- 8279815
TI  - Feline immunodeficiency virus infection of cats as a model to test the effect of
      certain in vitro selection pressures on the infectivity and virulence of
      resultant lentivirus variants.
AB  - Three groups of specific pathogen-free (SPF) domestic cats, each containing 5
      animals, were infected with one of three closely related FIV variants and
      monitored for 36 weeks. A fourth group of 5 cats was sham-infected and served as
      uninfected controls. FIV variants included: (1) a fully virulent animal passaged
      FIV-Petaluma; (2) a Crandell feline kidney (CrFK) cell-adapted FIV-Petaluma (FIV
      CrFK); and (3) a variant of FIV-CrFK (FIV-CrFKAZT) that had been selected in
      vitro for resistance to azidothymidine. Cats infected with fully virulent FIV
      Petaluma strongly seroconverted, became persistently viremic, and exhibited
      lymphadenopathy, neutropenia, and inversion of the CD4+:CD8+ T cell ratio. Cats
      infected with FIV-CrFK seroconverted but the antibody responses were much weaker
      and more variable; two of the cats became transiently viremic and no hematologic
      abnormalities or clinical signs of illness other than a very mild lymphadenopathy
      were observed. None of the five cats inoculated with FIV-CrFKAZT seroconverted,
      became viremic, or exhibited any gross or hematologic signs of disease, even
      though proviral DNA was transiently detected in tissue following inoculation.
      This study demonstrates that the FIV infection model can be used to assess
      differences in the virulence of FIV variants, including variants selected for
      antiretroviral drug resistance.

PMID- 8279816
TI  - Novel indolocarbazole protein kinase C inhibitors prevent reactivation of HIV-1
      in latently infected cells.
AB  - Suppression of human immunodeficiency virus-1 (HIV-1) reactivation in latently
      infected cells by protein kinase C (PKC) inhibitors has been described. Based on
      an initial finding with the indolocarbazole inhibitor Go 6976 we have examined
      several members of this new class of potent and specific PKC inhibitors with
      respect to their ability to prevent the PKC-mediated induction of HIV-1
      replication in the latently infected U1 cell line. Two of these compounds
      strongly inhibited not only PMA-induced release of p24-antigen and infectious
      virus particles into the supernatant (50% inhibition at 0.04-0.35 microM) but
      also TNF-alpha-mediated HIV-1 reactivation in the same concentration range.
      Significant lower toxicities compared to Go 6976 were observed for the new
      compounds, with 50% cytotoxic concentrations at 5.2 microM for Go 7775 and 3.4
      microM for Go 7716. This resulted in selectivity indices which were 10-20-times
      higher compared to the reference compound Go 6976 and were comparable to those of
      registered anti-AIDS drugs. No anti-HIV-1 activity was observed for a closely
      related indolocarbazole analogue with no inhibitory activity in the PKC in vitro
      enzyme assay. This study demonstrates the important role of PKC in reactivation
      of HIV-1 in latently infected cells and points to the potential of
      indolocarbazoles to preserve the latent state of HIV-1 infection.

PMID- 8279817
TI  - Reversal of the antiviral activity of ribavirin against Sindbis virus in Ae.
      albopictus mosquito cells.
AB  - Earlier work in our laboratory has shown that the replication of Sindbis virus in
      Aedes albopictus mosquito cells is inhibited by ribavirin (Rbv) and mycophenolic
      acid (MPA) (Sarver and Stollar (1978) Virology 91, 267-282; Malinoski and Stollar
      (1980) Virology 102, 473-476). We report here that the antiviral effect of Rbv
      and MPA can be reversed by depriving infected cells of methionine or isoleucine,
      or by treating them with fluorodeoxyuridine (FUdR) or cycloleucine. We suggest
      that, as was the case when the antiviral activity of Rbv was reversed by
      actinomycin D (Malinoski and Stollar (1981a) Virology 110, 281-291), these
      effects may be mediated by changes in the GTP pools of treated cells.

PMID- 8279818
TI  - Ribavirin efficacy in an in vivo model of Crimean-Congo hemorrhagic fever virus
      (CCHF) infection.
AB  - After intraperitoneal (i.p.) infection of infant mice with CCHF virus, virus
      titers in liver remained significantly higher than in other organs except blood
      (serum). Within the liver, virus antigen was first found by immunofluorescence
      (IFA) in Kupffer cells followed by more extensive hepatic spread. Later, virus
      was found in other organs including brain and heart. Ribavirin treatment
      significantly reduced infant mouse mortality and extended the geometric mean time
      to death. Ribavirin treatment reduced CCHF virus growth in liver and
      significantly decreased, but did not prevent, viremia. Despite a substantial
      viremia, infection of other organs including brain and heart was not detected in
      ribavirin-treated mice. A hepatotropic virus subpopulation with less
      neurovirulence than the parent was isolated from liver of ribavirin-treated mice
      (single dose, 100 mg/kg). After serial passage in placebo-treated mice, the
      exclusive hepatotropism was lost.

PMID- 8279819
TI  - Quercetin potentiates TNF-induced antiviral activity.
AB  - Tumor necrosis factor (TNF) produces a dose-dependent inhibition of vesicular
      stomatitis virus (VSV), encephalomyocarditis virus (EMCV), and herpes simplex
      virus type 1 (HSV-1) replication in WISH cells. The antiviral activity of TNF
      against VSV and EMCV is greatly enhanced by combination with quercetin. Induction
      of 2',5'-oligo-adenylate (2-5A) synthetase by TNF is also enhanced by quercetin.
      Addition of polyclonal antibodies to human interferon (IFN)-beta completely
      blocked both enhancement of antiviral activity and 2-5A synthetase induction.

PMID- 8279820
TI  - Microbial growth kinetics: a historical perspective.

PMID- 8279821
TI  - Nutrient-limited microbial growth kinetics: overview and recent advances.
AB  - Traditional concepts of nutrient uptake and growth kinetics as linked by cell
      yield are presented. Phenomena affecting the kinetics are examined along with a
      discussion of those which lead to ambiguity. Concepts of flux control are
      presented to help understand the distribution of material along metabolic
      pathways. Specific affinity is described to relate nutrient accumulation rates to
      transporter density. It is shown to be a primary kinetic constant and the best
      available index of nutrient collection ability. As an aid to understanding,
      specific affinity is reexpressed in terms of membrane permeability. Formulations
      of nutrient transport rate as a function of cellular composition, particularly
      transporter and enzyme content and known as janusian kinetics, are described as
      an improvement to specific affinity theory. Procedures for quantified
      unidirectional fluxes are reviewed to identify the difference between gross and
      net transport rates of substrate. Collision frequency theory is used to show that
      in addition to total biomass, cell size and transporter density should also be
      included in rate equations describing microbial growth. Theory diversity suggests
      that one reason for microbial metabolic is that the likelihood of additional
      collisions of substrate molecules with a cell surface, after an initial
      collision, requires only a sparse distribution of transporter sites for maximal
      rate, leaving room for additional transporters able to collect other substrate
      types.

PMID- 8279822
TI  - The relationship between cell and population growth.
AB  - A steady-state model of cell volume frequency distribution using the method of
      Williams (1971) is derived. Results are compared to a Monte Carlo simulation of
      cell growth and division. It is suggested that the Monte Carlo method might be of
      value for investigating cell and population properties for which analytic methods
      are not currently available.

PMID- 8279823
TI  - Concentrations and fluxes of organic carbon substrates in the aquatic
      environment.
AB  - Data concerning concentrations and fluxes of dissolved organic compounds (DOC)
      from marine and lacustrine environments are reviewed and discussed. Dissolved
      free amino acids and carbohydrates comprised the main fraction in the labile
      organic carbon pool. Dissolved free amino acids in marine waters varied between 3
      1400 nM and those of fresh waters between 2.6-4124 nM. Dissolved free
      carbohydrates varied between 0.4-5000 nM in marine systems and between 14-111 nM
      in fresh waters, The turnover times of both substrate pools varied in marine
      waters between 1.4 hours and 948 days and in fresh waters between 2 hours and 51
      days. Measurements of stable 12/13C-ratio and 14C-isotope dating in ocean deep
      water samples revealed DOC turnover times between 2000-6000 years. Studies on
      carbon flows within the aquatic food webs revealed that about 50% of
      photosynthetically fixed carbon was channelled via DOC to the bacterioplankton.
      Excreted organic carbon varied between 1-70% of photosynthetically fixed carbon
      in marine waters and between 1-99% in fresh waters. The labile organic carbon
      pool represented only 10-30% of the DOC. The majority (70-90%) of the DOC was
      recalcitrant to microbial assimilation. Only 10-20% of the DOC could be easily
      chemically identified. Most of the large bulk material represented dissolved
      humic matter and neither the chemical structure nor the ecological function of
      the DOC is as yet clearly understood.

PMID- 8279824
TI  - Carbohydrate transport in bacteria under environmental conditions, a black box?
AB  - A typical eubacterium carries a battery of substrate transport systems which are
      the ultimate pacemakers for growth. These systems reflect a billion year old
      selection for coping with rapidly changing conditions in the environment and each
      of them is optimised for specific growth conditions. Metabolic pathways in
      combination with transport systems can be interpreted as transient sensory
      systems, where a transport system corresponds to a sensor for external stimuli.
      Characteristics is a tightly linked common control between a carbohydrate
      metabolic pathway and the corresponding transport system. Many of the observed
      growth phenomena are a direct result of adaptation and regulation of transport
      capacity to rapid changes in environmental conditions. Some of the better
      understood examples are discusses. Nevertheless, knowledge on bacterial
      carbohydrate transport under environmental conditions as documented in the
      literature is still scarce.

PMID- 8279825
TI  - Kinetics of microbial growth with mixtures of carbon sources.
AB  - Several investigations have shown that during growth in carbon-limited chemostats
      the simultaneous utilisation of carbon substrates which usually provoke diauxie
      under batch conditions, i.e., 'mixed substrate growth,' is probably the rule
      under ecologically relevant growth conditions. In contrast, the models presently
      available for the description of the kinetics of microbial growth are all based
      on the use of single substrates. Systematic studies in chemostat culture have
      shown that steady-state residual concentrations of individual compounds were
      consistently lower during mixed substrate growth than during growth with the
      single substrates. This effect is clearly demonstrated for the case of
      Escherichia coli growing with mixtures of glucose plus galactose. The data
      presented indicate that the extent of reduction of steady-state residual
      substrate concentration is dependent on the proportions of the substrates in the
      mixture, the nature of substrates mixed and the regulation pattern of enzymes
      involved in their breakdown. If this behaviour can be shown to be typical for
      growth under environmental conditions, it may provide an explanation why microbes
      still grow relatively fast at the low substrate concentrations encountered in
      nature.

PMID- 8279826
TI  - Growth kinetics and competition--some contemporary comments.
AB  - Results of competition experiments with one growth-limiting factor under
      idealized experimental conditions have been reported extensively, and usually
      provide ample support for the conclusion that 'complete competitors cannot
      coexist'. However, under conditions of multiple substrate limitation and
      discontinuous or alternating supply of nutrients, coexistence of species is quite
      common. Since such patterns of nutrient supply may be expected to prevail in many
      natural environments the mechanisms ruling the survival and growth of bacteria
      under such conditions need to be understood. However, it appears that
      surprisingly little is known of the physiological state of individual competing
      species grown in mixed cultures. Unfortunately, basic information such as the
      actual concentration of limiting nutrients is lacking in most cases. But perhaps
      the recent development of new and powerful techniques to explore the
      physiological properties even of individual cells will further stimulate studies
      into the mechanisms behind the competitiveness of microbial species.

PMID- 8279827
TI  - Control and regulation of metabolic fluxes in microbes by substrates and enzymes.
AB  - The control of enzymes and substrates on the flux through microbial metabolic
      pathways can be quantified in terms of flux control coefficients. In pathways
      involving group transfer, the summation theorem for flux control by the enzymes
      has to be modified: the sum of control by all enzymes is between 1 and 2. The
      phosphoenolpyruvate:glucose phosphotransferase system is such a pathway.
      Experimental determination of the control by the enzymes in this pathway is under
      way. The control of the enzymes on the glycolytic flux in yeast is low, with the
      possible exception of the uptake step. In Klebsiella pneumoniae potassium and
      ammonium ions can simultaneously be 'limiting', (i.e. have significant control on
      growth) at pH6, but not at pH8. This may be due to the fact that at pH8 the high
      affinity potassium uptake system is absent.

PMID- 8279828
TI  - How do non-differentiating bacteria adapt to starvation?
AB  - Non-differentiating bacteria adapt to starvation induced growth arrest by a
      complex turn-on/turn-off pattern of protein synthesis. This response shows
      distinct similarities with those of spore formation in differentiating organisms.
      A substantial amount of information on the non-growth biology of non
      differentiating bacteria can be derived from studies on Vibrio strains. One
      important result is that carbon rather than nitrogen or phosphorus starvation
      leads to the development of a starvation and stress resistant cell in these
      organisms. Hence, we have attempted to characterize the carbon starvation
      stimulon. By the use of two-dimensional gel electrophoresis of pulse-labelled
      cells and transposon mutagenesis, using reporter gene constructs, the identity
      and function of some members of the carbon starvation stimulon have been
      elucidated. Moreover, regulatory genes of the starvation response have been
      identified with these techniques. Current studies primarily address the identity
      and function of these genes. The role of transcript modification and stability
      for both long term persistence during starvation as well as the efficient
      recovery of cells which occurs upon nutrient addition is also addressed. It is
      suggested that an understanding of the functionality of the translational
      machinery is essential for the understanding of these adaptive pathways. This
      contribution also discusses the diversity of the differentiation-like response to
      starvation in different bacteria and whether a general starvation induced
      programme exists.

PMID- 8279829
TI  - Kinetics of growth and sugar consumption in yeasts.
AB  - An overview is presented of the steady- and transient state kinetics of growth
      and formation of metabolic byproducts in yeasts. Saccharomyces cerevisiae is
      strongly inclined to perform alcoholic fermentation. Even under fully aerobic
      conditions, ethanol is produced by this yeast when sugars are present in excess.
      This so-called 'Crabtree effect' probably results from a multiplicity of factors,
      including the mode of sugar transport and the regulation of enzyme activities
      involved in respiration and alcoholic fermentation. The Crabtree effect in S.
      cerevisiae is not caused by an intrinsic inability to adjust its respiratory
      activity to high glycolytic fluxes. Under certain cultivation conditions, for
      example during growth in the presence of weak organic acids, very high
      respiration rates can be achieved by this yeast. S. cerevisiae is an exceptional
      yeast since, in contrast to most other species that are able to perform alcoholic
      fermentation, it can grow under strictly anaerobic conditions. 'Non
      Saccharomyces' yeasts require a growth-limiting supply of oxygen (i.e. oxygen
      limited growth conditions) to trigger alcoholic fermentation. However, complete
      absence of oxygen results in cessation of growth and therefore, ultimately, of
      alcoholic fermentation. Since it is very difficult to reproducibly achieve the
      right oxygen dosage in large-scale fermentations, non-Saccharomyces yeasts are
      therefore not suitable for large-scale alcoholic fermentation of sugar-containing
      waste streams. In these yeasts, alcoholic fermentation is also dependent on the
      type of sugar. For example, the facultatively fermentative yeast Candida utilis
      does not ferment maltose, not even under oxygen-limited growth conditions,
      although this disaccharide supports rapid oxidative growth.

PMID- 8279830
TI  - Dynamics of microbial growth and metabolic activity and their control by
      aeration.
AB  - The optimization of fermentation processes depends to a large extent on the
      modelling of microbial activity under complex environmental conditions where
      aeration is an important limiting and control factor. Simple relationships are
      used to establish the sensitivity of cultures to oxygen stress. Specific
      limitation coefficients which can be determined in laboratory reactors allow a
      projection to industrial operation and the definition of appropriate aeration and
      agitation profiles. Optimum control can be assured on the basis of directly
      measurable process parameters. This is shown for the case of ethanol production
      using S. cerevisiae at high cell dry weight concentrations.

PMID- 8279831
TI  - Kinetics of microbial product formation and its consequences for the optimization
      of fermentation processes.
AB  - Different types of product formation kinetics are discussed with respect to their
      significance for fermentation process economics. Microbial products belonging to
      various classes are formed in a growth-coupled manner. It is often found that the
      specific rate of product formation increases with the specific growth rate,
      approaching a maximum at higher growth rates. It is illustrated that for such
      types of relationship between the product formation rate and the growth rate
      process conditions are optimal when the specific rate of product formation is
      about half-maximal.

PMID- 8279832
TI  - Healing moments.

PMID- 8279833
TI  - Roux en Y gastric bypass. Surgical treatment of morbid obesity.

PMID- 8279834
TI  - The new implant tracking regulations. Defining, implementing, documenting.

PMID- 8279835
TI  - AORN joins the American Society of Post Anesthesia Nurses for first collaborative
      educational effort. Sept 29 to Oct 2, 1993.

PMID- 8279836
TI  - Specialty surgical teams. Results of a study.
AB  - Perioperative nursing is changing in response to the increasing complexity of
      patient care during diverse, specialized surgical procedures. As a result,
      designated specialty surgical teams have evolved to fulfill needs of the patient,
      nurse, and surgeon. This exploratory, descriptive study examined reasons for
      implementing specialty surgical teams, the frequency and composition of such
      teams, and their perceived benefits. Data concerning the prevalence and specific
      use of specialty surgical teams are necessary to validate and redefine the nature
      and role of specialized perioperative nurses.

PMID- 8279837
TI  - Establishing a preadmission clinic. A model for quality service.

PMID- 8279838
TI  - ["State of the art" of chemotherapy for lung cancer].
AB  - This paper reviews the recent clinical trials of chemotherapy and combined
      modality therapy in small-cell lung cancer (SCLC) and non-small cell lung cancer
      (NSCLC). 1) A meta-analysis has shown that survival is prolonged when
      radiotherapy is used in combination with chemotherapy in the treatment of limited
      stage SCLC. A randomized trial comparing early radiotherapy (RT) with late RT has
      reported the survival advantage in the early RT. Recent pilot trials employing
      accelerated hyperfractionated RT with concurrent cisplatin (CDDP) and etoposide
      have shown encouraging survival results. 2) The approach to increasing dose
      intensity has been attempted in the treatment of extensive-stage (ES) SCLC. The
      most common approach is weekly chemotherapy. Results of pilot studies using this
      approach have shown the relatively high rate of complete response with an average
      of 36% and longer survival with a median of more than 10 months in ES-SCLC. 3)
      Combined modality treatment employing CDDP-containing chemotherapy or CDDP alone
      and radiotherapy have produced positive results in the treatment of locally
      advanced stage III A or III B NSCLC. In conclusion, despite the advances of
      treatment, the cure rate remains quite low in lung cancer. Further investigations
      are needed to improve the outcome with this disease.

PMID- 8279839
TI  - [State of the art of drug therapy in breast cancer].
AB  - Breast cancer should be recognised as a systemic disease even at the stage when
      metastatic dissemination is not clinically evident. Chemotherapy and endocrine
      therapy, as systemic treatments require appropriate assessment in the context of
      multi-disciplinary treatment of breast cancer. Postoperative adjuvant therapy is
      being standardised based upon several randomized trials. The concept of dose
      intensity was addressed through randomized trials. It was confirmed that dose
      intensity correlated with higher response rates, but the effect of dose-intensive
      treatments on survival still needs to be established. High-dose chemotherapy
      along with autologous bone marrow support is being evaluated for its safety and
      efficacy. This strategy is also applied for postoperative adjuvant therapy of
      high-risk patients. Several new chemotherapeutic agents have evaluated clinically
      during the last years. Taxol, taxotare, navelbine, and anthracycline MX2 have
      been found to have efficacy against breast cancer. Antiestrogen analogs, new
      aromatase inhibitors, and LHRH analogs have introduced into clinics recently and
      they are changing the outfit of endocrine therapy. Appropriate combination of
      chemotherapy and endocrine therapy induced improved quality of life of metastatic
      breast cancer patients.

PMID- 8279840
TI  - [Process of making a protocol for advanced gastric cancer chemotherapy--using 5'
      DFUR+CDDP as an example].
AB  - The process of making a protocol for advanced gastric cancer chemotherapy was
      reported by using an example of 5'-DFUR+CDDP. Patient selection and eligibility
      criteria, treatment method (Regimen A, 5'-DFUR 1,400 mg/m2/day, p.o. day 1-day
      4/w, and CDDP 80 mg/m2 i.v. day 5 q 3w, Regimen B, 5'-DFUR 1,400 mg/m2/day p.o.
      day 1-day 4/2w and CDDP 80 mg/m2 i.v. day 5 q 4w), Response criteria (by the
      Japanese Research Society for Gastric Cancer: The general rules for the Gastric
      Cancer Study, published in June, 1993. 12th edition), registration method
      (prestratification by cancer spread in patient's body: abdominal localized type,
      liver metastatic and/or ascitic type, distant type), proposal of potential
      response rate, method of analysis of results (effective rate (ER), median
      survival rate (MST), one and two-year survival rate), toxicity and QOL evaluation
      etc, were discussed. In Regimen A, ER of complete case was 40% (95% CI 20.8
      59.2%) and MST was 9.1 months: responder was 9.8 months and non-responder was 9.1
      months. In Regimen B, ER of complete case was 36.4% (95% CI 22.7-50.1%) and MST
      was 9.1 months: responder was 15.3 months and non-responder was 7.5 months. In
      the evaluation of toxicity and QOL, Regimen B was prominently better than Regimen
      A. The results indicated that after careful consideration of the above-mentioned
      points, good-quality clinical trials must be performed.

PMID- 8279841
TI  - [Strategy for the ovarian cancer treatment].
AB  - The morbidity and mortality rate of ovarian cancer patients are significantly
      inclined recently in Japan. FIGO stage is a powerful prognostic factor, hence
      treatment schedule must be based on precise staging. For stage I patients, total
      abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), partial
      omentectomy (p-OMTX) and appendectomy (APX) are included to standard surgical
      procedure. Adjuvant chemotherapy consisted with CAP (cyclophosphamide,
      adriamycin, cisplatin) or CP is given for 5 courses postoperatively. However,
      those who are stage Ia (grade 1) and desire child bearing could have unilateral
      salpingo-oophorectomy and conserve conceptability. Adjuvant chemotherapy for
      those patients is now on prospective randomized trial in Japan. One arm is 50
      mg/day of cyclophosphamide for 3 months and the other arm is cyclophosphamide 500
      mg/m2 + CDDP 75 mg/m2 every 4 weeks for 3 courses. For stage II or more patients,
      total omentectomy and retroperitoneal lymphadenectomy are added to above
      mentioned procedure. Cisplatin (15.75 mg/m2/week or more) based adjuvant
      chemotherapy is given for 5-10 courses. Therapeutic significance of
      retroperitoneal lymphadenectomy is also under study in patients who are optimally
      debulked (< 2 cm residual tumor). They are randomly divided into two groups:
      lymphadenectomy group and no-lymphadenectomy group. They receive 5 courses of CP
      therapy (cyclophosphamide 600 mg/m2 + CDDP 75 mg/m2) afterwards. Survival rate
      and time to progression are the primary endpoints.

PMID- 8279842
TI  - [Problems of randomized controlled study on surgical adjuvant chemotherapy for
      colorectal cancer in Japan].
AB  - There were many clinical trials to evaluate the significance of surgical adjuvant
      chemotherapy for colorectal cancer, but large-scale randomized controlled study
      was limited in Japan. From results of these trials, the effectiveness of adjuvant
      chemotherapy for colorectal cancer remained controversial. In this paper, I
      described the outline and summarized results of recent randomized controlled
      study carried out by Japan Cancer Chemotherapy Study Group for Colorectal
      Carcinoma and discussed various problems (case registration, ineligible cases,
      statistical method, follow up) of this study.

PMID- 8279843
TI  - [The investigational strategy and present status of hepatic arterial infusion
      chemotherapy for liver metastasis for colorectal cancer].
AB  - The present investigational goal of hepatic arterial infusion chemotherapy for
      liver metastasis from colorectal cancer is to re-evaluate the impact of hepatic
      arterial infusion chemotherapy on survival by a comparative study combined with
      systemic chemotherapy. As an approach to this goal, technical standardization,
      development of an effective regimen without pumps and an improved system of
      cooperative study are being carried out. However, there are many problems to be
      solved in order to perform a randomized trial.

PMID- 8279844
TI  - [Chemotherapy for malignant lymphoma in Western countries and Japan].
AB  - Nationwide epidemiological studies have disclosed that lymphoid malignancies in
      Japan are markedly different from those in Western countries; they are less
      frequent in indolent B-lymphoma and Hodgkin's disease and more frequent in T-cell
      lymphoma, particularly adult T-cell leukemia-lymphoma (ATL). In 1978, the
      Lymphoma Study Group (LSG) of Japan started multicenter clinical trials for
      malignant lymphoma. Since then various kinds of phase II and III studies for
      aggressive lymphoma, Hodgkin's disease, ATL, T-lymphoblastic lymphoma, acute
      lymphoblastic leukemia and multiple myeloma have been conducted by the LSG. Based
      on the results of clinical trials conducted in Western countries and the LSG, the
      state of the art of chemotherapy for malignant lymphoma is described. In
      aggressive lymphoma of advanced stages, after establishment of CHOP therapy (1st
      generation), better results were reported in Western countries for single
      institute phase II studies of non-cross resistant alternating multiagent
      chemotherapy (2nd generation) and high relative dose intensity chemotherapy (3rd
      generation). However, recent multicenter phase III studies, comparing CHOP with
      3rd generation regimens, revealed that CHOP remains the best available treatment,
      because of similar failure-free and overall survival with lower cost and lower
      severe toxicity.

PMID- 8279845
TI  - [State of the art of chemotherapy for adult acute leukemia in Japan].
AB  - For a disease like leukemia with an annual incidence of 3 to 4 per a 100,000
      population, a multicenter cooperative study is essential to develop better
      therapeutic regimens. Our Japan Adult Leukemia Study Group (JALSG) started its
      first multicenter cooperative study in 1987. In the AML 87 study, response
      oriented individualized induction therapy produced 78% complete remissions in 252
      consecutive adult AML, a higher remission rate than that of any multicenter
      studies in the U.S.A. and Europe. For further development of clinical study for
      cancer in Japan, financial support to highly qualified clinical study groups by
      the government is urgently needed.

PMID- 8279846
TI  - [Some proposals to cancer clinical trials in Japan--a biostatistician's view].

PMID- 8279847
TI  - Anecdotal clinical trials of the past.

PMID- 8279848
TI  - Meta-analysis of randomized clinical trials in cancer.

PMID- 8279849
TI  - [Japan Clinical Oncology Group for cooperative cancer clinical trials and role of
      the statistical center in the management of cancer clinical trials].
AB  - In 1978, clinical investigators decided to collaborate on clinical trials through
      a "cooperative group" mechanism in order to promote multidisciplinary treatment
      of cancer under the auspices of a Grant-in-Aid for Cancer Research from the
      Ministry and Health and Welfare. This cooperative study group was formally
      renamed in 1990 and became "The Japan Clinical Oncology Group (JCOG)," and its
      Statistical Center was housed in the National Cancer Center Hospital. This paper
      introduces various JCOG activities and the role of the Statistical Center.

PMID- 8279850
TI  - [Clinical Oncology Groups in Japan: experience of the Japan Adult Leukemia Study
      Group (JALSG)].
AB  - Although Grants-in-Aid of the Ministry of Health and Welfare support a
      considerable number of clinical cancer studies in Japan, there is no established
      clinical oncology group in Japan which is supported by the government or public
      grants. The Japan Adult Leukemia Study Group is a voluntary clinical oncology
      group, established in 1987; it started with 14 institutions and had 45
      institutions as of 1993. Operating funds are donated from each participating
      institution with some help from a Grant-in-Aid of the Ministry of Health and
      Welfare of Japan. Establishment of government-supported nation-wide clinical
      oncology groups is urgently needed for further development of high quality
      clinical cancer studies in Japan.

PMID- 8279851
TI  - [Evaluation of adjuvant immunochemotherapy in advanced gastric cancer].
AB  - Evaluation of adjuvant immunochemotherapy using Polysaccharide K (PSK) for
      advanced gastric cancers was performed by meta-analysis of 6 clinical trials in
      which 5-year survival has been reported in distinguished journals of Japan. The
      odds ratio of 0.75 (95% confidence interval 0.62-0.93, p < 0.01) favored
      immunochemotherapy compared to chemotherapy. In the Chubu district, 3 consecutive
      trials using PSK were performed beginning in 1977. From meta-analysis of the 2
      preceding trials, immunochemotherapy was suggested to be effective in a subgroup
      of T2 and T3 primary tumor, and PPD skin test positive cases. The third trial was
      performed in this group of patients and a statistically significant difference (p
      = 0.044) was observed from the 5-year results.

PMID- 8279852
TI  - [Malignant tumors of the thyroid in 1993].

PMID- 8279853
TI  - [Insular carcinoma of the thyroid. Apropos of a case and review of the
      literature].
AB  - We present a new case report of "Insular" thyroid carcinoma. The first series was
      published, in 1984, by Carcangiu et al. The propensity for local recurrence and
      early distant metastases explains the poor prognosis of this carcinoma and
      demands aggressive therapy at the time of diagnosis. This includes radical
      surgery, radiotherapy with possible chemotherapy. Clinical and pathological
      arguments suggest that this carcinoma could be an intermediate stage in the
      process of loss of differentiation of some thyroid neoplasms.

PMID- 8279854
TI  - [Undifferentiated carcinomas of the thyroid corpus. Apropos of 10 cases].
AB  - Ten undifferentiated thyroid carcinomas detected between 1976 and 1991, were
      reviewed by means of immunohistochemical techniques. These tumors were highly
      aggressive with a mean survival rate of three months after the histological
      diagnosis. They were predominant in women and always occurred in old people (mean
      age 63.1 years). Four tumours were composed of differentiated trabecular areas.
      Another one was included in a microvesicular adenoma and a sixth one occurred as
      a recurrence of a papillary carcinoma surgically treated four months previously.
      Six tumours were cytokeratin-positive and two of them showed a cytokeratin
      vimentin coexpression. These results, like those of an electron microscopic
      analysis of 1 case, confirm the epithelial origin of these tumours.
      Undifferentiated carcinomas must be distinguished from poorly differentiated
      carcinomas and from malignant non Hodgkin lymphomas which have a better prognosis
      and a different therapeutic approach. The immunohistochemistry and the electron
      microscopy are useful to identify undifferentiated thyroid carcinomas.

PMID- 8279855
TI  - [Uterine metastases originating from breast cancer. Apropos of 12 cases].
AB  - The authors report a retrospective clinicopathologic analysis based on 12 cases
      of uterine metastases from breast cancer. The myometrium was more often involved
      than the endometrium, and a metastatic lesion occurred in an interstitial
      leiomyoma in one case. Bilateral ovarian involvement was associated in 11 cases.
      The histopathological type was predominantly represented by invasive lobular
      breast cancer in 10 cases: in this series, 3 subtypes were identified, the solid
      variant (6 cases), the classical variant (2 cases), and the alveolar variant (2
      cases). The steroid receptor status in the tumor specimens was found to be
      constantly positive. The literature concerning the pathologic diagnosis was
      reviewed: most breast cancers metastasizing to the female genital tract and to
      the peritoneal surface appeared to be invasive lobular cancers.

PMID- 8279856
TI  - [Regressive mitochondrial abnormalities in the muscular biopsy of a bicycling
      champion].
AB  - The onset of severe muscle cramps in the course of road racing led a champion to
      undergo a muscle biopsy. Fuscinophilic deposits were detected around muscle cell
      fibers together with a few PAS positive deposits. These findings were related to
      the accumulation of abnormal mitochondria and glycogen granules. The subsequent
      study of the mitochondrial respiratory chain did not reveal any modification and
      so ruled out a genuine mitochondrial myopathy. Such mitochondrial modifications
      are probably related to the onset of muscle cramps, but no metabolic disturbance
      could be found to account for these two phenomena.

PMID- 8279858
TI  - ["Tufted angioma". A benign vascular tumor to differentiate with Kaposi sarcoma].
AB  - Among recently characterized vascular tumors, tufted angioma or angioblastoma is
      a benign acquired slowly progressive cutaneous tumor, which most commonly arises
      in the neck and upper trunk in children and young adults. This case report
      emphasizes the clinical and histological features of tufted angioma. Light
      microscopic examination reveals numerous lobules of closely packed capillaries
      scattered throughout the dermis. Vascular lumina are difficult to define. There
      are no atypical cells. Familiarity with tufted angioma should prevent this lesion
      from being misdiagnosed as malignant vascular tumor arising in young persons,
      especially Kaposi's sarcoma.

PMID- 8279857
TI  - [Intraepithelial lesions of the cervix uteri and human papillomaviruses:
      comparative study of histological data and in situ hybridization. Apropos of a
      series of 77 cervical biopsies].
AB  - Seventy seven biopsy samples of cervical mucosa were tested for the presence of
      human papillomavirus (HPV) by immunohistochemistry and in situ hybridization.
      From the 38 samples identified as condyloma or cervical intraepithelial neoplasia
      (CIN), 31 were positive after in situ hybridization and 14 after immunochemical
      analysis. HPV 6 was found exclusively in condyloma acuminata (2 samples) whereas
      the HPV 16 probe essentially hybridized with high grade intraepithelial lesions
      (CIN II, CIN III). Low grade intraepithelial lesions (flat condyloma, CIN I)
      demonstrated a larger diversity of HPV types (HPV 16, 18, 31, 33). A close
      correlation was demonstrated between the histologic features of lesions and their
      HPV 6 or HPV 31 content but not for other HPV types. HPV 31 containing lesions
      showed a peculiar architecture with numerous, elongated papillae resulting in a
      spiked appearance.

PMID- 8279859
TI  - Papillary carcinoma of the breast. Fine needle aspiration cytology (FNAC) of two
      cases.
AB  - Cytologic findings of two cases of infiltrating papillary carcinoma of the breast
      are presented. Both cases showed highly cellular smears, prominent papillary
      configuration, and cohesive groups of polygonal cells with bland nuclei and
      scarce mitoses. Bipolar cells were not observed. A clean background with
      hemorrhage, lymphocytes and hemosiderin-laden macrophages was also found.
      Histologic sections confirmed the initial diagnosis and proved their infiltrating
      nature. Literature concerning its cytologic differential diagnosis is briefly
      reviewed and commented.

PMID- 8279860
TI  - [Primary malignant histiocytofibroma of the pancreas. Apropos of a case].
AB  - Primary malignant fibrous histiocytoma of the pancreas are rare. To our knowledge
      only 3 cases have been found in the literature. We report a new case of primary
      malignant fibrous histiocytoma of the pancreas in a 72 years old man. Various
      patterns were intermixed in this tumor: storiform, giant-cellular and myxoid
      patterns. After surgical resection, within one year, there were recurrence of the
      tumor and metastasis to the liver resulting in the death of the patient.

PMID- 8279861
TI  - [Endometrioid adenocarcinoma of the uterine isthmus associated with atypical
      endometrial hyperplasia and polycystic ovaries. Apropos of a case with bicornuate
      uterus in a 38 year old woman].
AB  - A 38 year old patient with multiple known risk factors for endometrial carcinoma
      (monophasic cycles, obesity, familial prediabetes, nulliparity, polycystic
      ovaries with diffuse thecal hyperplasia) presented with metrorrhagia caused by an
      endometrial lesion for which the diagnosis hesitated between atypical endometrial
      hyperplasia and carcinoma. Hysterectomy was performed because of the presence of
      a bicornuate uterus, obesity of 130 kg and the patient's lack of desire to have
      children. Examination of the uterus did not reveal any myometrial invasion in
      contact with the hyperplastic endometrium. The discovery of an endometrioid
      carcinomatous metastasis in the lower third of the vagina one year later allowed
      the retrospective detection of a 3 mm endometrioid carcinoma in the isthmus. No
      other metastases or recurrence were observed with a follow-up of 5 years.

PMID- 8279862
TI  - [Soft tissue tumor club].

PMID- 8279863
TI  - [Quality evaluation in cervicovaginal cytology. National program].

PMID- 8279864
TI  - [Tropical biological diversity and therapeutic innovations. Research conducted by
      ORSTOM].

PMID- 8279865
TI  - [Plasmodium prevalence and parasitic burden in blood donors of Brazzaville,
      Congo].
AB  - To assess the frequency of malaria-infected blood donations in Brazzaville
      (Congo) thick films from all blood donors (n = 12,375, minimum per month: 857,
      maximum per month: 1,295; sex ratio: 9.6) at the Brazzaville University Hospital
      were examined quantitatively for Plasmodium (screening threshold: 20/microliters
      of blood) over one year (1989). The overall prevalence rate for all species of
      Plasmodium was 8.5%. It varied according with age but not with sex. P. falciparum
      predominated (92%), followed by P. malariae (7%) and P. ovale (3%). For P.
      falciparum: 1--the prevalence rate was 7.8% but varied over the year from 4.8% in
      August (6.2% for the dry season on the whole) to 11.5% in March (9.6% for the
      rainy season); 2--the parasitic load, also variable according to the season, was
      over 600/microliters in 24% of the cases (i.e. 1.9% of all donations) and over
      6,000/microliters in 15 cases (i.e. 1.6% of the cases). In conclusion the
      proportion of blood donations infected with P. falciparum (with a parasitic load
      > or = 20/microliters) varied in Brazzaville from 6% in the dry season to 10% in
      the rainy season.

PMID- 8279866
TI  - [Long-term effect of a single dose of ivermectin on skin microfilarial density in
      an endemic onchocerciasis area of North Cameroon].
AB  - The long-term efficacy of a single dose of ivermectin (150 micrograms/kg) on skin
      microfilarial densities was evaluated by comparing parasite levels, before and
      after treatment, in 192 patients living in an area endemic for onchocerciasis in
      North Cameroon. A mass treatment with ivermectin has been undertaken in 1989 in
      two villages, where pretreatment community microfilarial loads (CMFL) were 5.5
      and 25.1 microfilariae per snip. The parasitological examination carried out 32
      months later showed that the microfilarial densities in the adults where only 24
      and 51% of the initial values, respectively. In a third village, treated once in
      1989 but located in an area where annual mass distributions of ivermectin have
      been undertaken since 1987, the mean microfilarial density 28 months after
      treatment was only 12% of the initial value. In 1992, the mean microfilarial load
      in children had decreased significantly in comparison with those of 1989 only in
      the village where the level of endemicity was initially the lowest. The rate of
      increase in the number of skin microfilariae after one dose of ivermectin is
      related with the pretreatment endemicity level. The impact of large-scale
      ivermectin treatments on the transmission of onchocerciasis enhances the long
      term efficacy of this drug on the skin microfilarial densities.

PMID- 8279867
TI  - Salivary gland surface carbohydrate variations in three species of the Anopheles
      gambiae complex.
AB  - Fluorescein isothiocyanate (FITC)-conjugated lectins (agglutinins) were employed
      as probes to distinguish between the various carbohydrates present on the surface
      of salivary glands of three species of mosquito of the Anopheles gambiae complex.
      Of twenty lectins tested, eight (Concanavalin A- Con A, Lathyrus odoratus- LOA,
      Lens culinaris, Pisum sativum-PSA, Vicia faba- VFA, Triticum vulgaris, Maclura
      pomifera- MPA and Ulex europaeus) specifically reacted with the salivary gland
      membrane. Both mannosyl and N-acetylglucosamine moieties were detected in the
      three Anopheles gambiae sensu stricto strains, the two An. arabiensis strains and
      a single An. merus strain examined. Variations in the degrees of fluorescent
      intensities of Con A and MPA in particular suggested interspecies differences in
      membrane mannosyl and galactosyl residues on the salivary gland lobes of the
      three mosquito species in this study. Furthermore, intraspecific variations in
      mannose as indicated by Con A, LOA, PSA and VFA staining were demonstrated
      between the An. gambiae s.s. strains. The use of either peroxidase-labelled or
      biotinylated lectins confirmed the binding specificities of the above lectins.
      The consistent differences observed in lectin binding suggest that variations
      occur in salivary gland surface carbohydrate residues and that lectins can be
      used to distinguish between at least some members of the An. gambiae complex.

PMID- 8279868
TI  - Characteristics of HIV/AIDS patients attending a rural hospital in Cameroon.
      Manyemen HIV/AIDS Team.
AB  - Manyemen, a rural community in Cameroon, has now been hit by the HIV epidemic.
      This paper describes the experiences gained at the Presbyterian General Hospital
      in Manyemen between 1990 and 1992 regarding HIV infection in pregnant women, AIDS
      case management, counseling and home visits. A total of 383 pregnant women
      attending antenatal clinics were tested. We found a 2.9% HIV-1 seroprevalence and
      a 17% reactivity to a non-specific syphilis test, rapid plasma reagin, RPR. In
      1990, 1991 and 1992, we diagnosed 55, 89 and 94 cases of clinical AIDS
      respectively. New TB cases seen in the same period showed the following HIV
      positive rates 3.5%, 2.4% and 5.8%. A detailed study of 78 AIDS patients revealed
      that the five most common presenting signs in our patients were wasting (80%),
      prolonged fever (28%), chronic diarrhoea (17%), oropharyngeal candidiasis (14%)
      and pulmonary TB (10%). Pretest and post test counseling is routinely done by the
      AIDS team. About 79% of the patients were post counselled as were 27% of their
      relatives. Home visits have been started. These results show that AIDS is no
      longer an issue confined to cities in Cameroon and that rural hospitals should
      institute a programme, similar to ours, to help them cope with the AIDS epidemic.

PMID- 8279869
TI  - [Continuity of care and treatment of hypertension at a health center in Tunisia].
AB  - This article describes the follow-up of 210 hypertensive patients in Soliman,
      Tunisia. Five years after starting treatment, two thirds of the patients are
      still followed-up. The incidence of interruption of treatment is of 0.18 per year
      of follow-up. Nearly half of these first interruptions occur during the first six
      months, but most do not result in a final abandon of treatment. The drop in blood
      pressure is more important among those who stick to their appointment schedules,
      than among those who do not. The former also present less hypertensive crises.

PMID- 8279870
TI  - An epidemiological study of hemoglobin levels and prevalence of anemia in young
      children from Bas-Zaire.
AB  - A population of 183 Zairean infants and young children (0.5 to 48 months old) who
      lived in rural Bas-Zaire has been examined in regard to hemoglobin (Hb),
      hematocrit (Hct) and mean corpuscular hemoglobin concentration (MCHC). The mean
      Hb was 9.03 g/dL, Hct 28.4%, and MCHC 30.7 micrograms/dL. These means are below
      normal by WHO and/or American Academy of Pediatrics criteria. Although there was
      no significant sex difference in the mean hematoglobin measurements, boys more
      than 24 months old had a higher mean Hb (9.98 g/dL) than girls (8.59d g/L) of the
      same age. Approximately 80%, 76% and 56% of children had Hb < 11 g/dL, Hct < 34%
      and MCHC < 32 micrograms/dL respectively. The highest prevalence of anemia was
      between the age of 12 and 18 months. Severe anemia (Hb < 8 g/dL) was observed in
      30.65% of the study population (26.6% boys and 34.8% girls). Approximately one
      third of children had very low Hct levels (< or = 25%). Based on MCHC, iron
      deficiency was likely responsible of the anemia in 61% of the children. Both Hb
      (p < 0.05) and Hct positively correlated with the mother's level of education.
      Because of the many detrimental effects of iron deficiency in infants and young
      children on immunity, psychomotor, behaviour and mental development routine
      assessment of iron status and correction of iron deficiency should become a part
      of the Surveillance Programme in this population.

PMID- 8279871
TI  - Cost recovery for drugs provided at the rural dispensary: an experiment in Niger.
AB  - An intervention was conducted in 1989-1990 in rural Niger to introduce a cost
      recovery system for the drugs prescribed at the dispensary level. The community
      concerned, about 27,000 persons, chose to pay a fixed fee per episode of illness.
      The fee covered the treatment for a maximum of seven days. The rate was fixed at
      US$ 0.8 per adult and US$ 0.4 per child. The drug prescription was rationalized
      through decisional guidelines including standardized treatments with essential
      drugs. All drugs were bought locally but most of them were commercial brands.
      During the first ten months of intervention, the revenues only covered 51% of the
      drug expenses. Aware of the deficit, the village representatives decided to
      double the fees. As a consequence, the cost recovery rate reached 77%. During the
      low fee period, the utilization of the curative services increased by 80%. When
      the fees were doubled, the attendance steadily declined and tended to reach the
      rate registered before the intervention while the mean cost per case and the
      percentage of costly treatments with antibiotics increased. It can be assumed
      that the increase in fees deterred patients requiring low-cost treatment.

PMID- 8279872
TI  - Cooperative trials in thoracic oncology are important.

PMID- 8279873
TI  - Summary of current cooperative group clinical trials in thoracic malignancies.
      The Thoracic Intergroup.
AB  - Historically, thoracic surgeons have played a pivotal role in the success of
      clinical trials for early-stage thoracic malignancies. This is illustrated by the
      experience of the Veterans Administration Surgical Oncology Group and by the Lung
      Cancer Study Group. Since the dissolution of the Lung Cancer Study Group, the
      other cooperative groups have been unable to complete any large randomized trials
      because of a lack of surgical participation. A group of thoracic surgeons is now
      addressing this problem by unifying research efforts across the cooperative
      groups. The aim of this summary is to disseminate information about those
      efforts, and to encourage the involvement of North American thoracic surgeons in
      current clinical trials.

PMID- 8279874
TI  - Interhospital transport of the patient on extracorporeal cardiopulmonary support.
AB  - Portable extracorporeal cardiopulmonary support systems have enhanced the
      resuscitation and support of moribund patients outside of the operating room
      environment. The literature documents the successful application of emergency
      cardiopulmonary support within the hospital setting. Clinicians have reported the
      use of helicopter and ground ambulance to transport patients requiring
      intraaortic balloon counterpulsation and fixed-wing transport of neonates
      requiring extracorporeal membrane oxygenation. As medical transport capabilities
      extend the sphere of tertiary care to outlying medical facilities, there is a
      role for extracorporeal cardiopulmonary support in the initial stabilization and
      safe transport of critically ill patients, via air or ground ambulance.
      Potentially, the early application of life-sustaining technology can lower
      mortality and morbidity in patients with a survivable pathology. This is a report
      on the experience with the resuscitation and interhospital transport of patients
      on extracorporeal cardiopulmonary support.

PMID- 8279875
TI  - Reconstruction with free jejunal autograft after pharyngolaryngoesophagectomy.
AB  - Twenty-four patients with hypopharyngeal or cervical esophageal carcinoma were
      treated surgically. All had squamous cell carcinoma, and none had intrathoracic
      lymph node involvement by preoperative computed tomography. Endoscopy in 18
      patients confirmed there was no intramural spread into the thoracic esophagus.
      The patients underwent pharyngolaryngoesophagectomy and bilateral modified
      radical neck dissection. Reconstruction of the cervical esophagus was performed
      with transplantation of a free jejunal autograft. Postoperative complications
      included anastomotic leak in 2 patients (8.3%), wound infection in 3 (12.5%), and
      intussusception in 4 (16.7%). Reconstruction of the cervical esophagus was
      successful in 23 (95.8%) of the 24 patients. The operative mortality rate was
      4.2%, and the 5-year survival rate was 39.7%. We emphasize that
      pharyngolaryngoesophagectomy followed by transplantation of a free jejunal graft
      is suitable for cervical esophageal carcinoma or hypopharyngeal carcinoma when
      the disease is limited to the cervical region.

PMID- 8279876
TI  - Postoperative bronchopleural fistula: endoscopic closure in 12 patients.
AB  - Twelve consecutive patients with postresectional bronchopleural fistula were
      treated with endoscopic application of tissue glue adhesive (methyl-2
      cyanoacrylate). Eight patients had associated empyema. Endoscopic gluing was
      successfully accomplished in 10 cases (success rate of 83%). The two failures
      both had fistulas of 0.5 cm or larger. Bronchopleural fistulas developed in 8
      patients early after the intervention (< 15 days): of the 4 patients without
      associated empyema, 3 had their fistula definitely closed after endoscopic
      treatment. Similarly, 3 of the 4 patients with early bronchopleural fistulas and
      empyema were cured after endoscopic closure of the fistula and appropriate
      management of the empyema. Four bronchopleural fistulas occurred late after the
      operation (> 15 days) and all had associated empyema. Successful endoscopic
      closure of the fistula was accomplished in all. Resolution of the empyema
      occurred in 1. We conclude that endoscopic application of tissue adhesive may be
      a valid therapeutic measure in selected patients with postresectional
      bronchopleural fistula. In late bronchopleural fistula with empyema, the closure
      of the fistula can be achieved, but empyema may persist and require additional
      surgical procedures.

PMID- 8279877
TI  - Coronary artery bypass grafting: the Society of Thoracic Surgeons National
      Database experience.
AB  - The need for accurate risk assessment has become an indispensable element in the
      practice of cardiac surgery. The Society of Thoracic Surgeons National Cardiac
      Surgery Database allows subscribing institutions to perform sophisticated patient
      risk assessment using traditional statistical tools and a newly developed risk
      model of operative mortality. The database experience with isolated coronary
      artery bypass grafting has been studied most closely at this point and serves as
      the basis for this report. The approach to operative risk assessment is presented
      along with an analysis of important risk factors in the practice of coronary
      artery surgery from 1980 through 1990. The database contains records of 80,881
      patients undergoing coronary artery bypass grafting in numerous institutions from
      1980 through 1990. These records were used to conduct a detailed analysis of risk
      factors associated with coronary operations in this time interval and to present
      statistical methods used to formulate a risk equation that allows one to predict
      the probability of operative death. In the course of this decade, there were
      clearly defined trends showing a statistically significant increase in adverse
      patient risk factors. The risk model has proven to be a reliable tool for
      predicting the probability of operative death in an individual patient and may be
      valuable in both patient counseling and medical decision making. Large multi
      institutional databases of this type are key ingredients of modern operative risk
      assessment. A database containing a broad national experience of this type can
      represent an aggregate experience that may well approximate a universally
      accepted standard of care.

PMID- 8279878
TI  - Right thoracotomy for reoperative right coronary artery bypass procedures.
AB  - The use of a right thoracotomy is a safe alternative approach for reentering the
      mediastinum for reoperative right coronary artery bypass grafting. This technique
      was used in 9 patients and allowed minimal dissection, reducing the risks of
      hemorrhage and injury to previously placed patent grafts. Cardiopulmonary bypass
      was used in 4 patients in whom myocardial protection was accomplished with
      systemic hypothermia. Right atrial cannulation provided adequate venous return,
      with arterial inflow established via the femoral artery (n = 2) or ascending
      aorta (n = 2). In 5 patients, revascularization was accomplished by temporary
      coronary artery occlusion without cardiopulmonary support. There were no deaths,
      and postoperative recovery was not delayed. Postoperative chest drainage (mean +/
      standard deviation, 1,076 +/- 718 mL) was significantly less (p < 0.01) than
      redo median sternotomy (1,352 +/- 602 mL) in a similar population. Eight of 9
      patients remain free of angina 29 +/- 24.8 months postoperatively.

PMID- 8279879
TI  - Prevention of lung injury during open heart operations for congenital heart
      defects.
AB  - To elucidate free radical-induced lung injury associated with open heart
      operations for congenital heart defects, we studied 23 such patients. Maximum
      plasma chemiluminescence level (a marker of peroxylipids) in patients with
      pulmonary hypertension (n = 8) was higher than in patients with cyanotic disease
      (n = 8) (1,115.4 +/- 189.9 versus 728.8 +/- 48.3 counts; p < 0.05). There was a
      significant correlation between the maximum chemiluminescence level and
      preoperative pulmonary to systemic arterial pressure ratio (r = 0.929; p < 0.05).
      To investigate the effect of allogeneic leukocytes, we compared pulmonary
      hypertensive patients without allogeneic leukocyte transfusion during operation
      (n = 7) with the group with pulmonary hypertension. Both maximum
      chemiluminescence level during bypass (712.4 +/- 24.9 versus 1,115.4 +/- 189.9
      counts; p < 0.05) and percent decrease in pulmonary arterial pressure after
      bypass (44.7% +/- 6.2% versus 28.2% +/- 4.5%; p < 0.05) were significantly
      improved, suggesting that depletion of leukocytes decreased the lung injury
      induced by free radical reaction.

PMID- 8279880
TI  - Airway complications after pulmonary transplantation.
AB  - Airway healing was identified initially as one of the fundamental limitations of
      pulmonary transplantation. Recent experience suggests that this is no longer the
      case. A series of 67 pulmonary transplants (27 heart-lung, 31 single-lung, 9
      double-lung) in 66 patients surviving more than 14 days was reviewed with
      reference to airway complications. There were 75 anastomoses at risk in two
      groups as defined by anastomotic location: 47 anastomoses in 38 patients in a
      bronchial group and 28 anastomoses in 28 patients in a tracheal group. A total of
      10 airway complications developed (stenosis in 5 patients [4 bronchial group, 1
      tracheal group] and dehiscence in 5 patients [1 bronchial group, 4 tracheal
      group]) causing two airway-related deaths (2 of 67) in the series. However, no
      significant correlation could be identified with either ischemic interval, suture
      technique, type of wrap, preoperative or postoperative steroid therapy, or date
      of first rejection episode. Airway complications are no longer a major limitation
      of pulmonary transplantation. Satisfactory airway healing can occur in both the
      presence of steroid therapy and the absence of an omental or pericardial wrap.

PMID- 8279881
TI  - Quantitative gas transfer of an intravascular oxygenator.
AB  - The intravascular oxygenator is a newly developed device for intracaval gas
      exchange in critically ill patients with respiratory failure. In an experimental
      ex vivo model, performance characteristics of the intravascular oxygenator/carbon
      dioxide removal device were studied. With a mean hemoglobin concentration of 6.2
      +/- 1.9 g/dL (mean +/- standard deviation), total O2 transfer was 21.8 +/- 4.8
      mL/min at a blood flow of 1 L/min, 37.0 +/- 12.6 mL/min at 2 L/min, at 2 L/min,
      and 47.5 +/- 16.7 mL/min at 3 L/min. Total CO2 transfer was 27.3 +/- 6.6 mL/min
      at a blood flow of 1 L/min, 38.6 +/- 8.9 mL/min at 2 L/min, and 40.4 +/- 9.3
      mL/min at 3 L/min. In contrast to total gas transfer, O2/CO2 transfer rates
      (mL/L) diminished significantly with increasing blood flow. In addition, there
      was a negative correlation between O2 transfer rate and venous O2 partial
      pressure (r = -0.73; p < 0.0001), a positive correlation between CO2 transfer
      rate and venous CO2 partial pressure (r = 0.65; p < 0.0001), and a positive
      correlation between O2 and CO2 transfer rates and blood hemoglobin level (r =
      0.57 [p < 0.01] and r = 0.70 [p < 0.01], respectively). These results demonstrate
      that the behavior of the intravascular hollow-fiber oxygenator is similar to that
      of the classic membrane oxygenator used for cardiopulmonary bypass: total gas
      transfer correlates directly with blood flow and venous CO2 partial pressure and
      indirectly with venous O2 partial pressure. The O2 and CO2 transfer rates
      increase significantly with increasing hemoglobin content of the blood.

PMID- 8279882
TI  - Changes in left ventricular performance after global ischemia: assessing LV
      pressure-volume relationship.
AB  - To determine the effect of ischemia and reperfusion on left ventricular systolic
      function, we studied the ischemia-induced rightward shift of the ventricular
      pressure-volume relationship. Eight mongrel dogs were intubated, and their hearts
      were exposed through a thoracotomy. A conductance catheter and micromanometer
      were used to obtain instantaneous left ventricular pressure-volume data. The dogs
      were subjected to 20 minutes of normothermic global myocardial ischemia, followed
      by 80 minutes of reperfusion under total cardiopulmonary bypass. Data were
      acquired during transient (10- to 12-second) periods of acute volume loading
      before ischemia and at 20-minute intervals during reperfusion as bypass was
      continued. The relationship between stroke work and end-diastolic volume (ie,
      preload recruitable stroke work [PRSW]) and the end-systolic pressure-volume
      relationship were highly linear throughout the study (mean r = 0.954 to 0.983 for
      PRSW; mean r = 0.954 to 0.984 for end-systolic pressure-volume relationship).
      Ischemia produced changes in the PRSW: (1) the slope decreased significantly at
      20 minutes and 40 minutes of reperfusion then returned to preischemic levels at
      60 minutes and 80 minutes, and (2) the x-intercept increased significantly up to
      60 minutes. The preload recruitable work area (the area under the linear
      regression line of PRSW) reflected changes in both slope and x-intercept of PRSW
      and was significantly decreased throughout the 80 minutes of reperfusion despite
      gradual recovery. The slope and the x-intercept of the end-systolic pressure
      volume relationship did not change after ischemia.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8279883
TI  - Induction of heat-shock proteins enhances myocardial and endothelial functional
      recovery after prolonged cardioplegic arrest.
AB  - The aim of this study was to investigate the role of heat-shock proteins after
      heat-shock stress on the post-ischemic recovery of cardiac mechanical and
      endothelial function following a prolonged cardiac arrest. Isolated working rat
      hearts were subjected to a cardioplegic arrest for 4 hours at 4 degrees C. Three
      groups (n = 8 in each) were studied: (1) control, (2) sham-treated, and (3) heat
      shocked rats. Postischemic recovery of cardiac output and endothelial function
      (as percent of preischemic control values) was 57.8% +/- 2.8% and 20.8% +/- 3.9%
      in group 1, 50.9% +/- 4.0% and 26.3% +/- 5.9% in group 2, and 74.0% +/- 2.4% and
      51.2% +/- 8.0% in group 3, respectively. Both postischemic myocardial and
      endothelial function were improved by heat stress.

PMID- 8279884
TI  - Cost-effectiveness of preoperative autologous donation in coronary artery bypass
      grafting.
AB  - Concern about the safety of the allogeneic blood supply has made preoperative
      autologous blood donation (PAD) routine before major noncardiac operations.
      However, the costs and benefits of PAD in elective coronary artery bypass
      grafting (CABG) are not well established. We used decision analysis to (1)
      calculate the cost-effectiveness of PAD in CABG, expressed as cost per year of
      life saved, and (2) compare the health benefits of reducing allogeneic
      transfusions with the potential risks of autologous blood donation by patients
      with coronary artery disease. A prospective study of 18 institutions provided
      data on transfusion practice and blood product costs in CABG. On average, PAD in
      CABG costs $508,000 to $909,000 per quality-adjusted year of life saved,
      depending on the number of units donated. Preoperative autologous blood donation
      is more cost-effective (as low as $518,000 per year of life saved) when targeted
      to younger patients undergoing CABG at centers with high transfusion rates. The
      cost-effectiveness of PAD is strongly dependent on estimates of posttransfusion
      hepatitis incidence, but less so on plausible estimates of the current risk of
      human immunodeficiency virus transmission. Although the actual risk of PAD is
      uncertain, even a small fatality risk (> 1 per 101,000 donations) associated with
      blood donation by patients awaiting CABG negates all life expectancy benefits of
      PAD. At current costs, PAD by patients awaiting CABG is not cost-effective,
      producing small health benefits at high societal cost. For the individual
      patient, the risk of donating blood before CABG may well outweigh the benefits
      associated with fewer allogeneic transfusions.

PMID- 8279885
TI  - Early and intermediate results of the Fontan procedure at moderately high
      altitude.
AB  - At higher elevations, alveolar hypoxia increases pulmonary vascular resistance
      and may limit the cardiac output of individuals without a subpulmonary ventricle.
      Thus, we reviewed the outcome of definitive palliation for tricuspid atresia and
      other forms of single ventricle in 60 consecutive Fontan patients living at a
      mean elevation of 1,370 m (range, 910 to 2,130 m). There were four early deaths
      (6.7%; 70% confidence limits, 4.1% to 10.7%) and six late deaths. Kaplan-Meier
      actuarial survival (+/- standard error) is 79.6% +/- 8.2% at 5 years. Survival
      was significantly decreased in patients with a preoperative mean pulmonary
      arterial pressure greater than or equal to 15 mm Hg unless the Fontan procedure
      was performed with a residual fenestration. Exercise tolerance was significantly
      worse at higher elevations in a subgroup of patients who have traveled to
      altitudes of 1,680 to 3,350 m. We conclude that the early and intermediate
      results of the Fontan procedure at moderately high altitude are similar to
      results reported at sea level. However, exercise tolerance may be impaired at
      higher elevations in many patients.

PMID- 8279886
TI  - Effect of magnesium and calcium on myocardial protection by cardioplegic
      solutions.
AB  - The cardioprotective effect of the magnesium and calcium content of hyperkalemic
      cardioplegic solutions was investigated using isolated rat hearts subjected to
      hypothermic ischemic arrest. Hearts were arrested for 180 minutes at 20 degrees C
      by administering a 3-minute infusion of cardioplegic solution containing various
      concentrations of magnesium and calcium. Treatment groups received solution with
      either 0, 8, or 16 mmol/L magnesium. For each of these magnesium concentrations,
      0.1, 0.6, or 1.2 mmol/L calcium was also present in the solution. At each
      concentration of magnesium, the percentage recovery of aortic flow was dependent
      on the calcium concentration. The maximum percentage recovery of aortic flow was
      67.9% +/- 2.3% (mean +/- standard error of the mean) in the Mg-free, 0.1 mmol/L
      Ca group, whereas it was 65.1% +/- 2.7% in the 8 mmol/L Mg, 0.1 mmol/L Ca group
      and 70.0% +/- 3.5% in the 16 mmol/L Mg, 0.6 mmol/L Ca group. No significant
      differences in the recovery of cardiac function and creatine kinase leakage were
      observed between the three groups. The findings suggested that the
      cardioprotective effect was dependent on the relative concentration of both
      magnesium and calcium, and that it is important to maintain an appropriate ionic
      balance in cardioplegic solutions.

PMID- 8279887
TI  - Right ventricular function early after total or standard orthotopic heart
      transplantation.
AB  - Right ventricular failure after orthotopic heart transplantation (OHT) is
      classically related to preoperative pulmonary hypertension. However, the role of
      the enlarged atria in right ventricular dysfunction after OHT remains unclear.
      For that purpose, the right ventricular function in the first 2 days after OHT
      was compared in two groups of transplant recipients: 11 patients who underwent
      standard OHT (group I) and 9 patients who underwent total OHT, which consisted of
      total excision of both the left and right atria and OHT of an intact donor heart
      with its atria as well as its ventricle (group II). Right ventricular ejection
      fraction, cardiac index, and right-sided pressures were recorded at baseline and
      4, 8, 12, 24, and 48 hours after OHT using a Swan-Ganz catheter with a rapid
      response thermistor. Right ventricular function parameters did not differ between
      groups; they were characterized by a decrease in right ventricular ejection
      fraction and an increase in right ventricular end-diastolic volume index whereas
      cardiac index and right-sided pressures remained normal or slightly increased.
      Ischemic time (177 +/- 41 minutes in group I versus 178 +/- 39 minutes in group
      II) and preoperative pulmonary vascular resistance (1.9 +/- 0.7 Wood units in
      group I versus 3.0 +/- 1.5 Wood units in group II) were not different between
      groups. These results suggest that the anatomic and physiologic advantages
      offered by the modified technique of OHT had no clinical relevance in this group
      of patients with low preoperative pulmonary vascular resistances when compared
      with a group of patients who underwent transplantation with the standard
      technique.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279888
TI  - Surgical treatment of lung cancer in the octogenarian.
AB  - The purpose of this study was to investigate the value of surgical treatment for
      lung cancer in the octogenarian. Thirty-three patients 80 years of age or older
      (mean age, 82.4; range, 80 to 92 years; 25 men, 8 women) underwent surgical
      resection in our units between 1974 and 1991. The operative mortality rate was
      3%, and the 5-year survival rate was 32%. The relative 5-year survival rate
      (survival rate of our subjects/that of matched population) was 61%. The mortality
      and long-term survival rates were similar to those in younger patients. In this
      study, long-term survival had no significant dependence on stage of disease,
      histologic tumor type, or complete versus incomplete resection. It was dependent
      mainly on postoperative complications, in particular, cardiorespiratory
      complications (cardiac complications, p = 0.0005; respiratory complications, p <
      0.05). These data suggest that the octogenarian who suffers from lung cancer
      deserves the opportunity for a cure and the long-term benefits of surgical
      treatment, on the condition that no postoperative major cardiorespiratory
      complications set in.

PMID- 8279889
TI  - Transcervical thymectomy for myasthenia gravis.
AB  - The use of transcervical thymectomy in the treatment of myasthenia gravis remains
      controversial. We retrospectively reviewed our experience with this procedure to
      determine its usefulness in the management of myasthenia gravis. Fifty-three
      selected myasthenic patients without thymoma underwent transcervical thymectomy
      between 1977 and 1991. The mean age (27.5 +/- 1.5 years), duration of symptoms (2
      +/- 1.0 years), and preoperative Osserman classification (13% class I, 53% class
      IIA, 28% class IIB, 6% class III) were consistent with previous reports. The
      average hospitalization was 3.0 +/- 0.3 days, but has been 1.6 +/- 0.2 days since
      1987 (n = 14). There were no deaths, and no patients required mechanical
      ventilation for more than 24 hours. Average follow-up was 4.3 +/- 0.4 years with
      a range of 0 to 13 years. Eighty-one percent of patients are symptom free, and 9
      of 21 (43%) are in complete remission at least 5 years postoperatively. One
      patient required a transsternal exploration for worsening symptoms. Clinical
      improvement continued over an extended period of time, and a statistically
      significant decrease in symptoms was evident comparing the first and sixth
      postoperative years. Patients were more likely to be improved or in remission if
      thymectomy was performed within the first year of the onset of symptoms (p <
      0.05). Osserman classification, thymus histology, and patient age were not
      prognostic indicators. Transcervical thymectomy is effective surgical therapy for
      myasthenia gravis in selected patients without thymoma.

PMID- 8279890
TI  - Combined radiosurgical treatment of Pancoast tumor.
AB  - Operative technique and long-term results of 60 consecutive patients with
      Pancoast tumor treated with combined radiosurgical treatment were evaluated.
      External radiation therapy was administered preoperatively in a dose of 30 Gy in
      50 patients. Operation was considered radical (R0) in 36 patients (60%). A
      microscopic invasion of the margin of resection (R1) was observed in 5 patients
      (8.3%). In 19 patients (31.6%) the operation was considered presumably not
      radical (R2). Three patients died in the postoperative period (5%). Fourteen
      major postoperative complications occurred in 13 patients (21%). Seven patients
      had recurrence of pain postoperatively. Overall 3- and 5-year actuarial survival
      rates were 34% and 17.4%, respectively. The corresponding figures for the R0 and
      combined R1-R2 groups were 45.8% and 23.5% (R0), and 11.4% (R1-R2; no 5-year
      survivors were observed in this group) (p < 0.025). Median survivals in the R0
      and combined R1-R2 patients were 19 and 7 months, respectively. Different median
      survivals for the patients with residual tumor were as follows: intervertebral
      foramina, 5 months; subclavian artery (isolated), 9 months; subclavian artery (in
      association), 7 months; brachial plexus, 4 months; and vertebral body, 7 months.
      We conclude that combined radiosurgical treatment represents a valuable
      therapeutic option in the treatment of Pancoast tumor. In case of residual tumor
      a poor outcome may usually be anticipated, but in the majority of these patients
      the operation permits good control of the pain.

PMID- 8279891
TI  - The Society of Thoracic Surgeons National Database status report.
AB  - This report describes the development of the first known national surgical
      database designed for the practicing community cardiothoracic surgeon. Acceptance
      by members of The Society of Thoracic Surgeons has been gratifying. The number of
      patients on the system has grown from 116,109 at the end of 1991 to an
      anticipated 350,000 to 450,000 by the end of 1993. At the time of this report,
      842 surgeons were participating, and more than 1,200 will be on the system by the
      end of 1993. A risk stratification system has been incorporated into the
      software, which predicts each patient's risk based on the individual surgeon's
      past experience. Trend analyses demonstrate a substantial increase in the number
      of patients at increased risk for perioperative death for coronary artery bypass
      operations over the past 5 years, while observed mortality has remained
      relatively constant. Programs are available for adult and congenital heart
      disease, lung cancer, and esophageal cancer, and modules for mediastinal tumors,
      pleural disorders, and benign pulmonary disease will soon be added. We anticipate
      that growth will continue as the need for practice profile data increases because
      of reimbursement issues.

PMID- 8279892
TI  - Potential ablation of accessory atrioventricular pathways: injection of alcohol
      into the atrioventricular groove.
AB  - Accessory atrioventricular (AV) pathways responsible for the Wolff-Parkinson
      White syndrome have been treated successfully by surgical and radiofrequency
      catheter ablation techniques. In this study, we explored the feasibility of
      permanent chemical ablation of accessory pathways by direct injection of 100%
      ethanol into the canine AV groove. Right coronary artery blood flow and AV
      compartment pressure were measured in 5 adult mongrel dogs (part I) during
      injection of saline solution (10 to 15 mL) into the right AV groove.
      Atrioventricular groove compartment pressure increased from 1 +/- 1 to 31 +/- 12
      mm Hg (p < 0.0001) and right coronary artery blood flow increased slightly from
      117 +/- 17 to 138 +/- 44 mL/min (p = not significant). In 8 additional dogs (part
      II), 100% ethanol (10 mL) was injected into the left AV groove. After 6 weeks (n
      = 6) or 12 weeks (n = 2), histologic examination of the left AV groove
      demonstrated localized fibrous replacement of injured epicardial muscle, with
      only scant inflammatory infiltrate. Mild intimal fibrosis and intimal
      proliferation were present in the circumflex artery and its larger branches, but
      no significant luminal narrowing was evident. Angiograms at 12 weeks (n = 2)
      demonstrated no significant narrowing of the circumflex artery. In summary,
      injection of 100% ethanol into the AV groove is capable of locally ablating
      myocardial tissue, presumably including conductive tissues, while sparing the
      coronary arteries.

PMID- 8279893
TI  - "Spontaneous" mediastinal pancreatic pseudocyst fistulization to the esophagus.
AB  - Transhiatal extension of pancreatic pseudocysts is an infrequent cause of
      symptomatic mass lesions in the posterior and middle mediastinum. Delayed
      recognition is common. An alcoholic patient with spontaneous fistulization
      between a mediastinal pseudocyst and distal esophagus is presented.

PMID- 8279894
TI  - Heart-lung transplantation in a patient with pulmonary atresia and ventricular
      septal defect.
AB  - Operation for pulmonary atresia and ventricular septal defect is challenging, as
      in most patients the pulmonary arteries are hypoplastic, nonconfluent, or in part
      absent. In these cases, combined heart-lung transplantation may be the surgical
      treatment of choice. In the described case, the morphology of pulmonary atresia
      and ventricular septal defect was present in combination with completely atretic
      main, left, and right pulmonary arteries. In this patient, successful heart-lung
      transplantation was performed.

PMID- 8279895
TI  - Staged approach to combined repair of pectus excavatum and lesions of the heart.
AB  - The combined repair of severe pectus excavatum and cardiac lesions remains
      technically difficult. We report our experience with a patient undergoing such a
      combined repair of pectus and implantation of an aortic valved conduit in the
      setting of the Marfan syndrome. The procedure was staged such that the dissection
      and bony mobilization was done at the first procedure before heparin
      administration in combination with a sternal split and subsequent aortic repair.
      The second stage of sternal repositioning and cartilage resection was completed
      several days later with excellent cardiopulmonary and cosmetic results. The
      technique and a review of the literature are included.

PMID- 8279896
TI  - Chronic myelogenous leukemia after lymphoid irradiation and heart
      transplantation.
AB  - We have previously reported a case of recurrent cardiac rejection in a heart
      transplant recipient successfully treated with total lymphoid irradiation. Five
      years after transplantation chronic myelogenous leukemia was diagnosed in this
      patient. The long-term effects of total lymphoid irradiation in the heart
      transplant population have not been reported. Based on the known relationships
      among irradiation, gene translocations, and leukemia, we postulate that this
      patient's chronic myelogenous leukemia may be a long-term sequela of previous
      total lymphoid irradiation.

PMID- 8279897
TI  - Acquired immunodeficiency syndrome-related lymphoma of the lung presenting as
      empyema thoracis.
AB  - B-cell lymphoma in patients infected with the human immunodeficiency virus is
      usually a disseminated process that occasionally involves the lungs. Surgical
      diagnosis is often necessary to distinguish this from other neoplasms or
      opportunistic infections of the lung. We report a case of pulmonary B-cell
      lymphoma in a patient infected with human immunodeficiency virus who presented
      with a left empyema thoracis and an associated left lower lobe abscess secondary
      to bronchial obstruction. Resection was performed and the patient subsequently
      recovered from the acute process and survived an additional 6 months. This report
      demonstrates that surgical intervention may be necessary for both the diagnosis
      of pulmonary lymphoma and the definitive management of infectious complications
      that may arise as a result of pulmonary neoplastic disease in patients with
      acquired immunodeficiency syndrome.

PMID- 8279898
TI  - Bilateral pulmonary lobe transplantation: left lower and right middle and lower
      lobes.
AB  - It is difficult to find lungs of appropriate size for double-lung transplantation
      in teenagers and small adults. Nevertheless, many young patients suffering from
      cystic fibrosis are waiting for lung transplantation. We have performed two
      bilateral lobar transplantations (left lower lobe plus right middle and lower
      lobe) with good recovery. Details of the technique are described.

PMID- 8279899
TI  - Cardiac transplantation after donor mitral valve commissurotomy.
AB  - Cardiac transplantation has become a relatively common procedure, with its
      limiting factor being the lack of donor hearts. The donor pool can potentially be
      increased by reevaluating donor criteria and performing innovative procedures on
      the donor heart, such as coronary bypass and valve repair. We present a recent
      case of donor heart mitral valve commissurotomy with successful transplantation.

PMID- 8279900
TI  - Primary leiomyosarcoma of the pulmonary artery: diagnostic and surgical
      implications.
AB  - Primary pulmonary trunk sarcoma is a rare and highly lethal disease. A case of
      multicentric pulmonary trunk leiomyosarcoma with right and left main pulmonary
      artery involvement, mimicking massive pulmonary embolism, is described. The
      importance of a timely diagnosis and of radical surgical excision is discussed.

PMID- 8279901
TI  - Fibrous skeleton endocarditis: repair using Konno procedure.
AB  - Information about the surgical management of fibrous skeleton endocarditis is
      incomplete, as the vast majority of current literature describes the isolated
      repair of either the aortic or the mitral annulus, the combination rarely being
      addressed. Annular destruction, in the presence of endocarditis, demands extreme
      ingenuity for surgical treatment and cure. We describe and illustrate the Konno
      procedure for replacement of both infected mitral and aortic valves and repair of
      mycotic ventricular septal defects.

PMID- 8279902
TI  - Surgical management of left main coronary artery aneurysm.
AB  - To date only 7 patients with left main coronary artery aneurysm associated with
      atherosclerosis have undergone surgical treatment. This report reviews a case of
      atherosclerotic aneurysm of the left main coronary artery with concurrent
      stenotic coronary artery disease that was successfully treated by direct approach
      to the left main coronary artery aneurysm and establishment of coronary artery
      bypass grafts.

PMID- 8279903
TI  - Replacement of a prosthetic valve after the Bentall procedure.
AB  - Patients undergoing a composite graft replacement of the aortic root with
      reimplantation of the coronary ostia (Bentall procedure) are at risk for late
      prosthetic heart valve dysfunction: approximately 10% of the patients are
      expected to experience this complication at 10 years. Therefore, replacement of
      the prosthetic valve is indicated. This procedure involves technical problems
      related to the manipulation and the reconstruction of the composite graft without
      distortion of the coronary arteries. We describe a simple surgical approach to
      treat these particular patients.

PMID- 8279904
TI  - Spontaneous thrombosis in a coronary artery fistula with aneurysmal dilatation of
      the sinus of Valsalva.
AB  - This case report describes spontaneous thrombosis of a congenital coronary artery
      fistula with associated aneurysmal dilatation of the right coronary sinus of
      Valsalva. The grossly dilated sinus of Valsalva was reconstructed with a Dacron
      patch. Coronary revascularization was performed with a sequential saphenous vein
      graft anastomosed to the right posterior descending and posterior ventricular
      arteries distally and to the aorta proximally.

PMID- 8279905
TI  - Oblique wedge osteotomy for correction of asymmetric pectus excavatum in young
      children.
AB  - The procedure modified by Ravitch is usually used to correct pectus excavatum.
      Young children with asymmetric sternal depression need more modification of the
      procedure to maintain the sternum in the elevated flat position. In this report
      we describe a modification of the sternal elevation procedure, including an
      oblique wedge osteotomy through the anterior table, to correct the asymmetric
      sternal depression in young children.

PMID- 8279906
TI  - Simple method for determining proper length of artificial chordae in mitral valve
      repair.
AB  - A simple method for determining the length of artificial chordae in mitral
      reconstructive operations is described. A small tourniquet is used for fine
      adjustment of the length of polytetrafluoroethylene stitches before tying them
      during leaking test. We have used this technique in 10 consecutive patients with
      anterior mitral leaflet prolapse since August 1992. Intraoperative
      transesophageal echocardiography revealed no or only trace mitral regurgitation
      after valve repair in all cases. This method minimized the time of determining
      the proper length of artificial chordae and achieved good results.

PMID- 8279907
TI  - Mesh tube-calibrated varicose veins for coronary artery bypass grafting.
AB  - Complex arterial bypass grafting may be contraindicated for patients with
      multivessel disease and inadequate saphenous veins. In such cases varicose veins
      may be used as bypass conduits after calibration by insertion into mesh tubes.
      After in vitro and experimental testing, as well as gratifying results in
      infrainguinal arterial reconstructions, wrapped varicose vein grafts in addition
      to arterial bypass grafts were used in 6 patients undergoing coronary artery
      bypass grafting.

PMID- 8279908
TI  - Adjuncts to reduce the incidence of embolic brain injury during operations on the
      aortic arch.
AB  - Two adjunctive techniques for operations involving the aortic arch, retrograde
      perfusion of cold oxygenated blood through the superior vena cava and
      establishment of antegrade flow after hypothermic circulatory arrest, are
      described. These techniques should reduce or possibly eliminate the embolization
      of air and particulate matter into the cerebral circulation and may reduce the
      incidence of brain injury.

PMID- 8279909
TI  - The ductus and the coarctation.
AB  - After Robert E. Gross' historic ligation of a persistent ductus arteriosus in
      August 1938, it took 6 years before the first coarctation was operated on. Gross
      initiated experimental procedures directed at repair of coarctation even before
      the ductal operation had been performed. He had the desire, the drive, and the
      determination. Why the delay that allowed Clarence Crafoord to perform the first
      coarctation repair in October 1944?

PMID- 8279910
TI  - Anterior and middle mediastinum paraganglioma: complete resection is the
      treatment of choice.
AB  - Paraganglioma of the mediastinum is described to be an indolent and slow-growing
      tumor. After a patient presented to our center, we reviewed the world literature
      to evaluate the prognosis of this tumor. This review showed that paragangliomas
      are locally invasive and have a high local recurrence rate (44/79 or 55.7%) with
      a true metastatic capacity (21/79 or 26.6%). The overall survival is 62.0%
      (49/79), but only 36.7% (29/79) of patients could be considered as free of
      disease, with survival time of 98.2 +/- 11.7 months (mean +/- standard error).
      The survival with a complete resection is 84.6% (125.7 +/- 18.7 months) versus
      50.0% (71.5 +/- 13.8 months) for patients with a biopsy or a partial excision and
      adjuvant treatment (p < 0.01). We acknowledge the limitation of this
      retrospective study, but a prospective trial is not possible because of the
      rarity of the tumor. We want to emphasize that paraganglioma of the anterior and
      middle mediastinum is an aggressive tumor, and complete surgical resection, using
      cardiopulmonary bypass if necessary, is highly recommended.

PMID- 8279911
TI  - Surgical treatment of tetralogy of Fallot and pulmonary atresia with ventricular
      septal defect.

PMID- 8279912
TI  - 1993: Effects of University of Wisconsin solution on endothelium-dependent
      coronary artery relaxation in the rat. Updated in 1994.

PMID- 8279913
TI  - Graduate training in thoracic surgery.

PMID- 8279914
TI  - Pericardial angiosarcoma and associated hemorrhage.

PMID- 8279916
TI  - Barrett's esophagus.

PMID- 8279915
TI  - About the surgical treatment of pulmonary mycetoma.

PMID- 8279917
TI  - Role of the gut in the development of multiple organ dysfunction.

PMID- 8279918
TI  - Chronic mechanical circulatory support: rehabilitation, low morbidity, and
      superior survival.
AB  - Because of donor scarcity, 12 (39%) of a series of 31 Novacor left ventricular
      assist system recipients required mechanical circulatory support for an average
      of 125 days before transplantation (range, 61 to 303 days). Ten received a heart
      transplant and all survived to discharge. Two died of infection before
      transplantation after 93 and 303 days of support. Significant reductions were
      noted from preimplantation values of right and left cardiac filling pressures.
      Right ventricular ejection fraction and cardiac index increased. The 4-month
      actuarial freedom from infection during support was 75%. Three patients benefited
      from chronic outpatient housing for 5, 18, and 131 days, respectively, with
      improvements in quality of life measures. Ten chronically supported patients
      participated in an intensive rehabilitative exercise program resulting in an
      improvement of New York Heart Association class from IV to I in 9 patients. Mean
      oxygen consumption, which was 10 mL.kg-1.min-1 30 days after implantation (mean
      exercise time, 10 minutes) had risen to 15 mL.kg-1.min-1 before transplantation
      (mean exercise time, 16 minutes). This series suggests that long-term circulatory
      support is compatible with low morbidity, significant physical and hemodynamic
      rehabilitation, and an outpatient setting.

PMID- 8279919
TI  - Comparison of the hormonal response after bidirectional Glenn and Fontan
      procedures.
AB  - Fluid retention is a frequent complication after the bidirectional Glenn and
      Fontan procedures. It was our hypothesis that this fluid retention may have a
      hormonal basis. To test this hypothesis, we made serial determinations of
      antidiuretic hormone, cortisol, aldosterone, angiotensin, and renin before and
      after operation in patients undergoing a bidirectional Glenn (n = 15) or Fontan
      (n = 18) procedure. Patients undergoing a bidirectional Glenn procedure had
      elevations in antidiuretic hormone, cortisol, and aldosterone immediately after
      operation. However, none of the hormonal elevations persisted by the fifth
      postoperative day. In contrast, patients undergoing a Fontan procedure had
      elevations in antidiuretic hormone, cortisol, aldosterone, renin, and angiotensin
      II in the immediate postoperative period. Five days postoperatively, the renin
      and angiotensin II levels remained elevated compared with the preoperative
      values. The data demonstrate that patients undergoing a bidirectional Glenn
      procedure and those undergoing a Fontan procedure have different patterns of
      hormonal response. These results suggest that hormonal factors may contribute to
      fluid retention after these operations.

PMID- 8279920
TI  - First publications from the Society of Thoracic Surgeons National Database.

PMID- 8279921
TI  - Regional deep hypothermia of the spinal cord protects against ischemic injury
      during thoracic aortic cross-clamping.
AB  - We tested in pigs the hypothesis that regional deep hypothermia of the spinal
      cord achieved by cerebrospinal fluid cooling will protect against ischemic injury
      during thoracic aortic cross-clamping. Eight control animals underwent aortic
      cross-clamping at the distal aortic arch and just above the diaphragm for 30
      minutes. Eight experimental animals had placement of two subarachnoid perfusion
      catheters through laminectomies at T4 and the lower lumbar region. The
      subarachnoid space was perfused with normal saline solution at 6 degrees C
      delivered by gravity infusion, with infusion rates adjusted to maintain cord
      temperatures at less than 20 degrees C. After 30 minutes of aortic cross
      clamping, the infusion was stopped and the cord allowed to warm to body
      temperature. Hind limb neurologic function was graded by Tarlov's scale. All of
      the animals in the control group had complete hind limb paraplegia (Tarlov grade
      0) postoperatively. Seven of the 8 animals in the experimental group had
      preservation of hind limb motor function (Tarlov grade 2), and 1 animal had
      complete hind limb paraplegia (Tarlov grade 0) (p = 0.002, Fisher's exact test).
      We conclude that regional deep hypothermia of the spinal cord in pigs does
      provide some protection from ischemic injury during thoracic aortic cross
      clamping. Clinically this may be a useful adjunct for prevention of paraplegia
      during thoracic aortic operations.

PMID- 8279922
TI  - Development of tolerance to experimental cardiac allografts in utero.
AB  - "Actively acquired tolerance" to foreign cells was described in 1953 by Medawar
      and colleagues and formed the basis for subsequent efforts in organ
      transplantation. We have applied these historic principles of intrauterine immune
      manipulation in a vascularized cardiac allograft model. Allogeneic Lewis-Brown
      Norway (LBN) splenocytes (0 to 5 x 10(7) cells) were injected intraperitoneally
      into each fetus of a pregnant Lewis rat at day 14 to 16 of gestation, when T
      cells are "educated" to distinguish self from foreign. This manipulation causes
      fetal attrition inversely proportional to the number of cells injected.
      Heterotopic transplantation using an LBN heart was carried out in each surviving
      fetus at 6 to 8 weeks of age. Untreated Lewis rats rejected LBN hearts within 7.6
      days. Rats receiving LBN splenocytes in utero demonstrated prolongation of graft
      survival proportional to the number of cells given. Surviving animals exposed to
      5 x 10(7) allogeneic cells in utero (n = 4) had graft survivals of 24 to more
      than 150 days (mean, 88.0 days), significantly longer than control animals (6 to
      10 days; mean, 7.6 days; p < 0.02). Significant prolongation of cardiac allograft
      survival and in some cases complete tolerance can be achieved by intrauterine
      exposure to allogeneic cells at a critical period of immunologic development.
      Because many serious cardiac defects amenable to treatment by cardiac
      transplantation can be detected by ultrasound early in gestation, treatment based
      on this strategy may become useful in pediatric heart transplantation.

PMID- 8279923
TI  - Cardiac allografts from high-risk donors: excellent clinical results.
AB  - Rising waiting list mortality and increasing demand for donor organs have led to
      extension of traditionally accepted criteria for evaluation of cardiac grafts.
      From December 1985 to June 1992, 188 cardiac grafts were orthotopically
      transplanted into 178 recipients. Of these grafts, 38.3% (72/188) were defined as
      high-risk donors. Risk criteria included prolonged cardiopulmonary resuscitation,
      age greater than 40 years, high inotrope requirements, undersizing by more than
      20% body weight, significant wall motion impairment by echocardiography,
      elevation of myocardial enzyme levels, and cold ischemia time greater than 4
      hours. There were no recipient deaths attributable to primary graft failure in
      the perioperative period. Operative (30-day), 1-year and 5-year survival was
      95.5%, 86.1%, and 77.3%, respectively, in the high-risk group compared with
      93.7%, 86.0%, and 67.2%, respectively, in the low-risk donor cohort (p = 0.94).
      Comparison of duration of postoperative inotrope use, intensive care unit stay,
      total hospital stay, and in-hospital costs revealed no significant trends
      favoring either group in postoperative morbidity. Among long-term survivors,
      development of graft coronary disease was noted in 47.1% (24/51) of the high-risk
      donor group and only 17.4% (12/69) of the remaining group (p = 0.0005). Left
      ventricular ejection fractions in the high risk donor group were 0.58 +/- 0.01 at
      2 years. Review of this series suggests that selective use of apparently
      compromised cardiac donors is compatible with excellent cardiac function and
      survival. Higher incidence of graft vasculopathy may cause significant morbidity
      during late follow-up.

PMID- 8279924
TI  - Novel technique for extending the use of allografts in cardiac operations.
AB  - Small cryopreserved allografts for use in neonates and infants are increasingly
      difficult to find. We describe a technique for surgically reducing the size of
      the more readily available large-diameter allografts to make them conform to size
      requirements appropriate for neonates and infants. This technique involves a
      longitudinal incision of the allograft from its muscular annulus to its distal
      orifice with the excision of a single valve leaflet. The two commissural posts of
      the excised leaflet and the wall of the allograft are then reapproximated with
      fine suture. Four patients ranging in age from 14 days to 11 months (mean age,
      5.2 months) and ranging in weight from 3 to 8.4 kg (mean weight, 5.2 kg)
      underwent reconstruction of the right ventricular outflow tract using this
      surgical technique. Two patients underwent repair of truncus arteriosus (age, 14
      days and 16 days) and two patients underwent Rastelli operations (age, 9 months
      and 11 months). The mean follow-up time was 22.5 months (range, 14 to 28 months).
      All 4 patients are alive and well. One patient requires digoxin and furosemide
      for moderate quadricuspid truncal valve insufficiency. Serial echocardiography
      documents mild allograft stenosis in 2 patients and trivial to mild allograft
      insufficiency in 2 patients. Because handling characteristics and lower bleeding
      risks render allograft conduits preferable to synthetic conduits and,
      furthermore, because conduit insertion of any type in the neonate will eventually
      be outgrown and require replacement, we find this technique to be justifiable as
      a therapeutic option. In the short term, the technique results in excellent
      functional results and provides an alternative to synthetic conduits when an
      appropriate sized allograft is unavailable.

PMID- 8279925
TI  - Total anomalous pulmonary venous drainage in newborns with visceral heterotaxy.
AB  - Children with visceral heterotaxy often present with total anomalous pulmonary
      venous drainage (TAPVD) associated with univentricular congenital heart disease.
      We reviewed our experience with the primary surgical management of this lesion
      under these circumstances. Over a recent 10-year span, 38 patients within the
      first 3 days of life were admitted to our institution and underwent primary
      palliation. Twenty-one of them had TAPVD, 18 to a systemic vein. Twelve (67%) of
      these 18 were seen with obstruction of the anomalous connection and underwent
      emergency operation. In 7 patients, repair of TAPVD was combined with a systemic
      pulmonary artery shunt because of additional obstruction of the pulmonary blood
      supply, with two deaths. One patient had primary shunting and then repair of
      TAPVD. Four patients underwent repair of TAPVD alone. Two of them then showed
      signs of insufficient pulmonary blood flow, received a shunt in a second
      procedure, and subsequently died. Early mortality in the group with obstructed
      TAPVD was thus 4 (33%) of 12 patients. Statistical analysis of all 38 patients
      (univariate analysis, chi 2 testing) showed that neither the presence of TAPVD (p
      = 0.7) nor TAPVD repair alone (p = 0.8) or with shunting (p = 0.8) was a definite
      risk factor for early death. The performance of a shunt during the first
      operation, however, was associated with lower early mortality (p = 0.03). Total
      anomalous pulmonary venous drainage is a common finding in newborns with visceral
      heterotaxy. Its presence and its subsequent early repair (requiring
      cardiopulmonary bypass) do not increase the mortality risk. The need of a
      concomitant shunt in obstructed TAPVD can initially be underestimated.

PMID- 8279926
TI  - Liberalization of donor criteria in lung and heart-lung transplantation.
AB  - Since March 1986, we have performed 26 heart-lung transplantations, 42 single
      lung transplantations, 9 bilateral single-lung transplantations, and 1 double
      lung transplantation. The original lung donor requirements were as follows: age
      less than 40 years, no smoking history; no gram-negative rods or fungus on sputum
      Gram stain; arterial oxygen tension greater than 140 mm Hg on an inspired oxygen
      fraction of 0.40; no infiltrate or pneumothorax on the chest radiograph; and
      donor height within 15 cm (6 inches) of recipient height. As the number of
      potential recipients increased, so did the waiting time. To counter this delay,
      during the past year we have liberalized our donor criteria. We now accept lung
      donors up to age 60 years. Any kind of smoking history is acceptable unless there
      is chronic obstructive pulmonary disease or pulmonary fibrosis on the chest
      radiograph. Sputum must be free from fungus, but gram-negative rods are treated
      with appropriate antibiotics. The arterial oxygen tension on an inspired oxygen
      fraction of 0.40 should be greater than 100 mm Hg, and a small pulmonary
      infiltrate is not worrisome. This liberalization of the donor pool for lung and
      heart-lung transplantation has not adversely affected early outcome.

PMID- 8279927
TI  - Cerebral metabolic effects of sequential periods of hypothermic circulatory
      arrest.
AB  - During repair of congenital heart defects, extended periods of hypothermic
      circulatory arrest (CA) have been shown to cause short-term cerebral metabolic
      and flow abnormalities as well as long-term neuropsychologic dysfunction.
      Occasionally, a second period of CA is required during the same operative setting
      to revise a complicated repair. However, the metabolic effects of two consecutive
      periods of CA on the brain are unclear. In this study, we compared the recovery
      of cerebral metabolism after 60 minutes of CA with that after two sequential 30
      minute periods of CA separated by a brief period of rewarming (30'SEQ). Fifteen
      neonatal piglets (2 to 3 kg) were placed on cardiopulmonary bypass at 100 mL.kg-1
      x min-1 and cooled to 18 degrees C. Each animal then underwent either 60 minutes
      of uninterrupted cardiopulmonary bypass at 18 degrees C, 60 minutes of CA, or two
      30-minute periods of CA separated by a brief period of rewarming. After these
      experimental periods, animals were rewarmed to 37 degrees C and weaned from
      cardiopulmonary bypass. Data were obtained before cardiopulmonary bypass and
      after cardiopulmonary bypass at 37 degrees C and included measurements of
      cerebral blood flow by xenon 133 clearance, arterial and sagittal sinus blood
      gases, and cerebral metabolism (mL O2.100 g-1 x min-1). Our results demonstrated
      that acute recovery of cerebral metabolism was significantly impaired after 60
      minutes of CA and that recovery of cerebral metabolism after two sequential 30
      minute periods of CA was significantly better than after 60 minutes of continuous
      CA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279928
TI  - WHO Neuropsychiatric AIDS study, cross-sectional phase I. Study design and
      psychiatric findings.
AB  - BACKGROUND: Most available studies on the psychiatric, neuropsychological, and
      neurological complications of HIV-1 infection and AIDS have been conducted in
      Western countries, on samples of well-educated, mostly white, homosexual men.
      Concerns about generalizability of the results of those investigations prompted
      the WHO to implement the cross-cultural venture called WHO Neuropsychiatric AIDS
      study. METHODS: This project aims to assess the prevalence and natural history of
      HIV-1-associated psychiatric, neuropsychological, and neurological abnormalities
      in representative subject samples enrolled in the five geographic areas
      predominantly affected by the HIV-1 epidemic. Assessment is made by a data
      collection instrument including six modules. The intercenter and intracenter
      reliability in the use of each module has been formally evaluated. The study
      consists of a cross-sectional phase and a longitudinal follow-up. RESULTS: The
      cross-sectional phase was completed in five centers. This paper reports on the
      results of psychiatric assessment, which revealed a significantly higher
      prevalence of current mental disorders in symptomatic seropositive persons
      compared with seronegative controls among intravenous drug users in Bangkok and
      homosexuals/bisexuals in Sao Paulo. The mean global score on the Montgomery
      Asberg Depression Rating Scale was significantly higher in symptomatic
      seropositive individuals than in matched seronegative controls in all centers.
      CONCLUSIONS: These results suggest that the significance of the
      psychopathological complications of symptomatic HIV-1 infection may have been
      underestimated by previous studies conducted on self-selected samples of well
      educated, middle-class, mostly white, homosexual men.

PMID- 8279929
TI  - WHO Neuropsychiatric AIDS study, cross-sectional phase II. Neuropsychological and
      neurological findings.
AB  - BACKGROUND: The neuropsychological and neurological complications of HIV-1
      infection and AIDS were explored within the cross-sectional phase of the WHO
      Neuropsychiatric AIDS Study. Special attention was devoted to the controversial
      issue of the prevalence and clinical significance of subtle cognitive deficits in
      asymptomatic seropositive subjects. METHODS: A neuropsychological test battery
      validated for cross-cultural use, a structured interview for the diagnosis of
      dementia, a rating scale of functioning in daily living activities, and a
      neurological module were administered to representative samples of seropositive
      subjects and to matched seronegative controls living in the five geographic areas
      predominantly affected by the HIV-1 epidemic. Data are available for five
      centers. RESULTS: The prevalence of global neuropsychological impairment was
      significantly increased in asymptomatic seropositive subjects compared with
      controls in only two centers. A significant effect of education on
      neuropsychological performance was observed among asymptomatic seropositive
      individuals. In the two African centers, low-education, but not high-education,
      asymptomatic seropositive persons had an impaired performance. The frequency of
      impaired functioning in daily living activities and of neurologic abnormalities
      was higher in symptomatic, but not in asymptomatic, seropositive subjects
      compared with controls in all centers. CONCLUSIONS: These data suggest that the
      risk of subtle cognitive deficits may be increased in asymptomatic stages of HIV
      1 infection. However, these deficits are not associated with neurologic changes
      and do not seem to affect subjects' social functioning.

PMID- 8279930
TI  - Regional cerebral blood flow measured during symptom provocation in obsessive
      compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission
      tomography.
AB  - BACKGROUND: The study was designed to determine the mediating neuroanatomy of
      obsessive-compulsive disorder (OCD). METHODS: The short half-life tracer oxygen
      15-labeled carbon dioxide was used to allow for repeated positron emission
      tomographic determinations of regional cerebral blood flow on each of eight
      patients with OCD during a resting and a provoked (symptomatic) state. RESULTS:
      Individually tailored provocative stimuli were successful in provoking OCD
      symptoms, in comparison with paired innocuous stimuli, as measured by self-report
      on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a
      statistically significant increase in relative regional cerebral blood flow
      during the OCD symptomatic state vs the resting state in right caudate nucleus (P
      < .006), left anterior cingulate cortex (P < .045), and bilateral orbitofrontal
      cortex (P < .008); increases in the left thalamus approached but did not reach
      statistical significance (P = .07). CONCLUSIONS: These findings are consistent
      with results of previous functional neuroimaging studies and contemporary
      neurocircuitry models of OCD. The data further implicate orbitofrontal cortex,
      caudate nucleus, and anterior cingulate cortex in the pathophysiology of OCD and
      in mediating OCD symptoms.

PMID- 8279931
TI  - Violence in the severely mentally ill.

PMID- 8279932
TI  - Cingulotomy in a case of concomitant obsessive-compulsive disorder and Tourette's
      syndrome.

PMID- 8279933
TI  - Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United
      States. Results from the National Comorbidity Survey.
AB  - BACKGROUND: This study presents estimates of lifetime and 12-month prevalence of
      14 DSM-III-R psychiatric disorders from the National Comorbidity Survey, the
      first survey to administer a structured psychiatric interview to a national
      probability sample in the United States. METHODS: The DSM-III-R psychiatric
      disorders among persons aged 15 to 54 years in the noninstitutionalized civilian
      population of the United States were assessed with data collected by lay
      interviewers using a revised version of the Composite International Diagnostic
      Interview. RESULTS: Nearly 50% of respondents reported at least one lifetime
      disorder, and close to 30% reported at least one 12-month disorder. The most
      common disorders were major depressive episode, alcohol dependence, social
      phobia, and simple phobia. More than half of all lifetime disorders occurred in
      the 14% of the population who had a history of three or more comorbid disorders.
      These highly comorbid people also included the vast majority of people with
      severe disorders. Less than 40% of those with a lifetime disorder had ever
      received professional treatment, and less than 20% of those with a recent
      disorder had been in treatment during the past 12 months. Consistent with
      previous risk factor research, it was found that women had elevated rates of
      affective disorders and anxiety disorders, that men had elevated rates of
      substance use disorders and antisocial personality disorder, and that most
      disorders declined with age and with higher socioeconomic status. CONCLUSIONS:
      The prevalence of psychiatric disorders is greater than previously thought to be
      the case. Furthermore, this morbidity is more highly concentrated than previously
      recognized in roughly one sixth of the population who have a history of three or
      more comorbid disorders. This suggests that the causes and consequences of high
      comorbidity should be the focus of research attention. The majority of people
      with psychiatric disorders fail to obtain professional treatment. Even among
      people with a lifetime history of three or more comorbid disorders, the
      proportion who ever obtain specialty sector mental health treatment is less than
      50%. These results argue for the importance of more outreach and more research on
      barriers to professional help-seeking.

PMID- 8279934
TI  - The response of burn scars to intralesional verapamil. Report of five cases.
AB  - Postburn dermal scars can be aesthetically disfiguring and severely disabling.
      Existing medical and surgical strategies to prevent or to treat scars are all too
      often disappointing. More effective strategies are needed. It has been postulated
      that cell membrane calcium channel blockers could potentially trigger
      extracellular matrix degradation in dermal scars, resulting in scar volume
      reduction. To test this hypothesis, we studied the effects of intralesional
      verapamil hydrochloride therapy, 0.1 to 0.5 mmol/L, on scar volume and color in
      patients with burns. Our study chronicles five reports on arbitrarily selected
      clinical cases of hypertrophic burn scarring and the effect of therapy with
      intralesional verapamil. The cellular functions and processes explaining this
      effect are discussed. There were no significant side effects or complications
      from the verapamil therapy. It is now clear that regulation of fibroblast calcium
      metabolism is a safe and often effective strategy to treat hypertrophic scars. To
      our knowledge, this is the first clinical report of control of burn scar with
      calcium channel blockers.

PMID- 8279935
TI  - Surgery in Australia.
AB  - More than 4000 surgeons in Australia provide services to 17.6 million people
      living in the world's driest continent, with a land mass comparable to that of
      the United States. The problem of distance has been overcome in large part for
      the 17% of the population who live in remote areas by modern communication
      systems and by the Flying Doctor and Flying Surgeon services. For the remaining
      population, largely clustered on the fertile eastern seaboard, surgical services
      rival the best in the world, and surgical training, under the control of The
      Royal Australasian College of Surgeons, has set an example for which Australia
      can be justifiably proud.

PMID- 8279936
TI  - History repeats itself. Connections and causality in the study of surgical
      infections.

PMID- 8279937
TI  - Assessment of hepatitis B virus immunization status among North American
      surgeons.
AB  - OBJECTIVE: We hypothesized that many surgeons have not been vaccinated against
      hepatitis B virus (HBV), despite the existence of effective recombinant vaccines.
      Prevalence of HBV vaccination among surgeons, attitudes of those not vaccinated,
      estimated HBV infection rates, and respondents' knowledge of the epidemiology of
      HBV exposure were determined. DESIGN: Survey conducted by mail just before
      implementation of mandatory HBV vaccination for health care workers. SETTING:
      Private and academic general surgical, trauma and transplantation practices.
      PARTICIPANTS: Two thousand one hundred twenty-five surgeons received the survey.
      Response rates are as follows: in the Surgical Infection Society, 196 (50%) of
      393 surgeons; in the American Association for the Surgery of Trauma, 223 (52%) of
      433 surgeons; in the American Society of Transplant Surgeons, 194 (44%) of 438
      surgeons; and among the Fellows of the American College of Surgeons, 403 (47%) of
      861 surgeons. MAIN OUTCOME MEASURES: Prevalence of HBV exposure and active
      immunization by specialty and society. RESULTS: Prevalence of HBV exposure was
      19.6%, was higher among trauma and transplantation surgeons compared with general
      surgeons (P < .0001), and increased significantly with age in all groups (P <
      .05). Despite greater exposure, probable immunity was lower at an older age
      because young surgeons (age, < 46 years) are more likely to be vaccines (P <
      .05). Most surgeons (55%) were vaccinated more than 5 years ago; many recipients
      of recombinant vaccines (26%) received an inadequate amount of vaccine or were
      improperly vaccinated. Knowledge of the epidemiology was uniformly poor, with
      rates of correct responses to the three questions below 50%. CONCLUSIONS:
      Vaccination does not equal immunity. Between 38% and 50% of practicing surgeons
      may not have adequate immunity to HBV.

PMID- 8279938
TI  - Steroids, APACHE II score, and the outcome of abdominal infection.
AB  - OBJECTIVE: To compare the outcome of abdominal infection in patients with or
      without previous systemic glucocorticoid therapy and to determine the effect of
      steroid administration on the relationship between APACHE II (Acute Physiology
      and Chronic Health Evaluation) scores and mortality. HYPOTHESIS: Steroid therapy
      leads to greater mortality and relatively lower APACHE II scores. DESIGN:
      Prospective cohort study. SETTING: University hospital. PATIENTS: Two hundred
      ninety-seven consecutive adult patients with abdominal infection treated by
      surgical or percutaneous drainage. Treatment was at the clinician's discretion.
      Seventy-one patients received systemic steroid therapy. OUTCOME MEASURES: APACHE
      II score, clinical course, and death in hospital; relationship between APACHE II
      score and mortality in the steroid and no steroid groups. RESULTS: Thirty-three
      patients receiving steroid therapy (46%) died vs 55 (24%) of 226 patients not
      receiving steroid therapy. The APACHE II score (P < .0001) and steroid
      administration (P = .04) were each independently associated with death. Steroid
      treated patients had the same probability of dying as "nonsteroid" patients with
      an APACHE II score a mean of 3.7 points higher (95% confidence limits, 0.03 and
      7.7). The confidence that 2, 3, or 4 extra APACHE II points is the appropriate
      correction for steroid-treated patients is 80%, 60%, or 40%, respectively.
      CONCLUSIONS: Patients receiving steroid therapy appear to be at higher risk of
      dying of abdominal infection than predicted by APACHE II scores. The number of
      patients receiving cancer chemotherapy was too small to determine whether this
      was an additional risk factor. In the design of clinical trials stratified by
      APACHE II scores, steroid-treated patients should either be excluded or assigned
      two extra APACHE II points.

PMID- 8279939
TI  - Early predictors of postinjury multiple organ failure.
AB  - OBJECTIVE: To find a predictive model for postinjury multiple organ failure
      (MOF). DESIGN: A 3-year cohort study ending December 1992 (first year:
      retrospective; last 2 years: prospective). SETTING: Denver General Hospital
      (Colo) is a regional level I trauma center. PATIENTS: Consecutive trauma patients
      with an Injury Severity Score (ISS) greater than 15, with an age greater than 16
      years, and who survived longer than 24 hours. Stepwise logistic regression
      analysis was performed in all patients (n = 394), in the subgroup of patients
      with 0 to 12 hours, plus 12 to 24 hours base deficit (BD) results (n = 220), and
      in a second subgroup of patients with BD plus lactate results at 0 to 12 hours
      and 12 to 24 hours (n = 106). MAIN OUTCOME: Postinjury MOF. RESULTS: The
      following variables were identified as independent predictors of MOF in the
      analysis of all patients: age more than 55 years, ISS greater than or equal to
      25, and more than 6 U of red blood cells in the first 12 hours after admission (U
      RBC/12 hours). In the subgroup with BD results, the same analysis identified age
      greater than 55 years, greater than 6 U RBC/12 hours, and BD greater than 8 mEq/L
      (0 to 12 hours), while in the last subgroup analysis including BD and lactate
      results, greater than 6 U RBC/12 hours, BD greater than 8 mEq/L (0 to 12 hours),
      and lactate greater than 2.5 mmol/L (12 to 24 hours) were independently
      associated with MOF. CONCLUSIONS: Age greater than 55 years, ISS greater than or
      equal to 25, and greater than 6 U RBC/12 hours are early independent predictors
      of MOF. Subgroup analyses indicate that BD and lactate levels may add substantial
      predictive value. Moreover, these results emphasize the predominant role of the
      initial insult in the pathogenesis of postinjury MOF.

PMID- 8279940
TI  - Oxygen transport-dependent splanchnic metabolism in the sepsis syndrome.
AB  - OBJECTIVE: Total body oxygen consumption (VO2) may be pathologically oxygen
      delivery (DO2)-dependent in critically ill patients exhibiting the sepsis
      syndrome. This observation has been used to infer the presence of occult tissue
      or organ ischemia that potentially can be eradicated by augmenting DO2. We
      examined this hypothesis by determining the VO2-DO2 relationship and lactate
      metabolism in the splanchnic region. DESIGN: Before and after intervention trial.
      SETTING: University-affiliated Veterans Affairs Medical Center, Allen Park, Mich.
      PATIENTS: Eighteen surgical patients exhibiting the sepsis syndrome.
      INTERVENTION: Systemic and splanchnic oxygen exchange and lactate uptake
      measurements before and after augmentation of DO2 with blood transfusion. MAIN
      OUTCOME MEASURES: Changes in oxygen exchange and lactate metabolism. RESULTS: The
      splanchnic VO2 index rose 9% in association with a 26% regional DO2 index
      increase indicating an oxygen transport dependency (P < .05). Splanchnic O2
      extraction (0.47 +/- 0.04) was significantly greater than the mean systemic level
      (0.31 +/- 0.02) and showed a greater decline following DO2 index augmentation
      (0.41 +/- 0.04 vs 0.28 +/- 0.03, respectively). However, splanchnic lactate
      uptake was not changed significantly in response to the increased DO2 index.
      CONCLUSIONS: Although splanchnic oxygen transport dependency and elevated
      extraction ratios suggest the presence of regional ischemia that should be
      relieved with an increased DO2 index, the observed changes in lactate uptake do
      not support this conclusion. The significance of the VO2-DO2 relationship, its
      role in the pathophysiology of the sepsis syndrome, and its place in the clinical
      care of the septic surgical patient are in doubt.

PMID- 8279941
TI  - The primary site of bacterial translocation.
AB  - OBJECTIVE: To establish the primary anatomic site of bacterial translocation in
      the intestinal tract. DESIGN: Prospective randomized experimental trials.
      SETTING: Laboratory. MATERIALS: Hartley guinea pigs. INTERVENTIONS: In guinea
      pigs, 10-cm closed loops of upper jejunum, distal ileum, or proximal colon were
      created. The animals then received intraluminal injections of Escherichia coli
      labeled with radioactive carbon (14C) before a 50% full-thickness burn was
      inflicted. Four hours after the burn injury, the animals were killed, and the
      intestinal loops, mesenteric lymph nodes, spleen, liver, and lung were harvested.
      Intestinal loops were irrigated and then treated with
      ethylenedinitroilotetraacetic acid to separate the enterocytes and colonocytes
      from the lamina propria. Radionuclide counts were determined in the effluents,
      the enterocytes (or colonocytes), lamina propria, and other organs. Colony
      forming units of E coli were also determined in mesenteric lymph nodes, spleen,
      liver, and lung. MEASUREMENTS AND MAIN RESULTS: No significant differences were
      noted in the radionuclide counts in the lamina propria and epithelial cell
      fraction related to the type of loop. In addition, no significant differences
      were noted in the radionuclide counts in the mesenteric lymph nodes, liver,
      spleen, and lung related to the type of loop, but more viable bacteria were
      recovered when bacteria were injected into the jejunal loop. CONCLUSIONS:
      Translocation of bacteria occurred with similar intensity throughout the gut, but
      more bacteria were killed in the process of translocation across the lower part
      of the intestinal tract.

PMID- 8279942
TI  - Effect of recombinant human insulin-like growth factor I and early total
      parenteral nutrition on immune depression following severe head injury.
AB  - OBJECTIVE: To determine the effects of insulin-like growth factor I (IGF-I) and
      aggressive nutrition on CD4/CD8 ratios following head injury. DESIGN: Randomized
      controlled trial. SETTING: An urban level 1 trauma center. PARTICIPANTS: Head
      injured patients with a Glasgow Coma Scale score of 4 to 10 within 6 hours of
      hospital admission requiring no major extracranial surgery with the exception of
      isolated lower-extremity fracture fixation. Fourteen patients were recruited and
      11 completed the study. INTERVENTIONS: Patients were randomized to a continuous
      infusion of saline or 0.01 mg/kg per hour of recombinant human (rh) IGF-I. Both
      groups received parenteral nutrition and rapidly advanced to a total protein
      intake of 2 g/kg per day and a maximum nonprotein calorie intake of 40 kcal/kg
      per day. The nonprotein prescription was 1.25 times the metabolic energy
      expenditure determined by metabolic cart not to exceed a nonprotein calorie
      intake of 40/kcal. MAIN OUTCOME MEASURES: The CD4/CD8 ratios and serum IGF-I
      levels on days 1, 7, and 14. RESULTS: Administration of early aggressive
      nutrition eliminated the depressed CD4/CD8 ratio usually seen after head injury;
      administration of IGF-I increased the CD4/CD8 ratio while IGF-I levels were
      elevated. CONCLUSIONS: Infusion of rhIGF-I and aggressive early intravenous
      nutrition affects the immunologic response of patients with severe head injury.

PMID- 8279944
TI  - Delayed tumor necrosis factor alpha blockade attenuates pulmonary dysfunction and
      metabolic acidosis associated with experimental gram-negative sepsis.
AB  - OBJECTIVE: To ascertain the effect of delayed tumor necrosis factor alpha (TNF
      alpha) on the evolution of systemic and pulmonary injury after the onset of
      sepsis. DESIGN: Prospective controlled trial. INTERVENTION: Anesthetized swine
      were made septic with a 1-hour infusion of live Pseudomonas aeruginosa, following
      which a treatment group received an infusion of anti-TNF-alpha monoclonal
      antibody (5 mg/kg). Control animals received 0.9% saline. RESULTS: Delayed anti
      TNF-alpha treatment had no effect on septic pulmonary hypertension or decline in
      cardiac output. Late recovery in systemic arterial hypotension was associated
      with a reversal of arterial acidosis (P < .05 by t test and analysis of variance
      with Tukey's Studentized Range Test) compared with unprotected septic animals.
      Septic animals had a significant increase in mean (+/- SEM) plasma lactate levels
      at 5 hours compared with baseline values (3.8 +/- 0.7 vs 2 +/- 0.4, P < .05), but
      remained unchanged from baseline following anti-TNF-alpha treatment (1.5 +/- 0.1
      vs 1.6 +/- 0.2, not significant). Characteristic septic neutropenia was
      dramatically reversed by anti-TNF-alpha treatment and was associated with
      downregulation (P < .05 by t test and analysis of variance) of polymorphonuclear
      neutrophil (PMN) leukocyte CD18 adhesion receptors and reduction (P < .05 by t
      test and analysis of variance) in lung PMN sequestration measured by
      myeloperoxidase activity. The mean (+/- SEM) decrease in bronchoalveolar lavage
      protein indicated an attenuated permeability injury in anti-TNF-alpha animals
      (septic animals at 5 hours compared with baseline value, 1044 +/- 270 vs 149 +/-
      28 micrograms/mL; control animals at 5 hours compared with baseline value, 217 +/
      83 vs 129 +/- 19 micrograms/mL; P < .05 by t test and analysis of variance).
      CONCLUSIONS: These data show that delayed anti-TNF-alpha treatment reversed
      metabolic acidosis associated with sepsis. Furthermore, anti-TNF-alpha treatment
      reversed septic neutropenia, reduced PMN sequestration, and was associated with
      attenuated lung injury in a model of fulminant sepsis. This supports evidence of
      PMN-mediated tissue injury in sepsis and suggests mechanisms for potential
      therapeutic benefit of anti-TNF-alpha treatment in clinical practice.

PMID- 8279943
TI  - The metabolic effects of platelet-activating factor antagonism in endotoxemic
      man.
AB  - OBJECTIVE: To determine if the inflammatory phospholipid platelet-activating
      factor (PAF) participated in the symptomatologic, metabolic, and
      counterregulatory hormonal responses of human endotoxemia. DESIGN: In a double
      blind, placebo-controlled study, five subjects received 10 mg of the PAF
      antagonist Ro 24-4736 orally, while five control subjects received a placebo.
      Eighteen hours later, all subjects were administered 4 ng/kg of endotoxin
      (lipopolysaccharide) intravenously. SETTING: The Clinical Research Center of The
      New York Hospital-Cornell Medical Center. PARTICIPANTS: Healthy male volunteers.
      MAIN OUTCOME MEASURES: Repeated measurements of vital signs, symptoms, cytokine
      and hormone levels, resting energy expenditure, platelet aggregation, and
      bleeding times were performed during a 24-hour period. RESULTS: Subjects who were
      pretreated with the PAF antagonist experienced fewer symptoms, including rigors
      at 1 hour (P < .05) and myalgias at 1 through 4 hours (P < .05) after
      administration of lipopolysaccharide. This was in concert with a diminished peak
      cortisol level (668 +/- 107 vs 959 +/- 159 nmol/L in controls; P < .05),
      epinephrine secretion (1057 +/- 165 vs 2029 +/- 431 nmol/L in controls; P < .05),
      and almost complete inhibition of PAF-induced platelet aggregation ex vivo.
      CONCLUSIONS: These findings in the face of unaltered circulating cytokines tumor
      necrosis factor alpha, interleukin 1 beta, and interleukin 6, as well as the
      tumor necrosis factor receptor-I s, suggest that PAF may influence some endotoxin
      induced, counterregulatory hormonal responses and symptoms through cytokine
      independent mechanisms. This study further supports the role of PAF antagonists
      as an adjunct to cytokine blockade in the treatment of gram-negative sepsis.

PMID- 8279945
TI  - Enhanced release of elastase is not concomitant with increased secretion of
      granulocyte-activating cytokines in whole blood from patients with sepsis.
AB  - BACKGROUND: The proteolytic enzyme elastase released by granulocytes
      (polymorphonuclear leukocytes [PMN]) in high concentrations during sepsis causes
      degradation of essential plasma proteins, endothelial damage, and tissue edema.
      This may result in organ dysfunction and organ failure during sepsis, since
      increased elastase plasma levels correlate with the mortality rate of patients
      with sepsis. In vitro studies demonstrated a regulatory role of inflammatory
      cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin 1 beta [IL-1
      beta], IL-8]) upregulating protease release by PMN. In this light, the
      interactions between cytokine release by macrophages and altered elastase
      secretion during sepsis remain to be determined. METHODS: An ex vivo model
      consisting of lipopolysaccharide stimulation of human whole blood as a relevant
      physiological milieu was used. Heparinized blood was obtained from 20 patients
      with sepsis syndrome (APACHE II [Acute Physiology and Chronic Health Evaluation
      II] score 28.5 +/- 1.2 points [mean +/- SD]) on days 0 through 3, 5, 7, and 10
      after sepsis diagnosis and from 20 control patients without infection. Blood was
      incubated with lipopolysaccharide (1 mg/L) for 8 hours. Plasma levels of
      elastase, TNF-alpha, IL-1 beta, and IL-8 were determined using enzyme-linked
      immunosorbent assay or bioassay (TNF-alpha), respectively. RESULTS: Elastase
      plasma levels in whole blood from patients with sepsis were increased up to 188%
      (P < .01) above normal, while the release of TNF-alpha (-87%), IL-1 beta (-91%),
      and IL-8 (-51%) was markedly (P < .01) decreased compared with control patients.
      Neutralization of TNF-alpha or IL-1 beta did not attenuate the increased release
      of elastase. CONCLUSIONS: These data indicate an increased release of elastase by
      PMN despite a reduced secretion of PMN-activating cytokines. Although priming
      effects of TNF-alpha, IL-1 beta, and IL-8 on protease secretion in vivo cannot be
      excluded completely, other mediators or mechanisms may be involved in the
      upregulation of detrimental protease release during sepsis.

PMID- 8279946
TI  - Exudative neutrophils. Modulation of microbicidal function in the inflammatory
      microenvironment.
AB  - OBJECTIVE: To determine whether the inflammatory microenvironment primes
      neutrophils for increased microbicidal activity. DESIGN: In vitro studies of host
      defense were performed on surgical patients. SETTING: A tertiary care, university
      hospital. PATIENTS: A volunteer sample of hospitalized preoperative, noninfected
      surgical patients. INTERVENTION: Exudative neutrophils were collected from skin
      blister chambers and functionally compared with circulating neutrophils. METHODS:
      Flow cytometry was used to evaluate directly neutrophil microbicidal activity
      (using fluoresceinated Candida albicans), formyl-methionyl-leucyl-phenylalanine
      (fMLP)-induced superoxide production (using 123 dihydrorhodamine), and surface
      expression of CD11b, CD16, and the fMLP receptor. In vitro tumor necrosis factor
      alpha was used to determine the possibility and extent of further priming in both
      circulating and exudative neutrophils. RESULTS: Exudative polymorphonuclear
      neutrophils have enhanced microbicidal activity, superoxide production, and
      expression of CD11b, CD16, and the fMLP receptor. Exogenous tumor necrosis factor
      was able to prime circulating neutrophils but did not further augment superoxide
      production in exudative neutrophils. CONCLUSION: The microbicidal activity of
      neutrophils is enhanced after exudation and is associated with neutrophil
      priming. The inability of exogenous tumor necrosis factor to further augment
      superoxide production after exudation suggests that this priming has been
      maximized.

PMID- 8279947
TI  - Hepatitis B virus proteins expressed by recombinant vaccinia viruses: influence
      of preS2 sequence on expression surface and nucleocapsid proteins in human
      diploid cells.
AB  - Fifteen vaccinia virus (VV) recombinants derived from VV strains Praha, LIVP and
      DD (i.e. Dryvax Wyeth vaccine-derived) and expressing genes for S, preS2-S or c
      antigens of hepatitis B virus (HBV) were tested in monkey CV-1 cells and human
      diploid LEP cells. The production of infectious virus was found to be alike in
      all the recombinants and parental viruses as well. However, several recombinants
      produced markedly lesser amounts of S and preS2 antigens in LEP cells than in CV
      1 cells. This reduction was independent of the parental virus used. There was,
      however, a relationship between the production of preS2 in CV-1 cells and the
      production of S and preS2 antigens in LEP cells; in general, recombinants
      efficiently inducing preS2 antigen formation in CV-1 cells produced markedly
      reduced amounts of S and preS2 antigens in LEP cells. Reduction of HBV antigen
      production in LEP cells was not apparent in recombinants expressing only S or c
      antigens of HBV, and the production of c antigen by double recombinants was not
      influenced by simultaneous expression of preS2 and S. The various recombinants
      also differed in the ratio of S:preS2 antigen formation. This difference seemed
      to be associated with the length of the untranslated leader sequence preceding
      preS2 but not with the parental virus or cell type used. The titers of antibodies
      against S and preS2 antigens induced in mice immunized with different
      recombinants differed markedly. The differences in the ratio of S:preS2 antigen
      production in vitro were not reflected in vivo by S:preS2 antibody ratio.

PMID- 8279948
TI  - Temperature-sensitive steps in the transport of Semliki Forest virus envelope
      proteins in mosquito C6/36 cells.
AB  - We have analysed the temperature dependence of the transport of Semliki Forest
      virus (SFV) envelope proteins in mosquito cells, the natural host cells of
      alphaviruses. These cells are cultivated at a lower temperature (28 degrees C)
      and have a different lipid composition as compared to mammalian cells. When the
      incubation temperature was reduced at early times after infection, the onset of
      virus shedding was delayed and the maximal titers decreased correspondingly to
      the temperature. No virus was shed at 12 degrees C. No evidence was observed for
      a block of virus release due to a shift of the sites of virus maturation. When
      the incubation temperature was reduced at later times after infection a critical
      temperature of 12 degrees C was again observed. At this temperature no transport
      of viral proteins took place, p62 remained uncleaved, the glycan processing of E1
      did not occur and the envelope proteins accumulated in a pre-Golgi compartment.
      We suggest a mathematical formula which allows the extrapolation of transport
      data to the temperature at which intracellular protein transport becomes blocked.

PMID- 8279949
TI  - Genetic analysis of echovirus 11 variability in adsorption to human erythrocytes.
AB  - The frequency of nonhemagglutinating (h-) mutants was determined in
      hemagglutinating (HA) clones of echovirus 11. The HA clones were derived from the
      prototype strain Gregory and a clinical isolate of echovirus 11. The h- mutants
      were found at a constant frequency of 3.0 x 10(-5) (mean value) in the HA clones
      derived from both strains. Since the conditions of the population equilibrium of
      HA clones and neutrality of the mutation were satisfied, it was proposed that the
      observed frequency of h- mutants occurred as a result of a point mutation. The
      frequency of h+ revertants at the second passage of h- mutant clone was 9.1 x 10(
      5). Hence the frequency of reversion suggests that the number of potential sites
      of back mutation was restricted.

PMID- 8279950
TI  - Characterization of the transforming domain of a feline sarcoma virus encoding a
      fgr-related tyrosine kinase.
AB  - We investigated the transforming domain of a recently isolated feline sarcoma
      virus (TP1-FeSV) which encodes a fgr-related tyrosine kinase expressed as a gag
      fgr fusion protein. The gag portion was removed and replication-competent
      expression vectors (RCAS) with inserted v-fgr sequences were established. Chicken
      embryo fibroblasts (CEF) were transfected and monitored for replication,
      integration and transcription of the proviral constructs. We demonstrated that
      transfected cells display morphological changes and are able to form colonies in
      soft-agar. This suggests that the gag portion of the fusion protein from TP1-FeSV
      is not necessary for the transformation of fibroblasts.

PMID- 8279951
TI  - Mutual interactions between HIV-1 and cytokines in adherent cells during acute
      infection.
AB  - The production of cytokines by HIV-infected cells from adherent tissues as well
      as their effects on HIV replication in the same cells were investigated. CD4
      transfected HeLa-T4-6c epithelial cells, CD4-positive normal lung fibroblasts and
      CD4-negative RD rhabdomyosarcoma cells were infected with HIV-1. All cultures
      were permissive for virus replication, which was completed within 48-72 h by Hela
      T4-6c and RD cells and 2-3 weeks in normal fibroblasts. During the course of HIV
      replication, a series of cytokines (particularly IL-6 and TNF alpha) was produced
      and released in parallel to the peak of virus growth, in amounts varying with the
      cell system studied. Treatment of cultures with recombinant cytokines given at
      concentrations in the range of those induced by HIV-1 indicated that IL-6 and TNF
      alpha caused an increase of: i) CD4 expression, ii) HIV absorption to uninfected
      cells, and iii) release of infectious virions by infected cells. The fact that
      HIV-1 absorption and spread can be mediated by HIV-induced cytokines may be
      relevant in the pathogenesis of the in vivo disease, as it may constitute a
      possible self-enhancing model of HIV infection also in the solid tissues.

PMID- 8279953
TI  - Origin and evolutionary pathways of the H1 hemagglutinin gene of avian, swine and
      human influenza viruses: cocirculation of two distinct lineages of swine virus.
AB  - The nucleotide sequences of the HA1 domain of the H1 hemagglutinin genes of
      A/duck/Hong Kong/36/76, A/duck/Hong Kong/196/77, A/sw/North Ireland/38,
      A/sw/Cambridge/39 and A/Yamagata/120/86 viruses were determined, and their
      evolutionary relationships were compared with those of previously sequenced
      hemagglutinin (H1) genes from avian, swine and human influenza viruses. A
      pairwise comparison of the nucleotide sequences revealed that the genes can be
      segregated into three groups, the avian, swine and human virus groups. With the
      exception of two swine strains isolated in the 1930s, a high degree of nucleotide
      sequence homology exists within the group. Two phylogenetic trees constructed
      from the substitutions at the synonymous site and the third codon position showed
      that the H1 hemagglutinin genes can be divided into three host-specific lineages.
      Examination of 21 hemagglutinin genes from the human and swine viruses revealed
      that two distinct lineages are present in the swine population. The swine
      strains, sw/North Ireland/38 and sw/Cambridge/39, are clearly on the human
      lineage, suggesting that they originate from a human A/WSN/33-like variant.
      However, the classic swine strain, sw/Iowa/15/30, and the contemporary human
      viruses are not direct descendants of the 1918 human pandemic strain, but did
      diverge from a common ancestral virus around 1905. Furthermore, previous to this
      the above mammalian viruses diverged from the lineage containing the avian
      viruses at about 1880.

PMID- 8279952
TI  - Inter- and intra-strain genomic variation in equine herpesvirus type 1 isolates.
AB  - Restriction enzyme digests of DNA from 22 unselected isolates of EHV-1 were
      analysed by hybridization with cloned DNA fragments covering the genome. In
      addition to a small amount of inter-strain variation, heterogeneity within
      strains was observed, caused by loss of specific restriction endonuclease sites
      in the DNA of a proportion of the virus particles of any one stock. Fifteen
      strains demonstrated the same intra-strain variation involving loss of the BamHI
      L-M site which was shown to lie within coding sequence for the large subunit of
      ribonucleotide reductase. This particular mutation may therefore be selected for
      by passage in RK13 cells.

PMID- 8279954
TI  - Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing
      antibodies.
AB  - In combination with HIV gp120 V3-loop antibody, two carbohydrate specific
      neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on
      HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding
      (1B1) both displayed antagonism.

PMID- 8279955
TI  - Detection by immunogold labelling of P75 readthrough protein near an extremity of
      beet necrotic yellow vein virus particles.
AB  - RNA 2 of beet necrotic yellow vein virus carries the cistron for the 21 kd coat
      protein at its 5'-extremity. During translation, the coat protein cistron
      termination codon is suppressed about 10% of the time so that translation
      continues into the adjacent open reading frame to produce a 75 kd species, known
      as P75, which contains the coat protein sequence at its N-terminus.
      Immunoblotting experiments with a P75-specific antiserum showed that P75 is
      present in only trace amounts in purified virus preparations. Electron
      microscopic visualization of immunogold-labelled virions in crude tissue extracts
      has provided evidence for an association between P75 and at least a fraction of
      the BNYVV particles, with P75 being predominantly located near one end of the rod
      shaped virions. This finding is discussed in the context of the current model for
      the role of P75 in virus assembly and vector transmission.

PMID- 8279956
TI  - Assembly of enveloped respiratory syncytial virus particles within the cytoplasm
      of infected Vero cells.
AB  - Electron microscopic examination of syncytia induced by a bovine respiratory
      syncytial virus strain in Vero cell cultures revealed the presence in the
      cytoplasm of assembled enveloped virus particles within inclusions of variable
      sizes. Moreover, budding virus particles were shown occasionally in the
      intracytoplasmic vesicles. These particles were filamentous in form, about 80-120
      nm in diameter, variable in length, containing 12 nm diameter nucleocapsids, and
      looked like the extracellular particles budding at the plasma membranes. This is
      the first report on assembly of intracellular virus particles in cells infected
      by a member of the family Paramyxoviridae. Vero cell-dependent variations appear
      to be the factor leading to the defect in the late virus replication cycle.

PMID- 8279957
TI  - Modifications to the rules for virus nomenclature.

PMID- 8279958
TI  - Pestivirus diversity.

PMID- 8279959
TI  - A rapid method for detection and identification of flaviviruses by polymerase
      chain reaction and nucleic acid hybridization.
AB  - A polymerase chain reaction (PCR) technique was developed and evaluated for the
      detection of flaviviruses. A set of sense and antisense oligomeric DNA primers
      were constructed from nucleotide sequences of the conserved region of the genome
      of several different flaviviruses. Virus specific complementary DNA (cDNA) was
      prepared by reverse transcription of total RNA extracted from infected cell
      cultures. Amplified cDNA was identified by nucleic acid hybridization with
      specific oligomeric internal probes. Various conditions, such as number of cycles
      and annealing temperature were examined to optimize the detection of viral RNAs
      from infected cell cultures. Slot blot hybridization with a radioactive probe was
      used to evaluate the sensitivity of PCR amplification. The PCR amplified RNA
      sequences of dengue 2 (DEN-2), West Nile (WN), St. Louis encephalitis (SLE) and
      Kunjin (KUN) virus and detected 0.1 to 1 pg of viral RNA. Japanese encephalitis
      (JE), Yellow Fever virus (YF), DEN-1, 3, and 4 viruses were not amplified. The
      more frequent occurrence of mismatches in the 3' primer binding site may explain
      the failure to amplify cDNA of these viruses.

PMID- 8279960
TI  - Development of specific antibody patterns and clinical symptoms following Ockelbo
      virus infection.
AB  - Sixteen patients with symptoms typical for Ockelbo disease (rash, arthralgia,
      fever) were enrolled in a 2 1/2 year study, during which clinical symptoms were
      recorded and ELISA was employed to study specific IgM, IgG and IgG subclass
      development. Initially, all patients presented with rash and arthralgia, and five
      patients still suffered from joint symptoms at the end of the study period.
      Ockelbo virus specific IgM was detected during the first week post onset in 6
      patients and in 15 patients by day 14. One patient failed to develop specific IgM
      and was later diagnosed with a human parvovirus B19 infection. All patients were
      IgM-negative 2 1/2 years post onset. Seroconversions or significant titer rises
      for specific total IgG were seen in 15 patients. IgG titers generally peaked
      within one year but in two patients maximum titers were seen 2 1/2 years post
      onset. Development of IgG1 followed that of total IgG, while IgG3, after an
      initial increase in all Ockelbo disease patients, remained at peak levels for one
      year in four patients, three of whom still had detectable IgG3 at the end of the
      study period. Ockelbo virus specific IgG2 or IgG4 was not detected in any of the
      patients.

PMID- 8279961
TI  - Herpes simplex virus type 1 (HSV-1) UL56 gene is involved in viral
      intraperitoneal pathogenicity to immunocompetent mice.
AB  - A comparison of the pathogenicity in mice of the recombinant herpes simplex virus
      type 1 (HSV-1) strain HSV-1-M-LacZ, in which the UL56 gene has been deleted, was
      made with its parental strain F, following infection in different mouse strains.
      The polymerase chain reaction (PCR) technique was used to study the migration of
      virus DNA in the mouse model. Tissues from adult mice infected intraperitoneally
      (IP) with one of three HSV-1 strains (F, HFEM or HSV-1-LacZ) were examined for
      the presence of viral DNA. DNA of the pathogenic strain F was detected in the
      adrenal glands, spinal cord, brain, liver and pancreas. DNA of HSV-1-M-LacZ was
      detected in the same tissues. However, DNA of the apathogenic strain HFEM was
      detected transiently (on days 2 and 3 p.i., but not days 1, 5 or 7), only in the
      adrenal glands and no viral DNA was detected in any of the other tissues. HSV-1
      pathogenic strains injected intraperitoneally into newborn mice (7 days old)
      killed most of the mice. In the surviving mice viral DNA of the three virus
      strains was found in peritoneal exudate cells (PEC), adrenal glands, spinal cord,
      liver and spleen. It was found that HSV-1-M-LacZ, which lacks the UL56 gene,
      resembled in pathogenicity to the newborn mice the pathogenic HSV-1 strains F and
      KOS. The PCR technique was used to trace viral DNA in tissues of the mice which
      survived HSV-1 infection at 7 weeks of age. Only HSV-1 (KOS) DNA was detected in
      the pancreas. The brains of these mice did not contain viral DNA. It is suggested
      that HSV-1 DNA may reside in surviving HSV-1- infected newborn mice in a "latent"
      state in nonneural tissues.

PMID- 8279962
TI  - A new natural reservoir of hantavirus: isolation of hantaviruses from lung
      tissues of bats.
AB  - Two species of bats were confirmed as new natural reservoirs of hantavirus.
      Antibodies to Hantaan virus were detected in 3.40% (23 of 677) of bats captured
      from 1989 to 1992 in Korea by the IFA technique. Areal distribution of
      immunofluorescent antibody were different, and seropositive rates were much high
      in sera of bats captured in summer (3.82%) and winter (5.82%). Viral antigens
      were observed in the lungs (3 of 16) and kidney (1 of 7). Two hantaviruses were
      isolated from lung tissues of E. serotinus and R. ferrum-equinum through a cell
      culture system, designated CUMC-92B8 and -92B48, respectively. Using Rous
      associated virus-2 reverse transcriptase-directed PCR and 2 oligonucleotide
      primer pairs, genomic sequences of the isolates were amplified. Amplified
      products of the isolates and reactivities to monoclonal antibodies very closely
      resembled those of Hantaan virus. These data suggest that the serotype of the
      isolates is closely related to Hantaan virus, and bats serve as reservoirs of
      hantavirus.

PMID- 8279964
TI  - [Food allergy].

PMID- 8279963
TI  - Gastrointestinal invasion by herpes simplex virus type 1 inoculated cutaneously
      into the immunosuppressed mice.
AB  - The pathogenesis of infection in mice with herpes simplex virus type 1 (HSV-1)
      strain 7401H was studied. Mice immunosuppressed by intraperitoneal injection of
      cyclophosphamide were inoculated cutaneously into the flank with the virus and
      developed severe zosteriform skin lesions. All of them died within 2 weeks after
      the infection, while most of the normal mice survived the viral infection with
      healing of the lesions. In the gastrointestinal tract of the immunosuppressed
      mice, macroscopic abnormalities were frequently observed, and infectious viruses
      were detected on days 7 to 9. The viruses were also detectable in the dorsal root
      ganglia and the spinal cord of thoracolumbar area on days 5 to 7, and in the
      celiac plexus on day 7. However, no viruses were detected in the blood.
      Immunohistological examination of the gastrointestinal tract revealed that the
      viral antigens were localized in Auerbach's myenteric plexus. These results
      suggest that HSV-1 inoculated into the flank skin invaded the gastrointestinal
      tract via the nervous system, which gastrointestinal involvement might possibly
      have caused the death of the mice.

PMID- 8279965
TI  - [Circulating immune complexes and anti-mite specific IgG antibody in status
      asthmatics--effects of methylprednisolone and analysis of an anti-complementary
      factor].
AB  - Serial changes of circulating immune complexes and anti-mite specific IgG
      antibody in the peripheral blood were measured eight times in six status
      asthmatics treated with high doses of methylprednisolone (MPS). Circulating
      immune complexes decreased to normal levels three hours after MPS administration.
      By contrast, anti-mite specific IgG antibody increased to beyond the normal range
      14 days after MPS administration. Serum levels of IgE and allergen specific IgG4
      antibody did not show any significant changes. In vitro experiments, circulating
      immune complexes in the sampled sera were decreased by an absorption test with
      anti-mite specific IgG antibody, and increased by reaction with an adequate
      volume of mite allergen. These facts indicate that circulating immune complexes
      are an anti-complementary factor working on the complement system, as previously
      reported, and that mite allergen and anti-mite IgG antibody relate to their
      conformation in status asthmatics. Clinically, MPS might possess an inhibitory
      effects on the formation of immune complexes and/or accelerate complement
      dependent solubilization of antigen-antibody complexes, so that anti-mite
      specific IgG antibody increased markedly in the peripheral blood.

PMID- 8279966
TI  - [Analysis of differential cell counts of sputa induced by inhalation of
      ultrasonically nebulized hypertonic saline or distilled water in asthmatic
      patients].
AB  - Bronchial asthma is an inflammatory disease of the airways, and a simple method
      of evaluating inflammation, safer than BALF or bronchial mucosal biopsy, has long
      been sought after. The induction of sputa by the inhalation of an appropriate
      solution and the examination of the induced sputa may provide such a method. We
      compared the safety of two sputum induction methods, ultrasonically nebulized
      hypertonic saline inhalation and distilled water inhalation, and examined the
      usefulness of differential cell counts of the induced sputa. The safety of these
      methods was ascertained by determining lung functions (FEV1.0, PEFR) and urinary
      leukotriene E4 before and after inhalation of these solutions, and the usefulness
      of differential cell counts of induced sputa by examining the
      uniformity/reproducibility. Only after the inhalation of distilled water did the
      lung function reveal a statistically significant decrease when the data were
      compared with the control values for each of the two methods (p < 0.01), and when
      the data obtained with distilled water inhalation and hypertonic saline
      inhalation were compared (p < 0.05). The urinary leukotriene E4 levels obtained
      were not very different between the two methods; however, in two patients,
      urinary leukotriene E4 levels were increased markedly only after inhalation of
      distilled water. The uniformity of the sputum differential cell counts in the
      same specimen (evaluated by intraclass correlation coefficient) and inter
      specimens (evaluated by Friedman test) was satisfactory for both methods, except
      for basophils. Hypertonic saline inhalation at 24-hour intervals gave a better
      reproducibility in differential cell counts of the induced sputa (evaluated by
      interclass correlation coefficient), when compared with distilled water
      inhalation. These results suggest that hypertonic saline inhalation is safer and
      more useful than distilled water inhalation for induction of sputum in a uniform
      and reproducible way, and that the induction of sputum by hypertonic saline
      inhalation will be clinically useful in asthmatic patients who cannot expectorate
      sputa spontaneously.

PMID- 8279967
TI  - [Inhibitory effects of AA-2414, a thromboxane (Tx) A2 receptor antagonist, on U
      46619-, prostaglandin (PG) D2- and 9 alpha, 11 beta PGF2-induced contractions of
      guinea pig tracheas and isolated human bronchi].
AB  - The effects of a novel TXA2 receptor antagonist, AA-2414 [(+-)-7-(3,5,6-trimethyl
      1,4-benzoquinone-2-yl)-7-phenyl-heptanoic acid], on U-46619-, PGD2- and 9 alpha,
      11 beta-PGF2 alpha-induced contractions of isolated guinea pig tracheas and human
      bronchi were investigated. AA-2414 competitively inhibited the contractile
      responses of both human and guinea pig preparations induced by U-46619 with
      similar pA2 values (7.7 and 7.6, respectively). In addition, the compound also
      inhibited the contractions of both preparations caused by PGD2 and 9 alpha, 11
      beta-PGF2 alpha, the IC50 values of which were 1.2 x 10(-7) and 1.8 x 10(-7) M in
      guinea pig tracheas and 2.8 x 10(-8) and 8.5 x 10(-8) M in human bronchi. These
      results suggest that AA-2414 may be a therapeutically useful drug for bronchial
      asthma.

PMID- 8279968
TI  - [Induction of IgE-Fc receptor (Fc epsilon RII/CD23) expression on stimulated
      monocytes by mite allergen in patients with asthma].
AB  - The low affinity IgE-Fc receptors (Fc epsilon RII/CD23) show an important role in
      atopic disorders such as bronchial asthma. Since monocytes/macrophages could be
      contributed to allergic inflammation through IgE stimulation, I examined Fc
      epsilon RII/CD23 expression on peripheral blood monocytes in patients with
      bronchial asthma. The expression of Fc epsilon RII/CD23 on monocytes was higher
      in asthmatic patients than in normal control subjects. Furthermore when
      peripheral blood monocytes in patients with mite-allergic asthma (RAST score > or
      = 3) were additionally stimulated by mite allergen, the expression of Fc epsilon
      RII/CD23 increased and remained after culture with mite allergen. In order to
      investigate the mechanisms of the induction of Fc epsilon RII/CD23, I examined
      the effects of the supernatants on Fc epsilon RII/CD23 expression on monocytes,
      using the monocytic cell line U937. Our findings were that the supernatants of
      mononuclear cells from mite allergic patients cultured with mite-allergen, as
      well as IL-4, induced Fc epsilon RII/CD23 expression on U937 cells, while anti IL
      4 antibody almost but not completely inhibited the induction of Fc epsilon
      RII/CD23 expression on U937 cells by the supernatants, suggesting a possibility
      that Fc epsilon RII/CD23 expression on monocytes might be mainly regulated by IL
      4 in combination with various cytokines.

PMID- 8279969
TI  - [Airway inflammatory cell dynamics during late asthmatic reactions induced by
      toluene diisocyanate in guinea pigs. II. Histological study].
AB  - We investigated airway inflammatory cell dynamics during late asthmatic reactions
      (LAR) induced by toluene diisocyanate (TDI) in a guinea pig model developed by K.
      Tanaka et al. (Bull. Chest Dis. Res. Inst. Kyoto Univ. 1983: 16: 1-9). For
      sensitization, 10% TDI solution was applied once daily to the bilateral nasal
      mucosa of 41 guinea pigs for 7 consecutive days. One week after the
      sensitization, the animals were challenged with 5% TDI solution once a week. In
      addition, metyrapone (50 mg/kg) was injected intraperitoneally 24 h, and 30 min
      before the challenge, respectively. Airway tissue specimens (large bronchi and
      bronchioles) were obtained from the 41 guinea pigs at each time point (30 min, 3,
      6, 24 and 168 h) after the challenge. Airway inflammatory cell dynamics were
      evaluated with regard to the onset and persistence of LAR. As a control, 7 guinea
      pigs were only exposed to ethyl acetate (a solvent for TDI) and sacrificed 6 h
      afterward. A histological examination of the airways revealed remarkable
      infiltration of eosinophils but failed to demonstrate infiltration of other
      inflammatory cells, including neutrophils, in the mucosal tissues of the bronchi
      and bronchioles during LAR at any time point (3, 6 and 24 h) after the challenge.
      Therefore, we conclude that eosinophils, but not neutrophils, play an important
      role in LAR in our model, a contrast to previous reports on human TDI-induced LAR
      in which neutrophils were also involved.

PMID- 8279970
TI  - [Hypersensitivity to apple pulp among patients with birch pollinosis in
      Hokkaido].
AB  - We evaluated the relationships between hypersensitivity to apple pulp and birch
      pollinosis in Hokkaido. 1. Seventeen (20%) of 83 patients with birch pollinosis
      (symptom and CAP positive) were revealed to be hypersensitive to apple pulp,
      which was a higher rate than that found in patients with other pollinoses. 2.
      Among the patients with birch pollinosis, the higher was the CAP score of birch
      pollen, the higher was the incidence of hypersensitivity to apple pulp.

PMID- 8279971
TI  - [Analysis of immunosuppressive activity of lecithin-bound iodine (LBI) on antigen
      induced IL2 responsiveness in peripheral blood lymphocytes from patients with
      allergic diseases].
AB  - The effect of lecithin-bound iodine (LBI) on antigen-induced IL2 responsiveness,
      useful in in vitro test for the detection of etiological antigen and disease
      activity in allergic diseases, was investigated. In peripheral blood mononuclear
      cells (PBMC) from asthmatic children, LBI suppressed Dermatophagoides farinae
      (Df)-induced IL2 responsiveness in a dose dependent manner, in a range of 0.01 to
      100 micrograms/ml. Similarly, LBI also suppressed ovalbumin (OVA)-induced IL2
      responsiveness in PBMC from patients with atopic dermatitis, sensitized with OVA,
      in concentration of 0.1 to 100 micrograms/ml. Moreover, purified protein
      derivative (PPD)-induced IL2 responsiveness was equally inhibited by LBI, at
      doses of between 0.1 and 100 micrograms/ml. However, LBI could not overcome the
      responses induced by concanavalin A (Con A) until it reached unphysiological
      concentrations of as high as 100 micrograms/ml. The fact that antigen-induced IL2
      responsiveness was suppressed by LBI at concentrations comparable to blood levels
      of LBI in individuals medicated suggests that LBI is a weak immunosuppressant.
      IL2-responding T cells were more sensitive to LBI than antigen-presenting cells
      in Df-induced IL2 responsiveness, although LBI suppressed both cell populations.
      Taken together, LBI could work as a weak immunosuppressant to inhibit lymphocyte
      responses to allergen and to improve clinical status in allergic diseases,
      including bronchial asthma caused by Df and atopic dermatitis provoked by OVA.

PMID- 8279972
TI  - High serum soluble interleukin-2 receptor concentrations in elderly individuals
      and smokers.
AB  - The effects of sex, age, and smoking on the serum concentrations of soluble
      interleukin-2 receptor (sIL-2R) were investigated in 83 healthy subjects. No sex
      related difference was found. The correlation between age and the serum sIL-2R
      concentration was weak, but significant, in the nonsmokers (r = 0.30, n = 50, p <
      0.05). The serum sIL-2R concentration was significantly higher in smokers than in
      nonsmokers (41.0 +/- 2.8 pM (mean +/- SEM), n = 33, vs. 31.9 +/- 1.0, n = 50, p <
      0.005). These results suggest that age and smoking habits should be taken into
      consideration when interpreting the serum sIL-2R concentration, although the
      mechanism by which sIL-2R concentrations are altered remains unknown at present.

PMID- 8279973
TI  - [Three cases of anaphylaxis by tannalbin].
AB  - We reported 3 cases of patients developed moderate to severe anaphylactic
      reaction induced by tannalbin as anti-diarrhoeic. Specific IgE-mediated
      hypersensitivity to tannalbin was demonstrated by history, prick skin test, RAST
      and Immunoblotting. We also certified that tannalbin is composed by tannic acid
      and casein using HPLC and SDS-PAGE.

PMID- 8279974
TI  - [Prevalence of electrocardiographic abnormalities in 2,000 aged and non-aged
      chagasic patients].
AB  - PURPOSE: To assess the prevalence of main electrocardiographic alterations in
      chagasic patients at University of Triangulo Mineiro Medical School, and compare
      such alterations between aged and non-aged patients. METHODS: Electrocardiograms
      (ECG) of 2,000 chagasic patients were interpreted. Age, color, sex and
      concomitant systemic hypertension, congestive heart failure (CHF) and
      megaesophagus and/or megacolon were registered. Chi-square test was employed to
      compare aged (60 years or more; n = 378) and non-aged (age less than 60 years; n
      = 1622) chagasics. RESULTS: ECG were normal in 9.6% of the patients. The main
      alterations were: ventricular premature complexes (VPC) 42.2%, left ventricular
      enlargement (LVE) 38.8%, right bundle branch block (RBBB) 32.4%, left anterior
      hemiblock 29.2% and ventricular repolarization changes 28.2%. The aged group
      exhibited greater (p < 0.05) proportion of male patients (1.7:1 vs 1.1:1), white
      than non-white (3.6:1 vs 2.2:1) and larger percentages (p < 0.01) of systemic
      hypertension (18.2 vs 7.5) and CHF (26.4 vs 12.0). The following alterations were
      significantly more common on aged chagasic: VPC (62.7 vs 37.5), LVE (43.4 vs
      37.1), atrial fibrillation (19.6 vs 5.5), supraventricular premature complexes
      (11.9 vs 5.2), electrically inactive zone (9.5 vs 6.6), wandering atrial
      pacemaker (4.5 vs 2.2) and 2nd-degree atrioventricular (AV) block (2.9 vs 1.5).
      The non-aged chagasic had greater percentage (p < 0.05) than aged group of normal
      ECG (10.7 vs 5.0), RBBB (34.1 vs 24.9) and 1st degree AV block (9.7 vs 6.3).
      CONCLUSION: There was a high prevalence of ECG alterations in chagasic patients
      seeking medical attention. The different frequencies of those alterations between
      aged and non-aged chagasic may result of conditions more frequently seen in aged,
      like ischemic heart disease, CHF and systemic hypertension or to a probable more
      severe cardiac denervation in non-aged chagasic.

PMID- 8279975
TI  - [Radioisotopic mapping of the arrhythmogenic focus in patients with chronic
      chagasic cardiomyopathy and sustained ventricular tachycardia].
AB  - PURPOSE: To localize the site of the origin of sustained ventricular tachycardia
      in chronic chagasic cardiomyopathy patients refractory to antiarrhythmic therapy
      by radionuclide angiography techniques. METHODS: Five patients underwent
      radionuclide angiography by intravenous administration of 25mCi 99mTc. The images
      were obtained in sinus rhythm and during sustained ventricular tachycardia
      induced in the electrophysiologic laboratory for endocardial mapping. Amplitude
      and phase images were obtained resulting in a contraction wave synchronic to
      ventricular dispolarization. RESULTS: All patients had haemodynamic stability
      during the arrhythmia. One patient had incessant ventricular tachycardia. Mean
      ejection fraction was 0.38. In 4 patients the site of the origin of ventricular
      tachycardia was posterior and in one it was localized in the interventricular
      septum. There was identity in the site of the origin of ventricular tachycardia
      obtained by endocardial mapping or radionuclide angiography in all patients. The
      therapy was chemical ablation in 3 patients, surgical aneurysmectomy in one and
      pharmacologic therapy in the last patient. CONCLUSION: The site of the origin of
      ventricular tachycardia can be estimated by analyzing the contraction wave
      obtained by radionuclide angiography techniques in patients with hemodynamic
      stable sustained ventricular tachycardia.

PMID- 8279976
TI  - [Pulse therapy (high doses of venous methylprednisolone) in children with
      rheumatic carditis. Prospective study of 40 episodes].
AB  - PURPOSE: To use corticosteroids in a shorter period to treat rheumatic carditis,
      keeping the patient in the hospital; and verify the time interval of
      normalization of rheumatic activity tests with this method. METHODS: In 36
      patients (40 episodes) intravenous methyl-prednisolone (1g/day) was administered.
      The number of series ranged from two to four, according to severity of the
      disease. The ages ranged from 6 to 17 years old, all of them fulfilled the
      criteria of Jones for diagnosis of rheumatic fever. They were submitted to
      treatment to eradicate the streptococcus, worms, PPD and dental focus extraction,
      before use of corticosteroids. RESULTS: In all patients the signals and symptoms
      of heart failure improved. In six cases occurred complications during pulse
      therapy that were easily controlled with clinical measures. Two series of
      methylprednisolone were used in 10 children, three in nine and four in 21
      episodes. Eight patients were sent to valve replacement. The interval of time
      that laboratory tests of rheumatic activity became negative was 41.2 +/- 13.3
      days. CONCLUSION: Using this IV corticotherapy it was possible decrease the
      amount of days of this medication, keeping the patient in the hospital. In this
      way we eliminate the problem of interruption of the treatment. There was not
      significative difference between oral and IV corticotherapy in order to the
      laboratory tests become negative.

PMID- 8279977
TI  - [Echocardiographic relation criteria. A new selection method for mitral valvotomy
      with balloon catheter].
AB  - PURPOSE: To find out new subjects that could be useful to select patients between
      9 and 12 points, according to Block's Criteria, to mitral balloon valvotomy.
      METHODS: One hundred and forty patients underwent mitral balloon valvotomy. Among
      them, 29 (21%) had between 9 and 12 points. These patients were divided into two
      groups: group A-patients with mitral valve area > or = 1.5cm2, immediately after
      balloon valvotomy and in the follow-up period; group B-patients with mitral valve
      area < 1.5cm2 immediately after or during the follow-up period, patients with
      severe mitral regurgitation after the procedure and patients who died in the
      follow-up period. All patients were analyzed by echocardiographic relation
      criteria (ERC): calcification + subvalvar disease/thickness + mobility. Each one
      was quantified from 1 to 4 points according to the degree of valvular disease.
      RESULTS: Group A was composed of 17 (51%) and group B 12 (41%) patients. The
      variables age, sex, previous mitral commissurotomy and atrial fibrillation did
      not show difference between groups. In group A mitral valve area (cm2) increased
      from 1.15 +/- 0.25 to 1.97 +/- 0.26 (p < 0.00001) keeping stable during the
      follow-up period. In group B percutaneous mitral balloon valvotomy resulted in an
      increase from 1.26 +/- 0.19 to 1.77 +/- 0.16 (p < 0.00001), however, there was an
      important decrease in the follow-up period to 1.34 +/- 0.15 (p < 0.00001). The
      ERC showed that all group A patients had a relation < 1. However, in group B, 10
      patients (83%), the relation was > or = 1, and in only 2 patients (17%) was < 1
      (p < 0.00001). CONCLUSION: The group of patients between 9 and 12 points in the
      Block's criteria is heterogenic, therefore, each case might be evaluated
      individually and the echocardiographic relation criteria should be used in order
      to select these patients to the procedure.

PMID- 8279978
TI  - [Catheter ablation of accessory pathways with low energy. Results in 40
      consecutive patients].
AB  - PURPOSE: To evaluate the results of direct current catheter ablation of accessory
      pathways by mean of a new low energy power source. METHODS: Catheter ablation was
      performed in 40 consecutive patients (23 male, mean age 31 +/- 11 years) with
      accessory atrioventricular pathways (AP) using a low energy DC power source. The
      electrophysiologic study and AP ablation were performed in the same procedure by
      endocardial approach using non-deflectable 6F bi, tri, or quadripolar electrodes.
      RESULTS: AP was located at left free wall (LFW) in 22 patients (55%),
      posteroseptal (PS) in 11 patients (27.5%), anteroseptal (AS) in 5 patients
      (12.5%) and right lateral (RL) in 2 patients (5.0%). A mean of 7.7 +/- 7 catodal
      shocks of 5-75 (20) joules (J) was delivered in 1.45 +/- 7 sessions, with a mean
      cumulative energy of 178 +/- 213J per patient. The mean values of number of
      shocks, number of sessions and cumulative energy per patient were lower in LFW AP
      ablation than in other positions (5 +/- 4 x 11 +/- 8 - p = 0.008; 1.1 +/- 0.3 x
      1.8 +/- 0.9 - p = 0.008 and 118 +/- 150 x 260 +/- 245 - p = 0.03). The mean CK-MB
      rise was 18.5 +/- 7.8U/1. Three patients (7.5%) presented hemopericardium after
      PS AP ablation and in 1 patient (2.5%), a PS AP (paranodal pathway) ablation
      resulted in total atrioventricular block. During a follow-up of 9.5 +/- 4 months
      AP was absent in 28 (70%) patients; 18/22 (82%) with LFW AP, 6/11 (54%) with PS
      AP, 3/5 (60%) with AS AP and 1/2 (50%) with RL-AP, (p = 0.10). CONCLUSION: Low
      energy DC ablation is effective for AP ablation. The results are related with AP
      position.

PMID- 8279979
TI  - [Hemodynamic variable analysis in patients with systemic arterial hypertension
      undergoing physical exercise].
AB  - PURPOSE: To verify the exercise-induced hemodynamic changes in moderate
      hypertensive patients. METHODS: Twenty nine patients were studied and they were
      submitted to cycloergometer supine exercise (50w and 100w) during cardiac
      catheterization. The hemodynamic variables were measured: cardiac index (CI),
      stroke volume (SV), systemic arterial resistance (SAR), pulmonary arterial
      resistance (PAR), wedge pressure (WP), right atrial pressure (RA), systolic
      arterial pressure (SP), diastolic arterial pressure (DP), mean arterial pressure
      (MP) and heart rate (HR). To evaluate the cardiac function, the patients were
      divided in two groups: GI with CI > 2.5 ml/min/m2 and GII CI < 2.5 ml/min/m2.
      RESULTS: During exercise, patients from GI and GII were similar-according to MAP,
      RA, WP, and HR. On the other hand, GI and GII exhibited different (#) behavior
      regarding SV, PAR and SAR. During the three exercise conditions, rest (R), 50w
      and 100w it was observed: a) PAR-R = 50 = 100 (GI); b) MP, PAR, WP, SV, SAR-R #50
      #100 (GI); c) HR, PAR and SAR-R #50 #100 (GII). There was no correlation between
      the cardiac function (CI, SV) and the circulatory adjustment (PAR and SAR) or the
      pressure curve (SP, DP, MP) and HR. CONCLUSION: The results suggest that the
      cardiac function of GI patients depends, mainly, on the inotropism, while in GII
      patients it depends on the decrease of the afterload (PAR and SAR). Those changes
      may appear even in the late exercise stage (100w), with a bias to attain the GI
      levels. Those observations suggest functional changes in vasomotor tone of GII
      patients.

PMID- 8279980
TI  - [Acute occlusion after coronary angioplasty. Early management and late course].
AB  - PURPOSE: Assess the efficacy of the different strategies employed in the
      management of acute closure and verify the late prognosis of patients who develop
      this complication. METHODS: From january 1987, through December 1990, 2315
      consecutive patients underwent percutaneous transluminal coronary angioplasty
      (PTCA) in our Institution. We analyzed 100 patients who had had acute closure of
      the dilated vessel determining the total incidence of myocardial infarction and
      death, the effectiveness of the different treatment strategies and clinical and
      angiographic predictors of poor in-hospital outcome. Late follow-up was obtained
      in the hospital survivors. RESULTS: The incidence of acute myocardial infarction
      in the group of 100 patients was 57%; death occurred in 12% of the patients.
      Forty-one individuals were referred to emergency bypass surgery, 35 received
      clinical treatment and 24 underwent redilatation of the vessel. Those managed
      clinically had a higher incidence of myocardial infarction compared to the ones
      who underwent either redilatation or surgery (74.3% versus 50% and 48.8%). The in
      hospital mortality rate was significantly higher in patients with left
      ventricular ejection fraction < 45% (44.4%, p < 0.001) and in procedures
      involving the left anterior descending artery (20%, p < 0.05); patients
      undergoing repeat dilatation had the lower death rate (4.2% versus 8.6% in the
      clinical group and 17.1% in the surgical group). Late follow-up was obtained in
      65 of 88 hospital survivors (mean follow-up = 17 months). Patients who underwent
      repeat dilatation were significantly less symptomatic in the follow-up than those
      who received medical therapy during the acute phase (89% versus 60.9% of patients
      without symptoms respectively, p < 0.05). Patients who were referred to surgery
      had also a tendency towards having less symptoms (87.5% of asymptomatic patients
      in the late follow-up) although the difference was not statistically significant
      (0.01 > p > 0.05). CONCLUSION: Acute coronary occlusion is a serious complication
      of angioplasty and is associated with high rates of major complications
      (myocardial infarction, death). Low left ventricular ejection fraction and PTCA
      involving the left anterior descending are predictors of higher in-hospital
      mortality in patients with acute closure. Late outcome is less favourable in
      patients submitted to clinical treatment in the acute phase.

PMID- 8279981
TI  - [Chronotropic and pressoric response in myocardiopathy in patients with heart
      failure during ergometric test. Correlation of spirometry variables with effort].
AB  - PURPOSE: To correlate the variables heart rate (HR), blood pressure (BP) and
      double product (DP) during the ergometric test with the variables oxygen
      consumption (VO2) and pulmonary ventilation (VE) of spiroergometry. METHODS: A
      study was carried out with 40 male patients suffering from cardiomyopathy with
      heart failure (functional class II-IV of NYHA)-of ischemic (IS), Chagas' disease
      (CH) and idiopathic (ID) etiology. These three groups were compared to a group of
      10 normal individuals (N). The 4 groups were evaluated under 4 different
      conditions: rest (RES), anaerobic threshold (LA), power peak of exercise (P) and
      in the fourth minute recovery (REC). The investigation was carried out with the
      data obtained through spiroergometry (using a treadmill and spiroergometric
      equipment specific for the effort), as well as data related to HR, BP, DP, VO2
      and VE. RESULTS: There were significant differences observed in the ergometric
      evaluate of the HR, BP and DP responses in the IS, CH and ID groups as compared
      with the N group. There were significant difference observed in the spirometric
      evaluation to the VO2 and VE efforts in the IS, CH and ID groups as compared with
      the N group. CONCLUSION: The HR, BP and DP variables studies, obtained by means
      of classic ergometry, unaided by direct methodology (spiroergometry) enabled them
      to infer valuable data for the control and evaluation of cardiomyopathies with
      IC, taking into consideration the low chronotropic and pressoric responses in the
      various phases of evaluation during this study, corresponding to the concomitant
      low performance of O2 consumption and pulmonary ventilation.

PMID- 8279982
TI  - [Atriofascicular connection with slow conduction and longitudinal dissociation.
      Electrophysiologic evidence and clinical implications].
AB  - We report on a patient with paroxysmal left bundle branch block-like tachycardia
      with electrophysiologic findings suggestive of nodoventricular pathway
      (ventricular pre-excitation dependent on slowing of AV conduction, and accessory
      pathway with exclusive anterograde conduction). There was no pre-excitation
      during sinus rhythm but it was brought on by intravenous verapamil.
      Atrioventricular node conduction curves showed no signs of duality. Diagnosis of
      an atriofascicular pathway with decremental properties was based on the following
      findings: 1) absence of AV dissociation during reciprocating tachycardia; 2)
      absence of fusion beats or narrowing QRS complexes during tachycardia; 3)
      advancement of right ventricular activation with late atrial extrastimuli
      delivered during antidromic tachycardia at a time of low right atrium
      refractoriness; 4) observation that earliest ventricular endocardial electrogram
      during tachycardia (activation mapping) was simultaneous with the right bundle
      potential; 5) surgical ablation of the accessory pathway by endocardial incision
      at the right anterior aspect of the tricuspid ring, far away from the AV node
      region. Evidences showing anterograde longitudinal dissociation of the accessory
      pathway included cycle length alternation during tachycardia and duality of
      accessory pathway conduction times and refractory periods. We hypothesize that
      reentry occurring in such AV node-like structure could give to a pre-excited
      tachycardia with AV dissociation mimicking antidromic tachycardia associated with
      nodoventricular pathway.

PMID- 8279983
TI  - [Right ventricular rhabdomyoma causing pulmonary stenosis].
AB  - The authors report a case of rhabdomyoma of the right ventricular cavity with
      outlet obstruction in a three-months old infant. The diagnosis was established by
      echocardiography. Bidimensional echocardiography study showed a polypoid tumor of
      the right ventricle. During the systole it was projected through the pulmonary
      valve, obstructing part of it. The Doppler study showed an important gradient
      between the right ventricle and the pulmonary artery. The resection was performed
      with success. The diagnosis of cardiac rhabdomyoma was made by microscopic study.
      It is emphasized the importance of the echocardiographic study in an infant with
      oligosymptomatic cardiac murmurs.

PMID- 8279984
TI  - [Ebstein's anomaly associated with interventricular communication].
AB  - Twelve-year-old patient, with congestive heart failure and mild, caused by
      Ebstein's anomaly with interventricular septal defect, was studied and submitted
      to surgical correction which consisted in covering the interventricular defect
      with a path of bovine pericardium and substituting for the tricuspid valve with a
      biological prosthesis (porcine). After surgical correction, the patient was
      submitted to strict clinical and laboratorial (echocardiogram and cardiac
      catheterization) evaluation which presented excellent adjustment of the cardiac
      antriums, with improvement of myocardial function index. The problems related to
      the diagnosis of the association of the Ebstein's anomaly with interventricular
      septal defect can be solved with a well done semiology, helped by accurate
      laboratorial procedures like echodopplercardiogram and cardiac catheterization.
      The total surgical correction can be achieved with results and, with this fact,
      change the natural development of the disease.

PMID- 8279985
TI  - [Platelet activation and arterial thrombosis].

PMID- 8279986
TI  - [Effect of treatment with chlorthalidone on reduction of left ventricular mass in
      patients with systemic arterial hypertension].
AB  - PURPOSE: To evaluate the effects of the use of chlorthalidone on left ventricular
      mass of patients with mild and moderate systemic arterial hypertension (SAH).
      METHODS: Twenty-nine patients with mild and moderate SAH were studied with mean
      age of 48.4 years and 16 men. Clinical evaluation, systolic (SBP) and diastolic
      (DBP) blood pressure and heart rate (HR), in supine and standing positions, were
      obtained before and every 3 weeks, after 2 with placebo, during 12 weeks of
      treatment with 50mg of chlorthalidone each 48 hours. Laboratory data (hemogram,
      sodium, potassium, urea creatinine, glucose, hepatic aminotransferases and
      urinalysis) were done before and at end of study. Echocardiographic study was
      performed by M-mode before and after 6 and 12 weeks of treatment, and obtained
      the following data: diastolic diameter (DdLV), diastolic septum (DSTLV) and
      posterior wall thickness (PWTLV) of left ventricle. The left ventricular mass
      (LVM) was calculated by the formula: LVM = (DSTLV+PWTLV+DdLVE)3 - (DdLV)3 x
      1.05/body surface, in g/m2. RESULTS: A significant reduction of SBP (p < 0.0001),
      DBP (p < 0.001) in supine and standing positions. HR did not show statistical
      difference. At echocardiographic study, M-mode, was observed a significant
      reduction of LVM after 12 weeks of treatment (181 +/- 67 to 156 +/- 34 g/m2, p <
      0.01). CONCLUSION: Chlorthalidone was effective to control blood pressure and to
      reduce LVM of patients with SAH.

PMID- 8279987
TI  - [Reductions in lipid fraction plasma levels induced by simvastatin and
      bezafibrate. Brazilian multicenter study].
AB  - PURPOSE: To compare the effects of simvastatin and bezafibrate on the lipid
      profile to attain the objectives proposed by National Cholesterol Education
      Program (NCEP). METHODS: One hundred twenty six hypercholesterolemic patients (69
      females and 57 men, 56.0 +/- 10.0 years old), after selection and placebo period
      (4 weeks) were maintained on lipid-lowering diet and were randomly assigned in a
      double-blind fashion to receive for 12 weeks, bezafibrate (B, 200mg t.i.d. - BG(n
      = 66)) or simvastatin (S, 10-40mg q.p.m. - SG(n = 60)). During the study, 28
      patients (SG0) received S 10mg; in 14 patients (SG1) dosage was titrated to 20mg
      and in 18 cases (SG2) to 40mg. Clinical examination, lipid profile and safety
      determinations, and adverse effects were assessed in different periods of the
      study. RESULTS: Mean profile analysis showed different behaviour of BG, SG0, SG1
      and SG2 through time for TC, TG, LDL-C and VLDL-C. Mean reductions of TC and LDL
      C were more marked in SG (30.3 and 40.9%) than in BG (18.8 and 24.8%). BG showed
      greater increase of TG (33.7%) and HDL-C (25.9%) than did SG (16.3 and 7.7%
      respectively). Reduction greater than 30% (optimal responses) and between 20 and
      29% (good responses) were more frequent in SG and LDL-C. BG showed greater
      frequency of good and optimal responses for TG reduction and HDL-C increase. NCEP
      goals were achieved in 75.4% of SG and 46.9% of BG (p = 0.001). No clinical or
      laboratorial adverse experiences were reported in any treatment groups.
      CONCLUSION: Simvastatin was more effective in the reduction of plasma levels of
      atherogenic lipid fractions (TC and LDL-C) and this treatment allowed earlier
      achievement of the goals proposed by NCEP in a greater number of patients.

PMID- 8279988
TI  - The distribution of cellular retinoic acid-binding protein I during odontogenesis
      in the rat incisor.
AB  - Retinoids are important molecules in various aspects of embryological
      development. Here the distribution of cellular retinoic acid-binding protein I
      (CRABPI) was studied in the continuously growing incisor of adult rats using an
      affinity-purified rabbit polyclonal antibody. CRABPI was present throughout the
      presecretory and secretory ameloblast layer. The protein disappeared from that
      layer during its maturation phase. The adjacent dental mesenchyme of the
      developing pulp stained positively for CRABPI, especially in the layer
      immediately beneath the fully differentiated odontoblasts. Little CRABPI was
      present in the odontoblast layer itself. The distribution of CRABPI, both in the
      undifferentiated basal region of the incisor tooth and associated with the cells
      during hard-tissue formation, suggests a role for this molecule during
      differentiation and hard-tissue genesis.

PMID- 8279989
TI  - A comparative ultrastructural study of the mitotic chondrogenic cells in the
      mandibular condyle and tibial growth plate of the rat.
AB  - Mitotic cells in the rat mandibular condyle (proliferative mandibular cells) were
      compared with mitotic cells in the rat tibial growth plate (proliferative tibial
      cells). In the tibial proliferative cells, the rough endoplasmic reticulum mostly
      became vacuolated during the latter stage of mitosis, whereas the rough
      endoplasmic reticulum of the proliferative mandibular cells rarely underwent
      disorganization. Further, a wide area remained outside of the mitotic spindle in
      the proliferative tibial cells at the metaphase, while only a narrow area
      remained in the proliferative mandibular cells. This finding might account for
      the difference of disorganization of the rough endoplasmic reticulum.

PMID- 8279990
TI  - The effect of propranolol on salivary gland function and dental caries
      development in young and aged rats.
AB  - Medications commonly used in elderly people cause hyposalivation and are
      associated with an enhanced prevalence of dental caries. Propranolol (a beta
      adrenergic antagonist) is a commonly used antihypertensive agent that is
      prescribed for long-term use. The purpose of this investigation was to compare
      the effects of this drug on salivary composition and flow rate, and on caries, in
      young and aged rats. Forty young (28-day) and 36 aged (20-month) female Sprague
      Dawley rats were infected with Streptococcus sobrinus 6715 and fed a cariogenic
      diet for 28 days. Propranolol was given in high (20 mg/kg/day) and low (10
      mg/kg/day) doses via osmotic pumps. Unoperated and desalivated animals served as
      controls. Smooth-surface caries scores in the young animals receiving propranolol
      at 20 mg/kg/day were statistically higher than in the young intact rats (p < or =
      0.05). Increased smooth-surface and sulcal caries scores were recorded in the
      aged propranolol-treated animals, but the differences were not statistically
      significant when compared with those in intact aged animals. Propranolol in aged
      animals did not affect the amount of alveolar bone loss but increased the risk of
      development of root caries. Young animals harboured greater populations of Strep.
      sobrinus and total cultivable flora than did all aged groups except the
      desalivated group. Salivary flow rates, induced by pilocarpine, were not
      decreased by the chronic administration of propranolol. Although the total
      protein concentration in parotid and submandibular saliva from drug-treated
      animals was reduced, differences were not observed in their SDS-PAGE profile when
      compared with unoperated animals. The findings demonstrate that chronic use of
      propranolol reduced the total protein concentration in saliva of all animals,
      increased caries susceptibility, but did not reduce the stimulated salivary flow
      rate.

PMID- 8279991
TI  - Effect of fluoride incorporation into human dental enamel on its demineralization
      in vitro.
AB  - Coronal surfaces of extracted human teeth were ground to a depth of about 1 mm
      and then cut in half labiolingually. One half was used as a control; the other
      half was exposed, for 3 days, to a fluoride-enriching buffer (0.1 mol/l lactic
      acid, 19.7 mmol/l CaCl2, 10.8 mmol/l KH2PO4, 3 mmol/l NaN3; pH adjusted to 4.68
      with KOH) having fluoride concentrations from 0.0002 to 2.2 parts/10(6). This
      exposure resulted in an uptake of fluoride by the enamel to a depth of 2 microns
      without any apparent demineralization. The fluoride uptake was proportional to
      the F concentration of the enriching solution, reaching concentrations of about
      8000 parts/10(6) within the first micrometre of enamel exposed to the highest F
      concentration; the controls had uniform F concentrations not exceeding 50
      parts/10(6) along the 2.5 microns of enamel depth sampled. Thin sections (140-160
      microns) were cut perpendicularly to the lingual surface, coated with protective
      resin except for a window about 1 mm long on the ground lingual surface, and
      exposed to a demineralizing buffer. The mineral losses of the sections were
      followed over 5 days by microradiography and image analysis. Fluoride enrichment
      resulted in reduced demineralization and the reduction was inversely related to
      the enamel fluoride content. The controls displayed a uniform erosion of the
      surface enamel whereas all the treatments below 1.5 parts/10(6) in the enriching
      solutions developed typical subsurface 'lesions'. The mineral content of the
      surface layer increased with increasing time of exposure to the demineralizing
      buffer.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279992
TI  - Lectin histochemical study of bovine lingual glands.
AB  - Bovine lingual glands consist of mucous acini capped by demilunes. Information on
      the chemical structure of their secretory glycoconjugates was obtained by means
      of a battery of peroxidase-conjugated lectins with affinity for specific terminal
      sugars. Sialidase procedures followed by lectin staining were also used to
      visualize the sugar sequences. Stored secretions in mucous acinar cells contained
      fucose, N-acetylglucosamine, alpha and beta-N-acetylgalactosamine as terminal
      sugar residues and beta-galactose as penultimate sugar in a heterogeneous
      distribution. Demilunar cells failed to react with any of the lectins examined
      except that of Dolichos biflorus.

PMID- 8279993
TI  - The effects of chewing-gum stick size and duration of chewing on salivary flow
      rate and sucrose and bicarbonate concentrations.
AB  - The objectives were to determine (1) the relations between salivary flow rate and
      the sample weights of chewing-gum and gum base, (2) whether any reduction in
      salivary flow rate with duration of chewing is due to a reduction in hardness of
      gum base with chewing, and (3) the sucrose and bicarbonate concentrations in
      saliva elicited by different weights of chewing-gum containing sucrose. Ten
      subjects chewed, for 20 min, samples of 1, 2, 3, 6 and 9 g of gum base and of a
      sucrose-containing chewing-gum. With each sample, salivary flow rates peaked
      initially and then fell to a relatively constant value. Flow rates during the
      periods of 1-2 and 15-20 min were linearly related to the logarithm of sample
      weight. With the chewing-gum samples, virtually all the sucrose was released into
      the saliva during the 20 min of chewing, with peak concentrations (201-666 mM) at
      1-2 min, and bicarbonate concentrations were higher with the 9-g than the 3-g
      samples. Six subjects chewed 3 g of gum base and within 45 min the weight of base
      had increased to 122% of the original, presumably due to the uptake of saliva.
      The hardness of gum base was determined at 21 and 36 degrees C, 21 and 36 degrees
      C after it had been chewed, and 21 degrees C after it had been chewed without
      exposure to saliva, and gave Brinell values of 0.277, 0.038, 0.022, 0.002 and
      0.061, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279994
TI  - Evans blue extravasation in rat dental pulp and oral tissues induced by
      electrical stimulation of the inferior alveolar nerve.
AB  - Whether increased extravasation of plasma protein may occur in the rat incisor
      pulp as a result of antidromic stimulation of afferent nerves was investigated,
      and this preinflammatory reaction compared with that in adjacent soft tissues. In
      anaesthetized rats, the inferior alveolar nerve was exposed and stimulated
      electrically (10-15 V, 2 ms, 10 Hz for 30 s or 5 min). Blood flow changes in the
      lower lip and incisor pulp were recorded by laser Doppler flowmetry. Increased
      vascular permeability in the lip, gingiva and pulp was indirectly determined by
      means of the Evans blue dye method and spectrophotometric analysis. Stimulation
      of the inferior alveolar nerve for 30 s, in the presence of the alpha-adrenergic
      blocker phenoxybenzamine (3 mg/kg), increased blood flow in the lip by 172 +/-
      16% and in the pulp by 38 +/- 5% as compared to basal blood flow. Intravenous
      (i.v.) administration of atropine (1 mg/kg), chlorisondamine (3 mg/kg), timolol
      (150 micrograms/kg), cimetidine plus mepyramine (3 mg/kg of each), methysergide
      (1 mg/kg) and diclofenac sodium (3 mg/kg) was without effect on this response.
      Acute pretreatment with capsaicin (1-3 mg/kg, i.v.), however, abolished the
      vasodilation in the pulp and reduced that in the lip by 58% (p < 0.05). In
      untreated animals, stimulation of the inferior alveolar nerve for 5 min increased
      the Evans blue content in the ipsilateral lip by 164% (p < 0.001), gingiva by 55%
      (p < 0.01) and pulp by 67% (p < 0.01). Pretreatment (i.v.) with a combination of
      cimetidine and mepyramine counteracted the dye extravasation only in the
      gingiva.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279995
TI  - Further evidence for a hypothalamus-parotid gland endocrine axis in the rat.
AB  - The existence of a hypothalamus-parotid gland endocrine axis that stimulates
      intradentinal dye penetration (IDDP) in rat teeth was suggested in earlier
      studies and IDDP-stimulating factors were isolated or purified from porcine
      parotid glands and hypothalamic tissues, respectively. In the present study,
      infusion of carbamyl-DL-aspartic acid (CAA) into rats was used to demonstrate the
      role of the endogenous hormones of the hypothalamus-parotid gland endocrine axis
      in stimulating IDDP, as observed by fluorescence microscopy of longitudinal
      sections of molar teeth. Intra-arterial infusion of CAA into intact rats
      stimulated IDDP in a dose-related fashion (between 49-390 nmol/100 g body
      weight); however, infusion of 390 nmol into parotidectomized rats was
      ineffective. Infusion of plasma from CAA-treated rats was equally effective in
      stimulating IDDP in intact and in parotidectomized animals. In contrast, plasma
      obtained from parotidectomized, CAA-treated rats stimulated IDDP in intact
      recipient animals but not in parotidectomized ones. Moreover, plasma from adult
      rats treated with CAA after an electrolytic lesion of the hypothalamus, and
      infused back into young intact rats, was ineffective in stimulating IDDP. These
      results indicate that: (1) CAA requires the functional integrity of the parotid
      gland to express its IDDP-stimulating activity, (2) a hormonal factor is secreted
      by the parotids in response to CAA stimulation and is directly responsible for
      IDDP stimulation, (3) release of the endocrine parotid IDDP-stimulating factor
      after infusion of CAA involves a second endocrine factor that appears to
      originate from the hypothalamus.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8279996
TI  - Partial sequencing of two forms of concanavalin A-unbound collagenase inhibitor
      from bovine gingiva.
AB  - Three forms of collagenase inhibitor, one ConA-bound and two ConA-unbound, were
      extensively purified from bovine gingiva by sequential column chromatography.
      Analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed
      that inhibitory activity resides in proteins with M(r) of 26000-28000 and 22000
      for ConA-bound and two ConA-unbound inhibitors, respectively. Of these, two ConA
      unbound inhibitors were partially sequenced in the first 12 amino acids and found
      to have an identical sequence. The NH2-terminal sequence had 100% identity with
      TIMP-2 or MI.

PMID- 8279998
TI  - Nutrition clinics.

PMID- 8279997
TI  - Cariogenic effect of caffeine intake during lactation on first molars of newborn
      rats.
AB  - Lactating dams with eight suckling pups were fed either a 20% protein diet as a
      control or experimentally a 20% protein diet supplemented with caffeine (2
      mg/100g body weight) from the birth of the pups to day 22. At day 22, the pups
      from both groups were weaned and fed a cariogenic diet until day 50, when they
      were killed. Dental caries of the molars were scored from randomized mandibles.
      The enamel of the first molars in the caffeine group showed significantly higher
      caries scores than that of the controls. This appears to be the first unequivocal
      evidence that caffeine is a cariogenic agent when newborns are exposed to it
      during critical periods of tooth development. Therefore, the widespread human
      consumption of caffeine could be a threat to the healthy development of teeth.

PMID- 8279999
TI  - The febrile patient.
AB  - Fever has long been recognised as a manifestation of infection; on occasions, it
      may be a pointer to other underlying diseases including immune-mediated and
      neoplastic conditions. This article explores the causes of fever, especially
      prolonged fever, and provides a management plan.

PMID- 8280000
TI  - Streptococcal update. A microbiology perspective.
AB  - The streptococci remain important human pathogens despite it being nearly 60
      years since sulphonamides were introduced. Rheumatic fever and post
      glomerulonephritis are common diseases in the Aboriginal community, and a new
      invasive disease, toxic shock-like syndrome, is also caused by Group A
      Streptococcus. Group B, first described over 50 years ago in obstetric wards
      remains the primary neonatal pathogen despite attempts to eliminate this organism
      from the genital tract of the carrier mother. A major concern in paediatrics is
      the relatively poor response to the current pneumococcal vaccines. Australian
      researchers are playing a major role in developing a new vaccine with high
      antigenicity against all of the 100 odd serotypes of S pneumoniae. The oral
      streptococci are now recognised as important opportunistic pathogens and the
      pathogenesis is well defined. Disturbing reports from different geographical
      regions alert us to the antibiotic resistance in some of the streptococci once
      thought of as sensitive bacteria, for example, Group A has shown resistance to
      erythromycin, the pneumococcus to penicillin and beta-lactam antibiotics and the
      aminoglycosides have been ineffective against the enterococci due to plasmid
      borne genes.

PMID- 8280001
TI  - The diagnosis and treatment of malaria in Australia.
AB  - The number of reported malaria cases is increasing each year with several deaths
      reported recently. This article reviews the types of malarias, including their
      incidence, prevention, presentation and the standard treatment protocols.

PMID- 8280002
TI  - Invasive Haemophilus influenzae type b disease.
AB  - In this overview, the characteristics of Haemophilus influenzae type b (Hib) as
      an organism and the important clinical and diagnostic features of the diseases it
      causes are discussed. Important developments in vaccination and in the treatment
      and prevention of Hib disease are outlined.

PMID- 8280003
TI  - Update on Ross River fever.
AB  - Ross River fever, or epidemic arthritis, is caused by the Ross River virus and
      usually mild and short-lived although persisting joint symptoms can develop. This
      article reviews the cause, diagnosis and treatment of this sometimes debilitating
      disease.

PMID- 8280004
TI  - Current concepts in asthma management.
AB  - This short paper investigates the effects of prophylaxis on re-admission rates at
      the Royal Alexandra Hospital for Children, Camperdown, New South Wales.

PMID- 8280005
TI  - Wound care initiatives.

PMID- 8280006
TI  - The Illawarra General Practice Training Unit. Teaching junior medical officers.
AB  - The Illawarra General Practice Training Unit, which has been functioning for more
      than four years, offers a model of general practice education that addresses some
      of the fundamental issues concerning the introduction of the young doctor to the
      realities of working in the community as well as providing a centre for GP
      research and continuing medical education (CME).

PMID- 8280007
TI  - The gentle art of feedback.
AB  - In itself giving feedback effectively is not difficult. However, it requires
      time, planning and good communication skills. It is labour-intensive. It is an
      essential part of supervision. Adequate supervision needs to be a high priority
      in all our teaching institutions. People do not learn by 'osmosis' as many claim.
      Learning can be accelerated and enhanced to a great degree by improving our
      feedback skills.

PMID- 8280009
TI  - Primary suture for excision of a small tumour.

PMID- 8280008
TI  - A pattern of decline in general practice obstetric care in Adelaide.
AB  - Some educational, training and politico-economic reasons for the decline in GP
      obstetrics in Adelaide, South Australia, are described. It is recommended that
      similar studies be done in other centres in Australia to evaluate the general
      nature of the findings.

PMID- 8280010
TI  - Pressure ulcers. A literature review and a treatment scheme.

PMID- 8280011
TI  - An elemental morning.
AB  - The completion of these four visits, the morning exchanges, was only the
      beginning of the day. I was not free to go home, but free to drive to the branch
      surgery and face the morning exchanges. Who knows what elements I would be
      encountering there. At least I could look forward to the end of the day. Tonight
      was the eve of St Andrew's, and the St Andrew's Society of Scotland would be
      having their annual dinner. There a few hundred Scots and Australians of Scottish
      background would be gathering to continue the tradition of celebrating their
      Scottish background while far from home. A noisy, flowing evening would be had by
      all.

PMID- 8280012
TI  - The GP--an instrument of change.
AB  - This commentary is not so much about Mr B's battle with alcohol dependency but
      the evolution of a doctor-patient relationship. It focuses more on some of the
      motivating forces involved in helping such patients improve their lifestyles.

PMID- 8280013
TI  - Various mixtures.
AB  - Australian Family Physician is pleased to present a home course in extemporaneous
      prescribing, an interesting area that is poorly understood by many practitioners,
      especially recent graduates. Dr. Bernard Kelly has been teaching this discipline
      to Family Medicine trainees in New South Wales for many years. A question is
      included at the end of each module.

PMID- 8280014
TI  - A real headache.

PMID- 8280015
TI  - Why I like rural practice.
AB  - Not all rural doctors have had a lifelong ambition to enter rural practice. For
      some the decision comes after a positive experience even quite late in their
      professional development. This paper is written by a rural doctor with little
      experience of rural life until he was posted to a small one-doctor community
      under the Queensland Government's State Fellowship scheme. Seven years later ...

PMID- 8280017
TI  - William Desmond (Bill) Jackson. Focus on rural practice.

PMID- 8280016
TI  - An audit of thrombolytic therapy in a rural hospital.
AB  - OBJECTIVE: To ascertain the complications from the use of streptokinase in a
      hospital remote from specialist support. DESIGN: A retrospective analysis from
      record files of patients treated with streptokinase thrombolysis following
      myocardial infarction. SETTING: Busselton District Hospital, Busselton, Western
      Australia. METHOD: The medical records of all patients admitted to Busselton
      District Hospital, from 1986 to 1991 with diagnoses of chest pain, angina or
      myocardial infarction were studied retrospectively and those admitted in 1992 who
      were given streptokinase were studied prospectively. RESULTS: Thirty-one patients
      received streptokinase. Two patients received this treatment twice. The drug was
      started a median of 30 minutes after arrival in casualty. Four deaths and one
      case of serious haemorrhage were recorded. CONCLUSION: Thrombolytic therapy is
      simple to give. Early use of it should be encouraged in isolated hospitals.

PMID- 8280018
TI  - Appendicitis: some observations.

PMID- 8280019
TI  - Mammographic screening.

PMID- 8280020
TI  - Fighting Haemophilus influenzae type b.

PMID- 8280021
TI  - Equine bronchoalveolar lavage cytology: survey of thoroughbred racehorses in
      training.
AB  - Sixty-two Thoroughbred horses aged between 1 and 7 years in training in Sydney
      had bronchoalveolar lavage (BAL) samples collected for cytological examination.
      All horses, except the yearlings and those with a cough, had raced at the time of
      the examination and the trainers reported satisfactory performance. Free
      erythrocytes were found in 73% of samples and haemosiderophages in 90% of the
      samples, indicating immediate or past occurrences of exercise-induced pulmonary
      haemorrhage (EIPH). Bronchoalveolar fluid from the yearlings contained
      significantly less (P < 0.05) erythrocytes and haemosiderophages than samples
      from horses in other age groups. In the older horses, there was also more
      haemosiderin within the macrophages. No differences in BAL cytology could be
      attributed to gender, and there was no relationship between BAL cytology and
      racing performance. The main cytological findings were (mean +/- sd): total
      nucleated cells--832 +/- 578/microL with the main cell types being: macrophages-
      59 +/- 10% (haemosiderophages--20 +/- 24%); neutrophils--9 +/- 6%; lymphocytes-
      31 +/- 9%. The erythrocyte count was 10.3 +/- 17.7% of the total cell count.
      Horses with chronic coughing had a higher proportion of macrophages and a lower
      proportion of lymphocytes in the leucocytes obtained from BAL. There was a higher
      occurrence of EIPH detected in BAL findings than that previously reported when
      endoscopic examination has been used to diagnose EIPH. The occurrence and
      severity of EIPH as indicated by the BAL findings was found to be related to
      exercise intensity. The cytological findings were similar to those reported in
      horses in the northern hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280022
TI  - Clinical, diagnostic and biochemical features of generalised glycogenosis type II
      in Brahman cattle.
AB  - Clinical, diagnostic and biochemical features of generalised glycogenosis are
      described in 96 Brahman-type calves. Typically the calves were presented when
      about 6 months of age, with ill-thrift and muscular weakness as the most common
      signs. Acidic alpha-glucosidase activity was reduced in peripheral blood
      lymphocytes and skeletal muscle. Muscle glycogen concentration was consistently
      higher in affected animals than in clinically normal cattle. Other observations
      in affected calves included elevation of serum aspartate aminotransferase and
      creatine kinase activities and excessive amounts of high molecular weight
      oligosaccharides in urine. Fine cytoplasmic vacuolation of neurones in the brain
      and spinal cord, skeletal muscle, myocardium and of Purkinje fibres were
      consistent histological observations. Periodic acid-Schiff staining revealed the
      presence of glycogen-like material in peripheral blood lymphocytes of all
      affected calves, indicating that this is a useful aid for the diagnosis of
      glycogenosis. While 3 of the 96 calves showed somewhat different clinical signs,
      the similarity of pathology and the biochemical and clinical evidence in the
      remainder suggested that, in these animals, the disease was expressed as a single
      syndrome.

PMID- 8280023
TI  - Euthanasia; not always eu.

PMID- 8280024
TI  - Oesophageal compliance in naturally occurring canine megaoesophagus.
AB  - The passive biomechanical property of oesophageal compliance (OC) was measured in
      8 naturally occurring cases of canine megaoesophagus, 8 matched control and 7
      vagotomised control dogs. Of the 8 dogs with megaoesophagus, 6 had congenital
      idiopathic megaoesophagus and 2 had secondary megaoesophagus attributable to
      generalised skeletal muscle disease. Stepwise distension of the whole oesophagus
      was employed for measurement of OC at the 4.0 and 8.0 mL/kg injected volume steps
      within the control volume range (0 to 12.0 mL/kg). At both injected volume steps
      OC was higher in megaoesophagus dogs than in either matched control or
      vagotomised control dogs (P < 0.01 in both cases), and no significant difference
      was observed in OC between matched control and vagotomised control dogs. No
      correlation was demonstrated between OC and the estimated duration of clinical
      signs of dogs with megaoesophagus. These findings suggest that in most cases of
      canine megaoesophagus the viscoelastic properties of the oesophageal wall are
      significantly altered, that in such cases the disorder is unlikely to be purely
      dynamic and that processes other than the duration of oesophageal dilatation are
      responsible for the alteration in oesophageal wall biomechanical properties. The
      relevance of these findings to current concepts on pathophysiological mechanisms
      underlying the evolution and resolution of various forms of canine megaoesophagus
      is discussed.

PMID- 8280025
TI  - Amoebic meningoencephalitis in a young grey kangaroo (Macropus giganteus).

PMID- 8280026
TI  - The effect of moxidectin against benzimidazole- and levamisole-resistant
      nematodes of sheep in Western Australia.

PMID- 8280027
TI  - Preliminary investigations into the feasibility of freezing koala (Phascolarctos
      cinereus) semen.

PMID- 8280028
TI  - Ventricular septal defect and an atrioventricular valvular anomaly in a heifer.

PMID- 8280029
TI  - Chlamydial infection in koalas under relatively little alienation pressure.

PMID- 8280030
TI  - Proliferative enteritis: endemic in Australian piggeries?

PMID- 8280032
TI  - Effect of lower body negative pressure on cerebral circulation.
AB  - This experiment was performed to study the effects of lower body negative
      pressure (LBNP) on cerebral circulation. Cerebral hemodynamics were monitored
      continuously and noninvasively in eight subjects at 30 mmHg of LBNP for 25
      minutes by following items: 1) the carotid Doppler flowmeter which measures the
      carotid blood flow, 2) the transcranial Doppler sonography which measures the
      flow velocity of the middle cerebral artery, 3) the near infrared
      spectrophotometer which measures the oxygenated and deoxygenated hemoglobin in
      the brain. The mean flow velocity of the middle cerebral artery and the blood
      flow of the common carotid artery significantly decreased during LBNP, even
      though the mean arterial blood pressure was well maintained. The oxygenated
      hemoglobin was significantly increased during LBNP, while the deoxygenated
      hemoglobin was not changed significantly. Our results suggest that exposure to
      moderate LBNP (30 mmHg) decreased the cerebral blood flow with the vasodilation
      on the arterial side of the brain.

PMID- 8280033
TI  - Lower extremity muscle thickness during 30-day 6 degrees head-down bed rest with
      isotonic and isokinetic exercise training.
AB  - Muscle thickness was measured in 19 bed-rested (BR) men (32-42 year) subjected to
      isotonic (ITE, cycle ergometer) and isokinetic (IKE, torque ergometer) lower
      extremity exercise training, and no exercise (NOE) training. Thickness was
      measured with ultrasonography in anterior thigh--rectus femoris (RF) and vastus
      intermedius (VI), and combined posterior leg--soleus, flexor hallucis longus, and
      tibialis posterior (S + FHL + TP)--muscles. Compared with ambulatory control
      values, thickness of the (S + FHL + TP) decreased by 9%-12% (p < 0.05) in all
      three test groups. The (RF) thickness was unchanged in the two exercise groups,
      but decreased by 10% (p < 0.05) in the NOE. The (VI) thickness was unchanged in
      the ITE group, but decreased by 12%-16% (p < 0.05) in the IKE and NOE groups.
      Thus, intensive, alternating, isotonic cycle ergometer exercise training is as
      effective as intensive, intermittent, isokinetic exercise training for
      maintaining thicknesses of rectus femoris and vastus intermedius anterior thigh
      muscles, but not posterior leg muscles, during prolonged BR deconditioning.

PMID- 8280031
TI  - Hormonal changes with lower body negative pressure on the 6th day in microgravity
      in one cosmonaut.
AB  - We measured volume regulating and stress hormones (AVP, aldosterone, ANP, c-GMP,
      angiotensin II, PRA, epinephrine, norepinephrine, ACTH, cortisol) in venous blood
      twice during a lower body negative pressure (LBNP) maneuver in one cosmonaut (31
      years, 75 kg, 180 cm) preflight (supine), inflight (6th d in orbit), and on the
      4th d (supine) after a 10-d flight. Antecubital blood was taken at the beginning
      (3 min: "a") and after ceasing (2 min: "b") 40 min LBNP (-15/-30/-35 mm Hg for
      15/15/10 min). At the beginning of LBNP, no big changes of resting hormone levels
      are to be expected. Comparison of "a" values: Inflight, there was a 4-5-fold
      increase in vasopressin and epinephrine, a slight increase in aldosterone, ANP,
      norepinephrine, cortisol and ACTH, and a decrease in PRA levels. Postflight,
      vasopressin was almost as much increased as inflight, and aldosterone and ANP
      levels were higher than pre- or inflight. PRA, epinephrine, norepinephrine, and
      cortisol were moderately increased, whereas ACTH and angiotensin II were
      diminished. Comparison of "b" to "a" values (2 min after LBNP to 3 min intra
      LBNP): Preflight, ANP, PRA, and epinephrine rose more than 100%. The inflight
      response was higher for aldosterone but lower for all other volume active
      hormones. Postflight, the increase in PRA was pronounced, whereas little change
      occurred in other hormones. Cortisol and ACTH fell similarly during LBNP under
      all conditions. In summary, the data provide evidence that not only the endocrine
      status but also the neuroendocrine responsiveness to stimulation; i.e., the
      hormone response during cardiovascular load, are altered by the stay in
      microgravity and readaptation to normal conditions.

PMID- 8280034
TI  - Increased glucose and 2-deoxy-D-glucose uptake in skeletal muscle of suspended
      rats.
AB  - The influence of 7-d of whole-body suspension (WBS) on insulin stimulated glucose
      and 2-deoxy-D-glucose uptake in resting skeletal muscle was examined.
      Differential hindlimb muscle atrophic effects characteristic of this model
      (soleus > gastrocnemius > EDL) were observed. WBS and control (C) rats underwent
      hindlimb perfusion following an overnight fast. The rate and magnitude of glucose
      uptake across the entire hindlimb and within six individual muscles were assessed
      following the addition of 150, or 1000 microU/ml insulin to a perfusate
      containing 10 mM glucose and 5 microCi of the non-metabolizable glucose analog 2
      deoxy-D-glucose (2-DG). The rate of uptake across the hindlimbs (A-V glucose
      difference x perfusate flow rate) was not different between C and WBS groups in
      the absence of exogenous insulin. At insulin concentrations of 150 and 1000
      microU/ml the hindlimb musculature of suspended rats exhibited uptakes
      significantly (p < 0.05) more rapid (increased initial slope of the uptake curve)
      and of greater magnitude (increased area under uptake curve) than that of C.
      Overall, no differences in basal (no exogenous insulin) 2-DG uptake were observed
      between C and WBS muscles. When 150 and 1000 microU/ml of insulin were added to
      the perfusate, individual muscles from suspended rats exhibited significantly (p
      < 0.05) greater accumulation of 2-DG than C. These in situ results derived from
      an intact hindlimb preparation are the first to correlate both total hindlimb and
      individual muscle glucose uptakes in suspended rats, and suggest an enhanced
      effect of insulin in skeletal muscle of suspended rats.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8280035
TI  - Unilateral frontal decortication changes cerebral blood flow distribution during
      hyperbaric oxygen exposure in rats.
AB  - Distribution of rCBF was measured with 10.7 +/- 0.5 microns differently
      radiolabelled microspheres (MS) during control at 1 bar air, and after 5 and 35
      min at 5 bar (0.5 MPa) 95% O2 on awake, habituated rats 10 d after right-sided
      frontal decortication. A decreased tolerance to hyperbaric O2 was found compared
      to normal rats of the same strain. The systolic arterial pressure increased
      during O2 exposure (11%, p < 0.05), the mean arterial pressure remained
      unchanged, but the cardiac output and heart rate fell by 29 and 14% (p < 0.01),
      respectively. The arterial acid-base balance remained normal during O2 exposure,
      although a small reduction of CO2 (24%) and HCO3 (11%) was observed (p < 0.01 and
      p < 0.05), possibly due to increased alveolar ventilation caused by an elevated
      respiratory rate of 24% (p < 0.05). The arterial O2 content at 5 bar increased by
      about 30% (p < 0.01). During control, blood flow in 16 regions of each hemisphere
      was found to be lower, more scattered, and differently distributed on the
      lesioned side. After 5 min at 5 bar, the blood flow fell in nearly all regions of
      the brain (up to 40%), similarly in the two brain halves. During the 35 min
      exposure, the blood flow increased, so that 60% of the examined areas on the
      lesioned side had blood flow levels of control or above, in contrast to the
      undisturbed side where blood flow remained below control values. The O2 supply to
      different regions varied similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280036
TI  - Epidemiology of decompression sickness under simulated space extravehicular
      activities.
AB  - Several ground-based trials were conducted by NASA at the Lyndon B. Johnson Space
      Center, Houston, TX, during 1982-90 to examine the risk of altitude decompression
      sickness (DCS) during space extravehicular activities. There were 22 different
      pressure profiles involving single and staged decompression procedures, each
      lasting from 180 to 360 min at the final altitude. A total of 164 healthy
      subjects participated in 426 exposures to altitude. Symptoms of DCS occurred in
      17% (74/426) and circulating microbubbles by precordial Doppler ultrasound were
      detected in 42% (179/426) of all exposures. About 27% (20/74) of exposures with
      symptoms resulted in test abort, and one-third of all test aborts required
      treatment in the hyperbaric chamber. There was about 3.20 times (95% Confidence
      Interval [95% CI] = 1.56-6.66) higher risk of symptoms in the presence of Doppler
      detectable microbubbles. Examination of individual risk factors showed that there
      was about 4.3 times (95% CI = 1.62-11.50) higher risk of symptoms with increasing
      number of exposures. These findings emphasize the importance of evaluating risk
      factors from ground-based trials for application in operational decision-making
      and treatment strategies.

PMID- 8280037
TI  - Delayed onset arterial gas embolism.
AB  - Numerous civilian and military personnel are involved in SCUBA diving activities.
      In this day of rapid air travel it is important that all physicians, not just
      those living near the coast or dive centers, be familiar with the basics of
      diagnosing and treating diving-related injuries. One of the more serious
      complications of dysbarism is Arterial Gas Embolism (AGE). This case history
      involves an atypical presentation of delayed onset AGE in a military diver
      trainee, and its treatment. This article then reviews the incidence, etiology,
      pathophysiology, "classic" presentation and current treatment of this disease.
      Systemic pathophysiology secondary to the effects of intravascular air of AGE is
      also discussed.

PMID- 8280038
TI  - Aircrew soft contact lens wear: a survey of USAF eyecare professionals.
AB  - The USAF, when it approved soft contact lens (SCL) wear for aircrew in June 1989,
      chose a conservative approach that authorizes only daily-wear of extended-wear
      SCL's. The aircrew SCL program has been perceived as a success, and follow-up
      data are no longer being collected. A survey was sent to all USAF eyecare
      professionals to assess the types and extent of SCL-related ocular pathology, the
      magnitude of environmental SCL problems in the cockpit, and the brands of SCL's
      that are being fitted. Only two instances of ulcerative keratitis were reported.
      The most severe inflight problem reported was the dry cockpit environment. CSI-T
      (Pilkington Barnes-Hind) was the most frequently used spherical lens and the
      Hydrasoft Toric XW (CoastVision) was the most used toric lens. The USAF aircrew
      SCL program appears to be progressing successfully. However, the Ophthalmology
      Branch at Armstrong Laboratory will continue to monitor the program for serious
      medical complications.

PMID- 8280039
TI  - Prevention of decompression sickness in current and future fighter aircraft.
AB  - United States Air Force oxygen regulators set to "NORMAL OXYGEN" deliver up to
      60% nitrogen to the pilot at cockpit altitudes of 15,000 to 20,000 ft (4573-6096
      m). Research chamber exposure to these altitudes while breathing 50% nitrogen has
      resulted in high grades of venous gas emboli. Expansion of existing gas emboli
      following an unplanned decompression to ambient aircraft altitude (e.g., loss of
      canopy) could result in rapid development of decompression sickness (DCS)
      symptoms. To reduce this potential problem, regulators in current fighters should
      be set to "100% OXYGEN" until descent from cruise to increase denitrogenation.
      The United States' Advanced Tactical Fighter and the European Fighter Aircraft
      may be designed to cruise above 50,000 ft (15,240 m), where cockpit altitudes
      exceed 20,000 ft with a 5-psi differential (psid) cockpit pressurization
      schedule. Increasing cockpit differential pressure to 7 psid while breathing 100%
      oxygen would greatly reduce the chance of significant emboli formation and the
      potential for DCS, but would slightly elevate the risks associated with pulmonary
      overpressure during rapid decompression.

PMID- 8280040
TI  - A case of chronic depression.
AB  - The authors describe a case of chronic depression in a designated Naval Aviator
      with a concomitant history of hypothyroidism. The differential diagnosis of
      dysthymia is discussed and the associated therapeutic alternatives are reviewed.
      The case demonstrates the importance of comprehensive physical and psychiatric
      evaluation of those patients with complex or atypical presentations. Issues
      pertaining to the aeromedical disposition of such patients are discussed, with
      emphasis on the role of the flight surgeon.

PMID- 8280041
TI  - Cases from the aerospace medicine residents' teaching file. Case #55. Symmetrical
      peripheral edema in a 33-year-old Army aviator.
AB  - Initial presentation, evaluation, differential diagnosis, and aeromedical
      disposition of a 33-year-old aviator with tropical sprue is discussed. This
      unusual case was unique in that the applicable flight regulations do not address
      tropical sprue.

PMID- 8280042
TI  - Aviation safety and asymptomatic HIV-1 infection.

PMID- 8280044
TI  - Small N experiments.

PMID- 8280043
TI  - Acute diarrhea and oral rehydration solutions.

PMID- 8280045
TI  - Overhead and forward reach capability during exposure to +1 to +6 Gx loads.
AB  - The lack of reach performance data obtained under space-flight conditions has led
      to questions regarding the operational impact of higher G loads on crew
      performance. This investigation studied the effect of increasing G loads on reach
      capability. Ten subjects were exposed in a stepwise fashion to increasing
      accelerations resulting in G loads of from +1 to +6 Gx in the Brooks AFB
      centrifuge. Four subjects wore the pre-Challenger Launch Entry Helmet (LEH)
      ensemble and six the current Launch Entry Suit (LES). The subjects performed
      standardized reach sweeps at each G level. These sweeps were recorded on
      videotape and subsequently analyzed using a 3-dimensional motion analysis system.
      Significant differences in forward and overhead reach were determined using the
      General Linear Models (GLM) procedure of the Statistical Analysis System (SAS)
      program. The results from this study suggest that purposeful movement can be
      realistically performed in the LEH at the 5 G level and in the LES up to the 4 G
      level.

PMID- 8280046
TI  - Mission challenge, mental workload and performance in military aviation.
AB  - In modern military aircraft, complexity of information combined with time stress
      creates difficulties for the pilot under combat conditions. The first step to
      mitigate this problem is to measure mental workload. Several methods for doing so
      have been proposed. In this paper we develop an analysis of mental workload as
      distinguished from its prior flight mission parameters (risk, challenge) and
      subsequent effects (mission performance). A model is developed on the basis of
      extensive mission data, both ground attack and fighter missions, which exhibits a
      dual coping process as a response to challenge and risk: emotion coping, leading
      to tension and decreased performance, and problem solving, leading to increased
      mental energy and improved performance. The model implies a selection of optimal
      measures for constructing an index of mental workload which is demonstrated to
      yield a sensitive measure of the pilot's changing mental status over the course
      of a period of training.

PMID- 8280047
TI  - Air quality assessments for two recent Space Shuttle flights.
AB  - Degradation of air quality in the Space Shuttle environment through chemical
      contamination and high solid-particulate levels may affect crew performance and
      health. A comprehensive study of the Shuttle atmosphere was undertaken during the
      STS-40 (Spacelab Space Life Sciences 1) and STS-42 (Spacelab International
      Microgravity Laboratory 1) missions to determine the effectiveness of contaminant
      control procedures by measuring concentrations of volatile organic compounds and
      analyzing particulate matter trapped on air filters. Analysis of volatile
      contaminants showed that the air was toxicologically safe to breathe during both
      missions with the exception of one period during STS-40 when the Orbiter
      Refrigerator/Freezer was releasing noxious gases into the middeck. Chemical
      analyses of selected particles collected on air filters facilitated their
      positive identification. Trace amounts of rat hair and food particles were found
      in the STS-40 Spacelab filters; a trace amount of soilless plant-growth media was
      detected in the STS-42 Spacelab filter. The low levels of particles released from
      these Spacelab experiments indicate that containment measures were effective.

PMID- 8280049
TI  - Platelet adhesion to collagen via the alpha 2 beta 1 integrin under arterial flow
      conditions causes rapid tyrosine phosphorylation of pp125FAK.
AB  - Adhesion of human platelets to collagen under arterial flow conditions mediated
      by the alpha 2 beta 1 integrin increased tyrosine phosphorylation of several
      proteins, one of which was the focal adhesion tyrosine kinase, pp125FAK. Tyrosine
      phosphorylation of pp125FAK did not occur in non-adherent flowing platelets or in
      platelets attached to poly(L-lysine). Neither adhesion nor tyrosine
      phosphorylation was affected by pretreatment of platelets with GRGDSP peptide or
      by anti-alpha IIb beta 3 monoclonal antibody P2. Adherent platelets retained
      their discoid shape, suggesting that induction of pp125FAK precedes platelet
      spreading. The tyrosine kinase inhibitor erbstatin decreased tyrosine
      phosphorylation in non-stimulated platelets and blocked platelet adhesion. These
      results suggest that pp125FAK plays an important role in platelet adhesion to
      collagen via the alpha 2 beta 1 integrin.

PMID- 8280050
TI  - The relative rate of aequorin regeneration from apoaequorin and coelenterazine
      analogues.
AB  - The regeneration of an active semi-synthetic aequorin, from apoaequorin produced
      in cells and a coelenterazine analogue, is a key step in measuring Ca2+ in the
      cells. The relative rates of the regeneration of semi-synthetic aequorins from
      apoaequorin and 28 synthetic coelenterazine analogues were compared. The results
      indicated that the rate is strongly influenced by the analogues used. The
      regeneration of ordinary aequorin with normal coelenterazine was relatively fast
      (50% regeneration in 22 min), whereas the rates of regenerating semi-synthetic
      aequorins with coelenterazine analogues varied widely, and all were slower than
      that of regenerating ordinary aequorin, except for e-type coelenterazines
      (containing an extra ethano group). The regeneration with e-type coelenterazines
      was significantly faster, indicating the possible superiority of e-type analogues
      in the intracellular regeneration of aequorin, especially when an increased
      sensitivity to Ca2+ is needed.

PMID- 8280051
TI  - Immobilized pH gradient focusing of alkaline proteins: analysis of the isoform
      composition of purified human non-secretory ribonucleases from kidney, liver and
      spleen.
AB  - Previous studies on the isoform composition of human ribonucleases (RNAases) have
      resulted in confusing and inconsistent results, presumably due to methodological
      problems in electrofocusing of alkaline proteins. In the present study,
      immobilized pH gradient (IPG) carrier ampholyte (CA) isoelectric focusing (IEF)
      and conventional CA-IEF have been evaluated for the analysis of the isoforms of
      human non-secretory RNAases purified from kidney, liver and spleen. CA-IEF proved
      unsuitable since the alkaline RNAase isoforms migrated into the cathode. IPG-CA
      IEF, however, resolved the RNAase isoforms and marker proteins in the basic
      region of the gel matrix. The three RNAases had comparable isoform profiles, each
      with two protein bands with approximate pI values of 10.3 and 10.4. Western
      blotting showed that the two protein bands of each RNAase were immunoreactive
      (with polyclonal antibodies that recognize RNAase), indicating that the protein
      bands are RNAase isoforms. The present results provide reliable pI data on human
      RNAase isoforms and suggest that IPG-CA-IEF should be a suitable technique for
      analysing the isoforms of other alkaline proteins.

PMID- 8280052
TI  - p40phox, a third cytosolic component of the activation complex of the NADPH
      oxidase to contain src homology 3 domains.
AB  - The NADPH oxidase generates superoxide in phagocytic cells. It is important for
      immunity and its deficiency leads to chronic granulomatous disease (CGD). It
      consists of a membrane-bound flavocytochrome b that lies dormant until activated
      by the translocation to the plasma membrane of cytosolic proteins, p47phox (phox
      for phagocyte oxidase), p67phox and p21rac, a small GTP-binding protein. We show
      here that a novel component, p40phox, forms an activation complex with p47phox
      and p67phox with which it translocates to the membrane to associate with the
      flavocytochrome b. cDNA cloning and amino acid analysis revealed that p40phox has
      an src homology 3 (SH3) domain and a large region of sequence similarity with the
      N-terminus of p47phox. The primary association of p40phox appears to be with
      p67phox, and it is present in reduced amounts in patients with CGD lacking
      p67phox.

PMID- 8280053
TI  - Effect of selective thiol-group derivatization on enzyme kinetics of (R)-3
      hydroxybutyrate dehydrogenase.
AB  - (R)-3-Hydroxybutyrate dehydrogenase (BDH) is a phosphatidylcholine-requiring
      tetrameric enzyme with two thiol groups (SH-1 and SH-2) per protomer. By first
      protecting the more rapidly reacting thiol group (SH-1) with diamide [1,1'-azobis
      (NN'-dimethylformamide), DM] to form DM(SH-1)BDH, SH-2 can be selectively
      derivatized by reaction with maleimide reagents such as 4-maleimido-2,2,6,6
      tetramethyl-piperidine-N-oxyl (MSL), which gives DM(SH-1)MSL(SH-2)BDH. Reduction
      with dithiothreitol (DTT) regenerates SH-1, yielding MAL(SH-2)BDH (where MAL is
      the diamagnetic reduction product of MSL-BDH and DTT). The enzymic activity of
      DM(SH-1)BDH is decreased to approx. 4% relative to the native purified enzyme,
      and the apparent Km for substrate, KmBOH, is increased approx. 100-fold.
      Reduction of DM(SH-1)BDH with DTT regenerates SH-1 and restores normal enzymic
      function. Modification of SH-2 with piperidinylmaleimide [MAL(SH-2)BDH]
      diminishes enzymic activity to approx. 35% of its original value, but has no
      significant effect on apparent KmBOH. The doubly derivatized enzyme, DM(SH
      1)MSL(SH-2)BDH, has lower enzymic activity [about half that for DM(SH-2)BDH] and
      a yet higher apparent KmBOH than DM(SH-1)BDH. Derivatization of SH-2 with
      different maleimide reagents results in diminished activity approximately
      proportional to the size of the maleimide substituent, suggesting that this
      inhibition is steric. Whereas modification of SH-1 results in marked changes in
      kinetic parameters (increased apparent Km and reduced apparent Vmax),
      derivatization of SH-2 has a lesser effect on enzymic function. Thus SH-1 is
      postulated to be closer to the active centre than is SH-2, although neither is
      involved in catalysis, since: (1) the activity of the derivatized enzyme is not
      abolished; and (2) activity can be enhanced by increasing substrate (and
      cofactor) concentrations.

PMID- 8280054
TI  - Primary structure and characterization of an androgen-stimulated autoantigen
      purified from mouse seminal-vesicle secretion.
AB  - A protein extract of mouse seminal-vesicle secretion was used to immunize mature
      mice (Balb/c) of both sexes. Results of Western-blot analyses for these secretory
      proteins indicated that only one minor protein component could be recognized by
      the autoantisera prepared from either autoimmunization of male mice or
      isoimmunization of female mice. The autoantigen was purified from seminal-vesicle
      secretion. The purified autoantigen retained the ability to induce autoantibody
      formation. The autoantigen has glycoprotein characteristics: the majority of the
      carbohydrate is N-linked and the remainder is O-linked. Rabbit antibodies to the
      autoantigen were used to isolate the corresponding cDNA from a mouse seminal
      vesicle cDNA library. The primary structure deduced from the cDNA sequence was
      confirmed by direct amino acid sequence determination. The results indicate that
      the core protein consists of 131 amino acid residues. Analysis of the primary
      structure indicates that the autoantigen has two potential acceptor sites for the
      N-linked carbohydrate at Asn-12 and Asn-122, three potential phosphorylation
      sites for casein kinase II at Thr-55, Ser-68 and Thr-76, and three potential
      phosphorylation sites for protein kinase C at Thr-28, Thr-40 and Thr-124. The
      core protein and the carbohydrate portion together have a molecular mass of 19
      kDa. Results from Western- and Northern-blot analyses for various tissues
      indicate that the seminal vesicle is the sole organ producing this autoantigen.
      Expression of this autoantigen gene was stimulated by testosterone.

PMID- 8280055
TI  - Tryptophan fluorescence study on the interaction of pulmonary surfactant protein
      A with phospholipid vesicles.
AB  - The fluorescence characteristics of surfactant protein A (SP-A) from porcine and
      human bronchoalveolar lavage were determined in the presence and absence of
      lipids. After excitation at either 275 or 295 nm, the fluorescence emission
      spectrum of both proteins was characterized by two maxima at about 326 and 337
      nm, indicating heterogeneity in the emission of the two tryptophan residues of SP
      A, and also revealing a partially buried character for these fluorophores.
      Interaction of both human and porcine SP-A with various phospholipid vesicles
      resulted in an increase in the fluorescence emission of tryptophan without any
      shift in the emission wavelength maxima. This change in intrinsic fluorescence
      was found to be more pronounced in the presence of dipalmitoyl
      phosphatidylcholine (DPPC) than with dipalmitoyl phosphatidylglycerol (DPPG),
      DPPC/DPPG (7:3, w/w) and 1-palmitoyl-sn-glycerol-3-phosphocholine (LPC).
      Intrinsic fluorescence of SP-A was almost completely unaffected in the presence
      of egg phosphatidylcholine (egg-PC). In addition, we demonstrated a shielding of
      the tryptophan fluorescence from quenching by acrylamide on interaction of
      porcine SP-A with DPPC, DPPG or LPC. This shielding was most pronounced in the
      presence of DPPC. In the case of human SP-A, shielding was only observed on
      interaction with DPPC. From the intrinsic fluorescence measurements as well as
      from the quenching experiments, we concluded that the interaction of some
      phospholipid vesicles with SP-A produces a conformational change on the protein
      molecule and that the interaction of SP-A with DPPC is stronger than with other
      phospholipids. This interaction appeared to be independent of Ca2+ ions.
      Physiological ionic strength was found to be required for the interaction of SP-A
      with negatively charged vesicles of either DPPG or DPPC/DPPG (7:3, w/w).
      Intrinsic fluorescence of SP-A was sensitive to the physical state of the DPPC
      vesicles. The increase in intrinsic fluorescence of SP-A in the presence of DPPC
      vesicles was much stronger when the vesicles were in the gel state than when they
      were in the liquid-crystalline state. The effect produced by SP-A on the lipid
      vesicles was also dependent on temperature. The aggregation of DPPC, DPPC/DPPG
      (7:3, w/w) or dimyristoyl phosphatidylglycerol (DMPG) was many times higher below
      the phase-transition temperature of the corresponding phospholipids. These
      results strongly indicate that the interaction of SP-A with phospholipid vesicles
      requires the lipids to be in the gel phase.

PMID- 8280056
TI  - Production of rat soluble and membrane-bound catechol O-methyltransferase forms
      from bifunctional mRNAs.
AB  - In the rat, the catechol O-methyltransferase (COMT) gene has been found to
      contain two promoters, P1 and P2. This organization enables the gene to produce a
      soluble (S-COMT) and a membrane-associated (MB-COMT) protein by using two in
      frame ATG initiation codons (S- and MB-ATG). The P1 promoter expresses a 1.6 kb
      transcript (S-mRNA) which codes for the S-COMT polypeptide only. Here we
      demonstrate that the P2 promoter controls the expression of alternatively spliced
      1.9 kb transcripts (MB-mRNA) which differ by a 27-nucleotide region immediately
      upstream of the MB-AUG codon. The presence of the 27-base sequence alters the
      nucleotide at position -3 from G to C, thereby changing the translation
      initiation context of the MB-AUG codon. Expression experiments in COS-7 cells
      using full-length COMT cDNAs showed that this alteration affected the initiation
      of the translation of the MB-AUG and consequently changed the relative amounts of
      MB- and S-COMT polypeptides produced. No proteolytic cleavage of the MB-COMT form
      to S-COMT was detected in in vitro or in vivo pulse-chase experiments. We
      conclude that the bifunctional 1.9 kb mRNAs are able to produce both S-COMT and
      MB-COMT polypeptide by the leaky scanning mechanism of translation initiation.

PMID- 8280048
TI  - Negative regulation of transcription in eukaryotes.

PMID- 8280057
TI  - Reaction of proteasomes with peptidylchloromethanes and peptidyldiazomethanes.
AB  - The multicatalytic endopeptidase complex (proteasome) has multiple distinct
      peptidase activities. These activities have often been referred to as
      'chymotrypsin-like', 'trypsin-like' and 'peptidylglutamyl-peptide hydrolase'
      activities according to the type of residue in the P1 position, although it is
      now clear that mammalian proteasomes have at least five distinct catalytic sites.
      In the present study, potential affinity-labelling reagents
      (peptidylchloromethanes, peptidyldiazomethanes, a peptidylfluoromethane and
      peptidylsulphonium salts) containing hydrophobic, basic or acidic amino acid
      residues in the P1 position have been tested for inhibition of the different
      activities of the rat liver proteinase complex. The results show that individual
      peptidase activities of proteasomes can be inhibited by a variety of
      peptidylchloromethanes and peptidyldiazomethanes. Although the rate of
      inactivation of proteasomes by even the most effective peptidylchloromethanes and
      peptidyldiazomethanes are often quite slow (k(obs)/[I] in the range 0.1-10 M-1 x
      s-1) compared with the reaction of similar compounds with some other proteinases,
      the results provide useful information concerning the specificity of the distinct
      catalytic centres of proteasomes, and some selective affinity-labelling reagents
      have been identified. Tyr-Gly-Arg-chloromethane was found to be a useful
      inhibitor of trypsin-like activity. Inhibition of the other peptidase activities
      was often incomplete, even after repeated addition of inhibitor, and it proved to
      be difficult to predict the effect of different reagents. For example, Cbz-Tyr
      Ala-Glu-chloromethane was found to inhibit 'chymotrypsin-like' activity (assayed
      with Ala-Ala-Phe-7-amino-4-methylcoumarin or succinyl-Leu-Leu-Val-Tyr-7-amino-4
      methylcoumarin), while the best inhibitors of 'peptidylglutamyl-peptide
      hydrolase' activities (assayed with benzyloxycarbonyl-Leu-Leu-Glu beta
      naphthylamide) were peptidyldiazomethanes containing hydrophobic amino acid
      residues. These results suggest that the original nomenclature of proteasome
      activities is misleading, because the residue in the P1 position is not the only
      determinant of specificity.

PMID- 8280058
TI  - Human small intestinal angiotensin-converting enzyme: intracellular transport,
      secretion and glycosylation.
AB  - Human intestinal angiotensin-converting enzyme (ACE) exists in the brush-border
      membrane as a monomeric protein of apparent molecular mass 184 kDa. It is
      associated with the membrane via a hydrophobic segment and has a transmembrane
      orientation [Naim (1992) Biochem. J. 286, 451-457]. In addition to the membrane
      bound form (ACEm), hydrophilic forms of ACE (ACEsec) can be identified in
      biosynthetically labelled intestinal cells. Thus the culture medium of
      biosynthetically labelled human biopsy samples contains an ACE molecule which has
      an apparent molecular mass similar to that of its membrane-bound counterpart. The
      secreted ACEsec forms follow a precursor/product relationship with the mature ACE
      molecule. The effect of the monomeric structure of ACE in its intracellular
      transport and secretion was investigated by pulse-chase experiments on human
      biopsy samples labelled with [35S]methionine. The results reveal 2-3-fold slower
      transport of ACE from the endoplasmic reticulum (ER) to the Golgi as compared
      with the homodimeric proteins dipeptidylpeptidase IV and aminopeptidase N.
      Further, the transport kinetics of ACE are comparable with those of human sucrase
      isomaltase and human maltase-glucoamylase, two brush-border disaccharidases that
      do not form homodimers in the ER of human small-intestinal cells. These findings
      strongly suggest that homodimerization of brush-border proteins may influence the
      rate of transport of these proteins from the ER to the Golgi. The effect of
      glycosylation on the transport and secretion of ACE was investigated by utilizing
      several inhibitors of glycan processing. Here, secretion of ACE molecules
      continued to take place, albeit to a considerably lesser extent. In fact, approx.
      2-fold less ACE molecules were secreted in the presence of inhibitors of ER
      glucosidases I and II and cis-Golgi mannosidase-I, suggesting that carbohydrate
      processing is important in the attainment of a transport-competent conformation.

PMID- 8280059
TI  - Two distinct secretory ribonucleases from human cerebrum: purification,
      characterization and relationships to other ribonucleases.
AB  - Two RNAases from human cerebrum were purified to an electrophoretically
      homogeneous state and their molecular masses were 22.0 kDa (tentatively called
      RNAase HB-1) and 19.0 kDa (RNAase HB-2). Analyses of the amino acid compositions,
      N-terminal amino acid sequences and catalytic properties of these enzymes
      provided strong evidence that they were strictly related to the secretory (sec)
      RNAases, such as the pancreatic enzyme, very similar immunologically to urinary
      sec RNAase, but clearly distinguishable from urinary non-secretory (nonsec)
      RNAase. There were several differences between HB-1 and HB-2, namely their
      immunological reactivities with specific antibodies, heat-stabilities, attached
      carbohydrate moieties and molecular masses. In particular, HB-2 appeared to be
      nonglycosylated, in view of its lack of affinity for several conjugated lectins,
      the absence of hexosamine and no change in electrophoretic mobility before and
      after peptide:N-glycosidase F digestion, whereas HB-1 and human sec RNAases
      purified from kidney, pancreas and urine all appeared to be glycosylated, as they
      moved to the same position as HB-2 when electrophoresed after glycosidase
      digestion. An antibody against urinary sec RNAase inhibited 75% and 20% of the
      total activity of the crude cerebral extract against RNA at pH 8.0 and 6.0
      respectively, whereas an antibody against urinary nonsec RNAase had no such
      inhibitory effect. These findings suggest that yet another type(s) of cerebral
      RNAase, which is unable to cross-react immunologically with sec and nonsec
      RNAases, may exist. Two RNAases corresponding to HB-1 and HB-2 were identified in
      fresh cerebrospinal fluid.

PMID- 8280060
TI  - Topology of nucleotide-sugar:dolichyl phosphate glycosyltransferases involved in
      the dolichol pathway for protein glycosylation in native rat liver microsomes.
AB  - Activities of nucleotide-sugar:dolichyl phosphate glycosyltransferases (UDP-N
      acetylglucosamine:dolichyl phosphate N-acetylglucosaminyl 1-phosphotransferase,
      UDP-glucose:dolichyl phosphate glucosyltransferase and GDP-mannose:dolichyl
      phosphate mannosyltransferase) are not fully expressed in native microsomes and
      can be enhanced by pretreatment of the microsomes with detergent. To examine
      whether the latency of dolichyl phosphate glycosyltransferases in native
      microsomes reflects a lumenal orientation of the catalytic centre, we examined
      the effect of proteinase treatment of native microsomes on enzymic activity and
      investigated the relationship between enzymic activity and alteration of the
      permeability of the microsomal membrane barrier. The enzymic activities
      catalysing transfer of N-acetylglucosamine and glucose to lipid acceptors were
      proteinase-sensitive in native sealed microsomes. When various detergents were
      used to disrupt the membrane barrier, we found no relationship between activity
      of dolichyl phosphate glycosyltransferases and the latency of mannose-6
      phosphatase, which is a marker of the permeability properties of the microsomal
      membrane. Permeabilization of the endoplasmic reticulum membrane by the pore
      forming Staphylococcus aureus alpha-toxin did not affect glycosyltransferase
      activities. These results do not support the hypothesis that latency of the
      transferase activities is dependent on the permeability properties of the
      endoplasmic-reticulum membrane. Collectively our findings can best be explained
      by postulating that the active centres of the transferases are cytoplasmically
      oriented, while activation by detergent may be conformation-dependent.

PMID- 8280061
TI  - Effect of GTP on the dolichol pathway for protein glycosylation in rat liver
      microsomes.
AB  - Incubation of native rat liver microsomes with GTP resulted in enhanced
      incorporation of N-acetylglucosamine (GlcNAc) from UDP-GlcNAc into lipid
      acceptors. The stimulation of GlcNAc transfer by GTP was specific for GTP; ATP
      exerted no effect. The GTP effect was blocked by a non-hydrolysable GTP analogue
      guanosine 5'-[beta gamma-imido]triphosphate, indicating that GTP hydrolysis was
      crucial. Though dolichyl pyrophosphate NN'-diacetylchitobiose [Dol-PP-(GlcNAc)2]
      was the main radiolabelled product formed upon incubation of GTP-treated
      microsomes with UDP-GlcNAc, GTP selectively stimulated UDP-GlcNAc:dolichyl
      phosphate (Dol-P) N-acetylglucosaminyl 1-phosphotransferase (N-acetylglucosaminyl
      1-phosphotransferase). This conclusion was reached on the basis of experiments in
      which tunicamycin was used to selectively inhibit N-acetylglucosaminyl 1
      phosphotransferase. The enhanced transformation of Dol-P to dolichyl
      pyrophosphate N-acetylglucosamine (Dol-PP-GlcNAc) by GTP ultimately led to
      enhanced protein glycosylation. GTP-induced stimulation of GlcNAc incorporation
      in lipid and protein by GTP was observed also in microsomes fully permeabilized
      with Staph. aureus alpha-toxin. These findings refute the previous proposal
      [Godelaine, Beaufay, Wibo and Ravoet (1983) J. Cell Biol. 97, 340-350] that
      increased membrane permeability constitutes the mechanism whereby GTP activates
      the reactions of the dolichol pathway.

PMID- 8280062
TI  - Structure and contribution to the heparin cofactor II-mediated inhibition of
      thrombin of naturally oversulphated sequences of dermatan sulphate.
AB  - Dermatan sulphate (DS) obtained from bovine and pig mucosa and pig skin, and
      charge-enriched fractions of a selected DS preparation, were characterized in
      terms of charge density, M(r) and disaccharide composition of chondroitin ABC
      lyase digests, and by 13C-n.m.r. spectroscopy. Besides the major IdoA-GalNAc4SO3
      sequences, all DS preparations contain about 10% disulphated disaccharide
      sequences (mostly IdoA2SO3-GalNAc4SO3, with minor amounts of IdoA-GalNAc4,6SO3).
      DS fragments (prepared by radical-catalysed depolymerization of DS and retaining
      the internal structure of the parent polysaccharide) as well as Smith degraded
      fragments [SD-DS, obtained by controlled degradation of periodate-oxidized and
      borohydride-reduced DS (RO-DS)] with the general structure GalNAc4SO3(IdoA2SO3
      GalNAc4SO3)n-R (where R is the remnant of a glycol-split uronic acid, and n = 2-3
      and 3-4) were characterized by one- and two-dimensional 1H-n.m.r., 13C-n.m.r. and
      disaccharide composition analysis. In accordance with previous findings [Maimone
      and Tollefsen (1990) J. Biol. Chem. 265, 18263-18271], only fragments with n > or
      = 3 significantly enhance the heparin cofactor II-mediated inhibition of
      thrombin. In natural DS preparations and their fractions, this activity (as well
      as the antithrombotic activity in an animal model) appears to require IdoA2SO3
      containing sequences. The heparin cofactor II activity of DS, RO-DS and SD-DS
      fragments decreases with decreasing M(r). However, RO-DS fragments are more
      active than DS fragments of similar M(r), probably because of the extra
      flexibility endowed by glycol-split IdoA residues.

PMID- 8280063
TI  - N-glycosylation of human acetylcholinesterase: effects on activity, stability and
      biosynthesis.
AB  - The role of N-glycosylation in the function of human acetylcholinesterase
      (HuAChE) was examined by site-directed mutagenesis (Asn to Gln substitution) of
      the three potential N-glycosylation sites Asn-265, Asn-350 and Asn-464. Analysis
      of HuAChE mutants, defective in a single or multiple N-glycosylation sites, by
      expression in transiently or stably transfected human embryonal 293 kidney cells
      suggests the following. (a) All three AChE glycosylation signals are utilized,
      but not all the secreted molecules are fully glycosylated. (b) Glycosylation at
      all sites is important for effective biosynthesis and secretion; extracellular
      AChE levels in mutants defective in one, two or all three sites amounted to 20
      30%, 2-4% and about 0.5% of wild-type level respectively. (c) Some glycosylation
      mutants display impaired stability, as reflected by increased susceptibility to
      heat inactivation; substitution of Asn-464 has the most pronounced effect on
      thermostability. (d) Abrogation of N-glycosylation has no detectable effect on
      the enzyme activity of HuAChE; all glycosylation mutants, including the triple
      mutant, hydrolyse acetylthiocholine efficiently, displaying Km, kcat. and
      kcat./Km values similar to those of the wild-type enzyme. (e) In most mutants,
      inhibition profiles with edrophonium and bisquaternary ammonium ligands are
      identical with those of wild-type enzyme; the Asn-350 mutants, however, exhibit a
      slight decrease in their affinity towards these ligands. (f) Elimination of
      oligosaccharide side chains has no detectable effect on the surface-related
      'peripheral-site' functions; like the wild-type enzyme, all mutants were
      inhibited by propidium and by increased concentrations of acetylthiocholine.

PMID- 8280064
TI  - Analysis, by electrospray ionization mass spectrometry, of several forms of
      Clostridium pasteurianum rubredoxin.
AB  - Clostridium pasteurianum rubredoxin and its recombinant counterpart purified from
      Escherichia coli have been analysed by electrospray ionization m.s. (e.s.i.m.s.).
      Whereas the N-terminal methionine of the native protein is formylated, the
      recombinant one has a free N-terminal methionine. E. coli cells also produce a
      colourless protein from the cloned gene. This protein is absent from C.
      pasteurianum and was shown to be zinc-substituted rubredoxin. The molecular forms
      of rubredoxin detected by e.s.i.m.s. depended on the experimental conditions
      used. Significant conversion into apo-rubredoxin occurred when the proteins were
      ionized at acidic pH and detected in the positive-ion mode. This conversion was
      quantitative in the case of Zn-rubredoxin. In contrast, when the proteins were
      analysed at neutral pH in the negative-ion mode, only the holoproteins, i.e. the
      species initially present in the solutions, were detected in the spectra. The
      e.s.i.m.s. experimental conditions set up here may prove useful for the analysis
      of other acidic metalloproteins with weakly bound metals.

PMID- 8280065
TI  - Characterization of the solution properties and conformation of pneumolysin, the
      membrane-damaging toxin of Streptococcus pneumoniae.
AB  - Pneumolysin is a membrane-damaging toxin produced by Streptococcus pneumoniae. In
      order to understand fully the mode of action of this toxin, it is necessary to
      have an appreciation of the size, self-association behaviour and solution
      conformation of pneumolysin. A combination of analytical ultracentrifugation
      methodologies has shown that pneumolysin lacks self-association behaviour in
      solution and has provided a weight-average M(r) (M omega) of 52,000 +/- 2000,
      which was in agreement with that derived from the amino acid sequence. By
      determining a sedimentation coefficient (S20,w0) of 3.35 +/- 0.10 S, it was
      possible to suggest a model for the gross solution conformation of pneumolysin
      monomers. Spectroscopic methods provide additional secondary and tertiary
      structure information.

PMID- 8280066
TI  - Phorbol 12-myristate 13-acetate-stimulated phosphorylation of erythrocyte
      membrane skeletal proteins is blocked by calpain inhibitors: possible role of
      protein kinase M.
AB  - Human erythrocytes contain cytosolic protein kinase C (PKC) which, when activated
      by phorbol 12-myristate 13-acetate (PMA), induces the phosphorylation of the
      membrane skeletal proteins band 4.1, band 4.9 and adducin. We found that brief
      treatments of erythrocytes with PMA resulted in a decrease in cytosolic PKC
      content and in the transient appearance in the cytosol of a Ca(2+)- and
      phospholipid-independent 55 kDa fragment of PKC, called PKM. Prolonged treatment
      with PMA resulted in the complete and irreversible loss of erythrocyte PKC. To
      investigate the possible role of calpain in this process, the calpain inhibitors
      leupeptin and E-64 were sealed inside erythrocytes by reversible haemolysis. Both
      inhibitors prolonged the lifetime of PKC in PMA-treated cells, and leupeptin was
      shown to block the PMA-stimulated appearance of PKM in the cytosol.
      Significantly, leupeptin also completely blocked PMA-stimulated phosphorylation
      of membrane and cytosolic substrates. This effect was mimicked by other calpain
      inhibitors (MDL-28170 and calpain inhibitor I), but did not occur when other
      protease inhibitors such as phenylmethanesulphonyl fluoride, pepstatin A or
      chymostatin were used. In addition, the phosphorylation of exogenous histone
      sealed inside erythrocytes was also blocked by leupeptin. Immunoblotting showed
      that leupeptin did not prevent the PMA-induced translocation of PKC to the
      erythrocyte membrane. Thus inhibition of PKC phosphorylation of membrane skeletal
      proteins by calpain inhibitors was not due to inhibition of PKC translocation to
      the membrane. Our results suggest that PMA treatment of erythrocytes results in
      the translocation of PKC to the plasma membrane, followed by calpain-mediated
      cleavage of PKC to PKM. This cleavage, or some other leupeptin-inhibitable
      process, is a necessary step for the phosphorylation of membrane skeletal
      substrates, suggesting that the short-lived PKM may be responsible for membrane
      skeletal phosphorylation. Our results suggest a potential mechanism whereby
      erythrocyte PKC may be subject to continual down-regulation during the lifespan
      of the erythrocyte due to repeated activation events, possibly related to
      transient Ca2+ influx. Such down-regulation may play an important role in
      erythrocyte survival or pathophysiology.

PMID- 8280067
TI  - Cysteine residues are not essential for uncoupling protein function.
AB  - The uncoupling protein (UCP) of brown adipose tissue is a regulated proton
      carrier which allows uncoupling of mitochondrial respiration from ATP synthesis
      and, therefore, dissipation of metabolic energy as heat. In this article we
      demonstrate that, when UCP is expressed in Saccharomyces cerevisiae, it retains
      all its functional properties: proton and chloride transport, high-affinity
      binding of nucleotides and regulation of proton conductance by nucleotides and
      fatty acids. Site-directed mutagenesis demonstrates that sequential replacement
      by serine of cysteine residues in the UCP does not affect either its uncoupling
      activity or its regulation by nucleotides and fatty acids, and therefore
      establishes that none of the seven cysteine residues present in the wild-type UCP
      is critical for its activity. These data indicate that transport models involving
      essential thiol groups can be discounted and that chemical modification data
      require critical re-evaluation.

PMID- 8280068
TI  - Endogenous hydroperoxide formation, cell volume and cellular K+ balance in
      perfused rat liver.
AB  - Addition of benzylamine (0.5 mM) to isolated perfused rat liver led to a net
      release of K+ of 10.5 +/- 0.3 mumol/g, which was accompanied by a decrease in
      liver mass by 9.3 +/- 0.4% and a decrease of the intracellular water space by
      13.7 +/- 0.6%, suggestive of hepatocellular shrinkage. Benzylamine had no effect
      on the perfusion pressure, and there was a close relationship between benzylamine
      induced net K+ release and the accompanying decrease in liver mass. Benzylamine
      induced net K+ release was sensitive to inhibition of monoamine oxidase by
      pargyline and increased with benzylamine flux through monoamine oxidase,
      suggesting its dependence on intracellular H2O2 formation. In line with this,
      infusion of H2O2 (but not of benzaldehyde, the other product of benzylamine
      metabolism) stimulated net K+ release from the liver. However, at a given H2O2
      load K+ release was about 2-3-fold higher when H2O2 was generated intracellularly
      during the oxidation of benzylamine, as compared with exogenously delivered H2O2.
      Inhibition of catalase by 3-amino-1,2,4-triazole (0.2 mM) significantly increased
      the benzylamine-induced net K+ release as well as the benzylamine-induced release
      of GSSG into bile, but had no effect on benzylamine oxidation at monoamine
      oxidase. In the presence of Ba2+ (1 mM) or in Ca(2+)-free perfusions, the
      benzylamine-induced net K+ efflux was diminished by 60-70% or about 30%,
      respectively. This was not explained by the 20-30% decrease in flux through
      monoamine oxidase observed under these conditions. The results suggest that
      metabolic generation of H2O2 inside the liver leads to a net K+ efflux and
      subsequent hepatocellular shrinkage. Net K+ efflux under these conditions is
      enhanced when catalase is inhibited, suggesting that the rate of both
      intracellular H2O2 generation and degradation can modulate cellular K+ balance
      and cellular volume. The data support the idea that oxidative stress may affect
      hepatocellular functions also by lowering the hepatocellular hydration state.

PMID- 8280069
TI  - Iron (II) oxidation and early intermediates of iron-core formation in recombinant
      human H-chain ferritin.
AB  - The paper describes a study of Fe(II) oxidation and the formation of Fe(III)
      apoferritin complexes in recombinant human H-chain ferritin and its variants. The
      effects of site-directed changes in the conserved residues associated with a
      proposed ferroxidase centre have been investigated. A change in any of these
      residues is shown to reduce the rate of Fe(II) oxidation, confirming the
      importance of the ferroxidase centre in the catalysis of Fe(II) oxidation.
      Mossbauer and u.v.-difference spectroscopy show that in the wild-type protein
      Fe(II) oxidation gives rise to Fe(III) monomers, dimers and larger clusters. The
      formation of Fe(III) mu-oxo-bridged dimers occurs at the ferroxidase centre and
      is associated with fast oxidation: in three variants in which Fe(II) oxidation is
      especially slow, no Fe(III) dimers are seen. Within the time scale 0.5-20 min in
      wild-type human H-chain ferritin, dimer formation precedes that of the monomer
      and the progression dimer-->monomer-->cluster is observed, although not to
      completion. In a preliminary investigation of oxidation intermediates using a
      stopped-flow instrument, an Fe(III)-tyrosine complex reported by Waldo et al.
      (1993), is attributed to Tyr-34, a residue at the ferroxidase centre. The Fe(III)
      Tyr-34 complex, forms in 0.5 s and then decays, as dimer absorbance increases.
      The relationship between Fe(III)-tyrosinate and the formation of Fe(III) dimers
      is uncertain.

PMID- 8280070
TI  - Identification of a family of casein kinases in Paramecium: biochemical
      characterization and cellular localization.
AB  - Protein phosphorylation is believed to play a role in the regulation of ciliary
      motility in the protozoan Paramecium tetraurelia. Five protein kinases from
      Paramecium, activated by cyclic nucleotides or Ca2+, have been characterized
      previously. We report here the identification of a family of second-messenger
      independent casein kinases in Paramecium. Casein kinase activity was enriched in
      the soluble fraction of cilia, but there was also significant activity tightly
      associated with axonemes. Three ciliary casein kinase activities (soluble CKS1
      and CKS2, and axonemal CKA) were separated by chromatography and characterized.
      The native forms of all three were monomeric, with molecular masses of 28-45 kDa
      as judged by in-gel kinase assays and sizing by gel filtration. CKS2 was
      inhibited by heparin, but CKA was unaffected and CKS1 was stimulated. All three
      activities preferred acidic substrates such as casein and phosvitin, but they
      could be distinguished by their preference for other substrates. Antibodies
      against mammalian casein kinase I recognized CKS1 and CKS2 in immunoblots (43
      kDa), but did not stain CKA. The antibodies to casein kinase I were used to probe
      other cellular fractions. A 65 kDa antigen (particulate casein kinase, CKP) was
      enriched in particulate fractions of whole cells. This 65 kDa protein was found
      in isolated cell cortices, but was not present in the infraciliary lattice. This
      report represents the first biochemical identification of a casein kinase I
      family in protozoa.

PMID- 8280071
TI  - Effects of histone acetylation, ubiquitination and variants on nucleosome
      stability.
AB  - The properties of the nucleosomes of a salt-soluble, transcriptionally active
      gene-enriched fraction of chicken erythrocyte chromatin were evaluated by
      hydroxyapatite dissociation chromatography. We have demonstrated previously that
      the salt-soluble, transcriptionally active gene-enriched polynucleosomes are
      enriched in dynamically acetylated and ubiquitinated histones, and in an atypical
      U-shaped nucleosome that possessed about 20% less protein than a typical
      nucleosome. Further, newly synthesized histones H2A and H2B exchange
      preferentially with the nucleosomal histones H2A and H2B of this salt-soluble
      chromatin fraction. Analysis of the histones eluting from the hydroxyapatite
      bound chromatin demonstrated that hyperacetylated and ubiquitinated (u),
      including multi-ubiquitinated, H2A-H2B.1 dimers dissociated at lower
      concentrations of NaCl than unmodified dimers or dimers with histone variants
      H2A.Z and/or H2B.2. Cross-linking studies revealed that at least 50% of uH2B.1
      was paired with uH2A. uH2A-uH2B.1 dimers dissociated at lower NaCl concentrations
      than H2A-uH2B.1 dimers. Hyperacetylated histone (H3-H4)2 tetramers also eluted at
      lower concentrations of NaCl than unmodified tetramers. Our results support the
      idea that acetylation and ubiquitination of histones H2A and H2B.1 increase the
      lability of H2A-H2B.1 dimers in transcriptionally active nucleosomes. In
      contrast, our observations suggest that histone variants H2A.Z and H2B.2.
      stabilize the association of the H2A-H2B dimer in nucleosomes. The elevated
      lability of the H2A-H2B dimer may facilitate processes such as the exchange of
      these dimers with newly synthesized histones, the elongation process of
      transcription and transcription factor binding.

PMID- 8280072
TI  - Smooth-muscle mitogen-activated protein (MAP) kinase: purification and
      characterization, and the phosphorylation of caldesmon.
AB  - A single 42 kDa isoform of mitogen-activated protein (MAP) kinase is expressed in
      both embryonic and adult chicken gizzard. The gizzard MAP kinase, which cross
      reacts with anti-p44mpk antibody, has been purified from adult chicken gizzard
      and partially characterized. The purification protocol employs phenyl-Sepharose,
      polylysine-agarose, hydroxyapatite, Mono-Q and phenyl-Superose column
      chromatography. The purified enzyme phosphorylates myelin basic protein and
      gizzard high-molecular-mass (h-)caldesmon. Sea-star p44mpk and gizzard MAP kinase
      phosphorylate h-caldesmon at identical sites at the C-terminal domain, as
      revealed by tryptic-peptide mapping of the phosphorylated protein.
      Phosphorylation of h-caldesmon by gizzard MAP kinase abolishes its interaction
      with polymerized tubulin. The specific activity of the purified gizzard kinase
      toward myelin basic protein is similar to that of brain tau kinase, but is only a
      fraction of that of activated sea-star p44mpk. This suggests that, although a
      large amount of MAP kinase is present in the gizzard, only a small percentage of
      the enzyme is activated normally. Autophosphorylation of the gizzard kinase, at
      least in part on tyrosine residues, activates its kinase activity.

PMID- 8280073
TI  - Stereochemical course and structure of the products of the enzymic action of endo
      1,3-1,4-beta-D-glucan 4-glucanohydrolase from Bacillus licheniformis.
AB  - The stereochemical course of the reaction catalysed by endo-1,3-1,4-beta-D-glucan
      4-glucanohydrolase (EC 3.2.1.73) has been determined by 1H n.m.r. The enzyme
      catalysed hydrolysis of barley beta-glucan proceeds with overall retention of the
      anomeric configuration, indicating that the enzyme operates through a double
      displacement mechanism. The structures of the final oligosaccharide products, 3
      beta-O-cellobiosyl D-glucopyranoside and 3-beta-O-cellotriosyl D-glucopyranoside,
      have been completely assigned by 1H- and 13C-n.m.r. spectroscopy.

PMID- 8280074
TI  - A calmodulin-stimulated Ca2+ pump in plasma-membrane vesicles from Trypanosoma
      brucei; selective inhibition by pentamidine.
AB  - Despite previous reports [McLaughlin (1985) Mol. Biochem. Parasitol. 15, 189-201;
      Ghosh, Ray, Sarkar and Bhaduri (1990) J. Biol. Chem. 265, 11345-11351; Mazumder,
      Mukherjee, Ghosh, Ray and Bhaduri (1992) J. Biol. Chem. 267, 18440-18446] that
      the plasma membrane of different trypanosomatids only contains Ca(2+)-ATPase that
      does not show any demonstrable dependence on Mg2+, a high-affinity (Ca(2+)-Mg2+)
      ATPase was demonstrated in the plasma membrane of Trypanosoma brucei. The enzyme
      became saturated with micromolar amounts of Ca2+, reaching a Vmax. of 3.45 +/-
      0.66 nmol of ATP/min per mg of protein. The Km,app. for Ca2+ was 0.52 +/- 0.03
      microM. This was decreased to 0.23 +/- 0.05 microM, and the Vmax. was increased
      to 6.36 +/- 0.22 nmol of ATP/min per mg of protein (about 85%), when calmodulin
      was present. T. brucei plasma-membrane vesicles accumulated Ca2+ on addition of
      ATP only when Mg2+ was present, and released it to addition of the Ca2+ ionophore
      A23187. In addition, this Ca2+ transport was stimulated by calmodulin. Addition
      of NaCl to Ca(2+)-loaded T. brucei plasma-membrane vesicles did not result in
      Ca2+ release, thus suggesting the absence of a Na+/Ca2+ exchanger in these
      parasites. Therefore the (Ca(2+)-Mg2+)-ATPase would be the only mechanism so far
      described that is responsible for the long-term fine tuning of the intracellular
      Ca2+ concentration of these parasites. The trypanocidal drug pentamidine
      inhibited the T. brucei plasma-membrane (Ca(2+)-Mg2+)-ATPase and Ca2+ transport
      at concentrations that had no effect on the Ca(2+)-ATPase activity of human or
      pig erythrocytes. In this latter case, pentamidine behaved as a weak calmodulin
      antagonist, since it inhibited the stimulation of the erythrocyte Ca(2+)-ATPase
      by calmodulin.

PMID- 8280075
TI  - Acute effects of insulin-like growth factor I on inter-organ amino acid flux in
      protein-catabolic dogs.
AB  - The effects of acute administration of human recombinant insulin-like growth
      factor-I (rhIGF-I) on amino acid (AA) flux between hindlimbs, liver and gut were
      investigated in anaesthetized post-operative dogs. rhIGF-I produced about a 10
      fold increase in plasma IGF-I concentrations above baseline values (P < 0.001),
      increased the plasma levels of glucagon and adrenaline (P < 0.05), and evoked a
      fall in plasma glucose (-55 +/- 8%; (P < 0.001) and plasma total AA levels (-23
      +/- 8%; P < 0.05). AA flux in post-absorptive dogs under NaCl infusions was
      characterized by an efflux of AA from the hindlimbs (as a result of the protein
      catabolic situation), an equal AA balance across the gut and an AA uptake by the
      liver. The administration of rhIGF-I increased hepatic AA uptake in the NaCl
      group from 3.51 +/- 0.8 to 7.5 +/- 0.4 mumol/min per kg (P < 0.01) and in the AA
      infused group from 16.8 +/- 0.6 to 22.4 +/- 1.5 mumol/min per kg (P < 0.05), but
      did not influence the AA balance across hindlimbs and gut. Glucose infusions
      normalized the plasma concentrations of counter-regulatory hormones without
      influencing the inter-organ AA balances. We conclude that hypoaminoacidaemia
      caused by rhIGF-I infusions is the result of a stimulated AA uptake by the liver,
      but is unrelated to alterations of AA exchange across the hindlimbs.

PMID- 8280076
TI  - Catabolism of hirudin and thrombin-hirudin complexes in the rat.
AB  - The metabolic fate of the anticoagulant protein, hirudin, and its complex with
      thrombin are presently unknown. Therefore we have labelled hirudin and human
      thrombin-hirudin complex with the residualizing label dilactitol-125I-tyramine
      (*I-DLT) in order to identify their tissue sites of catabolism in the rat. The
      rapid plasma clearance of hirudin after intravenous injection was unaffected by
      *I-DLT labelling, and by 2 h 6% or less of the injected dose remained in the
      blood. The majority (80.3 +/- 4.0%, n = 2) of *I-DLT-hirudin radioactivity
      recovered in tissues was found in kidney, and kidney was also at least 150 times
      more active in taking up hirudin, on a weight basis, than any other tissue
      examined (liver, spleen, skin, muscle, intestine, fat, lung). *I-DLT-hirudin
      which bound to thrombin was isolated by chromatography on concanavalin A
      Sepharose; hirudin itself does not bind to concanavalin A. Radioactivity from
      thrombin-*I-DLT-hirudin was precipitable by anti-thrombin antibody and *I-DLT
      thrombin-hirudin was precipitable by anti-hirudin antibody. By 1 h after
      injection of labelled thrombin-hirudin complexes, the recoveries of radioactivity
      from hirudin and thrombin in liver were comparable (38.6 +/- 3.0 and 36.4 +/-
      4.1%, n = 3), whereas more radioactivity was recovered in kidney from hirudin
      than from thrombin (27.6 +/- 8.7 compared with 13.6 +/- 4.5%) and less was
      recovered in lung (0.4 +/- 0.2 compared with 17.7 +/- 2.9%). We conclude that
      hirudin is catabolized predominantly in kidney, whereas the thrombin-hirudin
      complex is catabolized by both liver and kidney.

PMID- 8280077
TI  - Characterization of two novel casein transcripts in rabbit mammary gland.
AB  - Two clones were isolated from a cDNA library corresponding to mRNAs which
      accumulate in mid-lactating (14 day) rabbit mammary gland and characterized by
      DNA sequencing. The two clones sequenced corresponded to two novel casein
      transcripts (pBRM5 and pBRM42). Relative mRNA abundances for the two clones were
      assessed by dot-blot analysis. Phylogenetic analysis and comparison of both pBRM5
      and pBRM42 with other members of the casein family revealed that the rabbit may
      be unique among mammals in expressing two alpha s2-casein genes. The presence of
      two alpha s2-casein genes in the rabbit may be the result of a relatively recent
      intergenic duplication event.

PMID- 8280078
TI  - Intracellular binding of glucokinase in hepatocytes and translocation by glucose,
      fructose and insulin.
AB  - The release of glucokinase from digitonin-permeabilized hepatocytes shows
      different characteristics with respect to ionic strength and [MgCl2] from the
      release of other cytoplasmic enzymes. Release of glucokinase is most rapid at low
      ionic strength (300 mM sucrose, 3 mM Hepes) and is inhibited by increasing
      concentration of KCl [concn. giving half-maximal inhibition (I50) 25 mM] or Mg2+
      (I50 0.5 mM). Release of phosphoglucoisomerase, phosphoglucomutase and glucose-6
      phosphate dehydrogenase is independent of ionic strength, but shows a small
      inhibition by MgCl2 (20%, versus > 80% for glucokinase). Lactate dehydrogenase
      release increases with increasing ionic strength [concn. giving half-maximal
      activation (A50) 10 mM KCl] or [MgCl2]. The rate and extent of glucokinase
      release during permeabilization in 300 mM sucrose, 5 mM MgCl2 or in medium with
      ionic composition resembling cytoplasm (150 mM K+, 50 mM Cl-, 1 mM Mg2+) depends
      on the substrate concentrations with which the hepatocytes have been
      preincubated. In hepatocytes pre-cultured with 5 mM glucose the release of
      glucokinase was much slower than that of other cytoplasmic enzymes measured.
      However, preincubation with glucose (10-30 mM) or fructose (50 microM-1 mM)
      markedly increased glucokinase release. This suggests that, in cells maintained
      in 5 mM glucose, glucokinase is present predominantly in a bound state and this
      binding is dependent on the presence of Mg2+. The enzyme can be released or
      translocated from its bound state by an increase in [glucose] (A50 15 mM) or by
      fructose (A50 50 microM). The effects of glucose and fructose were rapid (t1/2 5
      min) and reversible, and were potentiated by insulin and counteracted by
      glucagon. They were inhibited by cyanide, but not by cytochalasin D, phalloidin
      or colchicine. Mannose had a glucose-like effect (A50 approximately 15 mM),
      whereas galactose, 3-O-methyl-D-glucose and 2-deoxyglucose were ineffective. When
      hepatocytes were incubated with [2-3H, U-14C]glucose, the incorporation of 3H/14C
      label into glycogen correlated with the extent of glucokinase release. Since 2-3H
      is lost during conversion of glucose 6-phosphate into fructose 6-phosphate,
      substrate-induced translocation of glucokinase from a Mg(2+)-dependent binding
      site to an alternative site might favour the partitioning of glucose 6-phosphate
      towards glycogen, as opposed to phosphoglucoisomerase.

PMID- 8280079
TI  - Linkage of 17 beta-oestradiol dehydrogenase to actin by epsilon-(gamma-glutamyl)
      lysine in porcine endometrial cells.
AB  - We report on the discovery of interactions of porcine endometrial 17 beta
      oestradiol dehydrogenase with actin. The 17 beta-oestradiol dehydrogenase of
      porcine uteri is an essentially unidirectional enzyme compounded in specialized
      organelles. The enzyme activity in Brij 35 extracts of the particulate fraction
      of epithelial cells sedimenting between 1800 and 11,000 g(av). was collected by
      immunoadsorption and eluted at low pH. The eluate contained three proteins of 32,
      45 and 80 kDa as shown by SDS/PAGE and silver staining. They were identified by
      amino acid sequencing and immunotyping as oestradiol dehydrogenase (32 kDa),
      actin (45 kDa) and a covalent dehydrogenase-actin complex (80 kDa). Disulphides,
      aldimines, periodate-degradable bonds and hydrophobic interactions were excluded
      as linkages in the 80 kDa protein. The epsilon-(gamma-glutamyl)-lysine nature of
      the covalent cross-link was recognized by narrow-bore h.p.l.c. analysis of
      enzymic digests of electro-eluted 80 kDa material. An involvement of the actin
      anchor in positioning of the oestradiol dehydrogenase-containing organelles
      according to metabolic requirements is discussed.

PMID- 8280080
TI  - Regulation of matrix metalloproteinase expression in human vein and microvascular
      endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and
      phorbol ester.
AB  - Matrix metalloproteinases (MMPs) play a role in tissue remodelling and
      angiogenesis. We have investigated the expression and regulation of MMP-1
      (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin 1), MMP-7
      (matrilysin), MMP-9 (gelatinase B) and their inhibitors TIMP-1 and TIMP-2 in
      human umbilical vein, femoral vein and microvascular endothelial cells, and
      compared these data with those obtained with human synovial fibroblasts. Non
      stimulated vein endothelial cells expressed the mRNAs for MMP-1, MMP-2, TIMP-1
      and TIMP-2. MMP-3 mRNA and protein were undetectable or only weakly expressed,
      but could be stimulated by the inflammatory mediator tumour necrosis factor alpha
      (TNF alpha). The expression of MMP-3 and MMP-1 was further enhanced by phorbol 12
      myristate 13-acetate (PMA). Phorbol ester also induced TIMP-1 and MMP-9, the
      expression of the latter being further enhanced by TNF alpha or interleukin 1
      alpha (IL-1 alpha). Similar stimulatory effects were observed in microvascular
      endothelial cells. Hence the inflammatory mediator TNF alpha induces/enhances the
      production of several matrix metalloproteinases in human endothelial cells. On
      the other hand, MMP-2 and TIMP-2 were not affected or were affected in a variable
      way by TNF alpha and/or phorbol ester, suggesting a dissimilar regulation of
      these proteins. The cyclic AMP-enhancing agent forskolin affected the production
      of MMPs in a cell-type-specific way. In human vein endothelial cells it enhanced
      the PMA-mediated induction of MMP-9, whereas it suppressed this induction in
      human microvascular endothelial cells and in synovial fibroblasts. On the other
      hand, forskolin suppressed the PMA-mediated induction of MMP-1 and MMP-3 in
      synovial fibroblasts, while it enhanced or did not affect this induction in
      various types of human endothelial cells. These observations may have
      implications for future pharmacological intervention in angiogenesis.

PMID- 8280081
TI  - Mammalian inositol monophosphatase: the identification of residues important for
      the binding of Mg2+ and Li+ ions using fluorescence spectroscopy and site
      directed mutagenesis.
AB  - The fluorescence properties of residue Trp-219 in inositol monophosphatase are
      sensitive to the ionization of neighbouring groups. The pH-dependent changes in
      the fluorescence emission intensity and wavelength of maximum emission appear to
      arise as the result of two separate ionizations in the proximity of Trp-219,
      namely due to the ionization of His-217 and Cys-218. By studying the curve of
      fluorescence intensity against pH, given by the mutants Cys-218-->Ala or His-217-
      >Gln, the pK of His-217 was determined to be 7.54 and the pK of Cys-218 was
      estimated to be about 8.2. These mutants have altered kinetic parameters for
      catalytic Mg2+ ions and inhibitory Mg2+ and Li+ ions. The Cys-218-->Ala mutant
      enzyme is not subject to inhibition by concentrations of Mg2+ ions up to 400 mM
      and has a specific activity of 156% of the maximum obtainable activity of the
      native enzyme. The His-217-->Gln mutant enzyme shows reduced sensitivity to
      inhibition by Mg2+ and Li+ ions, and has a specific activity of 110% of that
      obtainable for the native enzyme.

PMID- 8280082
TI  - Calponin phosphorylation in vitro and in intact muscle.
AB  - Calponin, a thin-filament-associated protein implicated in the regulation of
      smooth-muscle contraction, is phosphorylated in vitro by protein kinase C and
      Ca2+/calmodulin-dependent protein kinase II [Winder and Walsh (1990) J. Biol.
      Chem. 265, 10148-10155] and dephosphorylated by a type 2A protein phosphatase
      [Winder, Pato and Walsh (1992) Biochem. J. 286, 197-203]. Unphosphorylated
      calponin binds to actin and inhibits the actin-activated myosin MgATPase; these
      properties are lost on phosphorylation. Although both serine and threonine
      residues in calponin are phosphorylated, the major site of phosphorylation by
      either kinase is Ser-175. Calponin also undergoes phosphorylation when bound to
      actin in synthetic thin filaments, in a reconstituted actomyosin system, in
      washed myofibrils and in tissue extracts; this results in dissociation of
      calponin from actin. Tryptic phosphopeptide mapping indicates that the same sites
      are phosphorylated in the bound as in the isolated protein. Toad stomach calponin
      exists in at least three isoforms which differ in charge but exhibit the same
      molecular mass on SDS/PAGE. In a toad stomach extract, all three isoforms are
      phosphorylated by protein kinase C or Ca2+/calmodulin-dependent protein kinase II
      as shown by two-dimensional gel electrophoresis (non-equilibrium pH-gradient gel
      electrophoresis and SDS/PAGE). Calponin phosphorylation also occurs in intact
      toad stomach smooth-muscle strips metabolically labelled with 32Pi and stimulated
      to contract with carbachol. These results support the hypothesis that calponin
      may be regulated in vivo by phosphorylation-dephosphorylation.

PMID- 8280083
TI  - Molecular cloning and tissue distribution of pig transforming growth factor
      alpha.
AB  - Transforming growth factor alpha (TGF alpha) was originally identified as a
      product of tumour tissues and transformed cells in culture. Although it is now
      clear that expression of this factor is not restricted to neoplastic cells, there
      remains relatively little information about the sites of expression of TGF alpha
      in normal tissues. Therefore, an amplified DNA fragment encoding the pig TGF
      alpha precursor was cloned by reverse transcription-PCR (RT-PCR) using RNA
      isolated from normal skin tissue as the template. Nucleotide sequence analysis
      predicts a 160-residue transmembrane polypeptide that differs from the rat, mouse
      and human TGF alpha precursors at 14, 15 and six sites respectively. The
      distribution of TGF alpha mRNA in a wide variety of pig tissues was analysed by
      RT-PCR, using oligonucleotide primers based on the pig TGF alpha cDNA sequence.
      TGF alpha transcripts were detected in RNA isolated from 17 of the 22 tissues
      analysed, including four previously unreported sites. Using an antibody raised
      against a synthetic TGF alpha peptide, we have immunolocalized TGF alpha protein
      to cells within the red pulp of the spleen and to the distal convoluted tubules
      of the kidney.

PMID- 8280084
TI  - The substrate specificity and structure of mitogen-activated protein (MAP) kinase
      activated protein kinase-2.
AB  - The substrate specificity of mitogen-activated protein (MAP) kinase-activated
      protein kinase-2 (MAPKAP kinase-2) was investigated by using synthetic peptides
      related to the N-terminus of glycogen synthase. The minimum sequence required for
      efficient phosphorylation was found to be Xaa-Xaa-Hyd-Xaa-Arg-Xaa-Xaa-Ser-Xaa
      Xaa, where Hyd is a bulky hydrophobic residue (Phe > Leu > Val >> Ala), and the
      peptide Lys-Lys-Phe-Asn-Arg-Thr-Leu-Ser-Val-Ala was phosphorylated with a Km of
      9.3 microM and Vmax. of 10 mumol/min per mg. MAPKAP kinase-1 (a homologue of
      ribosomal protein S6 kinase) also requires an arginine three residues N-terminal
      to the serine (position n-3), but not a hydrophobic residue at position n-5.
      Neither MAPKAP kinase-1 nor MAPKAP kinase-2 could tolerate a proline residue at
      position n + 1, indicating that their specificities do not overlap with that of
      MAP kinase. The specificity of calmodulin-dependent protein kinase-II resembled
      that of MAPKAP kinase-2, except that it could tolerate replacement of the
      arginine by a lysine and the phosphorylation-site serine by a threonine residue.
      Partial cDNAs encoding MAPKAP kinase-2 were isolated from rabbit and human
      skeletal muscle and human teratocarcinoma libraries, and Northern-blotting
      experiments revealed a single 3.3 kb mRNA transcript present at similar levels in
      six human tissues examined. The catalytic domain was most similar (35-40%
      identity) to calmodulin-dependent protein kinases II and IV, phosphorylase
      kinase, putative serine kinase H1 and the C-terminal domain of MAPKAP kinase-1,
      which form one branch of the protein kinase phylogenetic tree. The sequence N
      terminal to the catalytic domain is proline-rich and contains two putative SH3
      binding sites. The threonine residue phosphorylated by MAP kinase lies
      immediately C-terminal to the catalytic domain and is followed by a nuclear
      localization signal, Lys-Lys-(Xaa)10-Lys-Arg-Arg-Lys-Lys, near the C-terminus.

PMID- 8280085
TI  - Inhibition of protein synthesis in baby-hamster kidney cells blocks oxysterol
      mediated suppression of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA at a post
      transcriptional level.
AB  - The effects of the protein-synthesis inhibitor cycloheximide on 25
      hydroxycholesterol-mediated suppression of 3-hydroxy-3-methylglutaryl-CoA (HMG
      CoA) reductase mRNA levels were evaluated in the baby-hamster kidney cell line
      C100. Cells cultured in medium supplemented with delipidized fetal bovine serum
      and 25 microM lovastatin for 12-24 h had a 5-fold higher level of HMG-CoA
      reductase mRNA than cells grown in medium supplemented with non-delipidized fetal
      bovine serum (FBS). The higher level was due to increased transcription, as
      determined by run-on assays with isolated nuclei. Addition of 25
      hydroxycholesterol to lovastatin-treated cells lowered HMG-CoA reductase mRNA
      levels within 4 h of treatment to those of cells grown in FBS-supplemented
      medium. This decrease was due in part to a decrease in gene transcription.
      Cycloheximide added in conjunction with 25-hydroxycholesterol to lovastatin
      treated cells blocked the suppression of mRNA levels, but did not block oxysterol
      mediated suppression of transcription. In addition, cycloheximide added to cells
      grown in FBS-supplemented medium rapidly increased mRNA levels by 10-fold
      relative to untreated cells, with no comparable increase in transcription. No
      comparable increase in either the mRNA level or rate of transcription for beta
      actin was observed under such conditions. These results indicate that
      cycloheximide specifically stabilizes HMG-CoA reductase mRNA in the presence of
      oxysterols and suggests that continuous synthesis of a short lived protein
      regulator is required for oxysterol-mediated suppression of HMG-CoA reductase
      mRNA at a post-transcriptional level.

PMID- 8280086
TI  - Interaction of a 39 kDa protein with the low-density-lipoprotein-receptor-related
      protein (LRP) on rat hepatoma cells.
AB  - We have recently described a PAI-1-independent pathway of tissue-type plasminogen
      activator (t-PA) uptake and degradation on the rat MH1C1 hepatoma cell line.
      Further studies have implicated the low-density-lipoprotein-receptor-related
      protein (LRP) as the mediator of plasminogen-activator inhibitor type-1
      independent t-PA endocytosis. The LRP is a multi-functional receptor which is
      shared by a variety of ligands, including alpha 2-macroglobulin, apoprotein E
      enriched beta-very-low-density lipoprotein, t-PA and Pseudomonas exotoxin A. In
      each case, binding of ligand to this receptor can be inhibited by addition of the
      39 kDa LRP-receptor-associated protein. This protein, which co-purifies with the
      LRP receptor, is the focus of our present study. 125I-labelled 39 kDa protein
      binds specifically and with high affinity to a single kinetic binding species on
      the rat MH1C1 cell surface. Scatchard analysis reveals an equilibrium
      dissociation constant (Kd) of 3.3 +/- 0.9 (S.D.) nM, with 380,000 +/- 190,000
      (S.D.) binding sites per cell. Cross-linking studies indicate that the specific
      interaction between MH1C1 cells and the 39 kDa protein is mediated by an
      association with the LRP receptor. The 39 kDa protein strongly inhibits binding
      of 125I-t-PA, with an apparent Ki value of 0.5 nM. In addition, both unlabelled t
      PA and 125I-labelled 39 kDa protein can be co-bound and cross-linked to the same
      cell-associated LRP receptor. Endocytosis of cell-surface-associated 39 kDa
      protein was shown to be rapid, with internalized ligand subsequently degraded and
      released to the extracellular milieu. The rate of uptake and degradation of 125I
      labelled 39 kDa protein at 37 degrees C was determined to be 52 fmol/min per
      10(6) cells, and supports a model for active recycling of the LRP receptor.

PMID- 8280087
TI  - Molecular cloning of chicken aggrecan.

PMID- 8280089
TI  - Control analysis applied to the whole body: control by body organs over plasma
      concentrations and organ fluxes of substances in the blood.
AB  - Metabolic control analysis is adapted as a method for describing and analysing
      the control by organs in the body over the fluxes and concentrations of
      substances carried in the blood. This physiological control analysis can most
      usefully be applied to substances with fluxes into and out of organs that are
      uniquely dependent only on their plasma concentrations. The organ flux of a
      substance is defined as the steady-state net flux of a substance into a
      particular organ. The organ flux control coefficients quantify the extent to
      which a particular organ controls the flux of a substance into the same or
      another particular organ. Organ concentration control coefficients quantify the
      extent to which an organ controls the steady-state concentration of a substance
      in the blood. The control coefficients are additive and obey summation,
      connectivity and branching theorems. Thus the control coefficients can be
      determined experimentally by measuring the sensitivities (elasticities) of organ
      fluxes to the plasma concentration of the substance. As an example of the
      application of these concepts, the control of ketone-body metabolism in vivo is
      analysed using data from the literature.

PMID- 8280088
TI  - Effect on ligand binding of arginine mutations in recombinant rat liver fatty
      acid-binding protein.
AB  - Rat liver fatty acid-binding protein is able to accommodate a wide range of non
      polar anions in addition to long-chain fatty acids. The two arginine residues of
      rat liver fatty acid-binding protein, Arg122 and Arg126, have been mutated and
      the effect of mutation on ligand binding investigated. No significant decrease in
      affinity for the fluorescent fatty acid analogue, 11-(5
      dimethylaminonaphthalenesulphonyl amino)undecanoic acid, or oleate was observed.
      However, the apparent affinity for oleoyl-CoA was slightly increased with the
      mutations Ala122 and Gln122 such that oleoyl-CoA rather than oleate became the
      preferred ligand for these mutants. Small changes in protein stability were
      observed with the Arg122 mutations. The lack of notable ionic involvement of the
      conserved internal residue Arg122 in ligand binding is consistent with the
      hypothesis that the mode of ligand binding in liver fatty acid-binding protein is
      markedly different from that of other members of this lipid-binding protein
      family.

PMID- 8280090
TI  - Kinetics of the inhibition of human factor Xa by full-length and truncated
      recombinant tissue factor pathway inhibitor.
AB  - The inhibition equilibrium and kinetics of association and dissociation of the
      binding of three types of recombinant tissue factor pathway inhibitor (TFPI),
      namely full-length TFPI, C-terminal-truncated TFPI, and TFPI without the third
      Kunitz domain (TFPI1-161), to factor Xa have been measured. Formation and
      dissociation of the complexes were monitored by continuous measurement of the
      changes in the rate of hydrolysis of a peptidyl-p-nitroanilide substrate.
      Progress curves of product formation were fitted to a set of equations describing
      a one-step bimolecular inhibitory reaction in the presence of a competing
      substrate. For full-length TFPI the rate constants of association (kon) and
      dissociation (koff) were (5.1 +/- 0.7) x 10(6) M-1.s-1 and (2.6 +/- 0.9) x 10(
      4)s-1 respectively. Thus, although the inhibition constant (50 pM) is far below
      the plasma concentration (2.5 nM) of TFPI, the half-time for transition to
      equilibrium in plasma is rather long (66s). The truncated forms of TFPI differ in
      that they have a 4-fold lower kon value but a similar dissociation rate constant.
      Therefore the inhibition constant, Ki, is 4-fold higher (0.2 nM) and the half
      time to achieve equilibrium is prolonged to 250 s. The kon values of full-length
      and C-terminal-truncated TFPI, but not that of TFPI1-161, were found to decrease
      with increasing ionic strength.

PMID- 8280091
TI  - The peripheral subunit-binding domain of the dihydrolipoyl acetyltransferase
      component of the pyruvate dehydrogenase complex of Bacillus stearothermophilus:
      preparation and characterization of its binding to the dihydrolipoyl
      dehydrogenase component.
AB  - The peripheral subunit-binding domain of the dihydrolipoyl acetyltransferase
      polypeptide chain of the pyruvate dehydrogenase multienzyme complex of Bacillus
      stearothermophilus was released by limited proteolysis from a di-domain (lipoyl
      domain plus binding domain) encoded by a subgene over-expressed in Escherichia
      coli. The domain was characterized by N-terminal sequence analysis, electrospray
      m.s. and c.d. spectroscopy. It was found to be identical in all respects to a
      chemically synthesized peptide of the same sequence. The association of the di
      domain and binding domain (both natural and synthetic) with dihydrolipoyl
      dehydrogenase was analysed in detail and a tight binding was demonstrated. As
      judged by several different techniques, it was found that only one peripheral
      subunit-binding domain is bound to one dimer of dihydrolipoyl dehydrogenase,
      implying that the association is highly anti-cooperative.

PMID- 8280092
TI  - Asymmetrical distribution of L-isoaspartyl protein carboxyl methyltransferases in
      the plasma membranes of rat kidney cortex.
AB  - We have studied the distribution of membrane-associated L-isoaspartyl protein
      carboxyl methyltransferases (PCMTs) in plasma membranes purified from rat kidney
      cortex. Addition of CHAPS to brush-border membranes (BBM) and basolateral
      membranes (BLM) was required to measure optimal membrane-dependent methylation of
      ovalbumin and TS-isoD-YSKY, substrates of L-isoaspartyl PCMTs. Extraction of both
      membrane-associated enzymes was achieved with detergents, but not with high-salt
      solutions, suggesting a strong membrane attachment. However, upon phase
      partitioning using Triton X-114, both enzymes were predominantly associated with
      the detergent-poor phase, suggesting a relatively hydrophilic nature. The enzymes
      showed similar catalytic properties such as substrate recognition and affinity
      towards the methyl donor, S-adenosyl-L-methionine. The activity of the BBM
      enzyme, however, was about 2-fold higher than that of the BLM enzyme.
      Identification of the endogenous substrates located in the two plasma membranes
      by acidic gel electrophoresis in the presence of a cationic detergent revealed
      significant differences in the methyl-accepting proteins of both membranes. The
      BBM-methylated proteins had sizes of 35, 50 and 54 kDa, whereas the major BLM
      methylated substrates were of 97 and 100 kDa. The enzymes showed distinct
      behaviour on Mono Q anion-exchange chromatography. The BBM-associated PCMT did
      not bind to the column, being eluted in the flow-through, whereas the BLM enzyme
      bound to the column and was eluted at 0.15 M NaCl. Moreover, the two enzymes had
      different molecular masses under both denaturing and nondenaturing conditions,
      the BLM PCMT migrating at an apparent molecular mass of 29 kDa, compared with 27
      kDa for the BBM enzyme. Taken together, these results show the presence of two
      distinct L-isoaspartyl PCMTs in the plasma membranes of the kidney cortex.

PMID- 8280093
TI  - Cyclosporin A blocks 6-hydroxydopamine-induced efflux of Ca2+ from mitochondria
      without inactivating the mitochondrial inner-membrane pore.
AB  - Oxidative stress causes Ca(2+)-loaded mitochondria to release Ca2+. The mechanism
      of this efflux is unclear, but it appears to be associated with the opening of a
      pore in the mitochondrial inner membrane. Pore opening depolarizes the
      mitochondria, letting solutes enter the mitochondrial matrix, causing swelling.
      Cyclosporin A (CsA) prevents opening of this pore. The neurotoxin 6
      hydroxydopamine (6HD) autoxidizes, producing free radicals, which cause oxidative
      stress. In this paper it is shown that 6HD-induced efflux from Ca(2+)-loaded
      mitochondria was prevented by CsA. The 6HD-induced Ca2+ efflux was not
      accompanied by mitochondrial swelling, depolarization of the mitochondrial inner
      membrane or movement of radiolabelled sucrose into the mitochondrial matrix. In
      agreement with others [Schlegel, Schweizer and Richter (1992) Biochem. J. 285, 65
      69], these findings suggest that the mitochondrial pore remained closed during
      pro-oxidant-induced Ca2+ efflux. However, the implication that CsA blocks pro
      oxidant-induced Ca2+ efflux by some mechanism other than inactivating the
      mitochondrial pore, suggests that the interaction of CsA with mitochondria may be
      more complex than is currently supposed.

PMID- 8280094
TI  - Characterization of gamma- and delta-subunits of Ca2+/calmodulin-dependent
      protein kinase II in rat gastric mucosal cell populations.
AB  - We searched for the occurrence of a Ca2+/calmodulin-dependent protein kinase in
      rat gastric cell types as a likely member in the chain of gastrin- and muscarinic
      receptor-mediated signal transmission. A Ca(2+)- and calmodulin-dependent
      phosphorylation of major 50, 60 and 100 kDa substrates was observed in parietal
      cell cytosol and a major 60 and 61 kDa protein doublet was found to bind 125I
      calmodulin in 125I-calmodulin-gel overlays. A specific substrate of the
      multifunctional Ca2+/calmodulin-dependent protein kinase II, autocamtide II, was
      phosphorylated in a calmodulin-dependent manner. The specific inhibitor of this
      enzyme, KN-62, antagonized protein kinase activity. RNA extracted from gastric
      mucosal cells was shown to contain sequences of the gamma- and delta- but not
      alpha- and beta-subunits of the calmodulin-dependent kinase II, and mRNA of both
      subtypes was demonstrated in highly purified parietal, chief and mucous cells. A
      calmodulin-dependent kinase II composed of gamma- and delta-subunits is a likely
      mediator of Ca(2+)-dependent signal transmission in these populations of gastric
      cells.

PMID- 8280095
TI  - Lipopolysaccharide-induced change of ADP-ribosylation of a cytosolic protein in
      bone-marrow-derived macrophages.
AB  - Treatment of bone-marrow-derived macrophages with nanogram quantities of
      bacterial lipopolysaccharide (LPS) or with the synthetic bacterial lipopeptide
      analogue N-palmitoyl-(S)-[2,3-bis(palmitoyloxy)-(2RS)-propyl] (Pam3)Cys-Ala-Gly
      results in a change of ADP-ribosylation of a cytosolic 33 kDa protein. The
      immunostimulant-induced change is both dose- and time-dependent. It is not
      observed in macrophages from an LPS-unresponsive C3H/HeJ mouse strain upon
      treatment with LPS. Non-endotoxic LPS from Rhodopseudomonas pallustris, the
      inactive lipopeptide analogue Pam3CysOH, and LPS in the presence of polymyxin B
      fail to induce the change of ADP-ribosylation of the protein. These observations
      indicate that reversible protein modification by ADP-ribosylation might play a
      role in macrophage activation.

PMID- 8280096
TI  - Plasmin modulates the thrombin-evoked calcium response in C6 glioma cells.
AB  - Extracellular proteinases may be selectively targeted to cell surfaces by
      specific receptors or binding sites. In previous studies, we have characterized
      cellular binding sites for plasminogen and plasmin on rat C6 glioma cells. In
      this investigation, we studied the response of C6 cells to alpha-thrombin and
      plasmin by measuring the rapid kinetics of free intracellular Ca2+ concentrations
      ([Ca2+]i). Thrombin produced a strong, concentration-dependent rise in [Ca2+]i
      with an onset within 3 s and peak levels achieved in less than 10 s. A similar
      response was also evoked by an SFLLRN-containing thrombin-agonist peptide. C6
      cells did not respond to plasmin (25 nM-1.5 microM). By contrast, pretreatment of
      C6 cells with 100 nM plasmin significantly inhibited the [Ca2+]i response to
      thrombin and the thrombin-agonist peptide. The peak [Ca2+]i response to thrombin,
      in cells pretreated with plasmin, was reduced by approx. 50%. The effect of
      plasmin on the cellular response to thrombin was selective, as pretreatment of
      the cells with plasmin did not affect the [Ca2+]i response to platelet-activating
      factor. Di-isopropylphosphorylplasmin and plasminogen did not inhibit the
      cellular response to thrombin, indicating that plasmin activity is required and
      that occupancy of cellular plasmin(ogen)-binding sites alone is insufficient.
      These studies demonstrate that plasmin does not directly induce a response in C6
      cells, but may affect cellular function by specifically modulating the thrombin
      response.

PMID- 8280097
TI  - Phospholipase C in Dictyostelium discoideum. Cyclic AMP surface receptor and G
      protein-regulated activity in vitro.
AB  - The cellular slime mould Dictyostelium discoideum shows several responses after
      stimulation with the chemoattractant cAMP, including a transient rise in cyclic
      AMP (cAMP), cGMP and Ins(1,4,5)P3. In this paper the regulation of phospholipase
      C in vitro is described. Under our experimental conditions commercial
      PtdIns(4,5)P2 cannot be used to analyse phospholipase C activity in Dictyostelium
      lysates, because it is hydrolysed mainly to glycerophosphoinositol instead of
      Ins(1,4,5)P3. Enzyme activity was determined with endogenous unlabelled PtdInsP2
      as a substrate. The product was measured by isotope-dilution assay and identified
      as authentic Ins(1,4,5)P3. Since phospholipase C is strictly Ca(2+)-dependent,
      with an optimal concentration range of 1-100 microM, cell lysates were prepared
      in EGTA and the enzyme reaction was started by adding 10 microM free Ca2+.
      Phospholipase C activity increased 2-fold during Dictyostelium development up to
      8 h of starvation, after which the activity declined to less than 10% of the
      vegetative level. Enzyme activity in vitro increased up to 2-fold after
      stimulation of cells with the agonist cAMP in vivo. Addition of 10 microM
      guanosine 5'-[gamma-thio]triphosphate during lysis activated the enzyme to the
      same extent, and this effect was antagonized by guanosine 5'-[beta
      thio]diphosphate. These results strongly suggest that surface cAMP receptors and
      G-proteins regulate phospholipase C during Dictyostelium development.

PMID- 8280098
TI  - Phospholipase C in Dictyostelium discoideum. Identification of stimulatory and
      inhibitory surface receptors and G-proteins.
AB  - A combined biochemical and genetic approach was used to show that phospholipase C
      in the cellular slime mould Dictyostelium is under dual regulation by the
      chemoattractant cyclic AMP (cAMP). This dual regulation involves stimulatory and
      inhibitory surface receptors and G-proteins. In wild-type cells both cAMP and
      guanosine 5'-[gamma-thio]triphosphate (GTP[S]) stimulated phospholipase C. In
      contrast, mutant fgd A, lacking the G-protein alpha-subunit G alpha 2, showed no
      stimulation by either cAMP or GTP[S], indicating that G alpha 2 is the
      stimulatory G-protein. In mutant fgd C cAMP did not stimulate phospholipase C,
      but stimulation by GTP[S] was normal, suggesting that the defect in this mutant
      is upstream of the stimulatory G alpha 2. Inhibition of phospholipase C was
      achieved in wild-type cells by the partial antagonist 3'-deoxy-3'-aminoadenosine
      3',5'-phosphate (3'NH-cAMP). This inhibition was no longer observed in
      transformed cell lines lacking either the surface cAMP receptor cAR1 or the G
      protein alpha-subunit G alpha 1; in these cells the agonist cAMP still activated
      phospholipase C. These results indicate that Dictyostelium phospholipase C is
      regulated via a stimulatory and an inhibitory pathway. The inhibitory pathway is
      composed of the surface receptor cAR1 and the G-protein G1. The stimulatory
      pathway consists of an unknown cAMP receptor (possibly the fgd C gene product)
      and the G-protein G2.

PMID- 8280099
TI  - Purification and characterization of a novel dimeric 20 alpha-hydroxysteroid
      dehydrogenase from Tetrahymena pyriformis.
AB  - Tetrahymena pyriformis was found to exhibit high NADPH-dependent 20-oxosteroid
      reductase activity that converted 17 alpha-hydroxyprogesterone into 17 alpha,20
      alpha-dihydroxypregn-4-en-3-one. The enzyme was purified 400-fold from the
      cytosolic fraction. The purified enzyme with a specific activity of 6.4 mumol/min
      per mg of protein had an isoelectric point of 4.9 and M(r) of 68,000, and was
      composed of two subunits of equal size. The N-terminal sequence was determined to
      be LAKTVPLNDGTNFPIFGG. The enzyme reduced pregnanes and pregnanes possessing a 17
      alpha-hydroxy group to a greater extent than those without the hydroxy group, and
      oxidized 20 alpha-hydroxy groups of the steroids in the presence of NADP+. The Km
      values for 17 alpha-hydroxyprogesterone and 17 alpha-hydroxypregnenolone were 2.9
      and 3.4 microM respectively. Although the enzyme was inactive towards androgens
      and oestrogens with 3- or 17-oxo groups, it reduced several nonsteroidal carbonyl
      compounds and oxidized trans-benzene dihydrodiol. The enzyme activity was
      inhibited by synthetic oestrogens, barbiturates, aldose reductase inhibitors and
      quercitrin. Thus, this enzyme is a novel form of 20 alpha-hydroxysteroid
      dehydrogenase (EC 1.1.1.149) which structurally and functionally differs from the
      mammalian and bacterial enzymes.

PMID- 8280100
TI  - Cardiolipin biosynthesis in the isolated heart.
AB  - The pathway for the biosynthesis of new cardiolipin was investigated in the
      isolated perfused intact rat heart. Isolated rat hearts were perfused in the
      Langendorff mode for up to 60 min with Krebs-Henseleit buffer containing 0.1
      microM [U-14C]glycerol. Analysis of radioactivity incorporated into phospholipids
      in the organic phase revealed an increase in radioactivity incorporated into
      phosphatidylglycerol, cardiolipin and other phospholipids with time of perfusion.
      This was associated with a loss of radioactivity from phosphatidic acid. In
      contrast, perfusion of hearts for up to 60 min with 0.1 mM [1,(3)-3H]glycerol in
      the perfusate revealed an increased radioactivity associated with phosphatidic
      acid as well as cardiolipin, phosphatidylglycerol and other phospholipids.
      Perfusion of hearts for up to 60 min with [32P]Pi in the perfusate revealed a
      time-dependent increase in radioactivity associated with all phospholipids.
      Perfusion of hearts for up to 60 min with 0.1 microM or 0.1 mM glycerol in the
      perfusate did not affect the concentration of phosphatidic acid, cardiolipin or
      phosphatidylglycerol. To determine the rate-limiting step of cardiolipin
      biosynthesis, hearts were pulsed for 5 min with 0.1 microM [1,(3)-3H]glycerol and
      chased for up to 60 min with 0.1 microM glycerol in the perfusate. Radioactivity
      was maximum at the start of the chase in phosphatidic acid (and 1,2
      diacylglycerol), and was subsequently chased into phosphatidylinositol,
      phosphatidylglycerol and cardiolipin (and other phospholipids). Significant
      radioactivity in phosphatidylglycerol phosphate was not detected. Radioactivity
      in CDP-sn-1,2-diacylglycerol remained constant throughout the chase. The
      activities of the enzymes of the Kennedy pathway for cardiolipin biosynthesis in
      the heart were determined. On the basis of continuous-pulse and pulse-chase
      labelling studies it is postulated that the cardiac polyglycerophospholipids
      phosphatidylglycerol and cardiolipin are actively synthesized from newly
      synthesized phosphatidic acid via the Kennedy pathway. In addition, the results
      suggest that the rate-limiting step of cardiolipin biosynthesis in the intact
      heart is probably the conversion of phosphatidic acid into CDP-sn-1,2
      diacylglycerol.

PMID- 8280101
TI  - Hydrogen peroxide activates agonist-sensitive Ca(2+)-flux pathways in canine
      venous endothelial cells.
AB  - The effect of the biological oxidant H2O2 on purinergic-receptor-stimulated Ca2+
      signalling was determined in canine venous endothelial cells. H2O2 increased
      cytosolic free [Ca2+] ([Ca2+]i), the rate of rise of which was dose-dependently
      related to H2O2 concentration. The response of [Ca2+]i to H2O2 resulted in part
      from release of Ca2+ from internal stores. The H2O2-sensitive intracellular Ca2+
      pool was characterized in cells suspended in Ca(2+)-free/EGTA buffer and
      stimulated in sequence with H2O2 and ionomycin or ATP. Under this condition, the
      rank order of apparent compartment size sensitive to each compound was ionomycin
      > H2O2 > ATP. Stimulation of cells with H2O2 eliminated any response of [Ca2+]i
      to subsequent addition of ATP. To test more directly whether H2O2 accesses the
      inositol trisphosphate-sensitive Ca2+ store, cells were pretreated with
      thapsigargin, a selective inhibitor of that store's Ca2+ pump. Release of Ca2+
      from internal Ca2+ stores by H2O2 declined as the interval after thapsigargin
      addition increased, a finding that supports the contention that H2O2 accesses the
      inositol trisphosphate-sensitive Ca2+ store. H2O2-stimulated Ca2+ influx across
      the cell membrane was sensitive to Ni2+, La3+, and 1-(beta-[3-(4
      methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole HCl (SKF-96365), a
      selective inhibitor of the agonist-stimulated Ca(2+)-influx pathway. Ca2+ entry
      triggered by H2O2 appears to occur via the agonist-sensitive Ca2+ influx pathway.
      Together, these results suggest that H2O2, which is normally secreted by
      activated neutrophils and monocytes, may act as an intercellular messenger and
      stimulate Ca2+ signalling in target endothelial cells.

PMID- 8280102
TI  - The requirement for phospholipase A2 for activation of the assembled NADPH
      oxidase in human neutrophils.
AB  - Phospholipase A2 (PLA2) inhibitors suppressed simultaneously, in a dose-dependent
      manner, the activation of NADPH oxidase and the release of 3H-labelled
      arachidonic acid ([3H]AA) stimulated by either phorbol 12-myristate 13-acetate
      (PMA) or opsonized zymosan (OZ) in human neutrophils. In spite of total
      inhibition of superoxide production in the presence of the PLA2 inhibitors, 10
      microM bromophenacyl bromide (BPB) or 20 microM quinacrine, a maximal
      phosphorylation of p47 and translocation of p47 and p67 to the neutrophil
      membranes induced by PMA or OZ was observed. Addition of 10 microM free AA, which
      by itself did not stimulate superoxide generation, restored oxidase activity in
      neutrophils treated with PLA2 inhibitors. These findings indicate that
      phosphorylation and translocation of the cytosolic factors to the membranes are
      not sufficient for generating superoxide; a functional PLA2 is also needed to
      stimulate the oxidase activity. The inhibition of PLA2 activity did not prevent
      the phosphorylation of p47, suggesting that the location of PLA2 is downstream of
      and does not activate protein kinase C.

PMID- 8280104
TI  - Bradykinin-dependent activation of adenylate cyclase activity and cyclic AMP
      accumulation in tracheal smooth muscle occurs via protein kinase C-dependent and 
      independent pathways.
AB  - Treatment of cultured tracheal smooth-muscle cells (TSM) with phorbol 12
      myristate 13-acetate (PMA) (100 nM) or bradykinin (100 nM) elicited enhanced
      basal and guanosine 5'-[beta gamma-imido]-triphosphate-stimulated adenylate
      cyclase activities in subsequently isolated membranes. Combined stimulation of
      cells was non-additive, indicating that both agents activate adenylate cyclase
      via similar routes. Both PMA (100 nM) and bradykinin (100 nM) allowed the alpha
      subunit of Gs to act as a more favourable substrate for its cholera-toxin
      catalysed ADP-ribosylation in vitro. PMA was without effect on intracellular
      cyclic AMP in control cells. However, constitutive activation of Gs by treatment
      in vivo with cholera toxin (0.5 ng/ml, 18 h) sensitized the cells to PMA
      stimulation, resulting in a concentration-dependent increase in intracellular
      cyclic AMP accumulation (EC50 = 7.3 +/- 2.5 nM, n = 5). Bradykinin also elicited
      a concentration-dependent increase in intracellular cyclic AMP (EC50 = 63.3 +/-
      14.5 nM, n = 3). Constitutive activation of Gs resulted in an increased maximal
      response (10-fold) and potency (EC50 = 6.17 +/- 1.6 nM, n = 3) to bradykinin.
      This response was not affected by the B2-receptor antagonist, NPC567 [which
      selectively blocks bradykinin-stimulated phospholipase C (PLC), with minor
      activity against phospholipase D (PLD) activity]. Des-Arg9-bradykinin (a B1
      receptor agonist) was without activity. These results suggest that the receptor
      sub-type capable of activating PLD may also be stimulatory for cyclic AMP
      accumulation. Furthermore, pre-treatment of the cells with butan-l-ol (0.3%,
      v/v), which traps phosphatidate derived from PLD reactions, blocked the
      bradykinin-stimulated increase in intracellular cyclic AMP. These studies suggest
      that there may be a causal link between PLD-derived phosphatidate and the
      positive modulation of adenylate cyclase activity. In support of this, the
      concentration-dependence for bradykinin-stimulated adenylate cyclase activity was
      identical with that of bradykinin-stimulated phospholipase D activity (EC50 = 5
      nM). Bradykinin, but not PMA, was also capable of eliciting the inhibition of
      cyclic AMP phosphodiesterase activity in TSM cells (EC50 > 100 nM) via an
      unidentified mechanism. These studies indicate that cross-regulation between the
      cyclic AMP pathway and phospholipid-derived second messengers in TSM cells does
      not occur as a consequence of PLC-catalysed PtdIns(4,5)P2 hydrolysis, but may
      involve, in part, PLD-catalysed phosphatidylcholine hydrolysis.

PMID- 8280103
TI  - Diradylglycerols stimulate phospholipase A2 and subsequent exocytosis in ram
      spermatozoa. Evidence that the effect is not mediated via protein kinase C.
AB  - We tested the hypothesis that the role of diacylglycerol (DAG) in sperm acrosomal
      exocytosis is related to the activation of phospholipase A2, and that this effect
      is not mediated via protein kinase C. Treatment of [14C]arachidonic acid-labelled
      ram spermatozoa with Ca2+ and the ionophore A23187 stimulated both liberation of
      arachidonic acid and acrosomal exocytosis. No changes in [14C]DAG or
      [14C]monoacylglycerol were found after stimulation of spermatozoa, thus
      suggesting that arachidonic acid may be released exclusively via phospholipase
      A2. An increase in the endogenous levels of diradylglycerols (DRGs), resulting
      from exposure either to the DAG kinase inhibitor R 59022 or to exogenous 1-oleoyl
      2-acetyl-sn-glycerol or 1,2-dioctanoyl-sn-glycerol, led to an increase in both
      phospholipase A2 activity and exocytosis when cells were stimulated with A23187
      and Ca2+. Addition of DRGs that do not stimulate protein kinase C(1,3
      dioctanoylglycerol, 1-O-hexadecyl-2-acetyl-rac-glycerol) also resulted in an
      increase in phospholipase A2 activity and exocytosis. On the other hand, phorbol
      esters (phorbol 12,13-dibutyrate; phorbol 12-myristate 13-acetate) did not
      enhance enzyme activity or exocytosis. Finally, exposure to 1-O-hexadecyl-2-O
      methyl-rac-glycerol, a compound known to inhibit protein kinase C, did not affect
      phospholipase A2 activity or acrosomal exocytosis. We therefore conclude that in
      spermatozoa the messenger role of DAG is related to the activation of
      phospholipase A2, which in turn would generate an array of metabolites directly
      or indirectly involved in bringing about exocytosis of the acrosome.

PMID- 8280106
TI  - Experimental discrimination between proton leak and redox slip during
      mitochondrial electron transport.
AB  - By measuring the relationship between protonmotive force and the increment in
      oxygen consumption by mitochondria treated with submaximal amounts of uncoupler,
      we have experimentally tested four different models of imperfect coupling of
      oxidative phosphorylation. The results show that the increased rate of oxygen
      consumption at high protonmotive force is explained entirely by the dependence on
      protonmotive force of the passive proton leak conductance of the mitochondrial
      inner membrane. There is no measurable contribution from redox-slip reactions in
      the proton pumps caused by high protonmotive force. Neither is there any
      contribution from increased proton conductance of the membrane or increased redox
      slip in the respiratory chain caused by high turnover rates of the complexes.

PMID- 8280105
TI  - N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulphonamide (H-89) inhibits
      incorporation of choline into phosphatidylcholine via inhibition of choline
      kinase and has no effect on the phosphorylation of CTP:phosphocholine
      cytidylyltransferase.
AB  - We have shown previously that N-[2-bromocinnamyl(amino)-ethyl]-5
      isoquinolinesulphonamide (H-89), a selective inhibitor of cyclic-AMP-dependent
      protein kinase (PKA), inhibits phosphatidylcholine biosynthesis in HeLa cells. In
      the present study, we elucidated the mechanism underlying the described
      inhibition. Treatment of cells with 10 microM H-89 had no effect on the
      phosphorylation of CTP:phosphocholine cytidylyltransferase. However, H-89
      slightly affected the distribution of cytidylyltransferase between cytosol and
      membranes, but the cellular 1,2-diacylglycerol content was not influenced.
      Furthermore, pulse-chase experiments revealed that H-89 did not affect
      cytidylyltransferase activity. Instead, H-89 inhibited choline kinase, the enzyme
      catalysing the first step in the CDP-choline pathway. In the presence of 10
      microM H-89, choline kinase activity was inhibited by 36 +/- 7.6% in vitro.
      Additionally, the phosphorylation of choline to phosphocholine was inhibited by
      30 +/- 3% in cell-culture experiments. This inhibitory effect could be partly
      prevented by simultaneous addition of 10 microM forskolin, indicating that
      choline kinase is regulated in part by PKA activity.

PMID- 8280107
TI  - Desulphation of dextran sulphate during kidney ultrafiltration.
AB  - The renal clearance of [3H]dextran sulphate by the isolated perfused rat kidney
      was associated with desulphation of the molecule, as demonstrated by ion-exchange
      and affinity chromatography of material resident in both glomeruli and urine
      samples. This process also occurred in vivo. The molecular size distribution of
      glomerular dextran sulphate in the perfused kidney was indistinguishable from
      that in the perfusate, and although urinary material was smaller it remained
      macromolecular. Sulphatase activity was not detected in urine or in the perfusate
      of perfused kidneys, but was detected in glomerular and non-glomerular cortex
      fractions isolated by a sieving procedure. The identification of significant
      biochemical changes to dextran sulphate demonstrates that it does not function as
      an inert transport probe, and supports the concept of cellular involvement in the
      process of renal charge selectivity.

PMID- 8280108
TI  - Expression of a rat renal sodium-dependent dicarboxylate transporter in Xenopus
      oocytes.
AB  - Microinjection of mRNA isolated from rat kidney cortex into Xenopus laevis
      oocytes resulted in the expression of a Na(+)-dependent dicarboxylate
      transporter, as detected by uptake measurements with [14C]succinate as substrate.
      The expressed transporter showed an S-shaped Na(+)-dependence with half-maximal
      activation at 19-21 mM Na+ and a Hill coefficient between 2 and 3. Endogenous
      succinate uptake was not Na(+)-dependent. Na(+)-stimulated succinate uptake in
      mRNA-injected oocytes exhibited a maximum at pH 7.5, whereas endogenous Na(+)
      independent transporter was fastest at pH 8.5. The expressed dicarboxylate
      transporter also differed from the endogenous transporter in its sensitivity to
      citrate as well as dicarboxylates in trans and cis configurations. The expressed
      transporter resembled the renal basolateral transporter, especially with respect
      to affinity for succinate (Km 28 microM), activation by Na+, pH-dependence and
      substrate specificity. After injection of size-fractionated mRNA, succinate
      uptake was expressed by mRNA of 2-3 kb. Our results suggest expression of the
      basolateral Na(+)-dependent dicarboxylate transporter after injection of mRNA
      from rat kidney into Xenopus oocytes.

PMID- 8280109
TI  - Growth hormone decreases the response to anti-lipolytic agonists and decreases
      the levels of Gi2 in rat adipocytes.
AB  - The effect of growth hormone (GH) in vivo on the Gi-mediated anti-lipolytic
      signalling system of rat adipocytes has been investigated. Lowering of serum GH
      levels, by treatment of rats with an antiserum (anti-rGH) specific for rat GH,
      increased the sensitivity of adipocytes to the anti-lipolytic agonists N6
      phenylisopropyladenosine (PIA) and prostaglandin E1. This occurred in the absence
      of any change in PIA binding to adipocyte membranes. Immunoblot analysis of
      adipocyte membranes revealed that lowering of serum GH resulted in at least a 3
      fold increase in the levels of alpha-subunit of Gi2, but had no effect on the
      alpha-subunits of Gi1 and Gi3 nor on the 42 and 45 kDa forms of the alpha-subunit
      of Gs. Replenishment of serum GH, by concurrent administration of ovine GH to
      rats, prevented all of these effects of anti-rGH. It is concluded that GH down
      regulates the amount of Gi2 alpha-subunit in adipocyte membranes, resulting in a
      decrease in the sensitivity of the cells to anti-lipolytic agonists.

PMID- 8280110
TI  - Different pathways for control of Na+/H+ exchange via activation of the thrombin
      receptor.
AB  - The aim of the present study was to clarify the control of Na+/H+ exchange in
      platelets activated via the thrombin receptor. When human BCECF-loaded platelets
      were stimulated with the thrombin-receptor-activating peptide (TRAP; amino acid
      sequence SFLLRN), which activates the receptor independently of proteolysis, the
      cytosolic pH (pHi) rose from 7.13 +/- 0.04 (n = 6) to 7.27 +/- 0.04 (n = 5),
      followed by a rapid decrease to resting values. Trypsin, which cleaves the
      receptor, induced a rapid and irreversible rise in pHi to 7.31 +/- 0.06 (n = 5).
      gamma-Thrombin, which cleaves the receptor but is unable to bind to the hirudin
      like domain, induced a slow and irreversible rise in pHi to 7.31 +/- 0.04 (n =
      14). alpha-Thrombin, which cleaves the receptor and binds to its hirudin-like
      domain, induced a rapid and irreversible rise in pHi to 7.31 +/- 0.04 (n = 22).
      Changes in pHi induced by TRAP, trypsin, gamma- and alpha-thrombin were
      accompanied by similar changes in cytosolic Ca2+ concentration ([Ca2+]i) and 32P
      pleckstrin, a substrate of protein kinase C (PKC). The separate chelation of
      Ca2+i (30 microM BAPTA-AM) or inhibition of PKC (1 microM staurosporine) induced
      about 50% inhibition of the pHi responses triggered by TRAP, trypsin, gamma- and
      alpha-thrombin, but the combination induced complete inhibition. Thus the
      different types of activation of the thrombin receptor control Na+/H+ exchange
      via the same mechanism. Binding of thrombin to the hirudin-like domain
      accelerates exchange activation, whereas proteolysis of the receptor is essential
      for a sustained increase in pHi.

PMID- 8280111
TI  - Co-variation of glutathione transferase expression and cytostatic drug resistance
      in HeLa cells: establishment of class Mu glutathione transferase M3-3 as the
      dominating isoenzyme.
AB  - Qualitative and quantitative analyses of glutathione, glutathione transferases
      (GSTs) and other glutathione-linked enzymes in HeLa cells have been made in order
      to study their significance in cellular resistance to electrophilic cytotoxic
      agents. The cytosolic concentrations of three GSTs, GST M1-1 (53 +/- 9 ng/mg of
      cytosolic protein), GST P1-1 (11 +/- 3 ng/mg) and GST A1-1 (1.1 +/- 0.4 ng/mg)
      were quantified by isoenzyme-specific enzyme-linked immunoassays. Electrophoretic
      analysis and immunoblotting demonstrated another component, GST M3-3, which was
      identified by amino acid sequence analysis. GST M3-3 was quantified (1550 +/- 250
      ng/mg) by slot-blot immunoanalysis and was the most abundant GST in HeLa cells.
      An additional cytosolic 13 kDa protein with high affinity for immobilized
      glutathione or S-hexyglutathione was found to be identical with a macrophage
      migration-inhibitory factor, previously identified as a lymphokine. Cells grown
      in roller bottles (HR) rather than in ordinary culture flasks contain a
      significantly lower concentration of all the GSTs and were found to be more
      sensitive to the cytostatic agents doxorubicin (2.3-fold), cisplatin (1.7-fold)
      and melphalan (1.4-fold). The cytosolic concentrations of glutathione reductase
      and glyoxalase I were also lower in HR cells, whereas the total glutathione
      concentration was unchanged and the glutathione peroxidase activity was
      increased. The results indicate that GSTs contribute to the cellular resistance
      phenotype.

PMID- 8280112
TI  - Glutamine synthesis from glucose and ammonium chloride by guinea-pig kidney
      tubules.
AB  - 1. At a physiological concentration (5 mM), glucose was found to be metabolized
      by isolated kidney cortex tubules prepared from fed guinea pigs. 2. The release
      of 14CO2 from [U-14C]glucose indicated that oxidation of the glucose carbon
      skeleton represented about 50% of the glucose removed; significant amounts of
      lactate and glutamine also accumulated. 3. Addition of 0.1-10 mM NH4Cl led to a
      dose-dependent stimulation of glucose metabolism which was accompanied by a large
      increase in lactate and glutamine accumulation and, to a lesser extent, in
      glucose oxidation. 4. Comparison of the release of 14CO2 from [1-14C]- and [6
      14C]glucose indicates that, in both the absence and the presence of NH4Cl, the
      pentose phosphate shunt was only a minor pathway of glucose metabolism. 5. The
      central role of pyruvate carboxylase in the conversion of glucose carbon into
      glutamine carbon was demonstrated by using a bicarbonate-free medium and
      measuring the fixation of 14CO2 from [14C]bicarbonate, which was recovered mostly
      at C-1 of glutamine plus glutamate. 6. The NH4Cl-induced stimulation of glucose
      removal was secondary not only to increased glutamine synthesis, as shown by the
      effect of methionine sulphoximine, an inhibitor of glutamine synthetase, but also
      to the stimulation of phosphofructokinase activity by NH4Cl. 7. Renal arterio
      venous difference measurements revealed that, in vivo, the guinea-pig kidney
      removed glucose from the circulating blood, which suggests that glucose carbon
      may contribute to the carbon skeleton of the glutamine released by this organ.

PMID- 8280113
TI  - Bacterial expression of Chinese hamster regulatory type-I and catalytic subunits
      of cyclic AMP-dependent protein kinase and mutational analysis of the type-I
      regulatory subunit.
AB  - The type-I regulatory subunit (RI) of the cyclic AMP-dependent protein kinase
      (PKA) from Chinese hamster ovary (CHO) cells has been cloned and expressed in a
      strain of BL21(DE3) Escherichia coli lacking adenylate cyclase [BL21(DE3)/delta
      cya]. RI expressed in this bacterial system free of cyclic AMP is soluble and can
      reconstitute functional PKA. Recombinant CHO C alpha is predominantly insoluble
      with some active soluble protein. C beta is entirely insoluble and inactive.
      Soluble recombinant RI and soluble recombinant C alpha can associate in vitro and
      be activated by cyclic AMP. Six site-directed mutations of RI were generated to
      study the interaction of cyclic AMP with RI and RI-C alpha subunit interactions.
      Four cyclic AMP-binding-site point mutants were generated [W261R (tryptophan to
      arginine at position 261), a novel mutation in site A; V376G, a novel mutation in
      site B; G200E (site A), and Y370F (site B), previously described in bovine RI
      were introduced into the CHO RI for comparison purposes]. Mutants W261R, Y370F,
      and G200E demonstrated decreased 8-N3-[3H]cyclic AMP binding as well as 5-fold
      reduced affinity for [3H]cyclic AMP, with threefold increased EC50 values for
      cyclic AMP activation of kinase activity from reconstituted mutant holoenzymes.
      The mutation at V376G did not alter cyclic AMP binding or activation by cyclic
      AMP of mutant holoenzyme. A truncation mutant, G200Stop, which lacks both cyclic
      AMP-binding sites, did not bind cyclic AMP but can inhibit C alpha subunit
      activity. A novel mutation outside the cyclic AMP-binding regions of RI (V89A)
      weakened the interaction with C alpha indicated by a 7-fold lower EC50 for mutant
      holoenzyme activation by cyclic AMP.

PMID- 8280114
TI  - Identification of a binding site on retinal transducin alpha for the
      phosphodiesterase inhibitory gamma subunit.
AB  - Transducin alpha (T alpha) activates retinal rod cyclic GMP phosphodiesterase
      (PDE) by interacting with and removing the inhibitory PDE gamma subunit. A T
      alpha-PDE gamma complex can be isolated in vitro, and our previous work
      [Morrison, Rider and Takemoto (1987) FEBS Lett. 222, 266-270; Morrison, Cunnick,
      Oppert and Takemoto (1989) J. Biol. Chem. 264, 11671-11681] has identified a
      region of PDE gamma, residues 24-45, that binds to T alpha. The C-terminal region
      of PDE gamma is the site that interacts with PDE alpha/beta and inhibits
      catalytic function. The site on T alpha that binds to the PDE gamma 24-45 region
      has not been identified. Synthetic peptides (15-mers) which span the bovine T
      alpha sequence were tested for binding to purified recombinant PDE gamma using a
      solid-phase assay. The peptides were also tested for ability to activate a PDE
      complex. We have identified a region, residues 250-275 of T alpha, which shows a
      high affinity of PDE gamma and for the PDE gamma (24-45) binding peptide. The
      peptide did not bind to the C-terminal residues 50-87 of PDE gamma. Likewise, a
      region of T alpha, 1-25 did not exhibit high-affinity binding to PDE gamma or to
      the 24-45 PDE gamma peptide. Specific binding of the 250-275 peptide to PDE gamma
      was confirmed by its ability to compete with T alpha binding to PDE gamma,
      although a higher concentration was required (10x). The T alpha-(250-275) peptide
      activated a fully inhibited PDE alpha beta gamma 2 complex in a dose-dependent
      manner. These results suggest that a region on T alpha that recognizes the PDE
      gamma-binding site is found within residues 250-275 of T alpha.

PMID- 8280115
TI  - Studies on cytochrome c-heparin interactions by differential scanning
      calorimetry.
AB  - The effects of heparin on the thermotropic properties of ferricytochrome c have
      been studied using high-sensitivity differential scanning calorimetry. Saturating
      concentrations of heparin at low ionic strength induced an important shift of the
      transition temperature Tm from 84.1 degrees C to 59.8 degrees C. This was
      accompanied by unusually large cooperativity of thermal denaturation of this
      complex, indicating strong intermolecular interactions between protein molecules.
      The destabilization of cytochrome c when mixed with heparin was not observed at
      high ionic strength, under which conditions complex was not formed.

PMID- 8280116
TI  - A monoclonal antibody reactive with terminal lactotriaosyl residue-containing
      oligosaccharides and its application to characterizing cell surface expression of
      the glyco-epitopes in COS-1 cells.
AB  - A new monoclonal antibody (MoAb), designated JF12, reactive strongly with Lc3
      (GlcNAc beta 1-->3Gal beta 1-->4Glc beta 1-->Cer) but only slightly with nLc5
      (GlcNAc beta 1-->3Gal beta 1-->4GlcNAc beta 1-->3Gal beta 1-->4Glc beta 1-->Cer)
      has been prepared after immunization of Balb/c mice with Lc3. By the
      flowcytometrical analyses of COS-1 cells, which was strongly stained with JF12,
      the reactivity completely disappeared in the confluent condition upon harvesting
      by the protease treatments of the cell surface. In the sparse condition, however,
      the cells still retained JF12 reactivity in spite of the protease treatments.
      This strongly suggests that the expression of terminal GlcNAc-containing
      glycoconjugates on the surface of COS-1 cells may be dramatically modulated by
      protease-sensitive membranous components being dependent upon the cell density.

PMID- 8280117
TI  - Blood-brain barrier transport of circulating Alzheimer's amyloid beta.
AB  - The origin of amyloid beta (A beta) deposited in brain and cerebral blood vessels
      of patients with Alzheimer's Disease (AD) is not known. In this study, we tested
      whether soluble A beta (sA beta) can cross the blood-brain barrier (BBB). An in
      vivo vascular brain perfusion model and capillary depletion technique in guinea
      pigs were used to determine cerebral capillary sequestration and blood-brain
      transport of a synthetic peptide identical with residues 1-40 (SP-40) of A beta.
      A saturable, specific binding of SP-40 has been demonstrated at the luminal side
      of the BBB, with the Kd of 25 +/- 2 nM, and Bmax of 188 +/- 11 fmol/min/g of
      isolated microvessels. A specific transcellular BBB transport of SP-40 into brain
      parenchyma exhibited the Km of 49 +/- 10 nM, and Vmax of 111 +/- 19 fmol/min/g of
      capillary depleted brain. We concluded that the BBB has the capability to control
      the cerebrovascular sequestration and blood-to-brain transport of circulating sA
      beta. Hence, sA beta can contribute to both cerebrovascular and parenchymal
      amyloid formation.

PMID- 8280118
TI  - Bovine prostacyclin synthase: purification and isolation of partial cDNA.
AB  - Prostacyclin synthase (PGIS) from bovine aorta was purified using conventional
      purification procedures including detergent solubilization, Sephacryl S-300 gel
      filtration and Mono Q high performance liquid chromatography. Polyclonal
      antiserum raised against the 52-kDa protein bound specifically to PGIS. After
      immobilization to Protein A-sepharose, the PGIS-antibody complex displayed PGIS
      activity. Results based on (1) elution profile of the Mono Q column, (2) two
      dimensional gel electrophoresis and (3) N-terminal amino acid sequence suggested
      that PGIS is heterogenous. Amino acid sequences of N-terminus and a tryptic
      peptide led us to isolate a partial cDNA fragment.

PMID- 8280119
TI  - Accumulation of mtDNA with a mutation at position 3271 in tRNA(Leu)(UUR) gene
      introduced from a MELAS patient to HeLa cells lacking mtDNA results in
      progressive inhibition of mitochondrial respiratory function.
AB  - A new mitochondrial DNA (mtDNA) mutation of tRNA(Leu)(UUR) at nucleotide position
      3271 (MELAS3271) was determined to be involved in the pathogenic process of
      mitochondrial diseases MELAS (mitochondrial myopathy, encephalopathy, lactic
      acidosis and stroke-like episodes) using intercellular transfer of patient
      derived mtDNA to mtDNA-less HeLa cells (rho 0 HeLa cells). Cybrid clones
      containing imported mtDNA exclusively from a MELAS patient with MELAS3271 mtDNA
      were isolated, and the influence of MELAS3271 mtDNA on mitochondrial translation
      activity and mitochondrial respiratory complex I enzyme activity were examined.
      Accumulation of more than 87% MELAS3271 mutant mtDNA in the cybrid clones induced
      both low complex I activity and abnormal mtDNA-encoded polypeptide synthesis
      including at least complex I subunit ND6. suggesting involvement of the new MELAS
      associated mutation in the pathogenesis.

PMID- 8280120
TI  - Purification and characterization of a novel tetradecapeptide that modulates
      oesophagus motility in Lymnaea stagnalis.
AB  - The isolated oesophagus of Lymnaea stagnalis was used as a bioassay preparation
      to identify peptides that modulate the activity of the oesophagus. Several
      modulatory messengers were detected from the oesophageal extract. One of these,
      having an excitatory action, was further purified from both the oesophagus and
      the central nervous system through high performance gel permeation chromatography
      followed by serial reversed phase high performance liquid chromatography. The
      purified peptide was chemically characterized through amino acid sequencing and
      mass spectrometry as GFRANSASRVAHGY-NH2.

PMID- 8280121
TI  - Molecular cloning of a novel, putative G protein-coupled receptor from sea
      anemones structurally related to members of the FSH, TSH, LH/CG receptor family
      from mammals.
AB  - Using oligonucleotide probes derived from consensus sequences of known vertebrate
      and invertebrate G protein-coupled receptors, we have cloned the cDNA for a
      presumed G protein-coupled receptor from sea anemones. This receptor shows a
      striking structural homology with members of the glycoprotein hormone (FSH, TSH,
      LH/CG) receptor family from mammals, including a very large, extracellular N
      terminus (18-25% sequence identity) and a 7 transmembrane region (44-48% sequence
      identity). As with the mammalian glycoprotein hormone receptor genes, the sea
      anemone receptor gene yields transcripts which can be alternatively spliced,
      thereby yielding a shortened receptor variant only containing the large
      extracellular (soluble) N terminus. All this is strong evidence that the putative
      glycoprotein hormone receptor from sea anemones is evolutionarily related to
      those from mammals. This is the first report showing that a putative glycoprotein
      hormone receptor occurs in invertebrates.

PMID- 8280122
TI  - Pioglitazone ameliorates high glucose induced desensitization of insulin receptor
      kinase in Rat 1 fibroblasts in culture.
AB  - A new oral agent, pioglitazone, increases insulin sensitivity by activating
      receptor kinase in insulin-resistant rats. To clarify the mechanism, we studied
      in vitro effects of glucose and pioglitazone on the insulin receptor function
      using Rat 1 fibroblasts which expressed human insulin receptors. Insulin receptor
      kinase activity was impaired by incubating cells for 4 days in the presence of
      27mM D-glucose. The glucose effect was time- and dose-dependent and also specific
      for D-glucose, since D-raffinose incubation had no effect. Pioglitazone treatment
      did not have any effect on intact receptor kinase. However, exposure of both 27mM
      D-glucose and 0.1 microM pioglitazone to the cells completely prevented the
      glucose-induced impairment of insulin receptor kinase activity, suggesting that
      pioglitazone might reverse the processes which are critical for the glucose
      induced desensitization of insulin receptor kinase.

PMID- 8280123
TI  - Hereditary error in epidermal growth factor prohormone metabolism in a rat model
      of autosomal dominant polycystic kidney disease.
AB  - Normal Sprague Dawley (SPRD) rats of both sexes secrete an 165 kDa EGF prohormone
      in urine. Sexually mature Hannover-Sprague Dawley rats (Han:SPRD) heterozygous
      males and females with autosomal dominant polycystic kidney disease (ADPKD)
      secrete a prohormone of similar molecular mass in urine. The male, but not the
      female, also secretes two variant prohormone isoforms with molecular masses close
      to 200 kDa. Both the 165 and 200 kDa EGF prohormone isoforms are totally absent,
      in urine, at 11 months of age in male but not in female heterozygous Han:SPRD
      rats. At this age, the male kidneys exhibit numerous cysts filled with colorless
      fluids and these fluids contain abundant quantities of a 66 kDa EGF prohormone
      metabolite. Homozygous Han:SPRD rats which are born with cystic disease secrete
      only trace amounts of 165 kDa EGF prohormone in their urine while their normal
      looking littermates secrete the 165 kDa EGF prohormone in abundant quantities.
      The cyst fluids of homozygous rats contain trace amounts of 165 and 154 kDa EGF
      prohormone isoforms while the 66 kDa EGF prohormone metabolites present in
      abundant quantities. The massive amounts of 66 kDa EGF prohormone metabolite in
      cyst fluids of PKD rats suggests that EGF prohormone and its isoforms undergo
      aberrant proteolysis in association with cyst pathogenesis both in heterozygous
      and homozygous kidneys. The specific retention of the 66 kDa EGF prohormone
      metabolite within the cyst suggests that this molecule may function as a
      cystogen.

PMID- 8280124
TI  - Elevation of serum albumin by intrahepatic transplantation of albumin-producing
      cells does not correct quantitative abnormalities of non-albumin proteins in
      analbuminemic rats.
AB  - Nagase analbuminemic rats (NAR) show quantitative abnormalities of non-albumin
      serum proteins which could represent a compensatory response to the
      analbuminemia, although total serum protein levels are normal. When hyperplastic
      hepatic nodule (HPN) cells of F344 rats, which produce albumin, were infused into
      the portal vein of congenic analbuminemic rats (F344-alb) followed by treatment
      with the Solt and Farber dietary regimen, the transplanted cells grew within the
      livers, occasionally developing into hepatocellular carcinomas (HCC). In the
      recipient F344-alb, while serum albumin was considerably elevated, the total
      serum protein was also increased. Moreover, the abnormal pattern of serum
      proteins in NAR was unchanged by the elevation of albumin. These results indicate
      that the unique pattern of serum proteins in NAR is constitutive and cannot be
      corrected by a continuous increase in albumin levels.

PMID- 8280125
TI  - Evidence for identity of beta-pyrazolealanine synthase with cysteine synthase in
      watermelon: formation of beta-pyrazole-alanine by cloned cysteine synthase in
      vitro and in vivo.
AB  - The responsibility of cysteine synthase (EC 4.2.99.8) from watermelon (Citrullus
      vulgaris) for the formation of beta-(pyrazole-1-yl)-L-alanine, a non-protein
      amino acid specifically accumulated in Curcubitaceae plants, was confirmed in
      vitro and in vivo by the cloned cDNA on expression vectors, pCCS11 and pCEN1. The
      cDNA sequence derived from pCCS11, an expression vector driven by the lacZ
      promoter, was placed under the transcriptional control of strong T7 promoter of
      pET3d to yield an over-expression vector, pCEN1, in Escherichia coli. The
      concentration of the exogenous cysteine synthase protein was increased up to
      approximately 10% of the total soluble protein of E. coli cells by the expression
      of cDNA on pCEN1. beta-(Pyrazole-1-yl)-L-alanine was formed in vitro from O
      acetyl-L-serine and pyrazole by the action of cysteine synthase expressed in E.
      coli carrying pCCS11 or pCEN1. To confirm the responsibility of cysteine synthase
      for the formation of beta-(pyrazole-1-yl)-L-alanine in vivo, the feeding
      experiments of pyrazole and serine or O-acetyl-L-serine were carried out using
      the transformed E. coli culture. beta-(Pyrazole-1-yl)-L-alanine was produced in
      vivo by feeding the substrates to the culture of E. coli carrying pCEN1. These
      results provide the confirming evidence that the cloned cysteine synthase of
      watermelon catalyzes the formation of beta-(pyrazole-1-yl)-L-alanine, indicating
      that beta-pyrazolealanine synthase is identical with cysteine synthase in
      Cucurbitaceae plants.

PMID- 8280126
TI  - Isolation and characterization of membrane-associated form of penicillase plasmid
      (pI524) DNA in Staphylococcus aureus.
AB  - Our studies on the association of penicillinase plasmid (pI524) DNA with its host
      bacterial (Staphylococcus aureus) membrane revealed that the membrane-associated
      forms of this plasmid could be isolated from exponentially grown cells lysed on
      neutral sucrose gradient. Analysis of putative plasmid-membrane complexes
      isolated from the clear lysates on sucrose gradients indicated that approximately
      23% of plasmid (pI524) DNA was stably associated with the bacterial cell membrane
      fractions. This suggested that one of the three or four copies of this plasmid
      per cell was complexed to the cellular membrane. Examination of the effect of
      various enzymes, e.g., ribonuclease and protease, as well as antibiotics
      (rifampicin and chloramphenicol), on complexing have shown the possible
      involvement of protein(s) rather than RNA in mediating the complexing of this
      plasmid to the cell membrane. The specificity of plasmid pI524 to its host cell
      membrane was observed in an experiment where R6k was included in binding assay.

PMID- 8280127
TI  - Identification and stabilization of large molecular weight PDE-IVs from U937
      cells.
AB  - Cytosolic cyclic nucleotide phosphodiesterases (PDEs) from human (promonocytic)
      U937 cells were rapidly resolved by DEAE-Sepharose CL-6B anion exchange
      chromatography into two major peaks of cAMP-specific activity possessing average
      Kms of 1.70 microM (Peak 1) and 1.65 microM (Peak 2). Both peaks were
      predominantly PDE-IV, but possessed molecular weights higher than those generally
      reported for partially purified PDE-IVs. Storage of Peak 2 for 24 h at 4 degrees
      C resulted in a doubling of its Vmax and an apparent decrease in its molecular
      weight. Activation of Peak 2 PDE-IV was prevented when the sodium acetate
      concentration in its buffer was reduced by dilution immediately following
      isolation. Although the relevance of this activation to cellular regulation of
      PDE-IV is undefined, the isolation and stabilization of PDE-IV in its large
      molecular weight form will be critical to future investigations of PDE-IV
      regulation.

PMID- 8280128
TI  - Lack of copper binding sites in ceruloplasmin of LEC rats with abnormal copper
      metabolism.
AB  - Recently it was found that the clinical features of the LEC rat closely resemble
      those of human Wilson's disease. One of the characteristics of the animal is low
      levels of serum ceruloplasmin. Therefore, by using LEC rats, we attempted to
      define molecular basis of the deficiency in active site of ceruloplasmin in
      Wilson's disease patients. We made 3 monoclonal antibodies, ID2 against active
      site of ceruloplasmin, ID1 against inactive site of ceruloplasmin, and the
      remaining one against metallothionein. Using these monoclonal antibodies, we
      examined immunohistochemical stainings of LEC rat liver tissues, and compared
      them with those of LEA rats, as a control. ID1 stained the hepatocytes of both
      LEA and LEC rats, whereas ID2 stained LEA rat hepatocytes only. The results
      indicated that the ceruloplasmin secreted by LEC rat hepatocytes is mostly in
      inactive form. The antibody against metallothionein stained LEA rat hepatocytes
      only. This finding may also indicate that LEC rat hepatocytes express less amount
      of metallothionein than those of LEA rats.

PMID- 8280129
TI  - Repression of glucocorticoid receptor function by the anti-rheumatic gold
      compound aurothiomalate.
AB  - We describe functional interaction between the anti-rheumatic water-soluble gold
      compound aurothiomalate and glucocorticoid receptors. Aurothiomalate contains
      gold in the Au(I) state, and Au(I) alone, not thiomalate or malate, reduced the
      ligand-binding activity of the glucocorticoid receptor. Au(I) also interfered
      with the productive interaction between the glucocorticoid receptor and the
      cognate target DNA sequences and repressed the transactivation function of the
      receptor. Thus, Au(I) variably modulates glucocorticoid receptor-mediated
      intracellular signals.

PMID- 8280130
TI  - In vitro processing by signal peptidase I of precursor maltose-binding protein
      species with alterations in and around the signal peptide.
AB  - Processing of 37 precursor maltose-binding protein (preMBP) species by purified
      signal peptidase I (SPase I) was assayed. The in vitro reaction was inefficient
      compared to processing in Escherichia coli cells. The extent of preMBP processing
      in vitro was higher when SPase I was present during translation as compared to
      processing after translation was arrested by chloramphenicol. Complete conversion
      of wild-type (wt) preMBP (greater than 90%) to mature protein required 4300-fold
      more enzyme than substrate during a 15 min reaction. Most preMBP species with
      alterations in the signal peptide processing region that were efficiently
      processed (greater than 85%) in vivo were also processed in vitro, although the
      efficiency of processing was usually lower than the corresponding in vivo value.
      Increasing the level of SPase I in the in vitro reaction often increased the
      extent of preMBP processing. A number of amino acid substitutions in the
      processing region that drastically reduced or eliminated processing in vivo also
      eliminated processing in vitro. Processing occurred at an alternate site in some
      mutant preMBP species in vivo, but this event occurred very inefficiently in
      vitro. Amino acid substitutions in the hydrophobic core or in the charged regions
      at the N-terminus of the signal peptide and early mature region of preMBP
      slightly reduced in vitro processing as compared to processing of wt preMBP,
      regardless of their effect on secretion in vivo.

PMID- 8280131
TI  - Identification of a hyperactive mating pheromone of Saccharomyces cerevisiae.
AB  - The yeast mating pheromone a-factor is a farnesylated peptide
      [YIIKGVFWDPAC(Farnesyl)-OCH3] involved in the signal transduction cascade which
      leads to sexual conjugation of haploid cells. We have identified a synthetic
      analog of the a-factor, [D-Ala5] a-factor, which exhibits 4-6 fold greater
      biological activity than that of a-factor as judged by two different assay
      systems. In contrast, [L-Ala5] a-factor has 4-16 fold lower activity than wild
      type a-factor. [D-Ala5] a-factor remains susceptible to cleavage by the yeast
      alpha-cell specific protease a-factorase, thereby ruling out increased activity
      due to greater stability. This report describes the first example of a
      hyperactive S. cerevisiae pheromone and may suggest a conformationally preferred
      form of this lipopeptide ligand.

PMID- 8280132
TI  - The selective protein kinase C inhibitor GF 109203X inhibits phorbol ester
      induced morphological and functional differentiation of SH-SY5Y human
      neuroblastoma cells.
AB  - Previous attempts to inhibit the phorbol ester 12-O-tetradecanoyl phorbol 13
      acetate (TPA) -induced differentiation of SH-SY5Y neuroblastoma cells by non
      specific inhibitors of protein kinases have failed. In the present study we have
      used the bisindolylmaleimide GF 109203X, which is a potent and selective
      inhibitor of protein kinase C (PKC). GF 109203X effectively antagonized TPA
      stimulated phosphorylation of an endogenous 80 kDa PKC substrate. The compound
      blocked neurite outgrowth and rounding up of cells induced by the phorbol ester.
      In addition, GF 109203X completely inhibited TPA-induced increase in cellular
      content of noradrenaline as well as stimulation of expression of neuropeptide Y,
      growth-associated protein-43 and c-fos proto-oncogene mRNA by TPA. The inhibition
      of the TPA-induced effects by GF 109203X was dose-dependent.

PMID- 8280133
TI  - Effect of SV40 and MMTV promoters on intermolecular homologous recombination in
      rat cells.
AB  - The effect of SV40 and MMTV promoters on intermolecular homologous recombination
      between neomycin (neo) genes carrying deletions proximal and distal to the
      promoters has been examined in rat XC cells. One deleted neo gene linked to
      either promoter and the other deleted one without any promoter were co
      transfected to cells so that the number of resulting G418-resistant colonies
      reflected the frequency at which the promoter-linked neo allele had been
      corrected by homologous recombination. We found that when the the distal deletion
      was placed under the SV40 promoter, it was corrected over 20-fold more frequently
      than the proximal. In contrast, when the MMTV promoter replaced the SV40
      promoter, the distal deletion was corrected only 2-fold frequently compared with
      the proximal, and this result did not alter by activating the promoter with a
      glucocorticoid hormone dexamethasone. These results suggest that the preferential
      gene correction event observed with the SV40 promoter is attributed not to the
      transcriptional activity but to some specific sequence of the promoter.

PMID- 8280134
TI  - The inhibition of the inositol 1,4,5-trisphosphate receptor from rat cerebellum
      by spermine and other polyamines.
AB  - Inositol 1,4,5-trisphosphate-induced Ca2+ release from rat cerebellar microsomes
      can be inhibited by polyamines at mM concentrations. Spermine, one of the most
      abundant naturally occurring polyamines, inhibits InsP3-induced Ca2+ release with
      an IC50 of 1 mM. However, the antibiotic neomycin proved most efficacious at
      inhibiting InsP3-induced Ca2+ release (IC50 0.4mM). The order of potency being
      neomycin > spermine > spermidine > putrescine. Although binding of [3H]InsP3 to
      cerebellar microsomes is also inhibited by polyamines, this may be due to InsP3
      complexing with the polyamines under the binding conditions used. Under Ca2+
      release conditions InsP3 binds weakly to spermine and therefore inhibition of
      InsP3-induced Ca2+ release is consistent with polyamines interacting with the
      InsP3 receptor.

PMID- 8280135
TI  - Transactivating function of integrated hepatitis B virus.
AB  - HBV DNAs are often found in integrated forms in human hepatocellular carcinoma
      (HCC). Discovery of a transactivation function coded by a limited region of the
      HBV genome has promoted us to survey our collection of HBV integrants with
      flanking cellular sequences, asking whether they might exhibit a transactivation
      function. In transient cotransfection assays using the HepG2 cell line, six out
      of the twelve integrants showed transactivation effects on the expression of
      cellular genes such as c-fos. These results strongly demonstrate that the
      transactivating effects of integrated HBV DNA are widely distributed, and some of
      these effects might be correlated to hepatocarcinogenesis.

PMID- 8280136
TI  - Dissociation of the peptide/MHC class I complex: pH dependence and effect of
      endogenous peptides on the activation energy.
AB  - Dansylated peptides were used to characterize the dissociation of peptides from a
      recombinant class I major histocompatibility complex protein. Dissociation of
      endogenous, low-affinity peptides from the class I molecule Kd had an activation
      energy of 6.78 +/- 0.64 kcal/mol in the 14 to 26 degrees C temperature range, but
      there was a break in the Arrhenius plot between 12 and 14 degrees C. Dissociation
      of a dansylated, high-affinity peptide had an activation energy of 20.24 +/- 1.69
      kcal/mol, and there was similarly a break in the plot. Both direct interactions
      between peptide and the class I heavy chain and indirect effects of the peptide
      affinity on the extent of light chain association with heavy chain may contribute
      to the difference in activation energies, while the break in the Arrhenius plots
      implies a temperature-dependent conformational change. Dissociation was also
      slowest at neutral pH, but the peptide/class I complex dissociated rapidly at pH
      greater than 9 and less than 5, suggesting that endocytosed class I proteins
      would most likely lose their bound peptides at the acidic pH of endosomes.

PMID- 8280137
TI  - Sequence specific binding of the transcription factor c-Ets1 to the human
      immunodeficiency virus type I long terminal repeat.
AB  - Human immunodeficiency virus type I (HIV-1) long terminal repeat (LTR) driven
      transcription is regulated by a variety of cellular transcription factors. Most
      work has focused on the two nuclear factor kappa B (NF-kB) elements indispensable
      for HIV-1 LTR enhancer function. We demonstrate here the specific binding of the
      transcription factor c-Ets1 to an U3 region of the HIV-1 LTR (nt -141 to -149)
      using electrophoretic mobility shift analysis with T-cell nuclear extract and in
      vitro translated protein. This previously not identified Ets binding site is
      highly conserved among different HIV-1 isolates and maps to an U3 region recently
      shown to be necessary for viral growth in vitro. The c-Ets proto-oncogene family
      of transcription factors has yet been associated with HTLV-I and HIV-2
      transcription. Our present analysis suggests an important role of c-Ets proteins
      in HIV-1 transcription.

PMID- 8280138
TI  - The inward rectifier and two levels of the membrane potential in human term
      placental cells.
AB  - Whole-cell variations of patch-clamp techniques were applied to human term
      placental cells. The inward rectifier K currents were recorded. The current
      voltage relationship in some cells crossed the voltage axis at two different
      potentials. Such cells showed two stable levels of the membrane potential. The
      current-clamp method could switch the membrane potentials between those two
      levels. The present results provide evidence that the inward rectifier K
      conductance could set two changeable levels of the membrane potential in some
      human term placental cells.

PMID- 8280139
TI  - Identification of defect in the genes for bilirubin UDP-glucuronosyl-transferase
      in a patient with Crigler-Najjar syndrome type II.
AB  - Crigler-Najjar syndrome (CN) type II is characterized by severe chronic
      nonhemolytic unconjugated hyperbilirubinemia due to reduced hepatic bilirubin UDP
      glucuronosyl-transferase (UGT) activity. Two bilirubin UGT isozymes, UGT1A and
      UGT1D, have been identified. We analyzed the DNA sequence of the bilirubin UGT
      genes in a 5-year-old Japanese male patient with CN type II, who had
      consanguineous parents. Point mutations were found on exons 1 of the UGT1A and
      UGT1D genes. The abnormalities were single nucleotide substitutions of G by A and
      of T by C at base position 211 of UGT1A cDNA and at base position 395 of the
      UGT1D, respectively. We found another single nucleotide substitution of T by G on
      exon 5 common to both genes at base position 1456 of the UGT1A cDNA or 1459 of
      the UGT1D cDNA. These three mutations result in changes of glycine to arginine
      and of tyrosine to aspartic acid at amino acid positions 71 and 486 of the UGT1A
      protein, and of leucine to proline and of tyrosine to aspartic acid at amino acid
      positions 132 and 487 of the UGT1D protein, respectively. Our patient was
      homozygous for all defects and his parents and elder brother were heterozygous
      for all defective alleles. The findings suggest that the CN Type II is inherited
      as an autosomal recessive trait.

PMID- 8280140
TI  - Marrow adipocytes regulate growth and differentiation of osteoblasts.
AB  - Conditioned media (CM) from various marrow subpopulations (MBA series) were
      examined for their effects on growth and maturation of marrow-derived
      osteoblastic cells, MBA-15. CM harvested from a stromal adipocytes, 14F1.1,
      stimulated cell growth, collagen but not non-collagenous proteins synthesized by
      MBA-15 cells. Alkaline phosphatase activity was inhibited under the same culture
      conditions. These results were associated with morphological changes, i.e., the
      large cuboidal MBA-15 cells acquired a fibroblast-like appearance. Exposure of
      MBA-15 cells to known growth factors: BMP-2, TGF beta, IGF-I and PDGF or combined
      with 14F1.1 CM resulted in a dominant effect of the latter. This may imply that
      marrow adipocytes produce factor/s that participate in the stromal regulation of
      osteoblastic functions.

PMID- 8280141
TI  - Bovine articular chondrocytes do not undergo hypertrophy when cultured in the
      presence of serum and osteogenic protein-1.
AB  - Osteogenic protein-1 (hOP-1, BMP-7) is a member of the transforming growth factor
      beta superfamily. We have recently shown that hOP-1 induces and promotes
      maturation and hypertrophy of chick sternal chondrocytes, cultured in monolayer
      or suspension in the presence or absence of serum. In the present study we
      demonstrate that bovine articular chondrocytes, grown for up to 5 weeks in the
      presence of 0.5% or 10% serum in combination with 30 ng/ml hOP-1, do not undergo
      hypertrophy, as determined by cell size, the absence of type X collagen
      expression and synthesis, and of alkaline phosphatase activity. Treatment with
      hOP-1 (30 ng/ml) resulted in increased matrix synthesis as measured by
      [35S]sulfate incorporation and by collagen type II synthesis and expression,
      without influencing cell proliferation. These data suggest that primary mammalian
      articular chondrocytes are not able to undergo hypertrophy in conditions
      previously shown to be permissive for hypertrophy of both chick sternal and chick
      articular chondrocytes.

PMID- 8280142
TI  - Assembly of glucocorticoid receptor and c-JUN homodimer on the promoter of mouse
      mammary tumor virus-long terminal repeat is influenced by order of addition.
AB  - Interactions between the glucocorticoid receptor (GR) and c-Jun/c-Jun homodimer
      (JUN) on the promoter DNA of mouse mammary tumor virus-long terminal repeat (MMTV
      LTR) are reported here using the electrophoretic mobility shift assay (EMSA).
      Both GR and JUN are capable of independently binding to their respective response
      elements, including glucocorticoid response element (GRE) and phorbol ester
      response element (TRE), on MMTV-LTR promoter. The protein-DNA complex, assembled
      by pre-incubating JUN and DNA before the addition of GR, migrates slower
      (supershift) on gel electrophoresis than do the complexes formed by the other
      orders of addition. The formation of the supershifted complex is GR and JUN dose
      dependent. The supershift is not detected with the cleaved fragments of MMTV-LTR
      promoter that separate GRE from TRE, indicating that the integrity of the
      promoter and possibly the spacing between GRE and TRE are important. The
      interaction of GR and JUN on the MMTV-LTR promoter appears to be more complex
      than simple protein-protein interaction.

PMID- 8280143
TI  - Sodium nitroprusside promotes NAD+ labelling of a 116 kDa protein in NG108-15
      cell homogenates.
AB  - A 116 kDa protein in NG108-15 homogenates is labelled in the presence of
      [32P]NAD+. This protein was found to be poly(ADP-ribosyl)ated and appears to be a
      poly(ADP-ribosyl)transferase which has poly(ADP-ribosyl)ated itself. Sodium
      nitroprusside, an NO generating agent, also stimulates the labelling of this
      protein by [32P]NAD+, but this can only be seen in the presence of thymidine,
      which inhibits poly(ADP-ribosyl)transferase activity. Sodium nitroprusside also
      stimulates the labelling of this protein by [3H-nicotinamide]NAD+, indicating
      that NO facilitates the formation of an adduct between this protein and NAD+. The
      insensitivity of the linkage between the protein and NAD+ to mercuric ions
      indicates that the adduct does not involve thiol groups.

PMID- 8280144
TI  - Microamperometric estimation of photosynthesis inhibition in a single algal
      protoplast.
AB  - The single-cell level inhibition of photosynthesis by some chemicals was
      investigated from the light-irradiation induced response of intracellular oxygen
      reduction current at an ultramicroelectrode inserted into a single algal
      protoplast. The addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), an
      electron-transport inhibitor, decreased a current peak appeared immediately after
      the light irradiation. The pI50 value (the negative decadic logarithm of the
      concentration needed for 50% inhibition) was determined from the change in
      response patterns and found to be 6.9 for DCMU. 2,4-Dichlorophenoxyacetic acid
      (2,4-D), an auxin herbicide, showed no effect on photosynthesis in the effective
      concentration range. 2,4-Dinitrophenol (DNP), a proton carrier, accelerated the
      oxygen production upon light irradiation.

PMID- 8280145
TI  - On the existence of scaling in DNA sequences.
AB  - A re-evaluation of the properties of the random walks generated from DNA
      sequences reveals that previously reported scaling (appropriate to either pure
      random walks or long-range correlations) cannot be justified. Thus our analysis
      cannot support the claim that different evolutionary categories exhibit different
      scaling.

PMID- 8280146
TI  - Immunoaffinity purification of an oxidase-activating cytosolic complex from
      bovine neutrophils.
AB  - An oxidase activating complex from the cytosol of bovine neutrophils was purified
      by immunoaffinity using a monoclonal antibody specific for the 67 kDa cytosolic
      factor of oxidase activation (p67) and assayed for production of superoxide O2-
      in a cell-free system. The complex comprised not only p67, but also the second
      cytosolic factor of 47 kDa (p47) in equivalent amounts. The p47-p67 complex
      showed a good oxidase activating potency when added to neutrophil membranes in
      the presence of GTP-gamma-S and arachidonic acid. A ras-related small G protein
      could not be immunodetected in the p47-p67 activating complex, indicating that
      the GTP required for oxidase activation in the cell free system bound to a
      protein that was either present in catalytic amounts in the cytosolic complex or
      present in sufficient amount in the membrane fraction.

PMID- 8280147
TI  - Ratio of dihydropyridine to ryanodine receptors in mammalian and frog twitch
      muscles in relation to the mechanical hypothesis of excitation-contraction
      coupling.
AB  - An indirect argument in favour of the mechanical hypothesis of excitation
      contraction (EC) coupling [Schneider & Chandler (1973) Nature 242, 244-246] is
      the fixed stoichiometry between the voltage-driven dihydropyridine receptor (DHP
      R) on the transverse tubule (TT) and the ryanodine-sensitive Ca2+ channel (RyR)
      of sarcoplasmic reticulum (SR) terminal cisternae (TC), based mainly on the
      structural arrangement described by Block et al. at junctional triads of toadfish
      swimbladder muscle [Block, B., et al. (1988) J. Cell Biol. 107, 2587-2600]. We
      calculated the overall DHP-R/RyR ratios for a wide variety of rabbit twitch
      muscles, as compared to fast- and slow-twitch muscles of the rat, and to frog
      sartorius, following quantification of high-affinity binding sites for tritiated
      PN200-110 and ryanodine. To this purpose, we carried out our binding measurements
      on both skeletal muscle membranes detached from myofibrils by extensive
      extraction with low-ionic strength medium, and on the myofibrillar residue
      containing a proportion of binding sites. Our results expressed per gram of
      muscle allow the following main conclusions: i) The overall DHP-R/RyR ratio is
      approximately 2 in both fast-twitch and slow-twitch muscle of the rabbit,
      implying that most, if not all, Ca(2+)-channels at junctional triads are
      stoichiometrically associated with the voltage sensor; in agreement with Block's
      model; ii) There is a major inconsistency in these values, rather than in the
      absolute values of RyR sites, on side by side comparison of fast-twitch and of
      slow-twitch muscles of the rabbit and rat, in that the DHP-R/RyR ratio is
      invariably lower for the rat, i.e., only about 1.2. Since the absolute values of
      DHP-R sites, according to our calculations, agree well with those obtained for
      the same muscles by Lamb & Walsh [(1987) J. Physiol. 393, 595-617], it seems
      improbable that they were underestimated. On the assumption that there is a fixed
      stoichiometry between DHP-R and RyR at the junctional contact area between TT and
      TC, the relatively large excess of RyR sites in the rat, expressed per g. muscle,
      should be attributed to the presence of a proportion of Ca(2+)-channels that are
      located outside this area, i.e., are extrajunctional [Dulhunty, A., et al. (1992)
      Proc. R. Soc. Lond. (B) 247, 69-75].(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8280148
TI  - Cloning and in situ hybridization of type 2A and 2B rat skeletal muscle myosin
      tail region: implications for filament assembly.
AB  - Changes in fast myosin expression play a critical role in skeletal muscle
      adaptation. Two fast myosin isoforms, type 2A and type 2B, are commonly expressed
      by fast muscle fibers but their sequences have not been determined to allow mRNA
      expression studies. A complete set of rat skeletal muscle myosins was amplified
      by PCR of cDNAs derived from skeletal muscle mRNA, cloned in a TA cloning vector,
      and sequenced. Specificity was demonstrated by in situ hybridization against
      skeletal muscle and myosin protein identification using monoclonal antibodies.
      Two novel sequences were cloned: A type 2A myosin which consisted of a 642 bp
      segment from the 3' end and a type 2B myosin which consisted of a 624 bp segment
      also from the 3' end. This region encodes that portion of the myosin molecule
      implicated in the control of filament assembly. The two fast myosins showed 88%
      homology in the open reading frame and 95% homology at the amino acid level.
      Based on this homology, it is unlikely that selective myosin filament assembly
      occurs during muscle fiber type transformation between type 2A and 2B.

PMID- 8280149
TI  - Mitogenic stimulation of HeLa cells increases the activity of the anoxic stress
      protein, LDH 6/k: suppression by queuine.
AB  - Mitogenic stimulation of quiescent mammalian cells triggers an array of early
      events crucial for cell cycle progression. Here we show that the activity of the
      anoxic stress protein, lactate dehydrogenase 6/k, transiently increased after
      mitogenic stimulation of serum-starved HeLa cells. Regulation of lactate
      dehydrogenase 6/k activity in early G1 depended on the activity of a receptor
      tyrosine kinase and on protein and mRNA synthesis, but did not involve protein
      kinase C. The guanine analog, queuine, an ubiquitously occurring tRNA base of
      bacterial origin, suppressed the mitogen-induced protein synthesis and also the
      transient increase in lactate dehydrogenase 6/k activity. The results suggest
      that queuine relieves hypoxic stress resulting from mitogenic stimulation by
      suppressing protein synthesis during G0/G1 transition.

PMID- 8280150
TI  - Endotoxin protects the gastric mucosa against ulcerogenic stimuli.
AB  - It is well-documented that large amounts of endotoxin produce hemorrhagic mucosal
      lesions in the stomach. To determine whether endotoxin, when injected at small
      doses, similarly exerts ulcerogenic actions, endotoxin (0.4-40 micrograms/kg) was
      injected into 24 hr-fasted rats. These small doses of endotoxin did not affect
      the integrity of the gastric mucosa. Unexpectedly, however, pretreatment with
      these minute amounts of endotoxin protected the gastric mucosa against various
      ulcerogenic stimuli such as stress, nonsteroidal anti-inflammatory drugs and
      ethanol. The anti-ulcer actions of endotoxin were not observed in endotoxin
      insensitive animals (C3H/HeJ mice), thereby suggesting that endogenous cytokines
      such as interleukin-1 may mediate these protective actions. These findings stand
      in contrast to the toxic effect of endotoxin as an ulcerogen and indicate that
      endotoxin, albeit its term "toxin," may have a beneficial effect for the host.

PMID- 8280151
TI  - Purification and characterization of a strong fibrinolytic enzyme (nattokinase)
      in the vegetable cheese natto, a popular soybean fermented food in Japan.
AB  - A strong fibrinolytic enzyme (nattokinase) was purified from the vegetable cheese
      natto. Nattokinase was extracted from natto with saline and isolated by
      sequential use of hydrophobic chromatography on Butyl-Toyopearl, ion-exchange
      chromatography on CM-Toyopearl, and gel-filtration on Sephadex G-50. The isolated
      protein gave a single sharp band on SDS-PAGE either before or after reduction.
      The sequence, as determined by automated Edman degradation of the uncleaved
      molecule and its enzymatically derived peptide, consisted of a total 275 amino
      acid residues (M.W = 27,728) and exhibited a high homology with the subtilisins.
      The purified nattokinase digested not only fibrin but also several synthetic
      substrates. Among the synthetic substrates, the most sensitive substrate was Suc
      Ala-Ala-Pro-Phe-pNA for subtilisin. PMSF inhibited both the fibrinolytic activity
      and the amidolytic activity. The results indicate that nattokinase is a
      subtilisin-like serine protease.

PMID- 8280152
TI  - ATP-driven transhydrogenation and ionization of water in a reconstituted
      glyceraldehyde-3-phosphate dehydrogenases (phosphorylating and non
      phosphorylating) model system.
AB  - In an unbuffered medium, an intense acidification occurs during the oxidation of
      D-glyceraldehyde-3-phosphate (G3P) to 3-phospho-D-glycerate (PGA) catalyzed by
      NADP(+)-specific non-phosphorylating G3P dehydrogenase, an enzyme that
      photosynthetic eukaryotic cells contain exclusively in their cytosol. The true
      enzymatic character of this proton release is the consequence of the following
      redox/acid-base reaction: G3P + NADP+ + H2O-->PGA + NADPH + 2H+. When the well
      established ATP-dependent reduction of PGA to G3P, catalyzed by PGA kinase and
      NAD(+)-specific phosphorylating G3P dehydrogenase, was coupled through the
      intermediate G3P to the above reverse oxidation reaction, a transient
      alkalinization of the medium followed by its acidification accompanied
      transhydrogenation from NADH to NADP+. The significance of the observed
      endergonic transhydrogenation and ionization of water at the expense of the
      chemical energy of ATP in this reconstituted enzyme system as well as its
      relevance for the export of reducing power (H-) across the chloroplast membrane
      and the maintenance of the pH gradient that exists between the stroma and the
      cytosol are discussed.

PMID- 8280153
TI  - Changes in in vivo protein-DNA interactions occur at the c-myc P2 promoter during
      differentiation.
AB  - Down regulation of the c-myc gene is a prerequisite for the differentiation of a
      number of cell types. Studies have shown that two mechanisms of inactivation are
      involved in c-myc repression: a block of the elongation of RNA polymerase
      followed by transcriptional inactivation mediated through promoter sequences. In
      this study DMS in vivo footprinting was performed on the P2 promoter region of c
      myc in differentiated and undifferentiated HL60 cells. A differentiation-specific
      footprint was observed at G residues immediately upstream of the TATA box. This
      observation occurred only in cells differentiated for 48 hours or more and hence
      is likely to be involved in the repression of c-myc by promoter inactivation.

PMID- 8280154
TI  - Extra-hepatic transcription of plasma prekallikrein gene in human and rat
      tissues.
AB  - The expression of plasma prekallikrein (PPK) mRNA has been investigated applying
      reverse transcription, followed by polymerase chain reaction, of mRNA (RT-PCR) in
      various human and rat tissues. PPK gene transcripts were detected in liver and
      kidney in both species and, in addition, in human adrenal gland and placenta. No
      PPK mRNA was identified in rat adrenal gland, heart, aorta, lung, brain cortex
      and medulla, hypothalamus, and uterus. These results show that PPK gene
      expression is not restricted to the liver.

PMID- 8280155
TI  - Osmotic stress is the main determinant of the diameter of the actin filament.
AB  - The diameter of the actin filament is influenced by osmotic stress, being 9.0 nm
      at 1 x 10(5) dynes/cm2 and 6.8 nm at 9.00 x 10(6) dynes/cm2. At 1.81 x 10(5)
      dynes/cm2, the protein osmotic pressure in frog muscle, the diameter is 7.95 nm.
      The diameter of the tropomyosin-decorated actin filament is also influenced by
      osmotic stress even though, at the low pressures (up to 2 x 10(5) dynes/cm2), the
      decorated filament is significantly more resistant to compression than the
      undecorated actin filament.

PMID- 8280156
TI  - Multiple mismatch annealing: basis for random amplified polymorphic DNA
      fingerprinting.
AB  - In order to investigate the possible mechanism underlying the random amplified
      polymorphic DNA (RAPD) fingerprinting, we examined the origin and the nucleotide
      sequences of RAPD bands. Our data suggest that a number of sites in the genome
      are flanked by perfect or imperfect invert repeats, which permit multiple
      mismatch-annealing to occur between the single primer and the template DNA and
      eventually lead to the exponential amplification of the encompassing DNA
      segments.

PMID- 8280157
TI  - Modulation of POMC expression in human neuroectodermal cells.
AB  - Neuroblastoma cell lines have been reported to contain two proopiomelanocortin
      (POMC) mRNA transcripts. We have now shown by immunocytochemistry and
      radioimmunoassay (RIA) that a number of neuroectodermally derived cell lines
      contain immunoreactive beta-endorphin although cell concentrations were not
      characteristic of any tumour type. To explore further the functional significance
      of beta-endorphin expression, we analysed neuroblastoma cell lines having
      intermediate (I), substrate adherent (S) and neuronal (N) phenotypes. No
      differences in cell beta-endorphin content were detected. However, the expression
      of POMC mRNA and of immunoreactive beta-endorphin was reduced within a few hours
      of treatment of these cell lines with retinoic acid. Culture of the cell lines in
      the presence of beta-endorphin resulted in small but significant increases in
      growth. Although the POMC gene is in the same chromosomal segment as N-myc, which
      is normally amplified in neuroblastoma, no corresponding amplification of POMC
      could be demonstrated. The data suggest that POMC gene products may contribute to
      the autocrine/paracrine growth of neuroectodermal tumours.

PMID- 8280158
TI  - Apolipoprotein B mRNA editing in vitro is a zinc-dependent process.
AB  - Apolipoprotein B mRNA editing involves the conversion of a cytidine at nucleotide
      6666 to a uridine, thereby creating a translational stop codon from a glutamine
      codon. Recent evidence suggest that a cytidine deaminase is responsible for
      catalyzing the C to U conversion. All known nucleotide deaminases require zinc as
      part of their catalytic domain. Utilizing the selective chelator for zinc, 1,10
      penanthroline, we demonstrate that in vitro editing activity in rat liver
      extracts is zinc dependent. These data, taken together with recent reports,
      strongly support a role for a cytidine deaminase and nucleotide conversion as the
      catalytic mechanism for apoB mRNA editing.

PMID- 8280159
TI  - Production and properties of recombinant C3-type phosphoenolpyruvate carboxylase
      from Sorghum vulgare: in vitro phosphorylation by leaf and root PyrPC protein
      serine kinases.
AB  - In this work, the C3-type form of Sorghum phosphoenolpyruvate carboxylase (PyrPC)
      was produced in PyrPC-deficient strains of Escherichia coli transformed by a
      plasmid bearing the corresponding full-length cDNA (CPR1). The full-sized protein
      was purified to homogeneity by immunoaffinity chromatography. Some functional and
      regulatory properties were described; notably, the immunopurified PyrPC could be
      phosphorylated in reconstituted assay by 1) both a mammalian PKA and the PyrPC
      protein serine kinase purified from Sorghum leaves and 2) a novel protein kinase
      affinity-purified from Sorghum roots. In all cases phosphorylation was
      accompanied by a marked reduction in its malate sensitivity.

PMID- 8280160
TI  - Tumor necrosis factor upregulates interleukin-4 receptors on murine sarcoma
      cells.
AB  - We have previously shown that murine solid tumor cells express high affinity IL-4
      receptors (IL-4R) which are internalized after binding to ligand. In the present
      study, we have examined the regulation of IL-4R by TNF. We demonstrate that TNF
      upregulated the expression of IL-4R on murine MCA-106 sarcoma cells. Maximum
      upregulation of IL-4R surface expression occurred after 24 h, whereas, maximum
      elevation in IL-4R mRNA levels was observed after only 4 hours of TNF treatment.
      This increase in mRNA levels for IL-4R occurred in a dose dependent manner. As
      little as 0.83 ng/ml of TNF significantly upregulated mRNA levels, whereas
      maximum effect was obtained with 83 ng/ml TNF. IL-4 receptor density was
      increased in response to TNF, no effect on IL-4R affinity was observed.
      Cycloheximide and Actinomycin D treatment decreased the surface expression of IL
      4R by 50% in about 2 h and 7 h, respectively, in both TNF treated and untreated
      cells indicating the half life for the IL-4R protein expression. These studies
      may help understand the mechanism of cytokine interaction on tumor cells.

PMID- 8280161
TI  - The effects of nitric oxide on chondrocytes and lymphocytes.
AB  - ConcanavalinA (ConA)-activated lymphocytes markedly induced the production of
      nitric oxide from chondrocytes. The nitric oxide significantly inhibited the
      proliferation of both the chondrocytes themselves and the lymphocytes. When
      culture supernatant from ConA-activated lymphocytes was added to culture of
      chondrocytes, a large amount of nitric oxide was produced. NG-monomethyl-L
      arginine (MMA) significantly eliminated both the production of nitric oxide and
      the inhibition of chondrocyte and lymphocyte proliferation. Furthermore, when MMA
      was added to the mixed culture of chondrocytes and lymphocytes with ConA, their
      proliferation was markedly enhanced compared with individual summation. These
      results indicate that chondrocytes produce not only nitric oxide but also a
      lymphocyte stimulating factor, the effects of which are, however, usually masked
      by the nitric oxide.

PMID- 8280162
TI  - Structural repeats in cyclosporin A.
AB  - The conformation of various dipeptides of free and cyclophilin A-bound
      cyclosporin A were compared. Cyclosporin A was shown to contain in both states
      conformationally duplicated fragments in the putative binding sites for
      cyclophilin A and phosphatase calcineurin.

PMID- 8280163
TI  - Transforming growth factor-beta up-regulates the gene expression of the human
      platelet-activating factor receptor in monocytic and B cell lines.
AB  - Platelet-activating factor is a potent phospholipid mediator which produces a
      wide range of biological responses by binding to a specific, high-affinity
      receptor on the target cell surface. Platelet-activating factor has been shown to
      have a very important pro-inflammatory role while the cytokine transforming
      growth factor-beta, also known for its diverse and potent effects, can act as
      both a pro- and anti-inflammatory agent. To ascertain whether transforming growth
      factor-beta could modulate the expression of the human platelet-activating factor
      receptor, different cell types were stimulated with this cytokine and the effect
      determined by Northern blot analysis and Ca2+ influx studies. The results
      demonstrate that transforming growth factor-beta induces the expression of the
      platelet-activating factor receptor in monocytic and B cell lines and indicate
      that transforming growth factor-beta could play a role in the modulation of the
      inflammatory response by up-regulating the expression of the platelet-activating
      factor receptor.

PMID- 8280164
TI  - Effects of transforming growth factor beta and interleukin-1 beta on expression
      of cyclooxygenase 1 and 2 and phospholipase A2 mRNA in lung fibroblasts and
      endothelial cells in culture.
AB  - Experiments were conducted to determine the roles of the rate limiting enzymes,
      cyclooxygenase 1 and 2 (COX1 and COX2) and cytoplasmic phospholipase A2 (PLA2),
      in transforming growth factor beta (TGF-beta) and interleukin-1 (IL-1 beta)
      activated prostaglandin synthesis. Results show that TGF-beta increases steady
      state levels of COX1 mRNA in both human embryo lung fibroblasts (IMR90) and calf
      pulmonary artery endothelial cells (BPAEC). Temporal experiments show that TGF
      beta increases, within 2hrs, a 5.5kb COX1 in IMR90 and the 2.7kb COX1 mRNA in
      BPAEC. IL-1 beta increases COX1 mRNA only in IMR-90, not BPAEC. COX2 mRNA, under
      basal conditions, is not detected in BPAEC and is expressed only marginally in
      IMR90. TGF-beta or IL-1 beta have no effect on expression of COX2 gene in either
      cell type. IL-1 beta increases steady state levels of PLA2 mRNA in both IMR90 and
      BPAEC while TGF-beta increases expression of the PLA2 gene only in BPAEC. Time
      experiments with TGF-beta show induction of PLA2 mRNA within 1hr, peaking at
      4hrs. PG synthesis in response to the cytokines was determined in IMR90 and BPAEC
      to further assess the significance of the above results. TGF-beta increases the
      synthesis of prostacyclin in BPAEC in a time related fashion peaking at 8hrs at
      13 fold above basal. To focus on the action of COX1 and bypass the action of
      PLA2, exogenous arachidonic acid was used as substrate for PG synthesis. In these
      experiments IL-1 beta increases PGE2 synthesis 8 fold in IMR90 while IL-1 beta
      and TGF-beta added simultaneously increases PGE2 synthesis 25 fold. These results
      in sum illustrate that the cytokines, TGF-beta and IL-1 beta, regulate both COX1
      and PLA2 mRNA levels. Furthermore, this regulation appears coordinated to bring
      about elevation of prostaglandin synthesis.

PMID- 8280165
TI  - Expression of ionotropic glutamate receptor genes by P19 embryonal carcinoma
      cells.
AB  - P19 embryonal carcinoma cells can be induced to differentiate into neuron-like
      cells by retinoic acid. P19 neurons were recently shown to express both NMDA and
      non-NMDA type glutamate receptor-mediated currents and be susceptible to
      glutamate excitotoxicity. In this study, we used RT-PCR to survey differentiated
      P19 cultures for glutamate receptor transcript expression. The following
      transcripts were detected: at least one member of the GluR1-4 family, GluR5,
      GluR6, GluR7, KA1, KA2, NMDAR1, and NMDAR2B. Nuclease protection assays revealed
      a large quantitative induction of GluR6 transcripts following retinoic acid
      treatment. Inotropic glutamate receptors are a fundamental and major feature of
      CNS neurons which are not expressed by the cell lines commonly used as
      experimental models for mammalian neurons. The present results show that P19
      cells express multiple genes involved in glutamate receptor biology. Since the
      stem cells can be manipulated genetically, the system has the basic requirements
      for analyzing mechanisms involved in glutamate receptor gene expression.

PMID- 8280166
TI  - An immunization method for generation of high affinity antisera against glucose
      transporters useful in immunohistochemistry.
AB  - Antipeptide antisera from unique amino acid sequences of proteins, predicted from
      their cDNA, are useful to study cellular distribution of these proteins, but such
      peptides often are poorly immunogenic. We describe a secondary immunization
      method with repeated intravenous administration of KLH-conjugated peptides to
      boost the immune response rapidly and transiently as high as 60-fold to peptides
      of low immunogenicity (glucose transporters, GLUT3 and GLUT4). Such antisera are
      suitable for immunocytochemistry with excellent anatomic detail. This method may
      be generally useful as it is reproducible and can yield progressive titer
      increases when repeated.

PMID- 8280167
TI  - Deoxycytidine and 2',3'-dideoxycytidine metabolism in human monocyte-derived
      macrophages. A study of both anabolic and catabolic pathways.
AB  - In the present study we have explored the catabolism of dCyd and 2',3'
      dideoxycytidine (ddC) in mature monocyte-derived macrophages (M/M) and focused on
      its relation to the accumulation of intracellular anabolites. We found that dCyd
      catabolism in M/M was significant in 1-week old cultures (15% of 0.5 microM dCyd,
      0.5 nmole/million cells, catabolized within one hour of incubation) and further
      increased in more mature 3-week and 5-week old cultures (> 85% catabolized within
      one hour). Dihydrouracil (DHU) was irreversibly formed as end product of the dCyd
      catabolism, with dUrd and Ura as intermediate metabolites. Intracellularly, dCyd
      nucleotides were detected up to three hours of incubation, with dCTP maintained
      at steady levels between one and three hours. However, after twelve hours of
      incubation DHU was the only detectable intracellular as well as extracellular
      metabolite. In contrast to what was observed with dCyd, we found that ddC was
      resistant to catabolism, with no detectable catabolites formed within twenty-four
      hours of incubation. Therefore ddC anabolism was unopposed by catabolic pathways
      and consequently intracellular anabolites of ddC accumulated throughout twenty
      four hours of incubation. Based on these results, we propose that lack (or
      inhibition) of catabolism is at least as important as efficient anabolic
      phosphorylation for obtaining therapeutic effects of pyrimidine nucleoside
      analogs.

PMID- 8280168
TI  - Increased levels of sequence-specific DNA-binding proteins in human
      cytomegalovirus-infected cells.
AB  - Increased levels of active sequence-specific DNA-binding proteins, AP-1, CRE/B,
      and NF kappa B were observed in nuclear lysates of human cytomegalovirus-infected
      cells from 15 min postinfection. The activation of these cellular factors did not
      require infectious virus or de novo viral protein synthesis, but their abundance
      was significantly reduced by inhibitors of protein kinase C and/or A. These data
      suggest that formation of these transcription factors resulted from the virus
      cell membrane interaction and/or through the action of virion structural proteins
      on cytoplasmic forms of these cellular factors.

PMID- 8280169
TI  - Expression of human placental cytochrome P450 aromatase (CYP19) cDNA in insect
      cells using a luciferase based baculovirus vector.
AB  - The cDNA encoding human placental cytochrome P450 aromatase (CYP19) was expressed
      in Spodoptera frugiperda (Sf9) insect cells using the baculovirus expression
      vector system. The recombinant protein product was characterized by Northern and
      Western blot analyses as well as by direct measurement of aromatase activity. The
      expressed enzyme proved to be both catalytically active in the presence of P450
      reductase and immunologically reactive with polyclonal antibodies raised against
      human placental aromatase. The activity of aromatase increased 10% after the
      addition of 0.1 microgram/ml hemin chloride to the culture medium. However, the
      level of aromatase protein decreased considerably when the concentration of hemin
      chloride reached 10 micrograms/ml indicating that hemin chloride has toxic
      effects on the lepidopteran insect cell line. In conclusion, the baculovirus
      system is suitable for high level expression of functional human placental CYP19.

PMID- 8280170
TI  - Complete amino acid sequence of biliverdin-IX beta reductase from human liver.
AB  - The amino acid sequence of biliverdin-IX beta reductase (EC1.3.1.24) from human
      liver was determined by automated Edman degradation of peptides generated by
      enzymatic and chemical cleavages. The enzyme was a single polypeptide chain of
      204 amino acid residues, and its amino acid sequence had no significant homology
      to that of rat liver biliverdin-IX alpha reductase. Biliverdin-IX alpha reductase
      from human liver had intense homology to the rat enzyme. Cysteinyl residues are
      essential for the enzymatic activity of biliverdin-IX alpha, but nonessential for
      that of biliverdin-IX beta reductase. The results strongly indicate that the two
      enzymes, biliverdin-IX alpha reductase and biliverdin-IX beta reductase, are
      distinct in enzymatic action mechanisms as well as ancient origins of gene.

PMID- 8280171
TI  - Molecular cloning and identification of two types of hamster cyclin-dependent
      kinases: cdk2 and cdk2L.
AB  - We isolated two types of hamster cyclin-dependent kinase 2 (cdk2) cDNAs from
      BHK21 cells derived from Golden hamsters. One type of cdk2 (cdk2hm) encodes the
      32 kDa protein consisting of 298 predicted amino acids and shows strong homology
      to the cdk2 cDNAs of humans and Xenopus. The other cdk2 (cdk2Lhm) encodes the 38
      kDa protein containing the insertion of 48 amino acids in the cdk2hm protein.
      Immunoblotting analysis suggested that these two types of cdk2 protein exist in
      mammalian cells. The cdk2hm has the activity of protein kinase, while the cdk2Lhm
      does not, however, both bind with cyclin E.

PMID- 8280172
TI  - Recombinant thyrotropin stimulates cAMP formation in CHO-K1 cells expressing
      recombinant chorionic gonadotropin receptor.
AB  - Using CHO-K1 cells expressing rat thyrotropin-receptor (CHO-rTSH-R cells) or rat
      chorionic gonadotropin-receptor (CHO-rCG-R cells), we have examined their
      reactivity or cross-reactivity to recombinant human thyrotropin (TSH) or human
      chorionic gonadotropin (hCG). TSH stimulated cAMP formation in CHO-rTSH-R cells
      dose-dependently, and the maximum response was obtained at 1 mIU/ml. hCG also
      increased cAMP in the cells from 10(4) mIU/ml, and the maximum stimulation was
      observed at 10(6) mIU/ml. 10(7) mIU of hCG had the same potency with 1 mIU of TSH
      to rTSH-R. On the other hand, 10(-1) mIU/ml of hCG increased cAMP content in CHO
      rCG-R cells and reached the maximum level at 10(2) mIU/ml. TSH also showed the
      stimulatory activity to CHO-rCG-R cells. It increased cAMP formation in CHO-rCG-R
      cells dose-dependently from 10 mIU/ml to 10(3) mIU/ml. Thirty mIU of TSH was
      calculated to be equivalent to 1 mIU of hCG to CG-R. These results indicate that
      TSH and hCG cross-react each other with rTSH-R or rCG-R.

PMID- 8280173
TI  - Physico-chemical modeling of the role of free radicals in photodynamic therapy.
      II. Interactions of ground state sensitizers with free radicals studied by
      chemiluminescence spectrometry.
AB  - Chemiluminescence (CL) studies of the interaction between ground state
      hematoporphyrin photosensitizer (Hp) and peroxy radicals generated by the
      initiated oxidation of ethylbenzene at 60-80 degrees C revealed, that Hp is a
      singlet-singlet acceptor similarly to 9,10-diphenylanthracene. Furthermore, the
      fast decrease in the CL signal in the presence of Hp indicated that its
      consumption also took place due to chemical transformation, presumably by the
      attack of peroxy radicals on Hp. The rate constant of this attack has been
      calculated and it supports the view that such interaction can lead to an
      essential contribution to the bleaching processes in vivo.

PMID- 8280174
TI  - Studies of vanadyl sulfate as a glucose-lowering agent in STZ-diabetic rats.
AB  - To study the effect of vanadium (V) intake on blood glucose lowering, tissue V
      concentrations, glutathione reductase (GR) activity, and plasma trace metal
      concentrations, streptozotocin(STZ)-diabetic rats were treated with vanadyl
      sulfate (VS) (0.5-1.2 g/l in the drinking water) for up to 12 weeks. Kidney and
      plasma V concentrations were positively correlated with V intake. Kidney GR
      activities were not affected by VS treatment nor were plasma cobalt, molybdenum,
      manganese or lithium concentrations. Individual V intakes were dependent upon
      severity of diabetes, with more hyperglycemic rats consuming greater quantities
      of VS solution. A diminished effect on glucose lowering of VS above 1 g/l was
      noted.

PMID- 8280175
TI  - Systemic production of interleukin-6 following acute inflammation.
AB  - The present study was designed to evaluate whether IL-6 is produced locally or
      systemically following acute inflammation. Full-thickness scale burns were made
      on rats. Serum IL-6 levels (SIL-6) showed a constant time-dependent change with a
      single peak 6 hours after the burn. SIL-6 elevation was correlated with the ratio
      of burn area to total body surface area. The liver, spleen, lymph node and skin
      harvested after the burn secreted significantly higher amounts of IL-6 after
      tissue culture when compared with those taken from sham rats. The venous serum
      drainage from the burn site induced significantly higher IL-6 production of
      splenocytes than the arterial and control venous sera. In conclusion, IL-6
      production is rapidly and systemically triggered by a humoral factor following
      acute inflammation in vivo, resulting in constant kinetics for SIL-6.

PMID- 8280176
TI  - Okadaic acid inhibits dephosphorylation of cytoplasmic p53 during lymphocyte
      activation.
AB  - A competition radioimmunoassay specific for conserved Domain V of p53 revealed
      that Domain V was masked in highly phosphorylated cytosolic p53 of resting T
      lymphocytes and unmasked through dephosphorylation during lymphocyte activation.
      Phosphatase type 2A was shown to act upon immunopurified p53 in a manner that
      increased the immunoreactivity of the molecule in the Domain V RIA. Treatments of
      T cells with okadaic acid (1nM) prior to addition of Concanavalin-A/serum
      inhibited completely the dephosphorylation of cytosolic p53 observed to occur
      within 10-20min of stimulation. Brief exposure of T cells to okadaic acid during
      the first hour of activation by mitogens produced increased rates of cellular
      proliferation. Sustained inhibition of the dephosphorylation of cytoplasmic p53
      in cells undergoing mitogenic stimulation may affect adversely the ability of p53
      to exert its anti-proliferative effect and could contribute to unregulated cell
      growth.

PMID- 8280177
TI  - N E. coli, inducible DNA repair is error-prone with regard to lethality.
AB  - The umuC gene is a member of the inducible SOS repair network in E. coli. The
      experiments reported here indicate that the product of the umuC locus can make
      lethal mistakes during its normal repair function. Such "lethal repair" may be a
      major factor in establishing a cell's sensitivity to radiation.

PMID- 8280178
TI  - Phosphorylation of Ca2+/calmodulin-dependent protein kinase V and regulation of
      its activity.
AB  - Autophosphorylation of Ca2+/calmodulin-dependent protein kinase V (CaM kinase V)
      resulted in a drastic potentiation of the Ca2+/calmodulin-dependent activity, but
      Ca2+/calmodulin-independent activity was not generated. The rate of
      autophosphorylation increased with increases in the enzyme concentration, thereby
      suggesting intermolecular reactions. In the course of these investigations,
      another factor by which CaM kinase V is also phosphorylated and activated became
      evident. The addition of EGTA blocked CaM kinase V phosphorylation. The
      autophosphorylated CaM kinase V was not phosphorylated by the activator. These
      observations suggest that the activation factor is a CaM kinase which
      phosphorylates CaM kinase V at the autophosphorylation site, thereby potentiating
      the enzymatic activity.

PMID- 8280179
TI  - Genomic cloning, heterologous expression and pharmacological characterization of
      a human histamine H1 receptor.
AB  - A human histamine H1 receptor gene lacking introns was isolated by screening a
      human genomic library with a bovine histamine H1 receptor probe. The deduced
      protein of 487 amino acids showed characteristic properties of G-protein-coupled
      receptors. The coding region was subcloned into the expression vector pSVL
      (Pharmacia), and the resulting construct transfected into COS-7 cells. Binding
      studies with [3H]pyrilamine on membranes from transfected cells revealed
      saturable specific binding with a KD of 1.2 nM and a Bmax of 3400 fmol/mg
      protein. Binding affinities of histamine and known histamine antagonists were
      similar to those for histamine H1 receptors in guinea-pig cerebellum. In
      transfected COS-7 cells, histamine induced inositol phosphate formation, that was
      inhibitable by pyrilamine.

PMID- 8280180
TI  - The effects of saturated fat and n-6 polyunsaturated fat on postprandial lipemia
      and hemostatic activity.
AB  - The effect of different fat loads on postprandial lipemia and hemostatic activity
      was examined in 10 middle-aged men using 3 different meals. One meal was rich in
      saturated fatty acids (cream), the other rich in n-6 polyunsaturated fatty acids
      (sunflower oil) and the third was fat-free containing only carbohydrates.
      Lipoprotein lipids and hemostatic parameters were measured during fasting and 2,
      4, 6 and 8 h after the test meal. In fasting samples, several hemostatic
      parameters were significantly associated with lipoprotein lipids. Most notable
      were the strong associations of fibrinolysis parameters tissue plasminogen
      activator antigen and plasminogen activator inhibitor activity (PAI-1) with total
      and very low density lipoprotein (VLDL) triglycerides. During lipemia, the
      associations were approximately similar or slightly weaker than in the fasting
      state. Both fat loads resulted in similar postprandial lipid responses: VLDL and
      high density lipoprotein (HDL) triglycerides reached maximum at 4 h after the
      meal. VLDL cholesterol also increased 4 and 6 h after the fat loads. HDL3
      cholesterol declined after the fatty meals but no change was observed in the HDL2
      fraction. The fat-free meal gave no significant lipid changes during the time
      course studied. Factor VII activity (F VII:C) increased 6 and 8 h after the fatty
      meals, whereas a decrease was observed after the fat-free meal. The changes (+/-
      S.D.) at 8 h after cream, sunflower oil and fat-free meal were 5.2 +/- 3.3, 3.3
      +/- 4.2 and -5.8 +/- 7.9 percentage points, respectively, and the effect of the
      meal on the changes was statistically significant (F (8,99) = 2.99, P = 0.0048).
      F VII antigen (F VII:Ag) tended to decline during the day but there was no
      difference between the meals. Factor VIII activity (F VIII:C) was highest after
      the polyunsaturated fat meal and lowest after the fat-free meal. PAI-1 declined
      during the day and the decline tended to be steepest after the fat-free morning
      meal. The effect of the meal on the changes in lipoprotein lipids and hemostatic
      factors varied significantly between individuals. In conclusion, postprandial
      lipemia after a single fatty meal was associated with procoagulatory change in F
      VII:C but there was no difference between saturated fat and n-6 polyunsaturated
      fat.

PMID- 8280181
TI  - Increased platelet-fibrinogen interaction in patients with hypercholesterolemia
      and hypertriglyceridemia.
AB  - Binding of fibrinogen to platelets washed from the blood of patients with
      hypercholesterolemia and hypertriglyceridemia (n = 25) and control donors (n =
      12) was compared. In addition, the content of platelet glycoprotein IIb was
      determined by radioimmunoassay. Fibrinogen was bound in significantly higher
      amounts (P < 0.02) to hyperlipidaemic platelets activated by ADP than to control
      ones (107,112 +/- 16,371 and 45,612 +/- 6495 molecules per platelet,
      respectively). The mean content of GPIIb was the same in hyperlipidaemic and in
      control platelets (2.06 +/- 0.16 and 1.94 +/- 0.21 micrograms/10(8) platelets,
      respectively). The amount of fibrinogen bound to the activated hyperlipidaemic
      platelets showed a positive correlation with total plasma cholesterol and LDL (r
      = 0.45 and 0.47, respectively) whereas a negative correlation with plasma HDL was
      found (r = -0.50). The increased expression of fibrinogen binding sites similar
      to that of hyperlipidaemic platelets could be produced by preincubation of normal
      platelets with palmitic acid. This was evidenced by a significant increase of
      fibrinogen binding sites in control platelets. This suggests that either
      palmitoylation of the receptor or microenvironment changes in the membrane lipid
      bilayer may be responsible for the enhanced platelet receptor capacity to bind
      fibrinogen.

PMID- 8280182
TI  - Lack of an association between serum vitamin E and myocardial infarction in a
      population with high vitamin E levels.
AB  - The antioxidant effects of vitamin E may protect low density lipoproteins from
      peroxidation and thus inhibit the development of arteriosclerosis. Inverse
      associations between vitamin E levels and coronary heart disease have been
      reported from cross-sectional and ecologic studies. In the population-based
      MONICA Augsburg cohort (2023 men, 1999 women, age 25-64 years at baseline in
      1984, 93% of whom were reexamined in 1987/88) we investigated the relationship
      between serum vitamin E concentrations and the risk of subsequent myocardial
      infarction (MI). Between 1984 and 1991, 46 cases of fatal and non-fatal
      myocardial infarction from this cohort were recruited for a nested case-control
      study. Four controls were sampled from the cohort for each case of MI with
      matching for age, sex, and total cholesterol. There were no marked differences
      between cases and their matched controls in the means of vitamin E concentrations
      (33.9 mumol/l vs. 32.8 mumol/l, P = 0.37) or in the mean vitamin E/total
      cholesterol ratios (4.89 mumol/mmol vs. 4.82 mumol/mmol, P = 0.75). The covariate
      adjusted relative risk (RR) for fatal plus non-fatal MI in the lowest tertile of
      vitamin E relative to the upper two tertiles was 0.72 (90% confidence interval:
      0.33-1.57). Likewise, for the lowest tertile of the ratio (vitamin E/total
      cholesterol) the RR was 0.81 (0.42-1.56). The association was not modified by
      history of previous coronary heart disease, fatality of MI, temporal distance of
      MI onset from vitamin E determinations, or season.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8280183
TI  - Elevated high density lipoprotein concentrations in heart transplant recipients
      are related to impaired plasma cholesteryl ester transfer and hepatic lipase
      activity.
AB  - Accelerated atherosclerosis is a major complication of heart transplantation, and
      is frequently associated with a dyslipoproteinemia characterized by a paradoxical
      increase in HDL-cholesterol concentration. To define this abnormality, the
      lipoprotein profiles of 25 heart transplant recipients (HTR) were analyzed and
      compared with those of 26 control subjects. HDL, as separated on the basis of
      density in 3 subfractions, were increased in concentration: HDL2: +51%, HDL3a:
      +29%, HDL3b: +32%. HDL2 and HDL3a displayed an enrichment in surface components,
      phospholipids, unesterified cholesterol and apo E, leading to an increased size
      compared with subfractions of similar density in the controls. The major steps of
      plasma HDL metabolism were investigated: cholesterol esterification (LCAT
      activity), cholesteryl ester transfer to apo B-containing lipoproteins (CETP) and
      the hepatic hydrolysis of HDL components (HL activity). We demonstrated a partial
      deficiency in CETP (-28%) and hepatic lipase (-36%) activities with normal LCAT
      activity. Correlations in total study population (HTR plus controls) evidenced
      negative associations between CETP activity and HDL3a concentrations and between
      HL activity and HDL2-cholesterol as a percent of total HDL-cholesterol.
      Therapeutic agents used in post transplantation treatment such as glucocorticoids
      and/or cyclosporine may be speculated thus to affect both CETP and HL activities
      and, by arresting the HDL cycle in a CE-saturated state, do decrease the
      efficiency of reverse cholesterol extraction at the site of the graft.

PMID- 8280184
TI  - Exogenous glucocorticoids increase macrophage secretion of apo E by cholesterol
      independent pathways.
AB  - Macrophage apo E synthesis and secretion has been previously demonstrated to be
      regulated by intracellular free cholesterol levels and is decreased by cytokines
      and other inflammatory stimuli associated with macrophage activation. In a recent
      study, the opposing effects of TGF beta and GM-CSF were reported with the former
      increasing and the latter decreasing apo E secretion and apo E mRNA levels. In an
      attempt to further understand the mechanisms by which TGF beta increased apo E
      expression in mouse peritoneal macrophages, the present study was performed to
      determine whether pharmacological agents could up-regulate apo E secretion by a
      mechanism independent of intracellular free cholesterol levels. Agents which
      resulted in increased apo E secretion were subdivided based on their effects on
      cAMP elevation. In addition to TGF beta, dexamethasone resulted in significant
      increases in apo E secretion. The 2-4-fold enhancement in apo E secretion by both
      TGF beta and dexamethasone occurred without concomitant changes in intracellular
      cAMP or free cholesterol. Other agents which increased apo E secretion included
      cholera toxin and 8-bromo-cAMP. While these agents did not affect intracellular
      cholesterol levels, cholera toxin did increase macrophage cAMP. The changes in
      apo E secretion by dexamethasone and 8-bromo-cAMP were associated with elevations
      in apo E mRNA. Dexamethasone-treated macrophages had 6-fold increases in apo E
      mRNA by 48 h when compared with control macrophages. Macrophages stimulated with
      8-bromo-cAMP for 48 h demonstrated a more modest but statistically significant (P
      < 0.001) 2.2-fold increase. Similar effects of dexamethasone, cholera toxin, TGF
      beta, and 8-bromo-cAMP on apo E secretion were also apparent in macrophage
      derived foam cells. In addition to increasing apo E secretion in macrophages and
      foam cells, dexamethasone and 8-bromo-cAMP inhibited the down-regulation of apo E
      secretion mediated by LPS and GM-CSF. Finally, the increased apo E secretion by
      exogenous glucocorticoids or TGF beta was not species specific as similar effects
      were observed in rabbit peritoneal macrophages. Therefore, while macrophage
      activation results in decreased apo E synthesis, macrophages exposed to anti
      inflammatory agents including dexamethasone, TGF beta, or following cAMP
      elevation demonstrate increased apo E secretion by a cholesterol-independent
      mechanism.

PMID- 8280185
TI  - Medial thinning and atherosclerosis--evidence for involvement of a local
      inflammatory effect.
AB  - Medial attenuation in relation to atherosclerotic plaques is poorly understood.
      We investigated the potential role of a local inflammatory response. Segments of
      carotid artery and descending aorta were studied. The samples were grossly normal
      (n = 10), presented circumscribed atherosclerotic plaques (n = 19) or confluent
      atherosclerotic lesions (n = 8). Tissues were fixed in formalin or snap frozen in
      liquid nitrogen. Sections were stained with conventional staining methods and
      immunohistochemically (smooth muscle cells, macrophages, and T and B
      lymphocytes). Medial thickness was measured with an ocular micrometer;
      inflammatory infiltrates and medial vascularization were assessed
      semiquantitatively. Increasing severity of intimal lesions was accompanied by a
      significant increase in medial inflammation and vascularization and by a
      significant decrease in medial thickness. The inflammatory infiltrates in the
      media consisted of macrophages and T lymphocytes, localized predominantly around
      vasa vasorum. In advanced atherosclerosis they spread more diffusely.
      Inflammatory cells of the intimal atheroma also penetrated the media. At sites of
      inflammation the media contained HLA-DR positive smooth muscle cells with loss of
      collagen. The media in confluent atherosclerosis was almost devoid of smooth
      muscle cells, with loss of collagen and focal fibrosis. We postulate that the
      inflammatory reaction in the media relates to atherosclerosis, has a remodelling
      effect on medial tissues and may cause medial attenuation.

PMID- 8280186
TI  - The immediate effect of streptokinase on serum lipoprotein(a) concentration and
      the effect of myocardial infarction on serum lipoprotein(a), apolipoproteins A1
      and B, lipids and C-reactive protein.
AB  - Lipoprotein(a) (Lp(a)) has close structural homology with plasminogen and, at
      least in vitro, may interfere with fibrinolysis. Any changes in the serum Lp(a)
      concentration during and following myocardial infarction (MI) and whether the
      serum Lp(a) level is affected by streptokinase (SK) are therefore of interest.
      Serum Lp(a) levels immediately before and 3 h after completion of an intravenous
      infusion of SK in 39 patients with acute MI were not significantly different
      (median 31.3 mg/dl before and 35.9 mg/dl after). Furthermore, SK added during the
      serum Lp(a) assay did not affect the result, except at very high concentrations
      of SK (1000 units/ml). Serum Lp(a) and fasting lipids were measured daily for 3
      days following definite MI in 13 patients and then after 14 and 42 days. There
      was no significant change in serum Lp(a) following MI. In marked contrast, C
      reactive protein levels in these patients increased steeply immediately following
      MI. Thus, there was no early 'acute-phase response' in serum Lp(a) levels after
      MI. However, greater variation in its concentration was observed at day 14 than
      at other times. Serum cholesterol, apolipoprotein B and apolipoprotein A1
      concentrations decreased significantly following MI, whereas a significant
      transient increase in serum triglycerides occurred. Forty-two days after MI all
      lipid and lipoprotein values had regained their day 1 levels, except for apo A1,
      which remained depressed.

PMID- 8280187
TI  - Probucol and other antioxidants prevent the inhibition of endothelium-dependent
      relaxation by low density lipoproteins.
AB  - Hypercholesterolaemia and atherosclerosis impair responses to endothelium-derived
      nitric oxide (EDRF) in human and animal coronary arteries, a dysfunction that
      correlates with elevated low density lipoproteins (LDL). Previous studies show
      that native LDL immediately and reversibly inhibit acetylcholine-evoked EDRF
      responses in rabbit aortic ring precontracted with noradrenaline or serotonin
      whereas Cu(2+)-oxidised LDL (oxLDL) inhibit relaxations after 30 min with a
      potency that varies with the donor. We now show that antioxidants, probucol (10
      microM) and ascorbic acid (100 microM) in vitro, prevent the inhibition by native
      LDL, indicating that this effect involves free radicals. As expected, the
      antioxidants had no influence on the inhibition by oxLDL. Superoxide dismutase
      appeared to have no effect on the inhibition by native or oxLDL. The oral
      administration of probucol to selected volunteers also prevented the inhibition
      of relaxation by their native LDL. These preparations showed a diminished
      susceptibility to oxidation and their oxLDL caused a markedly reduced and always
      reversible inhibition of relaxation compared to the potent and sometimes
      irreversible inhibition prior to administration of the drug. We conclude that
      antioxidants such as probucol reduce the formation of free radicals and the
      oxidative modification of LDL that lead to the impairment of EDRF responses and
      may prevent this same dysfunction in hypercholesterolaemia and atherosclerosis.

PMID- 8280188
TI  - Diet and exercise are equally effective in reducing risk for cardiovascular
      disease. Results of a randomized controlled study in men with slightly to
      moderately raised cardiovascular risk factors.
AB  - To study the impact of diet and exercise and the combination thereof on
      cardiovascular risk factors, 157 healthy men aged 35-60 years (mean +/- S.D.;
      46.2 +/- 5.0) with slightly to moderately raised cardiovascular risk factors,
      were randomized to 4 groups, diet (D, n = 40), exercise (E, n = 39), diet plus
      exercise (DE, n = 39), and no active intervention (controls (C, n = 39)), and
      investigated at baseline and after 6 months. BMI was significantly reduced in
      Groups E and DE (mean difference and 95% confidence intervals (CI), -0.3 (-0.5, 
      0.01) and -0.6 (-0.9, -0.3) kg/m2, respectively). Waist circumference was reduced
      in all 3 intervention groups (D, E, and DE), -1.3 (-2.5, -0.1), -2.2 (-3.2, -1.3)
      and -3.0 (-3.9, -2.0) cm, but not in the control group. Blood pressure (BP) was
      reduced in all 3 intervention groups, systolic BP 4-7 mmHg and diastolic BP 2-6
      mmHg. Serum cholesterol was reduced in Group DE, -0.45 (-0.77, -0.13) mmol/l.
      VLDL-cholesterol was reduced in Groups E and DE, -0.14 (-0.26, -0.03) and -0.09 (
      0.18, -0.01) mmol/l, whereas LDL-cholesterol was reduced in Groups D and DE -0.30
      (-0.54, -0.06) and -0.35 (-0.64, -0.05) mmol/l. In contrast, neither HDL
      cholesterol nor serum triglycerides were influenced by the interventions.
      According to the coronary risk profile derived from the Framingham study, all 3
      intervention groups (D, E, and DE) significantly reduced their estimated 10-year
      risk (-13, -12, and -14%, respectively). We conclude that even with rather
      moderate changes in diet and exercise, several important cardiovascular risk
      factors can be affected and that diet and exercise were about equally effective
      in reducing cardiovascular risk.

PMID- 8280189
TI  - Antiatherosclerotic effects of oral cicaprost in experimental
      hypercholesterolemia in rabbits.
AB  - The efficacy of the oral prostacyclin mimetic cicaprost in preventing
      atheromatous plaque formation was studied in an in vivo model of experimental
      hypercholesterolemia. New Zealand white rabbits were fed either standard chow or
      a cholesterol-enriched (1%) diet for 12 weeks. Cicaprost was added to the
      drinking water in a non-hypotensive dose (5 micrograms/kg/day) and withdrawn 3
      days prior to studying platelet, leukocyte and endothelial function. In
      cholesterol-fed rabbits, oral cicaprost reduced the aortic intimal surface
      covered by atheromatous lesions from 84 to 63% (P < 0.05). There was no major
      difference in serum lipid composition between cicaprost- and vehicle-treated
      animals. In hyper-cholesterolemic rabbits there was a significant impairment of
      endothelium-dependent relaxations. Cicaprost treatment considerably improved this
      endothelial function but had no effect in rabbits receiving standard diet. In
      addition, platelet and leukocyte hyperreactivity, as seen in hypercholesterolemic
      rabbits, were largely reduced by cicaprost treatment. These data are the first to
      demonstrate marked antiatherosclerotic effects of long-term oral prostacyclin
      treatment. The mechanism may be related to improved endothelial function and
      subsequent prevention of secondary platelet and neutrophil hyperreactivity.

PMID- 8280190
TI  - Small bowel infarction in association with giant cell arteritis.
AB  - Giant cell arteritis is not uncommonly found in extracranial arteries in
      postmortem studies of patients with temporal arteritis. Presentation with
      vasculitis involving extracranial arteries is, however, unusual. This report
      describes a case of giant cell arteritis presenting with and complicated by
      infarction of the small bowel. Following surgical resection of the infarcted
      segment of bowel and commencement of steroid therapy, the patient is now well and
      free of symptoms. The literature concerning extracranial and in particular small
      bowel giant cell arteritis is reviewed.

PMID- 8280191
TI  - Airbag-associated ocular injury and periorbital fractures.

PMID- 8280192
TI  - Application of an algorithm for staging small-cell lung cancer can save one third
      of the initial evaluation costs.
AB  - OBJECTIVE: Design of a cost-effective algorithm for staging disease in patients
      with small-cell lung cancer. DESIGN: An algorithm was constructed by analyzing
      all permutations of a sequence of procedures required to stage disease in
      patients with small-cell lung cancer. Procedural costs were determined, and the
      model was applied to the small-cell lung cancer patient population treated at the
      National Cancer Institute, Bethesda, Md, from 1973 to 1989. The final algorithm
      was derived from the permutation with the lowest cost per accurately staged
      patient. SETTING: A single government institute, the National Cancer Institute.
      PATIENTS: Four hundred fifty-one patients with previously untreated, consecutive
      histologically documented small-cell lung cancer entered into therapeutic
      protocols at the National Cancer Institute from April 1973 through July 1989.
      Data were obtained from small-cell lung cancer protocol databases and patients'
      medical records. MAIN OUTCOME MEASURE: The cost per patient of each sequence of
      staging procedures when applied to the patient population. RESULTS: The least
      expensive sequence of procedures saved $1418 per patient when compared with
      application of a standard set of staging procedures to all patients. The major
      factor in reducing costs was the concept of stopping the staging procedures after
      a site of distant metastatic disease had been identified. CONCLUSIONS: An
      algorithm consisting of a set of sequential staging procedures can accurately
      stage disease in patients with small-cell lung cancer and save more than one
      third of the costs of an inclusive standard set of staging procedures.

PMID- 8280193
TI  - Mammographic accuracy and patient age: a study of 297 patients undergoing breast
      biopsy.
AB  - This study was undertaken to compare the diagnostic accuracy of mammography in
      patients under 50 years with that of patients over 50, and with further
      subdivisions under 35 and 65 years. A retrospective review of the mammograms of
      297 sequential patients undergoing mammography prior to surgical breast biopsy at
      the Breast Unit, Royal Marsden Hospital, London from 1988-1991 was performed. The
      films were reviewed blind by a single radiologist and correlated with
      histological findings at biopsy. The sensitivity and specificity of mammography
      compared with histology in four age-groups was assessed. There were 144 patients
      in the under-50 age group (< 35 years = 20, 35-49 years = 124), and 153 patients
      aged over 50 (50-64 years = 96, > 65 years = 57). Of all patients with
      histologically malignant biopsies 79% of the under-50s and 76% of the over-50s
      were diagnosed mammographically. Sensitivity of mammography was therefore 3%
      greater in the under-50 age-group (95% confidence interval (CI): +16% to -10%).
      Of patients who had benign biopsies, 76% of the under-50s and 75% of the over-50s
      were correctly diagnosed by mammography. Mammographic specificity was therefore
      1% greater in the over-50 age-group (95% confidence interval: +15% to -14%).
      Accuracy of mammography was also comparable in the four subdivided age-groups.
      The results suggest that in patients requiring breast biopsy, contemporary
      mammography is similar in accuracy in the younger patient when compared to the
      older post-menopausal patient.

PMID- 8280194
TI  - Hierarchical gene diversity and genetic structure of tribal populations of Andhra
      Pradesh, India.
AB  - Gene diversity and genetic structure of tribal populations of Andhra Pradesh,
      India, have been analyzed under a hierarchical model consisting of five regions
      of the state, tribes within the regions, and local subpopulations within the
      tribes. Average gene diversity has been estimated from gene frequency data for 15
      polymorphic loci by using nested gene diversity analysis of GST. The
      intralocation coefficient of gene diversity was estimated at 96% of the total,
      whereas the intertribal, within--and between--regional gene diversities were
      found to be only 1.90, 0.95, and 1.43%, respectively. The estimate of gene
      diversity was higher for loci with higher degrees of polymorphism such as ABO,
      MN, ESD, and PTC and lower for loci with low-level polymorphism and extreme gene
      frequencies such as Hb, Tf, PHI, 6PGD, and Hp. The nature of selective preference
      or neutrality at the loci seems to be important in this respect. Tribes of the
      plains exhibit the least gene diversity, apparently because of higher gene flow
      among them. The contribution of loci with intermediate gene frequencies in
      intertribal and regional gene diversity was found to be higher than for loci with
      extreme allelic frequencies. These results suggest that the most significant
      component of variation is between individuals within locations and that variation
      between local subpopulations is negligible in the genetic structure of a
      population. Forces like selection, gene flow and drift also influence the
      diversity depending upon the nature of the locus.

PMID- 8280195
TI  - Corticosteroid therapy does not prevent nephritis in Henoch-Schonlein purpura.
AB  - Nephritis occurs in 20%-50% of children with Henoch-Schonlein purpura (HSP), and
      the onset of renal involvement may be delayed for weeks or months in a
      substantial proportion of patients. The present study was performed to determine
      whether corticosteroid therapy was effective in preventing delayed nephritis in
      children with HSP. The medical records of 69 children with HSP were reviewed.
      Nineteen patients had acute nephritis occurring from 1-12 days after the onset of
      other signs and symptoms. The remaining 50 patients had no evidence of acute
      renal involvement. Of these 50 patients, 20 were treated during the acute phase
      of the illness with corticosteroids, while 30 never received corticosteroid
      therapy. Delayed nephritis (> 3 weeks following an initial normal urinalysis)
      occurred in 4 of 20 (20%) patients who received prior corticosteroid treatment,
      and in 6 of 30 (20%) patients who were not treated. These results indicate that
      early corticosteroid therapy does not prevent delayed nephritis in children with
      HSP.

PMID- 8280196
TI  - Orthodontic practice in The Netherlands.
AB  - Free movement of dental practitioners between the United Kingdom and The
      Netherlands presents no registration problems. Difficulties still exist for the
      registration of orthodontic specialists, but these should be solved with the
      introduction of the specialist register in Britain. Information is presented here
      which describes the mechanism for registration.

PMID- 8280197
TI  - A simplified method for quantification of myocardial blood flow using nitrogen-13
      ammonia and dynamic PET.
AB  - The utility of Patlak graphical analysis was investigated for quantification of
      regional myocardial blood flow (MBF) and for generating parametric images of MBF
      with 13N-ammonia and dynamic PET imaging in dogs and humans. MBF was estimated by
      a two-compartment model fit of the initial 2 min of the kinetic data and by
      Patlak graphical analysis of the initial 2, 3, or 4 min of data. In 11 dog
      studies, MBF by compartmental model fitting linearly correlated with MBF by
      microspheres (correlation coefficient (r) = 0.99, slope = 0.92) and by Patlak
      graphical analysis (r = 0.99, slope = 0.90). In 10 normal human studies, MBF
      obtained by the Patlak graphical analysis agreed well with MBF obtained by the
      compartmental model fitting (r = 0.96, slope = 1.04). Good agreement of the MBF
      estimates was also observed in 10 coronary artery disease patient studies (r =
      0.96). Patlak graphical analysis permitted generation of parametric images of
      MBF. The parametric images of MBF, in units of ml/min/g, are of good image
      quality and have relatively low noise levels. We conclude that regional MBF can
      be noninvasively and conveniently measured with dynamic 13N-ammonia PET using
      either a two-compartment model or Patlak graphical analysis. MBF parametric
      images generated with the Patlak graphical analysis both map the distribution and
      quantitate the magnitude of myocardial perfusion abnormalities.

PMID- 8280198
TI  - Risk factors for complications of chronic anticoagulation. A multicenter study.
      Warfarin Optimized Outpatient Follow-up Study Group.
AB  - OBJECTIVE: To define risk factors for complications that occur during warfarin
      therapy. DESIGN: Retrospective cohort study. SETTING: Five anticoagulation
      clinics. PATIENTS: Nine hundred twenty-eight consecutive patients receiving 1103
      courses of warfarin. MAIN OUTCOME MEASURES: Hemorrhagic and thromboembolic
      complications. RESULTS: In 1950 patient-years of follow-up, there were 1332
      bleeding events (4 were classified as fatal, 31 as life-threatening, 226 as
      serious, and 1071 as minor). The cumulative incidence of fatal bleeding was 1% at
      1 year and 2% at 3 years. The cumulative incidences of first episodes of life
      threatening and serious bleeding at 1, 2, 4, and 8 years were 1%, 2%, 5%, and 9%
      and 12%, 20%, 28%, and 40%, respectively. Of 156 patients who had a serious or
      life-threatening hemorrhage, 32% suffered a recurrence, typically within 1 year.
      Independent predictors of a first episode of serious bleeding included a mean
      prothrombin time ratio (PTR) of 2.0 or more during the course of treatment
      (relative risk, 3.0; 95% CI, 1.9 to 4.7); recent initiation of warfarin therapy
      (relative risk during the first 3 months compared with the rest of the first
      year, the second year, and anytime thereafter, 1.9 [CI, 1.3 to 3.0], 3.0 [CI, 1.8
      to 4.8], and 5.9 [CI, 3.8 to 9.3], respectively); variability of the PTR over
      time (relative risk for the highest compared with the lowest tertile, 1.6 [CI,
      1.2 to 2.7]); and the presence of 3 or more comorbid conditions (RR, 1.4 [CI, 1.1
      to 2.5]). Age, reason for anticoagulation, use of interfering drugs, and
      hypertension were not associated with risk for bleeding. The risk for a
      thromboembolic complication at a PTR of less than 1.3 was 3.6 (CI, 2.1 to 6.4)
      times higher than at a PTR of 1.3 to 1.5. CONCLUSIONS: The incidence of warfarin
      associated bleeding may be reduced by attending to modifiable risk factors (that
      is, highly variable PTRs and values greater than 2.0), frequent monitoring early
      in treatment, and careful patient selection. Older age, in and of itself, is not
      a risk factor.

PMID- 8280199
TI  - Achromobacter xylosoxidans osteomyelitis.

PMID- 8280200
TI  - Spontaneous recurrence of acute epidural hematoma: a case report.
AB  - A mildly symptomatic epidural hematoma, imaged by computed tomography (CT),
      appeared to resolve within 24 hours but then recurred 4 days later. The recurrent
      hematoma gradually resolved spontaneously and the patient became asymptomatic.

PMID- 8280201
TI  - Snoring, sleep disturbance, and behaviour in 4-5 year olds.
AB  - Parents of 996 children aged 4-5 years identified consecutively from the Oxford
      health visitor register were asked to complete a questionnaire about breathing
      disorders during sleep. A total of 782 (78.5%) was returned. Ninety five (12.1%)
      children were reported to snore on most nights. Habitual snoring was
      significantly associated with daytime sleepiness, restless sleep, and
      hyperactivity. The questionnaire responses were used to select two subgroups, one
      at high risk of a sleep and breathing disorder and a control group. These
      children (132 in total) were monitored at home with overnight video recording and
      oximetry, and had formal behavioural assessment using the Conners scale. Seven
      (7/66) children from the high risk group and none from the control group had
      obvious sleep disturbance consequent on snoring and upper airway obstruction.
      Thus our estimate of the prevalence of sleep and breathing disorders in this age
      group is 7/996 or 0.7%. The high risk group had significantly higher nocturnal
      movement, oxygen saturation dip rates, and overnight pulse rates than the
      controls. Maternal but not paternal smoking was associated with the high risk
      group. Parents and teachers thought those in the high risk group were more
      hyperactive and inattentive than the controls, but only their parents thought
      them more aggressive. Significant sleep and breathing disorders occur in about
      0.7% of 4-5 year olds. Children whose parents report snoring and sleep
      disturbance have objective evidence of sleep disruption and show more behaviour
      problems than controls.

PMID- 8280202
TI  - Alpha 4 beta 1 recognition of the Hep II domain of fibronectin is constitutive on
      some hemopoietic cells but requires activation on others [corrected].
AB  - Leukocyte adhesion to the carboxyl-terminal region of fibronectin, a major
      component of extracellular matrices, involves recognition of the CS-1 site and
      the Hep II domain. We have previously shown that cultured T and B lymphoid cells
      constitutively attach via the alpha 4 beta 1 integrin to a 38-kDa fibronectin
      fragment that contains CS-1 and Hep II, and to a 58-kDa fragment that contains
      Hep II only. In this report we have studied the adhesion of other hemopoietic
      cells to the CS-1 and Hep II regions of fibronectin. Cultured monocytic cells and
      peripheral blood T lymphocytes constitutively bound to the 38-kDa fragment
      indicating that alpha 4 beta 1 was functional. These cells, however, were unable
      to bind to the 58-kDa fragment. On lymphoid cells both fragments were shown to
      bind to very close regions of alpha 4 beta 1 as indicated by the inhibition
      pattern of mAb to various alpha 4 epitopes, and by the good inhibitory capacity
      of soluble 38-kDa fragment on cell adhesion to 58-kDa fragment. These results
      suggested that alpha 4 beta 1 is present on certain cell populations as a
      partially active form able to recognize the "high affinity" ligand CS-1 but not
      the "low affinity" ligand Hep II. Binding of monocytic cells and peripheral blood
      T lymphocytes to the Hep II domain could be induced by several agents: first,
      long (48-h) and short (20-min) treatment with phorbol esters; second, cell
      incubation with the divalent cation Mn2+; third, and most effective, cell
      incubation with the mAb TS2/16, which is directed to the beta 1 integrin subunit.
      Binding to the 58-kDa fragment in all three cases was completely inhibited by mAb
      anti-alpha 4, thus confirming the involvement of alpha 4 beta 1 in the
      recognition of the Hep II domain. No major changes on alpha 4 beta 1 surface
      expression were observed after these treatments as determined by
      immunofluorescence analyses. Our results indicate that hemopoietic cells may
      differentially bind the CS-1 and Hep II ligands in fibronectin depending on the
      activation state of alpha 4 beta 1, a fact that may be relevant for the migration
      and function of leukocytes.

PMID- 8280203
TI  - Correcting generalized gingival recession.
AB  - Recession associated with the maxillary anterior gingiva can be particularly
      displeasing to the patient with a high smile line. The coronally positioned flap
      technique was used in this case to create a more esthetic appearance.

PMID- 8280204
TI  - Radiologic recommendations in cases of gastric ulcer.

PMID- 8280205
TI  - Codependency: a feminist perspective.
AB  - 1. Our understanding of psychological life has been underdeveloped and distorted
      because explanations have been created by only one half of the human species. The
      current broad and encompassing disease definition of codependency may devalue
      some of women's greatest strengths. 2. The disease model of codependency, it may
      be argued, is rooted in extant, reductionist models that suggest a developmental
      pathway of separation and individuation leading to an autonomous and independent
      maturity. 3. The feminist model of Growth in Connection proposes that the
      flowering of the self occurs within the development and maintenance of
      relationships in which accurate and mutual empathy is both the goal and the
      motivation toward growth.

PMID- 8280206
TI  - The plagues of Egypt: what killed the animals and the firstborn?
AB  - The Book of Exodus, various translations, chapters 7 to 12--The plagues: 1. The
      river Nile turned the colour of blood, the water stank and the fish died 2.
      Hordes of frogs left the river, then they died and their bodies stank 3. Swarms
      of gnats attacked the people and their animals 4. Swarms of flies then did the
      same 5. An epidemic disease killed many farm animals 6. Boils and skin sores
      broke out on the people and their animals 7. A violent hail storm ruined the
      crops 8. A swarm of locusts ate what was left of them 9. Darkness blanketed the
      country for three days 10. The eldest child in each family died suddenly, and so
      did the first born animals. THE PERIOD: Uncertain, but deduced to be about 1470
      BC. THE PEOPLE: The Egyptians, a population of about 2.5 million, about one
      million living in the Nile delta at an average density of about 90 people per km2
      of cultivated land, and the Israelites, working as slave-labourers and quartered
      in the land of Goshen, a relatively small area probably near the margin of the
      north-east part of the Nile delta. THE PROTAGONISTS: Thutmosis III, Pharoah of
      Egypt, and Moses, leader of the Israelites. THE PLACE: The encounters between
      Thutmosis and Moses occurred just before each of the plagues, in or close to the
      Pharoah's palace. Given Moses' location, this must have been the palace at
      Memphis, the old capital, near the southern apex or beginning of the delta, not
      the one at Thebes, 600 km further to the south along the river. The Israelites'
      perception of the geographical extent of the plagues was therefore limited to
      what happened in the delta. The statements that plagues 1, 2, 3 and 8 affected
      "all the land of Egypt" should be interpreted as: all of the Nile delta including
      the land of Goshen. The other plagues affected parts neighbouring on, but not
      including, the land of Goshen.

PMID- 8280207
TI  - Is fetal medicine a reality?

PMID- 8280209
TI  - The growth of South African rural black children.
AB  - The growth status of two samples of South African rural black children, from
      Ubombo, KwaZulu, and Vaalwater, northern Transvaal, was compared with that of
      samples of American black children and three other rural sub-Saharan groups. All
      the sub-Saharan black children were shorter, lighter and had less subcutaneous
      fat than the American children. Their growth curves demonstrated the well
      recognised pattern of deviation from American means before adolescence so that,
      by the start of adolescence, approximately 50% of the children were below the
      10th centile of American norms. Adolescence in all groups is delayed and the
      magnitude of peak velocity reduced. The adolescent growth spurt appears, however,
      to be extended along the time base so that pre- and post-peak velocities are
      raised; this leads to apparent catch-up growth in the late teenage years. While
      the Vaalwater sample demonstrated growth patterns very similar to those of other
      rural sub-Saharan black groups, the Ubombo children were consistently taller and
      heavier than all the others. These data are discussed in relation to the need for
      national norms that reflect the growth status of black South African children.

PMID- 8280208
TI  - Mercury released from dental "silver" fillings provokes an increase in mercury-
      and antibiotic-resistant bacteria in oral and intestinal floras of primates.
AB  - In a survey of 640 human subjects, a subgroup of 356 persons without recent
      exposure to antibiotics demonstrated that those with a high prevalence of Hg
      resistance in their intestinal floras were significantly more likely to also have
      resistance to two or more antibiotics. This observation led us to consider the
      possibility that mercury released from amalgam ("silver") dental restorations
      might be a selective agent for both mercury- and antibiotic-resistant bacteria in
      the oral and intestinal floras of primates. Resistances to mercury and to several
      antibiotics were examined in the oral and intestinal floras of six adult monkeys
      prior to the installation of amalgam fillings, during the time they were in
      place, and after replacement of the amalgam fillings with glass ionomer fillings
      (in four of the monkeys). The monkeys were fed an antibiotic-free diet, and fecal
      mercury concentrations were monitored. There was a statistically significant
      increase in the incidence of mercury-resistant bacteria during the 5 weeks
      following installation of the amalgam fillings and during the 5 weeks immediately
      following their replacement with glass ionomer fillings. These peaks in incidence
      of mercury-resistant bacteria correlated with peaks of Hg elimination (as high as
      1 mM in the feces) immediately following amalgam placement and immediately after
      replacement of the amalgam fillings. Representative mercury-resistant isolates of
      three selected bacterial families (oral streptococci, members of the family
      Enterobacteriaceae, and enterococci) were also resistant to one or more
      antibiotics, including ampicillin, tetracycline, streptomycin, kanamycin, and
      chloramphenicol. While such mercury- and antibiotic-resistant isolates among the
      staphylococci, the enterococci, and members of the family Enterobacteriaceae have
      been described, this is the first report of mercury resistance in the oral
      streptococci. Many of the enterobacterial strains were able to transfer mercury
      and antibiotic resistances together to laboratory bacterial recipients,
      suggesting that the loci for these resistances are genetically linked. Our
      findings indicate that mercury released from amalgam fillings can cause an
      enrichment of mercury resistance plasmids in the normal bacterial floras of
      primates. Many of these plasmids also carry antibiotic resistance, implicating
      the exposure to mercury from dental amalgams in an increased incidence of
      multiple antibiotic resistance plasmids in the normal floras of nonmedicated
      subjects.

PMID- 8280210
TI  - Liver cirrhosis in cystic fibrosis--therapeutic implications and long term follow
      up.
AB  - Experience gained from liver studies in 450 patients with cystic fibrosis, seen
      in a 38 year period from 1964 to 1992, is surveyed. Of these, 31 (7%) showed
      findings that indicated multilobular cirrhosis. There was a slight but not
      significant male predominance: 19 males against 12 females. Liver disease had its
      onset during childhood in most cases. The natural course of liver disease and of
      cirrhosis is protracted. All patients were routinely evaluated by way of: (i)
      clinical examination, (ii) biochemical studies and specifically estimation of
      transaminases and gamma glutamyltransferase, and (iii) liver imaging,
      ultrasonography, and computed tomography. The study aimed to detect early liver
      disease, that is multilobular cirrhosis and its complications, with a view to
      optimal introduction of treatment with ursodeoxycholic acid as this drug shows
      promise for preventing or stabilising the cirrhotic process. Effects of surgical
      treatment on portal hypertension are surveyed. These include portacaval shunting,
      partial splenectomy (considered the procedure of choice), liver transplant in the
      event of liver failure, or a triple transplant (liver, lungs, and heart) if
      necessary. One triple transplant was successfully performed in a boy of 10 years
      with a 2 year follow up.

PMID- 8280211
TI  - Dental education and board examinations in the U.S.

PMID- 8280212
TI  - Mohs surgery explained.

PMID- 8280213
TI  - Do clinical guidelines improve general practice management and referral of
      infertile couples?
AB  - OBJECTIVE: To evaluate guidelines for general practice management and referral of
      infertile couples. Guidelines were implemented with a disease specific reminder
      at the time of consultation (the guidelines were embedded within a structured
      infertility management sheet for each couple). DESIGN: Pragmatic randomised
      controlled trial. Participating practices were randomised to a group that
      received the guidelines and a control group. SETTING: 82 general practices in
      Grampian region. SUBJECTS: 100 couples referred by general practitioners
      receiving the guideline and 100 couples referred by control general
      practitioners. MAIN OUTCOME MEASURES: Whether the general practitioner had taken
      a full sexual history and examined and investigated both partners appropriately.
      RESULTS: Characteristics of patients referred by study and control general
      practitioners did not differ significantly at baseline. Compliance with the
      guidelines increased for all targeted activities. General practitioners in the
      study group were more likely to take a sexual history (for example, couples' use
      of fertile period, 85% v 69%, p < 0.01); examine both partners (female partner,
      68% v 52%, p < 0.05; male partner 39% v 13%, p < 0.01); and investigate both
      partners (day 21 progesterone, 72% v 41%, p < 0.001; semen analysis, 51% v 41%, p
      > 0.05). Improvements were greater when general practitioners used the disease
      specific reminder. CONCLUSION: Receiving guidelines led to improvements in the
      process of care of infertile couples within general practice. This effect was
      enhanced when the guidelines were embedded in a structured infertility management
      sheet for each couple.

PMID- 8280214
TI  - Heparin induced thrombosis: an important complication of heparin prophylaxis for
      thromboembolic disease in surgery.
AB  - Heparin induced thrombocytopenia with thrombosis, or the "white clot syndrome,"
      is a rare but recognised complication of heparin therapy. The syndrome is
      idiosyncratic, immune mediated, and not dose dependent and therefore is equally
      likely to occur with prophylactic and therapeutic heparin dosage regimens.
      Despite published reports on the subject we were alarmed that many surgeons who
      regularly use heparin to prevent or treat thrombosis were unaware that heparin
      can induce thrombotic complications in susceptible patients. We present three
      typical case histories, a brief discussion of the condition, and some guidelines
      on its prevention and treatment.

PMID- 8280215
TI  - Assessment of thyroid status in elderly people.

PMID- 8280216
TI  - Confidentiality for doctors with AIDS.

PMID- 8280217
TI  - The nursing way of death.

PMID- 8280218
TI  - Corticosteroid therapy in Henoch-Schonlein purpura.

PMID- 8280219
TI  - Need the free radical theory of aging be linked to the metabolic rate theory?

PMID- 8280220
TI  - A time for listening.

PMID- 8280221
TI  - Routine ultrasound scanning in pregnancy. The benefits are clinical ... and
      psychological.

PMID- 8280222
TI  - The Hawksley random zero sphygmomanometer. No harm done.

PMID- 8280223
TI  - Searching MEDLINE for randomised trials.

PMID- 8280224
TI  - Confidentiality for doctors with AIDS. Conflict between patient's and doctors'
      rights.

PMID- 8280225
TI  - Reference management software. Confusion in the appendices.

PMID- 8280226
TI  - Fetal blood sampling in retreat.

PMID- 8280227
TI  - The Calman report. Service implications uncertain.

PMID- 8280228
TI  - Functional hypoglycaemia postulated as cause of chronic fatigue syndrome.

PMID- 8280229
TI  - Spinal cord stimulation or ischaemic preconditioning?

PMID- 8280230
TI  - Medical treatment at the Glastonbury Festival. Costs are predictable.

PMID- 8280231
TI  - Primary care and public health. Have a lot in common.

PMID- 8280232
TI  - Epidemiology of vascular dementia.

PMID- 8280233
TI  - Tobacco company advertising.

PMID- 8280234
TI  - Familial cystic nephroma and pleuropulmonary blastoma.

PMID- 8280235
TI  - Digoxin immunoassay and Chinese medicine.

PMID- 8280236
TI  - Testicular microlithiasis and seminoma.

PMID- 8280237
TI  - Pneumocystis carinii pneumonia and methotrexate therapy.

PMID- 8280238
TI  - Mechanisms of fluid secretion induced by cAMP and related agents in gallbladder.

PMID- 8280239
TI  - Open access gastroscopy.

PMID- 8280240
TI  - Barrett's oesophagus and development of dysplasia and adenocarcinoma.

PMID- 8280241
TI  - Isolated sternal fracture: a benign injury?

PMID- 8280242
TI  - Cardiopulmonary exercise testing after balloon mitral valvuloplasty (PBMV)

PMID- 8280243
TI  - Postvaccination sarcomas in cats.

PMID- 8280244
TI  - Myths or truths of adolescence?

PMID- 8280245
TI  - Burn units in Great Britain and the National Health Service.

PMID- 8280246
TI  - Laboratory dogs.

PMID- 8280247
TI  - Tissue artefacts caused by sponges.

PMID- 8280248
TI  - Coalition for oral health.

PMID- 8280249
TI  - Carbohydrate counting alternative in glucose control.

PMID- 8280250
TI  - Footwear and balance in older men.

PMID- 8280251
TI  - Neurobiology of chronic peptic ulcer disease.

PMID- 8280252
TI  - "Back mouse".

PMID- 8280253
TI  - In an era of tough choices, what is your comfort level?

PMID- 8280254
TI  - Voluntary organ donation: autonomy ... tragedy.

PMID- 8280255
TI  - Pulmonary artery catheterization: developing guidelines.

PMID- 8280256
TI  - The computerized medical record is not the patient analog. A four partners
      scenario in clinical encounters.

PMID- 8280258
TI  - Mohs surgery explained.

PMID- 8280257
TI  - Compression bandaging for snake bite.

PMID- 8280259
TI  - Polyneuropathy associated with IgA monoclonal gammopathy of undetermined
      significance.

PMID- 8280260
TI  - Abdominal aortic aneurysm.

PMID- 8280261
TI  - Recent advances in pulmonary medicine.

PMID- 8280262
TI  - Sexual orientation.

PMID- 8280263
TI  - Cerebellar cognition.

PMID- 8280264
TI  - PET, MRI, and epilepsy.

PMID- 8280265
TI  - Statistical aspects of survival.

PMID- 8280266
TI  - Acuity through discolored lenses.

PMID- 8280267
TI  - Dr. Cook and his claims.

PMID- 8280268
TI  - Atrial systolic failure in cardiac amyloidosis.

PMID- 8280269
TI  - The NIH Intramural Program.

PMID- 8280270
TI  - Suction v. conventional curettage in incomplete abortion.

PMID- 8280271
TI  - Reversal of acute resistant asthma by beclomethasone.

PMID- 8280272
TI  - Spontaneous recurrence of acute epidural haematoma: a case report.

PMID- 8280273
TI  - Five Ps can be misleading.

PMID- 8280274
TI  - Don't forget the lancet.

PMID- 8280275
TI  - Response to somatic treatment and placebo in patients with melancholia/endogenous
      depression.

PMID- 8280276
TI  - Use of the laryngeal mask airway in resuscitation.

PMID- 8280277
TI  - Patient-controlled epidural analgesia following post-traumatic pelvic
      construction.

PMID- 8280278
TI  - Cost of anaesthesia for minor surgery.

PMID- 8280279
TI  - Subarachnoid block as an adjunct to extradural anaesthesia.

PMID- 8280280
TI  - Epidural anesthesia and peroneal nerve injury.

PMID- 8280281
TI  - Sleep apnea and the risk for perioperative myocardial infarction.

PMID- 8280282
TI  - Managing anticoagulation safely.

PMID- 8280283
TI  - The use of Coca-Cola in the management of bolus obstruction in benign oesophageal
      stricture.

PMID- 8280284
TI  - Clarification about artificial urinary sphincters.

PMID- 8280285
TI  - Congenital aortic stenosis and patent ductus arteriosus in the adult.

PMID- 8280286
TI  - Fatal deterioration of Wilson's disease after institution of oral zinc therapy.

PMID- 8280287
TI  - Patient selection in the Timpilo Study.

PMID- 8280288
TI  - Effect of varying proportions of evening primrose oil and fish oil on cats with
      crusting dermatosis ('miliary dermatitis')
AB  - Fourteen cats with crusting dermatoses ('miliary dermatitis') were supplemented
      with various combinations of evening primrose oil and fish oil. The cutaneous
      signs improved when the cats were supplemented with either evening primrose oil
      alone or with a combination of evening primrose oil and fish oil. Fish oil alone
      was unable to maintain the remission and the cutaneous signs deteriorated. The
      subsequent administration of a combination of the two oils resulted in a
      resolution of the dermatosis.

PMID- 8280289
TI  - Comparative molecular field analysis of in vitro growth inhibition of L1210 and
      HCT-8 cells by some pyrazoloacridines.
AB  - In vitro screening of a number of 2-(aminoalkyl)-5-nitropyrazolo[3,4,5-
      kl]acridines has previously indicated (Sebolt, J.S.; et al. Cancer Res. 1987, 47,
      4299-4304) that these compounds, in general, exhibit selective cytotoxicity
      against the human colon adenocarcinoma, HCT-8, cell line, relative to mouse
      leukemia L1210 cells. Comparative molecular field analysis (CoMFA) was applied to
      HCT-8 and L1210 growth inhibition assays (IC50s) of a series (44) of the
      pyrazoloacridine derivatives with the objective of predicting improved solid
      tumor selectivity. In the absence of crystallographic data, the 9-methoxy
      derivative (15), which is currently in clinical study, was selected as the
      template molecular model. Two different structural alignments were tested: an
      alignment of structures based on root mean square (RMS)-fitting of each structure
      to 15 was compared with an alternative strategy, steric and electrostatic
      alignment (SEAL). Somewhat better predictive cross-validation correlations (r2)
      were obtained with models based on RMS vis-a-vis SEAL alignment for both sets of
      assays. A large change in lattice spacing, e.g., 2 to 1 A, causes significant
      variations in the CoMFA results. A shift in the lattice of half of its spacing
      had a much smaller effect on the CoMFA data for a lattice of 1 A than one of 2 A.
      The relative contribution of steric and electrostatic fields to both models were
      about equal, underscoring the importance of both terms. Neither calculated log P
      nor HOMO and/or LUMO energies contribute to the model. Steric and electrostatic
      fields of the pyrazoloacridines are the sole relevant descriptors to the
      structure-activity (cross-validated and conventional) correlations obtained with
      the cytotoxic data for both the L1210 and HCT-8 cell lines. The cross-validated
      r2, derived from partial least-squares calculations, indicated considerable
      predictive capacity for growth inhibition of both the leukemia and solid-tumor
      data. Evidence for the predictive performance of the CoMFA-derived models is
      provided in the form of plots of actual vs predicted growth inhibition of L1210
      and HCT-8 cells, respectively, by the pyrazoloacridines. The steric and
      electrostatic features of the QSAR are presented in the form of standard
      deviation coefficient contour maps of steric and electrostatic fields. The maps
      indicate that increases or decreases in steric bulk that would enhance growth
      inhibition of HCT-8 cells would likewise promote growth inhibition of L1210
      cells. Contour maps generated to analyze the electrostatic field contributions of
      the pyrazoloacridines to growth inhibition provide an essentially similar set of
      results.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8280290
TI  - Molecular mechanism of cell death induced dNTP pool imbalance.
AB  - We have previously reported that treatment of the FM3A cells with 5
      fluorodeoxyuridine (FdUrd) induced DNA double strand breaks and cell death. We
      proposed the hypothesis of dNTP pool imbalance death in order to understand these
      phenomena: intracellular dNTP pool imbalance induced by FdUrd would be a trigger
      for activation or induction of endonuclease which would attack DNA to cause
      double strand breaks and subsequent cell death. To observe the mechanism of dNTP
      imbalance death we have purified and characterized the endonuclease that was
      detected in FdUrd treated FM3A cells but not untreated cells. As the result, we
      suggested that purified enzyme is a new endonuclease and responsible for DNA
      degradation component of the apoptotic process. Furthermore, we study that mRNA
      levels of nuclear protooncogenes, c-fos, c-jun and c-myc, in FdUrd-treated cells.
      These results suggested that the endonuclease might be induced by the
      protooncogene related pathway and generates DNA fragments accompanied by cell
      death.

PMID- 8280291
TI  - An aeronautic suicide attempt (2). The psychiatrist's comments.
AB  - A man without previous flying experience stole an aircraft and took off in order
      to commit suicide. An air traffic controller managed to convince him to land the
      plane. This article reports the psychiatrist's investigation into the case.

PMID- 8280292
TI  - [A case of an elderly SLE patient associated with acute renal failure].
AB  - It has been described that a rapid worsening in renal function is uncommon in the
      elderly patient with lupus nephritis. We report a case of a 76-year-old man with
      rapidly progressive lupus nephritis. On admission, laboratory studies revealed
      massive proteinuria, telescoped urine, thrombocytopenia and azotemia.
      Hypocomplementemia and the positive presence of anti-DNA antibody and lupus
      anticoagulant were also noted. Because of a rapid deterioration of renal
      function, he was started on a regimen of steroid pulse therapy and
      plasmapheresis. Serum levels of complements gradually increased after initiation
      of these treatments, and three weeks later, improvements of renal function and
      nephrotic syndrome were obtained. A renal biopsy specimen taken five months after
      admission showed diffuse membranous glomerulonephritis. In addition, we examined
      renal arterial blood flow with Doppler ultrasound, and significant improvements
      of the velocity and pulsatility were observed during recovery of the renal
      function.

PMID- 8280293
TI  - Cooperative social coordination and aggression: II. Effects of sex and housing
      among three strains of intact laboratory rats differing in aggressiveness.
AB  - Pairs of laboratory rats were rewarded with sugar solution for cooperating by
      means of synchronized shuttling in a rectangular chamber. Learning and
      performance were compared in males and females of three strains--S3, Charles
      River, and Wistar--ordered in terms of decreasing levels of aggressiveness. In
      addition, same-sex pairs of each strain were housed either together or
      individually. When housed together, males and females of all strains eventually
      cooperated at comparable levels, with rates of acquisition across strains
      inversely related to their aggressiveness. Individual housing, in contrast, was
      associated with severe deficits in males of the S3 and CR strains linked to
      violent fighting and prolonged freezing by animals who had previously been
      defeated. All other individually housed groups, including males of the Wistar
      strain and females of all strains, were able to cooperate, including S3 females
      whose violent fighting was not associated with immobility by defeated animals. In
      general, the majority of groups were able to cooperate despite differences in
      aggressiveness associated with sex, strain, and housing. Possible processes in
      this accommodation are discussed.

PMID- 8280294
TI  - [The pathologist and chronic viral hepatitis C in 1993].

PMID- 8280295
TI  - [Chronic hepatitis of viral origin].

PMID- 8280296
TI  - [Toxoplasmosis in AIDS patients. Pathoclinical study of 78 cases].
AB  - We report 78 cases of toxoplasmosis diagnosed between 1987 and 1992, from an
      autopsy study of 205 patients infected by the human immunodeficiency virus (HIV).
      Of the 78 patients 22 were females (28%) and 56 males (72%). Risk factors were as
      follows: intravenous drug addiction (44 cases, 56%), homosexuality or bisexuality
      (18 cases; 36%) and multiple blood transfusions (6 cases). Cerebral toxoplasmosis
      (CT) was diagnosed in 73 cases (93%) and was characterized by abscesses (59
      cases), diffuse encephalitic lesions (8 cases), isolated cysts without
      inflammation (3 cases) and hemispheric involvement with ventricular hemorrhage (3
      cases). Cerebral involvement were isolated (55/78 cases; 70%) or associated with
      multi-visceral diffusion (18/78 cases; 23%). Isolated extracerebral localization
      was observed in 5 cases. The most frequent extracerebral sites were: cardiac (21
      cases), pulmonary (14 cases) and pancreatic (7 cases). Immunohistochemical study
      with anti Toxoplasma gondii antibodies allowed to a diagnosis of extracerebral
      localization in 8 cases. Ultrastructural features of Toxoplasma gondii were
      studied on post mortem myocardial samples (2 cases) open lung biopsy (1 case) and
      bladder biopsy specimen (1 case). Antemortem diagnosis of cerebral toxoplasmosis
      was performed on CT-scan in 59/73 (80%). Antemortem diagnosis of extracerebral
      toxoplasmosis was performed or suspected in 8/23 cases (34%): by isolation of
      trophozoites in bronchoalveolar lavage (2 cases), on an open lung biopsy (1 case)
      and on a bladder biopsy specimen (1 case), and by clinical and echocardiographic
      data (4 cases). Anti-toxoplasmic serology allowed to the diagnosis of
      toxoplasmosis in 12/78 cases (15%) by showing high levels of IgG in the
      serum.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280297
TI  - [Olfactory esthesioneuroma (esthesioneuroblastoma). A pathologic study of 7
      cases].
AB  - With an histological, immunohistochemical study of 7 cases of olfactory
      esthesioneuromas (4 of them had an ultrastructural study), our purpose was to
      revise the problem of the too often ambiguous terminology and of the different
      histological lower classes classifications of these tumors. Our own results and
      the literature demonstrate that they are polymorphic. In standard histology, they
      are often right diagnosed but an immunohistochemical study can be useful and an
      ultrastructural study absolutely necessary for a reliable diagnosis. For an
      easier nomenclature, we advise to use only one terminology for these tumors =
      olfactory esthesioneuroma. But, because of their important polymorphism, we keep
      to an histological lower classes classification according to their degree of
      differentiation in light microscopy: well differentiated tumors (old
      esthesioneuroepitheliomas), moderately differentiated tumors (old
      esthesioneurocytomas), poorly differentiated tumors (old esthesioneuroblastomas
      and so on described as neuro-endocrine carcinomas by Silva and al).

PMID- 8280298
TI  - [Parathyroid cyst of the anterior mediastinum].
AB  - A mediastinal cyst measuring 6 cm was removed by manubriotomy in a 66-year-old
      woman. This patient had no clinical or biological evidence of
      hyperparathyroidism. The cyst was close to the thymus and compressed the
      innominate venous trunk. It contained a clear fluid. Normal parathyroid tissue
      was present in the capsular wall that was fibrous and partially calcified. This
      cysts are rare and their mediastinal localization is exceptional.

PMID- 8280300
TI  - [Malignant hemangioendothelioma of the thyroid. Pathologic study of a case].
AB  - The authors report a case of malignant tumor of the thyroid in a 79 years old
      woman with a long standing goiter for 20 years but who did not live in endemic
      mountainous goiter area. The right lobe of the thyroid was surgically removed in
      February 1992 because increasing in size. Pathologic diagnosis was non malignant
      cystic lesion. Two months later, a recurrence with dyspnea urged a tracheostomy.
      The patient died 9 days later because of intra bronchial and pleura hemorrhage.
      The morphological and immuno-histochemical investigations showed angiosarcomatous
      features and positive reactivity with Factor VIII and UEA 1 markers in the tumour
      and pulmonary metastases. The diagnosis of Malignant hemangio-endothelioma was
      concluded.

PMID- 8280299
TI  - [Digestive system metastases from breast cancer. Report of two cases].
AB  - We have reviewed two unusual cases of gastrointestinal metastases from a primary
      breast carcinoma. The first case was an unexpected microscopic discovery of
      metastases in an inguinal hernia sac, eleven years after the patient had surgery
      for breast carcinoma. The second case was a rectal localization from a unknown
      breast carcinoma. The incidence of gastrointestinal metastasis from breast
      carcinoma is underestimated because they have a long latency and screening is
      difficult. Histologically they are predominantly of the lobular type and the
      differential diagnosis from a primary gastrointestinal malignancy can be
      difficult. A wider knowledge of gastrointestinal metastases from primary breast
      carcinoma is important because an appropriate management allows a long survival
      period.

PMID- 8280301
TI  - [Diffuse sclerosing papillary carcinoma of the thyroid. Report of a case].
AB  - The authors report the case of a 12-year-old girl presenting with a diffuse
      sclerosing papillary carcinoma of the thyroid. The diagnosis was made on a total
      thyroidectomy specimen three months after thyroid enlargement was detected. This
      child had previously been treated medically for thyroiditis because of an
      enlarged thyroid gland with serum antithyroid autoantibodies. A few cases have
      been described in the literature. Six morphologic findings define this variant of
      papillary carcinoma: a diffuse growth pattern involving one or both lobes of the
      thyroid, prominent fibrosis, heavy lymphocytic infiltration with germinal
      centers, large numbers of psammoma bodies, squamous metaplasia and papillae
      within cleft-like tissue spaces. Some authors stated that this variant has a
      poorer prognosis than the usual papillary carcinoma of the thyroid. However, in
      some series a few patients survive without local recurrence or distant metastasis
      at a mean follow-up period of more than 10 years. Immunohistochemical studies
      have shown high accumulation of S-100 protein positive dendritic cells. Such an
      infiltration has been correlated with a better prognosis.

PMID- 8280302
TI  - [Presentation of a grid for computer analysis for compilation of histopathologic
      lesions in chronic viral hepatitis C. Cooperative study of the METAVIR group].
AB  - The METAVIR group, including 10 pathologists with a specialization in liver
      pathology, has been formed in order to discuss on problems related to chronic
      viral hepatitis C. Cooperative studies have been planed. At first, observer
      variation in the assessment of features of chronic viral hepatitis C has been
      performed. This study has led to the proposal of a coded form for pathological
      features in liver biopsy of chronic viral hepatitis C. This form will be used to
      study a large number of biopsies from patients included in clinical trials. In
      the next future, the prevalence of every of these elementary features will be
      assessed, as well as correlations between clinical, biological and pathological
      data.

PMID- 8280303
TI  - [Computer-assisted graphics software in pathology reports].

PMID- 8280304
TI  - [Malacoplakia vesicae, a rare cause of non-lithiasic cholecystitis. Report of a
      case].

PMID- 8280305
TI  - [Pancreatic heterotopia in the gallbladder. Report of a case].

PMID- 8280306
TI  - [Fulgurant regeneration after fulminant hepatitis. Report of a temporary
      orthotopic auxiliary graft in a child].

PMID- 8280307
TI  - [A kidney tumor not to be disregarded].

PMID- 8280308
TI  - [Diagnosis of a tumor of the vault of the palate].

PMID- 8280309
TI  - [Classification of tumors of the esophagus and stomach (WHO 1990). Part II:
      tumors of the stomach].

PMID- 8280310
TI  - Error and data coding in the multi-dimensional analysis of human movement
      signals.
AB  - This paper discusses two main problems of human motion data: their uncertainty
      and analysis. Considering the first point, a simulating method is proposed to
      assess the error. This approach is applied to a joint angle, computed from the
      positions of points obtained through a three-dimensional video-computer system.
      Considering the second point, a multi-variate methodology based on appropriate
      data coding and the correspondence factor analysis method is proposed. The
      outcomes of this allow the relations within the time windows of the variable set,
      the distances within the observation set and the correspondences between these
      two sets to be shown graphically. To illustrate this approach, two examples are
      considered: the analysis of the low back-pelvis angle in an ergonomical study
      about the sitting posture and the analysis of joint angles in the gait.

PMID- 8280311
TI  - Recommendations with respect to the improvement of lubricating qualities of
      synovial fluid in artificial joints.
AB  - This paper gives a short description of the lubricating properties of yellow and
      red bone marrow taken from a femur of a cadaver. The experiments have been
      conducted on a 'ball-on-plate' model. The balls were made from steel 100 CR6
      (German) and the plates were made from the same steel and ultra-high molecular
      weight polyethylene (UHMWPE, German 'Herulen'). The friction coefficients under
      loads of 50 and 300 N were determined with different combinations of friction
      components. It has been found that the lubricating properties of yellow and red
      marrow have advantages over synovial fluid. In the light of these results the
      author develops a new approach to the design of a new hip endoprosthesis.

PMID- 8280312
TI  - Parametric modelling of a knee joint prosthesis.
AB  - This paper presents an approach for the establishment of a parametric model of
      knee joint prosthesis. Four different sizes of a commercial prosthesis are used
      as an example in the study. A reverse engineering technique was employed to
      reconstruct the prosthesis on CATIA, a CAD (computer aided design) system.
      Parametric models were established as a result of the analysis. Using the
      parametric model established and the knee data obtained from a clinical study on
      21 pairs of cadaveric Asian knees, the development of a prototype prosthesis that
      suits a patient with a very small knee joint is presented. However, it was found
      that modification to certain parameters may be inevitable due to the uniqueness
      of the Asian knee. An avenue for rapid modelling and eventually economical
      production of a customized knee joint prosthesis for patients is proposed and
      discussed.

PMID- 8280313
TI  - An isoelastic prosthesis using a new composite material.
AB  - A new particulate composite material has been assessed with regard to the design
      of an 'isoelastic' or 'modulus matched' hip prosthesis. Three different prototype
      designs were assessed, each of which consisted of a femoral component made from
      the composite material, attached to a metal ball via a metal 'spike' insert. The
      prototypes varied in terms of the detailed shape of the spike, which was modified
      in the light of photoelastic stress analysis, so as to produce a more acceptable
      stress distribution to the composite material in the proximal region. Prototypes
      were made by hand moulding and by transfer moulding; both methods produced
      defects of various kinds. Simulation tests were conducted using a model of the
      proximal femur constructed from glass fibre composite, cyclically loaded in a
      servo-hydraulic testing machine. Though some difficulties were experienced with
      defective mouldings, especially for the transfer moulding process, a clear
      improvement was demonstrated for the final (Mark III) design. The fatigue
      endurance of this prototype was similar to that of conventional metal prostheses
      tested under similar conditions. Fatigue crack propagation tests were carried out
      on samples of the composite material to establish its propagation threshold.
      These results were combined with a finite element stress analysis and fracture
      mechanics theory to estimate the critical crack length for fatigue in this
      prosthesis. It was thus possible to specify the maximum safe size of defect that
      could be tolerated in use.

PMID- 8280314
TI  - Some problems in using a polyvinylidene fluoride transducer for the intra
      articular determination of joint contact stress.
AB  - A piezoelectric transducer and associated instrumentation were developed and
      evaluated as a means of experimentally determining joint contact stress. Each
      transducer, fabricated from a polyvinylidene fluoride film, comprised four
      discrete sensing elements. Following dynamic calibration of all sensing elements,
      in vitro evaluations were performed with transducers positioned in canine tibio
      femoral joints. Quantitative measurements of contact stress as a function of time
      were obtained using these transducers, the magnitudes of which ranged between
      0.01 and 7.99 MPa. Limitations associated with the transducer material and its
      use in this specific application included calibration variability and temporal
      phase shift of the transducer output signal relative to the applied load.

PMID- 8280315
TI  - Biomechanics of sports and sports injuries.

PMID- 8280316
TI  - A method for the kinematic evaluation of the knee following anterior cruciate
      ligament injury and reconstruction.
AB  - A quantitative method for assessing the kinematics of the knee in the sagittal
      plane has been developed in order to evaluate the role of the anterior cruciate
      ligament following injury and reconstruction. Measurements were made on a series
      of lateral radiographs obtained at different angles of flexion with the limb
      weight-bearing and the foot and ankle rotated so that the condyles of the femur
      overlapped. The kinematics of the joint were then defined by recording the path
      of the tip of the medial tibial spine as flexion proceeded, using a coordinate
      system based on the femur. This method overcomes the problems inherent in
      quantifying knee kinematics by using the pathway of the centre of rotation. In an
      amputated knee, tibial positions could be specified to within approximately 1.2
      mm. There were no significant differences between results obtained at the
      beginning and end of a six month period for the normal knees of two patients; the
      standard deviation of the measured tibial positions was approximately 1.6 mm.

PMID- 8280317
TI  - Skeletal accelerations measured during different exercises.
AB  - Exercise is often suggested as a means of reducing the effects of osteoporosis in
      post-menopausal women. In response to an increase in physical activity, bone mass
      can be increased and several studies have investigated the effectiveness of
      different exercises in increasing bone mass. In this study we have attempted to
      quantify the effect of different exercises by measuring the accelerations
      produced during various exercises. Accelerations have been measured at the ankle
      of normal subjects during a series of impulsive (walking, running and walking up
      and down stairs) and non-impulsive (cycling) exercises. Accelerations were
      measured using an accelerometer attached to a stiff cuff which straps around the
      ankle. Signals from the accelerometer are amplified and recorded using a
      specially developed portable data-logging system. THe principal parameters
      measured were the maximum change of acceleration (peak to peak) and the rate of
      change of acceleration. From the results it was observed that running and walking
      up and down stairs produced the highest peak-to-peak change (running = 8.08 g;
      walking downstairs = 8.11 g) and rate of change of acceleration (running = 2.14
      g/s; walking downstairs = 2.07 g/s). By contrast, a non-impulsive exercise such
      as cycling produced relatively low values of peak-to-peak change (2.24 g) and
      rate of change (0.23 g/s) of acceleration.

PMID- 8280318
TI  - Grip strength and endurance in rock climbers.
AB  - The performance of competition climbers in laboratory-based tests of pinch and
      whole hand grip strength and endurance was compared to that of non-climbers of
      the same age, sex and physique. Climbers performed significantly better,
      indicating higher stresses acting in the flexor mechanism, possibly predisposing
      injury. Attempts were made to correlate the performance in the tests to climbing
      achievement, measured by current technical climbing standards. Although pinch
      grip strength increased with the length of climbing experience, there was no
      evidence that strength in the hands alone guarantees success in competition
      climbing.

PMID- 8280319
TI  - A biomechanical analysis of the plantar surface of soccer shoes.
AB  - The incidence of severe injuries for soccer players may lead to long-term
      inactivity or, at worst, retirement from the game. Many of these injuries,
      particularly those involving the lower leg, can be attributed to adverse physical
      conditions at the interface between the soccer shoe and the playing support
      surface. This study investigated the biomechanical characteristics at this
      interface for a range of proprietary soccer shoes. An experimental system was
      designed and developed which, via a weighted pendulum arm making contact with a
      vertical column, provided controlled rotation of the forefoot of the soccer shoe
      on samples of playing surfaces. The overall rotation was found to depend on
      several physical and material factors. For example, the size 7 soccer shoes
      produced a statistically significant increase in axial rotation for the same
      impact energy compared to the larger sized shoes under test. In addition, flat
      soled shoes, designed for synthetic playing surfaces, produced consistently
      smaller rotations than shoes with either moulded or screw-in studs, although this
      finding depended on the moisture content of the playing surface. The pressure
      distribution within several soccer shoes was also measured using the F-Scan Gait
      Analysis System, for a subject walking across a grass surface. Results indicated
      differences in pressure distribution over the first metatarsal area of the foot,
      in existing shoe designs.

PMID- 8280320
TI  - Case report: arthroscopic repair of a type IV SLAP lesion--the red-on-white
      lesion as a component of anterior instability.
AB  - This case report presents a rationale and technique for repair of a vascularized
      red-on-white bucket-handle tear of the glenoid labrum and intraarticular biceps
      tendon [type IV superior labrum anterior-to-posterior (SLAP) lesion]. This lesion
      may occur as a component of anterior instability, and as such it demands repair
      at the same time as anterior surgical stabilization for instability.

PMID- 8280321
TI  - Endoscopic carpal tunnel release: a comparison of two techniques with open
      release.
AB  - Proponents of endoscopic carpal tunnel release claim less pain and scar
      tenderness, quicker recovery of strength, and earlier return to work and daily
      activities over open methods to release the transverse carpal ligament. This
      single-center prospective study is the first to compare three different treatment
      methods: standard open release, a single-portal endoscopic technique (Agee), and
      a two-portal endoscopic technique (Chow). Two hundred eleven releases in 163
      patients were evaluated by clinical outcomes questionnaire and objective testing
      over a 6-month follow-up period. There was no difference in resolution of
      paresthesias or nocturnal pain between treatment methods. Patients treated with
      open release reported more thumb weakness and pain with activities of daily
      living after surgery. Endoscopically treated patients achieved faster recovery of
      grip and pinch strength and wrist range of motion. Patients treated
      endoscopically had less mid-palm tenderness than did patients treated via the
      open technique, and Agee patients had less distal palmar tenderness than did
      patients treated via other methods. Overall, and in the workers' compensation
      group, patients treated endoscopically returned to work sooner. In the non
      workers' compensation group, Agree patients returned to work sooner than did
      patients treated via the other two methods.

PMID- 8280322
TI  - Anterior cruciate ligament fascia lata allograft reconstruction: progressive
      histologic changes toward maturity.
AB  - Biopsy samples were obtained arthroscopically from 21 patients who had undergone
      anterior cruciate ligament (ACL) reconstruction using rolled, freeze-dried fascia
      lata allograft in order to evaluate progressive histologic changes toward
      maturation. The study period was 3-20 months postoperation. The mean age (+/-
      SEM) was 31.9 +/- 10.3. Histomorphometry was used for quantitative evaluation.
      Arthroscopic examination showed fully synovialized allografts in all patients.
      Varying degrees of degenerative tissues were observed histologically. There was a
      significant, direct correlation between the percentage of polarized tissue and
      the maturity of the biopsy specimen (r = 0.9; p < 0.04). The mean area of
      polarization in the postrehabilitation period (10-20 months) was significantly
      higher (p < 0.01) than in the rehabilitation period (3-20 months). Overall, there
      was a progressive decrease in cellularity and vascularity as the allograft
      matured. Compared with the biopsy samples of normal ACLs, the allograft was still
      undergoing maturation 20 months postoperatively.

PMID- 8280323
TI  - Comparison of perioperative morbidity of anterior cruciate ligament autografts
      versus allografts.
AB  - We present a retrospective report of 50 patients (31 autograft and 19 allograft
      patients) who underwent arthroscopic bone-patellar tendon-bone anterior cruciate
      ligament (ACL) reconstructions between August 1988 and September 1990. All
      patients were followed for a minimum of 2 years. The purpose of this study was to
      analyze each group regarding hospital stay, swelling, thigh atrophy, laxity,
      strength, endurance, range of motion, patellofemoral symptoms, and complications.
      We found no statistical difference between autograft or allograft ACL
      reconstructions with regard to perioperative morbidity.

PMID- 8280324
TI  - The value of intraoperative isometry measurements in anterior cruciate ligament
      reconstruction: an in vivo correlation between substitute tension and length
      change.
AB  - With the objective to evaluate an "isometry" measurement in an anterior cruciate
      ligament (ACL) substitute, in vivo measurements were taken on 10 patients
      undergoing reconstruction due to chronic ACL deficiency. Change in intraarticular
      length of a 1.2-mm test ligament, measured with an isometer, was correlated to
      the tension created in the same test ligament after fixation, measured with a
      piezoelectric load cell. The knee was passively moved through the 0-100 degrees
      range with the patient under general anaesthesia. Good statistical and visual
      correlations between length change and tension curves were found in individual
      knees. A correlation between total length change and maximum tension, for all
      knees grouped, was also found. Individual knees showed large variation in ability
      of the tissue to absorb load, resulting in a wide range of N/mm ratios between
      length and tension. Three knees with an isolated ACL injury all showed the least
      length change, implying a better restoration of kinematics in the absence of
      associated injuries. In nine of 10 knees the length change pattern could be used
      to identify the location of the femoral drill channel, as determined on an
      intraoperative lateral projection of the knee. Intraoperative isometry
      measurement can be used to predict the tension pattern in the reconstructed knee,
      but not the magnitude of tension. It will be useful to the surgeon in avoiding an
      anterior femoral ligament insertion site, which might threaten the integrity of
      the graft by tension rise in flexion.

PMID- 8280325
TI  - Fluoroscopic assist in anterior cruciate ligament reconstruction.
AB  - When creating the femoral tunnel during endoscopic anterior cruciate ligament
      reconstruction, the potential exists for penetration of the posterior femoral
      cortex. In addition, during placement of the proximal fixation screw, the screw
      can deviate from its intended path. We have used an image intensifier
      intraoperatively to obtain a lateral view of the knee to enable the assessment of
      tunnel placement and screw alignment. This technique assures the accurate
      placement of the tibial and femoral tunnels and helps avoid screw divergence from
      the graft.

PMID- 8280326
TI  - Effects of holmium:YAG laser on equine articular cartilage and subchondral bone
      adjacent to traumatic lesions: a histopathological assessment.
AB  - This study was performed to investigate the effects of holmium:yttrium-aluminum
      garnet (Ho:YAG) laser energy on articular cartilage and subchondral bone adjacent
      to traumatically created cartilage lesions in a continuous weight-bearing model.
      The 2.1-microns wavelength was delivered efficiently and precisely in hand
      controlled contact and near-contact hard tissue arthroscopic surgery in a saline
      medium. Bilateral arthroscopy was performed on normal antebrachiocarpal and
      intercarpal joints of four adult horses. One hundred twenty traumatic lesions
      were created on three weight-bearing articular surfaces with a knife, curet, or
      motorized burr. Depths of the lesions were partial and full thickness.
      Configurations of the lesions were lacerations, scrapes, and craters. Left limbs
      were used as controls. Right limb lesions were treated with various intensities
      of laser energy: 0.1. 0.16, and 0.2 J. Animals were killed at intervals of 1, 3,
      and 8 weeks. Gross microscopic anatomy was documented, and tissue sections were
      subjected to blind review by a pathologist. Mankin grading for cellularity and
      proteoglycan content was used to qualitatively evaluate cartilage response.
      Cartilage adjacent to all lesions exposed to laser energy had better cellularity
      and proteoglycan content (p < 0.05) than did corresponding controls by Mankin
      grading. Mankin grades for levels of 0.16 and 0.2 J were lower (p < 0.05) than
      were those of controls or lesions exposed to 0.1 J. There was loss of cellularity
      and necrosis in subchondral bone at higher energy levels (0.16 and 0.2 J). This
      study examined the effects of Ho:YAG laser on articular cartilage and subchondral
      bone in terms of depth of damage and healing response over time in a weight
      bearing model. Additional research to define dose-response curves for Ho:YAG
      laser treatment of cartilage and subchondral bone are indicated.

PMID- 8280327
TI  - Saline magnetic resonance arthrography in the evaluation of glenohumeral
      instability.
AB  - Sixty-five patients underwent magnetic resonance (MR) shoulder arthrography.
      Forty-eight of these patients underwent examination under anesthesia (EUA). MR
      images were retrospectively evaluated for signs felt to be imaging indicators of
      shoulder instability, including evaluation of various capsular measurements and
      the presence of glenoid labral tears, as well as Hill-Sachs fractures.
      Statistical analysis of the results showed that no correlation between capsular
      indicators with EUA-documented instability was found. However, there was a
      statistically significant correlation between the presence of a Bankart
      cartilaginous deformity (p = 0.000) and Hill-Sachs fractures (p = 0.022) with EUA
      documented instability. Sensitivity to labral tears was 89% and specificity was
      98%, whereas Hill-Sachs fracture detection was 69% and 87%, respectively. We
      believe that MR saline arthrography is of benefit in the evaluation of the
      anterior labrum when unenhanced MR imaging is inconclusive, and we speculate on
      the role of MR arthrography as a primary investigative tool.

PMID- 8280328
TI  - The results of arthroscopic debridement of glenoid labral tears based on tear
      location.
AB  - A retrospective, average 2-year review of 14 patients with a primary glenoid
      labral tear treated by arthroscopic debridement was conducted to evaluate the
      long-term results of labral debridement based on tear location in preoperatively
      stable shoulders. All patients with concomitant pathology requiring an additional
      open or arthroscopic procedure were eliminated from this study. Every patient
      complained of shoulder pain mainly with overhead activities and nine patients
      (64%) also described "clicking" with shoulder movement. All shoulders were stable
      to translation in all quadrants during the preoperative examination and
      examination under anesthesia. The functional results at 6 months' follow-up were
      93% excellent or good. However, the results at > 1 year's follow-up (average 2
      years) were only 71% excellent or good, with a statistically significant 50% of
      patients decreased in function. The best results were in the superior and
      anterior-inferior regions. Three patients with large anterior-superior lesions
      (60%) developed postoperative instability noted at > 6 months postsurgery,
      representing a significant difference between groups. One of these patients was
      able to regain a good functional result with rotator cuff strengthening therapy.
      Close observation of patients after large anterior-superior labral tear
      arthroscopic debridement is advised because they are at risk for the delayed
      onset of instability.

PMID- 8280329
TI  - Multicompartmental pressures in the knee joint during arthroscopy.
AB  - It is well known that fast changes of position of the knee joint cause high
      instantaneous intraarticular pressures. During arthroscopy, rotation and flexion
      of the leg can create a closed-off compartment, increasing the risk of capsular
      rupture. To evaluate the risk of compartmentation, a study has been conducted in
      which the intraarticular pressure in 12 knee joints of three women and nine men
      was measured with Myopress catheters (ATOS Medical AB, Horby, Sweden) located in
      the suprapatellar pouch, and the anteromedial and the posteromedial recesses
      during arthroscopy. This study showed that a starting pressure of 100 mm Hg
      causes a significantly higher peak pressure than does 75 mm Hg. The pressure
      varies simultaneously in all compartments without signs of local compartmentation
      in any position of the joint within the range of 0-90 degrees of flexion. With a
      positive pressure in the knee joint, no compartmentation occurs within the
      suprapatellar pouch or anteromedial posteromedial compartments during an
      arthroscopic procedure.

PMID- 8280330
TI  - The synovial response after CO2 laser arthroscopy of the knee.
AB  - The CO2 laser is a precision surgical laser because of its high degree of
      absorption in soft tissue with limited lateral damage. The tissue, which absorbs
      the CO2 laser energy, and has a high water content, will be converted to vapor
      with a small residue of ash and a by-product of heat. The laser can only be
      effective if these by-products, i.e. vapors, heat, and carbon ash residue, are
      not injurious and are well tolerated by the joint. These by-products must be
      either reabsorbed by the synovium or remain as a nonviable substance in the
      joint. From April 1989 through April 1990, 40 patients underwent 43 operative
      arthroscopies of the knee using the Pfizer CO2 laser. All procedures were
      chondroplasties, synovectomies, and/or meniscectomies. All accessible CO2 carbon
      ash residue was removed from the joint after the procedures using an
      intraarticular shaver and hand rasp. Postoperatively there were no cases of
      hemorrhagic effusions, subcutaneous emphysema, or synovitis. Histologic
      examinations performed on 10 patients undergoing subsequent surgery showed no
      evidence of carbon ash residue or synovitis seen grossly or microscopically. The
      carbon ash residue is not noxious to the joint and is completely removed from the
      joint, presumably by the synovial response.

PMID- 8280331
TI  - Arthroscopic debridement after intraarticular low-velocity gunshot wounds.
AB  - An unexpected degree of joint contamination was detected during arthroscopic
      debridement of three intraarticular, low-velocity gunshot wounds to the knee.
      When bullet wounds traverse a joint, it is recommended that clothing be inspected
      for fabric defects and that arthroscopy be considered for the surgical
      debridement.

PMID- 8280332
TI  - Effect of varying angles on the pullout strength of interference screw fixation.
AB  - Arthroscopically assisted reconstruction of the anterior cruciate ligament
      deficient knee using a bone-patellar tendon-bone graft is a new and evolving
      technique. One technically demanding aspect involves the placement under
      arthroscopic visualization of the femoral interference screw. The effect on
      pullout strength of changing the angle of the interference screw from 0 degree to
      10 degrees, 20 degrees, or 30 degrees with respect to the bone plug was examined.
      The mean pullout strengths were 621 +/- 82, 594 +/- 48, 508 +/- 66, and 485 +/-
      62 N, respectively. We concluded that there was no significant difference in the
      tensile strength provided by interference screw fixation for angles up to 10
      degrees, but that there was a significant (p = 0.0010) weakening of fixation for
      screw angles > or = 20 degrees.

PMID- 8280333
TI  - The role of arthroscopy in the assessment and treatment of tibial plateau
      fractures.
AB  - This retrospective study compared arthroscopic treatment of certain tibial
      plateau fractures to traditional open techniques. From January 1989 through
      August 1992, 40 patients with tibial plateau fractures were evaluated. After
      reviewing the records and radiologic studies, 23 patients were included in the
      study based on fracture patterns. Using Hohl's revised classification system,
      patients with either local compression or split compression fractures were
      included. Twelve of these patients were treated with arthroscopic reduction and
      percutaneous fixation (ARPF; group A). The remaining 11 underwent open reduction
      and internal fixation (ORIF; group B). The results of the ARPF group were
      superior to those of the ORIF group. In the ARPF group, all reductions were
      anatomic and remained fixed at least 3 months postoperatively, whereas only six
      (55%) of the ORIF patients had anatomic reductions initially. Furthermore, one of
      these patients had further loss of reduction on follow-up radiographs. Iliac
      crest bone graft was used in two patients in group A and 10 in group B. The use
      of bone graft in the arthroscopically treated group had no effect on the final
      outcome. The average length of postoperative hospitalization for the ARPF
      patients with isolated tibial plateau fractures was 5.36 days compared with 10.27
      days for patients who were treated with ORIF. Average time to full weight bearing
      was 8.95 weeks in the ARPF group and 12.30 weeks in the ORIF group. No patients
      in either group had medial collateral ligament repairs. No ARPF-treated patients
      experienced valgus laxity after treatment. One patient in the ORIF group had
      residual instability and another walked with a cane.(ABSTRACT TRUNCATED AT 250
      WORDS)

PMID- 8280334
TI  - Arthroscopic treatment of meniscal cysts.
AB  - Historically meniscal cysts have been treated with either an open total
      menisectomy, isolated cyst excision, or a combination of the two procedures. The
      advent of arthroscopic techniques has led to innovative treatment options for
      meniscal cyst management. A review of meniscal cysts and the results of
      arthroscopic treatment form the basis of this study. From 1986 to 1991, 18
      patients with meniscal cysts were treated by arthroscopic cyst decompression.
      Thirteen men and five women comprised the study group and had an average age of
      28 years. The follow-up period ranged from 6 to 60 months (average 26). Eight of
      the cysts were medial and 10 were lateral. A horizontal cleavage tear was noted
      in all cases, and 15 partial and three subtotal menisectomies were performed in
      conjunction with an intraarticular cyst decompression. There have been no
      recurrences to date, and all patients returned to their previous level of
      activity. Parameniscal cysts may result from synovial fluid tracking through a
      horizontal cleavage tear. Successful treatment of the meniscal cyst must include
      appropriate management of the torn meniscus, which can be entirely arthroscopic,
      consisting of a partial or subtotal meniscectomy, identification of the cyst
      opening, and cyst decompression.

PMID- 8280335
TI  - Localized pigmented villonodular synovitis presenting as a loose body in the
      knee.
AB  - Localized pigmented villonodular synovitis is a rare condition of the knee that
      can present with symptoms suggesting internal derangement. We report a case of a
      patient who presented with signs and symptoms of a loose body in the knee. The
      lesion was treated with resection using arthroscopic cautery.

PMID- 8280336
TI  - Arthroscopic synovectomy in sarcoid synovitis.
AB  - Chronic synovitis is an unusual manifestation of sarcoidosis but may be
      significantly disabling. Arthroscopic synovectomy can provide an excellent
      result, relieving discomfort and arresting the disease process, and should be
      considered in any patient whose synovitis has not responded to medical
      management.

PMID- 8280337
TI  - Arthroscopic treatment of synovial chondromatosis of the shoulder and biceps
      tendon sheath.
AB  - We present a case of synovial chondromatosis of the shoulder in a 22-year-old
      man. The patient was initially treated with arthroscopic debridement and partial
      synovectomy of the shoulder joint. Eighteen months later, the patient returned
      with similar symptoms. However, repeat radiographic studies showed involvement of
      both the shoulder and biceps tendon sheath. The patient was taken back to the
      operating room for an arthroscopic debridement of the shoulder joint and
      debridement of the biceps tendon sheath through an open approach. Use of the
      arthroscope to evaluate and treat this patient allowed him to return to normal
      activities much sooner than a formal open synovectomy would have allowed.
      Additionally, the morbidity associated with arthroscopic techniques is much lower
      than that of open procedures. In cases of synovial chondromatosis, the results in
      terms of efficacy and recurrence rates of each method appear comparable.

PMID- 8280338
TI  - A technique for arthroscopic mattress suture placement.
AB  - Many techniques and instrument systems have been developed for performing
      arthroscopic Bankart repair and arthroscopic rotator cuff repair. These
      procedures often use multiple simple sutures placed in the repaired tissue. The
      use of a mattress suture design allows for inversion or eversion of the repaired
      tissue, greater repair strength, and provides a greater area of soft tissue
      apposition to bone. Described is a technique for arthroscopic mattress suture
      placement. We have used this technique primarily for arthroscopic Bankart repair
      and arthroscopic rotator cuff repair. Suture material of any type may be used
      with this technique.

PMID- 8280339
TI  - [A comparison of the two anticholinergic agents atropine and glycopyrrolate
      during antagonism of a muscle relaxation with pyridostigmine].
AB  - Central, peripheral and cardiac side-effects of both anticholinergic drugs
      atropine and glycopyrrolate were compared during the antagonism of muscle
      relaxation with pyridostigmine. In a randomized, double-blind fashion 50 patients
      were given 10 micrograms/kg of atropine and 50 were given 5 micrograms/kg of
      glycopyrrolate with 125 micrograms/kg pyridostigmine intravenously. Continuous
      Holter ECG-monitoring over 3 hours was performed. The procedure was divided into
      the following phases: control (5 minutes before application of antagonists),
      phase I (application of antagonists and the following 5 minutes), phase II
      (subsequent 30 minutes), phase III (until 3 hours had passed). The first 32
      minutes were subdivided into periods of 4 minutes. Analysed were: 1st: The number
      of patients with supraventricular, junctional and ventricular beats, 2nd: The
      mean heart rate per period, 3rd: The incidence of central-anticholinergic
      syndromes and the peripheral antimuscarinic side-effects. Supraventricular beats
      were found after atropine in 42 patients and after glycopyrrolate in 18 patients
      (p < 0.001). The differences mainly occurred during phase I (atropine 15 vs.
      glycopyrrolate 4 p < 0.05) and III (atropine 38 vs. glycopyrrolate 18, p < 0.01).
      Junctional beats were found after both drugs (atropine 7 vs. glycopyrrolate 10),
      above all during phase III. Ventricular beats were observed after atropine (21)
      and glycopyrrolate (18). Atropine as well as glycopyrrolate caused an increased
      heart rate within the first 4 minutes (atropine 47% vs. glycopyrrolate 27%, p <
      0.01). During phase III after atropine, the heart rate decreased below the
      control value (p < 0.05). None of the patients showed central anticholinergic
      syndromes after either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280340
TI  - [Anesthesia before and after curare].
AB  - Before the advent of curare, muscular relaxation essential for upper abdominal
      and intrathoracic surgery adequate operating conditions, could only be provided
      by deep ether or cyclopropane anaesthesia. The required depth of anaesthesia
      frequently caused severe cardiovascular depression, metabolic and respiratory
      acidosis and alteration of kidney and liver function. Ether, and especially
      cyclopropane sensitized the heart to the development of arrhythmias and the
      danger of explosion was never far away. For fear of anaesthetic mortality
      essential, life saving operations were often abandoned in poor risk patients. The
      administration of anaesthesia was more an art, mastered by relatively few, than a
      science that could be taught to many. It is a tribute to the early masters of
      anaesthesiology that they were able to carry their patients through the dangers
      associated with the provision of anaesthesia for major surgical procedures, with
      relatively low morbidity and mortality. The introduction of curare into
      anaesthetic practice, by Griffith and Johnson, in 1942, caused profound changes
      in the efficacy and safety of anaesthesiology. It made possible the development
      of true balanced anaesthesia, and the elimination of the explosive inhalation
      anaesthetics and the profound metabolic disturbances associated with their use.
      The concept of "inoperability," due to severe pathology or extremes of age became
      obsolete. It would be hard to envisage how open heart, organ transplant and
      radical brain and cranio-facial surgery could have developed without muscle
      relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280341
TI  - [The importance of PaO2 and PaCO2 values in the perioperative care of geriatric
      patients].
AB  - Because of the generally accepted operability of patients without any age limit
      nowadays, more information is needed about functional disorders of organs, for
      example of the lung in old age. The preoperative PaO2 value at rest in 120
      patients due to undergo urological operations (average age 77.7 +/- 4.6 years)
      was determined as 81.81 +/- 8.63 mmHg. The PaO2 values corresponding to age were
      significantly higher than the reference values in literature. During
      cholecystectomy the respiratory volume per minute at an FECO2 of 4.5 vol.% was
      measured as 6.6 +/- 1.41 l/min in 54 patients with an average age of 68.7 +/- 5.8
      years. There was no correlation with any anthropometrical data. Considerable
      fluctuations in the respiratory volume per minute make the measure of FECO2 and
      PaCO2 necessary. In old age the cerebral blood flow rate depends on PaCO2, so
      that a normocapnia is of particular importance. Similar results were found in 20
      traumatologic patients aged over 80, i.e. there were considerable differences
      between tabular values and capnometrically controlled respiratory volume per
      minute. The blood gas values were measured in 50 patients over 65 years old in
      the immediate postoperative phase of cholecystectomy. Compared with initial
      values, there was a significant decrease in PaO2 at 5, 15 and 25 minutes after
      the operation with values at 8.22 +/- 1.83 kPa, 8.24 +/- 1.83 kPa and 8.15 +/-
      1.75 kPa. These values were 27% under the preoperative values. No clinically
      discernible hypoxia occurred. The results support the demand that geriatric
      patients be given suitable attention and adequate monitoring to avoid
      complications due to the restricted compensationability of the organs and lungs.

PMID- 8280342
TI  - The mission of therapeutics.
AB  - Gerald Klerman's career as a researcher was marked by a strong interest in mood
      disorders. He was particularly interested in pathways to depressive episodes and
      their treatment. In this lecture entitled "The Mission of Therapeutics," the
      emphasis is placed on the integration of two developmental pathways representing
      biologic/genetic factors and psychosocial/environmental factors. Recent work on
      the role of childhood adversity and current stressors is reviewed, as well as
      biologic pathways and correlates. Finally, using treatment outcome as a window on
      pathogenesis is suggested as a strategy for understanding the interaction of
      biologic and psychosocial parameters in the onset of and recovery from episodes
      of depressive illness.

PMID- 8280343
TI  - Brief presentation of the story and present status of studies of the vertebrate
      cholinergic system.
AB  - This year marks the seventieth anniversary of Otto Loewi's demonstration of
      chemical transmission generally and autonomic cholinergic transmission
      specifically and the fortieth anniversary of John Eccles's proof of the existence
      of central cholinergic transmission. Following these epochal findings, the
      subsequent studies of the cholinergic system led to discoveries of similarly
      important phenomena. This review concerns these phenomena, including chemical
      structure and molecular biology of cholinergic receptors; electrophysiologic and
      ionic aspects of pre- and postsynaptic cholinergic events; the quantal expression
      of cholinergic postsynaptic events and activities of their subunits, the
      elementary events; second messengers and G proteins; synthesis, storage and
      release of acetylcholine; cholinesterases, anticholinesterases, and war gases;
      central cholinergic pathways; central cholinergic functions, behaviors,
      cholinergic EEG and REM sleep; cholinergic ontogeny and teratology; trophic
      phenomena; and the clinical aspects of the cholinergic system. This review refers
      to the history as well as the present status of each of these phenomena;
      furthermore, it describes briefly the nineteenth-century work with calabar bean,
      pilocarpine, muscarine, and nicotine, that is, the work performed before the
      promulgation of the cholinergic era.

PMID- 8280344
TI  - Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.
AB  - The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor
      snacks characterizes the overeating of obese CHO cravers, premenstrual women,
      patients with Seasonal Affective Disorder, and former smokers. This specific
      appetite for CHOs may involve brain serotonin, as the synthesis and release of
      this neurotransmitter can increase following consumption of CHO-rich foods. To
      examine whether weight loss produced by serotoninergic drugs involves a selective
      reduction in CHO intake, obese females who consumed at least 30% of their daily
      calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg
      b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly
      weight loss for 25 of 29 PL completers was 0.22 kg +/- 0.06 (mean +/- SEM); for
      21 of 28 DF completers, 0.56 +/- 0.08 kg; and for 18 of 30 FL completers, 0.58 +/
      0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF
      subject withdrew from the study due to side effects; other withdrawals were due
      to intercurrent illness or personal problems. Prior to treatment, subjects
      consumed over 40% of their daily CHO intake from snacks. Both of the drugs
      selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased
      meal CHO intake (p < .025). These results suggest that weight loss following
      treatment with serotoninergic drugs may relate to a selective decrease in CHO
      appetite.

PMID- 8280345
TI  - Naltrexone-buprenorphine interactions: effects on cocaine self-administration.
AB  - An opioid mixed agonist-antagonist analgesic, buprenorphine, significantly
      reduces cocaine self-administration by rhesus monkeys, but the relative
      contribution of buprenorphine's agonist and antagonist properties to this effect
      is unclear. This study examined the effects of concurrent treatment with
      naltrexone, a long-acting mu opioid antagonist, on buprenorphine's effects on
      cocaine and food self-administration by five rhesus monkeys. Cocaine (0.5 mg/kg
      per injection) and food self-administration (1 gm banana pellet) were maintained
      on a second order fixed ratio 4 (FR4) variable ratio (VR) 16:S schedule of
      reinforcement. Buprenorphine treatment alone (0.40 mg/kg/day) and in combination
      with ascending doses of naltrexone (0.05, 0.10, 0.20, and 0.40 mg/kg/day) was
      compared with naltrexone alone (0.40 mg/kg/day) and saline control treatment.
      Naltrexone was administered simultaneously or 20 minutes before buprenorphine
      administration. Each treatment condition was in effect for 10 days. Buprenorphine
      alone significantly reduced cocaine self-administration by an average of 53% in
      comparison to the saline treatment baseline (p < .01). When saline was
      substituted for buprenorphine, each monkey rapidly returned to its
      prebuprenorphine level of cocaine self-administration. Food self-administration
      in all conditions was equivalent to or significantly higher (p < .05) than food
      maintained responding during the saline baseline. When buprenorphine and
      naltrexone were administered simultaneously, naltrexone significantly attenuated
      buprenorphine's suppressive effects on cocaine self-administration (p < .05 to
      .01). When naltrexone was administered 20 minutes before buprenorphine, there was
      a significant naltrexone dose-dependent (p < .01) decrease in buprenorphine's
      reduction of cocaine self-administration in comparison to the initial saline
      baseline. These data suggest that naltrexone antagonizes the partial mu agonist
      component of buprenorphine, which may be important for buprenorphine's effects on
      cocaine self-administration. Moreover, the addition of an opioid antagonist to
      reduce illicit diversion of buprenorphine might also compromise its effectiveness
      for treatment of dual dependence on cocaine and opiates.

PMID- 8280346
TI  - Influence of the cholinergic agonist SDZ 210-086 on sleep in healthy subjects.
AB  - The administration of 1.0 mg SDZ 210-086, an orally acting muscarinic agonist,
      shortened rapid-eye movement (REM) latency, increased REM percent of sleep period
      time and the total duration of REM sleep, and decreased slow-wave sleep in 12
      healthy male subjects. The administration of 0.5 mg SDZ 210-086 had no
      statistically significant effect on sleep variables. Although the tonic
      components of REM sleep (REM duration, the REM percent of sleep period time) were
      increased, REM density percent (total) was significantly decreased due to the
      prolongation of total REM duration (in minutes) and a parallel reduction of the
      total number of eye movements. This finding is in contrast to studies using other
      cholinomimetics (i.e., physostigmine, arecoline, and RS 86) and may implicate
      different generating systems of phasic and tonic REM sleep components.

PMID- 8280347
TI  - Effects of tobacco smoking on the Hoffmann reflex.
AB  - Ten normal adult tobacco smoking volunteers 21 to 32 years of age were the
      subjects of this study. They were asked not to smoke for 12 hours prior to
      testing. The Hoffmann (H) reflex and its recovery cycle were measured before and
      just after smoking (on different days) one nonfiltered, zero, low (0.27 mg), or
      high (2.16 mg) nicotine tobacco cigarette. After smoking the nicotine-containing
      cigarettes, the subjects showed a reduction of the H reflex recovery cycle.
      Individual differences were marked. Nevertheless, the data obtained are
      consistent with evidence in animals that nicotine and tobacco smoke stimulate
      Renshaw inhibitory neurons in the spinal cord, either directly or indirectly.
      This technique provides another objective measure of the effects of tobacco
      smoking in human volunteers.

PMID- 8280348
TI  - Effects of ethanol, diphenhydramine, and triazolam after a nap.
AB  - This study assessed the capacity of a 60-minute nap to reverse the sedating and
      performance-disruptive effects of ethanol, triazolam, and Diphenhydramine. Twelve
      healthy, young men received (at 0800 to 0830) .6 g/kg ethanol and a placebo pill,
      .25 mg triazolam and ethanol placebo, 50 mg Diphenhydramine and ethanol placebo,
      and a placebo pill and ethanol placebo on each of 2 days in a Latin Square
      design. On one treatment day (at 0900 hour) subjects were allowed a 60-minute nap
      and on the other a sleep latency test (no nap). Then, sleep latency was tested
      (by Multiple Sleep Latency Test [MSLT] at 1100, 1300, 1500, and 1700) and divided
      attention performance assessed (at 1130). The nap reversed the sedative effects
      of ethanol and Diphenhydramine and reduced those of triazolam (on MSLT). The nap
      reduced the performance-disruptive effects of ethanol and Diphenhydramine but not
      those of triazolam. Given the differing neurobiological mechanisms of these
      drugs, the data suggest that some of their effects are nonspecific and result
      from activation of sleep mechanisms that a nap can reverse.

PMID- 8280349
TI  - On the marihuana attenuation of the rise of ethanol levels in human subjects.

PMID- 8280350
TI  - [From exhaustion to revolt].

PMID- 8280351
TI  - [Advice of the E.N.T specialist: research on criteria predictive of success in
      the treatment of ragweed pollinosis].

PMID- 8280352
TI  - [Advice of a pediatrician].

PMID- 8280353
TI  - [Advice of an opthalmologist: ophthalmology and ragweed allergy].

PMID- 8280354
TI  - [Advice of the allergist: some thoughts on the problems posed by ragweed in the
      middle Rhone valley].

PMID- 8280355
TI  - [Pollen counts of the A.F.E.D.A, Lyon-Bron 1992 (method of P. Cour].

PMID- 8280357
TI  - [New legislation of the Common Agricultural Policy on fallow land, its
      implications for the dissemination of ragweed].

PMID- 8280356
TI  - [Ragweed allergy in domestic carnivores: symptoms, diagnosis, treatment].

PMID- 8280358
TI  - [Ragweed pollen in France in 1992, evolution].

PMID- 8280359
TI  - [Comparison of the pollen counts in Lyon-Bron from 1989 to 1991: traps of Hirst
      (I. Pasteur), P. Cour (A.F.E.D.A)].

PMID- 8280360
TI  - Backscatter correction algorithm for TBI treatment conditions.
AB  - The accuracy requirements in target dose delivery is, according to ICRU, +/- 5%.
      This is so not only in standard radiotherapy but also in total body irradiation
      (TBI). Physical dosimetry plays an important role in achieving this recommended
      level. The semi-infinite phantoms, customarily used for dosimetry purposes, give
      scatter conditions different to those of the finite thickness of the patient. So
      dose calculated in patient's points close to beam exit surface may be
      overestimated. It is then necessary to quantify the backscatter factor in order
      to decrease the uncertainty in this dose calculation. The backward scatter has
      been well studied at standard distances. The present work intends to evaluate the
      backscatter phenomenon under our particular TBI treatment conditions. As a
      consequence of this study, a semi-empirical expression has been derived to
      calculate (within 0.3% uncertainty) the backscatter factor. This factor depends
      lineally on the depth and exponentially on the underlying tissue. Differences
      found in the qualitative behavior with respect to standard distances are due to
      scatter in the bunker wall close to the measurement point.

PMID- 8280361
TI  - A simple approach to the technical aspects of radiosurgery treatments.
AB  - An approach to radiosurgery treatment that can be readily adopted in most
      radiotherapy centers with linear accelerators is presented. In our institution, a
      Leksell-type of neurosurgical frame, a computed tomography scanner, locally
      fabricated cones, and 6 MV X-ray beams are used to perform radiosurgery
      treatments. Collimated arcs with dose distributions, that conform to the shape of
      the lesion in the transverse and the sagittal planes are used. It is argued that
      the uncertainties in the localization of the isocenter within a lesion and the
      specifications of the size of the target volume do not justify high precision
      mechanical devices for most radiosurgery treatments.

PMID- 8280362
TI  - An analysis of image segmentation time in beam's-eye-view treatment planning.
AB  - In this work we tabulate and histogram the image segmentation time for beam's eye
      view (BEV) treatment planning in our center. The average time needed to generate
      contours on CT images delineating normal structures and treatment target volumes
      is calculated using a data base containing over 500 patients' BEV plans. The
      average number of contours and total image segmentation time needed for BEV plans
      in three common treatment sites, namely, head/neck, lung/chest, and prostate,
      were estimated.

PMID- 8280363
TI  - Craniospinal irradiation for trilateral retinoblastoma following ocular
      irradiation.
AB  - A case study is presented. Craniospinal radiotherapy and a three-fold pineal
      boost for trilateral retinoblastoma were delivered to a patient previously
      irradiated for ocular retinoblastoma. The availability of CT-based three
      dimensional treatment planning provided the capability of identifying the
      previously irradiated volume as a three-dimensional anatomic structure and of
      designing a highly customized set of treatment beams that minimized reirradiation
      of that volume.

PMID- 8280364
TI  - Application of magnetic resonance imaging and three-dimensional treatment
      planning in the treatment of orbital lymphoma.
AB  - Radiotherapy for lymphoma of the orbit must be individualized for each patient
      and clinical setting. Most techniques focus on optimizing the dose to the tumor
      while sparing the lens. This study describes a technique utilizing magnetic
      resonance imaging (MRI) and three dimensional (3D) planning in the treatment of
      orbital lymphoma. A patient presented with an intermediate grade lymphoma of the
      right orbit. The prescribed tumor dose was 4050 cGy in 18 fractions. Three D
      planning was carried out and tumor volumes, retina, and lens were subsequently
      outlined. Dose calculations including dose volume histograms of the target,
      retina, and lens were then performed. Part of the retina was outside of the
      treatment volume while 50% of the retina received 90% or more of the prescribed
      dose. The patient was clinically NED when last seen 2 years following therapy
      with no treatment-related morbidity. Patients with lymphomas of the orbit can be
      optimally treated using MRI based 3D treatment planning.

PMID- 8280365
TI  - Imaging of radiation dose for stereotactic radiosurgery.
AB  - The distributions of radiation dose for stereotactic radiosurgery, using a
      modified linear accelerator (Philips SL-25 and SRS-200), have been studied by
      using three different dosimeters: (1) ferrous-agarose-xylenol orange (FAX) gels,
      (2) TLD, and (3) thick-emulsion GafChromic dye film. These dosimeters were loaded
      into a small volume of defect in a phantom head. A regular linac stereotactic
      radiosurgery treatment was then given to the phantom head for each type of
      dosimeter. The measured radiation dose and its distributions were found to be in
      good agreement with those calculated by the treatment planning computer.

PMID- 8280366
TI  - Computer-aided treatment design of a distal upper extremity soft tissue tumor
      with electron beam radiotherapy.
AB  - We present here a novel approach for the planning and treatment of a distal upper
      extremity soft tissue tumor. Utilizing computed tomography (CT) based electron
      dose calculations, a customized compensating wax bolus was designed in order to
      deliver sufficient dose coverage to the tumor volume while sparing the draining
      lymphatics of the patient's hand and digits. A clinical case is presented as well
      as the design and construction of the compensator. Outcome and clinical
      implications are discussed.

PMID- 8280367
TI  - High dose hyperfractionated radiotherapy for adults with glioblastomas.
AB  - From 1989 to 1991, 27 patients with glioblastoma multiforme or anaplastic
      astrocytoma of the brain were treated with radiotherapy. Fifteen of twenty-seven
      patients were treated through limited volume fields, with a thrice-a-day (1.1
      Gy/f) or twice-a-day (1.4 Gy/f) hyperfractionated regimen to a total physical
      dose of 62-92 Gy (median dose 76 Gy). The remaining 12 were treated with whole
      brain irradiation (40 Gy of total conventionally fractionated dose) and a
      localised boost to a total dose of 60 Gy. The hyperfractionated regimen was well
      tolerated and there was no sign of increased brain oedema to indicate the
      insertion of a split. Of six patients who received a NTD10 (normalised total dose
      for alpha/beta = 10) higher than 71 Gy, five showed CR (83% CR rate) versus three
      of 21 patients who received a lower NTD10 (14% CR rate). For 13 patients who
      received a NTD10 higher than 66 Gy, the 18-months survival was 61% (8/13) versus
      28% (4/14) for 14 patients who received a NTD10 less than 66 Gy. As far as the
      late morbidity is concerned, of six patients treated with 76-92 Gy of physical
      dose, none died because of radiation-induced brain necrosis within 18-42 months
      of follow-up, and three of them are without evidence of disease 18-31 months
      after the end of radiation treatment. None of our 15 patients who received less
      than whole brain irradiation relapsed outside the radiation portals. The present
      study strongly suggests the use of limited volume hyperfractionated radiotherapy
      schemes, so as to increase the local tumor dose (NTD10) to values higher than 79
      Gy, at the same time keeping the NTD2 (NTD for alpha/beta = 2) below 68 Gy.

PMID- 8280368
TI  - Cell division versus cell death: a functional model of multistep neoplasia.

PMID- 8280369
TI  - Effect of gastrin-releasing peptide on the pancreatic tumor cell line (Capan).
AB  - Gastrin-releasing peptide (GRP) has previously been shown to be an autocrine
      growth factor for small cell lung cancer, and our objective in the study
      presented here was to determine whether GRP has a similar role in pancreatic
      cancer. Using 125I-GRP, we demonstrated binding to specific, saturable, high
      affinity sites (Kd = 1 nM; Bmax = 245 fmol/mg protein) in membrane preparations
      from the pancreatic tumor cell line Capan. The receptors were found to be
      biologically active. In whole cells, a GRP analogue bound to these receptors and
      stimulated rapid transfer of tritium from the tritiated lipid inositol pool to
      inositol triphosphates. Exogenous GRP addition stimulated incorporation of
      [3H]thymidine into DNA 20-60%. This stimulatory effect was blocked by the
      addition of a monoclonal antibody that complexed specifically with the receptor
      binding portion of the peptide. In addition, the monoclonal antibody inhibited
      the growth of Capan cells in an in vitro growth assay without exogenous peptide.
      Bombesin receptor-specific antagonists also inhibited growth in a similar
      fashion. These data suggest that paracrine production of GRP may be important in
      pancreatic tumor growth, or that low-levels of a GRP-like peptide may play an
      autocrine role in this tumor.

PMID- 8280370
TI  - Association of tumorigenic and nontumorigenic (immunogenic) variants in a mouse T
      cell lymphoma with two distinct p53 mutations.
AB  - An in vitro model system for xenogenization has been developed in which an
      immunogenic, nonmalignant phenotype was selected from a highly malignant T-cell
      line (S49). We showed by single-strand conformation polymorphism and DNA sequence
      analysis that specific point mutations in the p53 tumor suppressor gene
      correlated with a change from a tumorigenic to a nontumorigenic (immunogenic)
      phenotype. Specifically, we found that the highly malignant S49 cell line T-60
      contains an Arg-->Gln substitution at residue 246 in exon 7 of p53. In contrast,
      nontumorigenic (immunogenic) variants (T-25-Adh and Rev-1) exhibited a Gly-->Ser
      substitution at residue 242 of p53. In two subsequent tumorigenic revertants
      derived from Rev-1, we again found the Arg-->Gln substitution at residue 246 that
      was found initially in the T-60 cells. Thus, mutation at residue 246 of p53 was
      associated with a highly malignant phenotype, whereas a novel mutation at residue
      242 of p53 appeared to be associated with a nonmalignant phenotype and may have
      actually protected the host through immunization. We conclude that mutation of
      residue 242 may represent a new class of permissive (nonmalignant) mutations in
      the mouse that are analogous to the Li-Fraumeni mutation in humans.

PMID- 8280371
TI  - Low frequency of retinoblastoma gene alterations in rat hepatocellular
      carcinomas.
AB  - Abnormalities of the retinoblastoma (Rb) gene have been reported in some human
      cancers, including hepatocellular carcinomas (HCCs). We examined by Southern
      blotting the status of the Rb gene in HCCs induced in rats in four experimental
      models. A low frequency of Rb gene alterations, detected as novel hybridizing
      bands unique to each tumor, was observed. Expression of the Rb protein product
      was examined in the HCCs and in seven established rat hepatoma cell lines
      studied. It appears, therefore, that alterations in the structure or expression
      of the Rb gene do occur but probably do not contribute in a major way to
      hepatocarcinogenesis in the rat.

PMID- 8280372
TI  - Restoration of gap-junctional intercellular communication in a communication
      deficient rat liver cell mutant by transfection with connexin 43 cDNA.
AB  - To study the biochemical basis of gap-junctional intercellular communication
      (GJIC) and its role in tumorigenesis, a mammalian cell expression vector carrying
      both a rat connexin 43 (Cx43) cDNA and an amplifiable dihydrofolate reductase
      (DHFR) gene was transfected into the GJIC-deficient rat liver mutant cell line
      aB1. Two stable transfectants were selected for further amplification of the
      transfected Cx43 gene by increasing stepwise the concentration of methotrexate
      (MTX) in the culture medium. The results indicate that GJIC was restored in these
      two Cx43 cDNA transfectants after they became highly resistant to MTX but not in
      the control-vector transfectants, in which the DHFR gene was similarly amplified.
      The amount of Cx43 DNA revealed by Southern blot analysis and the expression of
      Cx43 gene revealed by northern and western blot analyses were concomitantly
      increased in the Cx43 cDNA transfectants resistant to high concentrations of MTX.
      Western blot analysis, using an antipeptide antibody that specifically recognizes
      Cx43 protein, further revealed that an approximately 46-kDa phosphorylated Cx43
      protein that was prominent in the parental GJIC-competent cells was absent in the
      aB1 cells. This Cx43 protein, however, reappeared in the two Cx43 cDNA
      transfectants after amplification. After treatment of the membrane proteins with
      alkaline phosphatase in vitro, the approximately 46- and 44-kDa proteins
      disappeared, whereas the approximately 42-kDa proteins remained with increasing
      intensity, indicating that the higher molecular-weight proteins were the
      phosphorylated Cx43. These results indicate that a defect in posttranslational
      phosphorylation of Cx43 protein associated with low expression of the Cx43 gene
      might be responsible for the GJIC deficiency in aB1 cells and that increased
      expression of Cx43 by gene amplification might restore this phosphorylated Cx43
      protein and so reestablish GJIC.

PMID- 8280373
TI  - Carbon tetrachloride induction of rapid changes in liver nuclear protein factors
      capable of sequence-specific binding to regulatory elements in the long terminal
      repeat of polytropic-class endogenous murine leukemia virus-related proviruses.
AB  - Treatment of mice with hepatic carcinogens, including CCl4, has been shown to
      rapidly enhance the transcription of endogenous murine leukemia virus-related
      proviral sequences in the liver. To understand the mechanism for this
      transcriptional stimulation, we used nuclear protein preparations from mouse
      livers to perform DNase I protection analyses and identified nuclear protein
      binding on approximately 20 individual sequences within the regulatory regions of
      the long terminal repeat (LTR) of a polytropic-class endogenous provirus clone.
      From 3 to 144 h after treatment with CCl4, the livers of FVB/N mice were analyzed
      for specific nuclear protein binding to the LTR DNA. Three to nine hours after
      CCl4 treatment, decreased protection was seen at potential regulatory cis
      elements throughout the LTR, including specific sites within the putative
      negative regulatory element (located 5' of the consensus enhancer sequences) and
      the 3' terminal portion of the polytropic class-specific enhancer-like inserted
      sequence element and around the CCAA(C/T) box in the promoter region. In
      addition, by 3-6 h after treatment, a transient increase in protection activity
      for the transcription initiation site occurred. The loss of cis-element
      protection expanded to other binding sites and became most marked by 48 h after
      treatment. As the regenerating liver recovered, the nuclear protein binding
      activities for these LTR sequences also recovered, but protection at the TATAA
      and transcription initiation sites remained deprotected at 144 h after treatment.
      Nuclear protein protection of other sites, particularly in the conserved LTR
      enhancer sequences, was minimally affected by CCl4 treatment. Three nuclear
      protein binding sites that showed rapid CCl4-induced kinetic changes were
      homologous to the consensus sequence for the binding of the transcription factor
      families MEF-2, HNF-1, and C/EBP. The complex kinetic changes in factors that may
      contribute to the rapid and transient induction of endogenous retroviral gene
      expression in the liver after CCl4 exposure are discussed.

PMID- 8280374
TI  - Dose- and time-dependent expression of transforming growth factor-beta 1 mRNA and
      protein in mouse epidermis and papillomas after repeated topical application of
      benzo[a]pyrene.
AB  - Topical weekly application of 64 micrograms of benzo[a]pyrene (BAP) for 4 wk
      induced transforming growth factor (TGF)-beta 1 mRNA in the epidermis of Swiss
      (ICR) mice, with a maximum at 6-12 h after the last treatment. The increase in
      TGF-beta 1 mRNA concentration was accompanied by an increase in
      immunohistochemically detectable intracellularly localized TGF-beta 1 protein in
      the suprabasal epidermis and by the appearance of extracellularly localized TGF
      beta 1 in the basal layers. A dose rate of 16 micrograms/wk for 4 wk was unable
      to induce the same response. In contrast, after 20 weekly topical applications of
      16 or 64 micrograms of BAP, an increase in TGF-beta 1 mRNA concentration and the
      appearance of extracellularly localized protein in the epidermis were observed.
      These changes in TGF-beta 1 expression were paralleled by changes in epidermal
      morphology. A similar group of animals treated with 4 micrograms of BAP/wk for 20
      wk did not respond differently from untreated controls. Papillomas resulting from
      treatment with 16 or 64 micrograms of BAP/wk for 28 wk stained for
      intracellularly localized TGF-beta 1 predominantly in the differentiating and
      nondividing layers. Papillomas stained for extracellularly localized TGF-beta 1
      solely in the less differentiated and dividing cells. These results suggest that
      tumorigenesis by BAP involves the induction of cumulative changes in epidermal
      TGF-beta 1 mRNA and protein concentrations as well as alterations in skin
      morphology associated with a tumor-promotion process.

PMID- 8280375
TI  - Further analysis of c-Ha-ras mutations in papillomas initiated by several
      polycyclic aromatic hydrocarbons and papillomas from uninitiated, promoter
      treated skin in SENCAR mice.
AB  - In this study we analyzed the mutations in c-Ha-ras from skin papillomas
      initiated with benzo[a]pyrene (B[a]P), 7-methylbenz[a]anthracene (7-MBA), and 10
      fluoro-7-methylbenz[a]anthracene (10-F-7-MBA) and from papillomas induced by
      treatment with tumor promoter alone. Among the papillomas induced by treatment
      with tumor promoter alone, 56% (nine of 16) had mutations in c-Ha-ras. These
      mutations were found primarily in codon 61 and included both A182-->T and A182-
      >G mutations. In addition, one promoter-induced tumor had a G35-->A mutation in
      codon 12, and one had a G37-->C mutation in codon 13. The other promoter-induced
      papillomas did not have detectable mutations in codons 12, 13, or 61. Most of the
      B[a]P-initiated papillomas (77%; 10 of 13) did not have detectable mutations in c
      Ha-ras codons 12, 13, or 61. However, three of these B[a]P-initiated papillomas
      had c-Ha-ras codon 13 mutations; one had a G37-->C transversion and two had G38-
      >T transversions. Most of the 7-MBA-initiated tumors and all of the 10-F-7-MBA
      initiated tumors had an activated c-Ha-ras gene [nine of 10 (90%) and 11 of 11
      (100%), respectively]. These mutations were almost exclusively A182-->T
      transversions in codon 61 except for two 7-MBA-initiated papillomas that had G37-
      >C transversions in codon 13. The results suggest that more than one mechanism
      may contribute to activation of c-Ha-ras by polycyclic aromatic hydrocarbons
      (PAHs) in mouse skin. Furthermore, the absence of c-Ha-ras mutations in most
      B[a]P-initiated papillomas, as well as in a significant fraction of those induced
      by tumor promoter alone, suggests that there may be other molecular targets
      involved in tumor initiation by PAHs in mouse skin.

PMID- 8280376
TI  - Toxicity of phorbol esters for human epithelial cells expressing a mutant ras
      oncogene.
AB  - Phorbol esters and related compounds provide a promising source of potential
      anticancer agents. The mechanism of their toxicity, however, is unclear, and
      interpretation has been complicated by the conflicting responses exhibited by
      different transformed cell lines. Previously we showed that in primary thyroid
      follicular cells, expression of mutant p21ras conferred a striking sensitivity to
      the toxic effects of phorbol esters. We have now extended this work using a
      thyroid cell line with an inducible mutant ras gene to exclude the possibility
      that this result was a trivial consequence of the marked growth stimulation
      induced in these cells by mutant p21ras. Furthermore, by assessing the action of
      a panel of phorbol esters and a potential chemotherapeutic agent, bryostatin, we
      demonstrated that this phenomenon was only a function of biologically active
      phorbol esters. These results provide a molecular rationale for the development
      of phorbol ester analogues as chemotherapeutic agents.

PMID- 8280377
TI  - ras protein p21 processing enzyme farnesyltransferase in chemical carcinogen
      induced murine skin tumors.
AB  - Farnesylation of ras protein p21 is crucial for the protein's membrane
      localization, which is essential for its cell-transforming activity, which in
      turn is thought to be critical for the ultimate induction of cancer. The
      cytosolic enzyme farnesyltransferase plays a major role in posttranslational
      modification of p21, but the level of farnesyltransferase activity in mammalian
      tumors and its relationship to the processing of cytosolic p21 that leads to
      tumorigenesis are unknown. We report here that farnesyltransferase activity was
      significantly higher in chemical carcinogen-induced benign skin papillomas in
      SENCAR mice than in the epidermises of control animals. The enzyme is primarily
      epidermal in origin, and kinetic studies with cytosol from epidermis and
      papillomas showed that the reaction was linear with respect to time, substrate
      concentration, and protein content. Skin papillomas showed significantly elevated
      levels of both cytosolic and membrane-bound Ha-ras p21, whereas far lesser
      cytosolic and almost negligible amounts of membrane-bound p21 were present in the
      epidermis of control mice. There was a positive correlation between increased
      enzyme activity in papilloma cytosol and the processing of overexpressed
      cytosolic Ha-ras p21 for its localization to membrane.

PMID- 8280378
TI  - Dependence of induction of osteocalcin gene expression on the presence of wild
      type p53 in a murine osteosarcoma cell line.
AB  - The p53 gene undergoes rearrangement in a high percentage of osteosarcomas,
      resulting in loss of its expression. A p53-null murine osteosarcoma cell line F6
      was transfected with either a wild-type or a mutant p53 gene. Stably transfected
      cell lines were obtained, and their differentiation capabilities were compared in
      vitro with the parental cell line. Alkaline phosphatase and osteocalcin
      expression were measured as early and late differentiation markers, respectively.
      Induction of alkaline phosphatase expression was not affected by the presence of
      either p53 gene, whereas osteocalcin expression was seen in cells containing the
      wild-type p53 gene but not in the parental p53-null or mutant-expressing cell
      lines. That the induction of osteocalcin was intrinsically dependent on the
      presence of wild-type p53 was also indicated by the use of a temperature
      sensitive Val 135 p53 mutant at 32 degrees C; predominant expression of p53 in
      the wild-type conformation resulted in osteocalcin expression. While the wild
      type p53 gene could suppress tumor formation in vivo, the tumors expressing the
      mutant p53 gene grew two to three times as large as the tumors that did not
      express p53. Therefore, the absence of end-point differentiation in bone due to
      p53 rearrangements may contribute to the maintenance of the tumorigenic phenotype
      in osteosarcomas.

PMID- 8280379
TI  - Correlation of p53 mutations with epidermal growth factor receptor overexpression
      and absence of mdm2 amplification in human esophageal carcinomas.
AB  - Esophageal carcinomas from 24 patients, most of whom were smokers and consumed
      alcoholic beverages daily, were analyzed for mutations in exons 5-8 of the p53
      tumor suppressor gene. Mutations were identified by polymerase chain reaction
      amplification and direct sequencing in 12 of 24 (50%) of the samples; almost half
      of the mutations were at A:T base pairs. Nuclear accumulation of p53 protein,
      determined by immunohistochemistry with the CM-1 polyclonal antibody, was
      observed in all cases in which a missense mutation in the p53 gene was detected.
      None of the 24 carcinomas had amplification of the mdm2 gene, an alternate
      pathway to p53 loss of function. Alterations involving three other cancer-related
      genes associated with human esophageal carcinogenesis, c-erbB-1/epidermal growth
      factor receptor (EGFR), c-myc, and retinoblastoma (Rb), were examined by Southern
      blot or immunohistochemical analysis in the same sample set to explore the
      possibility of a link between oncogene activation and loss of tumor suppressor
      function. While no associations were observed between amplification of the c-myc
      or EGFR genes and p53 abnormalities, a significant correlation (P < 0.01) was
      seen between the presence of p53 mutation and EGFR overexpression. Absence of Rb
      protein, measured immunohistochemically, was observed in four tumors, none of
      which had aberrations of the p53 gene.

PMID- 8280380
TI  - Mutations of the p53 tumor suppressor gene and the ras gene family in
      intrahepatic cholangiocellular carcinomas in Japan and Thailand.
AB  - The incidence and pattern of mutations of the ras oncogenes and the p53 tumor
      suppressor gene have been shown to differ among different cancer types and even
      among the same cancer types with different etiological backgrounds. For example,
      in a previous study we showed that not only the etiology but also the incidence
      of point mutation of the c-Ki-ras oncogene in cholangiocellular carcinomas (CCCs)
      differ between Japanese and Thai patients. In the study presented here, we
      examined the incidence of mutations in the ras gene family and the p53 gene in
      CCCs of both Japanese and Thai patients by single-strand conformation
      polymorphism and direct sequencing analyses and compared the pattern of p53
      mutation between these two CCC groups. Although the incidence of ras mutation
      differed markedly between Japanese (seven of 12, 58%) and Thai (two of 26, 8%)
      cases, the incidence of p53 mutation was similar: four of 12 (33%) and nine of 26
      (35%), respectively. Except for one case in which deletion-insertion was detected
      in the second exon of the N-ras gene, all ras mutations occurred at codon 12 or
      13 of the c-Ki-ras gene. All p53 mutations but one were detected in a highly
      conserved region, and the predominant form of the mutations was G:C-->A:T
      transition at CpG sites in both Japanese and Thai cases, similar to that reported
      for colorectal cancers. Therefore, in contrast to the ras oncogenes, mutation of
      the p53 gene was frequently involved in the development of CCCs in both Japanese
      and Thai patients, irrespective of any difference in etiology.

PMID- 8280381
TI  - Lack of nutrition in AHCPR guideline.

PMID- 8280382
TI  - The role of magnetic resonance imaging in the evaluation of the soft tissue mass.
AB  - Magnetic resonance imaging is used widely to investigate soft tissue masses. The
      effectiveness of MRI derives from unrivaled soft tissue contrast and multiplanar
      imaging capability. Magnetic resonance spectroscopy has been used to examine the
      phosphometabolites of normal and pathological soft tissues. We review the role of
      MRI and MRS in the detection and characterization of soft tissue masses and in
      staging soft tissue malignancies. The detection of a soft tissue mass depends on
      image contrast between normal and pathological tissue. We review the salient
      factors, both intrinsic properties of tissues and parameters of MR imaging, which
      influence soft tissue contrast on an MR image. Specific pulse sequences that have
      been compared for tumor detection are discussed. One goal of a radiological test
      is to provide tissue-specific characterization. Alone or in combination, various
      MR imaging characteristics of a soft tissue mass have been studied for an
      association with benign or malignant tissue. MR imaging signs discussed in this
      review include signal intensity, relaxation time, homogeneity of signal pattern,
      septation, size at presentation, shape, margin definition, peritumoral edema,
      involvement of bone or neurovascular tissue, and contrast enhancement. The MR
      imaging appearance of hemangioma, lipoma, pigmented villonodular synovitis,
      desmoid tumor, hematoma, arteriovenous malformation, and ganglion cyst is also
      reviewed. MR imaging is the quintessential imaging method for staging a soft
      tissue malignancy. We review three staging systems in common use and the role of
      MR imaging for local staging of untreated and treated soft tissue malignancies.

PMID- 8280383
TI  - Hippocampal cell firing correlates of delayed-match-to-sample performance in the
      rat.
AB  - Hippocampal CA1 and CA3 neurons were recorded in rats performing a delayed-match
      to-sample (DMTS) task. Complex spike cells showed significant firing peaks
      following sample and match responses and during delivery of water reward.
      Individual cells were classified into 4 subtypes according to the presence or
      absence of firing in each of these 3 phases. There were significant differences
      in delay interval firing among the 4 subtypes, but firing during the delay did
      not predict the correct response: 34% of the cells showed a linear change in
      firing during the delay. Further analyses revealed significant lever position
      firing biases in approximately 70% of the cells tested irrespective of subtype.
      The complexity of firing correlates of the neurons recorded in this DMTS task
      suggests that the hippocampus divides specific aspects of the performance demands
      of the task across different cell subtypes, which together provide sufficient
      information to resolve the matching-to-sample problem on any given trial.

PMID- 8280384
TI  - Critical role of the parahippocampal region for paired-associate learning in
      rats.
AB  - Human amnesics are severely impaired in learning arbitrary associations between
      word pairs. This report examines the role of the hippocampal system in an analog
      of paired-associate learning developed for rats. Subjects with selective damage
      to the parahippocampal region and controls were tested on an odor-guided paired
      associate task. Normal rats readily learned to distinguish paired associates from
      various mispairings of the same odors, whereas most animals with parahippocampal
      damage failed to learn. Lesioned animals were, however, able to acquire correct
      responses to stimulus pairs for which an association between odors was not
      required. These findings extend the usefulness of olfactory learning as a model
      for studies of higher order learning capacity in rodents and indicate that in
      rats, as in humans, hippocampal areas are critical for learning arbitrary
      nonspatial relationships between stimuli.

PMID- 8280385
TI  - Classical conditioning after cerebellar lesions in humans.
AB  - We explored classical conditioning in human subjects who had lesions in their
      cerebellar circuitry. Seven patients with damage to cerebellar structures and
      matched control subjects underwent simple delay tone-airpuff conditioning. Eyelid
      conditioned response (CR) acquisition was severely disrupted in the patient
      group, whereas autonomic CRs and slow cortical potentials developing between
      conditioned stimulus (CS) and the unconditioned stimulus (UCS) were unaffected.
      Results are consistent with animal studies and earlier case reports indicating
      that intact cerebellar structures are necessary for the acquisition of
      classically conditioned motor responses.

PMID- 8280386
TI  - Single-unit activity in the lateral nucleus of the amygdala and overlying areas
      of the striatum in freely behaving rats: rates, discharge patterns, and responses
      to acoustic stimuli.
AB  - Acoustic responses of single units were examined in awake, freely behaving rats
      in the lateral nucleus of the amygdala (AL). Recordings were made from a movable
      bundle of 9 microwires. Most cells had very low rates of spontaneous activity
      (about 3 spikes/s average). Firing rates increased during sleep states. Short
      latency auditory responses (12-25 ms) were found in the dorsal subnucleus (ALd)
      of the AL. Cells in the ALd most typically responded in a sustained fashion. Some
      of the cells in the ALd showed preferences for high frequencies, tone bursts, or
      frequency-modulated stimuli with center frequencies above 12 kHz. Response
      latencies were considerably longer in other areas of the amygdala. Our results
      corroborate the main findings of a previous study (F. Bordi & J. LeDoux, 1992)
      that examined the acoustic response properties of single cells in the AL in
      anesthetized rats. Together the findings from awake and anesthetized rats provide
      the most precise information about sensory processing in amygdala neurons
      available to date.

PMID- 8280387
TI  - Dissociating the anti-fear effects of septal and amygdaloid lesions using two
      pharmacologically validated models of rat anxiety.
AB  - Effects of septal and amygdaloid lesions were compared in 2 models of rat
      "anxiety." Septal lesions decreased burying behavior in the "shock-probe burying
      test" and increased open-arm exploration in the "elevated plus-maze test,"
      whereas amygdaloid lesions produced neither of these anxiolytic effects. However,
      amygdaloid lesions increased rats' contacts of the electrified probe, an
      anxiolytic effect not produced by septal lesions. Each of these distinct,
      anxiolytic effects of septal or amygdaloid lesions were displayed together in
      animals with lesions of both structures. Furthermore, the magnitude of these
      anxiolytic effects after combined lesions was comparable to their magnitude after
      individual lesions. Taken together, these results suggest the amygdala and the
      septum independently control the expression of different fear-related behaviors.

PMID- 8280388
TI  - Propensity to form conditioned taste aversions augments anorexia in obese (ob/ob)
      mice with B16 melanoma.
AB  - Ob/ob mice (OB) with B16 melanoma become anorectic, but lean mice (LN) do not.
      Present studies suggest that this difference reflects a greater bent for OB to
      form conditioned taste aversions (CTA). In Exp 1, healthy OB formed stronger CTAs
      than LN to a saccharin taste paired with lithium chloride (LiCl, 3 mEq/kg ip). In
      Exp 2, the OB-LN difference of Exp 1 was decreased by giving naltrexone (10 mg/kg
      sc) before LiCl, which suggested opiate involvement. Exp 3 showed that OB tumor
      anorexia vanishes if foods dissociated from tumor growth are given: OB fed a
      constant diet became anorectic 16 days after B16 inoculation; giving a new diet
      on Day 16 delayed anorexia onset for 8 days; a second new diet on Day 32
      abolished anorexia for 24 hr. LN with tumors ate all diets at nontumor control
      levels. OB survived melanoma longer than LN regardless of diet, but OB fed a
      varied diet died first; thus, anorexia may enhance OB survival.

PMID- 8280389
TI  - Possible anatomical basis of recovery of function after neonatal frontal lesions
      in rats.
AB  - Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on
      the Morris water task on Days 19-21 or Days 56-58. The operated groups were
      equally impaired at the water task on Days 19-21, but the Day 10 rats had
      recovered by 56 days. Dendritic arborization and spine density were analyzed in
      parietal layer II-III pyramidal cells. At Day 60, but not at Day 22, the Day 10
      animals had more dendritic spines per unit dendritic length than did the controls
      or Day 1 rats. Thus, there was functional recovery rather than sparing after
      frontal lesions at 10 days, and the recovery was correlated with an increase in
      dendritic spines.

PMID- 8280390
TI  - Sexual reinforcement is blocked by infusion of naloxone into the medial preoptic
      area.
AB  - The present experiment was designed to determine whether infusions of naloxone
      into specific brain sites can block sexual reinforcement as evaluated with the
      conditioned place preference procedure. Methylnaloxonium (5 micrograms/cannula)
      was infused bilaterally either into the medial preoptic area (MPOA) or into the
      nucleus accumbens (NAC) of sexually experienced male rats. We chose the MPOA
      because it is important for sexual behavior, and several opioid peptides have
      been shown to modify sexual behavior when infused there. The NAC appears to be a
      critical structure for drug-induced reward. Methylnaloxonium blocked place
      preference produced by ejaculation after infusion into the MPOA without affecting
      sexual behavior. Infusion of the antagonist into the NAC did not reduce the
      reinforcing properties of ejaculation. These data suggest that the MPOA may be a
      site where sexual reward is produced.

PMID- 8280391
TI  - Effects of a muscarinic antagonist on various components of female sexual
      behavior in the rat.
AB  - The effects of the muscarinic antagonist scopolamine on lordosis, solicitation,
      pacing, approach, attractivity, and activity were evaluated in ovariectomized
      rats brought into sexual receptivity with estrogen and progesterone. Systemic (1
      mg/rat) or intraventricular (10 micrograms bilaterally) administration of
      scopolamine significantly reduced the incidence of lordosis and solicitation
      behaviors and disrupted typical pacing of sexual contacts with a stimulus male.
      In addition, females avoided contact with a stimulus male, but not a stimulus
      female, following intraventricular infusion of scopolamine. The levels of general
      activity and frequencies of sexual contacts were similar in females treated
      intraventricularly with scopolamine and vehicle solutions. Consequently,
      scopolamine disrupted various components of sexual behavior, including lordosis,
      solicitation, pacing, and approach, without altering female attractivity or
      general activity.

PMID- 8280393
TI  - Functional lateralization for auditory temporal processing in male and female
      rats.
AB  - In 3 studies adult male rats showed significantly better discrimination of tone
      sequences with the right ear than with the left ear. This result parallels
      similar findings of left-hemisphere specialization for auditory temporal
      processing in humans and nonhuman primates. Furthermore, because clinical
      evidence supports a link between specialization of the left hemisphere for
      auditory temporal processing and for speech processing, these results may reflect
      evolutionary precursors to left-hemisphere language specialization. Because male
      rats showed a stronger ear advantage than female rats, the findings may relate to
      evidence of a stronger right ear advantage in men than in women. Finally, results
      suggest that neonatal handling enhances lateralization for auditory temporal
      processing in both sexes. Combined results implicate neuroendocrine mechanisms as
      important factors in the development of lateralization for auditory temporal
      processing.

PMID- 8280392
TI  - Neurons in the lateral subdivision of the habenular complex mediate the hormonal
      onset of maternal behavior in rats.
AB  - Expanding on research showing that radio-frequency-induced lesions of the
      habenular complex disrupt the hormonal onset of maternal behavior in rats, we
      explored the importance of neurons in the lateral (Lhb) subdivision of the
      habenular complex for the onset of maternal behavior. On Day 12 of pregnancy,
      bilateral cytotoxic lesions were produced in the Lhb with kainic acid or, as a
      control, just dorsal in the medial hippocampus. A 3rd group had radio-frequency
      induced Lhb and medial (Mhb) lesions. On Day 16 of pregnancy, Ss were
      hysterectomized-ovariectomized, given estradiol, and tested 48 hr later for 10
      days. Neuroanatomical tracing with fluoro-gold was then used to directly quantify
      the extent and location of Lhb neuron loss and to verify that Mhb neurons were
      intact. Cytotoxic lesions of the entire Lhb prevented the onset of all components
      of maternal behavior compared with controls. Results show that neurons in the
      Lhb, not the Mhb, are important for onset of maternal behavior in rats.

PMID- 8280394
TI  - Ultrasonic vocalizations are elicited from rat pups in the home cage by
      pentylenetetrazol and U50,488, but not naltrexone.
AB  - Although isolated rat pups emit ultrasonic vocalizations (USVs), those kept warm
      and undisturbed in the home cage with their littermates seldom do. Drugs were
      administered to 10-day-old pups in the home cage to determine whether
      pharmacological agents can elicit USV in this familiar environment. Ten-day-old
      Wistar rats were injected with U50,488, a highly selective kappa opioid agonist;
      pentylenetetrazol (PTZ), an anxiogenic drug that binds at the GABA-benzodiazepine
      receptor complex; or naltrexone (NLX), an opiate receptor blocker, and then were
      returned to their littermates in the home cage. U50,488 increased USV and
      activity levels, lowered body temperature, and disrupted contact with
      littermates. PTZ raised activity levels but had a smaller effect on vocalization
      rates and did not alter temperature or contact with littermates. Behavioral
      measures and body temperature were unchanged by NLX.

PMID- 8280395
TI  - Corticosteroid induction of threat-induced behavioral inhibition in preweanling
      rats.
AB  - Termination of ongoing behavior and assumption of defensive postures when
      threatened are adaptive characteristics of vertebrates. Altricial rat pups
      develop these characteristics by 14 days of age. At this time, pups inhibit their
      ultrasonic vocalizations and freeze when threatened. This emergence of behavioral
      inhibition is impaired when rats are adrenalectomized (ADX) at 10 days of age.
      That is, 14-day-old ADX pups exhibit deficits in freezing and continue to emit
      ultrasounds when confronted by an adult male rat. Studies also showed that
      removal of adrenal hormones does not potentiate vocalizations or render pups
      incapable of reducing their ultrasounds. More important, 3.0 mg/kg of
      corticosterone (CORT), but not lower doses, administered daily to ADX pups
      restored freezing, with lesser effects on ultrasound inhibition. Disrupting the
      developmental action of endogenous CORT appears to impair the ontogenetic
      expression of behavioral inhibition.

PMID- 8280396
TI  - Cocaine alters behavior in the rat fetus.
AB  - Changes in motor behavior and sensory responsiveness were characterized in rat
      fetuses on gestational Day 21 after acute administration of various doses of
      cocaine. An increase in fetal motor activity was evident in the 3 highest doses
      (5, 10, and 20 mg/kg). Cocaine-exposed Ss showed reduced facial wiping in
      behavioral bioassays of cutaneous sensitivity (10 and 20 mg/kg) and chemosensory
      responsiveness (20 mg/kg). Changes in other behavioral measures indicated that
      fetuses detected and responded to these stimuli, suggesting that reduced facial
      wiping was due to a disruption of sensorimotor integration or motor coordination.
      Study of the fetus in vivo can provide insights into the mechanisms of cocaine's
      deleterious effects on central nervous system and behavioral development.

PMID- 8280397
TI  - Daily caloric intake in intact and chronic decerebrate rats.
AB  - Daily caloric intake regulation was studied in chronic supracollicular
      decerebrate rats with a complete transection of the neural axis at the meso
      diencephalic juncture and in intact controls. For 1 week, each rat received 3
      intraorally delivered meals per day. They were challenged to maintain their 3
      meal daily intake over 1 week in which only 2 meals per day were delivered.
      Intact rats increased meal size to compensate for the lost opportunity to feed,
      whereas chronic decerebrate rats did not. Results suggest that, although the
      caudal brainstem, as previously shown (Grill & Kaplan, 1990), is sufficient to
      modulate ingestive behavior in taste reactivity and single-meal tests, it is not
      sufficient to regulate daily caloric intake. Although it is possible that chronic
      decerebrate rats retain a long-term regulatory competence that is somehow masked
      under the meal omission paradigm, forebrain-hindbrain interactions appear
      necessary for the coordination of short- and long-term intake control processes.

PMID- 8280398
TI  - Lidocaine infusion in a critical region of cerebellum completely prevents
      learning of the conditioned eyeblink response.
AB  - New Zealand white rabbits were implanted with cannulas in the dorsal or ventral
      aspect of the anterior interpositus nucleus. Three days (and 6 days for some
      dorsal-infusion animals) of standard tone-airpuff training was given with
      continuous infusion (constant rate of 0.2 microL/min) of lidocaine or saline. All
      animals were then given 3 days of training with no infusion. All lidocaine
      infused animals exhibited no conditioned responses in the 3 or 6 days of infusion
      training. Dorsal-infusion animals learned in the subsequent 3 days of no infusion
      training as if naive, that is, they exhibited no savings. Animals with ventral
      cannula locations learned during infusion training, as shown in postinfusion
      training. These results strongly support the hypothesis that the essential memory
      trace for eyeblink conditioning is formed and stored in the cerebellum.

PMID- 8280399
TI  - Contextual conditioning and auditory cue conditioning dissociate during
      development.
AB  - Following a single shock presentation, fear conditioning to an auditory cue and
      to the experimental context was assessed by measuring the rat's tendency to
      freeze. On the conditioning day 18-day-old rats showed as much freezing to the
      auditory cue as older rats. However, 18-day-old pups displayed much less freezing
      to the training context than pups 21- to 27-days old. The developmental
      dissociation between contextual and auditory cue conditioning parallels the
      dissociation produced by damage to the adult rat's hippocampal system (Kim &
      Fanselow, 1992; Phillips & LeDoux, 1992). The dissociation is also consistent
      with the developmental hypothesis that the configural association system develops
      late in comparison with the elemental association system (Rudy, 1991, 1992). The
      implications of the findings for the maturation of the neural components of the
      fear-conditioning circuit also are discussed.

PMID- 8280400
TI  - Prophylactic insulin. Is it 'safe'?

PMID- 8280401
TI  - Methotrexate in juvenile rheumatoid arthritis. Do the benefits outweigh the
      risks?
AB  - Juvenile rheumatoid arthritis (JRA) is a heterogeneous group of autoimmune
      diseases resulting in chronic idiopathic peripheral arthritis. The aetiology of
      JRA is unclear, and current pharmacotherapy is ameliorative rather than curative.
      Nonsteroidal anti-inflammatory drugs are given initially, but only one-third to
      one-fourth of patients are managed adequately with these agents. Advanced
      therapeutic drugs, frequently referred to as disease-modifying antirheumatic
      drugs or second-line agents, are given to the child with aggressive or resistant
      disease. Among these, the antimetabolite methotrexate has proven to be the most
      effective in alleviating articular disease manifestations and reducing laboratory
      parameters of inflammation. When given orally in low dosages (10 to 15
      mg/m2/week), methotrexate is well tolerated, without evidence of substantial bone
      marrow suppression or severe hepatotoxicity. Extensive long term tolerability
      data are not yet available for children, but longitudinal studies in adult
      patients with rheumatoid arthritis suggest that the drug may be given safely for
      extended periods in many patients. Paediatric rheumatologists are beginning to
      give higher dosages of methotrexate (up to 1 mg/kg/week) parenterally with some
      success. The long term consequences of higher dose methotrexate in children are
      unknown. Methotrexate has now become, and will probably remain for some time, the
      drug of first choice for children with recalcitrant JRA.

PMID- 8280402
TI  - A review of the adverse events profile of cefpirome.
AB  - Cefpirome is a new fourth generation injectable cephalosporin antibiotic. Its
      tolerability profile was established in a programme of 16 clinical studies
      involving 3103 patients in Europe and the US. The overall incidence of clinical
      adverse events with cefpirome was 21.9% compared with 27.1% with comparators
      (ceftazidime, imipenem, ceftriaxone). Adverse events thought possibly related to
      treatment occurred in 12.5% of patients receiving cefpirome and 13.7% of
      recipients of comparator agents. Withdrawals from treatment due to adverse events
      occurred in 5.1 and 5.0% of patients receiving cefpirome and comparators,
      respectively. The commonest adverse events thought possibly related to treatment
      were gastrointestinal symptoms (mainly diarrhoea in 1.6 and 1.7%, respectively)
      and rash (1.4 and 1.4%, respectively). Comparison with data obtained from the
      literature for ceftazidime, ceftriaxone and the third generation cephalosporins
      in general shows that the adverse event profile of cefpirome is similar to that
      of other broad-spectrum injectable cephalosporins.

PMID- 8280403
TI  - Adverse effects of macrolide antibacterials.
AB  - The renewed interest in macrolide antibacterials with expanded indications for
      clinical use, as well as their markedly increased usage, justifies the continuous
      search for new compounds designed to offer the patient not only enhanced
      bioavailability but also a reduced incidence of adverse effects. Macrolides are
      an old and well established class of antimicrobial agents that account for 10 to
      15% of the worldwide oral antibiotic market. Macrolides are considered to be one
      of the safest anti-infective groups in clinical use, with severe adverse
      reactions being rare. Newer products with improved features have recently been
      discovered and developed, maintaining or significantly expanding the role of
      macrolides in the management of infection. This review deals with the
      tolerability of the clinically available macrolide antibacterials. With the
      exception of drug interactions, adverse effects have been analysed during the
      last 40 years in many thousands of adult and paediatric patients. Recently
      developed derivatives have been compared with the older compounds, and the
      expected and well assessed adverse effects have been set apart from those which
      are unusual, very rare or questionable. Gastrointestinal reactions represent the
      most frequent disturbance, occurring in 15 to 20% of patients on erythromycins
      and in 5% or fewer patients treated with some recently developed macrolide
      derivatives that seldom or never induce endogenous release of motilin, such as
      roxithromycin, clarithromycin, dirithromycin, azithromycin and rikamycin
      (rokitamycin). Except for troleandomycin and some erythromycins administered at
      high dose and for long periods of time, the hepatotoxic potential of macrolides,
      which rarely or never form nitrosoalkanes, is low for josamycin, midecamycin,
      miocamycin, flurithromycin, clarithromycin and roxithromycin; it is negligible or
      absent for spiramycin, rikamycin, dirithromycin and azithromycin. Transient
      deafness and allergic reactions to macrolide antibacterials are highly unusual
      and have definitely been shown to be more common following treatment with the
      erythromycins than with the recently developed 14-, 15- and 16-membered
      macrolides. There have been case reports in the literature of 51 patients during
      the last 30 years who experienced uncommon or dubious adverse effects after
      treatment with older compounds and in which there appears to be strong evidence
      of a causal relationship with the drug. Only 3 cases had an unfavourable outcome,
      and these were patients administered erythromycin lactobionate intravenously too
      rapidly or at high dose. Targets of these occasional reactions are generally the
      heart, liver and central nervous system. Other unusual organ pathologies are
      related to immunomediated disorders more than to primary parenchymal toxicity, or
      to the rarely serious consequences of macrolide-induced alterations in intestinal
      microflora.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID- 8280404
TI  - A risk-benefit appraisal of transdermal estradiol therapy.
AB  - Estrogen replacement therapy (ERT) is very effective in relieving many menopausal
      symptoms such as hot flushes, night sweats, urogenital atrophy and psychological
      disturbances. Moreover, it is effective in the prevention of postmenopausal
      osteoporosis and has a favourable effect on some risk factors for cardiovascular
      disease in the long term, via several mechanisms including mediating effects on
      the lipid profile. Most of these beneficial effects are maintained with
      transdermal estradiol therapy, involving the use of a cutaneous delivery system
      attached to the skin which delivers a controlled rate of estradiol over a period
      of up to 4 days. However, the clear demonstration of a favourable effect on some
      risk factors for cardiovascular disease remains to be established. Transdermal
      administration of estradiol appears to be at least as effective as oral
      conjugated estrogen therapy on most of the end-points which have been evaluated,
      but allows a lower dose to be used, avoiding some of the metabolic adverse
      effects experienced with oral treatment. Endocrinological adverse effects, such
      as breast tenderness, breakthrough bleeding and fluid retention, are similar in
      both treatments, and can be minimised by dose adjustments in most cases. The most
      common adverse effects related to transdermal therapy are local skin reactions at
      the site of application. These are usually mild and transient in nature, and can
      be overcome by changing the site of application. Serious risks of transdermal
      therapy appear to be the same as those for other forms of ERT, namely an
      increased risk of endometrial hyperplasia and cancer with estrogen therapy alone.
      However, combination therapy involving the sequential administration of a
      progestogen has been shown to substantially reduce the risk of endometrial
      proliferation. The potential increased risk of breast cancer has been
      controversial and appears to be minimal with ERT. The role of progestogens on
      breast cancer risk remains controversial, but the data to date do not indicate
      any significant change in risk when progestogens are added to ERT.

PMID- 8280406
TI  - HIV pathogenesis and long-term survival.

PMID- 8280405
TI  - A risk-benefit appraisal of injectable NSAIDs in the management of postoperative
      pain.
AB  - The inadequacy of pain treatment has been demonstrated in many patient groups
      suffering from acute pain. The injectable nonsteroidal anti-inflammatory drugs
      (NSAIDs), including indomethacin, diclofenac, ketoprofen and ketorolac, provide
      relief from the pain associated with several different conditions. When
      administered alone or in combination with low doses of opioids, NSAIDs provide
      good pain relief after musculoskeletal trauma or operation. The main advantage of
      these agents is that they may form the first-line therapy for pain relief and
      thus decrease the need of opioids. This avoids respiratory depression which can
      be associated with opioids. In contrast to opioids, NSAIDs do not cause
      respiratory depression or have marked adverse effects on the central nervous
      system. However, they may be associated with adverse effects of the
      gastrointestinal tract, liver and kidneys, and may increase pre- and
      postoperative bleeding and cause allergic reactions. These effects are related to
      the ability of NSAIDs to inhibit prostaglandin synthesis. Use of NSAIDs has to be
      considered carefully in patients with asthma, allergy to aspirin and NSAIDs,
      atopy, peptic ulcer or bleeding disorders (such as abnormalities in blood
      coagulation or coagulation deficits). These considerations are especially
      important in elderly patients. Having taken these contraindications into account,
      many clinical studies have demonstrated that NSAIDs are at least as safe as
      opioids when administered in the short term. However, few studies have
      specifically monitored adverse effects or included patients over 65 to 70 years
      of age. In addition, patients with risk factors have often been excluded from the
      trials. Therefore, the risk-benefit ratio of NSAIDs requires further assessment.

PMID- 8280407
TI  - Cellular immune factors associated with mother-to-infant transmission of HIV.
AB  - OBJECTIVE: To study a possible correlate of protection in mother-to-infant
      transmission of HIV infection. In particular, to determine whether lack of HIV
      specific T-helper (TH) function as indicated by HIV and non-HIV antigen
      stimulated interleukin (IL)-2 production of mother and/or newborn peripheral
      blood leukocytes (PBL) is associated with mother-to-infant transmission of HIV.
      METHODS: PBL from 21 HIV-seropositive pregnant women and 23 cord blood leukocytes
      (CBL) from their offspring were studied for in vitro TH function by IL-2
      production in response to HIV and non-HIV antigens. Polymerase chain reaction
      (PCR) and viral culture assays were performed to determine HIV infection of the
      infants. RESULTS: PBL from 10 out of 21 (48%) mothers and from  eight out of 23
      (35%) CBL samples responded to two or more out of five synthetic gp 160 envelope
      (env) peptides. Three of the 23 (13%) offspring were shown to be HIV-infected by
      PCR and/or viral culture on follow-up. All three infected infants were from a
      subset whose CBL did not exhibit env-specific TH immunity. CONCLUSION: Our
      results demonstrate that fetal T cells can be primed to HIV env determinants in
      utero, suggest that HIV-specific TH immunity may be protective in newborns, and
      provide a possible means for identifying newborns who are at risk for HIV
      infection.

PMID- 8280408
TI  - Intestinal malabsorption of HIV-infected children: relationship to diarrhoea,
      failure to thrive, enteric micro-organisms and immune impairment. The Italian
      Paediatric Intestinal/HIV Study Group.
AB  - OBJECTIVE: To determine the features and the prevalence of intestinal-dysfunction
      in HIV-infected children and to investigate its relationship to diarrhoea, growth
      failure, immune dysfunction and enteric pathogens. DESIGN: Case controlled, cross
      sectional multicentre study. SETTING: Children enrolled in tertiary care Italian
      centres for paediatric HIV infection from June 1990 to June 1992. Intestinal
      function tests and investigation for enteric viruses were performed in Naples.
      PATIENTS: Forty-seven children with symptomatic HIV infection, six of whom had
      diarrhoea. Fifty non-infected children with diarrhoea and 48 healthy children
      were enrolled as controls for enteric viruses positivity and intestinal tests.
      METHODS: Intestinal function was investigated by measuring fat, protein and
      carbohydrate adsorption using the steatocrit method, and determining the faecal
      concentration alpha-1-antitrypsin and the d-xylose absorption, respectively.
      Microbiological studies included investigation for classical and opportunistic
      pathogens and for enteric viruses by electron microscopy in the stools of HIV
      infected children. The presence of viruses in the stools of HIV-negative children
      was also investigated. RESULTS: A high prevalence of intestinal-dysfunction was
      detected in HIV-infected children; faecal fat loss was detected in 14 out of 47
      (30%), carbohydrate malabsorption in 15 out of 47 (32%) and protein loss in eight
      out of 47 (17%) HIV-infected children. Mean values of xylose blood level and of
      steatocrit were significantly different from those of healthy controls. Four
      children with diarrhoea were positive for Cryptosporidium. The prevalence of
      enteric viruses was significantly increased in HIV-infected children (57%)
      compared with healthy controls (17%). Intestinal-dysfunction was not associated
      with diarrhoea, poor growth, enteric agents or degree of immune dysfunction.
      CONCLUSIONS: Intestinal-dysfunction, consisting of fat, carbohydrate and protein
      malabsorption, is a common feature of paediatric HIV infection. Although not
      clinically evident, it may contribute to further worsening of the disease.

PMID- 8280409
TI  - Risk factors for Clostridium difficile-associated diarrhoea in HIV-infected
      patients.
AB  - OBJECTIVE: To identify risk factors associated with a first episode of
      Clostridium difficile-associated diarrhoea (CDAD) in patients with HIV infection.
      DESIGN: A case-control study. SETTING: University teaching hospital HIV inpatient
      unit. PATIENTS AND METHODS: Nineteen HIV-infected patients with CDAD, defined as
      diarrhoea with positive stool culture for Clostridium difficile (CD) and positive
      stool cytotoxin B assay, were compared with 38 randomly selected controls (HIV
      infected patients hospitalized on the ward on the day the matched case was
      diagnosed). CD isolates were phenotyped by electrophoretic protein patterns.
      RESULTS: The incidence of CDAD among HIV-infected patients was 4.1/100 of patient
      admissions. On univariate analysis, cases were more likely to have used
      clindamycin [11 out of 19 compared with four out of 38; odds ratio (OR) 19; 95%
      confidence interval (CI), 2-160; P = 0.0007], and pyrimethamine (14 out of 19
      compared with 13 out of 38; OR, 4.8; 95% CI, 1.4-16, P = 0.02) in the month
      before diagnosis, and to have had cerebral toxoplasmosis (12 out of 19 compared
      with 13 out of 38; OR, 2.8; 95% CI, 0.9-8.6; P = 0.09). There was also a
      significant increase of the risk of CDAD as duration of hospitalization in the
      ward increased (chi 2 for trend, P = 0.007). Multivariate models associated two
      risk factors with CDAD: clindamycin use (OR, 42; 95% CI, 2-813; P = 0.01), and
      prolonged hospitalization in the ward (OR, 3.6 per week in the ward; 95% CI, 1
      13, P = 0.048). Of 18 available CD isolates, 15 (83%) had identical
      electrophoretic protein pattern. CONCLUSIONS: Clindamycin use and prolonged
      hospitalization in the ward were the main risk factors associated with CDAD in
      this study. These observations, together with the occurrence of one major
      phenotype of CD, suggest nosocomial transmission of CD in the ward.

PMID- 8280410
TI  - Successful treatment of AIDS-related cryptosporidial sclerosing cholangitis.
AB  - OBJECTIVE: Cryptosporidium is a well recognized cause of AIDS-related sclerosing
      cholangitis for which no efficacious therapy exists at present. We evaluated the
      efficiency of the combination of paromomycin and letrazuril in the treatment of
      this condition. CASE REPORT: We report a case of cryptosporidial cholangitis in a
      patient with AIDS who responded to treatment with intravenous paromomycin
      followed by oral letrazuril as maintenance therapy. CONCLUSION: The combination
      of paromomycin and letrazuril should be considered in the treatment of AIDS
      related sclerosing cholangitis.

PMID- 8280411
TI  - A nosocomial outbreak of multidrug-resistant Mycobacterium bovis among HIV
      infected patients. A case-control study.
AB  - OBJECTIVE: To identify risk factors in a nosocomial outbreak of multidrug
      resistant Mycobacterium bovis (MDRMB) tuberculosis (TB) among HIV-infected
      patients. DESIGN: We evaluated the study period (from the first to the last MDRMB
      smear-positive patients hospitalized in the unit) using a case-control study with
      three control groups. Since MDRMB is extremely rare, we assumed that a single
      strain was responsible for all six cases. SETTING: A 19-bed infectious diseases
      unit in Paris, France. PATIENTS: The index case was an AIDS patient who was
      hospitalized in September 1989 because of MDRMB TB. The cases were five HIV
      infected patients who developed MDRMB TB between January 1990 and October 1991.
      Controls were randomly selected from HIV-infected patients in our unit during the
      study period (case-control study 1, 15 patients), during the contact period (at
      least one MDRMB smear-positive patient hospitalized in the unit; case-control
      study 2,20 patients), and patients matched according to the length of contact
      (case-control study 3, 24 patients). INTERVENTIONS: After detecting the
      nosocomial outbreak, we took respiratory isolation precautions for all patients
      suspected of having active TB. MAIN OUTCOME MEASURES: Risk factors for MDRMB
      nosocomial transmission, and the occurrence of new cases of MDRMB infection in
      HIV-infected patients and health-care workers after the introduction of isolation
      precautions. RESULTS: The most important predictor of nosocomial transmission of
      MDRMB to HIV-infected patients was the (mean +/- s.d.) length of contact in days
      [cases, 22 +/- 15.8; study 1 controls, 11.2 +/- 18.9 (P = 0.07); study 2
      controls, 14.6 +/- 8.5 (P = 0.043)]. Only one case of MDRMB TB resulted from
      exposure to MDRMB-smear-positive patient after the introduction of respiratory
      isolation measures. The incubation period in the single health-care worker who
      developed MDRMB TB was longer than in the cases. CONCLUSION: In a nosocomial
      outbreak of MDRMB TB, the contact time was the main risk factor of transmission
      to HIV-infected patients. Respiratory isolation measures appear to be effective.

PMID- 8280412
TI  - General and HIV-1-associated morbidity in a rural Ugandan community.
AB  - OBJECTIVES: The AIDS epidemic in sub-Saharan Africa affects whole communities,
      adding to the already high burden of morbidity. Reports of AIDS cases are usually
      from hospital attenders, often diagnosed using the World Health Organization
      (WHO) clinical case definition. Little is known about the extent of HIV
      associated morbidity in the general population. The objectives of this study were
      to describe the prevalence of (1) markers of general morbidity and (2) the
      criteria of the WHO clinical case definition for AIDS and (3) to determine the
      association between these markers and HIV-1 serostatus in a rural Ugandan
      community. METHODS: A survey was conducted among the adult population (aged > or
      = 13 years) of 15 neighbouring villages in Masaka District, south-west Uganda.
      The survey included medical history, physical examination and testing for HIV-1
      antibodies. RESULTS: The HIV-1 seroprevalence among 4175 out of 5278 (79%)
      eligible adults was 8.2%. Current health problems were reported by 57.6% of
      adults, with increased rates in HIV-1-positive subjects, women and older people.
      Five of the 10 most common complaints showed significant associations with HIV-1
      status, as did reported genital ulcer and vaginal discharge. The crude HIV-1
      attributable disease burden in the population was 1.2% for current illness, 4.3%
      for previous serious illness and 9.9% for illness leading to hospital admission.
      Overall, 11 (3.3%) of the HIV-1-positive and nine (0.2%) of the HIV-1-negative
      subjects had AIDS as defined by the clinical case definition. The positive and
      negative predictive values and specificity were 55.0, 92.0%, and 99.8%,
      respectively. CONCLUSIONS: Against a background of high general morbidity, we
      observed a relatively small population attribution of HIV-1-associated morbidity.
      The results indicate that the clinical AIDS case definition may provide a useful
      tool for population surveys.

PMID- 8280413
TI  - Infection and morbidity in patients with tuberculosis in Nairobi, Kenya.
AB  - OBJECTIVE: To examine the role of acute infection as a cause of morbidity in
      patients with tuberculosis. DESIGN: Cross-sectional documentation of predefined
      acute morbid events. SETTING: Infectious Diseases Hospital, Nairobi, Kenya.
      PATIENTS: Adults (> or = 15 years), inpatients and outpatients with a diagnosis
      of tuberculosis presenting with one or more of a series of clinical features. A
      new event was defined as one occurring at least 1 week after the initial event.
      INTERVENTIONS: Patients' treatment was modified depending on the results of
      laboratory investigations. MAIN OUTCOME MEASURES: There were 642 events from 398
      patients, 235 HIV-positive patients had 438 events and 163 HIV-negative patients
      had 204 events (P < 0.0001). Forty-two out of the 235 (18%) HIV-positive patients
      were bacteraemic compared with nine out of the 163 (6%) HIV-negative patients (P
      = 0.0003). The most common isolates from blood were Salmonella typhimurium and
      Streptococcus pneumoniae. RESULTS: Faecal specimens were obtained more commonly
      from HIV-positive patients (P < 0.001), and often contained bacterial pathogens.
      CONCLUSIONS: Many of the causes of morbidity in patients with tuberculosis and
      HIV are not due to tuberculosis or antituberculous therapy, and will not be
      identified without microbiological investigation.

PMID- 8280414
TI  - Beta 2-microglobulin, HIV-1 p24 antibody and acid-dissociated HIV-1 p24 antigen
      levels: predictive markers for vertical transmission of HIV-1 in pregnant Ugandan
      women.
AB  - OBJECTIVES: To evaluate the clinical utility of plasma beta 2-microglobulin (beta
      2M) levels, acid-dissociated HIV-1 p24 antigen, and HIV-1 p24-antibody titers in
      predicting HIV-1 vertical transmission in 227 HIV-1-infected Ugandan pregnant
      women. DESIGN: Plasma beta 2M levels, acid-dissociated HIV-1 p24-antigen
      positivity, and HIV-1 p24-antibody titers were determined using commercial enzyme
      immunoassays (EIA) in a Ugandan cohort of 52 HIV-1-seropositive transmitting
      mothers, 175 HIV-1-seropositive non-transmitting mothers, and 52 seronegative
      mothers within 6 weeks prior to delivery. RESULTS: Transmitter mothers had
      significantly higher plasma concentrations of beta 2M (1.80 +/- 1.13 mg/l) than
      non-transmitter seropositive mothers (1.32 +/- 0.81 mg/l; P = 0.0013). Similarly,
      a significantly higher proportion of transmitter mothers had detectable p24
      antigen than non-transmitter mothers [six out of 51 (11.8%) versus six out of 173
      (3.5%); P = 0.03]. Compared with the vertical transmission rate of 23% in the
      seropositive group, the positive predictive values of a beta 2M level > 1.5 mg/l
      or detectable HIV-1 p24 antigen for vertical transmission were 34 and 50%,
      respectively. Five of six (83.3%) seropositive mothers with both a beta 2M level
      > 1.5 mg/l and detectable p24 antigenemia transmitted HIV-1 infection to their
      infants compared with 25 of 124 (20.2%) seropositive mothers with values below
      the cut-off values for both tests (P = 0.00249). However, beta 2M was not found
      to be a significant independent predictor of vertical transmission when analyzed
      in a multivariate model with p24 antigenemia. There was no significant difference
      in HIV-1 p24-antibody titers in transmitter mothers versus non-transmitter
      mothers (P = 0.299). CONCLUSION: beta 2M levels and acid-dissociated HIV-1 p24
      antigen assays may be used to predict which HIV-1-infected pregnant women are at
      greatest risk for vertical transmission. However, only the p24-antigen test was
      independently predictive of vertical transmission and its clinical utility is
      limited.

PMID- 8280415
TI  - Geographic and temporal stability of HIV seroprevalence among pregnant women in
      Bujumbura, Burundi.
AB  - OBJECTIVE: To establish whether HIV seroprevalence in Bujumbura is stable or
      continuing to increase. METHODS: HIV seroprevalence data among pregnant women
      from 1986 were compared with comparable data from 1991-1992. RESULTS: HIV
      seroprevalence among antenatal clinic attendees at three sites was 10.5, 28.0 and
      11.9% in 1986, compared with 7.7, 25.6 and 12.4%, respectively, in 1991-1992. A
      weighted least squares analysis showed significant differences in HIV
      seroprevalence between the different sites (chi 2, 71.71; P > 0.0001), but no
      evidence of any differences between the 1986 and the 1991-1992 prevalence levels
      (chi 2, 0.51; P = 0.6). CONCLUSIONS: Bujumbura appears to be in the endemic phase
      of the spread of HIV. The stable geographic variation among clinic populations in
      Bujumbura suggests the need for focused interventions, and a general need for
      surveillance data to be gathered from numerous sites so to identify those with
      the highest incidence of HIV infection.

PMID- 8280416
TI  - Factors associated with HIV seropositivity in European injecting drug users. The
      European Community Study Group on HIV in Injecting Drug Users.
AB  - OBJECTIVE: To study factors associated with HIV seropositivity among European
      injecting drug users (IDU). METHODS: Data on behavioural and other factors
      potentially associated with HIV status were collected retrospectively by personal
      interview with IDU (n = 2330) in a multicentre cross-sectional survey conducted
      in 12 European countries from 1989 to 1990. HIV status tested at the time of the
      survey was examined in relation to demographic data, history of imprisonment,
      travel to foreign countries, high-risk drug-using practices in the previous 6
      months (re-using other IDU's injecting equipment without effective disinfection)
      and high-risk sexual behaviour in the last 6 months (multiple partners, unless
      none was IDU and condoms were always used). Analysis excluded IDU who claimed to
      be seropositive from previous testing. RESULTS: Imprisonment was significantly
      associated with current HIV status [odds ratio (OR), 1.70; 95% confidence
      interval (CI), 1.2-2.87]. High-risk drug-use practices were significantly
      associated with current HIV status in respondents not previously tested (OR,
      2.86; 95% CI, 1.09-7.35) but not in respondents claiming to be seronegative. No
      significant association was found for high-risk sexual behaviour. CONCLUSIONS:
      Our experience supports the validity of retrospective investigation of behaviour
      in a population that is notoriously difficult to study. However, any
      interpretation of the apparently different associations of HIV status with high
      risk sexual behaviour and high-risk drug-use practices must consider that factors
      tending to attenuate the correlations may operate differently in these two areas.

PMID- 8280417
TI  - Psychological distress, drug and alcohol use as correlates of condom use in HIV
      serodiscordant heterosexual couples.
AB  - OBJECTIVE: To investigate the relationship between psychological distress,
      alcohol, drug and condom use in HIV-serodiscordant heterosexual couples. METHODS:
      Structured interviews were conducted to collect demographic information, detailed
      data on psychological distress, drug and alcohol use and sexual behavior.
      RESULTS: Analyses were based on 106 pairs of sexually active discordant couples.
      Significant differences among heterosexual condom users and non-users varied
      according to gender and HIV serostatus. Affect domains of interpersonal
      sensitivity and hostility were significant, as were the variables of regular drug
      or alcohol use and combining sex with drugs or alcohol. Employment was strongly
      associated with condom use in HIV-negative women whose regular sexual partners
      were HIV-positive men. CONCLUSION: The risk of vaginal sex without condoms in HIV
      serodiscordant heterosexual couples may be reduced by specific psychological
      counseling and attention to drug and alcohol use as risk factors. Further
      research on the effect of employment of HIV-negative women is required.

PMID- 8280418
TI  - HIV infection in injecting drug users attending centres in England and Wales,
      1990-1991.
AB  - OBJECTIVE: To monitor trends in HIV infection and associated risk behaviours in
      injecting drug users (IDU) in England and Wales. DESIGN: Ongoing voluntary
      unlinked anonymous cross-sectional survey. METHOD: IDU attending centres in 1990
      and 1991 were invited to complete a brief questionnaire requesting demographic
      and behavioural information, and to provide a saliva sample to be tested for
      antibodies to HIV and to the core antigen of hepatitis B virus (HBV). RESULTS: In
      1990, 1.2% (19 out of 1543) of samples from 33 centres, and in 1991 1.8% (25 out
      of 1417) of samples from 37 centres contained antibody to HIV. Antibody t9 HBV
      core-antigen was found in 33 and 31% of IDU in 1990 and 1991, respectively. The
      prevalence of HIV infection in IDU attending centres in London (4.2%) was higher
      than in those attending centres elsewhere (0.8%). The prevalence of HIV infection
      in 1991 varied between individual centres from 0 to 10.6%, and at many centres
      outside London no IDU were infected with HIV. In the same year the prevalence of
      past infection with HBV varied from 14 to 54%, and IDU who had evidence of HBV
      infection were found among attenders in nearly all centres. The prevalences of
      sharing injecting equipment and risky sexual behaviour were high at many centres.
      The prevalence of HIV infection was higher in IDU who had started to inject in
      1985 or earlier, than in those who started injecting later. In each year,
      approximately half the IDU surveyed reported having had a voluntary confidential
      HIV-antibody test, and the prevalence of HIV infection was five times higher in
      those tested than in those who had not been tested. CONCLUSIONS: HIV prevalence
      in IDU attending centres in England and Wales was low in 1990-1991. There is some
      indication that IDU have modified their injecting or sexual behaviour, but even
      at existing reduced levels of risk behaviour, transmission can occur in HIV is
      introduced into previously unexposed groups.

PMID- 8280419
TI  - The New Zealand Partner Relations Survey: methodological results of a national
      telephone survey.
AB  - OBJECTIVE: To implement and evaluated a national survey of sexual behaviour using
      computer-assisted telephone interviewing (CATI). DESIGN: A two-stage stratified
      national sample survey in which households were selected by random digit-dialing
      (RDD), with a single eligible interviewee per selected household, followed by
      subsample surveys of non-contacts and refusals to determine eligibility. METHODS:
      A 15-minute questionnaire based on the Global Programme on AIDS (GPA)/World
      Health Organization (WHO) protocol was administered by telephone to a nationally
      representative sample of 2361 respondents in the 18-54-year age group. RESULTS:
      The overall response rate was 63%, but lower in the cities, in the 18-24 age
      group, and among men. Three-quarters of surveyed non-contacts, and a quarter of
      re-surveyed refusals, did not meet the eligibility criteria for the study. Less
      than 20% of refusals cited the subject matter of the survey as the reason for
      refusal. Item non-response (< 1%) increased with question sensitivity, and varied
      by respondent age, ethnicity and partnership status. Men reported twice as many
      adult lifetime partners as women. CONCLUSIONS: The GPA/WHO protocol can be
      successfully adapted to administration by telephone, with adequate response rates
      and exceptionally low levels of item non-response. CATI is a cost-effective
      method for collecting national information on sexual behaviour in countries where
      there is a high level of telephone ownership. Used in conjunction with RDD, it
      can overcome problems of sample design in settings where there is no
      comprehensive population-sampling frame. Checks on item sensitivity and partner
      estimates suggest that acceptable levels of reliability can also be achieved.

PMID- 8280420
TI  - AIDS in Colorado Springs: is there an epidemic?
AB  - OBJECTIVE: To analyze trends and patterns of HIV infection in a medium-sized
      community in the United States. METHODS: Surveillance for AIDS and HIV infection
      was conducted by private physicians, military and public clinics, and blood and
      plasma donation centers. HIV-positive individuals were contacted and asked to
      refer their sex and injection partners for HIV-antibody testing. Prostitutes,
      injecting drug users and their sex partners were studied. Selected physicians
      were surveyed to assess under-reporting. RESULTS: The 740 HIV-infected adults (67
      with documented seroconversion) included 506 with no evidence of AIDS, 58 living
      with AIDS, and 176 who had died. Of the 126 patients cared for by local
      physicians, 107 (85%) had been reported. No major changes in behavioral risk
      factors or increases in the number of HIV-infected individuals occurred between
      1986 (128) and 1992 (95). CONCLUSIONS: Characteristics of individuals at risk and
      incidence of HIV infection have remained stable from 1981 to 1992. Analysis of
      data from the comprehensive surveillance and control program established in
      Colorado Springs in response to the AIDS epidemic suggests that, unlike the
      nation's epicenters, HIV incidence in this location is neither widespread nor
      rapidly increasing. The age distribution of reported cases is slowly increasing,
      and the ratio of newly reported cases to deaths is declining, implying stable or
      decreasing incidence; deaths may soon exceed new cases. Using data routinely
      available to public health officials, we conclude that the epidemiologic picture
      of AIDS--like the clinical one--must be heterogeneous, and that rational planning
      for the impact of AIDS should be based on the collection and analysis of local
      data.

PMID- 8280421
TI  - Changing incidence of Pneumocystis carinii pneumonia as initial AIDS defining
      disease in the United Kingdom.
AB  - OBJECTIVE: To determine whether the incidence of Pneumocystis carinii pneumonia
      (PCP) as the initial AIDS-defining disease in adult AIDS cases in the United
      Kingdom is changing over time and to examine factors likely to affect it.
      SUBJECTS AND METHODS: A total of 4419 adult AIDS cases diagnosed in the United
      Kingdom between January 1989 and December 1992 were analysed using logistic
      regression models. An initial diagnosis of PCP was used as the outcome variable
      and the possible effects of age, sex, exposure category, ethnic group, half year
      of diagnosis, geographical area of report, and whether or not the individuals had
      been aware of their HIV infection when AIDS was diagnosed was examined. RESULTS:
      A significant decline in PCP incidence was observed over time. Incidence of PCP
      declined among subjects who had been aware of their infection for 9 months or
      more before AIDS diagnosis. There was no evidence of a change in PCP incidence
      over time for subjects who had had HIV infection diagnosed 3 or less months
      before an AIDS diagnosis. Individuals who had been aware of their HIV infection,
      individuals reported from the Thames health regions, and non-white patients were
      much less likely to have had a diagnosis of PCP. CONCLUSIONS: The decline of PCP
      incidence in subjects aware of their serostatus, and therefore more likely to
      have received primary prophylaxis, suggests that they may have benefited from
      this treatment. Our findings provide evidence of the value of an early HIV
      diagnosis and confirmation of the beneficial effects of primary prophylaxis for
      PCP.

PMID- 8280422
TI  - High viral burden in lymph nodes during early stages of HIV-1 infection.

PMID- 8280423
TI  - Time course of antigenaemia and seroconversion in infants with vertically
      acquired HIV-1 infection.

PMID- 8280424
TI  - Increase in double-positive CD4+CD8+ peripheral T-cell subsets in an HIV-infected
      patient.

PMID- 8280425
TI  - Detection of false antibodies to HIV-1 in urine.

PMID- 8280426
TI  - Patterns of multiple-drug hypersensitivities in HIV-infected patients.

PMID- 8280427
TI  - Mucosal colonization by pyogenic bacteria among children with HIV infection.

PMID- 8280428
TI  - The prevalence of antibodies to HIV-1 and HIV-2 in onchocerciasis-endemic rural
      areas in southern Benin.

PMID- 8280429
TI  - Antigenic evidence of the presence of the aberrant HIV-1ant70 virus in Cameroon
      and Gabon.

PMID- 8280430
TI  - Heterogeneity of HIV-1 in South Africa detected by polymerase chain reaction.

PMID- 8280431
TI  - Polymerase chain reaction in the diagnosis of Toxoplasma encephalitis.

PMID- 8280432
TI  - Structure of diaquatetrakis(mu-2,6-difluorobenzoato-kappa O:kappa
      O')dicopper(II).
AB  - The structure consists of centrosymmetric dimeric units, [Cu(C6H3F2COO)2(H2O)]2,
      formed from the bridging of pairs of copper(II) ions by carboxylate groups from
      four different 2,6-difluorobenzoate anions. The distorted octahedral coordination
      about each CuII ion consists of four carboxylate O atoms, a water molecule and a
      centrosymmetrically related copper ion. The Cu...Cu distance is 2.613 (1) A. The
      most significant feature of the crystalline structure is the water-mediated
      coordination of one of the carbon-bound F atoms to the copper ion through a
      strong C--F...H--O hydrogen bond [F...O 2.962 (4) A, F...H--O 163 degrees]. Each
      2,6-difluorobenzoate aryl group is twisted considerably from its corresponding
      carboxyl group plane [48.9, 104.2 degrees].

PMID- 8280433
TI  - Structure of diphenanthro[1,2-b;2',1'-d]-furan at 191 K.
AB  - Diphenanthro[1,2-b;2',1'-d]furan crystallizes in space group Pnma (No. 62) with
      the mirror plane bisecting the molecule and passing through the furan O atom.
      Although exhibiting packing similar to that of dibenzofuran, this
      diphenanthrofuran showed no disorder of the sort found in that close molecular
      analog. The C atoms of the individual phenanthrene rings of the title compound
      have a mean deviation of 0.027 (21) A from the best least-squares plane
      describing the rings. The configuration and conformation of the individual
      phenanthrene rings in this diphenanthrofuran closely match the theoretical and
      experimental results for phenanthrene itself. Overall, this diphenanthrofuran
      molecule adopts a distinct V shape, the dihedral angle between the least-squares
      best-fit planes of the phenanthrene rings being 11.0 (1.2) degrees.

PMID- 8280434
TI  - Redetermination of the structures of 1-naphthoic acid and 2-naphthoic acid.
AB  - The structures of 1-naphthoic acid and 2-naphthoic acid have been investigated in
      order to determine the degree of disorder of the carboxylic acid groups. 1
      Naphthoic acid was found to be completely ordered with C--O bond lengths of 1.214
      (3) and 1.312 (3) A, and C--C--O bond angles of 124.8 (2) and 114.2 (2) degrees.
      2-Naphthoic acid was found to possess a significant degree of disorder with C--O
      bond lengths of 1.256 (3) and 1.274 (3) A, and C--C--O bond angles of 117.7 (2)
      and 119.1 (2) degrees. In 2-naphthoic acid, the acid H atom was refined at two
      sites with 0.5 occupancy at each. Analysis of the anisotropic displacement
      ellipsoids of the acid O atoms for each structure demonstrated that these
      parameters are consistent with thermal motion of the O atoms. These results
      indicated that the proton, but not the O atoms, is disordered in the carboxylic
      acid group of 2-naphthoic acid. In each structure, the acid molecules form cyclic
      dimers about inversion centers, with an O...O(acceptor) distance of 2.653 (3) in
      1-naphthoic acid and 2.618 (3) A in 2-naphthoic acid. The cyclic dimers form
      layers in each of these structures wherein lateral closest intermolecular
      approaches to the acid O atoms are from ring H atoms. The intermolecular O...H
      close approaches, together with the intramolecular close approaches, are very
      uniform in distance and angle of approach for the two O atoms in the 2-naphthoic
      acid structure.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280435
TI  - Antibody-based immunoadsorption as a therapeutic means.
AB  - Polyclonal antibodies against human low-density lipoprotein (LDL), covalently
      coupled to Sepharose CL-4B, are used to remove LDL from the plasma of familial
      hypercholesterolemic patients. During a single treatment LDL-cholesterol is
      lowered by more than 60%, and plasma viscosity is decreased by 10%. The usual
      treatment frequency is once a week. The possible development of human antisheep
      antibodies was followed for up to 5 years. The ELISA signal rose slightly above
      baseline reaching a plateau within the first year. Clinically, there have been no
      signs of column-related adverse reactions. Due to the versatility of
      immunoapheresis it is also applicable to deplete IgG by coupling antihuman IgG
      antibodies. These columns might be indicated for patients with high panel
      reactivity to enable organ transplantation and for patients with autoimmune
      disease. In vitro tests with plasma from high-panel-reactive dialysis patients
      have shown that IgG could be depleted by 95% across all subclasses and that panel
      reactivity could be reduced from 91 to 25%.

PMID- 8280436
TI  - Adsorptive plasma treatment: optimization of extracorporeal devices and systems.
AB  - Devices in current use for adsorptive plasma treatment have, in many cases, been
      adapted from other types of separation processes. Minimizing system volume and
      quantity of ligand per mass transferred are proposed as appropriate design goals
      for an adsorptive plasma treatment system. The process consists of two
      operations: cell/plasma separation and solute adsorption/desorption. An example
      of an optimally designed membrane cell separator is presented which adds a
      negligibly small volume to the system. By overcoming mass transfer limitations,
      both volume and ligand quantity associated with the sorbent device can be
      minimized. Combining both of the above operations in a single device is also
      feasible. Examples are discussed of optimally designed sorbent devices and
      devices which combine cell separation/solute adsorption.

PMID- 8280437
TI  - Desperate appliances: a short review of therapies for fulminant hepatic failure.
AB  - In this work, we review the current status of accepted and experimental therapies
      for fulminant hepatic failure, we attempt to estimate chances of success and
      outline a protocol by which such therapies tested.

PMID- 8280438
TI  - Use of sorbent columns and haemofiltration in fulminant hepatic failure.
AB  - Artificial liver support systems were developed to remove potential toxins from
      the circulation of patients with liver failure. A wide range of substances have
      been implicated in the toxic manifestations of liver failure, but no substance(s)
      has been identified as being of key importance. Charcoal haemoperfusion appeared
      to be beneficial in early studies, but when clinical trials were performed in 137
      patients at King's College Hospital there was no significant improvement in
      survival over intensive care alone. There have been many studies using
      haemodialysis/filtration systems, where an improvement in conscious level of the
      patient was reported, but the effect on survival was less clear. Recently in
      Japan, continuous high volume haemofiltration with the addition of plasma
      exchange has been used to support liver failure patients. In liver failure,
      endotoxaemia and increased cytokine production are important in the pathogenesis
      of circulatory failure. Experiments on adsorbents to remove cytokines have shown
      that Amberlite XAD-7 resin can remove significant amounts of tumour necrosis
      factor and interleukin-6 from liver failure plasma. The development of hepatocyte
      bioreactors with synthetic and metabolic function for clinical use will be a
      major advance in liver support.

PMID- 8280439
TI  - Extracorporeal liver assist in the treatment of fulminant hepatic failure.
AB  - Our goal in developing a liver assist device is to provide liver support and
      improve the metabolic state of the patient so that the native liver has the
      opportunity to regenerate. Failing this, the patient should at least remain in
      satisfactory health so that liver transplantation can be performed safely. We
      have no idea how much metabolic support will be required to sustain life, but we
      have a set a goal of 20% of the normal hepatocyte mass. Our initial results
      suggest that this is an appropriate number, and a clinical trial to determine
      safety and efficacy is under way at the Texas Medical Center.

PMID- 8280440
TI  - [Nutritional supplements: science or business. Facts and myths].

PMID- 8280441
TI  - [Intermittent methylprednisolone pulse therapy for myasthenia gravis in
      childhood].
AB  - We studied the effects of the intermittent methylprednisolone pulse (IMP) therapy
      without the maintenance steroid therapy for 6 children with myasthenia gravis; 3
      cases with generalized type and 3 with ocular type. None of them was controlled
      satisfactorily by oral steroid therapy or anti-choline esterase agents. Two cases
      with generalized type and the other two with ocular type achieved remission by
      the initial pulse therapy, and were kept under good control by subsequent IMP
      therapy performed periodically or at the time of relapse. The other two cases
      could not be introduced to complete remission by the initial pulse therapy, but
      improved gradually by subsequent periodical IMP therapy. The IMP therapy without
      maintenance of oral steroid therapy is more useful as compared with oral
      administration of steroids, in controlling myasthenia gravis and also in
      preventing side effects due to steroid therapy.

PMID- 8280442
TI  - [A clinical study of severely mental and motor retarded children].
AB  - From 1986 to 1992, we examined 73 patients with severely mental and motor
      retardation. The onset age of 82% of the patients was less than one year. The
      number of patients was 29 and 54, in 1986 and 1992, respectively. The etiology
      for 48 patients was congenital or neonatal diseases. All patients were unable to
      eat by themselves. Tracheotomy was made on ten cases. Eight patients were on home
      oxygen therapy. Twenty-one patients had the history of mechanical ventilation.
      Sixty-three patients had the history of hospitalization and their total number of
      hospitalization was 343. About a half of hospitalizations was for respiratory
      disturbance. The number of cases with long term hospitalization recently
      increased. Ten patients died, only one patient died of pneumonia. Unexpected
      sudden death occurred in three patients.

PMID- 8280443
TI  - [Developmental changes in proton MR spectroscopy of the brain].
AB  - Volume-selective proton MR spectroscopy (1H-MRS) of the brain was performed on a
      1.5 T magnet in 31 healthy children aged from 1 month to 15 years and one healthy
      adult. Peaks of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were
      observed in all cases on 1H-MRS, but not lactate. On 1H-MRS of the right parietal
      region, with advancing age, 1H-MRS revealed an increase in the ratios of NAA to
      Cho and NAA to Cr and a decrease in Cho to Cr. The most rapid change was noted
      during the first one to three years of life. 1H-MRS of the right frontal region
      was also performed in eleven cases. The ratio of NAA/Cho was smaller in the right
      frontal region than in the right parietal region. From this result, it may be
      suggested that the neuronal maturation in the frontal region delays as compared
      with the parietal region.

PMID- 8280444
TI  - [MRI measurements of the brain stem and cerebellum in high functioning autistic
      children].
AB  - To determine involvements of the brain stem and/or cerebellum in autism, we
      compared midsagittal magnetic resonance images of the brains of high functioning
      autistic children with those of normal controls. We found that the midbrain and
      medulla oblongata were significantly smaller in these autistic children than in
      the control children. The pons area did not differ between the two groups, nor
      was there any difference in the cerebellar vermis area. The ratio of the brain
      stem and cerebellum to the posterior fossa area did not differ significantly
      between the high functioning autistic and the control children. The development
      of the cerebellar vermis area was delayed in autistic children as compared with
      that in the control children. Thus, it was suggested that significant anatomical
      changes in the midbrain and medulla oblongata existed in the autistic children.

PMID- 8280445
TI  - [Relationship between child epilepsy and MRI findings in von Recklinghausen
      neurofibromatosis (NF 1)].
AB  - Fourteen children meeting the NIH consensus diagnostic criteria for NF 1 were
      evaluated at the Department of Pediatrics, Himeji Red Cross Hospital. MRI and EEG
      were examined in all patients, respectively. Four of 14 patients had a history of
      epilepsy, two had suffered West syndrome, one had complex partial seizures and
      one had secondary generalized partial epilepsy. Seven (50%) of 14 patients showed
      abnormal MRI; three (75%) of 4 patients with epilepsy and four (40%) of 10
      patients with epilepsy showed low intensity on T1 weighted images and
      hyperintensity on T2 weighted images in the globus pallidus and brainstem. These
      results suggest that children with NF 1 have a spectrum of MRI abnormalities,
      irrespective of existence of epilepsy.

PMID- 8280447
TI  - [Congenital multiple anomaly syndrome with recurrent vomiting accompanied with
      latent SIADH; a case report].
AB  - A 13-year-old girl with multiple minor anomalies and severe mental retardation
      had recurrent episodes of severe vomiting. At each episode, marked elevations of
      plasma ADH, ACTH, cortisol and salivary type amylase were found with reduction of
      serum Na level and osmolarity. This case is similar to that with periodic ACTH
      ADH discharge syndrome (Sato). However, she had underlying disease, and neither
      hypertension nor depressive state was observed. Latent SIADH was detected by
      water loading test. After DZP administration, ADH secretion was suppressed in
      this test, and actually the duration of each attack was shortened. We considered
      that her vomiting was closely related with hypothalamic dysfunction, especially
      latent SIADH.

PMID- 8280446
TI  - [A female case of isolated angiitis of the central nervous system].
AB  - Isolated angiitis of the central nervous system (IACNS) is an extremely rare
      disorder in childhood. This report presents an 8-year-old female case of IACNS.
      She showed paresis at the right face and upper limb at the onset, followed by
      various focal neurological symptoms. Cranial T2-weighted magnetic resonance
      imaging revealed multiple subcortical high signal lesions, which appeared and
      disappeared in accordance with her clinical manifestations. The level of her
      plasma thrombin-antithrombin III complex (TAT) was high during the active phase
      of the illness and seemed to be a useful marker for the detection of vasculitis
      in the CNS. Complete remission was achieved by the combination therapy of
      prednisone and cyclophosphamide.

PMID- 8280448
TI  - [Three cases of hypofibrinogenemia induced by chemotherapy with a combination of
      synthetic ACTH and valproic acid].
AB  - Chemotherapy with a combination of synthetic ACTH (ACTH-Zn) and valproic acid
      (VPA) induced remarkable hypofibrinogenemia in three children (5 months, 8
      months, and 5 years and 10 months old) with intractable epilepsy. The lowest
      blood fibrinogen (Fbg) levels by this combination therapy were 22, 51 and 64
      mg/dl (mean 45.7 mg/dl), respectively. These levels occurred, when ACTH-Zn was
      administered at an average dose of 0.33 mg/day (0.03 mg/kg/day) and the mean
      blood concentration of VPA was 59.7 micrograms/ml. With the administration of VPA
      without ACTH-Zn, the lowest blood Fbg levels were 232, 108 and 170 mg/dl (mean
      170 mg/dl), respectively. The mean blood concentration of VPA was 109.0
      micrograms/ml. The inadvertent-effects associated with this combination therapy
      consisted of thrombocytopenia (59,000/microliters) in one case and a mild GPT
      increase (65-109 IU/l) in three cases. However, all these changes were transient.
      No bleeding tendency was detected clinically, when this hypo-Fbg-emia appeared.
      The concentration of VPA and the blood level of Fbg were found inversely
      correlated with a correlation coefficient of -0.22 (p < 0.01) in 150 serum
      samples from 91 patients with childhood epilepsy treated with VPA without ACTH
      Zn. In the three cases presented, the combination with ACTH-Zn resulted in
      considerably lower blood Fbg levels than those predicted from the blood VPA
      concentrations. This indicates that the combination of ACTH-Zn and VPA induces a
      further decrease of Fbg in blood. The reason why hypo-Fbg-emia results from this
      combination therapy is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID- 8280449
TI  - [A case of congenital muscular dystrophy associated with hydrocephalus--CSF
      dynamics and surgical treatment].
AB  - A case of Fukuyama-type congenital muscular dystrophy (FCMD) associated with
      hydrocephalus was reported. A 15-month-old male, diagnosed as FCMD at 4 months
      old, revealed progressing large head. CT scan and MRI indicated not only
      lissencephaly II classified by Dobyn, but dilated ventricular system and
      subarachnoid space, and these findings radiologically resembled those of brain
      atrophy. Intracranial pressure and CSF dynamics monitoring revealed high
      intracranial pressure and high CSF outflow resistance, indicating a high pressure
      hydrocephalus. V-P shunt made the patient improved not only symptomatically, but
      physiologically (increased CBF and decreased intracranial pressure and CSF
      outflow resistance). We concluded that the early diagnosis and treatment of
      hydrocephalus superimposing the organic disease may prevent secondary damage of
      the brain, and the intracranial pressure and CSF dynamics monitoring is essential
      for its diagnosis.

PMID- 8280450
TI  - [A case of clinical Reye syndrome with symmetrical abnormal signal areas in the
      pons and thalami by MRI].
AB  - We report a two-year-old boy with clinical Reye syndrome. Brain CT disclosed
      symmetrical low-density areas in the pons and thalami, a part of which was
      recognized as being of high-intensity on both T1 and T2 weighted MRI. These
      lesions were suspected of being caused by vascular involvement, since the
      methemoglobin induced by bleeding may have contributed to the high-intensity
      regions. The lesions gradually disappeared within four months after the onset,
      and clinical symptoms also improved markedly without serious neurologic
      impairment. This case was characterized by the marked improvement in neurological
      and radiological findings in spite of the serious neurological involvement at
      onset.

PMID- 8280451
TI  - [Brain perfusion in acute infantile hemiplegia studied with single photon
      emission computed tomography].
AB  - Sequential examinations of single photon emission computed tomography (SPECT)
      were performed on a 5-month-old boy with acute infantile hemiplegia from the
      acute ictal stage. SPECT was performed with technetium-99m-hexamethyl-propylene
      amineoxime during the status when the patient had left-hemiconvulsions (status
      epilepticus) and on the 3rd, 7th and 10th day after the status. During the ictal
      stage and the 3rd day after the status, diffuse hyperperfusion was revealed in
      the right hemisphere, while diffuse hypoperfusion was exhibited in the right
      hemisphere on the 7th and 10th day after the status. Hypoperfusion in the
      corresponding hemisphere, after the status, has been reported in patients with
      acute infantile hemiplegia. There has, however, been no report of ictal brain
      perfusion. The pathogenesis of this hyperperfusion is not clear, but alteration
      of brain perfusion in this patient, especially in acute phase, may help to
      elucidate the etiology of acute infantile hemiplegia.

PMID- 8280452
TI  - [A case of 15p tetrasomy associated with infantile spasms].
AB  - A seven-year-old boy with a 15p tetrasomy: [47, XY, + inv dup (15) (pter-->q13:
      :q13-->pter)] was reported. The clinical manifestation were as follows; infantile
      spasms, delayed development and slightly brownish coloured skin. But there were
      no other abnormal findings in neurological or physical examinations. This was the
      first case with 15p tetrasomy and infantile spasms.

PMID- 8280453
TI  - [A case of multiple intracerebral cavernous angioma presenting with seizures at
      the onset].

PMID- 8280454
TI  - [SPECT evaluation by acetazolamide test using 99m Tc-HMPAO in alternating
      hemiplegia of childhood].

PMID- 8280455
TI  - [Accidents in children with epilepsy--especially sudden unexpected death].

PMID- 8280456
TI  - [Characteristic MRI findings of sibling cases with Sjogren-Larsson syndrome].

PMID- 8280457
TI  - [A study on the causes of the physical and mental disabilities in children].
AB  - The causes and time of onset of physical and mental disabilities in children were
      investigated. Among 72 subjects, the causes of the disabilities were clearly
      verified in 43 cases, that is, 21 cases of hypoxic ischemic encephalopathy (29%),
      12 cases of cerebral malformations (17%), 7 cases of other congenital
      malformations (10%), and 3 cases of intrauterine infections (4%). In 10 cases
      from the remaining 29 subjects, the disorders during perinatal period were
      strongly suggested from the findings of CT and MRI.

PMID- 8280458
TI  - Cell mediated events that control blood coagulation and vascular injury.
AB  - Recent studies suggest that the generation of thrombin and other clotting factors
      plays a major role in cellular regulation and probably a variety of disease
      processes. Many of these cellular responses occur at thrombin levels lower than
      those required for fibrin clot formation. The availability of more specific
      reagents to intervene in the coagulation process will likely provide a better
      understanding of the role of the coagulation cascade and its inhibitors in normal
      and pathologic responses. In the immediate future, improved understanding of the
      role of inflammation and cellular responses in the control of coagulation offers
      many new and potentially safer interventions to prevent thrombosis. DISCLAIMER:
      It was my intent in this chapter to provide some outlines of the role of
      membranes in the blood clotting process and the role of coagulation factors in
      cellular activation. The scope of the area is so extensive that many important
      contributions have been overlooked and space limitations forced citation of
      reviews rather than primary publications in many cases. I regret these
      oversights.

PMID- 8280459
TI  - Signal-dependent membrane protein trafficking in the endocytic pathway.

PMID- 8280460
TI  - Assembly and intracellular transport of MHC class I molecules.

PMID- 8280461
TI  - Biology of animal lectins.

PMID- 8280462
TI  - Macromolecular domains within the cell nucleus.

PMID- 8280463
TI  - The spectrin-based membrane skeleton and micron-scale organization of the plasma
      membrane.

PMID- 8280464
TI  - Tumor necrosis factor, other cytokines and disease.

PMID- 8280465
TI  - Signal transduction in guard cells.

PMID- 8280466
TI  - Structure and function of the B cell antigen receptor.

PMID- 8280467
TI  - Life at the leading edge: the formation of cell protrusions.

PMID- 8280468
TI  - Protein import into peroxisomes and biogenesis of the organelle.

PMID- 8280469
TI  - Transcriptional repression in eukaryotes.

PMID- 8280470
TI  - Molecular aspects of mesenchymal-epithelial interactions.

PMID- 8280471
TI  - Tumor cell interactions with the extracellular matrix during invasion and
      metastasis.
AB  - Recent findings have produced great strides in developing an understanding of the
      molecular events involved in processes necessary for tumor cell invasion and
      subsequent metastasis formation. This information has been useful in developing
      new targets for therapeutic intervention such as disruption of tumor cell
      attachment by peptide analogues of cell adhesion molecules and the use of
      protease inhibitors to limit extracellular matrix proteolysis required for tumor
      cell invasion. Future efforts must focus on how the events of cell attachment,
      matrix proteolysis, and cell migration are controlled and integrated. This
      requires a better understanding of the transcriptional controls and cell
      signaling mechanisms that are involved in these events. Preliminary findings
      suggest that cell-matrix interactions influence gene expression and that the
      protease inhibitor balance can greatly influence cell-matrix interactions.
      Therefore it appears that all three steps in the invasive process are linked and
      interdependent. While this complicates the study of these processes, it is our
      belief that understanding this interdependence is critical for further
      development of metastasis research.

PMID- 8280472
TI  - The role of GTP-binding proteins in transport along the exocytic pathway.

PMID- 8280473
TI  - Role of the major heat shock proteins as molecular chaperones.

PMID- 8280474
TI  - Functional elements of the cytoskeleton in the early Drosophila embryo.

PMID- 8280475
TI  - Role of HIV-1 envelope V3 loop cleavage in cell tropism.
AB  - The envelope protein is an important determinant of HIV-1 cell-specific tropism.
      The gp160 envelope precursor proteins from macrophage-tropic or T lymphoid cell
      line-tropic strains of HIV-1 were expressed in recombinant vaccinia virus
      infected cell lines or primary lymphocytes or macrophages. No significant
      differences in the kinetics of synthesis of gp160, processing into gp120 and gp41
      proteins, N-linked glycosylation, or release of gp120 into the medium were noted
      with the different envelope proteins. However, gp120 envelope protein shed into
      the medium was found to be at least partially cleaved at a site within the V3
      loop. The gp120 envelope proteins from macrophage-tropic isolates exhibited lower
      rates of cleavage than those from lymphoid cell line-tropic strains in all cell
      types examined. Cell-free protease digestion studies also demonstrated relative
      resistance of the envelopes from macrophage-tropic compared to lymphoid cell line
      tropic strains. All recombinant envelope proteins were recognized by monoclonal
      antibodies directed at gp41 or the C-terminal gp120 epitopes, and no differences
      in binding to CD4 were noted.

PMID- 8280476
TI  - ETS family proteins activate transcription from HIV-1 long terminal repeat.
AB  - ets is a multigene family and its members share a common ETS DNA-binding domain.
      ETS proteins activate transcription via binding to a purine-rich GGAA core
      sequence located in promoters/enhancers of various genes, including several that
      are transcriptionally active in T cells. The ETS1, ETS2, and ERBG/Hu-FLI-1 gene
      expression pattern also suggests a role for these genes in cells of hematopoietic
      lineage. The HIV-1 LTR core enhancer contains two 10-base pair direct repeat
      sequences (left and right) that are required for regulation of HIV-1 mRNA
      expression by host transcription factors, including NF kappa B. Two ETS-binding
      sites are present in the core enhancer of all the HIV-1 isolates reported so far.
      In our studies, we utilized HIV-1 HXB2 and HIV-1 Z2Z6 core enhancers because the
      Z2Z6 strain has a single point mutation flanking the right ETS-binding site. We
      demonstrate that the ETS1, ETS2, and ERGB/Hu-FLI-1 proteins can trans-activate
      transcription from both the HXB2 and Z2Z6 core enhancer when linked to a reporter
      (cat) gene. In addition, we show that the DNA binding and trans-activation with
      the Z2Z6 core enhancer is at least 40-fold higher than that observed with the
      HXB2 core enhancer. Further, we provide evidence that the marked increase in
      binding and trans-activation with Z2Z6 core enhancer sequences is due to the
      substitution of a flanking T residue in HXB2 TGGAA) by a C residue in Z2Z6
      (CGGAA) isolate, thus generating an optimal ETS-binding core (CGGAA) sequence.

PMID- 8280477
TI  - The human immunodeficiency virus type 1 (HIV-1) vif protein is located in the
      cytoplasm of infected cells and its effect on viral replication is equivalent in
      HIV-2.
AB  - The human immunodeficiency virus type 1 (HIV-1) vif gene (viral infectivity gene)
      plays an important role in viral replication in vitro. We demonstrated that the
      Vif protein is membrane associated in HIV-1-infected cells and have investigated
      the role in viral replication of the equivalent gene in HIV-2. We constructed an
      HIV-2 vif minus mutant and studied its virulence and cellular tropism in vitro.
      Parallel experiments were also performed with an HIV-1 vif mutant to ascertain
      whether the two distantly related HIV-2 and HIV-1 genes might exert the same
      effect on viral replication. The results indicated that both HIV-1 and HIV-2 vif
      minus cell-free infection was not impaired when the SupT-1 cell line was used.
      However, differential degrees of impairment in viral replication were observed
      when other cell lines were used (Molt-3, U-937). Nevertheless, when viral
      production could not be detected, rescue experiments by coculture with the
      permissive cell line SupT-1 were generally positive, indicating that the viruses
      were still present in the inoculated cells. In contrast, when primary human cells
      (peripheral blood mononuclear cells and purified macrophages) were infected with
      HIV-1 and HIV-2 vif minus viruses no productive infection was observed and
      generally no virus was rescued by cocultivation. Thus, like in HIV-1, the vif
      gene of HIV-2 is crucial for viral infectivity in primary cells and might
      represent an attractive target for therapy.

PMID- 8280478
TI  - Further evidence of icosahedral symmetry in human and simian immunodeficiency
      virus.
AB  - Specimens of HIV and SIV have been examined by electron microscopy, using the
      techniques of conventional thin sectioning, freeze-substitution, cryosectioning,
      and cryomicroscopy of frozen hydrated specimens. In addition freeze-drying and
      critical point drying were used for both shadowed replicas and scanning electron
      microscopy. Thin sections revealed hexagonal, pentagonal, or near-spherical
      profiles. Angular particles were seen in shadowed replicas and also by scanning
      electron microscopy. The images observed were consistent with an icosahedral
      shape of the virus. It is proposed that mature HIV (SIV) is an icosadeltahedron
      with flat triangular facets. Size measurements of the specimens showed a wide
      range of values for conventional embedding, but a narrow range for specimens
      prepared by low-temperature techniques.

PMID- 8280479
TI  - Expression of HIV-1 envelope glycoproteins by Semliki Forest virus vectors.
AB  - We have used Semliki Forest virus (SFV) vectors to express both the human
      immunodeficiency virus type 1 (HIV-1) envelope precursor gp160 and the cleaved
      external portion gp120. Expression of the foreign gene in this system is by
      transfection of recombinant SFV RNA, or by infection with a recombinant SFV virus
      that has a wide host range. pSFV1-gp120 or pSFV1-gp160 were expressed in baby
      hamster kidney (BHK) cells and two human cell lines: HeLa cervical carcinoma and
      MOLT-4 CD4+ T cells. After SFV1-gp120 infection of HeLa cells, 3.3 micrograms of
      gp120 was secreted into the media by 1 million cells in a 24-hr period. The
      secreted envelope glycoprotein was recognized by anti-gp120 monoclonal antibodies
      directed against both linear and conformation-dependent epitopes in different
      regions of the molecule. The recombinant gp120 also bound to a soluble form of
      the CD4 receptor. Syncytium formation was observed when MOLT-4 cells were
      infected with SFV1-gp160. The gp160 expressed by BHK cells induced syncytia
      during cocultivation with C8166 CD4+ T cells. These data indicate that SFV
      vectors can be used to produce the HIV-1 envelope glycoproteins to high levels,
      and that these proteins are correctly processed, folded, and transported to the
      cell surface. Furthermore, they exhibit functional activity as indicated by their
      ability to bind to soluble receptor and induce cell-to-cell fusion.

PMID- 8280480
TI  - Immunization with recombinant gp160 prolongs the survival of HIV-1 transgenic
      mice.
AB  - A strain of mouse transgenic for the env gene of the HIV-1 virus was used to
      study the immunogenicity of a gp160-derived vaccine (the protein encoded by the
      HIV env gene) and its effect on disease progression. Untreated transgenic mice
      frequently developed a rapidly progressive renal disease similar to that
      affecting approximately 10% of HIV-infected humans. When transgenic mice were
      immunized with recombinant purified gp160, their edema, proteinuria, and serum
      BUN levels were substantially reduced and their survival prolonged (p < 0.01).
      The increased longevity of immunized transgenic mice correlated with the
      production of IgG antibodies reactive with gp160.

PMID- 8280482
TI  - Stage I testicular seminoma following orchidectomy--to treat or not to treat.

PMID- 8280481
TI  - Diversity of V3 region sequences of human immunodeficiency viruses type 1 from
      the central African Republic.
AB  - Nucleotide sequences of the central portion of gp120, including the third
      hypervariable (V3) loop, were obtained from lymphocytes cocultivated with SupT1
      cells from 29 AIDS patients in Bangui, Central African Republic. These sequences
      displayed significantly greater diversity (average distance, 23%) than has been
      previously observed in isolates from comparably restricted geographical areas.
      Isolates belonging to four major subtypes of HIV-1 were found; the only subtype
      not represented was the North American/European subtype B. Unlike the situation
      in Zaire and Uganda, where subtypes A and D account equally for virtually all
      isolates of HIV-1, the predominant subtypes in the Central African Republic,
      accounting for two-thirds of the isolates, were subtypes A (10 isolates) and E (9
      isolates). Subtype E represents a group of variants that have previously been
      found only in Thailand. Only one isolate belonging to subtype D was found. Also
      recovered were two isolates of subtype C, a subtype associated with southern
      African and Indian isolates but not previously detected in central Africa. These
      isolates, although clearly clustering with subtype C, formed a distinct subset,
      differing from one another by 8.8% and from the Indian and South African subtype
      C isolates by an average of 22.5%. High interpatient, intrasubtype variation was
      also seen among the CAR subtype A (average pairwise difference, 19.3%) and
      subtype E (10.9%) isolates. The diversity of V3 sequences in this set has
      implications for immunization protocols that rely on the recognition of V3. This
      study underscores the necessity of basing intervention strategies on knowledge of
      the particular sequences present in the target population or geographical area.

PMID- 8280483
TI  - Primary gastric non-Hodgkin's lymphoma: a therapeutic challenge.

PMID- 8280484
TI  - Surveillance following orchidectomy for stage I seminoma of the testis.
AB  - From 1985 to 1988, 261 unselected patients entered a nationwide Danish study of
      surveillance only for testicular seminoma stage I. The median follow-up time
      after orchidectomy was 48 months, range 6-67 months. 49 patients relapsed (19%).
      Sites of relapse were paraaortic lymph nodes in 41 patients, pelvic lymph nodes
      in 5, inguinal lymph nodes in 2 and lung metastases in 1 patient. The median time
      to relapse was 14 months, range 2-37 months. The 4-year relapse-free survival was
      80%. 37 of the relapsing patients (76%) had radiotherapy as relapse treatment. Of
      these patients, 4 (11%) had a second relapse and received chemotherapy. 1 died of
      disseminated seminoma. Of the relapsing patients, 12 (24%) had chemotherapy as
      relapse treatment because of bulky (11 patients) or disseminated disease (1
      patient). None of these patients have had a second relapse. However, 2 patients
      died of infection due to chemotherapy-induced neutropenia. Thus, there have been
      three seminoma-related deaths (1.1%). The testicular tumour size had an
      independent prognostic significance. The 4-year relapse-free survivals were 94,
      82 and 64% for tumours < 3, 3 to < 6 and > or = 6 cm, respectively. Patients with
      tumours > or = 6 cm will now be given prophylactic radiation treatment, whereas
      we will continue to use surveillance only after orchidectomy for patients with
      tumours < 6 cm.

PMID- 8280485
TI  - Expression of the tumour-associated antigen CA-242 in transitional cell bladder
      tumours: a comparison with CA-50.
AB  - The tissue expression of carbohydrate antigen CA-242 was analysed in formalin
      fixed biopsy specimens from 147 transitional cell bladder tumours. The staining
      was related to established prognostic factors and survival during a mean follow
      up of over 12 years and the staining results were also compared to expression of
      CA-50 antigen. Forty-one percent (60/147) of the tumours were negative for CA-242
      and 59% (87/147) were positive. Normal bladder mucosa was positive for CA-242 and
      the umbrella cells in particular showed intense positive staining. In tumours,
      the umbrella cells were usually positive (when present) and in tumour tissue,
      positive cells appeared either as individual positive cells or in groups. None of
      the tumours was entirely positive for CA-242. The tissue expression of CA-242
      could not be significantly related to TNM classification, papillary status, WHO
      grade or quantitative variables (DNA ploidy, S phase fraction, mitotic frequency,
      nuclear factors). The tissue expression of CA-242 was significantly weaker than
      the expression of CA-50. The expression of CA-242 was related to favourable
      prognosis in survival analysis (P = 0.04). The results show that the expression
      of the novel tumour marker antigen CA-242 as determined in paraffin-embedded
      material is a weak prognostic factor as compared with established prognostic
      factors in transitional cell bladder tumours.

PMID- 8280486
TI  - Selection of large and objectively measurable target lesions in EORTC phase II
      trials: impact on recruitment and response rate. EORTC Soft Tissue and Bone
      Sarcoma Group (STBSG).
AB  - The EORTC has recently issued minimum requirements for target lesions in phase II
      trials, aiming at a decrease in measurement errors [minimum size, computer
      tomography (CT) scan or ultrasound for deep lesions]. Their impact on recruitment
      and response has been retrospectively studied in a trial of the EORTC Soft Tissue
      and Bone Sarcoma Group (STBSG), investigating high-dose chemotherapy in patients
      with advanced soft tissue sarcoma, where 46/103 objective responses were seen,
      including 10 complete responses. For the 20 patients who did not satisfy the
      criteria, a similar objective response rate and a significantly higher complete
      response rate were reported. Among 265 target lesions, the same trends were
      observed when comparing small to large lesions, for different tumour sites. For
      deep lesions clinically assessed, significantly higher response rates were
      reported than for those measured by CT scans or ultrasound. The new stricter
      EORTC criteria improve the reliability of measurements and have been adopted for
      future phase II trials of the STBSG. This will not result in the selection of
      potentially poor responders. Less than 20% of the present recruitment will be
      lost.

PMID- 8280487
TI  - Increased frequency of lymphocyte depletion and mixed cellularity subtypes of
      Hodgkin's disease in HIV-infected patients. Italian Cooperative Group on AIDS and
      Tumours.
AB  - To assess whether the histological pattern of Hodgkin's disease (HD) in human
      immunodeficiency virus (HIV)-infected patients differs from that among HD
      patients without HIV infection, the observed (O) number of HD cases according to
      histological subtype [i.e. lymphocyte predominance (LP), nodular sclerosis (NS),
      mixed cellularity (MC) and lymphocyte depletion (LD)] among 92 Italian HIV
      infected patients was compared with the expected (E) number derived from two case
      series of HD from Europe and the U.S.A. (14,315 cases of HD) and Italy (125
      cases). After age standardisation, the O/E ratio was computed, along with its 95%
      confidence interval (CI). In comparison with 125 Italian HD patients not infected
      with HIV, a 4-fold higher frequency of the MC histological subtype (95% CI: 2.9
      5.1) and an approximately 12-fold higher frequency of the LD subtype (95% CI: 7.0
      18.0) emerged among HIV-infected patients. These results were substantially
      confirmed when the comparison was made with the case series from Europe and the
      U.S.A. These data show different histological patterns of HD between a group of
      HIV-infected patients and HD patients from the general population. Although
      caution is needed in their interpretation, the study results seem to indicate
      that HD of the MC or LD subtypes may be considered an AIDS-related malignancy.

PMID- 8280488
TI  - The prognostic value of epidermal growth factor receptors, determined by both
      immunohistochemistry and ligand binding assays, in primary epithelial ovarian
      cancer: a pilot study.
AB  - After our previous studies on the incidence of epidermal growth factor receptors
      (EGF-R) and its relationships with other tumour characteristics in more than 100
      ovarian tumours, in the present study we investigated the prognostic value of EGF
      R with respect to progression-free survival in 50 patients with primary ovarian
      cancer and sufficient follow-up (median 26 months, range 10-33 months). EGF-R was
      measured by both biochemical and two immunohistochemical methods, using two
      monoclonal antibodies (MAb), in addition to oestrogen receptors (ER) and
      progesterone receptors (PgR). EGF-R by ligand binding assay and Scatchard
      analysis were detectable in 63% of the tumours, by immunohistochemistry with MAb
      2E9 in 82% and with MAb EGF-R1 in 78% of the tumours. ER-positivity was found in
      58% and PgR-positivity in 38% of the patients. The results of the three
      measurements of EGF-R showed only weak to moderate associations with Spearman
      rank correlations (Rs) between 0.13 and 0.46. ER and PgR were only weakly
      correlated (Rs = 0.20) and they showed no significant association with EGF-R
      status. There was no clear evidence of the existence of correlations between
      receptor values and FIGO stage and tumour rest. Univariate Cox regression
      analyses showed that a higher FIGO stage and larger tumour rest were associated
      with shorter progression-free survival (P = 0.001), while PgR positivity was
      associated with a longer progression-free survival (P = 0.02). The level of EGF-R
      (irrespective of the method of determination used) showed a positive correlation
      with the risk of progression, but this correlation was not statistically
      significant.

PMID- 8280489
TI  - Evidence for abrogation of oncogene-induced radioresistance of mammary cancer
      cells by hexadecylphosphocholine in vitro.
AB  - Hexadecylphosphocholine (HePC), an experimental and clinical antitumour agent of
      the alkyllysophospholipid group, was tested for its radiosensitising effect on a
      panel of nine human mammary cancer cell lines in vitro. Growth inhibition by
      ionising radiation and recovery from it were not influenced by pretreatment with
      HePC in most cases, except for two cell lines expressing an activated ras
      oncogene. In the latter we found an enhanced radioresistance that was abolished
      by pretreatment with HePC. Our results suggest that HePC may act as a
      radiosensitiser for cells carrying an activated ras oncogene.

PMID- 8280490
TI  - HLA expression in pre-invasive cervical neoplasia in relation to human papilloma
      virus infection.
AB  - A significant proportion of cervical carcinomas show loss of major
      histocompatibility complex human leucocyte antigen (HLA) class I expression while
      upregulating HLA class II expression. These changes may have direct consequences
      for immune surveillance of the human papilloma virus (HPV) infection which is
      strongly associated with cervical malignancy. A relationship between changes in
      HLA expression and HPV infection may be evident in the evolution of premalignant
      disease. This immunohistological study of 104 colposcopic biopsies establishes
      that HLA class II expression occurs in a significant proportion of squamous
      epithelia showing histological evidence of wart virus infection and cervical
      intraepithelial neoplasia (CIN) I to III. In comparison, alteration of HLA class
      I expression in cervical premalignant lesions is rare. There is no correlation
      between the detection of high risk HPV DNA (types 16, 18, 31 and 33) by
      polymerase chain reaction (PCR) and the MHC class II phenotype of the lesion.
      This suggests that altered HLA class II expression is neither a consequence nor a
      prerequisite for HPV infection.

PMID- 8280491
TI  - Does long-term administration of tamoxifen affect bone mineral density?
AB  - A retrospective study was performed to determine whether the long-term (5 years
      or more) administration of tamoxifen is detrimental to bone mineral density
      (BMD). 19 patients taking adjuvant tamoxifen for breast cancer were paired with
      19 controls comparable in age, time since menopause and performance status. BMD
      was measured at the femoral neck, lumbar spine and total body by dual energy X
      ray absorptiometry (DEXA). There was no detrimental effect on BMD at any site.
      There was a trend towards an increase in BMD at the femoral neck. There were
      minor decreases in the serum calcium, phosphate and alkaline phosphatase.

PMID- 8280492
TI  - Reconstitution of recombinant interleukin-2 (rIL-2): a comparative study of
      various rIL-2 muteins.
AB  - In a previous clinical study using a continuous infusion schedule of recombinant
      interleukin-2 (rIL-2) we noted a nearly complete loss of activity of EuroCetus
      rIL-2 when dissolved in 10 ml saline and infused at a very low rate through a
      plastic infusion device. In the present study, we demonstrated that the loss
      resulted from a concentration-dependent precipitation of rIL-2 in saline and
      adherence of the protein to the tubing material. These phenomena were not noted
      for four other rIL-2 muteins tested [Glaxo, Hoffmann-LaRoche, Amgen (2 muteins)].
      EuroCetus rIL-2 was found to be completely soluble in water and 5% glucose.

PMID- 8280493
TI  - Biochemical characterisation of elsamicin and other coumarin-related antitumour
      agents as potent inhibitors of human topoisomerase II.
AB  - Elsamicin (EM) is a recently discovered antitumour agent that is structurally
      related to several other compounds displaying anticancer activities, including
      chartreusin (CT), chrysomycin V (CV) and M (CM), gilvocarcin V (GV) and
      ravidomycin (RM). The biochemical events resulting in cytotoxicity for most of
      these compounds have not been clearly elucidated. There is some evidence that GV
      and CT bind to DNA and that GV is photosensitive, causing DNA damage. Therefore,
      we investigated the effects of these chemicals on DNA in cells and on pBR322
      plasmid DNA. Using alkaline elution techniques, we found that all these compounds
      induced, to a different extent, DNA breakage in the human lung adenocarcinoma
      A549 cell line. In addition, all either bound to or intercalated into DNA, as
      indicated by their ability to alter the electrophoretic migration of DNA in
      agarose gels. Using the P4 unknotting assay, EM, CT, CV, CM, GV and RM were found
      to be potent inhibitors of the catalytic activity of topoisomerase II (topo II).
      Their potencies were compared with the known topo II inhibitors teniposide (VM
      26) and doxorubicin (DX). EM was the most potent, with an IC50 of 0.4 mumol/l
      followed in order by CV, GV, and CT. VM-26 was the least potent with an IC50 of
      15 mumol/l. It was concluded from these results that EM, GV, CV, CM and CT are
      capable of inhibiting topo II and that EM is the most potent inhibitor of topo II
      yet discovered.

PMID- 8280494
TI  - Amplified met gene linked to double minutes in human glioblastoma.
AB  - The met proto-oncogene was found to be amplified in a human glioblastoma cell
      line (T3095) established from a glioblastoma multiform WHO grade IV.
      Amplification of epidermal growth factor receptor, transforming growth factor
      alpha and N-myc which have been described previously in glioblastoma were not
      observed in T3095. There was, however, an 8-fold met amplification. Giemsa
      stained metaphases of T3095 cells revealed multiple (> 5) double minutes (dmins)
      in the majority of cells. Following xenografting in nude mice there was a
      significant increase in the number and frequency of dmins. The increase in dmins
      correlates with the level of met amplification (50-fold), suggesting localisation
      of the amplified met on dmins. Here we report the first case of met amplification
      in glioblastoma. Correlation between met amplification and extrachromosomal
      elements (dmins) has not been reported previously.

PMID- 8280495
TI  - CD44 is associated with proliferation in normal and neoplastic human colorectal
      epithelial cells.
AB  - Flash-frozen biopsies obtained from surgical specimens of three adenomatous
      polyps and 22 colorectal adenocarcinomas (19 primary and three metastatic) were
      tested by immunohistochemistry for CD44 expression using F10-44-2 monoclonal
      antibody. CD44 positivity was correlated with proliferative status defined by Ki
      67 monoclonal antibody reactivity. In normal colonic mucosa, CD44 was expressed
      in the proliferative zone of crypts. In tumours, CD44 expression was associated
      with proliferative areas irrespective of tumour stage or differentiation. Non
      proliferating areas of the carcinomatous epithelium did not express CD44 although
      non-proliferating stromal lymphoid tissue did. There was no apparent association
      with tumour progression. F10-44-2-defined CD44 is consistently expressed during
      proliferation by normal colorectal epithelial cells and by both benign and
      malignant colorectal tumour cells.

PMID- 8280496
TI  - Involvement of T lymphocytes in curative effect of a new immunomodulator OM 163
      on rat colon cancer metastases.
AB  - In a model of colon cancer in syngeneic rats, a new immunomodulator, OM 163,
      induced the complete disappearance of peritoneal carcinomatosis (nodules
      measuring 1-5 mm) in 41 out of 82 rats. Those results were confirmed in a
      survival experiment in which 3 out of 10 treated rats died free of tumour 10, 18
      and 28 months after the tumour cell injection while all the untreated control
      rats died of their tumours within 3 months. OM 163 had a systemic effect, since
      injected intraperitoneally it completely inhibited the growth of lung metastases
      in 13 out of 20 rats. The antitumour effect of OM 163 was also observed in two
      rat strains on original tumours. Lymphocyte infiltration was observed in the
      tumours mainly constituted of CD4+ and CD8+ cells. The treatment had no effect in
      nude rats, confirming the involvement of T lymphocytes. Furthermore, rats cured
      by OM 163 were protected against a second challenge of tumour cells and in a
      Winn's assay, splenocytes from cured rats protected normal rats against tumour
      cells.

PMID- 8280497
TI  - Serum beta-lipoprotein, serum cholesterol and Quetelet's index as predictors for
      survival of breast cancer patients.
AB  - We studied the survival of breast cancer patients in relation to serum
      cholesterol level, serum beta-lipoprotein level (BLP) and being overweight among
      women having breast cancer diagnosed during a follow-up period of 20 years. A
      cohort of 46,570 women attended a general health screening including examination
      of serum lipid levels, height and weight during 1963-1965. Of these, 1170 women
      developing breast cancer; 196 were below the age of 50 and 974 were above 50
      years of age. 66 of the younger women, and 341 of the older women were reported
      to have died of breast cancer. A correlation was found between high serum BLP and
      decreased survival of breast cancer patients < 50 years of age. For women > or =
      60 years of age, BLP was positively correlated to breast cancer survival. No
      correlation was found between serum cholesterol level and breast cancer survival
      in any age group. Increasing obesity was statistically significantly correlated
      to decreased survival with breast cancer. The latter findings were in accordance
      with other studies which have shown being overweight as a risk factor for breast
      cancer. As for the relationships between ischaemic heart disease and serum lipid
      levels, in studies of cancer risks in relation to serum cholesterol level, the
      different fractions of cholesterol seem to be of importance.

PMID- 8280498
TI  - Mutagens, N-nitroso compounds and their precursors in gastric juice from patients
      with and without precancerous lesions of the stomach.
AB  - This study examined whether elevated risk of gastric cancer is associated with
      high levels of total N-nitroso compounds (NOC), their precursors and nitrosation
      dependent genotoxins in gastric juice (GJ). An improved method for quantifying
      total NOC was used and genotoxicity was assayed in E. coli. Results from patients
      (n = 210) with or without precancerous lesions of the stomach and living in three
      areas with up to 8-fold variations in gastric cancer risk (U.K., France,
      Colombia) were compared. The level of nitrite (range < 1-472 mumol/l) was found
      to increase with the pH of GJ from the three countries and was dependent on
      country of collection. The levels of NOC (range: < or = 0.01-8.0 mumol/l) in GJ
      were not affected by stomach histology and country of collection. NOC levels
      increased linearly with nitrite concentrations, but the slope of the regression
      line was greater for acidic GJ (pH < or = 4). These data together suggest that
      chemical nitrosation contributes at least as much as other nitrosation pathways
      to the intragastric formation of NOC. Acid-catalysed nitrosation of GJ in vitro
      increased the NOC concentration (range: 7-1332 mumol/l) up to several 1000-fold
      but this increase was not predictive of gastric cancer risk either by country or
      by stomach histology. After acid-catalysed nitrosation, direct genotoxicity (SOS
      inducing potency) was significantly higher in GJ with original pH > 4 and highest
      in samples from Colombia. The results (a) provide no support that intragastric
      total NOC levels are elevated in subjects with precancerous stomach lesions or
      living in a high risk area for stomach cancer; (b) confirm that a high nitrite
      level and elevated pH in GJ are strongly associated, the level of nitrite being
      associated with precancerous stomach conditions only in Colombia; (c) reveal the
      presence of precursor compounds in GJ, that after nitrosation yield direct
      mutagens that probably contain NOC and other substances. As their concentrations
      were significantly higher in achlorhydric subjects and highest in Colombian
      patients, these data together provide support for a role of intragastrically
      formed nitrite-derived direct mutagens in gastric cancer aetiology.

PMID- 8280499
TI  - Study of the role of breast self-examination in the reduction of mortality from
      breast cancer. The Russian Federation/World Health Organization Study.
AB  - The protocol of a study, sponsored by the World Health Organization, of the role
      of breast self-examination (BSE) in reduction of mortality from breast cancer is
      presented. The major objective of the study is to determine the effect of a BSE
      programme on mortality from breast cancer. A population of of over 193,000 women
      aged 40 to 64 has been defined in Moscow and St Petersburg and randomised to
      study and control groups. In Moscow the education programme is based on a two-way
      communication principle allowing efficient person-to-person education in groups
      of up to 20 individuals and feedback information through specially designed
      personal calendars. In St Petersburg, class and individual instruction is carried
      out. After a 1-year feasibility study the project is planned to last for 15
      years. It consists of an aggressive education programme, during and following
      which, all newly diagnosed breast cancers will be registered and treated, and
      followed up for 3 to 15 years. A key issue of the study is compliance of the
      population with BSE. The frequency and competence of BSE practice has been
      defined in subsamples of 400 randomly selected women by means of surveys at 6
      months, 1, 2 and 3 years after the start of the project. The study is expected to
      result in the accrual of more than 1470 new breast cancer cases and 778 deaths
      from breast cancer. The power of the study is expected to permit detection of a
      30% reduction in cumulative breast cancer mortality, assuming that 50-70% of the
      women in the study group practise BSE.

PMID- 8280500
TI  - Retinoid receptors and acute promyelocytic leukaemia.
AB  - While a great deal has been learned about APL over the last few years, many
      important questions remain unanswered. It has become clear that the PML/RAR-alpha
      fusion protein is expressed in most cases of APL, and this protein presumably
      contributes to leukaemia initiation and/or progression. PML/RAR-alpha appears to
      specifically block the further differentiation of myeloid progenitor cells,
      although the mechanism of its action is not known. It may inhibit the
      transcription of RAR- or PML-regulated genes, in which case expression must be
      restored in the presence of therapeutic RA concentrations. However, the
      possibility remains that PML/RAR-alpha may have a novel function. In order to
      elucidate the molecular pathogenesis of APL, several important questions remain
      to be answered. These include whether PML is a transcription factor; the
      identification of its target genes and response elements, and the role of PML/RAR
      alpha and RA in their regulation. Also whether the expression of PML/RAR-alpha in
      bone marrow cells (either by itself or in combination with other oncogenes)
      alters their tumourigenicity or differentiation potential. It is also important
      to determine the function(s) of PLZF and PLZF/RAR-alpha, and determine whether
      other APL patients with mutations involving PML or RAR-alpha (but not both)
      respond to therapy with all-trans-RA. Finally, it is important both for the
      understanding of the molecular biology of APL and its therapy, to determine the
      effects of other regulatory factors involved in the control of myeloid cell
      differentiation such as granulocyte colony stimulation factor (G-CSF) and
      granulocyte macrophage colony stimulating factor (GM-CSF) on APL cells in vitro
      and in vivo, both at presentation and in the RA-resistant patients in relapse.

PMID- 8280501
TI  - The molecular biology of soft tissue sarcomas.

PMID- 8280502
TI  - Environmental tobacco smoke and the risk of cancer in adults.
AB  - The apparent effect of environmental tobacco smoke (ETS) exposure on cancer risk
      has become an important social and political issue. The risk of cancer in non
      smokers is often the main reason for prohibiting or restricting smoking in public
      places. A number of epidemiological studies have shown an association between ETS
      exposure and lung cancer. However, the strength of this association has still to
      be estimated. Only a few studies have reported on ETS and cancer from sites other
      than the lung in adults. No definite conclusions can be drawn at present from a
      critical review of the epidemiological evidence, but the suggestion of an
      association is present for sinonasal cancer, while bladder cancer does not seem
      to be associated to ETS exposure. Positive studies are available for cancers from
      other sites, including the breast, the uterine cervix and the brain, but these
      are difficult to interpret.

PMID- 8280503
TI  - Immunohistochemical expression of oncofetal fibronectin in benign and malignant
      lesions of the stomach.

PMID- 8280504
TI  - Delayed thyroid-stimulating hormone suppression by L-thyroxine in the management
      of differentiated thyroid carcinoma.

PMID- 8280505
TI  - Hyponatraemia secondary to administration of ifosfamide.

PMID- 8280506
TI  - Research by committee: a format to organize and conduct studies.
AB  - Research by committee is a relatively new format to conduct research projects.
      Since this format is best suited for projects that are multifaceted, the conduct
      of clinical validation studies of nursing diagnosis, which requires the input of
      educators, clinical experts and researchers, is possible. In order to conduct
      research by committee effectively, several dimensions must be considered such as
      how to form and coordinate a committee, as well as how to use resources,
      distribute workload, and motivate members. The author offers attributes of
      research by committee and a practical guide for optimally utilizing a committee
      format for the conduct of studies.

PMID- 8280507
TI  - You make the diagnosis: case study--two-year-old Bess and her family.

PMID- 8280508
TI  - The spiritual dimension of individuals: conceptual development.
AB  - The concept of spirituality (the spiritual dimension of an individual) is
      discussed related to concept development using the Path Associated with
      Differences. Spirituality is discussed as being different from religion and the
      psychosocial dimension of individuals. Methods for concept development--e.g.,
      concept derivation, intuition, and qualitative analysis--are explored.

PMID- 8280509
TI  - The relationships among nursing diagnoses in discharge planning for patients with
      lung cancer.
AB  - An explanatory study was designed to investigate whether nursing diagnoses
      present at discharge from the hospital accurately describe the complexity of care
      required in the community. A sample of 196 patients with lung cancer referred to
      community agencies at discharge was described by types of nursing diagnoses;
      types of agencies needed and services required; and by age, gender, race,
      economic status, and hospital length of stay. Using multiple logistic regression,
      a model for home care referral resulted in four significant predictor diagnoses:
      altered nutrition: less than body requirements, bathing/hygiene self-care
      deficit, high risk for infection, and high risk for injury. The model for hospice
      referral resulted in four significant predictor diagnoses: anticipatory grieving,
      impaired skin integrity, high risk for impaired skin integrity, and pain. The
      data suggest that the nursing diagnoses described the discharge planning needs,
      which predicted the type of agency referral needed.

PMID- 8280510
TI  - Conceptual and research-based validation of nursing diagnoses: 1950 to 1993.
      NANDA Research Committee.

PMID- 8280511
TI  - Imaging the dissected aorta.

PMID- 8280512
TI  - Anthracyclines and the heart.

PMID- 8280513
TI  - Assessment by general practitioners of suitability of thrombolysis in patients
      with suspected acute myocardial infarction.
AB  - OBJECTIVE: To assess the clinical ability of general practitioners to decide to
      give thrombolytic therapy to patients with suspected myocardial infarction and to
      assess the contribution of the electrocardiograph (ECG) to this decision-making
      process. SETTING: 7 practices on the North side of Glasgow and the coronary care
      unit of Stobhill General Hospital. SUBJECTS: 137 patients presenting with chest
      pain who required direct admission to the coronary care unit. MAIN OUTCOME
      MEASURES: Agreement between the general practitioner's clinical decision to give
      thrombolytic therapy with or without reference to the ECG and the prescription of
      thrombolytic therapy in the coronary care unit. RESULTS: The predictive accuracy
      of the general practitioner's assessment of the necessity for thrombolytic
      therapy was 71.5%. The ECG had no impact on the accuracy of this decision and
      there were problems with the recording and interpretation of the ECG. Clinical
      decision making was altered in six cases by the ECG: wrongly in four. CONCLUSION:
      The diagnostic accuracy among general practitioners would result in some patients
      who did not have acute myocardial infarction being given thrombolytic therapy. In
      this study the ECG did not contribute towards diagnostic accuracy. Substantial
      improvement in both the recording and interpretation of ECGs is needed before
      thrombolytic agents can be routinely prescribed at home.

PMID- 8280514
TI  - Rate of change of left ventricular ejection fraction during exercise is superior
      to the peak ejection fraction for predicting functionally significant coronary
      artery disease.
AB  - OBJECTIVE: To detect and characterise rapid temporal changes in the left
      ventricular response to exercise in patients with ischaemic heart disease and to
      relate these changes to the functional severity of coronary artery disease.
      BACKGROUND: The gamma camera does not allow the detection of rapid changes in
      cardiac function during exercise radionuclide ventriculography, the monitoring of
      which may improve the assessment of patients with ischaemic heart disease.
      METHODS: A miniature nuclear probe (Cardioscint) was used to monitor continuously
      left ventricular function during exercise in 31 patients who had coronary
      angiography for suspected coronary artery disease. A coronary angiographic
      jeopardy score was calculated for each patient. RESULTS: The coronary jeopardy
      score ranged from 0 to 12 (median 4). Ejection fraction fell significantly during
      exercise from 46% to 34%. Patients were divided into two groups based on the
      response of their ejection fraction to exercise. In 14 patients (group I), the
      peak change in ejection fraction coincided with the end of exercise, whereas in
      the other 17 patients (group II) the peak change in ejection fraction occurred
      before the end of exercise, resulting in a brief plateau. The peak change in
      ejection fraction and the time to its occurrence were independent predictors of
      coronary jeopardy (r = -0.59, p < 0.001 for peak change and r = -0.69, p < 0.001
      for time to that change). The rate of change in ejection fraction was the
      strongest predictor of coronary jeopardy (r = -0.81, p < 0.001). In group I the
      peak change in ejection fraction was a poor predictor severity of coronary
      disease (r = -0.28, NS), whereas the time to peak and the rate of change in
      ejection fraction were good predictors (r = -0.65 and r = -0.73, p < 0.01). In
      group II the peak, the time to the peak, and the rate of change in ejection
      fraction were good predictors of coronary jeopardy (r = -0.75, r = -0.61, and r =
      -0.83, p < 0.01). CONCLUSION: The rate of change of ejection fraction during
      exercise can be assessed by continuous monitoring of left ventricular function
      with the nuclear probe, and is the best predictor of functionally significant
      coronary artery disease.

PMID- 8280516
TI  - Linoleic acid and risk of sudden cardiac death.
AB  - OBJECTIVE: To test the hypothesis that the essential fatty acid, linoleic acid,
      measured in adipose tissue as an indicator of long term dietary intake, is
      inversely related to the risk of sudden cardiac death. DESIGN: A population case
      control study. SETTING: A regional health district. SUBJECTS: 84 men (age 25-64
      years) who died instantaneously or within 24 hours of the onset of symptoms with
      no history of coronary heart disease or medically treated hyperlipidaemia, and in
      whom coronary artery disease was diagnosed at postmortem examination as the
      primary cause of death, were compared with 292 age (to within two years) and sex
      matched healthy controls and their partners drawn from the general practitioners'
      records with whom the cases were registered. MAIN OUTCOME MEASURES: Fatty acid
      composition of adipose tissue and the risk of sudden cardiac death. RESULTS:
      Linoleic acid in adipose tissue was inversely related to the risk of sudden
      cardiac death. The estimated relative risk (95% CI) of sudden cardiac death was
      5.7 (1.8 to 17.9) for the lowest quintile and 4.0 (1.2 to 12.9) for the next
      quintile of adipose linoleic acid in the control population when compared with
      the highest quintile. This inverse relation was independent of age, reported
      smoking habits, history of hypertension, and diabetes, although there was a close
      association with cigarette smoking. The estimated adjusted proportionate increase
      in risk (95% CI) of sudden cardiac death was 1.14 (1.03 to 1.23) for every 1%
      reduction of linoleic acid in adipose tissue. CONCLUSIONS: The percentage content
      of linoleic acid in adipose tissue was inversely related to the risk of sudden
      cardiac death. Populations with a high risk of sudden cardiac death may benefit
      from increasing their dietary intake of polyunsaturated fatty acid oils,
      principally from cereals and vegetables.

PMID- 8280515
TI  - Coronary flow reserve in patients with chest pain and normal coronary arteries.
AB  - BACKGROUND: Many studies have shown that coronary flow reserve is reduced in
      patients with chest pain and angiographically normal coronary arteries. The
      methods used to assess coronary blood flow have varied, but in nearly all reports
      dipyridamole has been used to bring about vasodilatation. This study was designed
      to assess whether the apparent impairment of coronary flow reserve seen with
      dipyridamole could be reproduced with either papaverine or adenosine, which
      induce maximum coronary blood flow by different mechanisms. METHODS: 25 patients
      with chest pain and angiographically normal coronary arteries were studied with
      an intracoronary Doppler flow probe and quantitative angiography to determine
      epicardial coronary artery area, coronary blood flow velocity, coronary flow
      reserve, and coronary vascular resistance index (CVRI, the ratio of resistance
      after intervention to basal resistance). All patients received papaverine 8 mg.
      Eight patients with positive exercise tests received intracoronary papaverine (8
      and 10 mg), intracoronary adenosine (6, 20, 60 micrograms), and high-dose
      intravenous dipyridamole (0.84 mg/kg). RESULTS: The velocity ratio (peak after
      intervention: baseline) (mean (SEM)) after 8 mg papaverine was 3.3 (0.2) (n = 25)
      and the coronary flow reserve was 4.1 (0.3) (n = 25). There were no differences
      between patients with a positive (n = 16) or negative (n = 9) exercise test. In
      eight patients coronary flow reserve was measured after increasing doses of
      papaverine, adenosine, and dipyridamole. Coronary flow reserve was 4.5 (0.3) with
      papaverine, 4.8 (0.3) with adenosine, and 3.5 (0.4) with dipyridamole (p = 0.08 v
      papaverine and adenosine). CVRI was 0.22 (0.01) with papaverine, 0.21 (0.02) with
      adenosine, and 0.29 (0.03) with dipyridamole (p < 0.05 v papaverine, p = 0.09 v
      adenosine). CONCLUSIONS: These results indicate that measurement of coronary flow
      reserve and CVRI in patients with chest pain and normal coronary arteries depends
      on the pharmacological stimulus. Normal values were obtained with papaverine in
      all patients, irrespective of the exercise test response. In patients with a
      positive exercise test significantly lower values were obtained with dipyridamole
      than with papaverine, or adenosine. The reported impairment of coronary flow
      reserve in patients with angina and normal coronary arteries may reflect the
      variability in response to different pharmacological agents. The mechanism
      underlying this variability is unknown, but may involve an abnormality of
      adenosine metabolism in the myocardium.

PMID- 8280517
TI  - Enzymatic evidence of impaired reperfusion in diabetic patients after
      thrombolytic therapy for acute myocardial infarction: a role for plasminogen
      activator inhibitor?
AB  - OBJECTIVE: To compare the activity of plasminogen activator inhibitor (PAI-1) in
      diabetic and non-diabetic patients admitted with acute myocardial infarction and
      to determine whether PAI-1 activity influences reperfusion after thrombolytic
      therapy. DESIGN: Prospective study of patients admitted with acute myocardial
      infarction. SETTING: District general hospital. MAIN OUTCOME MEASURES:
      Reperfusion assessed by time to peak release of creatine kinase-MB isoenzyme.
      RESULTS: Baseline PAI-1 activity and antigen concentrations were significantly
      higher in diabetic patients (n = 45) than in non-diabetic patients (n = 110)
      (24.6 (6.9) v 18.6 (7.9) AU/ml (AU = arbitrary units) (p = 0.0001) and 58.8 (13.1
      328.8) v 41.0 (10.9-125.4) ng/ml (p = 0.004). Time to peak release of creatine
      kinase-MB was calculated in 123 (80%) patients. In 98 who received thrombolytic
      therapy the median time to peak enzyme release was 15.5 h (7.5-24 h) in diabetic
      patients (n = 26) and 12 h (5-26 h) in non-diabetic patients (n = 72) (p =
      0.005). In those with a time to peak release of < or = 12 h, indicating likely
      successful reperfusion, PAI-1 activity was 17.5 (7.8) AU/ml compared with 22.8
      (7.7) AU/ml in those with a time to peak release of > 12 h (p = 0.001). In
      multiple regression analysis both diabetes (p = 0.0001) and PAI-1 activity at
      admission (p = 0.029) were independently related to successful reperfusion. In 13
      patients with evidence of reinfarction in hospital PAI-1 activity on day 3 was
      26.7 (6.4) AU/ml compared with 21.7 (6.3) AU/ml in those without evidence of
      reinfarction (p = 0.032). CONCLUSION: Both raised PAI-1 activity on admission and
      diabetes were associated with a reduced likelihood of enzymatic evidence of
      reperfusion after thrombolytic therapy. Increased PAI-1 activity on day 3 was
      associated with an increased risk of reinfarction. Diabetic patients had higher
      PAI-1 activity on admission. This may partly explain their reduced likelihood of
      reperfusion.

PMID- 8280519
TI  - Effect of aortic valve replacement on syncope in patients with aortic stenosis.
AB  - OBJECTIVE: To determine the role of exertion as a precipitating factor in syncope
      in patients with aortic stenosis. DESIGN: Follow up for at least one year after
      aortic valve replacement. SETTING: Regional cardiac centre. PATIENTS: Consecutive
      patients who underwent aortic valve replacement for aortic stenosis and who had a
      history of syncope and no other clinically significant cardiac lesion were
      recruited during a five year period. METHODS: Patients were interviewed to
      determine the characteristics of syncope and were divided into those in whom
      syncope was consistently related to exertion (group 1, 26 patients) and those in
      whom it was not (group 2, 13 patients). Recurrence of syncope after valve
      replacement was determined at visits to the clinic. RESULTS: Groups 1 and 2 did
      not differ significantly with respect to valve area, age, or sex. In 13 of the 26
      patients in group 1 syncope was preceded by angina despite the absence of
      coronary artery disease, but none of the 13 patients in group 2 had angina. After
      valve replacement none of group 1 and eight of the 13 patients in group 2 had
      recurrence of syncope (p < 0.01). CONCLUSION: When patients with aortic stenosis
      experience syncope unrelated to exertion, the symptom is usually unrelated to the
      valve disease and another cause should be sought.

PMID- 8280518
TI  - Primary pulmonary hypertension and fenfluramine use.
AB  - Not all the risk factors for primary pulmonary hypertension (PPH) are known.
      Appetite suppressants, including fenfluramine derivatives, are strongly suspected
      aetiological agents. In a 5 year retrospective study fenfluramine use was
      evaluated among patients referred to a medical centre specialising in the
      management of PPH. Fifteen (20%) of 73 patients with PPH had used fenfluramine:
      all of them were women and in 10 (67%) there was a close temporal relation
      between fenfluramine use and the development of exertional dyspnoea. Initial
      right heart catheterisation in the 15 women showed severe resting pulmonary
      hypertension (mean (SD)) with pulmonary artery pressure (PAP) 57 (9) mm Hg,
      cardiac index 2.1 (0.5) l/min/m2, and pulmonary vascular resistance (PVR) 29 (10)
      U/m2. Short-term epoprostenol infusion produced a significant vasodilator
      response in 10 patients (mean fall in PVR 24 (15%) compared with control values).
      Three fenfluramine users with PPH showed spontaneous clinical and haemodynamic
      improvement 3, 6 and 12 months after drug withdrawal but there was no significant
      difference in overall survival (transplant recipients excluded) between
      fenfluramine users and controls. Histological examination of lung tissue from
      five women who had used fenfluramine and 22 controls, with PPH showed features
      typical of advanced plexogenic pulmonary arteriopathy in all. These results do
      not accord with earlier reports that PPH associated with fenfluramine is less
      severe and has a better outcome. Fenfluramine may be one aetiological agent that
      can precipitate or hasten the development of PPH. The results of a European case
      control study should give new insights into risk factors for PPH and the cause
      and effect relation with fenfluramine.

PMID- 8280520
TI  - Role of balloon dilatation of the aortic valve in pregnant patients with severe
      aortic stenosis.
AB  - The outcome of unrelieved severe symptomatic aortic stenosis in pregnancy is
      poor. Though the valve lesion can be corrected surgically before delivery at a
      low risk to the mother, cardiopulmonary bypass during pregnancy carries a high
      risk to the fetus. Two patients in the second trimester of pregnancy were
      successfully managed with balloon dilatation of the aortic valve. Both delivered
      healthy infants and were well a year later. Balloon dilatation of the aortic
      valve is a useful palliative procedure in the management of pregnant women with
      severe aortic stenosis.